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.

Since Li Dongyuan formally proposed the concept of "wind medicinals" （Feng Yao），their clinical application has been highly valued by physicians throughout history. However，influenced by the evolution of the term and connotation of "wind medicinals" in modern times，its conceptual understanding，leading to a decline in clinical utilization. Since the new century，Professor Wang Mingjie has integrated LIU Wanxu's sweat pore （Xuanfu） theory into the reinterpretation of wind medicinals，proposing the "Xuanfu-dredging wind medicinal theory"， which has gained widespread recognition in academic circles，revitalizing their clinical application. This study traces the origin of the Xuan-dredging wind medicinals theory and reviews their current functions and clinical applications，finding that the theoretical framework is preliminarily established. Characterized by their pungent and dispersing properties，wind medicines act by opening the Xuanfu throughout the body，exerting therapeutic effects such as dispelling pathogens，resolving stagnation，and enhancing treatments like blood-activation，spleen-fortification，and heat-clearing. They are widely used，showing advantages in treating systemic diseases including ophthalmic and cardiovascular/cerebrovascular disorders. Modern pharmacological research indicates preliminary consensus on hypotheses of cerebral，intestinal，hepatic，and renal Xuanfu. studies on formulas （e.g.，Qufeng Tongqiao Fang），single herbs （e.g.，Mahuang and Gegen），and active constituents （e.g.，tetramethylpyrazine） provide evidence that wind medicines improve key mechanisms like blood-brain barrier function and cerebral microcirculation （material basis of cerebral Xuanfu），supporting their use in brain disorders （e.g.，cerebral ischemia，depression）. Despite clinical and pharmacological support，the clinical application system for wind medicines remains incomplete. Future efforts should focus on high-quality clinical research and mechanistic studies to establish personalized application systems，enhance Xuanfu opening practices，and ensure the effectiveness and safety of wind medicines.

Lipoatrophic diabetes(LD) is a rare and distinct form of diabetes characterized by notable clinical heterogeneity. It is often considered one of the manifestations of lipodystrophy syndrome(LDS). In clinical practice, LD is frequently misdiagnosed as type 2 diabetes; however, its management protocols and prognostic outcomes differ significantly from those of other diabetes subtypes. Therefore, timely and accurate diagnosis is of great clinical importance. This paper presents two detailed case reports of female patients with LD. Through an in-depth analysis of their clinical features, it also provides an comprehensive review of the key clinical manifestations of LDS, potential pathogenic mechanisms, and current approaches to genetic diagnosis. The aim is to enhance clinicans′ awareness of LDS and improve corresponding diagnostic and therapeutic strategies.

Aim To explore the role and mechanism of epimedokoreanin B(EKB)in HepaRG cell pyroptosis through endoplasmic reticulum stress and NLRP1-me-diated pyroptosis pathway.Methods The effect of EKB on the viability of HepaRG cells at different con-centrations was determined by MTT assay,and the cell growth status was recorded by Incucyte.Four groups of HepaRG cells were set up.The control group was cul-tured with complete medium for 24 h;the drug admin-istration group was cultured with three concentration gradients of 6.25,12.5 and 25 μmol·L-1 of EKB for 24 h.Western blot was used to detect the expression levels of endoplasmic reticulum stress-related proteins and pyroptosis-related proteins in the cells of each group.Results HepaRG cells showed cytotoxicity at a concentration of 6.25 μmol·L-1 for 24 h,and the half maximal inhibitory concentration(IC50)was 12.41 μmol·L-1.Incucyte recordings of the cell growth status showed that the cells in the control group were in good growth status,and the vesicular pyropto-sis cells appeared in the different concentrations of EKB and the cells swelled and ruptured after 24 h.Western blot showed that the protein expression levels of endoplasmic reticulum stress-related proteins pERK,eIF-2α,ATF-4,GRP78,and CHOP significantly in-creased in HepaRG cells at 25 μmol·L-1 of EKB compared with the control group.The proteins of the classical pathway of cellular pyroptosis mediated by NLRP1,caspase-1,cleaved caspase-1,GSDMD,GS-DMD-N significantly increased in HepaRG cells.Con-clusion EKB administration induces HepaRG cell py-roptosis,and EKB activates HepaRG cells to undergo endoplasmic reticulum stress and activates the NLRP1/caspase-1/GSDMD-mediated pyroptosis pathway.

