BACKGROUND:Exosomes can be detected in synovial fluid and plasma at levels that vary with the progression of osteoarthritis in patients with osteoarthritis,and may play a relieving role in the local inflammation of osteoarthritis,cartilage calcification,and osteoarthritic joint degradation. OBJECTIVE:To comprehensively understand the function and mechanism of exosomes from different stem cells in the diagnosis and treatment of osteoarthritis,and to present the prospects and challenges of exosome therapy for osteoarthritis. METHODS:We searched the articles published from October 2003 to October 2023 included in PubMed and CNKI databases with the keywords of"exosomes,osteoarthritis,mesenchymal stem cells,stem cells"in Chinese and English,respectively.A total of 99 articles were finally included for review. RESULTS AND CONCLUSION:The appearance of exosomes brings hope to the diagnosis and treatment of osteoarthritis.The differences of RNA,protein,and lipid content in exosomes can be used as biomarkers for the diagnosis of osteoarthritis.At the same time,exosomes from various stem cells can effectively protect chondrocytes,relieve inflammation,maintain cartilage matrix metabolism,and regulate angiogenesis and subchondral bone remodeling,showing excellent potential in the treatment of osteoarthritis.The engineered exosomes break through the traditional limitations and enhance the specificity and efficiency of treatment by modulating the expression of specific non-coding RNA,providing a new strategy for the treatment of osteoarthritis.

Objective To investigate the impact of donor kidney histopathological lesions on the risk of BK virus (BKV) infection and progression after kidney transplantation. Methods A retrospective analysis was conducted on the clinical data of 326 kidney transplant recipients from deceased donors at the Department of Kidney Transplantation, the First Affiliated Hospital of Zhengzhou University, from January 2019 to June 2020. The recipients were divided into two groups based on whether BKV infection occurred after kidney transplantation: the BKV infection group (145 cases) and the non-BKV infection group (181 cases). The correlation between donor kidney histopathological findings from zero-hour biopsy and BKV infection, as well as the impact on the risk and progression of BKV infection, was analyzed. Results The incidence of BKV infection among the 326 kidney transplant recipients was 44.5% (145/326). The clearance rate of BKV after infection was 82.1% (119/145), while 17.9% (26/145) progressed to BKV viremia. Among the 326 qualified kidney biopsy specimens, 32 cases showed mild tubular atrophy, 324 cases had mild acute tubular injury, 27 cases exhibited mild hyaline arteriosclerosis, 10 cases had moderate to severe hyaline arteriosclerosis, 7 cases showed mild interstitial inflammation, 23 cases had mild interstitial fibrosis, 6 cases exhibited mild arterial intimal fibrosis, and 1 case had moderate to severe arterial intimal fibrosis. Multivariate logistic regression analysis revealed that male recipients, donor age and tubular atrophy were independent risk factors for BKV infection (all P<0.05). Tubular atrophy was also an independent risk factor for the progression from BKV uria to BKV viremia (P<0.05). Conclusions Donor kidney histopathological lesions have a certain impact on BKV infection and progression after kidney transplantation. Patients with more severe tubular atrophy in donor kidneys have a higher risk of BKV infection after kidney transplantation and are more likely to progress to BKV viremia.

Phase Ⅰ clinical trials play a crucial role in the research and development of new drugs, serving as the initial studies to assess their safety, tolerability, effectiveness, and pharmacokinetic properties in humans. These trials involve uncertainties regarding safety and efficacy. Comprehensive management of all aspects of phase Ⅰ clinical trials for anti-tumor drugs is crucial to protect the rights and safety of participants. This article provides an in-depth analysis of the key points and precautions necessary for effective quality control throughout the process. The analysis is informed by guidelines such as the “Good Clinical Practice for Drugs” “Key Points and Judgment Principles for Drug Registration Verification” “Key Points and Judgment Principles for Supervision and Inspection of Drug Clinical Trial Institutions” and the standard operating procedures for quality control of the center. Topics discussed include informed consent, inclusion criteria, experimental drugs, biological samples, adverse events, and serious adverse events. The goal is to standardize quality control in phase Ⅰ clinical trials of anti-tumor drugs, ensure the authenticity and reliability of clinical trial data, and protect the rights and safety of participants.

