OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

This study mainly explores the role of myeloid differentiation primary response protein 88 (MyD88) in tumorigenesis and development, to identify active compounds targeting MyD88. CRISPR/Cas9 system and xenograft tumor model were used to detect the effect of MyD88 deletion on tumor growth, and the experimental animal ethics review number was PZSHUTCM200828006. Microscale thermophoresis technology (MST) was used to identify compounds directly bind to MyD88 and further detect the impact of candidate small molecules on cell proliferation. Results showed that depletion of MyD88 significantly inhibited xenograft tumor growth of colon cancer, pancreatic cancer and skin cancer and the activity of NF-κB signaling pathway. MST showed that nordihydroguaiaretic acid (NDGA) bound to MyD88, with the binding dissociation constant K_d of 14.61 µmol·L^-1. NDGA inhibited NF-κB reporting system activation and phosphorylation of p65, the key factor in NF-κB signal pathway. In addition, the results of colony formation assay showed that NDGA suppressed the proliferation of tumor cells. The above results show that, MyD88 is a potential therapeutic target for colon cancer, pancreatic cancer and skin cancer, NDGA directly binds to MyD88 and inhibits the activity of NF-κB signaling pathway, as well as inhibits the proliferation of pancreatic cancer, skin cancer and colon cancer cells.

Huachansu is a traditional Chinese medicine widely used in the clinic for cancer therapy, while the underlying mechanism is not fully clarified. This study was to investigate the targets and mechanisms of cinobufagin (CBG), an active component of Huachansu, in terms of blocking mitosis of cancer cells. Propidium iodide (PI) DNA staining was used to analyze the effect of CBG on cell cycle. The effect of CBG on mitosis of cancer cells was examined by α-tubulin and pericentrin staining after synchronization by a double thymidine block. Tubulin turbidity, tubulin polymerization and α‍-tubulin immunofluorescence assays were used to evaluate the effect of CBG on microtubule polymerization. CRISPR/Cas9 gene-editing technology was used to knockout microtubule-severing protein Katanin regulatory subunit B1 (KATNB1) in HCT116 cells, and the inhibitory effect of CBG on wild-type cells and knockout cells was measured by CCK-8. The engagement of CBG with KATNB1 was measured by CETSA and DARTS assays. The effect of CBG on KATNB1 protein and mRNA level was examined by Western blot and real-time PCR, respectively. Our data showed that CBG arrested HCT116 cell cycle at the G₂/M phase, disrupted mitosis and induced centriole overduplication. CBG significantly inhibited tubulin polymerization in vitro and in vivo. The cytotoxicity of CBG inhibition on HCT116 was significantly attenuated upon KATNB1 depletion. Moreover, CBG bound to KATNB1 and decreased its protein level, while mutated KATNB1 weakened this effect. In conclusion, CBG inhibited microtubule polymerization via targeting KATNB1, thereby disrupting mitosis in cancer cells.

The prevention and treatment of scars has always been an important task in the field of wound repair.Humans have started treatment for scars long time ago and have created a series of treatments.At the same time,with the development of science and technology,the diagnosis and treatment of scars have made great progress.Through the basic research for new therapeutic targets and innovative of treatment methods,treatment for scar turns more diversified and integrated.As a result,clinicians will suffer many challenges while having more options for scars treatment.Combined with traditional treatment,developing new treatments,and the comprehensive therapy of multiple treatment methods is the mainstream trend of scar treatment.

Adult ; Humans ; Language ; MELAS Syndrome ; diagnostic imaging ; physiopathology ; Male ; White Matter ; diagnostic imaging ; physiopathology

