Purpose To evaluate the feasibility of droplet digital PCR(ddPCR)for gene fusion detection of neurotrophic receptor kinase(NTRK).Methods A total of 830 cases of primary colorectal adenocarcinoma(CRAC)and 560 cases of gastric adenocarcinoma(GAC)were retrospectively studied.Im-munohistochemistry(IHC)and fluorescence in situ hybridization(FISH)were used to detect pan-TRK protein expression and NTRK1/2/3 gene fracture in formalin-fixed paraffin-embedded(FFPE)tumor tissues,respectively.FISH or IHC positive sam-ples were further detected by next generation sequencing and ddPCR.Results All FFPE samples were tested successfully by IHC and FISH methods.A total of 26 samples with NTRK gene breaks or pan-TRK expression were detected by IHC,among these 26 cases,21 FISH were positive and 18 IHC positive.A total of 14 cases of NTRK fusion and 2 cases of amplification were detected by DNA sequencing.A total of 3 cases carrying NTRK gene fusion were detected by RNA sequencing,and the results of ddPCR were completely consistent with RNA sequen-cing.Conclusion ddPCR can effectively distinguish false posi-tive CRAC and GAC cases harboring NTRK fusion detected by FISH and DNA sequencing,which can be used as the effective method for screening NTRK gene fusion.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Inflammatory bowel disease is a chronic non-specific intestinal inflammatory disease. Biological agents have good clinical efficacy, but some patients may stop treatment due to adverse reactions. New oral small molecule drugs have the characteristics of small molecular weight, easier passage through cell membrane and short half-life, and have good curative effect on IBD. This article reviews the research progress of small molecule drugs for the treatment of IBD, in order to guide clinical application.

Inflammatory bowel disease is a chronic non-specific intestinal inflammatory disease. Biological agents have good clinical efficacy, but some patients may stop treatment due to adverse reactions. New oral small molecule drugs have the characteristics of small molecular weight, easier passage through cell membrane and short half-life, and have good curative effect on IBD. This article reviews the research progress of small molecule drugs for the treatment of IBD, in order to guide clinical application.

Patients with non-small cell lung cancer (NSCLC) are treated in a variety of ways. In addition to radiotherapy, chemotherapy and targeted therapy, breakthroughs have been made in immune checkpoint inhibitors, in particular, programmed cell death 1 (PD-1) and its ligand (PD-L1) inhibitors have achieved survival benefits for NSCLC patients, and some of them have been approved as first-line drugs by the US Food and Drug Administration. Currently, commonly used PD-L1 inhibitors are atezolizumab, durvalumab and avelumab. Combination therapies include combination with chemotherapy, anti-vascular endothelial growth factor drugs, molecular targeted therapy and immunotherapy.

