【Objective】 To explore the risk factors for the production of anti-HLA antibodies in patients with hematological diseases before hematopoietic stemcell transplantation. 【Methods】 The results and clinical data of 1 008 patients with hematological diseases in our hospital who underwent anti-HLA antibody testing were collected by using Luminex technology platform before transplantation from 2016 to 2018 for statistical analysis. 【Results】 The total positive rate of anti-HLA antibodies in 1 008 patients was 24.08%. Multivariate analysis showed that independent risk factors associated with the production of anti-HLA antibodies included age≥30 years old(P=0.046, OR1.467, 95%CI1.007-2.136), time from disease diagnosis to antibody testing≥41 days(P=0.000, OR1.830, 95%CI1.306-2.565), initial platelet count<20×10⁹/L(P=0.020, OR1.543, 95%CI1.072-2.220), prior pregnancy(P=0.000, OR5.187, 95%CI3.689-7.293), transfusions before admission(P=0.001, OR1.762, 95%CI1.257-2.470)and total platelet transfusion volumes after admission≥30 U(P=0.000, OR2.352, 95%CI1.638-3.376). Age ≥30 years old(P=0.023, OR=1.839, 95%CI1.088-3.108)and prior pregnancy(P=0.042, OR=5.258, 95%CI1.062-26.038)are associated with the production of anti-HLA class Ⅰ and class Ⅱ antibodies, respectively. The time from disease diagnosis to antibody testing≥41 days(P=0.000, OR=2.873, 95%CI1.612-5.119), initial platelet count<20×10⁹/L(P=0.008, OR=2.164, 95%CI1.225-3.822), prior pregnancy(P=0.002, OR=6.734, 95%CI1.993-22.751), transfusions before admission(P=0.001, OR=2.746, 95%CI1.531-4.925)and total platelet transfusion volumes after admission>30 U(P=0.006, OR=3.459, 95%CI1.416-8.451)are associated with the production of anti-HLA class Ⅰ and Ⅱ antibodies. 【Conclusion】 Older age, longer course of disease, lower PLT count, history of pregnancy and blood transfusion, and higher total amount of PLT transfusion are risk factors which affect the production of anti-HLA antibodies.Therefore, it is advisable to test for anti-HLA antibodies according to the situation before transplantation, which is of great value in guiding donor selection, monitoring antibody changes and improving transplant prognosis.

Objective To explore the utility of different endoscopic retrograde cholangiopancreatography(ERCP)complexity scales in the training of endoscopists.Methods Clinical data of 237 patients treated by ERCP completed by trainee physicians at two hospitals in Eastern China from February 2022 to February 2023 were prospectively collected.All ERCP cases were classified using previously proposed complexity grading scales,including the American Society of Gastrointestinal Endoscopy(ASGE),Morriston and HOUSE grading scales,compared with the hepatopancreatic ampulla features classification.Successful intubation,successful surgical treatment and complication rates within 48 h were recorded.Results Within each grading,subgroups were divided according to severity,and the comparison of intubation success rates between subgroups in the 3 different grades showed statistically significant differences(P = 0.000).The treatment success rate and intubation success rate had similar findings(P = 0.000).There was no correlation between the complication rate and ASGE grading(P = 0.361),Morriston grading(P = 0.332),and HOUSE grading(P = 0.586).When only cases with primitive papillae were considered,the intubation success rate depended on the complexity grading after the newly added classification of hepatopancreatic ampulla features.In the ASGE group,the success rate of intubation was compared between different subgroups,and the difference was statistically significant(P = 0.004);in the Morriston group,the success rate of intubation was compared between different subgroups,and the success rate of intubation was statistically significant(P = 0.002);in the HOUSE group,the success rate of intubation was compared between different subgroups,and the difference was statistically significant(P = 0.000);In the hepatopancreatic ampulla characteristics group,the difference in intubation success rate was statistically significant when compared between different subgroups(P = 0.000).Similar findings were also found for treatment success rate and intubation success rate(P = 0.000).There was no correlation between the complication rate and ASGE group(P = 0.586),Morriston group(P = 0.443),HOUSE group(P = 0.306),and hepatopancreatic ampulla characteristics group(P = 0.350).Conclusion The use of hepatopancreatic ampulla features as a classification of biliary cannulation complexity is feasible and could be an alternative or additional means of predicting successful biliary cannulation and surgical treatment success and could be used in the future to assess endoscopist training and learning progress and technical standards.

