Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C / 药物分析学报

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Development of a CLDN18.2-targeting immuno-PET probe for non-invasive imaging in gastrointestinal tumors / 药物分析学报

Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-89(89Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[89Zr]Zr-des-ferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,＞99％)and specific activity(24.15±1.34 GBq/μmol),and was stable in 5％human serum albumin,and phosphate buffer saline(＞85％RCP at 96 h).The EC50 values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P＞0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[89Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2(-).The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16％ID/g)than BGC823 mice(0.69±0.02％ID/g)and blocking group(0.72±0.02％ID/g).A dosimetry estimation study showed that the effective dose of[89Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these re-sults suggest that Good Manufacturing Practices produced by this immuno-positron emission tomog-raphy probe can detect CLDN18.2-overexpressing tumors.

Guijiajiao (Colla Carapacis et Plastri, CCP) prevents male infertility via gut microbiota modulation / 中国天然药物

Male infertility is a significant cause of psychosocial and marital distress in approximately 50% of couples who are unable to conceive, with male factors being the underlying cause. Guijiajiao (Colla Carapacis et Plastri, CCP) is a Traditional Chinese Medicine commonly used to treat male infertility. The present study aimed to investigate the potential mechanisms underlying the preventive effects of CCP on male infertility. An infertile male rat model was established using cyclophosphamide (CTX), and CCP was administered for both treatment and prevention. Fecal microbiota transplantation (FMT) was also performed to explore the role of gut microbiota in the CCP-mediated prevention of male infertility in rats. Sperm motility and concentration were determined using a semi-automatic sperm classification analyzer. Subsequently, histopathological analysis using HE staining was performed to examine the changes in the small intestine and testis. Moreover, the serum levels of lipopolysaccharide (LPS) and testosterone were measured by ELISA. In addition, immunohistochemistry was conducted to detect CD3 expression in the small intestine, while RT-qPCR was employed to assess the expressions of interleukin-1 beta (IL-1β), cluster of differentiation 3 (CD3), Monocyte chemoattractant protein-1 (MCP-1), and C-X-C motif chemokine ligand 10 (CXCL-10) in the small intestine and epididymis. Finally, gut microbiota was analyzed by 16S rRNA sequencing. CCP improved sperm motility, number, and concentration in CTX-induced infertile male rats. CCP increased the serum testosterone level, inhibited the immune cell infiltration of the intestinal lamina propria, and promoted the aggregation of CD3+ T cells in CTX-induced male infertility rats. CCP also inhibited the expressions of MCP-1, CXCL-10, and IL-1β in the epididymis of male infertility rats. At the genus level, CTX led to a reduction in the abundance of Lactobacillus, Clostridia_UCG.014, and Romboutsia in the intestinal tract of rats. In contrast, CCP decreased the abundance of Ruminococcus and increased the abundance of Romboutsia in infertile male rats. Additionally, FMT experiments proved that the gut microbiota of CCP-treated rats facilitated testicular tissue recovery and spermatogenesis while also reducing the serum LPS level in infertile male rats. CCP improves the spermatogenic ability of infertile male rats by restoring gut microbiota diversity and inhibiting epididymal inflammation.

Dihydromyricetin improves Parkinson's disease-like lesions in T2DM rats by activating AMPK/ULK1 pathway / 生理学报

