This paper summarizes Professor SHI Zaixiang's clinical experience in treating high fever caused by sepsis using Chaihu Guizhi Ganjiang Decoction （柴胡桂枝干姜汤）. He holds that the key pathogenesis of sepsis involves constrained heat in the shaoyang and internal accumulation of water and fluids. The clinical manifestations such as high fever， chills， and alternating sensations of cold and heat are attributed to pathogenic heat constrained in the shaoyang. Meanwhile， soft tissue edema and serous cavity effusions are due to shaoyang dysfunction and internal water retention. In clinical practice， treating sepsis-related high fever requires addressing both the shaoyang-constrained heat and the associated edema and effusions. The therapeutic approach focuses on harmonizing the shaoyang and resolving internal fluids， using Chaihu Guizhi Ganjiang Decoction as the base formula with flexible modifications. Professor SHI emphasizes that this formula shows a rapid antipyretic effect， particularly in cases where multiple anti-infective treatments have failed.

Episodic memory, our ability to recall past experiences, is supported by structures in the medial temporal lobe (MTL) particularly the hippocampus, and its interactions with fronto-parietal brain regions. Understanding how these brain regions coordinate to encode, consolidate, and retrieve episodic memories remains a fundamental question in cognitive neuroscience. Non-invasive brain stimulation (NIBS) methods, especially transcranial magnetic stimulation (TMS), have advanced episodic memory research beyond traditional lesion studies and neuroimaging by enabling causal investigations through targeted magnetic stimulation to specific brain regions. This review begins by delineating the evolving understanding of episodic memory from both psychological and neurobiological perspectives and discusses the brain networks supporting episodic memory processes. Then, we review studies that employed TMS to modulate episodic memory, with the aim of identifying potential cortical regions that could be used as stimulation sites to modulate episodic memory networks. We conclude with the implications and prospects of using NIBS to understand episodic memory mechanisms.
Humans ; Memory, Episodic ; Transcranial Magnetic Stimulation/methods* ; Brain/physiology* ; Nerve Net/physiology* ; Mental Recall/physiology* ; Neural Pathways/physiology*

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

Colorectal inflammatory cancer transformation poses a major risk to patients with colitis. Patients with chronic intestinal inflammation have an approximately 2-3 folds increased risk of developing colorectal cancer (CRC). Unfortunately, there is currently no effective intervention available. Huangqin decoction (HQD), a well-known traditional Chinese medicine (TCM) formula, is frequently clinically prescribed for treating patients with colitis, and its active ingredients have effective antitumour efficacy. Nonetheless, the mechanism of HQD-mediated prevention of colorectal inflammatory cancer transformation remains unclear. A strategy integrating metagenomic, lipidomic, and messenger RNA (mRNA) sequencing analysis was used to investigate the regulatory effects of HQD on the gut microbiome, metabolism and potential mechanisms involved in colorectal inflammatory cancer transformation. Our study revealed that HQD suppressed colorectal inflammatory cancer transformation, which was associated with enhanced intestinal barrier function, decreased the inflammatory response, and regulation of the gut microbiome. Notably, cohousing experiments revealed that the transfer of the gut microbiome from HQD-treated mice largely inhibited the pathological transformation of colitis. Moreover, gut microbiome transfer from HQD-treated mice primarily resulted in the altered regulation of fatty acid metabolism, especially the remodeling of arachidonic acid metabolism, which was associated with the amelioration of pathological transformation. Arachidonic acid metabolism and the key metabolic enzyme arachidonic acid 12-lipoxygenase (ALOX12) were affected by HQD treatment, and no obvious protective effect of HQD was observed in Alox 12 ^-/- mice, which revealed that ALOX12 was a critical mediator of HQD protection against colorectal inflammatory cancer transformation. In summary, multiple omics analyses were applied to produce valuable data and theoretical support for the application of HQD as a promising intervention for the transformation of inflammatory CRC.

