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1.
Article in Chinese | WPRIM | ID: wpr-928133

ABSTRACT

Neuropathic pain is one of the common complications of diabetes. Tetrahydropalmatine(THP) is a main active component of Corydalis Rhizoma with excellent anti-inflammatory and pain-alleviating properties. This study aims to investigate the therapeutic effect of THP on diabetic neuropathic pain(DNP) and the underlying mechanism. High-fat and high-sugar diet(4 weeks) and streptozotocin(STZ, 35 mg·kg~(-1), single intraperitoneal injection) were employed to induce type-2 DNP in rats. Moreover, lipopolysaccharide(LPS) was used to induce the activation of BV2 microglia in vitro to establish an inflammatory cellular model. Fasting blood glucose(FBG) was measured by a blood glucose meter. Mechanical withdrawal threshold(MWT) was assessed with von Frey filaments, and thermal withdrawal latency(TWL) with hot plate apparatus. The protein expression levels of OX42, inducible nitric oxide synthase(iNOS), CD206, p38, and p-p38 were determined by Western blot, the fluorescence expression levels of OX42 and p-p38 in the dorsal horn of the rat spinal cord by immunofluorescence, the mRNA content of p38 and OX42 in rat spinal cord tissue by qRT-PCR, and levels of nitric oxide(NO), interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and serum fasting insulin(FINS) by enzyme-linked immunosorbent assay(ELISA). RESULTS:: showed that the mo-del group demonstrated significant decrease in MWT and TWL, with pain symptoms. THP significantly improved the MWT and TWL of DNP rats, inhibited the activation of microglia and p38 MAPK signaling pathway in rat spinal cord, and ameliorated its inflammatory response. Meanwhile, THP promoted the change of LPS-induced BV2 microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, suppressed the activation of the p38 MAPK signaling pathway, decreased the expression levels of inflammatory factors NO, IL-1β, IL-6, and TNF-α, and increased the expression level of anti-inflammatory factor IL-10. The findings suggested that THP can significantly ameliorate the pain symptoms of DNP rats possibly by inhibiting the inflammatory response caused by M1 polarization of microglia via the p38 MAPK pathway.


Subject(s)
Animals , Berberine Alkaloids , Blood Glucose/metabolism , Diabetes Mellitus , Diabetic Neuropathies/genetics , Interleukin-10 , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Microglia , Neuralgia/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction , Spinal Cord/metabolism , Streptozocin/therapeutic use , Tumor Necrosis Factor-alpha/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism
2.
Article in Chinese | WPRIM | ID: wpr-928097

ABSTRACT

This study screened and analyzed the differentially expressed genes(DEGs) between colorectal cancer(CRC) tissues and normal tissues with bioinformatics techniques to predict biomarkers and Chinese medicinals for the diagnosis and treatment of CRC. The microarray data sets GSE21815, GSE106582, and GSE41657 were downloaded from the Gene Expression Omnibus(GEO), and the DEGs were screened by GEO2 R, followed by the Gene Ontology(GO) tern enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the DEGs based on DAVID. The protein-protein interaction network was constructed by STRING, and MCODE and Cytohubba plug-ins were used to screen the significant modules and hub genes in the network. UCSC, cBioPortal, and Oncomine were employed for hierarchical clustering, survival analysis, Oncomine analysis, and correlation analysis of clinical data. Coremine Medical was applied to predict the Chinese medicinals acting on hub genes. A total of 284 DEGs were screened out, with 146 up-regulated and 138 down-regulated. The up-regulated genes were mainly involved in cell cycle, NLRs pathway, and TNF signaling pathway, and the down-regulated genes were related to mineral absorption, nitrogen metabolism, and bicarbonate reabsorption in proximal tubules. The 15 hub genes were CDK1, CDC20, AURKA, MELK, TOP2 A, PTTG1, BUB1, CDCA5, CDC45, TPX2, NEK2, CEP55, CENPN, TRIP13, and GINS2, among which CDK1 and CDC20 were regarded as core genes. The high expression of CDK1 and CDC20 suggested poor prognosis, and they significantly expressed in many cancers, especially breast cancer, lung cancer, and CRC. The expression of CDK1 and CDC20 was correlated with gender, tumor type, TNM stage, and KRAS gene mutation. The potential effective medicinals against CRC were Scutellariae Radix, Scutellariae Barbatae Herba, Arnebiae Radix, etc. The significant expression of CDK1 and CDC20 can help distinguish tumor tissues from normal tissues, and is related to survival prognosis. Thus, the two can be used as biomarkers for the diagnosis and treatment of CRC. This study provides a reference for related drug development.


Subject(s)
Colorectal Neoplasms/genetics , Computational Biology/methods , Early Detection of Cancer , Gene Expression Profiling/methods , Humans , Medicine, Chinese Traditional
3.
Article in Chinese | WPRIM | ID: wpr-928052

ABSTRACT

A new iridoid glycoside, cornushmf A(1) and nine known iridoids(2-10) were isolated from the water extract of the wine-processed Corni Fructus by various column chromatographies. Their chemical structures were identified by comprehensive spectroscopic methods as 7β-O-(2″-formylfuran-5″-methylene)-morroniside(1), 7-dehydrologanin(2), sweroside(3), 7β-O-methylmorroniside(4), 7α-O-methylmorroniside(5), 7β-O-ethylmorroniside(6), 7α-O-ethylmorroniside(7), cornuside(8), sarracenin(9), and loganin(10).


