Prediction model for hepatitis B e antigen seroconversion in chronic hepatitis B with peginterferon-alfa treated based on a responseguided therapy strategy

BACKGROUND Models for predicting hepatitis B e antigen(HBeAg)seroconversion in patients with HBeAg-positive chronic hepatitis B(CHB)after nucleos(t)ide analog treatment are rare.AIM To establish a simple scoring model based on a response-guided therapy(RGT)strategy for predicting HBeAg seroconversion and hepatitis B surface antigen(HBsAg)clearance.METHODS In this study,75 previously treated patients with HBeAg-positive CHB underwent a 52-week peginterferon-alfa(PEG-IFNα)treatment and a 24-wk follow-up.Logistic regression analysis was used to assess parameters at baseline,week 12,and week 24 to predict HBeAg seroconversion at 24 wk post-treatment.The two best predictors at each time point were used to establish a prediction model for PEG-IFNαtherapy efficacy.Parameters at each time point that met the corresponding optimal cutoff thresholds were scored as 1 or 0.RESULTS The two most meaningful predictors were HBsAg≤1000 IU/mL and HBeAg≤3 S/CO at baseline,HBsAg≤600 IU/mL and HBeAg≤3 S/CO at week 12,and HBsAg≤300 IU/mL and HBeAg≤2 S/CO at week 24.With a total score of 0 vs 2 at baseline,week 12,and week 24,the response rates were 23.8%,15.2%,and 11.1%vs 81.8%,80.0%,and 82.4%,respectively,and the HBsAg clearance rates were 2.4%,3.0%,and 0.0%,vs 54.5%,40.0%,and 41.2%,respectively.CONCLUSION We successfully established a predictive model and diagnosis-treatment process using the RGT strategy to predict HBeAg and HBsAg seroconversion in patients with HBeAg-positive CHB undergoing PEG-IFNαtherapy.

大黄贴敷联合复方聚乙二醇电解质散口服对便秘患者肠道准备给药时机的影响

目的探讨大黄贴敷神阙穴和天枢穴联合口服复方聚乙二醇电解质散(PGEP)在便秘患者肠道准备中的给药时机。方法选择行结肠镜检查的便秘患者300例,分3组,各100例。A组检查前1天晚上9点,行中药贴敷神阙穴和天枢穴,检查当天早上5~7点服完PGEP 139.12 g(2 000 ml);B组检查前1天晚上9点行中药贴敷神阙穴和天枢,检查当天上午10~12点服完相同剂量的PGEP;C组检查当天早上5点行中药贴敷神阙穴和天枢穴,早上5~7点服完相同剂量的PGEP。服药后4 h行结肠镜检查。应用Boston肠道准备量表(BBPS)评分,并对肠腔内气泡进行评分,比较3组患者肠道准备有效性、耐受性及安全性。结果 A组的肠镜检查时间(7.25±0.60)min明显短于B组(9.10±0.80)min和C组(10.50±0.55)min;A组的BBPS评分(8.50±0.35)分明显高于B组(7.35±1.25)分和C组(6.65±1.30)分;A组的肠腔内气泡评分(0.25±0.15)分明显低于B组(0.75±0.65)分和C组(0.55±0.50)分;A组肠道准备接受率、再次肠道准备接受率(96.00%、93.00%)明显高于B组(85.00%、70.00%)和C组(90.00%、88.00%);A组的总体不良反应评分(1.45±0.04)分明显低于B组(1.75±0.55)分和C组(1.60±0.25)分。差异均有统计学意义(P<0.05)。结论检查前1天晚上9点大黄穴位贴敷联合检查当天早上5~7点口服PGEP对便秘患者行结肠镜检查肠道准备效果好。

问题导向学习法在临床医学科研型研究生教育中的应用

问题导向学习法(problem-based learning,PBL)已成为目前西方国家医学教育的主流模式之一,其在培养学生分析问题、解决问题以及自我学习能力等方面有极大促进作用。本文结合自身实践,就PBL在临床医学科研型研究生教育过程中的应用及相关问题进行论述。

Models for predicting hepatitis B e antigen seroconversion in response to interferon-α in chronic hepatitis B patients

