Aim To investigate the role of p38 mitogen-activated protein kinases(MAPKs) in genistein-induced osteoblastic differentiation of mouse bone marrow-derived mesenchymal stem cells(BMSCs).Methods Mouse BMSCs cultured in phenol red-free ?-MEM containing 10% V/V FBS,were added ?-glycerophosphate and ascorbic acid for inducing osteoblastic differentiation,and treated with 0.01~1 ?mol?L~(-1) genistein and/or SB203580 and PD98059.The temporal sequence of osteoblastic differentiation in BMSCs cultures was assayed by measuring alkaline phosphatase activity(ALP) and calcium deposition.The MAPK phosphorylation level was detected by Western-blot.Results Genistein(0.01~1 ?mol?L~(-1)) showed a dose-dependent effect on osteoblastic differentiation as evidenced by increased alkaline phosphatase(ALP) activity and calcium deposition in mouse BMSCs cultures.Genistein(1 ?mol?L~(-1))-induced osteoblastic differentiation of BMSCs was diminished by p38 MAPK inhibitor but not the p44/42 MAPK inhibitor.The effects of Genistein were associated with rapid and sustained activation of p38 MAPK in the BMSCs cultures,which was blocked by SB203580(1 ?mol?L~(-1)).In contrast,Genistein treatment resulted in inactivation of p42/44MAPK,which was further attenuated by PD98059(25 ?mol?L~(-1)).Conclusion p38 MAPK plays an important role in genistein-induced osteoblastic differentiation of mouse BMSCs cultures.

ObjectiveTo investigate the individualized treatment for traumatic liver rupture. MethodsClinical data of 58 patients with traumatic liver rupture diagnosed and treated in the CAPF Sichuan Provincial Corps Hospital between April 2011 and December 2013 were retrospectively studied. The informed consents of all patients were obtained and the local ethical committee approval had been received. Among the 58 patients, 31 were males and 27 were females with the age ranging from 2 to 76 years old and the median of 44 years old. According to the American Association for the Surgery of Trauma (AAST) grading for liver injury, 33 patients were with GradeⅡ liver injury, 16 with GradeⅢ liver injury and 9 with GradeⅣ liver injury. After admission, all patients underwent routine abdominal examination and abdominocentesis for the closed liver rupture. In addition, blood routine, coagulation function, hepatic and renal function, abdominal ultrasound and computer tomography (CT) were also examined emergently to know about the location, size and depth of liver rupture, blood loss, underlying diseases and combined injuries. The individualized treatments, including non-surgical treatment and surgical treatment were performed according to the AAST grading criteria for liver injury and the comprehensive conditions of patients.ResultsNon-surgical treatment was given to 24 patients in which 9 cases were found having obviously increased ascites by ultrasound and CT examination 3-7 d after treatment. Laparoscopic exploration was then performed on the 9 patients. During the operation, 5 were found with mild bleeding and the bleeding was stopped successfully with electrotome, cavitron ultrasonic surgical aspirator or titanium clip. And the rupture bleeding of the other 4 cases were found stopped. Two patients received CT scan 2-3 weeks after treatment and were found with encapsulated effusion near the right liver lobe and 1 case with effusion in hepatic and renal recesses. All these 3 patients underwent CT-guided puncture drainage and were cured. A total of 34 patients underwent emergency exploratory laparotomy. Among these patients, 25 underwent debridement of devitalized liver tissues and wound suture, 6 underwent regular segmental hepatectomy or hepatic lobectomy, 2 underwent hepatic artery branch ligation and wound suture, and 1 underwent greater omentum iflling and suture. After the treatment, 1 patient developed perihepatic abscess and was cured after puncture drainage. All 58 patients recovered and were discharged. Forty-ifve patients were followed up for 1-6 months. No recurrence of bleeding, bile leakage, infection, hepatic insufifciency and other complications were observed.ConclusionsIndividualized treatment can be applied for traumatic liver rupture. Patients with small and shallow liver rupture may receive non-surgical treatment under a close observation and patient with unstable vital signs and progressive bleeding at the liver rupture may receive surgical treatment. Both treatments can achieve good curative effects.

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27.8 years） were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease（ESRD）, predominantly males （6/7）. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group（P=0.013）. There was no correlation between the progression of renal disease and long-term hearing level（P>0.05）. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss（P=0.048）, and there was no correlation with the severity of hearing loss（P>0.05）. Among 11 cases, theCOL4A5mutationwas most common （8 out of 11）, but there was no significant correlation between the mutation type and hearing phenotype（P>0.05）. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.
Male ; Child ; Female ; Humans ; Nephritis, Hereditary/pathology* ; Retrospective Studies ; Kidney ; Deafness ; Hearing Loss/genetics* ; Kidney Failure, Chronic/pathology* ; Mutation