In the past two decades,with the increase of smoking population,more and more people are suffering from small cell lung cancer(SCLC).Besides,it is difficult to find an effective way to cure SCLC,since patience can easily develop drug resistance.On the other hand,with the development of science and technology,people began to study the anti-cancer strategy to increase apoptosis,such as inhibiting the overexpression of survival factors.In these survival factors,BCL-2 family has attracted a lot of attention.BH3-only protein is a member of BCL-2 family and it can directly inhibit the expression of BCL-2 protein,thereby prompting apoptosis.Since the BH3-only protein itself is difficult to become a clinical drug, to find alternatives BH3-only protein-BH3 mimetics is particularly important. Plus, more and more researchers have paid attention on the natural BH3 mimetic since it has less side-effect than artificial BH3 mimetics.To find possible BH3 mimetics,we made a primary screening with this pharma-cophore on a small molecular compounds library via Discovery Studio software. And then MTS assay were introduced to verify the activity of compounds. After that, we use Western Blot and Co-IP meth-ods to test the effect of BH3 mimetics.And finally use CDOCKER to predict the further mechanism on autophagy and apoptosis.In our studies, we found 3 possible BH3 mimetics compounds from 170,000 natural small molecular compounds via pharmacophore-based virtual screening.Furthermore,we dem-onstrated AD23,one of the 3 possible natural BH3 mimetics,induced autophagy and apoptosis simulta-neously in dose-time dependence in SCLC cell line. Finally, we use Molecular Docking to predict the further mechanism on autophagy and apoptosis. We believe our works would provide evidences and clues for the structural optimizing and further study of new drugs in the future.

Pancreatic ductal adenocarcinoma (PDAC) is one of the five most malignant cancer. ZX-1201 is one of the active constituents in Alismatis Rhizoma,a well-known traditional Chinese medi-cine with a wide variety of pharmacological properties including diuretic,anti-hyperlipidemic,anti-atheroscle-rotic,anti-cancer,anti-inflammatory and anti-oxidative activities.We investigated the inhibitory effect of ZX-1201 on pancreatic cancer and the relevant molecular mechanism in vitro and in vivo. ZX-1201 inhibited the growth and metastasis of PANC-1 cells in BALB/c nude mice significantly.ZX-1201 inhibited the function of AQP1 via directly interaction and involved in the reversion process of ZX-1201 on TGF-β1. CTGF was an important protein in the reversion process of ZX-1201 on TGF-β1.ZX-1201 inhibited the migration of PANC-1 and CPFAC-1 cells induced by TGF-β1in vitro.ZX-1201 reversed the down-regu-lated of epithelial markers and up-regulated of mesenchymal markers, as well as the up-regulated of Snail and p-Smad2/3 induced by TGF-β1.And ZX-1201 reversed Epithelial-Mesenchymal Transition by down-regulating AQP1 and inhibiting translocation of β-catenin, the promotor of CTGF. According to these,ZX-1201 inhibited the migration of pancreatic cancer cells.We concluded that ZX-1201 inhibited the growth and metastasis of PANC-1 cells in vivo significantly.And AQP1,β-catenin and CTGF were the pivotal proteins in the process of ZX-1201 inhibiting PANC-1 cells migration induced by TGF-β1.

Objective To investigate the number and distribution of un-repaired cleft lip/palate patients in Gansu province. Methods A census was conducted by staff members of the health system and Population and Family Planning Committee (PFPC) in Gansu province. Standardized -Questionnaires were administered to collect demographic, domestic and diagnosis-related information. Results In 2008, the total number of un-repaired cleft lip/palate patients was 4675,with a detection rate of 1.84/10 000 in Gansu province. Rates of detection were higher in males (2.11/10 000), young age group(4.86/10 000), rural areas(2.23/10 000),poor counties(2.19/10 000)than in females(1.43/10 000), medium (0,97/10 000)/old age group(0.68/10 000), township areas (0.62/10 000), or richer counties (1.35/10 000). Among all the cities and prefectures of Gansu,Baiyin city (2.7/10 000) had the highest while Jinchang city (0.7/10 000) had the lowest prevalence rates. Conclusion Un-repaired cleft lip/palate had been a disease burden to Gansu province,especially in the rural area and poorer counties.

Objective To evaluate the value of serum CEA and CA19-9 concentration for clinical staging of colorectal cancer. Methods A total of 350 patients who underwent the surgical treatments for colorectal cancer between February 2015 to January 2017 were enrolled. The serum CEA and CA19-9 were detected by chemoluminescence method. Results The positive rate of CEA of patients in stageⅠto Ⅳ was 25.00%, 36.69%, 50.78% and 66.67%, respectively. The positive rate of CA19-9 of patients in stageⅠto Ⅳwas 2.94%, 10.07%, 17.97% and 53.33%, respectively. The positive rates of CEA and CA19-9 were gradually increased with the stage developing (P<0.05). Results from multivariate logistic regression analysis showed that the positive levels of CEA and CA19-9 were risk factors in the TNM staging of colorectal cancer. The ORs and 95%CI were 1.790 (1.163-2.755)and 3.476(1.790-6.749), respectively. Conclusion The positive serum concentrations of CEA and CA19-9 showed significant associations with TNM staging. Preoperative serum concentrations of CEA and CA 19-9 could be auxiliary diagnostic indicators to assess the condition of colorectal cancer.

