Synergistic effect of β-thujaplicin and tigecycline against tet(X4)-positive Escherichia coli in vitro / 生物工程学报

The widespread of tigecycline resistance gene tet(X4) has a serious impact on the clinical efficacy of tigecycline. The development of effective antibiotic adjuvants to combat the looming tigecycline resistance is needed. The synergistic activity between the natural compound β-thujaplicin and tigecycline in vitro was determined by the checkerboard broth microdilution assay and time-dependent killing curve. The mechanism underlining the synergistic effect between β-thujaplicin and tigecycline against tet(X4)-positive Escherichia coli was investigated by determining cell membrane permeability, bacterial intracellular reactive oxygen species (ROS) content, iron content, and tigecycline content. β-thujaplicin exhibited potentiation effect on tigecycline against tet(X4)-positive E. coli in vitro, and presented no significant hemolysis and cytotoxicity within the range of antibacterial concentrations. Mechanistic studies demonstrated that β-thujaplicin significantly increased the permeability of bacterial cell membranes, chelated bacterial intracellular iron, disrupted the iron homeostasis and significantly increased intracellular ROS level. The synergistic effect of β-thujaplicin and tigecycline was identified to be related to interfere with bacterial iron metabolism and facilitate bacterial cell membrane permeability. Our studies provided theoretical and practical data for the application of combined β-thujaplicin with tigecycline in the treatment of tet(X4)-positive E. coli infection.

Differences in clinicopathological features, gene mutations, and prognosis between primary gastric and intestinal gastrointestinal stromal tumors in 1061 patients / 中华胃肠外科杂志

Objective: To analyze the clinicopathological features and gene mutations of primary gastrointestinal stromal tumors (GISTs) of the stomach and intestine and the prognosis of intermediate- and high-risk GISTs. Methods: This was a retrospective cohort study. Data of patients with GISTs admitted to Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2019 were collected retrospectively. Patients with primary gastric or intestinal disease who had undergone endoscopic or surgical resection of the primary lesion and were confirmed pathologically as GIST were included. Patients treated with targeted therapy preoperatively were excluded. The above criteria were met by 1061 patients with primary GISTs, 794 of whom had gastric GISTs and 267 intestinal GISTs. Genetic testing had been performed in 360 of these patients since implementation of Sanger sequencing in our hospital in October 2014. Gene mutations in KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 were detected by Sanger sequencing. The factors investigated in this study included: (1) clinicopathological data, such as sex, age, primary tumor location, maximum tumor diameter, histological type, mitotic index (/5 mm2), and risk classification; (2) gene mutation; (3) follow-up, survival, and postoperative treatment; and (4) prognostic factors of progression-free survival (PFS) and overall survival (OS) for intermediate- and high-risk GIST. Results: (1) Clinicopathological features: The median ages of patients with primary gastric and intestinal GIST were 61 (8-85) years and 60 (26-80) years, respectively; The median maximum tumor diameters were 4.0 (0.3-32.0) cm and 6.0 (0.3-35.0) cm, respectively; The median mitotic indexes were 3 (0-113)/5 mm² and 3 (0-50)/5 mm², respectively; The median Ki-67 proliferation indexes were 5% (1%-80%) and 5% (1%-50%), respectively. The rates of positivity for CD117, DOG-1, and CD34 were 99.7% (792/794), 99.9% (731/732), 95.6% (753/788), and 100.0% (267/267), 100.0% (238/238), 61.5% (163/265), respectively. There were higher proportions of male patients (χ²=6.390, P=0.011), tumors of maximum diameter > 5.0 cm (χ²=33.593, P<0.001), high-risk (χ²=94.957, P<0.001), and CD34-negativity (χ²=203.138, P<0.001) among patients with intestinal GISTs than among those with gastric GISTs. (2) Gene mutations: Gene mutations were investigated in 286/360 patients (79.4%) with primary gastric GISTs and 74/360 (20.6%) with primary intestinal GISTs. Among the 286 patients with gastric primary GISTs, 79.4% (227/286), 8.4% (24/286), and 12.2% (35/286), had KIT mutations, PDGFRA mutations, and wild-type, respectively. Among the 74 patients with primary intestinal GISTs, 85.1% (63/74) had KIT mutations and 14.9% (11/74) were wild-type. The PDGFRA mutation rate was lower in patients with intestinal GISTs than in those with gastric GISTs[ 0% vs. 8.4%(24/286), χ²=6.770, P=0.034], whereas KIT exon 9 mutations occurred more often in those with intestinal GISTs [22.2% (14/63) vs. 1.8% (4/227), P<0.001]. There were no significant differences between gastric and intestinal GISTs in the rates of KIT exon 11 mutation type and KIT exon 11 deletion mutation type (both P>0.05). (3) Follow-up, survival, and postoperative treatment: After excluding 228 patients with synchronous and metachronous other malignant tumors, the remaining 833 patients were followed up for 6-124 (median 53) months with a follow-up rate of 88.6% (738/833). None of the patients with very low or low-risk gastric (n=239) or intestinal GISTs (n=56) had received targeted therapy postoperatively. Among 179 patients with moderate-risk GISTs, postoperative targeted therapy had been administered to 88/155 with gastric and 11/24 with intestinal GISTs. Among 264 patients with high-risk GISTs, postoperative targeted therapy had been administered to 106/153 with gastric and 62/111 with intestinal GISTs. The 3-, 5-, and 10-year PFS of patients with gastric or intestinal GISTs were 96.5%, 93.8%, and 87.6% and 85.7%, 80.1% and 63.3%, respectively (P<0.001). The 3-, 5-, and 10-year OS were 99.2%, 98.8%, 97.5% and 94.8%, 92.1%, 85.0%, respectively (P<0.001). (4) Analysis of predictors of intermediate- and high-risk GISTs: The 5-year PFS of patients with gastric and intestinal GISTs were 89.5% and 73.2%, respectively (P<0.001); The 5-year OS were 97.9% and 89.3%, respectively (P<0.001). Multivariate analysis showed that high risk (HR=2.918, 95%CI: 1.076-7.911, P=0.035) and Ki-67 proliferation index > 5% (HR=2.778, 95%CI: 1.389-5.558, P=0.004) were independent risk factors for PFS in patients with intermediate- and high-risk GISTs (both P<0.05). Intestinal GISTs (HR=3.485, 95%CI: 1.407-8.634, P=0.007) and high risk (HR=3.753,95%CI:1.079-13.056, P=0.038) were independent risk factors for OS in patients with intermediate- and high-risk GISTs (both P<0.05). Postoperative targeted therapy was independent protective factor for PFS and OS (HR=0.103, 95%CI: 0.049-0.213, P<0.001; HR=0.210, 95%CI:0.078-0.564,P=0.002). Conclusions: Primary intestinal GIST behaves more aggressively than gastric GISTs and more frequently progress after surgery. Moreover, CD34 negativity and KIT exon 9 mutations occur more frequently in patients with intestinal GISTs than in those with gastric GISTs.

