ObjectiveBased on the theory of "gut-prostate" axis， this study explored the effects and mechanisms of Zishen Tongguan formula and Cinnamomi Cortex in the formula in treating rats with chronic non-bacterial prostatitis（CNP） by detecting the levels of inflammatory factors， and the composition and structure of intestinal flora in CNP rats. MethodsEight out of 42 SD rats were randomly selected as the normal group， and the remaining rats were injected with carrageenan to prepare the CNP model. After successful modeling， 32 rats were randomly divided into the model group， Ningmitai capsule group（0.50 g·kg^-1）， Zishen Tongguan formula group（2.00 g·kg^-1）， and the Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma pair group（PCC-AR group， 2.00 g·kg^-1）， with 8 rats in each group. The administered groups were given the corresponding medicinal solution by gavage， and the normal and model groups were intragastrically administered with an equal volume of normal saline， once a day for 14 consecutive days. The prostate tissues of rats were collected and subjected to hematoxylin-eosin（HE） staining and Masson staining to observe the pathological changes of the tissues in each group. Enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of related inflammatory factors in rat serum， and 16S rDNA sequencing was used to analyze the abundance and diversity changes of gut microbiota before and after administration， and species difference analysis was performed. ResultsAll the administered groups could alleviate the inflammatory symptoms of CNP rats， increase the expression levels of anti-inflammatory factors and decrease the expression levels of pro-inflammatory factors， with the most sIgnificant effect observed in the Zishen Tongguan formula group. Compared with the normal group， the expression levels of interleukin（IL）-8， hypersensitive C-reactive protein（hs-CRP）， immunoglobulin（Ig）M， secretory IgA （sIgA）， and inducible nitric oxide synthase（iNOS） were sIgnificantly increased in the model group（P<0.01）. Compared with the model group， the expression levels of the above inflammatory factors in all administered groups were significantly reduced（P<0.01）. When compared with the PCC-AR group， the Zishen Tongguan formula group showed a significant decrease in transforming growth factor（TGF）-β₁ expression level（P<0.05） and a significant increase in IgM expression level（P<0.01）. The results of gut microbiota analysis showed that， compared with the PCC-AR group， at the order level， the Zishen Tongguan formula group significantly reduced the relative abundance of conditional pathogens such as Bacteroidales， Acidaminococcales， Rhodospirillales， Clostridiales， and Elusimicrobiales（P<0.01）. And at the genus level， the Zishen Tongguan formula group significantly decreased the relative abundance of pathogenic microbiota such as Lachnospira and Bacteroides（P<0.01） and significantly increased the relative abundances of beneficial microbiota such as Ruminococcus and Lactobacillus（P<0.01）. ConclusionZishen Tongguan formula can reduce the level of harmful intestinal bacteria， increase the level of beneficial intestinal bacteria， down-regulate the expression of serum inflammatory factors， and the small amount of Cinnamomi Cortex in the formula may play a key role in the treatment of CNP with this formula.

