Objective To investigate the efficacy and safety of isosorbide mononitrate sustained release tables plus vinorelbine and cisplatin in patients with previously untreated advanced non-small-cell lung cancer (NSCLC).Methods One hundred and ten patients with stage ⅢB-Ⅳ NSCLC were randomly assigned to group A (57 cases) and group B (53 cases) by random mumber table.Patients in group A were treated with vinorelbine 25 mg/m2 on the first and eighth day and cisplatin 25 mg/m2 on day 2-4,with transdermally applied isosorbide mononitrate sustained release tables (40 mg,daily for 8 days),and patients in group B were treated with vinorelbine and cisplatin.Response to treatment was assessed by RECIST1.1 and adverse effect was assessed by NCI-CTC(3.0).Results The response rate in group A (58.2％,32/55 patients) was significandy higher than that for patients in group B (30.8％,16/52 patients; x2 =8.120,P =0.004).Median TTP and median OS in group A were longer than those in group B (8.2 vs 5.8 months,x2 =10.684,P =0.001 ; 11.6 vs 9.0 months,x2 =11.231,P =0.001).While,patients with squamous carcinoma showed better response to chemotherapy (RR =2.438,95％ CI:1.136-5.231,P =0.022).Adverse effect difference was not significant between group A and group B,except headache.The rate of grade 1 to 2 headache in group A (34.5％ ; 19 of 55 patients) was significantly higher than that in group B (3.8％ ; 2 of 52 patients; P ＜0.001).Conclusion Use of isosorbide mononitrate sustained release tables combined with vinorelbine and cisplatin may improve overall response,TTP and OS in patients with advanced stage NSCLC.

Objective To analyze the survival curves of ASIC3 -/-and TRPV1 -/-mice, and provide a reference for further breeding of these strains of mice.Methods Forty-four ASIC3 -/-mice and sixty-one TRPV1 -/-mice were included in this study.The survival of the mice was observed in normal feeding for 500 days, survival curves were drawn, and their survival was analyzed.Results With the passing of time, the survival probability was decreased in ASIC3 -/-mice and TRPV1 -/-mice.The survival probability of TRPV1 -/-mice was significantly better than that of ASIC3 -/-mice (P =0.004, P <0.01).No significant difference was observed between the males and females of the same strain. Conclusions The survival probability of TRPV1 -/-mice is better than that of ASIC3 -/-mice.There is no significant gender difference in the two strains of mice.

Reactive oxygen species play a crucial role in maintaining metabolic balance in the body. They are not only important mediators in maintaining a normal physiological environment, but also important triggers for the occurrence and development of many diseases. Osteoarthritis is the most common degenerative joint disease at present. Due to the aging population, extended life expectancy and obesity, the incidence rate and prevalence of osteoarthritis have increased year by year. Recent studies on osteoarthritis show that reactive oxygen species play a crucial role in its occurrence and development, and are key factors leading to extracellular matrix degradation, mitochondrial dysfunction, chondrocyte apoptosis and the progress of osteoarthritis. For osteoarthritis, moderate levels of reactive oxygen species can promote the proliferation of chondrocytes and the formation of cartilage matrix. However, excessive accumulation of reactive oxygen species can induce oxidative stress, leading to degeneration of chondrocytes and breakdown of cartilage matrix, ultimately resulting in the occurrence of osteoarthritis and many other metabolic diseases. In recent years, hydrogels have attracted attention as new biomaterials for the treatment of osteoarthritis. Reactive oxygen scavenging hydrogels are a new type of polymer biomaterials with drug intelligent delivery function that can regulate tissue oxidative stress and inflammatory reaction. They mainly include traditional reactive oxygen scavenging hydrogels with the main function of loading reactive oxygen scavenging drugs and reactive oxygen responsive hydrogels with reactive oxygen responsive groups. The former mainly uses slow-release drugs with reactive oxygen species scavenging properties encapsulated in it to treat osteoarthritis, while the latter can not only clear the reactive oxygen species generated during the occurrence and development of osteoarthritis by breaking the reactive oxygen species responsive groups, but also responsively deliver various drugs for treating osteoarthritis. Reactive oxygen scavenging hydrogels have a good prospect in the treatment of osteoarthritis and repair.

