Caffeic acid phenethyl ester improves peritoneal dialysis-associated peritoneal fibrosis by alleviating oxidative stress injury through activating nuclear factor erythroid-2-related factor 2/heme oxygenase-1 pathway / 中华肾脏病杂志

Objective:To investigate whether caffeic acid phenethyl ester (CAPE) would improve peritoneal dialysis (PD)-associated peritoneal fibrosis by alleviating oxidative stress through activating nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway.Methods:Thirty-two male Sprague-Dawley rats were randomly divided into four groups by the random number table: control (CON) group (0.9% normal saline 20 ml/d intraperitoneal injection), CAPE group (0.9% normal saline 20 ml/d+CAPE 10 mg·kg -1·d -1 intraperitoneal injection), PD group [4.25% glucose peritoneal dialysis fluid (PDF) 20 ml/d intraperitoneal injection with lipopolysaccharide 0.6 mg/kg intraperitoneal injection at day 1, 3, 5 and 7], and PD+CAPE group (CAPE 10 mg·kg -1·d -1 intraperitoneal injection in addition to PD group), with 8 rats per group. On day 28, rats were euthanized after peritoneal equilibration test, and then the parietal peritoneum and omentum were collected for follow-up tests. To further investigate the mechanism, primary peritoneal mesothelial cells (PMCs) of rats were isolated and cultured. The PMCs were stimulated with 2.5% glucose PDF and added with 5 μmol/L CAPE intervention. The Nrf2 inhibitor (ML385) was used to identify whether CAPE protected PMCs from PDF by activating the Nrf2/HO-1 pathway. Histopathological staining was used to detect structural changes of the peritoneum, and immunohistochemical analysis was performed on cleaved caspase-3, Bax, α-smooth muscle actin (α-SMA), fibronectin (FN), and typeⅠ collagen (Col-Ⅰ) protein. Western blotting was used to detect the protein expression of α-SMA, FN, transforming growth factor-β1 (TGF-β1), HO-1 and nuclear Nrf2 (N-Nrf2). The apoptosis detection kit was used to detect apoptosis and flow cytometry was used to detect reactive oxygen species (ROS) in PMCs. The malondialdehyde (MDA) and superoxide dismutase (SOD) activity detection kit were used to detect MDA content and SOD activity. Cell immunofluorescence was used to analyze the protein expression of Nrf2 in PMCs. Results:Compared with the CON group, the PD group had thicker peritoneum, and the expression levels of cleaved caspase-3, Bax, α-SMA, FN, Col-Ⅰand MDA in peritoneum were significantly higher, while HO-1, N-Nrf2 protein expression and SOD activity were lower (all P<0.05). Compared with the PD group, the parietal peritoneum morphology of CAPE+PD group was improved, accompanied by reduced cleaved caspase-3, Bax, α-SMA, FN, Col-Ⅰ protein expression, and MDA content, while N-Nrf2, HO-1 protein expression, and SOD activity were higher (all P<0.05). Compared with the CON group, the PD group had significantly lower ultrafiltration volume and higher peritoneal permeability (both P<0.05). After CAPE intervention, the peritoneal transport function of the rats was significantly improved ( P<0.05). In cultured PMCs, PDF inhibited nuclear translocation of Nrf2 and protein expression of HO-1, and upregulated intracellular ROS level. In addition, PDF increased cell apoptosis and the protein expression levels of α-SMA, TGF-β1 and FN (all P<0.05). CAPE activated nuclear translocation of Nrf2, increased HO-1 protein expression, downregulated intracellular ROS level, and partially reversed PDF-induced cell apoptosis and epithelial- mesenchymal transition (all P<0.05). The protective effects of CAPE on PMCs were partially abolished by ML385 (all P<0.05). Conclusions:CAPE can reduce PD-induced PMCs apoptosis and epithelial-mesenchymal transition by attenuating oxidative stress, and significantly improve peritoneal fibrosis and ultrafiltration function. The beneficial effects of CAPE on peritoneum are related to activation of Nrf2/HO-1 pathway.

Application of supraclavicular fasciocutaneous island flap for reconstruction after removal of tumors in parotid and auricle area / 中华耳鼻咽喉头颈外科杂志

Objective: To evaluate the efficacy of supraclavicular fasciocutaneous island flap (SIF) for repairing the defect of parotid or auricle regions after tumor resection. Methods: From February 2019 to June 2021, 12 patients (11 males and 1 female, aged 54-77 years old), of whom 4 with parotid adenoid cystic carcinoma and 8 with auricular basal cell carcinoma underwent reconstruction surgery for postoperative defects in the parotid gland area and auricular area with SIF in the Department of Otorhinolaryngology Head and Neck Surgery, the Second Xiangya Hospital of Central South University and their clinical data were retrospectively analyzed. Size of the SIF, time for harvesting SIF, neck lymph node dissection and postoperative complications were recorded. Results: The flap areas were (6-9) cm × (8-13) cm, and the harvesting time for SIF ranged from 40 to 80 min, averaging 51.7 min. The donor sites were directly closed. All patients underwent ipsilateral levels Ⅰ-Ⅲ neck dissection, with 4 cases undergoing additional level Ⅳ neck dissection and 2 cases undergoing level Ⅳ-Ⅴ neck dissection. Of the 12 SIF, 10 were completely survival and 2 had flap arterial crisis with partial flap necrosis, in addition, 1 had donor site wound dehiscence. With follow-up of 10-42 months, there were no tumor recurrences in 10 patients, 1 patient was lost to follow-up at 10 months postoperatively, and 1 patient experienced local tumor recurrence at 11 months after surgery and died 15 months later. Conclusion: SIF is an easily harvested flap with good skin features matching the skin in parotid and auricle regions and less damage to donor site, and this flap has no need for microvascular anastomosis technique. SIF is feasible and effective for repairing defects in parotid and auricle area.

