Liver fibrosis is a dynamic wound-healing response characterized by the agglutination of the extracellular matrix (ECM). Si-Wu-Tang (SWT), a traditional Chinese medicine (TCM) formula, is known for treating gynecological diseases and liver fibrosis. Our previous studies demonstrated that long non-coding RNA H19 (H19) was markedly upregulated in fibrotic livers while its deficiency markedly reversed fibrogenesis. However, the mechanisms by which SWT influences H19 remain unclear. Thus, we established a bile duct ligation (BDL)-induced liver fibrosis model to evaluate the hepatoprotective effects of SWT on various cells in the liver. Our results showed that SWT markedly improved ECM deposition and bile duct reactions in the liver. Notably, SWT relieved liver fibrosis by regulating the transcription of genes involved in the cytoskeleton remodeling, primarily in hepatic stellate cells (HSCs), and influencing cytoskeleton-related angiogenesis and hepatocellular injury. This modulation collectively led to reduced ECM deposition. Through extensive bioinformatics analyses, we determined that H19 acted as a miRNA sponge and mainly inhibited miR-200, miR-211, and let7b, thereby regulating the above cellular regulatory pathways. Meanwhile, SWT reversed H19-related miRNAs and signaling pathways, diminishing ECM deposition and liver fibrosis. However, these protective effects of SWT were diminished with the overexpression of H19 in vivo. In conclusion, our study elucidates the underlying mechanisms of SWT from the perspective of H19-related signal networks and proposes a potential SWT-based therapeutic strategy for the treatment of liver fibrosis.
Humans ; RNA, Long Noncoding/genetics* ; Liver Cirrhosis/genetics* ; Liver/metabolism* ; Hepatic Stellate Cells/pathology* ; MicroRNAs/metabolism* ; Extracellular Matrix/metabolism* ; Drugs, Chinese Herbal

OBJECTIVE To study the relationship between serum CC type chemotactic factor 2(CCL2),CC type chemotactic factor 18(CCL18) and clinicopathological parameters and prognosis of patients with glottic carcinoma. METHODS A total of 168 glottic carcinoma patients admitted to Handan Central Hospital and Hebei Engineering University Affiliated Hospital from August 2015 to December 2018 were selected as the research subjects. The receiver operating characteristic(ROC) curve was used to determine the optimal cut-off points for serum CCL2 and CCL18. Based on this,patients were divided into CCL2 high expression group and low expression group,CCL18 high expression group and low expression group. The relationship between levels of serum CCL2 and CCL18 and clinical pathological parameters of glottic carcinoma patients was analyzed. Kaplan-Meier curve and Log Rank x2 test were used to analyze the 5-year disease-free survival rate of serum CCL2 high/low expression group and CCL18 high/low expression group. Cox regression model was used to analyze the influencing factors of glottic carcinoma prognosis,and the relationship between serum CCL2,CCL18 expression and tumor recurrence/metastasis was analyzed. RESULTS The optimal cut-off points for CCL2 and CCL18 calculated based on the ROC curve were 100.81 and 218.99 pg/ml,respectively. Compared with the low expression groups of CCL2 and CCL18,the high expression groups of CCL2 and CCL18 showed a significant increase in the proportion of T3-T4a,N1-N3 stages,and tumor low differentiation(P<0.05). Of the 168 glottic carcinoma patients,there were 160 patients followed up for 5 years and 8 patients lost for follow-up. There were 67 patients experienced recurrence or metastasis,and 39 patients died due to recurrence or metastasis. The tumor recurrence or metastasis rate was 41.88％(67/160),and the disease-free survival rate was 58.13％(93/160). Kaplan-Meier survival curve analysis showed that the 5-year disease-free survival rate of the high expression group of serum CCL2 and CCL18 was significantly lower than that of the low expression group of serum CCL2 and CCL18(P<0.05). Cox regression analysis showed that elevated T staging,cervical lymph node recurrence,elevated N staging,local recurrence,high expression of CCL2 and CCL18 were risk factors for poor prognosis in glottic carcinoma(P<0.05). For analysis the relationship between serum CCL2 and CCL18 expression and tumor recurrence or metastasis,it was found that when both CCL2 and CCL18 were highly expressed,the recurrence or metastasis rate was significantly higher than when both CCL2 and CCL18 were lowly expressed,CCL2 was lowly expressed and CCL18 was highly expressed,and CCL2 was highly expressed and CCL18 was lowly expressed,and the differences were statistically significant(x2=10.450,P=0.015). CONCLUSION The high expression of serum CCL2 and CCL18 in patients with glottic carcinoma is significantly correlated with T stage,N stage,tumor low differentiation,and poor prognosis.

