Changes in respiratory tract and gut microbiota in AR mice and their relationship with Th1/Th2/Treg.

BACKGROUND: The etiology of allergic rhinitis (AR) is not fully understood. Studies have shown that the maturation of children's immune systems is closely related to microecology. However, few studies have focused simultaneously on changes in respiratory and gut microbiota in AR and their correlation between microecological changes and Th1/Th2/Treg. OBJECTIVE: The aim is to investigate the pathogenesis of AR based on respiratory microecology, gut microecology, and Th1/Th2/Treg levels by applying microbiome techniques and correlation analysis. METHODS: Standardized OVA-induced AR mice were established. Serum OVA-sIgE, IL-4, IFN-γ, IL-10 were measured by ELISA, Tregs in lymph nodes were determined by flow cytometry, and the histological characteristics of nasal tissues were evaluated by Hematoxylin & Eosin (H&E). Nasal symptoms were observed to determine the reliability of the AR mouse model. Nasal lavage fluid (NALF) and fecal samples were collected after the last OVA challenge. The composition of respiratory microbiota in NALF and gut microbial in feces samples via 16S rRNA gene sequencing between the two groups, further explored the relationship between microbiota and Th1/Th2/Treg levels. RESULTS: In the AR group, the incidence of nose rubbing and sneezing in each mouse was significantly increased compared with the control group (all P < 0.001) and the inflammatory cell infiltration of NALF shows a significant increase in eosinophilic and neutrophilic infiltrates upon the AR group; H&E showed that the nasal mucosa of AR mice infiltration of massive eosinophils cells and neutrophils cells. OVA-sIgE and IL-4 in the AR group were increased (P < 0.01, P < 0.05) and IFN-γ, IL-10 were significantly decreased (P < 0.01, P < 0.05). Tregs showed a downward trend in the AR group, but there was no statistical difference. Compared with the control group, the respiratory microbiota of AR mice did not change significantly, while the gut microbiota changed significantly. In gut microbiota, compared to the control group, Shannon index in the AR group revealed a significant decrease at the genus level (P < 0.01), and Simpson index was significantly increased at all levels (all P < 0.05). PCoA also showed significant differences in beta diversity between the two groups (all P < 0.05). Compared to the control group, Deferribacteres at phylum level, Roseburia, Ruminiclostridium, Anaerotruncus at genus level were significantly decreased in the AR group (all P < 0.05). Spearman's rank correlation showed that OVA-sIgE was positively correlated with Bacteroidetes, Muribaculaceae and Erysipelotrichaceae (all P < 0.05); IL-4 was significantly negatively correlated with Epsilonbacteraeota and Deferribacteres (all P < 0.05). Treg was significantly positively correlated with Patescibacteria, Lachnospiraceae, and Saccharimonadaceae in gut microecology. CONCLUSION: Our results showed that the respiratory microbiota of AR mice was not significantly altered, but the gut microbiota varied significantly and there was a correlation between gut microbiota and Th1/Th2/Treg.

Correlation of vascular endothelial growth factor with survival and pathological characteristics of patients with osteosarcoma: A systematic review and meta-analysis.

OBJECTIVE: This study aimed to assess the prognostic role of vascular endothelial growth factor (VEGF) expression in osteosarcoma. METHODS: Systematic searches of PubMed, Embase, CINAHL, Cochrane Library, ScienceDirect, and Web of Science were conducted. The correlation between VEGF expression and patients' survival was our primary endpoint. The secondary endpoints were the associations between VEGF level and patients' sociodemographic and pathological characteristics. The pooled hazard ratio (HR) or odd ratio (OR) and corresponding 95% confidence intervals (CIs) were obtained to assess the associations between VEGF expression and the target factors. Subgroup and meta-regression analyses were conducted to explore potential factors that associated with VEGF efficacy. RESULTS: The combined HR suggested that a positive VEGF status has a negative impact on overall survival (OS) (HR = 2.58; 95% CI, 2.09-3.19; P < 0.0001) and disease-free survival (DFS) (HR = 2.54; 95% CI, 1.84-3.50; P < 0.0001) in patients with osteosarcoma. Meta-regression analysis ruled out the influence of cut-off value, disease stage, histological subtype, disease grade, tumour location, geographic area, publication year, and method of HR acquisition on heterogeneity. Results showed that VEGF expression was closely correlated with tumour staging, chemotherapy response, and metastasis. CONCLUSION: Based on the study results, VEGF could serve as an effective biomarker of prognosis in patients with osteosarcoma. Besides, VEGF was related to increased tumour malignancy, which might help guide clinical decision-making regarding therapy and outcomes.

