Exosomas como tratamiento alternativo del síndrome genitourinario de la menopausia / Exosomes as an alternative treatment for genitourinary syndrome of menopause

Objetivo: Evaluar el efecto de los exosomas como tratamiento alternativo en la restauración del síndrome genitourinario de la menopausia en pacientes que acuden a una consulta ginecológica, en Valencia, Estado Carabobo, en el período junio - agosto de 2023. Métodos: Estudio prospectivo, descriptivo, exploratorio, incluyó tres casos de mujeres con diagnóstico de síndrome genitourinario de la menopausia. Se evaluó la respuesta en cuanto a los síntomas, examen clínico según el índice de salud vaginal, la satisfacción con el tratamiento y la tolerabilidad. Se aplicó el tratamiento con exosomas: 2 cc con técnica de punto a punto en todas las paredes vaginales y 1 cc en el vestíbulo, en 3 sesiones, con intervalo de 15 días. Resultados: La edad de las pacientes estuvo entre 53 y 56 años, con un promedio de tiempo de menopausia de 6,6 años. Previo al tratamiento, había un nivel alto de irritación vaginal (100 %), dolor en el introito (100 %), sequedad vaginal, dispareunia, hipersensibilidad y las no relaciones sexuales (66,67 %). Postratamiento predominó la ausencia de los síntomas: sequedad vaginal, dispareunia, hipersensibilidad y dolor en introito (100 %); irritación vaginal y no relaciones sexuales (66,67 %) (p = 0,0001). La mediana del índice de salud vaginal previa fue 13 (10 ­ 13) y posterior fue 18 (17 ­ 20) (p = 0,0476). La satisfacción y tolerabilidad fue de 66,67 %. Una paciente refirió dolor leve. Conclusión: La terapia con exosomas es eficaz para reducir los síntomas y signos del síndrome genitourinario de la menopausia, y bien tolerado(AU)

Objective: To evaluate the effect of exosomes as an alternative treatment in the restoration of genitourinary syndrome of menopause in patients attending a gynecological consultation in Valencia, Carabobo State, in the period June - August 2023. Methods: A prospective, descriptive, exploratory study included three cases of women diagnosed with genitourinary syndrome of menopause. Response was assessed in terms of symptoms, clinical examination according to vaginal health index, satisfaction with treatment and tolerability. Treatment with exosomes was applied: 2 cc with point-to-point technique on all vaginal walls and 1 cc in the vestibule, in 3 sessions, with an interval of 15 days. Results: The age of the patients was between 53 and 56 years, with a mean menopause time of 6.6 years. Prior to treatment, there was a high level of vaginal irritation (100%), pain in the introitus (100%), vaginal dryness, dyspareunia, hypersensitivity and non-sexual intercourse (66.67%). Post-treatment, the absence of symptoms predominated: vaginal dryness, dyspareunia, hypersensitivity and pain in the introitus (100%); vaginal irritation and no sexual intercourse (66.67%) (p = 0.0001). The median index of previous vaginal health was 13 (10 ­ 13) and subsequent was 18 (17 ­ 20) (p = 0.0476). Satisfaction and tolerability was 66.67%. One patient reported mild pain. Conclusion: Exosome therapy is effective in reducing the symptoms and signs of genitourinary syndrome of menopause, and well tolerated(AU)

Cuidados respiratorios en pacientes con atrofia muscular espinal para evitar el fallo ventilatorio agudo y la traqueostomía: revisión literaria y recomendaciones consensuadas / Respiratory care in patients with spinal muscular atrophy to avoid acute ventilatory failure and tracheostomy: literature review and consensus recommendations

La atrofia muscular espinal (AME) 5q es una de las enfermedades neuromusculares de mayor incidencia en la infancia. Sin embargo, la prevalencia de AME tipo 1, su forma más severa de presentación, es menor debido a muertes prematuras evitables antes de los dos años por insuficiencia ventilatoria subtratada. La irrupción de nuevos tratamientos modificadores de la enfermedad pueden cambiar dramáticamente este pronóstico y es una oportunidad para actualizar el manejo respiratorio, a través de cuidados estandarizados básicos, preferentemente no invasivos, abordando la debilidad de los músculos respiratorios, la insuficiencia tusígena y ventilatoria, con un enfoque preventivo. La siguiente revisión literaria entrega estrategias para evitar la intubación y la traqueostomía usando soporte ventilatorio no invasivo (SVN), reclutamiento de volumen pulmonar (RVP) y facilitación de la tos. Se analizan en detalle los protocolos de extubación en niños con AME tipo 1.

Spinal muscular atrophy (SMA) 5q is one of the neuromuscular diseases with the highest incidence in childhood. Nevertheless, the prevalence of its most severe form SMA1 is lower due to premature preventable deaths before two years of age related to ventilatory insufficiency undertreated. The emergence of new disease-modifying treatments can dramatically change this prognosis and is an opportunity to update respiratory management, through basic standardized care, mostly non-invasive, addressing respiratory muscles pump weakness, cough and ventilatory insufficiency with a preventive approach. This literature review provides consensus recommendations for strategies to avoid intubation and tracheostomy using noninvasive ventilatory support (NVS), lung volume recruitment (LVR), and cough facilitation. Extubation protocols in children with SMA type 1 are analyzed in detail.

