ObjectiveTo observe the effects of Dihuang Yinzi （DY） on motor dysfunction in rats with advanced Parkinson's disease （PD） and to investigate the mechanisms by which DY improves advanced PD symptoms through the "gut microbiota-short-chain fatty acids （SCFAs）-inflammation-neuroprotection pathway". MethodsAn advanced PD rat model was induced by rotenone. Rats were divided into a normal group， model group， positive drug group （levodopa， 50 mg·kg^-1）， and DY low-， medium-， and high-dose groups （5.2， 10.4， 20.8 g·kg^-1）. After 7 days of administration， motor function was evaluated using the open-field， pole-climbing， and inclined plate tests. Hematoxylin-eosin （HE） staining was used to observe pathological changes in the substantia nigra and colon， and immunohistochemistry was performed to detect α-Synuclein （α-Syn） and tyrosine hydroxylase （TH） expression in the substantia nigra. Enzyme-linked immunosorbent assay （ELISA） was used to measure levels of dopamine （DA）， 5-hydroxytryptamine （5-HT）， 3，4-dihydroxyphenylacetic acid （DOPAC）， Levodopa， homovanillic acid （HVA）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）. Western blot analysis was used to detect the expression of zonula occludens-1 （ZO-1） and occludin. Gut microbiota diversity was analyzed by 16S rRNA sequencing， and gas chromatography （GC） was used to determine the content of SCFAs in colonic contents. ResultsCompared with the normal group， the model group showed significantly decreased movement speed and distance in the open-field test， prolonged pole-climbing time， and reduced retention angle on the inclined plate （P<0.01）， accompanied by increased α-Syn expression （P<0.01） and decreased TH expression （P<0.01） in the brain. Compared with the model group， all DY dose groups improved motor dysfunction in advanced PD rats to varying degrees （P<0.05， P<0.01） and alleviated pathological damage in the brain and colon. High-dose DY significantly reduced α-Syn aggregation in the substantia nigra （P<0.01） and increased TH expression （P<0.01）. ELISA and Western blot results showed that， compared with the normal group， the model group exhibited decreased levels of DA， 5-HT， DOPAC， Levodopa， and HVA in the striatum （P<0.01）， increased levels of TNF-α， IL-6， and IL-1β in the colon and striatum （P<0.01）， and significantly reduced expression of ZO-1 （P<0.05） and occludin in the colon （P<0.01）. Compared with the model group， all DY dose groups increased the levels of DA， 5-HT， DOPAC， Levodopa， and HVA in the striatum to varying degrees （P<0.05， P<0.01）. In the high-dose DY group， the levels of TNF-α， IL-6， and IL-1β in the colon and striatum were reduced （P<0.01）， while the expression of ZO-1 （P<0.05） and occludin in the intestine was increased. The 16S rRNA sequencing results indicated that the relative abundances of Actinobacteriota， Enterobacteriaceae， and Erysipelotrichaceae were increased in the model group， whereas the relative abundances of Bacteroidota， class Clostridia， Lachnospiraceae， and Akkermansia muciniphila were decreased. These changes were effectively reversed after high-dose DY intervention. GC analysis showed that the content of SCFAs in the colonic contents of rats in the model group was decreased （P<0.05， P<0.01）， while after high-dose DY intervention， the levels of acetate， propionate， isobutyrate， and butyrate were significantly increased （P<0.05， P<0.01）. ConclusionDY may exert therapeutic effects in advanced PD by regulating the gut microbiota-SCFAs-inflammation pathway.

