AIM: To investigate the changes in clinical symptoms and gastric emptying and their association in functional dyspepsia(FD) patients.METHODS: Seventy FD patients were enrolled and divided into 2 groups Helicobacter py...AIM: To investigate the changes in clinical symptoms and gastric emptying and their association in functional dyspepsia(FD) patients.METHODS: Seventy FD patients were enrolled and divided into 2 groups Helicobacter pylori(H. pylori)-negative group(28 patients), and H. pylori-positive group(42 patients). Patients in the H. pylori-positive group were further randomly divided into groups: H. pylori-treatment group(21 patients) and conventional treatment group(21 patients). Seventy two healthy subjects were selected as the control group. The proximal and distal stomach area was measured by ultrasound immediately after patients took the test meal, and at 20, 40, 60 and 90 min; then, gastric half-emptying time was calculated. The incidence of symptoms and gastric half-emptying time between the FD and control groups were compared. The H. pylori-negative and conventional treatment groups were givenconventional treatment: domperidone 0.6 mg/(kg/d) for 1 mo. The H. pylori-treatment group was given H. pylori eradication treatment + conventional treatment: lansoprazole 30 mg once daily, clarithromycin 0.5 g twice daily and amoxicillin 1.0 g twice daily for 1 wk, then domperidone 0.6 mg/(kg/d) for 1 mo. The incidence of symptoms and gastric emptying were compared between the FD and control groups. The relationship between dyspeptic symptoms and gastric half-emptying time in the FD and control groups were analyzed. Then total symptom scores before and after treatment and gastric half-emptying time were compared among the 3 groups. RESULTS: The incidence of abdominal pain, epigastric burning sensation, abdominal distension, nausea, belching, and early satiety symptoms in the FD group were significantly higher than in the control group(50.0% vs 20.8%; 37.1% vs 12.5%; 78.6% vs 44.4%; 45.7% vs 22.2%; 52.9% vs 15.3%; 57.1% vs 19.4%; all P < 0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the FD group were slower than in the control group(93.7 ± 26.2 vs 72.0 ± 14.3; 102.2 ± 26.4 vs 87.5 ± 18.2; 102.1 ± 28.6 vs 78.3 ± 14.1; all P < 0.05). Abdominal distension, belching and early satiety had an effect on distal gastric half-emptying time(P < 0.05). Abdominal distension and abdominal pain had an effect on the gastric half-emptying time of the whole stomach(P < 0.05). All were risk factors(odds ratio > 1). The total symptom score of the 3 groups after treatment was lower than before treatment(P < 0.05). Total symptom scores after treatment in the H. pylori-treatment group and H. pylori-negative group were lower than in the conventional treatment group(5.15 ± 2.27 vs 7.02 ± 3.04, 4.93 ± 3.22 vs 7.02 ± 3.04, All P < 0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the H. pylori-negative and H. pylori-treatment groups were shorter than in the conventional treatment group(P < 0.05). CONCLUSION: FD patients have delayed gastric emptying. H. pylori infection treatment helps to improve symptoms of dyspepsia and is a reasonable choice for treatment in clinical practice.展开更多
BACKGROUND Autism is the most common clinical developmental disorder in children.The childhood autism rating scale(CARS)and autistic autism behavior checklist(ABC)are the most commonly used assessment scales for diagn...BACKGROUND Autism is the most common clinical developmental disorder in children.The childhood autism rating scale(CARS)and autistic autism behavior checklist(ABC)are the most commonly used assessment scales for diagnosing autism.However,the diagnostic validations and the corresponding cutoffs for CARS and ABC in individuals with suspected autism spectrum disorder(ASD)remain unclear.Furthermore,for suspected ASD in China,it remains unclear whether CARS is a better diagnostic tool than ABC.Also unclear is whether the current cutoff points for ABC and CARS are suitable for the accurate diagnosis of ASD.AIM To investigate the diagnostic validity of CARS and ABC based on a large Chinese sample.METHODS A total of 591 outpatient children from the ASD Unit at Beijing Children’s Hospital between June and November 2019 were identified.First,the Clancy autism behavior scale(CABS)was used to screen out suspected