BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Ovarian cancer is a common gynecologic malignancy.In clinical practice,recurrent ovarian cancer is mainly classified into two categories on the basis of platinum-free interval,platinum-resistant and platinum-sensitive,corresponding to different treatment modalities and prognoses.The treatment of platinum-resistant ovarian cancer is challenging.Some scholars have pointed out limitations in the binary classification of platinum-free interval.In this article,the classification of recurrent ovarian cancer,the treatment challenges of platinum-resistant ovarian cancer,the limitations of the platinum-free interval binary classification,and new classification perspectives were reviewed to help physicians enhance their understanding on the research progress in ovarian cancer classification and develop more effective treatment strategies.

Objective:To analyze long-term prognosis and influencing factors of recurrence in vocal fold leukoplakia treated by endoscopic cordectomy with CO 2 laser. Methods:A retrospective review was conducted on 599 patients with vocal fold leukoplakia [566 males and 33 females, aged 17-84 years (median age 55 years)], undergoing endoscopic cordectomy by CO 2 laser under general anesthesia at the Department of Otorhinolaryngology Head and Neck Surgery of Beijing Tongren Hospital, Capital Medical University, from January 2000 to December 2023. The study analyzed the clinical features, pathological grade, surgical methods, postoperative voice function, recurrence, malignant changes and analyzed the long-term efficacy and and its influencing factors. The patients were followed up for a duration of 6-249 months postoperatively, with a median follow-up time of 48 months. SPSS 20.0 software was used for statistical analysis. Results:Among the 599 patients, the histopathological grades included simple squamous cell hyperplasia in ( n=264, 44.08%), mild dysplasia ( n=96, 16.03%), moderate dysplasia ( n=74, 12.35%), severe dysplasia( n=43, 7.81%), carcinoma in situ( n=35, 5.84%), and carcinoma in situ with microinvasion( n=87, 14.52%). The 3-year and 5-year overall recurrence rates were 12.91% and 16.00%, respectively. In patients with precancerous lesion, 3.91% of recurrences presented with an upgraded pathologic grade and 2.34% evolved into carcinoma. The risk of recurrence was higher in lesions involving the anterior commissure, larger lesions, significant reduction/absence of mucosal waves, neovascularization/suspected neovascularization, and pathology of dysplasia/carcinoma in situ/carcinoma in situ with microinvasion( F=44.76,21.54,11.55,8.78,23.20,respectively, P<0.05). Additionally, patients with recurrent disease exhibited higher reflux symptom index scores compared to those without recurrence. Exophytic lesion characteristics and the inability to cease smoking postoperatively were identified as independent risk factors for recurrence with an upgraded pathological grade, with odds ratios of 8.675 and 11.380 times greater than those with non-exophytic lesions and successful smoking cessation, respectively. At the 6-months postoperative assessment, patients who underwent subepithelial cordectomy (typeⅠ) demonstrated a statistically significant increase in fundamental frequency ( t=-3.38, P<0.05), and while other voice acoustic parameters were not significantly different.Conversely, those who underwent transmuscular cordectomy (TypeⅢ) exhibited significant alterations in multiple voice acoustic parameters when compared to preoperative values ( P<0.05). Furthermore, postoperative vocal fold adhesions developed in 84 patients with 13 of these individuals requiring surgical intervention for adhesion release. Conclusions:Lesions involving the anterior commissure, larger lesions, pathology of dysplasia/carcinoma in situ/carcinoma in situ with microinfiltration, significant reduction/absence of vocal fold mucosal waves, and neovascularization visible under NBI are indicative of an increased risk of recurrence, whereas exophytic lesions and the inability to cease smoking postoperatively significantly increase the risk of recurrence with elevated pathologic grade. Recovery of postoperative voice quality is procedure-dependent, underscoring the importance of surgical approach selection in the management of vocal fold leukoplakia.

Objective:To evaluate the curative effect of Sun's procedure using sutureless artificial blood vessel replacement technique on acute type A aortic dissection.Methods:Retrospective analysis was performed on 40 patients with acute type A aortic dissection who underwent Sun's procedure in The First People's Hospital of Nanning from May 2019 to April 2023. According to the surgical method, the patients were divided into sutureless group (20 cases) and traditional group (20 cases).The time of stopping circulation, cardiopulmonary bypass, recovery time, intubation time, blood loss 12 h after operation, cerebral infarction and acute renal failure were compared between the two groups.Patients older than 70 years, patients with preoperative malperfusion syndrome, or patients who did not undergo Sun's procedure were excluded.Results:The time of stopping circulation[( 13.6±3.3)min vs. ( 28.2±5.6)min, P<0.001] and the time of cardiopulmonary bypass[(116.0±34.8)min vs.(219.1±46.3 )min, P<0.001]and blood loss at 12 h after operation[( 474.5±301.0)ml vs. (422.7±389.8)ml, P<0.001] in the sutureless group were significantly lower than those in the traditional group.All patients survived and were discharged from hospital. There were no significant differences in recovery time, intubation time, cerebral infarction and acute renal failure between the two groups. Conclusion:Sutureless artificial blood vessel replacement technique can significantly shorten the time of stopping circulation and cardiopulmonary bypass, effectively protect the function of the whole body organs, and reduce the occurrence of postoperative complications.Moreover, it is easy to carry out in primary hospitals, and it is a safe and effective new surgical strategy for treating acute type A aortic dissection with Sun's surgery.

