Meta-analysis of clinical prognosis of stage Ⅰ breast reconstruction after modified radical mastectomy / 中国医师进修杂志

Objective:To evaluate the clinical prognosis of stage Ⅰ breast reconstruction after modified radical mastectomy by using Meta-analysis.Methods:Wanfang Resource Database, Chinese Journal Full-Text Database, VIP Information Resource System, Chinese Scientific and Technological Journal Database, Cochrane Library, EMbase, PubMed were searched by computer. The retrieval time was from the establishment of each database to August 25, 2021. To collect clinical control test group (CCT) and randomized controlled trial(RCT) on breast reconstruction after radical mastectomy. The researchers independently searched the inclusion and exclusion criteria, screened and sorted them, evaluated them, extracted relevant data, and performed Meta-analysis with Rev man 5.3 software.Results:Twelve research were enrolled in this study.the Meta-analysis results showed that there were no significant differences in the local recurrence rate, distant metastasis rate, 3-year tumor free survival rate and complications between the patients performed stage Ⅰ breast reconstruction after modified radical mastectomy and the patients only performed modified radical mastectomy ( OR = 0.91, 95% CI 0.50 - 1.68, P = 0.77; OR = 0.66, 95% CI 0.42 - 1.06, P = 0.09; OR = 1.22, 95% CI 0.77 - 1.93, P = 0.40; OR = 0.91, 95% CI 0.58 - 1.41, P = 0.66). The quality of life score in the patients performed stage Ⅰ breast reconstruction after modified radical mastectomy was higher than that in the patients only performed modified radical mastectomy ( MD = 9.79, 95% CI 8.82 - 10.76, P<0.001). Conclusions:StageⅠbreast reconstruction after modified radical mastectomy can reduce the pressure of patients due to physical defects, help patients build up confidence and improve their quality of life.

Occupational health literacy level and its influencing factors among key populations in China in 2022 / 中国职业医学

Objective To analyze the level of occupational health literacy (OHL) and its influencing factors among key populations in China. Methods The front-line workers from 31 provinces, autonomous regions, municipalities, and Xinjiang Production and Construction Corps in China were selected as the research subjects using a combination of stratified cluster random sampling and probability proportional sampling. The Occupational Health Literacy Questionnaire of National Key Populations was used to investigate the OHL level. Results In 2022, a total of 340 506 people from 23 industries were surveyed. Among them, 168 455 and 172 051 people were surveyed in the secondary and tertiary industries, respectively. The OHL level of the research subjects was 52.6%. The OHL levels of workers in the secondary and tertiary industries were 56.5% and 48.9%, respectively. The results of multivariate logistic regression analysis showed that gender, age, marital status, educational level, household registration, monthly income, employment nature, years of service and industry category were independent influencing factors for OHL level of the research subjects (all P<0.01). Specifically, females had a higher OHL level than males (P<0.01); the older the age, the higher the education level, the higher the monthly income level, the higher the OHL level (all P<0.01); the level of OHL in unmarried people was higher than that in married people (P<0.01); the OHL level of workers with non-agricultural household registration was higher than that of workers with agricultural household registration (P<0.01); the OHL levels of workers in state-owned enterprises, foreign-funded enterprises and public institutions were higher than those in private enterprises (all P<0.01); the level of OHL in the group with 21.0-43.0 years of service was lower than that in the other years of service groups (all P<0.01); the OHL level of workers in the secondary industry was higher than that in the tertiary industry (P<0.01). Conclusion The workers in the key industries selected by the tertiary industry, the private enterprises in the secondary industry, those with more than 21.0 years of service, and the disadvantaged groups with younger age low income, low education level, and the agricultural household registration are the key groups for the improvement of OHL level in the future. Appropriate intervention methods and strategies should be actively explored to improve the OHL of these key populations.

