Doublecortin-like kinase 1 activates Hippo pathway to promote migration, invasion and proliferation of pancreatic cancer cells / 中华肿瘤杂志

Objective: To explore the mechanism of Doublecortin-like kinase 1 (DCLK1) in promoting cell migration, invasion and proliferation in pancreatic cancer. Methods: The correlation between DCLK1 and Hippo pathway was analyzed using TCGA and GTEx databases and confirmed by fluorescence staining of pancreatic cancer tissue microarrays. At the cellular level, immunofluorescence staining of cell crawls and western blot assays were performed to clarify whether DCLK1 regulates yes associated protein1 (YAP1), a downstream effector of the Hippo pathway. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to analyze the expressions of YAP1 binding transcription factor TEA-DNA binding proteins (TEAD) and downstream malignant behavior-promoting molecules CYR61, EDN1, AREG, and CTGF. Transwell test of the DCLK1-overexpressing cells treated with the Hippo pathway inhibitor Verteporfin was used to examine whether the malignant behavior-promoting ability was blocked. Analysis of changes in the proliferation index of experimental cells used real-time label-free cells. Results: TCGA combined with GTEx data analysis showed that the expressions of DCLK1 and YAP1 molecules in pancreatic cancer tissues were significantly higher than those in adjacent tissues (P<0.05). Moreover, DCLK1was positively correlated with the expressions of many effectors in the Hippo pathway, including LATS1 (r=0.53, P<0.001), LATS2 (r=0.34, P<0.001), MOB1B (r=0.40, P<0.001). In addition, the tissue microarray of pancreatic cancer patients was stained with multicolor fluorescence, indicated that the high expression of DCLK1 in pancreatic cancer patients was accompanied by the up-regulated expression of YAP1. The expression of DCLK1 in pancreatic cancer cell lines was analyzed by the CCLE database. The results showed that the expression of DCLK1 in AsPC-1 and PANC-1 cells was low. Thus, we overexpressed DCLK1 in AsPC-1 and PANC-1 cell lines and found that DCLK1 overexpression in pancreatic cancer cell lines promoted YAP1 expression and accessible to the nucleus. In addition, DCLK1 up-regulated the expression of YAP1 binding transcription factor TEAD and increased the mRNA expression levels of downstream malignant behavior-promoting molecules. Finally, Verteporfin, an inhibitor of the Hippo pathway, could antagonize the cell's malignant behavior-promoting ability mediated by high expression of DCLK1. We found that the number of migrated cells with DCLK1 overexpressing AsPC-1 group was 68.33±7.09, which was significantly higher than 22.00±4.58 of DCLK1 overexpressing cells treated with Verteporfin (P<0.05). Similarly, the migration number of PANC-1 cells overexpressing DCLK1 was 65.66±8.73, which was significantly higher than 37.00±6.00 of the control group and 32.33±9.61 of Hippo pathway inhibitor-treated group (P<0.05). Meanwhile, the number of invasive cells in the DCLK1-overexpressed group was significantly higher than that in the DCLK1 wild-type group cells, while the Verteporfin-treated DCLK1-overexpressed cells showed a significant decrease. In addition, we monitored the cell proliferation index using the real-time cellular analysis (RTCA) assay, and the proliferation index of DCLK1-overexpressed AsPC-1 cells was 0.66±0.04, which was significantly higher than 0.38±0.01 of DCLK1 wild-type AsPC-1 cells (P<0.05) as well as 0.05±0.03 of DCLK1-overexpressed AsPC1 cells treated with Verteporfin (P<0.05). PANC-1 cells showed the same pattern, with a proliferation index of 0.77±0.04 for DCLK1-overexpressed PANC-1 cells, significantly higher than DCLK1-overexpressed PANC1 cells after Verteporfin treatment (0.14±0.05, P<0.05). Conclusion: The expression of DCLK1 is remarkably associated with the Hippo pathway, it promotes the migration, invasion, and proliferation of pancreatic cancer cells by activating the Hippo pathway.

Curative effects of Shugan Hewei Zhitong Recipe on chronic gastritis complicated by Helicobacter pylori infection / 中国基层医药

Objective:To investigate the curative effects of Shugan Hewei Zhitong Recipe on chronic gastritis complicated by Helicobacter pylori infection. Methods:Eighty-seven patients with chronic gastritis complicated by Helicobacter pylori infection who received treatment in the Huguosi Hospital of Traditional Chinese Medicine, Beijing University of Chinese Medicine, China from July 2018 to June 2020 were included in this study. They were randomly assigned to undergo treatment with either conventional Western medicine ( n = 43, control group) or Shugan Hewei Zhitong Recipe based on conventional Western medicine ( n = 44, observation group) for 2 weeks. Before and after treatment, traditional Chinese medicine syndrome scores were compared between the two groups. Curative effects of Shugan Hewei Zhitong Recipe on chronic gastritis complicated by Helicobacter pylori infection were evaluated. Results:Total response rate in the observation group was significantly higher than that in the control group [91% (40/44) vs. 72% (31/43), χ2 = 5.13, P = 0.024]. In each group, the traditional Chinese medicine symptom score post-treatment was significantly lower than the traditional Chinese medicine symptom score pre-treatment (both P < 0.001). After treatment, the traditional Chinese medicine score of the observation group was significantly lower than that of the control group ( P < 0.05). There were no adverse reactions in each group. Conclusion:Shugan Hewei Zhitong Recipe is safe and effective on chronic gastritis complicated by Helicobacter pylori infection, which is worthy of clinical promotion.

