Age and sex differences in the impact of common comorbidities on stroke and myocardial infarction: results from the China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project.

OBJECTIVES: This study aims to evaluate the age- and sex-specific associations of comorbidities with stroke and MI and further calculate the population-attributable fractions (PAFs) of five comorbid diseases for stroke and myocardial infarction (MI) by age and sex. STUDY DESIGN: This is a prospective cohort study. METHODS: This study leveraged data from a sub-cohort of the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project. Participants aged 35-75 years without a prevalent stroke and MI were enrolled from January 2016 to December 2020, with follow-up through December 2021. Five common comorbidities were collected at baseline, and the study outcome was hospitalization for stroke and MI identified from the Inpatients Registry. RESULTS: Of 100,873 participants, the mean age was 54.2 (±10.2) years, 34.2% were ≥60 years old, and 60.8% were women. After a median follow-up of 3.52 years, 4156 participants had stroke/MI. The strengths of the associations between hypertension, diabetes, and obesity with stroke/MI were higher in younger individuals than in seniors, and obesity had a more hazardous impact on stroke/MI in men than in women. The five comorbidities collectively explained a higher population attributable fraction (PAF) for stroke/MI in the young group (51.5[46.9, 55.7] %) than in the senior group (41.3[37.0, 45.4] %), in men (45.6[40.9, 49.9] %) than in women (41.1[36.1, 45.7] %). CONCLUSIONS: Most of the common comorbidities were significantly associated with stroke and MI. Several age and sex differences in the impacts of comorbidities on stroke/MI were observed, highlighting the importance of age- and sex-specific preventive strategies to reduce premature stroke and MI.

Effects of a diabetes education program integrated with text-message support for lifestyle change among older individuals with type 2 diabetes in communities: a randomised controlled trial.

OBJECTIVE: The objective of this study was to investigate the effects of self-management education integrated with text-message support (SME-TMS) on glycaemic control in individuals with type 2 diabetes. STUDY DESIGN: a randomized, controlled trial. METHODS: Patients from two communities were randomized into the intervention group (n = 53) or the control group (n = 52). The six-month intervention included the culturally tailored diabetes education and text-messaging support for behaviour changes. The control group received treatment as usual. The primary outcome was reductions in HbA1c and fasting blood glucose at six-month non-intervention follow-up. Secondary outcomes were reductions in body weight, body mass index (BMI), blood pressure, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, physical activity, and health beliefs. RESULTS: The intervention led to substantially increase days of weekly physical activity (42% vs. 0%, P < 0.001) and health beliefs (coefficient = 7.0, 95% confidence interval [CI]: 4.4 to 9.6, P < 0.001). However, no greater reduction was found in HbA1c at six months after the intervention, compared with the control group (0.13%, 95% CI: -0.20 to 0.46, P = 0.443). The reductions of blood pressure, TC, and LDL-C were greater in the control group than in the intervention group (all P < 0.050). Within the intervention group, participants had significant reduction in BMI, whereas the control group had greater reductions in TC and LDL-C (all P < 0.050). CONCLUSIONS: The SME-TMS intervention led to a greater increase in the weekly physical activity and health belief score in the older patients at 6-month follow-up than with the usual care. Further research is needed to ascertain how these benefits could be translated into favorable medium-and long-term glycaemic control. TRAIL REGISTRATION NUMBER: This study was registered on Chinese Clinical Trials Registry (ChiCTR2300075112).

[Analysis of MTHFR gene variants in fifteen children with hyperhomocysteinemia].

