Objective:To investigate the clinical efficacy of laparoscopic hiatal hernia repair with tunneled esophagogastric fundoplication and diaphragmatic dome suspension-fixation (HHR-TEF-DDSF) in the treatment of gastroesophageal reflux disease.Methods:The retrospective and descriptive study was conducted. The clinical data of 32 patients with gastroesophageal reflux disease who were admitted to Yifu Hospital Affiliated to Nanjing Medical University from October 2024 to June 2025 were collected. There were 20 males and 12 females, aged (68±7)years. All patients underwent laparoscopic HHR-TEF-DDSF. Observation indicators: (1) surgical and intraoperative conditions; (2) postoperative conditions; (3) follow-up. Measurement data with normal distribution were expre-ssed as Mean± SD, while measurement data with skewed distribution were expressed as M( Q1, Q3) or M(range). Count data were expressed as absolute numbers or percentages. Results:(1) Surgical and intraoperative conditions. All 32 patients successfully underwent laparoscopic HHR-TEF-DDSF. The operation time was (75±10)minutes, and volume of intraoperative blood loss was 50(50,100)mL. Among the 32 patients, there was no conversion to open surgery, no blood transfusion, no intra-operative complications such as unexpected massive hemorrhage or adjacent organ injury, no intra-operative adverse event or death. (2) Postoperative conditions. For the 32 patients, the time to post-operative first flatus was 1(1,2)days, the time to postoperative first defecation was 1(1,3)days, the time to postoperative first intake of liquid food was 1(1,3)days, the duration of postoperative drainage tube indwelling was 3(3,6)days, the postoperative hospital stay was 6(5,14)days, and the time to relief of postoperative dysphagia was 5(5,8)days. No obvious hiccup was observed in any patient in the short term after surgery. (3) Follow-up. All 32 patients were followed up for 7.5(range, 3.0-11.0)months. Among the 32 patients, 26 cases achieved subjective relief of overall postoperative digestive tract symptoms, and 32 cases achieved subjective relief of overall postoperative respiratory tract symptoms. The proton pump inhibitor (PPI) withdrawal rate was 84.4%(27/32), and the treatment satisfaction rate was 87.5%(28/32). The incidences of postoperative complications inclu-ding abdominal distension, dysphagia, diarrhea, and increased flatus were 21.9%(7/32), 18.8%(6/32), 6.3%(2/32), and 3.1%(1/32), respectively. Dysphagia was significantly relieved in all affected patients within 2 months after surgery, and no patient had persistent dysphagia by the end of the follow-up period. There was no death, symptom recurrence, or reoperation.Conclusion:HHR-TEF-DDSF is safe and feasible in the treatment of gastroesophageal reflux disease, with favorable short-term efficacy.

Objective To investigate the influencing factors associated with early neurological deterioration(END)in patients with minor acute ischemic stroke(mAIS),develop a clinical prediction model for END,and identify independent risk factors for 90-day neurological functional outcomes after stroke.Methods mAIS patients admitted consecutively to the Department of Neurology,Yijishan Hospital of Wannan Medical College(the First Affiliated Hospital of Wannan Medical College),from July 2023 to July 2024 were retrospectively collected.A minor ischemic stroke was defined as acute ischemic stroke with a National Institutes of Health stroke scale(NIHSS)score≤5 on admission.Baseline,clinical,and imaging data of all mAIS patients were collected and recorded,including demographic information(age,sex),past medical history(hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease,atrial fibrillation),smoking history,alcohol consumption,baseline blood pressure,pre-onset modified Rankin scale(mRS),NIHSS scores at admission and during hospitalization(24 hours,48 hours,72 hours after admission),motor component subscore of the NIHSS scores,NIHSS scores at discharge,trial of Org 10172 in acute stroke treatment(TOAST)classification,laboratory indicators(fasting blood glucose,hemoglobin A1c[HbA1c],total