1.Targeting STAT3 alleviates peritoneal fibrosis by regulating glycolysis and mesothelial-mesenchymal transition
Qilei DENG ; Jiao FU ; Nan LI ; Mengmeng HE ; Dake HUANG ; Pei ZHANG
Acta Universitatis Medicinalis Anhui 2024;59(4):647-653
Objective To study the effect and mechanism of high glucose on mesothelial-mesenchymal transition(MMT)of peritoneal mesothelial cells(HMrSV5),and the protective effect of pharmacological blocking of signal transducer and activator of transcription 3(STAT3)on rat peritoneal fibrosis(PF)model.Methods The animals were divided into three groups:the sham group,the model group,and the STAT3 inhibitor group.A miniature per-itoneal dialysis catheter was implanted under the dorsal skin of rat and the rat peritoneal fibrosis model was induced by daily injection of high glucose dialysate.After 10 weeks,HE staining was used to evaluate the histology of the peritoneum,and the level of transforming growth factor-β1(TGF-β1)in the peritoneum was measured by immuno-histochemistry.HMrSV5 was cultured in high glucose and the optimal stimulation concentration of high glucose was determined by Western blot.High glucose was used to stimulate HMrSV5 after successful transfection with si-STAT3 and Western blot was used to measure the protein level of STAT3,p-STAT3,and the key enzymes of glycol-ysis 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3)and lactate dehydrogenase A(LDHA).Results HE staining showed that administration of STAT3 inhibitor(BP-1-102)could inhibit the thickening of subperitoneal tissue and the proliferation of vessels in HG dialysis rats.The expression of TGF-β1 in the rats perito-neum of the model group was significantly higher than that in the sham group,and the level of TGF-β1 was marked-ly lower in the STAT3 inhibitor group compared to the model group(P<0.05).Compared to the control group,high glucose induced the up-regulation of α-smooth muscle actin(α-SMA),the down-regulation of E-cadherin and STAT3 activation in HMrSV5(P<0.05).Mesothelial cells treated with high glucose also exhibited high expres-sion of the key enzymes of glycolysis(PFKFB3,LDHA)(P<0.05),and si-STAT3 can effectively inhibit the overexpression of PFKFB3 and LDHA induced by high glucose(P<0.05).Conclusion STAT3 is involved in high glucose-induced HMrSV5 hyperglycolysis and MMT,and targeting STAT3 alleviates peritoneal fibrosis and an-giogenesis during peritoneal dialysis treatment in rats.
2.Effect of hypothyroidism in pregnancy on cognitive function in rat offspring
Yawei ZHANG ; Yuanyuan CHENG ; Min XU ; Dake HUANG ; Datong DENG
Acta Universitatis Medicinalis Anhui 2024;59(6):1035-1039
Objective To investigate the effects of hypothyroidism and drug intervention on the cognitive function of rat offspring through the establishment of a rat model of experimental hypothyroidism in pregnancy.Methods A to-tal of 20 SD female rats were randomly divided into control group(CON group)and hypothyroid group(PTU group).The hypothyroid model was established by propylthiouracil(PTU),the thyroid hormone levels of female mice were detected by electrochemiluminescence immunoassay,and the differences between the two groups were compared.After successful modeling,the male mice were mated in cages,and the hypothyroid group was randomly divided into no intervention group(group Ⅰ),first trimester intervention group(group Ⅱ)and second and third tri-mester intervention group(group Ⅲ).The Morris water maze(MWM)experiment was used to test the learning and memory ability of the rats.The morphological structure of hippocampal neurons,the expression of nucleoprotein(NeuN)and synapse-associated protein(SYN)in mature neurons were observed by hematoxylin-eosin staining(HE),Nissl staining and immunohistochemistry.Results ① Compared with the CON group,the female mice in the PTU group had a significant increase in TSH and a significant decrease in FT4(P<0.05).② In the positio-ning navigation test,the evasion latency of the pups in each group was gradually shortened.On the 5th day,the in-cubation period of group Ⅰ was significantly longer than that of groups CON,Ⅱ,Ⅲ(P<0.05).There was little change between groups Ⅱ and Ⅲ and CON groups(P>0.05).③ The residence time of group Ⅱ was significantly different from that in group Ⅰ during the space exploration stage(P<0.05).There was a significant difference be-tween the number of pups crossing the platform in group Ⅰ and groups CON,Ⅱ and Ⅲ(P<0.05).④ There was no significant difference between HE staining and Nissl staining in hippocampal tissues of rats in each group.How-ever,compared with the CON group,the average absorbance of NeuN and SYN proteins in the hippocampus of mice in groups Ⅰ,Ⅱ and Ⅲ was significantly reduced(P<0.05).Conclusion Hypothyroidism will have adverse effects on the cognitive function and hippocampal neuron development of pregnant rats,and the effects of interven-tion on the cognitive function of offspring at different stages of pregnancy are different,the earlier the intervention,the smaller the damage to cognitive function.