Background It is projected that the frequency, density, and duration of compound hot extreme may increase in the 21st century in the context of global warming. Objective To explore the association between compound hot extreme and blood pressure, and identify sensitive populations. Methods This was a cross-sectional study. The study subjects were from six Guangdong Province Chronic Disease and Nutrition Surveys during 2002 through 2015. A questionnaire was administered to the participants with questions about demographic information, drinking and smoking status, and measurements on their height, weight, and blood pressure were also collected. We chose the data of May, September, and October to explore the association between compound hot extreme and blood pressure. Compound hot extreme means a hot day with a proceeding hot night. Daily meteorological data were obtained from China Meteorological Data Service Centre. We employed inverse distance weighting to interpolate the temperature and relative humidity values for each participant. A distributed lag non-linear model was used to estimate the association between compound hot extreme and blood pressure. Stratified analyses by sex, age, area, body mass index (BMI), smoking status, and drinking status were also performed to identify sensitive populations. A sensitivity analysis was conducted by adjusting the degrees of freedom for lag spline and removing relative humidity. Result A total of 10967 participants without history of hypertension were included in this study. The average systolic blood pressure (SBP) was 120.8 mmHg and the average diastolic blood pressure (DBP) was 74.5 mmHg. The proportion of participants who experienced hot day, hot night, or compound hot extreme were 9.34%, 17.95% and 2.90%, respectively. Compared to hot day, hot night and compound hot extreme were related with decreased blood pressure, and the effect of compound hot extreme was stronger: the changes and 95%CI for SBP was −6.2 (−10.3-−2.1) mmHg, and for DBP was −2.7 (−5.2-−0.2) mmHg. Compound hot extreme induced decreased SBP among male, population ≥ 65 years, and those whose BMI < 24 kg·m^-2, and their ORs (95%CIs) were −6.2 (−10.7-−1.6). −19.1 (−33.0-−5.1), and −6.7 (−11.8~−1.6) mmHg, respectively, and also decreased DBP among population ≥ 65 years, and its OR (95%CI) was −8.4 (−15.6-−1.1) mmHg. During compound hot extremes, participants living in rural areas showed decreased SBP and DBP, and the ORs (95%CIs) were −10.5 (−16.6-−4.5) and −4.4 (−7.7-−1.1) mmHg respectively, while those living in urban areas showed increased SBP, and the OR (95%CI) was 9.7 (2.9-16.5) mmHg. A significant decrease in blood pressure [OR (95%CI)] was also found in non-smokers [DBP, −3.7 (−6.6-−0.8) mmHg] and non-drinkers [SBP, −4.8 (−9.4-−0.2) mmHg; DBP, −3.4 (−6.0-−0.9) mmHg]. Conclusion Compound hot extreme is negatively associated with SBP, and being male, aged 65 years and over, and having BMI < 24 kg·m⁻² may be more sensitive to compound hot extreme.