OBJECTIVE: To explore the genetic basis for a family with non-syndromic autosomal recessive deafness. METHODS: The proband and her parents were subjected to physical and audiological examinations. With genomic DNA extracted from peripheral blood samples, next-generation sequencing was carried out using a panel for deafness genes. Suspected mutation was validated by Sanger sequencing and qPCR analysis of her parents. RESULTS: The proband presented bilateral severe sensorineural hearing loss at three days after birth. Her auditory threshold was 110-120 dBnHL but with absence of vestibular and retinal symptoms. Her brother also had deafness but her parents were normal. No abnormality was found upon physical examination of her family members, while audiological examination showed no middle ear or retrocochlear diseases. Next-generation sequencing identified compound heterozygous mutations of the MYO7A gene, including a previously known c.462C>A (p. Cys154Ter) and a novel EX43_46 Del, which were respectively derived from her mother and father. CONCLUSION The compound heterozygous mutations of the MYO7A gene probably underlie the disease in this family. Our findings has enriched the mutation spectrum for non-syndromic autosomal recessive deafness 2.
Female ; Hearing Loss, Sensorineural ; genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Mutation ; Myosins ; genetics ; Pedigree

Objective To investigate the predictive value of neutrophil to lymphocyte ratio (NLR) in peripheral blood for the outcomes in patients with acute intracerebral hemorrhage.Methods Consecutive inpatients with intracerebral hemorrhage diagnosed with the head CT were entolled.The modified Rankin Scale (mRS) was used to evaluate the functional outcomes at 90 d,0-2 wvas defined as good outcome,3-6 were defined as poor outcome,and 6 was defined as death.Univariate analysis was used to compare the demographic characteristics,baseline data,imaging,and laboratory findings between the groups.Multivariate logistic regression analysis was used to determine the independent correlation between NLR and the outcomes,and receiver operating characteristics (ROC) analysis was performed to assess the predictive value of NLR for the outcomes.Results A total of 205 patients with acute intracerebral hemorrhage were enrolled in the study,107 (52.2％) had poor outcome and 57 (27.8％) died.There were significant differences in age (P=0.038),Glasgow Coma Scale (GCS) scores (P=0.001),National Institutes of Health Stroke Scale (NIHSS) scores (P =0.001),neutrophil count (P =0.005),lymphocyte count (P =0.002),NLR (P =0.001),fasting blood glucose (P =0.012),hypersensitivity C-reactive protein (P=0.002),hematoma volume (P =0.005),and proportion of bleeding into the ventricles (P =0.002) between the poor outcome group and the good outcome group.There were significant differences in age (P =0.002),previous stroke (P =0.018),GCS scores (P =0.001),NIHSS scores (P =0.001),neutrophil count (P=0.008),lymphocyte count (P=0.001),NLR (P=0.001),fasting blood glucose (P=0.016),hematoma volume (P=0.001),and proportion of bleeding into ventricle (P=0.002) between the death group and the survival group.Multivariate logistic regression analysis showed that NLR was an independent predictive factor for poor outcome (odds ratio [OR] 2.405,95％ confidence interval [CI] 1.613-3.587;P=0.001) and death (OR 2.268,95％ CI 1.532-3.358;P =0.001) after adjusting for confounders.The ROC curve analysis showed that NLR had a higher predictive value for poor outcome at 90 d (area under the ROC curve 0.703,95％ CI 0.632-0.774;P ＜ 0.001).When the cutoff value was 2.3,the sensitivity and specificity were 61.7％ and 72.4％,respectively.NLR also had a predictive value for death within 90 d (area under the ROC curve 0.706,95％ CI 0.629-0.786;P =0.003).When the cutoff value was 2.2,the sensitivity and specificity were 63.2％ and 72.6％,respectively.Conclusion NLR may have certain predict value for outcomes in patients with acute intracerebral hemorrhage.

Objective To investigate the predictive value of 18F?FDG PET?CT scan for occult lymph node metastasis in patients with stageⅠA lung adenocarcinoma. Methods The image and pathological data of 272 patients with stage ⅠA lung adenocarcinoma from October 2006 to September 2015 were retrospectively analyzed. All patients underwent preoperative 18F?FDG PET?CT scan followed by lobectomy and systematic lymph node dissection. The correlation between occult lymph node metastasis and the maximum standardized uptake value (SUVmax) of primary tumor as well as other clinicopathological factors was analyzed to screen the risk factors of occult lymph node metastasis in stage ⅠA lung adenocarcinoma. Results Occult lymph node metastasis was detected in 50 patients (18.4%), with 24 (8.8%) patients of pN1 involvement and 26 (9.6%) of pN2 involvement. Among the 272 patients enrolled, 39 had pure ground glass nodule, 59 had part?solid nodule and 174 had solid nodule. All patients with pure ground glass nodule or nodule≤1 cm were pN0. For the 233 patients with part?solid and solid nodule, no lymph node metastasis was found in T1a stage (tumor length≤1 cm). Primary tumor SUVmax(Z＝－5.663, P＜0.001), nodule type (χ2＝21.586, P＜0.001), tumor location (χ2＝ 12.790, P＜ 0.001), histological grade ( χ2＝ 22.784, P＜0.001) and visceral pleural invasion (χ2＝5.357, P＝0.021) showed significant differences between occult lymph node metastasis group (pN+) and non?lymph node metastasis group (pN0). With SUVmax＝2.405 as cut?off value, the sensitivity and specificity for predicting occult lymph node metastasis were 90.0% and 61.7%, the area under curve was 0.761(95%CI＝0.700～0.823), and the negative predictive value was 95.8%. Multivariate analysis revealed that SUVmax＞2.405 (P＜0.001), central location ( P＝0.030) and higher histological grade ( P ＝ 0.024 ) were independent predictors of occult lymph node metastasis. Conclusions For clinical stage ⅠA adenocarcinoma, primary tumor SUVmax＞ 2.405, central location and higher histological grade were independent risk factors for occult lymph node metastasis. Systematic lymph node dissection may be avoided in lung adenocarcinoma with pure ground glass density, tumor length≤1 cm or SUVmax≤2.405, due to the very low probability of nodal involvement.

