Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not complet...Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.展开更多
The outbreak of novel coronavirus pneumonia has affected almost all industries and enterprises.This paper analyzes the impact of the epidemic on the macro economy through GDP and other indicators,analyzes the impact o...The outbreak of novel coronavirus pneumonia has affected almost all industries and enterprises.This paper analyzes the impact of the epidemic on the macro economy through GDP and other indicators,analyzes the impact of the epidemic on the overall business performance of the enterprises through the asset turnover speed index of the above scale industrial enterprises,and analyzes the impact of the epidemic on the net profit of the listed companies through the first quarter performance forecast of the listed companies.At last,the paper puts forward that enterprises should improve their awareness and ability to resist risks.展开更多
BACKGROUND Gut microbiota(GM)affects the progression and response to treatment in liver diseases.The GM composition is diverse and associated with different etiologies of liver diseases.Notably,alterations in GM alter...BACKGROUND Gut microbiota(GM)affects the progression and response to treatment in liver diseases.The GM composition is diverse and associated with different etiologies of liver diseases.Notably,alterations in GM alterations are observed in patients with portal hypertension(PH)secondary to cirrhosis,with hepatitis B virus(HBV)infection being a major cause of cirrhosis in China.Thus,understanding the role of GM alterations in patients with HBV infection-related PH is essential.AIM To evaluate GM alterations in patients with HBV-related PH after transjugular intrahepatic portosystemic shunt(TIPS)placement.METHODS This was a prospective,observational clinical study.There were 30 patients(with a 100%technical success rate)recruited in the present study.Patients with esophagogastric variceal bleeding due to HBV infection-associated PH who underwent TIPS were enrolled.Stool samples were obtained before and one month after TIPS treatment,and GM was analyzed using 16S ribosomal RNA amplicon sequencing.RESULTS One month after TIPS placement,8 patients developed hepatic encephalopathy(HE)and were assigned to the HE group;the other 22 patients were assigned to the non-HE group.There was no substantial disparity in the abundance of GM at the phylum level between the two groups,regardless of TIPS treatment(all,P>0.05).However,following TIPS placement,the following results were observed:(1)The abundance of Haemophilus and Eggerthella increased,whereas that of Anaerostipes,Dialister,Butyricicoccus,and Oscillospira declined in the HE group;(2)The richness of Eggerthella,Streptococcus,and Bilophila increased,whereas that of Roseburia and Ruminococcus decreased in the non-HE group;and(3)Members from the pathogenic genus Morganella appeared in the HE group but not in the non-HE group.CONCLUSION Intestinal microbiota-related synergism may predict the risk of HE following TIPS placement in patients with HBVrelated PH.Prophylactic microbiome therapies may be useful for preventing and treating HE after TIPS placement.展开更多
BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combinat...BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.展开更多
Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and manageme...Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.展开更多
Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the sci...Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the scientific community.Numerous trials have been conducted to develop treatment options for ZIKV infection.This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection.A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development.The results indicate that several therapeutic interventions are being tested against ZIKV infection,such as DNA vaccines,subunit vaccines,live-attenuated vaccines,virus-vector-based vaccines,inactivated vaccines,virus-like particles,and mRNA-based vaccines.In addition,approved anti-ZIKV drugs that can reduce the global burden are discussed.Although many vaccine candidates for ZIKV are at different stages of development,none of them have received Food and Drug Authority approval for use up to now.The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.展开更多
BACKGROUND Although the benefits of antiviral therapy for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)have been proven,researchers have not con-firmed the differences in patient outcomes between patien...BACKGROUND Although the benefits of antiviral therapy for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)have been proven,researchers have not con-firmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time(at least 24 wk)and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC.AIM To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC.METHODS A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi’an Jiaotong University from January 2016 to June 2019 was conducted.Considering the history of antiviral therapy,patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups.RESULTS Kaplan–Meier analysis revealed significant differences in overall survival(P<0.0001)and disease-free survival(P=0.035)between the two groups.Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival(hazard ratio=0.27;95%confidence interval:0.08-0.88;P=0.030).CONCLUSION In patients with HBV-related HCC,it is ideal to receive preoperative long-term antiviral therapy,which helps patients tolerate more extensive hepatectomy;however,remedial antiviral therapy,which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL,can also result in improved outcomes.展开更多
