OBJECTIVES: To compare the commonly used methods for analyzing treatment switching in clinical trials to facilitate selection of optimal methods in different scenarios. METHODS: Based on the data characteristics of patient conversion in oncology clinical trials, we simulated the survival time of patients across different scenarios and compared the bias, mean square error and coverages of the treatment effects derived from different methods. RESULTS: The sample size had an almost negligible impact on the outcomes of the various methods. Compared to conventional methods, more complex methods (RPSFTM, IPCW, TSE, and IPE) resulted in lower errors across different scenarios. The IPCW method could cause a significant increase in errors in cases where the probability of conversion was high. The TSE method had the lowest error and mean squared error when the risk was low and the probability of conversion was high. The IPE method had an obvious advantage in the scenario with a low probability of conversion, but it may slightly underestimate the treatment effect when the inflation factor was small. CONCLUSIONS The choice of a specific method for analyzing cohort transition should be made based on considerations of both the probability of conversion and inflation factor in different scenarios.
Humans ; Clinical Trials as Topic/methods* ; Neoplasms/therapy*

BACKGROUND:Graphene oxide,with its excellent physical and chemical properties and biocompatibility,can promote the differentiation of osteoblasts and inhibit the proliferation of bacteria,which will hopefully improve the success rate of implant restoration.OBJECTIVE:To summarize the research progress of graphene oxide in the field of dental implant restoration.METHODS:The related articles published by CNKI,WanFang Database,ScienceDirect,and PubMed from January 2000 to June 2024 were searched by computer.The keywords were"graphene oxide,dental implantation,biocompatibility,antibacterial mechanism,osteoblasts,mechanical properties,chemical properties"in Chinese and English.By reading the titles and abstracts,we preliminarily screened out the documents irrelevant to the topic of the article.According to the inclusion and exclusion criteria,65 documents were finally included for analysis.RESULTS AND CONCLUSION:Graphene oxide can increase the innate immune protection response of the body through its own antibacterial and drug-loaded antibacterial abilities,thus inhibiting the occurrence and development of periimplant inflammation.Graphene oxide can promote the proliferation and differentiation of bone marrow mesenchymal stem cells,enhance the proliferation of osteoblasts and vascular endothelial cells,inhibit the proliferation of osteoclasts,increase the rate of bone bonding between implants and alveolar bones,and contribute to the formation and stability of bone around implants.Graphene oxide can promote the combination of implant and gingival tissue,and reduce the occurrence of inflammation.Graphene oxide has low toxicity,and its biological safety needs further study.Graphene oxide coating endows the surface of titanium implant with excellent physical and chemical properties,which can greatly reduce the occurrence of complications such as implant fracture and prolong the survival time of implant.

Objective·To investigate the therapeutic effect of combined vitamin D and docosahexaenoic acid(DHA)supplementation on preschool children with attention deficit hyperactivity disorder(ADHD).Methods·From April 2021 to May 2021,a total of 1 412 children aged 4 to 6 years from eight kindergartens in Pudong New Area of Shanghai,including Tangqiao Street,Chuansha Town,and Heqing Town,were randomly selected by stratified cluster random sampling method.Attention and hyperactivity symptom assessment was performed using the Conner's Scale,Diagnosis and Statistical Manual of Mental Disorders(fifth edition,DSM-Ⅴ),and Swanson,Nolan,and Pelham(version Ⅳ,SNAP-Ⅳ)Scale,and other neurodevelopmental disorders were excluded using the Wechsler Intelligence Scale.A total of 82 preschool children with ADHD were enrolled,and after fully informing them of the intervention measures,they were divided into an intervention group(n=64)and a control group(n=18)based on their parents' choice.The control group received routine health education.In addition to routine health education,the intervention group received daily supplementation of Vitamin D(800 IU)and DHA(400 mg).Venous blood samples were collected from both groups at baseline,3 months,and 12 months for the measurement of serum 25 hydroxy vitamin D[25(OH)D]and DHA levels.ADHD symptoms were evaluated using Conner's Scale,SNAP-Ⅳ Scale,and DSM-Ⅴ.Results·After 3 and 12 months of intervention in the intervention group,serum 25(OH)D levels and DHA levels were significantly higher(P<0.05),the ADHD symptom scores,including impulsivity-hyperactivity and hyperactivity index scores in Conner's Scale,the attention and hyperactivity/impulsivity scores in SNAP-Ⅳ Scale,and the attention and hyperactivity/impulsivity scores in DSM-Ⅴ,were significantly reduced compared with the scores before the intervention(P<0.05).There was no significant difference in serum 25(OH)D and DHA levels,or ADHD symptom scores,at the 3-and 12-month follow-ups compared to baseline.After 3 months of nutritional intervention in the intervention group,the hyperactivity/impulsivity scores in SNAP-Ⅳ Scale and DSM-Ⅴ were significantly improved compared to the control group(P<0.05).After 12 months of intervention,conduct problems,impulsive-hyperactivity and hyperactivity index scores in Conner's Scale,and hyperactivity/impulsivity scores in SNAP-Ⅳ Scale and DSM-Ⅴ showed significant improvement compared to the control group(P<0.05).Conclusion·Combined supplementation with vitamin D and DHA significantly improves serum 25(OH)D and DHA levels and alleviates ADHD symptoms in preschool children.

