Effect of quercetin's anti-breast cancer depending on presence of estrogen receptor via down-regulating long non-coding RNA MALAT-1 and its mechanism / 中国药理学通报

Aim To investigate the molecular mechanism by which quercetin inhibits the malignant behavior of breast cancer cells. Methods Breast cancer cell lines MCF-7 and MB231 were used as the research models. Lentiviral transfection was employed to establish tumor cells with high expression of ERa and MAL-AT-1. The expression of MALAT-1 was assessed using RT-qPCR,and ERa expression was determined through Western blot. Subsequently, CCK-8 assay and colony formation assay were conducted to evaluate cell proliferation. PI staining and adenovirus transfection were performed to observe the inhibitory effects of quercetin on breast cancer cell proliferation. Results 17|3-es-tradiol ( E2 ) promoted the proliferation of MCF-7 breast cancer cells, while 5 jjunol L quercetin reversed the promoting effect of E2 on proliferation ( P 0. 05 ) . Quercetin had no effect on MB231 breast cancer cells. Overexpression of ERa significantly inhibited the pro-proliferative effect of E2 on MB231-ERa cells, and quercetin further suppressed this effect. Additionally , quercetin inhibited the expression of MALAT-1. However,this inhibitory effect was reversed by overexpression of MALAT-1, leading to enhanced cell proliferation , cell cycle progression, and clonal formation a-bility. Conclusions Quercetin exerts its anti-tumor effects on breast cancer cells by regulating MALAT-1, dependent on the presence of estrogen receptor. Quercetin shows potential as a therapeutic drug for breast cancer targeting the estrogen receptor.

Comparison of clinical features and outcomes of proliferative, fibrotic, and mixed subtypes of IgG4-related disease: A retrospective cohort study / 中华医学杂志(英文版)

BACKGROUND@#Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized immune-mediated disorder that can affect almost any organ in the human body. IgG4-RD can be categorized into proliferative and fibrotic subtypes based on patients' clinicopathological characteristics. This study aimed to compare the clinical manifestations, laboratory findings, and treatment outcomes of IgG4-RD among different subtypes.@*METHODS@#We prospectively enrolled 622 patients with newly diagnosed IgG4-RD at Peking Union Medical College Hospital from March 2011 to August 2021. The patients were divided into three groups according to their clinicopathological characteristics: proliferative, fibrotic, and mixed subtypes. We compared demographic features, clinical manifestations, organ involvement, laboratory tests, and treatment agents across three subtypes. We then assessed the differences in treatment outcomes among 448 patients receiving glucocorticoids alone or in combination with immunosuppressants. Moreover, risk factors of relapse were revealed by applying the univariate and multivariate Cox regression analysis.@*RESULTS@#We classified the 622 patients into three groups consisting of 470 proliferative patients, 55 fibrotic patients, and 97 mixed patients, respectively. We found that gender distribution, age, disease duration, and frequency of allergy history were significantly different among subgroups. In terms of organ involvement, submandibular and lacrimal glands were frequently involved in the proliferative subtype, while retroperitoneum was the most commonly involved site in both fibrotic subtype and mixed subtype. The comparison of laboratory tests revealed that eosinophils ( P = 0.010), total IgE ( P = 0.006), high-sensitivity C-reactive protein ( P <0.001), erythrocyte sedimentation rate ( P <0.001), complement C4 ( P <0.001), IgG ( P = 0.001), IgG1 (P <0.001), IgG4 (P <0.001), and IgA ( P <0.001), at baseline were significantly different among three subtypes. Compared with proliferative and mixed subtypes, the fibrotic subtype showed the lowest rate of relapse (log-rank P = 0.014).@*CONCLUSIONS@#Our study revealed the differences in demographic characteristics, clinical manifestations, organ involvement, laboratory tests, treatment agents, and outcomes across proliferative, fibrotic, and mixed subtypes in the retrospective cohort study. Given significant differences in relapse-free survival among the three subtypes, treatment regimens, and follow-up frequency should be considered separately according to different subtypes.

Systematic review and Meta-analysis of Gusongbao preparation in treatment of primary osteoporosis / 中国中药杂志

