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Zhaoting Wu,1,2 Lihua Tang,1 Yaozhen Lai,1 Muyuan Liu,3 Li Zhou1 1Department of Gynecologic Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 2Department of Gynecology, the First People’s Hospital of Chenzhou, Chenzhou, Hunan, People’s Republic of China; 3Head and Neck Surgery Department, Cancer Hospital of Shantou University, Medical College, Shantou, Guangdong, People’s Republic of ChinaCorrespondence: Li Zhou, Email zlyyzl@126.com Muyuan Liu, Email muyuan-1981@163.comPurpose: Struma ovarii is a highly specialized teratoma consisting primarily of mature thyroid tissue. However, malignant struma ovarii coexisting with thyroid carcinoma, not to mention autoimmune disease, is uncommon. Malignant struma ovarii complicated with papillary thyroid carcinoma, Hashimoto’s thyroiditis and polycystic ovarian syndrome has never been reported in literature.Patients and Methods: A 32-year-old female was admitted to our hospital due to a history of abdominal distension and menolipsis over the past half a year. Physical examination touched a 6 × 6 cm mass with a clear boundary, normal movement, and no pressing pain in the right adnexal area, Imaging revealed a cystic solid mass of 6 × 7 cm in the right ovary and the level of tumor markers including CA125, CA199, CA153, CEA, AFP were normal, but with low TSH and increased TPOAb, TGAb, TRAb. Laparoscopic right ovary tumor resection was performed, followed by comprehensive staging surgery, as well as thyroidectomy after pathologic diagnosis. The patient was diagnosed with a combination of follicular thyroid cancer from struma ovarii, papillary thyroid carcinoma and Hashimoto’s thyroiditis, along with polycystic ovarian syndrome. Immunohistochemical staining showed positivity for Ag, CK-pan, CK7, PAX8 and TTF-1 in the right ovarian mass, and the left thyroid was positive for the BRAF V600E mutation.Results: The patient underwent thyroxine suppression therapy and radioactive iodine 131I therapy after operation. Serum thyroglobulin was undetectable, and no signs of recurrence or metastasis were detected in the imaging examination at the 2-year follow-up.Conclusion: Malignant struma ovarii coexisting with thyroid carcinoma is rare. No report has been identified in literature review on the rare malignant struma ovarii coexisting with thyroid carcinoma, Hashimoto’s thyroiditis and polycystic ovarian syndrome. Our case can offer experience of diagnosis and treatment to some extent for such rare case. Therefore, it is essential to consider the association between ovarian tumors and the endocrine system. This case is valuable in understanding the diagnosis and management of such an unusual complicated disease.Keywords: struma ovarii, follicular thyroid carcinoma, case report, gynaecological tumor

Yi Tang,1,&ast; Zemin Wei,1,&ast; Ning Li,2 Chao Jiang,2 Chen Liang,1 Lulu Sun,2 Lufeng Tian,3 Zhengyu Jin,4 Zhe Wu,2,&ast; Hao Sun4,&ast; 1Department of Endocrinology, Fushun Central Hospital, Fushun, Liaoning Province, People’s Republic of China; 2Department of Radiology, Fushun Central Hospital, Fushun, Liaoning Province, People’s Republic of China; 3Department of Internal Medicine, Fushun Central Hospital, Fushun, Liaoning Province, People’s Republic of China; 4Department of Radiology, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Sun, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86-10-69159537, Email sunhao_robert@126.com Zhe Wu, Fushun Central Hospital, Xincheng Road, Shuncheng District, Fushun, Liaoning Province, 113006, People’s Republic of China, Tel +86-156-42018778, Email wuzhe0306@163.comPurpose: To examine the risk of type 2 diabetes mellitus in non-obese patients with pancreatic fatty infiltration through abdominal computed tomography (CT) quantitation.Patients and Methods: We carried out a retrospective analysis of abdominal CT and inpatient medical records of 238 inpatients from July 2019 to April 2021. The patients were divided into a normal non-obese group (BMI < 25, n = 135) and diabetic non-obese group (BMI < 25, n = 103). Abdominal CT-related parameters included body width; mean CT values of the pancreas, liver, and spleen; difference between pancreas and spleen CT values (P−S); pancreas-to-spleen attenuation ratio (P/S); and liver-to-spleen attenuation ratio (L/S). Logistic regression was used to estimate the risk factors for comorbid diabetes in a non-obese population.Results: The P-values of the pancreas CT value, P−S, P/S, body width, and L/S were all < 0.05 and correlated to comorbid diabetes in non-obese patients. Worsening pancreatic fatty infiltration increased the risk of developing diabetes. Using a P/S of 1.0 as reference, every successive decrease in this ratio by 0.1 increases patient risk by 3.981, 4.452, 6.037, and 12.937 times.Conclusion: The risk of developing type 2 diabetes mellitus in non-obese patients increases with the degree of pancreatic fatty infiltration as assessed by CT.Keywords: computed tomography, non-obese patients, pancreatic fatty infiltration, type 2 diabetes mellitus

Xiaojuan Ji,1,&ast; Wenjie Zhu,1,&ast; Hongfei Lu,2 Zhiwei Wu,1 Huaqing Chen,1 Chunli Lin,1 Zhaolin Zeng,1 Cong You,1 Longnian Li1 1Department of Dermatology, First Affiliated Hospital of Gannan Medical University, Joint Organization of Jiangxi Clinical Medicine Research Center for Dermatology, Ganzhou, People’s Republic of China; 2Clinical Laboratory, First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cong You; Longnian Li, Department of Dermatology, First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China, Email youcong1987@tmu.edu.cn; li_longnian@foxmail.comObjective: To analyze the antibiotic resistance profile, virulence genes, and molecular typing of Staphylococcus aureus (S. aureus) strains isolated in skin and soft tissue infections at the First Affiliated Hospital, Gannan Medical University, to better understand the molecular epidemiological characteristics of S. aureus.Methods: In 2023, 65 S. aureus strains were isolated from patients with skin and soft tissue infections. Strain identification and susceptibility tests were performed using VITEK 2 and gram-positive bacteria identification cards. DNA was extracted using a DNA extraction kit, and all genes were amplified using polymerase chain reaction. Multilocus sequence typing (MLST) was used for molecular typing.Results: In this study, of the 65 S. aureus strains were tested for their susceptibility to 16 antibiotics, the highest resistance rate to penicillin G was 95.4%. None of the staphylococcal isolates showed resistance to ceftaroline, daptomycin, linezolid, tigecycline, teicoplanin, or vancomycin. fnbA was the most prevalent virulence gene (100%) in S. aureus strains isolated in skin and soft tissue infections, followed by arcA (98.5%). Statistical analyses showed that the resistance rates of methicillin-resistant S. aureus isolates to various antibiotics were significantly higher than those of methicillin-susceptible S. aureus isolates. Fifty sequence types (STs), including 44 new ones, were identified by MLST.Conclusion: In this study, the high resistance rate to penicillin G and the high carrying rate of virulence gene fnbA and arcA of S.aureus were determine, and 44 new STs were identified, which may be associated with the geographical location of southern Jiangxi and local trends in antibiotic use. The study of the clonal lineage and evolutionary relationships of S. aureus in these regions may help in understanding the molecular epidemiology and provide the experimental basis for pathogenic bacteria prevention and treatment.Keywords: Staphylococcus aureus, skin and soft tissue infections, antibiotic resistance, multilocus sequence typing, virulence gene

Nan Geng,1,&ast; Zhipeng Wu,2– 4,&ast; Zhao Liu,1 Wen Pan,1 Yueke Zhu,1 Hongbo Shi,3 Ying Han,5 Yingmin Ma,2– 4 Bo Liu1 1Department of Emergency Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 3Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 4Beijing Research Center for Respiratory Infectious Diseases, Beijing, 100013, People’s Republic of China; 5Department of Gastroenterology and Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingmin Ma, Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, No. 8, Xi Tou Tiao, Youanmenwai Street, Fengtai District, Beijing City, 100069, People’s Republic of China, Email ma.yingmin@163.com Bo Liu, Department of Emergency Medicine, Beijing Youan Hospital, Capital Medical University, No. 8, Xi Tou Tiao, Youanmenwai Street, Fengtai District, Beijing City, 100069, People’s Republic of China, Email Rippleyayy@sina.comBackground: Research on biomarkers associated with the severity and adverse prognosis of COVID-19 can be beneficial for improving patient outcomes. However, there is limited research on the role of soluble TREM-1 (sTREM-1) in predicting the severity and prognosis of COVID-19 patients.Methods: A total of 115 COVID-19 patients admitted to the emergency department of Beijing Youan Hospital from February to May 2023 were included in the study. Demographic information, laboratory measurements, and blood samples for sTREM-1 levels were collected upon admission.Results: Our study found that sTREM-1 levels in the plasma of COVID-19 patients increased with the severity of the disease (moderate vs mild, p=0.0013; severe vs moderate, p=0.0195). sTREM-1 had good predictive value for disease severity and 28-day mortality (area under the ROC curve was 0.762 and 0.805, respectively). sTREM-1 also exhibited significant correlations with age, body temperature, respiratory rate, PaO2/FiO2, PCT, CRP, and CAR. Ultimately, through multivariate logistic regression analysis, we determined that sTREM-1 (OR 1.008, 95% CI: 1.002– 1.013, p=0.005), HGB (OR 0.966, 95% CI: 0.935– 0.998, p=0.036), D-dimer (OR 1.001, 95% CI: 1.000– 1.001, p=0.009), and CAR (OR 1.761, 95% CI: 1.154– 2.688, p=0.009) were independent predictors of 28-day mortality in COVID-19 patients. The combination of these four markers yielded a strong predictive value for 28-day mortality in COVID-19 cases with an AUC of 0.919 (95% CI: 0.857 − 0.981).Conclusion: sTREM-1 demonstrated good predictive value for disease severity and 28-day mortality, serving as an independent prognostic factor for adverse patient outcomes. In the future, we anticipate conducting large-scale multicenter studies to validate our research findings.Keywords: COVID-19, sTREM-1, inflammation-related markers, disease severity, 28-day mortality

Ziting Wu,1– 3 Jiangxia Yu,4 Beini Lyu,2 Haoxiang Lin,2 Shanshan Li,5,6 Gordon G Liu1– 3 1National School of Development, Peking University, Beijing, 100871, People’s Republic of China; 2Institute for Global Health and Development, Peking University, Beijing, 100871, People’s Republic of China; 3PKU China Center for Health Economic Research, Peking University, Beijing, 100871, People’s Republic of China; 4School of Medicine and Health Management, Guizhou Medical University, Guiyang, 550025, People’s Republic of China; 5Center for International Cooperation and Disciplinary Innovation of Income Distribution and Public Finance (111 Center), Zhongnan University of Economics and Law, Wuhan, 430073, People’s Republic of China; 6Hubei Finance and Development Research Center, Zhongnan University of Economics and Law, Wuhan, 430073, People’s Republic of ChinaCorrespondence: Shanshan Li, Center for International Cooperation and Disciplinary Innovation of Income Distribution and Public Finance (111 Center), Zhongnan University of Economics and Law, Wuhan, 430073, People’s Republic of China, Email lishanceee@163.com Gordon G Liu, National School of Development, Peking University, Beijing, 100871, People’s Republic of China, Email gordonliu@nsd.pku.edu.cnObjective: Culture and eating habits, which vary greatly across different ethnic groups, have a substantial impact on drinking behavior. This study aimed to examine whether the drinking patterns and reasons differ by ethnic groups, and provide useful insights for multi-ethnic areas that seek to cut down alcohol intake.Methods: We recruited excessive drinkers and collected the drinking patterns and motivations by questionnaire in a multi-ethnic society. Multiple linear regressions were used to evaluate the variations in drinking characteristics among different ethnic groups.Results: We recruited 1287 participants through convenience sampling (a non-probability sampling technique used in research where the researcher selects participants or units for a study based on their accessibility and proximity), among whom 439 excessive drinkers were eligible. The mean age was 38 years for the 439 participants, 92.9% were men, 36.0% were Han, and 64.0% were minorities mainly composed of the Yi. The majority of the participants were married (75.9%) and did physical work (58.1%). Ethnic minorities consumed more alcohol on a single occasion than Han people did (47.3 vs 41.8g/session) while drinking less frequently. For the minority and Han participants, 67% and 42% were not used to drinking with food, respectively. Peer pressure and fostering a good atmosphere were the most common drinking reasons for the minority and Han, respectively.Conclusion: We found substantial differences in drinking patterns and reasons between ethnic minorities and Han ethnicity, attributable to their culture and customs. Findings highlight the importance of drinking habits and motivations in exploring alcohol control education strategies in the context of ethnic integration and population immigration.Keywords: health education, alcohol drinking habits, motivations, ethnic groups

Jingyi Lao,1,&ast; Yijie Zeng,1,&ast; Zhangying Wu,1 Gaohong Lin,1 Qiang Wang,1 Mingfeng Yang,1 Si Zhang,1 Danyan Xu,1 Min Zhang,1 Kexin Yao,1 Shuang Liang,1 Qin Liu,1 Jiafu Li,1 Xiaomei Zhong,1 Yuping Ning1– 4 1Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2The First School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 3Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, People’s Republic of China; 4Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuping Ning; Xiaomei Zhong, The Affiliated Brain Hospital of Guangzhou Medical University, No. 36, Mingxin Road, Liwan District, Guangzhou, Guangdong, People’s Republic of China, Email ningjeny@126.com; lovlaugh@163.comBackground: Late-life depression (LLD) is characterized by disrupted brain networks. Resting-state networks in the brain are composed of both stable and transient topological structures known as microstates, which reflect the dynamics of the neural activities. However, the specific pattern of EEG microstate in LLD remains unclear.Methods: Resting-state EEG were recorded for 31 patients with episodic LLD (eLLD), 20 patients with remitted LLD (rLLD) and 32 healthy controls (HCs) using a 64-channel cap. The clinical data of the patients were collected and the 17-Item Hamilton Rating Scale for Depression (HAMD) was used for symptom assessment. Duration, occurrence, time coverage and syntax of the four microstate classes (A-D) were calculated. Group differences in EEG microstates and the relationship between microstates parameters and clinical features were analyzed.Results: Compared with NC and patients with rLLD, patients with eLLD showed increased duration and time coverage of microstate class D. Besides, a decrease in occurrence of microstate C and transition probability between microstate B and C was observed. In addition, the time coverage of microstate D was positively correlated with the total score of HAMD, core symptoms, and miscellaneous items.Conclusion: These findings suggest that disrupted EEG microstates may be associated with the pathophysiology of LLD and may serve as potential state markers for the monitoring of the disease.Keywords: late-life depression, microstate, electroencephalogram, resting-state networks