BACKGROUND:Graphene oxide,with its excellent physical and chemical properties and biocompatibility,can promote the differentiation of osteoblasts and inhibit the proliferation of bacteria,which will hopefully improve the success rate of implant restoration.OBJECTIVE:To summarize the research progress of graphene oxide in the field of dental implant restoration.METHODS:The related articles published by CNKI,WanFang Database,ScienceDirect,and PubMed from January 2000 to June 2024 were searched by computer.The keywords were"graphene oxide,dental implantation,biocompatibility,antibacterial mechanism,osteoblasts,mechanical properties,chemical properties"in Chinese and English.By reading the titles and abstracts,we preliminarily screened out the documents irrelevant to the topic of the article.According to the inclusion and exclusion criteria,65 documents were finally included for analysis.RESULTS AND CONCLUSION:Graphene oxide can increase the innate immune protection response of the body through its own antibacterial and drug-loaded antibacterial abilities,thus inhibiting the occurrence and development of periimplant inflammation.Graphene oxide can promote the proliferation and differentiation of bone marrow mesenchymal stem cells,enhance the proliferation of osteoblasts and vascular endothelial cells,inhibit the proliferation of osteoclasts,increase the rate of bone bonding between implants and alveolar bones,and contribute to the formation and stability of bone around implants.Graphene oxide can promote the combination of implant and gingival tissue,and reduce the occurrence of inflammation.Graphene oxide has low toxicity,and its biological safety needs further study.Graphene oxide coating endows the surface of titanium implant with excellent physical and chemical properties,which can greatly reduce the occurrence of complications such as implant fracture and prolong the survival time of implant.

