Jin-Yi Wan

Background: The Asia-Pacific region has the fastest metabolic disease transition globally, yet burden analyses remain global or sub-regional, obscuring the country-level heterogeneity that should guide differentiated prevention and treatment-capacity planning. Type 2 diabetes (T2DM), hypertension, obesity, hyperlipidaemia, and metabolic dysfunction-associated steatotic liver disease (MASLD) share a common upstream exposure in the region’s nutrition transition. No study has combined country-level epidemiological phenotyping, demographic decomposition, sociodemographic frontier analysis, and projection beyond 2030 for this five-condition cluster. We characterised the burden, structure, and trajectory of these conditions across 54 Asia-Pacific countries and territories to identify where resource allocation is most urgently needed.Methods: Using Global Burden of Disease (GBD) 2023 estimates, we analysed disability-adjusted life-years (DALYs) and mortality for T2DM, hypertension, obesity, hyperlipidaemia, and MASLD in individuals aged 15 years and older across 54 Asia-Pacific countries and territories, 1990–2023. We applied joinpoint regression and age-period-cohort (APC) analysis to characterise temporal trends, hierarchical clustering to stratify countries into epidemiological phenotypes, Das Gupta demographic decomposition to partition absolute burden change into population growth, ageing, and genuine rate change, quantile regression against the Socio-demographic Index (SDI) to identify burden unexplained by development, and Bayesian age-period-cohort (BAPC) models with integrated nested Laplace approximations to project burden to 2050.Findings: Age-standardised DALY rates diverged: obesity (estimated annual percentage change [EAPC] +0.59%, 95% uncertainty interval [UI] 0.51–0.66) and T2DM (+0.54%, 0.51–0.58) rose while hypertension (−1.18%, −1.23 to −1.12) and hyperlipidaemia (−1.11%, −1.17 to −1.05) declined, and MASLD increased marginally (+0.17%, 0.10–0.24). Nauru recorded the region’s highest hypertension, obesity, and hyperlipidaemia rates, and the Republic of Korea the lowest hypertension and hyperlipidaemia rates. Hierarchical clustering resolved five geographically coherent phenotypes, from an obesity-driven Oceanian small-island cluster to a stabilising East Asian and high-income cluster. Genuine increases in age-specific rates, distinct from population growth and ageing, contributed 38.9% of the obesity DALY rise in South Asia and 37.4% in Southeast Asia; India recorded the region’s fastest obesity EAPC (+4.77%). Oceanian phenotypes carried excess burden above their sociodemographic development level. Absolute burden is projected to rise across all five conditions to 2050, concentrated in adults aged 65 years and older.Interpretation: The Asia-Pacific metabolic burden is geographically structured, not a single regional narrative, and regional aggregates risk misallocating resources by treating it as uniform. The five phenotypes require differentiated responses: structural food environment reform in Oceania, expanded dietary and physical activity policy in South and Southeast Asia, and sustained investment in the institutional mechanisms underlying the East Asian and Australasian success trajectories. Health systems across all phenotypes must simultaneously sustain preventive investment and expand treatment capacity to absorb the demographically driven burden growth projected through 2050.