ObjectiveBased on the theory of "gut-prostate" axis， this study explored the effects and mechanisms of Zishen Tongguan formula and Cinnamomi Cortex in the formula in treating rats with chronic non-bacterial prostatitis（CNP） by detecting the levels of inflammatory factors， and the composition and structure of intestinal flora in CNP rats. MethodsEight out of 42 SD rats were randomly selected as the normal group， and the remaining rats were injected with carrageenan to prepare the CNP model. After successful modeling， 32 rats were randomly divided into the model group， Ningmitai capsule group（0.50 g·kg^-1）， Zishen Tongguan formula group（2.00 g·kg^-1）， and the Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma pair group（PCC-AR group， 2.00 g·kg^-1）， with 8 rats in each group. The administered groups were given the corresponding medicinal solution by gavage， and the normal and model groups were intragastrically administered with an equal volume of normal saline， once a day for 14 consecutive days. The prostate tissues of rats were collected and subjected to hematoxylin-eosin（HE） staining and Masson staining to observe the pathological changes of the tissues in each group. Enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of related inflammatory factors in rat serum， and 16S rDNA sequencing was used to analyze the abundance and diversity changes of gut microbiota before and after administration， and species difference analysis was performed. ResultsAll the administered groups could alleviate the inflammatory symptoms of CNP rats， increase the expression levels of anti-inflammatory factors and decrease the expression levels of pro-inflammatory factors， with the most sIgnificant effect observed in the Zishen Tongguan formula group. Compared with the normal group， the expression levels of interleukin（IL）-8， hypersensitive C-reactive protein（hs-CRP）， immunoglobulin（Ig）M， secretory IgA （sIgA）， and inducible nitric oxide synthase（iNOS） were sIgnificantly increased in the model group（P<0.01）. Compared with the model group， the expression levels of the above inflammatory factors in all administered groups were significantly reduced（P<0.01）. When compared with the PCC-AR group， the Zishen Tongguan formula group showed a significant decrease in transforming growth factor（TGF）-β₁ expression level（P<0.05） and a significant increase in IgM expression level（P<0.01）. The results of gut microbiota analysis showed that， compared with the PCC-AR group， at the order level， the Zishen Tongguan formula group significantly reduced the relative abundance of conditional pathogens such as Bacteroidales， Acidaminococcales， Rhodospirillales， Clostridiales， and Elusimicrobiales（P<0.01）. And at the genus level， the Zishen Tongguan formula group significantly decreased the relative abundance of pathogenic microbiota such as Lachnospira and Bacteroides（P<0.01） and significantly increased the relative abundances of beneficial microbiota such as Ruminococcus and Lactobacillus（P<0.01）. ConclusionZishen Tongguan formula can reduce the level of harmful intestinal bacteria， increase the level of beneficial intestinal bacteria， down-regulate the expression of serum inflammatory factors， and the small amount of Cinnamomi Cortex in the formula may play a key role in the treatment of CNP with this formula.

In the field of healthcare service,it is crucial to optimize medical innovation services by combining the preferences of health service providers and demanders(i.e.,stakeholders).The best-worst scaling(BWS)method is a recently developed stated preference method for assessing preferences with distinctive advantages.Nevertheless,there is a lack of a comprehensive introduction to stakeholder preference assessment using BWS,thus constraining its applications and promotion.This paper introduces the process of using BWS to assess service providers'preferences for the Shared Medical Appointment for diabetes(SMART),an integrated healthcare service of medicine and health management,in the hope of providing reference for researchers for promoting the use of BWS in implementation research.

The main pathological features of Parkinson disease(PD)include accumulation of α-synuclein and loss of dopaminergic neurons.PET imaging can be used to diagnose and monitor PD and explore its neural mechanisms through specific targeted imaging agents.The research progresses of PD related PET imaging agents were reviewed in this article.

Objective To investigate the effect of toripalimab combined with chemoradiotherapy in patients with cervical lymph node metastasis of nasopharyngeal carcinoma on immune function.Methods A prospective study was conducted in 160 patients with nasopharyngeal carcinoma accom-panied by cervical lymph node metastasis.Patients were divided into study group and control group using block randomization,with 80 patients in each group.The control group received a standard che-moradiotherapy regimen,while the study group received toripalimab combined with chemoradiothera-py.Both groups were treated for 3 courses.The clinical efficacy,levels of immune function indica-tors,levels of tumor markers[squamous cell carcinoma antigen(SCC-Ag),high-mobility group box 1(HMGB1),pentraxin 3(PTX3),and cytokeratin 19 fragment antigen 21-1(CYFRA21-1)],and the incidenceof adverse reactions were compared between the two groups.Results The objective re-sponse rates of the primary lesion and cervical lymph nodes in the study group were higher than those in the control group(P＜0.05).After treatment,the levels of CD3+,CD4+,and natural killer cells in the study group were higher than those before treatment and in the control group,while the lev-el of CD8+was lower than that before treatment and in the control group(P＜0.05).After treatment,the levels of HMGB1,PTX3,SCC-Ag and CYFRA21-1 in the study group were lower than those before treatment and in the control group,and the differences were statistically significant(P＜0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Toripalimab combined with chemoradiotherapy has a sig-nificant efficacy in treatment of cervical lymph node metastasis of nasopharyngeal carcinoma.It can enhance the immune function of patients,improve the levels of tumor markers,and has good safety.