Evaluation of metoprolol standard dosing pathway in Chinese patients with acute coronary syndrome: a prospective multicenter single-arm interventional study / 老年心脏病学杂志（英文版）

OBJECTIVE@#To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS).@*METHODS@#In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4.@*RESULTS@#Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group.@*CONCLUSIONS@#In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

Analysis of clinicopathological features, gene mutation characteristics and prognosis of 228 cases of primary gastrointestinal stromal tumor of small intestine / 中华消化杂志

Objective:To analyze the clinicopathological features, gene mutation characteristics, and prognostic related factors of patients with primary gastrointestinal stromal tumor (GIST) of small intestine.Methods:From January 1, 2011 to December 30, 2019, surgical resected and pathological diagnosed small intestinal GIST without preoperative adjuvant therapy, at Tianjin Medical University Cancer Institute & Hospital were retrospectively collected. The mutational status of KIT exons 9, 11, 13, and 17 and platelet-derived growth factor receptor alpha ( PDGFRA) exons 12 and 18 were detected by polymerase chain reaction and Sanger direct sequencing. Clinicopathological features and gene mutation characteristics were analyzed. Pearson chi-square test and Bonferroni continuous correction test were used to compare the categorical variables among groups. Kaplan-Meier method and log-rank test were used for univariate survival analysis. The multivariate Cox proportional hazards regression model was used for multivariate survival analysis. Results:The proportions of patients with maximum tumor diameter> 10.0 cm and high-risk GIST located in the jejunum and ileum were higher than those of patients with primary GIST located in the duodenum (18.7%, 28/150 vs. 6.4%, 5/78; 56.7%, 85/150 vs. 43.6%, 34/78), and the differences were statistically significant ( χ2=14.67 and 12.46, P=0.002 and 0.006). The results of gene detection of 58 cases of small intestinal GIST indicated that the percentage of KIT gene mutant and wild type accounted for 84.5% (49/58) and 15.5% (9/58), among which 34 cases (69.4%), 12 cases (24.5%), 2 cases (4.1%) and 1 case (2.0%) were KIT gene exons 11, 9, 13 and 17 mutations, respectively, and none of the case with PDGFRA mutation. The 3-, 5-, and 10-year progression-free survival rates of the patients with small intestinal GIST were 88.1%, 85.0%, and 68.3%, respectively, and the 3-, 5-, and 10-year overall survival rates were 96.6%, 94.5%, and 86.1%, respectively. The results of univariate survival analysis showed that the progression-free survival rate and overall survival rate of patients with very low-risk and low-risk GIST were higher than those of patients with intermediate-risk and high-risk GIST (100.0%, 49/49 vs. 72.3%, 81/112; 100.0%, 49/49 vs. 89.3%, 100/112, respectively), and the differences were statistically significant ( χ2=14.07 and 4.92, P<0.001、=0.027). The results of univariate survival analysis of patients with intermediate-risk and high-risk GIST showed that the epithelioid cell type, mitotic index >5/5 mm 2, Ki-67 proliferation index >5%, and without postoperative adjuvant therapy were all related with progression-free survival time, and the differences were statistically significant ( χ2=8.39, 5.53, 13.73 and 15.44, P=0.004、0.019、<0.001、<0.001). Without postoperative adjuvant therapy was related with poor overall survival time ( χ2=7.06, P=0.008). The results of univariate analysis in patients with intermediate-risk and high-risk GIST and without postoperative adjuvant therapy showed that the epithelioid cell type, high-risk, mitotic index >5/5 mm 2 and Ki-67 proliferation index >10% were all related with progression-free survival time, and the differences were statistically significant ( χ2=10.08, 6.51, 10.37 and 15.72, P=0.001、0.011、0.001、<0.001). The results of multivariate analysis indicated that Ki-67 proliferation index >5% ( HR=5.018, 95% confidence interval(95% CI) 1.745 to 14.430, P=0.003) and without postoperative adjuvant treatment ( HR=0.145, 95% CI 0.051 to 0.414, P<0.001) were independent risk factors of postoperative tumor progression in patients with small intestinal intermediate-risk and high-risk GIST. Ki-67 proliferation index>10% ( HR=8.381, 95% CI 1.364 to 51.487, P=0.022) was an independent risk factor of postoperative tumor progression in patients with small intestinal intermediate-risk and high-risk GIST and without postoperative adjuvant treatment. Conclusions:The most common mutation in small intestinal primary GIST is KIT mutation, followed by wild type, no case of PDGFRA gene mutation has been found. High Ki-67 proliferation index can predict poor prognosis of patients with moderate-risk and high-risk small intestinal primary GIST. Postoperative adjuvant therapy can significantly improve the prognosis of patients with small intestinal intermediate-risk and high-risk primary GIST.