Subject(s)
Cornus/chemistry , Drugs, Chinese Herbal/chemistry , Iridoids , Wine
4.
Article in Chinese | WPRIM | ID: wpr-927873

ABSTRACT

Objective To explore the potential targets of triclosan in the treatment of nonalcoholic fatty liver disease(NAFLD) and to provide new clues for the future research on the application of triclosan. Methods The targets of triclosan and NAFLD were obtained via network pharmacology.The protein-protein interaction network was constructed with the common targets shared by triclosan and NAFLD.The affinity of triclosan to targets was verified through molecular docking.Gene ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were carried out to analyze the key targets and the potential mechanism of action.NAFLD model was established by feeding male C57BL/6J mice with high-fat diet for 12 weeks.The mice were randomly assigned into a model group and a triclosan group [400 mg/(kg·d),gavage once a day for 8 weeks].The hematoxylin-eosin(HE) staining was used for observation of the pathological changes and oil red O staining for observation of fat deposition in mouse liver.Western blotting was employed to detect the protein level of peroxisome proliferator-activated receptor alpha(PPARα) in the liver tissue. Results Triclosan and NAFLD had 34 common targets,19 of which may be the potential targets for the treatment,including albumin(ALB),PPARα,mitogen-activated protein kinase 8(MAPK8),and fatty acid synthase.Molecular docking predicted that ALB,PPARα,and MAPK8 had good binding ability to triclosan.KEGG pathway enrichment showcased that the targets were mainly enriched in peroxisome proliferator-activated receptor signaling pathway,in which ALB and MAPK8 were not involved.Triclosan alleviated the balloon-like change and lipid droplet vacuole,decreased the lipid droplet area,and up-regulated the expression level of PPARα in mouse liver tissue. Conclusion PPARα is a key target of triclosan in the treatment of NAFLD,which may be involved in fatty acid oxidation through the peroxisome proliferator activated receptor signaling pathway.


Subject(s)
Animals , Liver/pathology , Male , Mice , Mice, Inbred C57BL , Molecular Docking Simulation , Network Pharmacology , Non-alcoholic Fatty Liver Disease/drug therapy , PPAR alpha/therapeutic use , Triclosan/therapeutic use
5.
Chinese Journal of Biotechnology ; (12): 666-677, 2022.
Article in Chinese | WPRIM | ID: wpr-927735

ABSTRACT

Mucic acid is a hexaric acid that can be biosynthesized by oxidation of D-galacturonic acid, which is the main constituent of pectin. The structure and properties of mucic acid are similar to that of glucaric acid, and can be widely applied in the preparation of important platform compounds, polymers and macromolecular materials. Pectin is a cheap and abundant renewable biomass resource, thus developing a process enabling production of mucic acid from pectin would be of important economic value and environmental significance. This review summarized the structure and hydrolysis of pectin, the catabolism and regulation of D-galacturonic acid in microorganisms, and the strategy for mucic acid production based on engineering of corresponding pathways. The future application of mucic acid are prospected, and future directions for the preparation of mucic acid by biological method are also proposed.


Subject(s)
Hexuronic Acids/metabolism , Pectins/metabolism , Sugar Acids/metabolism
6.
Article in Chinese | WPRIM | ID: wpr-927426

ABSTRACT

The characteristics of meridian sinew theory at the early era have been collected. It is believed that the running courses and indications of twelve meridian sinew regions in Lingshu (Miraculous Pivot) are closely associated with Zubi Shiyimai Jiujing (Moxibustion Therapy on the Eleven Meridians of Legs and Arms) and Yinyang Shiyimai Jiujing (Moxibustion Therapy on the Eleven Meridians of Yin and Yang). Due to the attachment of twelve regular meridians, the development of its own theory is blocked. Meridian sinew theory guides the diagnosis and treatment of many dominant disorders (e.g. pain disorder and bi syndrome) with acupuncture and moxibustion. The defensive qi is circulated among meridian sinews, which is the core of meridian sinew theory. The acupoint selection relies on the meridian sinew theory at the early era, such as "consolidating muscles when they involved in disorders, using painful sites as acupoints to treat diseases" "interaction of the associated muscles" and "conducting meridian qi along with the running courses of meridians". The crack needling (one of the nine needling techniques exerted between two muscles to treat muscular pain) is adopted generally to mobilize the defensive qi so as to resist pathogens, relieve the compression in foci and promote qi and blood circulation in meridians. The rational understanding of meridian sinew theory may improve the accuracy of diagnosis and treatment of meridian sinew disorders, "reduce the pressure" on meridian theory and contribute to the enrichment of the theoretical framework of acupuncture and moxibustion.


Subject(s)
Acupuncture , Acupuncture Points , Acupuncture Therapy , Meridians , Moxibustion
7.
Article in Chinese | WPRIM | ID: wpr-927401

ABSTRACT

The paper introduces professor MA Hui-fang's experience in age-related macular degeneration treated with acupuncture at Jingming (BL 1). It is believed that the basic pathogenesis of this disease refers to liver and kidney insufficiency and weakness of spleen qi. Based on the academic ideas of yang qi and meridian-collateral system, the treatment principle is proposed as "invigorating yang qi, replenishing the liver and kidney and nourishing the spleen and stomach". Regarding acupoint selection, Jingming (BL 1) is specially used, combined with the 4 front-mu points (Zhongwan [CV 12], Guanyuan [CV 4] and bilateral Tianshu [ST 25]), as well as the empirical points for eye diseases (Jingming [BL 1], Baihui [GV 20] and Zulinqi [GB 41]). Concerning to needling technique, shuci (transport needling), fenci (intermuscular needling) and yuandaoci (distal needling) are dominated. Eventually, a set of unique therapeutic method has been accumulated through professor MA Hui-fang's clinical practice in treatment of age-related macular degeneration.


