Background:Rhei Radix et Rhizoma has been traditionally used as a potent laxative for centuries due to its remarkable efficacy.Raw pieces of Rhei Radix et Rhizoma(RP)are known for their strong laxative effects,often accompanied by side effects,while steamed Rhei Radix et Rhizoma pieces(SP)possess a milder laxative effect and are widely used clinically.However,there is a lack of comprehensive evidence examining the mechanisms underlying SP's effectiveness,particularly from a bioavailability perspective.Objective:This study aimed to investigate the impact of the steaming process on the in vivo disposition of RP and SP through pharmacokinetics,tissue distribution,and excretion assays.Methods:An ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous quantitative analysis of prototype anthraquinones and their glucuronide metabolites.Pharmacokinetic,tissue distribution,and excre-tion assays were conducted in constipation rats following oral administration of RP and SP.Blood,tissue,urine,and fecal samples were collected and analyzed to compare the absorption,distribution,metabolism,and excretion profiles of anthraquinones,high-lighting differences in bioavailability and safety between RP and SP.Results:Compared with the RP group,the SP group showed significantly reduced area under the plasma concentration-time curve,mean residence time,and half-life time values for rhein-8-O-β-D-glucopyranoside,rhein,emodin,aloe-emodin,and their glucuronide metabolites.The clearance values were significantly increased in the SP group.These results demonstrate that SP led to lower exposure levels and higher elimination rates of these components compared with RP.Additionally,these compo-nents were primarily distributed in the large intestine,where they exerted their laxative effects.Glucuronide metabolites were mainly excreted through urination,while prototype components were excreted in both urine and feces.Notably,the cumulative excretion of aloe-emodin,emodin,rhein,and their glucuronide metabolites was significantly higher in both urine and feces after SP administra-tion,indicating that SP enhances the excretion of these components compared with RP.Conclusion:The findings suggest that SP reduced anthraquinone exposure levels while enhancing their excretion,demonstrating that the steaming process significantly promotes the elimination of key components.This study provides a comprehensive analysis of how steaming alters the in vivo disposition of Rhei Radix et Rhizoma,offering a scientific basis for the improved safety and clinical use of SP.These insights not only clarify the mechanistic differences between RP and SP but also contribute to a broader understanding of processing-induced modifications in Chinese medicines.This research paves the way for optimizing Chinese medicine processing techniques to enhance the safety and efficacy of herbal therapies.

OBJECTIVE: To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province. METHODS: A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Ethics Number: 2019 Medical Ethics Review No. 67). RESULTS: Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c.1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c.467G>A (p.Gly156Asp) and c.1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c.1297G>C (p.Ala433Pro) and c.1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. CONCLUSION The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c.1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.
Humans ; Amino Acid Metabolism, Inborn Errors/epidemiology* ; Glutaryl-CoA Dehydrogenase/chemistry* ; Infant, Newborn ; Female ; Neonatal Screening/methods* ; Male ; Brain Diseases, Metabolic/epidemiology* ; China/epidemiology* ; Retrospective Studies ; Mutation ; Genetic Variation ; Glutarates

Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.

BackgroundDementia seriously affects the quality of life and lifespan of elderly people， with Alzheimer's disease （AD） being the most common type of dementia. Previous studies have suggested that gout may reduce the risk of developing AD， but the causal relationship between the two still requires further research. ObjectiveTo investigate the potential causal relationship between gout and AD through a two-sample Mendelian randomization （MR） analysis， so as to provide references for the prevention and treatment of AD. MethodsData from Genome-Wide Association Studies （GWAS） extracted in 2024 were analyzed， using pooled data on gout （6 810 cases in the case group and 477 788 cases in the control group） published by UK Biobank in 2021 as the exposure variable， and data on AD （3 899 cases in the case group and 214 893 cases in the control group） published by FinnGen in the same year as the outcome variable. The inverse-variance weighted， MR-Egger regression， weighted median estimation， simple model and weighted model were used to analyze the potential causal relationship between gout and AD. Pleiotropic effects were assessed using MR-Egger regression. Heterogeneity assessment was conducted using Cochran's Q test. The leave-one-out analysis was carried out for sensitivity analysis. And a funnel plot was drawn to detect potential publication bias. ResultsThe inverse-variance weighted analysis demonstrated a negative causal relationship between gout and AD （OR=0.004， 95% CI： 0~0.700， P<0.05）. The plot resembled a symmetrical inversed funnel， indicating the absence of publication bias. No heterogeneity was detected by Cochran's Q test. The MR-Egger regression indicated no significant horizontal pleiotropy. Concerning the reverse directions， no significant associations between AD and gout were noted. ConclusionThere is a negative causal relationship between gout and AD， with gout potentially reducing the risk of developing AD. ［Funded by The Third Batch of Social Welfare and Basic Research Projects （Medical and Health） of Zhongshan City in 2022 （number， 2022B3017）］