AIM:To investigate the effects of ginkgetin on neurological deficit and angiogenesis induced by cerebral ischemia/reperfusion(I/R)and its underlying mechanism.METHODS:Sixty SD rats were randomly allocated into three groups:sham group,I/R model group,and ginkgetin(40 mg/kg)treatment(I/R+ginkgetin)group,with twenty rats in each group.The middle cerebral artery occlusion/reperfusion(MCAO/R)rat model was employed to simulate cere-bral I/R,and ginkgetin was administered continuously for 7 days following reperfusion.The cerebral infarction volume was quantified using TTC staining.Neuronal density in the ischemic penumbra was assessed through Nissl staining and immu-nohistochemistry for neuron-specific nuclear protein(NeuN).Microvessel density and angiogenesis in the ischemic pen-umbra of each group were analyzed using CD31 labeling and BrdU/von willebrand factor(vWF)double labeling immuno-fluorescence staining.Western blot analysis was performed to determine the levels of heat shock protein 70(HSP70),vas-cular endothelial growth factor(VEGF),and hypoxia inducible factor-1α(HIF-1α)in the ischemic penumbra.RE-SULTS:Compared with the I/R model group,the cerebral infarction volume was significantly reduced in ginkgetin treat-ment group(P<0.01),the number of neurons,the microvessel density,angiogenesis and the expression levels of HIF-1α,VEGF,and HSP70 in the ischemic penumbra were significantly increased(P<0.01).CONCLUSION:Ginkgetin exhibits the potential to augment angiogenesis and facilitate neurological function recovery in MCAO rats,while concur-rently upregulating the expression of HSP70,VEGF,and HIF-1α within the ischemic penumbra.

Objective:To determine the relationship between health self-empowerment level and health self-management skill in older adults.Methods:A household survey was conducted from June 2020 to April 2021, among older adults in two communities each in Zhuzhou and Changsha selected by stratified cluster sampling. Data were collected through a general questionnaire, simplified. Elders Health Empowerment Scale, and Rating Scale of Health Self-Management Skill for Adults. A total of 444 questionnaires were distributed, of which 425 were valid. Pearson correlation and hierarchical regression analyses were used to analyze the relationship between health self-empowerment level and health self-management skill.Results:Final sample included 425 elderly people. Health self-empowerment was at medium to high level (30.9±5.6), whereas health self-management was at medium level (146.2±21.7); and the two factors were significantly correlated (Pearson coefficient was 0.724). After controlling for confounding factors (demographic characteristics), health self-empowerment independently accounted for 34.3% of the variation in health self-management ability.Conclusion:Health self-empowerment positively affects health self-management ability among older adults, which suggests the importance of stimulating health self-empowerment awareness in the process of health self-management.

Objective:To investigate the molecular mechanism of sorafenib against hepatocellular carcinoma.Methods:Sorafenib efficacy was screened and verified by the hepatocellular carcinoma patient-derived tumor xenograft (PDX) model. Veterinary B-mode ultrasonography and in vivo confocal laser scanning microscopy were used to observe PDX angiogenesis. Immunohistochemistry was used to observe the expression of proliferation and angiogenesis-related proteins in PDX tissue. Real-time quantitative PCR technology was used to observe the RUNX3 gene in PDX tissues. SPSS 17.0 statistical software was used for statistical analysis.Results:Four cases of PDX were used to screen the efficacy of sorafenib. PDX1 had a significant response to sorafenib, with an inhibition rate of 68.07%. Compared with the control group, sorafenib had significantly inhibited PDX1 relative tumor volume (5.76±2.14 vs. 11.71±2.87, P<0.05). Cell division index (39.50±7.72 vs. 67.10±9.14, P<0.05) and Ki67 expression (288.6±43.40 vs. 531.70±55.60, P<0.05) were significantly decreased. Veterinary B-mode ultrasonography showed evident blood flow signals in PDX1 tumors. In vivo confocal laser scanning microscopy results showed that sorafenib had significantly reduced the total vessel length (1573.00±236.21 vs. 2675.03±162.00, P<0.05) and area (11 145.33±1931.97 vs. 20 105.37±885.93, P<0.05)) of PDX1 tumors. Immunohistochemical results showed that sorafenib had significantly down-regulated the protein expressions of CD34 (27.55±3.76 vs. 45.47±5.57, P<0.05), VEGF (16.33±2.86 vs. 22.77±3.20, P<0.05) and MVD (38.75±6.01 vs. 55.50±8.61, P<0.05). Real-time PCR results showed that sorafenib had significantly up-regulated RUNX3 gene expression (2.14±0.71 vs. 1.00±0.36, P<0.05). However, there was a negative correlation between the expression of RUNX3 gene and the ratio of VEGF-positive cells in sorafenib group ( R2=0.509 7). Conclusion:Sorafenib may inhibit the PDX angiogenesis and the growth of hepatocellular carcinoma by regulating the RUNX3-VEGF pathway.