Subject(s)
Acupuncture , Acupuncture Points , Acupuncture Therapy , Humans , Macular Degeneration/therapy , Meridians
8.
Article in Chinese | WPRIM | ID: wpr-927340

ABSTRACT

Regarding the development of international standard of Guideline for Clinical Practice of Acupuncture and Moxibustion: Migraine, the existing problems of the design and methodology of randomized controlled trial (RCT) on acupuncture and moxibustion for migraine were summarized in views of participant, intervention, control, outcome and study design. Four directions need to be further explored, (1) research of adolescent migraine, special subtype of migraine and migraine in a special population; (2) research of the immediate analgesic effect of acupuncture and moxibuation at the attack stage of migraine and the therapeutic effect of migraine at each stage; (3) research on safety and health economics; (4) clinical trial registration of acupuncture and moxibustion. In study, the target population should be further determined and specialized, the diagnosis criteria of western medicine and traditional Chinese medicine be generalized and concentrated, the staging and type division of disease be accurate, the intervention procedure be integrated, the control design be rationalized, the outcomes be validated, and the description of randomization and blinding be clarified.


Subject(s)
Acupuncture , Acupuncture Therapy , Adolescent , Humans , Medicine, Chinese Traditional , Migraine Disorders/therapy , Moxibustion
9.
China Pharmacy ; (12): 1165-1171, 2022.
Article in Chinese | WPRIM | ID: wpr-924067

ABSTRACT

OBJECTIVE To identify an d analyze chemical cons tituents of Pleione yunnanensis with origin of Pleione yunnanensis. METHODS UPLC-Q-Exactive-Plus-Orbitrap-MS was adopted. The determination was performed on Hyperdil GOLD column with mobile phase consisted of 0.1% formic acid solution-0.1% formic acid acetonitrile solution (gradient elution )at the flow rate of 0.3 mL/min. The column temperature was set at 40 ℃,and sample size was 2 µL. The electrospray ion source was adopted,and the scanning range was m/z 100-1 500,and the scanning mode was positive and negative ion exchange mode of full scan+ddMS2. The structure of chemical constituents were determined by using Compound Discoverer 3.1 software,comparing with mzCloud,PubChem network database and OTCML ,on the basis of reference substance and published literatures. RESULTS & CONCLUSIONS A total of 42 chemical constituents were identified (positive ion mode has 24,negative ion mode has 27), including 13 benzyl succinate glycosides (such as dactylorhin C ,coelovirin A ,militarine),4 phenol glycosides (such as adenosine , guanosine,gastrodin),3 alkaloids(choline,betaine,berberine),and one flavonoid (nobiletin),7 aromatics(such as DL-lysine , DL-arginine,DL-glutamine),one sugar (sucrose),3 benzenes(shancigusin H ,shancigusin H isomer ,batatasin Ⅲ)and 10 others (such as p-methoxybenzoic acid ,monomethyl dodecanedioate ,diphenylamine). Glucose oxybenzyl and some small mole cules are easy to be lost in the cleavage of benzyl succinate glycosides;glycosyl is easy to be lost in the cleavage of phenol glycosides;the cleavage of alkaloids mainly manifest as the cleavage and loss of small molecular substituents ;demethyla- tion reaction is occurred in most flavonoids.

10.
China Pharmacy ; (12): 923-929, 2022.
Article in Chinese | WPRIM | ID: wpr-923593

ABSTRACT

OBJECTIVE To establish the fingerprints of dried Houttuynia cordata and its decoction pieces ,conduct chemometrics analysis and determine the contents of 5 flavonoids such as neochlorogenic acid. METHODS High performance liquid chromatography (HPLC)method was adopted. Using quercitrin as reference ,HPLC fingerprints of 10 batches of dried H. cordata and its decoction pieces were drawn. The similarity evaluation was conducted by Similarity Evaluation System of TCM Chromatographic Fingerprint (2012 edition),the common peaks were also confirmed. SIMCA-P 14.1 software was applied for principal component analysis (PCA)and partial least square-discriminant analysis (PLS-DA),and the variable importance in projection(VIP)value more than 1 was considered as a standard to screen the differential components affecting the quality of these two products ;meanwhile,the contents of 5 components such as neochlorogenic acid in both products were determined by the same HPLC method. RESULTS There were 20 common peaks in 10 batches of dried H. cordata and 10 batches of its decoction pieces with the similarity values more than 0.960. A total of 5 common peaks were identified ,which were neochlorogenic acid (peak 1), chlorogenic acid (peak 3),cryptochlorogenic acid (peak 4),rutin(peak 7)and quercitrin (peak 11). The results of PCA and PLS-DA showed that dried H. cordata could be distinguished from its decoction pieces obviously ;the common peaks with VIP value greater than 1 were as follows :peak 7(rutin),peak 20,peak 5,peak 13,peak 2,peak 18,peak 3(chlorogenic acid ), peak 14,peak 17 and peak 19. The linear range of neochlorogenic acid ,chlorogenic acid ,cryptochlorogenic acid ,rutin and quercitrin were 3.77-60.29 μg/mL(r=0.999 7),1.40-22.42 μg/mL(r=0.999 5),3.76-60.22 μg/mL(r=0.999 9),2.19-35.06 μg/mL (r=0.999 9)and 25.49-407.88 μg/mL(r=0.999 7),respectively. RSDs of precision ,stability(24 h)and reproducibility E-mail:20190394@njucm.edu.cn tests were all lower than 3%. The average recoveries of the above components in these two products were 98.72%-101.12% and 98.86% -100.63% with RSDs less than 3%(n=9). In dried H. cordata ,the average contents of 5 components were 0.87,0.33,0.59,0.61 and 6.17 mg/g,while the average contents were 0.42,0.11,0.26,0.23 and 3.16 mg/g in its decoction pieces ,respectively. CONCLUSIONS HPLC fingerprint and the method of content determination are stable and feasible ,which could be used for the quality control of dried H. cordata and its decoction pieces. Besides ,rutin and other components may be the differential components which could affect the quality of these two products ;the average contents of the 5 flavonoids such as neochlorogenic acid in dried H. cordata all decrease after processing.

