Chemokines and their receptors play crucial roles in nervous system diseases,among which the CXC chemokine receptor 3(CXCR3)is an important mediator of intercellular communication.CXCR3 not only participates in inflammatory chemotaxis and malignant behaviors of tumor cells but also regulates the neurologic diseases.CXCR3 and its ligands directly or indirectly contribute to neuroinflammation and neuroimmunity,and potentially serve as therapeutic targets for diseases like multiple sclerosis,Alzheimer's disease,and glioma and so on.This review discusses the expression and impact of CXCR3 and its ligands in neurological diseases such as multiple sclerosis,neurologic tumors,neurodegenerative diseases,and neuropathic pain,as well as their associations with CXCR3 ligands.Understanding the mechanisms linking CXCR3 to these diseases could facilitate its potential as an early diagnostic biomarker and a target for drug intervention,and provide the basis of studying the occurrence and developmant of nervous system disease.

Objective:To explore the core medication law of constipation in the Yi Zong Jin Jian using data mining techniques; To provide idea for the clinical treatment of constipation. Methods:The prescriptions related to constipation in the Yi Zong Jin Jian were summarized, and the frequency statistics, the efficiency statistics of the properties and tastes, correlation analysis and complex network analysis were carried out on the data set using the TCM Inheritance Cloud Platform V1.0, and the visualization was carried out. Results:A total of 106 prescriptions for constipation were included, involving 169 kinds of Chinese materia medica, with a total frequency of 894 times. The high-frequency Chinese materia medica included Rhei Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, Scutellariae Radix and Angelicae Sinensis Radix, etc. Chinese materia medica was mainly composed of purging drugs, tonifying drugs and clearing heat drugs. The main tastes were pungent, sweet and bitter, while the main properties were cold and warm, and the main meridians were lung, spleen, stomach and liver meridians. 10 drug combinations such as Rhei Radix et Rhizoma-Scutellariae Radix, Rhei Radix et Rhizoma-Natrii Sulfas were obtained by second-order analysis, 9 drug combinations such as Rhei Radix et Rhizoma-Angelicae Sinensis Radix-Glycyrrhizae Radix et Rhizoma, Scutellariae Radix-Coptidis Rhizoma-Rhei Radix et Rhizoma were obtained by third-order analysis, and 12 categories were obtained by community cluster analysis.Conclusions:In the treatment of constipation in the Yi Zong Jin Jian, it follows the academic thought of "warming, clearing and tonifying". It focuses on the method of tonifying and lowering, and takes warming and tonifying deficiency, clearing heat and defecating as the basic treatment, with cold and warm drugs, based on syndrome differentiation and treatment of zang-fu organs. When treating, it is required to prioritize the disease and treat it according to the syndrome.

Objective To establish a mouse model treated with busulfan and to investigate its effects on the metabo-lism of spermatogonial stem cells(SSCs)of mouse testis.Methods C57BL/6J male mice with age of 8 weeks were injected with 10 mg/kg of busulfan intraperitoneally,then Thy1 positive cells were selected by immunomagnetic beads on day 0,day 5 and day 10 and followed by identification for purity and metabolomic analysis.Results The testis weight ratio decreased and the tissue structure of testis was damaged(P＜0.05).Based on the results of principal component analysis(PCA)and partial least squares discriminant analysis(PLS-DA),there were signifi-cant metabolic differences between the sample groups treated for 0 d,5 d and 10 d.A total of 89 differential metabolites were identified including glutathione(GSH),arginine and unsaturatedfatty acids(UFAs),and their important metabolic pathways involved glycerophospholipid metabolism,arginine and proline metabolism.Conclu-sions Affecting the specific metabolic pathway may result in obvious reproductive toxicity and lead to decrease of testicular weight as well as tissue structure damage in mice.Metabolomic analysis showed that the potential repro-ductive toxicity mechanism of SSCs may be related to the metabolic pathways such as lipid metabolism,arginine and proline metabolism.

Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.

Although the understanding of sepsis has evolved from "sepsis 1.0" to "sepsis 3.0", and the consensus on clinical management of sepsis has been continuously updated, the incidence rate and mortality of sepsis remain high. Therefore, in-depth investigation of the pathogenesis and related influencing factors of sepsis is of great significance for revealing the nature of sepsis and improving the clinical outcome of sepsis patients. This review will focus on the key issues in the basic research of sepsis, and summarize the recent advances and challenges in this field, mainly including genetic polymorphism, microorganisms, high-mobility group box 1 (HMGB1), endothelial dysfunction, immunotherapy, and biomarkers, aiming to provide new insights for the diagnosis and treatment of sepsis.

