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Yuexiang Qin,1,2 Shanhu Yao,3,4 Gaoyuan Wang,5 Ziyuan Xu,6,7 Gangcai Zhu,8 Ying Li,1,2 Pingting Yang,1,2 Jiangang Wang,1,2 Chunbo Zou,5 Changhan Chen7,9 1Department of Health Management Medicine, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, 410013, People’s Republic of China; 2Hunan Chronic Disease Health Management Medical Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, 410013, People’s Republic of China; 3Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, 410013, People’s Republic of China; 4Key Laboratory of Medical Information Research, Central South University, Changsha, Hunan Province, 410013, People’s Republic of China; 5Department of Nephrology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 6Department of Otolaryngology, Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, People’s Republic of China; 7National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 8Department of Otolaryngology, Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, People’s Republic of China; 9National Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, People’s Republic of ChinaCorrespondence: Changhan Chen, National Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China, Tel +86-13875974606, Email changhanchen@csu.edu.cnObjective: Inflammation plays a crucial role in the development of metabolic syndrome (MetS). However, the roles of pepsinogens (PGs) and gastrin, known biomarkers linked to gastric inflammation, in MetS and the transition of MetS status are unclear. This research aimed to explore the relationship between MetS, the transition of MetS status, and levels of gastric biomarkers.Methods: This large-scale cross-sectional study included 19162 participants aged 18– 80 years between August 2021 and March 2024. Serum levels of the gastric biomarkers PGI, PGII, and gastrin-17 were analyzed using enzyme-linked immunosorbent assay. In addition, the relationship between transitions of MetS status based on 1032 MetS-negative participants from baseline to the second health exam after 2 years was considered. The association between MetS and the transitions of MetS status and gastric biomarkers was analyzed using logistic regression models.Results: The prevalence of MetS in the study population was 31.4%, with higher rates in males (35.2%) than females (24.6%). Gastrin-17 levels were markedly elevated in participants with MetS, a trend observed in both genders. In the logistic regression analysis, after adjusting for confounding factors, gastrin-17 levels were strongly and positively correlated with MetS in the entire cohort and in males but not in females. Male participants with MetS had lower levels of PGI and PGII than those without MetS, whereas the opposite trend was observed in females. Logistic regression analysis indicated that PGI and PGII were not independently associated with MetS. During the follow-up of 2 years, 199 (19.28%) of the 1032 MetS-negative participants transitioned to MetS-positive status. As compared to the stable MetS-negative subjects, transition from MetS-negative to MetS-positive was associated with higher levels of gastrin-17, especially in males, but not in females.Conclusion: Gastrin-17 is a promising biomarker for MetS, exhibiting potential utility in monitoring the transition of MetS status and revealing gender difference.Keywords: gastric biomarkers, gastrin-17, metabolic syndrome, transition, gender difference

Zhiying Yang,1,* Shun Yao,1,2,* Yichong Xu,1 Xiaoqing Zhang,1,2 Yuan Shi,1,2 Lijun Wang,1,2 Donghong Cui1,2 1Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Psychotic Disorders, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Donghong Cui, Email manyucc@126.comBackground: Schizophrenia is a devastating mental disease with high heritability. A growing number of susceptibility genes associated with schizophrenia, as well as their corresponding SNPs loci, have been revealed by genome-wide association studies. However, using SNPs as predictors of disease and diagnosis remains difficult. Here, we aimed to uncover susceptibility SNPs in a Chinese population and to construct a prediction model for schizophrenia.Methods: A total of 210 participants, including 70 patients with schizophrenia, 70 patients with bipolar disorder, and 70 healthy controls, were enrolled in this study. We estimated 14 SNPs using published risk loci of schizophrenia, and used these SNPs to build a model for predicting schizophrenia via comparison of genotype frequencies and regression. We evaluated the efficacy of the diagnostic model in schizophrenia and control patients using ROC curves and then used the 70 patients with bipolar disorder to evaluate the model’s differential diagnostic efficacy.Results: 5 SNPs were selected to construct the model: rs148415900, rs71428218, rs4666990, rs112222723 and rs1716180. Correlation analysis results suggested that, compared with the risk SNP of 0, the risk SNP of 3 was associated with an increased risk of schizophrenia (OR = 13.00, 95% CI: 2.35– 71.84, p = 0.003). The ROC-AUC of this prediction model for schizophrenia was 0.719 (95% CI: 0.634– 0.804), with the greatest sensitivity and specificity being 60% and 80%, respectively. The ROC-AUC of the model in distinguishing between schizophrenia and bipolar disorder was 0.591 (95% CI: 0.497– 0.686), with the greatest sensitivity and specificity being 60% and 55.7%, respectively.Conclusion: The SNP risk score prediction model had good performance in predicting schizophrenia. To the best of our knowledge, previous studies have not applied SNP-based models to differentiate between cases of schizophrenia and other mental illnesses. It could have several potential clinical applications, including shaping disease diagnosis, treatment, and outcomes.Keywords: schizophrenia, SNP, diagnostic model, bipolar disorder, differential diagnosis

