Intrahepatic cholangiocarcinoma (ICC) is a highly malignant primary tumor originating from the intrahepatic bile duct epithelium. Current clinical consensus emphasizes that early detection,timely diagnosis,and R0 resection (when feasible) are critical strategies for improving outcomes. Advances in surgical techniques and multidisciplinary approaches have facilitated precision medicine-guided systemic therapies,including adjuvant and neoadjuvant regimens. These interventions significantly delay postoperative recurrence and improve 5-year survival rates. Systemic treatments have also modestly enhanced prognoses for advanced ICC patients. Artificial intelligence-driven radiomics and deep learning technologies show substantial efficacy in ICC diagnosis,prognostic assessment,and lymph node metastasis prediction,advancing precision medicine applications. Despite these therapeutic advances,survival outcomes-particularly for advanced-stage ICC-remain suboptimal. Future efforts should prioritize molecular signature-guided therapies,novel combination regimens,and artificial intelligence-assisted comprehensive management to establish a molecularly driven precision treatment framework.

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant primary tumor originating from the intrahepatic bile duct epithelium. Current clinical consensus emphasizes that early detection,timely diagnosis,and R0 resection (when feasible) are critical strategies for improving outcomes. Advances in surgical techniques and multidisciplinary approaches have facilitated precision medicine-guided systemic therapies,including adjuvant and neoadjuvant regimens. These interventions significantly delay postoperative recurrence and improve 5-year survival rates. Systemic treatments have also modestly enhanced prognoses for advanced ICC patients. Artificial intelligence-driven radiomics and deep learning technologies show substantial efficacy in ICC diagnosis,prognostic assessment,and lymph node metastasis prediction,advancing precision medicine applications. Despite these therapeutic advances,survival outcomes-particularly for advanced-stage ICC-remain suboptimal. Future efforts should prioritize molecular signature-guided therapies,novel combination regimens,and artificial intelligence-assisted comprehensive management to establish a molecularly driven precision treatment framework.

Flap transplantation is a critical surgical strategy for the reconstruction of tissue defects caused by trauma, tumor resection, and congenital malformations, and its survival rate directly determines surgical efficacy and patient prognosis. Following transplantation, flaps inevitably undergo ischemia-reperfusion (I/R) injury, during which oxidative stress, inflammatory responses, and metabolic disturbances are intricately intertwined, ultimately leading to cellular injury and tissue necrosis. Recent studies have demonstrated that multiple forms of programmed cell death—including apoptosis, pyroptosis, ferroptosis, necroptosis, and PANoptosis—play central roles in flap I/R injury. The extensive crosstalk and molecular interactions among these pathways form a highly complex cell death network. Specifically, apoptosis is mediated by the imbalance of Bcl-2 family proteins and the activation of cysteine-dependent aspartate-specific protease (caspase) cascades; pyroptosis is driven by the NLRP3-caspase-1-GSDMD axis, resulting in membrane pore formation and the release of pro-inflammatory cytokines; ferroptosis is characterized by iron-dependent lipid peroxidation and dysfunction of glutathione peroxidase 4 (GPX4); necroptosis is triggered by the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-RIPK3-MLKL signaling complex, leading to membrane rupture; and PANoptosis represents an integrated form of inflammatory cell death that coordinates multiple death pathways. Importantly, these forms of programmed cell death are not independent but are interconnected through extensive signaling crosstalk. Key regulatory molecules, including caspase-8, reactive oxygen species (ROS), nuclear factor-κB (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2), collectively modulate the dynamic balance among these pathways. Therefore, the multidimensional interplay and spatiotemporal dynamics of programmed cell death constitute a fundamental pathological basis of flap I/R injury. This review systematically summarizes the latest advances in the mechanisms and interactions of various programmed cell death pathways in flap I/R injury, aiming to elucidate the underlying regulatory network. These insights may provide novel theoretical foundations for optimizing flap protection strategies, improving flap survival, and promoting tissue repair.

