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Song Song,1,* Honghong Xu,1,* Jiawei Cao,2,* Guanghong Wu,2 Haiyan Sun,1 Xiaoqi Dai,1 Xuekui Li,1 Meng Chen,1 Menghan Zhang,1 Yueming Yan,1 Jingfeng Tong,3 Zhongdong Wang1 1Institute of Tuberculosis Control, Qingdao Preventive Medicine Research Institute, Qingdao Municipal Center for Disease Control and Prevention, Qingdao, People’s Republic of China; 2Department of Laboratory Medicine, Qingdao Chest Hospital, Qingdao, Shandong, People’s Republic of China; 3Department of Medical Affairs, Shanghai Conlight Medical Co., Ltd., Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhongdong Wang, Institute of Tuberculosis Control, Qingdao Preventive Medicine Research Institute, Qingdao Municipal Center for Disease Control and Prevention, No. 8, Fengxian Road, Jinhu Road Street, Shinan District, Qingdao City, Shandong Province, 266000, People’s Republic of China, Email jkzxtb1@163.comPurpose: Nucleotide-based matrix-assisted laser desorption ionization time-of-flight mass spectrometry (nucleotide MALDI-TOF MS) is an emerging molecular technology used for the diagnosis of tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB)and its drug resistance. This study aimed to compare the ability of nucleotide MALDI-TOF MS to detect rifampicin (RIF) resistance in drug-resistant TB (DR-TB) patients with Xpert MTB/RIF and to analyze the disparate results individually. Additionally, potential factors associated with rifampicin resistance among DR-TB patients in Qingdao were investigated.Patients and Methods: A retrospective study was conducted at Qingdao Chest Hospital, and patients with DR-TB were enrolled. Corresponding frozen isolates were recovered and subjected to nucleotide MALDI-TOF MS, Xpert MTB/RIF, and phenotypic drug susceptibility testing (pDST). Sanger sequencing was performed for the discordant results of nucleotide MALDI-TOF MS and Xpert MTB/RIF. Univariate and multivariate logistic regression analyses were used to identify potential factors associated with rifampicin resistance among patients with DR-TB.Results: A total of 125 patients with DR-TB (18.8%, 125/668) were enrolled in this study from May 1 to July 31, 2023. Rifampicin-resistant (DR-TB/RR, 29) and rifampicin-sensitive (DR-TB/RS, 96) groups were divided according to the pDST results. Nucleotide MALDI-TOF MS performed better than Xpert MTB/RIF in terms of sensitivity, specificity, accuracy, and agreement with pDST. Only six cases had inconsistent results, and the sequencing results of five cases were identical to nucleotide MALDI-TOF MS. Furthermore, chest pain (aOR=12.84, 95% CI, 2.29– 91.97, p=0.005), isoniazid sensitivity (aOR=0.14, 0.02– 0.59, p=0.013), and ethambutol sensitivity (aOR=0.02, 0.00– 0.10, p=0.000) were potential factors associated with rifampicin resistance among DR-TB patients in Qingdao.Conclusion: The overall concordance between nucleotide MALDI-TOF MS and Xpert MTB/RIF was 95.2%, with the former performing better in determining rifampicin susceptibility among DR-TB cases in Qingdao. Chest pain, isoniazid, and ethambutol resistance might be factors associated with RIF resistance among patients with DR-TB in Qingdao.Keywords: MTB, rifampicin, nucleotide MALDI-TOF MS, Xpert MTB/RIF, comparison, risk factors

Qian Gui,1,* Jingcai Meng,2,* Mingqiang Shen,1 Hongxuan Feng,1 Xiaofeng Dong,1 Daqiang Xu,3 Wenxin Zhu,2 Qingzhang Cheng,1 Linhui Wang,2 Guanhui Wu,1 Yanli Lu3 1Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, Jiangsu, 215002, People’s Republic of China; 2Department of Physiology and Neurobiology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215123, People’s Republic of China; 3Department of Radiology, the Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, Jiangsu, 215002, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanli Lu, Department of Radiology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), 26 Daoqian Street, Suzhou City, Jiangsu Province, People’s Republic of China, Tel +8618251135654, Email luyanli.2009@163.com Guanhui Wu, Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), 26 Daoqian Street, Suzhou City, Jiangsu Province, People’s Republic of China, Email ghwusz26@njmu.edu.cnIntroduction: Previous studies have predominantly explored the relationship of the glymphatic system with motor symptoms in Parkinson’s disease (PD); however, research on non-motor symptoms remains limited. Therefore, this study investigated the association between glymphatic function and non-motor symptoms, including cognitive impairment and sleep disorders, in PD patients.Methods: This study recruited 49 PD patients and 38 healthy controls (HC). Glymphatic function was evaluated using enlarged perivascular spaces (EPVS) in the basal ganglia (BG) region and diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Cognition, sleep, anxiety, and depression scales were assessed in all participants. According to the scale scores, PD patients were further divided into several groups to identify the presence of non-motor symptoms. Differences in EPVS numbers and ALPS index between PD subgroups and HC group were compared. Spearman correlation analysis was performed to investigate the association between the PD non-motor symptoms and ALPS index. Additionally, receiver operating characteristic (ROC) curves analysis was conducted for ALPS index to predict cognitive impairment and insomnia in PD patients.Results: PD patients with and without non-motor symptoms all showed more EPVS numbers than the controls, and the EPVS numbers in PD patients with cognitive impairment were also greater than those without. Notably, except for the depression subgroup, PD patients with non-motor symptoms showed significantly lower ALPS index than the controls. The Montreal Cognitive Assessment (MoCA) scores were positively correlated, whereas the Parkinson’s Disease Sleep Scale (PDSS)-2 and REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) scores were negatively correlated with the ALPS index in PD patients (r=0.3618, P=0.0053; r=− 0.4146, P=0.0015; r=− 0.2655, P=0.0326, respectively). The ALPS index proved to be predictive of cognitive impairment and insomnia in PD patients (AUC=0.7733, P=0.001; AUC=0.7993, P=0.0004, respectively).Conclusion: Glymphatic function is closely associated with cognition and sleep of PD patients.Keywords: glymphatic system, parkinson’s disease, non-motor symptoms, cognition, sleep

Weixiong Chen,1,2,* Jianqiang Liang,3,* Shuang He,1,4,5 Qingsong Liang,1,4,5 Wenting Tian,6 Aobo Lu,1 Demin Li,1 Zhicheng Huang,1 Guanyi Wu1,4,5 1College of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530299, People’s Republic of China; 2School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, People’s Republic of China; 3Department of Dermatology, the First People’s Hospital of Yulin, Yulin, Guangxi, 537000, People’s Republic of China; 4Key Laboratory for Complementary and Alternative Medicine Experimental Animal Models of Guangxi, Nanning, Guangxi, 530299, People’s Republic of China; 5Guangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Nanning, Guangxi, 530299, People’s Republic of China; 6College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530299, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guanyi Wu, College of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530299, People’s Republic of China, Email wugy@gxtcmu.edu.cnPurpose: Psoriasis is an immune-related disorder characterized by silver scales, epidermis thickness, and itching. She-Chuang-Si-Wu-Tang (SSWT), a traditional Chinese medicine decoction, has been used clinically for 400 years. Although it benefits psoriasis treatment, the mechanism of action is still unclear. This study explores SSWT’s molecular mechanism in treating psoriasis through network pharmacology analysis and experiments.Methods: We identified relevant SSWT and psoriasis targets using network pharmacology and conducted SSWT quality control with high-performance liquid chromatography (HPLC). A mouse model of psoriasis was established using imiquimod (IMQ), with the drug administered continuously for seven days, spanning an eight-day period. During the experiment, we observed spontaneous scratching behaviors and assessed the Psoriasis Area and Severity Index (PASI) scores. At the conclusion of the experiment, we examined skin tissue pathology under an optical microscope and measured epidermal thickness. Additionally, we used enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to measure interleukin (IL)-23, IL-17A, IL-17F, and interferon (IFN)-γ levels in the mice’s serum and their mRNA expression in the skin. Western blot analysis was conducted to assess protein levels related to signaling pathways.Results: Results indicate that SSWT may target IL-17 signaling pathways and T helper (Th) 17 cell differentiation, as predicted by network pharmacology. SSWT significantly improved the PASI and Baker scores, reduced epidermal thickness, and decreased spontaneous scratching in IMQ-induced mice. Additionally, SSWT treatment significantly lowered the concentrations of inflammatory factors in the serum and skin lesions, as well as mRNA expression levels, compared to the IMQ group. Furthermore, SSWT significantly inhibited the phosphorylation of both the signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase (MAPK) pathways.Conclusion: In summary, this study unveiled the potential anti-psoriatic mechanism of SSWT, offering new evidence for its clinical application. Keywords: She-Chuang-Si-Wu-Tang, psoriasis, inflammation, itch, STAT3, MAPK

Yapu Liu, Yuanyuan Su, Zhonghao Luan, Xiuwei Hou, Guangliang Wu, Yonghui Xu, Songmao Wang, Lifeng Gao, Xiaochen Zheng Department of Spinal Surgery, Second Affiliated Hospital of Luohe Medical College, Luohe, People’s Republic of ChinaCorrespondence: Yapu Liu, Department of Spinal Surgery, Second Affiliated Hospital of Luohe Medical College, 463 Haihe Avenue, Luohe, 462300, People’s Republic of China, Tel/Fax +86-0395-6162312, Email 460547380@qq.comPurpose: To introduce the surgical methods and clinical results of percutaneous vertebroplasty (PVP) combined with hollow screw placement as a treatment for patients with Kummell’s disease and pedicle rupture.Methods: From January 2020 to January 2023, a total of 10 patients with Kummell’s disease and pedicle rupture confirmed via imaging underwent three-column intensive therapy using hollow screws combined with PVP. There were two males and eight females with an average age 75.7± 6.11 years old. The time of operation, bone cement injection amount, bone cement leakage during operation were recorded. X-ray and CT were reexamined after operation. The improvement in quality of life was assessed using the Oswestry Disability Index (ODI), and the improvement in low back pain was assessed using the visual analogue scale (VAS).Results: Hollow screw placement combined with PVP was successfully performed in all patients. The average operation time was 39.2± 5.1 min, and the average volume of bone cement injected was 5.85± 0.83mL. No leakage of bone cement into spinal canal occurred.The mean preoperative ODI score was 75.70± 4.39, but this decreased significantly postoperatively(P< 0.05), being 37.70± 6.95 at 1 day and 26.40± 4.90, 23.70± 4.87, 21.70± 5.46, and 20.50± 4.21 at 1, 3, 6, and 12 months after the operation, respectively. The mean VAS pain score before the operation was 8.35± 0.63, but the symptoms of back pain were significantly relieved after operation(P< 0.05). The mean VAS scores 1 day and 1, 3, 6, and 12 months after the operation were 3.45± 0.47, 2.55± 0.60, 1.89± 0.48, 1.50± 0.27, and 1.12± 0.20, respectively.Conclusion: Hollow screw placement combined with percutaneous vertebroplasty serves as a valuable three-column intensive treatment for patients with Kummell’s disease and pedicle rupture. This procedure has the advantages of minimal trauma, less pain and quick recovery. The strong anchoring of bone cement and hollow screws provides stable and firm healing conditions for vertebral and pedicle fractures.Keywords: three-column enhancement, PVP, hollow screw, Kummell’s disease, pedicle rupture

Liping Zou,1,&ast; Wanli Kang,2,&ast; Chunhui Guo,3,&ast; Juan Du,4,&ast; Qing Chen,1 Zhengyu Shi,1 Xianzhen Tang,1 Li Liang,1 Peijun Tang,5 Qing Pan,6 Qingdong Zhu,7 Song Yang,8 Zhanlin Chang,9 Zhouli Guo,1 Guihui Wu,1 Shenjie Tang2 1Department of Tuberculosis, Public Health Clinical Center of Chengdu, Chengdu, People’s Republic of China; 2Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 3Department of Tuberculosis, Harbin Chest Hospital, Harbin, People’s Republic of China; 4Department of Tuberculosis, Wuhan Pulmonary Hotel, Wuhan, People’s Republic of China; 5Department of Tuberculosis, the Fifth People’s Hospital of Suzhou, Suzhou, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Anqing Municipal Hospital, Anqing, People’s Republic of China; 7Department of Tuberculosis, the Fourth People’s Hospital of Nanning, Nanning, People’s Republic of China; 8General Internal Medicine Department, Chongqing Public Health Medical Center, Chongqing, People’s Republic of China; 9Department of Surgery, the Third People’s Hospital of Tibet Autonomous Region, Lasa, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guihui Wu, Department of Tuberculosis, Public Health Clinical Center of Chengdu, Jingjusi 18 Street, Jingjiang District, Chengdu, Sichuan, People’s Republic of China, Tel +86-28-8455-0573, Email wghwgh2584@sina.com Shenjie Tang, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, People’s Republic of China, Tel +86-13621028338, Email tangsj1106@vip.sina.comObjective: Rifampin-resistant tuberculosis (RR-TB) remains a serious global public health concern. We assessed treatment outcomes and associated influencing factors among RR-TB patients in China.Methods: This research enrolled 1339 patients who started RR-TB treatment between May 2018 and April 2020 in China retrospectively. Data were collected from the electronic medical records. Multivariable logistic regression analysis was used to identify the influencing factors related to unfavorable outcomes.Results: Of the 1339 RR-TB patients, 78.8% (1055/1339) achieved treatment success (cured or treatment completed), 5.1% (68/1339) experienced treatment failure, 1.1% (15/1339) died during treatment, 10.1% (135/1339) were lost to follow-up, and 4.9% (66/1339) were not evaluated. About 67.7% (907/1339) of patients experienced at least one adverse event (AE). The most common AE was hypohepatia (507/1339, 37.9%), followed by hyperuricemia (429/1339, 32.0%), anemia (368/1339, 27.5%), electrolyte disturbance (318/1339, 23.7%), peripheral neuritis (245/1339, 18.3%), and gastrointestinal reactions (203/1339, 15.2%). Multivariate analysis showed that age ≥ 60 years [adjusted odds ratio (aOR): 1.96, 95% confidence interval (CI): 1.39– 2.77], national minority (aOR: 2.36, 95% CI: 1.42– 3.93), smoking (aOR: 1.50, 95% CI: 1.10– 2.04), cardiopathy (aOR: 2.90, 95% CI: 1.33– 6.31), tumors (aOR: 9.84, 95% CI: 2.27– 42.67), immunocompromise (aOR: 2.17, 95% CI: 1.21– 3.91), re-treated TB (aOR: 1.46, 95% CI: 1.08– 1.97), and experienced gastrointestinal reactions (aOR: 2.27, 95% CI: 1.52– 3.40) were associated with unfavorable outcomes. Body mass index (BMI) ≥ 18.5 kg/m2, regimens containing bedaquiline and experienced adverse events (AEs) such as hypohepatia, leukopenia, peripheral neuritis, and optic neuritis were associated with favorable outcomes.Conclusion: High rates of treatment success were achieved for RR-TB patients at tertiary tuberculosis hospitals in China. Age ≥ 60 years, national minority, smoking status, comorbidities, re-treated TB, and experienced gastrointestinal reactions were independent prognostic factors for unfavorable treatment outcomes.Keywords: RR-TB, treatment outcomes, influencing factors, China