The purpose of this study was to explore the effect and mechanism of dihydromyricetin (DHM) on Parkinson's disease (PD)-like lesions in type 2 diabetes mellitus (T2DM) rats. The T2DM model was established by feeding Sprague Dawley (SD) rats with high-fat diet and intraperitoneal injection of streptozocin (STZ). The rats were intragastrically administered with DHM (125 or 250 mg/kg per day) for 24 weeks. The motor ability of the rats was measured by balance beam experiment, the changes of dopaminergic (DA) neurons and the expression of autophagy initiation related protein ULK1 in the midbrains of the rats were detected by immunohistochemistry, and the protein expression levels of α-synuclein (α-syn), tyrosine hydroxylase (TH), as well as AMPK activation level, in the midbrains of the rats were detected by Western blot. The results showed that, compared with normal control, the rats with long-term T2DM exhibited motor dysfunction, increased α-syn aggregation, down-regulated TH protein expression, decreased number of DA neurons, declined activation level of AMPK, and significantly down-regulated ULK1 expression in the midbrain. DHM (250 mg/kg per day) treatment for 24 weeks significantly improved the above PD-like lesions, increased AMPK activity, and up-regulated ULK1 protein expression in T2DM rats. These results suggest that DHM may improve PD-like lesions in T2DM rats by activating AMPK/ULK1 pathway.

Serotypes and drug resistance of salmonella in commercial food in Pudong New Area from 2020 to 2022 / 上海预防医学

ObjectiveTo understand the serotype distribution and drug resistance of salmonella contaminated in commercially available food. MethodsSalmonella detection， including the serotypes， was conducted in food products sold in Pudong New Area from 2020 to 2022. The antimicrobial susceptibility test of 15 antibiotics was conducted by the broth microassay. ResultsA total of 118 salmonella strains were detected in 2 497 pieces of food， with a total detection rate of 4.7%. The dominant detection categories were poultry meat， livestock meat and aquatic products. The 118 salmonella strains could be divided into 24 serotypes， Salmonella enteritidis （26.4%）， Salmonella Typhimurium （16.2%） and Salmonella delpy （14.4%） were the main dominant types. Salmonella had the highest resistance rate to ampicillin （63.6%）， followed by tetracycline， chloramphenicol， cotrimoxazole and nalidixic acid. Among the three dominant serotypes， the multidrug resistance rate of Salmonella typhimurium was the highest （89.5%）， followed by Salmonella delpy （70.6%） and Salmonella enteritidis （61.3%）. ConclusionLivestock， poultry meat， and aquatic products are seriously contaminated by salmonella with diverse serotypes. The livestock meat is mainly contaminated by Salmonella typhimurium and Salmonella delpy， and the poultry meat is mainly contaminated by Salmonella enteritidis. The drug resistance spectrum is wide and the multi-drug resistance rate is high. Different from the livestock and aquatic isolates， poultry meat-derived strains have high tolerance to ampicillin， nalidixic acid and polymyxin， and carry certain potential food safety risks.

Determination of suspended erythrocyte volume range and establishment of its internal control standard / 中国输血杂志

【Objective】 To determine the volume range of suspended erythrocyte and establish its internal control standard. 【Methods】 The theoretical value of suspended erythrocyte volume was calculated according to the screening criteria of healthy blood donors and Quality Requirements for Whole Blood and Blood Components. A total of 2 410 bags of 1 U and 2 U suspended erythrocyte were randomly selected and weighed, and the volume range were formulated by ±2S and ±10% respectively and then compared to determine the volume range in line with the actual situation of our center. 【Results】 The theoretical volume range of 1 U and 2 U suspended erythrocyte were 117-160 mL vs 234-320 mL, and the actual volume range were 142-180 mL vs 276-393 mL. The volume range of 1 U and 2 U suspended erythrocyte formulated by ±2S were 145-181 mL vs 298-358 mL, and by ±10% were 147-179 mL vs 295-361 mL. The hematocrit and hemoglobin content of suspended erythrocyte within the actual volume range met the quality requirements. There were fluctuations in the volume of suspended erythrocyte from different regions. 【Conclusion】 Based on the actual situation of our center and the sampling results of suspended erythrocytes in recent two years, 163 mL±10% and 328 mL±10% were determined as the internal control standards of 1 U and 2 U suspended erythrocyte, respectively. Blood centers should establish accurate and feasible standard of suspended erythrocyte according to the actual situation.