Zuohu Niu,1,&ast; Jialiang Chen,2,&ast; Huijing Wang,3,&ast; Rongrui Wang,3,4 Hongye Peng,3 Shaojie Duan,5 Shukun Yao4 1Department of Infections, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Graduate School, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 5Department of Geriatrics, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaojie Duan, Department of Geriatrics, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, People’s Republic of China, Email 1782802171@qq.com Shukun Yao, Department of Gastroenterology, China-Japan Friendship Hospital, No. 2 Yinghua East Street, Chaoyang District, Beijing, 100029, People’s Republic of China, Email shukunyao@126.comPurpose: It is unclear how the Chinese Visceral Adiposity Index (cVAI) relates to metabolic dysfunction-associated fatty liver disease (MAFLD) and alanine aminotransferase (ALT) in nonobese individuals. In this study, we evaluated the ability of the cVAI to predict MAFLD and elevated ALT in nonobese participants.Methods: This cross-sectional study recruited 541 nonobese subjects from March 2019 to January 2022 with the age range of 18– 80 years. Hepatic steatosis was diagnosed by ultrasound. Participants were divided into four groups according to cVAI quartiles. To assess the associations between cVAI and MAFLD and elevated ALT, multivariate logistic regression was used. Receiver operating characteristic (ROC) curves were generated to evaluate the ability of the cVAI to predict MAFLD and elevated ALT.Results: Compared to the group with the lowest cVAI, the group with the highest cVAI was positively associated with nonobese MAFLD [16.173 (4.082– 64.073), P < 0.001] and elevated ALT [8.463 (2.859– 25.049), P < 0.001]. The area under the ROC curve (AUC) of the cVAI was greater than that of WC, waist-to-height ratio, or BMI for predicting nonobese MAFLD in the male, female, > 38 and ≤ 38 years old subgroups (P < 0.05), respectively. In addition, the ability of the cVAI to predict MAFLD was better in females, young individuals, and individuals with a higher education level (P < 0.05). The cVAI also had good predictive ability for elevated ALT levels [0.655 (0.602– 0.708)], particularly in females, young people, and highly educated participants. Furthermore, the cVAI was strongly positively correlated with the liver fibrosis score (P < 0.05) and was also a strong indicator of concomitant metabolic syndrome in nonobese MAFLD patients [AUC = 0.688 (0.612– 0.763)].Conclusion: The cVAI was strongly related to nonobese MAFLD and elevated ALT. The cVAI may be a reliable and accessible predictor of nonobese MAFLD and elevated ALT.Keywords: Chinese visceral adiposity index, metabolic dysfunction-associated fatty liver disease, nonobese, Chinese, cross-sectional study

David F Blackburn,1 Shenzhen Yao,2 Jeff G Taylor,1 Qais Alefan,3 Lisa M Lix,4 Dean T Eurich,5 Niteesh K Choudhry6 1College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; 2Public Health Surveillance Unit, Vancouver Coastal Health Authority, Vancouver Coastal Health, Vancouver, British Columbia, Canada; 3Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 4Department of Community Health Sciences, Max Rady Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; 5School of Public Health, University of Alberta, Edmonton, Alberta, Canada; 6Department of Medicine, Brigham and Women’s Hospital/Harvard Medical School, Boston, MA, USACorrespondence: David F Blackburn, Email d.blackburn@usask.caPurpose: To measure the impact of beliefs, expectations, side effects, and their combined effects on the risk for medication nonpersistence.Patients and methods: Using a cross-sectional design, individuals from Saskatchewan, Canada who started a new antihypertensive, cholesterol-lowering, or antihyperglycemic medication were surveyed about risk factors for nonpersistence including: (a) beliefs measured by a composite score of three questions asking about the threat of the condition, importance of the drug, and harm of the drug; (b) incident side effects attributed to treatment; and (c) expectations for side effects before starting treatment. Descriptive statistics and logistic regression models were used to quantify the influence of these risk factors on the outcome of nonpersistence. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated.Results: Among 3,029 respondents, 5.8% (n=177) reported nonpersistence within four months after starting the new drug. After adjustment for numerous covariates representing sociodemographics, health-care providers, medication experiences and beliefs, both negative beliefs (OR: 7.26, 95%CI: 4.98– 10.59) and incident side effects (OR: 8.00, 95%CI: 5.49– 11.68) were associated with the highest odds of nonpersistence with no evidence of interaction. In contrast, expectations for side effects before starting treatment exhibited an important interaction with incident side effects following treatment initiation. Among respondents with incident side effects (n=741, 24.5%), the risk for early nonpersistence was 11.5% if they indicated an expectation for side effects before starting the medication compared to 23.6% if they did not (adjusted OR: 0.38, 95%CI: 0.25– 0.60).Conclusion: Expectations for side effects may be a previously unrecognized but important marker of the probability to persist with treatment. A high percentage of new medication users appeared unprepared for the possibility of side effects from their new medication making them less resilient if side effects occur.Keywords: adherence, persistence, beliefs, attitudes, expectations

Dongping Wan,1,2,&ast; Shihang Cao,1,2,&ast; Xinrui Li,3,4,&ast; Qiang Zan,2 Shuxin Yao,1 Jianbing Ma,1 Lei Shang,1,3 Chao Xu1,3 1Department of Knee Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2The First Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China; 3Department of Health Statistics, Faculty of Preventive Medicine, the Air Force Military Medical University, Xi’an, People’s Republic of China; 4School of Medicine, Northwest University, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Xu; Lei Shang, Email 383697196@qq.com; fmmushanglei@163.comBackground: The High Activity Arthroplasty Score (HAAS) is a validated score that assesses functional outcomes after lower limb arthroplasty, with fewer ceiling effects than other scores. The aim is to translate and cross-culturally adapt the HAAS into a Chinese version (HAAS-C) and to evaluate the psychometric properties of HAAS-C in patients after primary total knee arthroplasty (TKA).Methods: A total of 104 patients diagnosed with knee osteoarthritis who had undergone TKA at least 12 months prior were recruited. A forward and backward translation procedure was performed for developing a culturally acceptable HAAS-C. Internal consistency was assessed using Cronbach’s α, and test-retest reliability was measured using the intraclass correlation coefficient (ICC) within a 10-day interval. Construct validity was assessed by examining the correlations between HAAS-C and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), EuroQoL Group’s five-dimension questionnaire (EQ-5D-5L), and Oxford knee score (OKS).Results: HAAS-C demonstrated adequate Internal consistency reliability, as indicated by Cronbach’s α coefficient of 0.75. Test-retest reliability yielded excellent results, with an ICC value of 0.98. Content validity indices were high, with a scale-level validity index of 0.9 and item-level validity indices greater than or equal to 0.8. HAAS-C showed a strong correlation with WOMAC (r = 0.69), a moderate correlation with EQ-5D-5L (r = 0.43), and OKS (r = 0.53) while exhibiting no floor or ceiling effects.Conclusion: The validated HAAS-C questionnaire is a valid instrument for assessing patients undergoing TKA in mainland China.Keywords: high activity arthroplasty score, total knee arthroplasty, Chinese validation, reliability, validity

