AIM:To investigate the value of combined detection of circulating cell-free DNA(cfDNA),a-fetal protein(AFP) and a L-fucosidase(AFU) for diagnosis of hepatocellular carcinoma(HCC).METHODS:Serum samples from 39 HCC pati...AIM:To investigate the value of combined detection of circulating cell-free DNA(cfDNA),a-fetal protein(AFP) and a L-fucosidase(AFU) for diagnosis of hepatocellular carcinoma(HCC).METHODS:Serum samples from 39 HCC patients and 45 normal controls were collected.Branched DNA(bDNA) was used to detect the level of cfDNA,and a receiver operating characteristic curve was employed to evaluate the diagnostic sensitivity,specificity,accuracy,positive predictive value,negative predictive value,positive likelihood ratio,negative likelihood ratio and Youden index,and to assess the diagnostic efficiency and their correlations with the clinicopathological features.AFP and AFU were detected by chemiluminescence and colorimetry,respectively.The significance of combined detection of the three biomarkers was discussed.RESULTS:cfDNA level was increased in 22 of the 39 HCC samples and in 2 of the 45 normal controls.cfDNA level in HCC samples was significantly higher than that in normal controls(P < 0.05).There were significant differences in sex and extra-and intrahepatic metastasis(P < 0.05).There was no significant correlation between cfDNA,AFP and AFU in the detection of HCC.The sensitivity of combined detection of cfDNA with one marker(AFP or AFU) and cfDNA with two markers(AFP and AFU) was 71.8%,87.2% and 89.7% vs 56.4%,53.8% and 66.7% for cfDNA,AFP and AFU used alone,respectively,the difference being statistically significant(P < 0.05).CONCLUSION:Quantitative analysis of cfDNA is sensitive and feasible,and the combined detection of cfDNA with AFP or AFU or both could improve the diagnostic sensitivity for HCC.展开更多
BACKGROUND Biliary diseases are common digestive system disorders which may combine with biliary tract infection such as cholecystitis or cholangitis.Thus,rapid identification of the bacteria and their antibiotic susc...BACKGROUND Biliary diseases are common digestive system disorders which may combine with biliary tract infection such as cholecystitis or cholangitis.Thus,rapid identification of the bacteria and their antibiotic susceptibility profiles are crucial for reducing the mortality of patients with biliary tract infection.AIM To identify bacterial species and antibiotic susceptibility for antibacterial therapy and analyze bile cultivation risk factors for increasing detection rates.METHODS This retrospective study was conducted from July 2008 to July 2017.In total,1339 bile samples which were collected during therapeutic endoscopic retrograde cholangiopan-creatography or percutaneous transhepatic cholangiodrainage or other biliary surgeries or biliary drainage were obtained to characterize pathogen spectra,antibiotic susceptibility,and clinical features.Clinical data including age,sex,comorbidities,clinical symptoms,protopathies,and history of biliary tract diseases and surgeries were collated from hospital medical records.Species identification and initial drug susceptibility were further identified by biochemical characterization using the VITEK 2 Compact test.RESULTS Positive microbiological findings were observed in 738 samples.The most frequently encountered strains were gram-negative bacteria(74.94%),including Escherichia coli(37.78%),Pseudomonas aeruginosa(8.96%),and Klebsiella pneumoniae(10.29%).Bile bacteria were largely sensitive to carbapenems,piperacillin/tazobactam,and gentamicin.Gram-negative strains had low susceptibility to ceftriaxone,quinolones and ampicillin.Almost the same microorganisms were present in patients with malignant and benign diseases.The number of samples with Klebsiella pneumoniae in the bile culture were significantly different between patients with malignant and benign diseases(55 vs 30;P=0.019).Age(P<0.001),fever(P<0.001),history of biliary tract diseases and surgeries(both P<0.001),benign disease(P=0.002),and the comorbidity chronic renal insufficiency(P=0.007)affected the positive rates of the bile samples.CONCLUSION Gram-negative bacteria were the most commonly isolated biliary bacteria.We determined the major factors associated with positive detection rates.Microbiological analysis of bile samples allowed accurate antibiotic treatments.展开更多
Live poultry markets（LPMs） are crucial places for human infection of influenza A（H7N9 virus）.In Yangtze River Delta,LPMs were closed after the outbreak of human infection with avian influenza A（H7N9） virus,and t...Live poultry markets（LPMs） are crucial places for human infection of influenza A（H7N9 virus）.In Yangtze River Delta,LPMs were closed after the outbreak of human infection with avian influenza A（H7N9） virus,and then reopened when no case was found.Our purpose was to quantify the effect of LPMs＇ operations in this region on the transmission of influenza A（H7N9） virus.We obtained information about dates of symptom onset and locations for all human influenza A（H7N9） cases reported from Shanghai,Jiangsu and Zhejiang provinces by May 31,2014,and acquired dates of closures and reopening of LPMs from official media.A two-phase Bayesian model was fitted by Markov Chain Monte Carlo methods to process the spatial and temporal influence of human cases.A total of 235 cases of influenza A（H7N9） were confirmed in Shanghai,Jiangsu and Zhejiang by May 31,2014.Using these data,our analysis showed that,after LPM closures,the influenza A（H7N9） outbreak disappeared within two weeks in Shanghai,one week in Jiangsu,and one week in Zhejiang,respectively.Local authorities reopened LPMs when there was no outbreak of influenza A（H7N9）,which did not lead to reemergence of human influenza A（H7N9）.LPM closures were effective in controlling the H7N9 outbreak.Reopening of LPM in summer did not increase the risk of human infection with H7N9.Our findings showed that LPMs should be closed immediately in areas where the H7N9 virus is confirmed in LPM.When there is no outbreak of H7N9 virus,LPMs can be reopened to satisfy the Chinese traditional culture of buying live poultry.In the long term,local authorities should take a cautious attitude in permanent LPM closure.展开更多
Objective： To investigate the effects of sleep electroencephalogram-modulated repetitive transcranial magnetic stimulation （SEM-rTMS） and conventional rTMS （C-rTMS） on the activity of hypothalamic-pituitary-adren...Objective： To investigate the effects of sleep electroencephalogram-modulated repetitive transcranial magnetic stimulation （SEM-rTMS） and conventional rTMS （C-rTMS） on the activity of hypothalamic-pituitary-adrenal （HPA） axis in patients with depression. Methods： In a double-blind, randomized controlled trial, 164 patients diagnosed with depression were randomized to treatment with SEM-rTMS （n=57）, C-rTMS （n=55） or sham rTMS （n=52） for 30 rain every day for 10 d. Before and after treatment plasma concentrations of adrenocorticotropic hormone （ACTH） and cortisol （CORT） were measured, and the 24-item Hamilton Depression Rating Scale （HAMD-24） was used for assessment. Results： The HAMD-24 scores and plasma ACTH and CORT concentrations of these depressive patients before treatment were significantly different from those of the normal control group （P〈0.05）. The HAMD-24 scores and plasma ACTH and CORT concentrations in the SEM-rTMS group and conventional rTMS group were decreased significantly （P〈0.05）. There was a significant positive correlation between the HAMD-24 scores and plasma ACTH （n=240, r=0.105, P=0.048） and CORT concentrations （n-240, r=0.126, P=0.023） in the patients with depression before and after treatment. Conclusion： The antidepressant effect of rTMS, including SEM-rTMS, may be related to its decreasing HPA axis activity. （This trail was registered. No： ChiCTR-TRC-00000465）展开更多
By using the density functional theory （B3LYP） and four highly accurate complete basis set （CBS-Q, CBS-QB3, CBS-Lq, and CBS-4M）ab initio methods, the X（C, N, O）-NO2 bond dissociation energies （BDEs） for CH3NO2...By using the density functional theory （B3LYP） and four highly accurate complete basis set （CBS-Q, CBS-QB3, CBS-Lq, and CBS-4M）ab initio methods, the X（C, N, O）-NO2 bond dissociation energies （BDEs） for CH3NO2, C2H3NO2, C2H5NO2, HONO2, CH3ONO2, C2H5ONO2, NH2NO2 （CH3）2NNO2 are computed. By comparing the computed BDEs and experimental results, it is found that the B3LYP method is unable to predict satisfactorily the results of bond dissociation energy （BDE）; however, all four CBS models are generally able to give reliable predication of the X（C, N, O）-NO2 BDEs for these nitro compounds. Moreover, the CBS-4M calculation is the least computationally demanding among the four CBS methods considered, Therefore, we recommend CBS-4M method as a reliable method of computing the BDEs for this nitro compound system.展开更多