Nuevos paradigmas en atrofia muscular espinal de presentación temprana: siempre es bueno recordar / New paradigms in early-onset spinal muscular atrophy: a reminder is always beneficial

La atrofia muscular espinal (AME) de presentación temprana representa la variante más severa, con una expectativa de vida generalmente no mayor a dos años sin soporte ventilatorio, debido a la insuficiencia respiratoria y la dificultad para toser. Tradicionalmente, el manejo respiratorio en muchos países ha incluido la traqueostomía para proporcionar asistencia ventilatoria invasiva de manera continua. No obstante, la introducción de medicamentos de precisión ha modificado la progresión natural de la enfermedad, evidenciando mejoras significativas en los hitos motores y beneficiando también la función respiratoria. A pesar de estas mejoras, en muchos casos sigue siendo necesaria la ventilación intermitente y/o continua, además de la facilitación de la tos. Estas necesidades pueden abordarse de forma no invasiva mediante el soporte ventilatorio no invasivo (SVN), la in-exsuflación mecánica (IEM) y el reclutamiento de volumen pulmonar (RVP), que son considerados pilares del tratamiento respiratorio en enfermedades neuromusculares. Estas estrategias promueven el desarrollo y mantenimiento de la función respiratoria, reduciendo el riesgo de exacerbaciones respiratorias que podrían llevar a intubaciones evitables. Comúnmente, los pacientes con AME experimentan intentos fallidos de extubación siguiendo protocolos tradicionales, siendo catalogados como no extubables y potenciales candidatos a traqueostomía. No obstante, existen protocolos de extubación específicos para AME que emplean SVN e IEM con un alto porcentaje de éxito, evitando traqueostomías innecesarias que pueden complicar la progresión de la enfermedad y afectar la calidad de vida. El enfoque respiratorio no invasivo es una opción de manejo segura tanto en el hospital como en el hogar, ofreciendo una mejor calidad de vida para los pacientes y sus familias.

Early-onset spinal muscular atrophy (SMA) is the most severe variant, with a life expectancy generally not exceeding two years without ventilatory support due to respiratory insufficiency and difficulty in coughing. Traditionally, respiratory management in many countries has included tracheostomy to provide continuous invasive ventilatory support. However, the introduction of precision medicine has altered the natural progression of the disease, showing significant improvements in motor milestones and also benefiting respiratory function. Despite these improvements, many cases still require intermittent and/or continuous ventilation, as well as cough facilitation. These needs can be addressed non-invasively through non-invasive ventilatory support (NIV), mechanical insufflation-exsufflation (MIE), and lung volume recruitment (LVR), which are considered the pillars of respiratory treatment in neuromuscular diseases. These strategies promote the development and maintenance of respiratory function, reducing the risk of respiratory exacerbations that could lead to avoidable intubations. Commonly, SMA patients experience failed extubation attempts following traditional protocols, being labeled as non-extubatable and potential candidates for tracheostomy. Nevertheless, there are specific extubation protocols for SMA that employ NIV and MIE with a high success rate, avoiding unnecessary tracheostomies that can complicate disease progression and impact quality of life. The non-invasive respiratory approach is a safe management option both in the hospital and at home, offering a better quality of life for patients and their families.

Mining and analysis of ADE signals of two camptothecin topoisomerase 1 inhibitors / 中国药房

OBJECTIVE To mine and analyze the adverse drug events （ADE） signals of two camptothecin topoisomerase 1 inhibitors， i.e. irinotecan and topotecan， and to provide reference for clinical medication safety. METHODS Based on the U.S. Food and Drug Administration Adverse Event Reporting System （FAERS） database， ADE report data for the aforementioned two drugs were extracted from January 1， 2004 to March 31， 2023. After processing the data， signal mining was conducted by using the reporting odds ratio in conjunction with the Bayesian confidence propagation neural network， followed by analysis. RESULTS A total of 14 738 relevant ADE reports were screened， among which 11 483 were associated with irinotecan and 3 255 with topotecan. The ADE reports for irinotecan were predominantly male， whereas for topotecan， they were predominantly female； the age of patients using the two drugs mainly concentrated in 45-＜75 years old. A total of 847 signals were detected， involving 24 system organ classes （SOCs）. Among them， 565 signals of irinotecan were detected， involving 24 SOCs， primarily concentrating on gastrointestinal disorders， general disorders and administration site conditions， blood and lymphatic system disorders； the most frequently reported ADE was diarrhea， and the ADE with the strongest signal intensity was cholinergic syndrome. A total of 282 signals of topotecan were detected， involving 22 SOCs， primarily concentrating on general disorders and administration site conditions， investigations， blood and lymphatic system disorders， and gastrointestinal disorders； the most frequently reported ADEs were death and anemia， and the ADE with the strongest signal intensity was febrile bone marrow aplasia. ADE signals for irinotecan such as metastatic colorectal cancer， peripheral sensory neuropathy， steatohepatitis， and those for topotecan such as iris atrophy， retinal degeneration， vitreous hemorrhage， were not documented in their respective drug instruction. CONCLUSIONS ADEs of irinotecan and topotecan primarily involve the digestive and hematologic systems， warranting close clinical monitoring. Cholinergic syndrome caused by irinotecan should be concerned. In addition， patients receiving irinotecan should also be monitored for ADE such as metastatic colorectal cancer， peripheral sensory neuropathy， steatohepatitis， and proteinuria； for patients using topotecan， enhanced surveillance of ocular diseases is recommended to ensure medication safety.