Objective·To investigate the therapeutic effect of combined vitamin D and docosahexaenoic acid(DHA)supplementation on preschool children with attention deficit hyperactivity disorder(ADHD).Methods·From April 2021 to May 2021,a total of 1 412 children aged 4 to 6 years from eight kindergartens in Pudong New Area of Shanghai,including Tangqiao Street,Chuansha Town,and Heqing Town,were randomly selected by stratified cluster random sampling method.Attention and hyperactivity symptom assessment was performed using the Conner's Scale,Diagnosis and Statistical Manual of Mental Disorders(fifth edition,DSM-Ⅴ),and Swanson,Nolan,and Pelham(version Ⅳ,SNAP-Ⅳ)Scale,and other neurodevelopmental disorders were excluded using the Wechsler Intelligence Scale.A total of 82 preschool children with ADHD were enrolled,and after fully informing them of the intervention measures,they were divided into an intervention group(n=64)and a control group(n=18)based on their parents' choice.The control group received routine health education.In addition to routine health education,the intervention group received daily supplementation of Vitamin D(800 IU)and DHA(400 mg).Venous blood samples were collected from both groups at baseline,3 months,and 12 months for the measurement of serum 25 hydroxy vitamin D[25(OH)D]and DHA levels.ADHD symptoms were evaluated using Conner's Scale,SNAP-Ⅳ Scale,and DSM-Ⅴ.Results·After 3 and 12 months of intervention in the intervention group,serum 25(OH)D levels and DHA levels were significantly higher(P<0.05),the ADHD symptom scores,including impulsivity-hyperactivity and hyperactivity index scores in Conner's Scale,the attention and hyperactivity/impulsivity scores in SNAP-Ⅳ Scale,and the attention and hyperactivity/impulsivity scores in DSM-Ⅴ,were significantly reduced compared with the scores before the intervention(P<0.05).There was no significant difference in serum 25(OH)D and DHA levels,or ADHD symptom scores,at the 3-and 12-month follow-ups compared to baseline.After 3 months of nutritional intervention in the intervention group,the hyperactivity/impulsivity scores in SNAP-Ⅳ Scale and DSM-Ⅴ were significantly improved compared to the control group(P<0.05).After 12 months of intervention,conduct problems,impulsive-hyperactivity and hyperactivity index scores in Conner's Scale,and hyperactivity/impulsivity scores in SNAP-Ⅳ Scale and DSM-Ⅴ showed significant improvement compared to the control group(P<0.05).Conclusion·Combined supplementation with vitamin D and DHA significantly improves serum 25(OH)D and DHA levels and alleviates ADHD symptoms in preschool children.

Objective:To summarise and analyse the experience in the diagnosis and management of abdominal aortic endograft infection in recent years.Methods:Retrospectively summarised and analysed the general data, clinical presentation, laboratory and imaging findings, causative organisms and treatment choices of 14 patients with abdominal aortic endograft infection treated in Beijing Friendship Hospital, Capital Medical University, from January 2018 to June 2024, and analysed the prognosis of the patients and the risk factors associated with prognosis.Results:Positive bacterial cultures were 10 out of 14 patients. One non-operatively treated patient died of infectious toxic shock. Thirteen surgically treated patients underwent axillary-bifemoral artery bypass, removal of the infected stent, and closure of the aortic stump. Four of the 13 cases had combined aortoenteric fistula, 3 cases underwent one-stage enterocutaneous fistula repair, 1 case only fistula drainage, 3 cases of gastrojejunal anastomosis, all of them underwent gastric or jejunal nutrient tube implantation. Two of the 13 patients had combined the infection foci spread to the renal artery openings. To save the kidney, intraoperative left kidney autologous renal transplantation was performed in 1 case, and autologous saphenous vein reconstruction from celiac trunk artery-left renal artery and superior mesenteric artery-right renal artery was performed in the other case. All 14 patients were retrospectively summarised and followed up in August 2024, with 5 deaths in the early postoperative period (< 3 months), 3 deaths in the mid- to long-term period (≥3 months), and 5 survivors, with a median follow-up time of 2 years (1-5 years) for surviving patients. Among the 13 operated patients, 4 cases were combined with aortoenteric fistula, and 3 cases died in the early postoperative period; 4 cases of abdominal aortic infection foci involving renal artery openings, 2 cases of early postoperative death; 4 cases with pleural effusion, 4 cases died in the early postoperative period; 2 cases of combined creatinine elevation, 2 cases of early postoperative death; 2 cases of postoperative infection of artificial blood vessels.Conclusions:Abdominal aortic endograft infection are aggressive. The risk of early death is increased in patients who are elderly, in poor general condition, with aortoenteric fistula or with pre-existing cardiac, pulmonary, hepatic and renal insufficiency, but surgery based on adequate anti-infective therapy remains an effective means of saving the patient′s life.

