Role of sirtuin 5 in cardiovascular diseases / 中国药理学通报

Cardiovascular diseases ( CVDs ) are the leading cause of death worldwide and pose a serious threat to human health. Silent information regulator 5 ( SIRT5 ) , which is widely distributed in cardiac myocytes, vascular smooth muscle cells and endothelial cells,as a novel deacylation-modifying enzyme,plays an important role in CVDs through deacetylation, desuccinylation and demalonylation. This review summarizes the pathophysiolog-ical mechanism of SIRT5 from the aspects of energy metabolism, regulation of inflammatory response and oxidative stress, apart from the role of SIRT5 in CVDs such as myocardial infarction, myocardial hypertrophy, arrhythmia, atherosclerosis and heart failure. This review also figures out the current research progress of SIRT5 -related inhibitors and agonists, so as to provide strategies for targeting SIRT5 to prevent and treat CVDs.

Development and validation of a prognostic prediction model for patients with stage Ⅰ to Ⅲ colon cancer incorporating high-risk pathological features / 中华外科杂志

Objective: To examine a predictive model that incorporating high risk pathological factors for the prognosis of stage Ⅰ to Ⅲ colon cancer. Methods: This study retrospectively collected clinicopathological information and survival outcomes of stage Ⅰ~Ⅲ colon cancer patients who underwent curative surgery in 7 tertiary hospitals in China from January 1, 2016 to December 31, 2017. A total of 1 650 patients were enrolled, aged (M(IQR)) 62 (18) years (range: 14 to 100). There were 963 males and 687 females. The median follow-up period was 51 months. The Cox proportional hazardous regression model was utilized to select high-risk pathological factors, establish the nomogram and scoring system. The Bootstrap resampling method was utilized for internal validation of the model, the concordance index (C-index) was used to assess discrimination and calibration curves were presented to assess model calibration. The Kaplan-Meier method was used to plot survival curves after risk grouping, and Cox regression was used to compare disease-free survival between subgroups. Results: Age (HR=1.020, 95%CI: 1.008 to 1.033, P=0.001), T stage (T3:HR=1.995,95%CI:1.062 to 3.750,P=0.032;T4:HR=4.196, 95%CI: 2.188 to 8.045, P<0.01), N stage (N1: HR=1.834, 95%CI: 1.307 to 2.574, P<0.01; N2: HR=3.970, 95%CI: 2.724 to 5.787, P<0.01) and number of lymph nodes examined (≥36: HR=0.438, 95%CI: 0.242 to 0.790, P=0.006) were independently associated with disease-free survival. The C-index of the scoring model (model 1) based on age, T stage, N stage, and dichotomous variables of the lymph nodes examined (<12 and ≥12) was 0.723, and the C-index of the scoring model (model 2) based on age, T stage, N stage, and multi-categorical variables of the lymph nodes examined (<12, 12 to <24, 24 to <36, and ≥36) was 0.726. A scoring system was established based on age, T stage, N stage, and multi-categorical variables of lymph nodes examined, the 3-year DFS of the low-risk (≤1), middle-risk (2 to 4) and high-risk (≥5) group were 96.3% (n=711), 89.0% (n=626) and 71.4% (n=313), respectively. Statistically significant difference was observed among groups (P<0.01). Conclusions: The number of lymph nodes examined was an independent prognostic factor for disease-free survival after curative surgery in patients with stage Ⅰ to Ⅲ colon cancer. Incorporating the number of lymph nodes examined as a multi-categorical variable into the T and N staging system could improve prognostic predictive validity.