Advances in the treatment of spinal muscular atrophy / 国际儿科学杂志

Spinal muscular atrophy（SMA），an autosomal recessive genetic disease characterized by progressive weakness and atrophy of the proximal limbs caused by degeneration of motor neurons in the anterior horn of the spinal cord，can affect multiple systems such as respiratory，digestive，and skeletal systems. Untreated children with severe type 1 SMA usually die within 2 years of age. In recent years，the treatment of SMA has developed rapidly，and a variety of drugs have been approved to benefit patients. However，none of the existing therapeutic drugs or regimens can achieve a complete cure. Therefore，the combination of different therapeutic drugs and the research and development of new drugs may be the way forward for the treatment of SMA. The latest progress of therapeutic drugs and combination therapy in SMA are summarized in this review，which may be helpful for guiding the treatment of SMA.

A Pedigree Study of Hereditary Auditory Neuropathy with Optic Atrophy / 听力学及言语疾病杂志

Objective To investigate the genetic causes of auditory neuropathy with optic atrophy in a family.Methods The proband's medical history and family history were inquired in detail,and relevant clinical examina-tions were performed to confirm the diagnosis of auditory neuropathy with optic atrophy,and the genetic pedigree of the family was drawn.Peripheral blood of proband(Ⅲ-7)was collected for whole exome sequencing,and the patho-genicity of the detected mutations were interpreted.Blood samples of proband's wife(Ⅲ-8),eldest daughter(Ⅳ-7),second daughter(Ⅳ-9)and son(Ⅳ-10)were tested for mutation sites by Sanger sequencing.Combined with clinical manifestations and examination results,the family was studied.Results The genetic pattern of this family was autosomal dominant.The proband showed decreased visual acuity at the age of 19,bilateral sensorineural deaf-ness at the age of 30,and decreased speech recognition rate.Among 20 members of the family of 5 generations,10(2 deceased)showed similar symptoms of hearing and visual impairment.Proband(Ⅲ-7),eldest daughter(Ⅳ-7)and son(Ⅳ-10)underwent relevant examination.Pure tone audiometry showed bilateral sensorineural deafness.ABR showed no response bilaterally.The 40 Hz AERP showed no response in both ears.OAE showed responses in some or all of the frequencies.No stapedial reflex was detected.The eye movement of Ⅲ-7 and Ⅳ-10 were reasona-ble in all directions,and color vision was normal.Ocular papilla atrophy was observed in different degrees in fundus examination.OCT showed thinning of optic disc nerve fibers in both eyes,and visual evoked potential showed pro-longed P100 wave peak.They were diagnosed as hereditary auditory neuropathy with optic atrophy.A mutation of the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)at a pathogenic locus on chromosome 3 was detected by whole exon detection in Ⅲ-7.The results of generation sequencing analysis showed that the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)mutation of chromosome 3 was also found in Ⅳ-7 and Ⅳ-10.Meanwhile,the gen-otypes of Ⅲ-8 and Ⅳ-9 were wild homozygous,that is,no mutation occurred.Conclusion The OPA1 c.1334G＞A(p.Arg445His,NM_015560.2)mutation site might be the pathogenic mutation in this family.

Application prospect of mesenchymal stem cells in promoting muscle tissue repair / 中国组织工程研究

BACKGROUND:Mesenchymal stem cells are multipotent stromal cells isolated from bone marrow,fat,umbilical cord and other tissues.It can differentiate into different cell types and secrete a variety of proteins with therapeutic potential,which has a good application prospect in the repair of muscle tissue. OBJECTIVE:To review the research progress of mesenchymal stem cells in promoting muscle tissue repair and provide a theoretical basis for further clinical application. METHODS:Relevant articles published from inception to 2022 were retrieved from CNKI,VIP,WanFang,PubMed,Embase and Web of Science databases.The keywords were"mesenchymal stem cells,muscle tissue,muscle injury,muscle atrophy,exosomes,scaffolds"in Chinese and English.The literature about mesenchymal stem cell migration promoting muscle fiber proliferation and repair was screened.Finally,98 articles were included for review and analysis. RESULTS AND CONCLUSION:(1)The related mechanisms of mesenchymal stem cell migration promoting muscle fiber proliferation and repair are complex,mostly by anti-inflammatory,inhibiting interstitial fibrosis,inhibiting the fat formation and other ways to promote muscle fiber proliferation and repair.(2)The related biological scaffolds and cell co-culture based on mesenchymal stem cells can significantly compensate for the low survival rate of mesenchymal stem cells after colonization.(3)At present,mesenchymal stem cell therapy still has apparent limitations.In the future,mesenchymal stem cells combined with other therapies should become the primary development trend.