OBJECTIVE: To assess the association of microribonucleic acid (miRNA) gene polymorphisms with the risk and clinicopathological characteristics of Crohn's disease (CD) and the influence of miRNA gene variants on the response to ustekinumab (UST) treatment among CD patients. METHODS: From January 2018 to February 2025, 312 patients diagnosed with CD and 527 gender- and age-matched normal controls were selected as the study subjects at the Department of Gastroenterology of the Second Affiliated Hospital of Wenzhou Medical University. Genotypes of miR-155 (rs767649), miR-21 (rs13137), miR-124 (rs531564) and miR-146a (rs57095329, rs2431697) were determined with multiplex polymerase chain reaction-ligase detection reaction (PCR-LDR) technique. The patients were divided into different subgroups according to the Montreal Classification Criteria for CD. Harvey-Bradshaw index (HBI) and simplified endoscopic score for CD were respectively applied to assess the clinical and endoscopic disease activity of CD. Unconditional logistic regression model was employed to analyze the distribution of miRNA gene polymorphisms between the two groups, as well as their influence on the clinicopathological characteristics of CD patients. Among them, 185 CD patients received first-line UST treatment, with the first sufficient dose of UST (6 mg/kg) administered intravenously. Based on the changes in HBI at week 8, the response of patients to UST treatment was evaluated. Unconditional logistic regression model was employed to analyze the distribution of miRNA gene polymorphisms between clinically responsive group (the decline of HBI ≥ 3 scores compared to week 0) and non-responsive group. All of the P values were adjusted by Bonferroni correction. This study has been approved by the Medical Ethics Committee of the Second Affiliated Hospital of Wenzhou Medical University (Ethics No.: 2025-K-12-01). RESULTS: No significant difference was found in the distribution of miRNA gene polymorphisms between the two groups (all P > 0.05). The variant genotype (TC+CC) of rs2431697 was more common among patients with terminal ileal-type and ileocolic-type CD than those with the colonic-type CD (OR = 4.98, 95%CI: 1.49~16.68, P = 0.009, adjusted P = 0.045). However, the opposite conclusion was drawn for the homozygous variant genotype (TT) of rs13137 and variant genotype (GC+CC) of rs531564 (OR = 0.37, 95%CI: 0.18~0.76, P = 0.007, adjusted P = 0.035; OR = 0.36, 95%CI: 0.18~0.73, P = 0.004, adjusted P = 0.020). Compared to patients with non-stricturing and penetrating CD, the variant genotype (AG+GG) and variant allele (G) of rs57095329 were more common in those with stricturing and penetrating CD (OR = 4.06, 95%CI: 2.46~6.71, P < 0.001, adjusted P < 0.005; OR = 3.12, 95%CI: 2.06~4.73, P < 0.001, adjusted P < 0.005). However, the frequencies of variant genotype (AT+TT) and variant allele (T) of rs13137 were lower among patients with stricturing and penetrating CD than in those without (OR = 0.25, 95%CI: 0.15~0.41, P < 0.001, adjusted P < 0.005; OR = 0.45, 95%CI: 0.33~0.63, P < 0.001, adjusted P < 0.005). Additionally, the variant genotype (AG+GG) and variant allele (G) of rs57095329 were more common among those with moderately to severely endoscopic activity than those with mildly endoscopic activity (OR = 2.01, 95%CI: 1.19~3.42, P = 0.009, adjusted P = 0.045; OR = 2.04, 95%CI: 1.28~3.25, P = 0.003, adjusted P = 0.015). In total 117 cases had shown clinical response by week 8, while 68 cases showed no response. Compared with t he clinically non-responsive group, the variant genotype (TC+CC) and variant allele (C) of rs2431697 were more common in the clinically responsive group (OR = 3.86, 95%CI: 1.80~8.32, P = 0.001, adjusted P = 0.005; OR = 2.60, 95%CI: 1.34~5.06, P = 0.005, adjusted P = 0.025). However, the variant genotype (TA+AA) of rs767649 was less frequent in the clinically responsive group than the non-responsive group (OR = 0.40, 95%CI: 0.21~0.74, P = 0.004, adjusted P = 0.020). The same conclusion was drawn for the variant genotype (AT+TT) and variant allele (T) of rs13137 when the clinically responsive group was compared with the non-responsive group (OR = 0.30, 95%CI: 0.14~0.63, P = 0.002, adjusted P = 0.010; OR = 0.54, 95%CI: 0.35~0.82, P = 0.005, adjusted P = 0.025). CONCLUSION Genetic polymorphisms of miRNAs are not associated with the risk of developing CD. The miR-146a (rs57095329) variant may increase the endoscopic activity of CD and the risk for stenosis or penetration. However, the miR-146a (rs2431697) variant may increase the risk of ileal involvement. The miR-21 (rs13137) variant may reduce the risk of ileal involvement and the risk of stenosis or penetration. The miR-124 (rs531564) variant may reduce the risk of ileal involvement. Among patients receiving UST treatment, the miR-146a (rs2431697) variant may increase the clinical response by week 8. However, both the miR-155 (rs767649) and miR-21 (rs13137) variants may decrease the clinical response by week 8.
