Clinical value of the MeltPro MTB assays in detection of drug-resistant tuberculosis in paraffin-embedded tissues / 中华病理学杂志

Objective: To evaluate the clinical value of the MeltPro MTB assays in the diagnosis of drug-resistant tuberculosis. Methods: A cross-sectional study design was used to retrospectively collect all 4 551 patients with confirmed tuberculosis between January 2018 and December 2019 at Beijing Chest Hospital, Capital Medical University. Phenotypic drug sensitivity test and GeneXpert MTB/RIF (hereafter referred to as "Xpert") assay were used as gold standards to analyze the accuracy of the probe melting curve method. The clinical value of this technique was also evaluated as a complementary method to conventional assays of drug resistance to increase the detective rate of drug-resistant tuberculosis. Results: By taking the phenotypic drug susceptibility test as the gold standard, the sensitivity of the MeltPro MTB assays to detect resistance to rifampicin, isoniazid, ethambutol and fluoroquinolone was 14/15, 95.7%(22/23), 2/4 and 8/9,respectively; and the specificity was 92.0%(115/125), 93.2%(109/117), 90.4%(123/136) and 93.9%(123/131),respectively; the overall concordance rate was 92.1%(95%CI:89.6%-94.1%),and the Kappa value of the consistency test was 0.63(95%CI:0.55-0.72).By taking the Xpert test results as the reference, the sensitivity of this technology to the detection of rifampicin resistance was 93.6%(44/47), the specificity was100%(310/310), the concordance rate was 99.2%(95%CI:97.6%-99.7%), and the Kappa value of the consistency test was 0.96(95%CI:0.93-0.99). The MeltPro MTB assays had been used in 4 551 confirmed patients; the proportion of patients who obtained effective drug resistance results increased from 83.3% to 87.8%(P<0.01); and detection rate of rifampicin, isoniazid, ethambutol, fluoroquinolone resistance, multidrug and pre-extensive drug resistance cases were increased by 3.2%, 14.7%, 22.2%, 13.7%, 11.2% and 12.5%, respectively. Conclusion: The MeltPro MTB assays show satisfactory accuracy in the diagnosis of drug-resistant tuberculosis. This molecular pathological test is an effective complementary method in improving test positivity of drug-resistant tuberculosis.

A nomogram for preoperative prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma based on inflammation-related markers / 中华外科杂志

Objectives: To construct a nomogram for prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis based on inflammation-related markers,and to conduct its clinical verification. Methods: Clinical and pathological data of 858 ICC patients who underwent radical resection were retrospectively collected at 10 domestic tertiary hospitals in China from January 2010 to December 2018. Among the 508 patients who underwent lymph node dissection,207 cases had complete variable clinical data for constructing the nomogram,including 84 males,123 females,109 patients≥60 years old,98 patients<60 years old and 69 patients were pathologically diagnosed with positive lymph nodes after surgery. Receiver operating characteristic curve was drawn to calculate the accuracy of preoperative imaging examinations to determine lymph node status,and the difference in overall survival time was compared by Log-rank test. Partial regression squares and statistically significant preoperative variables were screened by backward stepwise regression analysis. R software was applied to construct a nomogram,clinical decision curve and clinical influence curve,and Bootstrap method was used for internal verification. Moreover,retrospectively collecting clinical information of 107 ICC patients with intraoperative lymph node dissection admitted to 9 tertiary hospitals in China from January 2019 to June 2021 was for external verification to verify the accuracy of the nomogram. 80 patients with complete clinical data but without lymph node dissection were divided into lymph node metastasis high-risk group and low-risk group according to the score of the nomogram among the 858 patients. Log-rank test was used to compare the overall survival of patients with or without lymph node metastasis diagnosed by pathology. Results: The area under the curve of preoperative imaging examinations for lymph node status assessment of 440 patients was 0.615,with a false negative rate of 62.8% (113/180) and a false positive rate of 14.2% (37/260). The median survival time of 207 patients used to construct a nomogram with positive or negative postoperative pathological lymph node metastases was 18.5 months and 27.1 months,respectively (P<0.05). Five variables related to lymph node metastasis were screened out by backward stepwise regression analysis,which were combined calculi,neutrophil/lymphocyte ratio,albumin,liver capsule invasion and systemic immune inflammation index,according to which a nomogram was constructed with concordance index(C-index) of 0.737 (95%CI: 0.667 to 0.806). The C-index of external verification was 0.674 (95%CI:0.569 to 0.779). The calibration prediction curve was in good agreement with the reference curve. The results of the clinical decision curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.32,the maximum net benefit could be obtained by 0.11,and the cost/benefit ratio was 1∶2. The results of clinical influence curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.6,the probability of correctly predicting lymph node metastasis could reach more than 90%. There was no significant difference in overall survival time between patients with high/low risk of lymph node metastasis assessed by the nomogram and those with pathologically confirmed lymph node metastasis or without lymph node metastasis (Log-rank test:P=0.082 and 0.510,respectively). Conclusion: The prediction accuracy of preoperative nomogram for ICC lymph node metastasis based on inflammation-related markers is satisfactory,which can be used as a supplementary method for preoperative diagnosis of lymph node metastasis and is helpful for clinicians to make personalized decision of lymph node dissection for patients with ICC.

