BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an underdiagnosed genetic heart disease worldwide. The management and prognosis of obstructive HCM (HOCM) and non-obstructive HCM (HNCM) are quite different, but it also remains challenging to discriminate these two subtypes. HCM is characterized by dysmetabolism, and myocardial amino acid (AA) metabolism is robustly changed. The present study aimed to delineate plasma AA and derivatives profiles, and identify potential biomarkers for HCM. METHODS: Plasma samples from 166 participants, including 57 cases of HOCM, 52 cases of HNCM, and 57 normal controls (NCs), who first visited the International Cooperation Center for HCM, Xijing Hospital between December 2019 and September 2020, were collected and analyzed by high-performance liquid chromatography-mass spectrometry based on targeted AA metabolomics. Three separate classification algorithms, including random forest, support vector machine, and logistic regression, were applied for the identification of specific AA and derivatives compositions for HCM and the development of screening models to discriminate HCM from NC as well as HOCM from HNCM. RESULTS: The univariate analysis showed that the serine, glycine, proline, citrulline, glutamine, cystine, creatinine, cysteine, choline, and aminoadipic acid levels in the HCM group were significantly different from those in the NC group. Four AAs and derivatives (Panel A; proline, glycine, cysteine, and choline) were screened out by multiple feature selection algorithms for discriminating HCM patients from NCs. The receiver operating characteristic (ROC) analysis in Panel A yielded an area under the ROC curve (AUC) of 0.83 (0.75-0.91) in the training set and 0.79 (0.65-0.94) in the validation set. Moreover, among 10 AAs and derivatives (arginine, phenylalanine, tyrosine, proline, alanine, asparagine, creatine, tryptophan, ornithine, and choline) with statistical significance between HOCM and HNCM, 3 AAs (Panel B; arginine, proline, and ornithine) were selected to differentiate the two subgroups. The AUC values in the training and validation sets for Panel B were 0.83 (0.74-0.93) and 0.82 (0.66-0.98), respectively. CONCLUSIONS The plasma AA and derivatives profiles were distinct between the HCM and NC groups. Based on the differential profiles, the two established screening models have potential value in assisting HCM screening and identifying whether it is obstructive.
Humans ; Amino Acids ; Cysteine ; Cardiomyopathy, Hypertrophic/diagnosis* ; Biomarkers ; Proline ; Arginine ; Ornithine ; Glycine ; Choline

Objective: To explore the clinical effect of percutaneous low frequency electric stimulation on prevention of venous indwelling needle thrombotic blockage in patients with coronary heart disease. Methods: A total of 150 patients admitted to the department of cardiovascular medicine from May 2017 to January 2018 who met the inclusion and exclusion criteria were selected. It was divided into the intervention group and the control group by the random number table method, including 75 cases in the intervention group and 75 cases in the control group. In the control group, the routine nursing method was adopted for the maintenance of intravenous indwelling needle. In the intervention group, on the basis of routine nursing, the percutaneous low frequency electrical stimulation was added. The incidence of thrombosis, occlusion, mean retention time, patient satisfaction and intravenous infusion complications were compared between the two groups. Results: The incidence of thrombosis was 40.0% (30/75) and64.0% (48/75) in the intervention group and the control group, and the blockage rate was 28.0% (21/75) and 52.0% (39/75) in the intervention group and the control group, respectively. There were significant differences between the two groups (χ²=8.654, 9.000, all P< 0.01). The incidence of phlebitis, drug exosmosis and subcutaneous bruising were 13.33% (10/75), 13.33% (10/75) and 18.67% (14/75) in the intervention group, 33.33% (25/75), 40.00% (30/75) and 41.33% (31/75) in the control group, respectively. There were significant differences between the two groups (χ² = 8.385, 13.636, 9.175, all P< 0.01). The indwelling time and patient satisfaction of the intervention group were (2.817±0.221) d and 82.67% (62/75) respectively, while those of the control group were (2.291±0.127) d and 50.67% (38/75), respectively. There were significant differences between the two groups (t=17.926, χ²=17.280, all P<0.01). Conclusions Percutaneous low frequency electrical stimulation has positive significance for improving the formation of thrombus at the point of intravenous indwelling needle and preventing the blockage of catheter caused by thrombosis.

