BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemis...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.展开更多
BACKGROUND Massive hemorrhagic ascites caused by endometriosis is exceedingly rare,and the treatment strategy remains controversial.Here,we report a case of endometriosis with massive hemorrhagic ascites treated with ...BACKGROUND Massive hemorrhagic ascites caused by endometriosis is exceedingly rare,and the treatment strategy remains controversial.Here,we report a case of endometriosis with massive hemorrhagic ascites treated with a novel triple therapy including conservative surgery,gonadotropin-releasing hormone agonist,and then dienogest.CASE SUMMARY A 28-year-old nulliparous patient was admitted to Shengjing Hospital of China Medical University,and exploratory laparoscopy was performed.A total of 9500 mL of brown ascites was aspirated from the pelvic cavity,the bilateral ovaries strongly adhered to the posterior of the uterus and were fixed to the pelvic floor,and endometriotic cysts were not observed in either ovary.The pelvic and abdominal peritonea were covered with patchy red,white,and brown endometriotic lesions and defects.Partial surgical resection of endometriotic lesions on the peritoneum was performed while we simultaneously collected multiple peritoneal biopsies.The final pathological diagnosis was endometriosis coupled with hemorrhagic necrotic tissue.CONCLUSION Postoperative injection of gonadotropin-releasing hormone agonist was provided three times,followed by dienogest administration,and we will continue to follow up with this ongoing treatment.展开更多
Ameloblastoma is a benign but locally aggressive odontogenic neoplasm that accounts for 10% of all tumors arising in the mandible and maxilla (1). Eighty percent of ameloblastomas arise in the mandible, and they are u...Ameloblastoma is a benign but locally aggressive odontogenic neoplasm that accounts for 10% of all tumors arising in the mandible and maxilla (1). Eighty percent of ameloblastomas arise in the mandible, and they are usually found in young adults. It frequently recurs if not adequately展开更多
BACKGROUND The 2020 European Association of Urology prostate cancer guidelines recommend androgen deprivation therapy(ADT)in combination with apalutamide and enzalutamide,a new generation of androgen receptor antagoni...BACKGROUND The 2020 European Association of Urology prostate cancer guidelines recommend androgen deprivation therapy(ADT)in combination with apalutamide and enzalutamide,a new generation of androgen receptor antagonists,as first-line therapy.A decrease in prostate-specific antigen(PSA)levels may occur in the early stages of novel hormonal therapy;however,radionuclide bone imaging may suggest disease progression.During follow-up,PSA,radionuclide bone imaging,and prostate-specific membrane antigen(PSMA)positron emission tomography–computed tomography(PET-CT)are needed for systematic evaluation.CASE SUMMARY We admitted a 56-year-old male patient with metastatic hormone-sensitive prostate cancer.Initial radionuclide bone imaging,magnetic resonance imaging(MRI),and PSMA PET-CT showed prostate cancer with multiple bone metastases.Ultrasound-guided needle biopsy of the prostate revealed a poorly differentiated adenocarcinoma of the prostate with a Gleason score:5+4=9.The final diagnosis was a prostate adenocarcinoma(T4N1M1).ADT with novel hormonal therapy(goseraline sustained-release implant 3.6 mg monthly and apalutamide 240 mg daily)was commenced.Three months later,radionuclide bone imaging and MRI revealed advanced bone metastasis.However,PSMA PET-CT examination showed a significant reduction in PSMA aggregation on the bone,indicating improved bone metastases.Considering that progressive decrease in the presenting lumbar pain,treatment strategies were considered to be effective.CONCLUSION ADT using novel hormonal therapy is effective for treating patients with prostate adenocarcinoma.Careful evaluation must precede treatment plan changes.展开更多
