epsis is a systemic inflammatory response syndrome triggered by infection， and its high mortality rate is closely associated with immune imbalance， particularly the imbalance in the differentiation of helper T cell （Th） cell subsets [Th1， Th2， Th17， regulatory T cell （Treg） ] . In recent years， traditional Chinese medicine （TCM）， with its characteristics of multi-component and multi-target actions， has demonstrated unique advantages in regulating Th cell differentiation and function， as well as correcting immune imbalances in sepsis， offering new perspectives for immunotherapy of sepsis. This review summarizes relevant studies on the regulation of Th cell differentiation for sepsis treatment by TCM monomers and active ingredients （such as Astragalus membranaceus ， Scutellaria baicalensis ， Coptis chinensis ， Rheum palmatum ， Ganoderma lucidum ， Ginkgo biloba ， and Cistanche deserticola ）， the alcohol extract of Dai Baijie， and TCM formulas and preparations categorized as blood-activating and stasis-removing， purgative and laxative， warming and tonifying yang， and tonifying qi and nourishing yin. The results indicate that these TCM monomers， active ingredients， extracts， formulas， and preparations can regulate the Th1/Th2 and Th17/Treg balance， target the differentiation balance of Th cell subsets， alleviate inflammatory responses， or improve immune suppression， thereby exerting therapeutic effects on sepsis.

Objective: To evaluate the efficacy and safety of ruxolitinib combined with low-dose hormone for patients with acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Thirty patients with aGVHD after allo-HSCT admitted to the Department of Hematology of the General Hospital of Western Theater Command from November 2021 to November 2024 were retrospectively analyzed. All patients were treated with low-dose hormone (methylprednisolone 0.3-1 mg kg -d ) combined with ruxolitinib 5-10 mg d . The efficacy and adverse reactions were observed during the follow-up period to analyze the survival outcomes of the patients. Results: A total of 30 patients with aGVHD after allo-HSCT were included in this study, consisting of 15 (50%) males and 15 (50%) females with a median age of 34 year-old (ranging from 14 to 62). Classification by disease type: there were 18 cases of acute myeloid leukemia, 4 cases of acute lymphoblastic leukemia, 4 cases of aplastic anemia, and 4 cases of myelodysplastic syndrome. Classification by aGVHD severity: there were 27 cases (90%) of Ⅱ-Ⅳ degree aGVHD and 11 cases (36.7%) of Ⅲ-Ⅳ degree aGVHD. Ruxolitinib in combination with low-dose glucocorticoid treatment yield responses in 28 (93.3%) patients, of which 27 (90%) achieved complete remission (CR), while 1 (3.3%) showed partial remission (PR). One patient (3.3%) had no response (NR), and 1 patient (3.3%) exhibited progressed disease (PD). Overall survival (OS) at 1 year of transplantation was 73.9% (95%CI 49.5% to 87.7%), progression-free survival (PFS) was 93.3% (95%CI 75.9% to 98.3%), non-relapse mortality (NRM) was 20.6% (95%CI 7.9% to 47.4%), and median survival time was 27.6 months. Conclusion: Ruxolitinib combined with low-dose hormones is safe and effective in the treatment of aGVHD after allo-HSCT.