Gang Deng, Yuanyuan Yang, Song Lu, Lin Ma, Guohua Wu College of Biotechnology and Sericultural Research Institute, Jiangsu University of Science and Technology, Zhenjiang, 212100, People’s Republic of ChinaCorrespondence: Guohua Wu, Email ghwu@just.edu.cnIntroduction: With the development of technology, personal heat management has become a focus of attention. Phase change fabrics, as intelligent materials, are expected to be widely used in multiple fields, bringing comfortable, intelligent and convenient living experience.Methods: In this study, miniature phase change microcapsules (MPCM) with n-octadecane as core and poly(methyl methacrylate) as shell were successfully prepared. Using the in-situ reduction property of polydopamine, gold nanoparticles were deposited on the surface of the microcapsules, which retained the heat storage function and imparted photothermal and antibacterial properties. The MPCM with photothermal conversion function was modified on the surface of silk fabric using aqueous polyurethane after verified by comprehensive material characterisation techniques.Results: Under the near infrared light of 808 nm wavelength and 0.134 W/cm² irradiation intensity, the MPCM@PDA@Au modified silk fabrics showed excellent photothermal conversion performance, which could be increased from 25°C to 60°C in 50s. After the light source was cut off, the fabrics showed good heat release ability, with melting enthalpy and crystallisation enthalpy reaching 41.58 J/g and 43.3 J/g, respectively, which were not changed after repeated cycles. After the light source is cut off, the fabric has good heat release ability, and the enthalpy of melting and crystallisation reaches 41.58 J/g and 43.3 J/g, respectively, and the photothermal efficiency remains unchanged after many cycles of use, which proves that it has excellent durability and stability. The antimicrobial test shows that the fabric has significant antibacterial effect on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus).Discussion: MPCM@PDA@Au silk fabrics bring new possibilities for the future of personal thermal management and antimicrobial protection in the field of medical health, outdoor sports and other areas of broad application prospects, heralding the birth of a series of innovative applications and solutions.Keywords: photothermal conversion, phase change material, thermal energy storage, functional textile

Zhilin Zhang,1– 4 Aldrin D Calderon,2 Xingyu Huang,5 Guixian Wu,6 Chuanjian Liang1,3,4 1School of Physics and Telecommunications Engineering, Yulin Normal University, Yulin, People’s Republic of China; 2School of Mechanical, Manufacturing and Energy Engineering, Mapua University, Manila, Philippines; 3Center for Applied Mathematics of Guangxi, Yulin Normal University, Yulin, People’s Republic of China; 4Guangxi Universities Key Laboratory of Complex System Optimization and Big Data Processing, Yulin Normal University, Yulin, People’s Republic of China; 5School of Information Technology, Mapua University, Manila, Philippines; 6Yulin Health School of Guangxi Medical University, Yulin, People’s Republic of ChinaCorrespondence: Chuanjian Liang, Email lcj19@ylu.edu.cnPurpose: To address the application requirements of soft actuators in rehabilitation training gloves, and in combination with ergonomic requirements, we designed a segmented soft actuator with bending and elongation modules. This actuator can achieve independent or coupled movements of the finger joints.Methods: A finite element model of the joint actuator was established to compare the driving performance of actuators with different structural forms. Numerical calculations were used to analyze the effects of structural size parameters on the bending characteristics and end output force of the actuator. The design was then refined based on these analyses.Results: The joint actuator designed in this study demonstrated a 71% increase in bending angle compared to the standard fast pneumatic network structure. Key factors affecting the driving performance include the thickness of the constraint layer, the inner wall thickness of the chamber, chamber height, chamber width, chamber spacing, chamber length, and the number of chambers. After improvements, the bending angle of the joint actuator increased by 60.6%, and the output force increased by 145.9%, indicating significant improvement.Conclusion: This study designed and improved a soft actuator for hand rehabilitation training, achieving independent and coupled joint movements. The bending angle, bending shape, and joint driving force of the soft actuator meet the requirements for finger rehabilitation training.Keywords: rehabilitation training, soft actuators, fast pneumatic networks, structural optimization, finite element method

Jianqiang Liang,1,&ast; Weixiong Chen,2,&ast; Yanhui Zhou,3 Weijia Meng,3 Man Xie,3 Yunying Weng,1 Luxuan Qin,1 Jianmin Li,4 Guanyi Wu1,5,6 1College of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, People’s Republic of China; 2School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China; 3College of Pharmacology, Guangxi University of Chinese Medicine, Nanning, People’s Republic of China; 4Department of Dermatology, The Third Affiliated Hospital, Guangxi Medical University, Nanning, People’s Republic of China; 5Key Laboratory for Complementary and Alternative Medicine Experimental Animal Models of Guangxi, Nanning, People’s Republic of China; 6Guangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guanyi Wu, School of Basic Medicine, Guangxi University of Chinese Medicine, 13 Wu He Road, Nanning, Guangxi, 530299, People’s Republic of China, Email wugy@gxtcmu.edu.cnPurpose: This study seeks to investigate the effect of evodiamine on psoriasis and psoriatic pruritus.Methods: Imiquimod-induced psoriasiform dermatitis in mice was used as a model, and evodiamine was topically applied for seven days. The mice were observed daily for skin damage on the back, clinical score and their scratching behavior was recorded. Blood samples were collected on the final day of the experiment, and the serum levels of pruritus-associated inflammatory cytokines tumor necrosis factor (TNF) -α, interleukin (IL) − 23, and IL-17A were measured using enzyme-linked immunosorbent assay. Histopathological changes were observed in Hematoxylin and Eosin-stained skin specimens. The expression levels of transient receptor potential vanilloid (TRPV) 1, TRPV3, TRPV4, and the pruritus-related mediators Substance P (SP), nerve growth factor (NGF), and calcitonin gene-related peptide (CGRP) in the skin lesions were analyzed using Western blot and qRT-PCR. The effect of evodiamine on the exploratory behavior, motor, and coordination abilities of mice was assessed using open field, suspension, and Rota-Rod experiments. Molecular docking was utilized to verify the binding of evodiamine to the residues of TRPV1, TRPV3, and TRPV4.Results: Evodiamine reduced pruritus and inhibited inflammation by decreasing the levels of inflammatory mediators TNF-α, IL-23, and IL-17A in the serum of Imiquimod-induced mice and attenuated the mRNA and protein expression levels of SP, NGF, CGRP, TRPV1, TRPV3, and TRPV4 in the skin.Conclusion: Evodiamine is an effective treatment for psoriasis and pruritus, due to its ability to inhibit immune inflammation and pruritic mediators.Keywords: evodiamine, TRP channel, psoriasis

Xinyao Ding,1 Shujun Li,2 Xue Liu,2 Xiaowen Zhan,2 Zhiyuan Wang,2 Mengzhu Wang,2 Guannan Wu3 1Department of Paediatrics, Luohe Yancheng District People’s Hospital, Luohe, Henan, 462300, People’s Republic of China; 2Department of Pediatrics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, 453100, People’s Republic of China; 3Department of ICU, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, 453100, People’s Republic of ChinaCorrespondence: Shujun Li, Department of Pediatrics, The First Affiliated Hospital of Xinxiang Medical University, No. 88 of Jiankang road, Weihui, Henan, 453100, People’s Republic of China, Tel +8613781905766, Email ruolin2223@126.comObjective: This study explored the level of nuclear factor-ƙB (NF-ƙB) in the bronchoalveolar lavage fluid (BALF) of children with severe Mycoplasma Pneumoniae pneumonia (SMPP) and the correlation between NF-ƙB, cellular immunity, and clinical characteristics.Methods: A total of 41 hospitalized children diagnosed with SMPP were selected and included in the SMPP group, and 13 bronchial foreign bodies (FB) without infection during the same period were included in the FB group. The NF-ƙB in the BALF of participants was detected by enzyme-linked immunosorbent assay. The correlation between NF-ƙB and laboratory findings, cellular immunity, and the clinical features in children with SMPP was analyzed. The differences in chest imaging and bronchoscopy in children with SMPP were observed.Results: The levels of NF-ƙB were significantly increased in the SMPP group compared with the FB group (P < 0.001). There were correlations between different NF-ƙB pairs in the SMPP group (P < 0.01). Nuclear factor-ƙB (NF-ƙB) correlated with IL-6, the mycoplasma load in BALF, fever peak, length of hospital stay, and sputum suppository (P < 0.05). The higher the intracellular NF-ƙB level in BALF, the lower the CD3+ CD4+ value in peripheral blood (P < 0.05). Intracellular NF-ƙB and total NF-ƙB correlated with pleural effusion, pericardial effusion, and extrapulmonary complications (P < 0.05).Conclusion: NF-ƙB is involved in airway inflammation changes in children with SMPP. The higher the level of NF-ƙB in the airway, the more severe the clinical manifestations, and the longer the length of hospital stay is likely to be.Keywords: mycoplasma pneumoniae pneumonia, bronchoalveolar lavage fluid, NF-ƙB, cellular immunity, children

Chengzhang Yang,1,2,&ast; Weifang Liu,2,3,&ast; Zijia Tong,1,&ast; Fang Lei,3,4 Lijin Lin,2,3 Xuewei Huang,3,5 Xingyuan Zhang,3,6 Tao Sun,2,3 Gang Wu,1 Huajing Shan,1 Shaoze Chen,1 Hongliang Li2,3 1Department of Cardiology, Huanggang Central Hospital, Huanggang, People’s Republic of China; 2Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Institute of Model Animal, Wuhan University, Wuhan, People’s Republic of China; 4Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 5Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 6School of Basic Medical Science, Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongliang Li, Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China, Tel/Fax +86-27-68759302, Email lihl@whu.edu.cn Shaoze Chen, Department of Cardiology, Huanggang Central Hospital, Huanggang, People’s Republic of China, Tel/Fax +86-713-8381191, Email chenshaoze@hgyy.org.cnAim: The evidence on the association between insulin resistance (IR) and the prevalence or incidence of cardiac dysfunction has been controversial, and the relationship between pre-diabetic IR and cardiac function is lacking. Large sample studies in the Chinese general population are urgently needed to explore the association between IR and the risk of left ventricular hypertrophy (LVH) and decreased left ventricular diastolic function with preserved ejection fraction (LVDFpEF).Methods: Based on a National Health Check-up database in China, we conducted a multicenter cross-sectional retrospective study in 344,420 individuals. Furthermore, at a single center, we performed two retrospective longitudinal studies encompassing 8270 and 5827 individuals to investigate the association between IR and the development of new-onset LVH and LVDFpEF, respectively. The median follow-up duration exceeded 2.5 years. The triglyceride and glucose (TyG) index, known for its high sensitivity in detecting IR, serves as a reliable alternative marker of IR. The logistic and cox proportional hazard regression models were used to determine the relationships.Results: In the cross-sectional study, IR showed a positive association with the prevalence of LVH and decreased LVDFpEF after adjusting for confounders. In the longitudinal cohort, IR was also correlated with the new onset of LVH and decreased LVDFpEF, with hazard ratios (HR) of 1.986 (95% CI: 1.307, 3.017) and 1.386 (95% CI: 1.167, 1.647) in the fourth quartile of TyG levels compared to the lowest quartile, respectively, after adjusting for confounders. The subgroup analysis in non-hypertensive or non-diabetic people and the sensitivity analysis in the population with homeostasis model assessment of insulin resistance (HOMA-IR) further verified the above-mentioned results.Conclusion: IR was associated with LVH and decreased LVDFpEF. Effective management of IR may prevent or delay the development of adverse LVH and decreased LVDFpEF.Keywords: insulin resistance, triglyceride and glucose index, left ventricular hypertrophy, left ventricular diastolic function