cholesterol,triglycerides,high-density lipoprotein,low-density lipoprotein),clinical treatment information(intravenous thrombolysis,mono antiplatelet therapy,dual antiplatelet therapy,anticoagulation therapy)and length of stay.The status of stenosis and occlusion in the culprit vessel were assessed based on imaging results.Mild-to-moderate stenosis was defined as a stenosis rate of 0％to 69％,severe stenosis as a stenosis rate of 70％to 99％,and occlusion as complete interruption of the supplying artery.END was defined as an increase in NIHSS score of ≥2 points from baseline within 72 hours after admission,combined with an increase of at least 1 point in the motor score compared to the score at admission.Prognosis was assessed via telephone follow-ups at 90-day after onset using mRS score,with an mRS score ≤ 2 indicating a favorable outcome and an mRS score＞2 indicating a poor outcome.Variables with P＜0.05 in the univariate analysis were incorporated into multivariate Logistic regression analysis to identify the independent risk factors for END in mAIS patients.A nomogram model was constructed,and calibration curves along with decision curve analysis were plotted to evaluate the model's goodness-of-fit and clinical utility.Univariate and multivariate Logistic regression analyses were performed to identify factors associated with poor 90-day functional outcome after mAIS.Results(1)A total of 826 patients were included,aged 33-94 years,with a median age of 67(57,76)years.There were 571 males and 255 females.The NIHSS score at admission ranged from 0 to 5,with a median NIHSS score at admission of 3(2,4).The NIHSS motor subscore at admission ranged from 0 to 5,with a median baseline NIHSS motor score of 2(0,2).Among them,119 patients(14.4％)were in the END group and 707 patients(85.6％)were included in the non-END group.At 90days after stroke,744 patients(90.1％)had a favorable outcome,while 82 patients(9.9％)had a poor outcome.(2)Univariate analysis showed that there were statistically significant differences between the END group and the non-END group in terms of HbA1c,fasting blood glucose,baseline NIHSS score,baseline NIHSS motor subscore,history of alcohol consumption,diabetes mellitus,culprit vessel stenosis and occlusion,and TOAST classification(all P＜0.05).Statistically significant differences were observed between the favorable outcome group and the poor outcome group in HbA1c,fasting blood glucose,incidence of END,baseline NIHSS score,discharge NIHSS score,culprit vessel stenosis and occlusion,TOAST classification,and history of alcohol consumption(all P＜0.05).(3)Multivariate Logistic regression analysis indicated that mAIS patients with severe stenosis of the culprit vessel(OR,5.88,95％CI2.32-14.91,P＜0.01),occlusion of the culprit vessel(OR,5.74,95％CI 2.25-14.62,P＜0.01),history of alcohol consumption(OR,5.59,95％CI3.41-9.17,P＜0.01),elevated HbA1c(OR,1.67,95％CI 1.35-2.08,P＜0.01),and higher baseline NIHSS motor score(OR,1.43,95％CI 1.08-1.89,P=0.012)had an increased risk of END.A higher discharge NIHSS score(OR,2.59,95％CI 1.89-3.57,P＜0.01)and the occurrence of END(OR,18.42,95％CI 5.13-66.18,P＜0.01)were associated with poor 90-day functional outcome after mAIS.(4)The nomogram model constructed based on independent risk factors of END in mAIS patients demonstrated an AUC of 0.78(95％CI 0.73-0.83)for predicting END,with a sensitivity of 0.8 and a specificity of 0.7.The model showed good calibration,and the Hosmer-Lemeshow test indicated good agreement between predicted and observed values(P=0.333).Decision curve analysis revealed that the model provided a high net benefit across a range of high-risk thresholds(0.1-0.7),suggesting its potential clinical utility.Conclusions Severe stenosis of the culprit vessel,occlusion of the culprit vessel,glycated hemoglobin levels,baseline NIHSS motor subscale scores,and history of alcohol consumption are independent risk factors for END in patients with mAIS.The nomogram model constructed based on these factors demonstrated good predictive performance.END and NIHSS scores at discharge are independent predictors of poor 90-day outcomes in patients with mAIS.