The clinical manifestations, biochemical and metabolic data, genetic variations and treatment data of children with MTHFR gene variant induced hyperhomocysteinemia admitted to Hangzhou Children's Hospital and Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from November 2015 to September 2021 were analysed retrospectively. A total of 15 pediatric patients were included, including 10 males and 5 females, with onset ages ranging from 6 days to 18 years old and confirmed ages ranging from 40 days to 18 years old. One confirmed case was detected through neonatal screening, and the remaining 14 cases were all diagnosed through genetic diagnosis after onset. The main clinical manifestations were feeding difficulties, hypotonia, epilepsy, developmental delay. All patients had elevated levels of blood homocysteine, with blood homocysteine levels before and after treatment being (151.46±57.44) µmol/L and (69.96±32.88) µmol/L, significantly decreased after treatment compared with before treatment, with a statistically significant difference (P<0.001). The blood methionine level before the treatment was 9.40 (6.20, 11.96) µmol/L, normal or slightly decreased compared to the reference range. The methionine level returned to normal after treatment. A total of 19 MTHFR gene variants were detected, with 6 being unreported variants and 13 being known variants. c.1316C>T (p.L439P) was the most common variant(16.6%,5/30). All the patients had varied neurological damages, with 7 patients improved after metabolic therapy by carnitine and folinic acid, 8 patients experiencing developmental delay, and 1 patient experiencing frequent epilepsy. The clinical manifestations of MTHFR gene variation-related hyperhomocysteinemia are complex and variable. Early-onset and homozygous variants often have a poor prognosis. Blood homocysteine, blood amino acid analysis, serum total homocysteine assay and gene testing are helpful for early diagnosis.

[Progress in clinical application of humoral biomarkers for central nervous system inflammatory demyelinating diseases].

Central nervous system idiopathic inflammatory demyelinating diseases (CNS-IIDD) is an autoimmune disorder characterized by inflammatory demyelination. The disease follows a course of recurrent attacks and remission, with some cases displaying continuous progression, often resulting in disability. The incidence of CNS-IIDD has been increasing, imposing a substantial burden on both patients' families and society in recent years. A promising strategy for disease management involves the identification of humoral biomarkers to diagnose CNS-IIDD and predict disease attack and progression. Such biomarkers could aid in identifying individuals at high risk of disability, enabling targeted preventive interventions. This study summarizes advancements in the identification of humoral biomarkers and their potential for predicting disease activity and progression to offer novel insights into the management of CNS-IIDD.

[Correlation analysis of urinary arsenic species and health effect indicators of occupational arsenic exposure workers].

Objective: To explore the correlation between urinary arsenic and health effects through the determination and analysis of urinary arsenic levels in occupational arsenic exposed workers. Methods: In November 2021, 95 workers exposed to arsenic and its inorganic compounds and 31 administrative personnel from a non-ferrous metal smelter in Yunnan Province were selected as the contact group and control group, respectively. Urine forms of arsenic, blood tumor markers, liver function were detected, and micronucleus test was used to analyze the chromosome damage. The correlation between urine forms of arsenic and health effects were analyzed. Results: Compared with the control group, the concentrations of urinary trivalent inorganic arsenic (iAs(3+)) , pentavalent inorganic arsenic (iAs(5+)) , inorganic arsenic (iAs=ΣiAs(3+)+iAs(5+)) , monomethyl arsenic (MMA) , dimethyl arsenic (DMA) and urinary arsenic (ΣiAs+MMA+DMA) at the end of class in contact group were higher (P<0.05) . There was no statistically significant difference in blood tumor markers and liver function indicators between the two groups (P>0.05) . Compared with the control group, the peripheral blood micronucleus rate and cell micronucleus rate in the contact group were significantly increased (P<0.05) . The urinary arsenic, iAs(5+), inorganic arsenic and DMA were positively correlated with peripheral blood micronucleus rate in contact group (r(s)=0.48, 0.34, 0.37, 0.23, P<0.05) , and the urinary arsenic, iAs(5+), DMA were positively correlated with peripheral blood micronucleus rate (r(s)=0.48, 0.34, 0.26, P<0.05) . Conclusion: There is a significant correlation between different valence states of arsenic in the urine and abnormal health effects of occupational arsenic exposed workers. It is necessary to strengthen the detection of arsenic species in the urine of occupational arsenic exposed workers to better protect their health.

Performance of a generative adversarial network using ultrasound images to stage liver fibrosis and predict cirrhosis based on a deep-learning radiomics nomogram.

