Parkinson's disease(PD)is one of the most common neurodegenerative disorders.Recent evidence implicates pyroptosis as one of the pathogenic mechanisms in central nervous system disorders,although its specific mechanisms remain unclear.In this study,SH-SY5Y cells were transfected with py-roptosis-related proteins GSDME full-length(GSDME-F)or GSDME-N terminal(GSDME-N)plasmids revealed that GSDME-N significantly reduced mitochondrial membrane potential(P＜0.0001).To inves-tigate the mechanism by which GSDME mediates mitochondrial dysfunction,Western blotting analysis demonstrated that transfection with GSDME-N plasmids significantly increased BAX expression and en-hanced its translocation to mitochondria in both HEK 293T and SH-SY5Y cells(P＜0.05).SH-SY5Y cells treated with varying concentrations of rotenone(ROT)exhibited GSDME cleavage,elevated BAX expression(P＜0.05),increased mitochondrial BAX aggregation(P＜0.05),and reduced mitochondrial membrane potential(P＜0.01),as confirmed by Western blotting and JC-1 staining.Concurrently,MTT assays assessing cell viability and lactate dehydrogenase(LDH)release assays indicated that ROT in-duced these processes prior to pyroptosis.Furthermore,in a ROT-induced mouse PD model,ROT trig-gered GSDME cleavage,enhanced BAX expression,caused dopaminergic neuronal damage,and induced motor deficits.In summary,this study demonstrates that GSDME-N exacerbates mitochondrial damage and increases cytotoxicity by upregulating BAX expression and facilitating its mitochondrial translocation.This study provides novel insights into the role of GSDME in PD pathogenesis and suggests potential avenues for therapeutic intervention.

Objective To investigate the feasibility and safety of transoral transgastric natural orifice transluminal endoscopic surgery(TG-NOTES)cholecystectomy in miniature pigs.Methods A total of 11 miniature pigs were selected as the experimental subjects and underwent TG-NOTES cholecystectomy.These pigs were divided into the Group A and Group B according to the surgical procedures.Among them,7 miniature pigs in the Group A underwent endoscopic cholecystectomy without dissecting the gallbladder triangle,while 4 miniature pigs in the Group B underwent endoscopic cholecystectomy after dissecting the gallbladder triangle.The success rate of surgery,the time of each stage of surgery,the incidence of complications,the success rate of cholecystectomy and the survival rate of miniature pigs in the two groups were counted.One miniature pig in the Group A and 4 miniature pigs in the Group B were selected for survival experiments.After surviving for 1 week,they were killed and dissected to observe the healing of incision and incidence of complications.Results The surgical survival rate of experimental animals was 100%,and the success rate of cholecystectomy was 100%.There was no significant difference in the surgical time,time of cut the stomach into the abdomen,time of gallbladder exploration or time of gallbladder removal of miniature pigs between the two groups(P>0.05).The time of ligating gallbladder artery of miniature pigs in the Group B was longer than that in the Group A,and the time of isdating gallbladder was shorter than that in the Group A,with statistically significant differences(P<0.05).There was no significant difference in the average number of complications of miniature pigs between the two groups(P>0.05).The dissection of animals after survival experiments revealed that the incisions healed well without serious complications.Conclusion This study successfully establishes the surgical model of TG-NOTES cholecystectomy,and confirms the safety and feasibility of TG-NOTES cholecystectomy.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans ; Calcium Compounds/therapeutic use* ; Consensus ; Dental Pulp ; Dentition, Permanent ; Oxides/therapeutic use* ; Pulpitis/therapy* ; Pulpotomy/standards*

Objective To evaluate the diagnostic value of transrectal contrast-enhanced ultrasound (CEUS) for rectal cancer with intestinal stenosis caused by tumors. Methods Forty-nine patients with rectal cancer underwent transrectal CEUS and magnetic resonance imaging (MRI) before surgery.Intraoperative tumor localization and postoperative pathological results were taken as the gold standard for diagnosis.The differences in T stage,localization,and tumor length of rectal cancer were compared between the two methods. Results The total accuracy rates of transrectal CEUS and MRI in diagnosing T stage were 75.5% (36/49) and 67.3% (33/49),which had no significant difference (χ²=0.8,P=0.371).The total accuracy rates of transrectal CEUS and MRI in judging tumor localization were 79.5% (39/49) and 77.5% (38/49),which had no significant difference (χ²=0.061,P=0.806).The measurement results of tumor length in pathological examination had no significant difference from the transrectal CEUS results (t=1.42,P=0.162) but a significant difference from the MRI results (t=3.38,P=0.001).Furthermore,transrectal CEUS detected 8 (16.3%) cases of colonic polyps among the 49 patients,while MRI did not detect colon lesions. Conclusions Transrectal CEUS has good consistency with MRI in T staging and localization judgement of rectal cancer with intestinal stenosis,and this method can more accurately evaluate the tumor length and simultaneously evaluate whether there is a lesion in the entire colon at the proximal end of stenosis.It can be used as a supplementary examination before rectal cancer treatment in clinical practice.
Humans ; Rectal Neoplasms/complications* ; Male ; Middle Aged ; Female ; Aged ; Contrast Media ; Ultrasonography ; Adult ; Magnetic Resonance Imaging ; Constriction, Pathologic/diagnostic imaging* ; Aged, 80 and over ; Intestinal Obstruction/etiology*