Effect of Shengmai Yin on Epithelial-Mesenchymal Transition of Nasopharyngeal Carcinoma Radioresistant Cells / 中国结合医学杂志

OBJECTIVE@#To investigate the mechanism by which Chinese medicine Shengmai Yin (SMY) reverses epithelial-mesenchymal transition (EMT) through lipocalin-2 (LCN2) in nasopharyngeal carcinoma (NPC) cells CNE-2R.@*METHODS@#Morphological changes in EMT in CNE-2R cells were observed under a microscope, and the expressions of EMT markers were detected using quantitative real-time PCR (RT-qPCR) and Western blot assays. Through the Gene Expression Omnibus dataset and text mining, LCN2 was found to be highly related to radiation resistance and EMT in NPC. The expressions of LCN2 and EMT markers following SMY treatment (50 and 100 µ g/mL) were detected by RT-qPCR and Western blot assays in vitro. Cell proliferation, migration, and invasion abilities were measured using colony formation, wound healing, and transwell invasion assays, respectively. The inhibitory effect of SMY in vivo was determined by observing a zebrafish xenograft model with a fluorescent label.@*RESULTS@#The CNE-2R cells showed EMT transition and high expression of LCN2, and the use of SMY (5, 10 and 20 µ g/mL) reduced the expression of LCN2 and reversed the EMT in the CNE-2R cells. Compared to that of the CNE-2R group, the proliferation, migration, and invasion abilities of SMY high-concentration group were weakened (P<0.05). Moreover, SMY mediated tumor growth and metastasis in a dose-dependent manner in a zebrafish xenograft model, which was consistent with the in vitro results.@*CONCLUSIONS@#SMY can reverse the EMT process of CNE-2R cells, which may be related to its inhibition of LCN2 expression. Therefore, LCN2 may be a potential diagnostic marker and therapeutic target in patients with NPC.

3-bromopyruvate cholesterol ester enhances the sensitivity of breast cancer cells to tamoxifen / 中国临床药理学与治疗学

AIM: To investigate the effect of 3-bro-mopyruvate cholesterol ester (3-BP-Cl) on the sensitivity of breast cancer to tamoxifen (TAM). METHODS: MTT assay and Calcein AM/PI staining were used to detect the effect of drugs on the viability of breast cancer cells. Kim's formula was used to detect synergistic anti-breast cancer effect of cholesterol 3-bromopyruvate and tamoxifen. The inhibitory effect of drugs on proliferation of breast cancer cells was detected by colony-forming assay. Flow cytometry was used to detect the apoptosis of breast cancer cells. Western blot assay was used to detect the expression of hexokinase 2, Bcl-2 and Bax proteins. RESULTS: MTT results showed that combination 3-BP-Cl and TAM could significantly inhibit the activity of MCF-7 cells (P1.15). Calcein AM / PI staining showed that the number of dead cells was the highest in the combination group. Colony-forming assay showed that the combination group had stronger inhibitory effect on the proliferation of MCF-7 cells than that of single drug groups. AnnexinV flow cytometry results showed that, the cell apoptosis in the combination group was significantly increased (P<0.01). Western blot results showed that 3-BP-Cl inhibited the expressions of hexoktokinase 2 and Bcl-2, and enhanced the expression of Bax in MCF-7 cells. CONCLUSION: 3-BP-Cl could increase the sensitivity of breast cancer cells to tamoxifen, and synergically inhibit the proliferation of breast cancer cells. The mechanism is possibly related to its effects of inhibiting the expression of HK2/Bcl-2, and enhancing the expression of Bax.

