BACKGROUND:Cervical disc herniation can cause pain in the neck and shoulder area,as well as radiating pain in the upper limbs.The incidence rate is increasing year by year and tends to affect younger individuals.Fully understanding the biomechanical characteristics of the cervical spine in adolescents is of great significance for preventing and delaying the onset of cervical disc herniation in this age group. OBJECTIVE:To reconstruct cervical spine models for both healthy adolescents and adolescent patients with cervical disc herniation utilizing finite element analysis techniques,to analyze the motion range of the C1-T1 cervical vertebrae as well as the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and the cartilage of the small joints. METHODS:A normal adolescent's cervical spine and an adolescent patient with cervical disc herniation were selected in this study.The continuous scan cervical spine CT raw image data were imported into Mimics 21.0 in DICOM format.The C1-T1 vertebrae were reconstructed separately.Subsequently,the established models were imported into the 3-Matic software for disc reconstruction.The perfected models were then imported into Hypermesh software for meshing of the vertebrae,nucleus pulposus,annulus fibrosus,and ligaments,creating valid geometric models.After assigning material properties,the final models were imported into ABAQUS software to observe the joint motion range of the C1-C7 cervical vertebrae segments under different conditions,and to analyze the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and small joint cartilage of each cervical spine segment. RESULTS AND CONCLUSION:(1)In six different conditions,the joint motion range of the C1 vertebra in the cervical spine models of both normal adolescent and adolescent patient with cervical disc herniation was higher than that of the other vertebrae.Additionally,the joint motion range of each cervical spine segment in normal adolescent was greater than that in adolescent patient with cervical disc herniation.(2)In the cervical spine model of normal adolescent,the maximum stress values in the annulus fibrosus and nucleus pulposus were found on the left side during C2-3 flexion conditions(0.43 MPa and 0.17 MPa,respectively).In the cervical spine model of adolescent patient with cervical disc herniation,the maximum stress values were found on the left side during C7-T1 flexion conditions(0.54 MPa and 0.18 MPa,respectively).(3)In the cervical spine model of normal adolescent,the maximum stress value on the endplate was found on the left side of the upper endplate of C3 during flexion conditions(1.46 MPa).In the model of adolescent patient with cervical disc herniation,the maximum stress value on the endplate was found on the left side of the lower endplate of C7 during flexion conditions(1.32 MPa).(4)In the cervical spine model of normal adolescent,the maximum stress value in the small joint cartilage was found in the C2-3 left rotation conditions(0.98 MPa).In adolescent patient with cervical disc herniation,the stress in the small joint cartilage significantly increased under different conditions,especially in C1-2,with the maximum stress found during left flexion(3.50 MPa).(5)It is concluded that compared to normal adolescent,adolescent patient with cervical disc herniation exhibits altered cervical curvature and a decrease in overall joint motion range in the cervical spine.In adolescent with cervical disc herniation,there is a significant increase in stress on the annulus fibrosus,nucleus pulposus,and endplates in the C7-T1 segment.The stress on the left articular cartilage of the C1-2 is notable.Abnormal cervical curvature may be the primary factor causing these stress changes.

Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8⁺ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8⁺ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.

Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a "brake-release and accelerator-pressing" approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu²⁺) and iron ions (Fe³⁺) were liberated from Cu-PB. The direct chelation of Cu²⁺ and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the "brake-release" strategy). The release of Cu²⁺ and Fe³⁺ ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the "accelerator-pressing" strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Objective To explore the influencing factors of microcirculation dysfunction in patients with anterior wall acute myocardial infarction(AMI)and to establish a relevant prediction model.Methods A total of 130 patients with anterior wall AMI,whose microcirculation function was assessed by caIMR after receiving percutaneous coronary intervention(PCI)at Shanghai Sixth People's Hospital of China from January 2017 to September 2020,were enrolled in this study.The patients were divided into abnormal microcirculation resistance group(n=52)and normal microcirculation resistance group(n=78).The clinical data were compared between the two groups.The regression analysis was used to analyze the influencing factors of microcirculation dysfunction.Results In the abnormal microcirculation resistance group the contrast agent consumption,the onset-to-operation time,the Gensini total score and the LAD Gensini score were(121.92±31.37)mL,(10.51±5.12)min,(97.91±31.77)points and(69.36±13.15)points respectively,which were significantly higher than(109.03±28.2)mL,(4.94±2.94)min,(81.05±35.22)points and(54.45±23.48)points respectively in the normal microcirculation resistance group,the differences in the above indexes between the two groups were statistically significant(all P＜0.05).A prediction model covering interventional strategies was established,and its accuracy was higher than that of a conventional model,its AUC compared with the conventional model was 0.91 to 0.87,indicating that this model could well predict the risk of microcirculation dysfunction in patients with AMI after receiving PCI.Conclusion This prediction model can promptly identify high-risk microcirculation dysfunction patients with anterior wall AMI after receiving PCI.

Purpose/Significance To design a comprehensive data platform to meet the needs of collecting and sharing survey data on meteorological sensitive diseases,so as to enhance monitoring capabilities for meteorological sensitive diseases in China.Method/Process Through various methods such as data extraction,data exchange,data import and customized collection,disease data,meteoro-logical data,environmental data and diagnosis and treatment data are processed and integrated into the platform for unified management.Result/Conclusion This platform realizes the functions of data collection,aggregation,visualization display and data sharing,which can provide support for scientific researchers in various bases across the country to better manage and utilize meteorological sensitive disease survey data.

Objective To explore the clinical application value of simple resection in the treatment of pancreatic solid pseudopapillary tumor(SPT).Methods Retrospective analysis of clinical and follow-up data of pancreatic SPT patients who underwent simple pancreatectomy and conventional pancreatectomy from January 2015 to December 2022 in the pancreatic cystic tumor database of Huashan Hospital,Fudan University.A total of 87 patients with pancreatic SPT,including 14 cases underwent simple resection and 73 cases underwent conventional resection,were included.The average age was(36.2±11.7)years old,and females accounting for 87.4％.Results The accuracy of preoperative imaging diagnosis reached 88.5％.Simple resection had a significant advantage over conventional resection in terms of surgical time[(138.3± 56.4)min vs.(241.2±89.2)min,P＜0.05].Simple resection was not inferior to conventional resection in terms of common postoperative complications.Out of 87 cases,only 3 patients in conventional resection group experienced postoperative recurrence and metastasis,and all recurrent patients were still alive.There was no statistically significant difference in postoperative pancreatic endocrine and exocrine dysfunction,and quality of life between simple resection group and conventional resection group.Conclusions Simple resection of pancreatic SPT is reasonable and feasible,but the risks in actual clinical work cannot be ignored.Therefore,selective simple resection of SPT has certain clinical application value.

Middle-aged and elderly patients with femoral neck fracture often suffer from basic diseases. Conservative treatment will significantly increase the incidence of complications. At present, surgical treatment is mostly advocated. Internal fixation is one of the effective treatment methods for middle-aged and elderly patients with femoral neck fracture. It has the advantages of improving hip joint function, accelerating patient recovery, and improving patient quality of life. At present, there are many choices of internal fixation in the world, each has its own advantages and disadvantages, and there is no unified standard. Different surgical methods can be selected according to various factors such as fracture type, patient′s physical condition and surgical auxiliary technology. This article reviews the clinical progress of internal fixation for femoral neck fractures in middle-aged and elderly patients from four aspects: the characteristics of femoral neck fractures in middle-aged and elderly patients, common internal fixation methods, 3D printing guide plate auxiliary technology and artificial intelligence auxiliary technology.

