ObjectiveTo explore the potential mechanism of Dingchuan Granule （定喘颗粒， DG） in the treatment of respiratory syncytial virus （RSV） pneumonia. MethodsA total of 60 male Sprague Dawley （SD） rats were randomly divided into control group， model group， ribavirin group， DG low-dose group， DG middle-dose group， and DG high-dose group， with 10 rats in each group. Except for the control group， rats were administrated with RSV via intranasal drip. After model establishment， the DG low-， middle-， and high-dose groups were administrated via oral gavage with DG at 3.47， 6.93， and 13.86 g/（kg·d） respectively， while the ribavirin group was administrated via oral gavage with ribavirin at 15.75 mg/（kg·d）. The drug was given once daily for one week. The rats in the control group and the model group were not given any drug， only subjected to the grasping action. Twenty-four hours after the last administration， the pathological changes of lung tissues were observed and scored using HE staining. The levels of serum inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）， were detected by colorimetry. The protein levels of nuclear factor （erythroid derived 2）-like 2 （Nrf2）， Kelch-like ECH-associated protein 1 （Keap1）， heme oxygenase 1 （HO-1）， and NAD（P）H quinone dehydrogenase 1 （NQO1） in lung tissues were measured by Western Blot. The RSV load as well as the gene expression levels of Nrf2， Keap1， HO-1， and NQO1 in lung tissues were determined by qRT-PCR. The level of reactive oxygen species （ROS） in rat lung tissues was detected using chemiluminescence. The levels of glutathione （GSH） and malondialdehyde （MDA） in rat lung tissues were measured by a microassay. ResultsCompared with the control group， other groups had significant increases in pathological score of lung tissue， RSV load， levels of ROS， MDA， serum TNF-α， IL-1β， and IL-6； decrease in GSH level， increases in expression level of Keap1 protein and its mRNA in lung tissue， and significant decrease in levels of Nrf2， HO-1， expression level of NQO1 protein and its mRNA （P＜0.05）. Compared with the model group， all the above-mentioned indicators in the DG low-， middle-， and high-dose groups and the ribavirin group were improved to varying degree （P＜0.05）. The levels of serum TNF-α， IL-1β， and IL-6 in rats of DG dose groups showed a dose-dependent pattern， the DG high-dose group exhibiting the best effect （P＜0.05）. The DG high-dose group was superior to the DG low- and middle-dose groups in reducing the levels of ROS and MDA， and increasing the level of GSH in lung tissues （P＜0.05）. The DG high-dose group and the ribavirin group had better effect than the DG middle-dose group in reducing the RSV load （P＜0.05）. The DG high-dose group was superior to the ribavirin group in improving the protein levels of Nrf2， Keap1， HO-1， and NQO1 （P＜0.05）. ConclusionDG could inhibit oxidative stress by regulating the Nrf2/Keap1/HO-1/NQO1 signaling pathway to improve pulmonary inflammation and treat RSV pneumonia， with the DG high-dose group showing the best effect.

