Effect and Mechanism of Total Saponins from Panax Japonicus on White Adipose Tissue Browning/Brown Adipose Tissue Activation in High-fat Diet-induced Mice / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of total saponins from Panax japonicus （TSPJ） on white adipose tissue （WAT） browning/brown adipose tissue （BAT） activation in C57BL6/J male mice fed on a high-fat diet （HFD）. MethodThirty-two C57BL6/J male mice （8-week-old） were randomly divided into a normal group， a model group， a low-dose TSPJ group， and a high-dose TSPJ group. The mice in the low-dose and high-dose TSPJ groups were given TSPJ for four months by gavage at 25， 75 mg·kg-1·d-1， respectively， and those in the other groups were given 0.5% sodium carboxymethyl cellulose （CMC-Na） accordingly. After four months of feeding， all mice were placed at 4 ℃ for acute cold exposure， and the core body temperature was monitored. Subsequently， all mice were sacrificed， and BAT and inguinal WAT （iWAT） were separated rapidly to detect the corresponding indexes. Hematoxylin-eosin （HE） staining was used to observe the morphological changes in each group. The effect of TSPJ on the mRNA expression of uncoupling protein 1 （UCP1）， fatty acid-binding protein 4 （FABP4）， cytochrome C （CytC）， PR domain-containing protein 16 （PRDM16）， elongation of very long chain fatty acids protein 3 （ELOVL3）， peroxisome proliferator-activated receptor γ （PPARγ）， and peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α） in iWAT and BAT was detected by Real-time polymerase chain reaction （Real-time PCR）. Western blot was also used to detect the protein expression of UCP1， PRDM16， PPARγ， and PGC-1α in BAT and iWAT of each group. The effect of TSPJ on UCP1 expression in BAT and iWAT was detected by immunohistochemistry. Result① Compared with the model group， TSPJ could decrease the body weight and proportions of iWAT and BAT in the HFD-induced mice （P<0.05， P<0.01）. ② The body temperature of mice in the model group decreased compared with that in the normal group in the acute cold exposure tolerance test （P<0.05）. The body temperature in the high-dose TSPJ group increased compared with that in the model group （P<0.01）. ③ Compared with the normal group， the model group showed increased adipocyte diameter in iWAT and BAT and decreased number of adipocytes per unit area. Compared with the model group， the TSPJ groups showed significantly reduced cell diameter and increased number of cells per unit area， especially in the high-dose TSPJ group. ④ Compared with the normal group， the model group showed decreased mRNA expression of FABP4， UCP1， CytC， PRDM16， ELOVL3， PGC-1α， and PPARγ in adipose tissues of mice （P<0.05， P<0.01）. Compared with the model group， after intervention with TSPJ， the mRNA expression was significantly up-regulated （P<0.05， P<0.01）. ⑤ Compared with the normal group， the model group showed decreased protein expression of UCP1， PRDM16， PPARγ， and PGC-1α in adipose tissues of mice （P<0.05， P<0.01）. Compared with the model group， after intervention with TSPJ， the protein expression increased significantly （P<0.05， P<0.01）. ConclusionTSPJ could induce the browning of iWAT/BAT activation and enhance adaptive thermogenesis in obese mice induced by HFD. The underlying mechanism may be attributed to the activation of the PPARγ/PGC-1α signaling pathway.

Post-marketing safety surveillance and re-evaluaiton of Shu-Xue-Ning injection: a real-world study based on 30,122 cases.

Objective: This study aims to investigate the safety of Shu-Xue-Ning injection (SXNI) in real-world clinical applications. Methods: A prospective, multi-center, large-sample intensive monitoring method was used to monitor the use of SXNI in several medical institutions across China while collecting patients' dosing and adverse event information. Patients who suspected as adverse reactions made comparisons with patients who did not report adverse reactions to calculate the correlation between relevant risk factors and suspected adverse reactions. Statistical analysis software SAS 9.1 was used for data analysis. Results: A total of 48 hospitals participated in this intensive monitoring study of SXNI, and 30,122 patients were monitored from July 2015 to December 2018. A total of 1,908 adverse events were reported during the use of SXNI, with an adverse event rate of 6.33% and a 95% confidence interval (CI) of 6.06%-6.61%. Association assessment showed that 54 cases presented with SXNI-related adverse reactions with an incidence of 0.18% and a 95% CI of 0.13%-0.23%, thereby indicating that the incidence of SXNI-related adverse reactions was occasional. SXNI-related adverse reactions involved 9 systems-organs with 20 clinical manifestations, and the most common adverse reactions were rash, pruritus, and other damages of skin and its appendages. No serious adverse reactions were observed; 27.78% of the adverse reactions occurred within 30 min of drug administration and more than half of them occurred within 2 h of drug administration; 96.3% of the adverse reactions were cured or improved. Causal analysis showed that women, long dispensing time, and slow dripping speed rate were considered as risk factors. Conclusion: The incidence of SXNI-related adverse reactions in real-world clinical applications is occasional and in a reasonable range with a good prognosis.

Exosomes from miR-23 Overexpressing Stromal Cells Suppress M1 Macrophage and Inhibit Calcium Oxalate Deposition in Hyperoxaluria Rat Model.

