Schizophrenia is a severe psychiatric disorder with an unclear etiology and various clinical manifestations. The diagnosis and consequent treatment of schizophrenia mainly rely on clinical symptoms. Multiple risk sites associated with schizophrenia have been identified, yet objective indicators have not been found to facilitate clinical diagnosis and treatment of schizophrenia. The development of omics technology provides different perspectives on the etiology of schizophrenia and make the early identification, diagnosis and treatment of the disorder possible. This article summarizes the prevalence of schizophrenia, reviews the research results and shortcomings of transcriptomics and proteomics, as well as the latest achievements and prospects of multi-omics, aiming to reveal the use of omics in SZ, provide more comprehensive biological evidence to reveal the complex pathogenesis of schizophrenia and provide a theoretical basis for the early identification, accurate diagnosis, disease progression control, and prognosis improvement of schizophrenia.
Humans ; Proteomics/methods* ; Transcriptome ; Schizophrenia/genetics*

Schizophrenia is a severe psychiatric disorder with an unclear etiology and various clinical manifestations. The diagnosis and consequent treatment of schizophrenia mainly rely on clinical symptoms. Multiple risk sites associated with schizophrenia have been identified, yet objective indicators have not been found to facilitate clinical diagnosis and treatment of schizophrenia. The development of omics technology provides different perspectives on the etiology of schizophrenia and make the early identification, diagnosis and treatment of the disorder possible. This article summarizes the prevalence of schizophrenia, reviews the research results and shortcomings of transcriptomics and proteomics, as well as the latest achievements and prospects of multi-omics, aiming to reveal the use of omics in SZ, provide more comprehensive biological evidence to reveal the complex pathogenesis of schizophrenia and provide a theoretical basis for the early identification, accurate diagnosis, disease progression control, and prognosis improvement of schizophrenia.
Humans ; Proteomics/methods* ; Transcriptome ; Schizophrenia/genetics*

Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; China/epidemiology* ; Heart Valve Prosthesis Implantation ; Humans ; Severity of Illness Index ; Treatment Outcome

OBJECTIVE Baicalin is a major flavonoid component of Scutellaria baicalensis, and has been used in the treatment of liver diseases for many years. However, the role of baicalin in estrogen-induced cholestasis (EIC) remains to be elucidated. This present study explored the protective effect of baicalin against estrogen-induced liver injury and further elucidated the mechanisms involved both in vivo and in vitro. METHODS We conducted a series of experiments using 17α-ethinylestradiol (EE) induced cholestatic rats and cultured HepG2 cells. Serum, bile, and liver samples were collected for biochemical and histological analyses. Bile acid composition in liver was analyzed by LC-MS/MS. The mechanisms underlying the hepatoprotective of baicalin were investigated by RT-PCR, Western blotting analyses and immunohistochemistry. RESULTS Baicalin showed obvious hepatoprotective effects in EIC rats by reducing serum bio?markers and increasing the bile flow rate, as well as by alleviating liver histology and restoring the abnormal composition of hepatic bile acids (BAs). In addition, baicalin protected against EE induced liver injury by up-regulation of the expres?sion of hepatic efflux transporters and down-regulation of hepatic uptake transporters. Furthermore, baicalin increased the expression of hepatic BA synthase (CYP27A1) and metabolic enzymes (Bal, Baat and Sult2a1) in EIC rats. We showed that baicalin significantly inhibited hepatic inflammatory responses in EIC rats through reducing elevated levels of TNF-α, IL-1β, IL-6 and NF-κB. Finally, we confirmed that baicalin maintains BA homeostasis and alleviates inflamma?tion through Sirt1/HNF-1α/FXR signaling pathway. CONCLUSION Baicalin protects against estrogen-induced cholestatic liver injury, and the underlying mechanism involved is related to activation of the Sirt1/HNF-1α/FXR signaling pathway.

