Objective: As laparoscopic surgery is widely applied for primarily treated gastric cancer(GC)/gastroesophageal junction cancer(GEJC) and gains many advantages, the feasibility of laparoscopic total gastrectomy(LTG) fo...Objective: As laparoscopic surgery is widely applied for primarily treated gastric cancer(GC)/gastroesophageal junction cancer(GEJC) and gains many advantages, the feasibility of laparoscopic total gastrectomy(LTG) for GC/GEJC patients who have received preoperative therapy(PT) has come to the fore. This study aims to analyze the safety and feasibility of LTG after PT for GC/GEJC patients.Methods: We retrospectively analyzed the data of 511 patients with GC/GEJC undergoing LTG, of which 405received LTG(LTG group) and 106 received PT+LTG(PT-LTG group) at Nanfang Hospital between June 2018and September 2022. The surgical outcomes were compared between the two groups.Results: The surgical duration was significantly longer in the PT-LTG group(P<0.001), while the incidence of intraoperative complications(P=1.000), postoperative complications(LTG group vs. PT-LTG group: 26.2% vs.23.6%, P=0.587), the classification of complication severity(P=0.271), and postoperative recovery was similar between two groups. Notably, the incidence of anastomotic complications of esophagojejunostomy was also comparable between the two groups(LTG group vs. PT-LTG group: 5.9% vs. 5.7%, P=0.918). The univariate and multivariate analysis confirmed that positive proximal margin [positive vs. negative: odds ratio(OR)=14.094, 95%confidence interval(95% CI): 2.639-75.260, P=0.002], rather than PT, has an impact on anastomotic complications after LTG(OR=0.945, 95% CI: 0.371-2.408, P=0.905).Conclusions: PT did not increase the surgical risk of LTG for GC/GEJC. Therefore, considering the positive effect of PT on long-term survival, the broader application of PT and LTG for GC/GEJC is supported by our findings.展开更多
Objective:The proximal margin(PM)distance for distal gastrectomy(DG)of gastric cancer(GC)remains controversial.This study investigated the prognostic value of PM distance for survival outcomes,and aimed to combine cli...Objective:The proximal margin(PM)distance for distal gastrectomy(DG)of gastric cancer(GC)remains controversial.This study investigated the prognostic value of PM distance for survival outcomes,and aimed to combine clinicopathologic variables associated with survival outcomes after DG with different PM distance for GC into a prediction nomogram.Methods:Patients who underwent radical DG from June 2004 to June 2014 at Department of General Surgery,Nanfang Hospital,Southern Medical University were included.The first endpoints of the prognostic value of PM distance(assessed in 0.5 cm increments)for disease-free survival(DFS)and overall survival(OS)were assessed.Multivariate analysis by Cox proportional hazards regression was performed using the training set,and the nomogram was constructed,patients were chronologically assigned to the training set for dates from June 1,2004 to January 30,2012(n=493)and to the validation set from February 1,2012 to June 30,2014(n=211).Results:Among 704 patients with p TNM stage I,p TNM stage II,T1-2,T3-4,N0,differentiated type,tumor size≤5.0 cm,a PM of(2.1-5.0)cm vs.PM≤2.0 cm showed a statistically significant difference in DFS and OS,while a PM>5.0 cm was not associated with any further improvement in DFS and OS vs.a PM of 2.1-5.0 cm.In patients with p TNM stage III,N1,N2-3,undifferentiated type,tumor size>5.0 cm,the PM distance was not significantly correlated with DFS and OS between patients with a PM of(2.1-5.0)cm and a PM≤2 cm,or between patients with a PM>5.0 cm and a PM of(2.1-5.0)cm,so there were no significant differences across the three PM groups.In the training set,the C-indexes of DFS and OS,were 0.721 and 0.735,respectively,and in the validation set,the C-indexes of DFS and OS,were 0.752 and 0.751,respectively.Conclusions:It is necessary to obtain not less than 2.0 cm of PM distance in early-stage disease,while PM distance was not associated with long-term survival in later and more aggressive stages of disease because more advanced GC is a systemic disease.Different types of patients should be considered for removal of an individualized PM distance intra-operatively.We developed a universally applicable prediction model for accurately determining the 1-year,3-year and 5-year DFS and OS of GC patients according to their preoperative clinicopathologic characteristics and PM distance.展开更多
Postoperative adjuvant chemotherapy(ACT)confers superior gastric cancer(GC)survival in the Eastern cohort.However,is the current standard of ACT already excessive,or is it still necessary to increase its intensity for...Postoperative adjuvant chemotherapy(ACT)confers superior gastric cancer(GC)survival in the Eastern cohort.However,is the current standard of ACT already excessive,or is it still necessary to increase its intensity for specific subgroups?Tailored ACT strategies for GC depend on gradual exploration by clinical trials in selected patients.Thus,understanding the implications of previous and current research can help us respond wisely and design effective,rational trials,save medical resources and make better decisions in clinical practice.After reviewing and analyzing studies on ACT for GC patients undergoing curative resection,we found that research strategies for conducting"addition""ACT for specific stages of the disease have achieved great progress in making ACT more tailored and personalized in consideration of pathology stages.Furthermore,trials indicate that"addition"ACT strategies for GC patient subgroups based on histological characteristics might be helpful to move toward a more specific tailored and personalized management approach.Designing ACT research focused on different node statuses should also be conducted according to the biological specificity of lymph node(LN)metastasis.Therefore,future trials designed to determine tailored treatment based on histological and biological characteristics for specific subgroups are urgently needed and conducted as the theme of the 2019 American Society of Clinical Oncology(ASCO):Caring for Every Patient,Learning from Every Patient.展开更多
Objective: This study aimed to determine the impact of type 2 diabetes mellitus(T2 DM) on clinical outcomes of gastric cancer(GC) patients and explore whether metformin use and good glycemic control could reverse it.M...Objective: This study aimed to determine the impact of type 2 diabetes mellitus(T2 DM) on clinical outcomes of gastric cancer(GC) patients and explore whether metformin use and good glycemic control could reverse it.Methods: Clinicopathologic data of consecutive GC patients who underwent gastrectomy at Nanfang Hospital between October 2004 and December 2015 were included. Propensity score matching(PSM) was performed to balance the important factors of the disease status between non-T2 DM and T2 DM group. The last follow-up time was January 2019.Results: A total of 1,692 eligible patients(1,621 non-T2 DM vs. 71 T2 DM) were included. After PSM, nonT2 DM group(n=139) and T2 DM group(n=71) were more balanced in baseline variables. The 5-year cancerspecific survival(CSS) rate in T2 DM group(47.0%) was inferior to that in non-T2 DM group(58.0%), but did not reach statistical significance [hazard ratio(HR)=1.319, 95% confidence interval(95% CI): 0.868-2.005, P=0.192].While the 5-year progress-free survival(PFS) rate of T2 DM group(40.6%) is significantly worse than that in nonT2 DM group(56.3%)(HR=1.516, 95% CI: 1.004-2.290, P=0.045). Univariate and multivariate analyses showed that T2 DM was an independent risk factor for PFS but not for CSS. In T2 DM group, metformin use subgroup was associated with superior 5-year CSS and PFS in compared with non-metformin use subgroup, although the difference was not statistically significant(5-year CSS: 48.0% vs. 45.4%, HR=0.680, 95% CI: 0.352-1.313,P=0.246;5-year PFS: 43.5% vs. 35.7%, HR=0.763, 95% CI: 0.400-1.454, P=0.406). The 5-year CSS rate was47.5% in good glycemic control subgroup and 44.1% in poor glycemic control subgroup(HR=0.826, 95% CI:0.398-1.713, P=0.605). And both two subgroups yielded a similar 5-year PFS rate(42.2% vs. 36.3%, HR=0.908,95% CI: 0.441-1.871, P=0.792).Conclusions: DM promoted disease progress of GC after gastrectomy but had not yet led to the significant discrepancy of CSS. For GC patients with T2 DM, metformin use was associated with superior survival but without statistical significance, while better glycemic control could not improve the prognosis.展开更多
