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.

Objective To explore the impact of gender factors in participant selection during bioequivalence studies,and to provide insights for improving the screening success rate in subsequent trials.Methods A retrospective study was con-ducted to summarize the screening information of healthy subjects in the bioequivalence study conducted in the Phase Ⅰ Clinical Trial Laboratory of the Affiliated Hospital of Xiangnan University from July 2021 to July 2023.The number of failed screening ca-ses in different stages of screening for each project was counted,and the influence of gender factors on subject screening was ana-lyzed.Results A total of 32 bioequivalence studies involving 2 794 subjects,including 1 816 males and 978 females,were in-cluded in the study.The proportion of males was higher in vital signs and BMI abnormalities,and the proportion of females was higher in ECG abnormalities and active withdrawal,and the pass rate was lower in males than in females(40.0％ vs.45.8％),and the existence of the two was statistically significant(P＜0.05).The results of PC A showed that the distribution of data in males was more dispersed,and the distribution of data in females was centralized,and the two could be clearly differentiated.Binary lo-gistic regression analysis showed significant differences between males and females in laboratory test screening failures and BMI(P＜0.05).Further analysis showed that the screening failure rates of blood biochemistry,urine routine,coagulation function and blood transfusion were higher in males than in females,but the screening failure rates of blood routine were lower than those of fe-males.Conclusions Gender is an important influencing factor in the screening process of bioequivalence studies.Including subjects with appropriate gender ratios can help improve enrollment speed and reduce clinical trial costs.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Objective: To explore the differential lipid metabolites in the plasma of mice with idiopathic pulmonary fibrosis(IPF). Methods : Thirty SPF C57BL/6 male mice were randomly divided into 2 groups with 15 mice in each group. The experimental groups were divided into control group and bleomycin(BLM) group. The model of idiopathic pulmonary fibrosis was induced by one-time intratracheal infusion of BLM(1 mg/kg). Hematoxylin-eosin(HE) staining was used to observe the lung histopathology. The collagen fiber deposition in lung tissue was observed by Sirius red staining. The differential lipid metabolites in plasma of IPF mice were screened and enriched by lipidomics. Results : HE staining showed that the pulmonary tissue structure was disordered, alveolar septum was broken and alveolar wall was destroyed in BLM group. Sirius red staining showed a large amount of collagen fiber deposition in the lung interstitium of BLM group. The results of lipidomics analysis showed that the lipid metabolism profile of BLM group changed, 15 differential lipid metabolites were screened out, of which 11 differential lipid metabolites were up-regulated, and 4 differential lipid metabolites were down-regulated, mainly concentrated in glycerophosphoglycerophosphates, glycerophosphocholines, steroid lactones, etc. Conclusion The lipid metabolism profile of BLM group mice changes, differential lipid metabolites such as phosphoglycolate phosphatase(PGP)(18:0/18:0), PGP(i-12:0/i-24:0), PGP(i-13:0/a-25:0), and phosphatidylcholine(PC)(18:0/14:0), PC(18:3/16:0), lysophosphatidylcholine(LPC)(16:1), and LPC(18:3) may play an important role in the progression of IPF. These findings provide a new reference for further study of the molecular mechanism of IPF, and also provide a potential new target for clinical treatment.

Objective:To analyze the correlation between mental health status and metabolic syndrome (MetS) in health checkup people.Methods:It was a cross-sectional study, 2 920 participants who received health checkup in the Health Examination Center of Peking University Third Hospital from January 2019 to December 2023 were selected using cluster sampling method. Their general information, physical examination, biochemical indicators, body composition, and self-evaluation scores on the Symptom Checklist-90 (SCL-90) were collected. According to the inclusion and exclusion criteria, a total of 2 813 study subjects were included, and divided into the MetS group and the non-MetS group based on whether they had MetS. The differences in general demographic information, body composition, blood biochemistry, and SCL-90 scores between the two groups were compared. Binary Logistic regression analysis was used to explore the correlation between mental health status and MetS.Results:Of the 2 813 subjects included, 1 576 were males (56.0%) and 1 237 were females (44.0%), with an average age of (41.7±11.0) years, the MetS group had 586 cases (20.8%) and the non-MetS group had 2 227 cases (79.2%). The MetS group had higher levels of age, body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, total cholesterol, triglycerides, low density lipoprotein cholesterol (LDL-C), fasting blood glucose, glycosylated hemoglobin (HbA 1c), free thyroxine(FT4), total triiodothyronine (TT3), free triiodothyronine (FT3), waist-to-hip ratio, visceral fat area, body fat percentage, uric acid/creatinine, homocysteine (Hcy), aspartate aminotransferases (AST), and alanine transaminase (ALT) levels, as well as higher scores for somatization, hostility, paranoia, and other factor compared to the non-MetS group (all P<0.05), while high density lipoprotein cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR) levels were lower than those in the non-MetS group (all P<0.05). The proportion of male, and the positive rates of SCL-90, somatization, interpersonal sensitivity, hostility, paranoia and other factor in the MetS group were higher than those in the non-MetS group (all P<0.05). Multifactorial analysis showed that individuals with a positive SCL-90 assessment had a 1.34 times higher risk of MetS than those with a negative assessment ( OR=1.34, 95% CI: 1.06-1.68; P=0.014). Among them, individuals with positive somatization ( OR=2.02, 95% CI: 1.25-3.28; P=0.004) and hostility ( OR=1.61, 95% CI: 1.02-2.56; P=0.042) had increased risk of MetS. Conclusion:Poor mental health status increases the risk of MetS.

