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Qiufeng Wei,1,&ast; Heng Rong,1,&ast; Guangying Zhang,1 Yubo Xie,2 Weixin Dai1 1Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, 530021, People’s Republic of China; 2Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weixin Dai, Department of Anesthesiology, The First affiliated Hospital of Guangxi Medical University, No. 6 of Shuangyong Road, Nanning, 530021, Guangxi Province, People’s Republic of China, Tel +86 13507713016, Email yfy003902@sr.gxmu.edu.cn Yubo Xie, Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, No. 6 of Shuangyong Road, Nanning, 530021, Guangxi Province, People’s Republic of China, Tel +86 0771-5356250, Email yuboxie_gxmu@126.comObjective: Research has revealed that patients with diabetes and peripheral neuropathy exhibit significantly elevated nerve stimulation thresholds. However, the minimum stimulation thresholds of peripheral nerves in patients with diabetic foot, along with the recovery of nerve function, remain undetermined. The aim of this study is to investigate the minimum stimulation thresholds of the femoral and sciatic nerves, as well as the duration of nerve block, in patients diagnosed with diabetic foot.Methods: From July 2020 to March 2022, a prospective study was conducted involving patients aged 50– 80 scheduled for distal lower limb surgery. The study included 83 patients with diabetic foot and 48 individuals without diabetes. Prior to surgery, an ultrasound-guided approach combined with nerve stimulation was employed to administer a popliteal sciatic nerve block (20 mL of ropivacaine 5 mg/mL) and a femoral nerve block (20 mL of ropivacaine 5 mg/mL). During the ultrasound-guided femoral and popliteal sciatic nerve blocks, the electric current required to elicit motor activity in both the femoral and popliteal sciatic nerves was assessed.Results: The study revealed that patients with diabetic foot exhibited significantly higher stimulation thresholds for femoral and sciatic nerve blocks, as well as a substantially longer duration of femoral and sciatic sensory and motor blocks (P < 0.01). Additionally, nerve injury was observed in 4 patients (4.8%) within the diabetes mellitus (DM) group.Conclusion: Patients with diabetic foot exhibit higher minimum stimulus thresholds for the femoral and sciatic nerves and experience delayed recovery from ropivacaine block.Keywords: diabetic foot, nerve damage, nerve blocks, minimal stimulation threshold, ultrasound

Jiaxuan He,1,&ast; Peiye Xu,1,&ast; Rongbing Chen,2 Mengyan Chen,3 Beier Wang,4 Yilun Xie,4 Qinsi Yang,5 Da Sun,1 Mingxia Ji3 1Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, 325035, People’s Republic of China; 2Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, SAR 999077, People’s Republic of China; 3Department of Critical Care Medicine, Yiwu Central Hospital, the Affiliated Yiwu Hospital of Wenzhou Medical University, Yiwu, 322000, People’s Republic of China; 4Department of Hepatobiliary-Pancreatic Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 5Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingxia Ji; Da Sun, Email jmx529652@wmu.edu.cn; sunday@wzu.edu.cnAbstract: Sepsis, a severe condition instigated by infections, continues to be a primary global cause of death, typified by systemic inflammation and advancing immune dysfunction. Comprehending the complex pathological processes that underlie sepsis is integral to the creation of efficacious treatments. Despite the inability of animal models to entirely reproduce the clinical intricacies related to sepsis, they are invaluable instruments for the exploration and development of therapeutic approaches. Within this context, the zebrafish model is particularly noteworthy due to its genetic tractability, transparency, and appropriateness for high-throughput screening of genetic mutants and therapeutic compounds. This scholarly review emphasizes the crucial role that the zebrafish disease model plays in enhancing our comprehension of sepsis, by exploring its applications in deciphering immune and inflammatory responses, evaluating the consequences of genetic alterations, and examining novel therapeutic agents. The Insights derived from zebrafish research not only augment our understanding of the underlying mechanisms of sepsis, but also possess considerable potential for the transference of these discoveries into clinical therapies, thus potentially transforming the approach to sepsis management. The objective of this scholarly article is to underscore the importance of zebrafish in the realm of biomedical research pertaining to sepsis, and to delineate forthcoming opportunities for utilizing this model in clinical applications. Keywords: Sepsis, Zebrafish models, Inflammation, Immunology, Drug development

Quanfeng Liao,1 Yu Feng,2 Jin Deng,1 Weili Zhang,1 Siying Wu,1 Ya Liu,1 Yi Xie,1 Mei Kang1 1Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Mei Kang, Email kangmei@sina.comObjective: Ceftazidime-avibactam (CZA) is a novel β-lactam/β-lactamase inhibitor with activity against carbapenem-resistant Klebsiella pneumoniae (CRKP) that produce Klebsiella pneumoniae carbapenemase (KPC). In this study, we report the first cases of CZA resistance to develop during treatment of CRKP infections and identify the resistance mechanism.Methods: APB/EDTA and NG-Test CARBA5 were used to detect the production of carbapenemase, whole-genome sequencing (WGS) and conjugation experiment were used to identify potential resistance mechanisms of CZA-susceptible (HX1032) and -resistant (HX1192) K. pneumoniae isolates.Results: HX1192 K. pneumoniae was not recognized by APB/EDTA and NG-Test CARBA5 phenotypic assays, WGS revealed it carrying a novel KPC variant, KPC-179, molecular analysis highlighted a G394A mutation, and an ATC insertion at 543 in the blaKPC-2 gene, resulting in an A133T substitution and insertion of the amino acid S at Ambler position 183 in the protein sequence. Remarkably, this mutation restored susceptibility of imipenem (MIC = 0.25 mg/L).Conclusion: Our study highlights the importance of monitoring susceptibility during CZA treatment and accurately detecting KPC variants.Keywords: CZA resistance, carbapenem-resistant, Klebsiella pneumoniae, KPC variant, phenotypic test

Yuling Liang,1,&ast; Yuqing Xie,1,&ast; Zhibo Dang,2,&ast; Mengge Li,3,&ast; Lihua Yu,1 Xinhui Wang,4 Peng Wang,5 Zhiyun Yang1 1Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Ethics Committee Office, Henan Province Hospital of TCM, Henan, People’s Republic of China; 3Department of Hepatobiliary Spleen and Stomach, Henan Province Hospital of TCM, Henan, People’s Republic of China; 4Beijing Children’s Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Department of Pathology, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Wang, Department of Pathology, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China, Tel +86-10-84322530, Email dtpengwang@163.com; dtwangpeng@mail.ccmu.edu.cn Zhiyun Yang, Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China, Tel +86-10-84,322,148, Email yangzhiyun2016@163.comPurpose: Yiqi Liangxue Jiedu prescription (YLJP), a Chinese medicine that is commonly used to prevent liver cancer and is authorized by a national patent (patent No. ZL202110889980.5) has a therapeutic effect on precancerous lesions; however, the underlying mechanism remains unclear. This study is aimed at determining the clinical therapeutic efficacy of YLJP in patients with precancerous liver lesions and to explore and validate its possible effector mechanism.Patients and Methods: The 1-year incidence of hepatocellular carcinoma (HCC) was retrospectively analyzed in 241 patients with cirrhosis complicated by abnormal alpha-fetoprotein precancer. Network pharmacological analysis, molecular docking, and molecular dynamics simulation were used to explore the key targets and compounds of YLJP in treating HCC. Immunohistochemical methods were used to detect the expression of key proteins in tumor and cirrhotic tissues. Finally, the mechanism underlying the effects of YLJP was verified in rats with precancerous lesions.Results: The 1-year incidence of HCC was lower in the YLJP group than in the Western medicine group. The Wnt pathway protein, CTNNB1, is a key target of YLJP in preventing and treating HCC, and the canonical Wnt pathway is the key signaling pathway and is overexpressed in human liver tumors. In vivo experiments showed that YLJP significantly inhibited the canonical Wnt pathway and reduced the abnormal differentiation of hepatic oval cells. The binding of CTNNB1 to oleanolic acid, stigmasterol, and beta-sitosterol was found to be stable, indicating the action of these compounds in treating HCC.Conclusion: YLJP reduces the 1-year incidence of HCC, with its mechanism likely due to oleanolic acid, beta-sitosterol, and stigmasterol inhibition of the CTNNB1 activation of the β-catenin protein, which in turn regulates the Wnt signaling pathway and prevents the abnormal differentiation of hepatic oval cells into cancer cells, thus delaying the occurrence and progression of the disease.Keywords: network pharmacological analysis, molecular docking, molecular dynamics simulation, hepatocellular carcinoma, Wnt / β-catenin

Most patients are at advanced stages when they are diagnosed with hepatocellular carcinoma, leading to poor prognosis and a low 5-year survival rate. Serological markers, ultrasound, computed tomography, magnetic resonance imaging, positron emission tomography, and liver biopsy are the common clinical diagnostic techniques for liver cancer. Effective interventions in the early stage will be beneficial to improve the prognosis of liver cancer patients and reduce the global burden. Therefore, it is urgent to develop new diagnostic methods to improve the diagnosis and management of liver cancer. Nanotechnology has become a new frontier subject in medical detection along with the application of nanomaterials in the manufacture of drug carriers, diagnostic tools, and therapeutic devices. Many studies have shown that nanoparticles (NPs) can be applied to the clinical diagnosis of liver cancer in combination with existing technologies, providing a new method for the early diagnosis of liver cancer. In this review, we elaborate on the theoretical basis and characteristics of NPs in the diagnosis of liver cancer, and the research progress and prospects of NPs in the diagnosis of liver cancer are summarized.

