Objective To investigate the optimal scan time of MRI using the imaging probe alphamethyl-L-tryptophan(α-MTrp)-superparamagnetic iron oxide nanoparticles (SPIONs) for localizing temporal lobe epilepsy (TLE) foci.Methods α-MTrp-SPIONs were injected into rat models of TLE through the tail vein during the acute and chronic stages (72 h and 8 weeks after status epilepticus,respectively).MRI was performed before and 1,2,4,8,24 h after the injection in all animals,and the T2 values of the epileptogenic regions were measured.One-way repeated measures analysis of variance was used for data analysis.Results Compared with the T2 values before the injection of α-MTrp-SPIONs,the T2 signal of epileptogenic regions after the injection had a negative increased change.The T2 values before and 1,2,4,8,24 h after the injection in acute stage were 112.08±5.85,107.83±6.59,105.08±6.79,95.58±5.14,100.92± 5.81,105.17±6.31 respectively,and those in chronic stage were 112.08±7.53,107.75±7.10,102.75± 5.50,96.17±5.01,97.75±4.37,102.92±4.74.The T2 values after the injection were significantly different from those before the injection (both P＜0.01).The T2 value at 4 h after the injection decreased mostly.Conclusions α-MTrp-SPIONs can precisely localize epileptogenic regions of TLE on MRI.The optimal scan time is 4 h after the injection.

This study was aimed to prepare the polyclonal antibody against the soluble proliferation-inducing ligand (sAPRIL) antigen and to investigate its effects in suppressing sAPRIL mediated lymphocyte proliferation. Mutated recombinant sAPRIL protein, which lacks biological activity but maintains immunogenicity, was used as antigen to immunize humanized SCID mice. Sera were obtained at 6 weeks after immunization. Indirect ELISA and Western blot were used to detect the antibody titer and specificity. The inhibition of polyclonal antibodies on Raji and Jurkat cell proliferation stimulated by sAPRIL was assessed by the MTT assay. The results showed that the mutant of sAPRIL could induce the production of polyclonal antibodies against human sAPRIL. Western blot and indirect ELISA analyses indicated that the anti-serum had higher specificity with a titer of 1:640. Functional analysis revealed that these polyclonal antibodies significantly inhibited the proliferation of Raji and Jurkat cell stimulated by sAPRIL (p < 0.05). It is concluded the polyclonal antibody against human sAPRIL is successfully prepared, which can inhibit the proliferation of Raji and Jurkat cells stimulated by sAPRIL in vitro.
Animals ; Antibodies ; genetics ; immunology ; pharmacology ; Antibody Specificity ; immunology ; Cell Proliferation ; drug effects ; Cloning, Molecular ; Humans ; Immune Sera ; analysis ; immunology ; Jurkat Cells ; Mice ; Tumor Necrosis Factor Ligand Superfamily Member 13 ; genetics ; immunology

Major and profound changes have taken place in China over the past 30 years. Rapid socioeconomic progress has exerted a great impact on lifestyle, ranging from food, clothing, working and living conditions, and means of transportation to leisure activities and entertainment. At the same time, new health problems have emerged, and health services are facing new challenges. Presently, cardiovascular diseases (CVD) are among the top health problems of the Chinese people, and pose a serious challenge to all engaged in the prevention and control of these diseases. An epidemic of CVD in China is emerging as a result of lifestyle changes, urbanization and longevity. Both national policy decision-making and medical practice urgently need an authoritative report which comprehensively reflects the trends in the epidemic of CVD and current preventive measures. Since 2005, guided by the Bureau of Disease Prevention of the Ministry of Health of the People's Republic of China and the National Center for Cardiovascular Diseases of China, nationwide experts in the fields of epidemiology, clinical medicine and health economics in the realms of CVD, cerebrovascular disease, diabetes and chronic kidney disease, completed the Report on Cardiovascular Diseases in China every year. The report aims to provide a timely review of the trend of the epidemic and to assess the progress of prevention and control of CVD. In addition, as the report is authoritative, representative and readable, it will become an information platform in the CVD field and an important reference book for government, academic institutes, medical organizations and clinical physicians. This publication is expected to play a positive role in the prevention and control of CVD in China. We present an abstract from the Report on Cardiovascular Diseases in China (2010), including trends in CVD, morbidity and mortality of major CVDs, up-to-date assessment of risk factors, as well as health resources for CVD, and a profile of medical expenditure, with the aim of providing evidence for decision-making in CVD prevention and control programs in China, and of delivering the most authoritative information on CVD prevention and control for all citizens.
Arrhythmias, Cardiac ; epidemiology ; prevention & control ; China ; epidemiology ; Coronary Disease ; epidemiology ; mortality ; prevention & control ; Diabetes Complications ; epidemiology ; Diet ; Dyslipidemias ; complications ; epidemiology ; Epidemics ; Heart Failure ; epidemiology ; mortality ; prevention & control ; Humans ; Hypertension ; complications ; epidemiology ; Kidney Failure, Chronic ; epidemiology ; mortality ; prevention & control ; Metabolic Syndrome ; Motor Activity ; Nutritional Physiological Phenomena ; Overweight ; complications ; epidemiology ; Peripheral Arterial Disease ; epidemiology ; prevention & control ; Risk Factors ; Smoking ; adverse effects ; Stroke ; epidemiology ; mortality ; prevention & control