Objective To investigate the mechanism of action of circ-0058063 regulating ERK/MAPK signaling pathway on ferroptosis in esophageal cancer cells.Methods EC9706 cells were randomly divided into the Control group,the si-NC group,the si-circ-0058063 group,and the si-circ-0058063+ISO group.qRT-PCR was used to detect the expression of circ-0058063 in esophageal cancer tissues and cells;CCK-8 and clone formation assay were used to detect the cell proliferation ability.The levels of Fe2+,malondialdehyde(MDA),glutathione(GSH),and reactive oxygen species(ROS)in cells were detected.Western blot was used to detect the ERK/MAPK signaling pathway and the expression of ferroptosis-related protein in cells.Results The expression level of circ-0058063 in esophageal cancer tissue was significantly higher than that in adjacent tissues(P<0.05);the expression level of circ-0058063 in human esophageal cancer cell EC9706 was significantly higher than that in human normal esophageal epithelial cell HEEC(P<0.05).Compared with the Control group,the expression level of circ-0058063 in cells,cell survival rate,number of cloned cells,GSH level,ratios of p-ERK1/2/ERK1/2 and p-p38MAPK/p38MAPK,as well as the expression levels of SLC7A11 and GPX4 protein in the si-circ-0058063 group were significantly reduced(P<0.05),while the levels of Fe2+,MDA,and ROS in cells were significantly increased(P<0.05).Compared with the si-circ-0058063 group,the expression level of circ-0058063 in cells,cell survival rate,number of cloned cells,GSH level,ratios of p-ERK1/2/ERK1/2 and p-p38MAPK/p38MAPK,as well as the expression levels of SLC7A11 and GPX4 protein in the si-circ-0058063+ISO group were significantly increased(P<0.05),while the levels of Fe2+,MDA,and ROS in cells were significantly decreased(P<0.05).Conclusion Knockdown of circ-0058063 can inhibit the proliferation of esophageal cancer cells and induce ferroptosis,and its mechanism of action may be related to the inhibition of ERK/MAPK signaling pathway activation.

Objective To evaluate the efficacy and safety of a novel intravascular lithotripsy(IVL)balloon—Vesscrack shockwave balloon—for vascular preparation before stent implantation in patients with severe coronary artery calcification(CAC).Methods This was a prospective,single-arm,multicenter study conducted in China from June 2022 to October 2022.Patients with severe CAC were treated with the Vesscrack shockwave balloon for lesion preparation,followed by drug-eluting stent(DES)implantation.Of these,33 patients underwent optical coherence tomography(OCT).The primary endpoint was procedural success,defined as successful stent implantation with residual stenosis≤30％and the absence of in-hospital major adverse events,including cardiac death,target vessel-related myocardial infarction,or target lesion revascularization.Results A total of 170 patients[mean age:(65.9±7.9)years,116 males]were enrolled.After treatment with IVL and DES,the minimum lumen diameter increased significantly compared to baseline[(2.34±0.40)mm vs.(0.95±0.33)mm,P＜0.001],the degree of stenosis was significantly reduced[(13.24±6.60)％vs.(65.18±10.59)％,P＜0.001].Procedural success was achieved in 100％of cases,and device success was 98.8％.The 30-day patient-related cardiovascular clinical composite endpoint(POCE)rate was 0.0,with no target lesion failure,no confirmed or potential thrombotic events were observed.The shockwave energy generator demonstrated excellent stability and ease of use.Among the 33 patients assessed with OCT,after IVL intervention,the maximum calcified area of the lumen[(3.51±1.51)mm2 vs.(2.85±1.80)mm2,P＜0.001],and the minimum lumen area within the target lesion[(3.08±1.04)mm2 vs.(2.02±0.75)mm2,P＜0.001],and after DES intervention,the luminal area of the largest calcified site[(6.59±1.64)mm2 vs.(2.85±1.80)mm2,P＜0.001]and the minimum luminal area within the target lesion[(6.19±1.45)mm2 vs.(2.02±0.75)mm2,P＜0.001]were significantly increased,and the differences were statistically significant.Conclusions The Vesscrack shockwave balloon is effective and safe for vascular preparation in patients with severe CAC prior to stent implantation.It achieves significant calcified plaque modification,high procedural success rates,and minimal complications.