AIM:To develop models to predict hepatitis B e antigen(HBe Ag)seroconversion in response to interferon(IFN)-αtreatment in chronic hepatitis B patients.METHODS:We enrolled 147 treatment-nave HBe Agpositive chronic hepatitis B patients in China and analyzed variables after initiating IFN-α1b treatment.Patients were tested for serum alanine aminotransferase(ALT),hepatitis B virus-DNA,hepatitis B surface antigen(HBs Ag),antibody to hepatitis B surface antigen,HBe Ag,antibody to hepatitis B e antigen(anti-HBe),and antibody to hepatitis B core antigen(anti-HBc)at baseline and 12 wk,24 wk,and 52 wk after initiating treatment.We performed univariate analysis to identify response predictors among the variables.Multivariate models to predict treatment response were constructed at baseline,12 wk,and 24 wk.RESULTS:At baseline,the 3 factors correlating most with HBe Ag seroconversion were serum ALT level>4×the upper limit of normal(ULN),HBe Ag≤500 S/CO,and anti-HBc>11.4 S/CO.At 12 wk,the 3 factors most associated with HBe Ag seroconversion were HBe Ag level≤250 S/CO,decline in HBe Ag>1 log10 S/CO,and anti-HBc>11.8 S/CO.At 24 wk,the 3 factors most associated with HBe Ag seroconversion were HBe Ag level≤5 S/CO,anti-HBc>11.4 S/CO,and decline in HBe Ag>2 log10 S/CO.Each variable was assigned a score of1,a score of 0 was given if patients did not have any of the 3 variables.The 3 factors most strongly correlating with HBe Ag seroconversion at each time point were used to build models to predict the outcome after IFN-αtreatment.When the score was 3,the response rates at the 3 time points were 57.7%,83.3%,and 84.0%,respectively.When the score was 0,the response rates were 2.9%,0.0%,and 2.1%,respectively.CONCLUSION:Models with good negative and positive predictive values were developed to calculate the probability of response to IFN-αtherapy.

MiR-21 Suppresses Anoikis through Targeting PDCD4 and PTEN in Human Esophageal Adenocarcinoma

Anoikis is a form of apoptosis induced upon cell detachment from extracellular matrix. It has been determined that acquisition of resistance to anoikis is a critical step for tumor cell metastasis. MiR-21, the most prominent oncomiR, plays an important role in tumor progression. In this study, we revealed that up-regulation of miR-21 in human esophageal adenocarcinoma （EA） is associated with lymph node metastasis and poor survival rate. Because of the established anti-apoptosis effect of miR-21, it is tempting to speculate that miR-21 might contribute to tumor metastasis by regulating anoikis, qRT-PCR analysis demonstrated that miR-21 expression in OE33/AR cells （subpopulation of human EA OE33 cells that acquired resistance to anoikis） was significantly increased. Also, transfection of miR-21 mimics provided OE33 cells resisting to anoikis. By luciferase assays, we verified that PDCD4 and PTEN were the functional targets of miR-21. In mouse model, via tail vein injection experiment, we showed that the metastasis formation of OE33 cells in vivo could be mediated by changing the miR-21 expression pattern. Taken together, our findings suggested that miR-21 was involved in the regulation of anoikis in human EA cells. Targeting miR-21 may provide a novel strategy to prevent metastasis.

Dependence of interferogram phase on incident wavenumber and phase stability of Doppler asymmetric spatial heterodyne spectroscopy

Instrument drifts introduce additional phase errors into atmospheric wind measurement of Doppler asymmetric spatial heterodyne spectroscopy (DASH). Aiming at the phase sensitivity of DASH to instrument drifts, in this paper we calculate the optical path difference (OPD) and present an accurate formula of DASH interferogram. By controlling variables in computational ray-tracing simulations and laboratory experiments, it is indicated that initial phase is directly determined by incident wavenumber, OPD offset and field of view (FOV). Accordingly, it is indicated that retrieved phase of DASH is sensitive to slight structural change caused by instrument drift, which provides the proof of necessary-to-track and -correct phase errors from instrument drifts.

