Acute pancreatitis (AP) is a devastating disease characterized by an inflammatory disorder of the pancreas. P-selectin glycoprotein ligand-1 (PSGL-1) plays a crucial role in the initial steps of the adhesive at process to inflammatory sites, blockade of PSGL-1 might confer potent anti-inflammatory effects. In this study, we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1, RH001-6 and RH001-22, which were screened from immunized rhesus macaques. We found that RH001-6, can effectively block the binding of P-selectin to PSGL-1, and abolish the adhesion of leukocytes to endothelial cells in vitro. In vivo, we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and l-arginine induced AP models. We also evaluated the safety profile after RH001-6 treatment in mice, and verified that RH001-6 did not cause any significant pathological damages in vivo. Taken together, we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity, named RH001-6, which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during AP. Therefore, RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases, such as AP.

Objective:To investigate the efficacy of a SARS-CoV-2 recombinant protein vaccine as a booster dose.Methods:A new immunogen, namely RBD-sc-trimer, was designed by tandem repeating of single receptor binding domain (RBD) of SARS-CoV-2 spike (S) protein to mimic the trimeric form of RBD presented by the virus. The RBD-sc-trimer protein was expressed as a His-tagged fusion protein using a baculovirus expression system and purified by nickel affinity column. The purified protein was identified by Western blot. Its in vitro binding activity to human angiotensin converting enzyme 2 (hACE2) was analyzed by ELISA. The immunogenicity of RBD-sc-trimer as well as RBD proteins of other forms including RBD dimer (RBD-Fc), RBD monomer (RBD) and S protein trimer (S trimer) as a booster dose was evaluated in BALB/c mice. Results:In terms of both binding and neutralizing antibodies against SARS-CoV-2, RBD-sc-trimer showed an immunogenicity that was superior to that of RBD-Fc and RBD and close to the level of S trimer. The antibody response induced by RBD-sc-trimer was characterized as Th1-biased. Moreover, it displayed a stronger cross-neutralization activity against SARS-CoV-2 Beta, Delta and Omicron variants. The titer of neutralizing antibody against Omicron induced by RBD-sc-trimer only decreased by 9.1 folds relative to the prototype strain, while the antibody response induced by RBD-Fc and S trimer decreased by 68.4 and 70.8 folds, respectively.Conclusions:The recombinant protein, RBD-sc-trimer, which was capable of eliciting stronger humoral response in mice as a booster dose and showed the superiority in raising cross-reactive antibodies against SARS-CoV-2 variants over non-trimeric RBD forms, should be considered as an optimal immunogen for the development of more effective SARS-CoV-2 vaccines.

Cost data caliber governance is key to fine cost management. To tackle the troubles in cost data management at multiple campuses of one hospital, the authors built a multi-campus cost data caliber governance mode. By means of enhanced top-level design, the mode carried out data governance by such measures as the establishment of data dictionary mapping library, standardizing department names and caliber, classification of charging items of medical services, precisely matching between fixed assets and charging items, interconnecting the management system of charging library and the procurement library of consumables, as well as precisely matching surgical disease types and charging items. These measures accomplished the consistency and comparability of cost data across campuses, building an automated, streamlined, standardized and integrated data governance mode for reference of hospitals with multiple campuses in need of cost management.

