Clinical evolution of antisynthetase syndrome-associated interstitial lung disease after COVID-19 in a man with Klinefelter syndrome:A case report

BACKGROUND This study presents a case of rapidly developing respiratory failure due to antisynthetase syndrome(AS)following coronavirus disease 2019(COVID-19)in a 33-year-old man diagnosed with Klinefelter syndrome(KS).CASE SUMMARY A 33-year-old man with a diagnosis of KS was admitted to the Department of Pulmonary and Critical Care Medicine of a tertiary hospital in China for fever and shortness of breath 2 wk after the onset of COVID-19.Computed tomography of both lungs revealed diffuse multiple patchy heightened shadows in both lungs,accompanied by signs of partial bronchial inflation.Metagenomic next-generation sequencing of the bronchoalveolar lavage fluid suggested absence of pathogen.A biopsy specimen revealed organizing pneumonia with alveolar septal thickening.Additionally,extensive auto-antibody tests showed strong positivity for anti-SSA,anti-SSB,anti-Jo-1,and anti-Ro-52.Following multidisciplinary discussions,the patient received a final diagnosis of AS,leading to rapidly progressing respiratory failure.CONCLUSION This study underscores the clinical progression of AS-associated interstitial lung disease subsequent to viral infections such as COVID-19 in patients diagnosed with KS.

Combination treatment of inflammatory bowel disease:Present status and future perspectives

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.

Role of gut-liver axis and glucagon-like peptide-1 receptor agonists in the treatment of metabolic dysfunction-associated fatty liver disease

Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries.MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma.Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis.The mechanisms involved in maintaining gut-liver axis homeostasis are complex.One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gutliver axis functionality.An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis.Moreover,alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis.Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)are a class of drugs developed for the treatment of type 2 diabetes mellitus.They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis.The mechanisms reported to be involved in this effect include an improved regulation of glycemia,reduced lipid synthesis,β-oxidation of free fatty acids,and induction of autophagy in hepatic cells.Recently,multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment.A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD.This review presents the current understanding of the role of the gutliver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.

Correlation of neutrophil to lymphocyte ratio to severity of coronary artery disease and in-hospital clinical outcomes in patients with acute coronary syndrome: A prospective observational study

Objective:To explore correlation of neutrophil-to-lymphocyte ratio(NLR)to severity of coronary artery disease(CAD)and in-hospital clinical outcomes in patients with acute coronary syndrome(ACS).Methods:In this prospective and observational study,we recruited 500 patients with ACS.For all the eligible patients,demographic details were collected,and laboratory parameters were evaluated.The CAD severity was evaluated in terms of the number of involved vessels.The NLR was calculated based on neutrophils and lymphocytes and the correlation of various risk factors and severity and outcome of CAD was performed.Results:77.2%of Patients was male,and 52%of the patients aged between 55-70 years.Based on the type of ACS,396 out of 500 patients had ST-elevation myocardial infarction.An ascending trend in the white blood cell levels and NLR value was noted as the severity of the ACS increased and the highest white blood cell levels and NLR was noted among classⅣpatients.The mean NLR value among the non-survivors were higher compared to the survivors(9.52±5.72 vs.4.76±2.36;P<0.01).Receiver operating curve showed that the cut-off NLR value was 5.76 with a sensitivity of 75.0%and a specificity of 77.3%.Conclusions:The NLR can be used as an independent prognostic marker in ACS.An elevated NLR value serves as a reliable predictor for short-term complications,notably in-hospital mortality.

