Colorectal inflammatory cancer transformation poses a major risk to patients with colitis. Patients with chronic intestinal inflammation have an approximately 2-3 folds increased risk of developing colorectal cancer (CRC). Unfortunately, there is currently no effective intervention available. Huangqin decoction (HQD), a well-known traditional Chinese medicine (TCM) formula, is frequently clinically prescribed for treating patients with colitis, and its active ingredients have effective antitumour efficacy. Nonetheless, the mechanism of HQD-mediated prevention of colorectal inflammatory cancer transformation remains unclear. A strategy integrating metagenomic, lipidomic, and messenger RNA (mRNA) sequencing analysis was used to investigate the regulatory effects of HQD on the gut microbiome, metabolism and potential mechanisms involved in colorectal inflammatory cancer transformation. Our study revealed that HQD suppressed colorectal inflammatory cancer transformation, which was associated with enhanced intestinal barrier function, decreased the inflammatory response, and regulation of the gut microbiome. Notably, cohousing experiments revealed that the transfer of the gut microbiome from HQD-treated mice largely inhibited the pathological transformation of colitis. Moreover, gut microbiome transfer from HQD-treated mice primarily resulted in the altered regulation of fatty acid metabolism, especially the remodeling of arachidonic acid metabolism, which was associated with the amelioration of pathological transformation. Arachidonic acid metabolism and the key metabolic enzyme arachidonic acid 12-lipoxygenase (ALOX12) were affected by HQD treatment, and no obvious protective effect of HQD was observed in Alox 12 ^-/- mice, which revealed that ALOX12 was a critical mediator of HQD protection against colorectal inflammatory cancer transformation. In summary, multiple omics analyses were applied to produce valuable data and theoretical support for the application of HQD as a promising intervention for the transformation of inflammatory CRC.

Objective:To analyze the expression levels and clinical significance of interferon (IFN)-α/β in the renal cortex and serum of children with lupus nephritis (LN).Methods:A total of 32 children with LN diagnosed in the pediatric nephrology department of the Second Xiangya Hospital of Central South University from December 2017 to September 2020 were selected as the study subjects (LN group). The normal kidney control group consisted of 3 normal kidney transplant volunteers who underwent biopsy of kidney tissue (normal kidney control group), while 14 healthy children who underwent physical examination were collected as the normal control group. According to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), LN patients were divided into mild activity group ( n=8), moderate activity group ( n=9), and severe activity group ( n=15). According to the International Society of Nephrology/Society of Nephrology (ISN/RPS) 2003 LN classification criteria, pathological classification was performed (3 cases in the mild pathological damage group, 8 cases in the moderate pathological damage group, and 11 cases in the severe pathological damage group); Immunohistochemistry was used to detect the expression and distribution of IFN-α/β in glomeruli and renal interstitium; Enzyme linked immunosorbent assay (ELISA) was used to detect the concentration of IFN-α/β in serum samples and analyze its correlation with the pathological classification and disease activity of LN patients. Results:The serum and renal cortex IFN-α/β levels in the LN group were higher than those in the normal control group and normal kidney control group, respectively (all P<0.05). The average level of serum IFN-α/β in the heavy activity group was higher than that in the light and moderate activity groups (all P<0.05). The serum and renal cortex IFN-α/β levels in the severe pathological damage group were significantly higher than those in the mild and moderate pathological damage groups (all P<0.05). Conclusions:IFN-α/β in the renal cortex is closely related to renal injury in LN; Serum IFN-α/β can assist in evaluating the disease activity level of LN to a certain extent.

