Objective:To explore the impact of transcranial direct current stimulation (tDCS) on ischemic stroke survivors in terms of its association with neurotrophic factors in a person′s peripheral blood.Methods:Forty ischemic stroke survivors were randomly allocated into a control group and a treatment group, each of 20. Both groups were given routine medication and rehabilitation, while the treatment group was additionally provided with 20 minutes of tDCS daily at an intensity of 2.0mA. There were 14 sessions over two weeks. The control group received sham stimulation. Before and after the experiment, both groups were assessed using the Modified Barthel Index (MBI), the Mini-mental State Examination (MMSE), the Hamilton Depression Scale (HAMD), and the Self-rated Depression Scale (SDS). The concentrations of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the subjects′ peripheral blood were quantified using enzyme-linked immunosorbent assays (ELISAs).Results:Baseline comparisons revealed no significant disparities between the two groups in their average MBI, MMSE, HAMD, or SDS results, nor in their average BDNF or NGF levels. Post-treatment assessments indicated significant enhancements across these metrics within both groups. Notably, the treatment group then exhibited average MBI and MMSE scores superior to those of the control group, alongside a lower average HAMD score. Furthermore, elevated levels of BDNF [(108.20±36.96)pg/ml] and NGF [(2.90±1.03)pg/ml] were observed in the treatment group.Conclusion:tDCS appears to significantly enhance cognition, minimize symptoms of depression, and augment self-care ability after an ischemic stroke. These benefits are possibly mediated through the increase of neurotrophic factor levels.

Objective:To explore the clinical changes in levels of the new clinical marker serum hepatitis B virus (HBV) pregenomic RNA (pgRNA) in patients with chronic hepatitis B (CHB) with long-term antiviral therapy.Methods:100 CHB cases who were initially treated with nucleos(t)ide analogues (NAs) at Peking University First Hospital were included. The levels of alanine aminotransferase (ALT), HBV DNA, hepatitis B e-antigen (HBeAg), and hepatitis B surface antigen (HBsAg) during the follow-up period were measured. The TaqMan-based real-time quantitative PCR method was used to detect serum HBV pgRNA levels. The independent sample t-test and Mann-Whitney U test were used to compare continuous variables between groups, while Pearson's χ2 test and Fisher's exact test were used to compare categorical variables. Results:HBV pgRNA levels decreased significantly in patients who developed virological responses at 48 weeks ( n = 54) during subsequent treatment compared to those who did not ( n = 46). The HBV pgRNA level was lower in HBeAg-positive patients than in HBeAg-negative patients ( P < 0.05 or P < 0.01). Patients with higher HBV DNA and HBeAg-positivity levels at baseline had a higher HBV pgRNA level following antiviral therapy. There was no statistically significant difference in HBV pgRNA levels in patients with different HBV pgRNA levels at baseline after antiviral therapy. There was no correlation between serum HBV pgRNA and HBsAg at baseline, but there was a correlation after long-term antiviral therapy, while there was a weak correlation between HBV pgRNA and HBsAg at the fifth and ninth years of antiviral therapy ( r = 0.262, P = 0.031; r = 0.288, P = 0.008). Conclusion:HBV pgRNA levels were higher with higher HBV activity in CHB patients with long-term antiviral therapy.