Clinical study of serum human-βeta-defensin-1 level for evaluating short-term prognosis in patients with acute-on-chronic liver failure / 中华肝脏病杂志

Objective: To evaluate the diagnostic value of serum human-βeta-defensin-1 level (HBD-1) for short-term (28-day) prognosis in patients with acute-on-chronic liver failure (ACLF). Methods: Fifty cases diagnosed with ACLF were selected. 20 cases with decompensated cirrhosis and 20 cases with compensated cirrhosis who were admitted at the same time were included. Age, gender, serum HBD-1 level, C-reactive protein (CRP), procalcitonin (PCT), neutrophil count/lymphocyte ratio (NLR), blood routine, coagulation function, liver function, kidney function, and other indicators from the three groups of patients were collected. Patients with ACLF were screened for indicators related to the short-term (28-day) prognosis. Patients were divided into an improvement group and a worsening group according to the 28-day disease outcome. The serum HBD-1 level and other above-mentioned indicators were compared between the two patient groups. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of serum HBD-1 levels for short-term prognosis in patients with ACLF. PCT, NLR, and prothrombin activity (PTA) application as a mono indicator and HBD-1 in combination with NLR, PCT, and PTA were compared to evaluate diagnostic efficacy for short-term prognosis in patients with ACLF. The intergroup mean of measurement data was determined using a t-test or analysis of variance. χ (2) test was used for comparison of count data. Spearman's rank correlation analysis was used for correlation analysis. Results: There was no statistically significant difference in age and gender among the three groups: ACLF, decompensated cirrhosis, and compensated cirrhosis (P > 0.05). The expression levels of serum HBD-1 in the ACLF group, decompensated cirrhosis group, and compensated cirrhosis group were (319.1 ± 44.4) ng/ml, (264.5 ± 46.5) ng/ml and (240.1 ± 35.4) ng/ml, respectively, while the ACLF group expression levels were significantly increased, with statistical significance (P < 0.01).The serum HBD-1 level was significantly higher in the ACLF worsening group (346.2 ± 43.6) ng/ml than that in the improvement group (308.5 ± 40.6) ng/ml, and the difference was statistically significant (P < 0.05). Correlation analysis showed that HBD-1, NLR, PCT, prothrombin time (PT), and international standardized ratio (INR) were negatively correlated with the 28-day disease outcome (improvement) of patients (P < 0.05). PTA was positively correlated with 28-day disease outcome (improvement) (P < 0.05). The area under the receiver operating characteristic curve (AUC) for evaluating HBD-1's diagnostic efficacy for short-term prognosis in patients with ACLF was 0.774, with a sensitivity of 0.750, a specificity of 0.786, and a cut-off point of 337.96 ng/ml. PCT, NLR, and PTA had greater diagnostic efficacy. HBD-1 combined with PTA had the highest diagnostic efficacy, with an AUC of 0.802, a sensitivity of 0.778, and a specificity of 0.786. The diagnostic efficacy of HBD-1+PCT, HBD-1+NLR and HBD-1, PCT, and NCR was superior to PTA mono. Conclusion: The serum HBD-1 level gradually increases with the aggravation of liver function injury and is negatively correlated with the short-term prognosis in patients with ACLF. Serum HBD-1 level has high sensitivity and specificity in predicting short-term prognosis in patients with ACLF, and its diagnostic efficacy is superior to that of PCT, NLR, and PTA. The combined application of HBD-1 and PTA has higher diagnostic efficacy; however, when the serum HBD-1 level is greater than 337.96ng/ml, it indicates poor prognosis in patients.

Comparison of ARIMA models with and without covariates in the prediction of HIV infection among young students in Dalian / 公共卫生与预防医学