Survival analysis of patients with intrahepatic cholangiocarcinoma treated with adjuvant chemotherapy after radical resection based on CoxPH model and deep learning algorithm / 中华外科杂志

Objective: To establish a predictive model for survival benefit of patients with intrahepatic cholangiocarcinoma (ICC) who received adjuvant chemotherapy after radical resection. Methods: The clinical and pathological data of 249 patients with ICC who underwent radical resection and adjuvant chemotherapy at 8 hospitals in China from January 2010 to December 2018 were retrospectively collected. There were 121 males and 128 females,with 88 cases>60 years old and 161 cases≤60 years old. Feature selection was performed by univariate and multivariate Cox regression analysis. Overall survival time and survival status were used as outcome indicators,then target clinical features were selected. Patients were stratified into high-risk group and low-risk group,survival differences between the two groups were analyzed. Using the selected clinical features, the traditional CoxPH model and deep learning DeepSurv survival prediction model were constructed, and the performance of the models were evaluated according to concordance index(C-index). Results: Portal vein invasion, carcinoembryonic antigen>5 μg/L,abnormal lymphocyte count, low grade tumor pathological differentiation and positive lymph nodes>0 were independent adverse prognostic factors for overall survival in 249 patients with adjuvant chemotherapy after radical resection (all P<0.05). The survival benefit of adjuvant chemotherapy in the high-risk group was significantly lower than that in the low-risk group (P<0.05). Using the above five features, the traditional CoxPH model and the deep learning DeepSurv survival prediction model were constructed. The C-index values of the training set were 0.687 and 0.770, and the C-index values of the test set were 0.606 and 0.763,respectively. Conclusion: Compared with the traditional Cox model, the DeepSurv model can more accurately predict the survival probability of patients with ICC undergoing adjuvant chemotherapy at a certain time point, and more accurately judge the survival benefit of adjuvant chemotherapy.

Exploring the significance of chemotherapy in the perioperative application of biliary tract carcinomas / 中华外科杂志

Biliary tract cancer is extremely malignant with a poor prognosis. At the moment, the only curative method available is radical resection. Targeted and immunotherapy are currently advancing quickly, but chemotherapy still holds a key role in the perioperative management of biliary cancer. Perioperative chemotherapy aims to decrease tumor volume before surgery so that patients can have their tumors surgically removed or have a higher radical resection rate. It also aims to remove any tumor cells that remain after surgery and prevent the growth of new tumors. Chemotherapy-based combination treatment techniques have been increasingly investigated in recent years to improve perioperative care and patient survival. From the standpoint of chemotherapy regimens and clinical trial success in the perioperative phase of radical surgery, the value of chemotherapy in the perioperative period of biliary tract cancer were explored in this paper.

