Obesity is a worldwide health problem. An imbalance in energy metabolism is an important cause of obesity and related metabolic diseases. Our previous studies showed that inhibition of miR-429 increased the protein level of uncoupling protein 1 (UCP1) in beige adipocytes; however, whether local inhibition of miR-429 in subcutaneous adipose tissue affects diet-induced obesity and related metabolic disorders remains unclear. The aim of this study was to investigate the effect of local overexpression of miR-429 sponge in subcutaneous adipose tissue on obesity and related metabolic disorders. The control adeno-associated virus (AAV) or AAV expressing the miR-429 sponge was injected into mouse inguinal white adipose tissue. Seven days later, the mice were fed a high-fat diet for 10 weeks to induce obesity. The effects of the miR-429 sponge on body weight, adipose tissue weight, plasma glucose and lipid levels, and hepatic lipid content were explored. The results showed that the overexpression of miR-429 sponge in subcutaneous white adipose tissue reduced body weight and fat mass, decreased fasting blood glucose and plasma cholesterol levels, improved glucose tolerance, and alleviated hepatic lipid deposition in mice. Mechanistic investigation showed that the inhibition of miR-429 significantly upregulated the expression of UCP1 in adipocytes and adipose tissue. These results suggest that local inhibition of miR-429 in subcutaneous white adipose tissue ameliorates obesity and related metabolic disorders potentially by upregulating UCP1, and miR-429 is a potential therapeutic target for the treatment of obesity and related metabolic disorders.
Animals ; MicroRNAs/physiology* ; Obesity/metabolism* ; Mice ; Adipose Tissue, White/metabolism* ; Metabolic Diseases ; Subcutaneous Fat/metabolism* ; Male ; Uncoupling Protein 1/metabolism* ; Diet, High-Fat ; Mice, Inbred C57BL

ObjectiveThe absorption of substances into blood is mainly dependent on the mesenteric lymphatic pathway and the portal venous pathway. The substances transported via the portal venous pathway can be metabolized by the biotransformation in the liver. On the contrary, the substances in the mesenteric lymph fluid enter the blood circulation without biotransformation and can affect the body directly. Alcohol consumption is strongly linked to global health risk. Previous reports have analyzed the changes of metabolites in plasma, serum, urine, liver and feces after alcohol consumption. Whether alcohol consumption affects the metabolites in lymph fluid is still unknown. Therefore, it is particularly important to explore the changes of substances transported via the mesenteric lymphatic pathway and analyze their harmfulness after alcohol drinking. MethodsIn this study, male Wistar rats were divided into high, medium, and low-dosage alcohol groups (receiving Chinese Baijiu at 56%, 28% and 5.6% ABV, respectively) and water groups. The experiment was conducted by alcohol gavage lasting 10 d, 10 ml·kg^-1·d^-1. Then mesenteric lymph fluid was collected for non-targeted metabolomic analysis by using liquid chromatography-mass spectrometry (LC-MS) and bioinformatic analysis. Principal component analysis and hierarchical clustering were performed by using Biodeep. Meanwhile, KEGG enrichment analysis of the differential metabolites was also performed by Biodeep. MetaboAnalyst was used to analyze the relationship between the differential metabolites and diseases. ResultsThe metabolites in the mesenteric lymph fluid of the high-dosage alcohol group change the most. Based on the KEGG enrichment analysis, the pathways of differential metabolites between the high-dosage alcohol group and the control group are mainly enriched in the central carbon metabolism in cancer, bile secretion, linoleic acid metabolism, biosynthesis of unsaturated fatty acids, etc. Interestingly, in the biosynthesis of unsaturated fatty acids category, the content of arachidonic acid is increased by 7.25 times, whereas the contents of palmitic acid, oleic acid, stearic acid, arachidic acid and erucic acid all decrease, indicating lipid substances in lymph fluid are absorbed selectively after alcohol intake. It’s worth noting that arachidonic acid is closely related to inflammatory response. Furthermore, the differential metabolites are mainly related with schizophrenia, Alzheimer’s disease and lung cancer. The differential metabolites between the medium-dosage alcohol and the control group were mainly enriched in phenylalanine metabolism, valine, leucine and isoleucine biosynthesis, linoleic acid metabolism and cholesterol metabolism. The differential metabolites are mainly related to schizophrenia, Alzheimer’s disease, lung cancer and Parkinson’s disease. As the dose of alcohol increases, the contents of some metabolites in lymph fluid increase, including cholesterol, L-leucine, fumaric acid and mannitol, and the number of metabolites related to schizophrenia also tends to increase, indicatingthat some metabolites absorbed by the intestine-lymphatic pathway are dose-dependent on alcohol intake. ConclusionAfter alcohol intake, the metabolites transported via the intestinal-lymphatic pathway are significantly changed, especially in the high-dosage group. Some metabolites absorbed via the intestinal-lymphatic pathway are dose-dependent on alcohol intake. Most importantly, alcohol intake may cause inflammatory response and the occurrence of neurological diseases, psychiatric diseases and cancer diseases. High-dosage drinking may aggravate or accelerate the occurrence of related diseases. These results provide new insights into the pathogenesis of alcohol-related diseases based on the intestinal-lymphatic pathway.