In order to improve the performance of line spectrum detection,according to the feature that the underwater target radiated noise containing stable line spectrum,the differences of the phase difference between line sp...In order to improve the performance of line spectrum detection,according to the feature that the underwater target radiated noise containing stable line spectrum,the differences of the phase difference between line spectrum and background noise,a weighted line spectrum detection algorithm based on the phase variance is proposed in frequency domain.After phase difference alignment,the phase variance of line spectrum and the phase of background noise,respectively,are small and big in frequency domain,this method utilizes the weighted statistical algorithm to cumulate the frequency spectrum based on the phase variance,which can restrain the background noise disturbance,and enhance the signal to noise ratio(SNR).The theory analysis and experimental results both verify that the proposed method can well enhance the energy of line spectrum,restrain the energy of background noise,and have better detection performance under lower SNR.展开更多
Objective: The aims of this study were to examine the influence of maternal hypoadiponectinemia on the risk of varying degrees of gestational hyperglycemia as well as on ethnic differences in circulating levels of adi...Objective: The aims of this study were to examine the influence of maternal hypoadiponectinemia on the risk of varying degrees of gestational hyperglycemia as well as on ethnic differences in circulating levels of adiponectin. Methods: A case-control study nested within a prospective cohort of healthy pregnant women compared those who developed gestational diabetes mellitus (GDM, N = 80), or had an impaired glucose challenge test (GCT) non-GDM (defined as 1hr plasma glucose >140 mg/dl after a 50-g oral glucose load when screening for GDM but did not meet the diagnostic criteria for GDM by a diagnostic oral glucose tolerance test, N = 128) to normal controls (N = 557). Concentrations of serum adiponectin were determined at entry (~17 weeks) and during the 3rd trimester. Results: With multivariable adjustment, entry hypoadiponectinemia (the lowest tertile vs. other tertiles pooled) was strongly associated with an increased risk of GDM (AOR 2.68, 95% CI 1.62 - 4.41) and with impaired GCT non-GDM (AOR 1.58, 95% CI 1.05 - 2.38). This association persisted after adjustment for pregravid BMI despite the fact that the risk in obese women with low adiponectin was higher. Similar data were obtained during the 3rd trimester. The concentration of adiponectin during the 3rd trimester was significantly lower in African Americans compared to Hispanics or Caucasians and this difference was detectable in both cases and controls (p < 0.05 or p < 0.01 for each). Conclusions: The present results identified a unique graded association between hypoadiponectinemia during early pregnancy with risk of GDM and less severe hyperglycemia non-GDM independent of maternal BMI. The relationship persisted to the 3rd trimester. African American women have lower adiponectin level than Caucasian or Hispanic women. Hypoadiponectinemia may play a significant pathophysiological role in the development of GDM and of less severe gestational hyperglycemia.展开更多
The revised funding detail is given below.“The study was supported by grants from the Key Program of the National Natural Science Foundation of China(82130093),the National Key Research and Development Program of Chi...The revised funding detail is given below.“The study was supported by grants from the Key Program of the National Natural Science Foundation of China(82130093),the National Key Research and Development Program of China(grant no.2023YFC0872600),and the National Institute for Health Research(NIHR)(grant no.16/137/109)using UK aid from the UK Government to support global health research.We also acknowledge grant from Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response(20dz2260100).The views expressed in this publication are those of the author(s)and not necessarily those of the NIHR or the UK Department of Health and Social Care.”展开更多
Background:China has experienced a COVID-19 wave caused by Omicron XBB variant starting in April 2023.Our aim is to conduct a retrospective analysis exploring the dynamics of the outbreak under counterfactual scenario...Background:China has experienced a COVID-19 wave caused by Omicron XBB variant starting in April 2023.Our aim is to conduct a retrospective analysis exploring the dynamics of the outbreak under counterfactual scenarios that combine the use of vaccines,antiviral drugs,and nonpharmaceutical interventions.Methods:We developed a mathematical model of XBB transmission in China,which has been calibrated using SARS-CoV-2 positive rates per week.Intrinsic age-specific infection-hospitalization risk,infection-ICU risk,and infection-fatality risk were used to estimate disease burdens,characterized as number of hospital admissions,ICU admissions,and deaths.Results:We estimated that in absence of behavioral change,the XBB outbreak in spring 2023 would have resulted in 0.86 billion infections(∼61%of the total population).Our counterfactual analysis shows that the synergetic effect of vaccination(70%vaccination coverage),antiviral treatment(20%receiving antiviral treatment),and moderate nonpharmaceutical interventions(20%isolation and L1 PHSMs)could reduce the number of deaths to levels close to seasonal influenza(1.17 vs.0.65 per 10,000 individuals and 5.85 vs.3.85 per 10,000 individuals aged 60+,respectively).The maximum peak prevalence of hospital and ICU admissions are estimated to be lower than the corresponding capacities(8.6 vs.10.4 per 10,000 individuals and 1.2 vs.2.1 per 10,000 individuals,respectively).Conclusion:Our findings suggest that the capacity of the Chinese healthcare system was adequate to face the Omicron XBB wave in spring 2023 but,at the same time,supports the importance of administering highly effective vaccine with long-lasting immune response,and the use of antiviral treatments.展开更多
The large yellow croaker (Larimichthys crocea) is an economically important marine species with the highest annual production among the farmed marine fishes in China. However, the aquaculture industry of this species ...The large yellow croaker (Larimichthys crocea) is an economically important marine species with the highest annual production among the farmed marine fishes in China. However, the aquaculture industry of this species is suffering from severe problems that include weakened disease resistance, decreased growth rate, and reduced meat quality due to frequent inbreeding. Genome editing, which has a huge potential for solving those problems by introducing favorable genetic changes, is not yet available for the large yellow croaker. Here, we pioneered the techniques of embryo microinjection and genome editing using the CRISPR/Cas9 system in this species. Recombinant plasmids encoding green fluorescent protein (GFP) were introduced into the fertilized eggs of L. crocea by microinjection before the chorion had hardened. A high survival rate (40%) and GFP-positive larvae rate (81.8%) were achieved, indicating that the microinjection technique in L. crocea was successfully established. On this basis, Cas9 mRNA and sgRNA targeting the tyrosinase a gene in L. crocea (Lc-tyra) were co-injected into fertilized eggs of L. crocea. Mutant individuals with insertion and deletion mutations of Lc-tyra were detected. These results indicated that the CRISPR/Cas9-based genome editing technology established herein could efficiently introduce mutations at a specific site in the L. crocea genome. This method provides the potential for genetic improvement and functional genomic study in this species. This is the first report on effective CRISPR/Cas9-based genome editing in L. crocea.展开更多
