Objective:To summarize the clinical and genetic characteristics of early-onset spinocerebellar ataxia type 5 (SCA5) caused by SPTBN2 gene mutation. Methods:The clinical and genetic data of a child with early-onset SCA5 diagnosed in the Department of Children′s Rehabilitation, Women and Children′s Hospital Affiliated to Qingdao University in February 2022 were retrospectively analyzed. The literatures related to early-onset SCA5 in major databases at home and abroad were retrieved and summarized.Results:The patient, a 4 years and 1 month old girl, was admitted to hospital because of "unable to stand independently at 2 years and 3 months", primarily presented with developmental delay, ataxia, hypotonia, and tendon hyperreflexia during infancy. Progressive cerebellar atrophy was observed on brain magnetic resonance imaging. A de novo heterozygous mutation of the SPTBN2 c.793G>C(p.Asp265His) was identified in the patient. Following hospitalization, the child received comprehensive rehabilitation therapy encompassing physical, occupational, language, educational interventions as well as bicycle ergometer training and transcranial magnetic stimulation. The patient was followed-up for more than 1 year to 4 years and 1 month old, whose motor function, cognitive abilities, and language skills were improved to some extent. A total of 13 English articles and 1 Chinese article were retrieved from the databases. A total of 20 early-onset SCA5 patients have been reported, with onset ages all within 12 months. Infants exhibited decreased muscle tone and delayed motor milestones, with the main clinical manifestations of ataxia, generalized developmental delay, and cerebellar atrophy. The previously reported cases involved 11 mutation sites in the SPTBN2 gene, and the main types of mutations were de novo missense mutations. The mutation site in this case has not been reported in the previous literature. Conclusions:Early-onset SCA5 is a rare autosomal dominant disorder caused by heterozygous mutations in the SPTBN2 gene. The main clinical manifestations include ataxia from infancy, developmental retardation and cerebellar atrophy. Early rehabilitation intervention can improve the degree of the dysfunction.

Objective:To investigate the molecular etiology of Perrault syndrome by analyzing the clinical phenotype and pathogenic gene variants of 2 male patients with bilateral severe sensorineural deafness.Methods:Two male patients with Perrault syndrome characterized by severe sensonrineual deafness adimitted to the First Affiliated Hospital of Zhengzhou University between February 2021 and March 2022 were selected, and the clinical phenotype and pathogenic gene variants of them and their family members were summarized. The whole exome sequencing technology was used to screen the pathogenic variants of the probands, and the candidate variants were determined by combining with clinical phenotype. The probands and their family members were verified by the Sanger sequencing method.Results:The whole exome sequencing results showed that the proband of family 1 had a compound heterozygous variants of the LARS2 (NM_015340.4) gene c.1565C>A (p.Thr522Asn) and c.1079T>C (p.Ile360Thr). The reported pathogenic variant c.1565C>A came from the mother, and the novel variant c.1079T>C came from the father. The second proband harbored compound heterozygous variants of HARS2 gene (NM_012208.4) c.1273C>T (p.Arg425Trp) and c.1403G>C (p.Gly468Ala), with the former from the proband′s mother, the latter from the father. The c.1273C>T was novel and c.1403G>C was the reported pathogenic variant. All above variants were respectively classified as pathogenic, uncertain significance, uncertain significance and likely pathogenic based on the ACMG guidelines. Conclusion:This study expands the mutational spectrum of LARS2 and HARS2 genes, which highlights that genetic testing plays an important role in the early diagnosis of syndromic deafness.