Background: The Asia-Pacific region has the fastest metabolic disease transition globally, yet burden analyses remain global or sub-regional, obscuring the country-level heterogeneity that should guide differentiated prevention and treatment-capacity planning. Type 2 diabetes (T2DM), hypertension, obesity, hyperlipidaemia, and metabolic dysfunction-associated steatotic liver disease (MASLD) share a common upstream exposure in the region’s nutrition transition. No study has combined country-level epidemiological phenotyping, demographic decomposition, sociodemographic frontier analysis, and projection beyond 2030 for this five-condition cluster. We characterised the burden, structure, and trajectory of these conditions across 54 Asia-Pacific countries and territories to identify where resource allocation is most urgently needed.Methods: Using Global Burden of Disease (GBD) 2023 estimates, we analysed disability-adjusted life-years (DALYs) and mortality for T2DM, hypertension, obesity, hyperlipidaemia, and MASLD in individuals aged 15 years and older across 54 Asia-Pacific countries and territories, 1990–2023. We applied joinpoint regression and age-period-cohort (APC) analysis to characterise temporal trends, hierarchical clustering to stratify countries into epidemiological phenotypes, Das Gupta demographic decomposition to partition absolute burden change into population growth, ageing, and genuine rate change, quantile regression against the Socio-demographic Index (SDI) to identify burden unexplained by development, and Bayesian age-period-cohort (BAPC) models with integrated nested Laplace approximations to project burden to 2050.Findings: Age-standardised DALY rates diverged: obesity (estimated annual percentage change [EAPC] +0.59%, 95% uncertainty interval [UI] 0.51–0.66) and T2DM (+0.54%, 0.51–0.58) rose while hypertension (−1.18%, −1.23 to −1.12) and hyperlipidaemia (−1.11%, −1.17 to −1.05) declined, and MASLD increased marginally (+0.17%, 0.10–0.24). Nauru recorded the region’s highest hypertension, obesity, and hyperlipidaemia rates, and the Republic of Korea the lowest hypertension and hyperlipidaemia rates. Hierarchical clustering resolved five geographically coherent phenotypes, from an obesity-driven Oceanian small-island cluster to a stabilising East Asian and high-income cluster. Genuine increases in age-specific rates, distinct from population growth and ageing, contributed 38.9% of the obesity DALY rise in South Asia and 37.4% in Southeast Asia; India recorded the region’s fastest obesity EAPC (+4.77%). Oceanian phenotypes carried excess burden above their sociodemographic development level. Absolute burden is projected to rise across all five conditions to 2050, concentrated in adults aged 65 years and older.Interpretation: The Asia-Pacific metabolic burden is geographically structured, not a single regional narrative, and regional aggregates risk misallocating resources by treating it as uniform. The five phenotypes require differentiated responses: structural food environment reform in Oceania, expanded dietary and physical activity policy in South and Southeast Asia, and sustained investment in the institutional mechanisms underlying the East Asian and Australasian success trajectories. Health systems across all phenotypes must simultaneously sustain preventive investment and expand treatment capacity to absorb the demographically driven burden growth projected through 2050.

Background: Gastrointestinal intolerance is the leading cause of glucagon-like peptide-1 receptor agonist (GLP-1RA) discontinuation; however, clinicians lack within-class evidence on which symptoms a given agent is most likely to provoke. We aimed to characterise symptom-level gastrointestinal adverse event profiles and within-class heterogeneity across GLP-1RAs to inform initial agent selection.Methods: We searched PubMed, Embase, Web of Science, and the Cochrane Library from database inception to Dec 20, 2025, for randomised controlled trials comparing GLP-1RAs with controls or with one another in adults with type 2 diabetes, type 1 diabetes, overweight or obesity, or metabolic dysfunction-associated steatotic liver disease. The primary outcome was gastrointestinal treatment-emergent adverse events; secondary outcomes were the individual gastrointestinal symptoms and hepatobiliary and pancreatic events. Three reviewers extracted data independently. We did a random-effects network meta-analysis with a frequentist graph-theory approach and rated certainty of evidence using GRADE. The study was registered with PROSPERO (CRD42024499051).Findings: Of 20 181 records, 225 randomised controlled trials with 119 474 participants and 35 GLP-1RA agents were included. High to moderate certainty evidence supported a class-wide gastrointestinal risk hierarchy in which individual agents carried distinct symptom-level profiles. Tirzepatide and semaglutide, the most prescribed agents, showed divergent signatures: tirzepatide for diarrhoea (OR 3·74, 95% CI 2·53 to 5·54) and gastro-oesophageal reflux disease (OR 3·79, 95% CI 1·69 to 8·51), and semaglutide for dyspepsia (OR 4·24, 95% CI 3·08 to 5·82) and abdominal pain (OR 3·76, 95% CI 2·58 to 5·48), all with high certainty. The investigational oral agent orforglipron showed the highest treatment-emergent burden (OR 12·33, 95% CI 2·95 to 51·56; moderate certainty). Hepatobiliary signals were modest.Interpretation: Symptom-level gastrointestinal adverse event profiles are agent-specific across the GLP-1RA class, with sufficient certainty to inform initial agent selection. Symptom-informed prescribing could mitigate the gastrointestinal-driven discontinuation that limits the long-term benefit of these therapies.