Purpose: To investigate whether ADSC-derived miR-23-enriched exosomes could protect against calcium oxalate stone formation in a hyperoxaluria rat model. Methods: An ethylene glycol- (EG-) induced hyperoxaluria rat model and an in vitro model of COM-induced HK-2 cells coculturing with RAW264.7 cells were established to explore the protective mechanisms of ADSC-derived miR-23-enriched exosomes. Results: The results showed that treatment with miR-23-enriched exosomes from ADSCs protected EG-induced hyperoxaluria rats, and cell experiments confirmed that coculturing with miR-23-enriched exosomes alleviated COM-induced cell autophagy. Overexpressed miR-23 suppressed M1 macrophage polarization by inhibiting IRF1 expression. Furthermore, the predicted binding site between the IRF1 messenger RNA 3'-untranslated region (3'-UTR) and miR-23 was confirmed by the dual-luciferase reporter assay. Conclusion: In conclusion, our research gave the first evidence that ADSC-derived miR-23-enriched exosomes affected the polarization of M1 macrophages by directly inhibiting IRF1 and protecting against calcium oxalate stone formation in a hyperoxaluria rat model.

Analysing the current status, hotspots, and future trends of technology management: Using the WoS and scopus database.

This study presents a comprehensive overview of the development process and the latest trends in technology management (TM), laying a robust foundation for further advancements in this domain. To achieve this, we analysed 1944 TM articles from the Web of Science database and 2642 articles from Scopus, spanning the last 20 years. Employing methodologies that involve scientific knowledge graphs and bibliometrics, we analysed diverse aspects such as changes in the annual publication of articles; geographical distribution among countries, institutions, disciplines, and authors; keyword co-occurrence and clusters; and timezone view. Our findings reveal a significant surge in TM's growth in recent years, showcasing its highly promising potential. The USA is the frontrunner in contributing to TM research, followed by China and the UK. TM research is relatively concentrated in the UK, while it appears more dispersed in China. The University of Cambridge had the highest volume of research, and the disciplines of Business, Management, Engineering, and Computer Science occupied the top spots. As TM evolves, a possible challenge could be the emergence of new authoritative authors. Second, TM's vibrant landscape is characterised by hotspots such as innovation, technology strategy, technology acquisition, technology application, technology standards, and sustainable development. Among these, information and medical technologies stand out as the most frequently referenced technologies. Third, the trends in TM are as follows: innovation is subdivided into technological innovation and open innovation, bibliometric analysis and patent analysis have become pivotal methods for knowledge management, the scope of TM has expanded from internal organisational processes to encompass external aspects, and TM is gradually evolving into a mature science, with its focus transitioning from macro to micro and becoming more profound and detailed. Last, Industry 4.0, artificial intelligence, big data, and the IoT represent the latest frontier technologies in the realm of TM.

Clinical characteristics and antiviral therapy of influenza in immunosuppressed hospitalized patients / 中华临床感染病杂志

Objective:To analyse the clinical characteristics and antiviral therapy in immunosuppressed hospitalized patients with influenza.Methods:The clinical data of 273 patients with positive influenza A or B virus nucleic acid admitted in Peking University People’s Hospital from November 2015 to March 2022 were retrospectively analyzed. Among them, 123 were immunosuppressed and 150 were non-immunosuppressed. The clinical characteristics and antiviral therapy in immunosuppressed patients with influenza were analyzed. SPSS 22.0 software was used to analyze the data.Results:Chemotherapy for malignancies was the most common cause of immunosuppression (61.8%, 76/123), followed by haemopoietic stem cell transplantation (24.4%, 30/123). The common symptoms were fever (93.5%, 115/123) and cough (41.5%, 51/123). The proportions of co-infections (22.8%, 28/123) and complications (43.9%, 54/123) in immunosuppressed hospitalized patients were higher than those in non-immunosuppressed patients ( χ2=9.365 and 7.496, both P<0.01). Compared with single drug therapy, combination of antiviral drugs did not shorten the fever time, negative conversion time of virus nucleic acid and the length of hospital stay, and reduce the death ( U/ χ2=312.5, 356.0, 749.5 and 0.185, all P>0.05). Compared to patients without corticosteroids use, the use of corticosteroids did not increase mortality in immunosuppressed patients ( χ2=2.508, P=0.113). Conclusions:Classical symptoms may be absent in immunosuppressed patients with influenza, and early detection of influenza virus is still an important means of early diagnosis. Co-infections and complications are more common in immunosuppressed influenza patients. Immunosuppressed influenza patients did not benefit from the combination of antiviral therapy.