Objective： To survey the special killing activity of CD3AK on anti-CEA-positive tumor enhanced by umbilical cord blood dendritic cell （DC） loaded with CEA recombinant vaccinia virus （CEA-rV）. Methods： Freshly is...Objective： To survey the special killing activity of CD3AK on anti-CEA-positive tumor enhanced by umbilical cord blood dendritic cell （DC） loaded with CEA recombinant vaccinia virus （CEA-rV）. Methods： Freshly isolated umbilical blood mononuclear calls （UBMC） were cultivated for 3 h. Suspension cells and attached calls were used to induce CD3AK calls and DC separately. DC was loaded with CEA-rV on the 3rd day to prepare CEA-rV＋DC. CD3AK cells were co-cultured with CEA- rV＋DC on the 8th day, to prepare CEA-rV＋DC＋CD3AK. The killing activity of each effector＇s cell, which included UBMC, CD3AK, DC＋CD3AK and CEA-rV＋DC＋CD3AK, was measured respectively by MTT reduction assay. Results： （1） 4 target cells were con- firmed by CEA monoclonal antibody of rabbit anti-human. Lovo and A549 were really CEA positive cell lines, while Bel-7402 and K562 were CEA negative cell lines. （2） It was showed by flow-cytometry that the mature DC cultured at 10th day expressed MHC I, II molecules such as CD86, CDS0, CD83 and CD40 highly, but CD123 lowly. The expression rates of CD86, CDS0, CD83 and CD40 was 82.7%, 51.1%, 57.5% and 69.4%, respectively. The appearances and intra-cellular structures of DC were observed through light and electron microscope. The diameter of mature DC was 15-20 μm presented the irregular morphologic appearanca, much prominences and pseudopodium. There were abundant mitochondria and endoplasmic reticulum in DC endochylema. （3） The rates of CD3, CD4, CD8 and CD28 in CD3AK cells group were 2 folds higher than that in UBMC group by FACS. It was said that the numbers of the mature T lymphocyte in CD3AK cells group were much greater than that in UBMC group. （4） The killing activities to 4 target cells of 3 effector＇s cells, which included CEA-rV＋DC＋CD3AK, DC＋CD3AK and CD3AK, were much greater than that of UBMC （P〈0.01）. Moreover, comparing with the killing activities of 4 effector＇s： CEA-rV＋DC＋CD3AK group 〉 DC＋CD3AK group 〉 CD3AK group 〉 UBMC group. It showed that, cytokine, DC and CEA-rV could efficiently elevate the killing activity of UBMC on broad-spectrum tumor cells. （5） Comparing with the killing activities of CEA-rV＋DC＋CD3AK and CD3AK cells to CEA positive and negative cells, the killing activities of CEA-rV＋DC＋CD3AK to CEA positive tumor calls, Lovo and A549 calls （P〈0.01） were remarkably better than that to CEA negative tumor cells BEL-7402 and K562 cells （P〈0.05）. It was said that the CEA-rV＋DC could obviously enhance the killing activity of CD3AK on CEA positive tumor cells. Comparing with the killing activities of CEA-rV＋DC＋CD3AK and DC＋CD3AK cells, the killing activity of CD3AK on CEA negative tumor cells was no statistical difference （P〉0.05）. However, the killing activity to CEA positive cells of CEA-rV＋DC＋CD3AK group was notably higher than that of DC＋CD3AK group. Namely, CEA-rV could distinctly promote the special killing activity to CEA positive tumor cells of CD3AK, but could not do it to CEA negative tumor cells. Conclusion： CEA-rV＋DC could obviously enhance the special killing activity of CD3AK on CEA positive tumor cell lines, while the DC only couldn＇t. The results indicated that the CEA-rV played an important role during the special killing activity of CD3AK cells to CEA positive tumor cells.展开更多
Background: In the previous study, we established an ischemia-prone gerbil population(IG), which was selectively bred to increase the incidence of unilateral carotid arterial occlusion(UCO)-induced ischemia in Mongoli...Background: In the previous study, we established an ischemia-prone gerbil population(IG), which was selectively bred to increase the incidence of unilateral carotid arterial occlusion(UCO)-induced ischemia in Mongolian gerbils. However, if the characteristics of ischemia model in IG are the same as those in general gerbils(GG), and if the neurological symptoms are associated with the neurological insults in IG is still unclear.Methods: In the present study, we evaluated the UCO model in IG by analyzing neurological symptoms, neurological injury in the hippocampal CA1 region and compared with GG.Results: The data showed that the ratios of neurological symptom scores ≥ 2 in the IG and GG groups were 65.0% vs 30.0%, respectively, and were significantly different(P <.01).The neuronal damage following a UCO ischemic insult in the IG group was more severe compared to the GG group. There was a high correlation between the neurological insults' scale and the neurological symptom score in the IG and GG groups(r =.979 and.943 in the IG and GG groups, respectively). In animals with mild neurological symptom scores(2 and 3), the neuronal insults were significantly different between female and male gerbils in both IG and GG.Conclusion: Our findings suggest that IG population would likely be more advantageous to establish an ischemic model.展开更多
Objective：To study the genetic variation of mitochondrial DNA （mtDNA） among common laboratory strains of inbred mice. Methods： The genetic polymorphism of mtDNA among 4 classical laboratory strains of inbred mice ...Objective：To study the genetic variation of mitochondrial DNA （mtDNA） among common laboratory strains of inbred mice. Methods： The genetic polymorphism of mtDNA among 4 classical laboratory strains of inbred mice and 3 inbred strains of mice established in China was analyzed by polymerase chain reaction coupled with restriction fragment length polymorphism（PCR-RFLP） and PCR coupled with single-stranded conformation polymorphism（PCR-SSCP）. Results： With regard to the D-loop （Displacement loop, D-loop）, tRNA^ Met＋Glu＋Ile, and ND3 （NADH dehydrogenase subunit 3, ND3） gene fragments of mtDNA from these mice,no variation was revealed by PCR-RFLP at 46 restriction enzyme sites. Further analyzed by PCR-SSCP,the D-loop 5＇fragment and 3＇end fragment of mtDNA from these mice also showed no genetic variation. Conclusion： Owing to maternal mode of inheritance of mtDNA,the results indicate that these common inbred strains of mice share the same maternal lineage.展开更多
Objective: To observe effects of Dan Wei Powder (胆胃散 Powder for treating the gall bladder and stomach) Tea Bag (DWSTB) on the aggregation rate of blood platelet in vivo and in vitro. Methods: Increase of the platel...Objective: To observe effects of Dan Wei Powder (胆胃散 Powder for treating the gall bladder and stomach) Tea Bag (DWSTB) on the aggregation rate of blood platelet in vivo and in vitro. Methods: Increase of the platelet aggregation rate in the rat in vivo was induced by carrageenin, and increase of the rabbit platelet aggregation rate in vitro was induced by adenosine diphosphate (ADP) and collagen, respectively. The effects of DWSTB on the platelet aggregation rate were investigated in vivo and in vitro, respectively. Results: The maximum in vivo platelet aggregation rate in the rat was significantly decreased after administration of 2.0 and 4.0 g·kg-1 DWSTB (P<0.05.P<0.01). The maximum rabbit platelet aggregation rate induced by ADP and collagen in vitro were suppressed significantly by 2.0-16.0 mg·mL-1 and 2.0-8.0 mg·mL-1 DWSTB, respectively (P<0.05.P<0.01). And the effect of DWSTB on platelet aggregation was raised with increase ofits dose. Conclusion: Dan Wei Powder Tea Bag can restrain the aggregation of platelet in vivo and in vitro.展开更多
The nonlineat third order optical susceptibility of C_(60) films on roughed glass plate has been studied by using a inode locked Nd:YAG laser emitting 8ps pulsed at 1.064 μm of 0.3 J energy.The large|χ^(3)(-3ω,ω,...The nonlineat third order optical susceptibility of C_(60) films on roughed glass plate has been studied by using a inode locked Nd:YAG laser emitting 8ps pulsed at 1.064 μm of 0.3 J energy.The large|χ^(3)(-3ω,ω,ω,ω)|=2 ×10^(-8) esu for C_(60) films of 15μm thickness has been observed,which is 1O^(3) larger than the value in the bulk C_(60).This is due to surface enhanced effect.展开更多