To investigate the effects of ventricular shunt placement in children with post-infective hydrocephalus.
 Methods: A total of 24 cases of post-infectious hydrocephalus, who received ventricular shunt, were enrolled. Age, gender, disease progression, clinical manifestation, laboratory data, treatment, prognosis, complication, and sequela for each patient were retrospectively reviewed.
 Results: Of the 24 cases, 8 had a full recovery, 11 had slight sequela, 2 had severe sequela, 1 was in vegetative state, and 2 died because of bacterial meningitis and tubercular meningitis. Epilepsy, mental impairment, visual and hearing damage were the main sequelae.
 Conclusion: Ventricular shunt is the preferred treatment in children with post-infective hydrocephalus, which shows positive clinical efficacy and can improve the long-term prognosis of such patients.
Child ; Humans ; Hydrocephalus ; Retrospective Studies ; Treatment Outcome ; Tuberculosis, Meningeal ; Ventriculoperitoneal Shunt

Objective: Victims with shock-able initial arrest rhythms (ventricular fibrillation or pulse-less ventricular tachycardia, VF/VT) have much better outcomes from out-of-hospital cardiac arrest (OHCA) than those with non-shock-able initial rhythms (pulse-less electrical activities, PEA or asystole). Prompt defibrillation is believed pivotal to terminate lethal shock-able arrest rhythms. In this study, we were to identify those pre-hospital epidemiological factors which were associated with likelihood of shock-able rhythms first recorded when out-of-hospital cardiac arrest occurred. Methods: A multicenter, secondary, retrospective and observational analysis was performed on all adult non-traumatic OHCA in the Resuscitation Outcome Consortium (ROC) PRIMED study from June 2007 through November 2009. Of a total of 17 177 OHCA cases in PRIMED study, 13 421 of them were enrolled in this study when those OHCA patients with DNR order, or initial rhythms unknown, or arrest caused by obvious cause were excluded. We reported their demographics and episode characteristics for all enrolled cases. Multivariable logistic regression was employed to identify factors which were associated with likelihood of VF/VT recorded as shock-able initial rhythms. Results: Among 13 421 adult non-traumatic OHCA cases with initial rhythms recorded, 3 527 (26.3%) of them had shock-able rhythms, while 9 894 (73.7%) patients were in non-shock-able rhythms. Of the OHCA with shock-able arrest rhythms, 1 850(52.5%) obtained return of spontaneous circulation (ROSC) in the field, while 912 (25.9%) survived to hospital discharge. On the other hand, 2489(25.2%) of the OHCA with non-shock-able arrest rhythms obtained ROSC in the field, while 325 (3.3%) of them survived to hospital discharge. Multivariable regression analysis revealed those factors which indicated likelihood of shock-able rhythms recorded were: age(OR: 0.991,95%CI 0.988-0.993), male gender (OR1.887,95%CI1.718-2.073), pre-hospital Emergency Medical System(EMS) response time(OR0.950,95%CI 0.931-0.970), cardiac arrest witnessed by EMS providers(OR1.709,95%CI 1.423-2.054) or bystander(OR3.199,95%CI 2.921-3.504) and those with bystanders CPR (OR1.357,95%CI 1.239-1.487),public place of cardiac arrest (OR2.705,95%CI 2.437-3.003). Conclusions Some demographics and pre-hospital characteristics were proved associated with likelihood of shock-able arrest rhythms first recorded in OHCA victims, which might help develop corresponding strategies to deliver prompt shock on initially shock-able patients and improve their outcomes.

Objective: To report a family diagnosed with Allan-Herndon-Dudley syndrome (AHDS) due to SLC16A2 gene mutation and to summarize the phenotypes, genotypes, diagnosis, treatment, and prognosis. Methods: The clinical features of a family of AHDS diagnosed in Xiangya Hospital of Central South University in November 2017 were analyzed. Related literature was searched at Online Mendelian Inheritance in Man (OMIM), PubMed, CNKI and Wanfang database (from the establishment of databases to June 2018) by using "Allan-Herndon-Dudley syndrome" , and "AHDS" as keywords and the case reports from April 2013 to June 2018 were reviewed. Results: The proband was a boy aged 8 months who presented with global developmental retardation, inability to hold up the head, disability to sit independently or grab, no language development, elongated face, big ears, esotropia, scoliosis, hypotonia in the trunk, hypertonia in extremities, and hyperreflexia. Brain magnetic resonance imaging (MRI) showed widening of the extracerebral space and delayed myelination. Thyroid function tests revealed increased FT3, decreased FT4 and normal TSH. Whole exome sequencing (WES) revealed the SLC16A2 gene c.431-1 (IVS1) G>C hemizygous mutation. The infant's mother and grandmother are carriers, but whose father had no related mutation. One uncle from maternal side had severe psychomotor retardation as well as dystonia and died at one year of age with unknown etiology. A total of 97 articles were retrieved in which 19 case reports were reviewed. Forty-two cases (22 from 8 families and 20 sporadic) were reported. Among these 42 cases (all males), all of them presented with moderate to severe cognitive dysfunction, 15 with seizures; 36 were bedridden, only 4 could walk; 31 had no language development, 2 could speak sentences, 4 could speak few words, 1 had babbling sounds. Furthermore,16 had microcephaly, 18 had facial dysmorphism, 6 had esotropia, 2 had hearing loss,14 had scoliosis, 11 had joint contracture, 30 had low body weight/muscle wasting, 37 had hypotonia in trunk or extremities, 32 had progressive spastic paraplegia or hypertonia. In terms of thyroid function, 33 had abnormal results, within whom 30 had increased T3, 25 had decreased T4 and 3 had increased TSH. Brain MRI showed delayed myelination in 22 cases, within which one normalized with development. Genetic tests showed that 31 had missense mutation (14 sporadic), 5 had deletion mutation (3 sporadic, and 1 due to frameshift mutation), 5 had insertion mutation (2 sporadic), and 1 had repeated mutation. The prognosis was poor as patients often died of recurrent respiratory tract infection. Conclusions The main clinical manifestations of AHDS are severe global developmental retardation, hypotonia, spastic paraplegia, abnormal serum levels of thyroid hormone and delayed brain myelination. SLC16A2 c. 431-1 (IVS1) G > C mutation is accountable for this disease.

