The number of investigator initiated research (IIR) is increasing. But the recognition and management of IIR in China is still in its infancy, and there is a lack of specific and operable guidance for the implementation process. Based on our practical experiences, previous literature reports, and current policy regulations, the authors took prospective IIR as an example to summarize the implementation process of IIR into 14 steps, which are as the following: study initiation, ethical review, study registration, study filing, case report form design, database establishment, standard operating procedure making, investigator training, informed consent, data collection, data entry, data verification, data locking and data archiving.

Abstract: Objective To elucidate the potential mechanism of Jindanjiangan Capsule in the treatment of liver fibrosis by network pharmacology and molecular docking. Methods Active ingredients and targets of Jindanjiangan Capsules were searched by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and HERB databases, and the disease targets were screened by DisGeNET and Therapeutic Target Database (TTD) databases. The targets of the active ingredients of Jindanjiangan Capsule were matched with the disease targets, and the common targets were imported into the String database platform to construct a protein-protein interaction network (PPI) network. CytoNCA tool of Cytoscape 3.9.1 software was used for topological analysis to screen key targets. Traditional Chinese Medicine-Key Active IngredientsKey Target Network was constructed by Cytoscape 3.9.1 Software. KEGG enrichment analysis of key targets was performed through the DAVID platform. The molecular docking of active ingredients and targets was performed to verify the above results using LeDock software. Results By screening, 180 potential active ingredients and 1 340 targets of Jindanjiangan Capsule and 1 060 targets of liver fibrosis, and 273 common targets were obtained. 29 key targets related to liver fibrosis were screened out by PPI network interaction, and verified by KEGG analysis and molecular docking. Jindanjiangan capsule acts on key targets such as EGFR, MMP9, PTGS2, ESR1, PIK3CA, F2, PPARG, and PTPN11 through active components such as isovitexin, quercetin 7-O- β -D-glucoside, (3S, 6S) -3- (benzyl) -6- (4-hydroxybenzyl) piperazine-2, 5-quinone, 6-Osyringoyl-8-O-acetylshanzhiside methyl ester, tanshinone II, nortanshinone, capillaris chromone, and etanone. The specific mechanism may be related to HIF-1 signaling pathway, C-type lectin receptor signaling pathway, Toll-like receptor signaling pathway, tumor necrosis factor signaling pathway, relaxin signaling pathway, FoxO signaling pathway and so on. Conclusion Jindanjiangan capsule can effectively treat hepatic fibrosis through multi-component, multi-target and multi-pathway.

OBJECTIVE: To explore the genetic basis for two Chinese pedigrees affected with Coffin-Siris syndrome (CSS). METHODS: Whole exome sequencing (WES) was carried out for the probands. Candidate variants were verified by Sanger sequencing of the probands and their family members. RESULTS: The two probands were respectively found to harbor a heterozygous c.5467delG (p.Gly1823fs) variant and a heterozygous c.5584delA (p.Lys1862fs) variant of the ARID1B gene, which were both of de novo in origin and unreported previously. Based on the guidelines of American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION The c.5467delG (p.Gly1823fs) and c.5545delA (p.Lys1849fs) variants of the ARID1B genes probably underlay the CSS in the two probands. Above results have enabled genetic counselling and prenatal diagnosis for the pedigrees.
Abnormalities, Multiple ; China ; DNA-Binding Proteins/genetics* ; Face/abnormalities* ; Hand Deformities, Congenital ; Humans ; Intellectual Disability ; Micrognathism ; Neck/abnormalities* ; Pedigree ; Transcription Factors/genetics*

