Objective To summmrize the clinical characteristics complications,antimicrobial resistance and prognosis in 15 children with streptococcus pneumoniae meningitis so as to improve the diagnosis and treatment of this disease.Methods A systematic retrospective analysis was carried out in the Qilu Children's Hospital of Shandong University from Jan.2010 to Jan.2013,and clinical data from 15 children with streptococcus pneumococcal meningitis were retrospectively analyzed and followed up for 6 months in order to observe the prognosis.Results Eleven cases of streptococcus pneumoniae meningitis occuned in the winter and spring.And it often occuned in children less than 2 years of age who lived in rural areas (13 cases).The clinical manifestations showed diverse characteristics,severe symptoms,obvious changes in symptoms and cerebrospinal fluid were observed.Severe or death cases had low temperature,low leukopenia or low blood platelet.Common complications of streptococcus pneumoniae meningitis included anemia (10 cases),hypoalbuminemia (9 cases),sepsis (8 cases).Multi-drug resistance and complications in streptococcus pneumoniae meningitis led to the therapeutic difficulties.In this study,3 cases were cured,9 cases had varying degrees of sequences,such as left languages,sports,hydrocephalus and cognitive dysfunction,and 3 cases died,and the main cause of death was multiple organ dysfunction syndrome.Conclusions Streptococcus pneumoniae meningitis mainly occurred in the winter and spring.And the children under 2 years of age who lives in rural areas were often attacked.Clinical characteristics and cerebrospinal fluid changes obviously; severe cases are common with low temperature,low leukopenia or blood platelet.And there aye often diverse complications and multi-sequelae; the problem of multi-drug resistant and complications can lead to great difficulties in the clinical treatment.

Objective To investigate the clinical efficacy of prucalopride in the treatment of severe chronic constipation.Methods The clinical data of 60 patients with severe chronic constipation [slow transit constipation (STC), functional defecation disorder (FDD) and constipation-predominant irritable bowel syndrome (IBS-C)] who were admitted to the Third Affiliated Hospital of Nanjing University of Chinese Medicine from February to August 2014 were prospectively analyzed.A prospective, clinical observational study was performed.Treatment plans included that patients withdrew the initial treatments of laxative and exema and took orally 2 mg prucalopride once daily for 2 weeks, and continued to be treated by oral prucalopride if frequency of the spontaneous complete bowel movement (SCBM) per week was satisfactory (or improvement of symptoms was more than 50％) till 4 weeks, and then were followed up after stopping prucalopride.If improvement of symptoms was less than 50％ after 2-week treatment, other treatment plans were performed according to symptoms of patients from week 3 to week 6 : (1) for patients with STC, prucalopride + two chain bacillus subtilis probiotic capsules were administered orally if patients were satisfied with frequency of SCBM per week and without improvement of abdominal distension;prucalopride + Chinese herb decoction were administered orally if patients had improvement of frequency of SCBM per week with abdominal distension or poor stool output;oral prucalopride + acupuncture were administered if patients were unsatisfied with frequency of SCBM per week or less bowel movements and without improvement of abdominal distension or poor stool output.(2) For patients with FDD, oral prucalopride + acupuncture + biofeed-back therapy were administered.(3) For patients with IBS-C, prucalopride + two chain bacillus subtilis probiotic capsules were administered orally if patients had abdominal distension;prucalopride Chinese herb decoction were administered orally if patients had improvement of frequency of SCBM per week and no improvement of abdominal distension or poor stool output.All patients used a diary for recording the frequency of SCBM per week, stool consistence, exertion in defecation and adverse reactions, which was submitted to doctors for inputting data at the return visit weekly.Results There was good overall medicine compliance in patients.Of 60 patients, 43 patients completed treatments (21 with STC, 11 with FDD and 11 with IBS-C).After 2-week treatment, there were 19 patients with satisfied therapeutic effects, 14 with improvement of constipation and 10 with poor therapeutic effects.After 4-week treatment, constipation in 17 patients was cured, constipation in 18 patients was improved,and constipation in 8 patients was not improved.Nineteen of 60 patients were complicated with adverse reactions within 1 week of the medication, including 6 patients dropping out of the trial due to medication withdrawal and others with improvement by symptomatic treatment or spontaneous remission.Conclusions Prucalopride is effective for the treatment of severe chronic constipation with a good toleration, and it can improve the overall satisfaction of patients combined with Chinese herb decoction and acupuncture.

