Objective:To investigate the role and analgesic mechanism of ginsenoside Rg1(GRg1)in neuropathic pain in rats.Methods:A total of 30 adult male Sprague-Dawley rats were randomly divided into sham-operation group,spared nerve injury(SNI)group,GRg1 group,GRg1+empty vector group(GRg1+vector group),and GRg1+TLR4 overexpression plasmid group(GRg1+TLR4 group),with 6 rats in each group.The SNI method was used to establish a rat model of neuropathic pain in the latter four groups,and after successful modeling,GRg1 was given by gavage for 14 days,while the plasmid was injected via the caudal vein.The sciatic nerve was exposed for the sham-operation group without any injury manipulation.A mechanical pain threshold detector and a radiation thermal pain threshold detector were used to measure mechanical withdrawal threshold and thermal withdrawal latency on day 1 before surgery and on days 1,3,7,and 14 after surgery.L4-L6 spinal cord tissue samples were collected,and quantitative real-time PCR,Western blot,and indirect immunofluorescence assay were used to measure the mRNA and protein expression levels of GFAP,a marker for astrocyte activation,and Iba-1,a marker for microglial cells;ELISA was used to measure the content of IL-1β,TNF-α,and CXCL1 in spinal cord tissue,and colorimetry was used to mea-sure the content of NO in spinal cord tissue;molecular docking was used to investigate the binding ability and interaction mode between GRg1 and TLR4.Results:GRg1 restored mechanical withdrawal threshold(F=24.67,P=0.000)and thermal withdrawal latency in SNI rats(F=8.058,P=0.034)and downregulated the expression lev-els of GFAP(mRNA:F=37.74,P=0.000;protein:F=98.71,P=0.001)and Iba-1(mRNA:F=62.11,P=0.000;protein:F=187.0,P=0.000)in spinal cord tissues of SNI rats,and it also reduced the levels of IL-1β(F=56.96,P=0.000),TNF-α(F=55.25,P=0.000),CXCL1(F=93.54,P=0.000)and NO(F=30.57,P=0.000)in the spinal cord tissues of SNI rats.The study on mechanisms showed highly stable binding between GRg1 and TLR4,and GRg1 downregulated the expression level of TLR4(mRNA:F=62.66,P=0.000;protein:F=53.52,P=0.000)and the phosphorylation levels of p38(F=300.3,P=0.000)and p65(F=121.6,P=0.000)in spinal cord tis-sues of SNI rats,whereas the overexpression of TLR4 reversed the effect of GRg1(Mechanical Paw Withdrawal Threshold:F=24.67,P=0.000;Thermal Paw Withdrawal Latency:F=8.058,P=0.034;GFAP,mRNA:F=37.74,P=0.009;Protein:F=98.71,P=0.000;Iba-1,mRNA:F=62.11,P=0.006;Protein:F=187.0,P=0.000;IL-1β:F=56.96,P=0.006;TNF-α:F=55.25,P=0.000;CXCL1:F=93.54,P=0.000;NO:F=30.57,P=0.042;TLR4,mRNA:F=62.66,P=0.000;Protein:F=53.52,P=0.000;p38 Phosphorylation Level:F=300.3,P=0.000;p65 Phosphorylation Level:F=121.6,P=0.000).Conclusion:GRg1 may exert an analgesic effect on SNI rats by regulating the TLR4-p38/MAPK-NF-κB signaling pathway and activating the activation of astrocytes and microglial cells in spinal cord tissue.

