1.Clinical efficacy of therapeutic whole blood exchange combined with lymphoplasmapheresis in refractory autoimmune hemolytic anemia
Gang WANG ; Yixin GAO ; Linyan WU ; Liuyan PAN ; Suying HE ; Lijuan ZHOU ; Yongzheng PENG ; Minghui YANG
Chinese Journal of Blood Transfusion 2025;38(10):1348-1354
Objective: To evaluate the safety and efficacy of therapeutic whole blood exchange combined with lymphoplasmapheresis in the treatment of refractory autoimmune hemolytic anemia (AIHA). Methods: A retrospective analysis was performed on the clinical data of AIHA patients who underwent therapeutic whole blood exchange combined with lymphoplasmapheresis at our hospital from March 2022 to May 2025. Efficacy was assessed by comparing changes in hemoglobin, platelet count, and bilirubin levels before and after treatment. Safety was evaluated by analyzing vital signs before and after the procedure, parameters during the exchange, and adverse reactions. Results: A total of 12 AIHA patients were enrolled, completing 19 exchange procedures. The number of procedures per patient ranged from 1 to 3. The median treatment duration was 67 (65-73) minutes, with a median exchange volume of 2 025 (1 851-2 121) mL, comprising 4.5 (4-6) units of red blood cells and 1 350 (1 200-1 400) mL of plasma. Ten patients achieved partial remission, one achieved complete remission, and one showed no response, yielding an response rate of 91% (11/12). After a single session, hemoglobin increased significantly by 17.58±9.85 g/L (P<0.01), while platelets counts decreased by 45 (17.5, 79)×10
/L (P<0.05), and both systolic and diastolic blood pressure showed a significant elevation (P<0.05). However, no statistically significant differences were observed in total bilirubin, indirect bilirubin, white blood cell count, or heart rate. During the procedures, 4 adverse reactions occurred in 3 patients: one child experienced severe heart rate fluctuation twice consecutively, and two adults developed plasma allergies. All reactions resolved spontaneously without pharmacological intervention. Conclusion: The combination of therapeutic whole blood exchange and lymphoplasmapheresis appears to be a safe and effective treatment for refractory AIHA patients.
2.Efficacy and safety of immune checkpoint inhibitors in the treatment of recurrent or metastatic nasopharyngeal carcinoma: A systematic review and meta-analysis.
Zhixin YU ; Shaodong HONG ; Hui YU ; Xuanye ZHANG ; Zichun LI ; Ping CHEN ; Yixin ZHOU
Chinese Medical Journal 2025;138(5):531-539
BACKGROUND:
The combination of immune checkpoint inhibitors and chemotherapy (ICI + Chemo) shows promise in treatment of recurrent or metastatic nasopharyngeal carcinoma (RM-NPC), but some patients received limited benefit and the prognostic factors of the treatments remain unclear. Furthermore, ICIs efficacy in subsequent treatments needs further evaluation.
METHODS:
A systematic search on PubMed, Embase, the Cochrane Library, and major conference proceedings was conducted to identify relevant studies for meta-analysis. The study was designed to compare ICI + Chemo with chemotherapy in first-line treatment and identify efficacy predictors, and to evaluate ICIs alone in subsequent-line treatment for RM-NPC, with a focus on progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (AEs).
RESULTS:
Fifteen trials involving 1928 patients were included. Three trials compared ICI + Chemo with chemotherapy as a first-line treatment, while 12 trials evaluated ICIs alone in subsequent-line treatment of RM-NPC patients. First-line ICI + Chemo showed superior PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.43-0.63; P <0.001) and ORR (risk ratio [RR] = 1.14, 95% CI, 1.05-1.24; P <0.001) compared to chemotherapy, without increased AEs (RR = 1.01, 95% CI, 0.99-1.03; P = 0.481). Neither programmed death-ligand 1 (PD-L1) nor other factors predicted the efficacy of ICI + Chemo vs . chemotherapy. Subsequent-line ICIs alone had a median PFS of 4.12 months (95% CI, 2.93-5.31 months), an ORR of 24% (95% CI, 20-28%), with grade 1-5/grade 3-5 AEs at 79%/14%. However, ICIs alone were associated with significantly shorter PFS (HR = 1.31, 95% CI, 1.01-1.68; P = 0.040) than chemotherapy alone.