Objective To investigate the effect of self-prescribed Paizhuo Qinggong Herbal Formula Granule combined with Misoprostol Tablets on uterine recovery in patients with residual intrauterine tissue after childbirth. Methods A total of 120 patients with residual intrauterine tissue after childbirth were randomly selected. According to the simple randomization method, 60 patients were assigned to control group(n=60) and experimental group(n=60). In the control group, patients were treated with a placebo of traditional Chinese medicine formula granules combined with Misoprostol Tablets. In the experimental group, patients were treated with self-prescribed Paizhuo Qinggong Herbal Formula Granule combined with Misoprostol Tablets. The clinical efficacy, syndrome score of traditional Chinese medicine, residual area of intrauterine tissue, uterine recovery indicators (sum of three uterine diameters and rate of uterine fundus descent), ultrasound blood flow parameters, matrix alloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), vaginal bleeding, adverse reactions, and uterine curettage rate were analyzed. Results The total effective rate of treatment in the experimental group was higher than that in the control group (P < 0.05). After 1 week and 2 weeks of treatment, there were statistically significant differences in the syndrome score of traditional Chinese medicine and residual area of intrauterine tissue compared with those before treatment (P < 0.05). The syndrome score of traditional Chinese medicine and residual area of intrauterine tissue in the experimental group were lower than those in the control group after 1 week and 2 weeks of treatment (P < 0.05). There were statistically significant differences in the sum of three uterine diameters between the two groups after 1 week and 2 weeks of treatment compared with those before treatment (P < 0.05). The sum of three uterine diameters in the experimental group was lower than that in the control group after 1 week and 2 weeks of treatment (P < 0.05). The rate of uterine fundus descent in the experimental group was higher than that in the control group (P < 0.05). There were statistically significant differences in the resistance index (RI), end-diastolic peak blood flow velocity (EDV), peak systolic blood flow velocity (PSV), and pulsatility index (PI) of the uterine spiral artery between the two groups after 1 week and 2 weeks of treatment compared with those before treatment (P < 0.05). The EDV and PSV in the experimental group were lower than those in the control group after 1 week and 2 weeks of treatment, while the RI and PI were higher (P < 0.05). There were statistically significant differences in the serum levels of matrix metalloproteinase-9(MMP-9) and tissue inhibitor of metalloproteinase-1(TIMP-1) between the two groups after 1 week and 2 weeks of treatment compared with those before treatment (P < 0.05). The serum levels of MMP-9 and TIMP-1 in the experimental group were lower than those in the control group after 1 week and 2 weeks of treatment (P < 0.05). The duration of vaginal bleeding in the experimental group was shorter than that in the control group, and the amount of vaginal bleeding was better in the experimental group (P < 0.05). The uterine curettage rate in the experimental group was lower than that in the control group (P < 0.05). Conclusion The combination of self-prescribed Paizhuo Qinggong Herbal Formula Granule combined with Misoprostol Tablets is effective and safe in the treatment of patients with residual intrauterine tissue after childbirth. It can improve clinical symptoms, uterine blood circulation, reduce the residual area of intrauterine tissue, promote uterine recovery, improve vaginal bleeding, reduce the rate of uterine curettage, and exert its effect by correcting the imbalance of MMP-9 and TIMP-1.

Objective:To extract and summarize the best evidence of early ambulation after anterior cervical surgery, so as to provide practical basis for early ambulation of clinical patients.Methods:The research questions were proposed based on the population, intervention, professional, outcome, setting and type of evidence (PIPOST) model. According to the "6S" model, the clinical guidelines, expert consensus, clinical decision-making, evidence summary, systematic reviews and randomized controlled trials related to "early postoperative activities of patients undergoing anterior cervical surgery" in databases such as UpToDate, British Medical Journal (BMJ) Best Practice website, Cochrane Library, China National Knowledge Infrastructure and WanFang Data were systematically retrieved. The retrieval time was from the establishment of the database to February 1, 2022. Two researchers independently evaluated the quality of the articles, and extracted and integrated the evidence of the articles meeting the quality standards.Results:A total of 10 articles were included, including two guidelines, three expert consensus, three systematic reviews, and two randomized controlled trials. It is summarized into 28 pieces of evidence and 7 dimensions, including multidisciplinary team cooperation, optimization of preoperative health education, preparation before ambulation, content of ambulation, multimodal analgesia management, nausea and vomiting management, and safety management of ambulation.Conclusions:The evidence included in this study provides a series of information for early ambulation after anterior cervical surgery. The medical and nursing staff should combine the evidence with the actual clinical situation, consider the value and expectation of the patient, comprehensively and individually evaluate the patient, and then make an early ambulation plan.