Changes in the terminology and diagnostic criteria of non-alcoholic fatty liver disease:Implications and opportunities

Fatty liver disease(FLD)is a highly prevalent pathological liver disorder.It has many and varied etiologies and has heterogeneous clinical course and outcome.Its proper nomenclature and classification have been problematic since its initial recognition.Traditionally,it was divided into two main categories:Alcoholassociated liver disease and nonalcoholic FLD(NAFLD).Among these,the latter condition has been plagued with nomenclature and classification issues.The two main objections to its use have been the use of negative(non-alcoholic)and stigmatizing(fatty)terms in its nomenclature.Numerous attempts were made to address these issues but none achieved universal acceptance.Just recently,NAFLD has received a new nomenclature from an international collaborative effort based on a rigorous scientific methodology.FLD has been renamed steatotic liver disease(SLD),and NAFLD as metabolic dysfunction-associated SLD.Metabolic dysfunction-associated steatohepatitis was chosen as the replacement terminology for non-alcoholic steatohepatitis.This is a significant positive change in the nomenclature and categorization of FLD and will likely have a major impact on research,diagnosis,treatment,and prognosis of the disease in the future.

Assessing the impact of concurrent high-fructose and highsaturated fat diets on pediatric metabolic syndrome:A review

High-saturated fat(HF)or high-fructose(HFr)consumption in children predispose them to metabolic syndrome(MetS).In rodent models of MetS,diets containing individually HF or HFr lead to a variable degree of MetS.Nevertheless,simultaneous intake of HF plus HFr have synergistic effects,worsening MetS outcomes.In children,the effects of HF or HFr intake usually have been addressed individually.Therefore,we have reviewed the outcomes of HF or HFr diets in children,and we compare them with the effects reported in rodents.In humans,HFr intake causes increased lipogenesis,hypertriglyceridemia,obesity and insulin resistance.On the other hand,HF diets promote low grade-inflammation,obesity,insulin resistance.Despite the deleterious effects of simultaneous HF plus HFr intake on MetS development in rodents,there is little information about the combined effects of HF plus HFr intake in children.The aim of this review is to warn about this issue,as individually addressing the effects produced by HF or HFr may underestimate the severity of the outcomes of Western diet intake in the pediatric population.We consider that this is an alarming issue that needs to be assessed,as the simultaneous intake of HF plus HFr is common on fast food menus.

A review of the neurotransmitter system associated with cognitive function of the cerebellum in Parkinson's disease

The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent but partially overlap.The dopaminergic system acts on the anterior brain and is responsible for executive function,working memory,and planning.In contrast,the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial function.Evidence from dopaminergic/cholinergic imaging or functional neuroimaging has shed significant insight relating to the involvement of the cerebellum in the cognitive process of patients with Parkinson’s disease.Previous research has reported evidence that the cerebellum receives both dopaminergic and cholinergic projections.However,whether these two neurotransmitter systems are associated with cognitive function has yet to be fully elucidated.Furthermore,the precise role of the cerebellum in patients with Parkinson’s disease and cognitive impairment remains unclear.Therefore,in this review,we summarize the cerebellar dopaminergic and cholinergic projections and their relationships with cognition,as reported by previous studies,and investigated the role of the cerebellum in patients with Parkinson’s disease and cognitive impairment,as determined by functional neuroimaging.Our findings will help us to understand the role of the cerebellum in the mechanisms underlying cognitive impairment in Parkinson’s disease.

A Clinical Study to Assess the Effectiveness of Oral Combination Kit Therapy in Syndromic Management of Abnormal Vaginal Discharge (FEMINE Study) in Kinshasa, Democratic Republic of Congo