ObjectiveTo investigate the mechanism of the modified of Bazhentang combined with Guishentang in improving pregnancy outcomes in mouse models of embryo implantation dysfunction by regulating T helper 1/T helper 2 （Th1/Th2） immune balance. MethodsEighty ICR female mice were randomly divided into four groups （n=20 per group） on gestational day 1 （GD1）： control， model， western medicine， and traditional Chinese medicine （TCM） groups. Except for the control group， all mice received mifepristone solution （0.2 mg/mouse） via oral gavage on GD4 to induce embryo implantation dysfunction. The TCM group received a water decoction of the modified of Bazhentang combined with Guishentang （20.8 g·kg^-1）， with the western medicine group administered dydrogesterone （3.9 mg·kg^-1）， and the control/model groups given equal volumes of saline. All treatments were administered once daily from GD1 until one day before sample collection. Outcomes included implantation site counts （macroscopic observation）， pregnancy rates， body weight， endometrial histopathology （hematoxylin-eosin staining）， uterine expression of T-box expressed in T cells （T-bet）， GATA-binding protein 3 （GATA3）， interferon gamma （IFN-γ）， and interleukin-4 （IL-4） at protein （Western blot） and mRNA （real-time polymerase chain reaction， Real-time PCR） levels， serum IFN-γ and IL-4 levels （enzyme-linked immunosorbent assay， ELISA）， and Th1/Th2 immune balance evaluated by calculating T-bet/GATA3 and IFN-γ/IL-4 ratios. ResultsCompared to the control group， the model group showed no significant change in pregnancy rate but exhibited a marked reduction in average implantation sites and body weight （P<0.01）. Histopathological analysis revealed endometrial abnormalities， including decreased glandular density， stromal compaction， and absence of nucleolar vacuoles. At the molecular level， uterine tissue in the model group demonstrated significantly upregulated expression of T-bet and IFN-γ （P<0.05， P<0.01）， alongside markedly downregulated GATA3 and IL-4 expression （P<0.05， P<0.01）. Serum analysis confirmed markedly elevated IFN-γ （P<0.01） and reduced IL-4 levels （P<0.01）， resulting in significantly increased T-bet/GATA3 and IFN-γ/IL-4 ratios （P<0.01）. Compared to the model group， pregnancy rates in all treatment groups showed no significant change. Implantation sites and body weight increased substantially （P<0.01）， with restored endometrial morphology characterized by enhanced glandular density， stromal edema， and reappearance of nucleolar vacuoles. Significant downregulation of T-bet and IFN-γ （P<0.01） and upregulation of GATA3 and IL-4 （P<0.05， P<0.01） in uterine tissue were observed. Serum IFN-γ levels were significantly reduced （P<0.05， P<0.01）， while IL-4 levels were significantly elevated （P<0.05）. The Th1/Th2 ratios were significantly decreased （P<0.01）. ConclusionThe modified of Bazhentang combined with Guishentang significantly enhances the number of embryo implantation sites in mice with embryo implantation dysfunction， potentially through modulating T-bet/GATA3 expression， restoring Th1/Th2 immune balance， and improving endometrial receptivity.

Ketamine， a non-competitive N-methyl-D-aspartate （NMDA） receptor antagonist， has gained increasing attention for its rapid antidepressant effects in treatment-resistant depression （TRD） and suicidal ideation. Its mechanisms include NMDA receptor blockade， AMPA receptor activation， and upregulation of BDNF/mTOR signaling. Its enantiomers， esketamine and R-ketamine， as well as its metabolites， exhibit differences in efficacy and mechanisms. Intranasal esketamine has been approved in the Europe， United States， and China for TRD， demonstrating rapid efficacy in alleviating depressive symptoms and acute suicidal ideation. In contrast， R-ketamine demonstrates potential for longer-lasting effects and a improved safety profile. This review summarizes recent advances in the pharmacology， pharmacokinetics， and clinical applications of ketamine and its enantiomers in depressive disorders， bipolar disorder， substance use disorders， post-traumatic stress disorder and obsessive-compulsive disorder. Despite ketamine's multifaceted therapeutic potential， safety concerns such as dissociation， cognitive impairment， and abuse liability warrant continued attention.［Funded by Key Project of Natural Science Research for Universities of Anhui Provincial Education Department （number， 2023AH050647）； Anhui Provincial Department of Education Outstanding Young Talent Support Program Project 2022 （number， gxyqZD2022022）］