AIM: To investigate the performance of a generative adversarial network (GAN) model for staging liver fibrosis and its radiomics-based nomogram for predicting cirrhosis. MATERIALS AND METHODS: This two-centre retrospective study included 434 patients for whom input data of ultrasound images and histopathological data (obtained within 1 month of ultrasound examinations) were assigned to the training cohort (249 patients), the internal cohort (92 patients), and the external (93 patients) cohort. A data augmentation method based on a GAN model was used. The discriminative performance was evaluated for classifying fibrosis of S4 and ≥S3. Deep-learning radiomics features were extracted for the prediction of cirrhosis (S4). To perform feature reduction and selection, the least absolute shrinkage and selection operator (LASSO) algorithm was applied. Radiomics scores, along with clinical factors, were incorporated into a nomogram using multivariable logistic regression analysis. The performance of the models was estimated with respect to discrimination power, calibration, and clinical benefits. RESULTS: The areas under the receiver operating characteristic curve (AUCs) values of the GAN were 0.832/0.762 (≥S3), and 0.867/0.835 (S4) for internal/external test sets, respectively. The radiomics nomogram that intergrated radiomics scores and clinical factors showed good calibration and discrimination ability of 0.922 (AUC) in the training dataset, 0.896 in the internal dataset, and 0.861 in the external dataset. Decision curve analysis (DCA) demonstrated that the nomogram outperformed radiologist and haematological indices in terms of the most clinical benefits. CONCLUSIONS: The GAN model could be applied to discriminate fibrosis stages, and a favourable predictive accuracy for diagnosing cirrhosis was achieved using a deep-learning radiomics nomogram.

[Predictive value of plasma TMAO combined with NT-proBNP on the prognosis and length of hospitalization of patients with ischemic heart failure].

Objective: To explore the value of the assessment of plasma trimethylamine N-oxide (TMAO) combined with N-terminal pro-B-type natriuretic peptide (NT-proBNP) on predicting the all-cause mortality, length of hospitalization, and hospital cost in ischemic heart failure (IHF) patients. Methods: This prospective cohort study included 189 patients (157 males, mean age (64.0±10.5) years) with a left ventricular ejection fraction<45% caused by coronary artery disease, who hospitalized in our department from March 2016 to December 2020. Baseline data, including demographics, comorbid conditions and laboratory examination, were analyzed. The cumulative rate of all-cause mortality was evaluated using the Kaplan-Meier method and compared between the groups according to the log-rank test. Relative risks were reported as hazard ratios (HR) and 95% confidence interval (95%CI) calculated using the Cox proportional-hazards analysis, with stepwise adjustment for covariables. Spearman correlation analysis was then performed to determine the relationship between TMAO combined with NT-proBNP and length of hospitalization and hospital cost. Results: There were 50 patients in the low TMAO+low NT-proBNP group, 89 patients in high TMAO or high NT-proBNP group, 50 patients in high TMAO+high NT-proBNP group. The mean follow-up period was 3.0 years. Death occurred in 70 patients (37.0%), 27 patients (54.0%) in high TMAO+high NT-proBNP group, 29 patients (32.6%) in high TMAO or high NT-proBNP group and 14 patients (28.0%) in low TMAO+low NT-proBNP group. TMAO, in combination with NT-proBNP, improved all-cause mortality prediction in IHF patients when stratified as none, one or both biomarker(s) elevation, with the highest risk of all-cause mortality in high TMAO+high NT-proBNP group (HR=3.62, 95%CI 1.89-6.96, P<0.001). ROC curve analysis further confirmed that TMAO combined with NT-proBNP strengthened the prediction performance on the risk of all-cause death (AUC=0.727(95%CI 0.640-0.813), sensitivity 55.0%, characteristic 83.1%). Spearman correlation analysis showed that IHF patients with high TMAO and high NT-proBNP were positively associated with longer duration of hospitalization (r=0.191,P=0.009), but not associated with higher hospital cost (r=0.030, P=0.686). Conclusions: TMAO combined with NT-proBNP are valuable prediction tool on risk stratification of patients with IHF, and those with two biomarkers elevation face the highest risk of mortality during follow-up period, and are associated with the longer hospital stay.

[Effects of p16/pRb and JNK signaling pathways in hydroquinone-induced malignant transformation of TK6 cells].