Background: Vaginal discharge is one of most common and nagging problems that women face. About 20% - 25% of women who visit gynecology department complain of vaginal discharge and leucorrhoea. An orally administered combination kit, containing 2 g secnidazole, 1 g azithromycin and 150 mg fluconazole (Azimyn FS Kit), has been successfully evaluated in clinical trials and used in several countries for management syndromic vaginal discharge due to infections. Methods: This is a longitudinal study which aimed to verify the clinical efficacy of the combined oral kit containing secnidazole, azithromycin and fluconazole (Azimyn FS Kit®) in the syndromic treatment of abnormal vaginal discharge in patients received in outpatient consultations in Kinshasa/DR Congo from March to September 2023. Results: Majority of patients had whitish vaginal discharge (51.6%) of average abundance (56.2%), accompanied by pruritus in 72.1% of cases, and dyspareunia in 23.5% of cases and hypogastralgia in 40.2% of cases. One week after treatment with the Azimyn FS® combined kit, at the greatest majority of patients (97.3%), abnormal vaginal discharge had decreased by more than 50% (84.1%). Two weeks after treatment with the Azimyn FS® combined kit, almost all patients (97.3%) no longer had abnormal vaginal discharge which had completely disappeared. Conclusion: A single dose of secnidazole, azithromycin and fluconazole in the form of an oral combi-kit (Azimyn FS Kit) has shown excellent therapeutic effectiveness in the syndromic treatment of abnormal vaginal discharge wherein patients were treated without diagnostic confirmation.

Effects of SARS-CoV-2 infection on incidence and treatment strategies of hepatocellular carcinoma in people with chronic liver disease

BACKGROUND Chronic liver disease(CLD)was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.AIM To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma(HCC)among patients with CLD.METHODS A retrospective,territory-wide cohort of CLD patients was identified from an electronic health database in Hong Kong.Patients with confirmed SARS-CoV-2 infection[coronavirus disease 2019(COVID-19)+CLD]between January 1,2020 and October 25,2022 were identified and matched 1:1 by propensity-score with those without(COVID-19-CLD).Each patient was followed up until death,outcome event,or November 15,2022.Primary outcome was incidence of HCC.Secondary outcomes included all-cause mortality,adverse hepatic outcomes,and different treatment strategies to HCC(curative,non-curative treatment,and palliative care).Analyses were further stratified by acute(within 20 d)and post-acute(21 d or beyond)phases of SARS-CoV-2 infection.Incidence rate ratios(IRRs)were estimated by Poisson regression models.RESULTS Of 193589 CLD patients(>95%non-cirrhotic)in the cohort,55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score matching.Upon 249-d median follow-up,COVID-19+CLD was not associated with increased risk of incident HCC(IRR:1.19,95%CI:0.99-1.42,P=0.06),but higher risks of receiving palliative care for HCC(IRR:1.60,95%CI:1.46-1.75,P<0.001),compared to COVID-19-CLD.In both acute and post-acute phases of infection,COVID-19+CLD were associated with increased risks of allcause mortality(acute:IRR:7.06,95%CI:5.78-8.63,P<0.001;post-acute:IRR:1.24,95%CI:1.14-1.36,P<0.001)and adverse hepatic outcomes(acute:IRR:1.98,95%CI:1.79-2.18,P<0.001;post-acute:IRR:1.24,95%CI:1.13-1.35,P<0.001),compared to COVID-19-CLD.CONCLUSION Although CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC,they were more likely to receive palliative treatment than those without.The detrimental effects of SARS-CoV-2 infection persisted in post-acute phase.

Liver disease in patients with transfusion-dependentβ-thalassemia:The emerging role of metabolism dysfunction-associated steatotic liver disease

In this Editorial,we highlight the possible role that metabolism dysfunction-associated steatotic liver disease(MASLD)may play in the future,regarding liver disease in patients with transfusion-dependent β-thalassemia(TDBT).MASLD is characterized by excessive accumulation of fat in the liver(hepatic steatosis),in the presence of cardiometabolic factors.There is a strong correlation between the occurrence of MASLD and insulin resistance,while its increased prevalence parallels the global epidemic of diabetes mellitus(DM)and obesity.Patients with TDBT need regular transfusions for life to ensure their survival.Through these transfusions,a large amount of iron is accumulated,which causes saturation of transferrin and leads to the circulation of free iron molecules,which cause damage to vital organs(primarily the liver and myocardium).Over the past,the main mechanisms for the development of liver disease in these patients have been the toxic effect of iron on the liver and chronic hepatitis C,for which modern and effective treatments have been found,resulting in successful treatment.Additional advances in the treatment and monitoring of these patients have led to a reduction in deaths,and an increase in their life expectancy.This increased survival makes them vulnerable to the onset of diseases,which until recently were mainly related to the non-thalassemic general population,such as obesity and DM.There is insufficient data in the literature regarding the prevalence of MASLD in this population or on the risk factors for its occurrence.However,it was recently shown by a study of 45 heavily transfused patients with beta-thalassemia(Padeniya et al,BJH),that the presence of steatosis is a factor influencing the value of liver elastography and thus liver fibrosis.These findings suggest that future research in the field of liver disease in patients with TDBT should be focused on the occurrence,the risk factors,and the effect of MASLD on these patients.