Efficacy of transanal hand-sewn reinforcement in low rectal stapled anastomosis in preventing anastomotic leak after transanal total mesorectal excision / 中华胃肠外科杂志

Objective: To explore the efficacy and feasibility of transanal hand-sewn reinforcement of low stapled anastomosis in preventing anastomotic leak after transanal total mesorectal excision (taTME). Methods: A descriptive cohort study was conducted. Clinical data of 51 patients with rectal cancer who underwent taTME with transanal hand-sewn reinforcement of low stapled anastomosis at Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2020 were retrospectively collected. Inclusion criteria: (1) age >18 years old; (2) rectal cancer confirmed by preoperative pathology; (3) distance from tumor to anal verge ≤ 8 cm according to pelvic MR; (4) the lesion was evaluated to be resectable before operation; (5) with or without neoadjuvant chemotherapy and radiotherapy; (6) taTME, end-to-end stapled anastomosis, and reinforcement in the anastomosis with absorbable thread intermittently were performed, and the distance between anastomosis and anal verge was ≤ 5 cm. Exclusion criteria: (1) previous history of colorectal cancer surgery; (2) emergency surgery due to intestinal obstruction, bleeding or perforation; (3) patients with local recurrence or distant metastasis; (4) the period of postoperative follow-up less than 3 months. The procedure of transanal hand-sewn reinforcement was as follows: firstly, no sign of bleeding was confirmed after checking the anastomosis. Then, the anastomosis was reinforced by suturing the muscle layer of rectum intermittently in a figure-of-eight manner using 3-0 single Vicryl. The entry site of the next suture was close next to the exit site of the last one. Any weak point of the anastomosis could also be reinforced according to the specimen from the circular stapler. The primary outcome were the incidence of anastomotic leak, methods of the secondary operation, anastomotic infection, anastomotic stricture, and conditions of Intraoperative and postoperative. Results: All the 51 enrolled patients completed surgery successfully without any conversion to open surgery. The median operative time was 169 (109-337) minutes, and the median intraoperative blood loss was 50 (10-600) ml. The median postoperative hospital stay was 8 (5-16) days. The mssorectum was complete and distal resection margin was negative in all patients. Postive circumferential resection margin was observed in 1 patients (2.0%). Twelve (23.5%) patients underwent prophylactic ileostomy. One patient developed anastomosis stricture which was cured by digital dilatation of the anastomosis. ISREC grade C anastomotic leak was observed in 3 (5.9%) male patients, of whom 2 cases did not received prophylactic ileostomy during the operation, and were cured by a second operation with the ileostomy and anastomotic repair. The other one healed by transanal repair of the anastomosis and anti-infection therapy. One (2.0%) patient suffered from perianal infection and healed by sitz bath and anti-infection therapy. No death was reported within 30 days after operation. Conclusion: Transanal hand-sewn reinforcement in low rectal stapled anastomosis in preventing anastomotic leak after taTME is safe and feasible.

Research progress and future development prospect of transanal total mesorectal excision / 中华胃肠外科杂志

Transanal total mesorectal excision (taTME) is one of the hotspots in colorectal surgery in recent years. Although most studies confirm that taTME is safe and feasible, some studies still showed that the morbidity of complication and local recurrence rate of taTME were higher than traditional laparoscopic surgery. This article reviews and analyzes the short-term and long-term outcomes of taTME and the related progress of postoperative function. The results showed that there were no significant differences in the main short-term and long-term efficacy between taTME and traditional laparoscopic TME, but taTME had potential advantages in postoperative functional recovery. The results of case study after passing the learning curve suggested that taTME had better short-term and long-term efficacy. Moreover, with the maturity of taTME technology, transanal endoscopic surgery has gradually shown its advantages in the treatment of complex pelvic diseases. In the future, the application of single-port robot will further promote the development of natural orifice transluminal endoscopic colorectal surgery.

Mouse strain-specific responses of mitochondrial respiratory function and cardiac hypertrophy to isoproterenol treatment / 生理学报

