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Yue He,1,* Qianhan Liu,1,* Yurong Zheng,1 Shengdan Liu,1 Mingling Yu,1 Changhe Ren,2 Guangxiang Chen1 1Department of Radiology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Department of Pain, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changhe Ren, Department of Pain, Affiliated Hospital of Southwest Medical University, No. 23 Tai Ping Street, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86 18982784626, Email riverrch@163.com Guangxiang Chen, Department of Radiology, Affiliated Hospital of Southwest Medical University, No. 23 Tai Ping Street, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86 18982409881, Email cgx23ly2002@163.comPurpose: Zoster-associated pain (ZAP) is frequently concomitant with psychiatric comorbidities. However, the underlying neuropathological mechanisms of ZAP with psychiatric comorbidities remain poorly understood.Patients and Methods: Rest-stating functional MRI (rs-fMRI) data from 41 ZAP patients without anxiety or depression (noA/D-ZAP), 11 ZAP patients with anxiety or depression (A/D-ZAP) and 29 healthy controls (HCs) were acquired. Degree centrality (DC) based on rs-fMRI was used to explore the node changes in the brain functional network in these subjects. Moreover, correlations and receiver operating characteristic curve analysis were performed.Results: One-way analysis of variance revealed abnormal DC values in the right middle frontal gyrus (MFG) and bilateral precuneus among the three groups. Compared with HCs, A/D-ZAP showed increased DC values in the bilateral pons, while noA/D-ZAP showed increased DC values in the right pons, left brainstem and rectal gyrus and decreased DC values in the right cingulate gyrus and bilateral precuneus. A/D-ZAP showed increased DC values in the left MFG and precentral gyrus (PG) compared with noA/D-ZAP. The DC value of the left pons in A/D-ZAP was positively correlated with the self-rating anxiety scale score. Areas under the curve of DC values in the left PG and MFG for distinguishing A/D-ZAP from the noA/D-ZAP group were 0.907 and 1.000, respectively.Conclusion: This study revealed the node differences in the brain functional network of ZAP patients with or without psychiatric comorbidities. In particular, abnormal DC values of the left MFG and PG may play an important role in the neuropathologic mechanism of the disease.Keywords: functional MRI, degree centrality, zoster-associated pain, anxiety, depression

Yan-Jun Xiong,* Yu Xiao,* Lei Xie, Lei Gao, Yi Han, Peng-Fei Huang, Shuang Liu, Ya-Xue Liang, Hua Wang Department of Tuberculosis, Anhui Provincial Chest Hospital (Anhui Institute of Tuberculosis Control), Hefei, Anhui, 230022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hua Wang, Department of Tuberculosis, Anhui Provincial Chest Hospital (Anhui Institute of Tuberculosis Control), No. 392, Jixi Road, Hefei, Anhui, People’s Republic of China, Tel +86 13395694530, Email 1726553540@qq.comBackground: Linezolid (LZD) is a cornerstone medication in the treatment of drug-resistant tuberculosis (DR-TB). However, it frequently triggers adverse effects such as bone marrow suppression, optic neuropathy, and peripheral neuropathy, all of which can impact treatment outcomes and prognosis. Contezolid (CZD), a novel oxazolidinone antibiotic, exhibits comparable antimicrobial efficacy against Mycobacterium tuberculosis as LZD, but with potentially enhanced safety profiles.Case Presentation: This report presents five cases (Cases 1– 5) of LZD intolerance, wherein CZD served as an effective alternative treatment. In Cases 1– 3, LZD administration resulted in bone marrow suppression, primarily manifested as anemia. Transitioning to CZD therapy led to a rise and stabilization of hemoglobin (HGB) levels in Cases 1– 2, and a return to baseline values in Case 3. In Case 4, CZD treatment alleviated symptoms of LZD-induced peripheral neuritis, although complete resolution was not achieved, hinting at potential irreversibility of this type of peripheral neuropathy. In Case 5, direct CZD anti-TB therapy was initiated for recurrent leukopenia and neutropenia, resulting in no further severe myelosuppression and successful recovery.Conclusion: These case studies suggest that CZD could represent an effective and safe option for anti-TB therapy, especially for patients intolerant to LZD.Keywords: contezolid, linezolid, drug-resistant tuberculosis, myelosuppression, peripheral neuropathy

Liming Qin,1,2,&ast; Moqin Qiu,3,&ast; Jingmei Tang,2 Shuyan Liu,4 Qiuling Lin,5 Qiongguang Huang,2 Xiaoxia Wei,5 Qiuping Wen,1 Peiqin Chen,6 Zihan Zhou,7 Ji Cao,7 Xiumei Liang,8 Qian Guo,9 Cunli Nong,9 Yizhen Gong,5 Yuying Wei,1 Yanji Jiang,10 Hongping Yu,1,2,11– 13 Yingchun Liu1 1Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2School of Public Health, Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Respiratory Oncology, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 4Key Laboratory of Biological Molecular Medicine Research, Education Department of Guangxi Zhuang Autonomous Region, Guangxi Medical University, Nanning, People’s Republic of China; 5Department of Clinical Research, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 6Editorial Department of Chinese Journal of Oncology Prevention and Treatment, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 7Department of Cancer Prevention and Control, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 8Department of Disease Process Management, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 9Liuzhou Worker’s Hospital, Liuzhou, People’s Republic of China; 10Department of Scientific Research, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 11Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Guangxi Medical University, Nanning, People’s Republic of China; 12Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, People’s Republic of China; 13Key Cultivated Laboratory of Cancer Molecular Medicine of Guangxi Health Commission, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingchun Liu; Hongping Yu, Department of Experimental Research, Guangxi Medical University Cancer Hospital, 71&num; Hedi Road, Qingxiu District, Nanning, People’s Republic of China, Tel +86-15877191237 ; +86-771-5330850, Fax +86-771-5312000, Email liuyingchun@stu.gxmu.edu.cn; yuhongping@stu.gxmu.edu.cnPurpose: P53 is a suppressor gene closely related to carcinogenesis. However, the associations between genetic variants in the p53 signaling pathway and prognosis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unknown. The current study aims to analyze associations between the single nucleotide polymorphisms (SNPs) in p53 pathway-related genes and survival of patients with HBV-HCC.Methods: We evaluated the associations between 4698 SNPs in 70 genes of the p53 pathway and overall survival (OS) of 866 patients in additive genetic models by using Cox proportional hazards regression analysis. Stepwise multivariable Cox regression analysis was conducted to determine the independent effects of identified SNPs in single-locus analyses. The expression of quantitative trait loci (eQTL) was also analyzed using data from GTEx and 1000 Genomes Project, and functional prediction of SNPs was performed by using RegulomeDB v2.2, 3DSNP v2.0, HaploReg v4.2 and VannoPortal.Results: We found that two novel SNPs of CD82 rs7925603 A > G and PMAIP1 rs4396625 A > T, were significantly and independently associated with OS [adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were 1.27 (1.10– 1.48) and 0.77 (0.66– 0.91), respectively; P = 0.001 and = 0.002, respectively] and that the combined risk genotypes of these SNPs showed a significant association with OS in patients with HBV-HCC (Ptrend < 0.001). Further eQTL analysis in the GTEx dataset showed that the rs7925603 G allele was associated with lower CD82 mRNA expression levels, while the rs4396625 T allele was associated with higher PMAIP1 mRNA expression levels in whole blood cells.Conclusion: We identified two observed survival-associated SNPs in CD82 and PMAIP1 in the p53 pathway, which influenced HBV-HCC survival possibly through a mechanism of altering mRNA expression. Large studies are warranted to validate our findings.Keywords: hepatocellular carcinoma, hepatitis B virus, p53 signaling pathway, genetic variants, survival

Fujie Jiang,1,&ast; Shuling Liu,1,&ast; Lu Wang,1 Huifang Chen,1 Yao Huang,2 Ying Cao,2 Xiaoxia Wang,1 Meng Lin,1 Jiuquan Zhang1 1Department of Radiology, Chongqing University Cancer Hospital, Chongqing Key Laboratory for Intelligent Oncology in Breast Cancer (iCQBC), Chongqing, 400030, People’s Republic of China; 2School of Medicine, Chongqing University, Chongqing, 400030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiuquan Zhang; Meng Lin, Department of Radiology Chongqing University Cancer Hospital, No. 181 Hanyu Road, Shapingba District, Chongqing, 400030, People’s Republic of China, Tel/Fax +86-23-65079339, Email zhangjq_radiol@foxmail.com; 15823113338@139.comPurpose: Chemotherapy mediated by Reactive oxygen species (ROS)-responsive drug delivery systems can potentially mitigate the toxic side effects of chemotherapeutic drugs and significantly enhance their therapeutic efficacy. However, achieving precise targeted drug delivery and real-time control of ROS-responsive drug release at tumor sites remains a formidable challenge. Therefore, this study aimed to describe a ROS-responsive drug delivery system with specific tumor targeting capabilities for mitigating chemotherapy-induced toxicity while enhancing therapeutic efficacy under guidance of Fluorescence (FL) and Magnetic resonance (MR) bimodal imaging.Methods: Indocyanine green (ICG), Doxorubicin (DOX) prodrug pB-DOX and Superparamagnetic iron oxide (SPIO, Fe3O4) were encapsulated in poly(lactic-co-glycolic acid) (PLGA) by double emulsification method to prepare ICG/ pB-DOX/ Fe3O4/ PLGA nanoparticles (IBFP NPs). The surface of IBFP NPs was functionalized with mammaglobin antibodies (mAbs) by carbodiimide method to construct the breast cancer-targeting mAbs/ IBFP NPs (MIBFP NPs). Thereafter, FL and MR bimodal imaging ability of MIBFP NPs was evaluated in vitro and in vivo. Finally, the combined photodynamic therapy (PDT) and chemotherapy efficacy evaluation based on MIBFP NPs was studied.Results: The multifunctional MIBFP NPs exhibited significant targeting efficacy for breast cancer. FL and MR bimodal imaging clearly displayed the distribution of the targeting MIBFP NPs in vivo. Upon near-infrared laser irradiation, the MIBFP NPs loaded with ICG effectively generated ROS for PDT, enabling precise tumor ablation. Simultaneously, it triggered activation of the pB-DOX by cleaving its sensitive moiety, thereby restoring DOX activity and achieving ROS-responsive targeted chemotherapy. Furthermore, the MIBFP NPs combined PDT and chemotherapy to enhance the efficiency of tumor ablation under guidance of bimodal imaging.Conclusion: MIBFP NPs constitute a novel dual-modality imaging-guided drug delivery system for targeted breast cancer therapy and offer precise and controlled combined treatment options.Keywords: targeted drug delivery, photodynamic therapy, ROS-responsive chemotherapy, bimodal imaging

Chao Meng,1 Ping Yang,2 Yanan Wang,3 Siyan Liu,3 Xueyan Wu,3 Shaolian Wang3 1Department of General Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Department of Integrated Chinese and Western Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 3Department of Endocrinology, Central Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of ChinaCorrespondence: Shaolian Wang, Email 15318816221@sina.cnBackground: To investigate the prevalence of thyroid nodules among medical staff and health check-up population in a Level-A hospital (Primary-level hospital) in Jinan City and analyze its influencing factors.Methods: A total of 5812 cases from the two groups were screened. t-test and χ2 tests were used to analyze the differences in the prevalence of thyroid nodules. Multivariate Logistic regression analysis was used to explore the influencing factors.Results: The average age of medical staff was (36.20± 9.11) years old, and the total prevalence was 48.5%. The average age of the healthcare population was (57.89± 12.51) years old, and the total prevalence rate was 63.9%, with statistical significance between the two groups (P

Licai Miao,1,&ast; Zihao Xu,1,&ast; Junhao Sui,1,&ast; Xiangyu Meng,1,&ast; Shicheng Huo,2 Shu Liu,1 Mengchen Chen,1 Zhong Zheng,1 Xiaobin Cai,3 Hao Zhang1 1Department of Orthopedics, Changhai Hospital Affiliated to the Navy Military Medical University, Shanghai, 200433, People’s Republic of China; 2Department of Orthopedic Surgery, Spine Center, Changzheng Hospital, Navy Medical University, Shanghai, 200003, People’s Republic of China; 3Department of Orthopedics Shanghai Tenth People’s Hospital Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaobin Cai, Department of Orthopedics Shanghai Tenth People’s Hospital Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China, Tel +8613122575295, Email caixbjn@163.com Hao Zhang Department of Orthopedics, Changhai Hospital Affiliated to the Navy Military Medical University, Tel +8613917856377, Email zhanghsmmu@126.comPurpose: Skin injury, often caused by physical or medical mishaps, presents a significant challenge as wound healing is critical to restore skin integrity and tissue function. However, external factors such as infection and inflammation can hinder wound healing, highlighting the importance of developing biomaterials with antibiotic and wound healing properties to treat infections and inflammation. In this study, a novel photothermal nanomaterial (MMPI) was synthesized for infected wound healing by loading indocyanine green (ICG) on magnesium-incorporated mesoporous bioactive glass (Mg-MBG) and coating its surface with polydopamine (PDA).Results: In this study, Mg-MBG and MMPI was synthesized via the sol-gel method and characterized it using various techniques such as scanning electron microscopy (SEM), the energy dispersive X-ray spectrometry (EDS) system and X-ray diffraction (XRD). The cytocompatibility of MMPI was evaluated by confocal laser scanning microscopy (CLSM), CCK8 assay, live/dead staining and F-actin staining of the cytoskeleton. The antibacterial efficiency was assessed using bacterial dead-acting staining, spread plate method (SPM) and TEM. The impact of MMPI on macrophage polarization was initially evaluated through flow cytometry, qPCR and ELISA. Additionally, an in vivo experiment was performed on a mouse model with skin excision infected. Histological analysis and RNA-seq analysis were utilized to analyze the in vivo wound healing and immunomodulation effect.Conclusion: Collectively, the new photothermal and photodynamic nanomaterial (MMPI) can achieve low-temperature antibacterial activity while accelerating wound healing, holds broad application prospects.Keywords: infection-related wounds, magnesium-doped bioactive glass, photothermal therapy, photodynamic therapy, immunomodulation