Zhiwei Wu, Changhao Huang Department of Organ Transplantation, XiangYa Hospital of Central South University, Changsha, People’s Republic of ChinaCorrespondence: Changhao Huang, Email Chhuang@csu.edu.cnPurpose: Mannose receptor C-type 1 (MRC1) is an endocytic lectin receptor primarily expressed in macrophages, dendritic cells, and some endothelial cells. However, the role of MRC1 in cancers remains unclear.Methods: We analyzed MRC1 expression using The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), and single-cell datasets. We systematically explored the prognostic implications and diagnostic value of MRC1. Immune-related indicators, including immune cells, immune scores, and immune checkpoint molecules, were used to estimate their correlation with MRC1 expression. Finally, we explored its potential ties to immunotherapy success markers such as tumor mutation burden and DNA repair genes.Results: MRC1 showed both pro- and anti-tumor leanings depending on the cancer types. High levels correlated with poorer outcomes in six cancers but improved prognosis in some cancers like glioblastoma multiforme. This trend extended to the immune arena, where MRC1 intertwined with diverse immune parameters, suggesting its influence on affecting the tumor’s immunological landscape. Intriguingly, its expression positively associated with factors favoring immunotherapy efficacy while negatively correlating with some potential barriers. Single-cell analysis pinpointed a specific link between MRC1 and DNA damage/repair pathways in breast cancer.Conclusion: Our study provides a comprehensive landscape of MRC1 levels and diverse regulatory patterns in different cancers, deepening the understanding of MRC1’s roles in tumorigenesis and immunity.Keywords: MRC1, biomarker, immunotherapy, single-cell, pan-cancer analysis

Han Luo,1,&ast; Xiaofei Wang,1,&ast; Mengqi Fang,1 Huifan Yu,1 Lili Gui,1 Zhengkun Wu,1 Jianyong Sheng,2 Fei Li1 1Hubei Key Laboratory of Wudang Local Chinese Medicine Research, School of Pharmaceutical Sciences, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 2Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Li, Hubei University of Medicine, 30 Renmin South Road, Shiyan, Hubei, 442000, People’s Republic of China, Email piaopodexinlifei@163.comIntroduction: Although flavonoid compounds exhibit various pharmacological activities, their clinical applications are restricted by low oral bioavailability owing to their poor solubility. Nanocrystals (NCs) represent an excellent strategy for enhancing the oral bioavailability of flavonoids. Hydroxyethyl starch (HES), a biomaterial compound used as a plasma expander, could be an ideal stabilizer material for preparing flavonoid NCs.Methods: HES was used to stabilize flavonoid nanocrystals (NCs), using luteolin (LUT) as a model drug. After full characterization, the freeze-drying and storage stability, solubility, intestinal absorption, pharmacokinetics, and in vivo anti-hyperuricemic effect of the optimized HES-stabilized LUT NCs (LUT-HES NCs) were investigated.Results: Uniformed LUT-HES NCs were prepared with mean particle size of 191.1± 16.8 nm, zeta potential of about − 23 mV, drug encapsulation efficiency of 98.52 ± 1.01%, and drug loading of 49.26 ± 0.50%. The freeze-dried LUT-HES NCs powder showed good re-dispersibility and storage stability for 9 months. Notably, compared with the coarse drug, LUT-HES NCs exhibited improved saturation solubility (7.49 times), increased drug dissolution rate, enhanced Caco-2 cellular uptake (2.78 times) and oral bioavailability (Fr=355.7%). Pharmacodynamic studies showed that LUT-HES NCs remarkably lowered serum uric acid levels by 69.93% and ameliorated renal damage in hyperuricemic mice.Conclusion: HES is a potential stabilizer for poorly soluble flavonoid NCs and provides a promising strategy for the clinical application of these compounds. LUT-HES NCs may be an alternative or complementary strategy for hyperuricemia treatment.Keywords: Hydroxyethyl starch, nanocrystals, stabilizer, luteolin, oral bioavailability, anti-hyperuricemia

Lihua Dai,1,&ast; Zheqian Wu,1,&ast; Liili Yin,1 Longjian Cheng,1 Qiang Zhou,2 Fei Ding1 1Department of Emergency, Shidong Hospital, ShangHai, People’s Republic of China; 2Department of General Surgery, Eighth People’s Hospital, ShangHai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Ding; Qiang Zhou, Email 10119038@qq.com; rabbit1264@163.comBackground: Upon uptake by stressed cells, functional mitochondria can perform their normal functions, ultimately enhancing the survival of host cells. However, despite the promising results of this approach, there is still a lack of understanding of the specific relationship between nerve cells and functional mitochondria.Methods: Functional mitochondria (F-Mito) were isolated from bone marrow-derived mesenchymal stem cells (BMSCs). The ability of microglia cells to internalize F-Mito was evaluated using a middle cerebral artery occlusion (MCAO) model in C57BL/6J mice and an oxygen-glucose deprivation/reoxygenation (OGD/R) cell model. After OGD/R and F-Mito treatment, the temporal dynamics of intracellular reactive oxygen species (ROS) levels were examined.The relationship between ROS levels and F-Mito uptake was assessed at the individual cell level using MitoSOX, Mitotracker, and HIF-1α labeling.Results: Our findings indicate that microglia cells exhibit enhanced mitochondrial uptake compared to astrocytes. Furthermore, internalized F-Mito reduced ROS levels and HIF-1α levels. Importantly, we found that the ROS response in microglia cells following ischemia is a critical regulator of F-Mito internalization, and promoting autophagy in microglia cells might reduce the uptake of ROS and HIF-1α levels.Conclusion: It is verified that F-Mito derived from BMSCs play a protective role in ischemia-reperfusion injury, as their weakening reduces microglial cell activation and alleviates neuroinflammation.Keywords: neuroinflammation, ROS, stem cell, HIF-1α, ischemic stroke

Xiaofei Wang,1,2,&ast; Jihang Dai,2,&ast; Zhimin Wu,1,2 Yuxia Yang,2 Jian Zhang,2 Xiangji Meng,1,2 Wenkang Liu,2 Wenyong Fei,2 Jingcheng Wang2 1The Graduate School, Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 2Department of Orthopedics, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenyong Fei; Jingcheng Wang, Email sbydyx105@126.com; yzwangjingcheng@163.comObjective: To compare the clinical efficacy of artificial total hip arthroplasty(THA) for femoral neck fracture between direct anterior approach(DAA) in lateral position and posterior lateral approach(PLA).Methods: Comparison of 200 cases of patients who underwent THA collected between September 2019 and August 2021 was done. Incision length, intraoperative bleeding, operative time, difference in postoperative haemoglobin from preoperative levels, length of hospital stay, postoperative time to get off the floor, visual analogue score (VAS) for pain, preoperative and postoperative Harris scores for the hip, and measurements of the acetabular abduction angle and anterior acetabular tilt angle at 6 months postoperatively were collected, and all the cases were followed up for at least 2 years.Results: Compared with the PLA group, the DAA group had a shorter incision length, less intraoperative blood loss, less postoperative haemoglobin reduction compared with the preoperative period, a shorter hospital stay and an earlier first time to get off the floor after surgery, however, the comparison of operative times was not statistically significant; Patients in the DAA group had a lower VAS in the early postoperative period compared to PLA; Patients in the DAA group had higher hip Harris scores at 6 weeks and 6 months postoperatively; There was no significant difference in acetabular abduction angle and acetabular anterior tilt angle between the two groups at 6 months postoperatively.Conclusion: Compared to PLA, DAA in THA is minimally invasive, has less pain, less bleeding, earlier time out of bed, shorter hospital stay, better early hip function, faster rehabilitation, and better joint stability.Keywords: direct lateral approach, DAA, femoral neck fractures, total hip arthroplasty, THA, Hip function, postoperative rehabilitation

Hao Wu, Yan Na Shen, Zhongxiao Wu, Feng Mao, You Gang Ren, Li Zhang Department of Dermatology, Ningbo No 6 Hospital, Ningbo, 315040, People’s Republic of ChinaCorrespondence: Li Zhang, Email lishay1022@hotmail.comAbstract: Although the use of biologics has led to great improvement in psoriasis patients, the treatment of psoriasis during pregnancy still faces many challenges. We herein report on a 29-year-old pregnant woman treated with ustekinumab for generalized pustular psoriasis. Upon becoming pregnant, the woman underwent continued treatment with ustekinumab in the first trimester. We also considered the need for neonatal vaccination. The patient discontinued ustekinumab therapy in the second trimester, and during the period of drug discontinuation we noted a slight rash recurrence. The patient was treated with ultraviolet B phototherapy and topical corticosteroids, and the rash was localized to the abdomen. However, in the 27th week of pregnancy, the patient was infected with COVID-19, which made the condition worse. The rash erupted rapidly and spread throughout her body, and she experienced a high fever with her blood count showing augmented numbers of white blood cells. The patients self-administered 0.3 g of acetaminophen three times per day, and after four days her core body temperature was 38.0°C; the rash, however, did not diminish. We diagnosed an outbreak of generalized pustular psoriasis and treated the patient with ustekinumab. The rash resolved quickly, and a healthy newborn was delivered by caesarean section at 39 weeks.Keywords: Ustekinumab, interleukin-12/-23, generalized pustular psoriasis, pregnancy, COVID-19

XiaoLang Miao,1 Yanxia Han,1 Zhenyun Wu,1 Xiaoliang Jin,1 Mei’e Niu,1 Qian Zhao,1 Xiangmin Lu2 1Department of Respiratory Medicine, First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2School of Nursing, Soochow University, Suzhou, People’s Republic of ChinaCorrespondence: Mei’e Niu, Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, 899th, Pinghai Road, Suzhou, 215006, People’s Republic of China, Tel +86 13812671786, Email meniu_123@163.comPurpose: To translate a disease-specific anxiety questionnaire on chronic obstructive pulmonary disease (COPD) and test its reliability and validity in China.Patients and Methods: The German version of the revised COPD Anxiety Questionnaire (CAF-R) was initially validated using step-by-step translation, back-translation, and cross-cultural adaptation. The reliability and validity of the Chinese version of the CAF-R (CAF-R-CN) were tested among 448 patients with COPD (mean age =71.42± 9.33 years, 17.2% female) from four medical institutions in Suzhou, Jiangsu Province, using convenience sampling, from April 2022 to June 2023.Results: The CAF-R-CN included six dimensions with a total of 25 items. The item-level content validity index was 0.860– 1.000; the scale-level content validity index was 0.920. The structural validity χ2/df was 2.326, the root mean square error of approximation was 0.077, the comparative fit index was 0.924, and the Tucker–Lewis index was 0.912. The six-dimensional internal consistency index Cronbach’s α coefficient was 0.696– 0.910, and the test–retest reliability was 0.949. An optimal cut-off score of 50.5 was selected with a sensitivity of 0.786 and specificity of 0.870.Conclusion: The CAF-R-CN had satisfactory reliability and validity and can be used to identify and assess anxiety in COPD patients with a Chinese cultural background.Keywords: fear, scale, specificity, chronic respiratory disease, Chinese translation, assessment

Zhengyi Wu,&ast; Liang Sun,&ast; Yongkang Xu,&ast; He Huang, Zhipeng Wu, Bingbing Qiu, Jinlong Yan, Xiangbao Yin Hepatobiliary Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangbao Yin; Jinlong Yan, Hepatobiliary surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1, Minde Road, Nanchang, Jiangxi Province, People’s Republic of China, Email yxbefy@163.com; yjl19880608@126.comBackground: Chemokines and chemokine receptors (CCRs) are involved in a variety of anti-tumour and pro-tumour immune processes in vivo, such as angiogenesis, metastasis, proliferation and invasiveness, and influence patient prognosis and response to therapy.Methods: CCRs differentially expressed in HCC and associated with prognosis were extracted from TCGA and GEO databases, and the obtained CCRs were then used to construct signature genes, and the signature gene were selected for expression validation as well as functional experiments to explore the role of CCRs in the treatment and prognosis of HCC.Results: We constructed a prognostic model including five CCRs (CCL20, CCL23, CCR3, CCR10, and CXCR3) and validated the expression of signature genes. The model’s risk score is an independent prognostic factor for HCC. We have also developed prognostic model nomograms for clinical use. In addition, we validated that CCR3 expression is associated with poor prognosis in HCC, and the proliferation and migration ability of HCC cells was significantly inhibited after interfering with the expression of CCR3 in MHCC-LM3. We also looked at differences in pathway enrichment, immune infiltration and immune checkpoints. Finally, we found that risk scores were also correlated with drug sensitivity, the high-risk group had a better sensitivity to sorafenib.Conclusion: The CCRs-related gene signature may better assess HCC prognosis and response to immunotherapy and tyrosine kinase inhibitors such as sorafenib in HCC, providing prospective solutions for diagnosis and treatment.Keywords: chemokine, chemokine receptors, prognosis, signature, hepatocellular carcinoma