Lu Liu,1 Shuang Yuan,1 Shouheng Yao,1 Wenjiao Cao,1,2 Lihua Wang1 1The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, People’s Republic of China; 2Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, 200030, People’s Republic of ChinaCorrespondence: Lihua Wang; Wenjiao Cao, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No. 910, Hengshan Road, Xuhui District, Shanghai, 200030, People’s Republic of China, Tel +86-21-18017316018, Fax +86-21-64073896, Email drwanglh0420@163.com; cwj1479@163.comPurpose: Approximately 20% of patients with type I endometrial cancer (EC) of the uterus experience recurrence and metastasis. However, existing data do not provide sufficient evidence for the utility of protein levels as prognostic biomarkers in type I EC. This study aims to determine whether epiplakin1 (EPPK1) and progesterone receptor (PR) play a role in the recurrence and metastasis of type I EC.Methods: Following the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) for assessing the quality of biomarker research results, a retrospective analysis was conducted on clinical information and tissue samples of type I EC patients. Protein expression data and clinical data for type I EC were downloaded from The Cancer Proteome Atlas (TCPA) database. We utilized the Kaplan-Meier (K-M) method and Cox proportional hazards regression analyses to evaluate whether epiplakin1 (EPPK1), progesterone receptor (PR) and certain clinical parameters can serve as independent prognostic factors. The Immune Cell Abundance Identifier (ImmuCellAI) and Cancer Immunome Atlas (TCIA) were employed to predict responses to immunotherapy. Immunohistochemistry was carried out to assess the expression of EPPK1 in type I EC.Results: Type I EC patients with high EPPK1 and low PR expression had higher International Federation of Gynecology and Obstetrics (FIGO) stage, recurrence, and metastasis rates. Furthermore, EPPK1 was identified as an independent prognostic factor, and low expression of EPPK1 was predominantly observed in the POLE ultramutated (POLEmut) group, indicating a favorable prognosis. Additionally, the high EPPK1 expression group had a lower Immune Prognostic Score (IPS), suggesting that the high-expression group may not benefit from immune checkpoint inhibitors.Conclusion: High expression of EPPK1 is an independent prognostic factor in type I EC patients with low PR expression. It can identify a subgroup of patients at high risk of recurrence. A more aggressive treatment approach is recommended for these patients.Keywords: type I endometrial cancer, progesterone receptor, epiplakin1, prognostic biomarker, immunotherapy

Saiyu Gao,1– 3 Nanqi Huang,4 Wenmin Huang,5 Yu Lian,5 Huiming Xiao,5 Shuyu Yao5 1Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Gastroenterology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 5Ocular Emergency and Trauma Department, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, People’s Republic of ChinaCorrespondence: Shuyu Yao, Email yaoshuyu@gzzoc.comIntroduction: Position adherence of patients with Pars Plana Vitrectomy with Silicone Oil Tamponade after discharge is of positive significance. However, patients undergoing a day surgery makes the quality of discharge teaching and readiness for hospital discharge is insufficient, which will influence their position adherence at home.Aim: This study aimed to find the correlation of discharge teaching, readiness for hospital discharge, and position adherence in patients who underwent PPV with silicone oil tamponade from the day ward.Methods: This was a cross-sectional survey. One hundred ninety-four patients with day surgery were recruited by convenient sampling from Zhongshan Ophthalmic Center, China. Data were collected using the quality of discharge teaching scale, readiness for hospital discharge scale, and position adherence scale.Results: Patients’ education level, residence, poor postoperative vision, ophthalmic surgery history, and quality of discharge teaching are the main factors of readiness for discharge. Only 41(21%) patients had good position adherence, and education level and readiness for discharge are the main factors of position adherence.Discussion: Discharge teaching improves patients’ knowledge and competence of self-care and helps patients prepare for the transition from hospital to home, and readiness for hospital discharge significantly influences position adherence after discharge and indirectly plays a vital role in postoperative vision recovery and surgical effect.Keywords: discharge teaching, readiness for hospital discharge, position adherence, pars plana vitrectomy with silicone oil tamponade

Miaomiao Sun,1– 3,&ast; Fuquan Wang,1– 3,&ast; Haopeng Li,1– 3 Mengyu Li,1– 3 Yu Wang,1– 3 Chenchen Wang,1– 3 Yan Zhang,1– 3 Dingyu Zhang,1– 4 Jianhua Li,5 Shanglong Yao1– 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, 430022, People’s Republic of China; 4Wuhan Jinyintan Hospital, Wuhan, 430023, People’s Republic of China; 5Department of Critical Care Medicine, Chongqing University Jiangjin Hospital, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shanglong Yao; Jianhua Li, Email yaoshanglong@hust.edu.cn; jianhuali2022@cqu.edu.cnBackground: Sepsis-associated acute kidney injury (SA-AKI) is a common complication in patients with sepsis, triggering high morbidity and mortality. Maresin-1 (MaR1) is a pro-resolution lipid mediator that promotes the resolution of acute inflammation and protects organs from inflammation.Methods: In this study, we established an SA-AKI model using cecal ligation and puncture (CLP) and investigated the effect and mechanism of MaR1. The blood and kidneys were harvested 24 hours after surgery. The blood biochemical/routine indicators, renal function, SA-AKI-related pathophysiological processes, and AMPK/SIRT3 signaling in septic mice were observed by histological staining, immunohistochemical staining, Western blot, qPCR, ELISA and TUNEL Assay.Results: MaR1 treatment alleviated kidney injury in septic mice, reflected in improved pathological changes in renal structure and renal function. MaR1 treatment decreased the levels of serum creatinine (sCr) and blood urea nitrogen (BUN) and the expressions of KIM-1, NGAL and TIMP-2, which were related to kidney injury, while inhibited the expressions of inflammatory factors TNF-α, IL-1β and IL-6. The expression of endoplasmic reticulum stress-related indicators p-PERK/PERK, GRP78, p-EIF2α/EIF2α, ATF4, CHOP, and pyroptosis-related indicators Caspase-1, NLRP3, GSDMD, IL-18, and IL-1β also decreased after MaR1 treatment. The mechanism may be related to the activation of the AMPK/SIRT3 signaling pathway, and an AMPK inhibitor (compound C) partially reverses MaR1’s protective effects in septic mice.Conclusion: Taken together, these findings suggest that MaR1 may partially ameliorate SA-AKI by activating the AMPK/SIRT3 signaling pathway, providing a potential new perspective for research on SA-AKI.Keywords: Maresin-1, pyroptosis, AMPK/SIRT3, endoplasmic reticulum stress, sepsis-associated acute kidney injury, inflammation

