Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder primarily caused by pathogenic variants in the TSC1 or TSC2 genes. It is characterized by multisystem hamartomatous lesions and neuropsychiatric manifestations. Here we report a young male patient with TSC involving multiple organs, caused by a heterozygous frameshift mutation in TSC2 (c.2071delC, p.Arg691Alafs^*7). The patient initially presented with classic facial angiofibromas and hypomelanotic macules, and subsequently developed psychiatric and behavioral disturbances with auditory hallucinations. Neuroimaging revealed an intracranial mass lesion, which was confirmed as a subependymal giant cell astrocytoma on postoperative histopathology following surgery performed at an outside institution. After admission, the patient underwent a comprehensive diagnostic workup, and multidisciplinary treatment evaluation revealed extensive multisystem involve-ment, including the nervous system, skin, kidneys, lungs, heart, eyes, pancreas, liver and bones. Combined with relevant literature, this article discusses the molecular mechanisms, clinical phenotypes, and comprehensive management of TSC, in order to provide a reference for the standardized and individualized management of this disease.

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

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.

Objective To study the effect of auditory and speech development after cochlear implant(CI)in children with bilateral cochlear nerve deficiency(CND)and its influencing factors.Methods A total of 20 children with bilateral CND were included in the study,of which 5 were implanted bilaterally and 15 unilaterally.CT of the temporal bone showed stenosis of the cochlear aperture in 14 cases and atresia of the cochlear aperture in 6 cases.There were 8 cases accompanied by other inner ear malformations,and 12 cases with no accompanying inner ear mal-formations.MRI of the internal auditory canal showed 1 nerve in 5 cases,2 nerves in 6 cases,3 nerves in 8 cases,and 4 nerves in 1 case.There were 6 cases in which the EABR was not elicited and 14 cases in which it was elicited.The postoperative auditory and speech abilities of the subjects were evaluated using categories of auditory perform-ance(CAP)and speech intelligibility rating(SIR).Results ① The CAP(P＜0.001)and SIR(P＜0.001)scores of the children with stenosis of the cochlea nerve canal were higher than those of the patients with atresia of the cochlea nerve canal.② The more nerve roots in the internal auditory canal,the higher the score of CAP(P=0.003)and SIR(P=0.008).③ CAP score of the children with EABR elicited was higher than that of the children without EABR elicited(P=0.030).The difference in SIR scores was not statistically significant(P=0.14).④The differences in CAP and SIR between those with bilateral CI and unilateral CI,as well as between those with and without other inner ear malformations,were not statistically significant(P＞0.05).Conclusion Children with bi-lateral CND had significant postoperative improvement in auditory function but poor speech development after CI.Postoperative auditory speech ability was related to the condition of the cochlear foramen,the number of nerve roots in the internal auditory canal,and whether or not the EABR was elicited intraoperatively.

Objective:To explore the application effect of integrated traditional Chinese and Western medicine nursing based on"whole course case management mode"in patients with coronary heart disease(CHD)after percutaneous coronary inter-vention(PCI).Methods:This randomized controlled study enrolled 98 CHD patients who underwent PCI for the first time at Jiangsu Province Hospital of Chinese Medicine between February 2022 and May 2023.The patients were divided into in-tervention group(n=49)and control group(n=49).The patients in intervention group received whole course case man-agement model-based integrated traditional Chinese and Western medicine nursing plan,while those in the control group received routine nursing care after PCI.Scores of Morisky Medication Adherence Scale(MMAS-8),Cardiovascular Health Score(CHS),China questionnaire of quality of life in patients with cardiovascular diseases(CQQC)and incidence of adverse cardiac events were compared between two groups after 6 and 12 months.Results:Compared with patients in control group after intervention,those in intervention group had significant higher scores of MMAS-8[6 months:(6.63±0.83)points vs.(5.96±0.95)points,12 months:(6.85±0.96)points vs.(5.84±0.91)points],CHS[(8.10±1.37)points vs.(7.45±1.28)points],CQQC[(92.73±7.44)points vs.(88.16±2.88)points],and significant lower incidence of adverse cardiac events(14.29％vs.36.73％)(P＜0.05 or＜0.01).Conclusion:The integrated traditional Chinese and Western medicine nursing intervention plan based on the whole course case management model could effectively improve medication compliance,strengthen cardiovascular health behavior,reduce the incidence of adverse cardiac events,and improve quality of life in CHD patients after PCI.

Objective To evaluate the prognosis and safety of patients with advanced pancreatic ductal adenocarcinoma(PDAC)who received I-125 seed implantation in treatment with anti-PD-1 monoclonal antibody+chemotherapy.Methods A retrospective analysis was conducted on patients with stage Ⅳ metastatic PDAC who received anti-PD-1 combined chemotherapy treatment at Yixing Hospital,Jiangsu University from Jan 2021 to Jun 2023.Patients were divided into two groups based on whether they received I-125 seed implantation:the I-125 seed implantation+anti-PD-1 monoclonal antibody+Chemotherapy group(IPC group)and the anti-PD-1 monoclonal antibody+chemotherapy group(PC group).The follow-up period ranged from 2 to 24 months,with a median follow-up time of 9 months.The prognosis of patients was analysed in combination with peripheral blood biomarkers.The peripheral lymphocyte subsets of patients in different treatment groups were preliminarily analysed by flow cytometry.Results A total of 13 patients were included,with 5 in the IPC group and 8 in the PC group.Progression-free survival(PFS)and overall survival(OS)in the IPC group were significantly longer than those in the PC group.The treatment in the IPC group was relatively safe,adverse reactions were controllable.The neutrophil-lymphocyte ratio(NLR)and CD4/CD8 ratio indicated that the prognosis of the IPC patients was better.The levels of regulatory T cells(Treg)and active regulatory T cells(aTreg)cells in the IPC patients were reduced after treatment compared with those of the PC patients.Conclusion The addition of I-125 seed implantation can improve the prognosis of patients with advanced PDAC who receive anti-PD-1 monoclonal antibody+chemotherapy,the post-treatment levels of patients'circulating aTreg cells are reduced,and the combination therapy has good safety.