Aim To explore the role and mechanism of epimedokoreanin B(EKB)in HepaRG cell pyroptosis through endoplasmic reticulum stress and NLRP1-me-diated pyroptosis pathway.Methods The effect of EKB on the viability of HepaRG cells at different con-centrations was determined by MTT assay,and the cell growth status was recorded by Incucyte.Four groups of HepaRG cells were set up.The control group was cul-tured with complete medium for 24 h;the drug admin-istration group was cultured with three concentration gradients of 6.25,12.5 and 25 μmol·L-1 of EKB for 24 h.Western blot was used to detect the expression levels of endoplasmic reticulum stress-related proteins and pyroptosis-related proteins in the cells of each group.Results HepaRG cells showed cytotoxicity at a concentration of 6.25 μmol·L-1 for 24 h,and the half maximal inhibitory concentration(IC50)was 12.41 μmol·L-1.Incucyte recordings of the cell growth status showed that the cells in the control group were in good growth status,and the vesicular pyropto-sis cells appeared in the different concentrations of EKB and the cells swelled and ruptured after 24 h.Western blot showed that the protein expression levels of endoplasmic reticulum stress-related proteins pERK,eIF-2α,ATF-4,GRP78,and CHOP significantly in-creased in HepaRG cells at 25 μmol·L-1 of EKB compared with the control group.The proteins of the classical pathway of cellular pyroptosis mediated by NLRP1,caspase-1,cleaved caspase-1,GSDMD,GS-DMD-N significantly increased in HepaRG cells.Con-clusion EKB administration induces HepaRG cell py-roptosis,and EKB activates HepaRG cells to undergo endoplasmic reticulum stress and activates the NLRP1/caspase-1/GSDMD-mediated pyroptosis pathway.

Objective To investigate the mechanism of action of circ-0058063 regulating ERK/MAPK signaling pathway on ferroptosis in esophageal cancer cells.Methods EC9706 cells were randomly divided into the Control group,the si-NC group,the si-circ-0058063 group,and the si-circ-0058063+ISO group.qRT-PCR was used to detect the expression of circ-0058063 in esophageal cancer tissues and cells;CCK-8 and clone formation assay were used to detect the cell proliferation ability.The levels of Fe2+,malondialdehyde(MDA),glutathione(GSH),and reactive oxygen species(ROS)in cells were detected.Western blot was used to detect the ERK/MAPK signaling pathway and the expression of ferroptosis-related protein in cells.Results The expression level of circ-0058063 in esophageal cancer tissue was significantly higher than that in adjacent tissues(P<0.05);the expression level of circ-0058063 in human esophageal cancer cell EC9706 was significantly higher than that in human normal esophageal epithelial cell HEEC(P<0.05).Compared with the Control group,the expression level of circ-0058063 in cells,cell survival rate,number of cloned cells,GSH level,ratios of p-ERK1/2/ERK1/2 and p-p38MAPK/p38MAPK,as well as the expression levels of SLC7A11 and GPX4 protein in the si-circ-0058063 group were significantly reduced(P<0.05),while the levels of Fe2+,MDA,and ROS in cells were significantly increased(P<0.05).Compared with the si-circ-0058063 group,the expression level of circ-0058063 in cells,cell survival rate,number of cloned cells,GSH level,ratios of p-ERK1/2/ERK1/2 and p-p38MAPK/p38MAPK,as well as the expression levels of SLC7A11 and GPX4 protein in the si-circ-0058063+ISO group were significantly increased(P<0.05),while the levels of Fe2+,MDA,and ROS in cells were significantly decreased(P<0.05).Conclusion Knockdown of circ-0058063 can inhibit the proliferation of esophageal cancer cells and induce ferroptosis,and its mechanism of action may be related to the inhibition of ERK/MAPK signaling pathway activation.