Objective To analyze the influencing factors of survival of patients with airway stenosis requiring clinical interventions after lung transplantation. Methods Clinical data of 66 patients with airway stenosis requiring clinical interventions after lung transplantation were retrospectively analyzed. Univariate and multivariate Cox’s regression models were adopted to analyze the influencing factors of survival of all patients with airway stenosis and those with early airway stenosis. Kaplan-Meier method was used to calculate the overall survival and delineate the survival curve. Results For 66 patients with airway stenosis, the median airway stenosis-free time was 72 (52,102) d, 27% (18/66) for central airway stenosis and 73% (48/66) for distal airway stenosis. Postoperative mechanical ventilation time [hazard ratio (HR) 1.037, 95% confidence interval (CI) 1.005-1.070, P=0.024] and type of surgery (HR 0.400, 95%CI 0.177-0.903, P=0.027) were correlated with the survival of patients with airway stenosis after lung transplantation. The longer the postoperative mechanical ventilation time, the higher the risk of mortality of the recipients. The overall survival of airway stenosis recipients undergoing bilateral lung transplantation was better than that of their counterparts after single lung transplantation. Subgroup analysis showed that grade 3 primary graft dysfunction (PGD) (HR 4.577, 95%CI 1.439-14.555, P=0.010) and immunosuppressive drugs (HR 0.079, 95%CI 0.022-0.287, P<0.001) were associated with the survival of patients with early airway stenosis after lung transplantation. The overall survival of patients with early airway stenosis after lung transplantation without grade 3 PGD was better compared with that of those with grade 3 PGD. The overall survival of patients with early airway stenosis after lung transplantation treated with tacrolimus was superior to that of their counterparts treated with cyclosporine. Conclusions Long postoperative mechanical ventilation time, single lung transplantation, grade 3 PGD and use of cyclosporine may affect the survival of patients with airway stenosis after lung transplantation.

Zhigancao Tang （also known as Fumaitang） is a classic formula for treating "intermittent pulse and palpitations" and is widely used in clinical practice. Sanjia Fumaitang， included in the Catalogue of Ancient Classical Formulas （First Batch） published by the National Administration of Traditional Chinese Medicine of China in 2018， is derived from this formula. This paper employed bibliometric methods to comprehensively investigate and summarize the historical evolution， drug composition， herb origins and preparation， prescription meanings， and ancient and modern applications of Zhigancao Tang， analyzed the composition and usage of Zhigancao Tang， and discussed the reasons and applications of the "Fumaitang" variants created by Wu Jutong. A total of 47 valid pieces of data from 38 ancient texts were included. Results showe that Zhigancao Tang originates from the Treatise on Cold Damage （Shang Han Lun）， and the name "Fumaitang" is also recorded in the formula's description. Converted to modern measurements from the Han dynasty system， the recommended preparation for Zhigancao Tang includes 55.2 g of fried Glycyrrhizae Radix et Rhizoma， 41.4 g of Cinnamomi Ramulus， 27.6 g of Ginseng Radix et Rhizoma， 220 g of fresh Rehmannia glutinosa， 27.6 g of Asini Corii Colla， 53 g of Ophiopogonis Radix， 45 g of Cannabis Fructus， and 90 g of Jujubae Fructus. All herbs should be decocted with 1 400 mL of yellow rice wine and 1 600 mL of water until 600 mL. Once the Asini Corii Colla is fully dissolved， the decoction should be taken warm at a dosage of 200 mL， three times a day. Zhigancao Tang is effective for replenishing Qi， warming Yang， nourishing Yin， and nourishing blood and is primarily used to treat “intermittent pulse and palpitations” caused by deficiencies in heart Yin and Yang， as well as malnutrition of the heart meridian and conditions like lung atrophy. Modern applications mainly focus on cardiovascular and cerebrovascular diseases， including arrhythmias， coronary heart disease， and premature ventricular contractions. The findings from this research provide a reference for the further development of Zhigancao Tang.