Objective: To explore the association between the HLA antibody positivity rate in female blood donors and pregnancy history, number of pregnancies, interval from the last pregnancy to blood donation, and age, to identify associated variables using a univariate generalized additive model (GAM), and to further analyze the predictive role of characteristic variables for HLA antibody positivity using a random forest model. Methods: HLA antibody detection was performed on 391 female blood donors using the Luminex immunomagnetic bead method. The correlation between pregnancy-related factors and HLA antibodies was analyzed using the Chi-square test. Based on R software, a univariate GAM was first constructed to analyze the association types between characteristic variables and the HLA antibody positivity rate, followed by the construction of a random forest model to evaluate the predictive value of the variables. Results: Among the 391 female blood donors without a transfusion history, the overall HLA antibody positivity rate was 26.34%. The positivity rate in donors with a pregnancy history was significantly higher than that in those without (30.09% vs 9.72%, P<0.05), and HLA antibody positivity rate increased linearly with the number of pregnancies (P<0.05). In the univariate GAM, age and number of deliveries exhibited a non-linear association with the HLA antibody positivity rate (the positivity rate increased sharply between 25-35 years of age and stabilized after 3 deliveries). Besides, the interval from the last pregnancy to blood donation showed a linear association with the HLA antibody positivity rate, and the positivity rate decreased as the interval prolonged (P<0.05). In the random forest model, age (mean decrease gini=29.26) and interval from the last pregnancy to blood donation (mean decrease gini=22.02) were core predictive variables: age was more conducive to identifying positive samples, while the interval from the last pregnancy to blood donation was more helpful for excluding negative samples. The number of deliveries (mean decrease accuracy=16.98) made a significant contribution to predicting positive samples, whereas the number of abortions had no impact. The model had an AUC of 0.583 (95% CI: 0.593 8-0.770 2), indicating a certain predictive value. Conclusion: The associated variables identified by the univariate GAM model, including age, interval from the last pregnancy to blood donation, and number of deliveries, provide a basis for key variables in the random forest model. All three variables have predictive value for HLA antibody positivity, which can provide evidence-based support for personalized transfusion management and stratified screening of female blood donors in this region.

Objective To investigate the prevalence of thyroid nodules in the physical examination population in Mianyang region and analyze its association with metabolic syndrome. Methods A retrospective study was conducted on 9 978 individuals who underwent health examinations at our hospital from January 2024 to May 2025. Thyroid examinations were performed using color Doppler ultrasound to analyze the prevalence of thyroid nodules in this population. Clinical data of all subjects were collected, and logistic regression analysis was employed to assess the association between metabolic syndrome and the risk of thyroid nodule development. Results The prevalence of thyroid nodules in the physical examination population of Mianyang region was 17.98% (1 794/9 978). The logistic regression results showed that after adjusting for gender, age, BMI, occupation, consumption of non-iodized salt, staying up late, daily sleep duration, anxiety, and depression, metabolic syndrome (OR=6.593, 95% CI: 3.961-10.975) was associated with thyroid nodules (P<0.05). Conclusion The prevalence of thyroid nodules among the physical examination population in the Mianyang area is 17.98%, and metabolic syndrome remains associated with the risk of thyroid nodules after effectively controlling for confounding factors.

In March 2024, three male and two female specimens of the genus Lispe were intercepted on cargo ships inbound for Wan Zai Port under Gongbei Customs. Based on morphological characteristics and molecular analysis, the specimens were identified as Lispe pumila. In this study, we describe the morphological features, diagnostic characteristics, and geographical distribution of L. pumila, with the aim of providing a reference for the identification of this species when intercepted at ports.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

