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 pharmacokinetics/pharmacodynamics(PK/PD)parameters and influencing factors in patients with augmented renal clearance(ARC)to provide the basis for the rational use of meropenem.Methods Using the method of retrospective study,the patients with increased renal clearance who used meropenem monitored the concentration from January 2018 to December 2021.The PK/PD parameters of meropenem were analyzed,and multiple linear retrospective analyses discussed the influencing factors of meropenem valley concentration.Results A total of 58 patients were included in the study,and the trough concentration was 1.35[0.23,1.86]μg·mL-1,taking 100%fT＞MIC as PK/PD target value,the compliance rate was 20.69%.The compliance rate of daily dose＜3 g·d-1 was 8.70%,and≥3 g·d-1 was 31.43%,the difference was statistically significant.With MIC of 0.5,1,2,4,and 8 μg·mL-1,PK/PD compliance rates were 62.07%,48.28%,20.69%,8.62%and 0.Respectively.Multiple linear retrospective analyses showed that dose was an independent factor affecting meropenem valley concentration.Conclusion The PK/PD compliance rate of meropenem in patients with augmented renal clearance is low,even if MIC≤0.5 μg·mL-1,the routine dose is difficult to achieve the ideal PK/PD,so the clinical should recognize ARC and perform TDM as soon as possible,and use TDM to guide the medication regimen of meropenem for ARC patients.

Objective:To evaluate the monitoring value of amplitude-integrated electroencephalography (aEEG) in brain injury among neonates with severe hyperbilirubinemia.Methods:This study retrospectively recruited 223 full-term infants with severe hyperbilirubinemia who underwent aEEG in the Department of Neonatology of Guangzhou Women and Children Medical Center from October 2018 to June 2020. Differences in serum bilirubin level and the incidence of acute bilirubin encephalopathy (ABE) between the normal group ( n=180) and abnormal aEEG group ( n=43) were compared. The monitoring value of aEEG in ABE, and its association with brain stem auditory evoked potential (BAEP) and MRI were studied. Two-independent sample t-test, Mann-Whitney U test and Chi-square test were used for comparing the differences between groups. Goodman-Kruskal Gamma was used for correlation analysis. Results:The total serum bilirubin level [(536.2±154.6) vs (422.1±103.0) μmol/L, t=-5.109, P<0.001] and the incidence of ABE [62.8% (27/43) vs 9.4% (17/180), χ2=62.366, P<0.001] in the abnormal aEEG group were significantly higher than those in the normal aEEG group. The sensitivity and specificity of aEEG in the diagnosis of ABE were 61.3% and 91.1%, respectively. With the progression of ABE from warning period to spasmodic stage, more severe voltage suppression (Gamma=0.847, P=0.003), more disordered sleep-wake cycles (Gamma=0.941, P<0.001) and a more frequent epileptic discharge (Gamma=0.976, P<0.001) were observed. Out of the 223 cases, 148 underwent BAEP. The abnormal rate of aEEG in abnormal BAEP group was significantly higher than that in normal BAEP group [32.7% (33/101) vs 6.4% (3/47), χ2=12.040, P=0.001]. The incidence of abnormal voltage in severe abnormal BAEP group was significantly higher than that in mild abnormal BAEP group [20.6% (7/34) vs 2.6% (1/38), χ2=5.858, P=0.016]. The incidence of epileptic discharge in severe abnormal BAEP group was significantly higher than that in mild abnormal BAEP group [32.4% (11/34) vs 2.6% (1/38), χ2=11.413, P=0.001] and moderate abnormal BAEP group [32.4% (11/34) vs 3.5% (1/29), χ2=8.480, P=0.004]. Among the 223 cases, 108 received MRI examination. The incidence of epileptic discharge in the cases with bilirubin brain injury image was significantly higher than those with normal MRI images [28.6% (10/35) vs 2.6% (1/39), χ2=9.864, P=0.002] and those with other abnormal images [28.6% (10/35) vs 2.9% (1/34), χ2=8.451, P=0.004]. Conclusions:aEEG monitoring is helpful in the diagnosis of ABE and can reflect disease severity. Severe hyperbilirubinemia-induced brain injury in neonates mainly manifests as increased and more frequent epileptic discharge on aEEG. There is a correlation between aEEG monitoring with BAEP and MRI findings.