Analysis of related factors of plasma antibody titer in convalescent patients with COVID-19 / 中国输血杂志

【Objective】 To study the relationship between the plasma IgG, IgM, neutralizing antibody titer and sex, age, collection interval in convalescent patients with COVID-19, so as to guide the plasma collection of convalescent patients with COVID-19. 【Methods】 COVID-19 convalescent plasma was collected to determine the antibody titer, and the difference and correlation of data in each group were analyzed by SPSS statistical analysis software. 【Results】 The median titers (AU/mL)of IgG, IgM and neutralizing antibodies in males and females were 484.24 vs 516.04, 2.13 vs 1.73, and 1 124.74 vs 1 143.99, respectively, and there was no significant difference(P>0.05) . Age had weak positive correlation with IgG and neutralizing antibody, and the Spearman correlation coefficient was 0.188 (P<0.05). The median titers (AU/mL) of IgG, IgM and neutralizing antibody at first donation of 30 repeated donors were 522.3, 2.64 and 1 174.6, respectively, but at second donation were 332.08, 0.63 and 708.96, showing significant difference (P<0.05). 【Conclusion】 There was no significant difference in the plasma IgG, IgM and neutralizing antibody titers in convalescent COVID-19 patients of different ages and genders, and the titers met the requirements of clinical treatment guidelines. Although the plasma antibody level of repeated donors has decreased, it still has clinical value.

Risk factors affecting the prognosis of sepsis patients with blood transfusion / 中国输血杂志

【Objective】 To explore the factors affecting the prognosis of sepsis patients with blood transfusion, and provide safe and scientific blood transfusion recommendations for them. 【Methods】 The clinical data of 134 sepsis patients in our hospital from January 2018 to June 2021 were collected through retrospective analysis, and divided into the blood transfusion group (n=45) and non-transfusion group (n=89) according to whether they received transfusion or not. The basic clinical data and laboratory indicators of two groups were compared. According to the survival outcome and the occurrence of septic shock, patients in the blood transfusion group were subdivided into death group (n=17) and survival group (n=28), shock group (n=12) and non-shock group (n=33). Logistic regression analysis was used to analyze the risk factors that affect the survival outcome of septic patients after blood transfusion and the occurrence of septic shock. 【Results】 Statistical differences were noticed inblood transfusion group and the non-transfusion group by Hb (71.4±15.7 vs 100.6±21.9) g/L, PCT (13.7±27.2 vs 6.7±18.1) ng/mL, CRP (80.4±81.9 vs 46.6±67.1) mg/mL, APTT (43.4±22.6 vs 33.3±12.8) s, Fib (3.0±1.7 vs 4.0±1.7) g/L, LAC (3.4±4.2 vs 1.9±2.7) mmol/L, length of hospital stay (20.6±18.7 vs 14.1±10.9)d, and survival outcomes (P<0.05). Multivariate logistic regression analysis showed that red blood cell storage days (OR=0.183) and patient Hb level (OR=0.034) were risk factors that affected the survival outcome of sepsis patients after blood transfusion (P<0.05). 【Conclusion】 Compared with the non-blood transfusion group, the patients in the blood transfusion group had longer hospital stays, and different survival outcomes. The red blood cell storage days and Hb level of patients were the risk factors affecting the survival outcome of sepsis patients after blood transfusion, and RBCs with shorter storage period were suggested for sepsis patients.

Detection and analysis of neutralizing antibodies against SARS-CoV-2 in convalescent plasma donors / 中国输血杂志

