In this study, we explored the pharmacological effects of Siwu Decoction in treating premature ovarian insufficiency(POI) and its molecular mechanism based on the mitophagy pathway modulated and mediated by estrogen receptor(ER) subtypes. Female Balb/c mice were divided into a control group, model group, as well as high-dose and low-dose groups of Siwu Decoction. The POI mice model was constructed by intraperitoneal injection of cisplatin. The high-dose and low-dose groups of Siwu Decoction were administered intragastrically with Siwu Decoction each day for 14 days. During this period, we monitored the estrous cycle and body weight of the mice and calculated the ovarian index. The morphology of the ovaries was detected by hematoxylin-eosin(HE) staining, and the number of primordial follicles was counted. The apoptosis of the ovarian tissue was detected by TUNEL staining. The expression levels of anti-Müllerian hormone(AMH), apoptosis-associated and mitophagy-associated proteins, ER subtypes, and the expression levels of key proteins of its mediated molecular pathways were detected by Western blot and immunohistochemistry. KGN cells were divided into a control group, model group, Siwu Decoction group, and gene silencing group. The apoptosis model was induced by H_2O_2, and PTEN-induced putative kinase 1(PINK1) gene silencing was induced by siRNA transfection. The Siwu Decoction group and gene silencing group were added to the medium containing Siwu Decoction. Cell viability was detected by CCK-8 assay. Cell senescence was detected by senescence-associated-β-galactosidase. The expression levels of apoptosis-associated and mitophagy-associated proteins were detected by Western blot. The results of in vivo experiments showed that compared with the model group, the mice in the high-dose and low-dose groups of Siwu Decoction significantly recovered the rhythm of the estrous cycle, and the levels of ovarian index, number of primordial follicles, and expression of AMH, representative indexes of ovarian function, were significantly higher, suggesting that the level of ovarian function was significantly improved. The expression levels of the apoptosis-related proteins, cytochrome C(Cyt C), cysteinyl aspartate specific proteinase 3(caspase 3), B-cell lymphoma-2(Bcl-2)-associated X(Bax), and mitophagy-associated indicator(Beclin 1) were significantly decreased, and the expression levels of Bcl-2 was significantly elevated. The positive area of TUNEL was significantly reduced, suggesting that the apoptosis level of the ovaries was significantly reduced. The expression levels of PINK1, Parkin, and sequestosome 1(p62) were significantly reduced, suggesting that the level of ovarian mitophagy was significantly down-regulated. The expression levels of ERα and ERβ were significantly elevated, and the ratio of ERα/ERβ was significantly reduced. The expression levels of key proteins in the pathway, phosphoinositide 3-kinase(PI3K) and protein kinase B(Akt), were significantly reduced, suggesting that the regulation of ER subtypes and the mediation of PI3K/Akt pathway were the key mechanisms. In vitro experiments showed that compared with the model group, the proportion of senescent cells in the Siwu Decoction group was significantly reduced. Cyt C, caspase 3, Beclin 1, Parkin, and p62 were significantly reduced, which was in line with in vivo experimental results. The proportion of senescent cells and the expression level of the above proteins were further significantly reduced after PINK1 silencing. It can be seen that Siwu Decoction can regulate the expression level and proportion of ER subtypes in KGN cells, then mediate the PI3K/Akt pathway to inhibit excessive mitophagy and apoptosis, and exert therapeutic effects of POI.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Mitophagy/drug effects* ; Primary Ovarian Insufficiency/physiopathology* ; Mice ; Mice, Inbred BALB C ; Humans ; Receptors, Estrogen/genetics* ; Apoptosis/drug effects* ; Ovary/metabolism* ; Signal Transduction/drug effects* ; Anti-Mullerian Hormone/genetics*

OBJECTIVE: To distinguish the ambiguous genotyping results of human leukocyte antigen (HLA), identify a novel HLA-B allele and analyze the nucleotide sequence. METHODS: A total of 2 076 umbilical core blood samples from the Zhejiang Cord Blood Bank in 2022 were detected using the next generation sequencing technology (NGS) based on the Ion Torrent S5 platform. Among these a rare HLA-B allele with ambiguous combination result containing a base mutation was identified, and was further confimed by the third-generation sequencing (TGS) based on the nanopore technology. RESULTS: The NGS typing result of HLA-B locus showed HLA-B* 46:18, 54:06 or HLA-B*46:01, 54:XX (including a base mutation), and nanopore sequencing confirmed the typing as HLA-B*46:01, 54:XX (including a base mutation). Compared with HLA-B*54:01:01:01, the HLA-B*54:XX allele showed one single nucleotide substitution at position 1014 T>C in exon 6, with no amino acid change. The nucleotide sequence of the novel HLA-B*54:XX has been submitted to the GenBank nucleotide sequence database and the accession number OP853532 was assigned. CONCLUSION A ambiguous genotyping of the HLA-B Locus detected by NGS was distinguished by nanopore sequencing and a new HLA-B allele was successfully identified, which was officially named as HLA-B*54:01:11 by the World Health Organization Nomenclature Committee for Factors of the HLA System.
Humans ; High-Throughput Nucleotide Sequencing ; Alleles ; HLA-B Antigens/genetics* ; Genotype ; Mutation ; Sequence Analysis, DNA ; Base Sequence