Postoperative survival analysis and prognostic nomogram model for patients with portal hypertension

AIM To analyse the postoperative survival of patients with portal hypertension and determine the factors that influence survival and construct nomograms.METHODS We retrospectively followed 1045 patients who underwent splenectomy plus pericardial devascularisation(SPD) between January 2002 and December 2017. Two SPD types are used in our department: splenectomy plus simplified pericardial devascularisation(SSPD) and splenectomy plus traditional pericardial devascularisation(STPD). The Kaplan-Meier method and Cox regression analysis were used to evaluate the prognostic effects of multiple parameters on overall survival(OS), diseasespecific survival(DSS) and bleeding-free survival(BFS). Significant prognostic factors were combined to build nomograms to predict the survival rate of individual patients.RESULTS Five hundred and fifty-seven(53.30%) patients weresuccessfully followed with 192 in the SSPD group and 365 in the STPD group; 93(16.70%) patients died, of whom 42(7.54%) died due to bleeding. Postoperative bleeding was observed in 84(15.10%) patients. The 5-and 10-year OS, DSS and BFS rates in the group of patients who underwent SSPD were not significantly different from those in patients who underwent STPD. Independent prognostic factors for OS were age, operative time, alanine transaminase level and albumin-bilirubin score. Independent prognostic factors for BFS were male sex, age, intraoperative blood loss and time to first flatus. Independent prognostic factors for DSS were the Comprehensive Complication Index and age. These characteristics were used to establish nomograms, which showed good accuracy in predicting 1-, 3-and 5-year OS and BFS.CONCLUSION SSPD achieves or surpasses the long-term survival effect of traditional pericardial devascularisation and is worthy of clinical promotion and application. Nomograms are effective at predicting prognosis.

Global trends and hotspots of treatment for nonalcoholic fatty liver disease:A bibliometric and visualization analysis(2010-2023)

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is chronic,with its progression leading to liver fibrosis and end-stage cirrhosis.Although NAFLD is increasingly common,no treatment guideline has been established.Many mechanistic studies and drug trials have been conducted for new drug development to treat NAFLD.An up-to-date overview on the knowledge structure of NAFLD through bibliometrics,focusing on research hotspots,is necessary to reveal the rational and timely directions of development in this field.AIM To research the latest literature and determine the current trends in treatment for NAFLD.METHODS Publications related to treatment for NAFLD were searched on the Web of Science Core Collection database,from 2010 to 2023.VOSviewers,CiteSpace,and R package“bibliometrix”were used to conduct this bibliometric analysis.The key information was extracted,and the results of the cluster analysis were based on network data for generating and investigating maps for country,institution,journal,and author.Historiography analysis,bursts and cluster analysis,cooccurrence analysis,and trend topic revealed the knowledge structure and research hotspots in this field.GraphPad Prism 9.5.1.733 and Microsoft Office Excel 2019 were used for data analysis and visualization.RESULTS In total,10829 articles from 120 countries(led by China and the United States)and 8785 institutions were included.The number of publications related to treatment for NAFLD increased annually.While China produced the most publications,the United States was the most cited country,and the United Kingdom collaborated the most from an international standpoint.The University of California-San Diego,Shanghai Jiao Tong University,and Shanghai University of Traditional Chinese Medicine produced the most publications of all the research institutions.The International Journal of Molecular Sciences was the most frequent journal out of the 1523 total journals,and Hepatology was the most cited and co-cited journal.Sanyal AJ was the most cited author,the most co-cited author was Younossi ZM,and the most influential author was Loomba R.The most studied topics included the epidemiology and mechanism of NAFLD,the development of accurate diagnosis,the precise management of patients with NAFLD,and the associated metabolic comorbidities.The major cluster topics were“emerging drug,”“glucagon-like peptide-1 receptor agonist,”“metabolic dysfunction-associated fatty liver disease,”“gut microbiota,”and“glucose metabolism.”CONCLUSION The bibliometric study identified recent research frontiers and hot directions,which can provide a valuable reference for scholars researching treatments for NAFLD.

Sequential vs simultaneous revascularization in patients undergoing liver transplantation:A meta-analysis

AIM: We undertook this meta-analysis to investigate the relationship between revascularization and outcomes after liver transplantation.METHODS: A literature search was performed using MeSH and key words. The quality of the included studies was assessed using the Jadad Score and the NewcastleOttawa Scale. Heterogeneity was evaluated by the χ 2and I 2 tests. The risk of publication bias was assessed using a funnel plot and Egger's test, and the risk of bias was assessed using a domain-based assessment tool.A sensitivity analysis was conducted by reanalyzing the data using different statistical approaches.RESULTS: Six studies with a total of 467 patients were included. Ischemic-type biliary lesions were significantly reduced in the simultaneous revascularization group compared with the sequential revascularization group(OR = 4.97, 95%CI: 2.45-10.07; P < 0.00001),and intensive care unit(ICU) days were decreased(MD = 2.00, 95%CI: 0.55-3.45; P = 0.007) in the simultaneous revascularization group. Although warm ischemia time was prolonged in simultaneous revascularization group(MD =-25.84, 95%CI:-29.28-22.40; P < 0.00001), there were no significant differences in other outcomes between sequential and simultaneous revascularization groups. Assessment of the risk of bias showed that the methods of random sequence generation and blinding might have been a source of bias. The sensitivity analysis strengthened the reliability of the results of this meta-analysis.CONCLUSION: The results of this study indicate that simultaneous revascularization in liver transplantation may reduce the incidence of ischemic-type biliary lesions and length of stay of patients in the ICU.

