Objective:To investigate the clinical, phenotypic and genotypic features of hereditary hyperhomocysteinemia mainly involving the nervous system.Methods:The clinical data, physical examination, imaging results, blood-urine tandem mass spectrometry analysis and genetic results of 8 patients with hyperhomocysteinemia from the Department of Neurology of the Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from September 2020 to December 2023 were collected, and the clinical, genetic features and pathogenic mechanisms of these patients were summarized and analyzed.Results:Among all the 8 patients (male∶female=5∶3), the age of onset was 7 to 74 (40.4±7.4) years. Seven had adult-onset and 1 had juvenile-onset, with various types of onset symptoms, including progressive stiffness in lower limbs and walking difficulty, limb numbness, tremor, mental and behavioral abnormalities, cerebrovascular events, etc. Moderate to severe hyperhomocysteine (38.4-190.6 μmol/L) was present in all patients at first diagnosis. Among the 5 patients with cranial imaging examinations, all had white matter lesions. The genetic testing showed 7 patients with MTHFR gene pathogenic mutations (1 case with c.416C>T, and 6 cases with c.665C>T), and 1 patient with MMACHC gene pathogenic mutation (c.482G>A). Conclusions:Hereditary hyperhomocysteinemia is a metabolic disease, with complicated manifestations, varying degrees of severity, and diverse pathogenic genes. The cases with neurological involvement are not rare, such as spastic paraplegia-like manifestations, tremor, peripheral neuropathy, mental and behavioral abnormalities, cerebrovascular events.

Objective:To investigate the clinical, phenotypic and genotypic features of hereditary hyperhomocysteinemia mainly involving the nervous system.Methods:The clinical data, physical examination, imaging results, blood-urine tandem mass spectrometry analysis and genetic results of 8 patients with hyperhomocysteinemia from the Department of Neurology of the Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from September 2020 to December 2023 were collected, and the clinical, genetic features and pathogenic mechanisms of these patients were summarized and analyzed.Results:Among all the 8 patients (male∶female=5∶3), the age of onset was 7 to 74 (40.4±7.4) years. Seven had adult-onset and 1 had juvenile-onset, with various types of onset symptoms, including progressive stiffness in lower limbs and walking difficulty, limb numbness, tremor, mental and behavioral abnormalities, cerebrovascular events, etc. Moderate to severe hyperhomocysteine (38.4-190.6 μmol/L) was present in all patients at first diagnosis. Among the 5 patients with cranial imaging examinations, all had white matter lesions. The genetic testing showed 7 patients with MTHFR gene pathogenic mutations (1 case with c.416C>T, and 6 cases with c.665C>T), and 1 patient with MMACHC gene pathogenic mutation (c.482G>A). Conclusions:Hereditary hyperhomocysteinemia is a metabolic disease, with complicated manifestations, varying degrees of severity, and diverse pathogenic genes. The cases with neurological involvement are not rare, such as spastic paraplegia-like manifestations, tremor, peripheral neuropathy, mental and behavioral abnormalities, cerebrovascular events.

Objective:A nationwide multi-center and large sample survey was conducted to compare the validity of the Mini International Neuropsychiatric Interview (Hypo-) Manic Episode with Mixed Features-DSM-5 Module (MINI-M) questionnaire and the Clinically Useful Depression Outcome Scale Supplemented with Questions for the DSM-5 Mixed Features Specifier (CUDOS-M) depression subscale in identifying mixed features in patients experiencing (hypo-) manic episodes.Methods:Using a convenience sampling method, 366 patients with bipolar disorder experiencing acute (hypo-) manic episodes who met the inclusion and exclusion criteria were recruited. The diagnosis of "with mixed features" was based on the DSM-5 criteria for mixed features. The predictive validity of the MINI-M questionnaire and the CUDOS-M depression subscale to screen mixed features was analyzed using the receiver operating characteristic (ROC) curve. Additionally, the difference in area under the ROC curve (AUC) between the two instruments was compared.Results:The AUC for the MINI-M questionnaire and the CUDOS-M depression subscale in screening mixed features were 0.79 (95 %CI=0.75-0.84) and 0.81 (95 %CI=0.77-0.86), respectively. There was no statistically significant difference in AUC between the two measurements ( Z=-1.19, P>0.05). Among patients with acute (hypo-) manic episodes, 45.9% (168/366) presented with mixed features according to the DSM-5 criteria, while the corresponding figures were 43.7% (160/366) using the MINI-M questionnaire (total score≥3) and 42.1% (154/366) using the CUDOS-M depression subscale (total score≥20). Screening results were comparable among the three measures. Conclusion:Mixed features are common among patients experiencing acute (hypo-) manic episodes. The MINI-M questionnaire and the CUDOS-M depression subscale demonstrate equivalent validity in identifying mixed features.

