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.

Purpose: To evaluate the clinical outcomes of endovascular treatment for ruptured vertebral artery dissecting aneurysms (VADAs), with a focus on endovascular protocols tailored to different anatomical subtypes. Materials and Methods: We retrospectively analyzed 44 consecutive patients with ruptured VADAs treated from December 2014 to October 2024. Treatment strategies were guided by aneurysm location: parent artery occlusion (PAO) was used for lesions in non-dominant VAs, while stent-assisted coiling (SAC) reconstruction was used for aneurysms in dominant VAs. Patients were stratified by modified Rankin Scale (mRS) scores at 3-month follow-up (favorable: mRS 0–2; unfavorable: mRS 3–6). Results: All procedures were technically successful, including 12 single SAC, 13 overlapping SAC, and 19 with PAO (2 involving posterior inferior cerebellar artery preservation). Immediate complete occlusion was achieved in 50.0% of single SAC cases, 76.9% overlapping SAC, and 100% in the PAO group. Six (13.6%) procedure-related complications occurred, including 2 hemorrhagic and 4 ischemic events. Thirty patients (68.2%) had favorable outcomes, and the unfavorable outcomes group showed a higher incidence of ischemic events (P=0.012). An initial poor Hunt–Hess grade (≥IV) was an independent risk factor for unfavorable outcomes (odds ratio 6.35, 95% confidence interval 1.24–32.59; P=0.027). Angiographic follow-up was performed for 34 aneurysms, with complete occlusion achieved in 32 (94.1%); the remaining 2 patients were retreated. Conclusion Endovascular management is safe and effective for ruptured VADAs. Anatomical stratification—PAO for non-dominant VA lesions and SAC for dominant VA aneurysms—may help achieve favorable outcomes.

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.

Plant-derived exosome-like nanovesicles (PELNs), characterized by a natural lipid bilayer membrane, have rapidly emerged as a prominent research frontier in medicine owing to their unique biological properties and robust therapeutic potential. This review comprehensively examines the biological profiles, mechanistic functions, and recent engineering advancements of PELNs. In terms of composition, PELNs are uniquely enriched in plant-specific glycolipids, phosphatidylserine, secondary metabolites, and highly stable 2'-O-methylated miRNAs. This distinct molecular makeup endows them with exceptional biocompatibility, negligible immunogenicity, and the capacity for cross-species molecular communication. Mechanistically, PELNs demonstrate profound anti-inflammatory efficacy by suppressing the NF-κB and NLRP3 inflammasome pathways. They also serve as potent immune modulators, driving macrophage M1/M2 polarization and regulating T cell activity. Additionally, PELNs exhibit promising antitumor capabilities, targeting malignancies via reactive oxygen species (ROS) induction, TRAIL pathway activation, and tumor microenvironment remodeling. Crucially, the plant miRNAs encapsulated within PELNs remain highly stable in the gastrointestinal tract, allowing them to selectively alter gene expression in specific gut microbiota communities. This interaction deeply influences host immunity and metabolism, highlighting the vital role in cross-species regulation. Advancements in bioengineering have further expanded the clinical utility of PELNs. Targeted delivery efficiency can be significantly amplified via surface functionalization (e.g., folate and RGD sequences) and state-of-the-art drug loading technologies such as sonication and electroporation. Consequently, engineered PELNs surpass traditional synthetic nanocarriers in penetrating natural physiological barriers, particularly for oral and transdermal drug administration. Despite these advantages, clinical translation is currently hindered by the lack of standardized isolation protocols, challenges in scalable manufacturing, and the need for robust quality control frameworks. Looking forward, the integration of multi-omics approaches and AI-driven “molecular fingerprinting”—coupled with the design of synthetic biomimetic vesicles—will be instrumental in overcoming these bottlenecks, ultimately establishing PELNs as a next-generation platform for precision medicine and targeted nanotherapeutic delivery.

Objective To investigate the efficacy and safety of fiexible negative pressure suction sheath in the treatment of calyceal diverticulum stones, so as to provide reference for the diagnosis and treatment of this disease.Methods A retrospective analysis was conducted on 5 patients with simple calyceal diverticulum stones treated with flexible ureteroscopy plus fiexible negative pressure suction sheath in our hospital during Jan.2021 and Dec.2024.Data collected included general information, stone location, stone diameter, stone CT value, operation time, postoperative hemoglobin change, and stone free rate.Surgical efficacy and safety were evaluated.Results Among the 5 patients, 4 successfully underwent flexible ureteroscopic lithotripsy, while 1 converted to percutaneous nephrolithotomy due to inaccessible stone location.The median operation time was 120(95-150)min, and the median procalcitonin level was 0.089(0.076-0.112)ng/mL.There was no statistically significant difference in the hemoglobin level between preoperative and postoperative 24-hour measurements(P= 0.075).Abdominal CT scan on postoperative day 1 showed no residual stones, with Clavien grade I ureteral injury in 1 patient. No complications occurred during the 1-month follow-up after surgery.Conclusion Holmium laser lithotripsy under flexible ureteroscopy is one of the common surgical treatment for calyceal diverticulum stones.Combination with fiexible negative pressure suction sheath solves the problem of stone clearance during surgery, reduces the stone residual, demonstrates favorable safety, making flexible ureteroscopy an advantageous approach for treating calyceal diverticulum stones.

ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

BACKGROUND:Osteoporotic fracture is the most serious complication of osteoporosis.Previous studies have demonstrated that gut microbiota has a regulatory effect on skeletal tissue and that gut microbiota has an important relationship with osteoporotic fracture,but the causal relationship between the two is unclear. OBJECTIVE:To explore the causal relationship between gut microbiota and osteoporotic fractures using Mendelian randomization method. METHODS:The genome-wide association study(GWAS)datasets of gut microbiota and osteoporotic fracture were obtained from the IEU Open GWAS database and the Finnish database R9,respectively.Using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,Mendelian randomization analyses with random-effects inverse variance weighted,MR-Egger regression,weighted median,simple model,and weighted model methods were performed to assess whether there is a causal relationship between gut microbiota and osteoporotic fracture.Sensitivity analyses were performed to test the reliability and robustness of the results.Reverse Mendelian randomization analyses were performed to further validate the causal relationship identified in the forward Mendelian randomization analyses. RESULTS AND CONCLUSION:The results of this Mendelian randomization analysis indicated a causal relationship between gut microbiota and osteoporotic fracture.Elevated abundance of Actinomycetales[odds ratio(OR)=1.562,95%confidence interval(CI):1.027-2.375,P=0.037),Actinomycetaceae(OR=1.561,95%CI:1.027-2.374,P=0.037),Actinomyces(OR=1.544,95%CI:1.130-2.110,P=0.006),Butyricicoccus(OR=1.781,95%CI:1.194-2.657,P=0.005),Coprococcus 2(OR=1.550,95%CI:1.068-2.251,P=0.021),Family ⅩⅢ UCG-001(OR=1.473,95%CI:1.001-2.168,P=0.049),Methanobrevibacter(OR=1.274,95%CI:1.001-1.621,P=0.049),and Roseburia(OR=1.429,95%CI:1.015-2.013,P=0.041)would increase the risk of osteoporotic fractures in patients.Elevated abundance of Bacteroidia(OR=0.660,95%CI:0.455-0.959,P=0.029),Bacteroidales(OR=0.660,95%CI:0.455-0.959,P=0.029),Christensenellacea(OR=0.725,95%CI:0.529-0.995,P=0.047),Ruminococcaceae(OR=0.643,95%CI:0.443-0.933,P=0.020),Enterorhabdus(OR=0.558,95%CI:0.395-0.788,P=0.001),Eubacterium rectale group(OR=0.631,95%CI:0.435-0.916,P=0.016),Lachnospiraceae UCG008(OR=0.738,95%CI:0.546-0.998,P=0.048),and Ruminiclostridium 9(OR=0.492,95%CI:0.324-0.746,P=0.001)would reduce the risk of osteoporotic fractures in patients.We identified 16 gut microbiota associated with osteoporotic fracture by the Mendelian randomization method.That is,using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,eight gut microbiota showed positive causal associations with osteoporotic fracture and another eight gut microbiota showed negative causal associations with osteoporotic fracture.The results of this study not only identify new biomarkers for the early prediction of osteoporotic fracture and potential therapeutic targets in clinical practice,but also provide an experimental basis and theoretical basis for the study of improving the occurrence and prognosis of osteoporotic fracture through gut microbiota in bone tissue engineering.

