BACKGROUND:Obesity is not only related to metabolic diseases such as diabetes and cardiovascular disease,but also closely related to the increased risk of cognitive decline,dementia and other neurodegenerative diseases.Studies have found that aerobic exercise and resistance exercise can help improve obesity-related cognitive impairment,but their therapeutic effects and related mechanisms of action are still unclear.OBJECTIVE:To explore the protective effects of aerobic and resistance exercises on the nervous center of obesity-related cognitive impairment mice.METHODS:Forty-eight 8-week-old C57BL/6J wild-type male mice were randomly divided into four groups:a control group was fed normally for 20 weeks;a high fat group was fed with high fat diet(60％fat energy)for 20 weeks;an aerobic exercise group was fed with 12 weeks of high-fat diet followed by 8 weeks of aerobic exercise;and a resistance exercise group was fed with 12 weeks of high-fat diet followed by 8 weeks of resistance exercise.After the exercise intervention,body mass was weighed,insulin tolerance and glucose tolerance were tested to evaluate insulin resistance,and cognitive function of mice in each group was detected by new object recognition experiment and Y-maze experiment.The morphology of hippocampal and cortical tissue cells was observed by hematoxylin-eosin staining.The mRNA relative expression levels of tumor necrosis factor-α and interleukin-6 were detected by real-time fluorescence quantitative PCR,and the protein expressions of Bax,Bcl-2,nuclear factor-κB,Cleaved Caspase-1,Caspase-3,synapsin 1 and brain-derived neurotrophic factor were detected by western blot.RESULTS AND CONCLUSION:(1)Compared with the control group,the body mass of mice increased in the high-fat group(P＜0.05),accompanied by insulin resistance and cognitive dysfunction,the expression levels of nuclear factor-κB,Bax,Caspase-3,Cleaved Caspase-1 in the hippocampus were significantly increased(P＜0.05),the expression levels of brain-derived neurotrophic factor,synapsin 1and Bcl-2 proteins were significantly decreased(P＜0.05),Bcl-2/Bax ratio was significantly decreased(P＜0.05),and the mRNA levels of inflammatory cytokines,tumor necrosis factor-α and interleukin-6,were significantly up-regulated(P＜0.05).(2)Compared with the high-fat group,the above indexes were significantly improved in the aerobic exercise group(P＜0.05),while in the resistance exercise group,the body mass of mice was significantly decreased,the levels of inflammatory cytokines tumor necrosis factor-α and interleukin-6 mRNA were significantly decreased(P＜0.05),the protein expression of Caspase-3 was significantly decreased(P＜0.05),and the protein expression of brain-derived neurotrophic factor was significantly up-regulated(P＜0.05),but no significant changes were observed in the other indexes(P＞0.05).In conclusion,long-term exercise can reduce insulin resistance,down-regulate the expression of nuclear factor-κB pathway,weaken inflammatory response,inhibit neuronal apoptosis and improve synaptic plasticity,resulting in neuroprotective effects,and effectively alleviate obesity-related cognitive dysfunction in obese mice.The therapeutic effect of aerobic exercise is superior to that of resistance exercise.