Gastric cancer(GC) is a common lethal malignancy.Gastroesophageal junction and gastric cardia tumors are the fastest rising malignancies due to increasing prevalence of obesity and acid reflex in the United States.Tra...Gastric cancer(GC) is a common lethal malignancy.Gastroesophageal junction and gastric cardia tumors are the fastest rising malignancies due to increasing prevalence of obesity and acid reflex in the United States.Traditional chemotherapy remains the main treatment with trastuzumab targeting human epidermal growth factor receptor 2 positive disease.The median overall survival(OS) is less than one year for advanced GC patients; thus,there is an urgent unmet need to develop novel therapy for GC.Although multiple targeted agents were studied,only the vascular endothelial growth factor receptor inhibitor ramucirumab was approved recently by the United States Food and Drug Administration because of its 1.4 mo OS benefit(5.2 mo vs 3.8 mo,P = 0.047) as a single agent; 2.2 mo improvement of survival(9.6 mo vs 7.4 mo,P = 0.017) when combined with paclitaxel in previously treated advanced GC patients.It is the first single agent approved for previously treated GC and the second biologic agent after trastuzumab.Even with limited success,targeted therapy may be improved by developing new biomarkers.Immune therapy is changing the paradigm of cancer treatment and is presently under active investigation for GC in clinical trials.More evidence supports GC stem cells existence and early stage studies are looking for its potential therapeutic possibilities.展开更多
Schwann cells are the myelinating glial cells of the peripheral nervous system（PNS）.By establishing lipid-rich myelin sheaths around large-caliber axons,they ensure that electrical signal transmission is accelerated...Schwann cells are the myelinating glial cells of the peripheral nervous system（PNS）.By establishing lipid-rich myelin sheaths around large-caliber axons,they ensure that electrical signal transmission is accelerated-a process referred to as saltatory signal propagation.Apart from this prominent physiological function,these cells also exert important pathophysiological roles in PNS injuries or dis- eases. In contrast to the central nervous system （CNS）, the adult PNS retains a remarkably high degree of intrinsic re- generation. As a consequence, transected axons and dam- aged myelin sheaths can be repaired and nerve functional- ity can be restored. This spontaneous regenerative capacity depends on （inter） actions of macrophages, neurons, and Schwann cells.展开更多
Heart failure with reduced ejection fraction(HFrEF)and nonalcoholic fatty liver disease(NAFLD)are two common comorbidities that share similar pathophysiological mechanisms.There is a growing interest in the potential ...Heart failure with reduced ejection fraction(HFrEF)and nonalcoholic fatty liver disease(NAFLD)are two common comorbidities that share similar pathophysiological mechanisms.There is a growing interest in the potential of targeted therapies to improve outcomes in patients with coexisting HFrEF and NAFLD.This manuscript reviews current and potential therapies for patients with coexisting HFrEF and NAFLD.Pharmacological therapies,including angiotensinconverting enzyme inhibitors/angiotensin receptor blockers,mineralocorticoids receptor antagonist,and sodium-glucose cotransporter-2 inhibitors,have been shown to reduce fibrosis and fat deposits in the liver.However,there are currently no data showing the beneficial effects of sacubitril/valsartan,ivabradine,hydralazine,isosorbide nitrates,digoxin,or beta blockers on NAFLD in patients with HFrEF.This study highlights the importance of considering HFrEF and NAFLD when developing treatment plans for patients with these comorbidities.Further research is needed in patients with coexisting HFrEF and NAFLD,with an emphasis on novel therapies and the importance of a multidisciplinary approach for managing these complex comorbidities.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
Chronic hepatitis B constitutes a substantial disease burden worldwide.The steps advocated by the World Health Organization in 2016 to eradicate hepatitis B by 2030 has failed to achieve significant progress,especiall...Chronic hepatitis B constitutes a substantial disease burden worldwide.The steps advocated by the World Health Organization in 2016 to eradicate hepatitis B by 2030 has failed to achieve significant progress,especially with respect to immu-nization coverage and linkage to care.The lack of governmental and public awar-eness regarding the long-term implications of hepatitis B burden cause under-funding of developmental projects.The presently approved treatment modalities have limited efficacy in complete viral eradication,hence the need for newer molecules to achieve functional cure(sustained undetectable hepatitis B surface antigen(HBsAg)and hepatitis B virus DNA in peripheral blood after a finite period of therapy).However,preliminary results from trials of novel therapies show their inadequacy to achieve this end by themselves but better performance with a low baseline serum HBsAg with nucleos(t)ide analogues(NA)treatment which need to be combined with/without pegylated interferon as an immu-nomodulator.Such therapy is limited by cost and adverse events and need to show incremental benefit over the standard of care(long-term NA therapy)with respect to efficacy and drug toxicities,making the development process tenuous.Thus,while such therapies continue to be tested,strategies should still focus on prevention of transmission by non-pharmaceutical measures,vaccination and increasing linkage to care.展开更多
