AimTo evaluate the efficacy and safety of Jinghua Weikang Capsule (JWC) combined with amoxicillin-furazolidone triple/quadruple therapies in the rescue treatment of drug-resistant H. pylori infection.MethodsPatients who failed H. pylori eradication therapy at least once were enrolled and randomly assigned into four groups (1:1:1:1), as follows: The control group received 20 mg rabeprazole, 1,000 mg amoxicillin, 220 mg bismuth potassium citrate, and 100 mg furazolidone twice daily (b.i.d.) for 14 days; Group A received 240 mg JWC b.i.d. combined with 20 mg rabeprazole, 1,000 mg amoxicillin, and 100 mg furazolidone b.i.d. for 14 days; Group B received the same regimen as Group A for 14 days, followed by an additional 14 days of 240 mg JWC b.i.d.; and Group C received 240 mg JWC b.i.d. combined with 20 mg rabeprazole, 1,000 mg amoxicillin, 220 mg bismuth potassium citrate, and 100 mg furazolidone b.i.d. for 10 days. The primary outcome was H. pylori eradication at 4 weeks after treatment.ResultsFour hundred eighty-eight patients were included in this study. The intention-to-treat (ITT) eradication rates in the four groups were 85.2, 73.8, 78.7 and 75.4% (p = 0.136), while the modified intention-to-treat (MITT) eradication rates were 92.0, 84.9, 88.9 and 86.8% (p = 0.398), respectively. And the per-protocol (PP) eradication rates were 92.5, 85.4, 87.9 and 86.7% (p = 0.405), respectively. The eradication rates were comparable among the four groups. No statistically significant differences in eradication rates were observed between each of the three treatment groups and the control group (all p > 0.05). The eradication rate of H. pylori in group B demonstrated non-inferiority compared with the control group (p = 0.0415; 90% CI, −0.0965 to 0.0336). The four groups exhibited similar frequencies of overall adverse events (9.84, 5.74, 6.56%, 2.46%, p = 0.112).ConclusionThe eradication rate of the JWC-containing regimen demonstrated no statistically significant difference compared with bismuth-containing quadruple therapy in the rescue treatment of H. pylori infection. The prolonged JWC treatment regimen exhibited non-inferiority in eradication rates. JWC-containing therapies can effectively reduce the incidence of adverse reactions and significantly alleviate certain clinical symptoms.Clinical trialhttps://clinicaltrials.gov/, identifier ChiCTR1800019326.

Objective To modify more accurate clinical and viral indicators and establish the new model for differentiating the different stages of chronic hepatitis B virus (HBV) infection based on liver histopathological changes. Methods The clinical and liver pathology data of chronic hepatitis B (CHB) patients undergoing liver biopsy were collected for retrospective analysis in the test and validation group. The area under the curve (AUC) of the receiver operating characteristic (ROC) was used to evaluate the diagnostic value for differentiating the different stages of chronic HBV infection. Results A total of 118 patients and 73 patients who met the diagnostic and exclusion criteria were selected as the test group and validation group. Multivariate analysis showed that HBeAg independently correlated with the IT and IC stages. The cutoff value of HBeAg used to quantitatively differentiate between IT and IC was 1335 and the AUC was 0.921 (95% confidence interval (CI): 0.836 to 0.971). A new prediction model of IT stage was established by using three indicators including HBeAg, HBsAg and HBV DNA. The AUC is 92.3% (95% CI: 86.4-98.2, P<0.001) using this prediction model. The sensitivity and specificity are 85.5% and 95.2%. Conclusions The high levels of HBeAg rather than HBeAg positive might help to identify patients with the “true” IT stage. A predictive model for immune tolerance stage are established by combining three indicators. The new prediction model has significantly reduced the error rate compared with others standards.