Wenjie Xie,1,2,&ast; Yixun Zhang,1,2,&ast; Qianfeng Xu,1,2,&ast; Guowei Zhong,1,2 Jundong Lin,2,3 Huichan He,3 Qiuling Du,2 Huijing Tan,1,2 Muqi Chen,1,2 Zhenjie Wu,1– 3 Yulin Deng,1,2 Zhaodong Han,1– 3 Jianming Lu,1,2,4 Jianheng Ye,1,2,4 Fen Zou,1,2 Yangjia Zhuo,1,2 Weide Zhong1– 4 1Department of Urology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China; 2Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China; 3Urology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, People’s Republic of China; 4State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, 999078, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yangjia Zhuo; WeideZhong, Email eyyangjiazhuo@scut.edu.cn; zhongwd2009@live.cnPurpose: Current treatment approaches for Prostate cancer (PCa) often come with debilitating side effects and limited therapeutic outcomes. There is urgent need for an alternative effective and safe treatment for PCa.Methods: We developed a nanoplatform to target prostate cancer cells based on graphdiyne (GDY) and a copper-based metal-organic framework (GDY-CuMOF), that carries the chemotherapy drug doxorubicin (DOX) for cancer treatment. Moreover, to provide GDY-CuMOF@DOX with homotypic targeting capability, we coated the PCa cell membrane (DU145 cell membrane, DCM) onto the surface of GDY-CuMOF@DOX, thus obtaining a biomimetic nanoplatform (DCM@GDY-CuMOF@DOX). The nanoplatform was characterized by using transmission electron microscope, atomic force microscope, X-ray diffraction, etc. Drug release behavior, antitumor effects in vivo and in vitro, and biosafety of the nanoplatform were evaluated.Results: We found that GDY-CuMOF exhibited a remarkable capability to load DOX mainly through π-conjugation and pore adsorption, and it responsively released DOX and generated Cu+ in the presence of glutathione (GSH). In vivo experiments demonstrated that this nanoplatform exhibits remarkable cell-killing efficiency by generating lethal reactive oxygen species (ROS) and mediating cuproptosis. In addition, DCM@GDY-CuMOF@DOX effectively suppresses tumor growth in vivo without causing any apparent side effects.Conclusion: The constructed DCM@GDY-CuMOF@DOX nanoplatform integrates tumor targeting, drug-responsive release and combination with cuproptosis and chemodynamic therapy, offering insights for further biomedical research on efficient PCa treatment. Keywords: graphdiyne, biomimetic nanoplatform, cuproptosis, chemotherapy, prostate cancer

Zhihui Wu,1– 3 Junyao Song,4 Xiyou Chen,1 Daoqun Ding,1– 3,5 Xiangyi Zhang1,6 1Department of Psychology, School of Education Science, Hunan Normal University, Changsha, People’s Republic of China; 2Institute of Interdisciplinary Studies, Hunan Normal University, Changsha, People’s Republic of China; 3Center for Mind and Brain Science, Hunan Normal University, Changsha, People’s Republic of China; 4School of Psychology, Central China Normal University, Wuhan, People’s Republic of China; 5Research Base for Mental Health Education of Hunan Province, Changsha, People’s Republic of China; 6Cognition and Human Behavior Key Laboratory of Hunan Province, Hunan Normal University, Changsha, People’s Republic of ChinaCorrespondence: Daoqun Ding; Xiangyi Zhang, Department of Psychology, School of Education Science, Hunan Normal University, 36 Lushan Road, Changsha, Hunan, 410081, People’s Republic of China, Email psychding@hunnu.edu.cn; xiangyizhang@hunnu.edu.cnPurpose: Adverse childhood experiences (ACEs) have been associated with various aspects of morality, but their precise impact on moral decision-making remains unclear. This study aims to explore how ACEs influence moral decision-making in sacrificial dilemmas.Methods: Study 1 employed traditional dilemma analysis to quantify utilitarian responses and compare them among groups with no, low, and high ACEs. Study 2 utilized the CNI model to quantify three determinants of moral decision-making: sensitivity to consequences (C parameter), sensitivity to norms (N parameter), and general action tendencies (I parameter). Differences in these parameters among groups with no, low, and high ACEs were investigated.Results: Both Study 1 and Study 2 revealed that the high-ACE and low-ACE groups showed significantly higher utilitarian responses compared to the no-ACE group. However, no notable differences emerged between the high-ACE and low-ACE groups. Study 2 found that the N parameter was significantly lower in the high-ACE group compared to the low and no-ACE groups. Similarly, the low-ACE group exhibited significantly lower scores in the N parameter compared to the no-ACE group. Additionally, no significant differences were observed in the C and I parameters among groups with no, low, and high ACEs.Conclusion: These findings suggest that individuals with a high number of ACEs tend to exhibit more utilitarian responses, attributed to decreased affective response to the violation of moral rules, rather than increased deliberative cost-benefit reasoning or a general preference for action. Such insights deepen our understanding of the precise aspects of moral decision-making influenced by ACEs.Keywords: adverse childhood experiences, moral decision-making, CNI model

Zhenzhu Wu,1 Jie Li,1 Peipei Fang,1 Chenwei Pan,1 Yi Chen2 1Department of Infectious Disease, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, People’s Republic of China; 2Department of Gastroenterology, Wenzhou People’s Hospital, Wenzhou, Zhejiang, 325000, People’s Republic of ChinaCorrespondence: Yi Chen; Zhenzhu Wu, Email alivefish1993@qq.com; 15003890524@163.comBackground: The prevalence of pyogenic liver abscess (PLA) is increasing worldwide. However, evaluation on its economic burden is still lack.Methods: A retrospective study that included all patients identified PLA from 2017 to 2020 was conducted. Clinical information and hospital costs were collected through the electronic medical records. We evaluated the economic burden using disability-adjusted life years (DALYs). Differences in socioeconomic burdens between Klebsiella pneumoniae-caused liver abscesses (KPLA) and non-Klebsiella pneumoniae-caused liver abscesses (non-KPLA) were compared.Results: We found 327 patients identified PLA in the study, including 146 with KPLA and 181 with non-KPLA. The demographic characteristics, median hospital stay, severity, and in-hospital mortality were similar between the two groups. The median total in-hospital cost was higher in the non-KPLA than in the KPLA group, although no statistical difference was found (&dollar;3607.2 vs &dollar;3424.6; P = 0.446). The median DALY loss was significantly higher in the KPLA than in the non-KPLA group [1.49 (0.97– 2.30) vs 1.27 (0.87– 1.89); P = 0.033)], and male patients presented a higher average DALY loss than female patients. KPLA had a substantially greater median indirect economic loss than the non-KPLA group [&dollar;1442.8 (915.9– 17,221.5) vs &dollar;1232.5 (764.6– 15,473.0); P = 0.028], and indirect economic loss exhibited a significant increase from 2017 to 2020 in patients with PLA. No differences were found in the socioeconomic burden between the two groups [&dollar;8019.6 (4200.3– 21,832.1) vs &dollar;7436.4 (4023.2– 19,063.9); P = 0.172].Conclusion: The economic burden of PLA is significant, particularly in patients with KP. Patients with KPLA experienced increased DALY loss and indirect economic loss than non-KPLA. PLA must be prioritized as the indirect economic burden rises annually.Keywords: pyogenic liver abscess, Klebsiella pneumoniae, socioeconomic burden, disability-adjusted life years

Yang Zhao,1 Hua Wang,2 Zhengjun Wu,1 Yunxiang Zhu,1 Jingsong Wang1 1Department of Pharmacy, Guangyuan Central Hospital, Guangyuan, Sichuan, People’s Republic of China; 2Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Jingsong Wang, Department of Pharmacy, Guangyuan Central Hospital, Guangyuan, Sichuan, People’s Republic of China, Email wjs5515@163.comBackground: Adverse reactions induced by isoosmolar contrast medium (iodixanol) are mostly mild, with rashes and headaches being the most common. Although anaphylactic shock has been reported, no related incidents have been documented on cerebral angiography.Objective: This article reports a serious case of anaphylactic shock possibly induced by iodixanol and provides an overview of the case report.Case Summary: A 65-year-old female with persistent headaches for nearly six months and CTA examination revealed multiple intracranial aneurysms. After two treatments, she returned to the hospital for aneurysm of reexamination a month ago. Following a preoperative assessment, cerebral angiography was performed. Three minutes after the procedure, the patient experienced dizziness, increased heart rate, followed by hypotension (BP 90/43 mm Hg), a sudden drop-in heart rate (HR 68 bpm), and a drop in SpO2 to 92%. Intravenous dexamethasone for anti-allergic were administered immediately, along with therapy through oxygen-inhalation. However, the patient then developed limb convulsions, unresponsiveness, and was urgently given diazepam for sedation and sputum aspiration to maintain airway patency. Blood pressure decrease to 53/29 mm Hg, and SpO2 readings were unavailable. Intravenous dopamine to elevates blood pressure, and assists breathing by intubating in the endotracheal. After 3 minutes, as the blood pressure remained undetectable, intermittent intravenous epinephrine 1mg was administered to raise the blood pressure, gradually restoring it to 126/90 mm Hg, and SpO2 increased to 95%. The patient was diagnosed with iodixanol-induced anaphylactic shock and urgently transferred to the NICU for monitoring and treatment. The patient died despite immediate treatment.Conclusion: A 65-year-old female developed serious anaphylactic shock during cerebral angiography after receiving iodixanol. Although iodixanol is considered one of the safest iodinated contrast mediums (ICM), clinicians should be aware of its the potential for serious hypersensitivity reactions that can lead to fatal and life-threatening events.Keywords: iodixanol, cerebral angiography, hypersensitivity reaction, anaphylactic shock

Xiang Tan,&ast; Zuotao Wu,&ast; Mingwu Chen Department of Thoracic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingwu Chen, Department of Cardio-Thoracic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Email chen535@126.comAbstract: Previous case reports have demonstrated the effectiveness of combination therapy involving EGFR TKI, BRAF inhibitor dabrafenib, and MEK inhibitor trametinib in metastatic non-small-cell lung cancer (NSCLC) patients with acquired BRAF V600E and EGFR mutations. However, the current literature does not provide any reports on the presence of resistant mutations in response to the administration of three-drug combination therapy. Exploring the resistance mechanism of targeted therapy is helpful to optimize the subsequent treatment strategy of patients. Herein, we report a case of a patient with advanced EGFR positive lung adenocarcinoma harboring an acquired BRAF V600E mutation who responded to the combination of furmonertinib, dabrafenib, and trametinib therapy. Unexpectedly, a MAP2K1 K57N acquired mutation was identified by NGS (Next-generation sequencing) analysis of re-biopsy tumor tissue after the patient was resistant to three-drug therapy. As far as we know, this is the first report demonstrating that the efficacy of using combination of furmonertinib and BRAF/MEK inhibitors and the MAP2K1 K57N mutation serves as a resistant mechanism to the three-drug therapy. This novel finding not only revealed a new resistant mutation but also had important implications for the identification of effective patients to EGFR/BRAF/MEK combination therapy.Keywords: MAP2K1, furmonertinib, lung adenocarcinoma, EGFR, mutation

Yingfan Chen,1,2,&ast; Zhenhui Wu,3,&ast; Shaodan Li,2 Qi Chen,2 Liang Wang,2 Xiaorong Qi,1 Chujiao Tian,1 Minghui Yang2 1Medical School of Chinese People’s Liberation Army, Beijing, People’s Republic of China; 2Department of Traditional Chinese Medicine, the Six Medical Center of Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China; 3College of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Minghui Yang, Department of Traditional Chinese Medicine, the Six Medical Center, Chinese People’s Liberation Army General Hospital, 6 Fucheng Road, Beijing, 100048, People’s Republic of China, Tel +86-10-66939651, Email ymh9651@sina.comMethods: Related studies on PD and ferroptosis were searched in Web of Science Core Collection (WOSCC) from inception to 2023. VOSviewer, CiteSpace, RStudio, and Scimago Graphica were employed as bibliometric analysis tools to generate network maps about the collaborations between authors, countries, and institutions and to visualize the co-occurrence and trends of co-cited references and keywords.Results: A total of 160 original articles and reviews related to PD and ferroptosis were retrieved, produced by from 958 authors from 162 institutions. Devos David was the most prolific author, with 9 articles. China and the University of Melbourne had leading positions in publication volume with 84 and 12 publications, respectively. Current hot topics focus on excavating potential new targets for treating PD based on ferroptosis by gaining insight into specific molecular mechanisms, including iron metabolism disorders, lipid peroxidation, and imbalanced antioxidant regulation. Clinical studies aimed at treating PD by targeting ferroptosis remain in their preliminary stages.Conclusion: A continued increase was shown in the literature within the related field over the past decade. The current study suggested active collaborations among authors, countries, and institutions. Research into the pathogenesis and treatment of PD based on ferroptosis has remained a prominent topic in the field in recent years, indicating that ferroptosis-targeted therapy is a potential approach to halting the progression of PD.Keywords: Parkinson’s disease, ferroptosis, bibliometric analysis, iron accumulation, alpha-synuclein, mitochondrial dysfunction, oxidative stress, lipid peroxidation

Zeyu Wu,1,&ast; Yan Li,1,&ast; Min Jiang,1 Lixuan Sang,2 Bing Chang1 1Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lixuan Sang, Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China, Email sanglixuan2008@163.com Bing Chang, Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China, Email cb000216@163.comBackground: Inflammatory bowel disease (IBD) is a chronic recurrent gastrointestinal inflammatory disease. Selenium has been reported to have therapeutic potential in IBD. Selenium yeast is a common selenium supplement that is convenient to access. This study explored the effect of selenium yeast on dextran sulfate sodium- (DSS-)induced chronic colitis in mice.Methods: Mice were randomly divided into four groups: the control group, selenium yeast group, chronic colitis group, and chronic colitis+selenium yeast group (n=6). Mice were killed on the 26th day. The disease activity index (DAI) score and histological damage score were calculated. Cytokines, serum selenium, colonic tissue selenium, gut microbiota and their metabolites short-chain fatty acids (SCFAs) were evaluated.Results: Selenium yeast lowered IL-1β, IL-6, TNF-α, IL-17A, IL-22 and IFN-γ (P< 0.05). In addition, selenium yeast significantly elevated Turicibacter, Bifidobacterium, Allobaculum, Prevotella, Halomonas, Adlercreutzia (P< 0.05), and butyric acid (P< 0.05).Conclusion: Selenium yeast could improve DSS-induced chronic colitis in mice by regulating cytokines, gut microbiota and their metabolites.Keywords: selenium yeast, chronic colitis, gut microbiota, metabolism