Increased neuronal apoptosis is an important pathological feature of Alzheimer's disease (AD). The Bcl-2-interacting mediator of cell death (Bim) mediates amyloid-beta (Aβ)-induced neuronal apoptosis. Naturally-occurring antibodies against Bim (NAbs-Bim) exist in human blood, with their levels and functions unknown in AD. In this study, we found that circulating NAbs-Bim were decreased in AD patients. Plasma levels of NAbs-Bim were negatively associated with brain amyloid burden and positively associated with cognitive functions. Furthermore, NAbs-Bim purified from intravenous immunoglobulin rescued the behavioral deficits and ameliorated Aβ deposition, tau hyperphosphorylation, microgliosis, and neuronal apoptosis in APP/PS1 mice. In vitro investigations demonstrated that NAbs-Bim were neuroprotective against AD through neutralizing Bim-directed neuronal apoptosis and the amyloidogenic processing of amyloid precursor protein. These findings indicate that the decrease of NAbs-Bim might contribute to the pathogenesis of AD and immunotherapies targeting Bim hold promise for the treatment of AD.
Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Animals ; Disease Models, Animal ; Humans ; Mice ; Mice, Transgenic

Objective: To understand the prevalence of chronic kidney disease (CKD) and related factors in adults in Anhui province based on the data of Chinese Chronic Diseases and Nutrition Surveillance program (2018) in Anhui. Methods: Multi-stage stratified cluster random sampling was used to select participants aged ≥18 years. Moreover, questionnaire survey, body measurements and laboratory tests were conducted. The complex weighting method was used to estimate the prevalence of CKD in residents with different characteristics, and complex sampling data logistic regression model was used for multivariate analysis to identify related risk factors. Results: A total of 7 181 participants were included. The overall prevalence of CKD was 11.06% in adults in Anhui, and the prevalence was 12.49% in women and 9.59% in men (P<0.05). The moderate, high and very high risk for CKD progression were 8.66%, 2.02% and 0.38%, respectively. Multivariate analysis showed that age (OR=1.03, 95%CI: 1.00-1.05), BMI (OR=1.05, 95%CI: 1.01-1.09), being woman (OR=1.38,95%CI: 1.22-1.55), hypertension (OR=2.50, 95%CI: 1.76-3.56), diabetes (OR=2.28, 95%CI: 1.51-3.43), dyslipidemia (OR=1.26, 95%CI: 1.11-1.43) and hyperuricemia (OR=2.16, 95%CI: 1.68-2.78) were risk factors for CKD. Conclusion: The prevalence of CKD in adults in Anhui was relatively high and age, gender, BMI, hypertension, diabetes, dyslipidemia and hyperuricemia were found to be associated with the prevalence of CKD. To prevent CKD and its complications, attention should be paid to the management of related risk factors, including overweight and obesity, hypertension, diabetes, dyslipidemia and hyperuricemia.
Adult ; Male ; Female ; Humans ; Adolescent ; Cross-Sectional Studies ; Prevalence ; Hyperuricemia/epidemiology* ; Renal Insufficiency, Chronic/epidemiology* ; Hypertension/epidemiology*

