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Stroke is the second leading cause of death worldwide,and oxidative stress plays a crucial role.Celastrol exhibits strong antioxidant properties in several diseases;however,whether it can affect oxidation in cerebral ischemic-reperfusion injury(CIRI)remains unclear.This study aimed to determine whether celastrol could reduce oxidative damage during CIRI and to elucidate the underlying mechanisms.Here,we found that celastrol attenuated oxidative injury in CIRI by upregulating nuclear factor E2-related factor 2(Nrf2).Using alkynyl-tagged celastrol and liquid chromatography-tandem mass spectrometry,we showed that celastrol directly bound to neuronally expressed developmentally downregulated 4(Nedd4)and then released Nrf2 from Nedd4 in astrocytes.Nedd4 promoted the degradation of Nrf2 through K48-linked ubiquitination and thus contributed to astrocytic reactive oxygen species production in CIRI,which was significantly blocked by celastrol.Furthermore,by inhibiting oxidative stress and astrocyte activation,celastrol effectively rescued neurons from axon damage and apoptosis.Our study uncovered Nedd4 as a direct target of celastrol,and that celastrol exerts an antioxidative effect on as-trocytes by inhibiting the interaction between Nedd4 and Nrf2 and reducing Nrf2 degradation in CIRI.
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Objective:To evaluate the risk and prognostic factors of brain metastasis (BM) after prophylactic cranial irradiation (PCI) in limited stage small cell lung cancer (LS-SCLC) patients with complete and partial remission (CR/PR) after radiochemotherapy.Methods:Baseline data of 550 patients with LS-SCLC who obtained CR/PR after chemoradiotherapy and received PCI in Zhejiang Cancer Hospital between 2002 and 2017 were collected. The risk of BM and clinical prognosis were retrospectively analyzed. The survival analysis was performed by Kaplan-Meier method. Multivariate prognostic analysis was conducted byCox models.Results:The overall BM rate after PCI was 15.6%(86/550), with 9%(4/43), 13%(7/52), and 16.5%(75/455) for stage Ⅰ, Ⅱ and Ⅲ patients, respectively. The median overall survival (OS) for the entire cohort was 27.9 months, and the 5-year OS rate was 31.0%. The OS was 24.9 and 30.2 months for patients with or without BM, and the 5-year OS rates were 8.9% and 36.1%( P<0.001). BM was an independent factor of OS ( P<0.001). Clinical staging remained the influencing factor of OS and BM-free survival ( P<0.001, P=0.027). Having tumors of ≥5 cm in diameter significantly increased the risk of BM ( P=0.034) rather than the OS ( P=0.182). The median OS of patients aged<60 years was significantly longer than those aged ≥60 years (34.9 months vs. 24.6 months, P=0.001). The median OS of patients irradiated with 2 times/d was 29.8 months, significantly longer than 24.5 months of those irradiated with 1 time/d ( P=0.013). Age, sex, radiotherapy fraction and efficacy of radiochemotherapy (CR/PR) were not associated with the incidence rate of BM (all P>0.05). Conclusions:SCLC patients with tumors of ≥5 cm in diameter may have a higher risk of developing BM after PCI. Patients aged<60 years achieve better OS compared with their counterparts aged ≥60 years.
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Radiation-induced lung injury (RILI) is a common complication in thoracic cancer patients through radiotherapy, which can be divided into the early-stage radiation-induced pneumonitis (RP) and late-stage radiation-induced lung fibrosis (RILF). At present, glucocorticoids are mainly adopted in the clinical treatment of RP. However, there has been no effective medical treatment for RILF. RILF patients will eventually die from respiratory failure. The exact mechanism of RILI remains unclear. Current studies have proposed that its possible pathogenesis might consist of genetic heterogeneity, oxidative stress and cell damage. In this review, studies related to the pathogenesis of RILI were summarized.
