Lots of problems has exposed in medical system,especially in unreasonable utilization of health resources.This article,from the viewpoint of utilization of health resource,analyzes current problems and countermeasures of the reasonable utilization of health resources.

Neurogenesis is a process in which the neuronal stem cells differentiate into functional neurons including the cell proliferation,differentiation and migration.Previously,it was believed that neurogenesis is a prenatal process and the adult ependymal cells are incapable of regeneration.Now it is clear that mammalian brain retains the ability to generate new ceils in specific regions.One of the regions is subventricular zone of the lateral ventricles,new generated neurons and glial cells later migrate to olfactory and repair dysosmia through the RMS road.Here we will review the advances in adult neurogenesis in mammal subventficular zone.

The previous pharmacokinetic methods can be only limited to drug analysis in vitro, which provide less information on the distribution and metabolismof drugs, and limit the interpretation and assessment of pharmacokinetics, the determination of metabolic principles, and evaluation of treatment effect. The objective of the study was to investigate the pharmacokinetic characteristics of gene recombination angiogenesis inhibitor Kringle 5 in vivo. The SPECT/CT and specific 131I-Kringle 5 marked by Iodogen method were both applied to explore the pharmacokinetic characteristics of 131I-Kringle 5 in vivo, and to investigate the dynamic distributions of 131I-Kringle 5 in target organs. Labeling recombinant angio-genesis inhibitor Kringle 5 using 131I with longer half-life and imaging in vivo using SPECT instead of PET, could overcome the limitations of previous methods. When the doses of 131I-Kringle 5 were 10.0, 7.5 and 5.0 g/kg, respectively, the two-compartment open models can be determined within all the metabolic process in vivo. There were no significant differences in t1/2α, t1/2β, apparent volume of distribution and CL between those three levels. The ratio of AUC(0 ? 1) among three different groups of 10.0, 7.5 and 5.0 g/kg was 2.56:1.44:1.0, which was close to the ratio (2:1.5:1.0). It could be clear that in the range of 5.0–10.0 g/kg, Kringle 5 was characterized by the first-order pharmacokinetics. Approximately 30 min after 131I-Kringle 5 was injected, 131I-Kringle 5 could be observed to concentrate in the heart, kidneys, liver and other organs by means of planar imaging and tomography. After 1 h of being injected, more radionuclide retained in the bladder, but not in intestinal. It could be concluded that 131I-Kringle 5 is mainly excreted through the kidneys. About 2 h after the injection of 131I-Kringle 5, the radionuclide in the heart, kidneys, liver and other organs was gradually reduced, while more radionuclide was concentrated in the bladder. The radionuclide was completely metabolized within 24 h, and the distribution of radioactivity in rats was similar to normal levels. In our study, the specific marker 131I-Kringle 5 and SPECT/CT were suc-cessfully used to explore pharmacokinetic characteristics of Kringle 5 in rats. The study could provide a new evaluation platform of the specific, in vivo and real-time functional imaging and pharmacokinetics for the clinical application of 131I-Kringle 5.

OBJECTIVETo evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for gastrointestinal disorders.

METHODSRetrospective analysis of the clinical data of 406 patients who underwent FMT from May 2014 to April 2016 in the Intestinal Microenvironment Treatment Centre of Nanjing General Hospital was performed, including patients with constipation(276 cases), recurrent Clostridium Difficile infection (RCDI, 61 cases), ulcerative colitis(44 cases), irritable bowel syndrome (15 cases) and Crohn's disease(10 cases). Donors were completely unrelated, 18- to 50-year-old non-pregnant healthy adult, with healthy lifestyle and habits, without taking antibiotics, probiotics and other probiotics history within 3 months. There were three routes of FMT administration: patients received 6 days of frozen FMT by nasointestinal tube placed in the proximal jejunum under gastroscope (319 cases); patients received capsules FMT per day for 6 consecutive days (46 cases) or once 600 ml of treated fecal liquid infusion into colon and terminal ileum by colonoscopy(41 cases).