Objective:To screen the causative genes of five families with branchio-oto-renal syndrome (BORS) or branchio-oto syndrome(BOS) and to analyze the phenotypic characteristics and clinical management strategies of patients.Methods:Five families with BORS/BOR from December 2018 to September 2021 were recruited, information of patients, including family history and medical history, was collected, and genealogies were drawn. The examinations concerning audiology, nephrology, and radiology were performed on the affected individuals. Peripheral blood was obtained for DNA extraction, then next-generation sequencing technology was used to screen candidate variants associated with BORS/BOS. Based on patient′s clinical results, the appropriate interventions were recommended and implemented.Results:Eight individuals were diagnosed with BOS or BORS. Of the eight patients, all had hearing loss, preauricular pits and ear malformations, and only four presented with branchial cleft fistulae or cysts. Except for two patients(5-I-2, 5-II-2) who did not undergo renal examination, the remaining six lacked renal abnormalities. Genetic analysis identified four likely pathogenic or pathogenic EYA1 variants (c.1715G>T, c.1140+1G>A, c.639G>C, c.1475+1G>C; NM_000503.6), and c.1715G>T was first reported in this study. Middle ear ossicular reconstruction was performed in 1-II-2,2-I-2 and 3-II-2, but did not yield the expected results; then hearing aids and cochlear implantation were recommended and achieved satisfactory results. Conclusions:Next-generation sequencing technology facilitates the diagnosis and genetic counseling of BORS/BOS. Hearing loss, preauricular pits, ear malformations and branchial cleft fistulae or cysts are the most common manifestations of patients in this study. Middle ear surgeries for improving hearing loss may have some limitations in BORS/BOS patients, and hearing aids and cochlear implantation can contribute to hearing gains.

Objective To analyze the correlation between intestinal flora changes and neonatal necrotizing enterocolitis (NEC)through 16S rRNA metagenomic sequencing and bacterial culture. Methods From September 2018 to March 2019, 10 NEC cases and 6 controls were randomly selected in the neonatal ICU ward of Nanjing maternal and child health care hospital to analyze the 16S rRNA metagenomic diversity of the for intestinal flora. The fecal samples and corresponding environmental samples were corrected from 51 cases of NEC children and their case controls to isolate and culture Clostridium. Results The dispersion of samples within the case group was smaller than that of the control group, and the sample diversity was higher than that of the control group. In the isolation and culture of Clostridium, the overall detection rate of Clostridium in the case group was 43.14% (22/51), and the detection rate of Clostridium butyricum was the highest (19.61%, 10/51). There was a statistical difference between the two groups (χ²=5.85, P=0.015 58). All Clostridium strains did not carry the A, B and E type neurotoxin genes. Conclusion: Increased intestinal flora diversity, intestinal flora abundance and changes in the abundance of Clostridium may be closely related to the intestinal environment of children with NEC; Clostridium, especially Clostridium butyricum, may be related to the occurrence of NEC.

OBJECTIVETo explore the impact of electroacupuncture (EA) on the protein expression of adenosine receptors in the heart of the rats with myocardial ischemia (MI).

METHODSThirty healthy male SD rats were divided randomly into a control group (=6), a model group (=12) and an EA group (=12). We ligated the left anterior descending artery (LAD) for MI model in the model group and EA group, and exposed the heart after opening the chest without ligation in the control group. EA, 2 Hz /15 Hz and 1.5-2 mA, was applied at bilateral"Neiguan"(PC 6) in the EA group for 20 min, once a day for continuous 5 days. No intervention except grabbing and fixation was used in the control group and model group. We applied 2% TTC staining to observe the infarct size of myocardium, colorimetry to analyze serum lactic dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme (CK-MB), radio-immunity assessment to detect cardiac troponin T (cTnT), Western blot to evaluate the adenosine A1 receptor (A1AR), A2aAR, A2bAR and A3AR.

RESULTSAfter treatment, myocardial infarction of (27.56±3.24)% was obvious in the model group; the myocardial infarction in the EA group was (21.04±3.61)%, with statistical significance (<0.05). The expressions of serum LDH, CK, CK-MB and cTnT levels in the model group increased compared with those in the control group (all<0.01), and the expressions of LDH, CK, CK-MB and cTnT levels in the EA group decreased compared with those in the model group (<0.05，<0.01). The A1AR expression in the model group was not different from that in the control group (>0.05), and A2aAR、A2bAR、A3AR expressions decreased (<0.05,<0.01). A2aAR and A2bAR expressions in the EA group increased compared with those in the model group (both<0.01), and there was no statistical significance between A1AR and A3AR expressions (both>0.05). .