Autoimmune hepatitis is an uncommon condition that affects both adults and children and is characterized by chronic and recurrent inflammatory activity in the liver.This inflammation is accompanied by elevated IgG and...Autoimmune hepatitis is an uncommon condition that affects both adults and children and is characterized by chronic and recurrent inflammatory activity in the liver.This inflammation is accompanied by elevated IgG and autoantibody levels.Historically,treatment consists of steroids with the addition of azathioprine,which results in remission in approximately 80%of patients.Despite significant advancements in our understanding of the immune system over the past two decades,few modifications have been made to treatment algorithms,which have remained largely unchanged since they were first proposed more than 40 years ago.This review summarized the various treatment options currently available as well as our experiences using them.Although steroids are the standard treatment for induction therapy,other medications may be considered.Cyclosporin A,a calcineurin inhibitor that decreases T cell activation,has proven effective for induction of remission,but its long-term side effects limit its appeal for maintenance.Tacrolimus,a drug belonging to the same family,has been used in patients with refractory diseases with fewer side effects.Sirolimus and everolimus have interesting effects on regulatory T cell populations and may become viable options in the future.Mycophenolate mofetil is not effective for induction but is a valid alternative for patients who are intolerant to azathioprine.B celldepleting drugs,such as rituximab and belimumab,have been successfully used in refractory cases and are useful in both the short and long term.Other promising treatments include anti-tumor necrosis factors,Janus kinases inhibitors,and chimeric antigen receptor T cell therapy.This growing armamentarium allows us to imagine a more tailored approach to the treatment of autoimmune hepatitis in the near future.展开更多
In this editorial we comment on the article published by Ning et al,“Role of exosomes in metastasis and therapeutic resistance in esophageal cancer”.Esophageal cancer(EC)represents a significant global health concer...In this editorial we comment on the article published by Ning et al,“Role of exosomes in metastasis and therapeutic resistance in esophageal cancer”.Esophageal cancer(EC)represents a significant global health concern,being the seventh most common and sixth in terms of mortality worldwide.Despite the advances in therapeutic modalities,the management of patients with EC remains challenging,with a 5-year survival rate of only 25%and a limited eligibility for curative surgery due to its late diagnosis.Conventional screening methods are impractical for the early detection of EC,given their either invasive or insensitive nature.The advent of liquid biopsy,with a focus on circulating tumor cells,circulating tumor DNA,and exosomes,heralds a non-invasive avenue for cancer detection.Exosomes,small vesicles involved in intercellular communication,are highlighted as potential biomarkers for EC diagnosis and prognosis.Along with a diverse cargo encompassing various types of RNA,DNA molecules,proteins,and metabolites,exosomes emerge as key players in tumorigenesis,tumor development,and metastasis.Their significance extends to carrying distinctive biomarkers,including microRNAs(miRNAs),long non-coding RNAs,and circular RNAs,underscoring their potential diagnostic and prognostic value.Furthermore,exosomes may be utilized for therapeutic purposes in the context of EC treatment,serving as efficient delivery vehicles for therapeutic agents such as chemotherapeutic medicines and miRNAs.In this editorial we delve into the applications of exosomes for the early detection and treatment of EC,as well as the future perspectives.展开更多