Objective:To detect the expression levels of laboratory of genetics and physiology 2 (LGP2), retinoic acid inducible gene I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) in children with hand, foot and mouth disease (HFMD), and to explore their possible clinical significance in HFMD.Methods:Fifty children with HFMD, who visited Second Affiliated Hospital of Xi′an Jiao Tong University, Xi ′an Children′s Hospital and Xi ′an Central Hospital from May 2020 to May 2021, were selected as the research subjects, and 20 children with physical examination at the same age during the same period were selected as the control group.Children with HFMD were divided into enterovirus 71 (EV-A71) type and coxsackievirus A6 (CV-A6) type according to the results of pathogen detection, and then divided into mild group and severe group according to the severity of the disease.The relative mRNA expression levels of LGP2, RIG-I and MDA5 in each group, and the correlation among the three proteins were compared and analyzed.Results:Among 50 cases of HFMD, 26 cases were EV-A71 type (16 cases were mild and 10 cases were severe) and 24 cases were CV-A6 type (17 cases were mild and 7 cases were severe). There was no significant difference in age and sex between HFMD group and control group ( P>0.05). The relative expression levels of LGP2 mRNA in EV-A71 and CV-A6 HFMD cases were 2.37(1.78, 3.25)% and 1.88 (1.35, 3.13)%, lower than that in control group [2.97(2.61, 3.55)%]. Only the difference between CV-A6 HFMD children and control group was statistically significant ( Z=-2.310, P=0.021). The relative expression levels of RIG-I mRNA in EV-A71 and CV-A6 HFMD cases were 9.95 (7.79, 14.62)% and 9.78(7.04, 15.83)%, lower than that in control group [18.47(13.00, 21.07)%]. The differences were all statistically significant ( P<0.05). The relative expression levels of MDA5 mRNA in EV-A71 and CV-A6 HFMD cases were 4.41(2.82, 5.99)% and 3.98 (2.18, 7.41)%, lower than that in control group [5.10(3.52, 7.71)%], but the differences were not statistically significant.There were no significant differences in the relative expression levels of the three indicators between the mild and severe groups of children with EV-A71 or CV-A6 HFMD.The expression levels of LGP2, RIG-I and MDA5 mRNA were highly correlated( P<0.001). Conclusion:The relative expression levels of LGP2, RIG-I and MDA5 mRNA in children with HFMD are decreased in different degrees than those in normal children.And there is a correlation among them.

Drastic surges in intracellular reactive oxygen species (ROS) induce cell apoptosis, while most chemotherapy drugs lead to the accumulation of ROS. Here, we constructed an organic compound, arsenical N-‍(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide (AAZ2), which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer (GC). Mechanistically, by targeting pyruvate dehydrogenase kinase 1 (PDK1), AAZ2 caused metabolism alteration and the imbalance of redox homeostasis, followed by the inhibition of phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway and leading to the activation of B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax)/caspase-9 (Cas9)/Cas3 cascades. Importantly, our in vivo data demonstrated that AAZ2 could inhibit the growth of GC xenograft. Overall, our data suggested that AAZ2 could contribute to metabolic abnormalities, leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.
Humans ; Signal Transduction ; Stomach Neoplasms/drug therapy* ; Reactive Oxygen Species/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2 ; Cell Line, Tumor

Objective To investigate the comorbidity of hepatic cystic echinococcosis with HBV/HCV infection, liver cirrhosis, and hepatocellular carcinoma, and to lay a foundation for further research on the influence of hepatic cystic echinococcosis on HBV/HCV infection, liver cirrhosis, and hepatocellular carcinoma. Methods A retrospective analysis was performed for the data of 401 patients with hepatic cystic echinococcosis who were admitted to The First Affiliated Hospital of Shihezi University from 2003 to 2019, and the state of comorbidity of hepatic cystic echinococcosis with HBV/HCV infection, liver cirrhosis, and hepatocellular carcinoma was clarified. The patients with hepatic cystic echinococcosis and chronic HBV/HCV infection were selected as comorbidity group, and the patients with HBV/HCV infection alone were matched as control group. The chi-square test and the Fisher's exact test were used to analyze the state of viral infection and the disease composition of liver cirrhosis and hepatocellular carcinoma. Results Of all 401 patients, 38(9.5%) were included in the comorbidity group and 2(0.5%) had liver cirrhosis after HBV/HCV infection, while no patient had hepatocellular carcinoma after HBV/HCV infection. Among the patients with chronic hepatitis B virus infection in the comorbidity group, non-active HBsAg carriers accounted for 81%, HBeAg-positive chronic hepatitis B patients accounted for 9.5%, and HBeAg-negative chronic hepatitis B patients accounted for 9.5%; among the patients with hepatitis B virus infection in the control group, non-active HBsAg carriers accounted for 43%, HBeAg-positive chronic hepatitis B patients accounted for 33%, and HBeAg-negative chronic hepatitis B patients accounted for 19%, with a significant difference between the two groups ( P =0.033). There was a significant difference in the HBV RNA clearance rate of the patients with HCV infection between the comorbidity group and the control group ( χ 2 =4.447, P =0.035). In the comorbidity group, the patients with liver cirrhosis accounted for 5.2% and there were no patients with hepatocellular carcinoma, while in the control group, the patients with liver cirrhosis accounted for 18.4% and those with hepatocellular carcinoma accounted for 5.2%; the comorbidity group had significantly lower proportions than the control group ( P =0.048). Conclusion The proportion of liver cirrhosis patients with hepatic cystic echinococcosis and HBV/HCV infection is lower than that of liver cirrhosis patients with viral hepatitis alone, and there are no cases of hepatocellular carcinoma after HBV/HCV infection. Further multicenter studies are needed to investigate the influence of hepatic cystic echinococcosis on chronic HBV/HCV infection, liver cirrhosis, and hepatocellular carcinoma.

