1.A case of exertional rhabdomyolysis with RYR1 gene variation
Guangpu WANG ; Yakun WANG ; Di WU ; Shoujun BAI
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(10):1330-1334
The etiology of rhabdomyolysis in adults is multifaceted,with one cause being physical exertion,termed exertional rhabdomyolysis(ERM).Characterized primarily by the destruction of muscle cells,ERM results in the release of intracellular contents into the bloodstream,leading to a spectrum of symptoms,including myalgia,dark urine,weakness,and marked elevations in serum creatine kinase(CK)and myoglobin levels.Some patients experience recurrent symptoms,persistently high serum CK levels(exceeding 50 times the normal upper limit),or unexplained severe manifestations.Despite this,the underlying pathogenesis remains elusive in numerous cases.Recent studies have implicated mutations in the RYR1 gene as a potential cause of exercise-induced ERM.This report describes a patient presenting with ERM and a heterozygous RYR1 gene missense mutation.Following treatment with fluid resuscitation,metabolic optimization,and antioxidant therapy,the patient exhibited clinical and biochemical improvement.
3.Effects and mechanism of pterostilbene on wound healing in diabetic skin ulcer model rats
Yakun LIU ; Gang LI ; Juan YAN ; Huizhi XU ; Yanjiang WU ; Shuai YOU ; Jingya NIU ; Hongjian LI ; Binggui ZHANG
China Pharmacy 2023;34(16):1967-1971
OBJECTIVE To explore the effects of pterostilbene (PTE) on wound healing in diabetic skin ulcer model rats and its mechanism. METHODS Ten SD rats were grouped into control group; after diabetic skin ulcer model of other rats was induced by giving high-fat and high-sugar diet+intraperitoneal injection of streptozotocin+cutting off the skin and subcutaneous tissue in the marked area of the back, model rats were randomly divided into model group, PTE low-dose group (40 mg/kg), PTE high-dose group (80 mg/kg), PTE high-dose+PP2 group (80 mg/kg PTE+2 mg/kg SRC inhibitor PP2), with 10 rats in each group. On the second day after modeling, the rats in each drug group were intraperitoneally injected with corresponding drug solutions, while the rats in control group and model group were intraperitoneally injected with normal saline, once a day, for 14 consecutive days. The wound healing rate of rats in each group was measured on the 7th and 14th day of administration; the contents of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) in the serum of rats were detected; the pathological changes of wound granulation tissue were observed, and the expressions of SRC/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway-related proteins in wound granulation tissue were detected. RESULTS Compared with control group, the wound healing rate, serum content of VEGF, the phosphorylation levels of SRC, MEK1/2 and ERK1/2 were decreased significantly (P<0.05), while serum contents of IL- 1β, IL-6 and TNF-α were increased significantly (P<0.05); there was obvious infiltration of inflammatory cells in the wound granulation tissue, and the number of new blood vessels decreased. Compared with model group, above indexes of PTE low-dose and high-dose groups were improved significantly (P<0.05), and the pathological injury of granulation tissue in wound was improved. PP2 significantly reversed the improvement effects of PTE on the above indexes (P<0.05). CONCLUSIONS PTE can promote the wound healing of diabetic skin ulcer model rats, the mechanism of which may be related to activating SRC/MEK/ERK signaling pathway.