Expression and role of deleted in malignant brain tumor protein 1 in acute respiratory distress syndrome rats induced by sepsis / 中华危重病急救医学

Objective:To observe the expression of deleted in malignant brain tumor protein 1 (DMBT1) in rat acute respiratory distress syndrome (ARDS) model induced by sepsis and its relationship with ARDS related biomarkers.Methods:Forty-eight healthy male rats were randomly divided into sham operation group (Sham group) and ARDS model group, and the rats in each group were further divided into three subgroups at 6, 12 and 24 hours after operation, with 8 rats in each subgroup. The rats in the Sham group were exposed to the cecum only, and sepsis induced ARDS model was reproduced by cecal ligation and puncture (CLP) in the ARDS model group. The general performance was observed at 6, 12, 24 hours after operation. Abdominal aortic blood of rats was collected, and the levels of DMBT1, surfactant-associated protein D (SP-D), vascular endothelial growth factor (VEGF), interleukins (IL-6, IL-10) in serum were determined by enzyme-linked immunosorbent assay (ELISA). The lung tissues were collected, and the lung wet/dry weight (W/D) ratio was determined. The lung tissue pathological changes were observed under light microscope after hematoxylin-eosin (HE) staining, and the lung tissue injury score was evaluated. The expression of DMBT1 protein in lung tissue was determined by Western blotting. The relationship between the serum DMBT1 and SP-D, VEGF, IL-6, IL-10, lung tissue injury score were analyzed by Pearson correlation analysis.Results:Rats in the ARDS model group showed obvious pathological manifestations after operation. The alveolar structure destruction, inflammatory cell infiltration, and alveolar hemorrhage were observed under microscope. Compared with the Sham group, the lung tissue injury score and the lung W/D ratio at 12 hours after operation in the ARDS model group were significantly increased (lung tissue injury score: 3.35±0.13 vs. 1.16±0.07, lung W/D ratio: 5.36±0.44 vs. 4.38±0.35, both P < 0.05), and pulmonary edema was present, which suggested that the ARDS model caused by CLP was successfully reproduced. The results of ELISA and Western blotting showed that the levels of serum DMBT1, SP-D, VEGF and IL-6 in the ARDS model group increased gradually with time, while the level of IL-10 increased first and then decreased. Compared with the Sham group, the levels of DMBT1 in serum and the expressions of DMBT1 protein in lung tissue in the ARDS model group were significantly increased from 6 hours after operation [serum (ng/L) : 231.96±19.17 vs. 187.44±10.19, lung tissue (DMBT1/β-actin): 2.05±0.19 vs. 0.93±0.25, both P < 0.05], and the levels of SP-D, VEGF, IL-6 and IL-10 in serum were significantly increased from 12 hours after operation [SP-D (ng/L): 73.35±8.05 vs. 43.28±5.77, VEGF (ng/L): 89.85±8.47 vs. 43.19±5.11, IL-6 (ng/L): 36.01±2.48 vs. 17.49±1.77, IL-10 (ng/L): 84.55±8.41 vs. 39.83±5.02, all P < 0.05]. Pearson correlation analysis showed that serum DMBT1 was positively correlated with serum SP-D, VEGF, IL-6, IL-10 and lung injury score at 12 hours and 24 hours in the ARDS model group (12 hours: r values were 0.946, 0.942, 0.931, 0.936, 0.748, respectively; 24 hours: r values were 0.892, 0.945, 0.951, 0.918, 0.973, respectively; all P < 0.05). Conclusion:DMBT1 is a novel early biomarker of ARDS by affecting alveolar epithelial cell, alveolar capillary permeability and inflammatory response.

Inhibitory effects of N-acetyl-L-cysteine on brain inflammation in mice with periodontitis and Alzheimer’s disease / 西安交通大学学报(医学版)

【Objective】 To explore the effects of periodontitis on the brains of Alzheimer’s disease (AD) mice and the effects of N-acetyl-L-cysteine (NAC) on the periodontium and the brain of AD mice with experimental chronic periodontitis (CP). 【Methods】 Ten wild-type C57 mice were in the blank control group (Group C57), and another 40 3-month-old APP/PS1 transgenic mice were randomly divided into four groups: AD+CP group, AD+CP+NAC group, AD+NAC group, and AD group. The periodontitis model was established in mice in AD+CP group and AD+CP+NAC group by silk ligation. At the same time, mice in AD+CP+NAC group and AD+NAC group were injected with NAC (200 mg/kg). The height of alveolar bone loss was detected after 3 weeks, and the cell morphology of the hippocampus was observed. We determined the expression levels of NLRP3 inflammasome and amyloid-β (Aβ) in the hippocampus as well as the expression levels of interleukin (IL)-1β and IL-18 in the hippocampus and gums by ELISA. 【Results】 Compared with AD group, the height of alveolar bone loss in AD+CP group was higher (P<0.05), and the expression levels of IL-18 in the gum and IL-1β and NLRP3 in the hippocampus were increased significantly (P<0.05). In addition, compared with AD+CP group, the height of alveolar bone loss in AD+CP+NAC group was reduced significantly (P<0.05), the expression levels of IL-1β and IL-18 in the gum were reduced significantly (P<0.05) as well as the expression levels of IL-1β and Aβ in the hippocampus were reduced significantly (P<0.05). Compared with C57 group, the neurons in the hippocampus of AD+CP group were more loose and disordered, and the activation of microglia was increased, while the disarrangement of cells in AD+CP+NAC group was less than that in AD+CP group. 【Conclusion】 Periodontitis can aggravate brain inflammation in AD mice. NAC can effectively reduce alveolar bone resorption in AD mice caused by periodontitis as well as reduce the levels of inflammatory factors in the gum and hippocampus. NAC can effectively reduce the alveolar bone absorption of AD mice caused by periodontitis, reduce the level of inflammatory factors in the gingiva and hippocampus, and reduce the damage of nerve cells in the hippocampus.