Summary What is already known about this topic?Previous studies have reported vaccine efficacy or effectiveness against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron subvariants for several vaccin...Summary What is already known about this topic?Previous studies have reported vaccine efficacy or effectiveness against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron subvariants for several vaccine platforms.However,there are currently few data on estimates of inactivated platform coronavirus disease 2019(COVID-19)vaccines,especially against the globally dominant subvariant—Omicron BA.5.展开更多
In order to obtain the robust high-resolution beamforming, a high order cross sensor processing(CSP) approach is developed. According to the relation ship between the target bearing and the phase difference of each el...In order to obtain the robust high-resolution beamforming, a high order cross sensor processing(CSP) approach is developed. According to the relation ship between the target bearing and the phase difference of each element receiving signal, this method exploits the property that the same diagonal of covariance matrix with the same phase difference and obtains(2M-1)(N-1)virtual elements(N is the original array number) by executing M order CSP. The extended virtual elements can effectively increase the physical aperture of linear array, reduce the main lobe width of beam-forming, and improve the bearing resolution. The CSP method accumulates the data on the same sub-diagonal of the covariance matrix, which can decrease the impact of background noise on beam-forming. The theoretical analysis and experimental results both show that this method has high resolution in bearing estimation, compared with the MUSIC method, which has better robustness under the lower signal-to-noise ratio(SNR).展开更多
Background: Previous studies have revealed that diabetes mellitus (DM) promotes disease progress of gastric cancer (GC). This study aimed to further investigating whether DM advanced lymph nodes (LNs) metastasis in GC...Background: Previous studies have revealed that diabetes mellitus (DM) promotes disease progress of gastric cancer (GC). This study aimed to further investigating whether DM advanced lymph nodes (LNs) metastasis in GC.Methods: The clinicopathologic data of GC patients with >15 examined LN (ELN) between October 2004 and December 2019 from a prospectively maintained database were included. The observational outcomes included the number (N3b status) and anatomical distribution (N3 stations) of metastatic LN (MLN).Results: A total of 2142 eligible patients were included in the study between October 2004 and December 2019. N3 stations metastasis (26.8% in DMvs. 19.3% in non-DM,P = 0.026) and N3b status (18.8% in DMvs. 12.8% in non-DM,P = 0.039) were more advanced in the DM group, and multivariate logistic regression analyses confirmed that DM was an independent factor of developing N3 stations metastasis (odds ratio [OR] = 1.771,P= 0.011) and N3b status (OR= 1.752,P= 0.028). Also, multivariate analyses determined DM was independently associated with more MLN (β = 1.424,P = 0.047). The preponderance of N3 stations metastasis (DMvs. non-DM, T1-2: 2.2%vs. 4.9%, T3: 29.0%vs. 20.3%, T4a: 38.9%vs. 25.8%, T4b: 50.0%vs. 36.6%;ELN16-29: 8.6%vs. 10.4%, ELN30-44: 27.9%vs. 20.5%, ELN ≥ 45: 37.7%vs. 25.3%), N3b status (DMvs. non-DM, T1-2: 0%vs. 1.7%, T3: 16.1%vs. 5.1%, T4a: 27.8%vs. 19.1%, T4b: 44.0%vs. 28.0%;ELN16-29: 8.6%vs. 7.9%, ELN30-44: 18.0%vs. 11.8%, ELN ≥ 45: 26.4%vs. 17.3%), and the number of MLN (DMvs. non-DM, T1-2: 0.4vs. 1.1, T3: 8.6vs. 5.2, T4a: 9.7vs. 8.6, T4b: 17.0vs. 12.8;ELN16-29: 3.6vs. 4.6, ELN30-44: 5.8vs. 5.5, ELN ≥ 45: 12.0vs. 7.7) of DM group increased with the advancement of primary tumor depth stage and raising of ELN.Conclusions: DM was an independent risk factor for promoting LN metastasis. The preponderance of LN involvement in the DM group was aggravated with the advancement of tumor depth.展开更多
Rumen microbes play an important role in ruminant energy supply and animal performance.Previous studies showed that yak(Bos grunniens)rumen microbiome and fermentation differ from other ruminants.However,little is und...Rumen microbes play an important role in ruminant energy supply and animal performance.Previous studies showed that yak(Bos grunniens)rumen microbiome and fermentation differ from other ruminants.However,little is understood about the features of the rumen microbiome that make yak adapted to their unique environmental and dietary conditions.This study was to investigate the rumen microbiome and metabolome to understand how yak adapt to the coarse forage and harsh environment in the Qinghai-Tibetan plateau.Nine female Qaidam yellow cattle(Bos taurus),9 dzomo(hybrids of cattle and yak)and 9 female plateau yak(B.grunniens),about 5 to 6 years old,were used in this study.Rumen fermentation parameters,fibrolytic enzyme activities,and rumen metataxonomic were determined.Then 18(6 samples per group)were selected for rumen metagenomic and metabolome analysis.Metataxonomic analysis revealed that the rumen microbiota was significantly different among plateau yak,Qaidam yellow cattle,and dzomo(P<0.05).Metagenomic analysis displayed a larger gene pool encoding a richer repertoire of carbohydrate-active enzymes in the rumen microbiome of plateau yak and dzomo than Qaidam yellow cattle(P<0.05).Some of the genes encoding glycoside hydrolases that mediate the digestion of cellulose and hemicellulose were significantly enriched in the rumen of plateau yak than Qaidam yellow cattle,but glycoside hydrolase 57 that primarily includes amylases was abundant in Qaidam yellow cattle(P<0.05).The rumen fermentation profile differed also,Qaidam yellow cattle having a higher molar proportion of acetate but a lower molar proportion of propionate than dzomo and plateau yak(P<0.05).Based on metabolomic analysis,rumen microbial metabolic pathways and metabolites were different.Differential metabolites are mainly amino acids,carboxylic acids,sugars,and bile acids.Changes in rumen microbial composition could explain the above results.The present study showed that the rumen microbiome of plateau yak helps its host to adapt to the Qinghai-Tibetan plateau.In particular,the plateau yak rumen microbiome has more enzymes genes involved in cellulase and hemicellulase than that of cattle,resulting higher fibrolytic enzyme activities inyak,further providing stronger fiber degradation function.展开更多
Nanosecond pulsed electric field(nsPEF)is a novel,nonthermal,and minimally invasive modality that can ablate solid tumors by inducing apoptosis.Recent animal experiments show that nsPEF can induce the immunogenic cell...Nanosecond pulsed electric field(nsPEF)is a novel,nonthermal,and minimally invasive modality that can ablate solid tumors by inducing apoptosis.Recent animal experiments show that nsPEF can induce the immunogenic cell death of hepatocellular carcinoma(HCC)and stimulate the host’s immune response to kill residual tumor cells and decrease distant metastatic tumors.nsPEF-induced immunity is of great clinical importance because the nonthermal ablation may enhance the immune memory,which can prevent HCC recurrence and metastasis.This review summarized the most advanced research on the effect of nsPEF.The possible mechanisms of how locoregional nsPEF ablation enhances the systemic anticancer immune responses were illustrated.nsPEF stimulates the host immune system to boost stimulation and prevail suppression.Also,nsPEF increases the dendritic cell loading and inhibits the regulatory responses,thereby improving immune stimulation and limiting immunosuppression in HCC-bearing hosts.Therefore,nsPEF has excellent potential for HCC treatment.展开更多