Wenjin Zhang,1 Qiang Song,1 Xiaofei Bi,1 Wei Cui,1 Chengmei Fang,1 Jianya Gao,1 Jinan Li,1 Xiang Wang,1 Kai Qu,1 Xian Qin,1 Xuan An,2,3 Cheng Zhang,1,3 Xianxiang Zhang,1,3 Fang Yan,4 Guicheng Wu1– 3 1Chongqing Municipality Clinical Research Center for Endocrinology and Metabolic Diseases, Chongqing University Three Gorges Hospital, Chongqing, People’s Republic of China; 2Department of Hepatology, Chongqing University Three Gorges Hospital, Chongqing, People’s Republic of China; 3School of Medicine, Chongqing University, Chongqing, People’s Republic of China; 4Geriatric Diseases Institute of Chengdu, Department of Geriatrics, Chengdu Fifth People’s Hospital, Chengdu, People’s Republic of ChinaCorrespondence: Guicheng Wu, Chongqing University Three Gorges Hospital, Xincheng Road 165&num;, Wanzhou District, Chongqing, 404000, People’s Republic of China, Tel +(86) 58103079, Fax +86 23 581045783, Email wuguicheng@cqu.edu.cn Fang Yan, Geriatric Diseases Institute of Chengdu, Department of Geriatrics, Chengdu Fifth People’s Hospital, Mashi Street 33&num;, Wenjiang District, Chengdu, 611130, People’s Republic of China, Tel/Fax +86 28 82661127, Email fangyan@cdutcm.edu.cnPurpose: Pueraria lobata (P. lobata), a dual-purpose food and medicine, displays limited efficacy in alcohol detoxification and liver protection, with previous research primarily focused on puerarin in its dried roots. In this study, we investigated the potential effects and mechanisms of fresh P. lobata root-derived exosome-like nanovesicles (P-ELNs) for mitigating alcoholic intoxication, promoting alcohol metabolism effects and protecting the liver in C57BL/6J mice.Methods: We isolated P-ELNs from fresh P. lobata root using differential centrifugation and characterized them via transmission electron microscopy, nanoscale particle sizing, ζ potential analysis, and biochemical assays. In Acute Alcoholism (AAI) mice pre-treated with P-ELNs, we evaluated their effects on the timing and duration of the loss of the righting reflex (LORR), liver alcohol metabolism enzymes activity, liver and serum alcohol content, and ferroptosis-related markers.Results: P-ELNs, enriched in proteins, lipids, and small RNAs, exhibited an ideal size (150.7 ± 82.8 nm) and negative surface charge (− 31 mV). Pre-treatment with 10 mg/(kg.bw) P-ELNs in both male and female mice significantly prolonged ebriety time, shortened sobriety time, enhanced acetaldehyde dehydrogenase (ALDH) activity while concurrently inhibited alcohol dehydrogenase (ADH) activity, and reduced alcohol content in the liver and serum. Notably, P-ELNs demonstrated more efficacy compared to P-ELNs supernatant fluid (abundant puerarin content), suggesting alternative active components beyond puerarin. Additionally, P-ELNs prevented ferroptosis by inhibiting the reduction of glutathione peroxidase 4 (GPX4) and reduced glutathione (GSH), and suppressing acyl-CoA synthetase long-chain family member 4 (ACSL4) elevation, thereby mitigating pathological liver lipid accumulation.Conclusion: P-ELNs exhibit distinct exosomal characteristics and effectively alleviate alcoholic intoxication, improve alcohol metabolism, suppress ferroptosis, and protect the liver from alcoholic injury. Consequently, P-ELNs hold promise as a therapeutic agent for detoxification, sobriety promotion, and prevention of alcoholic liver injury.Keywords: Pueraria lobata root-derived exosome-like nanovesicles, acute alcoholism, loss of the righting reflex, ethanol metabolism, ferroptosis

Nengwen Wu,&ast; Xiaoqing Shen,&ast; Jianwei Li, Miaolian Chen, Guishen Wu, Haiming Niu, Hongkai Liang, Ting Yang Department of Critical Care Medicine, Zhongshan People’s Hospital, Zhongshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongkai Liang; Ting Yang, Department of Critical Care Medicine, Zhongshan People’s Hospital, Zhongshan, 528400, People’s Republic of China, Email 1019978382@qq.com; 53103334@qq.comAbstract: Septic cardiomyopathy (SCM) is often associated with bacterial infections but also occurs with infections with viruses such as influenza and spirochetes, including syphilis. However, there has been no systematic investigation into whether Aspergillus infections can cause septic cardiomyopathy. We report on such a case for the first time in a patient without immunodeficiency. Therefore, clinicians should be concerned with septic cardiomyopathy caused by some atypical or rare pathogens when admitting such patients.Keywords: septic cardiomyopathy, aspergillus, extracorporeal membrane oxygenation, metagenomic next-generation sequencing

Zetan Chen,1,2 Gang Wu,2 Xiangying Lin,2 Xiaopeng Huang,2 Shuai Zhang,2 Kaihua Chen,1 Zhongguo Liang,1 Xiaodong Zhu1,3,4 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Radiation Oncology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People’s Republic of China; 3Department of Oncology, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of China; 4Key Laboratory of Early Prevention and Treatment for Regional High-Incidence-Tumor, Guangxi Medical University, Ministry of Education, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Xiaodong Zhu, Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86-13978873616, Email zhuxdonggxmu@126.comPurpose: Elevated serum sialic acid (SA) is one of the indicators of poor prognosis in various malignant tumors. This study intends to determine the relationship between serum SA levels and survival prognosis in nasopharyngeal carcinoma (NPC).Patients and Methods: From 2014 to 2016, NPC patients with no distance metastasis undergoing intensity-modulated radiotherapy (IMRT) were retrospectively analyzed. The serum SA levels before initial treatment were measured, and an optimal cut-off level was determined by X-tile software. A propensity score matching (PSM) technique was applied to reduce intergroup differences between the low serum SA level group and the high serum SA level group. Chi-square tests were utilized for comparing intergroup differences, Kaplan-Meier approach was utilized for plotting survival curves, and univariate and multivariate Cox proportional hazards regression models were employed for analyzing prognostic factors.Results: Overall, 293 NPC patients with no distance metastasis were included. The optimal cut-off level of serum SA was 65.10 mg/dl. The baseline levels after PSM were more balanced compared to those before PSM. Survival analysis showed that the locoregional relapse-free survival (LRRFS, p=0.010), distant metastasis–free survival (DMFS, p=0.014), progression-free survival (PFS, p=0.009), and overall survival (OS, p=0.015) survival curves of the low serum SA level group and high serum SA level group were statistically significant differences. Univariate analysis showed that American Joint Committee on Cancer (AJCC) stage, T stage, N stage, neoadjuvant chemotherapy (NC), and serum SA expression level were factors influencing the prognosis of NPC patients. Multivariate analysis showed that high serum SA expression level was related to worse PFS and OS in NPC patients with no distance metastasis.Conclusion: High serum SA level (SA > 65.10 mg/dl) before treatment is associated to poor survival outcomes in NPC and is an independent adverse prognostic factor in NPC patients with no distance metastasis.Keywords: serum sialic acid, nasopharyngeal carcinoma, prognosis, propensity score matching

Guitao Wu, Xi Lin, Hua Jiang, Zhenyin Liu Department of Interventional Radiology and Vascular Anomalies, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510623, People’s Republic of ChinaCorrespondence: Zhenyin Liu, Department of Interventional Radiology and Vascular Anomalies, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, Guangdong, 510623, People’s Republic of China, Email zhenyin@gwcmc.orgBackground: Venous malformation is related to genes and results in functional and morphologic anomalies. Genetic variations affecting the development of vessel endothelial cells are unclear. Therefore, this study aimed to investigate the potential value of the miR-100 rs1834306 A>G polymorphism as a marker of susceptibility to venous malformation.Methods: In this case–control study in southern Chinese children, we collected blood samples from 1158 controls and 1113 patients with venous malformation. TaqMan genotyping of miR-100 rs1834306 A>G was performed by real-time fluorescent quantitative polymerase chain reaction.Results: Multivariate logistic regression analysis showed that there was no significant association between the presence of the miR-100 rs1834306 A>G polymorphism and susceptibility to venous malformation by evaluating the values of pooled odds ratios and 95% confidence intervals. Similarly, among different sites, rs1834306 A>G was also not associated with venous malformation.Conclusion: Our results suggest that the miR-100 rs1834306 A>G polymorphism is not associated with susceptibility to venous malformation in southern Chinese children. These results need to be further confirmed by investigating a more diverse ethnic population of patients with venous malformations.Keywords: vascular malformation, susceptibility, miR-100, polymorphism

Wan Tang,1,2 Hongdou Chen,1,2 Zixin Zhang,1,2 Gang Wu,1,2 Yanquan Lin1– 3 1Pharmacy, Suqian Hospital of Nanjing Drum-Tower Hospital Group, Suqian, People’s Republic of China; 2Pharmacy, Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, People’s Republic of China; 3Pharmacy, Xuzhou Medical University, Xuzhou, People’s Republic of ChinaCorrespondence: Hongdou Chen, Email chenhongdou2000@aliyun.comObjective: To analyse the relationship between the adverse drug reactions (ADRs) of essential drugs and visits, based on the recorded annual increase in ADRs associated with essential medicines in China, to provide a reliable theoretical basis for further analysis and optimization of the safety of essential drugs.Methods: The data of adverse reactions of essential drugs in China from 2011 to 2020, time series analysis was conducted, and vector autoregressive (VAR) model was established. The relationship between the number of ADRs and visits was explored empirically through Granger causality test, impulse response function and variance decomposition.Results: There was a long-term cointegration relationship and one-way causality between the number of visits and ADRs caused by essential medicines. In the initial stage, the ADR response to the number of visits increased sharply, but with an increase in the number of lag periods, the impact remained basically stable, even showing a slight decreasing trend.Conclusion: The number of visits impacts ADRs caused by essential medicines, but this impact remains basically stable after reaching a certain level.Keywords: essential medicines, adverse drug reactions, vector autoregressive model, time-series analysis

Hongfeng Chen,1 Zhen Li,1 Xiaoqi Li,1 Jiongjiong Lu,1 Beibei Chen,1 Qiongchao Wang,1 Guangliang Wu2 1Department of Foot and Ankle Surgery, The Second Affiliated Hospital of Luohe Medical College, Luohe, Henan, 462300, People’s Republic of China; 2Department of Orthopaedics, The Second Affiliated Hospital of Luohe Medical College, Luohe, Henan, 462300, People’s Republic of ChinaCorrespondence: Guangliang Wu, Department of Orthopaedics, The Second Affiliated Hospital of Luohe Medical College, Western Haihe Road, Luohe, Henan, 462300, People’s Republic of China, Email wuguangliang6@sina.comAbstract: Gene therapy has emerged as a promising and innovative approach in cartilage regeneration. Integrating biomaterials into gene therapy offers a unique opportunity to enhance gene delivery efficiency, optimize gene expression dynamics, modulate immune responses, and promote tissue regeneration. Despite the rapid progress in biomaterial-based gene delivery, there remains a deficiency of comprehensive discussions on recent advances and their specific application in cartilage regeneration. Therefore, this review aims to provide a thorough overview of various categories of biomaterials employed in gene delivery, including both viral and non-viral vectors, with discussing their distinct advantages and limitations. Furthermore, the diverse strategies employed in gene therapy are discussed and summarized, such as the utilization of growth factors, anti-inflammatory cytokines, and chondrogenic genes. Additionally, we highlights the significant challenges that hinder biomaterial-based gene delivery in cartilage regeneration, including immune response modulation, gene delivery efficiency, and the sustainability of long-term gene expression. By elucidating the functional properties of biomaterials-based gene therapy and their pivotal roles in cartilage regeneration, this review aims to enhance further advances in the design of sophisticated gene delivery systems for improved cartilage regeneration outcomes.Keywords: cartilage, regeneration, delivery systems, biomaterials, osteoarthritis

Song Lyu,1 Guobin Wu,2 Yingfen Wu1 1Department of Anesthesiology, The Second Affiliated Hospital of Hainan Medical University, Haikou, People’s Republic of China; 2Medical Record Management Department, The Second Affiliated Hospital of Hainan Medical University, Haikou, People’s Republic of ChinaCorrespondence: Song Lyu, Department of Anesthesiology, The Second Affiliated Hospital of Hainan Medical University, Haikou, People’s Republic of China, Fax +8689866808208, Email Lssjk1@126.comObjective: To investigate the potential relationship between the prone jackknife position during percutaneous nephroscopy and the occurrence of intraoperative hypotension.Methods: A retrospective analysis was conducted on 651 patients who underwent percutaneous nephroscopy at the Second Affiliated Hospital of Hainan Medical University. The primary focus was to investigate the occurrence of hypotension during the surgical procedure and assess the duration of hypotensive episodes. Patients were categorized into the prone jackknife position group and the lateral position group. To compare the incidence of intraoperative hypotension between the two groups, a 1:1 propensity match was performed. Following the matching process, intraoperative hypotension was assessed and compared between the two groups before and after the match. The binary logistic regression analysis determined the probability of intraoperative hypotension occurred in each group. Furthermore, linear regression analysis was used to analyze the duration of hypotensive episodes experienced by patients in both groups.Results: After propensity score matching, a total of 272 patients with similar characteristics were obtained (136 in each group). The prone jackknife group had a significantly higher incidence of intraoperative hypotension than the lateral group after the match, with an odds ratio of 2.71 (95% confidence interval: 1.595– 4.605). Binary logistic regression analysis showed that age and body position exhibited statistical significance as risk factors. Linear regression analysis before and after the match indicated that the duration of hypotension was associated with age, surgical time, and a history of hypertension.Conclusion: The prone jackknife position syndrome after general anesthesia could occur in surgeries. The position could contribute to the development of hypotension during the percutaneous nephroscopy procedure.Keywords: prone, jackknife position, percutaneous nephroscopy, intraoperative hypotension

