ObjectiveTo explore the target of Erzhiwan in reducing myocardial injury in ovariectomized mice through non-targeted myocardial metabolomics combined with experimental verification. MethodsOvariectomized mouse model was selected， 40 female C57BL/6 mice were randomly divided into sham operation group， model group， estrogen group（estradiol valerate， 1.3×10^-4 g·kg^-1）， Erzhiwan low and high dose groups（3.12， 9.36 g·kg^-1）， with 8 mice in each group. Each administration group was given the corresponding dose of Erzhiwan by gavage， and the sham operation group and model group were given equal volume of distilled water by gavage for 12 weeks. Echocardiography was used to detect cardiac function， hematoxylin-eosin（HE） staining was used to observe myocardial morphological changes， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of estrogen， N-terminal pro-brain natriuretic peptide（NT-proBNP）， hypersensitive troponin T（hs-TnT）， total cholesterol（TC）， triglyceride（TG）， low density lipoprotein cholesterol（LDL-C）， high density lipoprotein cholesterol（HDL-C）， interleukin（IL）-1β， IL-18 and tumor necrosis factor-α（TNF-α）. The non-targeted metabolomics of mouse myocardium were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， and the differential metabolites and corresponding metabolic pathways were obtained. The mRNA expression levels of phosphatidylinositol 3-kinase（PI3K） and protein kinase B（Akt） in mouse myocardial tissues were detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the protein expression levels of PI3K， Akt， phosphorylated（p）-Akt were detected by Western blot. ResultsCompared with the sham operation group， the model group showed abnormal cardiac function， increased myocardial fiber space， cardiomyocyte atrophy， sarcoplasmic aggregation， and occasional dissolution or rupture of muscle fiber， the level of estrogen in the serum was decreased， the levels of NT-proBNP， hs-TnT， IL-1β， IL-18， TNF-α， TG， TC and LDL-C were increased， and the level of HDL-C was decreased（P<0.01）. Compared with the model group， Erzhiwan could increase the level of estrogen， improve the abnormal cardiac function， reduce the pathological injury of myocardial tissue， decrease the levels of myocardial injury markers（NT-proBNP， hs-TnT） and inflammatory factors（IL-1β， IL-18， TNF-α）， decrease the levels of TG， TC， LDL-C， and increased the level of HDL-C（P<0.01）. The results of non-targeted myocardial metabolomics showed that 31 of the 162 differential metabolites between the model group and sham operation group were significantly adjusted after administration of Erzhiwan， which were mainly glycerol phospholipid metabolites. Pathway enrichment results showed that Erzhiwan mainly affected glycerophospholipid metabolic pathway， PI3K-Akt pathway， cyclic guanosine monophosphate（cGMP）-protein kinase G（PKG） pathway and other metabolic pathways. Compared with the sham operation group， the levels of phosphatidylcholine（PC， 11 types） and phosphatidylethanolamine（PE， 5 types） in mouse myocardial tissue of the model group were increased（P<0.05， P<0.01）， and the mRNA and protein expressions of PI3K and p-Akt were decreased（P<0.05， P<0.01）. Compared with the model group， the levels of PC（11 types） and PE（5 types） were decreased（P<0.05， P<0.01） in myocardial tissue of Erzhiwan group， the mRNA and protein expressions of PI3K and p-Akt were elevated（P<0.01）. ConclusionErzhiwan can alleviate the pathological injury of myocardium in ovariectomized mice， improve the abnormal cardiac function， improve lipid metabolism disorder， and reduce the levels of myocardial injury markers and inflammatory factors， which involves a number of signaling and metabolic pathways in the heart， among which glycerophospholipid metabolism pathway and PI3K/Akt pathway may have key roles.

