Tuberculosis(TB)is an airborne infection caused by Mycobacterium tuberculosis that usually affects the lungs.Timely treatment of active TB,diagnosis and prevention of latent TB are very important.However,extrapulmonar...Tuberculosis(TB)is an airborne infection caused by Mycobacterium tuberculosis that usually affects the lungs.Timely treatment of active TB,diagnosis and prevention of latent TB are very important.However,extrapulmonary TB affects almost any tissues around the eye and orbit,and it then requires a high degree of suspicion to accurately diagnose.Diagnostic delays are common and may lead to morbidity.For ophthalmologists and infectious disease specialists,it is important to work together to accurately diagnose and treat ocular tuberculosis(OTB)to prevent vision loss.This review reports the latest advanced diagnostic methods for active TB and latent TB as well as various known manifestations of 0TB.Important elements of diagnosis and treatment are also reviewed.展开更多
Experts lack knowledge of periocular tuberculosis（TB） in China. Nested polymerase chain reaction（PCR） shows advantages in diagnosis of extrapulmonary TB. Our study aims to explore the clinical and laboratory featu...Experts lack knowledge of periocular tuberculosis（TB） in China. Nested polymerase chain reaction（PCR） shows advantages in diagnosis of extrapulmonary TB. Our study aims to explore the clinical and laboratory features of PCR-confirmed periocular TB. We retrospectively reviewed medical records of presumptive periocular TB and performed nested PCR test to confirm diagnosis. Nine cases were recruited. Clinical symptoms were chronic and insidious. Eight cases achieved favorable visual acuity, while one underwent enucleation due to fungalTB panophthalmitis. Sensitivity of caseous necrosis, acidfast bacilli（AFB） staining and interferon γ release assay（T-SPOT） test are 33.3%, 44.4% and 85.7% respectively. Low lymphocyte percentage（P=0.019） and high monocytelymphocyte ratio（P=0.042） positively correlate with AFB staining. Male gender（P=0.048） and Langhans giant cell（P=0.048） positively correlate with caseous necrosis. To conclude, traditional TB ancillary tests are not as sensitive as nested PCR technique. Several factors facilitate diagnosis including male gender, decreased lymphocytes, and typical Langhans giant cells.展开更多
Aim: To study the frequency of various ocular manifestations in diagnosed cases of active pulmonary and extra pulmonary tuberculosis in two different major hospitals in Nepal. Method: A hospital based, cross sectional...Aim: To study the frequency of various ocular manifestations in diagnosed cases of active pulmonary and extra pulmonary tuberculosis in two different major hospitals in Nepal. Method: A hospital based, cross sectional descriptive study was conducted in the National Tuberculosis Centre, Bhaktapur and BP Koirala Lions Center for Ophthalmic Studies (BPKLCOS), Tribhuvan University Teaching Hospital (TUTH), Kathmandu, Nepal during a period of 18 months from February 2010 to August 2011. Diagnosed cases of systemic tuberculosis were evaluated by ophthalmologists for any ophthalmic manifestations. Results: There were 585 cases in the study. 399 (68%) were cases of pulmonary tuberculosis and 186 (32%) were that of extra pulmonary tuberculosis. Ocular manifestations were seen in 2.6% (15 patients) of the study population;1.25% (6 patients) in cases of pulmonary tuberculosis and 5.37% (9 patients) in extra pulmonary tuberculosis cases. Uveitis (40%) followed by papilloedema (33%) were the two most common ocular manifestations. Of the 25 affected eyes of 15 patients, 2 eyes of patients with choroiditis involving the macular area were legally blind. Majority of the affected cases (67%) had bilateral involvement. Conclusion: Ocular manifestations in tuberculosis vary greatly ranging from mild episcleritis to potentially blinding posterior uveitis, clinical acumen being of great importance in timely diagnosis and treatment so that vision threatening complications can be prevented. Ocular manifestations are more common in extra pulmonary tuberculosis cases.展开更多
Background:Skeletal tuberculosis(TB)remains a persistent clinical and research chal-lenge due to its chronic course,osteolytic destruction,and the limitations of existing animal models,which often require high-level b...Background:Skeletal tuberculosis(TB)remains a persistent clinical and research chal-lenge due to its chronic course,osteolytic destruction,and the limitations of existing animal models,which often require high-level biosafety containment or fail to repli-cate human skeletal pathology.Methods:This study developed a biosafe,accessible,and versatile murine model of skeletal TB using Mycobacterium smegmatis,a fast-growing,nonpathogenic myco-bacterial species with high genomic homology to Mycobacterium tuberculosis.Three infection routes-subperiosteal calvarial injection,intratibial injection,and intra-cardiac inoculation-were systematically evaluated for their ability to induce lo-calized versus disseminated bone infection under standard biosafety level(BSL)-1 conditions.Results:Subperiosteal calvarial and intratibial injection of M.smegmatis induced local-ized bone lesions characterized by osteolysis,sequestrum formation,granulomatous inflammation,and increased osteoclast activity.Intratibial infection additionally trig-gered compartment-specific immune responses,including neutrophil and macrophage expansion,transient B-cell depletion,and activation of interferon-γ^(+)(IFN-γ^(+))T cells,reflecting active immune remodeling at the infection site.Systemic dissemination via intracardiac injection reproducibly generated progressive vertebral and tibial bone destruction with organized granuloma formation and immune cell infiltration but without prominent sequestrum formation.Compared to intratibial infection,intracar-diac delivery exhibited lower intragroup variability and more closely recapitulated the diffuse progression of extrapulmonary skeletal tuberculosis.Conclusions:This M.smegmatis-based murine model provides a straightforward,reliable,and immunopathologically relevant platform for exploring host-pathogen dynamics,immune-driven bone destruction,and early-stage therapeutic testing in skeletal TB,all within standard BSL-1 laboratories.This model fills a critical gap by enabling BSL-1 research into skeletal TB mechanisms and drug development.展开更多
BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complet...BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complete bone regeneration often remains unachieved,contributing to subsequent orthopedic complications.AIM To investigate the efficacy and safety of pamidronate in promoting bone regeneration following surgical treatment of experimental animal tuberculous osteitis.METHODS A controlled randomized basic study of rabbit femoral tuberculosis induced by Mycobacterium tuberculosis strain H37Rv included surgical removal of infected tissue and implantation of osteoinductive bone grafts with the following animal allocation to one of three groups:(1)Bisphosphonates alone;(2)Bisphosphonates combined with anti-tuberculous therapy;and(3)Anti-tuberculous therapy alone.The control group consisted of animals that received no surgical or medical treatment.Clinical evaluations,biochemical markers,micro-computed tomography imaging,and histomorphometry analyses were conducted at 3 months and 6 months postoperatively.RESULTS Pamidronate treatment significantly reduced early implant resorption,increased osteoblastic activity,improved trabecular bone regeneration,and maintained graft integrity compared to the anti-tuberculous therapy-only group.Histologically,pamidronate led to enhanced vascular remodeling and increased bone matrix formation.Crucially,bisphosphonate therapy demonstrated safety,compatibility with anti-tuberculous medications,and did not exacerbate tuberculous inflammation.Furthermore,micro-computed tomography analysis revealed a significant increase in trabecular thickness and density in pamidronate-treated groups,underscoring the anabolic effects of bisphosphonates.Morphometric evaluation confirmed a marked reduction in osteoclast number and activity at graft interfaces.These combined radiological,histological,and biochemical data collectively demonstrate the efficacy of pamidronate as an adjunctive agent in enhancing bone repair outcomes following surgical intervention for tuberculous osteitis.CONCLUSION A single intravenous dose of pamidronate significantly enhances bone regeneration and prevents implant resorption following surgical treatment of tuberculous osteitis.The following prospective studies are needed.展开更多
