Sennoside A (SA), a typical prodrug, exerts its laxative effect only after its transformation into rheinanthrone catalyzed by gut microbial hydrolases and reductases. Hydrolases have been identified, but reductases remain unknown. By linking a photoreactive group to the SA scaffold, we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling (ABPP). From lysates of an active strain, Bifidobacterium pseudocatenulatum (B. pseudocatenulatum), 397 proteins were enriched and subsequently identified using mass spectrometry (MS). Among these proteins, chromate reductase/nicotinamide adenine dinucleotide (NADH) phosphate (NADPH)-dependent flavin mononucleotide (FMN) reductase/oxygen-insensitive NADPH nitroreductase (nfrA) was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource (UniProt) database screening. We also determined that recombinant nfrA could reduce SA. Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.

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Objective:This study aims to construct a quality evaluation index system for specialized disease databases. Through systematic assessment and optimization, it seeks to comprehensively enhance the quality and standardization of specialized disease cohort data. This initiative will provide more precise and reliable data support for disease research, the development of innovative drugs and medical devices, as well as policy formulation.Methods:By conducting a thorough analysis of domestic and international literature and policies related to clinical research data quality evaluation systems, preliminary quality evaluation indicators for specialized disease databases were established. Utilizing the Delphi method in two rounds, a quality evaluation system for specialized disease databases was constructed. The Analytic Hierarchy Process (AHP) and YAAHP 7.5 software were then employed to calculate the relative weights of indicators at various levels and their composite weights.Results:The two rounds of expert consultation achieved a 100.00% valid response rate, with an expert authority coefficient of 0.81 in both rounds. In the second round, the Kendall′s coordination coefficients for the first-level and second-level indicators reached 0.311 and 0.218, respectively ( P<0.05), indicating a good level of consensus among experts. The final specialized disease database quality evaluation system consists of 3 first-level indicators, 10 second-level indicators, and 32 third-level indicators. The first-level indicators include database construction, data quality, and cohort development, with weight coefficients of 31.82%, 41.49%, and 26.69%, respectively. The scientific validity of the indicator system was confirmed through reliability and validity analyses. When applied to assessing 58 specialized disease database projects from 36 medical institutions in a certain city, the results showed significant improvements in scores for database construction, data quality, and cohort development, with the most notable improvement observed in database construction. Conclusions:This study successfully developed a scientific, practical, and rationally weighted quality evaluation system for specialized disease databases, demonstrating high expert consensus and broad applicability.Validation studies have shown that this system effectively enhances the standardization and data quality of databases, providing robust technical support and assurance for specialized disease research and data resource sharing.

Sennoside A(SA),a typical prodrug,exerts its laxative effect only after its transformation into rhei-nanthrone catalyzed by gut microbial hydrolases and reductases.Hydrolases have been identified,but reductases remain unknown.By linking a photoreactive group to the SA scaffold,we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling(ABPP).From lysates of an active strain,Bifidobacterium pseudocatenulatum(B.pseu-docatenulatum),397 proteins were enriched and subsequently identified using mass spectrometry(MS).Among these proteins,chromate reductase/nicotinamide adenine dinucleotide(NADH)phosphate(NADPH)-dependent flavin mononucleotide(FMN)reductase/oxygen-insensitive NADPH nitroreductase(nfrA)was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource(UniProt)database screening.We also determined that recombinant nfrA could reduce SA.Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective: To analyze the trends, gender, and age differences in the incidence of lip and oral cavity cancer in Chinese population from 1990 to 2021 and predict future incidence trends, providing a scientific basis for disease prevention and public health policy. Methods: Incidence data of lip and oral cavity cancer in Chinese population from the Global Burden of Disease (GBD) database from 1990 to 2021 were analyzed. The Joinpoint regression model was used to assess temporal trends, the age-period-cohort model was used to evaluate the independent effects of age, period, and cohort, and the Bayesian age-period-cohort model (BAPC) model was used to predict incidence trends from 2022 to 2044. Results: From 1990 to 2021, the age-standardized incidence rate of lip and oral cavity cancer in Chinese population increased from 2.39/100 000 to 3.76/100 000, and the crude incidence rate rose from 1.71/100 000 to 4.85/100 000. The incidence rate in males was higher and increased more rapidly than in females. Higher incidence rates were prevalent among older populations, a rapid increase in incidence rates occurred during 2003 to 2012, and earlier birth cohorts showed overall higher risks. BAPC predictions indicated a continued rise in incidence from 2022 to 2044. During this period, male incidence stabilized while female incidence increased at a relatively faster rate. Conclusion The incidence of lip and oral cavity cancer in Chinese population has revealed a continuous upward trend, particularly among males and older populations. Future prevention strategies should focus on these high-risk populations.