Zhengyi Lyu,1,&ast; Qiongying Shen,1,&ast; Shuxin Tian,1,&ast; Liyan Gong,2 Haizhou Lou,3 Guanai Bao,2 Zhuoxuan Wu,3 Chao Lu,2 Weiping Zhang,4 Rui Huang,5 Conghua Ji,6 Siyi Zheng,1 Wei Pan,1 Yinyin Ying,4 Jianwei Jin,4 Yi Liang4 1The Third Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Zhejiang Cancer Hospital, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Medical Oncology, Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Acupuncture, the Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 5Department of Acupuncture and Tuina, Wenzhou Central Hospital, Wenzhou, Zhejiang, People’s Republic of China; 6Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Liang, Department of Acupuncture, the Third Affiliated Hospital of Zhejiang Chinese Medical University, 219 Moganshan Road, Hangzhou City, Zhejiang Province, 310053, People’s Republic of China, Email liangyiwww@126.comBackground: Transcutaneous Electrical Acupoint Stimulation (TEAS) therapy opens up the possibility for individuals with Cancer-induced bone pain (CIBP) to receive a home-based, patient-controlled approach to pain management. The aim of this study is designed to evaluate the efficacy of patient-controlled TEAS (PC-TEAS) for relieving CIBP in patients with non-small cell lung cancer (NSCLC).Methods/Design: This is a study protocol for a prospective, triple-blind, randomized controlled trial. We anticipate enrolling 188 participants with NSCLC bone metastases who are also using potent opioid analgesics from 4 Chinese medical centers. These participants will be randomly assigned in a 1:1 ratio to either the true PC-TEAS or the sham PC-TEAS group. All participants will receive standard adjuvant oncology therapy. The true group will undergo patient-controlled TEAS intervention as needed, while the sham group will follow the same treatment schedule but with non-conductive gel patches. Each treatment course will span 7 days, with a total of 4 courses administered. There will be 4 assessment time points: baseline, the conclusion of weeks 4, 8, and 12. The primary outcome of this investigation is the response rate of the average pain on the Brief Pain Inventory (BPI) scale at week 4 after treatment. Secondary outcomes include pain related indicators, quality of life scale, mood scales, and routine blood counts on the assessment days. Any adverse events will be promptly addressed and reported if they occur. We will manage trial data using the EDC platform, with a data monitoring committee providing regular quality oversight.Discussion: PC-TEAS interventions offer an attempt to achieve home-based acupuncture treatment and the feasibility of achieving triple blinding in acupuncture research. This study is designed to provide more rigorous trial evidence for the adjuvant treatment of cancer-related pain by acupuncture and to explore a safe and effective integrative medicine scheme for CIBP.Trial Registration: ClinicalTrials.gov NCT05730972, registered February 16, 2023.Keywords: bone cancer pain, TEAS, transcutaneous electrical nerve stimulation, patient-controlled analgesia, integrative medicine, home-based treatment

Qingqing Luo,1,&ast; Yibo Quan,1,&ast; Wei Liu,1 Zixin Wu,1 Wenjing Qiu,1 Wenlong Liang,1 Ping Yang,1 Qing Huang,1 Guanwei Li,1 Jianchang Wei,1 Qiang Wang,1 Fei Shen,2 Wanglin Li,1 Feng He,3 Jie Cao1 1Department of Gastrointestinal Surgery, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China; 2Department of Thyroid Surgery, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China; 3Department of Nephrology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Cao, Department of Gastrointestinal Surgery, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China, Email eycaojie@scut.edu.cn Feng He, Department of Nephrology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China, Email eyhefeng@scut.edu.cnPurpose: Consensus molecular subtypes (CMS) are mainly used for biological interpretability and clinical stratification of colorectal cancer (CRC) in primary tumors (PT) but few in metastases. The heterogeneity of CMS distribution in metastases and the concordance of CMS between PT and metastases still lack sufficient study. We used CMS to classify CRC metastases and combine it with histopathological analysis to explore differences between PT and distant metastases.Patients and Methods: We obtained gene expression profiles for 942 PT samples from TCGA database (n=376) and GEO database (n=566), as well as 442 metastasis samples from GEO database. Among these, 765 PT samples and 442 metastasis samples were confidently identified with CMS using the “CMS classifier” and enrolled for analysis. Clinicopathological manifestation and CMS classification of CRC metastases were assessed with data from GEO, TCGA, and cBioPortal. Overall, 105 PT-metastasis pairs were extracted from 10 GEO datasets to assess CMS concordance. Tumor microenvironment (TME) features between PT and metastases were analyzed by immune-stromal infiltration with ESTIMATE and xCell algorithms. Finally, TME features were validated with multiplex immunohistochemistry in 27 PT-metastasis pairs we retrospectively collected.Results: Up to 64% of CRC metastases exhibited concordant CMS groups with matched PT, and the TME of metastases was similar to that of PT. For most common distant metastases, liver metastases were predominantly CMS2 and lung and peritoneal metastases were mainly CMS4, highlighting “seed” of tumor cells of different CMS groups had a preference for metastasis to “soil” of specific organs. Compared with PT, cancer-associated fibroblasts (CAF) reduced in liver metastases, CD4+T cells and M2-like macrophages increased in lung metastases, and M2-like macrophages and CAF increased in peritoneal metastases.Conclusion: Our findings underscore the importance of CMS-guided specific organ monitoring and treatment post-primary tumor surgery for patients. Differences in immune-stromal infiltration among different metastases provide targeted therapeutic opportunities for metastatic CRC.Keywords: colorectal cancer, primary tumors, metastases, consensus molecular subtypes, tumor microenvironment

Tingting Chen,1 Zimei Wu,1,2 Qiaodan Hou,1 Yixin Mei,1 Kunkun Yang,1 Jing Xu,3 Lin Wang1,3 1School of Medicine, Southern University of Science and Technology, Shenzhen, People’s Republic of China; 2Department of Orthopedic Surgery, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, People’s Republic of China; 3Southern University of Science and Technology Hospital, Shenzhen, People’s Republic of ChinaCorrespondence: Lin Wang, Email wangl7@sustech.edu.cnPurpose: Given the escalating prevalence of diabetes, the demand for specific bone graft materials is increasing, owing to the greater tendency towards bone defects and more difficult defect repair resulting from diabetic bone disease (DBD). Melatonin (MT), which is known for its potent antioxidant properties, has been shown to stimulate both osteogenesis and angiogenesis.Methods: MT was formulated into MT@PLGA nanoparticles (NPs), mixed with sodium alginate (SA) hydrogel, and contained within a 3D printing polycaprolactone/β-Tricalcium phosphate (PCL/β-TCP) scaffold. The osteogenic capacity of the MT nanocomposite scaffold under diabetic conditions was demonstrated via in vitro and in vivo studies and the underlying mechanisms were investigated.Results: Physicochemical characterization experiments confirmed the successful fabrication of the MT nanocomposite scaffold, which can achieve long-lasting sustained release of MT. The in vitro and in vivo studies demonstrated that the MT nanocomposite scaffold exhibited enhanced osteogenic capacity, which was elucidated by the dual angiogenesis effects activated through the NF-E2–related factor 2/Heme oxygenase 1 (Nrf2/HO-1) signaling pathway, including the enhancement of antioxidant enzyme activity to reduce the oxidative stress damage of vascular endothelial cells (VECs) and directly stimulating vascular endothelial growth factor (VEGF) production, which reversed the angiogenesis-osteogenesis uncoupling and promoted osteogenesis under diabetic conditions.Conclusion: This study demonstrated the research prospective and clinical implications of the MT nanocomposite scaffold as a novel bone graft for treating bone defect and enhancing bone fusion in diabetic individuals. Keywords: diabetic bone defect, melatonin, Nrf2/HO-1 signaling pathway, dual angiogenesis effects, 3D printing

Zixia Wu,1,&ast; Weibo Xia,1,&ast; Liling Ou,1 Ling Zheng,1 Bingying Hou,1 Tonghe Pan,2 Wenjie Sun,1 Leo H Koole,1 Yongqing Shao,2 Lei Qi1 1National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, the People’s Republic of China; 2Ningbo Eye Hospital, Affiliated to Wenzhou Medical University, Ningbo, Zhejiang, 310000, the People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongqing Shao, Ningbo Eye Hospital, Affiliated to Wenzhou Medical University, Ningbo, Zhejiang, 310000, the People’s Republic of China, Tel +86-574 87862193, Email sunniesyq@163.com Lei Qi, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, the People’s Republic of China, 325027, Tel +86-577-88067973, Email imdoll@163.comPurpose: Patients afflicted with dry eye disease (DED) experience significant discomfort. The underlying cause of DED is the excessive accumulation of ROS on the ocular surface. Here, we investigated the nitrogen doped-graphene quantum dots (NGQDs), known for their ROS-scavenging capabilities, as a treatment for DED.Methods: NGQDs were prepared by using citric acid and urea as precursors through hydrothermal method. The antioxidant abilities of NGQDs were evaluated through: scavenging the ROS both extracellular and intracellular, regulating the nuclear factor-erythroid 2-related factor (Nrf2) antioxidant pathway of human corneal epithelial cells (HCECs) and their transcription of inflammation related genes. Furthermore, NGQDs were modified by Arg-Gly-Asp-Ser (RGDS) peptides to obtain RGDS@NGQDs. In vivo, both the NGQDs and RGDS@NGQDs were suspended in 0.1% Pluronic F127 (w/v) and delivered as eye drops in the scopolamine hydrobromide-induced DED mouse model. Preclinical efficacy was compared to the healthy and DPBS treated DED mice.Results: These NGQDs demonstrated pronounced antioxidant properties, efficiently neutralizing free radicals and activating the intracellular Nrf2 pathway. In vitro studies revealed that treatment of H2O2-exposed HCECs with NGQDs induced a preservation in cell viability. Additionally, there was a reduction in the transcription of inflammation-associated genes. To prolong the corneal residence time of NGQDs, they were further modified with RGDS peptides and suspended in 0.1% Pluronic F127 (w/v) to create RGDS@NGQDs F127 eye drops. RGDS@NGQDs exhibited superior intracellular antioxidant activity even at low concentrations (10 μg/mL). Subsequent in vivo studies revealed that RGDS@NGQDs F127 eye drops notably mitigated the symptoms of DED mouse model, primarily by reducing ocular ROS levels.Conclusion: Our findings underscore the enhanced antioxidant benefits achieved by modifying GQDs through nitrogen doping and RGDS peptide tethering. Importantly, in a mouse model, our novel eye drops formulation effectively ameliorated DED symptoms, thereby representing a novel therapeutic pathway for DED management.Keywords: dry eye disease, antioxidant, nitrogen doped graphene quantum dots, Nrf2 antioxidant pathway

Hongjie Cai,1 Song Chen,2 Zhiqiang Wu,1 Fan Wang,1 Shuangyan Tang,1 Ludan Chen,1 Wenbo Guo1 1Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510062, People’s Republic of China; 2Department of Minimally Invasive Interventional Therapy, Sun Yat-Sen University Cancer Center and Sun Yat-Sen University State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of ChinaCorrespondence: Wenbo Guo, Email guowenbo@mail.sysu.edu.cnPurpose: Local in combination with systemic therapy might be an option for patients with advanced unresectable hepatocellular carcinoma (uHCC). This study examined the clinical benefits and adverse events (AEs) of first-line transarterial embolization (TAE) and hepatic arterial infusion chemotherapy (HAIC) combined with atezolizumab (Atezo) and bevacizumab (Bev) in patients with uHCC of a diameter larger than 8 cm.Patients and methods: This retrospective study included patients with uHCC of a diameter larger than 8 cm who were treated with first-line Atezo-Bev and TAE+HAIC at the First Affiliated Hospital of Sun Yat-Sen University between September 30, 2019, and September 30, 2022. Progression-free survival (PFS), overall survival (OS), tumor response according to mRECIST, and AEs were analyzed. Multivariable Cox analyses were performed to examine the factors associated with PFS.Results: Thirty patients were included. The objective response rate (ORR) was 74.4% (95% confidence interval [CI], 59.3%-89.5%), and the disease control rate (DCR) was 93.3% (95% CI, 85.4%-98.6%). The median follow-up was 11.4 (inter-quartile range [IQR], 5.5– 17.9) months. The median PFS was 6.8 (95% CI, 2.6– 11.1) months. The 3-, 6-, 9-, and 12-month survival rates were 86.2%, 82.5%, 68.6%, and 60%, respectively. The median OS was not estimated. Extrahepatic metastasis was independently associated with PFS (hazard ratio [HR]=3.468, 95% CI, 1.001– 12.023). The most common AEs were fever (46.7%). Grade 4 AEs occurred one time as hematemesis but no 5 AEs were observed.Conclusion: Atezo-Bev combined with TAE and HAIC might benefit patients with uHCC of a diameter larger than 8 cm, with manageable AEs.Keywords: immune checkpoint inhibitors, tyrosine kine inhibitors, local therapy, systemic therapy, large unresectable hepatocellular carcinoma

Zhijian Wu,1– 3 Xiaotian Jin,1 Ilyas Tudahun,1 Shangjie Wu,2,3 Mingxian Chen,1 Jianjun Tang1 1Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, 410011, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 3Hunan Centre for Evidence-Based Medicine, Changsha, 410011, People’s Republic of ChinaCorrespondence: Jianjun Tang; Mingxian Chen, Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, No. 139 Middle Renmin Road, Furong District, Changsha, Hunan, 410011, People’s Republic of China, Fax + 86 731 85533525, Email tom200210@csu.edu.cn; xymingxianchen@csu.edu.cnBackground and Aims: Whether IMH can directly cause persistent myocardial necrosis after reperfusion therapy in STEMI patients is still unclear. We conducted a prospective study to compare the cardiovascular parameters in patients with STEMI with and without IMH to explore the potential correlations between IMH and poor outcomes.Methods and Results: We prospectively enrolled 65 consecutive patients with newly diagnosed STEMI admitted to the CCU of the Second Xiangya Hospital of Central South University between April 2019 and November 2021, all of whom underwent primary PCI. Of these, 38 (58.5%) and 27 (41.5%) patients were in the IMH-absent and IMH-present groups, respectively. At a mean time of 5– 7 days after reperfusion therapy, the volume of MI measured using LGE sequence was larger in STEMI patients with IMH than in patients without IMH (34.2 ± 12.7 cm3 vs 21.1 ± 13.1 cm3, P< 0.001). HsTNT levels were significantly higher in the IMH-present group than in the IMH-absent [2500.0 (1681.5– 4307.0) pg/mL vs 1710.0 (203.0– 3363.5) pg/mL, P=0.021] group during hospitalization. The LVEF measured using CMR in the IMH-present group was lower than that in the IMH-absent group (30.7 ± 9.8% vs 42.3 ± 11.0%, P < 0.001). The rate of MACE at 12 months in IMH-present group was significantly higher than in the IMH-absent group (9/27 VS 2/38, P = 0.012).Conclusion: IMH can lead to further expansion of MI volumes in patients with STEMI, resulting in lower LVEF and higher MACE rate in the post-discharge follow-up.Keywords: myocardial infarction, cardiac magnetic resonance, intramyocardial hemorrhage, infarction volume, outcome