Jing Liu,1 Che Wang,2 Yutong Wang,2 Shukun Yao3 1China-Japan Friendship Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2School of Qi Huang, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Shukun Yao, Email shukunyao@126.comIntroduction: Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease, which is usually associated with type 2 diabetes mellitus (T2DM) and obesity. However, the incidence of MALFD in non-obese individuals without T2DM is increasing, and the pathogenesis is unclear. Serum uric acid to creatinine ratio (sUA/Cr) can reflect overall metabolic status. This study aims to observe the association between sUA/Cr and MAFLD in non-obese individuals without T2DM.Methods: A total of 21,996 individuals were included in this study. The subjects were divided into four subgroups: non-obese patients without T2DM, obese patients without T2DM, non-obese patients with T2DM, and obese patients with T2DM. Logistic regression analyzed the correlation between sUA/Cr and MAFLD subgroups. Receiver operating characteristics analyzed the predictive value of sUA/Cr for MAFLD subgroups. The stratified analyses by sex and age were performed.Results: Non-obese MAFLD individuals without T2DM had higher sUA/Cr levels than their counterparts. sUA/Cr was significantly correlated positively with MAFLD in non-obese patients. Similar results were observed in both males and females and in populations at all age stages (all p< 0.01). sUA/Cr was capable of discriminating MAFLD in non-obese individuals without T2DM (AUC: 0.667), especially for patients over 60 years old (AUC: 0.704).Conclusion: The sUA/Cr ratio was correlated with MAFLD in non-obese patients without T2DM. The predictive value of sUA/Cr for MAFLD was observed. Hence, the sUA/Cr ratio might be given more concern for the risk of MAFLD in non-obese individuals without T2DM.Keywords: uric acid, creatinine, metabolic dysfunction-associated fatty liver disease, non-obesity, type 2 diabetes mellitus

Jiamin Ma,1– 3,&ast; Fuquan Wang,1,2,&ast; Jingxu Wang,1,2,&ast; Pengcheng Wang,4 Xiaoke Dou,1,2 Shanglong Yao,1,2 Yun Lin1,2 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; 3Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 201620, People’s Republic of China; 4Department of Anesthesiology, Zhumadian Central Hospital, Zhumadian, 463000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun Lin, Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277, Jiefang Avenue, Wuhan, Hubei, 430022, People’s Republic of China, Tel/Fax +86 02785351606, Email franklinyun@hust.edu.cnPurpose: This study aims to evaluate the effects of the intraoperative application of low-dose esketamine on postoperative neurocognitive dysfunction (PND) in elderly patients undergoing general anesthesia for gastrointestinal tumors.Methods: Sixty-eight elderly patients were randomly allocated to two groups: the esketamine group (group Es) (0.25 mg/kg loading, 0.125mg/kg/h infusion) and the control group (group C) (received normal saline). The primary outcome was the incidence of delayed neurocognitive recovery (DNR). The secondary outcomes were intraoperative blood loss, the total amount of fluid given during surgery, propofol and remifentanil consumption, cardiovascular adverse events, use of vasoactive drugs, operating and anesthesia time, the number of cases of sufentanil remedial analgesia, the incidence of postoperative delirium (POD), the intraoperative hemodynamics, bispectral index (BIS) value at 0, 1, 2 h after operation and numeric rating scale (NRS) pain scores within 3 d after surgery.Results: The incidence of DNR in group Es (16.13%) was lower than in group C (38.71%) (P < 0.05). The intraoperative remifentanil dosage and the number of cases of dopamine used in group Es were lower than in group C (P < 0.05). Compared with group C, DBP was higher at 3 min after intubation, and MAP was lower at 30 min after extubation in group Es (P

Shengsheng Yao,1,&ast; Bo Zhang,2,&ast; Xiang Fei,3 Mingming Xiao,4 Li Lu,5 Daming Liu,6 Siyuan Zhang,7 Jianchun Cui3 1China Medical University - Department of Thyroid and Breast Surgery, Liaoning Provincial People’s Hospital, Shenyang, Liaoning Province, 110015, People’s Republic of China; 2Department of Science and Education, The 10th Division of Xinjiang Production and Construction Corps, Beitun General Hospital, Beitun City, Xinjiang Province, 831300, People’s Republic of China; 3Department of Thyroid and Breast Surgery, People’s Hospital of China Medical University (Liaoning Provincial People’s Hospital), Shenyang, Liaoning Province, 110015, People’s Republic of China; 4Department of Pathology, People’s Hospital of China Medical University (Liaoning Provincial People’s Hospital), Shenyang, Liaoning Province, 110015, People’s Republic of China; 5Department of Endocrinology, People’s Hospital of China Medical University (Liaoning Provincial People’s Hospital), Shenyang, Liaoning Province, 110015, People’s Republic of China; 6Department of Ultrasound, People’s Hospital of China Medical University (Liaoning Provincial People’s Hospital), Shenyang, Liaoning Province, 110015, People’s Republic of China; 7Department of Thyroid and Breast Surgery, The 10th Division of Xinjiang Production and Construction Corps, Beitun General Hospital, Beitun City, Xinjiang Province, 831300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianchun Cui, Department of Thyroid and Breast Surgery, People’s Hospital of China Medical University (Liaoning Provincial People’s Hospital), No. 33 of Wenyi Road, Shenhe District, Shenyang, Liaoning Province, 110015, People’s Republic of China, Tel +86 24 24016014, Fax +86 24 24016014, Email cjc7162003@aliyun.comAbstract: The prevalence of antibody-negative chronic autoimmune thyroiditis (SN-CAT) is increasing. The early diagnosis of SN-CAT can effectively prevent its further development. Thyroid ultrasound can diagnose autoimmune thyroiditis and predict hypothyroidism. Primary hypothyroidism with a hypoechoic pattern suggested by thyroid ultrasound and negative thyroid serum antibodies is the main basis for the diagnosis of SN-CAT. However, for early SN-CAT, only hypoechoic thyroid changes and serological antibodies are currently available. This study explored how to achieve an accurate and early diagnosis of SN-CAT and prevent the development of SN-CAT combined with hypothyroidism. The diagnosis of a hypoechoic thyroid by artificial intelligence is expected to be a breakthrough in the accurate diagnosis of SN-CAT.Keywords: antibody negative, autoimmune thyroiditis, hypothyroidism, hypoechoic thyroid, artificial intelligence, Hashimoto’s disease

