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Rescuing seal pups is an important conservation action for spotted seals Phoca largha. Gut microbiota are directly associated with host health and diet metabolism. Therefore, knowledge gained from gut microbiota variations of spotted seal pups held in captivity after rescue can help formulate comprehensive rescue plans for the future. In this study, we collected feces from a rescued spotted seal pup every 3 d during the rescue process. Fecal bacterial communities were measured by high-throughput sequencing based on 16S rRNA amplification. Firmicutes were the most dominant bacteria, comprising >70% of the total gut microbiota. Moreover, differences in fecal bacterial communities of the rescued spotted seal pup between rescue and release were compared. At release, the abundances of 2 potential bacteria related to gut health, Blautia producta and Cetobacterium somerae, were remarkably lower, while Clostridium perfringens, a key mammalian pathogen, was significantly higher in the feces of the released pup. Moreover, the pup experienced a bout of diarrhea during its time in captivity, which resulted in a momentary change in its gut microbiota. Fusobacterium was recognized as a potential causative pathogen for the diarrhea. This study contributes to our understanding of gut microbiota variations in spotted seal pups during the rescue period.

Yuling Liang,1,* Yuqing Xie,1,* Xiaoli Liu,1 Lihua Yu,1 Huiwen Yan,1 Zimeng Shang,1 Yuan Wu,1 Xue Cai,2 Wanxin Shi,2 Juan Du,3 Zhiyun Yang1 1Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 2Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 3Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China*These authors contributed equally to this workCorrespondence: Juan Du, Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China, Email duj656@163.com Zhiyun Yang, Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China, Tel +86-10-84322148, Email yangzhiyun2016@163.comPurpose: Traditional Chinese medicine (TCM) therapy is an important means to treat hepatocellular carcinoma (HCC), Astragalus (Latin name: Hedysarum Multijugum Maxim; Chinese name: Huangqi, HQ) and Atractylodes (Latin name: Atractylodes Macrocephala Koidz; Chinese name: Baizhu, BZ) (HQBZ), a classic herb pair, is often used in combination to HCC. However, the main components and potential mechanisms of HQBZ therapy in HCC remain unclear. This study aimed to identify the potential active ingredients and molecular mechanisms of action of HQBZ in HCC treatment.Methods: The HQBZ-Compound-Target-HCC network and HQBZ-HCC transcriptional regulatory network were constructed to screen the core active compound components and targets of HQBZ therapy for HCC. Molecular docking techniques are used to verify the stability of binding core active compound components to targets. GO and KEGG enrichment analysis were used to explore the signaling pathway of HQBZ in HCC treatment, the mechanism of HQBZ treatment of HCC was verified based on in vivo H22 tumor bearing mice and in vitro cell experiments.Results: Network pharmacology and molecular docking studies showed that HQBZ treatment of HCC was related to the targeted regulation of IL-6 and STAT3 by the active compound biatractylolide, KEGG pathway enrichment analysis suggest that HQBZ may play a role in the treatment of HCC through IL-6/STAT3 signaling pathway. In vitro experiment results proved that HQBZ could regulate IL-6/STAT3 signaling pathway transduction on CD8+T cells, inhibit CD8+T cell exhaustion and restore the function of exhausted CD8+T cells. In vivo experiment results proved that HQBZ can regulate IL-6/STAT3 signaling pathway transduction in H22 liver cancer model mouse tumor tissue, increased the proportion of tumor infiltrating CD8+T cells.Conclusion: This study found that HQBZ may play a therapeutic role in HCC by targeting IL-6 and STAT3 through biatractylolide, its mechanism of action is related to regulating IL-6/STAT3 signaling pathway, reversing T cell failure and increasing tumor infiltration CD8+T cells.Keywords: Astragalus–Atractylodes herb pair, hepatocellular carcinoma, IL-6/STAT3 signaling pathway, molecular docking, network pharmacology

Juan Du,1,* Li-Li Shi,2,* Wei-Wei Jiang,3 Xue-Ai Liu,3 Xin-Hong Wu,3 Xiang-Xiang Huang,3 Ming-Wei Huo,3 Ling-Zhi Shi,3 Jingjian Dong,2 Xiaohong Jiang,2 Renyu Huang,4 Qing-Ri Cao,3 Wenzhou Zhang1 1Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, People’s Republic of China; 2College of Medicine, Jiaxing University, Jiaxing, People’s Republic of China; 3College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, People’s Republic of China; 4College of Social Science, Soochow University, Institute of Culture and Tourism Development, Soochow University, Suzhou, 215123, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenzhou Zhang, Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, People’s Republic of China, Email hnzzzwzx@sina.com Qing-Ri Cao, College of Pharmaceutical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou Industrial Park, Jiangsu, 215123, People’s Republic of China, Email qrcao@suda.edu.cnBackground: The commercial docetaxel (DTX) formulation causes severe side effects due to polysorbate 80 and ethanol. Novel surfactant-free nanoparticle (NP) systems are needed to improve bioavailability and reduce side effects. However, controlling the particle size and stability of NPs and improving the batch-to-batch variation are the major challenges.Methods: DTX-loaded bovine serum albumin nanoparticles (DTX-BSA-NPs) were prepared by a novel thermal-driven self-assembly/microfluidic technology. Single-factor analysis and orthogonal test were conducted to obtain the optimal formulation of DTX-BSA-NPs in terms of particle size, encapsulation efficiency (EE), and drug loading (DL). The effects of oil/water flow rate and pump pressure on the particle size, EE, and DL were investigated to optimize the preparation process of DTX-BSA-NPs. The drug release, physicochemical properties, stability, and pharmacokinetics of NPs were evaluated.Results: The optimized DTX-BSA-NPs were uniform, with a particle size of 118.30 nm, EE of 89.04%, and DL of 8.27%. They showed a sustained release of 70% over 96 hours and an increased stability. There were some interactions between the drug and excipients in DTX-BSA-NPs. The half-life, mean residence time, and area under the curve (AUC) of DTX-BSA-NPs increased, but plasma clearance decreased when compared with DTX.Conclusion: The thermal-driven self-assembly/microfluidic combination method effectively produces BSA-based NPs that improve the bioavailability and stability of DTX, offering a promising alternative to traditional formulations. Keywords: DTX-BSA nanoparticles, thermal-driven self-assembly, microfluidic technology, in-vitro release, pharmacokinetics

