BACKGROUND The relation between orthodontic treatment and temporomandibular disorders(TMDs)is under debate;the management of TMD during orthodontic treatment has always been a challenge.If TMD symptoms occur during or...BACKGROUND The relation between orthodontic treatment and temporomandibular disorders(TMDs)is under debate;the management of TMD during orthodontic treatment has always been a challenge.If TMD symptoms occur during orthodontic treatment,an immediate pause of orthodontic adjustments is recommended;the treatment can resume when the symptoms are managed and stabilized.CASE SUMMARY This case report presents a patient(26-year-old,female)with angle class I,skeletal class II and TMDs.The treatment was a hybrid of clear aligners,fixed appliances and temporary anchorage devices(TADs).After 3 mo resting and treatment on her TMD,the patient’s TMD symptom alleviated,but her anterior occlusion displayed deep overbite.Therefore,the fixed appliances with TAD were used to correct the anterior deep-bite and level maxillary and mandibular deep curves.After the levelling,the patient showed dual bite with centric relation and maximum intercuspation discrepancy on her occlusion.After careful examination of temporomandibular joints(TMJ)position,the stable bite splint and Invisible Mandibular Advancement appliance were used to reconstruct her occlusion.Eventually,the improved facial appearance and relatively stable occlusion were achieved.The 1-year follow-up records showed there was no obvious change in TMJ morphology,and her occlusion was stable.CONCLUSION TMD screening and monitoring is of great clinical importance in the TMD susceptible patients.Hybrid treatment with clear aligners and fixed appliances and TADs is an effective treatment modality for the complex cases.展开更多
Objective:Chronic kidney disease(CKD)is a progressive disorder characterized by intricate structural and functional alterations in the kidneys,attributable to diverse causative factors.Notably,the therapeutic promise ...Objective:Chronic kidney disease(CKD)is a progressive disorder characterized by intricate structural and functional alterations in the kidneys,attributable to diverse causative factors.Notably,the therapeutic promise of miR-145-5p in addressing renal pathologies has been discerned.This investigation seeks to elucidate the functional role of miR-145-5p in injured kidneys by subjecting human glomerular mesangial cells(HGMCs)to stimulation with Angiotensin II(AngII).Materials and Methods:Cellular viability and the levels of inflammatory mediators were evaluated utilizing Cell Counting Kit-8(CCK-8),quantitative real-time polymerase chain reaction(qRT-PCR),and western blot methodologies,both in the presence of AngII incubation and in scenarios of miR-145p overexpression and downregulation.Furthermore,the cell cycle dynamics were elucidated through Fluorescence-activated Cell Sorting(FACS)analysis.Results:AngII incubation induced an upregulation of miR-145-5p and inflammatory factors including Intercellular Adhesion Molecule 1(ICAM-1),Interleukin 6(IL-6),Interleukin 8(IL-8),and Interleukin 1β(IL-1β).Additionally,it elevated the expression of Cyclin A2,Cyclin D1,and the G2/M cell cycle ratio.Conversely,inhibition of miR-145-5p heightened the levels of inflammatory factors and cell cycle regulators induced by AngII incubation.Reduced expression of miR-145-5p correlated with a downregulation of Interleukin 10(IL-10)expression,concurrently promoting HGMC proliferation under AngII stimulation.Moreover,ectopic miR-145-5p expression demonstrated a reduction in inflammatory factors,cell cyclin regulators,G2/M cell cycle ratio,and overall proliferation.Conclusion:MiR-145-5p exhibited inhibitory effects on the inflammatory response and proliferation induced by Angiotensin II in HGMCs,showcasing its potential as a therapeutic avenue for the treatment of kidney injury.展开更多
BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment options.AIM To explore the efficacy and safety of nab-paclitaxel plus capecitabine as...BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment options.AIM To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic BTCs.METHODS This open-label,non-randomized,double-center,phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical University.Eligible patients were administered nab-paclitaxel(150 mg/m^(2),day 1)and capecitabine(2000 mg/m^(2),twice daily,days 1-7)in 14-day cycles until experiencing intolerable toxicity or disease progression.The primary outcome was the objective response rate(ORR).The secondary outcomes included the disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and safety.RESULTS A total of 44 patients successfully completed the trial,with a median age of 64.00 years(interquartile range,35.00-76.00),and 26(59.09%)were females.Tumor response assessment was impeded for one patient due to premature demise from tumor hemorrhage.Among the remaining 43 patients undergoing at least one imaging assessment,the ORR was 23.26%[95%confidence interval(CI):11.80%-38.60%],and the DCR was 69.77%(95%CI:53.90%-82.80%).The median OS was 14.1 months(95%CI:8.3-19.9),and the median PFS was 4.4 months(95%CI:2.5-6.3).A total of 41 patients(93.18%)experienced at least one adverse event(AE),with 10 patients(22.73%)encountering grade≥3 AEs,and the most frequent AEs of any grade were alopecia(79.50%),leukopenia(54.55%),neutropenia(52.27%),and liver dysfunction(40.91%),and no treatment-related deaths were documented.CONCLUSION Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.展开更多
BACKGROUND The surgeon performing a distal gastrectomy,has an arsenal of reconstruction techniques at his disposal,Billroth II among them.Braun anastomosis performed during a Billroth II procedure has shown evidence o...BACKGROUND The surgeon performing a distal gastrectomy,has an arsenal of reconstruction techniques at his disposal,Billroth II among them.Braun anastomosis performed during a Billroth II procedure has shown evidence of superiority over typical Billroth II,in terms of survival,with no impact on postoperative morbidity and mortality.AIM To compare Billroth II vs Billroth II and Braun following distal gastrectomy,regarding their postoperative course.METHODS Patients who underwent distal gastrectomy during 2002-2021,were separated into two groups,depending on the surgical technique used(Billroth II:74 patients and Billroth II and Braun:28 patients).The daily output of the nasogastric tube(NGT),the postoperative day that NGT was removed and the day the patient started per os feeding were recorded.Postoperative complications were at the same time noted.Data were then statistically analyzed.RESULTS There was difference in the mean NGT removal day and the mean start feeding day.Mean total postoperative NGT output was lower in Braun group(399.17 mL vs 1102.78 mL)and it was statistically significant(P<0.0001).Mean daily postoperative NGT output was also statistically significantly lower in Braun group.According to the postoperative follow up 40 patient experienced bile reflux and alkaline gastritis from the Billroth II group,while 9 patients who underwent Christodoulidis G et al.Billroth II and Braun compared with Billroth II WJM https://www.wjgnet.com 2 March 20,2024 Volume 14 Issue 1 Billroth II and Braun anastomosis were presented with the same conditions(P<0.05).CONCLUSION There was evidence of superiority of Billroth II and Braun vs typical Billroth II in terms of bile reflux,alkaline gastritis and NGT output.展开更多
AIM:To investigate the impacts of angiotensin II(Ang II)on retinal artery changes in apolipoprotein E deficient(apoE^(-/-))mice.METHODS:ApoE^(-/-)male mice were infused by minipumps with Ang II at 1000 ng/kg·min(...AIM:To investigate the impacts of angiotensin II(Ang II)on retinal artery changes in apolipoprotein E deficient(apoE^(-/-))mice.METHODS:ApoE^(-/-)male mice were infused by minipumps with Ang II at 1000 ng/kg·min(Ang II group)or saline(control group)for 28d.They were underwent ophthalmic fundus examination on day 0,14,and 28 of infusion.Histopathologic examination,ribonucleic acid(RNA)sequencing and local Ang II measurement of retinas were conducted.RESULTS:Ophthalmic fundus examination showed Ang II infusion promoted the formation of retinal arterial aneurysm-like lesions on day 28.Optical coherence tomography revealed the ganglion cell and inner plexiform layer(GCIPL)thickness in the control group was significantly thinner than that in Ang II group(P<0.001).Hematoxylin-eosin staining demonstrated diffused swelling of GCIPL layer and its disordered structure in Ang II