Objective To investigate the effectiveness of deep brain stimulation (DBS) treating Parkinson's disease.Methods Forty cases of Parkinson's disease were selected from March 2014 to August 2015.The clinical symptoms of these patients were described and quantitatively analyzed with Unified Parkinson's Disease Rating Scale (UPDRS) before and after the procedure of DBS surgery.Results After deep brain stimulation surgery,the symptoms including muscle stiffness,static tremor,bradykinesia were improved,UPDRS scores were significantly lower and the demanding dosage of Parkinson disease drugs such as L-dopa/benserazide and L-dopa/carbidopa were also reduced.Conclusion Deep brain stimulation for Parkinson's disease is safe and effective.It can obviously control the symptoms,reduce the dosage of oral drugs,and improve the quality of life.

Objective To investigate the value of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) based on ISHIM sequence in the grading of astrocytic tumor.Methods We collected excised tumors confirmed by histological diagnosis from 42 patients including high-grade astrocytic tumors (10 WHO grade Ⅲ,18 WHO grade Ⅳ),and 14 low-grade astrocytic tumors (1 WHO grade Ⅰ and 13 WHO grade Ⅱ).All patients underwent conventional MR imaging,ISHIM IVIM-DWI,and contrast-enhanced MR imaging.Parameters of tumor parenchyma region,peripheral edema regions and the contralateral normal brain white matter sites were measured,and the statistical analysis was conducted.Results The D value in tumor parenchyma region was significantly lower,but the D* and f values were higher in high-grade astrocytic tumor when compared with lowgrade one and all had statistical significance;in tumor peripheral edema region,D value was lower in high-grade astrocytic tumor than that in low-grade one,and the difference had statistical significance but there was no significant difference in terms of the D* and f values.There was no significant difference of the D,D* and f values in contralateral normal brain white matter sites in both high-and low-grade astrocytic tumor.Conclusion The D,D* and f values measured by ISHIM IVIM-DWI are helpful to the judgment of tumor grade and it has greatapplication value in the differential diagnosis of high-and low-grade astrocytic tumor.

OBJECTIVETo detect potential mutation of EXT1 gene in a pedigree affected with multiple osteochondroma and explore its pathogenic mechanism.

METHODSThe coding regions and their flanking sequences of the EXT1/EXT2 genes were subjected to PCR amplification and Sanger sequencing. Suspected mutations were verified by excluding possible single nucleotide polymorphisms and bioinformatics analysis. Transcripts of the EXT1 gene in the proband were analyzed by TA clone-sequencing, with its abundance compared with that of healthy controls.

RESULTSDNA sequencing has identified in the proband a novel heterozygous point mutation (c.1164+1G to A) at the 5'splice sites of intron 3 of the EXT1 gene. The same mutation was not found in the healthy controls. Bioinformatics analysis indicated that the mutation is highly conserved and can lead to skipping of exon 3 or aberrant splicing. TA clone-sequencing indicated that the numbers of transcripts with skipping of exon 3 has significantly increased in the proband (< 0.05) compared with the controls.

CONCLUSIONThe c.1164+1G to A mutation has resulted in skipping of exon 3 in a proportion of EXT1 gene transcripts. As the result, the number of transcripts with tumor suppressing function is relatively reduced and has ultimately led to the tumors.

Adult ; Base Sequence ; Child ; Exostoses, Multiple Hereditary ; genetics ; Female ; Humans ; Male ; Molecular Sequence Data ; N-Acetylglucosaminyltransferases ; genetics ; Point Mutation ; RNA Splice Sites ; RNA Splicing

OBJECTIVE: To explore the genetic basis for a pedigree affected with hereditary multiple osteochondroma (HMO). METHODS: Peripheral blood samples were collected from the proband and members of his pedigree with informed consent. Following extraction of genomic DNA, all coding exons and flanking intronic sequences (-10 bp) of the EXT1 and EXT2 genes were subjected to targeted capture and next generation sequencing (NGS). Suspected variant was verified by Sanger sequencing. RESULTS: A heterozygous nonsense variant (c.1911C>A) was found in exon 10 of the EXT1 gene in the proband and his affected father but not in a healthy sister and normal controls. The variant was classified as a pathogenic based on the guidelines of the American College of Medical Genetics and Genomics (PVS1+PM2+PP1). Bioinformatic analysis predicted that the c.1911C>A variant may be disease-causing via nonsense-mediated mRNA decay and anomalous splicing. CONCLUSION The c.1911C>A variant probably underlay the disease in this pedigree. Discovery of this variant enriched the variant spectrum of HMO.
Codon, Nonsense ; Exons/genetics* ; Exostoses, Multiple Hereditary/genetics* ; Heterozygote ; Humans ; Pedigree