Background and purpose:Modified radical mastectomy is an important approach for treating breast cancer,but the risk of postoperative incision infection rate is relatively high,which can seriously affect the treatment outcome and prognosis of these patients.This study aimed to investigate the etiological characteristics,related risk factors and changes of serum inflammatory factors such as procalcitonin(PCT),C reactive protein(CRP),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)in patients undergoing modified radical mastectomy.Methods:The clinical data of breast cancer patients admitted to the Third People's Hospital of Zhengzhou from February 2019 to February 2022 were analyzed retrospectively.The pathogenic bacteria distribution and related risk factors of postoperative incision infection and the changes of serum inflammatory factors such as PCT,CRP,TNF-α and IL-6 were explored.This study has been approved by the Medical Ethics Committee of the Third People's Hospital of Zhengzhou(No.:2025-04-014-K01)and acquired the informed consent.The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist was followed for this case control study.Results:A total of 128 patients were enrolled in this study.All patients underwent modified radical mastectomy were divided into infected group(n=22)and non-infected group(n=106)according to whether incision infection occurred after surgery.The incision infection rate after modified radical mastectomy was 17.19%(22/128).Twenty-six strains of pathogenic bacteria were isolated and cultured from 22 patients with postoperative incision infection.Among these,16 strains were Gram-positive,accounting for 61.54%(16/26),mainly staphylococcus aureus and enterococcus faecalis.There were 10 Gram-negative strains,accounting for 38.46%(10/26),mainly escherichia coli and pseudomonas aeruginosa.The influencing factors of incision infection after modified radical mastectomy included preoperative neoadjuvant chemotherapy,intraoperative blood loss≥300 mL,postoperative drainage volume≥800 mL,drainage time≥7 d,albumin＜35 g/L,and white blood cell count＜4×109/L(P＜0.05).Multivariate logistic regression analysis showed that preoperative neoadjuvant chemotherapy,blood loss≥300 mL,postoperative drainage volume≥800 mL,duration of drainage time≥7 d,albumin＜35 g/L and white blood cell count＜4×109/L were the independent influencing factors of incision infection after modified radical mastectomy(P＜0.05).The peripheral blood levels of PCT,CRP,TNF-α and IL-6 in both groups increased compared with those before surgery,and those in the infected group were higher than those in the non-infected group(P＜0.05).Conclusion:staphylococcus aureus and escherichia coli were the main pathogens after modified radical breast mastectomy.Preoperative neoadjuvant chemotherapy,blood loss≥300 mL,postoperative drainage volume≥800 mL,drainage time≥7 d,albumin＜35 g/L and white blood cell count＜4×109/L were the independent influencing factors.The levels of serum PCT,CRP,TNF-α and IL-6 could be used as effective indicators to predict postoperative incision infection.

Objective To investigate the mechanism of action of Ginkgo biloba extract on schizophrenia based on oxidative stress-mediated damage to PV interneurons.Methods 54 SPF grade male mice were selected as experimental subjects,divided into blank group,model group,ginkgo biloba extract 50 mg·kg-1,100 mg·kg-1,150 mg·kg-1 group,and risperidone group.Schizophrenic mouse models were established by intraperitoneal injection of MK-801 0.3 mg·kg-1,and behavioral(open field experiment,Y-maze,forced swimming)tests were conducted.Blood samples and brain tissue were collected 24 h after the last dose,Immunofluorescence staining was used to detect changes in PV neurons in the mouse brain;Detect the content of MAD,GSH Px,and SOD in serum using a reagent kit;ELISA method was used to detect the levels of iron and lipid peroxidation in mouse brain tissue;Western blot was used to detect the protein level of GPX4 in the mouse brain.Results Compared with the model group,the Ginkgo biloba leaf extract 150 mg·kg-1 group and the risperidone group significantly reduced the spontaneous alternation rate of the Y maze and significantly shortened the immobility time of forced swimming(P<0.05);PV neuron staining with varying degrees of enhanced fluorescence intensity;The MDA content in the serum of mice was significantly reduced(P<0.01),while the contents of SOD and GSH px were significantly increased(P<0.05);The iron content in the mouse brain was significantly reduced(P<0.05),the ROS content was significantly reduced(P<0.05),and the GPX4 content in the mouse brain was significantly increased(P<0.05).Conclusion Ginkgo biloba extract has a significant improvement effect on negative symptoms and cognitive impairment in MK-801 induced schizophrenia mouse models,and can also improve PV neuron damage in the prefrontal cortex of schizophrenia mice.Its mechanism may be related to the inhibition of iron death mediated oxidative stress by Ginkgo biloba extract.