This study aims to provide evidence for clinical practice by systematically reviewing the efficacy and safety of Gusongbao preparation in the treatment of primary osteoporosis(POP). The relevant papers were retrieved from four Chinese academic journal databases and four English academic journal databases(from inception to May 31, 2022). The randomized controlled trial(RCT) of Gusongbao preparation in the treatment of POP was included after screening according to the inclusion and exclusion criteria. The quality of articles was evaluated using risk assessment tools, and the extracted data were subjected to Meta-analysis in RevMan 5.3. A total of 657 articles were retrieved, in which 15 articles were included in this study, which involved 16 RCTs. A total of 3 292 patients(1 071 in the observation group and 2 221 in the control group) were included in this study. In the treatment of POP, Gusongbao preparation+conventional treatment was superior to conventional treatment alone in terms of increasing lumbar spine(L2-L4) bone mineral density(MD=0.03, 95%CI[0.02, 0.04], P<0.000 01) and femoral neck bone mineral density, reducing low back pain(MD=-1.69, 95%CI[-2.46,-0.92], P<0.000 1) and improving clinical efficacy(RR=1.36, 95%CI[1.21, 1.53], P<0.000 01). Gusongbao preparation was comparable to similar Chinese patent medicines in terms of improving clinical efficacy(RR=0.95, 95%CI[0.86, 1.04], P=0.23). Gusongbao preparation was inferior to similar Chinese patent medicines in reducing traditional Chinese medicine syndrome scores(MD=1.08, 95%CI[0.44, 1.71], P=0.000 9) and improving Chinese medicine syndrome efficacy(RR=0.89, 95%CI[0.83, 0.95], P=0.000 4). The incidence of adverse reactions of Gusongbao preparation alone or combined with conventio-nal treatment was comparable to that of similar Chinese patent medicines(RR=0.98, 95%CI[0.57, 1.69], P=0.94) or conventio-nal treatment(RR=0.73, 95%CI[0.38, 1.42], P=0.35), and the adverse reactions were mainly gastrointestinal discomforts. According to the available data, Gusongbao preparation combined with conventional treatment is more effective than conventional treatment alone in increasing lumbar spine(L2-L4) bone mineral density and femoral neck bone mineral density, reducing low back pain, and improving clinical efficacy. The adverse reactions of Gusongbao preparation were mainly gastrointestinal discomforts, which were mild.

Progressin Tumor-Associated Macrophages in the Treatment of Pancreatic Cancer / 中国医学科学院学报

Pancreatic cancer is one of the digestive system tumors with a high degree of malignancy,and most of the patients are diagnosed in advanced stages.Because of limited available therapies,the mortality of this disease remains high.Tumor-associated macrophages(TAM),the main immune cells in the tumor microenvironment,are involved in the regulation of the occurrence and development of pancreatic cancer.Specifically,TAM are involved in the proliferation,invasion,immune escape,and chemoresistance of pancreatic cancer cells,demonstrating potential in the targeted therapy of pancreatic cancer.In this paper,we summarize the TAM-based therapies including consuming TAM,reprogramming TAM,dynamic imaging of TAM with nanoprobes,and regulating the phagocytic ability of TAM for pancreatic cancer,aiming to provide a theoretical basis for developing new therapies for pancreatic cancer.

Genetic analysis of novel pathogenic gene HROB in a family with primary ovarian insufficiency / 浙江大学学报·医学版

A 13-year and 6-month-old girl attended the Hunan Children's Hospital due to delayed menarche. The laboratory test results indicated increased follicle-stimulating hormone and luteinizing hormone, decreased anti-Mullerian hormone, and pelvic ultrasound showed a cord-like uterus and absence of bilateral ovaries. Her 11-year and 5-month-old younger sister had the same laboratory and imaging findings, and both girls were diagnosed with primary ovarian insufficiency. Whole exome sequencing and Sanger sequencing confirmed that the proband and her sister carried heterozygous variants of HROB gene c.718C>T (p.Arg240*) and c.1351C>T (p.Arg451*), which were inherited from their parents respectively and consistent with autosomal recessive inheritance. Oral estradiol valerate at an initial dose of 0.125 mg/d was given to the proband, and the secondary sexual characteristics began to develop after 6 months.

Research progress on biocomposites based on bioactive glass / 生物医学工程学杂志

Bioactive glass (BG) has been widely used in the preparation of artificial bone scaffolds due to its excellent biological properties and non-cytotoxicity, which can promote bone and soft tissue regeneration. However, due to the brittleness, poor mechanical strength, easy agglomeration and uncontrollable structure of glass material, its application in various fields is limited. In this regard, most current researches mainly focus on mixing BG with organic or inorganic materials by freeze-drying method, sol-gel method, etc., to improve its mechanical properties and brittleness, so as to increase its clinical application and expand its application field. This review introduces the combination of BG with natural organic materials, metallic materials and non-metallic materials, and demonstrates the latest technology and future prospects of BG composite materials through the development of scaffolds, injectable fillers, membranes, hydrogels and coatings. The previous studies show that the addition of BG improves the mechanical properties, biological activity and regeneration potential of the composites, and broadens the application of BG in the field of bone tissue engineering. By reviewing the recent BG researches on bone regeneration, the research potential of new materials is demonstrated, in order to provide a reference for future related research.

