OBJECTIVE: To observe the effect of Guilu Taohong Formula on semen quality in varicocele (VC) models of rats, and to explore its possible mechanism. METHODS: Forty-eight male SD rats were randomly divided into four groups (sham group, model group, Guilu Taohong Formula group and L-carnitine group). After the establishment of models, the rats were treated with intragastric administration for eight consecutive weeks. The general condition of the rats was observed. After the gavage, the testicular and epididymal indices were calculated. Semen quality was assessed using an automatic semen analyzer. Apoptosis of testicular cells was assessed by TUNEL staining. And the expression levels of B-cell lymphocytoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and cysteine aspartate protease-3 (caspase-3) in testicular tissue were detected by Western blot. RESULTS: Compared with the sham group, testicular index, epididymal index, sperm concentration, the percentage of progressive motility of sperm (PR%) and the expression level of Bcl-2 decreased in model group(P<0.01). An increased apoptosis rate of spermatogenic cells and the expression levels of Bax and caspase-3 proteins were observed in model group as well(P<0.01). Compared with the model group, the testicular index, epididymal index, sperm concentration, PR% and the expression level of Bcl-2 in Guilu Taohong Formula group increased significantly (P<0.05, P<0.01). A decreased apoptosis rate of spermatogenic cells and the expression levels of Bax and caspase-3 proteins were detected in Guilu Taohong Formula group as well(P<0.01). Similarly, the L-carnitine group showed increased testicular index, epididymal index, sperm concentration, PR% and the expression level of Bcl-2 protein (P<0.05, P<0.01), where showed decreased apoptosis rate of spermatogenic cells and the expression levels of Bax and caspase-3 proteins compared with model group (P<0.01, P<0.05). CONCLUSION Guilu Taohong Formula improves semen quality in VC model rats and reduces the apoptosis rate of spermatogenic cells in testicular tissue, which may be related to the promotion of Bcl-2 protein expression and the inhibition of Bax and caspase-3 protein expression levels.
Male ; Animals ; Varicocele/drug therapy* ; Rats ; Apoptosis/drug effects* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/therapeutic use* ; Semen Analysis ; bcl-2-Associated X Protein/metabolism* ; Caspase 3/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Disease Models, Animal ; Spermatozoa/drug effects* ; Testis/drug effects*

Objective This study investigated the impact of occupational mercury(Hg)exposure on human gene transcription and expression,and its potential biological mechanisms. Methods Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation.Hg-exposed cell models and PTEN low-expression models were established in vitro using 293T cells.PTEN gene expression was assessed using qRT-PCR,and Western blotting was used to measure PTEN,AKT,and PI3K protein levels.IL-6 expression was determined by ELISA. Results Combined findings from gene expression microarray analysis,bioinformatics,and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group.In the Hg-exposed cell model(25 and 10 μmol/L),a significant decrease in PTEN expression was observed,accompanied by a significant increase in PI3K,AKT,and IL-6 expression.Similarly,a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K,AKT,and IL-6 levels. Conclusion This is the first study to report that Hg exposure downregulates the PTEN gene,activates the PI3K/AKT regulatory pathway,and increases the expression of inflammatory factors,ultimately resulting in kidney inflammation.

Objective: To analyze the short-term effect of individual atmospheric PM_2.5 exposure on the diversity, enterotype, and community structure of gut microbiome in healthy elderly people in Jinan, Shandong province. Methods: The present panel study recruited 76 healthy elderly people aged 60-69 years old in Dianliu Street, Lixia District, Jinan, Shandong Province, and followed them up five times from September 2018 to January 2019. The relevant information was collected by questionnaire, physical examination, precise monitoring of individual PM_2.5 exposure, fecal sample collection and gut microbiome 16S rDNA sequencing. The Dirichlet multinomial mixtures (DMM) model was used to analyze the enterotype. Linear mixed effect model and generalized linear mixed effect model were used to analyze the effect of PM_2.5 exposure on gut microbiome α diversity indices (Shannon, Simpson, Chao1, and ACE indices), enterotype and abundance of core species. Results: Each of the 76 subjects participated in at least two follow-up visits, resulting in a total of 352 person-visits. The age of 76 subjects was (65.0±2.8) years old with BMI (25.0±2.4) kg/m². There were 38 males accounting for 50% of the subjects. People with an educational level of primary school or below accounted for 10.5% of the 76 subjects, and those with secondary school and junior college or above accounting for 71.1% and 18.4%. The individual PM_2.5 exposure concentration of 76 subjects during the study period was (58.7±53.7) μg/m³. DMM model showed that the subjects could be divided into four enterotypes, which were mainly driven by Bacteroides, Faecalibacterium, Lachnospiraceae, Prevotellaceae, and Ruminococcaceae. Linear mixed effects model showed that different lag periods of PM_2.5 exposure were significantly associated with a lower gut α diversity index (FDR<0.05 after correction). Further analysis showed that PM_2.5 exposure was significantly associated with changes in the abundances of Firmicutes (Megamonas, Blautia, Streptococcus, etc.) and Bacteroidetes (Alistipes) (FDR<0.05 after correction). Conclusion: Short-term PM_2.5 exposure is significantly associated with a decrease in gut microbiome diversity and changes in the abundance of several species of Firmicutes and Bacteroidetes in the elderly. It is necessary to further explore the underlying mechanisms between PM_2.5 exposure and the gut microbiome, so as to provide a scientific basis for promoting the intestinal health of the elderly.
Aged ; Humans ; Male ; Middle Aged ; Feces/microbiology* ; Gastrointestinal Microbiome ; Particulate Matter ; RNA, Ribosomal, 16S/genetics* ; Female