Objective To investigate the predictive value of 18F?FDG PET?CT scan for occult lymph node metastasis in patients with stageⅠA lung adenocarcinoma. Methods The image and pathological data of 272 patients with stage ⅠA lung adenocarcinoma from October 2006 to September 2015 were retrospectively analyzed. All patients underwent preoperative 18F?FDG PET?CT scan followed by lobectomy and systematic lymph node dissection. The correlation between occult lymph node metastasis and the maximum standardized uptake value (SUVmax) of primary tumor as well as other clinicopathological factors was analyzed to screen the risk factors of occult lymph node metastasis in stage ⅠA lung adenocarcinoma. Results Occult lymph node metastasis was detected in 50 patients (18.4%), with 24 (8.8%) patients of pN1 involvement and 26 (9.6%) of pN2 involvement. Among the 272 patients enrolled, 39 had pure ground glass nodule, 59 had part?solid nodule and 174 had solid nodule. All patients with pure ground glass nodule or nodule≤1 cm were pN0. For the 233 patients with part?solid and solid nodule, no lymph node metastasis was found in T1a stage (tumor length≤1 cm). Primary tumor SUVmax(Z＝－5.663, P＜0.001), nodule type (χ2＝21.586, P＜0.001), tumor location (χ2＝ 12.790, P＜ 0.001), histological grade ( χ2＝ 22.784, P＜0.001) and visceral pleural invasion (χ2＝5.357, P＝0.021) showed significant differences between occult lymph node metastasis group (pN+) and non?lymph node metastasis group (pN0). With SUVmax＝2.405 as cut?off value, the sensitivity and specificity for predicting occult lymph node metastasis were 90.0% and 61.7%, the area under curve was 0.761(95%CI＝0.700～0.823), and the negative predictive value was 95.8%. Multivariate analysis revealed that SUVmax＞2.405 (P＜0.001), central location ( P＝0.030) and higher histological grade ( P ＝ 0.024 ) were independent predictors of occult lymph node metastasis. Conclusions For clinical stage ⅠA adenocarcinoma, primary tumor SUVmax＞ 2.405, central location and higher histological grade were independent risk factors for occult lymph node metastasis. Systematic lymph node dissection may be avoided in lung adenocarcinoma with pure ground glass density, tumor length≤1 cm or SUVmax≤2.405, due to the very low probability of nodal involvement.

ObjectiveTo observe the effects of electroacupuncture at Zhongwan （CV12） on gastric nociceptive response induced by gastric acid stimulation and explore the underlying mechanisms associated with nuclei of the medullary viscerosensory and visceral motor neurons. MethodsTwenty SD rats were given intragastric administration of 0.5 mol/L diluted hydrochloric acid （0.5 ml/100 g） to induce gastric nociceptive response induction. Eight rats were randomly selected to record the gastric slow wave （GSW） area under the curve， and extracellular discharge frequency of neurons in the nucleus of the solitary tract （NTS） and dorsal motor nucleus of the vagus nerve （DMV） before intragastric administration and at 1， 5， 10， 15， 20， 25， 30， 35， 40， 45， 50， 55， and 60 minutes after intragastric administration. The remaining 12 rats received electroacupuncture intervention at Zhongwan within 5 to 25 minutes after intragastric administration of diluted hydrochloric acid， with a duration of one minute. The GSW area under the curve and extracellular discharge frequency of NTS and DMV neurons were compared between the 1-minute intervals before and after electroacupuncture intervention. ResultsCompared to the baseline before intragastric administration， the area under the curve of GSW significantly increased at 1， 5， 10， 15， 20， and 25 minutes after intragastric administration， and the extracellular discharge frequency of excitatory neurons in the NTS （accounting for 90%， 57/63） significantly increased at 1， 5， 10， 15， 20， 25， 30， 35， and 40 minutes， both reaching peak values at 1 minute after intragastric administration （P＜0.01 or P＜0.05）. The extracellular discharge frequency of inhibitory neurons in the DMV （accounting for 91%， 20/22） showed a non-significant increase at 1 minute after intragastric administration （P＞0.05）， but significantly decreased at other timepoints （P＜0.05）. Compared to the baseline before electroacupuncture intervention， the GSW area under the curve and the extracellular discharge frequency of excitatory neurons in the NTS significantly decreased （P＜0.05）， while the extracellular discharge frequency of inhibitory neurons in the DMV showed no significant difference （P＞0.05）. ConclusionElectroacupuncture at Zhongwan can improve gastric nociceptive response induced by gastric acid stimulation， possibly by reducing the transmission of visceral sensation and decreasing the excitability of NTS neurons in the medulla.