Objective: To analyze the spatio-temporal distribution of pulmonary tuberculosis (PTB) among students in Suzhou City, Jiangsu Province from 2015 to 2023, so as to provide the evidence for the prevention and control of PTB in schools. Methods: Data of PTB cases among students in Suzhou City from 2015 to 2023 were collected from Chinese Disease Prevention and Control Information System and Suzhou Report of Investigation and Disposal of Tuberculosis in Schools. The seasonal incidence of PTB among students was analyzed using seasonal index (SI). The spatio-temporal clustering characteristics of PTB among students were analyzed using spatial autocorrelation and retrospective spatio-temporal permutation scanning. Results: Totally 1 374 PTB cases among students were reported in Suzhou City from 2015 to 2023. PTB cases were reported in each month, and the SIs were 100.69%, 124.38%, 108.98%, 135.04%, 106.61% and 106.61% in April, May, July, September, October and November, respectively, indicating the prevalence of PTB among students. Spatial autocorrelation analysis showed there was a positive spatial correlation of PTB among students in 2019 and 2020 (Moran's I=0.053 and 0.089, both P<0.05). From 2015 to 2023, there were high-high clustering sites mainly in Hengtang Street and Shishan Street. Retrospective spatio-temporal permutation scanning showed a primary cluster in Hengtang Street, with aggregation time in 2017, and 6 secondary clusters covering 25 towns (streets). Conclusion From 2015 to 2023, the PTB cases among students in Suzhou City were mainly concentrated in summer and autumn, and were predominantly clustered in Hengtang Street and Shishan Street.

Myocardial infarction (MI) is the leading cause of cardiovascular disease-related death worldwide. Nonetheless, existing therapeutic approaches for MI are hampered by issues such as reliance on pharmacological agents and suboptimal patient adherence. Caffeic acid (CA) is a bioactive polyphenolic compound with important anti-inflammatory, anti-bacterial and anti-oxidant functions. Still, its specific role and mechanism in treating cardiovascular disease remain to be further studied. In recent years, a large number of studies have shown that the kelch-like ECH-associated protein 1/nuclear factor erythroid 2 related factor 2 (Keap1/Nrf2) pathway is a key factor in the occurrence and development of cardiovascular diseases. In this study, H₂O₂-induced oxidative stress model of H9c2 cells and left anterior descending branch (LAD) conjunctival induced acute myocardial infarction reperfusion (AMI/R) model were used to evaluate the protective effect of CA on the heart. The interaction between CA and Keap1 was analyzed by CA-labeled fluorescence probe, target fishing, isothermal titration calorimetry (ITC), protein crystallography and surface plasmon resonance (SPR). Our results suggested that CA binds Keap1 and degrades Keap1 in a p62-dependent manner, further promoting nuclear transcription of Nrf2 and thus effectively reducing oxidative stress. In addition, based on the three-dimensional eutectic structure, it was confirmed that CA directly targets Keap1 protein by interacting with residues M550 and N532, inducing conformation changes in Keap1 protein. We also found that the CA analog chlorogenic acid (GCA) can bind Keap1. In conclusion, this study elucidates a novel molecular mechanism and structural basis for the protective effects of CA against oxidative damage via the Keap1-Nrf2 pathway.

Objective To investigate the effects of miR-139-5p-modified human umbilical cord mensenchymal stem cell(UC-MSC)-derived exosomes on stemness and radiotherapy sensitivity of breast cancer cells.Methods MCF-7 cells were divided into the control,miR-NC Exo,and miR-139-5p Exo groups.Immunofluorescence staining was used to observe the cellular uptake of exosomes.A tumor sphere formation assay determined the number of tumor spheres formed.Western blotting detected NANOG,SOX2,and OCT4 protein expression levels.MCF-7 cells were divided into control,2 Gy X ray,miR-139-5p Exo,and miR-139-5p Exo+2 Gy X ray groups.The survival rate of MCF-7 cells was detected by the MTT method.The apoptosis rate of MCF-7 cells was determined using flow cytometry.Results Compared to the control and miR-NC Exo groups,the number of tumor spheres formed by MCF-7 cells in the miR-139-5p Exo group was significantly decreased,and the relative expression levels of Nanog,SOX2,and OCT4 proteins were significantly downregulated(P＜0.05).Compared to the control group,the survival rate of MCF-7 cells in the 2 Gy X ray and miR-139-5p Exo groups was significantly decreased,and the apoptosis rate was significantly increased(P＜0.05).Compared to the 2 Gy X ray group,the survival rate of MCF-7 cells in the miR-139-5p Exo+2 Gy X ray group was significantly decreased,and the apoptosis rate was significantly increased(P＜0.05).Conclusion UC-MSC-derived exosomes modified by miR-139-5p inhibit the stemness of MCF-7 cells and enhance the radiotherapy sen-sitivity of MCF-7 cells.