Objective:To investigate the clinical efficacy of laparoscopic hiatal hernia repair with tunneled esophagogastric fundoplication and diaphragmatic dome suspension-fixation (HHR-TEF-DDSF) in the treatment of gastroesophageal reflux disease.Methods:The retrospective and descriptive study was conducted. The clinical data of 32 patients with gastroesophageal reflux disease who were admitted to Yifu Hospital Affiliated to Nanjing Medical University from October 2024 to June 2025 were collected. There were 20 males and 12 females, aged (68±7)years. All patients underwent laparoscopic HHR-TEF-DDSF. Observation indicators: (1) surgical and intraoperative conditions; (2) postoperative conditions; (3) follow-up. Measurement data with normal distribution were expre-ssed as Mean± SD, while measurement data with skewed distribution were expressed as M( Q1, Q3) or M(range). Count data were expressed as absolute numbers or percentages. Results:(1) Surgical and intraoperative conditions. All 32 patients successfully underwent laparoscopic HHR-TEF-DDSF. The operation time was (75±10)minutes, and volume of intraoperative blood loss was 50(50,100)mL. Among the 32 patients, there was no conversion to open surgery, no blood transfusion, no intra-operative complications such as unexpected massive hemorrhage or adjacent organ injury, no intra-operative adverse event or death. (2) Postoperative conditions. For the 32 patients, the time to post-operative first flatus was 1(1,2)days, the time to postoperative first defecation was 1(1,3)days, the time to postoperative first intake of liquid food was 1(1,3)days, the duration of postoperative drainage tube indwelling was 3(3,6)days, the postoperative hospital stay was 6(5,14)days, and the time to relief of postoperative dysphagia was 5(5,8)days. No obvious hiccup was observed in any patient in the short term after surgery. (3) Follow-up. All 32 patients were followed up for 7.5(range, 3.0-11.0)months. Among the 32 patients, 26 cases achieved subjective relief of overall postoperative digestive tract symptoms, and 32 cases achieved subjective relief of overall postoperative respiratory tract symptoms. The proton pump inhibitor (PPI) withdrawal rate was 84.4%(27/32), and the treatment satisfaction rate was 87.5%(28/32). The incidences of postoperative complications inclu-ding abdominal distension, dysphagia, diarrhea, and increased flatus were 21.9%(7/32), 18.8%(6/32), 6.3%(2/32), and 3.1%(1/32), respectively. Dysphagia was significantly relieved in all affected patients within 2 months after surgery, and no patient had persistent dysphagia by the end of the follow-up period. There was no death, symptom recurrence, or reoperation.Conclusion:HHR-TEF-DDSF is safe and feasible in the treatment of gastroesophageal reflux disease, with favorable short-term efficacy.

Objective To investigate the influencing factors associated with early neurological deterioration(END)in patients with minor acute ischemic stroke(mAIS),develop a clinical prediction model for END,and identify independent risk factors for 90-day neurological functional outcomes after stroke.Methods mAIS patients admitted consecutively to the Department of Neurology,Yijishan Hospital of Wannan Medical College(the First Affiliated Hospital of Wannan Medical College),from July 2023 to July 2024 were retrospectively collected.A minor ischemic stroke was defined as acute ischemic stroke with a National Institutes of Health stroke scale(NIHSS)score≤5 on admission.Baseline,clinical,and imaging data of all mAIS patients were collected and recorded,including demographic information(age,sex),past medical history(hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease,atrial fibrillation),smoking history,alcohol consumption,baseline blood pressure,pre-onset modified Rankin scale(mRS),NIHSS scores at admission and during hospitalization(24 hours,48 hours,72 hours after admission),motor component subscore of the NIHSS scores,NIHSS scores at discharge,trial of Org 10172 in acute stroke treatment(TOAST)classification,laboratory indicators(fasting blood glucose,hemoglobin A1c[HbA1c],total cholesterol,triglycerides,high-density lipoprotein,low-density lipoprotein),clinical treatment information(intravenous thrombolysis,mono antiplatelet therapy,dual antiplatelet therapy,anticoagulation therapy)and length of stay.The status of stenosis and occlusion in the culprit vessel were assessed based on imaging results.Mild-to-moderate stenosis was defined as a stenosis rate of 0％to 69％,severe stenosis as a stenosis rate of 70％to 99％,and occlusion as complete interruption of the supplying artery.END was defined as an increase in NIHSS score of ≥2 points from baseline within 