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Objective:To evaluate the role of transient receptor potential vanillic acid 4 (TRPV4) in dexmedetomidine-induced improvement in cognitive function in mice with mechanical ventilator-caused brain injury.Methods:Ninety clean-grade healthy male C57BL6 mice, weighing 20-25 g, aged 8-12 weeks, were divided into 5 groups ( n=18 each) using a random number table method: control group (group C), mechanical ventilation group (group V), HC-067047 group (group H), dexmedetomidine group (group D), and dexmedetomidine+ GSK1016790A group (group DG). In group C, the animals breathed air spontaneously for 6 h without mechanical ventilation. In group V, the animals were mechanically ventilated for 6 h. In group H, TRPV4 blocker HC-067047 10 mmol was injected into the cerebral ventricle at 3 and 6 h of mechanical ventilation. In D and DG groups, dexmedetomidine 50 μg/kg was intraperitoneally injected at 30 min before mechanical ventilation. In group DG, TRPV4 agonist GSK1016790A 5 μmol was injected into the cerebral ventricle at 60 min before mechanical ventilation. Morris water maze test was performed on 6 mice in each group at 1 day before mechanical ventilation and 3 and 7 days after mechanical ventilation. Six mice in each group were randomly selected and sacrificed at 1 day after mechanical ventilation, and the brain tissue was taken for determination of the neuronal apoptosis in hippocampal CA1 area by TUNEL method, and the apoptosis index was calculated. Six mice in each group were randomly selected and sacrificed at 1 day after mechanical ventilation, and the hippocampal tissues were taken for determination of the expression of TRPV4, serine-threonine protein kinase (Akt), phosphorylated Akt (p-Akt), Bcl-2, Bax and caspase-3 by Western blot. Results:Compared with group C, the escape latency was significantly prolonged and the number of crossing the original platform was reduced at 3 and 7 days after mechanical ventilation, the expression of TRPV4 and caspase-3 was up-regulated, the ratio of Bcl-2/Bax was decreased, and the apoptosis index of neurons was increased in group V and group DG ( P<0.05). Compared with group V, the escape latency was significantly shortened and the number of crossing the original platform was increased at 3 and 7 days after mechanical ventilation, the expression of TRPV4 and caspase-3 was down-regulated, the expression of p-Akt was up-regulated, the ratio of Bcl-2/Bax was increased, and the apoptosis index of neurons was decreased in group D and group H ( P<0.05). Compared with group D, the escape latency was significantly prolonged at 3 and 7 days after mechanical ventilation, the number of crossing the original platform was reduced, the expression of TRPV4 and caspase-3 was up-regulated, the expression of p-Akt was down-regulated, the ratio of Bcl-2/Bax was decreased, and the apoptosis index of neurons was increased in group DG ( P<0.05). Conclusions:TRPV 4 is involved in dexmedetomidine-induced improvement in cognitive function, which is related to up-regulation of p-Akt expression and inhibition of apoptosis in hippocampal neurons in mice with mechanical ventilation-caused brain injury.
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Objective:To compare the predictive efficacy of different versions of Briganti nomogram in predicting lymph node metastasis in Chinese patients with prostate cancer.Methods:From October 2012 to April 2021, 583 cases with prostate cancer who underwent radical prostatectomy and pelvic lymphadenectomy by a single surgeon were retrospectively collected. For all 583 patients, the median age was 67 (63, 72)years old, median BMI was 24.39(22.58, 26.35)kg/m 2, median PSA was 22(12, 43)ng/ml. There were 65 cases, 357 cases, 140 cases and 21 cases with clinical stage T 1, T 2, T 3 and T 4. There were 30 cases, 109 cases, 104 cases, 160 cases and 180 cases for ISUP 1 group, 2 group, 3 group, 4 group and 5 group. The median percentage of positive biopsy cores was 50%(33%-83%). The validated nomograms were Briganti's 2006, 2012 and 2017. Compared with the 2006 edition, the new variables in the 2012 edition and 2017 edition were the percentage of positive biopsy cores, the percentage of the highest grade positive biopsy cores and the percentage of the lower grade positive biopsy cores, respectively. The validation patients for the 2006, 2012 and 2017 versions of nomogram were 560, 513 and 357, respectively, which were used as the differential validation cohorts. A total of 357 patients were validated for all three versions of nomogram, which was considered as the general validation cohort. The area under the receiver operating characteristic (ROC) curve (AUC), calibration curve and clinical decision curve analysis were used to evaluate the predictive efficacy of the three versions of nomograms. Results:In the differential validation cohort, the AUC values of the 2006, 2012 and 2017 versions of the nomogram were 0.738(95% CI 0.690-0.785), 0.765(95% CI 0.717-0.814) and 0.779(95% CI 0.724-0.834), respectively. There was no significant difference in AUC values among versions ( P>0.05). In the general validation cohort, the AUC values of the three versions of the nomogram were as follows 0.744(95% CI 0.682-0.805), 0.759(95% CI 0.700-0.818) and 0.779(95% CI 0.724-0.834), respectively. There was no significant difference in AUC values among the three versions ( P>0.05). The calibration curve showed that the prediction probability of 2012 and 2017 editions was in good agreement with the actual risk within the prediction probability of 0-40%. Analysis of the clinical decision curve showed that the clinical benefit of the 2012 version was greater than that of the other two versions in the prediction threshold of 0-33%. Conclusion:Briganti nomogram is suitable for predicting pelvic lymph node metastasis in Chinese patients with prostate cancer. The 2012 and 2017 versions of the nomogram have good predictive performance, and the versions can be selected according to the predictive variables that can be provided.
