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Qiong Li,1 Cancan Zou,1 Linli Xie,1 Suzhen Ran,2 Yanlin Chen,1 Tianjing Yan1 1Department of Pathology, Women and Children’s Hospital of Chongqing Medical University, Chongqing Health Center for Women and Children, Chongqing, People’s Republic of China; 2Department of Ultrasound, Women and Children’s Hospital of Chongqing Medical University, Chongqing Health Center for Women and Children, Chongqing, People’s Republic of ChinaCorrespondence: Tianjing Yan; Yanlin Chen, Email 64672420@qq.com; chenyl_doctor@163.comIntroduction: The coexistence of a complete hydatidiform mole with twin live fetuses in a triplet pregnancy is an extremely rare condition with an unknown incidence.Case Report: This report presents a case of a dichorionic diamniotic triplet pregnancy complicated by the coexistence of a complete hydatidiform mole and twin live fetuses. The pregnancy resulted in a preterm delivery at 30 weeks and 5 days of gestation, with both live fetuses surviving to date. During the pregnancy, the patient was diagnosed with pre-eclampsia and intrahepatic cholestasis. Post-delivery, she was found to have an invasive mole with lung metastases, which was ultimately successfully treated.Conclusion: This report highlights critical considerations for managing a multiple pregnancy complicated by a complete hydatidiform mole, alongside the associated potential complications. In light of the limited literature on the clinical management of this condition, our findings offer valuable insights into navigating the risks and optimizing patient outcomes.Keywords: hydatidiform mole, triplet pregnancy, live fetuses

Deying Xiao,1,2,* Long Xie,1,* Wenhong Lin,1 Jinhua Fu,1 Lin Deng,1 Qian Zhuang,2,3 Maobai Liu2,3 1Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, People’s Republic of China; 2The School of Pharmacy, Fujian Medical University, Fuzhou, 350004, People’s Republic of China; 3Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Maobai Liu; Qian Zhuang, Department of Pharmacy, Fujian Medical University Union Hospital, No. 29, Xinquan Road, Antai Street, Gulou District, Fuzhou, 350001, People’s Republic of China, Tel +86-591-83357896, Email liumaobai10@163.com; ZhuangQ0591@163.comBackground: This evaluation aims to provide a reference for clinical decision-making regarding the use of SPN in intensive care unit (ICU) patients. The objective of this study is to evaluate the quality of clinical practice guidelines for the use of supplementary parenteral nutrition (SPN) in ICU patients, both domestically and internationally.Patients and Methods: The quality of clinical practice recommendations for SPN use in ICU patients was assessed using a systematic approach.Results: Five nutrition recommendations in total were included for analysis. The average standardized scores for the recommendations across the six domains of the Appraisal of Guidelines for Research and Evaluation II (AGREE II) are as follows: Scope and purpose scored 87.96%, stakeholder Involvement scored 68.52%, rigour of development scored 73.40%, clarity of presentation scored 84.80%, applicability scored 64.72%, and editorial independence scored 91.10%. In the comprehensive evaluation, two guidelines were rated as grade A recommendations, and three were rated as grade B recommendations. Most guidelines recommended against early use of SPN when energy and protein requirements could not be met solely through enteral nutrition (EN) in ICU patients. The guidelines emphasized achieving target energy levels and discontinuing parenteral nutrition (PN) as soon as the energy requirements were met to prevent overfeeding.Conclusion: This study utilized the AGREE II scale to assess the quality of five nutrition guidelines. All 5 guidelines were deemed acceptable Recommendations include focusing on participants, rigour, and applicability to enhance guideline quality. Clinicians should exercise professional judgment when applying guidelines as they complement training and judgment, rather than replacing them.Keywords: ICU, patients, supplementary parenteral nutrition, clinical practice guidelines, guideline evaluation

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

Lantian Xie,1,&ast; Yan Chen,1,&ast; Lifan Zhang,1– 3 Lidan Zhao,4 Tao Li,5 Xiaochun Shi,1,2 Xiaoqing Liu1– 3 1Division of Infectious Diseases, Department of Internal Medicine, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Clinical Epidemiology Unit, Peking Union Medical College, International Clinical Epidemiology Network, Beijing, People’s Republic of China; 4Department of Rheumatology and Clinical Immunology, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Psychological Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaochun Shi; Xiaoqing Liu, Email shixch7722@163.com; liuxq@pumch.cnObjective: Tuberculosis preventive treatment (TPT) is an important strategy for tuberculosis (TB) control. Rheumatic diseases (RD) patients are at high risk for active TB development. More researches are needed in terms of patient compliance in clinical practice. This study aims to explore the potential difficulties and obstacles in latent tuberculosis infection (LTBI) screening and TPT in RD patients.Methods: Convenience sampling was used to recruit RD outpatients who had indications for LTBI screening and TPT. All participants were given questionnaires on knowledge and attitudes regarding screening and preventive treatment of LTBI.Results: Of the 200 RD patients, most people were aware that they were at increased risk of ATB due to their rheumatic disease and knew that TB was curable. The main association with willingness to have screening for LTBI was tertiary education (P = 0.013). The main association with willingness to take treatment for LTBI was a sense of personal risk and belief that the treatment would reduce risk of ATB (P < 0.001). More than half of the people surveyed could not accept taking 6 or more pills per day, while more than half of the patients could tolerate a treatment course of 9 months or longer. Most (65.4%) preferred their own rheumatologists to initiate treatment.Conclusion: Educating RD patients about their individual risks of TB and the side effects of treatment, and educating/empowering rheumatologists to discuss these aspects with their patients and to offer LTBI screening and treatment, may help improve patients′ compliance with LTBI screening and TPT.Keywords: rheumatic diseases, latent tuberculosis infection, tuberculosis preventive treatment, knowledge, attitudes

Sheng Long,1 Peijuan Tang,1 Pengwen Ouyang,1 Xiangjian Liao,2 Liangyi Xie1 1Department of Clinical Laboratory, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, People’s Republic of China; 2Department of Clinical Laboratory, Changsha Hospital of Traditional Chinese Medicine (Changsha Eighth Hospital), Changsha, Hunan, People’s Republic of ChinaCorrespondence: Liangyi Xie, Department of Clinical Laboratory, Hunan Province People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, People’s Republic of China, Email lyxie78@hunnu.edu.cnAbstract: This case report describes the case of a female infant hospitalized for severe pneumonia. During the treatment process, various antibiotics are used to treat and prevent further infection. The child had a weak physical condition, combined with neuroblastoma, paraneoplastic syndrome, and low immune function, leading to Tsukamurella tyrosinosolvens infection. The treatment was eventually abandoned owing to poor prognosis. This study aims to through the medium, dyeing, electron microscope observation, 16s rRNA and high-throughput sequencing investigated the morphological characteristics, staining properties, electron microscope morphology, antibiotic resistance, and genomic characteristics of Tsukamurella tyrosinosolvens. The aim of the study is to provide data reference for clinical laboratory staff in bacteria identification research, and to provide relevant help for clinicians in diagnosis and treatment.Keywords: Tsukamurella tyrosinosolvens, opportunistic pathogen, MALDI-TOF MS, 16S rRNA, genomics, infant, infectious diseases

Nan Tang,1 Mengyue Pei,2 Huihui Liu,3 Jingru Chen,1 Youting Wang,1 Lei Xie,4 Junping Hu,3,5 Jing Wang,6 Yuan Gao1 1Department of Nursing, 1st Medical Centre of PLA General Hospital, Beijing, People’s Republic of China; 2School of Medicine, Henan Kaifeng College of Science Technology and Communication, Kaifei, Henan Province, People’s Republic of China; 3School of Nursing, Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China; 4Renji Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 5Department of Reproductive Medicine, The First Hospital of Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China; 6Department of Gynecology, 1th Medical Centre of PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jing Wang; Yuan Gao, Email wangjing353535@163.com; gaoyuanzd@163.comBackground: The purpose of this study was to explore the relationship between infertility-related stress and dyadic coping with quality of life (QoL) in couples with infertility issues, and verify gender differences and dyadic interactions in the associations between them.Methods: This cross-sectional study included 340 couples who were recruited from the First Affiliated Hospital of Lanzhou University between March 2022 and November 2022. The Fertility Problem Inventory, Dyadic Coping Inventory and FertiQoL were used to measure infertility-related stress, dyadic coping and QoL. The Actor-Partner Interdependence Model was used to analyze the effects of infertility-related stress and dyadic coping on the couple’s own QoL (actor effect) as well as on their partner’s QoL (partner effect).Results: Female patients perceived significantly lower levels of QoL and dyadic coping than those of husbands. There was no statistically significant difference in the infertility-related stress between wives and husbands. Husbands’ infertility-related stress had actor and partner effects on their own and their wives’ QoL, while wives’ infertility-related stress only had an actor effect on their own QoL. Husbands’ dyadic coping had both actor effect and partner effects on their own and their wives’ QoL, meanwhile wives’ dyadic coping had both actor effect and partner effects on their own and their husbands’ QoL.Conclusion: Husbands’ QoL was impacted by their own infertility-related stress, dyadic coping and their wives’ dyadic coping. Whereas wives’ QoL was influenced by infertility-related stress and dyadic coping from both their own and their spouses. Therefore, elevating the level of dyadic coping may contribute to improving QoL for both husbands and wives. Moreover, enhancing the ability to cope with infertility-related stress might be useful for husbands and indirectly contribute to wives’ QoL.Keywords: infertility, couple, infertility-related stress, dyadic coping, QoL

Fanqi Wang,1,2,&ast; Limin Xie,1,2,&ast; Yuan Tang,1,2 Tuo Deng3 1National Clinical Research Center for Metabolic Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Key Laboratory of Diabetes Immunology, Ministry of Education, and Metabolic Syndrome Research Center, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 3Clinical Immunology Center, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tuo Deng, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People’s Republic of China, Tel +8613755063233, Email dengtuo@csu.edu.cnPurpose: To clarify the significance of mitochondria-related differentially expressed genes (MTDEGs) in UC carcinogenesis through a bioinformatics analysis and provide potential therapeutic targets for patients with UC associated colorectal cancer.Methods: Microarray GSE37283 was utilized to investigate differentially expressed genes (DEGs) in UC and UC with neoplasia (UCN). MTDEGs were identified by intersecting DEGs with human mitochondrial genes. Utilizing LASSO and random forest analyses, we identified three crucial genes. Subsequently, using ROC curve to investigate the predictive ability of three key genes. Following, three key genes were confirmed in AOM/DSS mice model by Real-time PCR. Finally, single-sample gene set enrichment analysis (ssGSEA) was employed to explore the correlation between the hub genes and immune cells infiltration in UC carcinogenesis.Results: The three identified hub MTDEGs (HMGCS2, MAVS, RDH13) may exhibit significant diagnostic specificity in the transition from UC to UCN. Real-time PCR assay further confirmed that the expressions of HMGCS2 and RDH13 were significantly downregulated in UCN mice than that in UC mice. ssGSEA analysis revealed the hub genes were highly associated with CD56dim natural killer cells.Conclusion: RDH13, HMGCS2, and MAVS may become diagnostic indicators and potential biomarkers for UCN. Our research has the potential to enhance our understanding of the mechanisms underlying carcinogenesis in UC.Keywords: ulcerative colitis, colorectal cancer, autoimmunity diseases, mitochondria, NKT cells

Lianru Zhang,1,2,&ast; Jie Xiao,1,2,&ast; Yishan Li,1,2,&ast; Baorui Liu,1,2 Li Xie1,2 1The Comprehensive Cancer Center of Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 2Clinical Cancer Institute of Nanjing University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Xie; Baorui Liu, The Comprehensive Cancer Center of Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, 210008, People’s Republic of China, Email xieli@njglyy.com; baoruiliu@nju.edu.cnPurpose: As one of the most important breakthroughs in cancer therapy, immune checkpoint inhibitors have greatly prolonged survival of patients with breast cancer. However, their application and efficacy are limited, especially for advanced HER2-negative breast cancer. It has been reported that epigenetic modulation of the histone deacetylase (HDAC) inhibitor chidamide, as well as immune microenvironment modulation of radiotherapy are potentially synergistic with immunotherapy. Thus, the combination of chidamide, radiotherapy and immunotherapy is expected to improve prognosis of patients with advanced HER2-negative breast cancer.Patients and Methods: This is a single-arm, open, prospective clinical trial investigating the efficacy and safety of the combination of HDAC inhibitor chidamide, anti-PD-1 antibody sintilimab, and the novel immuno-radiotherapy, which aims to enhance efficacy of immunotherapy, in subsequent lines of therapy of HER2-negative breast cancer. Our study will include 35 patients with advanced breast cancer that has failed endocrine therapy and first-line chemotherapy. Participants will receive 30 mg of chidamide twice a week, 200 mg of sintilimab once every 3 weeks, combined with immuno-radiotherapy. Radiotherapy will be centrally 8 Gy for at least one lesion, and at least 1 Gy for the other lesions. We will complete three fractions of radiotherapy in one cycle. The primary endpoint is progression-free survival, and secondary endpoints are objective response rate, disease control rate and safety. Moreover, biomarkers including cytokines and lymphocyte subgroups will be explored.Conclusion: As a single-arm clinical trial, the analysis of the influence of each single treatment is limited. Besides, our study is an open study, which involves neither randomization nor blinding. In spite of the abovementioned limitations, this prospective clinical trial will give an insight into subsequent lines of therapy of HER2-negative advanced breast cancer, prolong the survival or achieve long remission for these participants, and identify potential responders.Keywords: HDAC inhibitor, sintilimab, radiation, HER2-negative breast cancer