Background and purpose:The effective rate of ifrst-line chemotherapy for advanced lung cancer is 30%-40%. The purpose of this study was to evaluate the efifcacy and adverse effects of pemetrexed combined with carboplatin or cisplatin in the treatment of patients with advanced non-squamous non-small cell lung cancer (NSCLC). Methods:One hundrend and twenty-one patients with advanced non-squamous NSCLC were enrolled in this study and all of these patients had been conifrmed with pathology or cytology. Among the 121 cases, 60 cases were male and 61 were female, the median age was 59 years, adnenocarcinoma in 113 patients and large cell carcinoma in 8 patients. Combination regimen: patients received pemetrexed 500 mg/m2 on day 1 and carboplatin 300 mg/m2 or cisplatin 70 mg/m2 on day 1 by intravenous infusion, administrated every 3 weeks for 2 to 6 cycles. All patients who received 2 or more cycles could be evaluated. Disease control rate (DCR) was the primary end point; secondary end points included progression-free survival (PFS), 1-year survival rate and safety.Results:There was 1 case with complete response (CR), 44 cases achieved partial response (PR), 50 had stable disease (SD) and 26 cases had progressive disease (PD) in the overall cases. ORR and DCR were 37.2% (45/121) and 78.5% (95/121), respectively. The median PFS time was 5.2 months and 1-year survival rate was 59.0%. In pemetrexed combined with carboplatin group, the ORR and DCRwere 38.3% (23/60) and 78.3% (47/60), respectively; The median PFS was 5.1 months (95%CI: 3.8-6.4 month) and 1-year survival rate was 55.2%. The patients treated with pemetrexed plus cisplatin, the ORR and DCR were 36.1% (22/61) and 78.7% (48/61), respectively. Median PFS was 6.2 months (95%CI: 4.3-8.1 month) and 1-year survival rate was 62.5%. There were no statistical differences between carboplatin/pemetrexed and cisplatin/pemetrexed for both ORR, DCR, PFS and 1-year survival rate (P>0.05). The major adverse effects were leukopenia, neutropenia, fatigue and gastrointestinal reaction.Conclusion:Pemetrexed plus platinum chemotherapy could be considered as the ifrst-line treatment option for advanced non-squamous NSCLC patients. Pemetrexed combined with carboplatin/ cisplatin regimen has efifcacy with mild toxicity and better tolerability.

Background and objective hTe aim of this study is to establish a HRM (high resolution melting curve) method for detection of deletion in human BIM gene and to detect this site deletion with the above method in 30 lung cancer samples and 30 normal samples. Methods The primers for detection of BIM deletion were designed and synthesized. The HRM method for geng deletion was established. And select the part of samples to detect BIM delection by normal PCR and sequencing assay. hTe Tm value of wild type PCR products was higher than that of the deletion PCR products. hTe difference of the corresponding Tm value is 2.5 oC. Results By detection with HRM methods, 1 samples were conifrmed to be mutant, 7 samples were conifrmed to be heterozygous and the other 22 samples were all wild type in the lung cancer samples. 2 samples were conifrmed to be heterozygous and the other 28 samples were all wild type in the normal samples. Conclusion hTe HRM method for detection of BIM deletion established in this study is a sensitive, accurate, simple and high throughput method.

