Traditional Chinese medicine （TCM） is widely used in the clinical management of chronic hepatitis B in China and has exhibited certain advantages in alleviating symptoms， regulating overall physiological status， and assisting in the intervention against disease progression. However， there is still a lack of a comprehensive clinical efficacy evaluation system for TCM treatment of chronic hepatitis B， with inconsistencies in the selection of evaluation indicators and limited objectivity and standardization in the assessment of syndromes and symptoms， which have limited the systematic accumulation of evidence regarding TCM efficacy and the incorporation of TCM into clinical guidelines and expert consensus statements. This article systematically reviews the current status of research on the clinical efficacy evaluation of TCM for chronic hepatitis B and analyzes the achievements made in the field of TCM therapy and integrated traditional Chinese and Western medicine therapy for chronic liver diseases in China’s national major infectious disease research programs during the periods of the Eleventh to Thirteenth Five-Year Plans. It also points out related issues that remain to be addressed and proposes a conceptual framework and specific components for constructing a TCM clinical efficacy evaluation system from the perspectives of evaluation objectives， indicator composition， and application scenarios， in order to provide a reference for the development of related standards， clinical research， and the standardization of integrated traditional Chinese and Western medicine diagnosis and treatment.

Objective:To investigate the effect of mild moxibustion on transient receptor potential vanilloid type 1(TRPV1)channel expression in primary dysmenorrhea(PD)rats and explore its mechanism in alleviating central pain sensitization.Methods:Thirty-two female non-pregnant Wistar rats were randomized into a blank group,a model group,a mild moxibustion group,and a capsazepine group,with 8 rats in each group.Except for the blank group,the other three groups used estradiol benzoate,ice-water bath,and oxytocin to establish the rat PD model of cold-dampness stagnation pattern.The interventions began on day 1 of modeling,once a day,and lasted 10 d.The mild moxibustion group received mild moxibustion at Shenque(CV8)and Guanyuan(CV4),20 min/time;in the capsazepine group,capsazepine was injected at a dose of 2 mg/(kg·bw).The abdominal pain threshold was measured 10-30 min after oxytocin injection on day 11;enzyme-linked immunosorbent assay was used to detect serum prostaglandin F2α(PGF2α)level;the expression of TRPV1,cluster of differentiation 11B(CD11B),and proto-oncogene c-Fos in the spinal dorsal horn and hypothalamus was detected by immunofluorescence and Western blotting.Results:Compared to the blank group,the model group showed a decreased pain threshold(P<0.05)and an increased serum PGF2α level with elevated TRPV1,CD11B,and c-Fos protein expression in the spinal dorsal horn and hypothalamus(P<0.05).Compared to the model group,both the mild moxibustion group and capsazepine group showed significantly increased pain thresholds(P<0.05),along with decreased serum PGF2α levels and reduced protein expression levels of TRPV1,CD11B,and c-Fos in the spinal dorsal horn and hypothalamus(P<0.05).Rat pain threshold in the capsazepine group was higher than that in the mild moxibustion group(P<0.05).Serum PGF2α level,the expression levels of CD11B and c-Fos proteins in the spinal dorsal horn,as well as TRPV1,CD11B,and c-Fos proteins in the hypothalamus of the capsazepine group were lower than those in the mild moxibustion group(P<0.05).Conclusion:Mild moxibustion at Shenque(CV8)and Guanyuan(CV4)may alleviate the central pain sensitization in PD rats by down-regulating TRPV1 channel expression in the spinal dorsal horn and hypothalamus,thus playing an analgesic effect.

