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.

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.

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.

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 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.

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

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.