72 hours after admission,combined with an increase of at least 1 point in the motor score compared to the score at admission.Prognosis was assessed via telephone follow-ups at 90-day after onset using mRS score,with an mRS score ≤ 2 indicating a favorable outcome and an mRS score＞2 indicating a poor outcome.Variables with P＜0.05 in the univariate analysis were incorporated into multivariate Logistic regression analysis to identify the independent risk factors for END in mAIS patients.A nomogram model was constructed,and calibration curves along with decision curve analysis were plotted to evaluate the model's goodness-of-fit and clinical utility.Univariate and multivariate Logistic regression analyses were performed to identify factors associated with poor 90-day functional outcome after mAIS.Results(1)A total of 826 patients were included,aged 33-94 years,with a median age of 67(57,76)years.There were 571 males and 255 females.The NIHSS score at admission ranged from 0 to 5,with a median NIHSS score at admission of 3(2,4).The NIHSS motor subscore at admission ranged from 0 to 5,with a median baseline NIHSS motor score of 2(0,2).Among them,119 patients(14.4％)were in the END group and 707 patients(85.6％)were included in the non-END group.At 90days after stroke,744 patients(90.1％)had a favorable outcome,while 82 patients(9.9％)had a poor outcome.(2)Univariate analysis showed that there were statistically significant differences between the END group and the non-END group in terms of HbA1c,fasting blood glucose,baseline NIHSS score,baseline NIHSS motor subscore,history of alcohol consumption,diabetes mellitus,culprit vessel stenosis and occlusion,and TOAST classification(all P＜0.05).Statistically significant differences were observed between the favorable outcome group and the poor outcome group in HbA1c,fasting blood glucose,incidence of END,baseline NIHSS score,discharge NIHSS score,culprit vessel stenosis and occlusion,TOAST classification,and history of alcohol consumption(all P＜0.05).(3)Multivariate Logistic regression analysis indicated that mAIS patients with severe stenosis of the culprit vessel(OR,5.88,95％CI2.32-14.91,P＜0.01),occlusion of the culprit vessel(OR,5.74,95％CI 2.25-14.62,P＜0.01),history of alcohol consumption(OR,5.59,95％CI3.41-9.17,P＜0.01),elevated HbA1c(OR,1.67,95％CI 1.35-2.08,P＜0.01),and higher baseline NIHSS motor score(OR,1.43,95％CI 1.08-1.89,P=0.012)had an increased risk of END.A higher discharge NIHSS score(OR,2.59,95％CI 1.89-3.57,P＜0.01)and the occurrence of END(OR,18.42,95％CI 5.13-66.18,P＜0.01)were associated with poor 90-day functional outcome after mAIS.(4)The nomogram model constructed based on independent risk factors of END in mAIS patients demonstrated an AUC of 0.78(95％CI 0.73-0.83)for predicting END,with a sensitivity of 0.8 and a specificity of 0.7.The model showed good calibration,and the Hosmer-Lemeshow test indicated good agreement between predicted and observed values(P=0.333).Decision curve analysis revealed that the model provided a high net benefit across a range of high-risk thresholds(0.1-0.7),suggesting its potential clinical utility.Conclusions Severe stenosis of the culprit vessel,occlusion of the culprit vessel,glycated hemoglobin levels,baseline NIHSS motor subscale scores,and history of alcohol consumption are independent risk factors for END in patients with mAIS.The nomogram model constructed based on these factors demonstrated good predictive performance.END and NIHSS scores at discharge are independent predictors of poor 90-day outcomes in patients with mAIS.

Objective To investigate the impact of dexamethasone(DEX)on diaphragmatic atrophy caused by acute respiratory distress syndrome(ARDS)and its correlation with diaphragmatic protein metabolism.Methods Twenty healthy male Sprague-Dawley(SD)rats were randomly assigned to control,ARDS model,low-dose DEX,and high-dose DEX group,with each group consisting of five rats.ARDS was induced in the rats by intratracheal administration of lipopolysaccharide(LPS)at 4 mg/kg.Conversely,intratracheal saline was administered to the control group at 2 mL/kg.Following the induction of the model,an intraperitoneal injection of DEX at 1 mg·kg-1·d-1 was administered to the low-dose DEX group.Conversely,DEX at 5 mg·kg-1·d-1 was administered to the high-dose group for 7 consecutive days.Subsequently,on the eighth day of the experiment,the diaphragmatic weight of all rats was measured.Real-time quantitative polymerase chain reaction(PCR)was utilized to assess the mRNA expression of interleukins(IL-1β,IL-18)in each group.Western blotting was employed to determine the protein expression levels of nuclear factor-κB(NF-κB)p65,NOD-like receptor protein 3(NLRP3),caspase-1,Gasdermin D(GSDMD),myosin heavy chain 2(Myh2),and F-box protein 32(Fbxo32).Additionally,immunohistochemistry was utilized to evaluate the ratio of fast to slow muscle fibers in the diaphragm.Results The ARDS model group showed significant reductions in body weight,diaphragm weight,fast muscle fibers,and Myh2 protein expression compared to the control group[body weight(g):266±17 vs.292±15,diaphragm weight(g):0.77±0.02 vs.0.92±0.08,fast muscle fibers:(74±1)%vs.