Inhibiting MMP13 Attenuates Deep Vein Thrombosis in a Mouse Model by Reducing the Expression of Pdpn.

OBJECTIVE: Matrix metalloproteinase 13 (MMP13) is an extracellular matrix protease that affects the progression of atherosclerotic plaques and arterial thrombi by degrading collagens, modifying protein structures and regulating inflammatory responses, but its role in deep vein thrombosis (DVT) has not been determined. The purpose of this study was to investigate the potential effects of MMP13 and MMP13-related genes on the formation of DVT. METHODS: We altered the expression level of MMP13 in vivo and conducted a transcriptome study to examine the expression and relationship between MMP13 and MMP13-related genes in a mouse model of DVT. After screening genes possibly related to MMP13 in DVT mice, the expression levels of candidate genes in human umbilical vein endothelial cells (HUVECs) and the venous wall were evaluated. The effect of MMP13 on platelet aggregation in HUVECs was investigated in vitro. RESULTS: Among the differentially expressed genes, interleukin 1 beta, podoplanin (Pdpn), and factor VIII von Willebrand factor (F8VWF) were selected for analysis in mice. When MMP13 was inhibited, the expression level of PDPN decreased significantly in vitro. In HUVECs, overexpression of MMP13 led to an increase in the expression level of PDPN and induced platelet aggregation, while transfection of PDPN-siRNA weakened the ability of MMP13 to increase platelet aggregation. CONCLUSIONS: Inhibiting the expression of MMP13 could reduce the burden of DVT in mice. The mechanism involves downregulating the expression of Pdpn through MMP13, which could provide a novel gene target for DVT diagnosis and treatment.

Mechanism of Yixishu lotion in the treatment of vaginitis based on network pharmacology combined with experimental validation: an experimental research study.

Objective: Yixishu lotion (YXSL) originates from the summary of traditional Chinese medicine clinical experience and constantly improves in practice in clinical validation of the exact efficacy of traditional Chinese medicine prescription. To explore the mechanism of YXSL in treating vaginitis and the potential mechanisms based on network pharmacology and experimental verification. Methods: The active components and drug-related targets of YXSL were retrieved from the TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) database, and the target was predicted by the UniProt database. Searching for genes related to 'vaginitis' disease in the GeneCards database, a total of 2581 drug targets were obtained. The interaction between proteins (PPI - protein-protein interaction) relationship was obtained by STRING database and visualized by Cytoscape software. Finally, the 'Bioconductor' installation package in R software was used to analyze the GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways of the target. Results: In this study, by the method of network pharmacology, the key active components of YXSL were flavonoids such as quercetin, apigenin, kaempferol, luteolin, ß-sitosterol; the main core proteins included MAPK14, TP53, FGF2, ESR1, MAPK3, MAPK1, VEGFA, JUN, IL-6, and the KEGG pathway was mainly involved in MAPK pathway, Th17 pathway, Malaria, TNF pathway, and other signaling pathways. Animal experiments showed that the clinical symptoms and vaginal tissue lesions of the YXSL group and the fluconazole group were improved, and the levels of TNF-α (tumor necrosis factor alpha), IL-6 (interleukin-6), MDA (malondialdehyde), SOD (superoxide dismutase), IL-4, and IFN-γ (interferon-γ) in vaginal tissue and serum were better than the model group. Conclusion: YXSL may achieve its therapeutic effect on vaginitis by reducing the inflammatory response, improving oxidative stress response, and improving body immunity, and it provides a theoretical basis for further research on its pharmacodynamic material basis and mechanism of action.

Different dose series of human papillomavirus vaccine in young females: a pair-wise meta-analysis and network meta-analysis from randomized controlled trials.

