1.Role of SWI/SNF Chromatin Remodeling Complex in Tumor Drug Resistance
Gui-Zhen ZHU ; Qiao YE ; Yuan LUO ; Jie PENG ; Lu WANG ; Zhao-Ting YANG ; Feng-Sen DUAN ; Bing-Qian GUO ; Zhu-Song MEI ; Guang-Yun WANG
Progress in Biochemistry and Biophysics 2025;52(1):20-31
Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca2+ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca2+ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.
2.Evaluation of the treatment effect on sinus elevation and implant restoration in cases with odontogenic maxillary sinusitis after tooth extraction
ZHU Yunying ; LIU Yun ; XU Ting ; LIU Zhenzhen ; CAO Shaoping ; WANG Zhangsong ; WU Donghui
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(3):202-208
Objective:
To investigate the clinical effects of sinus elevation surgery and implant restorationdue to insufficient bone massafter tooth extraction in patients with odontogenic maxillary sinusitis (OMS) and to provide a reference for use in clinical practice.
Methods:
This study was reviewed and approved by the Ethics Committee, and informed consent was obtained from the patients. Forty-five teeth were extracted from patients with OMS in the maxillary posterior area (the study group). Sinus elevation and implantation were performed due to insufficient bone height in the implant area 6-8 months after tooth extraction in the study group. Forty-eight teeth were extracted from patients without "OMS" in the maxillary posterior area (the control group), and sinus elevation and implantation were performed due to insufficient bone height in the implant area 6-8 months after tooth extraction inthe control group. In the study group, 13 cases of discontinuous maxillary sinus floor bone and residual alveolar bone height of the maxillary sinus floor less than 4 mm were addressed with lateral wall sinus elevation, and the other 32 cases were addressed with crest-approach sinus elevation. In the control group, 8 cases of residual alveolar bone height less than 4 mm in the maxillary sinus floor were addressed with lateral wall sinus,and the other 40 cases were addressed with crest approach sinus elevation. Restorations were placed 6 to 8 months after surgery. The patients were followed up 21 days, 3 months, and 8 months after implantation and every 6 months after the placement of the restorations. The sinus bone gain (SBG), apical bone height (ABL) and marginal bone loss (MBL) were statistically analyzed 24 months after the restoration.
Results:
The average preoperative mucosal thickness in the 45 patients in the study group was (1.556 ± 0.693) mm, which was significantly larger than that in the control group (1.229 ± 0.425) mm (P<0.001). There were no perforations in either group. Twenty-four months after restoration, there was no significant difference in the SBG, ABH or MBL between the two groups (P>0.05).
Conclusion
After the extraction of teeth from patients with OMS, the inflammation of the maxillary sinus decreased, and the bone height and density in the edentulous area were restored to a certain degree. The effects of sinus floor lifting surgery and implant restoration do not differ between patients with and without OMS.
3.Advances in methods and techniques for the study of polysaccharide in vivo processes and immunomodulatory mechanisms
Chi-yun ZHU ; Ping XIAO ; Yue-yue FANG ; Meng-ting LAI ; Jin-ao DUAN
Acta Pharmaceutica Sinica 2024;59(2):322-335
In recent years, polysaccharides have received much attention because of their high safety and good immunological activity. The study of polysaccharide
4.Nucleophosmin acetylation and construction and expression of its modified sites mutants in breast cancer
Jing-Wei HAO ; Ting PAN ; Yue LI ; Wen-Bin ZHU ; Wen-Bo DUAN ; Li-Kun LIU ; Li-Ling YUE ; Yun-Long LIU ; Xiu-Li GAO
Acta Anatomica Sinica 2024;55(2):196-202
Objective To determine the acetylation level of nucleophosmin(NPM)in female breast cancer and to discuss its function through mutation of modified lysine sites.To construct positive and negative NPM mutants on its acetylated lysine sites and to express them in breast cancer cells.Methods Acetylation level and acetylated lysine sites of NPM in three breast cancer tissues and para-carcinoma tissues were detected by acetylome technology;NPM mutants were constructed by site-directed mutagenesis PCR,specific PCR products were digested by DpnI and transformed into Escherichia coli(E.coli)to obtain specific plasmids for mutants;The accuracy of mutants were verified by double restriction enzyme digestion and sequencing;The mutants were expressed in BT-549 cells by transient transfection and verified by RT-PCR method.Protein expression and acetylation level of NPM were validated by Western blotting;Function of NPM acetylation was analyzed by proteomic detection and bioinformatic analysis.Results The 27th and 32nd lysine of NPM were highly acetylated in breast cancer tissues,which were 2.76 and 2.22 times higher than those in adjacent normal tissues,respectively;The NPM mutants showed the same molecular weight as that of wild type NPM and contained expected mutation sites;Corresponding NPM mRNA levels of BT-549 cells transfected with NPM mutants were significantly increased.With the increase of wild type NPM expression level,NPM acetylation level increased,while decreased after 27th lysine underwent negative mutation.NPM acetylation can significantly change the expression levels of 101 proteins in BT-549 cells,which are enriched in regulation of cellular macromolecule biosynthesis,DNA-template transcription,RNA biosynthesis and RNA metabolism process.Conclusion NPM is highly acetylated in breast cancer and can play a key role in cellular macromolecule biosynthesis,DNA-templated transcription,RNA biosynthesis and RNA metabolism process.