Haotian Wu,1,&ast; Chunxia Li,2,&ast; Song Liu,1 Shuangquan Yao,1 Zhaohui Song,1 Dong Ren,1 Pengcheng Wang1 1Department of Orthopaedic Surgery, The 3rd Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of China; 2Department of Imaging Medicine, General Hospital of Inner Mongolia Autonomous Region, Hohhot, Inner Mongolia, 010017, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haotian Wu, Department of Orthopaedic Surgery, The 3rd Hospital, Hebei Medical University, No. 139 Ziqiang Road, Shijiazhuang, 050051, People’s Republic of China, Tel +86-311-88603682, Fax +86-311-87023626, Email surgeon_wu@126.comPurpose: Neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and red blood cell distribution width (RDW) are novel biomarkers to indicate the inflammatory/immune response, and demonstrated to be effective in diagnosis, severity evaluation, and prognosis in a variety of chronic or acute conditions. This study aims to examine whether NLR, PLR and EDW are independently associated with mortality in necrotizing fasciitis (NF).Methods: This study retrospectively enrolled patients diagnosed with NF and based on vitality status during hospitalization or within 30 days after discharge, survival and non-survival groups were defined. For distinctly comparing NLR, PLR, RDW and others, we enrolled the matched healthy controls of the same age and sex as the survivors of NF in a 1:1 ratio, which constituted the healthy control group. Comparisons were made between three groups. Variables tested with a P value < 0.10 were further entered into the multivariate logistic regression model to identify their independent association with mortality.Results: A total of 281 subjects were included, including 127 healthy controls, 127 survivors, and 27 nonsurvivors with NF, respectively, indicating a mortality rate of 17.5%. ROC analysis showed that the optimal cutoff value for NLR, PLR and RDW was 11.1, 196.0 and 15.5%, respectively, and was tested as significant only for the first two (P < 0.001, = 0.004). Multivariate logistic analysis showed that NLR ≥ 11.1 (OR, 2.51) and PLR ≥ 196.0 (OR, 2.09) were independently associated with an increased risk of mortality in NF patients, together with age ((OR, 1.28, for each 10-year increment), comorbid diabetes mellitus (OR, 2.69) and liver disease (OR, 1.86), and elevated creatinine level (OR, 1.21 for each 10 umol/L elevation).Conclusion: Elevated NLR and PLR are significant and independent predictors of mortality and can be considered for use when evaluating patients at risk of mortality.Keywords: necrotizing fasciitis, prognosis, NLR, PLR, RDW

Shunyu Yao,1,2 Suxia Wang,3,&ast; Runxi Yi,1,4,&ast; Liwei Ran,5 Cang Zhang2 1Chinese Traditional Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Dermatology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 3Laboratory of Electron Microscopy, Pathological Center, Peking University First Hospital, Beijing, People’s Republic of China; 4Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 5Department of Dermatology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liwei Ran, Department of Dermatology, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86 010 85231374, Email wlbrlw@163.com Cang Zhang, Department of Dermatology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 23 Back Street of Art Gallery, Dongcheng District, Beijing, 100010, People’s Republic of China, Tel +86 13693219292, Email zhangcang@bjzhongyi.comAbstract: An 81-year-old woman presented with purpura, petechiae, ecchymoses, flesh or brown-colored waxy, smooth, papules, warty plaque, nail dystrophy and palmodigital erythematous swelling for more than 6 years. She was diagnosed as multiple myeloma-associated systemic amyloidosis after skin subcutaneous histopathological examinations and relevant examinations such as blood and bone marrow. Systemic amyloidosis is closely related with multiple myeloma (MM). Multiple and pleomorphic skin lesions are not usual among patients with multiple myeloma or systemic amyloidosis.Keywords: multiple myeloma, primary systemic amyloidosis, monoclonal immunoglobulin

Zhiguo Zhang,1,2,&ast; Fangda Fu,1,2,&ast; Yishan Bian,1,2,&ast; Huihao Zhang,1,2 Sai Yao,1,2 Chengcong Zhou,1,2 Yuying Ge,2 Huan Luo,3 Yuying Chen,4 Weifeng Ji,1 Kun Tian,1 Ming Yue,5 Weibin Du,6 Hongting Jin,1 Peijian Tong,1 Chengliang Wu,1,2 Hongfeng Ruan1,2 1Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, People’s Republic of China; 2The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 4The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 5Department of Physiology, College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 6Research Institute of Orthopedics, The Affiliated Jiangnan Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongfeng Ruan; Chengliang Wu, Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Fax +86 571 86613684, Email rhf@zcmu.edu.cn; wcl@zcmu.edu.cnBackground: With the rapid growth of the elderly population, the incidence of osteoarthritis (OA) increases annually, which has attracted extensive attention in public health. The roles of dietary intake in controlling joint disorders are perhaps one of the most frequently posed questions by OA patients, while the information about the interaction between dietary intake and OA based on scientific research is limited. α-Chaconine is the richest glycoalkaloid in eggplants such as potatoes. Previous evidence suggests that α-Chaconine is a toxic compound to nervous and digestive systems with potentially severe and fatal consequences for humans and farm animals, but its effect on OA development remains obscure.Objective: To determine whether α-Chaconine deteriorates OA progression through sensory innervation and chondrocyte pyroptosis via regulating nuclear factor-κB (NF-κB) signaling, providing evidence for a possible linkage between α-Chaconine and OA progression.Methods: We established a mouse OA model by destabilization of medial meniscus (DMM) surgery and then intra-articular injection of 20 or 100 μM α-Chaconine into the OA mice for 8 and 12 weeks. The severity of OA progression was evaluated by histological staining and radiographic analyses. The expressions of matrix metabolic indicators, Col2, Mmp3, and Mmp13, as well as pyroptosis-related proteins, Nlrp3, Caspase-1, Gsdmd, IL-1β, IL-18, were determined by immunohistochemistry. And the changes in sensory nerve ingrowth and activity of NF-κB signaling were determined by immunofluorescence.Results: We found that α-Chaconine could exacerbate mouse OA progression, resulting in subchondral sclerosis, osteophyte formation, and higher OARSI scores. Specifically, α-Chaconine could augment cartilage matrix degradation and induce chondrocyte pyroptosis and nerve ingrowth. Mechanistical analysis revealed that α-Chaconine stimulated NF-κB signaling by promoting I-κB α phosphorylation and p65 nuclear translocation.Conclusion: Collectively, our findings raise the possibility that α-Chaconine intake can boost chondrocyte pyroptosis and nerve ingrowth to potentiate OA progression by activating NF-κB signaling.Graphical Abstract: Keywords: α-Chaconine, osteoarthritis, pyroptosis, nerve ingrowth, NF-κB signaling