Ying Wang, Huan Ren, Meng Li, Ling Xie, Lin Lin, Yan-Le Fang Department of Anorectal Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of ChinaCorrespondence: Ying Wang, Department of Anorectal Surgery, The Second Hospital of Hebei Medical University, 215 Heping West Road, Shijiazhuang, Hebei, 050000, People’s Republic of China, Tel +86-031166002901, Email Wangying_0628@yeah.netObjective: This study aimed to analyse the impact of enterostomal therapist-led visual health education combined with peer education on the postoperative self-nursing ability, quality of life and peristomial complications in patients with a permanent colostomy.Methods: Patients with a permanent colostomy admitted to Second Hospital of Hebei Medical University between March 2021 and March 2023 were selected and divided into the study group (60 patients) and the control group (60 patients). Enterostomal therapist-led visual health education combined with peer education was adopted in the study group, and regular education was adopted in the control group. The clinical effects between the two groups were compared.Results: Repeated measurement analysis of variance showed that the two educational methods had different effects on the quality of life (Ftreatment = 342.734, p < 0.001), self-nursing ability (Ftreatment = 256.321, p < 0.001), adaptability (Ftreatment = 321.734, p < 0.001) of patients with a permanent colostomy. After the 3-month intervention, the differences in all aspects of the quality of life, self-nursing ability and adaptability between the two groups were statistically significant, and the score of the study group was higher than that of the control group (p < 0.05). Compared with the control group, the study group had a lower incidence of the five complications (p < 0.05) and higher nursing satisfaction (Z = − 2.968, p < 0.05).Conclusion: Enterostomal therapist-led visual health education combined with peer education can improve the quality of life of patients with a permanent colostomy, improve their positive mood, reduce their negative mood, improve their adaptability to the stoma, reduce complications and improve their daily living conditions. In the future, the clinical application of visual health education and peer education in patients with permanent colostomy should be increased.Keywords: peer education, visual education, self-nursing ability, quality of life, peristomial complications, permanent colostomy patients

Boyang Dong,1,&ast; Bingquan Li,1,&ast; Liangzhen Xie,2 Yan Li2 1Graduate School, Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of China; 2Ear-Nose-Throat Department, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Li, Email liyan888111@163.comAbstract: Allergic rhinitis is a prevalent allergic diseases and has a profound impact on physical well-being. In recent years, more and more people have changed to allergic diseases, such as allergic rhinitis, allergic asthma, allergic dermatitis and so on. In the incidence of allergic rhinitis, covering all ages. The common clinical treatment of allergic rhinitis are drugs and immunotherapy, but these therapies have certain limitations. Therefore, an effective and economical treatment for AR is urgently needed. Acupuncture are widely used in the clinical treatment of various diseases, but the effect of acupuncture in the treatment of allergic rhinitis (AR) is significant, and the mechanism of acupuncture in the treatment of AR is also a hot spot. Acupuncture is one of the traditional treatment methods of traditional Chinese medicine, which achieves therapeutic effect by pressing a needle or other means at a specific location on the skin to produce a special sensation. Among them, acupuncture, as a popular treatment method, has attracted more and more attention. In this review, we provide an overview of the current understanding of acupuncture and AR, as well as current studies investigating the efficacy and safety of acupuncture for AR.Keywords: acupuncture, allergic rhinitis, pathophysiological, traditional Chinese medicine

Shiqiong Yan,1 Wenzhuo Fan,2 Yonghong Ma,3 Sijia Xie,4 Rong Li,5 Yao Lan,1 Linli Xie,5 Jie Jing5 1College of Nursing, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Nursing, Chengdu Women and Children’s Central Hospital, Chengdu, Sichuan Province, People’s Republic of China; 3State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 4School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, People’s Republic of China; 5Department of Nursing, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, People’s Republic of ChinaCorrespondence: Jie Jing, Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610072, People’s Republic of China, Tel +028-87393247, Email jingjie_1130@163.comBackground: The problem of maternal mental health is a priority issue of global concern. Dyadic coping refers to the co-managing and making decisions between two parties in response to a joint stressful event. At present, china has limited focus on dyadic coping for pregnant women during pregnancy. This study aimed to investigate different categories and characteristics of dyadic coping in pregnant women throughout pregnancy and to analyze the factors that influence these categories.Methods: This study was a cross-sectional, and 376 pregnant women who visited the obstetric clinic at a tertiary hospital in Sichuan province from June to September 2023 were interviewed face-to-face using convenience sampling. Data were collected using a sociodemographic questionnaire, dyadic coping scale, and family adaptability and cohesion evaluation scale. The data were imported into excel and exported to spss 27.0 to analyze the potential characteristics of pregnant women’s dyadic coping during pregnancy and to explore the effects of this using univariate analysis and multifactorial logistic regression.Results: A total of 376 valid questionnaires were collected. The results of the potential profile analysis showed that the dyadic coping of pregnant women during pregnancy could be categorized into three different groups: the “low coping group” (21.3%), the “general coping group” (67.5%), and the “high coping group” (11.2%). Multiple logistic regression analyses revealed that low monthly family income, early pregnancy, primipara, family adaptability and cohesion were the factors influencing the dyadic coping of pregnant women during pregnancy.Conclusion: During pregnancy, pregnant women exhibit moderate levels of dyadic coping. Three different categories of dyadic coping patterns were exhibited: low coping group, general coping group, and high coping group, with significant heterogeneity. Therefore, there is a need to focus on the dyadic coping status of various categories of pregnant women and implement targeted couple and family-wide interventions.Keywords: pregnancy period, pregnant women, dyadic coping, family adaptability and cohesion, latent profile analysis

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

Congyang Xue,1 Xiaopei Lu,2 Guangda Sun,1 Nan Wang,1 Gansheng He,1 Wenqiang Xu,1 Zhipeng Xi,1 Lin Xie1 1Department of Spine Surgery, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Department of Traditional Chinese Medicine Surgery, Nanjing Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of ChinaCorrespondence: Lin Xie, Department of Spine Surgery, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100th. Shizi Street, Nanjing, Jiangsu Province, 210028, People’s Republic of China, Email xielin@njucm.edu.cnPurpose: To explore the validity of the thoracic spine Hounsfield Unit (HU) measured by chest computed tomography (CT) for opportunistic screening of diabetic osteoporosis. The current study attempted to establish a diagnostic threshold for thoracic spine HU in a type 2 diabetes mellitus (T2DM) population with osteoporosis.Patients and Methods: The current study retrospectively included 334 patients with T2DM. They underwent chest CT and Dual-energy X-ray (DXA) between August 2021 and January 2022 in our hospital. HU values were measured on the resulting chest CT images at thoracic spine 11 and 12 to construct regions of interest. All patients were grouped according to the lowest T-value of DXA examination: osteoporosis, osteopenia and normal bone density. HU values were compared with T-values in each group of patients, and receiver operating characteristics curves were plotted to calculate diagnostic thresholds as well as sensitivity and specificity.Results: There was a strong correlation between the HU values of chest CT and the T-values of DXA (p < 0.01). The sensitivity for osteoporosis was 88.7% for T11 attenuation≤ 98 HU and the specificity for osteoporosis was 87.5% for T12 attenuation ≤ 117HU; the specificity for normal BMD was 85.4% for T11 attenuation ≥ 147 HU and 82% for T12 attenuation ≥ 146 HU.Conclusion: Chest CT can be used to screen patients with T2DM for opportunistic osteoporosis and help determine if they need DXA screening. The current study suggests that when the HU threshold of T11 ≤ 98/T12 ≤ 117, patients may need further osteoporosis screening.Keywords: osteoporosis, T2DM, HU, thoracic vertebra, chest CT

Menglu Dong,1 Xili Liang,1 Tian Zhu,1 Ting Xu,1 Liwei Xie,2,3 Yuan Feng1,4,5 1Sleep Medicine Center, Department of Psychiatric, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, People’s Republic of China; 3Department of Endocrinology and Metabolism, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 4Institute of Brain Disease, Nanfang Hospital of Southern Medical University, Guangzhou, People’s Republic of China; 5Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Science, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Liwei Xie, Email xielw@gdim.cn; Yuan Feng, Sleep Medicine Center, Department of Psychiatric, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Baiyun District, Guangzhou, 510515, People’s Republic of China, Email yuanstar@126.comBackground: Obstructive sleep apnea (OSA) is a prevalent sleep breathing disorder characterized by intermittent hypoxia (IH), with continuous positive airway pressure (CPAP) as its standard treatment. However, the effects of intermittent hypoxia/reoxygenation (IH/R) on weight regulation in obesity and its underlying mechanism remain unclear. Gut microbiota has gained attention for its strong association with various diseases. This study aims to explore the combined influence of IH and obesity on gut microbiota and to investigate the impact of reoxygenation on IH-induced alterations.Methods: Diet-induced obese (DIO) rats were created by 8-week high-fat diet (HFD) feeding and randomly assigned into three groups (n=15 per group): normoxia (NM), IH (6% O2, 30 cycles/h, 8 h/day, 4 weeks), or hypoxia/reoxygenation (HR, 2-week IH followed by 2-week reoxygenation) management. After modeling and exposure, body weight and biochemical indicators were measured, and fecal samples were collected for 16S rRNA sequencing.Results: DIO rats in the IH group showed increased weight gain (p=0.0016) and elevated systemic inflammation, including IL-6 (p=0.0070) and leptin (p=0.0004). Moreover, IH rats exhibited greater microbial diversity (p< 0.0167), and significant alterations in the microbial structure (p=0.014), notably the order Clostridiales, accompanied by an upregulation of bile acid metabolism predicted pathway (p=0.0043). Reoxygenation not only improved IH-exacerbated obesity, systemic inflammation, leptin resistance, and sympathetic activation, but also showed the potential to restore IH-induced microbial alterations. Elevated leptin levels were associated with Ruminococcaceae (p=0.0008) and Clostridiales (p=0.0019), while body weight was linked to Blautia producta (p=0.0377). Additionally, the abundance of Lactobacillus was negatively correlated with leptin levels (p=0.0006) and weight (p=0.0339).Conclusion: IH leads to gut dysbiosis and metabolic disorders, while reoxygenation therapy demonstrates a potentially protective effect by restoring gut homeostasis and mitigating inflammation. It highlights the potential benefits of CPAP in reducing metabolic risk among obese patients with OSA.Keywords: intermittent hypoxia, reoxygenation, high-fat diet-induced obese, gut microbiota, 16S rRNA

Ruiwei Guo,1,2 Jin Wu,1,2 Yanmin Zheng,1,2 Xiaona Lin,1,2 Zelin Zhuang,1,2 Jingjing Yin,1,2 Zhirong Lin,1 Lei Xie,1,2 Shuhua Ma1,2 1Department of Radiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of China; 2Laboratory of Medical Molecular Imaging, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of ChinaCorrespondence: Shuhua Ma; Lei Xie, Email shuhua6633@163.com; 13lxie1@stu.edu.cnBackground: Inflammatory Bowel Disease (IBD) patients may experience cognitive impairments in Visuospatial Working Memory (VSWM), significantly impacting their quality of life. However, the mechanisms underlying these impairments remain poorly understood.Methods: We studied functional MRI and graph theory analysis to investigate changes in functional connectivity networks during the Mental Rotation Task (MRT) in IBD patients. Twenty IBD patients (13 males, 7 females; mean age = 34.95 ± 13.80 years; mean disease duration = 2.43 ± 2.37 years) participated in the study. Exclusion criteria encompassed recent use of analgesics, 5-Aminosalicylate, corticosteroids, or immunosuppressants within the past three months. Additionally, we recruited 20 age-, gender-, and education-matched healthy controls for comparison.Results: Compared to a control group, IBD patients exhibited significantly longer reaction times and reduced accuracy during the MRT. Our analysis revealed abnormalities in multiple nodal attributes within the functional connectivity network, particularly in regions such as the bilateral orbitofrontal cortex, right supplementary motor area, bilateral parahippocampal gyrus, and bilateral anterior temporal lobe. We observed that the nodal efficiency in the left temporal pole is negatively correlated with Red Blood Cell Distribution Width (RDW) and positively correlated with response time of MRT.Conclusion: Our findings revealed notable abnormalities in multiple node attributes among IBD patients during MRT, providing evidence of cognitive impairments in VSWM in IBD patients. This study found RDW maybe can serve as a clinical indicator for predicting early VSWM impairment in patients with IBD.Keywords: inflammatory bowel disease, graph theory, visuospatial working memory, cognitive impairment, mental rotation task