OBJECTIVE: To analyze the clinical efficacy of manual reduction combined with 3D printing small splint external fixation and synchronous manual reduction combined with traditional small splint external fixation in the treatment of humeral shaft. METHODS: Between January 2021 and December 2022, 40 patients with humeral shaft fractures were treated with 3D printing small splints and traditional small splints. They were divided into 3D group and traditional group according to different fixation methods. Among them, there were 15 males and 5 females in the 3D group, aged from 20 to 52 years old with an average of (36.3±15.6) years old. In the traditional group there were 17 males and 3 females, aged from16 to 51 years old with an average of (32.9±17.2) years old. The occurrence of complications, duration of fracture healing, rate of fracture healing, subjective evaluation scores for brace comfort at 1 week and 4 weeks, as well as the Constant-Murley shoulder function score and Mayo elbow function score at 8 weeks and 16 weeks were compared between the two groups. RESULTS: All patients were followed up for 16 weeks. The 3D group did not experience any complications, while there were two cases of complications in the traditional group. However, this difference was not found to be statistically significant (χ²=2.105, P=0.146). The fracture healing time of the 3D group (90.1±4.5) days was significantly shorter compared to that of the traditional group (93.3±3.8) days (P<0.05). The subjective evaluation scores for brace comfort in the 3D group (53.7±2.3) points and (62.8±1.1) points were significantly higher than those in the traditional group (45.6±2.4) points and (52.3±1.4) points at 1 and 4 weeks after reduction (P<0.05). After 8 weeks of reduction, the Constant-Murley shoulder function score in the 3D group was(68.1±5.3) points, which demonstrated a statistically significant improvement compared to the traditional group(54.3±4.9) points (P<0.05). However, at 16 weeks post-reduction, there were no significant differences observed between the two groups (P>0.05). The Mayo elbow function score of the 3D group (84.1±7.5) points was significantly superior to that of the traditional group (79.5±6.8) points at 8 weeks post-reduction (P<0.05). However, there was no statistically significant difference between the two groups at 16 weeks post-reduction (P>0.05). CONCLUSION For humeral shaft fractures with conservative treatment indications, manual reduction combined with 3D printed small splints is a good choice for treatment. The patient's comfort level is higher, which can not only reduce the occurrence of complications, but also improve the fracture healing rate and joint function to a certain extent, and improve the patient's quality of life.
Humans ; Female ; Male ; Adult ; Middle Aged ; Humeral Fractures/physiopathology* ; Printing, Three-Dimensional ; Splints ; Adolescent ; Young Adult ; Fracture Healing

In recent years, the study of single-cell transcriptome sequencing technology in the heterogeneity of astrocytes (astrocytes) after spinal cord injury (SCI) has provided new perspectives on post-traumatic nerve regeneration and repair. To provide a review on the research progress of single-cell sequencing technology in astrocytes after spinal cord injury (SCI), and to more comprehensively and deeply elaborate the application of single-cell sequencing technology in the field of astrocytes after SCI. Single-cell sequencing technology can analyse the transcriptomes of individual cells in a high-throughput manner, thus revealing fine differences in cell types and states. By using single-cell sequencing technology, the heterogeneity of astrocytes after SCI and their association with nerve regeneration and repair were revealed. In conclusion, the application of single-cell sequencing technology provides an important tool to reveal the heterogeneity of astrocytes after SCI, to further explore the mechanisms of astrocytes in SCI, and to develop intervention strategies targeting their regulatory mechanisms in order to improve the therapeutic efficacy of SCI. The discovery of changes in astrocyte transcriptome dynamics has improved researchers' understanding of spinal cord injury lesion progression and provided new insights into the treatment of spinal cord injury at different time points. To date, all of these findings need to be validated by more basic research and sufficient clinical trials. In the future, single-cell sequencing technology, through interdisciplinary collaboration with bioinformatics, computer science, tissue engineering, and clinical medicine, is expected to open a new window for the treatment of spinal cord injury.
Spinal Cord Injuries/metabolism* ; Astrocytes/cytology* ; Single-Cell Analysis/methods* ; Humans ; Animals ; Transcriptome ; Nerve Regeneration

OBJECTIVE: To explore clinical efficacy of bone cement filling combined with lower extremity arterial balloon dilation in treating Wagner grade Ⅳ diabetic foot (DF). METHODS: From January to October 2024, 9 Wagner grade Ⅳ DF patients with lower extremity vascular occlusion were admitted, including 7 males and 2 females, aged from 51 to 87 years old;5 patients on the left side and 4 patients on the right side. All patients were underwent stageⅠdebridement of the affected foot and bone cement filling, and treated with lower extremity arterial balloon dilation after operation, they were. After the formation of the induced membrane, stageⅡwound repair was performed. The wound healing time and condition were observed. Ankle-brachial index (ABI) was used to evaluate the lower extremity vascular perfusion before operation and 3 months after operation, respectively. RESULTS: The wounds of all 9 patients healed completely, and the healing time ranged from 45 to 65 days. All patients were followed up for at least 6 months without recurrence. The skin of the affected foot wound healed with keratinization, and there was mild scar hyperplasia locally (1 patient had necrosis of the adjacent toe after stageⅠsurgery and was debridement and toe amputation again). The narrowed or occluded blood vessels of the lower extremities were all recanalized. ABI recovered from 0.3 to 0.5 before operation to 1.0 to 1.1 at 3 months after operation. CONCLUSION Bone cement filling combined with lower extremity arterial balloon dilation for the treatment of grade Wagner Ⅳ DF is conducive to promoting healing of the affected foot, effectively preventing secondary ulceration of the affected foot, and clinical therapeutic effect is satisfactory.
Humans ; Male ; Female ; Middle Aged ; Diabetic Foot/surgery* ; Aged ; Bone Cements/therapeutic use* ; Aged, 80 and over ; Lower Extremity/blood supply*