Organ transplantation is an effective alternative treatment for patients with end-stage organ failure. However, the shortage of donor organs has limited the widespread application of clinical transplantation. In recent years, breakthroughs in CRISPR-Cas9 gene editing technology have overcome the barrier of hyperacute rejection in xenotransplantation, offering a potential solution to the organ shortage crisis. Rejection remains a critical factor affecting graft survival. Antigen-presenting cells play a vital role in the initiation and progression of rejection and immune regulation in xenotransplantation. Therefore, in-depth investigation into the role of antigen-presenting cells in xenotransplantation is of great significance. This article summarizes the roles and therapeutic strategies of professional antigen-presenting cells, including macrophages, dendritic cells and B cells in xenotransplantation, aiming to provide insights for future research on immune regulation mechanisms in this field.

OBJECTIVE To study the improvement effect and mechanism of Tripterygium wilfordii multiglucoside （TWM） on nephrotic syndrome in rats. METHODS The nephrotic syndrome model was established by intravenous injection of adriamycin via the tail vein. The modeling rats were randomly divided into the model group （distilled water）， prednisone group （10 mg/kg）， and TWM high- and low-dose groups （10 and 5 mg/kg， respectively）. Additionally， blank group （distilled water） without model induction was established. Each group consisted of 9 rats. Rats in each group were administered the corresponding drugs or distilled water by gavage， once a day， for 6 consecutive weeks. The histopathological morphology of kidney tissues in rats was observed； the levels of 24-hour urinary protein （24 h-UTP） and serum biochemical indicators [albumin （ALB）， blood urea nitrogen （BUN）， serum creatinine （SCr）， cholesterol （CHOL）， and triglyceride （TG）] in rats were determined； the levels of oxidative stress indicators [superoxide dismutase （SOD）， malondialdehyde （MDA）] in kidney tissue of rats were determined； expressions of hypoxia-inducible factor-1α （HIF-1α）/microRNA-155-5p （miR-155-5p）/nuclear factor erythriod 2- related factor 2 （Nrf2） signaling pathway-related mRNA and protein in the renal tissues of rats were detected. RESULTS Compared with the blank group， the rats in the model group exhibited disordered renal tissue structure， with a small amount of glomerular necrosis and edema of the renal tubular epithelial cells. 24 h-UTP， serum levels of SCr， BUN， CHOL and TG， MDA content， mRNA and protein expressions of HIF-1α and Keap1 as well as the expression of miR-155-5p in renal tissues were increased significantly （ P ＜0.05）. Serum level of ALB， SOD level in renal tissue as well as mRNA and protein expressions of Nrf2 were decreased significantly （ P ＜0.05）. Compared with the model group， TWM high-dose and low-dose groups exhibited significant improvements in renal injury， with notable reversals in the levels of the above quantitative indicators （ P ＜0.05）. CONCLUSIONS TWM can alleviate oxidative stress-induced damage and thereby improve nephrotic syndrome in rats by regulating the HIF-1α/miR-155-5p/Nrf2 signaling pathway.

OBJECTIVE: To observe the efficacy of successive trigger needling combined with conventional acupuncture for cervical spondylosis of qi stagnation and blood stasis. METHODS: A total of 40 patients with cervical spondylosis of qi stagnation and blood stasis were selected, and successive trigger needling at ashi points combined with conventional acupuncture at Baihui (GV20) and bilateral C₃-C₇ Jiaji (EX-B2), Jiquan (HT1), etc. were delivered, once a day, 5 times a week as one course, and 2 courses were required totally. Before treatment and after 1, 2 weeks of treatment, the pain visual analogue scale (VAS) score was observed, and the clinical efficacy was evaluated after treatment. RESULTS: After 1, 2 weeks of treatment, the VAS scores were decreased compared with that before treatment (P<0.001). After treatment, the total effective rate was 97.5% (39/40). CONCLUSION Successive trigger needling combined with conventional acupuncture can effectively treat the cervical spondylosis of qi stagnation and blood stasis, reduce pain and improve the clinical symptoms and signs.
Humans ; Spondylosis/physiopathology* ; Male ; Acupuncture Therapy ; Female ; Middle Aged ; Adult ; Qi ; Aged ; Acupuncture Points ; Treatment Outcome ; Combined Modality Therapy

BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

OBJECTIVE To investigate the renal protective effect and mechanism of Shenbining granule on IgA nephropathy （IgAN） rats by regulating the CXC chemokine motif ligand 12 （CXCL12）/CXC chemokine receptor 4 （CXCR4）/signal transducer and activator of transcription 3 （STAT3） signaling pathway. METHODS A total of 60 rats were randomly assigned into blank group （n＝12） and modeling group （n＝48）. IgAN model of modeling group was induced by using bovine serum albumin， carbon tetrachloride and lipopolysaccharide， followed by model validation. Ultimately， a total of 55 rats （9 in the blank group， 46 in the modeling group） were included in the subsequent study. The rats in the modeling group were randomly divided into model group （n＝10）， prednisone acetate group [positive control group， 6.25 mg/（kg·d）， n＝12]， Shenbining granule low- and high-dose groups [4.17， 8.33 g/（kg·d）， n＝12]. They were given relevant medicine/distilled water intragastrically， once a day， for 4 consecutive weeks. After the last medication， biochemical indicators in the urine and serum of rats were measured， and pathological morphological changes in the renal tissues of rats were observed. IgA deposition in the renal tissues， as well as the mRNA expression levels of CXCL12， CXCR4 and STAT3， and the protein expression levels of CXCL12， CXCR4， STAT3 and phosphorylated STAT3 （p-STAT3） were detected. Additionally， the level of interleukin-6 （IL-6） in the renal tissue was measured. RESULTS Compared with the model group， the low-dose and high-dose Shenbining granule groups showed significantly decreased urinary red blood cell count， 24 h total urinary protein， blood urea nitrogen， serum creatinine， and alanine amino-transferase， along with increased Alb levels （P＜0.05）. Pathological damage in the renal tissues was alleviated， with reduced IgA deposition in the mesangial region （P＜0.05）； protein and mRNA expressions of CXCL12， CXCR4 and STAT3， as well as phosphorylation level of STAT3 protein and the IL-6 level， were significantly decreased in renal tissue （P＜0.05）. CONCLUSIONS Shenbining granule may exert its renal protective effects in IgAN rats by inhibiting the activation of the CXCL12/ CXCR4/STAT3 signaling pathway， downregulating the expression of inflammatory factors such as IL-6， alleviating renal inflammation， and thereby improving renal pathological damage.

OBJECTIVES: To explore the mechanism of Shenqi Buzhong (SQBZ) Formula for alleviating mitochondrial dysfunction in a rat model of chronic obstructive pulmonary disease (COPD) in light of the AMPK/SIRT1/PGC-1α pathway. METHODS: Fifty male SD rat models of COPD, established by intratracheal lipopolysaccharide (LPS) instillation, exposure to cigarette smoke, and gavage of Senna leaf infusion, were randomized into 5 groups (n=10) for treatment with saline (model group), SQBZ Formula at low, moderate and high doses (3.08, 6.16 and 12.32 g/kg, respectively), or aminophylline (0.024 g/kg) by gavage for 4 weeks, with another 10 untreated rats as the control group. Pulmonary function of the rats were tested, and pathologies and ultrastructural changes of the lung tissues were examined using HE staining and transmission electron microscopy. The levels of SOD, ATP, MDA, and mitochondrial membrane potential in the lungs were detected using WST-1, colorimetric assay, TBA, and JC-1 methods. Flow cytometry was used to analyze ROS level in the lung tissues, and the protein expression levels of P-AMPKα, AMPKα, SIRTI, and PGC-1α were detected using Western blotting. RESULTS: The rat models of COPD showed significantly decreased lung function, severe histopathological injuries of the lungs, decreased pulmonary levels of SOD activity, ATP and mitochondrial membrane potential, increased levels of MDA and ROS, and decreased pulmonary expressions of P-AMPKα, SIRTI, and PGC-1α proteins. All these changes were significantly alleviated by treatment with SQBZ Formula and aminophylline, and the efficacy was comparable between high-dose SQBZ Formula group and aminophylline group. CONCLUSIONS SQBZ Formula ameliorates mitochondrial dysfunction in COPD rats possibly by activating the AMPK/SIRT1/PGC-1α pathway.
Animals ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Sirtuin 1/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Rats, Sprague-Dawley ; Male ; Rats ; AMP-Activated Protein Kinases/metabolism* ; Mitochondria/metabolism* ; Disease Models, Animal ; Signal Transduction/drug effects*