Tuberculosis(TB),one of the oldest infectious diseases caused by Mycobacterium tuberculosis,poses a considerable challenge to global public health.There are approximately 10 million new TB cases worldwide annually,and...Tuberculosis(TB),one of the oldest infectious diseases caused by Mycobacterium tuberculosis,poses a considerable challenge to global public health.There are approximately 10 million new TB cases worldwide annually,and TB claims the lives of nearly 3 million people each year,making it one of the leading causes of death from a single infectious disease[1].China ranks third globally in terms of TB burden,with approximately 733,000 TB cases reported in 2023[2].Based on the ecological model of health determinants developed by Whitehead and Dahlgren,health determinants can be classified into direct causes.展开更多
AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided...AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided into four equal groups(n=6/group)as follows:healthy group(HG),ATP-only group(ATPG),sildenafil-onlygroup(SILG),and ATP+sildenafil group(ATP+SLD).ATPG andATP+SLD groups were injected intraperitoneally with ATP(4 mg/kg),while SILG and HG groups were injected withsaline(0.9%NaCl)by the same route as a solvent.One hourafter the administration of ATP and solvent,sildenafil(10 m g/k g)was administered orally to the SILG andATP+SLD groups.This procedure was repeated once a dayfor 4wk.The animals were then sacrificed,eyeballs wereremoved and oxidant and antioxidant parameters weremeasured biochemically.Additionally,the ocular tissueswere evaluated histopathologically.RESULTS:Sildenafil increased oxidant(malondialdehyde)levels and decreased antioxidant levels(total glutathione,superoxide dismutase,catalase)in rat ocular tissues andcaused severe oxidative stress.In addition,sildenafil hasbeen shown histopathologically to cause oxidative damagein retinal layers.ATP treatment suppressed oxidative stressand attenuated histopathological damage in the retinal layers.CONCLUSION:ATP protects retinal tissue againstsildenafil-induced ocular oxidative damage in rats andmay contribute to the development of novel approaches toprevent or treat this damage.展开更多
Liver transplantation is a life-saving procedure for patients with end-stage liver diseases and acute liver failure.With advances in surgical techniques and immunosuppressive regimens,patient survival rates have signi...Liver transplantation is a life-saving procedure for patients with end-stage liver diseases and acute liver failure.With advances in surgical techniques and immunosuppressive regimens,patient survival rates have significantly improved.While the systemic complications of post-transplantation are well recognized,ophthalmic manifestations remain underreported.Ophthalmic complications can significantly impair visual function and increase morbidity in these patients.Prolonged immunosuppression makes the patients susceptible to the opportunistic pathogens such as Cytomegalovirus,Candida,Aspergillus,etc.Other common findings include dry eye disease,cataracts and retinal vascular complications which further contribute to the long-term morbidity in these patients.Early ophthalmic evaluation and prompt management are essential to prevent irreversible vision loss and improve post-transplant outcomes.High index of suspicion and multidisciplinary approach is essential to facilitate early diagnosis and treatment.This review highlights the range of ophthalmic complications observed in liver transplant recipients and underscores the need for future research focused on understanding the underlying pathophysiological mechanisms and refining the prophylactic protocols to improve outcomes in this unique patient population.展开更多
BACKGROUND Dry eye disease(DED)is a multifactorial ocular surface disorder with rising prevalence.It is closely related to systemic health and psychological factors,such as sleep and mood disorders,which significantly...BACKGROUND Dry eye disease(DED)is a multifactorial ocular surface disorder with rising prevalence.It is closely related to systemic health and psychological factors,such as sleep and mood disorders,which significantly impact the quality of life of patients.AIM To explore the correlations between ocular surface function,sleep quality,and anxiety/depression in patients with DED.METHODS This was a cross-sectional investigative study that included 358 patients with DED between January 2022 and January 2025.Ocular surface was assessed using the ocular surface disease index(OSDI),tear film break-up time,fluorescein staining score,and Schirmer I test.The Pittsburgh Sleep Quality Index(PSQI),Self-Rating Anxiety Scale(SAS),and Self-Rating Depression Scale(SDS)were used to evaluate sleep quality and anxiety/depression levels.Correlation and linear regression analyses were used to explore the relationships.RESULTS The mean PSQI score of the patients was 9.94±2.18;the mean SAS score was 47.30±4.90,and the mean SDS score was 50.08±5.52.These suggested a prevalence of sleep and psychological abnormalities.There was a significant correlation between the indicators of ocular surface function(OSDI,tear film break-up time,fluorescein staining,and Schirmer I test)and PSQI,SAS,and SDS scores(P<0.05).Moreover,multiple regression revealed that age≥50 years(β=1.55,P=0.029),PSQI scores(β=0.58,P<0.001),SAS scores(β=0.17,P=0.017),and SDS scores(β=0.15,P=0.019)were independent predictors of the OSDI scores.CONCLUSION Ocular surface function in patients with DED is closely related to sleep quality and anxiety/depression,emphasizing the need for holistic clinical management.展开更多
Tuberculosis(TB)continues to pose a significant threat to global public health,necessitating rapid and precise diagnostic methods and comprehensive detection of antimicrobial resistance(AMR)to facilitate timely clinic...Tuberculosis(TB)continues to pose a significant threat to global public health,necessitating rapid and precise diagnostic methods and comprehensive detection of antimicrobial resistance(AMR)to facilitate timely clinical management.Traditional diagnostic techniques suffer from extended turnaround times and limited ability to comprehensively profile AMR,often resulting in delayed therapeutic interventions.Highthroughput sequencing(HTS)technologies have revolutionized pathogen research by significantly improving diagnostic speed and accuracy.In the context of TB,diverse sequencing strategies and platforms are being employed to fulfill specific research goals,ranging from elucidating the molecular mechanisms underlying AMR to characterizing the genomic diversity among clinical isolates.This review systematically examines current progress in the application of HTS for rapid pathogen identification,comprehensive AMR profiling,epidemiological studies,advances in novel drugs,and vaccine development.Furthermore,we address existing technological limitations and bioinformatics challenges and explore the future directions necessary for effectively integrating HTS-based methodologies into global TB control efforts.展开更多
This report presents a forensic evaluation of a case involving blindness(visual acuity grade 5)following a bee/wasp sting to the left eye.Through systematic analysis of the patient’s multiple hospital admissions,post...This report presents a forensic evaluation of a case involving blindness(visual acuity grade 5)following a bee/wasp sting to the left eye.Through systematic analysis of the patient’s multiple hospital admissions,postoperative follow-up data,and a review of the pathological mechanisms of ocular injury caused by bee venom,this study comprehensively assesses the injury characteristics,treatment course,and visual outcomes.Bee venom induces severe complications such as corneal damage,uveitis,cataract,and secondary glaucoma through multiple mechanisms including direct cytotoxicity,immune-inflammatory responses,and enzymatic hydrolysis.Despite interventions including anterior chamber irrigation,phacoemulsification with intraocular lens implantation,and antiglaucoma surgery,the affected eye ultimately lost light perception.Forensic examination confirmed the absence of light perception in the left eye and abnormal visual pathway function,consistent with clinical observations.According to the relevant Chinese disability assessment standard(JR/T 0083-2013,Article 4.2.2),the injury was classified as grade 7 disability.This study provides an in-depth discussion of the mechanisms and key forensic identification points in bee-sting-induced blindness,offering a scientific reference for similar forensic clinical cases.展开更多