OBJECTIVE: Exposure to polycyclic aromatic hydrocarbons (PAHs) or metal(loid)s individually has been associated with neural tube defects (NTDs). However, the impacts of PAH and metal(loid) co-exposure and potential interaction effects on NTD risk remain unclear. We conducted a case-control study in China among population with a high prevalence of NTDs to investigate the combined effects of PAH and metal(loid) exposures on the risk of NTD. METHODS: Cases included 80 women who gave birth to offspring with NTDs, whereas controls were 50 women who delivered infants with no congenital malformations. We analyzed the levels of placental PAHs using gas chromatography and mass spectrometry, PAH-DNA adducts with ³²P-post-labeling method, and metal(loid)s with an inductively coupled plasma mass spectrometer. Unconditional logistic regression was employed to estimate the associations between individual exposures and NTDs. Least absolute shrinkage and selection operator (LASSO) penalized regression models were used to select a subset of exposures, while additive interaction models were used to identify interaction effects. RESULTS: In the single-exposure models, we found that eight PAHs, PAH-DNA adducts, and 28 metal(loid)s were associated with NTDs. Pyrene, selenium, molybdenum, cadmium, uranium, and rubidium were selected through LASSO regression and were statistically associated with NTDs in the multiple-exposure models. Women with high levels of pyrene and molybdenum or pyrene and selenium exhibited significantly increased risk of having offspring with NTDs, indicating that these combinations may have synergistic effects on the risk of NTDs. CONCLUSION Our findings suggest that individual PAHs and metal(loid)s, as well as their interactions, may be associated with the risk of NTDs, which warrants further investigation.
Humans ; Neural Tube Defects/chemically induced* ; Polycyclic Aromatic Hydrocarbons/adverse effects* ; Female ; Case-Control Studies ; China/epidemiology* ; Adult ; Pregnancy ; Environmental Pollutants ; Maternal Exposure/adverse effects* ; Metals/toxicity* ; Young Adult ; Risk Factors

ObjectiveTo investigate the potential mechanism of Liangxue Tuizi Formula （凉血退紫方， LXTZF） in treating Henoch-Schönlein Purpura （HSP） by examining its regulatory effect on neutrophil extracellular trap （NETs） dysregulation via the rapidly accelerated fibrosarcoma kinase （RAF）/mitogen-activated protein kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway. MethodsSeventy Wistar rats were randomly allocated into a blank control group （n=14） and a modeling group （n=56）. Rats in the modelling group underwent an eight-week modelling period to establish HSP rat models with blood-heat syndrome via modified ovalbumin （OVA） induction method combined with oral administration of heat-property Chinese herbal medicine. Fifty successfully modeled rats were subsequently randomly divided into five groups （n=10 per group）， model group， compound glycyrrhizin group， LXTZF group， RAF inhibitor group， and LXTZF + RAF agonist group. Additionally， 10 rats were selected from the original blank control group for the final experiment. From the 11th week of modelling， rats in the blank control group and the model group received 1 ml/（100 g·d） ultrapure water via oral administration， in addition to 0.5 ml/（kg·d） 0.9% sodium chloride solution via intraperitoneal injection. The LXTZF group and the compound glycyrrhizin group received 7.5 g/（kg·d） LXTZF granule suspension via gavage， 13.5 mg/（kg·d） compound glycyrrhizin suspension via gavage， respectively. The RAF inhibitor group received 1 mg/（kg·d） GW5074 suspension via intraperitoneal injection and ultrapure water via oral administration； the LXTZF + RAF agonist group received 7.5 g/（kg·d） LXTZF granule suspension via gavage and 1 mg/（kg·d） paclitaxel suspension via intraperitoneal injection. All administrations were performed once daily for 4 weeks. After intervention， skin tissue histopathology was examined by hematoxylin and eosin （H&E） staining， immunoglobulin A （IgA） deposition was assessed via immunofluorescence， serum levels of neutrophil elastase （NE）， tumor