Design and synthesis of peptide-drug conjugates and fluorescent probe based on α-conotoxin ArIBV11L,V16D / 药学学报

italic>α-Conotoxin ArIB[V11L,V16D] is currently the most optimal selective inhibitor of α7 nicotinic acetylcholine receptor (nAChR) known. In order to explore chemical modification methods and enrich its application in targeting nAChR, this study utilized the linker to covalently connect camptothecin and 7-amino-4-methylcoumarin to the [2,4] disulfide bond of ArIB[V11L,V16D]. Therefore, two peptide-drug conjugates (PDCs), ArIB[V11L,V16D]-5 and ArIB[V11L,V16D]-6, and one fluorescent-labeled peptide, ArIB[V11L,V16D]-7 were constructed. Cytotoxicity evaluation showed that the IC50 values against non-small cell lung cancer cell line A549 of the two PDCs were respectively 1.3 and 4.1 times of camptothecin, indicating slight reduction in activity at the cellular level which was related to the linker structure. Fluorescence spectrum scanning revealed that the excitation and emission wavelength of the fluorescent-labeled peptide were 340 nm and 403 nm respectively, and the fluorescence features of 7-amino-4-methylcoumarin as a marker were retained without fluorescence quenching. This modification strategy laid a solid foundation for the further application of α-conotoxin ArIB[V11L,V16D] in PDCs and fluorescent probes.

Simulation analysis on the distribution characteristics and movement rules of particulate matter in a convenience store / 中国职业医学

Objective: The spatial distribution model of particulate matter based on time change in a specific place was established to analyze the spatial and temporal distribution characteristics and movement of particulate matter. Methods: A convenience store was selected as the research subject. The micro-climate and particle number concentration (PNC) of the site were detected, and numerical simulation was carried out by computational fluid dynamics (CFD) simulation method. Based on the discrete phase model, the temporal and spatial distribution characteristics and movement rules of simulated particles were analyzed. Results: The wind speed at the entrance of the convenience store was low and almost unchanged during the detection, while the wind speeds outside and inside outlets were high and changed sharply. The PNC of particle size of 0.02-1.00 μm was higher than that of particle size >1.00 μm (all P<0.05). The PNC with particle size of 0.02-1.00 μm from high to low were checkout counter, entrance, outer outlet and inner outlet (all P<0.05). The PNC of the checkout counter and entrance varies greatly, while the PNC of the outer outlet and inner outlet was relatively steady. The CFD simulation results showed that particles exhaled by individuals near the entrance of the checkout counter of the convenience store could be expelled outdoors more quickly with the influence of airflow. However, particles exhaled by individuals in the middle of the shelves remained suspended indoors for a longer period of time compared to those near the checkout counter. Particles emitted from the air conditioning outlet diffuse throughout the entire store and reach a steady state in 300 seconds. Conclusion: The particulate matter in the convenience store was mainly small particle with the size less than 1.00 μm. The residence time, downward trend and number of suspended particulates of human exhaled particles were related to air flow. The particulates escaped from the air conditioner could quickly spread to almost the entire convenience store.

Introduction of the national technical plan for monitoring occupational health literacy of key population groups in 2022 / 中国职业医学

Occupational health literacy refers to the awareness and ability of workers to obtain basic knowledge of occupational health, practice healthy working styles and lifestyles, prevent the risk of occupational and work-related diseases, and maintain and promote their own health. In 2022, for the first time, China carried out nationwide monitoring for occupational health literacy of key populations. The National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention was responsible for technical support, formulating the National Technical Plan for Occupational Health Literacy Monitoring and Intervention of Key Populations, and formulating relevant requirements and specifications for monitoring purposes, monitoring scope and objects, sampling methods, monitoring content and methods, organization and implementation of field investigation, and quality control. In addition, the National Occupational Health Literacy Monitoring Questionnaire for Key Groups was provided, and the monitoring and intervention of occupational health literacy for key groups in the second- and third-key industries has been organized nationwide, so as to understand the occupational health literacy of the occupational population in China and provide important support for promotion of high-quality construction of healthy China.

Osteosarcoma with bone metastasis or pulmonary metastasis show distinct genomic manifestations / 中华骨科杂志