Objective To screen and analyze the differentially expressed genes (DEGs) related to oxidative stress in a silicosis mouse model using transcriptome sequencing technology. Methods i) A total of 30 workers without occupational dust-exposed history were selected as the control group and 17 patients with silicosis were selected as the silicosis group using a judgment sampling method. The levels of glutathione and malondialdehyde in the plasma of workers in the two groups were determined by enzyme-linked immunosorbent assay. ii) RAW264.7 cells in the logarithmic growth phase were randomly divided into the control group and the silica group, treated with 0 and 50 mg/L silica suspensions for 24 hours. Protein expression of superoxide dismutase 2 (SOD2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the cells was determined by Western blotting. iii) The specific pathogen free male C57BL/6 mice were randomly divided into the control group and the silicosis model group, with 10 mice in each group. Mice were exposed to 50 μL of 0.9% sodium chloride solution and silica suspension at a mass concentration of 100 g/L, respectively, using a single tracheal exposure method. After 28 days of exposure, the pathological changes of mouse lung tissues were observed. Transcriptome sequencing was used to screen DEGs in the lung tissues of the silicosis mouse model, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. The expression of DEGs was verified using quantitative real-time polymerase chain reaction (qPCR). Results i) The level of malondialdehyde in the patients′ plasma was higher (P<0.01), while the level of glutathione was lower (P<0.01) in the silicosis group than that of the control group. ii) The relative expression of SOD2 protein decreased (P<0.05), while the relative expression of IL-6 and TNF-α proteins increased (all P<0.05) in the silica group of RAW264.7 cells compared with the control group. iii) The pathological results of lung tissues showed that the alveolar structure of mice was destroyed and silicotic nodules were formed in the silicosis model group. Transcriptome sequencing identified 3 703 DEGs, of which 3 199 were significantly down-regulated and 504 were significantly up-regulated. The GO enrichment analysis results showed that the DEGs were significantly enriched in biological processes such as oxidative stress, inflammation, immunity and hypoxia, with cellular components mainly located in membranes, cytoplasm, and nucleus. Molecular functions were enriched in oxidoreductase activity, protein binding, and adenosine triphosphate binding. The KEGG enrichment analysis results showed that the DEGs were mainly involved in the phosphatidylinositol 3-kinase-protein kinase B signaling pathway, cyclic adenosine monophosphate signaling pathway, chemokine signaling pathway, and apoptosis signaling pathway. A total of 28 DEGs involved in the "oxidative stress response" pathway were screened by GO enrichment analysis. The qPCR verification results showed that the relative expression of DEGs carbonic anhydrase 3 (Car3), matrix metalloproteinase 9 (Mmp9), and MutY DNA glycosylase (Mutyh) involved in the "oxidative stress response" of lung tissues in the silicosis model group were lower than those of the control group (all P<0.05). Conclusion Oxidative stress response exists in silicosis patients. The oxidative stress-related genes Car3, Mmp9, and Mutyh are altered in the mouse lung tissues of the silicosis model through the oxidative stress pathway, suggesting that they could be new targets for the treatment of silicosis.

Objective To investigate the effects of Yiqi Wenyang Lishui Formula(derived from Wuling San combined with Astragali Radix and Descurainiae Semen Lepidii Semen)on cardiac function and remodeling in heart failure(HF)patients with yang deficiency and fluid retention syndrome and to analyze risk factors for influencing therapeutic efficacy.Methods A total of 120 HF patients with yang deficiency and fluid retention syndrome admitted to Liaocheng Hospital of Traditional Chinese Medicine from February 2022 to January 2024 were enrolled and randomly divided into observation group(n=60)and control group(n=60)using a random number table.The control group received conventional western therapy,while the observation group received Yiqi Wenyang Lishui Formula additionally.Both groups were treated for 2 months.Changes in cardiac function indicators and remodeling markers were observed.Clinical efficacy was evaluated,and univariate and binary logistic regression analyses were performed to identify independent risk factors affecting treatment outcomes.Results(1)The total effective rate was 81.67％(49/60)in the observation group versus 70.00％(42/60)in the control group.Intergroup comparison(by chi-square test)showed that the efficacy in the observation group was superior to the control group(P＜0.05).(2)After treatment,both groups showed significant reductions compared to those before treatment in left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),and N-terminal pro-brain natriuretic peptide(NT-proBNP)(P＜0.01).The reduction in LVEDD,LVESD,and serum NT-proBNP levels in the observation group was significantly greater than that in the control group(P＜0.05 or P＜0.01).(3)Univariate analysis revealed that New York Heart Association(NYHA)functional classification,LVEDD,LVESD,and NT-proBNP levels were significantly associated with the therapeutic efficacy of the Yiqi Wenyang Lishui Formula in heart failure patients with yang deficiency and fluid retention syndrome(P＜0.05).(4)Logistic regression identified NYHA classification,LVEDD,LVESD,and NT-proBNP as independent risk factors(P＜0.05)in affecting therapeutic effect of Yiqi Wenyang Lishui Formula in treating HF with yang deficency and fluid retention syndrome,increasing the risk of ineffective treatment by 4.12-fold,1.21-fold,1.19-fold,and 1.00-fold,respectively.Conclusion Yiqi Wenyang Lishui Formula effectively improves cardiac function and remodeling in HF patients with yang deficiency and fluid retention syndrome.NYHA classification,LVEDD,LVESD,and NT-proBNP are independent risk factors for influencing efficacy,warranting close monitoring for optimized therapeutic adjustments.