Objective:To investigate the possible mechanism of Xieheyin in alleviating obese polycystic ovary syndrome with insulin resistance（PCOS-IR）and reducing inflammatory response. Method:Ten of sixty SPF femlae C57BL/6J mice were randomly selected as the normal group，and the rest mice were given letrozole 0.002 g·kg^-1 combined with fecal suspension 2 g·kg^-1 for 28 consecutive days to establish model of PCOS-IR.The mice that were successfully modeled were randomized into the model group，metformin group（0.25 g·kg^-1），and low（10 g·kg^-1），medium（20 g·kg^-1），and high-dose（40 g·kg^-1）Xieheyin groups，and administered with the corresponding drugs by gavage，once a day，for four consecutive weeks. Except the normal control group， the mice in the other groups were continuously given fecal suspension combined with letrozole solution to maintain the model during the treatment. The mice were weighed once a week.Levels of fasting blood glucose （FBG） were detected by blood glucose test strips.And enzyme-linked immunosorbent assay （ELISA） method was used to detect serum testosterone（T），follicle stimulating hormone（FSH），luteinizing hormone（LH），fasting insulin（FINS）level，and LH/FSH and Homeostasis model assesment of insulin resistance （HOMA-IR） were calculated．The uterus and ovaries were weighed and fixed.Hematoxylin-eosin（HE）staining was used to observe ovarian tissue pathology morphology. Western blot was used to detect the expression levels of tight junction key molecular zonula occludens 1（ZO-1），occludin in colon tissues，and the expression levels of Toll-like receptor 4/nuclear factor kappa B/Nod-like receptor protein 3（TLR4/NF-κB/NLRP3）signaling pathway and inflammation associated proteins cysteinyl aspartate specific proteinase-1（Caspase-1） and interleukin-1β（IL-1β） in colon tissues. Result:Compared with normal control group，the body weight of mice in the model control group increased significantly（P<0.01）. Serum FINS，FBG，HOMA-IR，T，LH/FSH were significantly increased（P<0.05，P<0.01）. The uterine organ ratio were decreased significantly（P<0.01），while the ovarian organ ratio were significantly increased（P<0.01）. The number of atresia follicles and cystic dilatation follicles increased significantly，and the number of corpus luteum significantly decreased，the thickness of follicular granulosa cells also decreased，while the white membrane thickness of the ovary increased. Tight junction related ZO-1，occludin proteins in colon tissues were all decreased（P<0.01）.The relative expression levels of inflammation-related protein IL-1β，Caspase-1 and TLR4/NF-κB/NLRP3 target protein signaling pathway were significantly increased（P<0.05）.Compared with model control group， the body weight of mice in the low，middle and high dose Xieheyin group decreased significantly（P<0.01）. The serum T，LH/FSH，FINS，FBG，HOMA-IR were significantly decreased（P<0.05，P<0.01）. The uterine organ ratio were increased（P<0.05），while the ovarian organ ratio were decreased（P<0.05）. The number of cystic follicles decreased and corpus luteum increased，the thickness of follicular granulosa cells increased and be arranged normally，while the white membrane thickness of the ovary increased slightly. The expressions of ZO-1，occludin proteins were increased（P<0.01）. The expression levels of IL-1β，Caspase-1 and TLR4/NF-κB/NLRP3 target protein in the high dose group were significantly decreased（P<0.01）. Conclusion:Xieheyin could activate intestinal TLR4/NF-κB/NLRP3 signaling pathway，inhibit pro-inflammatory factor secretion，improve obesity and IR，which was correlated with rebuilding intestinal mucosal barrier and inhibiting intestinal inflammation．