OBJECTIVES: To reprogram human placental fibroblasts (HPFs) into chemically induced epithelioid-like cells (ciEP-Ls) using a combination of small-molecule compounds. METHODS: HPFs cultured under normoxic conditions were identified using immunofluorescence assay, PCR and chromosomal karyotyping. Under hypoxic conditions (37 ℃, 5% O₂), HPFs were cultured in a medium containing small-molecule compounds C6TSEDRVAJZ (CHIR99021, 616452, TTNPB, SAG, EPZ5676, DZNep, Ruxolitinib, VTP50469, Afuresertib, JNK-IN-8, and EZM0414), and the cell morphology was observed daily. The expression levels of epithelial cell markers in the induced cells were detected by immunofluorescence, Western blotting and PCR. Chromosomal karyotyping of the induced cells was performed and the induction efficiency was calculated. RESULTS: Before induction, HPFs showed positive expressions of fibroblast surface markers CD34 and vimentin and were negative for epithelial surface markers. PCR results showed high expressions of fibroblast-specific genes S100A4 and COL1A1 in HPFs with a normal human diploid karyotype. After one day of induction, the HPFs underwent morphological changes from a multinodular spindle shape to a round or polygonal shape, which was morphologically characteristic of ciEP-Ls. On day 4 of induction, the cells exhibited high expressions of the epithelial cell markers E-cadherin and Lin28A. RT-qPCR results also showed that the cells expressed the epithelial markers Smad3, GLi3, PAX8, WT1, KRT19, and KRT18 with significantly down-regulated expressions of all the fibroblast surface markers and a normal human diploid karyotype. The reprogramming efficiency of HPFs into ciEP-Ls ranged from (64.53±2.8)% to (68.10±3.6)%. CONCLUSIONS The small-molecule compound combination C6TSEDRVAJZ is capable of inducing HPFs into ciEP-Ls under hypoxic conditions with a high induction efficiency.
Humans ; Fibroblasts/drug effects* ; Pregnancy ; Female ; Cell Differentiation/drug effects* ; Pyrimidines/pharmacology* ; Placenta/cytology* ; Cells, Cultured ; Pyridines/pharmacology* ; Pyrazoles/pharmacology* ; Epithelial Cells/cytology*

Objective:To investigate the factors influencing the delayed onset of intrapartum fever following epidural labor analgesia and their impact on maternal and neonatal outcomes.Methods:Select parturients who experienced intrapartum fever following labor analgesia(T≥38.0℃,age≥18 years,singleton pregnancy,ASA classification Ⅱ)between January 1,2021,and December 31,2023.Group them based on the median time of intra-partum fever onset after labor analgesia:those with onset times less than the median were classified as the ear-ly-onset fever group,and those with onset times greater than the median were classified as the late-onset fever group.Using univariate and multivariate Logistic regression analysis to explore factors influencing the delay in in-trapartum fever onset and the pregnancy outcomes of the mothers and newborns in both groups.Results:A total of 253 parturients were included,and the time range of onset of intrapartum fever following epidural labor analgesi-a was 1.83-28.42 hours,with a median fever onset time of 8.00 hours.There were 126 cases in the early-onset group and 127 in the late-onset group.Multivariate Logistic regression analysis indicated that primiparous women,artificial membrane rupture,and neonatal birth weight were independent risk factors for delayed fever onset(OR＞1,P＜0.05),whereas the administration of oxytocin prior to labor analgesia was found to be a protective factor(OR＜1,P＜0.05).The late-onset group exhibited higher levels of white blood cells(WBC),C-reactive pro-tein,longer hospital stays,higher hospitalization costs,greater diagnosis rates of chorioamnionitis,higher NICU ad-mission rates,as well as a higher incidence of neonatal pneumonia,for newborns compared to the early-onset group(P＜0.05).Conclusions:Primiparous women,artificial membrane rupture,and higher neonatal birth weight may be associated with delayed onset of intrapartum fever,while oxytocin administration prior to labor analgesia may offer some protective benefit.The later the onset of intrapartum fever,the worse the clinical outcomes for both mother and infants.