Yehong Xie, Shunning Jiang, Qiaoling Liang, Xuezhu Hu, Dahai He, Xiaoheng Wu Chengdu University of Traditional Chinese Medicine Third Clinical Medical College/Affiliated Third Hospital, Pidu District Traditional Chinese Medicine Hospital, Chengdu, Sichuan, 611730, People’s Republic of ChinaCorrespondence: Xiaoheng Wu, Pidu District Traditional Chinese Medicine Hospital, Chengdu, Sichuan, 611730, People’s Republic of China, Email xiaohengwu1997@126.comAbstract: Moraxella catarrhalis (MC) is an aerobic Gram-negative cocci known to cause respiratory tract infections in humans as an opportunistic pathogen, with infections in other body parts being rare. This case involves an elderly female patient with a medical history of hypertension, type 2 diabetes, coronary heart disease, and osteoporosis. Following coronary angiography and lumbar spine surgery prompted by lower back and left lower limb pain, the patient developed persistent pus discharge from the lumbar spine wound post-surgery, which did not respond to conventional anti-infection therapy, leading to her transfer to our hospital. Upon examination, Direct Radiography (DR) diagram revealed gas accumulation and bone curling in the 4– 5 intervertebral space, muscle layer, and fascia layer of the lumbar vertebrae. Subsequent culture of the wound pus confirmed the presence of MC, resulting in a diagnosis of postoperative lumbar spine infection. Treatment involved antibiotics administration, lesion clearance, spinal exploration, and autologous iliac bone transplantation for fusion, alongside the management of glucose levels and hypertension, anticoagulation therapy, as well as the use of Duhuo Jisheng Decoction to promote blood circulation and eliminate blood stasis. Following this comprehensive treatment approach, the patient achieved a full recovery and was discharged. To the best of our knowledge, this is the first reported case of Moraxella catarrhalis infection following lumbar spinal fixation and fusion in Sichuan Province, China. The exact cause of infection in this case remains unclear. However, this case emphasizes the importance of considering the colonization site and infection mechanism of MC beyond the respiratory tract, underscoring the need for vigilance in clinical practice beyond typical infection sites.Keywords: Moraxella catarrhalis, lumbar spinal, fixation and fusion, case report

You Zhou,1– 3 Yingli Xie,2 Jingjing Dong,2 Kunlun He,1,3,&ast; Hebin Che1,3,&ast; 1School of Medicine, Nankai University, Tianjin, 300071, People’s Republic of China; 2The First Affiliated Hospital and Clinical Medicine College, Henan University of Science and Technology, Luoyang, Henan, 471003, People’s Republic of China; 3Medical Innovation Research Department, People’s Liberation Army General Hospital, Beijing, 100853, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hebin Che, Medical Innovation Research Department, People’s Liberation Army General Hospital, No. 28 Fuxing Road, Beijing, 100853, People’s Republic of China, Email chehebin@301hospital.com.cn Kunlun He, School of Medicine, Nankai University, No. 94 Weijin Road, Tianjin, 300071, People’s Republic of China, Email kunlunhe_301@163.comBackground: Patients with chronic heart failure (CHF) and type 2 diabetes mellitus (DM) are prone to insulin resistance and malnutrition, both of which are significant prognostic factors for CHF. However, the combined effect of the triglyceride–glucose index (TyG index) and prognostic nutritional index (PNI) on the mortality risk in patients with CHF and type 2 DM has not yet been studied.Methods: We enrolled 3,315 patients with CHF and type 2 DM. We used a multivariate Cox regression model to assess hazard ratios (HRs) with 95% confidence intervals (CIs) for mortality risk based on TyG index and PNI levels. Furthermore, we constructed a novel index, the insulin resistance–nutritional index (IRNI), defined as TyG index/Ln (PNI), and evaluated its prognostic significance.Results: During follow-up, 1,214 deaths occurred. Participants with a high TyG index and non-high PNI had a significantly higher mortality risk compared to those with a non-high TyG index and high PNI, with an adjusted HR of 1.91 (95% CI, 1.57– 2.32). The multivariate Cox regression analysis revealed HRs for all-cause and cardiovascular deaths of 1.93 (95% CI, 1.66– 2.26; P < 0.001) and 2.50 (95% CI, 2.05– 3.06; P < 0.001), respectively, when comparing the highest and lowest IRNI tertiles. IRNI’s predictive power was stronger in groups with higher adapted Diabetes Complications Severity Index scores (P for interaction < 0.05). Additionally, adding IRNI to the baseline risk model significantly improved predictive performance, showing a greater effect compared to the TyG index or PNI.Conclusion: IRNI, a novel and composite index reflecting insulin resistance and nutritional status, emerges as a potentially valuable prognostic marker for patients with CHF and type 2 DM.Keywords: combined effect, prognostic nutritional index, triglyceride–glucose index, insulin resistance–nutritional index, chronic heart failure and type 2 diabetes

Rong-Rong Huang,1 Yu-Sheng Xie,2 Gui-Ru Chen,3 Zhao-Qing Liu2 1Department of Burns and Plastic Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2School of Nursing, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 3Department of Infectious Diseases, The People’s Hospital of Aba Tibetan and Qiang Autonomous Prefecture, Aba, Sichuan, People’s Republic of ChinaCorrespondence: Gui-Ru Chen, Department of Infectious Diseases, The People’s Hospital of Aba Tibetan and Qiang Autonomous Prefecture, No. 176 Majiang Road, Maerkang, Aba Tibetan and Qiang Autonomous Prefecture, Sichuan, 624000, People’s Republic of China, Email 2017283030185@whu.edu.cnAim: The Barriers to Error Disclosure Assessment (BEDA) tool is used to measure barriers to the disclosure of medical errors by healthcare professionals. This study aimed to evaluate the psychometric properties of the Chinese version of the BEDA (C-BEDA).Background: The culture of disclosure and transparency in response to medical errors has been recommended in recent years. However, there are no relevant assessment tools for measuring barriers to disclosing medical errors in China.Methods: The C-BEDA tool underwent translation, back translation, cross-cultural adaptation in a pilot study. It was tested with 1254 healthcare professionals in Guizhou and Sichuan Provinces, China. The content validity index (CVI) was used to evaluate the content validity of the C-BEDA, and exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to evaluate its structural validity. The Cronbach’s α coefficient and test-retest reliability were evaluated to determine its reliability.Results: Three factors were extracted by EFA that explained 65.892% of the total variance of the C-BEDA tool. CFA showed a good fit for a three-factor structure with acceptable values: goodness-of-fit index=0.939; adjusted goodness-of-fit index=0.911; incremental fit index=0.967; comparative fit index=0.967; partial least squares path modeling for confirmatory factor analysis=0.735; and root mean square error of approximation=0.058. The item-level content validity index ranged from 0.86 to 1.00, and the average scale-level content validity index was 0.98. The Cronbach’s α coefficient (0.909) and test-retest reliability (0.86) were acceptable.Conclusion: The C-BEDA toolis a valid and reliable tool for assessing the extent of barriers to error disclosure among Chinese healthcare professionals.Keywords: patient safety, medical error, disclosure, risk management

With advancements in radiology, endoscopic techniques, surgical treatments, cell biology and molecular biology, the understanding of temporomandibular disorders(TMD)has increased. The temporomandibular joint (TMJ) is a complex structure comprising both soft and hard tissues. Within the TMJ, the temporomandibular disc is a soft tissue structure that connects the mandible to the skull, providing cushioning and stability during joint movement. Different imaging techniques have their own advantages and limitations in the diagnosis and treatment of TMD. Therefore, using image registration technology to assess the condition and position of the articular disc provides new research perspectives for evaluating TMD, which may contribute to the diagnosis and treatment. This article reviews the latest advancements in TMJ imaging, explores the applications of various image registration techniques, particularly in the context of TMD diagnosis and treatment, and discusses future prospects. Combining the research results of some scholars at home and abroad with the author’s clinical experience, the article aims to provide valuable insights for clinicians.

The stigma associated with functional neurological disorder (FND) is greater than that associated with other neurological conditions, seriously affecting the quality of life of patients and increasing the burden on caregivers. This article reviews the concept, the current situation and harms, the influence factors and intervention strategies of FND stigma. The aim is to further develop our country as a reference for the study of stigma in FND.

Objective To investigate the morphological and proteomic differences in exosomes (EXOs) during the storage of leukocyte-free apheresis platelets (LFA-Plt), evaluate the quality of platelets in storage and predict the function of EXOs at different storage periods. Methods EXOs were isolated by ultracentrifugation, then the morphological observation was performed by electron microscope. Particle size analysis and WB protein index detection were performed. 4D Label-free quantitative proteomics technology was used to perform quantitative and bioinformatics analysis on identified proteins. Protein differential analysis on the LFA- Plt EXO between group day 3 and day 5 was performed, and GO function and KEGG pathway enrichment analysis on differential proteins was conducted. Results Cup shaped, CD9/TSG101 enriched and Calnexin (-) EXO was successfully obtained. The particle size (nm) of LFA-Plt EXO for day 3 and day 5 were (82.2±19.6) and (83.4±19.4) respectively, and the protein concentration(μ g/uL) were (0.55±0.13) and (0.51±0.08) respectively, with no statistically significant difference between two groups (P>0.05). 1 504 proteins were identified in all samples. GO functional enrichment analysis showed that the LFA-Plt EXO proteins were mainly concentrated in the cell membrane, extracellular domain and proteasome core complex, and were related to the binding ability of proteins, ATP, calcium ions and GTP, and mainly participated in processes such as redox, protein hydrolysis and signal transduction. KEGG functional annotation showed that the EXO proteins mainly participated in material transportation and catabolism, genetic information processing, and were closely related to human tumors and viral bacterial infections, affecting the metabolism of human immune system. Compared with day 3, day 5 EXO showed significant up-regulation in 16 proteins. The GO enrichment analysis showed that 16 upregulated proteins were mainly associated with adenosine homocysteine activity and 6-phosphofructose kinase activity, and were mainly involved in the metabolism of organic nitrogen compound. KEGG enrichment pathway analysis showed that the most important function of upregulated proteins was participating in signaling pathway for oocyte maturation mediated by progesterone. Conclusion Under the preparation and storage conditions of LFA-Plt in our center, platelet quality can be relatively stable. The functions of EXO proteins varies with different storage periods, which may affect the effectiveness of platelet transfusion.

Objective To analyze the nucleic acid testing(NAT) results of voluntary blood donors in Hainan and evaluate the residual risk in the window period of NAT for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Methods A retrospective analysis on the NAT results of voluntary blood donors at our center from January 2012 to December 2022 was conducted. The new infection rate-window period residual risk model was used to assess the residual risk of HBV, HCV and HIV among blood donors. Results From January 2012 to December 2022, among the blood donated by voluntary blood donors in Hainan, 45.02% (522 684/1 161 042) were collected from first-time donors, 54.98% (638 358/1 161 042) were from repeat donors (including regular donors), and 30.48% (354 227/1 162 042) were from regular donors. The total reactive rate of NAT was 0.19% (2 151/1 161 042). After NAT, the residual risk in the window period of HBV, HCV and HIV was 62.54 per million, 0.431 per million and 0.791 per million, respectively. Conclusion The implementation of NAT among voluntary blood donors in Hainan significantly reduces the residual risk of HCV, and the residual risk of HBV, HCV and HIV transmission in the window period is at a relatively low level.