Objective:To investigate the value of artificial intelligence (AI)-assisted quantitative measurement in evaluation of the dynamic changes of CT for COVID-19 pneumonia.Methods:The clinical and chest CT dynamic imaging data of 99 patients with confirmed COVID-19 pneumonia who were hospitalized in Wuhan Central Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 15, 2020 to March 10, 2020 were retrospectively analyzed. According to the definitive diagnosis, the 99 patients were classified into common ( n=36), severe ( n=33) and critical ( n=30) type, the CT imaging findings of each type were analyzed, including CT basic signs, total volume of pneumonia lesions and percentage of pneumonia lesions of the total lung volume (volume ratio). AI software was used to quantitatively evaluate the dynamic changes of chest CT images. The quantitative indicators included CT peak time of lesions, total volume of lesions peak, volume ratio of lesions peak, maximum growth rate of total volume and maximum growth rate of volume ratio. Kruskal-Wallis rank sum test was used to compare the difference of quantitative indexes between the 3 types, and χ 2 test or Fisher exact probability test was used to compare the difference of qualitative indexes between the 3 types. Sequence measurement and scatter plots were used to show the evolution trend of the volume ratio of the three types of COVID-19 pneumonia lesions. The ROC curve was used to analyze the value of the volume ratio of pneumonia lesions and its maximum growth rate in predicting the conversion of common pneumonia to severe or critical pneumonia. Results:There were statistically significant differences in age and gender distribution among patients with common, severe and critical COVID-19 ( P<0.05), the age of severe and critical types were significantly higher than that of common type ( P<0.01). Compared with common [2.5 (1.0, 5.0) d] and critical type[2.5 (1.0, 4.0) d], the time from onset to the first chest CT scan of severe type was prolonged [5.0 (2.5, 8.0) d, P<0.01]. There were statistically significant differences in involvement of multiple lung lobes (20 cases, 29 cases, 25 cases, χ2=10.403, P=0.006) in patients with common, severe and critical COVID-19 at the first scan, the incidence of the involvement of multiple lung lobes in severe and critical types was significantly higher than that of common type ( P=0.002). The volume ratios of patients with common, severe and critical COVID-19 at the first scan were statistically significant [1.0% (0.2%, 4.7%), 9.30% (1.63%, 26.83%), 2.10% (0.64%, 8.61%), Z=14.236, P=0.001], and the volume ratio of severe type was significantly higher than that of common type ( P<0.001), there was no statistically significant difference between common type and critical type ( P=0.062). Follow-up CT showed that the pneumonia lesions showed a dynamic transformation of progress and recovery, and it was seen that the coexistence of multiphase lesions. The trend line in the scatter plot of the three types of COVID-19 pneumonia lesions showed that the lesions in the advanced stage developed from less to more. The lesion peak volume ratios of the common, severe and critical types were 9.75% (4.83%, 13.18%), 29.80% (23.99%, 42.36%) and 61.81% (43.73%, 72.82%), respectively, the difference was statistically significant ( Z=74.147, P<0.001). The maximum growth rates of lesion volume ratio were 1.27% (0.50%, 1.81%)/d, 4.39% (3.16%, 5.54%)/d and 6.02% (4.77%, 9.96%)/d, respectively, the difference was statistically significant ( Z=52.453, P<0.001). The peak times of lesions were 12.0 (9.0, 15.0) d, 13.0 (10.0, 16.0) d and 16.5 (12.0, 25.0)d, respectively, the difference was statistically significant ( Z=9.524, P=0.009). Taking the volume ratio of pneumonia lesion 22.60% and the maximum growth rate of the volume ratio 1.875%/d as the boundary value, the sensitivity of diagnosing common type to severe or critical type was 92.10% and 96.83%, and the specificity was 100% and 80.56%, respectively. The area under the curve was 0.987 and 0.925, respectively. Conclusions:The lesions of COVID-19 pneumonia show a similar parabolic change on CT imaging. The use of AI technology to dynamitcally and accurately measure the CT pneumonia lesion volume ratio is helpful to evaluate the severity of the disease and predict the development trend of the disease. Patients with a rapid growth of volume ratio are more likely to become severe or critical type.

OBJECTIVE：To optimize the p reparation technology of citronellol submicroemulsion. METHODS ：The content of citronellol in Citronellol submicroemulsion was determined by HPLC. Citronellol submicroemulsion by high-speed shearing dispersion-high pressure homogenization method ，with centrifugation stability constant （ke） and particle size were used as evaluation indexes. Its formulation and preparation technology were optimized and validated. Drug-loading amount and encapsulation rate of the preparation were detected. RESULTS ：The linear range of citronellol were 4-64 μg/mL（R 2＝0.999 9）. RSDs of precision ，stability（24 h）and reproducibility tests were all lower than 3％. The recoveries were 97.64％-101.97％（RSD＝ 2.28％，n＝3），97.71％-99.50％（RSD＝1.29％，n＝3），96.87％-101.48％（RSD＝2.86％，n＝3）. The optimal formulation included that total weight of soybean oil and medium chain triglycerides （1 ∶ 1，g/g）was 3.75 g，1.2％ soybean phospholipid was 0.6 g， cholesterol was 0.06 g，citronellol was 1.25 g，0.6 ％ sodium oleate was 0.3 g，15-hydroxystearic acid polyethylene glycol ester was 0.75 g，poloxamer 188 was 0.75 g，water added to 50 mL. After prepared by optimal technology at 4 ℃ which contained shearing speed of 13 000 r/min，lasting for 5 min， primary emulsion was adjusted to pH 7 with dilute hydro- chloric acid ，and homogenized with 600 Bar high pressure for 1434412440@qq.com 5 min. The parameters of Citronellol submicroemulsion accor- ding to optimal formulation and technology contained mean particle size of （91.05±0.26）nm，PDI of （0.20±0.01）， Zeta-potential of （－30.86±0.39）mV，average content of 649511230@qq.com citronellol（100.21±0.01）％，the drug-loading amount was （2.481 7 ± 0.000 7） mg/mL，the encapsulation rate was （99.27 ± 0.03）％ . CONCLUSIONS ：The optimal formulation and technology is stable and feasible.