autism from these children.Then,each suspected ASD was evaluated by CARS and ABC.Receiver operating characteristic(ROC)curve analysis was used to compare diagnostic validations.We also calculated the area under the curve(AUC)for both CARS and ABC.RESULTS We found that the Cronbach alpha coefficients of CARS and ABC were 0.772 and 0.426,respectively.Therefore,the reliability of the CARS was higher than that of the ABC.In addition,we found that the correlation between CARS and CABS was 0.732.Next,we performed ROC curve analysis for CARS and ABC,which yielded AUC values of 0.846 and 0.768,respectively.The cutoff value,which is associated with the maximum Youden index,is usually applied as a decision threshold.We found that the cutoff values of CARS and ABC were 34 and 67,respectively.CONCLUSION This result indicated that CARS is superior to ABC in the Chinese population with suspected ASD.展开更多
Intrahepatic cholangiocarcinoma(ICC)is a relatively rare form of liver cancer with a poor prognosis.The therapeutic options for patients with advanced ICC are limited and usually ineffective.There is currently no appr...Intrahepatic cholangiocarcinoma(ICC)is a relatively rare form of liver cancer with a poor prognosis.The therapeutic options for patients with advanced ICC are limited and usually ineffective.There is currently no approved targeted therapy for ICC,although accumulating evidence supports inhibition of the PI3K/Akt/m TOR signaling pathway as a promising therapeutic strategy in the treatment of ICC.Here,we report a patient with stage IV ICC harboring a PIK3 CA mutation who responded well to the m TOR inhibitor everolimus.Computed tomography and magnetic resonance imaging demonstrated shrinkage of the tumor and maintenance of a partial response for 6.5 mo after everolimus treatment as the best response.To the best of our knowledge,this is the first clinical case report in the literature of clinical benefit from everolimus treatment in an ICC patient with PIK3 CA mutation.展开更多
Acute kidney injury(AKI)is a clinical syndrome characterized by a rapid deterioration in kidney function and has a significant impact on patient health and survival.Mesenchymal stem cells(MSCs)have the potential to en...Acute kidney injury(AKI)is a clinical syndrome characterized by a rapid deterioration in kidney function and has a significant impact on patient health and survival.Mesenchymal stem cells(MSCs)have the potential to enhance renal function by suppressing the expression of cell cycle inhibitors and reducing the expression of senescence markers and microRNAs via paracrine and endocrine mechanisms.MSC-derived exosomes can alleviate AKI symptoms by regulating DNA damage,apoptosis,and other related signaling pathways through the delivery of proteins,microRNAs,long-chain noncoding RNAs,and circular RNAs.This technique is both safe and effective.MSC-derived exosomes may have great application prospects in the treatment of AKI.Understanding the underlying mechanisms will foster the development of new and promising therapeutic strategies against AKI.This review focused on recent advancements in the role of MSCs in AKI repair as well as the mechanisms underlying the role of MSCs and their secreted exosomes.It is anticipated that novel and profound insights into the functionality of MSCs and their derived exosomes will emerge.展开更多
AIM: To investigate whether bone marrow-derived denritic cells pulsed with tumor lysates induce immunity against gastric cancer ex vivo. METHODS: c-kit+ hematopoietic progenitor cells were magnetically isolated wit...AIM: To investigate whether bone marrow-derived denritic cells pulsed with tumor lysates induce immunity against gastric cancer ex vivo. METHODS: c-kit+ hematopoietic progenitor cells were magnetically isolated with a MiniMACS separator from BALB/c mice bone marrow cells. These cells were cultured with cytokines GM-CSF, IL-4, and TNFα to induce their maturation. They were analysed by morphological observation, phenotype analysis, and mixed lymphocyte reaction (MLR). Bone marrowderived DCs (BM-DCs) were pulsed with tumor cell lysate obtained by rapid freezing and thawing at a 1:3 DC:tumor cell ratio. Finally, cytotoxic T lymphocyte (CTL) activity and interferon gamma (IFNγ) secretion was evaluated ex vivo. RESULTS: c-kit^+ hematopoietic progenitor cells from mice bone marrow