Emodin nanostructured lipid carriers(ED-NLC) were prepared and their quality was evaluated in vitro. Based on the results of single-factor experiments, the ED-NLC formulation was optimized by Box-Behnken response surface method with the dosages of emodin, isopropyl myristate and poloxamer 188 as factors and the nanoparticle size, encapsulation efficiency and drug loading as evaluation indexes. Then the evaluation was performed on the morphology, size and in vitro release of the nanoparticles prepared by emulsification-ultrasonic dispersion method in line with the optimal formulation, i.e., 3.27 mg emodin, 148.68 mg isopropyl myristate and 173.48 mg poloxamer 188. Under a transmission electron microscope(TEM), ED-NLC were spherical and their particle size distribution was uniform. The particle size of ED-NLC was(97.02±1.55) nm, the polymer dispersion index 0.21±0.01, the zeta potential(-38.96±0.65) mV, the encapsulation efficiency 90.41%±0.56% and the drug loading 1.55%±0.01%. The results of differential scanning calorimeter(DSC) indicated that emodin may be encapsulated into the nanostructured lipid carriers in molecular or amorphous form. In vitro drug release had obvious characteristics of slow release, which accorded with the first-order drug release equation. The fitting model of Box-Behnken response surface methodology was proved accurate and reliable. The optimal formulation-based ED-NLC featured concentrated particle size distribution and high encapsulation efficiency, which laid a foundation for the follow-up study of ED-NLC in vivo.
Drug Carriers ; Emodin ; Follow-Up Studies ; Lipids ; Nanostructures