CONCLUSIONS
ICI + Chemo confers superior survival benefits compared to chemotherapy in first-line RM-NPC treatment, independent of PD-L1 expression or other factors. However, ICIs alone demonstrate a manageable safety profile but do not surpass chemotherapy in efficacy for subsequent-line treatment.
Humans
;
Immune Checkpoint Inhibitors/adverse effects*
;
Nasopharyngeal Carcinoma/drug therapy*
;
Nasopharyngeal Neoplasms/drug therapy*
;
Neoplasm Recurrence, Local/drug therapy*
3.Enhanced workflow applied in robotic-assisted total hip revision arthroplasty
Yixin ZHOU ; Wang DENG ; Yongqi XIA ; Kaiding WU ; Jinqing ZHANG ; Dejin YANG
Chinese Journal of Orthopaedic Trauma 2025;27(6):473-478
Objective:To evaluate the clinical outcomes of applying an enhanced workflow in robotic-assisted total hip revision arthroplasty.Methods:A retrospective study was conducted to analyze the 25 consecutive patients who had undergone robotic-assisted total hip revision arthroplasty in which an enhanced workflow was applied at Department of Orthopaedic Surgery, Beijing Jishuitan Hospital from September 2021 to October 2024. The cohort consisted of 8 males and 17 females with an age of (64.0±12.8) years. The left side was affected in 18 cases and the right side in 7 cases. The time from initial total hip arthroplasty to revision was (159.6±86.7) months. In all patients, no significant difference was found in the preoperative femoral cortical thickness between the healthy and the affected sides. The enhanced workflow included preoperative CT modeling and planning, intraoperative registration, prosthetic removal and reconstruction, and verification of prosthesis position. A total of 18 patients underwent total hip revision involving both the acetabular and the femoral sides; 6 patients underwent simple acetabular reconstruction with retention of the original femoral stem and replacement of the femoral head; 1 patient underwent femoral revision with retention of the acetabular cup and replacement of the acetabular liner. The operative time, intraoperative blood loss, modified Harris Hip Score (mHHS) and visual analogue scale (VAS) for hip pain at the final follow-up, and follow-up complications were recorded.Results:All patients successfully completed robotic registration during surgery, with no case of intraoperative robotic termination. For the 25 patients, the operative time was (152.2±43.8) minutes, the intraoperative blood loss 600 (400, 1,000) mL, and the follow-up time 12.0 (6.0, 31.5) months. At the final follow-up, their mHHS improved from 66.0 (26.4, 75.6) points preoperatively to 93.5 (80.3, 98.9) points, and their VAS pain score decreased from 5.0 (3.0, 7.0) points preoperatively to 0.0 (0.0, 2.0) point ( P<0.05). Follow-ups revealed no case of reoperation, prosthetic loosening, joint dislocation, periprosthetic infection, or periprosthetic fracture. Conclusion:The enhanced workflow can achieve satisfactory outcomes in robotic-assisted total hip revision for patients with adequate proximal femoral bone stock.
4.Clinical characterization of seven cases of sporadic Creutzfeldt-Jakob disease
Pankui LI ; Le CHANG ; Tingting YANG ; Jing ZHOU ; Yixin GU ; Zhenhai WANG
Chinese Journal of Experimental and Clinical Virology 2025;39(3):366-369
Objective:To analyze the clinical data of seven patients with a clinical diagnosis of likely sporadic Creutzfeldt-Jakob disease (sCJD) in order to improve the understanding and diagnosis of sporadic Creutzfeldt-Jakob disease.Methods:The clinical data of 7 sCJD patients admitted to the Department of Neurology of Our Hospital from 2021 to 2023 were retrospectively analyzed.Results:All seven patients had a subacute onset of disease, and the main clinical features included rapidly progressive dementia (RPD), cerebellar symptoms, pyramidal signs, myoclonus and akinetic mutism. Magnetic resonance diffusion-weighted imaging (DWI) reveals widespread asymmetrical lace-like high signal distributed along the cortex and a basal curved ball-and-stick sign. Electroencephalography (EEG) shows diffuse spiking and spiking slow waves, and periodic triphasic waves in advanced stages of the disease. Cerebrospinal fluid 14-3-3 protein testing was performed in 6 of the 7 patients, and 4 were positive. Four patients died within six months of onset of illness.Conclusions:The disease is prevalent in middle-aged and elderly patients, with a non-significant male-to-female ratio, and is dominated by the presence of Rapidly Progressive Dementia (RPD), especially the presence of cortical high signals in the DWI sequences and diffuse sharp and slow wave issuance in the electroencephalograph (EEG), which need to be alerted to the occurrence of Creutzfeldt-Jakob Disease. Dynamic review of MRI, EEG, cerebrospinal fluid 14-3-3 protein, prion protein gene (PRNP) sequence analysis and cerebrospinal fluid prion real-time vibration-induced protein amplification (RT-QuIC) monitoring whenever possible to avoid misdiagnosis, under-diagnosis, and under-recognition.