group.Transmission electron microscopy showed Ang II infusion caused aggravation of atherosclerotic lesions,including increased swelling,roughness,disorganization of the retinal vasculature,and vacuoles formation.RNA-sequencing and gene ontology enrichment analysis demonstrated that the structure and function of cellular membrane might be disturbed and visual function might be compromised by Ang II.The local level of Ang II was higher in Ang II infusion group but did not show significant differences compared to the control group(P=0.086).CONCLUSION:Ang II infusion promotes the formation of retinal arterial aneurysm-like lesions in apoE^(-/-)mice,causing aggravation of atherosclerotic lesions,more severe disorganization of the retinal vasculature and disturbance of the cellular membrane.展开更多
Angiotensin II (Ang II) is the main mediator of the Renin-Angiotensin-System acting on AT<sub>1</sub> and other AT receptors. It is regarded as a pleiotropic agent that induces many actions, including func...Angiotensin II (Ang II) is the main mediator of the Renin-Angiotensin-System acting on AT<sub>1</sub> and other AT receptors. It is regarded as a pleiotropic agent that induces many actions, including functioning as a growth factor, and as a contractile hormone, among others. The aim of this work was to examine the impact of Ang II on the expression and function of α<sub>1</sub>-adrenergic receptors (α<sub>1</sub>-ARs) in cultured rat aorta, and aorta-derived smooth muscle cells. Isolated Wistar rat aorta was incubated for 24 h in DMEM at 37˚C, then subjected to isometric tension and to the action of added norepinephrine, in concentration-response curves. Ang II was added (1 × 10<sup>−5</sup> M), and in some experiments, 5-Methylurapidil (α<sub>1A</sub>-AR antagonist), AH11110A (α<sub>1B</sub>-AR antagonist), or BMY-7378 (α<sub>1D</sub>-AR antagonist), were used to identify the α<sub>1</sub>-AR involved in the response. Desensitization of the contractile response to norepinephrine was observed due to incubation time, and by the Ang II action. α<sub>1D</sub>-AR was protected from desensitization by BMY-7378;while RS-100329 and prazosin partially mitigated desensitization. In another set of experiments, isolated aorta-derived smooth muscle cells were exposed to Ang II and α<sub>1</sub>-ARs proteins were evaluated. α<sub>1D</sub>-AR increased at 30 and 60 min post Ang II exposure, the α<sub>1A</sub>-AR diminished from 1 to 4 h, while α<sub>1B</sub>-AR remained unchanged over 24 h of Ang II exposure. Ang II induced an increase of α<sub>1D</sub>-AR at short times, and BMY-7378 protected α<sub>1D</sub>-AR from desensitization.展开更多
Background:Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic,while immunogenic genes need to be eliminated to improve the immune compatibility between humans and pigs.Curren...Background:Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic,while immunogenic genes need to be eliminated to improve the immune compatibility between humans and pigs.Current knockout strategies are mainly aimed at the genes causing hyperacute immune rejection(HAR)that occurs in the first few hours while adaptive immune reactions orchestrated by CD4 T cell thereafter also cause graft failure,in which process the MHCⅡmolecule plays critical roles.Methods:Thus,we generate a 4-gene(GGTA1,CMAH,β4GalNT2,and CIITA)knockout pig by CRISPR/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions simultaneously.Results:We successfully obtained 4KO piglets with deficiency in all alleles of genes,and at cellular and tissue levels.Additionally,the safety of our animals after gene editing was verified by using whole-genome sequencing and karyotyping.Piglets have survived for more than one year in the barrier,and also survived for more than 3 months in the conventional environment,suggesting that the piglets without MHCⅡcan be raised in the barrier and then gradually mated in the conventional environment.Conclusions:4KO piglets have lower immunogenicity,are safe in genomic level,and are easier to breed than the model with both MHCⅠandⅡdeletion.展开更多
基金Natural Science Foundation of Jiangsu Province, No. SBK2021021787the Major Project of the Health Commission ofJiangsu Province, No. ZD2022025and the Key Project of the Nanjing Health Commission, No. ZKX20048.
