Diminished ovarian reserve(DOR)is associated with a reduced quantity and/or quality of retrieved oocytes,usually leading to low numbers of retrieved oocytes and poor reproductive outcomes.DOR may potentially progress to premature ovarian insufficiency and premature ovarian failure,which have adverse impacts on women's health.There is currently no effective clinical treatment to rescue ovarian function.The limited availability of human ovarian tissues and medical ethics issues mean that animal models are crucial for improving our understanding of the molecular pathogenesis of DOR and identifying preventive and therapeutic targets.This review thus aims to summarize the techniques and strategies used to establish rodent models of DOR,to provide a reference for future studies.

Objective A comparison of two method of establishing pressure ulcer rat models to determine which is the most suitable for experimental use.Methods 18 male SD rats were randomly divided into control(n=6),model A(n=6)and model B(n=6)groups.In the control group,iodophor treatment was given after hair removal at the simulated modeling site.In model group A,longitudinal compression was performed by simple deep-tissue foreign body implantation.In model group B,transverse compression was performed via the magnet compression method.The times required to complete the process and for each stage of pressure ulcer model establishment in each group were recorded.The general condition of the rats was observed,and the modeling rate,mortality rate,and infection rate were compared.Results By naked eye,we observed that the model A and model B groups gradually developed redness and swelling,ulceration,bleeding,exudation,and necrosis.Comparison of the whole time to produce pressure uler between model A and model B groups:the difference between the two groups was statitically significant(P＜0.05).Comparison of the time to produce pressure injury between Model A and Model B:The difference between the two groups at stage Ⅰ was not statistically significant(P＞0.05);the difference between the two groups at stage Ⅱ was statistically significant(P＜0 05);the difference between the two groups at stage Ⅲ was statistically significant(P＜0 05);the difference between the two groups at stage Ⅳ was statistically significant(P＜0 05).The mental and sports scores of the rats in the control group were significantly different from those in the model A and model B groups(P＜0.05).The general state of rats in the model group A was significantly different from that in the model B group,and coat color was dimer and activity decreased in the model group A.The modelling rate of rats in both model A and model B groups was 100％.The mortality and infection rates of the model group A were higher than those of the model group B,which were 33.34％and 16.70％,respectively.Conclusions Successful preparation of a four-stage model of pressure ulers in both modalities.The two method have both commonalities and distinct characteristics.The magnet compression method required less time,the rats were generally in good condition,and the mortality and infection rates were low;thus it is suitable for short-term intervention research.The simple deep-tissue foreign body implantation method took longer,required rats to have a certain level of tolerance,had high infection and mortality rates,and is more suitable for use for long-term observations of pressure ulcers.

Objective:To gain a deeper understanding of the comorbidity status of elderly patients with coronary heart disease and the effect of comorbidity on their hospitalization costs.Methods:Using the convenient sampling method, a total of 8 334 elderly hospitalized patients diagnosed with coronary heart disease in Beijing Hospital from January 2018 to December 2021 were selected as the research objects. General Inforamtion Questionnaire and Charson comorbidity index (CCI) were used to investigate the comorbidity of patients.Results:Among the 8 334 elderly patients with coronary heart disease included, 88.18% (7 349/8 334) had comorbidity, and there was a statistically significant difference in hospital costs among patients with different CCI scores ( P<0.01). Elderly patients with coronary heart disease with comorbidity had higher hospital costs. The results of the binomial logistic regression analysis showed that comorbidities increased the hospitalization costs of elderly coronary heart disease patients in both the unadjusted model and the gradually adjusted model for age, gender, occupation, education level, admission department, admission status, admission year, admission mode length of stay and disease classification ( P<0.05) . Conclusions:The comorbidity in elderly patients with coronary heart disease is serious, which is an important factor affecting hospitalization costs. In medical practice, it is necessary to strengthen the comprehensive management of elderly patients with coronary heart disease, pay attention to the influencing factors of hospitalization costs, optimize prevention and treatment strategies, control the occurrence and progression of comorbidities among patients, deepen the reform of medical insurance payment methods such as grouping payments based on disease diagnosis, so as to accurately reduce hospitalization costs and promote the sustainable and healthy development of the medical and health system.