Background: Two randomized phase III trials (EORTC55971 and CHORUS) showed similar progression-free and overall survival in primary or interval debulking surgery in ovarian cancer, however both studies had limitations with lower rate of complete resection and lack of surgical qualifications for participating centers. There is no consensus on whether neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) could be a preferred approach in the management of advanced epithelial ovarian cancer (EOC) in the clinical practice. Methods The Asian SUNNY study is an open-label, multicenter, randomized controlled, phase III trial to compare the effect of primary debulking surgery (PDS) to NACT-IDS in stages IIIC and IV EOC, fallopian tube cancer (FTC) or primary peritoneal carcinoma (PPC).The hypothesis is that PDS enhances the survivorship when compared with NACT-IDS in advanced ovarian cancer. The primary objective is to clarify the role of PDS and NACT-IDS in the treatment of advanced ovarian cancer. Surgical quality assures include at least 50% of no gross residual (NGR) in PDS group in all centers and participating centers should be national cancer centers or designed ovarian cancer section or those with the experience participating surgical trials of ovarian cancer. Any participating center should be monitored evaluating the proportions of NGR by a training set. The aim of the surgery in both arms is maximal cytoreduction. Tumor burden of the disease is evaluated by diagnostic laparoscopy or positron emission tomography/computed tomography scan. Patients assigned to PDS group will undergo upfront maximal cytoreductive surgery within 3 weeks after biopsy, followed by 6 cycles of standard adjuvant chemotherapy. Patients assigned to NACT group will undergo 3 cycles of NACT-IDS, and subsequently 3 cycles of adjuvant chemotherapy. The maximal time interval between IDS and the initiation of adjuvant chemotherapy is 8 weeks. Major inclusion criteria are pathologic confirmed stage IIIC and IV EOC, FTC or PPC; ECOG performance status of 0 to 2; ASA score of 1 to 2. Major exclusion criteria are non-epithelial tumors as well as borderline tumors; low-grade carcinoma; mucinous ovarian cancer. The sample size is 456 subjects. Primary endpoint is overall survival.

Objective·To explore plasma immune and inflammatory proteins that could serve as potential screening markers for Alzheimer's disease (AD).Methods·Healthy controls (n=19) and AD patients (n=19) were enrolled.Plasma samples were collected and 70 kinds of immune and inflammatory proteins were detected.The immune and inflammatory proteins associated with AD were screened by Mann-Whitney U test and partial correlation analysis.Discriminant analysis was used to develop multi-protein combined algorithm to distinguish plasma samples of AD patients from those of healthy controls.Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy for the multi-protein combined algorithm.Results·Among the 70 proteins analyzed,23 were significantly higher in AD patients (P＜0.05),among which 19 were strongly correlated with AD (P＜0.05).These 19 proteins were analyzed with Wilks' lambda stepwise analysis to develop discriminant algorithm for detecting plasma samples of AD.Finally,the discriminant algorithm established by 11 plasma immune and inflammatory proteins (EGF,GRO,MDC,MCP-1,MCP-2,MCP-4,TARC,SCF,TRAIL,CTACK,GCP-2) was found to have an optimal diagnostic efficacy (AUC=0.994).The optimal cutoff value of the algorithm was-0.609.When the optimal cutoff value was obtained,the sensitivity of the equation could reach 100％ and the specificity could reach 94.7％.Conclusion·The discriminant equation composed of the above 11 plasma immune and inflammatory proteins has the potential to assist AD screening.