RESULTSClinical cure rate and improvement rate of different diseases receiving FMT were respectively as follows: RCDI was 85.2% (52/61) and 95.1%(58/61); constipation was 40.2%(111/276) and 67.4%(186/276); ulcerative colitis was 34.1%(15/44) and 68.2% (30/44); irritable bowel syndrome was 46.7% (7/15) and 73.3% (11/15) and Crohn disease was 30.0%(3/10) and 60.0%(6/10). RCDI had the best efficacy among these diseases(P<0.01). There was no significant difference between the three routes of FMT administration(P=0.829). The clinical cure rate and improvement rate of different routes were 43.3%(138/319) and 58.6% (187/319) respectively in nasogastric transplantation group, 41.5%(17/41) and 61.0%(25/41) in colonoscopy group, 37.0%(17/46) and 63.0% (29/46) in the capsule transplantation group. There was no serious adverse event during the follow-up. The most common side effects were respiratory discomfort (27.3%, 87/319) and increased venting (51.7%, 165/319) in nasogastric transplantation group. Diarrhea was the most common complication in colonoscopy group (36.6%, 15/41). The main symptoms were increased venting (50.0%, 23/46) and nausea(34.8%, 16/46) in oral capsule group. Side effect symptoms disappeared after the withdraw of nasogastric tube, or at the end of treatment, or during hospitalization for 1-3 days.

CONCLUSIONSFMT is effective for many gastrointestinal disorders. No significant adverse event is found, while the associated mechanism should be further explored.

Adult ; Clostridium Infections ; drug therapy ; Clostridium difficile ; drug effects ; Colitis, Ulcerative ; drug therapy ; Colonoscopy ; adverse effects ; methods ; Constipation ; drug therapy ; Crohn Disease ; drug therapy ; Diarrhea ; chemically induced ; Fecal Microbiota Transplantation ; methods ; statistics & numerical data ; Female ; Flatulence ; chemically induced ; Gastrointestinal Diseases ; drug therapy ; Gastroscopy ; methods ; Humans ; Intubation, Gastrointestinal ; adverse effects ; methods ; Irritable Bowel Syndrome ; drug therapy ; Male ; Middle Aged ; Nausea ; chemically induced ; Retrospective Studies ; Treatment Outcome