Objective To investigate the effects of indirect moxibustion on the expressions of DNA methyltransferases(DNMT)and methylation of the brain-derived neurotrophic factor(BDNF)promoter region in uterine tissues of rats with primary dysmenorrhea(PD);To explore the mechanism of epigenetic regulation of indirect moxibustion on PD model rats.Methods A total of 32 female SD rats were randomly divided into blank group,model group,indirect moxibustion group and Western medicine group,with 8 rats in each group.The PD model with cold dampness stagnation syndrome was established using ice-water baths combined with estradiol benzoate and oxytocin.Starting from the first day of modeling,the indirect moxibustion group received salt-partitioned moxibustion at"Shenque"and ginger-partitioned moxibustion at"Guanyuan"for 20 min,while the Western medicine group was gavaged ibuprofen solution.Both interventions were given once a day for 10 days.On day 11,writhing responses were observed and scored after oxytocin injection,Western blot and RT-qPCR were used to detect protein and mRNA expression of BDNF,DNMT3A and DNMT3B in uterine tissue,immunohistochemical staining was used to detect the positive expressions of DNMT3A and DNMT3B in uterine tissue.The DNA methylation of BDNF promoter region in uterine tissue was detected by sulfite sequencing.Results Compared with the blank group,the writhing latency was shortened and the writhing score increased in the model group(P<0.01);the protein and mRNA expressions of BDNF,DNMT3A and DNMT3B in uterine tissue increased(P<0.01),the positive expressions of DNMT3A and DNMT3B increased(P<0.01),and the DNA methylation rate in BDNF promoter region decreased(P<0.01).Compared with the model group,the writhing latency was lengthened and the writhing score decreased in the indirect moxibustion group and Western medicine group(P<0.05,P<0.01);the protein and mRNA expressions of BDNF,DNMT3A and DNMT3B in uterine tissue decreased(P<0.05,P<0.01),the positive expressions of DNMT3A and DNMT3B decreased(P<0.01),and the DNA methylation rate in BDNF promoter region increased(P<0.01).Conclusion Indirect moxibustion at"Shenque"and"Guanyuan"may inhibit the transcription of BDNF by increasing the DNA methylation level of BDNF promoter region,and reduce the expression of BDNF,so as to relieve the pain of PD rats.

Objective:Using Mendelian randomization analysis to investigate the unidirectional causal effects of gut microbiota on gout and serum uric acid levels.Methods:The Mendelian randomization analysis was conducted using summary statistics from genome-wide association studies (GWAS). The gut microbiota was used as the exposure factor, with gout and serum uric acid levels as the outcomes, utilizing the MiBioGen Consortium, FinnGen GWAS, and CKDGen Consortium meta-analysis databases. The analysis was performed using inverse variance weighted (IVW) method, MR-Egger, and weighted median (WM) approach. Additionally, sensitivity analysis was conducted by excluding heterogeneity and horizontal pleiotropy. This study used RStudio 4.3.1 software for analysis.Results:The IVW results confirmed that 17 microbiota taxa were associated with gout, including class Verrucomicrobiaceae [ OR(95% CI)=1.162(1.004, 1.344), P=0.044], family Verrucomicrobiaceae [ OR(95% CI)=1.161(1.004, 1.344), P=0.044], genus Akkermansia [ OR(95% CI)=1.162(1.004, 1.344), P=0.044], genus Collinsella [ OR(95% CI)=1.257(1.043, 1.516), P=0.016], genus Eubacterium hallii group [ OR(95% CI)=1.226(1.022, 1.471), P=0.027], genus Howardella [ OR(95% CI)=1.094(1.001, 1.195), P=0.046], genus Ruminococcaceae UCG010 [ OR(95% CI)=1.317(1.089, 1.593), P=0.004], order Clostridiales [ OR(95% CI)=1.182(1.007,1.387), P=0.041], order Verrucomicrobiales [ OR(95% CI)=1.162(1.004, 1.344), P=0.044], class Melainabacteria [ OR(95% CI)=0.894(0.804, 0.994), P=0.038], family Streptococcaceae [ OR(95% CI)=0.851(0.727, 0.996), P=0.044], unknown family [ OR(95% CI)=0.890(0.800, 0.989), P=0.030], genus Streptococcus [ OR(95% CI)=0.836(0.710, 0.983), P=0.030], unknown genus [ OR(95% CI)=0.890(0.800, 0.989), P=0.030], genus Victivallis [ OR(95% CI)=0.857(0.736, 0.998), P=0.046], order Gastranaerophilales [ OR(95% CI)=0.890(0.800,0.989), P=0.030], and phylum Bacteroidetes [ OR(95% CI)=0.827(0.692, 0.989), P=0.037]. Additionally, 5 microbiota taxa were associated with serum uric acid levels: phylum Actinobacteria [ OR(95% CI)=0.963(0.925, 0.992), P=0.027], family ⅩⅢ [ OR(95% CI)=0.965(0.932, 1.008), P=0.035], genus Escherichia Shigella [ OR(95% CI)=1.047(1.005,1.089), P=0.034], genus Lachnospiraceae FCS020 group [ OR(95% CI)=0.974(0.941, 1.003), P=0.028], and genus Lachnospiraceae NC2004 group [ OR(95% CI)=0.966(0.943, 0.995), P=0.018]. No abnormalities in SNPs were found in the sensitivity analysis. Conclusion:An increase in the levels of class Verrucomicrobiae, family Verrucomicrobiaceae, genus Akkermansia, and genus Escherichia Shigella is associated with an increased risk of gout or serum uric acid levels, while an increase in the levels of class Melainabacteria, family Streptococcaceae, unknown family, phylum Actinobacteria, and family ⅩⅢ is associated with a decreased risk of gout or serum uric acid levels.

