Extracellular single-unit discharge recording technique was used to examine the effects of Ginkgolide B (BN52021) on the discharges of neurons in CAI area of hippocampal slices and to elucidate the mechanisms involved.The results showed that:(1) In response to the application of ginkgolide B (0.1,1,10 βμmol/L; n =43) into the perfusate for 2 rain,the spontaneous discharge rates (SDR) of 42/43 (97.67%) neurons were significantly decreased in a dose-dependent manner; (2) Pretreatment with L-glutamate (L-Glu,0.2mmol/L) led to a marked increase in the SDR of all 10 (100%) neurons in an epileptiform pattern.The increased discharges were suppressed significantly after ginkgolide B (1 μmol/L) was applied into the perfusate for 2 rain; (3) In 8 neurons,perfusion of the selective L-type calcium channel agonist,Bay K 8644 (0.1 μmol/L),induced a significant increase in the discharge rate of 8/8 (100%) neurons.Ginkgolide B (1 μmoL/L) applied into the perfusate inhibited the discharges of 7/8 (87.5%) slices; (4) In 8 neurons,the broad potassium channels blocker,tetraethylammonium (TEA,1 mmol/L) completely blocked the inhibitory effect of ginkgolide B (1 μmol/L).These results suggest that ginkgolide B can inhibit the electrical activity of CAI neurons.The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and may be concerned with delayed rectifier potassium channel (KDR),which indicated that ginkgolide B play a protective role on the central neurons.

Objective To study the incidence, risk factors and prognosis of central nervous system (CNS) complications after hematopoietic stem cell transplantation ( HSCT) in order to prevent or reduce its occurrence, provide better diagnosis and treatment and improve the survival of the patients.Methods A total of 640 patients who consecutively underwent HSCT in our hospital between May 2001 and December 2007 were included.The clinical outcomes of the patients who developed CNS complications were analyzed.Results The patients received stem cells from haploidentical family members ( Haplo, n = 289 ) , identical siblings (IS, n = 237) , unrelated donors ( URD, n = 83) , unrelated cord blood (n = 14) , syngeneic siblings (n = 9 ) or autologous peripheral blood ( n = 8 ).Fifty-seven of 640 patients (8.9% ) developed CNS complications.The incidences were 12.0%, 13.5% and 3.4% in URD-HSCT, Haplo-HSCT and IS-HSCT respectively ( P <0.001).The incidences of CNS complications were 19.4% and 8.3% in cases who received or did not receive conditioning with TBI ( P = 0.047 ).There was no significant difference in the incidences of CNS complications between children (15.3% ) and adults(8.3% ) (P = 0.072).Similar incidences of CNS complications were seen in patients with hematological malignancies (8.9%) and non-malignant hematological disorders (7.7%)(P = 1.000).Five of the 57 patients developed two kinds of CNS complications.The patterns of CNS complications included relapse (17 cases) , infections (15 cases) , cyclosporine or FK506 encephalopathy (9 cases) , cerebral hemorrhage ( 8 cases) , cerebral infarction (2 cases), Wernicke's encephalopathy (1 case), skull fracture (1 case), drug-related meningitis (1 case), hepatic encephalopathy (3 cases), post-transplant lymphoproliferative disorder (1 case) and undetermined causes (4 cases).The overall mortality in the patients who developed CNS complications was 57.9% and 66.7% of them died of CNS complications.Conclusions CNS complications are not uncommon after HSCT and they have high mortality and poor prognosis.Our data suggest that haplo-HSCT,URD-HSCT and conditioning with TBI, but not the age and types of hematological diseases are the risk factors for development of CNS complications.Relapse and infections are the most common CNS complications in HSCT recipients.Early diagnosis and appropriate management are crucial to the improvement of clinical outcomes in these patients.

Objective To investigate the awareness,willingness,motivation,and influencing factors of outpatients for participating drug clinical trials,and provide references for decision-making of drug clinical trials.Methods An amnonymous survey was conducted in the departments of internal medicine,surgery,gynecology,and obstetrics of a randomly selected tertiary referral center,and the results were statistically analyzed.Results A total of 1 067 available questionnaires were received.The total awareness rate of clinical trials was 31.02％,which was closely correlated with age and the degree of education.40.86％ of respondents were willing to participate in drug clinical trials.And 55.28％ of them chose yes because of the willingness to contribute to the development of medical science.People having cognition on clinical trials had more willingness to participate in drug(OR:1.361,95 ％ CI:1.042-1.777).59.14％ of the respondents refused to participate in drug clinical trials,68.62％ of whom refusing to participate mainly worried about the safety of drugs.57.37％ of the respondents comfirmed that they might change their idea if experts were involved.41.33％ were willing to accept training about clinical trials.Conclusion Investigators'overall cognition on clinical trials is closely correlated with the willingness to participate in drug clinical trials.There should propagandize drug clinical trials to make sure the improvement of drug clinical trial progress.