Objective To compare the effect of ARIMA models with and without covariates in predicting the number of HIV infections among young students in Dalian. Methods First, univariate correlation analysis was performed on the network, STD sequence and HIV sequence to understand whether there was a correlation and lag relationship between them. Secondly, variables with the strongest correlation and predictive value and HIV infection numbers were used as the baseline data to establish an ARIMA model with covariates and a general ARIMA model without covariates, and to predict the HIV number from 2019 to 2021. The average absolute errors were used as evaluation indexes to compare the prediction effects of the two models. Results A total of 841 cases of HIV infection among young students were reported in Dalian from 2013 to 2021. The results of univariate correlation analysis showed that the search index of the keyword AIDS in the Baidu Index in a given month from 2013 to 2019 was significantly positively correlated with the number of HIV infections in that month (r=0.302, P=0.006), and gonorrhea was negatively correlated with the number of HIV infections with a lag of 2 months (r=-0.250, P =0.024). Using gonorrhea incidence number and HIV infection number as the basic data, an ARIMA model with covariates and a general ARIMA model without covariates were established to predict the number of HIV infection among young students from 2019 to 2021, and the average absolute errors were 17.621% and 66.17%, respectively. Conclusion Compared with the general ARIMA model without covariates, the ARIMA model based on the combined use of STD incidence and HIV infection is more suitable for predicting the number of HIV infections among young students in Dalian, but the average absolute error of the model is still large, which needs further improvement in the future research.

Processing Magnoliae Officinalis Cortex with ginger juice: process optimization based on AHP-CRITIC weighting method and composition changes after processing / 中国中药杂志

The weight coefficients of appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol were determined by analytic hierarchy process(AHP), criteria importance though intercrieria correlation(CRITIC), and AHP-CRITIC weighting method, and the comprehensive scores were calculated. The effects of ginger juice dosage, moistening time, proces-sing temperature, and processing time on the quality of Magnoliae Officinalis Cortex(MOC) were investigated, and Box-Behnken design was employed to optimize the process parameters. To reveal the processing mechanism, MOC, ginger juice-processed Magnoliae Officinalis Cortex(GMOC), and water-processed Magnoliae Officinalis Cortex(WMOC) were compared. The results showed that the weight coefficients of the appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol determined by AHP-CRITIC weighting method were 0.134, 0.287, and 0.579, respectively. The optimal processing parameters of GMOC were ginger juice dosage of 8%, moistening time of 120 min, and processing at 100 ℃ for 7 min. The content of syringoside and magnolflorine in MOC decreased after processing, and the content of honokiol and magnolol followed the trend of GMOC>MOC>WMOC, which suggested that the change in clinical efficacy of MOC after processing was associated with the changes of chemical composition. The optimized processing technology is stable and feasible and provides references for the modern production and processing of MOC.

Standards for the interpretation of constitutional copy number gain: Recommendation from the American College of Medical Genetics and Genomics (ACMG) and Clinical Genome Resource (ClinGen) / 中华医学遗传学杂志

Copy number variants (CNVs) are common causes of human genetic diseases. CNVs detection has become a routine component of genetic testing, especially for pediatric neurodevelopmental disorders, multiple congenital abnormalities, prenatal evaluation of fetuses with structural anomalies detected by ultrasound. Although the technologies for CNVs detection are continuously improving, the interpretation is still challenging, with significant discordance across different laboratories. In 2020, the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) developed a guideline for the interpreting and reporting of constitutional copy number variants, which introduced a quantitative, evidence-based scoring framework. Here, we detailed the key points of interpreting the copy number gain based on the guideline, used six examples of different categories to illuminate the scoring process and principles. We encourage a professional understanding and application of this guideline for the detected copy number gains in China in order to further improve the clinical evaluation accuracy and consistency across different laboratories.

Effects of Zhongfeng capsule on autophagy related proteins expressions of brain tissue in rats with cerebral ischemia/reperfusion injury / 中国应用生理学杂志

Objective: To investigate the effects of Zhongfeng capsule on the autophagy-related proteins expression in rats with cerebral ischemia/reperfusion injury (CI/ RI), and to explore its neural protection mechanisms of the decoction. Methods: Rat middle cerebral artery ischemia/reperfusion injury model (ischemia for 2 h, reperfusion for 24 h) was prepared by the improved line plug method. Sixty male SD rats were randomly divided into sham operation group, model group, butylphthalide group(0.054 g/kg), Zhongfeng capsule high-dose groups (1.08 g/kg), Zhongfeng capsule middle-dose groups (0.54 g/kg), Zhongfeng capsule low-dose groups (0.27 g/kg), with 10 rats in each group. Rats were treated with Zhongfeng capsule by gavage once a day for 10 days. The rats were sacrificed and the brain tissue was obtained after the experiment in each group. Score neurological deficit was evaluated after 24 h of the last intervention in rat of each group. The pathological changes of brain tissue were observed by HE staining. The serum levels of estradiol (E2) and follicle stimulating hormone (FSH) were determined by ELISA. The expressions of key genes and proteins of PI3K/Akt/Beclin1 signaling pathway in brain tissue were detected by qRT-PCR and Western blot respectively. Results: Compared with the sham operation group, the body weight and protein expressions of p-PI3k and p-Akt in brain tissue of rats were decreased significantly in the model group, while the brain index, neurological deficit score, gene and protein expressions of Beclin1 and LC3 were increased markedly in the model group(P＜0.05 or P＜0.01). In the model group, nerve cells of brain tissue were loosely packed, interstitial edema, triangular in shape, nuclear pyknosis and dark-blue staining were observed. Compared with the model group, the body weight of rats was increased obviously, the neurological deficit score was decreased significantly and the pathological injury of brain tissue was alleviated evidently in high-dose of Zhongfeng capsule group (P＜0.05). The brain index, the gene and protein expressions of Beclin1 and LC3 were decreased apparently in Zhongfeng capsule treatment groups(P＜0.05 or P＜0.01), while the expressions of p-PI3k and p-Akt in brain tissue were increased evidently in Zhongfeng capsule treatment groups(P＜0.05 or P＜0.01). Conclusion: Zhongfeng capsule can inhibit autophagy and improve brain neurons lesion of CIRI rats, the mechanism may be related to regulate the expression of Beclin1 and LC3 in PI3K/Akt/Beclin1 signaling pathway.

