PurposeTo evaluate the effect of right ventricular septum (RVS) and right ventricular apex (RVA) pacing on the left atrial systolic function in patients with atrioventricular block by using real-time three-dimensional echocardiography (RT-3DE).Materials and Methods Fifty-one patients with atrioventricular block who were candidates for implanted atrioventricular sequential pacemaker were randomly divided into RVS group (n=31) and RVA group (n=20). The minimum left atrium volume (LAVmin), maximum left atrium volume (LAVmax), and left atrium volume before contraction (LAVprep) were measured by RT-3DE at pre-operation, the 1st month, 3rd month, 6th month, and 12th month after pacemaker implantation. Accordingly, the left atrial total ejection fraction (LATEF) and the left atrial active ejection fraction (LAAEF) were calculated.Results The LAVmin at the 3rd month, 6th month, 12th month after implantation were significantly lower than that at the 1st month and pre-operation in both groups (RVA group:t=2.97 and 2.74,P<0.05; RVS group:t=3.24 and 2.86,P<0.05). LAVprep at the 6th month, 12th month in RVA group, and LAVprep at the 3rd month, 6th month, 12th month in RVS group reduced when compared with that of pre-operation (RVA group:t=3.20,P<0.05; RVS group:t=2.71,P<0.05). LATEF and LAAEF in both groups at the 3rd month, 6th month, 12th month increased when compared with that of pre-operation (RVA group:t=2.87 and 9.68,P<0.05; RVS group:t=3.56 and 8.22,P<0.05). The LATEF and LAAEF in RVS group at the 6th month and 12th month after implantation were significantly larger than that in RVA group at the same time (t=2.90, 5.22, 3.03 and 3.55, P<0.05).Conclusion Atrioventricular sequential pacing is helpful to recovering the left atrial systolic function in patients with atrioventricular block. Compared with RVA pacing, RVS pacing is able to increase LATEF and LAAEF more greatly.

Objective To investigate the effect of platelet-derived growth factor-D (PDGF-D) on the prostate cancer cells migration and its possible mechanism. Methods The expressions of PDGF-D in LNCaP and PC-3 cells were detected with western blot.PDGF-D siRNA was synthesized according to mRNA sequence of PDGF-D gene and was transfected into PC-3 cell.The cells were treated with PDGF-D and PDGF-D siRNA,the cell migration was examined by Boyden chamber migration assay.The expression changes of VEGF and MMP-9 mRNA were detected by RT-PCR. Results The results of western blot indicated that the PDGF-D protein expression level was lower in LNCaP cells (29.47 ± 1.68) than that in PC-3 cells (63.43 ±2.10),(P ＜ 0.05).PDGF-D siRNA could down-regulate the PDGF-D protein expression in the transfected group (35.19 ± 1.51).The exogenous PDGF-D could promote migration of LNCaP and PC-3cells,and up-regulate the expression of VEGF,MMP-9 mRNA in PC-3 cells (P ＜ 0.05,compared with control group).PDGF-D siRNA inhibited PC-3 cells' migration and decreased the level of VEGF,MMP-9mRNA expression (0.72 ± 0.09 vs 0.43 ± 0.18,0.65 ±0.07 vs 0.22 ± 0.08) (P ＜ 0.05). Conclusion PDGF-D is involved in the promotion of prostate cancer invasion and angiogenesis.

Objective To evaluate the efficacy and safety of triethanolamine cream in the treatment of skin ulcer. MethodsA multicenter,single-blind,randomized,positive-control study was conducted.One-hundred and twenty patients aging 18-65 years with skin ulcer were randomly classified into the test and control group at a ratio of 2 ∶ 1 to be treated with triethanolamine cream and recombinant bovine basic fibroblast growth factor gel respectively for 4 weeks.The healing rate of ulcer,granulation tissue production rate and epithelialization rate were calculated.Results After the beginning of treatment,the condition of all patients was improved with time.In total,76 out of 80 triethanolamine-treated patients and 38 out of 40 basic fibroblast growth factor gel-treated patients completed the 4-week trial.Significant differences were observed in the healing rate of ulcer,epithelialization rate and granulation tissue production rate between the test and control group (71.05％ vs.34.21％,P =0.0002; 85％ vs.50％,P =0.0001; 66.25％ vs.37.5％,P =0.0035).No adverse events occurred in any of the patients.Conclusions Triethanolamine cream seems superior to recombinant bovine basic fibroblast growth factor gel with regard to the healing rate of ulcer,epithelialization rate and granulation tissue production rate,and may be a promising drug for the treatment of skin ulcer.

