Astrocytes are a crucial type of glial cells in the central nervous system, not only maintaining brain homeostasis, but also actively participating in the transmission of information within the brain. Astrocytes have a complex structure that includes the soma, various levels of processes, and end-feet. With the advancement of genetically encoded calcium indicators and imaging technologies, researchers have discovered numerous localized and small calcium activities in the fine processes and end-feet. These calcium activities were termed as microdomain calcium activities, which significantly differ from the calcium activities in the soma and can influence the activity of local neurons, synapses, and blood vessels. This article elaborates the detection and analysis, characteristics, sources, and functions of microdomain calcium activities, and discusses the impact of aging and neurodegenerative diseases on these activities, aiming to enhance the understanding of the role of astrocytes in the brain and to provide new insights for the treatment of brain disorders.
Astrocytes/cytology* ; Humans ; Animals ; Calcium/metabolism* ; Calcium Signaling/physiology* ; Brain/physiology* ; Aging/physiology* ; Membrane Microdomains/physiology* ; Neurodegenerative Diseases/physiopathology*

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Sterol-regulatory element binding proteins (SREBPs) are the key transcriptional regulators of lipid metabolism. The activation of SREBP requires translocation of the SREBP precursor from the endoplasmic reticulum to the Golgi, where it is sequentially cleaved by site-1 protease (S1P) and site-2 protease and releases a nuclear form to modulate gene expression. To search for new genes regulating cholesterol metabolism, we perform a genome-wide CRISPR/Cas9 knockout screen and find that partner of site-1 protease (POST1), encoded by C12ORF49, is critically involved in the SREBP signaling. Ablation of POST1 decreases the generation of nuclear SREBP and reduces the expression of SREBP target genes. POST1 binds S1P, which is synthesized as an inactive protease (form A) and becomes fully mature via a two-step autocatalytic process involving forms B'/B and C'/C. POST1 promotes the generation of the functional S1P-C'/C from S1P-B'/B (canonical cleavage) and, notably, from S1P-A directly (non-canonical cleavage) as well. This POST1-mediated S1P activation is also essential for the cleavages of other S1P substrates including ATF6, CREB3 family members and the α/β-subunit precursor of N-acetylglucosamine-1-phosphotransferase. Together, we demonstrate that POST1 is a cofactor controlling S1P maturation and plays important roles in lipid homeostasis, unfolded protein response, lipoprotein metabolism and lysosome biogenesis.

Aim To study the mechanisms of the pro-tective effect of procyanidin B2 ( PCB2 ) on the myocar-dial cell apoptosis induced by lipopolysaccharide ( LPS) . Methods Using the primary culture rat myo-cardial cells, myocardial cell injury model was induced by LPS. PCB2 low, medium and high dose groups, were cultured with 6. 25 , 12. 5 , 25. 0 μmol · L-1 PCB2 respectively in DMEM medium for 24 h continu-ously. Myocardial cell survival rate was determined by MTT colorimetric method. Cardiacmyocyte NOX activi-ty was determined by lucigen chemiluminescence meth-od . Western blot analysis was used to detect myocardi-al NADPH oxidase p47phox expression. TUNEL method was used to detect apoptosis and flow cytometry was used to determine the content of myocardial cells ROS. Results Compared with control group, the cell dam-age induced by LPS group myocardial cell survival rate significantly decreased ( P <0. 01 ) , and myocardial cell NOX activity, p47phox expression, apoptotic cell number and ROS content were significantly increased (P<0. 01). PCB2 low, medium and high dose groups cell survival rates were significantly elevated, myocar-dial cell NOX activity and p47phox expression, apoptotic cell number and the ROS content decreased significant-ly in a dose-dependent manner ( P <0. 01 ) . Conclu-sion PCB2 protects myocardial cell apoptosis induced by LPS via inhibiting the expression of NADPH oxidase activation, p47phox expression and reactive oxygen spe-cies generation.

