OBJECTIVE:To observe the effects of total organic acid of Thladiantha dubia fruit(TOATF)on coagulation time and hemorheology of rats with cold coagulation and blood stasis. METHODS:60 rats were randomly divided in normal control group (water),model control group (water),aspirin group (positive drug,50 mg/kg) and TOATF low-dose,medium-dose and high-dose groups(50,100,200 mg/kg)with 10 rats in each group. Except for normal control group,cold coagulation and blood stasis model was induced by 4 ℃ water bath and subcutaneous injection of adrenaline hydrochloride,and then given correspon-dence medicine intragastrically,once a day,for consecutive 14 d. 24 h after last administration,blood samples were collected from aorta abdominalis. The coagulating time(CT),erythrocrit(HCT),plasma viscosity(PV),prothrombin time(PT),thrombin time (TT),activated partial thromboplastin time (APTT),platelet aggregation rate (PAR) and whole blood low-shear,middle-shear and high-shear viscosity were measured and blood sedimentation equation K value was calculated. RESULTS:Compared with nor-mal control group,CT,PT,TT and APTT of model control group were shortened,and HCT,PV,blood sedimentation equation K value,PAR and whole blood low-shear,middle-shear and high-shear viscosity increased(P<0.05 or P<0.01). Compared with model control group,CT,PT and APTT prolonged in aspirin group and TOATF medium-dose and high-dose groups,and PAR de-creased;PT of treatment groups prolonged,while HCT,PV,blood sedimentation equation K value and whole blood low-shear and middle-shear viscosity decreased(P<0.05 or P<0.01). CONCLUSIONS:TOATF has obvious improvement effects on anticoagula-tion and hemorheology in rats with cold coagulation and blood stasis.

Objective To evaluate the efficacy and toxicity of gefitinib on the treatment of advanced NSCLC with brain metastases.Methods 17 cases received gefitinib 250 mg/m2/d,30 days a cycle.Results Objective response rate of 35.3% was achieved,and DCR was 70.6% ,the toxic reactions could be controlled with relative therapy.Conclusion Gefitinib is effective and well tolerable for advanced NSCLC with brain metastases.It is worth to be used.

In recent years, immunotherapy with immune checkpoint inhibitor (ICI) as the representative drug has become an important treatment method for advanced malignant tumors. Preclinical studies have found that disorders of the gut microbiota can reduce the clinical benefit of patients treated with ICI. The latest data indicate that antibiotics may further affect the occurrence and development of tumors and the efficacy of immunotherapy by changing the abundance and composition of intestinal microbiota. To sum up the role of anti-biotics in the immunotherapy of advanced malignant tumor may provide a new idea for the optimization of treatment strategies for patients with advanced cancer.

Aminoglycoside antibiotics, due to their strong antibacterial effects and broad antimicrobial spectra, have been very commonly used in clinical practice in the past half century. However, aminoglycoside antibiotics manifest severe ototoxicity and nephrotoxicity, and are one of top factors in hearing loss. In this study, three members of the aminoglycoside antibiotics family, gentamycin, neomycin and streptomycin, were chosen as the representatives to be investigated for their toxicity to the embryonic development and the larva hair cells in zebrafish, and also to their target genes associated with hearing-related genes. The results showed that: (1) the lethal effect of all three drugs demonstrated a significant dependence on concentration, and the severity order of the lethal effect was streptomycin > neomycin > gentamycin; (2) all the three drugs caused the larva trunk bending in resting state at 5 dpf (day past fertilization), probably due to their ototoxicity in the physical imbalance and postural abnormalities; (3) impairment and reducing of the hair cells were observed in all three cases of drug treatment; (4) four genes, eya1, val, otx2 and dlx6a, which play an important role in the development of hearing organs, showed differential and significant decrease of gene expression in a drug concentration-dependent manner. This study for the first time reports the relevance between the expression of hearing genes and the three ototoxic antibiotics and also proved the feasibility of establishing a simple, accurate, intuitive and fast model with zebrafish for the detection of drug ototoxicity.

Hilar cholangiocarcinoma is one of the most difficult malignant tumors to treat in the biliary system. In Japan, 5-year survival rate of the disease has increased from 32.5% to 67.1% during the past 30 years. The impressive progress reflects the solid efforts in preoperative endoscopic diagnosis, innovation in surgery such as PTPE as well as hepato-pancreatoduodenectomy and perioperative treatment including replacement of the bile and synbiotic treatment, which have finally formed a set of standardized diagnosis and treatment systems. The present review intends to report the history, current status and remaining bottlenecks of the diagnosis and treatment system of hilar cholangiocarcinoma in Japan as follows.

