Objective:To explore the effects of Tongdu Tiaoshen acupuncture on vascular endothelial function and inflammatory factors in patients with mild cognitive impairment (MCI) after ischemic stroke (IS).Methods:A retrospective analysis was performed on the clinical data of 71 patients with MCI after IS in the hospital between January 2020 and September 2022. According to different treatment methods, they were divided into Tongdu Tiaoshen acupuncture group ( n=31, Tongdu Tiaoshen acupuncture + oral nimodipine tables) and routine body-acupuncture group ( n=40, routine body-acupuncture group + oral nimodipine tables). Both groups were treated for 2 courses (14 d/course). Before and after treatment, levels of serum NO and endothelin-1 (ET-1) were detected by radioimmunoassay, and levels of serum basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), plasma homocysteine (Hcy) and IL-6 were detected by ELISA. The cognitive function of patients was evaluated and intelligence level by Montreal Cognitive Assessment Scale (MoCA), Mini-Mental State Examination(MMSE) and the clinical curative effect was also evaluated. Results:The total response rates in Tongdu Tiaoshen acupuncture group and routine body-acupuncture group were 90.32% (28/31) and 70.00% (28/40), and the difference between the two groups was statistically significant ( χ2=4.33, P=0.037). After treatment, levels of plasma Hcy and IL-6 in Tongdu Tiaoshen acupuncture group were lower than those in the routine body-acupuncture group ( t=2.57, 9.36, P<0.05 or P<0.01). After treatment, levels of serum bFGF, VEGF and NO in Tongdu Tiaoshen acupuncture group were significantly higher than those in the routine body-acupuncture group ( t=10.03, 9.29, 8.17, P<0.01), while ET-1 level was significantly lower than that of the routine body-acupuncture group ( t=2.41, P=0.019). After treatment, MoCA score [(28.24±4.45) vs. (25.32±4.34), t=2.78], MMSE score [(28.73±1.44) vs. (28.02±1.22), t=2.25] in Tongdu Tiaoshen acupuncture group were higher than those in the routine body-acupuncture group ( P<0.01). Conclusion:Tongdu Tiaoshen acupuncture is beneficial to improve vascular endothelial function, reduce levels of inflammatory factors, promote the recovery of cognitive function and improve curative effect in patients with MCI after IS.

Objective To discover 5-HT2A receptor antagonist molecules with novel structures and explore their structure-activity relationship through structure-and mechanism-based drug design,synthesis and activity evaluation.Methods The way in which pimovanserin interacted with 5-HT2A receptor was analyzed via molecular docking,molecular dynamics simulation and binding free energy calculations.Based on the results of this study,the 5-HT2A receptor antagonist target compounds with novel structures were designed using pimovanserin as the lead molecule.According to the structures of target compounds,corresponding synthetic routes were designed.The heterocyclic methylamine intermediates were obtained by reductive amination or reduction reaction from heterocyclic formaldehyde or heterocyclic methanonitrile before being reacted with 4-(4-fluorobenzylamino)-1-methylpiperidine to obtain the target compounds using CDI urea synthesis method.The inhibitory activity of the target compounds against 5-HT2A receptor was tested at the cellular level,and the anti-hallucinogenic effects of the target compounds were tested in the mouse head twitch response model.Results Twelvenovel compounds were synthesized and their structures were confirmed by HR-MS,1H-NMR and 13C-NMR.The results of the activity assay showed that compounds 6a,6c and 6d exhibited better 5-HT2Areceptor inhibitoryactivity with IC50 values of 120,152 and 285 nmol/L,respectively while compounds 6c and 6d exhibited better anti-hallucinogenic activity in mice with inhibition rates of 97.0％and 82.9％(10 mg/kg),respectively.Conclusion The novel compound 6c and 6d have shown strong 5-HT2A receptor inhibitoryactivity and anti-hallucinogenic activity and deserve more research.Structure-activity relationship analyses of target compounds indicate that the repulsion of the heterocyclic ring with basic N atoms and the accommodation of the heterocyclic ring without basic N atoms by the side extended pocket of the 5-HT2A receptor could significantly affect the ex vivo and in vivo effects of antagonists.

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC₅₀ values and achieved picomolar DC₅₀ values and >99% of maximum degradation (D_max) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-MET^Y1230H and c-MET^D1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.

