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Objective:To investigate the relationship between CD8 +FoxP3 +CD25 + T cell subsets and the therapeutic effect of programmed death receptor 1 (PD-1) inhibitor pembrolizumab in treatment of uterine cervical cancer. Methods:The data of 105 patients with uterine cervical cancer who received pemblizumab therapy based on chemotherapy in the First Hospital of Qinhuangdao from January 2018 to January 2020 were retrospectively analyzed. Flow cytometry was used to detect the ratio of CD8 +FoxP3 +CD25 + T cell in peripheral blood of patients. The efficacy and safety were analyzed. According to the efficacy, all patients were divided into remission group (complete remission + partial remission) and non-remission group (stable disease + progressive disease). The clinical characteristics and CD8 +FoxP3 +CD25 + T cell ratio of the two groups were compared. Multivariate logistic regression model was used to analyze the influencing factors for the efficacy. The efficacy of CD8 +FoxP3 +CD25 + T cell ratio predicting the therapeutic effect of patients was analyzed by using receiver operating characteristic (ROC) curve. Results:The objective remission rate of all patients was 17.14% (18/105), and the incidence of adverse reaction was 39.05% (41/105). The proportion of patients with a family history of cervical cancer in the remission group was lower than that than in the non-remission group [5.56% (1/18) vs. 34.48% (30/87)], and the difference was statistically significant ( χ2=6.00, P=0.014). The proportion of CD8 +FoxP3 +CD25 + T cell of 105 patients before and after treatment was (0.83±0.21)% and (0.77±0.10)%, respectively; the proportion of CD8 +FoxP3 +CD25 + T cell before and after treatment in the remission group was (0.55±0.26)%, (0.31±0.12)%, respectively; the proportion of CD8 +FoxP3 +CD25 + T cell before and after treatment in the non-remission group was (0.89±0.30)%, (0.87±0.28)%, respectively. The proportion of CD8 +FoxP3 +CD25 + T cell after treatment in the remission group was lower than that before treatment ( P < 0.05); there was no statistically significant difference in the proportion of CD8 +FoxP3 +CD25 + T cell before and after treatment in the non-remission group ( P>0.05). The proportion of CD8 +FoxP3 +CD25 + T cell before and after treatment in the non-remission group was higher than that in the remission group (all P<0.001). The proportion of CD8 +FoxP3 +CD25 + T cell higher than the mean value of both groups before treatment and the proportion of CD8 +FoxP3 +CD25 + T cell higher than the mean value of both groups after treatment were independent risk factor of disease remission ( OR=2.542, 95% CI 1.649-3.918, P<0.001; OR=2.936, 95% CI 2.154-4.002, P<0.001). ROC curve analysis showed that the area under the curve of CD8 +FoxP3 +CD25 + T cell ratio predicting the disease remission before treatment was 0.720, and its best cut-off value was 0.77%, the senfitivity was 77.78%, the specificity was 70.11%. Conclusions:Early detection of CD8 +FoxP3 +CD25 + T cell ratio helps to predict the effect of PD-1 inhibitor pembrolizumab therapy for uterine cervical cancer.
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Objective:To investigate the clinical effect of programmed death receptor-1 (PD-1)/programmed death receptor ligand-1 (PD-L1) immunotherapy combined with concurrent radiotherapy and chemotherapy in the treatment of locally advanced cervical cancer (LACC).Methods:From November 2018 to October 2019, 51 LACC patients in Qinhuangdao First Hospital who received anti-PD-1/PD-L1 immunotherapy (pembrolizumab) combined with concurrent radiotherapy and chemotherapy [intensity modulated radiotherapy (IMRT)+ TP (taxol+ carboplatin) chemotherapy] were selected as the observation group. 51 LACC patients who received concurrent chemotherapy and radiotherapy were selected as the control group. The objective remission rate, disease control rate, tumor markers [squamous cell carcinoma antigen (SCCAg), soluble cytokeratin 19 fragment (CYFRA21-1), and carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125)], proliferation and apoptosis indicators [survivin (Survivin), B-cell lymphoma-2 (Bcl-2), Caspase-3 (Caspase-3), apoptosis-promoting substance (Bax)], PD-1/PD-L1 [soluble PD-L1 (sPD-L1), CD4 + T cell surface PD-1 expression (PD-1 CD4 + T cells), CD8 + T cell surface PD-1 expression (PD-1 CD8 + T cell) and CD14 + monocyte surface PD-L1 expression (PD-L1 CD14 + monocyte)], safety and survival rate within 1 year were compared between the two groups. Results:(1) Disease control and safety: the objective response rate and disease control rate of the observation group were 80.39%(41/51) and 