Practice of Cultivating Humanistic Literacy in Public Hospitals Based on Patient Experience Improvement / 中国医学伦理学

Patient experience is an important window for modern hospital management and medical service quality, and also an important point for humanistic hospital construction. Improving patient experience is of great significance for constructing harmonious doctor-patient relationship and improving patients’ satisfaction and sense of gain. Based on the perspective of patient experience improvement, this paper analyzed the core value of "patient demand first" of Mayo Clinic and the operational experience of Cleveland Medical Center Patient Experience Office, and applied them to the cultivation of humanistic hospital culture in the First Affiliated Hospital of Xi’an Jiaotong University. Based on the concept of "strengthening patient demand orientation", with the goal of "building a high-quality patient service system and significantly improving patient satisfaction", through building education platforms for medical ethics and medical humanism, exploring the medical humanism dissemination mode for medical staff, and carrying out the humanism literacy cultivation practice in the training camp for improving hospital service efficiency, the humanistic cultural atmosphere of the hospital has been further enhanced, and the patient satisfaction has been steadily improved. It provides reference for the cultivation of humanistic literacy and the construction of new culture in public hospitals in the context of high-quality development.

Screening of endoplasmic reticulum stress signature-related genes in gastric cancer and the establishment of prognostic risk models / 肿瘤研究与临床

Objective:To screen the endoplasmic reticulum stress (ERS) signature-related differentially expressed genes (DEG) in gastric cancer and to construct a prognostic risk model based on a bioinformatics.Methods:Transcriptome sequencing data (RNA-seq) of 375 gastric cancer and 32 paracancerous tissue samples downloaded from The Cancer Genome Atlas (TCGA) database and the corresponding clinical information were obtained as training set samples; data of 387 gastric cancer patients (GSE84437) from Gene Expression Omnibus (GEO) database were downloaded as validation set samples. All data were obtained on December 25, 2021. A total of 785 ERS signature-related genes (ERS-RG) were obtained from the GeneCards database. DEG between gastric cancer tissues and paracancerous tissues in the TCGA database was analyzed. The identified gastric cancer DEG were intersected with ERS-RG from the GeneCards database to obtain gastric cancer ERS signature-related DEG, which were analyzed for gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Univariate Cox proportional risk model was used to screen ERS signature-related DEG with prognostic value in gastric cancer, and LASSO regression analysis was performed to construct a polygenic prognostic risk model, and to calculate the prognostic risk score. The patients in training set and validation set were divided into high-risk group and low-risk group according to the median of the prognostic risk score (2.369); Kaplan-Meier survival analysis was used to compare the overall survival (OS) and to draw time-dependent receiver operating characteristic (ROC) curves of patients in the two groups; nomogram was drawn based on the prognostic independent influencing factors of gastric cancer. The characteristic immune cell infiltration abundance between the two groups was analyzed by using the inverse convolution-based CIBERSORT algorithm. Cytolytic activity scores were calculated by using the geometric mean of granzyme A and perforin 1 expression. According to the median prognostic risk score (2.369) and median tumor mutation burden (TMB) (3.000), all patients with gastric cancer were divided into high risk score-high TMB group, high risk score-low TMB group, low risk score-high TMB group and low risk score-low TMB group to compare the OS of patients in each group.Results:A total of 444 ERS signature-related DEG in gastric cancer including 168 down-regulated genes and 276 up-regulated genes were obtained, which were mainly enriched in biological processes such as protein processing in the endoplasmic reticulum, extracellular matrix (ECM) receptor interactions and unfolded protein responses (all P < 0.05). Univariate Cox regression analysis showed that 12 prognostic-related ERS signature-related DEG in gastric cancer were screened out. LASSO regression analysis was performed to obtain a prognostic risk score = 0.052×NOS3+0.137×PON1+0.067×CXCR4+0.131×MATN3+0.116×ANXA5+0.090×SERPINE1. The results of Kaplan-Meier analysis showed that the OS of the low-risk group in both the training and validation sets was better than that of the high-risk group (all P < 0.01). The results of the time-dependent ROC curve analysis showed that the AUC for the 3-year, 5-year, 8-year OS rates was 0.695, 0.786, 0.698, respectively in the training set, while the AUC for the 3-year 5-year, 8-year OS rates was 0.580, 0.625, 0.627, respectively in the validation set. Multivariate Cox regression analysis showed that prognostic risk score ( HR = 3.598, 95% CI 2.290-5.655, P < 0.001) and tumor stage ( HR = 1.344, 95% CI 1.057-1.709, P < 0.05) were independent factors influencing the prognosis of gastric cancer. Among 375 gastric cancer patients in the TCGA database, the expression levels of ATF6, HSPA5, XBP1 and ATF4 in the high-risk group were higher than those in the low-risk group (all P < 0.05); CIBERSORT results showed that the abundance of activated CD4 memory T cells in the high-risk group was lower than that in the low-risk group, and the abundance of both M0 and M2 macrophages in the high-risk group was higher than that in the low-risk group (all P < 0.05). The expression levels of common immune checkpoints (CD274, CTLA4, TNFRSF9, TIGIT, PDCD1, LAG3) in the high-risk group were all higher than those in the low-risk group (all P < 0.05). Cytolytic activity score in the high-risk group was higher than that in the low-risk group ( P < 0.05). The prognostic risk score was negatively correlated with TMB ( r = -0.20, P < 0.001). Patients in the low-risk score-high TMB group had the best OS and those in the high-risk score-low TMB group had the worst OS (both P < 0.001). Conclusions:The prognostic risk score model is established based on 6 ERS signature-related DEG in gastric cancer and its prognostic risk score may be effective as an independent prognostic factor to predict the prognosis of gastric cancer patients.