Screening of quality markers and activity verification of Glycyrrhizae Radix et Rhizoma based on small molecule compound-protein interaction / 中国中药杂志

In order to solve the problem of weak correlation between quality control components and efficacy of Glycyrrhizae Radix et Rhizoma, this study detected the interaction between small molecular chemical components of Glycyrrhizae Radix et Rhizoma and total proteins of various organs of mice by fluorescence quenching method to screen potential active components. The 27 chemical components in Glycyrrhizae Radix et Rhizoma were detected by HPLC and their deletion rates in 34 batches of Glycyrrhizae Radix et Rhizoma were calculated. Combined with the principle of component effectiveness and measurability, the potential quality markers(Q-markers) of Glycyrrhizae Radix et Rhizoma were screened. RAW264.7 macrophage injury model was induced by microplastics. The cell viability and nitric oxide content were detected by CCK-8 and Griess methods. The levels of inflammatory factors(TNF-α, IL-1β, IL-6, CRP) and oxidative stress markers(SOD, MDA, GSH) were detected by the ELISA method to verify the activity of Q-markers. It was found that the interaction strength between different chemical components and organ proteins in Glycyrrhizae Radix et Rhizoma was different, reflecting different organ selectivity and 18 active components were screened out. Combined with the signal-to-noise ratio of the HPLC chromatographic peaks and between-run stability of the components, seven chemical components such as liquiritin apioside, liquiritin, isoliquiritin apioside, isoliquiritin, liquiritigenin, isoliquiritigenin and ammonium glycyrrhizinate were finally screened as potential Q-markers of Glycyrrhizae Radix et Rhizoma. In vitro experiments showed that Q-markers of Glycyrrhizae Radix et Rhizoma could dose-dependently alleviate RAW264.7 cell damage induced by microplastics, inhibit the secretion of inflammatory factors, and reduce oxidative stress. Under the same total dose, the combination of various chemical components could synergistically enhance anti-inflammatory and antioxidant effects compared with the single use. This study identified Q-markers related to the anti-inflammatory and antioxidant effects of Glycyrrhizae Radix et Rhizoma, which can provide a reference for improving the quality control standards of Glycyrrhizae Radix et Rhizoma.

Assessment of adequacy of colonoscopic bowel preparation based on nomogram visualization / 中华消化内镜杂志

Objective:To establish a nomogram to evaluate the adequacy of bowel preparation before colonoscopy and to guide clinical decision-making.Methods:A total of 1 023 valid questionnaires from subjects who underwent diagnosis and treatment of colonoscopy at the digestive endoscopy center, Xiangya Hospital, Central South University from September 2020 to March 2021 were finally returned. The contents of the questionnaire mainly included the clinical characteristics, defecation habits, the number of defecation and the time of the last defecation after taking the medicine and the self-assessment results of bowel preparation before colonoscopy. Subjects' bowel preparation was graded with the Boston bowel preparation scale (BBPS) by a designated endoscopist in a single blinded method. Multivariate analyse was used to explore the influencing factors for bowel preparation adequacy, and a nomogram was drawn accordingly.Results:Based on BBPS scores, bowel preparation of 674 subjects were adequate and 349 were inadequate. Multivariate analyse identified the number of defecation per week ( OR=1.649,95% CI:1.233-2.204, P=0.001), the number of defecation after medication ( OR=3.963, 95% CI: 1.851-8.485, P<0.001), the time of the last defecation after medication ( OR=5.151, 95% CI: 1.152-23.037, P=0.032), and self-assessment of bowel preparation before examination ( OR=8.284, 95% CI: 2.042-33.601, P=0.003) were influencing factors for the adequacy of bowel preparation for colonoscopy. The area under the receiver operating characteristic curve of assessment of colonoscopic bowel preparation adequacy with nomogram visualization according to influencing factors was 0.913, optimal cutoff value was 0.824, the sensitivity was 0.746, and the specificity was 0.971 under the internal validation cohort. Conclusion:The nomogram based on the number of defecation per week, the number of defecation after medication, the time of the last defecation after medication, and self-assessment of bowel preparation before examination could evaluate the adequacy of bowel preparation before colonoscopy, which is worthy of application.

The interaction between social psychology and workload factors of neck work-related musculoskeletal disorders / 中国职业医学