Objective To investigate the reasons for the inconsistent results between the vertical auto profile(VAP)method and bio-chemical homogeneous phase(BHP)method in detecting plasma low-density lipoprotein cholesterol(LDL-C),and provide experimen-tal basis for the accurate and quantitative detection of plasma LDL-C levels.Methods A total of 360 plasma samples from diabetes mellitus patients combined with carotid plaque admitted to the Department of Endocrinology of Ningbo Yinzhou Hospital of Traditional Chinese Medicine during January,2022 and January,2023 were collected.The LDL-C levels of these samples were detected by the VAP method and BHP method,respectively.The VAP method uses software to automatically calculate the area under the LDL-C curve after centrifugation of the sample as the LDL-C level(LDL-CVAP)and the BHP method directly detects the LDL-C level(LDL-CBHP)by the special surfactant method.360 samples were divided into the consistent group(group A)and inconsistent group(group B)ac-cording to the relative deviation between the LDL-CBHP and LDL-CVAP methods.Group B was further divided into the LDL-CBHP on the high side group(Group B1)and LDL-CBHP on the low side group(Group B2).Groups B1 and B2 were divided into B1-1,B1-2,B1-3 and B2-1 groups based on the degree of relative deviation.The percentages of samples and levels of lipoprotein a cholesterol[Lp(a)-C],intermediate-density lipoprotein cholesterol(IDL-C),Lp(a)-C and IDL-C[Lp(a)-C+IDL-C],very low-density lipo-protein cholesterol(VLDL-C),total cholesterol(TC)and total triglyceride(TG)in each group were compared.Results The LDL-CBHP levels of 360 samples were significantly higher than that of LDL-CVAP(P＜0.01).The percentage of samples in group B was significantly higher than that in group A,and that of group B1 was significantly higher than that of group B2(P＜0.05).The levels of Lp(a)-C,IDL-C and Lp(a)-C+IDL-C in groups B1-1,B1-2,and B1-3 were significantly higher than those in group A(P＜0.01).The relative deviation between LDL-CBHP and LDL-CVAP in 360 samples was significantly positively correlated with the levels of Lp(a)-C,IDL-C,and Lp(a)-C+IDL-C(P＜0.01).The maximum correlation coefficient was found in Lp(a)-C+IDL-C.Conclusion The results of plasma LDL-C in diabetes mellitus patients combined with carotid plaque detected by the BHP method are significantly different from those detected by the VAP method,which mainly shows that the results of the BHP method are on the high side.The higher the level of plasma Lp(a)-C+IDL-C,the greater the relative deviation between the BHP method and VAP method.The reason for the high results of LDL-C detected by the BHP method may be related to the fact that LDL-CBHP contains irremovable Lp(a)-C and cholesterol carried by IDL-C.The VAP method can be used as an accurate method for detecting real LDL-C without Lp(a)-C and IDL-C.

AIM:To investigate the role and mechanism of histone demethylase lysine-specific demethylase 5A(KDM5A)in regulating the Notch signaling pathway in particulate matter 2.5(PM2.5)-induced cortical damage in off-spring mice.METHODS:A pregnancy PM2.5 exposure model was established using intratracheal nebulization.Pregnant mice were randomly divided into PBS control group and PM2.5 exposure group.The cortices of offspring mice were isolated 14 d after birth.Golgi staining,electron microscopy and other methods were used to detect damage to neurons and chroma-tin in the cortex.Western blot,RT-qPCR and immunofluorescence staining were used to detect the mRNA and protein ex-pression of KDM5A in the cortex,and the distribution of KDM5A co-localized with neural cells.A PM2.5-treated PC12 cell injury model was established to detect changes in cell viability and the expression of proteins related to cell proliferation and apoptosis.Further,Western blot,RT-qPCR and immunofluorescence staining were used to detect the mRNA and pro-tein expression of KDM5A,the distribution of KDM5A co-localized with neurons,and changes in the protein level of his-tone H3K4me3.Bioinformatics methods were used to predict the interaction between KDM5A and Notch1,which was fur-ther validated by transfection experiments.In both in vivo and in vitro PM2.5 exposure models,changes in key molecules of the Notch signaling pathway and the co-expression of Notch1 with neural cells in the cortices of 14-day-old offspring mice and PC12 cells were detected.RESULTS:Prenatal PM2.5 exposure during pregnant led to a reduction in the number of neurons and decreased dentritic complexity in the cerebral cortex of offspring at 14 d after birth.It also caused abnormal chromatin condensation within neuronal nuclei,decreased mRNA and protein expression of KDM5A protein in the cortex,increased H3K4me3 protein levels(P＜0.05),and a significant reduction in KDM5A/NeuN double-positive cells.Expo-sure to PM2.5 also resulted in decreased viability and proliferation,and increased apoptosis of PC12 cells,with reduced ex-pression of KDM5A mRNA and protein,increased H3K4me3 protein expression(P＜0.05),and a reduction in the num-ber of KDM5A/MAP-2 double-positive cells.Bioinformatics analysis and transfection experiments in PC12 cells revealed that Notch1 is a downstream target gene of KDM5A.Further in vivo and in vitro experiments found that PM2.5 exposure lead to decreased mRNA and protein expression of key Notch signaling molecules Notch1,Jagged1 and Hes1,and reduced numbers of Notch1/NeuN and Notch1/MAP-2 double-positive cells.CONCLUSION:Exposure to PM2.5 can lead to abnor-mal expression of KDM5A in the offspring's cerebral cortex,which may cause neuronal damage by down-regulating the Notch signaling pathway,a downstream target.This could be one of the significant factors contributing to the neurodevelop-mental disorders in offspring exposed to PM2.5 during pregnancy.