Objective:To investigate the genomic manifestation and pathogenesis of osteosarcoma with different relapse pattens, which were respectively initially presented with bone metastasis or pulmonary metastasis.Methods:From May 1, 2021 to October 1, 2021, 38 fresh tumor specimens and some paraffin-embedded specimens of high-grade osteosarcoma were collected in Peking University People's Hospital, including 29 males and 9 females, aged 19.6±2.2 years (range, 6-61 years). Among the 38 cases, 12 cases had initial bone metastasis (group A) and 26 cases had initial lung metastasis (group B), of which 15 cases (40%, 15/38) had paired specimens of primary and metastatic lesions. Based on Illumina NovaSeq 6000, we analyzed whole-exome sequencing (WES) as well as transcriptome for osteosarcoma with paired samples in different relapse patterns. During all their treatment courses, we also collected their paired samples to reveal these tumors' evolution. We sought to redefine disease subclassifications for osteosarcoma based on genetic alterations and correlate these genetic profiles with clinical treatment courses to elucidate potential evolving cladograms.Results:We found that osteosarcoma in group A mainly carried single-nucleotide variations (83%, 10/12), displaying higher tumor mutation burden [4.9 (2.8, 12.0) & 2.4 (1.4, 4.5), P=0.010] and neoantigen load [743.0 (316.5, 1,034.5) & 128.5 (49.0, 200.5), P=0.003], while those in group B mainly exhibit structural variants (58%, 15/26). The mutation spectrum showed that there was a significant difference in age-related gene imprinting 1 between the bone metastasis group and the lung metastasis group ( P=0.005). Samples were randomly selected from group A (3 patients) to investigate immunologic landscape by multiplex immunohistochemistry, from which we noticed tertiary lymphatic structure from one patient from group A. High conservation of reported genetic sequencing over time was found in their evolving cladograms. Conclusion:Osteosarcoma with mainly single-nucleotide variations other than structural variants might exhibit biological behavior predisposing toward bone metastases with older in age as well as better immunogenicity in tumor microenvironment.

A meta-analysis of progressive pulmonary micro nodules in osteosarcoma / 中华骨科杂志

Objective:To identify the prevalence of pulmonary micro nodule (PMN) in osteosarcoma, investigate radiologic features of progressive PMN, and provide evidence for early diagnosis of pulmonary metastasis of osteosarcoma.Methods:Electronic articles published in PubMed, EMBASE, Web of Science and the Cochrane Library databases between January 1, 2000, and September 1, 2022, were searched and critically evaluated. The authors independently reviewed the abstracts and extracted data on the prevalence of PMN in osteosarcoma and radiologic features of progressive PMN. Seven high quality studies were finally included in the meta-analysis with evidence level III.Results:The pooled prevalence of PMN in osteosarcoma was 36.0%, 95% CI (14.6%, 57.3%). The pooled progressive rate of PMN was 52.5%, 95% CI (37.7%, 67.2%). As for a specific PMN, it was more likely to progress which had a larger Dmax, HR=2.40, 95% CI (1.06, 5.42), P=0.035. No significant difference was found in number, component, and border. Conclusion:PMN is quite common in patients with osteosarcoma. About half of the patients suffered the progression of PMN, and it is related to several risk factors.

Diagnostic Value and Safety of Electromagnetic Navigation Bronchoscopy in Peripheral Pulmonary Lesions: A Meta-analysis / 中国肺癌杂志

BACKGROUND@#The incidence and mortality of lung cancer have always been at the forefront of malignant tumors. With the development of lung cancer detection techniques, more peripheral pulmonary lesions (PPLs) have been detected. The diagnostic accuracy of procedures for PPLs keeps controversial. This study aims to systematically evaluate the diagnostic value and the safety of electromagnetic navigation bronchoscopy (ENB) in the diagnosis of PPLs.@*METHODS@#The relevant literatures in the diagnostic yield of PPLs by ENB were systematically retrieved from Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure, Embase, PubMed, Cochrane Library and Web of Science. The software of Stata 16.0, RevMan 5.4 and Meta-disc 1.4 were used to conduct the meta-analysis.@*RESULTS@#A total of 54 literatures with 55 studies were included in our meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of ENB in the diagnosis of PPLs were 0.77 (95%CI: 0.73-0.81), 0.97 (95%CI: 0.93-0.99), 24.27 (95%CI: 10.21-57.67), 0.23 (95%CI: 0.19-0.28) and 104.19 (95%CI: 41.85-259.37), respectively. The area under curve (AUC) was 0.90 (95%CI: 0.87-0.92). Meta-regression and subgroup analyses indicated that the potential heterogeneity resulted from study type, additional localization techniques, sample size, lesion size and type of sedation. The use of additional localization techniques and general anesthesia have improved the diagnostic efficiency of ENB in PPLs. The incidence of adverse reactions and complications associated with ENB was very low.@*CONCLUSIONS@#ENB provides well diagnostic accuracy and safety.

