Objective To establish an acute rejection model of cervical heart transplantation in mice and evaluate the survival and dynamic rejection process post-transplantation. Methods Mice were randomly divided into sham operation group (n=10), syngeneic transplantation group (n=21), and allogeneic transplantation group (n=65). Sham operation, syngeneic cervical heart transplantation, and allogeneic cervical heart transplantation were performed respectively. The survival of recipient mice and grafts, histopathological changes of graft tissues, subpopulations of splenic lymphocytes, and expression of inflammatory factors in serum and grafts were observed. Results The survival rate and graft survival rate of the sham operation group and syngeneic transplantation group were 100% at 7 days after surgery. In the allogeneic transplantation group, 5 cases failed and died on the first day after surgery. The survival rate at 7 days after surgery was 86%, and all surviving mice had grafts that stopped beating at 7 days after surgery. The allogeneic transplantation group showed significant rejection at 7 days after surgery, accompanied by tissue damage and CD8⁺ T cell infiltration. The proportion of CD8⁺ T cells in the spleen continued to rise post-operation, while the proportion of CD4⁺ T cells showed a downward trend. The expression of interferon-γ in serum and grafts peaked at 5 days after surgery, while the expression of tumor necrosis factor-α showed no statistical significance. Conclusions Acute rejection following heart transplantation in mice intensifies between 5 to 7 days after surgery, which may be a critical time window for immunological intervention.

This article aimed to summarise the clinical experience of Professor XIONG Jibai in treating henoch-schonlein purpura （HSP） from the perspective of "simultaneous treatment of wind and blood". HSP was devided into acute phase and transitional phase in clinic. It was considered that the wind pathogen exists throughout the disease course， and the treatment is guided by the "four methods of treating blood" in TANG Rongchuan's Treatise on Blood Syndromes - Blood Vomiting （《血证论·吐血》）， which are stanching bleeding， expelling stasis， tranquilising blood， and tonifying blood. In the acute phase， wind-heat damaging collateral symdrome and blood-heat frenetic flow syndrome are common， which could be treated by the method of cooling blood to dispel wind， and eliminating stasis to stop bleeding， with self-prescribed modified Ziping Xiaofeng Powder （紫萍消风散）； in the transitional phase， syndrome of effulgent fire due to yin deficiency and syndrome of qi deficiency failing to control are common， which could be treated by the method of tranquilising blood and tonifying deficiency， with modified Zhibai Dihuang Decoction （知柏地黄汤） and Guipi Decoction （归脾汤）. At the same time， it is believed that wind-related medicinal has the function of eliminating stasis， stanching bleeding， and cooling blood， and the wind-related medicinal should be used throughout the treatment.

Objective To investigate the application value of CT perfusion imaging in patient with traumatic brain injury(TBI).Methods Thirty-seven patients with TBI were included retrospectively and divided into mild,moderate,and severe groups according to Glasgow coma scale(GCS)score.Perfusion parameters of the cerebral hemispheres on the injured side and the contralateral side of the level of basal ganglia were compared.After three months,the correlations between perfusion parameters and GCS score at baseline and Glasgow outcome scale-extended(GOSE)score at follow-up were further analyzed,respectively.Results The injured side of TBI patients showed hypo-perfusion compared with that of the contralateral side.The abnormal perfusion volumes of time to maximum of the residual function(Tmax)>10 s was significantly negatively correlated with GOSE score(ρ=-0.55,P=0.01),and could distinguish the good prognosis group from the poor prognosis group with GOSE score[area under the curve(AUC)=0.82,P= 0.01].In the group of patients undergoing decompressive craniectomy,the abnormal perfusion volumes of Tmax>4 s and Tmax>6 s were significantly associated with GCS score(ρ=0.61,P=0.01;ρ=0.53,P=0.03).Conclusion CT perfusion imaging may be useful in assessing the hemodynamics and severity of TBI,and in predicting the clinical prognosis.

