2.CDK5-triggered G6PD phosphorylation at threonine 91 facilitating redox homeostasis reveals a vulnerability in breast cancer.
Yuncheng BEI ; Sijie WANG ; Rui WANG ; Owais AHMAD ; Meng JIA ; Pengju YAO ; Jianguo JI ; Pingping SHEN
Acta Pharmaceutica Sinica B 2025;15(3):1608-1625
Glucose-6-phosphate dehydrogenase (G6PD), the first rate-limiting enzyme of the pentose phosphate pathway (PPP), is aberrantly activated in multiple types of human cancers, governing the progression of tumor cells as well as the efficacy of anticancer therapy. Here, we discovered that cyclin-dependent kinase 5 (CDK5) rewired glucose metabolism from glycolysis to PPP in breast cancer (BC) cells by activating G6PD to keep intracellular redox homeostasis under oxidative stress. Mechanistically, CDK5-phosphorylated G6PD at Thr-91 facilitated the assembly of inactive monomers of G6PD into active dimers. More importantly, CDK5-induced pho-G6PD was explicitly observed specifically in tumor tissues in human BC specimens. Pharmacological inhibition of CDK5 remarkably abrogated G6PD phosphorylation, attenuated tumor growth and metastasis, and synergistically sensitized BC cells to poly-ADP-ribose polymerase (PARP) inhibitor Olaparib, in xenograft mouse models. Collectively, our results establish the crucial role of CDK5-mediated phosphorylation of G6PD in BC growth and metastasis and provide a therapeutic regimen for BC treatment.
3.The effects rehabilitation timing on the motor functioning of children with a traumatic brain injury
Zerui ZHENG ; Qin FU ; Min ZHOU ; Jianguo CAO ; Linjuan WANG ; Fanling MENG
Chinese Journal of Physical Medicine and Rehabilitation 2024;46(11):983-987
Objective:To document any impact of the timing of rehabilitation interventions on the recovery of motor function among children after a traumatic brain injury (TBI).Methods:Seventy-one children with a TBI were randomly divided into a control group ( n=36) and an observation group ( n=35). All received comprehensive rehabilitation-15 to 30 days after admission for those in the control group and 2 to 14 days after admission for the observation group. It included joint range-of-motion training, multi-sensory stimulation training, low-frequency electrical stimulation, and acupuncture. Before the experiment and 4, 12 and 24 weeks afterward, everyone′s motor functioning, muscle tone, and functional independence were quantified using the Fugl-Meyer Assessment (FMA), the Modified Ashworth Scale (MAS), and the WeeFIM pediatric functional independence measure. Results:Four weeks after the intervention the average FMA and WeeFIM scores of both groups had already increased significantly. At 12 and 24 weeks the average FMA and WeeFIM scores of the observation group were significantly higher than the control group′s averages. Muscle tone was then also significantly better on average. There was no significant difference in the incidence of rehabilitation interruptions between the two groups.Conclusion:Early comprehensive rehabilitation intervention within 2 to 14 days of admission can effectively better the motor functioning and functional independence of pediatric TBI patients.
4.Association of SLC6A4 gene c.*670T>G polymorphism with the risk for asthma and peripheral blood cytological characteristics among ethnic Zhuang Chinese population.
Gao CHEN ; Jianguo XU ; Shuai WEI ; Minlv MENG ; Chen LAN ; Chunru ZHAO ; Yingjiao MA
Chinese Journal of Medical Genetics 2023;40(10):1228-1235
OBJECTIVE:
To assess the association of SLC6A4 gene c.*670T>G polymorphism with the risk for asthma and peripheral blood cytological characteristics among ethnic Zhuang Chinese from Guangxi, China.
METHODS:
From May 2017 to March 2020, 258 patients diagnosed with asthma and 244 healthy controls were recruited from the Affiliated Hospital of Youjiang Minzhu Medical College and the People's Hospital of Hechi. Genotypes of the c.*670T>G polymorphism were determined by Sanger sequencing. Flow cytometry was used in combination with an electrical impedance method for the counting and classification of peripheral blood cells.