Li Xie,1,&ast; Xiangyi Kong,1,2,&ast; Jidong Gao1,2 1Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, People’s Republic of China; 2Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jidong Gao, Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, People’s Republic of China, Email ab168@cicams.ac.cnAbstract: In the vast expanse of restorative surgical procedures, the Deep Inferior Epigastric Perforator (DIEP) flap, originating from the inferior epigastric artery, has emerged as the preferred method of breast reconstruction, attributable to its myriad advantages. The technique provides reliable vascular supply, robust tissue volume for excision, minimal invasiveness to the donor site, with direct closure and concealment of the said site. This paper embarks on an elaborate elucidation of the DIEP surgical procedure, pivoting on the analytical exploration of a particular instance where necrosis of the skin flap occurred following immediate DIEP breast reconstruction in a patient diagnosed with early-stage breast cancer. This patient had previously undergone Nipple Areola Complex Sparing Mastectomy (NSM). We endeavor to extrapolate insights from this singular case of post-NSM DIEP breast reconstruction failure and correlate our findings with current literature dedicated to similar instances of surgical failure in DIEP breast reconstruction.Keywords: breast cancer, NSM, DIEP, breast reconstruction

Ye Liu,1,&ast; Lifan Zhang,1– 4,&ast; Yan Chen,1,&ast; Guiren Ruan,1– 3 Yuchen Liu,1 Shi Chen,1 Lantian Xie,1 Fengying Wu,1 Xiaochun Shi,1– 3 Xiaoqing Liu1– 4 1Division of Infectious Diseases, Department of Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 3Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Clinical Epidemiology Unit, Peking Union Medical College, International Clinical Epidemiology Network, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaochun Shi; Xiaoqing Liu, Division of Infectious Diseases, Department of Internal Medicine, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan No. 1, Beijing, 100005, People’s Republic of China, Email shixch7722@163.com; liuxq@pumch.cnBackground: The population with latent tuberculosis infection (LTBI) represents a potential pool of patients with active tuberculosis (ATB). T-SPOT.TB is an important test tool for screening LTBI. Owing to the large population of LTBI patients in China, it is necessary to identify a high-risk group for LTBI and enlarge tuberculosis preventive treatment (TPT) to reduce the incidence of ATB.Methods: Hospitalized patients with positive T-SPOT.TB results were recruited from January 2013 to December 2016. Patients with ATB were excluded. Basic information was collected and the development of ATBs was examined during follow-up. The life-table method was used to calculate cumulative incidence rates. Potential risk factors were analyzed through Cox regression analysis.Results: A total of 1680 patients with LTBI were recruited in the follow-up cohort, and 377 (22.44%) patients dropped out. With a median follow-up time of 81 months [interquartile range (IQR):61– 93], 19 of 1303 patients with LTBI developed ATB. The 1-year incidence of ATB was 614 per 100,000 individuals [95%confidence interval (95% CI):584– 644]. Over 5-year period, the cumulative incidence of ATB was 1496 per 100,000 [95% CI:1430– 1570], and the incidence density was 240 per 100,000 person-years[95% CI:144– 375]. In the Cox regression model, exposure of pulmonary tuberculosis (PTB) [adjusted hazard ratio (aHR)=10.557, 95% CI:2.273– 49.031], maximum daily dosage of glucocorticoids (GCs)≥ 50 mg/d (aHR=2.948, 95% CI:1.122– 7.748), leflunomide (LEF) treatment (aHR=8.572, 95% CI:2.222 − 33.070), anemia (aHR=2.565, 95% CI:1.015– 6.479) and T-SPOT.TB level≥ 300SFCs/106 PBMCs (aHR=4.195, 95% CI:1.365– 12.892) were independent risk factors for ATB development in LTBI patients.Conclusion: The incidence of ATB is significantly higher in hospitalized patients with LTBI than in the general population. The exposure history of PTB, maximum daily dosage of GCs≥ 50 mg/day, LEF treatment, anemia, and T-SPOT.TB level≥ 300SFCs/106PBMCs, were the risk factors of tuberculosis reactivation. Hospitalized LTBI patients with the above factors may need TPT.Keywords: latent tuberculosis infection, active tuberculosis, incidence, risk factors

Pengwen Ouyang,1 Zhijie Zhou,2 Chanyuan Pan,3 Peijuan Tang,1 Sheng Long,1 Xiangjian Liao,1 Qiong Liu,1 Liangyi Xie1 1Department of Clinical Laboratory, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, People’s Republic of China; 2Department of Respiratory Medicine, The Affiliated Zhuzhou Hospital of Xiangya School of Medicine, Central South University, Zhuzhou, People’s Republic of China; 3Department of Respiratory Medicine, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, People’s Republic of ChinaCorrespondence: Liangyi Xie, Email lyxie78@hunnu.edu.cnPurpose: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is closely related to respiratory tract infection. The aim of this study was to investigate the clinical features and prognostic factors of CRKP-induced pneumonia in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients.Methods: A single-centre, retrospective case-control study on COPD patients hospitalized for acute exacerbation and CRKP-induced pneumonia was conducted from January 1, 2016, to December 31, 2022. The mortality rate of acute exacerbation due to CRKP-induced pneumonia was investigated. The patients were divided into the CRKP-induced pneumonic acute exacerbation (CRKPpAE) group and the non-CRKP-induced pneumonic acute exacerbation (non-CRKPpAE) group, and the clinical characteristics and prognostic factors were compared using univariate analysis and multivariate analysis.Results: A total of 65 AECOPD patients were included, composed of 26 patients with CRKPpAE and 39 patients with non-CRKPpAE. The mortality rate of CRKPpAE was 57.69%, while non-CRKPpAE was 7.69%. Compared with non-CRKPpAE, a history of acute exacerbation in the last year (OR=8.860, 95% CI: 1.360– 57.722, p=0.023), ICU admission (OR=11.736, 95% CI: 2.112– 65.207, p=0.005), higher NLR levels (OR=1.187, 95% CI: 1.037– 1.359, p=0.013) and higher D-dimer levels (OR=1.385, 95% CI: 1.006– 1.905, p=0.046) were independently related with CRKPpAE. CRKP isolates were all MDR strains (26/26, 100%), and MDR strains were also observed in non-CRKP isolates (5/39, 12.82%).Conclusion: Compared with non-CRKPpAE, CRKPpAE affects the COPD patient’s condition more seriously and significantly increases the risk of death.Keywords: chronic obstructive pulmonary disease, acute exacerbation, carbapenem-resistant K. pneumoniae, pneumonia

Abstract Background To explore the trajectory of, and factors contributing to, achievement of individual criteria of minimal disease activity (MDA) in patients with active psoriatic arthritis (PsA) treated with guselkumab. Methods The Phase 3, randomized, placebo-controlled DISCOVER-2 study enrolled adults (N = 739) with active PsA despite standard therapies who were biologic/Janus kinase inhibitor-naive. Patients were randomized 1:1:1 to guselkumab 100 mg every 4 weeks; guselkumab 100 mg at week 0, week 4, then every 8 weeks; or placebo. In this post hoc analysis, patients randomized to guselkumab were included and pooled (N = 493). Longitudinal trajectories of achieving each MDA criterion through week 100 were derived using non-responder imputation. Time to achieve each criterion was estimated with Kaplan-Meier analysis. Multivariate regression for time to achieve each criterion (Cox regression) and achievement at week 100 (logistic regression) was used to identify contributing factors. Results Continuous improvement across all MDA domains was shown over time. ~70% of patients achieved near remission in swollen joint count (SJC), Psoriasis Area and Severity Index (PASI), and enthesitis through week 100. Median times to achieve individual criteria differed significantly (p

Zhu Qin,1 Liangzhen Xie,1,2 Wentao Li,2 Chao Wang,1 Yan Li2 1Department of Otolaryngology, Graduate School of Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang, People’s Republic of China; 2Department of Otolaryngology, First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang, People’s Republic of ChinaCorrespondence: Yan Li; Liangzhen Xie, No. 26 Heping Road, Harbin, People’s Republic of China, Email hljzyyliyan343@163.com; xieliangzhen@hljucm.netAbstract: Allergy rhinitis (AR) is becoming more common and has serious medical and societal consequences. Sneezing, paroxysmal nasal blockage, nasal itching, mucosal edema, coughing, and rhinorrhea are symptoms of this type I allergic immunological illness. Immunoglobulin E-mediated inflammation is the cause of it. Because AR is prone to recurrent attacks, extended medication therapy may impair its effectiveness. In addition to negatively affecting the patients’ physical health, this can also negatively impact their mental health. During AR development, there are inflammatory and oxidative stress responses that are linked to problems in a number of signal transduction pathways. By using the terms “allergic rhinitis”, “traditional Chinese medicine”, “inflammation”, and “oxidative stress”, we screened for pertinent research published over the previous five years in databases like PubMed. We saw that NF-KB, TLR, IL-33/ST2, PI3K/AKT, MAPK, and Nrf2 are some of the most important inflammatory and oxidative stress pathways in AR. Studies have revealed that antioxidant and anti-inflammatory therapy reduced the risk of AR and was therapeutic; however, the impact of the therapy varies widely. The Chinese medical system places a high value on traditional Chinese medicine (TCM), which has been there for virtually all of China’s 5000-year history. By influencing signaling pathways related to inflammation and oxidative stress, Chinese herbal medicine and its constituent compounds have been shown to prevent allergic rhinitis. This review will focus on this evidence and provide references for clinical treatment and scientific research applications.Keywords: allergic rhinitis, traditional Chinese medicine, inflammatory, oxidative stress, signaling pathways

Huili Tang, Xueqing Wu, Jiamei Feng, Qingqian Gao, Shijun Shao, Wenchao Qu, Lu Xie, Jiaye Sun Department of Breast, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of ChinaCorrespondence: Xueqing Wu, Department of Breast, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 185 Pu ‘an Road, Huangpu District, Shanghai, People’s Republic of China, Tel + 86-13817792022, Fax + 86-200021, Email snow_zi@hotmail.comPurpose: To determine the risk factors, clinical characteristics, and prognosis of adolescent non-puerperal mastitis patients.Patients and methods: A retrospective analysis was conducted on 10 cases of NPM in adolescents who underwent surgical treatment at Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine from August 2021 to August 2023. We analyze the patient’s general information, clinical characteristics, related medical history, laboratory indicators, breast magnetic resonance imaging examination, postoperative pathology, prognosis, etc.Results: The clinical manifestations of NPM in adolescents mainly included redness, swelling and pain in the breasts, congenital nipple retraction, and extensive lesion range. Inflammatory markers and prolactin were elevated. Magnetic resonance imaging showed circular enhancement with abscess formation as the main type. All patients underwent surgical treatment with a fast recovery time after surgery. No recurrence was observed during follow-up and the postoperative breast appearance was satisfactory. Multivariate Logistic regression analysis indicated that congenital nipple retraction, elevated prolactin levels and trauma were independent risk factors for adolescents non-puerperal mastitis.Conclusion: Adolescent non-puerperal mastitis is a rare and unique type. Summarizing its main risk factors, clinical characteristics, and prognosis provides a basis for further research.Keywords: adolescents, non-puerperal mastitis, risk factors, clinical characteristics, prognosis