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With the advancement of imaging diagnosis and the development of modern radiotherapy, the survival of cancer patients has been prolonged and the incidence rate of brain metastases (BM) has been significantly increased. The quality of life of patients and potential radiotherapy-induced neurocognitive impairment have gradually captivated widespread attention. Whole brain radiotherapy (WBRT) is one of the common local therapies for BM patients. However, the application of WBRT is controversial because it may lead to neurocognitive impairment. The incidence of metastatic tumors in hippocampus and radiation-induced neurocognitive impairment can accelerate the implementation of hippocampal-avoidance WBRT (HA-WBRT). In this article, the feasibility of HA-WBRT was discussed and research progress in recent years was reviewed.
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Objective:To analyze the feasibility of hippocampal-avoidance (HA) prophylactic cranial irradiation (PCI) in small cell lung cancer patients (SCLC)(limited stage) after chemotherapy and thoracic radiation.Methods:From June 2016 to March 2019, 40 eligible SCLC patients were recruited and randomly divided into the routine PCI ( n=22) and hippocampal-avoidance PCI (HA-PCI) groups ( n=18). The HA zone was contoured according to the criteria of RTOG 0933. Volumetric-modulated arc therapy (VMAT) was adopted in the HA-PCI group. After radiotherapy, Hopkins verbal learning test (HVLT) and MRI were performed. Results:The average hippocampus volume was (4.01±1.57) cm 3, the average HA volume was (20.13±4.14) cm 3, HA D 100% was (7.19±0.38) Gy and HA D max was (14.38±1.18) Gy. During HVLT, 1-month-after-PCI vs. before-PCI (trial3, trial4, learning, percent retained), 1-month-after-PCI vs. after-PCI (trial3, learning), HA-PCI cohort showed advantages over PCI in HVLT scores. The average follow-up time was (17.00±8.47) months. Two patients with brain metastases which were out of the HAZ received routine PCI. Conclusions:PCI using VMAT technology to protect hippocampus is feasible in dosimetry. The test results indicate that the protective effect of hippocampus protection on memory is worthy of further promotion in clinical practice.
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The emergence of immune checkpoint inhibitors (ICI) provides a novel method for the treatment of non-small cell lung cancer (NSCLC). However, the limitation of ICI alone prompts clinicians to explore the feasibility of radiotherapy combined with ICI. Recent studies on this combined therapy have preliminarily revealed its significant prospects for changing the treatment system of NSCLC. From the perspective of the mechanism of combined therapy, this study reviewed the basic research on this combined therapy and the clinical progress on different radiotherapy combined with ICI.
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Objective@#To compare the overall survival (OS), progression-free survival (PFS) and brain metastasis free survival (BMFS) between the chemo-radiotherapy and surgical treatment for patients with limited stage small cell lung cancer (LS-SCLC).@*Methods@#Clinical data of 69 patients diagnosed with LS-SCLC undergoing surgery in Zhejiang Cancer Hospital between 2000 and 2016 were collected. According to T, N stage, treatment duration, age, gender and whether or not prophylactic cranial irradiation (PCI), 69 patients of 503 LS-SCLC patients who underwent standard radiochemotherapy were assigned into the radiochemotherapy group by using the pair-matched case-control method.@*Results@#Among 138 patients, 69 cases were allocated into the surgery group (24 cases of stage Ⅰ, 14 cases of stage Ⅱ and 31 cases of stage Ⅲ) and 69 cases in the radiochemotherapy group (24 cases of stage Ⅰ, 14 cases of stage Ⅱ and 31 cases of stage Ⅲ). The median OS time was 37.1 months (95%CI: 24.1-50.2 months) in surgery group and 45.0 months (95%CI: 15.8-74.2 months) in the radiochemotherapy group. The 2-and 5-year OS rates were 60% and 45% in the surgery group, and 64% and 45% in the radiochemotherapy group (P=0.846). The median PFS time was 27.1 months (95%CI: 0.00-60.3 months) in the surgery group and 36.2 months (95%CI: 20.9-51.4 months) in the radiochemotherapy group. The 2-and 5-year PFS rates were 52%, and 38% in the surgery group, and 56% and 40% in the chemo-radiotherapy group (P=0.610). The 