RESULTS:
Compared with the T allele, the G allele of the c.*670T>G polymorphism was associated with the risk for asthma in the population (OR = 1.54, 95%CI = 1.15-2.06; P = 0.004). Compared with the GT and TT genotypes, homozygous GG genotype also comprised a risk factor (OR = 1.66, 95%CI = 1.16-2.38; P = 0.005). Stratification of the risk factors showed that the homozygous GG genotype has increased the risk of asthma in males and urban residents (P < 0.01). The erythrocyte, hemoglobin and platelet counts of the asthma group were significantly higher than the control group (P < 0.001). The GG, GT and TT genotypes have respectively accounted for 82.35%, 17.65% and 0% of the samples with platelets exceeding the normal value. The overall platelet level of GG genotype was higher than GT+TT genotype (P < 0.05). The significant association was verified by the false positive report probability, and at a prior probability level of 0.1, G vs. T false positive probability was 0.071, and GG vs. GT+TT false positive probability was 0.153.
CONCLUSION
The GG genotype of the c.*670T>G polymorphism is associated with the risk for asthma among ethnic Zhuang Chinese from northwest Guangxi. Above finding has also enriched the genotypic data and peripheral blood phenotype for this polymorphism.
Male
;
Humans
;
East Asian People
;
China
;
Genotype
;
Alleles
;
Asthma/genetics*
;
Serotonin Plasma Membrane Transport Proteins
5.Current status of surgery for portal hypertension in China: a national multi-center survey analysis
Lei ZHENG ; Haiyang LI ; Jizhou WANG ; Xiao LIANG ; Jian DOU ; Jitao WANG ; Qiang FAN ; Xiong DING ; Wenlong ZHAI ; Yun JIN ; Bo LI ; Songqing HE ; Tao LI ; Jun LIU ; Kui WANG ; Zhiwei LI ; Yongyi ZENG ; Yingmei SHAO ; Yang BU ; Dong SHANG ; Yong MA ; Cheng LOU ; Xinmin YIN ; Jiefeng HE ; Haihong ZHU ; Jincai WU ; Zhidan XU ; Dunzhu BASANG ; Jianguo LU ; Liting ZHANG ; Jianguo ZHAO ; Ling LYU ; Guoyue LYU ; Nim CHOI ; To Tan CHEUNG ; Meng LUO ; Wanguang ZHANG ; Xiaolong QI ; Xiaoping CHEN
Chinese Journal of Organ Transplantation 2023;44(3):152-159
Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.
6.Evidence-based guidelines for food allergy of children in China
Wei ZHOU ; Jing ZHAO ; Huilian CHE ; Jianguo HONG ; Li HONG ; Hong LI ; Zailing LI ; Juan MENG ; Li SHA ; Jie SHAO ; Kunling SHEN ; Lianglu WANG ; Li XIANG ; Huan XING ; Sainan BIAN ; Nannan JIANG ; Hong JING ; Ling LIU ; Pengxiang ZHOU ; Weiwei ZHU
Chinese Journal of Applied Clinical Pediatrics 2022;37(8):572-583
The diagnosis of food allergy in children is one hotspot attracting people′s attention in recent years.The incidence of it shows an increasing trend which exposes problems in the understanding of children′s food allergy in China, especially in the misdiagnosis and missed diagnosis.To further standardize the diagnosis and treatment of food allergy in children, based on the current domestic, foreign guidelines and relevant research evidence, the guideline recommends 16 clinical hot-button issues in the 4 aspects of diagnosis, treatment, prognosis, and prevention.Finally, a diagnosis flowchart has been formulated.The guideline aims to improve the standard diagnosis and treatment of food allergies in children in China.