BACKGROUND Chronic hepatitis C virus(HCV)infection is a major global health concern that leads to liver fibrosis,cirrhosis,and cancer.Regimens containing direct-acting antivirals(DAAs)have become the mainstay of HCV t...BACKGROUND Chronic hepatitis C virus(HCV)infection is a major global health concern that leads to liver fibrosis,cirrhosis,and cancer.Regimens containing direct-acting antivirals(DAAs)have become the mainstay of HCV treatment,achieving a high sustained virological response(SVR)with minimal adverse events.CASE SUMMARY A 74-year-old woman with chronic HCV infection was treated with the DAAs ledipasvir,and sofosbuvir for 12 wk and achieved SVR.Twenty-four weeks after treatment completion,the liver enzyme and serum IgG levels increased,and antinuclear antibody became positive without HCV viremia,suggesting the development of autoimmune hepatitis(AIH).After liver biopsy indicated AIH,a definite AIH diagnosis was made and prednisolone was initiated.The treatment was effective,and the liver enzyme and serum IgG levels normalized.However,multiple strictures of the intrahepatic and extrahepatic bile ducts with dilatation of the peripheral bile ducts appeared on magnetic resonance cholangiopancreatography after 3 years of achieving SVR,which were consistent with primary sclerosing cholangitis.CONCLUSION The potential risk of developing autoimmune liver diseases after DAA treatment should be considered.展开更多
Objective This study aimed to investigate the prevalence of Epstein-Barr virus(EBV)infection in patients with and without cancer.Methods A total of 26,648 participants who underwent whole-blood EBV DNA(WBEBV)assays be...Objective This study aimed to investigate the prevalence of Epstein-Barr virus(EBV)infection in patients with and without cancer.Methods A total of 26,648 participants who underwent whole-blood EBV DNA(WBEBV)assays between January 1,2020,and August 31,2023,were included.The chi-square test was used for categorical data analysis,and R software was used to analyze the differences in EBV DNA load levels and the diagnostic capabilities of WBEBV.Results Positive rates were 10.2%and 25.4%for healthy controls(HC)and patients,respectively.The positivity rate for EBV-associated neoplasms(EN)was the highest at 7.53%,followed by leukemia(Le)at 5.49%.The subgroup analysis showed that the positivity rate for abnormal proliferation or hyperplasia(APH)was 31.9%,followed by 30.5%for Le.The WBEBV of patients with transplants(TP),especially living-related transplants(LT),was the highest among all subgroups.WBEBV at diagnosis was used to differentiate between infectious mononucleosis(IM)and chronic active Epstein-Barr virus(CAEBV),with a sensitivity of 67.4%(95%confidence interval[CI]:57.6-75.8)and specificity of 72%(95%CI:63.3-79.3).We conclude that the prevalence of EBV infection is low in the healthy population in this region and that a high EBV load at baseline is more common in LT,IM,and Lymphocyte Leukemia(LL).Conclusion This study used a large-sample survey to characterize the prevalence of whole-blood EBV levels in various diseases,including the stages and subtypes.The EBV detection rate was higher in patients with malignant disease than in those with benign disease.Our study provides clinicians with baseline information regarding EBV-associated diseases.展开更多
Soybean mosaic virus(SMV),an RNA virus,is the most common and destructive pathogenic virus in soybean fields.The newly developed CRISPR/Cas immune system has provided a novel strategy for improving plant resistance to...Soybean mosaic virus(SMV),an RNA virus,is the most common and destructive pathogenic virus in soybean fields.The newly developed CRISPR/Cas immune system has provided a novel strategy for improving plant resistance to viruses;hence,this study aimed to engineer SMV resistance in soybean using this system.Specifically,multiple sgRNAs were designed to target positive-and/or negative-sense strands of the SMV HC-Pro gene.Subsequently,the corresponding CRISPR/CasRx vectors were constructed and transformed into soybeans.After inoculation with SMV,39.02%,35.77%,and 18.70%of T_(1)plants were confirmed to be highly resistant(HR),resistant(R),and mildly resistant(MR)to SMV,respectively,whereas only 6.50%were identified as susceptible(S).Additionally,qRT-PCR and DAS-ELISA showed that,both at 15 and 30 d post-inoculation(dpi),SMV accumulation significantly decreased or was even undetectable in HR and R plants,followed by MR and S plants.Additionally,the expression level of the CasRx gene varied in almost all T_(1)plants with different resistance level,both at 15 and 30 dpi.Furthermore,when SMV resistance was evaluated in the T_(2)generation,the results were similar to those recorded for the T_(1)generation.These findings provide new insights into the application of the CRISPR/CasRx system for soybean improvement and offer a promising alternative strategy for breeding for resistance to biotic stress that will contribute to the development of SMV-immune soybean germplasm to accelerate progress towards greater soybean crop productivity.展开更多
Nipah virus (NiV) is a highly infectious zoonotic pathogen that poses a significant threat to human and animal health. First identified in Malaysia in 1998, NiV has since caused several outbreaks in Southeast Asia, wi...Nipah virus (NiV) is a highly infectious zoonotic pathogen that poses a significant threat to human and animal health. First identified in Malaysia in 1998, NiV has since caused several outbreaks in Southeast Asia, with sporadic cases reported in Bangladesh and India. The virus is primarily transmitted to humans through direct contact with infected animals, primarily fruit bats, or through the consumption of contaminated fruits and their juices. NiV infection presents a wide spectrum of clinical features, ranging from mild respiratory illness to severe encephalitis, with a high case fatality rate. The incubation period typically ranges from 4 to 14 days, during which patients develop fever, headache, myalgia, and respiratory symptoms such as cough and sore throat. As the disease progresses, neurological signs become prominent, including altered consciousness, seizures, and focal deficits. Severe cases may exhibit acute respiratory distress syndrome and multi organ failure. Laboratory findings often include lymphocytopenia, thrombocytopenia, and elevated liver enzymes. Diagnosis of NiV infection requires specialized laboratory testing, including reverse transcription-polymerase chain reaction (RT-PCR) and serological assays. Currently, no specific antiviral treatment exists for NiV infection, and management primarily focuses on supportive care. Prevention and control strategies encompass public health interventions, surveillance, and raising awareness among healthcare providers and the general population. The emergence and re-emergence of NiV highlight the urgent need for continued research, improved diagnostic capabilities, and the development of effective vaccines and therapeutics to mitigate the impact of this deadly virus.展开更多