Xueping Yang,1,2,&ast; Changhong Guo,3,&ast; Guangjie Wu,1,&ast; Kai Zhao,4 Dong Xiang,1 Dong Xu,5 Dong Liu,1 Yan He1 1Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Pharmacy, Jingzhou Hospital of Traditional Chinese Medicine, Jingzhou, 434000, People’s Republic of China; 3Department of Scientific Education, Jingzhou Hospital of Traditional Chinese Medicine, Jingzhou, 434000, People’s Republic of China; 4Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 5Department of Infection Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan He; Dong Liu, Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Email heyan_may@hotmail.com; ld2069@outlook.comPurpose: Due to the spread of antimicrobial-resistant bacteria and poor penetration of many antimicrobial drugs across the blood–brain barrier following intravenous administration, treatment of central nervous system (CNS) infections is challenging, especially infections caused by carbapenem-resistant organisms (CRO). Intraventricular (IVT) infusion of antimicrobial drugs could be a choice. This report aims to describe a patient with CNS infection caused by carbapenem-resistant Acinetobacter baumannii (CRAB) which was successfully treated with IVT combined with intravenous (IV) colistin sulfate.Methods: A case of CNS infection caused by CRAB after a craniocerebral injury was presented. The patient was treated with IVT together with IV colistin sulfate. Moreover, literature on the regimens and safety of colistin sulfate were also reviewed and summarized.Results: Intraventricular (50,000 U, qd/100,000 U, qd) combined with IV (500,000 U, q12h/500,000 U, q8h) colistin sulfate was given to the patient, and the CNS infection was successfully controlled. The patient was finally transferred back to a local hospital for rehabilitation treatment. No nephrotoxicity or neurotoxicity was observed during the therapy.Conclusion: IV combined with IVT colistin sulfate is effective in the treatment of CNS infections caused by CRAB. IVT concomitant IV colistin sulfate might be a therapeutic option worth considering in the treatment of CNS infections caused by CRO.Keywords: central nervous system infection, Acinetobacter baumannii, intraventricular administration, colistin sulfate, colistin, polymyxin

Xiaoqing Shen,&ast; Hongkai Liang,&ast; Guishen Wu, Miaolian Chen, Jianwei Li Department of Critical Care Medicine, Zhongshan People’s Hospital, Zhongshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianwei Li, Department of Critical Care Medicine, Zhongshan People’s Hospital, Zhongshan, 528400, People’s Republic of China, Email lijwprof2005@163.comAbstract: Streptococcus dysgalactiae subspecies equlsimilis (SDSE) is considered an important bacterial pathogen, and attention has also increased with the increasing number of invasive SDSE infections. Here, we report a patient with S. dysgalactiae toxic shock syndrome complicated by symmetrical peripheral gangrene (SPG). Despite surviving active treatment, amputation severely impacts the quality of life of patients. Therefore, we should pay attention to the early treatment of SDSE infection and the prevention and treatment of related complications.Keywords: Streptococcus dysgalactiae subspecies equlsimilis, streptococcal poisoning shock syndrome, symmetric peripheral gangrene

Juanzi Zeng,1,2 Wenwei Fan,3 Jiaquan Li,1,2 Guowu Wu,1,2 Heming Wu2 1Department of Medical Oncology, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Center for Precision Medicine, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 3Department of Gastroenterology, Dongguan Eighth People’s Hospital, Dongguan, People’s Republic of ChinaCorrespondence: Heming Wu, Center for Precision Medicine, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, No. 63 Huangtang Road, Meijiang District, Meizhou, People’s Republic of China, Email wuheming1986@126.comBackground: The occurrence, progression, and prognosis of colorectal cancer (CRC) are regulated by EGFR-mediated signaling pathways. However, the relationship between the core genes (KRAS/NRAS/BRAF/PIK3CA) status in the signaling pathways and clinicopathological characteristics of CRC patients in Hakka population remains controversial.Methods: Patients were genotyped for KRAS (codons 12, 13, 61, 117, and 146), NRAS (codons 12, 61, 117, and 146), BRAF (codons 600), and PIK3CA (codons 542, 545 and 1047) mutations. Clinical records were collected, and clinicopathological characteristic associations were analyzed together with mutations of studied genes.Results: Four hundred and eight patients (256 men and 152 women) were included in the analysis. At least one mutation in the four genes was detected in 216 (52.9%) patients, while none was detected in 192 (47.1%) patients. KRAS, NRAS, BRAF, and PIK3CA mutation status were detected in 190 (46.6%), 11 (2.7%), 10 (2.5%), 34 (8.3%) samples, respectively. KRAS exon 2 had the highest proportion (62.5%). Age, tumor site, tumor size, lymphovascular invasion, and perineural invasion were not associated with gene mutations. KRAS mutations (adjusted OR 1.675, 95% CI 1.017– 2.760, P=0.043) and NRAS mutations (adjusted OR 5.183, 95% CI 1.239– 21.687, P=0.024) appeared more frequently in patients with distant metastasis. BRAF mutations (adjusted OR 7.224, 95% CI 1.356– 38.488, P=0.021) and PIK3CA mutations (adjusted OR 3.811, 95% CI 1.268– 11.455, P=0.017) associated with poorly differentiated tumor.Conclusion: KRAS/NRAS mutations are associated with distant metastasis and BRAF/PIK3CA mutations are associated with poor tumor differentiation in CRC. And the results provided a better understanding between clinicopathological characteristics and gene mutations in CRC patients.Keywords: colorectal cancer, KRAS, NRAS, BRAF, PIK3CA, clinicopathological feature

Yehong Liu,1,&ast; Jie Liu,1,&ast; Longqun Liu,2,&ast; Shaoqing Cao,1,3 Tianhui Jin,1 Liang Chen,1,3 Gangyong Wu,1,3 Gangjun Zong1,3 1Department of Cardiology, The 904th Hospital of Joint Logistic Support Force of PLA, Wuxi, Jiangsu, People’s Republic of China; 2Department of Respirology, The 904th Hospital of Joint Logistic Support Force of PLA, Wuxi, Jiangsu, People’s Republic of China; 3Department of Cardiology, Wuxi Clinical College of Anhui Medical University, Wuxi, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gangyong Wu; Gangjun Zong, Email wuwangyi520@sina.com; zonggj@163.comAim: Reducing the high morbidity and mortality of ST-segment elevation myocardial infarction (STEMI) and improving patient prognosis remains a major global challenge. This study aimed to explore whether dynamic fluctuations in biomarkers are valuable predictors of prognosis in patients with STEMI.Methods: This study included 216 patients with STEMI. Blood routine tests were performed on admission, 12 h after percutaneous coronary intervention (PCI), and at discharge. Systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), and pan-immune-inflammation-value (PIV) serum immune-inflammatory markers were calculated. The Cox proportional hazard model was used to assess the factors independently associated with the prognosis of STEMI. The optimal cutoff values for the inflammatory markers were calculated.Results: Eighty-five (39.35%) of the 216 patients had major adverse cardiovascular events (MACEs) during the 1-year follow-up. Most were male (81.18%) with a median age of 64 years (interquartile, 55– 69.5). Killip class ≥ II on admission (hazard ratio [HR], 1.859; 95% CI, 1.169– 2.957; P = 0.009), total stent length (HR, 1.016; 95% CI, 1.003– 1.029; P = 0.019), values of SIRI at 12 h after PCI (HR, 1.079; 95% CI, 1.050– 1.108; P < 0.001), and the Gensini score (HR, 1.014; 95% CI, 1.007– 1.022; P < 0.001) were independently associated with an increased risk of MACEs. Compared with SII, SIRI and PIV calculated at various time points and dynamically fluctuating changes, SIRI (cutoff value, 4.15; 95% CI, 0.701– 0.819; P < 0.001) and PIV (cutoff value, 622.71; 95% CI, 0.674– 0.796; P < 0.001) at 12 h after PCI showed the best efficacy for the prognosis of STEMI.Conclusion: Our study provides relevant evidence to the notion that SIRI or PIV at 12 h after PCI may be more accurate and economical predictors of long-term adverse prognosis in patients with STEMI.Keywords: systemic inflammatory response index, pan-immune-inflammation-value, ST-segment elevation myocardial infarction, major adverse cardiovascular events, prognosis, percutaneous coronary intervention

Guanghao Wu,1,&ast; Guanye Yu,2,&ast; Meiling Zheng,3,&ast; Wenhui Peng,2 Lei Li4 1School of Materials Science and Engineering, Beijing Institute of Technology, Beijing, 100081, People’s Republic of China; 2Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University, School of Medicine, Shanghai, 200072, People’s Republic of China; 3Dongzhimen Hospital Beijing University of Chinese Medicine, Beijing, 101121, People’s Republic of China; 4National Clinical Research Center for Obstetric & Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Li, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuai Fu Yuan, Eastern District, Beijing, 100730, People’s Republic of China, Tel +8613426328126, Fax +86 10 69158100, Email lilei64@pumch.cn Guanghao Wu, School of Materials Science and Engineering, Beijing Institute of Technology, Beijing, 100081, People’s Republic of China, Email bitwgh@126.comAbstract: Atherosclerosis (AS) is a chronic inflammatory disease, which may lead to high morbidity and mortality. Currently, the clinical treatment strategy for AS is administering drugs and performing surgery. However, advanced therapy strategies are urgently required because of the deficient therapeutic effects of current managements. Increased number of energy conversion-based organic or inorganic materials has been used in cancer and other major disease treatments, bringing hope to patients with the development of nanomedicine and materials. These treatment strategies employ specific nanomaterials with specific own physiochemical properties (external stimuli: light or ultrasound) to promote foam cell apoptosis and cholesterol efflux. Based on the pathological characteristics of vulnerable plaques, energy conversion-based nano-therapy has attracted increasing attention in the field of anti-atherosclerosis. Therefore, this review focuses on recent advances in energy conversion-based treatments. In addition to summarizing the therapeutic effects of various techniques, the regulated pathological processes are highlighted. Finally, the challenges and prospects for further development of dynamic treatment for AS are discussed.Keywords: atherosclerosis, nanomaterial, physiochemical, reactive oxygen species, energy conversion, therapy

Guolan Wu,1– 3 Huili Zhou,1,2 Duo Lv,1,2 Ruling Zheng,4 Lihua Wu,1 Songxia Yu,1,2 Jiejing Kai,1,2 Nana Xu,1,2 Lie Gu,5 Nanfang Hong,5 Jianzhong Shentu1,2 1Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Polytechnic Institute, Zhejiang University, Hangzhou, People’s Republic of China; 4The Fifth Affiliated Hospital, College of Medicine, Guangzhou Medical University, Guangzhou, People’s Republic of China; 5Hainan Honz Pharmaceutical Co. Ltd, Haikou, Hainan, People’s Republic of ChinaCorrespondence: Jianzhong Shentu, Email stjz@zju.edu.cnPurpose: Suramin is a multifunctional molecule with a wide range of potential applications, including parasitic and viral diseases, as well as cancer.Methods: A double-blinded, randomized, placebo-controlled single ascending dose study was conducted to investigate the safety, tolerability, and pharmacokinetics of suramin in healthy Chinese volunteers. A total of 36 healthy subjects were enrolled. All doses of suramin sodium and placebo were administered as a 30-minute infusion. Blood and urine samples were collected at the designated time points for pharmacokinetic analysis. Safety was assessed by clinical examinations and adverse events.Results: After a single dose, suramin maximum plasma concentration (Cmax) and area under the plasma concentration–time curve from time zero to the time of the last measurable concentration (AUClast) increased in a dose-proportional manner. The plasma half-life (t1/2) was dose-independent, average 48 days (range 28– 105 days). The cumulative percentages of the dose excreted in urine over 7 days were less than 4%. Suramin can be detected in urine samples for longer periods (more than 140 days following infusion). Suramin was generally well tolerated. Treatment-emergent adverse events (TEAEs) were generally mild in severity.Conclusion: The PK and safety profiles of suramin in Chinese subjects indicated that 10 mg/kg or 15 mg/kg could be an appropriate dose in a future multiple-dose study.Keywords: suramin, clinical pharmacokinetics, antiviral, safety, drug repurposing

Min Zhu,1 Yuyu Sun,1 Huawei Xue,1 Gang Wu,1 Zhen Wang,1 Junfeng Shi,1 Jiye Ma,1 Baorong Gu,1 Xiaoling Yan2 1Department of Spine Surgery, Nantong Third People’s Hospital, Affiliated Nantong Hospital 3 of Nantong University, Nantong, People’s Republic of China; 2Department of Chemotherapy, Affiliated Hospital of Nantong University, Nantong, People’s Republic of ChinaCorrespondence: Xiaoling Yan, Department of Chemotherapy, Affiliated Hospital of Nantong University, Nantong, 226001, People’s Republic of China, Email 5200007@ntu.edu.cnBackground: Osteosarcoma is a malignant tumor originating from the skeletal system. There is no effective treatment other than surgery and chemotherapy, which seriously endangers the health of children and adolescents. NEK6 is a novel discovered Serine/Threonine protein kinase that can regulate cell cycle and activate several oncogenic pathways.Methods: NEK6 expression in pan-cancer including sarcoma was evaluated using analysis tools of TIMER, UALCNA and GEPIA with TCGA database, and its association with overall survival in patients with sarcoma was also analyzed. TargetScan, tarbase, microT-CDS and Starbase online software were used to predict NEK6-targeted miRNAs, including miR-26a-5p. Tumor tissues from patients with osteosarcoma were collected for NEK6 and miRNA detection using RT-qPCR. NEK6 down-regulated by siRNAs or miR-26a-5p in osteosarcoma cells was detected by RT-qPCR, Western blot and Immunofluorescence staining assays. Effects of NEK6 knockdown on proliferation, migration, invasion and apoptosis of osteosarcoma cells were detected by CCK-8, wound healing, transwell and flow cytometry, respectively. The expressions of STAT3, metastasis and apoptosis-related genes were detected by Western blot.Results: High expression of NEK6 and low expression of miR-26a-5p were lowly expressed in osteosarcoma and they were negative correlation. NEK6 has been confirmed as a direct target for miR-26a-5p. In addition, NEK6 down-regulated by siRNAs or miR-26a-5p led to inhibition of cell proliferation, migration and invasion while promoting cell apoptosis. The levels of phosphorylated STAT3 and metastasis genes (MMP-2, MMP-9) were inhibited, while apoptotic gene Bax was promoted and Bcl2 was inhibited by miR-26a-5p upregulation.Conclusion: NEK6 can promote osteosarcoma progression via activating STAT3 signaling pathway, which is inhibited by miR-26a-5p, suggesting that NEK6 is a potential oncogene and miR-26a-5p is a suppressor of osteosarcoma. The strategy of inhibiting of NEK6 by miR-26a-5p may be an effective approach for osteosarcoma therapy.Keywords: osteosarcoma, NEK6, miR-26a-5p, STAT3 signaling pathway

