ObjectiveTo investigate the possible mechanism of Buzhong Yulin Decoction （补中愈淋汤） in the prevention and treatment of recurrent urinary tract infection. MethodsThe mouse models of recurrent urinary tract infection were established by uropathogenic Escherichia coli （UPEC） strain UTI89 by bladder perfusion， and the successful mouse models were randomly divided into a model group， an antibiotic group， and a low- and high-dose Buzhong Yulin Decoction group， with six mice in each group. In addition， 5 C57BL/6 mice without modelling were taken as blank group. The low- and high-dose Buzhong Yulin Decoction groups received 0.1 ml/10 g of decoction by gavage， with concentrations of 1.3 g/ml and 5.2 g/ml， respectively； the antibiotic group received 0.1 ml/10 g of levofloxacin hydrochloride solution with 5 mg/ml by gavage； the blank and model groups received 0.1 ml/10 g of distilled water by gavage. Each group was gavaged once a day for 7 consecutive days. The total number of urine marks， the number of central urine marks， and the total urine volume of the urine marks were observed by the urine marking test； HE staining was used to observe the histopathological changes in the bladder of mice； serum levels of the inflammatory factors interleukin 1β （IL-1β）， interleukin 6 （IL-6） and tumour necrosis factor α （TNF-α） were detected by ELISA； the morphology of the epithelial cells of bladder was observed by scanning electron microscopy； immunofluorescence assay to detect bladder tissue anti-UroPlakin 3A protein level and UPEC bacterial load； the spread plate method to detect urinary bacterial load and bacterial load of bladder epithelial cells； RT-PCR method to detect Ras-related protein Rab-11A （RAB11A） and Ras-related protein Rab-27B （RAB27B） mRNA level in bladder tissue； immunoblotting to detect microtubule-associated protein 1 light chain3 （LC3） and P62 protein levels in bladder tissue. ResultsCompared with the blank group， the bladder epithelial cell layers were lost and showed abnormal morphology in mice of the model group； bladder tissue UroPlakin 3A protein and RAB11A and RAB27B mRNA levels reduced， the total number of urine marks， the number of central urine marks， bladder tissue UPEC bacterial load， urinary bacterial load， bacterial load in bladder epithelial cells， serum IL-1β， IL-6， and TNF-α levels， and LC3 and P62 protein levels in bladder tissue all elevated （P＜0.05 or P＜0.01）. Compared with the model group， the bladder epithelial cell layers were intact and the morphology of epithelial cells were regular in the low- and high-dose Buzhong Yulin Decoction groups； the average surface area of bladder epithelial cells reduced， the levels of UroPlakin 3A protein and RAB11A and RAB27B mRNA in bladder tissues elevated， and total number of urine marks， the number of central urine marks， bladder tissue UPEC bacterial load， urinary bacterial load， bacterial load in bladder epithelial cells， serum IL-1β， IL-6， and TNF-α levels， and P62 protein levels in bladder tissue all reduced （P＜0.05 or P＜0.01）， but LC3 protein levels showed no statistically significant （P＞0.05）. In the antibiotic group， the bladder epithelial cells were partially missing and the morphology of epithelial cells was abnormal. Compared with the antibiotic group， the average surface area of the bladder epithelial cells in the mice increased in the low- and high-dose Buzhong Yulin Decoction groups， the bacterial load of the bladder epithelial cells decreased， and the P62 protein level of the bladder tissue decreased （P＜0.05）. When comparing between the low- and high-dose Buzhong Yulin Decoction groups， the differences in each index were not statistically significant （P＞0.05）. ConclusionBuzhong Yulin Decoction may prevent and treat recurrent urinary tract infection by repairing the bladder mucosal barrier， increasing RAB11A and RAB27B level and enhancing autophagy in bladder tissues， thereby facilitating bacterial clearance from bladder epithelial cells and reducing the bacterial load of bladder epithelial cells.