Objective To evaluate the feasibility of emergency percutaneous coronary intervention(PCI)with extracorporeal membrane oxygenation(ECMO)support in critically ill patients with acute myocardial infarction(AMI)and cardiogenic shock(CS).Methods Retrospective analysis of clinical data of AMI combined with CS patients admitted to the department of emergency of the Second Hospital of Hebei Medical University from December 2018 to December 2021,including gender,age,body mass index(BMI),past history(smoking,coronary heart disease,arrhythmia,diabetes,hypertension,hyperlipidemia,cerebrovascular disease);acute physiology and chronic health evaluation Ⅱ(APACHEⅡ)score,highest vasoactive-inotropic score(VIS)within 24 hours of admission,the worst auxiliary examination values within 24 hours after admission:blood lactic acid(Lac),arterial partial pressure of oxygen(PaO2),cardiac troponin I(cTnI),alanine aminotransferase(ALT),total bilirubin(TBil),creatinine(Cr),serum potassium,left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF)],presence of malignant arrhythmia or cardiac arrest during emergency PCI,completion of PCI,and the 30-day prognosis,etc.Patients were divided into an ECMO group and a non-ECMO group based on whether ECMO was applied,to analyze differences in the above indicators between the two groups.Results There were no statistically significant differences between the ECMO group and the non-ECMO group in terms of gender,age,BMI,past history,APACHEⅡ,VIS and the worst auxiliary examination value within 24 hours after admission.The incidence of malignant arrhythmia or cardiac arrest events and 30-day mortality rate during emergency PCI in the ECMO group were significantly lower than those in the non-ECMO group[the incidence of malignant arrhythmia or cardiac arrest during emergency PCI was 17.9％(7/39)vs.45.0％(9/20),and the 30-day mortality was 46.2％(18/39)vs.75.0％(15/20),both P<0.05].The completion rate of PCI in the ECMO group was significantly higher than that in the non-ECMO group[100.0％(39/39)vs.80.0％(16/20),P<0.05].Conclusions For critically ill patients with AMI combined with CS,ECMO support can reduce the risk of malignant arrhythmia or cardiac arrest during emergency PCI,increase the completion rate of PCI,and reduce the 30-day mortality.With the support of the ECMO team,ECMO support emergency PCI is feasible.

Objective:To explore the clinical characteristics of pregnancy complicated by primary Sj?gren's syndrome (pSS) and the related factors of adverse outcomes in pregnant women with pSS.Methods:A retrospective analysis was conducted on the clinical data of 32 pregnancies complicated by pSS treated in the Department of Obstetrics at the Third Affiliated Hospital of Guangzhou Medical University from February 2017 to August 2022. The patients were divided into two groups according to whether they had perinatal adverse outcomes: an adverse outcome group ( n=20) and a favorable outcome group ( n=12). The clinical characteristics of the two groups were compared with two independant sample t-test, Mann-Whitney U test, and Fisher's exact test, and multivariate logistic regression analysis was used to analyze the related factors of adverse outcomes in pregnant women with pSS. Results:(1) The average maternal age of the 32 pSS pregnancies was (32.9±4.6) years, the pre-pregnancy body mass index was (21.1±3.8) kg/m 2, and the median gestational age at delivery was 37.8 (35.4-38.5) weeks. There were 18 women (56.3%, 18/32) were diagnosed before pregnancy and 14 women (43.7%, 14/32) during pregnancy. Out of the 32 pregnancies, 25 (79.1%, 25/32) received therapy with glucocorticoids and/or hydroxychloroquine during pregnancy, whereas seven (21.9%, 7/32) had no medication during pregnancy. (2) The main adverse maternal outcomes included oligohydramnios (25%, 8/32), hypertensive disorder of pregnancy (18.8%, 6/32), preterm birth (18.8%, 6/32), fetal growth restriction (15.6%, 5/32), miscarriage (12.5%, 4/32), gestational diabetes mellitus (9.4%, 3/32), and postpartum hemorrhage (3.1%, 1/32). (3) Adverse neonatal outcomes included low birth weight infants in seven cases (25.0%, 7/28), neonatal asphyxia in seven cases (25.0%, 7/28), and two cases of congenital heart block (7.1%, 2/28). (4) The rate of diagnosis before pregnancy in the favorable outcome group was higher than the adverse outcome group [10/12 vs. 40.0%(8/20), Fisher's exact test, P=0.028]. There were no significant differences between the two groups concerning maternal age, pre-pregnancy BMI, weight gain during pregnancy, parity, rates of positivity for autoantibodies (antinuclear antibody, Sj?gren-specific antibody A, Sj?gren-specific antibody B, anti-Ro-52), and proportion of drug treatment (glucocorticoids, hydroxychloroquine) (all P>0.05). (5) Multivariate logistic regression analysis showed that diagnosis before pregnancy ( OR=0.02, 95% CI: 0.00-0.62, P=0.024) and positive Sj?gren-specific antibody B ( OR=0.01,95% CI: 0.00-0.75, P=0.038) were the protective factors. Conclusions:The clinical manifestations of pSS among pregnant women are varied and atypical,often with insidious onset. For pregnant women with pSS, being diagnosed before pregnancy, positive Sj?gren-specific antibody B may reduce adverse outcomes. It is important to address pre-pregnancy examination, early diagnosis and timely intervention to reduce the occurrence of adverse outcomes in pregnant women with pSS.