Management Practices of Head and Neck Cancer in Chinese Tertiary Care Hospitals: A Multicenter Questionnaire-Based Survey Among Oncologists.

This survey was conducted to determine the head and neck cancer (HNC) treatment strategies followed by oncologists in Chinese hospitals. It was a questionnaire-based survey, conducted from October 2017 to January 2018 in 100 random tertiary hospitals in 21 cities of China to elicit information from oncologists on the management practices for treating HNC in China. A validated, structured questionnaire was used for formal investigation with oncologists. The questions regarding HNC types, treatment strategies used for locally advanced head and neck cancer (LA HNC) and recurrent/metastatic head and neck cancer (r/m HNC), diagnosis and prognostic factors were included. The results were presented as percentages. Among the 272 oncologists, 93.4% were from tertiary care hospitals, with 35.3% and 36.4% patients from radiotherapy (RT) and oncology department, respectively. Nasopharyngeal carcinoma was the most commonly treated type of HNC according to 65.1% oncologists. Patients aged >75 years have worse prognosis and 65% oncologists corroborated that age of the patients influences treatment decision. Most of the oncologists (77.6%) preferred chemotherapy (CT) + anti-epidermal growth factor receptor targeted therapy as the first-line therapy for r/m HNC. Approximately 95% of oncologists considered induction chemotherapy (ICT) to retain organ functions and tumor shrinkage and 43.4% preferred ICT followed by chemoradiotherapy or ICT combined with RT followed by targeted therapy for LA HNC. For the management of HNC, Chinese oncologists recommended ICT with RT and targeted therapy for LA HNC and CT regimen combined with targeted therapy for r/m HNC.

Oral administration of Clostridium butyricum CGMCC0313-1 reduces ovalbumin-induced allergic airway inflammation in mice.

BACKGROUND AND OBJECTIVE: Probiotic bacteria can induce immune regulation or immune tolerance in patients with allergic diseases, but the underlying mechanisms are still unclear. There has been a growing interest in the use of beneficial bacteria for allergic diseases recently. This study aimed at exploring whether Clostridium butyricum CGMCC0313-1 (C. butyricum) can reduce ovalbumin (OVA)-induced allergic airway inflammation in a mouse model. METHODS: Mouse model of allergic airway inflammation induced via OVA was used in this study. C. butyricum was administered daily by the oral route during or after the sensitization. Airway function, pulmonary airway inflammation, mast cell degranulation, T helper (Th)-specific and anti-inflammatory cytokines, OVA-specific Ig, matrix metalloproteinase 9 (MMP-9) and histopathological alterations were examined. RESULTS: C. butyricum significantly reduced lung resistance in the asthmatic mice. Pulmonary airway inflammation, mast cell degranulation, airway remodelling and the expression of OVA-specific IgE/G1 were suppressed by oral C. butyricum. It also reversed the imbalance of Th1/Th2 and increased the anti-inflammatory cytokine IL-10. CONCLUSION: C. butyricum reduces OVA-induced allergic airway inflammation in mice and might be an additional or supplementary therapy for allergic asthma.

[The role of nuclear factor-κB in endothelial cell inflammatory injury by intermittent hypoxia in rat with emphysema].

OBJECTIVE: To investigate mechanism underlying the role of nuclear factor Kappa B (NF-κB) which induced inflammatory injury and functional lesions of aortic endothelial cells in rat with emphysema and intermittent hypoxia. METHODS: Sixty male Wistar rats were divided randomly into 4 experimental groups (n = 15 each group): control group, emphysema group, intermittent hypoxia (IH) group, emphysema with intermittent hypoxia group. The rats in control group had ad libitum access to food and water under normal circumstance. The rats in the emphysema group were exposed to cigarette smoke twice daily (30 min each time). As for IH group, the rats were exposed to intermittent hypoxia circumstance (8 h/day). Both cigarette smoke twice a day (30 min each time) and intermittent hypoxia circumstance (8 h/day) were imposed on the rats in emphysema with intermittent hypoxia group. All the rats were exposed for 8 weeks. Five rats were randomly selected from each group to measure the blood gas on the ninth week. We collected lung and endothelial tissues of thoracic aorta from the rest sacrificed rats, and observed the pathological changes of lung tissue through HE staining. The levels of ET-1, TNF-α and IL-8 in rat endothelial tissues of thoracic aorta were measured by ELISA testing. Nitrate reductase was used to measure the levels of NO, and RT-PCR to detect the levels of NF-κB mRNA, ICAM-1 mRNA, MMP-9 mRNA and eNOS mRNA. RESULTS: Lung pathology and blood gas results showed that the rat model of emphysema with intermittent hypoxia was established successfully. The levels of ET-1, TNF-α, IL-8 in emphysema with intermittent hypoxia group were (172.4 ± 1.6) ng/L, (104.1 ± 1.4) ng/L, (272.1 ± 3.6) ng/L respectively, significantly higher than the control group, emphysema group and intermittent hypoxia group (all P < 0.05). The level of NO was (27.07 ± 0.57) µmol/L, which was significant reduced; the expression of NF-κB mRNA, ICAM-1 mRNA, MMP-9 mRNA in emphysema with intermittent hypoxia group was significantly upregulated compared with the control goup, emphysema group and intermittent hypoxia group (all P < 0.05). The levels of eNOS mRNA expression were significantly lower than other three groups. The expression of NF-κB mRNA was positively correlated with MMP-9 mRNA level (r = 0.572, P < 0.001) and the expression of NF-κB mRNA was negatively correlated with eNOS mRNA level (r = 0.534, P < 0.001); there was no statistical difference in levels of NF-κB mRNA and eNOS mRNA expression between intermittent hypoxia and emphysema group (P > 0.05). CONCLUSION: Compared with only emphysema or intermittent hypoxia exposure, inflammatory injury of aortic endothelial cells of rats induced by emphysema with intermittent hypoxia was more serious, and may result in more serious cardiovascular complications. The activation of NF-κB pathway may be an important mechanism of its inflammatory response.