Jun Du,1 Qing-long Gu,1 Ying-xia Lu,1 Lei Zhang,2 Xiao-jun Zhan,1 Zhan Wang1 1Department of Otolaryngology, Head and Neck Surgery, Children’s Hospital Capital Institute of Pediatrics, Beijing, 100000, People’s Republic of China; 2Department of Hematopathology, Children’s Hospital Capital Institute of Pediatrics, Beijing, 100000, People’s Republic of ChinaCorrespondence: Qing-long Gu, Department of Otolaryngology, Head and Neck Surgery, Children’s Hospital Capital Institute of Pediatrics, No. 2 Yabao Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86-13810091816, Email qinglonggugql@126.comObjective: To evaluate the safety and feasibility of tonsillectomy and/or adenoidectomy (T&A) in pediatric patients with prolonged activated partial thromboplastin time (APTT) and coagulation factor deficiency.Methods: A prospective study was admitted to the children undergoing T&A at our institution between October 2019 and January 2020, specifically focusing on preoperative coagulation function. Within this group, we identified 5 patients exhibiting prolonged APTT and coagulation factor deficiencies, constituting the experimental group, and 10 patients matched by gender and age with normal blood coagulation function were selected as the control group. Comparative analyses between the two groups were conducted, focusing on surgical duration, intraoperative bleeding volume, duration of hospital stay, and postoperative complications such as active bleeding across the groups. At the six-month postoperative mark, a reassessment of coagulation functions and factor assays was conducted within the experimental group.Results: No statistically significant differences were discovered in terms of surgical duration or bleeding volume when comparing the experimental subgroups with their respective control counterparts. Furthermore, there were no incidences of postoperative active bleeding observed in any of the groups. Notably, postoperative APTT values (32.7 ± 1.7s) exhibited a significant disparity compared to preoperative levels (43.7 ± 1.8s, p < 0.01). Coagulation factors demonstrated normalization, evidenced by a significant difference in postoperative Factor XII levels (40.2 ± 5.4%) compared to preoperative levels (63.1 ± 5.9%, p < 0.01).Conclusion: Prolonged APTT with FXII factor deficiency does not show a significant bleeding tendency and is not a contraindication for T&A surgery. Post T&A surgery, children with abnormal coagulation function and deficient clotting factors show significant improvement compared to pre-surgery. It is important to consider that chronic inflammation in adenoids and tonsils may contribute to the prolongation of APTT and the manifestation of Factor XII deficiency.Keywords: adenoidectomy, children, factor XII deficiency, prolonged APTT, tonsillectomy

Hai Xu,1 Conghui Hao,1 Xinxin Wang,2 Jingjing Du,1 Tianyu Zhang,1 Xiaobao Zhang2,3 1Department of Anesthesiology, Graduate Training Base of Lianyungang First People’s Hospital of Jinzhou Medical University, Lianyungang, Jiangsu, People’s Republic of China; 2Department of Anesthesiology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, People’s Republic of China; 3Department of Anesthesiology, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, People’s Republic of ChinaCorrespondence: Xiaobao Zhang, Department of Anesthesiology, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, People’s Republic of China, Email hotdog100@163.comBackground: Magnesium sulfate, an intravenous adjuvant, has recently attracted immense attention in multimodal analgesia. Previous studies confirmed the crucial role of magnesium sulfate in postoperative pain and nociceptive hypersensitivity. However, the effect of magnesium sulfate in multimodal analgesia on the quality of recovery (QoR) for elderly patients has not been thoroughly studied. Therefore, the present experiment aimed to investigate the effect of continuous intravenous magnesium sulfate on the quality of postoperative recovery in elderly patients undergoing total knee arthroplasty (TKA).Patients and Methods: In this study, a total of 148 patients scheduled to undergo unilateral total knee arthroplasty were randomized into a magnesium sulfate group (Group M, n=68) and a control group (Group C, n=66) using a double-blind, randomized controlled trial. Before induction of anesthesia, Group M received intravenous magnesium sulfate (40 mg/kg) for 15 min, followed by a continuous infusion (15 mg/kg) until the end of the procedure. In the same manner, Group C received an infusion of the same amount of isotonic saline using the same method as the Group M.Results: Compared with Group C, Group M had significantly better QoR-15 scores on postoperative day 1(POD1) than Group C (P < 0.05). Analysis of the dimensions of QoR-15 scores indicated that Group M exhibited notably reduced levels of pain, and higher levels of emotional state and physical comfort than Group C (P < 0.05). Furthermore, Group C had significantly higher numerical rating scale (NRS) scores at POD1 than Group M (P < 0.05).Conclusion: For elderly patients undergoing knee arthroplasty, magnesium sulfate can be used as an adjuvant in a multimodal analgesic regimen to reduce early postoperative pain and improve the quality of early postoperative recovery.Keywords: magnesium sulfate, quality of recovery, postoperative pain, multimodal analgesic regimen, total knee arthroplasty

Nana Zhou,1,&ast; Chaoqin Guo,1,&ast; Jingyang Du,1 Xu Zhang,1 Qiuran Xu,2 Xiaoliang Zheng,3 Linglan Tu3 1School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, 310053, People’s Republic of China; 2The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 3School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, 310053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linglan Tu; Xiaoliang Zheng, School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, Zhejiang, 310053, People’s Republic of China, Tel +86-571-88215564 ; +86-571-88215569, Email tulinglan@hmc.edu.cn; Zhengxl@hmc.edu.cnPurpose: Colorectal cancer (CRC) is one of the cancers with high incidence and mortality rates worldwide. In China, there are approximately 400,000 new CRC cases each year, seriously endangering people’s life and health. Transforming growth factor β-stimulated clone 22 domain family, member 2 (TSC22D2) is widely expression in cancers, but the role of TSC22D2 in CRC are still unknown.Methods: Real‑time quantitative PCR (qRT-PCR) and Western blot were applied to determine the TSC22D2 levels. CCK-8, colony formation and transwell assays were used to determine the proliferation and metastasis abilities of CRC cells in vitro. In vivo metastatic potential was assessed using a subcutaneously injected mouse model and. Western-blot and immunoprecipitation experiments were used to study the mechanism of TSC22D2‑mediated metastasis.Results: We found TSC22D2 was deregulated in CRC tissues and cells and implied poor prognosis. Overexpression TSC22D2 significantly promoted CRC cells proliferation and tumorigenicity both in vitro and vivo, whereas knockdown TSC22D2 resulted in the opposite effects. Importantly using a co-immunoprecipitation (co-IP) assay combined with mass spectrometry analysis to identify TSC22D2-interacting acyl-coenzyme A thioesterases 8 (ACOT8), TSC22D2 maintained stability of ACOT8. Overexpression of TCC22D2 in CRC cells can promote the expression of ACOT8 and inhibit the proliferation and metastasis of CRC cells through EMT mechanism, highlighting the possibility of TSC22D2 as a potential target in CRC development.Conclusion: In summary, the present study revealed the inhibitory effect of TSC22D2 on the proliferation of colorectal cancer cells, suggesting that TSC22D2 may be an important tumor suppressor and a potential therapeutic target during colorectal carcinogenesis.Keywords: colorectal cancer, TSC22D2, ACOT8, EMT