Staphylococcus epidermidis is one of the leading pathogens of nosocomial infections. Twenty- eight strains of biofilm-negative Staphylococcus epidermidis, of which thirteen strains considered as the clinical strains w...Staphylococcus epidermidis is one of the leading pathogens of nosocomial infections. Twenty- eight strains of biofilm-negative Staphylococcus epidermidis, of which thirteen strains considered as the clinical strains were isolated from catheters, blood and urine of patients in Huashan Hospital （Shanghai, China） and fifteen strains considered as commensal strains were isolated from the skin of healthy students who had no contact with hospitals in recent half year, were investigated for the adherence to human umbilical vein endothelial cell line ECV304 and human cervical adenocarcinoma cell line Hela, respectively. Our results showed that the clinical strains were much more adhesive to both cells than commensal ones. The endothelial adherence may be a virulence factor associated with this bacterial pathogenesis.展开更多
Up to now,“Turn-on”fluorescence sensor exhibits promising potential toward the detection of heavy metal ions,anions,drugs,organic dyes,DNA,pesticides,and other amino acids due to their simple,quick detection,and hig...Up to now,“Turn-on”fluorescence sensor exhibits promising potential toward the detection of heavy metal ions,anions,drugs,organic dyes,DNA,pesticides,and other amino acids due to their simple,quick detection,and high sensitivity and selectivity.Herein,a novel fluorescence method of detecting Cr^(3+)in an aqueous solution was described based on the fluorescence resonance energy transfer between rhodamine B(Rh B)and gold nanoparticles(Au NPs).The fluorescence of Rh B solution could be obviously quenched(“off”state)with the presence of citrate-stabilized Au NPs.However,upon addition of Cr^(3+)to Au NPs@Rh B system,the fluorescence of Au NPs was recovered owing to the strong interaction between Cr^(3+)and the specific groups on the surface of citrate-stabilized Au NPs,which will lead to the aggregation of Au NPs(“on”state).At this point,the color of the reaction solution turned to black.Under optimal conditions,the limit of detection(LOD)for Cr^(3+)was 0.95 n M(signal-to-noise ratio,S/N=3)with a linear range of 0.164 n M to 3.270μM.Furthermore,the proposed method exhibits excellent performances,such as rapid analysis,high sensitivity,extraordinary selectivity,easy preparation,switch-on fluorescence response,and non-time consuming.展开更多
Background:Hepatitis E virus(HEV)may induce acute self-limiting illnesses or persistent infections.Chronic hepatitis E frequently occurs in immunocompromised persons,including organ transplant recipients,HIV-positive ...Background:Hepatitis E virus(HEV)may induce acute self-limiting illnesses or persistent infections.Chronic hepatitis E frequently occurs in immunocompromised persons,including organ transplant recipients,HIV-positive patients,and those with hematological malignancies.It poses a risk of liver fibrosis and cirrhosis.Data sources:Relevant articles published till September 2024 were located using Pub Med searches.The further search terms utilized were:“immunocompromised”,“solid organ transplant”,“HIV”,“hematological malignancy”,and“hepatitis E virus”.A manual search of references from pivotal articles extended further publications.The search parameters encompass publications in English.Results:The epidemiology,clinical manifestations,diagnostic measures,and therapeutic modalities of chronic hepatitis E were discussed.Immunocompromised individuals who are infected with HEV are at an increased risk of developing chronic infections,which may progress to liver fibrosis and cirrhosis.Current understanding of HEV is still limited,and there is no medicine that specifically targets hepatitis E.Consequently,the prevention and management of hepatitis E continue to present a significant challenge.Conclusions:Chronic hepatitis E patients need special attention in clinical practice.The relevant risk factors must be identified to facilitate accurate diagnosis and the implementation of more effective preventive measures,thereby enhancing the monitoring,treatment,and prevention of immunocompromised individuals.展开更多
Chronic pancreatitis(CP)is a progressive and irreversible fibroinflammatory disease that markedly increases susceptibility to pancreatic cancer and remains without effective targeted therapies.Among the genetic contri...Chronic pancreatitis(CP)is a progressive and irreversible fibroinflammatory disease that markedly increases susceptibility to pancreatic cancer and remains without effective targeted therapies.Among the genetic contributors to CP,the carboxypeptidase A1 p.Ser282Pro(CPA1^(S282P))variant has been proposed to promote disease through misfolding-induced endoplasmic reticulum stress(ERS),although the broader pathogenic landscape remains incompletely defined.This study generated a rabbit model mimicking the human CPA1S282P mutation using the SpRY-ABE-8.17 system.Homozygous CPA1^(S282P)rabbits exhibited characteristic human CP phenotypes following alcohol induction,including visceral pain,elevated serum lipase and amylase,inflammatory cell infiltration,and extensive pancreatic fibrosis.Biochemical analyses confirmed that the p.S282P mutation induced CPA1 misfolding and elevated the expression of ERS markers GRP78 and CHOP in both transfected HEK293T cells and homozygous mutant rabbits.Notably,the CPA1^(S282P)mutation markedly disrupted intra-pancreatic lipid homeostasis,contributing to the development of CP in mutant rabbits.This study successfully established the first rabbit model of CP that accurately recapitulates CP caused by a defined human point mutation.Additionally,this study provides insights into a previously unrecognized link between CPA1 and intra-pancreatic lipid metabolism,offering a foundation for identifying novel therapeutic targets for human CP.展开更多
Background and objective Heparanase has been thought to be a good molecular marker of tumor,and the heparanase expression level was correlated closely with tumor metastasis. In this study,we investigate the effects of...Background and objective Heparanase has been thought to be a good molecular marker of tumor,and the heparanase expression level was correlated closely with tumor metastasis. In this study,we investigate the effects of heparanase on angiogenesis and lymphangiogenesis of lung cancer and the relationship between heparanase expression and vascular endothelial growth factor (VEGF),vascular endothelial growth factor-C (VEGF-C). Methods Immunohistochemistry was used to detect the expression of heparanase,VEGF,VEGF-C protein and microvascular density (MVD),lymphatic vessel density (LVD) in 115 cases of non-small cell lung cancer (NSCLC) and 45 cases of adjacent normal tissue samples. Results Our results showed that heparanase expression was significantly increased in 91 (79.13%) of the 115 cases and correlated with lymph node metastasis (node positive rate 87.0%; node negative rate 36.8%; P=0.003). Heparanase positive expression cases have significantly higher concentration of microvascular density (MVD) and lymphatic vessel density (LVD) as compared with heparanase negative expression cases (P<0.01,P<0.01,respectively),heparanase expression was significantly correlated with VEGF,VEGF-C expression in NSCLC. Conclusion Heparanase overexpression was associated with angiogenesis and lymphangiogenesis of lung cancer,targeting of heparanase may represent a significant therapeutic potential for lung cancer.展开更多
AIM: To investigate whether enteroviral infection might trigger acute pancreatitis in patients made susceptible due to high alcohol consumption. METHODS: Patients with alcohol-induced acute pan-creatitis were analyzed...AIM: To investigate whether enteroviral infection might trigger acute pancreatitis in patients made susceptible due to high alcohol consumption. METHODS: Patients with alcohol-induced acute pan-creatitis were analyzed for signs of simultaneous or preceding enteroviral infection. We studied the serum samples of 40 patients hospitalized for alcohol-induced acute pancreatitis and 40 controls recruited from an alcohol detoxification center. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect enterovirus RNA and diagnose acute viremia. Immuno-globulin G (IgG), immunoglobulin A (IgA) and immuno-globulin M (IgM) enteroviral antibodies were measured using enzyme immunoassay to detect subacute andprevious infections. The samples were considered posi-tive when the antibody titers were≥15 IU. Further-more, using RT-PCR, we studied pancreatic biopsy sam-ples obtained during surgery from nine patients with chronic pancreatitis, one patient with acute pancreatitis and ten control patients with pancreatic carcinoma for evidence of persisting enteroviral RNA in the pancreatic tissue. RESULTS: No enterovirus RNA indicating acute viremia was detected by RT-PCR in the serum samples of any patient or control. A high incidence of positive antibody titers was observed in both study groups: IgM antibod-ies had positive titers in 5/40 (13%) vs 4/40 (10%), P=0.723; IgG in 15/40 (38%) vs 19/40 (48%), P=0.366; and IgA in 25/40 (63%) vs 33/40 (83%), P=0.045, patients and controls, respectively. Ten (25%) patients had severe pancreatitis and two (5%) required treatment in intensive care. The median length of hos-pitalization was 7 d (range: 3-47 d). The severity of acute pancreatitis or the length of hospitalization was not associated with enteroviral IgM, IgG or IgA anti-bodies. Five pancreatic biopsy samples tested positive with RT-PCR, three (8%) in the control group and two (5%) in the patient group (P=0.64). CONCLUSION: The rate of enteroviral infection is not increased in patients with alcohol-induced acute pan-creatitis when compared to alcoholics with similar high alcohol use.展开更多