Objective To explore the correlations of multimodal ultrasound manifestations of Hashimoto thyroiditis(HT)with normal thyroid function and serum thyroid peroxidase antibody(TPOAb)titer.Methods Data of gray-scale ultrasound,CDFI and shear wave elastography(SWE)of 100 HT patients with normal thyroid function were retrospectively analyzed.According to gray-scale ultrasound manifestations,HT was classified into focal type(type A),nodular-like type(type B),diffuse hypoechoic type(type C)and diffuse hyperechoic type(type D).Meanwhile,based on blood flow distribution shown on CDFI,HT was classified into abundant type,increased type,normal type and sparse type.Correlations of the mean Young's modulus(Emean)of thyroid gland and CDFI classification of HT with serum TPOAb titer were analyzed.Results For all 100 cases,serum TPOAb titer was(270.31±72.63)IU/ml.There were 38 cases of type A,26 cases of type B,20 cases of type C and 16 cases of type D based on gray-scale ultrasound,and 15 cases of abundant type,9 cases of increased type,69 cases of normal type and 7 cases of sparse type based on CDFI,respectively.The Emean of thyroid in all 100 cases was(22.31±7.38)kPa.Significant differences of serum TPOAb titer and thyroid Emean were found among different gray-scale ultrasound HT types(all P＜0.05).Thyroid Emean values of all 100 patients were positively correlated with TPOAb titer(rs=0.702,P=0.037).The thyroid Emean of patients with type A,B,C and D HT were positively correlated with TPOAb titer(rs=0.752,0.823,0.853,0.497,all P＜0.05),while the CDFI types of HT were negative correlated with serum TPOAb titer(rs=-0.746,P=0.035).Conclusion Both thyroid Emean and blood flow signals in HT patients with normal thyroid function were correlated with serum TPOAb titer.

Objective:To investigate the effect of mild moxibustion on transient receptor potential vanilloid type 1(TRPV1)channel expression in primary dysmenorrhea(PD)rats and explore its mechanism in alleviating central pain sensitization.Methods:Thirty-two female non-pregnant Wistar rats were randomized into a blank group,a model group,a mild moxibustion group,and a capsazepine group,with 8 rats in each group.Except for the blank group,the other three groups used estradiol benzoate,ice-water bath,and oxytocin to establish the rat PD model of cold-dampness stagnation pattern.The interventions began on day 1 of modeling,once a day,and lasted 10 d.The mild moxibustion group received mild moxibustion at Shenque(CV8)and Guanyuan(CV4),20 min/time;in the capsazepine group,capsazepine was injected at a dose of 2 mg/(kg·bw).The abdominal pain threshold was measured 10-30 min after oxytocin injection on day 11;enzyme-linked immunosorbent assay was used to detect serum prostaglandin F2α(PGF2α)level;the expression of TRPV1,cluster of differentiation 11B(CD11B),and proto-oncogene c-Fos in the spinal dorsal horn and hypothalamus was detected by immunofluorescence and Western blotting.Results:Compared to the blank group,the model group showed a decreased pain threshold(P<0.05)and an increased serum PGF2α level with elevated TRPV1,CD11B,and c-Fos protein expression in the spinal dorsal horn and hypothalamus(P<0.05).Compared to the model group,both the mild moxibustion group and capsazepine group showed significantly increased pain thresholds(P<0.05),along with decreased serum PGF2α levels and reduced protein expression levels of TRPV1,CD11B,and c-Fos in the spinal dorsal horn and hypothalamus(P<0.05).Rat pain threshold in the capsazepine group was higher than that in the mild moxibustion group(P<0.05).Serum PGF2α level,the expression levels of CD11B and c-Fos proteins in the spinal dorsal horn,as well as TRPV1,CD11B,and c-Fos proteins in the hypothalamus of the capsazepine group were lower than those in the mild moxibustion group(P<0.05).Conclusion:Mild moxibustion at Shenque(CV8)and Guanyuan(CV4)may alleviate the central pain sensitization in PD rats by down-regulating TRPV1 channel expression in the spinal dorsal horn and hypothalamus,thus playing an analgesic effect.

