OBJECTIVE To investigate the influence of CYP2C19 gene polymorphism on platelet function and inflammatory cytokines in elderly patients with ischemic stroke， and to analyze potential factors associated with poor prognosis. METHODS A retrospective study was conducted on elderly patients with ischemic stroke admitted to our hospital from June 2024 to June 2025， wh o underwent CYP2C19 genotype testing and received antiplatelet therapy with clopidogrel. The levels of platelet function indicators and inflammatory cytokines before and after treatment were compared among patients with different metabolic phenotypes. Based on the prognosis at 6 months post-treatment， patients were divided into poor prognosis group and good prognosis group. Univariate analysis was performed on general data， metabolic phenotype， the levels of platelet function indicators and inflammatory cytokines. Variables with P ＜0.05 and the levels of inflammatory cytokines before treatment were included in a multivariate Logistic regression analysis to identify independent risk factors for poor prognosis. Multiple linear regression was used to further analyze the relationship between metabolic phenotypes and inflammatory cytokines. RESULTS A total of 448 elderly patients with ischemic stroke were included； among them， 162 cases were normal metabolic phenotype， 218 were intermediate metabolic phenotype， and 68 were poor metabolic phenotype. No rapid or ultrarapid metabolic phenotypes were observed. After treatment， platelet aggregation rate， the levels of P-selectin and platelet activated complex-1 （PAC-1）， high-sensitivity C-reactive Protein （hs-CRP）， interleukin-1β （IL-1β）， IL-6 and tumor necrosis factor-α （TNF-α） in the normal metabolic phenotype group， intermediate metabolic phenotype group， and poor metabolic phenotype group （except for platelet aggregation rate， and the levels of P-selectin and PAC-1 in the poor metabolic phenotype group） were significantly lower than those before treatment in the same group. Moreover， the above indicators in the normal metabolic phenotype group were significantly lower than those in the intermediate and poor metabolic phenotype groups at the corresponding time， and the levels of platelet function indicators in the intermediate metabolic phenotype group were significantly lower than those in the poor metabol ic phenotype group at the corresponding time （ P ＜0.05）. Univariate and multivariate Logistic regression analyses showed that combined with hypertension， combined with diabetes mellitus， and intermediate or poor metabolic genotypes were independent risk factors for poor prognosis in elderly patients with ischemic stroke （ P ＜0.05）. Multiple linear regression analysis showed that serum levels of hs-CRP， IL-1β， IL-6 and TNF-α before treatment were significantly higher in patients with intermediate and poor metabolic genotypes compared to those with normal metabolic genotype （ P ＜0.05）， with a greater magnitude of increase in inflammatory cytokines observed in the patients with poor metabolic genotype. CONCLUSIONS The elderly ischemic stroke patients with CYP2C19 intermediate and poor metabolic genotypes have poor inhibition effect on platelet and higher levels of inflammatory cytokines than normal metabolic genotype； CYP2C19 gene polymorphism， and in combination with hypertension and diabetes， can be used as independent predictors of poor prognosis.

ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Tracheobronchial adenoid cystic carcinoma （TACC） is a low-grade malignant tumor originating from the airway mucosa. Despite its slow progression，it is characterized by high invasiveness，frequent recurrence，and a strong tendency for metastasis. Preclinical studies have shown that vascular-targeted therapy holds significant potential. However，an effective systemic treatment for TACC has not been established yet. This study explored TACC from the perspective of "Feiji" in traditional Chinese medicine （TCM） as the starting point. It deeply investigated the mechanisms of abnormal collaterals and tumor vascular recruitment and further elaborated on the theoretical connection between abnormal collaterals and tumor vascular recruitment. Firstly，collateral hyperactivity led to disordered and erratic pulmonary collaterals. Their abnormal structures were similar to the disorderly and tortuous nature of tumor （pseudo）angiogenesis. This resulted in imbalances in the functions of circulation，perfusion，and reverse injection of the pulmonary collaterals，and then led to unrestrained collateral dysfunction and the accumulation of pathogenic factors. Secondly，the remodeling of the extracellular matrix （ECM） and epithelial-mesenchymal transition （EMT） in TACC were critical processes in vascular co-option （VCO），representing the micro-level manifestation of the displacement of nutrient and defense. During this process，ECM remodeling made TACC cells more likely to hijack normal blood vessels，creating a complex vascular microenvironment conducive to tumor growth. In terms of treatment，this study proposed a TCM strategy of "regulating collaterals to expel pathogenic factors and nourishing collaterals to strengthen the healthy Qi"，and listed potential TCM. These were intended to regulate the Qi and blood in the collaterals，repair the functions of abnormal collaterals，and intervene in the vascular recruitment process of TACC. Future research should focus on improving the TCM clinical syndrome characteristics of TACC. Through modern molecular biology techniques，it is necessary to deeply analyze the micro-level pattern of vascular recruitment in TACC. This would enrich the understanding of the profound connection between abnormal collaterals and tumor vascular recruitment，providing empirical evidence for TCM-targeted therapies for vascular recruitment in TACC.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate whether olfactory mucosa mesenchymal stem cells(OM-MSCs)attenuate oxygen glucose deprivation and recovery(OGD/R)-induced ferroptosis in neurons through glutathione oxidase 4(GPX4).Methods The middle nasal tissue were collected from a patient with nasal polyps admitted in our hospital,and then OM-MSCs were isolated from the tissue,which were confirmed by morphological observation under light microscopy and phenotypic characterization through flow cytometry for surface markers,including CD34,CD45,CD73,CD90,CD105,and CD146.Mouse hippocampal neuronal cell line HT22 was randomly divided into control,Control,OGD/R,OGD/R+OM-MSCs,OGD/R+sh-NC,OGD/R+sh-GPX4 and OGD/R+sh-GPX4+OM-MSCs groups.After the cells were subjected to OGD/R modeling,the cells were subsequently co-cultured with OM-MSCs and/or knockdown of GPX4.Neuronal apoptosis was quantified by flow cytometry,while cell viability was assessed using CCK-8 assay.Biochemical markers associated with ferroptosis,including MDA,ROS,GSH,and Fe2? levels,were measured with corresponding reagent kits.The GPX4 expression at both mRNA and protein levels was determined through qPCR and Western blotting,respectively.Results The isolated and primarily cultured OM-MSCs showed typical characteristics of OM-MSCs in cell surface markers(negative expression of CD34 and CD45 but positive expression of CD73,CD90,CD105,and CD146 on cell surface)and morphology(adherent cells in a spindle-like shape).Significant differences were observed among the control,OGD/R,and OGD/R+OM-MSCs groups in terms of cell viability,MDA,ROS,GSH,Fe2+and GPX4(P<0.05).The OGD/R group showed notable decreases in cell activity and GSH(P<0.05),increases in MDA,ROS,and Fe2+(P<0.05),and down-regulation of GPX4 when compared with the control group(P<005).Co-culture with OM-MSCs enhanced cell activity and GSH(P<0.05),decreased MDA,ROS,and Fe2+(P<0.05),and up-regulated GPX4 as compared to the conditions in the OGD/R group(P<0.05).While,OGD/R+sh-GPX4 treament developed the decreases in cell viability,GSH,and GPX4 and the increases in MDA,ROS,and Fe2+as compared to the OGD/R+sh-NC group(P<0.05),however,all of these could be reversed by OM-MSCs.Conclusion OM-MSCs inhibit OGD/R-induced ferroptosis in HT22 cells by up-regulating GPX4.

Albendazole-glucan particles(ABZ-GPS)and abendazole(ABZ)were used to treat secondary alveolar echinococ-cosis in mice.The therapeutic effects of ABZ-GPS on alveolar echinococcosis in vivo were evaluated,and the feasibility of using glucan particles as anti-hydatid drug carriers was further verified.Mice with echinococcosis were randomly divided into an ABZ group,glucan nanoparticle(GP)group,ABZ-GPS group,and control group.After four courses of administration with a final concentration of 50 mg/mL,the therapeutic effects of ABZ-GPS were evaluated on the basis of imaging,histopathological changes,ultrastructure,and immunology.After ABZ-GPS and ABZ administration,clear liver lesion tissue necrosis and large numbers of infiltrating lymphocytes were observed.Significant differences in the average cyst wet weight(t=7.83,P＜0.05),were observed between the ABZ-GPS group and ABZ group.Imaging revealed that ABZ-GPs were targeted to liver tissue.Pa-thology and ultrastructure analyses demonstrated that the alveolar hydatid cells in the liver in the control group and GP group grew well,and the vesicles were large,filled with cystic fluid,and translucent or transparent;the cyst wall tension was high;no calcification was observed;the stratum corneum and germinal layer were clear;and more fertile capsules and different num-bers of protocephalospora were present in the liver.In the ABZ group,the capsular cavity collapsed,and showed partial necro-sis and lymphocyte infiltration.In the ABZ-GP group,the corneum and germinal layer of echinococcus vesicles were difficult to identify,and we observed bulbous necrosis,central calcification,fibrous tissue hyperplasia,inflammatory cell infiltration,coarser,shorter or absent microvilli of the germinal layer,nuclear shrinkage,dissolution or disappearance,clear expansion of cytoplasmic microtubules,and myelin-like or vacuole-like changes.Therefore,ABZ-GPs showed good targeting and killing ac-tivity in vivo in mice with secondary alveolar coccosis.