Humans ; MicroRNAs/genetics* ; Crohn Disease/pathology* ; Male ; Female ; Adult ; Polymorphism, Single Nucleotide ; Middle Aged ; Asian People/genetics* ; Genetic Predisposition to Disease ; Genotype ; Young Adult ; Case-Control Studies ; Adolescent ; East Asian People

Objective To assess the risk of human Spirometra mansoni infections and investigate the knowledge, attitude and practice (KAP) towards sparganosis mansoni among residents in Henan Province, so as to provide insights into formulation of the sparganosis mansoni control measures. Methods Qinling Village in Fugou County of Zhoukou City, Bali Village in Yancheng District of Luohe City, Duzhai Village in Puyang County of Puyang City and Doushan Village in Luoshan County of Xinyang City were sampled as survey sites in Henan Province from July to August 2023, and more than 40 frogs were sampled from ponds or streams in each survey site for detection of Sparganum mansoni infections. At least 150 residents were sampled using a cluster sampling method from each survey site, and the sero-prevalence of anti-S. mansoni IgG antibody was estimated. In addition, a questionnaire survey was conducted on the KAP towards sparganosis mansoni among participants, and the proportion of eligible KAP, rate of correct KAP and KAP scores were calculated. Results A total 229 frogs were collected from 4 survey sites in 2023, and the overall prevalence of S. mansoni infection was 4.37% (10/229) in frogs, with 7.75% (10/129) prevalence in wild frogs and 0 in farm-bred frogs. A questionnaire survey was performed among 649 residents sampled from 4 survey sites, and 649 serum samples were collected. The seroprevalence of anti-S.mansoni IgG antibody was 0.15% (1/649) and the overall proportion of eligible KAP was 23.73% (154/649) among participants. There were age- (χ² = 30.905, P = 0.000), educational level- (χ² = 41.011, P = 0.000), and occupation-specific proportions of eligible KAP among participants (χ² = 10.721, P = 0.005), and the proportion of eligible KAP decreased with age (χ² _trend = 22.717, P = 0.000) and increased with education levels (χ² _trend = 40.025, P = 0.000). The rates of correct KAP towards sparganosis mansoni were 40.81% (2 119/5 192), 96.66% (1 882/1 947) and 63.81% (3 727/5 841) (χ² = 1 913.731, P = 0.000) among residents, respectively. The rates of correct KAP towards sparganosis mansoni varied significantly among survey sites (χ² = 136.872, 42.347 and 255.157; all P values= 0.000, with the highest rate of correct knowledge (51.94%, 748/1 440) and practices (75.86%, 1 229/1 620) in Yancheng District of Luohe City and the highest rate of correct attitudes in Puyang County of Puyang City (99.11%, 446/450) (all P values< 0.05). Conclusions There is still a high transmission risk of sparganosis mansoni in Henan Province, and the KAP towards sparganosis mansoni is required to be improved among residents.

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective: To analyze the impact of maternal metal exposure during early pregnancy on the physical development of offspring at 1 and 3 years of age, so as to provide scientific evidence for reducing the adverse effects of heavy metals on their health. Methods: From 2024 to 2018, a total of 1 588 mother child pairs from the Jiangsu Birth Cohort (JBC) were included in this study. Multiple linear regression models, generalized estimating equations (GEE), and weighted quantile sum (WQS) regression models were used to assess the associations between 24 urinary metal mass concentrations (adjusted for specific gravity, SG) during early pregnancy and offspring growth outcomes, including length/height for age Z score(HAZ), weight for age Z score(WAZ), weight for length/height Z score(WHZ), and head circumference for age Z score(HCAZ) at 1 and 3 years of age. Results: After adjusting for confounders, GEE analysis revealed that each natural log unit increase in maternal urinary concentrations of vanadium, tin, cerium, lead, and uranium during early pregnancy was associated with an average reduction in HCAZ by 14.29%, 4.82%, 2.62 %, 5.04 %, and 8.33%, respectively, at 1 and 3 years of age (FDR- P <0.05). Multiple linear regression analysis revealed that increased urinary vanadium concentration was associated with reduced HAZ at 1 year of age, while increased urinary concentrations of vanadium, chromium, tin, antimony, and uranium were associated with reduced HCAZ at 1 year of age (FDR- P <0.05). In the WQS regression model, each unit increase in the WQS index was associated with a 22.64% reduction in HCAZ at 1 year of age, with tin (22.2%) contributing the highest weight, followed by uranium (16.2%), lead (11.5%), vanadium (10.0%), arsenic (6.5%), and chromium (5.0%). Conclusions Prenatal exposure to specific metals and their mixtures may significantly impact the physical development of offspring at 1 and 3 years of age, particularly head circumference. These findings highlight the need to enhance monitoring of maternal metal exposure during early pregnancy to reduce the potential health risks posed by environmental metal pollution to infants and young children.