cells cultured with cytokines for 8 d showed the character of typical mature DCs.Morphologically, observed by light microscope, these cells were large with oval or irregularly shaped nuclei and with many small dendrites. Phenotypically, FACS analysis showed that they expressed.high levels of la, DEC-205, CD11b, CD80 and CD86 antigen, moderate levels of CD40, and negative for F4/80. Functionally, these cells gained the capacity to stimulate allogeneic T cells in MLR assay. However, immature DCs cultured with cytokines for 5 d did not have typical DCs phenotypic markers and could not stimulate allogeneic T cells. Ex vivo primed T cells with SGC-7901 tumor cell lysate-pulsed (TP) DCs were able to induce effective CTL activity against SGC-7901 tumor cells (E:T = 100:1, 69.55% ± 6.05% specific lysis), but not B16 tumor cells, and produced higher levels of IFNγ, when stimulated with SGC-7901 tumor cells but not when stimulated with B16 tumor cells (1575.31 ± 60.25 pg/mL in SGC-7901 group vs 164.11± 18.52 pg/mL in B16 group, P 〈 0.01). CONCLUSION: BM-derived DCs pulsed with tumor lysates Can induce anti-tumor immunity specific to gastric cancer ex vivo.展开更多
AIM To investigate the antioxidant and hepatoprotective effects of Cortex Dictamni aqueous extract(CDAE) in carbon tetrachloride(CCl4)-induced liver damage in rats.METHODS The in vitro antioxidant effect of CDAE was i...AIM To investigate the antioxidant and hepatoprotective effects of Cortex Dictamni aqueous extract(CDAE) in carbon tetrachloride(CCl4)-induced liver damage in rats.METHODS The in vitro antioxidant effect of CDAE was investigated using α,α-diphenyl-β-picrylhydrazyl(DPPH), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)(ABTS), β-carotene bleaching, reducing power, and thiobarbituric acid reactive substance assays. A linoleic acid system, including ferric thiocyanate(FTC) and thiobarbituric acid(TBA) assays, was used to evaluate the inhibition of lipid peroxidation. The in vivo hepatoprotective and antioxidant effects of CDAEagainst CCl4-induced liver damage were evaluated in Sprague-Dawley rats. Silymarin was used as a positive control. Liver damage was assessed by determining hepatic histopathology and liver marker enzymes in serum. Enzyme and non-enzyme antioxidant levels and lipid peroxide content were measured in the liver. Cytochrome P450 2E1(CYP2E1) protein expression was measured via immunohistochemical staining. Nuclear factor E2-related factor(Nrf2), heme oxygenase-1(HO-1), NAD(P)H quinine oxidoreductase 1(NQO1), and γ-glutamylcysteine synthetase catalytic subunit(γ-GCSc) protein expression was measured by Western blot.RESULTS Our results showed that CDAE exhibited a strong antioxidant activity in vitro. CDAE scavenged DPPH and ABTS radicals in a dose-dependent manner. CDAE inhibited lipid peroxidation with a lipid peroxide inhibition rate of 40.6% ± 5.2%. In the FTC and TBA assays, CDAE significantly inhibited lipid peroxidation(P < 0.01). In vivo histopathological studies indicated that CCl4-induced liver injury was alleviated following CDAE treatment in rats of both sexes. CDAE(160 and 320 mg/kg) significantly prevented CCl4-induced elevations of alkaline phosphatase, glutamate pyruvate transaminase, aspartate aminotransferase, and total bilirubin levels in rats of both sexes(P < 0.05, 0.01, or 0.001). Moreover, CDAE restored the decreased activities of hepatic antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, as well as non-enzyme antioxidant glutathione, which were induced by CCl4 treatment. CDAE significantly suppressed the up-regulation of CYP2E1 and promoted Nrf2, HO-1, NQO1, and γ-GCSc protein expression.CONCLUSION CDAE exhibits good antioxidant performance in vitro, with marked radical-scavenging and anti-lipid peroxidation activities. CDAE is effective in preventing CCl4-induced hepatic damage in rats of both sexes. The hepatoprotective activity of CDAE may be attributable to its antioxidant activity, which may involve Keap1-Nrf2-mediated antioxidant regulation.展开更多
