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.

Objective:To evaluate the clinical characteristics, pathology, treatment and prognosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in children.Methods:Clinical data (including gender, age of disease onset, affected sites, treatment, timing of allogeneic hematopoietic stem cell transplantation (allo-HSCT), etc.) of 7 children with BPDCN who were admitted to Beijing Children′s Hospital, Capital Medical University from December 2018 to December 2023 were analyzed retrospectively. Clinical outcomes were also assessed, with patients followed up until December 2024.Results:Among 7 patients, there were 3 males and 4 females. Age at disease onset ranged from 3.2 to 12.9 years. Initial presentations included subcutaneous nodules in 5 cases, rash in 1 case, and ankle pain in 1 case. Extra-cutaneous involvement was seen in the bone marrow, lymph nodes, and central nervous system. Six patients received induction chemotherapy using a modified lymphoblastic lymphoma regimen, 1 patient received the high-risk protocol for pediatric lymphoblastic lymphoma/leukemia and salvage therapy regimens. Allo-HSCT was performed soon after chemotherapy remission. The time to bridge allo-HSCT was 3.5 to 6.5 months. The follow-up time was 1.6 to 6.0 years. Six patients were in disease-free survival, while 1 patient survived with disease after recurrence following transplantation.Conclusions:BPDCN is rare in children and presents diverse clinical manifestations, with skin involvement being the predominant feature. Early allo-HSCT following complete remission with chemotherapy can improve prognosis.

Objective:To explore the feasibility and effect on the reconstruction of whole hand degloving injury by transfer of nerved tissue flaps in staged surgery.Methods:A retrospective study was conducted on the clinical data of 5 patients who suffered whole hand degloving injury and underwent staged reconstructive surgery with nerved tissue flaps, from December 2018 to December 2022 in the Department of Hand Surgery, Longgang Orthopaedics Hospital of Shenzhen. The patients were 4 males and 1 female, aged 22-45 years. Two of the whole-hand degloved injuries were left hands and 3 of right. Two patients had the whole-hand degloving injury combined with a fracture of distal phalangeal tuberosity, and 1 was complicated with partial rupture of the extensor tendon insertion. Areas of the whole hand degloving injury ranged from 215 cm 2 to 480 cm 2, the size of the hallux nail flaps for reconstruction of thumbs ranged from 54 cm 2 to 104 cm 2, the size of the hallux nail flaps for reconstruction of index fingers ranged from 65 cm 2 to 133 cm 2, and the size of the flaps for reconstruction of all the defects of hands ranged from 119 cm 2 to 255 cm 2. In primary surgery, the thumbs, index fingers and the first webs were reconstructed with bilateral hallux nail flaps to shape the appearance and gain the sensation function. Meanwhile, a single and large defect was created from the defects of hand by bundling up the middle, ring and little fingers together with the all the defects in both palmar and dorsal hand. Then an anterolateral thigh flap (ALTF) was used to have the created single defect wrapped together. Donor sites of the bilateral hallux nail flap were reconstructed with a lobulated ALTF from the other side or with bilateral peroneal artery perforator flaps. Donor sites of the ALTF and peroneal artery perforator flap were pulled and sutured. After the hallux nail flaps and ALTFs of the affected hands had survived and stabilised, multiple staged surgery were then carried out to firstly reconstruct the ring and little fingers, and followed by the middle and ring fingers in turns from the artificial syndactyly created in the primary surgery. In the final stage of surgery, skin of the radial side of middle and ring finger-pulps and the ulnar little finger-pulp were replaced by lateral toe flaps to reconstruct the sensations of the main sensory zones of middle, ring and little finger-pulps. Thereafter, the shape, TPD and finger extension and flexions were observed and evaluated through the postoperative follow-up, at the outpatient clinic according to the Evaluation Standard of Thumb and Finger Reconstruction Function of the Hand Surgery Society of the Chinese Medical Association. The appearance and function of the donor sites in both feet were evaluated with the Maryland foot score. Results:All flaps survived after surgery. Postoperative follow-up lasted up to 14 to 48 months after the last surgery. The appearance of fingers was satisfactory with good function. TPD of thumbs and index finger-pulps had achieved up to 6-8 mm, and 3-8 mm in the main sensory zones of middle, ring and little finger-pulps. TPD in the non-major sensory zones of middle, ring and little finger-pulps was found at 10-14 mm, which scored 13 to 14 and rated as excellent according to the Evaluation Standard of Thumb and Finger Reconstruction Function of the Hand Surgery Society of the Chinese Medical Association. Only a linear scar left in the donor site of thigh. As the appearance of the flaps on the feet was not bloated and there was no obvious abnormality in walking and running, therefore the function of feet scored up to 96 to 97 and rated excellent according to the Maryland foot score.Conclusion:A multi-staged reconstruction of a whole hand degloving injury with nerved tissue flaps not only achieves satisfactory digital and hand appearance, but also with good function. There is no obvious effect on the appearance and function of the donor sites. This surgical strategy is novel in the reconstruction of a whole hand degloving injury.