【Objective】 To detect the anti-SARS-CoV-2 neutralizing antibody levels in convalescent plasma (CP) and to evaluate whether it has specific anti-SARS-CoV-2 S antigen effect, so as to provide laboratory data support for clinical use of CP. 【Methods】 Nine CP donors who have recovered from COVID-19 were studied, and 4 volunteers who completed the vaccination and 3 asymptomatic infected blood donors were compared. Anti-SARS-CoV-2 antibodies including total antibody, IgM and IgG were measured by chemiluminescence microparticle immunoassays (CMIA) test in three groups. The VSV pseudovirus-based neutralization assay for evaluating neutralizing antibodies against SARS-CoV-2 was carried out in all samples. 【Results】 All samples were tested positive by the total antibody and IgG CMIA in COVID-19 CP donors and recipients of inactivated COVID-19 vaccine. High titers of IgG were observed in CP donors and vaccine recipients compared with asymptomatic blood donors. All vaccine recipients and 8 of 9 CP donors tested positive by SARS-CoV-2 pseudovirus-based neutralization test, whereas all asymptomatic blood donors tested negative. 【Conclusion】 The levels and characteristics of neutralizing antibodies among COVID-19 CP donors, vaccine recipients and asymptomatic blood donors were different. When unable to implement the pseudovirus assay to measure neutralizing antibodies, the detection of total antibody can be considered instead.

Determination of methylene blue release in plasma virus inactivation bag by fluorescence energy transfer method / 中国输血杂志

【Objective】 To establish a simple, economical and rapid method for the determination of methylene blue (MB) release in virus inactivation bag. 【Methods】 Based on the fluorescence energy transfer between MB and BSA-stabilized gold nanoclusters (BSA-AuNCs), the standard curve of MB determination was established by measuring the fluorescence quenching degree of MB to BSA-AuNCs in different concentrations to conduct the determination of MB release in virus inactivation bag. 【Results】 There was a good linear relationship between the MB concentration (cMB) and the fluorescence quenching degree of BSA-AuNCs[ (I0-I)/I0=0.018cMB+ 0.021(r=0.996)] when the fluorescence emission wavelength was about 620 nm and the cMB was in the range of (0.9-36) μmoL/L. The recovery of MB was 98.00% -101.95 % when applied to determine MB at high, medium, and low concentrations, the obtained intra-day variation coefficients were 0.73%, 0.81% and 0.77% respectively, and the obtained inter-day variation coefficients were 3.92%, 3.81%, and 4.73% respectively. There was no significant difference between the results measured by this method and those measured by combination of solid-phase extraction and spectrophotometry(P>0.05). 【Conclusion】 The fluorescence energy transfer method could achieve simple and rapid determination of MB release in virus inactivation bag with accurate and reliable results.

Determination of fibrinogen content in cryoprecipitated antihemophilic factor by fluorescence quenching method / 中国输血杂志

【Objective】 To establish a new method for the determination of fibrinogen content in cryoprecipitated antihemophilic factor. 【Methods】 Fibrinogen (Fib) could bind with sheep anti-human fibrinogen (anti-Fib) specifically and further form antigen-antibody complex. When the Fib was present in the solution, the fluorescence of fluorescein isothiocyanate (FITC) labeled on the anti-Fib (FITC-anti-Fib) was quenched due to the formation of immune complex. The fluorescence quenching degree of FITC-anti-Fib was positively correlated with Fib concentration (cFib) in a certain concentration range. 【Results】 The linear relationship between fluorescence quenching degree [(I0-I)/I0] of FITC-anti-Fib and ln(cFib) was (I0-I)/I0=15.53ln(cFib)+ 80.79 (R2=0.99) when the cFib was in the range of (0.007 8-0.560 0) g/L. The recovery of Fib was (96.77-102.43) %. When the method was applied to determine Fib at high, medium, and low concentrations, the obtained intra-day variation coefficients were 0.31%, 0.56%, and 0.49%, respectively, and the inter-day variation coefficients were 3.81%, 3.06%, and 4.13%, respectively. There was no significant difference between the results measured by fluorescence quenching method and coagulation method (t=-0.075, P>0.05). 【Conclusion】 In this work, a new fluorescence method for the determination of Fib in cryoprecipitated antihemophilic factor was successfully established based on the specific combination of fib and FITC-anti-Fib. The method is simple and rapid. The obtained results were accurate and reliable by using this method to determine Fib.