BACKGROUND:Obesity is not only related to metabolic diseases such as diabetes and cardiovascular disease,but also closely related to the increased risk of cognitive decline,dementia and other neurodegenerative diseases.Studies have found that aerobic exercise and resistance exercise can help improve obesity-related cognitive impairment,but their therapeutic effects and related mechanisms of action are still unclear.OBJECTIVE:To explore the protective effects of aerobic and resistance exercises on the nervous center of obesity-related cognitive impairment mice.METHODS:Forty-eight 8-week-old C57BL/6J wild-type male mice were randomly divided into four groups:a control group was fed normally for 20 weeks;a high fat group was fed with high fat diet(60％fat energy)for 20 weeks;an aerobic exercise group was fed with 12 weeks of high-fat diet followed by 8 weeks of aerobic exercise;and a resistance exercise group was fed with 12 weeks of high-fat diet followed by 8 weeks of resistance exercise.After the exercise intervention,body mass was weighed,insulin tolerance and glucose tolerance were tested to evaluate insulin resistance,and cognitive function of mice in each group was detected by new object recognition experiment and Y-maze experiment.The morphology of hippocampal and cortical tissue cells was observed by hematoxylin-eosin staining.The mRNA relative expression levels of tumor necrosis factor-α and interleukin-6 were detected by real-time fluorescence quantitative PCR,and the protein expressions of Bax,Bcl-2,nuclear factor-κB,Cleaved Caspase-1,Caspase-3,synapsin 1 and brain-derived neurotrophic factor were detected by western blot.RESULTS AND CONCLUSION:(1)Compared with the control group,the body mass of mice increased in the high-fat group(P＜0.05),accompanied by insulin resistance and cognitive dysfunction,the expression levels of nuclear factor-κB,Bax,Caspase-3,Cleaved Caspase-1 in the hippocampus were significantly increased(P＜0.05),the expression levels of brain-derived neurotrophic factor,synapsin 1and Bcl-2 proteins were significantly decreased(P＜0.05),Bcl-2/Bax ratio was significantly decreased(P＜0.05),and the mRNA levels of inflammatory cytokines,tumor necrosis factor-α and interleukin-6,were significantly up-regulated(P＜0.05).(2)Compared with the high-fat group,the above indexes were significantly improved in the aerobic exercise group(P＜0.05),while in the resistance exercise group,the body mass of mice was significantly decreased,the levels of inflammatory cytokines tumor necrosis factor-α and interleukin-6 mRNA were significantly decreased(P＜0.05),the protein expression of Caspase-3 was significantly decreased(P＜0.05),and the protein expression of brain-derived neurotrophic factor was significantly up-regulated(P＜0.05),but no significant changes were observed in the other indexes(P＞0.05).In conclusion,long-term exercise can reduce insulin resistance,down-regulate the expression of nuclear factor-κB pathway,weaken inflammatory response,inhibit neuronal apoptosis and improve synaptic plasticity,resulting in neuroprotective effects,and effectively alleviate obesity-related cognitive dysfunction in obese mice.The therapeutic effect of aerobic exercise is superior to that of resistance exercise.

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

ObjectiveTo investigate the potential mechanism of heat-sensitive moxibustion on chronic atrophic gastritis （CAG） through the phosphoinositide 3-kinase/protein kinase B （PI3K/Akt） signaling pathway. MethodsFifty-eight SD rats were randomly divided into blank group （n=14） and modeling group （n=44）. Rats in the blank group were fed routinely， while the rats in the modeling group received drinking water containing 1-methyl-3-nitro-1-nitrosoguanidine （MNNG） at a concentration of 140 μg/ml， combined with irregular fasting and feeding for 12 weeks to establish CAG model. After successful modeling， the rats were randomly divided into model group （n=10）， inhibitor group （n=10） and moxibustion group （n=20）. After 40 minutes of suspended moxibustion at "Zhongwan" （CV 12） daily， the rats in the moxibustion group were divided into heat-sensitive moxibustion group （n=10） and non-heat-sensitive moxibustion group （n=9） according to the change of tail temperature during moxibustion. The inhibitor group was bound for 40 minutes daily， and then administered with PI3K/Akt signaling pathway inhibitor， rapamycin solution， by gavage at a dose of 1 mg/kg. The model group received intragastric administration of 1 ml/kg normal saline after 40 minutes of restraint stress each day. All interventions were administered once daily for 28 consecutive days， while the blank group received no intervention. After the intervention finished， the body weight of rats in each group was compared. HE staining was used to observe the histopathological changes of gastric mucosa. The apoptosis-positive rate of gastric mucosal cells was detected by TUNEL assay. Immunohistochemistry was performed to determine the protein levels of matric metalloproteinase-7 （MMP7）， vascular endothelial growth factor A （VEGFA） and epidermal growth factor receptor （EGFR） in gastric mucosa. The mRNA expression levels of PI3K， Akt and mammalian target of rapamycin （mTOR） in gastric mucosal tissues were detected by qPCR. The protein levels of phosphorylated Akt （p-Akt） and phosphorylated mTOR （p-mTOR） in rat gastric mucosal tissues were measured by Western Blotting. ResultsCompared to the blank group， rats in all other groups exhibited decreased body weight， significantly increased gastric mucosal cell apoptosis-positive rates， elevated protein levels of MMP7， VEGFA and EGFR in gastric mucosa， increased mRNA expression levels of PI3K， Akt and mTOR， and enhanced protein expression levels of p-Akt and p-mTOR （P＜0.05 or P＜0.01）. Histopathological examination revealed thinning of the gastric mucosa， glandular disorganization and atrophy， accompanied by intestinal metaplasia.Compared to the model group， the heat-sensitive moxibustion group， the non-heat-sensitive moxibustion group and the inhibitor group all showed significant improvements in the above-mentioned indicators （P＜0.05 or P＜0.01）. Compared to the heat-sensitive moxibustion group， the non-heat-sensitive moxibustion group and the inhibitor group exhibited increased positive rates of gastric mucosal cell apoptosis； the non-heat-sensitive moxibustion group showed increased protein levels of MMP7， VEGFA and EGFR， as well as mRNA expression levels of PI3K， Akt and mTOR， and protein expressions of p-Akt and p-mTOR； the inhibitor group exhibited elevated protein expression level of EGFR （P＜0.05 or P＜0.01）. Histopathological examination showed that the gastric mucosal glands in the heat-sensitive moxibustion group were arranged more regularly， with an approximately normal structural appearance. ConclusionHeat-sensitive moxibustion can improve the body weight of CAG rats and repair gastric mucosal injury. Its therapeutic effects may be mediated by inhibiting excessive activation of gastric mucosal PI3K/Akt signaling pathway， thereby reducing gastric mucosal cell apoptosis.