Objective:To observe the expression of deleted in malignant brain tumor protein 1 (DMBT1) in rat acute respiratory distress syndrome (ARDS) model induced by sepsis and its relationship with ARDS related biomarkers.Methods:Forty-eight healthy male rats were randomly divided into sham operation group (Sham group) and ARDS model group, and the rats in each group were further divided into three subgroups at 6, 12 and 24 hours after operation, with 8 rats in each subgroup. The rats in the Sham group were exposed to the cecum only, and sepsis induced ARDS model was reproduced by cecal ligation and puncture (CLP) in the ARDS model group. The general performance was observed at 6, 12, 24 hours after operation. Abdominal aortic blood of rats was collected, and the levels of DMBT1, surfactant-associated protein D (SP-D), vascular endothelial growth factor (VEGF), interleukins (IL-6, IL-10) in serum were determined by enzyme-linked immunosorbent assay (ELISA). The lung tissues were collected, and the lung wet/dry weight (W/D) ratio was determined. The lung tissue pathological changes were observed under light microscope after hematoxylin-eosin (HE) staining, and the lung tissue injury score was evaluated. The expression of DMBT1 protein in lung tissue was determined by Western blotting. The relationship between the serum DMBT1 and SP-D, VEGF, IL-6, IL-10, lung tissue injury score were analyzed by Pearson correlation analysis.Results:Rats in the ARDS model group showed obvious pathological manifestations after operation. The alveolar structure destruction, inflammatory cell infiltration, and alveolar hemorrhage were observed under microscope. Compared with the Sham group, the lung tissue injury score and the lung W/D ratio at 12 hours after operation in the ARDS model group were significantly increased (lung tissue injury score: 3.35±0.13 vs. 1.16±0.07, lung W/D ratio: 5.36±0.44 vs. 4.38±0.35, both P < 0.05), and pulmonary edema was present, which suggested that the ARDS model caused by CLP was successfully reproduced. The results of ELISA and Western blotting showed that the levels of serum DMBT1, SP-D, VEGF and IL-6 in the ARDS model group increased gradually with time, while the level of IL-10 increased first and then decreased. Compared with the Sham group, the levels of DMBT1 in serum and the expressions of DMBT1 protein in lung tissue in the ARDS model group were significantly increased from 6 hours after operation [serum (ng/L) : 231.96±19.17 vs. 187.44±10.19, lung tissue (DMBT1/β-actin): 2.05±0.19 vs. 0.93±0.25, both P < 0.05], and the levels of SP-D, VEGF, IL-6 and IL-10 in serum were significantly increased from 12 hours after operation [SP-D (ng/L): 73.35±8.05 vs. 43.28±5.77, VEGF (ng/L): 89.85±8.47 vs. 43.19±5.11, IL-6 (ng/L): 36.01±2.48 vs. 17.49±1.77, IL-10 (ng/L): 84.55±8.41 vs. 39.83±5.02, all P < 0.05]. Pearson correlation analysis showed that serum DMBT1 was positively correlated with serum SP-D, VEGF, IL-6, IL-10 and lung injury score at 12 hours and 24 hours in the ARDS model group (12 hours: r values were 0.946, 0.942, 0.931, 0.936, 0.748, respectively; 24 hours: r values were 0.892, 0.945, 0.951, 0.918, 0.973, respectively; all P < 0.05). Conclusion:DMBT1 is a novel early biomarker of ARDS by affecting alveolar epithelial cell, alveolar capillary permeability and inflammatory response.

Objective:To study the regulatory effect of Wumen-Yiji powder on 5-hydroxytryptamine (5-HT) signal transduction system in intestine and hypothalamus of diarrhea irritable bowel syndrome (IBS-D) model rats. Methods:Sixty male SD rats were randomly divided into blank group (10 rats) and diarrhea irritable bowel syndrome group (50 rats). The diarrhea irritable bowel syndrome group formed the diarrhea irritable bowel syndrome model after 2 weeks of senna leaf gavage and restraint stress. They were randomly divided into model group, deshute group (1.5 mg/kg), low, medium and high dose group of Wumen-Yiji San (6, 12, 24 g/kg), with 10 rats in each group. After continuous administration for 2 weeks, the contents of 5-HT in serum, colon and hypothalamus were detected by ELISA; HE staining was used to observe the pathological changes of colon in each group. The protein and mRNA levels of tryptophan hydroxylase 1 (TPH-1), serotonin receptor 3 (5-HT3R), serotonin receptor 4 (5-HT4R), serotonin transporter (SERT) in colon and hypothalamus were detected by Western blot and RT-PCR, respectively. Results:Compared with the model group, the pathological morphology of colon in each treatment group was improved. Compared with the model group, the level of 5-HT in serum and colon significantly decreased ( P<0.05), and the level of 5-HT in hypothalamus of rats in the low, medium, high dose group of Wumen-Yiji San significantly increased ( P<0.05). The expression of TPH-1, 5-HT3R and 5-HT4R protein significantly decreased ( P<0.05), and the expression of SERT protein in the medium, high dose group of Wumen-Yiji San significantly increased ( P<0.05). The expression of TPH-1, 5-HT3R and 5-HT4R protein in hypothalamus increased ( P<0.05), and the expression of SERT protein in the high dose group of Wumen-Yiji San significantly decreased ( P<0.05). The mRNA levels of TPH-1 (4.778 ± 0.604, 3.278 ± 0.668, 1.670 ± 0.361 vs. 6.877 ± 0.148), 5-HT3R (3.807 ± 0.463, 2.697 ± 0.455, 1.132 ± 0.136 vs. 6.322 ± 0.778), 5-HT4R (4.521 ± 0.234, 2.801 ± 0.351, 1.331 ± 0.142 vs. 6.741 ± 0.293) in colon tissue of low, medium and high dose groups of Wumen-Yiji San decreased ( P<0.05). The level of 5-HT4R mRNA (0.616 ± 0.208, 0.726 ± 0.226 vs. 0.521 ± 0.062) increased ( P<0.05), and the level of SERT mRNA (1.563 ± 1.023 vs. 2.612 ± 1.035) in medium, high dose group of Wumen-Yiji San decreased ( P<0.05). Conclusion:The result showed that Wumen-Yiji San could regulate the expression of 5-HT signaling system relating proteins and mRNA in the colon and hypothalamus of IBS-D rats within a certain dose range, so as to improve the symptoms of IBS-D.