Naigeng Wang,1 Fei Li,2 Jing Du,3 Jianhong Hao,1 Xin Wang,2 Yueru Hou,3 Zhenguo Luo1 1Department of Anesthesiology, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 3Second Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of ChinaCorrespondence: Zhenguo Luo, Email luozhenguo@stu.xjtu.edu.cnBackground: This study aims to investigate the protective effect of quercetin against global cerebral ischemia‒reperfusion (GCI/R) injury in rats and elucidate the underlying mechanism.Methods: A GCI/R injury rat model was established using a four-vessel occlusion (4-VO) method. An oxygen–glucose deprivation/reoxygenation (OGD/R) injury model was induced in BV2 cells. The extent of injury was assessed by evaluating neurological deficit scores (NDS) and brain water content and conducting behavioral tests. Pathomorphological changes in the prefrontal cortex were examined. Additionally, the study measured the levels of inflammatory cytokines, the degree of microglial activation and polarization, and the protein expression of Toll-like receptor 4 (TLR4) and TIR-domain-containing adaptor inducing interferon-β (TRIF).Results: Quercetin pretreatment significantly ameliorated neurological impairment, improved learning and memory abilities, and reduced anxiety in rats subjected to GCI/R injury. Furthermore, quercetin administration effectively mitigated neuronal injury and brain edema. Notably, it suppressed microglial activation and hindered polarization toward the M1 phenotype. Simultaneously, quercetin downregulated the expression of TLR4 and TRIF proteins and attenuated the release of IL-1β and TNF-α.Conclusion: This study highlights the novel therapeutic potential of quercetin in alleviating GCI/R injury. Quercetin demonstrates its neuroprotective effects by inhibiting neuroinflammation and microglial activation while impeding their transformation into the M1 phenotype through modulation of the TLR4/TRIF pathway.Keywords: quercetin, cerebral ischemia, neuroprotection, neuroinflammation

Meiju Deng,1,2,&ast; Yongqin Zeng,2,3,&ast; Ying Liu,2 Xiaolei Wang,1,2 Na Chen,1,2 Mengyuan Zhang,1,4– 6 Meiqing Jiang,1,4– 6 Hongxin Zhao,2 Juan Du1,4– 6 1Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 2Clinical Center for HIV/AIDS, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 3Department of Nephrology, The Affiliated Hospital Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of China; 4Beijing Institute of Infectious Diseases, Beijing, 100015, People’s Republic of China; 5National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 6National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing, 100015, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan Du; Hongxin Zhao, Email duj656@ccmu.edu.cn; Drzhao66@ccmu.edu.cnBackground: The aging of the immune system is associated with various diseases. It is worth exploring the changes of the immune system in aging. Previous studies have shown that aged T cells have enhanced expression of co-inhibitory molecules. However, it remains unclear whether aged NK cells exhibit similar characteristics to aged T cells. The objective of our research was to clarify this aspect.Patients and Methods: This study included 98 adults aged 24– 90 years (50 males and 48 females). We detected the subset of peripheral blood NK cells and the expression of various receptors on NK cells among donors of different age groups by flow cytometry. Immune subsets were initially defined by forward and side-scatter characteristics and then staining with the appropriate marker.Results: The absolute number and subset distribution of NK cells were not associated with age. However, CD57 expression and CD69 expression were correlated with age. Furthermore, we found that PD-1 was up-regulated on NK cells in older people, associated with aging, while no such change was observed in other co-inhibitory molecules, including 2B4, CTLA-4, TIM-3, BTLA, CD70, CD39, CD160, and TIGIT. PD-1+ NK cells expressed high levels of CD57 and CD69, indicating PD-1+ NK cells displayed a phenotype of over-activation and aging.Discussion: This study indicated that PD-1+ NK cells were one of the characteristics of NK cells in older people.Conclusion: This study indicated that PD-1+ NK cells were one of the characteristics of NK cells in older people. Those findings provided new ideas to explore the underlying drivers of NK aging.Keywords: PD-1, NK cell, aging, co-inhibitory molecules

Long Lv,1,&ast; Jinghu Du,1,&ast; Daorong Wang,2 Zeqiang Yan2 1Department of General Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, People’s Republic of China; 2Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Daorong Wang; Zeqiang Yan, Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, People’s Republic of China, Tel +13581425716 ; +13597505970, Email 415004128@qq.com; yzqi48959@163.comBackground: Gastric cancer (GC) is a common fatal malignancy. The aim of this study was to explore and validate the tumor-suppressive role and mechanism of Radix Bupleuri in GC.Methods: The active constituents of Radix Bupleuri were screened using TCMSP database. SwissTargetPrediction database was used to predict potential target genes of the compounds. GeneCards, TTD, DisGeNET, OMIM, and PharmGKB databases were used to search for GC-related targets. STRING database and Cytoscape 3.10 software were used for protein–protein interaction network construction and screening of core targets. DAVID database was used for GO and KEGG analyses. Core targets were validated using molecular docking. Cell proliferation and apoptosis were detected using CCK-8 and flow cytometry after GC cells were treated with isorhamnetin. The mRNA and protein expression levels of genes were detected using qRT PCR and Western blot. The metastasis potential of GC cells was evaluated in a nude mouse model.Results: A total of 371 potential targets were retrieved by searching the intersection of Radix Bupleuri and GC targets. Petunidin, 3’,4’,5’,3,5,6,7-Heptamethoxyflavone, quercetin, kaempferol, and isorhamnetin were identified as the main bioactive compounds in Radix Bupleuri. SRC, HSP90AA1, AKT1, and EGFR, were core targets through which Radix Bupleuri suppressed GC. The tumor-suppressive effect of Radix Bupleuri on GC was mediated by multiple pathways, including PI3K-AKT, cAMP, and TNF signaling. The key compounds of Radix Bupleuri had good binding affinity with the core target. Isorhamnetin, a key component of Radix Bupleuri, could inhibit proliferation and metastasis, and induces apoptosis of GC cells. In addition, isorhamnetin could also reduce the mRNA expression of core targets, and the activation of PI3K/AKT pathway.Conclusion: This study identified potential targets and pathways of Radix Bupleuri against GC through network pharmacology and molecular docking, providing new insights into the pharmacological mechanisms of Radix Bupleuri in GC treatment. Keywords: gastric cancer, Radix Bupleuri, network pharmacology, molecular docking

Yunzhi Xiang,&ast; Guanghui Wang,&ast; Baoliang Liu, Haotian Zheng, Qiang Liu, Guoyuan Ma, Jiajun Du Institute of Oncology, Shandong Provincial Hospital, Shandong University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiajun Du, Shandong Provincial Hospital, No. 324 Jingwu Road, Huaiyin District, Jinan, 250000, People’s Republic of China, Email dujiajun@sdu.edu.cnBackground: In recent years, the immunotherapy of lung adenocarcinoma has developed rapidly, but the good therapeutic effect only exists in some patients, and most of the current predictors cannot predict it very well. Tumor-infiltrating macrophages have been reported to play a crucial role in lung adenocarcinoma (LUAD). Thus, we want to build novel molecular markers based on macrophages.Methods: By non-negative matrix factorization (NMF) algorithm and Cox regression analysis, we constructed macrophage-related subtypes of LUAD patients and built a novel gene signature consisting of 12 differentially expressed genes between two subtypes. The gene signature was further validated in Gene-Expression Omnibus (GEO) datasets. Its predictive effect on prognosis and immunotherapy outcome was further evaluated with rounded analyses. We finally explore the role of TRIM28 in LUAD with a series of in vitro experiments.Results: Our research indicated that a higher LMS score was significantly correlated with tumor staging, pathological grade, tumor node metastasis stage, and survival. LMS was identified as an independent risk factor for OS in LUAD patients and verified in GEO datasets. Clinical response to immunotherapy was better in patients with low LMS score compared to those with high LMS score. TRIM28, a key gene in the gene signature, was shown to promote the proliferation, invasion and migration of LUAD cell.Conclusion: Our study highlights the significant role of gene signature in predicting the prognosis and immunotherapy efficacy of LUAD patients, and identifies TRIM28 as a potential biomarker for the treatment of LUAD.Keywords: lung adenocarcinoma, macrophage, TRIM28, prognosis, immunotherapy