To investigate the correlation between methylation and expression of multidrug resistance (mdr1) gene, restriction endonuclease HpaII combined with competitive PCR technique was used to quantitatively detect the methylation status of two CCGG sites located at -110 and -50 bp (region I and II) up to the transcription start site in mdr1 promoter in 54 AL and 9 MM patients. Semi-quantitative RT-PCR was used to detect the expression level of mdr1 gene. The results showed that inverse correlation between methylation rate of either region or total methylation rate and expression of mdr1 gene was observed. The correlation in the region I (r = -0.64) was closer than that in the region II (r = -0.4). High expression rate of mdr1 ascended significantly in low methylation group (n = 36) (P < 0.001). In comparison with chemotherapy sensitive group (n = 8), the methylation rate in refractory AL patients (n = 16) was lower (P = 0.05) in the region I, P < 0.05 in the region II and total regions. Comparing with the untreated patients (n = 36), the methylation rate in the region I and total methylation rate were lower in the patients with chemotherapy (n = 14) (P < 0.05). The methylation rate in the region II was also decreased after chemotherapy, however, no statistical significance was shown (P > 0.05). Increased mdr1 expression level accompanying with decreased methylation rate after chemotherapy was found, although no significant difference was shown (P = 0.06). It is concluded that the expression level of mdr1 gene was associated with the methylation status of CCGG in -110 and -50 bp upstream to the transcription start site, especially the -110 site. In both the patients treated with chemotherapy and the refractory patients, the methylation level of mdr1 gene decreased relatively. The rising expression of mdr1 gene after chemotherapy was associated with the decrease of methylation level.
DNA Methylation ; Genes, MDR ; Hematologic Neoplasms ; drug therapy ; genetics ; Humans ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo study the protective effect of ischemic preconditioning (I-pre) and ischemic postconditioning (I-post) against ischemia/reperfusion (I/R) injury in rat's liver.

METHODSUsing rat model of hepatic segmental I/R injury, rats were divided into 5 groups: Group A (sham group), Group B (I/R injury), Group C (I-pre group), Group D (I-post group) and Group E (combined treatment of I-pre and I-post). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and myeloperoxidase (MPO) in hepatic tissues were determined, respectively. In addition, 7 days'survival of Groups B, C, D and E were evaluated.

RESULTSCompared with Group B, Groups C, D and E exhibited significantly decreased ALT and AST release, minimized tissue injury, suppressed values of MDA and MPO, increased activities of SOD, GSH-Px and GSH (P less than 0.05), as well as improved animal survival. The differences among Groups C, D and E were not statistically significant.

CONCLUSIONSI-pre, I-post and combined therapy of I-pre and I-post have protective effect against hepatic I/R injury, which is correlated with its function of reducing the production of reactive oxygen species, maintaining the activities of antioxidant systems and suppressing neutrophils recruitment. No additive effect can be obtained in Group E.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Ischemic Preconditioning ; Liver Diseases ; therapy ; Male ; Rats ; Reperfusion Injury ; prevention & control ; therapy

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

To investigate the relationship between the LNK(SH2B3) gene single nucleotide polymorphism and risk of acute leukemia (AL) in Chinese population.

METHODSThe bone marrow and peripheral blood samples from 31 cases of acute lymphoblastic leukemia, 70 cases of acute myeloid leukemia and 130 healthy persons as the controls were collected. Genotype of LNK SNP Rs3184504(c.784T>C) and Rs78894077(c.724C>T) were determined by PCR-RFLP, and were confirmed by gel electrophoresis and sequencing. The NB4, THP-1 and Raji leukemia cell line models were cultured, the leukemia cell line LNK Rs3184504 and Rs78894077 polymorphism were detected by using direct sequencing.

RESULTSThe CC genotype frequencies of Rs3184504 SNP were higher in ALL and AML patients than those in control (P<0.01), but there was no different between the groups in AML and ALL. The frequency of LNK gene Rs3184504 C allele was higher in AL as compared with control (P<0.01). The LNK gene Rs78894077 locus genotype distribution was not significantly different between the AL and the normal control group (P>0.05). Both Rs3184504 and Rs78894077 sites were detected as CC genotype in NB4, THP-1 and Raji cells.

CONCLUSIONThe persons carrying C allele of LNK gene Rs3184504 are more prone to develop acute leukemia.