Objective To investigate the clinical effect on incomplete spinal injury by ganglioside intravenous injection combined with intrathecal injection.Methods From January 2011 to January 2015, seventy-nine cases with irreducible articular process interlocking of cervical spine fracture with dislocation of cervical spinal cord injury,underwent one stage anterior and posterior surgical treatment,postoperative routine use of antibiotics to prevent infection,and the hormone,dehydration to promote bone cell growth and neurotrophic drugs treatment.The patients were randomly divided into the intravenous injection group(42 cases),given intravenous injection of monalsialic acid four hexose ganglioside sodium(GM-1)40 mg/d,mecobalamin tablets 0.5 mg/time,3 times/d,30 d oral;the combined intrathecal injection group(37 cases)was given GM-1 40 mg/d,intravenous injection at 15 d after intrathecal injection,1 time a week 40 mg,with a total of 4 weeks.The degree of spinal cord injury was evaluated according to Frankel classification; cervical function was evaluated according to JOA score; bone graft fusion,stability of cervical spine and degree of spinal cord injury were evaluated by imaging.Results The operation time in the intravenous injection group and the combined intrathecal injection group were(4.15 ± 0.65)h and(4.10 ± 0.85)h,and the intraoperative blood loss was(850.50±35.10)ml and(858.60±25.20)ml,respectively,and there were no significant differences between the two groups(t=1.375,1.452,P>0.05).The total dose of GM-1 in the combined intrathecal injection group was(785.20 ± 3.28)mg,significantly higher than that in the intravenous injection group((610.55 ± 5.28) mg),the difference was statistically significant(t=12.542,P<0.05);79 patients were followed up for 12-24 months,with an average of(15.2 ± 1.3)months.The improvement rate of nerve function of the combined intrathecal injection group was(64.35±4.33)%,significantly higher than that in the intravenous injection group (55.50±5.44)%,the difference was statistically significant(t=8.813,P<0.05);the postoperative JOA scores of the intravenous injection group((13.55 ± 1.75)points)and combined intrathecal injection group((12.85 ±1.97)points)were significantly higher than those before the surgery((7.25± 0.83)points,(7.19± 0.93) points),the differences were statistically significant(P<0.05).There was no significant difference in the JOA scores between the two groups before and after the operation(P>0.05).At the last follow-up,X-ray showed bone fusion at the bone graft site,and the internal fixation was good and firm.MR showed that the degeneration signal area of the cervical spinal cord decreased in varying degrees,and edema and inflammatory reaction disappeared.Conclusion Postoperative treatment of ganglioside intravenous injection combined with intrathecal injection is safe and feasible in the treatment of incomplete cervical spinal cord injury caused by cervical fracture dislocation with irreducible articular process interlocking.

Objective To investigate the clinical efficacy of Cerus and cucumis polypeptide injection in the prevention of heterotopic ossification for the drug treatment of traumatic knee joint fracture after operation.Methods To retrospect the analysis about 150 cases with fracture reduction and internal fixation of traumatic around the knee joint fracture from January 2010 to January 2014 in Daliang Hospital of Shunde District of Foshan,including 89 cases of reduction and internal fixation were performed in group A,and with safflower injection infusion therapy,61 cases with allergic constitution were not given by Cerus and cucumis polypeptide injection in group B.According to the activity degree and HSS scoring system,the function of knee joint was evaluated before and after operation.According to the condition of arounding knee joint bone fracture healing and heterotopic ossification in X-ray and CT examination and to compare the correlation of probability between heterotopic ossification and Cerus and cucumis polypeptide injection in traumatic around knee joint fracture.Results All were followed up with 12.0-24.0 months,with average(13.6±2.2)months.Activity of knee joint between group A and B were respectively(47.2±7.3)°,(46.4±6.8)°before treatment,and HSS score of group A and B were respectively(50.8±10.0)points,(51.5±9.6)points,so there were no statistically significant difference(P＞0.05).Activity of knee joint between group A and B were respectively(115.1±6.5)°,(112.1±7.8)°at the time of the last follow-up,and HSS score of group A and B were respectively(86.2±5.0)points,(85.5±7.0)points,so there were no statistically significant difference(P＞0.05).There were statistically significant difference in activity of knee joint and HSS scores in group A or in group B at the time of the last follow-up(t=13.322,12.898,10.052,10.435,P＜0.05).The incidence of heterotopic ossification was 8.99％(8/89)in group A,the incidence of heterotopic ossification was 1.64％(1/61)in group B,there were statistically significant difference between A and B(x2=10.873,P＜0.05).Conclusion During the drug treatment,there is a correlation between heterotopic ossification and Cerus and cucumis polypeptide injection used in traumatic around knee joint fracture after operation.