Clinical diagnosis and treatment of primary thyroid tuberculosis: a retrospective study

ABSTRACT BACKGROUND: Primary thyroid tuberculosis (PTT) is an uncommon type of extrapulmonary tuberculosis, which is caused by Mycobacterium tuberculosis. It does not have specific clinical manifestations, and most cases are diagnosed through postoperative histopathological examination. OBJECTIVE: To evaluate the diagnostic pattern and management strategy among patients with primary thyroid tuberculosis. DESIGN AND SETTING: Retrospective study on patients with primary thyroid tuberculosis in the First Hospital of Jilin University (Changchun, China). METHODS: Between March 2015 and June 2020, nine cases of PTT were diagnosed and treated in the Department of Thyroid Surgery of the First Hospital of Jilin University. Age at diagnosis, primary symptoms, preoperative biopsy, operation method, pathological classification, acid-fast staining test, anti-TB therapy and prognosis were registered in order to explore the appropriate protocol for diagnosis and treatment of this disease. RESULTS: None of the patients was diagnosed with thyroid tuberculosis before surgery. All the patients underwent surgery. Granulomatous changes or caseous necrosis in thyroid tissue were found through postoperative histopathological evaluation. Polymerase chain reaction (PCR) results for Mycobacterium tuberculosis were positive in all patients. Most patients had a good prognosis after surgery and anti-tuberculosis drug therapy. CONCLUSION: PTT is a rare disease. It is important to improve the preoperative diagnosis. Preoperative diagnostic accuracy relies on increased awareness of the disease and appropriate use of preoperative diagnostic methods, such as PCR detection, fine-needle aspiration cytology, acid-fast bacillus culture, ultrasound and blood sedimentation. PCR detection of M. tuberculosis is recommended as the gold standard for diagnosis.

Significance of combination of targeted therapy and immunotherapy in conversion therapy of biliary tract cancer / 中华外科杂志

Biliary tract cancer has insidious onset and high degree of malignancy, and radical resection is often impossible when it is diagnosed.Conversion therapy can achieve tumor downgrading, so that patients who were initially unresectable have a chance to achieve R0 resection.However, due to the high heterogeneity and complex immune microenvironment of biliary tract cancer, conversion therapy is still in the stage of active exploration.As a new type of conversion therapy, combination of targeted therapy and immunotherapy is of great significance to effectively improve the efficiency of conversion therapy.Further exploration of combination mechanism and improvement of immune microenvironment are expected to become the future direction of combination of targeted therapy and immunotherapy.

Association between the Neutrophil-to-lymphocyte Ratio and New-onset Subclinical Macrovascular and Microvascular Diseases in the Chinese Population / 生物医学与环境科学（英文）

OBJECTIVE@#The association between neutrophil-to-lymphocyte ratio (NLR) with subclinical macrovascular and microvascular diseases has been less investigated. We sought to examine the association between NLR and new-onset subclinical macrovascular and microvascular abnormalities in the Chinese population.@*METHODS@#From a community cohort, we included 6,430 adults aged ≥ 40 years without subclinical macrovascular and microvascular diseases at baseline. We measured subclinical macrovascular and microvascular abnormalities separately using the ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), and albuminuria.@*RESULTS@#During a mean follow-up of 4.3 years, 110 participants developed incident abnormal ABI, 746 participants developed incident elevated baPWV, and 503 participants developed incident albuminuria. Poisson regression analysis indicated that NLR was significantly associated with an increased risk of new-onset abnormal ABI, elevated baPWV, and albuminuria. Compared to overweight/obese participants, we found a much stronger association between NLR and subclinical vascular abnormalities in participants with normal weight. Furthermore, we found an interaction between the NLR and body mass index (BMI) on the risk of new-onset abnormal ABI ( P for interaction: 0.01).@*CONCLUSION@#NLR was associated with subclinical macrovascular and microvascular diseases in the Chinese population. Furthermore, in participants with normal weight, the association between NLR and subclinical vascular abnormalities was much stronger.