Periodontal treatment and microbiome-targeted therapy in management of periodontitis-related nonalcoholic fatty liver disease with oral and gut dysbiosis

A growing body of evidence from multiple areas proposes that periodontal disease,accompanied by oral inflammation and pathological changes in the microbiome,induces gut dysbiosis and is involved in the pathogenesis of nonalcoholic fatty liver disease(NAFLD).A subgroup of NAFLD patients have a severely progressive form,namely nonalcoholic steatohepatitis(NASH),which is characterized by histological findings that include inflammatory cell infiltration and fibrosis.NASH has a high risk of further progression to cirrhosis and hepatocellular carcinoma.The oral microbiota may serve as an endogenous reservoir for gut microbiota,and transport of oral bacteria through the gastro-intestinal tract can set up a gut microbiome dysbiosis.Gut dysbiosis increases the production of potential hepatotoxins,including lipopolysaccharide,ethanol,and other volatile organic compounds such as acetone,phenol and cyclopentane.Moreover,gut dysbiosis increases intestinal permeability by disrupting tight junctions in the intestinal wall,leading to enhanced translocation of these hepatotoxins and enteric bacteria into the liver through the portal circulation.In particular,many animal studies support that oral administration of Porphyromonas gingivalis,a typical periodontopathic bacterium,induces disturbances in glycolipid metabolism and inflammation in the liver with gut dysbiosis.NAFLD,also known as the hepatic phenotype of metabolic syndrome,is strongly associated with metabolic complications,such as obesity and diabetes.Periodontal disease also has a bidirectional relationship with metabolic syndrome,and both diseases may induce oral and gut microbiome dysbiosis with insulin resistance and systemic chronic inflammation cooperatively.In this review,we will describe the link between periodontal disease and NAFLD with a focus on basic,epidemiological,and clinical studies,and discuss potential mechanisms linking the two diseases and possible therapeutic approaches focused on the microbiome.In conclusion,it is presumed that the pathogenesis of NAFLD involves a complex crosstalk between periodontal disease,gut microbiota,and metabolic syndrome.Thus,the conventional periodontal treatment and novel microbiome-targeted therapies that include probiotics,prebiotics and bacteriocins would hold great promise for preventing the onset and progression of NAFLD and subsequent complications in patients with periodontal disease.

Insulin resistance and adipose tissue interactions as the cornerstone of metabolic(dysfunction)-associated fatty liver disease pathogenesis

The relationship between metabolic derangements and fatty liver development are undeniable,since more than 75% of patients with type 2 diabetes mellitus present with fatty liver.There is also significant epidemiological association between insulin resistance(IR)and metabolic(dysfunction)-associated fatty liver disease(MAFLD).For little more than 2 years,the nomenclature of fatty liver of non-alcoholic origin has been intended to change to MAFLD by multiple groups.While a myriad of reasons for which MAFLD is thought to be of metabolic origin could be exposed,the bottom line relies on the role of IR as an initiator and perpetuator of this disease.There is a reciprocal role in MAFLD development and IR as well as serum glucose concentrations,where increased circulating glucose and insulin result in increased de novo lipogenesis by sterol regulatory elementbinding protein-1c induced lipogenic enzyme stimulation;therefore,increased endogenous production of triglycerides.The same effect is achieved through impaired suppression of adipose tissue(AT)lipolysis in insulin-resistant states,increasing fatty acid influx into the liver.The complementary reciprocal situation occurs when liver steatosis alters hepatokine secretion,modifying fatty acid metabolism as well as IR in a variety of tissues,including skeletal muscle,AT,and the liver.The aim of this review is to discuss the importance of IR and AT interactions in metabolic altered states as perhaps the most important factor in MAFLD pathogenesis.

