[Subphenotypes and precision medicine in acute respiratory distress syndrome].

The presence of significant complex heterogeneity among patients with acute respiratory distress syndrome (ARDS) is a major reason for the failure of drug treatments. Precision medicine seeks to elucidate the potential mechanisms of ARDS heterogeneity, define subtypes of ARDS patients with specific characteristics, and rapidly identify the patient groups most likely to benefit from targeted treatments, thereby maximizing treatment efficiency and minimizing adverse reactions. This review discusses on the current state of research on ARDS subtypes from multiple perspectives, including etiology, onset time, radiology, pathology, oxygenation index, respiratory mechanics, protein biomarkers, genetics, transcriptomics, and microbiomics, with the aim of deepening the understanding of the pathogenesis of ARDS and thereby guiding precision treatment of ARDS.

[Epidemiological characteristics of severe fever with thrombocytopenia syndrome in China, 2018-2021].

Objective: To understand the epidemiological characteristics and incidence trend of severe fever with thrombocytopenia syndrome (SFTS) in China. Methods: The incidence data of SFTS in China from 2018 to 2021 were collected from Chinese Disease Prevention and Control Information System for a statistical and descriptive epidemiological analysis by using software such as Excel 2016, Joinpoint 5.0.2, SPSS 26.0, and GraphPad Prism 8.0, especially, the SFTS cases reported monthly by key provinces were analyzed. Results: From 2018 to 2021, a total of 8 835 SFTS cases were reported in 25 provinces and the annual incidence showed an upward trend. The distribution of SFTS cases showed clustering, but the cases were mainly sporadic ones. The cases began to increase in March, mainly occurred during April to October (96.79%,8 551/8 835), and peaked during May to July. The cases were mainly distributed in middle-aged and old farmers, and slight more cases were women. The average case fatality rate was 5.38%, which varied greatly with areas. The case fatality rate tended to increase with age. Conclusion: From 2018 to 2021, the epidemiological characteristics of SFTS in China remained stable, but the number of reported cases gradually increased and the distribution showed an expanding trend, to which close attention should be paid.

[Monitoring and analysis on host animals of hemorrhagic fever with renal syndrome in Henan Province from 2019 to 2022].

Objective: To investigate the distribution and hantavirus (HV) carrying state in host animals of hemorrhagic fever with renal syndrome (HFRS) in Henan Province from 2019 to 2022. Methods: Host animal monitoring was carried out at the monitoring sites of HFRS in Henan Province. The real-time fluorescence quantitative PCR was used to detect hantavirus in rat lungs. The types of hantavirus were analyzed. The positive samples were sequenced and then sequence homology and variation were analyzed. Results: A total of 1 308 rodents were captured from 2019 to 2022, 16 specimens of rat lungs tested positive for hantavirus nucleic acid. The positive rate of HV was 1.22% (16/1 308). According to type, the positive rate of HV in Apodius agrarius was the highest (68.75%, 11/16). According to distribution, the positive rate of HV in field samples was the highest (2.50%, 12/480), and the positive rate of HV in residential samples was 0.53% (4/759). The typing results of 16 positive samples showed that all viruses were hantavirus type Ⅰ (hantaan virus). The positive samples were sequenced and eight S gene fragments (GenBank number: OQ681444-OQ681451) and six M gene fragments (OQ681438-OQ681443) were obtained. The S and M gene fragments were similar to the Shaanxi 84FLi strain and Sichuan SN7 strain. Phylogenetic analysis of S and M gene fragments showed that they all belonged to the hantaan virus-H5 subtype. Amino acid sequence analysis revealed that, compared with the hantaan virus vaccine strain 84FLi, the 74th amino acid encoded by eight S fragments was replaced by aspartamide with serine. Tryptophan was replaced by glycine at the 14th position of Gn region in XC2022047, and isoleucine was replaced by alanine at the 359 position of XC2022022 and XC2022024. Conclusion: The hantavirus carried by host animals in Henan Province from 2019 to 2022 belongs to the type Ⅰ (hantaan virus), and Apodemus agrarius is still the dominant host animal of the hantaan virus. Compared with the vaccine strains, amino acid sites are replaced in the immune epitopes of the S and M gene fragments.

Characterization of the complete mitochondrial genome of Acanthogyrus (Acanthosentis) bilaspurensis Chowhan, Gupta & Khera, 1987 (Eoacanthocephala: Quadrigyridae), the smallest mitochondrial genome in Acanthocephala, and its phylogenetic implications.