92.16%(47/51), respectively, which were higher than those of the control group by 39.22%(20/51) and 70.59%(36/51) (all P<0.05), but there was no significant difference in the incidence of side effects between the groups (all P>0.05). (2) Tumor markers and proliferation and apoptosis indexes: compared with those before treatment, the levels of serum SCCAg, CYFRA21-1, CEA, CA125, survivin and Bcl-2 in the two groups after treatment were significantly lower, and the levels of Caspase-3 and Bax were significantly higher; the above indexes in the observation group were better than those in the control group after treatment (all P<0.05). (3) PD-1/PD-L1: after treatment, sPD-L1, PD-1 CD4 + T cells, PD-1 CD8 + T cells and PD-L1 CD14 + monocytes in the observation group were significantly lower than those before treatment (all P<0.05). After treatment, the sPD-L1, PD-1 CD4 + T cells, PD-1 CD8 + T cells, PD-L1 CD14 + monocytes in the observation group were lower than those in the control group (all P<0.05). (4) Survival: the survival rate of the observation group was higher than that of the control group within 1 year ( P<0.05). Conclusions:The clinical effect of anti-PD-1/PD-L1 immunotherapy combined with concurrent radiotherapy and chemotherapy in the treatment of LACC is significant. It can effectively inhibit the progression of the disease by regulating tumor markers, proliferation and apoptosis indicators and PD-1/PD-L1 expression without increasing the risk of treatment, and has a positive effect on improving the survival rate of patients.
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Objective:To investigate the analgesic effect of ultrasound-guided pericapsular nerve group (PENG) block combined with laryngeal mask general anesthesia and internal fixation of proximal femoral nail antirotation (PFNA) under ERAS concept in elderly patients.Methods:A total of 50 elderly patients with femoral trochanteric fractures treated with PFNA internal fixation who were admitted to Changsha Central Hospital from January 2021 to March 2022 were selected and according to the random number table method, they were divided into groups P and F, with 26 cases in group P (ultrasound-guided PENG block combined with laryngeal mask general anesthesia group) and 24 cases in group F [ultrasound-guided fascia iliaca compartment block (FICB)] combined with laryngeal mask general anesthesia group]. The bispectral index (BIS) of the two groups of patients was maintained within the range of 40-60, and the dosage of cyclopofol and remifentanil was adjusted according to the BIS and hemodynamic changes. Postoperative oxycodone was used for patient controlled intravenous analgesia (PCIA). When the Visual Analogue Scale (VAS) score ≥4, 1 mg intravenous oxycodone was administered as rescue analgesia. The VAS score was observed and recorded before nerve block (T 0), 10 minutes after nerve block (T 1), 20 minutes after nerve block (T 2), when the patients were placed in body position after bed (T 3), after laryngeal mask removal (T 4), 12 h after operation (T 5), 24 h after operation (T 6) and 48 h after operation (T 7). The mean arterial pressure (MAP), heart rate (HR) and blood oxygen saturation (SpO 2) at each time point from T 0 to T 4 were observed and recorded; the intraoperative dose of remifentanil, the rescue dose of oxycodone at postoperative T 6 and T 7, Lovett muscle strength score, anesthesia operation time, anesthesia recovery time and postoperative anesthesia-related complications were recorded. Results:There was no significant difference between the two groups in VAS scores at T 0, T 4, T 5 and T 6, MAP, HR and SpO 2 at T 0, T 1, T 2 and T 4, the dosage of remifentanil during operation, the remedial dosage of oxycodone at T 6 after operation, anesthesia operation time and anesthesia recovery time (all P>0.05). Compared with group F, the VAS scores of group P at T 1, T 2, T 3 and T 7 were lower than those of group F (all P<0.05); At T 3, there was no significant difference in SpO 2 between the two groups ( P>0.05), but the MAP and HR in group P was lower than that in group F (all P<0.05); The remedial dose of oxycodone at T 7 in group P was lower than that in group F ( P<0.05), and the analgesic effect was longer; Lovett muscle strength score at T 6 and T 7 in group P was better than that in group F (all P<0.05). There was no significant difference in the incidence of postoperative complications between the two groups ( P>0.05). Conclusions:Compared with FICB, ultrasound-guided PENG block used in PFNA internal fixation in elderly patients has faster effect, lower dosage of opioid analgesics, longer duration of analgesia, and less impact on postoperative lower limb muscle strength.