Objective:To analyze brain topological property data through machine learning methods and explore changes in brain network topological properties in patients with schizophrenia.Methods:From January 2022 to August 2023, functional magnetic resonance imaging data of 60 patients with schizophrenia and 56 healthy controls were collected , and the data were preprocessed to construct brain functional networks and extract global and nodal topological properties. All subjects were divided into a training group and a testing group.The data of training group were fitted based on support vector machine, and the predictive performance was evaluated through cross-validation.The model was optimized by recursive feature elimination algorithm, then the indicators that contributed the most to predictive performance were extrated.The classification performance of the testing group was calculated based on the trained model with optimal predictive performance.SPSS 20.0 software was used for data analysis, the independent t-test and χ2 test were used for comparing the differences between the two groups. Results:The support vector machine achieved an accuracy of 75.00% in predicting the test group of schizophrenia patients based on all indicators. After removing redundant features and combining with the recursive feature elimination algorithm, the accuracy of the SVM model in predicting the test group increased to 90.00%. The nodal global efficiency(Ne)of the left superior temporal gyrus, right dorsal agranular insula, bilateral dorsal granular insula, bilateral caudal cingulate gyrus, and left lateral orbitofrontal cortex in the model contributed the most to classification.Compared to the control group, patients with schizophrenia had abnormal Ne values in these brain regions.Conclusion:There are multiple brain regions with abnormal Ne values in patients with schizophrenia, indicating that the abnormalities in information integration and transmission functions may be related to the imbalance in the dynamic equilibrium of the patients' brain networks.

Objective:To investigate the application effect of the blended teaching model of "intelligent teaching" and "wisdom learning" in the practice teaching of integrated traditional Chinese and Western medicine in internal medicine.Methods:According to the principle of randomization, 54 interns in Class 1 of integrated traditional Chinese and Western medicine in the grade of 2019 were selected as control group and received traditional teaching, and 56 interns in Class 2 were selected as observation group and received blended teaching with "intelligent teaching" and "wisdom learning". After 6 months of internship, the two groups were compared in terms of the scores of theoretical assessment (basic theoretical knowledge and professional theoretical knowledge), clinical practice ability [Leicester Assessment Package (LAP)], and degree of satisfaction with teaching. SPSS 17.0 was used to perform the t-test and the chi-square test. Results:At the end of internship, compared with the control group, the observation group had significantly higher score of basic theoretical knowledge (41.53±3.42 vs. 38.71±3.38, P<0.05), score of professional theoretical knowledge (39.49±3.14 vs. 37.85±3.07, P<0.05), LAP score (84.32±6.65 vs. 78.46±6.17, P<0.05), and degree of satisfaction with teaching ( P<0.05). Conclusion:For interns majoring in integrated traditional Chinese and Western medicine, the blended teaching model of "intelligent teaching" and "wisdom learning" can strengthen their mastery of theoretical knowledge, enhance their clinical practice ability, and improve their degree of satisfaction with teaching.

ObjectiveTo investigate the effect of hypoxia-inducible factor-1α (HIF-1α) on the stemness and epirubicin sensitivity of hepatoma cells. MethodsHepatoma cells were selected for experiment. HepG2 hepatoma cells transfected with HIF-1α overexpression plasmid were selected as experimental group, and those transfected with pcDNA3.1 empty plasmid were selected as control group; HepG2 cells alone were selected as HepG2 group. Quantitative real-time PCR was used to measure the mRNA expression of HIF-1α; Western blot was used to measure the protein expression of HIF-1α; flow cytometry was used to measure the expression of CD133 on the surface of hepatoma cells. The three groups of cells were treated with epirubicin at different concentrations (0, 6.25, 12.5, 25, and 50 μmol/L) for 24 hours; MTT assay was used to measure cell viability, and flow cytometry was used to measure apoptosis after treatment with epirubicin (50 μmol/L). A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the t-test was used for further comparison between two groups. ResultsCompared with the HepG2 group and the control group, the experimental group had a significant increase in the mRNA expression of HIF-1α (both P＜0.001), and Western blot showed high expression of HIF-1α in the experimental group. The percentage of CD133 cells was 0.040%±0.003% in the HepG2 group, 0.030%±0.010% in the control group, and 20.110%±0.600% in the experimental group, and the experimental group had a significantly higher positive rate of CD133+ than the HepG2 group and the control group (both P＜0.001). At an epirubicin concentration of 25 and 50 μmol/L, the HepG2 group and the control group had significantly inhibited cell viability and a significantly lower cell viability than the experimental group (both P＜005). After the treatment with 50 μmol/L epirubicin for 48 hours, the experimental group had a significantly lower cell apoptosis rate than the HepG2 group (67.9%±2.5% vs 93.6%±1.5%, P＜0.001) and the control group (67.9%±2.5% vs 93.0%±1.2%, P＜0001). ConclusionHepG2 cells are successfully transfected with HIF-1α overexpression plasmid, and HIF-1α can increase the percentage of liver cancer stem cells and improve their resistance to epirubicin.