Objective:To analyze the clinical characteristics, treatment options, and prognosis of intranasal reactive hemangioma associated with camrelizumab therapy.Methods:Clinical data from patients with intranasal reactive hemangioma associated with camrelizumab treated at Nanfang Hospital of Southern Medical University from February 2021 to April 2022 were collected, including patients′ demographics, clinical symptoms, endoscopic lesion characteristics, enhanced MRI results of the sinuses, pathological examination results, treatment plans, and disease outcomes at the last follow-up.Results:A total of 5 patients with intranasal reactive hemangioma were included, comprising 3 males and 2 females, with ages ranging from 21 to 61 years. The primary diseases of these patients included advanced primary liver cancer and nasopharyngeal carcinoma with liver and lung metastases. All patients presented with recurrent nasal bleeding and progressively worsening nasal obstruction, rated as grade 2 adverse reactions. The onset of intranasal reactive hemangioma was observed after 2 to 15 cycles of camrelizumab injections, with lesions primarily located in the common nasal passage and nasopharynx. Endoscopically, intranasal reactive hemangiomas appeared as dark red, narrow-based, and easily bleeding tumor-like lesions. Enhanced MRI showed mild to moderate heterogeneous enhancement. All patients underwent endoscopic resection of hemangioma via a lesion-targeted technique, with the surgical procedure confined to the removal of the grossly visible tumor mass and 5 mm surrounding mucosal margins around the tumor bed. Postoperative pathological examination revealed hemangioma characteristics, including variably sized vascular lumens and endothelial cell proliferation. Follow-up duration ranged from 6 to 12 months, during which none of the patients experienced recurrence of intranasal reactive hemangioma.Conclusion:Prompt surgical excision of camrelizumab-induced intranasal reactive hemangioma is recommended upon diagnosis to mitigate bleeding complications.

Objective:To investigate the clinicopathological features of SMARCA4-deficient uterine sarcoma.Methods:Five cases of SMARCA4-deficient uterine sarcoma at the Department of Pathology, the First Affiliated Hospital of Nanjing Medical University from 2018 to 2024 were collected. The morphological and immunohistochemical features were observed and analyzed. A follow-up study was also carried out.Results:Five female patients, aged 24, 54, 56, 61, and 41 years, respectively, presented with vaginal bleeding or abdominal pain. All patients had imaging findings of intracavitary lesion in the uterus, with tumor sizes ranging from 3.0 cm to 8.8 cm. The patients were followed up for 2 to 14 months. Case 1 died 9 months after surgery, whereas the remaining four patients were still alive. Histologically, the tumor cells exhibited a diffuse growth pattern, with an infiltration depth involving more than half of the myometrium. Portions of the interstitium appeared sclerosed. Benign endometrial glandular structures were observed in a leaf-like or fissured pattern, resembling those of uterine adenosarcoma. The tumor cells were large epithelioid with abundant or faintly eosinophilic cytoplasm, and the nuclei were moderately to markedly atypia with prominent nucleoli and brisk mitosis. Rhabdoid cells were seen. Some areas showed small round blue cells, with occasional spindle cells and myxoid stroma. Additionally, widespread or focal lymphovascular space invasion was observed within the myometrium. All five cases exhibited absence of SMARCA4 (BRG1) expression and retained SMARCB1 (INI1). Claudin4 expression was negative. There was no deficient expression of mismatch repair proteins MLH1, PMS2, MSH2 and MSH6. p53 showed wild-type expression. Ki-67 index ranged from 30% to 60%. CKpan, CK7, ER, PR, and PAX8 were negative.Conclusions:SMARCA4-deficient uterine sarcoma is rare, highly aggressive, and has a poor prognosis. The tumor exhibits a broad morphological spectrum, with rhabdoid cells and adenosarcoma-like structures serving as important diagnostic clues. The absence of BRG1 expression lends support to a definitive diagnosis.

