To explore the inhibitory effect of ginkgolide B (GB) on MH7A human fibroblast-like synoviocytes (FLS) and its potential mechanism. Firstly, 20 μg/L tumor necrosis factor-α (TNF-α) was pretreated with MH7A to establish a cell model of arthritis. After incubation of MH7A cells with various concentrations of GB, CCK-8 assay, Transwell assay, and flow cytometry (FCM) were separately used to detect cell viability, cell invasion, and cell apoptosis rate and cell cycle; Real-time quantitative PCR and Western blot assay were performed to detect the apoptosis- and cycle-related gene transcriptions and protein expressions, respectively. The results showed that compared with the control group, GB dose- and time-dependently suppressed cell viability to a greater extent; GB significantly reduced cell invasive ability and increased cell apoptosis rate and proportion of G0/G1 phase in MH7A cells, along with increased transcription levels of Bcl-2-associated X protein (Bax) and p21 mRNA and decreased transcription levels of Bcl-2, myeloid cell leukemia 1(Mcl-1), protein kinase B (PKB; AKT), IP3K, Cyclin D1 and cyclin-dependent kinase 4 (CDK4) mRNA; GB remarkably increased expression levels of Bax, p21, and cleaved-Caspase 3 protein and decreased expression levels of Bcl-2, Mcl-1, p-AKT, p-PI3K, Cyclin D1, and CDK4 protein, with decreased ratios of p-PI3K/PI3K, p-AKT/AKT, and Bcl-2/Bax. In conclusion, GB blocks the G1-to-S cell cycle transition, suppresses cell viability and cell invasion and induces cell apoptosis of MH7A human RA-FLS via suppressing the PI3K/AKT signaling pathway.

Objective:To study the correlation between serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and echocardiographic parameters in patients with chronic Keshan disease, providing reference for diagnosis and prognosis evaluation of chronic Keshan disease.Methods:Ninety-nine patients with chronic Keshan disease who received standardized treatment at Jingchuan County People's Hospital in Pingliang City, Gansu Province from January to December 2020 were selected. Among them, 16 patients were classified as cardiac function grade Ⅱ according to New York Heart Association (NYHA), 69 as grade Ⅲ and 14 as grade Ⅳ. The patients underwent echocardiography and their serum NT-proBNP level was measured using fluorescence immunochromatography. The differences in serum NT-proBNP levels among patients with different cardiac function grades were compared, and the correlation between cardiac function grades, serum NT-proBNP level and echocardiographic parameters was analyzed.Results:The serum NT-proBNP levels in patients with cardiac function grades Ⅱ, Ⅲ, and Ⅳ were (1 107.26 ± 268.03), (2 125.98 ± 293.02), and (8 268.59 ± 2 659.50) pg/ml, respectively. The differences among the three groups were statistically significant ( F = 13.94, P < 0.001). The serum NT-proBNP level was positively correlated with cardiac function grades ( r = 0.44, P < 0.001), left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and left atrial diameter ( r = 0.45, 0.52, 0.38, P < 0.001), and negatively correlated with fractional shortening and left ventricular ejection fraction ( r = - 0.39, - 0.46, P < 0.001). Conclusions:The serum NT-proBNP level in patients with chronic Keshan disease with different cardiac function grades is different, and is positively correlated with echocardiographic parameters reflecting the degree of cardiac structural and functional impairment. The NT-proBNP level may become an early diagnostic, grading, and prognostic indicator for chronic Keshan disease.

Objective:To analyze the association between waist circumference (WC) and ischemic stroke (IS).Methods:The data for the present study were from the prospective cohort study of China Kadoorie Biobank in Qingdao. Using baseline information and IS events of the participants, the Cox proportional hazard regression model and restricted cubic spline (RCS) were used to analyze the association between WC and IS.Results:A total of 33 355 participants were included in the study, with 302 008.88 person-years of follow-up. A total of 1 093 new cases of IS were observed. Multivariate Cox proportional hazard regression model analysis showed that compared to the respondents with normal WC (male <85.0 cm, female <80.0 cm), respondents with excessive WC (male ≥85.0 cm, female ≥80.0 cm) had a 78% higher risk of IS incidence [hazard ratio( HR)=1.78, 95% CI: 1.51-2.10], and the risk increased by 72% ( HR=1.72, 95% CI: 1.40-2.12) and 83% ( HR=1.83, 95% CI: 1.40-2.39) in men and women. According to the RCS, the increase in WC and the risk of IS showed an "S" trend of nonlinear dose-response relationship. Conclusions:The risk of IS would increase with the WC. Keeping a normal WC is important for preventing IS.