Gonorrhea, caused by Neisseria gonorrhoeae, is one of the most frequently reported infectious diseases. With the increasing antibiotic resistance in Neisseria gonorrhoeae, gonorrhea has become a major public health problem worldwide, making it imperative to develop a safe and effective vaccine. Lipooligosaccharides (LOS), which exist on the outer surface of gram-negative bacteria, contain many important antigenic determinants. In recent years, a large number of studies have shown that LOS may become the most potential target of Neisseria gonorrhoeae vaccine and immunotherapy. This article reviewed the structure of LOS, its role in Neisseria gonorrhoeae infection, research progress in LOS vaccine and the challenges faced in vaccine development, aiming to provide reference for further study.

Objective To determine the management of family planning technology services in Changning District of Shanghai over the past decade， and to explore the key populations and service patterns along with changing family planning policy， so as to provide evidence for further family planning services and management. Methods Based on the routine statistics， family planning surgery， management of key populations， management of surgery quality， and contraceptive counseling from 2011 through 2020 in Changning District were retrospectively reviewed. Results The number of family planning surgery， induced abortion， midtrimester induced abortion， live births， and birth to induced abortion ratio has decreased. Majority of those who received induced abortion were non-local married women， whereas those under 19 years were principally non-local unmarried ones. In total， contraceptive counseling decreased among newly married couples and in the community. Postpartum contraceptive counseling guidance remained at a low level. Furthermore， the number of IUD placements and subcutaneous implants has reduced， suggesting the acceptance of highly effective methods of contraception needs to be improved. The percentage of immediate IUD placement following induced abortion gradually increased. In addition， the percentage of high-risk family planning surgery showed a decreasing trend， however， serious surgical complications remained. Conclusion With the “universal two-child” policy， the number of family planning surgery， especially induced abortions， has decreased significantly. It warrants a demand-driven family planning services， including strengthening the multiple health education and promoting to having a second child for key populations. Moreover， we should optimize the service process， strengthen the professional training for relevant clinicians and staff， and improve the quality of services for ensuring the mother and child health.

Thoracic aortic dissection (TAD) without familial clustering or syndromic features is known as sporadic TAD (STAD). So far, the genetic basis of STAD remains unknown. Whole exome sequencing was performed in 223 STAD patients and 414 healthy controls from the Chinese Han population (N = 637). After population structure and genetic relationship and ancestry analyses, we used the optimal sequence kernel association test to identify the candidate genes or variants of STAD. We found that COL3A1 was significantly relevant to STAD (P = 7.35 × 10
Aneurysm, Dissecting/genetics* ; Case-Control Studies ; Cluster Analysis ; Cohort Studies ; Collagen Type III/genetics* ; Computational Biology ; Genetic Predisposition to Disease ; Humans

BACKGROUND: As one of the most common endocrinal disorders for women at childbearing age, the diagnostic criteria of polycystic ovary syndrome (PCOS) have been defined differently among different international health organizations. Phenotypic heterogeneity of PCOS also brings about difficulties for its diagnosis and management assessment. Therefore, more efficient biomarkers representing the progression of PCOS are expected to be integrated into the monitoring of management process using metabolomic approaches. METHODS: In this prospective randomized controlled trial, 117 PCOS patients were enrolled from December 2016 to September 2017. Classical diagnostic parameters, blood glucose, and metabolome were measured in these patients before and at 2 months and 3 months of different medical interventions. The receiver operating characteristic (ROC) curves were built based on multivariate statistical analysis using data at baseline and 3 months' management, and combinational biomarkers with appreciable sensitivity and specificity were selected, which then validated with data collected at 2 months. RESULTS: A set of metabolites including glutamic acid, aspartic acid, 1-methylnicotinamide, acetylcarnitine, glycerophosphocholine, and oleamide were filtered out with high performance in representing the improvement through 3-month management of PCOS with high sensitivity and specificity in ROC analysis and validation with other two groups showed an appreciable area under the curve over 0.96. CONCLUSIONS: The six metabolites were representative of the remission of PCOS through medical intervention, making them a set of potential biomarkers for assessing the outcome of PCOS management. TRIAL REGISTRATION ClinicalTrials.gov, NCT03264638.
Biomarkers ; Female ; Humans ; Metabolomics ; Polycystic Ovary Syndrome/diagnosis* ; Prospective Studies ; ROC Curve

The elbow is more susceptible to motion loss than other joints after trauma,and elbow stiffness leads to functional impairment in the upper limb and interferes with daily activities.Open arthrolysis is the most common and classical treatment for post-traumatic elbow stiffness.In this paper,we review the treatment protocols like preoperative clinical evaluation,arthrolysis strategies and postoperative rehabilitation program for post-traumatic elbow stiffness,discuss relevant issues and assess their prospects.