The In Vivo Intervention and Relative Mechanism of Genistein on the Inflammation and Thrombophilia in Lymphoma-Bearing Mice / 中国实验血液学杂志

OBJECTIVE@#To investigate the in vivo intervention and relative mechanism of Genistein (GEN) on tumor-associated inflammatory and tumor thrombophilia in lymphoma-bearing mice.@*METHODS@#Forty female Balb/c mice aged 5-6 weeks were injected with murine-derived Pro B-cell lymphoma cell line 38B9 to establish a lymphoma mouse model, which was randomly divided into control group, tumor-bearing group, GEN drug intervention group and cyclophosphamide (CTX）drug intervention group. Histopathologic was used to evaluate the tumorigenesis. Tumor formation was observed, and tumor tissues were collected of HE and immunohistochemical staining. ELISA and flow cytometry were used to detect the expression of inflammatory factors and the changes of thrombus indices in plasma after intervention of GEN and Cyclophosphamide (CTX) respectively. Immunohistochemistry method was used to detect the expression of CD19 in tomor tissues of tummor bearing mice.@*RESULTS@#After 14 days of tumor bearing, the mice were tumorigenic. The lymphoma cells were diffusely distributed in the tumor tissue and the expression of CD19 in the tumor tissue was positive. The inflammatory factors such as IL-6, NETs and CLEC-2, and thrombotic indices such as TF, FIB and D-D in lymphoma-bearing mice were significantly higher than those before tumor-injection and lower than those after drug-intervention (all P<0.05). The levels of CLEC-2 and D-D in GEN group were significantly lower than those in CTX group (P<0.05).@*CONCLUSION@#Tumor-associated inflammation and thrombophilia exist in lymphoma-bearing mice. GEN shows better anti-inflammatory and anti-thrombotic effects compared with CTX by interfering with tumor inflammatory factors.

Projected burden of stroke in China through 2050 / 中华医学杂志(英文版)

BACKGROUND@#Stroke is the leading cause of death in China, and predicting the stroke burden could provide essential information guiding the setting of medium- and long-term health policies and priorities. The study aimed to project trends associated with stroke burden in China through 2050, not only in terms of incidence and mortality but also for prevalence and disability-adjusted life years (DALYs).@*METHODS@#Data on stroke rates in incidence, prevalence, deaths, and DALYs in China between 1990 and 2019 were obtained from a recent Global Burden of Disease study. Demographic-specific trends in rates over time were estimated using three models: the loglinear model, the Lee-Carter model, and a functional time series model. The mean absolute percentage error and the root mean squared error were used for model selection. Projections up to 2050 were estimated using the best fitting model. United Nations population data were used to project the absolute numbers through 2050.@*RESULTS@#From 2019 to 2050, the crude rates for all measures of the stroke burden are projected to increase continuously among both men and women. We project that compared with those in 2019, the incidence, prevalence, deaths, and DALYs because of stroke in China in 2050 will increase by 55.58%, 119.16%, 72.15%, and 20.04%, respectively; the corresponding increases in number were 2.19, 34.27, 1.58, and 9.21 million. The age-standardized rate is projected to substantially decline for incidence (8.94%), death (40.37%), and DALYs (43.47%), but the age-standardized prevalence rate is predicted to increase by 10.82%. By 2050, the burden of stroke among the population aged ≥65 years will increase significantly: by 104.70% for incidence, by 218.48% for prevalence, by 100.00% for death, and by 58.93% for DALYs.@*CONCLUSIONS@#With the aging population in China increasing over the next three decades, the burden of stroke will be markedly increased. Continuous efforts are needed to improve stroke health care and secondary prevention, especially for older adults.

Association between wrist pain and awkward postures among workers in 10 key industries / 环境与职业医学