Objective:To assess the influence of age on the safety of propofol mono-sedation for adult patients undergoing painless gastroscopy.Methods:A retrospective study was conducted on data of 321 patients scheduled for painless gastroscopy with propofol mono-sedation. According to the age, patients were divided into youth group (116 cases, 18-44 years), middle-aged group (103 cases, 45-59 years) and elderly group (102 cases, 60-80 years). The procedure time, the total dosage of propofol, the occurrence of airway obstruction or hypoxemia, the use of airway interventions including airway opening maneuvers and facemask ventilation, lowest SpO 2, adverse cardiovascular events (including hypertension, hypotension, tachycardia, and bradycardia), and the use of ephedrine during painless gastroscopy were observed. Results:There was significant difference regarding the total dosage of propofol among youth group (173.2±47.0 mg), middle-aged group (158.8±41.3 mg) and elderly group (137.8±26.3 mg) ( F=21.761, P<0.001). The total dosage of propofol was significantly lower in the elderly group compared with the middle-aged group ( P<0.017) and youth group ( P<0.017), and that in the middle-aged group was significantly lower than that in the youth group ( P<0.017). The incidence of hypoxemia was 12.9% (15/116) in the youth group, 15.5% (16/103) in the middle-aged group and 25.5% (26/102) in the elderly group, with significant difference among three groups ( χ2=5.711, P=0.017). Moreover, the incidence of hypoxemia was significantly higher in the elderly group compared with the middle-aged group ( P<0.017) and youth group ( P<0.017). The incidences of hypotension, bradycardia and total adverse cardiovascular events were 5.2% (6/116), 4.9% (5/103) and 11.8% (12/102), 1.7% (2/116), 2.9% (3/103) and 7.8% (8/102), and 11.2% (13/116), 10.7% (11/103) and 20.6% (21/102) respectively in youth, the middle-aged and the elderly group. There were no significant differences in the above indicators among the three groups ( P>0.05). However, compared with those of the young and the middle-aged patients, the occurrence of hypotension, bradycardia and total adverse cardiovascular events in the elderly patients were on the rise. There were no significant differences among the three groups in other indices( P>0.05). Conclusion:Total dosage of propofol may need to be decreased gradually with the increase of age of patients undergoing gastroscopy with propofol mono-sedation. Compared with young and middle-aged patients, elderly patients have a significantly higher incidence of hypoxemia, with a tendancy of total adverse cardiovascular events increase, so the safety of painless gastroscopy is reduced for these patients.

Objective To analyze the efficacy and safety of nalbuphine in patients with sedative analgesia in intensive care unit (ICU). Methods A prospective observation was conducted. The adult patients with mild and moderate analgesia in general ICU of the First Affiliated Hospital of Zhengzhou University from January to November in 2017 were enrolled, and they were divided into nalbuphine group and sufentanil group in proper order. The nabobrown group was given 40 mg nabobrown, the sufentanil group was given 0.1 mg sufentanil, both of which were injected with 50 mL normal saline for continuous intravenous infusion in micro-pump. Infusion speed was checked according to pain level. The analgesic target was critical-care pain observation tool (CPOT) score < 2. The change in hemodynamics of patients in both groups were observed, and CPOT score and Richmond agitation-sedation scale (RASS) score were recorded before and l, 3, 5, 12, 24 hours after administration. The analgesic and sedative effects of two drugs were evaluated. Results A total of 141 patients were enrolled, including 71 patients in nalbuphine group and 70 in sufentanil group. There was no significant difference in general data including gender, age, body weight, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) or pain source, as well as baseline hemodynamics parameter between the two groups. At 1 hour and 3 hours after administration, nalbuphine had no effect on blood pressure, but the heart rate was decreased slightly, while the heart rate and blood pressure of the sufentanil group were decreased obviously. The two drugs could make the heart rate and blood pressure fluctuate obviously with the time of medication, but there was no statistical difference between the two drugs. The two drugs had no significant effect on pulse oxygen saturation (SpO2) during analgesia. The average dosage of nalbuphine was 0.03 (0.02, 0.05) mg·kg-1·h-1in the nalbuphine group, and the patient was satisfied with the analgesic effect until 3 hours after the use of the drug, and CPOT score was significantly decreased as compared with that before administration [1.0 (1.0, 2.0) vs. 3.0 (2.0, 4.0), P < 0.01], and the sedative effect was increased, RASS score was significantly lower than that before administration [0 (0, 1.0) vs. 1.0 (1.0, 2.0), P < 0.01]. No patients in naporphine group were treated with sufentanil due to unsatisfactory analgesia. The average dosage was 0.11 (0.06, 0.14) μg·kg-1·h-1in the sufentanil group, the patient was satisfied with the analgesic effect until 5 hours after administration, and the CPOT score was significantly lower than that before administration [1.0 (1.0, 2.0) vs. 4.0 (3.0, 6.0), P < 0.01], and the sedative effect was significantly increased, RASS score was significantly lower than that before administration [0 (-1.0, 0) vs. 2.0 (1.0, 2.0), P < 0.01]. The scores of CPOT and RASS in the sufentanil group were significantly higher than those of the naporphine group before use, so the decrease in the CPOT and RASS scores of the two drugs was further analyzed, which indicated the decrease in CPOT score of naporphine group was significantly lower than that in sufentanil group from 3 hours on [1.0 (0, 2.0) vs. 2.0 (1.0, 3.0), P < 0.05], and the decrease in RASS score of naporphine group was significantly lower than that in sufentanil group from 1 hour on [0 (0, 1.0) vs. 1.0 (0, 2.0), P < 0.01]. It suggested that naporphine could achieve sustained and stable analgesic effect and avoid excessive sedation caused by sufentanil. Conclusions Naporphine had a sustained and stable analgesic effect on patients with mild and moderate ICU analgesia. The onset time of naporphine was equivalent to sufentanil, and it had a certain sedative effect and less influence on hemodynamics.

