Objectives:To investigate the association between social determinants of health(SDOH)and incident stroke and analyze the main risk factors for stroke among resident with different SDOH levels. Methods:From 2012 to 2015,30 036 residents(≥35 years old)from 30 districts in 14 provincial-level administrative divisions in China were enrolled this study based on stratified multi-stage-random-sampling method.The prevalence of cardiovascular diseases and related risk factors were investigated,and stroke events were followed up in 2018 to 2019.Principal component analysis was performed to establish SDOH scores based on 9 indicators related to socioeconomic and healthcare resources,participants were divided into low SDOH group(n=8 343)when it was≥-2.01 to<-1.14,middle SDOH group(n=7 257)when it was≥-1.14 to<0.10,and high SDOH group(n=8 457)when it was≥0.10 to≤5.79.Multivariate Cox regression was applied to estimate the association of SDOH levels with incident stroke.The random survival forest method was used to analyze the major risk factors in different SDOH levels. Results:A total of 24 057 participants were finally included,669(2.8%)participants developed stroke during a mean of(4.7±0.8)years follow-up.The incidence densities of stroke in the low,medium,and high SDOH groups were 468.39,628.85,and 700.39/100 000 person-years,respectively(Pdifference<0.05,Ptrend=0.01).Compared with individuals with low SDOH level group,fully HR for incident stroke among those with medium and high were 1.91(95%CI:1.54-2.36)and 1.59(95%CI:1.30-1.95),respectively(Ptrend<0.001).Advanced age is the primary risk factor for stroke in the population,especially in districts with high SDOH level.In districts with medium SDOH level,diabetes is an important risk factor for stroke.High blood pressure and alcohol consumption are important modifiable risk factors in low SDOH level districts. Conclusions:Present study shows that higher levels of SDOH are associated with increased risk of stroke.The main risk factors for stroke differ among participants with different SDOH level districts.Targeted interventions should be implemented to improve the prevention and treatment of stroke in populations with different levels of SDOH.

Purpose To design PCR combined probes u-sing TaqMan technology to detect the expression of major driver genes in a variety of soft tissue sarcomas at one time,and to dis-cuss whether the combined probes can better assist clinicopatho-logical diagnosis based on histological features and FISH results.Methods Our research group designed 32 pairs of fusion gene probes related to soft tissue sarcoma based on TaqMan tech-nique,involving 10 types of sarcoma.The histopathological specimens of 70 patients with common fusion gene soft tissue sarcoma in our hospital were examined by fusion gene combina-tion,and the histopathological specimens of 30 patients with oth-er soft tissue sarcoma without fusion gene were set as controls.Individual common sarcoma types were analyzed with FISH probe detection.At the same time,the detection performance of the combined probe was evaluated by various methods.Results The soft tissue sarcoma-related fusion gene probe designed by our research group was used to detect the confirmed soft tissue sarcomas,and the results showed that the highest sensitivity was 100％.Among the three types of tumors,protuberant dermatofi-brosarcoma,synovial sarcoma and mucinous liposarcoma were verified by FISH,and the coincidence rate of the two methods was high,with no statistical significance(P＞0.05).The re-sults of interlot and intralot reproducibility of protuberous derma-tofibrosarcoma,mucinous liposarcoma and synovial sarcoma were consistent.Three different concentration limits were used to de-tect the positive plasmid of all the fused gene RNA,and 25 cop-ies/μL was the lowest concentration limit.Conclusion Com-bined with the pathological diagnosis results,TaqMan technology can be used to design PCR combined probes for soft tissue sarco-ma,which have high sensitivity and high specificity and good methodological performance,and meet the needs of primary medical institutions for one-time and rapid auxiliary pathological diagnosis of common soft tissue sarcoma.It provides a rapid and reliable method for the detection of multiple fusion genes in clin-ical soft tissue sarcoma.

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.