OBJECTIVE To explore the intervention mechanism of Shangke Lengtongtie on cold hyperalgesia in KOA mice based on the HMGB1/CXCL12/CXCR4 signaling axis.METHODS Monosodium iodoacetate(MIA)was used for the intra-articular injec-tion into the knee joint to establish mice model of knee osteoarthritis(KOA).Peripheral blood monocytes were extracted from mice,cultured,and then reinfused into the tail vein of the mice.Subsequently,in vivo animal imaging was used to observe the recruitment sites of these monocytes.The cold hyperalgesia threshold was measured at various time points in each group of mice.Hematoxylin and eosin(HE)staining was used to evaluate the level of synovial pathological changes.ELISA was employed to detect the expression of in-flammatory factors IL-1β,TNF-α,and pain mediators CGRP and Substance P in mouse serum.Western blot and qPCR methods were used to detect the protein and gene expression of cold hyperalgesia-related indicators such as TRPA1,TRPM8,HMGB1,CXCL12,CXCR4,Collagen Ⅰ,and Netrin-1 in synovial tissue,as well as DCC in dorsal root ganglia(DRG)tissue.RESULTS In vivo ima-ging showed that after the monocytes were reinfused into KOA mice,they were recruited to the knee joint area,with the HMGB1 group exhibiting a greater recruitment of circulating monocytes at the knee joint.Additionally,compared to the control group,the KOA group and HMGB1 group showed inflammatory pathological changes in the synovium,increased expression of serum inflammatory factors and pain mediators,reduced cold hyperalgesia threshold,and upregulated protein and gene expression of cold hyperalgesia-related indica-tors in synovial and DRG tissues.The changes were more significant in the HMGB1 group compared to the KOA group(P<0.05).Af-ter treatment with Shangke Lengtongtie or GL intervention,synovial inflammation was alleviated,serum inflammatory factors and pain mediators decreased,cold hyperalgesia threshold increased,and the upregulation of cold hyperalgesia-related indicator protein and gene expression levels was significantly reversed(P<0.05).CONCLUSION Shangke Lengtongtie exerts a beneficial effect on the mitigation of synovitis and cold hyperalgesia in KOA mice,a therapeutic mechanism that possibly mediated through the inhibition of the HMGB1/CXCL12/CXCR4 signaling axis.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To explore the mediating effect of family care on disease perception and medical coping strategies in maintenance hemodialysis(MHD)patients,and to provide theoretical basis for clinical intervention.Methods:This study was a prospective study,136 patients who received MHD treatment at Shanxi Integrated Traditional Chinese and Western Medicine Hospital from January 2023 to January 2025 as the research subjects were selected.The family adaptation,partnership,growth,affection,resolve index(APGAR)questionnaire was used to evaluate family care,the brief illness perception questionnaire(BIPQ)was used to assess disease perception,and medical coping modes questionnaire(MCMQ)was used to evaluate medical coping strategies.The correlation between family care,disease perception,and medical coping strategies was analyzed by Pearson correlation analysis,and the mediating effect of family care on disease perception and medical coping strategies was tested by Bootstrap method(5000 repeated samples).Result:Family care was negatively correlated with disease perception(r=-0.428,P＜0.05),positively correlated with positive coping(r=0.513,P＜0.05),and negatively correlated with negative coping(r=-0.397,P＜0.05).The mediation effect analysis shows that family care partially mediates the relationship between disease perception and positive coping(mediation effect value-0.173,accounting for 35.67％of the total effect),and also partially mediates the relationship between disease perception and negative coping(mediation effect value 0.184,accounting for 41.26％of the total effect).Conclusion:Family care is an important mediating variable in the impact of disease perception on medical coping strategies,clinical practice can improve patients' disease perception and promote the adoption of positive coping strategies by enhancing family care.

Objective To explore the application effect of 3D printed individualized model in the treatment of complex ankle fractures(AF).Methods Patients with complex AF admitted to our hospital from July 2021 to October 2022 were selected and divided into the control group and the observation group using a random number table method,with 50 cases in each group.Patients in the control group were received minimally invasive reduction and internal fixation,while these in the observation group were given minimally invasive reduction and internal fixation under the guidance of 3D printed individualized model.The surgical conditions,ankle joint reduction,stress indicators[norepinephrine(NE)and angiotensin Ⅱ(AngⅡ)],ankle function and postoperative complications were compared between the two groups.Results There were 2 patients in the observation group and 3 patients in the control group were lost to follow-up 12 months after surgery.Compared with the control group,the observation group showed a decrease in the intraoperative blood loss,shortened surgical time,hospitalization time,and weight-bearing activity time,and an increase in the anatomical reduction rate(P<0.05).The observation group had lower serum levels of NE and AngⅡ 1 and 3 days after surgery(P<0.05)and higher Kofoed score and American Orthopedic Foot and Ankle Society(AOFAS)scores 1,6,and 12 months after surgery(P<0.05),as well as lower incidence of postoperative complications(P<0.05)than those in the control group.Conclusion For the treatment of complex AF,3D printed individualized model assisted the formulation of minimally invasive reduction and fixation surgical plans before surgery can shorten surgical time,reduce stress injury,decrease the risk of complications,and simultaneously increase the anatomical reduction rate and improve ankle joint function,thereby accelerating postoperative recovery of patients.