Objective:To compare the efficacy of pars plana vitrectomy (PPV) combined with human amniotic membrane (hAM) plugging technique or internal limiting membrane (ILM) flap insertion technique for high myopia macular hole retinal detachment (MHRD).Methods:A non-randomized controlled clinical study was performed.Sixteen eyes of 15 patients with high myopia MHRD treated in the Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine from July 2020 to August 2021 were included.All patients underwent PPV and were divided into hAM plug group (7 eyes of 7 patients) and the ILM insertion group (9 eyes of 8 patients) based on the different plugging materials.The best corrected visual acuity (BCVA) and intraocular pressure were measured before surgery and at 1 week, 1, 3, and 6 months postoperative, respectively.Slit-lamp microscopy combined with lenses, scanning laser ophthalmoscope and optical coherence tomography (OCT) were used to examine the fundus, the macular hole closure and retinal reposition.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (No.SH9H-2021-T322-2). Written informed consent was obtained from each subject.Results:The retinal reattachment was achieved in 6 eyes in the hAM plug group and all 9 eyes in the ILM insertion group after initial surgery.The macular hole closure was observed in 5 eyes in the hAM plug group and 8 eyes in the ILM insertion group after initial surgery, and there was no statistical difference in the macular hole closure rate between the two groups ( P>0.05). There were significant differences in the overall comparison of BCVA between the two groups over time ( Ftime=4.420, P<0.05). Postoperative BCVA at different time points was better than preoperative BCVA in each group, but the differences were not significant (all at P>0.05). There was no significant difference in the overall comparison of BCVA between the two groups ( Fgroup=0.183, P>0.05). Two eyes in the hAM plug group and 4 eyes in the ILM insertion group developed transient ocular hypertension, which returned to normal after 1 week of treatment. Conclusions:Both PPV combined with hAM plugging technique and ILM insertion technique are safe and effective for the treatment of MHRD in high myopia.The hAM plugging technique can not only achieve anatomical reduction but also functional recovery of the retina even in complicated fundus conditions.

AIM: To explore a more convenient and accurate method for evaluating the anterior chamber angle width based on the Van Herick method.METHODS:A total of 58 patients(69 eyes)with age-related cataract who visited our hospital between January and December 2021 were included. They were divided into the chamber angle width ≥1/2 corneal thickness(CT)group(44 eyes of 37 cases)and <1/2CT group(25 eyes of 21 cases)according to the Van Herick method. The central anterior chamber depths and the peripheral anterior chamber angle degrees were measured by ultrasound biomicroscopy.RESULTS: There were statistically significant differences in central anterior chamber depth between the two groups(2.64±0.27 mm vs. 2.23±0.29 mm, P<0.01), and the differences of chamber angle degrees of quadrants of superior, temporal, inferior and nasal compared between two groups were all statistically significant(P<0.01). The difference of chamber angle degrees of quadrants of superior and inferior in chamber angle width ≥1/2CT group was not statistically significant(P>0.05), while the differences of chamber angle degrees of other quadrants were all statistically significant(P<0.05). The differences of chamber angle degrees of quadrants of superior and nasal, temporal and the chamber angle degrees of quadrants of inferior and temporal were all statistically significant in chamber angle width <1/2CT group(P<0.05).CONCLUSION: In the overall evaluation of the anterior chamber angle, it would be more simple, fast and accurate when evaluating the temporal chamber angle width and inferior quadrant of chamber angle width by using the Van Herick method under silt lamp.