The research on human hepatobiliary development and disorders has been constrained by minimal access to human fetal tissue, and low accuracy of animal models. To overcome this problem, we have established a system for the differentiation of human pluripotent stem cells (hPSCs) into functional hepatobiliary organoids (HBOs). We have previously reported that our 45-d approach closely mimics key stages of hepatobiliary development, starting with the differentiation of hiPSC into endoderm and a small part of mesoderm, and subsequently into hepatoblast-like cells, followed by the parallel generation of hepatocyte-like cells and cholangiocyte-like cells, formation of immature HBO expressing early hepatic and biliary markers, and mature HBO displaying hepatobiliary functionality. In this study, we present an updated version of our previous protocol, which only needs 35 days to achieve maturation in vitro. Furthermore, a hepatobiliary culture medium is developed to functionally maintain the HBOs for more than 1.5 months. The capacity of this approach for producing large amounts of functional HBOs and enabling long-term culture in vitro holds promise for applications on developmental research, disease modeling, as well as screening of therapeutic agents.

Objective:Establish the decision threshold value of mean fluorescence intensity of anti-human leukocyte antigen(HLA)antibody through statistical analyzing the results of international proficiency testing(PT)organized by American Society for Histocompatibility and Immunogenetics(ASHI).Methods:Single antigen reagent and liquid chip(Luminex)technique were used to detect anti-HLA antibody. A retrospective analysis of the HLA antibody PT results of 55 quality control samples from 11 times organized by ASHI from 2012 to 2019 was reviewed.Results:Among 79 kinds of HLA-I antibodies, 21, 43 and 15 types of HLA-A, B and Cw antibodies were detected respectively, while among 44 kinds of HLA-Ⅱ antibodies, 18, 7 and 19 types of HLA-DRB1, DQB1 and DPB1 antibodies were detected respectively. After analyzing the MFI detection value of different specific antibodies in each PT samples at our laboratory and the coincidence rate of the negative / positive results judged by ASHI through summarizing the results of multicenter participating in the same period, MFI values of HLA antibody were arranged from high to low into the intervals of possible saturation value, positive decision value, positive judgment threshold value, suspicious positive reference value and suspicious negative reference value , according to the coincidence rate of 95%, 90%, 80%, 79%~50% and <50%.Thus, the decision limit value table of HLA specific antibody at our laboratory was established. And 42 kinds of HLA antibody types were detected with complete data.When the MFI values of various HLA-I or HLA-Ⅱ antibodies are found to be 80% or more in the table, it can be used to judge the detection of HLA antibodies. When HLA antibody MFI value reaches the positive decision value, it may have a certain guiding significance for clinical diagnosis and treatment. And when antibody MFI value reaches the saturation value and lies in the suspicious positive or suspicious negative reference threshold, it just suggests that the clinical need for dynamic follow-up of anti-HLA antibody detection.Conclusions:The decision limit value of MFI of laboratory HLA antibody is established based on the international PT experimental results, which is of reference value for the interpretation of experimental results and clinical diagnosis and treatment. A transplant ation center should pay attention to the quality control of comparison test between laboratories in the detection of HLA antibodies.