2-and 5-year BMFS rates were 81% and 76% in the surgery group, and 84% and 80% in the radiochemotherapy group (P=0.774). The 5-year OS rate (62% vs. 40%, P=0.038) and 5-year PFS rate (80% vs.40%, P=0.048) for patients with stage Ⅰ LS-SCLC in the surgery group were significantly higher than those in the radiochemotherapy group. However, the 5-year BMFS rate in patients with stage Ⅰ LS-SCLC did not significantly differ between two groups (92% vs.95%, P=0.816). The 5-year OS rate (41% vs.51%, P=0.946), 5-year PFS rate (65% vs.42%, P=0.280) and 5-year BMFS rate (75% vs.78%, P=0.720) for stage Ⅱ SCLC did not significantly differ between two groups. As for stage Ⅲ SCLC patients, the OS rate (25% vs.48%, P=0.220), 5-year PFS rate (28% vs.36%, P=0.333) and 5-year BMFS rate (76% vs. 74%, P=0.84) did not significantly differ between two groups.@*Conclusions@#Surgical treatment can bring survival benefits to patients with stage Ⅰ LS-SCLC. The survival prognosis of stage Ⅱ patients is equivalent between two groups. Patients with stage Ⅲ LS-SCLC receiving radiochemotherapy obtain better survival trend compared with those undergoing surgery. The conclusion remains to be validated by studies with larger sample size or prospective investigations.
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Objective To evaluate the accuracy of variation of the end-tidal pressure of carbon dioxide (△PETCO2) in predicting the fluid responsiveness in patients undergoing resection of gastrointestinal tumor.Methods Forty-six patients of both sexes,aged 40-64 yr,with body mass index of 20-24 kg/m2,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,undergoing elective resection of gastrointestinal tumor with general anesthesia,were enrolled in the study.When the change in mean arterial pressure was less than 10％ within 5 min after anesthesia induction,250 ml Ringer's solution was rapidly infused over 10 min via the peripheral vein.Increase in cardiac index after volume expansion ≥ 15％ was considered to be a positive response.The receiver operating characteristic curve for △PETCO2 in determining fluid responsiveness was drawn.Results The results of receiver operating characteristic curve analysis showed that the area under the curve for △PETCO2 in determining fluid responsiveness (95％ confidence interval) was 0.826 (0.730-0.942,P＜0.05),the critical value 21.9％,sensitivity 76.5％,specificity 90.9％.Conclusion △PETCO2 can accurately predict the fluid responsiveness in patients undergoing resection of gastrointestinal tumor.
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Objective In view of the controversy over radiotherapy target volume for patients with limited-stage small cell lung cancer ( SCLC), a prospective randomized controlled trial was conducted to compare the impact of different radiotherapy target volumes on prognosis. Methods After 2 cycles of EP chemotherapy,patients without progressive disease were randomly assigned to receive thoracic radiotherapy (TRT) to either the post-or pre-chemotherapy primary tumour extent as study arm or control. Involved field radiotherapy (IFRT) to the entire metastatic lymph node regions was applied for both arms. TRT consisted of 45 Gy/30Fx/19 d administered concurrently with cycle 3 chemotherapy. Prophylactic cranial irradiation was administered to patients achieved complete or partial remission. Kaplan-Meier method was used for survival analysis. Results Between June 2002 and December 2017,159 and 150 patients were randomly assigned to study arm and control respectively. The 1-,2-,and 5-year local/regional control rates were 79. 4%,61. 5% and 60. 1% respectively in the study arm versus 79. 8%,66. 5%,and 57. 3% in the control arm (P=0. 73). The median OS time was 22. 1 months in the study arm (95%CI,18. 2-26. 0 months) and 26. 9 months (95%CI,23. 5-30. 3 months) in the control arm,the 1-,3-,5-,and 7-year OS rates were 81. 1%,31. 6%, 23. 9% and 22. 2% respectively in the study arm versus 85. 3%,36. 6%,26. 1% and 20. 0% in the control arm (P=0. 51).Grade 2-3 acute esophagitis was developed in 32. 9% and 43. 2% of patients respectively in study arm and control arm (P=0. 01),while grade 2-3 pulmonary fibrosis was observed in 2. 0% and 10. 9% of patients ( P= 0. 01 ) respectively. Conclusions For patients with limited-stage SCLC who received induction chemotherapy,thoracic radiotherapy can be limited to post-chemotherapy tumour extent and IFRT can be routinely applied.