OBJECTIVETo investigate the selectivity and individualization of transpedicular balloon kyphoplasty for aged osteoporotic spinal fracture.

METHODSTwenty-two consecutive procedures were performed in 17 aged patients with osteoporotic spinal compression fractures from April 2002 to June 2004. The signal changes in different sequences were confirmed by magnetic resonance imaging before the procedures. This operation involved the percutaneous insertion of two inflatable bone tamps into a fractured vertebral body transpedicularly under fluoroscopic guidance. Every patient was treated individually, according to the results of radiography and CT scan before operation. Preoperative and postoperative complications, visual analogue scale, and radiographic findings such as vertebral height and Cobb angle were recorded and analyzed.

RESULTSAll patients tolerated the procedure well with immediate relief of their back pain in 24 hours. There was no leakage of cement into the epidura. The mean loss percent of the anterior and middle vertebral heights were (35.32 +/- 13.15)% and (27.53 +/- 12.61)% before operation, and (14.21 +/- 12.43)% and (16.2 +/- 7.5)% after operation. The height restoration of vertebra was confirmed by X-ray after the procedure (P < 0.01). The mean kyphosis was improved from (25.3 +/- 4.2) degrees to (8.6 +/- 5.1) degrees. No complications occurred. No patient had nerve injury. The patients were allowed to walk next day after the procedure.

CONCLUSIONThe selectivity and individualization of transpedicular balloon kyphoplasty for aged osteoporotic spinal fractures has satisfactory short-term clinical efficacy. It is also an effective way to prevent complications.

Aged ; Aged, 80 and over ; Female ; Fracture Fixation, Internal ; methods ; Fractures, Spontaneous ; etiology ; surgery ; Humans ; Kyphosis ; etiology ; surgery ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; methods ; Osteoporosis ; complications ; Osteoporosis, Postmenopausal ; complications ; Spinal Fractures ; surgery

OBJECTIVETo contrast single and double balloon-inflated kyphoplasty for vertebral compression fractures (VCFs) and evaluate its clinical efficacy.

METHODSFrom May 2000 to May 2004, 90 consecutive procedures were performed in 58 patients who suffered from painful vertebral compression fractures, transferring tumour and angioma. Ninety vertebrae were inflated while 62 as A group were double balloon and 28 as B group were single balloon, fracture reduction and bone cement augmentation. Preoperative and postoperative symptom levels, variables, complications were recorded and the vertebral height and Cobb angle were measured and analyzed.

RESULTSAll patients' pain was alleviated or disappeared without syndrome, and the vertebral height and Cobb angle of both groups were improved. The average recovery rate was 72.6% (22.9% approximately 100%), Cobb angle from 17.9 degrees (3.1 degrees approximately 31.6 degrees ) were corrected to 9.6 degrees (0.6 degrees approximately 28.2 degrees ), the average angle was 8.7 degrees (0.3 degrees approximately 27.2 degrees ), and the contrast between preoperative and postoperative showed obvious differences (P <0.001). The average recovery rate of A group was 77.6% (55.3% approximately 100%), B group was 64.3% (22.9% approximately 100%). The average postoperative Cobb angle of A group was 9.9 degrees (0.3 degrees approximately 27.2 degrees ), B group was 8.6 degrees (0.6 degrees approximately 19.8 degrees ) (P >0.05).

CONCLUSIONSAs a promising minimally invasive surgery, balloon kyphoplasty can provide early relief of pain and improve the function as well as spinal alignment in treatment of painful compression fracture owing to recovering the vertebral height and Cobb angle of the vertebral body. Single balloon-inflated kyphoplasty can improve VCFs as double balloon.

Adult ; Aged ; Aged, 80 and over ; Bone Cements ; therapeutic use ; Female ; Fractures, Compression ; complications ; surgery ; Humans ; Kyphosis ; etiology ; surgery ; Lumbar Vertebrae ; injuries ; surgery ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; Orthopedic Procedures ; instrumentation ; methods ; Retrospective Studies ; Spinal Fractures ; complications ; surgery ; Thoracic Vertebrae ; injuries ; surgery

OBJECTIVEThe purpose of this study was to analyze the electrocardiographic features of the people living in the area with high incidence of unexplained sudden deaths in Yunnan province.

METHODThe electrocardiograms of 338 residents from three villages (Dayao, Ninglang, Heqing) with high incidence of unexplained sudden deaths and one control village (Dali) were analyzed [averaged age was (33.4 +/- 11.7) years, 175 men and 163 women].