文摘BACKGROUND The relation between orthodontic treatment and temporomandibular disorders(TMDs)is under debate;the management of TMD during orthodontic treatment has always been a challenge.If TMD symptoms occur during orthodontic treatment,an immediate pause of orthodontic adjustments is recommended;the treatment can resume when the symptoms are managed and stabilized.CASE SUMMARY This case report presents a patient(26-year-old,female)with angle class I,skeletal class II and TMDs.The treatment was a hybrid of clear aligners,fixed appliances and temporary anchorage devices(TADs).After 3 mo resting and treatment on her TMD,the patient’s TMD symptom alleviated,but her anterior occlusion displayed deep overbite.Therefore,the fixed appliances with TAD were used to correct the anterior deep-bite and level maxillary and mandibular deep curves.After the levelling,the patient showed dual bite with centric relation and maximum intercuspation discrepancy on her occlusion.After careful examination of temporomandibular joints(TMJ)position,the stable bite splint and Invisible Mandibular Advancement appliance were used to reconstruct her occlusion.Eventually,the improved facial appearance and relatively stable occlusion were achieved.The 1-year follow-up records showed there was no obvious change in TMJ morphology,and her occlusion was stable.CONCLUSION TMD screening and monitoring is of great clinical importance in the TMD susceptible patients.Hybrid treatment with clear aligners and fixed appliances and TADs is an effective treatment modality for the complex cases.
基金This work was supported by Nantong Science and Technology Project(MS22022012,MS12021039,MS12018020,MS12018041,JC2020040)Jiangsu Provincial Laboratory Animal Association(DWXH202116)+1 种基金the Doctoral Scientific Research Foundation of Nantong University(135420505015,135422505037)National College Students’Innovation and Entrepreneurship Training Program(202110304036Z).
文摘Objective:Chronic kidney disease(CKD)is a progressive disorder characterized by intricate structural and functional alterations in the kidneys,attributable to diverse causative factors.Notably,the therapeutic promise of miR-145-5p in addressing renal pathologies has been discerned.This investigation seeks to elucidate the functional role of miR-145-5p in injured kidneys by subjecting human glomerular mesangial cells(HGMCs)to stimulation with Angiotensin II(AngII).Materials and Methods:Cellular viability and the levels of inflammatory mediators were evaluated utilizing Cell Counting Kit-8(CCK-8),quantitative real-time polymerase chain reaction(qRT-PCR),and western blot methodologies,both in the presence of AngII incubation and in scenarios of miR-145p overexpression and downregulation.Furthermore,the cell cycle dynamics were elucidated through Fluorescence-activated Cell Sorting(FACS)analysis.Results:AngII incubation induced an upregulation of miR-145-5p and inflammatory factors including Intercellular Adhesion Molecule 1(ICAM-1),Interleukin 6(IL-6),Interleukin 8(IL-8),and Interleukin 1β(IL-1β).Additionally,it elevated the expression of Cyclin A2,Cyclin D1,and the G2/M cell cycle ratio.Conversely,inhibition of miR-145-5p heightened the levels of inflammatory factors and cell cycle regulators induced by AngII incubation.Reduced expression of miR-145-5p correlated with a downregulation of Interleukin 10(IL-10)expression,concurrently promoting HGMC proliferation under AngII stimulation.Moreover,ectopic miR-145-5p expression demonstrated a reduction in inflammatory factors,cell cyclin regulators,G2/M cell cycle ratio,and overall proliferation.Conclusion:MiR-145-5p exhibited inhibitory effects on the inflammatory response and proliferation induced by Angiotensin II in HGMCs,showcasing its potential as a therapeutic avenue for the treatment of kidney injury.