Objective To investigate the effects of indirect moxibustion on the expressions of DNA methyltransferases(DNMT)and methylation of the brain-derived neurotrophic factor(BDNF)promoter region in uterine tissues of rats with primary dysmenorrhea(PD);To explore the mechanism of epigenetic regulation of indirect moxibustion on PD model rats.Methods A total of 32 female SD rats were randomly divided into blank group,model group,indirect moxibustion group and Western medicine group,with 8 rats in each group.The PD model with cold dampness stagnation syndrome was established using ice-water baths combined with estradiol benzoate and oxytocin.Starting from the first day of modeling,the indirect moxibustion group received salt-partitioned moxibustion at"Shenque"and ginger-partitioned moxibustion at"Guanyuan"for 20 min,while the Western medicine group was gavaged ibuprofen solution.Both interventions were given once a day for 10 days.On day 11,writhing responses were observed and scored after oxytocin injection,Western blot and RT-qPCR were used to detect protein and mRNA expression of BDNF,DNMT3A and DNMT3B in uterine tissue,immunohistochemical staining was used to detect the positive expressions of DNMT3A and DNMT3B in uterine tissue.The DNA methylation of BDNF promoter region in uterine tissue was detected by sulfite sequencing.Results Compared with the blank group,the writhing latency was shortened and the writhing score increased in the model group(P<0.01);the protein and mRNA expressions of BDNF,DNMT3A and DNMT3B in uterine tissue increased(P<0.01),the positive expressions of DNMT3A and DNMT3B increased(P<0.01),and the DNA methylation rate in BDNF promoter region decreased(P<0.01).Compared with the model group,the writhing latency was lengthened and the writhing score decreased in the indirect moxibustion group and Western medicine group(P<0.05,P<0.01);the protein and mRNA expressions of BDNF,DNMT3A and DNMT3B in uterine tissue decreased(P<0.05,P<0.01),the positive expressions of DNMT3A and DNMT3B decreased(P<0.01),and the DNA methylation rate in BDNF promoter region increased(P<0.01).Conclusion Indirect moxibustion at"Shenque"and"Guanyuan"may inhibit the transcription of BDNF by increasing the DNA methylation level of BDNF promoter region,and reduce the expression of BDNF,so as to relieve the pain of PD rats.

Objective:To construct a questionnaire to measure parents′ behavioral and social drivers (BeSD) in administering rotavirus vaccine to their children, and to test the reliability and validity of the questionnaire.Methods:A questionnaire was constructed to investigate the BeSD of rotavirus vaccination among parents based on the WHO BeSD questionnaire. A survey was conducted among parents of children aged 0-3 years old in vaccination clinics from 15 community health service centers in Nanjing City of Jiangsu Province, Yuhuan and Kaihua Counties of Zhejiang Province, Anqing City of Anhui Province, and Yangpu District of Shanghai City from April to May in 2024. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to analyze the reliability (internal consistency reliability, combination reliability and split half reliability) and validity (structural validity, convergence validity and discriminative validity) of the questionnaire.Results:A total of 850 questionnaires were collected, of which 614 were valid, with an effective response rate of 72.20%. The EFA resulted in the refinement of the rotavirus vaccine BeSD questionnaire from 37 to 35 items (including 24 core items), and suggested a five-factor structure including the perceptions of vaccine, confidence in vaccine, social process of vaccination, motivation for vaccination, and practical problems of vaccination. The cumulative variance contribution rate reached 56.27%. The CFA confirmed an ideal five-factor model fit (GFI=0.82,CFI=0.86,PNFI=0.67,RMSEA=0.07). The AVE of each dimension was greater than 0.50. The AVE square root of each dimension of the questionnaire was greater than its correlation coefficient. The Cronbach′s α coefficient of the total questionnaire was 0.79.Conclusion:The developed BeSD questionnaire of rotavirus vaccine has good reliability and validity, and can be used to measure parents′ behavioral and social factors in administering rotavirus vaccine to their children.