5.A single-center analysis of the short-term efficacy and safety of RAPN in 45 patients with non-metastatic pT 3a renal cell carcinoma
Xiangpeng ZOU ; Yunhan LUO ; Zhiling ZHANG ; Zhaohui ZHOU ; Longbin XIONG ; Yulu PENG ; Yixin HUANG ; Xin LUO ; Wensu WEI ; Zhenhua LIU ; Pei DONG ; Shengjie GUO ; Hui HAN ; Fangjian ZHOU
Chinese Journal of Urology 2025;46(5):369-375
Objective:To analyze the short-term efficacy and safety of robot-assisted laparoscopic partial nephrectomy(RAPN)for non-metastatic pathological stage T 3a renal cell carcinoma. Methods:The clinical and pathological data of 45 patients with pathologically confirmed non-metastatic T 3a renal cell carcinoma who underwent RAPN at Sun Yat-sen University Cancer Center between January 2016 and December 2023 were retrospectively reviewed. There were 30 males and 15 females. The average age of the cohort was(54.3±10.7)years,and the average clinical tumor diameter was(4.9±1.8)cm. Of all the patients,35(77.8%)were asymptomatic,7(15.6%)presented with hematuria,and 3(6.7%)presented with lumbar pain. Preoperative imaging assessed 34 patients(75.6%)as having clinical stage T 3a,all suspected of involving the collecting system or perirenal fat invasion;the remaining 11 patients(24.4%)were assessed as having stage T 1-2 disease. The median R.E.N.A.L. nephrectomy score was 8.0(7.0,10.0). A history of hypertension,diabetes,or chronic kidney disease was present in 18 patients(40.0%). The primary endpoint was progression-free survival,and the secondary endpoints included postoperative complications and short-term renal function outcomes. Survival curve was estimated using the Kaplan-Meier method,and renal function comparisons were made using the paired t-test. Results:The RAPN was performed through a transabdominal approach in 32 patients(71.1%),with a median estimated blood loss of 150.0(50.0,300.0)ml. Seven(15.6%)patients required intraoperative blood transfusion. The median length of postoperative hospital stay was 4.0(4.0,6.0)days. Postoperative complications occurred in 6 patients(13.3%),including 5(11.1%)with mild complications and 1(2.2%)with a severe complication. Renal function returned to baseline in 24 of 39 evaluable patients(61.5%),while 3 patients(7.7%)developed surgery-related chronic kidney disease 3 to 12 months postoperatively,but none required dialysis. The median follow-up time was 31.8(22.7,50.9)months,12(26.7%)patients received programmed cell death protein 1 inhibitor adjuvant therapy postoperatively. During follow-up,3 patients experienced tumor recurrence,the 3-year progression-free survival rate of the entire cohort was 95.4%.Conclusions:For some carefully selected patients with T 3a renal cell carcinoma,RAPN performed by experienced surgeons is a feasible and safe option,providing excellent short-term oncological outcomes,complication control,and renal function recovery. The long-term efficacy remains to be seen.