Objective:To observe the analgesic effect of local anesthesia combined with nerve block anesthesia on golden microneedles for improving facial aging.Methods:Between December 2018 and December 2019 in Burn and Plastic Surgery of Nanchong Central Hospital, sixty female patients (between 30 and 58 years old, with an average of 45.2 years old) with natural facial skin aging were randomly divided into two groups: Group A: surface anesthesia group (30 cases); Group B: local anesthesia combined with nerve block anesthesia (30 cases). Intraoperative and postoperative pain scores, length of operation, and incidence of adverse reactions were compared between groups A and B.Results:Pain score during surgery was (6.90±0.96) points in Group A, (3.63±0.72) points in Group B. The difference between the two groups was statistically significant ( t=14.93, P<0.05); Pain score at 30 minutes after operation was (2.03±0.62) in Group A, (0.77±0.73) in Group B, the difference between the two groups was statistically significant ( t=7.28, P<0.05). There was no statistically significant difference between the two groups in the pain score at 24 hours after operation ( P>0.05); The operation process in group B was simplified, and the treatment time was significantly shortened. The difference between the two groups was statistically significant ( t=17.93, P<0.05). Conclusions:The method of local anesthesia combined with nerve block anesthesia is used in the treatment of gold microneedles to improve the analgesic effect in facial aging, which significantly shortens the treatment time and has fewer adverse reactions. This method is worth popularizing.

Objective:To explore the abnormalities of efficiency in resting state functional brain network in patients with paranoid schizophrenia and the correlations between efficiencies and clinical symptoms.Methods:A total of 73 patients with schizophrenia (SZ group) met with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-Ⅳ) criteria for schizophrenia and 70 healthy controls (HC group) were included .All subjects were checked by using functional magnetic resonance imaging (fMRI), and positive and negative syndrome scale(PANSS) were used to assess the symptoms.Abnormalities of global and local efficiency of brain regions in brain functional network were analyzed by graph theory.Pearson correlation was used to analyze the correlation between the abnormal global efficiency and local efficiency of brain regions of SZ group and PANSS.SPSS 20.0 software was used for dependent-sample t-test, ANOVA test and Pearson correlation analysis. Results:Compared with the HC group, SZ group showed increased global efficiency in bilateral thalamus(left: 0.26±0.06, 0.28±0.04, t=2.03, P=0.044.right: 0.26±0.06, 0.28±0.05, t=2.08, P=0.040), right orbital part of middle frontal gyrus(0.21±0.04, 0.23±0.05, t=2.25, P=0.026), cerebellar lobule Ⅸ(0.19±0.06, 0.21±0.05, t=2.56, P=0.011) and vermis Ⅲ(0.15±0.08, 0.19±0.07, t=3.27, P=0.001), while decreased global efficiency in bilateral parahippocampal gyrus(left: 0.25±0.05, 0.22±0.05, t=-3.34, P=0.001.right: 0.27±0.04, 0.23±0.05, t=-4.96, P=0.000), superior occipital gyrus(left: 0.27±0.03, 0.26±0.03, t=-2.70, P=0.008.right: 0.27±0.02, 0.26±0.03, t=-2.73, P=0.007), superior parietal gyrus(left: 0.27±0.03, 0.26±0.05, t=-2.63, P=0.010.right: 0.27±0.03, 0.25±0.05, t=-2.76, P=0.007), paracentral lobule(left: 0.28±0.03, 0.26±0.07, t=-2.47, P=0.015.right: 0.28±0.04, 0.25±0.07, t=-3.06, P=0.003), left precental gyrus(0.28±0.04, 0.27±0.04, t=-1.98, P=0.049), left cuneus(0.26±0.04, 0.25±0.04, t=-2.08, P=0.039), left lingual gyrus(0.29±0.03, 0.28±0.03, t=-2.28, P=0.024), left middle occipital gyrus(0.29±0.03, 0.28±0.03; t=-2.74, P=0.007), left middle temporal gyrus(0.28±0.03, 0.26±0.03, t=-2.73, P=0.007), temporal pole in left middle temporal gyrus(0.20±0.06, 0.18±0.06, t=-2.59, P=0.011) and right hippocampus(0.27±0.04, 0.26±0.06, t=-2.05, P=0.042).Compared with the HC group, SZ group showed increased local efficiency in bilateral caudate nucleus(left: 0.33±0.06, 0.35±0.05, t=2.54, P=0.012.right: 0.33±0.07, 0.35±0.04, t=2.77, P=0.007) and left superior occipital gyrus(0.39±0.03, 0.40±0.02, t=2.17, P=0.031), while decreased local efficiency in bilateral parahippocampal gyrus(left: 0.35±0.04, 0.32±0.07, t=-3.16, P=0.002.right: 0.34±0.04, 0.32±0.07, t=-2.91, P=0.004), left supplementary motor area(0.36±0.02, 0.35±0.05, t=-2.01, P=0.047), left inferior parietal but supramarginal and angular gyrus(0.35±0.03, 0.34±0.05, t=-2.65, P=0.009), left cerebellar crus Ⅱ(0.37±0.03, 0.36±0.04, t=-2.01, P=0.046), lobule ⅦB(0.37±0.03, 0.35±0.07, t=-1.98, P=0.049), right posterior cingulate gyrus(0.36±0.04, 0.34±0.07, t=-2.07, P=0.041), right superior parietal gyrus(0.37±0.03, 0.36±0.05, t=-2.19, P=0.031), right precuneus(0.36±0.02, 0.35±0.04, t=-2.36, P=0.020), right paracentral lobule(0.37±0.02, 0.36±0.06, t=-2.07, P=0.041) and right temporal pole in middle temporal gyrus(0.33±0.08, 0.30±0.09, t=-2.09, P=0.038).The global efficiency of bilateral paracentral lobule and left temporal pole in middle temporal gyrus in SZ group were negatively correlated with the negative scale scores( r=-0.25, -0.25, -0.26, all P<0.05).The global efficiency of right hippocampus in SZ group was positively correlated with total scores of PANSS( r=0.23, P=0.049).The global efficiency of left middle temporal gyrus in SZ group was negatively correlated with total scores of PANSS( r=-0.23, P=0.049).The local efficiency of right paracentral lobule in SZ group was negatively correlated with the positive scale scores( r=-0.24, P=0.038). Conclusion:The brain networks of patients with first-episode paranoid schizophrenia may have regional dysfunction in the transmission efficiency and fault-tolerant ability of resting state brain functional network, and the abnormalities of efficiency may be associated with the severity of psychiatric symptoms in several brain regions.

