Despite of the widespread use of hydrogen and methane breath test, the variability in testing protocols, gas measurement techniques, and interpretation criteria continues to challenge the reproducibility and comparability across centers, especially in the Asia-Pacific region. The Asian Neurogastroenterology and Motility Association hence presents the first Asian monograph guiding application and interpretation of breath test. The monograph was formulated according to the framework of indications, preparatory process, performance, and interpretation of results, as well as future direction for research.

Background/Aims: Chronic constipation is prevalent yet under-diagnosed across Asia, compromising quality of life and burdening healthcare systems. Cultural stigma, varied diets, and limited access to standardized diagnostic tools delay timely care. Methods: The Bali Chronic Constipation Roundtable in November 2024, brought together experts from 11 Asian countries. The group reviewed epidemiological data, analyzed multinational questionnaire on clinical practice pattern, and conducted structured discussions to identify key barriers and propose region-specific recommendations. Results: Chronic constipation prevalence varies across Asia, ranging from 1.8% in India to 16.6% in Japan, with women and the elderly disproportionately affected. Under-reporting persists owing to cultural taboos and widespread self treatment with laxatives and traditional medications. Although the Rome IV criteria remains the global standard, they may not fully reflect Asian symptom profiles, and diagnosis is limited by scarce motility laboratories. First line therapies such as dietary-fiber optimization and osmotic laxatives are widely available, but newer pharmacotherapies (prucalopride, linaclotide, lubiprostone, and elobixibat) remain costly and unevenly accessible. Biofeedback for dyssynergic defecation is underutilized due to limited availability. Experts recommend expanded regional research on to refine diagnostic criteria, coupled with enhanced physician education and public awareness. They advocate accessibility to second-line and novel therapies that incorporate culturally attuned regional guidelines, and improved access to gastrointestinal motility testing. Conclusions The Bali Chronic Constipation Roundtable highlighted Asia’s need for region specific diagnostics and management. Addressing diagnostic and treatment gaps will improve outcomes, while ongoing researcher clinician policy collaboration must standardize guidelines, advance research, and ensure equitable care across Asia.

Xuanbi Xuanfuhua Decoction(XBXFHD), as an empirical formula developed by Professor Xie Sheng, a National Qihuang Scholar, for the treatment of critical and severe respiratory diseases, has demonstrated definite efficacy in pulmonary sepsis, but its mechanism of action requires further investigation. This study explores the intervention effect of XBXFHD on pulmonary sepsis in rats from the perspective of regulating PANapoptosis. A rat model of pulmonary sepsis was successfully established by combined intratracheal injection of lipopolysaccharide (LPS), Staphylococcus aureus, and Escherichia coli, with control and different dosage drug groups established. HE staining, ELISA, Western blot, and flow cytometry were used to evaluate pathological changes in lung tissue, levels of inflammatory factors, cell apoptosis, expression of pan-apoptosis-related proteins (such as Caspase-3, Bcl-2, ZBP1, RIPK1, RIPK3, MLKL), and the proportion of CD4+ T cell subsets (Th17 and Treg). The results showed that XBXFHD significantly reduced alveolar inflammatory infiltration, congestion, and lung injury scores (P < 0.05), decreased the wet-to-dry weight ratio of the lungs, and reduced protein exudation in BALF. At the same time, XBXFHD inhibited the expression of Caspase-3, upregulated the expression level of Bcl-2 (P < 0.01), significantly reduced the apoptosis rate (P < 0.01), and downregulated the mRNA and protein levels of pan-apoptosis-related proteins (high-dose drug group P < 0.01). In addition, the formula reduced the proportion of Th17 (P < 0.01), increased the proportion of Treg (P < 0.05), downregulated the levels of pro-inflammatory factors (such as IL-18, IL-1β, TNF-α), and upregulated the levels of anti-inflammatory factors (such as IL-4, IL-10) (P < 0.05). The drug's effects were dose-dependent. These results indicate that XBXFHD improves pulmonary sepsis-related lung injury by inhibiting PANapoptosis-related proteins, regulating the Th17/Treg immune balance, and reducing inflammatory responses, with dose-dependent effects, providing experimental evidence for the clinical application of this formula.