Serum Ferritin and the Risk of Metabolic Syndrome: A Systematic Review and Dose-Response Meta-Analysis of Cross-sectional Studies / 生物医学与环境科学（英文）

Objective@#This study aims to assess the dose-response relationship between serum ferritin (SF) and metabolic syndrome (MetS) in the two sexes.@*Methods@#We searched for articles on PubMed, the Cochrane Library, EMBASE, and the Web of Science databases that were published from 1950 to 2020. The summary odds ratio ( @*Results@#This study included 14 studies and 74,710 samples. The results of the classical meta-analysis showed that SF was positively associated with MetS ( @*Conclusions@#Our study shows that SF is significantly and positively associated with MetS, and the risk in the male population is higher than that in the female population. This finding also supports the recommendation of using SF as an early warning marker of MetS.

Association of status of mismatch repair protein expression and EB virus infection with clinicopathological parameters in 886 gastric adenocarcinoma patients / 中华胃肠外科杂志

Objective: To analyze the expression of mismatch repair (MMR) protein and the EB virus infection in gastric adenocarcinoma, and to examine the association of MMR expression and EB virus infection with clinicopathological parameters. Methods: A case-control study was performed. Clinicopathological data of patients who was pathologically diagnosed as gastric adenocarcinoma, received radical gastrectomy and had complete clinicopathological data from August 2017 to April 2020 in Tianjin Medical University Cancer Institute and Hospital were retrospectively collected and analyzed. The immunohistochemistry (IHC) of MMR proteins and in situ hybridization (ISH) of Epstein-Barr virus encoded RNA (EBER) were reviewed. The associations of MMR and EBER results with clinicopathological parameters were analyzed. The main observations of the study were MMR and EBER expression, and association of MMR and EBER results with clinicopathological parameters. Results: Eight hundred and eighty-six patients were enrolled, including 98 patients who received preoperative neoadjuvant chemoradiotherapy. Of 886 patients, 613 (69.2%) were males and the median age was 60 (22-83) years; 831 (93.8%) were mismatch repair proficiency (pMMR), and 55 (6.2%) were mismatch repair deficiency (dMMR). In dMMR group, 47 cases (85.5%) had the deficiency of both MLH1 and PMS2, 1 case (1.8%) had the deficiency of both MSH2 and MSH6, 4 cases (7.3%) had the deficiency only in PMS2, 2 cases (3.6%) had the deficiency only in MSH6, and 1 case (1.8%) had the deficiency only in MSH2. The deficiency rates of PMS2, MLH1, MSH6 and MSH2 were 5.8% (51/886), 5.3% (47/886), 0.3% (3/886) and 0.2% (2/886), respectively. Among the 871 cases with EBER results, 4.9% (43/871) were positive EBER. Univariate analysis showed that dMMR was more frequently detected in female patients (χ(2)=10.962, P=0.001), cancer locating in the antrum (χ(2)=9.336,P=0.020), Lauren intestinal type (χ(2)=9.718, P=0.018), stage T3 (χ(2)=25.866, P<0.001) and TNM stage II (χ(2)=15.470, P=0.002). The ratio of dMMR was not significantly associated with age, tumor differentiation, histological type, lymph node metastasis, distant metastasis or Her-2 immunohistochemical score (all P>0.05). Compared with negative EBER, positive EBER was more frequent in male patients (χ(2)=9.701, P=0.002), cancer locating in gastric fundus and corpus (χ(2)=17.964, P<0.001), gastric cancer with lymphoid stroma (χ(2)=744.073, P<0.001) and poorly differentiated cancer (χ(2)=13.739, P=0.010). Positive EBER was not significantly associated with age, depth of invasion, lymph node metastasis, distant metastasis, TNM stage or Her-2 immunohistochemical score (all P>0.05). In addition, all dMMR cases were EBER negative, and all cases of positive EBER were pMMR. Conclusions: The positive EB virus status is mutually exclusive with dMMR, indicating that different molecular subtypes of gastric adenocarcinoma are involved in different molecular pathways in tumorigenesis and progression. The overlapping of dMMR or positive EBER status and positive Her-2 expression is found in some cases of gastric adenocarcinoma. Patients with gastric adenocarcinoma after radical surgery should be tested for MMR status if they are female, the tumor locates in gastric antrum, the TNM staging is stage II or T3, or if the Lauren classification is intestinal type. And if patients are male, the tumor locates in the gastric fundus and corpus, the cancer is lymphoid stroma, or poor differentiated, the expression of EBER should be detected. Results of our study may provide evidence for further decision-making of clinical treatment.