According to the report from the Chinese Center for Disease Control and Prevention,the prevalence of human immunodeficiency virus(HIV)infection exceeded 1.2 million individuals by the year 2022,with an annual increase...According to the report from the Chinese Center for Disease Control and Prevention,the prevalence of human immunodeficiency virus(HIV)infection exceeded 1.2 million individuals by the year 2022,with an annual increase of about 80000 cases.The overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%,almost twice the rate of the general population in China.In addition to the well-documented susceptibility to opportunistic infections and new malignancies,HIV infected patients frequently experience liver-related organ damage,with the liver and kidneys being the most commonly affected.This often leads to the development of end-stage liver and kidney diseases.Therefore,organ transplantation has emerged as an important part of active treatment for HIV infected patients.However,the curative effect is not satisfactory.HIV infection has been considered a contraindication for organ transplantation.Until the emergence of highly active anti-retroviral therapy in 1996,the once intractable replication of retrovirus was effectively inhibited.With prolonged survival,the failure of important organs has become the main cause of death among HIV patients.Therefore,transplant centers worldwide have resu-med exploration of organ transplantation for HIV-infected individuals and reached a positive conclusion.This study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation(LT)in main-land China.To date,our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV,and all but one,who died two months postoperatively due to sepsis and progressive multi-organ failure,have survived.Comparative analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions,cytomegalovirus infection,bacteremia,pulmonary infections,acute kidney injury,new-onset cancers,or vascular and biliary complications.展开更多
Objective: Describe the epidemiological and paraclinical aspects of HP infection in hepatitis B virus carriers. Population and Method: This was a descriptive cross-sectional study running from January 1 to August 30, ...Objective: Describe the epidemiological and paraclinical aspects of HP infection in hepatitis B virus carriers. Population and Method: This was a descriptive cross-sectional study running from January 1 to August 30, 2019, a period of 8 months. It took place in the Hospital Centers of the two major cities of Congo (Brazzaville and Pointe-Noire). The target population of our study consists of patients carrying HBV under antiviral treatment or not. Patients aged at least 18 years and consenting with a biological and morphological assessment were included. We did not include in our study patients taking or having taken antibiotics and/or PPIs less than 4 weeks ago. We excluded all patients who did not deposit fresh stools and those in whom stool extraction could not be done manually. The variables studied covered sociodemographic, clinical and paraclinical aspects. Data entry was done using Excel 8.0 software. Statistical analysis was carried out with SPSS 20.0 software. Results: During our study, we included 169 patients. The frequency of HPAG in the stools of HBV carriers in our study population was 63.9% (n = 109). Male patients represented 69% (n = 75) and female patients represented 31% (n = 34). The average age of the patients is 43.92 ± 13.51 years with extremes of 18 years and 80 years. Concerning profession, unemployed patients and those working in the private sector were the most represented in respectively 28.4% (n = 31) and 22.9% (n = 25) without statistical link. Households comprising between 4 - 10 people and the use of public latrines were the risk factors most represented in respectively 69% (n = 75) and 88% (n = 96) without statistical link. Clinically, hepatomegaly and signs of portal hypertension were most represented in 53% (n = 58) and 47% (n = 51). Biologically, HBV DNA was detectable in 60.5% of cases (n = 66).展开更多
The small and scattered enterprise pattern in the county economy has formed numerous sporadic pollution sources, hindering the centralized treatment of the water environment, increasing the cost and difficulty of trea...The small and scattered enterprise pattern in the county economy has formed numerous sporadic pollution sources, hindering the centralized treatment of the water environment, increasing the cost and difficulty of treatment. How enterprises can make reasonable decisions on their water environment behavior based on the external environment and their own factors is of great significance for scientifically and effectively designing water environment regulation mechanisms. Based on optimal control theory, this study investigates the design of contractual mechanisms for water environmental regulation for small and medium-sized enterprises. The enterprise is regarded as an independent economic entity that can adopt optimal control strategies to maximize its own interests. Based on the participation of multiple subjects including the government, enterprises, and the public, an optimal control strategy model for enterprises under contractual water environmental regulation is constructed using optimal control theory, and a method for calculating the amount of unit pollutant penalties is derived. The water pollutant treatment cost data of a paper company is selected to conduct empirical numerical analysis on the model. The results show that the increase in the probability of government regulation and public participation, as well as the decrease in local government protection for enterprises, can achieve the same regulatory effect while reducing the number of administrative penalties per unit. Finally, the implementation process of contractual water environmental regulation for small and medium-sized enterprises is designed.展开更多