Objective:To evaluate the efficacy of cyclophosphamide in patients with T-cell large granular lymphocytic leukemia (T-LGLL) and the maintenance of treatment-free remission (TFR) following drug discontinuation.Methods:Clinical data were collected from 37 patients with T-LGLL who received oral cyclophosphamide at the Regenerative Medicine Clinic of the Institute of Hematology and Blood Diseases Hospital between June 2019 and March 2024. Patient clinical characteristics, treatment efficacy, and long-term TFR were analyzed.Results:The median age of the 37 patients was 60 years (range: 37-86), and 22 (59.5%) were male. Anemia was observed in 30 patients (81.1%), and 28 (75.7%) met the diagnostic criteria for secondary pure red cell aplasia. Neutropenia occurred in 15 patients (40.5%), lymphocytosis in 11 (29.7%), and thrombocytopenia in three (8.1%). Sixteen patients (43.2%) had not received prior immunosuppressive therapy (treatment-naive group), while 21 patients (56.8%) were refractory to or had relapsed after immunosuppressive treatment (refractory/relapsed group). All patients met the treatment criteria and received oral cyclophosphamide at doses of 50-100 mg/day. Among the 36 evaluable patients, hematologic remission was achieved in 25 (69.4%), with a median time of 2.0 months (range: 0.7-7.0). There was no statistically significant difference in remission rates between the treatment-naive and refractory/relapsed groups (68.5% vs. 66.7%, P=0.589). Among the 25 patients who achieved hematologic remission, 24 discontinued cyclophosphamide. With a median follow-up of 39.0 months (range: 8.0-56.0), the median TFR duration was not reached. The estimated TFR rates were (90.87± 6.16) % at 12 months and (75.72±11.04) % at 36 months. No significant difference in TFR was observed between the treatment-naive and refractory/relapsed groups ( P=0.451) . Conclusion:Oral cyclophosphamide is effective in the treatment of T-LGLL, and patients may maintain long-term TFR following drug discontinuation.

Objective:To investigate the effect of mild moxibustion on transient receptor potential vanilloid type 1(TRPV1)channel expression in primary dysmenorrhea(PD)rats and explore its mechanism in alleviating central pain sensitization.Methods:Thirty-two female non-pregnant Wistar rats were randomized into a blank group,a model group,a mild moxibustion group,and a capsazepine group,with 8 rats in each group.Except for the blank group,the other three groups used estradiol benzoate,ice-water bath,and oxytocin to establish the rat PD model of cold-dampness stagnation pattern.The interventions began on day 1 of modeling,once a day,and lasted 10 d.The mild moxibustion group received mild moxibustion at Shenque(CV8)and Guanyuan(CV4),20 min/time;in the capsazepine group,capsazepine was injected at a dose of 2 mg/(kg·bw).The abdominal pain threshold was measured 10-30 min after oxytocin injection on day 11;enzyme-linked immunosorbent assay was used to detect serum prostaglandin F2α(PGF2α)level;the expression of TRPV1,cluster of differentiation 11B(CD11B),and proto-oncogene c-Fos in the spinal dorsal horn and hypothalamus was detected by immunofluorescence and Western blotting.Results:Compared to the blank group,the model group showed a decreased pain threshold(P<0.05)and an increased serum PGF2α level with elevated TRPV1,CD11B,and c-Fos protein expression in the spinal dorsal horn and hypothalamus(P<0.05).Compared to the model group,both the mild moxibustion group and capsazepine group showed significantly increased pain thresholds(P<0.05),along with decreased serum PGF2α levels and reduced protein expression levels of TRPV1,CD11B,and c-Fos in the spinal dorsal horn and hypothalamus(P<0.05).Rat pain threshold in the capsazepine group was higher than that in the mild moxibustion group(P<0.05).Serum PGF2α level,the expression levels of CD11B and c-Fos proteins in the spinal dorsal horn,as well as TRPV1,CD11B,and c-Fos proteins in the hypothalamus of the capsazepine group were lower than those in the mild moxibustion group(P<0.05).Conclusion:Mild moxibustion at Shenque(CV8)and Guanyuan(CV4)may alleviate the central pain sensitization in PD rats by down-regulating TRPV1 channel expression in the spinal dorsal horn and hypothalamus,thus playing an analgesic effect.