necrosis factor-α （TNF-α）， and vascular cell adhesion molecule-1 （VCAM-1） were measured using enzyme-linked immunosorbent assay （ELISA）， serum myeloperoxidase （MPO） level was determined by a colorimetric assay； the mRNA expression levels of RAF， MEK， and ERK in skin tissue were detected by real-time quantitative polymerase chain reaction （RT-qPCR）； and the protein expression of RAF， MEK， ERK， as well as phosphorylated MEK （p-MEK） and phosphorylated ERK （p-ERK）， were analyzed by Western Blot. ResultsSkin tissue in the blank control group rats remained normal， whereas the model group exhibited neutrophil infiltration and haemorrhage with red blood cell rupture. In all drug intervention groups， neutrophil infiltration and haemorrhagic exudation reduced markedly， with LXTZF group demonstrating the most pronounced improvement. Compared with the blank control group， rats in the model group exhibited enhanced IgA fluorescence intensity in skin tissue， elevated serum levels of NE， MPO， TNF-α and VCAM-1， increased mRNA expression of RAF， MEK， ERK1 and ERK2， as well as heightened RAF protein levels and p-MEK/MEK and p-ERK/ERK ratios （P＜0.05）. Compared with the model group， the drug intervention groups exhibited reduced IgA fluorescence intensity in skin tissue， along with decreased serum levels of NE， MPO， TNF-α， and VCAM-1 （P＜0.05）. In LXTZF group and RAF inhibition groups， reduced mRNA expression of RAF， MEK， ERK1， and ERK2 was observed in rat skin tissue， alongside decreased RAF protein levels and reduced p-MEK/MEK and p-ERK/ERK ratios （P＜0.05）. Compared with LXTZF + RAF agonist group， the compound glycyrrhizin group， LXTZF group， and RAF inhibitior group exhibited reduced IgA fluorescence intensity in skin tissue， decreased serum NE， MPO， TNF-α， and VCAM-1 levels， and decreased MEK mRNA expression and p-MEK/MEK ratio （P＜0.05）. ConclusionThe potential mechanism by which LXTZF treats Henoch-Schönlein purpura with blood heat syndrome may involve blocking the RAF/MEK/ERK signaling pathway in skin tissue， and suppressing excessive formation of NETs， thereby reducing IgA deposition in dermal microvessels and attenuating systemic inflammatory responses.

Objective:To investigate the association between homocysteine (Hcy) and recurrent pregnancy loss (RPL), as well as its impact on clinical pregnancy outcomes in patients undergoing in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET). Methods:This retrospective cohort study collected clinical data from patients undergoing IVF/ICSI-ET at the Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University between December 2020 and March 2024. Patients were divided into no history of pregnancy loss group (named control group, n=1 027) and RPL group ( n=743) based on history of pregnancy loss. Peripheral blood Hcy levels were compared between the two groups. Multivariate logistic regression was performed to adjust for confounding factors and determine whether Hcy is an independent risk factor for RPL. RPL patients were divided into four subgroups based on Hcy quartiles, named Q1 subgroup (Hcy<7.03 μmol/L), Q2 subgroup (7.03 μmol/L≤Hcy<8.63 μmol/L), Q3 subgroup (8.63 μmol/L≤Hcy<10.44 μmol/L), and Q4 subgroup (Hcy≥10.44 μmol/L), to further analyze the impact of Hcy level on pregnancy outcomes after IVF/ICSI-ET in these patients. Results:1) Baseline characteristics between control and RPL groups: statistically significant differences were observed in female age, male age, female body mass index (BMI), duration of infertility, cause of infertility, and peripheral blood Hcy levels (all P<0.05). 2) After adjusting for female age, male age, female BMI, duration of infertility, and cause of infertility via multivariate logistic regression, elevated Hcy levels was identified as an independent risk factor for RPL (a OR=1.366, 95% CI: 1.298-1.438, P<0.001). 3) Baseline characteristics of the four RPL subgroups: antral follicle count (AFC) differed significantly among Q1, Q2, Q3 and Q4 subgroups [17.00 (11.00, 24.00), 15.00 (10.00, 24.00), 14.00 (7.00, 22.25), 15.50 (8.00, 22.00), P=0.043]. No statistically significant differences were observed in other baseline characteristics (all P>0.05). 