1.Effect of Xibining Formula (膝痹宁) on Knee Cartilage Tissue Damage and the cGAS-STING Signaling Pathway in Knee Osteoarthritis Model Mice
Houyu FU ; Xiaochen LI ; Zijian GONG ; Lishi JIE ; Jiangyu LIU ; Yingqi CHEN ; Peimin WANG
Journal of Traditional Chinese Medicine 2025;66(12):1257-1264
ObjectiveTo investigate the possible mechanism of action of Xibining Formula (膝痹宁) for cartilage damage in knee osteoarthritis (KOA) through the cyclic guanosine-adenosine monophosphate synthase (cGAS)- stimulator of interferon genes (STING) signaling pathway. MethodsFifty C57BL/6J mice were randomly divided into five groups (10 per group), sham operation group, KOA model group, low-dose Xibining Formula group, high-dose Xibining Formula group, and high-dose Xibining Formula + agonist group. The KOA models were constructed using the destabilization of the medial meniscus (DMM) method in all groups but the sham surgery group. Two weeks after surgery, the low- and high-dose Xibining Formula groups were administered Xibining Formula at doses of 3.58 g/(kg·d) and 14.32 g/(kg·d) respectively via gavage. The high-dose Xibining Formula + agonist group received 14.32 g/(kg·d) of Xibining Formula via gavage followed by an intraperitoneal injection of Vadimezan (DMXAA) at 25 mg/kg. The sham surgery group and the KOA model group mice were given an equivalent volume of normal saline at 5 ml/(kg·d) via gavage, once daily for four consecutive weeks. Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were measured by ELISA; pathological changes in cartilage tissue were observed using hematoxylin-eosin (HE) staining and Safranin O-Fast Green staining. Pathological changes were scored according to the Mankin scoring system; the levels of cartilage tissue matrix regulation-related indicators such as matrix metalloproteinase 3 (MMP3), matrix metalloproteinase 13 (MMP13), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS), type-Ⅱ collagen (CⅡ) and aggregated proteoglycan (Aggrecan), and also cGAS-STING pathway-related protein and mRNA expression levels were detected by Western blot and qPCR methods. ResultsCompared with the sham surgery group, the KOA model group showed severe cartilage edge destruction, significantly increased Mankin scores, significantly decreased protein and mRNA expression levels of COLⅡ and Aggrecan, and significantly increased protein and mRNA expression levels of cGAS, STING, MMP3, MMP13, and ADAMTS5 (P<0.01). Compared with the control group, serum level of IL-6, IL-1β, TNF-α in all the intervented groups decreased (P<0.01), while compared with high-dose Xibining Formula group, level of IL-6, IL-1β, and TNF-α in low-dose Xibining Formula group and high-dose Xibining Formula + agonist group increased (P<0.01). Compared with the KOA model group, all the intervention groups exhibited alleviated cartilage pathological changes, signi-ficantly reduced Mankin scores, significantly increased protein and mRNA expression levels of COLⅡ and Aggrecan, and significantly decreased protein and mRNA expression levels of cGAS, STING, MMP3, MMP13, and ADAMTS5 (P<0.01). Compared with high-dose Xibining Formula group, high-dose Xibining Formula + agonist group showed cartilage edge destruction, significantly increased Mankin scores, significantly decreased protein and mRNA expression levels of COLⅡ and Aggrecan, and increased protein and mRNA expression levels of cGAS, STING, MMP3, MMP13, and ADAMTS5 (P<0.01). ConclusionXibining Formula may improve KOA cartilage damage by inhibiting the cGAS-STING signaling pathway, decreasing matrix degradation-related proteins, and elevating matrix composition-related proteins.
