Objective To observe the effect of Zhibo Dihuang Pill(ZDP) on leptin-induced idiopathic central precocious puberty(ICPP) in mice.Methods Eighteen BALB/c female mice aged 18 months were randomized into 6 groups: normal group,model group,high-and low-dose ZDP groups(at the dose of 101.4 and 50.7 g?kg-1?d-1 respectively),and megestrol acetate(3.9 mg?kg-1?d-1)group and gonadotropin releasing hormone analogues(GnRH-A) group(at the first dose of 1573.5 ?g/kg,the second and the third dose of 1180 ?g/kg,once every other day).Except the normal group,the mice in other groups received intraperitoneal injection of leptin 20mg/kg to establish ICPP model.After treatment,the vaginal opening,body weight,uterus weight and ovaries weight as well as the serum levels of luteinizing hormone(LH),estrogen(E2) were detected.Meanwhile,the uterus index and ovaries index were also examined.Results High-dose ZDP had an inhibition on the advance of vaginal opening induced by leptin after modeling for 4~6 days(P0.05).Conclusion The therapeutic effect of ZDP for ICPP is probably related with the inhibition of the advance of hypothalamic-pituitary-gonad axis activation.

Chronic myeloid leukemia (CML) is a malignant tumor formed by clonal proliferation of bone marrow hematopoietic stem cells. With the improvement of disease awareness and the introduction of new drugs, more than 90% of CML patients can achieve long-term survival. However, a few patients still show drug resistance. This article reviews the mechanism of drug resistance in CML patients treated with tyrosine kinase inhibitor (TKI) and the characteristics of ABL kinase region mutation.

Objective To compare the curative efficacy of conventional transcatheter arterial chemoembolization(C-TACE)and drug-eluting bead transcatheter arterial chemoembolization(D-TACE)combined with local thermal ablation in the treatment of massive hepatocellular carcinoma(HCC).Methods A total of 72 patients with massive HCC,who were admitted to the Nanyang Municipal First People's Hospital of China from April 2018 to June 2021,were enrolled in this study.By using random number table method,the patients were divided into study group(n=36)and control group(n=36).The patients of the control group were treated with local thermal ablation combined with C-TACE,while the patients of study group were treated with local thermal ablation combined with D-TACE.The clinical efficacy,tumor markers,liver function,serological indicators,blood perfusion indexes,and adverse reactions were compared between the two groups.All patients were followed up for two years.The progression-free survival(PFS)were compared between the two groups.Results The disease control rate(DCR)and objective response rate(ORR)in the study group were higher than those in the control group(P＜0.05).At 3 months after operation,the levels of alpha-fetoprotein(AFP)and prothrombin induced by Vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ)were decreased in both groups(P＜0.05),which in the study group were obviously lower than those in the control group(P＜0.05);the alanine aminotransferase(ALT)level was increased in both groups,which in study group was lower than that in the control group(P＜0.05);the albumin(ALB)level was decreased in both groups(P＜0.05),which in the study group was higher than that in the control group(P＜0.05);the epidermal growth factor receptor(EGFR),vascular endothelial growth factor(VEGF)and thymokinase 1(TK1)levels were decreased in both groups(P＜0.05),which in the study group were lower than those in the control group;the blood volume(BV)and blood flow(BF)were decreased in both groups(P＜0.05),which in the study group was lower than those in the control group;the mean transit time(MTT)of contrast agent was increased in both groups(P＜0.05),which in the study group was higher than that in the control group.During the follow-up of two years,one patient in each group was lost in touch,the follow-up success rate was 97.22％.The median PFS in the study group and the control group was 15.41 months(95％CI:7.02-23.19)and 12.34 months(95％CI:6.16-22.30)respectively.The PFS curve of the study group was better than that of the control group(P＜0.05).Conclusion Local thermal ablation combined with D-TACE can improve liver function and blood perfusion in patients with massive HCC,with a remarkable clinical efficacy.This therapy can reduce tumor markers levels,regulate serum EGFR,VEGF and TK1 expressions,and prolong the median PFS,besides,it is clinically safe and reliable.