In this editorial we comment on the article published in the recent issue of the W orld Journal of Gastroenterology.We focus specifically on the problem of occult hepatitis B virus(HBV)infection,that is a result of pr...In this editorial we comment on the article published in the recent issue of the W orld Journal of Gastroenterology.We focus specifically on the problem of occult hepatitis B virus(HBV)infection,that is a result of previous hepatitis B(PHB)and a source for reactivation of HBV.The prevalence of PHB is underestimated due to the lack of population testing programs.However,this condition not only com-plicate anticancer treatment,but may be responsible for the development of other diseases,like cancer or autoimmune disorders.Here we unveil possible mecha-nisms responsible for realization of these processes and suggest practical approa-ches for diagnosis and treatment.展开更多
Enterprise risk management holds significant importance in fostering sustainable growth of businesses and in serving as a critical element for regulatory bodies to uphold market order.Amidst the challenges posed by in...Enterprise risk management holds significant importance in fostering sustainable growth of businesses and in serving as a critical element for regulatory bodies to uphold market order.Amidst the challenges posed by intricate and unpredictable risk factors,knowledge graph technology is effectively driving risk management,leveraging its ability to associate and infer knowledge from diverse sources.This review aims to comprehensively summarize the construction techniques of enterprise risk knowledge graphs and their prominent applications across various business scenarios.Firstly,employing bibliometric methods,the aim is to uncover the developmental trends and current research hotspots within the domain of enterprise risk knowledge graphs.In the succeeding section,systematically delineate the technical methods for knowledge extraction and fusion in the standardized construction process of enterprise risk knowledge graphs.Objectively comparing and summarizing the strengths and weaknesses of each method,we provide recommendations for addressing the existing challenges in the construction process.Subsequently,categorizing the applied research of enterprise risk knowledge graphs based on research hotspots and risk category standards,and furnishing a detailed exposition on the applicability of technical routes and methods.Finally,the future research directions that still need to be explored in enterprise risk knowledge graphs were discussed,and relevant improvement suggestions were proposed.Practitioners and researchers can gain insights into the construction of technical theories and practical guidance of enterprise risk knowledge graphs based on this foundation.展开更多
As the realm of enterprise-level conversational AI continues to evolve, it becomes evident that while generalized Large Language Models (LLMs) like GPT-3.5 bring remarkable capabilities, they also bring forth formidab...As the realm of enterprise-level conversational AI continues to evolve, it becomes evident that while generalized Large Language Models (LLMs) like GPT-3.5 bring remarkable capabilities, they also bring forth formidable challenges. These models, honed on vast and diverse datasets, have undoubtedly pushed the boundaries of natural language understanding and generation. However, they often stumble when faced with the intricate demands of nuanced enterprise applications. This research advocates for a strategic paradigm shift, urging enterprises to embrace a fine-tuning approach as a means to optimize conversational AI. While generalized LLMs are linguistic marvels, their inability to cater to the specific needs of businesses across various industries poses a critical challenge. This strategic shift involves empowering enterprises to seamlessly integrate their own datasets into LLMs, a process that extends beyond linguistic enhancement. The core concept of this approach centers on customization, enabling businesses to fine-tune the AI’s functionality to fit precisely within their unique business landscapes. By immersing the LLM in industry-specific documents, customer interaction records, internal reports, and regulatory guidelines, the AI transcends its generic capabilities to become a sophisticated conversational partner aligned with the intricacies of the enterprise’s domain. The transformative potential of this fine-tuning approach cannot be overstated. It enables a transition from a universal AI solution to a highly customizable tool. The AI evolves from being a linguistic powerhouse to a contextually aware, industry-savvy assistant. As a result, it not only responds with linguistic accuracy but also with depth, relevance, and resonance, significantly elevating user experiences and operational efficiency. In the subsequent sections, this paper delves into the intricacies of fine-tuning, exploring the multifaceted challenges and abundant opportunities it presents. It addresses the technical intricacies of data integration, ethical considerations surrounding data usage, and the broader implications for the future of enterprise AI. The journey embarked upon in this research holds the potential to redefine the role of conversational AI in enterprises, ushering in an era where AI becomes a dynamic, deeply relevant, and highly effective tool, empowering businesses to excel in an ever-evolving digital landscape.展开更多
基金supported by UniversitàCattolica(D1 intramural funds to RP)Italian Ministry of University and Research(PRIN 2022ZYLB7B,P2022YW7BP funds to CG).