Prevalence, characteristics, and publication of discontinued randomized trials.

IMPORTANCE: The discontinuation of randomized clinical trials (RCTs) raises ethical concerns and often wastes scarce research resources. The epidemiology of discontinued RCTs, however, remains unclear. OBJECTIVES: To determine the prevalence, characteristics, and publication history of discontinued RCTs and to investigate factors associated with RCT discontinuation due to poor recruitment and with nonpublication. DESIGN AND SETTING: Retrospective cohort of RCTs based on archived protocols approved by 6 research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics and planned recruitment from included protocols. Last follow-up of RCTs was April 27, 2013. MAIN OUTCOMES AND MEASURES: Completion status, reported reasons for discontinuation, and publication status of RCTs as determined by correspondence with the research ethics committees, literature searches, and investigator surveys. RESULTS: After a median follow-up of 11.6 years (range, 8.8-12.6 years), 253 of 1017 included RCTs were discontinued (24.9% [95% CI, 22.3%-27.6%]). Only 96 of 253 discontinuations (37.9% [95% CI, 32.0%-44.3%]) were reported to ethics committees. The most frequent reason for discontinuation was poor recruitment (101/1017; 9.9% [95% CI, 8.2%-12.0%]). In multivariable analysis, industry sponsorship vs investigator sponsorship (8.4% vs 26.5%; odds ratio [OR], 0.25 [95% CI, 0.15-0.43]; P < .001) and a larger planned sample size in increments of 100 (-0.7%; OR, 0.96 [95% CI, 0.92-1.00]; P = .04) were associated with lower rates of discontinuation due to poor recruitment. Discontinued trials were more likely to remain unpublished than completed trials (55.1% vs 33.6%; OR, 3.19 [95% CI, 2.29-4.43]; P < .001). CONCLUSIONS AND RELEVANCE: In this sample of trials based on RCT protocols from 6 research ethics committees, discontinuation was common, with poor recruitment being the most frequently reported reason. Greater efforts are needed to ensure the reporting of trial discontinuation to research ethics committees and the publication of results of discontinued trials.

Characterization and expression profiling of selected microRNAs in tomato (Solanum lycopersicon) 'Jiangshu14'.

Presence of selected tomato (Solanum lycopersicon) microRNAs (sly-miRNAs) was validated and their expression profiles established in roots, stems, leaves, flowers and fruits of tomato variety Jiangshu14 by quantitative RT-PCR (qRT-PCR). In addition conservation characteristics these sly-miRNAs were analyzed and target genes predicted bioinformatically. Results indicate that some of these miRNAs are specific to tomato while most are conserved in other plant species. Predicted sly-miRNA targets genes were shown to be targeted by either by a single or more miRNAs and are involved in diverse processes in tomato plant growth and development. All the 36 miRNAs were present in the cDNA of mixed tissues and qRT-PCR revealed that some of these sly-miRNAs are ubiquitous in tomato while others have tissue-specific expression. The experimental validation and expression profiling as well target gene prediction of these miRNAs in tomato as done in this study can add to the knowledge on the important roles played by these sly-miRNAs in the growth and development, environmental stress tolerance as well as pest and disease resistance in tomatoes and related species. In addition these findings broaden the knowledge of small RNA-mediated regulation in S. lycopersicon. It is recommended that experimental validation of the target genes be done so as to give a much more comprehensive information package on these miRNAs in tomato and specifically in the selected variety.