The phylum Acanthocephala is an important group of parasites with more than 1,300 species parasitizing intestine of all major vertebrate groups. However, our present knowledge of the mitochondrial genomes of Acanthocephala remains very limited. In the present study, we sequenced and annotated the complete mitochondrial genome of Acanthogyrus (Acanthosentis) bilaspurensis (Gyracanthocephala: Quadrigyridae) for the first time based on the specimens recovered from the intestine of common carp Cyprinus carpio Linnaeus (Cyprinidae) in Pakistan. The mitochondrial genome of A. bilaspurensis is 13,360 bp in size and contains 36 genes, representing the smallest mitogenome of acanthocephalans reported so far. The mitogenome of A. bilaspurensis also has the lowest level of overall A+T contents (59.3%) in the mitogenomes of Eoacanthocephala, and the non-coding region 3 (NCR3) lies between trnS2 and trnI, which is different from all of the other acanthocephalan species. Phylogenetic analyses based on concatenating the amino acid sequences of 12 protein-coding genes using maximum likelihood (ML) and Bayesian inference (BI) methods revealed that the family Pseudoacanthocephalidae is a sister to the Arhythmacanthidae rather than the Cavisomatidae, and the families Rhadinorhynchidae and Cavisomatidae showed sister relationships.

[The epidemiology and pathogeny investigation of two clusters of severe fever with thrombocytopenia syndrome disease outbreaking in Henan Province, 2022].

To investigate two clusters of severe fever with thrombocytopenia syndrome virus (SFTSV) in Xinyang City, Henan Province, in 2022, and analyze their causes, transmission route, risk factors, and the characteristics of virus genetic variation. Case search and case investigation were carried out according to the case definition. Blood samples from cases, family members and neighbors and samples of biological vectors were collected for RT-PCR to detect SFTSV. The whole genome sequencing and bioinformatics analysis were performed on the collected positive samples. A total of two clustered outbreaks occurred, involving two initial cases and ten secondary cases, all of which were family recurrent cases. Among them, nine secondary cases had close contact with the blood of the initial case, and it was determined that close contact with blood was the main risk factor for the two clustered outbreaks. After genome sequencing analysis, we found that the SFTSV genotype in two cases was type A, which was closely related to previous endemic strains in Xinyang. The nucleotide sequence of the SFTSV in the case was highly homologous, with a total of nine amino acid mutation sites in the coding region. It was not ruled out that its mutation sites might have an impact on the outbreak of the epidemic.

[Epidemiological characteristics and analysis of related infection risk factors for influenza in Anhui Province from 2013 to 2021].

Objective: Analysis of the characteristics of influenza epidemic in Anhui Province and quantification of the impact of different factors on influenza occurrence, providing scientific basis for better influenza prevention and control. Methods: Descriptive analysis and factor analysis were conducted on influenza-like illness (ILI) cases and RT-PCR results in Anhui Province from 2013 to 2021 using data from China's Influenza Monitoring Information System. Results: The percentage of influenza-like illness (ILI%) of sentinel hospitals in Anhui Province from April 1, 2013 to March 31, 2021 was 3.80% (1 209 142/31 779 987), showing an overall increasing trend, with a relatively high proportion in 2017-2018 at 4.30% (191 148/4 448 211). The proportion of ILI cases in infants and young children aged 0-4 years was a relatively high at 54.14% (654 676/1 209 142), and the highest ILI% was observed in Fuyang City, Anhui Province (6.25%, 236 863/3 788 863). Laboratory monitoring results showed that the positive rate of ILI cases in sentinel hospitals in 8 influenza monitoring years was 16.38% (34 868/212 912), showing an increasing trend year by year, with a relatively proportion in 2017-2018 at 26.19% (6 936/26 488). The detection rate of school-age children aged 5-14 years was a relativelyhigh at 28.81% (13 869/48 144), and the positive rate was a relatively high in Wuhu City among the 16 cities, reaching 22.01% (2 693/122 237). Influenza activity showed a single peak in winter-spring and alternating double peaks in winter-spring and summer, with different subtypes alternating, and A (H3N2) was the dominant subtype in summer. The results of a multiple logistic regression model showed that the positive rate was higher in 2017-2018, among children aged 5-14 years, in winter, and in southern Anhui. Conclusions: Influenza epidemic in Anhui Province has a clear seasonal pattern, and the ILI% and detection rate have shown an upward trend from 2013 to 2021. Therefore, it is suggested to ensure vaccine supply before the winter-spring influenza season arrives, and to strengthen vaccine uptake and health education to avoid the risk of infection during the peak period of influenza.