Effect of electroacupuncture on expression of GABA receptor mRNA in different brain regions in rats with chronic inflammatory pain / 中国针灸

OBJECTIVE@#To observe the expression of GABA receptor mRNA in different brain regions of the central nervous system in chronic inflammatory pain rats and the intervention effect of electroacupuncture (EA).@*METHODS@#A total of 48 SPF male SD rats were randomly divided into a blank control group, a model control group, an EA group and a sham EA group, 12 rats in each group. The model of chronic inflammatory pain was established by injecting Freund's complete adjuvant into the foot. The EA group was treated with EA 28 days after the model establishment. The "Housanli" (ST 36) and "Kunlun" (BL 60) were selected and treated with dilatational wave, 2 Hz/100 Hz in frequency, 0.5-1.5 mA for 30 min; EA was given only once. In the sham EA group, the same acupoints were selected but the needles were only inserted into subcutaneous area; EA was connected for 30 min without electrical stimulation. The behavior changes of mechanical pain threshold and thermal pain threshold before model establishment, 1 day, 3 days, 7 days, 14 days, 21 days and 28 days after the model establishment as well as emotional behavior 29 days after the model establishment were observed; the relative expressions of GABA receptor mRNA in anterior cingulate cortex, amygdala and hypothalamus were observed.@*RESULTS@#Compared with the blank control group, the change rates of mechanical pain threshold and thermal pain threshold in the model control group were decreased significantly 1 day, 3 days, 7 days, 14 days, 21 days, 28 days after model establishment (0.05). Compared with the blank control group, the expression of GABA receptor mRNA in the amygdala was decreased significantly in the model control group (<0.01); compared with the model control group and the sham EA group, the expression of GABA receptor mRNA in amygdala was increased after intervention in the EA group (<0.01).@*CONCLUSION@#Single treatment of EA could significantly increase the mechanical pain threshold and thermal pain threshold, improve abnormal emotional behavior in rats with chronic inflammatory pain, which may be related to the increasing of expression of GABA receptor mRNA in the amygdala.

Effect of transcutaneous electrical acupoint stimulation on catheter related bladder discomfort after ureteroscopic lithotripsy / 中国针灸

OBJECTIVE@#To verify the efficacy of transcutaneous electrical acupoint stimulation (TEAS) on catheter related bladder discomfort after ureteroscopic lithotripsy.@*METHODS@#Sixty male patients with selective ureteroscopic lithotripsy under general anesthesia were randomly divided into a TEAS group (30 cases, one case dropped off) and a sham TEAS group (30 cases, 2 cases dropped off). Before anesthesia induction, the patients in the TEAS group were treated with TEAS at Guanyuan (CV 4), Zhongji (CV 3), Zusanli (ST 36) and Sanyinjiao (SP 6) for 30 min, with disperse-dense wave, frequency of 2 Hz/ 15 Hz and current intensity of 6 to 10 mA. The patients in the sham TEAS group were treated with the same TEAS device at the same acupoints, but no electrical stimulation was given. After 30 min, anesthesia induction started. The total dosages of propofol and remifentanil in the two groups were recorded, and the time of operation and anesthesia, the time of wake-up and the time of stay in postanesthesia care unit (PACU) were recorded. The postoperative recovery was evaluated 5 min (T) after wake-up, 1 h (T), 2 h (T) and 6 h (T) after the operation, including the severity of urinary tract irritation and visual analogue scale (VAS) score. The occurrence of adverse reactions was observed, such as nausea and vomiting, dizziness and headache.@*RESULTS@#The dosage of remifentanil in the TEAS group was significantly lower than that in the sham TEAS group (0.05). Compared with the sham TEAS group, the incidence of more-than-moderate urinary tract irritation symptoms in the TEAS group was reduced (<0.05), and the VAS scores 1 and 2 h after operation were reduced (<0.05).@*CONCLUSION@#The 30-min TEAS at Guanyuan (CV 4), Zhongji (CV 3), Zusanli (ST 36) and Sanyinjiao (SP 6) before anesthesia induction could significantly control the severity of postoperative urinary tract irritation in patients with ureteroscopic lithotripsy, reduce the dosage of anesthetic drugs and relieve postoperative pain.

