OBJECTIVES: To assess the efficacy and safety of Tiaozhou Ziyin (TZZY) recipe for treatment of premature ovarian insufficiency (POI) and explore the possible mechanisms. METHODS: We used bioinformatics analyses and network pharmacology to identify the main active ingredients in TZZY recipe and their core targets, which were verified by Western blotting. We tested the efficacy and safety of the recipe in 60 POI patients, who were randomized into control group (n=30) with Femoston treatment and TZZY group (n=30) with additional TZZY recipe treatment for 3 menstrual cycles. RESULTS: The core active ingredients of TZZY recipe included kaempferol, β-sitosterol, luteolin, and quercetin. The core targets included SRC, TP53, STAT3, PIK3CA, and MAPK3, which were involved in positive regulation of cell movement and protein phosphorylation, the cancer pathways and the PI3K-Akt signaling pathway. Molecular docking showed that the core active ingredients had good binding ability with the core targets. In female rat models of POI, TZZY recipe treatment significantly up-regulated ovarian expressions of p-PI3K and p-Akt proteins. In the clinical trial, treatment with Femoston and Femoston plus TZZY recipe both significantly increased E₂ levels and reduced FSH and LH levels and Kupperman scores of the patients, and the combined treatment produced significantly stronger effects. Both treatments increased the number of antral follicles of the patients, but the combined treatment also significantly increased the levels of AMH. CONCLUSIONS The therapeutic mechanism of TZZY recipe for POI involves multiple active ingredients, multiple therapeutic targets and multiple pathways, and activating the PI3K /Akt pathway is one of its main mechanisms of action, to improve ovarian reserve function, alleviate clinical symptoms, and enhance clinical efficacy in POI patients.
Female ; Primary Ovarian Insufficiency/drug therapy* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Rats ; Molecular Docking Simulation ; Signal Transduction ; Sitosterols/therapeutic use* ; Kaempferols/therapeutic use*

Objective:To explore the therapeutic effect of cognitive behavioral therapy (CBT) combined with family intervention on obsessive-compulsive disorder (OCD).Method:A total of 28 patients with OCD who visited the outpatient department of Xiamen Xianyue Hospital from June 2021 to June 2022 were randomly divided into intervention group( n=13)and control group( n=15).Patients in the intervention group and the control group were both received routine drug treatment. On this basis, the patients in intervention group received the treatment of CBT combined with family intervention, while the patients in control group only received CBT treatment.The participants were evaluated at baseline, post-intervention, 1 month and 3 months after the intervention. The Yale-Brown obsessive compulsive scale (Y-BOCS) was used to evaluate the severity of symptoms, and the Sheehan disability scale (SDS) was used to assess their function impairment in patients.The family accommodation scale for OCD interviewer-rated (FAS-IR) was employed to assess family members' family accommodation behavior. Changes in scores on the Y-BOCS scale, SDS scale, and FAS-IR scale scores at each observation time point were used as outcome indicators. The t-test, χ2-test and repeated measure ANOVA were used for statistical analysis by SPSS 25.0 software. Results:(1)The interaction effect of Y-BOCS score between time and group before and after intervention was significant ( F=4.748, P<0.05). The results of the simple effects test showed that the Y-BOCS score of the intervention group at 1 month after the intervention(20.63±5.23)was lower than that of the baseline(27.23±5.12)and post-intervention(24.85±5.94)(both P<0.05). The Y-BOCS score of the intervention group at 3 months after the intervention (16.85±4.62)was lower than that of the baseline, post-intervention, and 1 month after the intervention (all P<0.05). The Y-BOCS score of the control group at 3 months after the intervention(20.93±7.51) was lower than that of the baseline(25.93±4.68)and post-intervention(25.53±6.57)(both P<0.05).(2)The interaction effect of SDS score between time and group before and after intervention was significant ( F=54.88, P<0.01). The results of the simple effects test showed that the SDS score of the intervention group at post-intervention was lower than that of the baseline( P<0.05).The SDS score at 1 month after the intervention was lower than that of the baseline and post-intervention (both P<0.05). The SDS score of the intervention group at 3 months after the intervention was lower than that of the baseline, post-intervention, and 1 month after the intervention (all P<0.05). At 3 months after the intervention, the SDS score of the intervention group was lower than that of the control group ( P<0.05).(3)The interaction effect of FAS-IR score between time and group before and after intervention was significant ( F=20.285, P<0.01). The results of the simple effects test showed that post-intervention, the FAS-IR score of the intervention group was lower than that of the baseline( P<0.05).The SDS score at 1 month after the intervention was lower than the baseline and post-intervention (both P<0.05). The FAS-IR score of the intervention group at 3 months after the intervention was lower than that of the baseline, post-intervention, and 1 month after the intervention (all P<0.05). At 3 months after the intervention, the FAS-IR score of the intervention group was lower than that of the control group ( P<0.05). Conclusion:The CBT combined with family intervention can improve the treatment outcome of OCD, patients' functional impairment, and reduce the occurrence of family accommodation behavior, which providing a basis for family intervention in OCD.