4.The expression of serum miRNA-24 and miRNA-509 in patients with hepatocellular carcinoma and their correlation with prognosis
Wu PANG ; Lijiang CHEN ; Yu ZHU ; Yakun WU ; Wei ZHANG
Practical Oncology Journal 2023;37(5):411-415
Objective The objective of this study was to investigate the expression and clinical significance of serum miR-NA-24(miR-24)and miRNA-509(miR-509)in patients with hepatocellular carcinoma(HCC).Methods Ninety-four HCC patients(HCC group)who visited Suining Central Hospital in Sichuan province from January 2019 to October 2020 were select-ed,and 90 healthy subjects(control group)who underwent the physical examination center at the same time were selected.The ex-pression of miR-24 and miR-509 in human liver cancer cell lines and the serum of participants in the two groups was detected by real-time quantitative polymerase chain reaction(qRT-PCR).The correlation between miR-24 and miR-509 levels and the clinicopathological characteristics and prognosis of HCC was analyzed.Results The expression of miR-24 in the serum of HCC pa-tients was significantly higher than that of the control group(3.19±0.29vs.0.66±0.20),(t=-68.601,P<0.01),and the ex-pression of miR-509 was significantly lower than that of the control group(0.74±0.27 vs.1.24±0.28),(t=12.331,P<0.01).The expression of miR-24 in serum was positively correlated with alpha fetoprotein(AFP)level,metastasis,and TNM stage(r=0.821,0.510,0.762,P<0.01),and negatively correlated with the degree of differentiation(r=-0.771,P<0.01).The expression of miR-509 in serum was negatively correlated with AFP level,metastasis and TNM stage(r=-0.820,-0.506,-0.766,P<0.01),and negatively correlated with the degree of differentiation(r=0.775,P<0.01).Conclusion The expression of serum mir-24 is up-regulated in HCC patients,while the expression of serum mir-509 is down-regulated.Both of them are closely related to HCC metastasis and malignancy.Clinical testing of serum miR-24 and miR-509 levels in patients can help diagnose and evaluate the condition of HCC.
6.Pharmacokinetic profiles of antifungal drugs during extracorporeal membrane oxygenation life support
Dengyun FAN ; Shan LI ; Yixin LIU ; Feifei REN ; Zhenzhen YANG ; Xikun WU ; Yingchao MA ; Zhiqing ZHANG ; Yakun ZHANG
Chinese Critical Care Medicine 2022;34(1):100-104
Extracorporeal membrane oxygenation (ECMO), a kind of life support technology that can replace lung and heart function, is widely used in critical respiratory and circulatory exhaustion. Because of the serious diseases and the use of interventional catheters, patients receiving ECMO life support are often administrated with broad-spectrum antimicrobial agents, which increase the risk of fungal infection. Fungal infection during ECMO can increase mortality. How to effectively control fungal infection is a thorny problem faced by clinicians. During the treatment of ECMO, the patient's physiological status, ECMO oxygenation membrane, circulation pipeline and other factors may change the pharmacokinetic profiles of antifungal drugs, thereby affect the clinical efficacy of drugs. This artical reviews the pharmacokinetic characteristics of antifungal drugs during ECMO support, in order to provide references for clinical antifungal treatment.
7.Mechanism of tanshinone ⅡA inhibiting myocardial remodeling by Galectin-3
Meiqi ZHANG ; Kang CHENG ; Limei YU ; Weihua WU ; Yakun WANG ; Yun CHEN
Chinese Critical Care Medicine 2022;34(6):640-645
