Humans ; Cardiovascular Diseases ; Risk Factors ; Myocardial Infarction/complications* ; Coronary Disease/etiology* ; Heart Disease Risk Factors

Objective:To evaluate the efficacy of oral pyrotinib in treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in the real world, and to explore its influencing factors.Methods:The clinical data of 148 patients with HER2-positive metastatic breast cancer treated with oral pyrrolitinib in Shanxi Cancer Hospital from September 2018 to December 2020 were retrospectively analyzed. The efficacy was evaluated according to the efficacy evaluation criteria for solid tumors, version 1.1, and the adverse effects were graded according to the National Cancer Institute common terminology criteria of adverse effects, version 4.0. The Kaplan-Meier method was used to draw progression-free survival (PFS) curves, the patients were stratified by different clinical characteristics, and log-rank test was used for univariate analysis of PFS; the multivariate analysis of PFS was performed using Cox proportional hazards model.Results:The objective response rate (ORR) of 148 patients was 71.6% (106/148), and the disease control rate (DCR) was 89.2% (132/148). The overall median PFS time was 11.0 months (95% CI 10.1-11.9 months), and the median PFS of 19 patients with brain metastases was 10.0 months (95% CI 7.4-12.6 months). The differences in PFS between patients stratified by disease-free interval (DFI), the number of metastatic site and Eastern Cooperative Oncology Group (ECOG) score were statistically significant (all P < 0.05), but the difference in PFS between patients with negative and positive hormone receptor was not statistically significant ( P > 0.05). Multivariate Cox regression analysis showed that DFI (>1 year vs. ≤1 year: HR = 5.254, 95% CI 0.728-37.933, P = 0.046) and ECOG score (≥2 points vs. 0-1 point: HR = 2.454, 95% CI 1.261-4.788, P = 0.008) were independent influencing factors of PFS. The most common ≥grade 3 adverse effects were diarrhea (31 cases, 20.9%) and hand-foot syndrome (38 cases, 25.8%). Conclusions:The pyrotinib has definite efficacy and good safety in the treatment of HER2-positive metastatic breast cancer in the real world, especially for patients with DFI > 1 year and ECOG score 0-1 point, the efficacy and safety are particularly good.

Objective:To recognize the overall situation of the core competency of medical professional postgraduate, analyze the advantages and disadvantages of the training process, and provide basis for better optimization and revision of training objectives and training plans.Methods:An anonymous online questionnaire was conducted among 264 postgraduates majoring in clinical medicine to recognize the cognition and self-evaluation of core competence, and analyze the differences in scores of different grades and types. SPSS 23.0 was used for independent-samples t test; and one-way analysis of variance to analyze categorical variables. Results:The doctoral degree students' core competency results were higher than those of master degree students, and those of the senior students were higher than junior students ( P<0.05). "System Improvement Ability" [master degree students (2.94±1.07), first-year students (2.82±0.97)], "Patient Management" [(first-year students (2.77±1.22)], "Academic Research" [first-year students (2.90±1.03)], and 4 other indicators were the weakness of students (all less than 3 scores). Conclusion:The students have a good sense of professional identity for doctors. The different depth of the clinical practice education is the possible cause which brings about the differences among students with different degrees. We should focus on strengthening the training for the "shortcomings" in the core competence of students.