Multi-index components of Scutellariae Barbatae Herba according to UHPLC-QTRAP-MS coupled with chemometrics / 中国中药杂志

The present study developed an ultra-fast liquid chromatography coupled with triple quadrupole-linear ion trap composite mass spectrometry(UHPLC-QTRAP-MS) to simultaneously determine the content of potential active components in Scutellariae Barbatae Herba and also to provide a reference approach for screening out the differential quality control components among different batches of Scutellariae Barbatae Herba. Chromatographic separations were conducted on a Thermo Acclaim~(TM) RSLC 120 C_(18) column(3.0 mm×100 mm, 2.2 μm) in a gradient program. The mobile phase consisted of 0.1% aqueous formic acid and acetonitrile, and the column temperature was maintained at 40 ℃. The flow rate was 0.4 mL·min~(-1) and the injection volume was 2 μL. The targeted compounds were monitored in the multiple reaction monitoring(MRM) mode. The acquired data were processed by hierarchical cluster analysis(HCA) and partial least square discriminant analysis(PLS-DA). Sixteen compounds all showed good linear relationship within the corresponding linear ranges and the R~2 values were all higher than 0.993 2. The RSDs of precision, repeatability, and stability were less than or equal to 3.7%. Mean recovery rates were in the range of 95.67% and 104.8% with RSDs≤3.2%. According to HCA and PLS-DA, all samples were clustered into four categories. Scutellarin, acteoside, scutellarein, and scutebarbatine X(VIP>1) were considered as differential chemical markers in the four categories. In conclusion, the developed method can be used for the simulta-neous determination of the multiple components and quality control of Scutellariae Barbatae Herba.

Long-term Effect of Sling-massage Exercise on Cervical Spondylopathy / 中国康复理论与实践

Objective:To explore the effect of sling-massage exercise on neck type cervical spondylopathy (NTCS). Methods:From June, 2020 to February, 2021, 68 patients with NTCS from the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine were randomly divided into control group (n = 34) and observation group (n = 34). The control group accepted routine massage, while the observation group accepted sling exercise and massage based on weak link test, for four weeks. They were assessed with McGill Pain Qusetionnaire (MPQ) and Neck Disability Index (NDI) before and after treatment, and measured median frequency (MF) of the upper trapezius muscle on the affected side with electromyography biofeedback before treatment, after treatment, two weeks after treatment and 4 weeks after treatment. Results:Four cases in the control group and three cases in the observation group dropped down. The scores of MPQ and NDI decreased in both groups after treatment (|Z| > 4.879, P < 0.001), while MF increased (P < 0.001). There was no significant difference in scores of MPQ and NDI between the two groups after treatment (|Z| < 1.100, P > 0.05), while MF was less in the control group than in the observation group (t = 2.184, P < 0.05). MF decreased more in the control group than in the observation group, and was continually less in the control group than in the observation group after treatment (t > 3.770, P < 0.001). Conclusion:Sling-massage exercise is as effective as massage on NTCS immediately, and for more time.

Preparation and anti-tumor activity of a novel antibody-drug conjugate 607-LDM / 药学学报

