Objective:To explore the effects of electroacupuncture in regulating the intestinal flora of high-fat diet (HFD)-fed mice from microbiota-derived extracellular vesicles. Methods:Obese mice with established nutritional obesity model were randomly divided into either the model group (n=10) or the electroacupuncture group (n=10). Acupuncture groups were chosen to pinprick points of Zhongwan, Guanyuan, Tianshu and Zusanli. Stool samples were collected from groups at the end of the intervention and extracellular vesicles (EVs) were isolated using ultracentrifugation. The morphology of EVs isolated from the stool was confirmed by transmission electron microscopy (TEM) and analysis of the associated intestinal flora by extracting microbial DNA from them for 16S rRNA sequencing. Results:The weight and Lee's index of obese mice decreased significantly after electroacupuncture intervention treatment (P<0.01). TEM images showed that EV extracted from stools were in the form of round or oval double-membraned vesicle-like structures. The 16S rRNA sequencing analysis showed that at the phylum level, the relative abundance of Proteobacteria in the model group was significantly higher than that of the normal group (P<0.05), while the relative abundance of Frimicutes and Bacteroidetes was significantly lower than that of the normal group(P<0.05). At the genus level, expressions of Psychrobacter and Planomicrobium in the model group were significantly higher than those in the normal group (P<0.01), while expressions of Solibacillus, Solibacillus, Proteus, Lactobacillus, Agrobacterium, Enterobacter, Brevundimonas, and Comamonas were significantly lower than those in the normal group (P<0.05). After electroacupuncture intervention, the intestinal microbial diversity of experimental mice increased, and the flora structure was closer to that of normal mice. Conclusion:Structural changes in the gut flora of nutritionally obese mice accompanied by changes in gut microbial-derived EVs profiles, and 16S rRNA sequencing analysis showed that microbial DNA in gut microbial-derived EVs reflected the composition of the gut microbiota, and that electroacupuncture for the treatment of obesity was not only related to the modulation of the gut flora, but was also closely related to gut microbial-derived EVs.

Humans ; Hearing Loss/etiology* ; Lupus Erythematosus, Systemic/complications* ; Prognosis

AIM: To investigate the role and mechanism of methyltransferase-like 3(METTL3)-mediated N6-methyladenosine(m6A)methylation modification in regulating biological activity of vascular endothelial cells in the pathogenesis of choroidal neovascularization.METHODS: Human umbilical vein endothelial cells(HUVEC)cultured in vitro were divided into the following groups: control group(normal culture), low density lipoprotein(LDL)group, fluorescence-labelled LDL(Dil-LDL)group, 12.5μg/mL and 25μg/mL oxidized LDL(ox-LDL)groups, 12.5μg/mL and 25μg/mL fluorescence-labelled ox-LDL(Dil-ox-LDL)groups, DMSO group, STM2457(METTL3 inhibitor)group, DAPT group; and monkey retina-choroidal endothelial cells(RF/6A)cultured in vitro were divided into control group, DMSO group, 12.5 μg/mL ox-LDL group, and DAPT group. Endocytosed lipoprotein level was examined through fluorescence microscopy. RNA m6A methylation level was detected through a dot blot assay. Protein and RNA levels of METTL3 or angiogenesis-related markers were measured through Western blot assays and real-time quantitative polymerase chain reaction(RT-qPCR), respectively. METTL3 expression and localization were investigated through immunofluorescence. Cell migratory and tube formation capacities were assessed through transwell migration and tube formation assays, respectively.RESULTS: Endocytosed lipoprotein levels in HUVECs exposed to Dil-LDL, 12.5μg/mL and 25μg/mL Dil-ox-LDL groups were significantly higher than those in the control group. 12.5μg/mL and 25μg/mL ox-LDL groups significantly increased m6A methylation(all P<0.05), METTL3 protein expression(all P<0.01), and cell migration and angiogenesis capacities(all P<0.01). METTL3 mRNA level was significantly unregulated in the 12.5μg/mL ox-LDL group(P<0.05). In comparison to the DMSO group, the addition of STM2457 caused significant decrease in m6A methylation level(P<0.05), expression of VEGF and other angiogenesis-related markers(all P<0.05), cell migration and angiogenesis capacities(all P<0.01)and the expression of NICD(P<0.05). However, there were no significant differences in METTL3 protein and mRNA levels(all P>0.05). The expression of VEGF and NICD(all P<0.05), as well as the ability of cell migration and angiogenesis of RF/6A, was all significantly decreased in the DAPT group compared to the DMSO group(all P<0.01).CONCLUSION: METTL3-mediated m6A methylation modification promotes angiogenesis in vascular endothelial cells via the Notch signaling pathway in the pathogenesis of choroidal neovascularization.

