Cranial bone defect repair remains a significant challenge in craniomaxillofacial surgery， particularly when defects exceed the critical size defect （CSD） threshold， rendering them incapable of spontaneous healing without external intervention. Mechanical forces—including compression， tension， and shear stress—play a pivotal role in cranial development and regeneration. These forces regulate osteoblast differentiation and bone regeneration by activating key mechanotransduction pathways， such as the Wnt/β-catenin signaling pathway， the piezoelectric mechanosensitive ion channel Piezo1， and the transcriptional co-activators Yes-associated protein （Yes-Associated Protein，YAP） and Transcriptional co-activator with PDZ-binding motif （Transcriptional co-activator with PDZ-binding motif，TAZ）. Distinct types of mechanical forces exert specific effects on cellular behavior and the microenvironment. Clinically， applications such as Negative Pressure Wound Therapy （NPWT） have demonstrated efficacy in promoting angiogenesis-osteogenesis coupling， while tensile forces stimulate the dura mater to secrete osteogenic factors. Preliminary studies using artificial periosteum and other biomaterials have further validated that appropriate mechanical stimulation enhances bone repair. This review summarizes the effects of various mechanical forces and their associated signaling pathways on osteoblasts and their microenvironment， alongside an overview of current technological applications in this field.

Objective: To explore the effects of a classroom based transdiagnostic preventive intervention program for emotional disorders on depressive and anxiety symptoms, and resilience among junior high school students, so as to provide reference for promoting adolescent mental health. Methods: From October to December 2023, 72 students from a junior high school in Beijing were recruited as research subjects and divided into an intervention group ( n =36) and a control group ( n =36). The intervention group participated in 8 sessions (40 mins per session) of transdiagnostic prevention intervention course for emotional disorders; the control group students participated in research based learning lessons or class meetings. Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Resilience Scale-8 (RS-8) were used to evaluate junior high school students. The Wilcoxon signed rank test was used to compare the differences in depressive and anxiety symptoms, and resilience scores between the intervention group and the control group before and after the intervention. PROCESS macro was used to test the mediating effect. Results: There were no statistically significant differences in the scores of depressive and anxiety symptoms, and resilience before and after intervention in the intervention group ( Z =-1.07, 0.07, 1.43, all P >0.05). In the control group, the depressive symptoms score was higher after the intervention than before, and the resilience score was lower than before the intervention ( Z = 2.23 , -2.53, both P <0.05). After intervention, the depressive symptoms score in the intervention group was lower than that in the control group, and the resilience score in the intervention group was higher than that in the control group ( Z =-2.09, 3.33, both P < 0.05). The increase in the scores of resilience played a complete mediating role between the intervention and depressive symptoms, with the mediating effect value being -0.98 (95% CI =-2.47 to -0.11), accounting for 30.98% of the total effect. Conclusion Transdiagnostic preventive intervention program for emotional disorders based on classroom could prevent the deterioration of depressive symptom in junior high school students, and maintaining the level of resilience is an important factor for the intervention effect.

3CL protease (3CLpro) of SARS-CoV-2 is a pivotal enzyme required in coronavirus replication and transcription. Its highly conserved structure and the absence of homologous proteins in the host make it an ideal target for broad-spectrum anti-coronavirus drug development. In this work, we systematically investigated and compared the binding modes and dynamic properties of the four stereoisomers of a pyridyl-urea diyne ester (PyDU) molecule with two chiral centers within the 3CLpro active site. Through molecular docking, MD simulations, MM/GBSA binding free-energy calculations, and DCCM analysis, all four stereoisomers were stabilized primarily by hydrophobic packing. Among them, the (R,S) isomer exhibited the best overall performance, including docking score, binding free-energy components, and key residue interactions. The (R,S) and (S,R) isomers also enhanced the cooperative motions around the binding pocket, while the (R,S) isomer further modulated the flexibility of domain III, which may influence 3CLpro dimerization. Conversely, the (S,S) isomer exhibited the weakest affinity due to insufficient hydrophobic contact. By innovatively integrating chirality, binding energy and protein dynamical features, we revealed the dual role of chirality in modulating affinity and dynamic responses, which provides a theoretical basis for the chiral-guided design of coronavirus inhibitors.