Gastrointestinal(GI)cancers are a leading cause of cancer morbidity and mortality worldwide.Despite advances in treatment,cancer relapse remains a significant challenge,necessitating novel therapeutic strategies.In th...Gastrointestinal(GI)cancers are a leading cause of cancer morbidity and mortality worldwide.Despite advances in treatment,cancer relapse remains a significant challenge,necessitating novel therapeutic strategies.In this study,we engineered nanobody-based chimeric antigen receptor(CAR)natural killer(NK)cells targeting cadherin 17(CDH17)for the treatment of GI tumors.In addition,to enhance the efficacy of CAR-NK cells,we also incorporated CV1,a CD47–SIRPαaxis inhibitor,to evaluate the anti-tumor effect of this combination.We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner.CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models.Additionally,the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47–signal regulatory proteinα(SIRPα)axis inhibitor CV1,likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment.Collectively,our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers.The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy.Further investigations are warranted to speed up the clinical translation of these findings.展开更多
Background It remains almost a helpless situation for the recurrent implantation failure and pregnancy loss caused by endometrial injury at present. The purpose of this study was to develop a rabbit model of endometri...Background It remains almost a helpless situation for the recurrent implantation failure and pregnancy loss caused by endometrial injury at present. The purpose of this study was to develop a rabbit model of endometrial mechanical injury that could provide a research platform for this difficult clinical predicament. Methods Three experiments were conducted. Experiment 1： Curettages in both uterus horns and copper wire inserting after curettage （double-injury） in one horn. The histological changes were monitored at 0, 24, 48, 72 hours, as well as in 1 and 2 weeks after operation. Experiment 2： Direct copper wire inserting in one horn and double-injury in other horn. The wires in both horns were removed after 2 weeks.展开更多
The myxovirus resistance gene (Mx1) has a broad spectrum of antiviral activities. It is therefore an interestingcandidate gene to improve disease resistance in farm animals. In this study, we report the use of somatic...The myxovirus resistance gene (Mx1) has a broad spectrum of antiviral activities. It is therefore an interestingcandidate gene to improve disease resistance in farm animals. In this study, we report the use of somatic cellnuclear transfer (SCNT) to produce transgenic pigs over-expressing the Mx1 gene. These transgenic pigs expressapproximately 15–25 times more Mx1 mRNA than non-transgenic pigs, and the protein level of Mx1 was alsomarkedly enhanced. We challenged fibroblast cells isolated from the ear skin of transgenic and control pigs withinfluenza A virus and classical swine fever virus (CFSV). Indirect immunofluorescence assay (IFA) revealed a profounddecrease of influenza A proliferation in Mx1 transgenic cells. Growth kinetics showed an approximately 10-foldreduction of viral copies in the transgenic cells compared to non-transgenic controls. Additionally, we found thatthe Mx1 transgenic cells were more resistant to CSFV infection in comparison to non-transgenic cells. These resultsdemonstrate that the Mx1 transgene can protect against viral infection in cells of transgenic pigs and indicate thatthe Mx1 transgene can be harnessed to develop disease-resistant pigs.展开更多
Background： Measuring total serum calcium is important for the diagnosis of diseases. Currently, results from commercial kits for calcium measurement are variable. Generally, the performance of serum calcium measurem...Background： Measuring total serum calcium is important for the diagnosis of diseases. Currently, results from commercial kits for calcium measurement are variable. Generally, the performance of serum calcium measurements is monitored by external quality assessment （EQA） or proficiency testing schemes. However, the commutability of the EQA samples and calibrators is often unknown, which limits the effectiveness of EQA schemes. The aim of this study was to evaluate the bias of serum calcium measurements and the commutability of processed materials. Methods： Inductively coupled plasma mass spectrometry was applied as a comparative method, and 14 routine methods were chosen as test methods. Forty-eight serum samples from individual patients and 25 processed materials were quantified. A scatter plot was generated from patient samples, and 95% prediction intervals were calculated to evaluate the commutability of the processed materials and measurement bias at three concentration levels was used to determine the accuracy of routine assays. Results： All assays showed high precision （total coefficient of variation [CV] 〈2.26%） and correlation coefficients （r 〉 0.99）. For all assays, the mean bias for the 48 patient samples ranged from 0.13 mmol/L to 0.00 mmol/L （-5.61 0.01%）, and the ranges for the three concentrations were 0.10-0.04 mmoUL （-5.71-2.35%）, -0.14-0.01 mmol/L （-5.80-0.30%）, and -0.19-0.04 mmol/L （-6.24-1.22%）. The EQA samples, calibrators, and animal sera exhibited matrix effects in some assays; human serum pools were commutable in all assays; certificate reference materials were commutable in most assays, and only GBW09152 exhibited a matrix effect in one assay： and aqueous reference materials exhibited matrix effects in most assays. Conclusions： Biases for most assays were within the acceptable range, although the accuracy of some assays needs improvement. Human serum pools prepared from patient samples were commutable, and the other tested materials exhibited a matrix effect.展开更多
文摘AIM:To investigate the value of combined detection of circulating cell-free DNA(cfDNA),a-fetal protein(AFP) and a L-fucosidase(AFU) for diagnosis of hepatocellular carcinoma(HCC).METHODS:Serum samples from 39 HCC patients and 45 normal controls were collected.Branched DNA(bDNA) was used to detect the level of cfDNA,and a receiver operating characteristic curve was employed to evaluate the diagnostic sensitivity,specificity,accuracy,positive predictive value,negative predictive value,positive likelihood ratio,negative likelihood ratio and Youden index,and to assess the diagnostic efficiency and their correlations with the clinicopathological features.AFP and AFU were detected by chemiluminescence and colorimetry,respectively.The significance of combined detection of the three biomarkers was discussed.RESULTS:cfDNA level was increased in 22 of the 39 HCC samples and in 2 of the 45 normal controls.cfDNA level in HCC samples was significantly higher than that in normal controls(P < 0.05).There were significant differences in sex and extra-and intrahepatic metastasis(P < 0.05).There was no significant correlation between cfDNA,AFP and AFU in the detection of HCC.The sensitivity of combined detection of cfDNA with one marker(AFP or AFU) and cfDNA with two markers(AFP and AFU) was 71.8%,87.2% and 89.7% vs 56.4%,53.8% and 66.7% for cfDNA,AFP and AFU used alone,respectively,the difference being statistically significant(P < 0.05).CONCLUSION:Quantitative analysis of cfDNA is sensitive and feasible,and the combined detection of cfDNA with AFP or AFU or both could improve the diagnostic sensitivity for HCC.