6.VDAC1 activates the PI3K/AKT/mTOR pathway to promote epithelial-mesenchymal transition and cell proliferation in lung adenocarcinoma
Yingru XING ; Ying ZHANG ; Yixin SU ; Yafeng LIU ; Jiawei ZHOU ; Feng ZHAO
Chinese Journal of Preventive Medicine 2025;59(3):317-327
Objective:To explore the regulatory mechanism of voltage-dependent anion channel 1(VDAC1) on the proliferation, migration and invasion of lung adenocarcinoma(LUAD) cells.Methods:This study employed a combination of bioinformatics and experimental validation methods, conducting bioinformatics analysis and cytological experimental validation in the central laboratory of the School of Medicine, Anhui University of Science and Technology from February 2023 to August 2024.Clinical histological specimen validation was performed using immunohistochemistry, and a retrospective analysis was conducted on 5 cases of lung adenocarcinoma and adjacent samples from Huai′an First People′s Hospital affiliated with Nanjing Medical University. The TCGA network database was analyzed for the expression pattern, prognostic value, and functional enrichment of VDAC1 in LUAD. A549 cells with VDAC1 knockdown and H1650 cells with VDAC1 overexpression were established through lentiviral transfection. The expression difference of VDAC1 protein in LUAD and adjacent tissue specimens was detected by immunohistochemistry.The effects of VDAC1 on the proliferation, migration, and invasion capabilities were explored through CCK8 assay, scratch healing assay, and Transwell assay.The activation levels of epithelial-mesenchymal transition (EMT) marker proteins, cell cycle-dependent kinases, and molecules in the PI3K/AKT/mTOR signaling pathway were detected by Western blot.Results:Bioinformatics analysis revealed that VDAC1 was highly expressed in LUAD cells ( P<0.000 1) and was an independent risk factor for LUAD ( P<0.000 1). Functional enrichment analysis showed significant enrichment of the PI3K/AKT/mTOR, G2M checkpoint, and P53 signaling pathways ( P<0.001). Compared to adjacent control tissues, the expression level of VDAC1 protein is higher in lung adenocarcinoma tissues.Overexpression of VDAC1 promoted the proliferation ( P<0.000 1), migration, and invasion( P<0.01) of H1650 cells, while knockdown of VDAC1 inhibited the proliferation ( P<0.000 1), migration, and invasion ( P<0.05) of A549 cells.Western Blot experiments showed that compared to the control group, the expression levels of vimentin (1.10±0.11 vs 2.39±0.15, P<0.001), N-cadherin (0.94±0.12 vs 2.72±0.06, P<0.001), CDK1 (0.93±0.04 vs 1.53±0.03, P<0.000 1), CDK2 (1.04±0.13 vs 2.29±0.06, P<0.001), CDK4 (0.90±0.03 vs 2.00±0.11, P<0.01), p-PI3K (1.08±0.13 vs 1.85±0.12, P<0.01), and p-AKT (1.03±0.11 vs 1.69±0.06, P<0.001) were increased in H1650 cells overexpressing VDAC1, while E-cadherin expression decreased (2.18±0.14 vs 0.997±0.11, P<0.001).In contrast, in A549 cells with VDAC1 knockdown, the expression levels of vimentin (1.70±0.26 vs 0.97±0.09, P<0.05), N-cadherin (1.98±0.25 vs 1.03±0.06, P<0.05), CDK1 (1.13±0.03 vs 0.95±0.02, P<0.01), CDK2 (2.29±0.12 vs 0.92±0.10, P<0.001), CDK4 (1.71±0.096 vs 1.12±0.11, P<0.01), p-PI3K (1.67±0.09 vs 0.97±0.03, P<0.001), and p-AKT (1.53±0.04 vs 1.02±0.03, P<0.000 1) decreased, while E-cadherin expression increased (1.04±0.04 vs 1.85±0.26, P<0.05). Conclusions:VDAC1 may promote the proliferation, migration, and invasion of LUAD cells by activating EMT and cyclin-dependent kinases through the PI3K/AKT/mTOR pathway.
7.Application of Taylor spatial frame for treating post-burn foot and ankle deformities in adults.
Jianming GU ; Shihao WANG ; Hui DU ; Yixin ZHOU
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(8):974-981
OBJECTIVE:
To investigate the safety and effectiveness of using the Taylor spatial frame (TSF) based on the Ilizarov tension-stress principle for treatment of post-burn foot and ankle deformities in adults.
