OBJECTIVE: To explore the clinical and genetic characteristics of five children with Catecholaminergic polymorphic ventricular tachycardia (CPVT). METHODS: Five children with clinical manifestations consistent with CPVT admitted to the Department of Cardiology of Children's Hospital Affiliated to Zhengzhou University from November 2019 to November 2021 were selected as the study subjects. Their clinical data were collected. Potential variants were detected by whole exome sequencing, and Sanger sequencing was used to verify the candidate variants. All patients were treated with β-blocker propranolol and followed up. RESULTS: All patients had developed the disease during exercise and presented with syncope as the initial clinical manifestation. Electrocardiogram showed sinus bradycardia. The first onset age of the 5 patients were (10.4 ± 2.19) years, and the time of delayed diagnosis was (1.6 ± 2.19) years. All of the children were found to harbor de novo heterozygous missense variants of the RYR2 gene, including c.6916G>A (p.V2306I), c.527G>C (p.R176P), c.12271G>A (p.A4091T), c.506G>T (p.R169L) and c.6817G>A (p.G2273R). Among these, c.527G>C (p.R176P) and c.6817G>A (p.G2273R) were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.527G>C (p.R176P) was classified as a pathogenic variant (PS2+PM1+PM2_Supporting+PM5+PP3+PP4), and the c.6817G>A (p.G2273R) was classified as a likely pathogenic variant (PS2+PM2_Supporting+PP3+PP4). The symptoms of all children were significantly improved with the propranolol treatment, and none has developed syncope during the follow up. CONCLUSION Discovery of the c.527G>C (p.R176P) and c.6817G>A (p.G2273R) variants has expanded the mutational spectrum of the RYR2 gene. Genetic testing of CPVT patients can clarify the cause of the disease and provide a reference for their genetic counseling.
Child ; Humans ; Mutation ; Propranolol ; Ryanodine Receptor Calcium Release Channel/genetics* ; Syncope ; Tachycardia, Ventricular/diagnosis* ; United States

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.

Objective:To observe the clinical effects of hot-wet compression with Xiaohua ointment for acne mastitis in mass stage and its impacts on humoral immune function and inflammation.Methods:85 cases of patients with acne mastitis in mass stage treated in our hospital from January 2018 to January 2019 were selected as the research objects and randomly divided into control group (42 cases) and observation group (43 cases). The control group taken Tuoli xiaodu powder and external use of purple detumescence cream, and the observation group received hot-wet compression with Xiaohua ointment additionally. All treated for 30 days. The clinical efficacy, symptom scores, breast mass size, humoral immune indexes, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were compared, and the adverse reactions were recorded.Results:After treatment, the humoral immune indexes of the two groups had no significant change ( P>0.05), but the pain score, breast tumor size, mass score, CRP and ESR were significantly decreased than those before treatment ( P<0.05); compared with the control group, the pain score, breast tumor size and mass score in the observation group were significantly lower than those in the control group ( P<0.05). The total effective rate of the observation group was 83.7%, which was significantly higher than 59.5% of the control group ( P<0.05). There were no obvious adverse reactions in both groups. Conclusions:Hot-wet compression with Xiaohua ointment is effective and safe for patients with acne mastitis in mass stage, and could improve their inflammation.

Objective:To observe the compatibility of Xiaoaiping injection and insulin for injection in glucose infusion. Methods:The changes in appearance, particles and pH of the mixture in 24h at ambient temperature were observed. The concentration of chloro-genic acid and insulin were determined by HPLC. Results:There were no obvious changes in appearance, pH, precipitation or turbidi-ty generation, and the contents of insulin and chlorogenic acid kept stable in 12 h. The number of insoluble particles was stable in 12 h, and then gradually increased in 24 h. Conclusion:Xiaoaiping injection and insulin in 5％ glucose infusion is stable in 12h under the testing conditions.