Ping Shao,1 Danyang Dong,1 Yong Huang,2 Yan Wang,1 Lian Pan,3 Qunshan Zhu,2 Zheng Wu,2 Fengjuan Jiang,4 Wei Wei2 1Department of Spleen and Stomach Diseases, Yixing Traditional Chinese Medicine Hospital, Wuxi, 214200, People’s Republic of China; 2Department of General Surgery, Jiangdu People’s Hospital Affiliated to Yangzhou University, Yangzhou, 225200, People’s Republic of China; 3Pathology Department, Yixing Traditional Chinese Medicine Hospital, Wuxi, 214200, People’s Republic of China; 4Department of Gastroenterology, Jiangdu People’s Hospital Affiliated to Yangzhou University, Yangzhou, 225200, People’s Republic of ChinaCorrespondence: Wei Wei, Email 18952531159@yzu.edu.cnBackground: Gastric cancer (GC) as is the second deadliest malignancy still lacks rapid, simple and economical detection and early clinical screening techniques. Surface-enhanced Raman spectroscopy (SERS) is a spectroscopic technique based on the surface plasmon resonance of precious metal nanoparticles, which can effectively detect low-abundance tumor markers. Combining SERS technology with sensors has high potential in the diagnosis and screening of GC.Methods: A novel Au/Si nano-umbrella array (Au/SiNUA) was prepared as a SERS substrate and the substrate was functionalized using the corresponding tumor marker aptamers for the detection of clinical biological samples using a one-step recognition release mechanism. Optimization of aptamer and complementary chain concentrations and detection time for optimal sensor preparation.Results: Au/SiNUA were tested to have good SERS enhancement activity. The proposed aptamer biosensor has good specificity and stability, with a low detection time of 18 min and a limit of detection (LOD) at the fM level, which is superior to most of the methods reported so far; and the accuracy of the clinical assay is comparable to that of the ELISA method. The expression levels of PDGF-B and thrombin in the serum of GC patients and healthy individuals can be effectively detected and differentiated.Conclusion: The ultrasensitive and specific aptamer biosensor is highly feasible for the diagnosis and screening of GC and has good application prospects.Keywords: surface-enhanced Raman scattering, gastric cancer, aptamer, biosensor, Au/SiNUA

Yanchao Xu,1,&ast; Yunzheng Li,2,&ast; Yanjun Lu,3,&ast; Weihong Wang,1 Zhaowu Lian,3 Zijie Wu,4 Binghua Li,1 Decai Yu1– 3 1Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, People’s Republic of China; 2State Key Laboratory of Pharmaceutical Biotechnology, Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, People’s Republic of China; 3Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 4Jiangsu Key Laboratory of Druggability of Biopharmaceuticals and State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Binghua Li; Decai Yu, Tel +86025-83106666, Fax +86025-68183912, Email lbhnju@163.com; yudecai@nju.edu.cnBackground: Hepatocellular carcinoma (HCC) is one of the most serious malignant tumors threatening human life with a high mortality rate. The liver regenerative capacity after hepatectomy in early-stage HCC patients is influenced by various factors, including surgical methods and energy metabolism. This study aims to provide a prognostic model based on genes related to liver regeneration that can predict the prognosis of non-tumor tissues in HCC patients.Patients and Methods: A total of 584 non-tumor tissues from HCC patients were collected from three independent databases. Kaplan-Meier survival curves were used to identify prognostic liver-regeneration genes. Subsequently, a prognostic indicator, designated as the Liver Regeneration score (LR score), was determined using single-sample gene set enrichment analysis (ssGSEA). Independent cohorts were used to verify the relationship between LR score and prognosis in non-tumor tissues of HCC patients. Furthermore, a liver regeneration-related model was established to validate key genes identified through LASSO Cox regression analysis.Results: We constructed a gene set comprising 24 liver regeneration-related genes, and the LR score was utilized to predict the prognosis of HCC patients based on its levels in non-tumor tissues. In non-tumor tissues of HCC patients, higher LR scores were associated with improved prognosis. Higher LR scores in non-tumor tissues indicate improved liver metabolism in HCC patients, revealed by Enrichment analysis. LASSO Cox regression analysis identified two key genes, DHTKD1 (dehydrogenase E1 and transketolase domain containing 1) and PHYH (phytanoyl-CoA 2-hydroxylase), and higher expression levels of these genes in non-tumor tissues were correlated with better prognosis. The expression levels of these two genes also changed corresponding to the progression of liver regeneration.Conclusion: In summary, our study has introduced a novel LR gene signature for HCC patients, providing a predictive model for estimating clinical prognosis from non-tumor tissues. The LR score demonstrates promise as a reliable indicator for predicting overall survival in HCC.Keywords: hepatocellular carcinoma, HCC, non-tumor tissue, liver regeneration, prognosis

Meng Sun,1– 3,&ast; Zhouyang Wu,1– 3,&ast; Rong Wang,1– 3 Rui Xia,1– 3 Yi Sun,1– 3 Elham Esmaeili,1– 3 Zhengyuan Xia,4,5 Zhilin Wu,1– 3 Tingting Wang1– 3 1Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, People’s Republic of China; 4State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, People’s Republic of China; 5Department of Anesthesiology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tingting Wang; Zhilin Wu, Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Tel +862785351643, Email wangtt201307@163.com; 840916@qq.comBackground: Erector spinae plane block (ESPB) is an easy and safe method for postoperative analgesia. However its effect lasts only for several hours. This trial was to investigate the effectiveness of different doses of nalbuphine as an adjuvant to ropivacaine in ESPB for patients undergoing percutaneous nephrolithotomy (PCNL).Methods: Patients scheduled for PCNL were randomized into three groups and received ultrasound-guided ESPB at T10 level for postoperative analgesia. Each subject received 28 mL of 100 mg ropivacaine solution mixed with 2 mL of normal saline (Group R), 2 mL of 10 mg nalbuphine (Group RNL), or 2 mL of 20 mg nalbuphine (Group RNH). Primary outcome was the time to first opioid demand. Secondary outcomes were morphine consumption, VAS scores within 24 h postoperatively, rescue analgesic requirements, and length of hospital stay.Results: The median [interquartile range, IQR] time to first opioid demand was significantly longer in group RNH (8.70 [6.90,14.85] h) than that of group R and group RNL (2.90 [2.00,6.30] h and 5.80 [2.95,7.00] h, respectively). VAS scores (either resting or active) within 24 h postoperatively were comparable between the three groups, with the most significant differences especially at 4, 6, 8 h. Morphine consumption at 24 h postoperatively was significant for R group vs RNH group (median difference, 9; 95% confidence interval [CI], 1.57 to 16.43; p = 0.02).Conclusions: Adding 20mg nalbuphine to ropivacaine in ESPB could significantly improve the effect of analgesia and prolong the duration of nerve blocks for PCNL.Keywords: adjuvant, erector spinae plane block, nalbuphine, percutaneous nephrolithotomy, postoperative pain

Na Li,1 Xiaochun Jiang,2 Wanju Zhang,1 Wenping Xiao,1 Zhaona Wu,1 Huirong Wang,1 Feng He1 1Li Shizhen College of Traditional Chinese Medicine, Huanggang Normal University, Huanggang, 438000, People’s Republic of China; 2Hubei Key Laboratory for Processing and Application of Catalytic Materials, College of Chemistry and Chemical Engineering, Huanggang Normal University, Huanggang, 438000, People’s Republic of ChinaCorrespondence: Na Li; Feng He, Email ln19860622@126.com; hfeng@hust.edu.cnIntroduction: Combined multimodal therapy for breast cancer is a promising therapeutic approach to increase treatment efficacy and reduce systemic toxicity. The present study aimed to develop a novel multifunctional drug release nanoplatform based on RGD-conjugated hyaluronic acid (HA)-functionalized copper sulfide (CuS) for activatable dual-targeted synergetic therapy against cancer.Methods: The pH and NIR-responsive dual-targeting nanoplatform CuS:Ce6@HA:DOX@RGD was prepared, characterized, and evaluated for its stability and photodynamic and photothermal properties. The loading and release of the drug were measured at different pH values with or without laser radiation using the dialysis method. The cellular uptake of the platform specifically by the tumor cells treated with different formulations was investigated through fluorescence imaging. The in vitro and in vivo biosafety levels were assessed systematically. Finally, the antitumor efficiencies against breast cancer were assessed via in vitro and in vivo experiments.Results: The spheroid CuS:Ce6@HA:DOX@RGD exhibited remarkable stability and monodispersity in solution. The photosensitive CuS and Ce6 could simultaneously absorb the near-infrared light efficiently to convert NIR light to fatal heat and to generate reactive oxygen species. The CuS:Ce6@HA:DOX@RGD dissociated under an acid environment, causing the release of DOX into the tumor to accelerate upon laser irradiation. The CuS:Ce6@HA:DOX@RGD exhibited target-specific and strong binding ability via a synergic CD44/αvβ3 receptor-mediated bimodal targeting, which led to improved therapeutic efficacy. The tumor growth was effectively inhibited using synergetic photodynamic/photothermal/chemo therapy. No evident systemic toxicity was noted during treatment.Conclusion: The newly prepared CuS:Ce6@HA:DOX@RGD has great potential as an activatable theranostic nanoplatform for efficient dual-targeted synergistic therapy against breast cancer. Keywords: responsive nanoplatform, targeting, drug delivery, synergistic therapy, breast cancer

Haibang Pan,1,&ast; Tianming Wang,1,2,&ast; Ying Che,3,4 Xiaoli Li,1,5 Yan Cui,1 Quanxin Chen,1 Zhihang Wu,1 Jianfeng Yi,1 Bo Wang3 1First School of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of China; 2Gansu Provincial Key Laboratory of Traditional Chinese Medicine Recipe Mining and Innovation Transformation, Gansu Province New Production of Traditional Chinese Medicine Product Creation Engineering Laboratory, Lanzhou, People’s Republic of China; 3School of Nursing, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of China; 4Research Ward, Gansu Provincial People’s Hospital, Lanzhou, People’s Republic of China; 5Gansu Provincial Maternity and Child-Care Hospital, Lanzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Wang; Jianfeng Yi, Email wbbphb@gszy.edu.cn; yijf02@163.comIntroduction: Skin and soft tissue infection (SSTI) is a frequently encountered clinical disease, and Sanhuang ointment, a traditional Chinese medicine, is used to treat it. However, the pharmacological effect of Sanhuang ointment on SSTI and its underlying mechanism remains unclear. Here, we investigate the protective effect of Sanhuang ointment on Methicillin-resistant Staphylococcus aureus (MRSA) infection in the skin and soft tissues and the underlying mechanism by network pharmacological analysis, followed by in vivo experimental validation.Methods: Via network pharmacology, the active components and disease targets of Sanhuang ointment were screened and intersected for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A rat model of skin and soft tissue infection was established, and pathological features were observed. Large, medium, and small-dose groups (1 g, 0.5 g, and 0.25 g/animal, with the total amount of Vaseline, dispensed 1 g/animal) of Sanhuang ointment were prepared and Mupirocin ointment was used as a positive control (0.5 g/animal, with the total amount of Vaseline, dispensed 1 g/animal). The expressions of key proteins of the IL-17/NF-κB signaling pathway and downstream inflammatory factors were analyzed by histomorphological analysis, enzyme-linked immunosorbent assay, polymerase chain reaction, and Western blotting.Results: In all, 119 active components and 275 target genes of Sanhuang ointment were identified and intersected with MRSA infection-related genes via network pharmacology analysis, and 34 target genes of Sanhuang ointment were found to be involved in skin and soft tissue infections with MRSA. Sanhuang ointment (1 g/mouse) could effectively ameliorate histopathological changes and significantly inhibit the expression of key proteins involved in the IL-17/NF-κB signaling pathway and downstream inflammatory factors (p < 0.05).Conclusion: Sanhuang ointment has a protective effect on MRSA infection and inhibits inflammation by inhibiting the IL-17/NF-κB signaling pathway. Our findings are important for the secondary development and new drug development of Sanhuang ointment.Plain Language Summary: Sanhuang ointment can significantly inhibit inflammatory response after skin and soft tissue infection with MRSA.Sanhuang ointment may inhibit the inflammatory response induced by MRSA in the skin and soft tissue infections by targeting the IL-17/NF-κB signaling pathway.We study the active components and mechanism of action of Sanhuang ointment on MRSA infection through network pharmacology.Keywords: Sanhuang ointment, MRSA, SSTI, network pharmacology, IL-17, NF-κB

Ling Chen,1 Zujian Wu,1 Chi Guo,1 Guoping Wang,1 Kui Tu,2 Jichang Jiang2 1General Surgery, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang Province, 310012, People’s Republic of China; 2General Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, 563000, People’s Republic of ChinaCorrespondence: Jichang Jiang, Email 719182702@qq.comObjective: This study aimed to assess the efficacy of Endoscopic Retrograde Cholangiopancreatography (ERCP), common bile duct exploration, and percutaneous transhepatic cholangiography combined with common bile duct exploration for treating choledocholithiasis with acute cholangitis, to guide management strategies.Methods: A retrospective evaluation was conducted on a cohort of 283 inpatients diagnosed with choledocholithiasis and acute cholangitis at the affiliated hospital. Patients were categorized into three groups: Group A (ERCP group), Group B(common bile duct exploration group), and Group C(PTCD combine common bile duct exploration group.) Parameters such as hepatic function recovery, inflammation level control, blood loss, postoperative hospital duration, and postoperative complications were compared.Results: All groups exhibited notable reductions in postoperative biochemical parameters including alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TBIL), and WBC (P < 0.05). Group A had the least blood loss(P < 0.05), and shortest hospital stay(P < 0.05), but a higher incidence of pancreatitis(P < 0.05), with a total of 8 cases occurred(7.3%). Group C had a shorter hospital stay compared to Group B(P < 0.05).Conclusion: For patients with fewer and smaller common bile duct stones and milder symptoms, it is recommended to primarily choose endoscopic retrograde cholangiopancreatography (ERCP), endoscopic sphincterotomy (EST), and endoscopic nasobiliary drainage (ENBD), it procedures offer quicker recovery and cause minimal trauma. For patients with numerous, larger common bile duct stones but stable conditions, bile duct exploration is recommended. For those with severe conditions and significant inflammation, PTCD and common bile duct exploration are advised.Keywords: choledocholithiasis, acute cholangitis, ERCP, PTCD

