ObjectiveTo investigate the repair effects of Zhengan Xifengtang on intestinal mucosal barrier in spontaneously hypertensive rats （SHRs） through the pathways of farnesoid X receptor （FXR）-myosin light chain kinase （MLCK）/phosphorylated myosin light chain （p-MLC） and its potential mechanism. MethodsForty 10-week-old male SHRs were randomly divided into model group， amlodipine besylate group （0.5 mg·kg^-1·d^-1）， and high， middle and low dose groups of Zhengan Xifengtang （34.5， 17.25， 8.625 g·kg^-1·d^-1）； eight age-matched male Wistar-Kyoto （WKY） rats of the same origin served as the normal control group. Drug intervention was carried out for 8 weeks， and the blood pressure of the rats was measured regularly. After the intervention， the rats were euthanized to collect tissue samples. Hematoxylin and eosin （HE） staining and Alcian blue-periodic acid-Schiff （AB-PAS） staining were used to evaluate the pathological morphology and the number of goblet cells in colonic mucosa. Enzyme-linked immunosorbent assay （ELISA） was employed to measure plasma lipopolysaccharide （LPS） and diamine oxidase （DAO） levels in each group of rats. Immunofluorescence （IF） assay was used to detect the relative fluorescence intensity of FXR and p-MLC in colonic tissue. Western blot was used to detect the zonula occludens-1 （ZO-1）， Occludin， Claudin-1， junctional adhesion molecule-1 （JAM-1）， mucin-2 （MUC2）， FXR， MLCK， and p-MLC protein expression in colon tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression levels of ZO-1， Occludin， Claudin-1， JAM-1， MUC2， FXR， MLCK， and MLC in colon tissue. ResultsCompared with the normal group， the blood pressure in the model group increased significantly （P<0.01）， the colonic mucosal structure was seriously damaged， and the number of goblet cells decreased significantly. The contents of LPS and DAO increased significantly （P<0.01）， the relative fluorescence intensity of FXR in colon decreased， while that of p-MLC increased （P<0.01）. The protein and mRNA expressions of ZO-1， Claudin-1， JAM-1， Occludin， MUC2 and FXR decreased significantly （P<0.01）， whereas the protein expression of MLCK and p-MLC increased significantly （P<0.01）. Additionally， the mRNA expression of MLCK and MLC increased significantly （P<0.01）. Compared with the model group， the Zhengan Xifengtang groups at various dosages and the amlodipine besylate group showed significantly reduced blood pressure （P<0.01）. The damage of colonic mucosa structure was alleviated， the infiltration of inflammatory cells decreased， and the number of goblet cells increased. LPS and DAO levels were decreased （P<0.05， P<0.01）. In the colon， the relative fluorescence intensity of FXR increased， while that of p-MLC decreased （P<0.05， P<0.01）. The protein and mRNA expression levels of ZO-1， Claudin-1， JAM-1， Occludin， and FXR increased significantly （P<0.05， P<0.01）， while the protein expression of MLCK and p-MLC decreased significantly （P<0.05， P<0.01）. Furthermore， the mRNA expression of MLCK and MLC decreased significantly （P<0.05， P<0.01）， and the protein expression of MUC2 increased significantly （P<0.05， P<0.01）. The expression of MUC2 mRNA in each dose group of Zhengan Xifengtang increased significantly （P<0.05， P<0.01）. ConclusionZhengan Xifengtang may regulate the FXR-MLCK/p-MLC signaling pathway and enhance the expression of tight junction protein， thereby reducing intestinal mucosal permeability， promoting mucosal barrier repair， decreasing LPS release into the blood， and ultimately lowering blood pressure.