【Objective】 Southern Xinjiang has limited freshwater but relatively abundant saline groundwater. To optimize the use of these water resources, we investigate the effect of alternate brackish and freshwater drip irrigation with film mulching on soil water and salt movement, as well as seed yield of cotton. 【Method】 The experiment was conducted at the Xinjiang Alar Modern Agricultural Comprehensive Experimental Station. It compared nine combinations of brackish and freshwater drip irrigation. In each treatment, we measured the spatiotemporal changes in soil water and salt, as well as growth, and seed yield of the cotton. 【Result】 During the growth period of the cotton, soil water and salt increased with increased use of brackish water. When the amount of brackish water used for irrigation was the same, continuous use of freshwater irrigation in the early growth stage of the cotton was effective to reduce salt content in the root zone. Increasing the use of brackish water in irrigation inhibited crop growth. Moderate use of brackish water in the flowering and boll development stages can promote reproductive growth, however, excessive use would significantly reduce the weight of single bolls. Appropriately alternating brackish and freshwater irrigation not only ensures vegetative growth in the early stages but also promotes reproductive growth during flowering and boll development stage of the cotton. 【Conclusion】 In Southern Xinjiang, alternating brackish and freshwater in drip irrigation with film mulching should keep the brackish water ratio below a specific threshold. Its usage should be minimized during the seedling, budding, and early flowering stages, but can be increased during the flowering and boll development stages. In this experiment, the optimal irrigation sequence was freshwater-freshwater-brackish water.

BackgroundBipolar disorder is a severe mental disorder characterized by cycling between mania/hypomania and depression， yet its underlying pathophysiological mechanism remains unclear. Several prior studies have suggested a potential role for voltage-gated calcium channel subunit genes in the etiology of bipolar disorder， particularly in their influence on brain structure.ObjectiveTo investigate the differences in grey matter volume （GMV） for individuals with bipolar disorder compared to healthy controls， and to explore the potential influence of calcium channel voltage-dependent T-type α1 G subunit （CACNA1G） rs757415 polymorphism on GMV in bipolar disorder and clarify the specific brain regions associated with this genetic variation， thus offering a new opportunity to gain insight into the pathophysiological mechanism of bipolar disorder.MethodsA cohort of 289 patients who met the Diagnostic and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） criteria for bipolar disorder were selected for participation. These patients were either admitted to hospital or examined in outpatient clinic for bipolar disorder at the Mental Health Center of West China Hospital， Sichuan University between September 2013 and December 2022. Another 322 healthy individuals were concurrently recruited as a control group from Sichuan University and surrounding communities. All participants underwent brain imaging using a 3.0 T magnetic resonance scanner to acquire data on GMV. Additionally， the presence of the CACNA1G rs757415 polymorphism was validated using the imLDRTM technique. Spearman correlation analysis was utilized to investigate potential relationship between abnormal brain regions identified through GMV data and clinical characteristics of the patients. Then the genotype-by-diagnosis interaction effect for CACNA1G rs757415 on GMV was observed using the full factor method.ResultsThe study successfully enrolled 173 patients with bipolar disorder and 207 healthy controls who completed all the necessary procedures. Analyses revealed decreased GMV for patients with bipolar disorder compared to healthy controls in the left cerebellar declive extending to cerebellar anterior/posterior lobe， fusiform gyrus， parahippocampal gyrus and inferior occipital gyrus （t=5.664， P

Mengli Tang,1,&ast; Xingbing Lu,1,&ast; Yuxiao Li,2 Yuzuo Chen,1 Yi Xie1 1Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2West China School of Medicine, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Xie, Department of Laboratory Medicine, West China Hospital, Sichuan University, Guoxue Lane37, Chengdu, Sichuan, People’s Republic of China, Tel +86-028-85422618, Email xieyi@scu.edu.cnAbstract: Listeria monocytogenes is a prevalent gram-positive intracellular zoonotic pathogen that is frequently associated with foodborne illnesses and opportunistic infections. This bacterium is responsible for causing various clinical manifestations, including bacteremia, meningitis, and encephalitis, and is primarily transmitted through contaminated food consumption. This study presents two cases of severe endocarditis in patients with heart valve disease caused by L. monocytogenes. Infection was confirmed by blood culture and pathogen culture of the valve pus. Early detection, clinical suspicion, and appropriate treatment are crucial for improving the prognosis of patients with listeriosis. The combination of ampicillin and aminoglycosides remains the most effective treatment for listeriosis.Keywords: infective endocarditis, Listeria monocytogenes, heart valve disease

Zhu Y, Cheng M, Yang Z, et al. Drug Des Devel Ther. 2014;8:2449–2462. The authors have advised that figure parts 2E and 4B on pages 2454 and 2456, respectively, are incorrect. An error at the time of figure assembly led to the inadvertent duplication of images in both figures. The correct Figure 2 and 4 are shown below. Figure 2 Continued. Figure 2 Transduction of NK4 cDNA into human MSCs using a lentiviral vector and characterization.Abbreviations: GFP, green fluorescent protein; conc, concentration; HGF, hepatocyte growth factor; ANOVA, analysis of variance; rhHGF, recombinant human hepatocyte growth factor; MOI, multiplicity of infection; Mr, molecular weight; MSCs, mesenchymal stem cells; cDNA, complementary DNA.Notes: The recombinant pGC-FU-GFP-NK4-plasmids, the construction plasmids Helper1.0, and the envelope plasmids Helper2.0 (GeneChem Co., Ltd., Shanghai, People’s Republic of China) were first cotransfected into 293T cells. MSCs were then transduced with Lenti-NK4 (MSCs-NK4) or Lenti-GFP (MSCs-GFP) at varying multiplicity of infection (MOI). (A) Expression of GFP in MSCs observed at day three after Lenti-NK4 infection at MOI of 10, 20, 50, or 100 under fluorescence microscopy, (B) transduction efficiency of Lenti-NK4 in MSCs determined by flow cytometry with an GFP marker which was 87.8% of the enriched GFP-expressing MSC population upon sorting with an MOI of 50, (C) effect of transduction with Lenti-NK4 at different MOIs from 1 to 100 in MSCs on the production of NK4 in the culture medium, (D) effect of time on the production of NK4 in the culture medium after MSCs were transduced with Lenti-NK4 (MOI =50), Lenti-GFP (MOI =50), or not transduced, (E) MSCs-NK4 with increased GFP expression observed at different time points (MOI =50, from Day 1 to Day 3), and (F) Western blot analysis of NK4-GFP fusion protein with a molecular weight of 84 kDa. Recombinant human HGF (Mr =83 kDa) was used as a positive control. *P

ObjectiveTo understand the epidemiological characteristics of recovered COVID-19 cases with re-positive nucleic acid in Pudong New Area of Shanghai, and to provide a reference for the prevention and control of COVID-19.MethodsA three-month health follow-up and nucleic acid testing were conducted on 339 COVID-19 cases cured and discharged between May 20 and June 20, 2022, in Pudong New Area, Shanghai, to analyze their epidemiological characteristics.ResultsAmong the 339 follow-up cases, 75 cases experienced re-positive nucleic acid results, with a recurrence rate of 22.12%. Factors such as gender, age group, occupation, presence of heart disease, hypertension, and full vaccination status had no effect on the re-positive results. Being diagnosed as a confirmed case during the first presence of infection, having diabetes, and a hospitalization period of ≤7 days were related factors for recurrence. The median interval between discharge and re-positive nucleic acid results was 26 days. The close contacts of the re-positive cases did not contract COVID-19 after the isolation and observation period.ConclusionThere is a possibility of re-positive nucleic acid results after COVID-19 recovery and discharge. Cases initially diagnosed as confirmed cases and those with a hospitalization period of no more than 7 days have a high rate of re-positivity. No secondary transmission is observed from the re-positive cases.

Objective China is the largest producer of rare earth element (REE) and hosts the largest amount of REE resources. Various types of REE deposits have been reported in China, with alkaline-carbonatite related light REE deposits and ion-adsorption heavy REE deposits being the most important ones. Other REE deposit types include REE placers and deposits with REE by-products. Currently, the development of rare earth resources in China is primarily focused carbonatite-alkaline related light REE deposits and ion-adsorption type heavy REE deposits. REE in placer deposits and other REE by-products have not been effectively utilized. Methods Based on existing exploration studies and whole-rock REE geochemistry data analysis, this study provides a brief review of the types and resource potential of deposits with REE by-products in China. Results China's by-products REE resource types include marine sedimentary phosphate, coal, bauxite, and magmatic iron-phosphate deposits. These deposits, particularly marine sedimentary phosphate deposits and bauxite, contain enormous potential REE resources. REEs in bauxite are primarily light REE, with some containing high amount of scandium (Sc). In sedimentary phosphate deposits, the proportion of heavy REEs (including yttrium) is high, particularly in the S−P−Al−Sr rich ores that occur as the layers overlying the phosphorite in the Shifang-type phosphate deposits of Sichuan Province. These S−P−Al−Sr rich ores have significantly higher REE content than phosphorite, with medium and heavy REE accounting for over 50%, along with various critical metals, making these ores highly valuable in terms of both resource and economic significance. Furthermore, REE resources in magmatic (iron) phosphate deposits, coal, oil shale, and gold deposits deserve attention. Conclusions Owing to the lack of detailed exploration data, the full extent of China's by-products REE resources remains unclear. The comprehensive utilization of resources, as well as the technology for REE recovery and extraction, requires improvement. Significance Strengthening the evaluation and comprehensive utilization of China's associated REE resources, particularly by fully utilizing the REE resources associated with phosphate and bauxite deposits, can effectively alleviate the pressure on China's HREE supply. This represents an important measure for implementing China's fundamental national policies on resource conservation and environmental protection.

Implementation strategies are targeted interventions aimed at promoting the adoption, implementation, and sustainment of research findings or evidence-based practices in routine healthcare. If implementation strategies can precisely match implementation barriers and facilitators, the likelihood of successful implementation will increase. The CFIR-ERIC matching tool, which can match corresponding ERIC implementation strategies based on CFIR barriers, is a convenient and direct tool for developing implementation strategies. This paper provides a detailed overview of the origins and development of the CFIR-ERIC matching tool, outlines its contents and usage, and illustrates how to apply the tool to develop implementation strategies by using a brief smoking cessation intervention project as an example. The paper also discusses the advantages and limitations of using this tool for developing implementation strategies, with the aim of providing methodological reference for other researchers.