Atractylodis rhizoma is a perennial herb of the Asteraceae family,which mainly divided into A.chinensis(DC)Koidz and Atractyiodes lancea(Thunb)DC,with the effects of strengthening the spleen,drying dampness,brightening the eyes,etc.Atractylodis rhizoma is mainly used in the clinical treatment of spleen deficiency and dampness,night blindness,eye fatigue and other symptoms.According to the clinical effect,and modern pharmacological researches have confirmed,the Chinese herbal medicine Atractylodis rhizoma contains a variety of active ingredients,such as volatile oils,alkynes,glycosides,etc.In recent years,pharmacological studies on Atractylodis rhizoma have found that atractylodin in polyalkynes has good activity in anti-inflammation,treatment of bacterial resistance,and inhibition of cholangiocarcinoma cell migration,and its high biological activity may be related to the conjugated enyne structure.Therefore,this article summarizes the studies on chemical components and pharmacological effects of polyalkynes in Atractylodis rhizoma that have been published in recent years,and comprehensively expounds the research progress of polyalkynes in Atractylodis rhizoma,so as to provide reference for scientific researchers and promote the in-depth development and utilization of the medicinal value of Atractylodis rhizoma.

OBJECTIVE Na+/K+-ATPase(NKA)is a large membrane protein expressed universally in all cells.It is indispensable for the maintenance of ionic gradient.We previously reported that the dysfunction of this pump in neurons and astrocytes contributes to stroke and neurodegenerative diseases,respectively.However,its roles in the microglia and stress-related diseases are still unclear.METHODS Two classical models,chronic restraint stress(CRS)model and electronic foot shock(ES)model,were used to study the pathogenesis of anxi-ety in either NKAα1 global knockout(NKAα1 GKO)mice or NKA α1 conditional knockout(NKAα1 CKO)mice.Behavioral tests like open-field test,elevated plus maze,Morris water maze,novel object recognition test and gait imaging test were performed.A variety of molecular bio-logical methods were employed,including RNA sequenc-ing(RNA-seq)analyses,immunofluorescence and elec-trophysiological recordings etc.RESULTS NKAα1 defi-ciency had a broad impact on physical stress-induced anxiety-like behavior,but failed to exacerbate CRS induced memory deficits.Electrophysiology experiment showed that NKAα1 GKO and NKAα1 CKO mice exhibit-ed neuronal hyperexcitability under chronic stress.The underlying mechanisms may involve neuroinflammation,as NKAα1 deficiency exacerbated stress-induced microg-lia activation in vivo.Similarly,inhibition or downregula-tion of NKA α 1 aggravated LPS + ATP-induced inflam-mation in vitro.DR5-12D,a monoclonal antibody against the DR-region of NKAa1,improved stress-induced anxiety-like behavior through amelioration of the neuronal hyper-excitability and neurogenesis deficit in the ventral hippo-campus of mice.CONCLUSION NKA is closely related to neuroinflammation in microglia and DR-region of NKA a1 subunit may serve as a novel target to treat stress-induced anxiety.

Pulmonary hypertension (PH) is an extremely malignant pulmonary vascular disease of unknown etiology. ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine, thereby affecting RNA expression. However, the role of ADAR1 in PH development remains unclear. In the present study, we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular remodeling. Overexpression of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells (PASMCs). Conversely, inhibition of ADAR1 produced opposite effects. High-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in PH. CircCDK17 level was significantly lowered in the serum of PH patients. The effects of ADAR1 on cell cycle progression and proliferation were mediated by circCDK17. ADAR1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from m1A modification. We demonstrate for the first time that ADAR1 contributes to the PH development, at least partially, through m1A modification of circCDK17 and the subsequent PASMCs proliferation. Our study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease.

Objective: To improve physical activity by assessing pedometer-based physical activity during specific intervals over a week, among junior high school students,and to provide a reference for improving the level of students’ physical activity. Methods: Students (n=675) of grades 6-8 from six public junior high schools in Shanghai were recruited and instructed to wear a pedometer for a week, step counts and contents were recorded over a specific period. This period mainly included steps taken on the way to and from school, at school, at home in the evening on weekdays, and in the morning, afternoon, and evening on weekends. Results: The daily step counts recorded were 8 332 steps, with those on weekdays showing significantly higher values than step counts on weekends (9 065 steps vs. 6 392 steps)(t=22.9, P<0.01). Proportionately, the physical activity level at school contributed more to daily step counts (61.3%), followed by those on the commute to and from school(25.5%). Boys were more active than girls. For all intervals on weekdays, the step counts of students in rural districts, with overweight or obese, in grades 6 and 7, were higher than those in urban districts, with normal status, in grade 8 respectively (P<0.05). Low-activity students with physical education were more active than one without physical education(t boy=1.99,t girl=2.45,P<0.05). Conclusion These findings facilitate the implementation of effective, feasible interventions to enhance physical activity over a series of intervals during the day.