Background: According to the World Health Organization (WHO), 6.7 million people die annually due to air pollution caused by solid fuel use, with the majority of deaths resulting from respiratory diseases and cardiovascular conditions. In Mongolia, air pollution ranks as the fourth leading risk factor contributing to mortality, following hypertension, diabetes, and other major health risks. Although there have been numerous studies on outdoor air pollution in Mongolia, research linking indoor air pollution at the household level with the health status of residents remains limited. Aim: To compare indoor PM2.5 concentrations in households of Ulaanbaatar and Darkhan and examine their association with hypertension during the winter season. Materials and Methods: The study was conducted during November and December 2023, and January 2024, involving 240 households in Ulaanbaatar and Darkhan. Indoor PM2.5 concentrations were measured using Purple Air real-time sensors continuously for 24 hours over approximately one month. After measuring indoor air pollution, individuals aged 18–60 years living in the selected households were recruited based on specific inclusion criteria. Blood pressure was measured three times and the average value was recorded. Information on respiratory illnesses was collected through structured questionnaires. Statistical analysis was performed using STATA version 19.0. Results: A total of 241 households participated in the study, with 116 from Ulaanbaatar and 125 from Darkhan. Of the participants, 46.5% were male and 53.5% were female. In terms of housing type, 96 households (39.8%) lived in gers, 97 (40.2%) lived in stove-heated houses, and 48 (19.9%) lived in apartments. Among all participants, 66.0% (n=159) had hypertension and 34.0% (n=79) had normal blood pressure. Among participants aged over 40, 69.9–88.5% had hypertension, which is statistically significantly higher compared to younger individuals (p=0.0001). By body mass index, 75.3% (n=72) of overweight individuals and 78.4% (n=58) of obese participants had hypertension, showing a statistically significant difference compared to participants with normal weight (p=0.0001). The 24-hour average concentration of indoor PM2.5 was measured using the Purple Air device, and the levels in gers and stove-heated houses exceeded the limit set by the MNS 4585:2025 standard (37.5 µg/m³) Conclusion This study identified a relationship between environmental factors, such as air pollution and housing type, and the prevalence of hypertension. The indoor PM2.5 concentration in gers and stove-heated houses was above the standard limit, indicating a negative impact on the health of those residents. Furthermore, the high prevalence of hypertension among participants over the age of 40 and those who are overweight suggests a possible link to lifestyle and environmental conditions.

Background: Particulate matter with an aerodynamic diameter of 2.5 micrometers or smaller (PM2.5) penetrates deep into the alveoli through the respiratory tract and is characterized by its ability to induce oxidative stress, systemic inflammation, and vascular inflammation. Mongolia ranks among the countries with the highest levels of air pollution. In Ulaanbaatar, where more than half of the country’s population resides, wintertime PM2.5 concentrations often exceed 200 μg/m³, which is about eight times higher than the World Health Organization (WHO) guideline value. A study involving 1,200 adults in Ulaanbaatar showed that quality of life deteriorated sharply during periods of high air pollution, with effects more pronounced among individuals who already had impaired respiratory function. Aim: To examine the relationship between indoor household PM2.5 concentrations and lung function indicators among adults in Ulaanbaatar and Darkhan. Materials and Methods: This analytical cross-sectional study recruited adult participants from Ulaanbaatar and Darkhan through targeted sampling. Household air quality was measured using PurpleAir sensors, which were installed in participants’ homes for one month. After exposure measurement, lung function was assessed via spirometry. Statistical analyses were conducted using SPSS version 25.0. Results: A total of 236 participants were included: 114 (48.3%) from Ulaanbaatar and 122 (51.7%) from Darkhan. The sample consisted of 111 men (47.0%) and 125 women (53.0%). The mean indoor PM2.5 concentration was 66.24 μg/m³ (SD 44.87 μg/m³), ranging from a minimum of 7.79 μg/m³ to a maximum of 264.55 μg/m³. Stratification by housing type showed the highest PM2.5 levels in gers (82.34 μg/m³), followed by detached houses (67.34 μg/m³), while apartments had the lowest concentrations (32.24 μg/m³). Correlation analysis revealed statistically significant negative associations between PM2.5 levels and measures of expiratory function, including the FEV1/FVC ratio, peak expiratory flow (PEF), and mid-expiratory flow (FEF25–75). Reduced forced vital capacity (FVC) was observed in 9.4% of participants, reduced forced expiratory volume in one second (FEV1) in 15.3%, and a decreased FEV1/FVC ratio in 3.8%. Conclusion Indoor household PM2.5 concentrations were highest in gers, and expiratory flow-related lung function parameters showed significant negative associations with particulate exposure. This suggests that indoor PM2.5 primarily affects airflow limitation rather than overall lung volumes in this population.