Objective·To explore the value of applying CT/MRI image registration and fusion combined with 3D printing technique in pre-surgical planning of refractory pelvic tumors. Methods·A retrospective analysis was performed on the cases with refractory pelvic tumors admitted between March 2014 and December 2016 in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. CT/MRI examinations were performed as a routine pre-surgical procedure, and the resulting images were subject to rapid registration and fusion with the Medraw software in order to accurately determine the tumor boundaries and to be used as references in designing and making patient-specific tumor models, prostheses, and implants by 3D printing technique. Results·A total of 13 cases with refractory pelvic tumors were included in this study (8 cases of chondrosarcoma, 1 case of osteosarcoma with aneurysmal bone cyst, 1 case of dedifferentiated sarcoma, 1 case of fibrous connective tissue hyperplasia, 1 case of solitary fibrous tumor/hemangiopericytoma, and 1 case of metastatic squamous cell carcinoma) with an average age of (50.0±8.5) years. According to the Enneking classification,there were 2 cases in zone Ⅰ , 2 in zones Ⅰ + Ⅱ , 1 in zones Ⅱ + Ⅲ , 3 in zones Ⅰ + Ⅱ + Ⅲ , 1 in zones Ⅰ + Ⅱ + Ⅳ , 1 in zonesⅠ + Ⅱ + Ⅲ + Ⅳ , 1 in zones Ⅰ + Ⅳ , 1 in zones Ⅱ + Ⅳ , and 1 in zone Ⅳ. The mean maximal tumor diameter was (15.15±4.81) cm without implicating the pelvic blood vessels. Results from intraoperative frozen section at resection boundaries and the installation of prosthesis showed that the actual surgical procedure was consistent with the surgical planning based on the reported image fusion technique. Conclusion·CT/MRI image registration and fusion technique combined with 3D printing technique can accurately determine the resection boundary of pelvic tumors and assist in designing of individualized prosthesis model and surgical guide, which has a great value in pre-surgical planning and clinical treatment of refractory pelvic tumors.

OBJECTIVETo evaluate the early clinical effects of arthroscopic treatment for cruciate ligament cysts of the knee.

METHODSFrom September 2008 to January 2014, 23 patients with cruciate cysts were treated with arthroscopic surgery. There were 11 males and 17 females, with an average age of 28.3 years old (ranged, 16 to 56 years old). Twenty patients had injuries on the right knee and 8 patients had injuries on the left knee. Eight patients had a history of injury,5 patients had a history of chronic injury,and the other 15 patients had no obvious reasons for the symptom. Before the operation, 24 patients were clearly diagnosed as the cruciate ligament cysts of knee joint,and 4 patients were diagnosed as other problems of the knee, but the diagnosis were corrected after the operation. According to the MRI before the surgery,all the patients could be divided into 3 types: 14 were type I, 6 were type II, 8 were type III. After the operation, the patients were suggested to have a rest for 2 weeks, and take exercises everyday at the same time. The knee range of motion, Lysholm score, International Knee Documentation Committee (IKDC) 2000 subjective score, GLASGOW criteria, and McMurray test, pivot shift test, and anterior drawer test were observed to evaluate clinical results.

RESULTSAll the incisions healed at the first stage without complications. Twenty-five patients were followed up, and the duration ranged from 12 to 52 months, with a mean of 26.7 months. Three patients accepted the reconstruction of ACL or tightened elongated ACL using bipolar radio frequency. The Lysholm score increased from preoperative 59.80 +/- 6.58 to 75.32 +/- 6.49 at the latest follow-up; IKDC 2000 score increased from preoperative 65.36 +/- 6.26 to 81.00 +/- 5.76 at the latest follow-up. According to GLASGOW criteria,23 patients got an excellent result and 2 good.

CONCLUSIONIt has a satisfactory curative effect on ACL reconstruction using bipolar radio frequency. It has advantages of firm fixation, simple and secure operation as well as quick postoperative recovery. It's very important to check the MRI before operations, and carefully seek the cysts during the operations, avoiding the omission of any cysts,especially the cases of multiple cysts. Finally, patients should take exercises actively after operations.

Adolescent ; Adult ; Anterior Cruciate Ligament ; physiopathology ; surgery ; Anterior Cruciate Ligament Injuries ; Anterior Cruciate Ligament Reconstruction ; Arthroscopy ; Cysts ; surgery ; Female ; Humans ; Knee Injuries ; physiopathology ; surgery ; Knee Joint ; physiopathology ; surgery ; Male ; Middle Aged ; Range of Motion, Articular ; Young Adult

OBJECTIVETo explore type 2 diabetes prevalence and its risk factors among migrants and nonmigrants aged 35 years and older in Three Gorge Dam area in Yichang City of Hubei province, China.

METHODSA sample of 9865 rural residents (including 1949 Three Gorge Dam migrants and 7916 nonmigrants) aged 35 years old and over was selected from September to December in 2007 by the method of multi-stage cluster random sampling in Yiling district, Yichang City of Hubei province. The study subjects were assessed by interview, examination, and blood samples. Information on demographics, migrant information, lifestyle, history of diabetes and hypertension was obtained by a questionnaire interview. An overnight fasting blood specimen was collected to measure serum glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C). Height, weight, waist circumference, hip circumference and blood pressure were measured. Oral glucose tolerance test (OGTT) was carried out for those whose fasting glucose was equal to or exceeded 6.1 mmol/L. The standardized prevalence of type 2 diabetes was calculated based on national census in the year of 2000. Multiple logistic regression analysis was used to explore the potential risk factors of type 2 diabetes.