METHODS:
A clinical data of 6 patients with post-burn foot and ankle deformities treated between April 2019 and November 2023 was retrospectively analyzed. There was 1 male and 5 females with an average age of 28.7 years (range, 20-49 years). There were 3 cases of simple ankle equinus, 2 cases of ankle equinus, midfoot rocker-bottom foot, and forefoot pronation, and 1 case of calcaneus foot and forefoot pronation. Preoperative American Orthopedic Foot and Ankle Society (AOFAS) score was 45.3±18.2, 12-Item Short-Form Health Survey (SF-12)-Physical Component Summary (PCS) score was 34.3±7.3 and Mental Component Summary (MCS) score was 50.4±8.8. Imaging examination showed tibial-calcaneal angle of (79.8±31.5)°, calcaneus-first metatarsal angle of (154.5±45.3)°, talus-first metatarsal angle of (-19.3±35.0)°. Except for 1 case with severe deformity that could not be measured, the remaining 5 cases had talus-second metatarsal angle of (40.6±16.4)°. The deformities were fixed with TSF after soft tissue release and osteotomy. Then, the residual deformities were gradually corrected according to software-calculated prescriptions. TSF was removed after maximum deformity correction and osteotomy healing. External fixation time, brace wearing time after removing the TSF, and pin tract infection occurrence were recorded. Infection severity was evaluated based on Checketts-Otterburns grading. Joint function was evaluated using AOFAS score and SF-12 PCS and MCS scores. Patient satisfaction was assessed using Likert score. Imaging follow-up measured relevant indicators to evaluate the degree of deformity correction. Deformity recurrence was observed during follow-up.
RESULTS:
The external fixation time was 103-268 days (mean, 193.5 days). The mild pin tract infections occurred during external fixation in all patients, which healed after pin tract care and oral antibiotics. No serious complication such as osteomyelitis, fractures, neurovascular injury, or skin necrosis occurred. After external fixation removal, 3 cases did not wear braces, while the remaining 3 cases wore braces continuously for 6 weeks, 8 weeks, and 3 years, respectively. All patients were followed up 13.9-70.0 months, with an average of 41.7 months. During follow-up, none of the 6 patients had recurrence of foot deformity. At 1 year after operation, the AOFAS score was 70.0±18.1, SF-12-PCS and MCS scores were 48.9±4.5 and 58.8±6.4, respectively, all showing significant improvement compared to preoperative values ( P<0.05). Imaging follow-up showed that all osteotomies healed, and all distraction cases achieved bony union at 6 months after stopping stretching. At 1 year after operation, tibial-calcaneal angle was (117.5±12.8)° and talus-first metatarsal angle was (-3.3±19.3)°, both showing significant improvement compared to preoperative values ( P<0.05). Calcaneus-first metatarsal angle was (132.0±14.4)°, which also improved compared to preoperative values but without significant difference ( P>0.05). Except for 1 case with severe deformity that could not be measured, the remaining 5 cases had talus-second metatarsal angle of (18.0±6.4)°. And there was no significant difference ( P>0.05) between pre-and post-operative data of 4 patients with complete data. At 1 year after operation, 1 patient was satisfied with effectiveness and 5 patients were very satisfied.
CONCLUSION
The TSF, by applying the Ilizarov tension-stress principle for gradual distraction and multi-planar adjustment, combined with soft tissue release and osteotomy, can effectively correct foot and ankle deformities after burns, especially equinus deformity with contracture of the posterior soft tissues of the lower leg. There are still limitations in treating cases with tight, adherent scars on the dorsum of the foot that require long-distance distraction. If necessary, a multidisciplinary approach combined with microsurgical techniques can be utilized.
Humans
;
Adult
;
Male
;
Female
;
Middle Aged
;
Retrospective Studies
;
External Fixators
;
Young Adult
;
Burns/complications*
;
Foot Deformities, Acquired/etiology*
;
Treatment Outcome
;
Ilizarov Technique/instrumentation*
8.Biological characteristics of spontaneous ovarian cancer in Microtusfortis.
Junkang ZHOU ; Tianqiong HE ; Yixin WEN ; Qian LIU ; Wenling ZHI ; Lingxuan OUYANG ; Yushan QI ; Xin GAO ; Zikang ZHOU ; Zhijun ZHOU
Journal of Central South University(Medical Sciences) 2025;50(1):11-22
OBJECTIVES:
Wild-caught Microtus fortis (M. fortis) at the age of 9-15 months can develop epithelial ovarian cancers similar to human epithelial ovarian cancers under natural conditions during experimental animal breeding, but its pathological types and biological characteristics remain unclear. This study aims to analyze the biological characteristics of spontaneous ovarian cancer in M. fortis, intending to develop M. fortis as an animal model for human epithelial ovarian cancer.
