Liver fibrosis is the common pathological process in the progression of various chronic liver diseases to liver cirrhosis， and it greatly affects the prognosis of patients with chronic liver diseases. As a novel adipokine， Chemerin participates in the metabolism of glucose and lipids and inflammation， and various studies have shown that the expression level of Chemerin is correlated with the degree of liver fibrosis， suggesting that Chemerin may be involved in the process of liver fibrosis by regulating metabolism and inflammation. Chemerin has shown certain potential in the auxiliary diagnosis of liver fibrosis and the intervention against the progression of liver fibrosis. This article reviews the potential role and mechanism of action of Chemerin in the process of liver fibrosis， in order to provide new ideas for the diagnosis and treatment of liver fibrosis.

[Objective] To explore the clinical features of IgG4-related urinary diseases so as to provide reference for the diagnosis and treatment of such diseases. [Methods] The clinical data of 4 cases of IgG4-related urinary system diseases diagnosed and treated in Xijing Hospital of Air Force Medical University during Aug.2019 and Dec.2023 were retrospectively collected.Here, we report on the diagnosis and treatment of these patients, analysing their symptoms, serology, imaging and pathology as well as their treatment and outcomes. [Results] The patients included 2 male and 2 female.The lesions were involved with the retroperitoneum and urinary system.Three patients had symptoms of lumbar pain.The imaging manifestations were complex, including retroperitoneal mass involving urinary system organs in 2 cases, tabdense shadow of the right kidney in 1 case, and simple cystic mass of kidney in 1 case.Serum IgG4 value was not detected before surgery.All patients underwent radical surgical treatment.Postoperative pathology showed fibrous tissue hyperplasia with a large number of plasma cells, lymphocytes, a few neutrophil infiltrates, and lymphoid follicles and obliterated vasculitis in some specimens.The number of IgG4⁺ plasma cells was more than 10 in all tissues under high power microscope.After surgery, 3 patients had symptoms improved, and serum IgG4 value was within the normal range; 1 patient (patem 3) had elevated IgG4 value during follow-up, received subsequent hormone therapy, and the serum IgG 4 level remained stable. [Conclusion] The symptoms of IgG4-related diseases involving the urinary system are non-specific, and the imaging findings are various, easily confused with other diseases.Early detection of serum IgG4 and biopsy pathology can help clinicians make correct diagnosis in the early stage.

Objective To investigate the impact of two different surgical methods, orthotopic kidney transplantation and abdominal heterotopic kidney transplantation, on the surgical outcomes of pig-to-pig kidney transplantation and the short-term survival of recipient pigs after surgery. Methods Twenty-four Bama miniature pigs were divided into two groups, with 12 pigs in each group, and underwent orthotopic kidney transplantation and abdominal heterotopic kidney transplantation, respectively. The perioperative indicators of the recipient pigs, renal blood perfusion, the overall incidence rate of complications and survival rate were compared between the two surgical methods. Results The total surgical time, renal artery anastomosis time, renal vein anastomosis time, cold ischemia time and total ischemia time were all shorter in the abdominal heterotopic kidney transplantation group than in the orthotopic kidney transplantation group, with statistically significant differences (all P<0.05). The number of satisfactory renal perfusion cases was higher in the abdominal heterotopic kidney transplantation group than in the orthotopic kidney transplantation group (83% vs. 75%), but the difference was not statistically significant (P>0.05). The total incidence of postoperative complications was 33% in the heterotopic kidney transplantation group, with a survival rate of 92%, and the cause of death was rupture of the vascular anastomosis. The total incidence of postoperative complications was 50% in the orthotopic kidney transplantation group, with a survival rate of 83%, and the causes of death were renal vein thrombosis and renal artery thrombosis. There were no statistically significant differences in the total incidence of postoperative complications and survival rates between the two groups (all P>0.05). Conclusions Compared with orthotopic kidney transplantation, abdominal heterotopic kidney transplantation showes better surgical outcomes in pig-to-pig kidney transplantation and is more beneficial for the short-term survival of recipient pigs after surgery. This provides experience for improving the stability of pig-to-non-human primate kidney xenotransplantation models in the future.

Objective To analyze the expression levels of a-smooth muscle actin (α-SMA) and Vimentin in spindle cells and their relationship with the prognosis of patients with myxofibrosarcoma (MFS). Methods The imaging, clinical, and pathological data of 61 patients with MFS were collected. All patients were confirmed by surgical and postoperative pathological examination. Immunohistochemical methods were used to determine the positive proportion of α-SMA and Vimentin. The correlation between the expression levels of α-SMA and Vimentin in spindle cells and prognosis was analyzed. Results The positive rates of α-SMA and Vimentin expression in MFS tissues were 68.85% and 60.66%, respectively. The expression of Vimentin was not significantly correlated with 3-year OS and DFS (P=0.351, P=0.284). The expression of α-SMA was significantly correlated with OS and DFS (P=0.030, P=0.017), and patients with high expression of α-SMA have shorter OS and DFS. Conclusion Determining α-SMA level can help evaluate the prognosis of patients with MFS and guide clinical treatment.