Bai-Wen Zhang,1 Hao Dong,1 Zhe Wu,1 Xi Jiang,2 Wei Zou3 1Heilongjiang University of Chinese Medicine, Harbin, 150040, People’s Republic of China; 2Jinzhou Medical University, Jinzhou, 121001, People’s Republic of China; 3The Third Department of Acupuncture and Moxibustion, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, 150040, People’s Republic of ChinaCorrespondence: Wei Zou, The Third Department of Acupuncture and Moxibustion, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, 150040, People’s Republic of China, Tel +86 0451-82161746, Email weizouzw@126.comAbstract: Neuralgia is a frequently occurring condition that causes chronic pain and burdens both patients and their families. Earlier research indicated that anti-inflammatory treatment, which was primarily utilized to address conditions like neuralgia, resulted in positive outcomes. However, recent years have witnessed the emergence of various novel mechanisms associated with pain-related disorders. This review provides a concise overview of the inflammatory mechanisms involved in neuralgia. It also examines recent advancements in research, exploring the influence of ion channels and synaptic proteins on neuralgia and its complications. Additionally, the interactions between these mechanisms are discussed with the aim of suggesting innovative therapeutic approaches and research directions for the management of neuralgia.Keywords: neuralgia, inflammatory mechanisms, innovative therapeutic approaches

Jiawei Cai,1– 3,&ast; Chao He,4,&ast; Jiaheng Xu,1– 3,&ast; Qiu He,1– 3 Jinye Su,1– 3 Zanyi Wu,1– 3 Yawen Xu1– 3 1Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Neurosurgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China; 3Fujian Provincial Institutes of Brain Disorders and Brain Sciences, First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China; 4Department of Neurosurgery, Zhuji Affiliated Hospital of Wenzhou Medical University, Zhuji, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yawen Xu; Zanyi Wu, Department of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou, Fujian, 350005, People’s Republic of China, Email xuyawen121314@163.com; kirby98@126.comObjective: To identify whether intracranial hematoma (ICH) evacuation improves the prognosis of patients with ruptured anterior communicating artery (AcomA) aneurysms concomitant with small ICHs (≥ 10 mL and < 25 mL).Methods: Data on patients diagnosed with small ICHs secondary to ruptured AcomA aneurysms who underwent surgery in our department between January 2010 and February 2018 was retrospectively analyzed. The patients were divided into two groups based on whether the hematoma was evacuated. The modified Rankin Scale (mRS) was used to assess prognosis six months after onset.Results: The study recruited 58 patients, 19 of whom underwent aneurysm clipping and ICH evacuation. While 33 patients underwent aneurysm clipping, 6 patients underwent coiling embolism without ICH evacuation. The average ICH volume was 15.27± 4.07 mL. In the hematoma-evacuated group, 13 (68.4%) patients had unfavorable outcomes (mRS scores of 4 to 6). In the non-evacuated hematoma group, 13 (33.3%) patients had unfavorable outcomes (P = 0.001), postoperative infarction occurred in 11 (57.9%) patients in the hematoma evacuation group and 9 (23.1%) patients in the other group (P = 0.009).Conclusion: ICH evacuation was associated with unfavorable outcomes and postoperative infarction in ruptured AcomA aneurysms with concomitant small hematomas (< 25 mL). Aneurysm clipping or coiling without ICH evacuation may be a safe and effective choice; however, further investigation is needed.Keywords: AcomA aneurysms, intracranial hematoma, infarction, prognosis, ICH evacuation

Zhongji Wu,1,&ast; Xiaowen Chen,1,&ast; Kangkang Zhang,1 Zhenwei Liu,1 Haidi Zhang,1 Zhaocong Zheng,2 Xiaodie Zhang,2 Yubiao Chen,3 Yinghui Peng,1 Hui Li,1 Kaiyin Huang,1 Sixiang Tang,1 Li Zhao,1 Dehui Chen1 1The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510000, People’s Republic of China; 2Guangzhou Medical University, Guangzhou, 510000, People’s Republic of China; 3State Key Laboratory of Respiratory Diseases, Guangzhou, 510000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dehui Chen, 151 Yanjiang West Road, Yuexiu District, Guangzhou City, Guangdong Province, 510000, People’s Republic of China, Tel +86 13922732810, Email dehuichen84@126.comBackground: Bronchiolitis obliterans (BO) is a chronic disease that can arise as a complication of severe childhood pneumonia and can also impact the long-term survival of patients after lung transplantation. However, the precise molecular mechanism underlying BO remains unclear. We aimed to identify BO-associated hub genes and their molecular mechanisms.Methods: BO-associated transcriptome datasets (GSE52761, GSE137169, and GSE94557) were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). Additional bioinformatics analyses, such as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) analyses, were performed to determine functional roles and DEG-associated regulatory networks. Prediction of hub genes using the 12 algorithms available in the Cytohubba plugin of Cytoscape software was also performed. Verification was performed using the BO mouse model.Results: Our results revealed 57 DEGs associated with BO, of which 18 were down-regulated and 39 were up-regulated. The Cytohubba plugin data further narrowed down the 57 DEGs into 9 prominent hub genes (CCR2, CD1D, GM2A, TFEC, MPEG1, CTSS, GPNMB, BIRC2, and CTSZ). Genes such as CCR2, TFEC, MPEG1, CTSS, and CTSZ were dysregulated in 2,3-butanedione-induced BO mice, whereas TFEC, CTSS, and CTSZ were dysregulated in nitric acid-induced BO mouse models.Conclusion: Our study identified and validated four novel BO biomarkers, which may allow further investigation into the development of distinct BO diagnostic markers and novel therapeutic avenues.Keywords: bronchiolitis obliterans, biomarkers, pathways, transcriptome, therapeutic targets

Junlong Ma,1,2,&ast; Jie Huang,1,&ast; Chan Zou,1 Qian Wu,1 Jinlian Xie,1 Xingfei Zhang,1 Xiaoyan Yang,1 Shuang Yang,1 Ziteng Wu,3 Yan Jiang,3 Sen Yu,3 Xuqing Zhang,4 Guoping Yang,1,5 Mingyuan Li1 1The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 2Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People’s Republic of China; 3Nanjing Delova Biotech Co., Ltd., Nanjing, Jiangsu, 210042, People’s Republic of China; 4King-eagle Med Co., Ltd., Changsha, Hunan, 410013, People’s Republic of China; 5Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410013, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingyuan Li, Email lmyuan3@126.comBackground: Meloxicam is a selective cyclooxygenase-2 inhibitor used for pain relief, but its poor solubility limits its clinical applications. QP001 is a novel intravenous formulation of meloxicam developed with PEG and pH regulator to improve its solubility. This study aimed to evaluate the safety, tolerability, and pharmacokinetics of QP001 in Chinese healthy subjects.Methods: The trial consisted of three parts. Part I was a two-period crossover study to evaluate bioavailability, in which 10 healthy were either intravenously infused with 15mg QP001 (test) or orally given 15mg MobicⓇ (reference). Part II was a single-arm design to assess the pharmacokinetic (PK) characteristics after 30 mg single- and multiple-dose QP001 in 10 subjects. In part III, we investigated the PKs and tolerability of QP001 at a high dose (60 mg) in another 10 subjects. The PK parameters and treatment-emergent adverse events (TEAEs) were evaluated.Results: A total of 30 subjects were enrolled in the study. QP001 was well tolerated and safe without significant TEAEs in all three study parts. The PK characteristics of QP001 were linear following a single-dose range of 15– 60 mg (Cmax and AUC0-t were 5.82– 17.66 μg/mL and 58.08– 251.17 μg∙h/mL, respectively). After five consecutive daily 30 mg doses, the accumulation index was around 1.98, which indicated a minimal accumulation of QP001. Compared to the tablet dosage form, the relative bioavailability of QP001 reached 116.85%. Additionally, the PK profile of QP001 showed no gender difference.Conclusion: QP001 was well tolerated in healthy Chinese subjects after single ascending doses up to 60 mg and multiple-dose of 30 mg. Based on the PK and safety results, QP001 is a promising once-daily intravenous COX-2 inhibitor candidate for managing pain.Trial Registration: The trial is registered at chinadrugtrials.org.cn (ChiCTR2100047884).Keywords: meloxicam, phase I trial, pharmacokinetic, safety, novel formulation

Yifan Wang,1,2,&ast; Fen Yao,2,&ast; Shenglong Chen,3 Xin Ouyang,4 Jinhua Lan,5 Zheng Wu,2 Yirong Wang,2 Jingchun Chen,2 Xipei Wang,6,7 Chunbo Chen1 1Department of Critical Care Medicine, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, People’s Republic of China; 2School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510006, People’s Republic of China; 3Department of Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 4Department of Intensive Care Unit of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 5Department of Pharmacy, General Hospital of Southern Theatre Command, Guangzhou, 510010, People’s Republic of China; 6Research Center of Medical Sciences, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 7Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunbo Chen, Department of Critical Care Medicine, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, People’s Republic of China, Email gghccm@163.com Xipei Wang, Research Center of Medical Sciences, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China, Email xipei_wang@163.comPurpose: To develop a population pharmacokinetic model describing teicoplanin concentrations in patients hospitalized in intensive care unit (ICU) and to perform Monte Carlo simulations to provide detailed dosing regimens of teicoplanin.Methods: This single-center, prospective, observational study was conducted on 151 patients in ICU with 347 plasma samples. The population pharmacokinetics model was established and various covariates were evaluated. The probability of target attainment (PTA) of various proposal dosing regimens was calculated by Monte Carlo simulations.Results: The two-compartment model adequately described teicoplanin concentration-time data. The estimated glomerular filtration rate (eGFR) associated with systemic clearance (CL) was the only covariate included in the final model. The estimate of CL was 0.838 L/h, with the eGFR adjustment factor of 0.00823. The volume of the central compartment (Vc), inter-compartmental clearance (Q) and volumes of the peripheral compartments (Vp) were 14.4 L, 3.08 L/h and 51.6 L, respectively. The simulations revealed that the standard dosage regimen was only sufficient for the patients with severe renal dysfunction (eGFR ≤ 30 mL/min/1.73 m2) to attain target trough concentration (Cmin, PTA 52.8%). When eGFR > 30 mL/min/1.73 m2, increasing dose and the administration times of loading doses were the preferred options to achieve target Cmin based on the renal function and types of infection.Conclusion: The most commonly used standard dosage regimen was insufficient for all ICU patients. Our study provided detailed dosing regimens of teicoplanin stratified by eGFR and types of infection for ICU patients.Keywords: teicoplanin, pharmacokinetics, Monte Carlo simulation, intensive care unit, renal function

Han Li,1,&ast; Ke Su,1,&ast; Lu Guo,2,&ast; Yi Jiang,1 Ke Xu,1 Tao Gu,1 Jiali Chen,1 Zhenying Wu,1 Pan Wang,3 Xi Zhang,4 Yushan Yan,1 Siyuan Li,1 Xue Wu,1 Lei Han,5 Kun He,6 Lianbin Wen,7 Bo Li,4 Yunwei Han1 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Clinical Research Institute, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 4Department of General Surgery (Hepatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 5Department of Oncology, Affiliated Hospital of Jining Medical University, Jining, 272000, People’s Republic of China; 6Clinical Medical College, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 7Sichuan Provincial People’s Hospital, Chengdu, 610072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunwei Han; Bo Li, The Affiliated Hospital of Southwest Medical University, 25 TAIPING Street, Luzhou City, Sichuan Province, People’s Republic of China, Tel +86-830-3165598 ; +86-830-3165613, Email lanpaoxiansheng@126.com; liboer2002@126.comBackground: At present, it is not known whether targeting plus immunotherapy combined with transarterial chemoembolization (TACE) can improve the efficacy of hepatocellular carcinoma (HCC). The aim of this retrospective experiment was to explore the difference in clinical efficacy between antiangiogenic drugs plus PD-1 inhibitors combined with and without TACE.Methods: Clinical data of 145 patients with HCC who received anti-angiogenesis therapy plus PD-1 inhibitor combined with TACE (TACE-P-T) (n = 62) or anti-angiogenesis therapy combined with PD-1 inhibitor (P-T) (n = 83) in China from October 2018 to December 2022 were collected and reviewed. We used propensity matching (PSM) to create two groups with comparable baseline scores, compared their median survival time (mOS) and median progression-free survival time (mPFS), and performed subgroup analysis.Results: Before PSM, the mOS and mPFS of patients were 20.3 and 5.0 months in the triple therapy group and 13.6 and 7.4 months in the control group, respectively. After PSM, the mOS and mPFS of patients were 19.7 and 6.6 months in the triple treatment group and 10.5 and 3.7 months in the control group, respectively. Therefore, the TACE-P-T group showed better survival outcomes than P-T. In the subgroup analysis, compared with the control group, the mOS was 10.7 vs 20.3 months in the alpha fetoprotein (AFP) (≥ 400ng/mL/< 400ng/mL) group, 29.3 vs 7.4 months in the alkaline phosphatase (ALP) (≥ 125u/L/< 125u/L) group and 10.5 vs 20.0 months in the Portal vein invasion (PVTT) group.Conclusion: Antiangiogenic therapy combined with PD-1 inhibitors combined with TACE has significant survival benefits for HCC patients.Keywords: HCC, PD-1 inhibitors, antiangiogenic therapy, TACE