Comparison of simplified and traditional pericardial devascularisation combined with splenectomy for the treatment of portal hypertension

AIM To compare the clinical outcomes of patients with portal hypertension(PH) who underwent treatment with splenectomy plus simplified pericardial devascularisation(SSPD) or splenectomy plus traditional pericardial devascularisation(STPD).METHODS We conducted a single-centre retrospective study of 1045 PH patients treated with either SSPD(S Group, 357 patients) or STPD(T Group, 688 patients) between January 2002 and February 2017. In all, 37 clinical indicators were compared to evaluate the efficacy of SSPD.RESULTS Perioperative indicators in the S Group were significantly better than those in the T Group(P < 0.05). In both groups, the postoperative long-term portal vein diameter and Model for End-Stage Liver Disease score were significantly lower than those in the preoperative and postoperative short-term groups(P< 0.05). The incidence of complications in the S Group was significantly lower than that in the T Group(P < 0.05). Compared to the T Group, postoperative shortterm WBC(white blood cell) and platelet counts were significantly lower and the short-term Hb(haemoglobin) level was significantly higher in the S Group(P < 0.05). In the S Group, postoperative long-term total bilirubin, direct bilirubin, alanine transaminase, and aspartate transaminase and postoperative serum creatinine and cystatin C levels were significantly lower than those in the T Group(P < 0.05), and postoperative albumin was significantly higher than that in the T Group(P < 0.05).CONCLUSION Compared to STPD, SSPD is a simple and easy procedure resulting in less tissue damage. Patients recovered smoothly and steadily with fewer complications. Short-term liver and kidney function damage was less severe, and long-term liver function recovery was better. Therefore, SSPD is worthy of clinical promotion and application for the treatment of PH.

Hepatic artery bridging lessens temporary ischemic injury to bile canaliculi

AIM: To study whether transfer of blood between the right gastroepiploic artery and gastroduodenal artery could lessens the damage to bile canaliculi.METHODS: Forty male Bama miniature pigs were divided into four groups as follows: a control group, two hepatic artery ischemia groups(1 h and 2 h), and a hepatic artery bridging group. The hemodynamics of the hepatic artery in the hepatic artery bridging group was measured using color Doppler ultrasound. Morphological changes in the bile canaliculus were observed by transmission electron microscopy. Cofilin, heat shock protein 27 and F-actin expression was detected by immunohistochemistry, Western blot, and real-time polymerase chain reaction. Terminal deoxynucleotidyl transferase-mediated nick end-labeling method was used to evaluate liver injury. RESULTS: The hemodynamics was not changed in the hepatic artery bridging group. The microvilli in the bile canaliculus were impaired in the two hepatic artery ischemia groups. The down-regulation of cofilin and F-actin and up-regulation of heat shock protein 27 were observed in the two hepatic artery ischemia groups, while there were no significant differences between thecontrol group and hepatic artery bridging group.CONCLUSION: Hepatic artery ischemia aggravates damage to bile canaliculi, and this damage can be diminished by a hepatic artery bridging duct.

Effect of exogenous hydrogen sulfide in the nucleus tractus solitarius on gastric motility in rats