Design and Image Research of Tennis Line Examination Based on Machine Vision Analysis.

In view of the intelligent demand of tennis line examination, this paper performs a systematic analysis on the intelligent recognition of tennis line examination. Then, a tennis line recognition method based on machine vision is proposed. In this paper, the color region of the image recognition region is divided based on the region growth, and the rough estimation of the court boundary is realized. In order to achieve the effect of camera calibration, a fast camera calibration method which can be used for a variety of court types is proposed. On the basis of camera calibration, a tennis line examination and segmentation system based on machine vision analysis is constructed, and the experimental results are verified by design experiments. The results show that the machine vision analysis-based intelligent segmentation system of tennis line examination has high recognition accuracy and can meet the actual needs of tennis line examination.

ICAM-1 and VCAM-1 expression in rat aortic endothelial cells after single-walled carbon nanotube exposure.

The expanded application of carbon nanotubes and increased annual production has recently sparked public interest concerning associated and potentially adverse exposure effects. As very little is known with regard to the toxicology and underlying mechanism of the phenomena termed "single-walled carbon nanotube (SWCNT) exposure", we conducted an in depth investigation of potential SWCNT effects on cell adhesion molecule gene expression within rat aortic endothelial cells (RAECs). RAEC exposure to SWCNT induced neutrophil adhesion to the endothelial monolayer via increased ICAM-1 and VCAM-1 expression. Due to NF-kappaB's fundamental involvement in the transcriptional regulation of cell adhesion molecules, we studied NF-kappaB/P65 activation in SWCNT treated RAECs, as well as GSH and LDH as determinants of oxidative stress, a condition that influences NF-kappaB activation. Resultant data indicates SWCNT exposure induces oxidative stress, thereby altering ICAM-1 and VCAM-1 expression. SWCNT induced nuclear NF-kB/P65 translocation can be inhibited by N-acetylcysteine, indicating elevated ICAM-1 and VCAM-1 expression is mediated by oxidative stress in RAECs, and may play important inflammatory roles in SWCNT-induced vascular endothelium damage.

Synthesis and spectral characterization of EuPO4 and LaPO4:Eu nanorods.

Monoclinic monazite-type EuPO4 and LaPO4:Eu nanorods were synthesized by a microemulsion-assisted solvothermal method. Their morphologies, structures, and fluorescent properties were characterized by SEM, XRD, and photoluminescence (PL) modern analytic means, respectively. The aspect ratios of EuPO4 and LaPO4:Eu nanorods have a decreasing tendency with increasing carbon chain length of assisted surfactants. When the assisted surfactant was n-butyl alcohol, the EuPO4 exhibited nanorod morphology with diameters from 20 to 30 nm and lengths from 100 to 150 nm. When the assisted surfactant was n-pentanol, the EuPO4 nanorods had lengths between 200 and 300 nm and a diameter range similar to that of the n-butyl alcohol nanorods. When the assisted surfactant was n-hexanol and n-octyl alcohol, only elliptical EuPO4 products were obtained. The LaPO4:Eu nanorods synthesized in the presence of different assisted-surfactants exhibited elliptical morphologies with diameters of 40-60 nm and lengths of 70-110 nm. The LaPO4:Eu and EuPO4 nanorods showed a orange prominent emission peak from magnetic-dipole transition 5D0 --> F1 (593 nm) of Eu3+ ions whose sites in the EuPO4 and LaPO4:Eu nanorods have C1 symmetry. Compared with bulk LaPO4:Eu, the fine structure of the Eu-O charge transfer band has very small red shift resulting from the slight increase of the length of Eu-O bond due to nanoscale size effect.

Prognostic factors in osteosarcoma: A study level meta-analysis and systematic review of current practice.