Objective:To investigate the effect of anterior and posterior selective fusion strategy on evolution of coronal pattern in patients with Lenke 5C adolescent idiopathic scoliosis (AIS) and whether upper end vertebra (UEV)-1 strategy in anterior surgery would have an effect on postoperative coronal balance.Methods:A total of 108 Lenke 5C AIS patients with at least 2 years follow-up who underwent anterior or posterior selective thoracolumbar fusion surgery from January 2005 to December 2020 were enrolled, with 51 patients in the anterior group and 57 patients in the posterior group. The patients were categorized into three groups (type A, C 7PL-CSVL<20 mm; type B, C 7PL-CSVL ≥20 mm with C 7PL toward the concave side of the main curve; and type C, C 7PL-CSVL≥20 mm with C 7PL toward the convex side of the main curve) to investigate the evolution of coronal balance of each preoperative coronal pattern at the anterior and posterior groups. Parameters such as thoracolumbar Cobb angle, rate of coronal imbalance, and SRS-22 score were recorded at preoperative, 1 week postoperatively, and final follow-up in both groups. Results:The differences of basic date between the two groups were not statistically significant except for the fusion level (5.2±0.7 vs. 5.6±0.9, t=2.497, P=0.014). In the anterior group, a total of 27 patients with preoperative type A, 23 patients with preoperative type A maintained type A at the 1 week postoperatively, and 2 of them were converted to type C at the final follow-up. Four patients with preoperative type A converted to type C at the 1 week postoperatively, and all of them returned to type A at the final follow-up. A total of 23 patients with preoperative type C, four patients with preoperative type C maintained type C at the 1 week postoperatively, and one of them maintained type C at the final follow-up. Nineteen patients with preoperative type C converted to type A at the 1 week postoperatively, and all of them maintained type A at the final follow-up. In the posterior group, a total of 26 patients with preoperative type A, 22 patients with preoperative type A maintained type A at the 1 week postoperatively, and only 2 of these patients converted to type C at the final follow-up. Four of the preoperative type A patients converted to type C at the 1 week postoperatively, and all of them returned to type A at the final follow-up. A total of 29 patients with preoperative type C, thirteen patients with preoperative type C maintained type C at the 1 week postoperatively, and 7 of them maintained type C at the last follow-up. Sixteen patients with preoperative type C converted to type A at the 1 week postoperatively, of whom two converted to type C at the final follow-up. For patients with preoperative type C the rate of coronal imbalance was significantly lower in the anterior group than in the posterior group both in the immediate postoperative period (17% vs. 45%, P<0.05) and at the final follow-up (4% vs. 31%, P=0.038). The rate of coronal imbalance at final follow-up was significantly lower in the UEV-1 group than in the UEV group in the posterior approach (3% vs. 38%, P<0.05), and there was no difference between the two groups in the anterior approach. There were no significant differences in radiographic parameters and SRS-22 scores between the two groups, except for the thoracic Cobb angle at the final follow-up, which was greater in the anterior group than in the posterior group at the final follow-up (19.5±7.3 vs.16.4±5.6, t=2.427, P=0.017). Multivariate logistic regression analysis revealed that anterior surgery and Risser were risk factors for postoperative CIB of preoperative type C ( OR=21.138, P=0.030 and OR=0.406, P=0.048 respectively). Conclusion:For patients with preoperative type A, both anterior and posterior procedures lead to a satisfactory reconstruction of coronal balance. In patients with preoperative type C, anterior surgery acquire a better reconstruction of coronal balance. The strategy of proximal UEV-1 was similar to the strategy of UEV in terms of restoring coronary balance in anterior approach and it was unable to lower the rate of postoperative coronal imbalance. In contrast, UEV-1 strategy in posterior surgery was effective in reducing the rate of postoperative coronal imbalance.

Microglia activation-mediated neuroinflammatory responses serve as a critical pathological ba-sis for the development and progression of various brain diseases.The role of circular RNAs(circRNAs)in the regulation of neuroinflammation is increasingly being recognized.This study aimed to investigate the effect and molecular mechanisms of targeted inhibition of circular RNA Homeodomain Interacting Pro-tein Kinase 3(HIPK3)(circHIPK3)on lipopolysaccharide(LPS)-induced microglial polarization in BV2 cells.The results showed that LPS stimulation significantly induced polarization of BV2 cells towards the pro-inflammatory M1 phenotype and upregulated circHIPK3 expression(P＜0.01).Engineered extra-cellular vesicles(EVs)with rabies viral glycoprotein(RVG)loaded with circHIPK3 siRNA(RVG-EVs-sicHIPK3)were successfully constructed.Transmission electron microscopy(TEM)revealed their typi-cal EV morphology.nanoparticle tracking analysis(NTA)indicated a peak particle size of 70 nmn.And Western blotting analysis confirmed the expression of characteristic membrane marker proteins.Treatment with RVG-EVs-sicHIPK3 significantly suppressed the LPS-induced elevation of inflammatory cytokines(TNF-α,IL-6,IL-1β)in the supernatant and reduced the expression of M1 phenotypic marker proteins(CD16 and CD86)(P＜0.01).Concurrently,RVG-EVs-sicHIPK3 increased the number of mitophago-somes within cells,upregulated the ratio of the autophagy-related proteins LC3-Ⅱ/LC3-I(P＜0.01),and downregulated the expression of the autophagy-related protein p62 and mitochondrial-specific proteins(TOMM20 and TIMM23)(P＜0.01).The mitophagy inhibitor Mdivi-1 significantly reversed the RVG-EVs-sicHIPK3-mediated downregulation of inflammatory cytokine levels,M1 marker proteins,and mito-chondrial protein expression(P＜0.01).This study demonstrates that inhibiting circHIPK3 reduces LPS-induced microglial polarization towards the M1 phenotype.The protective mechanism is closely associated with enhanced mitophagic flux and the promotion of damaged mitochondrial clearance.