The incidence and severity of Clostridium difficile infection(CDI)have dramatically increased in the Western world in recent years.In contrast,CDI is rarely reported in China,possibly due to under-diagnosis.This artic...The incidence and severity of Clostridium difficile infection(CDI)have dramatically increased in the Western world in recent years.In contrast,CDI is rarely reported in China,possibly due to under-diagnosis.This article briefly summarizes CDI incidence,management and preventive strategies.The authors intend to raise awareness of this disease among Chinese physicians and health workers,in order to minimize the medical and economic burden of a potential epidemic in the future.展开更多
Dear Editor, Fungal infection involves the invasion of tissues by one or more species of fungi, and this is a serious problem in both medical settings and agriculture [Brown et al., 2012]. Thus, the development of eff...Dear Editor, Fungal infection involves the invasion of tissues by one or more species of fungi, and this is a serious problem in both medical settings and agriculture [Brown et al., 2012]. Thus, the development of efficient strategies for management of these infections is urgently needed [Rodriguez-Martfn et al., 2010]. Recently, a number of antifungal proteins have been reported, including AFP from Aspergillus giganteus, PAF from Penicillium chrysogenum, NAF from Penicillium nalviogense, and AnAFP from Aspergillus niger [Marx et al., 2008; Geisen 2000]. These proteins have demonstrated antifungal activity against opportunistic plant and animal pathogens, such as Fusanum sp., Botrytis sp., and Asper- gillus sp. [Meyer, 2008]. We have previously characterized an antifungal protein (PcPAF) from the culture supernatant of the fungal strain Penicillium citrinum W1, which was isolated from sediment obtained from the Southwest Indian Ocean. PcPAF is thermostable and displays antifungal activity against various pathogenic fungi, including Trichoderma viride, Fusarium oxysporum, Alternaria Iongipes, and Pae- cilomyces variotii [Wen et al., 2014]. Therefore, large-scale production of PcPAF would enable the further drug development of this compound.展开更多
Mammalian TGF-β1 plays a crucial role in maintaining immune tolerance and inhibiting autoimmunity.Although several TGF-β1 homologues have been identified in teleosts,their immunosuppressive functions remain unclear....Mammalian TGF-β1 plays a crucial role in maintaining immune tolerance and inhibiting autoimmunity.Although several TGF-β1 homologues have been identified in teleosts,their immunosuppressive functions remain unclear.Herein,we identified and characterized LcTGF-β1,a TGF-β1 homologue from the large yellow croaker(Larimichthys crocea).LcTGF-β1 possesses several features characteristic of the TGF-βsuperfamily,including an RGD integrin binding site,an RSKR tetrabasic cut site,and nine conserved cysteines in the mature peptide.The LcTGFβ1 gene was constitutively expressed in all examined tissues,with the highest expression in the spleen,which is rich in immune cells.LcTGF-β1 was significantly upregulated in the head kidney and spleen after Vibrio alginolyticus stimulation.LcTGF-β1 was also expressed in primary head kidney lymphocytes(PKLs),monocytes/macrophages(MO/Mφs),and granulocytes(PKGs),and was significantly upregulated in the MO/Mφs after lipopolysaccharide(LPS)stimulation.Recombinant LcTGF-β1 protein(rLcTGF-β1)significantly suppressed reactive oxygen species(ROS)and nitrogen oxide(NO)production in LPS-activated head kidney MO/Mφs.Furthermore,in these MO/Mφs,rLcTGF-β1 strongly inhibited the expression of pro-inflammatory cytokine(TNFα)and inducible NO synthase(iNOS),while it induced anti-inflammatory cytokines(TGF-β1 and IL-10),arginase1,and CD206.The phagocytic activity of LPS-activated MO/Mφs was also increased by rLcTGF-β1.Finally,rLcTGF-β1 significantly inhibited the proliferation of T cells(ZAP70þcells)and downregulated T-cell activation genes(CD3ζ,TCRα,and ZAP70),T-cell marker genes(CD4 and CD8),and IL-2 in PKLs.These results thus provide strong evidence that LcTGF-β1 promotes the alternative activation of head kidney MO/Mφs and inhibits T-cell proliferation in PKLs,highlighting its role in the regulation of immune response in large yellow croaker.展开更多
Pulsed electric field(PEF)is a novel energy source by which high-voltage electric pulses are used to create irreversible electroporation.PEF is non-thermal and highly tissue-dependent in which specific targeting of th...Pulsed electric field(PEF)is a novel energy source by which high-voltage electric pulses are used to create irreversible electroporation.PEF is non-thermal and highly tissue-dependent in which specific targeting of the atrial myocardium is achieved and sparing of adjacent tissues is feasible,theoretically increasing the safety of the procedure,which could potentially break the trade-off between effective lesions and collateral damage and substantially improve risk-benefit ratios in atrial fibrillation(AF)ablation.Although recently published trials have shown a clear effect of AF ablation,large-scale clinical trials are lacking.Current clinical evidence has demonstrated significant efficacy in achieving durable pulmonary vein isolation without ablation-related adverse events.However,their putative benefits regarding efficacy,efficiency,and safety remain to be proven in randomized controlled trials.展开更多
基金supported by grants from the Clinical Research Program of Nanfang Hospital, Southern Medical University (No.2021CR001 and No.2021CR013)Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer (No.2020B 121201004)“Climbing Program”, Special Fund of Guangdong Province (No.pdjh2022a0093 and No.pdjh2023a0098)。
文摘Objective: As laparoscopic surgery is widely applied for primarily treated gastric cancer(GC)/gastroesophageal junction cancer(GEJC) and gains many advantages, the feasibility of laparoscopic total gastrectomy(LTG) for GC/GEJC patients who have received preoperative therapy(PT) has come to the fore. This study aims to analyze the safety and feasibility of LTG after PT for GC/GEJC patients.Methods: We retrospectively analyzed the data of 511 patients with GC/GEJC undergoing LTG, of which 405received LTG(LTG group) and 106 received PT+LTG(PT-LTG group) at Nanfang Hospital between June 2018and September 2022. The surgical outcomes were compared between the two groups.Results: The surgical duration was significantly longer in the PT-LTG group(P<0.001), while the incidence of intraoperative complications(P=1.000), postoperative complications(LTG group vs. PT-LTG group: 26.2% vs.23.6%, P=0.587), the classification of complication severity(P=0.271), and postoperative recovery was similar between two groups. Notably, the incidence of anastomotic complications of esophagojejunostomy was also comparable between the two groups(LTG group vs. PT-LTG group: 5.9% vs. 5.7%, P=0.918). The univariate and multivariate analysis confirmed that positive proximal margin [positive vs. negative: odds ratio(OR)=14.094, 95%confidence interval(95% CI): 2.639-75.260, P=0.002], rather than PT, has an impact on anastomotic complications after LTG(OR=0.945, 95% CI: 0.371-2.408, P=0.905).Conclusions: PT did not increase the surgical risk of LTG for GC/GEJC. Therefore, considering the positive effect of PT on long-term survival, the broader application of PT and LTG for GC/GEJC is supported by our findings.