Abstract Background Skeletal muscle dysfunction is a prevalent and serious complication of chronic obstructive pulmonary disease (COPD), presenting significant clinical challenges. Despite its commonality, the specific molecules and the mechanisms at play in COPD-related muscle dysfunction remain elusive, leaving a gap in effective early diagnostic and therapeutic strategies. Methods Our study aims to pinpoint the molecular signatures of skeletal muscle dysfunction in COPD by developing both in vivo and in vitro research models, deploying cutting-edge high-throughput sequencing techniques, and employing sophisticated algorithms for dimensionality reduction analysis. Results In our COPD rat models, we observed profound structural changes in the skeletal muscles, such as fiber disruption, mitochondrial shrinkage, and a decrease in mitochondrial count. Notably, we identified DBP—a key molecule—as being markedly overexpressed in COPD models, both in vivo and in vitro. Conclusion Our findings underscore the significant impact COPD has on skeletal muscle structure, leading to muscle wasting, fiber damage, and mitochondrial deterioration. The identification of DBP as a critical molecular marker sheds light on the potential pathways of skeletal muscle impairment in COPD and opens the door for new diagnostic and therapeutic interventions.

Background: ALA-PDT has been widely used in mild to moderate acne vulgaris worldwide. However, very few studies used riboflavin-PDT to treat acne vulgaris. Objective: To investigate the efficacy and adverse events of riboflavin-PDT to treat mild to moderate facial acne, and compare it with ALA-PDT on a non-inferiority basis. Methods: 33 eligible patients were enrolled, and 30 patients completed follow-up. Either side of the face was assigned randomly to riboflavin or ALA blue-light-PDT. Patients received 3 sessions of PDT in 1-week intervals and were followed up at weeks 4, 6, and 10. Results: Both ALA and riboflavin-PDT significantly reduced non-inflammatory and inflammatory lesions at weeks 4, 6, and 10 compared to baseline (P all <0.001). For the primary outcome, the difference in the improvement rate of total lesions between the Ribo and ALA side was 2.6 % (-4.3 %, 12.5 %; p = 0.71), which didn't reach the inferiority margin. Patients described greater in-treatment pain and burning sensation (P < 0.001), more prominent post-treatment erythema (P = 0.003), hyperpigmentation (P < 0.001), and desquamation (P = 0.006) on the ALA side than on riboflavin side. Conclusion: The efficacy of riboflavin-PDT was comparable to that of blue-light ALA-PDT in treating mild to moderate acne vulgaris. Riboflavin-PDT had fewer in-treatment and post-treatment adverse events than ALA-PDT.

What is already known about this topic?Multi-drug resistant tuberculosis (MDR-TB) is a critical global public health problem.What is added by this report?Sputum cultures and lung images show a strong association with treatment outcomes, serving as a multi-dimensional approach to identify MDR-TB patients with poor outcomes.What are the implications for public health practice?The results imply that funds and policy investments should be increased by early monitoring of MDR-TB patients, especially regarding imaging and sputum bacterium. By informing physicians on changes to the therapeutic schedule, treatment outcomes can be improved.

Background: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. Steroid 5 alpha-reductase 3 (SRD5A3) was reported to be up-regulated in many types of cancer. However, its expression and role in HCC remains to be elucidated. We aim to evaluate the significance of SRD5A3 expression in HCC by using analysis of a public dataset from The Cancer Genome Atlas (TCGA). Methods: The relationship between clinical pathologic features and SRD5A3 were analyzed with the Kolmogorov‐Smirnov test and the logistic regression. Cox regression and the Kaplan-Meier method were used to assess the clinicopathologic characteristics associated with overall survival (OS) in TCGA patients. In addition, GSEA was used to predict potential hallmarks associated with different expression of SRD5A3 on transcriptional sequences from TCGA database. Results: SRD5A3 was highly expressed in HCC tumor tissue compared to normal tissue. A total of 184 upregulated DEGs (differentially expressed genes) and 58 downregulated DEGs were identified between high expression and low expression of SRD5A3. Among them, 22 hub genes mainly belonging to the keratin and MUC family demonstrated by connectivity degree in the PPI network were screened out. Kaplan-Meier method showed that HCC patients in the high SRD5A3 expression group had poorer overall survival (OS, HR=2.26(1.58-3.24), p<0.001). In addition, cell cycle mitotic, cell cycle checkpoints, mitotic nuclear division, Q-glycan processing, protein O-linked glycosylation were differentially enriched in the high SRD5A3 expression phenotype pathway. In addition, SRD5A3 expression level has significant correlations with infiltrating levels of Th17 (R = -0.238, p < 0.001), Cytotoxic cells (R = -0.234, p < 0.001) and Th2 cells (R = 0.258, p < 0.001) in HCC. Conclusions: High expression of SRD5A3 was significantly correlated with poor prognosis in HCC patients. It may be a potential biomarker in HCC.