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Objective:To investigate the effect of baicalin on cognitive function of mice with brain injury induced by mechanical ventilation and its mechanism.Methods:Seventy two C57BL6 mice, weighing 20-25 g, aged 8-12 weeks, were randomly divided into control group (group C), mechanical ventilation group (group V), baicalin group (group B), baicalin+ Akt inhibitor MK-2206 group (group BM) according to random number table method, with 18 in each group.Mice in group C did not have mechanical ventilation and breathed air independently for 6 hours.Mice in group V received mechanical ventilation for 6 hours.Mice in group B and group BM were intraperitoneally injected with baicalin 100 mg/kg 30 minutes before mechanical ventilation, and mice in group BM were injected intraventricular with Akt inhibitor MK-2206 300 μg/kg 60 minutes before mechanical ventilation.Six mice in each group were randomly selected to test their learning and memory abilities by Morris water maze test 1st day before mechanical ventilation and 3rd day and 7th day after mechanical ventilation.One day after mechanical ventilation, six mice in each group were killed, and the brain tissue was taken.TUNEL method was used to detect the neuronal apoptosis in hippocampal CA1 area, and the apoptosis index was calculated.One day after mechanical ventilation, six mice in each group were killed, and the hippocampus was taken, Western blot was used to detect the protein expressions of caspase-3, caspase-9, Akt, p-Akt, GSK-3β and p-GSK-3β.SPSS 22.0 software was used for statistical analysis of data, repeated measure ANOVA and one-way ANOVA were used for comparison between multiple groups.LSD- t test was used for further pairwise comparison. Results:The results of water maze test showed that the time and group interaction of the four groups were not significant ( F=1.14, P>0.05), the main effect of time and group were both significant ( F=47.36, 59.65, both P<0.05). At 3rd day and 7th day after mechanical ventilation, the escape latencies of mice in group V were higher than those in group C (both P<0.05), and the numbers of platform crossing were lower than those in group C (both P<0.05). And 3 days and 7 days after mechanical ventilation, the escape latencies of mice in group B were lower than those in group V (both P<0.05) and the numbers of platform crossing were higher than those in group V (both P<0.05). The escape latenies of mice in BM group on the 3rd and 7th day were higher than those in group B (both P<0.05), and the numbers of platform crossing were lower than those in group B on the 3rd day and 7th day after mechanical ventilation(both P<0.05). TUNEL and Western blot results showed that apoptosis index of hippocampal neurons and expression levels of apoptosis-related proteins caspase-3 and caspase-9 were significant different in the four groups ( F=51.42, 41.21, 40.19, all P<0.05). The apoptosis index of hippocampal neurons ((40.6±3.9)%), the expression levels of caspase-3 (4.93±0.92) and caspase-9 (4.81±0.88) in the hippocampus of mice in group V were higher than those in group C ((13.7±1.4)%, (1.87±0.27), (1.71±0.25), all P<0.05), the apoptosis index of hippocampal neurons ((15.6±1.6)%), the expression levels of caspase-3 (1.95±0.30) and caspase-9 (1.76±0.28) in group B were lower than those in group V ((40.6±3.9)%, (4.93±0.92), (4.81±0.88), all P<0.05), the apoptosis index of hippocampal neurons ((27.8±2.7)%), the expression levels of caspase-3 (3.58±0.61) and caspase-9 (3.49±0.57) in BM group were higher than those in group B ((15.6±1.6)%, (1.95±0.30), (1.76±0.28), all P<0.05). Expression level of p-Akt, p-GSK-3β in hippocampal tissues of the four group of mice were significantly different ( F=37.54, 43.23, both P<0.05). The expression level of p-Akt (0.51±0.06) and p-GSK-3β (0.47±0.05) of hippocampal tissues of mice in group V were lower than those of group C ((1.07±0.10), (1.11±0.12), both P<0.05), the expression level of p-Akt (0.99±0.10) and p-GSK-3β (1.08±0.09) of hippocampal tissues of mice in group B were higher than those of group V (both P<0.05), the expression level of p-Akt (0.83±0.08) and p-GSK-3β (0.81±0.07) of hippocampal tissues of mice in group BM were lower than those in group B (both P<0.05). Conclusion:Baicalin can improve the cognitive function of mice with brain injury induced by mechanical ventilation, which is related with activation of Akt/GSK-3β signaling pathway and inhibition of hippocampal neuron apoptosis.
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Objective:To evaluate the role of transient receptor potential vanilloid receptor 1 (TRPV1)/nuclear factor-κB (NF-κB) signaling pathway in dexmedetomidine-induced alleviation of ventilator-induced lung injury (VILI) in rats.Methods:One hundred clean-grade healthy male Sprague-Dawley rats, weighing 270-320 g, aged 4-5 months, were divided into 5 groups ( n=20 each) using a random number table method: control group (group C), VILI group (group V), AMG9810 group (group A), dexmedetomidine group (group D), and dexmedetomidine + RTX group (group DR). VILI model was prepared by mechanical ventilation with a tidal volume of 40 ml/kg for 4 h. In group A, TRPV1 inhibitor AMG9810 30 mg/kg was intraperitoneally injected at 1 h before mechanical ventilation.Dexmedetomidine 5.0 μg/kg was intravenously infused at 20 min before mechanical ventilation, and dexmedetomidine was intravenously infused at the rate of 5.0 μ g·kg -1·h -1 during ventilation in group D and group DR.In group DR, RTX 70 μ g/kg was intraperitoneally injected for 3 consecutive days before mechanical ventilation.At 4 h of mechanical ventilation, the concentrations of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-6 in bronchoalveolar lavage fluid (BALF) were detected, oxygenation index (OI) and wet/dry lung weight (W/D) ratio were measured, the histopathological changes of lung tissues were observed, and lung injury was assessed and scored.The expression of TRPV1 and NF-κB in lung tissues was detected by Western blot, and real-time polymerase chain reaction was used to detect the expression of TRPV1 and NF-κB mRNA. Results:Compared with group C, the concentrations of IL-1β, TNF-α and IL-6 in BALF were significantly increased, OI was decreased, the W/D ratio and lung injury scores were increased, and the expression of TRPV1 and NF-κB protein and mRNA was up-regulated in group V ( P<0.05). Compared with group V, the concentrations of IL-1β, TNF-α and IL-6 in BALF were significantly decreased, OI was increased, the W/D ratio and lung injury scores were decreased, and the expression of TRPV1 and NF-κB protein and mRNA was down-regulated in A, D and DR groups ( P<0.05). Compared with group D, the concentrations of IL-1β, TNF-α and IL-6 in BALF were significantly increased, OI was decreased, the W/D ratio and lung injury scores were increased, and the expression of TRPV1 and NF-κB protein and mRNA was up-regulated in group DR ( P<0.05). Conclusions:The mechanism by which dexmedetomidine alleviates VILI is partially related to inhibition of the activation of TRPV1/NF-κB signaling pathway and inhibition of the inflammatory responses in lung tissues of rats.