Cardiac hypertrophy is a common pathological process of various cardiovascular diseases and eventually develops into heart failure. This paper was aimed to study the different pathological characteristics exhibited by different mouse strains after hypertrophy stimulation. Two mouse strains, A/J and FVB/nJ, were treated with isoproterenol (ISO) by osmotic pump to induce cardiac hypertrophy. Echocardiography was performed to monitor heart morphology and function. Mitochondria were isolated from hearts in each group, and oxidative phosphorylation function was assayed in vitro. The results showed that both strains showed a compensatory enhancement of heart contractile function after 1-week ISO treatment. The A/J mice, but not the FVB/nJ mice, developed significant cardiac hypertrophy after 3-week ISO treatment as evidenced by increases in left ventricular posterior wall thickness, heart weight/body weight ratio, cross sectional area of cardiomyocytes and cardiac hypertrophic markers. Interestingly, the heart from A/J mice contained higher mitochondrial DNA copy number compared with that from FVB/nJ mice. Functionally, the mitochondria from A/J mice displayed faster O

Effects of Buyang Huanwu Decoction on Hemorheology and Platelet Related Biological Indexes in Hyperlipidemia Model Rats / 中国药房

OBJECTIVE：To investigate the effe cts of Buyang huanwu decoction on hemorheology and platelet related biological indexes of hyperlipidemia model rats. METHODS ：Male Wistar rats were randomly divided into blank control group （10 rats）and model group （40 rats）. Blank control group was given normal diet ，and model group was given high-lipid diet for 6 weeks at least to induce hypelipidemia model. After modeling ，rats were randomly divided into model control group ，positive control group （simvastatin，0.004 g/kg），Buyang huanwu decoction low-dose and medium-dose groups （3.5，14.0 g/kg，by crude drug），with 10 rats in each group. Blank control group and model control group were given normal saline intragastrically ， administration groups were given relevant drug intragastrically ，0.01 mL/g，once a day ，for consecutive 4 weeks. Thirty min after last medication ，hemorheological indexes （whole blood viscosity ，plasma viscosity ），platelet adhesion related indexes [adhesion rate，von Willebrand factor （vWF），fibronectin（FN）]，platelet release related indexes [ β-thromboglobulin（β-TG），platelet factor 4 （PF4）] and platelet fibrinolytic system related indexes [tissue plasminogen activator （t-PA），plasminogen activator inhibitor （PAI-1）]，platelet parameters （PLT，PDW，MPV，PCT，PLCR），4 kinds of coagulation parameters （APTT，TT，PT，FIB）were detected. RESULTS ：Compared with blank control group ，the whole blood viscosity （low，medium and high shear rate ），plasma viscosity，platelet adhesion rate ，the contents or levels of vWF ，FN，β-TG，PAI-1，PLT，MPV，PCT，PLCR and FIB in model control group were increased significantly （P＜0.05 or P＜0.01），and t-PA content was significantly decreased （P＜0.05）. Compared with model control group ，the whole blood viscosity （except for whole blood viscosity of high shear rate in Buyang huanwu decoction high-dose group ），plasma viscosity ，platelet adhesion rate ，the contents or levels of vWF ，FN，β-TG，PAI-1， PLT，PDW（except for Buyang huanwu decoction low-dose and high-dose groups ），MPV，PCT，PLCR（except for Byang huanwu decoction low-dose group ）and FIB were decreased significantly （P＜0.05 or P＜0.01），while t-PA content （except for positive control group ） was increased significantly （P＜0.05）. CONCLUSIONS ：Buyang huanwu decoction can significantly improve the pathological state in hyperlipidemia model rats by reducing blood viscosity and FN content ，improving platelet adhesion，enhancing fibrinolytic activity ，improving platelet aggregation ，inhibiting hypercoagulability and hyperplatelet release.

Clinical Significance of C-X-C Motif Chemokine Receptor 4 and Integrin αvβ6 Expression in Breast Cancer / 한국유방암학회지

