Objective:To explore the potential mechanism underlying IL-6 production through the TLR7 signaling pathway,which regulates Th17 cell differentiation in the context of Coxsackievirus B3(CVB3)-induced acute viral myocarditis(AVMC).Meth-ods:A total of 110 patients diagnosed with AVMC were admitted to Quanzhou First Hospital,Fujian between January 2020 and Janu-ary 2023,alongside 93 healthy volunteers.CD4+T cells were isolated from the subjects'blood,and the levels of CVB3 and the number of Th17 cells were assessed.Subsequently,CD4+T cells were infected with CVB3,and the levels of Th17 cells,IL-17,IL-21,and TNF-α were measured.After knockdown of TLR7 or treatment with TLR7 inhibitors,the differentiation of CVB3-infected CD4+T cells into Th17 cells was observed.Results:In comparison to healthy controls,AVMC patients exhibited elevated plasma levels of hsCRP,IL-17,IL-21,and TNF-α(P<0.05).The levels of CVB3 mRNA in CD4+T cells were also notably higher in AVMC patients compared to healthy controls(P<0.05).The mean viral titer in AVMC patients measured 230 PFU/ml,while no detectable virus was found in healthy volunteers(P<0.05).In CD4+T cells,the count of Th17 cells was significantly increased in AVMC patients compared to healthy volunteers(P<0.05).Moreover,the number of Th17 cells in peripheral blood CD4+T cells of AVMC patients showed a positive correlation with CVB3 virus titer(P<0.05).Following CVB3 infection,the number of Th17 cells increased compared with the control group(P<0.05),accompanied by elevated levels of IL-17,IL-21,and TNF-α in the supernatant(P<0.05).Knockdown of TLR7 and CVB3 infection in CD4+T cells significantly reduced the levels of Th17 cells(P<0.05),while the expression level of phosphorylated-activated TLR7 increased significantly after CVB3 infection of CD4+T cells compared to the control group(P<0.05).Treatment with the TLR7 inhibitor M5049 and CVB3 infection led to a significant decrease in Th17 cell levels(P<0.05).The secretion of IL-6 in CD4+T cells increased after CVB3 infection(P<0.05),and this increase was mitigated by TLR7 knockdown and CVB3 infection(P<0.05)as well as TLR7 inhibitor M5049 treatment and CVB3 infection(P<0.05).Conclusion:CVB3 activates TLR7 via phosphoryla-tion,prompting CD4+T cells to release IL-6 and undergo differentiation into Th17 cells.Consequently,TLR7 emerges as a promising therapeutic target for AVMC.

Objective:To explore the potential mechanism underlying IL-6 production through the TLR7 signaling pathway,which regulates Th17 cell differentiation in the context of Coxsackievirus B3(CVB3)-induced acute viral myocarditis(AVMC).Meth-ods:A total of 110 patients diagnosed with AVMC were admitted to Quanzhou First Hospital,Fujian between January 2020 and Janu-ary 2023,alongside 93 healthy volunteers.CD4+T cells were isolated from the subjects'blood,and the levels of CVB3 and the number of Th17 cells were assessed.Subsequently,CD4+T cells were infected with CVB3,and the levels of Th17 cells,IL-17,IL-21,and TNF-α were measured.After knockdown of TLR7 or treatment with TLR7 inhibitors,the differentiation of CVB3-infected CD4+T cells into Th17 cells was observed.Results:In comparison to healthy controls,AVMC patients exhibited elevated plasma levels of hsCRP,IL-17,IL-21,and TNF-α(P<0.05).The levels of CVB3 mRNA in CD4+T cells were also notably higher in AVMC patients compared to healthy controls(P<0.05).The mean viral titer in AVMC patients measured 230 PFU/ml,while no detectable virus was found in healthy volunteers(P<0.05).In CD4+T cells,the count of Th17 cells was significantly increased in AVMC patients compared to healthy volunteers(P<0.05).Moreover,the number of Th17 cells in peripheral blood CD4+T cells of AVMC patients showed a positive correlation with CVB3 virus titer(P<0.05).Following CVB3 infection,the number of Th17 cells increased compared with the control group(P<0.05),accompanied by elevated levels of IL-17,IL-21,and TNF-α in the supernatant(P<0.05).Knockdown of TLR7 and CVB3 infection in CD4+T cells significantly reduced the levels of Th17 cells(P<0.05),while the expression level of phosphorylated-activated TLR7 increased significantly after CVB3 infection of CD4+T cells compared to the control group(P<0.05).Treatment with the TLR7 inhibitor M5049 and CVB3 infection led to a significant decrease in Th17 cell levels(P<0.05).The secretion of IL-6 in CD4+T cells increased after CVB3 infection(P<0.05),and this increase was mitigated by TLR7 knockdown and CVB3 infection(P<0.05)as well as TLR7 inhibitor M5049 treatment and CVB3 infection(P<0.05).Conclusion:CVB3 activates TLR7 via phosphoryla-tion,prompting CD4+T cells to release IL-6 and undergo differentiation into Th17 cells.Consequently,TLR7 emerges as a promising therapeutic target for AVMC.