OBJECTIVES: Sepsis-associated acute lung injury (S-ALI) is one of the major causes of death in intensive care unit (ICU) patients, yet its mechanisms remain incompletely understood and effective therapies are lacking. Lytic cell death of macrophages is a key driver of the inflammatory cascade in S-ALI. PANoptosis, a newly recognized form of lytic cell death characterized by PANoptosome assembly and activation, involves plasma membrane rupture (PMR) mediated by ninjurin-1 (NINJ1), a recently identified pore-forming protein. Itaconic acid is known for its anti-inflammatory effects, but its role in macrophage PANoptosis during S-ALI is unclear. This study aims to investigate the protective effect of itaconic acid on macrophage PANoptosis in S-ALI to provide new therapeutic insights. METHODS: Male specific-pathogen-free C57BL/6J mice (6-8 weeks, 18-20 g) received intraperitoneal lipopolysaccharide (LPS) to establish a classical S-ALI model. Western blotting was used to assess PANoptosome-related proteins and enzymes involved in the itaconic acid metabolic pathway, while real-time reverse transcription polymerase chain reaction and metabolomics quantified itaconic acid levels. Primary peritoneal macrophages (PMs) were pretreated with the itaconate derivative 4-octyl itaconate (4-OI) and then exposed to tumor necrosis factor alpha (TNF-α) plus interferon gamma (IFN-γ) to induce PANoptosis. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Western blotting was employed to quantify enzymes of the itaconate-metabolic pathway in PANoptotic macrophages, to evaluate the impact of 4-OI on PANoptosome-associated proteins, and to determine NINJ1 abundance in lung tissues from S-ALI mice and in PANoptotic macrophages. Fluorescent dye FM_4-64 was used to visualize 4-OI-mediated changes in PMR, whereas immunofluorescence staining mapped the effect of 4-OI on both the expression level and membrane localization of NINJ1 in PANoptotic macrophages. The effect of 4-OI on lactate dehydrogenase (LDH) release in culture supernatants and peripheal blood serum was assessed using a LDH assay kit, and non-denataring polyacylamide gel electrophoresis was used to assess the expression of NINJ1 in S-ALI mouse lung tissues and the impact of 4-OI on the expression of PANoptosis-associated NINJ1 multimeric reflected protein in macropahges. RESULTS: In S-ALI mouse lungs, PANoptosome components [NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Gasdermin D (GSDMD), Caspase-1, Z-DNA binding protein (ZBP1), and Caspase-3] and phosphorylated mixed lineage kinase domain-like protein (MLKL) S345 were significantly upregulated (all P<0.05), while metabolomics showed compensatory increases in itaconic acid and its key enzymes [aconitate decarboxylase 1 (ACOD1)/immunoresponsive gene 1 (IRG1)]. In macrophages, 4-OI obviously suppressed PANoptosome protein expression, reduced LDH release, restored plasma membrane integrity, and inhibited NINJ1 expression and oligomerization at the membrane (P<0.05). CONCLUSIONS Itaconic acid may alleviate macrophage PANoptosis in S-ALI by inhibiting NINJ1-mediated plasma membrane rupture. Targeting NINJ1 or enhancing itaconate pathways may offer a novel therapeutic strategy for S-ALI.
Animals ; Acute Lung Injury/pathology* ; Succinates/pharmacology* ; Sepsis/complications* ; Mice, Inbred C57BL ; Male ; Mice ; Macrophages/pathology* ; Cell Membrane/metabolism* ; Lipopolysaccharides ; Hydro-Lyases

The probability of pulmonary infection in stroke patients with dysphagia will be multiplied,which may endanger the life of the patients,and is a major problem to be solved urgently in clinic.Stroke and dysphagia can both lead to intestinal flora disorders,destroy the intestinal barrier function and create the con-ditions for the migration of opportunistic pathogenic bacteria from the intestinal tract to the lungs,which may trigger or exacerbate the symptoms of pulmonary infections in the patients.Based on the theory of"microbe-gut-lung"axis,this article reviews the related studies on the disorder of intestinal flora caused by dietary chan-ges after stroke and dysphagia,and then leads to the migration of intestinal flora to the lungs,resulting in pul-monary infections,as well as the potential impact of aspiration on the pulmonary infections complicating dys-phagia after stroke.The potential impact of aspiration on post-stroke swallowing disorders and concomitant lung infections.In order to explore the potential mechanism of recurrent pulmonary infections in the patients with post-stroke dysphagia from the perspective of parenteral dissemination of intestinal flora,and to provide new ideas for subsequent clinical interventions.

Chikungunya fever is spreading continuously worldwide，posing a growing public health challenge alongside other arboviral diseases. This article systematically reviews the epidemiological characteristics of chikungunya fever，analyzes the pandemic potential of Aedes mosquito-borne diseases and discusses integrated prevention and control strategies for China in the context of increasing importation risk，drawing on containment practices from multiple countries and regions.

Objective To investigate the ameliorative effects of 4-hydroxybenzyl alcohol(4HBA)on energy metabolism in ischemic astrocytes(ASC).Methods Primary ASC were isolated from rat cortical tissue,and then randomly divided into control,oxygen-glucose deprivation/reoxygenation(OGD/R)group,low-,medium-and high-dose 4HBA groups(50,100 and 200 μmol/L),and edaravone group.Except for the control group,OGD/R injury models were established in a tri-gas incubator.The following parameters were measured:cell mortality,adenosine triphosphate(ATP)content,activities of mitochondrial ATP enzymes(Na+/K+-ATPase and Ca2+/Mg2+-ATPase),activities of mitochondrial complexes Ⅰ-Ⅴ,and expression of energy metabolism-related genes.Results Compared with the control group,the OGD/R group showed significantly higher cell mortality[(9.49±0.85)％vs(0.00±0.00)％,P＜0.01],along with obviously decreased ATP content,Na+/K+-ATPase activity,Ca2+/Mg2+-ATPase activity,and mitochondrial complex Ⅰ-V activities(P＜0.01).Compared with the OGD/R group,three 4HBA groups as well as the edaravone group exhibited significantly reduced cell mortality and elevated ATP content,Na+/K+-ATPase activity,and complex Ⅰ,Ⅲ,and V activities.The high-and medium-dose 4HBA groups and the edaravone group demonstrated increased Ca2+/Mg2+-ATPase activity,and the high-dose 4HBA group and edaravone group exhibited more enhanced complexⅡ activity,and the three 4HBA groups had elevated complex Ⅳ activity(P＜0.05,P＜0.01).Conclusion 4HBA exerts protective effect against ischemic injury in ASC by mitigating energy metabolism dysfunction and reducing cell death.