Objective: To investigate the safety and efficacy of fluorouracil-based two-drug combination chemotherapy with apatinib, as a conversion therapy, in patients with unresectable gastric cancer (GC). Methods: A retrospective analysis of 33 patients with unresectable stage IV GC receiving conversion therapy at Tianjin Medical University Cancer Institute and Hospital between March 2017 and June 2018, was performed. Patients with peritoneal or ovarian metastasis received S1/paclitaxel (PTX)/apatinib (S1: 60 mg, bid, days 1-14; PTX: 50 mg/m2 iv, days 1 and 8; PTX: 20 mg/m2 ip, days 1 and 8; q3w; apatinib 500 mg po, qd). Patients with other non-curable factors were administered a regimen of SOX plus apatinib (oxaliplatin 130 mg/m2, S1: 60 mg, bid, days 1-14; apatinib 500 mg po, qd). Apatinib should be withdrawn from the last cycle before surgery. Surgery should be performed after MDT. Results: After at least three cycles chemotherapy, 21 patients achieved partial response (PRand 8 patients had progressive disease (PD), resulting in an objective response rate of 75.7%. Surgery was performed on 22 patients with PR, and 21 patients (63.6%) achieved R0 resection; the number of excised lymph nodes was 57.0±15.6, intraoperative hemorrhage was (164±46) mL, the operation time was (212.0±44.8) min, and the postoperative hospital stay was (13.0±2.7) days. Patients who had surgery had a median progression free survival (mPFS) of 10.5 months and an median overall survival (mOSof 16.5 months; for patients who did not undergo surgery, the median progression free survival (mPFSwas 2.5 months and mOS was 5.5 months. Conclusions: As a conversion therapy, fluorouracil-based two drug-combination chemotherapy with apatinib provided a high R0 resection rate for unresectable stage GC, with an acceptable safety profile. Keywords: apatinib, gastric cancer (GC), conversion therapy, safety, efficacy

BACKGROUND: Zinc, an inorganic antibacterial material, has a suitable degradation rate and good antibacterial property. Adding alloying elements can improve the mechanical properties and biocompatibility of the material, which is the development direction of novel medical biodegradable metal materials. There is still lack a comparable research on the antibacterial properties among zinc-based materials. OBJECTIVE: To investigate the antibacterial properties of pure zine and zinc-based alloys in vivo. METHODS: Eighty Sprague-Dawley rats, SPF grade, were randomized into two groups (n=40/group) , and all rats were injected with Staphylococcus aureus or Escherichia coli solution to prepare infection models. Different materials (Zn, ZnAl, ZnSr, Zn3 Mg, Zn3 Ag, Zn3 Ca and Zn4 Cu; five rats for each material) were implanted into the medullary cavity of femur. The control group without any material was set. At 1, 4, 7 and 14 days after implantation, the changes of body temperature, white blood cell count, serum tumor necrosis factor α and serum zinc content in rats were detected. The secretions and tissues of the surgical site were collected to identify the bacterial species. RESULTS AND CONCLUSION: (1) The body temperature in all the rats was increased to different extents after bacterial infection, but the temperature of the rats implanted with zinc and zinc alloys was always lower than that in the control group at 7 and 14 days (P < 0.05) . The temperature in the Zn3 Ag group was significantly lower than that in the other groups at 7 and 14 days (P < 0.05) . (2) The white blood cell count and tumor necrosis factor α level in the zinc and zinc alloys groups were significantly lower than those in the control group at 7 and 14 days after implantation (P < 0.05) . The white blood cell count and tumor necrosis factor α level in the Zn3 Ag group were significantly lower than those in the other groups (P < 0.05) . (3) The serum zinc content in all groups has no significant difference (P> 0.05) . (4) The bacterial culture results showed S.aureus (+) in the Staphylococcus aureus infection group and E.coli (+) in the Escherichia coli infection group. (5) To conclude, degradable zinc-based alloys exert marked antibacterial effects, and Zn3 Ag alloys have the best antibacterial activity.

Objective To conduct the statistical analysis on the free carnitine and acylcarnitines levels in 0?6 years old children by detecting the contents of free carnitine and acylcarnitines in dry blood spot to provide the biological reference range for the diagnosis of fatty acid metabolic disorder and organic acidemia.Methods The levels of acylcarnitines of peripheral blood dry blood spot in 263 normal children were detected by using the isotopic dilution non-derived tandem mass spectrometry.All children were divided into male and female groups according to different genders and divided into the groups according to the age,1-28 d(gestational weeks ≥37 weeks),1-12 months old,13 months-3 years old and 4-6 years old.Results The detection results after normality test found that the levels of free carnitine and acylcarnitines in children showed a normality distribution.The free carnitine and various acylcarnitines levels had no statistical difference between male children and female children (t=0.5,P=0.619).The C4,C5,C6,C10,C12 and C18 had equal variance among various age groups(P>0.05) and could conducted the one way variance analysis;C0,C2,C3,C5,OH,C6,C8,C14,C16 and C18 had the variance heterogeneity among different age groups(P<0.05) and could conduct the rank-sum test(P<0.05).The C0,C2,C3,C5,OH,C6,C8,C10,C12,C14,C16 and C18 had statistical differences among different age groups,the reference value ranges were calculated according to different ages.The difference in C4 and C5 had no statistical significance and the reference value range could be calculated by the merged group.Conclusion It is a very important for the diagnosis and treatment of fatty acid metabolic disorder and organic acidemia to establish the reference value ranges of dry blood spot free carnitine and acylcarnitines in children according to different ages.