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

Objective: To provide high-quality clinical evidence of the efficacy of Tibetan medicine Honghua Ruyi (HHRY) pills for endometriosis-associated dysmenorrhea. Methods: This study constitutes a multicenter, randomized, double-blind, placebo-controlled trial encompassing a three-menstrual cycle intervention followed by a three-menstrual cycle follow-up period. A total of 164 eligible females with endometriosis-associated dysmenorrhea were randomly divided into HHRY pills and placebo groups in a 1:1 ratio. The primary outcome included dysmenorrhea symptoms assessed using Visual Analog Scale (VAS) scores and quality of life, whereas the secondary outcome measures included the maximum VAS for non-menstrual pelvic pain, duration of pain episodes (in days), frequency and quantity of the consumption of ibuprofen sustained-release capsules (or other non-steroidal anti-inflammatory drugs), and days off work/study for staff/student due to dysmenorrhea, ovarian cyst, and/or pelvic nodule size. The safety was monitored throughout the treatment period. All the analyses were based on the intention-to-treat principle. For continuous outcomes, simple or multiple linear regressions were used to estimate the differences between the HHRY pills and placebo groups, with categorical data expressed as the number and percentage of occurrences. Differences were compared using the chi-square test or Fisher's exact test. The predefined analysis was adjusted for concomitant treatment, a variable considered to be associated with outcomes but unaffected by treatment allocation. Estimates of treatment effects were reported with 95% confidence intervals. Two-tailed P values ≤ .05 were considered statistically significant. Conclusion Positive results from this trial, upon completion would provide robust evidence for the efficacy and safety of HHRY pills in treating dysmenorrhea in patients with endometriosis.