3.2021 classification and reduction techniques of irreducible intertrochanteric fractures
Dake TONG ; Wenbin DING ; Guangchao WANG ; Kang LIU ; Chen DING ; Qianyun HE ; Yang TANG ; Xin ZHANG ; Anwaier DILIXIATI· ; Fang JI
Chinese Journal of Orthopaedic Trauma 2022;24(3):238-246
Objective:To revise the 2017 classification of irreducible intertrochanteric fractures and summarize reduction techniques of 2021 classification.Methods:A retrospective analysis was conducted of the 17 patients with irreducible intertrochanteric fracture who had been treated at Department of Orthopaedic Surgery, The Ninth People's Hospital of Shanghai, Shanghai Jiaotong University School of Medicine from January 2015 to December 2019. They were 7 males and 10 females, with an age of (73.2 ± 16.1) years. On the basis of 2017 classification, the irreducible intertrochanteric fractures were classified into 2 types in the present 2021 classification. Type Ⅰ were interlocking fractures which were further classified into 3 subtypes: type ⅠA were sagittal interlocking ones (7 cases), type ⅠB greater trochanter interlocking ones (one case) and type ⅠC lesser trochanter interlocking ones (one case). Type Ⅱ were separating fractures which were further classified into 4 subtypes: type ⅡA were sagittal separating ones (4 cases), type ⅡB coronal separating ones (one case), type ⅡC rotational separating ones(one case) and type ⅡD complete separating ones (2 cases). All patients were treated by closed reduction and intramedullary nailing with different reduction strategies corresponding to their fracture types (application of ejector rods, clamps or prying techniques, etc.). A total of 132 patients with reducible femoral intertrochanteric fracture who had been admitted during the same period were selected as the control group. The fracture reduction time, intraoperative blood loss and Harris hip score at the last follow-up were compared between the 2 groups.Results:The 2 groups were comparable because there was no significant difference in their preoperative general data ( P>0.05). Type ⅠA accounted for the highest proportion of irreducible intertrochanteric fractures [41.3% (7/17)], followed by type ⅡA [23.6% (4/17)]. The fracture reduction time [(44.6 ± 6.7) min] in the irreducible group was significantly longer than that in the control group [(39.2 ± 9.6) min] ( P<0.05). There was no significant difference in intraoperative blood loss or Harris hip score at the last follow-up between the 2 groups ( P>0.05). Conclusions:Compared with the "2017 classification" , the "2021 classification" is more concise and easy to remember, and can directly prompt the corresponding proper fracture reduction techniques. The patients with irreducible intertrochanteric fracture using proper reduction techniques can obtain functional recovery similar to that in the patients with reducible intertrochanteric fracture after reduction and fixation.
4.Human acellular nerve allograft in repair of traumatic nerve defect of upper extremity: A preliminary observation
Bo ZHANG ; Ketong GONG ; Jianbing ZHANG ; Dake ZHU
Chinese Journal of Microsurgery 2022;45(2):139-143
Objective:To observe clinical outcomes of the repair of traumatic nerve defects in the proximal upper extremities by human acellular nerve allograft(hANG).Methods:Nerve defects in the upper extremities in 8 patients were repaired by hANG from March 2017 to January 2019. The patients were 6 males and 2 females with mean age of 35.4 (21-53) years old. The nerve defects were 2 radial nerve in distal upper arm, 4 median nerve in forearm, 1 interosseous dorsal nerve and 1 ulnar nerve in forearm. All injuries were acute nerve injury. Two patients had combined injury of upper arm muscle, 4 of forearm muscle and 1 of brachial artery defect. All wound were moderate to severe contaminated. The length of nerve defects was 30-60 (mean 45) mm. The surgical procedures were fixation of fracture, repair of the muscle and discovery of the broken ends of nerve and to repair with hANG. The postoperative follow-up period ranged 18 to 40 (mean 30.6) months to observe the local response of recovery. The efficacy was evaluated by the Upper Extremity Function Evaluation Standard set up by Hand Surgery Branch of Chinese Medical Association and Grading Standard of Muscle Strength.Results:No graft rejection was observed in all cases. Primarily healing was in 5 patients. Delayed healing in 2 patients and free skin grafting was performed. Local flap transfer was performed to repair the wound in 1 patient who developed a skin necrosis 10 days after surgery. Two patients with median nerve defects had nerve function restored well. The strength of finger grip and thumb opposition muscle restored to grade IV and the sensory function had restored S 3+. The interosseous dorsal nerve in 1 patient restored well. The strength of extensor digitorum tendon had restored to grade IV. Based on the evaluation criteria for the upper extremity issued by the Hand Surgery of the Chinese Medical Association, 3 patients was rated in excellent for function recovery, 1 in fair and 4 in poor. Conclusion:After throughout debridement, hANG can be applied in the repair of traumatic nerve defect in the proximal upper extremity in an emergency surgery and it can partially restore the nerve function.
