Objective To assess the status and severity of bone disease in patients with multiple myeloma (MM) by using chest computerized tomography (CT) and the relationship between clinical prognostic parameters and bone disease.Methods All 46 newly diagnosed MM in-patients received both imaging tests of chest CT and plain X ray.An experienced radiologist reviewed all the imaging data.Clinical laboratory parameters,stages of Durie-Salmon (DS) and International Staging System (ISS) were evaluated.Five cytogenetic abnormalities of bone marrow myeloma cells were tested by fluorescence in situ hybridization (FISH).Results The sensitivity of CT and X ray to determine pathological fractures was comparable,the positive rates of which were 41.3％ (19/46) and 30.4％ (14/46) respectively (P =0.29).Nevertheless,the positive rate of osteolytic lesions ascertained by CT was significantly higher than that by X ray (P ＜ 0.001),60.9％ (28/46) vs 13.0％ (6/46) with diameter 5-10 mm and 50.0％ (23/46) vs 10.9％ (5/ 46) with diameter more than 10 mm.Osteolytic lesion numbers found by CT were more than those by X ray [5(0-21) vs0(0-4) lesions with diameter5-10 mm (P＜0.001),2(0-14) vs0(0-2) lesions with diameter more than 10 mm (P ＜ 0.001),respectively].Patients with positive osteolytic lesions had higher percentage of RB1 gene deletion[46.7％ (14/30) vs 18.8％ (3/16),P ＜0.001],D13s319 deletion [43.3％ (13/30) vs 18.8％ (3/16),P ＜0.001] and high risk cytogenetic abnormalities[50.0％ (15/30) vs 25.0％ (4/16),P ＜ 0.001].Conclusions Chest CT is more sensitive than plain X ray in detecting osteolytic myeloma bone disease.Osteolysis determined by CT is relevant to clinical DS stages and risk stratification of cytogenetic abnormalities.

Objective To evaluate the metabolite pattern and the severity in patients with spinocerebellar ataxia type 3/ Machado-Joseph disease (SCA3/MJD) by 1H magnetic resonance spectroscopy (1H-MRS) on different cerebellar regions, including cerebellar vermis, cerebellar peduncles, cerebellar cortex, and dentatum. Methods Thirty-six SCA3/MJD patients, and 27 sex, age-matched healthy controls were scanned with 1H-MRS for N-acetylaspartate (NAA), choline (Cho) and creatine (Cr). We made cerebellar vermis, cerebellar peduncles, cerebellar cortex, and dentatum as the region of interests (ROI), and finally got access to NAA/Cr, Cho/Cr, and NAA/Cho ratios. We also examined the CAG repeat numbers of MJD1 gene, scored the 36 patients by the scale for the assessment and rating of ataxia (SARA), analyzed the differences in ratios between SCA3/MJD patients and the control group, and explored whether relevance existed between these ratios and duration of the disease, age of onset, CAG repeat times, and SARA scores respectively. Results The ratio of NAA/Cr in SCA3/MJD patients showed a significant reduction in the cerebellar cortex, dentatum, cerebellar vermis and medipeduncle (P<0.01) compared with the controls. The ratio of NAA/Cho also showed significant reduction in the dentatum and cerebellar vermis (P<0.01). A number of correlations were found between the metabolite ratios of 1H-MRS and duration of the disease, age of onset, expanded CAG and SARA score in SCA3/MJD patients. Conclusion 1H-MRS, which shows the neural metabolic changes in the cerebella of SCA3/MJD patients, provides useful information about the severity of SCA3/MJD.

OBJECTIVETo study the single-nucleotide substitution (c.-16C to T) of the PURATROPHIN-1 gene in spinocerebellar ataxia (SCA) patients in China.

METHODSThe single-nucleotide substitution (c.-16C to T) of the PURATROPHIN-1 gene was detected by PCR, digested with EcoN I, separated on 8% polyacrylamide gel in 68 probands of autosomal dominant SCA families and 119 sporadic SCA patients, who had been excluded CAG/CAA repeat expansion at the SCA1, 2, 3, 6, 7, 17 and dentatorubral-pallidolluysian atrophy (DRPLA) loci. The results were confirmed in four patients by direct sequencing.

RESULTSThe single-nucleotide substitution (c.-16C to T) of the PURATROPHIN-1 gene was not identified in authors' cohort.

CONCLUSIONThe mutation of c.-16C to T of the PURATROPHIN-1 gene might be rare in SCA patients in China.