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Objective:To evaluate the effects of dexmedetomidine on alveolar epithelial barrier function in rats with ventilator-induced lung injury (VILI), and the role of protein kinase C (PKC).Methods:One hundred clean-grade male Sprague-Dawley rats, weighing 270-320 g, aged 4-5 months, were divided into 5 groups ( n=20 each) using a random number table method: control group (group C), VILI group (group V), PKC inhibitor group (group B), dexmedetomidine group (group D), and dexmedetomidine plus PKC agonist group (DP group). The VILI model was developed by mechanical ventilation with a tidal volume of 40 ml/kg for 4 h in anesthetized animals.Group C breathed air autonomously for 4 h without mechanical ventilation.Group V was mechanically ventilated for 4 h. In group B, bisindolvlmaleimide I 0.12 mg/kg was injected intramuscularly 1 h before mechanical ventilation.In D and DP groups, dxmedetomidine 5.0 μg/kg was injected intravenously at 20 min before mechanical ventilation, and dexmedetomidine was intravenously infused at the rate of 5.0 μg·kg -1·h -1 during mechanical ventilation.In group DP, PKC agonist phorbol-12-myristic acid-13-acetate 15 μg/kg was intraperitoneally injected at 30 min before mechanical ventilation.At 4 h of mechanical ventilation, oxygenation index (OI), lung permeability index (LPI) and wet/dry lung weight (W/D) ratio were measured, the pathological changes of lung tissues were observed, and lung injury was assessed and scored.The expression of PKC, occludin and ZO-1 protein was detected by Western blot, and the expression of PKC mRNA, occludin mRNA and ZO-1 mRNA was determined by real-time polymerase chain reaction. Results:Compared with group C, OI was significantly decreased, LPI, W/D ratio and lung injury score were increased, the expression of PKC protein and mRNA was up-regulated, and the expression of occludin and ZO-1 protein and mRNA was down-regulated in V and DP groups ( P<0.05), and no significant change was found in the parameters mentioned above in B and D groups ( P>0.05). Compared with group V, OI was significantly increased, LPI, W/D ratio and lung injury score were decreased, the expression of PKC protein and mRNA was down-regulated, and the expression of occludin and ZO-1 protein and mRNA was up-regulated in B, D and DP groups ( P<0.05). Compared with group D, OI was significantly decreased, LPI, W/D ratio and lung injury score were increased, the expression of PKC protein and mRNA was up-regulated, and the expression of occludin and ZO-1 protein and mRNA was down-regulated in group DP ( P<0.05). Conclusions:Dexmedetomidine can reduce the damage to alveolar epithelial barrier function in rats with VILI, and the mechanism is related to inhibition of PKC activation and up-regulation of the expression of occludin and ZO-1.
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Objective:To evaluate the safety and efficacy of Toumai ? endoscopic robotic system in radical prostatectomy. Methods:This study was a single-center phase Ⅲ randomized controlled study. From June 2020 to January 2021, patients with prostate cancer who met the inclusion criteria in Changhai Hospital Affiliated to Naval Military Medical University were divided into the experimental group and the control group by random table method. Inclusion criteria included aged 18 to 80 years, pathologically diagnosed as prostate cancer, clinical stage ≤T 2N 0M 0. Exclusion criteria included patients requiring emergency surgery, having serious cardiovascular diseases and cannot tolerate surgery, having participated in other investigational drug or device clinical trials within the last 3 months. The experimental group used Toumai ? laparoscopic robotic system, and the continence group used the Da Vinci robotic system. The patients in both groups underwent radical prostatectomy via a transabdominal approach, which was performed by two surgeons. The clinical characteristics between the two groups were compared, related adverse events were recorded, and PSA and urinary continence were followed up one month after the operation. Results:A total of 44 patients were enrolled in this study, including 22 cases in the experimental group and 22 cases in the control group. The mean age of patients in the trial group and the control group was (67.7±7.5) years and (66.4±6.3) years, respectively. The median PSA at diagnosis was 10.5 (7.7, 23.7) ng/ ml and 13.5 (8.9, 24.7) ng/ ml, respectively. Biopsy Gleason score of 6, 7, 8 and 9 in experimental group were 13.6% (3/22), 68.2% (15/22), 4.5% (1/22) and 13.6% (3/22), respectively, and in the control group were 4.5% (1/22), 59.1% (13/22), 22.7% (5/22) and 13.6% (3/22) respectively. The middle risk and high risk group in the experimental group was 50.0% (11/22), 50.0% (11/22), and the control group was 36.4% (8/22), 63.6% (14/22). There was no statistical difference between the two groups.The operations in both groups were successfully performed. There were no conversions to open or laparoscopic surgeries, and no Clavien-Dindo grade Ⅲcomplications. There was no significant difference in the estimated blood loss during the operation [(109.1±51.6)ml vs.(94.5±51.6)ml] and the blood transfusion rate [9.1%(2/22)vs. 4.5%(1/22)] in both groups. The operation time was significantly higher in the experimental group than that in the control group [164.5(130.5, 214.3) min vs. 88.0(65.3, 110.5)min, P<0.001]. The positive rate of surgical margin was 13.6% (3/22) in the experimental group and 36.4% (8/22) in the control group, respectively, showing no significant difference. The pathologic stages of pT 2, pT 3a and pT 3bin experimental group were 63.6% (14/22), 13.6% (3/22) and 22.7% (5/22), respectively, while those in control group were 36.3% (8/22), 40.9% (9/22) and 22.7% (5/22), respectively, showing no significant difference. The recovery rates of urine control in the experimental group and the control group were 22.7% (5/22) and 22.7% (5/22), respectively. The median PSA in the experimental group and the control group were 0.055 (0.021, 0.103) ng/ ml and 0.032 (0.010, 0.089) ng/ ml, respectively, with no statistical difference. Conclusions:The Toumai ? endoscopic robotic system can successfully perform radical prostatectomy, based on insignificant difference from Da Vinci robotic system in safety and efficacy. The short-term follow-up showed that tumor control and urinary continence have recovered well in the test group. The long-term effect of the new system on tumor control and functional recovery after radical prostatectomy needs further multi-center studies.
