Multidrug resistance (MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein (P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent, specific, and orally active P-gp inhibitor. Through direct binding to P-gp, WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel (PTX) in multiple resistant cell lines, without changing its expression or subcellular localization. WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid, induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells. In addition, WS-716 displayed minimal effect on the drug-metabolizing enzyme cytochrome P4503A4 (CYP3A4). Importantly, WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7% in patient-derived xenograft (PDX) models. Relative to PTX treatment alone, combination of WS-716 and PTX caused no obvious adverse reactions. Taken together, our preclinical studies revealed therapeutic promise of WS-716 against MDR cancer, the promising data warrant its further development for cancer therapy.

Objective: To investigate the role of inflammatory biomarkers in the relationship between blood lead levels and blood pressure changes. Methods: A total of 9 910 people aged 18-79 years who participated in the China National Human Biomonitoring in 2017-2018 were included in this study. A self-made questionnaire was used to collect demographic characteristics, lifestyle and other information, and the data including height, weight and blood pressure were determined through physical examination. Blood and urinary samples were collected for the detection of blood lead and cadmium levels, urinary arsenic levels, white blood cells, neutrophils, lymphocytes, and hypersensitive C-reactive protein (hs-CRP). Weighted linear regression models were used to evaluate the associations between blood lead, inflammatory biomarkers and blood pressure. Mediation analysis was performed to investigate the role of inflammation in the relationship between blood lead levels and blood pressure changes. Results: The median (Q₁, Q₃) age of all participants was 45.4 (33.8, 58.4)years, including 4 984 males accounting for 50.3%. Multivariate logistic regression model analysis showed that after adjusting for age, gender, residence area, BMI, education level, smoking and drinking status, family history of hypertension, consumption frequency of rice, vegetables, and red meat, fasting blood glucose, total cholesterol, triglycerides, blood cadmium and urinary arsenic levels, there was a positive association between blood lead levels, inflammatory biomarkers and blood pressure (P<0.05). Each 2.71 μg/L (log-transformed) increase of the lead was associated with a 2.05 (95%CI: 0.58, 3.53) mmHg elevation in systolic blood pressure (SBP), 2.24 (95%CI: 1.34, 3.14) mmHg elevation in diastolic blood pressure (DBP), 0.25 (95%CI: 0.05, 0.46) mg/L elevation in hs-CRP, 0.16 (95%CI: 0.03, 0.29)×10⁹/L elevation in white blood cells, and 0.11 (95%CI: 0.02, 0.21)×10⁹/L elevation in lymphocytes, respectively. Mediation analysis showed that the levels of hs-CRP significantly mediated the association of blood lead with SBP, with a proportion about 3.88% (95%CI: 0.45%, 7.32%). The analysis also found that the levels of hs-CRP and neutrophils significantly mediated the association of blood lead with SBP, with a proportion about 4.10% (95%CI: 1.11%, 7.10%) and 2.42% (95%CI: 0.07%, 4.76%), respectively. Conclusion: This study suggests that inflammatory biomarkers could significantly mediate the association of blood lead levels and blood pressure changes.
Adult ; Male ; Humans ; Blood Pressure/physiology* ; C-Reactive Protein/analysis* ; Lead ; Arsenic/analysis* ; Cadmium ; Biomarkers ; Hypertension/epidemiology* ; China/epidemiology*

ARNTL Transcription Factors ; deficiency ; metabolism ; Animals ; Cyclic AMP ; metabolism ; Gluconeogenesis ; Glucose ; biosynthesis ; HEK293 Cells ; Histone Deacetylases ; metabolism ; Humans ; Liver ; metabolism ; Mice ; Mice, Knockout