Hepatocelluar carcinoma(HCC) is the most lethal cancer in the world.Most HCC over-express c-Myc,which plays a critical role in regulating cellular growth,differentiation and apoptosis in both normal and neoplastic cel...Hepatocelluar carcinoma(HCC) is the most lethal cancer in the world.Most HCC over-express c-Myc,which plays a critical role in regulating cellular growth,differentiation and apoptosis in both normal and neoplastic cells. c-Myc is among the most frequently overexpressed genes in human cancers.Overexpression of c-Myc in hepatic cells leads to development of hepatocellular carcinoma.Here,we review the current progress in understanding physiologic function and regulation of c-Myc as well as its role in hepatic carcinogenesis and discuss the association of c-Myc activation in chronic hepatitis B infection and the upregulation of HIF-1/VEGF.We also explore the possibility of treating HCC by inhibiting c-Myc and examine the pros and cons of such an approach.Although this strategy is currently not available in clinics,with recent advances in better drug design,pharmacokinetics and pharmacogenetics,inhibition of c-Myc might become a novel therapy for HCC in the future.展开更多
Schizophrenia is a severe psychiatric disorder characterized by emotional,behavioral and cognitive disturbances, and the treatment of schizophrenia is oftencomplicated by noncompliance and pharmacoresistance. The sear...Schizophrenia is a severe psychiatric disorder characterized by emotional,behavioral and cognitive disturbances, and the treatment of schizophrenia is oftencomplicated by noncompliance and pharmacoresistance. The search for thepathophysiological mechanisms underlying schizophrenia has resulted in theproposal of several hypotheses to explain the impacts of environmental, genetic,neurodevelopmental, immune and inflammatory factors on disease onset andprogression. This review discusses the newest insights into the pathophysiologyof and risk factors for schizophrenia and notes novel approaches in antipsychotictreatment and potential diagnostic and theranostic biomarkers. The currenthypotheses focusing on neuromediators (dopamine, glutamate, and serotonin),neuroinflammation, the cannabinoid hypothesis, the gut-brain axis model, andoxidative stress are summarized. Key genetic features, including small nucleotidepolymorphisms, copy number variations, microdeletions, mutations andepigenetic changes, are highlighted. Current pharmacotherapy of schizophreniarelies mostly on dopaminergic and serotonergic antagonists/partial agonists, butnew findings in the pathophysiology of schizophrenia have allowed theexpansion of novel approaches in pharmacotherapy and the establishment ofmore reliable biomarkers. Substances with promising results in preclinical andclinical studies include lumateperone, pimavanserin, xanomeline, roluperidone,agonists of trace amine-associated receptor 1, inhibitors of glycine transporters,AMPA allosteric modulators, mGLUR2-3 agonists, D-amino acid oxidase inhibitorsand cannabidiol. The use of anti-inflammatory agents as an add-on therapy ismentioned.展开更多
基金the Suzhou Medical Center,No.Szlcyxzx202103the National Natural Science Foundation of China,No.82171828+9 种基金the Key R&D Plan of Jiangsu Province(Social Development),No.BE2021652the Subject Construction Support Project of The Second Affiliated Hospital of Soochow University,No.XKTJHRC20210011Wu Jieping Medical Foundation,No.320.6750.2021-01-12the Special Project of“Technological Innovation”Project of CNNC Medical Industry Co.Ltd,No.ZHYLTD2021001Suzhou Science and Education Health Project,No.KJXW2021018Foundation of Chinese Society of Clinical Oncology,No.Y-pierrefabre202102-0113Beijing Bethune Charitable Foundation,No.STLKY0016Research Projects of China Baoyuan Investment Co.,No.270004Suzhou Gusu Health Talent Program,No.GSWS2022028Open Project of State Key Laboratory of Radiation Medicine and Protection of Soochow University,No.GZN1202302.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.
文摘BACKGROUND Massive hemorrhagic ascites caused by endometriosis is exceedingly rare,and the treatment strategy remains controversial.Here,we report a case of endometriosis with massive hemorrhagic ascites treated with a novel triple therapy including conservative surgery,gonadotropin-releasing hormone agonist,and then dienogest.CASE SUMMARY A 28-year-old nulliparous patient was admitted to Shengjing Hospital of China Medical University,and exploratory laparoscopy was performed.A total of 9500 mL of brown ascites was aspirated from the pelvic cavity,the bilateral ovaries strongly adhered to the posterior of the uterus and were fixed to the pelvic floor,and endometriotic cysts were not observed in either ovary.The pelvic and abdominal peritonea were covered with patchy red,white,and brown endometriotic lesions and defects.Partial surgical resection of endometriotic lesions on the peritoneum was performed while we simultaneously collected multiple peritoneal biopsies.The final pathological diagnosis was endometriosis coupled with hemorrhagic necrotic tissue.CONCLUSION Postoperative injection of gonadotropin-releasing hormone agonist was provided three times,followed by dienogest administration,and we will continue to follow up with this ongoing treatment.