11.
Organ Transplantation ; (6): 371-2022.
Article in Chinese | WPRIM | ID: wpr-923584

ABSTRACT

Objective To investigate the role of tolerogenic dendritic cell (tolDC) in inducing immune tolerance in liver transplantation. Methods Liver transplantation rat models of spontaneous tolerance [Brown Norway (BN)→Lewis, tolerance group, n=6] and acute rejection (AR) (Lewis→BN) were established. In AR rat models, tolDC transfusion was performed in the study group (tolDC group, n=6) and no intervention was given in the control group (AR group, n=6). The survival time of rats in each group was observed. The transplant liver tissues of rats were prepared for pathological examination in each group. The expression of myeloid dendritic cell (mDC) and plasmacytoid dendritic cell (pDC) in rat peripheral blood, transplant liver, spleen and lymph nodes in each group was detected by flow cytometry. The expression levels of serum interleukin (IL)-10 and interferon (IFN)-γ in each group were measured by enzyme-linked immune absorbent assay. Results Pathological manifestations of rats in the AR group mainly included inflammatory cell infiltration and tissue structural disorder in transplant liver, and the survival time was 7-14 d. In the tolDC and tolerance groups, the transplant liver tissues were almost normal, and the longest survival time exceeded 100 d. Compared with the AR group, the expression levels of CD11+mDC in peripheral blood, transplant liver, spleen and lymph nodes of rats were significantly down-regulated in the tolerance and tolDC groups (all P < 0.05), and those of CD86 and major histocompatibility complex (MHC)Ⅱon the surface of CD11+mDC were also significantly down-regulated (all P < 0.05). Compared with the AR group, the expression levels of pDC in peripheral blood, transplant liver, spleen and lymph nodes of rats were significantly up-regulated in the tolerance and tolDC groups (all P < 0.05), whereas those of MHCⅡon the surface of pDC were all significantly down-regulated (all P < 0.05). Compared with the AR group, the expression levels of serum IL-10 were significantly up-regulated, and IFN-γ were significantly down-regulated in the tolerance and tolDC groups (all P < 0.05). Conclusions As tolDC subsets, mDC and pDC play a positive role in regulating the incidence of graft immune tolerance in rats after liver transplantation.

12.
Article in English | WPRIM | ID: wpr-937424

ABSTRACT

Background@#It is well-established that serum testosterone in men decreases with age, yet the underlying mechanism of this change remains elusive. @*Methods@#The expression patterns of Fancd2 opposite-strand (Fancd2os) in BALB/c male mice and testicular tissue derived cell lines (GC-1, GC-2, TM3, and TM4) were assessed using real-time polymerase chain reaction (RT-PCR), Western blot and immunofluorescence. The Fancd2os-overexpressing or knockdown TM3 cells were constructed by infecting them with lentivirus particles and were used to evaluated the function of Fancd2os. The testosterone production was measured using enzyme linked immunosorbent assay (ELISA) and the steroidogenic enzymes such as steroidogenic acute regulatory protein (StAR), P450 cholesterol side-chain cleavage (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD) were analysed using RT-PCR. The apoptosis of TM3 cells induced by ultraviolet light or testicular tissues was detected using flow cytometry, Western blot or dUTP-biotin nick end labeling (TUNEL) assays. Pearson correlation analysis was used to assess the correlation between the Fancd2os expression and TUNEL-positive staining in mouse testicular Leydig cells. @*Results@#The Fancd2os protein was predominantly expressed in mouse testicular Leydig cells and its expression increased with age. Fancd2os overexpression inhibited testosterone levels in TM3 Leydig cells, whereas knockdown of Fancd2os elevated testosterone production. Fancd2os overexpression downregulated the levels of StAR, P450scc and 3β-HSD, while Fancd2os knockdown reversed this effect. Fancd2os overexpression promoted ultraviolet light-induced apoptosis of TM3 cells. In contrast, Fancd2os knockdown restrained apoptosis in TM3 cells. In vivo assays revealed that higher Fancd2os levels and mouse age were associated with increased apoptosis in Leydig cells and decreased serum testosterone levels. Pearson correlation analysis exhibited a strong positive correlation between the expression of Fancd2os and TUNEL-positive staining in mouse testicular Leydig cells. @*Conclusion@#Our findings suggest that Fancd2os regulates testosterone synthesis via both steroidogenic enzymes and the apoptotic pathway.