基金National Natural Science Foundation of China,No.81802071.
文摘BACKGROUND Biliary diseases are common digestive system disorders which may combine with biliary tract infection such as cholecystitis or cholangitis.Thus,rapid identification of the bacteria and their antibiotic susceptibility profiles are crucial for reducing the mortality of patients with biliary tract infection.AIM To identify bacterial species and antibiotic susceptibility for antibacterial therapy and analyze bile cultivation risk factors for increasing detection rates.METHODS This retrospective study was conducted from July 2008 to July 2017.In total,1339 bile samples which were collected during therapeutic endoscopic retrograde cholangiopan-creatography or percutaneous transhepatic cholangiodrainage or other biliary surgeries or biliary drainage were obtained to characterize pathogen spectra,antibiotic susceptibility,and clinical features.Clinical data including age,sex,comorbidities,clinical symptoms,protopathies,and history of biliary tract diseases and surgeries were collated from hospital medical records.Species identification and initial drug susceptibility were further identified by biochemical characterization using the VITEK 2 Compact test.RESULTS Positive microbiological findings were observed in 738 samples.The most frequently encountered strains were gram-negative bacteria(74.94%),including Escherichia coli(37.78%),Pseudomonas aeruginosa(8.96%),and Klebsiella pneumoniae(10.29%).Bile bacteria were largely sensitive to carbapenems,piperacillin/tazobactam,and gentamicin.Gram-negative strains had low susceptibility to ceftriaxone,quinolones and ampicillin.Almost the same microorganisms were present in patients with malignant and benign diseases.The number of samples with Klebsiella pneumoniae in the bile culture were significantly different between patients with malignant and benign diseases(55 vs 30;P=0.019).Age(P<0.001),fever(P<0.001),history of biliary tract diseases and surgeries(both P<0.001),benign disease(P=0.002),and the comorbidity chronic renal insufficiency(P=0.007)affected the positive rates of the bile samples.CONCLUSION Gram-negative bacteria were the most commonly isolated biliary bacteria.We determined the major factors associated with positive detection rates.Microbiological analysis of bile samples allowed accurate antibiotic treatments.
文摘Live poultry markets（LPMs） are crucial places for human infection of influenza A（H7N9 virus）.In Yangtze River Delta,LPMs were closed after the outbreak of human infection with avian influenza A（H7N9） virus,and then reopened when no case was found.Our purpose was to quantify the effect of LPMs＇ operations in this region on the transmission of influenza A（H7N9） virus.We obtained information about dates of symptom onset and locations for all human influenza A（H7N9） cases reported from Shanghai,Jiangsu and Zhejiang provinces by May 31,2014,and acquired dates of closures and reopening of LPMs from official media.A two-phase Bayesian model was fitted by Markov Chain Monte Carlo methods to process the spatial and temporal influence of human cases.A total of 235 cases of influenza A（H7N9） were confirmed in Shanghai,Jiangsu and Zhejiang by May 31,2014.Using these data,our analysis showed that,after LPM closures,the influenza A（H7N9） outbreak disappeared within two weeks in Shanghai,one week in Jiangsu,and one week in Zhejiang,respectively.Local authorities reopened LPMs when there was no outbreak of influenza A（H7N9）,which did not lead to reemergence of human influenza A（H7N9）.LPM closures were effective in controlling the H7N9 outbreak.Reopening of LPM in summer did not increase the risk of human infection with H7N9.Our findings showed that LPMs should be closed immediately in areas where the H7N9 virus is confirmed in LPM.When there is no outbreak of H7N9 virus,LPMs can be reopened to satisfy the Chinese traditional culture of buying live poultry.In the long term,local authorities should take a cautious attitude in permanent LPM closure.
基金Supported by the Social Development Guide Projects of Science and Technology Committee of Jiangsu Province in 2005 (BS2005629)"The Six Major Expert Peaks" Projects of Jiangsu Provincial Government in 2006 [Surentong (2006) 174]
文摘Objective： To investigate the effects of sleep electroencephalogram-modulated repetitive transcranial magnetic stimulation （SEM-rTMS） and conventional rTMS （C-rTMS） on the activity of hypothalamic-pituitary-adrenal （HPA） axis in patients with depression. Methods： In a double-blind, randomized controlled trial, 164 patients diagnosed with depression were randomized to treatment with SEM-rTMS （n=57）, C-rTMS （n=55） or sham rTMS （n=52） for 30 rain every day for 10 d. Before and after treatment plasma concentrations of adrenocorticotropic hormone （ACTH） and cortisol （CORT） were measured, and the 24-item Hamilton Depression Rating Scale （HAMD-24） was used for assessment. Results： The HAMD-24 scores and plasma ACTH and CORT concentrations of these depressive patients before treatment were significantly different from those of the normal control group （P〈0.05）. The HAMD-24 scores and plasma ACTH and CORT concentrations in the SEM-rTMS group and conventional rTMS group were decreased significantly （P〈0.05）. There was a significant positive correlation between the HAMD-24 scores and plasma ACTH （n=240, r=0.105, P=0.048） and CORT concentrations （n-240, r=0.126, P=0.023） in the patients with depression before and after treatment. Conclusion： The antidepressant effect of rTMS, including SEM-rTMS, may be related to its decreasing HPA axis activity. （This trail was registered. No： ChiCTR-TRC-00000465）
基金Project supported by the National Natural Science Foundation of China and China Academy of Engineering Physics （Grant Nos 10376021, 10274055）.