ObjectiveTo investigate the efficacy of haploidentical blood and marrow transplantation (haplo-BMT) in the treatment of advanced chronic myeloid leukemia (CML).MethodsFrom November 2002 to October 2007,35 patients with advanced CML received haplo-BMT.Eleven patients achieved the second chronic phase (CP2) after treatment with imatinib or chemotherapy or both before pre-conditioning,but there were 13 cases in accelerated phase (AP) and 11 patients in blast phase (BP) at the time of transplantation.By the last follow-up date October 31,2011,the median follow-up time among living patients was 67 months (range,49 to 100 months).ResultsThe cases of HLA-antigen mismatched between donors and recipients as 1,2,and 3 antigens were 1,12,and 22 respectively.The number of mean mononuclear cells and CD34+ cells was (7.19+ 1.37) × 108/kg and (2.54± 1.50) × 106/kg,respectively.All but one patient achieved durable hematopoietic reconstitution. Hyperacute graft-versus-host disease (GVHD) occurred in 28.6％ (10/35) patients.The cumulative incidence of grade Ⅱ to Ⅳ acute GVHD was 48％.Among 27 patients who survived longer than 100 days after transplant,16 (60 ％) had chronic GVHD.Fiveyear overall survival (OS) rate was 46.2％ and 45.5％ in CML-AP and BP (P =0.97),respectively.Five-year probability of OS rate was 81.8％,30.8％ and 27.3％ in patients with CML-CP2,CML-AP and BP at transplant,respectively.The OS of CML-CP2 was significantly higher than CML-AP and BP at transplant (P＜0.01 ).ConclusionHaplo-BMT is a feasible therapeutic mean for patients with advanced CML who have no matched donors available.It is better to perform haplo-BMT at CML-CP2 other than CML-AP or BP.

The task of segmenting histiocyte is a crucial step in the analysis of histiocytic images which is an important application of computer vision to histopathology. The algorithm presented in this article was composed of two steps: (1) the morph-based preprocessing; (2) the ameliorated watershed method. In the first step, the difference between histiocytes was magnified in order to increase the visibility from the view of the computer vision, and then the ameliorated terrace-flooding-simulated watershed method was used to achieve the segmentation of histiocytic images in the second step. To test the performance of the algorithm, different samples of visual quality were tested and the result figures proved successful.
Algorithms ; Bone Marrow Cells ; cytology ; Cartilage ; cytology ; Histocytological Preparation Techniques ; methods ; Humans ; Image Processing, Computer-Assisted ; methods ; Numerical Analysis, Computer-Assisted ; Pattern Recognition, Automated ; methods

Objective　To analyze the risk factors of stroke-associated pneumonia (SAP) in patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis.Methods　A total of 798 patients with AIS who received intravenous thrombolysis therapy with alteplase from the Department of Neurology,Yangpu Hospital,Tongji University from January 2016 to December 2020 were retrospectively selected and divided into pneumonia group and non-pneumonia group according to the presence or the absence of SAP.The clinical of the two groups were compared.Multivariate logistic regression analysis was used to analyze the independent risk factors of SAP.Results　Of 798 cases,115 cases occurred SAP.By multivariate logistic regression analysis,age≥70 years(OR=2.846,95%CI 2.311~5.083,P<0.001),diabetes(OR=2.291,95%CI 1.601~3.945,P=0.003),chronic obstructive disease(OR=2.064,95%CI 1.759~3.528,P=0.005),NIHSS score at admission>8(OR=1.814,95%CI 1.502~2.452,P<0.001),unconsciousness(OR=2.325,95%CI 2.005~3.404,P=0.008),dysphagia(OR=2.457,95%CI 2.221~4.017,P<0.001),hemorrhagic transformation(OR=1.828,95%CI 1.653~2.523,P=0.012) were independent risk factors of SAP in AIS patients treated with intravenous thrombolysis.Conclusion　Age≥70 years,diabetes,chronic pulmonary disease,NIHSS score at admission,unconsciousness,dysphagia,hemorrhagic transformation were independent risk factors of SAP in AIS patients treated with thrombolysis.