[Molecular genetic characteristics of a family which coinheritance of rare-88 C>G (HBB:c.-138 C>G) ß-thalassemia mutation with α-thalassemia and review of the literature].

The molecular genetic characteristics of a family with rare -88 C>G (HBB: c.-138 C>G) ß-thalassemia gene mutation were studied using cohort study. The cohort study was conducted from June to August 2022 by Prenatal Diagnosis Center of Sanya Women and Children's Hospital Managed by Shanghai Children's Medical Center. The phenotype and genotype were analyzed by hematological cytoanalyzer, automatic electrophoretic analysis system, and next-generation sequencing (NGS). And then, Sanger sequencing was used to verify the rare gene results. The results showed that the proband, her father, her uncle and her younger male cousin had discrete microcytosis (MCV 70.1 fl, 71.9 fl, 73.1 fl and 76.6 fl, respectively) and hypochromia (MCH 21.5 pg,22.0 pg,22.6 pg and 23.5 pg, respectively), elevated hemoglobin A2 level (5.3%, 5.4%, 5.4% and 5.5%, respectively), slightly elevated or normal fetal hemoglobin (Hb F), but no anemia. The proband was identified to have co-inherited ɑ-thalassemia (Hb Westmead gene heterozygous mutation, ɑwsɑ/ɑɑ) and ß-thalassemia with a rare -88 C>G (HBB: c.-138 C>G) heterozygous mutation (ß-88 C>G/ßN). Her mother had the same α-thalassemia as the proband. Her father, her uncle and her younger male cousin had the same rare -88 C>G heterozygous mutations as the proband. While her grandmother and younger brother were not carrier of thalassemia. In conclusion, 4 cases of rare -88 C>G(HBB:c.-138 C>G) heterozygous mutation had been detected in a Chinese family. Carriers of this beta-thalassemia are clinically asymptomatic. This study enriches the knowledge of the thalassemia mutation spectrum in Chinese people and provides valuable information for genetic counseling, prenatal diagnosis, and prevention of thalassemia, providing a scientific basis for improving the quality of birth population and preventing birth defects.

Emergent Majorana zero-modes in an intrinsic anti-ferromagnetic topological superconductor Mn2B2 monolayer.

Topological superconductors (TSCs) are an exotic field due to the existence of Majorana zero-modes (MZM) in the edge states that obey non-Abelian statistics and can be used to implement topological quantum computations, especially for two-dimensional (2D) materials. Here we predict manganese diboride (Mn2B2) as an intrinsic 2D anti-ferromagnetic (AFM) TSC based on the magnetic and electronic structures of Mn and B atoms. Once Mn2B2 ML enters a superconducting state, MZM will be induced by the spin-polarized helical gapless edge states. The Z2 topological non-trivial properties are confirmed by Wannier charge centers (WCC) and the platform of the spin Hall conductivity near the Fermi level. Phonon-electron coupling (EPC) implies s-wave superconductivity and the critical temperature (Tc) is 6.79 K.

Transcriptomic response of bioengineered human cartilage to parabolic flight microgravity is sex-dependent.

Spaceflight and simulated spaceflight microgravity induced osteoarthritic-like alterations at the transcriptomic and proteomic levels in the articular and meniscal cartilages of rodents. But little is known about the effect of spaceflight or simulated spaceflight microgravity on the transcriptome of tissue-engineered cartilage developed from human cells. In this study, we investigate the effect of simulated spaceflight microgravity facilitated by parabolic flights on tissue-engineered cartilage developed from in vitro chondrogenesis of human bone marrow mesenchymal stem cells obtained from age-matched female and male donors. The successful induction of cartilage-like tissue was confirmed by the expression of well-demonstrated chondrogenic markers. Our bulk transcriptome data via RNA sequencing demonstrated that parabolic flight altered mostly fundamental biological processes, and the modulation of the transcriptome profile showed sex-dependent differences. The secretome profile analysis revealed that two genes (WNT7B and WNT9A) from the Wnt-signaling pathway, which is implicated in osteoarthritis development, were only up-regulated for female donors. The results of this study showed that the engineered cartilage tissues responded to microgravity in a sex-dependent manner, and the reported data offers a strong foundation to further explore the underlying mechanisms.