Traditional Chinese medicine (TCM) is widely accepted and prescribed in China alongside Nucleoside analogs (NAs). In this double-blind, placebo-controlled, randomized, multi-center trial, we evaluated whether entecavir (ETV) plus TCM formulas Tiao-Gan-Yi-Pi granule (TGYP) and Tiao-Gan-Jian-Pi-Jie-Du granule (TGJPJD) increase the rate of hepatitis B e antigen (HBeAg) loss in Chinese patients. 596 eligible participants were randomly assigned, in a 1:1 ratio, to two study groups in this 108-week trial: The experiment group was assigned ETV plus the TCM formula. The control group was assigned ETV plus a TCM placebo. We compared the rate of HBeAg loss by the end of week 108 between the two arms as the primary outcome. Secondary outcomes included hepatitis B surface antigen (HBsAg) level, proportion of undetectable HBV-DNA, and liver enzymes (ALT, AST, GGT) at week 108. The combination therapy achieved superior HBeAg loss at 108 weeks, without additional adverse events. The rate of HBeAg loss at week 108 was 37.54% (95% CI 31.9–43.2%) in the experiment group and 27.21% (95% CI 22.0–32.4%) in the control group. There was a statistically significant difference between the two arms of 10.33% (95% CI 8.4–12.3%, p = 0.008). The DNA loss rate, serum HBsAg level, and liver enzymes were similar between the groups by the end of 108th week. Combining the Chinese herbal formula with ETV therapy demonstrated superior HBeAg clearance compared with ETV monotherapy. This finding indicates that this combined therapy could produce an improved therapeutic effect and safety profile. ChiCTR-TRC-12002784 (Chinese Clinical Trial Registry).

Lonicerae Japonicae Flos (LJF), a kind of traditional Chinese medicines (TCMs), has functions of detoxifying and evacuating heat. In the study, a method based on ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS) was developed for the chemical constituent analysis of organic acids, flavonoids, iridoids and new-generated compounds in sulfur-fumigated LJF (SF-LJF). Based on the accurate mass measurement (< ± 5 ppm), chromatographic behavior and diagnostic product ions (DPIs), 113 constituents were unambiguously or tentatively characterized from SF-LJF extract, including 46 chlorogenic acids, 19 flavonoids, 29 iridoid glycosides and 19 newly-generated compounds (including 17 sulfur-containing derivatives). In addition, 5-CQA (5-caffeoylquinic acid, chlorogenic acid) was chosen to be sulfur-fumigated for the result validation. It was found that the most significant change of LJF after sulfur fumigation was the occurrence of sulfate or sulfite esterification reactions, which resulted in the emergence of many new sulfur-containing components. Our results demonstrated that the established method was a useful and efficient analytical tool to comprehensively characterize the material basis of SF-LJF, and also an excellent guidance of quality control about LJF.

Ascites is one of the most common complications of cirrhosis. Umbilical therapy with traditional Chinese medicines has been increasingly prescribed to treat cirrhotic ascites. However, high-quality evidence from clinical trials supporting such application of traditional Chinese medicines remains limited. Therefore, we designed a clinical trial to evaluate the efficacy and safety of umbilical therapy with the Lishui Xiaogu cataplasm formulation applied to treat cirrhotic ascites.

The domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (e degrees integral e,ec > Se"3/4e cent uc(2)', TGYP) or Tiaogan-Jianpi-Jiedu Granule (e degrees integral e,eae"3/4e ae pound'e cent uc(2)', TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate. The study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via central randomization system: experimental group (EG) and control group (CG). Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily) plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1), and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2). Subjects in CG received CHM Granule placebo plus ETV tablet (0.5 mg per day) for 108 weeks throughout the trial. The assessments of primary outcomes (HBV serum markers and HBV-DNA) were conducted by a third-party College of American Pathologists (CAP) qualified laboratory. Adverse effects were observed in the hospitals of recruitment. The study was designed to compare the curative effect of CM plus ETV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as "a valuable endpoint". We believe this trial could provide a reliable status for patients' "journey" towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23).