Clinical and pathophysiological understanding of the hepatorenal syndrome:Still wrong or still not exactly right?

The hepatorenal syndrome(HRS)is one major extrahepatic complication of endstage liver diseases.While circulatory dysregulation is considered as primary etiology for HRS,cirrhosis-related(systemic)inflammation and/or cardial dysfunction may also play a key pathogenic role in HRS development.Exclusion of other causes of acute kidney injury(AKI)is required for diagnosis of HRS-AKI by the definition of the International Club of Ascites.However,the pathophysiology of HRS is not understood completely and there are still limited therapeutic options.Reversibility of renal dysfunction after liver transplantation indicates that HRS-AKI is a functional disorder caused by altered cellular function.The interplay between systemic inflammation and the onset of kidneyrelated hypometabolism may have a key role and needs to be studied in depth.This minireview challenges simplified views of the HRS in the context of diagnostics and therapy stressing the need for further evidence to advance the knowledge on this syndrome.

Realizing the potential of exploiting human IPSCs and their derivatives in research of Down syndrome

Down syndrome(DS)is a genetic condition characterized by intellectual disability,delayed brain development,and early onset Alzheimer’s disease.The use of primary neural cells and tissues is important for understanding this disease,but there are ethical and practical issues,including availability from patients and experimental manipulability.Moreover,there are significant genetic and physiological differences between animal models and humans,which limits the translation of the findings in animal studies to humans.Advancements in induced pluripotent stem cells(iPSC)technology have revolutionized DS research by providing a valuable tool for studying the cellular and molecular pathologies associated with DS.Induced pluripotent stem cells derived from cells obtained from DS patients contain the patient’s entire genome including trisomy 21.Trisomic iPSCs as well as their derived cells or organoids can be useful for disease modeling,investigating the molecular mechanisms,and developing potential strategies for treating or alleviating DS.In this review,we focus on the use of iPSCs and their derivatives obtained from DS individuals and healthy humans for DS research.We summarize the findings from the past decade of DS studies using iPSCs and their derivatives.We also discuss studies using iPSC technology to investigate DS-associated genes(e.g.,APP,OLIG1,OLIG2,RUNX1,and DYRK1A)and abnormal phenotypes(e.g.,dysregulated mitochondria and leukemia risk).Lastly,we review the different strategies for mitigating the limitations of iPSCs and their derivatives,for alleviating the phenotypes,and for developing therapies.

Persistent Xerophthalmia in a Patient with Rheumatological Disease and Priiviary Sjogren’s Syndrome: Case Report from Northern Brazil

This case study aims to contribute to the literature in order to highlight the importance of this collaboration between medical specialties. A female patient R.N.N. F, age 66, from the city of Manaus, with a previous diagnosis of Sjogren’s syndrome in regular follow-up by the Rheumatology team at the Araujo Lima outpatient clinic and referred to the Ophthalmology sector for complementary evaluation related to visual discomfort. The fundoscopy performed in the patient was within normal limits, but the symptoms experienced by her proved to be an important clinical finding, which has ratified the need for regular and multidisciplinary follow-up. This report unequivocally demonstrates that even in the face of tests considered within the expected limits for a given population, the clinical presentation can be specific and particular for each analyzed individual. Early screening exams should contemplate the patient in a holistic and individualized way whenever possible.