Objective:A nationwide multi-center and large sample survey was conducted to compare the validity of the Mini International Neuropsychiatric Interview (Hypo-) Manic Episode with Mixed Features-DSM-5 Module (MINI-M) questionnaire and the Clinically Useful Depression Outcome Scale Supplemented with Questions for the DSM-5 Mixed Features Specifier (CUDOS-M) depression subscale in identifying mixed features in patients experiencing (hypo-) manic episodes.Methods:Using a convenience sampling method, 366 patients with bipolar disorder experiencing acute (hypo-) manic episodes who met the inclusion and exclusion criteria were recruited. The diagnosis of "with mixed features" was based on the DSM-5 criteria for mixed features. The predictive validity of the MINI-M questionnaire and the CUDOS-M depression subscale to screen mixed features was analyzed using the receiver operating characteristic (ROC) curve. Additionally, the difference in area under the ROC curve (AUC) between the two instruments was compared.Results:The AUC for the MINI-M questionnaire and the CUDOS-M depression subscale in screening mixed features were 0.79 (95 %CI=0.75-0.84) and 0.81 (95 %CI=0.77-0.86), respectively. There was no statistically significant difference in AUC between the two measurements ( Z=-1.19, P>0.05). Among patients with acute (hypo-) manic episodes, 45.9% (168/366) presented with mixed features according to the DSM-5 criteria, while the corresponding figures were 43.7% (160/366) using the MINI-M questionnaire (total score≥3) and 42.1% (154/366) using the CUDOS-M depression subscale (total score≥20). Screening results were comparable among the three measures. Conclusion:Mixed features are common among patients experiencing acute (hypo-) manic episodes. The MINI-M questionnaire and the CUDOS-M depression subscale demonstrate equivalent validity in identifying mixed features.

Objective:This study investigates the difference in the detection rate and symptomatology between ICD-10 and DSM-5 diagnostic criteria for bipolar disorder with mixed states.Methods:Based on the Phase Ⅰ (2012) and Phase Ⅱ (2021) databases of National Bipolar Mania Pathway Survey (BIPAS), patients with bipolar disorder were included. General demographic data, clinical characteristics, symptomatic phenotypes, and mixed characteristics were retrieved. The detection rates and symptomatic performances of patients with or without mixed states in Phase Ⅰ and Ⅱ were compared using the chi-square test.Results:For patients with mixed states, the detection rate during Phase Ⅱ (2021) using DSM-5 (18.79%, 199/1 059) criteria was significantly higher than that during Phase Ⅰ (2012) using ICD-10 (6.78%, 199/2 934; χ 2=125.05, P<0.001). Whether using ICD-10 or DSM-5 criteria, patients with mixed states had a significantly higher frequency of multiple symptomatic manifestations. Conclusion:The DSM-5 diagnostic criteria generate a high detection rate for bipolar disorder with mixed states. The clinical phenotypes of bipolar disorder with mixed states vary significantly using different diagnostic tools.

Objective:This study investigates the difference in the detection rate and symptomatology between ICD-10 and DSM-5 diagnostic criteria for bipolar disorder with mixed states.Methods:Based on the Phase Ⅰ (2012) and Phase Ⅱ (2021) databases of National Bipolar Mania Pathway Survey (BIPAS), patients with bipolar disorder were included. General demographic data, clinical characteristics, symptomatic phenotypes, and mixed characteristics were retrieved. The detection rates and symptomatic performances of patients with or without mixed states in Phase Ⅰ and Ⅱ were compared using the chi-square test.Results:For patients with mixed states, the detection rate during Phase Ⅱ (2021) using DSM-5 (18.79%, 199/1 059) criteria was significantly higher than that during Phase Ⅰ (2012) using ICD-10 (6.78%, 199/2 934; χ 2=125.05, P<0.001). Whether using ICD-10 or DSM-5 criteria, patients with mixed states had a significantly higher frequency of multiple symptomatic manifestations. Conclusion:The DSM-5 diagnostic criteria generate a high detection rate for bipolar disorder with mixed states. The clinical phenotypes of bipolar disorder with mixed states vary significantly using different diagnostic tools.