Xi Cao,1 Yong-Li Xie,2,3 Jian-Ying Yi,1 Zhi-Li Liu,4 Meng Han,1 Ji-hui Duan,1 Qiang Gao,1 Hong Mu,1 Chun-lei Zhou1 1Department of Clinical Laboratory, Tianjin First Central Hospital, Tianjin, People’s Republic of China; 2Department of Clinical Laboratory, Tianjin Stomatological Hospital, School of Medicine, Nankai University, Tianjin, People’s Republic of China; 3Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, People’s Republic of China; 4Department of Clinical Laboratory, the Third Central Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Hong Mu; Chun-lei Zhou, Department of Clinical Laboratory, Tianjin First Central Hospital, Tianjin, People’s Republic of China, Email mutjyzxyy@163.com; tj_zcl@hotmail.comPurpose: The emergence of the SARS-CoV-2 Omicron variant has posed a significant global public health challenge. Elucidating the laboratory profiles of individuals infected with this variant is crucial for assessing organ damage. This study aimed to investigate the variations in liver function tests and their correlation with demographic characteristics and inflammatory markers in patients with early Omicron variant infections.Patients and Methods: A retrospective cohort study was conducted on 1133 mild or asymptomatic COVID-19 cases at Tianjin First Central Hospital. Data on age, gender, body mass index (BMI), and serum markers were collected and analyzed. Statistical analyses were performed using SPSS software, version 24.0.Results: Abnormal liver function parameters, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and total bilirubin (TBIL), were observed in 314 (27.71%) patients. “Hepatocellular type” was identified in 56 (4.94%) patients, “cholestatic type” in 185 (16.33%) patients, and “mixed type” in 73 (6.44%) patients. In the mixed group, we observed a pronounced elevation in the levels of ALT, AST, and GGT. Moreover, the hepatocellular group exhibited a statistically significant increase in AST and ALT concentrations relative to both the normal and cholestatic groups. Notably, the cholestatic group demonstrated a substantial increment in ALP levels. Males had a significantly higher prevalence of “abnormal liver enzyme markers” compared to females. Patients with “abnormal liver enzyme markers” exhibited significantly decreased immunoglobulin G (IgG) levels and elevated levels of inflammatory markers, including procalcitonin (PCT), interleukin-6 (IL6), as well as C-reactive protein (CRP) compared to normal group. Logistic regression analysis revealed that male gender and PCT levels were significantly associated with the risk of abnormal liver enzyme markers. Patients in hepatocellular group were likely accompanied with high CRP levels, whereas those in the cholestatic type were associated with high IL6 levels.Conclusion: Early Omicron infection might cause liver stress response. Elevated liver enzyme marker levels were correlated with age, gender, inflammatory factors, and IgG.Keywords: Omicron variant, “abnormal liver enzyme markers”, male, inflammatory markers

Abstract Low-frequency repetitive transcranial magnetic stimulation (rTMS) has emerged as an effective intervention for alleviating symptoms of psychiatric disorders, particularly schizophrenia characterized by persistent auditory verbal hallucinations (AVH). However, the underlying mechanism of its action remain elusive. This study employed a randomized controlled design to investigate the impact of low-frequency rTMS on the neural connectivity at the stimulate site, specifically left temporoparietal junction (TPJ), in schizophrenia patients with suffering from AVH. Using Dynamic Causal Modeling (DCM), this study assessed changes in directed connectivity patterns and their correlations with clinical symptomatology. The results demonstrated significant improvements in AVH. Notably, significant changes in connectivity were observed, including both abnormal functional connectivity and effective connectivity among multiple brain regions. Particularly, the inhibition effects from the left precentral gyrus and left medial superior frontal gyrus to the left TPJ were closely associated with improvements in AVH. These findings underscore the potential of rTMS to effectively modulate neural pathways implicated in hallucinations in schizophrenia, thereby providing a neurobiological foundation for its therapeutic effects.

Yang Xie, Xiangyang Sun, Fubo Xie, Wencheng Jian, Qingliang Wang, Xiaochen Ma, Caixia Li, Kai Zhang Department of Radiology, Qilu Hospital of Shandong University, Shandong, People’s Republic of ChinaCorrespondence: Kai Zhang, Department of Radiology, Qilu Hospital of Shandong University, Shandong, People’s Republic of China, Tel +8618560081593, Email fifa6107@126.comPurpose: To examine the relationship between lactate dehydrogenase (LDH) levels and soluble programmed cell death-ligand 1 (sPD-L1) levels in hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE).Methods: A total of 83 hCC patients participated in this study. Patients were categorized into subgroups based on their alpha-fetoprotein (AFP) levels, presence or absence of extrahepatic metastasis, vascular invasion, Barcelona Clinic Liver Cancer (BCLC) stage, tumor response, tumor size, and number LDH and sPD-L1 levels were compared before and after TACE (3, 7, and 30 days post-TACE).Results: LDH and sPD-L1 levels were significantly higher at 3 and 7 days post-TACE than at baseline. Positive correlations were observed between changes in LDH levels and sPD-L1 levels at 3 and 7 days post-TACE. LDH levels were higher in patients with elevated AFP compared to those in the normal AFP group at 3 and 7 days post-TACE, in the stable disease (SD) group compared to complete response (CR) and partial response (PR) groups at 7 days post-TACE, and in those with tumor > 5 cm compared with those with tumor ≤ 5 cm at 3 and 7 days after TACE (all P < 0.05). sPD-L1 levels were higher in patients with vascular invasion than those without vascular invasion at 3 and 7 days post-TACE, in the SD group compared to CR and PR groups at 3 and 7 days post-TACE, and in those with tumor > 5 cm compared to those with tumor < 5 cm at 3 and 7 days after TACE (all P < 0.05).Conclusion: A positive correlation was found between LDH expression and sPD-L1 levels, suggesting LDH as a potential biomarker for assessing immune status in HCC patients following TACE.Keywords: hepatocellular carcinoma, immunotherapy, lactate dehydrogenase, soluble programmed cell death ligand-1, transarterial chemoembolization

Fangqian Du,1,&ast; Yuwei Xie,1,&ast; Shengze Wu,1 Mengling Ji,2 Bingzi Dong,3 Chengzhan Zhu1 1Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Department of Surgery, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan; 3Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chengzhan Zhu, Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Tel +86 0532-82919552, Fax +86 0532-82911885, Email zhuchengz@qduhospital.cn Bingzi Dong, Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Tel/Fax +86-82911383, Email dongbingzi@hotmail.comAbstract: Hepatobiliary and pancreatic diseases are becoming increasingly common worldwide and associated cancers are prone to recurrence and metastasis. For a more accurate treatment, new therapeutic strategies are urgently needed. The claudins (CLDN) family comprises a class of membrane proteins that are the main components of tight junctions, and are essential for forming intercellular barriers and maintaining cellular polarity. In mammals, the claudin family contains at least 27 transmembrane proteins and plays a major role in mediating cell adhesion and paracellular permeability. Multiple claudin proteins are altered in various cancers, including gastric cancer (GC), esophageal cancer (EC), hepatocellular carcinoma (HCC), pancreatic cancer (PC), colorectal cancer (CRC) and breast cancer (BC). An increasing number of studies have shown that claudins are closely associated with the occurrence and development of hepatobiliary and pancreatic diseases. Interestingly, claudin proteins exhibit different effects on cancer progression in different tumor tissues, including tumor suppression and promotion. In addition, various claudin proteins are currently being studied as potential diagnostic and therapeutic targets, including claudin-3, claudin-4, claudin-18.2, etc. In this article, the functional phenotype, molecular mechanism, and targeted application of the claudin family in hepatobiliary and pancreatic diseases are reviewed, with an emphasis on claudin-1, claudin-4, claudin-7 and claudin-18.2, and the current situation and future prospects are proposed.Keywords: claudins, hepatocellular carcinoma, cholangiocarcinoma, pancreatic cancer, targeted therapy

Zhen Wang,1,&ast; Hui Xu,1,2,&ast; Zheng Wang,1,&ast; Yu Wang,3,&ast; Jieyao Diao,1 Juntao Chen,1 Yuchen Xie,4 Lijuan Zhang,5 Miaoxiu Li,6 Yanqin Bian,7 Yunfeng Zhou1 1College of Acupuncture and Massage, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2Tuina Department, The Third Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 3College of Computer Science, Xidian University, Xian, People’s Republic of China; 4Tuina Department, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou, People’s Republic of China; 5Rehabilitation Department, Jiaozuo Coal Industry (Group) Co. Ltd. Central Hospital, Jiaozuo, People’s Republic of China; 6College of Acupuncture and Massage, Shanghai University of Chinese Medicine, Shanghai, People’s Republic of China; 7Orthopaedic Research Laboratory, University of California, Davis, CA, USA&ast;These authors contributed equally to this workCorrespondence: Hui Xu; Yunfeng Zhou, Email 15036065036@163.com; zyf5680198@126.comBackground: Knee osteoarthritis (KOA) is on the rise due to lifestyle changes, obesity, and aging, yet effective treatments are lacking. Traditional Chinese manual therapy (Tuina) is promising for KOA. However, its mechanism remains unclear.Objective: This study aims to determine the effects of Tuina on a rat KOA model, focusing on the role of chondrocyte apoptosis and autophagy mechanisms.Methods: KOA was induced in rats by intra-articular injection of L-cysteine-activated papain into the right knee. Thirty-six male Sprague Dawley (SD) rats were randomly divided into blank, model control, Tuina, and positive drug groups. Paw withdrawal threshold tests, knee joint swelling, and passive range of motion assessed knee behavior. Cartilage tissue cytology, cytokine contents, and the mRNA and protein expression of PI3K/AKT/mTOR signaling pathway components were analyzed using HE and TUNEL staining, ELISA, RT-qPCR, and Western blotting, respectively. In addition, we used machine learning methods to conduct a secondary analysis of the dataset from the in vivo experiments in rats to verify the findings.Results: Tuina significantly relieved pain and joint swelling, and improved range of motion. Staining showed reduced articular cartilage destruction and apoptosis. Tuina reduced the serum levels of IL-1β, IL-17, MMP-3, and MMP-13. Tuina downregulated Bax, ULK1, Beclin-1, LC3-II/I and upregulated PI3K, AKT, mTOR, and BCL-2 in cartilage tissue. The machine learning results indicated an 83.33% accuracy for the prediction model, remaining stable through both uni- and multivariate analyses. Tuina yielded the best comprehensive efficacy on KOA as well as better rat behavior and PI3K/AKT/mTOR signaling pathway improvement effect than positive drugs, while its cytokine-reducing ability was comparable to that of positive drugs.Conclusion: Tuina can alleviate cartilage tissue injury in KOA, relieve inflammation, and reduce chondrocyte apoptosis and autophagy, the underlying mechanisms of which may be associated with activation of the PI3K/AKT/mTOR signaling pathway.Keywords: knee osteoarthritis, apoptosis, autophagy, tuina, PI3K/AKT/mTOR signaling pathway, in vivo experiment, machine learning

During the operation of jack-up offshore platforms, the complex and variable seabed geological conditions involved can lead to serious accidents, such as pile leg punctures and platform tilt. The aim of this study is to introduce an early warning method for punctures that ensures the operational safety of these platforms. To accomplish this, a real-time monitoring and controlling system is designed using a programmable logic controller that shares data from sensors measuring displacement, tilt, and pressure. In addition, an experimental device is constructed to simulate a jack-up offshore platform in order to assess the safety response of the control system. The working state of the platform under different working conditions (puncture of one independent pile, same side or diagonal piles, and three-pile linkage) is evaluated by analysing the structural motion response, including platform tilt and foundation pressure. The findings reveal that the system developed in this study accurately detects the tilt condition of the offshore platform, and can ensure the operational safety of jack-up offshore platforms.