13.
Acta Pharmaceutica Sinica ; (12): 2269-2282, 2022.
Article in Chinese | WPRIM | ID: wpr-937043

ABSTRACT

Transient receptor potential vanilloid 3 (TRPV3) is a non-selective cation channel, located on cell membranes. TRPV3 is extensively expressed in various organs such as skin, brain, dorsal root ganglia, heart and colon. It's reported that TRPV3 involves in many physiological processes including sensation, skin barrier formation, hair growth and vasodilatation, and pathological processes like pruritus, cutaneous inflammatory disease and cancer. TRPV3 can respond to innoxious warm stimulation (≥ 33 ‍℃‍), endogenous substances (e.‍g., farnesylpyrophosphate) and exogenous small molecules (e.g., carvacrol, camphor and 2-APB). Recently, several natural or synthetic small molecules (e.g., osthole, 74a and dyclonine) have been shown to suppress TRPV3 activity, accompanying with therapeutic efficacy in animal models of diseases, which suggests the potential of TRPV3 as drug target. This paper reviews the research progress on the structure, physiological functions, related diseases and modulators of the TRPV3 channel to provide theoretical references for the future study on TRPV3 channel.

14.
Chinese Journal of School Health ; (12): 1090-1094, 2022.
Article in Chinese | WPRIM | ID: wpr-936545

ABSTRACT

Objective@#To explore the relationship between prepregnancy body mass index, weight gain during pregnancy with preschool obesity and body composition in offspring, so as to provide evidence for gestational weight gain and childhood obesity prevention.@*Methods@#A total of 1 333 preschool children were recruited from 3 kindergartens in Tianjin from September to December 2020. Structured questionnaire was used to collect children s lifestyle information. Height, weight and body fat mass of children were assessed, and body fat percentage (FM%), fat mass index (FMI) and non fat mass index (FFMI) were calculated. Maternal medical records were collected and the mothers were grouped according to their prepregnancy weight status and weight gain during pregnancy. χ 2 test, t test, linear regression model and Logistic regression were used to analyze the differences of obesity and body composition among different groups.@*Results@#The prevalence of overweight and obesity in preschoolers was 12.7% and 7.7%. After adjusting maternal age and delivery, gestational age, gender, age and lifestyle of children, the correlation between maternal pre pregnancy BMI,gestational weight gain with obesity and body composition indexes of children in preschool age was statistically significant ( P <0.05). For mothers with normal weight before pregnancy, excessive weight gain during pregnancy increased risk of high FM% and high FMI in offspring ( OR=1.81, 1.68, P <0.05). There was no significant correlation between maternal weight gain during pregnancy with offspring obesity and body composition among mothers with prepregnant overweight or obesity.@*Conclusion@#Maternal weight status before pregnancy and weight gain during pregnancy are correlated with obesity and body composition in the preschool age of offspring. It is suggested that mothers should maintain appropriate weight status before and during pregnancy.

15.
Article in Chinese | WPRIM | ID: wpr-936142

ABSTRACT

OBJECTIVE@#To explore the incidence of ischemic stroke after the onset of type 2 diabetes, and further analyze the risk factors, so as to provide a basis for further research.@*METHODS@#The data were obtained from the database of the Beijing Urban Employee Basic Medical Insurance Database. The study used a prospective design to describe the incidence of ischemic stroke in patients with type 2 diabetes. In our study, these patients were followed up for seven years. Multivariate Logistic regression models were used to analyze the risk factors of ischemic stroke in patients with type 2 diabetes.@*RESULTS@#A total of 185 813 newly diagnosed type 2 diabetes patients were enrolled, with an average age of (58.5±13.2) years, and 49.0% of them were males. A total of 10 393 patients with newly diagnosed ischemic stroke occurred in 7 years, with a cumulative incidence of 5.6% and an incidence density of 8.1/1 000 person-years. Ischemic stroke occurred in all age groups in patients with type 2 diabetes. The cumulative incidence was 1.5% (95%CI: 1.3%-1.6%) in group ≤44 years old, 3.6% (95%CI: 3.4%-3.7%) in group 45-54 years old, 5.4% (95%CI: 5.2%-5.5%) in group 55-64 years old, and 9.2% (95%CI: 9.0%-9.4%) in group ≥65 years old, and the cumulative incidence increased with age (P < 0.05). Cumulative incidence rate of the males (6.8%, 95%CI: 6.7%-7.0%) was higher than the females (4.4%, 95%CI: 4.3%-4.6%). Among the patients < 80 years old, the cumulative incidence rate of the males was higher than that of the females in all the age groups. In the patients ≥80 years of age, the cumulative incidence was higher in the females (9.2%) than in the males (7.9%). Further analysis revealed that complications, such as coronary heart disease (OR=3.18, 95%CI: 2.72-3.72), heart failure (OR=1.53, 95%CI: 1.32-1.79) and kidney failure (OR=1.45, 95%CI: 1.20-1.75) were associated with ischemic stroke in the patients with type 2 diabetes.@*CONCLUSION@#The incidence level of ischemic stroke in patients with type 2 diabetes is high. It is necessary to strengthen the management of risk factors in elderly patients, screen the complications of type 2 diabetes as early as possible, and take active preventive and control measures.