2.Endovascular therapy for early neurological deterioration in patients with minor stroke due to anterior circulation large vessel occlusion: comparison with medical treatment
Zhonglun CHEN ; Zhaokun LI ; Mingjun PU ; Shanshan ZHANG ; Xianwen ZHANG ; Xiaochen GONG ; Yufeng TANG
International Journal of Cerebrovascular Diseases 2025;33(7):508-514
Objective:To investigate the efficacy and safety of endovascular therapy (EVT) for early neurological deterioration (END) in patients with minor stroke due to acute anterior circulation large vessel occlusion.Methods:Consecutive patients with mild stroke due to acute anterior circulation large vessel occlusion admitted to Mianyang Central Hospital from October 2015 to October 2023 were included retrospectively. Minor stroke was defined as a baseline National Institutes of Health Stroke Scale (NIHSS) score <6. END was defined as an increase of ≥4 in NIHSS score compared to baseline within 12 hours of onset. According to whether EVT was performed or not, they were divided into EVT group and standard medical treatment (SMT) group. At 90 days after onset, the modified Rankin Scale was used to evaluate the outcome. 0-1 was defined as excellent outcome (primary outcome measure) and 0-2 was defined as good outcome (secondary outcome measure). The safety endpoints included symptomatic intracranial hemorrhage (sICH) within 72 hours after EVT and all-cause mortality within 90 days. Multivariate logistic regression analysis was used to determine the correlation between EVT and clinical outcome. Results:A total of 164 patients with minor stroke due to acute anterior circulation large vessel occlusion were included. Eighty-four patients (51.2%) developed END, of which 52 (61.9%) underwent EVT and 32 (38.1%) received SMT; 60 patients (71.4%) had excellent outcome, and 64 (76.2%) had good outcome. There was no significant difference in demographic and baseline clinical data between the EVT group and the SMT group. The excellent outcome rate of the EVT group at 90 days after onset showed a trend higher than that of SMT group (78.8% vs. 59.4%; χ2=3.680, P=0.055), but there was no significant difference in the good outcome rate and safety endpoints between the two groups. Multivariate logistic regression analysis showed that after adjusting for confounding factors, EVT was significantly and independently associated with excellent outcome at 90 days (odds ratio 4.955, 95% confidence interval 1.331-22.284; P=0.024). Conclusion:For patients with minor stroke due to anterior circulation large vessel occlusion who experience END, EVT may improve their functional outcome without increasing the risk of sICH and mortality.
3.Early Plasma Circulating Tumor DNA as a Potential Biomarker of Disease Recurrence in Non-metastatic Prostate Cancer
Xiaochen FEI ; Xinxing DU ; Yiming GONG ; Jiazhou LIU ; Liancheng FAN ; Jiayi WANG ; Yanqing WANG ; Yinjie ZHU ; Jiahua PAN ; Baijun DONG ; Wei XUE
Cancer Research and Treatment 2023;55(3):969-977
Purpose:
In non-metastatic prostate cancer (nmPCa) setting, it is important to early identify the patients at risk of biochemical recurrence (BCR) for immediate postoperative intervention. Our study aimed to evaluate the potential clinical utility of circulating tumor DNA (ctDNA) for predicting disease recurrence.
Materials and Methods:
This real-world observational study evaluated 161 cases of nmPCa undergoing next-generation sequencing at our institution. A total of 139 ctDNA samples and 31 biopsied tumor tissue underwent genomic profiling. The study endpoint was BCR after radical prostatectomy. Relationships between the ctDNA status and the biochemical progression-free survival (bPFS) were analyzed by log-rank test and multivariate Cox regression.
Results:
Of 161 enrolled patients, 19 (11.8%) harbored deleterious alterations in NCOR2, followed by BRCA2 (3.7%), ATR (2.5%), and CDK12 (2.5%). Of available pre-operative blood samples (n=139), ctDNA was detectable in 91 (65.5%). Until last follow-up, 56 of 68 patients (85.3%) with detectable ctDNA had achieved BCR, whereas only eight of 39 patients (20.5%) with undetectable ctDNA had achieved BCR. Patients who had undetectable ctDNA experienced significantly longer bPFS compared with those who had detectable ctDNA (not available vs. 8.2 months; hazard ratio, 0.14; p < 0.01). Pre-operative ctDNA status was a significant prognostic factor of disease recurrence.