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Objective:To explore the effect of the location and size of region of interest (ROI) on the measurement of liver fat by means of quantitative computed tomography (QCT).Methods:A total of 98 subjects who were examined with QCT for bone mineral density examination from December 25, 2019 to January 17, 2020 were recruited continuously from the Department of Health Management of Henan Provincial People′s Hospital. The liver fat content was measured by QCT workstation. The ROI was located respectively in the left lobe, the right anterior lobe and the right posterior lobe of the liver, and it was measured independently by the A measurer and B measurer. The central position of the ROI was fixed and the diameter was increased, and it was measured by the A measurer. In this study, Friedman test was used to compare the differences of measurement results in different positions or sizes of ROI, and intra-class correlation coefficients (ICC) was used to evaluate the repeatability of inter-measurers.Results:There was a significant difference for liver fat content under different positions of ROI (χ2=62.306, P<0.001), but no difference under different seizes of ROI (χ2=1.088, P=0.581). The ICC values of the inter-measurers repeatability analysis of the A measurer and B measurer in the left lobe, right anterior lobe and right posterior lobe of the liver were 0.847, 0.917 and 0.874, all more than 0.75, and the reproducibility was good. Conclusions:When QCT technique is applied to the measurement of liver fat content, the location conditions of ROI may affect results, so it is necessary to select multiple ROI in the whole liver for measurement. The inter-measurers repeatability of QCT in different parts of the liver is good.
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Objective:To evaluate the relationship between the mechanism underlying methylprednisolone-induced alleviation of ventilator-induced lung injury (VILI) and p38 mitogen-activated protein kinase (p38 MAPK)/nucleotide binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) pathway in lung tissues of rats.Methods:Sixty clean-grade male Sprague-Dawley rats, weighing 270-320 g, aged 4-5 months, were divided into 3 groups ( n=20 each) using a random number table method: control group (group C), mechanical ventilation group (group V), and methylprednisolone group (group M). Group C breathed air spontaneously for 4 h without mechanical ventilation.Group V was mechanically ventilated (RR 40 times/min, V T 40 ml/kg, I∶E 1∶1, PEEP 0, FiO 2 21%) for 4 h. Group M received intravenous methylprednisolone 10 mg/kg at 20 min before mechanical ventilation.At 4 h of mechanical ventilation, broncho-alveolar lavage fluid (BALF) was collected to measure the concentrations of interleukin-1beta (IL-1β), IL-18, and tumor necrosis factor-alpha (TNF-α) and wet/dry lung weight ratio (W/D ratio), and lung tissues were obtained for microscopic examination of the histopathological changes and for detection of the expression of p38MAPK, phosphorylated p38MAPK (p-p38MAPK), NLRP3, apoptosis-related speck-like protein containing a CARD (ASC), and cysteinyl aspartate-specific protease-1 (caspase-1) (using Western blot). Results:Compared with group C, the W/D ratio of lung tissues and concentrations IL-1β, IL-18 and TNF-α in BALF were significantly increased, and the expression of p-p38MAPK, NLRP3, ASC and caspase-1 was up-regulated in group V ( P<0.05), and no significant change was found in group M ( P>0.05). Compared with group V, the W/D ratio of lung tissues and concentrations of IL-1β, IL-18 and TNF-α in BALF were significantly decreased, and the expression of p-p38MAPK, NLRP3, ASC and caspase-1 was down-regulated in group M ( P<0.05). Conclusion:The mechanism by which methylprednisolone alleviates VILI may be related to inhibition of p38MAPK/NLRP3 pathway activity and reduction of inflammatory responses in lung tissues of rats.
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Hypoglossal motor neurons (HMNs) innervate tongue muscles and play key roles in a variety of physiological functions, including swallowing, mastication, suckling, vocalization, and respiration. Dysfunction of HMNs is associated with several diseases, such as obstructive sleep apnea (OSA) and sudden infant death syndrome. OSA is a serious breathing disorder associated with the activity of HMNs during different sleep-wake states. Identifying the neural mechanisms by which the state-dependent activities of HMNs are controlled may be helpful in providing a theoretical basis for effective therapy for OSA. However, the presynaptic partners governing the activity of HMNs remain to be elucidated. In the present study, we used a cell-type-specific retrograde tracing system based on a modified rabies virus along with a Cre/loxP gene-expression strategy to map the whole-brain monosynaptic inputs to HMNs in mice. We identified 53 nuclei targeting HMNs from six brain regions: the amygdala, hypothalamus, midbrain, pons, medulla, and cerebellum. We discovered that GABAergic neurons in the central amygdaloid nucleus, as well as calretinin neurons in the parasubthalamic nucleus, sent monosynaptic projections to HMNs. In addition, HMNs received direct inputs from several regions associated with respiration, such as the pre-Botzinger complex, parabrachial nucleus, nucleus of the solitary tract, and hypothalamus. Some regions engaged in sleep-wake regulation (the parafacial zone, parabrachial nucleus, ventral medulla, sublaterodorsal tegmental nucleus, dorsal raphe nucleus, periaqueductal gray, and hypothalamus) also provided primary inputs to HMNs. These results contribute to further elucidating the neural circuits underlying disorders caused by the dysfunction of HMNs.