Objective:To investigate the characteristics of changes in peripheral blood regulatory T lymphocyte (Treg) levels in patients with B-cell lymphoma who received chimeric antigen receptor (CAR)-T cell immunotherapy, and the relationship between Treg levels and optimal efficacy and treatment response.Methods:The data of 23 patients with relapsed/refractory B-cell malignancies who received CD19/CD22 CAR-T cell immunotherapy in Wuhan Tongji Hospital from 2019 to 2021 were retrospectively studied. The enrolled patients were divided into complete remission (CR) group (8 cases), partial remission (PR) group (7 cases) and no response(NR) group (8 cases) according to Lugano′s revised lymphoma efficacy evaluation criteria. A total of 16 patients with B-cell lymphoma who did not receive CAR-T cell immunotherapy during the same period in Wuhan Tongji Hospital were collected as the control group.In different periods during CAR-T cell immunotherapy, multicolor flow cytometry(MFC) was used to dynamically detect peripheral blood the proportion of Treg in CD4 +T cells (Treg/CD4 +T), the proportion of lymphocytes (Treg/Lym), the proportion of Treg in white blood cells (Treg/WBC), and the absolute number of Treg (Treg#). The trend of Treg levels over time, as well as the differences in Treg levels in patients with different prognosis groups in different periods were analyzed.According to the proportion of Treg and the median level of absolute number within 1 to 15 days after CAR-T cell infusion, the patients were divided into a low-level group with 11 cases and a high-level group with 12 cases. The statistical differences in the peak value of CAR-T copy, iron protein, and IL-6 were compared between various groups. Independent samples t test, Mann-Whitney U test, Cox-Stuart trend existence test and one-way analysis of variance was used in statistical analysis. Results:In the 23 patients who received CAR-T cell immunotherapy, the mean values of Treg/CD4 +T and Treg/Lym before CAR-T cell infusion were (20.42±7.96)% and (13.61±7.13)%, respectively, which were significantly higher than that of the control group [(7.33±3.61)%, t=5.893, P<0.001; (1.91±0.90)%, t=6.53, P<0.001]. The number of Treg in the meantime was significantly lower [(1.81±1.52)/μl<(13.66±9.89)/μl, t=4.261, P<0.001]. After infusion, Treg/CD4 +T and Treg/Lym all remarkably decreased ( P<0.001),Treg/WBC increased significantly( P=0.01). The mean values of Treg/CD4 +T (12.87±1.93)%, Treg/Lym (6.35±2.84)%, and Treg/WBC (0.05±0.05)% in the patients with CR as the best response group were lower than those in the PR group [(29.68±5.49)%( P<0.01), (21.85±2.1)%( P<0.01), 0.50±0.69( P<0.05)] before CAR-T cell immunotherapy. Patients with lower mean Treg/CD4 +T within 1 to 15 days after reinfusion of CAR-T cells had higher peak CAR-T copy number ( P<0.05). Conclusion:Treg/CD4 +T and Treg/Lym were increased and then decreased during CAR-T treatment in B cell malignancies. The patients with lower proportions of Treg before infusion have favorable treatment efficacy. Besides, patients with lower Treg/CD4 +T after infusion have better CAR-T cell expansion. In the process of CAR-T cell immunotherapy, the use of MFC to dynamically monitor the proportion of Treg has certain clinical significance for the prediction of the optimal efficacy of immunotherapy and the prediction of treatment response.

ObjectiveTo investigate the virologic response to direct-acting antiviral (DAA) therapy and the changes in liver stiffness measurement (LSM), fibrosis-4 (FIB-4), and aspartate aminotransferase-to-platelet ratio index (APRI) after treatment in chronic hepatitis C (CHC) patients with different alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at baseline in a real-world setting. MethodsCHC patients who attended the outpatient service of Department of Infectious Diseases, Peking University First Hospital, from December 2017 to May 2020 were enrolled, and virologic response rate was calculated. The Wilcoxon rank-sum test was used to compare LSM, FIB-4, and APRI between groups at baseline and at 12 weeks after treatment, and the chi-square test was used for comparison of categorical data between groups. ResultsA total of 48 CHC patients were enrolled, among whom 33.3% had abnormal ALT or AST at baseline. Among these patients, the virologic response rate was 85.4% at week 4 of treatment and 100% at the end of treatment and at 12, 24, and 48 weeks after treatment, and there were significant changes from baseline to 12 weeks after treatment in LSM ［6.1 (51-12.4) kPa vs 8.6 (5.7-16.9) kPa, Z=-1.676, P=0.043］ and APRI ［0.24(0.19-0.48) vs 0.42(0.23-1.17), Z=-2.050, P=0027］. From baseline to 12 weeks after treatment, the patients with abnormal ALT or AST at baseline had significant changes in LSM ［89(5.6-13.1) kPa vs 14.4(8.0-28.2) kPa, Z=-1.679, P=0.047］ and APRI ［0.44(0.25-0.50) vs 1.29(0.99-2.09), Z=-3.427, P=0.001］. ConclusionCHC patients achieve a high sustained virologic response rate after DAA therapy, and the patients with abnormal ALT or AST at baseline tend to have more significant improvements in LSM and APRI than those without such abnormality.

Objective:To investigate the molecular mechanism of VRC01 resistance in HIV-1 subtype B′ strains isolated from a patient (DRVI01) with broadly neutralizing antibody (bNAb).Methods:Sequences of the HIV-1 subtype B′ strains isolated from patient DRVI01 were compared with those of HIV-1 subtype B′ strains that were isolated at the same time but sensitive to VRC01 antibody. Key amino acids that might affect the neutralization of VRC01 were selected according to literature reports. Effects of the selected amino acids on VRC01 neutralization were verified by site-directed mutation and sequence exchange of membrane proteins from different patients.Results:Single-point mutations of E279D and R282K in LoopD region and N460A and N463Q in V5 region reversed the viral sensitivity to VRC01 neutralization. Combined mutations in two or three above-mentioned sites significantly increased the viral sensitivity to VRC01 antibody compared with single-point mutations. Contrary to literature reports, the glycosylation site mutation of N276 had no influence on the viral sensitivity to VRC01.Conclusions:HIV-1 subtype B′ strains isolated from patient DRV01 with bNAb carried the mutations of D279 and K282 in LoopD region and N460 and N463 in V5 region, resulting in resistance to VRC01 antibody.