Efficacy and safety of PEG-rhG-CSF therapy in the primary and secondary prevention of chemotherapy-induced neutropenia / 中国肿瘤临床

Objective: To evaluate the efficacy and safety of PEG-rhG-CSF therapy in the primary and secondary prevention of chemo-therapy-induced neutropenia . Methods: This single-center, one-arm, and open-label clinical study involved 217 patients with non-my-eloid malignant tumors. These patients included 18 gynecologic oncology (3 endometrial and 15 ovarian cancer), 50 breast cancer, 30 bone tumor, and 119 lymphoma patients who underwent a total of 774 cycles of chemotherapy, comprising 146 primary and 71 sec-ondary prevention patients. The patients ≥45 kg and those <45 kg received a single subcutaneous injection of 6 mg and 3 mg PEG-rhG-CSF, respectively, 24-48 h after the chemotherapy was completed. All patients received only one dose of PEG-rhG-CSF admin-istration per chemotherapy cycle. Results: The overall incidence of febrile neutropenia (FN) was found to be 5.7%, with rates of 4.9% and 7.2% in the primary and secondary prevention groups, respectively. Univariate and multivariate Logistic regression analyses re-vealed that the longer PEG-rhG-CSF was sustained in the treatment cycle, the lower the incidence of FN was. The incidence of FN was significantly lower in the second cycle of the treatment than in the first in both the primary and secondary prevention groups (cycle 1 vs. cycle 2: 11.6% vs. 4.4%, respectively, P=0.039, in the primary group; 16.9% vs. 5.6%, respectively, P=0.034, in the secondary group). The overall incidence of gradeⅣneutropenia was 10.3% (80/774), with rates of 6.7% (34/510) and 17.4% (46/264) in the primary and secondary prevention groups, respectively (P<0.001). The incidence of gradeⅣneutropenia was significantly lower in the second cy-cle of the treatment than in the first (cycle 1 vs. cycle 2: 17.1% vs. 5.3%, respectively, P=0.004, in the primary group; 46.5% vs. 11.3%, respectively, P<0.001, in the secondary group). The treatment-induced toxicity mainly involved bone pain, with 3.7% (8/217) and 1.8% (4/217) incidence rates for grade 1-2 and 3-4 bone pain, respectively. Conclusions: PEG-rhG-CSF administration can effectively reduce the incidence of FN (5.7%) when prophylactically applied to patients with non-myeloid malignant tumors. Primary prevention can sig- nificantly reduce the risk of grade IV neutropenia in all chemotherapy cycles relative to the secondary prevention.

Clinicopathological characteristics and prognostic factors of gastric neuroendocrine neoplasms: an analysis of 117 cases / 中国肿瘤临床

Objective: To explore the clinicopathological characteristics and prognostic factors of gastric neuroendocrine neoplasm (NEN). Methods: Clinicopathological parameters and follow-up data collected from 117 patients with gastric NEN at Tianjin Medical University Cancer Institute and Hospital from March 2011 to December 2017 were reviewed, classified, and graded according to World Health Or-ganization (WHO) 2010 classification. Clinicopathological characteristics of different types and grades of gastric NEN were compared and survival analysis was performed. Results: Among the 117 cases confirmed as gastric NEN, this entire cohort comprised 13 cases (11.1%) of neuroendocrine tumor (NET) G1, 6 cases (5.1%) of NET G2, 57 cases (48.7%) of neuroendocrine carcinoma (NEC), and 41 cases (35.1%) of mixed adenoneuroendocrine carcinoma (MANEC). Gastric NET G1 and G2 typically consisted of multiple small tumors with shallow invasion and infrequent lymphatic and distant metastases at early stages at the time of diagnosis. The treatment of patients with gastric NET included endoscopic submucosal dissection and radical surgical resection. Precursor neuroendocrine lesions were detected in most cases. The patients with gastric NET G1 and G2 had a good prognosis. Gastric NEC and MANEC mostly consisted of single large tumors with deep infiltration, and common lymphatic and distant metastases at advanced stages when the diagnoses were confirmed. All the patients with gastric NEC and MANEC underwent surgical resection, and most received adjuvant therapy. Histopathological changes of gastric NEC were characterized by large cells and poorly differentiated tumors, while gastric MANEC had various forms of neuroendocrine and adenocarcinoma components. The prognosis of patients with gastric NEC and MANEC was poor for both; however, the predictors of progression-free survival and overall survival were different between gastric NEC and MANEC. Conclusions: Gastric NEN are a group of heterogeneous tumors with different clinicopathological features and prognosis. More multicenter studies with large sample sizes are still needed to improve the classification of gastric NEN and explore the prognostic factors.