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The incidence of small cell lung cancer ( SCLC) is relatively low, which approximately accounts for 13％-20％ of all types of lung cancers. SCLC is characterized by high-degree malignancy and high metastasis and recurrence rates within a short period of time. Upon the confirmed diagnosis, limited-stage SCLC approximately accounted for 30％ of SCLC and merely 5％ of these patients were eligible for surgery. Over half of the patients who obtained complete remission after chemoradiotherapy presented with brain metastases. The postoperative incidence of brain metastases in patients with stageⅠ,ⅡandⅢSCLC was 6％-14％,13％-38％ and 11％-36％, respectively. Prophylactic cranial irradiation ( PCI) can enhance the overall survival rate of patients with complete remission after chemoradiotherapy and reduce the incidence of brain metastasis, which is a pivotal part of comprehensive treatment of limited-stage SCLC. However, the application of PCI remains controversial in clinical practice and the clinical efficacy for patients with surgically resected SCLC significantly varies. In this article, literature review was conducted and the research progress in this field was summarized.
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Objective To evaluate the clinical efficacy of prophylactic cranial irradiation (PCI) in the treatment of surgically resected small cell lung cancer (SCLC).Methods Clinical data of SCLC patients undergoing radical resection surgery in Zhejiang Cancer Hospital from 2003 to 2015 were retrospectively analyzed.According to the treatment modality,all patients were allocated into the PCI and non-PCI groups.A total of 52 patients were finally included,including 19 patients in the PCI group (5 cases of stage Ⅰ,5 stage Ⅱ and 9 stage Ⅲ) and 33 in the non-PCI group (12 cases of stage Ⅰ,5 stage Ⅱ and 16 stage Ⅲ).Kaplan-Meier method was utilized for survival analysis.Cox proportional hazards model was adopted to analyze clinical prognosis.Results The median survival time was 32.9 months in the PCI group,and 20.4 months in the non-PCI group.The 2-year overall survival rate was 72％ in the PCI group,significantly higher than 38％ in the non-PCI group (P=0.023).The median brain metastasis-free survival (BMFS) was 32.5 months in the PCI group,and 17.1 months in the non-PCI group.In the PCI group,the 2-year BMFS rate was 89％,significantly better than 53％ in the non-PCI group (P=0.026).Subgroup analysis demonstrated that PCI could confer survival benefit to patients with p-stage Ⅲ (p=0.031) rather than p-stage Ⅰ (P=0.924) and Ⅱ (P=0.094) counterparts.Multivariate analysis revealed that PCI (HR=0.330,P=0.041) was an independent prognostic factor of the overall survival.Conclusions PCI can reduce thr risk of brain metastasis rate and improve the overall survival of patients with surgically resected SCLC.
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Objective To evaluate the clinical efficacy between stereotactic body radiotherapy (SBRT) and surgical treatment for stage Ⅰ-Ⅱ non-small cell lung cancer (NSCLC).Methods Clinical data of 120 patients with early-stage NSCLC who underwent SBRT or surgical treatment in Zhejiang Cancer Hospital from 2012 to 2015 were retrospectively analyzed.Propensity score matching was carried out between two groups.Sixty eligible patients were enrolled in each group.In the SBRT group,the 80％ isodose line covered 95％ of the planning target volume,and the 100％ isodose line covered 100％ of the internal gross tumor volume.The fractional dose was 5-15 Gy and the median biologically equivalent dose was 100 Gy (range:57.6-150.0 Gy).In the operation group,32 patients underwent video-assisted thoracoscopic lobectomy and 9 patients underwent wedge resection or segmentectomy.Results All patients successfully completed corresponding treatment and were followed up.The median follow-up was 32.3 months (range:8.6-68.4 months).In the operation group,3 patients died from infection within postoperative 90 d,whereas no case died in the SBRT group (P=0.079).In the SBRT group,3 patients died of other factors besides tumor (cerebral infarction,heart disease,etc.) during follow-up.Local-regional recurrence occurred in 12 patients including 5 cases in the operation group and 7 in the SBRT group (P=0.543).In the operation group,11 patients experienced distant metastases with a median disease-free survival (DFS) of 33.5 months.In the SBRT group,6 patients had distant metastases and the median DFS was 38.4 months (P=0.835,P=0.178).In the SBRT group,the 1-and 3-year overall survival rates were 93％ and 83％,and 95％ and 83％ in the operation group (P=0.993).Conclusions The 1-and 3-year overall survival rates and local control rate do not significantly differ between SBRT and operation for patients with early-stage NSCLC.
