AIM:To investigate the molecular mechanism underlying ferroptosis induced by celastrol(Cel)in huamn pancreatic cancer cell line PANC-1.METHODS:The viability of PANC-1 cells was analyzed by MTT assay,and the effects of Cel on cell proliferation were analyzed using EdU and colony formation assays.Flow cytometry and fluores-cence microscopy were used to assess and observe changes in lipid reactive oxygen species(ROS)levels,respectively,while the levels of malondialdehyde(MDA),glutathione(GSH)and Fe2+were measured using specific kits.The protein expression of glutathione peroxidase 4(GPX4)was evaluated by Western blot,and GPX4 ubiquitination was measured by immunoprecipitation.RESULTS:It was found that the viability,proliferation and colony formation in PANC-1 cells de-creased gradually as the concentration of Cel increased.Addition of Cel alone to the cells reduced both cell rounding and viability,while treatment with ferrostatin-1(Fer-1)alone or in combination with Cel had no effect on either cell morpholo-gy or viability.Fluorescence staining of lipid ROS with BODIPYTM 581/591 C11 followed by flow cytometry analysis showed significantly increased levels of green fluorescence indicative of oxidized lipid ROS,which were further increased after treatment of the cells with Cel.Treatment of the cells with both Cel and Fer-1 reduced the green fluorescence and lip-id ROS levels.Treatment with Cel also increased the levels of MDA and Fe2+,relative to the controls,which reducing the levels of GSH,while addition of both Cel and Fer-1 to the cells restored the levels of MDA,Fe2+,and GSH to those of the control group.CONCLUSION:Treatment with Cel reduces the proliferation of pancreatic cancer cells by inducing fer-roptosis through promoting the ubiquitination and degradation of GPX4.

Objective:To analyze the hotspots and trends of the researches on artificial intelligence (AI) in the diagnosis and treatment of traumatic brain injury (TBI).Methods:Based on the core database of Web of Science, the studies over AI in the diagnosis and treatment of TBI published from January 2000 to June 2024 were obtained by searching with the subject headings. VOSviewer software was used to analyze the publication year trend, country publication volume, country cooperation network, author publication volume, author citation frequency and author cooperation network. CiteSpace software was also used to identify key words with a significant rise in frequency over a short period of time to obtain the research trends.Results:A total of 2 662 relevant studies were retrieved, from which 677 related with AI in the diagnosis and treatment of TBI were finally enrolled. The number of published studies per year generally showed a rapid growth from 2018 to 2023. The United States had the highest number of publications as a country (362 studies). The author Camarillo had the most publications (9 studies). Rehabilitation was the keyword with the highest frequency (133 times) and the clustering topics containing the three largest number of keywords were virtual reality (VR), mild TBI, and deep learning. The keywords of mobile application, mobile health and intracranial pressure showed a significant increase in frequency from January 2022 to June 2024.Conclusions:VR technology, mild TBI and deep learning technology are the research hotspots of AI in TBI diagnosis and treatment. Mobile apps, mobile health, and intracranial pressure may be new research trends for AI in the diagnosis and treatment of TBI.

BACKGROUND:With the in-depth research of hydrogel materials,the applicable fields of hydrogel have been gradually broadened,and carrying stem cells for disease treatment has become a new direction of research,but how to construct a hydrogel suitable for stem cell growth is the key problem that needs to be solved at present. OBJECTIVE:To investigate the physicochemical properties of chitosan-chitosan biguanide hydrochloride-collagen composite hydrogels and to evaluate their ability to load mouse umbilical cord mesenchymal stem cells. METHODS:The hydrogels were prepared by physically cross-linking chitosan,chitosan biguanide hydrochloride and collagen with the cross-linking agents β-glycerophosphate sodium and sodium bicarbonate,and the suitable hydrogels were screened according to the gel formation time and gel formation effect(noted as Gel-1,Gel-2 and Gel-3 in this way).Morphology,porosity,swelling properties,and degradability of the three groups of hydrogels were observed by scanning electron microscopy.Hemolysis experiments were performed to examine the hemolysis of the three groups of hydrogels.The mouse umbilical cord mesenchymal stem cells were co-cultured with the hydrogel with the best comprehensive performance of characterization.The cytotoxicity,cell survival and adhesion effect of the composite hydrogel were determined to evaluate the performance of this hydrogel loaded with umbilical cord mesenchymal stem cells. RESULTS AND CONCLUSION:(1)Scanning electron microscopy characterization results showed that all three groups had porous mesh structures inside,and the internal structure of Gel-2 and Gel-3 with the addition of chitosan biguanide hydrochloride was more porous and three-dimensional.(2)The hydrogel porosity of the Gel-3 group was higher than the remaining two groups,with high porosity and uniform pore size distribution.(3)The swelling performance of all three groups of hydrogels was above 100%,and the swelling performance of hydrogels with chitosan biguanide hydrochloride component was better.(4)The degradation rate of the three groups of hydrogels could be degraded by more than 90%in a time scale of 15 days,with good degradation performance.(5)The results of the hemolytic properties showed that the absorbance values measured by each group of hydrogels carrying chicken erythrocytes were basically the same as those of saline carrying chicken erythrocytes,and no hemolysis occurred.(6)The toxicity experiment and living and dead cell staining showed that the survival rate of umbilical cord mesenchymal stem cells in each group of hydrogels was above 100%,indicating that there was no obvious cytotoxicity.Umbilical cord mesenchymal stem cells could survive under the hydrogel package and the hydrogels had a positive effect on the survival rate of umbilical cord mesenchymal stem cells.(7)The cells in the umbilical cord mesenchymal stem cell adhesion assay can survive under the hydrogel package and can adhere to the surface of the hydrogel with normal morphology.