Objective To investigate the biomechanical differences in plantar pressure,postural stability,and plantar Visual Analogue Scale(VAS)scores between normal feet and unilateral/bilat-eral pes cavus,reveal their unique neuromechanical compensation mechanisms,and construct a sta-bility early warning model based on the minimum center of pressure(COP)trajectory classification.Methods A total of 70 patients with pes cavus from December 2023 to October 2024 were selected as study subjects,including 33 patients in the unilateral pes cavus group and 37 patients in the bilat-eral pes cavus group.During the same period,32 normal feet were included as normal foot group.A flat-panel plantar pressure testing system was used to collect dynamic plantar pressure data and COP trajectories from three groups at a self-selected walking speed.There were no statistically significant differences in baseline data such as age,gender,and body mass index among the three groups(P＞0.05).One-way analysis of variance and the Wilcoxon rank-sum test were used to compare the differences in maximum pressure,contact area,VAS scores,and the 95％confidence ellipse area of the COP among the three groups in 10 plantar regions.Results Patients with pes cavus exhibited lower peak pressure in the MF region compared to normal feet,while higher peak pressure in the M2,M3,and MH regions.Patients with bilateral pes cavus showed lower peak pressure in the T1 region compared to normal feet,and patients with unilateral pes cavus had lower peak pressure in the LH region compared to the normal group(P＜0.05).The plantar contact area in patients with pes cavus was reduced in the T1,M2,M3,M4,MF,and MH regions compared to normal feet(P＜0.05).The 95％confidence ellipse area of the COP was larger in both the bilateral and uni-lateral pes cavus groups compared to the normal foot group(P＜0.001).Unilateral pes cavus pres-ented a specific lateral COP drift(amplitude of 3 to 4 cm),which is a biomechanical manifestation of compensatory eversion of the unaffected foot.Patients with bilateral pes cavus exhibited a"bimod-al oscillation"trajectory(amplitude of 6 to 8 cm),suggesting possible vestibular-spinal regulatory dysfunction and the poorest postural stability.In the pes cavus group,there was a significant in-crease in pressure in the M2,M3,and MH regions,with peak pressures exceeding 190 kPa in pa-tients with bilateral pes cavus,which was highly correlated with plantar pain and could serve as a pain early warning threshold.Conclusion Unilateral and bilateral pes cavus exhibit significantly different neuromechanical compensation patterns.The classification based on the"lateral drift"and"bimodal oscillation"characteristics of the COP trajectory can serve as a stability early warning indi-cator for assessing fall risk.Decompression interventions targeting the key pressure regions of M2,M3,and MH(such as customized orthotic insoles)are the core strategies for alleviating pain and optimizing dynamic gait stability.

Objective:This study aimed to investigate the correlation between the ingested dose of amlodipine and the severity of shock in affected patients by analyzing clinical data from documented cases.Methods:This study respectively included adult patients treated for amlodipine poisoning-induced shock at the emergency department of Peking University Third Hospital between January 2018 and December 2022. Additionally, cases reported in the literature from January 1997 to December 2022 were also included. Patients were categorized into two groups: non-refractory shock and refractory shock. Statistical analysis was conducted on the data between the two groups.Results:This study included a total of 80 patients, with 37 experiencing non-refractory shock patients and 43 presenting with refractory shock patients. Significant differences were observed between the two groups in terms of sex distribution ( P=0.037) and the ingested amlodipine dose ( P=0.001). Through binary logistic regression analysis, the amlodipine dose was identified as an independent predictor of shock severity ( OR=1.43, 95% CI: 1.12-1.84, P=0.005). A subgroup analysis was performed on patients who were poisoned by ingesting amlodipine alone, further confirming the significant dose difference ( P=0.003) between the non-refractory shock and refractory shock categories. The area under the receiver operating characteristic curve (AUC) for predicting refractory shock in patients with amlodipine poisoning was 0.723 (95% CI: 0.613-0.833). The optimal cutoff dose for predicting refractory shock was 347.5 mg, with a sensitivity of 0.651 and a specificity of 0.784. Sensitivity analyses, excluding cases of mixed poisoning, yielded a higher AUC of 0.795 (95% CI: 0.634-0.956), with a slightly adjusted cutoff dose of 350 mg, a sensitivity of 0.867, and a specificity of 0.737. The dose-response relationship table between medication dosage and incidence of refractory shock shows that as the dosage increases, the proportion of refractory shock also increases. Conclusions:In adult patients with amlodipine poisoning, the severity of shock was correlated with the ingested dose of the drug. When the ingested amlodipine dose exceeds 347.5 mg, it is crucial to be cautious of the development of refractory shock.