Objective To explore the impact of gender factors in participant selection during bioequivalence studies,and to provide insights for improving the screening success rate in subsequent trials.Methods A retrospective study was con-ducted to summarize the screening information of healthy subjects in the bioequivalence study conducted in the Phase Ⅰ Clinical Trial Laboratory of the Affiliated Hospital of Xiangnan University from July 2021 to July 2023.The number of failed screening ca-ses in different stages of screening for each project was counted,and the influence of gender factors on subject screening was ana-lyzed.Results A total of 32 bioequivalence studies involving 2 794 subjects,including 1 816 males and 978 females,were in-cluded in the study.The proportion of males was higher in vital signs and BMI abnormalities,and the proportion of females was higher in ECG abnormalities and active withdrawal,and the pass rate was lower in males than in females(40.0％ vs.45.8％),and the existence of the two was statistically significant(P＜0.05).The results of PC A showed that the distribution of data in males was more dispersed,and the distribution of data in females was centralized,and the two could be clearly differentiated.Binary lo-gistic regression analysis showed significant differences between males and females in laboratory test screening failures and BMI(P＜0.05).Further analysis showed that the screening failure rates of blood biochemistry,urine routine,coagulation function and blood transfusion were higher in males than in females,but the screening failure rates of blood routine were lower than those of fe-males.Conclusions Gender is an important influencing factor in the screening process of bioequivalence studies.Including subjects with appropriate gender ratios can help improve enrollment speed and reduce clinical trial costs.

Objective:To assess the impact of induction chemotherapy sensitivity on the prognosis and larynx preservation rates in patients with locally advanced hypopharyngeal cancer and to identify risk factors influencing induction chemotherapy sensitivity.Methods:This study included patients with locally advanced (stage III-IV) hypopharyngeal cancer who received induction chemotherapy as initial treatment at the Eye & ENT Hospital of Fudan University between August 2017 and September 2022. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, enrolled patients were classified into the sensitive group and the resistant group according to their response to induction chemotherapy. Chi-square tests and Log-rank tests were used to compare the objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and laryngeal preservation rate (LPR) between groups. Propensity score matching (PSM) was employed to accurately evaluate the impact of induction chemotherapy sensitivity on prognosis in real-world settings. Univariate and multivariate logistic regression analyses were performed to identify risk factors for induction chemotherapy resistance in locally advanced hypopharyngeal cancer.Results:A total of 197 patients with locally advanced hypopharyngeal cancer who received induction chemotherapy as initial treatment were included in, comprising 195 males and 2 females, with ages ranging from 36 to 74 years. Among them, 155 patients (78.68%) were classified into the sensitive group and 42 patients (21.32%) into the resistant group. The overall response rate (ORR) of induction chemotherapy in this cohort was 78.68%, with a five-year OS rate of 63.7%. The sensitive group had significantly better OS (mOS 6.32 vs. 5.05 year), PFS (mPFS 5.71 vs. 3.09 year) and a significantly higher LPR (91.6% vs. 69.0%) ( P<0.05). After propensity score matching, all covariates were balanced between the two groups, and the sensitive group showed significant improvement in OS ( P<0.05), while, no significant difference was observed in PFS and LPR between the two groups. Logistic regression analysis revealed that risk factors for induction chemotherapy failure in locally advanced hypopharyngeal cancer included: smoking status ( OR [95% CI]=4.751 [1.887-11.961]), tumor location in the posterior pharyngeal wall ( OR [95% CI]=2.988 [1.264-7.063]), and cN2-3 stage ( OR [95% CI]=3.641 [1.109-11.954]) ( P<0.05). Conclusions:Induction chemotherapy sensitivity significantly affects the prognosis of locally advanced hypopharyngeal cancer, which is influenced by various risk factors, including smoking status, tumor sublocation, and clinical N stage.