1.A real-world retrospective study of pelvic floor muscle training efficacy using an APP-based home device
Ji-Qiong ZHENG ; Shi-Ping ZHOU ; Zhong-Yun ZHANG ; Wei-Qing QIAN ; Zheng-Wang ZHANG
Fudan University Journal of Medical Sciences 2024;51(1):96-101
Objective To retrospectively investigate the efficacy of pelvic floor muscle training(PFMT)using APP-based home device in the real-world scenario.Methods A retrospective survey was conducted among 171 000 Chinese female users over 18 years old who freely registered APP and performed PFMT using a domestic manufactured home device from Oct 1,2019 to Mar 31,2021.The Patient Global Impression of Improvement(PGI-I)questionnaires concerning pelvic floor general condition,sexual satisfaction and other three major symptoms related to pelvic floor muscle laxity such as stress urinary incontinence(SUI),pelvic organ prolapse(POP),and vaginal laxity(VL)were broadcast public online for users to self-assess the improvement.The vaginal muscle strength values prior and post training recorded by APP were also reported.All data were collected anonymously for further stratified analysis.Results A total of 984 valid questionnaires were collected by systematic sampling.The PGI-I scores of pelvic floor general condition(P=0.000 1),sexual satisfaction(P=0.009),SUI(P=0.000 1),POP(P=0.044)and VL(P=0.034)were statistically significant in users who reported to use the device for 3 months or more compared with those less than 3 months.In addition,the increase of vaginal muscle strength was related to the improvement of PGI-I scores in SUI and POP with statistical significance.There were no significant difference in subgroups such as age,education,parity,and delivery mode.Conclusion The subjective benefit of pelvic floor function-related symptoms and the improvement of vaginal muscle strength could be observed after PFMT for three months or more using APP-based home device in Chinese women in the real-world scenario.
2.Clinical trial of brexpiprazole in the treatment of adults with acute schizophrenia
Shu-Zhe ZHOU ; Liang LI ; Dong YANG ; Jin-Guo ZHAI ; Tao JIANG ; Yu-Zhong SHI ; Bin WU ; Xiang-Ping WU ; Ke-Qing LI ; Tie-Bang LIU ; Jie LI ; Shi-You TANG ; Li-Li WANG ; Xue-Yi WANG ; Yun-Long TAN ; Qi LIU ; Uki MOTOMICHI ; Ming-Ji XIAN ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(5):654-658
Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50%(140 cases/184 cases)and 82.40%(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P>0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P>0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P>0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00%vs.64.50%,P>0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.
3.Analysis of the causes of cage subsidence after oblique lateral lumbar interbody fusion
Zhong-You ZENG ; Ping-Quan CHEN ; Xing ZHAO ; Hong-Fei WU ; Jian-Qiao ZHANG ; Xiang-Qian FANG ; Yong-Xing SONG ; Wei YU ; Fei PEI ; Shun-Wu FAN ; Guo-Hao SONG ; Shi-Yang FAN
China Journal of Orthopaedics and Traumatology 2024;37(1):33-44
Objective To observe the cage subsidence after oblique lateral interbody fusion(OLIF)for lumbar spondylo-sis,summarize the characteristics of the cage subsidence,analyze causes,and propose preventive measures.Methods The data of 144 patients of lumbar spine lesions admitted to our hospital from October 2015 to December 2018 were retrospectively ana-lyzed.There were 43 males and 101 females,and the age ranged from 20 to 81 years old,with an average of(60.90±10.06)years old.Disease types:17 patients of lumbar intervertebral disc degenerative disease,12 patients of giant lumbar disc hernia-tion,5 patients of discogenic low back pain,33 patients of lumbar spinal stenosis,26 patients of lumbar degenerative spondy-lolisthesis,28 patients of lumbar spondylolisthesis with spondylolisthesis,11 patients of adjacent vertebral disease after lumbar internal fixation,7 patients of primary spondylitis in the inflammatory outcome stage,and 5 patients of lumbar degenerative scoliosis.Preoperative dual-energy X-ray bone mineral density examination showed 57 patients of osteopenia or osteoporosis,and 87 patients of normal bone density.The number of fusion segments:124 patients of single-segment,11 patients of two-seg-ment,8 patients of three-segment,four-segment 1 patient.There were 40 patients treated by stand-alone OLIF,and 104 patients by OLIF combined with posterior pedicle screw.Observed the occurrence of fusion cage settlement after operation,conducted monofactor analysis on possible risk factors,and observed the influence of fusion cage settlement on clinical results.Results All operations were successfully completed,the median operation time was 99 min,and the median intraoperative blood loss was 106 ml.Intraoperative endplate injury occurred in 30 patients and vertebral fracture occurred in 5 patients.The mean follow-up