Zhen Hui,1,&ast; Kelei Guo,2,&ast; Chao Liu,3 Qishuai Ma,3 Weiwei Tian,2 Shujun Yao2 1School of Marxism, Zhaoqing University, Zhaoqing, People’s Republic of China; 2School of Physical Education and Health, Zhaoqing University, Zhaoqing, People’s Republic of China; 3School of Physical Education, Huaibei Normal University, Huaibei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kelei Guo; Chao Liu, Email 2021010043@zqu.edu.cn; 827056169@qq.comPurpose: This study examined the relationship between physical exercise (PE) and prosocial behavior (PSB) and constructed a chain mediation model through the mediating effect of physical education learning motivation (PELM) and emotional intelligence (EI).Methods: Through the stratified random sampling, 1053 students (average age = 14 years, SD = 0.96 years) that complied with the requirements were surveyed from Henan Province in China. PE, EI, PELM, and PSB were assessed using standard scales. For data analysis, Pearson’s correlation analysis, structural equation model test, and bias-corrected percentile Bootstrap method were carried out in turn.Results: (1) There was a significant positive correlation between PE and PSB (r = 0.137), and the direct path between PE and PSB was significant (β = 0.09, t = 4.73, p < 0.01); (2) PE can positively predict EI (β= 0.08, t = 5.27, p < 0.01) and PELM (β= 0.04, t = 2.07, p < 0.05), EI can significantly and positively PSB (β= 0.67, t = 22.12, p < 0.01), PELM can significantly and positively predict PSB (β= 0.05, t =2.20, p< 0.05); (3) EI and physical learning motivation play a significant intermediary role between PE and PSB. The mediating effect consists of three indirect effects: PE → EI → PSB (the mediating effect value is 0.055), PE → PELM → PSB (the mediating effect value is 0.002), PE → EI → PELM → PSB (the mediating effect value is 0.002); (4) The chain mediation effect is significant in girls, but not in boys.Conclusion: (1) PE can positively predict PSB. (2) EI and PELM had significant mediating effects between PE and PSB, including single mediating effects of EI and PELM and chain mediating effects of EI-PELM; (3) There are gender differences in the chain mediation effect.Keywords: physical exercise, emotional intelligence, physical education learning motivation, prosocial behavior, junior school students, COVID-19

Yi Guan,1 Nan Liu,1 Yan Yu,1 Qiang Zhou,1,2 Meiyu Chang,1,2 Yongheng Wang,1 Sanqiao Yao1,2 1School of Public Health, North China University of Science and Technology, Tangshan, People’s Republic of China; 2School of Public Health, Xinxiang Medical University, Xinxiang, People’s Republic of ChinaCorrespondence: Sanqiao Yao, Email sanqiaoyao@xxmu.edu.cnPurpose: The objective of this study was to evaluate and compare the histopathological implications of silica nanoparticles (Nano-SiO2) and indium-tin oxide nanoparticles (Nano-ITO), in vivo.Methods: Male Sprague-Dawley rats were exposed to Nano-SiO2 (50 mg/kg) and Nano-ITO (6 mg/kg) by a single intratracheal instillation, respectively. Broncho-alveolar lavage fluid (BALF) and lung tissue were obtained at 7, 14, 28, and 56 days post exposure for analysis of BALF inflammatory factors, total protein, and for lung tissue pathology. Histopathological and ultrastructural change in lungs were investigated by hematoxylin and eosin, Masson’s trichrome, sirius red staining, periodic acid Schiff stain, and transmission electron microscopy. The expression of SP-A, collagen type I and III in lung tissue was determined by immunohistochemistry and ELISA.Results: The rats in both models exhibited obvious collagen fibrosis and the severity of the lung injury increased with time after exposure to respective dosage increased. Several parameters of pulmonary inflammation and fibrosis significantly increased in both groups, which was reflected by increased LDH activity, total proteins, TNF-α, and IL-6 levels in BALF, and confirmed by histopathological examination. The results also showed that the two models exhibited different features. Exposure to Nano-ITO caused persistent chronic lung inflammation, illustrated by the infiltration of a large amount of enlarged and foamy macrophages and neutrophils into the lung parenchyma. In Nano-SiO2 exposed rat lung tissue, granulomatous inflammation was most prominent followed by progressive and massive fibrotic nodules. Compared with the Nano-SiO2 rats, Nano-ITO exposed rats exhibited significantly severe pulmonary alveolar proteinosis (PAP) pathological changes, lower fibrosis, and higher levels of inflammatory biomarkers. However, Nano-SiO2 exposed rats had greater fibrosis pathological changes and more severe granulomas than Nano-ITO exposed rats.Conclusion: This study suggests that the Nano-SiO2-induced model has greater value in research into granulomas and fibrosis, while the Nano-ITO-induced model has greater repeatability in area of PAP.Keywords: silica nanoparticles, indium-tin oxide nanoparticles, silicosis, indium lung disease, pulmonary alveolar proteinosis