Simin Liu,1,&ast; Zhiyuan Tian,2 Taiming Zhang,3 Jirong Zhang,3 Yanlei Huo,1,&ast; Chao Ma1 1Department of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Nuclear Medicine, Zibo Ninth People’s Hospital, Zibo, Shandong, People’s Republic of China; 3Department of Medical Imaging, People’s Hospital of Shuangjiang Autonomous Country, Lincang, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Ma, Department of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University, Yanchangzhong Road 301, Shanghai, 200072, People’s Republic of China, Tel +86 21-66302075, Email mc_7419@hotmail.comObjective: To explore analgesic effect and bone repair mechanism of non-radioactive technetium-99 conjugated with methylene diphosphonate (99Tc-MDP, brand name, Yunke) on bone metastases (BM).Procedures: In vivo experiment, mouse BM models of prostate cancer RM-1 cell were constructed and divided into Control, Yunke, 99Tc+SnCl2 and MDP groups based on medicine composition. Tumor specimens were inspected for size, X-ray, microCT and histopathology. In vitro experiment, with Cell Counting Kit-8 (CCK8), scratch, clone, apoptosis, Polymerase Chain Reaction (PCR) and Western Blot experiments, effects of Yunke on RM-1 cells and osteoclast-related cells were observed.Results: In vivo experiment, there was no difference in tumor size between Yunke and control group. Contrasted with control group, in Yunke group, trabecular spacing (Tb.Sp) of tumor bone was lower, bone volume/total volume (BV/TV) on marrow cavity and bone cortex were higher. Tunnel staining showed that positive rate of apoptosis in Yunke group was higher than that in control group. Ki67 staining showed that Yunke could not inhibit proliferation of tumor cells. In vitro experiment, CCK8 and scratch experiments showed that Yunke neither can inhibit proliferation nor can inhibit migration of RM-1 cells. High concentration of Yunke promoted late apoptosis of RM-1 cells. Yunke could inhibit BMM cell proliferation, differentiation of osteoclasts, and osteoclast-related transcription factors. Yunke displayed different degrees of inhibitory effects on MAPKs signaling pathway during osteoclast differentiation. It had obvious inhibitory effects on osteoclast-related transcription factors, such as cFOS, NFATC1, ACP-5, CTSK, D2 and MMP-9, the strongest inhibitory effects were observed with ACP-5, CTSK and D2. Yunke also displayed different degrees of inhibitory effects on protein activities of JNK, pERK, ERK and pP38.Conclusion: Yunke cannot inhibit the proliferation and migration of RM-1 cells, so we think it is not recommended for the treatment of primary tumors and prevention of occurrence of tumors metastatic to bones. The mechanism of therapeutic effect of Yunke on BM by inhibiting proliferation of BMM, inhibiting MAPKs signal transduction and activation of transcription factors during differentiation process of BMM-derived osteoclasts, inhibiting number and size of osteoclasts, inhibiting bone resorption and protecting bone destruction through enhancing bone hardness and bone mass. Thereby, we believe that Yunke is more suitable for promoting the repair induced by BMs, delaying its progression and reducing the occurrence of SREs.Keywords: 99Tc-MDP, bone metastases, molecular mechanisms, RM-1, prostate cancer

Lei Liu,1,&ast; Shanshan Liu,2,&ast; Fuyan Bai,1 Yangxin Deng,1 Xinhuan Zhang,1 Li Wang3 1Department of Endocrinology, the Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, People’s Republic of China; 2General Gynecology, the Tai ‘an Central Hospital, Taian, Shandong, People’s Republic of China; 3Department of Pharmacy, the Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinhuan Zhang; Li Wang, Email zhangxh22009@126.com; suxinlan1027@126.comBackground: An important factor in the pathogenesis of polycystic ovary syndrome (PCOS) is chronic low-grade inflammation. However, the exact pathophysiology of PCOS is currently unknown, which makes clinical diagnosis and the development of effective treatments more difficult. We aimed to investigate the role of the inflammatory response in initiating and progressing PCOS.Methods: 13 control granulosa cell samples and 15 granulosa cell samples from patients with PCOS were obtained from the GSE102293, GSE34526, and GSE5850 datasets. The gene set variation analysis (GSVA) method was used to calculate the inflammatory response score. Subsequently, the genes associated with inflammation in the hub were identified using differential expression analysis and weighted gene co-expression network analysis (WGCNA). The findings were confirmed by analysis of independent datasets and examination of clinical samples by qRT-PCR analysis. A consensus cluster analysis was conducted to categorize the PCOS samples into subtypes related to inflammation. Functional enrichment and analysis of immune cell infiltration were conducted to explore the potential mechanisms involved. Additionally, the CMap database was utilized to predict potential drugs, and the results were confirmed through molecular docking.Results: During the training cohort analysis, we identified five distinct genes (TGFBR2, ICAM3, WIPF1, SLC11A1, and NCF2) that could serve as potential diagnostic markers for PCOS. The expression levels of these genes were confirmed through validation in both the test set and clinical samples. In training cohort, two distinct inflammatory patterns (C1 and C2) were identified, and the C2 subtype exhibited activated immune- and inflammation-related pathways. Esmolol was shown to have potential as a drug to treat PCOS and it showed good results for molecular binding at TGFBR2, ICAM3, WIPF1, SLC11A1, and NCF2 proteins.Conclusion: Five diagnostic biomarkers and two inflammation-related molecular types associated with PCOS were identified, and esmolol was a potential drug for PCOS treatment. Our findings provided new diagnostic markers and potential small-molecule drugs for PCOS diagnosis and prevention.Keywords: polycystic ovary syndrome, inflammatory response, diagnostic biomarkers, molecular subtypes, esmolol

Bin Hu,1 Jingchun Pei,1 Cheng Wan,1,2 Shuangshuang Liu,1 Zhe Xu,3,4 Yongwei Zou,1 Zhigao Li,1 Zhiwei Tang1 1Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 2Department of Medical Imaging, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Kunming, People’s Republic of China; 4School of Basic Medical Sciences, Qujing Medical College, Qujing, People’s Republic of ChinaCorrespondence: Zhiwei Tang, Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650032, People’s Republic of China, Email tangzhiwei7755@hotmail.comAbstract: Ischemic stroke constitutes a significant global health care challenge, and a comprehensive understanding of its recovery mechanisms is imperative for the development of innovative therapeutic strategies. Angiogenesis, a pivotal element of ischemic tissue repair, facilitates the restoration of blood flow to damaged regions, thereby promoting neuronal regeneration and functional recovery. Nevertheless, the mechanisms underlying postischemic stroke angiogenesis remain incompletely elucidated. This review meticulously examines the constituents of the neurovascular unit, ion channels, molecular mediators, and signaling pathways implicated in angiogenesis following stroke. Furthermore, it delves into prospective therapeutic strategies informed by these factors. Our objective is to provide detailed and exhaustive information on the intricate mechanisms governing postischemic stroke angiogenesis, thus providing a robust scientific foundation for the advancement of novel neurorepair therapies.Keywords: ischemic stroke, angiogenesis, signaling pathways

Wenze Han,1,2 Ran Zhang,1,2 Shuzhi Liu,1,2 Tong Zhang,1,2 Xuemin Yao,1,2 Yuxin Cao,1,2 Jiadi Li,1,2 Xiaoming Liu,1,2 Bing Li1,2 1Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, 030001, People’s Republic of China; 2Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, People’s Republic of ChinaCorrespondence: Xiaoming Liu; Bing Li, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, 030001, People’s Republic of China, Email lxming0912@163.com; libing1975vip@163.comAbstract: Whiskers are nanoscale, high-strength fibrous crystals with a wide range of potential applications in dentistry owing to their unique mechanical, thermal, electrical, and biological properties. They possess high strength, a high modulus of elasticity and good biocompatibility. Hence, adding these crystals to dental composites as reinforcement can considerably improve the mechanical properties and durability of restorations. Additionally, whiskers are involved in inducing the value-added differentiation of osteoblasts, odontogenic osteocytes, and pulp stem cells, and promoting the regeneration of alveolar bone, periodontal tissue, and pulp tissue. They can also enhance the mucosal barrier function, inhibit the proliferation of tumor cells, control inflammation, and aid in cancer prevention. This review comprehensively summarizes the classification, properties, growth mechanisms and preparation methods of whiskers and focuses on their application in dentistry. Due to their unique physicochemical properties, excellent biological properties, and nanoscale characteristics, whiskers show great potential for application in bone, periodontal, and pulp tissue regeneration. Additionally, they can be used to prevent and treat oral cancer and improve medical devices, thus making them a promising new material in dentistry.Keywords: whiskers, dentistry, growth mechanism, biomaterials

Sijia Liu,1,2,&ast; Ting Yang,1,2,&ast; Qingsong Jiang,1,2 Liang Zhang,1,2 Xinhui Shi,1,2 Xin Liu,3 Xiaoli Li1,2 1Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China; 2Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, People’s Republic of China; 3Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoli Li; Xin Liu, Email lixiaoli@cqmu.edu.cn; liux0704@tmmu.edu.cnAbstract: Sepsis is a disorder of the immune response to infection or infectious factors with high morbidity and mortality in clinical settings. The lactylation of lysine residues, fueled by lactate, plays a pivotal role in its pathophysiology. In conducting a literature review on sepsis-related research, we employed a systematic approach to ensure comprehensiveness and accuracy. Initially, we conducted an extensive literature search through the PubMed database, utilizing a range of keywords including “sepsis”, “lactate”, “lactylation”, and “epigenetic modification”. The aim was to capture the most recent research related to the pathophysiological mechanisms of sepsis, metabolic disorders, and the role of lactylation. The results of the literature review revealed a close link between sepsis and metabolic dysfunction, particularly the pivotal role of lactylation in regulating immune responses and inflammatory processes. Lactate, not only an energy metabolic byproduct produced during glycolysis, affects the activity of various proteins, including those involved in immune regulation and cell signaling, through lactylation. In the context of sepsis, changes in the levels of lactylation may be closely associated with the severity and prognosis of the disease. In summary, lactylation, as an emerging type of epigenetic modification, provides a new perspective for the diagnosis and treatment of sepsis. Future research needs to further elucidate the exact mechanisms of lactylation in sepsis and explore its potential as a therapeutic target.Plain Language Summary: The annual incidence and mortality rates associated with sepsis are on the rise, and to date, no medications or therapies have been proven effective in clinical practice. Glycolysis plays a pivotal role in regulating lactylation, a process derived from lactate generated by cellular glucose metabolism. In the context of sepsis, elevated lactate levels are indicative of a poor prognosis. It is imperative to delve into the mechanisms underlying lactylation alterations during sepsis to enhance our comprehension of its complex pathophysiology and to pinpoint innovative therapeutic targets for the condition. Keywords: sepsis, lactate, lactylation, epigenetic modification

Yuwei Jiang,1,2,&ast; Wenjun Dang,3,&ast; Lirong Sui,1 Tianci Gao,1 Xiangying Kong,1 Jin Guo,1 Shuang Liu,1 Hong Nie,3 Zhimei Jiang1,2 1College of Rehabilitation Medicine, Jiamusi University, Jiamusi City, Hei longJiang Province, People’s Republic of China; 2Pediatric Cerebral Palsy Prevention and Treatment Center of Heilongjiang Province, Jiamusi City, Hei longJiang Province, People’s Republic of China; 3College of Jiamusi, HeiLongJiang University of Chinese Medicine, Jiamusi City, Hei longJiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhimei Jiang; Shuang Liu, Email 15704601990@163.com; 307692456@qq.comAbstract: We conducted an umbrella evaluation to quantitatively synthesize previous systematic reviews and meta-analyses, thereby collating evidence on the association between vitamin D and core symptoms in people with autism in anticipation of informing clinical vitamin D supplementation. Based on the pre-established protocol, we ended up with 9 studies. Based on rigorous analysis, we found that vitamin D deficiency early in life is a risk factor for the development of ASD and that vitamin D supplementation improves the core symptoms of ASD. Our study concludes that vitamin D supplementation is beneficial for individuals with autism, that vitamin D deficiency early in embryonic life increases the risk of ASD, and that our study supports the idea that prevention begins with vitamin D supplementation early in life. At the same time, we must recognize that our current conclusions support the benefits of vitamin D supplementation for children with ASD, but we are unable to determine the causal relationship, ie, how vitamin D works in ASD, and we need more basic research to explore the mechanisms involved.Keywords: autism spectrum disorders, vitamin D, core symptoms, 25(OH)D, umbrella review

Fan Zhao,1,2 Jitong Wang,1,2 Yu Zhang,1,2 Jinru Hu,1,2 Chenyang Li,3 Shuainan Liu,4,5 Ruixiang Li,2 Ruofei Du1,2 1Engineering Research Center of Modern Preparation Technology of TCM, Ministry of Education, Shanghai, 201203, People’s Republic of China; 2Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, 518055, People’s Republic of China; 4State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Key Laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, People’s Republic of China; 5Diabetes Research Center of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Ruixiang Li, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China, Email ruixiangli@shutcm.edu.cn Ruofei Du, Engineering Research Center of Modern Preparation Technology of TCM, Ministry of Education, Shanghai, 201203, People’s Republic of China, Email drf790101@shutcm.edu.cnAbstract: This review aimed to systematically investigate the intracellular and subcellular fate of various types of targeting carriers. Upon entering the body via intravenous injection or other routes, a targeting carrier that can deliver therapeutic agents initiates their journey. If administered intravenously, the carrier initially faces challenges presented by the blood circulation before reaching specific tissues and interacting with cells within the tissue. At the subcellular level, the car2rier undergoes processes, such as drug release, degradation, and metabolism, through specific pathways. While studies on the fate of 13 types of carriers have been relatively conclusive, these studies are incomplete and lack a comprehensive analysis. Furthermore, there are still carriers whose fate remains unclear, underscoring the need for continuous research. This study highlights the importance of comprehending the in vivo and intracellular fate of targeting carriers and provides valuable insights into the operational mechanisms of different carriers within the body. By doing so, researchers can effectively select appropriate carriers and enhance the successful clinical translation of new formulations.Plain language summary: Nowadays, scientists are actively researching nanocarrier drugs. After administration via injection or other methods, these drugs experience in the body and reach the target treatment site to relieve or cure symptoms. As research progresses, scientists are gaining more insights into the behavior of nanocarrier drugs in the body, which is useful in developing safer and more effective drugs. Historically, research has focused primarily on the drug itself. However, it is important to understand that the carrier that delivers and protects the drug (often described as the drug sitting in a “car” or under an “umbrella”) plays an essential role in the drug’s therapeutic effect. This paper aims to highlight the importance of the carrier’s role, which is vital for developing new drugs and advancing basic research. Keywords: drug carriers, targeted delivery, in vivo fate, subcellular fate