Type 2 diabetes mellitus(T2DM), a common chronic metabolic disease, is often accompanied by internal heat syndrome. Heat-clearing prescriptions are widely used to treat different heat syndromes of T2DM from the aspects of clearing stagnant heat, excess heat, damp heat, phlegm heat, and heat toxin, demonstrating remarkable effects. The mechanism of blood sugar-lowering agents has always been a hotspot of research. Recently, the basic studies of heat-clearing prescriptions from different perspectives have been increasing year by year. To clarify the mechanisms of heat-clearing prescriptions and find specific mechanisms, we systematically reviewed the basic studies of heat-clearing prescriptions commonly used for the treatment of T2DM in the past decade, intending to provide a reference for related research.
Humans ; Diabetes Mellitus, Type 2/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Hot Temperature ; Medicine, Chinese Traditional ; Prescriptions ; Syndrome

Talent is one of the basic and strategic supports for building a modern socialist country in all aspects. Since the 1980s, the establishment of forensic medicine major and the cultivation of innovative talents in forensic medicine have become hot topics in higher education in forensic medicine. Over the past 43 years, the forensic medicine team of Shanxi Medical University has adhered to the joint education of public security and colleges, and made collaborative innovation, forming a training mode of "One Combination, Two Highlights, Three Combinations, Four in One" for innovative talents in forensic medicine. It has carried out "5+3/X" integrated reform, and formed a relatively complete talent training innovation mode and management system in teaching, scientific research, identification, major, discipline, team, platform and cultural construction. It has made a historic contribution to China's higher forensic education, accumulated valuable experience for the construction of first-class major and first-class discipline of forensic medicine, and provided strong support for the construction of the national new forensic talent training system. The popularization of this training mode is conducive to the rapid and sustainable development of forensic science, and provides more excellent forensic talents for national building, regional social development and the discipline construction of forensic science.
Humans ; Forensic Medicine/education* ; Aptitude

OBJECTIVE: To investigate the clinical efficacy of dexamethasone vitreous cavity implants (Ozurdex) for the treatment of macular edema (Irvine-Gass Syndrome) after cataract surgery. METHOD: Eight patients (eight eyes) with Irvine-Gass syndrome were enrolled for vitreous injections with Ozurdex. The patients included six men (six eyes) and two women (two eyes) with a mean age of 67.12 ± 11.92 years. Changes in the patients best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure were compared before and after treatment. RESULT: The mean visual acuity BCVA of the patients was 0.81 ± 0.26 before implantation, which improved to 0.20 ± 0.12, 0.13 ± 0.09, and 0.15 ± 0.13 at 2 weeks, 1 month, and 3 months after implantation, respectively ( P < 0.001). The patient's mean CMT before implantation was 703.00 ± 148.88 μm, and it reduced to 258.87 ± 37.40 μm, 236.25 ± 28.74 μm, and 278.00 ± 76.82 μm at 2 weeks, 1 month, and 3 months after implantation, respectively ( P < 0.001). CONCLUSION The dexamethasone vitreous cavity implant (Ozurdex) is a safe and effective treatment, which can effectively improve patient's visual acuity and reduce macular edema associated with cataract surgery.
Male ; Humans ; Female ; Middle Aged ; Aged ; Macular Edema/etiology* ; Dexamethasone/therapeutic use* ; Intraocular Pressure ; Prostheses and Implants ; Cataract