7.Urodynamic study of bladder dysfunction after radical hysterectomy of cervical cancer
Jianjian WANG ; Yanping ZHANG ; Erpeng LIU ; Qingbo MENG ; Chunzi JIANG ; Xinghuan YANG ; Jianguo WEN
Chinese Journal of Geriatrics 2022;41(3):302-306
Objective:To explore the urodynamic characteristics of bladder function in patients with abnormal urination after radical hysterectomy of cervical cancer.Methods:In a prospective self-controlled study, a total of 84 patients with cervical cancer and clinical stage of ⅠB to ⅡA, meeting the preoperative inclusion criteria in our hospital from January 2016 to June 2018 were enrolled.All patients were tested for urodynamic testing 1 week before and 6 months after surgery.Patient bladder function status was observed and evaluated before and after surgery and urodynamic examination results were analyzed.Results:Of 84 study cases, the 58 patients developed abnormal urination after radical surgery, there were no urination abnormalities in 26 cases.There was no significant difference in age, clinical stage and pathological diagnosis between patients with and without urination abnormalities.Abnormal urination after radical surgery included difficulty in urinating(55%), frequent urination with a feeling of urination not complete(34%), stress urinary incontinence(7%), and urinary incontinence(4%). Among the 26 patients without urination abnormalities after radical surgery, only one case showed an abnormal urodynamic examination(abnormal bladder sensation). In patients without abnormal urination after surgery, differences in the urodynamic examination findings between pre-and post-surgery were not statistically significant(all P> 0.05). At the same time, in all cases of abnormal urination after radical hysterectomy of cervical cancer, 43 patients(74%)with bladder dysfunction had normal urination pattern before operation, but after operation, the urination abnormality required abdominal pressure.Of the patients with bladder dysfunction after surgery, the maximum flow rate(Qmax)was(12.9±10.3)ml/s, the average flow rate(Qave)was(6.0±4.2)ml/s, the voided volume was(148.0±36.8)ml, voiding time was(32.9±22.1)s, maximum flow time was(11.4±5.0)s, postvoid residual urine was(260.2±219.2)ml, maximal detrusor pressure was(12.1±8.9)cmH 2O, bladder compliance was(16.1±4.3)ml/cmH 2O, normal desire to void was(354.5±204.3)ml, maximal capacity was(587.4±152.5)ml, maximum urethral pressure was(97.6±33.1)cmH 2O, maximum urethral closure pressure was(89.9±36.4)cmH 2O, and function urethral length was(29.6±6.5)mm; In comparison, the above indexes-corresponding values at 1 week before surgery were respectively as follows: the Qmax was(25.1±11.4)ml/s, the Qave was(11.4±6.6)ml/s, the voided volume was(318.6±96.4)ml, voiding time was(29.2±18.5)s, maximum flow time was(6.7±3.9)s, postvoid residual urine was(29.9±21.5)ml, maximal detrusor pressure was(31.9±21.4)cmH 2O, bladder compliance was(78.1±33.9)ml/cmH 2O, normal desire to void was(258.2±185.5)ml, maximal capacity was(335.1±124.9)ml, maximum urethral pressure was(96.4±33.9)cm H 2O, maximum urethral closure pressure was(88.5±35.2)cmH 2O, and function urethral length was(37.2±7.2)mm.It can be seen that Qmax, Qave, voided volume, maximum detrusor pressure, bladder compliance, and functional urethral length in patients with abnormal urination are significantly lower after radical hysterectomy of cervical cancer than before the surgery.While, normal desire to void, maximum capacity, maximum flow time, and postvoid residual urine volume were higher after radical hysterectomy than before surgery( P<0.05). In addition, there was no significant difference in voiding time, maximum urethral pressure and maximum urethral closure pressure between pre-and post-operation.Besides, it is worth noting that there was no significant difference in preoperative urodynamic test results between patients without abnormal urination versus patients with abnormal urination( P>0.05), and the difference in urodynamic test results between the two groups is statistically significant( P<0.05). There was no statistically significant difference in abnormal urination and in urodynamic test results between different clinical stages and between different pathological types( P>0.05). Conclusions:The characteristics of urinary dynamics in patients with abnormal urination after radical hysterectomy of cervical cancer are mainly manifested as decreased bladder sensory function and abnormal detrusor function.And the urodynamic test can provide objective clinical indicators for early diagnosis.