Objective To investigate the features of surface electromyography （sEMG） signals in patients with lower limb dystonia and hepatolenticular degeneration， also known as Wilson disease （WD）， as well as the feasibility of sEMG as an assessment tool for lower limb dystonia in WD. Methods A total of 36 WD patients with lower limb dystonia （observation group） and 20 WD patients without lower limb dystonia （control group） were enrolled， and 20 normal subjects were enrolled as healthy group. The sEMG technique was used to measure the AEMG， MF， MPF， and iEMG values of the anterior tibial muscle， the gastrocnemius muscle， and the rectus femoris muscle in the walking state， and a Spearman’s rank correlation analysis was used to investigate the correlation of the iEMG value of the rectus femoris muscle in both lower limbs with Activities of Daily Living （ADL）， the neurological subscale of Unified Wilson’s Disease Rating Scale （UWDRS-I）， the Burke-Fahn-Marsden Dystonia Rating Scale （BFMDRS）， the Modified Ashworth Scale， and 10-meter walking time. The observation group and the healthy group were compared in terms of the symmetry index （SI） of the same-named muscles on both sides， and the correlation of SI value with scale scores and walking time was analyzed for the observation group. Results There were significant differences in iEMG values and all electromyography values of the rectus femoris muscle between the three groups （P<0.05）. In the observation group， the iEMG value of the rectus femoris muscle was negatively correlated with the ADL scale and was positively correlated with dystonia-related scales and 10-meter walking time， suggesting that the iEMG value of the rectus femoris muscle could reflect the severity of lower limb dystonia in WD. Meanwhile， there were significant differences in the SI values of bilateral muscles between the observation group and the healthy group （P<0.05）， and for the observation group， the SI values of the muscles were negatively correlated with the ADL scale and were positively correlated with other variables， suggesting that lower limb dystonia in WD was asymmetric， and the degree of asymmetry was positively correlated with the degree of dystonia. Conclusion This study shows that sEMG has a certain application value in assessing lower limb dystonia in WD patients and can be used as an assessment tool for lower limb dystonia in WD.
Dystonia

Hepatolenticular degeneration （HLD），also known as Wilson disease (WD) is an uncommon hereditary disorder of the nervous system， characterized by hepatic impairment， extrapyramidal manifestations， psychiatric symptoms， and renal dysfunction， while impaired vision is a rare comorbidity. This article conducts a retrospective analysis of visual acuity changes， treatment， and prognosis of a female patient， aged 22 years， who were diagnosed with HLD complicated by bilateral neuritis in an affiliated hospital of Anhui University of Chinese Medicine in 2022， and a literature review was performed. The findings suggest that impaired vision is a rare manifestation of HLD. Ophthalmologists should consider the possibility of HLD in patients with optic atrophy and optic neuritis， and early intravenous administration of methylprednisolone may help to improve prognosis.

Objective: To explore the efficacy of transcystoscopic holmium laser sieve-shaped fenestration in the treatment of ureteral cysts in children. Methods: The clinical data of 41 children with ureteral cysts treated in our hospital during Jan.2019 and Dec.2023 were retrospectively analyzed.All children received this surgery.The perioperative indicators and postoperative outcomes were recorded. Results: All operations were successful, the average operation time being (32.20±11.49) min.During the 12-month follow-up, the cysts were reduced or the obstructive symptoms were relieved in 31 cases, and the cysts completely disappeared in 6 cases.Vesicoureteral reflux (VUR) developed in 4 cases, 1 of which had grade Ⅱ VUR with no obvious symptoms and received conservative treatment.Repeated urinary tract infections developed in 2 cases; obstructive symptoms remained unchanged in 1 case; these 3 cases received vesicoureteral replantation.Two days before operation and 3 months after operation, the ureter diameter was (9.95±2.38) mm and (7.41±3.39) mm (t=3.16, P＜0.05), the anteroposterior diameter of the renal pelvis was (13.32±2.63) mm and (9.07±3.02) mm (t=6.86, P＜0.01). Conclusion: Transcystoscopic holmium laser sieve-shaped fenestration for children with ureteral cysts has good efficacy, little trauma and few complications.It can quickly relieve obstructive symptoms and can be used as the initial treatment of ureteral cysts.

Fluorine is a common chemical element. Excessive intake of fluoride can lead to fluorosis. Fluoride easily passes through the blood-brain barrier and accumulates in different brain regions, causing pathological changes in brain tissue. It leads to adverse effects on neuronal metabolism, enzyme, protein function, neurotransmitters, and redox homeostasis, and subsequently neuronal damage and neurodegenerative diseases in humans and experimental animals. This paper reviewed the effects and important mechanisms of fluoride on neurological function and behavior, involving mitochondrial toxicity, oxidative stress, cell apoptosis and autophagy, and activation of pro-inflammatory factors. It provided a reference for further studying the mechanisms of brain damage induced by fluorosis.