5.Evaluation of the treatment effect on sinus elevation and implant restoration in cases with odontogenic maxil-lary sinusitis after tooth extraction
Yunying ZHU ; Yun LIU ; Ting XU ; Zhenzhen LIU ; Shaoping CAO ; Zhangsong WANG ; Donghui WU
Journal of Prevention and Treatment for Stomatological Diseases 2024;(3):202-208
Objective To investigate the clinical effects of sinus elevation surgery and implant restorationdue to in-sufficient bone massafter tooth extraction in patients with odontogenic maxillary sinusitis(OMS)and to provide a refer-ence for use in clinical practice.Methods This study was reviewed and approved by the Ethics Committee,and in-formed consent was obtained from the patients.Forty-five teeth were extracted from patients with OMS in the maxillary posterior area(the study group).Sinus elevation and implantation were performed due to insufficient bone height in the implant area 6-8 months after tooth extraction in the study group.Forty-eight teeth were extracted from patients without"OMS"in the maxillary posterior area(the control group),and sinus elevation and implantation were performed due to insufficient bone height in the implant area 6-8 months after tooth extraction inthe control group.In the study group,13 cases of discontinuous maxillary sinus floor bone and residual alveolar bone height of the maxillary sinus floor less than 4 mm were addressed with lateral wall sinus elevation,and the other 32 cases were addressed with crest-approach sinus elevation.In the control group,8 cases of residual alveolar bone height less than 4 mm in the maxillary sinus floor were addressed with lateral wall sinus,and the other 40 cases were addressed with crest approach sinus elevation.Restora-tions were placed 6 to 8 months after surgery.The patients were followed up 21 days,3 months,and 8 months after im-plantation and every 6 months after the placement of the restorations.The sinus bone gain(SBG),apical bone height(ABL)and marginal bone loss(MBL)were statistically analyzed 24 months after the restoration.Results The average preoperative mucosal thickness in the 45 patients in the study group was(1.556±0.693)mm,which was significantly larger than that in the control group(1.229±0.425)mm(P<0.001).There were no perforations in either group.Twenty-four months after restoration,there was no significant difference in the SBG,ABH or MBL between the two groups(P>0.05).Conclusion After the extraction of teeth from patients with OMS,the inflammation of the maxillary sinus de-creased,and the bone height and density in the edentulous area were restored to a certain degree.The effects of sinus floor lifting surgery and implant restoration do not differ between patients with and without OMS.