Song Chen,1 Feng Shi,2 Zhiqiang Wu,3 Liguang Wang,4 Hongjie Cai,3 Ping Ma,5 Yuanmin Zhou,5 Qicong Mai,2 Fan Wang,3 Shuangyan Tang,3 Wenquan Zhuang,3 Jiaming Lai,6 Xiaoming Chen,2 Huanwei Chen,4 Wenbo Guo3 1Department of Minimally Invasive Interventional Therapy, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Interventional Radiology, Guangdong Provincial People’s Hospital, Guangzhou, People’s Republic of China; 3Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Department of Hepatopancreatic Surgery, the First People’s Hospital of Foshan, Foshan, People’s Republic of China; 5Department of Oncology, the Twelfth People’s Hospital of Guangzhou, Guangzhou, People’s Republic of China; 6Center of Hepato-Pancreato-Biliary Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Huanwei Chen, Department of Hepatopancreatic Surgery, the First People’s Hospital of Foshan, Foshan, People’s Republic of China, Email chwei_fsyyy@163.com Wenbo Guo, Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China, Email guowenbo@mail.sysu.edu.cnPurpose: The current therapeutic strategies for high-risk, unresectable hepatocellular carcinoma (HCC) patients demonstrate suboptimal outcomes. This study aimed to assess the clinical efficacy of the combined approach of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and tislelizumab, either with or without transhepatic arterial embolization (TAE), in managing HCC patients with portal vein tumor thrombus (PVTT) and significant tumor load.Patients and Methods: In this multicenter retrospective study, we analyzed patients diagnosed with primary, unresectable HCC presenting with PVTT and substantial tumor load who had undergone treatment with HAIC, lenvatinib, and tislelizumab, with or without TAE (referred to as the THLP or HLP group), between January 2019 and February 2022 across four medical centers in China. The outcomes included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS).Results: The study cohort comprised 100 patients, 50 each in the THLP and HLP groups. The THLP group demonstrated a significantly superior ORR (72% vs 52%, P=0.039). However, both groups exhibited comparable DCR (88% vs 76%, P=0.118), as assessed by the modified response evaluation criteria in solid tumors. The median OS and PFS for the entire cohort were 12.5 months (95% CI, 10.9– 14.8) and 5.0 months (95% CI, 4.2– 5.4), respectively. The THLP group exhibited a significantly extended OS (median, 14.1 vs 11.3 months, P=0.041) and PFS (median, 5.6 vs 4.4 months, P=0.037) in comparison to the HLP group. The most frequently reported treatment-related adverse events included abdominal pain and nausea, both reported by 59% of patients.Conclusion: The combination of HAIC, lenvatinib, tislelizumab, and TAE was feasible in HCC patients with PVTT and high tumor burden, with tolerable safety.Keywords: hepatocellular carcinoma, transhepatic arterial embolization, hepatic arterial infusion chemotherapy, lenvatinib, tislelizumab

Jichan Shi,1,&ast; Gexin Gao,2,&ast; Jing Pan,3 Lian-Peng Wu,4 Hongye Ning,1 Zhengxin Wu,1 Xinchun Ye,1 Xiangao Jiang1 1Department of Infectious Disease, The Theorem Clinical College of Wenzhou Medical University, Wenzhou Central Hospital, Wenzhou, People’s Republic of China; 2Department of Nursing, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Geriatric Medicine, The Theorem Clinical College of Wenzhou Medical University, Wenzhou Central Hospital, Wenzhou, People’s Republic of China; 4Department of Laboratory, The Dingli Clinical Institute of Wenzhou Medical University, Wenzhou Central Hospital, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangao Jiang, Department of Infectious Disease, The Theorem Clinical College of Wenzhou Medical University, Wenzhou Central Hospital, 252 BaiLiDong Road, Wenzhou, Zhejiang, 325000, People’s Republic of China, Tel +86 13676788085, Email xiangaojiang09@163.comObjective: To evaluate the clinical value of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in detecting Nontuberculous mycobacteria (NTM).Methods: The clinical data of 172 patients with suspected NTM lung disease were collected from our hospital from January 1, 2018, to December 30, 2021. The results were compared with those of BACTEC MGIT 960 in liquid culture and gene chip. This study also utilised MALDI-TOF MS to detect macrolide (MA) and amikacin (Am) mutations.Results: One hundred thirty-seven cases of NTM pulmonary disease were confirmed by identifying the NTM gene chip in bronchoalveolar lavage fluid and/or MALDI-TOF MS detection. The positive predictive value and negative predictive value were 100% (131/131) and 85.37% (35/41), respectively, and the consistency of the two methods was high (kappa=0.899). For the drug resistance detection of MAs, the consistency rate between MALDI-TOF MS detection and drug sensitivity detection was 97.71% (128/131), the sensitivity was 81.25% (13/16) and the specificity was 100% (115/115). The positive and negative predictive values were 100% (13/13) and 93.75% (115/118), respectively. There was no coincidental consistency between the two methods, and the consistency was high (P< 0.001, kappa=0.884). For the drug resistance test of Am, the consistency rate between the MALDI-TOF MS test and the drug sensitivity test was 93.13% (122/131), the sensitivity was 93.52% (101/108), the specificity was 90.91% (21/23) and the positive predictive value and negative predictive value were 98.06% (101/103) and 75.00% (21/28), respectively. The two methods had high consistency, and the consistency was not coincidental (P< 0.001, kappa=0.781).Conclusion: Utilising MALDI-TOF MS has a good consistency with the drug resistance gene chip method and can be a rapid and effective method to identify strains and drug resistance of NTM. Therefore, it has certain clinical application value in patients with suspected NTM lung disease.Keywords: Nontuberculosis mycobacteria, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, strain identification, resistance

Xiyou Chen,1,2,&ast; Zhihui Wu,1,2,&ast; Bin Zhan,3 Daoqun Ding,1,2 Xiangyi Zhang1,4 1Department of Psychology, School of Education Science, Hunan Normal University, Changsha, People’s Republic of China; 2Center for Mind and Brain Science, Hunan Normal University, Changsha, People’s Republic of China; 3State Key Laboratory of Brain and Cognitive Sciences, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Psychology, Chinese Academy of Sciences, Beijing, People’s Republic of China; 4Cognition and Human Behavior Key Laboratory of Hunan Province, Hunan Normal University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Daoqun Ding; Xiangyi Zhang, Department of Psychology, School of Education Science, Hunan Normal University, 36 Lushan Road, Changsha, Hunan, 410081, People’s Republic of China, Email psychding@hunnu.edu.cn; xiangyizhang@hunnu.edu.cnPurpose: Although several studies have investigated the association between alexithymia and moral decision-making in sacrificial dilemmas, the evidence remains mixed. The current work investigated this association and how alexithymia affects moral choice in such dilemmas.Methods: The current research used a multinomial model (ie, CNI model) to disentangle (a) sensitivity to consequences, (b) sensitivity to moral norms, and (c) general preference for inaction versus action irrespective of consequences and norms in responses to moral dilemmas.Results: Higher levels of alexithymia were associated with a greater preference for utilitarian judgments in sacrificial dilemmas (Study 1). Furthermore, individuals with high alexithymia showed significantly weaker sensitivity to moral norms than did those with low alexithymia, whereas there were no significant differences in sensitivity to consequences or a general preference for inaction versus action (Study 2).Conclusion: The findings suggest that alexithymia affects moral choice in sacrificial dilemmas by blunting emotional reactions to causing harm, rather than through increased deliberative cost–benefit reasoning or general preference for inaction.Keywords: alexithymia, moral decision-making, deontology, utilitarianism, CNI model

Chaoyi Huang,1,2 Xinchao Miao,1,2 Jiang Li,1,2 Jieyi Liang,1,2 Junxi Xu,1,2 Zhe Wu1,2 1Department of Prosthodontics, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, People’s Republic of ChinaCorrespondence: Zhe Wu, Department of Prosthodontics, Affiliated Stomatology Hospital of Guangzhou Medical University, No. 39, Huangsha Road, Guangzhou, People’s Republic of China, Tel +86 020 8850 1980, Fax +86 020 8850 1980, Email zhewudentist@gzhmu.edu.cnIntroduction: Improving the biological sealing around dental abutments could promote the long-term success of implants. Although titanium abutments have a wide range of clinical applications, they incur esthetic risks due to their color, especially in the esthetic zone. Currently, zirconia has been applied as an esthetic alternative material for implant abutments; however, zirconia is purported to be an inert biomaterial. How to improve the biological activities of zirconia has thus become a popular research topic. In this study, we presented a novel self-glazed zirconia (SZ) surface with nanotopography fabricated by additive 3D gel deposition and investigated its soft tissue integration capability compared to that of clinically used titanium and polished conventional zirconia surfaces.Materials and Methods: Three groups of disc samples were prepared for in vitro study and the three groups of abutment samples were prepared for in vivo study. The surface topography, roughness, wettability and chemical composition of the samples were examined. Moreover, we analyzed the effect of the three groups of samples on protein adsorption and on the biological behavior of human gingival keratinocytes (HGKs) and human gingival fibroblasts (HGFs). Furthermore, we conducted an in vivo study in which the bilateral mandibular anterior teeth of rabbits were extracted and replaced with implants and corresponding abutments.Results: The surface of SZ showed a unique nanotopography with nm range roughness and a greater ability to absorb protein. The promoted expression of adhesion molecules in both HGKs and HGFs was observed on the SZ surface compared to the surfaces of Ti and PCZ, while the cell viability and proliferation of HGKs and the number of HGFs adhesion were not significant among all groups. In vivo results showed that the SZ abutment formed strong biological sealing at the abutment–soft tissue interface and exhibited markedly more hemidesmosomes when observed with a transmission electron microscope.Conclusion: These results demonstrated that the novel SZ surface with nanotopography promoted soft tissue integration, suggesting its promising application as a zirconia surface for the dental abutment.Keywords: dental abutment, self-glazed zirconia, nanotopography, adhesion molecule, soft tissue integration, 3D gel deposition

Shubin Li, Xingna Dong, Limeng Xu, Zhenli Wu Department of Geriatric Medical Center, Inner Mongolia People’s Hospital, Hohhot, 010021, People’s Republic of ChinaCorrespondence: Zhenli Wu, Email zhenliwu@126.comIntroduction: The potential effects of selenium nanoparticles (SeNPs) administration on arsenic exposure-mediated nephrotoxicity by alleviating fibrosis, inflammation, oxidative stress-related damage, and apoptosis remains more detailed investigations.Methods: After the synthesis of selenium nanoparticles (SeNPs) by sodium selenite (Na2SeO3) through a versatile and green procedure, the biosafety of SeNPs was assessed by assaying renal functions and inflammation in mice. Subsequently, nephroprotective effects of SeNPs against sodium arsenite (NaAsO2)-induced damages were confirmed by biochemical, molecular, and histopathological assays, including renal function, histological lesion, fibrosis, inflammation, oxidative stress-related damage, and apoptosis in mice renal tissues and renal tubular duct epithelial cells (HK2 cells).Results: The excellent biocompatibility and safety of SeNPs prepared in this study were confirmed by the non-significant differences in the renal functions and inflammation levels in mice between the negative control (NC) and 1 mg/kg SeNPs groups (p> 0.05). The results of biochemical, molecular, and histopathological assays confirmed that daily administration of 1 mg/kg SeNPs for 4 weeks not only ameliorated renal dysfunctions and injuries caused by NaAsO2 exposure but also inhibited the fibrosis, inflammation, oxidative stress-related damage, and apoptosis in the renal tissues of NaAsO2-exposed mice. In addition, altered viability, inflammation, oxidative stress-related damage, and apoptosis in the NaAsO2-exposed HK2 cells were effectively reversed after 100 μg/mL SeNPs supplementation.Conclusion: Our findings authentically confirmed the biosafety and nephroprotective effects of SeNPs against NaAsO2 exposure-induced damages by alleviating inflammation, oxidative stress-related damage, and apoptosis.Keywords: selenium nanoparticles, arsenite, nephroprotective, inflammation, oxidative stress, apoptosis

ZeYu Xu,1,&ast; Ou Li,1,&ast; YaTing Liang,1,&ast; ZhiBing Wu,2 Jiamei Xu,2 Ling Wang,3 Ling Li,3 YongNing Sun1 1Department of Brain and Mental Disease, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, ShangHai, 200040, People’s Republic of China; 2Department of Encephalopathy, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China; 3Department of Geriatrics, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi’an, 710003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: YongNing Sun, Shanghai University of Traditional Chinese Medicine, Shanghai, 200040, People’s Republic of China, Tel +8618930177579, Email ynsun2002@126.comBackground: Alzheimer’s disease (AD) is a common degenerative disease of the nervous system with serious impact on quality of life of patients and their families. With an aging population, AD has become a major public health problem in China and worldwide. However, the physiological and pathological mechanisms of AD have not been fully elucidated, and there is a lack of effective prevention and clinical treatment methods. Many studies have found that traditional Chinese medicine (TCM) has a good therapeutic effect on cognitive function in AD patients. Bu Shen Kai Qiao Fang (BSKQF) is one such Chinese herbal preparation used in the treatment of AD. We designed a protocol for a real-world clinical study of BSKQF combined with Donepezil hydrochloride (DH) to evaluate the efficacy and safety of this approach in the treatment of AD patients.Methods: This is a protocol for a real-world, multicenter, prospective, observational cohort study. The study will recruit 860 AD patients from four hospitals across China. Equal numbers of patients will be treated with BSKQF and DH or with DH only. The criteria for grouping are based primarily on patient preference. Outcome measures include scores on the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment Scale (MOCA) and will be recorded at baseline, and at one, two and three months after enrollment. The plasma Aβ 42 and plasma Tau levels of participating patients will also be measured by ELISA at baseline and after 3 months of treatment. Safety metrics and adverse events (AEs) of participating patients will be monitored and recorded.Discussion: This study will evaluate the clinical efficacy and safety of BSKQF in the treatment of AD. The results will provide reliable evidence for the clinical application of BSKQF in the treatment of AD.Study Registration: Trial registration: Chinese Clinical Trial Registry, NO. ChiCTR2000039670, Registered 5 November 2020 https://www.chictr.org.cn/showprojEN.html?proj=63800.Keywords: Alzheimer’s disease, Bu Shen Kai Qiao Fang, real-world trial, MMSE, MOCA, Aβ 42, tau