文摘By using the density functional theory （B3LYP） and four highly accurate complete basis set （CBS-Q, CBS-QB3, CBS-Lq, and CBS-4M）ab initio methods, the X（C, N, O）-NO2 bond dissociation energies （BDEs） for CH3NO2, C2H3NO2, C2H5NO2, HONO2, CH3ONO2, C2H5ONO2, NH2NO2 （CH3）2NNO2 are computed. By comparing the computed BDEs and experimental results, it is found that the B3LYP method is unable to predict satisfactorily the results of bond dissociation energy （BDE）; however, all four CBS models are generally able to give reliable predication of the X（C, N, O）-NO2 BDEs for these nitro compounds. Moreover, the CBS-4M calculation is the least computationally demanding among the four CBS methods considered, Therefore, we recommend CBS-4M method as a reliable method of computing the BDEs for this nitro compound system.
基金Supported by a grant from Science & Technique Department of Guang-dong Province of China (No. 2002C30305).
文摘Objective： To survey the special killing activity of CD3AK on anti-CEA-positive tumor enhanced by umbilical cord blood dendritic cell （DC） loaded with CEA recombinant vaccinia virus （CEA-rV）. Methods： Freshly isolated umbilical blood mononuclear calls （UBMC） were cultivated for 3 h. Suspension cells and attached calls were used to induce CD3AK calls and DC separately. DC was loaded with CEA-rV on the 3rd day to prepare CEA-rV＋DC. CD3AK cells were co-cultured with CEA- rV＋DC on the 8th day, to prepare CEA-rV＋DC＋CD3AK. The killing activity of each effector＇s cell, which included UBMC, CD3AK, DC＋CD3AK and CEA-rV＋DC＋CD3AK, was measured respectively by MTT reduction assay. Results： （1） 4 target cells were con- firmed by CEA monoclonal antibody of rabbit anti-human. Lovo and A549 were really CEA positive cell lines, while Bel-7402 and K562 were CEA negative cell lines. （2） It was showed by flow-cytometry that the mature DC cultured at 10th day expressed MHC I, II molecules such as CD86, CDS0, CD83 and CD40 highly, but CD123 lowly. The expression rates of CD86, CDS0, CD83 and CD40 was 82.7%, 51.1%, 57.5% and 69.4%, respectively. The appearances and intra-cellular structures of DC were observed through light and electron microscope. The diameter of mature DC was 15-20 μm presented the irregular morphologic appearanca, much prominences and pseudopodium. There were abundant mitochondria and endoplasmic reticulum in DC endochylema. （3） The rates of CD3, CD4, CD8 and CD28 in CD3AK cells group were 2 folds higher than that in UBMC group by FACS. It was said that the numbers of the mature T lymphocyte in CD3AK cells group were much greater than that in UBMC group. （4） The killing activities to 4 target cells of 3 effector＇s cells, which included CEA-rV＋DC＋CD3AK, DC＋CD3AK and CD3AK, were much greater than that of UBMC （P〈0.01）. Moreover, comparing with the killing activities of 4 effector＇s： CEA-rV＋DC＋CD3AK group 〉 DC＋CD3AK group 〉 CD3AK group 〉 UBMC group. It showed that, cytokine, DC and CEA-rV could efficiently elevate the killing activity of UBMC on broad-spectrum tumor cells. （5） Comparing with the killing activities of CEA-rV＋DC＋CD3AK and CD3AK cells to CEA positive and negative cells, the killing activities of CEA-rV＋DC＋CD3AK to CEA positive tumor calls, Lovo and A549 calls （P〈0.01） were remarkably better than that to CEA negative tumor cells BEL-7402 and K562 cells （P〈0.05）. It was said that the CEA-rV＋DC could obviously enhance the killing activity of CD3AK on CEA positive tumor cells. Comparing with the killing activities of CEA-rV＋DC＋CD3AK and DC＋CD3AK cells, the killing activity of CD3AK on CEA negative tumor cells was no statistical difference （P〉0.05）. However, the killing activity to CEA positive cells of CEA-rV＋DC＋CD3AK group was notably higher than that of DC＋CD3AK group. Namely, CEA-rV could distinctly promote the special killing activity to CEA positive tumor cells of CD3AK, but could not do it to CEA negative tumor cells. Conclusion： CEA-rV＋DC could obviously enhance the special killing activity of CD3AK on CEA positive tumor cell lines, while the DC only couldn＇t. The results indicated that the CEA-rV played an important role during the special killing activity of CD3AK cells to CEA positive tumor cells.
基金Key Projects in the National Science&Technology Pillar Program,Grant/Award Number:2015BAI09B01
文摘Background: In the previous study, we established an ischemia-prone gerbil population(IG), which was selectively bred to increase the incidence of unilateral carotid arterial occlusion(UCO)-induced ischemia in Mongolian gerbils. However, if the characteristics of ischemia model in IG are the same as those in general gerbils(GG), and if the neurological symptoms are associated with the neurological insults in IG is still unclear.Methods: In the present study, we evaluated the UCO model in IG by analyzing neurological symptoms, neurological injury in the hippocampal CA1 region and compared with GG.Results: The data showed that the ratios of neurological symptom scores ≥ 2 in the IG and GG groups were 65.0% vs 30.0%, respectively, and were significantly different(P <.01).The neuronal damage following a UCO ischemic insult in the IG group was more severe compared to the GG group. There was a high correlation between the neurological insults' scale and the neurological symptom score in the IG and GG groups(r =.979 and.943 in the IG and GG groups, respectively). In animals with mild neurological symptom scores(2 and 3), the neuronal insults were significantly different between female and male gerbils in both IG and GG.Conclusion: Our findings suggest that IG population would likely be more advantageous to establish an ischemic model.
基金Supported by Developmental Programming Item of National Keystone Basic Research (G2000016106) and National Natural Science Foundation of China (No. 39600079)
文摘Objective：To study the genetic variation of mitochondrial DNA （mtDNA） among common laboratory strains of inbred mice. Methods： The genetic polymorphism of mtDNA among 4 classical laboratory strains of inbred mice and 3 inbred strains of mice established in China was analyzed by polymerase chain reaction coupled with restriction fragment length polymorphism（PCR-RFLP） and PCR coupled with single-stranded conformation polymorphism（PCR-SSCP）. Results： With regard to the D-loop （Displacement loop, D-loop）, tRNA^ Met＋Glu＋Ile, and ND3 （NADH dehydrogenase subunit 3, ND3） gene fragments of mtDNA from these mice,no variation was revealed by PCR-RFLP at 46 restriction enzyme sites. Further analyzed by PCR-SSCP,the D-loop 5＇fragment and 3＇end fragment of mtDNA from these mice also showed no genetic variation. Conclusion： Owing to maternal mode of inheritance of mtDNA,the results indicate that these common inbred strains of mice share the same maternal lineage.
文摘Objective: To observe effects of Dan Wei Powder (胆胃散 Powder for treating the gall bladder and stomach) Tea Bag (DWSTB) on the aggregation rate of blood platelet in vivo and in vitro. Methods: Increase of the platelet aggregation rate in the rat in vivo was induced by carrageenin, and increase of the rabbit platelet aggregation rate in vitro was induced by adenosine diphosphate (ADP) and collagen, respectively. The effects of DWSTB on the platelet aggregation rate were investigated in vivo and in vitro, respectively. Results: The maximum in vivo platelet aggregation rate in the rat was significantly decreased after administration of 2.0 and 4.0 g·kg-1 DWSTB (P<0.05.P<0.01). The maximum rabbit platelet aggregation rate induced by ADP and collagen in vitro were suppressed significantly by 2.0-16.0 mg·mL-1 and 2.0-8.0 mg·mL-1 DWSTB, respectively (P<0.05.P<0.01). And the effect of DWSTB on platelet aggregation was raised with increase ofits dose. Conclusion: Dan Wei Powder Tea Bag can restrain the aggregation of platelet in vivo and in vitro.
