Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It is highly contagious and can cause death in severe cases. As reported by the World Health Organization (WHO), as of 6:36 pm Central European Summer Time (CEST), 12 August 2022, there had been 585 950 285 confirmed cases of COVID-19, including 6 425 422 deaths (WHO, 2022).
Humans ; COVID-19 ; SARS-CoV-2 ; Mental Health ; Cohort Studies ; Quality of Life ; China/epidemiology* ; Health Personnel ; Hospitals ; Lung

Objective:To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c. 609G>A homologous variant. Methods:A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164patients of cblC type with MMACHC c. 609G>A homologous variant was conducted.The patients were diagnosed by biochemical and genetic analysisfrom January 1998 to December 2020. Results:Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated fromthe age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance ( P<0.05). Conclusion:Most of the patients with MMACHC c. 609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.

Objective:To analyze the clinical features and CBS gene variants of 13 patients with classic homocystinuria, and the strategies of individual treatment and prevention were explored.Methods:The general information, clinical manifestations, laboratory tests, cranial images, CBS gene variants, diagnosis and therapeutic strategies of 13 patients with classic homocystinuria admitted to the Department of Pediatrics of Children′s Hospital Affiliated to Zhengzhou University and Peking University First Hospital from November 2013 to June 2021 were analyzed retrospectively.Results:There were 13 patients diagnosed at the age of 10 days to 14 years, 6 were male and 7 were female. There were 3 patients detected by newborn screening and received treatment at the asymptomatic stage. There were 10 patients clinically diagnosed at the age of 5 to 14 years. Their symptoms appeared at age of 1 to 6 years. The major clinical manifestations were marfanoid features, lens dislocation and (or) myopia, developmental delay, osteoporosis, and cardiovascular diseases. Brain magnetic resonance imaging showed asymmetric infarcts in 4 patients and hypomyelination in 1 case. Increased blood methionine, plasma total homocysteine and urinary total homocysteine with normal urinary methylmalonic acid were found in 13 patients. The biochemical features were consistent with classic homocystinuria. Totally 18 variants were identified in CBS gene of 13 patients, 10 variants were novel and 8 were reported. only 1 patient was partially responsive to vitamin B 6 treatment, while 12 cases were non-responsive. They were mainly treated with low methionine diet and betaine supplement. Three vitamin B 6 non-responsive cases received liver transplantation at age of 3, 8 and 8 years, respectively. Their blood methionine and total homocysteine returned to normal within a week after liver transplantation. One patient died. Prenatal diagnosis was performed for a fetus when the mother was pregnant again. Two pathogenic CBS gene variants were identified from the amniocytes as same as the proband. Conclusions:The clinical manifestations of classic homocystinuria are complex and variable. Blood amino acid analysis, serum or urine total homocysteine assay and gene analysis are critical for its diagnosis. There were 10 novel CBS gene varients were identified expanding the CBS gene varient spectrum. Liver transplantation is an effective treatment. Prenatal diagnosis is important to prevent classic homocysteinuria.

Diagnosis, Differential ; Humans ; Lung Neoplasms/genetics* ; Neoplasm Metastasis ; Neoplasms, Multiple Primary/diagnosis*