Hyperuricemic nephropathy （HN）， a secondary renal damage common in clinical practice， is characterized by early concealing and continuous progression. The understanding of HN in traditional Chinese medicine （TCM） is from a macroscopic perspective. According to the TCM theory， HN is caused by the combination of external pathogens and internal injuries， with the main pathogenesis being root deficiency combined with superficial excess and deficiency-excess in complexity. In western medicine， the understanding of HN is from the microscopic perspective， which holds that the occurrence of HN is the result of inflammation， oxidative stress， renin-angiotensin-aldosterone system （RAAS） activation， and metabolic abnormalities. The TCM syndromes of HN include internal dampness and heat， obstruction in dampness and turbidity， deficiency of spleen and kidney， and deficiency of kidney yin. Accordingly， the prescriptions should clear heat and dampness， remove dampness and turbidity， tonify spleen and kidney， and nourish kidney yin， respectively. In addition to TCM prescriptions， single herbal medicines and their extracts， Chinese patent medicines， and external applications of Chinese medicines have played a significant role in the treatment of HN， promoting the application of TCM in the treatment of HN. Moreover， the integrated traditional Chinese and western medicine has also played a role in the treatment of HN， enriching the treatment schemes of HN. Different from common kidney diseases such as acute and chronic glomerulonephritis and nephrotic syndrome， HN with particularity should be carefully differentiated in clinical practice. This article systematically summarizes the research progress in the treatment of traditional Chinese medicine and integrated traditional Chinese and western medicine on hyperuricemic nephropathy with TCM and integrated traditional Chinese and western medicine， aiming to enrich the system and theory of HN treatment and further guide the clinical practice.

Diabetic kidney diseases （DKD） is one of the main microvascular complications of diabetes. According to the available studies， the initial factor of DKD is glomerular injury. However， in recent years， more and more studies have confirmed that renal tubular injury plays a key role in the development of DKD. Taking renal tubules and their interstitium as therapeutic targets has become a new idea for the treatment of DKD. Traditional Chinese medicine （TCM） can treat renal tubular injury in DKD via multiple pathways， targets， and links， demonstrating significant therapeutic effect and slight side effects. According to the etiology and pathogenesis of DKD， doctors differentiate different syndromes such as deficiency of both Qi and Yin， deficiency of spleen and kidney Yang， and Qi deficiency and blood stasis and then adopt the therapies of nourishing kidney and strengthening essence， clearing heat and eliminating dampness， tonifying Qi and nourishing yin and so on， which have shown significant effect in the treatment of renal tubular injury in DKD. This paper summarizes the experimental studies about the treatment of renal tubular injury in DKD by TCM compound prescriptions， as well as the effective parts， extracts， and active ingredient of Chinese herbal medicines. Chinese herbal medicines and their derivates can regulate Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB）， nuclear factor erythroid 2-related factor 2 （Nrf2）/antioxidant response element （ARE）， transforming growth factor-β₁ （TGF-β₁）/Smads and other signaling pathways to treat renal tubular injury from resisting oxidative stress， inhibiting apoptosis of renal tubular epithelial cells， and blocking renal tubular epithelial-mesenchymal transformation. With this review， we hope to provide a theoretical basis for the development and clinical application of new drugs for renal tubular injury in DKD.