Objective: To investigate the application value of different dose of HPV vaccine in young females. Data sources: The following databases were searched: Cochrane Library, PubMed, Embase, Web of Science, SINOMED, and Wanfang Data, from the establishment of the database to August 1st, 2022. Study eligibility criteria: The inclusion criterias were: healthy young women younger than 25 years old as the research object, randomized controlled study as the research type, and the efficacy and safety of single-dose, two-dose or three-dose HPV vaccines as the intervention measures and research endpoints. Study appraisal and synthesis methods: Meta-analysis was performed to analyze the protective effects of single-dose, 2-dose and 3-dose HPV vaccine series on young females. Results: A total of eight eligible studies involving 16 publications were included. There is no difference in the immunogenicity between the 2-dose and 3-dose series within 12 months after the last dose of HPV vaccine. However, 3-dose series was better than the 2-dose series, which performed better than the single-dose vaccine, after 12 months. With respect to the prevention of HPV16/18 infection or HPV31/33/45 infection, the single-dose vaccine worked better than 2-dose or 3-dose series. Conclusions: The present study showed that the immunogenicity of low-dose HPV vaccine was significantly less, but it reduced the risk of high-risk HPV infection. The low-dose HPV vaccine series may not offer a preventive effect on cervical lesions, though it needs to be further confirmed by additional studies.

Yigong Powder regulates CXCL12/CXCR4 signaling to reduce glutamate release and prevent cognitive decline in mouse model of aging / 中国中药杂志

This study aims to explore the effect of preventive administration of Yigong Powder on the learning and memory abilities of the mouse model of aging induced by D-galactose and decipher the underlying mechanism, so as to provide a basis for the application of Yigong Powder in the prevention and treatment of cognitive decline. Forty KM mice were randomized into control, model, donepezil(1.5 mg·kg~(-1)), and high-dose(7.5 g·kg~(-1)) and low-dose(3.75 g·kg~(-1)) Yigong Powder groups. The mice in other groups except the control group were injected with D-galactose(200 g·kg~(-1)) at the back of the neck for the modeling of aging. At the same time, the mice were administrated with corresponding drugs by gavage for one month. Morris water maze was used to examine the learning and memory abilities of the mice. Hematoxylin-eosin staining was employed to observe the pathological and morphological changes of the hippocampus. The immunofluorescence assay was employed to detect the expression of ionized calcium-binding adapter molecule 1(IBA1), glial fibrillary acidic protein(GFAP), chemokine C-X-C-motif ligand 12(CXCL12), chemokine C-X-C-motif receptor 4(CXCR4) in the hippocampus and observe the positional relationship between IBA1, GFAP, and CXCR4. Western blot was employed to determine the protein levels of extracellular regulated kinase(ERK), p-ERK, and tumor necrosis factor receptor 1(TNFR1). Enzyme-linked immunosorbent assay was employed to measure the levels of glutamate and tumor necrosis factor(TNF-α) in the brain tissue and the level of TNF-α in the serum and spleen. Yigong Powder significantly shortened the escape latency, increased the times crossing platforms, and prolonged the cumulative time in quadrants of the aging mice. It alleviated the nerve cell disarrangement, increased intercellular space, and cell degeneration or death in the hippocampus and reduced the pathology score of the damaged nerve. Moreover, Yigong Powder reduced the positive area of IBA1 and GFAP, reduced the levels of TNF-α in the brain tissue, serum, and spleen, and decreased spleen index. Furthermore, Yigong Powder decreased the average fluorescence intensity of CXCL12 and CXCR4, reduced CXCR4-positive astrocytes and microglia, down-regulated the protein levels of p-ERK/ERK and TNFR1, and lowered the level of glutamate in the brain tissue. This study showed that the preventive administration of Yigong Powder can ameliorate the learning and memory decline of the D-galactose-induced aging mice by regulating the immune function of the spleen and the CXCL12/CXCR4 signaling in the brain to reduce glutamate release. However, the mechanism of Yigong San in preventing and treating dementia via regulating spleen and stomach function remains to be studied.

Research advances in bioactivity of oyster peptides / 药学实践杂志

Functional peptides refer to peptides that are beneficial to life activities or have special physiological activities, also known as bioactive peptides. Oyster is rich in protein and is a good material for developing bioactive peptides, which has great potential as a functional food and great application value in pharmaceutical and medical industry. With the development of modern biotechnology and medical technology, the method innovation of oyster peptide preparation，the absorptivity and biological activity of oyster peptide have been enhanced significantly, which lead to deep recognition of the biological function of oyster peptide and offer the boarder application prospect. The researches on the diversification activities of oyster peptides were summarized in this review, which provided clues and ideas for the development of the oyster peptide applications.