Clinical analysis of 252 patients with tuberculous peritonitis in Wuhu area / 中华临床感染病杂志

Objective:To analyze the clinical features of tuberculous peritonitis (TBP).Methods:The clinical data of 252 TBP patients admitted to three hospitals in Wuhu area from January 2014 to June 2020 were retrospectively analyzed, and the clinical characteristics of TBP patients of different genders and ages were compared. SPSS 26.0 software was used to analyze the data.Results:Among 252 TBP patients, 130 were males (51.6%) and 122 were females (48.4%). History of abdominal surgery, abdominal masses, reproductive disorders, genital tuberculosis, and delay in diagnosis were more common in female patients (all P<0.01); while fever, cough/sputum expectoration, intestinal tuberculosis and active tuberculosis were more common in male patients (all P<0.01). The proportion of adenosine deaminase in ascites (ADA) ≥35 U/L, strong positive tuberculin test or T-cell spot test in middle-aged and elderly patients was lower than that in young patients ( P<0.01), but there was no significant difference between different genders. Compared with young patients, middle-aged and elderly patients had a low complete response rate, a high proportion of irregular medications, a high incidence of gastrointestinal reactions, liver damage and overall adverse reactions (all P<0.05). Conclusion:Female patients with TBP have fewer symptoms of systemic tuberculosis and high rate of delay in diagnosis, and are prone to complicated with reproductive tuberculosis. In middle-aged and elderly patients with TBP, the sensitivity of ADA and tuberculosis tests is decreased, and the anti-tuberculosis therapy is less effective. The study indicates that the clinical diagnosis and treatment of TBP should be optimized based on the gender and age of patients.

Preparation and tumor-specific molecular imaging of a novel PET probe targeting angiotensin converting enzyme 2 / 中华核医学与分子影像杂志

Objective:To prepare a novel molecular imaging probe targeting angiotensin converting enzyme (ACE) 2 by using 68Ga labeled with 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-DX600, then the probe was evaluated in cervical cancer model by microPET/CT imaging. Methods:68Ga labeled DOTA-DX600 at 95 ℃, and the quality control, stability in vitro and lipid-water partition coefficient (log P) were tested. Tumor-bearing mouse models were constructed using stably transfected ACE2 highly expressed cervical cancer cells (Hela). The distribution and uptake of 68Ga-DOTA-DX600 in normal KM mice and tumor-bearing mice were determined by microPET/CT imaging, and the maximum standardized uptake value (SUV max) of the main organs and tumors were obtained by semi-quantitative analysis of the region of interest (ROI). Results:The preparation time of 68Ga-DOTA-DX600 was about 20 min, the specific activity of the probe was (18.74±3.72)×10 6 GBq/mol, the labeling rate was 82.3%, and the radiochemical purity was about 99% after purification. After placement in saline or 5% human serum albumin (HSA) solution at room temperature for 2 h, the radiochemical purity of the probe was more than 96%. The lipid-water partition coefficient (log P) was -2.44 ±0.04 ( n=3), which indicated as a good hydrophilicity. In normal KM mice, 68Ga-DOTA-DX600 metabolized faster in the blood and mainly distributed in the kidneys. The probe showed good tumor targeting ability in the tumor-bearing mice and the SUV max of the tumor were 0.25±0.01 and 0.21±0.01 at 30 min and 60 min after injection, respectively, and the tumor uptake was inhibited by DX600. Conclusion:68Ga-DOTA-DX600 can be obtained conveniently and fast and shows a good targeting ability to tumors, which provide potential application value for researches on targeting ACE2.