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Objective@#To investigte the efficacy of docetaxel combined with androgen deprivation therapy for the treatment of metastatic hormone-sensitive prostate cancer based on Chinese population.@*Methods@#A total of 497 patients were enrolled from January 2004 to July 2018 in the Changhai Hospital. 459 patients received androgen deprivation therapy alone and 38 patients received androgen deprivation therapy combined with docetaxel. The mean age was (72.1±8.7)years. The median PSA level was 100.0 ng/ml, ranging 42.3-999.0 ng/ml. Patients of clinical T2, T3, T4 stage were 213(42.9%), 160(32.2%), 124(24.9%), respectively. Patients of clinical N0, N1, Nx stage were 319(64.2%), 144(29.0%), 34(6.8%), respectively. Patients of clinical M0, M1a, M1b, M1c, Mx stage were 100(20.1%), 51(10.3%), 332(66.8%), 9(1.8%), 5(1.0%), respectively. Gleason scores of biopsy showed that 146(29.4%) patients was ≤7, 103(20.7%) was 8 and 248(49.9%)was ≥9. Propensity score matching was used to match the baseline between groups. Caliper value was set at 0.02. SPSS 22 software was used to achieve a 1∶1 match between the two groups. There were no statistical difference in the age(P=0.102), PSA(P=0.713), T stage(P=0.113), N stage(P=0.226), M stage(P=0.514), Gleason score(P=0.612), tumor loading(P=0.812)between the two groups. The castration resistance-free rate and cancer specific survival rate of the two groups were compared by log-rank and breslow-wilcoxon test. Furthermore, forest plots were used to display the analysis results of different subgroups such as age, PSA, clinical stage, Gleason score, tumor load, whether patients had received palliative resection, and the differences in castration resistance-free rate were compared between the subgroups with high tumor load.@*Results@#The median follow-up time was 22.6 months in the androgen deprivation therapy group and 13.7 months in the combined therapy group. The number of patients with castration resistance in the two groups was 23 and 17, respectively. There were 3 and 6 deaths, respectively. There was no statistically significant difference in the overall progression time to castration resistance between the two groups (10.3 m vs. 16.5 m, P>0.05), and no statistically significant difference in the prostate cancer specific survival rate (21.9 m vs.14.8 m, P>0.05). When subgroup analysis was performed, it was found that patients in the high-metastasis-volume subgroup who received the combination therapy had a significantly longer castration resistance free lifetime (10.6 m vs. 7.2 m, P=0.044), but there was no significant difference in the low- metastasis-volume subgroup(10.5 m vs.12.6 m, P>0.05).@*Conclusion@#Docetaxel combined with androgen deprivation therapy can improve the castration resistance free rate in patients with high metastasis volume, but not in low metastasis volume group.
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BACKGROUND@#The role of local treatment in oligometastatic prostate cancer (PCa) is gaining interest with the oligometastases hypothesis proposed and the improvement of various surgical methods and techniques. This study aimed to compare the short-term therapeutic outcomes of robotic-assisted laparoscopic radical prostatectomy (RALP) for oligometastatic prostate cancer (OPC) vs. localized PCa using propensity score matching.@*METHODS@#Totally 508 consecutive patients underwent RALP as a first-line treatment. The patients were divided into two groups according to oligometastatic state: the OPC group (n = 41) or the localized PCa group (n = 467). Oligometastatic disease was defined as the presence of two or fewer suspicious lesions. The association between the oligometastatic state and therapeutic outcomes of RALP was evaluated, including biochemical recurrence (BCR) and overall survival (OS). A Cox proportional hazards model was used to assess the possible risk factors for BCR.@*RESULTS@#Totally 41 pairs of patients were matched. The median operative time, the median blood loss, the overall positive surgical margin rate, the median post-operative hospital stays, and the post-operative urinary continence recovery rate between the two groups showed no statistical significance. The 4-year BCR survival rates of the OPC group and localized PCa group were 56.7% and 60.8%, respectively, without a significant difference (P = 0.804). The 5-year OS rates were 96.3% and 100%, respectively (P = 0.326). Additionally, the results of Cox regression showed that oligometastatic state was not an independent risk factor for BCR (P = 0.682).@*CONCLUSIONS@#Our findings supported the safety and effectiveness of RALP in OPC. Additionally, oligometastatic state and sites did not have an adverse effect on BCR independently.
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Objective:To evaluate the effect of dexmedetomidine on the extracellular signal-regulated kinase(ERK)/sodium-potassium ATPase(Na + -K + -ATPase)signaing pathway in lung tissues of rats with mechanical ventilation-induced lung injury (VILI). Methods:Forty-eighty clean-grade male Sprague-Dawley rats, weighing 270-320 g, aged 4-5 months, were divided into 4 groups ( n=12 each) using a random number table method: control group (group C), VILI (alpha2-adrenergic receptor antagonist) group (group V), dexmedetomidine group (group D), and dexmedetomidine plus yohimbine group (group DY). Group C underwent no mechanical ventilation and breathed air spontaneously for 4 h. Mechanical ventilation (respiratory rate 40 breaths/min, tidal volume 40 ml/kg, inspiratory/expiratory ratio 1∶1, PEEP 0, fraction of inspired oxygen 21%) lasted 4 h in group V. Dexmedetomidine was infused intravenously in a dose of 5.0 μg/kg at 20 min before ventilation followed by an infusion of 5.0 μg·kg -1· h -1 throughout ventilation in group D. In group DY, yohimbine 0.1 mg/kg was injected intravenously at 10 min before dexmedetomidine, and the other treatments were similar to these previously described in group D. Blood samples and lung tissues were taken at 4 h of mechanical ventilation to determine the wet/dry weight ratio (W/D ratio), lung permeability index (LPI), alveolar fluid clearance rate (AFC), and expression of extracellular signal-regulated kinase (ERK), phosphorylated extracellular signal-regulated kinase (p-ERK), and Na + -K + -ATPase in lung tissues (by Western blot) and to observe pathological changes of lung tissues. Results:Compared with group C, LPI and W/D ratio were significantly increased, AFC was decreased, p-ERK expression was up-regulated, and Na + -K + -ATPase expression was down-regulated in group V and group DY ( P<0.05), and no significant change was found in the incidence of the parameters mentioned above in group D ( P>0.05). Compared with group V, LPI and W/D ratio were significantly decreased, AFC was increased, p-ERK expression was down-regulated, Na + -K + -ATPase expression was up-regulated ( P<0.05), and the pathological changes of lung tissues were significantly attenuated in group D, and no significant change was found in the incidence of the parameters mentioned above in group DY ( P>0.05). Compared with group D, LPI and W/D ratio were significantly increased, AFC was decreased, p-ERK expression was up-regulated, Na + -K + -ATPase expression was down-regulated ( P<0.05), and the pathological changes of lung tissues were accentuated in group DY. Conclusion:The mechanism by which dexmedetomidine alleviates VILI may be related to activating alpha2-adrenergic receptors and inhibiting ERK/Na + -K + -ATPase signaling pathway in rats.
