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 explore the risk factors for central line-associated bloodstream infection(CLABSI)in the maintenance hemodialysis(MHD)patients based on the informatization surveillance system and establish and verify the risk prediction model so as to provide bases for early identification and prevention of CLABSI.METHODS A total of 300 MHD patients who were treated in hemodialysis center of the Affiliated Hospital of Xuzhou Medical University from Jan.2020 to Dec.2023 were recruited as the research subjects and were randomly divided into the training set group with 210 cases and the validation set group with 90 cases in a 7∶3 ratio.The risk factors for the CLABSI were analyzed,the prediction model was established and verified.The performance of the model was evaluated by the area under the curve(AUC)of receiver operating characteristic(ROC)curves and Hosmer-Lemeshow goodness of fit test.RESULTS Among the 300 MHD patients who were treated with central venous catheters,32 were diagnosed with CLABSI,and the incidence was 0.65 per 1,000 catheter days.Multivari-ate analysis showed that catheter indwelling time,repeated catheterization,previous history of catheter-related in-fection and diabetes mellitus were the risk factors for the CLABSI in the MHD patients(P＜0.05).The model based on the logistic regression equation was established as follows:logit(P)=-5.661+0.024 × catheter in-dwelling duration(week)+2.037 × repeated catheterization+1.546 × previous history of catheter-related infec-tion+3.391× diabetes mellitus.ROC curve analysis showed that the AUC of the training set was 0.916(95％CI:0.837 to 0.994),with the sensitivity 87.00％,the specificity 86.63％,Youden index 0.736;the AUC of the vali-dation set was 0.797(95％CI:0.632 to 0.962),with the sensitivity 77.78％,the specificity 82.72％,the Youden index 0.605.The model showed excellent discrimination and calibration degree.CONCLUSION The logistic regres-sion equation that is established based on the 4 risk factors,catheter indwelling duration,repeated catheterization,previous history of catheter-related infection and diabetes mellitus,shows remarkable predictive efficiency,and it can provide evidence for clinical screening and prevention of CLABSI.

Objective To construct a knowledge graph of healthcare-associated infection(HAI)prevention and control course,and evaluate its usability.Methods Based on the constructivist learning theory and the analyze-de-sign-develop-implement-evaluate(ADDIE)model,knowledge from various sources such as books,guidelines,and literature related to HAI prevention and control were integrated.The knowledge graph of HAI prevention and con-trol course were designed and constructed with the support of knowledge graph technology in Chaoxing Fanya plat-form.Thirty medical students were selected by convenience sampling method to try out the course knowledge graph.System usability scale and usage effect questionnaire were filled out to evaluate the usability of the knowledge graph.Results The knowledge graph of HAI prevention and control course contained 379 knowledge points asso-ciated with 520 test questions and 56 learning resources.After testing,the total score([70.50±12.20]points)was obtained for the usability of the knowledge graph.Among the four dimensions of the usage effect agreement ques-tionnaire,satisfaction,learning attitude,learning ability,and learning resource support accounted for 93.33％-96.67％,90.00％,93.33％-96.67％,and 83.33％-90.00％,respectively,with a high overall satisfaction rate.Conclusion The knowledge graph of HAI prevention and control course has good usability,which can realize students'personalized independent learning and improve their learning efficiency.