CONCLUSIONEA may achieve cardioprotective effect by regulating the expressions of A2aAR and A2bAR in myocardial tissue, which induce the corresponding signal cascade for reducing myocardial infarction area.

Objective To apply Nutritional Risk Screening-2002(NRS-2002) to perform primary screening for nutritional risk in patients with esophageal cancer who undergo radiotherapy, and assess their nutritional status, and to investigate the value of NRS-2002 in such patients.Methods A total of 97 patients who were diagnosed with esophageal cancer and underwent radiotherapy in Zhejiang Cancer Hospital from January 2010 to April 2014 were analyzed retrospectively.The Kaplan-Meier method was applied to analyze the difference in survival, and the chi-square test and the Pearson correlation analysis were applied to analyze the correlation between NRS-2002 score and blood parameters.Results Of all patients, 26.8%had nutritional risk before radiotherapy, which gradually increased with the progress of radiotherapy.The 1-year overall survival rates of the patients with NRS-2002scores of ≤3 and ≥4 on admission were 91.1%and 61.9%, respectively (P=0.010).As for the patients with the highest NRS-2002 scores of ≤2 and ≥3 during treatment, the 1-year overall survival rates were 94.2% and 77.5%, respectively (P=0.012).As for the patients with the lowest NRS-2002 scores of ≤3 and ≥4 during treatment, the 1-year overall survival rates were 91.3% and 54.5%, respectively ( P=0.018).The NRS-2002 score was correlated with prealbumin on admission and at week 1 of radiotherapy (P=0.000 and 0.002), and the NRS-2002 score was correlated with albumin at week 3 of radiotherapy (P=0.036).The multivariate analysis showed that the TNM stage of esophageal cancer and the highest NRS-2002 score during treatment were the independent prognostic factors in esophageal cancer (P=0.001 and 0.005).Conclusions The patients with esophageal cancer undergoing radiotherapy have high nutritional risk, and NRS-2002 score is the independent prognostic factor in these patients and can be used as a tool for primary screening for nutritional risk.

OBJECTIVETo conduct health economic evaluation of the prevention of mother-to-child HIV among pregnant women in Dehong prefecture, Yunnan province, China from 2004 to 2013.

METHODSData on cost were collected mainly from the annual prevention of mother-to-child transmission (PMTCT) reporting system of Dehong prefecture, and supplemented by HIV PMTCT-related resource allocation data from local health bureau. Effectiveness indexes were from local continuous HIV surveillance system and annual reported data. Cost-effectiveness and cost-utility analysis were used to conduct the health economic evaluation.

RESULTSFrom 2004 to 2013, 283980 pregnant women were screened for HIV, 2 059 were detected as positive, and the HIV positive rate was 0.73%. The total cost of the PMTCT program was 14 227 000 RMB after discounting, and the unit cost of positive case finding was 4 200 RMB. A total of 26 cases of adults and 325 infants were avoided HIV infection, and the cost-effectiveness ratio (CER) was 40 500 RMB/case. The total obtained quality adjusted life years (QALY) from the program was 8 911.5, each one of which cost 1 600 RMB/QALY. If the feeding pattern were breast feeding, CER would be 42 800 RMB/case and each one of QALY would cost 2 200 RMB.

CONCLUSIONBased on the cost-effectiveness and cost-utility analysis, the HIV PMTCT of Dehong prefecture had economic value, which indicates that continued investment is needed to strengthen local HIV PMTCT work.