基金Supported by the National Natuiil Science Foundation of China,S.F.of Zhejiang Province,P.R.C.and Doctoral Foundation of China.
文摘The nonlineat third order optical susceptibility of C_(60) films on roughed glass plate has been studied by using a inode locked Nd:YAG laser emitting 8ps pulsed at 1.064 μm of 0.3 J energy.The large|χ^(3)(-3ω,ω,ω,ω)|=2 ×10^(-8) esu for C_(60) films of 15μm thickness has been observed,which is 1O^(3) larger than the value in the bulk C_(60).This is due to surface enhanced effect.
基金This work was supported by the Chinese National Natural Science Foundation(30670108)Shanghai Municipal Science and Technology Commission(05PJ14025).
文摘Staphylococcus epidermidis is one of the leading pathogens of nosocomial infections. Twenty- eight strains of biofilm-negative Staphylococcus epidermidis, of which thirteen strains considered as the clinical strains were isolated from catheters, blood and urine of patients in Huashan Hospital （Shanghai, China） and fifteen strains considered as commensal strains were isolated from the skin of healthy students who had no contact with hospitals in recent half year, were investigated for the adherence to human umbilical vein endothelial cell line ECV304 and human cervical adenocarcinoma cell line Hela, respectively. Our results showed that the clinical strains were much more adhesive to both cells than commensal ones. The endothelial adherence may be a virulence factor associated with this bacterial pathogenesis.
基金supported by the Natural Science Foundation of Qinghai Province in China(No.2019-ZJ-944Q)the University-level Planning Project of Qinghai Minzu University of Qinghai Province in China(Nos.2022GH11 and 2022GH13)。
文摘Up to now,“Turn-on”fluorescence sensor exhibits promising potential toward the detection of heavy metal ions,anions,drugs,organic dyes,DNA,pesticides,and other amino acids due to their simple,quick detection,and high sensitivity and selectivity.Herein,a novel fluorescence method of detecting Cr^(3+)in an aqueous solution was described based on the fluorescence resonance energy transfer between rhodamine B(Rh B)and gold nanoparticles(Au NPs).The fluorescence of Rh B solution could be obviously quenched(“off”state)with the presence of citrate-stabilized Au NPs.However,upon addition of Cr^(3+)to Au NPs@Rh B system,the fluorescence of Au NPs was recovered owing to the strong interaction between Cr^(3+)and the specific groups on the surface of citrate-stabilized Au NPs,which will lead to the aggregation of Au NPs(“on”state).At this point,the color of the reaction solution turned to black.Under optimal conditions,the limit of detection(LOD)for Cr^(3+)was 0.95 n M(signal-to-noise ratio,S/N=3)with a linear range of 0.164 n M to 3.270μM.Furthermore,the proposed method exhibits excellent performances,such as rapid analysis,high sensitivity,extraordinary selectivity,easy preparation,switch-on fluorescence response,and non-time consuming.
基金supported by grants from the National Natural Science Foundation of China(82272396)Gusu Health Project of Suzhou(GSWS2022076 and GSWS2023004)。
文摘Background:Hepatitis E virus(HEV)may induce acute self-limiting illnesses or persistent infections.Chronic hepatitis E frequently occurs in immunocompromised persons,including organ transplant recipients,HIV-positive patients,and those with hematological malignancies.It poses a risk of liver fibrosis and cirrhosis.Data sources:Relevant articles published till September 2024 were located using Pub Med searches.The further search terms utilized were:“immunocompromised”,“solid organ transplant”,“HIV”,“hematological malignancy”,and“hepatitis E virus”.A manual search of references from pivotal articles extended further publications.The search parameters encompass publications in English.Results:The epidemiology,clinical manifestations,diagnostic measures,and therapeutic modalities of chronic hepatitis E were discussed.Immunocompromised individuals who are infected with HEV are at an increased risk of developing chronic infections,which may progress to liver fibrosis and cirrhosis.Current understanding of HEV is still limited,and there is no medicine that specifically targets hepatitis E.Consequently,the prevention and management of hepatitis E continue to present a significant challenge.Conclusions:Chronic hepatitis E patients need special attention in clinical practice.The relevant risk factors must be identified to facilitate accurate diagnosis and the implementation of more effective preventive measures,thereby enhancing the monitoring,treatment,and prevention of immunocompromised individuals.
基金supported by the Jilin Provincial Department of Education Science and Technology Research Project(JJKH20231141K)Natural Science Foundation of Jilin Province of China(20230101154JC)Young Elite Scientists Sponsorship Program by CAST(2022QNRC001)。
文摘Chronic pancreatitis(CP)is a progressive and irreversible fibroinflammatory disease that markedly increases susceptibility to pancreatic cancer and remains without effective targeted therapies.Among the genetic contributors to CP,the carboxypeptidase A1 p.Ser282Pro(CPA1^(S282P))variant has been proposed to promote disease through misfolding-induced endoplasmic reticulum stress(ERS),although the broader pathogenic landscape remains incompletely defined.This study generated a rabbit model mimicking the human CPA1S282P mutation using the SpRY-ABE-8.17 system.Homozygous CPA1^(S282P)rabbits exhibited characteristic human CP phenotypes following alcohol induction,including visceral pain,elevated serum lipase and amylase,inflammatory cell infiltration,and extensive pancreatic fibrosis.Biochemical analyses confirmed that the p.S282P mutation induced CPA1 misfolding and elevated the expression of ERS markers GRP78 and CHOP in both transfected HEK293T cells and homozygous mutant rabbits.Notably,the CPA1^(S282P)mutation markedly disrupted intra-pancreatic lipid homeostasis,contributing to the development of CP in mutant rabbits.This study successfully established the first rabbit model of CP that accurately recapitulates CP caused by a defined human point mutation.Additionally,this study provides insights into a previously unrecognized link between CPA1 and intra-pancreatic lipid metabolism,offering a foundation for identifying novel therapeutic targets for human CP.
文摘Background and objective Heparanase has been thought to be a good molecular marker of tumor,and the heparanase expression level was correlated closely with tumor metastasis. In this study,we investigate the effects of heparanase on angiogenesis and lymphangiogenesis of lung cancer and the relationship between heparanase expression and vascular endothelial growth factor (VEGF),vascular endothelial growth factor-C (VEGF-C). Methods Immunohistochemistry was used to detect the expression of heparanase,VEGF,VEGF-C protein and microvascular density (MVD),lymphatic vessel density (LVD) in 115 cases of non-small cell lung cancer (NSCLC) and 45 cases of adjacent normal tissue samples. Results Our results showed that heparanase expression was significantly increased in 91 (79.13%) of the 115 cases and correlated with lymph node metastasis (node positive rate 87.0%; node negative rate 36.8%; P=0.003). Heparanase positive expression cases have significantly higher concentration of microvascular density (MVD) and lymphatic vessel density (LVD) as compared with heparanase negative expression cases (P<0.01,P<0.01,respectively),heparanase expression was significantly correlated with VEGF,VEGF-C expression in NSCLC. Conclusion Heparanase overexpression was associated with angiogenesis and lymphangiogenesis of lung cancer,targeting of heparanase may represent a significant therapeutic potential for lung cancer.