Objective:To investigate the preferences for professional risks insurance among healthcare professionals in Chinese tertiary hospitals,providing a reference for understanding core demands and formulating personalized insurance plans.Methods:A questionnaire survey was conducted among 187 healthcare professionals from 9 tertiary hospitals in Shandong Province using acombination of stratified and convenience sampling.Mixed Logit models and the joint utility method were employed for analysis of the overall sample and clinical/non-clinical subgroups.Results:The mixed Logit model revealed that the type of compensation,insurance platform,and insurance duration significantly influenced the insurance attribute preferences of healthcare professionals(P<0.05),with the type of compensation having the greatest impact(β=0.220).The joint utility analysis indicated that insurance duration was of the highest relative importance(39%),while the premium amount was of the least importance(4%).In subgroup analysis,for clinical professionals,the type of compensation and insurance duration significantly influenced insurance attribute preferences,with the type of compensation having the greatest impact(β=0.277),followed by insurance duration.For non-clinical professionals,the premium amount and insurance platform were significant factors,with the premium amount being the most influential.Conclusion:Efficiency is a common core consideration for healthcare professionals when choosing insurance preferences,while economic factors are not central to the considerations of clinical professionals.The influence and role of medical associations in mitigating occupational risks need to be enhanced.It is suggested that future insurance products should fully consider the differences in the scope of practice,target certain attributes for enhancement,and strengthen the influence of medical associations in ensuring professional risks.

Objective:To investigate the clinicopathological features including immunophenotype, molecular characteristics, differential diagnosis and prognosis of SMARCB1-deficient renal medullary carcinoma (RMC) without sickle cell trait.Methods:The clinicopathological data of 12 cases of SMARCB1-deficient RMC without sickle cell trait were collected from 7 domestic institutions during the period of 2015 to 2024. Their clinical characteristics, morphological features and immunohistochemical properties were observed and analyzed. High-throughput DNA-targeted next-generation sequencing was performed, and follow-up data were gathered along with relevant literature review.Results:Among the 12 patients, 5 were female and 7 were male. The patients age ranged from 27 to 84 years with a median age of 58.5 (46.0, 71.0) years. None of them had sickle cell disease or other hemoglobinopathies. Eight cases occurred in the left kidney and 4 cases were located in the right kidney. The average maximum diameter of the tumor was 6.1 (4.0,7.5) cm, with a range of 2.0 to 14.9 cm (the median maximum diameter 5.5 cm). Histologically, the tumors showed poorly differentiated adenocarcinoma, arranged in solid and tubular patterns. Papillary structure was noted in 5 cases, cribriform structure in 3 cases, rhabdoid differentiation in 3 cases, and sarcomatoid differentiation in 2 cases. Inflammatory desmoplastic stromal reaction was observed in 8 cases, among which stromal myxoid degeneration was seen in 6 cases. Tumor necrosis was apparent in 6 cases. The tumor cells had abundant eosinophilic or clear cytoplasm and prominent nucleoli. The nuclear grading was grade 3 or 4 according to the International Society of Urological Pathology (ISUP). Immunohistochemical staining showed that the tumor cells of all 12 cases expressed PAX8 and loss of SMARCB1/INI1 protein expression, and 5 of 10 cases expressed OCT3/4. Seven samples had valid archived paraffin tissues for high-throughput DNA-targeted next-generation sequencing. The results showed that all 7 cases had pathogenic mutations in the SMARCB1 gene. The mutation sites included exon5 c.595A>T (p.K199*), exon2 c.200_207del (p.S67*), exon2 p.G69VfsTer16, exon7 c.986G>T (p.S329I), exon7 c.886A>T (p.K296*), exon6 c.635T>A (p.L212*), exon5 c.577del (p.M193Wfs16), and exon6 c.784del (p.V262Sfs5). Follow-up data were obtained for 6 of 12 patients. Among them, 1 patient had lung and bone metastases, 1 patient had liver and bone metastases and 1 patient had multiple bone metastases at the time of diagnosis; 1 patient had bone metastases 5 months after surgery. One patient died of postoperative complications 10 days after surgery, 4 patients died of tumors (the survival time ranged from 4 to 8 months), and 1 patient had no recurrence or metastasis during the 8-month follow-up after surgery.Conclusions:SMARCB1-deficient RMC without sickle cell trait is a highly aggressive and poorly differentiated renal cell carcinoma. It has similar histomorphology, immunophenotype, molecular characteristics and prognosis to RMC, which further supports that it is a sporadic subtype of RMC related to sickle cell trait.