Yuan Zhuang,1,2 Ru Zhang,3,4 Miaomiao Li,3,4 Yaru Zou,1 Shui Jiang,1 Yanan Zhang,1 Shiguo Liu,3,4 Bo Yu1 1Dermatological Department, The Affiliated Hospital of QingdaoUniversity, Qingdao, People’s Republic of China; 2dermatological department, Women and Children’s hospital, Qingdao University, Qingdao, People’s Republic of China; 3Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 4Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Bo Yu, Dermatological department, The Affiliated Hospital of QingdaoUniversity, Qingdao, People’s Republic of China, Email yubo@qduhospital.cn Shiguo Liu, Medical Genetic Department, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Email liushiguo@qdu.edu.cnIntroduction: Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder that influences structures of ectodermal origin, such as teeth, hair, and sweat glands. Compared with autosomal recessive and dominant modes of inheritance, the X-linked HED (XLHED) characterized by Hypodontia/Oligodontia teeth, Absent/sparse hair, Anhidrosis/hypohidrosis, and characteristic facial features, is the most frequent and its primary cause is the mutation of ectodysplasin A (EDA) gene. This research aimed to expound the clinical and molecular features of a Chinese male with XLHED and to summarize and compare several previous findings.Methods: Genomic DNA was obtained from the peripheral blood of the proband and his family members, then Sanger sequencing was used to perform a mutational analysis of EDA. Real-time quantitative PCR and Western blotting were used to detect EDA expression. The transcriptional activity of NF-κB was detected using a luciferase assay.Results: The probandwith XLHED was identified a novel EDA mutation, c.1119G>C(p.M373I), that affected the molecular analysis of transmembrane protein exon8 mutations, inherited from the mother. He showed a severe multiple-tooth loss, with over 20 permanent teeth missing and sparse hair and eyebrows, dry, thin, and itching skin. Furthermore, his sweating function was abnormal to a certain extent.Discussion: The functional study showed that this novel mutant led to a significant decrease in the EDA expression level and transcriptional activity of NF-κB. Our findings extend the range of EDA mutations in XLHED patients, which provides the basis and idea for further exploring the pathogenesis of XLHED.Keywords: EDA, X-linked hypohidrotic ectodermal dysplasia, gene mutation

Shuangjin Liu, Zihao Zeng, Qi Qi, Qin Yang, Yiqiu Hu School of Educational Science, Hunan Normal University, Changsha, 410006, People’s Republic of ChinaCorrespondence: Yiqiu Hu, School of Educational Science, Hunan Normal University, Changsha, 410006, People’s Republic of China, Email fortune2000947@163.comBackground: Based on the gene-environment interaction paradigm, this study explored the effect of peer relationships on adolescent loneliness and the role of psychological resilience and the oxytocin receptor gene (OXTR).Methods: A survey was conducted in a sample of 619 adolescents, and their oral cells were collected for DNA extraction and genotyping.Results: The results showed that (1) both peer relationships and psychological resilience significantly affected adolescent loneliness; (2) psychological resilience partially mediated the relationship between peer relationships and loneliness in adolescents; (3) OXTR gene rs53576 polymorphism moderated both the first and second half of the indirect pathway of the mediation model. Specifically, carriers of the rs53576 polymorphism A/A genotype showed a significantly enhanced effect of peer relationships on adolescent psychological resilience, while carriers of the rs53576 polymorphism G/G genotype showed a significantly enhanced effect of psychological resilience on adolescent loneliness.Conclusion: These findings helped elucidate the developmental mechanisms of adolescent loneliness in terms of peer relationships, psychological resilience, and OXTR gene polymorphisms.Plain Language Summary: A moderated mediation effects analysis was conducted to investigate the effect of peer relationships on adolescent loneliness and the role of psychological resilience and the oxytocin receptor gene (OXTR). The results revealed psychological resilience partially mediated the relationship between peer relationships and loneliness in adolescents; OXTR gene rs53576 polymorphism moderated both the first and second half of the indirect pathway of the mediation model. These findings helped elucidate the developmental mechanisms of adolescent loneliness in terms of peer relationships, psychological resilience, and OXTR gene polymorphisms.Keywords: peer relationship, adolescents, loneliness, psychological resilience, OXTR gene

Qianfeng Li,1,&ast; Bo Wang,2,&ast; Jun Yang,3 Yuan Wang,1 Faliang Duan,1 Ming Luo,1 Chungang Zhao,4 Wei Wei,2 Lei Wang,3 Sha Liu2,5 1Department of Neurosurgery, Wuhan No.1 Hospital, Wuhan, People’s Republic of China; 2Brain Research Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Huanggang Central Hospital of Yangtze University, Huanggang, People’s Republic of China; 4Jilin Jianda Modern Agricultural Research Institute, Changchun, People’s Republic of China; 5Department of General Practice, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Wang; Sha Liu, Email wanglei@hgyy.org.cn; sha.liu@whu.edu.cnBackground: Aging is recognized as the key risk for intracerebral hemorrhage (ICH). The detailed mechanisms of aging in ICH warrant exploration. This study aimed to identify potential aging-related genes associated with ICH.Methods: ICH-specific aging-related genes were determined by the intersection of differentially expressed genes (DEGs) between perihematomal tissues and corresponding contralateral parts of four patients with ICH (GSE24265) and 349 aging-related genes obtained from the Aging Atlas database. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) analyses were performed to identify the potential biological functions and pathways in which these ICH-specific aging-related genes may be involved. Then, PPI network was established to identify the hub genes of ICH-specific aging-related genes. Meanwhile, miRNA-mRNA and transcription factor (TF)-mRNA regulatory networks were constructed to further explore the ICH-specific aging-related genes regulation. The relationship between these hub genes and immune infiltration was also further explored. Additional single-cell RNA-seq analysis (scRNA-seq, GSE167593) was used to locate the hub genes in different cell types. Besides, expression levels of the hub genes were validated using clinical samples from our institute and another GEO dataset (GSE206971).Results: This study identified 24 ICH-specific aging-related genes, including 22 up-regulated and 2 down-regulated genes. The results of GO and KEGG suggested that the ICH-specific aging-related genes mainly enriched in immunity and inflammation-related pathways, suggesting that aging may affect the ich pathogenesis by regulating inflammatory and immune-related pathways.Conclusion: Our study revealed 24 ICH-specific aging-related genes and their functions highly pertinent to ICH pathogenesis, providing new insights into the impact of aging on ICH.Keywords: intracerebral hemorrhage, aging, immune infiltration, single-cell RNA sequencing, molecular docking

Ying Wang,1,&ast; Yiyan Xu,2,&ast; Jiayu Song,1 Xueting Liu,1 Sijia Liu,1 Nan Yang,1 Le Wang,1 Yujie Liu,1 Yiwei Zhao,1 Wenhu Zhou,3,4 Yunyan Zhang1 1Department of Gynecological Radiotherapy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Department of Vascular Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, People’s Republic of China; 3Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 4Hunan Key Laboratory of The Research and Development of Novel Pharmaceutical Preparations, School of Pharmaceutical Science, Changsha Medical University, Changsha, 410219, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunyan Zhang, Department of Gynecological Radiotherapy, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, Heilongjiang Province, 150081, People’s Republic of China, Tel +86 13604843878, Fax +86 451 85718392, Email zhangyunyan@hrbmu.edu.cn Wenhu Zhou, Xiangya School of Pharmaceutical Sciences, Central South University, 172 Tongzipo Road, Changsha, Hunan, 410013, People’s Republic of China, Tel +86 15111469284, Fax +86 731 88710591, Email zhouwenhuyaoji@163.comPurpose: Phototherapy, known for its high selectivity, few side effects, strong controllability, and synergistic enhancement of combined treatments, is widely used in treating diseases like cervical cancer.Methods: In this study, hollow mesoporous manganese dioxide was used as a carrier to construct positively charged, poly(allylamine hydrochloride)–modified nanoparticles (NPs). The NP was efficiently loaded with the photosensitizer indocyanine green (ICG) via the addition of hydrogen phosphate ions to produce a counterion aggregation effect. HeLa cell membrane encapsulation was performed to achieve the final M-HMnO2@ICG NP. In this structure, the HMnO2 carrier responsively degrades to release ICG in the tumor microenvironment, self-generates O2 for sensitization to ICG-mediated photodynamic therapy (PDT), and consumes GSH to expand the oxidative stress therapeutic effect [chemodynamic therapy (CDT) + PDT]. The ICG accumulated in tumor tissues exerts a synergistic PDT/photothermal therapy (PTT) effect through single laser irradiation, improving efficiency and reducing side effects. The cell membrane encapsulation increases nanomedicine accumulation in tumor tissues and confers an immune evasion ability. In addition, high local temperatures induced by PTT can enhance CDT. These properties of the NP enable full achievement of PTT/PDT/CDT and targeted effects.Results: Mn2+ can serve as a magnetic resonance imaging agent to guide therapy, and ICG can be used for photothermal and fluorescence imaging. After its intravenous injection, M-HMnO2@ICG accumulated effectively at mouse tumor sites; the optimal timing of in-vivo laser treatment could be verified by near-infrared fluorescence, magnetic resonance, and photothermal imaging. The M-HMnO2@ICG NPs had the best antitumor effects among treatment groups under near-infrared light conditions, and showed good biocompatibility.Conclusion: In this study, we designed a nano-biomimetic delivery system that improves hypoxia, responds to the tumor microenvironment, and efficiently loads ICG. It provides a new economical and convenient strategy for synergistic phototherapy and CDT for cervical cancer.Keywords: phototherapy, reactive oxygen species, hypoxia relief, collaborative therapy

Sandip Patil,1,2,&ast; Xinye Li,3,&ast; Pai Liu,1 Yan Dai,3 Xiyi Zhu,3 Junjun Li,3 Sixi Liu,1 Feiqiu Wen1,2 1Department of Haematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 2Paediatric Research Institute, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 3Department of Paediatrics, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning City, Guangxi Zhuang Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feiqiu Wen, Department of Haematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, Guangdong, People’s Republic of China, Tel +86-755-83009888, Email fwen62@163.comBackground: Syphilis, a prevalent sexually transmitted infection, poses severe risks, especially during pregnancy. This study aimed to elucidate the trends and impacts of syphilis in Guangxi, China, focusing on prevalence, clinical manifestations, and treatment outcomes in pregnant women and newborns. The objectives included understanding the demographic characteristics of affected pregnant women, analysing the clinical manifestations in newborns, and assessing the effectiveness of the treatment protocol.Methods: Conducted in adherence to ethical guidelines, a retrospective cohort study from January 2013 to December 2023 included 54,048 pregnant women tested for T. pallidum. Diagnosis involved a comprehensive approach, utilizing tests like the Toluidine Red Unheated Serum Test (TRUST) and the Treponema pallidum Particle Agglutination (TPPA) assay. Infant diagnosis and clinical manifestations were evaluated through a decade-long follow-up. Treatment protocols, including Benzathine penicillin, were implemented. Statistical analyses were conducted using SAS version 9.4.Results: Among 54,048 pregnant women, 0.10% were syphilis positive, correlating with a rise in hospitalizations. Newborns exhibited varied clinical manifestations, with neonatal pneumonia and jaundice being prevalent. The treatment protocol, especially with Benzathine penicillin, achieved a remarkable 100% cure success rate. The study noted a significant reduction in mother-to-child transmission. Syphilis in mothers and babies was diagnosed at different clinical stages, including primary, secondary, latent, and tertiary.Conclusion: This study underscores the escalating impact of syphilis on pregnant women and newborns in Guangxi, China. The findings highlight the necessity for robust preventive measures, early diagnosis, and effective treatment strategies. The observed 100% cure success rate with Benzathine penicillin emphasizes the importance of strict treatment protocols in mitigating the adverse effects of congenital syphilis and reducing its transmission.Keywords: congenital syphilis, mother-to-child transmission, diagnosis, antibiotic treatment

Xiuwen Chen,1,&ast; Meiyan Zou,1,&ast; Siquan Liu,1 Weilin Cheng,1 Weihong Guo,2 Xiaoli Feng1 1Stomatology Hospital, School of Stomatology, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of General Surgery, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weihong Guo; Xiaoli Feng, Email drguowh@163.com; dentistfxl226@163.comAbstract: Graphene family nanomaterials (GFNs) have attracted considerable attention in diverse fields from engineering and electronics to biomedical applications because of their distinctive physicochemical properties such as large specific surface area, high mechanical strength, and favorable hydrophilic nature. Moreover, GFNs have demonstrated the ability to create an anti-inflammatory environment and exhibit antibacterial effects. Consequently, these materials hold immense potential in facilitating cell adhesion, proliferation, and differentiation, further promoting the repair and regeneration of various tissues, including bone, nerve, oral, myocardial, and vascular tissues. Note that challenges still persist in current applications, including concerns regarding biosecurity risks, inadequate adhesion performance, and unsuitable degradability as matrix materials. This review provides a comprehensive overview of current advancements in the utilization of GFNs in regenerative medicine, as well as their molecular mechanism and signaling targets in facilitating tissue repair and regeneration. Future research prospects for GFNs, such as potential in promoting ocular tissue regeneration, are also discussed in details. We hope to offer a valuable reference for the clinical application of GFNs in the treatment of bone defects, nerve damage, periodontitis, and atherosclerosis. Keywords: graphene, graphene oxide, regenerative medicine, scaffold, anti-inflammatory, bone regeneration, nerve, angiogenesis, dental pulp stem cells