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

Ferroptosis, a regulated cell death process distinct from apoptosis, is characterized by iron dysregulation and reactive oxygen species (ROS) accumulation. After intracerebral hemorrhage (ICH), decreased cerebral blood flow and iron released from erythrocytes trigger lipid peroxidation-particularly of polyunsaturated fatty acids (PUFAs)-through a cascade of reactions in local brain tissues, promoting ferroptosis. Mitochondrial dysfunction and neuroinflammation further elevate ROS, exacerbating lipid peroxidation and accelerating neuronal ferroptosis. Thus, PUFA peroxidation and associated metabolic pathways play a critical role in ICH-related neuronal damage. This review summarizes current understanding of how PUFA peroxidation contributes to ferro-ptosis after ICH, discusses key regulatory mechanisms involving lipid and iron metabolism, and highlights potential therapeutic strategies targeting ferroptosis to improve neurological outcomes.
Ferroptosis/physiology* ; Humans ; Cerebral Hemorrhage/pathology* ; Lipid Peroxidation ; Fatty Acids, Unsaturated/metabolism* ; Reactive Oxygen Species/metabolism* ; Iron/metabolism* ; Animals ; Mitochondria/metabolism*

OBJECTIVE To explore the mechanism by which casticin （CAS） promotes wound healing in superficial second- degree burned rats through phosphatidylinositol 3-kinase （PI3K）/protein kinase B （AKT）/mammalian target of rapamycin （mTOR） signaling pathway. METHODS Rats were randomly assigned to a control group （physiological saline）， a model group （5% sodium carboxymethyl cellulose blank matrix）， low- and high-dose CAS groups （15 mL of CAS solution at concentrations of 30 and 60 mmol/L， respectively）， a high dose CAS plus LY294002 group [a mixture of 15 mL CAS solution （60 mmol/L） and PI3K inhibitor LY294002 solution （20 μmmol/L）]， and a positive control group （thick application of Jingwanhong ointment 0.5-1.0 cm）， with 15 rats in each group. Except for the control group， the other groups were subjected to a superficial second-degree burn rat model by igniting a mixture of burn fuel on the skin surface， and the administration was applied topically within two hours after the burn. After 28 days of administration， the wound healing rate of the burned rats was calculated， the histopathological changes in the central tissue of the rat’s burned wound were observed， and the levels of tumor necrosis factor α （TNF-α）， interleukin-1β （IL- 1β）， IL-6， matrix metalloproteinase-2 （MMP-2）， MMP-9 and vascular endothelial growth factor （VEGF） in the serum of rat were detected. The phosphorylation levels of related proteins in the PI3K/AKT/mTOR signaling pathway in the burned tissue of the rats were also detected. RESULTS Compared with the control group， the rats in the model group showed epidermal and superficial dermal damage in skin tissue， poor healing status， inflammatory cell infiltration， and incomplete tissue structure. The levels of IL-6， IL-1β， TNF-α， MMP-2 and MMP-9 in the serum were significantly increased （P＜0.05）， and the levels of VEGF in the serum and the phosphorylation levels of E-mail：caodongsheng@ahmu.edu.cn PI3K， AKT， mTOR proteins in the central tissue of the burned wound were significantly decreased （P＜0.05）. Compared with the model group， the pathological changes and the levels of the above indicators in the serum and central tissue of the burned wound in the CAS low- and high-dose groups were significantly reversed （P＜0.05）， and the changes in the CAS high-dose group were significantly more pronounced than those in the CAS low- dose group （P＜0.05）. The addition of the PI3K inhibitor LY294002 could reverse the promoting effect of CAS on the wound healing of superficial second-degree burned rats （P＜0.05）. CONCLUSIONS CAS can promote the healing of superficial second- degree burned wounds in rats， and its mechanism of action may be related to the activation of the PI3K/AKT/mTOR signaling pathway.