Current situation and influencing factors of post-traumatic stress disorder among firefighters in Chongqing City / 中国职业医学

{L-End}Objective To analyze the current status of post-traumatic stress disorder (PTSD) among firefighters in Chongqing City and explore its influencing factors. {L-End}Methods A total of 1 021 firefighters in Chongqing City were selected as the study subjects using the convenient sampling method. The PTSD Checklist Civilian Version was used to assess their PTSD symptom and characteristics. The Trait Coping Style Questionnaire and the Social Support Rating Scale were used to investigate coping styles and the level of social support. {L-End}Results The positive detection rate of PTSD among the study subjects was 4.6%(47/1 021), with positive detection rates of re-experiencing, avoidance/numbing, and hyperarousal symptoms of 7.0%, 9.2%, and 16.5%, respectively. The positive detection rates of re-experiencing, avoidance/numbing, and hyperarousal symptoms in the PTSD firefighters were higher than those in non-PTSD firefighters (83.0% vs 3.3%, 93.6% vs 5.1%, 100.0% vs 12.1%, respectively; all P<0.01). The results of the multivariate logistic regression analysis showed that being injured in the past six months and adopting a negative coping style were risk factors for PTSD ［odds ratio (OR) and 95% confidence interval (CI) were 2.65 (1.07-6.56) and 1.26 (1.19-1.33), respectively; both P<0.05］, while adopting a positive coping style and having a higher level of social support were protective factors for PTSD ［OR and 95%CI were 0.90 (0.85-0.95) and 0.95 (0.91-0.99), respectively; both P<0.05］. {L-End}Conclusion The incidence of PTSD among the firefighters in Chongqing City is relatively high, with symptoms mainly characterized by hyperarousal. Being injured in the past six months, coping styles, and the level of social support are influencing factors for PTSD.

The Clinical Effects of Metronidazole Vaginal Effervescent Tablets Combined with Kushen Suppository in the Treatment of Trichomonas Vaginitis.

Objective: The aim of this study was to explore the clinical effects of metronidazole vaginal effervescent tablets combined with Kushen suppository in the treatment of Trichomonas vaginitis. Methods: Ninety patients with trichomoniasis admitted to our hospital from January 2019 to January 2020 were prospectively analyzed and randomly divided into a control group (n = 45) treated with metronidazole vaginal effervescent tablets and an experimental group (n = 45) treated with Kushen suppository on top of the control group using the random number table method. The clinical effects, inflammatory factors, and microcirculation indexes were compared. We assessed patient's vaginal health by Vaginal Health Score Scale (VHS) before and after treatment and estimated their quality of life according to Generic Quality of Life Inventory-74 (GQOLI-74). A follow-up visit was conducted to compare patient's recurrence 3 months after treatment. Results: Distinctly higher total clinical effective of the experimental group compared with that of the control group was obtained (P < 0.05); the serum level of inflammatory factors of the experimental group was dramatically lower than that of the control group after treatment (P < 0.001); the experimental group experienced a favorable microcirculation index in comparison with the control group (P < 0.001); superior VHS (P < 0.001) and GQOLI-74 (P < 0.05) scores of the experimental group after treatment compared to those of the control group were observed; the recurrence rate of the experimental group 3 months after treatment was significantly decreased in comparison with that of the control group (P < 0.05). Conclusion: Metronidazole vaginal effervescent tablets combined with Kushen suppository can effectively improve the clinical symptoms of patients with trichomonas vaginitis, abate patient's inflammatory reaction, and raise their quality of life, which is worthy of promotion.

Effect of high-level fine particulate matter and its interaction with meteorological factors on AECOPD in Shijiazhuang, China.

Epidemiological evidence of the effect of high-level air pollution and its interaction with meteorological factors on the risk of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is limited. Daily data on AECOPD cases, air pollutants and meteorological factors were collected from 2015 to 2018 in Shijiazhuang. A distributed lag non-linear model (DLNM) was used to explore the lag and cumulative effect of PM2.5 on the risk of AECOPD. The effect of the interaction between PM2.5 and meteorological factors on AECOPD was estimated by a generalized additive model (GAM) and a stratification model. A total of 4766 patients with AECOPD were enrolled. After controlling for confounders, each 10 µg/m3 increase in PM2.5 led to a 5.8% increase in the risk of AECOPD on day lag 0. The cumulative effect of PM2.5 on AECOPD risk showed an increasing trend after 3 days. Similar results were observed in both smoking and non-smoking patients. There was an interaction between PM2.5 and meteorological factors, and the risk of AECOPD was higher in cold and lower humidity conditions than in other conditions. High-level PM2.5 exposure is positively associated with the risk of AECOPD onset, and the effect of PM2.5 can be modified by the temperature and relative humidity. Public health guidelines should pay close attention to AECOPD risk under the condition of high-level PM2.5 with low temperature or low humidity.