Objective:This study aimed to explore the status of radiological Kashin-Beck disease (KBD) among school-aged children in Chamdo City, Tibet, through a 3-year monitoring survey, providing epidemiological evidence for prevention and control strategies.Methods:The target areas for this study were Luolong, Bianba, and Basu counties in Chamdo City, Tibet Autonomous Region, identified as having the most severe historical cases of KBD. Children aged 7-12 years attending school were enrolled as study subjects. Anteroposterior X-ray films of the right-hand were taken, and radiological diagnoses were made based on the "Diagnosis of Kashin-Beck Disease" criteria (WS/T 207-2010). Two experienced researchers independently reviewed the X-rays, and intra- and inter-group consistency were assessed using weighted Kappa values and percentage agreement. Cross-sectional surveys were conducted in 2017 and 2020 to describe the X-ray detection rates of KBD, and logistic regression analysis was employed to construct a predictive model of risk factors for radiological KBD cases.Results:In 2017, a total of 5,711 children aged 7-12 years in Chamdo City, Tibet, participated in the baseline cross-sectional survey (average age 9.2 years, 48.0% female), with 28 cases of radiological KBD. The age- and gender-standardized prevalence rate was 0.527%. In 2020, 6,771 participants (average age 9.3 years, 49.5% female) underwent a second cross-sectional survey, with 9 cases of radiological KBD and a standardized prevalence rate of 0.134%. Logistic regression analysis indicated that older age [ OR=2.439, 95% CI(1.299, 4.580), P=0.006] and female gender [ OR=8.157, 95% CI(1.016, 65.528), P=0.048] were independent risk factors for radiological KBD cases. Conversely, higher residential altitude, under the premise of Tibet's high altitude, was a protective factor [ OR=0.995, 95% CI(0.990, 0.999), P=0.032). Conclusion:The radiographically positive detection rate of KBD among school-aged children in Chamdo City, Tibet Autonomous Region, is at an extremely low level and showing a declining trend, reaching the historical standard in 2020. Considering the absence of positive signs in affected children, it suggests that local KBD has been effectively eliminated.

Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.

Objective To investigate the associations between thyroid hormone sensitivity indices in euthyroid patients with hypertension and the risk of ischemic stroke,as well as gender difference in this association.Methods We selected 760 hypertensive patients admitted to the Geriatric Neurology Department and outpatient clinic in The Second Affiliated Hospital of Xi'an Jiaotong University between April 2021 and May 2022.We collected their basic characteristics,blood biochemical parameters,thyroid indices,and brain magnetic resonance imaging information.All the patients were divided into two groups based on the clinical manifestations and brain magnetic resonance imaging:hypertension combined with ischemic stroke(n=526)and control(n=234)groups.Independent sample t-tests or non-parametric tests were used to compare the differences in thyroid hormone sensitivity indicators between the two groups.Spearman correlation analysis was used to analyze the correlation between serum thyroid indices and ischemic stroke.Multivariate conditional Logistic regression analysis was made to estimate odds ratios(ORs)and 95％confidence intervals(CIs)for thyroid indices and ischemic stroke.Results There were statistically significant differences between the two groups in terms of age,gender,TC,LDL-c,HDL-c,systolic blood pressure,FT3/FT4,TFQI,and PTFQI(all P＜0.05).However,there was no statistically significant difference between the two groups in weight,smoking,drinking,history of diabetes,TG,FBG,diastolic blood pressure,TSHI,or TT4RI(all P＞0.05).The results of Spearman correlation analysis showed a negative correlation between FT3/FT4 and ischemic stroke(P＜0.05),but a positive correlation of TFQI and PTFQI with ischemic stroke(P＜0.05)in euthyroid patients with hypertension.Logistic regression analysis showed that FT3/FT4 was significantly associated with ischemic stroke in euthyroid patients with hypertension(P=0.001),with OR(95％CI)of 0.001(0.000,0.058).After stratifying by gender,Logistic regression analysis found that FT3/FT4,TFQI,and PTFQI were associated with an increased risk of ischemic stroke in female patients,with OR(95％CI)of 0.000(0.000,0.001),3.132(1.415,6.930),and 3.010(1.406,6.445),respectively.Conclusion Lower serum FT3/FT4 ratio is associated with an increased risk of ischemic stroke in euthyroid patients with hypertension,and the significant association of TFQI and PTFQI with the risk of ischemic stroke is found in females.