Objective To investigate the potential role of plasma adiponectin concentration in predicting the response of patients with depression to electroconvulsive therapy(ECT).Methods This study enrolled depressive patients scheduled for ECT at the First Hospital of Shanxi Medical University between January 2022 and March 2024.Patients were categorized as either ECT responders(>50%reduction)or non-responders(≤50%reduction)based on post-ECT reduction rate of the 24-item Hamilton depression scale(HAMD)scores from baseline.Plasma adiponectin levels were measured in all patients before their first ECT treatment.To identify predictors of ECT response in patients with depression,the predictive value of plasma adiponectin was evaluated using receiver operating characteristic(ROC)curve analysis.Results A total of 80 patients with depression were enrolled including 44 in the ECT-responsive group and 36 in the non-responsive group.The plasma adiponectin level was significantly higher in the responsive group than in the non-responsive group[5.67(3.64,10.55)μg/mL vs.4.01(2.59,5.04)μg/mL,P=0.002].Pearson correlation analysis revealed a significant positive correlation between plasma adiponectin levels and the HAMD reduction rate(r=0.300,P=0.007).Multivariate logistic regression analysis showed that plasma adiponectin was independently associated with the response to ECT in patients with depression(OR=1.218,95%CI:1.009-1.470,P=0.040).Furthermore,ROC curve analysis demonstrated that the area under the curve(AUC)for adiponectin in predicting ECT response was 0.748(95%CI:0.583-0.813).Conclusion Pretreatment plasma adiponectin may serve as a potential biomarker for predicting response to ECT in patients with depression.

Objective To study the relationship between the expression of long non-coding RNA lung adenocarcinoma metastasis-associated transcript 1(lncRNA MALAT1)and microRNA(miR)-181a-5p in lung adenocarcinoma tissues and the signal pathway of Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3),clinicopathological features and prognosis.Methods 218 patients with lung adenocarcinoma who had surgical resection at our institution between January 2018 and May 2021 had their cancer tissues and nearby normal lung tissues collected,the levels of lncRNA MALAT1,miR-181a-5p and key factors of JAK2/STAT3 signaling pathway(JAK2 mRNA,STAT3 mRNA)in lung adenocarcinoma tissues and adjacent tissues were detected by reverse transcription polymerase chain reaction(RT-PCR).The correlation between the expression levels of lncRNA MALAT1 and miR-181a-5p in cancer tissues of lung adenocarcinoma patients and the levels of key factors in JAK2/STAT3 signaling pathway were analyzed by Pearson test.The relationship between the expression levels of lncRNA MALAT1 and miR-181a-5p and the clinicopathological features of lung adenocarcinoma patients were analyzed.Patients with lung adenocarcinoma were followed up for 3 years,and their prognosis was counted,the 3-year overall survival rate of lncRNA MALAT1 and miR-181a-5p low/high expression groups were analyzed by Kaplan-Meier method.The prognostic factors were analyzed by univariate and multivariate COX risk proportional regression models.Results In lung adenocarcinoma tissues,the expression levels of lncRNA MALAT1,JAK2,and STAT3 mRNA were substantially greater(P＜0.05)than in neighboring normal lung tissues,whereas the expression level of miR-181a-5p was significantly lower(P＜0.05)in compared to nearby normal lung tissues.Pearson test results showed that,lncRNA MALAT1 was positively correlated with JAK2 and STAT3 mRNA expression levels in cancer tissues of patients with lung adenocarcinoma(P＜0.05,r=0.526、0.483),and miR-181a-5p was negatively correlated with JAK2 and STAT3 mRNA expression levels in cancer tissues of patients with lung adenocarcinoma(P＜0.05,r=-0.430、-0.493).lncRNA MALAT1 had a considerably greater expression rate and miR-181a-5p had a significantly lower expression rate in patients with TNM stage Ⅲa,lymph node metastasis and poorly differentiated lung adenocarcinoma than in patients with TNM stage Ⅰ-Ⅱ,without lymph node metastasis and moderately well differentiated lung adenocarcinoma(P＜0.05).Three patients were lost during the 3-year follow-up of 218 patients with lung adenocarcinoma,and the 3-year overall survival rate was 58.14％(125/215).The 3-year overall survival rate of the lncRNA MALAT1 high expression group was considerably lower than that of the lncRNA MALAT1 low expression group.The miR-181a-5p high expression group had a substantially greater(P＜0.05).Lymph node metastasis,TNM stage Ⅲ a,decreased expression level of miR-181a-5p,and increased expression level of lncRNA MALAT1 are risk factors for the prognosis of patients with lung adenocarcinoma(P＜0.05).Conclusion The low expression of miR-181a-5p and the high expression of lncRNA MALAT1 in lung adenocarcinoma tissues are related to TNM stage Ⅲa,lymph node metastasis and poor prognosis,which may promote the progression of lung adenocarcinoma and cause poor prognosis by activating JAK2/STAT3 signaling pathway.