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Objective:To evaluate the accuracy of lung recruitment maneuver (LRM) combined with brachial artery peak velocity variation (ΔVp) in predicting fluid responsiveness.Methods:Sixty-four patients of both sexes, aged 18-64 yr, with body mass index 19-26 kg/m 2, of American Society of Anesthesiologists physical status Ⅰor Ⅱ, with New York Heart Association class Ⅰor Ⅱ, scheduled for elective open gastrointestinal surgery under general anesthesia, were enrolled in this study.LRM (positive airway pressure was maintained at 30 cmH 2O for 10 s) and volume loading test were performed in sequence after anesthesia induction.ΔVp was measured by ultrasonography at the beginning of LRM.Mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP) and stroke volume (SV) were recorded before LRM (T 1), during LRM (T 2), before volume expansion (T 3) and after volume expansion (T 4). The changing rate of each index before and after LRM (ΔMAP LRM, ΔHR LRM, ΔCVP LRM, ΔSV LRM) and before and after volume expansion (ΔMAP VE, ΔHR VE, ΔCVP VE, ΔSV VE) were calculated.ΔSV VE≥15% was considered to be a positive response after volume expansion, and patients were divided into response group (≥ 15%, R group) and non-response group (< 15%, NR group). Results:There were 34 cases in R group and 30 cases in NR group.Compared with NR group, MAP at T 2 and SV at T 1, 2 were significantly decreased, ΔMAP LRM, ΔMAP VE, ΔSV LRM and ΔSV VE were increased, and ΔVp was increased in group R ( P<0.05). There was a positive correlation between ΔVp and ΔSV VE ( r=0.829, P<0.05), a negative correlation between ΔSV LRM and ΔSV VE ( r=-0.876, P<0.05), and a negative correlation between ΔVp and ΔSV LRM ( r=-0.819, P<0.05). The area under the receiver operating characteristic curve of LRM combined with ΔVp was 0.808, and the cut-off value was 32.3%, the sensitivity 75.3%, and the specificity 88.2%. Conclusion:LRM combined with ΔVp (≥32.3%) can accurately predict the intraoperative fluid responsiveness in patients.
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Objective To investigte the efficacy of docetaxel combined with androgen deprivation therapy for the treatment of metastatic hormone-sensitive prostate cancer based on Chinese population.Methods A total of 497 patients were enrolled from January 2004 to July 2018 in the Changhai Hospital.459 patients received androgen deprivation therapy alone and 38 patients received androgen deprivation therapy combined with docetaxel.The mean age was (72.1 ± 8.7)years.The median PSA level was 100.0 ng/ml,ranging 42.3-999.0 ng/ml.Patients of clinical T2,T3,T4 stage were 213 (42.9％),160 (32.2％),124(24.9％),respectively.Patients of clinical N0,N1,Nx stage were 319 (64.2％),144 (29.0％),34 (6.8％),respectively.Patients of clinical M0,M1a,M1b,M1c,Mx stage were 100(20.1％),51 (10.3％),332 (66.8％),9 (1.8％),5 (1.0％),respectively.Gleason scores of biopsy showed that 146 (29.4％) patients was ≤7,103(20.7％) was 8 and 248(49.9％)was ≥9.Propensity score matching was used to match the baseline between groups.Caliper value was set at 0.02.SPSS 22 software was used to achieve a 1:1 match between the two groups.There were no statistical difference in the age(P =0.102),PSA (P =0.713),T stage (P =0.113),N stage (P =0.226),M stage (P =0.514),Gleason score (P =0.612),tumor loading(P =0.812) between the two groups.The castration resistance-free rate and cancer specific survival rate of the two groups were compared by log-rank and breslow-wilcoxon test.Furthermore,forest plots were used to display the analysis results of different subgroups such as age,PSA,clinical stage,Gleason score,tumor load,whether patients had received palliative resection,and the differences in castration resistance-free rate were compared between the subgroups with high tumor load.Results The median follow-up time was 22.6 months in the androgen deprivation therapy group and 13.7 months in the combined therapy group.The number of patients with castration resistance in the two groups was 23 and 17,respectively.There were 3 and 6 deaths,respectively.There was no statistically significant difference in the overall progression time to castration resistance between the two groups (10.3 m vs.16.5 m,P ＞ 0.05),and no statistically significant difference in the prostate cancer specific survival rate (21.9 m vs.14.8 m,P ＞ 0.05).When subgroup analysis was performed,it was found that patients in the high-metastasis-volume subgroup who received the combination therapy had a significantly longer castration resistance free lifetime (10.6 m vs.7.2 m,P =0.044),but there was no significant difference in the low-metastasis-volume subgroup (10.5 m vs.12.6 m,P ＞ 0.05).Conclusion Docetaxel combined with androgen deprivation therapy can improve the castration resistance free rate in patients with high metastasis volume,but not in low metastasis volume group.