Relationships of polymorphism of APOE gene and cognitive impairment in patients with CNS demyelinat-ing diseases / 中国神经精神疾病杂志

Objective To investigate the association between the level of polymorphism of APOE gene and cognitive impairment in patients with CNS demyelinating diseases. Methods 56 patients with central nervous system demyelinating disease were applied APOE genotyping,MoCA and expanded disability status (EDSS) scale score. Patients with MOCA scores <26 were divided into cognitive impairment group, and those with MOCA scores ≥26 were divided into normal cognitive preserved group. Results The probability of cognitive dysfunction in patients with central nervous system demyelinating diseases was 53.57%. There was no significant difference in age, gender, and disease duration between the CI group and the CP group(P>0.05), the difference in age and education among groups is statistically significant (P<0.05). There was no statistical significance in the difference in age, sex, education years and EDSS score between APOEε4 gene positive group and APOEε4 gene negative group (P<0.05). The difference of visual space and attention between different cognitive domains is statistically significant(P<0.05). Years of schooling is a risk factor for cognitive dysfunction in patients with central nervous system demyelinating disease(P<0.01). Conclusion The central nervous system demyelinating disease is impaired cognitive function. Patients with APOEε4 gene positive are more severely impaired in visual space and attention than patients with negative APOEε4 gene.Years of education are the risk factors of cognitive dysfunction in patients with central nervous system demyelinating disease. The course of disease and disabled function may not be significant related to cognitive impairment.

Colorectal cancer preventive effect of combined administration of phenolic acids and supercritical extracts from Angelica sinensis / 中国中药杂志

This study aimed to investigate the colorectal cancer preventive effect of the combined administration of phenolic acids and supercritical extracts from Angelica sinensis. The AOM/DSS model in mice was adopted. Phenolic acids were administrated orally in the initial stage of the model at a dose of 1 g·kg⁻¹ BW, which was combined withtherectal administration with three doses of supercritical extracts (15, 30, 60 g·kg⁻¹ BW). PCNA, 8-oxoguaine, γ-H2AX, iNOS and COX-2 were tested by immunohistochemistry and Western blot assays. The results showed that the combined administration of phenolic acids and supercritical extracts from A. sinensis suppressed the tumor growth and cell proliferation, and DNA damages and inflammatory responses were reduced in a dose-dependent manner. These results indicate that the combined administration of phenolic acids and supercritical extracts from A. sinensis have a certain effect in preventing carcinogenesis.

Role of Jagged1-Hey1 Signal in Angiotensin II-induced Impairment of Myocardial Angiogenesis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Angiotensin II (Ang II) is a major contributor to the development of heart failure. However, the molecular and cellular mechanisms that underlie this process remain elusive. Inadequate angiogenesis in the myocardium leads to a transition from cardiac hypertrophy to dysfunction, and our previous study showed that Ang II significantly impaired the angiogenesis response. The current study was designed to examine the role of Jagged1-Notch signaling in the effect of Ang II during impaired angiogenesis and cardiac hypertrophy.</p><p><b>METHODS</b>Ang II was subcutaneously infused into 8-week-old male C57BL/6 mice at a dose of 200 ng·kg-1·min-1 for 2 weeks using Alzet micro-osmotic pumps. N-[N-(3, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine tert-butyl ester (DAPT), a γ-secretase inhibitor, was injected subcutaneously during Ang II infusion at a dose of 10.0 mg·kg-1·d-1. Forty mice were divided into four groups (n = 10 per group): control group; Ang II group, treated with Ang II; DAPT group, treated with DAPT; and Ang II + DAPT group, treated with both Ang II and DAPT. At the end of experiments, myocardial (left ventricle [LV]) tissue from each experimental group was evaluated using immunohistochemistry, Western blotting, and real-time polymerase chain reaction. Data were analyzed using one-way analysis of variance test followed by the least significant difference method or independent samples t-test.</p><p><b>RESULTS</b>Ang II treatment significantly induced cardiac hypertrophy and impaired the angiogenesis response compared to controls, as shown by hematoxylin and eosin (HE) staining and immunohistochemistry for CD31, a vascular marker (P < 0.05 for both). Meanwhile, Jagged1 protein was significantly increased, but gene expression for both Jag1 and Hey1 was decreased in the LV following Ang II treatment, compared to that in controls (relative ratio for Jag1 gene: 0.45 ± 0.13 vs. 0.84 ± 0.15; relative ratio for Hey1 gene: 0.51 ± 0.08 vs. 0.91 ± 0.09; P < 0.05). All these cellular and molecular effects induced by Ang II in the hearts of mice were reduced by DAPT treatment. Interestingly, Ang II stimulated Hey1, a known Notch target, but did not affect the expression of Hey2, another Notch target gene.</p><p><b>CONCLUSIONS</b>A Jagged1-Hey1 signal might mediate the impairment of angiogenesis induced by Ang II during cardiac hypertrophy.</p>