Fang Yang,1,&ast; Cong Li,2,&ast; Yuling Qiu,1 Xinjie Chen,3 Kelin Zheng,4 Donglin Kang,5 Yin Zhang,2 Baorui Liu,1 Yongzhong Yao,2 Li Xie1 1The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, People’s Republic of China; 2Department of Breast Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 3The Comprehensive Cancer Center, China Pharmaceutical University Nanjing Drum Tower Hospital, Nanjing, People’s Republic of China; 4Department of the Comprehensive Cancer Center, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 5Department of the Comprehensive Cancer Center, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Xie, The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, People’s Republic of China, Email xieli@njglyy.com Yongzhong Yao, Department of Breast Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China, Tel/Fax +86-025-83106666, Email yyz1006@hotmail.comPurpose: The coronavirus disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has delayed medical consultations, especially for patients receiving intravenous anti-cancer therapy. We aim to investigate alterations in immune function among breast cancer patients who experience delayed intravenous therapy due to SARS-CoV-2 infection.Patients and Methods: We performed an observational investigation of breast cancer patients in Nanjing Drum Tower Hospital from December 27, 2022, to January 20, 2023. Patients who recovered from SARS-CoV-2 infection were eligible for enrollment. Peripheral blood samples were taken prior to the restart of intravenous anti-cancer therapy to examine hematologic parameters.Results: A total of 131 patients were included in the final analysis. Cough (74.0%), fever (62.6%), and expectoration (46.6%) were identified as the most presenting symptoms of SARS-CoV-2 infection in breast cancer. The average nucleic acid conversion time and delayed treatment time was 13.4 days and 13.9 days, respectively. The patients > 60 years old experienced prolonged nucleic acid conversion time (P = 0.017) and delayed treatment time (P = 0.028) compared to those

Nan Tang,1,2,&ast; Mengyue Pei,2,3,&ast; Lei Xie,2,4 Xueping Liang,2 Junping Hu,2,5 Yuan Gao1 1Department of Nursing, 1th Medical Centre of PLA General Hospital, Beijing, People’s Republic of China; 2School of Nursing, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 3Henan Kaifeng College of Science Technology and Communication, Kaifei, Henan, People’s Republic of China; 4Renji Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 5The First hospital of Lanzhou University, Lanzhou, Gansu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junping Hu; Yuan Gao, Email hjplandashengzhi@126.com; gaoyuanzd@163.comBackground: This study aims to examine the relationship between anxiety and depression and dyadic coping in infertile couples, exploring gender differences and dyadic interactions in these associations.Methods: A cross-sectional study was conducted involving 288 couples recruited from the First Affiliated Hospital of Lanzhou University between November 2021 and November 2022. The Dyadic Coping Scale, Anxiety Scale, and Depression Scale were utilized to measure dyadic coping, anxiety, and depression, respectively. The Actor-Partner Interdependence Model was used to analyze the actor effect and partner effect.Results: Wives exhibited significantly higher anxiety and depression scores compared to husbands (p< 0.001). No statistically significant difference was found in dyadic coping between wives and husbands. Positive dyadic coping in infertile couples had significant actor effects on anxiety and depression (p< 0.05) and partner effects (p< 0.05). Positive dyadic coping negatively predicted anxiety and depression of oneself and one’s partner. Negative dyadic coping in infertile couples also had significant actor effects on anxiety and depression (p< 0.05) and partner effects (p< 0.05). Negative dyadic coping positively predicted anxiety and depression of oneself and one’s partner.Conclusion: The dyadic coping style of infertile couples has both actor and partner effects on their own and their partner’s anxiety and depression. Anxiety and depression in infertile couples are influenced by their own and their partner’s dyadic coping style, respectively. Therefore, dyadic coping serves as an important indicator for predicting psychological outcomes in these couples.Keywords: infertility couple, dyadic coping, anxiety, depression

Zhiwei Chen,1,&ast; Chuling Zhu,2,&ast; Lingna Huang,1,&ast; Yuanjie Qi,1 Xiaoyao Guo,1 Li Xie,1 Hua Li1 1Department of Gynecologic, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Women’s health Department, QuanZhou Women and Children’s Hospital, Quanzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Li, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian, 350001, People’s Republic of China, Tel +86-18005016206, Email fjsfylihua@163.com Li Xie, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian, 350001, People’s Republic of China, Tel +86-13635281861, Email 309381162@qq.comObjective: Excessive pain will have adverse effects on the mother and fetus. Labor epidural analgesia greatly reduces the pain, which is widely carried out abroad. Labor epidural anesthesia-associated fever (LEAF) is the biggest problem for labor epidural anesthesia. This study aimed to evaluate the clinical value of serum magnesium levels to predict the LEAF.Methods: Overall 528 singleton term-pregnant women who underwent labor epidural anesthesia in Fujian Provincial Maternity and Children’s Health Hospital, affiliated hospital of Fujian Medical University from January 2019 to June 2019, were analyzed retrospectively. The serum magnesium level was detected using venous blood samples. The relationship between the serum magnesium level and LEAF was interpreted, and the optimal cut-off values of the serum magnesium level to predict LEAF were calculated.Results: Overall, 65 (12.30%) participants had LEAF. And a higher rate of the bulging membrane, gestational hypertension, neonatal intensive care unit (NICU) admission, and the different mode of delivery was significantly associated with LEAF. Also, the serum magnesium level demonstrated higher significantly in presence of LEAF than absence (P< 0.05). What is more, it indicated that the area under the receiver operating characteristic curve (AUC) for the serum magnesium level was 0.825, and an optimal cut-off of the serum magnesium level was 0.855 mg/dl. Furthermore, it demonstrated that the serum magnesium level had the highest OR (OR= 7.49; 95% CI (4.58– 14.35)) (P< 0.001). The bulging membrane is an independent risk factor presence of LEAF (OR = 1.55; 95% CI (1.01– 2.43)) (P=0.038).Conclusion: This study demonstrated that the baseline of serum magnesium can provide a suitable biomarker to predict LEAF. It can help to provide a useful target for LEAF treatment and enhance surveillance before fever.Keywords: serum magnesium level, labor epidural anesthesia associated fever, inflammation, risk, therapy

Abstract Introduction Guselkumab previously showed greater improvements versus placebo in axial symptoms in patients with psoriatic arthritis (PsA) (assessed by Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] and Ankylosing Spondylitis Disease Activity Score [ASDAS]), in post hoc analyses of the phase 3, placebo-controlled, randomized DISCOVER-1 and DISCOVER-2 studies. We now evaluate durability of response in axial-related outcomes through 2 years of DISCOVER-2. Methods DISCOVER-2 biologic-naive adults with active PsA (≥ 5 tender/ ≥ 5 swollen joints, C-reactive protein ≥ 0.6 mg/dl) were randomized to guselkumab 100 mg every 4 weeks (Q4W) or at week 0, week 4, then Q8W, or placebo → guselkumab Q4W at week 24. Among patients with imaging-confirmed sacroiliitis (investigator-identified), axial symptoms were assessed through 2 years utilizing BASDAI, BASDAI Question #2 (spinal pain), modified BASDAI (mBASDAI; excludes Question #3 [peripheral joint pain]), and ASDAS. Mean changes in scores and proportions of patients achieving ≥ 50% improvement in BASDAI (BASDAI 50) and ASDAS responses, including major improvement (decrease ≥ 2.0), were determined through week 100. Treatment failure rules (through week 24) and nonresponder imputation of missing data (post-week 24) were utilized. Mean BASDAI component scores were assessed through week 100 (observed data). Exploratory analyses evaluated efficacy by sex and HLA-B*27 status. Results Among 246 patients with PsA and imaging-confirmed sacroiliitis, guselkumab-treated patients had greater mean improvements in BASDAI, mBASDAI, spinal pain, and ASDAS scores, lower mean BASDAI component scores, and greater response rates in achieving BASDAI 50 and ASDAS major improvement vs. placebo at week 24. Differences from placebo were observed for guselkumab-treated patients in selected endpoints regardless of sex or HLA-B*27 status. At week 100, mean improvements were ~ 3 points for all BASDAI scores and 1.6–1.7 for ASDAS; 49–54% achieved BASDAI 50 and 39% achieved ASDAS major improvement at week 100. Conclusions Guselkumab treatment provided durable and meaningful improvements in axial symptoms and disease activity in substantial proportions of patients with active PsA and imaging-confirmed sacroiliitis. Trial Registration Clinicaltrials.gov NCT03158285.

Objective To evaluate gene expression in blood of patients with psoriatic arthritis (PsA) versus healthy controls and identify changes associated with guselkumab treatment. Methods Whole blood transcriptome profiling via paired‐end RNA sequencing was conducted using samples from DISCOVER‐1 and DISCOVER‐2 at baseline (n = 673) and at weeks 4 and 24 from a representative subgroup that received placebo or guselkumab (n = 227 [longitudinal PsA cohort]). Baseline samples were compared with demographically matched healthy controls (n = 21). Guselkumab‐mediated changes in gene expression were assessed in participants from the longitudinal PsA cohort who did versus did not achieve at least 20% improvement in American College of Rheumatology response criteria (ACR20) or at least 75% improvement in Psoriasis Area and Severity Index (PASI75). Differential gene expression was analyzed using edgeR. Results At baseline, 355 upregulated and 314 downregulated genes (PsA‐associated genes) were identified in patients with PsA versus healthy controls. Upregulated genes were related to neutrophil, mononuclear cell, and CD11b+ gene sets. No cell type–specific gene sets were identified among downregulated genes. Most PsA‐associated genes were modulated by guselkumab treatment. At week 24, genes downregulated by guselkumab were enriched with neutrophil, monocyte, eosinophil, and macrophage gene sets; genes upregulated by guselkumab were enriched with B cell, T cell, and natural killer cell gene sets. Reductions in expression of upregulated PsA‐associated gene sets were more pronounced in ACR20 and PASI75 responders than in nonresponders. Conclusion These findings suggest a dysregulation of immune cell profiles in blood from patients in the baseline PsA cohort that approached levels in healthy controls after guselkumab treatment.

Su-Fei Pan,&ast; Shi-Mei Huang,&ast; Lian Xie, Yuan-Yuan Zhang, Yu-Rong Tang, Xiao-Zhen Wang Department of Clinical Laboratory, Shengli Oilfield Central Hospital, Dongying, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Zhen Wang, Department of Clinical Laboratory, Shengli Oilfield Central Hospital, No. 31 Jinan Road, Dongying District, Dongying, Shandong, 257034, People’s Republic of China, Tel +86-18654610519, Email xiaozhenwang007@163.comAbstract: Scedosporium apiospermum (S. apiospermum) is typically reported to be involved in superficial and subcutaneous fungal infections but overlooked in invasive infections, which is associated with a high mortality rate. It poses a diagnostic challenge due to its confusable characteristics to other hyaline hyphomycetes. Here, we reported a psoriasis patient with an invasive S. apiospermum infection. The patient presents an abscess at the intermuscular space of the left hip and an increased C-reactive protein level. Pus culture showed white-greyish, cottonlike colonies with aerial mycelium and terminal oval conidia, suggesting S. apiospermum. This rare fungus was rapidly confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and RNA sequencing. The patient was successfully treated with voriconazole with no recurrence of the abscesses despite delayed treatment. This is the first such case infection report from China that described an unusual case of intermuscular space abscesses due to S. apiospermum. This report highlights the possibility of fungal infections in deeper tissue, as well as the necessity of thorough evaluation and microbiological diagnosis for invasive infections, particularly in immunocompromised patients.Keywords: fungi, fungal infections, infectious diseases, Scedosporium, abscesses, voriconazole

Ruoshan Wu,1 Longjun Jing,1,2 Yang Liu,3 Huilin Wang,3,4 Lin Xie,5 Wu Deng6 1School of Physical Education, Hunan University of Science and Technology, Xiangtan, 411201, People’s Republic of China; 2China Athletics College, Beijing Sport University, Beijing, 100084, People’s Republic of China; 3School of Business, Hunan University of Science and Technology, Xiangtan, 411201, People’s Republic of China; 4Faculty of Economics, Chulalongkorn University, Bangkok, 10330, Thailand; 5School of Physical Fitness of Guangzhou Sport University, Guangzhou, 510000, People’s Republic of China; 6School of Physical Education, Shenzhen University, Shenzhen, 518000, People’s Republic of ChinaCorrespondence: Huilin Wang, Email 15897325733@163.comPurpose: Despite the Advances in sports training methods and medicine, they have not reduced the recurrence rate of athletes’ injuries significantly, and obligatory exercise may be an important reason for their re-injury. The purpose of this study was to investigate the effects of mindfulness on obligatory exercise behavior, self-criticism, and competitive state anxiety in athletes recovering from injury, and explain their interactions.Patients and Methods: The study adopted the snowball and convenience sampling methods. From November to December 2022, a total of 265 high-level sports players in South China were selected, and ultimately, 208 valid data samples were obtained. Maximum likelihood estimation was used to analyze the data and test the hypotheses proposed using 5000 bootstrap samples to test the mediating effects of the structural equation model.Results: The results demonstrated that there were positive correlations between self-criticism and obligatory exercise (standardized coefficients = 0.38, p < 0.001), as well as competitive state anxiety and self-criticism (standardized coefficients = 0.45, p < 0.001). Mindfulness and obligatory exercise were correlated negatively (standardized coefficients = − 0.31, p < 0.001), but there was no significant relation between competitive state anxiety and obligatory exercise (standardized coefficients = 0.05, p > 0.01). Self-criticism and competitive state anxiety mediated mindfulness’s positive effects on obligatory exercise in part (standardized indirect effect = − 0.16, p < 0.01), and this explanatory power was higher than in any previous study (R2 = 0.37).Conclusion: The irrational beliefs in Activating events–Beliefs–Consequence (ABC) theory play an important role in explaining athletes’ obligatory exercise, and mindfulness has a positive effect on reducing obligatory exercise behavior.Keywords: obligatory exercise, mindfulness, cognitive behavioral therapy, ABC theory, sports reinjury