METHODS:
The female M. fortis (9-15 months old) with spontaneous ovarian cancer were selected as the experimental group, and healthy M. fortis from the same litter were selected as the control group. The ovarian pathological changes of the two groups were observed by dissection. Blood routine and biochemical indicators were measured by biochemical analysis. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the ovarian cancer tissue of M. fortis. Immunohistochemical staining was used to detect the protein expression of common ovarian cancer markers, and real-time RT-PCR was used to analyze the transcription levels of ovarian cancer-related genes.
RESULTS:
Spontaneous ovarian cancer in M. fortis mainly affects both ovaries, with tumors appearing solid or cystic. HE staining and histopathological analysis confirmed that the ovarian tumors originated from ovarian surface epithelium. Compared to the control group, the experimental group showed significantly decreased hemoglobin (P<0.01), hematocrit (P<0.05), albumin (P<0.05), and blood glucose levels (P<0.01), while lymphocyte percentage (P<0.05), monocyte percentage (P<0.05), cholesterol (P<0.01), and progesterone (P<0.01) levels were significantly increased. Expression of ovarian cancer-related genes, including ID3, CDC42, RHOA, RB1CC1, NF1, PIN1, MIB1, PDS5A, MCM7, and MLH1, was significantly downregulated (all P<0.05), while PAX8 gene expression was significantly upregulated (P<0.05). Immunohistochemical results showed that Wilms' tumor gene 1 (WT1) protein was mainly distributed throughout the cell, with significantly higher expression in ovarian cancer M. fortis. Tumor protein 53 (TP53) was expressed in both healthy and ovarian cancer M. fortis and was distributed throughout the cell. Hepatocyte nuclear factor 1 beta (HNF1B) and progesterone receptor (PR) protein were highly expressed in the ovarian tissue of healthy M. fortis but were significantly reduced in the ovarian cancer M. fortis, though both were located in the cytoplasm.
CONCLUSIONS
Spontaneous ovarian cancer in M. fortis is serous ovarian cancer. Compared to healthy M. fortis, significant differences were observed in ovarian tissue morphology, biochemical indicators, ovarian cancer-related gene expression, and protein expression, which show similarity to the biological characteristics of human serous ovarian cancer. This suggests that M. fortis could be an ideal animal model for studying human serous ovarian cancer.
Female
;
Ovarian Neoplasms/metabolism*
;
Animals
;
Carcinoma, Ovarian Epithelial
;
Disease Models, Animal
;
Humans
;
Neoplasms, Glandular and Epithelial/metabolism*
;
Ovary/pathology*
9.Mechanism by which Tongan Decoction regulates synovial macrophage polarization in rats with knee osteoarthritis
Yixin CHEN ; Yan LU ; Xuan ZHANG ; Xiaoli CHEN ; Liangyuan TAN ; Zhangjie XU ; Wanglong CHEN ; Shaoting SU ; Jiyao LIANG ; Honghai ZHOU
Chinese Journal of Tissue Engineering Research 2025;29(26):5621-5631
BACKGROUND:Developed by the esteemed Chinese medicine master Wei Guikang,Tongan Decoction has proven highly effective in treating knee osteoarthritis.However,the mechanism of action is yet unclear.OBJECTIVE:To elucidate how Tongan Decoction modulates synovial macrophage polarization as a therapeutic strategy for knee osteoarthritis in a rat model.METHODS:(1)We employed high-throughput microRNA sequencing and polymerase chain reaction to analyze the differentially expressed miRNA in synovial macrophages of normal and knee osteoarthritis rats.Predicted target genes of miR-27a were identified using bioinformatics databases,with subsequent validation through luciferase assays.A total of 68 Sprague-Dawley rats were randomly divided into normal control group(n=16),model group(n=16),miR-27a overexpression group(n=12),Tongan Decoction group(n=12),and Tongan Decoction+miR-27a inhibition group(n=12).The miR-27a overexpression group and the Tongan Decoction+miR-27a inhibition group were injected with miR-27a mimic and miR-27a inhibitor in the right knee joint cavity,respectively,once daily for 5 continuous days.On the 15th day after modeling,the Tongan Decoction group and the Tongan Decoction+miR-27a inhibition group were given Tongan Decoction by gastric lavage,and the other three groups were given saline by gastric lavage,once daily for 14 continuous days.After administration,behavioral tests,X-rays,hematoxylin-eosin staining of synovial and cartilage tissues of the