Objective: To identify the disease-causing mutations in a pedigree with familial hypertrophic cardiomyopathy (HCM) from Yunnan province, and analyze the relationship between the genotype and the phenotype. Methods: The blood samples and the clinical data of the HCM family members were collected.The coding exons and their flanking intronic regions of 28 previously reported genes related to HCM were screened in the proband by high-throughput sequencing. The mutations in proband were confirmed and detected in all family members as well as in 159 healthy controls by Sanger sequencing.The relationship between the genotype and the phenotype was analyzed in this pedigree. Results: Two missense mutations of Arg1045His and Ala26Val in β myosin heavy chain gene(MYH7) were identified. Genetic screening showed that the mother and brother of the proband carried Arg1045His mutation.Both mutations were absent in other family members and in 159 healthy controls.Disease onset age was less than 50 years old in this pedigree, chest pain, exertional dyspnea and syncope were the major symptoms, and all accompanied by severe left ventricular hypertrophy and left ventricular outflow tract stenosis.The grandma of the proband suffered sudden cardiac death. The proband had the worst symptoms and the earliest disease onset in this pedigree. Conclusions We find a pedigree with familial HCM from Yunnan province carrying MYH7 Arg1045His and Ala26Val mutations. The study suggests that Arg1045His mutation in MYH7 gene caused HCM is malignant with early onset, severe ventricular hypertrophy and poor prognosis. Arg1045His and Ala26Val double-mutant might have dosage effects and aggravate the clinical phenotype of the patient.

Objective To assess the level and trend of community acquired respiratory distress syndrome (CARDS) toxin after the infection of Mycoplasma pneumonia(MP),and evaluate the clinical characteristics,the level of immunoglobulin E (IgE) and interleukin-4 (IL-4) so as to find the association among these factors.Methods According to whether the child had wheezing symptoms,all the 63 children were divided into wheezing group (26 ca-ses) and non-wheezing group (3 cases).The levels of CARDS toxin were respectively detected in the acute stage of MP infection,3 and 6 months later after MP infection in different groups,moreover,IgE and IL-4 levels were monitored at the same time.Results (1) The mean level of IgE were (384.96 ± 316.62) × 103 IU/L and (87.32 ± 66.32) × 103 IU/L in wheezing group and non-wheezing group,respectively,and there was statistically significant difference (P ＜ 0.05).(2) The load of CARDS toxin in wheezing group and non-wheezing group were (1.87 ± 0.62) Delta Rn and (1.15 ± 0.48) Delta Rn in the stage of acute infection,respectively,and there was statistically significant difference (P ＜ 0.05).Nevertheless,differences between 2 groups after 3 months and 6 months were not significant.(3) In the acute stage,the level of CARDS toxin in the severe cases were higher than the mild cases [(2.37 ± 0.37) Delta Rn vs (1.21 ± 0.45) Delta Rn],and there was statistically significant difference (P ＜ 0.05).(4) IL-4 showed significant difference in the acute stage and 3 months later after acute infection between 2 groups,however,there were no difference between 2 groups after 6 months later.(5)The load of CARDS toxin showed no significant difference between 2 groups at 3 months [(0.96 ± 0.35) vs.(0.99 ± 0.40) Delta Rn,P =0.757] and 6 months [(0.67 ± 0.20) vs.(0.69 ±0.32) Delta Rn,P =0.641] later after MP infection.(6)The children in wheezing group coughed for (24.89 ±7.04) days after acute infection and the last time for non-wheezing group was (16.46 ± 4.79) days,and there was statistically significant difference(P =0.000).Conclusions The load of CARDS toxin decreased after acute MP infection and it was still detectable six months after onset in the blood.The level of CARDS toxin was associated with the cough and wheezing symptom and the severity of disease.

Objective:To explore the risk factors and follow-up outcomes of pediatric heart transplantation(HT).Methods:Between January 2018 and June 2022, perioperative data are retrospectively reviewed for 41 pediatric HT recipients aged <18 years and donor-recipient weight data for infants aged under 3 years at Guangdong Provincial People's Hospital.Perioperative survivors are followed up until August 31, 2022 through out patient visits and telephone calls.Postoperative survivals are examined by Kaplan-Meier method and possible risk factors for perioperative survival identify with Logistic regression.Results:There are 22 boys and 19 girls with a median age of 120(58~138)months.After preoperative adjuvant therapy of extracorporeal membrane oxygenation(ECMO), 8 cases had a successful transition to HT and 2 children underwent ABO incompatible(ABOi)HT.Six children aged under 3 years had a donor-recipient weight ratio of 2.95.Among 17 children, there are one or more complications, including continuous renal replacement therapy(CRRT, 9 cases, 21.95%), tracheotomy (3 cases, 7.32%), delayed chest closure or redo of sternotomy(6 cases, 14.63%)and acute graft dysfunction(4 cases, 9.76%). Five children died during perioperative period.The possible risk factors for perioperative mortality include preoperative ECMO assistance[ HR: 32.00, 95% CI: (2.83~361.79), P<0.05], preoperative CRRT[ HR: 11.33, 95% CI: (1.15~111.69), P<0.05] and total bilirubin [ HR: 1.02, 95% CI: (1.002~1.040), P<0.05]. During follow-ups, one child died from Epstein-Barr virus (EBV)associated post-transplant lymphoproliferative disease; another case of EBV-associated hepatic leiomyoma underwent transcatheter arterial embolization.With an overall survival rate of 85.37%, the cumulative survival rate is 96.97% for children without preoperative ECMO assistance( P<0.05). Postoperative mortality rate spiked markedly in children with preoperative ECMO assistance ( P=0.0013). However, follow-up results of perioperatively survivors indicate that preoperative usage of ECMO will not affect follow-up survival( P=0.53). In ABOi group or infants aged under 3 years, no mortality occurres postoperatively or during follow-ups. Conclusions:In infant aged under 3 years, the strategies of ABOi HT and large-weight donor HT are both safe and effective and it has no effect upon perioperative and follow-up survivals.Preoperative ECMO assistance, total bilirubin and preoperative use of CRRT are risk factors for perioperative survival.