Objective: To study the clinical characteristics, methods of diagnosis and treatment of hyperornithinemia-hyperammonemia- homocitrullinuria (HHH) syndrome. Method: From July 2011 to August 2016, 3 Chinese patients with HHH syndrome were enrolled in this study. The clinical course, biochemical features, brain MRI findings, and gene mutations were analyzed. Result: The three patients′ age at onset of symptoms was 3 months to 7 years, and the age of diagonosis was 3 years and 10 months to 9 years and 10 months. All of them presented with intolerance to protein-rich foods from the infant period, development retardation and abnormal posture. Case 1 and 2 had moderate mental retardation. Serum ammonia 25-276 μmol/L (reference range<60 μmol/L), alanine aminotransferase (ALT) 20-139 IU/L (reference range 9-50 IU/L), ornithine 29.12-99.44 μmol/L(reference range 15-100 μmol/L), urinary orotic acid 1.49-29.75 mmol/mol Cr (reference range 0-7 mmol/mol Cr), uracil 6.09-103.97 mmol/mol Cr (reference range 0-1.5 mmol/mol Cr). The cranial MRI revealed lesions in the basal ganglia, abnormal white matter signal, progressive demyelination and cerebral atrophy. On their SLC25A15 gene, a novel homozygous missense mutation c. 416A>G (p.E139G) was identified in case 1, a known pathogenic homozygous nonsense mutation c. 535C>T was found in case 2 and 3. Liver transplantation had been performed when case 1 was 6 years old. Significant improvements were observed in dietary habit, mental and motor functions, and biochemical parameters. After the dietary intervention with the supplements of arginine, L-carnitine, case 2 was improved, spastic paraplegia of case 3 had no mitigation. Liver transplant was recommended. Conclusion HHH syndrome has an aversion to protein-rich food, and the patients have recurrent vomiting and progressive neurological dysfunction. Clinical diagnosis of HHH syndrome is difficult and patients may present with incomplete biochemical phenotype. The genetic analysis is key for the diagnosis. Depending on their condition, individuals with HHH syndrome can be treated with a low-protein diet, drugs and liver transplantation.

Objective:To understand the mode and effect of the consultations involved clinical pharmacists, and discuss the work-ing process and mode of the consultations. Methods:Based on the practical work and team discussion, the flow chart and consultation registration form for the clinical pharmacist consultations were established and applied. Totally 410 cases of clinica1 pharmacist consul-tations were retrospectively investigated from March 2009 to December 2012. Results:The consultation flow chart was strictly followed by the clinical pharmacists in our hospital, and the obvious effect was shown. The number of consultation was increased from 59 cases in 2009 to 122 cases in 2013. In all the consultation cases, 21 departments were involved, including the medical departments and the surgery departments. Among the cases,the adjustment in antibacterial drug treatment was the main requirements. Meanwhile, the a-doption rate of the clinical pharmacist suggestions was 95. 12%. Conclusion:Clinical pharmacists are playing an important role in clin-ical treatment. The consultation work can be regulated by the consultation flow chart and registration form with the improved adoption rate and consultation quality.

Objective To explore value of trephine in pedicle subtraction osteotomy (PSO) for old thoracolumbar compression fracture with kyphotic deformity.Methods Thirty seven patients who underwent surgical treatment for old thoracolumbar kyphotic deformity in our hospital from February 2005 to February 2010 were retrospectively reviewed.Among them,21 patients underwent conventional PSO and 16 patients underwent PSO with trephine.In conventional PSO group,there were 14 males and 7 females,the average age was 55.6±3.7 years and the mean Cobb angle was 45.3°±4.6°.In PSO with trephine group,there were 11 males and 5 females,the average age was 53.3±4.2 years and the mean Cobb angle was 47.6°±5.9°.Results All patients were successfully followed up.The duration of follow-up ranged from 12 to 22 months in conventional PSO group,while 13 to 20 months in PSO with trephine group.The operation time,blood loss,amount of blood transfusion were 224±45 min,1043±234 ml,876±300 ml respectively in conventional PSO group,while 180±31 min,785±163 ml,500±230 ml in PSO with trephine group.Immediately after operation,correction rate of Cobb angle was 91.4％ in conventional PSO group and 90.9％ in PSO with trephine group.At final follow-up,the correction of Cobb angle lost 5.8％ in conventional PSO group and 6.2％ in PSO with trephine group.The improvement rate of JOA score was 81.1％ in conventional PSO group and 83.7％ in PSO with trephine group.The VAS score decreased 7.7±1.1 in conventional PSO group and 7.8±0.8 in PSO with trephine group.One patient in conventional PSO group experienced saddle numbness immediately after operation,which alleviated at final follow up.All patients achieved bony fusion at final follow up.No infection,screw loosening or breakage occurred in both groups.Conclusion The use of trephine in PSO for old thoracolumbar compression fracture with kyphotic deformity can reduce operation time,blood loss and improve efficiency of osteotomy.