BACKGROUND: A consensus has not yet been reached regarding the abilities of gender, age, tumor size, tumor location, histologic subtypes, and surgery in the prediction of survival in osteosarcoma. We aimed to disclose their prognostic significance by conducting a meta-analysis of all the published data from the last decade. MATERIALS AND METHODS: Electronic database searches were conducted in PubMed, Embase, and Web of Science for relevant articles published within the last ten years. The pooled hazard ratio (HR) and corresponding 95% confidence interval (CI) were obtained to evaluate the prognostic values of the target factors. RESULTS: A total of 18,126 patients from 40 studies were eventually included. Results indicated that gender (male vs. female: 1.21, 95% CI, 1.11-1.32; female vs. male: 0.85, 95% CI, 0.75-0.98), age (12-20 vs. ≤12: 1.37, 95% CI, 1.13-1.65; ≥20 vs. <20: 1.29, 95% CI, 1.08-1.55; ≥40 vs. <40: 1.63, 95% CI, 1.21-2.20; ≥50 vs. <25: 2.60, 95% CI, 1.92-3.53; ≥60 vs. <60: 1.11, 95% CI, 1.06-1.18), tumor location (non-extremities vs. extremities: 2.10, 95% CI, 1.76-2.51; proximal vs. distal femur: 3.68, 95% CI: 1.51-8.96; proximal vs. distal humerus: 3.15, 95% CI: 1.53-6.49), tumor size (≥5 vs. <5: 1.42, 95% CI, 1.09-1.86; >8 vs. ≤8: 1.55, 95% CI, 1.07-2.24; >9 vs. ≤9: 1.44, 95% CI, 1.05-1.96), chemotherapy response (poor vs. good: 2.45, 95% CI, 2.02-2.97; good vs. poor: 0.41, 95% CI, 0.34-0.48), and surgery (yes vs. no: 0.45, 95% CI, 0.36-0.57; amputation vs. salvage: 2.34, 95% CI, 1.47-3.74) were significantly associated with overall survival in osteosarcoma patients. CONCLUSION: The meta-analysis demonstrated that male patients, older age, large tumor size, non-extremity osteosarcoma, proximal osteosarcoma, poor chemotherapy response, no surgical treatment, and amputation surgery were correlated with a poor prognosis in osteosarcoma patients.

Experience of Traditional Chinese Medicine Master ZHOU Zhongying in Treating Systemic Sclerosis from the Pathogenesis of Phlegm-Stasis-Heat Junction / 浙江中医药大学学报

[Objective]To study and summarize the experience of traditional Chinese medicine Master ZHOU Zhongying in treating systemic sclerosis from the pathogenesis of phlegm-stasis-heat junction,providing references for clinical practice.[Methods]Through the clinical learning,collation and analysis of Professor ZHOU's medical cases in the treatment of systemic sclerosis,the paper elaborated his clinical thinking and experience in the treatment of systemic sclerosis,which included etiology,pathogenesis,therapy and characteristic clinical medication,and verified it with medical records.[Results]Professor ZHOU thinks the key pathogenesis is phlegm-stasis-heat junction,pathological factors of systemic sclerosis mainly include phlegm,blood stasis and heat,which can depend on each other mutually throughout the course of disease.According to the progression of the disease and the evolution of pathological factors,treatment is primarily focused on phlegm-stasis-heat junction.Phlegm and blood stasis are interrelated,obstructing the circulation of Qi-blood so as to lead to pain and swelling,the treatment should be resolving phlegm,removing blood stasis and activating meridians;phlegm and heat are lingered each other,exacerbating the progression of the condition,it is appropriate to clear away phlegm and heat so that symptoms of skin redness and swelling can be relieved;blood and heat are interweaved together,which invade the skin and joints seriously,it is advisable to expel pathogenic factors by clearing away heat and resolving blood stagnation;Yin is damaged and Qi is consumed terribly,subsequently deficiency-heat is gradually emerging,the way to solve it is to supplement Qi,nourish Yin and strengthen the body resistance to eliminate pathogenic factors.The case was diagnosed as accumulation of phlegm stasis heat,blockage of wind-dampness and deficiency of Qi and Yin by Professor ZHOU,and treated with dissipating phlegm and removing blood stasis,clearing heat and unblocking collaterals,supplementing Qi and nourishing Yin,and the recipe Baiwei Decoction combined with Qinjiao Biejia Powder modified was used.[Conclusion]ZHOU Zhongying,the traditional Chinese medicine Master,who advocates attaching importance to the pathogenesis firstly in the process of syndrome differentiation,treating systemic sclerosis from the pathogenesis of phlegm-stasis-heat junction,which plays a unique role in relief of clinical symptoms,and his experiences are worthy of inheritance and promotion.

Seven thyroid imaging reporting and data systems for differentiating benign and malignant thyroid nodules under the context of Hashimoto thyroiditis / 中国医学影像技术

