Chronic pancreatitis （CP） is a common disease in clinical practice characterized by progressive inflammatory fibrosis of the pancreas. Gut microbiota， known as the “second genome” of humans， bidirectionally modulates the progression of fibrosis in CP via the gut-pancreas axis. This article systematically elaborates on the characteristics of gut microbiota during the progression of CP and its molecular mechanism in mediating pancreatic fibrosis through bacterial translocation， metabolites， immune regulatory networks， and microbe-pancreatic stellate cell interactions， with a focus on the pivotal role of short-chain fatty acids and inflammatory cytokine networks in pancreatic stellate cell activation and extracellular matrix deposition. In addition， this article explores the potential value of gut microbiota-targeted interventions in the prevention and treatment of CP fibrosis， such as probiotics， prebiotics， and fecal microbiota transplantation， and discusses the translational potential of using multi-omics technologies to identify diagnostic biomarkers and novel therapeutic targets for CP， in order to provide new ideas for the precise diagnosis and treatment of CP.

Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

Short-chain fatty acids （SCFA） are the main metabolic products generated by the fermentation of dietary fiber by gut microbiota. Studies have shown that SCFA not only play a role in energy metabolism， but also act as important signaling molecules， exhibiting a significant potential in alleviating liver and pancreatic fibrosis. The core mechanism of SCFA mainly involves the regulation of various key signaling pathways by activating G protein-coupled receptors and inhibiting the activity of histone deacetylase， thereby suppressing the activation and proliferation of hepatic stellate cell （HSC） and pancreatic stellate cell （PSC）， which is a key link in fibrosis formation. In addition， SCFA can effectively alleviate tissue inflammation response， improve intestinal barrier function， and regulate gut microbiota balance， thus indirectly preventing the process of fibrosis mediated by the “gut-liver/pancreas axis”. Compared with the research on SCFA in liver fibrosis， studies on their role in pancreatic fibrosis are limited. Given that HSC and PSC are highly homologous， the transcription factors and proteins that have been confirmed in liver fibrosis-related studies are also similarly expressed in PSC， suggesting that they may also influence the activation of PSC. This article systematically summarizes the recent advances in the research on SCFA in alleviating liver and pancreatic fibrosis， in order to provide new perspectives for exploring the mechanism of pancreatic fibrosis and developing related interventional strategies.

Objective To investigate the epidemiological characteristics and changing trend of typhus in Shaanxi Province from 2005 to 2023 to provide a scientific basis for its prevention and control. Methods Excel 2007, SPSS 25.0, Joinpoint 4.9.1.0, and Geoda 1.6 were used for data collection and statistical analysis. Super Map was used for data visualization to describe the changing characteristics of the disease. Results A total of 394 typhus cases were reported in Shaanxi Province from 2005 to 2023. The average annual incidence of typhus was 0.054/100 000, showing a dynamic fluctuation trend(AAPC=-3.3, t=-0.3, P>0.05). The cases were mainly concentrated in Baoji, Hanzhong and Xi′an, accounting for 78.68%. The incidence peak was from May to October, accounting for 64.21% of annual incidence. The epidemic season was from May to October and December. The incidence of the disease was concentrated in the 40-69 age group, accounting for 58.88%, and the sex was 1.07:1. The main occupation was farmers, accounting for 72.08%. The median time from onset to diagnosis was 7 days. Global spatial autocorrelation analysis showed that there were significant spatial autocorrelations in 11 years from 2005 to 2023(P<0.05). Local spatial autocorrelation analysis detected a total of 43“high-high”clustering areas, mainly concentrated in Baoji City. Conclusions The overall incidence of typhus in Shaanxi Province showed a dynamic fluctuation trend, with notable seasonal and regional aggregation. The incidence of typhus was higher in middle-aged and elderly people in rural areas. Surveillance should be strengthened in typhus endemic areas in summer and autumn, and health education should be conducted for key population to form good health habits and reduce the incidence of typhus.