Self-Appraisal of Clinical Competence in Echocardiography of Chinese Intensivists Post Basic Echocardiography Training / 中国医学科学杂志(英文版)

Objectives To learn the echocardiography skills of intensivists after receiving a basic critical care echocardiography training course, and investigate factors that may influence their performance. Methods We completed a web-based questionnaire that assessed the skills in ultrasound scanning techniques of intensivists who took a training course on basic critical care echocardiography held in 2019 and 2020. Mann-Whitney test was used to analyze the factors which might affect their performance on image acquisition, recognizing clinical syndrome, and measuring the diameter of inferior vena cava, left ventricular ejection fraction and left ventricular outflow tract velocity-time integral.Results We enrolled 554 physicians from 412 intensive care units across China. Among them, 185 (33.4%) reported that they had 10%-30% chance of being misled by critical care echocardiography when making therapeutic decision, and 34 (6.1%) reported that the chance was greater than 30%. Intensivists who performed echocardiography under the guidance of a mentor and finished ultrasound scanning more than 10 times per week reported significant higher scores in image acquisition, clinical syndrome recognition, and quantitative measurement of inferior vena cava diameter, left ventricular ejection fraction and left ventricular outflow tract velocity-time integral than those without mentor and performing echocardiography 10 times or less per week respectively (all P < 0.05).Conclusion The skills in diagnostic medical echocardiography of Chinese intensivists after a basic echocardiographic training course remain low, and further quality assurance training program is clearly warranted.

Research progress in chemical constituents, pharmacological effects, and clinical application of Curcuma wenyujin and prediction of its quality markers / 中国中药杂志

Curcuma wenyujin, as one of the eight Daodi-herbs in Zhejiang province, is widely used. It has the effects of eliminating stasis and dissipating mass, moving Qi and activating blood, and clearing heart and relieving depression. Modern studies have shown that it has anti-tumor, anti-inflammatory, anti-oxidation, anti-thrombus and liver-protecting effects and mainly contains sesquiterpenoids, monoterpenoids, diterpenoids, and curcumins. This paper reviews the research progress in the chemical constituents and pharmacological effects of C. wenyujin in the last decade, discusses the modern clinical applications combined with the traditional efficacy, and predicts its quality markers(Q-markers) from plant consanguinity, medicinal properties, efficacy, processing and measurability of chemical components based on the theory of Q-markers, so as to provide a reference for the establishment of a scientific quality evaluation system and the research and application of this herb in the future.

C-reactive protein to albumin ratio is an independent influencing factor of mortality in peritoneal dialysis patients / 中华肾脏病杂志

Objective:To investigate the association between C-reactive protein (CRP)/albumin (ALB) ratio (CAR) and mortality in peritoneal dialysis (PD) patients.Methods:Clinical data of 791 PD patients in the Second Affiliated Hospital of Soochow University from January 1, 2004 to December 31, 2019 were retrospectively collected. According to the baseline quartiles of CAR, patients were divided into three groups: low-level CAR group (CAR≤0.161 mg/g, n=264), medium-level CAR group (CAR 0.162-0.214 mg/g, n=263) and high-level CAR group (CAR≥0.215 mg/g, n=264). The clinical data among the three groups were compared. Follow-up was ended on March 31, 2020, or when the patients stopped PD due to death, shift to hemodialysis, renal transplantation or recovery of renal function. Kaplan-Meier survival curve, multivariate Cox proportional hazard model and Fine-Gray competing risk model were used to assess the relationship between CAR and all-cause mortality and cardiovascular and cerebrovascular mortality. The association between CAR, CRP, ALB, neutrophil to lymphocyte ratio (NLR), or platelet to lymphocyte ratio (PLR) and mortality in PD patients was compared by receiver-operating characteristic curve (ROC curve) analysis. Results:The age of the patients was (59.8±15.7) years old, and 447(56.5%) patients were males. 714(90.3%) patients had hypertension. 233(29.5%) patients had diabetes. 182(23.0%) patients had cardiovascular diseases. The median follow-up time was 55(31, 88) months. By the end of the follow-up, 236 deaths (29.8%) happened, and 95 patients (12.0%) died from cardiovascular and cerebrovascular diseases. Kaplan-Meier survival analysis results showed that the overall survival rate of the high-level CAR group was lower than those of the low-level CAR group and medium-level CAR group (Log-rank test χ2=109.50, P<0.001). Multivariate Cox regression analysis and Fine-Gray competing risk model revealed that CAR was independently correlated with all-cause mortality and cardiovascular and cerebrovascular mortality after adjusting for confounding factors ( HR=2.891, 95% CI 1.921-4.351, P<0.001; SHR=1.297, 95% CI 1.128-1.490, P<0.001). ROC curve analysis results showed that the area under the curve ( AUC) of CAR for predicting the risk of all-cause mortality in PD patients was 0.737(95% CI 0.700-0.774), which was superior to those of CRP ( AUC=0.643, 95% CI 0.599-0.687), NLR( AUC=0.608, 95% CI 0.563-0.653) and PLR ( AUC=0.554, 95% CI 0.508-0.601), and slightly lower than ALB ( AUC=0.752, 95% CI 0.716-0.788). The optimal cutoff value of CAR for death was 0.19 mg/g, with the sensitivity and specificity of 70.8% and 68.3%, respectively. Conclusions:Increasing CAR level is an independent risk factor of all-cause mortality and cardiovascular and cerebrovascular mortality in PD patients, and its correlation with mortality is higher than those of inflammatory parameters such as CRP, NLR and PLR.