Yunhong Ren,1,&ast; Yinhao Guo,2,&ast; Jing Tang,2 Ling He,1 Meiling Li,1 Xuemei Huang,1 Qin Lu,1 Baoxia Sun,1 Haixia Feng,1 Huan Liu,1 Juan Du,1 Jun Li1 1Mianyang Key Laboratory of Anesthesia and Neuroregulation, Department of Anesthesiology, Mianyang Central Hospital, Mianyang, Sichuan, 621000, People’s Republic of China; 2Department of Anesthesiology, North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Li; Juan Du, Mianyang Key Laboratory of Anesthesia and Neuroregulation, Department of Anesthesiology, Mianyang Central Hospital, Mianyang, Sichuan, People’s Republic of China, Email lj89199@163.com; 1151941061@qq.comPurpose: This study aimed to investigate the effects of different psychological personalities and pain catastrophizing levels on postoperative analgesia in patients undergoing cesarean section.Patients and Methods: Puerperas who underwent cesarean section at our hospital between January and August 2023 were recruited into the study and assessed using the Eysenck Personality Questionnaire-Revised Short Scale (EPQRSC) and Pain Catastrophizing Scale (PCS). Data on the numerical pain intensity at rest and during activity 24 h after surgery, number and dosage of analgesia pumps, and satisfaction with analgesia were recorded. According to the numerical pain score during activity 24 h post-operation, the patients were divided into the analgesia incomplete group (≥ 4) and control group (< 4). Univariate analysis, Spearman correlation analysis, and binary logistic regression analysis were used to evaluate the influence of personality characteristics and PCS on postoperative analgesia.Results: A total of 778 women were included in the study. The incidence of inadequate analgesia was 89.8%. The satisfaction rate of analgesia was 66.8%. Univariate analysis showed that extraversion; neuroticism; PCS; numbers of previous cesarean delivery; ASA; analgesic satisfaction; and 24-h analgesia pump compressions and dosage were associated with postoperative analgesia after cesarean section (P< 0.05). Using binary logistic regression analysis, the first cesarean section (odds ratio [OR]=0.056, 95% confidence interval [CI]=1.913– 19.174), the number of 24-h analgesic pump compressions (OR=8.464, 95% CI=0.356– 0.604), extraversion (OR=0.667, 95% CI=0.513– 0.866), neuroticism (OR=1.427, 95% CI=1.104– 1.844), and PCS (OR=7.718, 95% CI=0.657– 0.783) were factors affecting postoperative analgesia.Conclusion: The incidence of inadequate analgesia after a cesarean section was high (89.8% on the first day after surgery). Formulating accurate analgesia programs for women undergoing cesarean section with extraversion, neuroticism personality characteristics, and pain catastrophizing behaviors is necessary for improving their postoperative analgesia effects and satisfaction and promoting postpartum comfort.Keywords: aftercare, anesthetics, breast feeding, fear, personal satisfaction, postpartum depression

Wentao Zhong,1– 3,&ast; Qianyu Wang,2,&ast; Xiaofei Shen,4,&ast; Yuan Lv,2,3 Liang Sun,2 Ran An,5 Hongyan Zhu,5 Huiyun Cai,2 Gang Chen,2,3 Aijun Liu,5 Junfeng Du1– 3 1The Second School of Clinical Medicine, Southern Medical University, Guangdong, 510515, People’s Republic of China; 2Department of General Surgery, The 7th Medical Center, Chinese PLA General Hospital, Beijing, 100700, People’s Republic of China; 3Medical Department of General Surgery, The 1st Medical Center, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 4Division of Gastric Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, People’s Republic of China; 5Department of Pathology, the 7th Medical Center, Chinese PLA General Hospital, Beijing, 100700, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aijun Liu, Department of Pathology, The 7th Medical Center, Chinese PLA General Hospital, NO. 5, Nanmen Cang, Beijing, 100700, People’s Republic of China, Email aliu301@126.com Junfeng Du, Department of General Surgery, the 7th Medical Center, Chinese PLA General Hospital, NO. 5, Nanmen Cang, Beijing, 100700, People’s Republic of China, Email dujf66@126.comPurpose: To demonstrate the intrinsic association of Neutrophil extracellular traps (NETs) with outcome and neoadjuvant therapy response of locally advanced rectal cancer (LARC), and the mechanisms.Patients and Methods: We enrolled 240 patients with LARC who underwent surgery without neoadjuvant therapy in two independent sets (training and validation), and 153 patients who received neoadjuvant therapy with biopsy followed by surgery. Immunohistochemistry, immunofluorescence staining and bioinformatics analysis were performed in formalin-fixed paraffin-embedded sections. NETs were identified by costaining for myeloperoxidase and citrullinated histone H3.Results: NETs were associated with recurrence-free survival in the surgical training and validation sets. High-NET density predicted poor postoperative survival of patients with LARC. Multivariate analysis identified NETs, TNM stage, and neutrophil-to-lymphocyte ratio as independent prognostic factors for recurrence-free survival. Low-NETs LARC demonstrated increased CD8+ T cell and lower T regulatory cell infiltration, which indicated a tumor immune microenvironment with strong antitumor capacity. High-NET density was associated with epithelial–mesenchymal transition, which is considered to contribute to tumor progression. In the neoadjuvant therapy cohort, high-NET density on biopsy was significantly associated with reduced likelihood of complete/near complete response.Conclusion: NET was an independent prognostic factor in LARC that were associated with patients’ survival, and NET density in pretreatment biopsies was an independent predictive biomarker of response to neoadjuvant therapy. This biomarker may be helpful in predicting survival in LARC with improved accuracy and selecting patients who will respond to neoadjuvant therapy.Keywords: NETs, tumor microenvironment, locally advanced rectal cancer, outcome

Man Li,&ast; Fang Wang,&ast; Xinxin Li, Xiaolan Ding, Juan Du Department of Dermatology, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Wang; Juan Du, Department of Dermatology, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China, Fax +861088325474, Email wfangxixi@sina.com; dujuan223@126.comBackground: Dermoscopic and ultrastructural features of vitiligo-associated leukotrichia (VAL) have not been well studied. This study is aimed at the dermoscopic and ultrastructural features of VAL.Methods: We present a cross-sectional study of VAL-related dermoscopic signs and their relationship with disease stages and duration of leukotrichia. Characteristics of hair surface and finer details including melanosomes, macrofibrils, and remnant nucleus were observed under Electron Microscopy (EM).Results: One hundred and forty samples on distinct sites from 100 patients were collected. Among 75 VAL from the scalp, the prevalence of diameter diversity of leukotrichia (52.6% vs 8.1%), Pohl-Pinkus constrictions (34.2% vs 0), and depigmented hair roots signs (34.2% vs 8.1%) in patients with progressive vitiligo was much higher than that in patients with stable vitiligo (all P< 0.05). The EM result of VAL showed that melanosomes were smaller with vesicles formation, reduced counts, and incomplete shape, and macrofibrils were irregularly arranged with widened spaces and vesicles formation.Limitations: No conclusions about the histopathologic characteristics or dermoscopic-histopathologic correlation of the VAL.Conclusion: The dermoscopic signs of diameter diversity of leukotrichia, Pohl-Pinkus constrictions, and depigmented hair roots are related to progressive vitiligo. The process of melanin synthesis and formation of VAL are impaired at the early stage of VAL under Electron microscopy.Keywords: vitiligo, leukotrichia, dermoscopy, electron microscopy, diameter diversity, Pohl-Pinkus constrictions, melanosomes