Objective:To analyze the clinical features, genetic characteristics, treatment and follow-up results of patients with hydrocephalus caused by methylmalonic acidemia combined with homocysteinuria, and to discuss the optimal strategies for assessing and treating such patients.Methods:From January 1998 to December 2020, 76 patients with hydrocephalus due to methylmalonic acidemia combined with homocysteinuria in the Department of Pediatrics in 11 hospitals including Peking University First Hospital were diagnosed by biochemical, genetic analysis and brain imaging examination. The patients were divided into operation-group and non-operation-group according to whether they underwent ventriculoperitoneal shunt. The clinical features, laboratory examinations, genotype, and follow-up data were retrospectively analyzed. Data were compared between the two groups using rank sum test, and categorical data were compared using χ 2 test. Results:Among the 76 patients (51 male, 25 female), 5 were detected by newborn screening, while 71 were diagnosed after clinical onset, 68 cases (96%) had early-onset, 3 cases (4%) had late-onset. The most common clinical manifestations of 74 cases with complete data were psychomotor retardation in 74 cases (100%), visual impairment in 74 cases (100%), epilepsy in 44 cases (59%), anemia in 31 cases (42%), hypotonia or hypertonia in 21 cases (28%), feeding difficulties in 19 cases (26%) and disturbance of consciousness in 17 cases (23%). Genetic analysis was performed in 76 cases, all of whom had MMACHC gene variations, including 30 homozygous variations of MMACHC c.609G>A. The most common variations were c.609G>A (94, 62.7%), followed by c.658_660del (18, 12.0%), c.567dupT (9, 6.0%) and c.217C>T (8, 5.3%). Therapy including cobalamin intramuscular injection, L-carnitine and betaine were initiated immediately after diagnosis. A ventriculoperitoneal shunt operation was performed in 41 cases (operation group), and 31 patients improved after metabolic intervention (non-operation group). There was no significant difference in the age of onset, the age of diagnosis, the blood total homocysteine, methionine, and urinary methylmalonic acid concentration between the two groups (all P>0.05). The symptoms of psychomotor development, epilepsy, and visual impairments improved gradually after a long-term follow-up in the operation group. Conclusions:Hydrocephalus is a severe complication of methylmalonic acidemia combined with homocysteinuria. The most common clinical manifestations are psychomotor retardation, visual impairment, and epilepsy. It usually occurs in early-onset patients. Early diagnosis and etiological treatment are very important. Hydrocephalus may improve after metabolic intervention in some patients. For patients with severe ventricular dilatation, prompt surgical intervention can improve the prognosis.

Objective To assess the risk of public health incidents in the Hankou River Beach during the 7th World Military Games, and to provide reference for risk early warning and emergency preparedness. Methods An expert consultation meeting was held to determine the evaluation index and risk scores. Based on the Kaiser model, a public health risk assessment system suitable for Hankou River Beach was established, and the risk value of each risk event was calculated by the method of risk value calculation. The risk matrix method was used to evaluate the risk levels of different risk events in different areas of Hankou River Beach. Then, according to the calculated Borda values and order values of risk events in different regions, the different risks were ranked in each area. Results The calculation revealed that the risk values of schistosomiasis in the first, second, third and fourth stages of the river beach were 8.43%, 14.68%, 25.26% and 27.56%, respectively; the risk values of vector infectious diseases in each stage were 13.42%, 16.40%, 18.67% and 19.22%; the risk values of accidental injury and other events were 20.34%, 22.94%, 19.00% and 16.53%. According to the risk matrix, the first and second stages of schistosomiasis and vector borne infectious diseases, as well as the fourth stage of accidental injuries were located in the low-risk zone, while the other risk events were in the medium risk zone. The ranking results of Borda sequence value showed that the highest risk public health events in the first and second phases of the river beach were accidental injuries and others, in the third phase was schistosomiasis and accidental injuries, and in the fourth phase was schistosomiasis. Conclusion Considering the results of each evaluation method, the public health events with the highest risk in phase I and phase II of the river beach were accidental injuries, while in phase III and phase IV were schistosomiasis. It is suggested that relevant departments should formulate different strategies and take targeted measures to ensure the public health and safety of Hankou river beach during the Military Games.