Aim To explore the protective effects of LPPC ( procyanidins extracted from the litchi pericarp) on cardiomyocyte apoptosis in septic rats and its mech-anisms. Methods The rats were randomly divided in-to 5 groups, and were given orally the drug for two weeks continuously. The control group ( control) and sepsis model group ( LPS ) were given distilled water once a day. LPPC low, medium and high dose groups were given LPPC 50 , 100 , 200 mg · kg-1 · d-1 re-spectively which were prepared freshly every day. After the treatment, sepsis animal models were established. Except for the control group, other groups were injec-ted LPS (lipopolysacchride, 10mg·kg-1) intraperito-neally to induce acute sepsis model. 4hrs later, rat se-rum was collected, isoenzyme ( CK-MB ) , lactate de-hydrogenase ( LDH ) and activity of aspertate amin-otransferase ( AST/GOT) were detected. Then rat car-diac tissue was obtained and cardiac tissue malondial-dehyde ( MDA ) , total antioxidant capacity ( T-AOC ) and reduced glutathione ( GSH ) content were deter-mined. TUNEL staining was performed to analyze the apoptosis of myocardial cells. Cleaved caspase-3 and TNF alpha protein expressions were analyzed by West-ern blot. Results Compared with the control group ( control) , serum of sepsis model group rats CK-MB, LDH, AST/GOT and cardiac tissue MDA content were significantly increased (P<0. 01). At the same time, the activity of cardiac tissue T-AOC and GSH de-creased obviously ( P<0. 01 ) . The apoptotic myocar-dial cells increased significantly ( P<0. 01 ) , and the expression level of cleaved caspase-3 and TNF alpha decreased obviously ( P <0. 01 ) . LPPC pretreatment significantly decreased the serum CK-MB, LDH, AST/GOT and tissue MDA content, increased tissue T AOC and GSH activity, attenuated apoptosis of rat myocardi-al cells significantly, and decreased expression level of cleaved caspase-3 and TNF alpha. Conclusion LPPC pretreatment can significantly attenuate rat myocardial cell apoptosis induced by sepsis, and the underlying mechanisms may be related to its anti-oxidative effects.

Objective To evaluate the short-term efficacy and toxicity of the combination of gimeracil and oteracil porassium ( S-1 ) and cispla-tin in the treatment of advanced gastric carcinoma.Methods Fifty-six patients with advanced gastric carcinoma were randomly divided into two groups with 28 cases in each group.Experimental group was treated with S-1 (60 mg bid d1 -d21) combined with cisplatin (60 mg· m-2 iv d1-d3) with 4 weeks as a cycle.While control group was treated with oxaliplatin (130 mg· m-2 iv d1), tegafur (600 mg· m-2 iv d1-d5), calcium folinate ( 120 mg · m-2 iv d1 -d5 ) with 3 weeks as a cycle.Short-term efficacy and adverse reactions were evaluated after three cy-cles.Results The tumor response rate of experimental group and control group was 75.0%and 42.9%(P<0.05).Besides, compared with the con-trol group , the occurrence of gradeⅢ-Ⅳadverse reactions in experimental group were apparently lower.Conclusion The regimen of S -1 combined with cisplatin has shown a better efficacy in the treatment of patients with ad-vanced gastric carcinoma , and the toxicity is relatively mild and tolerable .

INTRODUCTIONThe role of soluble OX40 ligand (sOX40L) in adult bronchial asthma is unclear. This study aims to determine the serum concentrations of sOX40L in adult patients with bronchial asthma, and discussed its relationship with pulmonary function.

MATERIALS AND METHODSWe measured the pulmonary function using the spirometer and detected the serum concentrations of sOX40L by enzyme linked immunosorbent assay (ELISA) in 19 healthy persons in the control group, 58 acute asthmatic adult patients who were grouped according to their disease severity: 18 mild grade, 24 moderate grade, 16 severe grade, and 24 persons in a stable asthmatic group.

RESULTSThe serum concentrations of sOX40L in asthmatic adult patients (6.80 ± 4.95 ng/L) were distinctly higher than those in the control group (3.98 ± 2.83 ng/L, P <0.05), and they were negatively correlated with pulmonary function indexes (FEV1%, FVC%, FEV1/FVC) (r = -0.754, P <0.01, r = -0.557, P <0.01, r = -0.457, P <0.01, respectively). Moreover, the serum concentrations of sOX40L showed obvious differences among control, mild, moderate, and severe groups (3.98 ± 2.83, 4.87 ± 1.89, 6.97 ± 5.91, 8.71 ± 5.18 ng/L, respectively; P <0.01). The concentrations of sOX40L decreased to the same extent as the control group after therapeutic treatments were provided to the asthmatic adult patients.

CONCLUSIONThe concentrations of sOX40L were found to be high in adult asthmatic patients and were associated with the severity of the disease. Therefore, sOX40L could be a potential inflammatory mediator in the pathogenesis of asthma.