Research progress of micronucleus visualization analysis and artificial intelligence detection strategy / 中华预防医学杂志

The micronucleomics test can comprehensively display a variety of harmful endpoints, such as DNA damage and repair, chromosome breakage or loss and cell growth inhibition, with fast, simple and economical feature. Micronucleomics is not only widely used in the comprehensive assessment of the types and modes of genetic action of exogenous chemicals (such as drugs, food additives, cosmetics, environmental pollutants, etc.), but also plays an important role in the screening and risk assessment of cancer population at high risk. However, the traditional micronucleomics image counting method has the characteristics of time-consuming, low accuracy, and high cost, which cannot meet the current analysis requirements of large-scale, multi-index, rapidity, high precision and visualization. In recent years, with the rapid development of the era of precision medicine based on big data, visualized analysis of new micronucleomics based on machine learning and detection strategies based on deep learning have shown a good application prospect. This review, based on the application value of micronucleomics, systematically compares the traditional and new artificial intelligence counting of micronucleus images, and discusses the future direction of micronucleus image detection.

Acute Hepatitis Due to Agomelatine Use in Elderly Women with Depression: Case Series

Although agomelatine may be associated with an increased risk of hepatotoxicity, the incidence rate of acute hepatitis seemed divergent between clinical trials and daily practice. Whether aging or gender is a risk factor in developing hepatotoxicity due to agomelatine is not clear. We present 3 older female cases with acute hepatitis occurring due to highly probable idiosyncratic drug-induced liver injury caused by agomelatine. From these cases, regular surveillance on liver function in the older women taking antidepressants would be of benefits.

The clinical study of laparoscopic radical cystectomy for bladder cancer aftar partial cystectomy / 中华泌尿外科杂志

Objective:To discuss the clinical efficacy of laparoscopic radical cystectomy in the treatment of bladder cancer after partial cystectomy.Methods:The clinical data of 30 patients who underwent laparoscopic radical cystectomy after PC in Sichuan Provincial People's Hospital from March 2016 to August 2020 were retrospectively analyzed. Including 24 males and 6 females with an average age was 62.5 (45.5-82.5)years.6 out of 30 cases underwent pelvic lymph node dissection during PC. All patients had definite pathological diagnosis for the high-grade urothelial carcinoma after PC, and the tumor staging was pT 2-3bN 0M 0.5 patients received postoperative adjuvant chemotherapy with gemcitabine and cisplatin, 6 received postoperative adjuvant radiotherapy, 13 received postoperative adjuvant radiotherapy and chemotherapy, and all patients were received maintenance intravesical instillation. Median time for local tumor recurrence after PC was 9(5-29) months, all patients had pathological diagnosis for the high-grade papillary urothelial carcinoma, cT 2-4N 0M 0 stage.The average tumor diameter was 3.5(2.5-4.5)cm, an average number of tumors was 2(1-3). Laparoscopic salvage cystectomy was performed after recurrence.General anesthesia, supine position, 5 ports were inserted through the abdominal approach. Standard pelvic lymph node dissection (PLND) was used to clean the pelvic lymph nodes. Those who had underwent PLND no longer clean the obturator and peripheral iliac vessels, but including the common iliac vessel and the bifurcation of the abdominal aorta and lymphatic tissues around the inferior vena cava, as well as the presacral lymph nodes. Results:All 30surgeries were successfully performed. The average operative time was 270(240-310)min, average estimated intraoperative blood loss was 180(50-300)ml, and there was no blood transfusion during the perioperative period.The average number of lymph nodes dissected was 18 (10-27). There were 4 cases with positive lymph nodes, of which 3 cases were positive for 2 obturator lymph nodes, and 1 case was positive for 3 obturator and external iliac lymph nodes. No serious intraoperative complications occurred.No lymphatic leakage occurred. The average drainage duration was 4(3-7) d, and postoperative hospital stays was 9(7-20)d. The postoperative pathology was invasive high-grade papillary urothelial carcinoma, and pathological TNM stage was pT 2-4aN 0-2M 0.13 patients received postoperative adjuvant chemotherapy. The average postoperative follow-up time was 23(3-31) months. There were 2 cases of pelvic recurrence and 1 case of retroperitoneal lymph node metastasis. These 3 cases received adjuvant chemotherapy and radiotherapy. Conclusions:Radical cystectomy should be the primary treatment for recurrence of bladder cancer after partial cystectomy.