5.Common Postzygotic Mutational Signatures in Healthy Adult Tissues Related to Embryonic Hypoxia
Hong YAQIANG ; Zhang DAKE ; Zhou XIANGTIAN ; Chen AILI ; Abliz AMIR ; Bai JIAN ; Wang LIANG ; Hu QINGTAO ; Gong KENAN ; Guan XIAONAN ; Liu MENGFEI ; Zheng XINCHANG ; Lai SHUJUAN ; Qu HONGZHU ; Zhao FUXIN ; Hao SHUANG ; Wu ZHEN ; Cai HONG ; Hu SHAOYAN ; Ma YUE ; Zhang JUNTING ; Ke YANG ; Wang QIAN-FEI ; Chen WEI ; Zeng CHANGQING
Genomics, Proteomics & Bioinformatics 2022;20(1):177-191
Postzygotic mutations are acquired in normal tissues throughout an individual's lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clock-like mutational processes,and the polymorphisms of epigenetic regulation genes influence the pro-portion of signature B in mutation profiles.Notably,signature C,characterized by C>T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6%of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C>T transitions at GpCpN sites;and indi-viduals'genetic background may also influence their postzygotic mutation profiles.
6.Repair of nail bed defect
Yanxin GAO ; Ketong GONG ; Dake ZHU ; Jie ZHANG
Chinese Journal of Microsurgery 2020;43(3):311-312,C3-1,C3-2,C3-3
The nail and nail bed are indispensibal structures with important function and esthetics role on the tip of fingers. Injury of the nail and nail bed often seriously affect the appearance and function of the fingers. The correct and timely treatment is essential for the restortation of good function according to the typing and degreement of the injuries. This paper reviewed about the function of nail and nail bed, typing of injury, evaluation of therapeutic effect and reconstruction of nail bed injury.
7.Lateral decubitus intramedullary nailing for femoral subtrochanteric fractures
Dake TONG ; Qiang WEI ; Peizhao LIU ; Xuzhou DUAN ; Qianyun HE ; Kang LIU ; Sheng QIN ; Kaihang XU ; Xuelin WU ; Hao ZHANG ; Hao TANG ; Dilshat ; Fang JI
Chinese Journal of Orthopaedic Trauma 2018;20(7):634-638
Objective To investigate the efficacy of lateral decubitus intramedullary nailing for treatment of subtrochanteric fractures of the femur.Methods From January 2012 to December 2015,23 patients with simple femoral subtrochanteric fracture were treated at Department of Orthopedic Trauma,Changhai Hospital.They were 15 males and 8 females,aged from 19 to 77 years (average,48.3 years).According to the Seinsheimer classification,there were 6 cases of type ⅡB,8 cases of type ⅡC,6 cases of type Ⅲ A,and 3 cases of type ⅢB.Their injuries were caused by traffic accident in 10 cases,falling from a height in 5 cases,and sprain in 8 cases.All patients were treated by closed reduction and anterograde intrarnedullary nailing at lateral decubitus.Their operative time,bleeding volume,fluoroscopic frequency,fracture healing time,functional recovery and complications were recorded and analyzed.Results Their operative time ranged from 55 to 80 min,averaging 65.7 min;their bleeding volumes ranged from 240 to 420 mL,averaging 304.3 mL;their fluoroscopic frequency ranged from 30 to 60 times,averaging 42.7 times.This cohort was followed up for 12 to 28 months (average,17.9 months).Their fracture healing time ranged from 4 to 10 months,averaging 5.5 months.Nonunion occurred in one patient but was cured by secondary operation.The HSS evaluation at the final follow-ups showed 17 excellent cases and 6 good ones,yielding an excellent to good rate of 100%.All the wounds healed by the first intention.No infection,deep vein thrombosis or implant failure was observed.Conclusion As lateral decubitus intramedullary nailing can achieve satisfactory clinical efficacy for subtrochanteric fractures of the femur,the body position of lateral decubitus may be a good alternative.