Sweetpotato is an important crop whose roots are consumed by people worldwide. Meloidogyne enterolobii stands out as a highly deleterious variant among the species of root-knot nematode that causes significant damage in sweetpotato. In the present study, the activity of four nematicides against M. enterolobii was assessed both in vitro and in growth cabinet experiments. After 48 hours of exposure, fluopyram and cyclobutrifluram had a greater negative effect on the motility of M. enterolobii second-stage juveniles (J2s) compared to fluensulfone and hymexazol, with respective median effective concentration (EC50) values of 0.204, 0.423, 22.335 and 216.622 mg L−1. When M. enterolobii eggs were incubated for 72 hours at the highest concentration of each nematicides, the inhibitory hatching effect of cyclobutrifluram (2.5 mg L−1), fluopyram (1.25 mg L−1) and fluensulfone (80 mg L−1) surpassed 85%, whereas hymexazol (640 mg L−1) was only 67%. Similar results were observed in growth cabinet experiments as well. The disease index (DI) and gall index (GI) were significantly decreased by all four nematicides compared to the control. However, the application of hymexazol did not yield a statistically significant difference in the egg masses index compared to the control, a finding which may be attributed to its potentially limited penetrability through the eggshell barrier. Overall, this study has demonstrated that all four nematicides effectively suppress M. enterolobii in sweetpotato, and this is the first report on the nematicidal activity of cyclobutrifluram and hymexazol against M. enterolobii.

Qingru Niu,1– 3,&ast; Chuanmiao Lin,1– 3,&ast; Shuqing Yang,1– 3 Shuxuan Rong,1– 3 Junbin Wei,1– 3 Tingting Zhao,1– 3 Yingying Peng,1– 3 Zhilan Cheng,1– 3 Yunyi Xie,1– 3 Yan Wang1– 3 1Hospital of Stomatology, Guanghua School of Stomatology, Guangzhou, People’s Republic of China; 2Sun Yat-Sen University, Guangzhou, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunyi Xie; Yan Wang, Email xieyy59@mail2.sysu.edu.cn; wang93@mail.sysu.edu.cnPurpose: Periodontitis is a chronic infectious disease characterized by progressive inflammation and alveolar bone loss. Forkhead box O1 (FoxO1), an important regulator, plays a crucial role in maintaining bone homeostasis and regulating macrophage energy metabolism and osteogenic differentiation of mesenchymal stem cells (MSCs). In this study, FoxO1 was overexpressed into small extracellular vesicles (sEV) using engineering technology, and effects of FoxO1-overexpressed sEV on periodontal tissue regeneration as well as the underlying mechanisms were investigated.Methods: Human periodontal ligament stem cell (hPDLSCs)-derived sEV (hPDLSCs-sEV) were isolated using ultracentrifugation. They were then characterized using transmission electron microscopy, Nanosight, and Western blotting analyses. hPDLSCs were treated with hPDLSCs-sEV in vitro after stimulation with lipopolysaccharide, and osteogenesis was evaluated. The effect of hPDLSCs-sEV on the polarization phenotype of THP-1 macrophages was also evaluated. In addition, we measured the reactive oxygen species (ROS) levels, adenosine triphosphate (ATP) production, mitochondrial characteristics, and metabolism of hPDLSCs and THP-1 cells. Experimental periodontitis was established in vivo in mice. HPDLSCs-sEV or phosphate-buffered saline (PBS) were injected into periodontal tissues for four weeks, and the maxillae were collected and assessed by micro-computed tomography, histological staining, and small animal in vivo imaging.Results: In vitro, FoxO1-overexpressed sEV promoted osteogenic differentiation of hPDLSCs in the inflammatory environment and polarized THP-1 cells from the M1 phenotype to the M2 phenotype. Furthermore, FoxO1-overexpressed sEV regulated the ROS level, ATP production, mitochondrial characteristics, and metabolism of hPDLSCs and THP-1 cells in the inflammatory environment. In the in vivo analyses, FoxO1-overexpressed sEV effectively promoted bone formation and inhibited inflammation.Conclusion: FoxO1-overexpressed sEV can regulate osteogenesis and immunomodulation. The ability of FoxO1-overexpressed sEV to regulate inflammation and osteogenesis can pave the way for the establishment of a therapeutic approach for periodontitis. Keywords: periodontal ligament stem cells, small extracellular vesicles, periodontitis, bone homeostasis, mitochondrial function

Considering the dual requirements of stability and low carbon, integrating clean coal power with carbon capture, utilization and storage (CCUS) and combining new energy power generation with energy storage have become the inevitable trends of China’s power industry. This study investigates the typical cases regarding clean coal power, CCUS, new energy power generation, and energy storage in China and abroad, analyzing the trend of technological development. A levelling cost model is used to measure the economical efficiency and changes of “clean coal power + CCUS” in three stages: current stage, technological breakthroughs, and commercial application. The competitiveness of “clean coal power + CCUS” is evaluated by comparing it with the “new energy + energy storage” mode from three dimensions: economical efficiency, stability, and security. The results indicate that technological breakthroughs and commercialization of CCUS will reduce the cost of “clean coal power + CCUS” by 30.3%−77.6%. When the cost of CCUS is lower than 550 CNY/t CO2, “clean coal power + CCUS” is more competitive than the “new energy + energy storage” mode. When the cost of CCUS is lower than 150 CNY/t CO2, the cost of “clean coal power + CCUS” will be lower than that of “new energy + energy storage”. Moreover, advantageous technical routes and application scenarios of “clean coal power + CCUS” are calculated and analyzed based on the competitiveness and synergy of “clean coal power + CCUS” and “new energy + energy storage”. The breakthrough directions and technical path of zero-carbon clean coal power are proposed from the aspects of improving the complementarity of clean coal power, enhancing the competitiveness of “clean coal power + CCUS”, and promoting the optimal combination of coal power and new energy. Furthermore, the following suggestions are proposed to promote the development of lowcarbon clean coal: (1) clarifying the preferential technology route, (2) strengthening the research and development of transformative and disruptive technologies, (3) improving the peak shaving capability of clean coal-fired power units, (4) promoting the coupling and coordinated development of coal-fired power and new energy, and (5) establishing a high-end composite talent support system.

Objective·To analyze the anatomical and macroscopic characteristics of the pterygopalatine suture (PPS) in Chinese population using cone-beam computed tomography (CBCT) technology, and to preliminarily investigate its developmental pattern and its association with the correction of maxillary underdevelopment.Methods·A total of 134 CBCT images, taken from July to August 2023 at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, were categorized into six age groups. The PPS landmarks were utilized to determine the overall transverse position (XPPS), sagittal position (YPPS), insertion angle (IAP), insertion width of the pyramidal process (IWP), and insertion depth of the pyramidal process (IDP). The pterygomaxillary junction was identified through multiplanar observations. Regression analysis was performed to assess the correlation of these parameters with age and gender, and pairwise comparisons were made to determine the stable age range for parameter changes. Paired t-tests and paired chi-squared tests were conducted to analyze the bilateral parameter differences.Results·Results showed that YPPS and IDP did not exhibit significant correlation with age, whereas XPPS, IAP, IWP, and the incidence of pterygomaxillary fusion were significantly positively correlated with age (P

Jing Kong,1,&ast; Jiabin Lai,2– 4,&ast; Min Wang,5,&ast; Yi Xie,1 Haifei He,6 Jiayu Gu,7 Tao Pan,6 Zhiqiang Lu,8 Lifeng Jiang3,4 1Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Orthopedic Research Institute of Zhejiang University, Hangzhou, People’s Republic of China; 4Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, People’s Republic of China; 5Digestive Endoscopy Department, The First Affiliated Hospital with Nanjing Medical University & Jiangsu Province Hospital, Nanjing, People’s Republic of China; 6Department of Breast Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 7Jiangsu Institute of Metrology, Nanjing, People’s Republic of China; 8Department of Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lifeng Jiang; Zhiqiang Lu, Email jianglifeng@zju.edu.cn; taiyi1981@126.comBackground: Chemodynamic therapy (CDT) faces challenges of low catalytic ion efficiency and ROS production. We developed a ROS nano-bomb, Cu/ZIF-8@GA-Fe, to address these issues.Methods: The nano-bomb was synthesized by doping copper into ZIF-8 and assembling Fe3+ and gallic acid (GA). It was tested for reactive oxygen species (ROS) generation in acidic conditions and its photothermal properties.Results: In an acidic micro environment, Cu/ZIF-8@GA-Fe effectively released Fe3+ and Cu2+, depleting GSH and generating ROS. The GA-Fe coating provided photothermal heat and was used to enhance Fenton reactions via dual ions for increasing ROS production. In vivo and in vitro experiments, Cu/ZIF-8@GA-Fe inhibited tumor growth with minimal side effects.Conclusion: Cu/ZIF-8@GA-Fe shows promise for safe and effective CDT, offering a synergistic approach to tumor therapy.Keywords: reactive oxygen species, nano-bomb, combination therapy, chemodynamic therapy, photothermal therapy

【Objective】In order to solve the problem of the limited bandwidth of polarization insensitive optical power splitter, an ultra-broadband polarization insensitive optical power splitter based on Silicon Nitride (Si3N4) waveguide is proposed.【Methods】The ultra-broadband polarization insensitive optical power splitter is designed based on adiabatic coupling Si3N4 waveguide.Optical bandwidth of 300 nm (from 1 400 ~ 1 700 nm) is demonstrated for both Transverse Electric (TE) and Transverse Magnetic (TM) modes.【Results】Over the entire optical bandwidth, the losses for TE and TM mode are less than 0.10 and 0.15 dB, respectively.The footprint of the proposed ultra-broadband polarization insensitive optical power splitter is only 60.00 μm×2.75 μm, which means that the optical power splitter can be used for large-scale integration.Furthermore, the relationship between the performance and the structure parameters of the proposed optical power splitter is studied.【Conclusions】The results show that the performance of the optical power splitter maintains almost unchanged by varying the structure parameters with ±50 nm.In other words, the optical power splitter possesses large fabrication tolerance which can be easily fabricated.