Objective:To investigate the risk factors affecting live birth outcomes in patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) and to establish a predictive model. Methods:A retrospective case-control study was conducted by collecting data from 563 patients with PCOS who were treated at the Reproductive Medicine Department of the General Hospital of Northern Theater Command between June 2018 and January 2023. Patients were divided into live birth ( n=341) and non-live birth ( n=222) groups based on pregnancy outcomes. Univariate and multivariate logistic regression analyses were performed to identify risk factors, followed by construction of a nomogram prediction model based on values with P<0.05 in multiple regression analysis. The model's predictive performance was evaluated using receiver operating characteristic curve analysis, calibration curves, Hosmer-Lemeshow (H-L) goodness-of-fit test, and decision curve analysis. Results:1) Univariate analysis revealed that there were statistically significant differences in age, body mass index (BMI), insulin level, the number of high-quality embryos, and the rate of high-quality embryos between the two groups (all P<0.05). 2) After adjusting for confounding factors, the results of multivariate logistic regression analysis on variables associated with live birth outcomes in the live birth group showed that: age ( OR=1.151, 95% CI: 1.061-1.249, P=0.001), body mass index ( OR=1.141, 95% CI: 1.074-1.214, P<0.001), and insulin level ( OR=1.206, 95% CI: 1.149-1.266, P<0.001) were independent risk factors for live birth outcome; top-quality embryo rate ( OR=0.101, 95% CI: 0.033-0.310, P<0.001) was a protective factor; and the number of top-quality embryos ( OR=0.949, 95% CI: 0.887-1.014, P=0.104) showed no statistically significant association with live birth outcome. 3) A predictive model for the live-birth outcome after IVF/ICSI-ET in PCOS patients was established. The area under the curve (AUC) values for predicting the live-birth outcome based on female age, BMI, the rate of high-quality embryos, and insulin level were 0.581, 0.747, 0.725, and 0.813, respectively. The combined model of these four factors had an AUC value of 0.846 for predicting the live-birth outcome. 4) A nomogram predictive model for the live-birth outcome after IVF/ICSI-ET in PCOS patients was established. The slope of the model's calibration curve was close to 1, and the H-L test yielded a P>0.05, indicating a high consistency between predicted and actual events. The decision analysis curve confirmed the clinical practicality of the predictive model. Conclusion:Age, BMI and insulin level are independent risk factors for live birth outcomes in PCOS patients undergoing IVF/ICSI-ET, while the high-quality embryo rate serves as a protective factor. The established predictive model demonstrates excellent performance and may facilitate clinical decision-making.

AIM:This study aims to investigate the regulatory effects of caffeic acid phenethyl ester(CAPE)on metabotropic glutamate receptor 5(mGluR5)and tyrosine kinase Fyn,and to explore its role in alleviating neuroinflam-mation and pathological features of Alzheimer disease(AD).METHODS:In vitro,the murine neuroblastoma N2a cell line was treated with amyloid β-protein 42 oligomers(Aβ42Os;10 nmol/L to 10 μmol/L)for 24 h.Cell viability was as-sessed by MTT assay.Western blot analyzed mGluR5 expression and Fyn phosphorylation(Tyr416).Pharmacological modulators(CHPG/MPEP)were used to evaluate mGluR5-mediated inflammatory cytokine regulation(qPCR)and Fyn ac-tivation.In vivo,wild-type(WT)and 5×FAD mice(WT,WT+CAPE,5×FAD and 5×FAD+CAPE)were analyzed for AD-related proteins,neuroinflammation(ELISA),glial activation(GFAP/Iba-1 immunofluorescence),and β-amyloid deposi-tion(thioflavin S).RESULTS:(1)Treatment with 1 μmol/L Aβ42Os increased mGluR5 expression(P<0.01)and Fyn phosphorylation(P<0.01)without affecting N2a cell viability.Intracerebral Aβ42Os injection similarly up-regulated hip-pocampal mGluR5 and Fyn(P<0.01).(2)MPEP reduced mGluR5 expression(P<0.01)and Fyn phosphorylation(P<0.01),while suppressing tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)mRNA levels(P<0.01).(3)CAPE decreased mGluR5-Fyn activation in N2a cells,neurons,and 5×FAD mice(P<0.01).(4)CAPE-treated 5×FAD mice exhibited reduced neuroinflammation markers(GFAP,Iba-1,TNF-α,IL-1β,and IL-6),Aβ plaques,and p-APP levels(P<0.01).CONCLUSION:Treatment with CAPE inhibits Aβ42Os-induced mGluR5-Fyn signaling activation,thereby attenuating neuroinflammation and the pathology associated with AD.

Based on the theory of the liver's"using bitter herbs to nourish or purge"from Huangdi Neijing,this paper systematically elucidates the theoretical foundation for treating functional constipation from liver.Focusing on the physiological characteristic of"liver desires to disperse"and the pathological manifestation of"liver bitterness and urgency,"combined with the"liver communicates with the large intestine"theory,this paper establishes a diagnostic and therapeutic framework for managing functional constipation by regulating liver function.The pathological evolution of functional constipation manifests in three distinct stages:in the early stage,liver qi stagnation leads to large intestine qi obstruction,where damaged by an excess of seven emotions resulting in symptoms such as difficult defecation,abdominal bloating,and hypochondriac pain;in the middle stage,liver depression transforms into fire,scorching bodily fluids to generate dryness,thereby creating a pathological interplay of stagnation,fire,and dryness,which is marked by anal heat,dry mouth,and yellow urine;in the late stage,yin deficiency in liver and kidney causes large intestine malnutrition,resulting in a complex pathological state where yin deficiency,collateral blockage,dryness accumulation,and blood stasis intertwine,clinically manifesting as pellet-like stools(resembling sheep feces)and soreness and weakness of the waist and knees.In treatment,the formula design follows the principle of"sweetness to relieve,acridity to tonify,and sourness to purge,"with treatment principles varying across stages.In the early stage,the focus is on dispersing liver and regulating qi,and unblocking the zang-fu viscera;in the middle stage,the priority shifts to clearing heat-fire,nourishing large intestine,and promoting fluid production;whereas,in the late stage,the emphasis lies on nourishing yin,unblocking collaterals,and promoting blood circulation.This staged treatment of functional constipation overcomes the limitations of solely focusing on nourishing large intestine and facilitating feces excretion,thereby advancing the treatment of different stages based on syndrome differentiation and personalized treatment.It provides theoretical support for improving patients' intestinal function and enhancing overall health outcomes.