基金supported by Grant of Wu Jieping Medical Funding(No.320.2710.1819)。
文摘Objective:The proximal margin(PM)distance for distal gastrectomy(DG)of gastric cancer(GC)remains controversial.This study investigated the prognostic value of PM distance for survival outcomes,and aimed to combine clinicopathologic variables associated with survival outcomes after DG with different PM distance for GC into a prediction nomogram.Methods:Patients who underwent radical DG from June 2004 to June 2014 at Department of General Surgery,Nanfang Hospital,Southern Medical University were included.The first endpoints of the prognostic value of PM distance(assessed in 0.5 cm increments)for disease-free survival(DFS)and overall survival(OS)were assessed.Multivariate analysis by Cox proportional hazards regression was performed using the training set,and the nomogram was constructed,patients were chronologically assigned to the training set for dates from June 1,2004 to January 30,2012(n=493)and to the validation set from February 1,2012 to June 30,2014(n=211).Results:Among 704 patients with p TNM stage I,p TNM stage II,T1-2,T3-4,N0,differentiated type,tumor size≤5.0 cm,a PM of(2.1-5.0)cm vs.PM≤2.0 cm showed a statistically significant difference in DFS and OS,while a PM>5.0 cm was not associated with any further improvement in DFS and OS vs.a PM of 2.1-5.0 cm.In patients with p TNM stage III,N1,N2-3,undifferentiated type,tumor size>5.0 cm,the PM distance was not significantly correlated with DFS and OS between patients with a PM of(2.1-5.0)cm and a PM≤2 cm,or between patients with a PM>5.0 cm and a PM of(2.1-5.0)cm,so there were no significant differences across the three PM groups.In the training set,the C-indexes of DFS and OS,were 0.721 and 0.735,respectively,and in the validation set,the C-indexes of DFS and OS,were 0.752 and 0.751,respectively.Conclusions:It is necessary to obtain not less than 2.0 cm of PM distance in early-stage disease,while PM distance was not associated with long-term survival in later and more aggressive stages of disease because more advanced GC is a systemic disease.Different types of patients should be considered for removal of an individualized PM distance intra-operatively.We developed a universally applicable prediction model for accurately determining the 1-year,3-year and 5-year DFS and OS of GC patients according to their preoperative clinicopathologic characteristics and PM distance.
基金supported by the National Natural Science Foundation of China (No. 81872013)National Key Research and Development Program (No.2017YFC 0108300)+1 种基金National Key Clinical Specialty Discipline Construction Program of China (No. [2012]121)Science and Technology Planning Project of Guangdong Province (No.2017B020226005)
文摘Postoperative adjuvant chemotherapy(ACT)confers superior gastric cancer(GC)survival in the Eastern cohort.However,is the current standard of ACT already excessive,or is it still necessary to increase its intensity for specific subgroups?Tailored ACT strategies for GC depend on gradual exploration by clinical trials in selected patients.Thus,understanding the implications of previous and current research can help us respond wisely and design effective,rational trials,save medical resources and make better decisions in clinical practice.After reviewing and analyzing studies on ACT for GC patients undergoing curative resection,we found that research strategies for conducting"addition""ACT for specific stages of the disease have achieved great progress in making ACT more tailored and personalized in consideration of pathology stages.Furthermore,trials indicate that"addition"ACT strategies for GC patient subgroups based on histological characteristics might be helpful to move toward a more specific tailored and personalized management approach.Designing ACT research focused on different node statuses should also be conducted according to the biological specificity of lymph node(LN)metastasis.Therefore,future trials designed to determine tailored treatment based on histological and biological characteristics for specific subgroups are urgently needed and conducted as the theme of the 2019 American Society of Clinical Oncology(ASCO):Caring for Every Patient,Learning from Every Patient.