Mechanism and potential of vitamin C supplementation in sarcopenia prevention and treatment / 中国组织工程研究

BACKGROUND:Vitamin C,as an essential nutrient,has a wide range of biological effects and a variety of biological functions related to the pathogenesis of sarcopenia.Vitamin C supplementation is expected to be a novel prevention and treatment measure for sarcopenia. OBJECTIVE:To review recent research advances in the application of vitamin C in the pathogenesis and treatment of sarcopenia,and to discuss the potential role of vitamin C in the prevention and treatment of sarcopenia and possible mechanistic pathways based on published evidence. METHODS:The first author performed a computer search of PubMed,Web of Science,CNKI and other databases for relevant studies involving vitamin C in sarcopenia.The search keywords were"vitamin C,ascorbic acid,L-ascorbic acid,ascorbate,antioxidants,oxidative stress,sarcopenia,muscular atrophy,muscle weakness,muscle development,skeletal muscle regenerate,muscles,skeletal muscle"in English and Chinese,respectively.The search period was from each database inception to July 2023.After screening,85 articles were included for further review. RESULTS AND CONCLUSION:Ensuring adequate dietary vitamin C intake or maintaining normal circulating levels of vitamin C will help to reduce age-related muscle loss and decrease the prevalence of sarcopenia.In addition,vitamin C supplementation is also useful for improving skeletal muscle mass,strength and physical function with potential synergistic effects in exercise strategies for sarcopenia.The effects of vitamin C on sarcopenia may be via the following biological mechanisms:vitamin C limits the activation of the ubiquitin-proteasome pathway mainly by inhibiting oxidative stress and inflammatory responses in skeletal muscle,thus positively regulating protein metabolic homeostasis,and may enhance mitochondrial antioxidant defenses through its antioxidant effects to maintain healthy mitochondrial function.In addition,vitamin C affects myoblast proliferation,differentiation and myotube size,mainly by increasing the expression of myogenic regulatory factors and activating protein synthesis signaling pathways,which contribute to the promotion of muscle development as well as the repair and regeneration of damaged muscle tissue.The positive effects of vitamin C in sarcopenia need to be studied in large samples and with optimized designs for important influencing factors,such as the choice of supplementation dose and duration,the design of exercise prescription when vitamin C is combined with an exercise intervention,and the assessment of the redox status of the individual.It is recommended that future studies should be conducted in older patients with sarcopenia(<50 μmol/L)with suboptimal vitamin C status to investigate the efficacy of a combined intervention of long-term supplementation with 1 000 mg/d vitamin C(for 6 months or longer)with at least two or more types of multi-type combined exercise,with supplementation timed to take place at 1 hour after the end of the exercise,and with monitoring of markers of oxidative damage produced during the exercise such as malondialdehyde or protein hydroxyl levels were monitored.In conclusion,the optimal dose and timing of vitamin C supplementation for older adults with sarcopenia needs to be explored more,while the appropriate design of exercise prescriptions(especially the type and intensity of exercise)needs to be further determined.

Effect of ginsenoside Rg1 on muscle degeneration after massive rotator cuff injury in mice / 中国组织工程研究

BACKGROUND:Rotator cuff muscle degeneration(muscle atrophy,fibrosis and fatty infiltration)is a common condition after rotator cuff tears,which seriously affects shoulder function and surgical outcomes.Ginsenoside Rg1 has biological effects such as anti-oxidation,anti-apoptosis and lipid-lowering.However,the effect of ginsenoside Rg1 on muscle degeneration after rotator cuff tear has not been reported. OBJECTIVE:To investigate the effect of ginsenoside Rg1 on muscle degeneration after massive rotator cuff tear in mice. METHODS:Sixty C57BL/6J mice were randomly divided into sham group,model group,ginsenoside Rg1 low dose group and ginsenoside Rg1 high dose group,with 15 mice in each group.The skin of the right shoulder of mice in the sham group was cut and sutured.Massive rotator cuff tear mouse models of the right shoulder were established in the other three groups.Supraspinatus tendon and suprascapular nerve compression were administrated.Mice in the sham and model groups were intraperitoneally injected with 0.5 mL of saline after operation,while those in the ginsenoside Rg1 low and high dose groups were intraperitoneally injected with ginsenoside Rg1 30 and 60 mg/kg respectively,once a day,for 6 weeks.Mice were assessed for limb function by gait analysis the day after the last injection.After euthanasia,the supraspinatus muscle on the operated side was taken to measure the muscle atrophy rate and muscle contractility.Muscle tissue was stained with oil red O and Masson.RT-PCR was used to detect the expression of atrophy,fibrosis,and fatty infiltration related genes. RESULTS AND CONCLUSION:Compared with the model group,low-and high-dose ginsenoside Rg1 significantly increased paw print area and step length(P<0.05).Compared with the model group,low-and high-dose ginsenoside Rg1 significantly increased myofiber cross-sectional area and supraspinatus contractility(P<0.05),and significantly decreased wet muscle mass reduction ratio,fatty infiltration area ratio,and collagen fiber area ratio(P<0.05).Compared with the model group,low-and high-dose ginsenoside Rg1 significantly decreased the expression of atrophy,fibrosis,and fatty infiltration related genes(P<0.05).There was no significant difference in paw print area,supraspinatus muscle contractility,and myofiber cross-sectional area between ginsenoside Rg1 low and high dose groups(P>0.05),and all other indexes were better in the ginsenoside Rg1 high dose group than in the ginsenoside Rg1 low dose group(P<0.05).To conclude,ginsenoside Rg1 could significantly reduce muscle atrophy,fibrosis and fatty infiltration following massive rotator cuff tear in mice,which is beneficial to improve muscle strength and limb function.