[Analysis of the whole genome traceability and transmission path simulation experiment of the local cluster COVID-19 epidemic].

Objective: To trace and characterize the whole genome of SARS-CoV-2 of confirmed cases in the outbreak of COVID-19 on July 31, 2021 in Henan Province. Method: Genome-wide sequencing and comparative analysis were performed on positive nucleic acid samples of SARS-CoV-2 from 167 local cases related to the epidemic on July 31, 2021, to analyze the consistency and evolution of the whole genome sequence of virus. Results: Through high-throughput sequencing, a total of 106 cases of SARS-CoV-2 whole genome sequences were obtained. The results of genome analysis showed that the whole genome sequences of 106 cases belonged to the VOC/Delta variant strain (B.1.617.2 clade), and the whole genome sequences of 106 cases were shared with the genomes of 3 imported cases from Myanmar admitted to a hospital in Zhengzhou. On the basis of 45 nucleotide sites, 1-5 nucleotide variation sites were added, and the genome sequence was highly homologous. Conclusion: Combined with the comprehensive analysis of viral genomics, transmission path simulation experiments and epidemiology, it is determined that the local new epidemic in Henan Province is caused by imported cases in the nosocomial area, and the spillover has caused localized infection in the community. At the same time, it spills over to some provincial cities and results in localized clustered epidemics.

[Phenotypes and genotypes of 78 patients with propionic acidemia].

Objective: Propionic acidemia is a rare inherited metabolic disorder caused by propionyl CoA carboxylase (PCC) deficiency. This study aims to analyze the clinical characteristics and gene variations of Chinese patients with propionic acidemia, and to explore the correlation between clinical phenotypes and genotypes. Methods: Single-center, retrospective and observational study. Seventy-eight patients of propionic acidemia (46 males and 32 females) from 20 provinces and autonomous regions were admitted from January 2007 to April 2022. Their age of initial diagnosis ranged from 7 days to 15 years. The clinical manifestations, biochemical and metabolic abnormalities, genetic variations, diagnosis, treatment and outcome were studied. Chi-Square test or Mann-Whitney U test were used for statistical analysis. Results: Among 78 cases, 6 (7.7%) were identified by newborn screening; 72 (92.3%) were clinically diagnosed after onset, and the age of onset was 2 hours after birth to 15 years old; 32 cases had early-onset disease and 40 cases had late-onset disease. The initial manifestations included lethargy, hypotonia, vomiting, feeding difficulties, developmental delay, epilepsy, and coma. Among the 74 cases who accepted gene analysis, 35 (47.3%) had PCCA variants and 39 (52.7%) had PCCB variants. A total of 39 PCCA variants and 32 PCCB variants were detected, among which c.2002G>A and c.229C>T in PCCA and c.838dupC and c.1087T>C in PCCB were the most common variants in this cohort. The variants c.1228C>T and c.1283C>T in PCCB may be related to early-onset type. The variants c.838dupC, c.1127G>T and c.1316A>G in PCCB, and c.2002G>A in PCCA may be related to late-onset disease. Six patients detected by newborn screening and treated at asymptomatic stage developed normal. The clinically diagnosed 72 cases had varied complications. 10 (12.8%) cases of them died. 62 patients improved after metabolic therapy by L-carnitine and diet. Six patients received liver transplantation because of recurrent metabolic crisis. Their clinical symptoms were markedly improved. Conclusion: The clinical manifestations of propionic acidemia are complex and lack of specificity. Newborn screening and high-risk screening are keys for early treatment and better outcome. The correlation between the genotype and phenotype of propionic acidemia is unclear, but certain variants may be associated with early-onset or late-onset propionic acidemia.

[Clinical characteristics and CBS gene analysis of 13 cases with classic homocystinuria].

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 B6 treatment, while 12 cases were non-responsive. They were mainly treated with low methionine diet and betaine supplement. Three vitamin B6 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.

Transition from spin glass to paramagnetism in the magnetic properties of PrAu2Si2.

It is unexpected that a spin-glass (SG) transition, which generally occurs only in systems with some form of disorder, was observed in the ThCr2Si2-type compound PrAu2Si2at a temperature of ∼3 K. This puzzling phenomenon was later explained based on a novel dynamic frustration model that does not involve static disorder. We present the results of re-verification of the reported SG behaviors by measuring the physical properties of three polycrystalline PrAu2Si2samples annealed under different conditions. Indeed, in the sample annealed at 827 °C for one week, a SG transition does occur at a temperature ofTf∼ 2.8 K as that reported previously in the literature. However, it is newly found that the SG effect is actually more pronounced in the as-cast sample, and almost completely disappears in the well-annealed (at 850 °C for four weeks) sample. The annealing effect observed in PrAu2Si2, that is, SG to paramagnetism transition is discussed by comparing with earlier results reported on the same system and other isomorphic compounds.