Objective: To investigate the cell cycle and apoptosis in hydroquinone (HQ) -induced malignant transformation of TK6 cells and its related regulatory mechanisms. Methods: TK6 cells were exposed to 20 µmol/L HQ, 24 h/time, once a week, for 19 weeks as experimental group and TK6 cells treated with phosphate buffer (PBS) for 19 weeks was used as control group from March 2014. In regulatory mechanism research, the cells were divided into four groups: control group, experimental group, control inhibitor group and experimental inhibitor group (inhibitor groups were added 10 µmol/L P600125) . Cell cycle and apoptosis were detected by flow cytometry. The protein expression of cell cycle-related proteins and JNK signaling pathway proteins were detected by Western blot. Results: Flow cytometry showed that compared with control group, the ratio of cells in the G0/G1 phase of the experimental group was significantly decreased (P=0.001) , and the ratio of cells in the S phase was significantly increased (P=0.002) . Western blotting demonstrated that the protein expressions of p-Rb (Ser780) , E2F1, Cyclin D1, p-p16 (Ser152) , JNK1, p-JNK1 (Thr183/Tyr185) , c-jun, p-c-jun (Ser63) (P=0.015, 0.021, 0.001, 0.001, 0.005, 0.001, 0.039, 0.003) were up-regulated, while the protein expressions of Rb (P=0.048) and p16 (P=0.002) were significantly down-regulated. After exposed to SP600125, compared with experimental group, there were no significant changes in cell cycle distribution (P=0.946) and apoptosis rate (P=0.923) in experimental inhibitor group. The expression of c-jun (P=0.040) protein was down-regulated, while the expression of Rb (P=0.027) protein was up-regulated in experimental inhibitor group. Conclusion: In HQ-induced TK6 cells malignant transformation, the cell cycle is arrested in the S phase, and the p16/pRb signaling pathway is inhibited, while the JNK signaling pathway is activated. However, the activated JNK signaling pathway may not be involved in the regulation of cell cycle.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is associated with IRF7, BANK1 and TBX21 polymorphisms in two populations.

BACKGROUND AND PURPOSE: Autoantibodies targeting the GluN1(NR1) subunit of the anti-N-methyl-D-aspartate receptor (NMDAR) cause encephalitis. Although it has been shown that anti-NMDAR encephalitis is associated with human leukocyte antigen (HLA) loci, susceptibility genes for the disease outside the HLA loci remain unidentified. In this study, we aimed to explore the association of anti-NMDAR encephalitis with non-HLA genes. METHODS: Two Chinese anti-NMDAR encephalitis cohorts from Han populations were recruited for this study. The North Chinese case-control set consisted of 98 patients and 460 controls, while the South Chinese case-control set included 78 patients and 541 controls. All participants were genotyped for 28 single nucleotide polymorphisms that are associated with autoimmune disorders or infectious diseases. RESULTS: In two independent case-control sets, we identified significant associations of anti-NMDAR encephalitis with IRF7 rs1131665 (odds ratio [OR] 3.34, 95% confidence interval [CI] 1.99-5.63; P < 0.000001, Padjusted  = 0.00004), BANK1 rs4522865 (OR 1.44, 95% CI 1.15-1.82; P = 0.0017, Padjusted  = 0.0149), and TBX21 rs17244587 (OR 2.03, 95% CI 1.35-3.05; P = 0.00051, Padjusted  = 0.0066). Furthermore, analysis of the three polymorphisms with clinical features of the disease revealed that the IRF7 rs1131665 was associated with tumor status. CONCLUSION: The present study has for the first time identified non-HLA susceptibility genes for anti-NMDAR encephalitis. The association of IRF7, BANK1 and TBX21 with anti-NMDAR encephalitis suggests that B-cell activation, Th1 responses, virus infection and the type I interferon signaling pathway are involved in the pathogenesis of the disease.

[Establishment and consistency verification of the standard operation procedure for laboratory detection of immunoglobulin G oligoclonal bands in cerebrospinal fluid].