was(14.57±7.14)months from 6 to 30 months.During the follow-up,except for the patients of primary lumbar interstitial in-flammation and some patients of lumbar spondylolisthesis with spondylolisthesis,the others all had different degrees of cage subsidence.Cage subsidence classification:119 patients were normal subsidence,and 25 patients were abnormal subsidence(23 patients were grade Ⅰ,and 2 patients were grade Ⅱ).There was no loosening or rupture of the pedicle screw system.The height of the intervertebral space recovered from the preoperative average(9.48±1.84)mm to the postoperative average(12.65±2.03)mm,and the average(10.51±1.81)mm at the last follow-up.There were statistical differences between postop-erative and preoperative,and between the last follow-up and postoperative.The interbody fusion rate was 94.4%.The low back pain VAS decreased from the preoperative average(6.55±2.2 9)to the last follow-up(1.40±0.82),and there was statistically significant different.The leg pain VAS decreased from the preoperative average(4.72±1.49)to the final follow-up(0.60± 0.03),and the difference was statistically significant(t=9.13,P<0.000 1).The ODI index recovered from the preoperative av-erage(38.50±6.98)%to the latest follow-up(11.30±3.27)%,and there was statistically significant different.The complication rate was 31.3%(45/144),and the reoperation rate was 9.72%(14/144).Among them,8 patients were reoperated due to fusion cage subsidence or displacement,accounting for 57.14%(8/14)of reoperation.The fusion cage subsidence in this group had obvious characteristics.The monofactor analysis showed that the number of abnormal subsidence patients in the osteopenia or osteoporosis group,Stand-alone OLIF group,2 or more segments fusion group,and endplate injury group was higher than that in the normal bone mass group,OLIF combined with pedicle screw fixation group,single segment fusion group,and no endplate injury group,and the comparison had statistical differences.Conclusion Cage subsidence is a common phenomenon after 0-LIF surgery.Preoperative osteopenia or osteoporosis,Stand-alone OLIF,2 or more segments of fusion and intraoperative end-plate injury may be important factors for postoperative fusion cage subsidence.Although there is no significant correlation be-tween the degree of cage subsidence and clinical symptoms,there is a risk of cage migration,and prevention needs to be strengthened to reduce serious complications caused by fusion of cage subsidence,including reoperation.
4.MRI diagnosis of spinal epidural lipomatosis in high-altitude areas
Lijuan ZHOU ; Yongcang WEN ; Gensheng ZHANG ; Wei SHI ; Youyang XIE ; Quancheng ZHANG ; Jingsong ZHONG ; Wei CHU
Chinese Journal of Radiological Health 2024;33(4):435-439
Objective To analyze the magnetic resonance images (MRI) of patients with spinal epidural lipomatosis (SEL) in high-altitude areas and to determine the optimal cut-off value for diagnosis with epidural fat thickness. Methods This retrospective study included patients who underwent lumbosacral MRI examination for lumbosacral pain in Ping’an District Hospital of Traditional Chinese Medicine, Haidong City, China from January 1, 2021 to December 31, 2022. The epidural fat thickness in vertebral segments T12/L1 to L5/S1 was compared between the SEL group and the non-SEL group. The diagnostic efficacy with different cut-off values at each vertebral segment was evaluated. Between-group comparisons were performed using the t-test, Mann-Whitney U test, chi-square test, or modified chi-square test. The area under the receiver operating characteristic (AUC) was used to evaluate the diagnostic efficiency. The DeLong test was used to compare AUC between the two groups. Results A total of 370 patients were included (60 in the SEL group and 310 in the non-SEL group). There were no significant differences in age, sex, height, body weight, and body mass index between the two groups (all P > 0.05). At different vertebral segments, the epidural fat thickness was significantly higher in the SEL group than in the non-SEL group (all P < 0.05). The cut-off values for SEL diagnosis with epidural fat thickness in segments T12/L1 to L5/S1 were 2.23, 4.25, 4.85, 5.57, 7.21, and 8 mm, respectively. The AUC of MRI SEL diagnosis with epidural fat thickness in segment L5/S1 was the highest (0.945, 95% confidence interval [CI]: 0.916-0.966, P < 0.001). SEL diagnosis with epidural fat thickness > 8 mm in segment L5/S1 was the most accurate, with an AUC of 0.931 (95% CI: 0.901-0.955, P < 0.001), a sensitivity of 95.0%, and a specificity of 91.3%; this AUC was significantly higher than those of diagnosis with other cut-off values (all P < 0.05). Conclusion SEL patients have significantly increased epidural fat in the spinal canal. Epidural fat thickness > 8 mm in segment L5/S1 can be used for diagnosis of SEL with improved efficiency and accuracy.