文摘Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.
文摘The outbreak of novel coronavirus pneumonia has affected almost all industries and enterprises.This paper analyzes the impact of the epidemic on the macro economy through GDP and other indicators,analyzes the impact of the epidemic on the overall business performance of the enterprises through the asset turnover speed index of the above scale industrial enterprises,and analyzes the impact of the epidemic on the net profit of the listed companies through the first quarter performance forecast of the listed companies.At last,the paper puts forward that enterprises should improve their awareness and ability to resist risks.
文摘BACKGROUND Gut microbiota(GM)affects the progression and response to treatment in liver diseases.The GM composition is diverse and associated with different etiologies of liver diseases.Notably,alterations in GM alterations are observed in patients with portal hypertension(PH)secondary to cirrhosis,with hepatitis B virus(HBV)infection being a major cause of cirrhosis in China.Thus,understanding the role of GM alterations in patients with HBV infection-related PH is essential.AIM To evaluate GM alterations in patients with HBV-related PH after transjugular intrahepatic portosystemic shunt(TIPS)placement.METHODS This was a prospective,observational clinical study.There were 30 patients(with a 100%technical success rate)recruited in the present study.Patients with esophagogastric variceal bleeding due to HBV infection-associated PH who underwent TIPS were enrolled.Stool samples were obtained before and one month after TIPS treatment,and GM was analyzed using 16S ribosomal RNA amplicon sequencing.RESULTS One month after TIPS placement,8 patients developed hepatic encephalopathy(HE)and were assigned to the HE group;the other 22 patients were assigned to the non-HE group.There was no substantial disparity in the abundance of GM at the phylum level between the two groups,regardless of TIPS treatment(all,P>0.05).However,following TIPS placement,the following results were observed:(1)The abundance of Haemophilus and Eggerthella increased,whereas that of Anaerostipes,Dialister,Butyricicoccus,and Oscillospira declined in the HE group;(2)The richness of Eggerthella,Streptococcus,and Bilophila increased,whereas that of Roseburia and Ruminococcus decreased in the non-HE group;and(3)Members from the pathogenic genus Morganella appeared in the HE group but not in the non-HE group.CONCLUSION Intestinal microbiota-related synergism may predict the risk of HE following TIPS placement in patients with HBVrelated PH.Prophylactic microbiome therapies may be useful for preventing and treating HE after TIPS placement.
文摘BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.
文摘Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.
基金This work is supported by the United Arab Emirates University UPAR(Grant No.G3458).
文摘Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the scientific community.Numerous trials have been conducted to develop treatment options for ZIKV infection.This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection.A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development.The results indicate that several therapeutic interventions are being tested against ZIKV infection,such as DNA vaccines,subunit vaccines,live-attenuated vaccines,virus-vector-based vaccines,inactivated vaccines,virus-like particles,and mRNA-based vaccines.In addition,approved anti-ZIKV drugs that can reduce the global burden are discussed.Although many vaccine candidates for ZIKV are at different stages of development,none of them have received Food and Drug Authority approval for use up to now.The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.
基金Supported by National Natural Science Foundation of China,No.82070649.
文摘BACKGROUND Although the benefits of antiviral therapy for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)have been proven,researchers have not con-firmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time(at least 24 wk)and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC.AIM To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC.METHODS A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi’an Jiaotong University from January 2016 to June 2019 was conducted.Considering the history of antiviral therapy,patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups.RESULTS Kaplan–Meier analysis revealed significant differences in overall survival(P<0.0001)and disease-free survival(P=0.035)between the two groups.Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival(hazard ratio=0.27;95%confidence interval:0.08-0.88;P=0.030).CONCLUSION In patients with HBV-related HCC,it is ideal to receive preoperative long-term antiviral therapy,which helps patients tolerate more extensive hepatectomy;however,remedial antiviral therapy,which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL,can also result in improved outcomes.