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Objective:To provide support for the clinical application of quantitative computed tomography (QCT) in the measurement of liver fat content, this study evaluated the intra-observer and inter-observer reproducibility of liver fat content measured by QCT in a population receiving physical examinations.Methods:From April to July 2019, 291 people were consecutively selected who underwent QCT examination in the health management department of Henan Provincial People′s Hospital. There were 214 males (73.5%) and 77 females (26.5%), aged 48.7±11.0. We measured liver fat content by QCT workstation. Three observers (A, B, C) measured their liver fat content independently, then observer A performed re-testing two weeks later. The mean value of the two measurements from observer A was taken as the final result. Measurement data were described by mean±SD. Intra-observer and inter-observer reproducibility were assessed using intra-class correlation coefficients ( ICC). Results:The first measurement result for observer A was 10.46±5.55 and the second measurement for observer A was 10.66±5.59, resulting in a final value of 10.56±5.51. The measurement results of observers B and C were 10.70±5.45 and 10.86±5.77, respectively. The ICC value of liver fat content values measured by the three observers was 0.960 (95% CI: 0.951-0.967, P<0.001) and the ICC value of liver fat content values for the two measurements of observer A was 0.953 (95% CI: 0.941-0.962, P<0.001). The ICC values were>0.75, so reproducibility of results was good. Conclusions:If the measurement method is consistent, the results for liver fat content measured by a conventional CT scanner and QCT workstation will have good reproducibility between and within observers, and will also have certain clinical application prospects.
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Objective@#To evaluate the efficacy of transversus abdominis plane block (TAPB) with different doses of dexmedetomidine mixed with ropivacaine in the pediatric patients undergoing laparoscopic surgery with general anesthesia.@*Methods@#Eighty patients of both sexes, aged 3-6 yr, weighing 10-30 kg, scheduled for elective single-channel laparoscopic appendectomy, were divided into 4 groups (n=20 each) using a random number table method: 0.5 μg/kg dexmedetomidine plus ropivacaine group (group DR1), 1.0 μg/kg dexmedetomidine plus ropivacaine group (group DR2), 1.5 μg/kg dexmedetomidine plus ropivacaine group (group DR3), and ropivacaine group (R group). Bilateral TAPB was performed under ultrasound guidance after the end of anesthesia induction.In group TR, 0.25% ropivacaine 0.5 ml/kg was injected, the 0.5 ml/kg mixture of 0.5, 1.0 and 1.5 μg/kg dexmedetomidine and ropivacaine at a final concentration of 0.25% was injected in DR1, DR2 and DR3 groups.Anesthesia was maintained by intravenously infusing remifentanil and inhaling sevoflurane.Cisatracurium was intermittently injected to maintain muscle relaxation.Ibuprofen was taken orally to maintain postoperative FLACC score <4.The intraoperative consumption of remifentanil, tracheal extubation time, duration of anesthetic recovery room stay, requirement for ibuprofen, and occurrence of opioids- and TAPB-related complications were recorded.@*Results@#There was no significant difference in the intraoperative consumption of remifentanil or tracheal extubation time between four groups (P>0.05). Compared with group R, the requirement for ibuprofen was significantly decreased in DR2 and DR3 groups, the duration of anesthetic recovery room stay was significantly prolonged in group DR3 (P<0.05), and no significant change was found in the requirement for ibuprofen in group DR1 or in the duration of anesthetic recovery room stay in DR1 and DR2 groups (P>0.05). Compared with group DR1, the duration of anesthetic recovery room stay was significantly prolonged, and the requirement for ibuprofen was decreased in group DR3, and the requirement for ibuprofen was significantly decreased (P<0.05), and no significant change was found in the duration of anesthetic recovery room stay in group DR2 (P>0.05). Compared with group DR2, the duration of anesthetic recovery room stay was significantly prolonged (P<0.05), and no significant change was found in the other parameters in group DR3 (P>0.05). No patients developed opioids- or TAPB-related complications.@*Conclusion@#TAPB with 1.0 μg/kg dexmedetomidine mixed with ropivacaine provides good efficacy for the pediatric patients undergoing laparoscopic surgery with general anesthesia.
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Objective To evaluate the efficacy of transversus abdominis plane block (TAPB) with different doses of dexmedetomidine mixed with ropivacaine in the pediatric patients undergoing laparoscopic surgery with general anesthesia.Methods Eighty patients of both sexes,aged 3-6 yr,weighing 10-30kg,scheduled for elective single-channel laparoscopic appendectomy,were divided into 4 groups (n =20each) using a random number table method:0.5 μg/kg dexmedetomidine plus ropivacaine group (group DR1),1.0 μg/kg dexmedetomidine plus ropivacaine group (group DR2),1.5 μg/kg dexmedetomidine plus ropivacaine group (group DR3),and ropivacaine group (R group).Bilateral TAPB was performed under ultrasound guidance after the end of anesthesia induction.In group TR,0.25％ ropivacaine 0.5 ml/kg was injected,the 0.5 ml/kg mixture of 0.5,1.0 and 1.5 μg/kg dexmedetomidine and ropivacaine at a final concentration of 0.25％ was injected in DR1,DR2 and DR3 groups.Anesthesia was maintained by intravenously infusing remifentanil and inhaling sevoflurane.Cisatracurium was intermittently injected to maintain muscle relaxation.Ibuprofen was taken orally to maintain postoperative FLACC score ＜4.The intraoperative consumption of remifentanil,tracheal extubation time,duration of anesthetic recovery room stay,requirement for ibuprofen,and occurrence of opioids-and TAPB-related complications were recorded.Results There was no significant difference in the intraoperative consumption of remifentanil or tracheal extubation time between four groups (P＞0.05).Compared with group R,the requirement for ibuprofen was significantly decreased in DR2 and DR3 groups,the duration of anesthetic recovery room stay was significantly prolonged in group DR3 (P＜0.05),and no significant change was found in the requirement for ibuprofen in group DR1 or in the duration of anesthetic recovery room stay in DR1 and DR2 groups (P＞0.05).Compared with group DR1,the duration of anesthetic recovery room stay was significantly prolonged,and the requirement for ibuprofen was decreased in group DR3,and the requirement for ibuprofen was significantly decreased (P＜0.05),and no significant change was found in the duration of anesthetic recovery room stay in group DR2 (P＞0.05).Compared with group DR2,the duration of anesthetic recovery room stay was significantly prolonged (P＜0.05),and no significant change was found in the other parameters in group DR3 (P＞ 0.05).No patients developed opioids-or TAPB-related complications.Conclusion TAPB with 1.0 μg/kg dexmedetomidine mixed with ropivacaine provides good efficacy for the pediatric patients undergoing laparoscopic surgery with general anesthesia.