Objective: To establish the standard operation procedure (SOP) for detection of oligoclonal band (OCB) in cerebrospinal fluid (CSF) and verify consistency by using this SOP in different laboratories. Methods: The SOP for detection of CSF-OCB fluid was successfully established by an expert feedback approach. Neuroimmunology laboratories in 3 representative Chinese three-tier research hospitals were selected for this study, and commercially available protein electrophoresis automation systems and detection SOP were set up. The quality control product was provided by the College of American Pathologists (CAP) and Sebiacompany were used for interior quality and compared to each other, respectively. Seventeen serum and CSF paired samples were tested and compared using the same SOP. Kappa test or Kendall W test were adopted to evaluate the inter-laboratory consistency among different hospitals. Results: The results of repeated testings in a single hospital suggested that the 2-and 4-fold dilution for CSF-OCB were reported as positive, while 64-and 128-fold dilution were reported as negative. Positive or negative inconsistencies were reported in 8-, 16-, and 32-fold dilution. After increasing the number of repetitions, the results showed that both 16-and 32-fold dilution were reported as negative, and 8-fold dilution exhibited negative results (2 positive results for 40 repetitions, coincidence rate=95%).The results of multi-center inter-laboratory quality assessment showed that the detection consistency rate among 3 hospitals was 100% (Kappa value =1). Conclusions: The SOP to detect CSF-OCB established in this study demonstrates a good repeatability and stability. Therefore,such SOP would be a good reference for diagnostic laboratories to detect CSF-OCB in China.

[Clinical features and gene mutations of 6 patients with carnitine palmitoyltransferase 1A deficiency].

The clinical and biochemical data and gene sequencing results of patients with carnitine palmitoyltransferase 1A deficiency were analyzed, in order to improve the understanding of the disease. Six patients (5 males and 1 female, aged from 1 to 8 years old) with carnitine palmitoyltransferase 1A deficiency from Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital between 2008 and 2019 were included. Two cases were detected by neonatal screening and had no clinical symptoms. The remaining 4 cases all showed seizures induced by fever, vomiting or diarrhea. All the 6 patients showed increased serum free carnitine (C0), decreased hexadecanoylcarnitine (C16) and octadecanoylcarnitine (C18), and increased C0/(C16+C18). Meanwhile, compound heterozygous mutations of CPT1A gene were detected in all 6 patients, of which 2 were reported mutations (c.281+1G>A and c.968-8C>T), and 10 were new mutations. The new mutations included 6 missense mutations, 1 nonsense mutation, 1 deletion mutation and 2 splicing mutations. Detection of free carnitine and acyl carnitine by tandem mass spectrometry is helpful for early screening and diagnosis of carnitine palmitoyltransferase 1A deficiency.

[Policy analysis of disease control and prevention system in China from the perspective of policy instruments from 2000 to 2020].

Objective: To analyze the related polities about disease control and prevention system in China from 2000 to 2020, and to provide implication for the policy formulation of disease control and prevention system in the future. Methods: Policy documents were searched in the official websites of relevant government departments including the State Council, National Health Commission, National Development and Reform Commission, Ministry of Human Resources and Social Security, and Ministry of Finance by using the keywords related to disease control and prevention from 2000 to 2020. Thematic framework and content analysis were performed to analyze the eligible policy documents based on the theory of policy instruments. Results: A total of 37 policy documents were included in this study. The application of single policy instrument was common (81.1%), of which the capacity building instrument was the most frequently used (32.4%), followed by mandate instrument (21.6%) and inducement instrument (13.5%), while system-changing instrument (8.1%) and symbolic and hortatory instrument were less used (5.4%). The main policy themes were personnel system (15.2%) and system construction (15.2%), followed by personnel development (13.0%) and information construction (2.2%). Conclusion: In the policy formulation process, the government should strengthen the comprehensive application of multiple policy instruments. Particularly about the inducement instrument and symbolic and hortatory instrument to further stimulate the internal motivation of disease control and prevention system and institutions in China.

[Structure quality of disease control and prevention system in China from 2002 to 2018].