A study on the relationship between medical students' social adaptability and their family education / 中华医学教育探索杂志

Objective To understand the situation of medical students' social adaptability and analyze its relationship with their family upbringing style.Methods A cross-sectional study was adopted,and the random sampling method was used to selected medical students as targeted population in a medical university in Jilin City.Parenting Style Assessment Scale and Social Adaptation Diagnostic Scale were applied to know the family rearing styles and social adaptability status of medical college students.Results Among the 198 responders,the proportion of good and strong social adaptability among medical college studies accounted for only 8.1％ (16) and 2.0％ (4);The social adaptation ability of the urban students and the only child students was higher than that of the rural and non only child students (P＜0.05);In parental rearing pattems,regardless of sex,whether students were the only child and where their census register was,emotional warmth and understanding were all positively correlated with medical students' social adaptation ability (P＜0.05),while refusal and denial were negatively correlated with medical students' social adaptation ability (P＜0.05);In addition,the punishment,severe over protection and other parenting styles also showed a certain degree of negative correlation with social adaptability(P＜0.05).Conclusion The social adaptability of medical students is poor,and their parenting styles was correlated with their social adaptation ability.Parents should give their children warmth and understanding,rather than rejection,denial,punishment,and overprotection,which will help to improve medical students' social adaptability.

Clinical features and operative treatment of traumatic cervical spinal fractures / 局解手术学杂志

Objective To analyze the clinical features and operative treatment of traumatic cervical spinal fractures in order to improve the prevention and surgical treatment.Methods A review of 324 cases of traumatic cervical spinal fractures admitted to general hospital of Shenyang military area command from January 2006 to December 2015 was performed to analyze their statistical epidemiology.Data included age,gender,etiologies of trauma,anatomical distribution,ASIA classification of neurological deficit and associated injuries.Results The ages of 324 patients ranged from 18 to 85 years,with a mean value of 43.8 years,70.4％ of all the patients (228/324) received operations,the 30 to 39 year-old patients formed the largest group,accounting for about 27.2％ (88/324).Combined cervical and other segments fracture accounting for about 8.0％ (26/324),among which combined cervical and thoracic spine fracture,combined cervical and lumbar spine fracture,combined cervical,thoracic and lumbar spine fracture accounted for 5.9％ (19/324),1.5％ (5/324),0.6％ (2/324) respectively.The frequency of neurological deficit (65.1％),frequency of complications (4.7 ％) was the largest in the ≥ 60 year-old patients group.The frequency of combined injuries(34.2％) was the largest in the 40 to 49 year-old patients group.High fall,road traffic accident and low fall were the most common etiologies,accounting for 34.6 ％ (112/324),32.1％ (104/324) and 18.8 ％ (61/324) respectively.The sex ratio (7.7 ％),frequency of neurological deficit (92.3％) and frequency of combined injuries (34.6％) were the largest in the patients caused by struck by object group.Among 228 patients who received operations,47 patients presented with ASIA A,12 patients with ASIA B,29 patients with ASIA C,63 patients with ASIA D and 77 patients with ASIA E before operation.After operations,46 patients presented with ASIA A,7 patients with ASIA B,23 patients with ASIA C,53 patients with ASIA D and 99 patients with ASIA E.There were 38 patients(16.7％) had got 1 to 2 grade recovery.Conclusion The epidemiological survey of traumatic cervical spinal fractures reveals that the 30 to 39 year-old patients and high fall was the most common age and etiology for injuries of cervical spinal fracture.The ≥60 year-old patients group and struck by object group presented with the highest frequency of neurological deficit,operation can improve the recovery of neurological deficit,the prevention and treatment should be designed according to the injury features of different individuals.