Goose hemorrhagic polyomavirus (GHPV) is not a naturally occurring infection in geese in China; however, GHPV infection has been identified in Pekin ducks, a domestic duck species. Herein, we investigated the prevalence of GHPV in five domestic duck species (Liancheng white ducks, Putian black ducks, Shan Sheldrake, Shaoxing duck, and Jinyun Sheldrake) in China. We determined that the Jinyun Sheldrake duck species could be infected by GHPV with no clinical signs, whereas no infection was identified in the other four duck species. We sequenced the complete genome of the Jinyun Sheldrake origin GHPV. Genomic data comparison suggested that GHPVs share a conserved genomic structure, regardless of the host (duck or geese) or region (Asia or Europe). Jinyun Sheldrake origin GHPV genomic characterization and epidemiological studies will increase our understanding of potential heterologous reservoirs of GHPV.
China ; Ducks ; Epidemiologic Studies ; Geese ; Genome ; Polyomavirus ; Prevalence

Objective To assess the bone tunnel area at different times and sites of the tunnel after the anterior cruciate ligament(ACL) reconstruction in rabbits using Micro-CT.Methods Fifteen rabbits were performed ACL reconstruction using semitendinosus tendon autograft and randomly allocated into 3 groups and killed at 3,6,and 12 weeks after the operation.All samples undertook the micro-CT scanning(using SkyScan 1176,Bruker,U.S.A.) and were analyzed the areas of bone tunnels of femur and tibia after the 3-demension image rebuilding.For each tunnel,the area of the entrance,middle and exit of the tunnel were measured 3 times respectively and compared.Results The average area of the femoral tunnel did not change significantly with time,being 4.84 mm2,4.57 mm2 and 4.46 mm2 at 3,6 and 12 weeks after the operation(P=0.99).At the very beginning,the femoral tunnel area at the entrance was the biggest,while that of the middle was the smallest.Six weeks after the operation,significant differences were observed between the femoral tunnel area at the entrance and middle,as well as that between the exit and middle(P=0.0011,P=0.0106);However,12 weeks after the operation,significant differences were observed only between that at the entrance and middle(P=0.0227).The average tibial tunnel area increased significantly at 6 weeks(6.577 mm2) and decreased at 12 weeks(3.103 mm2) after the operation(P=0.0005).Moreover,no significant differences were observed in the average tibial tunnel area at different time points and sites(P＜0.05).At different sites,the average tibial tunnel area expanded at 6 weeks,and then declined at 12 weeks after the operation.Conclusion The bone tunnel area changes with time after the ACL reconstruction,first increasing followed by decreasing in the average tibial tunnel area.The femur and tibial tunnel have significant differences in the tunnel area at different sites,which change differently with time.The bone tunnel expansion after the anterior cruciate ligament reconstruction can be comprehensively measured repeatedly at different sites.