Objective:To evaluate the prognostic value of thromboelastography maximum amplitude(MA)and arterial blood lactate levels for sepsis in elderly patients.Methods:A retrospective analysis was performed on clinical data of 63 sepsis patients(≥60 years old)admitted to the Intensive Care Unit(ICU)of Bethune Hospital of Shanxi Province from December 2018 to February 2020.MA values, white blood cell counts, lymphocyte counts, platelets, acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)scores, sequential organ failure assessment(SOFA)scores, underlying diseases, body mass index, laboratory test results and other related treatments were analyzed.The subjects were divided into the survival group and the death group according to the 28-day survival outcome.Differences in MA, APACHE Ⅱ scores, SOFA scores and laboratory test results between the two groups were analyzed, and the correlations of MA with infection parameters and age were examined.Influencing factors of survival outcomes were analyzed using multivariate Logistic regression.The receiver operating characteristic curve(ROC)was used to calculate the prognostic value of MA and arterial lactate for sepsis in elderly patients.Results:The main sources of infections were pulmonary and abdominal(79.4%, 50/63)in 63 elderly patients with sepsis.The incidences of positive blood cultures and deaths were 15.9%(10/63)and 66.7%(42/63), respectively.There existed significant differences in lymphocyte counts, arterial lactate levels, MA and lengths of stay in the ICU between the survival group and the death group( t=3.847, 2.153, 2.745, -3.574, respectively, all P<0.05).MA was correlated with arterial lactate, SOFA score and survival outcome( r=-0.498, -0.506, and -0.358, respectively, all P<0.05).Multivariate Logistic regression analysis showed that MA and arterial lactate were independent factors for the survival outcome( OR=1.626, 0.766, all P<0.05).The area under the ROC curve(AUC, 95% CI)for the combination of MA and arterial lactate was larger than that of either MA or arterial lactate alone(0.89, range: 0.763-0.846; 0.58, range: 0.574-0.730; 0.77, range: 0.521-0.832; all P<0.05). Conclusions:The combination of thromboelastography maximum amplitude and lactate in arterial blood has important clinical value in assessing the prognosis of elderly patients with sepsis.

Objective:To screen lipid biomarker in sepsis patients with different survival outcome based on ultra high performance liquid chromatography-mass spectrometry(UHPLC-MS/MS) technique.Methods:From September 2019 to April 2020, 30 septic patients admitted in Department of Intensive Care Unit and 30 cases of physical examination at the same time in Shanxi Bethune Hospital were studied. Lipid metabolite in serum were detected by UHPLC-MS/MS technique. According to the 28 day survival outcome of sepsis patients, they were divided into survival group (21 cases) and death group (9 cases). The baseline data of case group and control group, survival group and death group were compared respectively. Independent sample t-test and orthogonal partial least squares discriminant analysis (OPLS-DA) were further performed to identify lipid biomarkers related to sepsis survival outcome. Receiver operating characteristic (ROC) curve to evaluate the predictive efficacy of differential lipids on the survival outcome of biomarker sepsis patients. Results:There were 32 lipid subclasses and 1 437 differential lipid molecules in the sepsis group compared with the control group. 196 differential lipid molecules in the sepsis survival group and the death group were screened according to the OPLS-DA model (variable weight of projection (VIP)>1), which were glycerophosphingolipids (129), sphingolipids (52), glycerides (14), and sterols (1).All the original data were statistically analyzed by univariate independent sample t-test. There were statistically significant differences in 15 lipid molecules between the two groups. Combined with VIP > 1 and P < 0.01, three lipid molecules were finally screened, which were sphingomyelin (SM) lipid molecules, SM (d30∶1), SM (d32∶2), SM (d32∶1). ROC curve analysis showed that the areas under curves of the above three lipid molecular were 0.915, 0.892, 0.898, respectively. The sensitivity was 77.27%, 95.45%,72.73%. The specificity was 100.0%, 87.5%,100.0%. Further Z-test showed that there was no significant difference in the area under the ROC curve ( Z(SM (d30∶1) and SM (d32∶1)) =0.36, P=0.722; Z(SM (d30∶1) and SM (d32∶2))=0.34, P=0.732; Z(SM (d32∶1) and SM (d32∶1))=0.07, P=0.942). Conclusions:Sphingomyelin may be involved in the formation of different clinical outcomes of sepsis, and has a good predictive effect on the survival outcome of sepsis.