In the treatment of non-small cell lung cancer (NSCLC), immunotherapies represented by immune checkpoint inhibitors are developing rapidly. It is the premise of precise treatment to clarify the influencing factors of NSCLC immunotherapy. In the course of immunotherapy for advanced NSCLC, elderly patients can obtain specific effect from immunotherapy; male patients benefit more from monotherapy; when steroid hormones are used for related symptoms caused by tumors, they are poor prognostic factors for patients. The occurrence of immune-related adverse events is a favorable prognostic factor while driving gene mutations and the use of antibiotics will reduce the efficacy of immunotherapy.

Objective:To evaluate the effects of proton pump inhibitors (PPIs) on the clinical outcomes for advanced solid tumor patients treated with immune checkpoint inhibitors (ICIs).Methods:A total of 204 patients with advanced solid tumors who received ICIs in the Affiliated Hospital of Yangzhou University from November 2016 to December 2020 were retrospectively analyzed. The patients were divided into PPIs group ( n=73) and Non-PPIs group ( n=131) according to whether they received PPIs within 1 month before or after the initiation of ICIs treatment. The correlations between the uses of PPIs and the clinical characteristics of patients were explored, and the clinical efficacy of the two groups was evaluated. Kaplan-Meier survival curve was applied to analyze the effects of PPIs uses on overall survival (OS) and progression-free survival (PFS) of patients. The Cox proportional hazards model was used to clarify whether PPIs was an independent indicator of patients′ prognosis. Results:During ICIs treatment of advanced solid tumors, the use of PPIs was not correlated with the patients′ gender, age, tumor type, the score of the United States Eastern Collaborative Group, types of immunotherapy drugs and treatment strategy (all P>0.05). The objective response rate of the Non-PPIs group was better than that of the PPIs group (45.0% vs. 24.7%, χ2=8.286, P=0.004). The disease control rate of the Non-PPIs group was better than that of the PPIs group (75.6% vs. 52.0%, χ2=11.755, P=0.001). In patients with advanced solid tumors, the median OS (3.4 months vs. 6.1 months) and median PFS (2.8 months vs. 4.0 months) in the PPIs group were shorter than those in the Non-PPIs group ( χ2=9.563, P=0.002; χ2=5.761, P=0.016). Univariate analysis showed that among patients with advanced solid tumors treated with ICIs, PPIs uses was significantly correlated with OS ( HR=1.85, 95% CI: 1.24-2.76, P=0.003); PPIs uses( HR=1.65, 95% CI: 1.09-2.51, P=0.019) and age ( HR=1.56, 95% CI: 1.05-2.32, P=0.029) were significantly correlated with PFS. Multivariate analysis showed that PPIs uses was an independent prognostic factor affecting OS ( HR=1.90, 95% CI: 1.27-2.85, P=0.002) and PFS ( HR=1.73, 95% CI: 1.12-2.65, P=0.013). Meanwhile, subgroup analysis discovered that in the course of ICIs treatment of lung cancer patients, the median OS (3.2 months vs. 6.2 months) and median PFS (2.2 months vs. 3.8 months) in the PPIs group ( n=64) were shorter than those in the Non-PPIs group ( n=34) ( χ2=16.187, P<0.001; χ2=5.106, P=0.020). Univariate analysis showed that PPIs uses was associated with OS ( HR=2.97, 95% CI: 1.70-5.22, P<0.001) and PFS ( HR=1.97, 95% CI: 1.09-3.55, P=0.025) in lung cancer patients treated with ICIs. Multivariate analysis showed that PPIs uses was an independent prognostic factor for OS ( HR=3.38, 95% CI: 1.87-6.11, P<0.001) and PFS ( HR=2.31, 95% CI: 1.22-4.38, P=0.010) in lung cancer patients treated with ICIs. Conclusion:The use of PPIs reduces the effect of ICIs in the treatment of advanced solid tumor, especially in lung cancer. PPIs should be used cautiously in patients with advanced solid tumors treated with ICIs.