Incision scar recovery assessment of patients with transaxillary dual-plane breast augmentation assisted with endoscopy / 中华医学美学美容杂志

Objective:To evaluate incision scars of transaxillary breast augmentation by different methods of scar assessment.Methods:A retrospective study was carried out on 30 patients (age range 20 to 50 years, with mean age of 32 years) who underwent endoscopic assisted transaxillary type Ⅰ dual plane breast implant augmentation by a same surgeon from August 2014 to November 2016. Scars were estimated by 3 methods which included Vancouver Scar Scale (VSS), Visual Assessment Scale (VAS) and patients' questionnaire.Results:VAS score for left side scars ranged from 0 to 8 and the median was 1. VAS score for right side scars ranged from 0 to 8.3 and the median was 1. A total of 48 scars were scored in the 0-2 point range, representing 80% of the 60 total. VSS score for left side scars ranged from 0 to 11.6 and the median was 0.8. VSS score for right side scars ranged from 0 to 11.3 and the median was 1.2. A total of 46 scars were scored in the 0-2 point range, representing 76.7% of the total 60 breats. The scores between VSS and VAS had significant statistical differences ( P<0.001). 80.0% of our patients regarded scars as unconspicuous or basically invisible in our questionnaire. Conclusions:The majority of transaxillary incision scars recover in favorable status with high patients satisfactory rate. VAS is a practical tool for evaluating transaxillary incision scars. The VSS score is not equivalent to the VAS score when grading scars only by photos.

Bibliometric analysis of diabetic retinopathy therapy based on Web of Science database / 中华眼底病杂志

Objective:To analyze the trend, hotspots and frontiers of diabetic retinopathy (DR) therapy by bibliometric method.Methods:Data were taken from the Web of Science website of Science Citation Index. Articles from 2017 to 2021, which were related to the therapy of diabetic retinopathy (DR), were included. The bibliometric analysis softwares, VOSviewer and CiteSpace were used to generate and analyze visual representations of the complex data input, including high-frequency keywords, keywords with the strongest citation bursts and co-occurrence networks of keywords.Results:A total of 3,845 articles were included. The amounts of papers published from 2017 to 2021 is 633, 651, 708, 893, and 960 respectively, increasing over years. Chinese scholars published the most articles, followed by the United States. The number of articles funded by the National Natural Science Foundation of China ranks third. There were 47 high-frequency keywords clustered into DR treatment, pathogenesis of DR, diagnosis of DR, Oxidative stress, diabetic macular edema (DME), type 2 diabetes, optical coherence tomography and deep learning. Those keywords were research hotspots and new keywords were constantly emerging. Among the top 11 burst words, the burst values of "intravitreal bevacizumab", "vascular endothelial growth factor (VEGF)", "choroidal neovascularization", "inhibition", and "receptors" were all over 10. Highly cited references showed a significant clustering tendency, which were treatment of DME, review of DR, clinical research of anti-VEGF drug therapy.Conclusions:The amount of paper related to DR therapy is on the rise; the specific treatment methods for the pathogenesis of DR are constantly research hotspots. In addition, formulating treatment strategies to reduce macular edema and other complications of diabetes, applying optical coherence tomography, deep learning and other technologies to improve the efficiency of DR diagnosis and treatment, improve targeted drug delivery systems, and finding new target points were research frontiers.

Implementation and effect evaluation of virtual simulation teaching of high performance liquid chromatography / 中华医学教育探索杂志

Objective:To study the teaching effect of traditional teaching combined with virtual simulation teaching in pharmaceutical content analysis using high performance liquid chromatography (HPLC).Methods:The students in two parallel classes of grade 2016 were divided into experimental group (44 students) and control group (38 students). Taking the content analysis and its related analytical methodology of Metronidazole by HPLC as an example, the experimental group adopted the traditional offline teaching combines with virtual simulation teaching, and the control group adopted the traditional offline teaching. The teaching effects of the two groups were compared. SPSS 22.0 was used to conduct independent-samples t-test. Results:According to the mid-term test results, the experimental group was superior to the control group in practical operation assessment [(17.98±6.75) vs. (14.03±5.92)], and the difference was statistically significant ( P < 0.05). But there were no differences between the two groups in the scores of theory, discussion report and presentation. There was no significant difference in the final exam scores between the two groups. Conclusion:The ability of practical training and the teaching effect can be improved by the teaching method of traditional offline teaching combined with virtual simulation. Through the training of this project, students have mastered the operation of HPLC, the content determination of pharmaceutical preparations, the verification of analytical methods, data processing, and the writing of analytical reports, and have certain practical analysis ability.