Asian Continental Ancestry Group ; genetics ; Cohort Studies ; Guanine Nucleotide Exchange Factors ; genetics ; Humans ; Mutation ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Spectrin ; genetics ; Spinocerebellar Ataxias ; genetics

Aspirin is a kind of anti-inflammatory drug and may be used to reverse hyperglycemia, hyperinsulinemia, and dyslipidemia by improving insulin resistance. We hypothesized that aspirin improves insulin resistance in type 2 diabetes by inhibiting hepatic nuclear factor kappa-beta (NF-kappaB) activation and serum tumor necrosis factor-alpha (TNF-alpha). Adult male Wistar rats were randomly divided into four groups: control, untreated diabetic, diabetic treated with metformin (100 mg/kg/day), and diabetic treated with aspirin (120 mg/kg/day). Diabetes was induced by high-fat feeding and a low dose of streptozotocin (30 mg/kg). After treatment, plasma glucose, insulin, lipids, free fatty acids (FFAs) concentrations and serum TNF-alpha were determined. The expression of NF-kappaB in hepatocytes was analyzed by immunohistochemistry and western blot. The results showed administration of aspirin caused no significant lowering in fasting glucose level but significant reduction of hepatic NF-kappaB expression and serum TNF-alpha level with improved insulin resistance compared to the diabetic group. The relevant analysis showed positive correlation between the expression of homeostasis model assessment-insulin resistance (HOMA-IR) and NF-kappaB (r = 0.799, P < 0.01); HOMA-IR and serum TNF-alpha (r = 0.790, P < 0.01). It is concluded that aspirin improves insulin resistance by inhibiting hepatic NF-kappaB activation and TNF-alpha level in streptozotocin-induced type 2 diabetic rats.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*pharmacology ; Aspirin/*pharmacology ; Blood Glucose/analysis ; Diabetes Mellitus, Experimental/blood/chemically induced/*metabolism ; Fatty Acids, Nonesterified/blood ; Hypoglycemic Agents/*pharmacology ; Insulin/blood ; Insulin Resistance ; Liver/metabolism ; Male ; Metformin/therapeutic use ; NF-kappa B/*metabolism ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha/*blood

Objective To assess the frequency of different subtype of spinocerebellar ataxias (SCAs) in Chinese Han population. Methods The nueleotide repeat mutations of SCA1, SCA2, SCA3/ MJD, SCA6, SCAT, SCA8, SCA10, SCA12, SCA17 and dentatorubral-pallidoluysian atrophy (DRPLA) were detected by the polymerase chain reaction (PCR), denaturing polyacrylamide gel electrophoresis (PAGE), Southern blot, recombinant DNA technology by T-vector cloning and direct sequencing technique in a cohort of 559 Mainland Chinese patients affected by spinocerebellar ataxia, including 363 families with autosomal dominant SCA (AD-SCA) and 196 sporadic cases. Results Among the 363 AD-SCA families, 15 families (4. 13%) were positive for SCA1, 26 (7. 16%) for SCA2, 187 (51.52%) for SCA3/MJD, 6 (1.65%) for SCA6, 7 (1.93%) for SCA7, 1 (0. 28%) for SCA12 and 1 (0. 28%) positive for SCA17; 120(33. 06%) were negative for all the tested SCAs. There were 2 (1.02%) SCAI, 3 (1.53%) SCA2, 15 (7. 65%) SCA3/MJD, 3 (1.53%) SCA6 and 173 (88.27%) not identified in the 196 sporadic SCA patients. None of the SCA8, SCA10 and DRPLA mutation was found. Conclusions SCA3/MJD is a substantially common subtype of AD-SCAs and sporadic SCA in Chinese Han patients with SCAs, subsequently followed by SCA2, SCA1, SCAT and SCA6; SCA12 and SCA17 are uncommon subtypes, while SCA8, SCA10, and DRPLA are rare, if not absent. SCA17 subtype was initially identified in mailand China. Some other genes might be causative in those unidentified AD-SCA pedigrees, and other etiological factors besides genetic cause might contribute for those sporadic cases.

OBJECTIVETo investigate the CAG trinucleotide repeat expansion in spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7, 12, and 17 from Chinese Han.

METHODSThe pathological CAG triplet repeat expansions of the SCA1, SCA2, SCA3/Machado-Joseph disease (MJD), SCA6, SCA7, SCA12 and SCA17 genes were analyzed in a cohort of 559 Mainland Chinese patients affected by spinocerebellar ataxia, including 363 probands from families with autosomal dominant SCA and 196 sporadic cases. Polymerase chain reaction, agarose gel electrophoresis, recombinant DNA technology by T-vector cloning and direct sequencing were performed to detect the CAG-repeat number of abnormal allele.

