Liver fibrosis is a chronic liver injury resulting from factors like viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis, fatty liver disease, and cholestatic liver disease. Liver transplantation is currently the gold standard for treating severe liver diseases. However, it is limited by a shortage of donor organs and the necessity for lifelong immunosuppressive therapy. Mesenchymal stem cells (MSCs) can differentiate into various liver cells and enhance liver function when transplanted into patients due to their differentiation and proliferation capabilities. Therefore, it can be used as an alternative therapy for treating liver diseases, especially for liver cirrhosis, liver failure, and liver transplant complications. However, due to the potential tumorigenic effects of MSCs, researchers are exploring a new approach to treating liver fibrosis using extracellular vesicles (exosomes) secreted by stem cells. Many studies show that exosomes released by stem cells can promote liver injury repair through various pathways, contributing to the treatment of liver fibrosis. In this review, we focus on the molecular mechanisms by which stem cell exosomes affect liver fibrosis through different pathways and their potential therapeutic targets. Additionally, we discuss the advantages of exosome therapy over stem cell therapy and the possible future directions of exosome research, including the prospects for clinical applications and the challenges to be overcome.

Liver fibrosis is a chronic liver injury resulting from factors like viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis, fatty liver disease, and cholestatic liver disease. Liver transplantation is currently the gold standard for treating severe liver diseases. However, it is limited by a shortage of donor organs and the necessity for lifelong immunosuppressive therapy. Mesenchymal stem cells (MSCs) can differentiate into various liver cells and enhance liver function when transplanted into patients due to their differentiation and proliferation capabilities. Therefore, it can be used as an alternative therapy for treating liver diseases, especially for liver cirrhosis, liver failure, and liver transplant complications. However, due to the potential tumorigenic effects of MSCs, researchers are exploring a new approach to treating liver fibrosis using extracellular vesicles (exosomes) secreted by stem cells. Many studies show that exosomes released by stem cells can promote liver injury repair through various pathways, contributing to the treatment of liver fibrosis. In this review, we focus on the molecular mechanisms by which stem cell exosomes affect liver fibrosis through different pathways and their potential therapeutic targets. Additionally, we discuss the advantages of exosome therapy over stem cell therapy and the possible future directions of exosome research, including the prospects for clinical applications and the challenges to be overcome.

Liver fibrosis is a chronic liver injury resulting from factors like viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis, fatty liver disease, and cholestatic liver disease. Liver transplantation is currently the gold standard for treating severe liver diseases. However, it is limited by a shortage of donor organs and the necessity for lifelong immunosuppressive therapy. Mesenchymal stem cells (MSCs) can differentiate into various liver cells and enhance liver function when transplanted into patients due to their differentiation and proliferation capabilities. Therefore, it can be used as an alternative therapy for treating liver diseases, especially for liver cirrhosis, liver failure, and liver transplant complications. However, due to the potential tumorigenic effects of MSCs, researchers are exploring a new approach to treating liver fibrosis using extracellular vesicles (exosomes) secreted by stem cells. Many studies show that exosomes released by stem cells can promote liver injury repair through various pathways, contributing to the treatment of liver fibrosis. In this review, we focus on the molecular mechanisms by which stem cell exosomes affect liver fibrosis through different pathways and their potential therapeutic targets. Additionally, we discuss the advantages of exosome therapy over stem cell therapy and the possible future directions of exosome research, including the prospects for clinical applications and the challenges to be overcome.