Objective:To investigate the clinical characteristics and prognosis of acute myeloid leukemia (AML) patients with positive TLS-ERG fusion gene.Methods:The clinical data of 9 AML patients with positive TLS-ERG fusion gene in the First Hospital of Jilin University from June 2013 to August 2020 were retrospectively analyzed, and the relevant literature was reviewed.Results:Among 9 patients with positive TLS-ERG fusion gene, there were 5 males and 4 females, with a median age of 16 years old (6-40 years old). Five patients received chemotherapy alone, 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and 1 patient did not receive systematic treatment. Among 8 patients with systematic treatment, 1 patient had complete remission after the first induction chemotherapy and 5 patients had complete remission after induction therapy. The median overall survival time of 5 patients with chemotherapy alone was 1.5 months (1-11 months), of which 3 patients did not respond to the first course of treatment and died of infection, and 2 patients died after relapse. The median overall survival time of 3 patients with allo-HSCT was 16 months (13-17 months), of which 2 patients died after relapse and 1 patient had sustained molecular complete remission by the end of follow-up.Conclusions:AML with positive TLS-ERG fusion gene has low incidence rate and poor induction efficacy. Hematopoietic stem cell transplantation may partially improve the survival prognosis of patients, but it cannot overcome the adverse effect of positive TLS-ERG fusion gene on prognosis.

Objective:To investigate the effects of Apelin-13 regulatory peptide on neuronal cell pyroptosis in mice modeled with cerebral ischemia-reperfusion(I/R).Methods:We prepared a mouse cerebral I/R model using middle cerebral artery embolization and Reperfusion(MCAO/R).The HT22 cell injury model was prepared by the oxygen glu-cose deprivation/reoxygenation(OGD/R),and Apelin-13 treatment was also given.Neurological function was assessed by neurological deficit score;hematoxylin-eosin(HE)staining and Nissl staining were used to observe the morphologic changes of the infarcted area of the mice;and 2,3,5triphenyltetrazolium chloride(TTC)staining was used to observe the volume of cerebral infarcts;The expression of NOD-like receptor thermoprotein structural domain-related protein 3(NLRP3),gasdermin D(GSDMD),caspase-1,apoptosis-associated speck-like protein(ASC),interleukin 1β(IL-1β),and interleukin 18(IL-18)in brain tissues from infarcted areas or HT22 cells was detected by Western Blot,and IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay(ELISA)in serum of mice and culture supema-tants;The cell viability and cell damage of HT22 were detected by CCK-8 kit and lactate dehydrogenase(LDH)assay kit,respectively;caspase-1 activity was measured by caspase-1 activity kit in HT22 cells;and the expression of caspase-1 and GSDMD was observed by immunofluorescence staining in HT22 cells.Results:Apelin-13 significantly improved neurological function and cerebral infarct volume in I/R mice,and attenuated pathological damage in the in-farcted area.It also reduced the serum levels of IL-1β and IL-18.In addition,Apelin-13 reduced the expression of mol-ecules such as NLRP3,GSDMD,caspase-1,IL-1β,and IL-18 in the cerebral infarct area of mice.In vitro experiments showed that Apelin-13 significantly increased the viability of OGD/R-treated HT22 cells,decreased caspase-1 activity,and reduced the LDH content,as well as decreased the expression of molecules such as NLRP3,GSDMD,caspase-1,IL-1β,IL-18,and so on,in OGD/R-treated HT22 cells.Conclusion:Apelin-13 inhibits pyroptosis through the NL-RP3/caspase-1/GSDMD pathway in cerebral ischemia/reperfusion mice and thus exerts neuroprotective effects.