ObjectiveTo investigate the repair effects of Zhengan Xifengtang on intestinal mucosal barrier in spontaneously hypertensive rats （SHRs） through the pathways of farnesoid X receptor （FXR）-myosin light chain kinase （MLCK）/phosphorylated myosin light chain （p-MLC） and its potential mechanism. MethodsForty 10-week-old male SHRs were randomly divided into model group， amlodipine besylate group （0.5 mg·kg^-1·d^-1）， and high， middle and low dose groups of Zhengan Xifengtang （34.5， 17.25， 8.625 g·kg^-1·d^-1）； eight age-matched male Wistar-Kyoto （WKY） rats of the same origin served as the normal control group. Drug intervention was carried out for 8 weeks， and the blood pressure of the rats was measured regularly. After the intervention， the rats were euthanized to collect tissue samples. Hematoxylin and eosin （HE） staining and Alcian blue-periodic acid-Schiff （AB-PAS） staining were used to evaluate the pathological morphology and the number of goblet cells in colonic mucosa. Enzyme-linked immunosorbent assay （ELISA） was employed to measure plasma lipopolysaccharide （LPS） and diamine oxidase （DAO） levels in each group of rats. Immunofluorescence （IF） assay was used to detect the relative fluorescence intensity of FXR and p-MLC in colonic tissue. Western blot was used to detect the zonula occludens-1 （ZO-1）， Occludin， Claudin-1， junctional adhesion molecule-1 （JAM-1）， mucin-2 （MUC2）， FXR， MLCK， and p-MLC protein expression in colon tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression levels of ZO-1， Occludin， Claudin-1， JAM-1， MUC2， FXR， MLCK， and MLC in colon tissue. ResultsCompared with the normal group， the blood pressure in the model group increased significantly （P<0.01）， the colonic mucosal structure was seriously damaged， and the number of goblet cells decreased significantly. The contents of LPS and DAO increased significantly （P<0.01）， the relative fluorescence intensity of FXR in colon decreased， while that of p-MLC increased （P<0.01）. The protein and mRNA expressions of ZO-1， Claudin-1， JAM-1， Occludin， MUC2 and FXR decreased significantly （P<0.01）， whereas the protein expression of MLCK and p-MLC increased significantly （P<0.01）. Additionally， the mRNA expression of MLCK and MLC increased significantly （P<0.01）. Compared with the model group， the Zhengan Xifengtang groups at various dosages and the amlodipine besylate group showed significantly reduced blood pressure （P<0.01）. The damage of colonic mucosa structure was alleviated， the infiltration of inflammatory cells decreased， and the number of goblet cells increased. LPS and DAO levels were decreased （P<0.05， P<0.01）. In the colon， the relative fluorescence intensity of FXR increased， while that of p-MLC decreased （P<0.05， P<0.01）. The protein and mRNA expression levels of ZO-1， Claudin-1， JAM-1， Occludin， and FXR increased significantly （P<0.05， P<0.01）， while the protein expression of MLCK and p-MLC decreased significantly （P<0.05， P<0.01）. Furthermore， the mRNA expression of MLCK and MLC decreased significantly （P<0.05， P<0.01）， and the protein expression of MUC2 increased significantly （P<0.05， P<0.01）. The expression of MUC2 mRNA in each dose group of Zhengan Xifengtang increased significantly （P<0.05， P<0.01）. ConclusionZhengan Xifengtang may regulate the FXR-MLCK/p-MLC signaling pathway and enhance the expression of tight junction protein， thereby reducing intestinal mucosal permeability， promoting mucosal barrier repair， decreasing LPS release into the blood， and ultimately lowering blood pressure.