6.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]
7.Risk factors of gastrointestinal bleeding after type A aortic dissection
Shi-Si LI ; Chun-Shui LIANG ; Tian-Bo LI ; Yun ZHU ; Han-Ting LIU ; Xing-Lu WANG ; Si ZHANG ; Rui-Yan MA
Journal of Regional Anatomy and Operative Surgery 2024;33(6):497-500
Objective To analyze the risk factors of gastrointestinal bleeding in patients with type A aortic dissection(TAAD)after Sun's operation.Methods The clinical data of 87 patients who underwent TAAD Sun's operation in our hospital from March 2021 to June 2022 were retrospectively analyzed.They were divided into the bleeding group and the non-bleeding group according to whether there was gastrointestinal bleeding after operation.The clinical data of patients in the two groups was compared and analyzed.The binary Logistic regression analysis was used to analyze the risk factors of gastrointestinal bleeding.The clinical predictor of postoperative gastrointestinal bleeding was analyzed by receiver operating characteristic(ROC)curve.Results In this study,there were 40 cases of postoperative gastrointestinal bleeding(the bleeding group)and 47 cases of non-bleeding(the non-bleeding group).Compared with the non-bleeding group,the bleeding group had a shorter onset time,a higher proportion of patients with hypertension history,a higher preoperative creatinine abnormality rate,more intraoperative blood loss,longer postoperative mechanical ventilation time,higher postoperative infection rate,and higher poor prognosis rate,with statistically significant differences(P<0.05).There was no statistically significant difference in the gender,age,gastrointestinal diseases history,smoking history,preoperative platelets,preoperative international normalized ratio(INR),preoperative alanine aminotransferase(ALT),preoperative aspartate aminotransferase(AST),preoperative γ-glutamyl transpeptidase(GGT),preoperative dissection involving abdominal aorta,operation time,intraoperative cardiopulmonary bypass time,intraoperative circulatory arrest time,intraoperative aortic occlusion time or intraoperative blood transfusion rate.Logistic regression analysis showed that hypertension history(OR=2.468,95%CI:0.862 to 7.067,P=0.037),preoperative creatinine>105 μmol/L(OR=3.970,95%CI:1.352 to 11.659,P=0.011),long postoperative mechanical ventilation time(OR=1.015,95%CI:0.094 to 1.018,P=0.041)and postoperative infection(OR=3.435,95%CI:0.991 to 11.900,P=0.012)were the independent risk factors for postoperative gastrointestinal bleeding in TAAD patients.ROC curve showed that the postoperative mechanical ventilation time exceeding 64 hours were the clinical predictor of postoperative gastrointestinal bleeding in TAAD patients.Conclusion The prognosis of TAAD patients with postoperative gastrointestinal bleeding after Sun's operation is poor.Hypertension history,preoperative acute renal insufficiency,long postoperative mechanical ventilation time and postoperative infection are closely related to postoperative gastrointestinal bleeding in TAAD patients after operation,which should be paid more attention to,and corresponding evaluation,early identification and early intervention should be made to improve the prognosis of patients.
8.Evaluation of the treatment effect on sinus elevation and implant restoration in cases with odontogenic maxil-lary sinusitis after tooth extraction
Yunying ZHU ; Yun LIU ; Ting XU ; Zhenzhen LIU ; Shaoping CAO ; Zhangsong WANG ; Donghui WU
Journal of Prevention and Treatment for Stomatological Diseases 2024;(3):202-208
Objective To investigate the clinical effects of sinus elevation surgery and implant restorationdue to in-sufficient bone massafter tooth extraction in patients with odontogenic maxillary sinusitis(OMS)and to provide a refer-ence for use in clinical practice.Methods This study was reviewed and approved by the Ethics Committee,and in-formed consent was obtained from the patients.Forty-five teeth were extracted from patients with OMS in the maxillary posterior area(the study group).Sinus elevation and implantation were performed due to insufficient bone height in the implant area 6-8 months after tooth extraction in the study group.Forty-eight teeth were extracted from patients without"OMS"in the maxillary posterior area(the control group),and sinus elevation and implantation were performed due to insufficient bone height in the implant area 6-8 months after tooth extraction inthe control group.In the study group,13 cases of discontinuous maxillary sinus floor bone and residual alveolar bone height of the maxillary sinus floor less than 4 mm were addressed with lateral wall sinus elevation,and the other 32 cases were addressed with crest-approach sinus elevation.In the control group,8 cases of residual alveolar bone height less than 4 mm in the maxillary sinus floor were addressed with lateral wall sinus,and the other 40 cases were addressed with crest approach sinus elevation.Restora-tions were placed 6 to 8 months after surgery.The patients were followed up 21 days,3 months,and 8 months after im-plantation and every 6 months after the placement of the restorations.The sinus bone gain(SBG),apical bone height(ABL)and marginal bone loss(MBL)were statistically analyzed 24 months after the restoration.Results The average preoperative mucosal thickness in the 45 patients in the study group was(1.556±0.693)mm,which was significantly larger than that in the control group(1.229±0.425)mm(P<0.001).There were no perforations in either group.Twenty-four months after restoration,there was no significant difference in the SBG,ABH or MBL between the two groups(P>0.05).Conclusion After the extraction of teeth from patients with OMS,the inflammation of the maxillary sinus de-creased,and the bone height and density in the edentulous area were restored to a certain degree.The effects of sinus floor lifting surgery and implant restoration do not differ between patients with and without OMS.