文摘BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment options.AIM To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic BTCs.METHODS This open-label,non-randomized,double-center,phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical University.Eligible patients were administered nab-paclitaxel(150 mg/m^(2),day 1)and capecitabine(2000 mg/m^(2),twice daily,days 1-7)in 14-day cycles until experiencing intolerable toxicity or disease progression.The primary outcome was the objective response rate(ORR).The secondary outcomes included the disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and safety.RESULTS A total of 44 patients successfully completed the trial,with a median age of 64.00 years(interquartile range,35.00-76.00),and 26(59.09%)were females.Tumor response assessment was impeded for one patient due to premature demise from tumor hemorrhage.Among the remaining 43 patients undergoing at least one imaging assessment,the ORR was 23.26%[95%confidence interval(CI):11.80%-38.60%],and the DCR was 69.77%(95%CI:53.90%-82.80%).The median OS was 14.1 months(95%CI:8.3-19.9),and the median PFS was 4.4 months(95%CI:2.5-6.3).A total of 41 patients(93.18%)experienced at least one adverse event(AE),with 10 patients(22.73%)encountering grade≥3 AEs,and the most frequent AEs of any grade were alopecia(79.50%),leukopenia(54.55%),neutropenia(52.27%),and liver dysfunction(40.91%),and no treatment-related deaths were documented.CONCLUSION Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.
文摘BACKGROUND The surgeon performing a distal gastrectomy,has an arsenal of reconstruction techniques at his disposal,Billroth II among them.Braun anastomosis performed during a Billroth II procedure has shown evidence of superiority over typical Billroth II,in terms of survival,with no impact on postoperative morbidity and mortality.AIM To compare Billroth II vs Billroth II and Braun following distal gastrectomy,regarding their postoperative course.METHODS Patients who underwent distal gastrectomy during 2002-2021,were separated into two groups,depending on the surgical technique used(Billroth II:74 patients and Billroth II and Braun:28 patients).The daily output of the nasogastric tube(NGT),the postoperative day that NGT was removed and the day the patient started per os feeding were recorded.Postoperative complications were at the same time noted.Data were then statistically analyzed.RESULTS There was difference in the mean NGT removal day and the mean start feeding day.Mean total postoperative NGT output was lower in Braun group(399.17 mL vs 1102.78 mL)and it was statistically significant(P<0.0001).Mean daily postoperative NGT output was also statistically significantly lower in Braun group.According to the postoperative follow up 40 patient experienced bile reflux and alkaline gastritis from the Billroth II group,while 9 patients who underwent Christodoulidis G et al.Billroth II and Braun compared with Billroth II WJM https://www.wjgnet.com 2 March 20,2024 Volume 14 Issue 1 Billroth II and Braun anastomosis were presented with the same conditions(P<0.05).CONCLUSION There was evidence of superiority of Billroth II and Braun vs typical Billroth II in terms of bile reflux,alkaline gastritis and NGT output.
基金Supported by Peking Union Medical College Hospital Deposit Integration Commission Funds(No.ZC201904168).
文摘AIM:To investigate the impacts of angiotensin II(Ang II)on retinal artery changes in apolipoprotein E deficient(apoE^(-/-))mice.METHODS:ApoE^(-/-)male mice were infused by minipumps with Ang II at 1000 ng/kg·min(Ang II group)or saline(control group)for 28d.They were underwent ophthalmic fundus examination on day 0,14,and 28 of infusion.Histopathologic examination,ribonucleic acid(RNA)sequencing and local Ang II measurement of retinas were conducted.RESULTS:Ophthalmic fundus examination showed Ang II infusion promoted the formation of retinal arterial aneurysm-like lesions on day 28.Optical coherence tomography revealed the ganglion cell and inner plexiform layer(GCIPL)thickness in the control group was significantly thinner than that in Ang II group(P<0.001).Hematoxylin-eosin staining demonstrated diffused swelling of GCIPL layer and its disordered structure in Ang II group.Transmission electron microscopy showed Ang II infusion caused aggravation of atherosclerotic lesions,including increased swelling,roughness,disorganization of the retinal vasculature,and vacuoles formation.RNA-sequencing and gene ontology enrichment analysis demonstrated that the structure and function of cellular membrane might be disturbed and visual function might be compromised by Ang II.The local level of Ang II was higher in Ang II infusion group but did not show significant differences compared to the control group(P=0.086).CONCLUSION:Ang II infusion promotes the formation of retinal arterial aneurysm-like lesions in apoE^(-/-)mice,causing aggravation of atherosclerotic lesions,more severe disorganization of the retinal vasculature and disturbance of the cellular membrane.