Objective:To assess the correlation between hyperuricaemia and normoalbuminuric diabetic kidney disease(NADKD) in elderly type 2 diabetic patients.Methods:This retrospective case-control study enrolled 910 patients with type 2 diabetes mellitus who were hospitalized in the Geriatric Department of Nanjing Drum Tower Hospital from 2015 to 2020. The patients were divided into NADKD group [urinary albumin/creatinine(UACR)<30 mg/g and estimated glomerular filtration rate(eGFR) <60 mL·min -1·(1.73 m 2) -1, n=169)], albuminuria DKD group [UACR ≥30 mg/g and eGFR <60 mL·min -1·(1.73 m 2) -1, n=234], and control group [UACR <30 mg/g and eGFR≥60 mL·min -1·(1.73 m 2) -1, n=507]. Medical history, physical examination, and laboratory tests were collected. Results:The proportion of women in the NADKD group was significantly higher than that in the albuminuric DKD group(50.89% vs 40.60%, P<0.05). Duration of diabetes, HbA 1C, fasting plasma glucose(FPG), the prevalences of hypertension and hyperuricaemia, blood urea nitrogen, blood creatinine, and blood uric acid were significantly lower in the NADKD group than those in the albuminuric DKD group(all P<0.05). Blood urea nitrogen, serum creatinine, triglycerides, serum uric acid and the prevalence of hyperuricemia were significantly higher in the NADKD group compared the control group(all P<0.001) while the proportion of hypertension, systolic blood pressure, LDL-C, HbA 1C, and FPG were lower(all P<0.05). Multivariate linear regression analysis showed that eGFR was negatively associated with urea nitrogen and serum uric acid while positively associated with HbA 1C in normoalbuminuric elderly type 2 diabetic patients(all P<0.001). Logistic regression analysis revealed that hyperuricaemia was a risk factor for NADKD in elderly type 2 diabetic patients after adjusting for BMI, blood pressure, lipids, and glucose( OR=1.963, 95% CI 1.157-3.332, P=0.012). Conclusion:Hyperuricaemia is significantly associated with NADKD in elderly patients with type 2 diabetes.

Objective To investigate the popularization of cardiopulmonary resuscitation(CPR)knowledge and science popularization needs among urban and rural residents in Tonghai County,Yuxi City,Yunnan Province,so as to explore the establishment of an efficient and appropriate science popularization model.Methods A total of 300 residents aged 15-60 years old were selected from Tonghai County,Yuxi City,Yunnan Province using stratified and simple random sampling methods.A self-designed questionnaire was used to conduct an anonymous questionnaire survey.Results Only 20.3%of Tonghai County residents master CPR skills,and 26.2%of Tonghai County residents have never heard of CPR.There is a statistically significant difference in the awareness rate of CPR between rural residents and non-rural residents(P<0.01).There are differences in residents'age and CPR awareness(P<0.01),the age and CPR are inversely proportional.The residents have a higher willingness to perform chest compressions and mouth-to-mouth resuscitation on strangers,66.2%and 68.6%respectively.63.79%of residents have never attended relevant training.But 92.76%of the people said they were willing to participate in the relevant training when they learned the training news.Conclusion Residents in Tonghai County generally lack knowledge of CPR first aid,but the demand for first aid knowledge of residential CPR is high and the attitude towards rescue is positive.It is recommended that relevant departments increase CPR science popularization and training efforts,and popularize CPR into villages.