Intestinal organoids, also named "mini-guts", reconstitute sophisticated three-dimensional architecture recapitulating diversified intestinal epithelial cell types and physiology, which is driven by the proliferative and self-assembling characteristics of crypt stem cells. The initiation of organoids study relies on the identification of Lgr5+ crypt stem cells from different intestinal segments and the key role of EGF, Wnt, BMP/TGF-β, Notch signal pathways within the microenvironment during the cultivation process. Besides constituting polarized crypt-villus structures, these "mini-guts" exhibit various effective functions of intestinal epithelium. Since 2009 when the culture system of small intestinal organoids was established by Sato et al, intestinal organoids excel conventional intestinal models depending on genetical mutation in multiple aspects and thus have become the hotspot among the research on intestinal diseases. Combined with genomics, material science and engineering, "mini-guts" have been widely applied to the research on intestinal development, intestinal transport physiology, epithelial barrier, pathogen-host interaction and the study on cystic fibrosis, infectious diarrhea, ulcerative colitis, Crohn's disease, intestinal cancer, etc. In this review, we summarize the new insights introduced by organoid into the research on intestinal diseases, and related research advances and applications.
Humans ; Intestinal Mucosa ; Intestinal Neoplasms ; Intestines ; Organoids ; Stem Cells ; Tumor Microenvironment

: Objective: To investigate the efficacy of fistula stent made by 3D printing technique in the treatment of enteroatmospheric fistula. Methods: A descriptive case series study was carried out. INCLUSION CRITERIA: (1) patients with open abdomen; (2) patients with enteroatmospheric fistula. EXCLUSION CRITERIA: (1) patient with two or more fistulas; (2) distal obstruction; (3) bowel stenosis over 50%. According to above criteria, 17 EAF patients admitted to the General Surgery Department of Jinling Hospital from June 2019 to January 2020 were retrospectively included in study. Based on the intestinal radiography, CT reconstruction and finger exploration, the size of fistula, the diameter of the intestinal tube and the angle of the intestinal lumen around the fistula were assessed. The 3D printing fistula stent was designed and established based on estimated data, and then placed through the fistula. OUTCOME MEASUREMENTS (1) success rate of stent implantation; (2) outflow of intestinal contents after implantation; (3) tolerated exercise time; (4) receiving definite operation time for intestinal fistula; (5) time to recovery of enteral nutrition. The t-test was used to compare the outflow amount of intestinal content before and after the stent implantation and the tolerated exercise time. The changes of the outflow amount of intestinal content and tolerated exercise time were analyzed by repeated measurement ANOVA. Results: Seventeen EAF patients with open abdomen included 13 males and 4 females. All the patients successfully received intestinal fistula stent implantation. Gastrointestinal angiography 2 days after implantation showed that the digestive tract was unobstructed, and the stent was successfully kept in place until definite surgery. No stent implantation-related adverse reactions were found in patients undergoing definite intestinal fistula surgery. The average outflow amount of intestinal fluid within 7 days after implantation decreased from (702.7±198.9) ml/d to on the first day after implantation (45.8±22.4) ml/d on the 7th day(F=10.380, P<0.001). The ambulatory time and exercise time of patients continued to increase after stent implantation. The average tolerated exercise time within 14 days after stent implantation increased from (9.1±3.8) min/d to (106.9±21.8) min/d (F=41.727, P<0.001). Within 120 days after stent implantation, 15 patients successfully underwent definite surgery for intestinal fistula and reconstruction of abdominal wall. Patients needed a median (IQR) of 3 (2, 5) days to recover enteral nutrition. The average time from stent placement to surgery was (87.2±17.6) days. Two patients died of severe abdominal infection with multiple organ failure. Conclusion: 3D printing fistula stent can significantly and the outflow of intestinal contents and the difficulty of nursing, and help to restore enteral nutrition and rehabilitation exercise as soon as possible in EAF patients with open abdomen.
Abdominal Wall ; Female ; Humans ; Intestinal Fistula/surgery* ; Male ; Printing, Three-Dimensional ; Retrospective Studies ; Stents ; Treatment Outcome