Value of Endocervical Curettage in Detection of High-grade Cervical Squamous Intraepithelial Lesion / 肿瘤防治研究

Objective To explore the value of endocervical curettage (ECC) in the detection of high-grade cervical squamous intraepithelial lesion (HSIL). Methods We retrospectively analyzed the clinical features and colposcopical characteristics of 678 female patients with complete clinical data. Results Among 678 cases, 391 cases were confirmed by cervical biopsy only and 7 cases by ECC only (57.67% vs. 1.03%, P < 0.001). ECC checked out 287 HSIL patients (42.33%, including cervical biopsy positive and negative cases) and cervical biopsy checked out 671 HSIL cases (98.97%, including ECC positive and negative cases). There were 68 positive ECC cases in the conversion area of Type 1+Type 2 and 247 positive ECC cases in the conversion area of Type 3(33.33% vs. 52.11%, P < 0.001). The positive rates of ECC in patients≥45 years old and < 45 years old were 145 and 170, respectively (55.13% vs. 40.96%, P < 0.001). Conclusion The cervical biopsy plays a dominant role in the detection of HSIL, and ECC can only be used as a supplement to it. Female patients older than 45 years or with Type 3 transformation zone examined by colposcopy should be concerned with cervical lesions.

Screening of DNA methylation sites associated with melanoma and construction of an aberrant methylation profile: a preliminary study / 中华皮肤科杂志

Objective:To screen aberrant DNA methylation sites associated with melanoma using gene chip technology, and to preliminarily construct a melanoma-specific methylation profile.Methods:The Illumina Human Methylation 450K whole-genome methylation chip was used to detect the whole-genome DNA in 6 melanoma tissues and their paralesional skin tissues, and DNA differentially methylated sites were obtained. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) -based pathway analysis were carried out to investigate gene functions.Results:Gene chip testing showed that there were 27 779 differentially methylated sites between melanoma tissues and paralesional tissues, of which 16 673 were hypermethylated sites and 11 106 were hypomethylated sites in melanoma tissues. According to more stringent screening criteria " P < 0.01 and |Δβ| > 0.2", a total of 4 883 differentially methylated sites were screened out after filtering out all single nucleotide polymorphism-related probes, probes located on the XY chromosomes and cross-reactive probes, 1 459 (30%) of which were located in the promoter region including TSS1500, TSS200, 5′UTR and 1st Exon. GO enrichment analysis showed that differentially methylated genes were involved in many biological processes, including cell growth, differentiation, adhesion, movement and migration, signal transduction, transcriptional regulation, etc. KEGG-based pathway analysis showed that differentially methylated genes were mainly involved in signaling pathways, such as focal adhesion pathway, cancer pathways, transforming growth factor-β signaling pathway, phosphatidylinositol signaling pathway, melanogenesis pathway, chemokine signaling pathway, adhesion junction pathway, calcium signaling pathway, cell adhesion molecule pathway, mitogen-activated protein kinase signaling pathway, Wnt signaling pathway, Janus kinase-signal transducer and activator of transcription signaling pathway. Based on the criteira "the top 16 most differentially methylated genes related to hypermethylated sites in the promoter region, the genes with the highest methylation frequency (CpG sites ≥ 7) , the genes with certain functions or involved in a certain signaling pathway", 8 genes (KAAG1, DGKE, SOCS2, TFAP2A, GNMT, GALNT3, ANK2 and HOXA9) were selected as candidate biomarkers for melanoma. Conclusion:There are many hypermethylated genes in melanoma tissues, and 8 differentially methylated genes may serve as biomarkers for melanoma.

Effects of medroxyprogesterone acetate combined with a levonorgestrel-releasing intrauterine contraceptive system on sex hormone and vascular endothelial growth factor levels after laparoscopic surgery for moderate and severe endometriosis / 中国基层医药

Objective:To investigate the effects of medroxyprogesterone acetate combined with a levonorgestrel-releasing intrauterine contraceptive system (Mirena) on the levels of sex hormone and vascular endothelial growth factor in patients with moderate and severe endometriosis after laparoscopic surgery.Methods:A total of 102 patients with endometriosis who received laparoscopic conservative surgery in Hangzhou Ninth People's Hospital from October 2015 to May 2018 were retrospectively analyzed. They were randomly assigned to undergo either medroxyprogesterone acetate treatment alone (control group, n = 51) or medroxyprogesterone acetate treatment + levonorgestrel-releasing intrauterine contraceptive system application (observation group, n = 51) for 6 successive months. Clinical efficacy, serum luteinizing hormone, follicle-stimulating hormone, estradiol and vascular endothelial growth factor levels, Visual Analogue Scale score, endometriosis recurrence rate, and adverse reactions were compared between the control and observation groups. Results:Total effective rate in the observation group was significantly higher than that in the control group [94.12% (48/51) vs. 80.93% (41/51), χ2 = 4.320, P < 0.05]. At 6 months after surgery, serum luteinizing hormone, follicle-stimulating hormone, estradiol and vascular endothelial growth factor levels in the observation group were (5.72 ± 0.53) U/L, (5.05 ± 0.91) U/L, (156.02 ± 21.80) pmol/L and (155.39 ± 24.72) ng/L respectively, which were significantly lower than those in the control group [(6.51 ± 0.67) U/L, (5.73 ± 0.68) U/L, (177.20 ± 23.20) pmol/L and (186.22 ± 28.14) ng/L, t = 6.604, 4.275, 4.747 and 5.878, all P < 0.05). At 3 and 6 months after surgery, Visual Analogue Scale score in the observation group were (2.39 ± 0.33) points and (1.27 ± 0.20) points respectively, which were significantly lower than those in the control group [(2.72 ± 0.40) points, (1.52 ± 0.25) points, t = 4.545 and 5.577, both P < 0.05]. Two-year follow-up results revealed that endometriosis recurrence in the observation group was significantly lower than that in the control group [1.96% (1/51) vs. 13.73% (7/51), χ2 = 4.883, P < 0.05]. There was no significant difference in total incidence of adverse reactions between the two groups [15.69% (8/51) vs. 13.73% (7/51), χ2 = 0.078, P > 0.05]. Conclusion:Application of medroxyprogesterone acetate combined with a levonorgestrel-releasing intrauterine contraceptive system after laparoscopic surgery for moderate and severe endometriosis can effectively regulate serum levels of sex hormone and vascular endothelial growth factor, decrease endometriosis recurrence rate and is highly safe. This method is worthy of clinical promotion.