Purpose@#C-X-C motif chemokine receptor 4 (CXCR4) and integrin αvβ6 play important roles in the malignant progression of multiple cancers. However, it remains unclear whether the expression of one or both proteins in breast cancer (BC) is of clinical significance. In this study, we investigated the expression of CXCR4 and integrin αvβ6 in BC tissues and their correlation with clinicopathological characteristics, including survival. @*Methods@#CXCR4 and αvβ6 expression in 111 BC tissues was examined by immunocytochemistry. Correlations between the expression of the 2 proteins and patient clinicopathological characteristic were investigated using the Kaplan–Meier method and the Cox proportional hazards model. @*Results@#CXCR4 and αvβ6 were overexpressed in BC tissue compared with normal breast tissue. Overexpression of both molecules was related to lymph node status (p = 0.013 and p = 0.022, respectively). αvβ6 overexpression was also associated with tumor size (p = 0.044). A positive correlation was detected between the expression of CXCR4 and αvβ6 (r = 0.649, p = 0.001), and co-overexpression of both molecules was associated with tumor size (p = 0.018) and lymph node metastasis (p = 0.015). Kaplan–Meier analysis revealed that overexpression of CXCR4, αvβ6, or both molecules was associated with short overall survival (OS; p < 0.001, p < 0.001, and p = 0.009, respectively) and disease-free survival (DFS; p < 0.001, p = 0.005, and p = 0.019, respectively). Multivariate analysis indicated that lymph node metastasis was an independent prognostic factor for unfavorable OS and DFS (p = 0.002 and p = 0.005, respectively), whereas co-overexpression of CXCR4 and αvβ6 was an independent prognostic factor only for OS (p = 0.043). @*Conclusion@#CXCR4 and αvβ6 may play synergistic roles in the progression of BC, and co-targeting of CXCR4 and αvβ6 could be a potential strategy for the prevention and treatment of BC.

Advance on the pharmacological research of dioscin / 中国药理学通报

Dioscin is the main ingredient of Dioscorea,a tradi-tional medical herb.Traditional theory of Chinese medicine be-lieves that Dioscorea has effects of clearing lung,digesting food, diuresis, improving blood circulation, relaxing muscles and stopping attack of malaria.Pharmacological studies have shown that dioscin has many pharmacological effects,particularly the anti-tumor effect.Many studies have also shown dioscin im-proves symptoms of atherosclerosis and protects blood vessel en-dothelium,reduces ischemia-reperfusion injury of heart,brain and kidney,lowers blood sugar,inhibits hepatic fibrosis,im-proves menopausal osteoporosis,relieves rheumatoid arthritis, ulcerative colitis and other inflammatory disorders,and posses-ses anti-bacterial and anti-viral activity.This article focuses on the progress of the modern pharmacological study of dioscin,and reports its advances in recent years.

Role of noncoding RNA in vascular injury, remodeling and aging / 中国药理学通报

Non-coding RNAs ( ncRNA ), including ribosomal RNA( rRNA), transfer RNA( tRNA), MicroRNA ( miRNA), long noncoding RNA(lncRNA) and small nucleolar RNA(snoR-NA), are a class of RNA that have multiple functions and are not translated to proteins. MicroRNA and lncRNA are involved in the injury, remodeling and aging of blood vessels, and it is necessary to understand the regulatory roles of MicroRNA and lncRNA in these processes. It is reported that MicroRNA and lncRNA are not only participated in the regulation of oxidative response, inflammation, cell proliferation and migration, and phenotype transition, they are also involved in the regulation of gene expression by conducting different mechanisms, including transcriptional regulation, post-transcriptional modification and chromatin remodeling. These aspects of regulation by MicroRNA and lncRNA are related to cardiovascular diseases, such as ath-erosclerosis, hypertension, myocardial infarction, stroke, pul-monary hypertension and diabetes, and thus provide a new way for genetic diagnosis and therapy of cardiovascular diseases.

The research progress of senescence-associated secretory phenotype / 中国药理学通报

When senescence induction is based on DNA damage, senescent cells display a unique phenotype, which has been termed “senescence-associated secretory phenotype”( SASP ) . SASP, including proinflammatory cytokines, growth factors, chemokines, matrix remodeling enzymes and other cytokines, may be an important driver of chronic inflammation and therefore may be part of a vicious cycle of inflammation, DNA damage and senescence. Senescence-associated secretory products released by such cells can affect the neighboring cells and further exacer-bate their regenerative capacity. SASP is associated with many chronic age-related diseases.