Background Prolonged awkward postures during occupational activities can lead to excessive musculoskeletal load on the wrist of workers and symptoms such as wrist pain or discomfort. Objective To survey the prevalence of wrist pain among workers in 10 key industries and analyze its correlation with wrist working postures. Methods By using stratified cluster sampling method, workers from 10 key industries, such as footwear manufacturing industry, shipbuilding manufacturing industry, and automobile manufacturing industry, were selected from seven regions in North China, East China, Central China, South China, Southwest China, Northwest China, and Northeast China. The demographic information, wrist working postures, pain in wrist of the workers were collected through a cross-sectional survey. Pearson χ2 test was used to compare prevalence by selected factors, trend χ2 test for between group comparison, and unconditional logistic regression models for the association of wrist working postures with wrist pain. Results There were 64052 workers enrolled in this survey, and 56286 provided valid questionnaires (the effective rate was 87.8%). According to the survey, the prevalence of wrist pain was 23.3% (13112/56286), and the industries with higher prevalences were footwear manufacturing (27.1%, 1927/7106), automobile manufacturing (24.9%, 5378/21560), and shipbuilding and related equipment manufacturing (24.4%, 850/3488) industries. Finger pinching (OR=2.09, 95%CI: 1.95-2.24), frequent wrist bending (OR=2.03, 95%CI: 1.92-2.15), fixed wrist bending (OR=1.77, 95%CI: 1.69-1.85), wrist on hard edge (OR=1.34, 95%CI: 1.28-1.40), and arms over shoulders (OR=1.11, 95%CI: 1.05-1.17) increased the risk of reporting wrist pain. Conclusion Awkward postures are related to wrist pain among workers in selected 10 key industries. The related factors are wrist on hard edge, frequent wrist bending, finger pinching, fixed wrist bending, and arms over shoulders.

Clinical features of fundus lesions of 74 patients with acquired immunodeficiency syndrome in Shenyang / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical features and factors of fundus lesions in patients with acquired immunodeficiency syndrome(AIDS)in Shenyang and the relationship between fundus lesions and CD4+T cell count.METHODS: Retrospective case study. A total of 74 cases with AIDS who were treated in the Central Hospital of Liaoning Electric Power Supply Co., Ltd., from January 2021 to December 2021 were selected. The fundus manifestation and CD4+T cell count of the patients were analyzed.RESULTS: The total detection rate of fundus lesions in AIDS patients was 58%. CD4+T cell count in the patients with fundus lesions was significantly lower than that in the patients with normal fundus [29(6, 55)/μL vs. 76(35, 103)/μL, P<0.01]. The rate of fundus lesions was the highest in the patients with CD4+T cell count ≤ 50/μL(74%). Logistic regression analysis showed that as the CD4+T cell count increased, the incidence of fundus lesions decreased(OR=0.977, 95%CI 0.964～0.991, P<0.01).CONCLUSION: Fundus lesions in AIDS patients related to CD4+T cell count. Decreasing CD4+T cell count was a risk factor of fundus lesions for AIDS patients. Routine fundus examination is important for the early diagnosis of fundus lesions in AIDS patients.

The mechanism of "Trichosanthis Fructus-Allii Macrostemonis Bulbus" on phlegm and blood stasis syndrome-related cardiovascular diseases based on network pharmacology and experimental verification / 药学学报

This study aimed to investigate the mechanism of "Trichosanthis Fructus-Allii Macrostemonis Bulbus" (GX) on phlegm and blood stasis syndrome (PBSS) rats combining the methods of network pharmacology and experimental verification. Animal experiment ethical requirements were approved by the Ethical Committee Experimental Animal Center of Anhui University of Chinese Medicine (grant number: AHUCM-rats-2021070). Based on the HPLC-Q-TOF-MS analysis and database, 69 chemical constituents of GX and 163 targets of GX for the treatment of phlegm and blood stasis-related cardiovascular diseases were obtained. Then, key targets such as serine/threonine kinase 1 (Akt1), tumor necrosis factor (TNF), interleukin 6 (IL6), vascular endothelial growth factor A (VEGFA), cellular tumor antigen p53 (Tp53) were screened. Pathway analysis showed that the targets of GX in the treatment of phlegm and blood stasis-relate cardiovascular diseases were mainly involved in PI3K/Akt signaling pathway, sphingolipid metabolism, platelet activation, hypoxia inducible factor-1 (HIF-1), ras-proximate-1 (rap1) and other signaling pathways. In addition, molecular docking analysis showed that apigenin, cucurbitacin D, linolenic acid and kaempferol and other key components had potential binding ability with Akt1, TNF, IL6, VEGFA and Tp53. In the animal experiments, compared to the phlegm and blood stasis syndrome group, GX could significantly improve the traditional Chinese medicine syndrome score, blood lipid, vascular endothelial structure disorders and reduce serum endothelin-1 (ET-1) level, increase serum nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) levels, which could restore aortic endothelial function. In addition, the expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in aorta could be significantly reduced, which could improve the vascular endothelial injury of aorta. Western blot revealed that GX could significantly decrease the phosphorylation levels of phosphoinositide 3-kinase (PI3K) and Akt in aorta. This study revealed the mechanism of GX in treatment of phlegm and blood stasis-relate cardiovascular diseases is consistent with the characteristics of multiple ingredients, multiple targets and multiple pathways. In addition, this study also clarified that the reversal of pathological of phlegm and blood stasis syndrome rats may be related to GX inhibiting PI3K/Akt signaling pathway, which could improve vascular inflammation and vascular endothelial function injury.