Clinical characteristics and prognosis of young (<35 years) patients with acute ST-segment elevation myocardial infarction / 中华心血管病杂志

Objective: To analyze the risk factors and clinical characteristics as well as long-term prognosis of young patients (aged 18-35 years) with acute ST-segment elevation myocardial infarction (STEMI). Methods: In this retrospective study, from January 2007 to December 2017, STEMI patients who were hospitalized in Beijing Anzhen Hospital, Capital Medical University and younger than 45 years old were collected. Patients were divided to the 18-35 years old group and 36-44 years old group. The basic information of patients, clinical laboratory results, surgical information and discharge diagnosis of enrolled patients were extracted from the electronic medical record system. Subgroup analysis on STEMI patients aged 18 to 35 years was performed to compare the clinical features and outcome of patients with normal coronary angiography or stenotic coronary angiography. Results: 496 patients (20.3%) were between 18 and 35 years old, 480 cases (96.8%) were men, and 371 cases (74.8%) were smokers. The proportion of hypertension and diabetes was lower, but percent of obese (122 cases (43.3%)), level of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), uric acid and homocysteine ​​(Hcy) were significantly higher in patients aged 18 to 35 years compared with STEMI patients aged 36 to 44 years (all P<0.05). In the 18-35 years old group, there were 53 patients (10.7%) with normal coronary angiography and 443 patients (89.3%) with stenosis. The age, proportion of hypertension and diabetes, TC, LDL-C, and triglyceride (TG) levels were lower in the normal coronary angiography group than those in the coronary artery stenosis group (all P<0.05). The main coronary artery lesions were single vessel lesions (263 cases (59.4%)), and the main culprit vessels were left anterior descending artery lesions (238 cases (53.7%)). The follow-up time was 7.0 (4.0, 10.0) years, cardiovascular events were reported in 62 patients (18.9%), of which 14 patients (3.2%) died. The survival rate of patients without cardiovascular events in normal coronary angiography group was higher than that in stenosis group (P=0.029). Multivariate Cox regression analysis showed that diabetes (HR=2.713, 95%CI 1.479-4.976, P=0.001) and dyslipidemia (HR=2.819, 95%CI 1.564-5.079, P=0.001) were independent risk factors for recurrence of cardiovascular events in adult STEMI patients aged 18 to 35 years. Conclusions: STEMI patients aged 18 to 35 years were featured by male sex, obese and smokers. The proportion of hypertension and diabetes was low, while the levels of LDL-C, uric acid and Hcy were high in these patients. Coronary artery stenosis was common, and the stenosis was more likely to occur in the left anterior descending branch. Patients with normal coronary angiography had a better prognosis than those with stenosis. Diabetes and hyperlipidemia increased the risk of recurrent cardiovascular events.

Application of glycan microarrays in cancer research / 生物工程学报

Glycosylation is one of the common post-translational modifications of proteins to regulate the ability of tumor invasion, metastasis and tumor heterogeneity by interacting with glycan-binding proteins such as lectins and antibodies. Glycan microarray can be constructed by chemical synthesis, chemical-enzyme synthesis or natural glycan releasing. Glycan microarray is an essential analytical tool to discover the interaction between glycan and its binding proteins. Here we summarize the standard techniques to construct glycan microarray for the application in cancer vaccine, monoclonal antibody and diagnostic markers.

Effects of Tuina on Muscle-specific microRNA and Factors Related with Proliferation and Differentiation of Muscle Satellite Cells in Denervation-induced Atrophy in Rats / 中国康复理论与实践

Objective:To investigate the effects and mechanism of Tuina on denervation-induced atrophy. Methods:A total of 42 Sprague-Dawley rats were randomly divided into sham group (n = 6), model group (n = 18) and Tuina group (n = 18). The model group and Tuina group freed and excised right tibia nerve about one centimeter, while the sham group freed the right tibia nerve only. From the second day after operation, Tuina group accepted Tuina on the injured area, while the sham group and the model group were only fixed without any intervention. Six rats were sacrificed on the 14th, 21st and 28th day after operation in the model and Tuina groups, and the sham group was sacrificed on the 28th day after operation. The gastrocnemius muscles were measured wet weight ratio. The diameter and area of muscle cells were measured under HE staining. The expression of Pax7, MyoD, MyoG, microRNA-1, microRNA-133a and microRNA-206 in the gastrocnemius muscles were detected with reverse transcription real-time quantitative polymerase chain reaction. Results:Compared with the sham group, the wet weight ratio, the area of muscle cells (except the 14-day-Tuina group) and the diameter of muscle cells decreased at each time point in the model group and Tuina group (P < 0.05); compared with the model group, the wet weight ratio, muscle cell diameter and muscle cell area increased at each time point in Tuina group (P < 0.05). Compared with the sham group, the expression of Pax7 increased in the 14-day-model group (P < 0.05) and decreased in the 28-day-model group (P < 0.05), and it increased at each time point (except 28-day) in Tuina group (P < 0.05); compared with the model group, the expression of Pax7 increased at each time point in Tuina group (P < 0.05). Compared with the sham group, the expression of MyoD and MyoG increased at each time point in the model group and Tuina group (P < 0.05); compared with the model group, the expression of MyoD and MyoG increased at each time point (except 14-day) in Tuina group (P < 0.05). Compared with the sham group, the expression of microRNA-1 and microRNA-133a decreased, and microRNA-206 increased in the model group and Tuina group at 21-day (P < 0.05); compared with the model group, the expression of microRNA-1, microRNA-133a and microRNA-206 increased in Tuina group (P < 0.05). Conclusion:Tuina may activate the Pax7/MyoD/MyoG pathway by increasing the expression of muscle-specific microRNA, to promote the proliferation and differentiation of muscle satellite cells, and delay denervation-induced atrophy.