基金supported by the National Natural Science Foundation of China (No.81872013)Clinical Research Program of Nanfang Hospital, Southern Medical University (No.2018CR017)+1 种基金National Key Clinical Specialty Discipline Construction Program of China (No.[2012]121)Science and Technology Planning Project of Guangdong Province (No.2017B020226005)。
文摘Objective: This study aimed to determine the impact of type 2 diabetes mellitus(T2 DM) on clinical outcomes of gastric cancer(GC) patients and explore whether metformin use and good glycemic control could reverse it.Methods: Clinicopathologic data of consecutive GC patients who underwent gastrectomy at Nanfang Hospital between October 2004 and December 2015 were included. Propensity score matching(PSM) was performed to balance the important factors of the disease status between non-T2 DM and T2 DM group. The last follow-up time was January 2019.Results: A total of 1,692 eligible patients(1,621 non-T2 DM vs. 71 T2 DM) were included. After PSM, nonT2 DM group(n=139) and T2 DM group(n=71) were more balanced in baseline variables. The 5-year cancerspecific survival(CSS) rate in T2 DM group(47.0%) was inferior to that in non-T2 DM group(58.0%), but did not reach statistical significance [hazard ratio(HR)=1.319, 95% confidence interval(95% CI): 0.868-2.005, P=0.192].While the 5-year progress-free survival(PFS) rate of T2 DM group(40.6%) is significantly worse than that in nonT2 DM group(56.3%)(HR=1.516, 95% CI: 1.004-2.290, P=0.045). Univariate and multivariate analyses showed that T2 DM was an independent risk factor for PFS but not for CSS. In T2 DM group, metformin use subgroup was associated with superior 5-year CSS and PFS in compared with non-metformin use subgroup, although the difference was not statistically significant(5-year CSS: 48.0% vs. 45.4%, HR=0.680, 95% CI: 0.352-1.313,P=0.246;5-year PFS: 43.5% vs. 35.7%, HR=0.763, 95% CI: 0.400-1.454, P=0.406). The 5-year CSS rate was47.5% in good glycemic control subgroup and 44.1% in poor glycemic control subgroup(HR=0.826, 95% CI:0.398-1.713, P=0.605). And both two subgroups yielded a similar 5-year PFS rate(42.2% vs. 36.3%, HR=0.908,95% CI: 0.441-1.871, P=0.792).Conclusions: DM promoted disease progress of GC after gastrectomy but had not yet led to the significant discrepancy of CSS. For GC patients with T2 DM, metformin use was associated with superior survival but without statistical significance, while better glycemic control could not improve the prognosis.
基金supported by the National Natural Science Foundation of China(61372180)the Young Talent Frontier Project of Institute of Acoustics of Chinese Academy of Sciences(Y454341261)
文摘In order to improve the performance of line spectrum detection,according to the feature that the underwater target radiated noise containing stable line spectrum,the differences of the phase difference between line spectrum and background noise,a weighted line spectrum detection algorithm based on the phase variance is proposed in frequency domain.After phase difference alignment,the phase variance of line spectrum and the phase of background noise,respectively,are small and big in frequency domain,this method utilizes the weighted statistical algorithm to cumulate the frequency spectrum based on the phase variance,which can restrain the background noise disturbance,and enhance the signal to noise ratio(SNR).The theory analysis and experimental results both verify that the proposed method can well enhance the energy of line spectrum,restrain the energy of background noise,and have better detection performance under lower SNR.
文摘Objective: The aims of this study were to examine the influence of maternal hypoadiponectinemia on the risk of varying degrees of gestational hyperglycemia as well as on ethnic differences in circulating levels of adiponectin. Methods: A case-control study nested within a prospective cohort of healthy pregnant women compared those who developed gestational diabetes mellitus (GDM, N = 80), or had an impaired glucose challenge test (GCT) non-GDM (defined as 1hr plasma glucose >140 mg/dl after a 50-g oral glucose load when screening for GDM but did not meet the diagnostic criteria for GDM by a diagnostic oral glucose tolerance test, N = 128) to normal controls (N = 557). Concentrations of serum adiponectin were determined at entry (~17 weeks) and during the 3rd trimester. Results: With multivariable adjustment, entry hypoadiponectinemia (the lowest tertile vs. other tertiles pooled) was strongly associated with an increased risk of GDM (AOR 2.68, 95% CI 1.62 - 4.41) and with impaired GCT non-GDM (AOR 1.58, 95% CI 1.05 - 2.38). This association persisted after adjustment for pregravid BMI despite the fact that the risk in obese women with low adiponectin was higher. Similar data were obtained during the 3rd trimester. The concentration of adiponectin during the 3rd trimester was significantly lower in African Americans compared to Hispanics or Caucasians and this difference was detectable in both cases and controls (p < 0.05 or p < 0.01 for each). Conclusions: The present results identified a unique graded association between hypoadiponectinemia during early pregnancy with risk of GDM and less severe hyperglycemia non-GDM independent of maternal BMI. The relationship persisted to the 3rd trimester. African American women have lower adiponectin level than Caucasian or Hispanic women. Hypoadiponectinemia may play a significant pathophysiological role in the development of GDM and of less severe gestational hyperglycemia.
文摘The revised funding detail is given below.“The study was supported by grants from the Key Program of the National Natural Science Foundation of China(82130093),the National Key Research and Development Program of China(grant no.2023YFC0872600),and the National Institute for Health Research(NIHR)(grant no.16/137/109)using UK aid from the UK Government to support global health research.We also acknowledge grant from Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response(20dz2260100).The views expressed in this publication are those of the author(s)and not necessarily those of the NIHR or the UK Department of Health and Social Care.”
基金supported by grants from the Key Program of the National Natural Science Foundation of China(82,130,093)the National Institute for Health Research(NIHR)(grant no.16/137/109)using UK aid from the UK Government to support global health researchgrant from Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response(20dz2260100).
文摘Background:China has experienced a COVID-19 wave caused by Omicron XBB variant starting in April 2023.Our aim is to conduct a retrospective analysis exploring the dynamics of the outbreak under counterfactual scenarios that combine the use of vaccines,antiviral drugs,and nonpharmaceutical interventions.Methods:We developed a mathematical model of XBB transmission in China,which has been calibrated using SARS-CoV-2 positive rates per week.Intrinsic age-specific infection-hospitalization risk,infection-ICU risk,and infection-fatality risk were used to estimate disease burdens,characterized as number of hospital admissions,ICU admissions,and deaths.Results:We estimated that in absence of behavioral change,the XBB outbreak in spring 2023 would have resulted in 0.86 billion infections(∼61%of the total population).Our counterfactual analysis shows that the synergetic effect of vaccination(70%vaccination coverage),antiviral treatment(20%receiving antiviral treatment),and moderate nonpharmaceutical interventions(20%isolation and L1 PHSMs)could reduce the number of deaths to levels close to seasonal influenza(1.17 vs.0.65 per 10,000 individuals and 5.85 vs.3.85 per 10,000 individuals aged 60+,respectively).The maximum peak prevalence of hospital and ICU admissions are estimated to be lower than the corresponding capacities(8.6 vs.10.4 per 10,000 individuals and 1.2 vs.2.1 per 10,000 individuals,respectively).Conclusion:Our findings suggest that the capacity of the Chinese healthcare system was adequate to face the Omicron XBB wave in spring 2023 but,at the same time,supports the importance of administering highly effective vaccine with long-lasting immune response,and the use of antiviral treatments.
基金The work was supported by grants from the National Key R&D Program of China(2018YFD0900505)National Natural Science Foundation of China(U1905204 and 31802337)+1 种基金China Agricultural Research System(CARS-47)Marine Economic Development Subsidy Fund of Fujian Province(FJHJF-L-2019-2).