BACKGROUND Hydrogen sulfide(H2S)is a recently discovered gaseous neurotransmitter in the nervous and gastrointestinal systems.It exerts its effects through multiple signaling pathways,impacting various physiological activities.The nucleus tractus solitarius(NTS),a vital nucleus involved in visceral sensation,was investigated in this study to understand the role of H2S in regulating gastric function in rats.AIM To examine whether H2S affects the nuclear factor kappa-B(NF-κB)and transient receptor potential vanilloid 1 pathways and the neurokinin 1(NK1)receptor in the NTS.METHODS Immunohistochemical and fluorescent double-labeling techniques were employed to identify cystathionine beta-synthase(CBS)and c-Fos co-expressed positive neurons in the NTS during rat stress.Gastric motility curves were recorded by inserting a pressure-sensing balloon into the pylorus through the stomach fundus.Changes in gastric motility were observed before and after injecting different doses of NaHS(4 nmol and 8 nmol),physiological saline,Capsazepine(4 nmol)+NaHS(4 nmol),pyrrolidine dithiocarbamate(PDTC,4 nmol)+NaHS(4 nmol),and L703606(4 nmol)+NaHS(4 nmol).RESULTS We identified a significant increase in the co-expression of c-Fos and CBS positive neurons in the NTS after 1 h and 3 h of restraint water-immersion stress compared to the expressions observed in the control group.Intra-NTS injection of NaHS at different doses significantly inhibited gastric motility in rats(P<0.01).However,injection of saline,first injection NF-κB inhibitor PDTC or transient receptor potential vanilloid 1(TRPV1)antagonist Capsazepine or NK1 receptor blockers L703606 and then injection NaHS did not produce significant changes(P>0.05).CONCLUSION NTS contains neurons co-expressing CBS and c-Fos,and the injection of NaHS into the NTS can suppress gastric motility in rats.This effect may be mediated by activating TRPV1 and NK1 receptors via the NF-κB channel.

Carbon cathode with heteroatom doping and ultrahigh surface area enabling enhanced capacitive behavior for potassium-ion hybrid capacitors

Potassium-ion hybrid capacitors(PIHCs)are widely regarded as highly promising energy storage devices,due to their exceptional energy density,impressive power density,and abundant potassium resources.Unfortunately,restricted by the inherent capacitive storage mechanism,the carbon cathodes possess a much lower specific capacity than battery-type anodes.Therefore,designing high-performance carbon cathodes is extremely urgent for the development of PIHCs.Herein,N,O codoped porous carbon(NOPC)was fabricated through the NaCl hard template method and combined KOH/melamine chemical activation technique,displaying the characteristics of abundant N/O content(4.7 at%/16.9 at%),ultrahigh specific surface area(3092 m^(2)g^(-1))and hierarchical pore network.The designed NOPC cathode delivers a high specific capacity(164.4 mAh.g^(-1)at 0.05 A.g^(-1))and superior cyclability(95.1%retention ratio at 2 A·g^(-1)over 2500 cycles).Notably,the adjustable ratio of micropores to mesopores facilitates the achievement of the optimal bal-ance between capacity and rate capability.Moreover,the pseudocapacitance can be further augmented through the incorporation of N/O functional groups.As expected,the graphite//NOPC based PIHC possesses a high energy density of 113 Wh·kg-at 747 W·kg^(-1)and excellent capacity retention of 84.4% fter 400 cycles at 1.0 A·g^(-1).This work introduces a novel strategy for designing carbon cathodes that enhances the electrochemical performance of PIHCs.

Identifying key genes associated with Hirschsprung's disease based on bioinformatics analysis of RNA-sequencing data

Background:Hirschsprung's disease (HSCR) is a type of megacolon induced by deficiency or dysfunction of ganglion cells in the distal intestine and is associated with developmental disorders of the enteric nervous system.To explore the mechanisms of HSCR,we analyzed the RNA-sequencing data of the expansion and the narrow segments of colon tissues separated from children with HSCR.Methods:RNA-sequencing of the expansion segments and the narrow segments of colon tissues isolated from children with HSCR was performed.After differentially expressed genes (DEGs) were identified using the edgeR package in R,functional and pathway enrichment analyses of DEGs were carried out using DAVID software.To further screen the key genes,protein-protein interaction (PPI) network and module analyses were conducted separately using Cytoscape software.Results:A total of 117 DEGs were identified in the expansion segment samples,including 47 up-regulated and 70 down-regulated genes.Functional enrichment analysis suggested that FOS and DUSP1 were implicated in response to endogenous stimulus.In the PPI network analysis,FOS (degree=20),EGR1 (degree=16),ATF3 (degree=9),NOS1 (degree=8),CCL5 (degree=8),DUSP1 (degree=7),CXCL3 (degree=6),VIP (degree=6),FOSB (degree=5),and NOS2 (degree=4) had higher degrees,which could interact with other genes.In addition,two significant modules (module 1 and module 2) were identified from the PPI network.Conclusion:Several genes (including FOS,EGR1,ATF3,NOS1,CCL5,DUSP1,CXCL3,VIP,FOSB,and NOS2) might be involved in the development of HSCR through their effect on the nervous system.