Objective To investigate the correlation of right ventricular (RV) to left ventricular (LV) volume ratio (RVv/LVv) measured by chest CT with pulmonary arterial pressure estimated by echocardiography before lung transplantation.Methods We reviewed 104 cases of lung transplant.According to the mean pulmonary arterial pressure (mPAP) exceeding 25 mmHg by right heart catheterization,hypertensive group (n =74) and normotensive group (n =30) were set up.Risk factors were assessed individually and adjusted for confounding by a multivariable logistic regression analysis.The area under the curve (AUC) for predicting pulmonary hypertension on chest CT and echocardiography was calculated.Results RVv/LVv and echocardiography-derived ptlmonary arterial systolic pressure (PASP) were significantly different between the two groups (P ＜ 0.05).In the hypertensive group,there was strong correlation between the RVv/LVv and PASP from catheterization (R =0.82,P＜0.001),also between the P ASP from echocardiography and catheterization (R =0.60,P＜ 0.001).The ROC curve displayed that with 0.85 as the cutoff for RVv/LVv,the sensmitivity,specificity and accuracy rate for predicting mPAP over 25 mmHg were 87.5％,91.8％ and 90.9％,respectively.The ROC curve also displayed that based upon an echocardiography-derived PASP of 35 mmHg as the cutoff point,the sensitivity,specificity and accuracy rate for predicting mPAP over 25 mmHg were 91.2％,90.8％ and 88.4％,respectively.Conclusion RV/LV volume ratios on chest CT and echocardiographic evaluation correlate well with PASP assessed by right heart catheterization and can be used to predict pulmonary hypertension with high sensitivity and specificity.

Objective To investigate the selection of recipients,operative technique,and perioperative management of lung transplantation for chronic thromboembolic pulmonary hypertension.Methods This article reviews the clinical data of 6 patients with chronic thromboembolic pulmonary hypertension receiving lung transplantation from January 2012 to June 2016.From January 2012 to June 2016,6 patients with chronic thromboembolic pulmonary hypertension underwent lung transplantation at Department of Thoracic Surgery,Affiliated Wuxi People's Hospital,Nanjing Medical University.There were 4 male and 2 female patients aged from 34 to 59 years.Chest enhancement of CT or CTPA in 6 patients prior to transplantation suggests a different degree of pulmonary embolism.The mean pulmonary artery pressure (mPAP) was＞30 mmHg,NYHA 11Ⅰ or Ⅳ.Four patients received bilateral sequence lung transplantation (BSLT) under extracorporeal membrane oxygenation (ECMO) support.Two patients received single lung transplantation (SLT).We analyzed the differences of oxygenation index,pulmonary systolic pressure,pulmonary artery diastolic pressure,mean pulmonary arterial pressure,and central venous pressure before and after treatment.Using paired t test to compare these indicators,P＜0.05 was considered statistically significant.Results The oxygenation index increased from (195 ± 85) to (440 ± 140) mmHg after treatment,the difference was statistically significant (P＜0.05).the The systolic pressure of pulmonary artery was decreased from (108 ± 28) mmHg to (56 ± 16) mmHg,and the difference was statistically significant (P＜0.05).the The diastolic pressure of pulmonary artery was decreased from (72 ± 18) mmHg to (25 ± 10) mmHg,and the difference was statistically significant (P＜0.05).the The mean pulmonary artery pressure was decreased from (84 ± 27) mmHg to (36 ± 10) mmHg,and the difference was statistically significant (P＜0.05).the The central venous pressure was decreased from (17.5 ± 4.5) mmHg to (8.5 ± 1.5) mmHg,and the difference was statistically significant (P＜0.05).Finally,5 patients were discharged from the hospital,and the pulmonary valve? functioned? well.1 patients died of shock and systemic failure 3 days after operation.Conclusion Lung transplantation is effective in the treatment of chronic thromboembolic pulmonary hypertension,and long-term survival requires further investigations.

AIM: To investigate the influence of Sini decoction (SND) on the proliferation and apoptosis of rabbit abdominal aorta smooth muscle cells after ballon injury and discuss the effect of vascular smooth muscle cell's (VSMCs) proliferation and apoptosis in post-percutaneous coronary intervention (PCI) restenosis (RS) and the feasibility of SND preventing post-PCI RS. METHODS: The animal model of rabbit abdominal aorta ballon injury was set up and the therapertic group was treated with SND. The shape of proliferative and apoptotic cell were investigated by electron microscope. Immunohistochemistry staining was performed using ?-actin,PCNA and Cyclin E monoclonal antibodies. In situ Cell Death Detection Kit was used to identify apoptotic cells. Abdomial aorta angiography was operated in the 84th day subgroup and the stenosis degree was evalued by quantitative angiographic analysis. RESULTS: As compared with the control group, the therapeutic group displayed a lower proliferative percentage and a higher apoptosic percentage (P