Subject(s)
Adult , Aged , Aged, 80 and over , Beijing/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Female , Humans , Incidence , Ischemic Stroke , Male , Middle Aged , Prospective Studies , Risk Factors , Stroke/etiology
16.
Frontiers of Medicine ; (4): 111-125, 2022.
Article in English | WPRIM | ID: wpr-929188

ABSTRACT

The Coronavirus disease 2019 (COVID-19) has spread globally. Although mixed liver impairment has been reported in COVID-19 patients, the association of liver injury caused by specific subtype especially chronic hepatitis B (CHB) with COVID-19 has not been elucidated. In this multi-center, retrospective, and observational cohort study, 109 CHB and 327 non-CHB patients with COVID-19 were propensity score matched at an approximate ratio of 3:1 on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, disease severity, and clinical outcomes were compared. Furthermore, univariable and multivariable logistic and Cox regression models were used to explore the risk factors for disease severity and mortality, respectively. A higher proportion of CHB patients (30 of 109 (27.52%)) developed into severe status than non-CHB patients (17 of 327 (5.20%)). In addition to previously reported liver impairment markers, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin, we identified several novel risk factors including elevated lactate dehydrogenase (⩾ 245 U/L, hazard ratio (HR) = 8.639, 95% confidence interval (CI) = 2.528-29.523; P < 0.001) and coagulation-related biomarker D-dimer (⩾ 0.5 µg/mL, HR = 4.321, 95% CI = 1.443-12.939; P = 0.009) and decreased albumin (< 35 g/L, HR = 0.131, 95% CI = 0.048-0.361; P < 0.001) and albumin/globulin ratio (< 1.5, HR = 0.123, 95% CI = 0.017-0.918; P = 0.041). In conclusion, COVID-19 patients with CHB were more likely to develop into severe illness and die. The risk factors that we identified may be helpful for early clinical surveillance of critical progression.


Subject(s)
COVID-19 , Cohort Studies , Hepatitis B, Chronic/epidemiology , Humans , Retrospective Studies , Risk Factors
17.
Article in English | WPRIM | ID: wpr-929058

ABSTRACT

Acetaminophen, also known as N-acetyl-p-aminophenol (APAP), is commonly used as an antipyretic and analgesic agent. APAP overdose can induce hepatic toxicity, known as acetaminophen-induced liver injury (AILI). However, therapeutic doses of APAP can also induce AILI in patients with excessive alcohol intake or who are fasting. Hence, there is a need to understand the potential pathological mechanisms underlying AILI. In this review, we summarize three main mechanisms involved in the pathogenesis of AILI: hepatocyte necrosis, sterile inflammation, and hepatocyte regeneration. The relevant factors are elucidated and discussed. For instance, N-acetyl-p-benzoquinone imine (NAPQI) protein adducts trigger mitochondrial oxidative/nitrosative stress during hepatocyte necrosis, danger-associated molecular patterns (DAMPs) are released to elicit sterile inflammation, and certain growth factors contribute to liver regeneration. Finally, we describe the current potential treatment options for AILI patients and promising novel strategies available to researchers and pharmacists. This review provides a clearer understanding of AILI-related mechanisms to guide drug screening and selection for the clinical treatment of AILI patients in the future.


Subject(s)
Acetaminophen/toxicity , Analgesics, Non-Narcotic/toxicity , Animals , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury, Chronic/pathology , Humans , Inflammation/metabolism , Liver/pathology , Mice , Mice, Inbred C57BL , Necrosis/pathology
18.
Chinese Journal of Burns ; (6): 328-334, 2022.
Article in Chinese | WPRIM | ID: wpr-936014

ABSTRACT

Objective: To explore the clinical effects of free transplantation of expanded thoracodorsal artery perforator flaps in reconstructing cervical cicatrix contracture deformity after burns. Methods: A retrospective observational study was conducted. From May 2018 to April 2021, 11 patients with cervical cicatrix contracture deformity after burns who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University, including 3 males and 8 females, aged 5 to 46 years, with a course of cervical cicatrix contracture deformity of 5 months to 8 years. The degree of cervical cicatrix contracture deformity was degree Ⅰ in one patient, degree Ⅱ in nine patients, and degree Ⅲ in one patient. In the first stage, according to the sizes of neck scars, one rectangular skin and soft tissue expander (hereinafter referred to as expander) with rated capacity of 200 to 600 mL was placed in the back. The expansion time was 4 to 12 months with the total normal saline injection volume being 3.0 to 3.5 times of the rated capacity of expander. In the second stage, free expanded thoracodorsal artery perforator flaps with areas of 10 cm×7 cm to 24 cm×13 cm were cut out to repair the wounds with areas of 9 cm×6 cm to 23 cm×12 cm which was formed after cervical cicatectomy. The main trunk of thoracodorsal artery and vein were selected for end-to-end anastomosis with facial artery and vein, and the donor sites were directly closed. The survival of flaps and healing of flap donor sites were observed on the 14th day post surgery. The appearances and cicatrix contracture deformity of the flaps, recovery of cervical function, and scar hyperplasia of donor sites were followed up. Results: On the 14th day post surgery, the flaps of ten patients survived, while ecchymosis and epidermal necrosis occurred in the center of flap of one patient and healed 2 weeks after dressing change. On the 14th day post surgery, the flap donor sites of 11 patients all healed well. During the follow-up of 6-12 months post surgery, the flaps of ten patients were similar to the skin around the recipient site in texture and color, while the flap of one patient was slightly swollen. All of the 11 patients had good recovery of cervical function and no obvious scar hyperplasia nor contracture in the flaps or at the donor sites. Conclusions: Application of expanded thoracodorsal artery perforator flaps can restore the appearance and function of the neck, and cause little damage to the donor site in reconstructing the cervical cicatrix contracture deformity after burns, which is worthy of clinical reference and application.