{L-End}Objective To explore the interaction between social psychology and workload factors on neck work-related musculoskeletal disorders (WMSDs) in manual workers. {L-End}Methods Manual workers in Henan Province and Hubei Province were selected as the research subjects using typical sampling method. The Chinese Musculoskeletal Questionnaire was used to investigate the prevalence of neck WMSDs in the research subjects. A total of 4 327 workers with neck WMSDs were selected as the case group, and 4 327 workers without neck WMSDs were selected as the control group in a 1∶1 pairing. Conditional logistic regression analysis was used to compare the relevant risk factors in the two groups, and the additive interaction model was established to analyze the interactions between the risk factors. {L-End}Results The univariate conditional logistic analysis results showed that dynamic load, static load, power load and psychosocial factors increased the risk of neck WMSDs in manual workers (all P<0.05). In terms of the social psychological factors, insufficient rest time had the greatest impact workers, with the odds ratio (OR) and 95% confidence interval (CI) of 1.799 (1.647-1.965). In terms of dynamic load, static load and power load, repeated similar movements of the head per minute (bending, twisting), forward bending of the neck or maintaining this posture for a long time, and lifting heavy objects>20 kg had the greatest impact, with the OR and 95%CI of 1.599 (1.470-1.739), 1.984 (1.805-2.181) and 1.241 (1.093-1.408), respectively. There was a synergistic interaction between insufficient rest time and forward bending of the neck or maintaining this posture for a long time, and the relative excess risk due to interaction (95%CI) and attributable proportion (95%CI) were 0.420 (0.187-0.652) and 0.171 (0.066-0.276), respectively. There is no interaction between insufficient rest time and repeated similar movements of the head per minute (bending, twisting), and lifting heavy objects >20 kg. {L-End}Conclusion The interaction between insufficient rest time and forward bending of the neck or maintaining this posture for a long time (static load) can increase the risk of neck WMSDs in manual workers, which is an additive synergistic effect.

Establishment and Evaluation of Heart Failure Model with Qi Deficiency Syndrome / 中国实验方剂学杂志

ObjectiveTo establish and evaluate a mouse model of heart failure with Qi deficiency syndrome. MethodForty-four KM mice were randomly divided into sham operation group， model group， and modified Si Junzitang group （12.89 g·kg-1）. The model group and the modified Si Junzitang group underwent thoracic aortic constriction （TAC）， while the sham operation group only underwent suture without constriction. Echocardiography and pathological examination were used to assess the heart failure model and evaluate the pharmacological effects. Macroscopic characterization， microscopic biology， and formula identification were conducted to collect general signs， body weight， open-field behavior， grip strength， mitochondrial ultrastructure， and other macroscopic and microscopic characteristics of mice. Mitochondrial fission and fusion protein expression were measured to determine the syndrome type. ResultEight weeks after TAC， compared with the sham operation group， the model group showed a significant decrease in left ventricular ejection fraction （LVEF） （P<0.01）， and modified Si Junzitang improved LVEF in mice （P<0.05）. Hematoxylin-eosin （HE） staining of the heart showed inflammatory cell infiltration and thickening of blood vessel walls in the model group， which was significantly improved by modified Si Junzitang. After 6-8 weeks， compared with the sham operation group and the modified Si Junzitang group， the model group exhibited significant hair loss， hair yellowing， decreased activity， and depression. Moreover， compared with the sham operation group， the model group had a significantly lower increase in body weight （P<0.05）， while the modified Si Junzitang group showed a significant increase in body weight （P<0.05） compared with the model group. After 6-8 weeks， compared with the sham operation group， the model group showed a significant decrease in open-field distance and speed （P<0.05）， while the modified Si Junzitang group exhibited significantly improved open-field distance and speed in the 8th week （P<0.05）. After 6-8 weeks， compared with the sham operation group， the model group exhibited a significant decrease in maximum grip strength （P<0.05）， while the modified Si Junzitang group showed a significant increase in maximum grip strength 8 weeks after TAC （P<0.05）. Transmission electron microscopy of the gastrocnemius muscle showed uneven muscle tissue matrix， mitochondrial swelling， increased volume， matrix dissolution， ridge loss， and vacuolization in the model group， while modified Si Junzitang improved mitochondrial swelling， ridge fracture， and matrix vacuolization. Western blot analysis showed that the expression of the kinetic associated protein 1 （DRP1） in the gastrocnemius muscle of the model group significantly increased （P<0.01）， and the expression of mitochondrial fusion hormone 1 （MFN1） significantly decreased （P<0.05） as compared with those in the sham operation group. Furthermore， compared with the model group， the modified Si Junzitang group exhibited a significant decrease in the expression of DRP1 （P<0.05） and a significant increase in MFN1 expression （P<0.01）. ConclusionMice exhibited significant manifestations of qi deficiency syndrome 6-8 weeks after TAC， accompanied by abnormal mitochondrial morphology and function in the gastrocnemius muscle， which were significantly improved by modified Si Junzitang.