ObjectiveTo investigate the potential mechanism of heat-sensitive moxibustion on chronic atrophic gastritis （CAG） through the phosphoinositide 3-kinase/protein kinase B （PI3K/Akt） signaling pathway. MethodsFifty-eight SD rats were randomly divided into blank group （n=14） and modeling group （n=44）. Rats in the blank group were fed routinely， while the rats in the modeling group received drinking water containing 1-methyl-3-nitro-1-nitrosoguanidine （MNNG） at a concentration of 140 μg/ml， combined with irregular fasting and feeding for 12 weeks to establish CAG model. After successful modeling， the rats were randomly divided into model group （n=10）， inhibitor group （n=10） and moxibustion group （n=20）. After 40 minutes of suspended moxibustion at "Zhongwan" （CV 12） daily， the rats in the moxibustion group were divided into heat-sensitive moxibustion group （n=10） and non-heat-sensitive moxibustion group （n=9） according to the change of tail temperature during moxibustion. The inhibitor group was bound for 40 minutes daily， and then administered with PI3K/Akt signaling pathway inhibitor， rapamycin solution， by gavage at a dose of 1 mg/kg. The model group received intragastric administration of 1 ml/kg normal saline after 40 minutes of restraint stress each day. All interventions were administered once daily for 28 consecutive days， while the blank group received no intervention. After the intervention finished， the body weight of rats in each group was compared. HE staining was used to observe the histopathological changes of gastric mucosa. The apoptosis-positive rate of gastric mucosal cells was detected by TUNEL assay. Immunohistochemistry was performed to determine the protein levels of matric metalloproteinase-7 （MMP7）， vascular endothelial growth factor A （VEGFA） and epidermal growth factor receptor （EGFR） in gastric mucosa. The mRNA expression levels of PI3K， Akt and mammalian target of rapamycin （mTOR） in gastric mucosal tissues were detected by qPCR. The protein levels of phosphorylated Akt （p-Akt） and phosphorylated mTOR （p-mTOR） in rat gastric mucosal tissues were measured by Western Blotting. ResultsCompared to the blank group， rats in all other groups exhibited decreased body weight， significantly increased gastric mucosal cell apoptosis-positive rates， elevated protein levels of MMP7， VEGFA and EGFR in gastric mucosa， increased mRNA expression levels of PI3K， Akt and mTOR， and enhanced protein expression levels of p-Akt and p-mTOR （P＜0.05 or P＜0.01）. Histopathological examination revealed thinning of the gastric mucosa， glandular disorganization and atrophy， accompanied by intestinal metaplasia.Compared to the model group， the heat-sensitive moxibustion group， the non-heat-sensitive moxibustion group and the inhibitor group all showed significant improvements in the above-mentioned indicators （P＜0.05 or P＜0.01）. Compared to the heat-sensitive moxibustion group， the non-heat-sensitive moxibustion group and the inhibitor group exhibited increased positive rates of gastric mucosal cell apoptosis； the non-heat-sensitive moxibustion group showed increased protein levels of MMP7， VEGFA and EGFR， as well as mRNA expression levels of PI3K， Akt and mTOR， and protein expressions of p-Akt and p-mTOR； the inhibitor group exhibited elevated protein expression level of EGFR （P＜0.05 or P＜0.01）. Histopathological examination showed that the gastric mucosal glands in the heat-sensitive moxibustion group were arranged more regularly， with an approximately normal structural appearance. ConclusionHeat-sensitive moxibustion can improve the body weight of CAG rats and repair gastric mucosal injury. Its therapeutic effects may be mediated by inhibiting excessive activation of gastric mucosal PI3K/Akt signaling pathway， thereby reducing gastric mucosal cell apoptosis.