Inhibitory Effect of Duanteng Yimu Decoction on Pannus Formation in Mice with Collagen-induced Arthritis Based on VEGF Pathway / 中国实验方剂学杂志

Objective:To investigate the mechanism of Duanteng Yimu decoction （DTYM） in the inhibition of pannus formation in collagen-induced arthritis （CIA） mice. Method:Twenty-four SPF-grade DBA/1 male mice were randomly divided into the following four groups： a blank group （NC group）， a model group （CIA group）， a methotrexate group （MTX group）， and a DTYM group， with six mice in each group. The mice， except for those in the NC group， were modeled. From the second immunization， the medium， MTX （1 mg·kg^-1）， and DTYM （15.4 g·kg^-1） were administered at an equal volume by gavage for 35 days. Mice were observed for general condition and the arthritis index. The knee and ankle joints were scanned by microcomputed tomography （micro CT）. Hematoxylin-eosin （HE） and safranin O/fast green staining were performed to observe pathological changes. Immunohistochemistry was performed to detect the expression of platelet/endothelial cell adhesion molecule-1 （CD31）， vascular endothelial growth factor-<italic>α</italic> （VEGF-<italic>α</italic>）， vascular endothelial growth factor receptor 2 （VEGFR2）， and phosphorylated（p）-VEGFR2. Result:Compared with the NC group， the CIA group showed red and swollen ankle joints， increased arthritis index scores （<italic>P</italic><0.05， <italic>P</italic><0.01）， manifest injury in the knee and ankle joints， reduced cartilage thickness， elevated Micro CT bone destruction scores of knee and ankle joints （<italic>P</italic><0.01）， and up-regulated absorbance values of synovial CD31， VEGF-<italic>α</italic>， VEGFR2， and p-VEGFR2 （<italic>P</italic><0.01）. Compared with the CIA group， the DTYM group showed relieved ankle joint redness and swelling， reduced arthritis index scores of mice three weeks after administration （<italic>P</italic><0.05， <italic>P</italic><0.01）， intact joint surfaces of the knee and ankle joints， thickened cartilage， declining Micro CT bone destruction scores in both the knee and ankle joints （<italic>P</italic><0.05， <italic>P</italic><0.01）， and lowered absorbance values of CD31， VEGF-<italic>α</italic>， VEGFR2， and p-VEGFR2 in the synovium （<italic>P</italic><0.01）. Conclusion:DTYM can inhibit the pannus formation in CIA mice presumedly by regulating the VEGF pathway.

Risk factors of perivalvular leakage after transcatheter aortic valve replacement with Venus-A valve / 中华心血管病杂志

Objective: To investigate the risk factors of moderate or severe perivalvular leakage (PVL) after transcatheter aortic valve replacement (TAVR) with Veneus-A valve. Methods: This study was a single-center case-control study. The clinical data of patients with severe aortic stenosis, who underwent TAVR in the Department of Cardiology of Second Affiliated Hospital of Army Medical University from October 2017 to January 2021, were analyzed. According to the circumferential extent of prosthetic valve paravalvular regurgitation measured by transthoracic echocardiography before discharge (patients who died in hospital were referred to transesophageal echocardiography results after valve implanted), the patients were divided into moderate or severe PVL group and mild or non-PVL group. The clinical features, CT scan and analysis results of aortic root were compared between the two groups. Multivariate logistic regression analysis was used to identify the independent risk factors of postoperative moderate or severe PVL, and receiver operating characteristic (ROC) curve was used to explore the predictive value of related factors. Results: Eighty-two patients (mean age: (70.9±6.5) years, 46 males) were included in the analysis, there were 16 patients in the moderate or severe PVL group and 66 patients in the mild or non-PVL group. The proportion of male gender, depth of valve implantation, size of valve annulus and left ventricular outflow tract (LVOT), and coverage index of LVOT were significantly higher in moderate or severe PVL group than those in mild or non-PVL group (Pall<0.05). As there was a strong collinearity among the valve annular short diameter, LVOT short diameter and LVOT coverage index (partial correlation coefficient R 0.251-0.779, P<0.05), these parameters were not entered in regression model. Multivariate logistic regression analysis showed that valve implantation depth(OR=1.239,95%CI 1.036-1.442,P=0.023), aortic angulation(OR=1.128, 95%CI 1.044-1.312,P=0.038)and LVOT tract coverage index (OR=1.123, 95%CI1.003-1.315, P=0.032) were independent risk factors for moderate or severe PVL after TAVR. The ROC curve showed that the valve implantation depth could predict the occurrence of moderate or severe PVL after TAVR (area under ROC curve (AUC)=0.697, 95%CI 0.554-0.851, P=0.039). Conclusion: Among patients with severe aortic stenosis who undergo TAVR with Venus-A valve, the implantation depth, aortic angulation and LVOT coverage index are independent risk factors of moderate/severe PVL after TAVR, among which valve implantation depth could be used to predict the occurrence of moderate/severe PVL after TAVR.