Objective To determine the proportions of drug-resistant tuberculosis(TB),its trends,and the drug resistance-conferring mutations among patients with pulmonary TB aged 10-24 years in China.Methods The data of patients...Objective To determine the proportions of drug-resistant tuberculosis(TB),its trends,and the drug resistance-conferring mutations among patients with pulmonary TB aged 10-24 years in China.Methods The data of patients with pulmonary TB were retrieved from a national drug-resistant TB survey for analysis.Joinpoint regression software was used to analyze time trends.We also used whole genome sequencing to analyze the lineages and drug resistance-conferring mutations of 621 isolates.Results Among 4,235 patients with pulmonary TB,the proportion of new cases of multidrug-resistant tuberculosis(MDR-TB)was 3.18%(95%confidence interval[CI]:2.37-4.15)for adolescents and 3.76%(95%CI:3.03-4.60)for young adults;for previously treated patients,MDR-TB accounted for 11.25%(95%CI:5.28-20.28)of adolescents and 11.05%(95%CI:6.88-16.55)of young adults.The proportion of patients with MDR-TB remained stable among both new and previously treated patients aged 10-24 years during the study period.Through whole genome sequencing,we found that the most common mutations in the MDR-TB strains were Ser315Thr in the katG gene(71.74%)and Ser450Leu in the rpoB gene(50.00%).Conclusion This study revealed a high proportion of MDR-TB among adolescents and young adults,indicating that urgent and comprehensive measures are needed to reduce the emergence and transmission of drug-resistant TB among this population in China.展开更多
AIM:To ascertain the pattern of ocular morbidity in a population of primary school children in rural Kenya as it is a prerequisite for planning effective preventive and therapeutic strategies.METHODS:A cross-sectional...AIM:To ascertain the pattern of ocular morbidity in a population of primary school children in rural Kenya as it is a prerequisite for planning effective preventive and therapeutic strategies.METHODS:A cross-sectional survey of ocular symptoms and clinical eye examinations were performed in a sample of 35 rural primary schools in the semi-arid region of Kajiado West sub-county in S.W.Kenya,amongst a seminomadic tribe(Maasai).Students in Grades 1-8 were included.Visual acuity was measured using the Snellen“tumbling E”chart at 6 m.Children with symptoms of refractive error underwent non-cycloplegic refraction.RESULTS:A total of 2036 children(1084 males)between the ages of 4-20y were examined.Conjunctival actinic changes were present in 22%(442/2036).Nine cases were seen with a potential squamous carcinoma.No overt classical ocular signs of vitamin A deficiency were noted,although 181(8.9%)children complained of nyctalopia.Three hundred thirty-six(16.5%)children had a visual acuity worse than 6/12 in either eye,were unable to read N10 near text at 40 cm or had symptoms suggestive of refractive error.Refractive data led to an estimate of hyperopia of+1.00 D or more in 3.9%and of myopia of-0.50 D or more in either eye in 3.0%of the study population.CONCLUSION:Solar exposure-and dust-related conjunctival pathology is common.As this may develop into potentially sight-or even life-threatening conditions,it warrants further study,and preventive strategies may be needed.Complaints of nyctalopia were common and could suggest vitamin A deficiency.The prevalence of refractive errors is low in this rural African population.展开更多
Objective Post tuberculosis lung disease(PTLD)manifests in various forms,including tuberculosisassociated chronic obstructive pulmonary disease(TB-COPD),yet the clinical features of PTLD remain undercharacterized.This...Objective Post tuberculosis lung disease(PTLD)manifests in various forms,including tuberculosisassociated chronic obstructive pulmonary disease(TB-COPD),yet the clinical features of PTLD remain undercharacterized.This study aimed to assess longitudinal changes in lung function over a 5-year period and to identify predictors of airflow obstruction in a cohort of patients treated for active pulmonary TB.Methods Patients with active pulmonary TB were enrolled in this study and were followed during treatment,at treatment completion and five years post-treatment.Assessments included lung function and chest CT,analyzing longitudinal trends and airflow obstruction risk factors.Results Among 53 patients(mean age 36.9±13.9 years;64.2%male),7 patients(13.2%)exhibited airflow obstruction.At the 5-year follow-up,the mean FEV_(1)/FVC declined significantly(76.27%±12.04%vs.80.23%±11.02%,P<0.001)and 9 patients(17.0%)exhibited airflow obstruction.Seven of these patients predominantly showed air trapping consistent with small airway disease on chest CT,aligning with TB-COPD phenotype.Notably,four young-to-middle-aged patients(<60 years old)had persistent obstruction over the five years.Conclusion The initial test revealed that 13.2%of patients presented with airflow obstruction.By the 5-year follow-up,this proportion had increased to 17.0%,with most cases demonstrating imaging findings aligning with TB-COPD,even among younger,non-smoking individuals.These findings emphasize the importance of long-term follow-up and routine lung function assessments in TB survivors.展开更多
Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglio...Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglion cells and their axons,leading to axonal transport dysfuntion,subsequently causing secondary damage to anterior or posterior ends of the visual system.Accordingly,recent evidence indicates that glaucoma is a degenerative disease of the central nervous system that causes damage throughout the visual pathway.However,the effects of glaucoma on synaptic plasticity in the primary visual cortex remain unclear.In this study,we established a mouse model of unilateral chronic ocular hypertension by injecting magnetic microbeads into the anterior chamber of one eye.We found that,after 4 weeks of chronic ocular hypertension,the neuronal somas were smaller in the superior colliculus and lateral geniculate body regions of the brain contralateral to the affected eye.This was accompanied by glial cell activation and increased expression of inflammatory factors.After 8 weeks of ocular hypertension,we observed a reduction in the number of excitatory and inhibitory synapses,dendritic spines,and activation of glial cells in the primary visual cortex contralateral to the affected eye.These findings suggest that glaucoma not only directly damages the retina but also induces alterations in synapses and dendritic spines in the primary visual cortex,providing new insights into the pathogenesis of glaucoma.展开更多
AIM:To investigate the clinical characteristics and treatment outcomes,including visual function and overall survival(OS)of patients with ocular adnexal diffuse large B-cell lymphoma(OA-DLBCL).METHODS:This retrospecti...AIM:To investigate the clinical characteristics and treatment outcomes,including visual function and overall survival(OS)of patients with ocular adnexal diffuse large B-cell lymphoma(OA-DLBCL).METHODS:This retrospective cohort study enrolled 29 patients diagnosed with OA-DLBCL based on histopathological biopsy between 2006 and 2023.Patients were stratified into two subgroups:primary OA-DLBCL(no prior history of lymphoma)and secondary OA-DLBCL(history of DLBCL at non-ocular adnexal sites).OS was defined as the time interval from OA-DLBCL diagnosis to death from any cause.Survival analysis was performed using the Kaplan–Meier method,and prognostic factors affecting OS were identified using multivariate Cox proportional hazards regression with a stepwise selection approach.RESULTS:The cohort included 24 patients with primary OA-DLBCL(13 males,11 females;mean age:61.36±18.29y)and 5 patients with secondary OA-DLBCL(2 males,3 females;mean age:50.94±18.17y).Among the primary OA-DLBCL subgroup,12 patients(50%)presented with advanced disease(Ann Arbor stage IIIE–IV),and 16 patients(66%)were classified as T4 disease according to the tumor-node-metastasis(TNM)staging system.The mean final visual acuity was 1.72±1.10 in the primary group and 0.90±1.18 in the secondary group.The 5-year OS rate for the entire cohort was 27.7%.Multivariate analysis identified five factors significantly associated with poor survival outcomes:epiphora[adjusted hazard ratio(aHR),36.95],atherosclerotic cardiovascular disease(aHR,10.08),human immunodeficiency virus(HIV)infection(aHR,12.47),M1 stage(aHR,6.99),and secondary OA-DLBCL(aHR,6.03;all P<0.05).The median OS was 1.68y for primary OA-DLBCL and 1.12y for secondary OA-DLBCL.CONCLUSION:A substantial proportion of patients with primary OA-DLBCL present with advanced-stage disease at diagnosis.Epiphora,atherosclerotic cardiovascular disease,HIV infection,M1 stage,and secondary OA-DLBCL are independent prognostic factors for poor survival outcomes.These findings emphasize the urgent need for optimized therapeutic strategies and early screening protocols to improve the management of OA-DLBCL,particularly in developing countries.展开更多