OBJECTIVE: To analyze the current status of diagnosis and management of acute appendicitis (AA) in China. METHODS: Questionnaire survey was used to retrospectively collect data of hospitalized patients with AA from 43 medical centers nationwide in 2017 (Sort by number of cases provided: Jinling Hospital of Medical School of Nanjing University, The First Affiliated Hospital of Xinjiang Medical University, Lu'an People's Hospital, Tengzhou Central People's Hospital, Dalian Central Hospital, The Affiliated Hospital of Xuzhou Medical University, Dongying People's Hospital, Jinjiang Hospital of Traditional Chinese Medicine, Huangshan Shoukang Hospital, Xuyi People's Hospital, Nanjing Jiangbei People's Hospital, Lanzhou 940th Hospital of PLA, Heze Municipal Hospital, The First College of Clinical Medical Science of China Three Gorges University, Affiliated Jiujiang Hospital of Nanchang University, The Second People's Hospital of Hefei, Affiliated Central Hospital of Shandong Zaozhuang Mining Group, The Third People's Hospital of Kunshan City, Xuzhou First People's Hospital, The 81st Group Army Hospital of PLA, Linyi Central Hospital, The General Hospital of Huainan Eastern Hospital Group, The 908th Hospital of PLA, Liyang People's Hospital, The 901th Hospital of Joint Logistic Support Force, The Third Affiliated Hospital of Chongqing Medical University, The Fourth Hospital of Jilin University, Harbin Acheng District People's Hospital, The First Affiliated Hospital of Zhengzhou University, Nanjing Luhe People's Hospital, Taixing Municipal People's Hospital, Baotou Central Hospital, The Affiliated Hospital of Nantong University, Linyi People's Hospital, The 72st Group Army Hospital of PLA, Zaozhuang Municipal Hospital, People's Hospital of Dayu County, Taixing City Hospital of Traditional Chinese Medicine, Suzhou Municipal Hospital, Beijing Guang'anmen Hospital, Langxi County Hospital of Traditional Chinese Medicine, Nanyang Central Hospital, The Affiliated People's Hospital of Inner Mongolia Medical University).The diagnosis and management of AA were analyzed through unified summary. Different centers collected and summarized their data in 2017 and sent back the questionnaires for summary. RESULTS: A total of 8 766 AA patients were enrolled from 43 medical centers, including 4 711 males (53.7%) with median age of 39 years and 958 (10.9%) patients over 65 years old. Of 8 776 patients, 5 677 cases (64.6%) received one or more imaging examinations, and the other 3 099 (35.4%) did not receive any imaging examination. A total of 1 858 (21.2%) cases received medical treatment, mainly a combination of nitroimidazoles (1 107 cases, 59.8%) doublet regimen, followed by a single-agent regimen of non-nitroimidazoles (451 cases, 24.4%), a nitroimidazole-free doublet regimen (134 cases, 7.2%), a triple regimen of combined nitroimidazoles (116 cases, 6.3%), nitroimidazole alone (39 cases, 2.1%) and nitroimidazole-free triple regimen (3 cases, 0.2%). Of the 6 908 patients (78.8%) who underwent surgery, 4 319 (62.5%) underwent laparoscopic appendectomy and 2589 (37.5%) underwent open surgery. Ratio of laparotomy was higher in those patients under 16 years old (392 cases) or over 65 years old (258 cases) [15.1%(392/2 589) and 10.0%(258/2 589), respectively, compared with 8.5%(367/4 316) and 8.0%(347/4 316) in the same age group for laparoscopic surgery, χ²=91.415, P<0.001; χ²=15.915,P<0.001]. Patients with complicated appendicitis had higher ratio of undergoing open surgery as compared to those undergoing laparoscopic surgery [26.7%(692/2 589) vs. 15.6%(672/4 316), χ²=125.726, P<0.001].The cure rates of laparoscopic and open surgery were 100.0% and 99.8%(2 585/2 589) respectively without significant difference (P=0.206). Postoperative complication rates were 4.5%(121/2 589) and 4.7%(196/4 316) respectively, and the difference was not statistically significant (χ²=0.065, P=0.799). The incidence of surgical site infection was lower (0.6% vs. 1.7%, χ²=17.315, P<0.001), and hospital stay was shorter [6(4-7) days vs. 6(5-8) days, U=4 384 348.0, P<0.001] in the laparoscopic surgery group, while hospitalization cost was higher (median 12 527 yuan vs. 9 342 yuan, U=2 586 809.0, P<0.001). CONCLUSIONS The diagnosis of acute appendicitis is still clinically based, supplemented by imaging examination. Appendectomy is still the most effective treatment at present. Laparoscopic appendectomy has become the main treatment strategy, but anti-infective drugs are also very effective.
Acute Disease ; Adolescent ; Adult ; Aged ; Anti-Bacterial Agents ; therapeutic use ; Appendectomy ; Appendicitis ; diagnosis ; therapy ; China ; Female ; Health Care Surveys ; Humans ; Laparoscopy ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

Objective To explore the effects of program of pinyin game on children with attention deficit hyperactivity disorder (ADHD) and reading disorder by a randomized controlled trial.Methods Thirty-one cases diagnosed as ADHD according to the criteria of DSM-Ⅳ and comorbid reading disorder were involved in the study.The ADHD and reading disorder children were divided into the intervention group (n=17) and the control group (n=14) by simple random sampling.One of them accepted program of pinyin game training and the other group did not make an intervention.Phonological awareness test,phonetic recognition test and reading ability test were used to evaluate the reading ability of two groups at baseline and the end of week 8,and to make intra-group and inter-group comparisons.Results At baseline,there was no significant difference in reading ability scores between the intervention group and the control group.The scores of the Phoneme deletion (4.9± 1.9 vs.5.9±2.0),Cut pinyin word (37.5(14.0,79.0) vs.50.0(17.0,99.0)),significantly increased after the intervention by the pinyin game learning software in week 8,but there was no significant difference between the two groups(t=-2.248,P=0.043;Z--3.06,P=0.002).Conclusion The intervention effect of the ADHD comorbidity reading disorder group after 8 weeks of program of pinyin game training was not significantly better than that of the control group,but it may improve the children's phonetic awareness and pinyin recognition ability.