文摘Ameloblastoma is a benign but locally aggressive odontogenic neoplasm that accounts for 10% of all tumors arising in the mandible and maxilla (1). Eighty percent of ameloblastomas arise in the mandible, and they are usually found in young adults. It frequently recurs if not adequately
文摘BACKGROUND The 2020 European Association of Urology prostate cancer guidelines recommend androgen deprivation therapy(ADT)in combination with apalutamide and enzalutamide,a new generation of androgen receptor antagonists,as first-line therapy.A decrease in prostate-specific antigen(PSA)levels may occur in the early stages of novel hormonal therapy;however,radionuclide bone imaging may suggest disease progression.During follow-up,PSA,radionuclide bone imaging,and prostate-specific membrane antigen(PSMA)positron emission tomography–computed tomography(PET-CT)are needed for systematic evaluation.CASE SUMMARY We admitted a 56-year-old male patient with metastatic hormone-sensitive prostate cancer.Initial radionuclide bone imaging,magnetic resonance imaging(MRI),and PSMA PET-CT showed prostate cancer with multiple bone metastases.Ultrasound-guided needle biopsy of the prostate revealed a poorly differentiated adenocarcinoma of the prostate with a Gleason score:5+4=9.The final diagnosis was a prostate adenocarcinoma(T4N1M1).ADT with novel hormonal therapy(goseraline sustained-release implant 3.6 mg monthly and apalutamide 240 mg daily)was commenced.Three months later,radionuclide bone imaging and MRI revealed advanced bone metastasis.However,PSMA PET-CT examination showed a significant reduction in PSMA aggregation on the bone,indicating improved bone metastases.Considering that progressive decrease in the presenting lumbar pain,treatment strategies were considered to be effective.CONCLUSION ADT using novel hormonal therapy is effective for treating patients with prostate adenocarcinoma.Careful evaluation must precede treatment plan changes.
文摘Gastric cancer(GC) is a common lethal malignancy.Gastroesophageal junction and gastric cardia tumors are the fastest rising malignancies due to increasing prevalence of obesity and acid reflex in the United States.Traditional chemotherapy remains the main treatment with trastuzumab targeting human epidermal growth factor receptor 2 positive disease.The median overall survival(OS) is less than one year for advanced GC patients; thus,there is an urgent unmet need to develop novel therapy for GC.Although multiple targeted agents were studied,only the vascular endothelial growth factor receptor inhibitor ramucirumab was approved recently by the United States Food and Drug Administration because of its 1.4 mo OS benefit(5.2 mo vs 3.8 mo,P = 0.047) as a single agent; 2.2 mo improvement of survival(9.6 mo vs 7.4 mo,P = 0.017) when combined with paclitaxel in previously treated advanced GC patients.It is the first single agent approved for previously treated GC and the second biologic agent after trastuzumab.Even with limited success,targeted therapy may be improved by developing new biomarkers.Immune therapy is changing the paradigm of cancer treatment and is presently under active investigation for GC in clinical trials.More evidence supports GC stem cells existence and early stage studies are looking for its potential therapeutic possibilities.
基金supported by grants from the DFG(German Research Council)Novartis Pharma Gmb H(Nürnberg+2 种基金Germany)Baxter Innovations Gmb H(ViennaGermany)
文摘Schwann cells are the myelinating glial cells of the peripheral nervous system（PNS）.By establishing lipid-rich myelin sheaths around large-caliber axons,they ensure that electrical signal transmission is accelerated-a process referred to as saltatory signal propagation.Apart from this prominent physiological function,these cells also exert important pathophysiological roles in PNS injuries or dis- eases. In contrast to the central nervous system （CNS）, the adult PNS retains a remarkably high degree of intrinsic re- generation. As a consequence, transected axons and dam- aged myelin sheaths can be repaired and nerve functional- ity can be restored. This spontaneous regenerative capacity depends on （inter） actions of macrophages, neurons, and Schwann cells.