文摘The large yellow croaker (Larimichthys crocea) is an economically important marine species with the highest annual production among the farmed marine fishes in China. However, the aquaculture industry of this species is suffering from severe problems that include weakened disease resistance, decreased growth rate, and reduced meat quality due to frequent inbreeding. Genome editing, which has a huge potential for solving those problems by introducing favorable genetic changes, is not yet available for the large yellow croaker. Here, we pioneered the techniques of embryo microinjection and genome editing using the CRISPR/Cas9 system in this species. Recombinant plasmids encoding green fluorescent protein (GFP) were introduced into the fertilized eggs of L. crocea by microinjection before the chorion had hardened. A high survival rate (40%) and GFP-positive larvae rate (81.8%) were achieved, indicating that the microinjection technique in L. crocea was successfully established. On this basis, Cas9 mRNA and sgRNA targeting the tyrosinase a gene in L. crocea (Lc-tyra) were co-injected into fertilized eggs of L. crocea. Mutant individuals with insertion and deletion mutations of Lc-tyra were detected. These results indicated that the CRISPR/Cas9-based genome editing technology established herein could efficiently introduce mutations at a specific site in the L. crocea genome. This method provides the potential for genetic improvement and functional genomic study in this species. This is the first report on effective CRISPR/Cas9-based genome editing in L. crocea.
基金Supported by the Key Program of the National Natural Science Foundation of China(82130093)Shanghai Municipal Science and Technology Major Project(HS2021SHZX001).
文摘Summary What is already known about this topic?Previous studies have reported vaccine efficacy or effectiveness against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron subvariants for several vaccine platforms.However,there are currently few data on estimates of inactivated platform coronavirus disease 2019(COVID-19)vaccines,especially against the globally dominant subvariant—Omicron BA.5.
基金supported by the National Natural Science Foundation of China(61372180)the Young Talent Frontier Project of Institute of Acoustics of Chinese Academy of Sciences(Y454341261)
文摘In order to obtain the robust high-resolution beamforming, a high order cross sensor processing(CSP) approach is developed. According to the relation ship between the target bearing and the phase difference of each element receiving signal, this method exploits the property that the same diagonal of covariance matrix with the same phase difference and obtains(2M-1)(N-1)virtual elements(N is the original array number) by executing M order CSP. The extended virtual elements can effectively increase the physical aperture of linear array, reduce the main lobe width of beam-forming, and improve the bearing resolution. The CSP method accumulates the data on the same sub-diagonal of the covariance matrix, which can decrease the impact of background noise on beam-forming. The theoretical analysis and experimental results both show that this method has high resolution in bearing estimation, compared with the MUSIC method, which has better robustness under the lower signal-to-noise ratio(SNR).
基金Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer(No.2020B121201004)Guangdong Provincial Major Talents Project(No.2019JC05 Y361)+3 种基金Science and Technology Planning Project of Guangdong Province(No. 2017B020226005)"Climbing Program" , Special Fund of Guangdong Province(No. pdjh2021b0098)National Natural Science Foundation of China(No. 81902444)Science and Technology Program of Guangzhou(No. 201903010072)。
文摘Background: Previous studies have revealed that diabetes mellitus (DM) promotes disease progress of gastric cancer (GC). This study aimed to further investigating whether DM advanced lymph nodes (LNs) metastasis in GC.Methods: The clinicopathologic data of GC patients with >15 examined LN (ELN) between October 2004 and December 2019 from a prospectively maintained database were included. The observational outcomes included the number (N3b status) and anatomical distribution (N3 stations) of metastatic LN (MLN).Results: A total of 2142 eligible patients were included in the study between October 2004 and December 2019. N3 stations metastasis (26.8% in DMvs. 19.3% in non-DM,P = 0.026) and N3b status (18.8% in DMvs. 12.8% in non-DM,P = 0.039) were more advanced in the DM group, and multivariate logistic regression analyses confirmed that DM was an independent factor of developing N3 stations metastasis (odds ratio [OR] = 1.771,P= 0.011) and N3b status (OR= 1.752,P= 0.028). Also, multivariate analyses determined DM was independently associated with more MLN (β = 1.424,P = 0.047). The preponderance of N3 stations metastasis (DMvs. non-DM, T1-2: 2.2%vs. 4.9%, T3: 29.0%vs. 20.3%, T4a: 38.9%vs. 25.8%, T4b: 50.0%vs. 36.6%;ELN16-29: 8.6%vs. 10.4%, ELN30-44: 27.9%vs. 20.5%, ELN ≥ 45: 37.7%vs. 25.3%), N3b status (DMvs. non-DM, T1-2: 0%vs. 1.7%, T3: 16.1%vs. 5.1%, T4a: 27.8%vs. 19.1%, T4b: 44.0%vs. 28.0%;ELN16-29: 8.6%vs. 7.9%, ELN30-44: 18.0%vs. 11.8%, ELN ≥ 45: 26.4%vs. 17.3%), and the number of MLN (DMvs. non-DM, T1-2: 0.4vs. 1.1, T3: 8.6vs. 5.2, T4a: 9.7vs. 8.6, T4b: 17.0vs. 12.8;ELN16-29: 3.6vs. 4.6, ELN30-44: 5.8vs. 5.5, ELN ≥ 45: 12.0vs. 7.7) of DM group increased with the advancement of primary tumor depth stage and raising of ELN.Conclusions: DM was an independent risk factor for promoting LN metastasis. The preponderance of LN involvement in the DM group was aggravated with the advancement of tumor depth.
文摘Rumen microbes play an important role in ruminant energy supply and animal performance.Previous studies showed that yak(Bos grunniens)rumen microbiome and fermentation differ from other ruminants.However,little is understood about the features of the rumen microbiome that make yak adapted to their unique environmental and dietary conditions.This study was to investigate the rumen microbiome and metabolome to understand how yak adapt to the coarse forage and harsh environment in the Qinghai-Tibetan plateau.Nine female Qaidam yellow cattle(Bos taurus),9 dzomo(hybrids of cattle and yak)and 9 female plateau yak(B.grunniens),about 5 to 6 years old,were used in this study.Rumen fermentation parameters,fibrolytic enzyme activities,and rumen metataxonomic were determined.Then 18(6 samples per group)were selected for rumen metagenomic and metabolome analysis.Metataxonomic analysis revealed that the rumen microbiota was significantly different among plateau yak,Qaidam yellow cattle,and dzomo(P<0.05).Metagenomic analysis displayed a larger gene pool encoding a richer repertoire of carbohydrate-active enzymes in the rumen microbiome of plateau yak and dzomo than Qaidam yellow cattle(P<0.05).Some of the genes encoding glycoside hydrolases that mediate the digestion of cellulose and hemicellulose were significantly enriched in the rumen of plateau yak than Qaidam yellow cattle,but glycoside hydrolase 57 that primarily includes amylases was abundant in Qaidam yellow cattle(P<0.05).The rumen fermentation profile differed also,Qaidam yellow cattle having a higher molar proportion of acetate but a lower molar proportion of propionate than dzomo and plateau yak(P<0.05).Based on metabolomic analysis,rumen microbial metabolic pathways and metabolites were different.Differential metabolites are mainly amino acids,carboxylic acids,sugars,and bile acids.Changes in rumen microbial composition could explain the above results.The present study showed that the rumen microbiome of plateau yak helps its host to adapt to the Qinghai-Tibetan plateau.In particular,the plateau yak rumen microbiome has more enzymes genes involved in cellulase and hemicellulase than that of cattle,resulting higher fibrolytic enzyme activities inyak,further providing stronger fiber degradation function.