To assess the effectiveness of vaccination in contaminated environments,this study introduces a modeling framework that encompasses two transmission routes,namely direct human-to-human contact and indirect human-to-en...To assess the effectiveness of vaccination in contaminated environments,this study introduces a modeling framework that encompasses two transmission routes,namely direct human-to-human contact and indirect human-to-environment contact,as well as the implementation of new M72/AS01_(E)vaccine.Motivated by this,a coupled age-structured tuberculosis(TB)model is proposed.Its well-posedness requirement is verified using the integrated semigroup theory.Furthermore,this study presents a comprehensive analysis of threshold dynamics associated with the proposed model.Specifically,the global stability of the disease-free and positive steady states is demonstrated by employing Lyapunov functionals.Lastly,the effects of the vaccination with M72/AS01_(E)and contaminated environments on TB control are numerically simulated.Experimental results indicate that high concentrations of Mycobacterium tuberculosis in contaminated environments may somewhat impede TB control efforts,but that large-scale deployment of new vaccine could significantly reduce the prevalence of TB.展开更多
Detection and treatment of drug resistance in extrapulmonary tuberculosis(EPTB)is a major challenge worldwide.Drug resistance in EPTB has not been studied extensively.However,patients with drug-resistant EPTB have bee...Detection and treatment of drug resistance in extrapulmonary tuberculosis(EPTB)is a major challenge worldwide.Drug resistance in EPTB has not been studied extensively.However,patients with drug-resistant EPTB have been reported to have poor outcomes[1].Rifampicin and isoniazid are the cornerstone drugs in the management of EPTB.Resistance in Mycobacterium(M.)tuberculosis to these drugs commonly arises due to mutations in the‘rpoB’gene and‘katG&inhA’genes,which confer resistance to rifampicin and isoniazid,respectively.Treatment outcomes are affected by the presence of these mutations.In addition,anatomical and physiological barriers impede the effective delivery of drugs to the affected extrapulmonary site[1].An analysis of the frequency of mutations in drug resistant M.tuberculosis strains causing EPTB in our region can help identify patterns of drug resistance.This,in turn,can provide inputs that may be used for modifying standard treatment regimens to make them more effective.The present study aims to identify the frequency and pattern of mutations in the‘rpoB’gene and‘katG&inhA’genes in M.tuberculosis strains isolated from EPTB samples.展开更多
Tuberculosis(TB)remains a critical global health challenge,with 10.8 million new cases and over 1.25 million deaths reported annually,disproportionately affecting low-income regions.Despite its use,the Bacillus Calmet...Tuberculosis(TB)remains a critical global health challenge,with 10.8 million new cases and over 1.25 million deaths reported annually,disproportionately affecting low-income regions.Despite its use,the Bacillus Calmette-Guérin(BCG)vaccine provides limited protection against adult pulmonary TB,necessitating novel solutions.The messenger RNA(mRNA)vaccine technology,proven effective in combating coronavirus disease 2019,offers significant promise for TB prevention.These vaccines elicit robust immune responses by encoding antigens that stimulate humoral and cell-mediated immunity,essential for combating mycobacterium TB.Unlike traditional methods,mRNA vaccines are highly adaptable,scalable,and capable of targeting emerging strains.Preclinical studies highlight the enhanced efficacy of mRNA TB vaccines over BCG,demonstrating their ability to reduce bacterial burdens and generate memory T-cell responses critical for long-term protection.However,challenges persist,including mRNA instability,cold-chain storage needs,and mycobacterium’s complex immune evasion strategies.Innovative solutions,such as lipid nanoparticle delivery systems and selfamplifying mRNA platforms,are being developed to address these barriers.The initiation of clinical trials,notably BioNTech’s BNT164,marks a pivotal advancement in TB vaccine development.These trials focus on safety,immuno genicity,and efficacy,particularly in regions with high TB prevalence.While logistical and financial hurdles remain,mRNA vaccines hold transformative potential to bridge critical gaps in TB prevention.Their adaptability extends to tackling co-infections like human immunodeficiency virus,further amplifying their impact on global health.By integrating mRNA vaccines into existing TB control strategies,these advancements could revolutionize prevention efforts,especially in regions where current solutions fall short.Continued innovation and investment are crucial to harnessing the full potential of mRNA vaccines,positioning them as a cornerstone in the fight against TB and its global eradication.展开更多
BACKGROUND Occult intraocular foreign bodies(IOFBs)can present with atypical symptoms and clinical signs,making diagnosis challenging.We describe a case of an undetected IOFB that was missed on both computed tomograph...BACKGROUND Occult intraocular foreign bodies(IOFBs)can present with atypical symptoms and clinical signs,making diagnosis challenging.We describe a case of an undetected IOFB that was missed on both computed tomography and B-ultrasound,ulti-mately leading to ocular siderosis and secondary glaucoma.CASE SUMMARY A 55-year-old male patient presented to our clinic reporting a one-month history of right ocular discomfort and progressive visual deterioration.The patient had previously received a glaucoma diagnosis at a local healthcare facility.His ocular history included blunt trauma to the affected eye five years prior to presentation.Slit-lamp examination revealed corneal and iris lesions in the right eye.Pupillary dilation facilitated the identification of traumatic lens opacities.Diagnostic imaging modalities,including B-scan ultrasonography and computed tomo-graphy,showed no evidence of retained intraocular foreign material.The patient subsequently underwent uncomplicated pars plana vitrectomy,during which the occult foreign body was successfully extracted.The procedure was completed without intraoperative or immediate postoperative complications.CONCLUSION Awareness of IOFBs in individuals who work in high-risk occupations and prompt referral to a retinal surgeon are very important.展开更多
文摘Tuberculosis(TB)is an airborne infection caused by Mycobacterium tuberculosis that usually affects the lungs.Timely treatment of active TB,diagnosis and prevention of latent TB are very important.However,extrapulmonary TB affects almost any tissues around the eye and orbit,and it then requires a high degree of suspicion to accurately diagnose.Diagnostic delays are common and may lead to morbidity.For ophthalmologists and infectious disease specialists,it is important to work together to accurately diagnose and treat ocular tuberculosis(OTB)to prevent vision loss.This review reports the latest advanced diagnostic methods for active TB and latent TB as well as various known manifestations of 0TB.Important elements of diagnosis and treatment are also reviewed.