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Objective To compare internal jugular vein diameter and brachial artery peak velocity variation (VVp) in predicting fluid responsiveness.Methods Sixty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients,of New York Heart Association I,aged 18-64 yr,scheduled for elective gastrointestinal surgery under general anesthesia,were included in this study.Six percent hydroxyethyl starch 130/0.47 ml/kg was infused at a rate of 0.4 ml · kg-1 · min-1 after induction of anesthesia.The patients with the changing rate of stroke volume variation (ASVV) more than or equal to 15％ were included in responsiveness group and patients with ASVV less than 15％ were included in non-responsiveness group after volume expansion.Immediately after volume expansion and at 3 min after volume expansion,mean arterial pressure,central venous pressure and heart rate were recorded,the maximum diameter of the internal jugular vein at the end of inspiration (IJVmax) and the minimum diameter of the internal jugular vein at end of expiration (IJVmin) and brachial artery peak velocity were measured using an ultrasonic instrument,and the variation of internal jugular vein respiration (VIJV) and VVp were calculated.The receiver operating characteristic curve was used to evaluate the accuracy of IJV IJVmin,VIJV and VVp in predicting fluid responsiveness.Results There were 31 patients in responsiveness group and 29 patients in non-responsiveness group.Compared with non-responsiveness group,mean arterial pressure,central venous pressure,IJVmax and IJVmin were significantly decreased and heart rate,VIJV and VVp were increased immediately after volume expansion in responsiveness group (P＜0.05).The areas under receiver operating characteristic curve (AUC) of IJV IJVmin,VIJV and VVp were 0.753,0.948,0.837 and 0.832,respectively.AUC IJVmax,AUCVIJV and AUCVVp were significantly decreased when compared with AUC IJVmin (P＜0.05).Conclusion The accuracy of IJVmax is higher than that of VVp in predicting intraoperative fluid responsiveness in the patients.
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Objective To introduce the initial application experience of SUTURE (suture-undertent and underside-reposition-enhancement) technique in robotic-assisted radical prostatectomy and discuss its safety and effectiveness.Methods The surgeon has performed 64 cases of Robotic-assisted radical prostatectomy between November 2016 to April 2017.The mean age was (66.6 ± 1.6) years (53-81 years);median PSA was 15.29 ng/ml(1.41-152.53 ng/ml),tumor stage was T1cN0M0-T3bN0M0.The patients were diagnosed by ultrasound-guide prostate biopsy.The number of cores was 6-15,average Gleason score was 7.3 points (6-10 pionts).ECT and MR were used to assess local stage and bone metastasis.The tPSA and urine recovery (urine pad test) was followed-up regularly.SUTURE technique consists of two parts,control the DVC effectively by retain the puboprostatic ligaments and puboprostatic ligaments reconstruction.Result All cases were successfully completed without complication,the average operation time was 95 min (66-150 min);bleeding (106 ± 15) ml(50-300 ml).All the catheters were released 14 days after surgery.Postoperative pathological staging was pT2aN0-pT3bN1,25 cases of capsule invasion,12 cases with seminal vesicle invasion,37 cases with nerve invasion.Average Gleason score was 7.2 points (6-10 points).The median tPSA detected 4 weeks after surgery was 0.047 ng/ml(0.007-12.050 ng/ml).The follow-up time was 1-6 months.The rate of urine control in 1 month and 3 month were 40.8％ (20/49) and 75.8％ (25/33).Conclusions By using SUTURE technique we can control thedorsal vascular complexstrictly,and complete the puboprostatic ligaments reconstruction by stitch it to the anterior vesicourethral.The SUTRUE is a safe and effective systematic DVC controlling technique,and the early urinary control rate is satisfactory.
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Objective To investigate the effect of compound polyethylene glycol electrolyte powder (SF-PEG) and Magnesium Sulfate (MgSO4) on intestinal tract preparation in patients with constipation. Methods 135 cases of constipation patients who underwent colonoscopy were selected. They were divided into A, B and C groups, each with 45 cases.Group A and group B received oral SF-PEG and 219.2 g (2 000 ml) at 5:00 to 7:00. Group A take 50% MgSO450 ml at 9:00, and then took 250 ml warm water.Group B received the same dose of MgSO4 at 7:00. The two groups were examined by colonoscopy at 11:00. Group C received oral compound SF-PEG 219.2 g (2 000 ml) at 10:00 to 12:00, and then took 50% MgSO450 ml at 14:00, received colonoscopy at 16:00. According to the Boston bowel preparation scale (BBPS) score and parallel intraluminal bubble score. Determine the duration of bowel preparation process,and tolerance and adverse effects were recorded during bowel preparation. Results All patients completed bowel preparation and underwent a colonoscopy successfully. The scores of group A in BBPS were significantly higher than those in group B and group C (P < 0.05). In group A and group B, the score of parallel intraluminal bubble was lower than C, which was statistically significant (P < 0.05). The intestinal preparation time of A and B was less than that of group C, which was statistically significant (P < 0.05), and the tolerance of patients was higher in group A and group B than that in group C (P < 0.05). In adverse reactions, group A and group B were lower than those in group C (P < 0.05). Conclusions When taking the time (5:00 to 7:00), intermittent polyethylene glycol electrolyte powder and Magnesium Sulfate can shorten the bowel preparation time and improve the quality of bowel preparation in patients with constipation.