A nickel-catalyzed direct hydromonofluoromethylation of unactivated olefins with industrial raw fluoroiodomethane is developed,furnishing various primary alkyl fluorides in a step-economic manner.The key factor to suc...A nickel-catalyzed direct hydromonofluoromethylation of unactivated olefins with industrial raw fluoroiodomethane is developed,furnishing various primary alkyl fluorides in a step-economic manner.The key factor to success is the use of pyridine-oxazoline as ligand and(MeO)_(2)MeSiH as the hydrogen source.This transformation demonstrates high efficiency,mild conditions,good functional-group compatibility and great potential in the drug discovery.展开更多
A new approach for radical cross coupling of organic halides and oxalates toward esters has been developed via photoredox nickel dual catalysis.This method has been demonstrated for transformation of a wide range of a...A new approach for radical cross coupling of organic halides and oxalates toward esters has been developed via photoredox nickel dual catalysis.This method has been demonstrated for transformation of a wide range of aryl,heteroaryl,alkenyl,and alkyl bromides to various esters under mild conditions.Notably,fluoro-,chloro-,or iodo-substituents on the aryl bromides remain after the coupling reaction,which has been applied for the easy synthesis of drug molecules from simple aryl dihalides.Mechanistic studies indicate that an(alkoxycarbonyl)Ni(I)species might be generated via oxidation of Ni(0)species with an alkoxycarbonyl radical intermediate.Selective alkoxycarbonyl radical coupling over decarboxylative alkyl radical coupling is achieved here.展开更多
Background:In addition to providing free hepatitis B vaccine(HBvacc)series to all infants in China since 2005,the national programme on prevention of mother-to-child transmission(PMTCT)of hepatitis B virus(HBV)started...Background:In addition to providing free hepatitis B vaccine(HBvacc)series to all infants in China since 2005,the national programme on prevention of mother-to-child transmission(PMTCT)of hepatitis B virus(HBV)started providing free hepatitis B immunoglobulin for all new-borns born to hepatitis B surface-antigen(HBsAg)positive mothers in 2010.However,few studies have evaluated the effectiveness of the PMTCT programme.Therefore,we aimed to investigate the outcomes of the programme and identify associated factors.Method:Using a cross-sectional study design,we collected data on 4112 pairs of HBsAg-positive mothers and their children aged 7-22 months in four representative provinces through interviews and medical record review.We tested HBsAg and hepatitis B surface antibody(anti-HBs)of children by enzyme-linked immunosorbent assay at designated maternal and child hospital laboratories.We used logistic regression to analyse factors associated with child HBsAg and anti-HBs positivity.Results:Thirty-five children were HBsAg positive,indicating the mother-to-child transmission(MTCT)rate was 0.9%(0.6-1.1%).The anti-HBs positive rate was 96.8%(96.3-97.4%).Children receiving HBvacc between 12 and 24h of birth were 2.9 times more likely to be infected than those vaccinated in less than 12 h(adjusted odds ratio[aOR]=2.9,95%confidence interval[CI]:1.4-63,P=0.01).Maternal hepatitis B e-antigen(HBeAg)positivity was associated with higher MTCT rate(aOR=79.1,95%Cl:10.8-580.2,P<0.001)and lower anti-HBs positive rate(aOR=0.4,95%CI:03-0.6,P<0.001).Children with low birth weight(LBW)were 60%less likely to be anti-HBs positive than those with normal birth weight(aOR=0A,95%CI:02-0.8,P=0.01).Conclusions:The MTCT rate was lower than the 2030 WHO elimination goal,which implies the programme is on track to achieve this target.As earlier HBvacc birth dose(HBvcc-BD)was associated with lower MTCT rate,we suggest that the PMTCT programme work with the Expanded Programme on Immunization(EPI)to modify the current recommendation for early HBvcc-BD to a requirement Our finding that LBW was associated with lower anti-HBs positivity points to the need for further studies to understand factors associated with these risks and opportunities for program strengthening.The programme needs to ensure providing essential test to identify HBeAg-positive mothers and their infants and provide them with appropriate medical care and follow-up.展开更多