Objective Evaluate long-term guselkumab effectiveness across Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-recognised domains/related conditions of psoriatic arthritis (PsA).Methods Post hoc analyses used data from DISCOVER-2 (NCT03158285) biologic/Janus-kinase inhibitor-naïve participants with active PsA (≥5 swollen/≥5 tender joints, C-reactive protein ≥0.6 mg/dL), randomised (1:1:1) to guselkumab every 4 or 8 weeks (Q4W/Q8W) or placebo with crossover to guselkumab. Outcomes aligned with key GRAPPA-recognised domains of overall disease activity, peripheral arthritis, axial disease, enthesitis/dactylitis and skin psoriasis (nail psoriasis was not evaluated). PsA-related conditions (inflammatory bowel disease (IBD)/uveitis) were assessed via adverse events through W112. Least squares mean changes from baseline through W100 in continuous outcomes employed repeated measures mixed-effects models adjusting for baseline scores. Binary measure response rates were determined with non-responder imputation for missing data.Results 442/493 (90%) of guselkumab-randomised patients completed treatment through W100. Following early reductions in disease activity with guselkumab, durable improvements were observed across key PsA domains (swollen/tender joints, psoriasis, spinal pain, enthesitis/dactylitis) through W100. Response rates of therapeutically relevant targets generally increased through W100 with guselkumab Q4W/Q8W: Disease Activity Index for PsA low disease activity (LDA) 62%/59%, enthesitis resolution 61%/70%, dactylitis resolution 72%/83%, 100% improvement in Psoriasis Area and Severity Index 59%/53%, Psoriatic Arthritis Disease Activity Score LDA 51%/49% and minimal disease activity 38%/40%. Through W112, no cases of IBD developed among guselkumab-randomised patients and one case of uveitis was reported.Conclusion In biologic-naïve patients with active PsA, guselkumab provided early and durable improvements in key GRAPPA-recognised domains through 2 years, with substantial proportions achieving important treatment targets.

Objective Previous analyses of pooled DISCOVER‐1 and DISCOVER‐2 data through Week 24 showed significantly higher rates of dactylitis resolution in patients treated with guselkumab compared with placebo. Here, we investigate associations between dactylitis resolution and other outcomes through 1 year. Methods Patients were randomized 1:1:1 to receive subcutaneous injections of guselkumab 100 mg at Week 0, Week 4, and then every 4 or 8 weeks, or placebo with crossover to guselkumab at Week 24. Independent assessors determined dactylitis severity score (DSS; 0‐3/digit; total = 0‐60). Dactylitis resolution (DSS = 0) (prespecified) and at least 20%, at least 50%, and at least 70% DSS improvement from baseline (post hoc) were determined through Week 52 (nonresponder imputation for treatment failure through Week 24 and for missing data through Week 52). ACR50, tender/swollen joints, low disease activity (LDA) as assessed by composite indices, and radiographic progression (DISCOVER‐2 only) were assessed in patients with dactylitis versus without dactylitis resolution at Week 24 and Week 52. Results Patients with dactylitis at baseline (473 of 1118) had more severe joint and skin disease than those without dactylitis (645 of 1118). At Week 52, approximately 75% of guselkumab‐randomized patients with dactylitis at baseline had complete resolution; approximately 80% had at least 70% DSS improvement. Through Week 52, new‐onset dactylitis (DSS ≥1) was uncommon among patients with a DSS of 0 at baseline. Guselkumab‐randomized patients with dactylitis resolution were more likely to achieve ACR50, at least 50% reduction in tender and swollen joints, and LDA at Week 24 and Week 52 than those without resolution. At Week 52, patients with dactylitis resolution had numerically less radiographic progression from baseline (DISCOVER‐2). Conclusion Through 1 year, approximately 75% of guselkumab‐randomized patients had complete resolution of dactylitis; patients exhibiting resolution were more likely to achieve other important clinical outcomes. Given the high burden of dactylitis, resolution may be associated with better long‐term patient outcomes.

Yan-Hua Luo,1 Li Xie,2 Jiao-Yang Li,3 Yuan Xie,4 Man-Qin Li,1 Li Zhou1 1Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China; 2Pediatric Medical Center, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China; 3Department of Preventive Medicine, School of Public Health, Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 4Department of Radiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of ChinaCorrespondence: Li Zhou, Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China, Tel +86 18573477875, Email zl_zhou2016@163.comPurpose: The increasing prevalence of obesity in children and its associated risk with cardiovascular diseases demand more discovery of the novel biomarkers for developing new treatment options for this complex disease. This study aimed to investigate the association of serum MOTS-C (a peptide encoded in the mitochondrial genome) levels and vascular endothelial function in obese children.Patients and Methods: A total of 225 obese children (aged 8.1 ± 2.6 years) and 218 healthy children (aged 7.9 ± 2.2 years) were enrolled. Related anthropometric assessment and biochemical evaluation were done in all subjects. Reactive hyperemia index (RHI), as assessed by the peripheral arterial tonometry, was used for evaluation of peripheral endothelial function. Enzyme-linked immunosorbent assay (ELISA) was used to measure the level of serum MOTS-C.Results: Levels of serum MOTS-C and RHI were lower in the obese children compared with the healthy children (P < 0.01). The RHI level was independently associated with body mass index, high-density lipoprotein cholesterol, and MOTS-C in linear regression analysis. Further analysis showed a significant mediating effect of MOTS-C on the correlation between body mass index and RHI in children, with the ratio of mediating effect value of 9.12%.Conclusion: These data identify that MOTS-C is a previously unknown regulator in the development process of obesity-induced vascular changes.Keywords: obese, children, mitochondrial-derived peptides, MOTS-C, vascular endothelial function

Ruojing Qian,1– 3,&ast; Zhaoyu Xu,4,&ast; Xingyu Hu,1– 3 Suru Liu,1– 3 Yao Mai,1– 3 Xinzhi Tan,1– 3 Xiaofan Su,1– 3 Mingyan Jiang,1– 3 Wei Tang,1– 3 Weidong Tian,1– 3 Li Xie1– 3 1State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 2Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 3Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 4Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weidong Tian; Li Xie, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-85502156 ; +86-28-85503499, Email drtwd@sina.com; samuel@163.comPurpose: A synergistic antibacterial system employing photocatalytic performance and low-temperature photothermal effect (LT-PTT) with the potential for infectious skin wound healing promotion was developed.Methods: Ag/Ag2O was synthesized with a two-step method, and its physicochemical properties were characterized. After its photocatalytic performance and photothermal effect were evaluated under 0.5 W/cm2 808 nm NIR laser irradiation, its antibacterial activities in both planktonic and biofilm forms were then studied in vitro targeting Staphylococcus Aureus (S. aureus), and the biocompatibility was tested with L-929 cell lines afterward. Finally, the animal model of dorsal skin wound infection was established on Sprague-Dawley rats and was used to assess infectious wound healing promotion of Ag/Ag2O in vivo.Results: Ag/Ag2O showed boosted photocatalytic performance and local temperature accumulation compared with Ag2O when exposed to 0.5 W/cm2 808 nm NIR irradiation, which therefore endowed Ag/Ag2O with the ability to kill pathogens rapidly and cleavage bacterial biofilm in vitro. Furthermore, after treatment with Ag/Ag2O and 0.5 W/cm2 808 nm NIR irradiation, infectious wounds of rats realized skin tissue regeneration from a histochemical level.Conclusion: By exhibiting excellent NIR-triggered photocatalytic sterilization ability enhanced by low-temperature photothermal effect, Ag/Ag2O was promising to be a novel, photo-responsive antibacterial agent.Keywords: semiconductor/metal hybrid, antibacterial agent, photo-responsive antibacterial activity, reactive oxygen species, infectious wound skin model

Objective To evaluate efficacy and safety of the interleukin‐23p19‐subunit inhibitor, guselkumab, in DISCOVER‐1 patients with active psoriatic arthritis (PsA) by prior use of tumor necrosis factor inhibitor (TNFi). Methods The phase 3, randomized, placebo‐controlled DISCOVER‐1 study enrolled patients with active PsA (swollen joint count ≥3, tender joint count ≥3, and C‐reactive protein level ≥ 0.3 mg/dl) despite standard therapies; approximately one‐third could have received two or fewer prior TNFi. Patients were randomized to 100 mg of guselkumab every 4 weeks (Q4W); 100 mg of guselkumab at week 0, at week 4, and every 8 weeks (Q8W); or placebo with crossover to guselkumab Q4W at week 24. Efficacy end points of ≥20% and ≥50% improvement in individual American College of Rheumatology (ACR) criteria and achieving the minimal disease activity (MDA) components were summarized by prior TNFi status. Results In DISCOVER‐1, 118 (31%) patients previously received one or two TNFi. As previously reported, rates for acheiving ≥20% improvement in the composite ACR response at week 24 and week 52 were similar in TNFi‐naive and TNFi‐experienced patients randomized to guselkumab Q4W (76% and 68%, respectively) and Q8W (61% and 58%, respectively). Similar trends were observed for response rates of ≥20% and ≥50% improvement in individual ACR criteria and for achieving individual MDA components at week 24; TNFi‐naive patients were more likely to achieve end points related to physical function and pain than TNFi‐experienced patients. Overall, response rates were maintained or increased through week 52 regardless of prior TNFi use. Through week 60 in guselkumab‐treated TNFi‐naive and TNFi‐experienced patients, 62% and 64%, respectively, reported one or more adverse events (AEs); 4% and 6% had serious AEs, respectively. Conclusion Through 1 year, 100 mg of guselkumab Q4W and Q8W provided sustained improvements across multiple domains in both TNFi‐naive and TNFi‐experienced patients with active PsA.

Li Xie,1 Ehsan Vaghefi,1,2 Song Yang,1 David Han,1,2 John Marshall,3 David Squirrell1,4 1Toku Eyes Limited, Auckland, New Zealand; 2School of Optometry and Vision Science, The University of Auckland, Auckland, New Zealand; 3Institute of Ophthalmology, UCL, London, UK; 4Department of Ophthalmology, Auckland District Health Board, Auckland, New ZealandCorrespondence: Ehsan Vaghefi, Tel +6493737599, Email e.vaghefi@auckland.ac.nzPurpose: To create an ensemble of Convolutional Neural Networks (CNNs), capable of detecting and stratifying the risk of progressive age-related macular degeneration (AMD) from retinal photographs.Design: Retrospective cohort study.Methods: Three individual CNNs are trained to accurately detect 1) advanced AMD, 2) drusen size and 3) the presence or otherwise of pigmentary abnormalities, from macular centered retinal images were developed. The CNNs were then arranged in a “cascading” architecture to calculate the Age-related Eye Disease Study (AREDS) Simplified 5-level risk Severity score (Risk Score 0 – Risk Score 4), for test images. The process was repeated creating a simplified binary “low risk” (Scores 0– 2) and “high risk” (Risk Score 3– 4) classification.Participants: There were a total of 188,006 images, of which 118,254 images were deemed gradable, representing 4591 patients, from the AREDS1 dataset. The gradable images were split into 50%/25%/25% ratios for training, validation and test purposes.Main Outcome Measures: The ability of the ensemble of CNNs using retinal images to predict an individual’s risk of experiencing progression of their AMD based on the AREDS 5-step Simplified Severity Scale.Results: When assessed against the 5-step Simplified Severity Scale, the results generated by the ensemble of CNN’s achieved an accuracy of 80.43% (quadratic kappa 0.870). When assessed against a simplified binary (Low Risk/High Risk) classification, an accuracy of 98.08%, sensitivity of ≥ 85% and specificity of ≥ 99% was achieved.Conclusion: We have created an ensemble of neural networks, trained on the AREDS 1 dataset, that is able to accurately calculate an individual’s score on the AREDS 5-step Simplified Severity Scale for AMD. If the results presented were replicated, then this ensemble of CNNs could be used as a screening tool that has the potential to significantly improve health outcomes by identifying asymptomatic individuals who would benefit from AREDS2 macular supplements.Keywords: AREDS, Simplified Severity Scale, AMD, neural networks