In astrophysics and space, supercritical shock is generated when an object interacts with an incoming supersonic plasma stream. Its downstream plasmas are highly turbulent, containing abundant vortices on all scales from magnetohydrodynamic to electron gyroscales. Understanding the production of these vortices is at the forefront, especially on the electron scale. Using ultrafast measurements of NASA's Magnetospheric Multiscale spacecraft, we report on the fortunate multi‐spacecraft observation of the formation of an electron vortex directly generated inside the Earth's quasi‐parallel bow shock transition and propagated to the downstream turbulent magnetosheath. The vortex is generated inside the shock transition by anisotropic ∼100–600 eV electrons trapped in an ion‐scale magnetic hole which could show a tornado‐like magnetic morphology. Our results demonstrate that the electron vortex can develop not only as a product of the forward cascade but also from the shock transition into its downstream turbulence, which adds to the short‐scale turbulence and dissipation. Plain Language Summary: Turbulence is a ubiquitous process in fluids where nonlinear interactions take place to generate dynamically evolving vortex structures across a broad range of scales. It plays a leading role in the cascade of mass and energy transport to increasingly small scales until it is dissipated as heat. In ionized plasmas, turbulence is more complex when considering electromagnetic fields, different kinds of charged particles, waves, and dissipation mechanisms. For studying plasma turbulence, a readily available natural laboratory is the near‐Earth environment. The solar wind plasma encounters the Earth's magnetosphere, generating a supercritical bow shock. The plasma downstream of the bow shock is highly turbulent and contains abundant plasma vortices from the macroscale to the electron gyroscale. Therefore, understanding the bow shock's role in vortex generation is crucial and essential to understanding the development of turbulence in collisionless magnetized plasmas. This paper presents a precise origin of electron‐scale vortex for unpredictable and random plasma turbulence. The vortex can directly start inside the collisionless shock as a small‐scale vortex before being transported downstream turbulence, instead of the popular belief that developing from the downstream turbulence and larger‐scale vortices. Key Points: Electron vortex can directly start inside the supercritical shock as a small‐scale vortex before being transported downstream turbulenceEvidence for its generation inside the shock transition is provided by identifying the energetic shock electron population as its sourceThe vortex could show a tornado‐like magnetic morphology, coupling with a magnetic hole and propagating to the downstream magnetosheath [ABSTRACT FROM AUTHOR]

Nan Liu,1 Yi Guan,1 Chunling Zhou,2 Yongheng Wang,1 Zhanfei Ma,3 Sanqiao Yao1,4 1School of Public Health, North China University of Science and Technology, Tangshan, 063210, Hebei, People’s Republic of China; 2Baoding Center for Disease Control and Prevention, Baoding, 071030, Hebei, People’s Republic of China; 3Institute of Industrial Hygiene of Ordnance Industry, Xian, 710065, Shanxi, People’s Republic of China; 4XinXiang Medical University, Xinxiang, 453003, Henan, People’s Republic of ChinaCorrespondence: Sanqiao Yao, North China University of Science and Technology, Bohai Avenue 21, Tangshan, 063210, Hebei, People’s Republic of China, Fax +86-315-8805583, Email sanqiaoyao@xxmu.edu.cnPurpose: The main objective of this study was to clarify the biodistribution and in vivo toxicological effects of indium-tin oxide nanoparticles (Nano-ITO) in male rats.Methods: Dose-response (three divided doses) and time-course studies (six exposure durations) were performed to examine Nano‑ITO-induced pulmonary and systemic toxicity. At the end of the experiment, hematology and serum biochemical parameters were determined, and cytokines levels and oxidative stress were analyzed in the bronchoalveolar lavage fluid. In addition, indium biodistribution following Nano‑ITO exposure was determined using inductively coupled plasma mass spectrometer to measure indium concentration in the lung, spleen, brain, liver, kidney, and testis. Rat lung tissues were also harvested for staining with hematoxylin and eosin, periodic acid Schiff stain, Masson’s trichrome, and Sirius red.Results: Relative lung weights were significantly increased in all Nano-ITO-exposed groups. All organs exhibited a statistically significant difference in indium levels. Rat exposure to Nano‑ITO resulted in a dose-response increase in acute systemic inflammation and injury. BALF analysis revealed significantly elevated levels of lung oxidative stress, pulmonary injury, and inflammatory markers across most groups. Serum biochemistry results showed that Nano-ITO could affect the liver and renal functions of rats when exposed for 3 days. Compared with the control group, significant inflammatory responses or pathological changes were observed in the liver, kidney, and testis of rats at different sampling times and three doses examined. Histopathologically, foci of slight-to-severe pulmonary inflammatory response along with acute inflammatory, pulmonary fibrosis and alveolar proteinosis were detected, and the severity of these lesions worsened in a dose- and time-dependent manner.Discussion: These findings provide novel evidence that enhanced progressive massive pulmonary fibrosis, diffuse interstitial fibrosis, and collagen accumulation play a role in the development of pulmonary alveolar proteinosis following Nano-ITO exposure.Keywords: indium-tin oxide nanoparticles, pulmonary fibrosis, pulmonary alveolar proteinosis