Objective:To analyze the efficacy and safety of a fully biodegradable occluder for the treatment of ventricular septal defects through percutaneous and transthoracic strategies.Methods:A case series study was conducted.The clinical data of 38 pediatric patients with a ventricular septal defect treated with a fully biodegradable occluder at Central China Fuwai Hospital from January 2023 to July 2024 were retrospectively analyzed.Among these patients, 15 received the percutaneous approach(percutaneous approach group) and the other 23 adopted the transthoracic approach(transthoracic approach group).The diagnosis was confirmed by transthoracic echocardiography before operation in all patients.The percutaneous approach was defined as establishing a venous-arterial track through X-ray and then placing an occluder under the guidance of transthoracic echocardiograph.The transthoracic approach was achieved by establishing a delivery track with a special hollow bougie through a small right subaxillary incision under the real-time guidance of esophageal ultrasound and then delivery and put an occluder.The clinical data of the patients, including general characteristics, electrocardiograms, echocardiograms and the biodegradable occluder system were collected and analyzed.Categorical variables were tested using the chi-square or Fisher′s exact test.Continuous variables were verified using the t-test or Mann-Whitney U test. Results:The patients were aged (5.7±3.9) years on average, with an average weight of 19.5(14.9, 25.9) kg.There were 39.5%(15 cases) of males among the patients included.The average size of the ventricular septal defect was 4.1(4.0, 5.0) mm.A simple perimembrane ventricular septal defect was detected in 29 patients (76.3%), concomitant membranous aneurysm in 4 patients (10.5%), an intracristal ventricular septal defect in 3 patients (7.9%), and a muscular ventricular septal defect in 2 patients (5.3%).Preoperative aortic and tricuspid valve regurgitations accounted for 5.3%(2/38) and 81.6%(31/38), respectively.The average age was (9.0±3.9) years in the percutaneous approach group and (3.6±1.9) years in the transthoracic approach group.In terms of the cardiac structure, the percutaneous approach group had smaller Z values of the left atrial anterior-to-posterior diameter (-0.5±0.6 vs.0.5±1.0, P<0.01) and the left ventricular end-diastolic diameter (-0.5±1.1 vs.0.8±0.8, P<0.01), and a smaller ventricular septal defect [4.0(3.9, 4.2) mm vs.4.5(4.0, 5.5) mm, P=0.01] than the transthoracic approach group.Regarding the operation, the percutaneous approach group had a larger difference between the waist diameter of the selected occluder and the diameter of the ventricular septal defect [2.8(2.0, 3.0) mm vs.2.0(1.5, 2.5) mm, P=0.02], shorter operative time [(61.5±27.3) minutes vs.(91.5±31.4) minutes, P=0.01], and a shorter hospital stay [8(5, 9) days vs.12(9, 15) days, P<0.01] than the transthoracic approach group.Both groups achieved immediate occlusion postoperatively, with no residual shunts and no grade Ⅲ atrioventricular conduction block.Five new cases of bundle branch blocks and 1 case of trivial aortic valve regurgitation occurred in the transthoracic approach group. Conclusions:Both percutaneous and transthoracic approaches are safe and effective in interventional closure of ventricular septal defects, but the former is more applicable to slightly older or heavier patients with a smaller ventricular septal defect, who need a larger occluder.

Objective To investigate the effects of indirect moxibustion on the expressions of DNA methyltransferases(DNMT)and methylation of the brain-derived neurotrophic factor(BDNF)promoter region in uterine tissues of rats with primary dysmenorrhea(PD);To explore the mechanism of epigenetic regulation of indirect moxibustion on PD model rats.Methods A total of 32 female SD rats were randomly divided into blank group,model group,indirect moxibustion group and Western medicine group,with 8 rats in each group.The PD model with cold dampness stagnation syndrome was established using ice-water baths combined with estradiol benzoate and oxytocin.Starting from the first day of modeling,the indirect moxibustion group received salt-partitioned moxibustion at"Shenque"and ginger-partitioned moxibustion at"Guanyuan"for 20 min,while the Western medicine group was gavaged ibuprofen solution.Both interventions were given once a day for 10 days.On day 11,writhing responses were observed and scored after oxytocin injection,Western blot and RT-qPCR were used to detect protein and mRNA expression of BDNF,DNMT3A and DNMT3B in uterine tissue,immunohistochemical staining was used to detect the positive expressions of DNMT3A and DNMT3B in uterine tissue.The DNA methylation of BDNF promoter region in uterine tissue was detected by sulfite sequencing.Results Compared with the blank group,the writhing latency was shortened and the writhing score increased in the model group(P<0.01);the protein and mRNA expressions of BDNF,DNMT3A and DNMT3B in uterine tissue increased(P<0.01),the positive expressions of DNMT3A and DNMT3B increased(P<0.01),and the DNA methylation rate in BDNF promoter region decreased(P<0.01).Compared with the model group,the writhing latency was lengthened and the writhing score decreased in the indirect moxibustion group and Western medicine group(P<0.05,P<0.01);the protein and mRNA expressions of BDNF,DNMT3A and DNMT3B in uterine tissue decreased(P<0.05,P<0.01),the positive expressions of DNMT3A and DNMT3B decreased(P<0.01),and the DNA methylation rate in BDNF promoter region increased(P<0.01).Conclusion Indirect moxibustion at"Shenque"and"Guanyuan"may inhibit the transcription of BDNF by increasing the DNA methylation level of BDNF promoter region,and reduce the expression of BDNF,so as to relieve the pain of PD rats.