Objective:To develop a nomogram model for predicting the risk of ventilator-associated pneumonia (VAP) in patients with mechanical ventilation (MV) and to validate the stability of the prediction performance of the model.Methods:The patients with MV admitted to the Department of Critical Care Medicine of General Hospital of Ningxia Medical University from January 2019 to December 2022 were retrospectively selected according to the order of admission. The patients with MV were divided into the non-VAP group and the VAP group according to whether VAP occurred. The clinical data of the two groups, including general information, disease, medication, condition, and operation-related indicators were collected as candidate predictors of the model for comparison. Multivariate logistic stepwise forward regression analysis was used to screen the predictors that finally entered the model, and a nomogram model was constructed. The model discrimination was evaluated by the area under the receiver operating characteristic curve (AUC), the diagnostic test results of the model at the predicted threshold were calculated, the Hosmer-Lemeshow test was used to evaluate the model fit, and the Bootstrap resampling was used 1 000 times for internal validation, and model calibration and clinical applicability were evaluated by calibration curve and decision analysis curve, respectively.Results:A total of 1 250 patients with MV were included, including 1 102 patients in the non-VAP group and 148 patients in the VAP group, and the prevalence of VAP was 11.8%. The detection of multidrug-resistant organisms, chronic kidney disease, brain injury, oxygenation index, the place of tracheal intubation, reintubation, use of bronchoscopy, use of antibiotics, and MV duration were model predictors of VAP. The AUC of the nomogram model was 0.917 (95% CI: 0.895-0.939), the maximum Youden index of 0.697 corresponded to a prediction threshold of 0.096. The model accuracy, sensitivity and specificity were 0.836, 0.865, and 0.832, respectively. The positive predictive value and the negative predictive value were 0.409 and 0.979, respectively. The Hosmer- Lemeshow test indicated that the model fit well ( P=0.938). The results of the internal validation of the model showed that the predicted risk of the calibration curve was generally consistent with the actual risk, and the decision threshold probability of the decision analysis curve ranged from 2% to 90%. Conclusions:The nomogram model developed in this study is simple, convenient and has relatively stable prediction performance, which can be externally validated to evaluate the extrapolation of the model, and provide a basis for individualized clinical prediction of the risk of VAP in patients with MV.

Objective To describe and evaluate the clinical studies of postoperative pain sensitization caused by sleep deprivation through the evidence map system,understand the distribution of evidence in this field,and provide reference for subsequent evidence research.Methods A computer-based search of PubMed,EMBASE,Cochrane library,Web of Science,CNKI,Wanfang Data,VIP and Chinese Biomedical Literature Database from inception to August 2023 was conducted to obtain intervent ion studies,observational studies and systematic reviews/Meta-analysis of postoperative pain sensitization caused by sleep deprivation.The research characteristics and methodological quality were analyzed and evaluated.The Cochrane Handbook for Systematic Reviews,the Newcastle-Ottawa Scale(NOS)and the AMSTAR-2 scale were used to evaluate the quality of the included studies,and the evidence was comprehensively analyzed and displayed by means of bubble chart,table and text.Results A total of 35 observational studies(31 cohort studies and 4 case-control studies),15 randomized controlled trials and 4 systematic reviews/Meta-analyses were included.The number of publications increased rapidly after 2018 and peaked in 2022,and clinical studies in this field mainly fo-cused on cohort studies,with fewer randomized controlled trials and systematic reviews/Meta-analysis studies.The results of the evidence map showed that in terms of quality,22 studies were'high quality',24 studies were'medium quality',and 8 studies were'low quality'.Thirty studies showed that sleep deprivation could induce postoperative pain sensitization.Only 2 studies suggested that sleep disorders were not significantly asso-ciated with postoperative pain sensitization,and ten studies were uncertain whether sleep deprivation could in-duce postoperative pain sensitization.Conclusions Overall evidence shows that sleep deprivation can induce postoperative pain sensitization,but the evaluation dimensions are limited and the methodological quality of the included literature needs to be improved.More high-quality,large-sample and standardized clinical studies should be carried out in the future to provide better scientific basis for clinical work.