文摘Angiotensin II (Ang II) is the main mediator of the Renin-Angiotensin-System acting on AT<sub>1</sub> and other AT receptors. It is regarded as a pleiotropic agent that induces many actions, including functioning as a growth factor, and as a contractile hormone, among others. The aim of this work was to examine the impact of Ang II on the expression and function of α<sub>1</sub>-adrenergic receptors (α<sub>1</sub>-ARs) in cultured rat aorta, and aorta-derived smooth muscle cells. Isolated Wistar rat aorta was incubated for 24 h in DMEM at 37˚C, then subjected to isometric tension and to the action of added norepinephrine, in concentration-response curves. Ang II was added (1 × 10<sup>−5</sup> M), and in some experiments, 5-Methylurapidil (α<sub>1A</sub>-AR antagonist), AH11110A (α<sub>1B</sub>-AR antagonist), or BMY-7378 (α<sub>1D</sub>-AR antagonist), were used to identify the α<sub>1</sub>-AR involved in the response. Desensitization of the contractile response to norepinephrine was observed due to incubation time, and by the Ang II action. α<sub>1D</sub>-AR was protected from desensitization by BMY-7378;while RS-100329 and prazosin partially mitigated desensitization. In another set of experiments, isolated aorta-derived smooth muscle cells were exposed to Ang II and α<sub>1</sub>-ARs proteins were evaluated. α<sub>1D</sub>-AR increased at 30 and 60 min post Ang II exposure, the α<sub>1A</sub>-AR diminished from 1 to 4 h, while α<sub>1B</sub>-AR remained unchanged over 24 h of Ang II exposure. Ang II induced an increase of α<sub>1D</sub>-AR at short times, and BMY-7378 protected α<sub>1D</sub>-AR from desensitization.
基金National Key Research and Development Program,Grant/Award Number:2019YFA0903800,2021YFA0805701,2021YFA0805905 and 2022YFA1103603CAS Project for Young Scientists in Basic Research,Grant/Award Number:YSBR-012+2 种基金STI 2030-Major Project,Grant/Award Number:2023ZD0407503National Natural Science Foundation of China,Grant/Award Number:32071456 and 82241224Strategic Priority Research Program of the Chinese Academy of Sciences,Grant/Award Number:XDA16030000。
文摘Background:Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic,while immunogenic genes need to be eliminated to improve the immune compatibility between humans and pigs.Current knockout strategies are mainly aimed at the genes causing hyperacute immune rejection(HAR)that occurs in the first few hours while adaptive immune reactions orchestrated by CD4 T cell thereafter also cause graft failure,in which process the MHCⅡmolecule plays critical roles.Methods:Thus,we generate a 4-gene(GGTA1,CMAH,β4GalNT2,and CIITA)knockout pig by CRISPR/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions simultaneously.Results:We successfully obtained 4KO piglets with deficiency in all alleles of genes,and at cellular and tissue levels.Additionally,the safety of our animals after gene editing was verified by using whole-genome sequencing and karyotyping.Piglets have survived for more than one year in the barrier,and also survived for more than 3 months in the conventional environment,suggesting that the piglets without MHCⅡcan be raised in the barrier and then gradually mated in the conventional environment.Conclusions:4KO piglets have lower immunogenicity,are safe in genomic level,and are easier to breed than the model with both MHCⅠandⅡdeletion.