Clinical trial on the modified Baihe-Gujin Decoction combined with routine chemotherapy for the elderly patients with primary treated pulmonary tuberculosis and lung-kidney yin deficiency / 国际中医中药杂志

Objective:To evaluate the clinical efficacy of modified Baihe-Gujin Decoction combined with routine chemotherapy for the elderly patients with primary treated pulmonary tuberculosis and lung-kidney yin deficiency. Methods:A total of 94 patients who met the inclusion criteria in our hospital from January 2016 to January 2018 were selected and divided into 2 groups according to the random number table method, with 47 patients in each group. The control group was treated with the routine chemotherapy regimen of 2HRZE/4HR (H: isoniazid, R: rifampicin, Z: pyrazinamide, E: ethambutanol), the observation group was treated with Baihe-Gujin Decoction on the basis of the routine chemotherapy. Both groups were treated continuously for 6 months. The sputum negative rate was observed 2, 5 and 6 months after treatment, The closure of cavity shadows was observed by chest CT. The content of IL-6 and IFN-γ-inducible protein-10 were detected by double antibody sandwich ELISA. T cell subsets was detected by flow cytometry. And the clinical efficacy was evaluated. Results:The total effective rate was 87.2% (41/47) in the observation group and 61.7% (29/47) in the control group, and the difference between the two groups was statistically significant ( χ2=8.050, P=0.004). After treatment, the TCM syndrome score of the observation group was significantly lower than that of the control group ( t=5.698, P<0.01). At the end of 6 months after treatment, the sputum negative rate in the observation group was significantly higher than that of the control group ( t=5.317, P=0.021), the effective rate of cavity shadow closure (95.7% with 45/47 vs. 83.0% with 39/47) in the observation group was significantly higher than that of the control group ( χ2=4.029, P=0.044). After treatment, the levels of CD3 +, CD4 + and CD4 +/CD8 + in the observation group were all significantly higher than those in the control group ( t values were 2.107, 3.571 and 2.351, respectively, all Ps<0.05), and the levels of CD8 + in the observation group were all significantly lower than those in the control group ( t=2.711, P=0.005). The levels of IL-6 and IFN-γ-induced protein-10 in the observation group were significantly lower than those in the control group ( t values were 2.517 and 2.890, respectively, all Ps<0.05). Conclusions:The modified Baihe-Gujin Decoction combined with routine chemotherapy can improve the immunity of the elderly patients with primary treated pulmonary tuberculosis with lung-kidney yin deficiency, and improve the clinical efficacy.

Regulatory Mechanism of Youguiwan on Articular Cartilage Degeneration via IL-6/STAT3 Signaling Pathway in Rats with Knee Osteoarthritis / 中国实验方剂学杂志

