The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.

Background In recent years,rare diseases have become a major public health issue.There is an urgent need to improve the diagnosis and treatment for these diseases,and the training for doctors engaged in rare diseases is an important part of it.Methods This study conducted a questionnaire survey on the doctors engaged in rare diseases in Peking Union Medical College Hospital to better understand their characteristics and evaluate their psychological and working status.Results A total of 95 questionnaires from doctors engaged in rare diseases were collected in this study,among which the female:male ratio was 1.6∶1,and 63.2％of them were in the 40-54 age group.Their main reason for choosing rare diseases was the enjoyment in the process of studying rare diseases(64.2％).Compared with the 108 doctors not engaged in rare diseases surveyed during the same period,those working on rare diseases reported higher patient recognition based on self-evaluation(P＜0.001).In terms of the time-consuming work,in addition to routine medical work,teaching and research,34.7％of doctors engaged in rare diseases chose doctor-patient communication and 31.6％chose medical man-agement communication.Conclusions This study proposes some suggestions on the talent training for rare dis-eases,the establishment of continuing education platforms,and the technology and policy support needed through the analysis of the questionnaire survey results of doctors engaged in rare diseases.

Objective:To explore the surgical procedure and clinical effect of the free Flow-through superficial peroneal artery flap for repairing the digit injury with defect of proper palmar digital artery.Methods:From June, 2015 to December, 2019, free Flow-through superficial peroneal artery flap was used to repair the digit injury and to bridge the proper digital artery in 7 digits of 7 patients. There were 2 thumbs, 3 index fingers and 2 middle fingers. The size of defects on digits ranged from 2.5 cm×3.0 cm to 5.0 cm×7.0 cm. The defects of digit proper artery were 1.0 to 3.0 cm. The size of flaps was from 3.0 cm×3.5 cm to 5.5 cm×8.0 cm. The donor areas of the flap were directly sutured or covered with skin graft. Postoperative supportive treatments were given, such as infection prevention, antispasmodic, anticoagulant, analgesia and fluid infusion. The patients were kept in bed for 1 week after surgery. Monthly follow-up review were conducted and the patients were kept with the rehabilitation exercises under medical guidance.Results:All the patients entered postoperative followed-up for 6 to 18 months, with an average of 8 months. All flaps survived without any adverse event. All wounds achieved stage-one-healing. The flaps appeared in good colour, texture, elasticity and the plumps of the digit without obvious bloating. There was no obvious swelling and atrophy of the digits. The skin temperature was normal. According to the Standard for Evaluation of Upper Limb Function by the Hand Surgery Society of Chinese Medical Association, 3 digits were excellent and 4 were good. There was no obvious scar at the donor site of shank. The donor site had a good appearance and the limb function was not affected.Conclusion:The free Flow-through superficial peroneal artery flap is an ideal material to repair the defect of digit with the defect of proper digital artery. It has the advantages of simple surgical procedure, reliable blood supply and satisfactory appearance. The defect of proper digit artery can be repaired at the same time of the surgical procedure. The blood supply, appearance and function of the digits could be well recovered and the donor site is not affected.

Objective To investigate the common initial clinical presentations of primary Sj(o)gren's syndrome (pSS) with pulmonary complications,and to explore the differences between patients with extraglandular manifestations at disease onset (EGM) and those with glandular manifestations at disease onset (GM).Methods A total of 1 341 hospitalized SS patients from 2003 to 2012 were retrospectively reviewed.Of them,102 hospitalized patients with pSS'associated lung disease were analyzed and included.Case control study was performed to explore the differences between the EGM group and the GM group.Results Fifty-one percent of patients were presented with EGM at onset,with significantly shorter disease duration [36 (12,156) m vs 102 (48,159) m,x2=-2.41,P=0.016].Although the mean diagnose time was similiar,only 4％ of the EGM group could be confirmed the pSS diagnose at onset,which was significantly less frequently than that of the GM group (34％,22=15.29,P＜0.01).Case control study revealed that hyperglobulinemia,elevated RF titers and anti-SSA and/or anti-SSB test positive were less predominant in the EGM group [IgG 16(12,21) g/L vs 21 (15,28) g/L,x2=-2.15,P=0.032;22 (20,171) U/ml vs 104 (20,238) U/ml,x2=-l.98,P=0.048;33％ vs 72％,x2=15.78,P＜0.01].The predicted value of TLC and FVC were lower [(87±23)％ vs (97±20)％,x2=-1.96,P=0.050;(8±28)％ vs (100±27)％,x2=-1.70,P=0.089] and HRCT score was higher in EMG group [12(88,15) vs 8(5,13),x2=-1.82,P=0.070].Conclusion EMG at onset is the common initial manifestation of pSS'associated lung involvement.Pulmonary complication is more progressively and severe than those with MG at onset.Anti'SSA positive,elevated RF titer and hyperglobulinemia are not predominant for patients with EMG at onset.

OBJECTIVE: To evaluate the value of super-elective transcatheter external carotid arterial embolization (TAE) in the treatment of intractable epistaxis. METHOD: Forty-six cases of intractable epistaxis were selected, TAE was performed in 36 cases and externa carotid artery ligation was elected in 10 cases. RESULT: The curing rate was 88.9% (32/36) in cases treated by TAE and was 40.0% (4/10) in cased treated by external carotid artery ligation, and the average hospital days of the former was 4.8 days, while the latter was 10 days. Recurrency were effectively stopped bleeding by all kinds of methods, and complications were rare. CONCLUSION Transcatheter external carotid arterial embolization is a simple, safe and effective treatment for the intractable epistaxis, which has more advantages than external carotid artery ligation, and comprehensive methods can effectively and thoroughly cure intractable epistaxis.
Adult ; Aged ; Carotid Artery, External ; Embolization, Therapeutic ; methods ; Epistaxis ; therapy ; Female ; Humans ; Male ; Middle Aged ; Treatment Outcome

Objective:To assess incidence of malnutrition and malnutrition risk of six department patients.Methods:The information of 1 200 patients were collected,200 in each of 6 departments in our hospital.Nutrition status was assessed according to Nutrition Risk Screening(NRS)published by ESPEN in 2001.Results:The incidence of malnutrition and malnutrition risk varied from 7.5% to 59% and 36% to 72% respectively in different department.Conclusion:The incidence of malnutrition is closely related to the kind and severity of the disease.It is nessissary to assess the nutrition status of high risk patients in time.NRS can be used simply and fastly in most inhospital patients.

Objective: To improve the traditional preparation procedure of effervescent tablets in order to raise stabilization. Methods: The orthogonal design was used for improvement of process. Results: The optimum procedure condition was A 3B 2C 1. That is adding 7.5% citric acid, 11.25% sodium bicarbonate encapsulated by 5% PEG. Conclusion: The new procedure is superior to the traditional procedure, and it is suitable for the requirement of production on a large scale.