Cyclin-dependent kinase 9 (CDK9) activity is correlated with worse outcomes of triple-negative breast cancer (TNBC) patients. The heterodimer between CDK9 with cyclin T1 is essential for maintaining the active state of the kinase and targeting this protein-protein interaction (PPI) may offer promising avenues for selective CDK9 inhibition. Herein, we designed and generated a library of metal complexes bearing the 7-chloro-2-phenylquinoline CˆN ligand and tested their activity against the CDK9-cyclin T1 PPI. Complex 1 bound to CDK9 via an enthalpically-driven binding mode, leading to disruption of the CDK9-cyclin T1 interaction in vitro and in cellulo. Importantly, complex 1 showed promising anti-metastatic activity against TNBC allografts in mice and was comparably active compared to cisplatin. To our knowledge, 1 is the first CDK9-cyclin T1 PPI inhibitor with anti-metastatic activity against TNBC. Complex 1 could serve as a new platform for the future design of more efficacious kinase inhibitors against cancer, including TNBC.

Objective:To establish a model C-GALAD for detecting hepatocellular carcinoma (HCC) from the chronic liver disease and healthy people based on the serum markers.Methods:A clinical cohort including 229 hepatocellular carcinoma patients, 2 317 patients with chronic liver disease and 982 healthy people, was retrospectively collected from eight hospitals or physical examination institutions from April 2018 to October 2020. The data were divided into a training set and a testing set by stratified sampling with a 6∶4 ratio. A predictive model was established on the training set using a logistic backward regression method and validated on the testing set. In addition, clinical data from March to July 2021 in Beijing You′ an Hospital affiliated to Capital Medical University, including 84 patients with liver cancer and 204 patients with chronic liver disease collected were used for external independent validation of the model. The receiver operating characteristic curve (ROC) area under curve (AUC), the sensitivity and the specificity were used to evaluate the effectiveness of the model.Results:Through the logistic backward regression method, the seven signatures including age, gender, alpha-fetoprotein (AFP), alpha-fetoprotein alloplasm-3 ratio (AFP-L3%), des-gamma-carboxyprothrombin(DCP), platelet (PLT) and total bilirubin (TBIL) were selected as risk factors in the detection model. The area under the ROC curve (AUC) of the model on the testing set was 0.954, with an 88.04% sensitivity and a 94.85% specificity, and the AUC of model on the external independent validation set was 0.943, with an 89.29% sensitivity and a 90.2% specificity, which were better than other published models.Conclusion:The C-GALAD Ⅱ model can accurately predict the risk of hepatocellular carcinoma occurrence, and thus provide a trustworthy diagnosis method of hepatocellular carcinoma.

Objective:To evaluate the clinical efficacy and safety of SpyGlass-guided laser lithotripsy for large common bile duct (CBD) stones with diameter>2 cm.Methods:From August 2015 to August 2018, a total of 157 patients with large CBD stones at the First Affiliated Hospital of Shandong First Medical University who met the inclusion criteria were randomly divided into SpyGlass group ( n=78, underwent SpyGlass-guided laser lithotripsy) and laparoscopic common bile duct exploration (LCBDE) group ( n=79, underwent LCBDE) by using random numbers. Non-inferiority test was used for rates of one-time stone removal and total stone removal, and the non-inferiority margin was set to 10%. The transform rate, incidence of short-term complications, hospital stay, and quality of life (assessed by the gastrointestinal quality of life index) were compared between the two groups. Results:The total success rates of stone clearance were 92.3% (72/78) and 96.2% (76/79) in the SpyGlass group and LCBDE group, respectively ( P=0.023), with valid non-inferiority hypothesis. The one-time stone removal rates were 83.3% (65/78) and 96.2% (76/79), respectively ( P=0.124), with invalid non-inferiority hypothesis. There were no significant differences in the incidence of transform [7.7% (6/78) VS 3.8% (3/79), P=0.294] or short-term complications [5.1% (4/78) VS 10.1% (8/79), P=0.246] between the two groups. Compared with the LCBDE group, the SpyGlass group had a shorter hospital stay (5.65±0.94 d VS 8.84±1.54 d, P=0.001) and higher scores of gastrointestinal quality of life index (1 month after operation: 99.85±4.36 VS 91.51±5.47, P=0.001; 3 months after operation: 131.24±3.32 VS 112.32±7.77, P=0.001). Conclusion:For large CBD stones, the efficacy of SpyGlass-guided laser lithotripsy is not inferior to LCBDE, and it is less invasive. In the future, SpyGlass-guided laser lithotripsy could be an important option for the treatment of large CBD stones.

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TSCI have dyskinesia and sensory disturbance that can cause various life-threaten complications. The patients with traumatic spinal cord injury (TSCI), seriously affecting the quality of life of patients. Based on the epidemiology of TSCI and domestic and foreign literatures as well as expert investigations, this expert consensus reviews the definition, injury classification, rehabilitation assessment, rehabilitation strategies and rehabilitation measures of TSCI so as to provide early standardized rehabilitation treatment methods for TSCI.