Plumbagin Induces Ferroptosis Through Nrf-2/Keap1 Signaling Pathway in Bladder Cancer Cells / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of plumbagin as a novel ferroptosis inducer in bladder cancer inhibition. MethodBladder cancer T24 cells were used in this study. The effect of different concentrations of plumbagin （0.1， 1， 2， 3， 6， 12， 24， 48 μmol·L-1） on the viability of T24 cells was detected by cell counting kit-8 （CCK-8）. The effect of different concentrations of plumbagin （1.5， 3， 6 μmol·L-1） on the apoptosis of T24 cells was detected by annexin V-fluorescein isothiocyanate （Annexin V FITC）/PI apoptosis kit. Different inhibitors （ferroptosis inhibitor Fer-1， apoptosis inhibitor VAD， and necroptosis inhibitor Nec-1） were used in combination with plumbagin （6 μmol·L-1）. Reactive oxygen species （ROS） fluorescent probe （DCFH-DA）， malonaldehyde （MDA）， and glutathione （GSH） kits were used to detect the effects of different concentrations of plumbagin （1.5， 3， 6 μmol·L-1） on the level of ROS and the content of MDA and GSH in T24 cells， respectively. The effect of different concentrations of plumbagin （1.5， 3， 6 μmol·L-1） on peroxide levels in T24 cells was detected by C11-BODIPY fluorescent probe. Western blot was used to detect the effect of different concentrations of plumbagin （1.5， 3， 6 μmol·L-1） on the protein expression of solute carrier family 7 member 11 （SLC7A11）， glutathione peroxidase 4 （GPX4）， nuclear factor E2-related factor-2 （Nrf-2）， and Kelch-like ECH-associated protein 1 （Keap1）. ResultCompared with the blank group， plumbagin could inhibit the activity of T24 cells （P<0.05） with IC50 of 3.52 μmol·L-1. At the concentrations of 1.5， 3， 6 μmol·L-1， plumbagin significantly promoted the apoptosis of T24 cells （P<0.05） as compared with the blank group. Compared with the plumbagin group at 6 μmol·L-1， the ferroptosis inhibitor and apoptosis inhibitor groups could reverse the inhibitory effect of 6 μmol·L-1 plumbagin on the proliferation of T24 cells （P<0.05）. Compared with the blank group， the plumbagin groups at 1.5， 3， 6 μmol·L-1 showed increased content of ROS， MDA， and lipid peroxides in T24 cells， decreased GSH level， and reduced SLC7A11， GPX4， and Nrf-2/Keap1 （P<0.05）. Conclusionplumbagin can induce ferroptosis， and its mechanism is related to the Nrf-2/Keap1 signaling pathway.

Topoisomerase Ⅱα Gene as a Marker for Prognostic Prediction of Hepatocellular Carcinoma: A Bioinformatics Analysis / 中国医学科学杂志(英文版)

Objective To investigate the expression of topoisomeraseⅡα (TOP2α) in hepatocellular carcinoma (HCC) and its role in predicting prognosis of HCC patients. Methods We used HCC-related datasets in UALCAN, HCCDB, and cBioPortal databases to analyze the expression and mutation of TOP2α and its co-expressed genes in HCC tissues. GO function and KEGG pathway enrichment of TOP2α and its co-expressed genes were identified. The TIMER database was used to analyze infiltration levels of immune cells in HCC. The impacts of TOP2α and its co-expression genes and the infiltrated immune cells on the survival of HCC patients were assayed by Kaplan-Meier plotter analysis. Results TOP2α and its co-expression genes were highly expressed in HCC (P< 0.001) and detrimental to overall survival of HCC patients (P< 0.001). TOP2α and its co-expression genes were mainly involved in cell mitosis and proliferation, and cell cycle pathway (ID: hsa04110, P = 0.001945). TOP2α and its co-expression genes were mutated in HCC and the mutations were significantly detrimental to overall survival (P = 0.0247) and disease-free survival (P = 0.0265) of HCC patients. High TOP2α expression was positively correlated with the infiltration of B cell (r = 0.459, P< 0.01), CD8+ T cell (r = 0.312, P< 0.01), CD4+ T cell (r = 0.370, P< 0.01), macrophage (r = 0.459, P< 0.01), neutrophil (r = 0.405, P< 0.01), and dendritic cell (r = 0.473, P< 0.01) in HCC. The CD8+ T cell infiltration significantly prolonged the 3- and 5-year survival of HCC patients (all P< 0.05), and CD4+ T cell infiltration significantly shortened the 3-, 5-, and 10-year survival of HCC patients (all P< 0.05). ConclusionTOP2α may be an oncogene, which was associated with poor prognosis of HCC patients and could be used as a biomarker for the prognostic prediction of HCC.

Polyhydroxylated eudesmane sesquiterpenoids and sesquiterpenoid glucoside from the flower buds of Tussilago farfara / 中国天然药物

Chemical fractionation of the n-BuOH partition, which was generated from the EtOH extract of the flower buds of Tussilago farfara, afforded a series of polar constituents including four new sesquiterpenoids (1-4), one new sesquiterpenoid glucoside (5) and one known analogue (6) of the eudesmane type, as well as five known quinic acid derivatives (7-11). Structures of the new compounds were unambiguously characterized by detailed spectroscopic analyses, with their absolute configurations being established by X-ray crystallography, electronic circular dichroism (ECD) calculation and induced ECD experiments. The inhibitory effect of all the isolates against LPS-induced NO production in murine RAW264.7 macrophages was evaluated, with isochlorogenic acid A (7) showing significant inhibitory activity.