BACKGROUND: The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system. METHODS: This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China. RESULTS: At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained. CONCLUSION: In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system. TRIAL REGISTRATION ClinicalTrials.gov , NCT03656848.
Humans ; Cost-Benefit Analysis ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Angiography/methods* ; Middle Aged ; Aged ; Coronary Artery Disease/surgery* ; Quality-Adjusted Life Years ; Fractional Flow Reserve, Myocardial/physiology*

Stearoyl-coenzyme A desaturase 1 (SCD1) catalyzes the rate-limiting step of de novo lipogenesis and modulates lipid homeostasis. Although numerous SCD1 inhibitors were tested for treating metabolic disorders both in preclinical and clinic studies, the tissue-specific roles of SCD1 in modulating obesity-associated metabolic disorders and determining the pharmacological effect of chemical SCD1 inhibition remain unclear. Here a novel role for intestinal SCD1 in obesity-associated metabolic disorders was uncovered. Intestinal SCD1 was found to be induced during obesity progression both in humans and mice. Intestine-specific, but not liver-specific, SCD1 deficiency reduced obesity and hepatic steatosis. A939572, an SCD1-specific inhibitor, ameliorated obesity and hepatic steatosis dependent on intestinal, but not hepatic, SCD1. Mechanistically, intestinal SCD1 deficiency impeded obesity-induced oxidative stress through its novel function of inducing metallothionein 1 in intestinal epithelial cells. These results suggest that intestinal SCD1 could be a viable target that underlies the pharmacological effect of chemical SCD1 inhibition in the treatment of obesity-associated metabolic disorders.

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

Xerostomia (dry mouth) is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren's syndrome, with no permanent cure existing for this debilitating condition. To this end, in vitro platforms are needed to test therapies directed at salivary (fluid-secreting) cells. However, since these are highly differentiated secretory cells, the maintenance of their differentiated state while expanding in numbers is challenging. In this study, the efficiency of three reversible thermo-ionically crosslinked gels: (1) alginate-gelatin (AG), (2) collagen-containing AG (AGC), and (3) hyaluronic acid-containing AG (AGHA), to recapitulate a native-like environment for human salivary gland (SG) cell expansion and 3D spheroid formation was compared. Although all gels were of mechanical properties comparable to human SG tissue (~11 kPa) and promoted the formation of 3D spheroids, AGHA gels produced larger (>100 cells/spheroid), viable (>93%), proliferative, and well-organized 3D SG spheroids while spatially and temporally maintaining the high expression of key SG proteins (aquaporin-5, NKCC1, ZO-1, α-amylase) for 14 days in culture. Moreover, the spheroids responded to agonist-induced stimulation by increasing α-amylase secretory granules. Here, we propose alternative low-cost, reproducible, and reversible AG-based 3D hydrogels that allow the facile and rapid retrieval of intact, highly viable 3D-SG spheroids.
Humans ; Hydrogels/chemistry* ; Acinar Cells/cytology* ; Spheroids, Cellular/cytology* ; Salivary Glands/cytology* ; Gelatin/chemistry* ; Collagen/chemistry* ; Alginates/chemistry* ; Cell Culture Techniques/methods* ; Hyaluronic Acid/chemistry* ; Cell Proliferation ; Cell Survival ; Cells, Cultured

Objective: The variety and efficacy of biomarkers available that may be used objectively to diagnose major depressive disorder (MDD) in adults are unclear. This systematic review aims to identify and evaluate the variety of objective markers used to diagnose MDD in adults. Methods: The search strategy was applied via PubMed and PsycINFO over the past 10 years (2013–2023) to capture the latest available evidence supporting the use of biomarkers to diagnose MDD. Data was reported through narrative synthesis. Results: Forty-two studies were included in the review. Findings were synthesised based on the following measures: blood, neuroimagingeurophysiology, urine, dermatological, auditory, vocal, cerebrospinal fluid and combinatory—and evaluated based on its sensitivity/specificity and area under the curve values. The best predictors of blood (MYT1 gene), neuroimagingeurophysiological (5-HT1A auto-receptor binding in the dorsal and median raphe), urinary (combined albumin, AMBP, HSPB, APOA1), cerebrospinal fluid-based (neuron specific enolase, microRNA) biomarkers were found to be closely linked to the pathophysiology of MDD. Conclusion A large variety of biomarkers were available to diagnose MDD, with the best performing biomarkers intrinsically related to the pathophysiology of MDD. Potential for future research lies in investigating the joint sensitivity of the best performing biomarkers identified via machine learning methods and establishing the causal effect between these biomarkers and MDD.