文摘BACKGROUND Chronic hepatitis C virus(HCV)infection is a major global health concern that leads to liver fibrosis,cirrhosis,and cancer.Regimens containing direct-acting antivirals(DAAs)have become the mainstay of HCV treatment,achieving a high sustained virological response(SVR)with minimal adverse events.CASE SUMMARY A 74-year-old woman with chronic HCV infection was treated with the DAAs ledipasvir,and sofosbuvir for 12 wk and achieved SVR.Twenty-four weeks after treatment completion,the liver enzyme and serum IgG levels increased,and antinuclear antibody became positive without HCV viremia,suggesting the development of autoimmune hepatitis(AIH).After liver biopsy indicated AIH,a definite AIH diagnosis was made and prednisolone was initiated.The treatment was effective,and the liver enzyme and serum IgG levels normalized.However,multiple strictures of the intrahepatic and extrahepatic bile ducts with dilatation of the peripheral bile ducts appeared on magnetic resonance cholangiopancreatography after 3 years of achieving SVR,which were consistent with primary sclerosing cholangitis.CONCLUSION The potential risk of developing autoimmune liver diseases after DAA treatment should be considered.
基金sponsored by Hangzhou Medical Health Science and Technology Project[No.A20220558]the Special Supporting Program of Agriculture and Social Development from Hangzhou Municipal Science&Technology Bureau[No.202203B34].
文摘Objective This study aimed to investigate the prevalence of Epstein-Barr virus(EBV)infection in patients with and without cancer.Methods A total of 26,648 participants who underwent whole-blood EBV DNA(WBEBV)assays between January 1,2020,and August 31,2023,were included.The chi-square test was used for categorical data analysis,and R software was used to analyze the differences in EBV DNA load levels and the diagnostic capabilities of WBEBV.Results Positive rates were 10.2%and 25.4%for healthy controls(HC)and patients,respectively.The positivity rate for EBV-associated neoplasms(EN)was the highest at 7.53%,followed by leukemia(Le)at 5.49%.The subgroup analysis showed that the positivity rate for abnormal proliferation or hyperplasia(APH)was 31.9%,followed by 30.5%for Le.The WBEBV of patients with transplants(TP),especially living-related transplants(LT),was the highest among all subgroups.WBEBV at diagnosis was used to differentiate between infectious mononucleosis(IM)and chronic active Epstein-Barr virus(CAEBV),with a sensitivity of 67.4%(95%confidence interval[CI]:57.6-75.8)and specificity of 72%(95%CI:63.3-79.3).We conclude that the prevalence of EBV infection is low in the healthy population in this region and that a high EBV load at baseline is more common in LT,IM,and Lymphocyte Leukemia(LL).Conclusion This study used a large-sample survey to characterize the prevalence of whole-blood EBV levels in various diseases,including the stages and subtypes.The EBV detection rate was higher in patients with malignant disease than in those with benign disease.Our study provides clinicians with baseline information regarding EBV-associated diseases.
基金supported by grants from National Natural Science Foundation of China(32001571)R&D Program of Beijing Municipal Education Commission(KM202212448003,KM202312448004)+4 种基金Science and Technology Innovation Project of Beijing Vocational College of Agriculture(XY-YF-22-02)Zhongshan Biological Breeding Laboratory(ZSBBL-KY2023-03)China Agriculture Research System of MOF and MARA(CARS-04)Jiangsu Collaborative Innovation Center for Modern Crop Production(JCICMCP)Collaborative Innovation Center for Modern Crop Production co-sponsored by Province and Ministry(CIC-MCP).
文摘Soybean mosaic virus(SMV),an RNA virus,is the most common and destructive pathogenic virus in soybean fields.The newly developed CRISPR/Cas immune system has provided a novel strategy for improving plant resistance to viruses;hence,this study aimed to engineer SMV resistance in soybean using this system.Specifically,multiple sgRNAs were designed to target positive-and/or negative-sense strands of the SMV HC-Pro gene.Subsequently,the corresponding CRISPR/CasRx vectors were constructed and transformed into soybeans.After inoculation with SMV,39.02%,35.77%,and 18.70%of T_(1)plants were confirmed to be highly resistant(HR),resistant(R),and mildly resistant(MR)to SMV,respectively,whereas only 6.50%were identified as susceptible(S).Additionally,qRT-PCR and DAS-ELISA showed that,both at 15 and 30 d post-inoculation(dpi),SMV accumulation significantly decreased or was even undetectable in HR and R plants,followed by MR and S plants.Additionally,the expression level of the CasRx gene varied in almost all T_(1)plants with different resistance level,both at 15 and 30 dpi.Furthermore,when SMV resistance was evaluated in the T_(2)generation,the results were similar to those recorded for the T_(1)generation.These findings provide new insights into the application of the CRISPR/CasRx system for soybean improvement and offer a promising alternative strategy for breeding for resistance to biotic stress that will contribute to the development of SMV-immune soybean germplasm to accelerate progress towards greater soybean crop productivity.