Dysregulation of histone deacetylases (HDACs) is closely related to tumor development and progression. As promising anticancer targets, HDACs have gained a great deal of research interests and two decades of effort has led to the approval of five HDAC inhibitors (HDACis). However, currently traditional HDACis, although effective in approved indications, exhibit severe off-target toxicities and low sensitivities against solid tumors, which have urged the development of next-generation of HDACi. This review investigates the biological functions of HDACs, the roles of HDACs in oncogenesis, the structural features of different HDAC isoforms, isoform-selective inhibitors, combination therapies, multitarget agents and HDAC PROTACs. We hope these data could inspire readers with new ideas to develop novel HDACi with good isoform selectivity, efficient anticancer effect, attenuated adverse effect and reduced drug resistance.

Objective To analyze the prognosis and influencing factors of patients with acute myocardial infarction(AMI)complicated with cardiogenic shock(CS)under extracorporeal membrane oxygenation(ECMO)support.Methods Retrospective analysis of the clinical data of ECMO supported coronary angiography and percutaneous coronary intervention(PCI)treatment for AMI complicated with CS patients who visited the department of emergency medicine of the Second Hospital of Hebei Medical University from December 2018 to December 2021,including gender,age,body mass index(BMI),past history(smoking history,coronary heart disease,diabetes,hypertension,hyperlipidemia,cerebrovascular disease),acute physiological and chronic health evaluationⅡ(APACHEⅡ),vasoactive-inotropic score(VIS),the worst auxiliary examination indicators within 24 hours before ECMO[arterial lactate acid,white blood cell count(WBC),cardiac troponin I(cTnI),alanine transferase(ALT),total bilirubin(TBil),creatinine(Cr),serum potassium(K+),left ventricular ejection fraction(LVEF)],time from onset to PCI,coronary angiography results(involved anterior descending branch,circumflex branch,right coronary artery,three-vessel lesions,left main artery lesions),whether to use intra aortic-balloon counterpulsation(IABP)and continuous renal replacement therapy(CRRT).Patients were divided into survival and death groups based on the prognosis after 30 days of onset.Univariate analysis was used to compare the differences in the above indicators between the two groups with different prognoses,Logistic regression analysis was used to analyze the independent risk factors affecting the prognosis of AMI patients with CS under ECMO support coronary angiography and PCI treatment,and the receiver operator characteristic curve(ROC curve)was drawn to evaluate the predictive value of risk factors on patient prognosis.Results Out of 39 patients,21 cases(53.8%)survived and 18 cases(46.2%)died.Compared with the survival group,the VIS score,lactate acid,time from onset to PCI,involvement of the circumflex artery,three-vessel disease,and left main artery lesions significantly increased in the death group(all P＜0.05).Logistic regression analysis showed that lactate acid and three-vessel lesions were independent risk factors affecting the 30-day prognosis of AMI patients with CS[odds ratio(OR)and 95%confidence interval(95%CI)were 1.845(1.018-3.342)and 107.171(1.307-8 785.901),all P＜0.05].ROC curve analysis showed that lactate acid and three-vessel lesions has predictive value for the prognosis of AMI combined with CS patients undergoing ECMO supported coronary angiography and PCI treatment,the area under the ROC curve(AUC)were 0.756 and 0.752,95%CI were 0.601-0.911 and 0.588-0.916,P value were 0.007 and 0.008.When the cut-off value of lactic acid was 5 mmol/L,the sensitivity and specificity of predicting the prognosis of AMI combined with CS patients undergoing coronary angiography and PCI treatment were 94.1%and 57.1%,respectively.Conclusions The indications for using ECMO in critically ill patients with AMI combined with CS need to be further refined.VIS score,lactate acid,time from onset to PCI,three-vessel lesions,and left main artery lesions are risk factors for patient death.When using ECMO support for high lactate,high VIS score,and three-vessel lesions,caution should be exercised.Early ECMO support can improve the prognosis of appropriate patients by reducing lactate,reducing the use of vasoactive drugs,and shortening the time from onset to PCI.