Objective To investigate the current situation of iodine deficiency disorders and the effect of control measures in Changzhou City, Jiangsu Province, and to provide a basis for making up targeted control measures for iodine deficiency disorders. Methods In 2012, proportional probability sampling method(PPS) was used to select 30 primary schools in seven counties of Changzhou City;50 students aged 8-10 in each school were randomly selected to examine thyroid, and their urine and household salt samples were collected to detect iodine. Thirty pregnant and 15 lactation women were selected to detect their urine iodine in the town where the school was located in. Two drinking water samples were collected to detect iodine in the village where the school was located in. The questionnaire survey of health education was carried out among the children and the housewives. Results A total of 1 500 children were surveyed, and the rate of goiter was 0.07%(1/1 500); the median of urinary iodine was 224.81 μg/L. Five hundred and seventy-two pregnant women and 328 lactation women were surveyed, and the median of urinary iodine was 148.93 μg/L and 147.48 μg/L, respectively. Fifteen hundred salt samples were detected, and the coverage rate of iodized salt was 99.47%(1 492/1 500); the edible rate of qualified iodized salt was 97.67%(1 465/1 500); and the median of salt iodine was 25.46 mg/kg. Sixty water samples were collected, and the median of water iodine was 3.63 μg/L. The health education awareness rates were 77.8%(2 100/2 700) and 88.0%(396/450) of students and housewives, respectively. Conclusion The control effect of iodine deficiency disorders is significant in Changzhou City, and monitoring of iodine nutrition level of special populations should be strengthened.

OBJECTIVETo identify the proteins involved in osteogenic differentiation of beagle dog bone marrow mesenchymal stem cells (BMSCs) and explore its possible regulation mechanism of osteogenic differentiation of BMSCs.

METHODSCultured beagle dog BMSCs were induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) for 7 days. The differentially expressed proteins between cells with osteogenic differentiation and control cells were identified by proteomics analysis based on two-dimensional gel electrophoresis. Q-PCR and Western blotting were used to verify the interested protein of LASP1, ferritin light chain and heavy chain.

RESULTSOsteogenic differentiation was induced successfully in the BMSCs. Twenty differentially expressed proteins were identified by proteomic analysis, including 9 down-regulated and 11 up-regulated ones. Q-PCR and Western blotting demonstrated a significant reduction of LASP1 expression and significant up-regulation of ferritin in the BMSCs after a 7-day induction with rhBMP-2.

CONCLUSIONLASP1, which plays an important role in the regulation of the activity of the cytoskeleton, and ferritin, an important molecule in cellular iron homeostasis, can be critical in the osteogenic differentiation of beagle dog BMSCs induced by rhBMP-2.