基金Supported by National Natural Science Foundation of China (No.81800867)
文摘Experts lack knowledge of periocular tuberculosis（TB） in China. Nested polymerase chain reaction（PCR） shows advantages in diagnosis of extrapulmonary TB. Our study aims to explore the clinical and laboratory features of PCR-confirmed periocular TB. We retrospectively reviewed medical records of presumptive periocular TB and performed nested PCR test to confirm diagnosis. Nine cases were recruited. Clinical symptoms were chronic and insidious. Eight cases achieved favorable visual acuity, while one underwent enucleation due to fungalTB panophthalmitis. Sensitivity of caseous necrosis, acidfast bacilli（AFB） staining and interferon γ release assay（T-SPOT） test are 33.3%, 44.4% and 85.7% respectively. Low lymphocyte percentage（P=0.019） and high monocytelymphocyte ratio（P=0.042） positively correlate with AFB staining. Male gender（P=0.048） and Langhans giant cell（P=0.048） positively correlate with caseous necrosis. To conclude, traditional TB ancillary tests are not as sensitive as nested PCR technique. Several factors facilitate diagnosis including male gender, decreased lymphocytes, and typical Langhans giant cells.
文摘Aim: To study the frequency of various ocular manifestations in diagnosed cases of active pulmonary and extra pulmonary tuberculosis in two different major hospitals in Nepal. Method: A hospital based, cross sectional descriptive study was conducted in the National Tuberculosis Centre, Bhaktapur and BP Koirala Lions Center for Ophthalmic Studies (BPKLCOS), Tribhuvan University Teaching Hospital (TUTH), Kathmandu, Nepal during a period of 18 months from February 2010 to August 2011. Diagnosed cases of systemic tuberculosis were evaluated by ophthalmologists for any ophthalmic manifestations. Results: There were 585 cases in the study. 399 (68%) were cases of pulmonary tuberculosis and 186 (32%) were that of extra pulmonary tuberculosis. Ocular manifestations were seen in 2.6% (15 patients) of the study population;1.25% (6 patients) in cases of pulmonary tuberculosis and 5.37% (9 patients) in extra pulmonary tuberculosis cases. Uveitis (40%) followed by papilloedema (33%) were the two most common ocular manifestations. Of the 25 affected eyes of 15 patients, 2 eyes of patients with choroiditis involving the macular area were legally blind. Majority of the affected cases (67%) had bilateral involvement. Conclusion: Ocular manifestations in tuberculosis vary greatly ranging from mild episcleritis to potentially blinding posterior uveitis, clinical acumen being of great importance in timely diagnosis and treatment so that vision threatening complications can be prevented. Ocular manifestations are more common in extra pulmonary tuberculosis cases.
基金Southwest Hospital Boqing Innovation Fund,Grant/Award Number:2024BQCXJJ-9Fundings for Young Investigators of PLA,Grant/Award Number:2022-JCJQ-QT-004+3 种基金NSFC Key Projects of the Regional Innovation and Development Joint Fund,Grant/Award Number:U23A20413China Postdoctoral Science Foundation,Grant/Award Number:2023M744280National Natural Science Foundation of China,Grant/Award Number:82103778,82172449 and 82172489Southwest Hospital Postdoctoral Starting Fund,Grant/Award Number:5175ZA36BP。
文摘Background:Skeletal tuberculosis(TB)remains a persistent clinical and research chal-lenge due to its chronic course,osteolytic destruction,and the limitations of existing animal models,which often require high-level biosafety containment or fail to repli-cate human skeletal pathology.Methods:This study developed a biosafe,accessible,and versatile murine model of skeletal TB using Mycobacterium smegmatis,a fast-growing,nonpathogenic myco-bacterial species with high genomic homology to Mycobacterium tuberculosis.Three infection routes-subperiosteal calvarial injection,intratibial injection,and intra-cardiac inoculation-were systematically evaluated for their ability to induce lo-calized versus disseminated bone infection under standard biosafety level(BSL)-1 conditions.Results:Subperiosteal calvarial and intratibial injection of M.smegmatis induced local-ized bone lesions characterized by osteolysis,sequestrum formation,granulomatous inflammation,and increased osteoclast activity.Intratibial infection additionally trig-gered compartment-specific immune responses,including neutrophil and macrophage expansion,transient B-cell depletion,and activation of interferon-γ^(+)(IFN-γ^(+))T cells,reflecting active immune remodeling at the infection site.Systemic dissemination via intracardiac injection reproducibly generated progressive vertebral and tibial bone destruction with organized granuloma formation and immune cell infiltration but without prominent sequestrum formation.Compared to intratibial infection,intracar-diac delivery exhibited lower intragroup variability and more closely recapitulated the diffuse progression of extrapulmonary skeletal tuberculosis.Conclusions:This M.smegmatis-based murine model provides a straightforward,reliable,and immunopathologically relevant platform for exploring host-pathogen dynamics,immune-driven bone destruction,and early-stage therapeutic testing in skeletal TB,all within standard BSL-1 laboratories.This model fills a critical gap by enabling BSL-1 research into skeletal TB mechanisms and drug development.
基金Supported by Russian Science Foundation Grant,No.24-15-00185.