Objectives:Comparative analysis of the beagles acute-phase electrocardiographic,hemodynamic,left ventricular flow field status,and energy consumption characteristics of pacing at different sites of conduction system may help to elucidate the scientific mechanism of left bundle branch pacing(LBBP)as a option of physiological pacing therapy.Methods:Eight healthy adult beagles were used in this study.Initially,an active fixation lead was implanted in the right atrial appendage,followed by implantation of another active fixation lead at the right ventricular apex,distal His bundle,and left bundle septal branch,respectively.After connecting a dual-chamber pacemaker,electrocardiographic and acute phase hemodynamic parameters under sinus rhythm,right ventricular apex pacing(RVAP),distal His bundle pacing(DHBP),and LBBP states were collected and analyzed.Three complete cardiac cycles of standard apical three-chamber color Doppler dynamic images were acquired under vector flow mapping(VFM)mode.Offline analysis was performed on obtained parameters including isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,atrial contraction period,and left ventricular intracavitary energy consumption.These parameters were compared under pacing at different sites and the linear correlations of major parameters were analyzed.Results:The QRS duration of baseline intrinsic sinus rhythm,RVAP,DHBP and LBBP were(45.0±4.0)ms,(98.4±6.2)ms,(50.0±4.5)ms and(62.0±4.7)ms,respectively.The LBBP-QRS duration was significantly wider than intrinsic sinus rhythm and DHBP,but significantly narrower than RVAP(all P<0.01).Compared with baseline AOO mode(the pacing rate was performed at 10 beats/min above the intrinsic heart rate),the change of acute phase maximum left ventricular pressure rise rate(LVdP/dtmax)in RVAP,DHBP and LBBP was([-7.89±5.67]% ),([0.74±2.05]% )and([-0.14±3.59]% ),respectively.There was no significant difference in LVdP/dtmax changes between DHBP and LBBP(P=0.667),but both pacing modalities were significantly better than RVAP(all P<0.01).The average energy consumption of the left ventricle under RVAP was significantly higher than that of intrinsic sinus rhythm,DHBP,and LBBP in isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,and atrial contraction period(all P<0.01).However,there was no statistically significant difference in energy consumption among intrinsic sinus rhythm,DHBP,and LBBP during the above five phases(all P>0.05).DHBP and LBBP did not show a significant increase in the number of left ventricular vortices,vortex area,and circulation intensity compared to intrinsic sinus rhythm,and LBBP did not show a significant increase in vortex area and circulation intensity compared to DHBP.Conclusions:Although LBBP canines significantly prolonged the paced QRS duration,it showed no significant differences in acute phase left ventricular hemodynamics,left ventricular flow field status,and energy consumption compared to intrinsic sinus rhythm and DHBP.Performance of LBBP was superior to RVAP.This study may contribute to revealing the theoretical basis of LBBP as a feasible physiological pacing therapy.

Objective:To investigate the application value of needle-knife accurate fistulo-tomy (NKAF) for difficult biliary cannulation during endoscopic retrograde cholangiopancreato-graphy (ERCP).Methods:The retrospective and descriptive study was conducted. The clinicopatho-logical data of 137 patients with difficult biliary cannulation during ERCP at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between January 2021 and December 2022 were collected. There were 51 males and 86 females, aged (69±13)years. All 137 patients received NKAF for cannulation during ERCP. Observation indicators: (1) surgical situations; (2) complications. Measurement data with normal distribution were represented as Mean± SD. Count data were repre-sented as absolute numbers. Results:(1) Surgical situations. Of 137 patients, 136 cases had succe-ssful cannulation, 1 case had failed cannulation with NKAF following unsuccessful double-guidewire technique. In the 136 successful cases, the endoscope was straightened in 42 cases, left in a long position in 37 cases, and maintained in the standard position in 57 cases. The cannulation time was (90±8)s. (2) Complications. The serum amylase at postoperative 6 hours in the 136 successful cases was (163±23)U/L. No patient developed post-ERCP pancreatitis. Of the 136 patients with successful cannulation, one case experienced post-sphincterotomy bleeding, which was observed oozing from the papillary orifice on emergency gastroscopy. The patient was successfully controlled with endoscopic clips.Conclusion:NKAF is safe and effective for difficult biliary cannulation during ERCP.

INTRODUCTION: Adolescent depression is prevalent, and teen suicide rates are on the rise locally. A systemic review to understand associated risk and protective factors is important to strengthen measures for the prevention and early detection of adolescent depression and suicide in Singapore. This systematic review aims to identify the factors associated with adolescent depression in Singapore. METHODS: A systematic search on the following databases was performed on 21 May 2020: PubMed, EMBASE and PsycINFO. Full texts were reviewed for eligibility, and the included studies were appraised for quality using the Newcastle Ottawa Scale. Narrative synthesis of the finalised articles was performed through thematic analysis. RESULTS: In total, eight studies were included in this review. The four factors associated with adolescent depression identified were: (1) sociodemographic factors (gender, ethnicity); (2) psychological factors, including childhood maltreatment exposure and psychological constructs (hope, optimism); (3) coexisting chronic medical conditions (asthma); and (4) lifestyle factors (sleep inadequacy, excessive internet use and pathological gaming). CONCLUSION The identified factors were largely similar to those reported in the global literature, except for sleep inadequacy along with conspicuously absent factors such as academic stress and strict parenting, which should prompt further research in these areas. Further research should focus on current and prospective interventions to improve mental health literacy, targeting sleep duration, internet use and gaming, and mitigating the risk of depression in patients with chronic disease in the primary care and community setting.
Humans ; Singapore/epidemiology* ; Adolescent ; Risk Factors ; Depression/etiology* ; Protective Factors ; Male ; Female ; Life Style ; Suicide