The objective of this study was to investigate the expression profile of the myozenin2 (MYOZ2) gene and elucidate its effect on adipogenic differentiation of C3H10T1 / 2 cells and its possible mechanism∙ The longissimus dorsi‚ subcutaneous fat and liver tissue was collected from 180-day-old Mashen pigs‚ 60-day-old ICR mice‚ 35-day-old Ross broiler and 12-month-old Small tail han sheep‚ and the expression profile of the MYOZ2 gene mRNA was detected∙ The results showed that the MYOZ2 gene has similar patterns of tissue expression in examined species‚ with the highest expression level in longissimus dorsi‚ and a small amount of expression in the subcutaneous fat and liver tissue∙ After the MYOZ2 gene was silenced in C3H10T1 / 2 cells‚ qRT-PCR results showed that the expression levels of key adipogenic genes PPARγ and FABP4 were significantly down-regulated compared with the control group (P < 0∙ 01) ; Western Blotting results showed that the PPARγ protein content was significantly decreased (P < 0∙ 05) ; Oil red O staining showed that the number of lipid droplets and the content of triglyceride were significantly decreased after silencing MYOZ2 (P < 0∙ 05) ∙ The expression of fatty acid metabolism related genes SCD‚ FASN‚ SREBP1‚ NR1H3‚ DGAT1‚ PNPLA2‚ HSL‚ CES1‚ CPT1 after MYOZ2 silencing were detected by qRT-PCR∙ The results showed that SCD‚ FASN‚ SREBP1‚ PNPLA2 and HSL were significantly down-regulated (P < 0∙ 01) ‚ NR1H3 was significantly reduced (P < 0∙ 05) ‚ DGAT1 expression was down-regulated but the difference was not significant‚ CES1 and CPT1 were significantly up-regulated (P < 0∙ 05) ∙ The STRING database was used to construct a MYOZ2-related protein interaction network map‚ and it was found that MYOZ2 may affect the adipogenic differentiation through the interaction of titin-cap (TCAP) and PPARγ∙ After silencing TCAP‚ qRT-PCR results showed that compared with the control group‚ the expression of key adipogenic genes PPARγ and FABP4 were significantly up-regulated (P < 0∙ 01) ; Western Blotting results showed that PPARγ protein was significantly increased (P< 0∙ 05) ; Oil red O staining showed that the number of lipid droplets and the content of triglyceride were significantly increased after TCAP silencing (P < 0∙ 05) ∙ qRT-PCR was used to detect the expression of TCAP after silencing MYOZ2‚ and the results showed that the expression of TCAP was significantly increased (P<0∙ 01) ∙ In summary‚ MYOZ2 was highly expressed in longissimus dorsi and lower expressed in subcutaneous fat and liver tissues∙ In addition‚ MYOZ2 may regulate the expression of key adipogenic genes PPARγ and FABP4 through the interaction of MYOZ2-TCAP -PPARγ‚ and to further regulate the expression of fatty acid metabolism related genes SCD‚ FASN‚ SREBP1‚ NR1H3‚ DGAT1‚ PNPLA2‚ HSL‚ CES1 and CPT1‚ thus playing an important role in the process of adipogenic differentiation∙

OBJECTIVE: Epstein-Barr virus associated gastric cancer (EBVaGC) is different from the traditional gastric cancer (Epstein-Barr virus non-associated gastric cancer, EBVnGC), and has unique clinicopathological features. This study investigated the largest single center cancer series so as to establish the clinicopathological and molecular characteristics of EBVaGC in China. METHODS: A retrospective analysis was conducted on EBVaGC and EBVnGC patients diagnosed at Peking University Cancer Hospital from 2003 to 2018 by comparing their clinicopathological features and prognosis. The gastric cancer (GC) dataset of public database was analyzed to obtain differentially expressed genes. The expression of important genes and their association with prognosis of GC were verified in GC tissues from our hospital. RESULTS: In this study, 3 241 GC patients were included, and a total of 163 EBVaGC (5.0%) patients were identified. Compared with EBVnGC, EBVaGC was higher in male and younger patients, and positively associated with remnant GC, poorly differentiated adenocarcinoma, and mixed type GC. EBVaGC was inversely related to lymph node metastasis. The 5-year survival rate of EBVnGC and EBVaGC was 59.6% and 63.2% respectively (P<0.05). In order to explore molecular features of EBVaGC, the Cancer Genome Atlas (TCGA) dataset was analyzed (n=240), and 7 404 significant differentially expressed genes were obtained, involving cell proliferation, apoptosis, invasion and metastasis. The down-regulated invasion/metastasis gene SALL4 and the up-regulated immune checkpoint gene PD-L1 were important molecular features of EBVaGC. Validation of these two genes in large GC series showed that the majority of the EBVaGC was SALL4 negative (1/92, 1.1%, lower than EBVnGC, 303/1 727, 17.5%), and that PD-L1 was mostly positive in EBVaGC (81/110, 73.6%, higher than EBVnGC, 649/2 350, 27.6%). GC patients with SALL4 negative and PD-L1 positive were often associated with better prognosis. CONCLUSION EBVaGC is a unique subtype of GC with less metastasis and a good prognosis. It also has a distinct molecular background. The down-regulation of invasion/metastasis gene SALL4 and up-regulation of immune checkpoint gene PD-L1 are important molecular features.
China ; Epstein-Barr Virus Infections/complications* ; Female ; Herpesvirus 4, Human ; Humans ; Male ; Retrospective Studies ; Stomach Neoplasms/etiology*

Background: Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study. Methods: TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54). Results: Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning. Conclusions: Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China. Trial Registration ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1.
China ; Crotonates ; administration & dosage ; adverse effects ; therapeutic use ; Double-Blind Method ; Drug Administration Schedule ; Humans ; Immunosuppressive Agents ; administration & dosage ; adverse effects ; therapeutic use ; Multicenter Studies as Topic ; Multiple Sclerosis ; drug therapy ; metabolism ; Proportional Hazards Models ; Toluidines ; administration & dosage ; adverse effects ; therapeutic use