Expression of LncRNA-MALAT1 in Peripheral Blood of Patients with Acute Myeloid Leukemia Sepsis and Its Clinical Significance / 中国实验血液学杂志

OBJECTIVE@#To analyze the expression of lncRNA-MALAT1 in peripheral blood of patients with acute myeloid leukemia (AML) sepsis and explore its clinical significance.@*METHODS@#From March 2018 to March 2019, 95 confirmed AML patients including 43 sepsis infected cases and 52 uninfected cases were selected for treatment in the Department of Oncology and Hematology, The First People's Hospital of Longquanyi District. Their peripheral blood samples were taken as study samples, and the blood samples from 50 healthy people were used as control. RT-qPCR was used to detect lncRNA-MALAT1 expression level in samples from healthy group, uninfected group, and sepsis group. The correlation between lncRNA-MALAT1 expression level and clinical characteristics and prognosis of AML patients with sepsis were analyzed.@*RESULTS@#The expression level of lncRNA-MALAT1 in the sepsis group was significantly up-regulated compared with the healthy group and uninfected group (P0.05). In AML patients with sepsis, the expression of lncRNA-MALAT1 was associated with clinical characteristics such as NCCN risk classification, white blood cell count, hemoglobin and so on. The overall survival rate of high lncRNA-MALAT1 expression group was significantly lower than that of low expression group (χ@*CONCLUSION@#The up-regulated expression of lncRNA-MALAT1 is closely related to the clinical characteristics and survival rate, and is an independent prognostic factor for AML sepsis patients. LncRNA-MALAT1 is expected to become a new diagnostic marker and therapeutic target for AML sepsis.

Current status and changes of disease burden of cardio-cerebrovascular diseases in 1990 and 2016 for Beijing people / 中华心血管病杂志

Objective: To investigate the current status and changes of disease burden of cardio-cerebrovascular diseases in 1990 and 2016 for Beijing people. Methods: Using the results of the Global Burden of Diseases Study 2016 (GBD 2016) to describe deaths status and disease burden of cardio-cerebrovascular diseases in Beijing. The measurement index included the total deaths, years of life lost due to premature mortality (YLL), years lived with disability (YLD), and disability-adjusted years (DALY). Using the average world population from 2000 to 2025 as standard population to calculate the age-standardized mortality rate, DALY rate, YLL rate and YLD rate. Results: The age-standardized mortality rate of cardio-cerebrovascular diseases was 209.24 per 100 000. In 2016, DALY, YLL and YLD of cardio-cerebrovascular was 875.6, 733.6 and 142.0 thousand person-years, respectively, which has increased by 58.05%, 44.24% and 213.47%, respectively, than that in 1990. The age-standardized DALY rate and age-standardized YLL rate of cardio-cerebrovascular diseases in 2016 was 3 552.24 and 2 988.01 per 100 000 which has decreased by 47.90% and 52.43%, respectively, than that in 1990. The age-standardized YLD rate of cardio-cerebrovascular diseases in 2016 was 564.23 per 100 000 which increased by 5.10% than that in 1990. In 2016, the total death of cerebrovascular disease and ischemic heart disease was 17.6 thousand and 23.7 thousand, respectively. DALY was 396.3 and 393.6 thousand person-years in 2016, while 330.2 and 162.7 thousand person-years in 1990, which has increased by 20.02% and 141.92%, respectively. Conclusions: The disease burden of cardio-cerebrovascular disease is serious, especially the burden of cerebrovascular disease and ischemic heart disease. The disability burden of cerebrovascular disease is serious. The disease burden of ischemic heart disease has multiplied.