文摘Nipah virus (NiV) is a highly infectious zoonotic pathogen that poses a significant threat to human and animal health. First identified in Malaysia in 1998, NiV has since caused several outbreaks in Southeast Asia, with sporadic cases reported in Bangladesh and India. The virus is primarily transmitted to humans through direct contact with infected animals, primarily fruit bats, or through the consumption of contaminated fruits and their juices. NiV infection presents a wide spectrum of clinical features, ranging from mild respiratory illness to severe encephalitis, with a high case fatality rate. The incubation period typically ranges from 4 to 14 days, during which patients develop fever, headache, myalgia, and respiratory symptoms such as cough and sore throat. As the disease progresses, neurological signs become prominent, including altered consciousness, seizures, and focal deficits. Severe cases may exhibit acute respiratory distress syndrome and multi organ failure. Laboratory findings often include lymphocytopenia, thrombocytopenia, and elevated liver enzymes. Diagnosis of NiV infection requires specialized laboratory testing, including reverse transcription-polymerase chain reaction (RT-PCR) and serological assays. Currently, no specific antiviral treatment exists for NiV infection, and management primarily focuses on supportive care. Prevention and control strategies encompass public health interventions, surveillance, and raising awareness among healthcare providers and the general population. The emergence and re-emergence of NiV highlight the urgent need for continued research, improved diagnostic capabilities, and the development of effective vaccines and therapeutics to mitigate the impact of this deadly virus.
基金Supported by the Shenzhen Science and Technology R&D Fund,No.JCYJ20220530163011026Shenzhen Third People’s Hospital,No.G2022008 and No.G2021008.
文摘According to the report from the Chinese Center for Disease Control and Prevention,the prevalence of human immunodeficiency virus(HIV)infection exceeded 1.2 million individuals by the year 2022,with an annual increase of about 80000 cases.The overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%,almost twice the rate of the general population in China.In addition to the well-documented susceptibility to opportunistic infections and new malignancies,HIV infected patients frequently experience liver-related organ damage,with the liver and kidneys being the most commonly affected.This often leads to the development of end-stage liver and kidney diseases.Therefore,organ transplantation has emerged as an important part of active treatment for HIV infected patients.However,the curative effect is not satisfactory.HIV infection has been considered a contraindication for organ transplantation.Until the emergence of highly active anti-retroviral therapy in 1996,the once intractable replication of retrovirus was effectively inhibited.With prolonged survival,the failure of important organs has become the main cause of death among HIV patients.Therefore,transplant centers worldwide have resu-med exploration of organ transplantation for HIV-infected individuals and reached a positive conclusion.This study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation(LT)in main-land China.To date,our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV,and all but one,who died two months postoperatively due to sepsis and progressive multi-organ failure,have survived.Comparative analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions,cytomegalovirus infection,bacteremia,pulmonary infections,acute kidney injury,new-onset cancers,or vascular and biliary complications.
文摘Objective: Describe the epidemiological and paraclinical aspects of HP infection in hepatitis B virus carriers. Population and Method: This was a descriptive cross-sectional study running from January 1 to August 30, 2019, a period of 8 months. It took place in the Hospital Centers of the two major cities of Congo (Brazzaville and Pointe-Noire). The target population of our study consists of patients carrying HBV under antiviral treatment or not. Patients aged at least 18 years and consenting with a biological and morphological assessment were included. We did not include in our study patients taking or having taken antibiotics and/or PPIs less than 4 weeks ago. We excluded all patients who did not deposit fresh stools and those in whom stool extraction could not be done manually. The variables studied covered sociodemographic, clinical and paraclinical aspects. Data entry was done using Excel 8.0 software. Statistical analysis was carried out with SPSS 20.0 software. Results: During our study, we included 169 patients. The frequency of HPAG in the stools of HBV carriers in our study population was 63.9% (n = 109). Male patients represented 69% (n = 75) and female patients represented 31% (n = 34). The average age of the patients is 43.92 ± 13.51 years with extremes of 18 years and 80 years. Concerning profession, unemployed patients and those working in the private sector were the most represented in respectively 28.4% (n = 31) and 22.9% (n = 25) without statistical link. Households comprising between 4 - 10 people and the use of public latrines were the risk factors most represented in respectively 69% (n = 75) and 88% (n = 96) without statistical link. Clinically, hepatomegaly and signs of portal hypertension were most represented in 53% (n = 58) and 47% (n = 51). Biologically, HBV DNA was detectable in 60.5% of cases (n = 66).