Objective: To analyze the achievement of policy goals and actual changes of representative structure quality indicators related to disease control and prevention system during 2002-2018 in China. Methods: Quantified policy goals of structure quality including the number of workers, the proportion with bachelor degree and working environment were extracted from relevant policy documents and the data about representative structure quality indicators, including finance, human resources and working environment, were extracted from health statistics yearbooks. Comparative analysis was adopted in this study. Results: First, the designed policy goals were partly achieved. The number of workers per ten thousand people was lower than 1.75 in 2015. The target proportion of workers with bachelor degree was achieved by four year later in 2016. Only average building area per person was achieved according to the goal set in 2009. Second, it showed huge discrepancy among the proportion of financial subsidy, average personnel expenditure per person, and the number of workers at different levels of centers for disease control and prevention (CDC) from 2002 to 2018. The development of county-level CDCs was more restrained. Conclusion: Appropriate policy goals regarding financial support, human resources, and working environment should be strengthened at national level and quality improvement strategies should be established in the CDC system, particularly for county-level CDCs.

[Changes of the number of disease control and prevention staffs at provincial level in China from 2002 to 2018: an interrupted time series analysis].

Objective: To analyze the change of the number of staff at the provincial center for disease control and prevention (CDC) in China before and after the new health care reform. Methods: The data was from publicly reported health statistics yearbooks from 2002 to 2018. Descriptive analysis and interrupted time series analysis (ITS) were conducted in Stata/SE 15. Results: The decreasing trend of total number and average number of CDC staff per ten thousand people further exacerbated in the eastern and central areas after the new health care reform, while the total number of CDC staff in the western area changed from a decreasing trend to an increasing tend and the decreasing trend of average number of CDC staff per ten thousand people slowed down. After controlling the provincial and time fixed effects, the ITS analysis showed that before the reform, the number of CDC staff in central area showed a decreasing trend (P=0.012). After the reform, no statistically significant changes were observed in the number of CDC staff in the eastern, central and western areas increased instantaneously (P>0.05), and the decreasing trend (slope) of the number of CDC staff in the eastern and central areas further increased. The number of CDC staff in the western area changed to an increasing trend (P>0.05). Conclusion: After the new health care reform, the total number and average number of CDC staff at the provincial level have not improved, therefore targeted reform strategies are needed to reverse the continuous reduction of CDC staff and reflect regional differences in the future.

[Research progress on building of disease control and prevention system of the international experience].

Through literature search in regular database and official websites of relevant countries, this paper combs and summarizes the main characteristics of disease prevention and control systems in five countries, the United States, Germany, South Korea, Australia and Japan, and the European Union at key levels including legal construction, organizational structure, financing, personnel construction and international cooperation, in order to provide decision support for the construction of disease prevention and control system in China in the future.

[The association between shift work and lower extremity osteoarthritis among retired workers].

Objective: To investigate the association between shift work and the risk of lower extremity osteoarthritis. Methods: The study population came from the Dongfeng-Tongji cohort established in 2008. In September 2008, the Dongfeng Motor Company in Hubei Province was to recruit all retired workers who voluntarily participated in the survey as the research objects. During the follow-up conducted from April to October 2013, a total of 14 438 retired workers, i.e. all of the participants who underwent physical examination were investigated about demographic characteristics, lifestyles, occupation history, and lower extremity joint-related medical history, and additionally completed lower extremity joint examinations. After excluding individuals with missing data regarding lower extremity osteoarthritis, with the history of lower extremity joint trauma, or with history of rheumatoid arthritis (N=532), data from 13 906 participants was analyzed in the study. Multivariate logistic regression models were used to estimate the association between shift work and lower extremity osteoarthritis. After stratified by the duration of shift work, multivariate logistic regression models were used to analyze the relationship between the duration after leaving from shift work and lower extremity osteoarthritis. Results: Finally, a total of 13 906 retired employees included 7 560 (54.4%) females with a mean age of 64.74 (standard deviation 8.23) years old. 5 537 (39.8%) workers had ever engaged in shift work, including 2 004 (14.4%) workers with 1-9 years of shift work and 3 533 (25.4%) workers with ≥ 10 years of shift work. The prevalence of lower extremity osteoarthritis was 7.0%, while the prevalence of knee osteoarthritis and hip osteoarthritis were 6.7% and 0.7%, respectively. Compared with daytime workers, shift workers showed a 22% increase in the risk of lower extremity osteoarthritis (OR=1.22, 95%CI:1.06-1.40). Each 5-year increase in the duration of shift work was associated with a 4% increase in the risk of lower extremity osteoarthritis (OR=1.04, 95%CI:1.01-1.08). With the extension of the duration after leaving from shift work, the risk of lower extremity osteoarthritis decreased. Similar relationships were found between shift work and the risk of knee osteoarthritis, as well as hip osteoarthritis. Conclusion: Shift work was associated with the increased risk of lower extremity osteoarthritis.