Objective To study the effect of Longxuejie capsule combined with Jiuhua ointment treatment on wound after ring-like mixed hemorrhoid surgery.Methods A total of 107 patients with ring-like mixed hemorrhoid (RMH) were randomly divided into the control group and the treatment group.All the patients were treated with the surgery,and then the control group were treated with Mayinglong ointment,while the treatment group were treated with Longxuejie capsule combined with Jiuhua ointment.The two groups were treated for 10 days.The clinical efficacy of the two groups after treatment were compared.The VAS score,edema degree score,wound drainage score,wound area score and wound granulation tissue score of the two groups were compared before and after treatment.The serum VEGF,PDGF and bFGF of the two groups were compared before and after treatment.The adverse reactions rates of the two groups during the treatment were compared.Results The total efficacy rate of the treatment group was 92.59％ (50/54),which was significantly higher than 77.4％ (41/53) of the control group (x2=4.881,P=0.027).After treatment,the VAS (0.8 ± 0.2 vs.1.6 ± 0.3,t=13.915),edema degree score(0.3 ± 0.2 vs.0.8 ± 0.2,t=12.690),wound drainage (0.2 ± 0.2 vs.0.7 ± 0.2,t=l 3.054),area (0.4 ± 0.2 vs.0.9 ± 0.3,t=10.044) and wound granulation tissue (0.4 ± 0.2 vs.0.7 ± 0.2,t=7.427) of the treatment group were significantly lower than the control group (P＜0.01).After treatment,the serum VEGF (126.43 ± 14.68 ng/L vs.107.78 ± 12.26 ng/L,t=7.126),PDGF (59.42 ± 9.73 ng/L vs.48.27 ± 7.08 ng/L,t=6.767) and bFGF (99.86 ± 12.61 ng/L vs.83.67 ± 11.15 ng/L,t=7.031) of the treatment group were significantly higher than the control group (P＜0.01).Conclusions Longxuejie capsule combined with Jiuhua ointment can promote the recovery of wound of the patients after ring-like mixed hemorrhoid surgery.Its mechanism may be correlated with regulation of the expressions of VEGF,PDGF and bFGF,and promotion of formation of granulation tissue growth and repair.

Objective To evaluate the value of stroke prognostication using age and National Institute of Health Stroke Scale index (SPAN) for outcome after early endovascular treatment for anterior circulation large vessel occlusion.Methods The patients who underwent early endovascular treatment were prospectively,sequentially collected in Yijishan Hospital of Wannan Medical College from December 2014 to September 2017 and Jinling Hospital from March 2014 to March 2017.Individuals whose age in years plus NIHSS score was greater than or equal to 100 were designated as SPAN-100-positive patients,while those with a score less than 100 were designated as SPAN-100-negative patients.We compared the baseline data and perioperative data between the two groups.The 90 days modified Rankin Scale score≤2 was regarded as favorable outcome.Single factor and multivariable Logistic regression analyses were used to determine the association between SPAN-100 and outcomes.Results One hundred and ninety patients were enrolled,20 (10.5％) of which were SPAN-100 positive,and 170(89.5％) were SPAN-100 negative.There were no significant differences between the two groups on postoperative intracerebral hemorrhage and 90 days mortality.Ninety days independence rates were higher in SPAN-100-negative patients (77/170,45.3％) than in SPAN-100 positive patients (4/20,20.0％;x2 =4.681,P =0.030).Multi-factor Logistic regression analysis showed that the higher preoperation systolic pressure (OR =1.030,95％ CI 1.008-1.052,P =0.007),the lower Alberta Stroke Program Early CT Score (OR =1.609,95％ CI 1.056-2.453,P =0.027) and poor collateral circulation(OR =5.714,95％ CI 1.668-19.570,P =0.006) were the independent risk factors of outcomes.Conclusion SPAN-100 is not an independent predictor of favorable outcome after adjusting for factors of outcomes in patients with anterior circulation large vessel occlusion.

Objective: To investigate the heart rate control situation of chronic heart failure (CHF) patients who received cardiovascular implantable electronic device (CIED) therapy, and to assess the heart rate control efficacy by optimized medication adjustment. Methods: We performed a perspective study in heart failure with reduced left ventricular ejection fraction (HFrEF) patients who received CIED according to guideline recommendations, patients were enrolled from January 2012 to January 2017. Resting heart rate (RHR) recorded by electrocardiogram after 10 minutes' rest and medication usage within 1 month were recorded at baseline. RHR less than 70 beats per minute (bpm) was regarded as well controlled. β-receptor blockers and (or) ivabradine would be added in patients whose RHR were over 70 bpm. RHR after optimized medication adjustment was recorded during follow-up period. Results: One hundred and fifty patients were included in this study with average RHR (80.6±11.9) bpm. RHR was<70 bpm in 27.3% (41/150) patients at baseline and β-receptor blockers was underused in 80.7% patients (88/109) whose RHR was>70 bpm. The overall RHR decreased to (73.1±10.4) bpm and percent of patients with RHR<70 bpm increased to 70.0% (105/150) after up-titration of β-receptor blockers compared to baseline (χ²=52.958, P<0.001). Ivabradine was added in the rest 45 patients and RHR was<70 bpm in 43 out of 45 patients after ivabradine use. The overall RHR decreased to (67.1±2.7) bpm and percent of RHR<70 bpm significantly increased to 98.7% (148/150) (χ²=44.504, P<0.001 vs. up-titration of β-receptor blockers only). Conclusion RHR in CHF patients who received CIED therapy is not ideally controlled in this patient cohort, individual up-titration ofβ-receptor blockers and ivabradine use may help to optimize RHR in these patients.