OBJECTIVETo observe the basic characteristics of rats with subluxation, which was hypomobility of motion.

METHODSOne hundred and eight male SD rats (weighted, 350 to 450 g) were randomly divided into experimental group (simple fixation and rotatory fixation) and sham operation group. Each group was subdivided into four groups, including 2, 4, 8 and 12 weeks sub-groups. Simple fixation and rotatory fixation group were modeled by implanting external linked fixation system; Sham operation group was dealed with operation intervention. At the end of connection, X-ray films was used to observe posterier body angle (PBA); Spinal stiffness system for stiffness in simple fixation group and rotatory fixation group.

RESULTSRadiographic results showed that variation of PBA n experimental groups tended to decrease; and there was no significant difference between simple fixation group and rotatory fixation group at the end of linking time (P > 0.05). But there was significant difference between the experimental group and sham operation group (P < 0.05). The degree of stiffness showed that the stiffness in experimental group increased with the linking time, but no meaning between groups (P > 0.05).

CONCLUSIONRats with subluxation induced by external linked fixation system can effectively change biomechanical characteristics of spine, reduced the motion with linking time.

Animals ; External Fixators ; Fracture Fixation ; Humans ; Joint Dislocations ; physiopathology ; surgery ; Lumbosacral Region ; injuries ; physiopathology ; surgery ; Male ; Range of Motion, Articular ; Rats ; Rats, Sprague-Dawley

Objective To clarify the effect of histamine H4 receptor antagonist, JNJ 7777120, and histamine H1 receptor antagonist, Loratadine, on allergic rhinitis ( AR) in rats and to study the role of histamine H4 receptor antagonist and histamine H1 receptor antagonist in the pathogenesis of allergic rhinitis and therapeutic value of their antagonist. Methods AR animal model were induced by ovalbumin ( OVA) in the Wistar rats, which treated with histamine H4 receptor antagonist and (or) histamine H1 receptor antagonist. The allergic symptoms (sneezing and nasal rubbing) , serum total IgE and the levels of cytokines in serum or nasal lavage fluid were measured, the diversity between two groups were observed. Statistical analysis was performed using a SPSS 13. 0 software. Results Compared with AR group with no treatment, the inhibition of nasal symptoms ( P < 0. 01), a significant decrease in the levels of IgE, IL-4 in serum and Eotaxin in nasal lavage fluid(P <0. 01), a significant increase in the levels of IFN-μ in serum(P <0. 01 ) after treatment was found. Compared with group treated with Loratadine, inhibition of nasal symptoms (q value were 3.72, 4. 16, P < 0. 01), a significant increase in the levels of IgE and IL-4 in serum (q value were 8. 01, 4. 96, P <0. 05) , a significant decrease in the levels of IFN-γ in serum( q =3. 18, P <0. 05) ingroup treated with JNJ 7777120 also,but no significant differences in the levels of Eotaxin in nasal lavage fluid(P > 0.05). Administration of JNJ 7777120 and Loratadine jointly, neither additive effect nor synergistic action were found ( P > 0. 05). Conclusions Histamine H4 receptor is closely related with allergic rhinitis and is important in the pathogenesis of allergic rhinitis, the same as histamine H1 receptor. Histamine H4 receptor antagonist, JNJ 7777120, could relieve symptoms and inflammatory conditions in allergic rhinitis, the effect was weak compared with Loratadine. Neither additive effect nor synergistic action were found between them.

