34 medical college students and 26 patients with primary hypertension were served as the subjects on low sodium salt diet for 4 weeks. Before and after the experiment, serum and urinary sodium and potassium, as well as blood presure, pulse rate, and body weight were measured. During the testing period, calorie and protein were supplied sufficiently and the salt content in their common diet taken was restricted strictly. The results showed that the serum sodium decreased, potassium increased at the end of the experiment, but the changes were all within the physiological permissible limits. On the contrary, urinary sodium increased, potassium decreased and the Na/K dropped markedly, body weight increased slightly in healthy subjects and decreased by 1.0-3.0kg in patients with hypertension. The blood pressure, both systolic and diastolic, was decreased but no change in the pulse rate was observed.It was obvious that in the subjects on common salt diet, the body sodium was high and potassium low, otherwise on low sodium salt diet, such situation might be improved, and the high blood pressure could also be ameliorated in the type Ⅰ and Ⅱ of hypertension.

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.

Objective:To investigate the effects of three monomer components stilbene glycoside, emodin, catechin of Polygonum multiflorum on damages of liver tissue and cell.Methods:A total of 48 rats were randomly divided into four groups of stilbene glycoside, emodin, catechin-and normal saline(control)-treated groups(n=12, each). Rats were gavaged with the same dose of 1 g/kg for stilbene glycoside, emodin, catechin groups and normal saline for control group for 28 days.During the administration, the general state of rat was observed.After the last administration, serum biochemical indexes related to liver function were detected.Pathological morphological changes of liver tissue were observed by hatmatoxylin-Eosin(HE)staining.The expression levels of apoptosis-related proteins in liver tissue were determined by Western blot.Cells of human normal liver cell line LO2 divided into the stilbene glycoside-, emodin-, catechin-treated cells groups were cultured with 7 different concentrations of interfering agents for 24 h and 48 h respectively, and cultured with normal saline in the control group for the same time.Cell proliferation was observed using the cholecystokinin octapeptide(CCK8), and the mRNA expressions of apoptosis-related factors were detected using PCR.Results:After 28 days of feeding, there was no significant difference in body weight and food intake among the four groups( P>0.05). Pathological liver damage and abnormal liver biochemical indexes were observed in rat liver tissues in the emodin and catechin groups( P<0.05). Compared with the control group, the expression levels of anti-apoptotic proteins Bcl-2 were decreased(0.34±0.03, 0.41±0.07 vs.0.45±0.04, P<0.05), the expression levels of apoptotic proteins Caspase-3 and Bax were increased(0.76±0.03, 0.27±0.06 vs.0.03±0.00; 0.44±0.03, 0.15±0.04 vs.0.02±0.00, P<0.01), and those in the stilbene glycoside group were normal.Compared with the control group, emodin and catechin-treated cell groups showed the concentration-and time-dependent proliferation inhibition in LO2 normal hepatocytes( P<0.05)after treatment.And the mRNA expression of hepatocyte apoptosis factors Bax and Caspase-3 were increased(1.74±0.05, 1.29±0.01 vs.0.89±0.12, 1.21±0.07, 1.25±0.01 vs.0.97±0.07, P<0.01), and that of anti-apoptotic proteins Bcl-2 was decreased(0.06±0.06, 0.56±0.11 vs.1.39±0.18, P<0.01). Compared with the control group, the survival rate had no significant difference in the stilbene glycoside treated-cell group( P>0.05), while its mRNA expression of hepatocyte apoptosis factors was reduced( P<0.05). Conclusions:No obvious liver damage is found in rats treated with the stilbene glycoside of Polygonum multiflorum, but the emodin and catechin cause damages of liver tissue and cell in vivo and in vitro.

