Introduction: Polypharmacy and potentially inappropriate prescribing (PIP) are increasingly recognised as important contributors to medication -related harm among older adults. However, published national data on the prevalence of polypharmacy and PIP in Brunei Darussalam are unavailable. The objectives of this study was to determine the prevalence of polypharmacy and PIP among adults aged 65 years and above in Brunei Darussalam using Screening Tool of Older Persons ’ potentially inappropriate Prescriptions (STOPP) version 2 criteria. Materials and Methods: A retrospective cross -sectional study was conducted using data from the Brunei Healthcare Information Management System (Bru -HIMS). A stratified proportional random sample of 2,000 older adults with documented medical encounters in 2016 was selected. Polypharmacy was defined as the concurrent use of five or more medications. PIP was assessed using STOPP version 2 criteria. Descriptive statistics were used to summarise prescribing patterns. Results: Of the 2000 older adults included (mean age 73.0 ± 6.6 years), 1,181 (59.1%) had polypharmacy. Among those with polypharmacy, 1,057 (89.5%) could be assessed using STOPP criteria, and 206 (19.5%) had at least one PIP. The most frequently identified PIPs involved prolonged use of proton pump inhibitors for uncomplicated peptic ulcer disease at full therapeutic dosage for more than eight weeks, where dose reduction, discontinuation, or transition to maintenance therapy (e.g. H2 receptor antagonists) is indicated, prescribing without evidence -based indication, duplication of drug classes, use of ACE inhibitors or angiotensin receptor blockers in patients with hyperkalaemia, and use of first -generation antihistamines. Conclusion: Polypharmacy and PIP are common among older adults in Brunei Darussalam. The findings highlight the need for systematic medication review and deprescribing strategies to optimise pharmacotherapy and improve medication safety in older populations

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objectives: Hip fracture is a global public concern exhibiting high mortality rates but often underrecognized. We compared the mortality rates, risk, and secular trend of hip fractures with common cancers in females and males, aiming to call attention to hip fractures. Methods: In 2010–2020, 193,767 patients with the first diagnosed hip fractures and the top 5 prevalent cancers in each sex and aged 50 years and above were included. Age-standardized mortality rates were adjusted to the WHO Standard Population and the sex-specific relative risk of mortality was computed using Cox proportional hazards models, adjusted for potential confounders. The trend analyses used joinpoint regression to compute annual percent changes in age-standardized mortality rates. Results The 1-year and 5-year age-standardized mortality rates and sex-specific mortality risk of hip fracture are greater than those of breast cancer (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.90 to 0.97) and thyroid cancer (HR: 0.55, 95% CI: 0.47 to 0.64) in females and prostate cancer (HR: 0.56, 95% CI: 0.53 to 0.58) in males. Moreover, mortality rates in lung cancer, male liver cancer, female breast cancer, and male prostate cancer have decreased in the past decade. For hip fracture, the mortality rates have significantly decreased in females, while in males, we observed only a decreasing trend in 1-year hip fracture mortality, not in 5-year Conclusions: Hip fractures exhibit higher mortality compared to female breast and thyroid cancers and male prostate cancer. More attention is needed to enhance the management and prevention of hip fractures.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objectives: Hip fracture is a global public concern exhibiting high mortality rates but often underrecognized. We compared the mortality rates, risk, and secular trend of hip fractures with common cancers in females and males, aiming to call attention to hip fractures. Methods: In 2010–2020, 193,767 patients with the first diagnosed hip fractures and the top 5 prevalent cancers in each sex and aged 50 years and above were included. Age-standardized mortality rates were adjusted to the WHO Standard Population and the sex-specific relative risk of mortality was computed using Cox proportional hazards models, adjusted for potential confounders. The trend analyses used joinpoint regression to compute annual percent changes in age-standardized mortality rates. Results The 1-year and 5-year age-standardized mortality rates and sex-specific mortality risk of hip fracture are greater than those of breast cancer (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.90 to 0.97) and thyroid cancer (HR: 0.55, 95% CI: 0.47 to 0.64) in females and prostate cancer (HR: 0.56, 95% CI: 0.53 to 0.58) in males. Moreover, mortality rates in lung cancer, male liver cancer, female breast cancer, and male prostate cancer have decreased in the past decade. For hip fracture, the mortality rates have significantly decreased in females, while in males, we observed only a decreasing trend in 1-year hip fracture mortality, not in 5-year Conclusions: Hip fractures exhibit higher mortality compared to female breast and thyroid cancers and male prostate cancer. More attention is needed to enhance the management and prevention of hip fractures.

Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.
Reperfusion Injury/drug therapy* ; Reactive Oxygen Species/metabolism* ; Reactive Nitrogen Species/metabolism* ; Humans ; Liver/drug effects* ; Animals ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

Somatostatin receptor 1 (SSTR1) is a crucial therapeutic target for various neuroendocrine and oncological disorders. Current SSTR1-targeted treatments, including the first-generation somatostatin analog lanreotide (Lan) and the second-generation analog pasireotide (Pas), show promise but encounter challenges related to selectivity and efficacy. This study presents high-resolution cryo-electron microscopy structures of SSTR1 complexed with Lan or Pas, revealing the distinct mechanisms of ligand-binding and activation. These structures illustrate unique conformational changes in the SSTR1 orthosteric pocket induced by each ligand, which are critical for receptor activation and ligand selectivity. Combined with the biochemical assays and molecular dynamics simulations, our results provide a comparative analysis of binding characteristics within the SSTR family, highlighting subtle differences in SSTR1 activation by Lan and Pas. These insights pave the way for designing next-generation therapies with enhanced efficacy and reduced side effects through improved receptor subtype selectivity.

Adenosine-to-inosine (A-to-I), one of the most prevalent RNA modifications, has recently garnered significant attention. The A-to-I modification actively contributes to biological and pathological processes by affecting the structure and function of various RNA molecules, including double-stranded RNA, transfer RNA, microRNA, and viral RNA. Increasing evidence suggests that A-to-I plays a crucial role in the development of human disease, particularly in cancer, and aberrant A-to-I levels are closely associated with tumorigenesis and progression through regulation of the expression of multiple oncogenes and tumor suppressor genes. Currently, the underlying molecular mechanisms of A-to-I modification in cancer are not comprehensively understood. Here, we review the latest advances regarding the A-to-I editing pathways implicated in cancer, describing their biological functions and their connections to the disease.
Humans ; Adenosine/genetics* ; Inosine/genetics* ; RNA Editing ; Neoplasms/pathology* ; Animals ; MicroRNAs/metabolism*

Objectives: Hip fracture is a global public concern exhibiting high mortality rates but often underrecognized. We compared the mortality rates, risk, and secular trend of hip fractures with common cancers in females and males, aiming to call attention to hip fractures. Methods: In 2010–2020, 193,767 patients with the first diagnosed hip fractures and the top 5 prevalent cancers in each sex and aged 50 years and above were included. Age-standardized mortality rates were adjusted to the WHO Standard Population and the sex-specific relative risk of mortality was computed using Cox proportional hazards models, adjusted for potential confounders. The trend analyses used joinpoint regression to compute annual percent changes in age-standardized mortality rates. Results The 1-year and 5-year age-standardized mortality rates and sex-specific mortality risk of hip fracture are greater than those of breast cancer (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.90 to 0.97) and thyroid cancer (HR: 0.55, 95% CI: 0.47 to 0.64) in females and prostate cancer (HR: 0.56, 95% CI: 0.53 to 0.58) in males. Moreover, mortality rates in lung cancer, male liver cancer, female breast cancer, and male prostate cancer have decreased in the past decade. For hip fracture, the mortality rates have significantly decreased in females, while in males, we observed only a decreasing trend in 1-year hip fracture mortality, not in 5-year Conclusions: Hip fractures exhibit higher mortality compared to female breast and thyroid cancers and male prostate cancer. More attention is needed to enhance the management and prevention of hip fractures.

Objectives: Hip fracture is a global public concern exhibiting high mortality rates but often underrecognized. We compared the mortality rates, risk, and secular trend of hip fractures with common cancers in females and males, aiming to call attention to hip fractures. Methods: In 2010–2020, 193,767 patients with the first diagnosed hip fractures and the top 5 prevalent cancers in each sex and aged 50 years and above were included. Age-standardized mortality rates were adjusted to the WHO Standard Population and the sex-specific relative risk of mortality was computed using Cox proportional hazards models, adjusted for potential confounders. The trend analyses used joinpoint regression to compute annual percent changes in age-standardized mortality rates. Results The 1-year and 5-year age-standardized mortality rates and sex-specific mortality risk of hip fracture are greater than those of breast cancer (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.90 to 0.97) and thyroid cancer (HR: 0.55, 95% CI: 0.47 to 0.64) in females and prostate cancer (HR: 0.56, 95% CI: 0.53 to 0.58) in males. Moreover, mortality rates in lung cancer, male liver cancer, female breast cancer, and male prostate cancer have decreased in the past decade. For hip fracture, the mortality rates have significantly decreased in females, while in males, we observed only a decreasing trend in 1-year hip fracture mortality, not in 5-year Conclusions: Hip fractures exhibit higher mortality compared to female breast and thyroid cancers and male prostate cancer. More attention is needed to enhance the management and prevention of hip fractures.