Libin Liu,1,2,&ast; Guihua Wu,1,2 Jing Wang,1,2 Lijun Peng,1,2 Xiaoqun Xu,1,2 Long Cai1,2,&ast; 1Centre of Laboratory Medicine, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Centre of Laboratory Medicine, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Long Cai, Centre of Laboratory Medicine, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, No. 208 East Huancheng Road, Hangzhou, 310003, People’s Republic of China, Email cailong317@hotmail.comPurpose: Exploring whether smoking is an influencing factor for the inconsistency between QuantiFERONTB Gold assay (QFT-GIT) and tuberculosis etiology.Patients and Methods: The clinical data of patients who were confirmed positive for Mycobacterium tuberculosis (MTB) after undergoing QFT-GIT testing from September 2017 to August 2021 were retrospectively analyzed. Chi-square and rank-sum tests were used to compare the differences in characteristics between smokers and non-smokers. Logistic regression was used to adjust for confounding factors affecting smoking. Propensity score matching (PSM) was used to verify the above conclusions again.Results: Positive results of tuberculosis etiology were adopted as the standard, the incidence of inconsistent results between QFT-GIT and tuberculosis etiology was 8.90% (108/1213), of which the false negative rate was 6.27% (76/1213) and the indeterminate rate was 2.64% (32/1213). In the overall population, the smokers had a lower level of basal IFN-γ (Z=− 2.079, P=0.038). Among 382 elderly (≥ 65 years old) patients, the smokers had lower levels of antigen-stimulated IFN-γ (Z=− 2.838, P=0.005). After performing BOX-COX transformation on all non-normally distributed data, logistic stepwise regression was used to adjust confounding factors. The results showed that smoking was an influencing factor for the inconsistency between QFT-GIT and tuberculosis etiology results (OR=1.69, P=0.020). Using PSM for 1:2 matching, the results showed that smoking was still an independent risk factor for the inconsistent results of QFT-GIT and tuberculosis etiology (OR= 1.95, P=0.019). Age-stratified analysis showed that smoking was an independent risk factor in discordance between QFT-GIT and tuberculosis etiology in patients aged ≥ 65 years (OR=2.40, P=0.005), but not in patients aged < 65 years (P > 0.05).Conclusion: Smoking can reduce the body’s IFN-γ release ability, and smoking (especially the elderly) is an influencing factor for the inconsistency between QFT-GIT and tuberculosis etiological results.Keywords: tuberculosis etiology, PSM, inconsistency, influencing factors

Pengcheng Ma,1 Yadi Li,2 Yusen Feng,1 Gang Wu,3 Bin Li,4 Haiyan Wu5 1Department of Radiology, Kunming Yan ‘an Hospital, Kunming, 650000, People’s Republic of China; 2Department of Ophthalmology, Affiliated Hospital of Yunnan University, Kunming, 650000, People’s Republic of China; 3Department of Neurology, Kunming Yan ‘an Hospital, Kunming, 650000, People’s Republic of China; 4Department of Neurosurgery, Kunming Yan ‘an Hospital, Kunming, 650000, People’s Republic of China; 5Department of Cardiovascular, Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650000, People’s Republic of ChinaCorrespondence: Gang Wu, Tel/Fax +86 0871 632111408, Email yngangwu1126@126.comPurpose: To evaluate the stability of unruptured intracranial aneurysm (UIA) with high-resolution magnetic resonance imaging of the vessel wall (HR-VWI).Materials and Methods: A total of 92 UIA patients were enrolled. After MRA, HR-VWI imaging, the reconstruction of volume rendering (VR) and maximum intensity projection (MIP) were performed to observe the location and size of aneurysms, AR value (ratio of aneurysm height to aneurysmal diameter), SR value (ratio of maximum tumor depth to proximal parent artery diameter), and signal intensity were measured.Results: There were 7 aneurysms with UIA located in the anterior cerebral artery, 31 aneurysms with UIA in the middle cerebral artery, 1 aneurysm with UIA in the posterior cerebral artery, 18 aneurysms with UIA in the anterior communication, 5 aneurysms with UIA in the posterior communication, 34 aneurysms with UIA in the intracranial segment of the internal carotid artery and 3 aneurysms with UIA in the vertebral artery. Among them, 8 patients had more than two multiple aneurysms. The lesion size was 2– 38mm (6.3 ± 5.09). There are 46 aneurysms with wall enhancement: the maximum SR value was 7.03 and the minimum 1.2, and the maximum AR value was 7.5 and the minimum 1.0. Fifty-five aneurysms showed no enhancement of the tumor wall. The maximum SR value was 4.55 and the minimum 0.58, and the maximum AR value was 4.0 and the minimum 0.6, respectively. Patients were divided into a stable group and an unstable group according to the aneurysm wall. The enhancement rate, SR value, and AR value in the stable aneurysm group were significantly lower than those in the unstable aneurysm group (P < 0.05).Conclusion: MRA and HR-VWI can objectively reflect the stability of aneurysms by judging the morphology, SR value, and signal enhancement of UIA, and can provide a certain basis for diagnosis and treatment, which has become routine examination.Keywords: high-resolution magnetic resonance imaging of the vessel wall, unruptured intracranial aneurysm, signal intensity, enhancement, diagnosis

YuJing Wu,1,&ast; Sumei Wang,1,&ast; Guangye Wu,2 Jiandong Zhang,1 Shuye Liu1 1The Third Central Hospital of Tianjin, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin, People’s Republic of China; 2Second Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin Traditional Chinese Medicine Rehabilitation Center, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuye Liu, Tel +86-022-84112332, Fax +86 022-24384350, Email liushuye@tmu.edu.cnBackground: Brachybacterium muris is a species of Gram positive and strictly aerobic bacterium. It was first reported in 2003 after being isolated from the liver of a laboratory mouse strain. It was also found on human skin and nasal cavity. Herein, we present the first case pleural effusion infection in humans caused by Brachybacterium muris.Case Presentation: A 65-year-old man was admitted to our hospital for a 4-week history of fever, accompanied by chills, occasional abdominal pain, occasional chest tightness and shortness of breath. On the day of hospitalization, thoracentesis was performed and 1000mL of yellow cloudy fluid was released. Result of pleural fluid culture was positive and B. muris was identified using 16S rDNA amplification and sequence comparisons.Conclusion: To our knowledge, this is the first report of pleural effusion infection caused by B. muris. B. muris can be pathogenic in humans.Keywords: Brachybacterium muris, pleural effusion, infection

Xiulian Wu, Xin Wang, Huimin Guo, Lili Zhang, Guangjiang Wu Department of Nursing, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Xin Wang, Department of Nursing, Beijing Youan Hospital, Capital Medical University, No. 8, You an Men Outer Street, Fengtai District, Beijing, 100069, People’s Republic of China, Tel +86-13521101275, Email Wx220929@163.comObjective: To explore the application effect of the (software factors, hardware factors, environmental factors, parties and other factors, SHEL) model in respiratory tract exposure protection of staff in temporary COVID-19 hospitals.Methods: 207 Staff members working in the isolation units of Fangcang shelter hospitals between 20 May 2022 and 5 June 2022 were selected as research subjects. The SHEL model was used to protect and manage the respiratory exposure of the isolation unit staff to the novel coronavirus. The incidence of respiratory exposure among the staff in the isolation units was compared before the SHEL model’s implementation (20 May 2022– 28 May 2022) and afterwards the SHEL model’s implementation (29 May 2022– 5 June 2022).Results: Before the implementation of the SHEL model, a total of nine cases (4.35%) from 207 workers had respiratory exposure. Occurrence location: six cases in the isolation room (one-out room, level-one protection zone) and three cases in the drop-off area for patients outside the ward. After implementation, a total of two cases (0.97%) of respiratory tract exposure occurred among the 207 staff members; both occurred in the unprotected zone (two-out room, level-two protection zone), and the difference was statistically significant before and after the implementation (P < 0.05).Conclusion: New coronary pneumonia Fangcang shelter hospitals should use the SHEL model to manage the respiratory exposure of their isolation unit staff to reduce the respiratory exposure risk to staff in isolation units.Keywords: SHEL model, new coronavirus, makeshift hospital, respiratory tract exposure, protection management

During the continuous casting process, the residual oxygen in the tundish can be significantly reduced by argon blowing from the tundish cover (ABTC). As a result, the effect of protective casting can be obviously improved, which helps to reduce the reoxidation of molten steel in the tundish. In the present work, numerical models for the ABTC of a six-strand continuous casting machine were established and verified by the measured oxygen mass fraction in the tundish during the ABTC. The results indicate that the best conditions for ABTC are to install the argon pipes on either side of the tundish cover holes, seal the baking holes, and keep the stopper rod holes open. The argon flow rate should be ≥120 m3/h during the period of empty tundish and ≥60 m3/h during the period of normal casting. Based on the calculation results, industrial testsof ABTC were carried out. The results indicated that the increased nitrogen content in steel(Δw[N]) decreased by 21.5% from 8.78×10- 6 to 6.89×10-6 , from the end of RH to tundish, and the amount of inclusions except for MnS in bloom (scanned size: 8 mm × 8 mm) decreased by 21.3% from 13.43 to 10.57, and the average size of inclusions decreased by 19.0% from 9.27 μm to 7.51 μm.

Yuqi Liang,1,2,&ast; Guosong Wu,3,&ast; Tianyu Luo,1,2,&ast; Haimei Xie,2 Qian Zuo,2 Ping Huang,2 Huachao Li,2 Liushan Chen,2 Hai Lu,4,&ast; Qianjun Chen1,2,&ast; 1The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, People’s Republic of China; 2Department of Breast, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China; 3Nanfang Hospital Baiyun Branch, Guangzhou, Guangdong, 510000, People’s Republic of China; 4The First People’s Hospital of Shaoguan, Shaoguan, Guangdong, 512099, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qianjun Chen, Department of Breast, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Yuexiu District, Guangzhou, 510102, People’s Republic of China, Email cqj55@163.com Hai Lu, The First People’s Hospital of Shaoguan, No. 3, South Dongdi Road, Shaoguan, 512099, People’s Republic of China, Tel +86 15622187291, Email hysa1985@163.comPurpose: Although paclitaxel is widely used in cancer treatment, severe side effects and drug resistance limit its clinical use. 10-gingerol (10-G) is a natural compound isolated from ginger, which displays anti-inflammatory, antioxidant, and antiproliferative properties. However, the chemotherapy-sensitization effect of 10-G on triple-negative breast cancer (TNBC) has not been fully clarified. This study is aimed at investigating the effect of 10-G on the paclitaxel sensitivity in TNBC, and its underlying mechanism.Methods: The study was determined through in vitro and in vivo experiments. Cell viability and proliferation were detected by cell counting kit 8 (CCK-8) and colony formation. To detect cell apoptosis, flow cytometry and TUNEL were used. The expression of proteins was detected by Western blotting and immunohistochemistry. The molecular docking and gene knockout were corroborated by interactions between 10-G and adrenoceptor Beta 2 (ADRB2). The body weight of mice, histopathology and organs (kidney and spleen) coefficients were used to monitor the drug toxicities.Results: In vitro, 10-G increased the sensitivity of TNBC cells to paclitaxel, and could synergistically promote the apoptosis of TNBC cells induced by paclitaxel. In combination with molecular docking and lentivirus knockdown studies, ADRB2 was identified as a 10-G binding protein. 10-G inhibited ADRB2 by binding to the active site of ADRB2. Knockdown of ADRB2 reduces the proliferation activity of TNBC cells but also attenuates the sensitizing effects of 10-G to paclitaxel. Western blotting and immunohistochemistry showed that 10-G played an anti-proliferation and chemotherapy-sensitizing role by inhibiting the ADRB2/ERK signal. Toxicity evaluation showed that 10-G would not increase hepatorenal toxicity with paclitaxel.Conclusion: This data suggests that 10-G may be used as a new chemotherapeutic synergist in combination with paclitaxel to enhance anticancer activity. The potential value of ADRB2 as a target for improving chemotherapy sensitivity was also emphasized.Keywords: triple-negative breast cancer, combined therapies, 10-gingerol, paclitaxel, adrenoceptor Beta 2