(78±3)%,Myh2 protein expression(Avalue):0.75±0.07 vs.0.95±0.05,all P<0.05].Conversely,significant increases were observed in the expressions of IL-1β and IL-18 mRNA,slow muscle fibers,and the proteins NF-κB p65,NLRP3,caspase-1,GSDMD,Fbxo32[IL-1β mRNA(IL-1β/GAPDH):2.2±0.3 vs.1.0±0.2,IL-18 mRNA(IL-18/GAPDH):2.3±0.3 vs.1.0±0.3,slow muscle fibers:(26±1)%vs.(22±3)%,NF-κB p65 protein expression(A value):0.40±0.15 vs.0.17±0.05,NLRP3 protein expression(A value):0.51±0.05 vs.0.27±0.08,caspase-1 protein expression(A value):0.54±0.12 vs.0.30±0.19,GSDMD protein expression(A value):0.40±0.12 vs.0.20±0.05,Fbxo32 protein expression(A value):0.51±0.15 vs.0.33±0.08,all P<0.05].Compared with the ARDS group,both low and high doses of DEX were found to further reduce body weight,diaphragm weight,fast muscle fibers,and Myh2 protein expression,and further increase the expressions of IL-1β and IL-18 mRNA,slow muscle fibers,and the proteins NF-κB p65,NLRP3,caspase-1,GSDMD,Fbxo32,with the changes in the high dose DEX group being more significant than those in the low dose group[body weight(g):198±14 vs.222±16,diaphragm weight(g):0.57±0.04 vs.0.68±0.04,fast muscle fibers:(56±5)%vs.(69±2)%,Myh2 protein expression(A value):0.29±0.16 vs.0.57±0.15,IL-1βmRNA expression:5.6±1.4 vs.3.3±0.6,IL-18 mRNA expression(IL-18/GAPDH):5.8±1.2 vs.3.9±0.6,slow muscle fibers:(44±5)%vs.(31±2)%,NF-κB p65 protein expression(A value):0.87±0.04 vs.0.70±0.07,NLRP3 protein expression(A value):0.75±0.08 vs.0.63±0.04,caspase-1 protein expression(A value):0.99±0.06 vs.0.82±0.08,GSDMD protein expression(Avalue):0.85±0.11 vs.0.61±0.10,Fbxo32 protein expression(Avalue):1.00±0.10 vs.0.78±0.12,all P<0.05].Normal muscle fiber structure was revealed by microscopic observation in the control group,clear fiber separation in the ARDS model group,and disordered muscle fiber arrangement with structural distortion was noted in both low and high-dose DEX groups.Conclusion Prolonged administration of DEX may worsen diaphragmatic atrophy induced by ARDS,possibly by promoting the activation of the NLRP3 inflammasome and cell pyroptosis.

Objective:To evaluate the dosimetric characteristics of Zap-X system and CyberKnife (CK) G4 system of stereotactic radiosurgery (SRS) for single brain metastasis.Methods:Twelve patients with single brain metastasis had been treated with CK were selected retrospectively. The prescribed dose of planning target volume (PTV) was 18-24 Gy for 1-3 fractions. The PTV was ranged from 0.44 to 11.52 cm 3. The 12 patients were re-planned in the Zap-X planning system using the same prescription dose and organs at risk constraints, and the prescription dose of PTV was normalized to 70% for both Zap-X and CK. The planning parameters and dosimetric parameters of PTV and organs at risk were compared and evaluated between two plans. All data were read at MIM Maestro. A paired Wilcoxon' signed-rank test was adopted for statistical analysis. A P value of less than 0.05 was considered as statistical significance. Results:For the target coverage, CK was significantly higher than Zap-X (99.14±0.57% vs. 97.55±1.34%, P<0.01), but Zap-X showed a higher conformity index (0.81±0.05 vs. 0.77±0.07, P<0.05), a lower Paddick gradient index (2.98±0.24 vs. 3.15±0.38), and a higher gradient score index (GSI) than CK. The total monitor unit (MU) of Zap-X was significantly lower than that of CK (11 627.63 ±5 039.53 vs. 23 522.16 ±4 542.12, P<0.01) and the treatment time was shorter than that of CK [(25.08 ±6.52) vs. (38.08 ±4.74) min, P<0.01]. Zap-X had lower dose volumes than CK for the dose of brain ( P<0.05). Zap-X had a lower D mean and D max of brainstem (both P<0.05), but a higher value of eyes and lens. For optic nerves and optic chiasm, there were no significant differences between two groups. In addition, for the protection of skin (V 22.5 Gy), Zap-X seemed better than CK [(4.15±4.48) vs. (4.37±4.50) cm 3, P<0.05]. Conclusions:For SRS treating single brain metastasis, Zap-X could provide a high quality plan equivalent to or even better than CK, especially reducing the treatment time. With continuous improvement and upgrading of Zap-X system, it may become a new SRS platform for the treatment of brain metastasis.