Objective:To construct a recombinant bioluminescent bacteriophage (HT7) targeting Escherichia coli, and evaluate its ability to identify Escherichia coli. Methods:Initially, pCRISPR-sg (1-10) and PFN-1000 plasmid strains were constructed by genetic engineering, and the most efficient small guild RNA (sgRNA) were screened by bilayer plate. By the gene editing technique, which comprised homologous recombination and clustered regularly interspaced short palin dromic repeats (CRISPR)-Cas system, the Nanoluc luciferase gene was integrated into the downstream non-coding region of 10A gene of T7 phage, to constructe the bioluminescent phage HT7 successfully. The difference of biological characteristics between HT7 phage and T7 phage was evaluated by plaque assay and liquid amplification assay. In addition, 51 strains of Escherichia coli, 20 strains of Klebsiella pneumoniae, 14 strains of Staphylococcus aureus, 6 strains of Enterococcus faecium, 5 strains of Enterococcus faecalis, 3 strains of Acinetobacter baumannii and 1 strain of Pseudomonas aeruginosa were collected and isolated to evaluate the limit of detection and specificity of HT7 phage. Results:Among the 10 CRISPR-targeted cleavage systems constructed, sgRNA8 exhibited the highest cleavage efficiency, with a cleavage rate of 0.18. After three rounds of recombination screening using the pCas9/pCRISPR/PFN-1000 triple-plasmid system, PCR validation yielded recombinant phage bands at 2 798 bp, indicating the successful construction of the HT7 phage. The recombinant phage showed significant differences in biological characteristics in terms of lysis efficiency ( P<0.001), one-step growth curve ( P=0.001), and infection multiplicity ( P=0.031). Both lysis burst time and log growth node were extended by 10 min, with the optimal infection multiplicity being 0.1. Clinical sample testing identified lysis of 6 strains of Escherichia coli within 4.5 h, while other strains remained unaffected, with detection of pathogenic bacteria below 10 CFU/ml. Conclusions:The developed pCas9/pCRISPR/PFN-1000 triple-plasmid editing system efficiently edits the bacteriophage genome. The constructed HT7 fluorescent bacteriophage enables the detection of Escherichia coli below 10 CFU/ml within 4.5 hours, demonstrating low detection limits and high detection specificity.

Objective To discuss the medication law of Professor Gu Shizhe in the treatment of insomnia based on various data mining techniques.Methods Clinical information of patients of Professor Gu was collected from the hospital management information system of outpatient clinic of Beijing University of Chinese Medicine(BUCM)and BUCM Famous Elderly TCM Inheritance Research Integrated Platform from January 2018 to October 2022.Professor Gu's books,such as Zhi Zhen Zhi Yao,and Gu Jisheng,Gu Shizhe Yi An Yi Hua Jing Cui,and the medical records from CNKI were screened.WPS Office 5.2.1 was used to build a database of medicine data for Professor Gu's TCM prescriptions,and R 4.2.1 was used for descriptive analysis and Apriori association rule analysis.SPSS Statistics 26.0 was used for clustering analysis,combined with theoretical analysis,to extract Professor Gu's medication law and characteristics in the treatment of insomnia.Results A total of 307 prescriptions were included,involving 250 kinds of Chinese materia medica,among which 30 were high-frequency drugs.The top 5 most frequently used were Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle,Fossilizid,Poria,Bupleuri Radix,and Ziziphi Spinosae Semen.The meridians were mainly liver and lung meridian,and the properties were mainly warm and cold,and the tastes were mainly sweet and bitter.Five core drug groups were obtained by clustering analysis,including Xiaochaihu Decoction,Erchen Decoction,Huanglian Wendan Decoction,Suanzaoren Decoction,Xiaoyao Powder and other prescriptions.Conclusion The characteristics of Professor Gu's treatment of insomnia are to reconcile Shaoyang,clear the heart and soothe the mind;pay attention to yin and yang,regulate the liver;pay attention to the liver,gallbladder,spleen and stomach;the main idea of syndrome differentiation is to reconcile Shaoyang,run the Shaoyang cardinal,and at the same time regulate qi and benefit qi and nourishes yin.