Objective:To explore the comparison of imaging characteristics and diagnostic value between ultrasound and CT in patients with pulmonary tuberculosis in Tibetan population in plateau region.Methods:From May 2022 to November 2023,a total of 100 patients with pulmonary tuberculosis of Tibetan population in plateau region,who admitted to Qinghai Provincial Hospital of Traditional Chinese Medicine,were selected as the study objects.All of them were examined by ultrasound and CT.The ultrasonic imaging characteristics of the lesions of patients with pulmonary tuberculosis in plateau region were dynamically observed.And then,the diagnostic effects of ultrasound and CT on pulmonary tuberculosis in the Tibetan population in the plateau region were compared.Results:There was no significant difference in the positive rate of pulmonary tuberculosis in Tibetan population of plateau region between ultrasound and CT examinations(x2=0.421,P＞0.05).The diagnostic sensitivity,diagnostic specificity and Yoden index of ultrasound diagnosis were respectively 97.80%,44.44%and 42.24%,and these of CT diagnosis were respectively 96.77%,42.86%and 39.63%,and the differences were not significant(x2=0.184,0.004,0.272,P＞0.05),respectively.There was no significant difference in detection rate of the distribution of pulmonary tuberculosis lesions in Tibetan population in plateau region between ultrasound and CT examinations(x2=2.011,P＞0.05).There were no significant differences in the detection rates of atelectasis,cavity,calcification and accompany of pleural effusion between ultrasound and CT examinations in patients with pulmonary tuberculosis in Tibetan population in plateau region(x2=0.190,0.197,0.190,0.046,P＞0.05).Conclusion:There are no significant differences in positive detection rate,the detection rate of the distribution of diseased lung lobes,the detection rates of the complication of pulmonary tuberculosis or associated signs such as atelectasis,cavity,calcification and accompany of pleural effusion between ultrasound and CT examinations.The medical resource of plateau region is lack,which is shorter of large examination equipment.Therefore,using ultrasound examination to conduct general survey and preliminary diagnosis for pulmonary tuberculosis is more suitable to the plateau region that lacks CT equipment or is affected by electricity

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To conduct a scoping review of virtual reality motor sensing exercise in the elderly with dementia,so as to identify the types of intervention,outcome indicators,evaluation tools and application effects of virtual reality motor sensing exercise and provide guidance for future research.Methods A literature search was performed in the PubMed,Embase,CINAHL,Web of Science,Cochrane Library,CNKI,Wanfang,VIP,and CMB databases to identify relevant studies.The search period is from the establishment of databases to October 15,2023.The included studies were summarized and analyzed.Results A total of 18 articles were included in this study,including 14 randomised controlled trials,one class-experimental study and three mixed studies involving a total of 1,054 elderly dementia patients.The types of virtual reality motor sensing exercise included motor sensing interactive games,interactive bicycle riding,remote game exercise,Wii Fit exercise and virtual reality environment exercise.The outcome indicators involve 4 aspects of physical indicators,psychological indicators,cognitive function and quality of life.Conclusion Virtual reality motor sensing exercise is feasible and effective in the elderly with dementia.However,large sample and high-quality randomized controlled trials are still needed in the future to verify the feasibility and application effect of virtual reality exercise in the elderly with dementia,so as to provide evidence-based basis for formulating the best exercise intervention program for the elderly with dementia.

Objective To explore the ideas,methods and pathways for the registration of Chinese medicine prescriptions in overseas countries,to form a strategy for overseas registration of Chinese medicine,and to provide technical support and reference for China's Chinese medicine prescriptions to go abroad.Methods Five representative countries were selected to form corresponding expert teams and exchange platforms for international cooperation.The laws,regulations,rules,standards,specifications and technical guidance documents related to Chinese medicine prescription preparations of the target countries were used as pathway research materials,and the documents were translated directly,naturalized,proofread and diagrammed,and a problem-oriented mechanism for consultation with domestic and international experts was established to form a pathway for overseas registration of Chinese medicine prescription preparations.Results The path for standardization of overseas registration of Chinese medicines was clarified,and the detailed registration paths and corresponding work strategies of Chinese medicines in five countries were formulated with flow charts,tables and explanatory texts.Conclusion By developing standardized registration pathways for traditional Chinese medicine in target countries,reference can be provided for the internationalization of Chinese herbal formula preparations.