[Effects of different treatment and prevention regimens on myelin oligodendrocyte glycoprotein antibody-related optic neuritis].

Objective: To compare the effects of different treatment and prevention regimens on recovery and relapse rate in patients with myelin oligodendrocyte glycoprotein antibody-related optic neuritis (MOG-ON). Methods: Retrospective study of the records of 37 patients with MOG-ON in ZhongShan Ophthalmology Center from January 2014 to December 2018. Patients with first-ever MOG-ON (first-ever group) were subdivided into intravenous methylprednisolone pulse group (Pulse group) and high dose methylprednisolone without pulse regimen group (non-pulse group). Comparisons were taken on visual acuity (VA), visual field (VF), visual evoked potential amplitude (VEP) and retinal nerve fiber layer thickness (RNFLT). Effect of different prevention regimens, either low dose prednisone or low dose of prednisone (2.5-10 mg/Day) combined with mycophenolate mofetil (MMF) (0.5-1 g/Day) , as well as the annual relapse rate (ARR) were compared. Results: Among 25 patients of first-ever MOG-ON group (19 patients in pulse group and 6 patients in non-pulse group), VF of pulse group showed significant recovery, with MD value of (-7±8) dB at 1 m after onset and (-26±11) dB at onset (P<0.01), while non-pulse group showed significant VF recovery only at 6 m after onset, with MD value of (-9±9) dB at 6 m and (-22±11) dB at onset (P<0.01). However, no significant difference of VA, VF, VEP and RNFL could be found between the two groups on at all follow-up time points (P>0.05). Among 12 patients with at least one relapse (relapse group), 9 patients (75%) were given low-dose of prednisone plus MMF for relapse prevention. The ARR was 0.77 (0.21-4.5) before and 0 (0-0.41) after the regimen, respectively (P<0.05). Conclusion: Intravenous methylprednisolone pulse therapy in acute phase of MOG-ON may accelerate the recovery of visual function and improve the prognosis. Low-dose of prednisone combined with MMF may reduce the recurrence rate of MOG-ON.

[Clinical characteristics, treatment and prognosis of myelin oligodendrocyte glycoprotein antibody-associated optic neuritis in children].

Objective: To investigate the clinical characteristics, treatment and prognosis of myelin oligodendrocyte glycoprotein antibody-associated optic neuritis (MOG-ON) in pediatric patients. Methods: Clinical data, laboratory examination, the initial best corrected visual acuity (BCVA), fundus, neuroelectrophysiological results, MRI imaging, treatment and prognosis of children diagnosed with MOG-ON from 2016 to 2019 were retrospectively analyzed. Results: A total of 29 eyes from 16 children were involved, with a male/female ratio of 1∶1, onset age of (7.0±2.9) years. Seven of 16 patients had prodromal infection, with a unilateral/bilateral ratio of 3∶13, and 2 cases had recurrent optic neuritis. Before treatment, BCVA of 19 eyes (65.5%) was ≤0.1, among them, 4 had no sense of light, 5 had light sense, 5 with sense of hands in front of eyes, and 5 with sense of fingers in front of eyes. There were 10 eyes (34.5%) with BCVA of 0.1-0.5. After treatment, there were 4 eyes (13.8%), 5 eyes (17.2%) and 20 eyes (69.0%) in groups with BCVA of 0.1-0.5, 0.5-1.0, and>1.0, respectively. Twelve of 16 patients had optic papillitis in fundus examination during acute phase. The latency was prolonged and the amplitude was decreased in P100 wave of all the children. Thirteen out of 16 children showed swelling and thickening of optic nerve in MRI T2WI. MRI images exhibited intracranial demyelinating lesions in 12 of 16 children and long segment spinal cord lesions in 3 of 16 children. Thirteen of 16 patients showed effective results after intravenous methylprednisolone (IVMP) and intravenous immunoglobulin (IVIG) treatment. There was no relapse after administration of mycophenolate mofetil in 2 recurrent children. No progression after administration of rituximab was found in 1 child with corticosteroid insensitivity. The average follow-up time was (16±9) months and no recurrence occurred. Ten of 16 patients had full recovery, 4 had significant improvement, and 2 showed no significant improvement. Conclusions: There is no significant gender difference in the incidence of pediatric MOG-ON. Bilateral involvement and severe visual impairment are common in acute phase. Most patients have good response to IVMP combined with IVIG treatment and hence have a good prognosis. Only a few of them have neurological sequelae.