Shenzhen Yao,1 Lisa Lix,2 Gary Teare,3 Charity Evans,1 David Blackburn1 1College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; 2Department of Community Health Sciences of Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; 3Program Program Knowledge, Evidence and Innovation, Provincial Population and Public Health, Alberta Health Services, Calgary, Alberta, CanadaCorrespondence: David BlackburnCollege of Pharmacy and Nutrition, University of Saskatchewan, 2A20.01 Health Sciences Building, 107 Wiggins Road, Saskatoon, Saskatchewan, S7N5E5, CanadaTel +1 306 966 2081Fax +1 306 966 6377Email d.blackburn@usask.caPurpose: Age or sex concordance (same sex or same age range) may also be associated with medication adherence but was not fully investigated. We aim to quantify the impact of age and sex concordance on optimal adherence to statin medications.Patients and Methods: A retrospective cohort study was conducted using population-based health administrative data from Saskatchewan, Canada. Participants were individuals newly initiated on statin medications between January 1, 2012, and December 31, 2017. The outcome was optimal adherence (proportion of days covered ≥ 80%) measured at one year after the first statin claim. The independent variables were sex and age concordance (age within five years) between patients and prescribers. The association between adherence outcome and sex/age concordance was analyzed by multivariable logistic regression models using generalized estimating equations controlled by a package of potential confounding factors.Results: Among 51,874 new statin users, 20.6% (n = 10,710) were age concordant with prescriber. The vast majority of age concordance occurred in patients younger than 66 years (88.6%, 9,486/10,710). Sex concordance was observed in 62.8% (n = 32,551) of patients and age-sex combined concordance in 13.2% (n = 6,856). Among patients younger than 66 years (n = 36,641/51,874, 70.6%), age concordance did not have a significant impact on optimal adherence [adjusted OR (aOR) = 1.02, 95% CI 0.97 to 1.07]. Weak association between sex concordance (aOR = 1.05, 95% CI 1.00 to 1.11), and age-sex combined concordance (aOR = 1.05, 95% CI 0.99 to 1.12) was observed.Conclusion: Age and sex concordance were not statistically significant predictors of optimal statin adherence. However, a weak association was detected for sex concordance. Future studies should examine this factor in different health care settings.Keywords: medication adherence, age concordance, sex concordance, statin, observational study, cohort

Reliable, robust, and inexpensive disinfection systems are needed to expand water security in remote and underserviced areas. This paper reports on the deployment and evaluation of a novel UV water-disinfection system in a remote rural community. Prior laboratory tests indicated a 7.12 log10 reduction of the bacteriophage MS-2 at a flow rate of 9.46 liter/min, which corresponds to a supplied UV dose 215 mJ/cm2. Further tests in water containing turbidity levels up to 18 NTU showed E. coli removal remaining above the 5 log10 level. Field testing was performed at a Native American reservation in Northern California where the system was used to treat groundwater obtained from a well with a known fecal contamination. The system was powered by solar panel and was operated on-demand for extended periods. Tests on the treated water showed that the system exceeded the standard of disinfection required for drinking water.

Huihao Zhang,1,&ast; Sai Yao,1,&ast; Zhiguo Zhang,1,&ast; Chengcong Zhou,1 Fangda Fu,1 Yishan Bian,1 Huan Luo,2 Yan Li,1 Shuxin Yan,1 Yuying Ge,1 Yuying Chen,3 Kunyu Zhan,4 Yanzhi Ge,1 Zuxiang Chen,1 Ming Yue,5 Xiaofeng Li,6 Weibin Du,1,7 Hongting Jin,1 Peijian Tong,1 Hongfeng Ruan,1,8 Chengliang Wu1 1Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 5Department of Physiology, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 6Department of Orthopedics and Traumatology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 7Research Institute of Orthopedics, The Affiliated JiangNan Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 8Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongfeng Ruan; Peijian TongInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaEmail rhf@zcmu.edu.cn; peijiantongzjtcm@163.comPurpose: To explore the pharmacological mechanisms of Liuwei Dihuang Decoction (LWDHD) against intervertebral disc (IVD) degeneration (IVDD) via network pharmacology analysis combined with experimental validation.Methods: First, active ingredients and related targets of LWDHD, as well as related genes of IVDD, were collected from public databases. The protein–protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed to predict the core targets and pathways of LWDHD against IVDD. Secondly, the IVDD model of mice treated with LWDHD was selected to validate the major targets predicted by network pharmacology.Results: By searching the intersection of the active ingredient targets and IVDD targets, a total of 110 targets matched the related targets of 30 active ingredients in LWDHD and IVDD were retrieved. PPI network analysis indicated that 17 targets, including Caspase-3, IL-1β, P53, etc., were hub targets. GO and KEGG enrichment analyses showed that the apoptosis pathway was enriched by multiple targets and served as the target for in vivo experimental study validation. The results of animal experiments revealed that LWDHD administration not only restored the decrease in disc height and abnormal degradation of matrix metabolism in IVDD mice but also reversed the high expression of Bax, Caspase-3, IL-1β, P53, and low expression of Bcl-2, thereby inhibiting the apoptosis of IVD tissue and ameliorating the progression of IVDD.Conclusion: Using a comprehensive network pharmacology approach, our findings predicted the active ingredients and potential targets of LWDHD intervention for IVDD, and some major target proteins involved in the predictive signaling pathway were validated experimentally, which gave us a new understanding of the pharmacological mechanism of LWDHD in treating IVDD at the comprehensive level.Keywords: intervertebral disc degeneration, Liuwei Dihuang decoction, network pharmacology, pharmacological mechanisms, apoptosis

Zheng Yan,1 Shuna Yao,1 Yuanyuan Wang,2 Yanyan Liu,1 Zhihua Yao1 1Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Zhihua Yao; Yanyan LiuDepartment of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, No. 127 Dongming Road, Zhengzhou, Henan, 450008, People’s Republic of ChinaTel/Fax +86 371-65587791Email zlyyyaozhihua1260@zzu.edu.cn; yyliu@zzu.edu.cnAbstract: Primary testicular lymphoma (PTL) is a rare malignancy of testis. Although the multimodality treatment (including orchiectomy, systemic chemotherapy, scrotal radiotherapy, and preventive central nervous system (CNS)-targeted treatment) is widely used to treat PTL, recurrence, especially CNS recurrence, occurred frequently. Patients with relapsed PTL have a dismal prognosis and limited treatment options. In this report, we described the case of a 63-year-old man with early-stage PTL. The patient received the multimodality treatment, but CNS relapse occurred 3 months following the front-line therapy. We gave him a combined chemo-free regimen treatment, including rituximab, ibrutinib, and lenalidomide (RIL), based on the tumor’s gene mutation profile and the patient’s preference. A complete response was achieved after the first cycle of treatment. Whole-brain radiotherapy was delivered as consolidative treatment following three more cycles of RIL. Thereafter, ibrutinib and lenalidomide continued as maintenance treatment. As of the submission of this manuscript, the response has lasted for more than 16 months. Based on the case, we believe chemo-free regimen RIL might be a favorable approach for PTL patients with CNS relapse, especially those frail elderly patients, when alternative treatments are not available.Keywords: primary testicular lymphoma, chemo-free regimen, central nervous system relapse, case report