Objective:To explore the effect of tanshinone ⅡA on myocardial remodeling in ischemia/reperfusion (I/R)-induced heart failure of rodent model.Methods:① In vivo, 30 SD rats were randomly divided into sham operation, heart failure and tanshinone ⅡA treatment group, with 10 rats in each group. The I/R model was established by ligating the left coronary artery until ST segment elevation for 30 minutes, then the ligation was removed for 2 hours as reperfusion. In the sham operation group, the rat chest was opened without artery ligation. Three days after model establishment, tanshinone ⅡA (10 mg/kg) were given intraperitoneal injected in tanshinone ⅡA group for 9 weeks. In the other two groups, normal saline was administrated in the same way. The behavioral manifestations of the rats in each group were observed; hemodynamic indexes were evaluated; Masson staining was performed to observe the degree of myocardial fibrosis; enzyme linked immunosorbent assay (ELISA) was used to detect the content of Galectin-3 in myocardial tissue; quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the expressions of collagenⅢ, collagenⅠ, matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase (TIMP-1). ② In vitro, rats primary cardiac fibroblasts were extracted and isolated, and divided into blank control group, angiotensinⅡ group (7-10 mmol/L angiotensinⅡ) and angiotensinⅡ+ tanshinoneⅡA group (7-10 mmol/L angiotensinⅡ+ 5-10 mmol/L tanshinone ⅡA). At 24 hours and 48 hours of culture, the cell proliferation in each group was detected by methyl thiazolyl tetrazolium (MTT); the expressions of collagenⅢ, collagenⅠ, MMP-2 and TIMP-1 were detected by qRT-PCR; the content of Galectin-3 in cardiac fibroblasts was detected by ELSIA. Results:① In vivo, the rats' activity status, hair conformity and food intake were ranked from good to bad in order of sham operation group, tanshinone ⅡA group and heart failure model group. Compared with the sham-operated group, the heart rate (HR) of the rats in the heart failure model group was significantly decreased and the heart function was significantly impaired. The mRNA and protein expression of collagenⅠ, collagenⅢ, TIMP-1 and Galectin-3 content were significantly increased, while the mRNA and protein expression of MMP-2 were significantly decreased. Compared with the heart failure model group, rats in the tanshinone ⅡA group showed significantly higher HR and improved cardiac function, significantly lower mRNA expression of collagenⅠ and collagenⅢ, significantly lower mRNA and protein expression of TIMP-1 and Galectin-3, and significantly higher mRNA and protein expression of MMP-2, and the most obvious changes were in the 9th weeks of modeling [collagenⅠ mRNA (2 -ΔΔCt): 4.70±1.19 vs. 10.21±1.62, collagenⅢ mRNA (2 -ΔΔCt): 3.03±0.46 vs. 13.84±1.93, TIMP-1 mRNA (2 -ΔΔCt): 1.90±0.19 vs. 4.55±0.43, TIMP-1/GAPDH: 0.33±0.04 vs. 0.67±0.05, Galectin-3 (ng/L): 489.93±79.30 vs. 821.72±94.09, MMP-2 mRNA (2 -ΔΔCt): 0.37±0.07 vs. 0.03±0.01, MMP-2/GAPDH: 0.69±0.09 vs. 0.21±0.04, all P < 0.05]. Masson staining showed that myocardial tissue fibrosis was obvious in the heart failure group, and the degree of fibrosis in the tanshinoneⅡA group was reduced. ② In vitro, compared with the blank control group, the proliferation rate, collagenⅠ, collagen Ⅲ and TIMP-1 expression and Galectin-3 content of myocardial fibroblasts were significantly increased, and MMP-2 expression was significantly decreased in the angiotensin group at 24 h and 48 h of culture. Compared with the angiotensin group, the proliferation rate of cardiac fibroblasts and the expression of collagenⅠ, collagen Ⅲ and TIMP-1 and the content of Galectin-3 were significantly decreased, and the expression of MMP-2 mRNA was significantly increased in the angiotensin + tanshinone ⅡA group, and the most significant changes were at 48 hours of culture [proliferation rate: (57.0±3.7)% vs. (67.0±2.4)%, collagenⅠmRNA (2 -ΔΔCt): 551.43±67.10 vs. 871.48±12.25, collagenⅢ mRNA (2 -ΔΔCt): 233.76±18.73 vs. 385.51±31.35, TIMP-1 mRNA (2 -ΔΔCt): 238.69±17.37 vs. 351.84±26.17, Galectin-3 (ng/L): 283.76±28.73 vs. 415.51±31.35, MMP-2 mRNA (2 -ΔΔCt): 108.54±12.10 vs. 51.47±6.25, all P < 0.05]. Conclusion:Tanshinone ⅡA can improve cardiac function, inhibit myocardial fibrosis and improve myocardial remodeling in rats with I/R-induced heart failure.