Objective:To explore the understanding on health-related quality of life(HRQoL)among the Chinese populations and to develop a HRQoL conceptual framework that can be used to guide the development of Chinese HRQoL instruments.Methods:Respondents of Chinese general population and patients populations were recruited from 31 provinces in China.One-to-one semi-structured qualitative interviews were conducted to collect the views and perceptions on HRQoL.Based on the grounded theory,multi-level coding of qualitative interviews was carried out,and the framework method was used to sort out and summarize the coding to develop the HRQoL conceptual framework in China.Results:A total of 68 respondents were included in the study.The study extracted 1 558 open coding from the qualitative interview,which were analyzed and sorted into 180 axial coding and 31 selective coding(dimensions).The HRQoL conceptual framework for the Chinese population with 6 themes was finally summarized.Conclusions:The HRQoL conceptual framework based on the health concepts and preferences of the Chinese population contains 6 themes,refers to symptoms,physical function,emotion,cognition,activities and social function.In particular,the items of appetite,sleep and fatigue identifies may reflect Chinese cultural specific perceptions on important aspects of HRQoL.

OBJECTIVE: To analyze characteristics and related factors of the plantar pressure during the level walking and single leg standing in the chronic ankle instability (CAI) individuals. METHODS: From April 2019, 75 CAI individuals and 40 healthy individuals were enrolled in this study. Both of the static and dynamic plantar pressure were measured during six times level walking and three times single leg standing testing. The data including peak force, time to peak force in various foot contact areas and the time to boundary (TTB) and velocity of center of pressure (COP) were measured and compared between the affected side and the unaffected side and between the CAI cases and the healthy individuals. The correlations between the plantar pressure and the gender, Beighton score, affected side and body mass index (BMI) were analyzed. RESULTS: The characteristics of plantar pressure distribution in the CAI individuals included: (1) During the level walking, the affected side showed the similar pressure contribution as the unaffected side (P>0.05). While compared with healthy individuals, there was a significantly higher peak force in the 5th metatarsal area (t=-3.86, P=0.03) of the affected side, lower peak force in the 1st (t=2.99, P=0.02), 2nd metatarsal head areas (t=2.09, P=0.01) of the affected side, medial hindfoot areas of both sides (affected, t=2.33, P=0.01; unaffected, t=3.74, P=0.02) and toes areass of both sides (affected, t=2.23, P=0.01; unaffected, t=3.28, P=0.02) and a delay to peak force in the 4th metatarsal head area (t=3.33, P=0.01) of the affected side. (2) During the single leg standing, the CAI individuals showed significantly worse balance control in the anterior/posterior direction (P < 0.05) and lateral/medial direction (P < 0.05) compared with the healthy controls, and the affected side had more severe balance control deficit in the lateral/medial direction (P < 0.05). (3) The women (P < 0.05) and the individuals with higher Beighton scores (P < 0.05) showed worse balance control deficit in the lateral/medial direction. CONCLUSION CAI individuals showed significantly a more lateral shifted plantar distribution during the level walking compared with the healthy individuals and the tendency was worse on the affected sides, and showed worse balance control in the anterior/posterior direction and lateral/medial direction during the single leg standing. The women and those with generalized ligament laxity showed significantly worse balance control.
Ankle ; Ankle Joint ; Case-Control Studies ; Female ; Foot ; Humans ; Joint Instability

Objective: To conduct an ample review of the existing generic preference-based measures for health-related quality of life around the globe. Methods: Databases including PubMed，Embase，CNKI and WanFang Data, literature retrieval and information extraction were carried out on relevant studies of the universal health utility scale published until April 2020 worldwide，and all the existing generic health utility measures were identified. The original development articles included in the measures were further searched to extract the basic information of the measures，the conduction process，and the structure of the health state descriptive system. All of the dimensions included in the measures were summarized and analyzed from three aspects of physical (physiological)，mental (psychological)，and societal，respectively. Results: Through searching and screening，a total of 36 articles (both in Chinese and English literatures) were obtained, among which 18 generic preference-based measures were identified and 30 original search and development articles of these 18 measures were extracted. The number of dimensions of these 18 measures varied between the range of 3~15，the number of levels under each dimension ranged between 2 and 7，and the total number of health states that could be described by these measures amounted between 64 and 2.37 × 1023.The dimensions describing the physiological aspect in health were involved by all of 18 measures，while the dimensions describing psychological health and societal aspects in health were involved by only 16 and 10 measures，respectively. The physiological，psychological and societal dimensions included 10，4, and 5 specific categories，respectively. Two ways of conducting the health state descriptive system were identified, which were mainly based on the existing data and materials，and through the construction of the items pool combined with psychometric methods to determine the included dimensions of the measures. Conclusion :In recent years，more emphasis on the measurement of mental and societal health on the basis of physiological aspect was included in the newly developed measures，and the construction process of the health state descriptive system is becoming more and more standardized.