Objective　To explore the effects of ox-LDL on the biosynthesis of resolving D2 (RvD2) by human periphery blood mononuclear cells (PBMCs)-derived macrophages in ischemic stroke (IS).Methods　Matured macrophages were derived from PBMCs of ischemic stroke patients and healthy controls,and were grouped to vehicle group and oxidized low-density lipoprotein (ox-LDL) group.We compared the level of RvD2,15-lipoxygenase (15-LOX) and 5-lipoxygenase (5-LOX),as well as G-protein coupled receptor 18 (GPR18).between groups,and determined the formation of foam cells.Results　Compared with vehicle group,the level of RvD2(P<0.001),15-LOX and GPR18(P<0.05) in ox-LDL stimulated group was significantly increased,however,no significant difference in the expression of 5-LOX between ox-LDL and vehicle group was observed.After ox-LDL stimulation,compared with healthy control,elevation of RvD2 synthesis in ischemic stroke group was significantly lower（P<0.05）,and foam cell formation was also more severe in macrophages of stroke patients.Conclusion　Ox-LDL stimulates biosynthesis of RvD2 by human macrophage,perhaps through enhancing 15-LOX expression.Moreover,function of increasing RvD2 synthesis upon ox-LDL stimulation is impaired in stroke patients.

Objective:This study aims to investigate the prevalence and distribution characteristics of mental disorders among people aged 18 and above in Shandong Province.Methods:In 2015, an epidemiological survey was carried out to investigate the patterns of mental disorders in 49 counties of Shandong Province. A total of 28 000 individuals aged 18 years or older were selected using the multistage stratified cluster sampling method. All these participants were classified as at a high or low risk of mental disorders according to the assessment results of the revised version of the General Health Questionnaire (GHQ). The diagnosis of mental disorders was confirmed using the Structured Clinical Interview for Diagnostic and Statistical Manual, Forth edition (DSM-Ⅳ) axis I or MMSE. All participants at high risk of mental disorders were evaluated using DSM-Ⅳ or MMSE to confirm the psychiatric diagnoses, while 10% of participants at low risk of mental disorders were randomly selected to be evaluated. The prevalence and its 95% confidence interval of mental disorders were adjusted according to study design and sociodemographic characteristics of the sample. The between-group differences of prevalence were compared using chi-square tests or Fisher′s exact tests as appropriately.Results:A total of 27 489 individuals completed survey. The adjusted prevalence of any mental disorder was 17.46% (95 %CI 17.02%-17.89%). The five most prevalent mental disorder spectrums were substance use disorders (5.29%), mood disorders (4.47%), anxiety disorders (4.46%), intellectual and mental disorders due to physical or substance (1.91%), and psychotic disorders (1.12%). The most common mental disorders were alcohol use disorder (5.27%) and major depressive disorder (2.14%). The prevalence of mental disorders in men was higher than that in women (23.37% vs. 13.89%; χ 2=408.91, P<0.01). There was no significant difference in the prevalence of mental disorders between rural residents and urban residents (17.69% vs. 17.20%; χ2=1.05, P=0.305). Of participants with mental disorders, 26.12% (1 047/4 008) had moderate to severe functional impairment and 10.98% (428/3 898) have sought professional help. Conclusion:The prevalence of mental disorders among people aged 18 and above in Shandong Province is basically consistent with the results of similar domestic studies. The prevalence of mental disorder was higher in men than in women and was not differ in participants living in urban and rural areas. Alcohol use disorder, major depressive disorder, non-specific anxiety disorder and non-specific depressive disorder are most common mental disorders.