OBJECTIVE To evaluate the accuracy of three individualized drug delivery tools， i.e. JPKD， SmartDose and NextDose， in predicting tacrolimus dose and blood concentration after kidney transplantation， and analyze the influential factors of prediction accuracy. METHODS The clinical data of adult hospitalized patients treated with tacrolimus after kidney transplantation from January 2021 to June 2023 were retrospectively collected. Three individualized dosing tools， i.e. JPKD， SmartDose and NextDose， were used to predict the dose and plasma concentration of tacrolimus. The absolute prediction error （APE） and prediction error （PE） between the measured value and the predicted value， and prediction success rate were calculated （APE＜30% indicating a good forecast）. Pearson assay or Spearman assay was used to analyze the correlation between the predicted dosage and actual dosage， as well as the predicted and measured blood concentration values using three software； univariate analysis was used to investigate the influential factors for prediction accuracy of JPKD， SmartDose and NextDose. RESULTS A total of 110 hospitalized patients were included in this study， and tacrolimus doses and plasma concentrations were monitored. The predicted doses of JPKD， SmartDose and NextDose were （2.0±0.7）， （2.7±1.9）， （1.8±0.8） mg， their measured value was （1.9±0.6） mg， and the correlation coefficients between the predicted values and the measured value were 0.841， 0.450， 0.247 （P＜0.001）； the median APEs were 6.00%， 52.07% and 30.40%， and the median PEs were 5.00%， 18.50% and －3.50%； the prediction success rates were 98.45%， 30.05% and 49.22%. The predicted values of tacrolimus concentrations using JPKD， SmartDose， NextDose were （6.74±3.36）， （6.93±5.02）， 9.00（5.80±12.60） ng/mL， the measured value was 8.64（7.11，9.77） ng/mL， and the correlation coefficients between the predicted values and the measured value were 0.997 （P＜0.001）， －0.066 （P＝0.360）， 0.920 （P＜0.001）. The median APEs were 5.54%， 45.91% and 35.56%， and PEs were －4.94% （median）， －17.050% （median） and 36.93% （average value）； the prediction success rates were 97.93%， 32.64% and 37.31%. Univariate analysis showed that the dosage， blood concentration， body weight， transplantation time and others were related to the prediction accuracy （P＜0.05）. CONCLUSIONS The good prediction rates of tacrolimus dose and blood concentration in kidney transplant patients using three personalized drug delivery tools， from high to low， are JPKD， NextDose， and SmartDose， suggesting that JPKD can be prioritized in clinical use.

Objective:To identify the association between CD4 +T lymphocyte (CD4) counts and physical frailty among HIV-infected people aged 65 years and older, and evaluate whether this association will be modified by the indicators of body composition. Methods:From May to October 2022, 485 elderly HIV-infected patients receiving antiretroviral therapy (ART) were recruited from 7 antiviral treatment sites in Jiangjin District Center for Disease Control and Prevention, Chongqing. The data of basic characteristics (age and gender), living habits (smoking and drinking) and disease history (metabolic diseases, cardiovascular and cerebrovascular diseases, respiratory disease and malignant tumors) were collected through the face-to-face investigation with self-made questionnaires. Fried Frailty Scale was used to evaluate the status of physical frailty. Physical fitness (walking speed, grip strength, height, and weight) and body composition (skeletal muscle mass, body fat mass, and basal metabolic rate) were measured. The antiretroviral treatment data were obtained from the China AIDS Integrated Prevention and Treatment Data information management system. The prevalence of physical frailty was calculated among the HIV-infected patients. The potential effects of CD4 counts on physical frailty were explored by using multivariate logistic regression. Subgroup analyses were repeated in the logistic regression with muscle mass, body fat mass, and other indicators of body composition as subgroup variables to determine whether the association might be modified by body composition.Results:The age of 485 patients were (72±5) years old, of which 48.2% (234 cases) were>70 years old and 70.9% (344 cases) were male, and all of whom had initiated the ART treatment. The prevalence of physical frailty among these patients was 7.4% (36/485). Multivariate logistic regression showed that after adjusting for age, sex, smoking, drinking, body composition index, ART duration, viral load and the number of comorbidities, increased CD4 cell level was associated with decreased prevalent risk of physical frailty among elderly HIV-infected patients. For every increase of 5.0×10 7 CD4 cells/L, the prevalent risk of physical frailty decreased by 12% [ OR (95% CI): 0.88 (0.76-1.01)]. Compared with the low CD4 cell level group, the risk of physical frailty in those with normal CD4 cell level decreased by 69% [ OR (95% CI): 0.31 (0.10-0.92)]. Subgroup analysis of body composition indicators showed that the protective effect of normal CD4 cell level on physical frailty was more pronounced in the high skeletal muscle mass and high basal metabolic rate group ( Pinteraction<0.05). Conclusion:The prevalence of physical frailty among elderly HIV-infected patients is relatively lower in Chongqing, and the CD4 cell level, skeletal muscle mass and basal metabolic rate are related to physical frailty.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.