Objective:To investigate the therapeutic efficacy and safety of tislelizumab combined with platinum-based drugs in patients with advanced non-small cell lung cancer (NSCLC).Methods:A prospective randomized controlled study was conducted. Eighty-six patients with clinical stage Ⅳ NSCLC in Huaibei People's Hospital from June 2020 to June 2023 were selected as the study subjects, and the patients were divided into the control group and the observation group based on the randomized numerical table method, with 43 cases in each group. The control group was treated with platinum-based drugs, the observation group was treated with platinum-based drugs combined with tislelizumab, and all patients were treated for 4-6 cycles. The two groups were compared in terms of therapeutic efficacy, serum tumor markers [carcinoembryonic antigen (CEA), cytokeratin 19 soluble fragment (CYFRA21-1) and carbohydrate antigen 125 (CA125)] detected by chemiluminescence method, serum immune function indicators [CD3 +, CD4 +, CD8 + cell ratios and CD4 + cell number-to-CD8 + cell number ratio (CD4 +/CD8 +)] detected by flow cytometry, and quality of life [European Organization for Research and Treatment of Cancer (EORTC) quality of life measurement scale (QLQ-C30) scores in functional domain and symptom domain], and incidence of adverse reactions. Results:The differences in baseline data of age, gender, degree of tumor differentiation, pathological type, lesion location, programmed death receptor ligand 1 expression between the observation group and the control group were not statistically significant (all P > 0.05). After treatment, the objective remission rates in the observation and control groups were 34.9% (15/43) and 18.6% (8/43), respectively, and the difference was not statistically significant ( χ2 = 2.91, P = 0.088); the disease control rate in the observation group was 74.4% (32/43), which was higher than that in the control group [51.2% (22/43)], and the difference was statistically significant ( χ2 = 4.98, P = 0.026). The differences in the serum levels of CEA, CYFRA21-1 and CA125 between the observation group and the control group before treatment were not statistically significant (all P > 0.05); the serum levels of CEA, CYFRA21-1 and CA125 in the observation group were lower than those in the control group after treatment, and the differences were all statistically significant (all P < 0.01). The differences in the CD3 +, CD4 +, CD8 + cell ratios and CD4 +/CD8 + between the observation group and the control group before treatment were not statistically significant (all P > 0.05); the CD3 +, CD4 + cell ratios and CD4 +/CD8 + in the observation group were higher than those in the control group, the CD8 + cell ratio was lower than that in the control group after treatment, and the differences were all statistically significant (all P < 0.01). Before treatment, there were no statistically significant differences in the scores of EORTC QLQ-C30 functional domain and symptom domain between the observation group and the control group (both P > 0.05); after treatment, the functional domain score of the observation group was higher than that of the control group, the symptom domain score was lower than that of the control group, and the differences were statistically significant (both P < 0.01). The incidence rates of skin itching, rash and diarrhea in the observation group were 23.3% (10/43), 20.9% (9/43) and 48.8% (21/43), respectively, which were higher than those in the control group [4.7% (2/43), 2.3% (1/43) and 27.9% (12/43)], and the differences were statistically significant (all P < 0.05). Conclusions:Tislelizumab combined with platinum-based drugs in advanced NSCLC patients can enhance the short-term efficacy, reduce serum tumor marker levels, and improve the immune function and quality of life of the patients, but it will increase the occurrence of skin and digestive tract adverse reactions.