Conghui Hao,1 Hai Xu,1 Jingjing Du,1 Tianyu Zhang,1 Xiaobao Zhang,2 Zhibin Zhao,2 Hengfei Luan2 1Department of Anesthesiology, Graduate Training Base of Lianyungang First People’s Hospital of Jinzhou Medical University, Lianyungang, Jiangsu, People’s Republic of China; 2Department of anesthesiology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, The First People’s Hospital of Lianyungang, Lianyungang, Jiangsu, People’s Republic of ChinaCorrespondence: Hengfei Luan, The Affiliated Lianyungang Hospital of Xuzhou Medical University, The First People’s Hospital of Lianyungang, No. 6 East Zhenhua Road, Lianyungang, Jiangsu, People’s Republic of China, Email luanhengfei1027@163.comPurpose: Opioid analgesics may delay discharge and affect postoperative quality of recovery because of their significant adverse effects, such as hyperalgesia, postoperative nausea and vomiting (PONV), shivering and urine retention. We aimed to compare the quality of postoperative recovery (QoR) between patients undergoing laparoscopic cholecystectomy surgeries with opioid-free anesthesia (OFA) and those with opioid-based anesthesia (OA).Patients and Methods: 80 adult patients undergoing laparoscopic cholecystectomy were randomly allocated to an opioid-free anesthesia group (Group OFA) or an opioid-based anesthesia group (Group OA). The primary outcome was the quality of postoperative recovery using QoR-15 scale on postoperative day 1 (POD 1) and 2 (POD 2). The secondary outcomes included the incidence of opioid-related adverse symptoms, perioperative hemodynamic data, duration of post-anesthesia care unit (PACU) stay and duration of extubation, and the incidences of hypotension and bradycardia.Results: A statistically significant difference in total QoR-15 was observed between the two groups on POD 1 and POD 2 (91.00 (90.00, 92.00) vs 113.00 (108.25, 115.00), 106.00 (104.00, 112.00) vs 133.00 (130.00, 135.00), P < 0.001). The incidence of opioid-related symptoms was significantly different between the two groups on POD 1 (P < 0.05). There were between-group differences in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at T3 (P 0.05). There was no difference in heart rate between the two groups at all observed time points, either (P > 0.05).Conclusion: We concluded that the quality of recovery of patients receiving OFA was superior to those receiving OA after laparoscopic cholecystectomy.Keywords: opioid-free anesthesia, opioid-based anesthesia, postoperative recovery, laparoscopic cholecystectomy

Yu Hu,1– 3 Hui Guo,1– 3 Shuai Cheng,1– 3 Junpeng Sun,2,4 Jiaqun Du,2,4 Xiaobang Liu,2,4 Ying Xiong,5 Liqing Chen,6 Chang Liu,3,6 Chao Wu,2,4 He Tian1– 3 1School of Basic Medicine, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People’s Republic of China; 2Liaoning Provincial Collaborative Innovation Center for Medical Testing and Drug Research, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People’s Republic of China; 3Key Laboratory of Medical Tissue Engineering of Liaoning Province, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People’s Republic of China; 4Pharmacy School, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People’s Republic of China; 5Laboratoire Catalyse et Spectrochimie (LCS), Normandie Université, ENSICAEN, UNICAEN, CNRS, Caen, 14050, France; 6Department of Endocrinology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121000, People’s Republic of ChinaCorrespondence: He Tian; Chao Wu, Email tianhe@jzmu.edu.cn; wuchao@jzmu.edu.cnBackground: Oxidative stress induced reactive oxygen species (ROS) and aggregation of amyloid β (Aβ) in the nervous system are significant contributors to Alzheimer’s disease (AD). Cerium dioxide and manganese oxide are known as to be effective and recyclable ROS scavengers with high efficiency in neuroprotection.Methods: A hollow-structured manganese-doped cerium dioxide nanoparticle (LMC) was synthesized for loading Resveratrol (LMC-RES). The LMC-RES were characterized by TEM, DLS, Zeta potential, and X-ray energy spectrum analysis. We also tested the biocompatibility of LMC-RES and the ability of LMC-RES to cross the blood-brain barrier (BBB). The antioxidant effects of LMC-RES were detected by SH-SY5Y cells. Small animal live imaging was used to detect the distribution of LMC-RES in the brain tissue of AD mice. The cognitive abilities of mice were tested by water maze and nesting experiments. The effects of LMC-RES in reducing oxidative stress and protecting neurons was also explored by histological analysis.Results: The results showed that LMC-RES had good sustained release effect and biocompatibility. The drug release rate of LMC-RES at 24 hours was 80.9 ± 2.25%. Meanwhile, LMC-RES could cross the BBB and enrich in neurons to exert antioxidant effects. In Aβ-induced SH-SY5Y cells, LMC-RES could inhibits oxidative stress through the Nrf-2/HO-1 signaling pathway. In AD model mice, LMC-RES was able to reduce ROS levels, inhibit Aβ-induced neurotoxicity, and protect neurons and significantly improve cognitive deficits of AD mice after drug administration.Conclusion: LMC-RES can effectively across the BBB, reduce oxidative stress, inhibit Aβ aggregation, and promote the recovery of neurological function.Keywords: cerium dioxide nanoparticles, manganese, oxidative stress, resveratrol, Alzheimer’s disease

Jingjing Du,1 Yiqing Tao,2 Jiaxing Yang,1 Jiachang Cai,1 Hongwei Zhou,1 Rong Zhang,1 Yanyan Hu1 1Department of Clinical Laboratory, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, People’s Republic of China; 2Department of Orthopedics, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Rong Zhang; Yanyan Hu, Department of Clinical Laboratory, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, 310009, People’s Republic of China, Email zhang-rong@zju.edu.cn; yanyanhu@zju.edu.cnAbstract: Brucellosis is a zoonotic disease caused by Brucella spp., with the highest prevalence found in the northern cities of China. In this case report, we present an occurrence of spinal infection caused by B. melitensis in a 67-year-old man residing in a non-endemic area of southern China. The patient initially presented with chest and back pain, which was not accurately diagnosed and treated at a local hospital. Subsequently, due to worsening pain, he was admitted to our hospital. To determine the cause of the infection, we performed CT-guided aspiration biopsy and collected biopsy tissue for metagenomic next-generation sequencing (mNGS) on the second day of hospitalization. Imaging investigations revealed involvement of the thoracic vertebrae, specifically thoracic 4– 7 with the main focus on 5– 6, accompanied by stenosis of the intervertebral space. The mNGS results indicated that the spine infection was caused by B. melitensis. The patient’s history as a shepherd and a positive Rose Bengal plate test (RBPT) further supported the diagnosis of brucella spondylitis. In order to alleviate pain and restore spinal function, the patient underwent posterior internal fixation of the thoracic spine. Treatment was initiated with cefoperazone/sulbactam, followed by doxycycline. Subsequently, the patient was switched to a combination therapy of rifampicin and doxycycline for a duration of six weeks. The patient responded well to treatment, and his condition remained stable. In conclusion, brucellosis is a common disease that can be easily misdiagnosed. This case report highlights the potential value of mNGS in early and rapid diagnosis. We believe that mNGS can serve as an effective tool to improve the diagnosis of spine infections caused by this pathogen.Keywords: spine infection, Brucella melitensis, metagenomic next-generation sequencing, Rose Bengal plate test