Chikungunya fever is spreading continuously worldwide，posing a growing public health challenge alongside other arboviral diseases. This article systematically reviews the epidemiological characteristics of chikungunya fever，analyzes the pandemic potential of Aedes mosquito-borne diseases and discusses integrated prevention and control strategies for China in the context of increasing importation risk，drawing on containment practices from multiple countries and regions.

Objective To investigate the ameliorative effects of 4-hydroxybenzyl alcohol(4HBA)on energy metabolism in ischemic astrocytes(ASC).Methods Primary ASC were isolated from rat cortical tissue,and then randomly divided into control,oxygen-glucose deprivation/reoxygenation(OGD/R)group,low-,medium-and high-dose 4HBA groups(50,100 and 200 μmol/L),and edaravone group.Except for the control group,OGD/R injury models were established in a tri-gas incubator.The following parameters were measured:cell mortality,adenosine triphosphate(ATP)content,activities of mitochondrial ATP enzymes(Na+/K+-ATPase and Ca2+/Mg2+-ATPase),activities of mitochondrial complexes Ⅰ-Ⅴ,and expression of energy metabolism-related genes.Results Compared with the control group,the OGD/R group showed significantly higher cell mortality[(9.49±0.85)％vs(0.00±0.00)％,P＜0.01],along with obviously decreased ATP content,Na+/K+-ATPase activity,Ca2+/Mg2+-ATPase activity,and mitochondrial complex Ⅰ-V activities(P＜0.01).Compared with the OGD/R group,three 4HBA groups as well as the edaravone group exhibited significantly reduced cell mortality and elevated ATP content,Na+/K+-ATPase activity,and complex Ⅰ,Ⅲ,and V activities.The high-and medium-dose 4HBA groups and the edaravone group demonstrated increased Ca2+/Mg2+-ATPase activity,and the high-dose 4HBA group and edaravone group exhibited more enhanced complexⅡ activity,and the three 4HBA groups had elevated complex Ⅳ activity(P＜0.05,P＜0.01).Conclusion 4HBA exerts protective effect against ischemic injury in ASC by mitigating energy metabolism dysfunction and reducing cell death.

Objective: To investigate protective effects of nicotinamide mononucleotide (NMN) on ethanol-induced DNA damage in L02 cells, so as to provide the evidence for adjuvant therapy of NMN on alcoholic liver diseases. Methods: L02 cells were pretreated with different concentrations of NMN (0, 1, 2, 4 and 8 mmol/L) for 6 h, and then were exposed to 0.4% ethanol for 12 h. The treated cells were divided into the control group, 0.4% ethanol group and different concentrations of NMN groups. Cell viability was analyzed using trypan blue staining for determining the concentration of NMN as a protective agent. The effects of NMN on ethanol-induced DNA damage in L02 cells were evaluated using immunofluorescence detection and reactive oxygen species (ROS) assay. L02 cells were exposed to 0.4% ethanol for 12 h, cultured in a medium containing a protective concentration of NMN, and divided into PBS group and NMN group. Cell viability was detected at 0, 2, 4, 8, 16 and 32 h, and the effects of NMN on repairing ethanol-induced DNA damage were evaluated by alkaline comet assay. Results: The cell viability was lower in 0.4% ethanol group than than in the control group, and was higher in different concentrations of NMN groups than in 0.4% ethanol group (all P<0.05), with no significant difference in the cells viability between 4 mmol/L and higher concentrations of NMN groups and the control group (all P>0.05). Therefore, 4 mmol/L NMN was selected as a protective agent. The cell tail moments, relative immunofluorescence intensities of γH2AX and relative levels of ROS were higher in 0.4% ethanol group than in the control group, and lower in 4 mmol/L and higher concentrations of NMN groups than in 0.4% ethanol group (all P<0.05). The cell viability was increased and the cell tail moment was shortened with the increase of 4 mmol/L NMN intervention time; and the cell viability in 4 h and more of NMN groups were higher, and the cell tail moment were lower than that in PBS group (all P<0.05). Conclusions NMN attenuates DNA damage in a dose-dependent manner and promotes the repair of DNA damage in a time-dependent manner. NMN has a protective effect on ethanol-induced DNA damage in hepatocytes.