5.Grade quality standard development of Lycium barbarum fruits from Ningxia genuine producing area
Zhong-lian YU ; Xue-ping LI ; Li YANG ; Zheng-tao WANG ; Wen-jing LIU ; Rui WANG ; Yan-hong SHI
Acta Pharmaceutica Sinica 2024;59(5):1399-1407
An integrated evaluation model based on the combination of traditional trait identification and modern chemical analysis was used for the identification of key indexes of grade classification and the establishment of grade quality standard of
6.Trend of gastrointestinal and liver diseases in China: Results of the Global Burden of Disease Study, 2019
Xiaowei TANG ; Ping WANG ; Shu HUANG ; Jieyu PENG ; Wei ZHANG ; Xiaomin SHI ; Lei SHI ; Xiaolin ZHONG ; Muhan LYU ; Xian ZHOU ; Enqiang LINGHU
Chinese Medical Journal 2024;137(19):2358-2368
Background::China is one of the countries with the largest burden of gastrointestinal and liver diseases (GILD) in the world. The GILD constitutes various causes of mortality and disability. The study aimed to investigate the trend of GILD in China using the Global Burden of Diseases Study 2019 (GBD 2019) data resources from 1990 to 2019.Methods::The data on the age-standardized mortality rates (ASMR) and disability-adjusted life years (DALYs) for GILD in China from 1990 to 2019 were collected from the GBD 2019 data resources. Furthermore, the ranking of the main causes of deaths and DALYs, as well as the trends of ASMR, DALYs, years of life lost (YLLs), and years of life lost due to disability (YLDs) per 1,000,000 in GILD were reported.Results::The ASMR and DALYs for stomach cancer, liver cancer, and esophageal cancer, which ranked top three among the GILDs from 1990 to 2019, were gradually decreasing. Significant decreases in the ASMR and DALYs were found in diarrheal diseases and acute hepatitis (A, E, and C). However, noteworthy increases were found in those of colon and rectum cancer (CRC) and pancreatic cancer. Trend of DALYs, mortality, and YLLs rates for most of GILD were decreasing from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trend. The DALYs, mortality and YLLs of most GILD diseases showed decreasing trends from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trends.Conclusions::The result of the GBD 2019 showed that the rates of most GILDs decreased in China; however, gastrointestinal and liver cancer, such as stomach cancer still held the top ranking. Furthermore, the shift from infectious diseases to non-communicable causes among GILD burden is occurring.
7.A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020
Cai-Yun WANG ; Hong-Mei XU ; Gang LIU ; Jing LIU ; Hui YU ; Bi-Quan CHEN ; Guo ZHENG ; Min SHU ; Li-Jun DU ; Zhi-Wei XU ; Li-Su HUANG ; Hai-Bo LI ; Dong WANG ; Song-Ting BAI ; Qing-Wen SHAN ; Chun-Hui ZHU ; Jian-Mei TIAN ; Jian-Hua HAO ; Ai-Wei LIN ; Dao-Jiong LIN ; Jin-Zhun WU ; Xin-Hua ZHANG ; Qing CAO ; Zhong-Bin TAO ; Yuan CHEN ; Guo-Long ZHU ; Ping XUE ; Zheng-Zhen TANG ; Xue-Wen SU ; Zheng-Hai QU ; Shi-Yong ZHAO ; Lin PANG ; Hui-Ling DENG ; Sai-Nan SHU ; Ying-Hu CHEN
Chinese Journal of Contemporary Pediatrics 2024;26(2):131-138
Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]
8.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
9.Reasons and strategies of reoperation after oblique lateral interbody fusion
Zhong-You ZENG ; Deng-Wei HE ; Wen-Fei NI ; Ping-Quan CHEN ; Wei YU ; Yong-Xing SONG ; Hong-Fei WU ; Shi-Yang FAN ; Guo-Hao SONG ; Hai-Feng WANG ; Fei PEI
China Journal of Orthopaedics and Traumatology 2024;37(8):756-764
Objective To summarize the reasons and management strategies of reoperation after oblique lateral interbody fusion(OLIF),and put forward preventive measures.Methods From October 2015 to December 2019,23 patients who under-went reoperation after OLIF in four spine surgery centers were retrospectively analyzed.There were 9 males and 14 females with an average age of(61.89±8.80)years old ranging from 44 to 81 years old.The index diagnosis was degenerative lumbar intervertebral dics diseases in 3 cases,discogenie low back pain in 1 case,degenerative lumbar spondylolisthesis in 6 cases,lumbar spinal stenosis in 9 cases and degenerative lumbar spinal kyphoscoliosis in 4 cases.Sixteen patients were primarily treated with Stand-alone OLIF procedures and 7 cases were primarily treated with OLIF combined with posterior pedicle screw fixation.There were 17 cases of single fusion segment,2 of 2 fusion segments,4 of 3 fusion segments.All the cases underwent reoperation within 3 months after the initial surgery.The strategies of reoperation included supplementary posterior pedicle screw instrumentation in 16 cases;posterior