Xuan Wan,1,&ast; Yuting Fang,2,&ast; Jiangzhou Du,1 Shaoxi Cai,1 Hangming Dong1 1Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, People’s Republic of China; 2BSL-3 Laboratory, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaoxi Cai; Hangming Dong, Email hxkc@smu.edu.cn; dhm@smu.edu.cnObjective: GW4869 is an exosomal inhibitor. It is necessary to delay the occurrence of gefitinib resistance during non-small-cell lung cancer (NSCLC) treatment. This study aimed to investigate the anti-tumor effects of GW4869 on epithelial-mesenchymal transition (EMT) and expression of extracellular heat shock protein 90α (eHSP90α) that contributes to acquired resisitance. Our study provides a new sight into the treatment of EGFR-mutated NSCLC.Materials and Methods: We performed western blotting to detect levels of EMT and eHSP90α. Wound healing and transwell assays were performed to evaluate the behavioral dynamics of EMT. A nude mouse model of HCC827 was established in vivo.Results: GW4869 inhibited the expression of eHSP90α, EMT, invasion and migration abilities of HCC827 and PC9. GW4869 enhanced sensitivity to gefitinib in BALB/c nude mice bearing tumors of HCC827.Conclusion: These studies suggest that GW4869 can inhibit EMT and extracellular HSP90α, providing new strategies for enhancing gefitinib sensitivity in NSCLC.Keywords: GW4869, EMT, gefitinib-sensitive NSCLC, eHSP90&#x03B1

Jing Du, Xin Zhao, Xiumei Xu, Zhichao Zhang, Xiaomei Zhang Department of Endocrinology and Metabolism, Peking University International Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xiaomei Zhang, Department of Endocrinology and metabolism, Peking University International Hospital, No. 1 Life Garden Road Zhongguancun Life Science Garden Changping District, Beijing, People’s Republic of China, Tel/Fax +86-010-69006105, Email z.x.mei@163.comPurpose: To explore the association between thyroid parameters and subclinical atherosclerosis (AS) in hospitalised euthyroid patients with type 2 diabetes mellitus (T2DM).Patients and Methods: A retrospective analysis was conducted involving 1245 inpatients with T2DM. Free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) levels were measured, and carotid artery ultrasonography was performed. Thyroid hormone (TH) sensitivity was evaluated using thyroid feedback quantile-based index (TFQI), TSH index (TSHI), thyrotropin thyroxine resistance index (TT4RI), and free triiodothyronine/free thyroxine ratio (FT3/FT4).Results: In inpatients with T2DM having normal thyroid function, the incidence of subclinical AS declined with increasing levels of FT3, FT4, and FT3/FT4 (P trend < 0.05). Logistic regression analysis revealed that FT4 (OR, 0.914; 95% CI, 0.845– 0.989), FT3 (OR, 0.374; 95% CI, 0.277– 0.504), and FT3/FT4 (OR, 0.036; 95% CI, 0.013– 0.061) were independently associated with subclinical AS (P < 0.05). However, TSH, TFQI, TSHI, and TT4RI levels were not associated with subclinical AS (P > 0.05). FT3/FT4 demonstrated superior predictive accuracy for subclinical AS than that of FT3 or FT4 alone (P < 0.001), with a cutoff point of 0.25.Conclusion: In euthyroid inpatients with T2DM, subclinical AS exhibited negative correlation with FT3, FT4, and FT3/FT4 levels, independent of other risk factors for AS. Additionally, FT3/FT4 ratio had a good predictive value for subclinical AS.Keywords: thyroid hormone, thyroid hormone sensitivity, euthyroid, diabetes mellitus, atherosclerosis

Canbin Dong,1,&ast; Fang Liu,1,&ast; Zuda Liao,2 Lanmei Lin,1 Runnan Wang,1 Juan Du,1 Wen Huang1 1Department of Dermatology, Huashan Hospital, Fudan University, Shanghai Institute of Dermatology, Shanghai, People’s Republic of China; 2Medical Insurance Office of Huashan Hospital Affiliated, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan Du; Wen Huang, Department of Dermatology, Huashan Hospital, Fudan University, Shanghai Institute of Dermatology, Shanghai, 200040, People’s Republic of China, Tel +86-21-52889999, Fax +86-21-52887782, Email dujuan@huashan.org.cn; huangwen2@huashan.org.cnBackground: There are still some gaps in the summary and generalization of cosmetic-related adverse reaction reports.Objective: The aim of this study is to summarize and analyze the occurrence of cosmetic adverse reactions in Shanghai Han population by using available survey data.Materials and Methods: Collection, statistics and analysis of patients with cosmetic adverse reactions in Shanghai Huashan Hospital from 2017 to 2021.Results: Among the 1004 patients, most of them (96.71%) were diagnosed as cosmetic contact dermatitis, which often occurred within 3 days of using cosmetics (51.79%). A total of 260 patients were tested with patch test, but the compliance rate was only 18.08%. Among them, 240 patients underwent additional European standard allergen tests, and positive allergens were detected in 210 cases (87.5%). Univariate analysis revealed that dosage form (emulsion and cream), age (≤ 25 years) and the allergic ingredients triethanolamine, rose oil, propylene glycol, thiomersal and musk ambrette are associated with the occurrence of cosmetic adverse reactions within seven days. A logit prediction model was also successfully constructed: Logit (P) = 1.710– 0.796× 1 + 1.185× 2 − 3.650X3-1.335X4.Conclusion: This study complements the data reported on cosmetic adverse reactions in the Chinese Han population and suggests that in future clinical diagnosis and data collection, emphasis should be placed on patch testing, combining the patch test with cosmetic protoplast with the European standard allergen test to improve the detection rate.Keywords: adverse reaction reporting, cosmetics, contact dermatitis, personal care products, patch tests

The consecutive occurrence of three large wildfires in 1 year is rarely seen in northern California including the deadliest case during 8–25 November 2018 in Butte County. They happened under favorable fuel and meteorological conditions including long-term warming trends, normal summer-autumn warm-dry climate, and extreme heated air masses with strong offshore wind. The former two meteorological conditions contribute a background for large wildfires but extreme heated air masses and strong offshore winds are critical potentials for a fire spread. The relationship between extreme heated/cooled air masses and the three large wildfires was carefully examined from their starts to extinguishing. An anomaly-based synoptic analysis method is used by separating atmospheric variables into climatology and anomalies. A 3-dimensional anomalous synoptic pattern of atmospheric variables is established for the three wildfire cases in 2018. The analysis showed that one anomalous warm-air mass in the mid-to-low troposphere dynamically associated with a positive center of geopotential height (GPH) anomalies at the upper troposphere (150–300 hPa) is an anomalous synoptic pattern indicating a potential large wildfire spread, and conversely by negative anomalies when the fires were extinguished. The ECMWF model seems to be capable of predicting such anomalous temperature-pressure patterns to indicate possible fire spread and extinguishing.