BACKGROUND:Dihydroartmisinin can promote apoptosis of glioma cels GL261, but its effect on glioma stem cels is stil unknown. OBJECTIVE:To investigate the preliminary mechanism that dihydroartemisinin inhibits migration and invasion of glioma stem cels. METHODS: Glioma stem cels were isolated from mouse malignant glioma cel lines GL261. Immunofluorescence analysis was conducted to identify the characteristics of glioma stem cels. Migration and invasion abilities of glioma stem cels were analyzed by Transwel assay. The mRNA expressions of Tol-like receptor 2, matrix metaloproteinase-2 and matrix metaloproteinase-9 were examined by real-time fluorescence quantitative PCR. RESULTS AND CONCLUSION:The characteristics of glioma stem cels were identified by CD133 and Nestin staining. The migration and invasion of glioma stem cels were attenuated by dihydroartemisinin dose-dependently. Moreover, the mRNA expression of Tol-like receptor 2, matrix metaloproteinase-2 and matrix metaloproteinase-9 was also decreased by dihydroartemisinin in a dose dependent manner. These results suggest that dihydroartemisinin inhibits the migration and invasion of glioma stem cels probably through attenuation of Tol-like receptor signaling pathway.

OBJECTIVETo evaluate the impact of primary site, NIH risk and imatinib treatment on the prognosis of patients with gastrointestinal stromal tumors(GIST).

METHODSClinicopathological data of 156 adult patients with GIST treated by imatinib in the Cancer Institute and Hospital of Tianjin Medical University from January 2006 to December 2010 were retrospectively analyzed. According to NIH risk classification, 30 patients were at moderate risk and 126 at high risk. Sixty-seven patients had advanced GIST. Prognosis of patients with different primary tumor site, different NIH risk and different treatment was compared respectively.

RESULTSImatinib therapy was well tolerated in all the patients. Eighty-nine cases received radical operation and adjuvant imatinib treatment. Among 67 advanced GIST cases, 26 received radical operation and adjuvant imatinib treatment, 27 received palliative operation and adjuvant imatinib treatment, and 14 received simple adjuvant imatinib treatment without operation. All the patients had routine follow-up, ranging from 9 to 56(median 27) months. The overall survival (OS) rate was 96% in 1-year, 86% in 2-year, and 71% in 3-year. The OS rate was 95% in 1-year, 77% in 2-year, and 65% in 3-year for patients at high risk, and all 100% in 1-, 2-, 3-year for patients at moderate risk, the differences was statistically significant (P=0.001). The OS rate was 97% in 1-year, 90% in 2-year, and 84% in 3-year for patients with gastric GIST, and 95% in 1-year, 69% in 2-year, and 52% in 3-year for patients with non-gastric GIST, the difference was significant(P=0.000). The OS rate was 98% in 1-year, 95% in 2-year, and 90% in 3-year for patients undergoing radical resection and adjuvant imatinib therapy. For 67 advanced GIST patients with imatinib therapy, none had complete remission, 41 had part remission, 15 had stable disease, indicating 56 advanced GIST cases(83.6%) obtaining clinical benefit. The OS rate was 91% in 1-year, 58% in 2-year, and 43% in 3-year.

CONCLUSIONSThe prognosis of high, and non-gastric and advanced GIST patients is poor. Radical resection combined with early imatinib treatment can improve the prognosis of GIST patients.