Objective To investigate the expression characteristics and clinical diagnostic value of programmed death receptor 1(PD-1)and its corresponding ligand(PD-L1)in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods One hundred and sixty COPD patients who visited Dongzhimen Hospital of Beijing University of Chinese Medicine from April 2024 to November 2024 were included and divided into an acute exacerbation group of 100 cases and a stable group of 60 cases according to the severity of the disease.Additionally,40 healthy volunteers during the same period were recruited as the control group.The general clinical data of the patients were collected.Chronic Obstructive Pulmonary Disease Assessment Test(CAT)and Modified Medical Research Council Dyspnea Questionnaire(mMRC)Scale were used to test the severity of the disease;respiratory function testing was performed and fasting venous blood was collected for serum PD-1 and PD-L1 testing.Pearson correlation was used to analyze the correlation between serum PD-1,PD-L1,CAT,and mMRC,and multiple logistic regression analysis to identify the influencing factors of AECOPD.Receiver operating characteristic(ROC)curve was drawn to evaluate the diagnostic value of serum PD-1 and PD-L1 level for AECOPD.Results Serum PD-1 level in the stable COPD group and AECOPD group was significantly increased compared with that in the control group,while serum PD-L1 level was significantly decreased,showing statistical significance(P<0.05);The level of PD-1 gradually increased with the grading of lung function and the deterioration of AECOPD,with statistical significance(P<0.05);Pearson correlation showed that serum PD-1 level was positively correlated with CAT scores in COPD patients,while negatively with CAT scores,showing statistical significance(P<0.05);Multiple logistic regression analysis showed that elevated levels of serum inter-leukin-6(IL-6),neutrophil to lymphocyte ratio(NLR),and PD-1 were risk factors for AECOPD,while elevated level of PD-L1 was protective factor for AECOPD(P<0.05);ROC curve showed that the levels of PD-1,PD-L1,IL-6,NLR,and the area under the ROC curve(AUC)for their combined prediction of AECOPD diagnosis were 0.884,0.867,0.868,0.802,and 0.995,respectively.Conclusion Serum PD-1 and PD-L1 in AECOPD patients have presented certain expression characteristics,with elevated PD-1 level while decreased PD-L1 level.Both have good clinical diagnostic value for AECOPD.

This study aimed to investigate the effects of sweet potato leaf extract on production per-formance,systematic and mammary gland oxidative stress status and rumen microbiota of dairy goats fed high concentrate diets.Twenty Guanzhong dairy goats with same parity,similar lactation period(120±15)d and healthy body condition were selected and randomly divided into four groups:low-concentrate(LC),low-concentrate supplemented with 1％sweet potato leaf extract(LCS),high-concentrate(HC)and high-concentrate supplemented with 1％sweet potato leaf ex-tract(HCS).The experimental period was 35 days.The results showed that in the third week,milk yield in the HCS group was significantly higher than that in the LC and LCS groups(P＜0.05).The content of lipopolysaccharide in the rumen fluid of the HC group was significantly higher than that of the other three groups(P＜0.05),the content of malondialdehyde in the serum of the HC group was significantly higher than that of the LCS group(P＜0.05),the content of reactive oxygen species,protein carbonyl,8-hydroxydeoxyguanosine in the milk of the HC group was sig-nificantly higher than that of the LC and LCS groups(P＜0.05),GSH-Px in HCS group was sig-nificantly higher than that in the other three groups(P＜0.05).After the addition of sweet potato leaf extract,there was an increasing trend in the content of Anabaena phylum at the phylum level.In the joint analysis of genera,rumen fluid LPS showed highly significant negative correlation with Succiniclasticum(P＜0.01)and negative correlation with Prevotella(P＜0.05).Valeric acid was negatively correlated with Prevotella(P＜0.05).The pH value was negatively correlated with Treponema(P＜0.05).Butyric acid was positively correlated with Anaeroplasma(P＜0.05).In conclusion,the addition of sweet potato leaf extract to the diet can increase milk production and al-leviate the state of mammary gland oxidative stress,as well as improving rumen microbial diversi-ty of dairy goats.

Objective To evaluate the application of high-resolution magnetic resonance vessel wall imaging(HRMR-VWI)in identifying high-risk features of intracranial atherosclerotic plaques,and to analyze the correlation between plaque characteristics and stroke recurrence under varying degrees of stenosis.Methods The data from 368 patients with intracranial atherosclerotic stenosis(ICAS)across two centers were retrospectively analyzed.Based on the degree of stenosis,all patients were categorized into mild-to-moderate stenosis group(luminal stenosis<70%,n=155)and severe stenosis group(luminal stenosis≥70%,n=213).HRMR-VWI images and clinical information of the patients were collected and analyzed,and the culprit plaques were quantitatively analyzed.Univariate and multivariate logistic regression analyses were employed to identify the risk factors for stroke recurrence,and the predictive performance was evaluated using the area under the curve(AUC)of the receiver operating characteristic(ROC)curve.Results Higher normalized wall index(NWI)[odds ratio(OR)=1.082,95%confidence interval(CI)1.050-1.118,P<0.05]and the presence of intraplaque hemorrhage(IPH)(OR=1.843,95%CI 1.120-3.036,P<0.05)were risk factors for stroke recurrence in all patients.And these two factors were also significant in the mild-to-moderate stenosis group(NWI:OR=1.088,95%CI 1.009-1.186,P<0.05;IPH:OR=4.049,95%CI 1.227-16.065,P<0.05).A predictive model for stroke recurrence was constructed using the combination of IPH and NWI,with the best performance in the mild-to-moderate stenosis group(AUC=0.813,95%CI 0.723-0.906).Conclusion In patients with luminal stenosis<70%,the increase of NWI and the presence of IPH have been validated as significant and effective indicators for predicting stroke recurrence,demonstrating notable predictive performance.In contrast,among patients with luminal stenosis≥70%,the utility of plaque characteristics in predicting stroke recurrence is relatively lower,indicating that the correlation between plaque characteristics and stroke recurrence varies across different degrees of stenosis.