Dapagliflozin for nonalcoholic fatty liver disease: A systematic review and meta-analysis.

OBJECTIVES: A few randomized controlled trials (RCTs) have assessed the use of dapagliflozin for the treatment of nonalcoholic fatty liver disease (NAFLD). A systematic review and meta-analysis was performed to investigate the efficacy and safety of dapagliflozin in adults with NAFLD. METHODS: We performed a comprehensive literature search of PubMed, Embase, Cochrane Library, CNKI and ClinicalTrials.gov for RCTs that assessed the use of dapagliflozin in patients with NAFLD. Risk ratios and mean differences with 95% confidence intervals were used to synthesize the results. Two authors independently extracted the data, evaluated the study quality and calculated pooled estimates. RESULTS: Eleven studies involving 839 patients were included. Compared with the control conditions, dapagliflozin led to a greater decrease in alanine transaminase, aspartate transaminase, gamma-glutamyl transferase, triglyceride, body weight, body mass index, HbA1c, and fasting plasma glucose. No difference was found between the dapagliflozin and control groups in terms of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fibrosis 4 index, type IV collagen 7S, homeostatic model assessment of insulin resistance, or adverse events. CONCLUSIONS: Dapagliflozin can markedly reduce hepatic enzymes and metabolic indicators and improve body composition, indicating its potential therapeutic efficacy.

The efficacy and safety of metformin alone or as an add-on therapy to insulin in pregnancy with GDM or T2DM: A systematic review and meta-analysis of 21 randomized controlled trials.

WHAT IS KNOWN AND OBJECTIVE: Pregnant women are increasingly being exposed to metformin for conditions including gestational diabetes mellitus and type 2 diabetes mellitus. Metformin has been found to exhibit maternal to foetal transfer, and the long-term influence is uncertain. We conducted a meta-analysis to compare the efficacy and safety of metformin alone or as add-on therapy to insulin and insulin in pregnancy with gestational diabetes mellitus or type 2 diabetes mellitus. METHODS: We performed a comprehensive literature search of PubMed, Embase, Cochrane Library and ClinicalTrials.gov for randomized controlled trials (RCTs) that compared metformin to insulin in pregnancy. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were used to synthesize the results. Two authors independently extracted the data, evaluated study quality and calculated pooled estimates. RESULTS: Twenty-one studies involving 4,545 patients were included in this meta-analysis. Compared with insulin, metformin significantly reduced the risks of maternal weight gain [MD -1.51 kg, 95%CI (-1.90 kg, -1.12 kg), P < 0.00001], gestational age at birth [MD -0.12 week, 95%CI (-0.21 week, -0.02 week), P = 0.02], gestational hypertension [RR 0.63, 95%CI (0.48, 0.82), P = 0.0006], maternal hypoglycaemia [RR 0.33, 95%CI (0.15, 0.73), P = 0.006], birthweight [MD -0.13 kg, 95%CI (-0.20 kg, -0.07 kg), P < 0.0001], neonatal hypoglycaemia [RR 0.56, 95%CI (0.49, 0.64), P < 0.00001], neonatal intensive care unit admission [RR 0.73, 95%CI (0.64, 0.83), P < 0.00001], birthweight ≥4000 g [RR 0.70, 95%CI (0.59, 0.83), P < 0.0001], and large for gestational age [RR 0.83, 95%CI (0.72, 0.97), P = 0.02] and significantly increased the risk of small for gestational age [RR 1.43, 95%CI (1.08, 1.89), P = 0.01] in pregnancy. WHAT IS NEW AND CONCLUSION: Metformin may have potential benefits for pregnant women and newborns in terms of maternal and foetal outcomes. More studies with long-term follow-up of offspring exposed to metformin in utero are needed to provide evidence for the future use of metformin in pregnancy.