8.Case report of intellectual developmental disorder with dysmorphic facies and behavioral abnormalities due to FBXO11 gene mutation
Ying REN ; Wandong HU ; Zaifen GAO ; Yao MENG ; Guifu GENG ; Ruifeng JIN ; Jianguo SHI ; Hongwei ZHANG
Chinese Journal of Applied Clinical Pediatrics 2022;37(18):1415-1417
A retrospective analysis was performed on the clinical data of a case of intellectual developmental disorders with dysmorphic facies and behavioral abnormalities admitted in the Department of Neurology and Endocrinology, Children′s Hospital Affiliated to Shandong University in February 2020.The proband was a 3 years and 6 months old boy, who was hospitalized because of " convulsions for more than 1 year" . Physical examination revealed facial deformities.Gesell developmental schedule showed that adaptive and gross motor behavior development was severely retarded, and fine motor, language and personal-social behavior development was moderately retarded.Brain magnetic resonance imaging suggested schizencephaly.Electroencephalogram results indicated extensive discharges mainly in bilateral anterior head areas, and one myoclonic seizure was detected.Gene detection results disclosed the pathogenic variation of the proband, which was a heterozygote mutation (c.2480_2484del) in FBXO11 gene.High-throughput sequencing technology increases the possibility of identifying potential genetic mutations as the cause of disease.Patients with recurrent seizures, multi-malformation and general developmental delays should undergo gene detection in time to clarify the etiology.This technique can guide prenatal diagnosis and genetic counseling.
9.Research advances of the prognostic value of onodera prognostic nutrition index for mali-gnant tumors of digestive systems
Xueyan CHEN ; Jianliang QIAO ; Jun LI ; Jianxiang NIU ; Jianguo ZHAO ; Sai HAN ; Xingkai MENG
Chinese Journal of Digestive Surgery 2022;21(10):1390-1394
Onodera prognostic nutrition index (OPNI) is a simple and effective parameter. It is calculated by serum albumin level and peripheral blood lymphocyte count. Initially, OPNI is used to assess preoperative nutritional status and surgical risk. In recent years, researchers have found that OPNI is related to the prognosis of many tumors. Simple and accurate prognosis evaluation can help to select treatment methods for digestive system malignant tumors, determine the best pre-operative treatment time and operation time, and improve the survival rate of patients with diges-tive system malignant tumors. The authors review the related literatures at home and abroad, and summarize the research advances in the prognostic value of OPNI for malignant tumors of digestive systems.
10.The analysis of urodynamic and clinical features of detrusor underactivity in elderly men
Yan ZHANG ; Ruili ZHANG ; Lingfeng MENG ; Yanping ZHANG ; Qingwei WANG ; Lianghua JIA ; Yaoguang ZHANG ; Qifeng DOU ; Jianguo WEN
Chinese Journal of Geriatrics 2021;40(7):886-889
Objective:To analyze the urodynamic and clinical features of detrusor underactivity(DU)in elderly men aged 60 years and over.Methods:Five hundred and seventy-three men aged 60 years and over underwent urodynamic measurements due to dysuria were retrospectively analyzed.According to the urodynamic parameters of bladder contractibility index(BCI)and bladder outlet obstruction index(BOOI), they were divided into the three groups: only detrusor underactivity(DU group)(BCI<100 and BOOI<20), only bladder outlet obstruction(BOO group)(BCI≥100 and BOOI≥40), and the combined non-DU and non-BOO group(NDB group)(BCI≥100 and BOOI<20). The urodynamic and clinical features were compared between the three groups.Results:The internalized 323 patients meeting inclusion and exclusion criteria were divided into 3 groups: 75 in the DU, 207 in the BOO and 41 in the NDB.The age was higher in DU and BOO groups than in NDB group( P<0.05). The DU group versus the NDB group showed the higher levels or values in the volume at first desire(FDV)[(279±80)ml vs.(238±72)ml], the proportions of incomplete bladder emptying(41% vs.17%), urine flow interruption(39% vs.15%)and retention(26% vs.7%), and the lower levels in the voiding efficiency(VE)[(61±32)% vs.(110±41)%], (all P<0.05). The DU group vs.the BOO group showed the increased levels or values in the FDV[(279±80)ml vs.(206±67)ml]and maximum cytometric capacity(MCC)(353±113 ml vs.281±94 ml)and the proportions of urine flow interruption(39% vs.22%), TURP(26% vs.6%), and retention(26% vs.14%), and the decreased levels or values in the VE[(61±32)% vs.(78±37%)], the proportions of DO(41% vs.77%), urgency(26% vs.43%)and nocturia(23% vs.39%)(all P<0.05). Conclusions:The main urodynamic and clinical features are manifested as the reduction of bladder sensation and bladder emptying rate, urine flow interruption, urinary retention and having a TURP history in elderly man with detrusor underactivity.The proportions of DU and BOO are increased along with aging.

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