This study aimed to investigate the effects of sweet potato leaf extract on production per-formance,systematic and mammary gland oxidative stress status and rumen microbiota of dairy goats fed high concentrate diets.Twenty Guanzhong dairy goats with same parity,similar lactation period(120±15)d and healthy body condition were selected and randomly divided into four groups:low-concentrate(LC),low-concentrate supplemented with 1％sweet potato leaf extract(LCS),high-concentrate(HC)and high-concentrate supplemented with 1％sweet potato leaf ex-tract(HCS).The experimental period was 35 days.The results showed that in the third week,milk yield in the HCS group was significantly higher than that in the LC and LCS groups(P＜0.05).The content of lipopolysaccharide in the rumen fluid of the HC group was significantly higher than that of the other three groups(P＜0.05),the content of malondialdehyde in the serum of the HC group was significantly higher than that of the LCS group(P＜0.05),the content of reactive oxygen species,protein carbonyl,8-hydroxydeoxyguanosine in the milk of the HC group was sig-nificantly higher than that of the LC and LCS groups(P＜0.05),GSH-Px in HCS group was sig-nificantly higher than that in the other three groups(P＜0.05).After the addition of sweet potato leaf extract,there was an increasing trend in the content of Anabaena phylum at the phylum level.In the joint analysis of genera,rumen fluid LPS showed highly significant negative correlation with Succiniclasticum(P＜0.01)and negative correlation with Prevotella(P＜0.05).Valeric acid was negatively correlated with Prevotella(P＜0.05).The pH value was negatively correlated with Treponema(P＜0.05).Butyric acid was positively correlated with Anaeroplasma(P＜0.05).In conclusion,the addition of sweet potato leaf extract to the diet can increase milk production and al-leviate the state of mammary gland oxidative stress,as well as improving rumen microbial diversi-ty of dairy goats.

Objective To investigate the expression characteristics and clinical diagnostic value of programmed death receptor 1(PD-1)and its corresponding ligand(PD-L1)in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods One hundred and sixty COPD patients who visited Dongzhimen Hospital of Beijing University of Chinese Medicine from April 2024 to November 2024 were included and divided into an acute exacerbation group of 100 cases and a stable group of 60 cases according to the severity of the disease.Additionally,40 healthy volunteers during the same period were recruited as the control group.The general clinical data of the patients were collected.Chronic Obstructive Pulmonary Disease Assessment Test(CAT)and Modified Medical Research Council Dyspnea Questionnaire(mMRC)Scale were used to test the severity of the disease;respiratory function testing was performed and fasting venous blood was collected for serum PD-1 and PD-L1 testing.Pearson correlation was used to analyze the correlation between serum PD-1,PD-L1,CAT,and mMRC,and multiple logistic regression analysis to identify the influencing factors of AECOPD.Receiver operating characteristic(ROC)curve was drawn to evaluate the diagnostic value of serum PD-1 and PD-L1 level for AECOPD.Results Serum PD-1 level in the stable COPD group and AECOPD group was significantly increased compared with that in the control group,while serum PD-L1 level was significantly decreased,showing statistical significance(P<0.05);The level of PD-1 gradually increased with the grading of lung function and the deterioration of AECOPD,with statistical significance(P<0.05);Pearson correlation showed that serum PD-1 level was positively correlated with CAT scores in COPD patients,while negatively with CAT scores,showing statistical significance(P<0.05);Multiple logistic regression analysis showed that elevated levels of serum inter-leukin-6(IL-6),neutrophil to lymphocyte ratio(NLR),and PD-1 were risk factors for AECOPD,while elevated level of PD-L1 was protective factor for AECOPD(P<0.05);ROC curve showed that the levels of PD-1,PD-L1,IL-6,NLR,and the area under the ROC curve(AUC)for their combined prediction of AECOPD diagnosis were 0.884,0.867,0.868,0.802,and 0.995,respectively.Conclusion Serum PD-1 and PD-L1 in AECOPD patients have presented certain expression characteristics,with elevated PD-1 level while decreased PD-L1 level.Both have good clinical diagnostic value for AECOPD.