Objective:To investigate the risk factors affecting live birth outcomes in patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) and to establish a predictive model. Methods:A retrospective case-control study was conducted by collecting data from 563 patients with PCOS who were treated at the Reproductive Medicine Department of the General Hospital of Northern Theater Command between June 2018 and January 2023. Patients were divided into live birth ( n=341) and non-live birth ( n=222) groups based on pregnancy outcomes. Univariate and multivariate logistic regression analyses were performed to identify risk factors, followed by construction of a nomogram prediction model based on values with P<0.05 in multiple regression analysis. The model's predictive performance was evaluated using receiver operating characteristic curve analysis, calibration curves, Hosmer-Lemeshow (H-L) goodness-of-fit test, and decision curve analysis. Results:1) Univariate analysis revealed that there were statistically significant differences in age, body mass index (BMI), insulin level, the number of high-quality embryos, and the rate of high-quality embryos between the two groups (all P<0.05). 2) After adjusting for confounding factors, the results of multivariate logistic regression analysis on variables associated with live birth outcomes in the live birth group showed that: age ( OR=1.151, 95% CI: 1.061-1.249, P=0.001), body mass index ( OR=1.141, 95% CI: 1.074-1.214, P<0.001), and insulin level ( OR=1.206, 95% CI: 1.149-1.266, P<0.001) were independent risk factors for live birth outcome; top-quality embryo rate ( OR=0.101, 95% CI: 0.033-0.310, P<0.001) was a protective factor; and the number of top-quality embryos ( OR=0.949, 95% CI: 0.887-1.014, P=0.104) showed no statistically significant association with live birth outcome. 3) A predictive model for the live-birth outcome after IVF/ICSI-ET in PCOS patients was established. The area under the curve (AUC) values for predicting the live-birth outcome based on female age, BMI, the rate of high-quality embryos, and insulin level were 0.581, 0.747, 0.725, and 0.813, respectively. The combined model of these four factors had an AUC value of 0.846 for predicting the live-birth outcome. 4) A nomogram predictive model for the live-birth outcome after IVF/ICSI-ET in PCOS patients was established. The slope of the model's calibration curve was close to 1, and the H-L test yielded a P>0.05, indicating a high consistency between predicted and actual events. The decision analysis curve confirmed the clinical practicality of the predictive model. Conclusion:Age, BMI and insulin level are independent risk factors for live birth outcomes in PCOS patients undergoing IVF/ICSI-ET, while the high-quality embryo rate serves as a protective factor. The established predictive model demonstrates excellent performance and may facilitate clinical decision-making.