Background/Aims: To investigate the autoantibody against fumarate hydratase (FH), which is a specific liver failure-associated antigen (LFAA) and determine whether it can be used as a biomarker to evaluate the prognosis of acute-on-chronic liver failure (ACLF). Methods: An immunoproteomic approach was applied to screen specific LFAAs related to differential prognosis of ACLF (n=60). Enzyme-linked immunosorbent assay (ELISA) technology was employed for the validation of the frequency and titer of autoantibodies against FH in ACLF patients with different prognoses (n=82). Moreover, we clarified the expression of autoantibodies against FH in patients with chronic hepatitis B (n=60) and hepatitis B virus-related liver cirrhosis (n=60). The dynamic changes in the titers of autoantibodies against FH were analyzed by sample collection at multiple time points during the clinical course of eight ACLF patients with different prognoses. Results: Ultimately, 15 LFAAs were screened and identified by the immunoproteomic approach.Based on ELISA-based verification, anti-FH/Fumarate hydratase protein autoantibody was chosen to verify its expression in ACLF patients. ACLF patients had a much higher anti-FH autoantibody frequency (76.8%) than patients with liver cirrhosis (10%, p=0.000), patients with chronic hepatitis B (6.7%, p=0.022), and normal humans (0%, p=0.000). More importantly, the frequency and titer of anti-FH protein autoantibodies in the serum of ACLF patients with a good prognosis were much higher than that of patients with a poor prognosis (83.9% vs 61.5%, p=0.019; 1.41±0.85 vs 0.94±0.56, p=0.017, respectively). The titer of anti-FH autoantibodies showed dynamic changes in the clinical course of ACLF. Conclusions The anti-FH autoantibody in serum may be a potential biomarker for predicting the prognosis of ACLF.

Liver disease is one of the most burdensome diseases in the world. Therefore, new technologies are needed to study its pathogenesis in depth; however, because of its complex pathogenesis, there are relatively limited treatment options. Single-cell sequencing (SCS), as an emerging sequencing method, reflects the heterogeneity between cells by sequencing the genome, transcriptome, and epigenome of a single cell, thereby revealing the complex mechanisms of disease occurrence and development. The application of SCS in the study of liver diseases will enrich our understanding of the pathogenesis of liver diseases and provide a new direction for exploring the diagnosis and treatment. This article mainly reviews the research progress of SCS technology in liver diseases.

OBJECTIVES: To determine the potential molecular mechanisms underlying the therapeutic effect of curcumin on hepatocellular carcinoma (HCC) by network pharmacology and experimental in vitro validation. METHODS: The predictive targets of curcumin or HCC were collected from several databases. the identified overlapping targets were crossed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform. Two of the candidate pathways were selected to conduct an experimental verification. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay was used to determine the effect of curcumin on the viability of HepG2 and LO2 cells. The apoptosis and autophagy of HepG2 cells were respectively detected by flow cytometry and transmission electron microscopy. Besides, western blot and real-time polymerase chain reaction (PCR) were employed to verify the p53 apoptotic pathway and adenosine 5'-monophosphate (AMP)‍-activated protein kinase (AMPK) autophagy pathway. HepG2 cells were pretreated with pifithrin-‍α (PFT-‍α) and GSK690693 for further investigation. RESULTS: The 167 pathways analyzed by KEGG included apoptosis, autophagy, p53, and AMPK pathways. The GO enrichment analysis demonstrated that curcumin was involved in cellular response to drug, regulation of apoptotic pathway, and so on. The in vitro experiments also confirmed that curcumin can inhibit the growth of HepG2 cells by promoting the apoptosis of p53 pathway and autophagy through the AMPK pathway. Furthermore, the protein and messenger RNA (mRNA) of the two pathways were downregulated in the inhibitor-pretreated group compared with the experimental group. The damage-regulated autophagy modulator (DRAM) in the PFT-‍α-pretreated group was downregulated, and p62 in the GSK690693-pretreated group was upregulated. CONCLUSIONS Curcumin can treat HCC through the p53 apoptotic pathway and the AMPK/Unc-51-like kinase 1 (ULK1) autophagy pathway, in which the mutual transformation of autophagy and apoptosis may occur through DRAM and p62.
AMP-Activated Protein Kinases/pharmacology* ; Apoptosis ; Carcinoma, Hepatocellular/pathology* ; Curcumin/pharmacology* ; Humans ; Liver Neoplasms/pathology* ; Network Pharmacology ; Tumor Suppressor Protein p53/metabolism*