Objective To evaluate the effect of tranexamic acid on the blood loss and coagulation function after liver resection in patients with hepatocellular carcinoma (HCC).Methods Seventy patients with hepatectomy who underwent liver resection were randomly divided into control group and treatment group,each group 35 cases.Control group was given 0.9％ NaCl injection 10 mg · kg-1.Treatment group was given tranexamic acid 10 mg · kg-1.Two groups were used at half an hour before operation.The surgical bleeding volume and postoperative coagulation function between two groups were compared.Results The operation time,time of hilar occlusion in treatment group were (157.98 ±22.36),(30.14 ±5.64) min,had no significant difference with those in control group,which were (154.98 ± 23.65),(28.79 ± 5.79) min (P ＞ 0.05).The surgical blood transfusion,bleeding volume,infusion of erythrocyte suspension in treatment group were (879.65 ± 59.36) mL,(768.97 ± 45.65) mL,(1.36 ± 0.59) U,had significant differences with those in control group,which were (1054.91 ±61.32) mL,(869.64 ±46.69) mL,(2.01 ±0.65) U (all P ＜0.05).The percentage of activated thromboplastin (APTT),prothrombin time (PT),platelet (PLT) in treatment group at 24 h after operation were (41.56 ±5.46)s,(13.48 ±3.16)s,(167.89 ±35.87) × 109/L,had no significant difference with those in control group,which were (43.19 ± 5.69) s,(14.59 ± 2.49) s,(162.35 ± 41.59) × 109/L (all P ＞0.05).The fibrinogen (FIB) in treatment group and control group were (3.27 ±0.56),(3.01 ±0.59)g · L-1,with significant difference (P ＜ 0.05).There was no adverse drug reactions in two groups during the treatment.Conclusion Giving methotrexate injection to hepatocarcinoma patients before liver resection can reduce the amount of surgical bleeding,and improve the patients' postoperative coagulation function.

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment

OBJECTIVETo evaluate the clinical function and significance of establishing a regional active neonatal transport network (ANTN) in Beijing.

METHODThe authors retrospectively studied intensive care and the role of ANTN system in management of critically ill neonates and compared the outcome of newborn infants transported to our NICU before and after we established standardized NICU and ANTN system (phase 1: July 2004 to June 2006 vs phase 2: July 2006 to May 2008).

RESULTThe number of neonatal transport significantly increased from 587 during phase 1 to 2797 during phase 2. Success rate of transport and the total cure rate in phase 2 were 97.85% and 91.99% respectively, which were significantly higher than those in phase 1 (94.36% and 88.69%, respectively, P < 0.01). The neonatal mortality significantly decreased in phase 2 compared with that in phase 1 (2.29% vs 4.31%, P < 0.01). The capacity of our NICU was enlarged following the development of ANTN. There are 200 beds for level 3 infants in phase 2, but there were only 20 beds in phase 1. Significantly less patients in the phase 2 had hypothermia, acidosis and the blood glucose instability than those in phase 1 (P < 0.01, 0.05, 0.01 and 0.05, respectively). The proportion of preterm infants transported to our NICU were higher in phase 2 compared with that in phase 1, especially infants whose gestational age was below 32 weeks. The proportions of asphyxia and respiratory distress syndrome were lower in phase 2 than that in phase 1, but the total cure rates of these two diseases had no significant changes between the two phases. The most important finding was that the improvement of outcome of premature infants and those with asphyxia and aspiration syndrome was noted following the development of ANTN.

CONCLUSIONEstablishing regional ANTN for a tertiary hospital is very important to elevate the total level in management of critically ill newborn infants. It plays a very important role in reducing mortality and improving total outcomes of newborn infants. There are still some problems remained to solve after four years practice in order to optimize the ANTN to meet needs of the development of neonatology.