Objective:To investigate the role of Gasdermin E (GSDME) -mediated keratinocyte pyroptosis induced by Cutibacterium acnes ( C.acnes) in the pathogenesis of acne. Methods:The human immortalized keratinocyte HaCaT cells were stimulated with heat-inactived C.acnes for 15 minutes to 24 hours, and Western blot analysis was performed to determine the expression of cleaved GSDME (GSDME-NT) in HaCaT cells at different time points. Skin tissue samples were collected from 5 acne patients and 4 healthy controls, who visited the Hospital for Skin Diseases, Chinese Academy of Medical Sciences from January 2 to December 1, 2024; additionally, 3 samples of acne cyst contents and 3 samples of normal follicle contents were collected. Immunohistochemical study and Western blot analysis were conducted to determine GSDME-NT expression in the epidermis. Enzyme-linked immunosorbent assay (ELISA) was performed to detect levels of interleukin (IL) -1β and tumor necrosis factor (TNF) -α in acne cyst or normal follicle contents. GSDME-knockdown HaCaT cells were constructed by transfection with lentivirus carrying GSDME-shRNA, and HaCaT cells transfected with lentivirus carrying the nonsense sequence control (NC) served as controls; ELISA was performed to detect the levels of IL-1β and TNF-α in GSDME-knockdown HaCaT cells after C. acnes stimulation ( C. acnes + GSDME knockdown group) , as well as in the phosphate-buffered saline (PBS) + NC group, C. acnes + NC group, and PBS + GSDME knockdown group. Western blot analysis was conducted to determine the GSDME-NT expression in HaCaT cells pretreated with or without retinol after C. acnes stimulation. Results:The cleavage of GSDME in HaCaT cells began at 1 hour after in vitro C. acnes stimulation, and GSDME-NT could be detected at this time. Compared with the control epidermis, the proportion of GSDME-NT-positive HaCaT cells (9.34% ± 2.92% vs. 3.05% ± 1.14%, t = -3.47, P = 0.026) and GSDME-NT protein expression levels ( t = -3.51, P = 0.025) significantly increased in the lesional epidermis of acne patients. The levels of IL-1β and TNF-α were significantly higher in the acne cyst contents than in the normal follicle contents (IL-1β: 1 337.24 [1 182.32, 2 230.61] pg/ml vs. 0.00 [0.00, 108.21] pg/ml, Z = 1.99, P = 0.046; TNF-α: 811.31 [438.26, 817.73] pg/ml vs. 46.67 [12.41, 53.21] pg/ml, Z = 1.96, P = 0.049) . ELISA showed that the levels of IL-1β and TNF-α were significantly higher in the C. acnes + NC group (12.12 ± 3.07 pg/ml, 26.06 ± 1.57 pg/ml, respectively) than in the PBS + NC group (3.73 ± 2.24 pg/ml, 10.14 ± 0.79 pg/ml, P = 0.003, < 0.001, respectively) ; compared with the C. acnes + NC group, the levels of IL-1β and TNF-α significantly decreased in the C. acnes + GSDME knockdown group (3.38 ± 0.93 pg/ml, 12.67 ± 2.10 pg/ml, P = 0.003, < 0.001, respectively) . The GSDME-NT expression was significantly lower in the retinol + C. acnes group than in the C. acnes group ( P = 0.029) . Conclusion:C. acnes may induce GSDME-mediated pyroptosis in keratinocytes, thereby promoting the release of inflammatory factors and aggravating the inflammatory response in acne, while retinol may be able to inhibit this process.

Objective:This study aimed to analyze the genetic variation of the human papillomavirus (HPV) type 39 genomes and to predict and screen the dominant T-cell and B-cell epitopes of the viral early proteins (E1, E2, E6, E7) and late proteins (L1, L2).Methods:A total of 70 full-length sequences of HPV39 variants were retrieved from the clinical samples and the National Center for Biotechnology Information (NCBI) to construct a phylogenetic tree, analyze genetic polymorphisms, and predict the physicochemical properties of the viral proteins. Next, T-cell and B-cell epitopes were predicted using IEDB and ABCpred, and potential dominant epitopes were further selected based on parameters such as the secondary structure of the epitope region, peptide flexibility, hydrophilicity, surface accessibility and antigenicity. Finally, a homology analysis of the potential dominant epitopes was performed with 12 high-risk HPV types.Results:HPV39 variants from different sources can be clustered into two lineages (A and B), each exhibiting distinct mutation patterns. The mutation rate was the highest in E7 and the lowest in E1 among the different viral genes. However, these nucleotide/amino acid mutations did not significantly impact the physicochemical properties of the viral proteins. After prediction and screening, 5 and 6 potential dominant B-cell epitopes were identified in both L1 and L2, respectively. E1, E2, E6, and E7 yielded 18, 10, 4, and 1 potential dominant HLA-I restricted T-cell epitopes, respectively. Additionally, E1, E2, and E6 yielded 7, 3, and 2 potential dominant HLA-II restricted T-cell epitopes, respectively. Homology analysis indicated that T-cell dominant epitopes in E1, E2, and E6, as well as B-cell epitopes in L2, showed high homology (93%-100%) with HPV68, HPV33, HPV45, and HPV59.Conclusions:Bioinformatics analysis and prediction revealed that HPV39 variants can be clustered into two main evolutionary branches, A and B, each exhibiting a specific mutation pattern. The viral proteins contain potential dominant T-cell and B-cell epitopes that can be further investigated, providing valuable theoretical support for the development of HPV39-related peptide-based vaccines and therapeutics.