Objective To investigate the effect of high,middle and low dose dexmedetomidine combined with sufentanil on perioperative analgesia and sleep quality in patients with oral cancer.Methods A total of 158 patients undergoing oral cancer surgery in the hospital from January 2023 to June 2024 were selected and divided into group A[n=53,0.6 μg/(kg h)dexmedetomidine+2 μg/kg sufentanil]and group B[n=53,0.4 μg/(kg h)dexmedetomidine+2 μg/kg sufentanil],Group C[n=52,0.2μg/(kg·h)dexmedetomidine+2 μg/kg sufentanil]by random number table method.Stress response indexes[brain-derived neurotrophic factor(BDNF),cortisol(Cor),interleukin-6(IL-6)],bifrequency index and analgcsia nociccption index(BIS,ANI),pain level,T lym-phocyte subsets CD3+,CD4+,CD8+levels,Richards Campbell Sleep Scale(RCSQ)score and adverse reactions were compared between the two groups.Results Compared with 12 h before surgery,serum levels of BDNF,Cor and IL-6 in 3 groups were decreased 48 h after surgery,group A was lower than group B,group C,group B was lower than group C(P＜0.05).Compared with T0,BIS at T1～T3 were significantly different between the 3 groups(P＜0.05),BIS at T1～T3 were lower than those at T0(P＜0.05),and there was no significant difference in BIS at the same time between the 3 groups(P＞0.05),from T,to T3,ANI was higher than that at T0,and ANI in group A was higher than that in group B and group C(P＜0.05).Compared with the preoperative results,the pain scores of the 3 groups were decreased at 1 h,6 h,24 h and 48 h after operation,and the pain scores of group A were lower than those of group B and C,and the pain scores of group B were lower than those of group C(P＜0.05).After operation,CD3+and CD4+were decreased in all 3 groups,group A was lower than group B and group C,group B was lower than group C(P＜0.05),and CD8+was increased in all 3 groups,group A was higher than group B and group C,group B was higher than group C(P＜0.05).Compared with 1 day before the operation,the sleep quality scores of the three groups on the night after the operation and the second night after the operation were all decreased,group A was lower than group B and group C,and group B was lower than group C(P＜0.05).The incidence of hypotension and sinus bradycardia in group A was higher than that in group B and group C(P＜0.05).There was no significant difference in the incidence of hypotension and sinus bradycardia between group B and group C(P＞0.05).There was no significant difference in the incidence of nausea,vomiting and dizziness among the three groups(P＞0.05).Conclusion The analgesic effect of 0.6 μg/(kg·h)dose dexmedetomidine com-bined with sufentanil can effectively reduce the body's stress response and immune suppression,improve sleep quality,but with a greater incidence of intraoperative hypotension and bradycardia.

Objective:To investigate the genetic causal relationship of leukocyte telomere length(LTL)with prostatitis,orchi-tis and epididymitis by two-sample Mendelian randomization(MR).Methods:Using LTL as the exposure factor and prostatitis,or-chitis and epididymitis as outcome factors,we mined the Database of Genome-Wide Association Studies(GWAS).Then,we analyzed the causal relationship of LTL with prostatitis,orchitis and epididymitis by Mendelian randomization using inverse variance weighting(IVW)as the main method and weighted median and MR-Egger regression as auxiliary methods,determined the horizontal multiplicity by MR-Egger intercept test,and conducted sensitivity analysis using the leaving-one-out method.Results:A total of 121 related sin-gle nucleotide polymorphisms(SNPs)were identified in this study.IVW showed LTL to be a risk factor for prostatitis(OR=1.383,95％CI:1.044-1.832,P=0.024),and for orchitis and epididymitis as well(OR=1.770,95％CI:1.275-2.456,P=0.000 6).Conclusion:Genetic evidence from Mendelian randomized analysis indicates that shortening of LTL reduces the risk of prostatitis,orchitis and epididymitis.

OBJECTIVES: To evaluate the application value of genetic newborn screening (gNBS) in the Yunnan region. METHODS: A prospective study was conducted with a random selection of 3 001 newborns born in the Yunnan region from February to December 2021. Traditional newborn screening (tNBS) was used to test biochemical indicators, and targeted next-generation sequencing was employed to screen 159 genes related to 156 diseases. Positive-screened newborns underwent validation and confirmation tests, and confirmed cases received standardized treatment and long-term follow-up. RESULTS: Among the 3 001 newborns, 166 (5.53%) were initially positive for genetic screening, and 1 435 (47.82%) were genetic carriers. The top ten genes with the highest variation frequency were GJB2 (21.29%), DUOX2 (7.27%), HBA (6.14%), GALC (3.63%), SLC12A3 (3.33%), HBB (3.03%), G6PD (2.94%), SLC25A13 (2.90%), PAH (2.73%), and UNC13D (2.68%). Among the initially positive newborns from tNBS and gNBS, 33 (1.10%) and 47 (1.57%) cases were confirmed, respectively. A total of 48 (1.60%) cases were confirmed using gNBS+tNBS. The receiver operating characteristic curve analysis demonstrated that the areas under the curve for tNBS, gNBS, and gNBS+tNBS in diagnosing diseases were 0.866, 0.982, and 0.968, respectively (P<0.05). DeLong's test showed that the area under the curve for gNBS and gNBS+tNBS was higher than that for tNBS (P<0.05). CONCLUSIONS gNBS can expand the range of disease detection, and its combined use with tNBS can significantly shorten diagnosis time, enabling early intervention and treatment.
Humans ; Infant, Newborn ; Neonatal Screening ; Genetic Testing ; Female ; Male ; Follow-Up Studies ; Prospective Studies ; China