Antineoplastic Agents ; therapeutic use ; Benzamides ; therapeutic use ; Combined Modality Therapy ; Follow-Up Studies ; Gastrointestinal Neoplasms ; drug therapy ; pathology ; Gastrointestinal Stromal Tumors ; drug therapy ; Humans ; Imatinib Mesylate ; Piperazines ; therapeutic use ; Prognosis ; Pyrimidines ; therapeutic use ; Retrospective Studies ; Survival Rate

Objective To evaluate the impact of primary site, NIH risk and imatinib treatment on the prognosis of patients with gastrointestinal stromal tumors (GIST). Methods Clinicopathological data of 156 adult patients with GIST treated by imatinib in the Cancer Institute and Hospital of Tianjin Medical University from January 2006 to December 2010 were retrospectively analyzed. According to NIH risk classification, 30 patients were at moderate risk and 126 at high risk. Sixty-seven patients had advanced GIST. Prognosis of patients with different primary tumor site , different NIH risk and different treatment was compared respectively. Results Imatinib therapy was well tolerated in all the patients. Eighty-nine cases received radical operation and adjuvant imatinib treatment. Among 67 advanced GIST cases, 26 received radical operation and adjuvant imatinib treatment, 27 received palliative operation and adjuvant imatinib treatment, and 14 received simple adjuvant imatinib treatment without operation. All the patients had routine follow-up, ranging from 9 to 56 (median 27) months. The overall survival (OS) rate was 96% in 1-year, 86% in 2-year, and 71% in 3-year. The OS rate was 95% in 1-year, 77% in 2-year, and 65% in 3-year for patients at high risk, and all 100% in 1-, 2-, 3-year for patients at moderate risk, the differences was statistically significant (P=0.001). The OS rate was 97%in 1-year, 90% in 2-year, and 84% in 3-year for patients with gastric GIST, and 95% in 1-year, 69%in 2-year, and 52%in 3-year for patients with non-gastric GIST, the difference was significant(P=0.000). The OS rate was 98% in 1-year, 95% in 2-year, and 90% in 3-year for patients undergoing radical resection and adjuvant imatinib therapy. For 67 advanced GIST patients with imatinib therapy , none had complete remission, 41 had part remission, 15 had stable disease, indicating 56 advanced GIST cases (83.6%) obtaining clinical benefit. The OS rate was 91% in 1-year, 58% in 2-year, and 43% in 3-year. Conclusions The prognosis of high, and non-gastric and advanced GIST patients is poor. Radical resection combined with early imatinib treatment can improve the prognosis of GIST patients.

Objective To evaluate the impact of primary site, NIH risk and imatinib treatment on the prognosis of patients with gastrointestinal stromal tumors (GIST). Methods Clinicopathological data of 156 adult patients with GIST treated by imatinib in the Cancer Institute and Hospital of Tianjin Medical University from January 2006 to December 2010 were retrospectively analyzed. According to NIH risk classification, 30 patients were at moderate risk and 126 at high risk. Sixty-seven patients had advanced GIST. Prognosis of patients with different primary tumor site , different NIH risk and different treatment was compared respectively. Results Imatinib therapy was well tolerated in all the patients. Eighty-nine cases received radical operation and adjuvant imatinib treatment. Among 67 advanced GIST cases, 26 received radical operation and adjuvant imatinib treatment, 27 received palliative operation and adjuvant imatinib treatment, and 14 received simple adjuvant imatinib treatment without operation. All the patients had routine follow-up, ranging from 9 to 56 (median 27) months. The overall survival (OS) rate was 96% in 1-year, 86% in 2-year, and 71% in 3-year. The OS rate was 95% in 1-year, 77% in 2-year, and 65% in 3-year for patients at high risk, and all 100% in 1-, 2-, 3-year for patients at moderate risk, the differences was statistically significant (P=0.001). The OS rate was 97%in 1-year, 90% in 2-year, and 84% in 3-year for patients with gastric GIST, and 95% in 1-year, 69%in 2-year, and 52%in 3-year for patients with non-gastric GIST, the difference was significant(P=0.000). The OS rate was 98% in 1-year, 95% in 2-year, and 90% in 3-year for patients undergoing radical resection and adjuvant imatinib therapy. For 67 advanced GIST patients with imatinib therapy , none had complete remission, 41 had part remission, 15 had stable disease, indicating 56 advanced GIST cases (83.6%) obtaining clinical benefit. The OS rate was 91% in 1-year, 58% in 2-year, and 43% in 3-year. Conclusions The prognosis of high, and non-gastric and advanced GIST patients is poor. Radical resection combined with early imatinib treatment can improve the prognosis of GIST patients.