AIM:To investigate the role and mechanism of histone demethylase lysine-specific demethylase 5A(KDM5A)in regulating the Notch signaling pathway in particulate matter 2.5(PM2.5)-induced cortical damage in off-spring mice.METHODS:A pregnancy PM2.5 exposure model was established using intratracheal nebulization.Pregnant mice were randomly divided into PBS control group and PM2.5 exposure group.The cortices of offspring mice were isolated 14 d after birth.Golgi staining,electron microscopy and other methods were used to detect damage to neurons and chroma-tin in the cortex.Western blot,RT-qPCR and immunofluorescence staining were used to detect the mRNA and protein ex-pression of KDM5A in the cortex,and the distribution of KDM5A co-localized with neural cells.A PM2.5-treated PC12 cell injury model was established to detect changes in cell viability and the expression of proteins related to cell proliferation and apoptosis.Further,Western blot,RT-qPCR and immunofluorescence staining were used to detect the mRNA and pro-tein expression of KDM5A,the distribution of KDM5A co-localized with neurons,and changes in the protein level of his-tone H3K4me3.Bioinformatics methods were used to predict the interaction between KDM5A and Notch1,which was fur-ther validated by transfection experiments.In both in vivo and in vitro PM2.5 exposure models,changes in key molecules of the Notch signaling pathway and the co-expression of Notch1 with neural cells in the cortices of 14-day-old offspring mice and PC12 cells were detected.RESULTS:Prenatal PM2.5 exposure during pregnant led to a reduction in the number of neurons and decreased dentritic complexity in the cerebral cortex of offspring at 14 d after birth.It also caused abnormal chromatin condensation within neuronal nuclei,decreased mRNA and protein expression of KDM5A protein in the cortex,increased H3K4me3 protein levels(P＜0.05),and a significant reduction in KDM5A/NeuN double-positive cells.Expo-sure to PM2.5 also resulted in decreased viability and proliferation,and increased apoptosis of PC12 cells,with reduced ex-pression of KDM5A mRNA and protein,increased H3K4me3 protein expression(P＜0.05),and a reduction in the num-ber of KDM5A/MAP-2 double-positive cells.Bioinformatics analysis and transfection experiments in PC12 cells revealed that Notch1 is a downstream target gene of KDM5A.Further in vivo and in vitro experiments found that PM2.5 exposure lead to decreased mRNA and protein expression of key Notch signaling molecules Notch1,Jagged1 and Hes1,and reduced numbers of Notch1/NeuN and Notch1/MAP-2 double-positive cells.CONCLUSION:Exposure to PM2.5 can lead to abnor-mal expression of KDM5A in the offspring's cerebral cortex,which may cause neuronal damage by down-regulating the Notch signaling pathway,a downstream target.This could be one of the significant factors contributing to the neurodevelop-mental disorders in offspring exposed to PM2.5 during pregnancy.

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*