Effects of moderate-intensity continuous training and high-intensity interval training on obesity-related muscle atrophy in mice / 中国组织工程研究

BACKGROUND:Obesity has become a global health issue,often accompanied by complications including obesity-related muscle atrophy.While exercise has been reported to improve various obesity-related diseases,there is limited research focusing on exercise modes. OBJECTIVE:To compare the effects of moderate-intensity continuous training(MICT)and high-intensity interval training(HIIT)on obesity-related muscle atrophy in mice under the premise of the same exercise distance,providing a scientific basis for exercise interventions for obesity-related muscle atrophy. METHODS:Seventy-two male C57BL/6 mice were divided into six groups(n=12 per group):standard chow diet,standard chow diet+MICT,standard chow diet+HIIT,high-fat diet,high-fat diet+MICT,and high-fat diet+HIIT.The study evaluated the effects of 8-week treadmill training with different exercise modes on long-term high-fat diet-induced muscle atrophy by detecting muscle mass,muscle index,muscle fiber cross-sectional area,muscle lipid deposition,and the expression of muscle atrophy marker genes Murf-1 and Atrogin-1 in the gastrocnemius muscle of mice exposed to long-term high-fat diet. RESULTS AND CONCLUSION:Compared to the high-fat diet group,both MICT and HIIT improved the decrease in gastrocnemius muscle index(MICT+18.8%vs.HIIT+17.6%,not significant between the two modes),muscle fiber atrophy(MICT+15.5%vs.HIIT+13.7%,not significant between the two modes),and muscle lipid deposition(MICT-19.8%vs.HIIT-17.1%,not significant between the two modes).At the gene level,compared with the high-fat diet group,both MICT and HIIT could significantly down-regulate the expression of Murf-1(MICT-62.4%vs.HIIT-52.6%,the down-regulation caused by MICT was significantly greater than that by HIIT;P＜0.01)and Atrogin-1(MICT-43.3%vs.HIIT-29.8%,the down-regulation caused by MICT was significantly greater than that by HIIT;P＜0.01).Based on exercise mode comfort and genetic evidence,MICT mode might be more suitable for exercise interventions in obesity-related muscle atrophy.

Logistic regression analysis and risk model construction of choroidopathy sec-ondary to high myopia / 眼科新进展

Objective To analyze the influencing factors of choroidopathy(choroidal atrophy and choroidal neovas-cularization)secondary to high myopia based on Logistic regression analysis and to construct a Nomogram risk prediction model based on the related factors,so as to provide guidance for clinical treatment.Methods A total of 340 patients(680 eyes)with high myopia admitted to Beijing Jishuitan Hospital from January 2021 to January 2023 were selected and di-vided into group A(170 patients,340 eyes)and group B(170 patients,340 eyes).The incidence of choroidopathy in the two groups was compared.The groups A and B were divided into two subgroups,subgroup a and subgroup b,according to whether choroidopathy occurred or not.Multivariate Logistic regression analysis was carried out to explore the influencing factors of choroidopathy secondary to high myopia.A Nomogram risk prediction model for choroidopathy secondary to high myopia was constructed based on the influencing factors and externally validated.Results In groups A and B,the age,proportion of diabetes mellitus,axial length,and level of seruim transforming growth factor β1(TGF-β1)of patients in subgroup a were higher than those in the subgroup b,and the diopter was lower than that in the subgroup b(all P＜0.05).The Logistic regression analysis showed that age,diabetes mellitus,axial length and serum TGF-β1 level were independent risk factors for choroidopathy secondary to high myopia,and diopter was a protective factor(all P＜0.05).Age,diabetes mellitus,axial length and serum TGF-β1 level were positively correlated risk factors for choroidopathy secondary to high myopia,and diopter was a negatively correlated risk factor(all P＜0.05).The area under the curve of the Nomogram risk prediction model for predicting choroidopathy secondary to high myopia was 0.818,and the calibration was good.Con-clusion Age,diabetes mellitus,axial length,diopter and serum TGF-β1 level are the influential factors for choroidopa-thy secondary to high myopia.The Nomogram risk prediction model established based on these factors has a certain value for predicting choroidopathy secondary to high myopia.The clinical therapeutic schedules should be made based on this model to reduce the risk of secondary choroidopathy.