OBJECTIVE: To observe the effects of acupuncture on podocyte autophagy and long non-coding RNA SOX2 overlapping transcript (LncRNA SOX2OT)/mammalian target of rapamycin C1 (mTORC1)/Unc-51-like kinase 1 (ULK1) pathway in rats with diabetic kidney disease (DKD), and to explore the mechanism by which acupuncture reduces urinary protein. METHODS: A total of 40 SPF-grade male Sprague-Dawley rats were randomly divided into a control group (n=10) and a modeling group (n=30). The DKD model was established by feeding a high-fat, high-sugar diet combined with intraperitoneal injection of streptozotocin (STZ) in the modeling group. Twenty rats with successful DKD model were randomly divided into a model group (n=10) and an acupuncture group (n=10). The acupuncture group received "spleen and stomach-regulating" acupuncture at bilateral "Zusanli" (ST36), "Fenglong" (ST40), "Yinlingquan" (SP9), and "Zhongwan" (CV12), 30 min per session, once daily, five times per week, for four weeks. The general condition, fasting blood glucose (FBG), 2-hour postprandial glucose (2hPG), serum creatinine (SCr), blood urea nitrogen (BUN), 24-hour urinary protein quantification, and urine albumin-to-creatinine ratio (UACR) were compared before and after the intervention. After intervention, urinary podocyte injury marker SPON2 was measured by ELISA. Podocyte autophagosomes and glomerular basement membrane ultrastructure in renal tissue were observed via transmission electron microscopy. Podocyte apoptosis was assessed by TUNEL staining. The protein expression of microtubule-associated protein 1 light chain 3Ⅱ (LC3-Ⅱ), mTORC1, ULK1, Beclin-1, and p62 in renal tissue was detected by Western blot. LncRNA SOX2OT expression in renal tissue was measured by real-time PCR. RESULTS: After the intervention, compared with the control group, the model group exhibited increased food and water intake, increased urine output, weight loss, and loose stools; compared with the model group, the food and water intake, urine volume, and loose stools were improved in the acupuncture group. Compared with the control group, FBG, 2hPG, SCr, BUN, 24-hour urinary protein quantification, UACR, and urinary SPON2 were all higher in the model group (P<0.01); compared with the model group, the FBG, 2hPG, SCr, BUN, 24-hour urinary protein quantification, UACR, and urinary SPON2 were all lower in the acupuncture group (P<0.01). Compared with the control group, the model group showed reduced podocyte autophagosomes and thickened glomerular basement membrane; compared with the model group, the acupuncture group had increased podocyte autophagosomes and less thickened basement membrane. Compared with the control group, the podocyte apoptosis index (AI) was higher in the model group (P<0.01); compared with the model group, the AI was lower in the acupuncture group (P<0.01). Compared with the control group, the expression of ULK1, Beclin-1, and LC3-Ⅱ proteins was lower, and the expression of mTORC1 and p62 proteins was higher in the model group (P<0.01). Compared with the model group, the expression of ULK1, Beclin-1, and LC3-Ⅱ proteins was higher, and the expression of mTORC1 and p62 proteins was lower in the acupuncture group (P<0.01). Compared with the control group, the LncRNA SOX2OT expression was lower in the model group (P<0.01). Compared with the model group, LncRNA SOX2OT expression was higher in the acupuncture group (P<0.01). CONCLUSION The "spleen and stomach-regulating" acupuncture method could improve renal function in DKD rats, reduce blood glucose and urinary protein excretion, alleviate podocyte injury, and enhance podocyte autophagy. The mechanism may be related to modulation of the renal LncRNA SOX2OT/mTORC1/ULK1 pathway.
Animals ; Podocytes/cytology* ; Diabetic Nephropathies/physiopathology* ; Rats, Sprague-Dawley ; Male ; Rats ; Mechanistic Target of Rapamycin Complex 1/genetics* ; Autophagy ; Acupuncture Therapy ; Autophagy-Related Protein-1 Homolog/genetics* ; RNA, Long Noncoding/metabolism* ; Humans ; Signal Transduction