Conclusion
Pre-operative ctDNA detection could identify patients at high risk of recurrence and has the potential to inform immediate postoperative interventions, but these approaches remain to be validated in prospective studies. ctDNA studies can provide insights into accurate monitoring and precise treatment rather than simply following routine clinical care.
4.Effects of Age and Gender on Lumbar Proprioception
Xiaochen LIU ; Fang CUI ; Yulin DONG ; Yili ZHENG ; Haoyu HU ; Di GONG ; Juan ZHANG ; Changcheng CHEN ; Ge SONG ; Xueqiang WANG
Chinese Journal of Rehabilitation Theory and Practice 2018;24(12):1446-1450
Objective To explore the difference in lumbar proprioception between the youth and the elderly, and the male and the female. Methods From September to November, 2017, 58 elderly aged 65 to 80 years and 56 youth aged 20 to 30 years were randomly picked up from the community. Their lumbar proprioceptions were measured by Con-Trex isokinetic dynamometer. The absolute error angles of lumbar flexion and extension in passive replication test was used to assess lumbar proprioceptive function. Results The absolute error angles of passive replication test were less on youth proprioception than on elderly ones (t > 4.218, P < 0.001), either in men or women (t > 2.844, P < 0.001), and was not different between men and women neither in the elderly group nor in the youth group (t < 1.473, P > 0.05). Conclusion The lumbar proprioception in the elderly was obviously inferior to that of the youth, both men and women. There was no gender difference between men and women in lumbar proprioception, both elderly and youth.
5. Treatment of patients with different degree of acute respiratory distress syndrome caused by inhalation of white smoke
Fuwang YANG ; Haiming XIN ; Jinhong ZHU ; Xiaoyan FENG ; Xiaochen JIANG ; Zhenyu GONG ; Yalin TONG
Chinese Journal of Burns 2017;33(12):760-765
Objective:
To summarize the treatment experience of patients with different degree of acute respiratory distress syndrome (ARDS) caused by inhalation of white smoke from burning smoke bomb.
Methods:
A batch of 13 patients with different degree of ARDS caused by inhalation of white smoke from burning smoke bomb, including 2 patients complicated by pulmonary fibrosis at the late stage, were admitted to our unit in February 2016. Patients were divided into mild (9 cases), moderate (2 cases), and serious (2 cases) degree according to the ARDS Berlin diagnostic criteria. Patients with mild and moderate ARDS were conventionally treated with glucocorticoid. Patients with severe ARDS were sequentially treated with glucocorticoid and pirfenidone, and ventilator-assisted breathing, etc. were applied. The vital signs, arterial oxygenation index, changes of lung imaging, pulmonary ventilation function, general condition, and the other important organs/systems function were timely monitored according to the condition of patients. The above indexes were also monitored during the follow-up time of 10-15 months post injury. Data were processed with SPSS 18.0 statistical software.