Background and objective hTe development of image technology has led to increasing detection of pulmonary small nodules year by year, but the determination of their nature before operation is diffcult. hTis clinical study aimed to investigate the necessity and feasibility of surgical resection of pulmonary small nodules through a minimally invasive approach and the operational manner of non-small cell lung cancer (NSCLC). Methods hTe clinical data of 129 cases with pulmonary small nodule of 10 mm or less in diameter were retrospectively analyzed in our hospital from December 2013 to November 2016. hTin-section computed tomography (CT) was performed on all cases with 129 pulmonary small nodules. CT-guided hook-wire precise localization was performed on 21 cases. Lobectomy, wedge resection, and segmentectomy with lymph node dissection might be performed in patients according to physical condition. Results Results of the pathological examination of 37 solid pulmonary nodules (SPNs) revealed 3 primary squamous cell lung cancers, 3 invasive adenocarcino-mas (IAs), 2 metastatic cancers, 2 small cell lung cancers (SCLCs), 16 hamartomas, and 12 nonspeciifc chronic inlfammations. hTe results of pathological examination of 49 mixed ground glass opacities revealed 19 IAs, 6 micro invasive adenocarcinomas (MIAs), 4 adenocarcinomas in situ (AIS), 1 atypical adenomatous hyperplasia (AAH), 1 SCLC, and 18 nonspeciifc chronic in-lfammations. hTe results of pathological examination of 43 pure ground glass opacities revealed 19 AIS, 6 MIAs, 6 IA, 6 AAHs, and 6 nonspeciifc chronic inlfammations. Wedge resection under video-assisted thoracoscopic surgery (VATS) was performed in patients with 52 benign pulmonary small nodules. Lobectomy and systematic lymph node dissection under VATS were performed in 33 patients with NSCLC. Segmentectomy with selective lymph node dissection, wedge resection, and selective lymph node dissection under VATS were performed in six patients with NSCLC. Two patients received secondary lobectomy and systematic lymph node dissection under VATS because of intraoperative frozen pathologic error that happened in six cases. Two cases of N2 lymph node metastasis were found in patients with SPN of IA. Conclusion Positive surgical treatment should be taken on patients with persistent pulmonary small nodules, especially ground glass opacity, because they have a high rate of malignant lesions. During the perioperative period, surgeons should fully inform the patients and family members that error exist in frozen pathologic results to avoid medical disputes.

OBJECTIVETo determine the effect of aspirin on cell proliferation, alkaline phosphatase (ALP) activity, cell cycle and apoptosis in murine bone marrow stromal cells, so as to explore an appropriate dose range to improve bone regeneration in periodontal treatment.

METHODSST2 cells were stimulated with aspirin (concentrations of 1, 10, 100 and 1 000 μmol/L) for 1, 2, 3, 5 and 7 d. Cell proliferation was measured by methyl thiazolyl tetrazolium (MTT) assay. After ST2 cells were treated for 1, 3 and 7 d, ALP activity was measured by ALP kit, cell cycle and apoptosis were measured by flow cytometry (FCM) after treated for 48 h.