Antibody-drug conjugates (ADCs) are one of the most important classes of anticancer therapeutics. Human epidermal growth factor receptor-2 (HER2), which is highly expressed in many types of aggressive cancers including breast and ovarian cancer, has been approved as an ideal target for ADCs. Lidamycin (LDM), developed by Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, is an enediyne-containing antibiotic with potent anti-tumor activity. LDM is a promising payload for ADCs. In the present research, using a special site-directed conjugating technology, we made a novel ADC (607-LDM) with a drug-to-antibody ratio (DAR) of 2 and composed of the anti-HER2 antibody 607 and LDM. The new ADC exhibited potent antitumor activity against human ovarian cancer SKOV3 and breast cancer BT-474 cells. It also induced apoptosis and G2/M arrest. In nude mice with SKOV3 xenografts and a tumor volume of 150-200 mm3, a single intravenous injection 607-LDM at 1 mg·kg-1 induced tumor growth inhibition of 72.4%, which was significant compared to either LDM (50.6%) or antibody (30.2%) treatment alone, or both in combination (50.1%, P < 0.05). All animal experiments were performed in accord with National Regulations and approved by the Animal Experiments Ethical Committee of College of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences. The novel ADC designed in this study, 607-LDM, is a promising candidate for the treatment of HER2-positive cancers.

A genotyping study of 13 cases of early-onset Charcot-Marie-Tooth disease / 中国当代儿科杂志

OBJECTIVE@#To study the clinical characteristics and genetic variation of early-onset Charcot-Marie-Tooth disease (CMT).@*METHODS@#Children with a clinical diagnosis of early-onset CMT were selected for the study. Relevant clinical data were collected, and electromyogram and CMT-related gene detection were performed and analyzed.@*RESULTS@#A total of 13 cases of early-onset CMT were enrolled, including 9 males (69%) and 4 females (31%). The mean age at consultation was 4.0±2.1 years. Among them, 12 children (92%) had an age of onset less than 2 years, 9 children (69%) were diagnosed with CMT type 1 (including 6 cases of Dejerine-Sottas syndrome), 1 child (8%) with intermediate form of CMT, and 3 children (23%) with CMT type 2. The genetic test results of these 13 children showed 6 cases (46%) of PMP22 duplication mutation, 3 cases (23%) of MPZ gene insertion mutation and point mutation, 3 cases (23%) of MFN2 gene point mutation, and 1 case (8%) of NEFL gene point mutation. Eleven cases (85%) carried known pathogenic mutations and 2 cases (15%) had novel mutations. The new variant c.394C>G (p.P132A) of the MPZ gene was rated as "possibly pathogenic" and the new variant c.326A>G (p.K109R) of the MFN2 gene was rated as "pathogenic".@*CONCLUSIONS@#Early-onset CMT is mainly caused by PMP22 gene duplication mutation and MPZ gene mutations. The clinical phenotype is mainly CMT type 1, among which Dejerine-Sottas syndrome accounts for a considerable proportion.

Preparation of Co-amorphous Curcumin-tryptophan and Its Pharmacokinetic Study in Rats / 中国药房

OBJECTIVE：To prepare Co-amorphous curcumin （CUR）-tryptophan （TRY） （Co-amorphous CUR-TRY）， and to study its pharmacokinetic characteristics in rats. METHODS： Co-amorphous CUR-TRY was prepared by ball milling method. differential scanning calorimetry （DSC） and powder X-ray diffraction （XRD） were used to characterize Co-amorphous CUR-TRY. The in vitro dissolution rate （dissolution） of Co-amorphous CUR-TRY， CUR and CUR-TRY physical mixture were compared under sink condition and non-sink condition. 18 SD rats were selected and randomly divided into Co-amorphous CUR-TRY group （155.43 mg/kg）， CUR raw material group （100 mg/kg）， CUR-TRY physical mixture group （155.43 mg/kg）， with 6 rats in each group. They were given relevant medicine intragastrically once. Each blood samples 0.3 mL were collected from orbital venous plexus 0.167， 0.33， 0.5， 0.75， 1， 1.5， 2， 4， 6， 8， 10， 12， 24 h after medication. UPLC-MS/MS was used to determine plasma concentration of CUR in rats. The pharmacokinetic study was performed by using DAS 3.0 software. RESULTS： DSC and XRD showed that Co-amorphous CUR-TRY was successfully prepared. Under sink condition （120 min）， compared with CUR raw material [cumulative dissolution rate of CUR is （36.79±3.79）％] and CUR-TRY physical mixture [cumulative dissolution rate of CUR is （33.12±0.68）％]， cumulative dissolution rate of CUR in Co-amorphous CUR-TRY （90.37±2.52）％ was improved significantly （P＜0.01）. Under non-sink condition， compared with CUR raw material and CUR-TRY physical mixture， CUR of Co-amorphous CUR-TRY exhibited  dissolution and maintained supersaturation for a long time. Pharmacokinetic study showed that compared with CUR raw material group and CUR-TRY physical mixture group， cmax， AUC0-24 h and AUC0-∞ were increased significantly in Co-amorphous CUR-TRY group （P＜0.01）； Relative bioavailability of CUR  was improved by 2.14 and 1.86 fold （P＜0.01）. CONCLUSIONS：Prepared Co-amorphous CUR-TRY can effectively improve in vitro dissolution and in vivo bioavailability in rats of CUR.