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Objective To analyze the exposed dose of hippocampus(HC)of T3,T4nasopharyngeal carcinoma patients treated with intensity modulated radiotherapy(IMRT). Methods The bilateral HCs were delineated and were divided into head(HH),body(HB)and tail(HT)for 62 nasopharyngeal carcinoma patients treated with IMRT.The dose parameters of HC were then analyzed. Results The mean dose of left and right HC was(1 127±704)cGy,(1 173±762)cGy. The mean dose of left HH,HB and HT was(1 732±1029)cGy,(820±632)cGy,(423±366)cGy(P=0.000);while the mean dose of right HH, HB and HT was(1 985±1101)cGy,(837±531)cGy,(432±343)cGy(P=0.000).The exposed dose and the volume exposed in different dose of HH were obviously higher than those of HB and HT.The dose parameters of HH,HB and HT decreased in turn. The involvement of sphenoid sinus,ethmoid sinus and cavernous sinus correlated with high exposed dose of HC. Conclusions The exposed dose of HH,HB and HT was different in nasopharyngeal carcinoma patients treated with IMRT.The exposed dose of HH was the highest,which should be emphasized especially. The involvement of sphenoid sinus,ethmoid sinus and cavernous sinus suggest high exposed dose of HC.
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@#Objective To observe the effect of Kinesio Taping with lattice shapes on pregnancy-related low back pain (PLBP). Methods From March, 2017 to April, 2018, 56 patients with PLBP were randomly divided into the control group (n = 28) and experimental group (n = 28). Both groups received the core stability training, while the experimental group accepted Kinesio Taping with lattice shapes additionally. They were assessed with Visual Analogue Scale (VAS), Roland-Morris Dysfunction Questionnaire (RMDQ), range of lumbar activity and torso angle before, three days and two weeks after treatment. Results The range of lumbar activity improved significantly in both groups (t > 6.327, P < 0.01) three days after treatment, while the scores of VAS and RMDQ, and the torso angle improved significantly in the experimental group (t > 4.862, P < 0.001). The scores of VAS and RMDQ, the range of lumbar activity, and the torso angle improved significantly in both groups two weeks after treatment (P < 0.001), and improved more in the experimental group than in the control group (P < 0.05). Conclusion Kinesio Taping with lattice shapes combined with core stability training can further reduce the lower back pain and improve the function for the PLBP patients.