<b>Objective::To observe the effect of Youguiwan on the levels of cartilage transducers and activators of transcription 3 (STAT3) and interleukin-6 (IL-6) in rats with knee osteoarthritis (KOA). <b>Method::Sixty SD rats were randomly divided into six groups: sham control group, model group, glucosamine sulfate group and Youguiwan (high, middle and low-dose) groups. The modified Hulth method was used to prepare KOA models for 6 weeks. The shame control group and the model group were treated with normal saline, Youguiwan high, middle, low-dose groups received Youguiwan 4.8, 2.4, 1.2 g·kg^-1 by gavage respectively, and the glucosamine sulfate group was treated with glucosamine sulfate 0.17 g·kg^-1. The rats were administrated for 8 weeks according to the dose. After intervention, each group was put to death by femoral artery blood collection, and the keen cartilages of the rats were collected. The pathological changes were observed by htoxylin eosin (HE) staining method, and Mankin score was evaluated. The expressions of STAT3, superoxide dismutase3(SOD3) and Wnt inhibitory factor 1(WIF1) in articular cartilage were detected by immunohistochemistry. The expressions of IL-6 mRNA in articular cartilage were detected by quantitative real-time fluorescence polymerase chain reaction (Real-time PCR). The expression of WIF1 in articular cartilage was detected by Western blot. <b>Result::Compared with the sham control group, the Makin score was obviously increased in the model group, the protein expression of STAT3 was increased significantly, the mRNA of IL-6 was raised significantly, but the protein expression of WIF1 was decreased significantly (<italic>P</italic><0.01), articular cartilage was seriously damaged, and chondrocytes were arranged in disorder. Compared with the model group, the Makin score was declined obviously in the high-dose Youguiwan group, the protein expression of STAT3 was significantly reduced, the mRNA expression of IL-6 was significantly reduced in Youguiwan treatment group, while the protein expression of WIF1 was significantly increased (<italic>P</italic><0.05, <italic>P</italic><0.01), the cartilage structure returned to be normal, the chondrocytes distribution was uneven, and articular cartilage surface was not smooth. <b>Conclusion::Youguiwan could significantly improve the articular cartilage degeneration of KOA rats, and inhibit the inflammation of chondrocytes, which may be related to the suppression of STAT3 and IL-6 expression.

Effect of Tuina on Autophagy-related Factor Beclin-1, Vacuolar Protein Sorting and Microtubule-associated Protein Light Chain 3 in Rats with Denervated Skeletal Muscle Atrophy / 中国康复理论与实践

Objective:To explore the effect and mechanism of Tuina on denervated skeletal muscle atrophy. Methods:A total of 77 male Sprague-Dawley rats were randomly divided into sham group (n = 7), model group (n = 35) and Tuina group (n = 35). The latter two groups were established skeletal muscle atrophy model by exposing and cutting off the common tibial nerve of rats. One day after modeling, the lower limbs of the surgical side received Tuina in Tuina group. Separately, the surgical side of gastrocnemius muscle were sampled on the 0th, 7th, 14th, 21st and 28thday after modeling, and measured the wet mass ratio. The cross-sectional area and diameter of muscle fiber were measured after HE staining. The mRNA expression of autophagy-realated factor Beclin-1, vacuolar protein sorting (Vps34) and microtubule-associated protein light chain 3 (LC3) were tested with reverse transcription real-time quantitative polymerase chain reaction. Results:There was no statistical difference in the ratio of gastrocnemius wet weight, the cross-sectional area and diameter of muscle fiber, and the mRNA expression of Beclin-1, Vps34 and LC3 among three groups on the 0th day (F < 1.321, P > 0.05). Compared with the sham group, the ratio of gastrocnemius wet weight, the cross-sectional area and diameter of muscle fiber decreased at different time points in the model group and Tuina group (P < 0.05), the ratio of gastrocnemius wet weight was higher, and the cross-sectional area and diameter of muscle fiber were bigger, both except on the 21st day, in Tuina group than in the model group (P < 0.05). Compared with the sham group, the mRNA expression of Beclin-1, Vps34 and LC3 increased at different points in the model group than in Tuina group (P < 0.05), and all the mRNA expression was higher, except on the 14th day, in Tuina group than in the model group (P < 0.05). The ratio of gastrocnemius wet weight, the cross-sectional area and diameter of muscle fiber showed a trend of progressive decrease with time in the model group and Tuina group (P < 0.05). The mRNA expression of Beclin-1 and Vps34 increased (P < 0.05), and the mRNA expression of LC3 increased in the model group 21 days after intervention (P < 0.05). The mRNA expression of Beclin-1, Vps34 and LC3 increased first and then decreased, except the mRNA expression on the 14th day in Tuina group (P < 0.05). Conclusion:Tuina may promote the activation of autophagy by up-regulating the expression of autophagy-realated factor Beclin-1, Vps34 and LC3, remove the damaged organelles and proteins, provide certain synthetic substrate and energy for muscle fiber regeneration, thereby reduce the loss of degree of denervated skeletal muscle atrophy.

Effect of Electroacupuncture on Blood-brain Barrier in SAMP8 Mice / 中国康复理论与实践

Objective:To investigate the effects of electroacupuncture on blood-brain barrier to promote intake of drugs into brain of SAMP8 mice. Methods:The male SAMP8 mice (30-week-old) were randomly divided into model group (n = 7), drug group (n = 7), acupuncture group (n = 7) and combined group (n = 7). Other SAMR1 mice were as control group (n = 7). The acupuncture group and the combined group accepted electroacupuncture at Baihui (DU20) and Yintang (EX-HN3), the drug group and the combined group accepted Donepezil, for four weeks. They were observed hippocampus tight junction (TJ) under transmission electron microscope. The activities of acetylcholinesterase (AChE) in hippocampus were detected with immunohistochemistry. The mRNA expression of ZO-1, Claudin-5 and Occludin was detected with real-time quantitative polymerase chain reaction. Results:TJ and basement membrane in the control group, the acupuncture group and the combined group were better than those in the model group and the drug group. AChE was the most in the combined group, and then the drug group and the control group, the acupuncture group and the model group (P < 0.001). The expression of mRNA of ZO-1, Claudin-5 and Occludin was more in the acupuncture group and the combined group than in the drug group (P < 0.01). Conclusion:Electroacupuncture could ameliorate blood-brain barrier disruption and promote drug to enter the brain in SAMP8 mice, which may relate to the adjustion of ZO-1, Claudin-5 and Occludin.