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 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 relationship between different tidal volume (VT) mechanical ventilation (MV) and autophagy and mitochondrial damage in rats. METHODS: A total of 120 clean-grade male Sprague-Dawley (SD) rats were divided into five groups (n = 24) by random number table method, and then given 0 (spontaneous breathing), 10, 20, 30, 40 mL/kg VT for MV. The rats in each group were subdivided into four subgroups of 1, 2, 3, and 4 hours according to ventilation time, with 6 rats in each subgroup. The lung tissue and bronchoalveolar lavage fluid (BALF) were harvested, and alveolar macrophages (AMs) and type II alveolar epithelial cells (AEC II) were cultured in vitro. The mRNA and protein expressions of autophagy-associated protein microtubule-associated protein 1 light chain 3B-II (LC3B-II) and autophagy-related genes Beclin1 and p62 were determined by reverse transcription-polymerase chain reaction (RT-PCR) or Western Blot. Lung autophagosome formation was observed under transmission electron microscope. The levels of adenosine triphosphate (ATP), reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) in lung tissue were determined for assessing mitochondrial damage. RESULTS: There were no significant differences in the mRNA and protein expressions of LC3B-II, p62 and Beclin1 at 1 hour after ventilation among the groups. With the prolonged ventilation time, the mRNA and protein expressions of LC3B-II, p62 and Beclin1 in MV groups were increased gradually, peaked at 2-3 hours, and they were increased significantly in 30 mL/kg VT group as compared with those in spontaneous respiration group with statistical significances [ventilation for 2 hours: LC3B-II mRNA (2^-ΔΔCt) was 2.44±0.24 vs. 1.12±0.04, LC3B-II/LC3B-I was 1.42±0.16 vs. 0.57±0.03, p62 mRNA (2^-ΔΔCt) was 2.96±0.14 vs. 1.14±0.02, Beclin1 mRNA (2^-ΔΔCt) was 2.80±0.13 vs. 1.14±0.02; ventilation for 3 hours: p62/β-actin was 1.14±0.15 vs. 0.55±0.04, Beclin1/β-actin was 1.27±0.06 vs. 0.87±0.04, all P < 0.05]. Autophagosomes and autolysosomes were found in AEC II after ventilation for 2 hours at 30 mL/kg VT by transmission electron microscopy, but not in AEC I. Compared with spontaneous breathing group, ATP synthesis in AMs was significantly decreased at 2 hours of ventilation in 30 mL/kg VT group (A value: 0.82±0.05 vs. 1.00±0.00, P < 0.05), ROS accumulate in AMs and AEC II were significantly increased [ROS in AMs: (33.83±4.00)% vs. (6.90±0.62)%, ROS in AEC II: (80.68±0.90)% vs. (2.16±0.19)%, both P < 0.05]. With the increase in VT and the prolongation of ventilation time, ATP and ROS levels in AMs and AEC II were gradually decreased, the ATP (A value) in AMs at 4 hours of ventilation in 40 mL/kg VT group was 0.41±0.05, the ROS in AMs was (12.95±0.88)%, and the ROS in AEC II was (40.43±2.29)%. With the increase in VT and the prolongation of ventilation time, MMP levels were gradually increased, the MMP (green/red fluorescence intensity ratio) in AMs at 2 hours of ventilation in 30 mL/kg VT group was 1.11±0.17, the MMP in AEC II was 0.96±0.04, and the MMP (green/red fluorescence intensity ratio) at 4 hours of ventilation in 40 mL/kg VT group was 0.51±0.07 and 0.49±0.06, respectively. CONCLUSIONS The MV with high VT could induce autophagy activation and mitochondrial damage in lung tissue of rats, and the longer the ventilation time, the more obvious autophagy in the lung.
Animals ; Autophagy/physiology* ; Male ; Mitochondria/pathology* ; Rats ; Rats, Sprague-Dawley ; Respiration, Artificial/adverse effects* ; Tidal Volume ; Time Factors ; Ventilator-Induced Lung Injury

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 investigate the predictive value of ¹⁸F-FDG PET-CT scan for occult lymph node metastasis in patients with stage ⅠA 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 (SUV_max) 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 SUV_max (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 SUV_max=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 SUV_max >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 SUV_max > 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 SUV_max ≤ 2.405, due to the very low probability of nodal involvement.

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.