Analysis on mechanisms and medication rules of herbal prescriptions for nonalcoholic fatty liver disease based on methods of data mining and biological information / 中国中药杂志

To explore the medication rules of herbal prescriptions for nonalcoholic fatty liver disease,and analyze the possible drug targets and interactions,in order to explore the mechanisms of the herbs. Randomized controlled trials of herbal prescriptions for treating nonalcoholic fatty liver disease were collected from CNKI,Wan Fang,VIP,Sino Med and PubMed databases. The properties,flavors and meridian tropism of herbs were analyzed by using systematic cluster analysis method with SPSS 19. 0 software. Subsequently,the association rules of herbs were analyzed by using Clementine 12. 0 software. Finally,the interactions between targets and relevant signaling pathways were analyzed by Traditional Chinese Medicine Systems Pharmacology Database(TCMSP),Search Tool for the Retrieval of Interacting Genes/Proteins(STRING) and Kyoto Encyclopedia of Genes and Genomes(KEGG). In the 88 prescriptions screened out,the commonly used herbs were Salvia miltiorrhiza,Bupleurum chinense,Alisma orientale,and Crataegus pinnatifida,and the potential signaling pathways were PPAR signaling pathway and calcium signaling pathway. The results showed that the main effects of herbal prescriptions were to improve blood flow/clear blood stasis,clear heatiness/dampness,promote digestion and strengthen spleen. And its mechanism of action may be achieved through the regulation of PPAR signaling pathway and calcium signaling pathway.

Immunization of category B vaccine and its influencing factors among children aged 0 to 6 in Hangzhou / 预防医学

Objective To explore the immunization of category B vaccine and its influencing factors among children aged 0 to 6 in Hangzhou City. Method We carried out an investigation with 685 parents of children aged 0 to 6 from January to February in 2017 by using stratified random sampling method. Statistical method was used to analyze the knowledge, behaviors and attitudes towards category B vaccine, and logistic regression was applied to explore the determinant factors of category B vaccine behavior. Results 670 parents were under actual survey, 467 children have been vaccinated at least one kind of category B, which accounts for 69.70％ and the rates of five main types of vaccine were lower than 30％. Logistic regression showed that people of citizen (OR=1.54, 95％ CI: 1.14-2.38) , able to distinguish category A or B vaccine (OR=2.05, 95％ CI: 1.26-3.33) , positive attitude towards category B vaccine (OR=2.46, 95％CI: 1.43-4.23), and higher affordable price (OR=3.15, 95％CI:2.07-4.80) were determinant factors of category B vaccine behavior . Conclusion The rate of category B vaccine behavior of children aged 0 to 6 is on a moderate level. The cognition and attitude of children' s parents on category A vaccine and category B vaccine have effect on the immunization status of category B vaccine among children aged 0 to 6 in Hangzhou.