[Analysis of magnetic resonance imaging characteristics in Chinese patients with myelin oligodendrocyte glycoprotein antibody associated disorders].

Objective: To investigate the magnetic resonance imaging (MRI) characteristics in the brain and spinal cord of Chinese patients with myelin oligodendrocyte glycoprotein antibodies associated diseases (MOGAD). Methods: Forty nine MOGAD patients with seropositive MOG-IgG and 58 AQP4-IgG positive patients were enrolled in this study. The characteristics of brain and spinal cord MRI were retrospectively analyzed. Results: There was no significant difference in the proportion of abnormal brain MRI of the two groups (69.4% vs 65.5%, P=0.177) , while the proportion of abnormal spinal cord MRI of the AQP4-IgG positive group was significantly higher than that in the MOG-IgG positive group (84.5% vs 36.7%, P=0.001) . The proportion of MOG-IgG positive patients with subcortical white matter lesions and large lesions in the brain MRI was significantly higher than that in AQP4-IgG positive group (48.9% vs 13.8%, P=0.003, 46.9% vs 12.1%, P=0.000) . The longitudinally extensive transverse myelitis in spinal cord MRI of AQP4-IgG positive group was significantly higher than that in the MOG-IgG group (70.7% vs 24.5%, P=0.002) . In addition, the proportion of MOG-IgG positive child patients with large lesions in the brain was significantly higher than that in AQP4-IgG positive child patients (76.9% vs 20.0%, P=0.047) . Conclusion: Demyelinating MRI lesions caused by MOG-IgG are heterogeneous, and could lead to a wide range of clinical phenotypes which is significantly different from those with AQP4-IgG.

[Clinical features and prognosis of pediatric myelin oligodendrocyte glycoprotein antibody associated acute disseminated encephalomyelitis].

Objective: To analyze the clinical features, outcome and prognosis of pediatric myelin oligodendrocyte glycoprotein (MOG) antibody associated acute disseminated encephalomyelitis (ADEM), and provide evidence for improving the diagnosis and treatment of this disease. Methods: This study involved 30 MOG antibody-associated ADEM patients in the Department of Neurology, Guangzhou Women and Children's Medical Center. Patients' clinical information were analyzed. Results: The mean onset age was (5.2±3.3) years old, the ration of male to female was 16∶14. Fifty percent of these patients had a history of precede infection or vaccination before onset. Encephalopathy and seizures were the most common clinical manifestations, followed by movement disorder. In addition, some patients had other positive autoantibodies. Brain Magnetic resonance imaging (MRI) showed extensive, asymmetrical, indefinite large patchy lesions in bilateral cortical and subcortical areas and the spinal cord was characterized by long segmental myelitis. In acute attack, the patients had a good response to corticosteroid combined immunoglobulin therapy. Most of these patients had a good prognosis and recurrence rate was about 20%. Conclusions: The onset age of MOG antibody-associated ADEM is around 5 years old. Encephalopathy and seizures were the most common clinical manifestations. Most patients have a good response to corticosteroid combined immunoglobulin therapy. Some patients may have a recurrent disease course.