Background Under the background of global climate change, temperature has increased dramatically. Most studies about association between temperature and human health are conducted in low-altitude areas, but rarely focus on plateau areas. Objective To examine the association between temperature and non-accidental mortality risk in Tibet Plateau, China and to identify vulnerable populations for formulating targeted policies of climate change adaptation. Methods The mortality data, meteorological data, and pollutant data of Tibet area between 2013 to 2019 were collected. Based on time-stratified case-crossover design, conditional logistic regression models were used to analyze the exposure-response relationship between temperature and cause-specific mortality, which was linearized to obtain excess risk for 1 ℃ change; attributable fraction was calculated for assessing burden attributable to temperature; and stratified analyses were further conducted by gender, age (＜65 years old, ≥65 years old), and causes of death (cardiovascular diseases, cerebrovascular diseases, and respiratory diseases). Sensitivity analyses were conducted by adjusting model parameters and variables. Results A total of 26 045 non-accidental deaths were collected in Tibet during 2013 and 2019, and the P₅₀ of temperature was 5.0 ℃. The non-accidental mortality risk increased as temperature become colder. A 1 ℃ decrease in temperature was associated with a 2.01% (95%CI: 0.94%-3.07%) increase in total non-accidental mortality, while the association changed to 2.05% (95%CI: 0.62%-3.47%) for male and 1.96% (95%CI: 0.34%-3.56%) for female, both of statistial significance; 1.45% (95%CI: −0.10%-2.98%) for the people <65 years old (not of significance) and 2.52% (95% CI : 1.04%-3.99%) for the people ≥65 years old (of significance); the excess risk for cardiovascular mortality was 2.65% (95%CI: 1.03%-4.24%), for cerebrovascular mortality was 3.70% (95%CI: 0.74%-6.57%), both of statistical significance, and for respiratory mortality was 2.18% (95%CI: −0.14%-4.44%), without significance. The total attribution number of non-accidental mortality was 5340 (95%CI: 2719-7528), and the total attributable fraction was 20.50% (95%CI: 10.44%-28.91%). The attributable fractions were higher in specific subgroups like male (20.72%), people ≥65 years (23.33%), and people with cardiovascular diseases (26.07%). Conclusion The exposure-response relationship between temperature and non-accidental mortality in Tibet showes that the non-accidental mortality risk increase as temperature become colder. The attributable burden of disease is heavy. Residents being male, ≥65 years, with cardiovascular diseases and respiratory diseases may be vulnerable to nonoptimal temperature.

Background Global warming may increase the frequency of compound hot extreme (CHE).However, there is still a lack of studies assessing the associations between CHE and preterm birth (PTB), and the underlying biological mechanisms remain unclear. Objective To estimate the association of exposure to CHE during pregnancy with PTB, and to explore the roles of inflammatory, endothelial dysfunction, and oxidative stress in the association between CHE and PTB. Methods All participants were selected from the Prenatal Environments and Offspring Health (PEOH), a prospective birth cohort conducted in Guangzhou. In this study, a total of 2449 participants who gave birth from May to October in 2014 to 2017 were enrolled, and among them blood samples were collected from 311 preterm (n=43) and full-term (n=268) pregnant women at the time of delivery. A hot day/night was identified as a day when the daily maximum temperature/minimum temperature was higher than its 90th percentile in the study period, and a CHE was defined as having both a hot night and a following hot day. The meteorological data were obtained from the China Meteorological Data Sharing Service System. Anusplin was used to assess the daily maximum temperature, daily minimum temperature, and relative humidity of the participant residence. Enzyme-linked immunosorbent assay (ELISA) was used to measure C reactive protein (CRP), endothelin-1 (ET-1), and malondialdehyde (MDA) levels in maternal serum, and their results were transformed by natural logarithm. A distributed lag nonlinear model was used to investigate the associations of exposures to hot day, hot night, and CHE during pregnancy with PTB at different lag days, and a logistic regression model was used to investigate the associations of CRP, ET-1, and MDA with PTB. Results The incidence rate of PTB was 6.2% in all selected participants. Compared with the non-hot day, the RRs (95%CIs) of CHE in lag 3, 7, and 14 days on PTB were 1.43 (1.12-1.84), 1.24 (1.08-1.43), and 1.17 (1.05-1.30), respectively, and the cumulative effects (% difference) (95%CI) of CHE in lag 14 days on maternal serum CRP, ET-1, and MDA were 0.33% (−0.45%-1.12%), 0.59% (0.11%-1.07%), and 0.57% (0.09%-1.05%), respectively. Compared with the Q1 (lowest quartile) for CRP, ET-1 and MDA, the RRs (95%CIs) of Q4 (highest quartile) for PTB were 1.27 (0.50-3.22), 1.51 (0.61-3.72), and 2.07(0.81-5.27), respectively. Conclusion Maternal exposure to CHE during pregnancy might be associated with an increased risk of PTB. Prenatal exposure to CHE is positively associated with maternal serum CRP, ET-1, and MDA, and the three biochemical indicators are also positively associated with PTB. However, the above conclusions still need further confirmation.