Objective:To explore the surgical technique and efficacy of pure retroperitoneoscopic extravesical standardized seeable (P.R.E.S.S.) technique for bladder cuff excision (BCE).Methods:Ninety five patients with UTUC from five domestic centers (30 cases from Changzheng Hospital, 21 cases from Peking University First Hospital, 20 cases from Yuhuangding Hospital, 21 cases from Dalian Medical University affiliated No.2 Hospital and 3 cases from General Hospital of Eastern Theater Command)between August 2017 and December 2020 were retrospectively analyzed. There were 57 males and 38 females with a mean age of (67.7±10.0) years and median tumor size of 3.0 cm. All patients underwent pure retroperitoneoscopic radical nephroureterectomy with a single surgical position and four (36 cases) or five (59 cases) trocar layout according to the surgeon’s prefer habit and experience. The demographics of the two groups were the age of [(66.3±11.2)years vs. (68.6±9.1)years], male/female ratio of (25/11 cases vs. 32/27 cases), body mass index of [(25.0± 3.0)kg/m 2 vs. (24.8±3.4)kg/m 2], tumor maximum diameter of [2.8(1.6, 3.5)cm vs. 3.0(2.0, 4.0)cm], left/right side tumor of(19/17 cases vs. 34/25 cases), T 1-2/T 3-4/Tis stage of(25/10/4 cases vs. 49/10/0 cases), and multifocal tumors of(3 cases vs. 2 cases), and the difference was not statistically significant( P>0.05). On the other hand, the differences of hydronephrosis of the operated kidney(13 cases vs. 39 cases, P=0.004), and tumor location (in renal pelvis or calyx or upper/middle/lower ureter being 23/9/4 cases vs. 35/4/20 cases, P=0.005), were statistically significant. The umbilical artery cord was used as anatomical landmark in the process of P. R.E.S.S. bladder cuff excision. The pelvic floor and extraperitoneal space around the ureter were expanded, the bladder wall was opened to form pneumovesicum, and a sufficient bladder cuff resection and exact bladder cuff closure was performed. Perioperative outcomes and follow-up data were analyzed, and the clinical outcomes between the four and five trocars were compared to evaluate the impact of trocar layout on the surgical outcomes. Results:There were 91(95.8%) cases successfully undergoing P. R.E.S.S. BCE technique, with one case converted to open BCE due to bleeding and three cases converted to distal ureter Hem-o-lok clipping because of poor exposure. Median operative time was 180(125, 230)min, and estimated blood loss was 100(50, 100)ml. The overall complication rate was 10.5%(10/95), including 2 cases(2.1%) of intraoperative bleeding, with 1 case treated by transfusion (400 ml), the other case converted to open surgery without transfusion. There were 8 cases of postoperative complications(8.4%), including 7 cases of Clavien-Dindo grade Ⅱ(3 cases of secondary hemorrhage, one case for each of drug allergy, acute renal insufficiency, blood creatinine increased to 490 μmol/L, or lung infection with lymphatic leakage), 1 case of grade Ⅲa(intestinal obstruction treated with insertion of the intestinal obstruction catheter under local anesthesia), and all these patients were discharged smoothly. The difference between the four and five trocars was not statistically significant in the following variables, including the rate of surgical conversion(8.3% vs. 1.7%), estimated intraoperative blood loss(100 ml vs. 60 ml), ratio of intraoperative lymph node dissection (25.0% vs.20.3%), P. R.E.S.S. bladder cuff excision success rate(91.7% vs.98.3%), the incidence of intraoperative and postoperative complications (13.8% vs.8.5%), pT 1-2/pT 3-4/pTis stage(22/11/3 cases vs.37/19/3 cases) and the proportion of recurrence or metastasis(8.3% vs.3.4%)(all P>0.05). However, the differences in the operation time(190 min vs.170 min, P=0.011)and postoperative hospital stay(5 d vs.6 d, P=0.005) were statistically significant. Conclusions:P. R.E.S.S. bladder cuff resection technique is safe and feasible during the procedure of pure retroperitoneoscopic radical nephroureterectomy by a single surgical position and facilitates seeable adequate bladder cuff excision by establishing an enlarged pelvic lateral extraperitoneal space and pneumovesicum. Five-trocar technique is more suitable for patients with lower ureteral tumors but may be associated with a longer postoperative hospital stay compared with the four-trocar technique.