ObjectiveTo explore the characteristics and risk factors of suicidal ideation among community subjects in Xiamen city and to provide appropriate suicide intervention strategies.MethodsUsing multi-stage stratified cluster sampling,12071 subjects aged 18 years and older were identified in Xiamen City.Their suicidal ideation was recorded with the investigation list made by Beijing Huilongguan Hospital Beijing Suicide Research and Prevention Center.Psychiatrists determined their diagnosis with Diagnostic and Statistical Manual of Mental Disorder 4th edition (DSM-Ⅳ).ResultsA total of 10757 subjects completed the survey,the completion was 89.1％.The life-time prevalence of suicidal ideation was 2.48％ (95％CI:2.19％ ～ 2.77％ ),the prevalence was higher in female(3.00％ ) than male( 1.88％ ) (RR =1.60,95％CI:1.24 ～2.06).Analysis of risk factors by single logistic regression showed that the suicidal ideation of persons were mostly in female,44 years and older group,in rural,not-being married,no medical insurance,poor mental or physical health in last month,being in hospital due to the mental problems,low quality of life,living alone,having blood relatives or acquaintance with suicidal behavior.While the risk factors by muhivariate logistic regression were ranked as follows:having acquaintance with suicidal behavior (OR =3.66,95％CI:2.44 ～5.50),being in hospital because of mental problems (OR =3.30,95％CI:1.08 ～10.09),poor mental health in last month(OR =3.17,95％CI:2.37 ～4.24),any blood relatives having suicidal behavior (OR =2.91,95％CI:1.61 ～ 5.25 ),low of quality of life (OR =2.21,95％CI:1.50 ～ 3.26 ),not-being married (OR =1.73,95％CI:1.28 ～ 2.32),living alone (OR =1.65,95％CI:1.18 ～ 2.32),being female (OR=1.57,95％CI:1.21 ～ 2.05).The prevalence of mental disorders in suicidal ideation was 46.4％.ConclusionThe prevalence of suicidal ideation is significantly higher in female residents than in male.Having acquaintance with suicidal behavior,being in hospital due to the mental problems as well as poor mental health in last month are the main risk factors of suicidal ideation.

Objective To investigate the toxic effect of the carboxyl-terminal peptide of β-amyloid precursor protein (APPC31) on Neuro2a cells as well as its role in the toxic process in Neuro2a cells induced by Aβ42 in vitro.Methods The plasmid vector and the APPC31 construct were transiently transfected into Neuro2a cells respectively by lipofectamine 2000.The viability of the cells was measured by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay at 48 h after transfection,and their morphocytology was observed by 4', 6-diamidino-2-phenylindole (DAPI) nucleus staining.Afterword different constructs including vector, WTAPP695, APP( D664A), the amino-terminal peptide of β-amyloid precursor protein (APP△C31) and APPC31 were transiently transfected into Neuro2a cells respectively via the same method.At 24 h after transfection Aβ42 was added into the culture medium of Neuro2a cells with the desired concentration for another 24 h for cell studies.The viabihty and morphocytology of the cells were measured by using the MTT assay and DAPI nucleus staining, respectively.Results When incubated in the absence of Aβ42, the viability of cells transfected with vector and APPC31construct were 0.81 ±0.10 and 0.88 ±0.12 respectively, and accordingly there was no significant difference between the these two groups (t = - 0.78, P = 0.48 ); meanwhile no obvious cell nuclear morphological changes of apoptosis or death occurred.However when incubated in the presence of Aβ42, the viability of cells transfected with vector, WTAPP695, APP( D664A), APP△C31 and APPC31 constructs were 0.82 ±0.01, 0.78 ±0.03, 0.55 ±0.04, 0.81 ±0.04, 0.78 ±0.02 and 0.54 ±0.02 respectively.The viability of cells transfected with WTAPP construct and APPC31 construct decreased significantly ( F = 47.53, P ＜0.05) compared with the control group, meanwhile cells displayed condensed nuclear and even nuclear fragmentation.Conclusions In vitro, over-expression of a certain level of APPC31 in Neuro2a cells fails in causing cell death, but this short peptide enhances cytotoxicity induced by Aβ42 in Neuro2a cells.Thus,these results provide the experimental basis for the further explication of the pathogenesis of Alzheimer's disease.

Objective To observe the change of invasion and migration of the pancreatic carcinoma cell line SW1990 transfeeted with EEF1A2 gene.Methods Pancreatic carcinoma cell line SW1990 was transfected with EEF1A2 by recombinant adenovirus vector.The alteration of motility、invasion and adhesion property of SW1990 was evaluated by wound healing assay,transwell With or without Matrigel basement membrane and adhesion assay.Results Wound healing assay revealed that EEF1A2 enhanced cell motility and transwell assay with Matrigel indicated that the average numbers of transwell cells with EEFlA2 was increased from 23.25±5.23 to 65.42±8.24(P＜0.05).The adhesive rate was substantially increased in EEF1A2 transfected SW1990 cells compared with control cells.Conclusions EEF1A2 gene can promote the migration.invasion and adhesion ability of pancreatic cancer cell in vitro.It is indicated that EEF1A2 may involve in the development of human pancreatic cancer by influencing cell biological characteristics.