Kai Jiang,1,2 Jing Feng,2 Xia Qi,2 Lili Ran,2 Lixin Xie2 1Department of Ophthalmology, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, People’s Republic of China; 2Eye Institute of Shandong First Medical University, Eye Hospital of Shandong First Medical University, Qingdao, People’s Republic of ChinaCorrespondence: Lixin Xie, Shandong Eye Institute, 5 Yan’erdao Road, Qingdao, 266071, Tel +8613335026472, Email Lixin_xie@hotmail.comPurpose: In search of new potent treatment of herpes simplex keratitis (HSK), inhibitory effect of oridonin (Ori) on herpes simplex virus type 1 (HSV-1) was validated by experiments.Methods: For evaluating inhibitory effect of oridonin on herpes simplex virus type 1, a series of in-vivo and in-vitro studies were carried out. Mouse HSV-1 infection model was used in the in-vivo experiments. Experimental mice were classified in five different groups: Mock (mock-infected), HSV-1+ DMSO, HSV-1+ Ori, HSV-1+ ACV, combined Ori and ACV+HSV-1. Corneas of Mock, HSV-1+ DMSO, HSV-1+ Ori group were sent for mRNA-sequencing after 3 days post infection (dpi). The expression of virus and host-related genes was evaluated by quantitative real-time polymerase chain reaction (qPCR). Vero cells HSV-1 infection models were used in the in-vitro experiments.Results: The application of ACV, Oridonin alone or a combination of both could alleviate HSV-1 severity and inhibit HSV-1 virus replication in C57BL/6 mice models. qPCR showed that compared with mock group, the expression of interleukin-6 (il-6), interleukin-1α (il-1α), and Tumor-necrosis factor-alpha (tnf-α) was up-regulated in DMSO+HSV-1 group and suppressed in other three group. Moreover, the expression of nod-like receptor protein (nlrp3), caspase 1 and interleukin-1β (il-1β) were depressed in the oridonin-treated group. Oridonin significantly inhibits HSV-1 replication, HSV-1 related gene expression, and the production of progeny HSV-1 viruses in vitro. Besides, oridonin affect the replication phase but not HSV-1 entry or penetration and cannot inactivate HSV-1.Conclusion: Oridonin alleviates herpes simplex keratitis infection in mouse, which may be attributed to inhibition of the NLRP3-inflammasome-IL-1β pathway. Our study illustrates that Oridonin has potential promise for application in treating HSK and other diseases caused by HSV-1 infection.Keywords: oridonin, HSV-1, herpes simplex keratitis, herb, nlrp3, inflammasome

Xin Sun, Jie Xu, Lu Xie, Wei Guo Department of Musculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, 100044, People’s Republic of ChinaCorrespondence: Wei Guo, Department of Musculoskeletal Tumor Center, Peking University People’s Hospital, No. 11, Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China, Tel +86 13810548607, Email bonetumor@163.comObjective: This study was to investigate the effectiveness and tolerability of anlotinib plus PD-1 inhibitors for patients with previously treated metastatic soft tissue sarcoma (STS).Methods: Patients with previously treated metastatic STS who were administered with anlotinib plus PD-1 inhibitors in clinical practice were included for analysis retrospectively. All the common subtypes of advanced STS were appropriate for analysis. Efficacy of the regimen was assessed according to the change of target lesion radiologically, and all the patients were followed up regularly. Safety profile during the combination administration was recorded and documented specifically. Clinical significance according to different STS subtypes was analyzed accordingly.Results: From September 2018 to January 2022, a total of 32 patients with previously treated metastatic STS who received anlotinib plus PD-1 blockades were screened for the analysis in this study. The best overall response during the combination administration indicated that partial response was observed in 11 patients, stable disease was noted in 16 patients and progressive disease was found in 6 patients, yielding an objective response rate (ORR) of 34.4% (95% CI: 18.6– 53.2%) and a disease control rate (DCR) of 84.4% (95% CI: 67.2– 94.7%). Furthermore, the median PFS of 32 patients with metastatic STS was 7.6 months (95% CI: 3.31– 11.89) and the median OS was 14.9 months (95% CI: 8.36– 21.44). Besides, adverse reactions related to the treatment during anlotinib plus PD-1 inhibitors administration were observed in 29 patients (90.6%), of whom, a total of 13 patients (40.6%) were deemed as grade 3– 4 adverse reactions and no grade 5 adverse reaction was found. Specifically, the most common adverse reactions were fatigue, hypertension, hand-foot syndrome, diarrhea and dermal toxicity.Conclusion: Anlotinib plus PD-1 inhibitors demonstrated durable and promising efficacy and tolerable safety for patients with metastatic STS in real world. Further prospective clinical trials were warranted to validate the feasibility of anlotinib plus PD-1 blockades clinically.Keywords: soft tissue sarcoma, anlotinib, PD-1 inhibitors, effectiveness, tolerability

Li Li,1 Rongjin Sun,1 Joseph Zenga,2 Heather Himburg,3 Lu Wang,1 Shengnan Duan,1 Jingwen Liu,1 Dinh Bui,1 Zuoxu Xie,1 Ting Du,4 Lijun Xie,1 Taijun Yin,1 Stu Wong,2 Song Gao,4 Ming Hu1 1Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA; 2Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI, USA; 3Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA; 4Department of Pharmaceutical Science, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, USACorrespondence: Ming Hu, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA, Email mhu@uh.edu Song Gao, Department of Pharmaceutical Science, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, USA, Email Song.Gao@tsu.eduObjective: We aim to quantify the absolute protein expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in various cells and tissues to determine the relative contribution of COX-1 and COX-2 to PGE2 production.Methods: An LC-MS method was developed and validated, then used for quantifying the absolute amounts of COX-1 and COX-2 in recombinant human COX-1 and COX-2, lysates from different cells, tissue microsomes of rodents and humans, Pirc rat colonic polyps, and biopsy specimens from squamous cell carcinoma (SCC) patients. The COX-1 and COX-2 turnover numbers were subsequently calculated based on apparent formation rates of PGE2.Results: A robust LC-MS method for quantification of COX-1 and COX-2 was developed and validated and then used to calculate their apparent turnover numbers. The results showed that COX-1 expression levels were much higher than that of COX-2 in all the tested tissues including the colonic epithelium of F344 (28-fold) and Pirc rats (20-fold), colonic polyps of Pirc rats (8-fold), and biopsy specimens of SCC patients (11– 17-fold). In addition, both COX-1 and COX-2 were higher in polyps when compared to adjacent mucosa of Pirc rats. The turnover number of recombinant human COX-2 was 14-fold higher than that of recombinant human COX-1. LPS stimulation increased COX-2 protein expression in three cell lines (Raw 264.7, SCC9 and EOMA) as expected but unexpectedly increased COX-1 protein expression (13.8-fold) in EOMA cells.Conclusion: In human oral cancer tissues and cells as well as Pirc rat colon, COX-1 plays an unexpectedly but more important role than COX-2 in abnormal PGE2 production since COX-1 expression is much higher than COX-2. In addition, COX-1 expression levels are inducible in cells, and higher in polyps than surrounding mucosa in Pirc rat colon. These results indicate that targeted suppression of local COX-1 should be considered to reduce colon-specific PGE2-mediated inflammation.Graphical Abstract: Keywords: cyclooxygenase-1, cyclooxygenase-2, turnover number, inflammation, absolute quantification, liquid chromatography with tandem mass spectrometry

Qi Huang,1 Xingwen Zhang,2 Aijun Jia,2 Qi Huang,3 Yu Jiang,4 Liangyi Xie5 1Department of Pharmacy, Hunan Provincial People’s Hospital (The first-affiliated hospital of Hunan normal university), Changsha, People’s Republic of China; 2Emergency Intensive Care Unit, Hunan Provincial People’s Hospital (The first-affiliated hospital of Hunan normal university), Changsha, People’s Republic of China; 3Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 4Institute of Emergency Medicine, Hunan Provincial People’s Hospital (The first-affiliated hospital of Hunan normal university), Changsha, People’s Republic of China; 5Department of Laboratory Medicine, Hunan Provincial People’s Hospital (The first-affiliated hospital of Hunan normal university), Changsha, People’s Republic of ChinaCorrespondence: Qi Huang, Hunan Provincial People’s Hospital (The first-affiliated hospital of Hunan normal university), Jiefangxi Road N.61, Changsha, Hunan, People’s Republic of China, Tel +86-731-81866105, Email q12600073@163.comObjective: This study aimed to provide feasible suggestions for intraventricular injection of tigecycline to treat intractable Acinetobacter baumannii intracranial infections by studying its pharmacokinetics/pharmacodynamics and neurotoxicity.Methods: A simple and reliable two-dimensional high-performance liquid chromatography (2D-HPLC) method was used to determine tigecycline concentration. The pharmacokinetics (PK) of tigecycline in cerebrospinal fluid (CSF) was investigated by performing therapeutic drug monitoring (TDM). The pharmacodynamics (PD) of tigecycline was evaluated by its minimum inhibitory concentration (MIC) against XDR A. baumannii. CCK8 assay was used to evaluate the cytotoxicity of different concentrations of tigecycline effect on PC12 cells, and apoptosis assay was analyzed by flow cytometry.Results: Tigecycline retention time in 2D-HPLC was 7.636 min. The lower limit of quantitation (LLOQ) was 0.1mg/L, which met the requirements of concentration determination for TDM. The MIC50 and MIC90 values of tigecycline for A. baumannii were 2 and 4 mg/L, respectively. After a dose of 5mg tigecycline, Cmax in CSF was 37.894 mg/L which was high above the MIC values. The t1/2 of tigecycline was estimated to be 2.73 hours. Tigecycline significantly decreased cell viability as assessed and induced apoptosis of the PC12 cell. The IC50 value of PC12 cells treated with tigecycline was about 51.35 mg/L.Conclusion: Intraventricular injection of tigecycline is a promising method for treating XDR A. baumannii intracranial infection. Since a high concentration of tigecycline in CSF may have potential neurotoxicity, and the t1/2 was short, giving small doses of less than 5 mg at least twice a day may be safer and more effective. Intraventricular injection of tigecycline must be selected cautiously and best carried out under TDM.Keywords: tigecycline, intraventricular injection, XDR A. baumannii, intracranial infection, TDM

Rongping Fan,1,2,&ast; Lei Xie,1,2,&ast; Xuemin Peng,1,2 Bo Yu,3 Huajie Zou,1,2,4 Jiaojiao Huang,1,2 Xuefeng Yu,1,2 Daowen Wang,3 Yan Yang1,2 1Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, 430030, People’s Republic of China; 3Division of Cardiology, Department of Internal Medicine and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 4Division of Endocrinology, Department of Internal Medicine, The Affiliated Hospital of Qinghai University, Xining, Qinghai, 810001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Yang; Daowen Wang, Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China, Tel +86-27-83665513, Fax +86-27-83662883, Email yangyan6910@163.com; dwwang@tjh.tjmu.edu.cnAim: To explore the clinical outcomes among preadmission insulin-treated type 2 diabetes mellitus (T2DM) in intensive care units (ICU).Patients and Methods: In this retrospective observational study, 578 T2DM patients admitted to ICU were recruited from March 2011 to February 2021, which were composed of 528 patients treated with insulin after ICU admission (including 300 preadmission non-insulin-treated and 228 preadmission insulin-treated patients) and 50 patients treated without insulin before and after ICU admission. Clinical outcomes were compared between the groups. Variables of age (± 10 years), gender, blood glucose > 10 mmol/l on ICU admission, and original comorbidities were used for matching to get the 1:1 matched cohort. The Kaplan–Meier survival curves were graphed to describe the survival trend and Cox regression analysis was performed to get adjusted hazard ratio (HR).Results: Compared with the preadmission non-insulin-treated T2DM patients, preadmission insulin-treated T2DM patients had higher incidence of hypoglycemia [14.5% (33/228) vs 8.7% (26/300); p = 0.036]. In the 1:1 matched cohort, the preadmission insulin-treated T2DM patients had significantly increased mortality rate [30.0% (45/150) vs (16.0% (24/150)); adjusted HR, 1.68 (1.01– 2.80)] than preadmission non-insulin-treated T2DM patients. Compared with T2DM patients treated without insulin before and after ICU admission, preadmission insulin-treated T2DM patients had higher mortality and longer length of ICU stay (all p < 0.05).Conclusion: Preadmission insulin treatment was associated with increased mortality rate and longer length of ICU stay among T2DM patients in ICU. Preadmission insulin-treated T2DM patients might have worse clinical outcomes when they are critically ill.Keywords: insulin treatment, intensive care units, type 2 diabetes mellitus, mortality, ICU stay