文摘AIM: To investigate whether enteroviral infection might trigger acute pancreatitis in patients made susceptible due to high alcohol consumption. METHODS: Patients with alcohol-induced acute pan-creatitis were analyzed for signs of simultaneous or preceding enteroviral infection. We studied the serum samples of 40 patients hospitalized for alcohol-induced acute pancreatitis and 40 controls recruited from an alcohol detoxification center. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect enterovirus RNA and diagnose acute viremia. Immuno-globulin G (IgG), immunoglobulin A (IgA) and immuno-globulin M (IgM) enteroviral antibodies were measured using enzyme immunoassay to detect subacute andprevious infections. The samples were considered posi-tive when the antibody titers were≥15 IU. Further-more, using RT-PCR, we studied pancreatic biopsy sam-ples obtained during surgery from nine patients with chronic pancreatitis, one patient with acute pancreatitis and ten control patients with pancreatic carcinoma for evidence of persisting enteroviral RNA in the pancreatic tissue. RESULTS: No enterovirus RNA indicating acute viremia was detected by RT-PCR in the serum samples of any patient or control. A high incidence of positive antibody titers was observed in both study groups: IgM antibod-ies had positive titers in 5/40 (13%) vs 4/40 (10%), P=0.723; IgG in 15/40 (38%) vs 19/40 (48%), P=0.366; and IgA in 25/40 (63%) vs 33/40 (83%), P=0.045, patients and controls, respectively. Ten (25%) patients had severe pancreatitis and two (5%) required treatment in intensive care. The median length of hos-pitalization was 7 d (range: 3-47 d). The severity of acute pancreatitis or the length of hospitalization was not associated with enteroviral IgM, IgG or IgA anti-bodies. Five pancreatic biopsy samples tested positive with RT-PCR, three (8%) in the control group and two (5%) in the patient group (P=0.64). CONCLUSION: The rate of enteroviral infection is not increased in patients with alcohol-induced acute pan-creatitis when compared to alcoholics with similar high alcohol use.
基金funded by the National Key Research and Development Program of China(2022YFC2303600)the Key Special Project of“Strategic Science and Technology Innovation Cooperation”from National Key R&D Program(2023YFE0204500,China)+11 种基金Shenzhen Science and Technology Innovation Committee(RCBS20210706092213007,China)the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(CI2023D003,CI2021B014,and CI2023D008,China)the CACMS Innovation Fund(CI2023E002,CI2021A05101,and CI2021A05104,China)the Science and Technology Foundation of Shenzhen(JCYJ20210324115800001,JCYJ20210324113608023,and JCYJ20200109120205924,China)the Science and Technology Foundation of Shenzhen(Shenzhen Clinical Medical Research Center for Geriatric Diseases)the Shenzhen Medical Research Fund(B2302051,China)the Shenzhen Science and Technology Innovation Committee(SZSTI)(RCYX20221008092950121,China)the National Natural Science Foundation of China(82373775,32101219,82103140,and 82304518)the Natural Science Foundation of Top Talent of SZTU(GDRC202125,China)the HUILAN Public Welfare,the Shenzhen Science and Technology Innovation Commission(JCYJ20200109120205924,China)Shenzhen Key Medical Discipline Construction Fund(SZXK046,China)Guangdong Basic and Applied Basic Research Foundation(2021A1515012164,2022A1515110745,and 2021A1515111188,China)International Science and Technology Cooperation for Shenzhen Technology Innovation Plan(GJHZ20200731095411034,China).
文摘Gastrointestinal(GI)cancers are a leading cause of cancer morbidity and mortality worldwide.Despite advances in treatment,cancer relapse remains a significant challenge,necessitating novel therapeutic strategies.In this study,we engineered nanobody-based chimeric antigen receptor(CAR)natural killer(NK)cells targeting cadherin 17(CDH17)for the treatment of GI tumors.In addition,to enhance the efficacy of CAR-NK cells,we also incorporated CV1,a CD47–SIRPαaxis inhibitor,to evaluate the anti-tumor effect of this combination.We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner.CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models.Additionally,the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47–signal regulatory proteinα(SIRPα)axis inhibitor CV1,likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment.Collectively,our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers.The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy.Further investigations are warranted to speed up the clinical translation of these findings.
文摘Background It remains almost a helpless situation for the recurrent implantation failure and pregnancy loss caused by endometrial injury at present. The purpose of this study was to develop a rabbit model of endometrial mechanical injury that could provide a research platform for this difficult clinical predicament. Methods Three experiments were conducted. Experiment 1： Curettages in both uterus horns and copper wire inserting after curettage （double-injury） in one horn. The histological changes were monitored at 0, 24, 48, 72 hours, as well as in 1 and 2 weeks after operation. Experiment 2： Direct copper wire inserting in one horn and double-injury in other horn. The wires in both horns were removed after 2 weeks.
基金This work was supported by grants from National Basic Research Program of China(973 program)(2011CB944203)ZNGI-2011-010 from the Guangzhou Municipality and the Chinese Academy and Sciences to L.L.
文摘The myxovirus resistance gene (Mx1) has a broad spectrum of antiviral activities. It is therefore an interestingcandidate gene to improve disease resistance in farm animals. In this study, we report the use of somatic cellnuclear transfer (SCNT) to produce transgenic pigs over-expressing the Mx1 gene. These transgenic pigs expressapproximately 15–25 times more Mx1 mRNA than non-transgenic pigs, and the protein level of Mx1 was alsomarkedly enhanced. We challenged fibroblast cells isolated from the ear skin of transgenic and control pigs withinfluenza A virus and classical swine fever virus (CFSV). Indirect immunofluorescence assay (IFA) revealed a profounddecrease of influenza A proliferation in Mx1 transgenic cells. Growth kinetics showed an approximately 10-foldreduction of viral copies in the transgenic cells compared to non-transgenic controls. Additionally, we found thatthe Mx1 transgenic cells were more resistant to CSFV infection in comparison to non-transgenic cells. These resultsdemonstrate that the Mx1 transgene can protect against viral infection in cells of transgenic pigs and indicate thatthe Mx1 transgene can be harnessed to develop disease-resistant pigs.
文摘Background： Measuring total serum calcium is important for the diagnosis of diseases. Currently, results from commercial kits for calcium measurement are variable. Generally, the performance of serum calcium measurements is monitored by external quality assessment （EQA） or proficiency testing schemes. However, the commutability of the EQA samples and calibrators is often unknown, which limits the effectiveness of EQA schemes. The aim of this study was to evaluate the bias of serum calcium measurements and the commutability of processed materials. Methods： Inductively coupled plasma mass spectrometry was applied as a comparative method, and 14 routine methods were chosen as test methods. Forty-eight serum samples from individual patients and 25 processed materials were quantified. A scatter plot was generated from patient samples, and 95% prediction intervals were calculated to evaluate the commutability of the processed materials and measurement bias at three concentration levels was used to determine the accuracy of routine assays. Results： All assays showed high precision （total coefficient of variation [CV] 〈2.26%） and correlation coefficients （r 〉 0.99）. For all assays, the mean bias for the 48 patient samples ranged from 0.13 mmol/L to 0.00 mmol/L （-5.61 0.01%）, and the ranges for the three concentrations were 0.10-0.04 mmoUL （-5.71-2.35%）, -0.14-0.01 mmol/L （-5.80-0.30%）, and -0.19-0.04 mmol/L （-6.24-1.22%）. The EQA samples, calibrators, and animal sera exhibited matrix effects in some assays; human serum pools were commutable in all assays; certificate reference materials were commutable in most assays, and only GBW09152 exhibited a matrix effect in one assay： and aqueous reference materials exhibited matrix effects in most assays. Conclusions： Biases for most assays were within the acceptable range, although the accuracy of some assays needs improvement. Human serum pools prepared from patient samples were commutable, and the other tested materials exhibited a matrix effect.