Influencing factors and prediction model construction of diffuse chorioretinal atrophy in patients with high myopia / 眼科新进展

Objective To investigate the factors that lead to diffuse chorioretinal atrophy(DCA)in patients with high myopia(HM)and to establish a prediction model.Methods In this retrospective case-control study,a total of 169 HM patients(338 eyes)admitted to the Department of Ophthalmology,Harbin 242 Hospital from October 2018 to October 2022 were selected.All patients underwent comprehensive ophthalmic examination at the time of inclusion.The incidence of DCA was evaluated according to the International Photographic Classification and Grading System for myopic maculopa-thy,and the risk factors of DCA in HM patients were analyzed by multivariate Logistic regression.The predictive model of DCA in HM patients was established by the receiver operating characteristic curve(ROC)based on risk factors,and the calibration degree of the predictive model was tested by Hosmer-Lemeshow(H-L).Results Among the 169 patients,34 patients were divided into the DCA group,and 135 patients were divided into the non-DCA group;there were statistically significant differences in age and gender distribution between the two groups(both P＜0.05).The axial length(AL),pat-tern standard deviation(PSD),positive rate of carbonic anhydrase 2(CAII)antibody in the DCA group were higher than those in the non-DCA group,while the best corrected visual acuity(BCVA),mean defect(MD)of the visual field,spheri-cal equivalent(SE),deep retinal microvessel density(MVD)and serum 25-hydroxyvitamin D[25(OH)D]were lower than those in the non-DCA group(all P＜0.05).Older age,longer AL and positive CAII antibody were the risk factors for DCA in HM patients(all P＜0.05),while greater deep retinal MVD and higher 25(OH)D were the protective factors(both P＜0.05).ROC analysis showed that the area under the curve of the prediction model for DCA in HM patients was 0.864(95％CI:0.802-0.911,P＜0.001),and the sensitivity and specificity were 85.29％and 88.15％,respectively.According to the H-L test,the prediction model for DCA in HM patients was relatively consistent with the actual results(P＞0.05).Con-clusion The occurrence of DCA in HM patients is affected by age,AL,CAII antibody,deep retinal MVD and 25(OH)D level,and a prediction model established based on the above factors can predict the risk of DCA well.

Correlation between cerebral atrophy and total burden of cerebral small vessel disease in patients with recent small subcortical infarct / 中华老年心脑血管病杂志

Objective To investigate the relationship between cerebral atrophy and total burden of cerebral small vessel disease in patients with recent small subcortical infarct(RSSI).Methods A total of 194 elderly RSSI patients admitted to Department of Neurology of Changzhou Second People's Hospital Affiliated to Nanjing Medical University from September 2021 to November 2022 were recruited in this study.All patients completed cranial MRI examination and were divid-ed into a non-mild group 1(97 cases)and a moderate to severe group 1(97 cases)based on the to-tal burden of cerebral small vessel diseases(CSVD)imaging.Visual assessment scale was used to assess the severity of brain atrophy in the whole brain and various regions of the brain.According to the global cortical atrophy scale(GCA)score,all patients were divided into a non-mild group 2(88 cases)and a moderate to severe group 2(106 cases).Brain atrophy in various regions,medial temporal lobe atrophy(MTA)score,frontal temporal lobe atrophy(FTA)score,and posterior cortical atrophy(PA)score were evaluated.Their general clinical and imaging data were collected,multivariate logistic regression analysis was employed to analyze the relationship between GCA score and total burden of CSVD imaging in RSSI patients,and Spearman correlation analysis was further adopted to explore the correlation of GCA score and different parts of brain atrophy with total burden of CSVD imaging.Results When compared with the non-mild group 1,the moderate to severe group 1 had significantly larger proportions of having GCA score of 2-3 points,PA score of 2-3 points,MTA score of 2-4 points and FTA score of 2-4 points(P＜0.01).The ra-tio of having 2-4 points in total imaging burden score of CSVD was obviously higher in the mod-erate to severe group 2 than the non-mild group 2(P＜0.01).Multivariate logistic regression anal-ysis showed that age and total burden of CSVD imaging were independent risk factors for brain atrophy in RSSI patients(OR=1.184,95％CI:1.099-1.276,P=0.000;OR=3.537,95％CI:1.664-7.518,P=0.001).Spearman correlation analysis revealed that the total burden score of CSVD imaging was positively correlated with GCA,MTA,FTA and PA scores in RSSI patients(r=0.518,r=0.382,r=0.471,r=0.388,P=0.000).Conclusion The total burden of CSVD is an independent risk factor for GCA in elderly RSSI patients.The more serious the total burden of CSVD is,the higher the grade of GCA is.The total burden of CSVD is related to the whole brain and brain atrophy in other different regions of the brain.

Interpretation of the 2022 diagnostic criteria for multiple system atrophy / 中华老年医学杂志

Multiple system atrophy(MSA)is a serious and rapidly progressive neurodegenerative disease.The currently used diagnostic criteria are the second edition of MSA diagnostic criteria published in 2008.Although widely recognized in clinical research, they lack sensitivity for early diagnosis of the disease.Reliable early diagnosis of MSA is particularly important for patient care and counseling, recruitment for clinical trials of disease-modifying therapies, and development and validation of diagnostic tools.To overcome the shortcomings of the second edition of the diagnostic criteria, the International Parkinson and Movement Disorder Society developed a new version of diagnostic criteria for MSA, which was published in April 2022.This paper interprets the new MSA diagnostic criteria and examines the scientific research areas that need to be further explored in future research, which will be important in guiding the management of elderly patients and related research.