Rationale of Cross-Sectional Descriptive Study on Clinical Effectiveness of Oral Combination Therapy Based on Secnidazole, Azithromycin and Fluconazole in Syndromic Treatment of Abnormal Vaginal Discharge in Kinshasa/DR Congo

Background: Vaginal discharge is one of the most common troubles faced by childbearing age women. About 20% - 25% of women who visit service of gynecology complain of vaginal discharge and leucorrhoea. Management of vaginal discharge in low-income countries generally depends on syndromic approach, which limits the understanding of specific responsible agents. Thus targeted management is based on the identification of causal organism and targeting of therapy against it, while syndromic management is based on presence of high risk factors. Thus the oral combination kit (Azimyn FS Kit®) offers convenience of a one-day treatment compared to other multidose treatments, which will also ensure high patient adherence to treatment, thus increasing chances of desired results. Due to its widespread use, it is proposed to evaluate the effectiveness of this oral association kit therapy in management of vaginal discharge in the population of our milieu in the Democratic Republic of Congo (DRC) particularly those received in outpatient consultation in some medical facilities in city of Kinshasa. Expensive laboratory tests and the associated waiting period for result mean that patient remains without treatment while waiting for test results. Therefore, by adopting a syndromic management approach, patient’s eligibility for treatment will be decided based on abnormal vaginal discharge, their characteristics, severity and other presentations symptomatic. This approach will also avoid losing sight of patients during follow-up and will help to reduce financial burden for patients. Objectives: To determine the efficacy and safety of oral combination kit therapy containing secnidazole, azithromycin and fluconazole (Azimyn FS Kit®) in syndromic treatment of abnormal vaginal discharge in patients received in outpatient consultation in some medical facilities in the city of Kinshasa;to measure rate of recurrence of abnormal vaginal discharge in these patients. And to identify the adverse effects observed in these patients who received treatment with the combined oral kit containing secnidazole, azithromycin and fluconazole (Azimyn FS Kit®) in outpatient consultation in some medical facilities in the city of Kinshasa. Methods: It will be a cross-sectional descriptive study. Sample size will be 319 women of childbearing age who consult the gynecology department with complaint of abnormal vaginal discharge and suspicion of vaginal infection, who agree to abstain from sex during treatment and who have given their written consent to use their personal and/or health data in the study. Conclusion: A study on clinical efficacy of oral combination therapy based on secnidazole, azithromycin and fluconazole is beneficial.

Exploring the potential mechanisms of impairment on genitourinary system associated with coronavirus disease 2019 infection:Bioinformatics and molecular simulation analyses

Objective:The novel coronavirus(severe acute respiratory syndrome coronavirus 2)has been spreading worldwide since December 2019,posing a serious danger to human health and socioeconomic development.A large number of clinical trials have revealed that coronavirus disease 2019(COVID-19)results in multi-organ damage including the urogenital system.This study aimed to explore the potential mechanisms of genitourinary damage associated with COVID-19 infection through bioinformatics and molecular simulation analysis.Methods:We used multiple publicly available databases to explore the expression patterns of angiotensin-converting enzyme 2(ACE2),transmembrane serine protease 2(TMPRSS2),and CD147 in major organs in the healthy and disease-specific populations,particularly the genitourinary organs.Single-cell RNA sequencing was used to analyze the cell-specific expression patterns of ACE2,TMPRSS2,CD147,cytokine receptors,and cytokine interacting proteins in genitourinary organs,such as the bladder,kidney,prostate,and testis.Additionally,gene set enrichmentanalysis was used to investigate the relationship between testosterone levels and COVID-19 vulnerability in patients with prostate cancer.Results:The results revealed that ACE2,TMPRSS2,and CD147 were highly expressed in normal urogenital organs.Then,they were also highly expressed in multiple tumors and chronic kidney diseases.Additionally,ACE2,TMPRSS2,and CD147 were significantly expressed in a range of cells in urogenital organs according to single-cell RNA sequencing.Cytokine receptors and cytokine interacting proteins,especially CCL2,JUN,and TIMP1,were commonly highly expressed in urogenital organs.Finally,gene set enrichment analysis results showed that high testosterone levels in prostate cancer patients were significantly related to the JAK-STAT signaling pathway and the Toll-like receptor signaling pathway which were associated with COVID-19.Conclusion:Our study provides new insights into the potential mechanisms of severe acute respiratory syndrome coronavirus 2 damage to urogenital organs from multiple perspectives,which may draw the attention of urologists to COVID-19 and contribute to the development of targeted drugs.