Shuya Zhao,1 Yunyang Zhang,2 Yun Chen,3 Xianghui Xing,1 Yu Wang,1 Guofeng Wu4 1Department of Pediatric Dentistry, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China; 2Center of Modem Analysis, Nanjing University, Nanjing, People’s Republic of China; 3Department of Pediatric Dentistry, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, People’s Republic of China; 4Department of Prosthodontics, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of ChinaCorrespondence: Guofeng Wu; Xianghui Xing, Email wgffmmu@sina.com; dr.xing@qq.comPurpose: To evaluate the effects of dentin pretreatment with chitosan-loaded oleuropein nanoparticles (CONPs) on the durability of resin–dentin bonding interfaces.Methods: Eighty freshly extracted non-carious human third molars were randomly divided into four groups (n = 20 each): a de-ionized water (DW) group, a chitosan (CS) group, a chlorhexidine (CHX) group and a CONP group. The dentin in the DW, CS, CHX, and CONP groups were pretreated with de-ionized water, 1.0 mg/L CS solution, 2% chlorhexidine solution, and CONP suspension (prepared with 100 mg/L oleuropein), respectively, followed by the universal adhesive and resin composites. The bonded teeth of each group were randomly divided into two subgroups: an immediate subgroup and an aged subgroup. The bonded teeth of each group were then cut into the bonded beams. We measured their microtensile bond strength (μTBS), observed the characteristics of bonding interface by atomic force microscope, calculated the percentage of silver particles in a selected area for interfacial nanoleakage analysis, and evaluated the endogenous gelatinase activity within the bonding interface for in-situ zymogram analysis. Data were analyzed with two-way ANOVA and LSD multiple comparison test (P < 0.05).Results: Regardless of after 24 h or after thermocycling, CONP exhibited better μTBS (P < 0.05) than the other three groups except that there was not a statistical significance (P > 0.05) in the CONP and CHX groups after 24 h. Besides, the CONP group presented significantly higher modulus of elasticity in the hybrid layers (P < 0.05), lower expression of nanoleakage (P < 0.05), and better inhibitory effect of matrix metalloproteinases than the other three groups before and after thermocycling.Conclusion: Altogether, the CONPs had the potential to act as a dentin primer, which could effectively improve the dentin-resin binding durability.Keywords: atomic force microscopy, dentin, matrix metalloproteinases, microtensile bond strength, nanoleakage

Yiwen Dong,1– 3 Litao Yao,2– 4,&ast; Lei Cai,1 Mi Jin,1 Tymour Forouzanfar,2,3 Lianjun Wu,1 Jinsong Liu,1,&ast; Gang Wu2,3 1School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Science, Amsterdam, Amsterdam, the Netherlands; 3Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam (UvA) and Vrije Universiteit Amsterdam (VU), Amsterdam, the Netherlands; 4Department of Dentistry, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Litao Yao, Department of Dentistry, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China, Zhejiang, Email yaolt@srrsh.com Jinsong Liu, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China, Email jinsong0719@wmu.edu.cnIntroduction: An antibacterial and pro-osteogenic coaxially electrospun nanofiber guided bone regeneration (GBR) membrane was fabricated to satisfy the complicated and phased requirements of GBR process.Methods: In this study, we synthesize dual-functional coaxially electrospun nanofiber GBR membranes by encapsulating parathyroid hormone (PTH) in the core layer and magnesium oxide nanoparticles (MgONPs) in the shell layer (MgONPs-PCL/PTH-PCL). Herein, the physicochemical characterization of MgONPs-PCL/PTH-PCL, the release rates of MgONPs and PTH, and antibacterial efficiency of the new membrane were evaluated. Furthermore, the pro-osteogenicity of the membranes was assessed both in-vitro and in-vivo.Results: We successfully fabricated a coaxially electrospun nanofiber MgONPs-PCL/PTH-PCL membrane with the majority of nanofibers (> 65%) ranged from 0.40~0.60μm in diameter. MgONPs-PCL/PTH-PCL showed outstanding antibacterial potential against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) through the release of MgONPs. We also discovered that the incorporation of MgONPs significantly prolonged the release of PTH. Furthermore, both the in-vivo and in-vitro studies demonstrated that high dosage of PTH promoted pro-osteogenicity of the membrane to improve bone regeneration efficacy with the presence of MgONPs.Conclusion: The new composite membrane is a promising approach to enhance bone regeneration in periodontitis or peri-implantitis patients with large-volume bone defects.Keywords: antibacterial property, pro-osteogenicity, coaxially electrospun, barrier membrane, guided bone regeneration

Xuezhou Cai,1,2,* Wei Li,1,* Jian Yang,1,3,* Guangjie Wu,1 Jianxin Song,4 Xuepeng Gong,1 Dong Liu,1 Yan He1 1Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Pharmacy, Xianning Central Hospital, Hubei University of Science and Technology, Xianning, People’s Republic of China; 3Department of Pharmacy, General Hospital of Central Theater Command of Chinese People’s Liberation Army, Wuhan, People’s Republic of China; 4Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan He; Dong Liu, Email heyan_may@hotmail.com; ld2069@outlook.comBackground: There is a wide debate about the efficacy and safety of voriconazole in patients with impaired hepatic function at Child-Pugh C level.Objective: The purpose of this study was to investigate the safety and efficacy between the two groups treated with different dosages of voriconazole (400mg/day vs 200mg/day) in the treatment of invasive fungal infections (IFIs) in patients with hepatic dysfunction.Methods: A retrospective study enrolling patients with hepatic dysfunction receiving intravenous voriconazole for IFIs from January 1st, 2017, to December 30th, 2021 was conducted. Patients were enrolled in the 400mg per day dose group and 200mg per day dose group. In patients with the same degree of hepatic impairment, factors affecting prognosis were screened and differences in steady-state blood trough concentrations (Cmin) of voriconazole, positive G/GM tests and adverse effects (AEs) were compared between the two groups described above.Results: In total, 308 patients with IFIs were enrolled. For Child-Pugh C class, patients receiving the halved maintenance dose had a lower Cmin and AEs rate but higher recovered rate compared to those receiving maintenance dose, and significant predictors of recovery were dosage (OR, 5.131; 95% CI, 1.599– 16.464; p = 0.006) and diabetes (OR, 0.111; 95% CI, 0.020– 0.597; p = 0.010). For patients of Child-Pugh A & B class, chronic liver disease (OR, 0.334; 95% CI, 0.159– 0.704; p = 0.004) was a prognosis-related factor.Conclusion: Halving maintenance dose ensure the efficacy and safety of voriconazole in patients suffering from invasive fungal infections with serious hepatic dysfunction.Keywords: hepatic dysfunction, invasive fungal infections, voriconazole, through concentration, Child-Pugh

Anjun Song,1,&ast; Hui Yang,2,&ast; Guofeng Wu,1 Siying Ren,1 Likun Wang,1 Guannan Qin,1 Yuanhong Mao1 1Emergency Department, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Guiyang Public Health Treatment Center, Guiyang, Guizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Anjun Song, Email 351815967@qq.comObjective: The present study aimed to evaluate the clinical value of minimally invasive surgery for intracranial hematoma removal and high intracranial pressure (ICP) reduction using a novel three-needle brain puncture technique.Methods: A total of 202 cases with supratentorial hematoma were analyzed, 54 of whom received three-needle brain puncture (study group), and the remaining cases received single-needle (control groups 1 and 2) and two-needle brain puncture (control group 3). The amount of intracranial hematoma removed, changes in ICP, retention time of puncture needle, volume of residual blood, the National Institute of Health Stroke Scale (NIHSS) score, and postoperative survival rate were used as indexes to evaluate patient outcomes.Results: We found that three-needle brain puncture (study group) can remove more intracranial hematoma (P < 0.05) and achieve lower ICP (P < 0.05) than single- and two-needle brain puncture (control group). The needle retention time and volume of residual blood significantly decreased in the study group. Additionally, a statistically significant difference was observed in the NIHSS scores and survival rates between the study and control groups (P < 0.05).Conclusion: These data suggest that three-needle minimally invasive stereotactic puncture can effectively remove hematoma, reduce ICP, decrease the degree of brain damage, and improve prognosis.Keywords: cerebral hemorrhage, intracranial pressure monitoring, minimally invasive procedures, three-needle puncture, National Institute of Health Stroke Scale

Zhiquan Ding1 &ast;, Zhenzhong Zhong1 &ast;, Jun Wang1 &ast;, Run Zhang,2 Jinlian Shao,3 Yulong Li,1 Guiwei Wu,1 Huiru Tu,1 Wen Yuan,4 Haitao Sun,1,5 Qinghua Wang1,3 1Neurosurgery Center, Department of Neurotrauma and Neurocritical Care Medicine, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Neurosurgery Center, Department of Neuro-oncological Surgery, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 3Department of Emergency, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 4Laboratory Animal Center, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 5Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qinghua Wang; Haitao Sun, Neurosurgery Center, Department of Neurotrauma and Neurocritical Care Medicine, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China, Email wqh1123@126.com; 2009sht@smu.edu.cnBackground: Neuroinflammation plays an important role following intracerebral hemorrhage (ICH). NLRP3 inflammasome-mediated pyroptosis contributes to the mechanism of neuroinflammation. It has been reported that dendritic cell-associated C-type lectin-1 (Dectin-1) activation triggers inflammation in neurological diseases. However, the role of Dectin-1 on NLRP3 inflammasome-mediated pyroptosis after ICH remains unclear. Here, we aimed to explore the effect of Dectin-1 on NLRP3 inflammasome-mediated pyroptosis and neuroinflammation after ICH.Methods: Adult male C57BL/6 mice were used to establish the ICH model. Laminarin, an inhibitor of Dectin-1, was administered for intervention. Expression of Dectin-1 was evaluated by Western blot and immunofluorescence. Brain water content and neurobehavioral function were tested to assess brain edema and neurological performance. Western blot was conducted to evaluate the level of GSDMD-N. ELISA kits were used to measure the levels of IL-1β and IL-18. qRT–PCR and Western blot were performed to evaluate the expressions of NLRP3 inflammasome, IL-1β, and IL-18.Results: The expression of Dectin-1 increased following ICH, and Dectin-1 was expressed on microglia. In addition, inhibition of Dectin-1 by laminarin decreased brain edema and neurological impairment after ICH. Moreover, inhibition of Dectin-1 decreased the expression of pyroptosis-related protein, GSDMD-N, and inflammatory cytokines (IL-1β and IL-18). Mechanistically, Dectin-1 blockade inhibits NLRP3 inflammasome activation, thereby alleviating neuroinflammatory injury by attenuating NLRP3 inflammasome-mediated pyroptosis both in vivo and in vitro.Conclusion: Our study indicates that the inhibition of Dectin-1 alleviates neuroinflammation by attenuating NLRP3 inflammasome-mediated pyroptosis after ICH.Keywords: intracerebral hemorrhage, Dectin-1, NLRP3 inflammasome, pyroptosis, microglia

Tianyu Tan,1 Chao Zhou,1 Rongrong Lu,1 Cheng Chen,2 Chongyang Bai,1 Long Li,1 Guohui Wu1 1Chongqing Center for Disease Control and Prevention, Chongqing, 400042, People’s Republic of China; 2Chongqing Jiulongpo District Center for Disease Control and Prevention, Chongqing, 400039, People’s Republic of ChinaCorrespondence: Guohui Wu, Chongqing Center for Disease Control and Prevention, No. 8, Changjiang 2nd Road, Chongqing, 400042, People’s Republic of China, Tel +8602368801491, Email wgh68803652@163.comPurpose: This study aimed to assess the proportion of depression and its associated factors among men living with HIV/AIDS and aged 50 and over in Chongqing, China.Methods: This cross-sectional study included 774 men diagnosed as HIV/AIDS and aged 50 and over in four regions. Data were collected through face-to-face interviews with a structured questionnaire. Multivariate logistic regression analysis was performed to identify factors associated with depression. A two-tailed P-value less than 0.05 was considered as statistical significance.Results: A total of 293 participants (37.9%) reported depressive symptoms. Results from multivariate logistic regression suggested that individuals aged ≥ 70 (AOR = 1.99, 95% CI: 1.28– 3.08) and those living in rural areas (AOR = 2.79, 95% CI: 1.96– 3.97) were associated with higher odds of depression, while those being employed (AOR = 0.50, 95% CI: 0.32– 0.80) and with monthly income > 3000 CNY (AOR = 0.47, 95% CI: 0.30– 3.74) had lower odds of depression.Conclusion: Our findings indicate a high prevalence of depression among older men living with HIV/AIDS in Chongqing, China. Age, residence, employment, and income have been identified as potential risk factors of depressive symptoms. Mental-health intervention initiatives should be tailored to target adults with a higher risk of depression.Keywords: depression, China, older male, HIV/AIDS, influencing factors

Zhongshan Wang,1,&ast; Guangsheng Wu,2,&ast; Zhujun Yang,3 Xuejian Li,1 Zhihong Feng,1 Yimin Zhao1 1State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Department of Prosthodontics, School of Stomatology, Fourth Military Medical University, Xi’an, People’s Republic of China; 2Qingdao Special Servicemen Recuperation Center of PLA Navy, Qingdao, People’s Republic of China; 3Xi’an Central Hospital Affiliated to Xi’an Jiaotong University, Xi’an, Shaanxi, 710003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongshan Wang; Yimin Zhao, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Department of Prosthodontics, School of Stomatology, Fourth Military Medical University, Xi’an, 710032, People’s Republic of China, Tel/Fax +86-29-84776128, Email wzs_fmmu@163.com; zhaoymdentist@163.comPurpose: Forming a compact biological seal between the gingiva and the implant interface around the percutaneous parts of an implant is one of the key issues in preventing peri-implantitis.Methods: In this study, since microRNA-21 (miR-21) has been approved to promote fibroblast proliferation and collagen formation in skin fibrosis, we prepared miR-21-loaded chitosan (CS)/tripolyphosphate (TPP)/hyaluronic acid (HA) nanoparticles (CTH NPs) and cross-linked them to smooth Ti surfaces with 0.2% gel solution for reverse transfection, after which isolated human gingival fibroblasts were cultured on the miR-21-functionalized Ti substrates.Results: An optimal CS:TPP:HA ratio (1:0.15:0.1) and N/P ratio (20:1) were chosen to produce appropriate nanoparticles. Finally, the CTH/miR-21 nanoparticle-coated smooth Ti surfaces demonstrated increased fibroblast adhesion, proliferation and expression of extracellular matrix-related genes along with similar cytotoxicity and cell spreading on the miR-21-functionalized Ti surface and the unmodified smooth Ti surface.Conclusion: The chitosan-based nanoparticles might be an efficient nonviral miRNA vector to form a stable biological seal in percutaneous areas of Ti for clinical use.Keywords: microRNA, chitosan, hyaluronic acid, nanoparticle, percutaneous implant