Objective To summarize the clinical and genetic characteristics of children with sodium taurocholate co-transporting polypeptide(NTCP)deficiency.Methods Clinical data of children with NTCP deficiency diagnosed and treated at the First People's Hospital of Yunnan Province from July 2022 to March 2025 were retrospectively analyzed.Results A total of 14 children were included(6 males,8 females),all with normal growth and development.Reasons for initial consultation included elevated serum bile acids in 7 cases,jaundice in 4 cases,cholestatic hepatitis in 1 case,and one case each of pneumonia and cow's milk protein allergy.At the first visit,all patients had elevated serum total bile acids beyond the normal range,with a mean of 152.5 μmol/L.Elevated alanine aminotransferase was observed in 1 case,elevated aspartate aminotransferase in 2 cases,and elevated total bilirubin in 10 cases.Genetic sequencing revealed that all children carried the homozygous SLC10A1 variant c.800C>T(p.Ser267Phe),classified as likely pathogenic.Conclusions NTCP deficiency often lacks obvious clinical symptoms and signs.Some children present with transient hyperbilirubinemia,cholestasis,or other liver function abnormalities.Persistent isolated elevation of serum bile acids warrants suspicion for this disease.Biallelic pathogenic variants in SLC10A1 constitute the basis for definitive diagnosis.There is no specific treatment for this disease,and management is mainly symptomatic.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective:To understand the prevalence of psychoactive substance use and related factors in men who have unprotected sex with men in Zhejiang Province.Methods:Men who have unprotected sex with men were recruited by snowball sampling through men who have sex with men (MSM) social organization in Zhejiang to conduct a cross-sectional investigation from January 2022 to December 2023. The sample size was estimated to be 1 169 individuals. The information about their socio-demographic information, sexual behaviors, psychoactive substance use, and HIV testing were collected through on-site questionnaire survey. Logistic regression analysis model was used to analyze related factors about psychoactive substance use in this population.Results:A total of 1 914 men who have unprotected sex with men were included in the study, the average age of the study subjects was (31.43±10.46) years, and most of them were aged ≤35 years (70.8%, 1 356/1 914). Those with education level of high school or below accounted for 50.1% (960/1 914) and those who were not married accounted for 63.5% (1 216/1 914). Psychoactive substance use in the past 3 months was reported in 19.7% (377/1 914) of the subjects. Multivariate logistic regression analysis showed that the factors associated with psychoactive substance use in the past 3 months included age 26-35 years (a OR=1.65, 95% CI: 1.24-2.19), ≥2 sexual partners in the past 3 months (a OR=2.33, 95% CI: 1.82-2.97), STD diagnosed in the past 3 months (a OR=2.62, 95% CI: 1.45-4.74), and awareness of the HIV infection status of sexual partners (a OR=2.83, 95% CI: 2.12-3.78). Conclusions:The prevalence of psychoactive substance use in men who have unprotected sex with men was high in Zhejiang. It is necessary to strengthen the intervention in this population.

Objective To study how lipid bilayer fluidity modulates the interaction between β1 integrin and CD40L,as well as the formation of CD40L-mediated tumor cell contact interfaces.Methods Supported lipid bilayers(SLB)with different fluidities were prepared through adjusting the 1,2-dioleoyl-sn-glycero-3-[N-(5-amino-l-carboxypentyl)iminodiacetic acid]succinyl nickel salt(DGS-NTA)content.The functionalization of lipid bilayers was achieved by anchoring fluorescently labeled CD40L molecules onto the membrane surface.The contact interface formation of PC9 cells on the functionalized lipid bilayers was observed through confocal fluorescence imaging and fluorescence recovery after photobleaching(FRAP)experiments,and data of two dimensional(2D)reaction kinetics of β1 integrin and CD40L were extracted from Zhu-Golan plots.Results The diffusion coefficient of molecules in lipid bilayer was negatively correlated with DGS-NTA content.High fluidity of lipid bilayer promoted CD40L accumulation at cell contact interface and expanded the cell contact area.The 2D dissociation constants(2D Kd)of β1 integrin-CD40L complexes were approximately 13,31 and 65 molecules/μm2 for the three lipid bilayers with high,moderate and low fluidities,respectively.Conclusions High fluidity of lipid bilayers significantly facilitates diffusion and aggregation of CD40L to the cell contact interface,thus enhancing β1 integrin-CD40L interaction and the stability of cell contact interfaces.