Yu Gong,1,&ast; Liangyu Xie,2,&ast; Shengqiang Yu2 1Department of Internal Medicine, Division of Nephrology, Telemedicine Center, Shanghai Municipal Eighth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Internal Medicine, Division of Nephrology, Shanghai Changzheng Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Gong, Department of Internal medicine, Division of Nephrology, Telemedicine Center, Shanghai Municipal Eighth People’s Hospital, 8 Caobao Road, Shanghai, 200235, People’s Republic of China, Tel +86-18930718612, Email gyfd66@sina.com Shengqiang Yu, Department of Internal Medicine, Division of Nephrology, Shanghai Changzheng Hospital, Shanghai, 200003, People’s Republic of China, Tel +86-17301621966, Email shyusqczh@163.comBackground: Older patients with chronic renal failure (CRF) which currently is referred to as end-stage renal disease (ESRD) are associated with higher mortality. In-center nocturnal dialysis (INHD) is a new blood purification model, which is characterized by longer sessions and nighttime administration. However, no data for the efficacy of INHD in older patients with ESRD are available. This study is to analyze the effect of INHD in the treatment of older patients with ESRD.Methods: A retrospective, observational study was conducted in a university teaching hospital. Seventy-two patients with ESRD receiving INHD were enrolled. They were divided into the older ESRD patients (age ≥ 60) group (n = 22) and the non-older ESRD patients (age < 60) group (n = 50). The causes of older ESRD patients and non-older ESRD patients receiving INHD were analyzed. Differences of laboratory test indicators of older patients with ESRD before INHD and after INHD were compared. Quality of life for older ESRD patients receiving INHD was assessed by using the Kidney Disease Quality of Life-36 Instrument (KDQOL-36).Results: Serum concentration of hemoglobin and serum concentration of albumin of older patients with ESRD increased significantly after INHD (p < 0.05). There were similar results in the non-older cohort (p ≤ 0.05). Scores of five KDQOL-36 subscales increased significantly after INHD (p ≤ 0.001) indicated that the quality of life for old patients with ESRD was significantly improved after INHD.Conclusion: INHD is an effective blood purification therapy that can improve the condition of renal anemia, and it may provide a potential positive impact in the malnutrition of older and non-older patients with ESRD. INHD can improve the quality of life of older patients with ESRD. The results will provide a basis for formulating new policies of blood purification therapy for older patients.Keywords: older patients, chronic renal failure, CRF, end-stage renal disease, ESRD, in-center nocturnal hemodialysis, INHD, quality of life, nocturnal home hemodialysis, NHHD

Yu Zhang,1– 3,&ast; Li Cui,2,&ast; Yizeng Lu,4 Jixiang He,5 Hidayat Hussain,6 Lei Xie,4 Xuan Sun,2 Zhaoqing Meng,7 Guiyun Cao,7 Dawei Qin,1 Daijie Wang2,3 1School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, People’s Republic of China; 2School of Pharmaceutical Sciences and Key Laboratory for Applied Technology of Sophisticated Analytical Instruments of Shandong Province, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250014, People’s Republic of China; 3Biological Engineering Technology Innovation Center of Shandong Province, Heze Branch of Qilu University of Technology (Shandong Academy of Sciences), Heze, 274000, People’s Republic of China; 4Shandong Provincial Center of Forest and Grass Germplasm Resources, Jinan, 250102, People’s Republic of China; 5School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250353, People’s Republic of China; 6Department of Bioorganic Chemistry, Leibniz Institute of Plant BioChemistry, Halle, D-06120, Germany; 7Shandong Hongjitang Pharmaceutical Group Co., Ltd., Jinan, 250103, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dawei Qin, School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, People’s Republic of China, Tel/Fax +86 53189631208, Email qdw@qlu.edu.cn Daijie Wang, Biological Engineering Technology Innovation Center of Shandong Province, Heze Branch of Qilu University of Technology (Shandong Academy of Sciences), Heze, 274000, People’s Republic of China, Tel +86 53182605319, Fax +86 53182964889, Email wangdaijie@qlu.edu.cnBackground: The leaves of L. japonica (LLJ) are widely used as medicine in China. It is rich in caffeoylquinic acids, flavonoids and iridoid glycosides and has strong reducing capacities. Therefore, it can be used as a green material to synthesize silver nanoparticles.Methods: LLJ was used as a reducing agent to produce the LLJ-mediated silver nanoparticles (LLJ-AgNPs). The structure and physicochemical properties of LLJ-AgNPs were characterized by ultraviolet spectroscopy (UV-Vis), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and x-ray powder diffraction (XRD). Antioxidant activity of LLJ-AgNPs was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging. Antibacterial activity was determined by 96 well plates (AGAR) gradient dilution, while the anticancer potential was determined by MTT assay.Results: The results showed LLJ-AgNPs had a spherical structure with the maximum UV-Vis absorption at 400 nm. In addition, LLJ-AgNPs exhibited excellent antioxidant properties, where the free radical scavenging rate of LLJ-AgNPs was increased from 39% to 92% at concentrations from 0.25 to 1.0 mg/mL. Moreover, LLJ-AgNPs displayed excellent antibacterial properties against E. coli and Salmonella at room temperature, with minimum inhibitory values of 10− 6 and 10− 5 g/L, respectively. In addition, the synthetic LLJ-AgNPs exhibited a better inhibition effect in the proliferation of cancer cells (HepG2, MDA-MB − 231, and Hela cells).Conclusion: The present study provides a green approach to synthesize LLJ-AgNPs. All those findings illustrated that the produced LLJ-AgNPs can be used as an economical and efficient functional material for further applications in food and pharmaceutical fields.Keywords: leaves of Lonicera japonica Thunb, LLJ-AgNO3-NPs, green approach, antioxidant, antibacterial, anticancer

Hui Li,1 Lu Xie,1 Hongdi Yao,2 Lexing Zhang,3 Sanhong Liang,1 Wen Lyu1 1Department of Gastroenterology, Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Zhejiang Chinese Medical University School, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Radiology, Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Wen Lyu, Department of Gastroenterology, Hangzhou First People’s Hospital, Zhejiang University School of Medicine, 4 Xueshi Road, Shangcheng District, Hangzhou, 310000, Zhejiang, People’s Republic of China, Email lihui-cy@163.comBackground: The incidences of enterovesical and enterocutaneous fistulas are extremely low, and enterovesical and enterocutaneous fistulas are difficult to treat in patients with Crohn’s disease.Case Summary: In this case, the patient had recurrent abdominal pain and diarrhea for more than 2 years, with fecal residue in the urine for 6 days. Pelvic magnetic resonance imaging and colonoscopy showed intestinal infection with a rectal fistula, and the initial diagnosis was severely active Crohn’s disease with an enterovesical fistula. The patient had multiple internal fistulas and infections, and strongly refused surgical conditions. The patient was given an intravenous infusion of ustekinumab and somatostatin, with anti-infective treatment, nutritional support and regulation of the intestinal flora. Drainage and debridement of the cutaneous fistula were performed. After comprehensive treatment and management, the patient’s condition achieved significant clinical remission.Conclusion: This patient achieved clinical response and will receive follow-up for another dose of ustekinumab after 12 weeks. The patient developed enterovesical and enterocutaneous fistulas, the incidence of multiple fistulas which are low in patients with CD and are difficult to cure and prone to relapse. Only few patients achieve complete remission. At present, there is no standard and effective treatment for CD with multiple fistulas. Usually, surgery is performed for treatment. Drug therapy, especially with biological agents, should be selected as the first-line pre-operative treatment. Clinicians, especially gastroenterologists, need to improve their knowledge of these conditions and update the treatment consensus guidelines in a timely manner. Clinicians need to take into account the patient’s condition and willingness when developing an effective treatment plan.Keywords: Crohn’s disease, enterovesical fistula, enterocutaneous fistula, ustekinumab, therapy

Da-Ming Xu,1,&ast; Ze-Wen Zhang,2,&ast; Jing-Xing Yi,3 Long Xie,3 Wen-Jun Yu,2 Jin-Feng Qiu,4 Cheng-Wei Xu,5 Chun-Ling He,6 Xian-Ru Xu,7 Jun Yin3 1Division of Urological Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, People’s Republic of China; 2Division of Hematology, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, People’s Republic of China; 3Department of Clinical Laboratory Medicine, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, People’s Republic of China; 4Division of Respirology, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, People’s Republic of China; 5Department of Blood Purification, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, People’s Republic of China; 6Department of Pathology, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, People’s Republic of China; 7Division of Inventional Ultrasonic Therapeutics, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Yin, Department of Clinical Laboratory Medicine, The Second Affiliated Hospital of Shantou University Medical College, Dongxia Road North, Shantou, Guangdong Province, 515041, People’s Republic of China, Tel +86 754 8891 5950, Email jyin@stu.edu.cnBackground: Adult chronic immune thrombocytopenia (chronic ITP) is a common autoimmune hemorrhagic disease characterized by decreased platelet production and increased platelet destruction, leading to thrombocytopenia. In this study, Ca2+, calnexin (CNX) and calreticulin (CRT) within platelets from adult patients with chronic ITP were investigated.Methods: Platelets were isolated from blood specimen collected from 20 adult patients with chronic ITP and 20 healthy volunteers. Ca2+, CNX and CRT were determined by flow cytometry, and the results were analyzed with EXPO32 ADC software.Results: Flow cytometry showed the expressions of Ca2+ (74.19± 19.40% vs 22.79± 10.47%) was elevated (P< 0.05). However, CNX (15.10± 7.32% vs 41.79± 14.45%) and CRT (25.11± 12.66% vs 38.58± 12.02%) were decreased markedly in platelets from adult patients with chronic ITP (P< 0.05 compared with healthy volunteers).Conclusion: Based on enhanced expression of Ca2+ and attenuated expression of CNX and CRT in patients with chronic ITP, Ca2+ concentration and its associated down-regulated proteins may be important regulatory signals in the pathogenesis of chronic ITP.Keywords: platelets, chronic immune thrombocytopenia, Ca2+, calnexin, calreticulin

Objective Evaluate relationship between radiographic progression and clinical outcomes in post hoc analyses of patients with psoriatic arthritis (PsA) receiving up to 2 years of guselkumab therapy in the phase 3, placebo-controlled, randomised trial, DISCOVER-2.Methods Biologic-naïve adults with active PsA (≥5 swollen joints /≥5 tender joints ; C reactive protein ≥0.6 mg/dL) were randomised to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at week 0, week 4, then every 8 weeks (Q8W); or placebo→guselkumab 100 mg Q4W (week 24). Radiographs (hands/feet) at week 0, week 24, week 52 and week 100 were scored via PsA-modified van der Heijde-Sharp (vdH-S) methodology. In these post hoc analyses, mean changes in vdH-S scores were summarised according to achievement of American College of Rheumatology 20/50/70 response; low disease activity (LDA) defined by Disease Activity in Psoriatic Arthritis (DAPSA) ≤14 or Psoriatic ArthritiS Disease Activity Score (PASDAS) ≤3.2, or minimal/very low disease activity (MDA/VLDA); and normalised physical function (Health Assessment Questionnaire-Disability Index (HAQ-DI) ≤0.5). Response rates for achieving MDA/VLDA and each component were determined among patients with and without radiographic progression (change in total vdH-S score >0.5). No formal hypothesis testing was performed.Results 664 of 739 treated patients in DISCOVER-2 continued study treatment at week 52 and were included in these analyses. Mean changes in vdH-S scores from weeks 0 to 100 among all patients in the Q4W and Q8W groups were 1.7 and 1.5, respectively. Among all guselkumab-randomised patients, those who achieved ACR20/50/70, DAPSA LDA, PASDAS LDA, MDA, VLDA and HAQ-DI ≤0.5 (normalised physical function) had smaller mean changes in vdH-S scores than did non-responders at week 52 (0.2–1.2 vs 1.7–4.1) and week 100 (0.3–1.2 vs 2.0–4.6). Relative to patients with radiographic progression, those without progression were more likely to achieve the MDA criteria related to swollen and tender joint counts, patient-reported pain and global assessment, and normalised physical function through week 100.Conclusion In these post hoc analyses, the achievement of low levels of disease activity, including MDA, was associated with diminished rates of radiographic progression observed in patients receiving up to 2 years of guselkumab. Radiographic non-progressors were more likely to achieve patient-reported MDA criteria of minimal pain and normalised physical function compared with radiographic non-responders.Trial registration number NCT03158285.