OBJECTIVE: To investigate the effect of relaxing needling at the contracted sites of meridian-muscle regions in the patients with post-stroke shoulder-hand syndrome (SHS) at acute stage. METHODS: Eighty patients with post-stroke SHS at acute stage were randomized into an observation group (40 cases, 1 case dropped out) and a control group (40 cases, 1 case was eliminated). In the control group, the routine medication, basic rehabilitation training, and hyperbaric oxygen therapy were administered. In the observation group, besides the treatment as the control group, relaxing needling was delivered at the contracted sites of meridian-muscle regions. These contracted sites were distributed along three yin meridians of hand and three yang meridians of hand on the affected upper limbs. The intervention was given once daily, 5 times a week and for 4 weeks. Before and after treatment, the scores of visual analogue scale (VAS) for pain, edema degree, modified Barthel index (MBI), and Fugl-Meyer assessment (FMA) for motor function, and the integrated electromyography (iEMG) of surface electromyogram (sEMG) were observed in the two groups. The curative effect was evaluated after treatment and in follow-up of 2 months after treatment in the two groups. RESULTS: After treatment, VAS scores and the scores of edema degree were reduced when compared with those before treatment in the two groups (P<0.05), and the scores in the observation group were lower than those in the control group (P<0.05). MBI and FMA scores increased after treatment compared with those before treatment in the two groups (P<0.05), and the scores in the observation group were higher than those in the control group (P<0.05) after treatment. The iEMG values of the biceps brachii, triceps brachii, and wrist extensors were elevated after treatment in comparison with those before treatment (P<0.05) in the two groups, and the values in the observation group were larger than those in the control group after treatment (P<0.05). The total clinical effective rate in the observation group was 92.3% (36/39), which was better than that of the control group (74.4%, 29/39, P<0.05) after treatment; and that of the observation group was 97.4% (38/39), which was better than 82.1% (32/39) in the control group (P<0.05) in follow-up. CONCLUSION Relaxing needling at the contracted sites of meridian-muscle regions in treatment of post-stroke SHS at acute stage can attenuate the symptoms such as upper limb pain, swelling and spasm, improve motor function and the activity of daily living of patients.
Humans ; Male ; Female ; Middle Aged ; Acupuncture Therapy ; Aged ; Meridians ; Stroke/complications* ; Reflex Sympathetic Dystrophy/etiology* ; Adult ; Acupuncture Points

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective:To observe the short-term and medium-term clinical effects of electroacupuncture(EA)on patients with lumbar disc herniation(LDH)and to explore the cerebral effects based on resting-state functional magnet-ic resonance(rs-fMRI).Method:Thirty patients with LDH received EA at bilateral L3—S1 jiaji(EX-B2)and Dachangshu(BL25)points in continuous-wave mode at 20Hz(intensity adjusted to patient tolerance),20 minutes per session,every other day for ten sessions.Thirty-three age-and sex-matched healthy volunteers served as controls.All patients underwent rs-fMRI scans before treatment;The LDH group was rescanned one month after completion of EA.The modified Oswestry disability index(ODI),mental health summary(MCS)and physical health summary(PCS)of the short form health survey(SF-36)were assessed in LDH group before treatment and one,three,and six months after treatment.Voxel-wise regional homogeneity(ReHo)and degree centrality(DC)in brain areas were computed to compare between the two groups at baseline and pre-and post-treatment in LDH group.Result:After EA,LDH patients experienced significant reductions in ODI scores at one,three,and six months compared with baseline(P<0.05).PCS score continued to significantly improve at 3 months and 1 month(P<0.05),and the efficacy was the best at 3 months.There was a downward trend in 6 months after treatment,but still remained above baseline(P=0.072).The MCS score also rose at one and three months(P<0.05)but declined by six months.Compared with the control group,LDH patients exhibited increased ReHo in the left anterior cingulate gyrus,elevated DC in bilateral thalami,and decreased DC in bilateral postcentral gyri.After EA treatment,the LDH group showed increased ReHo in bilateral precuneus and the right middle frontal gyrus,as well as increased DC in the left postcentral gyrus.Conclusion:Electroacupuncture improves the short-term and medium-term clinical outcomes in LDH patients,with maximal benefit at three months.The role of electroacupuncture in improving pain and mental health is related to the regulation of pain matrix,default mode brain network,and emotional cognitive control network.