Xiaoyu Pan,1,&ast; Huazheng Zhu,2,&ast; Jinglong Du,1 Guangtao Hu,1 Baoru Han,1 Yuanyuan Jia1 1College of Medical Informatics, Chongqing Medical University, Chongqing, People’s Republic of China; 2College of Intelligent Technology and Engineering, Chongqing University of Science and Technology, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanyuan Jia, Email yyjia@cqu.edu.cnAim: The Coronavirus Disease 2019 (COVID-19) pandemic has increased the public health burden and brought profound disaster to humans. For the particularity of the COVID-19 medical images with blurred boundaries, low contrast and different infection sites, some researchers have improved the accuracy by adding more complexity. Also, they overlook the complexity of lesions, which hinder their ability to capture the relationship between segmentation sites and the background, as well as the edge contours and global context. However, increasing the computational complexity, parameters and inference speed is unfavorable for model transfer from laboratory to clinic. A perfect segmentation network needs to balance the above three factors completely. To solve the above issues, this paper propose a symmetric automatic segmentation framework named MS-DCANet. We introduce Tokenized MLP block, a novel attention scheme that uses a shift-window mechanism to conditionally fuse local and global features to get more continuous boundaries and spatial positioning capabilities. It has greater understanding of irregular lesion contours. MS-DCANet also uses several Dual Channel blocks and a Res-ASPP block to improve the ability to recognize small targets. On multi-modality COVID-19 tasks, MS-DCANet achieved state-of-the-art performance compared with other baselines. It can well trade off the accuracy and complexity. To prove the strong generalization ability of our proposed model, we apply it to other tasks (ISIC 2018 and BAA) and achieve satisfactory results.Patients: The X-ray dataset from Qatar University which contains 3379 cases for light, normal and heavy COVID-19 lung infection. The CT dataset contains the scans of 10 patient cases with COVID-19, a total of 1562 CT axial slices. The BAA dataset is obtained from the hospital and includes 387 original images. The ISIC 2018 dataset is from the International Skin Imaging Collaborative (ISIC) containing 2594 original images.Results: The proposed MS-DCANet achieved evaluation metrics (MIOU) of 73.86, 97.26, 89.54, and 79.54 on the four datasets, respectively, far exceeding other current state-of-the art baselines.Conclusion: The proposed MS-DCANet can help clinicians to automate the diagnosis of COVID-19 patients with different symptoms.Keywords: multi-modality COVID-19 lesion segmentations, laboratory to clinic, multi-scale feature learning, depthwise separable convolution

Ran Li,1,2,&ast; Chen Liu,1,2,&ast; Chaoqiong Wan,1,2 Tiantian Liu,1,2 Rongrong Zhang,1,2 Jie Du,1 Xiangyu Wang,1,2 Xiaofeng Jiao,1,2 Ruifang Gao,1,2 Bing Li1 1Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, People’s Republic of China; 2Department of Pediatric and Preventive Dentistry, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruifang Gao; Bing Li, Email gruifang_26@163.com; libing-1975@163.comPurpose: Oral squamous cell carcinoma (OSCC) is a malignant disease with serious impacts on human health and quality of life worldwide. This disease is traditionally treated through a combination of surgery, radiotherapy, and chemotherapy. However, the efficacy of traditional treatments is hindered by systemic toxicity, limited therapeutic effects, and drug resistance. Fibroblast activation protein (FAP) is a membrane-bound protease. Although FAP has limited expression in normal adult tissues, it is highly expressed in the tumor microenvironment of many solid cancers – a characteristic that makes it an ideal target for anticancer therapy. In this study, we constructed a nano-drug delivery system (NPF@DOX) targeting FAP to increase the therapeutic efficiency of synergistic chemo-photothermal therapy against OSCC.Methods: We utilized PEGylated nano-graphene oxide (NGO) to link doxorubicin (DOX) and fluorescently-labeled, FAP-targeted peptide chains via hydrogen bonding and π–π bonding to enhance the targeting capability of NPF@DOX. The synthesis of NPF@DOX was analyzed using UV–Vis and FT–IR spectroscopy and its morphology using transmission electron microscopy (TEM). Additionally, the drug uptake efficiency in vitro, photo-thermal properties, release performance, and anti-tumor effects of NPF@DOX were evaluated and further demonstrated in vivo.Results: Data derived from FT–IR, UV–Vis, and TEM implied successful construction of the NPF@DOX nano-drug delivery system. Confocal laser scanning microscopy images and in vivo experiments demonstrated the targeting effects of FAP on OSCC. Furthermore, NPF@DOX exhibited a high photothermal conversion efficiency (52.48%) under near-infrared radiation. The thermogenic effect of NPF@DOX simultaneously promoted local release of DOX and apoptosis based on a pH-stimulated effect. Importantly, FAP-targeted NPF@DOX in combination with PTT showed better tumor suppression performance in vivo and in vitro than did either therapy individually.Conclusion: NPF@DOX can precisely target OSCC, and combined treatment with chemical and photothermal therapy can improve the therapeutic outcomes of OSCC. This method serves as an efficient therapeutic strategy for the development of synergistic anti-tumor research.Keywords: fibroblast activation protein, nano-graphene oxide, photothermal therapy, oral squamous cell carcinoma, targeted combination therapy

Jingya Duan,1,&ast; Zisen Zhang,2,&ast; Jinfeng Du,2 Jihua Zhang,1 Minmin Li,1 Canyu Li1 1Department of Gynecology, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China; 2Department of Oncology, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Canyu Li, Department of Gynecology, the Third Affiliated Hospital of Zhengzhou University, No. 7, Kangfuzhong Street, Erqi District, Zhengzhou City, Henan Province, 450052, People’s Republic of China, Tel/Fax +86-0371-66903480, Email lcy200507@zzu.edu.cnPurpose: Ovarian cancer is the most lethal malignancy in gynecology. Due to limited treatment strategies and platinum resistance, newer drugs and therapeutic options are needed. Esomeprazole (ESO) has been reported to have multiple anticancer activities in preclinical and clinical research. Therefore, this study aimed to explore the anticancer effects of esomeprazole on ovarian cancer and its underlying molecular mechanisms.Methods: CCK-8 and 5-ethynyl-2′-deoxyuridine (EdU) assays were used to detect cell viability and proliferation. The Transwell assay was used to evaluate cell migration and invasion capacity. Flow cytometry was used to detect cell apoptosis. Western blotting and immunofluorescence were used to detect protein expression.Results: ESO effectively inhibited the cell viability, proliferation, invasion, migration, and induced apoptosis of ovarian cancer cells in a concentration-dependent manner. Treatment with ESO decreased the expression of c-MYC, SKP2, E2F1, N-cadherin, vimentin, and matrix metalloproteinase 2 (MMP2), while it increased E-cadherin, caspase3, p53, BAX, and cleaved poly (ADP-ribose) polymerase (PARP) expression, and downregulated the PI3K/AKT/mTOR signaling pathway. Furthermore, ESO combined with cisplatin showed synergistic effects in inhibiting proliferation, invasion, and migration of cisplatin-resistant ovarian cancer cells. The mechanism may be related to the increased inhibition of c-MYC, epithelial-mesenchymal transition (EMT), and the AKT/mTOR signaling pathway and enhanced the upregulation of the pro-apoptotic protein BAX and cleaved PARP levels. Moreover, ESO combined with cisplatin synergistically upregulated the expression of the DNA damage marker γH2A.X.Conclusion: ESO exerts multiple anticancer activities and has a synergistic effect in combination with cisplatin on cisplatin-resistant ovarian cancer cells. This study provides a promising strategy to improve chemosensitivity and overcome resistance to cisplatin in ovarian cancer.Keywords: esomeprazole, ovarian cancer, cisplatin resistance, synergistic effect, AKT/mTOR pathway