OBJECTIVE: To analyse the clinical and laboratory characteristics of antinuclear antibody (ANA) positive rheumatoid arthritis (RA) patients. METHODS: The clinical and laboratory data of 428 RA cases from Department of of Rheumatology and Immunology Peking University Third Hospital from Jan 2013 to Dec 2018 were collected and used to analyse characters between ANA positive group and ANA negative group. T test was used for the quantitative data in accordance with normal distribution. Wilcoxon rank sum test was used for the quantitative data of non normal distribution. The qualitative data were analyzed by chi square test. But while 1≤theoretical frequency < 5, chi square test of corrected four grid table was used. And Fisher exact probability method was used when theoretical frequency < 1. RESULTS: The number of ANA positive group was 231 (54%). The female rate was obviously higher in ANA positive group (82.7% vs. 63.5%, χ²=20.355, P < 0.01). The rate of metatarsophalangeal joints (MTPJs) involvement was lower in ANA positive group (22.1%) than in ANA negative group (33.0) (χ²=6.414, P < 0.05). The incidence of secondary Sjögren's syndrome (sSS) was much higher in ANA positive group(19.5% vs. 4.1%, χ²=23.300, P < 0.01). The positivity of rheumatoid factor (RF), as well as the positivity of anti-cyclic citrullinated peptide(CCP) antibody was much higher in ANA positive group (77.1% vs. 53.8%, χ²=25.743, P < 0.01, 74.9% vs. 59.4%, χ²=11.694, P < 0.01, respectively). The levels of immunoglobulin G (IgG) and immunoglobulin M (IgM) of ANA positive group were higher [(15.1±5.1) g/L vs. (13.8±5.3) g/L, t=2.359, P < 0.05, 1.25 (0.92) g/L vs. 1.05 (0.65) g/L, Z=-3.449, P < 0.01, respectively]. But the levels of hemoglobin (Hb) and platelet (PLT) was lower in ANA positive group[(109.64±17.98) vs. (114.47±18.48) g/L, t=-2.734, P < 0.01; (266.4×10⁹±104.6×10⁹) vs. (295.9×10⁹±100.1×10⁹) /L, t=-2.970, P < 0.01, respectively]. CONCLUSION The incidence of sSS was obviously higher in ANA positive group than in ANA negative group. Serum IgG of ANA positive group was higher, but Hb and PLT were lower.
Antibodies, Antinuclear ; Arthritis, Rheumatoid/epidemiology* ; Autoantibodies ; Female ; Humans ; Laboratories ; Peptides, Cyclic ; Rheumatoid Factor

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01). CONCLUSIONS Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.
Anti-Bacterial Agents ; Birth Weight ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; Surveys and Questionnaires

OBJECTIVE: To investigate the clinical importance of combined detection of urinary amino acid metabolite --urinary tyrosine (UT) and tumor specific growth factor (TSGF) in the disease observation and curative effect evaluation of acute leukemia（AL）. METHODS: In 87 cases of AL, the UT and TSGF levels were detected by using chemical chromogenic method and continuous monitoring method respectively. The 2 indicators of each treatment group were statistically analyzed and compared with that of 50 healthy control group. RESULTS: In 87 AL patients, the levels of UT and TSGF after treatment were significantly lower than those before treatment (P<0.01). The level of UT in non-remission(NR) group and partial remission(PR) group was significantly higher than that in completely remission(CR) group(P<0.01，P<0.05) and control group (P<0.01, P<0.01), The UT level in NR group was significantly higher than that in PR group (P<0.05), the UT level in CR group was significantly higher than that in control group (P<0.05). The levels of TSGF in NR and PR groups were significantly higher than those in CR and control groups(P<0.01, P<0.01). The level of TSGF in NR group was significantly higher than that in PR group(P<0.05), but no significant difference existed between CR group and control group(P>0.05). CONCLUSION UT and TSGF levels are related with the metabolism of tumor cells in AL patients. UT level can be used to predict the recurrence of patients with CR. The combined dynamical monitoring of these 2 indicators can be used as the indexes for observation of AL status, evaluation of therapeutic efficacy, prediction of prognosis and relapse of AL.
Acute Disease ; Amino Acids ; Antigens, Neoplasm ; Humans ; Leukemia, Myeloid, Acute ; Neoplasm Proteins ; Prognosis ; Recurrence

OBJECTIVETo study the effects of ultrasound guided inter-scalene brachial plexus block and patient-controlled infraclavicular brachial plexus block for postoperative pain and surgical efficacy in patients with terrible tyriad of the elbow.