Objective     To summarize the progress and trend on clinical drug trials of esophageal squamous cell carcinoma in China. Methods     Based on the clinical drug trial registration and information disclosure platform and the drug data query system of the National Medical Products Administration, the characteristics of clinical trials, investigational drugs and listed drugs of esophageal squamous cell carcinoma in China from 2012 to 2021 were analyzed. Results     From 2012 to 2021, a total of 49 clinical drug trials of esophageal squamous cell carcinoma were registered in China, accounting for 1.6% of all clinical trials of anticancer drugs. Among them, there were 39 (79.6%) trials initiated by domestic pharmaceutical enterprises, 6 (12.2%) for adjuvant and neoadjuvant treatment, and 9 (18.4%) for local treatment. There were differences in the treatment line distribution between global and domestic enterprise-initiated trials (P=0.032). The above trials covered 29 investigational drugs, including 23 (79.3%) targeted drugs, most of which targeted programmed death-1, programmed death-ligand 1 and epidermal growth factor receptor. From 2012 to 2021, there were 2 drugs for esophageal squamous cell carcinoma listed in China, both of which were approved for the first-line and second-line treatment. Conclusion     Great achievements have been made in the clinical development of esophageal squamous cell carcinoma drugs in China. It is suggested that domestic enterprises increase the investment of esophageal squamous cell carcinoma, pay attention to adjuvant and local treatment, explore novel targets and drug categories, and focus on the details of pivotal trials.

Objective:To understand the current situation and influencing factors of psychological stress reaction in patients with multi-drug resistance tuberculosis (MDR-TB) and to analyze the moderating effect of social support level between medical coping style and psychological stress reaction.Methods:This study was a cross-sectional study. Using the convenient sampling method, a total of 273 patients with MDR-TB who were hospitalized in the Tuberculosis Department of West China Hospital, Sichuan University from July 2019 to December 2020 were selected as the research objects. The Impact of Event Scale-Revised (IES-R) , Social Support Rating Scale (SSRS) and Medical Coping Modes Questionnaire (MCMQ) were used to investigate them. The χ 2 test and t test were used for univariate analysis, binomial logistic regression analysis was used for multivariate analysis and PROCESS V 3.3 software was used for moderating effect analysis. Results:A total of 37.36% (102/273) of MDR-TB patients had severe psychological stress reaction. Logistic regression analysis showed that age ( OR=1.039, 95% CI: 1.003-1.076) , marital status ( OR=0.136, 95% CI: 0.024-0.773) , occupation ( OR=0.057, 95% CI: 0.011-0.312) , daily alcohol consumption ( OR=28.968, 95% CI: 2.387-351.609) , social support level ( OR=0.927, 95% CI: 0.866-0.993) and patients' yielding psychology in the face of disease ( OR=2.216, 95% CI: 1.761-2.788) were independent factors affecting the psychological stress response of MDR-TB patients. The level of social support had significant moderating effects on avoidance (β=-0.132, P=0.002) , confrontation (β=-0.068, P=0.038) and psychological stress in MDR-TB patients. The more the patients with high social support level adopted the coping style of facing or avoiding, the lower the score of the event impact scale, that was, the weaker the psychological stress reaction. Conclusions:Medical staff should pay attention to the psychological stress reaction of MDR-TB patients and conduct targeted psychological counseling to enhance social support level of patients and improve treatment compliance, thereby reducing the recurrence rate of tuberculosis.