Objective:To investigate the relationship between Ig class switch recombination(CSR)and mismatch repair(MMR)protein,microsatellite phenotype in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue(MALT lymphoma).Methods:Forty cases of MALT lymphoma archived in the Department of Pathology,Jiading District Central Hospital,Shanghai University of Medicine & Health Sciences were selected as the observation group,and twenty cases of benign lymphoid tissue hyperplasia were as the control group.The expressions of IgG,IgM,IgD,and IgA in both groups were detected by immunohistochemical double staining,and MMR proteins including MLH1,MSH2,MSH6,and PMS2 in both groups were detected by immunohistochemistry.Multiplex fluorescence PCR capillary electrophoresis was used to detect microsatellite phenotype in tumor and adjacent tissues of the experimental group.Results:In the observation group,the proportions of single Ig heavy chain expression(mode Ⅰ),negative expression(mode Ⅱ),and multiple expression(mode Ⅲ)were 65％(26/40),27.5％(11/40),and 7.5％(3/40),respectively,while in the control group were 0(0/20),5％(1/20),and 95％(19/20).The proportion of Ig heavy chain expression mode Ⅰ+Ⅱ in the observation group was 92.5％,which was significantly higher than 5％in the control group(P＜0.0 1).In the observation group,partial deletion of MMR protein was observed in 3 cases(7.5％),including 2 cases of MSH6 deletion and 1 case of both MSH6 and PMS2 deletion.In the control group,there was 1 case(5％)with PMS2 deletion.There was no significant difference in the deletion rate of MMR protein between the two groups(P＞0.05).A total of 5 cases of microsatellite instability(MSI)were detected in the observation group,including 1 case of low-frequency MSI(MSI-L),4 cases of high-frequency MSI(MSI-H),and 2 cases of MSI-H with MSH6 deletion.When the loss expression of MSI-H or MMR protein was counted as a positive result,the MSI-H rate detected by PCR capillary electrophoresis was 10％(4/40),which was slightly higher than the MMR protein deletion rate detected by immunohistochemistry(7.5％,3/40),but there was no statistically significant difference between the two groups(P＞0.05).The MMR protein deletion rates among the Ig heavy chain protein expression mode Ⅰ,mode Ⅱ,and mode Ⅲ groups were 0(0/26),18.2％(2/11),and 33.3％(1/3),respectively.There was a statistically significant difference in the constituent ratios among the three groups(P＜0.05).The MMR protein deletion rates among the MSS,MSI-L,and MSI-H groups were 2.9％(1/35),0(0/1),and 50％(2/4),respectively.There was a statistically significant difference in the constituent ratios among the three groups(P＜0.05).MMR protein deficiency was positively correlated with Ig heavy chain expression pattern and MSI(r=0.41,P＜0.05;r=0.48,P＜0.05),but Ig heavy chain expression pattern was not correlated with MSI(r=0.02,P＞0.05).Conclusion:Ig heavy chain CSR detection is helpful for the differential diagnosis of MALT lymphoma.Low frequency MMR protein deletion and MSI-H phenotype exist in MALT lymphoma,which may be of certain value for the study of its occurrence,development and clinical treatment.