Objective: To understand the prevalence of myopia among primary and secondary school students in minority areas of Yunnan Province, and to explore the influence of outdoor activities and short-distance use of eyes, so as to provide a basis for early myopia intervention. Methods: In October 2020, the survey was conducted among 1 782 primary and secondary school students in three cities of Yunnan through a multi stage random cluster sampling method. All subjects underwent a questionnaire survey and the visual acuity examination at baseline. The first follow-up was conducted in October 2021 to obtain 1 691 valid samples, and the second follow-up was conducted in May 2023 to obtain 1 367 valid samples. Factors associated with myopia among primary and secondary school students were explored by using generalized estimating equations. Results: The prevalence rates of myopia in 2020, 2021 and 2023 were 52.64%, 61.62% and 69.35%, respectively, showing an increasing trend ( χ 2 trend =91.77, P <0.05). The results of multivariate regression analysis on the generalized estimation equations showed that age at baseline ( OR =1.31), girls ( OR =1.76), Hani ethnicity ( OR =0.75), Bai ethnicity ( OR =0.69), parental myopia ( OR =1.97-2.29), parents often reducing children s exercise time for homework or tutoring ( OR =1.35), less than 1 time or 2-3 times of ball sports per week ( OR =1.27, 1.20 ), reading and writing in the classroom during the break ( OR =1.27), reading in direct sunlight occasionally ( OR =1.20), using only desk lamp for writing at home ( OR =0.71), more than 1 hours of short-distance eye use for a break once ( OR =1.23) were associated with myopia among primary and secondary school students ( P <0.05). Conclusions Outdoor activities and short-distance use of eye among primary and middle school students in minority areas in Yunnan province are suboptimal. Enhancing the related environmental and behavioral factors can effectively mitigate the occurrence and progression of myopia.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17％.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49％.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3％at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100％.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.

OBJECTIVE To investigate the time-effect relationship of ginger-partitioned moxibustion in treating fecal inconti-nence in patients with mild to moderate active Crohn's disease so as to optimize moxibustion duration and provide a basis for clinical application.METHODS A total of 128 patients with Crohn's disease complicated by fecal incontinence who met the inclusion crite-ria were selected as the study subjects.They were divided into a control group and three experimental groups(experimental group Ⅰ,Ⅱ,and Ⅲ)of 32 patients each using a stratified random method(with 1 dropout in experimental group Ⅰ).Patients in the control group received routine anti-tumor necrosis factor-α monoclonal antibody(adalimumab)treatment,while patients in the experimental groups received ginger moxibustion therapy in addition to the treatment provided to the control group.Among them,experimental groupⅠ received treatment for 20 minutes,experimental group Ⅱ for 40 minutes,and experimental group Ⅲ for 60 minutes.The course of treatment for all four groups was 3 months.Changes in TCM syndrome scores were compared before and after treatment in the four groups to assess clinical efficacy.The cleveland clinic incontinence score(CCIS)was used to assess the severity of fecal incontinence,the Crohn's disease activity index(CDAI)was used to assess the degree of disease activity,and the inflammatory bowel disease ques-tionnaire(IBDQ)was used to evaluate the quality of life.Anal pressure index and peripheral blood CRP and ESR levels were mea-sured,and the relationship between moxibustion time and effect was analyzed.RESULTS After 3 months of treatment,the total TCM syndrome scores of all four groups improved to varying degrees(P<0.05,P<0.01).The total scores of groups Ⅰ,Ⅱ,and Ⅲ were supe-rior to those of the control group(P<0.05,P<0.01),while group Ⅱ had the lowest total TCM syndrome score.Group Ⅱ had the high-est overall clinical effective rate,significantly better than both the control and group Ⅰ(P<0.05,P<0.01).CCIS scores,IBDQ scores and total scores,and peripheral blood ESR levels were significantly reduced in all four groups(P<0.01),with group Ⅱ having the low-est score,lower than both the control and group Ⅰ(P<0.05,P<0.01).CRP levels were significantly reduced in groups Ⅱ and Ⅲ(P<0.05,P<0.01),both lower than the control group(P<0.05,P<0.01),with group Ⅱ lower than group Ⅰ(P<0.01).Intestinal symptom scores in the IBDQ of groups Ⅱ and Ⅲ were significantly higher than those in the control group and group Ⅰ(P<0.05,P<0.01).The maximum resting pressure of the anal canal,rectal defecation threshold,and maximum tolerance capacity all increased significantly in the four groups(P<0.05,P<0.01),but there were no significant differences among the groups(P>0.05).During the treatment,two cases of mild skin redness occurred in group Ⅲ,which resolved after treatment,with no serious adverse reactions.CONCLUSION Ginger moxibustion in the treatment of Crohn's disease complicated by fecal incontinence exhibits a time-effect relationship,with 40 minutes as the optimal duration.It can effectively improve symptoms,control inflammation,enhance quality of life,and has good safety.