RESULTSThe crude prevalence of type 2 diabetes among nonmigrants was 3.93% (310/7885) (male: 3.90% (129/3304), female: 3.95% (181/4581)), and that of migrants was 6.55% (127/1939) (male: 6.85% (52/759), female: 6.36% (75/1180)). The crude prevalence of type 2 diabetes among migrants was higher than that of nonmigrants (χ² = 25.10, P < 0.01 (male: χ² = 12.59, P < 0.01; female: χ² = 12.78, P < 0.01)). The prevalence of type 2 diabetes among nonmigrants was 3.87% in males and 4.15% in females. The standardized prevalence of type 2 diabetes among migrants was 6.92% in males and 6.33% in females. Logistic regression analysis showed that age (taking 35 - 44 years old as reference, 45 - 54 years old: OR = 1.45, 95%CI: 1.07 - 1.95; 55 - 64 years old: OR = 2.08, 95%CI: 1.53 - 2.84; 65 years old and over: OR = 1.85, 95%CI: 1.25 - 2.75), family history of diabetes (OR = 2.83, 95%CI: 1.70 - 4.72), overweight or obesity (overweight: OR = 1.36, 95%CI: 1.05 - 1.78; obesity: OR = 2.11, 95%CI: 1.47 - 3.01), central obesity (OR = 1.84, 95%CI: 1.39 - 2.44), abnormal triglyceride (OR = 1.54, 95%CI: 1.21 - 1.97), abnormal total cholesterol (OR = 1.40, 95%CI: 1.11 - 1.77) and abnormal LDL-C (OR = 1.82, 95%CI: 1.19 - 2.79) increased the risk of type 2 diabetes, and regular physical activity (OR = 0.57, 95%CI: 0.45 - 0.72) was the protective factor of type 2 diabetes.

CONCLUSIONThe prevalence of type 2 diabetes among Three Gorge Dam migrants was higher than that of nonmigrants. Increasing age, regular physical activity, family history of diabetes, overweight or obesity, central obesity, abnormal triglyceride, abnormal total cholesterol and abnormal LDL-C were related to type 2 diabetes.

Adult ; Aged ; China ; epidemiology ; Diabetes Mellitus, Type 2 ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Transients and Migrants

Objective To evaluate the epidemiological features and control status of hypertension in rural area of The Three Gorges. Methods A cross-sectional survey was carried out in mral area of Yiling District, Yichang City, which was located north-west bank of Xiling Gorges in 2007. A standard structure questionnaire was used to collect data on the hypertension history and treatment, social-economic status and life-styles, and so on. Blood pressure was measured by trained observers using standardized mercury sphygmomanometer. Hypertension was defined as systolic blood pressure ≥ 140 mm Hg( 1 mm Hg =0. 133kPa) and/or diastolic ≥90 mm Hg, or current treatment with antihypertensive medications. Hypertension control was defined as blood pressure levels of less than 140/90 mm Hg. Results A total of 9618 residents aged 35 years and above were included ( response rate: 81.3％ ), and 19. 7％ residents were the Three Gorges migrants. The age-adjusted prevalence of hypertension was 37.3％ for all, and 21.3％, 39. 8％,58.0％ for aged 35-44, 45-59, ≥60 years, respectively. The age-adjusted rate was higher in men for all (39.1％) and aged 35-44 years (27.0％) than in women (36.3％ for all and 17.8％ for aged 35-44years, P ＜ 0. 01 ). The age-adjusted rate of awareness, treatment and control rates of hypertension were lower in men (18.5％, 9. 0％, 0.9％, respectively) than in women (23.5％, 13.6％, 2. 0％,respectively, all P ＜ 0.01 ).Among the participants with treated hypertension, the control rate of hypertension was only 17.0％. Prevalence and rate of awareness, treatment and control of hypertension were similar between migrants and non-migrants. Conclusion The prevalence of hypertension is high, but the awareness, treatment, control rates were low in rural area of Yiling District. Efforts should be made to reduce the prevalence rate and to improve the control rate of hypertension in this area.

Objective Through the unified and standardized management of the rescue vehicle,to ensure rescue items complete integrity, fast and effective.Methods Standard configuration in emergency medicine,placement,storage,registration of all aspects evaluate were unified Results The time for rescuing and counting stuffs,satisfied degree of doctors and valid time of medicine were significantly improved after quality control(P<0.01).Conclusions Standard management of the rescue vehicles could ensure medicines fast.safe and effective.It is worthy of clinical application widely.