Bioaccessibility analysis of active components in Salvia miltiorrhiza / 药学学报

In this study, a method for simultaneous quantitative analysis of 6 salvianolic acids and 4 tanshinones in extracts of Salviae Miltiorrhizae Radix et Rhizoma was established by ultra-high performance liquid chromatography (UHPLC). The semi-biomimetic method was applied to simulate digestion process in vitro, to explore the digestion and transport characters of oral administration through the gastrointestinal tract, and to explain the content ratio changes and bioaccessibility of active ingredients in Salviae Miltiorrhizae Radix et Rhizoma. The results showed that the 10 index components have a good linear relationship in the corresponding concentration range, and the average recovery rate was 91.35% to 105.65%. After simulated digestion in vitro, types of chemical composition in simulated gastric fluid and simulated intestinal fluid digested extracts of Salviae Miltiorrhizae Radix et Rhizoma did not change significantly. While the content ratio of salvianolic acid B and rosmarinic acid decreased, and the content ratio of protocatechuic aldehyde and danshensu increased. In the simulated gastric fluid digestion extract of Salviae Miltiorrhizae Radix et Rhizoma, the order of bioaccessibility was: danshensu (50.19%) > salvianolic acid B (33.44%) > lithospermic acid (27.34%) > salvianolic acid A (21.71%) > rosmarinic acid (12.31%). In the simulated intestinal fluid digestion extract of Salviae Miltiorrhizae Radix et Rhizoma, the order of bioaccessibility was: 15,16-dihydrotanshinone Ⅰ (5.45%) > tanshinone Ⅰ (3.67%) > cryptotanshinone (3.29%) > tanshinone ⅡA (3.01%) > salvianolic acid A (2.39%) > lithospermic acid (1.57%) > salvianolic acid B (1.02%) > danshensu (0.41%) > rosmarinic acid (0.34%). In conclusion, the UHPLC method established in this study can be applied for accurately and sensitively detecting the contents of 6 salvianolic acids and 4 tanshinones in Salviae Miltiorrhizae Radix et Rhizoma. The results of semi-biomimetic extraction showed that not all components were extracted with simulated gastric fluid and simulated intestinal fluid, especially rosmarinic acid and salvianolic acid B. Therefore, in the quality study of Salviae Miltiorrhizae Radix et Rhizoma and its extract, bioavailability should be considered at the same time when select quality markers and determine their content limits.

Chemokine receptor CX3CR1 promotes local remodeling of monocyte-derived Langerhans cell subsets to maintain chronic skin inflammation / 中华微生物学和免疫学杂志

Objective:To investigate the role of chemokine receptor CX3CR1 in chronic skin inflammation and its regulatory mechanism.Methods:Wild type (WT) C57BL/6 mice and Cx3 cr1 GFP/GFP mice were induced by DNFB to establish acute and chronic allergic contact dermatitis (ACD) model. Ear inflammation and swelling were observed with hematoxylin-eosin (HE) staining. Flow cytometry (FCM) was used to detect the changes in classical Langerhans cell (LC) and monocyte-derived LC (Mo-LC), as well as the expression of major histocompatibility complex Ⅱ (MHCⅡ), inducible nitric oxide synthase (iNOS) and TNF-α. Changes in epidermal LC in UV irradiation-induced dermatitis models were also analyzed. In human chronic skin inflammation, CX3CL1 expression was detected using immunohistochemistry, RT-PCR and Western blot and CD1a, CD14 and CD207 expression was observed with immunofluorescence staining. Results:In the chronic ACD model, Cx3 cr1 GFP/GFP mice showed significantly alleviated ear inflammatory and swelling as compared with WT mice, but no significant difference was found in the acute ACD model. The percentages of Mo-LC were decreased in the chronic ACD model and after three weeks of UV irradiation. Moreover, MHCⅡ, TNF-α and iNOS expressed by Mo-LC were significantly upregulated as compared with those by classical LC. CX3CL1 expression was significantly upregulated and the numbers of CD14 + monocytes and CD1a + langerin - Mo-LC were dramatically increased in human chronic skin inflammation. Conclusions:CX3CR1 might maintain inflammatory response by regulating local remodeling of Mo-LC in chronic skin inflammation.