Subject(s)
Arteries , Burns/surgery , Cicatrix/surgery , Contracture/surgery , Female , Humans , Hyperplasia , Male , Perforator Flap , Reconstructive Surgical Procedures , Skin Transplantation , Soft Tissue Injuries/surgery , Treatment Outcome
19.
Chinese Journal of Burns ; (6): 266-275, 2022.
Article in Chinese | WPRIM | ID: wpr-936004

ABSTRACT

Objective: To investigate the effects of exosomes from human adipose-derived mesenchymal stem cells (ADSCs) on pulmonary vascular endothelial cells (PMVECs) injury in septic mice and its mechanism. Methods: The experimental research method was adopted. The primary ADSCs were isolated and cultured from the discarded fresh adipose tissue of 3 patients (female, 10-25 years old), who were admitted to the First Affiliated Hospital of Air Force Medical University undergoing abdominal surgery, and the cell morphology was observed by inverted phase contrast microscope on the 5th day. The expressions of CD29, CD34, CD44, CD45, CD73, and CD90 of ADSCs in the third passage were detected by flow cytometry. The third to the fifth passage of ADSCs were collected, and their exosomes from the cell supernatant were obtained by differential ultracentrifugation, and the shape, particle size, and the protein expressions of CD9, CD63, tumor susceptibility gene 101 (TSG101), and β-actin of exosomes were detected, respectively, by transmission electron microscopy, nano-particle tracking analysis and Western blotting. Twenty-four adult male BALB/c mice were adopted and were divided into normal control group, caecal ligation perforation (CLP) alone group, and CLP+ADSC-exosome group with each group of 8 according to random number table (the same grouping method below) and were treated accordingly. At 24 h after operation, tumor necrosis factor (TNF-α) and interleukin 1β (IL-1β) levels of mice serum were detected by enzyme-linked immunosorbent assay, and lung tissue morphology of mice was detected by hematoxylin-eosin and myeloperoxidase staining, and the expression of 8-hydroxy-deoxyguanosine (8-OHdG) of mouse lung cells was detected by immunofluorescence method. Primary PMVECs were obtained from 1-month-old C57 mice regardless gender by tissue block method. The expression of CD31 of PMVECs was detected by immunofluorescence and flow cytometry. The third passage of PMVECs was co-cultured with ADSCs derived exosomes for 12 h, and the phagocytosis of exosomes by PMVECs was detected by PKH26 kit. The third passage of PMVECs were adopted and were divided into blank control group, macrophage supernatant alone group, and macrophage supernatant+ADSC-exosome group, with 3 wells in each group, which were treated accordingly. After 24 h, the content of reactive oxygen species in cells was detected by flow cytometry, the expression of 8-OHdG in cells was detected by immunofluorescence, and Transwell assay was used to determine the permeability of cell monolayer. The number of samples in above were all 3. Data were statistically analyzed with one-way analysis of variance and least significant difference t test. Results: The primary ADSCs were isolated and cultured to day 5, growing densely in a spindle shape with a typical swirl-like. The percentages of CD29, CD44, CD73 and CD90 positive cells of ADSCs in the third passage were all >90%, and the percentages of CD34 and CD45 positive cells were <5%. Exosomes derived from ADSCs of the third to fifth passages showed a typical double-cavity disc-like structure with an average particle size of 103 nm, and the protein expressions of CD9, CD63 and TSG101 of exosomes were positive, while the protein expression of β-actin of exosomes was negative. At 24 h after operation, compared with those in normal control group, both the levels of TNF-α and IL-1β of mice serum in CLP alone group were significantly increased (with t values of 28.76 and 29.69, respectively, P<0.01); compared with those in CLP alone group, both the content of TNF-α and IL-1β of mice serum in CLP+ADSC-exosome group was significantly decreased (with t values of 9.90 and 4.76, respectively, P<0.05 or P<0.01). At 24 h after surgery, the pulmonary tissue structure of mice in normal control group was clear and complete without inflammatory cell infiltration; compared with those in normal control group, the pulmonary tissue edema and inflammatory cell infiltration of mice in CLP alone group were more obvious; compared with those in CLP alone group, the pulmonary tissue edema and inflammatory cell infiltration of mice in CLP+ADSC-exosome group were significantly reduced. At 24 h after operation, endothelial cells in lung tissues of mice in 3 groups showed positive expression of CD31; compared with that in normal control group, the fluorescence intensity of 8-OHdG positive cells of the lung tissues of mice in CLP alone group was significantly increased, and compared with that in CLP alone group, the fluorescence intensity of 8-OHdG positive cells in the lung tissues of mice in CLP+ADSC-exosome group was significantly decreased. The PMVECs in the 3rd passage showed CD31 positive expression by immunofluorescence, and the result of flow cytometry showed that CD31 positive cells accounted for 99.5%. At 12 h after co-culture, ADSC-derived exosomes were successfully phagocytose by PMVECs and entered its cytoplasm. At 12 h after culture of the third passage of PMVECs, compared with that in blank control group, the fluorescence intensity of reactive oxygen species of PMVECs in macrophage supernatant alone group was significantly increased (t=15.73, P<0.01); compared with that in macrophage supernatant alone group, the fluorescence intensity of reactive oxygen species of PMVECs in macrophage supernatant+ADSC-exosome group was significantly decreased (t=4.72, P<0.01). At 12 h after culture of the third passage of PMVECs, and the 8-OHdG positive fluorescence intensity of PMVECs in macrophage supernatant alone group was significantly increased; and compared with that in blank control group, the 8-OHdG positive fluorescence intensity of PMVECs in macrophage+ADSC-exosome supernatant group was between blank control group and macrophage supernatant alone group. At 12 h after culture of the third passage PMVECs, compared with that in blank control group, the permeability of PMVECs monolayer in macrophage supernatant alone group was significantly increased (t=6.34, P<0.01); compared with that in macrophage supernatant alone group, the permeability of PMVECs monolayer cells in macrophage supernatant+ADSC-exosome group was significantly decreased (t=2.93, P<0.05). Conclusions: Exosomes derived from ADSCs can ameliorate oxidative damage in mouse lung tissue, decrease the level of reactive oxygen species, 8-OHdG expression, and permeability of PMVECs induced by macrophage supernatant.