Yongchao Li,1,&ast; Jinfeng Gao,2,&ast; Shuhua Liu,1 Shijian Chen,3 Xiaoyue Wei,3 Yalun Guan,1 Xuejiao Li,1 Yunfeng Li,1 Zhongqiang Huang,1 Ge Li,1 Yuhong Zhao,3 Pinghua Liu,4 Yu Zhang1 1Guangdong Provincial Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, 510663, People’s Republic of China; 2Guangdong Quality Supervision and Testing Station for Medical and Health Care Appliances, Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou, 510632, People’s Republic of China; 3School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China; 4Department of Chemistry, Boston University, Boston, MA, 02215, USA&ast;These authors contributed equally to this workCorrespondence: Yu Zhang; Pinghua Liu, Email zhangyugzh@hotmail.com; pinghua@bu.eduBackground: Ergothioneine (EGT) is an antioxidant, which could be detected in human tissues, and human skin cells could utilize EGT and play an anti-oxidative role in keratinocytes. And in this study we are going to elucidate whether EGT could protect the skin from photoaging by Ultraviolet (UV) exposure in mice and its molecule pathway.Methods: Histological analysis was performed for evaluating the skin structure change. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured with biological assay for evaluating oxidative and antioxidative ability of skin exposed to UV light. And the level of marker molecules in mouse skin were detected by hydroxyproline (Hyp) assay, immunohistochemical analysis, Western blot, and quantitative real-time PCR (qRT-PCR). The markers of skin aging and cell death were tested by cell culture and treatment, Western blot and qRT-PCR.Results: EGT decreased the levels of inflammatory factors induced by UV exposure in mouse skin. MDA and SOD activity detection showed that EGT decreased MDA levels, increased SOD activity, and upregulated PI3K/Akt/Nrf2 signals in mouse skin exposed to UV, which further activated Nrf2 in the nucleus and enhanced the expression of Nrf2 target genes. In the cell model, we revealed that EGT could inhibit the increase in senescence-associated β-galactosidase-positive cells and p16 and γ-H2A.X positive cells induced by etoposide and activate PI3K/Akt/Nrf2 signaling. Moreover, a PI3K inhibitor blocked EGT protection against etoposide-induced cell death.Conclusion: The study showed EGT may play an important protective role against cell damage or death through the PI3K/Akt/Nrf2 signaling pathway in skin.Keywords: ergothioneine, skin aging, PI3K/Akt, Nrf2

Shanshan Liu,1,2 Xiaomeng Ge,3 Xizhan Xu,4 Kang Zhang,1 Xinxin Lu1 1Department of Laboratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Infection Management, The Affiliated Lianyungang Hospital of Xuzhou Medical University, The First People’s Hospital of Lianyungang, Jiangsu, People’s Republic of China; 3Microbial Resources and Big Data Center, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People’s Republic of China; 4Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Xinxin Lu, Department of Laboratory Medicine, Beijing Tongren Hospital, Capital Medical University, No. 1, Dongjiaomin Lane, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86-13911682566, Fax +8610-65125617, Email luxinxin2009@126.comPurpose: The clinical manifestations of pyogenic liver abscess (PLA) vary between patients with and without diabetes mellitus (DM). However, the relationship between PLA and the gut microbiome remains unknown. This study analyzed the composition of gut microbiota in PLA patients with and without DM and healthy controls (HCs) with the goal of identifying potential reasons for the observed variations in clinical manifestations.Patients and Methods: Using 16S ribosomal RNA(16S rRNA) gene sequencing, we analyzed the compositions of gut microbiota in 32 PLA patients with DM, 32 PLA patients without DM, and 29 matched HCs.Results: In PLA patients with DM, the D-dimer level, fibrinogen degradation products, and thrombin time were significantly higher compared to the PLA patients without DM (P < 0.05). The abundance and diversity of intestinal flora were reduced in both groups of PLA patients compared with the HCs (P < 0.05). Specifically, the PLA patients with DM showed significant decreases in the relative abundances of Bacteroides, Blautia, Prevotella9, and Faecalibacterium, whereas Enterococcus and Escherichia-Shigella were relatively more abundant (P < 0.05). Compared to PLA patients without DM, those with DM had lower relative abundances of Lactobacillus and Klebsiella (P < 0.05) and showed different bacterial flora, including Anaerosporobacter and Megamonas.Conclusion: PLA patients with DM exhibited more severe clinical manifestations of PLA compared to patients without DM. It is important to monitor blood coagulation in PLA patients with DM to prevent the development of thrombotic diseases. Additionally, PLA patients with DM exhibit distinct differences in the composition and diversity of their intestinal flora compared to both PLA patients without DM and HCs.Keywords: Gut microbiota, Pyogenic liver abscess, type 2 diabetes mellitus, 16S rRNA sequencing

Rui Zhou,1,2,&ast; Lijuan Fu,2,&ast; Shu Liu,2,&ast; Sanjie Gao,2 Zhifu Zhao,2 Wencai Jiang,2 Li Liu,2 Weiqiao Ren,2 Dongmei Xiang,2 Xing You,2 Chunyong Tang,2 Yukai Zhou,2 Yanqing Song,2 Juan Xie,2 Li Xie,2 Ru Yu,2 Xianjie Zhang,2 Dan Zhou,2 Jia Han,2 Leqiang Xia,2 Lize Xiong1 1Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Clinical Research Center for Anesthesiology and Perioperative Medicine, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 2Department of Anesthesiology, Deyang People’s Hospital, Deyang, 618000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leqiang Xia, Department of Anesthesiology, Deyang People’s Hospital, No. 173, Section 1, North Taishan Road, Deyang, Sichuan, 618000, People’s Republic of China, Tel +8613547098458, Email xialq123184@163.com Lize Xiong, Shanghai Fourth People’s Hospital, No. 1279, Sanmen Road, Shanghai, 200434, People’s Republic of China, Tel +86-21-55603002, Fax +86-21-56660851, Email mzkxlz@126.com; lizexiong@tongji.edu.cnPurpose: To compare the influences of propofol, ciprofol and remimazolam on dreaming during painless gastrointestinal endoscopy.Methods: This study was a single-center, prospective, parallel-design, double-blind, randomized clinical trial. Between May 2023 and October 2023, patients undergoing elective painless gastrointestinal endoscopy were recruited and randomly allocated into one of the three groups. Demographic data, intraoperative information, incidence of dreaming, insufficient anesthesia and intraoperative awareness, type of dream, patient satisfaction score, adverse events, and improvement of sleep quality were collected.Results: The difference in incidence of dreaming among the three groups was not significant (33.33% vs 48.33% vs 41.67%, p=0.061). The number of patients with intraoperative hypotension in the propofol group was larger than that of the remimazolam group (32 vs 12, p=0.001). However, the cases of intraoperative hypotension between propofol group and ciprofol group or ciprofol group and remimazolam group were comparable (32 vs 22, p=0.122; 22 vs 12, p=0.064). The percentage of insufficient anesthesia between propofol group and remimazolam group was significant (13.33% vs 1.67%, p=0.001), while no statistical difference was detected between propofol group and remimazolam group or ciprofol group and remimazolam group (13.33% vs 5.00%, p=0.025; 5.00% vs 1.67%, p=0.150). The ability of propofol to improve sleep quality at 1st post-examination day was significantly better than that of remimazolam (86.21% vs 72.88%, p=0.015), while it was not significant between propofol group and ciprofol group or ciprofol group and remimazolam group (86.21% vs 80.36%, p=0.236; 72.88% vs. 72.88%, p=0.181). Incidence of intraoperative awareness, intraoperative hypoxia, type of dream, satisfaction score, adverse events during recovery, and sleep improvement on the 7th post-examination day was not significant among the groups.Conclusion: Anesthesia with propofol, ciprofol and remimazolam, respectively, for gastrointestinal endoscopy did not induce statistical difference in the incidence of dreaming, despite that all of them are more likely to induce pleasant dreams.Keywords: propofol, ciprofol, remimazolam, endoscopic sedation, dreaming

Fei Li,1,&ast; Feifei Yan,2,&ast; Shengnan Liu,1,&ast; Rewaan Baheti,1 Yujia Feng,1 Jing Wan1 1Department of Cardiovascular Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430000, People’s Republic of China; 2Cardiac Ultrasound Department, Zhongnan Hospital of Wuhan University, Wuhan, 430000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Wan, Department of Cardiology, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, Hubei Province, 430071, People’s Republic of China, Tel +86-027-67813477, Email wanjing_zn@163.comPurpose: In essential hypertensive patients, cardiac remodeling may be associated with the risk of renal damage in the future which can be reflected by the estimated glomerular filtration rate (eGFR). Through retrospective analysis, we evaluated the potential of cardiac remodeling based on echocardiographic measurements to predict the risk of renal damage in the future with hypertensive patients.Methods: We retrospectively analyzed the relationship between the changes of left heart structure and function and renal damage for 510 patients with hypertension, who were diagnosed between 2016 to 2022. Demography data, clinical data, blood samples and echocardiographic variables were used for survival analysis, and the Cox proportional hazards regression model was used.Results: In our study, we found that age, serum creatinine (SCR), creatine kinase isoenzyme MB (CK MB), abnormal high-sensitivity troponin I (TNI), interventricular septum thickness (IVST) and left ventricular ejection fraction (LVEF) could be used as independent predictors in risk of renal impairment in hypertensive patients (p< 0.05). Combined in a score where one point was given for the presence of each of the parameters above, this score could strongly predict renal function damage in the future (p< 0.05). In receiver operating characteristics (ROC) curve analyses, the area under the curve of the risk factor score was 0.849 (P< 0.001).Conclusion: In essential hypertensive patients, LVEF and IVST can predict the risk of future adverse renal outcomes. Moreover, combining risk variables into a simplified score may enable to assess the risk of renal impairment in hypertensive patients at an early stage.Keywords: hypertension, echocardiography, changes of cardiac structure and function, progression of renal damage, hypertensive nephropathy

Di Zhang,1,&ast; Yu Guan,1,&ast; Xiuxiu Zhou,1 Mingzi Zhang,2 Yu Pu,1 Pengchen Gu,2 Yi Xia,1 Yang Lu,2 Jia Chen,2 Wenting Tu,1 Kunyao Huang,2 Jixin Hou,2 Hua Yang,2 Chicheng Fu,2 Qu Fang,2 Chuan He,2 Shiyuan Liu,1 Li Fan1 1Department of Radiology, Second Affiliated Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Scientific Research Department, Shanghai Aitrox Technology Corporation Limited, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Fan; Shiyuan Liu, Department of Radiology, Second Affiliated Hospital, Naval Medical University, 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Tel +13564684699 ; +13761304518, Fax +86 21 63587668, Email czyxfl@smmu.edu.cn; radiology_cz@163.comPurpose: To develop a novel method for calculating small airway resistance using computational fluid dynamics (CFD) based on CT data and evaluate its value to identify COPD.Patients and Methods: 24 subjects who underwent chest CT scans and pulmonary function tests between August 2020 and December 2020 were enrolled retrospectively. Subjects were divided into three groups: normal (10), high-risk (6), and COPD (8). The airway from the trachea down to the sixth generation of bronchioles was reconstructed by a 3D slicer. The small airway resistance (RSA) and RSA as a percentage of total airway resistance (RSA%) were calculated by CFD combined with airway resistance and FEV1 measured by pulmonary function test. A correlation analysis was conducted between RSA and pulmonary function parameters, including FEV1/FVC, FEV1% predicted, MEF50% predicted, MEF75% predicted and MMEF75/25% predicted.Results: The RSA and RSA% were significantly different among the three groups (p< 0.05) and related to FEV1/FVC (r = − 0.70, p < 0.001; r = − 0.67, p < 0.001), FEV1% predicted (r = − 0.60, p = 0.002; r = − 0.57, p = 0.004), MEF50% predicted (r = − 0.64, p = 0.001; r = − 0.64, p = 0.001), MEF75% predicted (r = − 0.71, p < 0.001; r = − 0.60, p = 0.002) and MMEF 75/25% predicted (r = − 0.64, p = 0.001; r = − 0.64, p = 0.001).Conclusion: Airway CFD is a valuable method for estimating the small airway resistance, where the derived RSA will aid in the early diagnosis of COPD.Keywords: COPD, small airway disease, CT, fluid dynamics

Si Liu, Dan Yang, Wen Li, Qiuping Chen, Danni Lu, Liang Xiong, Junjie Wu, Hui Ao, Lihua Huang State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of ChinaCorrespondence: Lihua Huang; Hui Ao, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China, Email huanglihua@cdutcm.edu.cn; aohui2005@126.comPurpose: Polygala tenuifolia Willd. (PT), a traditional Chinese medicinal plant extensively employed in managing Alzheimer’s disease, exhibits notable gastrointestinal side effects as highlighted by prior investigations. In contrast, Magnolia officinalis Rehd. et Wils (MO), a traditional remedy for gastrointestinal ailments, shows promising potential for ameliorating this adverse effect of PT. The objective of this study is to examine the underlying mechanism of MO in alleviating the side effects of PT.Methods: Hematoxylin-eosin (H&E) staining was used to observe the structural damage of zebrafish intestine, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors and oxidative stress. The integrity of the intestinal tight junctions was examined using transmission electron microscope (TEM). Moreover, the expression of intestinal barrier genes and PI3K/AKT/NF-κB signaling pathway-related genes was determined through quantitative real-time PCR. The changes in intestinal microbial composition were analyzed using 16S rRNA and metagenomic techniques.Results: MO effectively ameliorated intestinal pathological damage and barrier gene expression, and significantly alleviated intestinal injury by reducing the expression of inflammatory cytokines IL-1β, IL-6, TNF-α, and inhibiting the activation of PI3K/AKT/NF-κB pathway. Furthermore, MO could significantly increase the relative abundance of beneficial microorganisms (Lactobacillus, Blautia and Saccharomyces cerevisiae), and reduce the relative abundance of pathogenic bacteria (Plesiomonas and Aeromonas).Conclusion: MO alleviated PT-induced intestinal injury, and its mechanism may be related to the inhibition of PI3K/AKT/NF-κB pathway activation and regulation of intestinal flora.Keywords: polygala tenuifolia, PI3K/AKT/NF-κB, gut microbiota, inflammation, intestinal injury