Objective To investigate the efficacy of entecavir (ETV) versus tenofovir disoproxil fumarate (TDF) and the treatment measures for poor response in previously untreated chronic hepatitis B (CHB) patients with high viral load. Methods A total of 165 CHB patients who received antiviral therapy and met the inclusion criteria in Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, from June 2016 to July 2021 were enrolled. The patients enrolled had a baseline HBV DNA level of > 6lg copies/ml and were previously untreated CHB patients who had used ETV or TDF for 48 weeks, and quantitative real-time PCR was used to measure HBV DNA. Virologic response rate was calculated after 48 weeks of treatment; a logistic regression analysis was used to investigate the influencing factors for the response of HBV DNA < 500 copies/mL and HBV DNA < 100 copies /mL at 48 weeks; a stratified analysis was performed to compare the virologic response rate of HBV DNA < 500 copies /ml and HBV DNA < 100 copies/ml after 48 weeks between the patients with different ages, sexes, baseline HBV DNA levels, baseline alanine aminotransferase (ALT) levels, types of first-line medication, and HBeAg statuses. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups, and the binary logistic regression model was used for multivariate analysis. Results After 48 weeks of treatment, 85.5% (141/165) of the patients achieved an HBV DNA load of < 500 copies/mL, and 66.1% (109/165) of the patients achieved an HBV DNA load of < 100 copies /mL, with no significant difference in treatment outcome between the ETV group and the TDF group. The multivariate logistic regression analysis showed that sex( OR =2.793, 95% CI : 1.197-6.517), baseline HBV DNA( OR =0.369, 95% CI : 0.142-0.959), baseline ALT( OR =4.556, 95% CI : 1.770-11.732), and baseline HBeAg( OR =0.120, 95% CI : 0.033-0.429) were influencing factors for complete virologic response(all P < 0.05). For the patients with normal ALT (≤40 U/L) at baseline, 75.6% (34/45) achieved an HBV DNA load of < 500 copies/mL after 48 weeks of treatment, and 53.3% (24/45) achieved an HBV DNA load of < 100 copies/mL, with no significant difference in treatment outcome between the ETV group and the TDF group. For the patients with abnormal ALT (> 40 U/L) at baseline, 89.2% (107/120) achieved an HBV DNA load of < 500 copies/mL after 48 weeks of treatment, and the proportion of such patients in the TDF group was significantly higher than that in the ETV group (96.1% vs 84.1%, χ 2 =4.386, P =0.036); 70.8% (85/120) achieved an HBV DNA load of < 100 copies/mL, the proportion of such patients was no significant difference between the TDF group and the ETV group (78.4% vs 65.2%). The response of HBV DNA < 100 copies/ml of the normal baseline ALT group and the abnormal baseline ALT group, there were no significant differences between the patients aged≤30 years and aged > 30 years (77.8% vs 47.2%, 85.2% vs 66.7%). For the patients who did not achieve complete virologic response (HBV DNA ≥100 copies/mL) after 48 weeks of treatment, 87.9% (29/33) achieved complete virologic response after the original treatment regimen was prolonged for 48 weeks, and 100% (9/9) of the patients achieved complete virologic response after switching to or adding the first-line nucleos(t)ide analogues (NUCs) without cross-resistance sites with the original regimen for another 48 weeks. Conclusion The patients aged > 30 years should receive antiviral therapy as early as possible, regardless of viral load and ALT level, especially those with a family history of liver cirrhosis or hepatocellular carcinoma; the patients aged ≤30 years who have a normal ALT level and a high viral load should consider initiating antiviral therapy after providing informed consent. For the patients with poor response after 48 weeks of treatment, first-line NUCs without cross-resistance sites with the original regimen should be switched to or added in time.

Adult ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use* ; COVID-19/drug therapy* ; Humans ; Pyridones/therapeutic use* ; Treatment Outcome