RESULTSThe incidence of cardiac arrhythmias was similar low in all groups. The left ventricular hypertrophy was observed in 34.6% of residents from Dayao. QTc significantly prolonged in the residents from all 3 high incidence areas compare the control area of Dali [control (386.8 +/- 27.22) ms, Ninglang (428.92 +/- 25.71) ms, Heqing (440.67 +/- 28.03) ms, Dayao (417.7 +/- 24.00) ms, P < 0.05 vs. control]. Incidence of U wave was significantly higher in Heqing village than that in control village (P < 0.05). The QUc of these 3 villages was: (613.67 +/- 37.34) ms, (597.19 +/- 46.47) ms, (608.59 +/- 39.59) ms respectively, and also significantly longer than the control village of Dali (589.33 +/- 41.27) ms (P < 0.05). The typical pattern of U wave presents as enlarged U wave and apparent T-U complex. In the 7 residents who have the family history of unexplained sudden death, 6 residents have U wave, and 4 of them present typical U wave pattern.

CONCLUSIONThe significant ECG changes in villages with high incidence of unexplained sudden death in Yunnan province were prolonged QTc, enlarged U wave and apparent T-U complex and these ECG features suggested the repolarization abnormalities of the heart in these subjects.

Adolescent ; Adult ; China ; epidemiology ; Death, Sudden ; epidemiology ; etiology ; Electrocardiography ; statistics & numerical data ; Female ; Humans ; Long QT Syndrome ; physiopathology ; Male ; Mass Screening ; Middle Aged ; Young Adult

From the perspective of data users, ensuring the relevance and reliability of big data in healthcare and medicine via assessments on data appropriateness is a prerequisite for generating high-quality real-world evidence, which could guarantee good representativeness and generalizability of real-world studies. This review summarized the quality dimensions, definitions, evaluation indexes and calculating methods of assessment on the appropriateness of real-world data (RWD) according to guidance from different countries and international organizations, as well as exploring the opportunities and challenges for better assessing RWD appropriateness.
Big Data ; Delivery of Health Care ; Humans ; Reproducibility of Results

Aim To explore the potential genes and mechanism of alisol B in the treatment of non-small cell lung cancer(NSCLC).Methods The proliferation and migration of NSCLC cells were detected by CCK-8 and Transwell.Genes of NSCLC and alisol B were col-lected through TCGA and compound gene prediction database,and their intersection genes were obtained.The network of protein-protein interaction(PPI)was constructed by using String database,and the top 20 key nodes were screened out,and the prognosis-related proteins related to the prognosis of NSCLC were screened out by using R language,and the intersection of them was obtained.The potential mechanism of ali-sol B on NSCLC was explored by KEGG and GO en-richment analysis and the relationship between related genes and immune cells,which was verified by cell-lev-el experiments.Results Alisol B inhibited the cell activity and migration ability of NSCLC cells.Five im-portant genes were identified by network pharmacologi-cal analysis:CCNE1,CDK1,COL1A1,COL1A2 and COL3A1.The results of cell experiment showed that al-isol B down-regulated the expression of Cyclin E1,CDK1 and COL1A2 in NSCLC cells.In addition,alisol B could inhibit the expression of COL1A2 and M2 macrophage marker CD206 in macrophages.Conclu-sions Alisol B may inhibit the proliferation of tumor cells by down-regulating CDK1 and Cyclin E1,and may affect the function of macrophages by inhibiting COL1A2,thus regulating the tumor immune microenvi-ronment and inhibiting NSCLC.

OBJECTIVE: To evaluate the association between serum uric acid (SUA) and kidney function decline. METHODS: Data was obtained from the China Health and Retirement Longitudinal Study on the Chinese middle-aged and older population for analysis. The kidney function decline was defined as an annual estimated glomerular filtration rate (eGFR) decrease by > 3 mL/min per 1.73 m ². Multivariable logistic regression was applied to determine the association between SUA and kidney function decline. The shape of the association was investigated by restricted cubic splines. RESULTS: A total of 7,346 participants were included, of which 1,004 individuals (13.67%) developed kidney function decline during the follow-up of 4 years. A significant dose-response relation was recorded between SUA and the kidney function decline ( OR 1.14, 95% CI 1.03-1.27), as the risk of kidney function decline increased by 14% per 1 mg/dL increase in SUA. In the subgroup analyses, such a relation was only recorded among women ( OR 1.22, 95% CI 1.03-1.45), those aged < 60 years ( OR 1.22, 95% CI 1.05-1.42), and those without hypertension and without diabetes ( OR 1.22, 95% CI 1.06-1.41). Although the dose-response relation was not observed in men, the high level of SUA was related to kidney function decline ( OR 1.83, 95% CI 1.05-3.17). The restricted cubic spline analysis indicated that SUA > 5 mg/dL was associated with a significantly higher risk of kidney function decline. CONCLUSION The SUA level was associated with kidney function decline. An elevation of SUA should therefore be addressed to prevent possible kidney impairment and dysfunction.
Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; East Asian People ; Glomerular Filtration Rate ; Kidney/physiopathology* ; Longitudinal Studies ; Risk Factors ; Uric Acid/blood*