Bovine aortic endothelial cells (BAECs) were cultured with high glucose (33 mmol/L), 4 mg/L green tea polyphenols (GTPs) or 4 mg/L GTPs co-treatment with high glucose for 24 h in the presence or absence of Bafilomycin-A1 (BAF). We observed that high glucose increased the accumulation of LC3-II. Treatment with BAF did not further increase the accumulation of LC3-II. Results also showed an increased level of p62 and decreased Beclin-1. However, GTPs showed inversed trends of those proteins. Furthermore, GTPs co-treatment with high glucose decreased the level of LC3-II and a much higher accumulation of LC3-II was observed in the presence of BAF in comparison with high glucose alone. Results also showed a decreased p62 and increased Beclin-1. The results demonstrated that GTPs alleviated autophagy inhibition induced by high glucose, which may be involved in the endothelial protective effects of green tea against hyperglycemia.
Animals ; Autophagy ; drug effects ; Cattle ; Cells, Cultured ; Endothelial Cells ; drug effects ; metabolism ; Gene Expression Regulation ; drug effects ; Glucose ; toxicity ; Macrolides ; pharmacology ; Polyphenols ; chemistry ; pharmacology ; Tea ; chemistry

The combination therapy with daclatasvir and asunaprevir can achieve a high sustained viral response rate against hepatitis C virus (HCV) genotype 1, but so far this regimen has not been reported in the treatment of Chinese patients with chronic hepatitis C (CHC) genotype 1b. Here we report a case of CHC genotype 1b in a 44-year-old female chinese patient who was treated with this regimen for 24 weeks. The patient showed sustained viral response after the treatment and was clinically cured. During the treatment, the patient experienced a transient elevation of serum total bilirubin accompanied by lowered hemoglobin fluctuating between 100 and 110 g/L.
Adult ; Antiviral Agents ; therapeutic use ; Female ; Genotype ; Hepacivirus ; genetics ; Hepatitis C, Chronic ; drug therapy ; Humans ; Imidazoles ; therapeutic use ; Isoquinolines ; therapeutic use ; Sulfonamides ; therapeutic use

BACKGROUNDChronic obstructive pulmonary disease (COPD) has a variable natural history and not all individuals follow the same course. This study aimed to identify the prevalence and characteristics of asymptomatic COPD patients from a population-based survey in China.

METHODSA multistage cluster sampling strategy was used in a population from seven different provinces/cities. All residents (over 40 years old) were interviewed with a standardized questionnaire and spirometry. Post-bronchodilator forced expiratory volume in 1 second (FEV(1))/forced vital capacity (FVC) of less than 70% was defined as the diagnostic criterion of COPD. All COPD patients screened were divided into symptomatic group and asymptomatic group according to the presence or absence of chronic respiratory symptoms. Socio-demographic, personal and exposure variables were collected and analyzed.

RESULTSAmong the 1668 patients who were diagnosed with COPD from the 25 627 sampling subjects, 589 (35.3%) were asymptomatic. The age, sex, body mass index (BMI), rural and urban distributions, smoking habit and education levels were similar in the two groups. A total of 64.7% of the asymptomatic patients had no comorbidities. Cardiovascular diseases and lung cancer were more common among symptomatic COPD patients than asymptomatic group. Asymptomatic COPD group were less likely to present with poor ventilation in the kitchen, a family history of respiratory disease and recurrent childhood cough. Asymptomatic COPD patients had significantly higher FEV(1) (73.1% vs. 61.0%), FVC (91.9% vs. 82.0%), and a higher ratio of FEV(1)/FVC (62.9% vs. 58.7%) (all P < 0.001) than symptomatic group. More asymptomatic patients were underdiagnosed (91.9% vs. 54.3%, P < 0.001) than symptomatic patients.

CONCLUSIONSThis large population-based survey confirmed a high prevalence of asymptomatic COPD patients in China. More use of spirometry screening test may be important to the early detection of COPD.

Adult ; Aged ; Aged, 80 and over ; China ; epidemiology ; Educational Status ; Female ; Humans ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; diagnosis ; epidemiology ; Risk Factors ; Smoking ; Spirometry ; Surveys and Questionnaires