BackgroundSuicide and self-injury risk in patients with depression disorder is associated with pain symptoms， but the relationships between specific pain types and their severity and distinct self-injury/suicide risk phenotypes remain controversial. ObjectiveTo explore whether somatic pain can reflect different self-injury/suicide risk phenotypes， and to provide references for the clinical identification of suicide and self-injury risk in patients with depression. MethodsBased on data from the National Survey on Symptomatology of Depression （NSSD）， 3 275 patients who met the diagnostic criteria for major depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders， fourth edition， text revision （DSM-IV-TR） were recruited. According to previous suicidal behavior， suicidal ideation and self-injury behavior in the past two weeks， patients were divided into the no self-injury/suicide risk group， self-injury group， and high suicide-risk group. The occurrence of headache， muscle soreness， trunk pain， limb pain， and other pain symptoms was assessed using the structured symptom assessment instrument of the NSSD. With the no self-injury/suicide risk group as the reference， an ordinal Logistic regression model was used to analyze the associations between the risk groups and the occurrence frequency of pain， with demographic and clinical characteristics entered into the model as covariates for adjustment. ResultsA total of 3 211 patients （98.05%） were included in the analysis， including 1 329 cases （41.39%） in the no self-injury/suicide risk group， 415 cases （12.92%） in the self-injury group， and 1 467 cases （45.69%） in the high suicide-risk group. Compared with the no self-injury/suicide risk group， the occurrence frequencies of headache （OR=1.526， 95% CI： 1.221–1.894） and muscle soreness （OR=1.287， 95% CI： 1.034–1.597） were higher in the self-injury group， and the occurrence frequencies of headache （OR=0.583， 95% CI： 0.504–0.672）， muscle soreness （OR=0.682， 95% CI： 0.597–0.780）， trunk pain （OR=0.557， 95% CI： 0.475–0.634）， limb pain （OR=0.454， 95% CI： 0.384–0.522）， and other pain difficult to localize （OR=0.542， 95% CI： 0.472–0.631） were all lower in the high suicide-risk group. ConclusionPatients with depression disorder across different self-injury and suicide risk phenotypes exhibit distinct pain characteristics， and these differences may provide a reference for the clinical identification of suicide and self-injury risk in patients with depression disorder. ［Funded by The National Key Research and Development Program of China during the "13th Five-Year Plan" period （number， 2016YFC1307100）； Shanghai Key Clinical Specialties Construction Project］

Helicobacter pylori （H. pylori） infection is not only associated with gastrointestinal diseases， but also potentially links with neuropsychiatric disorders revealed by recent studies. Through a systematic review of the existing literature， this review summarizes epidemiological evidence for the association between H. pylori infection and diseases such as Parkinson′s disease （PD）， Alzheimer′s disease （AD）， multiple sclerosis （MS）， migraine， depression， and anxiety disorders， and further explores potential mechanisms by which it affects central nervous system function， including neural pathways mediated by the enteric nervous system and the vagus nerve， immune pathways mediated by inflammatory cytokines， and endocrine pathways mediated by gut microbial metabolites. Additionally， the current challenges facing H. pylori eradication therapy and the prospects for emerging adjuvant strategies such as probiotics and fecal microbiota transplantation are discussed. Finally， future research directions are outlined， emphasizing the need for prospective cohort studies based on standardized diagnostic methods and further investigation using animal models to elucidate the pathophysiological mechanisms， with the aim of providing new perspectives for the prevention， treatment， and early intervention of related neuropsychiatric disorders.

ObjectiveTo investigate the efficacy of Poge Jiuxin decoction （PGJXD） on fluid resuscitation in septic shock patients and its effects on vascular endothelial function based on clinical randomized controlled trials （RCTs） and network pharmacology， and to reveal its molecular mechanisms and signaling pathways through network pharmacology. MethodsSeventy-two septic shock patients were enrolled and randomly assigned to either the treatment group or the control group （36 cases each） through a random number table. Both groups received conventional Western medical treatment for sepsis. Additionally， the treatment group received PGJXD （100 mL， twice daily） for 3 consecutive days. The two groups were compared in terms of the Sequential Organ Failure Assessment （SOFA） score， Acute Physiology and Chronic Health Evaluation Ⅱ （APACHE Ⅱ） score， vascular endothelial function indicators ［endothelium-derived relaxing factor （EDRF）， nitric oxide （NO）， and 6-keto-prostaglandin F_1α （6-keto-PGF_1α）］， inflammation indicators ［tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， nuclear factor kappa-B （NF-κB）， and procalcitonin （PCT）］， perfusion indicators ［mean arterial pressure （MAP）， lactate （Lac）， and 72-hour lactate clearance rate （Lcr）］， fluid resuscitation target achievement time， vasopressor use duration， length of hospital stay， and 28-day mortality. Databases including TCMSP， HIT 2.0， and Uniprot were searched for active components of PGJXD and their targets. Gene targets for septic shock were obtained from GeneCards， OMIM， and DrugBank databases. Venny software was used to identify common targets between PGJXD and septic shock. Cytoscape software and the STRING database were utilized to construct a "drug-component-target-disease" network and a protein-protein interaction （PPI） network. Gene Ontology （GO） functional enrichment analysis， Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis， and molecular docking were performed to explore the molecular mechanisms and signaling pathways of PGJXD in treating septic shock. ResultsFive patients withdrew from the treatment group and seven from the control group. After treatment， both groups showed decreases （P<0.01） in APACHE Ⅱ score， SOFA score， EDRF， 6-keto-PGF_1α， TNF-α， IL-6， NF-κB， PCT， MAP， and Lac， and increases in NO （P<0.01）. The treatment group exhibited more significant decreases （P<0.05， P<0.01） in APACHE Ⅱ score， SOFA score， 6-keto-PGF_1α， TNF-α， IL-6， NF-κB， MAP， Lac， Lcr， fluid resuscitation target achievement time， and vasopressor use duration than the control group. Differences in EDRF， NO， PCT， length of hospital stay， and 28-day mortality were not statistically significant. No significant adverse reactions were observed in either group during treatment. Network pharmacology identified 189 components and 257 potential targets of PGJXD， and 136 common targets shared by PGJXD and septic shock. GO enrichment analysis primarily involved positive regulation of cell migration， response to peptide， response to inorganic substance， etc. KEGG enrichment analysis mainly implicated signaling pathways such as NF-κB， VEGF， and Relaxin. ConclusionPGJXD can significantly ameliorate the condition of septic shock patients and enhance the efficacy of fluid resuscitation. Its key mechanism may involve protecting vascular endothelial cells by regulating the TNF-α/NF-κB signaling pathway and reducing the inflammatory response.