Primary central nervous system lymphoma (PCNSL) is one of the subtypes of non-Hodgkin lymphoma, its most pathological type is diffuse large B-cell lymphoma. At present, the gold standard of PCNSL diagnosis is biopsy and pathological examination, but many patients cannot be diagnosed early due to high risk of puncture, patient compliance problems and lack of specific symptoms. PCNSL is sensitive to chemotherapy, but many patients cannot tolerate high-dose chemotherapy or develop drug resistance, leading to disease progression or recurrence. Therefore, the search and identification of biomarkers in cerebrospinal fluid for early diagnosis, efficacy judgment and prognosis monitoring are particularly important for improving the diagnosis and treatment of PCNSL.

Objective Regional homogeneity (ReHo) and functional connectivity (FC) were used to study obsessive-compulsive disorder(OCD),and to explore the mechanism of OCD in resting state.Method Resting-state functional magnetic resonance imaging (RS-fMRI) was performed in 55 patients with OCD (OCD group) and 50 normal controls (control group) matched by sex,age,nationality and education.The data and screening abnormal brain areas were analyzed and compared by DPARSFA2.3 and Rest software in OCD group.Whole brain FC analysis was performed with abnormal brain areas as seed points.Result Compared with the control group,ReHo in right thalamus (MNI:x=9,y=-24,z=6,t=4.3217) and left superior marginal gyrus (MNI:x =-45,y =-30,z =27,t =3.6320) increased and ReHo in right caudate nucleus (MNI:x=3,y=15,z=9,t=-3.1687) decreased in obsessive-compulsive disorder group,and the difference was statistically significant(P＜0.05).Using left superior marginal gyrus,fight thalamus and right caudate nucleus as seed voxels,the whole brain FC analysis showed that there were abnormal functional connections between bilateral cerebellar foot 1/2 area and left supramarginal gyrus,right thalamus and right caudate nucleus (P＜0.05) and the left supramarginal gyrus-bilateral cerebellum feet 1 area-right thalamic circuit and left supramarginal gyrus-bilateral cerebellum feet 1,2-right caudate nucleus-right thalamic circuit existed in 0CD group.Conclusion The left supramarginal gyrus-bilateral cerebellum feet 1 area-right thalamic circuit and left supramarginal gyrus-bilateral cerebellum feet 1,2-right caudate nucleus-right thalamic circuit may play an important role in the mechanism of OCD.