Objective: To determine the impact of inflammatory reaction levels and the culprit plaque characteristics on preprocedural Thrombolysis in Myocardial Infarction (TIMI) flow grade in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: The is a retrospective study. A total of 1 268 STEMI patients who underwent pre-intervention optical coherence tomography (OCT) examination of culprit lesion during emergency PCI were divided into 2 groups by preprocedural TIMI flow grade (TIMI 0-1 group (n =964, 76.0%) and TIMI 2-3 group (n =304, 24.0%)). Baseline clinical data of the 2 groups were collected; blood samples were collected for the detection of inflammatory markers such as high sensitivity C-reactive protein (hsCRP), myocardial injury marker, blood lipid, etc.; echocardiography was used to determine left ventricular ejection fraction; coronary angiography and OCT were performed to define the lesion length, diameter stenosis degree of the infarct-related arteries, presence or absence of complex lesions, culprit lesion type, area stenosis degree and vulnerability of culprit plaques. Multivariable logistic regression analysis was performed to identify independent correlation factors. The receiver operating characteristic (ROC) curve of continuous independent correlation factors was analyzed, and the best cut-off value of TIMI 0-1 was respectively determined according to the maximum value of Youden index. Results: The mean age of 1 268 STEMI patients were (57.6±11.4) years old and 923 cases were males (72.8%). Compared with TIMI 2-3 group, the patients in TIMI 0-1 group were older and had higher N-terminal-pro-B-type natriuretic peptide level, lower cardiac troponin I (cTnI) level, lower left ventricular ejection fraction, and higher hsCRP level (5.16(2.06, 11.78) mg/L vs. 3.73(1.51, 10.46) mg/L). Moreover, the hsCRP level of patients in TIMI 0-1 group was higher in the plaque rupture subgroup (all P<0.05). Coronary angiography results showed that compared with TIMI 2-3 group, the proportion of right coronary artery (RCA) as the infarct-related artery was higher, the angiographical lesion length was longer, minimal lumen diameter was smaller, and diameter stenosis was larger in TIMI 0-1 group (all P<0.05). The prevalence of plaque rupture was higher (75.8% vs. 61.2%) in TIMI 0-1 group. Plaque vulnerability was significantly higher in TIMI 0-1 group than that in TIMI 2-3 group with larger mean lipid arc (241.27°±46.78° vs. 228.30°±46.32°), more thin-cap fibroatheroma (TCFA, 72.4% vs. 57.9%), more frequent appearance of macrophage accumulation (84.4% vs. 70.7%) and cholesterol crystals (39.1% vs. 25.7%). Minimal flow area was smaller [1.3(1.1-1.7)mm² vs. 1.4(1.1-1.9)mm², all P<0.05] and flow area stenosis was higher (78.2%±10.6% vs. 76.3%±12.3%) in TIMI 0-1 group. Multivariable analysis showed that mean lipid arc>255.55°, cholesterol crystals, angiographical lesion length>16.14 mm, and hsCRP>3.29 mg/L were the independent correlation factors of reduced preprocedural TIMI flow grade in STEMI patients. Conclusions: Plaque vulnerability and inflammation are closely related to reduced preprocedural TIMI flow grade in STEMI patients.
Aged ; Coronary Angiography ; Humans ; Inflammation ; Male ; Middle Aged ; Myocardial Infarction/diagnostic imaging* ; Percutaneous Coronary Intervention ; Plaque, Atherosclerotic/diagnostic imaging* ; Retrospective Studies ; ST Elevation Myocardial Infarction/surgery* ; Stroke Volume ; Thrombolytic Therapy ; Ventricular Function, Left

In order to analyze the temporal distribution characteristics of human rabies in China and explore the incidence forecasting,R3.3.2 software were used to establish the optimal ARIMA model of monthly incidences from 2004 to 2015 in Chi-na.Then the monthly incidences from January to November 2016 were forecasted with the model and the prediction accuracy was evaluated.The annual incidences of human rabies in China were decreasing tendency since 2007,and the monthly incidence reached highly during August to October.The optimal model was ARIMA(2,1,1)(2,0,0)12and the mean absolute error (MASE)was 0.755.The mean relative error was 15.61% when predicting the incidences from January to November 2016.In conclusion,there exists seasonal variation for human rabies in China and ARIMA model can be applied for the short-term fore-casting.

Objective To investigate the relationship between exon 11 CAG triplet nucleotide repeats ([CAG]n) of myocyte enhancer binding factor-2A (MEF2A ) polymorphisms and ischemic stroke caused by large artery atherosclerosis (LAA). Methods Two hundred and five patients with first onset ischemic stroke caused by LAA, admitted to our hospital from June 2010 to December 2014, and 192 healthy controls were chosen in our study. The polymorphisms of exons 11 of MEF2A gene were genotyped by polymerase chain reaction-sequence-based typing (PCR-SBT). The relation of ischemic stroke caused by LAA with polymorphisms of (CAG)n was analyzed. Results Different (CAG)n alleles could be detected, with repeated sequences of 9-11. Frequencies for the different (CAG)n alleles in exon 11 CAG of MEF2A gene were not the same between the ischemic stroke patients and the controls (χ2=8.547, P=0.036). The distribution frequency of the (CAG)9 allele in the ischemic stroke group was significantly higher than that in the control group (χ2=6.650, P=0.010). Logistic regression analysis indicated that systolic pressure and (CAG)9 (OR=1.401, P=0.017, 95％CI: 1.063-1.847) were the independent risk factors of acute ischemic stroke caused by LAA. Conclusion The (CAG)n polymorphisms may be associated with ischemic stroke caused by LAA and the (CAG)9 allele may be one of the genetic susceptibility factors for this subtype of stroke.