Enterococcus faecalis is the main pathogen causing refractory apical periodontitis (RAP). This bacterium can tolerate harsh environments and trigger periapical immune inflammatory responses that result in persistent infection inside and outside the root canal. Adhesion to the dentin wall of root canals and the subsequent formation of biofilms significantly enhances the drug resistance and anti-erosion ability of Enterococcus faecalis, which is the key factor mediating its pathogenesis. The adhesion of Enterococcus faecalis to dentin involves non-specific adhesion and specific adhesion, and the latter is mediated by adhesion-related virulence factors, mainly including the adhesin of collagen from enterococci (Ace), extracellular surface protein (Esp), gelatinase (GelE), serine protease (SprE), endocarditis and biofilm associated pilus (Ebp) and aggregation substance (AS), which is regulated by multiple two-component systems. The two-component system Fsr can promote the expression of gelE and sprE when the cell population density increases. GelE can further reduce Ace, while the two-component system GrvRS directly downregulates ace expression in response to the serum environment. The two-component systems CroRS and WalRK may also promote and inhibit the expression of various virulence factors, including ace and gelE, thus affecting the adhesion of Enterococcus faecalis. In addition, the mechanochemical preparation and the internal environment of the root canal can also influence the adhesion of Enterococcus faecalis to dentin. Avoiding the introduction of Enterococcus faecalis and using adhesion-interfering medications during root canal treatment can effectively prevent the adhesion of Enterococcus faecalis, and a variety of activated irrigation protocols can also be effective at increasing the clearance of Enterococcus faecalis from the root canal. The design of rational drugs targeting key factors involved in and regulators of the adhesion of Enterococcus faecalis to dentin is expected to provide new ideas and strategies for root canal infection control. The present paper reviews the adhesion of Enterococcus faecalis to dentin and its influencing factors.

Background Wrist motor dysfunction is a common sequela at post-stroke, and the wrist has an important role in improving hand practicality. Therefore, improving the range of motion of the wrist can effectively promote the activities of daily life in post-stroke patients. Although repetitive peripheral magnetic stimulations (rPMS) have been shown to have a significant effect on improving the range of motion of the wrist, the therapeutic effect of different stimulation sites still needs to be further explored. Objective To investigate the effect of rPMS on wrist extensor muscle and radial nerve for the motor function of wrist of subacute stroke patients. Methods A total of 60 subacute stroke patients with wrist motor dysfunction admitted to Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine from October 2022 to October 2023 were selected as the study subjects. The included patients were randomly divided into control group (20 cases), muscle stimulation group (20 cases) and nerve stimulation group (20 cases) by simple randomized grouping method using a random number table. Patients in all the three groups received routine rehabilitation training, and those in the muscle stimulation group and nerve stimulation group were additionally managed by rPMS on the wrist extensor muscle and the radial nerve, respectively. Before and after the interventions for 10 times of rPMS, integrated electromyography (iEMG), root mean square (RMS) and median frequency (MF) on the surface of the wrist extensor muscle, the Fugl-Meyer Assessment for upper extremity (FMA-UE), the Action Research Arm Test (ARAT) and the modified Barthel Index (MBI) were measured to assess the upper limb function of the affected side. Results During the intervention period, there were 2 cases of data loss due to voluntary withdrawal or forced termination of the trial, and finally 20 cases were included in the control group, 19 cases in the muscle stimulation group, and 19 cases in the nerve stimulation group. There were no significant differences in iEMG, RMS and MF of wrist extensor muscle among three groups before treatment (P>0.05). After treatment, iEMG, RMS and MF of wrist extensor muscle in muscle stimulation group and nerve stimulation group were significantly higher than those of control group (P0.05). After treatment, FMA-UE, ARAT and MBI scores in muscle stimulation group and nerve stimulation group were significantly higher than those of control group (P

Sleep disorder is a common complication of stroke, which not only negatively affects the patients’ quality of life, but also affects the rehabilitation process of stroke disease. There are many causes of post-stroke sleep disorders, including clinical medication, patients' own psychological factors, pathological damage, etc. From the perspective of Traditional Chinese medicine nursing and analysis of actual situation of patients with post-stroke sleep disorders, this study reviewed the studies on Traditional Chinese Medicine nursing for patients with sleep disorder after stroke, and provided reference for clinical decision making and nursing practice. (睡眠障碍是脑卒中患者较为常见的一种并发症, 不仅影响患者生活质量, 且不利于脑卒中后期康复。脑卒中后患者并发睡眠障碍与临床用药、患者自身心理因素、病理损害等有关。本研究从中医护理的角度进行分析, 结合脑卒中后睡眠障碍患者实际情况, 就脑卒中后睡眠障碍患者的中医护理研究现状进行综述, 旨在为临床制定相关干预方案提供参考与借鉴。)

Objective The formation of monsoon climates is attributed to the seasonal reversal of wind direction and precipitation caused by the difference in thermal capacity between land and ocean. Asia is recognized as the most prominent region globally, with monsoon climates, that affect the largest population. The heavy rainfall accompanying monsoons can result in various secondary disasters, substatially jeopardizing human safety and productivity in the region. Consequently, comprehending the formation process of the Asian monsoon holds paramount importance. Methods This study aim to employ geological concepts to establish a connection between the past and present, providing an overview of the components of Asian monsoons, identifying the primary factors influencing their formation and evolution, and summarizing research progress on the South Asian and East Asian monsoons based on sediment records from key Asian locations. Results The findings indicate that during the Cenozoic, the collision between the Indian Plate and the southern margin of the Asian continent altered the distribution of land and sea in Asia. Consequently, the Tibetan Plateau experienced initial uplift, contributing to the emergence of monsoon climates in South Asia and East Asia. However, at this stage, the East Asian region was still primarily influenced by the planetary wind system, and the East Asian monsoon was in its early stages, predominantly restricted to the southern margin of the South China Plate in a localized manner. In contrast, the South Asian Monsoon covered a relatively extensive area. This discrepancy may be attributed to the delayed opening of marginal seas in the East Asian region compared to the relatively earlier occurrence of land and sea distribution in South Asia. However, as the Tibetan Plateau continued to uplift and approach its current altitude during the middle to late Cenozoic, the Asian monsoon entered a strengthening phase, notably impacting regional geological evolution processes. Since the middle to late Cenozoic, the development of the North and South Polar ice caps and the upliftment of the Tibetan Plateau have controlled the Asian monsoon, leading it to undergo multiple stable periods of development. Conclusion The development and evolution of the East Asian and South Asian monsoons are mainly driven by the distribution of sea and land in the Asia, the upliftment of the Tibetan Plateau and the global climate change during the Cenozoic. Significance These findings provide valuable insights into the scientific and rational utilization of the Asian monsoon for conducting systematic Earth science research in Asia.

Overhead transmission lines are the significant component of electric power system, where the over current can be coupled with the transient electromagnetic field or excitations (such as high-altitude electromagnetic pulse). As the coupling path of strong electro-magnetic interference, overhead transmission lines cause serious interference to the power system. Among the existing modelling methods, the classical transmission line theory may generate large error when dealing with the high-frequency coupling problem, where the cross dimension of the transmission line is not electrically small. Numerical full-wave method (such as moment of method) which relies on the grid subdivision with low efficiency when dealing with long transmission lines. Moreover, the number of cables is usually large in electric power system, and the ground are considered as the lossy ground. Therefore, to address the above mentioned problems, an asymptotic method is proposed to calculate the high-frequency coupling current along overhead transmission lines in electric power system. Based on the asymptotic theory with high calculation efficiency, the scattering and reflection process are introduced to quantify higher-order model components. In addition, the arbitrary number of wires, arbitrary parameters of the ground and different excitations are considered to derivate the current expression. Finally, the validity and reliability of the proposed method are tested using the full-wave simulation and antenna irradiation experiment. The proposed method can quickly calculate high-frequency coupling current, which can provide theoretical basis and data support for protection and electromagnetic effect study of overhead transmission lines.

Minmin Jiang,1,&ast; Yongxia Xie,2,&ast; Ping Wang,1 Mengyu Du,3 Ying Wang,4 Shuxun Yan1 1Department of Endocrinology, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 3The First Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 4Department of International Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuxun Yan; Ying Wang, Email ysx982001@163.com; wangying56994@126.comAbstract: Fibrosis leads to organ failure and death, which is the final stage of many chronic diseases. Triptolide (TPL) is a terpenoid extracted from the traditional Chinese medicine Tripterygium wilfordii Hook. F (TwHF). Triptolide and its derivatives (Omtriptolide, Minnelide, (5R)-5-hydroxytriptolide) have been proven to have a variety of pharmacological effects. This study comprehensively reviewed the antifibrotic mechanism of TPL and its derivatives, and discussed the application of advanced nanoparticles (NPs) drug delivery system in the treatment of fibrotic diseases by TPL. The results show that TPL can inhibit immune inflammatory response, relieve oxidative stress and endoplasmic reticulum stress (ERS), regulate collagen deposition and inhibit myofibroblast production to play an anti-fibrosis effect and reduce organ injury. A low dose of TPL has no obvious toxicity. Under pathological conditions, a toxic dose of TPL has a protective effect on organs. The emergence of TPL derivatives (especially Minnelide) and NPs drug delivery systems promotes the anti-fibrosis effect of TPL and reduces its toxicity, which may be the main direction of anti-fibrosis research in the future.Keywords: triptolide, derivatives, anti-fibrosis, nanoparticles