Objective To compare the value of 7 different thyroid imaging reporting and data systems(TI-RADS)for differentiating benign and malignant thyroid nodules under the context of Hashimoto thyroiditis(HT).Methods A total of 338 thyroid nodules in 200 HT patients were enrolled,including 167 benign and 171 malignant ones.Kwak-TIRADS,American Thyroid Association(ATA)guideline,American Association of Clinical Endocrinologists(A ACE)/American College of Endocrinology(ACE)/Associazione Medici Endocrinologi(AME)guideline,K-TIRADS of Korean Society of Thyroid Radiology,EU-TIRADS of European Thyroid Association,American College of Radiology(ACR)-TIRADS and 2020 Chinese guidelines for malignant risk stratification of thyroid nodules by ultrasound proposed by the superficial organs and vessels group of the ultrasound medicine branch of the Chinese Medical Association(C-TIRADS)were used for grading of benign and malignant thyroid nodules.Taken pathological results as gold standards,the diagnostic efficacy of 7 kinds of TI-RADS were analyzed.Results The sensitivity of Kwak-TIRADS,ATA guideline,A ACE/ACE/AME guideline,K-TIRADS,EU-TIRADS,ACR-TIRADS and C-TIRADS for differentiating benign and malignant thyroid nodules under the context of HT was 97.08％,98.25％,99.42％,95.91％,99.42％,90.06％and 99.42％,respectively,the specificity was 88.02％,83.23％,82.04％,88.02％,82.04％,86.83％and 84.43％,respectively,and the area under the curve(AUC)was 0.946,0.913,0.907,0.934,0.909,0.916 and 0.960,respectively.The sensitivity of C-TIRADS,EU-TIRADS and A ACE/ACE/AME guideline were all higher than that of K-TIRADS and ACR-TIRADS(all P＜0.05),and the specificity of Kawk-TIRADS and K-TIRADS were both higher than that of C-TIRADS,ATA guideline,EU-TIRADS and AACE/ACE/AME guideline(all P＜0.05),while AUC of C-TIRADS and Kawk-TIRADS were both higher than that of the rest 5 kinds of TI-RADS(all P＜0.05).According to Kwak-TIRADS,ATA guideline,AACE/ACE/AME guideline,K-TIRADS,EU-TIRADS,ACR-TIRADS and C-TIRADS,the malignant rate of different grades nodules identified with the same TI-RADS were significant different(all P＜0.05),which all raised with the increase of TI-RADS grade.Conclusion C-TIRADS and Kawk-TIRADS had better value for differentiating benign and malignant thyroid nodules under the context of HT,among which C-TIRADS had higher sensitivity and Kawk-TIRADS had higher specificity.

Catalpol from Rehmannia glutinosa regulates senescence in ATDC5 chondrocytes / 中国组织工程研究

BACKGROUND:The results of in vivo and in vitro studies showed that catalpol from Rehmannia glutinosa can significantly reduce the level of inflammatory indexes in the synovial tissue of rats with knee osteoarthritis,and meanwhile,it can delay the progression of knee osteoarthritis.But whether catalpol from Rehmannia glutinosa affects chondrocyte senescence and then delay the progression of knee osteoarthritis has not yet been clarified. OBJECTIVE:To investigate investigate whether catalpol from Rehmannia glutinosa could regulate ATDC5 chondrocyte senescence and the possible mechanisms. METHODS:ATDC5 chondrocytes were divided into blank group(0.1%bovine serum albumin),model group(0.1%bovine serum albumin+1 μmol/L adriamycin),low-dose catalpol group(0.1%bovine serum albumin+1 μmol/L adriamycin+20 μmol/L catalpol from Rehmannia glutinosa)and high-dose catalpol group(0.1%bovine serum albumin+1 μmol/L adriamycin+80 μmol/L catalpol from Rehmannia glutinosa).Adriamycin-induced ATDC5 chondrocyte senescence model was constructed,and the corresponding treatments were given according to the above groups.Cell counting kit-8 assay was used to detect the effects of catalpol from Rehmannia glutinosa on ATDC5 chondrocyte viability,and to screen the optimal concentration of catalpol from Rehmannia glutinosa.The senescence of ATDC5 chondrocytes in each group was detected by β-galactosidase staining after the corresponding treatments.Real-time fluorescence quantitative PCR and western blot were used to detect the mRNA and protein expression of P21,P53,type II collagen,matrix metalloproteinase 13,and interleukin-6.Immunofluorescence method was used to detect the expression of P21,P53 and type II collagen.Flow cytometry was used to detect apoptosis in each group. RESULTS AND CONCLUSION:ATDC5 chondrocytes were identified to be successfully induced and senescence model was induced.Catalpol from Rehmannia glutinosa at the concentrations of 0,20,40,and 80 μmol/L showed no significant effects on the cell viability,suggesting that catalpol from Rehmannia glutinosa is non-cytotoxic and can be used safely(P>0.05);when the concentration was≥100 μmol/L,the cell viability was reduced,suggesting that there may be cytotoxic.Therefore,80 μmol/L was chosen as the high dose for subsequent experiments in this study.The percentage of positive cells in the model group was(86.93±2.18)%,which was significantly higher than that in the blank group[(17.32±0.72)%;P<0.05].Compared with the model group,the percentage of positive cells was significantly lower in the low-and high-dose catalpol groups[(57.28±1.73)%and(27.18±0.97)%,respectively;both P<0.05].Compared with the model group,the relative expression of P21,P53,matrix metalloproteinase 13,and interleukin-6 at mRNA and protein levels was significantly downregulated in the low-and high-dose catalpol groups,while the relative expression of type II collagen at mRNA and protein levels was significantly upregulated in both groups(P<0.05),especially in the high-dose catalpol group(P<0.05).Compared with the model group,the fluorescence intensities of P21 and P53 were significantly weakened in the low-and high-dose catalpol groups,while the fluorescence intensity of type II collagen was significantly enhanced in the low-and high-dose catalpol groups(P<0.05),especially in the high-dose catalpol group(P<0.05).The cell apoptosis detected by Annexin V/PI method showed that there was no significant difference between the model group and the blank group(P>0.05);compared with the model group,the apoptotic index was significantly elevated in the low-and high-dose catalpol groups,especially in the high-dose catalpol group(P<0.05).To conclude,catalpol from Rehmannia glutinosa can slow the progression of osteoarthritis by promoting apoptosis of senescent ATDC5 chondrocytes,further removing senescent ATDC5 chondrocytes,and decreasing the senescence-associated phenotypes.