4) Pregnancy outcomes across the four RPL subgroups: miscarriage rates in the Q1, Q2, Q3 and Q4 subgroups were 18.18% (18/99), 30.61% (30/98), 33.70% (31/92), and 35.96% (32/89), respectively, live birth rates were 44.26% (81/183), 36.17% (68/188), 32.80% (61/186), and 30.65% (57/186), respectively. Intergroup differences in miscarriage rate and live birth rate were statistically significant ( P=0.033, P=0.036). Specifically, miscarriage rate in the Q3 and Q4 subgroups, and live birth rate in the Q4 subgroup were significantly higher than those in the Q1 subgroup (all q<0.05). However, no significant differences were observed in clinical pregnancy rate or early miscarriage rate among the four groups (all P>0.05). After adjusting for confounding factors using multivariate logistic regression, taking the Q1 subgroup as the control, there were no statistically significant differences in the clinical pregnancy rate between the remaining groups and the Q1 subgroup (all P>0.05). The early miscarriage rate in the Q3 subgroup (a OR=2.184, 95% CI: 1.077-4.426, P=0.030) and the early miscarriage rate in the Q4 subgroup (a OR=2.290, 95% CI: 1.116-4.697, P=0.024) were significantly higher than those in the Q1 subgroup; the miscarriage rate in the Q3 subgroup (a OR=2.207, 95% CI: 1.125-4.330, P=0.021) and the miscarriage rate in the Q4 subgroup (a OR=2.377, 95% CI: 1.209-4.674, P=0.012) were significantly higher than those in the Q1 subgroup; the live birth rate in the Q3 subgroup (a OR=0.615, 95% CI: 0.401-0.944, P=0.026) and the live birth rate in the Q4 subgroup (a OR=0.560, 95% CI: 0.364-0.863, P=0.009) were significantly lower than those in the Q1 subgroup. Conclusion:Elevated Hcy is a high-risk factor for RPL in IVF/ICSI-ET patients and may adversely affect pregnancy outcomes.

Objective:To investigate the association between homocysteine (Hcy) and recurrent pregnancy loss (RPL), as well as its impact on clinical pregnancy outcomes in patients undergoing in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET). Methods:This retrospective cohort study collected clinical data from patients undergoing IVF/ICSI-ET at the Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University between December 2020 and March 2024. Patients were divided into no history of pregnancy loss group (named control group, n=1 027) and RPL group ( n=743) based on history of pregnancy loss. Peripheral blood Hcy levels were compared between the two groups. Multivariate logistic regression was performed to adjust for confounding factors and determine whether Hcy is an independent risk factor for RPL. RPL patients were divided into four subgroups based on Hcy quartiles, named Q1 subgroup (Hcy<7.03 μmol/L), Q2 subgroup (7.03 μmol/L≤Hcy<8.63 μmol/L), Q3 subgroup (8.63 μmol/L≤Hcy<10.44 μmol/L), and Q4 subgroup (Hcy≥10.44 μmol/L), to further analyze the impact of Hcy level on pregnancy outcomes after IVF/ICSI-ET in these patients. Results:1) Baseline characteristics between control and RPL groups: statistically significant differences were observed in female age, male age, female body mass index (BMI), duration of infertility, cause of infertility, and peripheral blood Hcy levels (all P<0.05). 2) After adjusting for female age, male age, female BMI, duration of infertility, and cause of infertility via multivariate logistic regression, elevated Hcy levels was identified as an independent risk factor for RPL (a OR=1.366, 95% CI: 1.298-1.438, P<0.001). 3) Baseline characteristics of the four RPL subgroups: antral follicle count (AFC) differed significantly among Q1, Q2, Q3 and Q4 subgroups [17.00 (11.00, 24.00), 15.00 (10.00, 24.00), 14.00 (7.00, 22.25), 15.50 (8.00, 22.00), P=0.043]. No statistically significant differences were observed in other baseline characteristics (all P>0.05). 