METHODSFrom March 2015 to August 2016, 60 patients with terrible tyriad of the elbows were treated in Ningbo No.6 Hospital with ASA I to II internal fixation. There were 32 males and 28 females, ranging in age from 16 to 70 years old, with a mean age of (55.6±18.2) years old. All the patients were divided into two groups(30 cases in each group): controlled intermuscular groove brachial plexus block (group C), infraclavicular brachial plexus block(group I). All catheters were placed using ultra-sound visualization and injected 0.33% ropivacaine 30 ml preoperatively. After regaining consciousness, all patients connected the electronic pump. The solution contained 0.2% ropiva-caine and the pump was setup to deliver a 5 ml bolus dose, with a 15 min lock out interval and background infusion at 5 ml/h. Both analgesia lasted until 5 d after operation. The patients underwent rehabilitation exercise everyday for 5 consecutive days starting from 24 h after operation.VAS score was recorded at 24 h, 48 h, 72 h and 4 d, 5 d after operation during rest and rehabilitation exercise time. The elbow articular range of motion and Mayo elbow performance score (MEPS) were recorded at 6 d after operation. Catheter-related adversereactions (such as oozing from the insertion site, obstruction, prolapse) were recorded.

RESULTSThe success rate of blockade was 100% during insertion in both groups. Compared with group C, the VAS score at 3 d during rest time and 3, 4, 5 d after operation during rehabili-tation exercise were decreased(2.5±0.5 vs. 3.8±1.1, 3.0±0.4 vs. 5.0±0.9, 2.5±0.4 vs. 4.5±1.2, 2.1±0.3 vs. 4.1±1.0,<0.05). The elbow articular range of motion and MEPS were increased(-2.19±18.01)° vs.(-8.19±12.16)°, (45.15±11.20)° vs. (22.15±7.02)°, (19.06±6.75)° vs. (9.10±2.48)°, (17.08±5.18)° vs. (10.12±3.15)°, (80.80±9.50) points vs. (64.90±11.21) points. The incidence of insertion site, obstruction, prolapse was 15, 5 and 10 cases respectively in group C, but without any catheter-related adverse reactions happened in group I (<0.05).

CONCLUSIONSPatient-controlled infraclavieular brachial plexus block can be effectively used for postoperative pain after fixation for terrible tyriad of the elbows, and it can increase surgical outcome.

Objective To evaluate cardio -pulmonary function and serum interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α( TNF-α) levels for chronic pulmonary heart disease treated by levocarnitine combined with Shenmai injection and study its mecha-nism.Methods A total of 110 patients with chronic pulmonary heart disease were randomly divided into treatment group ( n=55 ) and control group(n=55).Patients in two groups were treated by oxygen , relieving cough and asthma , cardio tonic , diuresis and expand blood.Patients in control group were given levocarnitine 3 g for 3 weeks , while patients in treatment group given Shenmai injection 100 mL for 3 weeks on the basis of control group.The cardio-pulmonary function improvement , changes of serum IL-6, IL-8, TNF-αlevels and incidence of adverse drug reactions were observed between the two groups.Results The improve-ment of forced expiratory volume in one second ( FEV1 ) , forced vital ca-pacity ( FVC ) , FEV1/FVC, and pulmonary artery pressure ( PAP ) in treatment group were significantly better than those in control group after treatment ( P <0.01 ).E peak and Ve after treatment in two groups were significantly higher than those before treatment.A peak and Va after treatment in two groups were significantly lower than those before treatment , and the changes in treatment group was more significant ( P <0.05 ).The serum IL-6,IL-8,TNF-αlevels after treatment were significantly lower than before treatment , and the decline in treatment group was more obvious than control group ( P<0.05).Conclusion Levocarnitine combined with Shenmai injection could significantly improve the cardio -pulmonary function for chronic pulmonary heart disease , reduce PAP, serum IL-6,IL-8,TNF-αlevels and suppress the inflammatory reaction.