9.Evaluation of the treatment effect on sinus elevation and implant restoration in cases with odontogenic maxil-lary sinusitis after tooth extraction
Yunying ZHU ; Yun LIU ; Ting XU ; Zhenzhen LIU ; Shaoping CAO ; Zhangsong WANG ; Donghui WU
Journal of Prevention and Treatment for Stomatological Diseases 2024;(3):202-208
Objective To investigate the clinical effects of sinus elevation surgery and implant restorationdue to in-sufficient bone massafter tooth extraction in patients with odontogenic maxillary sinusitis(OMS)and to provide a refer-ence for use in clinical practice.Methods This study was reviewed and approved by the Ethics Committee,and in-formed consent was obtained from the patients.Forty-five teeth were extracted from patients with OMS in the maxillary posterior area(the study group).Sinus elevation and implantation were performed due to insufficient bone height in the implant area 6-8 months after tooth extraction in the study group.Forty-eight teeth were extracted from patients without"OMS"in the maxillary posterior area(the control group),and sinus elevation and implantation were performed due to insufficient bone height in the implant area 6-8 months after tooth extraction inthe control group.In the study group,13 cases of discontinuous maxillary sinus floor bone and residual alveolar bone height of the maxillary sinus floor less than 4 mm were addressed with lateral wall sinus elevation,and the other 32 cases were addressed with crest-approach sinus elevation.In the control group,8 cases of residual alveolar bone height less than 4 mm in the maxillary sinus floor were addressed with lateral wall sinus,and the other 40 cases were addressed with crest approach sinus elevation.Restora-tions were placed 6 to 8 months after surgery.The patients were followed up 21 days,3 months,and 8 months after im-plantation and every 6 months after the placement of the restorations.The sinus bone gain(SBG),apical bone height(ABL)and marginal bone loss(MBL)were statistically analyzed 24 months after the restoration.Results The average preoperative mucosal thickness in the 45 patients in the study group was(1.556±0.693)mm,which was significantly larger than that in the control group(1.229±0.425)mm(P<0.001).There were no perforations in either group.Twenty-four months after restoration,there was no significant difference in the SBG,ABH or MBL between the two groups(P>0.05).Conclusion After the extraction of teeth from patients with OMS,the inflammation of the maxillary sinus de-creased,and the bone height and density in the edentulous area were restored to a certain degree.The effects of sinus floor lifting surgery and implant restoration do not differ between patients with and without OMS.
10.Evaluation of the treatment effect on sinus elevation and implant restoration in cases with odontogenic maxil-lary sinusitis after tooth extraction
Yunying ZHU ; Yun LIU ; Ting XU ; Zhenzhen LIU ; Shaoping CAO ; Zhangsong WANG ; Donghui WU
Journal of Prevention and Treatment for Stomatological Diseases 2024;(3):202-208
Objective To investigate the clinical effects of sinus elevation surgery and implant restorationdue to in-sufficient bone massafter tooth extraction in patients with odontogenic maxillary sinusitis(OMS)and to provide a refer-ence for use in clinical practice.Methods This study was reviewed and approved by the Ethics Committee,and in-formed consent was obtained from the patients.Forty-five teeth were extracted from patients with OMS in the maxillary posterior area(the study group).Sinus elevation and implantation were performed due to insufficient bone height in the implant area 6-8 months after tooth extraction in the study group.Forty-eight teeth were extracted from patients without"OMS"in the maxillary posterior area(the control group),and sinus elevation and implantation were performed due to insufficient bone height in the implant area 6-8 months after tooth extraction inthe control group.In the study group,13 cases of discontinuous maxillary sinus floor bone and residual alveolar bone height of the maxillary sinus floor less than 4 mm were addressed with lateral wall sinus elevation,and the other 32 cases were addressed with crest-approach sinus elevation.In the control group,8 cases of residual alveolar bone height less than 4 mm in the maxillary sinus floor were addressed with lateral wall sinus,and the other 40 cases were addressed with crest approach sinus elevation.Restora-tions were placed 6 to 8 months after surgery.The patients were followed up 21 days,3 months,and 8 months after im-plantation and every 6 months after the placement of the restorations.The sinus bone gain(SBG),apical bone height(ABL)and marginal bone loss(MBL)were statistically analyzed 24 months after the restoration.Results The average preoperative mucosal thickness in the 45 patients in the study group was(1.556±0.693)mm,which was significantly larger than that in the control group(1.229±0.425)mm(P<0.001).There were no perforations in either group.Twenty-four months after restoration,there was no significant difference in the SBG,ABH or MBL between the two groups(P>0.05).Conclusion After the extraction of teeth from patients with OMS,the inflammation of the maxillary sinus de-creased,and the bone height and density in the edentulous area were restored to a certain degree.The effects of sinus floor lifting surgery and implant restoration do not differ between patients with and without OMS.


Result Analysis
Print
Save
E-mail