Volatile Oil of Linderae Radix Induces Apoptosis and Autophagy of Gastric Cancer AGS Cells via AMPK/mTOR Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effects of the volatile oil of Linderae Radix on the apoptosis and autophagy of human gastric cancer cell line AGS， and to explore the regulatory role of adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway in this process. MethodThe volatile oil of Linderae Radix was extracted by steam distillation， and the effect of the volatile oil on the viability of AGS cells was detected by thiazolyl tetrazolium （MTT） colorimetry. The optimal intervention dose and time were determined according to the half maximal inhibitory concentration （IC50） for subsequent research. The blank， low， medium， and high-dose volatile oil （0， 15， 30， 60 mg·L-1） groups and the positive drug cyclophosphamide （CTX， 350 mg·L-1） group were designed. AGS cells were treated with different doses of volatile oil for 48 h. The changes in cell proliferation， cycle， and migration were measured by colony formation assay， flow cytometry， and cell scratch test， respectively. Hematoxylin-eosin （HE） staining was employed to observe the changes of cell morphology， Annexin-V/propidium iodide （PI） double staining to measure the apoptosis， and acridine orange （AO） staining to measure the autophagy level of the cells. Western blotting was employed to determine the expression of the autophagy effectors Beclin-1， p62， microtubule-associated protein 1-light chain 3 （LC3）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved Caspase-3， cleaved poly ADP-ribose polymerase （PARP）， adenosine monophosphate-activated protein kinase （AMPK）， phosphorylated AMPK （p-AMPK）， mTOR， and phosphorylated mTOR （p-mTOR）. ResultCompared with the blank group， 24 h and 48 h of intervention with the volatile oil of Linderae Radix inhibited the viability of AGS cells in a concentration- and time-dependent manner （P<0.05， P<0.01）. Compared with the blank group， the volatile oil decreased the cell proliferation and migration （P<0.05， P<0.01） and blocked the AGS cell cycle in G2/M phase （P<0.05， P<0.01） in a concentration-dependent manner. The cells treated with the volatile oil became spherical and smaller， with the formation of apoptotic bodies and increased apoptosis rate （P<0.05， P<0.01）. As the dose of the volatile oil increased， the number of autophagosomes increased and the red fluorescence gradually enhanced， indicating the elevated level of autophagy. Compared with the blank group， different doses of volatile oil up-regulated the protein levels of Beclin-1， LC3 Ⅱ/LC3 Ⅰ， cleaved Caspase-3， cleaved PARP， Bax/Bcl-2， and AMPK （P<0.05， P<0.01） and down-regulated the protein levels of p62 and p-mTOR （P<0.05， P<0.01）. ConclusionThe volatile oil of Linderae Radix induces the apoptosis and exerts the autophagy-mediated growth inhibition of AGS cells by regulating the AMPK/mTOR signaling pathway.

Research progress of exosome drug loading system / 中国药房

Exosome is a kind of vesicle secreted by a variety of cells with lipid bilayer membrane structure， which has good biocompatibility， high targeting and high stability， and is a natural nanoscale drug carrier with great development potential in drug delivery system. In this paper， exosomes and their properties， exosome drug delivery pathways and methods， the design strategy of engineered exosome drug delivery systems for targeted disease therapy， and the application of exosome drug delivery systems in the treatment of a variety of diseases were reviewed. Exosome drug delivery pathways could be divided into two categories： exogenous and endogenous. Common exosome drug delivery methods included electroporation， co-incubation， and ultrasound. Engineered exosome drug delivery system can further improve drug loading and enhance drug targeting. The main way of engineering is to modify exosome surface through genetic engineering technology， physical modification， chemical modification， etc. Exosome drug delivery system provides a new idea for targeted therapy of arthritis， tumor， brain and other diseases.