Photocatalytic olefin oxidation using air as an oxidant is an environmentally friendly method for producing epoxides. Covalent organic frameworks(COFs) have emerged as promising photocatalysts in various organic synth...Photocatalytic olefin oxidation using air as an oxidant is an environmentally friendly method for producing epoxides. Covalent organic frameworks(COFs) have emerged as promising photocatalysts in various organic synthesis reactions. The combination of tri-(2-pyridinal aldehyde)-containing precursor with 4,4’,4’’-(1,3,5-triazine-2,4,6-triyl)trianiline generated(N^N)-I-COF. Via imine-to-quinoline transformation and coordination anchorage of Ru(N^N)_(3)unit, Ru(N^N)_(3)@Q-COF was obtained with improved chemical stability, skeleton conjugation, and novel photochemical characteristics, and demonstrated excellent photocatalytic activity in olefin epoxidation with a wide range of substrates. The presence of H_(2)O played a crucial role in the formation of reactive oxygen species(ROSs), which in turn influenced the olefin oxidation process. The hydrophilicity of Ru(N^N)_(3) facilitated the approach of H_(2)O and O_(2) to the photogenerated charges, thereby promoting ROSs generation. The lipophilicity of Q-COF allowed for the absorption of olefin substrates, and its nano-channels increased encountering possibility between olefins and ROSs. Consequently, Ru(N^N)_(3)@Q-COF provided an intriguing platform for olefin photooxidation and could be recycled multiple times without any degradation in performance. This report revealed that the conversion of classical ROSs into less potent oxidants with rapid kinetic rates played a crucial role in achieving highly efficient and selective epoxidation of terminal olefins.展开更多
文摘AIM: To investigate the changes in clinical symptoms and gastric emptying and their association in functional dyspepsia(FD) patients.METHODS: Seventy FD patients were enrolled and divided into 2 groups Helicobacter pylori(H. pylori)-negative group(28 patients), and H. pylori-positive group(42 patients). Patients in the H. pylori-positive group were further randomly divided into groups: H. pylori-treatment group(21 patients) and conventional treatment group(21 patients). Seventy two healthy subjects were selected as the control group. The proximal and distal stomach area was measured by ultrasound immediately after patients took the test meal, and at 20, 40, 60 and 90 min; then, gastric half-emptying time was calculated. The incidence of symptoms and gastric half-emptying time between the FD and control groups were compared. The H. pylori-negative and conventional treatment groups were givenconventional treatment: domperidone 0.6 mg/(kg/d) for 1 mo. The H. pylori-treatment group was given H. pylori eradication treatment + conventional treatment: lansoprazole 30 mg once daily, clarithromycin 0.5 g twice daily and amoxicillin 1.0 g twice daily for 1 wk, then domperidone 0.6 mg/(kg/d) for 1 mo. The incidence of symptoms and gastric emptying were compared between the FD and control groups. The relationship between dyspeptic symptoms and gastric half-emptying time in the FD and control groups were analyzed. Then total symptom scores before and after treatment and gastric half-emptying time were compared among the 3 groups. RESULTS: The incidence of abdominal pain, epigastric burning sensation, abdominal distension, nausea, belching, and early satiety symptoms in the FD group were significantly higher than in the control group(50.0% vs 20.8%; 37.1% vs 12.5%; 78.6% vs 44.4%; 45.7% vs 22.2%; 52.9% vs 15.3%; 57.1% vs 19.4%; all P < 0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the FD group were slower than in the control group(93.7 ± 26.2 vs 72.0 ± 14.3; 102.2 ± 26.4 vs 87.5 ± 18.2; 102.1 ± 28.6 vs 78.3 ± 14.1; all P < 0.05). Abdominal distension, belching and early satiety had an effect on distal gastric half-emptying time(P < 0.05). Abdominal distension and abdominal pain had an effect on the gastric half-emptying time of the whole stomach(P < 0.05). All were risk factors(odds ratio > 1). The total symptom score of the 3 groups after treatment was lower than before treatment(P < 0.05). Total symptom scores after treatment in the H. pylori-treatment group and H. pylori-negative group were lower than in the conventional treatment group(5.15 ± 2.27 vs 7.02 ± 3.04, 4.93 ± 3.22 vs 7.02 ± 3.04, All P < 0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the H. pylori-negative and H. pylori-treatment groups were shorter than in the conventional treatment group(P < 0.05). CONCLUSION: FD patients have delayed gastric emptying. H. pylori infection treatment helps to improve symptoms of dyspepsia and is a reasonable choice for treatment in clinical practice.