Functional roles of sodium-calcium exchange in autorhythmicity and action potential of murine fetal cardiomyocytes at early developmental stage / 生理学报

The aim of the present paper was to study the role of sodium calcium exchanger (NCX) in the generation of action potentials (APs) in cardiomyocytes during early developmental stage (EDS). The precisely dated embryonic hearts of C57 mice were dissected and enzymatically dissociated to single cells. The changes of APs were recorded by whole-cell patch-clamp technique before and after administration of NCX specific blockers KB-R7943 (5 μmol/L) and SEA0400 (1 μmol/L). The results showed that, both KB-R7943 and SEA0400 had potent negative chronotropic effects on APs of pacemaker-like cells, while such effects were only observed in some ventricular-like cardiomyocytes. The negative chronotropic effect of KB-R7943 on ventricular-like cardiomyocytes was accompanied by shortening of AP duration (APD), whereas such an effect of SEA0400 was paralleled by decrease in velocity of diastolic depolarization (Vdd). From embryonic day 9.5 (E9.5) to E10.5, the negative chronotropic effects of KB-R7943 and SEA0400 on ventricular-like APs of embryonic cardiomyocytes gradually disappeared. These results suggest that, in the short-term development of early embryo, the function of NCX may experience developmental changes as evidenced by different roles of NCX in autorhythmicity and APs generation, indicating that NCX function varies with different conditions of cardiomyocytes.

Prognostic value of red cell distribution width in maintenance hemodialysis patients / 中华肾脏病杂志

Objective To investigate the relationship of red cell distribution width (RDW) with all-cause mortality and cardiovascular disease (CVD) mortality in patients undergoing maintenance hemodialysis (MHD).Methods A retrospective analysis was performed in patients who initiated MHD from January 2008 to September 2017 in the hemodialysis center of the Second Affiliated Hospital of Soochow University.Basic data on demographic,dialysis and laboratory were collected,and echocardiography indicators and clinical outcomes were recorded.Patients were divided into four groups according to the quartile of RDW level.Kaplan-Meier survival analysis was used to compare the difference of survival rate among the groups.Cox regression analysis was used to analyze the risk factors of all-cause and CVD-related mortality,and predictive value of RDW for all-cause and CVD-related death in hemodialysis patients.Results A total of 268 MHD patients were enrolled in this study with age of (60.9± 15.8) years and dialysis duration of (58.1±9.1) months,including 159 males (59.3％).Kaplan-Meier survival analysis showed that the 1-year overall survival rates of Q1 group (RDW≤ 13.8％,n=61),Q2 group (RDW 13.9％-14.6％,n=66),Q3 group (RDW 14.7％-15.6％,n=73)and Q4 group (RDW≥15.7％,n=68) were 96.8％,95.1％,93.1％ and 85.7％ respectively;3-year overall survival rates were 88.5％,87.5％,59.2％ and 51.8％ respectively;5-year overall survival rates were 71.5％,65.4％,33.6％ and 17.7％ respectively;The difference between the groups was statistically significant (all P ＜ 0.01).The 1-year CVD survival rates were 98.4％,96.6％,95.8％ and 92.4％ respectively;3-year CVD survival rates were 94.8％,92.5％,84.4％ and 70.4％ respectively;5-year CVD survival rates were 86.9％,81.3％,65.6％ and 51.3％ respectively;The difference between the groups was statistically significant (all P ＜ 0.01).Multivariate Cox regression analysis showed that RDW≥15.7％ was an independent risk factor for all-cause and CVD-related mortality in MHD patients.The risk of all-cause mortality in Q4 group was 3.098 times higher than that in Q 1 group (95％ CI 1.072-8.950,P=0.037) and the risk of CVD-related mortality was 2.661 times (95％ CI 1.111-8.342,P=0.048).Receiver operating characteristic curve (ROC) showed that RDW=14.85％ was the best cut-off point for predicting the all-cause mortality in HD patients (P ＜ 0.01),RDW=15.45％was the best cut-off point for predicting the cardiovascular disease mortality (P ＜ 0.01),and RDW=14.45％ had a higher 5-year survival rate (P ＜ 0.01).Conclusion RDW can independently predict all-cause and CVD-related mortality risk in hemodialysis patients,and it has important value for prognosis.

Mechanism of Tripterygium hypoglaucum Radix-Leonurus japonicus Herba for Treating Rheumatoid Arthritis Based on Network Pharmacology / 中国实验方剂学杂志

Objective:Computer network pharmacology technology was used to screen the main active ingredients of Tripterygium hypoglaucum radix-Leonurus japonicus herba for the treatment of rheumatoid arthritis(RA), predict the targets of the active ingredients, establish a pharmaceutical ingredient-active ingredient-target network, and further explore the potential mechanism of Tripterygium hypoglaucum radix-Leonurus japonicus herba for the treatment of RA. Method:RA disease targets were collected through DisGeNET, TTD, and Drugbank databases, the potential active components of Tripterygium hypoglaucum radix and Leonurus japonicus herba and their corresponding targets were obtained from the Chinese Medicine System Pharmacology Analysis Platform (TCMSP); common targets for drugs and diseases were screened by using the ImageGP platform; a common target interaction (PPI) network model was constructed by using the String database, a "drug-active ingredient-key target" network was constructed by using Cytoscape software, a protein interaction network was constructed by using the String database, gene function (GO) analysis and pathway enrichment analysis based on the Kyoto Gene and Genomic Encyclopedia (KEGG) were performed by using the ClueGO plug-in. Result:Through screening, 9 active pharmaceutical ingredients were obtained, involving a total of 235 targets, and 7 active ingredients were related to the disease targets. 24 common targets for Tripterygium hypoglaucum radix Leonurus japonicus herba-disease were obtained. The common targets were mainly enriched in 278 biological processes and 141 signaling pathways to play a role in the treatment of RA. Conclusion:The therapeutic effect of Tripterygium hypoglaucum radix Leonurus japonicus herba on RA reflects the characteristics of multi-component-multi-target-multi-channel of traditional Chinese medicine, and provides a scientific basis for explaining its mechanism and clinical application of RA.