OBJECTIVE: To evaluate the effect of curcumin on renal mitochondrial oxidative stress, nuclear factor-κB/NOD-like receptor protein 3 (NF-κB/NLRP3) inflammatory body signaling pathway and tissue cell injury in rats with acute respiratory distress syndrome (ARDS). METHODS: A total of 24 specific pathogen free (SPF)-grade healthy male Sprague-Dawley (SD) rats were randomly divided into control group, ARDS model group, and low-dose and high-dose curcumin groups, with 6 rats in each group. The ARDS rat model was reproduced by intratracheal administration of lipopolysaccharide (LPS) at 4 mg/kg via aerosol inhalation. The control group was given 2 mL/kg of normal saline. The low-dose and high-dose curcumin groups were administered 100 mg/kg or 200 mg/kg curcumin by gavage 24 hours after model reproduction, once a day. The control group and ARDS model group were given an equivalent amount of normal saline. After 7 days, blood samples were collected from the inferior vena cava, and the levels of neutrophil gelatinase-associated lipocalin (NGAL) in serum were determined by enzyme-linked immunosorbent assay (ELISA). The rats were sacrificed, and kidney tissues were collected. Reactive oxygen species (ROS) levels were determined by ELISA, superoxide dismutase (SOD) activity was detected using the xanthine oxidase method, and malondialdehyde (MDA) levels were determined by colorimetric method. The protein expressions of hypoxia-inducible factor-1α (HIF-1α), caspase-3, NF-κB p65, and Toll-like receptor 4 (TLR4) were detected by Western blotting. The mRNA expressions of HIF-1α, NLRP3, and interleukin-1β (IL-1β) were detected by reverse transcription-polymerase chain reaction (RT-PCR). Renal cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). The morphological changes in renal tubular epithelial cells and mitochondria were observed under a transmission electron microscope. RESULTS: Compared with the control group, the ARDS model group exhibited kidney oxidative stress and inflammatory response, significantly elevated serum levels of kidney injury biomarker NGAL, activated NF-κB/NLRP3 inflammasome signaling pathway, increased kidney tissue cell apoptosis rate, and renal tubular epithelial cell damage and mitochondrial integrity destruction under transmission electron microscopy, indicating successful induction of kidney injury. Following curcumin intervention, the injury to renal tubular epithelial cells and mitochondria in the rats was significantly mitigated, along with a noticeable reduction in oxidative stress, inhibition of the NF-κB/NLRP3 inflammasome signaling pathway, and a significant decrease in kidney tissue cell apoptosis rate, demonstrating a certain dose-dependency. Compared with the ARDS model group, the high-dose curcumin group exhibited significantly reduced serum NGAL levels and kidney tissue MDA and ROS levels [NGAL (μg/L): 13.8±1.7 vs. 29.6±2.7, MDA (nmol/g): 115±18 vs. 300±47, ROS (kU/L): 75±19 vs. 260±15, all P < 0.05], significantly down-regulated protein expressions of HIF-1α, caspase-3, NF-κB p65, and TLR4 in the kidney tissue [HIF-1α protein (HIF-1α/β-actin): 0.515±0.064 vs. 0.888±0.055, caspase-3 protein (caspase-3/β-actin): 0.549±0.105 vs. 0.958±0.054, NF-κB p65 protein (NF-κB p65/β-actin): 0.428±0.166 vs. 0.900±0.059, TLR4 protein (TLR4/β-actin): 0.683±0.048 vs. 1.093±0.097, all P < 0.05], and significantly down-regulated mRNA expressions of HIF-1α, NLRP3, and IL-1β [HIF-1α mRNA (2^-ΔΔCt): 2.90±0.39 vs. 9.49±1.87, NLRP3 mRNA (2^-ΔΔCt): 2.07±0.21 vs. 6.13±1.32, IL-1β mRNA (2^-ΔΔCt): 1.43±0.24 vs. 3.95±0.51, all P < 0.05], and significantly decreased kidney tissue cell apoptosis rate [(4.36±0.92)% vs. (27.75±8.31)%, P < 0.05], and significantly increased SOD activity (kU/g: 648±34 vs. 430±47, P < 0.05). CONCLUSIONS Curcumin can alleviate kidney injury in ARDS rats, and its mechanism may be related to the increasing in SOD activity, reduction of oxidative stress, and inhibition of the activation of the NF-κB/NLRP3 inflammasome signaling pathway.