Objective : To investigate the expression characteristics of mu opioid receptor ( MOR) in rat colon smooth muscle cells by cultured rat primary colonic smooth muscle cells . Methods : colonic smooth muscle cells were isolated , cultured and identified ; immunofluorescence double labeling method was used to observe the distribution characteristics of MOR , Endomorphin⁃2 (EM2) , and calmodulin (CaM) in colonic smooth muscle cells ; Western Blot method was used to detect the expression of MOR and EM2 in smooth muscle cells of the colon . After the intervention measures Acetylcholine (ACh) ( 1 × 10 - 3 mol/L) and EM2 (2 μmol/L) were applied , the changes of CaM protein expression were observed ; The calciumion imaging method was used to detect the changes of calciumi on concentration in smooth muscle cells. Results: The colonic smooth muscle cells were cultured and identified . The positive cells labeled with α ⁃smooth muscle actin ( α ⁃SMA) accounted for more than 95% of the total number of cells . Immunofluorescence double labeling showed that there were MOR and EM2 distributions in colonic smooth muscle cells , and all MOR and EM2 positive cells coexisted with α ⁃SMA . Western Blot results showed that there were MOR and EM2 expressions in colonic smooth muscle cells . CaM in the ACh group significantly increased at 10 minutes (P < 0. 05) , CaM in the EM2 group significantly decreased ( P < 0. 05) ; The calciumion imaging results showed that alone applied ACh , the calciumion concentration in smooth muscle cells significantly increased ( P <0. 05) ; Alone applied EM2 , the calciumion concentration in colonic smooth muscle cells was down⁃regulated (P <0. 05) ; Applied ACh and EM2 sequentially , EM2 significantly reduced the increase of the calciumion concentration in smooth muscle cells induced by ACh (P < 0. 05) . Conclusion MOR and EM2 are expressed in colonic smooth muscle cells , and EM2 may inhibit the expression of CaM and reduce the concentration of calcium ions through MOR .

Objective:To assess the safety and efficacy of riboflavin/ultraviolet-A-induced accelerated epithelium-off corneal collagen cross-linking (CXL) for teenagers with keratoconus.Methods:In this case series study, 25 eyes of 18 patients with primary keratoconus who underwent riboflavin/ultraviolet-A-induced accelerated epithelium-off CXL in Zhengzhou Second People's Hospital from January 2017 to February 2018 were included, and the average age of patients was (14.4±1.3) years.The uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), spherical equivalent (SE), maximum keratometry reading (K max), thinnest corneal thickness (TCT), posterior corneal elevation (PCE) and endothelial cell density (ECD) were measured before and after CXL.The patients were followed up for one year.The complications and adverse reactions were recorded.The study adhered to the Declaration of Helsinki and was approved by an Ethics Committee of Zhengzhou Second People's Hospital (No.KY2017002). Written informed consent was obtained from each patient and their guardian prior to the surgery. Results:The mean UCVA (LogMAR) was 0.96±0.35 at baseline, which was significantly improved to 0.84±0.33 at 1 year postoperatively ( t=-5.765, P<0.01). The mean BCVA (LogMAR) was 0.45±0.22 preoperatively, which was significantly improved to 0.34±0.26 at 1 year postoperatively ( t=-4.843, P<0.01). The mean SE was (8.66±5.11)D at baseline, which was significantly higher than (8.07±5.21)D at 1 year postoperatively ( t=-3.253, P=0.003). The K max was reduced from (58.58±9.07)D preoperatively to (56.25±9.98)D at 1 year postoperatively, with significant difference between the two time points ( t=-4.357, P<0.01). The K max was reduced more than 1 D in 17 eyes (68%), was stable in 6 eyes(24%), and was increased more than 1 D in 2 eyes (8%). The TCT was reduced from (485.0±32.5)μm at baseline to (475.3±35.5)μm at 1 year postoperatively, with significant difference between the two time points ( t=-4.266, P<0.01). The differences of PCE and ECD between preoperative and postoperative 1 year were not statistically significant ( t=1.023, P=0.316; t=-1.424, P=0.167). There was one eye suffering peripheral sterile corneal infiltrate 2 days postoperatively, and favorable prognosis was achieved after the topical steroids application.No complication was encountered in other subjects. Conclusions:Riboflavin/ultraviolet-A-induced accelerated epithelium-off CXL is safe and effective in teenagers with keratoconus during the 1-year follow-up.The long-term effects need further observation.