Objective: To explore the genetic basis for a family with non-syndromic autosomal recessive deafness. Methods: The proband and her parents were subjected to physical and audiological examinations. With genomic DNA extracted from peripheral blood samples, next-generation sequencing was carried out using a panel for deafness genes. Suspected mutation was validated by Sanger sequencing and qPCR analysis of her parents. Results: The proband presented bilateral severe sensorineural hearing loss at three days after birth. Her auditory threshold was 110-120 dBnHL but with absence of vestibular and retinal symptoms. Her brother also had deafness but her parents were normal. No abnormality was found upon physical examination of her family members, while audiological examination showed no middle ear or retrocochlear diseases. Next-generation sequencing identified compound heterozygous mutations of the MYO7A gene, including a previously known c. 462C>A (p. Cys154Ter) and a novel EX43_46 Del, which were respectively derived from her mother and father. Conclusion The compound heterozygous mutations of the MYO7A gene probably underlie the disease in this family. Our findings has enriched the mutation spectrum for non-syndromic autosomal recessive deafness 2.

Background Essential and non-essential elements have an important impact on the development of the central nervous system during fetal development. Due to their less developed brain, preterm infants are more sensitive to element exposure, and are high-risk groups of neurodevelopmental abnormalities. However, it is not clear whether the effects of element exposure in utero on postpartum neurodevelopment are different between full-term infants and preterm infants. Objective To evaluate the effects of element exposure levels during pregnancy on neurodevelopment of children aged 6-24 months (of corrected age), and compare the effects between preterm and full-term children. Methods A prospective study design was adopted and this study was conducted based on the Maoming Birth Cohort Study (MBCS) in Maoming City, Guangdong Province. Twenty elements in cord blood of 197 preterm infants and 297 full-term infants were measured, including 11 essential trace elements [vanadium (V), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), selenium (Se), strontium (Sr), tin (Sn), and iron (Fe)], and 9 non-essential trace elements [aluminum (Al), arsenic (As), thallium (Tl), lead (Pb), uranium (U), cerium (Ce), antimony (Sb), cadmium (Cd), and yttrium (Y)]. The neurodevelopment of the children at 6, 12, and 24 months were evaluated by the Ages and Stages Questionnaires-the Third Edition (ASQ-3). A generalized estimating equation (GEE) model was adopted to evaluate the associations between elements and neurodevelopment in full-term and preterm children separately. Results The positive rates of 10 elements (Mn, Cu, Zn, Se, Sr, Fe, Sb, Tl, Pb, and As) in cord blood were greater than 80%. Among the preterm birth children, the results of GEE analysis showed that after adjusting for the covariates, for each increase of interquartile range (IQR) in ln-transformed concentration, As was associated with problems/delay in the communication and problem-solving sub-scales, with the adjusted odds ratios (OR) and 95% confidence intervals (CI) of 1.36 (1.03-1.80) and 1.55 (1.10-2.20), respectively; the adjusted OR (95%CI) of problems/delay in the fine motor and problem-solving sub-scales were 1.44 (1.00-2.07) and 1.76 (1.09-2.84) for Sb, respectively; the adjusted OR (95%CI) of problems/delay in the communication sub-scale was 1.37 (1.09-1.74) for Se. No statistically significant associations between umbilical cord blood element concentrations and neurodevelopment indicators were observed among full-term children. The results of stratified analysis by sex showed that the associations between umbilical cord blood element concentrations and neurodevelopment problems/delay were only significant among female preterm children. Conclusion Exposures to As, Se, and Sb during pregnancy may increase the risk of neurodevelopment problems/delay in preterm children aged 6-24 months, and female seem to be more vulnerable.