Liver fibrosis is caused by various factors such as viral infection， alcohol intake， and metabolism-related damage， leading to the replacement of normal tissue by fibrous scars. As a regulatory factor for cell proliferation， insulin-like growth factor 1 （IGF-1） participates in the regulation of cell cycle， the promotion of cell proliferation and differentiation， and the inhibition of cell apoptosis by binding to its receptor insulin-like growth factor-1 receptor （IGF-1R）. Studies have shown that the IGF-1/IGF-1R signaling pathway can regulate the process of liver fibrosis by affecting the senescence and apoptosis of hepatocytes， the activation and proliferation of hepatic stellate cells， and the dysfunction of endothelial cells. In addition， the IGF-1/IGF-1R signaling system can also regulate multiple mechanisms such as DNA damage repair， cell proliferation， lipid metabolism， cell senescence， and oxidative stress， thereby providing new strategies and potential targets for the prevention and treatment of liver fibrosis. This article summarizes the mechanism of action of IGF-1/IGF-1R and its signal transduction system in mediating liver fibrosis by regulating DNA damage repair in different cells， in order to provide a theoretical basis for the treatment of liver fibrosis.

Copper is an essential trace element in the human body, extensively involved in key physiological and biochemical processes such as antioxidant defense, energy metabolism, neural signaling, and immune regulation. In recent years, increasing research has focused on the potential role of copper dyshomeostasis in the development of chronic diseases. Studies indicate that abnormal copper levels, particularly elevated free copper, may increase the risk of cardiovascular disease, neurodegenerative disorders, diabetes, and cancer by inducing oxidative stress, impairing mitochondrial function, and disrupting immune regulation. Concurrently, copper homeostasis abnormalities have been demonstrated to be closely associated with increased all-cause mortality and accelerated aging. This systematic review comprehensively examined physiological functions, metabolic pathways, and environmental exposure characteristics of copper. It emphasized the epidemiological and mechanistic links between copper metabolism disorders and multiple chronic diseases, while exploring the potential applications of copper ion transporters and chelating agents in disease intervention. This work provides scientific evidence for the prevention, control, and precision treatment of copper-related chronic diseases.

Objective To systematically analyze the characteristics of the disease burden of hypertensive heart disease (HHD) in the elderly (≥60 years) globally and in China from 1990 to 2021, and to predict its future trends from 2022 to 2040, with the aim of providing data support for optimizing comprehensive prevention and control strategies for HHD. Methods Based on the Global Burden of Disease (GBD) 2021 database, the number of prevalent cases and disability-adjusted life years (DALYs) of HHD in the elderly were extracted for the world, China, and five regions categorized by sociodemographic index (SDI). Joinpoint regression was used to analyze the temporal trends of age-standardized prevalence rate and age-standardized DALYs rate of HHD in the elderly. A three-factor decomposition method was applied to evaluate the relative contributions of aging, population growth, and epidemiological changes to the variations in the elderly HHD burden. Additionally, a Bayesian age-period-cohort model was used to predict the elderly HHD burden from 2022 to 2040. Results In 2021, the number of prevalent elderly HHD cases reached 10 283 000 globally and 3 412 400 in China, representing increases of 179.20% and 159.20% respectively, compared with 1990. The DALYs of elderly HHD were 18 812 700 person-years globally and 4 731 400 person-years in China, rising by 76.08% and 29.45% respectively from 1990. Meanwhile, the growth rates of the number of prevalent cases and DALYs of elderly HHD varied across different SDI regions. From 1990 to 2021, the age-standardized prevalence rate of elderly HHD in China, as well as the age-standardized DALYs rate of elderly HHD both globally and in China, showed significant downward trends (all average annual percentage changes<0, all P<0.001). In 2021, the 70-74 years age group accounted for the highest proportion of prevalent cases and DALYs of elderly HHD, both globally and in China. Decomposition analysis revealed that population growth was the dominant factor driving the increase in the elderly HHD burden across all regions. The prediction model results indicated that the number of prevalent cases and DALYs of elderly HHD would continue to rise globally and in China from 2022 to 2040, with the growth rate of the elderly HHD burden in China between 2021 and 2040 expected to exceed the global average. Conclusion Over the past 32 years, although the age-standardized disease rates of elderly HHD have mainly shown a downward trend globally and in China, the absolute number of the disease burden has increased substantially. The projection model indicates a continued upward trajectory, with the growth rate in China higher than the global average. Therefore, there is an urgent need to implement precise prevention and control strategies to effectively mitigate the disease burden of elderly HHD.