Related quality indexes of different common plasma products: A comparative study / 中国输血杂志

【Objective】 To explore the difference of total protein (TP) content, coagulation factor VIII (FⅧ) activity and Fib content in different common plasma products, and to further provide basis for the establishment and refinement of relevant quality standards of common plasma products. 【Methods】 Samples involved in the experiment included frozen plasma and cryoprecipitated frozen plasma derived from whole blood and eukocyte-depleted whole blood. The TP content determination was carried out by biuret method. The FⅧ activity (FⅧ: C) and Fib content were determined by coagulation method. 【Results】 The TP content( g/L) in frozen plasma and cryoprecipitated frozen plasma derived from whole blood and eukocyte-depleted whole blood were 59.64±4.78 vs 58.09±4.1 vs 52.20±3.57 vs 51.89±1.50, respectively, and the FⅧ: C( %) were 109.63±43.38 vs 27.06±7.09 vs 71.83±21.64 vs 21.66±3.86,, and the Fib content (g/L) were 2.19±0.39 vs 1.30±0.24 vs 2.04±0.37 vs1.22±0.15, respectively. There was a significant difference in TP content between other common plasma products (P0.05). There was significant difference in FⅧ: C among four common plasma products (P0.05). 【Conclusion】 The TP content and FⅧ: C of common plasma products are closely related to the initial blood and preparation process. It is suggested that the quality standard of common plasma products should be further refined, and the establishment of cryoprecipitated frozen plasma relevant quality standard and clinical indications should be considered.

SARS-CoV-2 seroprevalence among voluntary blood donors: A retrospective analysis in Xi′an / 中国输血杂志

【Objective】 To estimate the seroprevalence of SARS-CoV-2 infection among blood donors during the COVID-19 outbreak, in order to provide reference for formulating coping strategies. 【Methods】 A total of 3 623 samples of healthy blood donors in Xi′an from January 1 to June 14, 2020 were collected and tested by chemiluminescence microparticle immunoassays(CMIA). The correlation between the number of confirmed cases of COVID-19 in Xi′an and the monthly prevalence trend of SARS-CoV-2 antibody in Xi′an was also studied. 【Results】 Among the 3 623 blood donors, 3 were reactive by CMIA, with the seroprevalence rate of SARS-CoV-2 at 0.083%(95%CI: 0.00, 0.18). The earliest yielding of SARS-CoV-2 in Xi′an was in February 4, 2020. 【Conclusion】 The SARS-CoV-2 seroprevalence rate in Xi′an is low, which is in line with the local prevalence status. It is suggested that serological detection of blood donors is a way to monitor the prevalence of COVID-19.

Production and purification of solid target PET nuclide 89Zr and its antibody labeling / 中华核医学与分子影像杂志

Objective:To produce the solid target nuclide 89Zr , and prepare the probe 89Zr-desferrioxamine (DFO)-Trastuzumab. Methods:The 89Y(p, n) 89Zr nuclear reaction was used for 89Zr production. 89Y target was irradiated by 20 μA proton in a medical cyclotron ( E=12.5 MeV) for about 1-2 h. 89Zr was purified from hydroxamate resin using 1 mol/L oxalic acid solution. The characteristic peak, radionuclide purity and radiochemical purity of 89Zr were determined by γ-ray spectroscopy. 89Zr-DFO-Trastuzumab probe was synthesized by the reaction of 89Zr-oxalate and DFO-Trastuzumab at room temperature, and the radiochemical purity was measured. Results:89Zr was prepared successfully for 11 times, and the production of 89Zr was 555-1 506 MBq, with production rate of (34.8±5.2) MBq·μA -1·h -1. After the purification (purification rate: 42%-87%), 227.2-991.6 MBq 89Zr was obtained, with the concentration of 1.0×10 6 MBq/L. The γ spectrum showed that the characteristic peak of 89Zr were 511 and 909 keV, and no impurities were found. The radionuclide purity and radiochemical purity were both close to 100%. 89Zr-DFO-Trastuzumab was successfully labeled with radiochemical purity more than 95%, and it was above 90% within 72 h in human serum albumin (HSA) solution. Conclusion:Through the self-designed target assembling, the solid target PET nuclide 89Zr with high quality and labeling are successfully achieved, which provides guarantee for the clinical application of the 89Zr drug.