Mechanism of Wulingsan in Treatment of Rheumatoid Arthritis Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To study the mechanism of Wulingsan (WLS) in the treatment of rheumatoid arthritis (RA) by network pharmacology. Method:The active components of WLS were screened on traditional Chinese medicine systems pharmacology(TCMSP) platform, and the targets were predicted in DragBank database. The "component-target" network was constructed by Cytoscape 3.2.1 software. Disease targets were searched in TTD, DrugBank and DisGenet databases. The Venn diagram was built to extract the target of WLS in the treatment of RA, and the gene oesthetics(GO) function annotation and Kyoto Encyclopedin of Genes and Genomes(KEGG) signal pathway enrichment analysis were performed by cluego plugin. The TCM-component-target-pathway network of WLS was constructed, and the network feature analysis was made by Network Analyzer. Result:Totally 52 components and 297 potential targets in WLS and 1 845 targets relating to RA were excavated, and 49 common targets of WLS-RA were obtained. The common targets were mainly enriched in 322 biological processes and 31 signaling pathways. Conclusion:WLS may regulate targets, such as prostaglandin epoxide synthase 2 (PTGS2), transforming growth factor-β1 (TGF-β1), cysteine aspartate protein-3 (Caspase-3), transcription factor p65 (RELA), progesterone receptor (PGR), and adjust cancer-related pathways, tumor necrosis factor(TNF) signaling pathways, interleukin-17(IL-17) signaling pathways, nuclear factor-κB(NF-κB) signaling pathways, Th17 cell differentiation, so as to inhibit the inflammatory response, regulate immune function and adjust apoptosis to treat rheumatoid arthritis.

Study of the effect of polysaccharides from Yupingfeng on keratinocytes / 药学实践杂志

Objective To study the immunomodulatory effect of Yupingfeng polysaccharides on keratinocytes in vitro.Methods The effects of Yupingfeng polysaccharides on the expression of various inflammatory factors in the activated keratinocytes were detected by the Real-time PCR method.The mRNA and protein expression levels of Filaggrin were detected by Real-time PCR and Elisa respectively.The western bolt assay was used to detect the regulation of NF-κB signaling pathway by polysaccharides.Results Yupingfeng polysaccharides inhibited the secretion of inflammatory factors in the activated keratinocytes, promoted the expression of Filaggrin and exhibited significant inhibitory effect on the NF-κB signaling pathway, which plays an important role in the inflammation and immune response.Conclusion Yupingfeng polysaccharides had an immune regulation effect on skin keratinocytes in vitro and alleviated the development of local inflammation.These results lay a theoretical foundation for the clinical application of Yupingfeng prescription.

The therapeutic effect of pelvic floor muscle exercise on urinary incontinence after radical prostatectomy: a meta-analysis / 亚洲男科学杂志(英文版)

Pelvic floor muscle exercise (PFME) is the most common conservative management for urinary incontinence (UI) after radical prostatectomy (RP). However, whether the PFME guided by a therapist (G-PFME) can contribute to the recovery of urinary continence for patients after RP is still controversial. We performed this meta-analysis to investigate the effectiveness of G-PFME on UI after RP and to explore whether the additional preoperative G-PFME is superior to postoperative G-PFME alone. Literature search was conducted on Cochrane Library, Embase, Web of Science, and PubMed, to obtain all relevant randomized controlled trials published before March 1, 2018. Outcome data were pooled and analyzed with Review Manager 5.3 to compare the continence rates of G-PFME with control and to compare additional preoperative G-PFME with postoperative G-PFME. Twenty-two articles with 2647 patients were included. The continence rates of G-PFME were all superior to control at different follow-up time points, with the odds ratio (OR) (95% confidence interval [CI]) of 2.79 (1.53-5.07), 2.80 (1.87-4.19), 2.93 (1.19-7.22), 4.11 (2.24-7.55), and 2.41 (1.33-4.36) at 1 month, 3 months, 4 months, 6 months, and 12 months after surgery, respectively. However, there was no difference between additional preoperative G-PFME and postoperative G-PFME, with the OR (95% CI) of 1.70 (0.56-5.11) and 1.35 (0.41-4.40) at 1 month and 3 months after RP, respectively. G-PFME could improve the recovery of urinary continence at both early and long-term stages. Starting the PFME preoperatively might not produce extra benefits for patients at early stage, compared with postoperative PFME.