Objective:To explore the clinical characteristics, plasma levels of hydrogen sulfide(H 2S) and the relationship between the genotype and phenotype of cardiovascular involvement in children with methylmalonic acidemia and homocystinemia. Methods:The clinical and laboratory data of 66 outpatients diagnosed with methylmalonic acidemia combined with homocystinemia in Department of Pediatrics, Peking University First Hospital from January 2014 to July 2014 were collected and analyzed respectively, and the patients were divided into 2 groups: cardiovascular involvement group (10 cases) and non-cardiovascular involvement group(56 cases). The differences in the clinical characteristics, plasma levels of H 2S and genotypes were compared between 2 groups. Results:(1) There were 45 cases of early-onset children under 1 year old, including 4 cases of cardiovascular system involvement and 41 cases of non-cardiovascular system involvement.Twenty-one cases had onset above 1 year old, including 6 cases of cardiovascular system involvement and 15 cases of non-cardiovascular system involvement. There were 44 male children, including 8 cases with cardiovascular system involvement and 36 cases without cardiovascular system involvement; 22 cases female children, including 2 cases with cardiovascular system involvement and 20 cases without cardiovascular system involvement. There was no significant difference in onset age and gender distribution between the 2 groups ( χ2=2.910, 0.368, all P>0.05). (2)In the 10 cases with cardiovascular involvement, there were 3 cases with hypertension, 2 cases with hypertension combined with pulmonary hypertension, 2 cases with mild myocardial hypertrophy, 1 case with atrial septal defect combined with pulmonary hypertension, 1 case with pulmonary hypertension, 1 case with myocardial noncompaction.Compared with the non-cardiovascular involvement group, the proportion of kidney involvement was increased and that of nervous system was decreased in cardiovascular system involvement group( χ2=20.34, 5.79, all P<0.05), the proportion of hematological system involvement between the 2 groups had no significant differences ( χ2=1.28, P>0.05). The plasma levels of hydrogen sulfide of children with cardiovascular involvement was significantly lower than that of non-cardiovascular involvement[(33.8±3.6) μmol/L vs.(39.3±5.2) μmol/L, t=-3.22, P<0.01]. (3) MMACHC gene mutation (cblC type) was identified in all 46 patients.It was found that the most common type of gene mutation was c. 80A>G in cardiovascular involvement group, while c. 609G>A was the most common type of gene mutation in non-cardiovascular involvement group. Conclusions:The clinical manifestations of children with methylmalonic acidemia and homocystinemia involving cardiovascular system are multiple and prone to multiple system involvement, especially renal involvement.A decrease in plasma hydrogen sulfide levels may be involved in the involvement of its cardiovascular system.The MMACHC gene c. 80A>G mutation is the most common genetic mutation site in children with cardiovascular involvement with methylmalonic acidemia and homocystinemia.

Objectives:To summarize the clinical and genetic characteristics of the patients with isolated methylmalonic acidemia and investigate the strategies for the diagnosis, treatment and prevention.Methods:Three hundred and fourteen patients (180 males, 134 females) with isolated methylmalonic acidemia were ascertained from 26 provinces or cities across the mainland of China during January 1998 to March 2020. Genetic analysis was performed by Sanger sequencing, gene panel sequencing, whole exome sequencing, multiplex ligation-dependent probe amplification or quantitative PCR. According to the age of onset, the patients were divided to early-onset group (≤12 months of age) and the late-onset group (>12 months of age). They were treated by cobalamin, L-carnitine and (or) special diet and symptomatic treatment. Statistical analysis was done using Chi-square test.Results:Fifty-eight of 314 (18.5%) patients were detected by Newborn screening using liquid chromatography tandem mass spectrometry. Five cases (1.6%) had a postmortem diagnosis. Two hundred and fifty-one patients (79.9%) were clinically diagnosed with an age of onset ranged from 3 hours after birth to 18 years. One hundred and fifty-nine patients (71.0%) belonged to early-onset groups, 65 patients (29.0%) belonged to the late-onset group. The most common symptoms were metabolic crises, psychomotor retardation, epilepsy, anemia and multiple organ damage. Metabolic acidosis and anemia were more common in early-onset patients than that in late-onset patients (20.8%(33/159) vs. 9.2% (6/65), 34.6% (55/159) vs. 16.9% (11/165), χ 2=4.261, 6.930, P=0.039, 0.008). Genetic tests were performed for 236 patients (75.2%), 96.2%(227/236) had molecular confirmation. One hundred and twenty-seven variants were identified in seven genes (MMUT, MMAA, MMAB, MMADHC, SUCLG1, SUCLA2, and MCEE), of which 49 were novel. The mut type, caused by the deficiency of methylmalonyl-CoA mutase, was the most common ( n=211, 93%) cause of this condition. c.729_730insTT, c.1106G>A and c.914T>C were the three most frequent mutations in MMUT gene. The frequency of c.914T>C in early-onset patients was significantly higher than that in late-onset patients (8.3% (18/216) vs. 1.6% (1/64), χ 2=3.859, P=0.037). Metabolic crisis was more frequent in mut type than the other types (72.6% (114/157) vs. 3/13, χ 2=13.729, P=0.001),developmental delay and hypotonia were less frequent in mut type (38.2% (60/157) vs. 9/13, 25.5% (40/157) vs. 8/13, χ 2=4.789, 7.705, P=0.030, 0.006). Of the 58 patients identified by newborn screening, 44 patients (75.9%) who were treated from asymptomatic phase developed normally whereas 14 patients (24.1%) who received treatment after developing symptoms exhibited varying degrees of psychomotor retardation. Conclusions:The characteristics of phenotypes and genotypes among Chinese patients with isolated methylmalonic acidemia were analyzed. Expanded the mutation spectrum of the associated genes. Because of the complex clinical manifestations and severe early onset of isolated methylmalonic acidemia, Newborn screening is crucial for early diagnosis and improvement of prognosis. MMUT gene is recommended for carrier screening as an effort to move the test earlier as a part of the primary prevention of birth defects.