Male ; Rats ; Animals ; Rats, Sprague-Dawley ; NF-kappa B ; Actins ; Caspase 3 ; Curcumin ; Lipocalin-2 ; Toll-Like Receptor 4 ; Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; Reactive Oxygen Species ; Saline Solution ; Kidney ; Superoxide Dismutase

Objective:To investigate the effect of curcumin on renal fibrosis in lipopolysaccharide (LPS) induced acute respiratory distress syndrome (ARDS) in adult SD rats.Methods:Twenty-four male SD rats were randomly (random number) divided into four groups: control group, ARDS group, low dose group, and high dose group ( n=6 per group). In the control group, the rats were given atomization intratracheal of standard saline 2 mL/kg; in the ARDS group, low-dose group, and high-dose group, the rats were given atomization intratracheal of 4 mg/kg LPS; in the low-dose group, the rats were given curcumin 100 mg/d by the oral administration, and in the high-dose group, the rats were given curcumin or 200 mg/d respectively. After seven days, the rats were sacrificed. The superoxide dismutase (SOD) activity and the content of malondialdehyde (MDA) and glutathione (GSH) in renal tissue were detected by colorimetric assay. Nuclear factor kappa-B p65 (NF-κB p65) and transforming growth factor-β1 (TGF-β1) were detected by Western blot. The expression of interleukin-6 (IL-6) mRNA, proline hydroxylase 3 (PHD3) mRNA, vascular endothelial growth factor (VEGF) mRNA and erythropoietin receptor (EPOR) mRNA were detected by quantitative real-time PCR (qRT-PCR). HE staining and Masson staining were used to assess pathological damage. One-way analysis of variance was used for comparison among multiple groups and SNK method was used for comparison between two groups. Results:Compared with the control group, the SOD activity and GSH content in the ARDS group, low-dose group, and high-dose group were significantly decreased (all P<0.05); the protein expression levels of MDA, NF-κB p65, and TGF-β1 were increased significantly, and IL-6 mRNA, PHD3 mRNA, VEGF mRNA, and EPOR mRNA were significantly upregulated (all P<0.05). HE staining showed inflammatory cell infiltration, and fibrogenesis in kidney tissue, and Masson staining showed deposition of collangen-like substance. Compared with the ARDS group, SOD activity and GSH content were increased, while the protein expression of NF-κB p65 and TGF-β1, IL-6 mRNA, PHD3 mRNA, VEGF mRNA, and EPOR mRNA were decreased significantly in the low-dose group and high-dose group (all P<0.05). Curcumin therapy reduced inflammatory cellular infiltration, and the deposition of collagen-like substance in kidney tissue. Compared with the low-dose group, SOD activity and GSH content were increased in the high-dose group (all P<0.05), and the protein expression of NF-κB p65 and TGF-β1, IL-6 mRNA, PHD3 mRNA, VEGF mRNA, and EPOR mRNA were decreased significantly in the high-dose group (all P<0.05). The high-dose group exhibited a significant reduction in edema, and a decrease of the deposition of collagen-like substance in kidney tissue. Conclusions:Curcumin can inhibit the development of renal fibrosis induced by acute respiratory distress syndrome in rats, and its mechanism may be related to inhibiting the expression of inflammatory factors and enhancing hypoxia tolerance.