8.MiR-30a targeting Keap1 in relieving cerebral ischemia-reperfusion injury in rats
Journal of Chinese Physician 2021;23(1):63-67
Objective:To study the function and mechanism of miR-30a in rat cerebral ischemia-reperfusion (I/R) injury.Methods:The middle cerebral artery occlusion (MCAO) model was established by intravascular suture method, and the expression of miR-30a in brain tissue was detected by real-time quantitative polymerase chain reaction (qRT-PCR). After intracerebroventricular injection of miR-30a lentivirus, the infarct area was detected by 2, 3, 5-triphenyltetrazole chloride (TTC) staining, the neurological deficit was detected by Bederson method, and the concentration of neurotrophin-3 (3-NT) and nitric oxide (NO) in brain tissue was detected by enzyme-linked immunosorbent assay (ELISA). The protein levels of kelch like ECH associated protein 1 (Keap1), NF-E2-related factor 2 (Nrf-2) and hemeoxygenase-1 (HO-1) in brain tissue were detected by Western blot. Double luciferase reporter assay was used to detect the targeting relationship between miR-30a and Keap1.Results:Compared with sham operation group, the expression of miR-30a was down-regulated in a time-dependent manner after I/R. The overexpression of miR-30a can reduce the area of cerebral infarction tissue at the pathological level, the degree of neurological impairment at the functional level, the 3-NT, NO and Keap1 at the molecular level, and enhance the expression of Nrf2 and HO-1. The dual luciferase reporter assay also showed that miR-30a could bind to Keap1 mRNA.Conclusions:The expression of miR-30a was down-regulated in MCAO rat brain tissue, and miR-30a could attenuate cerebral I/R injury in rats by targeting Keap1.
9.Diagnosis and treatment progress of acquired immunologic deficiency syndrome-related lymphoma
Yulin ZHANG ; Yakun TIAN ; Caiping GUO ; Hao WU
Journal of Leukemia & Lymphoma 2018;27(6):376-379
Malignancy is one of the most important complications of acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV) infection and destruction of host CD4-positive T lymphocytes. Lymphoma ranks first in AIDS-related malignancies. The clinical features of lymphoma patients infected with HIV are different from non-HIV infected patients. The host immune condition in anti-lymphoma chemotherapy also needs to be considered. This paper reviews the clinical characteristics of AIDS-related lymphoma and the attention in anti-lymphoma therapy according to the latest international research findings and related guidelines.
10.Application of radiofrequency ablation for traumatic splenic preservation
Tao ZHOU ; Yinsheng TIAN ; Yakun WU
Chinese Journal of General Surgery 2016;31(2):113-116
Objective To evaluate radiofrequency ablation (RFA) assisted splenic preservation in traumatic splenic rupture.Methods Data of 70 cases with traumatic rupture of the spleen at our hospital from Septembcr 2009 to June 2014 were retrospectively analysed.Patients were divided into two groups according to different surgical methods,namely,RFA group (n =35) and control conventional surgery group (n =35).Results In the RFA group,34 cases underwent successful spleen preserving operation,the success rate was 97%.In control group,26/35 cases received splenic preservation operations successfully,the success rate was 74% (26/35) (x2 =7.467,P < 0.05).Average operation time,bleeding during operation and intra-operative transfusion in RFA group were (80 ± 22) min,(116 ± 66) ml and 5 cases,rcspectively,significantly better than that in control of group.(122 ± 80) min,(237 ± 192) ml and 13 cases,respectively (t =4.58,t =3.324;x2 =4.786,P < 0.05).Postoperative bleeding,hospital stay and cases receiving transfusion in RFA group were (113 ± 72)ml,(7.8 ± 1.2) d and 2 cases,respectively,which were remarkably better than those in control group of (246 ± 140) ml,(10.2 ± 1.6) d and 8 cases (t =3.267,t =4.536;x2 =4.9;P < 0.05).Postoperative complications in the two groups were similar (x2 =0.913,P > 0.05).Conclusions Compared with traditional spleen preserving surgery,RFA is simple and effective.It can greatly reduce the difficulty and risks of splenic preservation surgery,increasing the preservation of ruptured spleen.

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