文摘BACKGROUND Autism is the most common clinical developmental disorder in children.The childhood autism rating scale(CARS)and autistic autism behavior checklist(ABC)are the most commonly used assessment scales for diagnosing autism.However,the diagnostic validations and the corresponding cutoffs for CARS and ABC in individuals with suspected autism spectrum disorder(ASD)remain unclear.Furthermore,for suspected ASD in China,it remains unclear whether CARS is a better diagnostic tool than ABC.Also unclear is whether the current cutoff points for ABC and CARS are suitable for the accurate diagnosis of ASD.AIM To investigate the diagnostic validity of CARS and ABC based on a large Chinese sample.METHODS A total of 591 outpatient children from the ASD Unit at Beijing Children’s Hospital between June and November 2019 were identified.First,the Clancy autism behavior scale(CABS)was used to screen out suspected autism from these children.Then,each suspected ASD was evaluated by CARS and ABC.Receiver operating characteristic(ROC)curve analysis was used to compare diagnostic validations.We also calculated the area under the curve(AUC)for both CARS and ABC.RESULTS We found that the Cronbach alpha coefficients of CARS and ABC were 0.772 and 0.426,respectively.Therefore,the reliability of the CARS was higher than that of the ABC.In addition,we found that the correlation between CARS and CABS was 0.732.Next,we performed ROC curve analysis for CARS and ABC,which yielded AUC values of 0.846 and 0.768,respectively.The cutoff value,which is associated with the maximum Youden index,is usually applied as a decision threshold.We found that the cutoff values of CARS and ABC were 34 and 67,respectively.CONCLUSION This result indicated that CARS is superior to ABC in the Chinese population with suspected ASD.
文摘Intrahepatic cholangiocarcinoma(ICC)is a relatively rare form of liver cancer with a poor prognosis.The therapeutic options for patients with advanced ICC are limited and usually ineffective.There is currently no approved targeted therapy for ICC,although accumulating evidence supports inhibition of the PI3K/Akt/m TOR signaling pathway as a promising therapeutic strategy in the treatment of ICC.Here,we report a patient with stage IV ICC harboring a PIK3 CA mutation who responded well to the m TOR inhibitor everolimus.Computed tomography and magnetic resonance imaging demonstrated shrinkage of the tumor and maintenance of a partial response for 6.5 mo after everolimus treatment as the best response.To the best of our knowledge,this is the first clinical case report in the literature of clinical benefit from everolimus treatment in an ICC patient with PIK3 CA mutation.
文摘Acute kidney injury(AKI)is a clinical syndrome characterized by a rapid deterioration in kidney function and has a significant impact on patient health and survival.Mesenchymal stem cells(MSCs)have the potential to enhance renal function by suppressing the expression of cell cycle inhibitors and reducing the expression of senescence markers and microRNAs via paracrine and endocrine mechanisms.MSC-derived exosomes can alleviate AKI symptoms by regulating DNA damage,apoptosis,and other related signaling pathways through the delivery of proteins,microRNAs,long-chain noncoding RNAs,and circular RNAs.This technique is both safe and effective.MSC-derived exosomes may have great application prospects in the treatment of AKI.Understanding the underlying mechanisms will foster the development of new and promising therapeutic strategies against AKI.This review focused on recent advancements in the role of MSCs in AKI repair as well as the mechanisms underlying the role of MSCs and their secreted exosomes.It is anticipated that novel and profound insights into the functionality of MSCs and their derived exosomes will emerge.
文摘AIM: To investigate whether bone marrow-derived denritic cells pulsed with tumor lysates induce immunity against gastric cancer ex vivo. METHODS: c-kit+ hematopoietic progenitor cells were magnetically isolated with a MiniMACS separator from BALB/c mice bone marrow cells. These cells were cultured with cytokines GM-CSF, IL-4, and TNFα to induce their maturation. They were analysed by morphological observation, phenotype analysis, and mixed lymphocyte reaction (MLR). Bone marrowderived DCs (BM-DCs) were pulsed with tumor cell lysate obtained by rapid freezing and thawing at a 1:3 DC:tumor cell ratio. Finally, cytotoxic T lymphocyte (CTL) activity and interferon gamma (IFNγ) secretion was evaluated ex vivo. RESULTS: c-kit^+ hematopoietic progenitor cells from mice bone marrow cells cultured with cytokines for 8 d showed the character of typical mature DCs.Morphologically, observed by light microscope, these cells were large with oval or irregularly shaped nuclei and with many small dendrites. Phenotypically, FACS analysis showed that they expressed.high levels of la, DEC-205, CD11b, CD80 and CD86 antigen, moderate levels of CD40, and negative for F4/80. Functionally, these cells gained the capacity to stimulate allogeneic T cells in MLR assay. However, immature DCs cultured with cytokines for 5 d did not have typical DCs phenotypic markers and could not stimulate allogeneic T cells. Ex vivo primed T cells with SGC-7901 tumor cell lysate-pulsed (TP) DCs were able to induce effective CTL activity against SGC-7901 tumor cells (E:T = 100:1, 69.55% ± 6.05% specific lysis), but not B16 tumor cells, and produced higher levels of IFNγ, when stimulated with SGC-7901 tumor cells but not when stimulated with B16 tumor cells (1575.31 ± 60.25 pg/mL in SGC-7901 group vs 164.11± 18.52 pg/mL in B16 group, P 〈 0.01). CONCLUSION: BM-derived DCs pulsed with tumor lysates Can induce anti-tumor immunity specific to gastric cancer ex vivo.