Objective:To study the analgesic effect of α-cobratoxin (α-CbTX) on mice and its effect on protein kinase A (PKA) activity of spinal dorsal root ganglion (DRG) in mice.Methods:Healthy male ICR mice( n=102) were randomly divided into low-, medium-, and high-dose α-CbTX groups (1 mg/kg, 3 mg/kg, 9 mg/kg respectively, gavage, n=21), solvent control group (equivalent volume of 0.9% normal saline, gavage, n=21), morphine positive control group (3 mg/kg, intraperitoneal injection, n=6)or aspirin positive control group(300 mg/kg, gavage, n=12). The analgesic effect of α-CbTX was evaluated by hot plate test, acetic acid twisting test and formalin foot licking test. Formalin plantar injection was used to induce pain and then the L4-L6 DRG was taken 30 minutes later. The expression of PKA C-α in L4-L6 DRG of mice were detected by Western blot.SPSS 16.0 software was used for statistical analysis. Repeated measurement ANOVA was used to evaluate the hot plate experimental data, and one-way ANOVA was used for other experimental data. LSD- t test was used for further pairwise comparison. Results:In the hot plate test, the interaction between group and time of mice paw licking latency was significant ( F=8.902, P<0.05). At 0.5 h after administration, the paw licking latencies of α-CbTX medium-dose group ((11.83±1.47)s)and α-CbTX high-dose group (( 14.33±12.1)s) were both longer than that of solvent control group((8.17±0.75) s) ( t=4.461, 7.053, both P<0.05). The efficacy of α-CbTX medium dose group lasted until 1.5 h after administration (all P<0.05), and that of α-CbTX high dose group lasted until 2 h after administration(all P<0.05). In the acetic acid writhing test, the writhing times in the low-, medium- and high-dose α-CbTX group((34.50±3.62) times, (26.17±2.40) times, (13.83±3.76) times)) were significantly lower than that in solvent control group ((42.50±4.59) times) ( t=3.938, 8.040, 14.112, all P<0.05). In the period of the formalin test phase Ⅱ, the total licking time of α-CbTX low-, medium- and high-dose groups ((71.17±6.46) s), (54.67±6.41) s, (40.50±3.89)s) were significantly shorter than that of the solvent control group ((98.67±11.50) s)( t=6.950, 11.120, 14.700, all P<0.05). In the Western blot experiment, compared with solvent control group (0.22±0.01), the levels of PKA C-α in the DRG of mice in low-, medium- and high-dose α-CbTX groups ((0.31±0.02), (0.41±0.03), (0.44±0.02)) were up-regulated ( t=3.140, 6.471, 7.492, all P<0.05). Conclusion:α-CbTX has obvious analgesic effect, and its analgesic mechanism may be related to the activation of PKA.

Objective Toexploretheimagingfeaturesofextramedullarydisease(EMD)in multiplemyeloma(MM).Methods Theclinicalandimagingdataof17patientswithpathologicallydiagnosedMMcombinedwithEMDwereanalyzedretrospectively.Results EMDhadcertainpredilectionsites,Centralnervoussysteminvasion (6):meningealinvasion (3:1 multiple,2focal),spinalcanal invasion (1focal),thelefttemporalpoleinvasion(1focal),theleftsideforeheadinvasion(1focal);Headandneckinvasion(3:allfocal);Thoraxinvasion(8):pleuralinvasion(6:5 multiple,1focal),intrapulmonaryinvasion(1focal),anteriormediastinalinvasion(1focal);Subcutaneoussofttissueinvasion(5:allmultiple);Muscleinvasion(2focal);Lymphnodeinvasion (1 multiple).BothCTand MRI showedsofttissuenodulesormasses.ThevaluesofCTwereabout30~70HU,especiallyin30~45HU,whileMRIpresentedequal orslightlylowsignalonT1WI,equalorslightlyhighsignalonT2WI,andhighsignalinthesequenceofDWIcombinedwithmoderate toobviousenhancement,Generally,theboundaryofEMDwereclearandtheshapeoftheselesionswereregular,However,theinvasion tomuscleinsomelesionsshowedthepatternofinvasivegrowth.Conclusion EMDofmultiplemyelomamayhappenanywhere,and thepleural,meningesandsubcutaneoussofttissuesarethemostcommonlocation.CTandMRIcanshowtheEMDverywell.Thelocation, size,shapeandrelationshipwithsurroundingtissuesoftheselesionshavecertainreferencevaluesforthediagnosisanddifferential diagnosisofEMD.