Non-steroidal anti-inflammatory drugs(NSAIDs),commonly utilized analgesics,are extensively employed for managing pain associated with musculoskeletal disorders or injuries.Recent clinical studies have demonstrated a heightened risk of bone stress injuries(BSI)in soldiers and athletes,particularly during high-intensity training,due to NSAID usage.Furthermore,the impact of NSAIDs on fracture healing is well-documented;however,the precise mechanism by which their use during training contributes to an increased incidence of stress bone injuries remains unclear.This article aims to summarize potential mechanisms through an extensive review of domestic and international literature in order to standardize the utilization and clinical management of NSAIDs,optimize pain management strategies,and prevent stress bone injuries or fractures in specific populations such as soldiers and elite athletes.

Heat stroke is a heat-related illness caused by an imbalance between the body's heat production and heat dissipation,which could lead to multiple organ dysfunction syndrome with a high mortality rate.Rapid and effective reduction of core body temperature is key to successful treatment.This article reviews recent progress in the treatment of heat stroke,including new understandings of organ injury mechanisms,the timing,velocity and goals of cooling treatment,evaluation and selection of traditional cooling techniques(such as cold water immersion),and scientific evaluation of new cooling technologies(such as blood purification technology and intravascular heat exchange cooling technology),aiming to promote understanding and treatment of heat stroke.

Objective To investigate the postoperative efficacy of laparoscopic hiatal hernia repair(LHHR)combined with Toupet or Dor fundoplication for the treatment of esophageal hiatal hernia(HH).Methods A retrospective analysis was conducted on the case data of HH patients who underwent LHHR combined with Toupet(Toupet group,n=53)and Dor(Dor group,n=53)fundoplication between December 2018 and December 2022 in Department of General Surgery of Gansu Provincial Hospital.Intraoperative and postoperative recovery outcomes of both groups were observed.We analyzed and compared the incidence of dysphagia and gastroesophageal reflux disease questionnaire(GERD-Q)scores at preoperative and postoperative intervals of 1 month,6 months,and 1 year.The incidence of postoperative complications and the 1-year recurrence rate were compared between the two groups.Additionally,factors influencing postoperative dysphagia within the first month were examined.Results The differences between the two groups in operation time,intraoperative bleeding,postoperative ventilation time,postoperative extubation time and hospitalization time were not statistically significant(P>0.05).There was no significant difference in the incidence of immediate postoperative dysphagia in two groups(P>0.05).Furthermore,the differences between the two groups in the incidence of postoperative complications,such as bloating,abdominal pain and diarrhea,were not statistically significant(P>0.05).The incidence of dysphagia in Toupet group was higher than that in Dor group at 1 month postoperatively,and the difference was statistically significant(P=0.017);but the difference in the incidence of dysphagia between the two groups at 6 months and 1 year postoperatively was not statistically significant(P=0.767,1.000).The results of binary logistic regression analysis showed that both surgical procedure(OR=2.613,95%CI 1.141-5.983,P=0.023)and esophageal contractile reserve function(OR=2.921,95%CI 1.203-7.095,P=0.018)were independent risk factors for the incidence of dysphagia in patients with HH at 1 month after surgery.Compared with the preoperative period,the GERD-Q symptom scores were lower in both groups at 1 month,6 months,and 1 year postoperatively,and the difference was statistically significant(P<0.05);but there was no statistically significant difference between the groups at the same time point(Fintergroup=0.334,P=0.565).The difference between the two groups in 1-year postoperative recurrence rates was not statistically significant(P>0.05).Conclusions LHHR combined with Toupet or Dor fundoplication are both safe and effective surgical procedures for the treatment of HH,with excellent reflux control,fewer complications and lower recurrence rates,but Toupet fundoplication is more likely to have postoperative short-term dysphagia than Dor fundoplication.