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Objective To evaluate the effects of lung-protective ventilation on the cerebral oxygen metabolism and postoperative cognitive function in elderly patients requiring one-lung ventilation (OLV).Methods Sixty patients of both sexes,aged 65-80 yr,weighing 45-75 kg,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,scheduled for elective radical resection for esophageal cancer performed via video-assisted thoracoscope with general aneshesia,were divided into 2 groups (n =30 each)using a random number table:volume-controlled ventilation group (group VCV) and protective ventilation group (group PV).In group VCV,the tidal volume (VT) was set at 10 ml/kg during two-lung ventilation (TLV) and at 7 ml/kg during OLV.In group PV,the VT was set at 7 ml/kg during TLV and at 5 ml/kg during OLV with positive end-expiratory pressure of 5 cmH2O,and lung recruitment maneuver was performed every 45 min with inspiratory pressure at 15,20 and 25 cmH2O,PEEP 5 cmH2O,3 breaths per pressure,5 s/breath.Before induction of anesthesia (T1),at 10 min of TLV (T2),at 30 min of OLV (T3) and at 15 min after restoration of TLV (T4),blood samples were taken from the radial artery and jugular bulb for blood gas analysis,and pH value,arterial oxygen partial pressure (PaO2),arterial carbon dioxide partial pressure (PaCO2),arterial oxygen saturation (SaO2) and jugular venous oxygen saturation (SjvO2) were recorded.Oxygenation index (OI),intrapulmonary shunt (Qs/Qt),arteriovenous blood O2 content difference (Da-jvO2) and cerebral O2 extraction rate (CERO2) were calculated at the same time.Cognitive function was assessed using Mini-Mental State Examination at 7 days and 1 month after operation,and the development of postoperative cognitive dysfunction was recorded.Results PaO2,DajvO2,CERO2 and Qs/Qt were significantly higher and SjvO2 and OI were lower at T2-4 than at T1 in two groups (P＜0.05).PaO2,SjvO2 and OI were significantly lower and Qs/Qt and CERO2 were higher at T3 than at T2,and Da-jvO2 was higher at T3-4 than at T2 in two groups (P＜0.05).Compared with group VCV,PaO2,PaCO2,SjvO2 and OI were significantly increased and Qs/Qt,Da-jvO2 and CERO2 were decreased at T3,the Mini-Mental State Examination scores were increased on postoperative day 7,and the incidence of postoperative cognitive dysfunction was decreased in group PV (P＜O.05).Conclusion Lungprotective ventilation is helpful in improving postoperative brain function of elderly patients requiring OLV.
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Objective To investigate the effects of hyperfractionated radiotherapy versus hypofractionated radiotherapy combined with concurrent chemotherapy on the prognosis of limited-stage small-cell lung cancer (SCLC).Methods A total of 188 patients with limited-stage SCLC were enrolled in this study and divided into hyperfractionated group (n=92) and hypofractionated group (n=96).The hyperfractionated group received thoracic radiotherapy at 45 Gy in 30 fractions twice a day, while the hypofractionated group received 55 Gy in 22 fractions once a day.The Kaplan-Meier method was used to calculate survival rates, and the Cox model was used for multivariate prognostic analysis.Results There were not significant differences in 1-, 2-, and 5-year progression-free survival (PFS) rates and 1-, 2-, and 5-year overall survival (OS) rates between the hyperfractionated group and the hypofractionated group (82% vs.85%, 61% vs.69%, 59% vs.69%, P=0.27;85% vs.77%, 41% vs.34%, 27% vs.27%, P=0.37).The multivariate analysis showed that the time from the initiation of chemotherapy to the initiation of thoracic radiotherapy ≤43 days was favorable prognostic factor for PFS (P=0.005).The time from the initiation of chemotherapy to the end of thoracic radiotherapy ≤63 days and prophylactic cranial irradiation were favorable prognostic factors for OS (P=0.044;P=0.000).There were significant differences in incidence rates of grade 2 and 3 acute radiation esophagitis between the two groups (28% vs.16%, 9% vs.2%, P=0.009).Conclusions Both hyperfractionated radiotherapy and hypofractionated radiotherapy combined with chemotherapy can improve the PFS and OS of patients with limited-stage SCLC.The time from the initiation of chemotherapy to the initiation of thoracic radiotherapy ≤43 days and the time from the initiation of chemotherapy to the end of thoracic radiotherapy ≤63 days are favorable prognostic factors for PFS and OS, respectively.However, the hyperfractionated group has significantly higher incidence rates of grade 2 and 3 acute radiation esophagitis than the hypofractionated group.