RESULTSMTT assays showed that various doses of aspirin have different effects on the cell growth. Briefly, lower concentrations (1, 10 μmol/L) of aspirin promoted the cell growth, the A value of 0, 1 and 10 μmol/L aspirin 7-day-treated cells were 0.313±0.012, 0.413±0.010 and 0.387±0.017 respectively (P <0.01 vs control), and so did the ALP level ([4.3±0.9], [6.0±0.3] and [7.7±0.4] μmol·min(-1)·g(-1), P <0.05 vs control), while higher concentrations, especially 1000 μmol/L of aspirin might inhibit the cell growth with time going, A value and ALP level were 0.267±0.016, (4.3±1.3) μmol·min(-1)·g(-1) respectively (P <0.05 vs control). Cell cycle analysis revealed no changes in comparison to control cells after treatment with 1 or 10 μmol/L aspirin, but it was observed that cell mitosis from S phase to G2/M phase proceeded at higher concentrations of 100 μmol/L aspirin, and the cell cycle in phase G0/G1 arrested at 1000 μmol/L. Parallel apoptosis/necrosis studies showed that the percentage of cells in apoptosis decreased dramatically at all doses of aspirin, the apoptosis rates of ST2 cells responded to 0, 1, 10, 100 and 1000 μmol/L aspirin were (11.50±0.90)%, (5.30±0.10)%, (5.50±0.10)%, (4.90±0.90)% and (7.95±0.25)% respectively (P<0.05 vs control).

CONCLUSIONSThis study demonstrated that lower dosage of aspirin can promote ST2 cells growth, osteogenic activity and inhibit its apoptosis. Aspirin maybe used for the bone reconstruction with a proper concentration.

Alkaline Phosphatase ; metabolism ; Animals ; Apoptosis ; drug effects ; Aspirin ; administration & dosage ; pharmacology ; Bone Regeneration ; Cell Cycle ; drug effects ; Cell Division ; Cell Line, Tumor ; Cell Proliferation ; Flow Cytometry ; Formazans ; Mesenchymal Stromal Cells ; cytology ; drug effects ; enzymology ; Mice ; Periodontics ; Tetrazolium Salts ; Time Factors

Objective To analyze the population distribution and clinical characteristics of esophageal cancer in Luzhou prefecture of Sichuan. Methods The data of 690 cases of resected specimens with esophageal cancer from October 2010 to September 2014 were analyzed retrospectively, including 659 cases of esophageal squamous cell carcinoma, 10 cases of adenocarcinoma, 7 cases of adenosquamous carcinoma, 5 cases of sarcomatoid carcinoma, 2 cases of carcinoma in situ, 3 cases of leiomyosarcoma, 2 cases of small cell carcinoma, 1 case of undifferentiated carcinoma and 1 case of mixed carcinoma. Results The constituent ratio of 51-60 years old population of 690 cases with esophageal cancer was the highest for 40.00%(276/690). In≤60 years patients, the rate of esophageal cancer in male was higher than that in female: 56.15%(338/602) vs. 34.09%(30/88), χ2 = 15.005, P =0.000. Clinical pathological factors of lymph node metastasis showed that there were statistically significant differences between male and female: 45.68%(275/602) vs. 34.09%(30/88), χ2 = 4.182, P =0.041;the lower the position, the higher the lymph nodes metastasis rate:the lymph nodes metastasis rate in superior segment, middle segment, inferior segment was 32.00%(8/25), 41.22%(216/524) and 57.45%(81/141),χ2=13.425, P=0.001;the lower the differentiation, the higher the lymph nodes metastasis rate:the lymph nodes metastasis rate in high, middle and lower differentiation was 40.84%(165/404), 47.60%(109/229) and 75.76%(25/33), χ2 = 16.065, P = 0.000. The lymph nodes metastasis rate in different general types and histology types had no significant differences(P>0.05). Conclusions The incidence rate of esophageal cancer in male is significantly higher than that in female, the higher the lymph node metastasis rate, the lower the position and the differentiation of esophageal cancer in Luzhou prefecture of Sichuan.