The epigallocatechin gallate derivative Y reverses drug resistance mediated by the ABCB1 transporter both and

Previously, we reported that Y, a new epigallocatechin gallate derivative, is efficacious in reversing doxorubicin (DOX)--mediated resistance in hepatocellular carcinoma BEL-7404/DOX cells. In this study, we evaluated the efficacy of Y in reversing drug resistance both and by determining its effect on the adenosine triphosphate-binding cassette protein B1 transporter (ABCB1 or P-glycoprotein, P-gp). Our results showed that Y significantly sensitized cells overexpressing the ABCB1 transporter to anticancer drugs that are ABCB1 substrates. Y significantly stimulated the adenosine triphosphatase activity of ABCB1. Furthermore, Y exhibited a higher docking score as compared with epigallocatechin gallate inside the transmembrane domain of ABCB1. In addition, in the nude mouse tumor xenograft model, Y (110 mg/kg, intragastric administration), in combination with doxorubicin (2 mg/kg, intraperitoneal injection), significantly inhibited the growth of BEL-7404/DOX cell xenograft tumors, compared to equivalent epigallocatechin gallate. In conclusion, Y significantly reversed ABCB1-mediated multidrug resistance and its mechanisms of action may result from its competitive inhibition of the ABCB1 drug efflux function.

Advance in Mechanism of microRNA Regulating Muscle Atrophy (review) / 中国康复理论与实践

Muscle loses normal function after skeletal muscle atrophy that will greatly reduce the quality of personal life. There is no effective way to treat muscle atrophy currently. microRNA (miRNA) as a small molecule of non-coding RNA brings new hope for the treatment of muscular atrophy. The mechanism of miRNA regulating muscle atrophy mainly includes: regulating abnormal muscle protein metabolism by ubiquitin-proteasome system (UPS) and mammalian target of rapamycin pathway (IGF/PI3K/Akt/mTOR), inhibiting abnormal apoptosis of muscle cells by inhibiting the expression of apoptotic factors, promoting muscle regeneration by regulating myogenic factor expression, and promoting angiogenesis by promoting the expression of angiogenic factors, and so on.

Therapeutic effect of massage on denervated skeletal muscle atrophy in rats and its mechanism / 中国应用生理学杂志

OBJECTIVE@#To investigate the therapeutic effects of massage on denervated skeletal muscle atrophy in rats and its mechanism.@*METHODS@#Forty-eight male SD rats were randomly divided into model group (n=24) and massage group (n=24). Gastrocnemius muscle atrophy model was established by transecting the right tibial nerve of rat. On the second day after operation, the gastrocnemius muscle of the rats in the massage group was given manual intervention and the model group was not intervened. Six rats were sacrificed at the four time points of 0 d, 7 d, 14 d and 21 d. The gastrocnemius of the rats were obtained and measured the wet mass ratio after weighing. Cross-sectional area and diameter of the muscle fiber were measured after HE staining. The relative expressions of miR-23a, Akt, MuRF1 and MAFbx mRNA were tested with qPCR.@*RESULTS@#Compared with 0 d, the wet weight ratio, cross-sectional area and diameter of gastrocnemius muscle showed a progressive decline in the model group and massage group. The wet weight ratio, cross-sectional area and diameter of gastrocnemius muscle in the massage group were higher than those in the model group on 7 d, 14 d and 21 d (P＜0.05, P＜0.01). Compared with 0 d, the expressions of MuRF1, MAFbx and Akt mRNA were increased first and then were decreased in the model group and massage group. The expression of MuRF1 mRNA in massage group was lower than that in model group on 7 d and 21 d (P＜0.05, P＜0.01). The expression of MAFbx mRNA in massage group was lower than that in model group on 7 d, 14 d and 21 d (P＜0.01, P＜0.05, P＜0.01). The expression of Akt mRNA in massage group was higher than that in model group on 7 d, 14 d and 21 d (P＜0.05, P＜0.01). Compared with 0 d, the expression of miR-23a mRNA was increased in the model group and massage group on 21 d, and the expression of miR-23a mRNA in massage group was higher than that in model group (P＜ 0.05).@*CONCLUSION@#Massage can delay the atrophy of denervated skeletal muscle. The mechanism may be related to up-regulation of the expression of miR-23a and Akt mRNA, down-regulation of the expressions of MuRF1 and MAFbx mRNA, inhibition of protein degradation rate, and reduction of skeletal muscle protein degradation.