ObjectiveTo explore the possible mechanism of action of Bushen Huoxue Granules （补肾活血颗粒， BHG） in the treatment of Parkinson's disease （PD） through the Nrf2/NLRP3 inflammasome axis. MethodsA total of 84 male C57/BL 6 mice were randomly divided into blank group， model group， Madopar group， dimethyl fumarate group， and low-， medium， and high-dose BHG group， with 12 mice in each group. Except for the blank group， all groups were induced into PD models by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine （MPTP） at a concentration of 30 mg/ml for 7 consecutive days. The blank group received an equal volume of saline. After model establishment， the low-， medium， and high-dose BHG groups were treated with 1.5， 3， and 6 g/（kg·d） of the BHG by gavage， respectively. The Madopar group was given 0.113 g/（kg·d） of Madopar tablets by gavage， and the dimethyl fumarate group was given 50 mg/（kg·d） of dimethyl fumarate solution. The blank group and the model group were given 10 ml/（kg·d） of distilled water by gavage. Gavage was administered once daily for 14 days. Behavioral changes were evaluated using the open field test （total distance， central area distance， and average speed）， rotarod test （time on the rod）， and climbing pole test （climbing time）. Serum levels of interleukin-1β （IL-1β）， interleukin-18 （IL-18）， and myeloperoxidase （MPO） were measured by ELISA. Immunohistochemistry was used to detect tyrosine hydroxylase （TH） expression in the brain substantia nigra. Immunofluorescence was used to detect α-synuclein （α-syn） expression. Western Blot was used to detect Nrf2， NLRP3， Caspase-1， and α-syn protein levels in the brain substantia nigra. RT-PCR was used to detect mRNA expression levels of Nrf2， NLRP3， and Caspase-1 in the brain substantia nigra. ResultsCompared with the blank group， the model group showed decreased total distance， central area distance， and average speed， reduced time on the rotarod， prolonged climbing time， reduced TH expression， increased α-syn expression， decreased Nrf2 protein and mRNA expression， increased NLRP3 and Caspase-1 protein and mRNA expression， and elevated serum IL-1β， IL-18， and MPO levels （P＜0.05）. Compared with the model group， all drug interventions significantly improved the above indicators （P＜0.05）. There was no significant differences in all indicators between the high-dose BHG group and the Madopar group （P＞0.05）. Compared with the dimethyl fumarate group， the medium and high-dose BHG groups showed increased Nrf2 mRNA expression in the brain substantia nigra （P＜0.05）. Compared with the high-dose BHG group， the low-dose group showed decreased total distance， central area distance， and average speed， reduced serum IL-18 levels， decreased α-syn， Nrf2， NLRP3， and Caspase-1 protein levels， and lower Nrf2 mRNA expression （P＜0.05）. ConclusionThe mechanism by which BHG treat PD may involve activating the Nrf2/NLRP3 inflammasome axis in the brain substantia nigra， thereby reducing neuroinflammation and α-syn aggregation. The high-dose group showed the best effects.

Lung cancer is the most common malignant tumor worldwide, ranking first in both incidence and mortality rates. According to the latest statistics from the International Agency for Research on Cancer (IARC), approximately 2.5 million new cases and around 1.8 million deaths from lung cancer occurred in 2022, placing a tremendous burden on global healthcare systems. The high mortality rate of lung cancer is closely linked to its subtle early symptoms, which often lead to diagnosis at advanced stages. This not only complicates treatment but also results in substantial economic losses. Current treatment options for lung cancer include surgery, radiotherapy, chemotherapy, targeted drug therapy, and immunotherapy. Among these, immunotherapy has emerged as the most groundbreaking advancement in recent years, owing to its unique antitumor mechanisms and impressive clinical benefits. Unlike traditional therapies such as radiotherapy and chemotherapy, immunotherapy activates or enhances the patient’s immune system to recognize and eliminate tumor cells. It offers advantages such as more durable therapeutic effects and relatively fewer toxic side effects. The main approaches to lung cancer immunotherapy include immune checkpoint inhibitors, tumor-specific antigen-targeted therapies, adoptive cell therapies, cancer vaccines, and oncolytic virus therapies. Among these, immune checkpoint inhibitors and tumor-specific antigen-targeted therapies have received approval from the U.S. Food and Drug Administration (FDA) for clinical use in lung cancer, significantly improving outcomes for patients with advanced non-small cell lung cancer. Although other immunotherapy strategies are still in clinical trials, they show great potential in improving treatment precision and efficacy. This article systematically reviews the latest research progress in lung cancer immunotherapy, including the development of novel immune checkpoint molecules, optimization of treatment strategies, identification of predictive biomarkers, and findings from recent clinical trials. It also discusses the current challenges in the field and outlines future directions, such as the development of next-generation immunotherapeutic agents, exploration of more effective combination regimens, and the establishment of precise efficacy prediction systems. The aim is to provide a valuable reference for the continued advancement of lung cancer immunotherapy.

Polysaccharide microneedle systems(PSMNs), as an emerging drug delivery technology, have demonstrated significant promise in recent years for treating corneal diseases. These systems overcome the limitations of traditional therapies, such as low bioavailability and poor patient compliance. This article systematically reviews the core research advances in PSMNs. First, microneedles are fabricated using natural polysaccharides like chitosan and hyaluronic acid, using precise manufacturing techniques such as mold casting and 3D printing. Second, drug release depends on microchannels formed by mechanical insertion of microneedles, enhancing drug permeation; moreover, chemically responsive materials are employed to control sustained-release kinetics. These materials synergize with the degradation mechanisms of polysaccharides to prolong the duration of therapeutic effect. Furthermore, PSMNs have been clinically applied for anti-inflammatory repair in dry eye disease, targeted antibacterial treatment of keratitis, and precise gene delivery. Research elucidates that PSMNs significantly enhance drug bioavailability by over ten-fold through a three-pronged mechanism involving efficient delivery, tissue repair, and immune regulation, while leveraging the inherent biocompatibility and biodegradability of polysaccharides to reduce side effects. This review provides a theoretical foundation for developing minimally invasive treatments for corneal diseases, propelling diagnostics and therapy towards more precise approaches.