8.Clinical classification and strategies for irreducible femur intertrochanteric fractures
Dake TONG ; Wenbin DING ; Guangchao WANG ; Kang LIU ; Chen DING ; Qianyun HE ; Hao ZHANG ; Hao TANG ; Fang JI
Chinese Journal of Orthopaedic Trauma 2017;19(2):109-114
Objective To explore clinical classification and strategies for irreducible femur intertrochateric fractures.Methods A retrospective study was conducted of the 96 patients with irreducible intertrochanteric fracture who had been treated from January 2012 through December 2014 at our department.They were 47 men and 49 women,aged from 48 to 97 years (average,78.5 years).We classified the fractures according to location of fracture line and mechanism of fracture displacement into 5 types:13 cases of type Ⅰ (sagittal irreducible fracture),7 cases of type Ⅱ] (coronal irreducible fracture),72 cases of type Ⅲll (sagittal plus coronal irreducible fracture),zero of type Ⅳ (irreducible fracture involving the lesser trochanter),and 4 cases of type Ⅴ (irreducible fracture involving the greater trochanter).All the patients were managed using different techniques for closed reduction and fixation with proximal femoral nails antirotation Ⅱ.Results Of this series,limited open reduction was eventually conducted in 7.The operation time averaged 40 min;the amount of intraoperative blood loss averaged 200 mL.Fracture reduction was rated as grade Ⅰ in 78 cases and as grade Ⅱ in 18.The follow-up time averaged 16.6 months (from 12 to 24 months).All the fractures got united after an average of 5.8 months (from 3 to 9 months).The function of the affected hip was rated at the final follow-up using Harris scoring system as excellent in 79 cases and as good in 17,with an excellent to good rate of 100%.Refracture happened in one patient due to striking injury,urinary infection occurred in 2 patients and no wound infection was observed.Conclusion According to the classification and reduction strategy proposed by us,satisfactory reduction and fracture fixation can be achieved in management of irreducible intertrochanteric fractures.
9.Effect of human leukocyte antigen B*1502 genotype and age on serum homocysteine levels in children with seizures or epilepsy
Chun ZHANG ; Dake HE ; Xiaohui HUANG ; Xin WEI ; Jing MA ; Jia QI ; Yan LIU ; Ajing XU ; Shuhong BO
Journal of Clinical Pediatrics 2017;35(3):187-190
Objective To explore the effect of human leukocyte antigen B* genotype and age on serum homocysteine (Hcy) levels in children with seizures or epilepsy. Methods Fifteen children with seizures or epilepsy in whom HLA-B*15:02 genotype was detected during October 2015 to June 2016 were included. The plasma Hcy concentration in children with different genotypes was compared. The association of Hcy concentration and age was performed by linear-regression analysis. Results The mean concentration of Hcy was 8.38±4.23 μmol/L in children not carrying HLA-B*15:02 gene, which was obviously higher than that in children carrying HLA-B*15:02 gene 13.03±0.97 μmol/L (P<0.05). The Hcy concentration increased with the age (r2 =0.29, P<0.05). Conclusions Elder children with seizures or epilepsy carrying HLA-B*15:02 gene tend to have higher Hcy concentration and increased potential risk of disease. HLA-B*15:02 gene type and age can predict the changes of Hcy concentration in children with convulsions.
10.Effects of No.1 Weiyan Decoction on hypoxia and hypoxic tolerance in gastric mucosal epithelial cells in rats with gastric precancerous lesion
Chengzhe ZHANG ; Juncheng ZHUO ; Tiantian CAI ; Ziming ZHAO ; Huafeng PAN ; Yuxing CHEN ; Xiaohui ZENG ; Xuejun HUANG ; Nan YAO ; Dake CAI
Chinese Traditional Patent Medicine 2017;39(5):896-901
AIM To study the effects of No.1 Weiyan Decoction (Codonopsis Radix,Paeoniae Radix alba,Taraxaci Herba,etc.) on hypoxia and hypoxic tolerance in gastric mucosal epithelial cells in rats with precancerous lesion of gastric cancer (PLGC).METHODS Forty rats were randomly divided into normal,model,Vitacoenzyme Tablets and No.1 Weiyan Decoction groups.Except for the normal group,the rats in the other groups were given with N-methyl-N'-nitro-N-nitrosoguanidine and Little Chengqi Decoction to establish a PLGC rat model.Ten weeks after the administration,the gastric mucosal epithelial microvascular ultrastructure was observed,the expressions of Hif1a mRNA,HIF-1 α protein and VEGF protein in gastric mucosal epithelium were detected.RESULTS Compared with the normal group,the number of microvasculatures in gastric mucosal epithelium was decreased;lumen was severely stenosed or expansive;inner wall was not smooth and had adhesion;vascular endothelial cells were swollen;the expression of Hif1α mRNA showed an increasing trend;the expressions of HIF-1α protein and VEGF protein were anomalous in the model group.Compared with the model group,the gastric mucosal vascular lesion of PLGC rats was improved,and the expressions of Hif1a mRNA,HIF-1α protein and VEGF protein were significantly decreased in the No.1 Weiyan Decoction group.CONCLUSION No.1 Weiyan Decoction can improve hypoxia and hypoxia tolerance,and induce angiogenesis in gastric mucosal epithelium in PLGC rats.


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