Objective: To analyze the adverse treatment outcome status and spatio temporal characteristics of pulmonary tuberculosis cases among students in Qinghai Province, providing a reference basis for pulmonary tuberculosis prevention and control in schools. Methods: The data of student pulmonary tuberculosis cases during 2013-2023 in Qinghai Province were obtained through the "National Tuberculosis Management Information System", and the treatment outcome was retrospectively analyzed. The Joinpoint model was applied to analyze the adverse outcome rate trend. Global and local spatial autocorrelation analysis, and spatiotemporal scan cluster analysis were conducted on the adverse outcome rate of pulmonary tuberculosis among students in Qinghai Province. Results: During 2013-2023, 488 cases of adverse outcomes were reported among 6 155 students with pulmonary tuberculosis in Qinghai Province, with an adverse outcome rate of 7.93%. The reporting adverse outcome rate of pulmonary tuberculosis among students showed a downward trend from 2013 to 2023 (APC=-16.20, t =-3.89, P <0.05). The results of spatial autocorrelation showed that the adverse outcome rate of pulmonary tuberculosis was Moran s I >0 among students in Qinghai Province. Among them, there was a spatially positive correlation in the adverse outcome rate of pulmonary tuberculosis among students in 2020, 2021 and 2022(all Z >1.96, all P <0.05). The results of clustering and outlier analysis in local spatial autocorrelation showed that the areas with high high aggregation were mainly concentrated in Yushu Prefecture(Zhiduo County, Zaduo County, Nangqian County, Yushu City), Huangnan Prefecture (Zeku County, Henan County) and Hainan Prefecture (Tongde County). The low low concentration areas were distributed in Haidong City, Xining City, Haibei Prefecture (Gangcha County, Qilian County), Haixi Prefecture (Tianjun County, Ulan County), Hainan Prefecture (Gonghe County, Guide County) and Huangnan Prefecture (Tongren City, Jianzha County). The spatio temporal scanning showed that a total of two possible aggregation areas had been detected. Among them, the first level aggregation area composed of 10 counties and districts in Yushu Prefecture and Guoluo Prefecture of Qinghai Province, and the cluster radius was 658.09 km, the RR was 10.58 , and the LLR was 305.91; the second level aggregation area was composed of 16 counties and districts in Hainan Prefecture, Haixi Prefecture, Huangnan Prefecture and Guoluo Prefecture, and the cluster radius was 407.02 km, the RR was 9.83, and the LLR was 152.48 (both P <0.05). Conclusions The reporting rates of adverse treatment outcome of pulmonary tuberculosis cases among students in Qinghai Province remain relatively high and unevenly distribute throughout the province. Supervision should be strengthened to improve cases compliance,and to reduce student pulmonary tuberculosis adverse treatment outcomes incidence.

Objective To design and synthesize derivatives of oleanolic acid and ursolic acid, and investigate their anti-hepatitis C virus （HCV） activity along with that of common triterpenoid acids. To explore the structure-activity relationship and provide a reference for the research of anti-HCV drugs derived from natural products through obtaining compounds with higher activity. Methods Oleanolic acid and ursolic acid were directly reacted with corresponding amines using PyBOP as a condensing agent in the presence of DIEA. Alternatively, the target compounds were prepared through PCC oxidation followed by the Baeyer-Villiger reaction catalyzed by m-CPBA. In vitro anti-HCV activity was tested using the HCVcc infection model. Molecular docking was performed by Autodock software to investigate the interaction between the active compounds and HCV NS5B. Results Oleanolic acid, glycyrrhetinic acid, ursolic acid, and asiatic acid all exhibited certain anti-HCV effects. Specifically, oleanolic acid derivatives OA2-OA4, OA6, and OA7, as well as ursolic acid derivatives UA1 and UA2, demonstrated superior anti-HCV activity compared to their parent compounds. Preliminary structure-activity relationship analysis revealed that introducing a bulky group to 28-COOH of oleanolic acid and ursolic acid enhanced their activity. Molecular docking results demonstrated that the active compounds could stably bind to HCV NS5B, thereby exhibiting antiviral activity. Conclusion Pentacyclic triterpenoids possessed anti-HCV effects, and their derivatives coud be synthesized to obtain more active compounds. The anti-HCV mechanism of these compounds may be associated with their inhibition of NS5B.

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