Long noncoding RNAs (lncRNAs) play a critical role in the regulation of atherosclerosis. Here, we investigated the role of the lncRNA growth arrest-specific 5 (lncR-GAS5) in atherogenesis. We found that the enforced expression of lncR-GAS5 contributed to the development of atherosclerosis, which presented as increased plaque size and reduced collagen content. Moreover, impaired autophagy was observed, as shown by a decreased LC3II/LC3I protein ratio and an elevated P62 level in lncR-GAS5-overexpressing human aortic endothelial cells. By contrast, lncR-GAS5 knockdown promoted autophagy. Moreover, serine/arginine-rich splicing factor 10 (SRSF10) knockdown increased the LC3II/LC3I ratio and decreased the P62 level, thus enhancing the formation of autophagic vacuoles, autolysosomes, and autophagosomes. Mechanistically, lncR-GAS5 regulated the downstream splicing factor SRSF10 to impair autophagy in the endothelium, which was reversed by the knockdown of SRSF10. Further results revealed that overexpression of the lncR-GAS5-targeted gene miR-193-5p promoted autophagy and autophagic vacuole accumulation by repressing its direct target gene, SRSF10. Notably, miR-193-5p overexpression decreased plaque size and increased collagen content. Altogether, these findings demonstrate that lncR-GAS5 partially contributes to atherogenesis and plaque instability by impairing endothelial autophagy. In conclusion, lncR-GAS5 overexpression arrested endothelial autophagy through the miR-193-5p/SRSF10 signaling pathway. Thus, miR-193-5p/SRSF10 may serve as a novel treatment target for atherosclerosis.
Humans ; Atherosclerosis/genetics* ; Autophagy/genetics* ; Cell Cycle Proteins/metabolism* ; Endothelial Cells/metabolism* ; Endothelium/metabolism* ; MicroRNAs/metabolism* ; Repressor Proteins/metabolism* ; RNA Splicing Factors ; Serine-Arginine Splicing Factors/genetics* ; RNA, Long Noncoding/metabolism*

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective To investigate the effect of atractylenolide Ⅲ(A Ⅲ)on stroke in spon-taneously hypertensive rats by regulating microRNA-296-5p(miR-296-5p)expression.Methods The spontaneously hypertensive rats(SHR)were given 0.9％sodium chloride solution freely for 2 months,and then fed with 1％sodium chloride solution to establish the stroke model of SHR.The rat models were randomly grouped into Model group,A Ⅲ low-dose group(A Ⅲ-L group),A Ⅲ high-dose group(A Ⅲ-H group),positive drug nimodipine group(Nim group),miR-296-5p agonist group(miR-296-5p agomir group),agomir NC group,A Ⅲ-H+miR-296-5p agomir group,and A Ⅲ-H+agomir NC group,with 12 in each group.The changes in neurological symptom scores,av-erage arterial pressure,survival time,and platelet adhesion rate were detected and recorded;hema-toxylin and eosin(HE)staining was applied to detect pathological changes in the CA1 region of the rat hippocampus;quantitative reverse transcription polymerase chain reaction(qRT-PCR)was ap-plied to detect the expression of miR-296-5p in the hippocampal CA1 region.Results Compared with the NC group,the Model group showed increases in neurological symptom score,mean arterial pressure,platelet adhesion rate,miR-296-5p expression,shortened survival time,and severe pathological damage to the hippocampal CA1 area(P＜0.05);compared with the Model group,the neurological symptom scores,mean arterial pressure,platelet adhesion rate,and miR-296-5p expression in the A Ⅲ-L,A Ⅲ-H,and Nim groups decreased,the survival time was prolonged,and the pathological damage in the CA1 area of the hippocampus was alleviated(P＜0.05);compared with Model group and agomir NC group,neurological symptom score,mean arterial pressure,platelet adhesion rate and miR-296-5p expression of rats in the miR-296-5p agomir group were increased,survival time was shortened,and pathological damage in hippocampal CA1 region was aggravated(P＜0.05).compared with the A Ⅲ-H group and the AⅢ-H+agomir NC group,the neurological symptom score,average arterial pressure,platelet adhesion rate and miR-296-5p expression of rats were in-creased,the survival time was shortened,and the pathological damage in hippocampal CA1 region was serious in the AⅢ-H+miR-296-5p agomir group(P＜0.05).Conclusion A Ⅲ may treat SHR stroke by inhibiting the expression of miR-296-5p.