Acquired Immunodeficiency Syndrome ; Adult ; Child ; China ; Cost-Benefit Analysis ; Costs and Cost Analysis ; Female ; HIV Infections ; Health ; Humans ; Infant ; Infectious Disease Transmission, Vertical ; Mothers ; Pregnancy ; Quality-Adjusted Life Years

Objective The study was to explore the effect of the Wechat combined with discharge supervision on rehabilitation of empty-nesters with total knee arthroplasty (TKA).Methods 100 emptynesters who were treated with unilateral TKA from September 2013 to August 2014 were selected and randomly divided into the experimental group and the control group with 50 patients in each group.All patients received the same orthopaedic hospital routine therapy and nursing,hospital rehabilitation exercise,guidance,family visits and conventional outpatient care.Besides the above treatment,the experimental group received nursing instruction after discharge by professional nurses through Wechat platform,which included functional exercise guidance,psychological guidance and daily activities instructions.The hospital for special surgery(HSS) knee score and the modified Barthel Index (MBI) score were assessed on the 14th day,the third month and the sixth month after surgery.Results HSS knee score and MBI score had no statistically significant difference between the experimental group and the control group on the 14 th day after surgery; HSS knee score and MBI score of the experimental group on the third month and the sixth month after surgery were significantly higher than those of the con-trol grou,t value was 9.24,11.07 and 21.92,14.14.Conclusions Wechat combined with discharge super-vision can effectively improve the rehabilitation effect of empty-nesters after total knee arthroplasty.

Objective:This study aims to determine the efficacy of chemotherapy and to identify potential chemotherapy agents for advanced primary duodenal carcinoma (PDC). Methods:Fifty-six patients with advanced PDC, who did and did not receive chemo-therapy, were involved in this study. Response rates (RR), disease control rates (DCR), progression-free survival (PFS), and overall sur-vival (OS) were analyzed. Results:The overall RR and DCR of 43 patients were 19.04%and 71.42%, respectively. The patients who re-ceived chemotherapy agents fluorourzcil and oxaliplatin exhibited higher RR compared with patients who received other chemotherapy combinations (35.29%vs. 7.69%, P=0.010 9). Palliative chemotherapy improved the OS of patients with advanced PDC compared with patients who did not receive chemotherapy (13.35 months vs. 5.65 months, HR=0.203, 95%CI:0.083 to 0.497, P=0.000 5). Compared with the use of other chemotherapy regimens, treatment with a fluorourzcil-based chemotherapy agent resulted in a longer PFS (5.08 months vs. 1.08 months, HR=0.004, 95%CI:0.000 to 0.315, P=0.013 2). Multivariate analysis indicated mucinous histology and lymph mode metastasis as factors predictive of poor prognosis in patients with advanced PDC. Conclusion:Palliative chemotherapy may im-prove the OS of patients with advanced PDC.

Objective:This retrospective study aims to determine the efficacy of chemotherapy and improve a salvage chemother-apy agent for metastatic colorectal cancer (MCRC) after failure of treatment with irinotecan and oxaliplatin. Methods:Between Janu-ary 2002 and March 2013, 37 patients with metastatic MCRC who had progressed after treatment with irinotecan and oxaliplatin were analyzed for their response rate (RR) and progression-free survival (PFS). Results:The overall RR of the 37 patients was 13.51%, with 5 cases of partial response (PR), 12 cases of disease stabilization (SD), and 20 cases of progression (PD). Compared with other chemo-therapy regimens, treatment with a pemetrexed-based chemotherapy agent had a higher RR (17.64%vs. 10.00%, P=0.64) without a lon-ger PFS (2.00 months vs. 1.63 months, HR=0.79, 95%, CI:0.35 to 1.78, P=0.58). Compared with other chemotherapy regimens, treat-ment with a raltirexed-based chemotherapy agent had a higher RR (16.67%vs. 12.00%, P=0.34) without a longer PFS (1.58 months vs. 1.90 months, HR=2.24, 95%, CI:0.98 to 5.12, P=0.06).Conclusion:In patients with MCRC after failure of treatment with irinotecan and oxaliplatin, a pemetrexed-based or raltirexed-based chemotherapy agent may beneficial during salvage treatment and is therefore worthy of further study.