文摘BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complete bone regeneration often remains unachieved,contributing to subsequent orthopedic complications.AIM To investigate the efficacy and safety of pamidronate in promoting bone regeneration following surgical treatment of experimental animal tuberculous osteitis.METHODS A controlled randomized basic study of rabbit femoral tuberculosis induced by Mycobacterium tuberculosis strain H37Rv included surgical removal of infected tissue and implantation of osteoinductive bone grafts with the following animal allocation to one of three groups:(1)Bisphosphonates alone;(2)Bisphosphonates combined with anti-tuberculous therapy;and(3)Anti-tuberculous therapy alone.The control group consisted of animals that received no surgical or medical treatment.Clinical evaluations,biochemical markers,micro-computed tomography imaging,and histomorphometry analyses were conducted at 3 months and 6 months postoperatively.RESULTS Pamidronate treatment significantly reduced early implant resorption,increased osteoblastic activity,improved trabecular bone regeneration,and maintained graft integrity compared to the anti-tuberculous therapy-only group.Histologically,pamidronate led to enhanced vascular remodeling and increased bone matrix formation.Crucially,bisphosphonate therapy demonstrated safety,compatibility with anti-tuberculous medications,and did not exacerbate tuberculous inflammation.Furthermore,micro-computed tomography analysis revealed a significant increase in trabecular thickness and density in pamidronate-treated groups,underscoring the anabolic effects of bisphosphonates.Morphometric evaluation confirmed a marked reduction in osteoclast number and activity at graft interfaces.These combined radiological,histological,and biochemical data collectively demonstrate the efficacy of pamidronate as an adjunctive agent in enhancing bone repair outcomes following surgical intervention for tuberculous osteitis.CONCLUSION A single intravenous dose of pamidronate significantly enhances bone regeneration and prevents implant resorption following surgical treatment of tuberculous osteitis.The following prospective studies are needed.
基金supported by the National Natural Science Foundation of China(82574173,82003516)Jiangsu Provincial Natural Science Foundation(BK20251958)+2 种基金Jiangsu Provincial Medical Key Discipline(ZDXK202250)Top Talent Awards Project Fund(RDF-TP-0023,RDF-TP-0030)Postgraduate Research Fund(PGRS2112022)at Xi'an Jiaotong-Liverpool University.
文摘Tuberculosis(TB),one of the oldest infectious diseases caused by Mycobacterium tuberculosis,poses a considerable challenge to global public health.There are approximately 10 million new TB cases worldwide annually,and TB claims the lives of nearly 3 million people each year,making it one of the leading causes of death from a single infectious disease[1].China ranks third globally in terms of TB burden,with approximately 733,000 TB cases reported in 2023[2].Based on the ecological model of health determinants developed by Whitehead and Dahlgren,health determinants can be classified into direct causes.
文摘AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided into four equal groups(n=6/group)as follows:healthy group(HG),ATP-only group(ATPG),sildenafil-onlygroup(SILG),and ATP+sildenafil group(ATP+SLD).ATPG andATP+SLD groups were injected intraperitoneally with ATP(4 mg/kg),while SILG and HG groups were injected withsaline(0.9%NaCl)by the same route as a solvent.One hourafter the administration of ATP and solvent,sildenafil(10 m g/k g)was administered orally to the SILG andATP+SLD groups.This procedure was repeated once a dayfor 4wk.The animals were then sacrificed,eyeballs wereremoved and oxidant and antioxidant parameters weremeasured biochemically.Additionally,the ocular tissueswere evaluated histopathologically.RESULTS:Sildenafil increased oxidant(malondialdehyde)levels and decreased antioxidant levels(total glutathione,superoxide dismutase,catalase)in rat ocular tissues andcaused severe oxidative stress.In addition,sildenafil hasbeen shown histopathologically to cause oxidative damagein retinal layers.ATP treatment suppressed oxidative stressand attenuated histopathological damage in the retinal layers.CONCLUSION:ATP protects retinal tissue againstsildenafil-induced ocular oxidative damage in rats andmay contribute to the development of novel approaches toprevent or treat this damage.
文摘Liver transplantation is a life-saving procedure for patients with end-stage liver diseases and acute liver failure.With advances in surgical techniques and immunosuppressive regimens,patient survival rates have significantly improved.While the systemic complications of post-transplantation are well recognized,ophthalmic manifestations remain underreported.Ophthalmic complications can significantly impair visual function and increase morbidity in these patients.Prolonged immunosuppression makes the patients susceptible to the opportunistic pathogens such as Cytomegalovirus,Candida,Aspergillus,etc.Other common findings include dry eye disease,cataracts and retinal vascular complications which further contribute to the long-term morbidity in these patients.Early ophthalmic evaluation and prompt management are essential to prevent irreversible vision loss and improve post-transplant outcomes.High index of suspicion and multidisciplinary approach is essential to facilitate early diagnosis and treatment.This review highlights the range of ophthalmic complications observed in liver transplant recipients and underscores the need for future research focused on understanding the underlying pathophysiological mechanisms and refining the prophylactic protocols to improve outcomes in this unique patient population.
文摘BACKGROUND Dry eye disease(DED)is a multifactorial ocular surface disorder with rising prevalence.It is closely related to systemic health and psychological factors,such as sleep and mood disorders,which significantly impact the quality of life of patients.AIM To explore the correlations between ocular surface function,sleep quality,and anxiety/depression in patients with DED.METHODS This was a cross-sectional investigative study that included 358 patients with DED between January 2022 and January 2025.Ocular surface was assessed using the ocular surface disease index(OSDI),tear film break-up time,fluorescein staining score,and Schirmer I test.The Pittsburgh Sleep Quality Index(PSQI),Self-Rating Anxiety Scale(SAS),and Self-Rating Depression Scale(SDS)were used to evaluate sleep quality and anxiety/depression levels.Correlation and linear regression analyses were used to explore the relationships.RESULTS The mean PSQI score of the patients was 9.94±2.18;the mean SAS score was 47.30±4.90,and the mean SDS score was 50.08±5.52.These suggested a prevalence of sleep and psychological abnormalities.There was a significant correlation between the indicators of ocular surface function(OSDI,tear film break-up time,fluorescein staining,and Schirmer I test)and PSQI,SAS,and SDS scores(P<0.05).Moreover,multiple regression revealed that age≥50 years(β=1.55,P=0.029),PSQI scores(β=0.58,P<0.001),SAS scores(β=0.17,P=0.017),and SDS scores(β=0.15,P=0.019)were independent predictors of the OSDI scores.CONCLUSION Ocular surface function in patients with DED is closely related to sleep quality and anxiety/depression,emphasizing the need for holistic clinical management.
基金supported by the CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-038 and 2023-I2M-2-001)the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2019PT310029 and 2023-PT310-04).
文摘Tuberculosis(TB)continues to pose a significant threat to global public health,necessitating rapid and precise diagnostic methods and comprehensive detection of antimicrobial resistance(AMR)to facilitate timely clinical management.Traditional diagnostic techniques suffer from extended turnaround times and limited ability to comprehensively profile AMR,often resulting in delayed therapeutic interventions.Highthroughput sequencing(HTS)technologies have revolutionized pathogen research by significantly improving diagnostic speed and accuracy.In the context of TB,diverse sequencing strategies and platforms are being employed to fulfill specific research goals,ranging from elucidating the molecular mechanisms underlying AMR to characterizing the genomic diversity among clinical isolates.This review systematically examines current progress in the application of HTS for rapid pathogen identification,comprehensive AMR profiling,epidemiological studies,advances in novel drugs,and vaccine development.Furthermore,we address existing technological limitations and bioinformatics challenges and explore the future directions necessary for effectively integrating HTS-based methodologies into global TB control efforts.