An investigation on lead, cadmium and methylmercury in seafood of Zhoushan City / 预防医学

Objective To analysis status of lead,cadmium and methylmercury residue in commercially available seafood during 2013-2015 in Zhoushan area.Methods During the period of 2013 to 2015,3 kinds of 1 134 seafood samples from representative farmer market in four districts of Zhoushan were collected to detect the lead,cadmium and methylmereury residue in seafish,mollusks and shellfish.Kruskal-Wallis rank-sum test were used to compare the difference of heavy metal residue in different years of seafood and exact propability were used to evaluate the difference of edible safety in different years.Results Of 1 134 seafood samples,the content of lead,cadmium and methylmereury was 0.011 5-0.555,0.0003-0.328,ND-0.302 mg/kg,respectively.The over-standard rate of lead in 2013 and 2015 were 0.79％ and 0.53％,found in five samples of seafish and shellfish,and the over-standard rate of cadmium in 2013 was 0.79％,found in three samples of seafish.Methylmercury residue in seafood wsa not found exceed the standard.Conclusion The contamination of lead,cadmium and methylmercury residue in commercially available seafood during 2013-2015 in Zhoushan area was in low level,but the content of lead and cadmium in seafood was over-standard.We should pay more attention to the lead content in shellfish,and lead and cadmium content in sea fish.

Clinical and genetic analyses of a family with atypical nonketotic hyperglycinemia caused by compound heterozygous mutations in the GLDC gene / 中国当代儿科杂志

Nonketotic hyperglycinemia (NKH) is an autosomal recessive hereditary disease caused by a defect in the glycine cleavage system and is classified into typical and atypical NKH. Atypical NKH has complex manifestations and is difficult to diagnose in clinical practice. This article reports a family of NKH. The parents had normal phenotypes, and the older brother and the younger sister developed this disease in the neonatal period. The older brother manifested as intractable epilepsy, severe spastic diplegia, intellectual disability, an increased level of glycine in blood and cerebrospinal fluid, an increased glycine/creatinine ratio in urine, and an increased ratio of glycine concentration in cerebrospinal fluid and blood. The younger sister manifested as delayed language development, ataxia, chorea, mental and behavior disorders induced by pyrexia, hypotonia, an increased level of glycine in cerebrospinal fluid, and an increased ratio of glycine concentration in cerebrospinal fluid and blood. High-throughput sequencing found a maternal missense mutation, c.3006C>G (p.C1002W), and a paternal nonsense mutation, c.1256C>G (p.S419X), in the GLDC gene in both patients. These two mutations were thought to be pathogenic mutations by a biological software. H293T cells transfected with these two mutants of the GLDC gene had a down-regulated activity of glycine decarboxylase. NKH has various phenotypes, and high-throughput sequencing helps to make a confirmed diagnosis. Atypical NKH is associated with the downregulated activity of glycine decarboxylase caused by gene mutations.

An analysis on metabolic indices among diabetic patients in different seasons / 预防医学

Objective To analysis the metabolic index among diabetic patients in community in summer and winter,and to provide evidence for disease management.Methods During June and December,119 diabetic patients were seleted from communities living for more than a year by the method of stratified cluster sampling.The metabolic indexes were compared usingpaired t test ,and the rate of biochemical indicators were analyzed by McNemar 's test between two seasons .Results The values of HbA1c,GLU and HDL -C were higher in winter than in summer (P <0.01).The mean values of TC in summer and winter were the same.The detection values of triglyceride and low density lipoprotein were lower in winter than in summer,but the difference was not statistically significant (P >0.05 ).The control rate of HbA1c was 56.36% in summer,and the control rate was 44.54% in winter,the difference was statistically significant (P <0.05).In summer, the control rate was 59.66%,higher than 45.38% in winter,and the difference was statistically significant (P <0.05). The control rate of blood pressure was better than that in winter,while triglyceride and low density lipoprotein control was better than that in summer,but which was not statistically significant (P >0.05).Conclusion The metabolic index of diabetic patients in Zhoushan urban community was significantly affected by seasonal changes.Most indexes were better in summer than that in winter,which suggested that the intervention of diabetics should be enhanced in winter.