Objective:To study the clinical application of ultrasound-guided puncture and catheter tip positioning in peripherally inserted central catheter (PICC) among very/extremely low birth weight infants (VLBWI/ELBWI).Method:From January 2019 to August 2020, VLBWI/ELBWI admitted to NICU of our hospital and received PICC were prospectively enrolled in the study. Based on the last digit of medical record number was odd or even, the infants were assigned into ultrasound group and X-ray group. In the ultrasound group, puncture and catheter tip positioning were performed at bedside guided by ultrasound, while in the X-ray group, these procedures were performed empirically. The differences of catheterization procedure duration, first-time success rate, the visibility of catheter tip, primary dislocation rate, secondary dislocation rate and complication rate were compared between the two groups using SPSS 25.0.Result:A total of 118 premature infants were enrolled, including 57 cases in ultrasound group (50 cases VLBWI and 7 cases ELBWI) and 61 cases in X-ray group (54 cases VLBWI and 7 cases ELBWI). The catheterization procedure duration [(23.2±7.1) min vs. (34.1±7.5) min], first-time success rate (93.0% vs. 65.6%), the visibility of catheter tip (96.5% vs. 83.6%), primary dislocation rate (7.0% vs. 24.6%) and complication rate (7.0% vs. 21.3%) in ultrasound group were all better than X-ray group ( P<0.05). For ELBWI, the above five indexes in the ultrasound group were better than the X-ray subgroup ( P<0.05). For VLBWI, only the catheterization procedure duration and first-time success rate were better in the ultrasound group than the X-ray group ( P<0.05). Conclusion:Ultrasound-guided PICC catheterization in VLBWI/ELBWI is convenient and accurate, which can improve success rate, reduce radiation exposure and repeated catheterization injury. Timely tracking and adjustment of the catheter under ultrasound can reduce complications after catheterization. This technique is worth popularizing among VLBWI/ELBWI.

Objective To comparatively analyze the safety and efficacy of direct mechanical thrombectomy and bridging therapy for patients with acute anterior circulation large-artery occlusive stroke.Methods A total of 116 patients with acute anterior circulation large-artery occlusive stroke,admitted to our hospitals from October 2015 to March 2018,were chosen in our study;their clinical data were analyzed retrospectively.Among them,63 patients accepted direct mechanical thrombectomy and 53 accepted bridging therapy.The preoperative baseline data and the diagnoses and treatments of the two groups were analyzed;the degrees of modified thrombolysis in cerebral infarction (mTICI),incidences of hemorrhage transformation and symptomatic intracranial hemorrhage,and modified Rankin scale (mRS) scores and mortality rate 90 d after operation were compared between the two groups.Results The preoperative Alberta stroke program early CT scale (ASPECTS) and Glasgow Coma Scale (GCS) scores of the direct mechanical thrombectomy group were significantly lower than those of the bridge therapy group (P＜0.05),and the time from onset to admission was significantly longer than that of the bridging therapy group (P＜0.05).The incidence of postoperative hemorrhage transformation in the direct mechanical thrombectomy group was significantly higher than that in the bridging therapy group (34.9％ vs.17.0％,P＜0.05),but there were no significant differences in the effective recanalization rate (69.8％ vs.79.3％),intracranial symptomatic hemorrhage rate (15.9％ vs.7.6％),favorable outcome rate (28.6％ vs.35.9％) and mortality (22.2％ vs.17.0％) between the two groups (P＞0.05).Conclusion The clinical efficacy and safety of direct mechanical thrombectomy and bridging therapy for patients with acute anterior circulation large-artery occlusive stroke are similar.