Objective:To explore the potential influencing factors of parenteral nutrition-associated cholestasis（PNAC）in extremely premature infants.Methods:A total of 83 cases of extremely premature infants who received parenteral nutrition and developed PNAC admitted to Shanxi Children's Hospital between October 2020 and October 2023 were selected as the case group，while 99 extremely premature infants who received parenteral nutrition but did not develop PNAC during the same period were selected as the control group. Basic information such as gender，gestational age，birth weight，and duration of parenteral nutrition were collected for the extremely premature infants. The health status of the infants at 1 minute and 5 minutes after birth was assessed using the Apgar standardized scoring method. One week after parenteral nutrition,platelet count(PLC)，mean platelet volume(MPV)，and platelet volume distribution width(PDW) were measured. Univariate analysis and non-conditional Logistic regression were used to analyze the potential influencing factors of PNAC in extremely premature infants after parenteral nutrition. Receiver operating characteristic(ROC) curves were plotted to evaluate the performance of the influencing factors and combined predictive factors in predicting PNAC in extremely premature infants receiving parenteral nutrition.Results:The 1-min and 5-min Apgar scores in the case group were lower than those in the control group( P<0.001);the percentages of gestational hypertension in mothers and postnatal infections in children were higher than those in the control group( P<0.05);and the duration of parenteral nutrition was longer than that in the control group( t=4.655, P<0.001), the differences were statistically significant. In the case group, after one week of parenteral nutrition,PLC was lower than that in the control group( t=4.949, P<0.001),MPV was higher than that in the control group( t=12.193, P<0.001), and PDW was higher than that in the control group( t=10.744, P<0.001), the differences were statistically significant.Multifactorial Logistic analysis showed that after adjusting for gender and gestational age，1-minute Apgar score（ OR=0.898），5-minute Apgar score（ OR=0.900），postnatal infection（ OR=1.256），duration of parenteral nutrition（ OR=1.426），one week after parenteral nutrition，PLC（ OR=0.902），MPV（ OR=1.441），and PDW（ OR=1.195）were independent influencing factors for PNAC in extremely premature infants（all P<0.05）. ROC curves showed that each factor and combined predictive factors had certain efficacy in predicting the occurrence of PNAC in extremely premature infants after parenteral nutrition. Conclusion:One-minute Apgar score,5-minute Apgar score，duration of parenteral nutrition，postnatal infection，one week after parenteral nutrition，the PLC,MPV and PDW are independent influencing factors for PNAC in extremely premature infants receiving parenteral nutrition.Each factor predicts the efficacy of parenteral nutrition for PNAC in extremely premature infants, and relevant factors should be controlled in time to reduce the incidence of PNAC in extremely premature infants.

A case of Sifrim-Hitz-Weiss syndrome(Sifrim-Hitz-Weiss syndrome,SIHIWES)is presented.The patient was a 35-year-old male with cryptorchidism,growth retardation,skeletal malformations,muscular atrophy,a wide forehead,special facial features like square face,small low-set and cup-shaped ears since birth.Whole-exon sequencing identified a heterozygous mutation(NM_001273:c.3047A>G(chr12-6701125)(p.K1016R))in CHD4 gene.The clinical significance of this mutation is currently unknown,and has not been previously reported.In light of the patient's symptoms,the case was diagnosed as Sifrim-Hitz-Weiss syndrome.This case represents the first instance of Sifrim-Hitz-Weiss syndrome in an adult patient in China.