Subject(s)
Animals , Endothelial Cells/metabolism , Exosomes/metabolism , Female , Humans , Lung Injury/metabolism , Male , Mesenchymal Stem Cells/metabolism , Mice , Sepsis/pathology
20.
Chinese Journal of Hepatology ; (12): 38-44, 2022.
Article in Chinese | WPRIM | ID: wpr-935906

ABSTRACT

Objective: To investigate the effect of adenovirus-mediated shRNA down-regulating phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression on vinculin, filamin A, and cortactin in activated hepatic stellate cells (HSCs). Methods: Activated rats hepatic stellate cell line (HSC-T6) was cultured in vitro. Recombinant adenovirus Ad-shRNA/PTEN carrying PTEN targeted RNA interference sequence [short hairpin RNA (shRNA)] and empty control virus Ad-GFP were transfected into HSCs. The PTEN mRNA and protein expression of HSCs in each group were detected by real-time fluorescence quantitative PCR and Western blot. The expressional change of vinculin, filamin A and cortactin in HSCs of each group were detected by confocal laser scanning immunofluorescence microscope. Image-pro plus 6.0 software was used for image analysis and processing. The integrated optical density (IOD) of the fluorescence protein expression was measured. The experiment was divided into three groups: control group (DMEM instead of adenovirus solution in the adenovirus transfection step), Ad-GFP group (transfected with empty virus Ad-GFP only expressing green fluorescent protein), and Ad-shRNA/PTEN group (recombinant adenovirus Ad-shRNA/PTEN carrying shRNA targeting PTEN and expressing green fluorescent protein). One-way analysis of variance was used for comparison of mean value among the three groups, and LSD-test was used for comparison between the groups. Results: shRNA targeted PTEN was successfully transfected and the expression of PTEN mRNA and protein in HSC (P < 0.05) was significantly down-regulated. HSCs vinculin was mainly expressed in the cytoplasm. HSCs vinculin fluorescence IOD in the Ad-shRNA/PTEN group (19 758.83 ± 1 520.60) was higher than control (7 737.16 ± 279.93) and Ad-GFP group (7 725.50 ± 373.03) (P < 0.05), but there was no statistically significant difference between control group and Ad-GFP group (P > 0.05). There was no statistically significant difference in the fluorescence IOD of Filamin A among the three groups (P > 0.05), but the subcellular distribution of Filamin A among the three groups were changed. Filamin A in the Ad-shrNA /PTEN HSC group was mainly distributed in the cytoplasm. Filamin A HSC was mainly located in the nucleus.The filamin A HSC in the control group and Ad-GFP group was mainly located in the nucleus. The nucleocytoplasmic ratio of Filamin A in the AD-shrNA /PTEN group (0.60 ± 0.15) was significantly lower than control group (1.20 ± 0.15) and Ad-GFP group (1.08 ± 0.23), P < 0.05. but there was no statistically significant difference in filamin A nucleocytoplasmic ratio of HSC between the control group and the Ad-GFP group (P > 0.05). Cortactin HSCs in the three groups was mainly distributed in the cytoplasm. The cortactin fluorescence IOD of HSCs in the Ad-shRNA/PTEN group was significantly higher than control group (22 959.94 ± 1 710.42) and the Ad-GFP group (22 547.11 ± 1 588.72 ) (P < 0.05), while there was no statistically significant difference in the IOD of cortactin fluorescence in HSCs between the control group and the Ad-GFP group (P > 0.05). Conclusion: The down-regulation of PTEN expression raises the expression of microfilament-binding protein vinculin and cortactin, and changes the subcellular distribution of another microfilament binding protein filamin A, that is, translocation from nucleus to the cytoplasm in activated HSC in vitro.


Subject(s)
Adenoviridae/metabolism , Animals , Carrier Proteins , Cell Proliferation , Cortactin , Filamins/genetics , Hepatic Stellate Cells/metabolism , PTEN Phosphohydrolase/metabolism , RNA, Small Interfering/genetics , Rats , Vinculin/genetics
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