Objective:To compare the effect of metal prefabricated crowns and 3M350 universal resin on the dental caries of deciduous teeth.Methods:Retrospective analysis was performed on the clinical data of 89 children with proximal molar caries restoration admitted to Nantong Stomatological Hospital from January 2020 to January 2022. According to treatment methods, they were divided into observation group (metal prefabricated crowns restoration treatment, 49 cases of 49 teeth) and control group (3M350 universal resin restoration treatment, 40 cases of 40 teeth). The repair effect, occlusal function, periodontal index, treatment satisfaction and complications were compared.Results:The success rate of repair in the observation group (93.88%, 46/49) was higher than that in the control group (77.50%, 31/40), and the difference was statistically significant ( P<0.05). The maximum biting force and masticatory efficiency of the two groups after treatment were higher than those before treatment, and the observation group was higher than the control group, and the difference was statistically significant (all P<0.05). Comparison of periodontal indexes between the experimental and control groups comparison of probing depth (PD), plaque index (PLI), and bleeding index (BI) between the two groups before treatment, the differences were not statistically significant (all P>0.05); after treatment, PD, PLI, and BI were lower in both groups, and lower in the experimental group (all P<0.05). The total satisfaction of the observation group (87.76%, 43/49) was higher than that of the control group (65.00%, 26/40), and the difference was statistically significant ( P<0.05). The incidence of complications in the observation group (6.12%, 3/49) was lower than that in the control group (22.50%, 9/40), and the difference was statistically significant ( P<0.05). Conclusions:Compared with 3M350 general purpose resin, metal prefabricated crowns has better repairing effect and lower complication rate on adjacent caries of deciduous teeth, so it can be widely used in clinic.

Objective:To evaluate the efficacy of cyclophosphamide in patients with T-cell large granular lymphocytic leukemia (T-LGLL) and the maintenance of treatment-free remission (TFR) following drug discontinuation.Methods:Clinical data were collected from 37 patients with T-LGLL who received oral cyclophosphamide at the Regenerative Medicine Clinic of the Institute of Hematology and Blood Diseases Hospital between June 2019 and March 2024. Patient clinical characteristics, treatment efficacy, and long-term TFR were analyzed.Results:The median age of the 37 patients was 60 years (range: 37-86), and 22 (59.5%) were male. Anemia was observed in 30 patients (81.1%), and 28 (75.7%) met the diagnostic criteria for secondary pure red cell aplasia. Neutropenia occurred in 15 patients (40.5%), lymphocytosis in 11 (29.7%), and thrombocytopenia in three (8.1%). Sixteen patients (43.2%) had not received prior immunosuppressive therapy (treatment-naive group), while 21 patients (56.8%) were refractory to or had relapsed after immunosuppressive treatment (refractory/relapsed group). All patients met the treatment criteria and received oral cyclophosphamide at doses of 50-100 mg/day. Among the 36 evaluable patients, hematologic remission was achieved in 25 (69.4%), with a median time of 2.0 months (range: 0.7-7.0). There was no statistically significant difference in remission rates between the treatment-naive and refractory/relapsed groups (68.5% vs. 66.7%, P=0.589). Among the 25 patients who achieved hematologic remission, 24 discontinued cyclophosphamide. With a median follow-up of 39.0 months (range: 8.0-56.0), the median TFR duration was not reached. The estimated TFR rates were (90.87± 6.16) % at 12 months and (75.72±11.04) % at 36 months. No significant difference in TFR was observed between the treatment-naive and refractory/relapsed groups ( P=0.451) . Conclusion:Oral cyclophosphamide is effective in the treatment of T-LGLL, and patients may maintain long-term TFR following drug discontinuation.