基金Supported by National Science and Technology Major New Drugs Project of China,No.2012ZX09103201-012
文摘AIM To investigate the antioxidant and hepatoprotective effects of Cortex Dictamni aqueous extract(CDAE) in carbon tetrachloride(CCl4)-induced liver damage in rats.METHODS The in vitro antioxidant effect of CDAE was investigated using α,α-diphenyl-β-picrylhydrazyl(DPPH), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)(ABTS), β-carotene bleaching, reducing power, and thiobarbituric acid reactive substance assays. A linoleic acid system, including ferric thiocyanate(FTC) and thiobarbituric acid(TBA) assays, was used to evaluate the inhibition of lipid peroxidation. The in vivo hepatoprotective and antioxidant effects of CDAEagainst CCl4-induced liver damage were evaluated in Sprague-Dawley rats. Silymarin was used as a positive control. Liver damage was assessed by determining hepatic histopathology and liver marker enzymes in serum. Enzyme and non-enzyme antioxidant levels and lipid peroxide content were measured in the liver. Cytochrome P450 2E1(CYP2E1) protein expression was measured via immunohistochemical staining. Nuclear factor E2-related factor(Nrf2), heme oxygenase-1(HO-1), NAD(P)H quinine oxidoreductase 1(NQO1), and γ-glutamylcysteine synthetase catalytic subunit(γ-GCSc) protein expression was measured by Western blot.RESULTS Our results showed that CDAE exhibited a strong antioxidant activity in vitro. CDAE scavenged DPPH and ABTS radicals in a dose-dependent manner. CDAE inhibited lipid peroxidation with a lipid peroxide inhibition rate of 40.6% ± 5.2%. In the FTC and TBA assays, CDAE significantly inhibited lipid peroxidation(P < 0.01). In vivo histopathological studies indicated that CCl4-induced liver injury was alleviated following CDAE treatment in rats of both sexes. CDAE(160 and 320 mg/kg) significantly prevented CCl4-induced elevations of alkaline phosphatase, glutamate pyruvate transaminase, aspartate aminotransferase, and total bilirubin levels in rats of both sexes(P < 0.05, 0.01, or 0.001). Moreover, CDAE restored the decreased activities of hepatic antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, as well as non-enzyme antioxidant glutathione, which were induced by CCl4 treatment. CDAE significantly suppressed the up-regulation of CYP2E1 and promoted Nrf2, HO-1, NQO1, and γ-GCSc protein expression.CONCLUSION CDAE exhibits good antioxidant performance in vitro, with marked radical-scavenging and anti-lipid peroxidation activities. CDAE is effective in preventing CCl4-induced hepatic damage in rats of both sexes. The hepatoprotective activity of CDAE may be attributable to its antioxidant activity, which may involve Keap1-Nrf2-mediated antioxidant regulation.
基金National Natural Science Foundation of China(No.21971228)for financial support。
文摘A nickel-catalyzed direct hydromonofluoromethylation of unactivated olefins with industrial raw fluoroiodomethane is developed,furnishing various primary alkyl fluorides in a step-economic manner.The key factor to success is the use of pyridine-oxazoline as ligand and(MeO)_(2)MeSiH as the hydrogen source.This transformation demonstrates high efficiency,mild conditions,good functional-group compatibility and great potential in the drug discovery.
基金the financial support from the NSFC of China(21772208 and 21633013)Natural Science Foundation of Jiangsu Province(BK20201183)the Key Research Program of Frontier Sciences of Chinese Academy of Sciences(QYZDJSSW-SLH051).