Objective To analyze the VP1 and VP4 genetic region of enterovirus 71 (EV71)isolated from severe cases and mild cases with hanD-foot-mouth disease (HFMD) in Shanghai in 2011.Methods Five EV71 strains isolated from severe cases and five EV71 strains from mild cases in 2011 were included.Reverse transcription-polymerase chain reaction (RT-PCR) method was used to amplify and sequence the VP1 and VP4 genes of EV71,and then the sequencing results were compared with those of A,B,C genotype reference EV71 strains from GenBank by nucleotide alignment,amino acid alignment and phylogenetic tree analyses.Results The homogeneity between EV71 strains from severe cases and mild cases was 96.0％-98.1％ and 93.7％-99.5％ for VP1 and VP4 nucleotide sequences,respectively.The VP1 nucleotide sequences of 5 strains isolated from severe cases and 5 strains from mild cases in Shanghai shared 86.9％-98.2％ and 87.4％ 98.5％ identity with genotype C,respectively,while the homogeneity of VP4 nucleotide sequence was 85.5％-100.0％and 84.5％-99.5％,respectively.In addition,compared with the Fuyang EV71 strains (representative of C4 subtype),the strains from mild and severe cases shared homogeneity of 97.0％-98.2％ and 97.9％-98.5％ for VP1 gene,respectively,96.1％-100.0％ and 97.1％-99.5％ for VP4 gene,respectively.Among 3 strains isolated from severe cases,mutations at the residue 282 in the VP1 protein (N→S) and residue 7 in the VP4 protein (T→A) were discovered simultaneously.Conclusions The 10 EV71 strains isolated from severe and mild cases in Shanghai belong to subgenogroup C4.Among 3 strains isolated from severe cases,mutations at the residue 282 in the VP1 protein (N→S) and residue 7 in the VP4 protein(T→A) are discovered simultaneously.

Objective To understand the genetic and antigenic variations of influenza A (H1N1) isolates in Shanghai area in winter of 2010.Methods A total of 137 throat swabs were collected from patients with influenza-like illness in the sentinel hospital in Shanghai area from December 2010 to January 2011,then inoculated into Madin-Darby canine kidney (MDCK) cells.The types of influenza were identified by direct immunofluorescence assay (DIF) and influenza A (H1N1) subtype was determined by reverse transcriptase-polymerase chain reaction (RT-PCR).The mutations of gene and amino acid locus were analyzed through the whole genome sequencing of hemagglutinin (HA),neuraminidase (NA) and polymerase (PB2) segments from some influenza A (H1N1) isolates.Results Total of 53 human influenza virus strains were isolated including 48 influenza A (H1N1) virus strains.Nineteen strains were selected for sequencing by simple random sampling.The phylogenetic tree of HA gene revealed that the latest isolates and most of influenza A (H1N1) viruses isolated before June 2010 were not in the same stem.Analysis of amino acid residues in HA protein showed that mutations were found in antigenic determinant region in some strains.Residues at the enzyme active sites of NA protein were strictly conservative,no change was observed in amino acid residues which were related to drug resistance against oseltamivir and zanamivir.The 627 and 701 residues in PB2 protein were glutamic acid and aspartic acid,respectively,which was still the feature of avian influenza virus,but E677G mutation was detected.Conclusion Compared to influenza A (H1N1) strains isolated in spring and summer,some variations have been detected in the strains isolated in Shanghai area in winter of 2010,some antigen drift and adaptive evolution in mammalian hosts have appeared.

Objective To evaluate shell vials of MHV,a combination of Madin-Darby canine kidney cells (MDCK),human epidermoid cancer cells (Hep-2) and African green monkey kidney cells (Vero),and conventional cell culture in detecting influenza viruses and enterovirus from fresh clinical specimens.Methods Specimens from patients with influenza-like illness and children with hand-foot-mouth disease were inoculated with both shell vials of MHV and MDCK/Vero.Then cytopathological effect (CPE) was examined daily.Influenza viruses and enteroviruses were detected by multiple reverse transcriptase-polymerase chain reaction (mRT-PCR).Results CPE of MDCK/Vero cells were stronger than the shell vials of MHV.The isolation rate of influenza virus by MHV was 24.6％ (34/138) and that by MDCK was 28.3％ (39/138),which was not significantly different (x2 =1.92,P＞0.05).That of enterovirus by MHV was 28.1％ (9/32) and that by Vero was 37.5％ (12/32),which was not significantly different (x2 =3.00.P＞0.05).Conclusions CPE in MDCK/Vero cells are easier to be observed than the shell vials of MHV.However,the shell vials of MHV are appropriate in public health emergencies,which can be used for isolation of influenza viruses and enterovirus in patients with respiratory symptoms.