文摘The small and scattered enterprise pattern in the county economy has formed numerous sporadic pollution sources, hindering the centralized treatment of the water environment, increasing the cost and difficulty of treatment. How enterprises can make reasonable decisions on their water environment behavior based on the external environment and their own factors is of great significance for scientifically and effectively designing water environment regulation mechanisms. Based on optimal control theory, this study investigates the design of contractual mechanisms for water environmental regulation for small and medium-sized enterprises. The enterprise is regarded as an independent economic entity that can adopt optimal control strategies to maximize its own interests. Based on the participation of multiple subjects including the government, enterprises, and the public, an optimal control strategy model for enterprises under contractual water environmental regulation is constructed using optimal control theory, and a method for calculating the amount of unit pollutant penalties is derived. The water pollutant treatment cost data of a paper company is selected to conduct empirical numerical analysis on the model. The results show that the increase in the probability of government regulation and public participation, as well as the decrease in local government protection for enterprises, can achieve the same regulatory effect while reducing the number of administrative penalties per unit. Finally, the implementation process of contractual water environmental regulation for small and medium-sized enterprises is designed.
基金Supported by Ministry of Science and Higher education of Russia,No.FGMF-2022-0005Moscow Healthcare Department,No.123040700014-4.
文摘In this editorial we comment on the article published in the recent issue of the W orld Journal of Gastroenterology.We focus specifically on the problem of occult hepatitis B virus(HBV)infection,that is a result of previous hepatitis B(PHB)and a source for reactivation of HBV.The prevalence of PHB is underestimated due to the lack of population testing programs.However,this condition not only com-plicate anticancer treatment,but may be responsible for the development of other diseases,like cancer or autoimmune disorders.Here we unveil possible mecha-nisms responsible for realization of these processes and suggest practical approa-ches for diagnosis and treatment.
基金supported by the Shandong Province Science and Technology Project(2023TSGC0509,2022TSGC2234)Qingdao Science and Technology Plan Project(23-1-5-yqpy-2-qy).
文摘Enterprise risk management holds significant importance in fostering sustainable growth of businesses and in serving as a critical element for regulatory bodies to uphold market order.Amidst the challenges posed by intricate and unpredictable risk factors,knowledge graph technology is effectively driving risk management,leveraging its ability to associate and infer knowledge from diverse sources.This review aims to comprehensively summarize the construction techniques of enterprise risk knowledge graphs and their prominent applications across various business scenarios.Firstly,employing bibliometric methods,the aim is to uncover the developmental trends and current research hotspots within the domain of enterprise risk knowledge graphs.In the succeeding section,systematically delineate the technical methods for knowledge extraction and fusion in the standardized construction process of enterprise risk knowledge graphs.Objectively comparing and summarizing the strengths and weaknesses of each method,we provide recommendations for addressing the existing challenges in the construction process.Subsequently,categorizing the applied research of enterprise risk knowledge graphs based on research hotspots and risk category standards,and furnishing a detailed exposition on the applicability of technical routes and methods.Finally,the future research directions that still need to be explored in enterprise risk knowledge graphs were discussed,and relevant improvement suggestions were proposed.Practitioners and researchers can gain insights into the construction of technical theories and practical guidance of enterprise risk knowledge graphs based on this foundation.
文摘As the realm of enterprise-level conversational AI continues to evolve, it becomes evident that while generalized Large Language Models (LLMs) like GPT-3.5 bring remarkable capabilities, they also bring forth formidable challenges. These models, honed on vast and diverse datasets, have undoubtedly pushed the boundaries of natural language understanding and generation. However, they often stumble when faced with the intricate demands of nuanced enterprise applications. This research advocates for a strategic paradigm shift, urging enterprises to embrace a fine-tuning approach as a means to optimize conversational AI. While generalized LLMs are linguistic marvels, their inability to cater to the specific needs of businesses across various industries poses a critical challenge. This strategic shift involves empowering enterprises to seamlessly integrate their own datasets into LLMs, a process that extends beyond linguistic enhancement. The core concept of this approach centers on customization, enabling businesses to fine-tune the AI’s functionality to fit precisely within their unique business landscapes. By immersing the LLM in industry-specific documents, customer interaction records, internal reports, and regulatory guidelines, the AI transcends its generic capabilities to become a sophisticated conversational partner aligned with the intricacies of the enterprise’s domain. The transformative potential of this fine-tuning approach cannot be overstated. It enables a transition from a universal AI solution to a highly customizable tool. The AI evolves from being a linguistic powerhouse to a contextually aware, industry-savvy assistant. As a result, it not only responds with linguistic accuracy but also with depth, relevance, and resonance, significantly elevating user experiences and operational efficiency. In the subsequent sections, this paper delves into the intricacies of fine-tuning, exploring the multifaceted challenges and abundant opportunities it presents. It addresses the technical intricacies of data integration, ethical considerations surrounding data usage, and the broader implications for the future of enterprise AI. The journey embarked upon in this research holds the potential to redefine the role of conversational AI in enterprises, ushering in an era where AI becomes a dynamic, deeply relevant, and highly effective tool, empowering businesses to excel in an ever-evolving digital landscape.