Ficolin-2 (FCN2) is an innate immune pattern recognition molecule that can activate the complement pathway, opsonophagocytosis, and elimination of the pathogens. The present study aimed to investigate the association of the FCN2 gene single nucleotide polymorphisms (SNPs) with susceptibility to pulmonary tuberculosis (TB). A total of seven SNPs in exon 8 (+6359 C>T and +6424 G>T) and in the promoter region (-986 G>A, -602 G>A, -557 A>G, -64 A>C and -4 A>G) of the FCN2 gene were genotyped using the PCR amplification and DNA sequencing methods in the healthy controls group (n = 254) and the pulmonary TB group (n = 282). The correlation between SNPs and pulmonary TB was analyzed using the logistic regression method. The results showed that there were no significant differences in the distribution of allelic frequencies of seven SNPs between the pulmonary TB group and the healthy controls group. However, the frequency of the variant homozygous genotype (P = 0.037, -557 A>G; P = 0.038, -64 A>C; P = 0.024, +6424 G>T) in the TB group was significantly lower than the control group. After adjustment for age and gender, these variant homozygous genotypes were found to be recessive models in association with pulmonary TB. In addition, -64 A>C (P = 0.047) and +6424 G>T (P = 0.03) were found to be codominant models in association with pulmonary TB. There was strong linkage disequilibrium (r2 > 0.80, P < 0.0001) between 7 SNPs except the -602 G>A site. Therefore, -557 A>G, -64 A>C and +6424 G>T SNPs of the FCN2 gene were correlated with pulmonary TB, and may be protective factors for TB. This study provides a novel idea for the prevention and control of TB transmission from a genetics perspective.

A major challenge in pulmonary tuberculosis (TB) control is early and accurate diagnosis of sputum smear negative pulmonary TB (SSN-PTB). The patients with SSN-PTB have to wait for a longer period of time before receiving proper treatment than sputum smear positive pulmonary TB (SSP-PTB) patients due to delay in diagnosis. The purpose of this study is to discover potential serum protein biomarkers for SSN-PTB. Surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF MS) combined with weak cation exchange (WCX) magnetic beads was used to screen serum samples from SSN-PTB patients (N = 66), SSP-PTB patients (N = 49), and healthy volunteers (N = 80). The serum protein profiles were analyzed with Biomarker Wizard system. A classification model was established using Biomarker Pattern Software (BPS). Fifty-eight protein peaks were identified to exhibit significant differences between SSN-PTB, SSP-PTB and healthy control groups (P < 0.05), among which 6 peaks were found to be down-regulated, while 10 peaks were up-regulated gradually in the healthy control, SSN-PTB, and SSP-PTB groups. Twenty-three discriminating m/z peaks were detected between SSN-PTB patients and healthy controls (P < 0.01, Fold ≥ 1.5). The classification tree combined with three protein peaks (2747.0, 4480.0, and 9410.1 Da) could distinguish SSN-PTB patients from healthy controls with a sensitivity of 83.33% and a specificity of 82.50%. Early diagnosis of SSN-PTB disease is critical in order to reduce morbidity and mortality associated with TB. The study will help to clarify the role of differential proteins in the pathogenesis of TB.