Background: Esophageal cancer is associated with substantial disease burden in China, and data on the economic burden are fundamental for setting priorities in cancer interventions. The medical expenditure for the diagnosis and treatment of esophageal cancer in China has not been fully quantified. This study aimed to examine the medical expenditure of Chinese patients with esophageal cancer and the associated trends. Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 37 hospitals in 13 provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. For each esophageal cancer patient diagnosed between 2002 and 2011, clinical information and expense data were extracted by using structured questionnaires. All expense data were reported in Chinese Yuan (CNY; 1 CNY= 0.155 USD) based on the 2011 value and inflated using the year-specific health care consumer price index for China. Results: A total of 14,967 esophageal cancer patients were included in the analysis. It was estimated that the overall average expenditure per patient was 38,666 CNY, and an average annual increase of 6.27％ was observed from 2002 (25,111 CNY) to 2011 (46,124 CNY). The average expenditures were 34,460 CNY for stage Ⅰ, 39,302 CNY for stage Ⅱ, 40,353 CNY for stage Ⅲ, and 37,432 CNY for stage IV diseases (P < 0.01). The expenditure also differed by the therapy type, which was 38,492 CNY for surgery, 27,933 CNY for radiotherapy, and 27,805 CNY for chemotherapy (P < 0.05). Drugs contributed to 45.02％ of the overall expenditure. Conclusions: These conservative estimates suggested that medical expenditures for esophageal cancer in China substantially increased in the last 10 years, treatment for early-stage esophageal cancer costs less than that for advanced cases, and spending on drugs continued to account for a considerable proportion of the overall expenditure.

?AlM: To investigate the outcome and safety of Ahmed glaucoma valve implantation treatment in uncontrolled primary congenital glaucoma ( PCG) .
? METHODS: Twenty - two eyes in 22 children with uncontrolled PCG were reviewed retrospectively and underwent Ahmed glaucoma valve implantation treatment from January 2011 to December 2014. Main checking index included intraocular pressure ( lOP ) before and after operation, corneal diameter and complications.
?RESULTS: Preoperative mean age was 3. 74±2. 24y, and 2. 59 ± 1. 78y apart from the last operation. Postoperative average lOP was 35. 22 ± 6. 36mmHg. Average corneal diameter was 12. 79 ± 0. 75mm. Mitomycin C ( 0. 3 - 0. 5mg/mL ) was used in all operations for 3-5min. Glaucoma valves were implanted in the temporal or nose above the equator sclera. Postoperative lOP was 11. 4±4. 45mmHg at 1wk, and 16. 73± 7. 23mmHg after 12mo. As lOP< 21mmHg for success criteria, lOP of 16 eyes ( 73%) were controlled after 12mo. Preoperative 6 cases had shallow anterior chamber, recovered spontaneously. No serious complication was recorded, such as rejection of glaucoma valve, endoophthalmitis and corneal decompensation.
?CONCLUSlON:Ahmed glaucoma valve implantation in uncontrolled PCG is a safe and viable treatment.

Bombyx mori nucleopolyhedrovirus (BmNPV) bm47 gene is found in all sequenced lepidopteran nucleopolyhedroviruses (NPVs). It is one of the core genes of NPVs. However, the role of bm47 in the biological cycle of NPV remains unknown. In this study, the Red recombination system was used to knock out bm47 from BmNPV to construct bm47-ko-Bacmid in E. coli BW25113 system. Then bm47 gene was introduced back to the viral genome using the Bac-to-Bac system to create the repair virus bm47-re-Bacmid. TCID50 assay and real-time PCR (qPCR) were used to evaluate the effects of bm47 deletion on viral DNA replication, gene transcription, and protein expression. qPCR results showed that bm47 knock-out had no significant effect on viral DNA replication. However, the qPCR results showed that bm47-ko-Bacmid significantly decreased the transcription levels of early gene lef-3, late gene vp39, and very late gene p10 at 48 h and 72 h after viral transfection of BmN cells (P < 0.05). This work will provide a foundation for further studies on the biological function of BmNPV bm47 in viral replication and transcription.
Animals ; Bombyx ; virology ; Gene Deletion ; Gene Expression Regulation, Viral ; Nucleopolyhedrovirus ; genetics ; physiology ; Transcription, Genetic ; Viral Proteins ; genetics ; metabolism ; Virus Replication