Clinical and pathological analysis of 345 cases of vulvar lichen sclerosus and a preliminary study on the frequency of maintenance treatment / 中华妇产科杂志

Objective: To analyze and summarize the clinical and pathological characteristics, management, and efficacy of patients with vulvar lichen sclerosus (VLS) through a single center large sample study, and preliminarily to explore the frequency of maintenance treatment medication for VLS. Methods: The clinical data of VLS patients in Obstetrics and Gynecology Hospital of Fudan University from 2018 to 2021 were retrospectively collected. The clinicopathological characteristics (patients' age, course of disease, complicated disease history, family history, symptoms, signs and pathology), treatment and effects were retrospectively analyzed. The patients in the maintenance treatment stage were followed up regularly to explore the minimum frequency of individual medication to maintain the stability of the disease. Results: (1) General situation: a total of 345 patients with VLS were included in this study. The average age was (50.4±14.7) years (ranged from 8 to 84 years old), prevalence was highest in the 50-59 years group (30.1%, 104/345). Immune diseases occurred in 18.6% (33/177) of patients, 24.3% (43/177) of patients had allergic skin diseases, and 5.6% (10/177) of the patients' immediate family members had chronic vulvar pruritus or vulvar hypopigmentation. (2) Clinical features: the most common symptom was vulvar pruritus (96.1%, 196/204) among 204 patients with recorded symptoms. The most common sign was hypopigmentation of the vulva (96.3%, 206/214). The most common involved sites were labia minora (70.3%, 142/202), labia majora (67.8%, 137/202), and labial sulcus (59.4%, 120/202). The cumulative number of sites involved in 62 vulvar atrophy patients (2.7±1.1) was significantly higher than that in 152 non-atrophy patients (2.2±1.0; t=3.48, P=0.001). The course of vulvar atrophy was (9.3±8.5) years, which was significantly longer than that of non-atrophy patients [(6.6±5.6) years; t=2.04, P=0.046]. (3) Pathological features: among the 286 patients with electronic pathological sections, the most common pathological feature in the epidermis was epithelial nail process passivation (71.3%, 204/286). The common pathological features in the dermis were interstitial collagenization (84.6%, 242/286), and inflammatory cell infiltration (73.8%, 211/286). (4) Treatment: 177 patients received standardized treatment after diagnosis and were followed up regularly in our hospital. In the initial treatment stage, 26.0% (46/177) of the patients were treated with 0.05% clobetasol propionate cream, and 74.0% (131/177) of the patients were treated with 0.1% mometasone furoate ointment. The complete remission rates of the two methods were respectively 80.4% (37/46) and 74.0% (97/131), and there was no statistically significant difference (χ²=0.76, P=0.385). During maintenance treatment, 27.1% (48/177) of the patients took the medication twice a week, 35.0% (62/177) took the medication once a week, and 37.9% (67/177) took the medication once every 10 days. During follow-up after 6 months of maintenance treatment, there were no patients with recurrence of pruritus or progression of vulvar signs. Conclusions: The majority of VLS patients have itching, hypopigmentation, involvement of labia minora and labia majora, progressive atrophy, and inflammatory infiltration of dermis. Local treatments of mometasone furoate and clobetasol propionate have good initial therapeutic effects. The frequency exploration of individualized maintenance treatment could minimize the occurrence of adverse reactions when ensuring the stability of the patients' condition.