ObjectiveMeniscal degeneration is strongly associated with osteoarthritis (OA). We aimed to evaluate a 3D ultrashort-echo-time Cones magnetization transfer (UTE-Cones-MT) sequence for quantification of macromolecular fraction (MMF) and MT ratio (MTR) in menisci of healthy volunteers and patients with different degrees of OA.MethodsPatients with mild OA (n = 19; 37-86 years; 10 males) or advanced OA (n = 12; 52-88 years; 4 males) and healthy volunteers (n = 17; 20-49 years; 7 males) were scanned with T2-FSE and UTE-Cones-MT sequences at 3T. Morphological assessment was performed using meniscal whole-organ magnetic resonance imaging score (WORMS). MMF and MTR were calculated for menisci, and correlated with age and meniscal WORMS scores. The diagnostic efficiency was performed by using receiver operating characteristic (ROC) curve and the area under the curve (AUC) analyses.ResultsDecreased MMF and MTR were observed in menisci of patients with mild or advanced OA compared with healthy subjects, and in menisci with tears (Grade 2-4) compared with normal menisci (Grade 0). Significant negative correlations were observed between MMF (r = -0.769, P

The quantitative accuracy and precision of brain positron emission tomography (PET) studies can be considerably improved using dedicated brain PET scanners with a uniform high resolution and a high sensitivity across the brain volume. One approach to building such a system is to construct the PET scanner using depth-of-interaction (DOI) encoding detectors with finely segmented and thick crystal arrays. In this paper, the performance of a DOI PET detector based on two 16 × 16 arrays of 2 × 2 mm2 SiPMs coupled to both ends of a 44 × 44 array of 0.69 × 0.69 × 30 mm3 polished LYSO crystals was evaluated at different temperatures (-9°C, 0°C, 10°C, and 20°C) for brain PET applications. The pitch size of the LYSO array is 0.75 mm. The flood histograms show that all the crystal elements in the LYSO array can be resolved except some edge crystals, due to the limited light sharing. The average energy resolution, average DOI resolution, and average timing resolution across crystal elements are 21.1 ± 3.0%, 3.47 ± 0.17 mm, and 1.38 ± 0.09 ns, respectively, which were obtained at a bias voltage of 56.5 V and a temperature of 0°C.

Background and purposeMR imaging has been widely used for the noninvasive evaluation of MS. Although clinical MR imaging sequences are highly effective in showing focal macroscopic tissue abnormalities in the brains of patients with MS, they are not specific to myelin and correlate poorly with disability. We investigated direct imaging of myelin using a 2D adiabatic inversion recovery ultrashort TE sequence to determine its value in assessing disability in MS.Materials and methodsThe 2D inversion recovery ultrashort TE sequence was evaluated in 14 healthy volunteers and 31 patients with MS. MPRAGE and T2-FLAIR images were acquired for comparison. Advanced Normalization Tools were used to correlate inversion recovery ultrashort TE, MPRAGE, and T2-FLAIR images with disability assessed by the Expanded Disability Status Scale.ResultsWeak correlations were observed between normal-appearing white matter volume (R = -0.03, P = .88), lesion load (R = 0.22, P = .24), and age (R = 0.14, P = .44), and disability. The MPRAGE signal in normal-appearing white matter showed a weak correlation with age (R = -0.10, P = .49) and disability (R = -0.19, P = .31). The T2-FLAIR signal in normal-appearing white matter showed a weak correlation with age (R = 0.01, P = .93) and disability (R = 0.13, P = .49). The inversion recovery ultrashort TE signal was significantly negatively correlated with age (R = -0.38, P = .009) and disability (R = -0.44; P = .01).ConclusionsDirect imaging of myelin correlates with disability in patients with MS better than indirect imaging of long-T2 water in WM using conventional clinical sequences.

Xinxin Li, Yifang Sun, Juan Du, Fang Wang, Xiaolan Ding Department of Dermatology, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xiaolan Ding, Department of Dermatology, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China, Tel +8613522658992, Fax +861088325474, Email Lancyding@126.comAbstract: Vitiligo is an acquired autoimmune skin disorder, clinically characterized by distinct white macules and patches resulting from progressive melanocyte destruction. JAK-STAT pathway plays an important role in the loss of epidermal melanocytes. Baricitinib can block the JAK-STAT pathway and the downstream chemokines as a new JAK1/2 inhibitor. In this report, we describe the successful treatment of 2 patients with oral baricitinib combined with NB-UVB phototherapy, which provides a good alternative and supplementary to treat refractory vitiligo.Keywords: IFN-γ signaling pathway, Janus kinase inhibitor, baricitinib, vitiligo

As China’s natural resource governance has turned to high-quality management, establishing reasonable and ecological land-use patterns is an effective means of promoting natural resource utilization and improving the quality of the ecological environment. Therefore, this study used ecological land as the expansion source to construct an ecological land-use pattern with the minimum cumulative resistance model in Haixing County, China, based on regional food security, ecological security, and construction land expansion patterns. This work also involved designing ecological corridors, radiation channels, strategic nodes, and other ecological components. The results demonstrate that (1) the ecological land source is 7976.93 hm2, accounting for 9.19% of the total area. It is mainly distributed in the southeast of the county, mainly in the river system and woodland; (2) the food security situation of Haixing County can be divided into four zones, most of which are agricultural adjustment areas, indicating that the ecological security of cultivated land in this area needs to be improved; (3) the ecological security level of Haixing County is divided into four areas, and the ideal safety zone accounts for the smallest area, indicating that the regional ecological situation is very unstable; (4) construction land expansion zone is divided into four parts. A suitable construction zone occupies the largest area and is mainly distributed around the current construction land; (5) the expansion of the ecological land-use pattern of Haixing County includes four zones, 15 ecological corridors, 12 radiation channels, and 35 strategic nodes, which is conducive to optimal land allocation from an ecological security perspective. This paper puts forward some suggestions for ecological protection and intensive urban development.