Objective To identify the morphology of arsenic in drinking water,by detecting arsenic in the drinking water within the endemic areas so as to determine the causes of arsenic through different forms of arsenic exposure.Methods The arsenic poisoning area and the high arsenic arsenic area in Taonan City and Tongyu County of Jilin Province were selected as the survey sites.The drinking water samples were collected,and the arsenic content and different arsenic species in the water samples were measured and analyze the relationship between well depth and water arsenic content.Resets A total of 161 arsenic water samples were tested,mainly in the form of inorganic arsenic;As5+ concentration was 0.004 to 0.226 mg/L,the median was 0.053 mg/L;the As3+ concentration was 0.004 to 0.309 mg/L,the median was 0.057 mg/L.Total arsenic content was in the range of 0.009 to 0.509 mg/L,the median was 0.100 mg/L.Monomethylated arsenic (MMA) was detected in 1 water sample with the content of 0.005 mg/L,dimethyl arsine (DMA) was detected in 1 water sample with the content of 0.014 mg/L.Totally 101 wells were surveyed with the depth of 13 to 75 meters.Totally 94 water samples had the water arsenic level of more than 0.05 mg/L,and most of them were detected in the well with the depth of more than 50 meters,which was accounted for 85.1％ (80/94).Conclusions Arsenic mainly exists in the form of inorganic arsenic in drinking water,organic arsenic is only found in water at low concentrations.Excessive water arsenic is mainly distributed in wells deeper.

Objective By comparing biomechanical properties of two-screw rod and three-screw rod for fixing pelvic fracture, the difference in mechanical effects of different screw rod fixation positions in pelvic minimally invasive surgery was studied.Methods The mechanical models of pelvis fixed by two-screw rod and three-screw rod were established, and biomechanical characteristics of the pelvis during standing on both legs, during single-legged standing on healthy side or affected side, as well as in sitting posture were compared and analyzed by finite element simulation, and the fixation effect of three-screw rod was verified by clinical experiments.Results Both fixation methods could restore mechanical transmission of the pelvis. But for three-screw rod fixation, the stress on both sides of the pelvis was more balanced, and the displacement of the whole body and fracture surface was also lower during single-legged standing.Conclusions The three-screw rod fixation has an excellent effect in stability, which is more beneficial for fracture recovery.

Objective To study the urinary arsenic safety guideline value of a population for evaluating the arsenic exposure level in a certain population and providing evidence for the implementation of prevention and control measures in endemic arsenicosis area.Methods According to the data from the national high-arsenic drinking water sources screening in endemic arsenicosis area of drinking water type and quality supervision and inspection for water-improving project to decrease arsenic from 2005 to 2014,census data on arsenic poisoning in endemic arsenicosis area,data on surveillance of endemic arsenicosis,10 722 people with detailed personal information,complete water arsenic exposure data and accurate urinary arsenic detection data were selected to be the research objects.The relationship between urinary arsenic and water arsenic was analyzed based on the surveillance data of 4 501 people from 2013 to 2014.The safety guidance value of urinary arsenic was determined based on the geometric mean value of urinary arsenic in people exposed to water arsenic in the range of (0.050 ± 0.005) mg/L,and verified using the data of 6 221 people from 2005 to 2012.Every time,a random sample of 2 000 people was taken as the verification sample,the sensitivity and specificity of the index for determining whether water arsenic exposure exceeded the standard were determined by area under the ROC curve (AUC),and a total of 10 sample tests was performed.Results When the water arsenic concentration was less than 0.01 mg/L,the correlation coefficient of water arsenic concentration with urinary arsenic concentration was 0.097 (P ＜ 0.01);when the water arsenic concentration was more than 0.01 mg/L and less than 0.05 mg/L,the correlation coefficient of arsenic concentration with water arsenic concentration was 0.456 (P ＜ 0.01);when the water arsenic concentration was more than 0.05 mg/L,the correlation coefficient of water arsenic concentration with urinary arsenic concentration was 0.630 (P ＜ 0.01).With increase of water arsenic concentration,the concentration of urinary arsenic increased significantly,and the difference was statistically significant (x2 =2 337.956,P ＜ 0.01).When water arsenic concentration was in the range of (0.050 ± 0.005) mg/L,the urinary arsenic geometric mean was 0.032 mg/L.AUC analysis of 10 random samples of 2 000 people showed that the geometric mean of urinary arsenic was 0.032 mg/L in the population,which can accurately distinguish whether the water arsenic level exceeded 0.05 mg/L,and the AUC value was higher than 0.94.And the sensitivity and specificity were achieved 0.898 and 0.844.Conclusions The geometric mean of urinary arsenic is 0.032 mg/L,which can be used as a safety guideline value for urinary arsenic in the population.When the geometric mean of urinary arsenic exceeds this value,the population may be exposed to high arsenic.