Objective To summarize the clinical features of patients with ovarian tumor associated anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis,and to explore the influence of operation patterns on the prognosis.Methods The clinical data of ovarian tumors with anti-NMDAR encephalitis in the Third Affiliated Hospital of Sun Yat-sen University from January 2009 to December 2018 were collected,and the clinical characteristics,treatment and prognosis were analyzed.Results A total of 110 patients with ovarian tumors and anti-NMDAR encephalitis were collected.All patients were positive for anti-NMDAR antibodies in serum and/or cerebrospinal fluid.The age of onset ranged from 10 to 35 years (24.6 ±5.7).About 60.9％ patients'initial symptom was psychosis.The main clinical features were psychosis (97.3％),seizures (83.6％),conscious disturbance (72.7％),autonomic dysfunction (64.5％),dyskinesia (64.5％),central hypoventilation (54.5％) and impaired memory (31.8％).Most patients'symptoms were relieved after surgery and immunotherapy.Postoperative pathological results revealed that ovarian teratoma accounted for 97.8％ of the ovarian tumor.The prognosis of patients with surgery was better than the patients without surgery,with statistically significant difference (P ＜ 0.05).The prognosis of patients with adnexectomy was better than the patients with ovarian tumor excision,with statistically significant difference (P ＜ 0.05).Conclusions Anti-NMDAR encephalitis,with psycho-neurological symptoms as dominant manifestation,is usually associated with ovarian tumor.For young female patients with psychosis,clinicians should be alert to the possibility of anti-NMDAR encephalitis and screen for tumor.Patients with adnexectomy and immunotherapy can get a better prognosis.

Objective To investigate the diagnostic value of fine needle aspiration biopsy combined with BRAFV600E gene mutation detection in elderly patients with thyroid nodules.Methods A total of 168 elderly patients with thyroid nodules suspicious for malignancy on ultrasound from January 2017 to December 2017 at our hospital were enrolled in this study.Using color Doppler ultrasound,185 thyroid nodules were found.Fine needle aspiration cytology(FNAC)and BRAFV600E gene mutation detection were performed before surgery and the findings were compared with postoperative pathological results.The diagnostic value of single and combined detection of FNAC and BRAFV600E gene mutation was evaluated.Results Among 185 thyroid nodules,there were 146 malignant lesions including 137 papillary carcinomas and 9 follicular carcinomas,and 39 benign lesions including 31 cases of nodular goiter,5 cases of Hashimoto's thyroiditis and 3 cases of adenoma.The sensitivity,specificity,accuracy,positive predictive value and negative predictive value of FNAC were 79.5％,59.0％,75.1％,75.2％,and 45.6％,respectively.The sensitivity,specificity,accuracy,positive predictive value and negative predictive value of BRAFV600E gene mutation detection were 78.1％,51.3 ％,72.4 ％,84.4 ％ and 51.2 ％,respectively.The sensitivity,specificity,accuracy,positive predictive value and negative predictive value of the combined detection were 93.4％,77.5％,86.2％,90.8％ and 53.4％,respectively.The sensitivity,specificity,accuracy,positive predictive value and negative predictive value of the combined detection were higher than those of either method used alone (all P＜0.05).Conclusions For some thyroid nodules that cannot be unequivocally diagnosed as benign or malignant by FNAC,the combined detection of FNAC and BRAFV600E gene mutation can significantly improve the sensitivity,specificity and accuracy of malignancy detection,differentiate between benign and malignant nodules,and help formulate operation plans and subsequent treatment.

OBJECTIVE： To prepare Adriamycin hydrochloride （DOX） magnetic thermosensitive liposome （MTSL）， investigate its physicochemical properties， magnetic effect and photothermal effect， so as to provide reference for tumor chemo- therapy and photodynamic/photothermal therapy. METHODS： Using DOX as model drug， TiO2@Fe3O4 as photosensitizers and magnetic materials， DOX-TiO2@Fe3O4-MTSL was prepared with membrane dispersion method. The morphology and dispersibility were observed； particle size and Zeta potential were detected； encapsulation efficiency of the liposome were determined by centrifugal ultrafiltration and HPLC. Its paramagnetism property was also detected by magnetometer. Compared with DOX solution， in vitro release behavior of the liposome was investigated by dialysis method， and the release curves at different temperatures （at 37， 43 ℃） were compared. The photothermal conversion effect of the liposome and the production of reactive oxygen species （ROS） in human breast cancer MCF-7 cells were investigated by near infrared laser irradiation at 808 nm. RESULTS： Prepared DOX-TiO2@Fe3O4-MTSL was brown-black with good water dispersion， and was spherical in shape and uniform in size under electron microscopy. Average particle size was 250.6 nm； polydispersity index was 0.107； Zeta potential was （－7.76±3.41）mV； encapsulation efficiency was （92.3±3.2）％. Under the external magnetic field， the liposome could move in a directional direction and had obvious paramagnetism. Compared with DOX solution， the liposomes released slowly and showed obvious sustained- release characteristics. Compared with at 37 ℃， the drug release of liposome speeded up significantly at 43 ℃.With the increase of laser （808 nm） irradiation time， the temperature of the liposome kept rising， which had obvious photothermal conversion effect and could induce the increase of ROS in MCF-7 cells. CONCLUSIONS： DOX-TiO2@Fe3O4-MTSL is prepared succe- ssfully， which has uniform appearance， good physical and chemical properties. It has obvious paramagnetism sustained release effect and photothermal conversion efficiency， and can promote ROS production in MCF-7 cells under near infrared laser irradiation at 808 nm.