To investigate the presence of integrated Epstein-Barr virus (EBV) DNA in the NK/T cell lymphoma (NKTCL) ge-nome and analyze the integration information in the genome of NKTCL cell lines. Methods: PCR and in situ hybridization were used to detect EBV infection in five EBV (+) NK/T samples and four EBV (-) NK/T samples provided by the biobanks of the First Affiliated Hospi-tal of Zhengzhou University. Whole-genome DNA of the samples was sequenced and subjected to bioinformatics analysis. Whole-ge-nome sequence alignment was used to identify the EBV integration sequence. BLAST analysis was used to compare EBV fasta files of the samples and EBV fasta library. CREST software was used to extract softclip reads, filter all paired reads, and enumerate their distri-bution on chromosomes. The integrated genomics viewer (IGV) was used to compare the distribution of reads in partial regions of chromosome. PCR was used to amplify the high-frequency integration region of the EBV DNA. The amplified fragments were sanger se-quenced. Results: EBV DNA and EBER expression were detected in five EBV (+) NK/T samples but not in the four EBV (-) NK/T samples. Sequencing depth, coverage depth, proportion of coverage, and proportion of alignment all met the requirements for subsequent re-search. Sequence alignment revealed that the captured sequences were viral sequences. Filtered reads were most numerous in EBV (+) NKTCL cell line SNK, YTS, and EBV (+) nasal NKTCL tissue. The reads were non-randomly enriched in chromosome 2. EBV DNA inte-gration in the 400 bp region of chr2:30234084-30234483 caused insertion or deletion in the chr2p23.1 site. Conclusions: EBV DNA is highly integrated in the chr2p23.1 site of EBV (+) NKTCL cells and may affect the expression of related genes.

Objective: To investigate the expression and clinical significance of programmed death-ligand 1 (PD-L1), programmed death-ligand 2 (PD-L2), and their receptor programmed cell death protein 1 (PD-1) in EBV-positive T/NK lymphoproliferative disease [Epstein-Barr virus-positive T/natural killer (NK)-cell lymphoproliferative disease, EBV(+)-T/NK-LPD]. Methods: The pathological paraffin-embedded tissues of 17 patients with EBV(+)-T/NK-LPD from the First Affiliated Hospital of Zhengzhou University from January 2013 to December 2017 were collected. These patients include 12 males and 5 females, aged 10-82 years old, the average age being 29 years, 4 people in gradeⅠ, 7 in gradeⅡ, 3 in gradeⅢ, and 3 people with hydroa vacciniforme-like lymphoproliferative disorders. Immunohistochemical SP method was used to detect the expression of PD-1, PD-L1, and PD-L2 in human EBV(+)-T/NK-LPD tissues. The relationship between PD-1, PD-L1, PD-L2 expression, and clinicopathological parameters, pathological grades and prognosis were analyzed by Fisher's exact probabilities and Spearman rank correlation. Result: After statistical analysis, the results showed that in 17 cases of tissue samples, there were 12 cases with positive PD-1 expression, 6 cases with positive PD-L1 expression and 5 cases with positive PD-L2 expression. There was no significant correlation between PD-1 and PD-L2 expression and prognosis (P>0.05). PD-L1 expression showed a positive correlation with prognosis (P<0.05). There was no significant correlation between the expression of PD-L1 and PD-L2 with age, sex, as well as LDH and Ki-67 levels (P>0.05). Moreover, there was no significant correlation of PD-1 and PD-L2 expression with pathological grade (r=0.141, r=-0.149, both P>0.05). However, there was a negative correlation between the PD-L1 expression and pathological grade (r=-0.563), and the correlation between the PD-L1 ex-pression and pathological grade was statistically significant (P<0.05). Conclusions: PD-1, PD-L1, and PD-L2 are abnormally expressed in the pathological tissues of EBV(+)-T/NK-LPD. Although there was no significant correlation between the expression of PD-1 and prognosis or pathological grade, it was significantly higher in EBV+T/NK-LPD. PD-1/PD-Ls associated signaling pathway is expected to be a potential new target for EBV(+)-T/NK-LPD immunotherapy.