Characterization and phylogenetic analysis of the complete chloroplast genome of Lycopus europaeus / 药学学报

We intend to study the structural characteristics of Lycopus europaeus Linn. chloroplast genome and compare the evolutionary relationship of species from Lamiaceae with similar medicinal effects. The total DNA of Lycopus europaeus was sequenced using the Illumina Hiseq 4000 Sequencing platform and was assembled using NOVOplasty software. And then we annotated and analyzed the genome using the CPGAVAS2 online tool. We constructed the phylogenetic tree using the Stellera chamaejasme and Potentilla chinensis as the outgroup. The whole length of Lycopus europaeus chloroplast genome was 152 085 bp. A total of 132 genes were annotated including 88 protein-coding genes, 8 rRNA genes and 36 tRNA genes. Among them, 8 protein-coding genes (ndhB, rps7, rps12, rps19, rpl2, rpl23, ycf2, ycf15), 7 tRNA coding genes (trnM-CAU, trnL CAA, trnN-GUU, trnE-UUC, trnV-GAC, trnA-UGC, trnR-ACG) and 4 rRNA coding genes (rrn16s, rrn23s, rrn4.5s, rrn5s) are located in the IR region. There are 13 protein coding genes [rps16, rps19 (×2), atpF, rpoC1, rpl2 (×2), petB, petD, rpl16, ndhB (×2), ndhA] each contains one intron, two protein-coding genes (ycf3, clpP) each contain two introns, and 8 tRNA coding genes each contain one intron. A total of 34 SSRs were detected in the chloroplast genome of Lycopus europaeus. Phylogenetic analysis revealed that two species in the Lycopus genus, four species in the Dracocephalum genus, Glechoma longituba, two species in the Mentha genus and Prunella vulgari, in total 10 species are most related. The complete genome sequence of Lycopus europaeus was obtained and analyzed, which clarified the evolutional relationship between the species of Lycopus europaeus and in the Lamiaceae family.

Design and practice of SPOC mixed teaching based on MOOC in general medical courses / 中华医学教育探索杂志

Taking "count down your weight—start from 'diet'" as an example, this article discusses the design and practice of SPOC (small private online course) mixed teaching based on MOOC (massive open online course) in general medical courses. By designing teaching methods and teaching content, and using formative evaluation methods, the SPOC mixed teaching was implemented for 201 students from Sichuan University in the spring of 2020. According to the teaching evaluation and preliminary teaching effect, students generally believed that teaching resources were relatively abundant and the communication effects were generally recognized, as well as, it could significantly improve students' interest in and effect of general medical courses.

Role of blood pressure on stroke-related mortality: a 45-year follow-up study in China / 中华医学杂志(英文版)

BACKGROUND@#Hypertension is associated with stroke-related mortality. However, the long-term association of blood pressure (BP) and the risk of stroke-related mortality and the influence path of BP on stroke-related death remain unknown. The current study aimed to estimate the long-term causal associations between BP and stroke-related mortality and the potential mediating and moderated mediating model of the associations.@*METHODS@#This is a 45-year follow-up cohort study and a total of 1696 subjects were enrolled in 1976 and 1081 participants died by the latest follow-up in 2020. COX proportional hazard model was used to explore the associations of stroke-related death with baseline systolic blood pressure (SBP)/diastolic blood pressure (DBP) categories and BP changes from 1976 to 1994. The mediating and moderated mediating effects were performed to detect the possible influencing path from BP to stroke-related deaths. E value was calculated in the sensitivity analysis.@*RESULTS@#Among 1696 participants, the average age was 44.38 ± 6.10 years, and 1124 were men (66.3%). After a 45-year follow-up, a total of 201 (11.9%) stroke-related deaths occurred. After the adjustment, the COX proportional hazard model showed that among the participants with SBP ≥ 160 mmHg or DBP ≥ 100 mmHg in 1976, the risk of stroke-related death increased by 217.5% (hazard ratio [HR] = 3.175, 95% confidence interval [CI]: 2.297-4.388), and the adjusted HRs were higher in male participants. Among the participants with hypertension in 1976 and 1994, the risk of stroke-related death increased by 110.4% (HR = 2.104, 95% CI: 1.632-2.713), and the adjusted HRs of the BP changes were higher in male participants. Body mass index (BMI) significantly mediated the association of SBP and stroke-related deaths and this mediating effect was moderated by gender.@*CONCLUSIONS@#In a 45-year follow-up, high BP and persistent hypertension are associated with stroke-related death, and these associations were even more pronounced in male participants. The paths of association are mediated by BMI and moderated by gender.