Anti-inflammatory Effect and Mechanism of Duhuo Jishengtang on Rheumatoid Arthritis Rats Based on TLR2/p38 MAPK/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the anti-inflammatory effect of Duhuo Jishengtang （DHJST） on collagen-induced arthritis （CIA） model rats and its effect on the Toll-like receptor 2 （TLR2）/p38 mitogen-activated protein kinase （MAPK）/nuclear factor-κB （NF-κB） signaling pathway. MethodForty-eight male SD rats were randomly divided into the following six groups （n=8）： normal group， model group， methotrexate （MTX） group， low-dose DHJST （DHJST-L） group， medium-dose DHJST （DHJST-M） group， and high-dose DHJST （DHJST-H） group. The CIA model was established by injecting bovine type Ⅱ collagen into the rat tail root with the collagen antibody induction method. After model induction， rats were treated with drugs by gavage. The rats in the MTX group received MTX at 2.0 mg·kg-1， three times a week， and those in the DHJST groups received DHJST at 3.8， 7.6， 15.2 g·kg-1·d-1 for 28 days. The rats in the normal group and the model group were given the same dose of normal saline. The weight of the rats was recorded， and the paw swelling degree was observed. The arthritis index and immune organ index were measured， and the changes in the microcirculation indexes of the rats were detected with a microcirculation detector. Hematoxylin-eosin （HE） staining was used to detect the pathological morphologic changes in rat synovial tissues and the apoptosis rate of synovial cells was detected by flow cytometry to determine the therapeutic effect of DHJST on rheumatoid arthritis. Enzyme-linked immunosorbent assay （ELISA） was used to detect the changes in serum levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， IL-17A， and interferon-γ （IFN-γ）. The protein expression of TLR2， NF-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， p38 MAPK， and p-p38 MAPK was detected by Western blot. ResultCompared with the normal group， the model group showed reduced body weight （P<0.01）， increased paw swelling degree， arthritis index， and immune organ index （P<0.01）， increased comprehensive microvascular score and vascular resistance （P<0.01）， significant hyperplasia of synovial tissues and massive infiltration of inflammatory cells as revealed by pathological sections， and up-regulated expression levels of TNF-α， IL-1β， IL-17A， and IFN-γ in serum， and TLR2， p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in synovial tissues （P<0.01）. Compared with the model group， the DHJST groups showed increased body weight of rats （P<0.01）， decreased paw swelling degree， arthritis index， and immune organ index （P<0.05， P<0.01）， reduced comprehensive microvascular score and vascular resistance （P<0.05， P<0.01）， improved synovial histopathological injury， increased apoptosis rate of synovial cells （P<0.01）， and down-regulated levels of TNF-α， IL-1β， IL-17A， and IFN-γ in serum （P<0.05， P<0.01） and TLR2， p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in synovial tissues （P<0.05， P<0.01）. ConclusionDHJST may alleviate the inflammatory reaction in CIA rats by regulating the TLR2/p38 MAPK/NF-κB signaling pathway， thus exerting its anti-rheumatoid arthritis effect.

The Nucleus Accumbens CRH-CRHR1 System Mediates Early-Life Stress-Induced Sleep Disturbance and Dendritic Atrophy in the Adult Mouse / 神经科学通报·英文版

Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adulthood, one of which is sleep disturbance. As the corticotropin-releasing hormone (CRH)-corticotropin-releasing hormone receptor 1 (CRHR1) system and nucleus accumbens (NAc) play important roles in both stress responses and sleep-wake regulation, in this study we investigated whether the NAc CRH-CRHR1 system mediates early-life stress-induced abnormalities in sleep-wake behavior in adult mice. Using the limited nesting and bedding material paradigm from postnatal days 2 to 9, we found that early-life stress disrupted sleep-wake behaviors during adulthood, including increased wakefulness and decreased non-rapid eye movement (NREM) sleep time during the dark period and increased rapid eye movement (REM) sleep time during the light period. The stress-induced sleep disturbances were accompanied by dendritic atrophy in the NAc and both were largely reversed by daily systemic administration of the CRHR1 antagonist antalarmin during stress exposure. Importantly, Crh overexpression in the NAc reproduced the effects of early-life stress on sleep-wake behavior and NAc morphology, whereas NAc Crhr1 knockdown reversed these effects (including increased wakefulness and reduced NREM sleep in the dark period and NAc dendritic atrophy). Together, our findings demonstrate the negative influence of early-life stress on sleep architecture and the structural plasticity of the NAc, and highlight the critical role of the NAc CRH-CRHR1 system in modulating these negative outcomes evoked by early-life stress.