Objective To explore the feasibility of quantitative EEG parameters for prognostic prediction of patients with severe aneurysmal subarachnoid hemorrhage(SaSAH)90 d after the onset of the disease.Methods Patients with SaSAH admitted to the Neurosurgical Intensive Care Unit(NSICU)of Henan Provincial People's Hospital from September 2022 to September 2023 were prospectively consecutively enrolled,and baseline data were collected,including age,gender,medical history(hypertension,diabetes mellitus,coronary artery disease,and stroke),history of smoking,history of drinking,location of aneurysm(anterior circulation,posterior circulation),surgical modality(craniotomy,interventional surgery,hybrid surgery),Hunt-Hess classification,Glasgow coma scale(GCS)score,acute physiology and chronic health status scoring system Ⅱ(APACHE Ⅱ)score,subarachnoid hemorrhage early brain edema score(SEBES),first randomized blood glucose level after admission to NSICU,lactate level,and duration of NSICU stay.Quantitative EEG monitoring was performed in all patients within 48 h after admission to the NSICU,and amplitude-integrated electroencephalogram(aEEG)upper and lower boundaries,95％spectral edge frequency(SEF95),α change,(δ+θ)to(α+β)power ratio(DTABR),brain symmetry index(BSI),and spectral entropy were collected.Based on modified Rankin scale(mRS)scores 90 d after onset,patients were categorized into good prognosis(mRS score 2 points)and poor prognosis(mRS score 3-6 points)groups.Spearman rank correlation was used to analyze the correlation between quantitative EEG parameters and mRS scores in SaSAH patients.Multifactorial Logistic regression analysis was used to screen for correlates of poor prognosis,and receiver operating characteristic(ROC)curves were plotted to evaluate the efficacy of each index in predicting patients'poor prognosis.Results(1)A total of 72 patients with SaSAH were included,with 47 in the poor prognosis group and 25 in the good prognosis group,and the poor prognosis rate at 90 d after the onset was 65.3％.There was no statistically significant difference between the two groups in terms of gender,age,hypertension,diabetes mellitus,coronary artery disease,history of stroke,history of smoking,history of drinking,location of aneurysm,surgical modality,lactate level,and length of hospitalization in the NSICU(all P＞0.05);the differences between the Hunt-Hess grading,SEBES,and random blood glucose were statistically significant upon comparison(all P＜0.05).Compared with the good prognosis group,the changes of aEEG upper and lower boundary,SEF95,α change and spectral entropy were lower in the poor prognosis group,but DTABR and BSI were higher(all P＜0.05).(2)Spearman rank correlation analysis showed that the upper border of aEEG(r=-0.41,P＜0.01),lower border of aEEG(r=-0.54,P＜0.01),SEF95(r=-0.46,P＜0.01),α change(r=-0.53,P＜0.01)and spectral entropy(r=-0.39,P＜0.01)were negatively correlated with the mRS scores of SaSAH patients,and DTABR(r=0.52,P＜0.01)and BSI(r=0.33,P＜0.01)were positively correlated with poor prognosis of SaSAH patients.(3)The results of multifactorial Logistic regression analysis showed that Hunt-Hess grading(level Ⅳ vs.Ⅲ:OR,1.203,95％CI 1.005-1.441,P=0.044;level V vs.Ⅲ:OR,1.661,95％CI 1.109-2.487,P=0.014),SEBES(OR,1.647,95％CI 1.050-2.586;P=0.030),aEEG lower border(OR,0.687,95％CI 0.496-0.953l;P=0.024),SEF95(OR,0.436,95％CI0.202-0.937;P=0.034),α change(OR,0.368,95％CI0.189-0.717;P=0.003),DTABR(OR,1.324,95％CI 1.064-1.649;P=0.012),and BSI(OR,1.513,95％CI 1.026-2.231;P=0.036)were influencing factors of poor prognosis in SaSAH patients.ROC curve analysis showed that all of the above seven indicators had a certain predictive value for poor prognosis in SaSAH patients,among which the area under the curve of DTABR was the highest as 0.862(95％CI 0.761-0.932),with sensitivity 85.11％and specificity 80.00％.Conclusion Quantitative EEG parameters aEEG lower border,SEF95,α change,DTABR,and BSI may have certain predictive value for the short-term prognosis of SaSAH patients,which needs to be further confirmed in future multi-center large-sample studies.

Objective:To explore the promoted role of calcium-sensing receptor (CaSR) overexpression in proliferation and differentiation of immature white matter progenitor cells after ischemia in vitro. Methods:Periventricular white matter cells from 5-d-old rats were cultured in vitro and divided into control group, oxygen-glucose deprivation (OGD) group, OGD+gadolinium chloride (GdCl 3) group, and OGD+ CaSR silenced group. CaSR expression was agitated by GdCl 3, and CaSR gene expression was inhibited by gene silencing. CaSR mRNA levels 24, 48 and 72 h, and 7 and 14 d after OGD were detected by real-time fluorescence quantification-PCR (RT-qPCR); cell proliferation 48 h after OGD was detected by inverted microscope, and cell differentiation 24, 48, and 72 h, and 7 and 14 d was detected by double immunofluorescence staining. Results:(1) CaSR mRNA expressions: CaSR mRNA expressions in OGD group 48 and 72 h and 7 d after OGD were statistically higher than those in control group ( P<0.05). Forty-eight and 72 h, and 7 and 14 d after OGD, CaSR mRNA expressions in OGD+GDCL 3 group were statistically higher than those in control group and OGD group ( P<0.05); the CaSR mRNA expressions in the OGD+CaSR silenced group were significantly lower than those in the control group ( P<0.05). (2) Cell proliferation and differentiation: 48 h after OGD, the cell sphere diameter of OGD group ([75.26±26.07] μm) was significantly increased as compared with that of control group ([57.96±18.92] μm, P<0.05); the cell sphere diameter of OGD+GdCl 3 group ([91.92±21.82] μm) was significantly increased as compared with that of control group and OGD group ( P<0.05); and the cell sphere diameter of OGD+ CaSR silenced group ([24.09±8.34] μm) was significantly shorter than that of control group and OGD group ( P<0.05). At 48 and 72 h after OGD, the number of O4 +/CaSR + olidoendrocyte precursor cells (OPCs) in OGD group was significantly larger than that in control group, that in OGD+GdCl 3 group was significantly larger than that in control group and OGD group, and that in OGD+ CaSR silenced group was significantly smaller than that in control group and OGD group ( P<0.05). Conclusion:CaSR overexpression could promote the proliferation and differentiation of progenitor cells to OPCs.