Study on ergonomic intervention to relieve work-related musculoskeletal disorders among assembly workers in a railway vehicle manufacturing enterprise / 环境与职业医学

Background Work-related musculoskeletal diseases (WMSDs) occur in a variety of occupational populations. Because of their various discomfort and serious disease burden, they have become an important issue worthy of attention in the field of occupational health. The prevention and control of WMSDs is one of the public health problems to be solved. Objective To evaluate the intervention effect on WMSDs among assembly workers in a railway vehicle manufacturing enterprise, so as to provide scientific basis for the prevention and control of WMSDs. Methods A total of 250 assembly workers in a railway vehicle manufacturing enterprise were selected using convenience sampling from August to December 2017. The Chinese Musculoskeletal Questionnaire was used for epidemiological investigation, and the Ergonomic Checkpoints was used for ergonomic inspection and worker interview. According to the above survey results, a six-month intervention plan including stepladder improvement and ergonomics training were implemented in the assembly workshop from September 2018 to February 2019. The intervention effects including the awareness of WMSDs, the exposure level of ergonomic load, and the occurrence of WMSDs symptoms were evaluated with relevant cross-sectional survey results before and after the intervention. The scores of WMSDs symptom intensity, symptom duration, and symptom frequency from low to high were 0-10, 1-4, and 1-5, respectively. Results After the intervention, the awareness rates of assembly workers on WMSDs types, affected body sites, influencing factors, preventive measures, and symptoms all increased from 52.3%, 51.9%, 25.5%, 19.1%, and 51.5% to 68.5%, 61.3%, 48.1%, 40.9%, and 61.3%, respectively (P<0.05). After the intervention, the proportion of assembly workers who "often" bend their head backwards frequently decreased from 34.6% to 21.8%, the proportion who "often" keep their trunk backward for a long time decreased from 26.6% to 15.0%, and the proportion who "never" raise their arms frequently increased from 3.4% to 9.0% (P<0.05). After the intervention, the scores of WMSDs symptom intensity in neck, shoulders, upper back, low back, elbows, hands/wrists, hips/thighs, knees, and ankles/feet all decreased, and the medians were mostly decreased from 6 to 3 (P<0.05); the scores of WMSDs symptom duration only decreased in neck (P<0.05) and there was no significant difference in the other body sites before and after the intervention; the median scores of WMSDs symptom frequency in low back, hands/wrists, and hips/thighs decreased from 3 to 2 (P<0.05). Conclusion The six-month intervention of stepladder improvement and ergonomics training among assembly workers in a railway vehicle manufacturing enterprise can improve workers' awareness of WMSDs, and reduce the exposure frequency of awkward postures and the intensity, duration, and frequency of WMSDs symptoms.

Influencing factors for work-related musculoskeletal disorders among assembly workers in four manufacturing enterprises / 环境与职业医学

Background The prevalence rate of work-related musculoskeletal disorders (WMSDs) among manufacturing workers is relatively high and has been widely concerned. However, research on the prevalence and risk factors of multi-site WMSDs is still insufficient. Objective To explore the prevalence and risk factors of multi-site WMSDs of assembly workers in four manufacturing enterprises. Methods The "Chinese Musculoskeletal Questionnaire" was used to conduct a cross-sectional survey among 1401 assembly workers selected by convenient sampling in four manufacturing enterprises, and their demographic characteristics, the prevalence of WMSDs in various body parts, and the information about biomechanical factors, work organizations, work environment, and psychosocial factor exposure were collected. The prevalence of WMSDs and multi-site WMSDs were estimated, Pearson χ2 test was used for univariate analysis of multi-site WMSDs risk factors, and logistic regression was used for multi-factor analysis. Results The total prevalence rate of WMSDs was 54.9% (769/1 401). The top three affected sites were neck (41.4%), shoulders (30.7%), and wrist/hand (25.1%). The prevalence rate of multi-site WMSDs was 41.9% (587/1 401). The prevalence rates of multi-site WMSDs in railway vehicle assembly and riveting workers were higher than those in electronic parts processing and glass manufacturing workers (P<0.001). The results of logistic regression analysis showed that individual factors such as female (OR=2.09, 95%CI: 1.48−2.97) and drinking (OR=1.52, 95%CI: 1.05−2.18), biomechanics factors such as keeping head down for a long time (OR=1.37, 95%CI: 1.22–1.53), keeping bending frequently (OR=1.18, 95%CI: 1.03–1.34), and keeping arms up for a long time (OR=1.25, 95%CI: 1.10–1.41), work organizational factors such as electronic parts processing, railway vehicle assembly, and riveting (OR values were 3.23, 5.70, and 13.83, respectively), environmental factors such as temperature a little cold (OR=4.84, 95%CI: 1.90–12.37), noise seriously affecting work (OR=2.25, 95%CI: 1.23–4.11), and psychosocial factors such as high job demands (OR=1.47, 95%CI: 1.04–2.08), fatigue after work (OR=1.92−2.61) were risk factors of multi-site WMSDs. Conclusion The prevalence rate of multi-site WMSDs in assembly workers is high, and the main influencing factors include individual factors, awkward work postures, environmental factors, and psychosocial factors.