[Allergen Analysis of 4622 Children with Allergic Diseases in Shaanxi Province].

OBJECTIVE: To study the distributional characteristics of allergens in children with allergic diseases in Shaanxi province. METHODS: A total of 4 622 children diagnosed with allergic diseases in the Asthma Center, Department of Pediatrics, Xijing Hospital from March 2015 to February 2019 were selected. Serum allergen-specific immunoglobulin E (sIgE) of 19 common kinds of allergens were examined with enzyme-linked immunosorbent assay (ELISA). The children were divided into different groups according to sex, age and geographical regions, and the distributional characteristics of allergens of the different groups were compared. RESULTS: The overall positive rate for the 19 allergens of the 4 622 children was 62.8%. The ranking of the positive rates for individual allergens from high to low were as follows: 24.2% for milk, 18.0% for mold mix, 16.7% for dog dander, 16.4% for house dust mite, 11.7% for cat dander, 10.7% for cashew, 10.6% for weed pollen, 8.8% for egg white, 7.8% for house dust, 7.7% for tree pollen, 5.6% for amaranth, 4.9% for mulberry tree, 3.6% for mango, 3.2% for beef, 2.8% for cockroach, 2.1% for crab, 1.5% for shrimp, 0.8% for pineapple, and 0.3% for shellfish. Analysis based on sex showed that the allergen positive rates in boys were higher than those in girls. Analysis by age difference showed that generally the positive rates for inhaled allergens increased along with the increase in patient age, while the positive rates for ingested allergens decreased along with the increase in patient age. Analysis by geographical regions showed that the positive rate of house dust mite in the patients from the southern part of Shaanxi, the positive rate of weed pollen in the patients from the northern part of Shaanxi and the positive rates of milk and egg white in the patients from the central part of Shaanxi were higher than those in other areas. The cluster analysis and correlation analysis showed that the 19 allergens could be roughly divided into 4 categories. There were moderate correlations among tree pollen, mulberry tree and amaranth. There were moderate correlations among mulberry tree, mango and amaranth. There was moderate correlation between shrimp and crab, and there were mild or weak correlations among most of the other allergens. CONCLUSION: Among the 4 622 children with allergic diseases in Shaanxi Province who were treated in the Asthma Center, Department of Pediatrics, Xijing Hospital, male patients showed higher sensitivity to allergens. The positive rates of inhaled allergens increased, while the positive rates of ingested allergens decreased with increase in patient age. There were regional differences in the distribution of allergens. Some allergens were correlated with each other, which may be related to cross-reaction.

Efficacy and safety of the glucagon-like peptide-1 receptor agonist oral semaglutide in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the efficacy and safety of the glucagon-like peptide-1 (GLP-1) receptor agonist (RA) oral semaglutide in the treatment of type 2 diabetes mellitus (T2DM) patients. METHODS: Randomized controlled trials comparing oral semaglutide with placebo or other antihyperglycemic agents in T2DM patients were identified by searching PubMed, Embase, Cochrane Library and ClinicalTrials.gov. Risk ratios and mean differences with 95% confidence intervals were used to synthesize the results. RESULTS: Ten relevant studies involving 8,536 patients were finally included. Compared with placebo, oral semaglutide significantly reduced hemoglobin A1c (HbA1c), body weight, fasting plasma glucose, self-measured plasma glucose (SMPG), serious adverse events and all-cause death and significantly increased the number of participants who achieved HbA1c < 7.0%. Compared with active comparators, oral semaglutide significantly reduced the level of HbA1c, body weight, and SMPG and significantly increased the number of participants who achieved HbA1c < 7.0%. Compared with placebo or active comparators, oral semaglutide did not increase the incidence of adverse events, hypoglycemia (severe or blood glucose-confirmed symptomatic), myocardial infarction, heart failure requiring hospitalization, stroke or acute pancreatitis but did increase the incidence of nausea, diarrhea and vomiting. CONCLUSIONS: Oral semaglutide has favorable efficacy and safety in the treatment of T2DM patients. Oral semaglutide may be superior to liraglutide, dulaglutide, empagliflozin and sitagliptin for T2DM patients who have obesity or poor adherence to injectable GLP-1 RAs.