Forskolin is a complex labdane plant diterpenoid, which has been used in the treatment of a variety of diseases based on its activity as an activator of adenosine monophosphate(cAMP) cyclase. Natural forskolin exists only in the cork layer of the root of Coleus forskohlii. Due to the complexity of the extraction and chemical synthesis processes, the yield and purity of forskolin cannot meet commercial requirements. In recent years, with the rapid development of synthetic biology and the analysis and interpretation of many diterpene biosynthetic pathways, a new approach has been provided for the green production of forskolin. In this paper, the structure, activity, biosynthetic pathway and the heterologous biosynthesis of forskolin were reviewed. The problems and solutions in the heterologous biosynthesis of forskolin were also discussed and summarized, which will provide references for the construction of high-yielding forskolin engineering strains.
Biosynthetic Pathways ; Colforsin

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01). CONCLUSIONS Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.
Anti-Bacterial Agents ; Birth Weight ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; Surveys and Questionnaires

Background::The use of microRNAs in the therapy of kidney disease is hampered by the difficulties in their effective delivery. Microvesicles (MVs) are known as natural carriers of small RNAs. Our prior research has demonstrated that MVs isolated from mesenchymal stem cells (MSCs) are capable of attenuating kidney injuries induced by unilateral ureteral obstruction and 5/6 sub-total nephrectomy in mice. The present study aimed to evaluate the effects of miR-34a-5p (miR-34a)-modified MSC-MVs on transforming growth factor (TGF)-β1-induced fibrosis and apoptosis in vitro. Methods::Bone marrow MSCs were modified by lentiviruses over-expressing miR-34a, from which MVs were collected for the treatment of human Kidney-2 (HK-2) renal tubular cells exposed to TGF-β1 (6 ng/mL). The survival of HK-2 cells was determined using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and Annexin V-Light 650/propidium iodide (PI) assays. The expression levels of epithelial markers (tight junction protein 1 [TJP1] and E-cadherin) and mesenchymal markers (smooth muscle actin alpha (α-SMA) and fibronectin) in HK-2 cells were measured using Western blot analysis and an immunofluorescence assay. In addition, changes in Notch-1/Jagged-1 signaling were analyzed using Western blotting. Data were analyzed using a Student’s t test or one-way analysis of variance. Results::MiR-34a expression increased three-fold in MVs generated by miR-34a-modified MSCs compared with that expressed in control MVs ( P < 0.01, t= 16.55). In HK-2 cells, TJP1 and E-cadherin levels decreased to 31% and 37% after treatment with TGF-β1, respectively, and were restored to 62% and 70% by miR-34a-enriched MSC-MVs, respectively. The expression of α-SMA and fibronectin increased by 3.9- and 5.0-fold following TGF-β1 treatment, and decreased to 2.0- and 1.7-fold after treatment of HK-2 cells with miR-34a-enriched MSC-MVs. The effects of miR-34a-enriched MSC-MVs on epithelial-mesenchymal transition (EMT) markers were stronger than control MSC-MVs. The effects of miR-34a-enriched MSC-MVs on these EMT markers were stronger than control MSC-MVs. Notch-1 receptor and Jagged-1 ligand, two major molecules of Notch signaling pathway, are predicted targets of miR-34a. It was further observed that elevation of Notch-1 and Jagged-1 induced by TGF-β1 was inhibited by miR-34a-enriched MSC-MVs. In addition, TGF-β1 exposure also induced apoptosis in HK-2 cells. Although miR-34a-mofidied MSC-MVs were able to inhibit TGF-β1-triggered apoptosis in HK-2 cells, the effects were less significant than control MSC-MVs (control:TGF-β1 :miR-nc-MV:miR-34a-MV = 1.3:0.6:1.1:0.9 for MTT assay, 1.8%:23.3%:9.4%:17.4% for apoptosis assay). This phenomenon may be the result of the pro-apoptotic effects of miR-34a. Conclusions::The present study demonstrated that miR-34a-over-expressing MSC-MVs inhibit EMT induced by pro-fibrotic TGF-β1 in renal tubular epithelial cells, possibly through inhibition of the Jagged-1/Notch-1 pathway. Genetic modification of MSC-MVs with an anti-fibrotic molecule may represent a novel strategy for the treatment of renal injuries.