Health risk and spatial distribution characteristics of heavy metal exposure in typical abandoned mining area in Liuzhou, Guangxi / 环境与职业医学

Background Exposure to heavy metals has potential adverse impacts on human health, and the concentration of heavy metals in abandoned mining areas may still be higher than that in general areas, so the health risk assessment in such areas cannot be ignored. Objective To explore the health risk of heavy metal exposure and the spatial distribution characteristics of associated main metals in a typical abandoned mining area. Methods Environmental samples of irrigated soil, rice, and drinking water were collected from 13 natural villages under the jurisdiction of a township in Liuzhou, Guangxi from November to December 2019, where a typical abandoned mining was located. Finally, 13 irrigation soil samples, 11 rice samples, and 13 drinking water samples were collected. The concentrations of six metals and metalloid elements in each environmental sample were detected by inductively coupled-plasma mass spectrometry (ICP-MS), including cadmium (Cd), arsenic (As), lead (Pb), chromium (Cr), copper (Cu), and zinc (Zn). At the same time, 251 local residents were recruited for health risk assessment. Model parameters such as body weight, rice intake, and drinking water intake of local residents were obtained through field survey, and the median metal concentration of each environmental sample was taken as the risk assessment parameter of the region. The health risk of heavy metal exposure of local residents was assessed by using oral health risk assessment model of U.S. Environmental Protection Agency. The spatial distribution characteristics of health risks associated with heavy metals were evaluated by empirical Bayes interpolation method using Geographic Information System (GIS) technology. Results The positive rates of Cd, As, Pb, Cr, Cu, and Zn in the irrigated soil samples were 100.00%. The positive rate of Pb was 63.64% in the rice samples, while the rates of other metals were 100.00%. The positive rates of Cd, As, Pb, Cr, Cu, and Zn in the drinking water samples were 53.85%, 76.92%, 92.31%, 15.38%, 84.62%, and 100.00%, respectively. The results of non-carcinogenic risk assessment of oral exposure to heavy metals suggested that the contribution of heavy metals causing non-carcinogenic risk from high to low was As (70.52%) > Cd (18.03%) > Zn (6.63%) > Cu (4.12%) > Pb (0.64%) > Cr (0.06%), and the corresponding estimated non-carcinogenic risk values were 3.54 × 100, 9.05 × 10−1, 3.33 × 10−1, 2.07 × 10−1, 3.23 × 10−2, and 5.42 × 10−4, respectively. The results of carcinogenic risk assessment of oral exposure to heavy metals suggested that the contribution of studied metals from high to low was Cd (87.00%) > As (10.24%) > Cr (2.60%) > Pb (0.16%), and the estimated carcinogenic risks were 4.35× 10−3, 5.12 × 10−4, 1.30 × 10−4, and 3.08 × 10−7, respectively. Rice was the leading media associated with non-carcinogenic risk and carcinogenic risk (99.4% and 99.8% respectively). The spatial distribution characteristics of GIS showed no obvious regularity in the distribution of As in irrigated soil, rice, and drinking water. In rice and irrigated soil, the content of Cd in the villages adjacent to the mining area was obviously higher than that in the other villages, while in drinking water, the content in the villages far away from the mining area was higher. Conclusion As and Cd are the main heavy metals that increase the health risk of local residents in a typical abandoned mining area, and the distribution characteristics of the two heavy metals in different environmental media are not completely consistent.

Cystine crystal-induced reactive oxygen species associated with NLRP3 inflammasome activation: implications for the pathogenesis of cystine calculi.

PURPOSE: To investigate whether cystine crystal-induced production of reactive oxygen species (ROS) and activation of NLRP3 inflammasome contribute to cystine calculi formation. METHODS: Slc7a9-knockout rats were created as cystine calculi animal models. Kidney histological examination using TEM and immunohistochemistry were performed. The protein expression of NLRP3 and IL-1ß and the concentrations of oxidative stress markers such as ROS, MDA and H2O2 in kidney tissues were estimated. In parallel, HK-2 human renal proximal tubule cells were exposed to cystine crystals and NAC treatment. The protein and mRNA expression levels of NLRP3 were evaluated. Finally, cell apoptosis and cystine crystal adherence were also assessed. RESULTS: Activation of the NLRP3 inflammasome and marked elevations in MDA, H2O2 and ROS levels were observed both in vivo and in vitro. In particular, the protein and mRNA expression of NLRP3 was significantly increased by cystine crystals, but could be restored by an inhibitor of ROS. In addition, cell apoptosis and cystine crystal adherence were promoted by the NLRP3 inflammasome. The expression of CD44, OPN and HA in HK-2 cells was markedly increased by cystine crystals, but could be decreased by NLRP3 siRNA treatment. CONCLUSION: Notably, we found that the activation of NLRP3 by cystine crystal-induced ROS production was of major importance in the pathogenesis of cystine calculi formation.