Objective To preliminarily analyze the genotypic and phenotypic characteristics of glucose-6-phosphate dehydrogenase(G6PD)in blood donors and recipients in Dongguan region,as well as the impact of these characteristics on the efficacy of blood transfusion therapy.Methods A total of 351 pairs of blood sam-ples from donors and recipients were collected from the Tenth Affiliated Hospital of Southern Medical Uni-versity/Dongguan People's Hospital between May and November in 2023.These samples were tested for G6PD genotype,G6PD enzyme activity,erythrocyte osmotic fragility,and blood routine parameters.Addition-ally,hemoglobin levels before and after blood transfusion were collected from recipients for statistical analy-sis.Results The carrier rates of G6PD mutant genes among donors and recipients in Dongguan region were 6.84％and 5.83％,respectively.Six mutation sites were identified,with c.1388G＞A,c.1376G＞T,and c.95A＞G accounting for 84.09％of all mutations.A negative correlation was observed between G6PD activi-ty and blood storage duration in wild-type donors.The G6PD activity significantly decreased when blood from healthy donors was transfused into recipients through standard procedures.Recipients carrying c.1388G＞A,c.1376G＞T,c.95A＞G,c.871G＞A,c.1024C＞T mutation sites showed no statistically significant difference in hemoglobin increment after receiving blood from donors carrying c.1388G＞A,c.1376G＞T,c.95A＞G,c.871G＞A,c.1376G＞T/c.1360C＞T,or c.1388G＞A/c.95A＞G mutation sites.In the internal medicine re-strictive transfusion group,recipients who received blood with enzyme activity≥1300 U/L demonstrated a significantly greater increase in hemoglobin levels compared to those transfused with blood with enzyme activ-ity＜1 300 U/L(P=0.042).Conclusion The carrier rates of G6PD mutant genes among donors and recipi-ents in Dongguan region are both above 5.00％,indicating a relatively high carriage rate.The three primary mutation sites,c.1388G＞A,c.1376G＞T,and c.95A＞G,account for over 80.00％of all mutations.No ad-verse effects on treatment efficacy are observed in recipients carrying G6PD mutant genes after receiving blood from donors with G6PD mutant genes.However,in restrictive transfusion practices within internal medicine,recipients receiving blood with low G6PD enzyme activity demonstrate a reduced hemoglobin increase per unit compared to those receiving blood with normal G6PD enzyme activity.