文摘This report presents a forensic evaluation of a case involving blindness(visual acuity grade 5)following a bee/wasp sting to the left eye.Through systematic analysis of the patient’s multiple hospital admissions,postoperative follow-up data,and a review of the pathological mechanisms of ocular injury caused by bee venom,this study comprehensively assesses the injury characteristics,treatment course,and visual outcomes.Bee venom induces severe complications such as corneal damage,uveitis,cataract,and secondary glaucoma through multiple mechanisms including direct cytotoxicity,immune-inflammatory responses,and enzymatic hydrolysis.Despite interventions including anterior chamber irrigation,phacoemulsification with intraocular lens implantation,and antiglaucoma surgery,the affected eye ultimately lost light perception.Forensic examination confirmed the absence of light perception in the left eye and abnormal visual pathway function,consistent with clinical observations.According to the relevant Chinese disability assessment standard(JR/T 0083-2013,Article 4.2.2),the injury was classified as grade 7 disability.This study provides an in-depth discussion of the mechanisms and key forensic identification points in bee-sting-induced blindness,offering a scientific reference for similar forensic clinical cases.
基金funded by the National Key Research and Development Program of China(grant number 2022YFC2305204).
文摘Objective To determine the proportions of drug-resistant tuberculosis(TB),its trends,and the drug resistance-conferring mutations among patients with pulmonary TB aged 10-24 years in China.Methods The data of patients with pulmonary TB were retrieved from a national drug-resistant TB survey for analysis.Joinpoint regression software was used to analyze time trends.We also used whole genome sequencing to analyze the lineages and drug resistance-conferring mutations of 621 isolates.Results Among 4,235 patients with pulmonary TB,the proportion of new cases of multidrug-resistant tuberculosis(MDR-TB)was 3.18%(95%confidence interval[CI]:2.37-4.15)for adolescents and 3.76%(95%CI:3.03-4.60)for young adults;for previously treated patients,MDR-TB accounted for 11.25%(95%CI:5.28-20.28)of adolescents and 11.05%(95%CI:6.88-16.55)of young adults.The proportion of patients with MDR-TB remained stable among both new and previously treated patients aged 10-24 years during the study period.Through whole genome sequencing,we found that the most common mutations in the MDR-TB strains were Ser315Thr in the katG gene(71.74%)and Ser450Leu in the rpoB gene(50.00%).Conclusion This study revealed a high proportion of MDR-TB among adolescents and young adults,indicating that urgent and comprehensive measures are needed to reduce the emergence and transmission of drug-resistant TB among this population in China.
基金Supported by Vision International Eye Missions-USA,“One Drop for All”,Italy,and Private Donors in the Netherlands.
文摘AIM:To ascertain the pattern of ocular morbidity in a population of primary school children in rural Kenya as it is a prerequisite for planning effective preventive and therapeutic strategies.METHODS:A cross-sectional survey of ocular symptoms and clinical eye examinations were performed in a sample of 35 rural primary schools in the semi-arid region of Kajiado West sub-county in S.W.Kenya,amongst a seminomadic tribe(Maasai).Students in Grades 1-8 were included.Visual acuity was measured using the Snellen“tumbling E”chart at 6 m.Children with symptoms of refractive error underwent non-cycloplegic refraction.RESULTS:A total of 2036 children(1084 males)between the ages of 4-20y were examined.Conjunctival actinic changes were present in 22%(442/2036).Nine cases were seen with a potential squamous carcinoma.No overt classical ocular signs of vitamin A deficiency were noted,although 181(8.9%)children complained of nyctalopia.Three hundred thirty-six(16.5%)children had a visual acuity worse than 6/12 in either eye,were unable to read N10 near text at 40 cm or had symptoms suggestive of refractive error.Refractive data led to an estimate of hyperopia of+1.00 D or more in 3.9%and of myopia of-0.50 D or more in either eye in 3.0%of the study population.CONCLUSION:Solar exposure-and dust-related conjunctival pathology is common.As this may develop into potentially sight-or even life-threatening conditions,it warrants further study,and preventive strategies may be needed.Complaints of nyctalopia were common and could suggest vitamin A deficiency.The prevalence of refractive errors is low in this rural African population.
基金supported by the National Science and Technology Major Project for the Prevention and Control of Emerging and Major Infectious Diseases[2025ZD01908702]Peking University Medicine Fund of Fostering Young Scholars’Scientific&Technological innovation[BMU2024YFJHP014]supported by Fundamental Research Funds for the Central Universities+1 种基金Key Clinical Projects of Peking University Third Hospital[BYSYZD2022014]Peking University Third Hospital[2025024].
文摘Objective Post tuberculosis lung disease(PTLD)manifests in various forms,including tuberculosisassociated chronic obstructive pulmonary disease(TB-COPD),yet the clinical features of PTLD remain undercharacterized.This study aimed to assess longitudinal changes in lung function over a 5-year period and to identify predictors of airflow obstruction in a cohort of patients treated for active pulmonary TB.Methods Patients with active pulmonary TB were enrolled in this study and were followed during treatment,at treatment completion and five years post-treatment.Assessments included lung function and chest CT,analyzing longitudinal trends and airflow obstruction risk factors.Results Among 53 patients(mean age 36.9±13.9 years;64.2%male),7 patients(13.2%)exhibited airflow obstruction.At the 5-year follow-up,the mean FEV_(1)/FVC declined significantly(76.27%±12.04%vs.80.23%±11.02%,P<0.001)and 9 patients(17.0%)exhibited airflow obstruction.Seven of these patients predominantly showed air trapping consistent with small airway disease on chest CT,aligning with TB-COPD phenotype.Notably,four young-to-middle-aged patients(<60 years old)had persistent obstruction over the five years.Conclusion The initial test revealed that 13.2%of patients presented with airflow obstruction.By the 5-year follow-up,this proportion had increased to 17.0%,with most cases demonstrating imaging findings aligning with TB-COPD,even among younger,non-smoking individuals.These findings emphasize the importance of long-term follow-up and routine lung function assessments in TB survivors.
基金supported by the National Natural Science Foundation of China,No.82271115(to MY).
文摘Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglion cells and their axons,leading to axonal transport dysfuntion,subsequently causing secondary damage to anterior or posterior ends of the visual system.Accordingly,recent evidence indicates that glaucoma is a degenerative disease of the central nervous system that causes damage throughout the visual pathway.However,the effects of glaucoma on synaptic plasticity in the primary visual cortex remain unclear.In this study,we established a mouse model of unilateral chronic ocular hypertension by injecting magnetic microbeads into the anterior chamber of one eye.We found that,after 4 weeks of chronic ocular hypertension,the neuronal somas were smaller in the superior colliculus and lateral geniculate body regions of the brain contralateral to the affected eye.This was accompanied by glial cell activation and increased expression of inflammatory factors.After 8 weeks of ocular hypertension,we observed a reduction in the number of excitatory and inhibitory synapses,dendritic spines,and activation of glial cells in the primary visual cortex contralateral to the affected eye.These findings suggest that glaucoma not only directly damages the retina but also induces alterations in synapses and dendritic spines in the primary visual cortex,providing new insights into the pathogenesis of glaucoma.