基金National S&T Major Project(No.2018ZX10301201)Innovative Research Groups of National Natural Science Foundation of China(No.81721091)。
文摘Nanosecond pulsed electric field(nsPEF)is a novel,nonthermal,and minimally invasive modality that can ablate solid tumors by inducing apoptosis.Recent animal experiments show that nsPEF can induce the immunogenic cell death of hepatocellular carcinoma(HCC)and stimulate the host’s immune response to kill residual tumor cells and decrease distant metastatic tumors.nsPEF-induced immunity is of great clinical importance because the nonthermal ablation may enhance the immune memory,which can prevent HCC recurrence and metastasis.This review summarized the most advanced research on the effect of nsPEF.The possible mechanisms of how locoregional nsPEF ablation enhances the systemic anticancer immune responses were illustrated.nsPEF stimulates the host immune system to boost stimulation and prevail suppression.Also,nsPEF increases the dendritic cell loading and inhibits the regulatory responses,thereby improving immune stimulation and limiting immunosuppression in HCC-bearing hosts.Therefore,nsPEF has excellent potential for HCC treatment.
基金Dr Xinhua Chen was supported by the Career Development Award of Crohn’s&Colitis Foundation of America.
文摘The incidence and severity of Clostridium difficile infection(CDI)have dramatically increased in the Western world in recent years.In contrast,CDI is rarely reported in China,possibly due to under-diagnosis.This article briefly summarizes CDI incidence,management and preventive strategies.The authors intend to raise awareness of this disease among Chinese physicians and health workers,in order to minimize the medical and economic burden of a potential epidemic in the future.
基金the Comra fund Grant (DY125-15-T-07), the National Natural Science Foundation of China (Grant Nos. 30972279 and 40976080), and the National Basic Research Program (973 Program) (No. 2015CB755903).
文摘Dear Editor, Fungal infection involves the invasion of tissues by one or more species of fungi, and this is a serious problem in both medical settings and agriculture [Brown et al., 2012]. Thus, the development of efficient strategies for management of these infections is urgently needed [Rodriguez-Martfn et al., 2010]. Recently, a number of antifungal proteins have been reported, including AFP from Aspergillus giganteus, PAF from Penicillium chrysogenum, NAF from Penicillium nalviogense, and AnAFP from Aspergillus niger [Marx et al., 2008; Geisen 2000]. These proteins have demonstrated antifungal activity against opportunistic plant and animal pathogens, such as Fusanum sp., Botrytis sp., and Asper- gillus sp. [Meyer, 2008]. We have previously characterized an antifungal protein (PcPAF) from the culture supernatant of the fungal strain Penicillium citrinum W1, which was isolated from sediment obtained from the Southwest Indian Ocean. PcPAF is thermostable and displays antifungal activity against various pathogenic fungi, including Trichoderma viride, Fusarium oxysporum, Alternaria Iongipes, and Pae- cilomyces variotii [Wen et al., 2014]. Therefore, large-scale production of PcPAF would enable the further drug development of this compound.
基金funded by the National Natural Science Foundation of China(U1905204)China Agricultural Research System of MOF and MARA(CARS-47)+1 种基金Fujian Science and Technology Department(2021N5008)Institute of Oceanology of Fuzhou(2021F02).
文摘Mammalian TGF-β1 plays a crucial role in maintaining immune tolerance and inhibiting autoimmunity.Although several TGF-β1 homologues have been identified in teleosts,their immunosuppressive functions remain unclear.Herein,we identified and characterized LcTGF-β1,a TGF-β1 homologue from the large yellow croaker(Larimichthys crocea).LcTGF-β1 possesses several features characteristic of the TGF-βsuperfamily,including an RGD integrin binding site,an RSKR tetrabasic cut site,and nine conserved cysteines in the mature peptide.The LcTGFβ1 gene was constitutively expressed in all examined tissues,with the highest expression in the spleen,which is rich in immune cells.LcTGF-β1 was significantly upregulated in the head kidney and spleen after Vibrio alginolyticus stimulation.LcTGF-β1 was also expressed in primary head kidney lymphocytes(PKLs),monocytes/macrophages(MO/Mφs),and granulocytes(PKGs),and was significantly upregulated in the MO/Mφs after lipopolysaccharide(LPS)stimulation.Recombinant LcTGF-β1 protein(rLcTGF-β1)significantly suppressed reactive oxygen species(ROS)and nitrogen oxide(NO)production in LPS-activated head kidney MO/Mφs.Furthermore,in these MO/Mφs,rLcTGF-β1 strongly inhibited the expression of pro-inflammatory cytokine(TNFα)and inducible NO synthase(iNOS),while it induced anti-inflammatory cytokines(TGF-β1 and IL-10),arginase1,and CD206.The phagocytic activity of LPS-activated MO/Mφs was also increased by rLcTGF-β1.Finally,rLcTGF-β1 significantly inhibited the proliferation of T cells(ZAP70þcells)and downregulated T-cell activation genes(CD3ζ,TCRα,and ZAP70),T-cell marker genes(CD4 and CD8),and IL-2 in PKLs.These results thus provide strong evidence that LcTGF-β1 promotes the alternative activation of head kidney MO/Mφs and inhibits T-cell proliferation in PKLs,highlighting its role in the regulation of immune response in large yellow croaker.
基金supported by National S&T Major Project(2018ZX10301201)Chinese Natural Science Foundation Grants(82027803)+3 种基金Science and Technology Development Special Fund of Shanghai Health and Family Planning Commission(ZK2019B25)Plateau Discipline Construction Fund of Pudong New Area Health and Family Planning Commission(PWYgy2018-03)Chinese Academy of Engineering(2019-ZD-6-01)Zhejiang University Education Foundation(2020XGZX063).
文摘Pulsed electric field(PEF)is a novel energy source by which high-voltage electric pulses are used to create irreversible electroporation.PEF is non-thermal and highly tissue-dependent in which specific targeting of the atrial myocardium is achieved and sparing of adjacent tissues is feasible,theoretically increasing the safety of the procedure,which could potentially break the trade-off between effective lesions and collateral damage and substantially improve risk-benefit ratios in atrial fibrillation(AF)ablation.Although recently published trials have shown a clear effect of AF ablation,large-scale clinical trials are lacking.Current clinical evidence has demonstrated significant efficacy in achieving durable pulmonary vein isolation without ablation-related adverse events.However,their putative benefits regarding efficacy,efficiency,and safety remain to be proven in randomized controlled trials.