Comprehensive analyses reveal the impacts of vaccination status and physiological variables in early infection on viral persistence in COVID-19 patients: a retrospective single-center cohort study

BACKGROUNDViral persistence is a crucial factor that influences the communicability of SARS-CoV-2 infection. However, the impacts of vaccination status and physiological variables on viral RNA shedding have not been adequately clarified. METHODSIn this study, we retrospectively collected the clinical records of 377 hospitalized COVID-19 patients, which contained unvaccinated patients and patients received two doses of an inactivated vaccine or an mRNA vaccine. Firstly, we analyzed the impacts of vaccination on disease severity and viral RNA persistence. Next, to clarify the impacts of physiological variables on viral RNA shedding in COVID-19 patients, we retrieved 49 laboratory variables and analyzed their correlations with the duration of viral RNA shedding. Finally, we established a multivariate regression model to predict the duration of viral RNA shedding. RESULTSOur results showed that both inactivated and mRNA vaccines significantly reduced the rate of moderate cases, while the vaccine related shortening of viral RNA shedding were only observed in moderate patients. Correlation analysis showed that 10 significant laboratory variables were shared by the unvaccinated mild patients and mild patients inoculated with an inactivated vaccine, but not by the mild patients inoculated with an mRNA vaccine. Moreover, we demonstrated that a multivariate regression model established based on the variables correlating with viral persistence in unvaccinated mild patients could predict the duration of viral shedding for all groups of patients. CONCLUSIONSVaccination contributed limitedly to the clearance viral RNA in COVID-19 patients. While, laboratory variables in early infection could predict the persistence of viral RNA.

Omicron booster in ancestral strain vaccinated mouse augments protective immunities against both the Delta and Omicron variants

A booster vaccination is called for constraining the evolving epidemic of SARS-CoV-2. However, the necessity of a new COVID-19 vaccine is currently unclear. To compare the effect of an Omicron-matched S DNA vaccine and an ancestral S DNA vaccine in boosting cross-reactive immunities, we firstly immunized mice with two-dose of a DNA vaccine encoding the spike protein of the ancestral Wuhan strain. Then the mice were boosted with DNA vaccines encoding spike proteins of either the Wuhan strain or the Omicron variant. Specific antibody and T cell responses were measured at 4 weeks post boost. Our data showed that the Omicron-matched vaccine efficiently boosted RBD binding antibody and neutralizing antibody responses against both the Delta and the Omicron variants. Of note, antibody responses against the Omicron variant elicited by the Omicron-matched vaccine were much stronger than those induced by the ancestral S DNA vaccine. Meanwhile, CD8+ T cell responses against both the ancestral Wuhan strain and the Omicron strain also tended to be higher in mice boosted by the Omicron-matched vaccine than those in mice boosted with the ancestral S DNA vaccine, albeit no significant difference was observed. Our findings suggest that an Omicron-matched vaccine is preferred for boosting cross-reactive immunities.

Impact of SARS-CoV-2 variants on inpatient clinical outcome

BackgroundPrior observation has shown differences in COVID-19 hospitalization rates between SARS-CoV-2 variants, but limited information describes differences in hospitalization outcomes. MethodsPatients admitted to 5 hospitals with COVID-19 were included if they had hypoxia, tachypnea, tachycardia, or fever, and data to describe SARS-CoV-2 variant, either from whole genome sequencing, or inference when local surveillance showed [≥]95% dominance of a single variant. The average effect of SARS-CoV-2 variant on 14-day risk of severe disease, defined by need for advanced respiratory support, or death was evaluated using models weighted on propensity scores derived from baseline clinical features. ResultsSevere disease or death within 14 days occurred for 950 of 3,365 (28%) unvaccinated patients and 178 of 808 (22%) patients with history of vaccination or prior COVID-19. Among unvaccinated patients, the relative risk of 14-day severe disease or death for Delta variant compared to ancestral lineages was 1.34 (95% confidence interval [CI] 1.13-1.55). Compared to Delta variant, this risk for Omicron patients was 0.78 (95% CI 0.62-0.97) and compared to ancestral lineages was 1.04 (95% CI 0.84-1.24). Among Omicron and Delta infections, patients with history of vaccination or prior COVID-19 had one-half the 14-day risk of severe disease or death (adjusted hazard ratio 0.46, IQR 0.34-0.62) but no significant outcome difference between Delta and Omicron infections. ConclusionsAlthough the risk of severe disease or death for unvaccinated patients with Omicron was lower than Delta, it was similar to ancestral lineages. Severe outcomes were less common in vaccinated patients, but there was no difference between Delta and Omicron infections.

The Role of Exosomes in Force-Related Periodontal Inflammatory Response / 医用生物力学

Exosomes are extracellular vesicles secreted by cells with a variety of molecular components, which can play the role of substance transport and signal communication between cells through autocrine and paracrine. Exosomes exist widely in vivo and participate in many physiological and pathological processes, including force-related periodontal inflammation. There are stress receptor cells in the periodontium, which can sense force loading on the tooth. An appropriate amount of mechanical loading can maintain health of the periodontium, while excessive mechanical loading may cause destruction and absorption of the periodontium, leading to periodontal inflammation. This article reviews the role of exosomes in force-related inflammation response, especially in periodontal inflammation response.