Objective: To analyz the current situation of the diagnosis, treatment and prevention of methylmalonic acidemia, the phenotypes, biochemical features and genotypes of the patients in the mainland of China, were investigated. Methods: Tottally 1 003 patients of methylmalonic acidemia from 26 provinces and municipalities of the mainland of China were enrolled. The clinical data, biochemical features and gene mutations were studied. Blood aminoacids and acylcarnitines, urine organic acids, and plasma total homocysteine were determined for the biochemical diagnosis. Gene analyses were performed for the genetic study of 661 patients. The patients were treated with individual intervention and long-term follow up. Prenatal diagnoses were carried out for 165 fetuses of the families. Results: Among 1 003 patients (580 boys and 423 girls), 296 cases (29.5%) had isolated methylmalonic acidemia; 707 cases (70.5%) had combined homocysteinemia; 59 patients (5.9%) were detected by newborn screening; 944 patients (94.1%) had the onset at the ages from several minutes after birth to 25 years and diagnosed at 3 days to 25 years of age. The main clinical presentations were psychomotor retardation and metabolic crisis. Multi-organ damage, including hematological abnormalities, pulmonary hypertension, kidney damage, were found. MMACHC, MUT, MMAA, MMAB, HCFC1, SUCLG1, SUCLA2 mutations were found in 631 patients (96.6%) out of 661 patients who accepted gene analysis. MMACHC mutations were detected in 460 patients (94.7%) out of 486 cases of methylmalonic acidemia combined with homocysteinemia. MUT mutations were found in 158 (90.3%) out of 169 cases of isolated methylmalonic acidemia. The development of 59 patients detected by newborn screening were normal; 918 cases (97.2%) were diagnosed after onset accepted the treatment. Forty-five of them completely recovered with normal development. Twenty-six patients (2.7%) died; 873 (92.5%) patients had mild to severe psychomotor retardation. Methylmalonic acidemia were found in 35 out of 165 fetuses by metabolites assay of amniotic fluid and amniocytes gene analysis. Conclusion Combined methylmalonic acidemia and homocysteinemia is the common type of methylmalonic acidemia in the mainland of China. CblC defect due to MMACHC mutations is the most common type of methylmalonic acidemia combined with homocysteinemia. MUT gene mutations are frequent in the patients with isolated methylmalonic acidemia. Newborn screening is key for the early diagnosis and the better outcome. Combined diagnosis of biochemical assays and gene analysis are reliable for the prenatal diagnosis of methylmalonic acidemia.

Objective To investigate the effectiveness of Varenicline combined with MEDCHART application software for health education and follow-up in patients at smoking cessation clinic.Methods A total of 104 cases who had smoking cessation counseling and intervention at smoking cessation clinic from February 2014 to January 2015 were divided randomly into MEDCHART APP group (n=51) and conventional group (n=53).Both groups were intervened by brief admonishment and given Varenicline.The 9-12 weeks and 26th week protracted continuous abstinence rates were observed.Results There were no significant difference in 9-12 week protracted withdrawal rate between 26th week APP and conventional groups (56.9％ vs.45.3％),the 26th week abstinence rates in group MEDCHART APP (41.2％) were significantly higher than the conventional group (20.8％)(x2=5.088,P＜0.05).There was significant difference in full course completion rates between the two groups;15 cases (29.4％) completed the course in group MEDCHART APP,whereas 5 cases (9.4％) did so in conventional group (x2=4.405,P＜0.05).Conclusion MEDCHART APP can strengthen health education and follow-up,which helps extend the time for Varenicline,increase 26th week smoking cessation withdrawal rate.It is a useful tool for smoking cessation education and follow-up.