文摘Heart failure with reduced ejection fraction(HFrEF)and nonalcoholic fatty liver disease(NAFLD)are two common comorbidities that share similar pathophysiological mechanisms.There is a growing interest in the potential of targeted therapies to improve outcomes in patients with coexisting HFrEF and NAFLD.This manuscript reviews current and potential therapies for patients with coexisting HFrEF and NAFLD.Pharmacological therapies,including angiotensinconverting enzyme inhibitors/angiotensin receptor blockers,mineralocorticoids receptor antagonist,and sodium-glucose cotransporter-2 inhibitors,have been shown to reduce fibrosis and fat deposits in the liver.However,there are currently no data showing the beneficial effects of sacubitril/valsartan,ivabradine,hydralazine,isosorbide nitrates,digoxin,or beta blockers on NAFLD in patients with HFrEF.This study highlights the importance of considering HFrEF and NAFLD when developing treatment plans for patients with these comorbidities.Further research is needed in patients with coexisting HFrEF and NAFLD,with an emphasis on novel therapies and the importance of a multidisciplinary approach for managing these complex comorbidities.
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.
文摘Chronic hepatitis B constitutes a substantial disease burden worldwide.The steps advocated by the World Health Organization in 2016 to eradicate hepatitis B by 2030 has failed to achieve significant progress,especially with respect to immu-nization coverage and linkage to care.The lack of governmental and public awar-eness regarding the long-term implications of hepatitis B burden cause under-funding of developmental projects.The presently approved treatment modalities have limited efficacy in complete viral eradication,hence the need for newer molecules to achieve functional cure(sustained undetectable hepatitis B surface antigen(HBsAg)and hepatitis B virus DNA in peripheral blood after a finite period of therapy).However,preliminary results from trials of novel therapies show their inadequacy to achieve this end by themselves but better performance with a low baseline serum HBsAg with nucleos(t)ide analogues(NA)treatment which need to be combined with/without pegylated interferon as an immu-nomodulator.Such therapy is limited by cost and adverse events and need to show incremental benefit over the standard of care(long-term NA therapy)with respect to efficacy and drug toxicities,making the development process tenuous.Thus,while such therapies continue to be tested,strategies should still focus on prevention of transmission by non-pharmaceutical measures,vaccination and increasing linkage to care.
文摘Autoimmune hepatitis is an uncommon condition that affects both adults and children and is characterized by chronic and recurrent inflammatory activity in the liver.This inflammation is accompanied by elevated IgG and autoantibody levels.Historically,treatment consists of steroids with the addition of azathioprine,which results in remission in approximately 80%of patients.Despite significant advancements in our understanding of the immune system over the past two decades,few modifications have been made to treatment algorithms,which have remained largely unchanged since they were first proposed more than 40 years ago.This review summarized the various treatment options currently available as well as our experiences using them.Although steroids are the standard treatment for induction therapy,other medications may be considered.Cyclosporin A,a calcineurin inhibitor that decreases T cell activation,has proven effective for induction of remission,but its long-term side effects limit its appeal for maintenance.Tacrolimus,a drug belonging to the same family,has been used in patients with refractory diseases with fewer side effects.Sirolimus and everolimus have interesting effects on regulatory T cell populations and may become viable options in the future.Mycophenolate mofetil is not effective for induction but is a valid alternative for patients who are intolerant to azathioprine.B celldepleting drugs,such as rituximab and belimumab,have been successfully used in refractory cases and are useful in both the short and long term.Other promising treatments include anti-tumor necrosis factors,Janus kinases inhibitors,and chimeric antigen receptor T cell therapy.This growing armamentarium allows us to imagine a more tailored approach to the treatment of autoimmune hepatitis in the near future.