ObjectiveTo evaluate the clinical efficacy and safety of the Qishen Liuwei presoription for senile hypertension complicated with frailty （of Qi deficiency and blood stasis pattern， or deficiency of both spleen and kidney pattern）. MethodsA single-center， randomized controlled clinical trial design was employed in this study. Sixty-four eligible patients， treated at the Cardiology Outpatient Clinic of Dongfang Hospital， Beijing University of Chinese Medicine between June 2024 and February 2025， were randomly allocated into an observation group or a control group， with 32 patients in each group. Both groups received standard conventional antihypertensive therapy， while the observation group additionally received the Qishen Liuwei Formula （one dose per day， in separate servings in the morning and evening）. For both groups， a treatment course consisted of 4 weeks， followed by a 2-month follow-up period. Then， the primary indicator （Fried frailty phenotype scores）， along with secondary indicators including traditional Chinese medicine （TCM） syndrome scores and changes in blood pressure were observed before and after treatment. ResultsRegarding Fried frailty phenotype scores， the observation group exhibited significantly improved grip strength， 4.57 m walk time， the duration of weekly walks， ''effort required for any activity''， and ''inability to walk forward'' after treatment， while only the latter two indicators were significantly improved in the control group （P<0.05）. Compared with the control group， the observation group demonstrated significantly superior improvement in the duration of weekly walks， ''effort required for any activity''， and frailty （P<0.05）. For total TCM syndrome scores， both groups displayed significantly decreased total TCM syndrome scores （P<0.05） after treatment， and the decrease was more significant in the observation group （P<0.05）. Regarding office blood pressure， both groups showed significantly decreased diastolic blood pressure and mean arterial pressure after treatment， while the observation group also showed significantly decreased systolic blood pressure （P<0.05）. During treatment， one case of facial rash occurred in the observation group， representing an adverse reaction rate of 3.13% （1/32）. The rash resolved one week after discontinuation of medication. No adverse reactions occurred in the control group during treatment. No statistically significant difference was observed in the incidence of adverse reactions between the two groups. ConclusionFor senile hypertension complicated with frailty， the Qishen Liuwei presoription effectively improves physical activity， muscle strength， frailty-related symptoms， and TCM syndrome remission. When combined with Western medicine， the Formula contributes to stable blood pressure control and demonstrates a favorable clinical safety profile， indicating its clinical application potential.

ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.

ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

Objective: To investigate the distribution patterns and risk factors for multidrug-resistant bacterial pulmonary infections in patients with oral squamous cell carcinoma (OSCC) undergoing flap reconstruction surgery, and to provide evidence for infection prevention and treatment in this population. Methods: This study was approved by the institutional medical ethics committee. We retrospectively analyzed sputum culture results, antimicrobial susceptibility testing data, and clinical records of 109 OSCC patients undergoing flap reconstruction. Chi-square tests were employed to identify pathogens and risk factors for multidrug-resistant bacteria (MDR) in postoperative pulmonary infections. Multivariate logistic regression analysis was conducted to determine MDR risk factors and establish a nomogram prediction model. The model’s discriminatory power, accuracy, and clinical utility were evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results: Among the 109 patients, 52 had negative sputum cultures and 57 tested positive, of whom 14 developed multidrug-resistant (MDR) pulmonary infections. Chi-square analysis revealed that blood transfusion, pre-existing pulmonary diseases, operation time ≥ 490 min, intraoperative blood loss ≥ 400 mL, and abnormal BMI were significant risk factors for postoperative MDR infections (P < 0.05). Multivariate logistic regression identified pre-existing pulmonary diseases, intraoperative blood loss ≥ 400 mL, abnormal BMI, and operative duration ≥ 490 min as independent risk factors for MDR infections (P < 0.05). The nomogram prediction model for MDR infections demonstrated an area under the ROC curve (AUC) of 0.874 (95% CI: 0.775-0.973). The calibration plot showed good agreement between predicted and observed outcomes. DCA indicated a net clinical benefit when the threshold probability for high-risk MDR infections ranged from 0.000 to 0.810. Common MDR pathogens included MDR Pseudomonas aeruginosa, MDR Klebsiella pneumoniae, carbapenem-resistant Acinetobacter baumannii (CRAB), and methicillin-resistant Staphylococcus aureus (MRSA). Conclusion Among OSCC patients undergoing flap reconstruction, MDR pulmonary infections were predominantly caused by gram-negative bacteria (including CRAB, MDR Pseudomonas aeruginosa, and MDR Klebsiella pneumoniae along with the gram-positive pathogen MRSA. Pre-existing pulmonary comorbidities, prolonged surgery duration (≥ 490 min), significant intraoperative blood loss (≥ 400 mL), and abnormal BMI were confirmed as independent risk factors for these MDR infections. The nomogram predictive model incorporating these four variables demonstrated clinically reliable accuracy in risk stratification for postoperative MDR pulmonary infections in this patient population.

Objective To investigate the independent risk factors affecting the prognosis of chronic active antibody-mediated rejection (caAMR) after kidney transplantation. Methods A retrospective analysis was conducted on 61 patients who underwent renal biopsy and were diagnosed with caAMR. The patients were divided into caAMR group (n=41) and caAMR+TCMR group (n=20) based on the presence or absence of concurrent acute T cell-mediated rejection (TCMR). The patients were followed up for 3 years. The value of 24-hour urinary protein and estimated glomerular filtration rate (eGFR) at the time of biopsy in predicting graft loss was assessed using receiver operating characteristic (ROC) curves. The independent risk factors affecting caAMR prognosis were analyzed using the LASSO-Cox regression model. The correlation between grouping, outcomes, and Banff scores was compared using Spearman rank correlation matrix analysis. Kaplan-Meier analysis was used to evaluate the renal allograft survival rates of each subgroup. Results The 3-year renal allograft survival rates for the caAMR group and the caAMR+TCMR group were 83% and 79%, respectively. The area under the ROC curve (AUC) for predicting 3-year renal allograft loss was 0.83 ［95% confidence interval (CI) 0.70-0.97］ for eGFR and 0.78 (95% CI 0.61-0.96) for 24-hour urinary protein at the time of biopsy. LASSO-Cox regression analysis and Kaplan-Meier analysis showed that eGFR≤25.23 mL/(min·1.73 m²) and the presence of donor-specific antibody (DSA) against human leukocyte antigen (HLA) class I might be independent risk factors affecting renal allograft prognosis, with hazard ratios of 7.67 (95% CI 2.18-27.02) and 5.13 (95% CI 1.33-19.80), respectively. A strong correlation was found between the Banff chronic lesion indicators of renal interstitial fibrosis and tubular atrophy (P<0.05). Conclusions The presence of HLA class I DSA and eGFR≤25.23 mL/(min·1.73 m²) at the time of biopsy may be independent risk factors affecting the prognosis of caAMR.