Objective To identify the pathogenic gene and variant for a family with branchio-otic syndrome.Methods The clinical data of this family were collected,and the peripheral blood was extracted for deafness gene NGS panel analysis.Pathogenic variation detected was verified by Sanger sequencing.Results The family contained 17 members in three-generations,3 of whom exhibited autosomal dominant,hearing loss,preauricular fistula and branchial cleft fistula,which were in accordance with the clinical diagnosis criteria of branchio-otic syndrome.A no-vel heterozygous variant c.963dupT(p.E322X)in EYA1 gene was identified,which co-segregated with the branchi-o-otic syndrome phenotype in the family.The variant was a nonsense variant resulting in the premature appearance of the stop codon.According to the American College of Medical Genetics and Genomics(ACMG)guidelines and the criteria,the variant was classified as pathogenic.Conclusion We identified a novel pathogenic variant EYA1:c.963dupT(p.E322X)in a family with branchio-otic syndrome.

Objective To investigate the feasibility and safety of transoral transgastric natural orifice transluminal endoscopic surgery(TG-NOTES)cholecystectomy in miniature pigs.Methods A total of 11 miniature pigs were selected as the experimental subjects and underwent TG-NOTES cholecystectomy.These pigs were divided into the Group A and Group B according to the surgical procedures.Among them,7 miniature pigs in the Group A underwent endoscopic cholecystectomy without dissecting the gallbladder triangle,while 4 miniature pigs in the Group B underwent endoscopic cholecystectomy after dissecting the gallbladder triangle.The success rate of surgery,the time of each stage of surgery,the incidence of complications,the success rate of cholecystectomy and the survival rate of miniature pigs in the two groups were counted.One miniature pig in the Group A and 4 miniature pigs in the Group B were selected for survival experiments.After surviving for 1 week,they were killed and dissected to observe the healing of incision and incidence of complications.Results The surgical survival rate of experimental animals was 100%,and the success rate of cholecystectomy was 100%.There was no significant difference in the surgical time,time of cut the stomach into the abdomen,time of gallbladder exploration or time of gallbladder removal of miniature pigs between the two groups(P>0.05).The time of ligating gallbladder artery of miniature pigs in the Group B was longer than that in the Group A,and the time of isdating gallbladder was shorter than that in the Group A,with statistically significant differences(P<0.05).There was no significant difference in the average number of complications of miniature pigs between the two groups(P>0.05).The dissection of animals after survival experiments revealed that the incisions healed well without serious complications.Conclusion This study successfully establishes the surgical model of TG-NOTES cholecystectomy,and confirms the safety and feasibility of TG-NOTES cholecystectomy.

Objective To identify the pathogenic gene and variant for a family with branchio-otic syndrome.Methods The clinical data of this family were collected,and the peripheral blood was extracted for deafness gene NGS panel analysis.Pathogenic variation detected was verified by Sanger sequencing.Results The family contained 17 members in three-generations,3 of whom exhibited autosomal dominant,hearing loss,preauricular fistula and branchial cleft fistula,which were in accordance with the clinical diagnosis criteria of branchio-otic syndrome.A no-vel heterozygous variant c.963dupT(p.E322X)in EYA1 gene was identified,which co-segregated with the branchi-o-otic syndrome phenotype in the family.The variant was a nonsense variant resulting in the premature appearance of the stop codon.According to the American College of Medical Genetics and Genomics(ACMG)guidelines and the criteria,the variant was classified as pathogenic.Conclusion We identified a novel pathogenic variant EYA1:c.963dupT(p.E322X)in a family with branchio-otic syndrome.

Parkinson's disease(PD)is one of the most common neurodegenerative disorders.Recent evidence implicates pyroptosis as one of the pathogenic mechanisms in central nervous system disorders,although its specific mechanisms remain unclear.In this study,SH-SY5Y cells were transfected with py-roptosis-related proteins GSDME full-length(GSDME-F)or GSDME-N terminal(GSDME-N)plasmids revealed that GSDME-N significantly reduced mitochondrial membrane potential(P＜0.0001).To inves-tigate the mechanism by which GSDME mediates mitochondrial dysfunction,Western blotting analysis demonstrated that transfection with GSDME-N plasmids significantly increased BAX expression and en-hanced its translocation to mitochondria in both HEK 293T and SH-SY5Y cells(P＜0.05).SH-SY5Y cells treated with varying concentrations of rotenone(ROT)exhibited GSDME cleavage,elevated BAX expression(P＜0.05),increased mitochondrial BAX aggregation(P＜0.05),and reduced mitochondrial membrane potential(P＜0.01),as confirmed by Western blotting and JC-1 staining.Concurrently,MTT assays assessing cell viability and lactate dehydrogenase(LDH)release assays indicated that ROT in-duced these processes prior to pyroptosis.Furthermore,in a ROT-induced mouse PD model,ROT trig-gered GSDME cleavage,enhanced BAX expression,caused dopaminergic neuronal damage,and induced motor deficits.In summary,this study demonstrates that GSDME-N exacerbates mitochondrial damage and increases cytotoxicity by upregulating BAX expression and facilitating its mitochondrial translocation.This study provides novel insights into the role of GSDME in PD pathogenesis and suggests potential avenues for therapeutic intervention.