Clinical heterogeneity and cluster analysis of multiple system atrophy / 中华老年医学杂志

Objective:To examine the clinical subtypes of patients with multisystem atrophy(MSA)that may indicate the prognosis of patients.Additionally, we aim to compare the ability to perform daily activities among patients of each subtype using cluster analysis.Methods:The retrospective analysis included demographic data, clinical symptoms and signs, scale scores, and ancillary examinations of 94 patients diagnosed with multisystem atrophy at Xuanwu Hospital of Capital Medical University.The study aimed to analyze the clinical characteristics of each subtype obtained through clustering.Additionally, a comparison was made between patients with traditional motor subtypes and those with new subtypes in terms of activities of daily living.The study consisted of 94 MSA patients, with an average age of 61 years and a female representation of 51.1%.Using the data collected on the continuum, a full linkage hierarchical cluster analysis was performed to classify MSA patients into four clinical subtypes: gait disorder(17 cases, 18.1%), malignant tonic hyperkinetic with premature haircut(25 cases, 26.6%), intermediate(43 cases, 45.7%), and autonomic benign type(9 cases, 9.6%).Each subtype exhibited various clinical motor and non-motor symptoms, including UPDRS-Ⅲ( χ2=27.90, P<0.001), gait disturbance( χ2=33.23, P<0.001), MoCA( χ2=10.98, P=0.012), HAMA( χ2=12.14, P=0.007), HAMD( χ2=13.62, P=0.003), smell score( χ2=10.16, P=0.017), postural hypotension( χ2=14.59, P=0.028), and a statistically significant difference in the ability to perform daily living score( χ2=25.35, P<0.001).No statistically significant differences in non-motor symptoms and activities of daily living abilities were observed between the cerebellar and Parkinsonian types of traditional motor typing( P>0.05). Conclusions:The hierarchical clustering analysis conducted in this study reveals that the clinical phenotype of MSA provides a more accurate reflection of patients' clinical characteristics and their impact on quality of life compared to the traditional motor phenotype.Additionally, it may help predict variations in the underlying pathological impairment and the rate of disease progression.These findings offer a foundation for precise diagnostic interventions in patients with MSA.

Study on the similarities and differences of orthostatic hypotension in patients with Parkinson′s disease and multiple system atrophy / 中华神经科杂志

Objective:To summarize and compare the characteristics of orthostatic hypotension (OH)　in　patients　with　Parkinson′s disease and multiple system atrophy (MSA).Methods:The active standing test data of 210 Parkinson′s disease patients (Parkinson′s disease group) and 85 MSA patients (MSA group) admitted to the Department of Neurology, Xuanwu Hospital, Capital Medical University from January 2021 to March 2022 were retrospectively analyzed. Demographic information, clinical data, Hoehn-Yahr staging, and Unified Parkinson′s Disease Rating Scale (UPDRS), Non-Motor Symptoms Questionnaire (NMSQ), Montreal Cognitive Assessment Scale and Mini-Mental State Examination scores were collected. The comparative analysis of OH was conducted according to the changes of heart rate and blood pressure during the active standing test.Results:Among the 85 patients with MSA, 52 were found with MSA parkinsonism variant (MSA-P) and 33 with MSA cerebellar variant (MSA-C). The 210 Parkinson′s disease patients were aged (61.5±11.0) years, with 116 males (55.2%). The 85　MSA　patients　were aged (60.1±6.8) years, with 44 males (51.8%). Compared with the Parkinson′s disease group, the Hoehn-Yahr staging [2.0(2.0, 3.0) vs 3.0(2.0, 3.0), Z=-5.278, P<0.001], NMSQ[ 25.0(11.0,46.5) vs 45.0(24.0,70.0), Z=-3.632, P<0.001] and UPDRS scores [50.0(32.0,68.0) vs 65.5(44.5,78.5), Z=-3.073, P=0.003] in the MSA group were higher. The incidence of OH in the MSA group was higher than that in the Parkinson′s disease group [63.5% (54/85) vs 25.7%(54/210), χ 2= 37.284, P<0.001], but there was no statistically significant difference between the MSA-P and MSA-C groups . Compared with the Parkinson′s disease group, the MSA group had a higher incidence of classical OH [54.1%(46/85) vs 12.9%(27/210), χ 2=55.316, P<0.001] and neurogenic OH [36.5%(31/85) vs 9.0%(19/210), χ 2=32.326, P<0.001],but there was no statistically significant difference in the incidence of initial OH and delayed OH between the two groups. The incidence of severe OH in the MSA group was also higher than that in the Parkinson′s disease group [57.6%(49/85) vs 16.7%(35/210), χ 2=49.894, P<0.001], but there was no statistically significant difference in the incidence of pre-clinical OH and mild OH between the two groups. Conclusions:The incidence, time change, severity and pathophysiological basis of OH in Parkinson′s disease and MSA patients are different. Different types of OH may help to distinguish MSA from Parkinson′s disease.

The c.91C>T mutation in DNAJB2 gene associated distal hereditary motor neuropathy and early-onset Parkinson′s disease: a family report / 中华神经科杂志

A family carrying a homozygous variant of DNAJB2 gene C.91C>T (p.His31Tyr) with distal hereditary motor neuropathy (dHMN) associated with early-onset Parkinson′s disease was reported. The patient presented with distal limb weakness and atrophy at the early stage of the disease, and developed Parkinson′s symptoms more than 10 years later. Neuroelectrophysiological examination suggested motor and sensory axonal involvement. This mutation site had not been reported and was considered to be a neogenic mutagenicity of dHMN, excluding other mutations that can cause early-onset Parkinson′s disease.