Objective:To retrospectively analyze the risk factors for the development of liver cancer in patients with hepatitis B-related liver cirrhosis (LC) treated and fully managed with long-term nucleos(t)ide analogues (NAs).Methods:The study subjects were derived from the follow-up cohort of chronic hepatitis B and liver cirrhosis who received antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Guangxi Medical University from February 2004 to September 2019. LC patients who met the inclusion criteria were enrolled. The life-table method was used to calculate the incidence of liver cancer. Multivariable Cox regression model was used to analyze the risk factors that may affect the development of liver cancer in patients with LC. A subgroup analysis was conducted in liver cirrhotic patients who developed liver cancer to evaluate the effectiveness of antiviral treatment compliance. The 2 test was used for rate comparison. Results:The median follow-up time of 198 LC cases treated with NAs was 6.0 years (1.0-15.3 years). By the end of the visit: (1) 16.2% (32/198) of LC patients had developed liver cancer, and the cumulative incidence of liver cancer in 1, 3, 5, 7, and 9 years were 0, 8.9%, 14.3%, 18.6%, and 23.4%, respectively, with an average annual incidence of 3.1%. Among the 32 cases with liver cancer, 68.7% had developed small liver cancer (22/32). (2) Univariate Cox model analysis showed that the development of liver cancer was related to four factors, i.e., the presence or absence of LC nodules, whether the baseline was first-line medication, the family history of liver cancer, and patient compliance. The results of multivariate Cox model analysis showed that poor patient compliance and baseline non-first-line medication were risk factors for liver cancer. (3) The results of log-rank test subgroup analysis showed that the 5-year cumulative incidence of liver cancer in patients with hardened nodules was significantly higher than that of patients without hardened nodules (21.7% vs. 11.5%, P = 0.029). The 5-year cumulative incidence of liver cancer in patients with non-first-line drugs was significantly higher than that of patients with first-line drugs (22.0% vs.8.2%, P = 0.003). The 5-year cumulative incidence of liver cancer in patients with poor compliance was significantly higher than that of patients with good compliance (21.3% vs. 12.7%, P = 0.014). The 5-year cumulative incidence of liver cancer in patients with a family history of liver cancer was significantly higher than that of patients without a family history of liver cancer (22.3% vs. 8.1%, P = 0.006). (4) Compared with patients with poor compliance, patients with good compliance had higher HBV DNA negative serconversion rate (98.7% vs. 87.8%, P = 0.005), and a lower virological breakthrough rate (12.1% vs. 29.3%, P = 0.007). Conclusion:The long-term NAs antiviral therapy can reduce the risk of liver cancer, but it cannot completely prevent the development of liver cancer, especially in patients with a family history of liver cancer and baseline hardened nodules (high risk of liver cancer). Furthermore, the complete management can improve patient compliance, ensure the efficacy of antiviral therapy, and reduce the risk of liver cancer development, so to achieve secondary prevention of liver cancer, i.e., early detection, diagnosis and treatment.

Objective:To retrospectively analyze the serological, virological, biochemical, liver histological status and clinical outcomes in HBeAg-negative chronic hepatitis B (CHB) patients with low HBV viral load, and to explore the necessity of antiviral therapy for these patients.Methods:A total of 99 HBeAg-negative CHB patients with HBV DNA level < 4 lg copies/ml who performed liver biopsy at the baseline were enrolled from the follow-up cohort. Among them, 23 cases received the second liver biopsy during follow-up. The relationships among the degree of inflammation and fibrosis of liver tissues, the status of HBsAg and HBcAg, age, gender, family history, HBV DNA load, serological markers and other indicators were analyzed. The pathological differences between two liver biopsy examinations were compared. The effect of nucleos(t)ide analogues (NAs) treatment on patient’s clinical outcomes were analyzed. For multivariate analysis, a binary logistic regression model was performed. Log-rank test was used to compare the cumulative incidence of hepatocellular carcinoma (HCC) in NAs-treated and non-NA streated patients.Results:Baseline liver histology status showed that 58.6% (58/99) patients had obvious liver tissue damage in their baseline liver tissue pathology (G≥2 and /or S≥2). Univariate logistic regression analysis showed that a liver cirrhosis (LC) family history, a HBsAg-positive family history, baseline alanine aminotransferase and aspartate aminotransferase levels were positively correlated factors for liver tissue damage. Multivariate logistic regression analysis showed that a LC family history was the main risk factor for liver tissue damage. Twenty-three cases had received a second liver biopsy after an interval of 4.5 years. In 10 untreated cases, the second liver biopsy results showed the rate of obvious liver tissue damage (G≥2 and/ or S≥2) increased from 50.0% to 90.0%. In the other 13 cases who received NAs treatment, the second liver biopsy showed improvement in liver histology, and the rate of obvious liver tissue damage decreased from 61.5% to 46.2%. The 5-year HCC cumulative incidence in non-NAs-treated patients was significantly higher than that of in NAs-treated patients (17.7% vs. 3.8%, P = 0.046). Conclusion:For most HBeAg-negative CHB patients with low viral load, liver tissue pathology result suggests that it meets the indications for antiviral therapy, especially in patients with a LC familial history. Without antiviral therapy, liver tissue damage for these patients will progressively worse with the high incidence of HCC. Therefore, it is suggested that antiviral therapy should be started as soon as possible for the HBeAg-negative CHB patients with low viral load regardless of the alanine aminotransferase level, especially in patients over 30 years-old with a LC or HCC family history.