Objective To analyze the impact of sarcopenia on the efficacy and adverse reactions of immunotherapy combined with chemotherapy in patients with advanced gastric cancer.Methods Patients with locally advanced or metastatic gastric cancer confirmed by pathology who were not eligible for radical surgery were selected as study subjects.A body composition analyzer was used to measure the appendicular muscle mass of the patients and calculate the skeletal muscle mass index(SMI).Based on the SMI,the patients were divided into sarcopenia group and non-sarcopenia group.On the basis of nutritional intervention and comprehensive exercise therapy,the patients were administered immu-notherapy combined with chemotherapy.The efficacy and adverse reactions were evaluated.The primary endpoint was progression-free survival(PFS),and the secondary endpoints were the objec-tive response rate(ORR)and treatment-related adverse reactions.Results A total of 52 gastric cancer patients were included,with 23 in the sarcopenia group and 29 in the non-sarcopenia group.The median PFS in the non-sarcopenia group was 9.8 months(95％CI,8.9 to 12.4),and was 5.4 months in the sarcopenia group(95％CI,4.9 to 8.1).The median PFS in the non-sarcopenia group was longer than that in the sarcopenia group,and the difference was statistically significant[HR(95％CI)=0.41(0.23 to 0.73),P=0.003].The results of the multivariate Cox propor-tional hazards regression model showed that comorbidities,treatment cycles,and sarcopenia were all independent prognostic factors affecting the PFS of gastric cancer patients(P＜0.05).The ORR in the non-sarcopenia group was 48.28％(14/29),and was 17.39％(4/23)in the sarcopenia group(x2=5.276,P＜0.05).Treatment-related adverse reactions with grading ≥3 in both groups were mainly hematological toxicities.In the non-sarcopenia group,the incidence of grading ≥ 3 treat-ment-related adverse reactions was 27.59％(8/29),and the incidence of grading＜3 treatment-re-lated adverse reactions(including those with no adverse reactions)was 72.41％(21/29).In the sarcopenia group,the incidence of grading ≥3 treatment-related adverse reactions was 56.52％(13/23),and the incidence of grading＜3 treatment-related adverse reactions(including those without adverse reactions)was 43.48％(10/23).The incidence of grading ≥3 treatment-related adverse reactions in the non-sarcopenia group was lower than that in the sarcopenia group(P=0.035).Conclusion For patients with locally advanced or metastatic gastric cancer complicated with sarcopenia,the median PFS of immunotherapy combined with chemotherapy is shorter,the ORR is lower,and the incidence of treatment-related adverse reactions is increased.Therefore,ear-ly intervention for sarcopenia should be implemented to improve the quality of life of patients with advanced gastric cancer.

OBJECTIVES: To assess the preliminary efficacy and safety of a dose-intensified C5VD regimen (cisplatin, 5-fluorouracil, vincristine, and doxorubicin) in children with locally advanced hepatoblastoma. METHODS: This prospective study enrolled 24 children with newly diagnosed, locally advanced hepatoblastoma who received the dose-intensified C5VD regimen at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children's Hospital between January 2020 and December 2023. Clinical characteristics, treatment outcomes, and chemotherapy-related toxicities were analyzed. RESULTS: Of the 24 patients, 13 were male and 11 were female, with a median age at diagnosis of 18.7 months (range: 3.5-79.4 months). All patients achieved complete macroscopic resection of hepatic lesions without liver transplantation. Serum alpha-fetoprotein levels decreased significantly after two chemotherapy cycles. During a median follow-up of 38.4 months (range: 15.8-50.7 months), all patients maintained continuous complete remission, with 3-year event-free survival and overall survival rates of 100%. Across 144 chemotherapy cycles, the incidence rates of grade 3-4 neutropenia, thrombocytopenia, and infections were 97%, 77%, and 71%, respectively; no treatment-related deaths occurred. Notably, 5 patients (21%) developed Brock grade ≥3 hearing loss, of whom 1 required a hearing aid. CONCLUSIONS The dose-intensified C5VD regimen demonstrates significant efficacy with an overall favorable safety profile in the treatment of newly diagnosed, locally advanced pediatric hepatoblastoma. Grade 3-4 myelosuppression and infection are the predominant toxicities. However, high‑dose cisplatin-induced ototoxicity remains a concern, highlighting the need for improved otoprotective strategies.
Humans ; Hepatoblastoma/pathology* ; Male ; Female ; Infant ; Liver Neoplasms/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child, Preschool ; Prospective Studies ; Doxorubicin/adverse effects* ; Child ; Cisplatin/adverse effects* ; Vincristine/adverse effects* ; Fluorouracil/adverse effects*