Xin Yang,1 Xiaoguang Cui,1 Xiao Yang,2 Bincheng Ren,1 Xiaojing Cheng,1 Xinrui Zhao,1 Shanshan Liu,1 Tian Tian,1 Hui Zhao,1 Li Qu,1 Xueyi Li1 1Department of Rheumatology, Xi’an Jiaotong University Second Affiliated Hospital, Xi’an, People’s Republic of China; 2Scientific Research Center and Precision Medical Institute, Xi’an Jiaotong University Second Affiliated Hospital, Xi’an, People’s Republic of ChinaCorrespondence: Xueyi Li, Department of Rheumatology, Xi’an Jiaotong University Second Affiliated Hospital, Xi’an, People’s Republic of China, Tel +86 13992891987, Fax +86 02987679832, Email li-xueyi@139.comPurpose: This study aimed to assess liver involvement and investigate its correlation with rapidly progressive interstitial lung disease (RP-ILD) and mortality in anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5 positive) DM patients.Patients and Methods: This retrospective study included 159 patients diagnosed with anti-MDA5 positive DM or anti-synthetase syndrome (ASyS). Clinical features and laboratory findings were compared between patients with anti-MDA5 positive DM and patients with ASyS. In the anti-MDA5 positive DM cohort, clinical features and laboratory findings between patients with liver involvement and without liver involvement were further compared. The effects of liver involvement on the overall survival (OS) and development of RP-ILD were also analyzed using Kaplan–Meier method and Cox regression analysis.Results: Levels of serum aspartate aminotransferase (AST), alanine transaminase (ALT), γ-glutamyl transferase (γGT) and alkaline phosphatase (ALP) were all significantly higher in patients with anti-MDA5 positive DM than those in patients with ASyS. In our cohort of anti-MDA5 positive DM patents, 31 patients (34.4%) were complicated with liver involvement. Survival analysis revealed that serum ferritin > 1030.0 ng/mL (p< 0.001), ALT > 103.0 U/l (p< 0.001), AST > 49.0 U/l (p< 0.001), γGT > 82.0 U/l (p< 0.001), ALP > 133.0 U/l (p< 0.001), lactate dehydrogenase (LDH)> 474.0 U/l (p< 0.001), plasma albumin (ALB) < 35.7 g/l (p< 0.001) and direct bilirubin (DBIL) > 2.80 μmol/l (p=0.002) predicted poor prognosis. The incidence of RP-ILD increased remarkably in patients with liver involvement compared to patients without liver involvement (58.1% vs 22.0%, p=0.001). Multivariate analysis revealed that elevated serum ALT level was an independent risk factor for mortality (HR 6.0, 95% CI 2.3, 16.2, p< 0.001) and RP-ILD (HR 5.9, 95% CI 2.2, 15.9, p< 0.001) in anti-MDA5 positive DM patents.Conclusion: Liver involvement is common in patients with anti-MDA5 positive DM. Elevated serum ALT level was an independent risk factor for RP-ILD and mortality in patients with anti-MDA5 positive DM.Keywords: anti-melanoma differentiation-associated gene 5 antibody, liver involvement, ferritin, macrophage, interstitial lung disease, dermatomyositis

Yanting Ma,1 Yongyuan Li,2 Zhanfeng Zhang,3 Guomei Du,4 Ting Huang,1 Zhi Zhong Zhao,5 Shou Liu,1 Zhancui Dang1 1Department of Public Health, Medical College, Qinghai University, Xining, Qinghai, People’s Republic of China; 2Disease Control department, Huangzhong District health Bureau, Xining, Qinghai, People’s Republic of China; 3Huangzhong District, Duoba County Health Services Center, Xining, Qinghai, People’s Republic of China; 4Clinical Laboratory, Qinghai Red Cross Hospital, Xining, Qinghai, People’s Republic of China; 5Disease Control Department, Qinghai Provincial Center for Endemic Disease Control and Prevention, Xining, Qinghai, People’s Republic of ChinaCorrespondence: Shou Liu; Zhancui Dang, Email liushou2004@aliyun.com; yxyyy2019@163.comPurpose: The prevalence of metabolic syndrome (MetS) is increasing worldwide, and early prediction of MetS risk is highly beneficial for health outcomes. This study aimed to develop and validate a nomogram to predict MetS risk in Qinghai Province, China, and it provides a methodological reference for MetS prevention and control in Qinghai Province, China.Patients and Methods: A total of 3073 participants living between 1900 and 3710 meters above sea level in Qinghai Province participated in this study between March 2014 and March 2016. We omitted 12 subjects who were missing diagnostic component data for MetS, ultimately resulting in 3061 research subjects, 70% of the subjects were assigned randomly to the training set, and the remaining subjects were assigned to the validation set. The least absolute shrinkage and selection operator (LASSO) regression analysis method was used for variable selection via running cyclic coordinate descent with 10-fold cross-validation. Multivariable logistic regression was then performed to develop a predictive model and nomogram. The receiver operating characteristic (ROC) curves was used for model evaluation, and calibration plot and decision curve analysis (DCA) were used for model validation.Results: Of 24 variables studied, 6 risk predictors were identified by LASSO regression analysis: hyperlipidaemia, hyperglycemia, abdominal obesity, systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index (BMI). A prediction model including these 6 risk factors was constructed and displayed good predictability with an area under the ROC curve of 0.914 for the training set and 0.930 for the validation set. DCA revealed that if the threshold probability of MetS is less than 82%, the application of this nomogram is more beneficial than both the treat-all or treat-none strategies.Conclusion: The nomogram developed in our study demonstrated strong discriminative power and clinical applicability, making it a valuable reference for meets prevention and control in the plateau areas of Qinghai Province.Keywords: metabolic syndrome, nomogram, prediction model, plateau section

Yan Jin,1 Yiju Wang,2 Shusen Liu,3 Sifang Niu,4 Hao Sun,1 Yan Liu,5 Ning Liu6 1School of Clinical Medicine, Jining Medical University, Jining, Shandong, 272002, People’s Republic of China; 2School of Mental Health, Jining Medical University, Jining, Shandong, 272002, People’s Republic of China; 3School of Pharmacy, Harbin University of Commerce, Harbin, Heilongjiang, 150076, People’s Republic of China; 4School of Public Health, Binzhou Medical University, Binzhou, Shandong, 264003, People’s Republic of China; 5School of Public Health, Jining Medical University, Jining, Shandong, 272002, People’s Republic of China; 6School of Basic Medicine, Jining Medical University, Jining, Shandong, 272067, People’s Republic of ChinaCorrespondence: Yan Liu; Ning Liu, Email hakunaly@163.com; 631864@qq.comAim: Stressful life events have a significant impact on the mental health of college students. Depression, as a prevalent psychological issue, has garnered attention in the field of college student mental health and is closely linked to it. Additionally, parenting style is identified as an important factor influencing the development of college students’ mental health. Therefore, this study aims to explore the relationship between these three factors.Methods: A total of 8079 first-year college students from two medical universities in Shandong Province, China were surveyed. The Beck Depression Inventory was utilized to evaluate depressive symptoms among the college students, while the Adolescent Self-rating Life Events Checklist and the Egna Minnen Beträfande Uppfostran were employed to gather data. Subsequently, the SPSS macro program PROCESS was utilized to analyze both the mediating and moderating effects. All statistical analyses were conducted using SPSS 26.0.Results: The study found a detection rate of 6.3% for depressive symptoms among college students. The correlation analysis of this study showed that the stressful life events of college students were significantly positively correlated with depressive symptoms (r=0.261, p< 0.01). Each dimension of parenting style was associated with depressive symptoms in different degrees and directions. At the same time, parenting styles of all sizes play a partial mediating role between stressful life events and depressive symptoms in college students, gender plays a crucial regulatory role in this mediation.Conclusion: Stressful life events experienced by college students have a significant impact on their mental health. Early intervention through positive parenting styles from parents may prove to be beneficial in promoting the development of good mental health among college students.Keywords: college students, stressful life events, depressive symptoms, parenting style, gender

Mengjin Hao,1,2 You Lv,1 Siyuan Liu,1 Weiying Guo1 1Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China; 2Department of Endocrinology, Jining No. 1 People’s Hospital, Jining, Shandong, 272000, People’s Republic of ChinaCorrespondence: Weiying Guo, Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China, Email guowy@jlu.edu.cnAbstract: In recent years, obesity has become one of the major diseases that affect human health and consume human health resources, especially when it causes comorbidities such as hypertension, diabetes, cardiovascular disease and kidney disease. Many studies have demonstrated that obesity is associated with the development of chronic kidney disease and can exacerbate the progression of end-stage renal disease. This review described the mechanisms associated with the development of obesity-associated nephropathy and the current relevant therapeutic modalities, with the aim of finding new therapeutic targets for obesity-associated nephropathy. The mechanisms of obesity-induced renal injury include, in addition to the traditional alterations in renal hemodynamics, the involvement of various mechanisms such as macrophage infiltration in adipose tissue, alterations in adipokines (leptin and adiponectin), and ectopic deposition of lipids. At present, there is no “point-to-point” treatment for obesity-induced kidney injury. The renin-angiotensin-aldosterone system (RAAS) inhibitors, sodium-dependent glucose transporter 2 (SGLT-2) inhibitors and bariatric surgery described in this review can reduce urinary protein to varying degrees and delay the progression of kidney disease. In addition, recent studies on the therapeutic effects of intestinal flora on obesity may reduce the incidence of obesity-related kidney disease from the perspective of primary prevention. Both of these interventions have their own advantages and disadvantages, so the continuous search for the mechanism of obesity-induced related kidney disease will be extremely helpful for the future treatment of obesity-related kidney disease.Keywords: obesity, kidney injury, inflammation, oxidative stress, adiponectin, leptin

Ling Shi,1 Yunjun Zhou,2 Yongkui Yin,1 Jin Zhang,3 Kaiyuan Chen,1 Sen Liu,1 Peijian Chen,1 Hua Jiang,2 Jieting Liu,1 Yan Wu1 1College of Life Science, Mudanjiang Medical University, Mudanjiang, 157000, People’s Republic of China; 2The Affiliated Hongqi Hospital, Mudanjiang Medical University, Mudanjiang, 157000, People’s Republic of China; 3Clinical Laboratory, Zhejiang Medical & Health Group Quzhou Hospital, Quzhou, 324004, People’s Republic of ChinaCorrespondence: Yan Wu; Jieting Liu, College of Life Science, Mudanjiang Medical University, 3 Tong Xiang Street, Ai Min District, Mudanjiang, 157000, People’s Republic of China, Tel +86-0453-6984647, Email wuyan@mdjmu.edu.cn; ttiebj1@163.comAbstract: Geriatric diseases are a group of diseases with unique characteristics related to senility. With the rising trend of global aging, senile diseases now mainly include endocrine, cardiovascular, neurodegenerative, skeletal, and muscular diseases and cancer. Compared with younger populations, the structure and function of various cells, tissues and organs in the body of the elderly undergo a decline as they age, rendering them more susceptible to external factors and diseases, leading to serious tissue damage. Tissue damage presents a significant obstacle to the overall health and well-being of older adults, exerting a profound impact on their quality of life. Moreover, this phenomenon places an immense burden on families, society, and the healthcare system.In recent years, stem cell-derived exosomes have become a hot topic in tissue repair research. The combination of these exosomes with biomaterials allows for the preservation of their biological activity, leading to a significant improvement in their therapeutic efficacy. Among the numerous biomaterial options available, hydrogels stand out as promising candidates for loading exosomes, owing to their exceptional properties. Due to the lack of a comprehensive review on the subject matter, this review comprehensively summarizes the application and progress of combining stem cell-derived exosomes and hydrogels in promoting tissue damage repair in geriatric diseases. In addition, the challenges encountered in the field and potential prospects are presented for future advancements.Keywords: exosomes, biomaterials, hydrogels, geriatric diseases, injury repair

Lanlang Zhang,1 Lixia Huang,2 Shanshan Liu,3 Xiaofeng Sun4 1Department of Haemodialysis, Fuyong People’s Hospital of Baoan District, Shenzhen, Guangdong Province, 518103, People’s Republic of China; 2Department of Gastrology, Fuyong People’s Hospital of Baoan District, Shenzhen, Guangdong Province, 518103, People’s Republic of China; 3Nursing Department, Fuyong People’s Hospital of Baoan District, Shenzhen, Guangdong Province, 518103, People’s Republic of China; 4Department of Ultrasound, Shenzhen Baoan Women’s and Children’s Hospital, Shenzhen, Guangdong Province, 518000, People’s Republic of ChinaCorrespondence: Xiaofeng Sun, Department of Ultrasound, Shenzhen Baoan Women’s and Children’s Hospital, Shenzhen, Guangdong Province, 518000, People’s Republic of China, Tel +86-13723457417, Email 350787457@qq.comAbstract: This study aimed to optimize bowel preparation efficacy for colonoscopy in elderly constipation patients. A 71-year-old patient with chronic constipation and a history of poor bowel preparation. To address these challenges, we implemented a personalized strategy combining of PEG administration and walking exercise. The PEG was administered according to a protocol, with intermittent exercise breaks of 10 minute. Bowel cleanliness was assessed using the Boston Bowel Preparation Scale (BBPS). Adverse reactions and tolerance were closely monitored throughout the intervention. The patient’s BBPS score improved from 3 to 8 post-intervention. The exercise intervention was well-tolerated (rating I), and mild nausea was observed only after the first PEG dose. No severe adverse reactions occurred. Subsequent Follow-up revealed symptom relief. The personalized approach combining (PEG and exercise intervention) successfully improved bowel preparation quality in the elderly constipation patient undergoing colonoscopy. This approach considers age-related changes in gastrointestinal function and activity level, offering an effective strategy to improve patient tolerance and reduce adverse reactions during bowel preparation. The findings underscore the importance of tailoring interventions for elderly constipation patients to optimize the colonoscopy experience.Keywords: compound polyethylene glycol electrolyte powder, exercise intervention plan, bowel preparation, colonoscopy, elderly, constipation