Objective:To evaluate the efficacy of the flipped classroom combined with 3D body anatomy software in the teaching of ultrasound-guided transversus thoracic muscle plane block.Methods:In this randomized controlled trial, 100 second-year resident physicians from the Department of Anesthesiology and Perioperative Medicine at our hospital, male or female, aged 22-26 yr, who rotated during January 2023 to January 2025, were selected and divided into 2 groups ( n=50 each) using a table of random numbers: experimental group and control group. Experimental group employed the teaching model of flipped classroom combined with 3D body anatomy software, while control group used the traditional teaching model. The scores of theoretical assessment, accuracy rate of ultrasound image identification, scores of procedural skills, success rates of clinical procedure, teaching satisfaction, and success rates of clinical translation after 1 month follow-up were compared between two groups. Results:Compared with control group, the scores of theoretical assessment, accuracy rate of ultrasound image identification, scores of procedural skills, success rates of clinical procedure, teaching satisfaction, and success rates of clinical translation after 1 month follow-up were significantly increased in experimental group ( P<0.05). Conclusions:The combination of flipped classroom and 3D body anatomy software is more effective than the traditional teaching methods when used for teaching of ultrasound-guided transversus thoracic muscle plane block.

Objective:To screen the optimal machine learning model for predicting the recurrence condition of hepatocellular carcinoma (HCC) at different time points post-surgery, based on the cutoff value of the Ki67 positive proliferation index condition calculated from recurrence-free survival and combined with various clinical features.Methods:retrospective study included initially treated patients with solitary HCC who underwent radical surgery at the Fifth Medical Center of the PLA General Hospital from January 2013 to March 2023. Data included general clinical data, preoperative laboratory parameters, and surgical pathology information about the subjects. The postoperative recurrence status was assessed by querying the medical record system or by telephone follow-up. The Ki67 positive index cutoff value was determined by the X-tile software based on the patient's recurrence-free survival status and time analysis. Survival rates were calculated using the Kaplan-Meier method, and survival curves were plotted. The study population was randomly divided into training and testing groups in a 7:3 ratio using a computer-generated random number method. The minimum redundancy maximum relevance (mRMR) method was used for feature variable selection. Predictive models for postoperative HCC recurrence conditions in patients with HCC were constructed using random forest, support vector machine, logistic regression, and gradient boosting decision tree machine learning algorithms. Inter-group comparisons for continuous data were performed using the t-test or Mann-Whitney U test. Inter-group comparisons of enumeration data were performed using the Pearson χ2 test, continuity-corrected χ2 test, or Fisher's exact test. Results:The cutoff values for the Ki67 positivity index were 0.3 and 0.5 in 510 cases, with a follow-up time ranging from 1.2 to 11.4 years (median: 6.2 years). The recurrence-free survival time was between 1 and 135 months (median: 32 months), with recurrence-free survival rates post-surgery at 1, 2, 3, and 5 years were 87.5%, 77.1%, 61.2%, and 54.5%, respectively. The top five variables predicted HCC recurrence and non-recurrence conditions following surgical follow-up at 6 months, 1 year, 2 years, and beyond 2 years, in accordance with information obtained by the mRMR screen out. The Ki67 positivity index screened a successfully constructed machine learning model to predict HCC recurrence and non-recurrence conditions following surgical follow-up at 6 months, 1 year, 2 years, and beyond 2 years. The machine learning model based on the gradient boosting decision tree algorithm had the best prediction performance among them (areas under the receiver operating characteristic curves for predicting HCC recurrence within six months in the training and validation sets were 0.996 and 0.946, and accuracies were 0.972 and 0.935, respectively).Conclusion:A machine learning model was successfully constructed using the Ki67 positivity index combined with four readily available clinical features to predict HCC recurrence. The machine learning model based on the gradient boosting decision tree algorithm demonstrated the best performance in terms of predicting HCC recurrence within six months after surgery.