Yuying Ge,1,&ast; Yuepeng Xie,2,&ast; Junlei Chai,3,&ast; Weifeng Ji,4,&ast; Xiulong Lou,1 Kun Tian,2 Ronghua Bao,3 Chengliang Wu,1 Hongfeng Ruan1 1Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, People’s Republic of China; 2The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Hangzhou Fuyang Hospital of TCM Orthopedics and Traumatology, Hangzhou, People’s Republic of China; 4Department of Orthopaedics, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongfeng Ruan; Chengliang Wu, Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Fax +86 571 86613684, Email rhf@zcmu.edu.cn; wcl@zcmu.edu.cnBackground: Intervertebral disc (IVD) degeneration (IVDD) is highly prevalent among the elderly population and stands as a leading cause of low back pain. Our prior studies have highlighted the therapeutic potential of Liuwei Dihuang decoction (LWDHD) and its component Cornus officinalis (CO)-derived compounds in alleviating IVDD and osteoarthritis, suggesting beneficial effects of CO in treating degenerative osteoarthropathies. However, uncertainty remains regarding the optimal CO dosage within LWDHD and its potential mechanism for effectively treating IVDD.Objective: To ascertain the optimal dosage of CO within LWDHD for enhancing its therapeutic efficacy in treating IVDD, through a comparison of its effects across varied dosages using a mouse IVDD model.Methods: Eight-week-old male C57BL/6J mice were subjected to a lumbar spine instability surgery to induce an IVDD model and received a modified LWDHD formulation containing varied dosages of CO (original dose of CO, or 5- or 10-time dose of CO (referred to as 1 × CO, 5 × CO, and 10 × CO)) for 8 weeks. The therapeutic efficacy on IVDD was evaluated through changes in lumbar spine function, histopathological morphology, extracellular matrix metabolism, nucleus pulposus cell viability, sensory nerve ingrowth, and nucleus pulposus (NP) cell pyroptosis.Results: Augmenting CO levels in LWDHD led to a dose-dependent increase in the levels of CO-sourced active compounds in the plasma of mice. The modified LWDHD formulations, particularly the 5 × CO, exhibited a favorable pharmacological effect on lumbar function, structural integrity, ECM composition, NP cell viability, and sensory nerve ingrowth. Importantly, all 3 formulations notably mitigated NP cell pyroptosis by activating NRF2/KEAP1 pathway, with the 5 × CO formulation exhibiting superior efficacy. Additionally, a comprehensive score analysis indicated that 5 × CO formulation achieved the highest score.Conclusion: These data underscore that elevating the dosage of CO to a specific threshold can enhance the effectiveness of LWDHD in treating IVDD.Keywords: intervertebral disc degeneration, liuwei dihuang decoction, nucleus pulposus cell, pyroptosis, Cornus officinalis

AIM: To compare the clinical effectiveness of using multifocal defocus spectacle lenses, orthokeratology lenses, and single-vision spectacle lenses in patients with myopia and small-angle intermittent exotropia.METHODS: This retrospective study included 150 patients aged 8-15 years with basic intermittent exotropia, strabismus of -10△ to -20△ prism diopters(D)(block lenses), and spherical equivalents of -1.00 to -5.50 D, who visited our hospital from June 2021 to September 2022. They were selected and divided into three groups on a voluntary basis: the HAL group(50 patients with multifocal myopia defocus spectacle lenses), the OK lens group(50 patients with nighttime orthokeratology lenses), and the SVL group(50 patients with regular single-vision spectacle lenses). After wearing the lenses consistently, changes in axial length, prism diopters with the naked eye and lenses(prism at 33 cm), positive fusional vergence of blurred points, and near stereopsis were observed and compared among groups before intervention and after 1 a. The Newcastle control score(NCS)was used to evaluate the eye position control ability of the patients in the three groups.RESULTS: Before the intervention, the axial lengths of the HAL, OK lens, and SVL groups were 24.83±0.91, 24.93±0.97, and 24.98±0.68 mm, respectively(P>0.05). After 1 a, the axial lengths of the three groups were 25.02±0.90, 25.18±0.97, and 25.45±0.65, respectively(P0.05). After 1 year, near stereopsis in the groups were 76.00″±20.40″, 81.20″±18.91″, and 100.60″±51.41″, respectively(P0.05), and it was 17.10±2.02, 13.12±1.41, and 13.26±2.45, respectively, after 1 a(P

Efflux pumps play a crucial role in the development of antibiotic resistance. The aim of this study was to investigate the relationship between efflux pump gene expression and resistance gene mutations in Helicobacter pylori. Twenty-six clinical strains with varying resistance characteristics were selected for further experiment. Seven susceptible strains were induced to become resistant, and the expression of efflux pump genes and point mutations were recorded. Four susceptible strains were selected to undergo candidate mutation construction, and changes in efflux pump gene expression were detected. Efflux pump knockout strains were constructed, and their effects on preventing and reversing antibiotic resistance gene mutations were assessed. Results showed that the expression of efflux pump genes hefA and hefD was significantly higher in the multidrug-resistant group compared to other groups. During the process of antibiotic-induced resistance, efflux pump gene expression did not exhibit a steady increase or decrease. Strains with the A2143G or A2142G point mutations in 23S rRNA exhibited lower hefA gene expression. Strains with mutations at 87K/91N, 87N/91 G, 87K/91D, or 87N/91Y in gyrA and the 194insertA mutation in rdxA showed higher hefA gene expression compared to the wild-type strain. During the process of antibiotic-induced resistance, the strain with the knockout of the efflux pump gene hefA developed mutations in the 23S rRNA, gyrA, or rdxA genes later compared to the wild-type strain. Knockout of the efflux pump gene could reverse the phenotypic resistance to clarithromycin or metronidazole in some strains but had no effect on reverse resistance gene mutation. This study suggested that different resistance gene point mutations may have varying effects on efflux pump gene expression. Knockout of the efflux pump gene can delay or prevent antibiotic resistance gene mutations to some extent and can reverse phenotypic resistance to clarithromycin and metronidazole in certain strains.

ObjectiveBy computerized analysis of writing ability assessment data, to accurately assess the quality and proficiency of writing among primary school students, and to provide data support for accurate screening and assessment of those with writing difficulties.MethodsA cross-sectional study was conducted to evaluate the writing ability of 1 085 students from grade 1 to grade 6 in the Experimental Primary School Affiliated to Minjiang Teachers College, Fuzhou, Fujian Province, using the smart handwriting analysis recognition platform (SHARP). The assessment indicators included writing speed, writing control, writing integration, time-on-paper ratio, accuracy of writing outcomes, and overall writing performance.ResultsGirls outperformed boys in writing control, writing integration, time-on-paper ratio, accuracy of writing outcomes, and overall writing performance (PPPPP>0.05). 2) In terms of writing control ability, the overall trend of grades 1 to 6 showed a gradual development, with the performance of writing control ability in grade 3 being better than that in grade 2 (PPP>0.05). 3) In terms of the writing integration ability and time-on-paper ratio, as the grades increased, the higher grades developed better than the lower grades between adjacent grades 1 to 4 (PP>0.05). 4) in terms of the accuracy of writing outcomes, grade 2 was better than grade 1 (PPP>0.05); 5) In terms of overall writing performance, grade 2 performed better than grade 1 (PP>0.05). There was a significant negative correlation between writing control, writing integration and writing outcome accuracy and overall writing performance (r>-0.5), a highly positive correlation between time-on-paper ratio and overall writing performance (r=0.575), and a highly negative correlation between time-on-paper ratio and writing integration (r=-0.999). Writing outcome accuracy explained only 39.1% of the variation in overall writing performance, and writing outcome accuracy, time-on-paper ratio, writing control, and writing integration together explained 71.8% of the variation in overall writing performance.ConclusionAt the primary level, girls generally outperform boys in writing ability, but sex and dominant hand still do not predict overall performance in writing. As the grades increase, students' writing abilities tend to mature. Writing speed reaches a plateau around grades 4-5, writing control develops more rapidly in grades 2-3 and 4-5, and writing integration and time-on-paper ratio enters a relative stable plateau after about grade 4. Accuracy of writing outcomes alone is not suitable as a predictor of overall writing performance; writing control, writing integration, and time-on-paper ratio have strong effects on overall writing performance and can be combined as predictors of overall writing performance.

ObjectiveFrom the perspective of colorectal cancer stem cells，the purpose of this study was to explore the effect and its mechanism of Spica Prunellae on the proliferation and stemness of colorectal cancer cells based on Notch signaling pathway.MethodsColorectal cancer SW480 cells were cultured in vitro. When the cells were in logarithmic growth phase, they were randomly divided into control group, 0.1 mg/mL group, 0.2 mg/mL group and 0.4 mg/mL group. The control group did not receive drug intervention; the other three groups were added with 0.1 mg/mL, 0.2 mg/mL and 0.4 mg/mL Spica Prunellae solution, respectively. Meanwhile, DMSO in each group was supplemented to the same amount. After 24 hours of intervention, the subsequent experiments were performed. The cell growth morphology and density were observed by inverted microscope. The number of viable cells was detected by 0.4% Trypan blue staining and cell survival rate was calculated. The proliferation inhibition rate of colorectal cancer cells was detected using Cell Counting Kit-8 (CCK8) assay. Flow cytometry was used to detect the proportion of stem cells in colorectal cancer cells. The self-renewal ability of colorectal cancer cells was detected by sphere formation assay. Western blot method was used to detect the relative expression of c-Myc, CD44, CD133, SOX2 and Notch pathway-related proteins Notch1 and Hes1 in colorectal cancer cells.ResultsCompared with the control group, the proliferation and viability of colorectal cancer SW480 cells in the 0.1, 0.2, and 0.4 mg/mL groups were significantly inhibited with the increase of Spica Prunellae concentration (PPPP

[Objective] This study was aimed to investigate the effects of organic manure replacing chemical fertilizer with equal nitrogen under different nitrogen application rates on the growth, yield and water-fertilizer use efficiency of spring maize in the dry zone of northern Shaanxi. [Methods] Multiple regression analysis and three-dimensional fitting models were used to establishing an optimal nitrogen management model for spring maize cultivation in northern Shaanxi. In this experiment, three nitrogen application levels (240, 180, 120 kg/hm2 for N1, N2, N3, respectively) and five organic manure replacing chemical fertilizer with equal nitrogen ratios (R0, R12.5, R25, R37.5, R50 for 100% chemical fertilizer nitrogen, 12.5% organic fertilizer nitrogen+87.5% chemical fertilizer nitrogen, 25% organic fertilizer nitrogen+75% chemical fertilizer nitrogen, 37.5% organic fertilizer nitrogen+62.5% chemical fertilizer nitrogen, 50% organic fertilizer nitrogen+50% chemical fertilizer nitrogen, respectively), a total of 15 treatments. During the main reproductive period of spring maize, spring maize growth and yield and yield components were measured, and water consumption (ET), water use efficiency (WUE), nitrogen fertilizer partial productivity (NPFP) and economic benefits were calculated. [Results] The Logistic function had a high fit for dry matter accumulation in spring maize, the R12.5 treatment delayed the start, the end and the appearance of the maximum value of the period of rapid dry matter accumulation, and the N2 treatment enhanced the maximum daily growth rate of dry matter accumulation. Nitrogen application and replacement ratio significantly affected dry matter accumulation, yield and components, ET, NPFP and economic efficiency of spring maize (p

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), remains one of the leading causes of fatal infectious diseases worldwide. The only licensed vaccine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), has variable efficacy against TB in adults. Insufficiency of immune cell function diminishes the protective effects of the BCG vaccine. It is critical to clarify the mechanism underlying the antimycobacterial immune response during BCG vaccination. Macrophage mannose receptor (MR) is important for enhancing the uptake and processing of glycoconjugated antigens from pathogens for presentation to T cells, but the roles of macrophage MR in the BCG-induced immune response against M.tb are not yet clear. Here, we discover that macrophage MR deficiency impairs the antimycobacterial immune response in BCG-vaccinated mice. Mechanistically, macrophage MR triggers JAK-STAT1 signaling, which promotes antigen presentation via upregulated MHC-II and induces IL-12 production by macrophages, contributing to CD4+ T cell activation and IFN-γ production. MR deficiency in macrophages reduces the vaccine efficacy of BCG and increases susceptibility to M.tb H37Ra challenge in mice. Our results suggest that MR is critical for macrophage antigen presentation and the antimycobacterial immune response to BCG vaccination and offer valuable guidance for the preventive strategy of BCG immunization.