Objective ToinvestigateanimportedcaseofZikavirusdiseaseinWenzhouCity,toexplorethesourceof infection,to analyse the problems during surveillance and diagnosis,and to provide evidence for prevention and control of Zikavirusdisease.Methods Byfieldinvestigation,medicalrecordsofthepatientwerecollectedandaface-to-face interview was conducted;blood,urine and saliva samples within 48 h were collected for RNA detection;assess the risk of diseasespreadingbymosquitosurveillanceandtakecontrolmeasures.Results Theonsetofthediseasewasonthepatient's way home from aboard on February 21st,2016.Before then,She lived in Paramaribo,the capital of Suriname in South America,which is an epidemic area of Zika virus.The patient had exposure history,with red,diffuse rash on her head,face, neck and limbs,and once was diagnosed as allergic eruption because of no fever.The two blood samples were both tested negative yet We detected urine and saliva samples showed positive.With the evidence above,the patient was finally diagnosed as an imported Zika virus case.The spreading risk of this case was low due to the low temperature.Conclusion there may be cases without fever or with blood sample tested RNA negative.As the weather gets warmer,missed diagnosis should be aware of,or the risk of spreading through mosquitos would increase.Therefore,in order to further improvement should lie in mosquito control and disease surveillance.

OBJECTIVETo explore the correlation between pathological characteristics of target organs and excess evil syndrome in IgA nephropathy.

METHODSData were collected in multicenter cooperation. Totally 266 IgA nephropathy patients were typed into exogenous wind-heat affection syndrome (49 cases), lower energizer damp-heat syndrome (100 cases), damp-phlegm syndrome (43 cases), and blood stasis syndrome (74 cases). Meanwhile, percutaneous renal biopsy was performed in all patients for Hass classification, Oxford classification, Katafuchi integral, and Jiang's classification methods. The correlation between excess evil syndrome and pathological index was analyzed.

RESULTSFour syndrome types were correlated with their Hass levels (r = 0. 341, P <0. 01). Affection of exogenous wind-heat syndrome was correlated with segmental proliferation of endothelial cells and damaged active lesions of segmental capillary loops. Lower-energizer damp-heat syndrome was associated with Hass III level, destroying active lesions of capillary loops, segmental proliferation of endothelial cells, glomerular segmental lesions, focal interstitial infiltration of inflammatory cells, focal interstitial fibrosis and tubular atrophy. Blood stasis syndrome was associated with Hass IV level, glomerular sclerosis, segmental glomerulosclerosis (S)/adhesion, mesangial hypercellularity (M), angiohyalinosis, multi-foci interstitial infiltration of inflammatory cells, multi-foci interstitial fibrosis and tubular atrophy. Phlegm-damp syndrome had higher proportions of Hass I and III levels, but with no association with other pathological parameters.

CONCLUSIONSExcess evil syndrome was associated with partial pathological characteristics of IgA nephropathy. It could reflect pathological damage degree of target organs, activities, chronic lesions, and prognosis of IgA nephropathy to certain extent. Correlated pathological characteristics and its evolution could indicate excess evil syndrome types and their evolution rules.

Capillaries ; Fibrosis ; Glomerulonephritis, IGA ; pathology ; Glomerulosclerosis, Focal Segmental ; Humans ; Kidney Glomerulus ; Medicine, Chinese Traditional ; Prognosis ; Syndrome

Objective Toinvestigatethestatusoftick-borneRickettsiaeinfectionsamongmurine-likeanimalsin differentareasofZhejiangprovince.Methods Liverandspleensamplesofmurine-likeanimalscapturedthroughnight trapping method were collected from Anji,Jinhua and Tiantai County according to their geographic locations and historical detection of Rickettsiae .Nest-PCR tests were used to determine the presence of the 16S rRNA genes of Anaplasma and Ehrlichia ,and the heat shock protein genes (groEL)of Rickettsiae (including typhus and spotted fever group)and Orientiainthesesamples.Results Atotalof851murine-likeanimalsbelongingto14specieswerecaptured.The predominant species were Rattus confucianus (30.32%),Apodemus agrarius (18.80%) and Thallomys paedulcus (1 1.75%)and they were significantly different among three areas (P<0.05 ).48 Rickettsia positive were found in 562 tested samples with the positive rate of 8.54%,among which the percentage of Anaplasma,typhus group Rickettsia, Orientia,Ehrlichia and spotted fever group Rickettsia were 3.38%,1.78%,1.78%,1.07% and 0.53% respectively. The positive rates of Anaplasma in Jindong (4.76%)and Anji (4.27%)were significantly higher than that in Tiantai (P<0.05 )while the spotted fever group Rickettsia were found only in Tiantai County.Moreover,Rattus confucianus-the predominant species of Zhejiang Province-had the highest infection rate of tick-borne Rickettsiae up to 14.97%.Co-infections with several Rickettsiae were existed among the same species.Conclusion Rickettsiae infections exist widely among different areas of Zhejiang province and the positive rates are significantly different among species.