Expressions of m6A methyltransferases and their associations with microR-21 and transforming growth factor-β1 in kidney of rats exposed to cadmium / 环境与职业医学

Background Environmental pollutants can affect N6-methyladenosine (m6A) level in the body, but the change of m6A level in kidney after being exposed to cadmium (Cd) and the molecular mechanism of renal injury need to be further studied. Objective To analyze the associations of m6A modification and methyltransferases/demethylases with microRNA-21 (miR-21) and transforming growth factor- β1 (TGF - β1) in kidney of rats exposed to Cd. Methods Twenty-four SPF male SD rats were divided into 4 groups, with 6 rats in each group, and were exposed to Cd by subcutaneous injection of 2.0, 1.0, and 0.5 mg·kg−1 cadmium chloride (CdCl2) and equal volume of normal saline for 2 weeks, 7 d a week, respectively. The levels of N-acetyl-β-D-glucosidase (UNAG) and albumin (UALB) in urine, and the levels of m6A methylation and TGF-β1 in kidney were detected by enzyme-linked immunosorbent assay (ELISA). The level of blood urea nitrogen (BUN) was measured by urease method. The levels of renal oxidative stress indicators such as malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were detected by total bile acid method, water-soluble tetrazolium asssay, and colorimetric method respectively. The relative levels of TGF-β1, methyltransferases, and demethylases in kidney were measured by reverse transcription-polymerase chain reaction. The expression of miR-21 in kidney was detected by fluorescent quantitative polymerase chain reaction. Results After 2 weeks of exposure to Cd, the body weights of rats in the 2.0 and 1.0 mg·kg−1 cadmium chloride groups decreased, and the ratio of kidney/body weight and the levels of BUN, UNAG, and TGF-β1 mRNA and protein increased in the 2.0 mg·kg−1 cadmium chloride group (P<0.05). The expression levels of m6A modification, methyltransferases METTL3, METTL14, Wilms’ tumor 1-associated protein (WTAP), and miR-21 were increased both in the 2.0 and 1.0 mg·kg−1 cadmium chloride groups, with significant differences compared with the control group (P<0.05). The results of correlation analysis showed that the m6A modification level was negatively correlated with SOD (r=−0.4489, P<0.05) and GSH-Px (r=−0.4874, P<0.05), METTL3 was negatively correlated with MDA (r=−0.5158, P<0.05), while there was a positive correlation between FTO and GSH-Px (r=0.4802, P<0.05). In addition, miR-21 was positively correlated with METTL3 (r=0.7491), METTL14 (r=0.6157), and WTAP (r=0.6660) (P<0.05), TGF-β1 was positively correlated with METTL3 (r=0.5025, P<0.05) but negatively correlated with FTO (r=−0.5634, P<0.05) . Conclusion Cd can induce m6A methylation and up-regulation of METTL3, METTL14, WTAP, and miR-21 expression levels in rat kidney tissues, indicating that m6A and miR-21 may be associated with Cd-induced renal fibrosis.

Mediating effect of telomere length on relationship between lead and cadmium coexposure and blood glucose / 环境与职业医学

Background Individual lead or cadmium exposure can cause abnormal blood glucose level and changes in telomere length, and the role of telomere length in the relationship between heavy metal joint exposure and blood glucose level is still unclear. Objective To explore the role of telomere length in the relationship between lead and cadmium coexposure and blood glucose. Methods A cross-sectional study was conducted. By convenient sampling method, 600 residents living in two communities in a city in North China were selected as participants from April to June 2016. Face-to-face interviews were performed to collect general demographics and lifestyles of the participants. The peripheral blood samples of the participants were collected for blood glucose and telomere length detection, the urine samples were collected for urinary cadmium, urinary lead, and urinary creatinine measurement, and both urinary cadmium and urinary lead were corrected by urinary creatinine. The included participants were divided into a control group, a high-cadmium and low-lead group, a high-lead and low-cadmium group, and a high-lead and high-cadmium group, according to the median levels of urinary cadmium and urinary lead. A restricted cubic spline model was constructed to analyze the relationship between urinary lead/cadmium levels and blood glucose concentrations in the four groups and the relationship between cadmium exposure and telomere length in the high-lead and high-cadmium group. Intermediary model test was conducted to analyze the effect of telomere length on the relationship between exposures to lead and cadmium and blood glucose. Results The included participants were divided into the control group (n=99), the high-cadmium and low-lead group (n=91), the high-lead and low-cadmium group (n=145), and the high-lead and high-cadmium group (n=265). The differences in age, education level, per capita monthly household income, smoking, blood glucose, and telomere length were statistically significant among the four groups (P＜0.05). The high-lead and high-cadmium group had the highest blood glucose concentration, (5.63±1.68) mmol·L−1, and the shortest telomere length, (2.63±1.05) Kb. The restricted cubic spline results showed that urinary cadmium level was correlated with blood glucose concentration in the high-lead and high-cadmium group (F=3.45, P=0.037), and there was a non-linear association (F=6.91, P=0.002); the association between urinary cadmium level and telomere length was also non-linear (F=5.93, P=0.043). The intermediary model test results showed that telomere length was a mediating variable between urinary cadmium level and blood glucose concentration, and the mediating effect size was 0.0192 (95%CI: 0.0007-0.0563), with a mediation ratio of 15.57%. Conclusion Correlations between urinary cadmium and blood glucose and between urinary cadmium and telomere length were observed in the high-lead and high-cadmium coexposure group, and telomere length may play a mediating role in the relationship between them.