The study of distinct genes, chromosomes and the spatio-temporal relationships between them is of great significance in genetics, developmental biology and biomedicine. CRISPR/Cas9 has become the most widely used gene editing tool due to its excellent targeting ability. Recently, researchers have developed a series of advanced live cell imaging techniques based on the nuclease-inactivated mutant of Cas9 (dCas9), providing rapid and convenient tools for high-resolution imaging of specific sites in the chromatin and genome. This review summarizes the advances of CRISPR/dCas9 system in live cell imaging from three aspects, including the strategies of cell delivery, optimization of the fluorescence signals, as well as orthogonal and multicolor imaging. Furthermore, we shed light on the development trends and prospects of this field.
CRISPR-Cas Systems/genetics* ; Chromatin ; Endonucleases ; Gene Editing

Objective To analyze the bloodstream infections caused by vancomycin‐resistant Enterococcus (VRE)in West China Hospital and examine the risk factors of such infections for best control of VRE infections .Methods Case‐control method was used to compare the bloodstream infections due to VRE with those caused by vancomycin‐susceptible Enterococcus(VSE)from August 2010 to August 2014 in West China Hospital .The data were compared by T‐test ,Chi‐square test (univariate analysis) and logistic regression analysis (multivariate analysis) using SPSS 19 .0 software .Results A total of 31 VRE strains were isolated from bloodstream infections in the study period ,including 5 (16 .1 % ) strains of vancomycin‐resistant Enterococcus faecalis and 26 (83 .9 % )strains of vancomycin‐resistant Enterococcus faecium .In the past four years ,the prevalence of vancomycin‐resistant E . f aecalis in bloodstream infections was 1 .5% ,1 .6% ,1 .8% ,and 1 .2% ;while the prevalence of vancomycin‐resistant E . f aecium in bloodstream infections was 3 .8% ,4 .4% ,5 .8% ,and 7 .1% .Such VRE bloodstream infection was mainly found in Intensive Care Unit (ICU)(13 ,41 .9% )and Department of Neurosurgery (4 ,12 .9% ) .More than 90% of the isolates were resistant to ampicillin and erythromycin .But less than 20% of the strains were resistant to quinupristin‐dalfopristin and linezolid . Univariate analysis indicated that prolonged hospital stay , ICU admission , venous catheter ,prior carbapenem exposure , prior vancomycin/norvancomycin exposure were associated with VRE bloodstream infections .Logistic regression analysis confirmed that venous catheter was an independent risk factor of VRE bloodstream infections .Conclusions Venous catheter is an independent risk factor for VRE bloodstream infections . Infection control measures should be strengthened to prevent the outbreak of VRE‐related bloodstream infections .