RESULTSAmong the 559 SCA patients, twenty-three were positive for SCA1, the ranges of expanded CAG repeats were from 39 to 60 (mean:51.09+/-4.88); thirty-two were positive for SCA2, the ranges of expanded CAG repeats were from 36 to 51 (mean:40.34+/-4.40); three hundred and five were positive for SCA3/MJD, the ranges of expanded CAG repeats were from 49 to 86 (mean:73.84+/-5.07); nine were positive for SCA6, the ranges of expanded CAG repeats were from 23 to 29 (mean:25.56+/-1.94); twenty-seven were positive for SCA7, the ranges of expanded CAG repeats were from 38 to 71(mean:58.22+/-10.90); three were positive for SCA12, the ranges of expanded CAG repeats were from 51 to 52 (mean:51.33+/-0.58); and finally, two were positive for SCA17, the range of expanded CAG repeats were from 53 to 55 (mean:54.00+/-1.41).

CONCLUSIONThe 39 CAG repeats of SCA1, 49 CAG repeats of SCA3 and 51 CAG repeats of SCA12 are all the shortest known causative expanded alleles, while the 86 CAG repeats of SCA3/MJD is the largest full expanded allele that has never been reported. Furthermore, it is the first report of SCA17 subtype in Mainland Chinese and first research that established the abnormal reference standard of CAG repeat number of different subtypes of SCA in Chinese Han.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; ethnology ; genetics ; Ataxin-7 ; Ataxins ; Base Sequence ; Child ; Child, Preschool ; Cohort Studies ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Nerve Tissue Proteins ; genetics ; Protein Phosphatase 2 ; genetics ; Spinocerebellar Ataxias ; ethnology ; genetics ; Trinucleotide Repeat Expansion ; Young Adult

Objective:To evaluate the efficacy and safety of comprehensive treatment based on radiotherapy for patients with leptomeningeal metastases (LM) in this prospective study.Methods:A total of 93 patients diagnosed with LM admitted to our hospital undergoing whole brain radiotherapy (WBRT) or craniospinal irradiation (CSI) with or without simultaneous boost from 2014 to 2017 were enrolled. The dynamic changes of clinical signs and symptoms, enhanced magnetic resonance imaging (MRI), cerebrospinal fluid cytology and liquid biopsy detection were recorded. The primary endpoint was overall survival (OS), the secondary endpoints were local control (LC), intracranial progress-free survival (IPFS), brain metastasis specific survival (BMSS) and toxicity.Results:The major primary disease was non-small cell lung cancer. The whole cohort received WBRT with boost (40 Gy in 20 fractions (f) for WBRT and 60 Gy in 20 f for boost), focal radiation to LM, WBRT and CSI (40 Gy in 20 f or 50 Gy in 25 f for WBRT and 36 Gy in 20 f for CSI). For 20 patients, tumor cells were identified and intrathecal chemotherapy was performed. Sixty-three patients received target therapy. The median follow-up time was 33.8 months. The 1-year OS, LC and IPFS was 62.4%, 77.2% and 52.6%, respectively. The median survival time was 15.9 months, and the median BMSS was 42.2 months. Treatment-related grade 3-4 adverse events were rare and only 8 cases was observed to have grade 3 hematological toxicity.Conclusion:Reasonable comprehensive treatment including precise radiotherapy, intrathecal chemotherapy and targeted therapy can be well tolerated and prolong the survival time of LM patients.