4) Pregnancy outcomes across the four RPL subgroups: miscarriage rates in the Q1, Q2, Q3 and Q4 subgroups were 18.18% (18/99), 30.61% (30/98), 33.70% (31/92), and 35.96% (32/89), respectively, live birth rates were 44.26% (81/183), 36.17% (68/188), 32.80% (61/186), and 30.65% (57/186), respectively. Intergroup differences in miscarriage rate and live birth rate were statistically significant ( P=0.033, P=0.036). Specifically, miscarriage rate in the Q3 and Q4 subgroups, and live birth rate in the Q4 subgroup were significantly higher than those in the Q1 subgroup (all q<0.05). However, no significant differences were observed in clinical pregnancy rate or early miscarriage rate among the four groups (all P>0.05). After adjusting for confounding factors using multivariate logistic regression, taking the Q1 subgroup as the control, there were no statistically significant differences in the clinical pregnancy rate between the remaining groups and the Q1 subgroup (all P>0.05). The early miscarriage rate in the Q3 subgroup (a OR=2.184, 95% CI: 1.077-4.426, P=0.030) and the early miscarriage rate in the Q4 subgroup (a OR=2.290, 95% CI: 1.116-4.697, P=0.024) were significantly higher than those in the Q1 subgroup; the miscarriage rate in the Q3 subgroup (a OR=2.207, 95% CI: 1.125-4.330, P=0.021) and the miscarriage rate in the Q4 subgroup (a OR=2.377, 95% CI: 1.209-4.674, P=0.012) were significantly higher than those in the Q1 subgroup; the live birth rate in the Q3 subgroup (a OR=0.615, 95% CI: 0.401-0.944, P=0.026) and the live birth rate in the Q4 subgroup (a OR=0.560, 95% CI: 0.364-0.863, P=0.009) were significantly lower than those in the Q1 subgroup. Conclusion:Elevated Hcy is a high-risk factor for RPL in IVF/ICSI-ET patients and may adversely affect pregnancy outcomes.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Objective:To analyze the predictive role of WT1 expression levels pre-and early post-transplantation on relapse and overall survival(OS)in patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)during their first complete remission(CR1).Methods:A retrospective analysis was conducted on the clinical data of 107 adult AML patients who underwent allo-HSCT during their CR1 at our center between May 2012 and December 2021.The predictive role of bone marrow WT1 expression levels before transplantation and at 3 and 6 months post-transplantation on relapse and OS was explored in combination with relevant clinical factors.Results:The median follow-up time for the 107 patients was 70(range:11-117)months.Among the patients,15 cases died.Kaplan-Meier survial analysis showed that the 3-year overall survival(OS)rate was 85.0％.20 patients experienced relapse,with a median time to relapse of 8(range:0.5-44)months and a l-year cumulative relapse rate of 13.1％.The overall median value of WT1 before transplantation,3 months after transplantation,and 6 months after transplantation was 0.26％(range:0％-23.64％),with an upper quartile value of 0.74％.No statistically significant differences in WT1 expression levels were observed among the pre-transplantation,3-month post-transplantation,and 6-month post-transplantation time points(P=0.227).Univariate analysis showed that patients with WT1 levels＞0.74％at 3 months post-transplantation had a higher 1-year relapse rate(P=0.029)and lower 3-year OS rate(P＜0.001)compared to patients with WT1 levels ≤0.74％.Other significant factors affecting 1-year relapse included stem cell source(P=0.041)and chronic graft-versus-host disease(cGVHD)(P=0.013).For 3-year OS,additional influencing factors were genetic high risk(P=0.048)and stem cell source(P=0.016).Multivariate analysis revealed that WT1 level＞0.74％at 3 months post-transplantation had a trend to affect 1-year relapse rate(HR=3.309,95％CI:0.958-11.431,P=0.058),while the absence of cGVHD was an independent risk factor for 1-year relapse(HR=3.473,95％CI:0.749-16.100,P=0.037).Only WT1 level＞0.74％at 3 months post-transplantation was an independent risk factor for 3-year OS(HR=6.886,95％CI:2.402-19.738,P＜0.001).Conclusion:High WT1 expression level at 3 months post-transplantation in AML patients undergoing allo-HSCT during CR1 affects the 1-year relapse rate and 3-year OS,and is an independent risk factor affecting 3-year OS.These findings suggest that dynamic monitoring of WT1 expression levels has certain value in prognostic assessment of AML patients who received allo-HSCT during CR1.