基金Supported by the Faculty of Medicine,Prince of Songkla University.Wainipitapong S has received grants from the Faculty of Medicine,Prince of Songkla University。
文摘AIM:To investigate the clinical characteristics and treatment outcomes,including visual function and overall survival(OS)of patients with ocular adnexal diffuse large B-cell lymphoma(OA-DLBCL).METHODS:This retrospective cohort study enrolled 29 patients diagnosed with OA-DLBCL based on histopathological biopsy between 2006 and 2023.Patients were stratified into two subgroups:primary OA-DLBCL(no prior history of lymphoma)and secondary OA-DLBCL(history of DLBCL at non-ocular adnexal sites).OS was defined as the time interval from OA-DLBCL diagnosis to death from any cause.Survival analysis was performed using the Kaplan–Meier method,and prognostic factors affecting OS were identified using multivariate Cox proportional hazards regression with a stepwise selection approach.RESULTS:The cohort included 24 patients with primary OA-DLBCL(13 males,11 females;mean age:61.36±18.29y)and 5 patients with secondary OA-DLBCL(2 males,3 females;mean age:50.94±18.17y).Among the primary OA-DLBCL subgroup,12 patients(50%)presented with advanced disease(Ann Arbor stage IIIE–IV),and 16 patients(66%)were classified as T4 disease according to the tumor-node-metastasis(TNM)staging system.The mean final visual acuity was 1.72±1.10 in the primary group and 0.90±1.18 in the secondary group.The 5-year OS rate for the entire cohort was 27.7%.Multivariate analysis identified five factors significantly associated with poor survival outcomes:epiphora[adjusted hazard ratio(aHR),36.95],atherosclerotic cardiovascular disease(aHR,10.08),human immunodeficiency virus(HIV)infection(aHR,12.47),M1 stage(aHR,6.99),and secondary OA-DLBCL(aHR,6.03;all P<0.05).The median OS was 1.68y for primary OA-DLBCL and 1.12y for secondary OA-DLBCL.CONCLUSION:A substantial proportion of patients with primary OA-DLBCL present with advanced-stage disease at diagnosis.Epiphora,atherosclerotic cardiovascular disease,HIV infection,M1 stage,and secondary OA-DLBCL are independent prognostic factors for poor survival outcomes.These findings emphasize the urgent need for optimized therapeutic strategies and early screening protocols to improve the management of OA-DLBCL,particularly in developing countries.
文摘To assess the effectiveness of vaccination in contaminated environments,this study introduces a modeling framework that encompasses two transmission routes,namely direct human-to-human contact and indirect human-to-environment contact,as well as the implementation of new M72/AS01_(E)vaccine.Motivated by this,a coupled age-structured tuberculosis(TB)model is proposed.Its well-posedness requirement is verified using the integrated semigroup theory.Furthermore,this study presents a comprehensive analysis of threshold dynamics associated with the proposed model.Specifically,the global stability of the disease-free and positive steady states is demonstrated by employing Lyapunov functionals.Lastly,the effects of the vaccination with M72/AS01_(E)and contaminated environments on TB control are numerically simulated.Experimental results indicate that high concentrations of Mycobacterium tuberculosis in contaminated environments may somewhat impede TB control efforts,but that large-scale deployment of new vaccine could significantly reduce the prevalence of TB.
文摘Detection and treatment of drug resistance in extrapulmonary tuberculosis(EPTB)is a major challenge worldwide.Drug resistance in EPTB has not been studied extensively.However,patients with drug-resistant EPTB have been reported to have poor outcomes[1].Rifampicin and isoniazid are the cornerstone drugs in the management of EPTB.Resistance in Mycobacterium(M.)tuberculosis to these drugs commonly arises due to mutations in the‘rpoB’gene and‘katG&inhA’genes,which confer resistance to rifampicin and isoniazid,respectively.Treatment outcomes are affected by the presence of these mutations.In addition,anatomical and physiological barriers impede the effective delivery of drugs to the affected extrapulmonary site[1].An analysis of the frequency of mutations in drug resistant M.tuberculosis strains causing EPTB in our region can help identify patterns of drug resistance.This,in turn,can provide inputs that may be used for modifying standard treatment regimens to make them more effective.The present study aims to identify the frequency and pattern of mutations in the‘rpoB’gene and‘katG&inhA’genes in M.tuberculosis strains isolated from EPTB samples.
文摘Tuberculosis(TB)remains a critical global health challenge,with 10.8 million new cases and over 1.25 million deaths reported annually,disproportionately affecting low-income regions.Despite its use,the Bacillus Calmette-Guérin(BCG)vaccine provides limited protection against adult pulmonary TB,necessitating novel solutions.The messenger RNA(mRNA)vaccine technology,proven effective in combating coronavirus disease 2019,offers significant promise for TB prevention.These vaccines elicit robust immune responses by encoding antigens that stimulate humoral and cell-mediated immunity,essential for combating mycobacterium TB.Unlike traditional methods,mRNA vaccines are highly adaptable,scalable,and capable of targeting emerging strains.Preclinical studies highlight the enhanced efficacy of mRNA TB vaccines over BCG,demonstrating their ability to reduce bacterial burdens and generate memory T-cell responses critical for long-term protection.However,challenges persist,including mRNA instability,cold-chain storage needs,and mycobacterium’s complex immune evasion strategies.Innovative solutions,such as lipid nanoparticle delivery systems and selfamplifying mRNA platforms,are being developed to address these barriers.The initiation of clinical trials,notably BioNTech’s BNT164,marks a pivotal advancement in TB vaccine development.These trials focus on safety,immuno genicity,and efficacy,particularly in regions with high TB prevalence.While logistical and financial hurdles remain,mRNA vaccines hold transformative potential to bridge critical gaps in TB prevention.Their adaptability extends to tackling co-infections like human immunodeficiency virus,further amplifying their impact on global health.By integrating mRNA vaccines into existing TB control strategies,these advancements could revolutionize prevention efforts,especially in regions where current solutions fall short.Continued innovation and investment are crucial to harnessing the full potential of mRNA vaccines,positioning them as a cornerstone in the fight against TB and its global eradication.
基金Supported by The Tianjin Health Research Project,No.ZC20069the Foundation of the Committee of Integrated Traditional Chinese and Western Medicine,No.2021011the Science and Technology Foundation of Tianjin Eye Hospital,No.YKYB1901.
文摘BACKGROUND Occult intraocular foreign bodies(IOFBs)can present with atypical symptoms and clinical signs,making diagnosis challenging.We describe a case of an undetected IOFB that was missed on both computed tomography and B-ultrasound,ulti-mately leading to ocular siderosis and secondary glaucoma.CASE SUMMARY A 55-year-old male patient presented to our clinic reporting a one-month history of right ocular discomfort and progressive visual deterioration.The patient had previously received a glaucoma diagnosis at a local healthcare facility.His ocular history included blunt trauma to the affected eye five years prior to presentation.Slit-lamp examination revealed corneal and iris lesions in the right eye.Pupillary dilation facilitated the identification of traumatic lens opacities.Diagnostic imaging modalities,including B-scan ultrasonography and computed tomo-graphy,showed no evidence of retained intraocular foreign material.The patient subsequently underwent uncomplicated pars plana vitrectomy,during which the occult foreign body was successfully extracted.The procedure was completed without intraoperative or immediate postoperative complications.CONCLUSION Awareness of IOFBs in individuals who work in high-risk occupations and prompt referral to a retinal surgeon are very important.