Objective To explore the effects of program of pinyin game on children with attention deficit hyperactivity disorder (ADHD) and reading disorder by a randomized controlled trial.Methods Thirty-one cases diagnosed as ADHD according to the criteria of DSM-Ⅳ and comorbid reading disorder were involved in the study.The ADHD and reading disorder children were divided into the intervention group (n=17) and the control group (n=14) by simple random sampling.One of them accepted program of pinyin game training and the other group did not make an intervention.Phonological awareness test,phonetic recognition test and reading ability test were used to evaluate the reading ability of two groups at baseline and the end of week 8,and to make intra-group and inter-group comparisons.Results At baseline,there was no significant difference in reading ability scores between the intervention group and the control group.The scores of the Phoneme deletion (4.9± 1.9 vs.5.9±2.0),Cut pinyin word (37.5(14.0,79.0) vs.50.0(17.0,99.0)),significantly increased after the intervention by the pinyin game learning software in week 8,but there was no significant difference between the two groups(t=-2.248,P=0.043;Z--3.06,P=0.002).Conclusion The intervention effect of the ADHD comorbidity reading disorder group after 8 weeks of program of pinyin game training was not significantly better than that of the control group,but it may improve the children's phonetic awareness and pinyin recognition ability.

Objective? To explore the effects of enhanced recovery after surgery (ERAS) intervention on functional rehabilitation among patients with anterior cruciate ligament (ACL) reconstruction under arthroscope. Methods? From January 2013 to April 2016, we selected 120 patients with ACL reconstruction under arthroscope in Department of Orthopedics in West China Hospital of Sichuan University by convenience sampling. All of the patients were divided into two groups according to the admission time including control group (n=60, traditional rehabilitation) and observation group (n=60, ERAS intervention). We compared the ankle swelling, effusion and the knee flexion as well as knee rehabilitation effect of patients in two groups with the Judet score and the Lysholn score after surgery. Results? The early ankle swelling of patients in observation group was more obvious than that in control group, and there were 12 cases with joint puncture drainage after surgery in observation group and 5 cases in control group with no statistical difference (χ2=3.358, P=0.067). There were 6 cases with knee functional disorder after surgery in control group reaching the excellent knee function after manual release. The excellent rates of knee function activity in observation group were respectively 83.33% and 96.67% three and six months after surgery superior than those (58.33% and 83.33%) in control group with statistical differences (χ2=9.076, 5.926; P＜0.05). The excellent rates of scores of knee function in observation group were respectively 80.00%, 91.67% three and six months after surgery higher than those (56.67% and 78.33%) in control group with statistical differences (χ2=7.548, 4.183;P＜ 0.05). Conclusions? The application of ERAS intervention in ACL reconstruction under arthroscope can effectively improve early function and scope of activity of knee, however the complications may occur, such as ankle swelling and effusion.

OBJECTIVETo summarize the treatment status of gastric gastrointestinal stromal tumor (GIST) in Shandong province,by analyzing the clinicopathological features and prognostic factors.

METHODSClinicopathological and follow-up data of 1 165 patients with gastric GIST between January 2000 and December 2013 from 23 tertiary referral hospitals in Shandong Province were collected to establish a database. The risk stratification of all cases was performed according to the National Institutes of Health(NIH) criteria proposed in 2008. Kaplan-Meier method was used to calculate the survival rate. Log-rank test and Cox regression model were used for univariate and multivariate prognostic analyses.

RESULTSAmong 1 165 cases of gastric GIST, 557 were male and 608 were female. The median age of onset was 60 (range 15-89) years. Primary tumors were located in the gastric fundus and cardia in 623 cases(53.5%), gastric body in 346 cases(29.7%), gastric antrum in 196 cases(16.8%). All the cases underwent resection of tumors, including endoscopic resection (n=106), local resection (n=589), subtotal gastrectomy(n=399), and total gastrectomy(n=72). Based on the NIH risk stratification, there were 256 cases (22.0%) at very low risk, 435 (37.3%) at low risk, 251 cases (21.5%) at intermediate risk, and 223 cases (19.1%) at high risk. A total of 1 116 cases(95.8%) were followed up and the median follow-up period was 40 (range, 1-60) months. During the period, 337 patients relapsed and the median time to recurrence was 34 (range 1-60) months. The 1-, 3-, and 5-year survival rates were 98.6%, 86.1% and 73.4%, respectively. The 5-year survival rates of patients at very low, low, intermediate, and high risk were 93.1%, 85.8%, 63.0% and 42.3% respectively, with a statistically significant difference (P=0.000). Multivariate analysis showed that primary tumor site (RR=0.580, 95%CI:0.402-0.835), tumor size (RR=0.450, 95%CI:0.266-0.760), intraoperative tumor rupture(RR=0.557, 95%CI:0.336-0.924), risk classification (RR=0.309, 95%CI:0.164-0.580) and the use of imatinib after surgery (RR=1.993, 95%CI:1.350-2.922) were independent prognostic factors.

CONCLUSIONSThe choice of surgical procedure for gastric GIST patients should be based on tumor size. All the routine procedures including endoscopic resection, local excision, subtotal gastrectomy and total gastrectomy can obtain satisfactory curative outcomes. NIH classification has a high value for the prediction of prognosis. Primary tumor site, tumor size, intraoperative tumor rupture, risk stratification and postoperative use of imatinib are independent prognostic factors in gastric GIST patients.