The effects of gutter oil on liver function,renal function and serum lipid metabolism in mice / 预防医学

Objective To determine the effects of gutter oil on liver function,renal function and serum lipid metabolism in mice.Methods A total of 72 mice were averagely divided into 6 groups.Mice were gavaged with different dosages (5 μL/g,1 0 μL/g and 20 μL/g)of gutter oil or cooking oil every other day for continuing 8 weeks.The indexes of liver, kidney and serum lipid parameters were assayed.Results The moisture,acid value and peroxide value of the gutter oil exceeded the national standard.After continuing 8 weeks'intake of oils,alanine aminotransferase (ALT)of gutter oil group with a dosage of 5 μL/g,as well as aspartate aminotransferase (AST)of gutter oil group with a dosage of 1 0 μL/g significantly increased (P <0.05),compared with the cooking oil group.Serum creatinine (Scr)of the gutter oil groups with 3 dosages significantly increased compared with the control groups (P <0.05 ).Meanwhile,blood urea nitrogen (BUN)of gutter oil groups with a dosage of 5 μL/g and 1 0 μL/g were also significantly increased respectively(P <0.05). However,no significant differences were observed in triglyceride (TG)and total cholesterol (TC)among the groups. Conclusion Eight weeks'intake of gutter oil could cause the damage to liver and renal functions.

Epidemiological analysis of childhood cancer in China / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To analyze the epidemiological features of childhood cancer in China, and to provide some clues and basis for related academic research, the formulation of prevention and control strategy, and the construction of prevention and control system of childhood cancer.</p><p><b>METHODS</b>The data of childhood cancer in children aged 0-14 years which were published in Chinese Cancer Registry Annual Report in 2009-2012 and from GLOBOCAN2012 database were collected. A descriptive statistical analysis was done to determine the distributions of incidence and mortality by time, area, age, and sex.</p><p><b>RESULTS</b>In China, the incidence of childhood cancer showed a slight fluctuation with time, while the mortality rate remained stable. The incidence of childhood cancer in China was lower than the world average, and it was much lower than in the United States and Japan. However, the mortality of childhood cancer in China was higher than that in the United States and Japan. The incidence of childhood cancer in Chinese urban areas was about 2 times that in Chinese rural areas, while the mortality in the urban and rural areas was similar. The incidence and the mortality of childhood cancer both declined with increasing age. The incidence and the mortality of childhood cancer in boys were higher than those in girls.</p><p><b>CONCLUSIONS</b>The incidence and mortality of childhood cancer in China show distribution characteristics by time, area, age, and sex, which can help to make clear the future direction of childhood cancer research and provide some ideas for the comprehensive prevention and control.</p>

The Benefit Risk Assessment of Consumption of Marine Species Based on Benefit-Risk Analysis for Foods (BRAFO)-tiered Approach / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To assess the net health effect caused by the consumption of specific marine species based on Benefit-Risk Analysis for Foods (BRAFO)-tiered approach.</p><p><b>METHODS</b>Twenty species were collected from the Zhoushan Archipelago, China. Concentrations of n-3 long-chain polyunsaturated fatty acids, methyl mercury (MeHg), and dioxin-like compounds (DLCs) in the samples were analyzed for benefit risk assessment based on BRAFO-tiered approach.</p><p><b>RESULTS</b>Based on the BRAFO-tiered approach, reference scenario (no intake) and alternative scenario (intake of specific species of 200 g/week) were determined. The exposure to MeHg/DLCs via alternative scenario of all studied species did not exceed provisional tolerable weekly/monthly intake. However, the adult population with high DLCs exposure in China would significantly exceed the upper limit of DLCs via an additional alternative scenario of some species such as Auxis thazard. The results of deterministic computation showed that alternative scenario of all studied species generated clear net beneficial effects on death prevention and child IQ gain.</p><p><b>CONCLUSION</b>The alternative scenario of all studied species could be recommended to population with average DLCs exposure, and the reference scenario of species with relatively high DLCs concentration could be recommended to population exposed to high DLCs.</p>