Han Li,1,&ast; Lu Guo,2,&ast; Ke Su,1,&ast; Changlun Li,3 Yi Jiang,1 Pan Wang,4 Jiali Chen,1 Zhenying Wu,1 Ke Xu,5 Tao Gu,1 Hao Zeng,1 Kun He,6 Hao Chi,1 Wenxi Zhao,7 Lei Han,3 Yunwei Han1 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Department of Oncology, Affiliated Hospital of Jining Medical University, Jining, 272000, People’s Republic of China; 4Clinical Skills Center, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 5Department of Oncology, Chongqing General Hospital, Chongqing, 401147, People’s Republic of China; 6Clinical Research Institute, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 7Clinical Medical College, Southwest Medical University, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunwei Han, The Affiliated Hospital of Southwest Medical University, 25 TAIPING Street, Luzhou City, Sichuan Province, People’s Republic of China, Tel +86-830-3165598, Email Lanpaoxiansheng@126.com Lei Han, Department of Oncology, Affiliated Hospital of Jining Medical University, Jining, 272000, People’s Republic of China, Email hanleixxf@126.comBackground: TACE and TACE with or without targeted immunotherapy are crucial comprehensive therapies for middle and advanced HCC. However, a reasonable and concise score is needed to evaluate TACE and TACE combined with systemic therapy in HCC treatment.Methods: The HCC patients were grouped into two groups: training group (n = 778) (treated with TACE) and verification group (n = 333). The predictive value of baseline variables on overall survival was analyzed using COX model, and easy-to-use ALR (AST and Lym-R) scores. The best cut-off value of AST and Lym-R were determined using X-Tile software based on total survival time (OS) and further verified via a restricted three-spline method. Meanwhile, the score was further verified using two independent valid sets: TACE combined with targeted therapy and TACE with targeted combined immunotherapy.Results: In multivariate analysis, baseline serum AST> 57.1 (p < 0.001) and Lym-R≤ 21.7 (p < 0.001) were identified as independent prognostic factors. The OS of patients in the TACE pooled cohort with 0, 1, and 2 scores were 28.1 (95% CI 24– 33.8) months, 15 (95% CI 12.4– 18.6) months, and 7.4 (95% CI 5.7– 9.1) months, respectively. The time-varying ROC curve based on ALR showed that the AUC values for predicting 1, -2-and 3-year OS were 0.698, 0.718, and 0.636, respectively. These results are confirmed in two independent valid sets of TACE combined with targeted therapy and TACE with targeted combined immunotherapy. And we established a nomogram after COX regression to predict the 1 -, 2- and 3-year survival time.Conclusion: Our study confirmed that ALR score can predict the prognosis of HCC treated with TACE or TACE combined with systemic therapy.Keywords: TACE, immunotherapy, targeted therapy, nomogram

Cong You, Zhiwei Wu, Mingyi Liao, Xiaoying Ye, Longnian Li, Tao Yang Department of Dermatology and Venereology, Candidate Branch of National Clinical Research Centre for Skin and Immune Diseases, The First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of ChinaCorrespondence: Longnian Li; Tao Yang, Department of Dermatology and Venereology, Candidate Branch of National Clinical Research Centre for Skin and Immune Diseases, The First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China, Tel +8614770833995 ; +8618720732351, Email li_longnian@foxmail.com; danny20021068@sina.comPurpose: To compare treatment duration, influencing factors, and costs among intravenous antibiotic groups combined with 2% mupirocin ointment for treating staphylococcal scalded skin syndrome (SSSS).Patients and Methods: Sex, age, onset days before admission, febrile status, white blood cell (WBC) count, and C-reactive protein (CRP) level were recorded as baseline characteristics for 253 included patients. The antibiotic sensitivity results were statistically compared by Cochran’s Q test. Kruskal–Wallis tests were used to compare days and the total costs of hospitalization with different intravenous antibiotic applications. Mann–Whitney U-tests or Spearman’s rank correlation tests were used for the univariate analysis. Finally, a multivariate linear regression model was employed to determine the variables with statistical significance.Results: The sensitivity rates of oxacillin (84.62%), vancomycin (100%), and mupirocin (100%) were significantly higher than those of clindamycin (7.69%) (p< 0.0001). The duration of intravenous ceftriaxone administration was significantly longer than that of amoxicillin-clavulanic acid, cefathiamidine, and cefuroxime (p< 0.01). The total hospitalization costs for cefathiamidine were significantly higher than those for amoxicillin-clavulanic acid and cefuroxime (p< 0.05). According to the multiple linear regression, ages ≥ 60 months old were correlated with shorter treatment duration (β=− 1.48, [95% CI: − 2.29, − 0.66] for amoxicillin-clavulanic acid, and β=− 1.44, [95% CI: − 2.06, − 0.83] for cefathiamidine, and β=− 0.96, [95% CI: − 1.58, − 0.34] for cefuroxime) (all p< 0.01). In multivariate analysis for cefathiamidine, higher WBC count (β=0.05, [95% CI: 0.01, 0.10], p< 0.05) and CRP level (β=1.12, [95% CI: 0.14, 2.10], p< 0.05) were associated with longer treatment course.Conclusion: Oxacillin resistance was rare, and clindamycin resistance was high in pediatric patients with SSSS in our district. Intravenous amoxicillin-clavulanic acid and cefuroxime combined with topical mupirocin were favorable due to a shorter intravenous treatment course and lower costs. Younger age, elevated WBC count, and CRP levels could indicate a longer course of treatment with intravenous antibiotics.Keywords: staphylococcal scalded skin syndrome, Staphylococcus aureus, amoxicillin-clavulanic acid, cephalosporins, mupirocin, intravenous antibiotic treatment course

Zijun Wu,1,2,&ast; Qin Yang,3,&ast; Kai Xu,2 Juanjuan Wu,2 Bin Yang1,2 1The First School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Burn and Plastic Surgery, General Hospital of Central Theater Command, Wuhan, People’s Republic of China; 3Department of Laboratory Medicine, General Hospital of Central Theater Command, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Yang, The First School of Clinical Medicine, Southern Medical University, Nos.1023-1063, Shatai South Road, Baiyun District, Guangzhou, Guangdong, 510515, People’s Republic of China, Tel +86-18062601971, Email sszxkyb1@163.comBackground: IL-27 involves psoriasis pathogenesis potentially by promoting excessive keratinocyte proliferation. However, the underlying mechanisms remain unclear. This study aims to explore the key genes and molecular mechanisms of IL-27-induced keratinocyte proliferation.Methods: Primary keratinocytes and immortalized human keratinocyte HaCaT cells were treated with different concentrations of IL-27 for 24 h and 48 h respectively. CCK-8 assay was used to detect cell viability and Western blot was used to detect the expression of CyclinE and CyclinB1. Primary keratinocytes and HaCaT cells were treated with IL-27, and their differentially expressed (DE) genes were obtained by transcriptome sequencing. Then Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed to predict related pathways, and the long non-coding RNA-microRNA-messenger RNA network and protein-protein interaction network were constructed to screen key genes. Biochemical experiments were performed to assess the content of glucose (Glu), lactic acid (LA), and ATP. Flow cytometry and Mito-Tracker Green staining were used to detect mitochondrial membrane potential and the number of mitochondria respectively. Western blot was performed to assess the expression of glucose transporter 1 (GLUT1), hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), phosphoglycerate kinase 1 (PGK1), phosphorylated dynamin-related protein 1 (p-DRP1) (s637) and mitofusin 2 (MFN2).Results: IL-27 concentration-dependently increased keratinocyte viability and the expression of CyclinE and CyclinB1. Bioinformatics analysis showed that the enriched pathways of DE genes were closely associated with cellular metabolism. miR-7-5p, EGFR, PRKCB, PLCB1 and CALM3 were key genes. IL-27 increased the content of LA, mitochondrial membrane potential, and the expression of GLUT1, HK2, LDHA, PGK1, p-DRP1 (s637), and MFN2, accompanied by decreased contents of Glu and ATP (P< 0.001).Conclusion: IL-27 potentially promotes keratinocyte proliferation by enhancing glycolysis, mitochondrial function, and mitochondrial fusion. The findings of this study may be conducive to revealing the role of IL-27 in the pathogenesis of psoriasis.Keywords: psoriasis, RNA-seq, glycolysis, mitochondria

Zhuchao Wu,1,&ast; Gengfeng Fu,2,&ast; Qin Wen,1,&ast; Zheyue Wang,1 Lin-en Shi,2 Beibei Qiu,1 Jianming Wang1,3,4 1Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, People’s Republic of China; 2Department of STI and HIV Control and Prevention, Center for Disease Control and Prevention of Jiangsu Province, Nanjing, 210009, People’s Republic of China; 3Department of Epidemiology, Gusu School, Nanjing Medical University, Nanjing, 211166, People’s Republic of China; 4Changzhou Medical Center, Nanjing Medical University, Nanjing, 211166, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianming Wang, Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, People’s Republic of China, Tel +86-25-86868414, Email jmwang@njmu.edu.cnPurpose: Pulmonary tuberculosis (PTB) is a severe chronic communicable disease that causes a heavy disease burden in China. Human Immunodeficiency Virus (HIV) and PTB coinfection dramatically increases the risk of death. This study analyzes the spatiotemporal dynamics of HIV, PTB and HIV-PTB coinfection in Jiangsu Province, China, and explores the impact of socioeconomic determinants.Patients and Methods: The data on all notified HIV, PTB and HIV-PTB coinfection cases were extracted from Jiangsu Provincial Center for Disease Control and Prevention. We applied the seasonal index to identify high-risk periods of the disease. Time trend, spatial autocorrelation and SaTScan were used to analyze temporal trends, hotspots and spatiotemporal clusters of diseases. The Bayesian space-time model was conducted to examine the socioeconomic determinants.Results: The case notification rate (CNR) of PTB decreased from 2011 to 2019 in Jiangsu Province, but the CNR of HIV and HIV-PTB coinfection had an upward trend. The seasonal index of PTB was the highest in March, and its hotspots were mainly distributed in the central and northern parts, such as Xuzhou, Suqian, Lianyungang and Taizhou. HIV had the highest seasonal index in July and HIV-PTB coinfection had the highest seasonal index in June, with their hotspots mainly distributed in southern Jiangsu, involving Nanjing, Suzhou, Wuxi and Changzhou. The Bayesian space-time interaction model showed that socioeconomic factor and population density were negatively correlated with the CNR of PTB, and positively associated with the CNR of HIV and HIV-PTB coinfection.Conclusion: The spatial heterogeneity and spatiotemporal clusters of PTB, HIV and HIV-PTB coinfection are exhibited obviously in Jiangsu. More comprehensive interventions should be applied to target TB in the northern part. While in southern Jiangsu, where the economic level is well-developed and the population density is high, we should strengthen the prevention and control of HIV and HIV-PTB coinfection.Keywords: pulmonary tuberculosis, HIV, spatial autocorrelation analysis, socioeconomic determinants, Bayesian space-time interaction model

Qirong Lu,1,&ast; Wantong Han,1,&ast; Defeng Wen,1,&ast; Pu Guo,1 Yu Liu,1 Zhongyuan Wu,1 Shulin Fu,1 Chun Ye,1 Xu Wang,2 Yinsheng Qiu1 1Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan, 430023, People’s Republic of China; 2National Reference Laboratory of Veterinary Drug Residues (HZAU) and Ministry of Agriculture Key Laboratory for the Detection of Veterinary Drug Residues in Foods, Huazhong Agricultural University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pu Guo; Yinsheng Qiu, Wuhan Polytechnic University, Wuhan, Hubei, 430023, People’s Republic of China, Email guopu@whpu.edu.cn; qiuyinsheng6405@whpu.edu.cnBackground: At present, the treatment and prevention of Pasteurella multocida infections in pigs mainly rely on antibiotics and vaccines, but inflammatory injury cannot be eliminated. The compound 18β-glycyrrhetinic acid (GA), a pentacyclic triterpenoid extracted from Glycyrrhiza glabra L. root (liquorice) and with a chemical structure similar to that of steroidal hormones, has become a research focus because of its anti-inflammatory, antiulcer, antimicrobial, antioxidant, immunomodulatory, hepatoprotective and neuroprotective effects, but its potential for the treatment of vascular endothelial inflammatory injury by P. multocida infections has not been evaluated. This study aimed to investigate the effects and mechanisms of GA intervention in the treatment of vascular endothelial inflammatory injury by P. multocida infections.Materials and Methods: Putative targets of GA intervention in the treatment of vascular endothelial inflammatory injury by P. multocida infections were identified using network pharmacological screening and molecular docking simulation. The cell viability of PIEC cells was investigated via the CCK-8 assay. The mechanism of GA intervention in the treatment of vascular endothelial inflammatory injury by P. multocida infections were investigated using cell transfection and western blot.Results: Through network pharmacological screening and molecular docking simulation, this study found that PARP1 may be a core target for GA to exert anti-inflammatory effects. Mechanistically, GA alleviates P. multocida-induced vascular endothelial inflammation by PARP1-mediated NF-κB and HMGB1 signalling suppression.Conclusion: These findings, for the first time, demonstrate the potential therapeutic relationship among GA, PARP1 and inflammatory injury, providing a candidate drug, therapeutic targets and explanation for treating vascular endothelial inflammatory injury caused by P. multocida infection.Keywords: network pharmacology, GA, PARP1, inflammatory injury, P. multocida infection

Zile Chen,&ast; Yiting Li,&ast; Shu Nie, Zhouwei Wu Department of Dermatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhouwei Wu, Department of Dermatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China, Email zhouwei.wu@shgh.cnPurpose: Vitiligo is an acquired depigmented skin disorder. Though genetic background, autoimmune dysregulation, and oxidative stress were reported involved in the development of vitiligo, the exact pathogenesis remains largely unknown. This study aimed to investigate potential functional proteins, pathways, and serum biomarkers involved in active vitiligo.Patients and Methods: Tandem Mass Tags (TMT) method was used to determine differentially expressed proteins (DEPs) in serum samples between 11 active vitiligo patients and 7 healthy controls of Chinese Han population.Results: A total of 31 DEPs were identified (P < 0.05, fold change > 1.2), with 21 proteins upregulated and 10 proteins downregulated in the vitiligo group. DEPs were enriched in GO terms such as “extracellular exosome” and “immunoglobulin receptor binding”, as well as KEGG pathways including “cysteine and methionine metabolism” and other immune-related pathways. Furthermore, ALDH1A1 and EEF1G achieved areas under receiver-operating characteristic (ROC) curve of 0.9221 and 0.8571, respectively. The expression levels of these 2 proteins were validated in another active vitiligo patient group.Conclusion: Our research provided novel insight into serum proteomic profile for vitiligo patients, detecting ALDH1A1 and EEF1G as potential biomarkers for active vitiligo and therapeutic intervention. Our work also detected several DEPs and associated pathways in the serum of active vitiligo patients, reinforcing the roles of retinoic acid and exosome processes in vitiligo pathogenesis.Keywords: vitiligo, active, proteomic profile, serum, biomarker