Background and aims:Primary sclerosing cholangitis(PSC)is an autoimmune liver disease characterized by complex pathogenesis and limited available therapeutic options.The mechanisms underlying the development and progression of PSCs remain unclear.Liver X receptor beta(LXR-β)is recognized to modulate lipid metabolism and immune response,but its specific involvement in the PSC has not been elucidated.Here,we explored the role and mechanism of LXR-β in PSC induced by 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine(DDC).Methods:CRISPR-Cas9 technology was applied to generate Abcb4(coding MDR2,next named as Mdr2),Nr1h2(coding LXR-β,next named as Lxrβ),and Rag2(coding RAG2)knockout mice.DDC was used to induce PSC.Hematoxylin and eosin and Sirius red staining were used to assess the extent of hepatic injury and fibrosis.Flow cytometry was used to observe immune cell subsets.Results:We observed a declining trend in hepatic Lxrβ in the PSC model.Unexpectedly,Lxrβ knockout failed to modulate DDC-induced PSC pathogenesis.Concomitantly,assessment of the influence of Rag2 deficiency on PSC progression revealed the absence of aggravated or alleviated hepatic injury or fibrosis in the Rag2-/-DDC mice.However,Lxrβ depletion intensified DDC-induced PSC in the Rag2-/-mice,with more abundant infiltrative inflammatory cells and more severe liver fibrosis.Compared with Rag2-/-DDC mice,Lxrβ-/-Rag2-/-DDC mice had higher serum ALT and AST levels and mRNA expression of proinflammatory and profibrotic genes.Flow cytometry showed that LXR-β deficiency resulted in a diminished population of hepatic innate immune cells.Conclusion:This study indicated innate immune cell LXR-β deficiency can exacerbate hepatic injury and fibrosis in murine models of PSC suggesting that LXR-β may regulate the function of innate immunity in the fibrotic advancement of PSC.

Objective To investigate the mechanism by which Senegenin(SEN)alleviates microglial inflammatory response through the nuclear factor erythroid 2-related factor 2(Nrf2)/NOD-like receptor protein 3(NLRP3)pathway.Methods BV2 mouse microglia cells were randomly divided into control group,model group,SEN group and MCC950 group.Cells in control group were not treated,and cells in model group were added with 1 μg/ml lipopolysaccharide(LPS);Cells in SEN group were added with 1 μg/ml LPS+4 μmol/L SEN,and cells in MCC950 group were added with 1 μg/ml LPS+10 μmol/L MCC950 for 24 hours.CCK-8 method was used to detect the effect of different concentrations of SEN on the viability of BV2 cells.Griess method was used to determine the release amount of nitric oxide(NO)in the supernatant.Real-time fluorescent quantitative PCR was used to determine the mRNA expression levels of NLRP3,lymphocyte apoptosis-associated spect-like protein containing a CARD(ASC),caspase-1,interleukin(IL)-1β and IL-18 mRNA.Immunofluorescence staining was used to detect the expression levels of ASC,IL-1β,Nrf2 and heme oxygenase-1(HO-1).Western blotting was used to detect the expression levels of NLRP3,caspase-1,ASC,IL-1β,IL-18,Nrf2,HO-1,nuclear factor kappa B(NF-κB)and inducible nitric oxide synthase(iNOS).Results The results of CCK-8 method showed that there was no significant difference in the viability of BV2 cells treated with 2～20 μmol/L SEN compared with control group(P>0.05).Compared with control group,the viability of BV2 cells in model group decreased significantly(P<0.05).Compared with model group,the viability of BV2 cells in 4 μmol/L SEN group was significantly restored(P<0.05).Compared with control group,the results of Griess method showed that the release amount of NO in cells of model group increased significantly(P<0.05);the results of real-time PCR showed that the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA in cells of model group increased significantly(P<0.05);the results of Western blotting showed that the protein expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 proteins in cells of model group increased significantly(P<0.05),and the immunofluorescence staining results showed that the expression levels of iNOS and NF-κB protein in cells of model group increased,and the expression levels of Nrf2 and HO-1 decreased,with statistically significant differences(P<0.05).Compared with model group,the release amount of NO in cells of SEN group and MCC950 group decreased,and the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA and proteins decreased,with statistically significant differences(P<0.05);in the SEN group,the expression levels of iNOS and NF-κB decreased,and immunofluorescence staining showed that Nrf2 was translocated into the nucleus,and the expression levels of Nrf2 and HO-1 proteins increased significantly,with statistically significant differences(P<0.05).Conclusions SEN could alleviate the inflammatory response of mouse microglia cells induced by LPS and inhibit the activation and expression of NLRP3 inflammasome,with an effect comparable to that of the inflammasome inhibitor MCC950.The mechanism may be related to the regulation of the expression of upstream factors Nrf2 and HO-1.