OBJECTIVE: To investigate the preventive effect of rock salt aerosol on the development of silicosis in rats. METHODS: The specific pathogen free adult male SD rats were randomly divided into normal control group, rock salt control group, silicosis model group and rock salt intervention group, 18 rats in each group. Rats in the silicosis model group and the salt rock intervention group were treated with silica dust at the concentration of 2 000.0 mg/m~3 by dynamic dusting method for 3 hours daily. Rats in the rock salt control group and the rock salt intervention group inhaled the rock salt aerosols with the mass concentration of 20.0 mg/m~3 for 30 minutes daily. The normal control group was not treated with the dust or rock salt aerosol. At the time points of 14, 28 and 56 days after exposure to dust or rock salt aerosol, 6 rats were randomly selected from each group and samples were collected. The pathological change of lung was observed, the total cell count in the bronchoalveolar lavage fluid(BALF) was performed, the enzyme-linked immunosorbent assay was used to detect the change of transforming growth factor-β(TGF-β) in BALF, surfactant D(SP-D) and superoxide dismutase(SOD) in lung tissue. RESULTS: The results of hematoxylin-eosin and Masson staining showed that the inflammatory changes of lung tissue and the pulmonary interstitial fibrosis in the rock salt intervention group were less severer than that in the silicosis model group. At 14, 28, and 56 days after dust exposure, the total cell counts in BALF and SP-D levels in lung tissue of rats in silicosis model group and rock salt intervention group were higher(P<0.05), the SOD activities in lung tissue were lower(P<0.05), as well as the TGF-β levels in BALF in silicosis model group were higher(P<0.05),compared with the normal control group and rock salt control group. The total cell counts and TGF-β levels in BALF, and SP-D levels in lung tissue of rock salt intervention group were lower(P<0.05), the SOD activities in lung tissue were higher(P<0.05), compared with the silicosis model group. CONCLUSION: Rock salt aerosol intervention may delay the pathogenesis of silicosis by improving the inflammatory response, regulating oxidative stress and reducing interstitial fibrosis of lungs.

Objective: To amplify and identify monoclonal antibody genes from HIV-1-infected patients. Methods: Single cell sorting was used to isolate antigen-specific single B cells. Sequence Identity Matrix and the international ImMunoGeneTics information system were used to analyze antibody variable region genes. Binding abilities were detected by enzyme linked immunosorbent assay. Neutralizing activities were tested by TZM-bl/pseudovirus assay. Results: The heavy and light chain genes of four, seven, and eleven antibodies were amplified and sequenced from three HIV-1-infected patients, respectively. They were derived from various germline genes with flexible CDR3 lengths and somatic mutations. A1 and B3 antibodies bound to HIV-1 clade B, CRF01_AE, and CRF07_BC antigens. The half maximal inhibitory concentration values of A1 and B3 against MW965 virus were 0.04 μg/ml and 37.34 μg/ml. Conclusion In this study, we acquired a lot of monoclonal antibody genes and two HIV-1 monoclonal binding and neutralizing antibodies, which would provide basic data for further research on monoclonal antibody identification.

Purpose To evaluate the quality assessed by iconographic diagnostic test system using ROBIS. Materials and Methods"Diagnostic tests, system evaluation, Meta analysis, diagnoses*test, diagnoses*trial, systematic review, meta-analysis" were used as search term to retrieve relevant literatures recorded in CBM, CNKI, Wanfang Data, PubMed, Embase, and Cochrane Library from January. 1, 2014 to December. 31, 2016. After two independent researchers screened the literature and extracted the information, the quality of included literatures was evaluated using ROBIS. Results Totally 219 articles were included in the study, including 93 Chinese literatures and 126 English literatures. The results of subgroup analysis showed that the quality difference between Chinese and English documents was statistically significant (P=0.018); the quality difference between the Chinese literatures and those of other regions was statistically significant (P<0.001); there was no statistical significance in quality difference regarding the year of publication (P=0.34). The ROBIS evaluation results showed that there were only 15 literatures (6.85%) with low-risk, including 2 Chinese literatures and 13 English literatures. Conclusion The quality evaluated by Chinese and English diagnostic test system, which is publicly published in iconographic diagnostic test from 2014 to 2016, is generally low, and the quality of literatures published by domestic scholars and in Chinese is still behind international levels. The maker of system evaluation in this field should prepare their research plans in advance and fully report them in future research, adequately obtain evidence, minimize bias in respects of document screening, information extraction, and evaluation of original research bias, and take into account of results stability, based on which the quality of system evaluation in this field should be further improved.