文摘In this editorial we comment on the article published by Ning et al,“Role of exosomes in metastasis and therapeutic resistance in esophageal cancer”.Esophageal cancer(EC)represents a significant global health concern,being the seventh most common and sixth in terms of mortality worldwide.Despite the advances in therapeutic modalities,the management of patients with EC remains challenging,with a 5-year survival rate of only 25%and a limited eligibility for curative surgery due to its late diagnosis.Conventional screening methods are impractical for the early detection of EC,given their either invasive or insensitive nature.The advent of liquid biopsy,with a focus on circulating tumor cells,circulating tumor DNA,and exosomes,heralds a non-invasive avenue for cancer detection.Exosomes,small vesicles involved in intercellular communication,are highlighted as potential biomarkers for EC diagnosis and prognosis.Along with a diverse cargo encompassing various types of RNA,DNA molecules,proteins,and metabolites,exosomes emerge as key players in tumorigenesis,tumor development,and metastasis.Their significance extends to carrying distinctive biomarkers,including microRNAs(miRNAs),long non-coding RNAs,and circular RNAs,underscoring their potential diagnostic and prognostic value.Furthermore,exosomes may be utilized for therapeutic purposes in the context of EC treatment,serving as efficient delivery vehicles for therapeutic agents such as chemotherapeutic medicines and miRNAs.In this editorial we delve into the applications of exosomes for the early detection and treatment of EC,as well as the future perspectives.
基金Supported by the Grants from Taiwan Department of Health for the Center of Excellence for Clinical Trial and Research in Neuroscience(DOH99-TD-B-111-003)
文摘Hepatocelluar carcinoma(HCC) is the most lethal cancer in the world.Most HCC over-express c-Myc,which plays a critical role in regulating cellular growth,differentiation and apoptosis in both normal and neoplastic cells. c-Myc is among the most frequently overexpressed genes in human cancers.Overexpression of c-Myc in hepatic cells leads to development of hepatocellular carcinoma.Here,we review the current progress in understanding physiologic function and regulation of c-Myc as well as its role in hepatic carcinogenesis and discuss the association of c-Myc activation in chronic hepatitis B infection and the upregulation of HIF-1/VEGF.We also explore the possibility of treating HCC by inhibiting c-Myc and examine the pros and cons of such an approach.Although this strategy is currently not available in clinics,with recent advances in better drug design,pharmacokinetics and pharmacogenetics,inhibition of c-Myc might become a novel therapy for HCC in the future.
基金Supported by the Projects Progres of Charles University,No. Q25/LF1 and No. Q27/LF1the Grant Agency of Charles University+1 种基金Czech Republic,No. 34119the Project Ministry of Health,Czech Republic for Conceptual Development of Research Organization,No. 64165.
文摘Schizophrenia is a severe psychiatric disorder characterized by emotional,behavioral and cognitive disturbances, and the treatment of schizophrenia is oftencomplicated by noncompliance and pharmacoresistance. The search for thepathophysiological mechanisms underlying schizophrenia has resulted in theproposal of several hypotheses to explain the impacts of environmental, genetic,neurodevelopmental, immune and inflammatory factors on disease onset andprogression. This review discusses the newest insights into the pathophysiologyof and risk factors for schizophrenia and notes novel approaches in antipsychotictreatment and potential diagnostic and theranostic biomarkers. The currenthypotheses focusing on neuromediators (dopamine, glutamate, and serotonin),neuroinflammation, the cannabinoid hypothesis, the gut-brain axis model, andoxidative stress are summarized. Key genetic features, including small nucleotidepolymorphisms, copy number variations, microdeletions, mutations andepigenetic changes, are highlighted. Current pharmacotherapy of schizophreniarelies mostly on dopaminergic and serotonergic antagonists/partial agonists, butnew findings in the pathophysiology of schizophrenia have allowed theexpansion of novel approaches in pharmacotherapy and the establishment ofmore reliable biomarkers. Substances with promising results in preclinical andclinical studies include lumateperone, pimavanserin, xanomeline, roluperidone,agonists of trace amine-associated receptor 1, inhibitors of glycine transporters,AMPA allosteric modulators, mGLUR2-3 agonists, D-amino acid oxidase inhibitorsand cannabidiol. The use of anti-inflammatory agents as an add-on therapy ismentioned.