Objective To explore the correlation between main indicators of donor liver and early prognosis after liver transplantation.Methods The clinical data of 166 donors and recipients of post-mortem organ donation (DD) from June 2017 to June 2018 were retrospectively analyzed.The effects of donor age,sex,body mass index,serum sodium level,total bilirubin,prothrombin time and international standardized ratio on early allograft dysfunction (EAD) in liver transplant recipients were investigated.According to the culture results of donor liver preservation solution,the results were divided into positive group and negative group.Combined with the culture results of blood,sputum and drainage fluid after liver transplantation,the early infection rate of recipients in the two groups was observed.Results Univariate analysis showed that preoperative donor bilirubin total ＞17.1 mmol/L and donor cold ischemia time ＞8 h were risk factors for postoperative EAD in transplant recipients.Multivariate analysis showed that donor cold ischemia time ＞8 h was an independent risk factor for postoperative EAD in liver transplant recipients;the incidence of EAD in the group with cold ischemia time ＞8 h was significantly higher than that in the group with cold ischemia time ≤8 h (26.3％ vs.7.0％;P =0.003).The positive rate of postoperative sputum culture and drainage fluid culture in the donors with positive donor culture was 43.9％ and 48.8％,respectively,which was significantly higher than that in the negative group (10.7％ and 13.1％).The difference was statistically significant (P =0.000,P =0.000).The positive rate of postoperative blood culture in the positive group and the negative group was 12.2％ and 6.0％ with the difference being not statistically significant (P =0.161).Conclusion Cold ischemia time of the donor ＞8 h is an independent risk factor for EAD in recipients after liver transplantation.Shortening the cold ischemia time of donor liver can reduce the incidence of postoperative EAD in recipients.The culture results of preservation solution have a certain guiding effect on the postoperative anti-infective treatment of the recipients.

Objective To investigate the age-related changes of biomechanical properties for humerus, femur and tibia in male rats and their application values in age estimation. Methods According to different weeks of age, 90 healthy male SD rats were divided into 2, 4, 6, 8, 17, 26, 52, 78 and 104-week groups with 10 rats in eachgroup. After the rats were executed by excessive anesthesia, humerus, femur, and tibia were separated and the attached soft tissues were removed. The length of the above-mentioned bones and the diameter of the middle section (compression site) were measured with vernier caliper, and the three-point bending test was conducted with electronic universal material testing machine to detect the ultimate load and displacement under ultimate load. Results There were significant differences in the ultimate load of humerus, femur and tibia among male rats in different age groups (P<0. 05). With the increase of week age, the ultimate loads of the humerus, femur and tibia increased first and then decreased, and reached the peak value in 52-week age group, showing a strong positive correlation with week age before 52 weeks ( r = 0. 884,0. 933,0. 929, P<0. 05). There was no significant difference in humerus and tibia. The displacement of femur under ultimate load was weakly positively correlated with week age (R= 0. 406,P<0. 05). The age prediction accuracy for automatic linear modeling of ultimate load for humerus, femur, tibia and three above-mentioned bones in rats before 52-week age was 78. 2% , 86. 8% , 84. 1% and 88. 3% , respectively. There was a strong positive correlation between the length of humerus, femur and tibia and the ultimate load (R= 0. 904, 0. 897, 0. 814, P<0. 05). The diameters of humerus, femur and tibia were strongly positively correlated with the ultimate load (R = 0. 759, 0. 814 and 0. 745, P<0. 05). Conclusions The ultimate loads of humerus, femur and tibia in male rats increased first and then decreased with age, and were positively correlated with age before 52 weeks, which could be used for age inference. The highest accuracy of age estimation was ultimate loads of three bones, followed by femur. The length/ middle diameter of humerus, femur and tibia were strongly positively correlated with the ultimate load.

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.‍T260A, p.‍R422W, and p.‍R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‍‒‍49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‍‒‍17.9%, which was significantly higher than that (6.9%‍‒‍7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.
Humans ; Apoptosis Inducing Factor/metabolism* ; NAD/metabolism* ; Dimerization ; Apoptosis