Objective To investigate the effect of atractylenolide Ⅲ(A Ⅲ)on stroke in spon-taneously hypertensive rats by regulating microRNA-296-5p(miR-296-5p)expression.Methods The spontaneously hypertensive rats(SHR)were given 0.9％sodium chloride solution freely for 2 months,and then fed with 1％sodium chloride solution to establish the stroke model of SHR.The rat models were randomly grouped into Model group,A Ⅲ low-dose group(A Ⅲ-L group),A Ⅲ high-dose group(A Ⅲ-H group),positive drug nimodipine group(Nim group),miR-296-5p agonist group(miR-296-5p agomir group),agomir NC group,A Ⅲ-H+miR-296-5p agomir group,and A Ⅲ-H+agomir NC group,with 12 in each group.The changes in neurological symptom scores,av-erage arterial pressure,survival time,and platelet adhesion rate were detected and recorded;hema-toxylin and eosin(HE)staining was applied to detect pathological changes in the CA1 region of the rat hippocampus;quantitative reverse transcription polymerase chain reaction(qRT-PCR)was ap-plied to detect the expression of miR-296-5p in the hippocampal CA1 region.Results Compared with the NC group,the Model group showed increases in neurological symptom score,mean arterial pressure,platelet adhesion rate,miR-296-5p expression,shortened survival time,and severe pathological damage to the hippocampal CA1 area(P＜0.05);compared with the Model group,the neurological symptom scores,mean arterial pressure,platelet adhesion rate,and miR-296-5p expression in the A Ⅲ-L,A Ⅲ-H,and Nim groups decreased,the survival time was prolonged,and the pathological damage in the CA1 area of the hippocampus was alleviated(P＜0.05);compared with Model group and agomir NC group,neurological symptom score,mean arterial pressure,platelet adhesion rate and miR-296-5p expression of rats in the miR-296-5p agomir group were increased,survival time was shortened,and pathological damage in hippocampal CA1 region was aggravated(P＜0.05).compared with the A Ⅲ-H group and the AⅢ-H+agomir NC group,the neurological symptom score,average arterial pressure,platelet adhesion rate and miR-296-5p expression of rats were in-creased,the survival time was shortened,and the pathological damage in hippocampal CA1 region was serious in the AⅢ-H+miR-296-5p agomir group(P＜0.05).Conclusion A Ⅲ may treat SHR stroke by inhibiting the expression of miR-296-5p.

Objective:To explore the clinical effects of combined medial and lateral approaches in treating of calcaneal fractures combined with sustentaculum tali fractures and/or dislocations of sustentaculum tali-talus joint.Methods:Four adult cadaver specimens (8 feet) were selected, of which two (4 feet) were dissected on the medial side of the calcaneus to observe the adjacency and exposure range of sustentaculum tali. The other two specimens were simulated as medial and lateral approaches to reduce and fix calcaneal fractures. Retrospective analysis of 9 cases (9 feet) of Sanders II-IV type calcaneal fractures with combined medial and lateral approaches in the treatment of fractures and/or dislocations of sustentaculum tali-talus joint was performed. The average age was 49.9±11.3 (25-58) years. During the operation, the medial incision was made first, and the sustentaculum tali fracture was temporarily reduced and fixed to the talus. Then the lateral incision was made to expose the lateral side of the calcaneus, and the fracture fragments were reduced and fixed; the sustentaculum tali was fixed laterally with screws, and 2 cases were additionally fixed medially with absorbable rods. At the same time, six cases (8 feet) of calcaneal fractures with sustentaculum tali fractures and/or dislocations of sustentaculum tali-talus were treated with lateral approach as a control group. The lateral sides of both groups were fixed with calcaneal locking plate and implanted with demineralized bone matrix into the cavity after articular surface reduction. The B?hler and Gissane angles of the two groups of patients were measured at 1 year after operation. The American Orthopaedic Foot and Ankle Society (AOFAS) scoring system was used to evaluate the clinical efficacy.Results:The sustentaculum tali-talus joint had a shape of an inverted "V" with two divided parts. The tip of the sustentaculum tali was exposed through the front window of the posterior tibial tendon. The sustentaculum tali and the medial side of the calcaneal body was completely exposed and fixed through the window between the posterior tibial tendon and the flexor digitorum longus tendon. The postoperative incision blood loss in the combined medial and lateral approach group was 73.6±4.3 ml, which was greater than that in the lateral approach group (70.6±7.1 ml) ( t=2.18, P=0.045). The lateral incision healed in both groups. The medial incision healed delayed in 1 patient in the combined medial and lateral approach group. The fractures in the combined medial-lateral approach group and the lateral approach group were both healed. The healing duration was 12.2±2.1 weeks and 12.8±2.8 weeks, respectively, without significant difference ( t=0.50, P=0.622). The B?hler angles of the combined medial-lateral approach group and the lateral approach group were 37.0°±5.7° and 27.9°±4.0° at 1 year after operation, respectively. These values were greater than the preoperative values of 4.7°±3.4° and 3.9°±2.9° ( P<0.05), with significant difference between groups ( t=3.76, P=0.002). The Gissane angles were 133.2°±9.8° and 139.1°±9.4° respectively, which were lower than those of 172°±7.3° and 175.6°±5.6° before operation ( P<0.05). There was no significant difference between the groups ( t=1.26, P=0.226). The AOFAS score of the combined medial and lateral approach group was 93.6±4.0 points, which was higher than that of the lateral approach group (84.3±8.2 points) ( t=3.03, P=0.008). Conclusion:Intra-articular calcaneal fractures combined with a high probability of sustentaculum tali fractures and/or dislocations of sustentaculum tali-talus joint. Compared with the simple lateral approach, the use of the combined medial-lateral approach and the medial-lateral surgical sequence is beneficial to restore the calcaneal alignment and anatomic shape, especially the alignment relationship of the medial calcaneus and talus, so as to obstain better early clinical outcomes.