The rhubarb root and the senna leaf are two commonly used laxative herbs for functional constipation, containing dianthrones and free anthraquinones. As a free anthraquinone, emodin is a crucial constituent isolated from laxative botanicals, and it is particularly abundant in the rhubarb root, a key ingredient in the classic Chinese medicine formula MaZiRenWan (or herbal medicine CDD-2101). This study explored emodin’s anti-malignancy, anti-inflammation, and underlying mechanisms. We examined emodin and other anthraquinones on human colorectal cancer cell proliferation, then used Apc ^Min/ [Formula: see text] mice to assess effects on animal lifespan, intestinal tumor multiplicity, inflammatory cytokines, and adaptive immunity. Results showed MaZiRenWan extract inhibited HCT-116/HT-29 human cancer cells. However, two primary dianthrone sennosides, sennoside A and sennoside B, did not demonstrate such pronounced effects. Three free anthraquinones, emodin, aloe-emodin, and rhein, displayed antiproliferative effects on cancer cells, which were observed to be significantly concentration- and time-dependent, with emodin demonstrating the strongest action. Emodin was found to induce cell cycle arrest during the S-G2/M phases and trigger apoptosis. In vivo, emodin extended Apc ^{Min/[Formula: see text]} mice lifespan, reduced gut tumors, downregulated gut tissue levels of key pro-inflammatory cytokines such as IL-1α, IL-1β, IL-6, IL-17A, IL-8, G-CSF, and GM-CSF; this result was supported by the IL-8 secretion test. Emodin had no inhibitory effect on regulatory Treg cell differentiation, yet it effectively suppressed the Th1 and the Th17 cell differentiation. In conclusion, emodin prevents colorectal cancer via inhibiting cell growth, anti-inflammation, and adaptive immunity modulation, highlighting its potential in inflammation-associated colorectal cancer prevention.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), a prevalent chronic liver disorder, imposes a substantial global clinical and economic burden. Emerging evidence underscores inflammatory bowel disease (IBD) as a significant independent risk factor for MASLD. However, the global burden and trends of MASLD-IBD comorbidity remain largely obscured. This study aims to evaluate the global burden of MASLD-IBD from 1990 to 2021 and to project its trajectory to 2050. The findings will inform the development of proactive public health strategies Methods: Leveraging the Global Burden of Disease (GBD) 2021 database, we quantified IBD’s contribution to MASLD via population-attributable fractions. We analyzed the global prevalence, mortality, and disability-adjusted life years (DALYs), stratifying by socio-demographic index (SDI), sex, and age. Estimated annual percentage change (EAPC) assessed 1990–2021 trends; Bayesian age-period-cohort modeling projected 2050 trajectories. Results: In 2021, the global age-standardized prevalence of MASLD-IBD comorbidity reached 171.7 cases (95% uncertainty interval [UI], 157.3–187.1), with a corresponding DALY rate of 0.5 cases (95% UI, 0.4–0.6) per 10 million population. High-income regions, including North America, Australia, and Western Europe, bore the highest burden. From 1990 to 2021, 20 out of 21 GBD regions exhibited escalating age-standardized prevalence and DALY rates, most markedly in East Asia (prevalence EAPC = 3.18; 95% confidence interval [CI], 2.59–3.77) and East Europe (DALY EAPC = 4.05; 95% CI, 3.32–4.79). Middle SDI regions saw the largest absolute increases, with mortality mirroring DALY trends. Adults ≥ 60 years bore disproportionately higher burdens. By 2050, projections suggest divergent gender trends of rising female burden versus declining male rates. Conclusions: MASLD-IBD comorbidity burdens have risen globally over three decades, necessitating targeted interventions, particularly for ageing populations and high-risk regions. Gender-specific strategies will be critical for mitigating future impacts.

Intestinal immunity at molecular, cellular, and multi-omic levels. The ten included articles here explore diverse mechanisms from mitochondrial homeostasis, cell death mechanisms, microbiome crosstalk, to clinical translation, collectively advancing natural products from empiric remedies to rationally based therapeutics.As the forefront of intestinal defense, disruption of the epithelial barrier initiates Future research priorities for this field encompass several key areas. First, developing precision-targeted nanoparticle formulations to achieve maximum bioavailability and tissue-selective targeting. Second, engineering protective microbiomes by synergistic combinations of phytochemical prebiotics, probiotics, and other applicable approaches. Third, identifying additional natural products with the ability to modulate intestinal mucosal immunity and establishing a multidimensional methodological approach to elucidate the mechanisms of action, thereby laying a foundation for further clinical applications. Fourth, conducting rigorous clinical benchmarking via randomized controlled trials of natural products compared with biologics in UC, irColitis, and related conditions, to further validate the clinical effectiveness of natural products.