Purpose To investigate the role of secreted protein acidic and rich in cysteine(SPARC)expression in the diagnosis and differential diagnosis of mesothelioma.Methods Immunohistochemical EnVision two-step method was used to detect SPARC expression in 40 cases of mesothelioma,4 cases of well-differentiated mesothelial tumour(WDPMT),40 cases of poorly differentiated squamous cell carcinoma of the lung,40 cases of poorly differentiated ad-enocarcinoma of the lung,20 cases each of low-grade and high-grade serous carcinoma of the ovary.The sensitivity and specificity of SPARC,Calretinin,D2-40,and WT-1 expression in mesothelioma were compared and analyzed.Results SPARC showed diffuse strong positive expression in mesothelioma(37/40 cases),medium positive expression in WDPMT(3/4 cases),and focal weak positive expression in a few cases of poorly differentiated squamous cell carcino-ma of the lung(1/40 cases),poorly differentiated adenocarcinoma of the lung(2/40 cases),low-grade serous carci-noma of the ovary(0/20 cases),and high-grade serous carcinoma of the ovary(1/20 cases).In 40 mesotheliomas,the sensitivity of SPARC was 92.5％,and the specificity of SPARC in control tumors(squamous carcinoma of the lung,adenocarcinoma of the lung,and serous carcinoma of the ovary)was 96.7％.Conclusion SPARC is widely expressed in mesotheliomas,with a sensitivity similar to that of Calretinin,D2-40,and WT-1,but with a much higher specificity than other mesothelial markers.It is of great significance in distinguishing between mesothelioma and pulmo-nary poorly differentiated carcinoma and ovarian serous carcinoma.