Objective:To investigate the serum levels, diagnosis and prognosis value of endothelin-1(ET-1) in children suffering from lung metastasis of osteosarcoma.Methods:A total of 84 children with osteosarcoma, 67 children with lung metastasis of osteosarcoma and 35 healthy people from January 1, 2013 to January 1, 2018 in Second People′s Hospital of Nanyang were retrospectively included.The serum level of ET-1 was measured by performing enzyme linked immunosorbent assay(ELISA) methods and the influencing factors of serum ET-1 levels in children with lung metastasis of osteosarcoma were conducted by Logistic regression analysis.The clinical value of ET-1 in the prediction of the incidence of lung metastasis in children with osteosarcoma was analyzed by receiver operating characteristic (ROC) curve.Forty-five children with lung metastasis of osteosarcoma were followed up for 18 months and the prognosis value of serum ET-1 levels in children with lung metastasis of osteosarcoma was evaluated by Kaplan-Meier survival analysis. Results:The serum ET-1 level in children with lung metastasis of osteosarcoma was 97.23 (65.13, 134.98) ng/L and significantly higher than osteosarcoma group 60.21 (43.12, 74.63) ng/L and healthy control group 34.45 (12.01, 63.03) ng/L, respectively ( Z=-5.671, -4.92, all P<0.05), with significant differences. Logistic regression analysis proved that lung bilateral involvement ( OR=3.449), numbers of lung metastases (more than 3)( OR=3.449), average diameter of lung metastases (more than 5 cm) ( OR=6.501) and extrapulmonary metastasis ( OR=4.369) were independent risk factors for elevated serum ET-1 levels in children developing lung metastasis of osteosarcoma.The predictive value of ET-1 in the incidence of lung metastasis in children with osteosarcoma was significant (area under ROC curve: 0.841). When the cut-off value was 94.27 ng/L, the sensitivity and specificity were 88.5% and 92.6%, respectively.Survival analysis revealed that higher levels of ET-1 was correlated with poor prognosis ( OR=3.287, 95% CI: 1.119-9.547). Conclusions:The serum levels of ET-1 in children with lung metastasis of osteosarcoma are significantly elevated.ET-1 is a serological marker for the differential diagnosis of lung metastasis of osteosarcoma.Moreover, the higher levels of ET-1 are correlated with poor prognosis in children with lung metastasis of osteosarcoma.

Objective:To explore the application effect of action-oriented education combined with Orem nursing system in patients with permanent colostomy after rectal cancer surgery.Methods:Using the convenient sampling method, a total of 120 patients with permanent colostomy after rectal cancer surgery who were admitted to Jiaozuo People's Hospital were selected as the research objects from June 2019 to June 2020. They were randomly divided into the intervention group and the control group, with 60 cases in each group. The patients in the control group received routine care and implemented action-oriented education, while patients in the intervention group were given Orem nursing system for intervention on this basis. The self-efficacy sense after the intervention and the degree of ostomy-related knowledge before and after the intervention were compared between the two groups.Results:There was significant difference in stoma related knowledge between the two groups before and after intervention ( P<0.01) . After the intervention, patients in the intervention group had better understanding of stoma-related knowledge and self-efficacy than the control group, and the differences were statistically significant ( P<0.01) . Conclusions:The implementation of action-oriented education and Orem nursing system for patients with permanent colostomy after rectal cancer surgery can improve patients' understanding of stoma-related knowledge and self-efficacy.