Infection prevention of new-type bulb syringe during posterior lumbar surgery / 医疗卫生装备

Objective To study the infection prevention effect of a new type of bulb syringe during posterior lumbar surgery, which can execute pulse irrigation continuously. Methods Totally 30 patients undergoing multi-level posterior lumbar interbody fusion surgery from June to December 2016 were divided into an experiment group and a control group. The experiment group applied the bulb syringe, and the control group used tipping irrigation. The two groups were compared on intraoperative irrigation time, the development trend of C-reactive protein (CRP) 1, 3 and 5 days after surgery, incidence of postoperative pyrexia, wound healing and suture-removal time. Results The experimental group had the intraoperative irrigation time being (2.13±0.15)min, which was significantly shorter than that [(5.59±1.24)min] in the control group. In the experimental group, the CRP measurement values 1, 3 and 5 days after surgery were 46, 19 and 5 mg/L respectively and showed adeclining trend;in the control group, the CRP measurement values 1, 3 and 5 days after surgery were 49, 52 and 61 mg/L respectively and showed an increasing trend. There were 3 cases of incision exudation in the control group while none in the experimental group. The experimental group had the suture-removal time being 11.57 d, which was statistically less than that (14.29 d) in the control group. The body temperature 3 and 5 days after surgery was (37.1±2.26) and (37.0±0.12)℃respectively in the experimental group while (38.2 ±3.34) and (37.5 ±0.25)℃in the control group, and there were obvious differences between the two groups (P<0.05). There were no infected incision occurred in the two groups. Conclusion The bulb syringe gains advantages over the traditional irrigation in easy operation, short time and incidence of infected incision, and thus is worthy promoting clinically.

Optimization of Extraction Technology of Panax Notoginseng and Scrophulariae Radix from Rupixiao Granule by Orthogonal Design / 中国药师

Objective: To optimize the extraction technology of Panax notoginseng and Scrophulariae radix from Rupixiao granule.Methods: With the dry extract rate and transfer rates of ginsenoside Rg1, ginsenoside Rb1 and harpagoside as the comprehensive index, the orthogonal design was adopted to investigate the effects of the amount and concentration of ethanol, extracting duration and times on the extraction technology.The contents of ginsenoside Rg1, ginsenoside Rb1 and harpagoside were determined by HPLC.Results: The optimal extraction technology was extracted twice with 8-fold amount of 60% ethanol with 2 h per time.The transfer rate of ginsenoside Rg1, ginsenoside Rb1 and harpagoside was (79.4%±1.56%), (42.62%±0.68%) and (44.89%±0.58%)(n=3), respectively.The dry extract rate was (20.99%±0.411%).Conclusion: The optimized extraction technology is stable and feasible, which can be used for extracting Panax notoginseng and Scrophulariae radix from Rupixiao granule.

Application of Polymeric Micelles in Transdermal Drug Delivery Systems / 中国药师

Objective: To review the application of polymeric micelles as the vehicles in transdermal delivery systems.Methods: Based on the recently published papers, the researches of preparation, penetration mechanism, drug release and application of polymeric micelles in transdermal delivery systems were classified and summarized.Results: Polymeric micelles were extensively applied as drug vehicles due to the ability of solubilization and transdermal absorption enhancement.Conclusion: Polymeric micelles can be used as promising vehicles in transdermal delivery systems, which show a good application prospect.

CT features of renal carcinoma associated with xp11 .2 translocations/TFE3 genes fusions / 实用放射学杂志

Objective To analyze the CT features of renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions (Xp11.2 RCC),and to improve the diagnostic accuracy.Methods Clinical data,CT imaging and pathological features of 12 cases with pathology proved Xp11.2 RCC were analyzed retrospectively.Results All the 12 cases were solid masses.11 cases were oval or quasi-circular,1 case was irregular.Tumors were iso-density or hyperdensity on CT plain scan images.The density was heterogene-ous,combined with necrosis in 11 cases and spotty or patchy calcification in 7 cases.After injection of contrast,moderate or obvious enhancement of tumors was found,1 case had retroperitoneal lymph node metastasis,1 case was found with mass formation in the re-nal hilus,1 case had adrenal metastasis.Another one was found with psoas major muscle and lumbar 5 invaded.Conclusion The Xp11 .2 RCC has certain CT characteristics.This disease should be considered when a renal tumor is iso-density or hyperdensity on the CT plain scan images and has moderate or obvious enhancement,combined with necrosis or calcification.

Progresses of cell-based therapy and tissue engineering in the treatment of age-related macular degeneration / 中华眼底病杂志

Age-related macular degeneration (AMD) has become one of the leading causes of irreversible blindness worldwide.With the advancement of stem cell technology,tissue engineering and biomaterials,cell-based therapy has been inspiring for many degenerative diseases.For its unique advantages,AMD has become one of the most promising fields for cell-based therapy,which involve retinal pigment epithelium(RPE)cells,induced differentiation of neural retina cells and related cytokine regulations.RPE cells can be derived from human embryonic stem cells (hESC) or Induced pluripotent stem cells (iPS).Recently hESC-derived RPE cells have been applied to patients with dry AMD with initial success in clinical trials.In terms of tissue engineering,studies are focused on factors affecting the long-term survival of transplanted cells,including tissue scaffolds,soluble hybrid materials and scaffold anchoring.This article briefly reviews the RPE differentiation,neural retina differentiation and related cytokines of cell-based therapy and scaffolds,materials,and cell-scaffolds interactions of tissue engineering in AMD treatment.