This study aimed to explore the efficacy and mechanism of combined rhein and emodin in the treatment of ulcerative colitis(UC) from the aspects of network pharmacology, animal inflammation improvement and molecular mechanism. Network pharmacology predicted that combined rhein and emodin acted on 52 potential targets, mainly participating in signaling pathways such as cancer, PI3 K/AKT, microRNAs in cancer and apoptosis. PI3 K/AKT signaling pathway has been reported to be closely related to UC, and the optimal candidate pathway for combined therapy. The UC mice model was established by dextran sodium sulfate, and then the modeled mice were randomly divided into control group, model group, rhein group, emodin group, rhein+emodin group and sulfasalazine group. After administration, compared with the conditions in model group, body weight, disease activity index(DAI) score, colon length, TNF-α, IL-6, IL-1β and myeloperoxidase(MPO) of mice in rhein+emodin group were improved(P<0.01); colonic mucosal injury was significantly reduced; the expression of p-PI3 K/PI3 K and p-AKT/AKT proteins were down-regulated(P<0.01). All the above indices were better than those in the rhein/emodin group alone. The Jin's Q-values of the effect of combined rhein and emodin on colon length, TNF-α, IL-6, IL-1β, MPO, p-PI3 K/PI3 K and p-AKT/AKT were all greater than 1.15, which indicated that there was obvious synergistic effect between rhein and emodin. In all, rhein and emodin have synergistic effect in the treatment of UC, and the mechanism may be related to the inhibition of PI3 K/AKT signaling pathway and the down-regulation of proinflammatory factors. They are the new components in the treatment of UC, which is worthy of attention.
Animals ; Anthraquinones ; Colitis, Ulcerative/metabolism* ; Colon ; Disease Models, Animal ; Emodin/pharmacology* ; Interleukin-6/metabolism* ; Mice ; Proto-Oncogene Proteins c-akt/metabolism* ; Rheum ; Tumor Necrosis Factor-alpha/metabolism*

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

Objective: To compare the application effect of the colonoscopy, fecal immunochemical test (FIT) and novel risk-adapted screening approach in colorectal cancer screening in Xuzhou population. Methods: From May 2018 to April 2019, 4 280 subjects aged 50-74 were recruited from Gulou district, Yunlong district and Quanshan district of Xuzhou. They were randomly assigned to the colonoscopy group (n=863), FIT group (n=1 723) and novel risk-adapted screening approach group (n=1 694) according to the ratio of 1∶2∶2. For the novel risk-adapted screening approach group, after the risk assessment, high-risk subjects were invited to undergo colonoscopy and low-risk subjects were invited to undergo FIT examination. All FIT positive subjects were invited to undergo colonoscopy. Colonoscopy participation rate [(the number of colonoscopies completed/the number of colonoscopies invited to participate)×100%], detection rate of colorectal lesions [(the number of diagnosed patients/the number of colonoscopies completed)×100%], colonoscopy resource load (the number of colonoscopies completed/the number of diagnosed advanced tumors) and FIT resource load in each group were calculated and compared. Results: The age of all subjects was (61±6) years old, including 1 816 males (42.43%). There was no statistically significant difference in the socio-demographic characteristics of the subjects in different screening groups. The colonoscopy participation rate was 22.60% (195/863) in the colonoscopy group, 57.04% (77/135) in the FIT group, and 33.94% (149/439) in the novel risk-adapted screening approach group, respectively. The colonoscopy participation rate was higher in the FIT group than in the colonoscopy group and the novel risk-adapted screening approach group (P<0.001). The colonoscopy participation rate of novel risk-adapted screening group was significantly higher than the colonoscopy group (P<0.001). The detection rates of advanced tumors were 6.67% (13/195), 9.09% (7/77) and 8.72% (13/149), respectively, and the difference was not statistically significant (P>0.05). The colonoscopy resource load (95%CI) was 15 (13-17) in the colonoscopy group, 11 (9-14) in the FIT group and 11 (10-13) in the novel risk-adapted screening approach group, respectively. Among them, the colonoscopy resource load of high-risk individuals in the novel risk-adapted screening approach group was 12 (9-15). FIT resource loads (95%CI) were 207 (196-218) and 88 (83-94) in the FIT group and the novel risk-adapted screening approach group. Conclusion: The combined application of risk-adapted screening approach and FIT may have a good application effect in colorectal cancer screening.
Aged ; Colonoscopy ; Colorectal Neoplasms/pathology* ; Early Detection of Cancer ; Feces ; Female ; Humans ; Male ; Mass Screening ; Middle Aged ; Occult Blood