Suqing Liu,1 Fengling Li,1 Qinghua Cao,2 Ning Li,1 Qian Gao1 1Department of Gynaecology and Obstetrics, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, People’s Republic of China; 2Department of Pathology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, People’s Republic of ChinaCorrespondence: Fengling Li, Department of Gynecology and Obstetrics, Yantai Affiliated Hospital of Binzhou Medical University, Muping District, Yantai, Shandong, People’s Republic of China, Email sdbzlsq1989@163.comAbstract: Gastric adenocarcinoma (GAS) is a rare subtype of mucinous adenocarcinoma characterized by gastric differentiation and is unrelated to human papillomavirus (HPV) infection. This report discusses a 40-year-old female who presented with abdominal distension accompanied by increased abdominal circumference. CT of the abdomen and pelvis showed a large 21.0&ast;12.7&ast;26.0 cm mass later diagnosed as GAS combined with squamous cell carcinoma on surgical pathology. Immunohistological staining of GAS was positive for CK7, MUC6, PAX-8 CEA, and P53 (wild type) and negative for CDX2, CK20, ER, PR, P16, and WT1. The proliferative index (Ki-67) was 20%. Immunohistochemical staining of squamous cell carcinoma was positive for P16 and P53 (wild type), and the proliferative index (Ki-67) was 90%. However, the pathogenesis and molecular mechanisms of GAS have not been fully elucidated. As more cases are identified and reported, additional targeted therapies can be developed and tested in these patients.Keywords: cervical cancer, gastric type, adenocarcinoma

Shuzhou Liu,1,&ast; Hao Zhao,2,&ast; Xiaoyi Li2 1Department of Head & Neck Surgery, Hainan General Hospital, Haikou, 570311, People’s Republic of China; 2Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyi Li, Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuai Fu Yuan, Dongcheng District, Beijing, 100730, People’s Republic of China, Email li.xiaoyi@263.netIntroduction: Medullary thyroid carcinoma (MTC), a rare malignancy, requires early diagnosis for optimal patient outcomes. An important aspect of MTC diagnosis is the assessment of serum biomarkers. This review aimed to evaluate the use of serum biomarkers in the diagnosis, prognosis, and follow-up of MTC.Methods: A thorough search of PubMed covering 1975 to 2022 was conducted to identify English-language articles on MTC serum biomarkers.Results: The review revealed that calcitonin (Ctn) and carcinoembryonic antigen (CEA) remain the most important serum biomarkers for MTC diagnosis and management. Despite limited studies on procalcitonin (PCT), its stability and ability to exclude interference from inflammation make it a valuable potential marker of MTC. Although the positive rate of serum CA19-9 levels in MTC patients was not high, it can be used as an indicator of poor prognosis in advanced MTC. Other serum markers, including chromogranin A, gastrin-releasing peptide precursor, and neurospecific enolase, did not show any unique value in MTC diagnosis and management.Conclusion: Taken together, this review emphasized the importance of serum biomarkers, particularly Ctn and CEA, in the diagnosis and management of MTC. PCT shows promise as a valuable potential marker, whereas CA19-9 can be used as a prognostic indicator of advanced MTC. Further research is needed to validate the significance of these serum biomarkers in MTC and determine the effects of confounding factors on their levels. Clinicians should consider using these markers in MTC diagnosis, prognosis, and follow-up, particularly for patients with advanced disease.Keywords: medullary thyroid carcinoma, serum biochemical markers, calcitonin, carcinoembryonic antigen, procalcitonin

Longjiang Zhou,1,&ast; Haitao Xiang,2,&ast; Susu Liu,3 Honglin Chen,4 Yuanwei Yang,4 Jianyong Zhang,4 Wei Cai4 1Department of Neurology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225012, People’s Republic of China; 2Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, 215028, People’s Republic of China; 3School of Life Science and Technology, Xidian University and Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, Xi’an, 710126, People’s Republic of China; 4Department of Neurosurgery, Suqian First Hospital, Suqian, 223800, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Cai; Jianyong Zhang, Department of Neurosurgery, Suqian First Hospital, No. 120, Suzhi Road, Sucheng District, Suqian, Jiangsu Province, People’s Republic of China, Tel +86 15162908957 ; +86 15261296169, Fax +86 527 80766363 ; +86 527 80766155, Email doccaiwei@126.com; 935349804@qq.comPurpose: Hypoxia is often associated with glioma chemoresistance, and alleviating hypoxia is also crucial for improving treatment efficacy. However, although there are already some methods that can improve efficacy by alleviating hypoxia, real-time monitoring that can truly achieve hypoxia relief and efficacy feedback still needs to be explored.Methods: AQ4N/Gd@PDA-FA nanoparticles (AGPF NPs) were synthesized using a one-pot method and were characterized. The effects of AGPF NPs on cell viability, cellular uptake, and apoptosis were investigated using the U87 cell line. Moreover, the effectiveness of AGPF NPs in alleviating hypoxia was explored in tumor-bearing mice through photoacoustic imaging. In addition, the diagnosis and treatment effect of AGPF NPs were evaluated by magnetic resonance imaging (MRI) and bioluminescent imaging (BLI) on orthotopic glioma mice respectively.Results: In vitro experiments showed that AGPF NPs had good dispersion, stability, and controlled release. AGPF NPs were internalized by cells through endocytosis, and could significantly reduce the survival rate of U87 cells and increase apoptosis under irradiation. In addition, we monitored blood oxygen saturation at the tumor site in real-time through photoacoustic imaging (PAI), and the results showed that synergistic mild-photothermal therapy/chemotherapy effectively alleviated tumor hypoxia. Finally, in vivo anti-tumor experiments have shown that synergistic therapy can effectively alleviate hypoxia and inhibit the growth of orthotopic gliomas.Conclusion: This work not only provides an effective means for real-time monitoring of the dynamic feedback between tumor hypoxia relief and therapeutic efficacy, but also offers a potential approach for the clinical treatment of gliomas.Keywords: gliomas, hypoxia relief, photothermal therapy, real-time monitoring, photoacoustic imaging

Xiaofang Xu,1 Yang Li,2 Shuyuan Liu,2 Wenchao Wang2 1School of Education Science, Luoyang Normal University, Luoyang, 471934, People’s Republic of China; 2Beijing Key Laboratory of Applied Experimental Psychology, National Demonstration Center for Experimental Psychology Education (Beijing Normal University), Faculty of Psychology, Beijing Normal University, Beijing, 100875, People’s Republic of ChinaCorrespondence: Wenchao Wang, Faculty of Psychology, Beijing Normal University, No. 19 Xinjiekouwai Street, Beijing, 100875, People’s Republic of China, Tel/Fax +8601058801184, Email psychao@bnu.edu.cnPurpose: Bullying victimization is a serious issue among college students, which might affect the development of their social behaviors. Based on the theory of stress and coping and emotion regulation theory, the present study examined the mediating role of self-compassion and trauma-related shame between bullying victimization and cyber aggression/prosocial behavior.Patients and Methods: We gathered self-reporting data on bullying victimization, self-compassion, trauma-related shame, cyber aggression, and prosocial behavior from 634 college students in China using a three-wave longitudinal design survey. Structural equation modeling was used to test temporal mediation.Results: The results showed that bullying victimization predicted cyber aggression and prosocial behavior via trauma-related shame and the chain effect of self-compassion and trauma-related shame. Moreover, self-compassion also mediated the relationship between bullying victimization and prosocial behavior.Conclusion: The study revealed the different emotional processes that underlie both bullying victimization and different social behaviors. It also contributes to more effective prevention and intervention measures for the social adaptation of bullied students.Keywords: bullying victimization, self-compassion, trauma-related shame, cyber aggression, prosocial behavior, emotional mechanisms

Yunxiang Hu,1,2,&ast; Rui Yang,1,2,&ast; Sanmao Liu,1,2,&ast; Zefeng Song,3 Hong Wang1,2 1Department of Orthopedics, Central Hospital of Dalian University of Technology, Dalian City, Liaoning Province, People’s Republic of China; 2School of Graduates, Dalian Medical University, Dalian City, Liaoning Province, People’s Republic of China; 3School of Graduates, Dalian University of Technology, Dalian City, Liaoning Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong WangDepartment of Orthopedics, Central Hospital of Dalian University of Technology, No. 826, Southwestern Road, Shahekou District, Dalian City, Liaoning Province, People’s Republic of China, Email wanghong@dmu.edu.cnAbstract: Low back pain (LBP) is a common condition that has substantial consequences on individuals and society, both socially and economically. The primary contributor to LBP is often identified as intervertebral disc degeneration (IVDD), which worsens and leads to significant spinal problems. The conventional treatment approach for IVDD involves physiotherapy, drug therapy for pain management, and, in severe cases, surgery. However, none of these treatments address the underlying cause of the condition, meaning that they cannot fundamentally reverse IVDD or restore the mechanical function of the spine. Nanotechnology and regenerative medicine have made significant advancements in the field of healthcare, particularly in the area of nanodrug delivery systems (NDDSs). These approaches have demonstrated significant potential in enhancing the efficacy of IVDD treatments by providing benefits such as high biocompatibility, biodegradability, precise drug delivery to targeted areas, prolonged drug release, and improved therapeutic results. The advancements in different NDDSs designed for delivering various genes, cells, proteins and therapeutic drugs have opened up new opportunities for effectively addressing IVDD. This comprehensive review provides a consolidated overview of the recent advancements in the use of NDDSs for the treatment of IVDD. It emphasizes the potential of these systems in overcoming the challenges associated with this condition. Meanwhile, the insights and ideas presented in this review aim to contribute to the advancement of precise IVDD treatment using NDDSs.Keywords: lumbar disc herniation, intervertebral disc degeneration, nanocarrier drug delivery system, targeted therapy, regenerative medicine

Shixuan Liu,&ast; Lin Liu,&ast; Xinyue Lu, Tingfeng Yao Department of Rehabilitation, School of Sport Health, Nanjing Sport Institute, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Liu, Department of Rehabilitation, School of Sport Health, Nanjing Sport Institute, Nanjing, People’s Republic of China, Email liulinst1989@126.comPurpose: Myofascial trigger points (MTrPs) are the main cause of myofascial pain syndrome (MPS), and patients with MPS also have symptoms of sympathetic abnormalities. Consequently, this study aimed to investigate the potential relationship between MTrPs and sympathetic nerves.Materials and Methods: Twenty-four seven-week-old male rats were randomly divided into four groups (six rats every group). Groups I and II were kept in normal condition (n=12), and groups III and IV underwent MTrPs modelling (n=12). After successful MTrPs modelling, differences in sympathetic outcomes between the MTrPs groups (III and IV) and non-MTrPs groups (I and II) were observed. Sympathetic blockade was then applied to groups III and I (n=12). Data were collected on peak inversion spontaneous potentials (PISPs) and the H-reflex-evoked electromyography during spontaneous discharge at the MTrPs before and after sympathetic blockade.Results: Systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate were significantly higher in the MTrPs group than in the non-MTrPs group (P< 0.05). Compared with group I, group III had the PISPs potential lower wave amplitude, shorter duration and amplitude-to-duration ratio, and lower H latency and latency difference H-M (P< 0.05). Compared with group IV, group III had the PISPs potential lower wave amplitude, duration, amplitude-to-duration ratio, M-wave latency, H maximum wave amplitude, and maximal wave amplitude ratio H/M (P< 0.05). The changes before and after sympathetic blockade in the MTrPs group were significant, and the amplitude, duration, and amplitude-to-duration ratio of the PISPs potentials were lower after the blockade (P< 0.05).Conclusion: MTrPs and sympathetic nerves interact with each other forming a specific relationship. MTrPs sensitize sympathetic nerves, and sympathetic nerve abnormalities affect local muscle myoelectric hyperactivity, leading to MTrPs. This finding is instructive for the clinical management of sympathetic disorders.Keywords: myofascial trigger point, sympathetic blockade, electromyography, H-reflex, myofascial pain syndrome

Ying Zhang,&ast; Sainan Liu,&ast; Qi Miao, Xu Zhang, He Wei, Shuang Feng, Xiaofei Li The First Affiliated Hospital of China Medical University, Shenyang, 110001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaofei Li, Transplantation and Hepatobiliary Department, The First Affiliated Hospital of China Medical University, Shenyang, 110001, People’s Republic of China, Tel +15940564748, Email lixiaofei0603@aliyun.comPurpose: Kidney transplant recipients (KTRs) may experience symptoms that increase their fear of progression (FoP), but a dearth of research examines the issue from a patient-centered perspective. Our study aimed to first determine the category of symptom burden, then to explore the differences in characteristics of patients in different subgroups, and finally to analyze the impact of symptom subgroup on FoP.Patients and Methods: Sociodemographic and Clinical Characteristics, Symptom Experience Scale, and Fear of Progression Questionnaire-Short Form were used. Latent class analysis was used to group KTRs according to the occurrence of symptoms. We used multivariate logistic regression to analyze the predictors of different subgroups. The differences in FoP among symptom burden subgroups were analyzed by hierarchical multiple regression.Results: Three subgroups were identified, designated all-high (20.5%), moderate (39.9%), and all-low (39.6%) according to their symptom occurrence. Multivariate logistic regression showed that gender, post-transplant time, per capita monthly income, and hyperuricemia were the factors that distinguished and predicted the all-high subgroup (P < 0.05). Hierarchical multiple regression showed that symptom burden had a significant effect on FoP (class1 vs class3: β = 0.327, P < 0.001; class2 vs class3: β = 0.104, P = 0.046), explaining the 8.0% variance of FoP (ΔR2 = 0.080).Conclusion: KTRs generally experience moderate or low symptom burden, and symptom burden is an influencing factor in FoP. Identifying the traits of KTRs with high symptom burden can help clinicians develop targeted management strategies and ease FoP of KTRs.Keywords: kidney transplant, symptom burden, fear of progression, latent class analysis