As a complex system, the topology of human's brain network has an important effect on further study of brain's structural and functional mechanism. Graph theory, a kind of sophisticated analytic strategies, is widely used for analyzing complex brain networks effectively and comparing difference of topological structure alteration in normal development and pathological condition. For the purpose of using this analysis methodology efficiently, it is necessary to develop graph-based visualization software. Thus, we developed VisConnectome, which displays analysis results of the brain network friendly and intuitively. It provides an original graphical user interface (GUI) including the tool window, tool bar and innovative double slider filter, brain region bar, runs in any Windows operating system and doesn't rely on any platform such as Matlab. When importing the user-defined script file that initializes the brain network, VisConnectome abstracts the brain network to the ball-and-stick model and render it. VisConnectome allows a series of visual operations, such as identifying nodes and connection, modifying properties of nodes and connection such as color and size with the color palette and size double slider, imaging the brain regions, filtering the brain network according to its size property in a specific domain as simplification and blending with the brain surface as a context of the brain network. Through experiment and analysis, we conclude that VisConnectome is an effective visualization software with high speed and quality, which helps researchers to visualize and compare the structural and functional brain networks flexibly.
Brain ; physiology ; Connectome ; Humans ; Software

Although the development of COVID-19 vaccines has been a remarkable success, the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict. In this study, blood samples were collected from 163 participants who next received two doses of an inactivated COVID-19 vaccine (CoronaVac®) at a 28-day interval. Using TMT-based proteomics, we identified 1,715 serum and 7,342 peripheral blood mononuclear cells (PBMCs) proteins. We proposed two sets of potential biomarkers (seven from serum, five from PBMCs) at baseline using machine learning, and predicted the individual seropositivity 57 days after vaccination (AUC = 0.87). Based on the four PBMC's potential biomarkers, we predicted the antibody persistence until 180 days after vaccination (AUC = 0.79). Our data highlighted characteristic hematological host responses, including altered lymphocyte migration regulation, neutrophil degranulation, and humoral immune response. This study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after COVID-19 vaccination, shedding light on immunization mechanisms and individual booster shot planning.
Humans ; COVID-19 Vaccines ; Leukocytes, Mononuclear ; Proteomics ; COVID-19/prevention & control* ; Vaccination ; Antibodies ; Antibodies, Viral ; Antibodies, Neutralizing