Objective To evaluate efficacy and safety of fluoxetine in comparison with placebo in children and adolescents with depression. Methods Randomized controlled trials (RCTs) on fluoxetine were searched in CBM,Wangfang, VIP,CNKI,PubMed,EMbase,Ovide and Cochrane Library from inception to October 2016 by computer.The pooled mean difference and relative risk were assessed by Meta analysis with RevMan 5.0 software. Results A total of 8 RCTs were included for the final analysis.Curative effect analysis showed:in Children's Global Assessment Scale [MD= 3.91,95％CI(1.66,6.16),P= 0.0007] and Children's Depression Inventory [MD = -1.98,95％CI(-3.40,-0.57),P = 0.006],fluoxetine exerted a good effect in treating children's depression.Fluoxetine was equivalent to placebo in safety. Conclusion This study supports the conclusion that the benefits of fluoxetine in treating children and adolescents with depression are greater than the potential risk.

Objective To explore the difference of gene expression profiling between normal basilar arteries and basilar arteries of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) in rabbits. Methods cDNA chip of normal basilar arteries and basilar arteries of CVS after SAH in rabbits were downloaded from GEO database. The chip was analyzed and screened by Bioconductor software, and function enrichment and pathway analysis of the differentially expressed genes were analyzed by Cytoscape software. Then 6 adult male Japanese rabbits were used, and randomly divided into normal control group (n=3) and SAH model group (n=3). Rabbit SAH models were established by cisterna secondary-blood-injection method. RNA data of normal basilar artery specimens on the 0 day and basilar artery specimens after SAH on the 5-day were used to validate the parts of differentially expressed genes by qRT-PCR. Results A total of 4356 differentially expressed genes were found in normal basilar arteries and basilar arteries of CVS after SAH in rabbits. Among them, 920 genes were considered to be significant with P-value<0.05, such as GRIK1, MYH13, ZNF45, SAA3, RLN1, MSR1 and others. Function enrichment analysis indicated that the differentially expressed genes were involved in regulation of Ca2+transmembrane transporter activity, negative regulation of ion transmembrane transport, regulation of potassium ion transport, positive regulation of JAK-STAT signaling cascades and other biological processes. Pathway analysis showed that calcium signaling pathway, cGMP-PKG signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway and other signaling pathways maybe related with the differentially expressed genes. qRT-PCR verification showed that the expression of MSR1 in SAH model group was consistent with that of the chip result. Conclusion The gene expressions of basilar arteries of CVS after SAH in rabbits are significantly different, and MSR1 gene can be used as a potential target for studying the pathological mechanism of CVS.

Objective To evaluate the efifcacy and inlfuencing factors of 3%hypertonic saline (HS) inhalation in treatment of bronchiolitis. Methods Clinical data together with the detection of 16 types of respiratory tract virus from hospitalized pediatric patients with primary diagnosis of bronchiolitis from June 2009 to December 2012 were retrospectively analyzed. The endpoint indicators for evaluation on the efifcacy of nebulized 3%HS inhalation were the percent decrease of clinical severity (CS) score after 2 days' treatment and the hospitalization time. Factors affecting efifcacy were further explored. Results The CS score in nebulized 3%HS treated group decreased in average of 42.86%(11.11%-66.67%), signiifcantly higher than that (26.79%, 0.00%-50.00%) in the untreated group (P=0.006). No difference of between the two groups (P=0.26). Multiple linear regression analysis showed that nebulized 3%HS inhalation has better efifcacy on the patients older than 3 months having breastfeeding, respiratory synthetic syncytial virus (RSV) infection and extensive wheezing sound auscultation of the lungs. The multiple linear regression analysis model was statistically signiifcant (R2=0.58, P<0.001). Conclusions After 2 days' treatment with 3%hypertonic saline inhalation, the CS score of bronchiolitis patients was decreased. The treatment can be recommended in hospitalized patient older than 3 months with breastfeeding, RSV infection, and extensive wheezing sound auscultation of the lungs.