Short-term vs long-term dual antiplatelet therapy after drug-eluting stent implantation in patients undergoing percutaneous coronary intervention: A systematic review and meta-analysis.

OBJECTIVE: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) is under controversial. The aim of the present systematic review and meta-analysis was to evaluate the safety and efficacy of short-term (≤6 months) DAPT vs long-term (≥12 months) DAPT after PCI with a drug-eluting stent (DES). METHODS: We systematically searched the Cochrane Library, PubMed and Embase databases to identify randomised controlled trials (RCTs) that compared short-term (≤6 months) and long-term (≥12 months) DAPT. The endpoints included major bleeding, any bleeding, death from any cause, cardiac death, myocardial infarction, stroke, stent thrombosis and target vessel revascularisation. The primary outcome was major bleeding. A fixed-effects model was used to calculate the risk ratio (RR) and 95% confidence interval (CI) of each endpoint. RESULTS: Eighteen trials involving 57,940 patients were included. Compared with long-term DAPT, short-term DAPT resulted in lower rates of major bleeding [RR 0.75, 95% CI 0.65-0.87, P = .0002] and any bleeding [RR 0.61, 95% CI 0.54-0.69, P < .00001]. No significant difference was observed in the outcomes of death from any cause, cardiac death, myocardial infarction, stroke, stent thrombosis, or target vessel revascularisation. The subgroup analysis according to different DAPT durations, mono antiplatelet therapies (MAPTs), countries and P2Y12 inhibitors produced similar outcomes as comprehensive outcomes. CONCLUSIONS: Compared with long-term DAPT, short-term DAPT did not increase the risk of ischemic complications but did reduce the risks of major bleeding and any bleeding by over 25%. This study showed that short-term DAPT could be considered for most patients after DES implantation.

H2S exposure-induced oxidative stress promotes LPS-mediated hepatocyte autophagy through the PI3K/AKT/TOR pathway.

Hydrogen sulfide (H2S), a common air pollutant and toxic gas, is detrimental to organisms and the environment. Exposure to highly concentrated H2S can induce oxidative stress and autophagy. However, the mechanism underlying the liver damage caused by H2S has not been identified. Lipopolysaccharide (LPS), the key component of endotoxin, can induce oxidative stress and autophagy. For this experiment, we used one-day-old chickens as model organisms to evaluate the effects of H2S combined with LPS on oxidative stress and autophagy. The four groups (control group, LPS group, H2S group and H2S-LPS group) were observed by electron microscopy, detected by oxidative stress kit, analyzed by quantitative real-time quantitative PCR, and analyzed by Western blot. We found that the activities of antioxidant enzymes (superoxide dismutase, antioxidant glutathione, catalase, and glutathione peroxidase) decreased in the H2S group compared to those in the control group; however, malondialdehyde levels in the H2S group increased. Molecular-level studies showed that the expression of genes associated with the PI3K/ AKT/ TOR pathways in the H2S group decreased, whereas the expression of other autophagy-related genes (Beclin1, ATG5 and the ratio of LC3-II/ LC3-I) increased compared to that in the control group. These findings suggest that H2S caused oxidative stress and induced autophagy through the PI3K/ AKT/ TOR pathway in chicken liver cells. Additionally, exposure to H2S aggravated LPS-induced oxidative stress and autophagy injury. Capsule: Aerial exposure to H2S can cause oxidative stress in chicken livers and induce autophagy through the PI3K/AKT/TOR pathway, and can aggravate LPS-induced oxidative stress and autophagy.