Objective This study aimed to examine the risk factors and prognostic factors of brucellar spondylitis for early prevention and treatment of the disease,and improving the outcomes of patients.Methods A retrospective case-control study was conducted on the patients with brucellosis who were hospitalized in the Third Hospital of Hebei Medical University from June 2020 to June 2022.Patients were assigned to brucellosis without spondylitis group or brucellar spondylitis group according to the presence of spondylitis.The patients in brucellar spondylitis group were followed for 1 year.Then they were stratified into a subgroup of good or poor prognosis according to clinical outcomes.The dataset for the demographic and clinical variables of patients were analyzed using SPSS 26.0 software.Results A total of 300 patients with brucellosis were enrolled,including 113 cases of brucellosis without spondylitis and 187 cases of brucellar spondylitis.Multivariate analysis showed that age,time from onset to diagnosis,low back pain,and erythrocyte sedimentation rate were independent risk factors for brucellar spondylitis(P＜0.05).Of the 154 cases of brucellar spondylitis with known outcomes,121 cases showed good prognosis and 33 cases had poor prognosis.COX regression analysis showed that the time from onset to diagnosis,diabetes mellitus,paravertebral abscess,and neurological impairment were independent risk factors for poor prognosis in patients with brucellar spondylitis(P＜0.05).Conclusions Old age,prolonged time from onset to diagnosis,low back pain,and increased erythrocyte sedimentation rate are independent risk factors for spondylitis in patients with brucellosis.Prolonged time from onset to diagnosis,diabetes mellitus,paravertebral abscess,and neurological impairment are independent risk factors for poor prognosis of brucellar spondylitis.

Objective To investigate the quality of life of acute coronary syndrome patients(ACS)preoperatively to 6 months postoperatively percutaneous coronary intervention(PCI)and analyze its changing trend and influencing factors so as to provide reference for the improvement of ACS patients after PCI and direct for patient health management.Methods The patients with ACS were investigated for their sociodemographic characteristics,disease data,behavior and lifestyle and quality of life with the Seattle Angina Scale(SAQ)of PCI before PCI,1 month,3 months and 6 months after the surgery by means of medical records,face-to-face or telephone follow-up.Results A total of 235 ACS patients were surveyed before PCI,and 213(90.6％)of them who were successfully followed up to 6 months after PCI were included in this study,with a mean age of(62.67±9.18)years,and 76.1％being male.The results of the generalized estimation equation analysis showed that all the scores of the five dimensions of SAQ before PCI to 6 months after surgery,i.e.,physical limitation(Wald x2=83.118,P＜0.001),angina stabilizaton stability(Wald x2=289.369,P＜0.001),angina frequency(Wald x2=219.458,P＜0.001),treatment satisfaction(Wald x2=159.055,P＜0.001),and disease perception(Wald x2=130.839,P＜0.001)increased overall(all P＜0.001).However,the scores of physical limitation,angina stability and disease perception were only moderate at 6 months after surgery.The results of generalized linear model analysis showed that the factors affecting the quality of life before PCI to 6 months after PCI were gender,educational level,type of ACS,time to diagnosis,in-stent restenosis(ISR),tobacco smoking,and alcohol drinking.Conclusion The quality of life of the ACS patients gradually improved at 6 months after PCI,but the improvement effect of physical activity,angina stability and cognitive level was not ideal.Being female,low-level education,unstable angina,onset to diagnosis time 6 months or longer,occurrence of ISR,and postoperative tobacco smoking and alcohol drinking made patients have relatively low quality of life;therefore,more attention and guidance should be given to this group of population.

Ferroptosis is an iron-dependent cell death modality triggered by the accumulation of lipid peroxides and is closely linked to tumor pathogenesis. Ferritinophagy refers to the selective autophagic degradation of ferritin, releasing intracellular stored iron to maintain iron metabolic homeostasis. This process is also significantly associated with tumor-targeted interventions. This review systematically elucidates the mechanisms of ferroptosis and ferritinophagy, their roles in tumor progression, and the therapeutic potential of pharmacologically induced ferritinophagy in anticancer strategies.