30 patients with chronic periodontitis and Type 2 diabetes mellituse were included.By a split-mouth design,the teeth in the left side were served as the experiment group and given Nd∶YAG and Er∶YAG laser therapy adjunctive to conventional periodontal treatment;the teeth in the right side were served as the control group and given conventional periodontal treatment alone.Before and after treatment perio-dontal and CBCT image indexes were examinde and compare between the 2 groups.Before treatment all the indexes were not statistically dif-ferent between the 2 groups(P＞0.05).3 months after treatment,the bleeding index(BI)and probing depth(PD)of the experimental group were significantly lower than those of the control group(P＜0.05).6 months after treatment,BI,PD and attachment loss(AL)in the experi-mental group were significantly lower than those in the control group,and the surface area and volume of the root in the alveolar bone were significantly higher than those in the control group(P＜0.05).Nd∶YAG and Er∶YAG laser therapy adjunctive to conventional periodontal treatment is more effective than conventional periodontal treatment alone in the treatment of chronic periodontitis with type 2 diabetes melli-tus.

Objective To investigate the effect of Huangzhi oral liquid on ferroptosis and apoptosis of hepatocytes in acute hyperlipidemia mice based on abnormal lipid metabolism.Methods Forty SPF grade C57BL/6 mice were randomly assigned to the normal control group,the model group,Huangzhi oral liquid low-dose and high-dose groups,and fenofibrate group,with 8 mice in each group.All administration groups were given Huangzhi oral liquid and fenofibrate by gavage at corresponding doses,while the normal control group and the model group were given the same dose of distilled water for a period of 5 days.on the third day of administration,in addition to the normal control group,other groups were injected intramuscularly with Triton WR-1339 to establish a hyperlipidemia model.After the administration,the serum lipid levels and liver function in mice were detected.The pathological changes of liver were observed by HE staining and lipid accumulation was observed by oil red O staining.The iron content in liver tissues was detected by tissue iron assay kit.The changes in protein expression of ABCA1,ABCG5,LXRα,ASGR1,cleaved-PARP,cleaved-caspase 3,Bcl2,Bax,TFR1,SLC7A11,GCLM,GPX4 and FTH1 in liver were detected by Western Blot.Results Compared with the model group,Huangzhi oral liquid could reduce the lipid vacuoles in liver tissues,alleviate the degree of lipid degeneration,reduce the content of TC,TG,LDL-C,AST and ALT in serum,increase the content of HDL-C,increase the protein expression levels of ABCA1,ABCG5,LXRα,Bcl-2,SLC7A11,GCLM,GPX4 and FTH1 in mice liver tissues,reduce the protein expression levels of ASGR1,cleaved-PARP,cleaved-caspase 3,Bax and TFR1.Conclusion Huangzhi oral liquid can alleviate the abnormal lipid metabolism in acute hyperlipidemia mice,thus alleviates hepatocyte apoptosis and ferroptosis.