INTRODUCTION: Obstructive sleep apnoea (OSA) is common in Singapore, with moderate to severe OSA affecting around 30% of residents. These consensus statements aim to provide scientifically grounded recommendations for the management of OSA, standar-dise the management of OSA in Singapore and promote multidisciplinary collaboration. METHOD: An expert panel, which was convened in 2024, identified several areas of OSA management that require guidance. The expert panel reviewed the current literature and developed consensus statements, which were later independently voted on using a 3-point Likert scale (agree, neutral or disagree). Consensus (total ratings of agree and neutral) was set a priori at ≥80% agreement. Any statement not reaching consensus was excluded. RESULTS: The final consensus included 49 statements that provide guidance on the screening, diagnosis and management of adults with OSA. Additionally, 23 statements on the screening, diagnosis and management of paediatric OSA achieved consensus. These 72 consensus statements considered not only the latest clinical evidence but also the benefits and harms, resource implications, feasibility, acceptability and equity impact of the recommendations. CONCLUSION The statements presented in this paper aim to guide clinicians based on the most updated evidence and collective expert opinion from sleep specialists in Singapore. These recommendations should augment clinical judgement rather than replace it. Management decisions should be individualised, taking into account the patient's clinical characteristics, as well as patient and caregiver concerns and preferences.
Humans ; Sleep Apnea, Obstructive/diagnosis* ; Singapore ; Consensus ; Adult

Objective:To explore the impact of adolescent mental health status on smartphone addiction, and construct a predictive model for smartphone addiction based on the eXtreme Gradient Boosting(XGBoost) algorithm and multivariate Logistic regression.Methods:In April 2023, a cross-sectional survey was conducted among 14 666 adolescents.All participants were systematically evaluated using a self-developed general information questionnaire, the middle school student mental health scale(MSSMHS), the adolescents self-harm scale(ASHS), the interaction anxiousness scale(IAS), the mobile phone addiction index(MPAI), the middle school students shame scale(MSSS), the UCLA loneliness scale(UCLA-LS), the multidimensional peer victimization scale(MPVS), and the basic psychological needs scale(BPNS).R software version 4.3.2 was used for data analysis. Participants were randomly divided into training set and validation set at the ratio of 7∶3.The XGBoost model and multivariate logistic regression model were constructed to predict the risk of smartphone addiction, and a nomogram was plotted.Model performance was evaluated using the Hosmer-Lemeshow test, area under the curve(AUC), and accuracy(ACC).Results:(1) A total of 14 036 high school students were included in the study, with 5 069(36.1%) exhibited smartphone addiction.The training set comprised 9 826 students, with 3 549(36.1%) being smartphone addicts.The validation set included 4 210 students, with 1 520(36.1%) being smartphone addicts.(2) The XGBoost model identified shame-proneness and social anxiety as the two main predictors of smartphone addiction.(3) Multivariate Logistic regression analysis revealed that anxiety( B=0.328, OR(95% CI)=1.39(1.07-1.81), P=0.015), interpersonal sensitivity( B=0.311, OR(95% CI)=1.36(1.05-1.77), P=0.018), learning pressure( B=0.606, OR(95% CI)=1.83(1.46-2.31), P<0.001), mood swings( B=0.775, OR(95% CI)=2.17(1.70-2.78), P<0.001), social anxiety( B=0.024, OR(95% CI)=1.02(1.01-1.04), P<0.001), shame-proneness( B=0.049, OR(95% CI)=1.05(1.04-1.06), P<0.001), and peer victimization( B=0.037, OR(95% CI)=1.04(1.02-1.06), P<0.001) were significant predictors of smartphone addiction.(4) The ACC and AUC values of the XGBoost model were 0.890 and 0.929 in the training set, and 0.865 and 0.864 in the validation set, respectively.The multivariate Logistic regression model achieved ACC and AUC values of 0.870 and 0.854 in the training set, and 0.867 and 0.859 in the validation set, respectively. Conclusion:Anxiety, interpersonal sensitivity, learning pressure, mood swings, social anxiety, shame-proneness, and peer victimization are identified risk predictors of smartphone addiction in high school adolescents.