Objective: To carry out the 4^th round of third-party evaluation on the implementation and effect of the 1^st year of the 2^nd Phase National Healthcare Improvement Initiative(abbreviated as Initiative)since 2015. Methods: The 4^th round of the evaluation survey adopted the same methods, organization and execution, and technical roadmap as the former three rounds of evaluations. Results: The 4^th round of evaluation was carried out from 18 March to 9 April, 2019 at 185 public hospitals in 31 provinces(autonomous regions, municipalities directly under the Central Government)and Xinjiang Production and Construction Corps.Facility survey, health professional survey and patient survey were conducted at each of the sample health facilities. A total of 120 782 valid questionnaires were collected from 144 non-psychiatric health facilities, 16 246 valid questionnaires were obtained from 41 psychiatric health facilities, and 252 cases of outstanding departments/hospitals in healthcare improvement were also collected. The average overall scoring of the 12 dimensions to assess Initiative implementation at 144 non-psychiatric health facilities was 84.4%. The overall outpatient satisfaction scoring was 91.1%, 96.7%for the inpatients. The overall inpatient satisfaction(family members inclusive) at 41 psychiatric health facilities was 93%. Areas remaining to be improved include day-surgery, telemedicine and medical social work. Compared with technical services, non-technical care should be further strengthened. The compensation, workload and work environment of the healthcare providers are still to be improved. Conclusions The implementation of the Initiative by health facilities has been greatly improved. The percentage of health facilities and patients who had positive perceptions of improved doctor-patient relationship has been increasing. Patient care experiences at public hospitals have been generally improved, and the implementation of promoting traditional Chinese Medicine practices also made progress. However, work satisfaction of healthcare providers was found to be rather low, compared to the high level of patient satisfaction.

Objective To explore the effect of low-dose or standard-dose conjugated equine estrogen (CEE)combined with natural progesterone or dydrogesterone on bone density in menopause syndrome women.Methods Totally 123 patients with menopause syndrome were recruited and randomly assigned to 3 treatment groups: group A(low-dose CEE+progesterone), group B(standard-dose CEE+progesterone), group C(standard-dose CEE+dydrogesterone). Using continuous sequential regimen, the duration of intervention was 12 cycles.The bone mineral density of lumbar 2-4 and neck of femur,the bone metabolic markers, the level of FSH and estradiol were examined just before the drug administration and 12 months after the beginning of experiment. Results There were 107 cases completed the one year trial.(1)Bone density:after 12 cycles of treatment,there was no significant change in bone density in group A(P>0.05);lumbar vertebrae of group B and C increased significantly,at 3.0% and 2.1%respectively(all P<0.05).The bone density of left femoral neck of group C significantly increased by 2.9%(P=0.029). There was no significant difference among the treatment groups at the beginning of experiment(P>0.05).(2)Bone metabolic markers: after 12 cycles of treatment, the levels of calcium, phosphorus, alkaline phosphatase, Ca/Cr decreased significantly,the difference were statistically significant(all P<0.05).There was no significant difference among the treatment groups at the beginning of experiment(P>0.05).(3)Levels of FSH and estradiol:after 12 cycles of treatment,the levels of FSH in three groups were decreased significantly(all P<0.01). The levels of estradiol in three groups were increased significantly(all P<0.01). There was no significant difference among the treatment groups at the beginning of experiment(P>0.05). Conclusions Both low-dose and standard-dose menopause hormone therapy(MHT)could elevate the level of estradiol, reduce bone turnover, prevent bone loss of postmenopausal women effectively. The standard dose of MHT could also increase the density of vertebrae and femoral neck,and generate more clinical benefits.