knee joint and immunofluorescence staining of synovial tissues of the knee joint,RT-PCR,and Western blot were performed.RESULTS AND CONCLUSION:High-throughput sequencing of miRNA showed low expression of miR-27a in synovial tissues of rats with knee osteoarthritis.The target gene of miR-27a was nuclear factor κB,and luciferase assay showed that the two could bind to each other.Behavioral assays showed that miR-27a overexpression or Tongan Decoction alleviated joint dysfunction in rats with knee osteoarthritis,and miR-27a inhibition antagonized the effect of Tongan Decoction.X-ray films and hematoxylin-eosin staining showed that miR-27a overexpression or Tongan Decoction reduced the degree of knee osteoarthritis and miR-27a inhibition weakened the therapeutic effect of Tongan Decoction.The results of RT-PCR and western blot assay showed that compared with the normal control group,the expression of interleukin 10 was reduced in the model group(P<0.05),and the expression of matrix metalloproteinase 13,interleukin 1β,and nuclear factor κB was elevated in the model group(P<0.05).miR-27a overexpression or Tongan Decoction could differently reverse the changes in the above-mentioned indexes,while miR-27a inhibition weakened the effect of Tongan Decoction.Immunofluorescence staining results showed that CD86 protein expression in the model group was higher than that in the normal control group(P<0.05),and CD206 protein expression was lower than that in the normal control group(P<0.05);miR-27a overexpression group and Tongan Decoction had lower CD86 protein expression than that in the model group(P<0.05),and higher CD206 protein expression than that in the model group(P<0.05);in the Tongan Decoction+miR-27a inhibition group,CD86 protein expression was higher(P<0.05)and CD206 protein expression was lower than that in the Tongan Decoction group(P<0.05).Tongan Decoction mitigates knee osteoarthritis by upregulating miR-27a expression and suppressing nuclear factor κB activity,which improves knee joint function and further treats knee osteoarthritis.
10.Dihydroartemisinin enhances doxorubicin-induced apoptosis of triple negative breast cancer cells by negatively regulating the STAT3/HIF-1α pathway.
Di CHEN ; Ying LÜ ; Yixin GUO ; Yirong ZHANG ; Ruixuan WANG ; Xiaoruo ZHOU ; Yuxin CHEN ; Xiaohui WU
Journal of Southern Medical University 2025;45(2):254-260
OBJECTIVES:
To investigate the effects of dihydroartemisinin (DHA) combined with doxorubicin (DOX) on proliferation and apoptosis of triple-negative breast cancer cells and explore the underlying molecular mechanism.
METHODS:
MDA-MB-231 cells were treated with 50, 100 or 150 μmol/L DHA, 0.5 μmol/L DOX, or with 50 μmol/L DHA combined with 0.5 μmol/L DOX. The changes in proliferation and survival of the treated cells were examined with MTT assay and colony-forming assay, and cell apoptosis was analyzed with flow cytometry. Western blotting was performed to detect the changes in protein expression levels of PCNA, cleaved PARP, Bcl-2, Bax, STAT3, p-STAT3, HIF-1α and survivin.
RESULTS:
The IC50 of DHA was 131.37±29.87 μmol/L in MDA-MB-231 cells. The cells with the combined treatment with DHA and DOX showed significant suppression of cell proliferation. Treatment with DHA alone induced apoptosis of MDA-MB-231 cells in a dose-dependent manner, but the combined treatment produced a much stronger apoptosis-inducing effect than both DHA and DOX alone. DHA at 150 μmol/L significantly inhibited clone formation of MDA-MB-231 cells, markedly reduced cellular expression levels of PCNA, p-STAT3, HIF-1α and survivin proteins, and obviously increased the expression level of cleaved PARP protein and the Bax/Bcl-2 ratio, and the combined treatment further reduced the expression level of p-STAT3 protein and increased the Bax/Bcl-2 ratio.
CONCLUSIONS
DHA combined with DOX produces significantly enhanced effects for inhibiting cell proliferation and inducing apoptosis in MDA-MB-231 cells possibly as result of DHA-mediated negative regulation of the STAT3/HIF-1α pathway.
Humans
;
STAT3 Transcription Factor/metabolism*
;
Apoptosis/drug effects*
;
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
;
Doxorubicin/pharmacology*
;
Triple Negative Breast Neoplasms/metabolism*
;
Cell Line, Tumor
;
Artemisinins/pharmacology*
;
Female
;
Cell Proliferation/drug effects*
;
Signal Transduction/drug effects*
;
Survivin

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