A clinical investigation into the usefulness of fractional exhaled nitric oxide in guiding glucocorticoid therapy in children with bronchial asthma.

The present study aims to investigate the value of fractional exhaled nitric oxide (FeNO) combined with pulmonary function in guiding the dose adjustment of inhaled glucocorticosteroids (ICSs) in children with asthma. A total of 133 children aged 6-12 years with newly diagnosed asthma were enrolled as the study subjects and randomly divided into the experimental group (n=68) and the control group (n=65). After three months of ICS treatment, in the experimental group, the dose of ICSs was adjusted based on the control status of the children and the results of the pulmonary function tests and FeNO assays, and in the control group, the dose was adjusted based on the control status of the children and the results of the pulmonary function tests. After another three months of treatment, the number of acute asthma attacks and the Childhood Asthma Control Test (C-ACT) scores were compared between the two groups, and the outcome of pulmonary function tests and FeNO assays during treatment were analyzed. When examining pulmonary function and FeNO levels, when compared with before treatment, there were no statistically significant differences in either group or between the groups after three months of ICS treatment (P>0.05). After dose adjustment and another three months of treatment, when compared with the control group, the improvement in pulmonary function in the experimental group was greater, the reduction in FeNO levels was greater, the incidence of acute asthma attacks was lower, and the C-ACT score was higher (P<0.05). We concluded that the combination of FeNO assays and pulmonary function tests to guide the ICS dose adjustment in children with asthma could improve asthma control and reduce the risk of acute asthma attacks.

[Surveillance for sever fever with thrombocytopenia syndrome in Henan province, 2017-2020].

Objective: To analyze the epidemiological and etiological characteristics of sever fever with thrombocytopenia syndrome (SFTS) cases in Henan province during 2017-2020. Methods: Descriptive epidemiology method was used to analyze the characteristics of SFTS cases in Henan during 2017-2020. Patients' sera in acute phase were collected and tested using real-time fluorescence RT-PCR. The S segment complete sequences of the isolated sever fever with thrombocytopenia syndrome virus (SFTSV) strains were amplified and homology analysis was performed to construct the phylogenetic tree. Results: A total of 1 767 SFTS cases, including 1 000 suspected cases and 767 confirmed cases, were reported in Henan during this period, and 11 cases, including 3 suspected cases and 8 confirmed cases died, the case fatality rate was 0.62% (11/1 767). The incidence decreased year by year. The cases were distributed in 28 counties of 6 cities, and 1 681 cases were reported in Xinyang, accounting for 95.13% (1 681/1 767) of the total. The cases mainly occurred from April to October, accounting for 96.10% (1 698/1 767) of the total. The incidence in males (0.38/100 000) was significantly lower than that in females (0.54/100 000) (χ2=54.855, P<0.001). Up to 93.44% (1 651/1 767) of the cases were aged between 40 and 84 years. Farmers accounted for 96.10% (1 698/1 767) of the total cases. One family cluster outbreak occurred in 4 years. A total of 1 110 samples were detected by Henan CDC, in which 435 were SFTS virus positive with an average positive rate of 39.19% (435/1 110). The differences in positive rates of SFTS virus among different years were significant (χ2=25.405, P<0.001). The sequence homology of complete S segment of the 39 SFTS virus strains ranged from 94.76% to 99.82%. The genetic evolution analysis on the complete S segment of the 39 SFTS virus strains showed that 34 strains belonged to genotype A, 2 strains belonged to genotype B, and 3 strains belonged to genotype D. Conclusions: The incidence of SFTS in Henan was sporadic, and decreased year by year. SFTS had obvious regional and seasonal characteristics, and the area affected by SFTS expanded. The incidence of SFTS was high in elderly female farmers, and the positive rate of SFTS virus varied greatly in different years. The main type of SFTS virus in Henan was genotype A, but the etiological surveillance is still needed.

[Clinical and genetic studies on 76 patients with hydrocephalus caused by methylmalonic acidemia combined with homocysteinuria].

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 χ2 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.