Zhisheng Huang,1,2 Zuowang Cheng,3 Xia Deng,4 Ying Yang,5 Na Sun,5 Peibin Hou,5 Ruyue Fan,5 Shuai Liu6,7 1Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, National Regional Center for Respiratory Medicine, Jiangxi Hospital of China-Japan Friendship Hospital, Nanchang, Jiangxi, People’s Republic of China; 3Department of Clinical Laboratory, Zhangqiu District People’s Hospital Affiliated to Jining Medical University, Jinan, Shandong, People’s Republic of China; 4School of Public Health, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China; 5Shandong Center for Disease Control and Prevention, Jinan, Shandong, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 7Shandong Key Laboratory of Infectious Respiratory Disease, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Shuai Liu; Ruyue Fan, Email liushuai_sam@163.com; fanruyue2022@163.comBackground: Coronavirus disease 2019 (COVID-19) is a respiratory infectious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The objective of this study is to identify reliable and accurate biomarkers for the early stratification of disease severity, a crucial aspect that is currently lacking for the impending phases of the next COVID-19 pandemic.Methods: In this study, we identified important module and hub genes related to clinical severe COVID-19 using differentially expressed genes (DEGs) screening combing weighted gene co-expression network analysis (WGCNA) in dataset GSE213313. We further screened and confirmed these hub genes in another two new independent datasets (GSE172114 and GSE157103). In order to evaluate these key genes’ stability and robustness for diagnosing or predicting the progression of illness, we used RT-PCR validation of selected genes in blood samples obtained from hospitalized COVID-19 patients.Results: A total of 968 and 52 DEGs were identified between COVID-19 patients and normal people, critical and non-critical patients, respectively. Then, using WGCNA, 10 modules were constructed. Among them, the blue module positively associated with clinic disease severity of COVID-19. From overlapped section between DEGs and blue module, 12 intersected common differential genes were obtained. Subsequently, these hub genes were validated in another two new independent datasets as well and 9 genes that overlapped showed a highly correlation with disease severity. Finally, the mRNA expression levels of these hub genes were tested in blood samples from COVID-19 patients. In severe cases, there was increased expression of MCEMP1, ANXA3, CD177, and SCN9A. In particular, MCEMP1 increased with disease severity, which suggested an unfavorable development and a frustrating prognosis.Conclusion: Using comprehensive bioinformatical analysis and the validation of clinical samples, we identified four major candidate genes, MCEMP1, ANXA3, CD177, and SCN9A, which are essential for diagnosis or development of COVID-19.Keywords: COVID-19, differentially expressed genes, WGCNA, hub genes, neutrophil

Miaomiao Li,1,2 Xiaoyu Wang,1,2 Fang Wang,3 Fengqi Wang,1,2 Dehua Zhao,4 Shiguo Liu1,2 1Department of Medical Genetic, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Prenatal Diagnosis Center, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 3Endocrinology Department, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 4Neonatal Screening Center, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Dehua Zhao, The Third Affiliated Hospital of Zhengzhou University, Neonatal Screening Center, Zhengzhou, Henan, 450052, People’s Republic of China, Email zhaodehua369@163.com Shiguo Liu, The Affiliated Hospital of Qingdao University, Department of Medical Genetic, Prenatal Diagnosis Center, Qingdao, Shandong, 266003, People’s Republic of China, Email liushiguo@qdu.edu.cnBackground and Objective: Congenital hypothyroidism (CH) is indeed a prevalent neonatal endocrine disorder, affecting approximately 1 in 2000– 3000 newborns worldwide, and 1 in 2400 newborns in China. Despite its high incidence, the genetic causes of CH, particularly those related to thyroid dysgenesis (TD), are still not well understood. However, previous studies have suggested that JAG1 may be a potential susceptibility gene for congenital thyroid defects. To explore the association between JAG1 and CH, we screened JAG1 variants in a large cohort of 813 CH patients.Methods: We performed genetic analysis of JAG1 using next-generation sequencing in 813 CH cases. The pathogenicity of the variants was assessed by bioinformatics softwares, protein sequence conservation analysis, and hydrophobic analysis. Further genetic analysis was conducted targeting 20 CH-related genes in these 25 JAG1 variant carriers.Results: We identified 10 pathogenic missense mutations (p.V45L, p.V272I, p.P552L, p.G610E, p.G852D, p.A891T, p.E1030K, p.R1060W, p.A1131T, p.P1174L) carried by 25 patients, the mutation rate of JAG1 in CH was 3.08%. Among these 25 patients, 16 with 1 variant, 6 with 2 variants, and the other 3 with 3 variants. Our findings indicated that JAG1 variants confer genetic susceptibility to both TD and DH, but with different inheritance models. JAG1 variants lead to TD mainly through monogenic model, while for DH cases, both monogenic mechanisms and oligogenic mechanisms play a pivotal role. Oligogenicity may contribute to the disease severity of DH.Conclusion: JAG1 is a shared genetic factor in TD and DH, with a detection rate of 3.08% in Chinese individuals with CH. A comparison between the oligogenic and monogenic groups suggests a gene dosage effect in CH. Patients with the same JAG1 mutation exhibit diverse clinical phenotypes, indicating complex mechanisms underlying phenotypic heterogeneity.Keywords: congenital hypothyroidism, JAG1, pathogenic variant, inheritance model, phenotypic heterogeneity

Baojiang Liu,&ast; Song Gao,&ast; Jianhai Guo, Fuxin Kou, Shaoxing Liu, Xin Zhang, Aiwei Feng, Xiaodong Wang, Guang Cao, Hui Chen, Peng Liu, Haifeng Xu, Qinzong Gao, Renjie Yang, Liang Xu, Xu Zhu Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Interventional Therapy, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xu Zhu, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Interventional Therapy, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China, Tel + 86-10-8819-6059, Email drzhuxu@163.comPurpose: Recently, hepatic arterial infusion chemotherapy (HAIC) has also gained popularity for hepatocellular carcinoma (HCC). Several studies have compared HAIC and Transarterial chemoembolization (TACE). However, comparisons between TACE plus HAIC and HAIC are rarely reported. Here, we evaluated the performance of HepaSphere DEB-TACE combined with HAIC (Hepa-HAIC) compared to HAIC in patients with advanced HCC.Patients and Methods: In this retrospective study, we enrolled 167 patients diagnosed with advanced HCC and treated at Peking University Cancer Hospital from May 2018 to May 2022. The cohort comprised 74 patients who received HepaSphere DEB-TACE combined with HAIC-FOLFOX (Hepa-HAIC) and 93 patients who received HAIC-FOLFOX. Over 60% of patients received prior treatments. To avoid selection bias, propensity score matching was applied to the efficacy and safety analyses. The primary endpoints are progression-free survival (PFS) and overall survival (OS); the secondary endpoints include objective response rate (ORR), disease control rate (DCR), and safety.Results: Propensity-matching yielded 48 pairs, and group baselines were almost equal after matching. Median PFS and median OS were both higher in the matched Hepa-HAIC cohort (median PFS: 8.9 vs 5.8 months, p = 0.035; median OS: 22.4 vs 9.5 months, p = 0.027), which was consistent with pre-matching analysis. The ORR in the Hepa-HAIC and HAIC cohorts was 75.0% and 37.5%, respectively; the DCR was 93.8% after Hepa-HAIC and 81.3% after HAIC. There was no treatment-related death. Grade 3– 4 ALT elevation was more frequent in the Hepa-HAIC group (33.3% vs 8.3%, p = 0.003), while vomiting was more frequent in the HAIC group (29.2% vs 12.5%, p = 0.084).Conclusion: The Hepa-HAIC group is superior to the HAIC group in metrics of PFS, OS, ORR, and DCR, which indicates the combination of HepaSphere DEB-TACE and HAIC may lead to improved outcomes with a comparable safety profile in advanced HCC.Keywords: transarterial chemoembolization, advanced hepatocellular carcinoma, hepatic arterial infusion chemotherapy, propensity score matching

Simin Liu,1,2 Xiu Zhou,1,2 Huiying Jie,1,2 Zetong Zheng,1,2 Bing Cai,1,2 Qingyun Mai,1– 3 Canquan Zhou1– 3 1Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, People’s Republic of China; 3Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, People’s Republic of ChinaCorrespondence: Canquan Zhou, Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-Sen University, No. 1 Zhongshan Second Road, Guangzhou, 510080, People’s Republic of China, Fax +86 87330736, Email zhoucanquan@mail.sysu.edu.cnPurpose: To determine the impact of polycystic ovary syndrome on in vitro fertilization/intracytoplasmic sperm injection and embryo transfer outcomes while analyzing the influencing factors.Patients and Methods: A retrospective cohort study comprised 4839 patients who underwent their first cycle of IVF/ICSI treatment from January 2016 to December 2021. Cumulative pregnancy rates, cumulative live birth rates, and late miscarriage rates compared between the PCOS group and control group. Subgroup analysis and binary regression were used to analyze the influence of BMI on clinical outcomes among individuals diagnosed with PCOS.Results: Non-obese PCOS patients exhibited higher cumulative pregnancy rates, cumulative live birth rates, and late miscarriage rates compared to the control group with the normal BMI population (84.7% vs71.2%, P < 0.001; 74.1% vs 61.6%, P < 0.001; 4.1% vs 2.0%, P = 0.002), but there was no significant difference in early miscarriage rates between the two groups.Conclusion: Non-obese PCOS patients demonstrated a notably higher cumulative live birth rate but also a higher risk of late miscarriage compared to non-PCOS females with a normal BMI.Keywords: body mass index, cumulative live birth rate, in vitro fertilization, intracytoplasmic sperm injection, late miscarriage, polycystic ovary syndrome

Wenjuan Meng,1,&ast; Qingxia Guo,2 Gaoyan Tang,1 Guiyan Han,3 Guikai Ma,1 Qingyun Zhang,1 Rui Li,1 Shuzhen Liu,1,&ast; Guohua Yu1 1Department of Oncology, Weifang People’s Hospital (The First Affiliated Hospital of Shandong Second Medical University), Weifang, Shandong, 261041, People’s Republic of China; 2Department of Oncology, Junan People’s Hospital, Junan, Shandong, 276600, People’s Republic of China; 3Department of Pathology, Weifang People’s Hospital (The First Affiliated Hospital of Shandong Second Medical University), Weifang, Shandong, 261041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guohua Yu, Department of Oncology, Weifang People’s Hospital (The First Affiliated Hospital of Shandong Second Medical University), Weifang, Shandong, 261041, People’s Republic of China, Email ghyry@126.comAbstract: Thyroid metastases secondary to triple-negative breast cancer are sporadic. Diagnosis usually requires fine needle aspiration biopsy (FNAB) and immunohistochemistry. There are no treatment guidelines for this type of cancer, and to date, reports of chemotherapy combined with immunotherapy in thyroid metastases are very rare. Here, we first report the effectiveness of anti-PD-1 inhibitor in combination with chemotherapy for the treatment of metastatic thyroid cancer secondary to advanced triple-negative breast cancer with high expression of programmed cell death ligand 1 (PD-L1). Following six cycles of albumin paclitaxel (400mg d1/21 days) plus PD-1 antibody inhibitor (Sindilizumab 200mg d1/21 days), the patient experienced significant relief of neck swelling and obstructive feeding, both the thyroid metastases and the right breast lesion regressed completely following six cycles of treatment. Chemotherapy combined with immunotherapy may provide a new direction for unresectable advanced thyroid metastases.Keywords: thyroid metastases, triple-negative breast cancer, albumin paclitaxel, anti-PD-1 inhibitor, effectiveness

Jingchao Jia,1,2,&ast; Jing Yang,3,&ast; Leimin Qian,2 Biao Zhou,2 Xiaodong Tang,2 Shuanghai Liu,2 Li Wu,4 Jifeng Chen,5 Yuting Kuang1 1Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of General Surgery, Jiangyin Hospital Affiliated to Nantong University, Wuxi, People’s Republic of China; 3Jiangnan University Medical Center, Wuxi, People’s Republic of China; 4Department of Pharmaceutics, People’s Hospital of Shanggao, Yichun, People’s Republic of China; 5The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, Jinan University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuting Kuang, Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China, Email yuting_kuang@163.com Jifeng Chen, The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, Jinan University, Guangzhou, People’s Republic of China, Email chenjifeng-1987@163.comIntroduction: Spatiotemporally controlled release of siRNA for anti-tumor therapy poses significant challenges. Near-infrared (NIR) light, known for its exceptional tissue penetration and minimal tissue invasiveness, holds promise as a viable exogenous stimulus for inducing controlled siRNA release in vivo. However, the majority of light-responsive chemical bonds exhibit absorption wavelengths in the ultraviolet (UV) or short-wavelength visible light range.Methods: To achieve NIR-controlled siRNA release, the study synthesized a UV-sensitive triblock copolymer cRGD-poly(ethylene glycol)-b-poly(aspartic acid ester-5-(2’-(dimethylamino)ethoxy)-2-nitrobenzyl alcohol)-b-polyphenylalanine, abbreviated as cRGD-PEG-PAsp(EDONB)-PPHE. This copolymer is composed of a cRGD-capped PEG block (cRGD-PEG), a poly(aspartate) block modified with cationic moieties through UV-cleavable 2-nitrobenzyl ester bonds [PAsp(EDONB)], and a hydrophobic polyphenylalanine block (PPHE). The cationic amphiphilic polymer cRGD-PEG-PAsp(EDONB)-PPHE can assemble with hydrophobic upconversion nanoparticles (UCNPs) to form a cationic micelle designated as T-UCNP, which subsequently complexes with siRNA to create the final nanopolyplex T-si/UCNP. siRNA-PLK1 was employed to prepare T-PLK1/UCNP nanopolyplex for anti-tumor therapy.Results: T-PLK1/UCNP not only exhibited outstanding tumor cell targeting through cRGD modification but also achieved 980 nm NIR-controlled PLK1 gene silencing. This was achieved by utilizing the encapsulated UCNPs to convert NIR into UV light, facilitating the cleavage of 2-nitrobenzyl ester bonds. As a result, there was a significant suppression of tumor growth.Conclusion: The UCNPs-encapsulated nanopolyplex T-si/UCNP, capable of co-delivering siRNA and UCNPs, enables precise NIR-controlled release of siRNA at the tumor site for cancer RNAi therapy. This nanopolyplex can enhance the controllability and safety of RNAi therapy for tumors, and it also holds the potential to serve as a platform for achieving controlled release and activation of other drugs, such as mRNA and DNA.Keywords: NIR-controlled siRNA release, nanopolyplex, UCNPs, anti-tumor therapy