Adaptor Proteins, Signal Transducing ; metabolism ; Animals ; Bone Marrow Cells ; cytology ; drug effects ; Bone Morphogenetic Protein 2 ; pharmacology ; Cell Differentiation ; drug effects ; Cells, Cultured ; Cytoskeletal Proteins ; metabolism ; Dogs ; Down-Regulation ; Ferritins ; metabolism ; LIM Domain Proteins ; metabolism ; Mesenchymal Stromal Cells ; cytology ; drug effects ; Osteogenesis ; drug effects ; Proteomics ; Recombinant Proteins ; pharmacology ; Transforming Growth Factor beta ; pharmacology ; Up-Regulation

Objective To study the effect of Alemtuzumab on acute rejection (AR) and graft survival after kidney transplantation.Method Published domestic and foreign literatures regarding the effects of Alemtuzumab used on acute rejection and graft survival were reviewed,and Meta analysis was employed to analyze the Results.Odds ratio (OR) and its 95％ confidence interval (95％ CI) were used as the parameters to evaluate the therapeutic effects.The statistical analyses were performed with RevMan 5.1 software.Result A total of 9 pertinent research articles were reviewed.Meta-analysis of pooled results indicated that Alemtuzumab prevented the recipients of kidney transplantation from acute rejection effectively with half year prevention of OR 0.37 and 95％ CI 0.24-0.58 (P＜0.01),one year prevention of OR 0.43 and 95 ％ CI 0.29-0.64 (P＜0.01),and two year prevention of OR 0.69 and 95％ CI 0.47-1.02 (P ＜ 0.01),respectively.It was revealed that Alemtuzumab could reduce the incidence of acute rejection by 55％ in half year,51％ in one year and 28％ in two years,respectively.No statistically significant difference in graft survival was found between Alemtuzumab group and control group (OR =1.18,95％ CI 0.76-1.85,P =0.46).No statistically significant difference in patients' survival was found between Alemtuzumab group and control group (OR =0.94,95 ％ CI 0.52-1.72,P =0.85).Conclusion Alemtuzumab may effectively prevent the recipients of kidney transplantation from acute rejection,but not obviously influence the graft and patient survival.

Objective To investigate effect of Murphy's law on the nursing safety management of the hemodialysis patients. Methods 4598 hemodialysis cases in a blood purification center of a first class grade A hospital from April to July in 2011 was assigned as pre-implementation group.Then Murphy's law was used in the nursing practice.In the following,another 5683 hemodialysis cases from November in 2011 to January in 2012 were assigned as post-implementation group.The incidence of nursing risks and hemodialysis equipment failures were compared between the two groups.Result The incidences of nursing risks and hemodialysis equipment failures in the post-implementation group were significantly lower than those of the pre-implementation group(P<0.05).Conclusions Murphy’s law is effective for the declines of nursing manipulative defects and hemodialysis equipment failures.Besides,the law can be good for the strengthened awareness of safety and enhanced consciousness of all staff participating in the safety management so as to ensure the safety and quality of hemodialysis.

Objective To explore the optimized method of venous anastomosis for right donor kidney transplantation in rats.Methods Sprague Dawley (SD) rats were used as donors and recipients for homologous rat kidney transplantation.Both bilateral kidneys were harvested from the donor rats (n =45).Ninety rats were used as recipients and divided into 4 groups according to randomly digital table:In groups AC (n =15 each),the right donor kidneys were transplanted into the left nephridial pit of recipients,and endto-side,venous bypass and modified end-toend (donor's proximal end of vena cava was anastomosed to recipients renal Vein followed by ligation of its distal end) venous anastomosis was done,respectively; In the control group (n =45),the left donor kidneys were transplanted into the same side of the recipients,and the conventional end-to-end venous anastomosis was used.Then the intra-operative findings,successful operation rate and postoperative complications were compared between two groups.Results The venous anastomosis time in group B was longer than in groups A,C and control group (P＜0.05),which significantly increased warm ischemia time of donor kidneys and operative time of recipients (P＜0.05).The venous anastomosis time,warm ischemia time of donor kidneys and operative time of recipients showed no significant difference between groups A or C and control group (P＞0.05).The successful operation rate in group C (93.3％)was similar to that in control group (86.7％) (P＞0.05),but higher than in group A (53.3％) and group B (53.3％) (P＜0.05).There was no significant difference in postoperative complications between group A and group C.Conclusion For right donor kidney transplantation,the method of harvesting the right donor kidney with a part of vena cava,and then anastomosing the proximal end to recipients renal vein and ligating the distal end,is highly feasible,efficient and economic.