Results:
(1) The symptoms of respiratory system of patients with mild and moderate ARDS almost disappeared after 3 days′ treatment. Their arterial oxygenation index was decreased from post injury day 1 to 4, which almost recovered on post injury day 7 and completely recovered one month post injury. The symptoms of respiratory system of patients with severe ARDS almost disappeared at tranquillization condition 1-3 month (s) post injury. Their arterial oxygenation index was decreased from post injury day 3 to 21, which gradually recovered 1-3 month (s) post injury and was normal 15 months post injury. (2) Within 24 hours post injury, there was no obvious abnormality or only a little texture enlargement of lung in image of chest CT or X-rays of patients with mild and moderate ARDS. One patient with moderate ARDS had diffuse patchy and ground-glass like increased density shadow (pulmonary exudation for short) at post injury hour 96. Chest iconography of all patients with mild and moderate ARDS showed no abnormalities 10 months post injury. Both lungs of each of the two patients with severe ARDS showed obvious pulmonary exudation at post injury hours 45 and 75, respectively. One patient with severe ARDS showed no abnormality in chest image 10 months post injury, but there was still a small mesh-like increased density shadow in double lobes with slight adhesion of pleura in the other patient with severe ARDS 15 months post injury. (3) All patients showed severe restrictive hypoventilation when admitted to hospital. Pulmonary ventilation function of patients with mild and moderate ARDS recovered to normal one month post injury, and they could do exercises like running, etc. Pulmonary ventilation function of one patient with severe ARDS recovered to normal 6 months post injury, and the patient could do exercises like running, etc. The other patient with severe ARDS showed mild restrictive hypoventilation 15 months post injury and could do exercises like rapid walking, etc. (4) The condition of all mild and one moderate ARDS patients was better on post injury day 3, and they were transferred to the local hospital for subsequent treatment and left hospital on post injury day 21. One patient with moderate ARDS healed and left hospital on post injury day 29. Patients with severe ARDS healed and left hospital on post injury day 81. During the follow-up time of 10-15 months post injury, the other important organs/systems of all patients showed no abnormality, and there was no adverse reaction of glucocorticoid like osteoporosis, femoral head necrosis, or metabolic disorder. Two patients with severe ARDS did not have any adverse reaction of pirfenidone like liver function damage, photosensitivity, anorexia, or lethargy.
Conclusions
Early enough and uninterrupted application of glucocorticoid can significantly reduce the ARDS of patients caused by inhalation of white smoke from burning smoke bomb. Sequential application of glucocorticoid and pirfenidone can effectively treat pulmonary fibrosis at the late stage.
6.Relationship Between Thyroid Hormone and Atrial Fibrillation Prevalence in Patients With Chronic Heart Failure
Chen LIU ; Xiaochen YUAN ; Zhengang ZHANG ; Qiuping LUO ; Junfeng YAN ; Kaizheng GONG ; Jianhua QIN ; Guijian ZHOU
Chinese Circulation Journal 2015;(8):749-752
Objective: To investigate the impact of thyroid hormone on atrial ifbrillation (AF) prevalence in patients with chronic heart failure (CHF).
Methods: A total of 322 non-valvular heart disease CHF patients treated in our hospital from 2011-0-01 to 2012-10-01 were retrospectively studied. Based on previous history and the ECG at admission, the patients were divided into 2 groups: AF group,n=187 and Sinus rhythm group,n=135. The proifle of serum levels of free thyroxine (FT4), free triiodothyronine (FT3), hyroid stimulating hormone (TSH) and LDL-C were examined within 24 hours of admission; 12 lead ECG and echocardiography were conducted to analyze the related factor for AF occurrence.
Results: Compared with Sinus rhythm group, AF group had increased FT4 level as 14.52 (12.74, 15.85) pmol/L vs 13.11 (11.68, 14.85) pmol/L,P<0.001, while FT3 level was similar between 2 groups as 4.06 (3.76, 4.44) pmol/L vs 4.1(3.80, 4.52) pmol/L,P=0.250. Spearman related analysis indicated that FT4 level was positively related to left atrial dimension (LAD) (r=0.134,P=0.016), FT3 level was positively related to LDL-C (r=0.235,P<0.001) and negatively related to age (r=-0.268, P<0.001). Taking FT4 as the continuous variable, Logistic regression analysis indicated that FT4 level [OR=1.227, 95% CI (1.112-1.354),P<0.001], LAD [OR=1.154, 95% CI (1.105-1.205),P<0.001], age [OR=1.038, 95% CI (1.012-1.064),P=0.003], CHF duration [OR=1.111, 95% CI (1.021-1.209),P=0.015], LDL-C level [OR=0.689, 95% CI (0.493-0.963),P=0.029] were related to AF prevalence in CHF patients.
Conclusion: High serum level of FT4 may increase the risk AF occurrence in CHF patients.

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