Objective:To analyze the clinical characteristics of patients with double-positive anti-myelin oligodendrocyte glycoprotein (MOG) antibody and anti-N-methyl-D-aspartate receptor (NMDAR) antibody, so as to raise awareness of such diseases and improve the prognosis.Methods:Eighteen patients (double positive group) with positive serum anti-MOG antibody and cerebrospinal fluid anti-NMDAR antibody in Huashan Hospital, Fudan University from March 2017 to March 2020 were retrospectively analyzed. Using the SPSS software for simple random sampling, anti-MOG group(20 cases) and anti-NMDAR group (20 cases) were randomly selected at the same time for comparison. The anti-MOG group referred to the patients only with positive serum anti-MOG antibody. While the anti-NMDAR group referred to the patients whose cerebrospinal fluid anti-NMDAR antibody was positive. The clinical characteristics, laboratory examination results, radiological characteristics and prognosis of the three groups were collected and analyzed.Results:There was no statistically significant difference in demographic data among the three groups ( P>0.05). The symptoms of patients in the double-positive group were divided into two categories by cluster analysis, which corresponded to the symptom groups obtained by cluster analysis of the anti-MOG group and the anti-NMDAR group, and the same result was verified by correspondence analysis. Compared with the anti-MOG group, the incidence of epilepsy (10/18 vs 3/20, P=0.016), psychosis and behavior change (8/18 vs 0/20, P=0.001), visual disturbances (8/18 vs 17/20, P=0.016), dysarthria/dysphagia (8/18 vs 1/20, P=0.007) was significantly different in the double-positive group ( P<0.017). Compared with the anti-NMDAR group, the incidence of ataxia (8/18 vs 19/20, P=0.001), psychosis and behavior change (12/18 vs 1/20, P<0.001) was significantly different in the double-positive group. There was no statistically significant difference in the combination rate of thyroid peroxidase antibody, thyroglobulin antibody and antinuclear antibody between two groups, and the cerebrospinal fluid pressure, white blood cell count, protein, glucose, chloride and positive rate of oligoclonal band were also not statistically different between two groups ( P>0.017; P<0.017 indicates statistically significant difference by Bonferroni corrected multiple comparisons). Compared with the anti-NMDAR group, whether the brain magnetic resonance imaging had lesions was different in double positive group (18/18 vs 8/20, P<0.001). The initial modified Rankin Scale (mRS) scores before treatment were different among the double positive group, anti-MOG group and anti-NMDAR group (3.72±0.96, 2.75±0.97, 3.95±0.76, respectively, F=10.004, P<0.001), but there was no statistically significant difference in the scores after six-month treatment (1.22±1.44, 0.40±0.75, 1.20±1.24, respectively, F=3.153, P=0.051), and the recurrence rate of the disease was different among the three groups (8/18, 14/20, 5/20, respectively, χ2=10.004, P=0.017). Conclusions:Anti-MOG antibodies and anti-NMDAR antibodies could exist at the same time, showing clinical phenotype overlap, which was a new syndrome called the overlapping syndrome of myelin oligodendrocyte glycoprotein antibody-associated disease and NMDAR encephalitis, MNOS. The condition of MNOS patients was more severe than that of patients with MOG antibody-associated disease (MOGAD), but patients with MNOS, MOGAD, and anti-NMDAR encephalitis all responded well to immunosuppressive therapy. It was suggested that early second-line immunotherapy should be given to reduce the recurrence rate in patients with MNOS and MOGAD.

Objective:To evaluate the biomechanical behaviors of different framework materials in implant-supported fixed mandibular prosthesis using three-dimensional finite element analysis.Methods:A model of implant-supported fixed mandibular prosthesis was established. The simulations were divided into six groups according to the framework materials: pure titanium, cobalt-chromium alloy, gold alloy, zirconia, polyether ether ketone (PEEK) and carbon fiber-reinforced PEEK. An oblique load of 300 N with a 75° angle to the occlusal plane was applied from the lingual side on the buccal cusps of the two premolars and the first molar teeth. The stresses on implants, surrounding bones and frameworks were analyzed and compared among the framework materials both quantitatively and qualitatively.Results:In implant-supported fixed mandibular prosthesis model, the highest stresses were located around the neck of the implants and cortical bone during oblique loading among six designs. In addition, the stresses were concentrated on the buccal and distal cortical bone around the implants of the posterior region. Stress values of implants and cortical bones from low to high were as follows: zirconia, cobalt-chromium alloy, pure titanium, gold alloy, carbon fiber-reinforced PEEK, PEEK. The von Mises stress values of implant and cortical bone in the first molar site of PEEK framework material were 44.96 and 29.13 MPa, while the von Mises stress values of implant and cortical bone in the first molar site of zirconia framework material were 21.29 and 17.79 MPa. The zirconia and medal framework materials were more advantageous in stress distribution around implants than PEEK framework material.Conclusions:In implant-supported fixed mandibular prostheses, biomechanical analysis showed that the zirconia and medal framework materials were more advantageous in stress distribution around implants than PEEK framework materials.

Alzheimer′s disease (AD) is an incurable disease in the field of major chronic diseases. Subjective cognitive decline (SCD) is a clinical risk factor for AD. The standardized screening and intervention in individuals with SCD are of great importance in early prevention and treatment of AD. According to the clinical criteria proposed by The characterisation of subjective cognitive decline, which was published online in Lancet Neurology, the article summarized the definition of SCD, the latest perspective of clinical standards in SCD, and the results of AD preclinical SCD research. The purpose of this work was to provide concrete guidance and recommendations for making clinical decisions in diagnosis and scientific research on SCD.