Objective To evaluate effect of dexmedetomidine on mitochondrion-dependent apoptosis during hypoxia-reoxygenation (H/R) injury to hippocampal neurons of rats.Methods The primarily cultured hippocampal neurons of Sprague-Dawley rats were divided into 4 groups (n =40 each) using a random number table method:control group (C group),vehicle group (V group),H/R group and dexmedetomidine group (D group).Hippocampal neurons were subjected to oxygen-glucose deprivation followed by restoration of oxygen supply to establish the model of H/R injury.Dexmedetomidine 1 μmol/L was added at 6 h of reoxygenation in D group.The viability of neurons was measured by methyl thiazolyl tetrazolium assay at 20 h of reoxygenation.The ultrastructure of mitochondria was observed by transmission electron microscopy.The expression of cytochrome c (Cyt c),caspase-3,Fis1 and Drp1 was detected by Western blot.The neuronal apoptosis was detected by flow cytometry,and apoptosis rate was calculated.Results Compared with C group,no significant change was found in the viability of neurons in group V (P＞0.05),and the viability of neurons was significantly decreased,the apoptosis rate was increased,the expression of Cyt c,caspase-3,Fis1 and Drp1 was up-regulated (P＜0.05),and the damage to mitochondrial ultrastructure was accentuated in H/R and D groups.Compared with H/R group,the viability of neurons was significantly increased,the apoptosis rate was decreased,the expression of Cyt c,caspase-3,Fis1 and Drp1 was down-regulated (P＜0.05),and the damage to mitochondrial ultrastructure was significantly attenuated in D group.Conclusion The nechanism by which dexmedetomidine reduces the H/R injury to hippocampal neurons is related to inhibiting mitochondrion-dependent apoptosis in rats.

Objective To investigate the relationship between serum 25-OH vitamin D3 (25-OHD3)levels and carpal tunnel syndrome(CTS)in type 2 diabetes.Methods Data from 102 patients with type 2 diabetes were collected,and patients were divided into a CTS group(n=29)and a non-CTS group(n=73)according to clinical symptoms,signs,and electrophysiological testing.Fasting venous blood was collected to assay serum 25-OHD3 levels that were compared between the two groups.The correlation between 25-OHD3 and clinical parameters for type 2 diabetes was analyzed.Results The incidence of vitamin D3 deficiency was 65.5％ (n=19)in the CTS group and 46.6％(n=34)in the non CTS group,and the difference was statistically significant(x2 =16.85,P＜0.01).Levels of 25-OHD3 were lower in the CTS group(14.13±4.91) μg/L than in the non-CTS group(17.08±3.35)μg/L(t =4.067,P ＜ 0.01).Levels of 25 OHD3 were negatively correlated with those of glycosylated hemoglobin(HbA1c)(r =-0.176,P =0.041)and the duration of diabetes(r=-0.29,P=0.01) Conclusions Low 25-OHD3 is a risk factor for carpal tunnel syndrome in type 2 diabetes and is negatively associated with the duration of diabetes and HbA1c in patients with type 2 diabetes.