Objective:To explore the effect of empowerment education in patients with coronary heart disease after percutaneous coronary intervention (PCI) .Methods:From June 2020 to July 2021, convenience sampling was used to select 90 patients with coronary heart disease who received PCI in the Department of Cardiology of Qinhuai Medical District, Eastern Theater Command General Hospital as the research object. The 45 patients admitted from June to December 2020 were set as the control group, and the 45 patients admitted from January to July 2021 were set as the observation group. The control group received routine health education, and the observation group was given empowerment education on this basis. The physical activity level and aerobic exercise endurance of the two groups of patients were compared.Results:Repeated measures analysis of variance showed that there were between-group, time and interaction effects in the 6-minute walking distance between the two groups before intervention, one month and three months after intervention, and the differences were statistically significant ( P<0.05) . The physical activity levels of patients in the observation group were higher than those in the control group after one and three months of intervention, and the differences were statistically significant ( P<0.05) . Conclusions:Empowerment education can improve physical activity level and aerobic exercise endurance in patients with coronary heart disease after PCI.

Objective:To explore the correlation between the index of hemodynamics in perinatal period and retinopathy of prematurity(ROP), so as to provide basis for the better prevention and treatment of ROP.Methods:From May 2017 to April 2019, the preterm infants were admitted to the Neonatal Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University at birth and were hospitalized for more than 2 weeks, gestational age ≤ 35 weeks and birth weight ≤ 2 500 g. They were selected as the study objects.The perinatal data including heart rate, blood pressure, patent ductus arteriosus, ventricular septal defect, and NT-proBNP level on the 1 st, 7 th and 14 th day, respectively after birth were collected.They were divided into ROP group and non ROP group according to the results of the retinopathy screening report.The influencing factors of ROP were screened out by univariate analysis and multivariate regression analysis. Results:A total of 1 119 subjects were included, 105 infants with ROP were detected, and the prevalence of ROP was 9.4%.Among them, 12 cases of pre-threshold lesion type 1 and threshold lesions required treatment, accoun-ting for 1.07% of screened preterm infants .Univariate analysis and multivariate regression analysis revealed that gestational age, birth weight, total oxygen therapy time, and intrauterine growth restriction were all factors affecting ROP, and 2 hemodynamic related indicators, such as the level of NT-proBNP in plasma on the 14 th day after birth, and placenta previa or abruption were also related to ROP( OR=0.604, 0.647, 1.276, 2.361, 1.688 and 2.506, respectively, all P<0.05). Conclusion:The hemodynamic changes in perinatal period may be involved in the formation of ROP, and it is necessary to further clarify its mechanism.

Objective To investigate the relationship and potential pathways between metal(loid)exposure and the risk of polycystic ovary syndrome(PCOS)in women of childbearing age. Methods This case-control study included 200 patients with PCOS(cases)and 896 non-PCOS controls with the age of 25-37 years.The concentrations of 29 metal(loid)s in the follicular fluid(FF)and clinical indicators in the serum were measured in all participants.Logistic regression analysis and mediation analysis were conducted to evaluate the associations between metal(loid)exposure and PCOS risk and investigate the possible roles of clinical indicators,respectively. Results Logistic regression analysis revealed an association between high copper levels in FF and increased PCOS risk(highest vs.lowest quartile:adjusted odds ratio=2.94,95%confidence interval:1.83-4.72).A high luteinizing hormone/follicle-stimulating hormone ratio and elevated levels of testosterone and anti-Müllerian hormone(AMH)were strongly associated with increased PCOS risk induced by high copper exposure.The mediation analysis indicated a mediating effect of AMH in the association between copper exposure and PCOS risk. Conclusion Copper may affect PCOS risk through the hypothalamic-pituitary-ovarian axis,mediated by AMH.Copper exposure and internal AMH levels are important indicators for early warning of PCOS development.