Objective:To analyze the research hotspots and trends in the field of Traditional Chinese Medicine (TCM) for cervical cancer at home and abroad in recent 30 years through visualization method.Methods:By setting "cervical cancer" and "TCM" as the research subjects, the articles were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, and Web of Science Core database (WoS) from January 1, 1992 to January 1, 2022. Citespace 5.8 R3 software was used to conduct visual analysis on the authors, institutions and keywords included in the articles.Results:A total of 1 123 Chinese articles and 573 English articles were included. The number of articles issued showed a gradual upward trend; the author with the largest number of Chinese publications was Jin Zhe, and the author with the largest number of English publications was Chen Guo. The institution with the largest number of Chinese publications was Beijing University of Chinese Medicine; the institution with the largest number of English publications was Chinese Academy of Medical Sciences. Keywords co-occurrence of the top 3 Chinese keywords in the network frequency (excluding the search words) were "cervical erosion", "urinary retention" and "Yunnan Baiyao"; English keywords were "HeLa cell", "bibliometric", and "information monitoring system". Chinese keywords formed 11 clusters and 25 emergent words; English keywords formed 9 clusters and 17 emergent words.Conclusions:The research content in the field of TCM of cervical cancer about knowledge map in the past 30 years at home and abroad is rich. TCM can play the role of antagonizing human papillomavirus, enhancing immune function, regulating TCM constitution, improving quality of life and so on. At present, the research hotspot is the mechanism exploration of cervical cancer and the curative effect research of clinical complications, and the research trend is clinical curative effect research.

As a malleable and novel tool for antigen recognition and modulation, nanobodies have the advantages of small size, easiness of expression, screening and modification, as well as high affinity and stability. Nanobodies are capable of recognizing more cryptic antigenic epitopes that are difficult to be recognized by traditional antibodies, making them increasingly used in the diagnosis and treatment of various diseases and assays. Nanobodies are also playing an irreplaceable role in the basic research. This review summarized the recent development of nanobodies and their derivatives in the detection of small molecules, pathogenic microorganisms and diagnosis of diseases, as well as in the fields of targeted therapies, cellular and molecular imaging. Broad prospects of nanobodies in the field of protein conformation studies were also reviewed.
Single-Domain Antibodies

Objective To analyze the clinical significance of endometrial abnormalities in patients with breast cancer after oral administration of tamoxifen, and to determine the risk factors for endometrial malignancy. Methods We collected data from 135 patients with breast cancer who underwent surgery for endometrial abnormalities after oral administration of tamoxifen at the Department of Gynecology from September 2011 to December 2017. According to the pathological results obtained, the patients were divided into groups A (benign endometrial lesion) and B (precancerous and malignant endometrial lesion). The relationships between endometrial malignancy and factors including age, menopausal status, body mass index, endometrial thickness, abnormal uterine bleeding, oral dose of tamoxifen, duration of oral medication, and complications (hypertension and diabetes) were compared between the groups. Results There were 124 patients in group A and 11 patients in group B. The difference in the incidence of abnormal uterine bleeding, which was a risk factor for endometrial malignancy, was significant different between the groups (P ＜ 0.05). Conclusion Physicians should pay close attention to abnormal uterine bleeding in patients taking tamoxifen after surgery for breast cancer. Hysteroscopy should be used to confirm the nature of lesions, and patients without symptoms should be followed up.

Endometrial cancer is a common malignancy of the female reproductive system. Despite improvement in living standards, the incidence of endometrial cancer is increasing due to the lack of effective screening. Early detection of endometrial cancer and precancerous lesions can significantly improve prognosis and survival. At present, China lacks a method for screening endometrial lesions comparable to that for cervical cancer screening. A recently introduced endometrial sampler has the advantages of simple operation, low cost, and minimal trauma, and is gradually being accepted for clinical screening of endometrial cancer and precancerous lesions in other countries.This study aims to explore current screening methods for endometrial cancer and precancerous lesions and the clinical application of an endometrial sampler for screening.

Tumor-derived exosomes (TEXs) are small membrane vesicles secreted by tumor cells.They contain various proteins and RNA which make they serve as functional mediators in cell interaction.TEXs can alter the components of extracellular matrix and induces epithelial-mesenchymal transition of tumor cells,which enhance the invasiveness of tumor cells.TEXs regulate immunity through multiple pathways,allowing circulating tumor cells to escape immune surveillance.TEXs promote pre-metastatic microenvironment in target organ before metastasis and induce angiogenesis after circulating tumor cells colonization.Understanding the role and mechanism of TEXs in this process can effectively block relevant signaling pathways which may provide new targeted therapies for clinic.