Objective:To study the anti-inflammatory mechanism of acupoint acupuncture combined with tetramethylpyrazine in regulating the nuclear factor kappa B (NF-κB)/NOD like receptor thermal protein domain associated protein 3 (NLRP3) signaling pathway in a T-2 toxin induced rat model of Kashin-Beck disease.Methods:A total of 40 clean-grade Sprague-Dawley (SD) rats (half male and half female), weighing 180 - 220 g, were divided using a random number table method into model group, tetramethylpyrazine group, acupoint acupuncture combined with tetramethylpyrazine group, and control group, with 10 rats in each group. Rats in the model group, the tetramethylpyrazine group, and the acupoint acupuncture combined with tetramethylpyrazine group were intraperitoneally injected with 1.5 mg/kg of 0.1% T-2 toxin five times per week for 4 consecutive weeks. Rats in both the tetramethylpyrazine group and the acupoint acupuncture combined with tetramethylpyrazine group were intraperitoneally injected with 100 mg·kg -1·d -1 tetramethylpyrazine solution. Meanwhile, rats in the model group and the control group were administered an equivalent volume of physiological saline for consecutive 4 weeks. Acupoint acupuncture combined with tetramethylpyrazine group was used to needle the bilateral "Qu Chi" and "Wei Zhong" of rats with a diameter of 3 - 5 mm, leaving the needle for 20 minutes, once a day, for 4 weeks. After the last injection, the rats were euthanized to collect blood samples and knee joint cartilage. Hematoxylin and eosin staining was performed to observe the pathological changes in the knee joint cartilage of rats. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of osteocalcin (OC), alkaline phosphatase (ALP), β-carboxy-terminal cross-linked telopeptide of type Ⅰ collagen (β-CTX), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Western blot analysis was used to determine protein expression levels of NF-κB p65 and NLRP3. Results:In the control group, intact cartilage surface, middle, and deep structures were observed in the knee joint cartilage of rats. In the model group, pathological changes similar to adult Kashin-Beck disease were observed in the knee joint cartilage. The integrity of the knee joint cartilage of rats in the tetramethylpyrazine group and the acupoint acupuncture combined with tetramethylpyrazine group was significantly improved compared to the model group. Compared with the control group, the levels of OC and ALP in the serum of the model group rats were significantly reduced, while the level of β-CTX was significantly increased ( P < 0.05). Compared with the model group, the levels of OC and ALP in the serum of rats in the tetramethylpyrazine group and the acupoint acupuncture combined with tetramethylpyrazine group were significantly increased, while the levels of β-CTX were significantly decreased ( P < 0.05). The levels of OC and ALP in the serum of rats in the acupoint acupuncture combined with tetramethylpyrazine group were higher than those in the tetramethylpyrazine group, while the level of β-CTX was lower than that in the tetramethylpyrazine group ( P < 0.05). Compared with the control group, the levels of IL-1β, IL-6 and TNF-α in the serum of the model group rats were significantly increased ( P < 0.05). Compared with the model group, the levels of IL-1β, IL-6 and TNF-α in the serum of rats in the tetramethylpyrazine group and the acupoint acupuncture combined with tetramethylpyrazine group were significantly reduced ( P < 0.05). The levels of IL-1β, IL-6 and TNF-α in the serum of rats in the acupoint acupuncture combined with tetramethylpyrazine group were lower than those in the tetramethylpyrazine group ( P < 0.05). Compared with the control group, the expression levels of NF-κB p65 and NLRP3 proteins in the model group rats were significantly increased ( P < 0.05). Compared with the model group, the expression levels of NF-κB p65 and NLRP3 proteins were significantly reduced in the tetramethylpyrazine group and the acupoint acupuncture combined with tetramethylpyrazine group ( P < 0.05). The expression levels of NF-κB p65 and NLRP3 proteins in the acupoint acupuncture combined with tetramethylpyrazine group were significantly lower than those in the tetramethylpyrazine group ( P < 0.05). Conclusion:Acupoint acupuncture combined with tetramethylpyrazine has a good anti-inflammatory effect on T-2 toxin induced Kashin-Beck disease rats, and its mechanism may be related to the downregulation of NF-κB p65 and NLRP3 protein expression.

Objective:To investigate the diagnosis，therapeutic strategy and early prognosis of Scimitar syndrome in pediatric patients.Methods:Clinical data of 21 children with Scimitar syndrome admitted to the Department of Cardiothoracic Surgery of Shanghai Children's Medical Center from January 2014 to December 2021 were retrospectively analyzed，and divided into 11 cases in the infantile-type group and 10 cases in the adult-type group.Results:Twenty-one children with Scimitar syndrome，10 males and 11 females，aged 5 days to 10 years old. Compared with the adult-type group，the infant-type group had a high proportion of preoperative clinical symptoms( P<0.05)，a high concomitant rate of intracardiac malformations (100% vs. 40%， P=0.002)，a big size of aortopulmonary collateral(APC)[(0.77±0.25) mm/kg vs.(0.36±0.13) mm/kg， P=0.016]，a high incidence of pulmonary hypertension(91.0% vs. 50.0%， P=0.038), and a high proportion of severe pulmonary hypertension(50 % vs. 0). There was a high rate of postoperative complications of low cardiac output syndrome (36.4% vs. 0， P=0.034)，prolonged postoperative mechanical ventilation [(73.22±44.75) h vs. (19.5±12.79) h， P=0.007]，and prolonged length of ICU stay[(7.89±3.37) d vs. (2.50±1.26) d， P<0.001]. Eleven cases underwent surgical treatment only，and 10 cases received hybrid operation with APC occlusion. The survival rate of the whole group was 90.5%，and there was no case of pulmonary venous obstruction in the early postoperative period. Systolic pulmonary artery pressure/systolic artery pressure decreased significantly after surgery in 15 children with pulmonary arterial hypertension( P<0.01).Five cases in the infantile-type group still had pulmonary hypertension. Conclusion:Surgical effect of Scimitar syndrome in pediatric patients is satisfactory. Infants with Scimitar syndrome usually have more severe symptoms, higher incidence of severe pulmonary hypertension and relatively longer postoperative recovery time.