Objective To investigate the relations between training and both the attitude and practice on smoking control among community medical staff members in Hangzhou,Zhejiang province.Methods Three representative districts including Xiacheng,Gongshu and Westlake were chosen from Hangzhou city.Questionnaire survey was applied to collect information from the related community medical staff members.The survey mainly contained three aspects:knowledge,attitude and practice regarding smoking control involved in the community medical activities.Availability and application of the resources on smoking cessation were also studied.Logistic regression analysis was applied to explore the factors associated with the smoking control training programs.Differences of rates between groups were assessed with chi-square statistics.Wilcoxon rank sum test was used to study the relationships among knowledge,attitude and practice related to smoking control programs,targeted to the community medical staff members.Results Eight hundred forty-six community medical workers were involved.Sixty-five percent of the community medical staff members had learned related knowledge on smoking control.Proportion of the community medical staff who had taken lessons on smoking control with 3-10 working years was 1.77 times more than the ones with experience less than two years (OR=1.77,95％CI:1.25-2.51).Eighty-eight point seven percent of the medical staff who had received smoking control training programs were identified with the consciousness that they should advise the patients to quit smoking,comparing to the proportion 81.60％ (Z=-2.87,P=0.00) in the control group.In terms of the practice regarding smoking control,data showed that 21.62％ of the medical staff who had received smoking control training programs would provide ‘how to quit smoking' to more than 90％ of the smoking patients,while the proportion in the control group was 10.65％ (Z=-5.68,P=0.00).The use of drugs,traditional Chinese medicine therapy and the smoking cessation hotline rate were all less than 30％.Conclusion The training programs being used on smoking control seemed useful in improving the consciousness and practice towards the smoking control programs during their medical activities among the community medical staff members.

DNA, Bacterial ; genetics ; Humans ; Molecular Typing ; Neisseria meningitidis, Serogroup B ; classification ; genetics

OBJECTIVETo study the metastasis and micrometastasis in No.14v lymph nodes in patients with lower third gastric cancer.

METHODSA retrospective study was performed. A total of 53 patients undergoing radical resections by a single surgeon for lower third gastric cancer in the Department of General Surgery at the Affiliated Hospital of Qingdao Medical College were included. Conventional pathological section was used to detect lymph nodes metastasis and telomere TRAP-ELISA was used to identify the micrometastasis in No.14v lymph nodes.

RESULTSA total of 96 lymph nodes were dissected from the No.14v group and lymph nodes metastasis were discovered in 9 patients by conventional pathological section. Forty-four patients had no metastasis on conventional pathological examination, of whom 13(29.6%) were found to have micrometastasis. The overall metastatic rate was 41.5%(22/53). Metastasis and micrometastasis in the No.14v lymph nodes were associated with Borrmann types, depth of invasion, No.6 lymph nodes metastasis, tumor diameter, and TNM staging(P<0.05).

CONCLUSIONSNo.14v lymph nodes in patients with lower third gastric cancer is associated with a high incidence of metastasis and micrometastasis. The status of No.6 lymph nodes may be used as an useful indicator for No.14v lymph nodes metastases during the operation.

Adult ; Aged ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; pathology ; Male ; Middle Aged ; Neoplasm Micrometastasis ; pathology ; Retrospective Studies ; Stomach Neoplasms ; pathology ; surgery

ObjectiveEvidence-based medicine was used to make an individualized treatment plan for rare solitary splenic metastasis of an ovarian carcinoma in a female patient. MethodsAfter clinical problems were discovered, evidence was collected from the Cochrane Library, PubMed, EMBASE, ScienceDirect, CNKI and Wanfang databases according to our predefined search strategy. The search was done until October, 2009. The validity of the evidence was assessed. The evidence, combined with the doctor experience and the patient value, was applied to the patient. ResultsA total of 15 English literature and 11 Chinese literature were identified. A rational treatment plan was made upon a critical evaluation of the data. There were 5 review articles in PubMed, EMBASE and ScienceDirect databases and no RCT in the Cochrane Library. And there was one retrospective cohort study inCNKI and Wanfang databases. The others were all case reports. After 20 month follow-up, the treatment protocol was proven correct. Conclusion The patient has rare disease, and the evidence intension for the evidence-based medicine was low. It can not present the efficacy of the evidence-based medicine treatment sufficiently, though it could provide some suggestion for rare disease which was lack of large RCT for evidence-based Methods .