Biocompatibility of fibrin sealant and human corneal fibroblasts / 中华实验眼科杂志

Objective:To study the biocompatibility of fibrin sealant (FS) and human corneal fibroblasts (HCFs) obtained by small incision lenticule extraction (SMILE).Methods:The human corneal stromal tissues were selected from corneal stromal lens in 24 eyes of 12 patients underwent SMILE in the First Affiliated Hospital of Guangxi Medical University from March to April 2018.HCFs were isolated and cultured in vitro within 1 hour after the corneal stromal lens were extracted and the growth status of HCFs on FS surface was observed.HCFs were divided into 2-fold leaching solution group and normal control group, and the cells in the two groups were treated with 2-fold leaching solution or complete medium according to grouping, respectively.The apoptosis of HCFs in the two groups was observed by acridine orange (AO)/ethidium bromide (EB) double staining.The proliferation of HCFs in the two groups was assayed by methyl thiazolyl tetrazolium (MTT) method.HCFs in logarithmic phase were divided into 2-fold leaching solution group, normal control group, and the cells were treated with 2-fold leaching solution or complete medium according to grouping, respectively.In addition, a blank control group without HCFs was also set and treated with complete medium.The absorbance value and relative growth rate of HCFs in the three groups were compared.HCFs in logarithmic phase were divided into 1-fold leaching solution group, 2-fold leaching solution group and normal control group, and the cells were treated with 1-fold leaching solution, 2-fold leaching solution or complete medium culture according to grouping, respectively.The apoptosis of HCFs in the three groups was compared by Annexin V-FITC/PI flow cytometry, and the cytotoxicity of the three groups was graded.Written informed consent was obtained from each patient before the operation.The study protocol adhered to the Declaration of Helsinki and was approved by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (No.2018[022]). Results:HCFs grew well on FS surface and the morphology was normal.MTT assay showed that HCFs in the 2-fold leaching solution group and the normal control group had a similar proliferation tendency, and the toxicity index of HCFs in the 2-fold leaching solution group was graded 0-1 at 0-72 hours after changing solution.After AO/EB staining, the HCFs in the 2-fold leaching solution group and the normal control group were normal, and only a small amount of early apoptotic cells were observed.Flow cytometry showed that the apoptosis rates of the normal control group, once leaching solution group and the double leaching solution group were (4.96±1.09)%, (3.66±1.35)% and (2.88±0.66)%, respectively, with no significant difference among them ( F=2.89, P=0.13). Conclusions:FS has no cytotoxicity and has good biocompatibility with HCFs in vitro.

Correlation between white matter hyperintensities and the outcomes after reperfusion therapy in patients with acute ischemic stroke / 国际脑血管病杂志

Objective:To investigate the correlation between white matter hyperintensities (WMHs) and the outcomes after reperfusion therapy in patients with acute ischemic stroke (AIS).Methods:Patients with AIS treated with reperfusion therapy (intravenous thrombolysis, endovascular mechanical thrombectomy or bridging therapy) in the Stroke Center of Zhongshan Hospital of traditional Chinese Medicine from January 2014 to December 2019 were retrospectively enrolled. The clinical baseline data of the patients were collected. The Fazekas scale was used to evaluate the severity of WMHs according to the MRI images. At 90 d after discharge, the modified Rankin Scale was used to evaluate the outcomes. A score of ≤ 2 was defined as good outcome, and a score of >2 was defined as poor outcome. Binary multivariate logistic regression analysis was used to determine the independent risk factors for hemorrhagic transformation (HT), symptomatic intracranial hemorrhage (sICH), and poor outcomes. Results:A total of 676 patients with AIS treated with reperfusion therapy were enrolled. Among them, 506 patients (74.9%) were complicated with WMHs, and 80 (11.8%) had severe WMHs. One hundred and thirty-two patients (19.5%) had HT, 34 (5.0%) had sICH, and 306 (45.3%) had a poor outcome. Multivariate logistic regression analysis showed that severe WMHs was an independent risk factor for the occurrence of HT (odds ratio [ OR] 1.890, 95% confidence interval [ CI] 1.047-3.413; P=0.035) and poor outcomes ( OR 3.366, 95% CI 1.567-7.232; P=0.002) after reperfusion treatment in patients with AIS, but there was no independent correlation with sICH ( OR 8.403, 95% CI 0.891-79.294; P=0.063). Conclusion:Severe WMHs is an independent risk factor for the occurrence of HT and poor outcomes in patients with AIS after reperfusion treatment, but it has no independent correlation with sICH.