Objective To explore the feasibility of magnetic compression technique (MCR) in the treatment of severe single mid-ureteral stricture in a rabbit model. Methods After 10 female New Zealand rabbits were selected, the distal end of the right ureter was ligated with silk thread. Two weeks after the operation, when the right ureter was dilated, the mid-ureter was ligated again with silk thread to create a severe single mid-ureteral stricture animal model. Longitudinal incisions were made at the upper and lower ends of the ligation site, and cylindrical NdFeB magnets with central holes (sub-magnets and main magnets) were placed to anastomose and recanalize the mid-ureteral stricture. The magnets were adjusted to the appropriate position to automatically align and attract each other. The longitudinal incision sites of the ureter were sutured with 6-0 Prolene thread, and the abdominal cavity was closed layer by layer. The operation time was recorded. X-ray films were taken every two days to confirm the position of the magnets and record the time of magnet detachment. Three weeks after the operation, the anastomotic specimens were obtained, and the formation of the anastomosis was evaluated with gross observation and histological staining. Results Two weeks after ligation, all experimental rabbits showed obvious dilation of the right ureter. The mid-ureteral ligation and placement of the male and female magnets were successfully completed in all 10 experimental rabbits, with an operation time of (24.00±5.15)minutes. The male and female magnets attracted each other well. X-ray examination showed that the magnets detached and entered the distal ureter (14.0±1.9) days after magnetic compression. The recanalization of the severe single mid-ureteral stricture was successfully achieved. The gross specimens and histological examination of the anastomosis showed that the anastomosis remained patent and the mucosal healing was good. All experimental rabbits survived well after the operation without serious complications. Conclusion MCT provides a new idea and novel method for the treatment of mid-ureteral stricture. This study confirmed the feasibility of this technique in treating severe single mid-ureteral stricture in a rabbit model. The operation is relatively simple and has potential for clinical application.

Objective To systematically evaluate the efficacy and safety of traditional Chinese medicine (TCM) compound in treating pulmonary nodules, providing evidence-based medical evidence for TCM intervention in pulmonary nodules. Methods Computer search of PubMed, CNKI, Wanfang, VIP, and SinoMed was conducted to select randomized controlled trials (RCTs) of TCM compound intervention in pulmonary nodules, with the retrieval time from the inception to November 29, 2023. The Cochrane bias risk assessment tool was used to evaluate the quality of the included studies, and Review Manager 5.4 was used for Meta-analysis. Results A total of 18 RCTs were included, covering 8 provinces across the country, with a total sample size of 1301 patients. The TCM compounds used in the included studies all incorporated the method of dissolving phlegm and dissipating nodules. There was a high risk of bias uncertainty in the included studies. Meta-analysis results suggested that TCM compound could significantly reduce the diameter of pulmonary nodules [MD=−1.41, 95%CI (−1.70, −1.13), P<0.001], decrease the number of nodules [MD=−0.37, 95%CI (−0.73, −0.01), P=0.05], alleviate clinical symptoms [MD=−4.84, 95%CI (−6.04, −3.64), P<0.001], and improve lung function [forced expiratory volume in one second (FEV1), MD=0.55, 95%CI (0.09, 1.01), P=0.02; FEV1/forced vital capacity, MD=6.12, 95%CI (4.47, 7.78), P<0.001]. However, there was no statistically significant difference in the probability of malignancy between the experimental group and the control group [MD=−0.01, 95%CI (−0.01, 0.00), P=0.09]. Conclusion TCM compound can significantly reduce the diameter of pulmonary nodules, decrease the number of nodules, alleviate clinical symptoms, and improve lung function, but future multicenter, large-sample, high-quality RCTs are still needed to further explore and verify this conclusion.

Esophageal cancer is a common malignancy with high incidence and poor prognosis. Conventional therapies fail to provide long-term benefits for patients, with postoperative recurrence and metastasis being the primary reasons for treatment failure. With the continuous development of nanomedicine, nanoparticle-based drug delivery has received widespread attention as a novel therapeutic approach. Among them, Fe3O4 magnetic nanoparticles have achieved a series of encouraging advancements in the treatment of esophageal cancer, owing to their unique superparamagnetism and biocompatibility. This paper provides a review of the relevant research on Fe3O4 magnetic nanoparticle-based drug delivery systems for the treatment of esophageal cancer.