Background The present study aimed to investigate the genetic polymorphisms in exon 4 of the NOD2 gene in tuberculosis patients and healthy controls, in order to clarify whether polymorphisms in the NOD2 gene is associated with tuberculosis. Methods A case-control study was performed on the Chinese Han, Uygur and Kazak populations. Exon 4 of the NOD2 gene was sequenced in 425 TB patients and 380 healthy controls to identify SNPs. Results The frequency of T/G genotypes for the Arg587Arg (CGT → CGG) single nucleotide polymorphism (SNP) in NOD2 was found to be significantly higher in the Uygur (34.9%) and Kazak (37.1%) populations than the Han population (18.6%). Also, the frequency of G/G genotypes for the Arg587Arg SNP was significantly higher in the Uyghur (8.3%) and Kazak (5.4%) populations than the Han population (0.9%). Meanwhile, no significant difference was found in the Arg587Arg polymorphism between the tuberculosis patients and healthy controls in the Uyghur and Kazak populations ( P > 0.05) whereas, a significant difference was observed in the Arg587Arg polymorphism between the tuberculosis patients and healthy controls in the Han population ( P < 0.01). The odd ratio of 2.16 (95% CI = 1.31-3.58; P < 0.01) indicated that the Arg587Arg SNP in NOD2 may be associated with susceptibility to tuberculosis in the Chinese Han population. Conclusions Our study is the first to demonstrate that the Arg587Arg SNP in NOD2 is a new possible risk factor for tuberculosis in the Chinese Han population, but not in the Uyghur and Kazak populations. Our results may reflect racial differences in genetic susceptibility to tuberculosis.

Mannose receptor is a member of the C-type lectin receptor family involved in pathogen molecular-pattern recognition, and plays a critical role in shaping host immune response.Single nucleotide polymorphisms (SNPs) in the MRC1 gene may affect expression levels and differences in the structure and function of proteins in different individuals, thereby affecting individual susceptibility to pulmonary tuberculosis.However, to date, MRC1 polymorphisms associated with susceptibility to pulmonary tuberculosis have not yet been reported.The present study aimed to investigate potential associations of SNPs in the MRC1 gene with pulmonary tuberculosis in a Chinese population.Six SNPs (G1186A, G1195A, T1212C, C1221G, C1303T and C1323T) in exon 7 of the MRC1 gene were genotyped using the PCR and DNA sequencing methods in the pulmonary tuberculosis patients and the healthy controls.Linkage disequilibrium analysis was performed between polymorphic sites.The study found that the allele frequency of G1186A (rs34039386) of the MRC1 gene in a Chinese population was higher in the pulmonary tuberculosis group than the healthy control group.There was a significant difference in frequency distribution between the two groups (P = 0.037; OR = 0.76; 95% CI, 0.58-0.98).Genotypic analysis also indicated that the AG genotypes in a Chinese population were significantly correlated with pulmonary tuberculosis (P < 0.01; OR = 0.57; 95% CI, 0.37-0.87).After adjustment for age and gender, G1186A sites were found to be dominant (P < 0.01; OR = 0.59; 95% CI, 0.40-0.87),over-dominant (P = 0.045; OR = 0.69; 95% CI, 0.47-0.99)and additive models (P = 0.041; OR = 0.76; 95% CI, 0.59-0.99) in association with pulmonary tuberculosis.But, no association was found between the other 5 SNPs (G1195A, T1212C, C1221G, C1303T and C1323T) and tuberculosis (P > 0.05).This study is the first to report that genetic variants in the MRC1 gene can be associated with pulmonary tuberculosis in a Chinese population, and may reduce the risk of infecting pulmonary tuberculosis.This also provides a new experimental basis to clarify the pathogenesis of pulmonary tuberculosis.

The immune system relies on pattern recognition receptors for the identification of invasion by exogenous pathogenic microorganisms. Nucleotide‐binding oligomerization domain2 is a member of the NLR family and is considered as non‐redundant recognition mechanism of Mycobacterium tuberculosis. The present study was conducted on the fourth exon of the NOD2 gene in 179 cases and 177 healthy controls using PCR sequencing, and found a synonymous mutation Arg587Arg which was located in the ultra‐coil encoding region (Winged Helix and Superhelical Domain) of the NOD2 protein. The synonymous mutation was CGT to CGG encoding the Arginine (OR: 2.06; CI: 1.18–3.60). There was a significant difference between tuberculosis patients and the healthy control group ( P <0.05), indicating the Arg587Arg site susceptibility to pulmonary tuberculosis. By focusing on the Pro268Ser, Arg708His and Aal725Val locus in the NOD2 gene, we found that the probability of this series was very low in a Chinese Han population and there was no significant difference ( P =0.267). We concluded that the single nucleotide polymorphism Arg587Arg in the NOD2 gene was significantly associated with tuberculosis in the Chinese population that provided new data for the world tuberculosis susceptibility research.