laminectomy,cage adjustment and neurolysis in 2 cases,arthroplasty and neuroly-sis under endoscope in 1 case,posterior laminectomy and neurolysis in 1 case,pedicle screw adjustment in 1 case,exploration and decompression under percutaneous endoscopic in 1 case,interbody fusion cage and pedicle screw revision in 1 case.Visu-al analogue scale(VAS)and Oswestry disability index(ODI)index were used to evaluate and compare the recovery of low back pain and lumbar function before reoperation and at the last follow-up.During the follow-up process,the phenomenon of fusion cage settlement or re-displacement,as well as the condition of intervertebral fusion,were observed.The changes in in-tervertebral space height before the first operation,after the first operation,before the second operation,3 to 5 days after the second operation,6 months after the second operation,and at the latest follow-up were measured and compared.Results There was no skin necrosis and infection.All patients were followed up from 12 to 48 months with an average of(28.1±7.3)months.Nerve root injury symptoms were relieved within 3 to 6 months.No cage transverse shifting and no dislodgement,loosening or breakage of the instrumentation was observed in any patient during the follow-up period.Though the intervertebral disc height was obviously increased at the first postoperative,there was a rapid loss in the early stage,and still partially lost after reopera-tion.The VAS for back pain recovered from(6.20±1.69)points preoperatively to(1.60±0.71)points postoperatively(P<0.05).The ODI recovered from(40.60±7.01)%preoperatively to(9.14±2.66)%postoperatively(P<0.05).Conclusion There is a risk of reoperation due to failure after OLIF surgery.The reasons for reoperation include preoperative bone loss or osteoporosis the initial surgery was performed by Stand-alone,intraoperative endplate injury,significant subsidence of the fusion cage after surgery,postoperative fusion cage displacement,nerve damage,etc.As long as it is discovered in a timely manner and handled properly,further surgery after OLIF surgery can achieve better clinical results,but prevention still needs to be strengthened.
10.A Novel Trifluoromethyl Quinazoline Compound Inhibits Drug-resistant Glioblastoma Cells Proliferation
Xiao-Zhong CHEN ; Shi-Nan WEI ; Heng LUO ; Peng ZHANG ; Ping SUN ; Bao-Fei SUN
Chinese Journal of Biochemistry and Molecular Biology 2024;40(9):1250-1261
The current treatment of glioma is facing drug resistance,which limits the efficacy of traditional chemotherapy drugs.This study aims to explore the potential mechanisms of the trifluoromethylquinazoline compound(KZL204)against glioma.Through the Cell Counting Kit-8(CCK-8)assay,we found that KZL204 significantly inhibits the growth of drug-resistant cancer cells,with a 48-hour half-maximal inhibitory concentration(IC50)of 3.63±0.38 μmol/L,which is significantly better than the positive control drug temozolomide(TMZ)(IC50 value of 81.67±5.49 μmol/L).Additionally,flow cytometry analysis showed that KZL204 treatment significantly increased the apoptosis rate of drug-resistant tumor cells and arrested the cell cycle at the G2/M phase.At the same time,the Transwell assay confirmed the inhibitory effect of KZL204 on the migration and invasion of drug-resistant cancer cells.Transcriptome analysis revealed 2 435 differentially expressed genes in drug-resistant cancer cells treated with KZL204,of which 1 320 were upregulated,and 1 115 were downregulated.KEGG and GO enrichment analysis showed that these differential genes were significantly enriched in apoptosis-related signaling pathways.Further bioinformatics prediction and Venn diagram analysis identified 35 potential core targets,with the PI3K-AKT signaling pathway being the most significant among the differentially expressed genes.Quantitative real-time PCR(RT-qPCR)experiments confirmed the downregulating effects of KZL204 on genes such as CREB3L1,CSF1,CXCL5,BCL3,and the upregulating effects on genes like FOS,LT A,PTGS2,MAP2K3.Immunoblotting experiments at the protein level also confirmed the impact of KZL204 on the expression of apoptotic proteins,including the upregulation of Bax,cleaved Caspase-3 protein,and the downregulation ofAKT,Bcl-2,Caspase-3,and Caspase-8 protein expression.In summary,KZL204 significantly inhibits the growth and metastasis of drug-resistant glioblastoma and induces apoptosis and cell cycle arrest by regulating the PI3K-AKT and apoptosis-related signaling pathways,demonstrating its potential as a candidate drug against drug-resistant glioma.

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