Adult ; Analysis of Variance ; Asthma ; blood ; etiology ; physiopathology ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Forced Expiratory Volume ; Humans ; Inflammation Mediators ; blood ; Lung ; physiopathology ; Male ; Middle Aged ; OX40 Ligand ; blood ; Severity of Illness Index ; Spirometry

ObjectiveTo investigate the prevalence and distribution characteristics of dental fluorosis of children aged 8 - 12 in Wushan and Fengjie counties of Chongqing and to provide a scientific basis for prevention and control of the disease.MethodsTwenty townships(towns) in Fengjie county and 18 in Wushan county were selected as survey points by random cluster sampling in 2010.Dental fluorosis of all the children aged 8 - 12 was examined with Dean index.The detection rate of children's dental fluorosis,defect rate and dental fluorosis index were compared between the two counties.Results Totally 38 209 children aged 8 - 12 were investigated.The total detection rate of dental fluorosis was 43.09％( 16 466/38 209) in the two counties.The detection rates of dental fluorosis in Wushan and Fengjie were 48.98％ (9397/19 186)and 37.16％(7069/19 023),respectively,and the difference was statistically significant(x2 =544.03,P ＜ 0.01 ).Total detection rates of dental fluorosis of the five age groups(8,9,10,11,and 12-year-old age groups) were 32.52％(2157/6632),40.07％(2672/6668),43.67％(3420/7831 ),46.01％ (3861/8391) and 50.14％ (4356/8687),respectively,and the difference was statistically significant (x2 =510.50,P ＜ 0.01),Dental fluorosis indexes in Wushan and Fengjie were 0.713 and 0.485,respectively.Defect rates of dental fluorosis in Wushan and Fengjie were 4.05％ (777/19 186) and 1.57％(298/19 023),respectively.Conclusions The total detection rate of dental fluorosis of the two counties is still high,which gradually increases with age.Wushan is still an endemic area of dental fluorosis,and Fengjie is at the edge of the

OBJECTIVETo summarize the experience and lessons from 100 cases retropubic radical prostatectomy performed in the past 10 years.

METHODSFrom July 1999 to July 2009, we performed 100 cases of retropubic radical prostatectomy, of which 84 were followed up for 3 - 120 months. We analyzed their preoperative age, PSA level, amount of intraoperative blood transfusion, operation time, urinary continence, penile erectile function, stricture of the anastomotic stoma and Qmax.

RESULTSThe mean age, PSA level, amount of intraoperative blood transfusion, operation time were 66.8 yr, 20.1 ng/ml, 585.7 ml and 198.9 min; the recovery rates of bladder control at 3, 6 and 12 months postoperatively were 65.5%, 81.7% and 92.4%, respectively. At 12 months after surgery, penile erection was restored in 19 cases (42.2%), anastomotic stoma stricture developed in 5 (5.9%), Qmax averaged 20.5 ml/min, biochemical recurrence was found in 13, and 1 died from prostate cancer.

CONCLUSIONRetropubic radical prostatectomy is a desirable procedure for the treatment of local prostate cancer, in which ligation of the puboprostatic ligament and prostatic venous plexus before cutting off the ligament helps improve urinary continence, protection of the neurovascular bundle and collateral pudendal artery contributes to the recovery of penile erectile function, and proper connection of urethral and bladder mucosa can reduce anastomotic stoma stricture. Postoperative external-beam radiotherapy for those with T3a or local lymph node metastasis could decrease biochemical recurrence.

Aged ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prostatectomy ; methods ; Prostatic Neoplasms ; surgery

This study was purposed to investigate the clinical features and related factors influencing prognosis of patients with severe intestinal graft-versus-host disease (siGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). 710 patients received allo-HSCT in Beijing Dao-Pei hospital from Jan 2007 to Jan 2011 were enrolled in this study. A total of 34 patients with siGVHD out of 710 patients were analyzed retrospectively, and the univariate analysis for related factors influencing prognosis were carried out by using SPSS 19.0 software. The results showed that the incidence of siGVHD was 4.79%, its medium occurrence time was 29 (18 - 210) days after allo-HSCT. 18 out of 34 patients with siGVHD received colonoscopy, among them 6 patients were complicated with viral enteritis. The deep ulcers could be found under colonoscope. Histopathologic examination revealed the viral inclusion bodies or positive viral antigen. Methylprednisolone (MP), cyclosporine A (CsA) or tacrolimus combined CD25 monoclonal antibody and oral budesonide were used for treatment of siGVHD. 29 out of 34 cases achieved complete response (CR) with CR rate of 85.29%, overall survival rate was 58.82% (20/34). 9 out of 29 cases achieving CR died of other complications. The univariate analysis of the related factor indicated the hyperacute GVHD is the adverse factor influencing overall survival of patients with siGVHD. It is concluded that early colonoscopy is an effective way for definitive diagnosis of siGVHD. The combined treatment including MP, CsA or tacrolimus, CD25 monoclonal antibody and oral budesonide shows a significant curative effects. Intensive treatment of complications in late period of GVHD can enhance the overall survival rate.
Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Gastrointestinal Tract ; Graft vs Host Disease ; diagnosis ; etiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Young Adult