Objective To evaluate the dietary quality of children aged 3 to 6 years during the kindergarten period in Lanzhou City using the Dietary Balance Index (DBI). Methods Based on kindergarten grades and geographical locations, 304 recipes for different semesters from 2014 to 2017 in 40 kindergartens in Lanzhou City were randomly selected with a sampling ratio of 5％(291 recipes with no recipes 13 copies) as the research object. Adjusted DBI indicators for children aged 3 to 6 years were used to evaluate the dietary quality of the recipes during the kindergarten period in the sample. Using the Kruskal-Wallis H rank-sum test, the food consumption rates and DBI evaluation results of the kindergartens in Lanzhou City were analyzed. Results Results of the sub-group diet scores that were close to the recommended intake (DBI scores between-2 to 2) showed that cereals, fresh vegetables, nuts and beans, fish, shrimp, eggs, and snacks accounted for the ideal intake of more than 80％of all the recipes. The diet scores of fruits, meat, and processed products ranged from 50％to 80％, and that for milk accounted for only 26.8％. Analyzing the type of food intake showed that the proportion of recipes that included eating more than six types of food per day was 98.3％. Analyzing by kindergarten level and year showed that the overall dietary quality problems with the studied recipes were mainly caused by insufficient intake and dietary imbalance, and the difference was statistically significant. Among them, the lack of intake in 2017 and the degree of dietary imbalance were greater compared to the other years. The level of insufficiency and dietary imbalance in the third-grade kindergartens were higher than those in the first- and second-grade kindergartens. Dietary pattern A recipes accounted for 63.6％ of the kindergarten recipes, and there were no recipes for dietary patterns C, F, G, H, and I. Conclusion The dietary quality problems of kindergartens in Lanzhou City were mainly reflected in the inadequate dietary intake and dietary imbalance. The supervision of dietary quality by kindergartens should be strengthened and the concept of a balanced diet should be promoted. The dietary management of third-grade kindergartens should be simultaneously strengthened.

Objective To compare the therapeutic effect of conventional treatment and conventional treatment plus external application of Shuangbai Powder for patients with wounded limb injured by venomous snake. Methods One hundred patients bitten by venomous snake were randomized into treatment group and control group, 50 cases in each group. The control group was given conventional treatment including repeatedly washing the wound with hydrogen peroxide, debriding the wound, letting blood and draining toxicity, local blocking with chymotrypsin, wet packing the wounded limb with magnesium sulfate, and injection with anti-venomous serum, tetanus antitoxin, antibiotics, furosemide and energy mixture. The treatment group was given external application of Shuangbai Powder on the basis of the treatment for the control group. Both groups were given the comprehensive nursing of psychological nursing, wound nursing, dietary nursing, defecation nursing and functional nursing. The swelling-subsiding time for the wounded limb and pain scores of visual analogue scale (VAS) in the two groups were compared. Results(1) After treatment, swelling-subsiding time for the wounded limb of the treatment group was shorter than that of the control group, the difference being statistically significant (P < 0.05). (2) After treatment for 4 days and at the end of the treatment, VAS scores of the two groups were decreased compared with those before treatment(P < 0.05), and the decrease of VAS scores in the treatment group after treatment for 4 days was superior to that in the control group (P < 0.05). Conclusion The conventional treatment plus external application of Shuangbai Powder is an effective therapy for patients with wounded limb injured by venomous snake by shortening swelling-subsiding time and relieving pain for the wounded limb .