Objectives:Comparative analysis of the beagles acute-phase electrocardiographic,hemodynamic,left ventricular flow field status,and energy consumption characteristics of pacing at different sites of conduction system may help to elucidate the scientific mechanism of left bundle branch pacing(LBBP)as a option of physiological pacing therapy.Methods:Eight healthy adult beagles were used in this study.Initially,an active fixation lead was implanted in the right atrial appendage,followed by implantation of another active fixation lead at the right ventricular apex,distal His bundle,and left bundle septal branch,respectively.After connecting a dual-chamber pacemaker,electrocardiographic and acute phase hemodynamic parameters under sinus rhythm,right ventricular apex pacing(RVAP),distal His bundle pacing(DHBP),and LBBP states were collected and analyzed.Three complete cardiac cycles of standard apical three-chamber color Doppler dynamic images were acquired under vector flow mapping(VFM)mode.Offline analysis was performed on obtained parameters including isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,atrial contraction period,and left ventricular intracavitary energy consumption.These parameters were compared under pacing at different sites and the linear correlations of major parameters were analyzed.Results:The QRS duration of baseline intrinsic sinus rhythm,RVAP,DHBP and LBBP were(45.0±4.0)ms,(98.4±6.2)ms,(50.0±4.5)ms and(62.0±4.7)ms,respectively.The LBBP-QRS duration was significantly wider than intrinsic sinus rhythm and DHBP,but significantly narrower than RVAP(all P<0.01).Compared with baseline AOO mode(the pacing rate was performed at 10 beats/min above the intrinsic heart rate),the change of acute phase maximum left ventricular pressure rise rate(LVdP/dtmax)in RVAP,DHBP and LBBP was([-7.89±5.67]% ),([0.74±2.05]% )and([-0.14±3.59]% ),respectively.There was no significant difference in LVdP/dtmax changes between DHBP and LBBP(P=0.667),but both pacing modalities were significantly better than RVAP(all P<0.01).The average energy consumption of the left ventricle under RVAP was significantly higher than that of intrinsic sinus rhythm,DHBP,and LBBP in isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,and atrial contraction period(all P<0.01).However,there was no statistically significant difference in energy consumption among intrinsic sinus rhythm,DHBP,and LBBP during the above five phases(all P>0.05).DHBP and LBBP did not show a significant increase in the number of left ventricular vortices,vortex area,and circulation intensity compared to intrinsic sinus rhythm,and LBBP did not show a significant increase in vortex area and circulation intensity compared to DHBP.Conclusions:Although LBBP canines significantly prolonged the paced QRS duration,it showed no significant differences in acute phase left ventricular hemodynamics,left ventricular flow field status,and energy consumption compared to intrinsic sinus rhythm and DHBP.Performance of LBBP was superior to RVAP.This study may contribute to revealing the theoretical basis of LBBP as a feasible physiological pacing therapy.

Objective:To explore the impact of adolescent mental health status on smartphone addiction, and construct a predictive model for smartphone addiction based on the eXtreme Gradient Boosting(XGBoost) algorithm and multivariate Logistic regression.Methods:In April 2023, a cross-sectional survey was conducted among 14 666 adolescents.All participants were systematically evaluated using a self-developed general information questionnaire, the middle school student mental health scale(MSSMHS), the adolescents self-harm scale(ASHS), the interaction anxiousness scale(IAS), the mobile phone addiction index(MPAI), the middle school students shame scale(MSSS), the UCLA loneliness scale(UCLA-LS), the multidimensional peer victimization scale(MPVS), and the basic psychological needs scale(BPNS).R software version 4.3.2 was used for data analysis. Participants were randomly divided into training set and validation set at the ratio of 7∶3.The XGBoost model and multivariate logistic regression model were constructed to predict the risk of smartphone addiction, and a nomogram was plotted.Model performance was evaluated using the Hosmer-Lemeshow test, area under the curve(AUC), and accuracy(ACC).Results:(1) A total of 14 036 high school students were included in the study, with 5 069(36.1%) exhibited smartphone addiction.The training set comprised 9 826 students, with 3 549(36.1%) being smartphone addicts.The validation set included 4 210 students, with 1 520(36.1%) being smartphone addicts.(2) The XGBoost model identified shame-proneness and social anxiety as the two main predictors of smartphone addiction.(3) Multivariate Logistic regression analysis revealed that anxiety( B=0.328, OR(95% CI)=1.39(1.07-1.81), P=0.015), interpersonal sensitivity( B=0.311, OR(95% CI)=1.36(1.05-1.77), P=0.018), learning pressure( B=0.606, OR(95% CI)=1.83(1.46-2.31), P<0.001), mood swings( B=0.775, OR(95% CI)=2.17(1.70-2.78), P<0.001), social anxiety( B=0.024, OR(95% CI)=1.02(1.01-1.04), P<0.001), shame-proneness( B=0.049, OR(95% CI)=1.05(1.04-1.06), P<0.001), and peer victimization( B=0.037, OR(95% CI)=1.04(1.02-1.06), P<0.001) were significant predictors of smartphone addiction.(4) The ACC and AUC values of the XGBoost model were 0.890 and 0.929 in the training set, and 0.865 and 0.864 in the validation set, respectively.The multivariate Logistic regression model achieved ACC and AUC values of 0.870 and 0.854 in the training set, and 0.867 and 0.859 in the validation set, respectively. Conclusion:Anxiety, interpersonal sensitivity, learning pressure, mood swings, social anxiety, shame-proneness, and peer victimization are identified risk predictors of smartphone addiction in high school adolescents.