Objective:To explore the construction of an evaluation model for aortic root anatomy and calcium burden in patients with bicuspid aortic valve (BAV) stenosis before transcatheter aortic valve replacement (TAVR) based on deep learning (DL) algorithms.Methods:A retrospective collection of 362 BAV stenosis patients who underwent TAVR from September 2023 to May 2024 was performed. All patients underwent cardiac CT angiography. The patients were divided into training group ( n=104), internal validation group ( n=206), and external validation group ( n=52). A DL model was trained on the training dataset to assess aortic root anatomy and calcification burden. The evaluation included the segmentation accuracy of the algorithm, the measurement performance of key anatomical structures (i.e., valve leaflets and type-1 and type-2 fusion raphe), and calcification burden, as well as the measurement efficiency. Overall segmentation performance was assessed using the average Dice coefficient (ADC). The fine-scale segmentation quality was validated by the 95th-percentile Hausdorff distance (HD-95) and the average symmetric surface distance (ASSD). The consistency of the measurement results was assessed using the Pearson correlation coefficient and the intraclass correlation coefficient ( ICC) with a two-way mixed model for absolute agreement. In addition, the total time and total mouse movement distance required for manual assessment versus the DL model on the validation datasets were recorded and compared. Results:The algorithm demonstrated excellent segmentation performance on aortic root anatomical targets, achieving outstanding consistency within both internal and external validation datasets (0.955

Objective:To retrospectively analyze the efficacy and feasibility of surgical management in patients with cervical dysphagia secondary to Diffuse idiopathic skeletal hyperostosis(DISH)of the cervical spine.Methods:A retrospective analysis was conducted on 6 patients who presented with dysphagia as the primary symptom, were diagnosed with cervical DISH, and underwent surgical treatment in the Department of Otorhinolaryngology Head and Neck Surgery of The Second Xiangya Hospital of Central South University from January 2018 to February 2024. There were 5 males and 1 female, aged from 65 to 78 years (70.2±4.7 years). The duration of dysphagia prior to admission was 13 to 18 months (14.7±2.2 months). All patients had the symptom of dysphagia, and at least one other clinical manifestation of cervical DISH (dyspnea, restricted neck mobility, sleep apnea, odynophagia). One patient had undergone tracheotomy due to laryngeal obstruction before surgery. Surgical intervention was performed after failure of conservative management in all patients. All patients underwent anterior cervical osteophyte resection via the Smith-Robinson approach without concomitant spinal fusion. In the patient with prior tracheotomy for airway obstruction, epiglottoplasty and right arytenoidectomy were performed simultaneously. The swallowing function was evaluated by water swallow test, FEES, M. D. Anderson Dysphagia Inventory. Clinical and imaging evaluations were conducted for follow-uppostoperatively. Preoperative and 30-day post operative data were statistically analyzed using paired samples t-test.Results:Cervical computed tomography revealed osteophyte involvement from C2 to T1 with a median of 4 vertebral segments affected. The most frequently involved vertebral segments were C4-C6 (all 6 patients were involved). The anteroposterior diameter of the most prominent osteophyte was 12.0 to 20.0 mm (16±3.1 mm). The time to resumption of a regular diet was 6 to 20 days(12.7±5.3 days), and the time to remove the nasogastric tube was 8 to 25 days(15.2±6.2 days). In the patient with prior tracheotomy, the tracheostomy tube was successfully decannulated 30 days after initial tube capping following conversion to a metal tube. All cervical DISH-related symptoms except for limited neck mobility improved postoperatively. Both water swallow test and the Rosenbek Penetration-Aspiration Scale showed significant improvement postoperatively. At 30 days postoperatively, MDADI scores significantly improved in all domains: l global (73.33±10.33), emotional (85.56±8.35), functional (83.33±5.89), and physical (82.08±6.60). No major perioperative complications occurred. and the length of hospital stay was 7 to 10 days (7.8±1.2 days). The follow-up time was 12 to 84 months (43.7±27.2 months). All patients maintained sustained symptom relief, with no evidence of osteophyte recurrence during follow-up.Conclusion:Cervical DISH is an under-recognized causes of dysphagia in elderly patients and warrants attention from otolaryngologists. For patients erefractory to conservative treatment, anterior resection of cervical osteophytes via the Smith-Robinson approach is a safe, minimally invasive procedure with favorable short-and long-term outcomes in improving swallowing function.