Gujie Wu,1,&ast; Zhenyu Zhu,1,&ast; Zheng Yang,2,&ast; Min He,1 Kuan Ren,1 Yipeng Dong,1 Qun Xue3 1Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China; 2Department of Respiratory medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China; 3Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qun Xue, Email ntfyxuequn@163.comBackground: Lung squamous cell carcinoma (LUSC) is a malignant tumour of the lung epithelium. A hypoxic environment can promote tumour cell proliferation and invasion. Therefore, this study aims to explore hypoxia-related genes and construct reliable models to predict the prognosis, cellular processes, immune microenvironment and target compounds of lung squamous carcinoma.Methods: The transcriptome data and matched clinical information of LUSC were retrieved from The Cancer Genome Atlas (TCGA) database. The GSVA algorithm calculated each LUSC patient’s hypoxia score, and all LUSC patients were divided into the high hypoxia score group and low hypoxia score group. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis were performed to screen out differentially expressed hypoxia-related genes (DE-HRGs) in LUSC microenvironment, and the underlying regulatory mechanism of DE-HRGs in LUSC was explored through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Hereafter, we established a prognosis-related genetic signature for DE-HRGs using univariate and multivariate Cox regression analyses. The relationship between gene signature and immune cells was further evaluated. Finally, the Comparative Toxicogenomics Database (CTD) was utilized to predict the targeted drugs for the prognostic genes.Results: We obtained 376 DE-HRGs. Functional enrichment analysis indicated that the DE-HRGs were involved in the cell cycle-related regulatory processes. Next, we developed and validated 3 HRGs-based prognostic signature for LUSC, including HELLS, GPRIN1, and FAM83A. Risk score is an independent prognostic factor for LUSC. Functional enrichment analysis and immune landscape analysis suggested that the risk scoring system might be involved in altering the immune microenvironment of LUSC patients to influence patient outcomes. Ultimately, a total of 92 potential compounds were predicted for the three prognostic genes.Conclusion: In summary, we developed and validated a hypoxia-related model for LUSC, reflecting the cellular processes and immune microenvironment characteristics and predicting the prognostic outcomes and targeted compounds.Keywords: lung squamous cell carcinoma, hypoxia, prognosis, immune, targeted compounds

Gujie Wu,1,&ast; Min He,1,&ast; Kuan Ren,1,&ast; Huiyun Ma,1 Qun Xue2 1Medical School of Nantong University, Nantong, People’s Republic of China; 2Cardiothoracic Surgery Department, Affiliated Hospital of Nantong University, Nantong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qun Xue, Email ntfyxuequn@163.comBackground: Inducible co-stimulator (ICOS) is a cell-enhanced co-stimulatory receptor that has shown great potential in the regulation of innate and adaptive immunity. However, the role of ICOS in lung adenocarcinoma (LUAD) remains unclear.Methods: We used data from the Cancer Genome Atlas(TCGA) database to identify the expression and prognostic role of ICOS in LUAD. The results were validated using Gene Expression Omnibus(GEO) and Kaplan-Meier plotter databases. A model with predictive performance for overall survival of LUAD patients was constructed using fitted ICOS expression and other clinical parameters. We explored the biological function of ICOS. Subsequently, we further analysed and validated the effect of ICOS expression on tumour immune microenvironment (TIME) and survival. Finally, the CellMiner database was used to determine the relationship between ICOS expression and drug sensitivity.Results: ICOS expression is significantly associated with poor prognosis in multiple cancers, especially LUAD, and is a good predictor of overall survival in LUAD patients. The biological function is to promote autoimmunity and inhibit cell proliferation. ICOS-related survival prediction model developed to more accurately predict 1-, 3- and 5-year survival probabilities for LUAD patients. In addition, we can use the expression of ICOS to effectively assess patient malignancy, prognosis, TIME status and clinical combination of drugs.Conclusion: Our results suggest that ICOS is correlated with prognosis and immune infiltrating levels in LUAD. Higher ICOS expression predicts better TIME. This study provides a novel strategy for the development of immunotherapeutic and prognostic markers in LUAD.Keywords: ICOS, lung adenocarcinoma, prognosis, immune infiltration, drug sensitivity

Yaqiang Li,1,2 Mei Zhang,1 Chunhui Dong,3 Min Xue,1 Jing Li,1 Guixiang Wu2 1Department of Neurology, First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, Huainan, 232001, Anhui, People’s Republic of China; 2Department of Neurology, People’s Hospital of Lixin County, Lixin, 236700, Anhui, People’s Republic of China; 3School of Medicine, Anhui University of Science and Technology, Huainan, 232001, Anhui, People’s Republic of ChinaCorrespondence: Mei Zhang; Min Xue, Department of Neurology, First Affiliated Hospital of Anhui University of Science and Technology, First People’s Hospital of Huainan, 203 Huaibin Road, Huainan, 232007, Anhui Province, People’s Republic of China, Tel +86 13955466855 ; +86 13866336522, Email hnzhangmei2008@163.com; xuemingxx@163.comPurpose: Red blood cell distribution width (RDW) is closely related to inflammatory-related disease markers. The present study aimed to investigate the association between the red blood cell distribution width (RDW) and post-stroke depression (PSD).Patients and Methods: A total of 414 patients with acute ischemic stroke (AIS) admitted to our hospital from June 2018 to July 2021 were consecutively enrolled and received 3 months’ follow-up. According to the 17-item Hamilton Depression Scale (HAMD) assessment, they were divided into PSD group and non-PSD group. Diagnosis of PSD was made in accordance with DSM-IV. RDW was recorded within 24 hours of admission.Results: Among the included 414 patients, 95 (22.95%) patients were diagnosed as having PSD at 3 months after stroke. The results showed significantly higher level of RDW in patients with depression (13.69 (IQR13.24– 13.88) vs. 13.56 (IQR 12.67– 13.77), P< 0.001) at admission than patients without depression. After adjustment for potential confounding factors, the odds ratio of PSD was 5.707 (95% CI, 2.717– 11.989) for the highest tertile of RDW compared with the lowest tertile. Moreover, based on the receiver operating characteristic (ROC) curve, the optimal cutoff of RDW levels as an indicator for the prediction of PSD was projected as 13.01, which yielded a sensitivity of 83% and a specificity of 41.0%, with an area under the curve (AUC) of 0.643 (95% CI, 0.585– 0.701; P = 0.012).Conclusion: Higher RDW levels at admission were found to be correlated with PSD 3 months after stroke.Keywords: inflammation, red blood cell distribution width, depression, stroke

Yuqiong Lin,1 Ying Xu,1 Xin Zheng,1 Jingwen Zhang,1 Junfeng Liu,1 Guotu Wu2 1Department of Basic Medical Science, Fujian Health College, Fuzhou, 350101, Fujian Province, People’s Republic of China; 2Department of Basic Medical Science, Fujian Medical University, Fuzhou, 350101, Fujian Province, People’s Republic of ChinaCorrespondence: Yuqiong LinDepartment of Basic Medical Science, Fujian Health College, No. 366 Jingxi Town, Fuzhou, 350101, Fujian Province, People’s Republic of ChinaEmail yuqiong90@sina.comBackground: Absolute or relative lack of insulin secretion caused by pancreatic β-cell dysfunction can lead to diabetes. Astragaloside IV (AS-IV), the main components of the traditional Chinese medicine Astragalus, has anti-oxidant, anti-inflammatory and anti-apoptotic properties, and exerts anti-diabetic pharmacological effects.Purpose: To explore whether AS-IV can protect the apoptosis and dysfunction of pancreatic β-cells induced by streptozotocin (STZ) and its underlying molecular mechanism.Methods: STZ-induced pancreatic β-cell line INS-1 was treated with different concentrations of AS-IV, then cell viability, apoptosis, oxidative stress and insulin secretion was assessed by CCK-8, TUNEL staining, Western blot, commercial kits and qRT-PCR, respectively. The expression of proteins involved in Sirtuin 1 (SIRT1)/p53 and Akt/glycogen synthase kinase-3 β (GSK3β)/nuclear factor E2-related factor 2 (Nrf2) signaling was measured by Western blot assay. Besides, Akt inhibitor MK-2206 and SIRT1 inhibitor EX-527 were used to co-treat STZ-induced INS-1 cells in the presence of AS-IV, and the above experiments were repeated.Results: AS-IV increased the cell viability of INS-1 cells induced by STZ. AS-IV also reduced the increase in apoptosis rate and reversed STZ-induced down-regulation of Bcl-2 and up-regulation of Bax and Cleaved caspase 3. In addition, AS-IV significantly reduced STZ-induced malondialdehyde upregulation and reduced superoxide dismutase and glutathione peroxidase levels. Furthermore, the use of AS-IV was found to increase the insulin secretion capacity of INS-1 cells with impaired function, along with the increase of the mRNA levels of insulin 1 and insulin 2. Mechanism studies further showed that MK-2206 and EX-527 reversed the protective effect of AS-IV against STZ-induced injury on INS-1 cells.Conclusion: AS-IV exerted cytoprotective effect on STZ-induced INS-1 cells through regulating SIRT1/p53 and Akt/GSK3β/Nrf2 signaling pathways. These findings are expected to provide new supplements to the molecular mechanism of AS-IV in the treatment of diabetes.Keywords: astragaloside IV, pancreatic β-cell, apoptosis, dysfunction, SIRT1/p53, Akt/GSK3β/Nrf2

The fluorides from spent carbon cathodes could be effectively solidified in a molten copper smelting slag (FeO-Fe3O4-SiO2- CaO-Al2O3) in forms of CaF2 and Ca4Si2F2O7. The results of thermodynamic analysis, chemical analysis, and XRD and EPMA analyses showed that the F solidification efficiency increased with the CaO amount and decreased with the addition of Al2O3 and SiO2. In addition, it was noteworthy that the F solidification efficiency decreased with an excessive CaO amount, which could be ascribed to the consumption of SiO2 through forming CaSiO3 and Ca3Si2O7. It restricted the solidification of the fluoride into Ca4Si2F2O7. Under the conditions of melting temperature of 1300°C, residence time of 60 min, and N2 flow rate of 40 ml/min, the optimum CaO and NaF amounts were found to be 20 wt.% and 6 wt.%, respectively, in which the F solidification efficiency in the copper smelting slag of FeO-Fe3O4-SiO2-CaO-Al2O3 obtained 98.35%.

Tao Wang,1,&ast; Lei Dong,2,&ast; Juanjuan Sun,3,&ast; Jialiang Shao,1 Jian Zhang,1 Siteng Chen,1 Chaofu Wang,2 Gangfeng Wu,4 Xiang Wang1 1Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Pathology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Urology, Shaoxing People’s Hospital, Shaoxing, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gangfeng WuDepartment of Urology, Shaoxing People’s Hospital, No. 568 Zhongxing North Road, Shaoxing, Zhejiang, 312000, People’s Republic of ChinaEmail gaffwu@sina.comXiang WangDepartment of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of ChinaEmail xiang.wang1@shgh.cnBackground: The Gleason grading system is a major tool used for prediction of prostate cancer (PCa) behavior. Because of heterogeneity and sampling errors, prognosis is variable even among patients with the same Gleason score (GS). Therefore, more accurate biomarkers that complement the Gleason system are needed to improve the clinical management of PCa.Methods: Formalin-fixed, paraffin embedded tissue samples were obtained from radical prostatectomy (RP) (patient set 1, n=53) and needle biopsy (patient set 2, n=107; patient set 3, n=119). Cancer tissues from pure regions of each Gleason pattern (GP) were separately collected using laser-captured microdissection, followed by Real-time-PCR to determine the relative expression of miRNAs, including miR-1-5p, miR-21-5p, miR-30d-5p, miR-100-5p, miR-145-5p, miR-224-5p, and miR-708-5p. miRNA’s association with Gleason upgrading (GU) was evaluated using receiver operator characteristics (ROC) curve and multivariate logistic regression analysis. The integrated miRNA targets prediction and enrichment analyses were performed to determine the potential functions of miRNA.Results: It was found that miR-145-5p in GP3 from radical prostatectomy (RP) were overexpressed in patients with GS6 PCa compared with GS7 patients, which was further confirmed in a larger biopsy cohort. ROC curve analysis revealed that miR-145-5p in biopsy was significantly associated with GU upon RP. In multivariate analyses, miR-145-5p was an independent predictor of GU.Conclusion: Our study indicated that differential expression of miRNAs existed in GP3 from pure GS6 and GS7 PCa, highlighting a path toward the clinical use of miRNAs in predicting GU and assisting in treatment modality selection.Keywords: prostate cancer, microRNA, biopsy, active surveillance, Gleason upgrading

Kai Wang,1,2,&ast; Wenjun Xu,3,&ast; Bingbing Zha,1 Jindong Shi,2 Guowei Wu,3 Heyuan Ding1,3 1Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Nephrology, Zhejiang Kaihua County Hospital of Chinese Medicine, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Heyuan DingDepartment of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, 801 Heqing Road, Minhang District, Shanghai, 200240, People’s Republic of ChinaEmail heyuan.ding@fudan.edu.cnGuowei WuDepartment of Nephrology, Zhejiang Kaihua County Hospital of Chinese Medicine, 10 Zhongshan Road, Kaihua County, Zhejiang, 324399, People’s Republic of ChinaEmail kh22005@sohu.comPurpose: Diabetic kidney disease (DKD) is an inflammatory disease. This study aimed to investigate the association of fibrinogen to albumin ratio (FAR) with DKD.Patients and Methods: A total of 1022 type 2 diabetes mellitus (T2DM) patients with DKD and 1203 T2DM patients without DKD were enrolled in this study. Laboratory values including blood cell count, hemoglobin A1c, biochemical parameters, and fibrinogen and albumin creatinine ratio were recorded. Patients were classified according to tertile of admission FAR. Clinical parameters were compared between groups. Logistic regression, linear regression, ROC analysis and spline regression were carried out.Results: FAR in the DKD group was significantly higher than that in the non-DKD group. FAR had the highest odds ratio as an independent risk factor for the development of DKD and the highest area under ROC curve for predicting DKD compared with albumin (ALB) or fibrinogen (FIB) alone. Simple linear regression analyses revealed a significant and linear correlation of FAR with neutrophil and neutrophil-to-lymphocyte ratio. FAR was an independent risk factor for development of DKD. Spline regression showed that there was a significant linear association between DKD incidence and continuous FAR value when it exceeded 67.3mg/g.Conclusion: FAR is a stronger independent predictor of DKD than FIB and ALB. FAR is an independent risk factor for DKD development when it exceeded 67.3mg/g. FAR might be one of novel diagnostic biomarkers to predict and prevent DKD progression. However, a prospective study to validate the prognostic model is still needed.Keywords: type 2 diabetes mellitus, diabetic kidney disease, inflammation, fibrinogen to albumin ratio