Objective To investigate the clinical efficacy of the urethra URSL combined with micro-puncture and drainage treatment for pediatric calculus of lower urinary tract. Methods From January 2003 to January 2013, 66 cases with pediatric urinary tract calculi in our hospital were randomly equally divided into experimental group and control group. The experimental group was treated with transurethral bladder micro URSL combined puncture and drainage treatment, and the control group was given a simple transurethral URSL method of treatment. The operative time, postoperative urine turned clear time,pulling stone clearance after catheter time,postoperative hospital stay and the incidence of postoperative urethral stricture were observed and recorded. In addition, these data were compared between the two groups. Results The operations of two groups have successfully completed. The mean operative time, postoperative urine turned clear time, pull out the catheter stone clearance after time and postoperative hospital stay of control group was 30.2±2.45 minutes,2.5±0.5 days,2.1±0.8 days and 4.0±0. 5 days, respectively. Patients were followed up 1 year after operation, and 1 case of urethral stricture occurred. However, the mean operative time, postoperative urine turned clear time, pull out the catheter stone clearance after time and postoperative hospital stay of the test group was 20.36±2.35 minutes,1.5±0.7 days,1.1±0.25 days and 3.1±0.3 days,respectively,with no urethral stricture case occurred. There were significant differences between the two groups ( <0.05) . Conclusion Transurethral bladder URSL micro puncture and drainage combined with transurethral ureteroscopy lithotripsy treatment for children with lower urinary tract calculi has better efficacy and safety. It could shorter operative time, postoperative urine turned clear time, the gravel discharge time and average hospitalization time, reduce the incidence of postoperative secondary urethral stricture.

Objective To investigate the feasibility and safety of endoscopic treatment of ureteral calculi acute obstruction with urinary extravasation. Methods 56 patients with ureteral calculi acute obstruction and urinary extravasation were randomly divided into two groups:the treatment group and the control group,28 cases in each group. Patients in the treatment group were given URSL or percutaneous nephrostomy drainage, and the secondary fistula was given URSL stone clearance treatment. Patients in control group were given traditional ureterolithotomy treatment. The stone clearance rate, the average recovery time after surgery, postoperative wound infection rate and the abnormal rate of postoperative albumin were observed in two groups. Results In the treatment group,28 patients had no residual stones with mean postoperative recovery time of (5.2 1.3) days,postoperative fever was found in 3 cases,obvious abnormal postoperative albumin in 3 cases. In the control group,residual stones were found in 3 cases,the average recovery time after surgery was (7.9 2.6) days,postoperative fever was found in 10 cases, and obvious abnormal postoperative albumin in 11 cases. There were statistically significant differences in stone clearance rate, the average recovery time after surgery, postoperative wound infection rate and the abnormal rate of postoperative albumin between two groups (P<0.05) . Conclusion Endoscopic treatment of ureteral calculi acute obstruction and urinary extravasation has advantages including better efficacy, less trauma, less complications and quicker recovery.

The sigma-1 receptor is a molecular chaperone protein highly enriched in the brain. Recent studies linked it to many diseases, such as drug addition, Alzheimer's disease, stroke, depression, and even cancer. Sigma-1 receptor is enriched in lipid rafts, which are membrane microdomains essential in signaling processes. One of those signaling processes is ADAM17- and ADAM10-dependent ectodomain shedding. By using an alkaline phosphatase tagged substrate reporter system, we have shown that ADAM10-dependent BTC shedding was very sensitive to both membrane lipid component change and sigma-1 receptor agonist DHEAS treatment while ADAM17-dependent HB-EGF shedding was not; and overexpression of sigma-1 receptor diminished ADAM17- and ADAM10-dependent shedding. Our results indicate that sigma-1 receptor plays an important role in modifying the function of transmembrane proteases.
ADAM Proteins ; metabolism ; ADAM10 Protein ; ADAM17 Protein ; Amyloid Precursor Protein Secretases ; metabolism ; Animals ; Betacellulin ; COS Cells ; Cercopithecus aethiops ; Gene Expression ; HEK293 Cells ; Heparin-binding EGF-like Growth Factor ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Membrane Microdomains ; metabolism ; Membrane Proteins ; metabolism ; Receptors, sigma ; agonists ; metabolism