Objective:To construct and evaluate a radiomics model for predicting perineural invasion in patients with intrahepatic cholangiocarcinoma (ICC).Methods:Clinical data of 144 patients with ICC undergoing surgery in the People’s Hospital of Zhengzhou University ( n=113) and the Affiliated Cancer Hospital of Zhengzhou University ( n=31) from January 2018 to June 2023 were retrospectively analyzed, including 80 males and 64 females, aged (58.8±10.1) years. The patients were randomly divided into a training set ( n=100) and a test set ( n=44) at a ratio of 7: 3. The former set was used to build the model for predicting perineural invasion, and the latter was used to evaluate the model. Enhanced CT images and clinical data of the patients were collected, and features related to perineural invasion were screened. A light gradient boosting machine was used to construct an imaging genomics model. The model was evaluated using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results:Univariate and multivariate logistic regression analysis showed that none of the clinical features were associated with neural invasion in ICC patients (all P>0.05). Six, 25, 32, and 37 radiomics features were obtained by screening the intratumoral, 2 mm peritumoral, 5 mm peritumoral, and 8 mm peritumoral regions, respectively. The area under the ROC curve for predicting perineural invasion in ICC patients was 0.849 (95% CI: 0.774-0.923) in the training set and 0.745 (95% CI: 0.597-0.894) in the test set for the intratumoral model, 0.966 (95% CI: 0.938-0.995) and 0.750 (95% CI: 0.604-0.896) for the 5mm peritumoral model, 0.936 (95% CI: 0.892-0.980) and 0.792 (95% CI: 0.644-0.939) for the 2mm peritumoral model, and 0.961 (95% CI: 0.929-0.992) and 0.689 (95% CI: 0.526-0.853) for the 8mm peritumoral model. The area under the ROC curve, accuracy, sensitivity, and specificity of the combined intratumoral and 5mm peritumoral model for predicting perineural invasion were 0.927 (95% CI: 0.878-0.976), 88.0%, 84.5%, and 89.8% in the training set, and 0.849 (95% CI: 0.737-0.960), 77.3%, 85.2%, and 72.0% in the test set, respectively. The calibration curve showed a deviation between the calibration curve of the combined intratumoral and 5mm peritumoral model and the ideal line, but it could achieve basic consistency. DCA showed that when the threshold was between 0.18 and 0.70, the combined intratumoral and 5mm peritumoral model could bring clinical net benefit to patients when predicting neural invasion. Conclusion:The intratumoral and 5mm peritumoral imaging genomics model based on enhanced CT features can effectively predict neural invasion and offer clinical benefits in patients with ICC.

Sustained inflammatory responses are closely related to various severe diseases,and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment.Natural products have garnered considerable concern for the treatment of inflammation.Huanglian-Wumei decoction(HLWMD)is a classic prescription used for treating inflammatory diseases,but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated.Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory,we successfully obtained berberine(BBR)-chlorogenic acid(CGA)supramolecular(BCS),which is an herbal pair from HLWMD.Using a series of characterization methods,we confirmed the self-assembly mechanism of BCS.BBR and CGA were self-assembled and stacked into amphiphilic spherical supra-molecules in a 2:1 molar ratio,driven by electrostatic interactions,hydrophobic interactions,and π-πstacking;the hydrophilic fragments of CGA were outside,and the hydrophobic fragments of BBR were inside.This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules.Compared with free molecules,BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide(LPS)-induced pyroptosis.Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB(NF-κB)p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.