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Objective To evaluate the effect of lung protective ventilation strategy on inflammatory responses in brain tissues of elderly patients requiring one-lung ventilation (OLV) during radical resection for esophagus cancer.Methods Sixty patients of both sexes,aged 65-80 yr,weighing 45-75 kg,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,scheduled for elective radical resection for esophageal cancer,were divided into volume-controlled ventilation (VCV) group (n =30) and VCV plus protective ventilation strategy group (PV group,n =30) using a random number table.In group VCV,the tidal volume was set at 10 ml/kg during two-lung ventilation (TLV) and at 7 ml/kg during OLV with inspiratory/expiratory ratio 1:2.In group PV,the tidal volume was set at 7 ml/kg during TLV and at 5 ml/kg during OLV with inspiratory/expiratory ratio 1:2 and positive end-expiratory pressure 5 cmH2O,and lung recruitment maneuver was performed every 45 min.End-tidal pressure of carbon dioxide was maintained at 35-45 mmHg,and bispectral index value at 40-60 in both groups.Before induction of anesthesia (T1),at 10 min of TLV (T2),at 30 min of OLV (T3),at 15 min after restoration of TLV (T4) and at 24 h after operation (T5),jugular bulb venous blood samples were taken for determination of serum glial fibrillary acid protein,tumor necrosis factor-α and interleukin-6 concentrations by enzyme-linked immunosorbent assay.The cognitive function was assessed using Mini-Mental State Examination before operation (T0),at T5 and at 3 and 7 days after operation (T6,7).The occurrence of postoperative delirium was recorded.Results Compared with group VCV,the serum concentrations of tumor necrosis factor-α,interleukin-6 and glial fibrillary acid protein were significantly decreased at T3-5,Mini-Mental State Examination scores were increased at T6,7,and the incidence of postoperative delirium was decreased in group PV (P＜0.05).Conclusion The mechanism by which lung protective ventilation strategy decreases the development of postoperative cerebral dysfunction is related to reduction of inflammatory responses in brain tissues of elderly patients requiring OLV during radical resection for esophagus cancer.
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Objective To evaluate the lung-protective effect of lung-protective ventilation (LPV) combined with ventilatory mode pressure-controlled ventilation-volume guaranteed (PCV-VG) in elderly patients undergoing one-lung ventilation (OLV).Methods Eighty American Society of Anesthesiologists physical status Ⅰ-Ⅲ patients,aged 65-80 yr,with body mass index of 15-28 kg/m2,scheduled for elective radical resection for esophageal cancer performed via video-assisted thoracoscope,were divided into 4 groups (n=20 each) using a random number table:control group (group C),PCV-VG group,LPV group and LPV combined with PCV-VG group (group LPV+PCV-VG).At 20 min after changing the body position during two-lung ventilation (T1),30 min of OLV (T2) and 20 min after restoration of two-lung ventilation (T3),blood samples were collected from the radial artery for blood gas analysis and for determination of peak airway pressure (Ppeak),mean airway pressure (P) and dynamic lung compliance (Cdyn).Alveolar-arterial oxygen gradient,intrapulmonary shunt (Qs/Qt),dead space fraction (Vd/VT) and respiratory index were calculated at T2.Blood samples were collected from the radial artery before induction of anesthesia and at the end of operation for determination of plasma neutrophil elastase (NE) concentrations by enzyme-linked immunosorbent assay.The Clinical Pulmonary Infection Score (CPIS) was assessed at 1 and 7 days after operation,and the development of pulmonary complications such as respiratory failure,pulmonary atelectasis and pulmonary infection was recorded within 7 days after operation.Results Compared with group C,Ppeak was significantly decreased,and P was increased in group PCV-VG,Ppeak and PaCO2 were significantly increased and pH value,Vd/VT and Qs/Qt were decreased in group LPV,Ppeak,Vd/VT,Qs/Qt,pH value and postoperative CPIS were significantly decreased,and P Cdyn and PaO2 were increased in group LPV+PCV-VG,and the NE concentration at the end of operation was significantly decreased in PCV-VG,LPV and LPV+PCV-VG groups (P＜0.05).Compared with group PCV-VG,P Cdyn and PaO2 were significantly increased,and pH value,Qs/Qt,NE concentration at the end of operation and CPIS were decreased in group LPV+PCV-VG (P＜0.05).Compared with group LPV,Ppeak,Qs/Qt,NE concentration at the end of operation and CPIS were significantly decreased,and Cdyn was increased in group LPV+PCV-VG (P＜0.05).Pulmonary complications such as respiratory failure,pulmonary atelectasis and pulmonary infection were not observed after operation in the four groups.Conclusion LPV combined with PCV-VG can optimize the lung-protective effect in elderly patients undergoing OLV.