ObjectiveTo investigate the preventive and therapeutic effects of Qingfei Paidu decoction (QFPDD) on acute lung injury (ALI) in mice and its underlying molecular mechanisms based on miRNA sequencing technology. MethodsTwenty-four 4-week-old male KM mice were randomly divided into a control group, a model group, and a QFPDD group (n = 8 per group). After one week of acclimatization, mice in the control and model groups were intragastrically administered ultrapure water (0.2 mL per dose), whereas mice in the QFPDD group were intragastrically administered QFPDD (1.6 g crude drug/mL, 0.2 mL per dose), twice daily for 8 consecutive days. On days 2–8, mice in the model and QFPDD groups were exposed to aerosolized lipopolysaccharide (LPS) solution (2.5 g/L, 4 mL per exposure) for 7 consecutive days. On day 9, blood was collected via the retro-orbital venous plexus under deep anesthesia, and lung tissues were harvested. Body weight and lung weight were measured, and the lung coefficient was calculated. Serum levels of inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were detected by ELISA. Lung histopathological changes were observed by HE staining of paraffin-embedded sections. miRNA expression profiles in lung tissues were analyzed using the Illumina HiSeq 2500 sequencing platform. Target genes of differentially expressed miRNAs were predicted using bioinformatics databases, and functional enrichment analysis of these target genes was performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Differentially expressed miRNAs were validated by reverse transcription quantitative real-time PCR (RT-qPCR). ResultsCompared with the control group, the model group showed a consistent body weight growth trend but a significantly increased lung coefficient (P < 0.01). ELISA results showed that serum levels of TNF-α and IL-6 were significantly elevated in the model group compared with the control group (P < 0.01), whereas QFPDD treatment significantly reduced serum TNF-α and IL-6 levels compared with the model group (P < 0.05). HE staining showed that, compared with the control group, the model group exhibited widened alveolar septa, massive inflammatory cell infiltration, partial alveolar expansion, and mild capillary dilation with congestion. In contrast, the QFPDD group showed only slightly widened alveolar septa and mild inflammatory cell infiltration compared with the model group. Intersection analysis of miRNA sequencing data identified 13 differentially expressed miRNAs common to both the model vs. control and QFPDD vs. model comparisons. Among them, 6 miRNAs (mmu-miR-203-3p, mmu-miR-181b-5p_R-1, hsa-miR-4286_R+1, mmu-miR-1843b-5p_L+1R-1_2, mmu-miR-22-3p, and mmu-miR-1964-3p) were significantly up-regulated in the model group (P < 0.05) and significantly down-regulated after QFPDD treatment (P < 0.05), showing a therapeutic reversal trend. GO analysis revealed that the target genes of the differentially expressed miRNAs were mainly enriched in biological processes such as RNA polymerase Ⅱ transcriptional regulation. KEGG analysis indicated that target genes were mainly enriched in signaling pathways including the mitogen-activated protein kinase (MAPK) pathway. RT-qPCR validation result for mmu-miR-203-3p was consistent with the sequencing analysis results. ConclusionQFPDD may exert preventive and therapeutic effects against ALI by regulating the expression of mmu-miR-203-3p and other miRNAs, thereby modulating inflammatory responses and the MAPK signaling pathway and participating in the pathological process of lung injury.

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.

Acute esophagogastric variceal bleeding （AEGVB） is one of the life-threatening complications of decompensated cirrhosis. Endoscopy is the main method for the diagnosis and treatment of AEGVB， and endoscopic treatment can effectively control acute bleeding and alleviate or eliminate varices. However， there is still a lack of consistent recommendations for the timing of endoscopic examination and intervention for AEGVB in related guidelines in China and globally. Existing studies in China and globally have low quality of evidence， with significant variations in the definition of “early endoscopy” and inconsistent conclusions. This article reviews the research advances in the timing of endoscopic treatment for AEGVB in liver cirrhosis， points out the controversies over the optimal timing of treatment， and discusses future research directions in this field.

ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.