The growing global burden of metabolic syndrome (MetS), a key driver of multiple chronic diseases, highlights the limited treatment options for its multifactorial pathophysiology. Tanshi-Tiaoti Decoction (TTD), a Chinese herbal formula comprised of Citri Reticulatae Pericarpium (Tangerine peel), Coicis Semen (Raw coix seed/Job’s tears), Raphani Semen (Radish seed), Nelumbinis Folium (Lotus leaf), Eckloniae/Laminariae thallus (Kelp), and Crataegi Fructus (Raw hawthorn fruit), demonstrates efficacy in the clinical management of MetS. However, its underlying molecular mechanisms remain incompletely elucidated. This study indicates that TTD restored gut microbiota homeostasis and bile acid (BA) profiles in high-fat diet (HFD)-induced MetS mice. TTD significantly attenuated body weight gain, fasting glucose levels, serum triglycerides, and hepatic steatosis. TTD corrected gut microbiota dysbiosis, most notably by reducing the Firmicutes/Bacteroidetes ratio. Fecal microbiota transplantation (FMT) validated the fact that the gut microbiome mediates TTD’s therapeutic effects. TTD regulated BA biosynthesis through this microbial modulation, and thus specifically increased hyodeoxycholic acid (HDCA). HDCA, which has been identified as the signature BA during TTD treatment, phenocopied TTD’s therapeutic effects against MetS by both activating the BA receptor TGR5 and subsequently promoting beige adipocyte browning. Collectively, TTD ameliorates MetS by reshaping microbial-mediated BA pools, and in particular elevates HDCA levels to thereby activate TGR5 and induce beige adipocyte browning. These findings support TTD as a promising herbal-based therapeutic strategy for the treatment of MetS.

Objective: To evaluate the comparative efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on glycaemic control, body weight, and lipid profile in adults with type 2 diabetes. Design: Systematic review and network meta-analysis. Data sources: PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase from database inception to 19 August 2023. Eligibility criteria for selecting studies: Eligible randomised controlled trials enrolled adults with type 2 diabetes who received GLP-1RA treatments and compared effects with placebo or any GLP-1RA drug, with a follow-up duration of at least 12 weeks. Trials with a crossover design, non-inferiority studies comparing GLP-1RA and other drug classes without a placebo group, using withdrawn drugs, and non-English studies were deemed ineligible. Results: 76 eligible trials involving 15 GLP-1RA drugs and 39 246 participants were included in this network meta-analysis; all subsequent estimates refer to the comparison with placebo. All 15 GLP-1RAs effectively lowered haemoglobin A _1c and fasting plasma glucose concentrations. Tirzepatide induced the largest reduction of haemoglobin A _1c concentrations (mean difference −2.10% (95% confidence interval −2.47% to −1.74%), surface under the cumulative ranking curve 94.2%; high confidence of evidence), and fasting plasma glucose concentrations (−3.12 mmol/L (−3.59 to −2.66), 97.2%; high confidence), and proved the most effective GLP-1RA drug for glycaemic control. Furthermore, GLP-1RAs were shown to have strong benefits to weight management for patients with type 2 diabetes. CagriSema (semaglutide with cagrilintide) resulted in the highest weight loss (mean difference −14.03 kg (95% confidence interval −17.05 to −11.00); high confidence of evidence), followed by tirzepatide (−8.47 kg (−9.68 to −7.26); high confidence). Semaglutide was effective in lowering the concentration of low density lipoprotein (−0.16 mmol/L (−0.30 to −0.02)) and total cholesterol (−0.48 mmol/L (−0.84 to −0.11)). Moreover, this study also raises awareness of gastrointestinal adverse events induced by GLP-1RAs, and concerns about safety are especially warranted for high dose administration. Conclusions: GLP-1RAs are efficacious in treating adults with type 2 diabetes. Compared with the placebo, tirzepatide was the most effective GLP-1RA drug for glycaemic control by reducing haemoglobin A _1c and fasting plasma glucose concentrations. GLP-1RAs also significantly improved weight management for type 2 diabetes, with CagriSema performing the best for weight loss. The results prompt safety concerns for GLP-1RAs, especially with high dose administration, regarding gastrointestinal adverse events. Systematic review registration: PROSPERO CRD42022342845.

Background: Inflammatory bowel disease (IBD) has caused severe health concerns worldwide. Studies on gut microbiota have provided new targets for preventing and treating IBD. Therefore, it is essential to have a comprehensive understanding of the current status and evolution of gut microbiota and IBD studies. Methods: A bibliometric analysis was performed on documents during 2003-2022 retrieved from the Scopus database, including bibliographical profiles, citation patterns, and collaboration details. Software programs of VOSviewer, CiteSpace, and the Bibliometrix R package visually displayed the mass data presented in the scientific landscapes and networks. Results: 10479 publications were retrieved, showing a steadily growing tendency in interest. Xavier Ramnik J. group led the total number of publications (73 papers) and 19787 citations, whose productive work aroused widespread concern. Among the 1977 academic journals, the most prolific ones were Inflammatory Bowel Diseases, Frontiers in Immunology, and Nutrients. Research outputs from the United States (US, 9196 publications), China (5587), and Italy (2305) were highly ranked.Conclusion: Our bibliometric study revealed that the role of gut microbiota has become a hot topic of IBD research worldwide. These findings are expected to improve understanding of research characteristics and to guide future directions in this field.