Xu Chen,1,2,&ast; Jing Yang,3,&ast; Hailan Shen,4 Xuemei Zhang,1 Hong Wang,1 Guangying Wu,1 Yuhong Qi,1 Ling Wang,1 Wenchun Xu1 1Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, School of Laboratory Medicine, Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Clinical Laboratory, First People’s Hospital of Liangshan Yi Autonomous Prefecture, Xichang, Sichuan, People’s Republic of China; 3Department of Clinical Laboratory, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 4Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenchun XuKey Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, School of Laboratory Medicine, Chongqing Medical University, Chongqing, People’s Republic of ChinaTel +86-2368485239Email xuwen@cqmu.edu.cnIntroduction: LncRNAs play important roles in multiple diseases including asthma, while there are a few reports on the role of lncRNA H19 about asthma. This study aimed to investigate the roles and mechanisms of lncRNA H19 in asthma.Methods: We detected lncRNA H19 and Muc5ac mRNA by establishing a murine asthma model and an in vitro inflammation model. Regulatory roles of lncRNA H19 in asthma were explored by lncRNA H19 overexpression or knockdown in vitro. To study its mechanisms, we detect p-NF-κB and p-Akt expression, and treated 16-HBE cells with inhibitors of PI3K. To study regulatory effects of miR-675-3p on Muc5ac, miR-675-3p mimics and inhibitors were respectively transfected into 16-HBE cells.Results: Firstly, we established a murine asthma model and an in vitro inflammation model. We found that lncRNA H19 expression was decreased, while Muc5ac mRNA was increased in lung tissues of murine asthma model and in the in vitro inflammation model. lncRNA H19 overexpression increased Muc5ac mRNA expression and lncRNA H19 knockdown decreased Muc5ac mRNA expression in 16-HBE cells. Moreover, lncRNA H19 overexpression further increased Muc5ac expression in TNFα-induced in vitro inflammation model. lncRNA H19 knockdown decreased p-Akt and p-NF-κB expression. Inhibitors of PI3K abolished Muc5ac induced by lncRNA H19 overexpression. Although miR-675-3p was increased by lncRNA H19 overexpression, it had no regulatory effects on Muc5ac expression.Discussion: These results demonstrated that lncRNA H19 positively regulates Muc5ac expression through PI3K/Akt /NF-κB pathway in the in vitro inflammation model. Therefore, this study indicated that decreased lncRNA H19 in asthma might play a protective role relieving mucus overproduction, and lncRNA H19 might be a potential target for asthma treatment.Keywords: asthma, lncRNA H19, Muc5ac, NF-κB, Akt

Meirong Xu,1 Ganlin Wu2,3 1Department of Geriatrics, The Second Affiliated Hospital of Hubei University of Science and Technology, Xianning, 437100, Hubei Province, People’s Republic of China; 2Department of Medicine, School of Clinical Medicine Sciences, Hubei University of Science and Technology, Xianning, 437100, Hubei Province, People’s Republic of China; 3National Demonstration Center for Experimental General Medicine Education (Hubei University of Science and Technology), Xianning, 437100, Hubei Province, People’s Republic of ChinaCorrespondence: Ganlin WuDepartment of Medicine, School of Clinical Medicine Sciences, Hubei University of Science and Technology, No. 88 Xianning Road, Xianning, 437100, Hubei Province, People’s Republic of ChinaTel +86-0715-8102568Email wu_ganlin65@21cn.comIntroduction: This study was to test whether the serum levels of IL-33 and sST2 are correlated with the development of depression after acute ischemic stroke.Methods: Patients diagnosed with acute ischemic stroke were selected. This study took the 24-item Hamilton Depression Rating Scale (HAMD) (score ≥ 20) as the diagnostic criteria for depression. On the 21st day after admission, patients who met the depression diagnostic criteria were included in the depression group, and patients who failed to meet the diagnostic criteria were included in the non-depression group. The serum levels of IL-33, sST2 and hsCRP were measured by enzyme-linked immunosorbent assay (ELISA).Results: On 1st day after stroke, compared with the non-depression group, there was no significant difference in the serum IL-33, sST2 and hsCRP levels in the depression group; on 21st day after stroke, compared with the non-depression group, the serum IL-33 and hsCRP levels were significantly increased, while the sST2 level was significantly decreased in the depression group. Correlation analysis showed that IL-33 was positively correlated with the depression quantitative score and hsCRP, while sST2 was negatively correlated with the depression quantitative score and hsCRP. Regression analysis showed that IL-33 and sST2 were independent risk factors for the depression after acute ischemic stroke.Discussion: The abnormal alterations of serum IL-33 and sST2 levels in the stroke patients may serve as one of the risk factors for the occurrence and exacerbation of the depression, and its mechanism may be related to the promotion of inflammatory factor production in vivo.Keywords: IL-33, sST2, post-stroke depression, PSD, clinical significance, risk factor

Xilin Liu,* Da Huo,* Guangzhi Wu Department of Hand Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guangzhi Wu Tel +86-13944181019Email wuguangzhi@jlu.edu.cnBackground/Purpose: Anterolateral thigh perforator (ALTP) flap and deep inferior epigastric perforator (DIEP) flap have been advantageous over traditional myocutaneous flaps as they preserve the integrity of donor site muscles and minimize the damage and complication to donor site structures. Here, we reported the efficacy of free ALTP and DIEP in the repair of large skin area and soft tissue defects on both lower limbs after trauma.Case Report: A 19-year-old female traffic accident victim presented with multiple open bilateral fractures to the lower extremities with joint dislocation, massive skin and soft tissue defects, and multiple soft tissue contusion. Wounds on both lower extremities were covered with VSD (Vacuum Sealing Drainage). The tibiofibular and ankle joints on both lower limbs were fixed using external fixators. DIEP and ALTP flap were performed at different times.Results: After transfer, the vascular pedicle was anastomosed to the anterior tibial artery, posterior tibial artery, and the accompanying vein. After the operation, the donor site was directly closed and sutured. All flaps survived with a good appearance, leaving only a linear scar at the donor site.Conclusion: This case shows that free ALTP and DIEP flaps are ideal for repairing large skin area and soft tissue defects in bilateral lower limbs after trauma.Keywords: anterolateral thigh perforator flap, deep inferior epigastric perforator flap, soft tissue repair, skin repair

Bo Zhao,1,* Renjing Hu,2,* Lei Gong,1 Xiaoyun Wang,1 Yingwei Zhu,1 Gaojue Wu1 1Department of Gastroenterology, The Affiliated Wuxi Second People’s Hospital of Nanjing Medical University, Wuxi, People’s Republic of China; 2Department of Clinical Laboratory, The Affiliated Wuxi Second People’s Hospital of Nanjing Medical University, Wuxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoyun WangDepartment of Gastroenterology, The Affiliated Wuxi Second People’s Hospital of Nanjing Medical University, Wuxi, People’s Republic of ChinaTel +86 15061857125Fax +86 510 685662052Email xiaoyunwang68@aliyun.comRationale: Klebsiella pneumoniae (K. pneumoniae, KP) are divided into two types: classic K. pneumoniae (cKP) and hypervirulent K. pneumoniae (hvKP). hvKP causes liver abscess and metastatic infection. Here, we report one case with pyogenic liver abscess (PLA) and endogenous endophthalmitis (EE) due to a relatively rarely reported serotype of K. pneumoniae in China.Patient Concerns: An 80-year old man presented with nausea, vomiting, and epigastric discomfort for 2 weeks.Diagnoses: PLA was identified by CT scan and abdominal ultrasound. Urgent ophthalmologic consultation was performed. B-scan ocular ultrasound was done and he was diagnosed as EE.Interventions: Antibiotic treatment, intravitreal injection of eyes and eye drops were given. Percutaneous needle aspiration, evisceration, and drainage of the right eye were performed.Outcomes: Cultures of the blood, the aspirated pus from the liver abscess, and the contents of the eyeball all yielded K. pneumoniae with a positive string test. The capsular serotype was K64. According to the existence of multiple virulence genes and the severe invasive clinical manifestation, this strain is regarded as a hvKp strain. Multilocus sequence typing (MLST) revealed the sequence type (ST) of this strain was K64-ST1764. Antimicrobial resistance genes, blaNDM-1 and blaKPC-2, were not detected in the genome. The patient lost his eyesight but his symptoms subsided. During 15 months follow-up, the result was satisfactory.Lessons: Here, we report one case with PLA due to a relatively rarely reported serotype of K. pneumoniae in China. This K64 K. pneumoniae strain is confirmed as hvKp by multiple methods. It is noteworthy that the sequence type is K64-ST1764 instead of the commonest ST11. Moreover, this strain is not considered a K. pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) or a carbapenem-resistant K. pneumoniae (CRKP) as it is usually. Further follow-up and research are required to investigate this strain.Keywords: case report, hypervirulent Klebsiella pneumoniae, pyogenic liver abscess, antibiotic resistance, ultrasonography guided puncture aspiration

Mechanical soft reduction (MSR) is an effective method for elimination of the centerline segregation and porosity of the continuous casting steel slab, and the reduction amount is a key parameter that determines whether the MSR could be applied successfully. In the present work, a 2D heat transfer model was developed for predicting the non-uniform solidification of the wide-thick slab. The measured shell thickness by nail shooting experiment and the measured slab surface temperature by infrared camera were applied to validate the 2D heat transfer model. A new calculation method of theoretical reduction amount that could consider the influence of non-uniform solidification of the wide-thick slab was then derived. Based on the predicted temperature field by the 2D heat transfer model and the newly-proposed calculation method, the required theoretical reduction amount and reduction gradient/rate for the wide-thick slab were calculated and discussed. The difference between the newly-proposed method and the previous method, the influence of the casting speed and slab thickness on the required theoretical reduction amount and reduction gradient/rate were also investigated.

Hailu Wu,1,2 Ming Wei,2 Nan Li,2 Qin Lu,2 Sachin Mulmi Shrestha,1 Jiacheng Tan,2 Zhenyu Zhang,3 Guoqiu Wu,4,5 Ruihua Shi2 1Medical School of Southeast University, Nanjing 210009, People’s Republic of China; 2Department of Gastroenterology, Zhongda Hospital Affiliated to Southeast University, Nanjing 210009, People’s Republic of China; 3Division of Gastroenterology, Department of Medicine, Nanjing Medical University Nanjing First Hospital, Nanjing 210009, People’s Republic of China; 4Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, People’s Republic of China; 5Jiangsu Provincial Key Laboratory of Critical Care Medicine, Nanjing 210009, People’s Republic of ChinaCorrespondence: Ruihua ShiDepartment of Gastroenterology, Zhongda Hospital Affiliated to Southeast University, Nanjing 210009, People’s Republic of ChinaTel +86 25 83262833Fax +86 25 83262830Email ruihuashi@126.comGuoqiu WuCenter of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, People’s Republic of ChinaTel +86-25 83272150Email nationball@163.comAim: Although Clopidogrel is safe in healthy volunteers, it can induce recurrence of gastric ulcers in high-risk patients. Here, we investigated the protective effect of the natural product, stable gastric pentadecapeptide 157 (BPC 157) on Clopidogrel-induced gastric injury.Methods: We used acetic acid to induce gastric ulcer in Sprague Dawley rats. Clopidogrel alone or in combination with BPC 157 or L-NAME (nitric oxide system blockade) were administered after healing of acetic acid-induced ulcer. One percent methylcellulose solution was used as control. Ulcer recurrence rate and the ulcer index were compared between these groups. Gastric mucosal apoptosis rate, microscopic inflammation activity and angiogenesis markers vascular endothelial growth factor A (VEGF-A) and CD34 were examined by TUNEL, histological evaluations (HE) and immunohistochemistry (IHC). Pathways involved, expressions of endoplasmic reticulum (ER) stress apoptosis marker CHOP, angiogenic markers VEGF-A and its receptor VEGFR1, and endothelial NO synthase (eNOS) were all analyzed by Western blot.Results: This study indicated that Clopidogrel significantly induced the gastric ulcers recurrence, severe inflammation and ER stress related apoptosis of the gastric mucosa, suppressed the synthesis of angiogenic markers and eNOS. Furthermore, Clopidrogel intervention resulted in the activation of protein kinase B (AKT) and p38 mitogen-activated protein kinase (p38/MAPK). BPC 157 attenuated the gastric mucosal damage caused by Clopidogrel and reversed these molecular effects. However, NO blockade L-NAME weakened the protective effect and thus the molecular effects of BPC 157 on gastric mucosa.Conclusion: In conclusion, these results suggest that BPC 157 inhibited Clopidogrel-induced gastric mucosa injury partially by inhibition of gastric mucosa cell ER stress-mediated apoptosis and inflammation, and promoting gastric mucosa angiogenesis via VEGF-A/VEGFR1 mediated-AKT/p38/MAPK signaling pathways.Keywords: clopidogrel, BPC 157, angiogenesis, AKT, p38/MAPK