An overview of the application of association rule mining(ARM)in real-world study(RWD)on drug safety to inform pharmacovigilance real-world data analysis.The applications of ARM in RWD of drug safety were divided into single drug/vaccine signal detection,combined medication risk mining,multidimensional risk factor analysis and adverse drug event occurrence characterization based on passive monitoring data;medication characterization pattern analysis,auxiliary epidemiological study design and risk mining of the whole dataset based on active monitoring data.In general,foreign scholars pay more attention to method rule setting,performance evaluation and application research,while domestic scholars pay more attention to multidimensional risk factor analysis,adverse drug event occurrence pattern,and clinical drug use characteristics research.With the accumulation of medical data and the continuous development of data mining technology,ARM may provide new ideas for RWD on drug safety.

Aim To explore the effects of apolipoprotein A Ⅰ(ApoA Ⅰ)and apolipoprotein A Ⅰ binding protein(AIBP)on THP-1-derived macrophage pyroptosis.Methods The lactate dehydrogenase(LDH)detection kit was used to evaluate cell membrane integrity,Hoechst33342/PI staining was used to observe cell membrane permeability,ELISA was used to detect the levels of inflammatory factors such as interleukin-1 β(IL-1β)and interleukin-18(IL-18),Western blot was used to detect the expression of pyroptosis-related protein nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3(NLRP3),gasdermin D(GSDMD),cleaved Caspase-1,IL-1β and IL-18.Results Oxidized low density lipoprotein(ox-LDL)upregulated the expression of NLRP3,GSDMD-N,cleaved Caspase-1,IL-1β and IL-18 in THP-1-derived macrophages in a concentration-dependent manner,and promoted the release of IL-1β,IL-18 and LDH(P＜0.05 or P＜0.01),indicating that ox-LDL induced pyroptosis in THP-1-derived macrophages in a concentration-dependent manner.Co-treatment of macrophages with ApoA Ⅰ and AIBP significantly downregulated the ex-pression of NLRP3,GSDMD-N,cleaved Caspase-1,IL-1β and IL-18,reduced the release of IL-1 β,IL-18 and LDH,and inhibited ox-LDL induced pyroptosis(P＜0.05 or P＜0.01).After ATP-binding cassette transporter A1(ABCA1)siRNA transfection,co-treatment with ApoA Ⅰ and AIBP had no significant effect on the expression of pyroptosis-related proteins and secretion of inflammatory factors(P＞0.05).Co-treatment of macrophages with ApoA Ⅰ and AIBP significantly re-duced the expression of purinergic 2X7R receptor(P2X7R)on the cell membrane,inhibited P2X7R mediated protein ki-nase R(PKR)phosphorylation and NLRP3 inflammasome assembly(P＜0.05 or P＜0.01).After P2X7R siRNA trans-fection,co-treatment with ApoA Ⅰ and AIBP had no significant effect on the expression of pyroptosis-related proteins and secretion of inflammatory factors(P＞0.05).Conclusion ApoA Ⅰ and AIBP reduce the expression of P2X7R on the cell membrane through ABCA1,inhibiting P2X7R/PKR/NLRP3 mediated macrophage pyroptosis.

Objective::To examine the impact of hypertensive disorders of pregnancy (HDP) on offspring metabolomics.Methods::We searched five databases: PubMed, Ovid Embase, MEDLINE, Web of Science, and China National Knowledge Infrastructure, and included studies that reported metabolomics among human offspring born to HDP-complicated pregnancies.Results::Database search yielded 4054 articles, and after full-text screening, ten observational studies met inclusion criteria. Half of the studies had a sample size of less than 100 and were all observational studies in preeclampsia (PE) and gestational hypertension.Neonates were the most focused group in all included studies. Offspring born to HDP-complicated pregnancies exhibited statistically significant variations in blood metabolomics compared to their counterparts, characterized by amino acids, lipids, carnitine, and others (e.g., 1α,25-(OH) 2-D). Most studies reported a significant increase in differential metabolites of offspring born to HDP-complicated pregnancies. Four studies ( n = 1109) measured lipids-related metabolites, and all consistently showed that offspring born to PE-complicated pregnancies had significantly higher concentrations than non-PE exposed offspring. Conclusion::The existing evidence suggests an intergenerational effect of HDP on offspring metabolomics. Long-term follow-up studies are needed to advance the health effects of related adverse health outcomes and inform the prevention of offspring’s health.