Chenyang Li,1 Liang Xie,2 Shaomei Shang,1 Xiaosong Dong,3 Xiaoling Wang,4 Long Zhao,3 Chi Zhang,3 Fang Han3 1Peking University School of Nursing, Beijing, People’s Republic of China; 2Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 3Sleep Medicine Center, Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 4PKU-UPenn Sleep Center, Peking University International Hospital, Beijing, People’s Republic of ChinaCorrespondence: Fang HanSleep Medicine Center, Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of ChinaEmail hanfang1@hotmail.comObjective: This study aimed to translate and validate the narcolepsy quality-of-life instrument with 21 questions (NARQoL-21) in Chinese pediatrics with narcolepsy.Methods: NARQoL-21 was translated following the 10 steps of scale translation. The translated version was tested by exploratory factor analysis (EFA), confirmatory factor analysis (CFA), known-group validity, criterion validity, Cronbach’s α and test-rest reliability.Results: The Chinese version of NARQoL-21 consisted of two factors: (psychosocial factors and future outlook factor), including 20 items. EFA yielded 3 domains for psychosocial factors and 1 domain for future outlook factor. The Chinese version had a negative correlation with the overall Modified Epworth Sleepiness Scale (r = − 0.518, p< 0.001) and meaningful difference in score between drug naïve and treated group (p< 0.05). The Cronbach’s α coefficient was higher than 0.7 and intraclass correlation coefficient (ICC) ranged from 0.75 to 0.905, indicating that it had good reliability.Conclusion: The Chinese version of the NARQoL-21 is available and can be used to evaluate the health-related quality of life (HRQoL) of pediatric narcoleptics, despite that there is a shift in factors compared to the English version due to cultural differences. Future studies are recommended to further validate the scale in Chinese pediatrics with narcolepsy.Keywords: narcolepsy, pediatrics, quality of life, validation study

Wenshu Cheng,1,&ast; Xinyue Xu,1,&ast; Yuanyuan Lang,2,&ast; Zugen Cheng,1 Mohammad Rizwan,1 Xiaomin Tang,1 Lixin Xie,1 Yanling Liu,1 Hengyi Xu,3 Yang Liu1 1Department of Pediatrics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330006, People’s Republic of China; 2Medical Imaging Center, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330006, People’s Republic of China; 3State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi Province, 330047, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang LiuDepartment of Pediatrics, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Donghu District, Nanchang, Jiangxi Province, People’s Republic of ChinaTel +0086-791-8631-1209Email ocean3166@yeah.netPurpose: To evaluate the effects of anatase and rutile TiO2 nanoparticles (NPs) on the growth and development of bones in young rats and explore their possible mechanisms.Methods: Three-week-old male rats were orally administered anatase TiO2 NPs and rutile TiO2 NPs for 28 days. The indicators of rat growth and development, liver function, bone metabolism, and insulin-like growth factor-1 (IGF-1) levels were evaluated. Micro-computed tomography (micro-CT) and immunohistochemistry were used to evaluate the tibia.Results: No significant differences were observed among growth and development indicators in young rats. Significant differences were found in IGF-1 levels, phosphorus levels, and liver function. Micro-CT revealed osteoporosis in the bones. The micro-CT data supported the same result. Bone immunohistochemistry results showed that the expression of osteoprotegerin (OPG) was decreased and the expression of receptor activator of nuclear factor-κB ligand (RANKL) and cathepsin K (CTSK) was increased.Conclusion: This study demonstrated that TiO2 NPs can damage bones via the IGF-1/OPG/RANKL/CTSK pathway in young rats. Furthermore, rutile TiO2 NPs damaged the bones more seriously than anatase TiO2 NPs.Keywords: TiO2 NPs, different crystal forms, IGF-1/OPG/RANKL/CTSK pathway, young rats, bone growth

Da-Ming Xu,1,&ast; Qian Li,2,&ast; Jing-Xing Yi,3,&ast; Xin-Jian Cai,3 Long Xie,3 Wei Fang,3 Jin-Feng Qiu,4 Cheng-Wei Xu,5 Chun-Ling He,6 Xian-Ru Xu,7 Jie-Song Xu,8 Jun Yin2,3 1Division of Urological Surgery, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 2Division of Hematology, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 3Department of Clinical Laboratory Medicine, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 4Division of Respirology, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 5Department of Blood Purification, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 6Department of Pathology, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 7Division of Interventional Ultrasonic Therapeutics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 8Department of Electroencephalogram, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun YinDepartment of Clinical Laboratory Medicine and Division of Hematology, Second Affiliated Hospital of Shantou University Medical College, Dongxia Road North, Shantou, Guangdong Province, 515041, People’s Republic of ChinaTel +86 754 8891 5950Email jyin@stu.edu.cnObjective: In order to evaluate the effect of dyslipidemia on cellular or humoral immunity in patients, changes in the absolute number of lymphocyte subsets were detected.Methods: Flow cytometry was applied to determine the absolute value of lymphocyte subsets: B cell, NK cell, CD4+ T cell including the functional subset (CD4+CD28+), native subset (CD4+CD45RA+CD62L+), memory T cell subset (CD4+CD45RA−), CD8+ T cell including the functional subset (CD8+CD28+) and activated subsets (CD8+CD38+ and CD8+DR+). The relationship between lymphocyte subsets and hypercholesterolemia and hypertriglyceridemia was analyzed.Results: The absolute values of CD19+ B cell, CD3+ T cell, CD4+ Th cell, CD4+CD28+ cell, naive CD4+ T cell and memory CD4+ T cell in patients with dyslipidemia were markedly higher than those in healthy controls (P< 0.05). There was no significant difference between healthy controls and dyslipidemia patients in other lymphocyte subsets (P> 0.05). The absolute values of CD3+ T cell and naive CD4+ T cell were significantly positively correlated with hypercholesterolemia in peripheral blood (r=0.291 and 0.306, respectively, all P< 0.05). There was no significant correlation between hypertriglyceridemia and lymphocyte subsets (P> 0.05).Conclusion: Dyslipidemia has potential effects on immune profiles in lymphocytes subsets, and changes in lymphocyte subsets in dyslipidemia patients may lead to immune dysfunction.Keywords: dyslipidemia, lymphocyte subsets, flow cytometry

Ning Guan,1,&ast; Haiying Zheng,2,&ast; Xiaoling Wu,3 Longfei Xie,4 Xiaojing Tong5 1Department of Physical Examination Center, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Liaoning, 110042, People’s Republic of China; 2Department of the Traditional and Modern Treatment Center, The Affiliated Shenben Hospital of Liaoning University of Traditional Chinese Medicine, Liaoning, 110031, People’s Republic of China; 3Department of Gynecology, The Second People’s Hospital of Baise, Guangxi, 533100, People’s Republic of China; 4Department of Physics and Integrative Biology, University of California, Berkeley, CA, 94720, USA; 5Department of Gynecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Liaoning, 110042, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaojing TongDepartment of Gynecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Liaoning, 110042, People’s Republic of ChinaTel +86 24 15542 253448Email adnikenike@sina.comObjectives: Long non-coding RNAs (lncRNAs) play a crucial part in cancer progression. However, in epithelial ovarian carcinoma (EOC), the role of SNHG22 needs to be further explained.Methods: Quantitative real-time PCR was used to detect the expression of SNHG22. EOC cells were stably transfected with lentivirus approach and cell proliferation, glycolysis and cell apoptosis, as well as tumorigenesis in animal were performed to assess the effects of SNHG22 in EOC. Chromatin immunoprecipitation (ChIP) and luciferase reporter assay were conducted to confirm the relationship between SP1 and SNHG22.Results: Higher expressed SNHG22 was associated with a poor prognosis in EOC tissues. SNHG22 facilitated glycolysis and proliferation. Mechanistically, LDHA deficiency and glycolysis inhibitor (2-DG, 3-BG) partly rescued proliferation. SP1 mediated SNHG22 expression at the transcriptional level and the SNHG22 promoter region (− 900∼ − 600) was necessary for SP1 binding. Hypoxia and HIF-1α also upregulated SNHG22 expression.Conclusion: SNHG22 is an independent prognostic biomarker for EOC. SNHG22 promotes EOC progression and is a prospective therapeutic target.Keywords: hypoxia, SNHG22, SP1, epithelial ovarian carcinoma, glycolysis

Xiacan Chen,1 Wanjun Guo,2 Liangming Yu,2 Dan Luo,2 Leling Xie,2 Jiajun Xu2 1Institute of Forensic Medicine, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, People’s Republic of China; 2Mental Health Centre, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Jiajun XuMental Health Centre, West China Hospital, Sichuan University, 610041, People’s Republic of ChinaEmail xujiajun120@126.comObjective: The findings of olfaction are inconsistent in anxiety disorders, and few studies have reported on the olfactory performance in generalized anxiety disorder (GAD). Therefore, we aim to investigate the olfactory function of patients with GAD and the association between olfactory function and anxiety symptoms.Methods: We conducted a case–control study by selecting 107 patients with GAD and 107 healthy controls matched for sex and age, to investigate olfaction deficits in GAD and the association between anxiety severity and olfaction. All patients were treatment-naïve prior to the inclusion. Anxiety severity and olfaction were assessed by the Hamilton anxiety rating scale (HAM-A) and the Sniffin’ Sticks test (SST), respectively. Partial correlations were used to analyze the relationship between olfaction and anxiety severity. False discovery rate (FDR) correction was used in multi-correlation analyses.Results: Compared with healthy controls, patients in the GAD group demonstrated odor threshold, discrimination and identification deficits. In the moderate/severe anxiety subgroup, discrimination score was significantly and inversely correlated with the somatic anxiety score (γ=− 0.44, q = 0.03), and identification score was significantly and inversely correlated with the HAM-A total score (γ=− 0.42, q= 0.04). The TDI score (the sum of threshold, discrimination and identification scores) was significantly and inversely correlated with the somatic (γ=− 0.44, q = 0.04) and psychic (γ=− 0.45, q = 0.04) anxiety scores in the moderate/severe anxiety subgroup.Conclusion: This study demonstrated the olfactory impairment in patients with GAD and that poorer odor discrimination was correlated with greater severity of somatic anxiety.Keywords: GAD, olfaction, symptom

Yibing Chen,1 Weifang Wang,1 Yutao Guo,2 Hui Zhang,2 Yundai Chen,2 Lixin Xie3 1Department of Respiratory and Critical Care Medicine, Senior Department of Respiratory and Critical Care Medicine, The First Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 2Senior Department of Cardiology, The Six Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 3Senior Department of Respiratory and Critical Care Medicine, The Eighth Medical Center PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Lixin XieSenior Department of Respiratory and Critical Care Medicine, The Eighth Medical Center PLA General Hospital, Beijing, People’s Republic of ChinaTel +86 13911252807Email xielx301@126.comYundai ChenSenior Department of Cardiology, the Six Medical Center of PLA General Hospital, Beijing, People’s Republic of ChinaTel +86 13311119778Email cyundai@vip.163.comBackground: Obstructive sleep apnea (OSA), the most common upper-airway disease, is closely associated with the risk of cardiovascular diseases. However, the early screening of OSA is a main challenge, relying on polysomnography (PSG) or home sleep apnea test (HSAT) in hospitals. Photoplethysmography (PPG) has been developed as a novel technology for screening of OSA, while the validation of PPG-based smart devices is limited compared to that for PSG or HSAT devices.Objective: This study aimed to investigate the feasibility and validity of a PPG-based smartwatch in the screening of OSA.Methods: A total of 119 patients were recruited from the Chinese People’s Liberty Army General Hospital (Beijing, China). Among them, 20 patients were assessed for a whole-night sleep study by a smartwatch and PSG simultaneously, as well as 82 cases by a smartwatch and HSAT simultaneously. Using PSG or HSAT as the “gold standard”, we compared the accuracy, sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and positive likelihood ratio (+LR) or negative likelihood ratio (-LR) at three apnea hypopnea index (AHI) levels: AHI≥ 5, AHI≥ 15, and AHI≥ 30.Results: A total of 17/119 patients were excluded from the study due to the poor quality of PPG signals. Among the remaining cases, 83 patients were diagnosed with OSA. Compared to HSAT device, the accuracy, sensitivity, and specificity of the PPG-based smartwatch in predicting moderate-to-severe OSA patients (AHI≥ 15) were 87.9%, 89.7%, and 86.0%, respectively. Compared to PSG device, the accuracy, sensitivity, and specificity of the PPG-based smartwatch in predicting OSA in patients (AHI≥ 5) were 81.1%, 76.5%, and 100%, respectively.Conclusion: The PPG-based smartwatch outperformed in terms of detecting OSA; nevertheless, validation in a large-scale population is imperative.Trial Registration: Chinese Clinical Trial Registry of the International Clinical Trials Registry Platform of the World Health Organization ChiCTR-OOC-17014138; http://www.chictr.org.cn/showprojen.aspx?proj=24191.Keywords: obstructive sleep apnea, photoplethysmography, polysomnography, home sleep apnea test, pulse oximeter, sleep