BACKGROUND: Research has indicated that the disease burden of alopecia areata (AA) in China exceeds the global average. Therefore, accurate and updated epidemiological information is crucial for policymakers. In this study, we aimed to comprehensively assess the disease burden of AA in China. METHODS: The following four key indicators were utilized: the prevalence of cases; disability-adjusted life-years (DALYs); the age-standardized prevalence rate (ASPR); and the age-standardized DALY rate (ASDR) of AA according to the Global Burden of Disease (GBD) study 2021. We analyzed the epidemiological burden of AA in China during 2021, examined changes between 1990 and 2021, and performed a Bayesian age-period-cohort analysis to predict trends over the course of the next decade (2022-2030). Additionally, a Gaussian process regression model was applied to estimate the relationship between the gross domestic product (GDP) and the ASPR and ASDR of AA at the provincial level between 1992 and 2021. RESULTS: In 2021, the estimated number of patients with AA in China was approximately 3.49 million (95% uncertainty interval [UI], 3.37-3.62 million); of these patients, 1.20 million (95% UI, 1.16-1.25 million) were male and 2.29 million (95% UI, 2.20-2.37 million) were female. This large number of patients with AA resulted in a total of 114,431.25 DALYs (95% UI, 74,780.27-160,318.96 DALYs). Additionally, the ASPR and ASDR were 224.61 per 100,000 population (95% UI, 216.73-232.65 per 100,000 population) and 7.41 per 100,000 population (95% UI, 4.85-10.44 per 100,000 population), respectively; both of these rates were higher than the global averages. The most affected demographic groups were young and female individuals 25-39 years of age. Slight regional disparities were observed, with the northern and central regions of China bearing comparatively higher burdens. Between 1990 and 2021, the health loss and disease burden caused by AA in China remained relatively stable. The ASPR and ASDR of AA increased with the GDP when the annual GDP was less than 2 trillion Chinese yuan; however, a downward trend was observed as the GDP surpassed 2 trillion Chinese yuan. A slight upward trend in the disease burden of AA in China is predicted to occur over the next decade. CONCLUSIONS AA continues to be a public health concern in China that shows no signs of declining. Targeted efforts for young individuals and females are necessary because they experience a disproportionately high burden of AA.
Humans ; China/epidemiology* ; Alopecia Areata/epidemiology* ; Global Burden of Disease ; Female ; Male ; Adult ; Disability-Adjusted Life Years ; Middle Aged ; Prevalence ; Adolescent ; Young Adult ; Bayes Theorem ; Child ; Quality-Adjusted Life Years ; Child, Preschool

The aim of this study was to investigate the contribution of lung zinc ions to pathogenesis of lung ischemia/reperfusion (I/R) injury in rats. Male Sprague Dawley (SD) rats were randomly divided into control group, lung I/R group (I/R group), lung I/R + low-dose zinc chloride group (LZnCl₂+I/R group), lung I/R + high-dose ZnCl₂ group (HZnCl₂+I/R group), lung I/R + medium-dose ZnCl₂ group (MZnCl₂+I/R group) and TPEN+MZnCl₂+I/R group (n = 8 in each group). Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the concentration of zinc ions in lung tissue. The degree of lung tissue injury was analyzed by observing HE staining, alveolar damage index, lung wet/dry weight ratio and lung tissue gross changes. TUNEL staining was used to detect cellular apoptosis in lung tissue. Western blot and RT-qPCR were used to determine the protein expression levels of caspase-3 and ZIP8, as well as the mRNA expression levels of zinc transporters (ZIP, ZNT) in lung tissue. The mitochondrial membrane potential (MMP) of lung tissue was detected by JC-1 MMP detection kit. The results showed that, compared with the control group, the lung tissue damage, lung wet/dry weight ratio and alveolar damage index were significantly increased in the I/R group. And in the lung tissue, the concentration of Zn²⁺ was markedly decreased, while the cleaved caspase-3/caspase-3 ratio and apoptotic levels were significantly increased. The expression levels of ZIP8 mRNA and protein were down-regulated significantly, while the mRNA expression of other zinc transporters remained unchanged. There was also a significant decrease in MMP. Compared with the I/R group, both MZnCl₂+I/R group and HZnCl₂+I/R group exhibited significantly reduced lung tissue injury, lung wet/dry weight ratio and alveolar damage index, increased Zn²⁺ concentration, decreased ratio of cleaved caspase-3/caspase-3 and apoptosis, and up-regulated expression levels of ZIP8 mRNA and protein. In addition, the MMP was significantly increased in the lung tissue. Zn²⁺ chelating agent TPEN reversed the above-mentioned protective effects of medium-dose ZnCl₂ on the lung tissue in the I/R group. The aforementioned results suggest that exogenous administration of ZnCl₂ can improve lung I/R injury in rats.
Animals ; Reperfusion Injury/pathology* ; Male ; Rats, Sprague-Dawley ; Rats ; Chlorides/administration & dosage* ; Lung/pathology* ; Zinc Compounds/administration & dosage* ; Apoptosis/drug effects* ; Caspase 3/metabolism* ; Cation Transport Proteins/metabolism*