1.THE STUDY OF LOW SODIUM SALT DIET
Wenli TANG ; Zhaokun JIANG ; Yuguang LIN ; Zhiying ZHANG ; Xiaoyan ZHU
Acta Nutrimenta Sinica 1956;0(01):-
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.
2.Clinical investigation of isosorbide mononitrate plus vinorelbine and cisplatin in patients with previously untreated advanced non-small cell lung cancer
Zhaokun ZHONG ; Ping WANG ; Yao ZHANG ; Weijun CHEN ; Ze YU ; Lei LIU ; Dongmei ZHOU
Journal of International Oncology 2013;40(8):625-629
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.
3.Survival analysis of ASIC3 -/-and TRPV1 -/-mice
Hong SHI ; Wei HE ; Xiaoyu WANG ; Ling HU ; Yangshuai SU ; Juanjuan XIN ; Zhaokun YANG ; Xu HAN ; Jie GAO ; Yi ZHANG ; Xianghong JING
Chinese Journal of Comparative Medicine 2014;(10):78-81,89
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.
4.The study of monomer components of Polygonum multiflorum on liver tissue and cell damages
Xueqi HONG ; Yi ZHANG ; Huijun DAI ; Zhaokun HU ; Linghui PAN
Chinese Journal of Geriatrics 2020;39(7):834-839
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.
5.Research progress of reactive oxygen scavenging hydrogel in osteoarthritis
Pengfei HUANG ; Junjie ZHAO ; Zhaokun ZHANG ; Xiyu WANG ; Yuhao ZHAO ; Haiyan ZHAO
Chinese Journal of Orthopaedics 2024;44(17):1184-1190
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.
6.Neutrophil to lymphocyte ratio predicts the outcomes in patients with acute intracerebral hemorrhage
Yun ZHANG ; Xinying FAN ; Shunyuan ZHANG ; Qian LUO ; Jinqiu WANG ; Mingjun PU ; Jiacai ZUO ; Zhaokun LI ; Jinfeng DUAN
International Journal of Cerebrovascular Diseases 2017;25(7):638-643
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.
7.Analysis of MYO7A gene mutation in a family with non-syndromic autosomal recessive deafness.
Shengran WANG ; Litao QIN ; Keyue DING ; Bingtao HAO ; Shasha BIAN ; Zhaokun WANG ; Qingqing WANG ; Xin WANG ; Weihua ZHANG ; Shixiu LIAO
Chinese Journal of Medical Genetics 2019;36(10):965-969
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
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Hearing Loss, Sensorineural
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genetics
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High-Throughput Nucleotide Sequencing
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Humans
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Male
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Mutation
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Myosins
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genetics
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Pedigree
8.Effect of high tidal volume mechanical ventilation on pulmonary autophagy and mitochondrial damage in rats.
Zhaokun HU ; Ren JING ; Huijun DAI ; Suisui ZHANG ; Linghui PAN
Chinese Critical Care Medicine 2019;31(3):325-330
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
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Respiration, Artificial/adverse effects*
;
Tidal Volume
;
Time Factors
;
Ventilator-Induced Lung Injury
9.Potential value of FDG PET?CT in predicting occult lymph node metastasis in clinical stageⅠA lung adenocarcinoma
Lyu LYU ; Ying LIU ; Xiaoyi WANG ; Zhaokun ZHANG ; Xiuli TAO ; Lin YANG ; Ning WU
Chinese Journal of Oncology 2019;41(6):441-447
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.
10.Potential value of FDG PET?CT in predicting occult lymph node metastasis in clinical stageⅠA lung adenocarcinoma
Lyu LYU ; Ying LIU ; Xiaoyi WANG ; Zhaokun ZHANG ; Xiuli TAO ; Lin YANG ; Ning WU
Chinese Journal of Oncology 2019;41(6):441-447
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.