The value of event-related potential P300 for diagnosing cognitive impairment after stroke / 中华物理医学与康复杂志

Objective:To observe the utility of event-related potential P300 in diagnosing post-stroke cognitive impairment.Methods:Forty-nine stroke survivors at high risk of cognitive impairment formed the observation group, while 54 healthy volunteers were the control group. General clinical data and Montreal Cognitive Assessment Scale (MoCA) scores were compiled for all of the subjects, and the two groups′ P300 latencies, amplitudes and mean reaction times (MRTs) were compared. A total MoCA score <26 (corrected for education level) was taken as the diagnostic criterion for cognitive impairment. The receiver operating characteristics (ROC) curve was employed to analyze the diagnostic efficacy of P300 for post-stroke cognitive impairment and determine the diagnostic cutoff.Results:(1) The average MoCA score, P300 latency and P300 MRT of the observation group were all significantly different from the control group′s averages. There was, however, no significant difference between the two groups′ median P300 amplitudes. (2) According to the ROC curve analysis, the diagnostic limit of P300 latency was 376.50ms. With the area under the curve 0.795, sensitivity was 70.8% and specificity was 78.9%. The diagnosis cut-off value of P300 MRT was 423.35ms, with the area under the curve 0.695, giving a sensitivity of 80.0% and a specificity of 52.6%.Conclusions:Event-related potential P300 has useful efficacy in diagnosing post-stroke cognitive impairment.

Bioinformatics Analysis on Key Genes and Immune Infiltration of Osteosarcoma / 中国医学科学院学报

Objective To screen the potential key genes of osteosarcoma by bioinformatics methods and analyze their immune infiltration patterns. Methods The gene expression profiles GSE16088 and GSE12865 associated with osteosarcoma were obtained from the Gene Expression Omnibus(GEO),and the differentially expressed genes(DEGs)related to osteosarcoma were screened by bioinformatics tools.Gene Ontology(GO)annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and analysis of immune cell infiltration were then carried out for the DEGs.The potential Hub genes of osteosarcoma were identified by protein-protein interaction network,and the expression of Hub genes in osteosarcoma and normal tissue samples was verified via the Cancer Genome Atlas(TCGA). Results A total of 108 DEGs were screened out.GO annotation and KEGG pathway enrichment revealed that the DEGs were mainly involved in integrin binding,extracellular matrix (ECM) structural components,ECM receptor interactions,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Macrophages were the predominant infiltrating immune cells in osteosarcoma.Secreted phosphoprotein 1(SPP1),matrix metallopeptidase 2(MMP2),lysyl oxidase(LOX),collagen type V alpha(II)chain(COL5A2),and melanoma cell adhesion molecule(MCAM)presented differential expression between osteosarcoma and normal tissue samples(all P<0.05). Conclusions SPP1,MMP2,LOX,COL5A2,and MCAM are all up-regulated in osteosarcoma,which may serve as potential biomarkers of osteosarcoma.Macrophages are the key infiltrating immune cells in osteosarcoma,which may provide new perspectives for the treatment of osteosarcoma.

Effect of Shanhaidan Granules combined with tadalafil on erectile dysfunction: A multi-center clinical trial / 中华男科学杂志

Objective@#To observe the clinical effect and safety of Shanhaidan Granules (SHDG) combined with tadalafil tablets (TT) in the treatment of ED.@*METHODS@#In this open multi-center case-control clinical trial, we enrolled 247 ED patients according to the designed criteria, and treated them orally with SHDG at 10 g per time tid (n = 74), TT at 5 mg per time bid (n = 52), or SHDG + TT at the above doses (n = 121), all for 8 weeks. Before and after medication, we recorded the IIEF-6, erection hardness scores (EHS), traditional Chinese medicine syndromes (TCMS) scores, penile cavernous blood flow parameters and adverse reactions, and compared them between the 3 groups of patients.@*RESULTS@#After 8 weeks of treatment, all the patients showed significantly increased IIEF-6, EHS and TCMS scores in comparison with the baseline (P < 0.05). The total effectiveness rates in the SHDG, TT and SHDG + TT groups were 60.8%, 67.3% and 69.4% respectively based on the IIEF-6 scores, remarkably higher in the TT and SHDG + TT groups than in the SHDG group (P < 0.05), and 40.5%, 32.7% and 63.6% respectively according to the TCMS scores, markedly higher in the SHDG and SHDG + TT groups than in the TT group (P < 0.05). Single-center data manifested significantly increased peak systolic velocity (PSV) of the penile artery in the SHDG + TT and TT groups (P < 0.05). The improvement values of relevant parameters were remarkably higher in the SHDG + TT group than in the TT and SHDG groups, so were IIEF-6 scores in the TT than in the SHDG group, and TCM syndromes in the SHDG than in the TT group. No medication-related adverse events were found in any of patients after treatment, except for some mild side effects including muscle soreness and gastrointestinal reactions in a few cases, all soon relieved, none with abnormalities in blood and urine routine tests or hepatic and renal function indicators.@*CONCLUSIONS@#Shanhaidan Granules combined with tadalafil can significantly improve the erectile function and reduce TCM syndromes in ED patients, and therefore can be applied effectively and safely in clinical practice./.