Objective:To summarize clinical characteristics of and treatment experience with patients with critical illnesses in a dermatological ward.Methods:All patients with serious or life-threatening conditions, who were hospitalized at the dermatological ward of the Second Xiangya Hospital of Central South University from July 9, 2011 to December 31, 2020, were collected, and their clinical data were retrospectively analyzed. Demographic characteristics, disease types and proportions, main complications, causes of serious or life-threatening conditions, important treatment measures and outcomes were summarized, and causes of death were also analyzed and discussed.Results:A total of 1 057 patients with critical illnesses were collected, with a male-to-female ratio of 1∶1.11, and 64.81% of them aged 18 to 65 years. The types of diseases mainly included drug eruptions (332 cases) , connective tissue diseases (226 cases) , bullous skin diseases (104 cases) , psoriasis (57 cases) , erythroderma (45 cases) , infectious skin diseases (67 cases) , etc. Among them, psoriasis (39 cases) and erythroderma (32 cases) mostly occurred in males, and connective tissue diseases (168 cases) mostly occurred in females. Common complications mainly involved infections, important organ damage or dysfunction, hypoalbuminemia, and fluid, electrolyte and acid-base imbalances. A total of 94 patients were diagnosed with life-threatening conditions, which were found to be mainly caused by primary skin diseases, hematologic abnormalities, respiratory failure, nervous system abnormalities, renal failure, sepsis, fluid, electrolyte and acid-base imbalances, etc. During the management of critical illnesses, 43 patients were treated with high-dose glucocorticoid pulse therapy, 264 were treated with gamma-globulin pulse therapy, 355 were transfused with other blood products, and 34 received special therapies such as hemoperfusion/immunoadsorption therapy, plasma exchange, dialysis, artificial liver support therapy; 42 patients were transferred to the intensive care unit (ICU) , 12 were transferred to the department of surgery for operations, and 12 were transferred to the department of obstetrics and gynecology for delivery or induction of labor. After treatment, 989 patients (93.57%) achieved improvement and were discharged. A total of 14 patients (1.32%) died, of whom 7 died of secondary sepsis, 2 died of severe pulmonary infections, 2 died of asphyxia caused by respiratory mucosa shedding-induced airway obstruction, the other 3 died of gastrointestinal hemorrhage, cerebral hemorrhage and neuropsychiatric systemic lupus erythematosus, respectively.Conclusions:Critical cases in the dermatological ward mainly suffered from serious skin diseases such as severe drug eruptions, connective tissue diseases and bullous skin diseases, as well as complications such as severe underlying diseases, severe organ dysfunction, sepsis or severe fluid, electrolyte and acid-base imbalances. In terms of treatment, it is of critical significance to make a clear diagnosis and assess the severity of disease as early as possible, monitor and prevent possible complications, and to consult with specialists in relevant disciplines in time.

Alzheimer’s disease （AD）is a common latent neurodegenerative disease ，which is characterized by cognitive impairment，loss of learning and memory function ，abnormal behavior and dementia. At present ，there is no specific drug to effectively prevent or reverse AD. Gardenia jasminoides is the dried and mature fruit of G. jasminoides J. Ellis ，a gardenia plant in Rubiaceae. Its chemical components mainly include iridoids ，triterpenoids，organic acids and volatile oils ，among which iridoids are the main active components of G. jasminoides . This paper summarizes the researches on the mechanism of iridoids from G. jasminoides against AD at home and abroad in recent years ，in order to provide reference for the development of new drugs against AD.

An effective therapeutic regimen for hepatic fibrosis requires a deep understanding of the pathogenesis mechanism. Hepatic fibrosis is characterized by activated hepatic stellate cells (aHSCs) with an excessive production of extracellular matrix. Although promoted activation of HSCs by M2 macrophages has been demonstrated, the molecular mechanism involved remains ambiguous. Herein, we propose that the vitamin D receptor (VDR) involved in macrophage polarization may regulate the communication between macrophages and HSCs by changing the functions of exosomes. We confirm that activating the VDR can inhibit the effect of M2 macrophages on HSC activation. The exosomes derived from M2 macrophages can promote HSC activation, while stimulating VDR alters the protein profiles and reverses their roles in M2 macrophage exosomes. Smooth muscle cell-associated protein 5 (SMAP-5) was found to be the key effector protein in promoting HSC activation by regulating autophagy flux. Building on these results, we show that a combined treatment of a VDR agonist and a macrophage-targeted exosomal secretion inhibitor achieves an excellent anti-hepatic fibrosis effect. In this study, we aim to elucidate the association between VDR and macrophages in HSC activation. The results contribute to our understanding of the pathogenesis mechanism of hepatic fibrosis, and provide potential therapeutic targets for its treatment.
Humans ; Hepatic Stellate Cells/pathology* ; Receptors, Calcitriol ; Liver Cirrhosis/pathology* ; Macrophages/metabolism*