文摘A new approach for radical cross coupling of organic halides and oxalates toward esters has been developed via photoredox nickel dual catalysis.This method has been demonstrated for transformation of a wide range of aryl,heteroaryl,alkenyl,and alkyl bromides to various esters under mild conditions.Notably,fluoro-,chloro-,or iodo-substituents on the aryl bromides remain after the coupling reaction,which has been applied for the easy synthesis of drug molecules from simple aryl dihalides.Mechanistic studies indicate that an(alkoxycarbonyl)Ni(I)species might be generated via oxidation of Ni(0)species with an alkoxycarbonyl radical intermediate.Selective alkoxycarbonyl radical coupling over decarboxylative alkyl radical coupling is achieved here.
文摘Background:In addition to providing free hepatitis B vaccine(HBvacc)series to all infants in China since 2005,the national programme on prevention of mother-to-child transmission(PMTCT)of hepatitis B virus(HBV)started providing free hepatitis B immunoglobulin for all new-borns born to hepatitis B surface-antigen(HBsAg)positive mothers in 2010.However,few studies have evaluated the effectiveness of the PMTCT programme.Therefore,we aimed to investigate the outcomes of the programme and identify associated factors.Method:Using a cross-sectional study design,we collected data on 4112 pairs of HBsAg-positive mothers and their children aged 7-22 months in four representative provinces through interviews and medical record review.We tested HBsAg and hepatitis B surface antibody(anti-HBs)of children by enzyme-linked immunosorbent assay at designated maternal and child hospital laboratories.We used logistic regression to analyse factors associated with child HBsAg and anti-HBs positivity.Results:Thirty-five children were HBsAg positive,indicating the mother-to-child transmission(MTCT)rate was 0.9%(0.6-1.1%).The anti-HBs positive rate was 96.8%(96.3-97.4%).Children receiving HBvacc between 12 and 24h of birth were 2.9 times more likely to be infected than those vaccinated in less than 12 h(adjusted odds ratio[aOR]=2.9,95%confidence interval[CI]:1.4-63,P=0.01).Maternal hepatitis B e-antigen(HBeAg)positivity was associated with higher MTCT rate(aOR=79.1,95%Cl:10.8-580.2,P<0.001)and lower anti-HBs positive rate(aOR=0.4,95%CI:03-0.6,P<0.001).Children with low birth weight(LBW)were 60%less likely to be anti-HBs positive than those with normal birth weight(aOR=0A,95%CI:02-0.8,P=0.01).Conclusions:The MTCT rate was lower than the 2030 WHO elimination goal,which implies the programme is on track to achieve this target.As earlier HBvacc birth dose(HBvcc-BD)was associated with lower MTCT rate,we suggest that the PMTCT programme work with the Expanded Programme on Immunization(EPI)to modify the current recommendation for early HBvcc-BD to a requirement Our finding that LBW was associated with lower anti-HBs positivity points to the need for further studies to understand factors associated with these risks and opportunities for program strengthening.The programme needs to ensure providing essential test to identify HBeAg-positive mothers and their infants and provide them with appropriate medical care and follow-up.
基金supported by the National Natural Science Foundation of China (21971011, 21831001)。
文摘Photocatalytic olefin oxidation using air as an oxidant is an environmentally friendly method for producing epoxides. Covalent organic frameworks(COFs) have emerged as promising photocatalysts in various organic synthesis reactions. The combination of tri-(2-pyridinal aldehyde)-containing precursor with 4,4’,4’’-(1,3,5-triazine-2,4,6-triyl)trianiline generated(N^N)-I-COF. Via imine-to-quinoline transformation and coordination anchorage of Ru(N^N)_(3)unit, Ru(N^N)_(3)@Q-COF was obtained with improved chemical stability, skeleton conjugation, and novel photochemical characteristics, and demonstrated excellent photocatalytic activity in olefin epoxidation with a wide range of substrates. The presence of H_(2)O played a crucial role in the formation of reactive oxygen species(ROSs), which in turn influenced the olefin oxidation process. The hydrophilicity of Ru(N^N)_(3) facilitated the approach of H_(2)O and O_(2) to the photogenerated charges, thereby promoting ROSs generation. The lipophilicity of Q-COF allowed for the absorption of olefin substrates, and its nano-channels increased encountering possibility between olefins and ROSs. Consequently, Ru(N^N)_(3)@Q-COF provided an intriguing platform for olefin photooxidation and could be recycled multiple times without any degradation in performance. This report revealed that the conversion of classical ROSs into less potent oxidants with rapid kinetic rates played a crucial role in achieving highly efficient and selective epoxidation of terminal olefins.