Strategic minerals are the cornerstone of national security and stable development. China’s strategic mineral imports are highly dependent on maritime transport, and ensuring smooth maritime routes is crucial for safeguarding the security of strategic mineral imports. This study analyzes the overall pattern of China’s strategic mineral imports and maritime routes. Taking the iron ore maritime import network as an example, the study evaluates the importance and failure impacts of key maritime routes, summarizes the risk sources of important maritime routes, and proposes corresponding security strategies. The research finds that China’s strategic mineral imports are highly dependent on maritime routes. Based on the case study of iron ore maritime transport, the importance and failure impacts of maritime routes are identified. It is suggested to build differentiated and refined response strategies, focus on the protection of the Cape of Good Hope and the Lombok Strait transport corridor network, and pay attention to the safe navigation of large vessels. The risks of maritime routes for China’s strategic minerals mainly come from three aspects: navigational passages, international disputes and war threats, and non-traditional security issues. In response, multi-domain response strategies can be implemented, including building multiple strategic pivot nodes, constructing a multidimensional early warning system and an alternative route response mechanism, strengthening the construction of cross-border rail – sea intermodal transport corridors, conducting preventive diplomatic work, improving the maritime security system, and implementing hierarchical and differentiated risk-response measures.

Combination of metal matrix materials with carbon quantum dots (CQDs) can not only optimize the property of metal matrix materials, but also produce novel material systems with ultra-high performance or superior comprehensive performance. The excellent electrical, mechanical, and thermal characteristics of CQDs can compensate for some intrinsic defects of the metal matrices to improve the composite properties. The various interfaces formed through the different degrees of CQDs dispersion in the metal matrices are essential in the mechanism of the composite performance improvement. In this review, the research progress and results of CQDs in metal matrix composites are discussed and summarized, including the recent preparation methods of CQDs and carbon nanostructure-reinforced metal matrix materials, as well as the influences of the preparation methods on the material structures and properties. In addition, by focusing on the interfaces between CQDs and metal matrices in composite materials, the performance improvement and reinforcement mechanisms of the CQD-modified metal matrix composites are described from mechanical, electrical, and thermal aspects. Further studies on CQDs in metal matrix composites are still required to provide theoretical guidance for the preparation of CQDs-reinforced metal matrix composites with intensity and ductility above the average.

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

Wanxin Shi,1,2,&ast; Huiwen Yan,1,&ast; Xiaoli Liu,1 Lihua Yu,1 Yuqing Xie,1 Yuan Wu,1 Yuling Liang,1 Zhiyun Yang1 1Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2First Clinical Medical College, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiyun Yang, Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, People’s Republic of China, Tel/Fax +86-10-84322148, Email yangzhiyun2016@163.comPurpose: Portal vein tumor thrombosis (PVTT) is one of the hallmarks of advanced Hepatocellular carcinoma (HCC). Platelet (PLT) function parameters and CD8+T cells (CD8+Ts) play an important role in HCC progression and metastasis. This study is committed to establishing an efficient prognosis prediction model and exploring the combined effect of PLT and CD8+Ts on PVTT prognosis.Patients and Methods: This retrospective study collected 932 HCC patients with PVTT from 2007 to 2017 and randomly divided them into a training cohort (n = 656) and a validation cohort (n = 276). We performed multivariable Cox and Elastic-net regression analysis, constructed a nomogram and used Kaplan–Meier survival curves to compare overall survival and progression-free survival rates in different substrata. Relationships between indicators involved were also analyzed.Results: We found tumor number, size, treatment, PLT, γ-glutamyl transferase, alpha-fetoprotein, mean platelet volume, and CD8+Ts were related to the 5-year OS of patients with PVTT, and established a nomogram. The area under the receiver operating characteristic curve (AUCs) for predicting the 1-year OS rates were 0.767 and 0.794 in training and validation cohorts. The calibration curve and decision curve indicated its predictive consistency and strong clinical utility. We also found those with low PLT (< 100&ast;10^9/L) and high CD8+Ts (> 320 cells/μL) had a better prognosis.Conclusion: We established a well-performing prognostic model for PVTT based on platelet functional parameters and CD8+Ts, and found that PT-8 formed by PLT and CD8+Ts was an excellent predictor of the prognosis of PVTT.Keywords: hepatocellular carcinoma, portal vein tumor thrombus, platelet, CD8+T cells counts, prognostic model, correlation analysis

Liyun Zou,1,&ast; Qiufeng Wei,1,&ast; Sining Pan,1,&ast; Fei Xiao,1,2 Yage Jiang,1 Yu Zhong,1 Yubo Xie1,3 1Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yubo Xie; Yu Zhong, Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, Tel +86 13977121557 ; +86 15177929679, Email xybdoctor@163.com; zzlugl@163.comBackground: Perioperative anesthetic management of patients with diabetic foot undergoing surgical treatment is challenging due to their poor cardiovascular health status. According to previous literature, general anesthesia and peripheral nerve block have their own advantages and disadvantages for such patients. We reported the effect of these two anesthesia techniques on perioperative hemodynamics and prognosis in these patients.Methods: This study employed a prospective randomized controlled design, where patients meeting the inclusion criteria were assigned to two groups: the general anesthesia group (GA group) and the peripheral nerve block group (PNB group). The primary outcomes were the differences in intraoperative hemodynamic stability and the incidence of postoperative complications between the two groups. The second outcomes were postoperative numerical rating scale scores, analgesic drug remedies, postoperative sleep conditions monitored by sleep bracelets and health status assessed by EQ-5D-5 L scores.Results: One hundred and nine subjects were enrolled in this study, including 54 in the GA group and 55 in the PNB group. The baseline parameters of the two groups were comparable. The GA group exhibited a significantly higher incidence of hypotension, and Colloid intake and total fluid intake were significantly higher in the GA group than in the PNB group. Additionally, a larger proportion of patients in the GA group. The scores of postoperative pain during the 48 hours after surgery were significantly higher, and more patients needed tramadol for postoperative analgesia during the 24 h after surgery in the GA group than in the PNB group. Patients in the PNB group slept better, first feeding time, earlier out-of-bed activity and earlier discharge from the hospital, compared to the GA group. However, there was no obvious difference in postoperative complications between the two groups except pharyngeal pain.Conclusion: Peripheral nerve block is a better option in patients with diabetes undergoing elective below-knee surgery than general anesthesia.Keywords: diabetic foot, general anesthesia, peripheral nerve block, hemodynamic, postoperative pain, postoperative complication

Yi Yang,1 Jingxian Wang,1 Qing Su,1 Jinhuan Yang,2,3 Zhiyuan Bo,2,3 Chongming Zheng,2,3 Yitong Xie,2,3 Kaiwen Chen,2,3 Juejin Wang,1 Gang Chen,2,3 Yi Wang1 1Department of Epidemiology and Biostatistics, School of Public Health, Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of China; 2Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of China; 3Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of ChinaCorrespondence: Yi Wang, Department of Epidemiology and Biostatistics, School of Public Health, Wenzhou Medical University, Nanliu Road, Chashan Street, Ouhai District, Wenzhou City, Zhejiang Province, 325035, People’s Republic of China, Fax +86(577)-86699-358, Email wang.yi@wmu.edu.cn Gang Chen, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Shangcai Village, Nanbaixiang Street, Ouhai District, Wenzhou City, Zhejiang Province, 325035, People’s Republic of China, Fax +86(577)-55579-555, Email chen.gang@wmu.edu.cnBackground: Primary liver cancer (PLC) is a fatal malignancy, sleep quality and gut microbiota were shown to be associated with PLC. However, the mechanism of how sleep quality affects PLC is unclear. This study aims to investigate the mediation/moderation effects of gut microbiota on sleep quality and the occurrence of PLC.Methods: The causality of sleep quality and the occurrence of PLC was detected through the Mendelian randomization (MR) analysis based on the data including 305,359 individuals (Finland Database) and 456,348 participants (UK Biobank). The primary method used for MR analysis was inverse-variance weighted analysis. Gut microbiota’ mediation/moderation effects were uncovered in the case–control study including 254 patients with PLC and 193 people with benign liver diseases through the mediation/moderation effect analyses. People’s sleep quality was evaluated through the Pittsburgh sleep quality index (PSQI).Results: Poor sleep quality could lead to PLC through the MR analysis (P = 0.026). The case–control study uncovered that Actinobacteria had mediation effects on the relationship between PSQI score, self-sleep quality, and the occurrence of PLC (P = 0.048, P = 0.046). Actinobacteria and Bifidobacterium could inhibit the development of PLC caused by short night sleep duration (P = 0.021, P = 0.022). Erysipelotrichales could weaken the influence of daytime dysfunction on PLC (P = 0.033). Roseburia modulated the contribution of nocturnal insomnia and poor sleep quality to PLC (P = 0.009, P = 0.017).Conclusion: Poor sleep quality was associated with PLC. Gut microbiota’ mediation/moderation effects on poor sleep quality and the occurrence of PLC prompted an insightful idea for the prevention of PLC.Keywords: primary liver cancer, sleep quality, gut microbiota, Mendelian randomization, mediation/moderation effect