Objective:To investigate the interactive effect of mismatch repair (MMR) protein status and adverse clinicopathological features on prognosis of stage Ⅰ-Ⅲ colon cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 650 patients with colon cancer of stage Ⅰ-Ⅲ who were admitted to 7 hospitals in China from January 2016 to December 2017 were collected. There were 963 males and 687 females, aged 62(53,71)years. Patients were classified as 230 cases of MMR deficiency (dMMR) and 1 420 cases of MMR proficiency (pMMR) based on their MMR protein status. Observation indicators: (1) comparison of clinicopathological characteristics between patients of different MMR protein status; (2) analysis of factors affecting the survival outcomes of patients of dMMR; (3) analysis of factors affecting the survival outcomes of patients of pMMR; (4) interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The random forest interpolation method was used for missing values in data interpolation. Univariate analysis was conducted using the COX proportional risk regression model, and multivariate analysis was conducted using the COX stepwise regression with forward method. The coefficient of multiplication interaction effect was obtained using the interaction term coefficient of COX proportional risk regression model. Evaluation of additive interaction effects was conducted using the relative excess risk due to interaction ( RERI). Results:(1) Comparison of clinicopathological characteristics between patients of different MMR protein status. There were significant differences in age, T staging, the number of lymph node harvest, the number of lymph node harvest <12, high grade tumor between patients of dMMR and pMMR ( P<0.05). (2) Analysis of factors affecting the survival outcomes of patients of dMMR. Results of multivariate analysis showed that T staging, N staging, the number of lymph node harvest <12 were independent factors affecting the disease-free survival (DFS) of colon cancer patients of dMMR ( hazard ratio=3.548, 2.589, 6.702, 95% confidence interval as 1.460-8.620, 1.064-6.301, 1.886-23.813, P<0.05). Age and N staging were independent factors affecting the overall survival (OS) of colon cancer patients of dMMR ( hazard ratio=1.073, 10.684, 95% confidence interval as 1.021-1.126, 2.311-49.404, P<0.05). (3) Analysis of factors affecting the survival outcomes of patients of pMMR. Results of multivariate analysis showed that age, T staging, N staging, vascular tumor thrombus were independent factors affecting the DFS of colon cancer patients of pMMR ( hazard ratio=1.018, 2.214, 2.598, 1.549, 95% confidence interval as 1.006-1.030, 1.618-3.030, 1.921-3.513, 1.118-2.147, P<0.05). Age, T staging, N staging, high grade tumor were independent factors affecting the OS of colon cancer patients of pMMR ( hazard ratio=1.036, 2.080, 2.591, 1.615, 95% confidence interval as 1.020-1.052, 1.407-3.075, 1.791-3.748, 1.114-2.341, P<0.05). (4) Interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Results of interaction analysis showed that the multiplication interaction effect between the number of lymph node harvest <12 and MMR protein status was significant on DFS of colon cancer patients ( hazard ratio=3.923, 95% confidence interval as 1.057-14.555, P<0.05). The additive interaction effects between age and MMR protein status, between high grade tumor and MMR protein status were significant on OS of colon cancer patients ( RERI=-0.033, -1.304, 95% confidence interval as -0.049 to -0.018, -2.462 to -0.146). Conclusions:There is an interaction between the MMR protein status and the adverse clinicopathological features (the number of lymph node harvest <12, high grade tumor) on prognosis of colon cancer patients of stage Ⅰ-Ⅲ. In patients of dMMR, the number of lymph node harvest <12 has a stronger predictive effect on poor prognosis. In patients of pMMR, the high grade tumor has a stronger predictive effect on poor prognosis.

ObjectiveTo investigate the trends in diabetes mortality and potential years of life lost (PYLL) among residents of Huangpu District, Shanghai from 1993 to 2021, to analyze the long-term trends of diabetic patients with different characteristics and to provide a reference for scientific prevention and control of diabetes in aging urban areas. MethodsDiabetes mortality data were obtained from the Huangpu District cause of death registration records in the Shanghai death cause registration system. Indicators such as crude mortality rate, standardized mortality rate, potential years of life lost (PYLL), average years of life lost (AYLL), annual percentage change (APC), and average annual percentage change (AAPC) were used to analyze diabetes-related mortality and life loss. Statistical analyses were performed using software SPSS 21.0 and Joinpoint 5.0.2. ResultsFrom 1993 to 2021, the average annual crude mortality rate of diabetes in Huangpu District was 46.56/100 000, and the average annual standardized mortality rate was 20.44/100 000. The crude mortality rate and standardized mortality rate of diabetes for female residents were higher than those for males. The crude mortality rate showed an overall increasing trend [AAPC=2.81% (95%CI: 0.20%‒5.49%), P<0.05], while the increase in standardized mortality rate significantly slowed [AAPC=0.15% (95%CI: -2.27%‒2.63%)], P<0.05]. The mortality rate rose rapidly in the 70‒74 years age group and peaked in the 85‒ years age group (607.69/100 000). Diabetes accounted for a cumulative PYLL of22 741 person-years, with an average annual AYLL of 1.88 years and an average annual potential years of life lost rate (PYLLR) of 0.82‰. Male residents had higher PYLL, AYLL, and PYLLR than females. ConclusionDiabetes mortality rates in Huangpu District have increased year by year, resulting in significant life loss. However, the age-standardized mortality rate increase has markedly slowed. Efforts should focus on elderly diabetic patients aged ≥70 years, by leveraging platforms such as community-based chronic disease health support centers, efforts should be made to enhance diabetes screening service for middle-aged and elderly residents. Consequently, elderly diabetic patients’ awareness of diabetes and responce to related complications is improved, which would be conducive to controling the progression of complications and reducing the mortolity risk of diabetes.

Humans ; Severe Acute Respiratory Syndrome ; diagnosis ; therapy