Immune checkpoint inhibitor therapy-induced autoimmune polyendocrine syndrome typeⅡand Crohn's disease:A case report

BACKGROUND The development of immune checkpoint inhibitors(ICIs)has heralded a new era in cancer treatment,enabling the possibility of long-term survival in patients with metastatic disease.Unfortunately,ICIs are increasingly implicated in the development of autoimmune diseases.CASE SUMMARY We present a man with squamous cell carcinoma of the oropharynx on a combination of teriprizumab,docetaxel,and cisplatin therapy who developed autoimmune polyendocrine syndrome typeⅡ(APS-2)including thyroiditis and type 1 diabetes mellitus and Crohn’s disease(CD).He developed thirst,abdominal pain,and fatigue after two-week treatment with the protein 1 ligand inhibitor teriprizumab.Biochemistry confirmed APS-2 and thyrotoxicosis.He was commenced on an insulin infusion.However,his abdominal pain persisted.Follow-up surgery confirmed CD and his abdominal pain was relieved by mesalazine.He was continued on insulin and mesalazine therapy.CONCLUSION Immunotherapy can affect all kinds of organs.When clinical symptoms cannot be explained by a single disease,clinicians should consider the possibility of multisystem damage.

Protocol to study the effects of AMPK-mTOR/PINK-Parkin dual signaling pathways on the formation of coronary heart disease showing blood stasis symptom pattern based on traditional Chinese medicine theory of“heart governing blood and vessels”

In this study,we aim to combine gene transfection techniques with the modeling methods previously employed by the research group to deeply investigate the corresponding theories of traditional Chinese medicine regarding“myocardial energy metabolism”and“aortic thrombosis”.Our goal is to elucidate the biological mechanism underlying the occurrence and development of coronary heart disease with blood stasis syndrome from the perspectives of“heart and vessels”and“Qi(in traditional Chinese medicine,it refers to the most fundamental and subtle substances that constitute the human body and maintain life activities.At the same time,it also has the meaning of physiological function.In terms of traditional Chinese medicine,Qi and different words are used together to express different meanings)and blood”.The research content is divided into four modules as follows:1.establishment of an animal model of coronary heart disease with blood stasis syndrome through fibrinogen overexpression.2.Investigation of the mitochondrial quality control system in coronary heart disease with blood stasis syndrome under fibrinogen overexpression.3.Study of platelet autophagy in coronary heart disease with blood stasis syndrome under fibrinogen overexpression.4.Examination of the relationship between the AMPK-mTOR pathway and metabolism in platelet autophagy of coronary heart disease with blood stasis syndrome under fibrinogen overexpression.Ninety-six Sprague Dawley rats will be randomly assigned to the following groups:control group,model group,fibrinogen group and adeno-associated virus group.All rats will undergo a 14-week model construction process,and modern molecular biology methods will be employed to evaluate the model and examine relevant research indicators.The obtained data will be analyzed according to a predefined statistical analysis plan.

On Chinese-English Translation of Disease and Syndrome Terms in Shang Han Lun from the Perspective of Functional Equivalence Theory

Shang Han Lun is one of the most famous and important traditional medical books in China,so many translation versions of it have emerged.Based on the comparison of examples taken from two of these translation versions,Young Jie De ' s Shang Han Lun Explained and Huang Hai s Introduction to Treatise on Exogenous Febrile Disease,the paper points out that Nida s Functional Equivalence Theory provides a new idea for the translation of Disease and Syndrome Terms in TCM that literal translation,liberal translation and transliteration can be adopted appropriately to make readers of translation versions understand TCM accurately and easily.