Role of glutathione transferase in nonalcoholic fatty liver disease: An analysis based on gene expression profile / 临床肝胆病杂志

Objective To investigate the role of glutathione transferase in nonalcoholic fatty liver disease (NAFLD) induced by high-fat diet using the RNA-Seq technique in combination with gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of differentially expressed genes. Methods A total of 14 male C57BL/6J mice were divided into control group with 6 mice and model group with 8 mice by random sampling. The mice in the control group were fed with normal diet, and those in the model group were fed with high-fat diet for 7 consecutive weeks to establish a model of NAFLD. Kits were used to measure the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the level of triglyceride (TG), and HE staining and oil red staining were used to observe liver pathology and deposition of lipid droplets. Liver tissue RNA was extracted for RNA-Seq, and genes with a fold change of ≥2.0 and a P value of 0.05). Compared with the control group, the model group had a significantly higher serum level of TG (2.02±0.50 mmol/L vs 1.00±0.29 mmol/L, t =-4.45, P =0.001). HE staining showed diffuse steatosis and ballooning degeneration in the model group, and oil red staining showed that the model group had a significant increase in orange-red lipid droplets in the cytoplasm of hepatocytes and a significantly higher grade of hepatocyte steatosis than the control group (1.88±0.64 vs 1.00±0.00, t =-3.86, P =0.006). RNA-seq results showed a total of 1367 differentially expressed genes between the two groups, among which there were 608 upregulated genes and 759 downregulated genes, and there were 17 differentially expressed GST genes between the two groups. The top 10 GST genes in terms of fold change were validated, and compared with the control group, the model group had downregulated expression of GSTa2, GSTa3, GSTa4, GSTm1, GSTm2, GSTm3, GSTm4, GSTp1, and GSTo1 and upregulated expression of GSTk1. The results of qRT-PCR were consistent with the results of sequencing. Conclusion GST affects lipid metabolism by participating in various biological processes such as steroid metabolism, fatty acid metabolism, and cholesterol metabolism and is closely associated with the pathogenesis of NAFLD.

Highlights of the EASL clinical practice guidelines on sclerosing cholangitis versus the latest Chinese guideline / 临床肝胆病杂志

In 2022, the European Association for the Study of the Liver issued Clinical practice guidelines on sclerosing cholangitis. With reference to the 2017 edition of Role of endoscopy in primary sclerosing cholangitis: European Society of Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the Liver (EASL) Clinical Guideline (2017) and in comparison to the corresponding contents in Guidelines on the diagnosis and management of primary sclerosing cholangitis (2021) issued by Chinese Society of Hepatology, Chinese Medical Association, in 2021, this article summarizes the updates in diagnosis, treatment, monitoring, and management of special populations and analyzes the basis for updated recommendations and their guiding significance in optimizing the clinical management of primary sclerosing cholangitis (PSC). The comparative analysis shows that the new version of the guidelines is similar to the Chinese guidelines in terms of diagnosis, treatment, and follow-up, and it is worth learning from the technical details such as the recommended dose of ursodeoxycholic acid and long-term follow-up plan. Since PSC is a chronic refractory disease, the drugs recommended by current guidelines cannot delay or reverse disease progression, and there is still a lack of consensus statements on immunotherapy and screening protocols for end-stage complications, which might be the directions for further research.

Disease burden attributable to alcohol consumption in China in1990 and 2019 / 公共卫生与预防医学

Objective To compare and analyze the disease burden caused by drinking in China in 1990 and 2019. Methods The global disease burden database 2019 was used to analyze the attribution score (PAF), mortality, disability adjusted life year (DALY) and other indicators attributed to drinking in China in 1990 and 2019. The disease burden caused by alcohol consumption was compared between China and the world as well as different social demographic index (SDI) regions. Results From 1990 to 2019, the PAF attributed to drinking increased by 12.85%. The number of deaths attributed to drinking increased to 514 700, and the mortality increased to 36.18/100 000, while the DALY attributed to drinking increased to 17.2651 million person-years, and the DALY rate increased by 5.16%. The disease burden attributed to drinking was higher in men than that in women, and the attributable mortality and DALY rate in the elderly over 70 years old were higher than those in the young. From 1990 to 2019, the attributable disease burden of esophageal cancer was the highest in China, followed by colorectal cancer. Compared with the world and different SDI regions, China had the lowest standardized DALY rate attributed to drinking. Conclusion Drinking is one of the important risk factors for related diseases and cancers in China, and effective intervention measures should be taken for key populations.