Objective To investigate proteolipid protein 1 (PLP1) mutations in six pedigrees with Pelizaeus-Merzbacher disease (PMD),and to provide prenatal consulting and prenatal diagnosis.Methods Subjects were six probands with PMD admitted in Department of Pediatrics,Peking University First Hospital from July 2006 to November 2011 and their family members.Genomic DNA sarnples were extracted from peripheral bloods of probands and their family members.Multiplex ligation-dependent probe amplification (MLPA) technique was used to detect PLP1 duplication mutation.Direct DNA sequencing was used to detect point mutation.Genetic diagnosis were based on PLP1 mutation genotype from probands.Prenatal diagnosis of nine fetuses were performed from seven PLP1 mutation female carriers by fetuses' DNA extracted from amniocytes or villus cells.Results PLP1 duplications were found in probands 1-4 (P1-4) whose mothers and the aunt of proband 1 (P1) were PLP1 duplications carriers.The two cases of point mutation,c.96C＞G(p.F32L) and c.623G＞T (p.G208V),were found in proband 5 (P5) and proband 6 (P6).Hcterozygous changes of the same mutations were found in P5' and P6' mothers with normal phenotypes.Seven female PLP1 mutation carriers were pregnant again.Prenatal diagnosis of PLP1 for nine fetuses presented one PLP1 duplication,one point mutation,one PLP1 duplication carrier,and six wildtypes.A segmental crossing over of X chromosome was detected in one male fetus of PLP1 wildtype.Conclusions PLP1 mutation analysis could help to diagnose PMD pedigree and to identify female PLP1 mutation carrier in the family.The following prenatal diagnosis and proper genetic counseling are very important to prevent PMD child from being delivered.

Objective To investigate the effects of losartan on aortic elasticity and remodeling in spontaneously hypertensive rats (spontaneously hypertensive rats SHR). Methods WKY (Wistar - Kyoto ) rats with normal blood pressure and 16 weeks spontaneously hypertensive rats were randomly divided into WKY control group, SHR control group, high dose losartan group (SHR + HL), low doses losartan group (SHR + LL). Each group has six animals which were given normal diet for 24 weeks. Losartan which was dissolved in 10 ml physiological saline was filling in stomach, other groups were filling with physiological saline. Tail arterial blood pressure, kidney tissues calcium concentration, renal small artery hydroxyproline content was measured and small arteries wall thickness of Glomerularwas detected, and the ratio of thickness and inner diameter (MT/LR) in kidney pathological were observed. Results The calcium concentration of SHR group in kidney tissues was [(18.42±2.34)μmol/g], kidney small artery hydroxyproline content was [(8.26±2.02)mg/g], which were greater than WKY group [(11.83±1.98)μmol/g,(5.16±0.98)mg/g] (t＝3.116,3.258,P＜0.05), but the two treatment groups were less than SHR group (t＝2.946,P＜0.05), the difference was significant. Small arteries wall thickness of Glomerular was [(5.25±1.13)μm], the ratio of thickness and inner diameter (MT/LR) was [(9.57±1.78)%], which were greater than WKY group[(4.03±0.16)μm ,(7.12±1.35)%](t＝2.836,3.425,P＜0.05), but the wall thickness of two treatment groups were [(7.64±1.29)%,(7.85±1.32)%], the two treatment groups were less than SHR group (t＝3.512,3.648,P＜0.05). Conclusions Losartanmay inhibit intracellular calcium overload, reduce fibrosis degree and improve renal arteriole resistance and reverse the renal arteriole reconstruction of SHR rats.

Objective: To observe the characteristics of dynamic changes of lysophosphatidic acid (LPA) levels in cerebrospinal fluid (CSF) in patients with subarachnoid hemorrhage (SAH) and its relationship with cerebral vasospasm (CVS) and to explore the pathogenesis of CVS. Methods: Sixty-seven patients with SAH diagnozed by clinical and accessory examinations were selected. The LPA levels in CSF were measured at 24 hours, day 7,14, and 28 respectively after the onset of symptoms,and they were compared with a control group. The correlation between LPA levels and CVS on the time course was also observed at the same time. Results: Of the 67 patients with SAH, a total of 29 patients (43.3%) occurred CVS, the average time of occurrence was 6. 6 days. There was no significant difference between the LPA levels in CSF in patients with SAH and the control group at 24 hours after the onset of symptoms; they were significantly higher than the control group at day 7 (P ＜0. 001); they were significantly higher than the control group at day 14 (P ＜ 0. 001), but they were significantly lower than those at day 7 (P ＜ 0. 01); they decreased to baseline at day 28, and there was significant difference compared with the control group. There was no significant difference between the LPA levels in the CVS group and those in the non-CVS group at 24 hours, they were significantly higher than those in the non-CVS group at day 7 (P ＜0. 001), they were still significantly higher than those in the non-CVS group at day 14 (P ＜0. 01); and there was no significant difference between the 2 groups at day 28. Conclusions: The LPA levels in CSF in patients with SAH increased significantly from day 7 to day 14 after the onset of symptoms, and they had obvious association with CVS on the time course. The detection of the LPA levels in CSF may have important significance in predicting the occurrence of CVS.