Humans ; Infant Mortality ; Infant, Newborn ; Infant, Premature ; Intensive Care Units, Neonatal ; standards ; Transportation of Patients ; standards

Objective:To compare the prognostic values of different classification by using transpulmonary pressure gradient (TPG), diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) in patients with pulmonary hypertension due to left heart disease (PH-LHD), and investigated hemodynamic and clinical factors associated with mortality in patients with PH-LHD.Methods:This was a single-center prospective cohort study. In-hospital patients diagnosed with PH-LHD via right heart catheterization at the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, from September 2013 to December 2019 were enrolled. Patients were divided according to TPG (cutoff value 12 mmHg; 1 mmHg=0.133 kPa), DPG (cutoff value 7 mmHg), PVR (cutoff value 3 Wood Units), and the combination of TPG and PVR. Baseline characteristic was recorded. All patients were followed up until the occurrence of endpoint event, defined as all-cause death that occurred during the follow-up period, or until April 18, 2022. Receiver operating characteristic curves were used to compare the predictive value of 3 classification methods for all-cause death in PH-LHD patients. The optimal cutoff values were calculated using Jorden index. Survival analysis was performed using Kaplan-Meier analysis, and log-rank test was used to compare the predictive efficacy of classification methods based on optimal cutoff values or guidance-recommended thresholds for the survival of PH-LHD patients. Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality.Results:A total of 243 patients were enrolled, aged (54.9±12.7) years old, including 169 (69.5%) males. During a median follow-up of 57 months, there were 101 (41.6%) deaths occurred. Grouping results were as follows: (1) TPG: TPG≤12 mmHg group 115 patients, TPG>12 mmHg group 128 patients; (2) DPG: DPG<7 mmHg group 193 patients, DPG≥7 mmHg group 50 patients; (3) PVR: PVR≤3 Wood Units group 108 patients, PVR>3 Wood Units group 135 patients; (4) TPG and PVR: TPG≤12 mmHg and PVR≤3 Wood Units group 89 patients, TPG>12 mmHg and PVR>3 Wood Units group 109 patients. PVR ( AUC=0. 698,95% CI:0.631-0.766) had better predictive value for all-cause mortality than TPG ( AUC=0.596, 95% CI: 0.523-0.669) and DPG ( AUC=0.526, 95% CI: 0.452-0.601) (all P<0.05). The optimal cutoff values for TPG, DPG, and PVR were13.9 mmHg, 2.8 mmHg, and 3.8 Wood Units, respectively. Kaplan-Meier analysis based on the optimal cutoff values or guidance-recommended thresholds showed that PVR and TPG were the predictors of survival ( P<0.05), while DPG did not showed significance ( P>0.05). Multivariate Cox regression analysis showed that age, PVR and log 2N-terminal pro-B-type natriuretic peptide were independent risk factors for all-cause mortality in PH-LHD patients (all P<0.05). Conclusion:Classification according to PVR was most valuable in predicting all-cause death in PH-LHD patients, while TPG showed moderate predictive ability and DPG had no predictive value.

OBJECTIVETo systematically review the clinical practice guidelines (CPGs) for ischemic stroke in Chinese medicine (CM) with the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument.

METHODSCM CPGs for ischemic stroke were searched in 5 online databases and hand-searches in CPGrelated handbooks published from January 1990 to December 2012. The CPGs were categorized into evidence based (EB) guideline, consensus based with no explicit consideration of evidence based (CB-EB) guideline and consensus based (CB) guideline according to the development method. Three reviewers independently appraised the CPGs based on AGREE II instrument, and compared the CPGs' recommendations on CM pattern classification and treatment.

RESULTSFive CM CPGs for ischemic stroke were identified and included. Among them, one CPG was EB guideline, two were CB guidelines and two were CB-EB guidelines. The quality score of the EB guideline was higher than those of the CB-EB and CB guidelines. Five CM patterns in the CPGs were recommended in the EB CPG. The comprehensive protocol of integrative Chinese and Western medicine recommended in the EB CPG was mostly recommended for ischemic stroke in the CPGs. The recommendations varied based on the CM patterns.

CONCLUSIONThe quality of EB CPG was higher than those of CB and CB-EB CPGs in CM for ischemic stroke and integrative approaches were included in CPGs as major interventions.

Biomedical Research ; Brain Ischemia ; complications ; therapy ; Health Planning Guidelines ; Humans ; Medicine, Chinese Traditional ; Practice Guidelines as Topic ; Stroke ; complications ; therapy