A study on the job preferences and heterogeneity of medical students from different birthplaces:A discrete choice experiment based on six hospitals in Beijing / 中国卫生政策研究

Objective:To analysis the job preference and heterogeneity of medical students by distinguishing their birthplaces,and to provide reference for optimizing the management of primary health care resources.Methods:Using a cluster sampling method,an online survey of discrete choice experiment was conducted with 925 medical students from six teaching hospitals in Beijing,741 valid questionnaires were obtained,the effective recovery rate was 80.1%.The mixed logit model was used to perform regression analysis on six job attributes and estimate the willingness to pay.Results:There were significant differences in the choice of work location among medical students from different birthplaces.The subgroup results showed that compared to medical students from city,undergraduates from rural and county district preferred a work with sufficient career development opportunities.The results of undergraduate subgroup showed that undergraduates from rural district preferred a work with good environment than those from other birthplaces.Conclusion:There is heterogeneity in job preferences of medical students from different birthplaces.Policy makers should pay attention to the medical students'birthplace,also take the educational level into account to optimize the diversified job attributes,formulating targeted intervention to attract primary health care talents.

Research progress of exosome microneedle drug delivery system / 中国药房

Microneedles can penetrate the skin barrier to deliver drugs without touching the nociceptive nerves， to effectively increase the efficiency of transdermal drug delivery and improve patient compliance. Exosomes have multiple physiological functions and good biocompatibility， and are natural nanoscale drug carriers. This paper reviews the pathways and advantages of exosomes combined with microneedles for the treatment of diseases， and describes the current research status of exosome microneedle drug delivery system in various diseases. Exosome microneedles can be divided into two categories： （1） exosomes as therapeutic agents， their unique physiological origin can effectively avoid the toxicity and immunogenicity of conventional drugs and other problems； combined with microneedles directly in the specific medication site can greatly improve the metabolic consumption of oral drug delivery and patient compliance of injection drug delivery. （2） Exosomes as drug carriers， their natural vesicle structure and endogenous characteristics can protect the metabolism of foreign drugs in the body and enhance the targeting； combined with microneedles can effectively solve the problem of transdermal delivery of drugs with high efficacy but poor stability. Exosome microneedle drug delivery system is still in the laboratory stage， but it has shown great development prospects in repairing spinal cord injury， promoting diabetic ulcer wound healing， germinating， intervening myocardial infraction， relieving chronic pain and other diseases.

Interpretation of the key points of Cancer Incidence and Mortality in China, 2016 / 中国胸心血管外科临床杂志

@#In 2022, the National Cancer Center (NCC) of China reported the nationwide statistics of 2016 using population-based cancer registry data from all available cancer registries in China, which was mainly about the cancer incidence and mortality. Cancer remains a major health problem currently in our country and requires long term cooperation to deal with. This article provided a key point interpretation and analysis of cancer prevalence data in China, and provided an analysis of several main risk factors for cancer, which was conducive to the development of cancer prevention and control programs in different regions.

Anti-arrhythmic effects of kappa-opioid receptor and its changes in ischemia and reperfusion.

BACKGROUND: It remains unclear whether the kappa-opioid receptor (kappa-OR) is altered during ischemia and reperfusion. Therefore, the present study was designed to investigate changes in the kappa-OR. Additionally, the anti-arrhythmic effect induced by kappa-OR stimulation was also determined during ischemia and reperfusion (I/R). METHODS: Rats were randomly divided into different groups according to two experimental protocols. The anti-arrhythmic effects of U50,488H, a selective kappa-OR agonist, in an I/R model of 15-min ischemia were studied followed by 15 min of reperfusion. The content of kappa-OR mRNA and protein were measured by RT-PCR and Western blotting techniques in an I/R model of 30-min ischemia followed by 360 min of reperfusion. RESULTS: Limited numbers of premature ventricular contractions (PVCs) were revealed in the control group. Administration of U50,488H in the control group had no effect on occurrence of PVCs. Incidence of arrhythmia in the I/R group was significantly increased. Treated with U50,488H in the I/R group, the incidence of arrhythmia was significantly reduced. With prior use of nor-BNI, a selective kappa-OR antagonist, the anti-arrhythmic effect of U50,488H was completely blocked. Compared with the control group, the content of kappa-OR mRNA and the density of kappa-OR protein increased significantly at 0 min, 60 min, and 180 min during reperfusion. CONCLUSIONS: The present study provides evidence for the first time that the expressions of kappa-OR mRNA and protein are upregulated in the heart of I/R rats. This alteration may produce a strengthened anti-arrhythmic effect upon kappa-OR stimulation during I/R.