Objective: To investigate the incidence and trend of short-term outcomes among preterm infants born <34 weeks' gestation. Methods: A secondary analysis of data from the standardized database established by a multicenter cluster-randomized controlled study "reduction of infection in neonatal intensive care units (NICU) using the evidence-based practice for improving quality (REIN-EPIQ) study". This study was conducted in 25 tertiary NICU. A total of 27 192 infants with gestational age <34 weeks at birth and admitted to NICU within the first 7 days of life from May 2015 to April 2018 were enrolled. Infants with severe congenital malformation were excluded. Descriptive analyses were used to describe the mortality and major morbidities of preterm infants by gestational age groups and different admission year groups. Cochran-Armitage test and Jonckheere-Terpstra test were used to analyze the trend of incidences of mortality and morbidities in 3 study-years. Multiple Logistic regression model was constructed to analyze the differences of outcomes in 3 study-years adjusting for confounders. Results: A total of 27 192 preterm infants were enrolled with gestational age of (31.3±2.0) weeks at birth and weight of (1 617±415) g at birth. Overall, 9.5% (2 594/27 192) of infants were discharged against medical advice, and the overall mortality rate was 10.7% (2 907/27 192). Mortality for infants who received complete care was 4.7% (1 147/24 598), and mortality or any major morbidity was 26.2% (6 452/24 598). The incidences of moderate to severe bronchopulmonary dysplasia, sepsis, severe intraventricular hemorrhage or periventricular leukomalacia, proven necrotizing enterocolitis, and severe retinopathy of prematurity were 16.0% (4 342/27 192), 11.9% (3 225/27 192), 6.8% (1 641/24 206), 3.6% (939/25 762) and 1.5% (214/13 868), respectively. There was a decreasing of the overall mortality (P<0.001) during the 3 years. Also, the incidences for sepsis and severe retinopathy of prematurity both decreased (both P<0.001). However, there were no significant differences in the major morbidity in preterm infants who received complete care during the 3-year study period (P=0.230). After adjusting for confounders, infants admitted during the third study year showed significantly lower risk of overall mortality (adjust OR=0.62, 95%CI 0.55-0.69, P<0.001), mortality or major morbidity, moderate to severe bronchopulmonary dysplasia, sepsis and severe retinopathy of prematurity, compared to those admitted in the first study year (all P<0.05). Conclusions: From 2015 to 2018, the mortality and major morbidities among preterm infants in Chinese NICU decreased, but there is still space for further efforts. Further targeted quality improvement is needed to improve the overall outcome of preterm infants.
Bronchopulmonary Dysplasia/epidemiology* ; Gestational Age ; Humans ; Infant ; Infant Mortality/trends* ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases/epidemiology* ; Patient Discharge ; Retinopathy of Prematurity/epidemiology* ; Sepsis/epidemiology*