ObjectiveThis study aimed to investigate the intervention effect of Renqing Mangjue on the malignant transformation of gastric mucosal epithelial cells induced by N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） and to explore its molecular mechanism in preventing precancerous lesions of gastric cancer based on the cyclic guanosine monophosphate （cGMP）/protein kinase G （PKG）/mitogen-activated protein kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway. MethodsHuman gastric mucosal epithelial cells （GES-1） were initially induced by MNNG to establish a precancerous cell model （MC cells）. The effective concentration of MNNG for inducing malignant transformation in GES-1 cells was screened using the cell proliferation activity decection （CCK-8） assay， and the effective concentration of Renqing Mangjue for inhibiting the proliferation of transformed GES-1 cells was also determined. GES-1 cells were divided into a blank control group， a model group， and treatment groups with Renqing Mangjue at concentrations of 1， 3， 10， and 30 mg·L^-1. Furthermore， the effects of Renqing Mangjue on the migratory ability and epithelial-mesenchymal transition （EMT） characteristics of GES-1 malignant transformed cells were evaluated using Transwell migration assays， wound healing assays， and real-time quantitative reverse transcription polymerase chain reaction （Real-time PCR）. Additionally， candidate chemical components and target sites of Renqing Mangjue were obtained from the TCMIP v2.0 database， and disease targets at various stages of gastric cancer precursors were sourced from the Gene Expression Omnibus （GEO） database. Pathway enrichment analysis was performed using the Metascape database to predict the potential mechanisms of action of Renqing Mangjue. Finally， the protective mechanism of Renqing Mangjue against gastric cancer precursors was validated through Western blot analysis. ResultsAt a concentration of 20 μmol·L^-1， MNNG exhibited an inhibition rate of approximately 50% on GES-1 cells （P<0.01）， and at this concentration， the GES-1 cells displayed biological characteristics indicative of malignant transformation. In contrast， Renqing Mangjue had no significant effect on the proliferation of normal GES-1 cells， but significantly inhibited the proliferation of MC cells （P<0.01） and markedly reduced their migratory capacity （P<0.01）. Moreover， it also increased the mRNA expression level of E-cadherin during the EMT process （P<0.05）， while inhibiting the expression of both N-cadherin and the transcription factor Snail mRNA （P<0.05， P<0.01）. Network predictions suggested that Renqing Mangjue may prevent gastric cancer precursors through modulating the cGMP/PKG and MAPK/ERK signaling pathways. Furthermore， Western blot results indicated that Renqing Mangjue upregulated the expression of PKG and NPRB （B-type natriuretic peptide receptor） proteins in the cGMP/PKG pathway （P<0.01）， while downregulating the expression of the downstream proteins MEK and ERK （P<0.05， P<0.01）. ConclusionIn summary， Renqing Mangjue can prevent gastric cancer precursors by inhibiting the proliferation and migration of malignant transformed GES-1 cells， thereby delaying the EMT process. The underlying mechanisms may be related to the activation of the cGMP/PKG pathway and the inhibition of the MEK/ERK signaling pathway.

To address the common clinical problems associated with warm needling moxibustion, such as burns, bending of needle handles, and the inability to perform moxibustion during oblique needling, an adjustable warm needling moxibustion device is designed and has been granted a national patent. This device consists of five components: a moxa cylinder, an adjustable arm, a supporting tube, a temperature alarm, and a fixing strap. It allows infrared heat radiation from the moxa to pass through while blocking falling ash, thereby ensuring therapeutic efficacy and preventing burns. The device accommodates both perpendicular and oblique needling angles and adapts to various body positions, effectively avoiding deformation of the needle handle. It is easy to operate and offers high safety.
Moxibustion/methods* ; Humans ; Equipment Design ; Needles

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 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 evaluate the clinical efficacy and feasibility of the reversed fascial pedicled island flap with supercharged venous drainage in reconstruction of finger pulp defects.Methods:A retrospective study was conducted between June 2021 and October 2024 at the Department of Hand Surgery, the Eighth People's Hospital of Longgang District of Shenzhen, to evaluate 76 patients (76 digits) who had finger pulp defects and were treated by the reversed fascial pedicled island flap incorporating supercharged venous drainage. The patients were 62 males and 14 females, aged 12-66 (mean 29) years. All patients presented with pulp defects only (0.8 cm×1.2 cm - 1.9 cm×4.3 cm) without fracture or tendon injury. The surgical procedure involved a harvest of flap (1.0 cm×1.4 cm - 1.9 cm×4.5 cm in size) with 1-2 proximal veins and had the redundant veins ligated. Micro-anastomosis was performed between the veins carried by flap and the veins at recipient site. Donor sites were closed primarily or reconstructed with full-thickness skin grafting. Postoperative follow-ups were conducted through outpatient clinic and WeChat, including the evaluations of flap viability using the late-term hand flap evaluation criteria, the flap cold tolerance with the Cold Intolerance Symptom Severity (CISS) questionnaire and the digital motion with the Total Active Movement (TAM) system of the Evaluation Trial Standards of Replantation Functional of Hand Surgery of Chinese Medical Association.Results:All 76 flaps achieved complete survival without complication such as an arterial and venous compromise or an infection, except 1 flap that developed a local blister but it healed after dressing changes and removal of sutures. Over the 2 to 32 (mean 6) months of postoperative follow-up, outcomes of surgery were assessed. Sixty-seven flaps were rated as excellent and 9 as good based on the overall condition of the flap in this group. Cold tolerance was excellent for 65 flaps, good for 10 flaps and fair for 1 flap according CISS. Digital function evaluated by the TAM system showed 63 flaps of excellent, 10 of good and 3 of fair. All skin grafts at the donor sites survived well and in good appearance, without obvious depigmentation or pigmentation.Conclusion:Application of a revered fascial pedicled island flap with venous supercharging in reconstruction of finger pulp defect significantly enhances venous outflow, thereby it reduces postoperative complications such as venous occlusion, flap congestion and blistering.