Objective:To investigate the effects of methyltransferases like 3(METTL3)mediated m6A modification of double homology cassette A pseudogene8(DUXAP8)on the proliferation,migration and invasion of salivary adenoid cystic carcinoma SACC-LM cells and its potential molecular mechanisms.Methods:Whole-transcriptome sequencing showed that DUXAP8 was highly ex-pressed in SACC than in para-cancerous tissues(P＜0.05).The m6A modification sites on DUXAP8 were predicted using the SRAMP website,and the mRNA and protein expression of m6A-modified genes and the genes associated with the epithelial-mesen-chymal transition(EMT)was measured by qRT-PCR and Western blot,respectively.METTL3 and DUXAP8 was knocked down or overexpressed in SACC-LM cells,and the proliferation,migration,and invasion of the cells were assessed by CCK-8,scratch and Transwell assays.The correlation between METTL3 and DUXAP8 was evaluated using MeRIP-qPCR.Results:The expression of DUXAP8 in SACC tumor was higher than that in para-cancerous tissues(P＜0.05).Knockdown of DUXAP8 reduced proliferation,migration and invasion of SACC-LM cells,as well as the expression of EMT-related genes(P＜0.05).Multiple m6A modification sites of high confidence were found on DUXAP8.METTL3 was highly expressed in tumor tissues,more than other related genes(P＜0.05)and enzyme-encoding genes in SACC-LM cells(P＜0.05).METTL3 was found to function as a methyltransferase to regulate the expression of DUX-AP8,and downregulation of METTL3 inhibited prolifera-tion,migration and invasion of SACC-LM cells and partially reversed the promotion of these activities induced by DUX-AP8 overexpression(P＜0.05).Conclusion:METTL3-me-diated m6A modification upregulated DUXAP8 expression,which promotes the proliferation,migration and invasion of SACC cells.

Objective To study the irradiation dose of organs at risk (OAR) in involved field radiation and extended field radiation in patients with thoracic esophageal cancer who received intensity modulated radiotherapy (IMRT). Methods A total of 40 patients with thoracic esophageal cancer were treated with IMRT. The involved field, extended field, and OAR were outlined to generate IMRT plans. The conformity index (CI) and homogeneity index (HI) of planning target volume (PTV) and the irradiation parameters of OAR were evaluated for the two plans. Paired t-test was used for comparison of irradiation parameters. Results The PTV of both plans received the prescribed dose. There were no significant differences in CI and HI of PTV between the two groups (P = 0.317, 0.130). There were significant differences in average lung dose, lung V₅, lung V₂₀, lung V₃₀, spinal cord D_mean, heart D_mean, heart D_max, heart V₃₀, heart V₄₀, and heart V₆₀ between the two groups (P < 0.01). Conclusion Compared with the extended field, the involved field can reduce the irradiation dose of ORA in patients with thoracic esophageal cancer, thus reducing the risk of radiation.

OBJECTIVE To evaluate the effectiveness and safety of sequential therapy with parathyroid hormone analogues and bisphosphonates for osteoporosis. METHODS PubMed， Embase， the Cochrane Library， Web of Science， China National Knowledge Infrastructure， VIP， Wanfang data， and SinoMed were searched in both English and Chinese databases from their inception to March 25， 2024. Two researchers independently conducted literature searches， screening， and data extraction. Review Manager 5.4 software was used for the meta-analysis. Subgroup analyses and sensitivity analyses were performed based on different medication sequences in the treatment group to account for potential sources of heterogeneity. RESULTS A total of 7 randomized controlled trials involving 2 461 participants were included， with 1 215 in the treatment group and 1 246 in the control group. The meta-analysis results showed that the treatment group using sequential therapy with parathyroid hormone analogues and bisphosphonates had superior effects on improving bone mineral density at the lumbar spine [SMD＝0.90， 95%CI （0.44， 1.35）， P＜0.001]， total hip [SMD=0.68， 95%CI （0.14， 1.21）， P＝0.01]， and femoral neck [SMD＝0.45， 95%CI （0.04， 0.86）， P＝0.03] compared to the control group. It also significantly outperformed the control group in reducing the incidence of fractures post- treatment [OR＝0.72， 95%CI （0.54， 0.97）， P＝0.03].significant difference was noted in the incidence of adverse reactions between the two groups [OR＝1.21， 95%CI （0.99， 1.46）， P＝0.06]. Subgroup analysis based on intervention measures in the treatment group showed that switching from bisphosphonates to parathyroid hormone analogues [SMD＝0.56， 95%CI （0.09， 1.03）， P＝0.02] or switching from parathyroid hormone analogues to bisphosphonates [SMD＝0.97， 95%CI （0.49， 1.46）， P＜0.001] both significantly potentiated lumbar spine bone mineral density compared to the control group. Switching from bisphosphonates to parathyroid hormone analogues also significantly promoted total hip bone mineral density compared to the control group [SMD＝0.66， 95%CI （0.18， 1.13）， P＝0.007]. Sensitivity analysis indicated that the results of this study were robust. CONCLUSIONS Sequential therapy with parathyroid hormone analogues and bisphosphonates can be recommended as an effective treatment for patients with osteoporosis， with good safety profiles. The medication sequences should be individually adjusted based on the patient’s particular situation and the different responses of various skeletal sites.