Network Pharmacology Research of Wuzi Yanzongwan in Treatment of Male Infertility / 中国实验方剂学杂志

Objective:Exploring the material basis and mechanism of Wuzi Yanzongwan in the treatment of male infertility based on network pharmacology. Method:Traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP) was used to screen the active ingredients and targets in Wuzi Yanzongwan. GeneCards, OMIM and PharmGkb databases were used to screen the targets of male infertility. R language software was used to screen common targets of drugs and diseases, Pharmaceutical active ingredients-disease target interaction network was constructed by using Cytoscape software. The common target protein interaction network (PPI) was constructed by STRING platform, the gene ontology(GO) analysis of common target was analyzed by ClueGo plug-in, and Kyoto encyclopedia of genes and genomes(KEGG) pathway was enriched by R language software. Result:A total of 72 active ingredients were obtained from Wuzi Yanzongwan, and 35 possible targets for the treatment of male infertility were obtained. These targets are mainly involved in biological processes such as oxidation and antioxidant activity, and are mainly concentrated in phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) and hypoxia inducible factor-1(HIF-1) signaling pathways. Conclusion:The network pharmacology confirmed the multi-component, multi-target and multi-pathway action characteristics of Wuzi Yanzongwan, predicted the possible mechanism of Wuzi Yanzongwan in the treatment of male infertility, and provided theoretical basis for further study of its active ingredients and mechanism.

Comparison of the clinicopathological features between synchronous multiple early gastric cancer and single early gastric cancer / 中华消化杂志

Objective To investigate the clinicopathological features and correlation between synchronous multiple early gastric cancer (SMEGC)and single early gastric cancer (EGC).Methods From January 2008 to December 2016,the clinical data of 994 patients with EGC who underwent open or laparoscopic gastrectomy surgery were collected from the electronic medical data base of the First Affiliated Hospital of Nanjing Medical University and Xuzhou No.1 People's Hospital.The data of patients including gender,age,tumor morphologys,tumor location,tumor size,histological type,depth of invasion,lymph nodes metastasis,lymphovascular metastasis,peripheral nerve invasion,and blood types were analyzed.T test and Chi square test were used for statistical analysis.Results Among 994 EGC patients,27 cases (2.7％) were SMEGC,and 967 cases (97.3％) were single EGC.The percentage of male and female of single EGC were 71.4％ (690/967) and 28.6％ (277/967),respectively;the percentage of male and female of SMEGC were 88.9％ (24/27) and 11.1％ (3/27),respectively,and there was statistically significant difference in the gender composition ratio between single EGC and SMEGC (x2 =3.975,P=0.046).The incidence of ulcer in single EGC and SMEGC were 50.6％ (489/ 967) and 29.6 ％ (8/27),respectively,and the difference in the incidence of ulcers between single EGC and SMEGC was statistically significant (x2 =4.653,P=0.031).There were no statistically significant differences between single EGC and SMEGC in gross morphology,depth of invasion,lymph nodes metastasis,lymphovascular metastasis,peripheral nerve invasion,tumor location,pathological type and blood types (all P＞0.05).In the SMEGC patients,the incidence of main lesions invading the mucosa was 48.1％ (13/27) and submucosa invasion was 51.9％ (14/27);and for minor lesions,the corresponding incidences were 77.8％ (21/27) and 22.2％ (6/27),respectively,and the difference was statistically significant (x2 =5.063,P＜0.05).There were no statistically significant differences between the main lesions and minor lesions in tumor size,pathological type,with or without ulcers,gross morphology and tumor location (all P＞0.05).Conclusions The main risk factors of SMEGC are male and no ulcerative lesions.The clinicopathological features are similar between main lesions and minor lesions in SMEGC.