Shanyu Liu,1,2,&ast; Xiaolin Hou,3,&ast; Min Shi,1 Yuling Shen,1,2 Zhaoying Li,1,2 Zhenzhu Hu,1,2 Dongdong Yang1 1Department of Neurology, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Department of Neurosurgery, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongdong Yang, Department of Neurology, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, No. 39, Twelve Bridges Road, Chengdu, Sichuan Province, 610075, People’s Republic of China, Tel/Fax +86 028-87783481, Email dongdongyang2020@163.comPurpose: Previous studies have reported mixed results regarding the importance of cortical abnormalities in patients with migraines. However, cortical sulci, as a component of the cerebral cortex, have not been specifically investigated in migraine patients. Therefore, we aim to evaluate alterations in cortical sulcal morphology among patients with chronic migraine (CM), episodic migraine (EM), and healthy controls (HCs).Patients and Methods: In this cross-sectional study, structural magnetic resonance images were acquired from 35 patients with CM, 35 with EM, and 35 HCs. Cortical sulci were identified and reconstructed using the BrainVisa 5.0.4 software. We focused on regions involved in pain processing in which abnormal cortical structure were identified in previous neuroimaging studies. Morphometric analysis was performed to calculate sulcal parameters including mean depth, cortical thickness, and opening width. Partial correlation analyses of clinical characteristics and sulcal parameters were performed for CM, EM and the combined migraine (CM + EM) groups.Results: In comparison with HCs, both CM and EM groups showed increased opening width in bilateral insula. In comparison with HC and EM groups, CM patients showed increased cortical thickness in bilateral superior postcentral sulcus, bilateral median frontal sulcus and left superior parietal sulcus, as well as increased mean depth in the left anterior callosomarginal fissure and decreased mean depth in bilateral superior frontal sulcus and left median frontal sulcus. Migraine frequency and disease duration were both correlated with cortical thickness in bilateral superior postcentral sulcus.Conclusion: Abnormal sulcal morphometry primarily affected areas associated with pain processing in patients with migraine, with CM exhibiting more extensive abnormalities in areas related to sensory and affective processing. These changes may contribute to understanding the pathology of EM and CM.Keywords: sulcal morphometry, mean depth, cortical thickness, opening width, chronic migraine, episodic migraine

Yu Pu,&ast; Xiuxiu Zhou,&ast; Di Zhang, Yu Guan, Yi Xia, Shiyuan Liu, Li Fan Department of Radiology, Second Affiliated Hospital of PLA Naval Medical University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shiyuan Liu; Li Fan, Department of Radiology, Second Affiliated Hospital of Naval Medical University, No. 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Tel +86 21 81886012 ; +86 21 81886011, Fax +86 21 63587668, Email radiology_cz@163.com; fanli0930@163.comPurpose: To explore the morphological alterations in small pulmonary vessels in populations at high risk for chronic obstructive pulmonary disease (COPD) and smokers based on multiple computed tomography (CT) quantitative parameters.Patients and Methods: A total of 1969 Three Major Chest Diseases Screening Study participants with available demographic data and smoking history who underwent low-dose chest CT from 2018 to 2020 were included. All subjects were divided into normal, high risk for COPD, and COPD groups according to their pulmonary function test (PFT) results. Furthermore, the three groups were further subdivided into never-smokers, current smokers, and former smokers subgroups according to their smoking history. Quantitative parameters, such as the number, area at 6 mm~24 mm subpleura and volume of small pulmonary vessels, were extracted by computer software. Differences in small pulmonary vessel parameters among the groups were compared using two-way ANOVA.Results: The number, area at 6 mm~24 mm subpleura and volume of small pulmonary vessels in the group at high risk for COPD were lower than those in the normal group (P< 0.05). The number, area at 6 mm~24 mm subpleura and volume of small pulmonary vessels in the COPD group were higher than those in the normal group (P< 0.05). The number, area of small pulmonary vessels at 6 mm~12 mm subpleura in current smokers with high risk for COPD were higher than those in former smokers with high risk for COPD (P< 0.05).Conclusion: The number, area, and volume of small pulmonary vessels in populations at high risk for COPD were decreased. Smoking cessation may impede structural changes in small pulmonary vessels in populations at high risk for COPD.Keywords: chronic obstructive pulmonary disease, computed tomography, pulmonary vascular structure, quantitative analysis, smoking

Guang Chen,1,&ast; Caohua Lv,2,&ast; Qing Nie,3 Xin Li,1 Yinyi Lv,1 Guoyan Liao,1 Shuangchun Liu,4 Weiwei Ge,2 Jinguang Chen,1 Yunting Du5 1Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, 318000, People’s Republic of China; 2Department of Dermatology, Taizhou Second People’s Hospital, Taizhou, 317200, People’s Republic of China; 3Weifang Centers for Disease Control and Prevention, Weifang, 261061, People’s Republic of China; 4Municipal Hospital Affiliated to Medical School of Taizhou University, Taizhou, 318000, People’s Republic of China; 5Department of Laboratory Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, 110042, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinguang Chen; Yunting Du, Tel/Fax +86 576 88661988, Email tongly0422@126.com; m15840557769@163.comBackground: The traditional Matricaria chamomilla L. has been used to treat dermatitis for thousands of years. Due to emerging trends in alternative medicine, patients prefer natural remedies to relieve their symptoms. Therefore, finding safe and effective plant medicines for topical applications on the skin is an important treatment strategy for dermatologists. German chamomile (Matricaria chamomilla L.) from the Compositae family is a famous medicinal plant, often known as the “star of medicinal species.”However, the function of Matricaria chamomilla essential oil on skin inflammation has not been thoroughly examined in earlier research.Methods: GC-MS analyzed the components of MCEO, and this study explored the anti-inflammation effects of MCEO on psoriasis with network pharmacological pathway prediction. Following this, we used clinical samples of psoriasis patients to confirm the secretory characteristic of relative inflammatory markers. The therapeutic effect of MCEO on skin inflammation was detected by examination of human keratinocytes HaCaT. At the same time, we prepared imiquimod-induced psoriatic-like skin inflammation in mice to investigate thoroughly the potential inhibition functions of MCEO on psoriatic skin injury and inflammation.Results: MCEO significantly reduced interleukin-22/tumor necrosis factor α/lipopolysaccharide-stimulated elevation of HaCaT cell inflammation, which was correlated with downregulating PI3K/Akt/mTOR and p38MAPK pathways activation mediated by MCEO in HaCaT cells treated with IL-22/TNF-α/LPS. Skin inflammation was evaluated based on the PASI score, HE staining, and relative inflammatory cytokine levels. The results showed that MCEO could significantly contribute to inflammatory skin disease treatment.Conclusion: MCEO inhibited inflammation in HaCaT keratinocytes induced by IL-22/TNF-α/LPS, the potential mechanisms associated with inhibiting excessive activation and crosstalk between PI3K/Akt/mTOR and p38MAPK pathways. MCEO ameliorated skin injury in IMQ-induced psoriatic-like skin inflammation of mice by downregulating the levels of inflammatory cytokines but not IL-17A. Thus, anti-inflammatory plant drugs with different targets with combined applications were a potential therapeutic strategy in psoriasis.Keywords: Matricaria chamomilla, essential oil, psoriasis, HaCaT, IMQ, mouse

Linyuan Gui,1,&ast; Qingyuan Ye,2,&ast; Lu Yu,3 Geng Dou,1 Yang Zhou,1 Yang Liu,4 Yanqi Zhang,5 Xiaoshan Yang,1,6 Fang Jin,5 Shiyu Liu,1 Yan Jin,1 Lili Ren1 1State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 2State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Digital Dentistry Center, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 3Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, 250012, People’s Republic of China; 4Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 5State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 6Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lili Ren; Yan Jin, State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China, Email lanyangddgy@qq.com; yanjin@fmmu.edu.cnBackground: Osteoporosis is a highly prevalent disease that causes fractures and loss of motor function. Current drugs targeted for osteoporosis often have inevitable side effects. Bone marrow mesenchymal stem cell (BMSCs)-derived apoptotic extracellular vesicles (ApoEVs) are nanoscale extracellular vesicles, which has been shown to promote bone regeneration with low immunogenicity and high biological compatibility. However, natural ApoEVs cannot inherently target bones, and are often eliminated by macrophages in the liver and spleen. Thus, our study aimed to reconstruct ApoEVs to enhance their bone-targeting capabilities and bone-promoting function and to provide a new method for osteoporosis treatment.Methods: We conjugated a bone-targeting peptide, (Asp-Ser-Ser)6 ((DSS)6), onto the surface of ApoEVs using standard carbodiimide chemistry with DSPE-PEG-COOH serving as the linker. The bone-targeting ability of (DSS)6-ApoEVs was determined using an in vivo imaging system and confocal laser scanning microscopy (CLSM). We then loaded ubiquitin ligase RING finger protein146 (RNF146) into BMSCs via adenovirus transduction to obtain functional ApoEVs. The bone-promoting abilities of (DSS)6-ApoEVs and (DSS)6-ApoEVsRNF146 were measured in vitro and in vivo.Results: Our study successfully synthesized bone-targeting and gained functional (DSS)6-ApoEVsRNF146 and found that engineered ApoEVs could promote osteogenesis in vitro and exert significant bone-targeting and osteogenesis-promoting effects to alleviate osteoporosis in a mouse model.Conclusion: To promote the bone-targeting ability of natural ApoEVs, we successfully synthesized engineered ApoEVs, (DSS)6-ApoEVsRNF146 and found that they could significantly promote osteogenesis and alleviate osteoporosis compared with natural ApoEVs, which holds great promise for the treatment of osteoporosis. Keywords: osteoporosis, mesenchymal stem cells, apoptotic extracellular vesicles, bone-targeting, bone regeneration

Jie Cui,1– 4,&ast; Hongbin Wang,5,6,&ast; Shiyao Liu,1– 4 Yiming Zhao1– 4 1Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China; 2National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China; 3NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China; 4Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215006, People’s Republic of China; 5Department of Emergency, Jiangyin Hospital of Traditional Chinese Medicine, Wuxi, 214400, People’s Republic of China; 6Department of Intensive Care Unit, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yiming Zhao, Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China, Tel +86-512-67781379, Fax +86-512-65113556, Email zhaoyimingbox@163.comBackground: Spontaneous intracerebral hemorrhage (ICH) is a subtype of stroke leading to high rates of morbidity and mortality in adults. Recent studies showed that immune and inflammatory responses might play essential roles in secondary brain injury. The purpose of this article was to provide a reference for further therapeutic strategies for ICH patients.Methods: GSE206971 and GSE216607 datasets from the gene expression omnibus (GEO) database were used to screen the highly immune-related differentally expressed genes (IRDEGs). We used the CIBERSORT algorithm to assess the level of immune signatures infiltration and got the possible function of IRDEGs which was analyzed through Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Protein-protein interaction (PPI) networks and six hub genes were identified in the Cytoscape plug-in. GSVA algorithm was performed to evaluate the potential pathways of six hub genes in ICH samples. The expression level of IL-7R chosen from six hub genes was further validated by Western blotting. The cell models of ICH were established for the research of IL-7/IL-7R signaling way.Results: A total of six hub genes (ITGAX, ITGAM, CCR2, CD28, SELL, and IL-7R) were identified. IL-7R was highly expressed in the mice ICH group, as shown by immunoblotting. Next, we constructed ICH cell models in RAW264.7 cells and BV2 cells. After treatment with IL-7, iNOS expression (M1 marker) was greatly inhibited while Arg-1(M2 marker) was enhanced, and it might function via the JAK3/STAT5 signaling pathway.Conclusion: The hypothesis is proposed that the IL-7/IL-7R signaling pathway might regulate the inflammatory process following ICH by regulating microglia polarization. Our study is limited and requires more in-depth experimental confirmation.Keywords: immune infiltration, intracerebral hemorrhage, CIBERSORT algorithm, IL-7 receptor

Xian Ding,1,&ast; Wenqi Liang,2,&ast; Hongjuan Xia,1,&ast; Yuee Liu,2 Shuxiong Liu,1 Xinyu Xia,1 Xiaoli Zhu,1 Yongyan Pei,3 Dewen Zhang4 1Department of Emergency, Third Affiliated Hospital of Naval Medical University, Shanghai, People’s Republic of China; 2Department of Emergency, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China; 3School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan, People’s Republic of China; 4Longhua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongyan Pei, School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, No. 9-13, Zhongshan Campus, No. 13, Changmingshui Avenue, Wuguishan, Zhongshan City, Guangdong Province, People’s Republic of China, Email peiyongyan@gdpu.edu.cn Dewen Zhang, Longhua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New Area, Shanghai, People’s Republic of China, Email zhangdewen120@hotmail.comBackground: Sepsis was a high mortality and great harm systemic inflammatory response syndrome caused by infection. lncRNAs were potential prognostic marker and therapeutic target. Therefore, we expect to screen and analyze lncRNAs with potential prognostic markers in sepsis.Methods: Transcriptome sequencing and limma was used to screen dysregulated RNAs. Key RNAs were screened by correlation analysis, lncRNA-mRNA co-expression and weighted gene co-expression network analysis. Immune infiltration, gene set enrichment analysis and gene set variation analysis were used to analyze the immune correlation. Kaplan–Meier curve, receiver operator characteristic curve, Cox regression analysis and nomogram were used to analyze the correlation between key RNAs and prognosis. Sepsis model was established by lipopolysaccharide-induced HUVECs injury, and then cell viability and migration ability were detected by cell counting kit-8 and wound healing assay. The levels of apoptosis-related proteins and inflammatory cytokines were detected by RT-qPCR and Western blot. Reactive Oxygen Species and superoxide dismutase were detected by commercial kit.Results: Fourteen key differentially expressed lncRNAs and 663 key differentially expressed genes were obtained. And these lncRNAs were closely related to immune cells, especially T cell activation, immune response and inflammation. Subsequently, Subsequently, lncRNA PRKCQ-AS1 was identified as the regulator for further investigation in sepsis. RT-qPCR results showed that PRKCQ-AS1 expression was up-regulated in clinical samples and sepsis model cells, which was an independent prognostic factor in sepsis patients. Immune correlation analysis showed that PRKCQ-AS1 was involved in the immune response and inflammatory process of sepsis. Cell function tests confirmed that PRKCQ-AS1 could inhibit sepsis model cells viability and promote cell apoptosis, inflammatory damage and oxidative stress.Conclusion: We constructed immune-related lncRNA-mRNA regulatory networks in the progression of sepsis and confirmed that PRKCQ-AS1 is an important prognostic factor affecting the progression of sepsis and is involved in immune response.Keywords: sepsis, immune-related lncRNA, lncRNA-mRNA, PRKCQ-AS1, prognosis and progress