The genetic and clinical features of MORC2 gene-related neuropathy in Chinese patients / 中华神经科杂志

Objective:To summarize the genetic and phenotypic features of MORC family CW-type zinc finger 2 (MORC2) gene-related neuropathy in Chinese patients. Methods:The clinical and whole exome sequencing data of MORC2 gene-related neuropathy families with a definitive genetic diagnosis were collected from the Third Xiangya Hospital of Central South University between 2010 and 2023. Literature involving Chinese families with MORC2 gene-related neuropathy was extensively reviewed to provide a comprehensive summary of the genetic and phenotypic spectrum of the disease. Results:A total of 10 families with MORC2 gene-related neuropathy were identified and analyzed. Six different heterozygous pathogenic variants in the MORC2 gene were observed among these families, including the novel variant c.1330G>C (p.G444R) that had not been previously reported. Six families presented as axonal Charcot-Marie-Tooth disease caused by variants in the MORC2 gene (CMT2Z) phenotype with childhood or adult onset, and carried variants c.754C>T (p.R252W), c.1199A>G (p.Q400R), c.1330G>C (p.G444R), or c.1396G>A (p. D466N); 3 families manifested as severe spinal muscular atrophy (SMA)-like phenotype with infantile onset, all carried c.260C>T (p.S87L); 1 family carried c.1181A>G (p.Y394C), presented as DIGFAN syndrome phenotype with infantile onset combined with mental and motor retardation. Systematic review showed 8 Chinese families carried pathogenic variants of the MORC2 gene, among which 5 families were associated with the CMT2Z phenotype, carrying c.754C>T (p.R252W), c.1079A>G (p.E360G), c.1220G>A (p.C407Y), or c.1397A>G (p.D466G); 1 family was associated with SMA-like phenotype, carrying c.260C>T (p.S87L); and 2 families were associated with DIGFAN syndrome, carrying c.79G>A (p.E27K) and c.292G>A (p.G98R). Conclusions:A novel pathogenic variant c.1330G>C (p.G444R) of the MORC2 gene associated with the CMT2 phenotype is reported. Eleven pathogenic variants of the MORC2 gene have been reported in the Chinese patients to date, and c.754C>T(p.R252W) may be the most common. Patients with MORC2 gene-related neuropathy carrying different variants present with significant clinical heterogeneity, manifesting as CMT2Z, early-onset severe SMA-like myasthenia, or DIGFAN syndrome.

Optimization of biopsy strategies for risk related staging of gastric cancer / 中华消化内镜杂志

Objective:To investigate the correlation of atrophy and intestinal metaplasia (IM) stage with gastric cancer and to optimize biopsy strategy.Methods:Data of patients who underwent endoscopy and five-point biopsy at Shandong Provincial Hospital between November 2020 and October 2022 were collected. The baseline characteristics of gastric cancer and non-gastric cancer patients, as well as the occurrence and severity of atrophy and IM in different areas were compared. Logistic regression analysis was used to evaluate the correlation of operative link for gastritis assessment (OLGA) and operative link for gastric intestinal metaplasia assessment (OLGIM) staging with gastric cancer. The Kendall tau correlation coefficient was used to compare the consistency of different biopsy strategies (two-point, three-point, and four-point) with the standard five-point biopsy in OLGA and OLGIM staging. Receiver operating characteristic (ROC) curve analysis was further performed to compare the diagnostic performance of different biopsy strategies in identifying the OLGA and OLGIM Ⅲ-Ⅳ stage.Results:A total of 122 patients were included in the analysis, with age of 61.0±10.0 years. Multivariate analysis showed that OLGA staging was not associated with gastric cancer ( P=0.788), while OLGIM Ⅲ-Ⅳ staging was significantly correlated with gastric cancer ( P=0.006, OR=3.39, 95% CI: 1.41-8.17). The occurrence of atrophy and IM were higher in lesser curvature of the antrum [56.6% (69/122) and 66.4% (81/122)] and incisura angularis [57.4% (70/122) and 52.5% (64/122)], with higher severity, while lower in greater curvature of the corpus [2.5% (3/122) and 5.7% (7/122)], with lower severity. The consistency of four-point and three-point biopsies with standard five-point biopsy in OLGA and OLGIM staging was high. The consistency of three-point biopsy in incisura angularis, lesser curvature of the antrum and corpus was exceptionally high among them, with correlation coefficients of 0.969 and 0.987, respectively. Conclusion:OLGIM Ⅲ-Ⅳ stages increase the risk of gastric cancer. Three-point biopsy in incisura angularis, lesser curvature of the antrum and corpus are recommended for the screening and monitoring of atrophy or IM.

Research advance in geographic atrophy due to age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

Geographic atrophy(GA)is an intermediate and advanced stage of age-related macular degeneration(ARMD). Due to the complex pathogenesis of GA, there are no effective treatments at present, and eventually patients will lose central vision. Studies have shown that excessive activation of the complement system is closely related to the occurrence and progression of GA. This review will offer a summary of the clinical features, pathogenesis, the role of complement system in the pathology and the treatment progress of GA.