Therapeutic effects of silencing fibrinogen-like protein 2 gene on acute necrotizing pancreatitis mice / 中华胰腺病杂志

Objective To investigate the therapeutic effect of silencing fibrinogen-like protein 2 (FGL2) gene on acute necrotic pancreatitis (ANP) mice.Methods Eighteen C57/BL mice were randomly divided into SO (sham operation) group,ANP group and Ad-FGL2-siRNA group carrying FGL2 siRNA adenovirus,with 6 in each group.Sodium taurocholate was retrogradely injected into the biliopancreatic ducts of the mice to induce ANP mice model.The mice in Ad-FGL2-siRNA group were injected intravenously in the tail vein with Ad-FGL2-siRNA befor the model establishment.The mice were sacrificed 6 h later,and then the pancreatic tissue and blood were collected.TNF-α and IL-1β expression were measured with ELISA,pancreatic tissue was examined with routine pathological examination,FGL2 mRNA and protein expression were measured with reverse transcription-PCR,western blotting and immunohistochemical staining,and cell apoptosis was assessed by TUNEL method.Results The pathological score of the pancreatic tissue in SO group,ANP group and Ad-FGL2-miRNA group was(1.33 ±0.21),(9.17 ±0.98) and (6.26 ±0.52),respectively.The serum TNF-α level in SO group,ANP group and Ad-FGL2-miRNA group was(63.8 ± 4.2),(240.4 ± 18.6)and(123.0 ± 10.3)ng/L,respectively.The serum IL-1β level was (43.6 ±4.4),(186.6 ± 18.7)and (92 ±10.9)ng/L.The mRNA expressions of FGL2 was 1.20 ±0.22,4.40 ± 1.21 and 2.15 ± 0.56.The protein expressions of FGL2 was 0.33 ± 0.08,1.23 ± 0.24 and 0.68 ± 0.09.The rate of FGL2 positive cells was (2.56 ± 0.31) ％,(15.10 ± 3.23) ％ and (8.68 ± 1.81) ％.The number of apoptotic cells was (4.51 ±1.21),(35.81 ± 4.11) and (11.79 ± 3.02) / × 200HPF,which in the ANP group was higher than that in SO group,and in the Ad-FGL2-siRNA group was significantly lower than that in ANP group and higher than that in SO group.All the differences were statistically significant (all P values ＜ 0.05),except that on the FGL2 mRNA expression between Ad-FGL2-siRNA group and SO group.Conclusions Silencing FGL2 gene may alleviate pancreatic injury in ANP by reducing the release of inflammatory factors and inhibiting cell apoptosis.

Erectile dysfunction and psychological status in infertile males / 中华男科学杂志

Objective@#To investigate the relationship of erectile dysfunction (ED) with psychological factors in male patients with infertility.@*METHODS@#We conducted a questionnaire investigation among 252 male patients with infertility, which involved the general condition, results of semen routine examination, sexual life, and scores in IIEF-5, self-reported 9-item patient health questionnaire (PHQ-9) and 7-item generalized anxiety disorder scale (GAD-7). We analyzed the prevalence of ED, depression, and anxiety and their correlations among the patients in comparison with 100 fertile male controls.@*RESULTS@#In 245 of the infertility patients, the most common symptoms of depression and anxiety were "feeling tired or no vitality" and "easily getting worried or impatient", 20.4% of them with depression disorder and 42.9% with anxiety disorder. The PHQ-9 and GAD-7 scores were significantly higher in the infertile males than in the normal fertile controls (P <0.05), and so was the incidence of ED (28.6% vs 12.4%, P <0.05), while the IIEF-5 scores were markedly lower in the former than in the latter group (P <0.01), and so were sex frequency and sexual satisfaction (P <0.05). The PHQ-9 and GAD-7 scores were remarkably higher in the infertility patients with ED than in those without (P <0.01). Logistic regression analysis showed that the level of libido and results of semen routine examination were the risk factors for depression disorder, while age, education level, disease course and experience of assisted reproduction were those for anxiety disorder.@*CONCLUSIONS@#Male infertility patients have a poorer mental health and a higher incidence of ED than normal fertile men, and there is some interaction between psychological status and ED prevalence.