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Objective To compare the dosimetric differences in heart and lung among three radiotherapy techniques in the treatment of thoracic esophageal cancer. Methods A total of 15 thoracic esophageal cancer patients treated in Zhejiang Cancer Hospital during the period of January 2015 to February 2016 were enrolled in this retrospective dosimetric study. Three radiotherapy treatment plans, including intensity-modulated radiotherapy ( IMRT) , volumetric intensity modulated arc therapy ( VMAT) with Raystation 4. 0v TPS, and tomotherapy (TOMO) plans with TomoTTM v2. 0. 5 TPS were generated for each patient with a prescribed dose of 60 Gy at 2 Gy per fraction. Dosimetric differences in planning target volume ( PTV) , heart, cardiac subunits and lung were compared. Results The mean volumes of PTV, heart and lung were (399 ±355), (671 ±274) and (3907 ±1717)cm3, respectively. Compared with VMAT and IMRT, TOMO reduced the maximum dose of PTV, heart, left atrium and lung ( H=10. 889, 7. 433, 12. 080, 11. 401, P <0. 05). No difference was observed in conformity or homogeneity among these three plans. Conclusions TOMO reduced the maximum dose to PTV, heart, left atrium and lung compared with VMAT and IMRT, However, no difference in conformity and homogeneity was observed. The impact of dosimetric advantage of TOMO needs further verification due to the interaction between heart and lung for thoracic esophageal cancer patients.
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Objective Resveratrol can improve nonalcoholic fatty liver disease , but its action mechanisms remain unclear . This study aimed to investigate the protective effect of resveratrol against the free fatty acid ( FFA)-induced apoptosis of human hepatic L02 cells and its possible mechanisms . Methods Human hepatic L02 cells were incubated with FFA and resveratrol for 24 hours.The prepared cells were divided into a blank control , an FFA ( 2 mmol/L) , and a resveratrol group ( 50 μmol/L resveratrol +2 mmol L/FFA).After treatment, we measured the triglyceride (TG), glutathi-one (GSH), and malonaldchyde (MDA) contents and caspase3 ac-tivity in the hepatocytes , determined the apoptosis of the cells by flow cytometry , and detected the protein expression of silent information regulator 1 (SIRT1) by Western blot as well as the mRNA expressions of catalase (CAT), Mn superoxide dismucase (MnSOD), Bcl-2, and Bax by qRT-PCR. Results The TG content and caspase 3 activity in the hepatocytes were significantly increased in the FFA ([3518.±64.2] μmol/L and [5.97 ±0.78] U/g) and the resveratrol group ([201.1 ±60.1] μmol/L and [3.60 ±0.73] U/g) as compared with those of the blank control ([40.2 ±7.4] μmol/L and [2.56 ±0.49] U/g) (both P<0.05), but the caspase3 ac-tivity was markedly decreased in the resveratrol group in comparison with that of the FFA group (P<0.05).Both early and late apop-tosis rates of the hepatocytes were remarkably higher in the FFA ([6.75 ±0.81]%and [8.52 ±0.54]%) and the resveratrol group ([4.94 ±0.44]%and [6.52 ±0.61]%) than those in the blank control ([3.38 ±0.33]% and [2.72 ±0.19]%) ( both P<0.05), with statistically significant differences between the former two groups (P<0.05).The resveratrol group showed significant differences in the GSH content ([100.2 ±8.8] nmol/g), the MDA level ([2.36 ±0.82] mg/g), and the relative expression of SIRT1 (0.84 ±0.04) from the FFA group ([73.8 ±13.1] nmol/g, [3.77 ±0.92] mg/g, and 0.61 ±0.07) and the control ([113.7 ±13.8] nmol/g, [1.85 ±0.41] mg/g, and 0.90 ±0.02) (all P<0.05).The resveratrol group also exhibited statistically significant differences in the relative expressions of the MnSOD , CAT, and Bax genes from the FFA and control groups (P<0.05). Conclusion Resveratrol attenuates FFA-induced apoptosis of human hepatic L 02 cells by activating SIRT1 and reducing the oxidative stress of hepatocytes .