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Objective:To study on the effect of ultrasound-guided thoracic paravertebral nerve (TPVB) block on quality of recovery from general anesthesia in tuberculosis patients with fiberboard exfoliation in post anesthesia recovery unit (PACU).Methods:From May 2018 to December 2019, 40 tuberculosis patients in Changsha Central Hospital with pulmonary fibreboard exfoliation and focal abscess lesions cleaning were randomly divided into two groups, with 20 patients in each group. The patients in group A received endobronchial general anesthesia and in group B received ultrasound-guided TPVB combined with endobronchial general anesthesia. Patients in the two groups were maintained under anesthesia by propofol, and the bispectral index (BIS) was maintained within the range of 40-50. The dosage of propofol and sufentanil was adjusted according to changes in BIS and hemodynamics. The mean arterial pressure (MAP), heart rate (HR) in two groups of patients were recorded at before anesthesia induction (T 0), before cutting leather (T 1), cut skin after (T 2), the end of operation (T 3), extubation time (T 4), and T 5 (time of leaving PACU). The visual analogue scale (VAS) of all patients in resting and cough state was recorded at 5, 30 min after extubation and the time of leaving PACU. The dosage of propofol and sufentanil in the operation and the additional dosage of sufentanil in PACU were recorded in both two groups. And the respiratory recovery time, consciousness recovery time, extubation time and sedation agitation scale(SAS) were observed. The adverse reactions such as nausea, vomiting, drowsiness and hypotension were observed in PACU. Results:Compared with group A, MAP and HR of patients at T 2, T 3, T 4, T 5 in group B were more stable during anesthesia, and VAS of patients in group B were lower than that in group A at each time point after extubation ( P<0.05). The dosage of sufentanil and propofol in group B were (35.92±8.12)μg and (749.56±95.30)mg respectively, which were significantly lower than those in group A [(45.74±4.42)μg and (862.83±105.34)mg, P<0.05]; the dosage of sufentanil in postoperative anesthesia recovery room of group B was (5.26±2.10)μg, significantly less than that of group A (10.35±5.86)μg ( P<0.05). The respiratory recovery time, consciousness recovery time and extubation time in group B were (12.92±5.12) min, (20.56±5.10) min and (26.87 ± 6.16) min, which were shorter than those in group A [(15.74±4.72)min, (25.83±5.34)min and (35.35±5.80)min, P<0.05]. The incidence of postoperative nausea, vomiting, lethargy and hypotension in group B were 10%, 10%, 35% and 20%, which were significantly lower than those in group A (30%, 20%, 75% and 45%, P<0.05). Conclusions:Ultrasound-guided paravertebral nerve block may significantly reduce the dosage of opioid analgesics for general anesthesia in tuberculosis patients with fiberboard exfoliation, accelerate the speed of anesthesia recovery, reduce the agitation during recovery, and improve the quality of anesthesia recovery.
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Objective:To investigate the effect and potential mechanism of miR-199a-5p on the radiosensitivity of cervical cancer CaSki cells.Methods:Cervical cancer CaSki cells were cultured in vitro. MiR-199a-5p mimics (miR-199a-5p mimics) were transfected into cervical cancer CaSki cells (miR-199a-5p group) with liposome by Lipofectamine 2000. CaSki cells transfected with mimics control were used as negative control (NC group) and non transfected CaSki cells were used as blank control (control group). After X-ray irradiation, real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-199a-5p in cells of each group. The effects of miR-199a-5p on radiosensitivity and apoptosis of CaSki cells were detected by clone formation assay and flow cytometry apoptosis assay. Bioinformatics software was used to predict the target gene of miR-199a-5p. Double luciferase reporter gene assay and Western blot were used to verify the targeting relationship between miR-199a-5p and thyroid hormone receptor interaction factor 4 (TRIP4). Results:The expression of miR-199a-5p in miR-199a-5p group was significantly higher than that in control group ( P<0.05). After X-ray irradiation, the expression of miR-199a-5p was more obvious ( P<0.05); Overexpression of miR-199a-5p could reduce the clonogenic ability and promote the apoptosis of CaSki cells ( P<0.05); Overexpression of miR-199a-5p could further reduce the clonal formation and promote the apoptosis of irradiated cells ( P<0.05); Double luciferase reporter gene experiment and Western blot confirmed that miR-199a-5p could target and negatively regulate TRIP4. Conclusions:miR-199a-5p can increase the radiosensitivity of cervical cancer CaSki cells by negatively regulating the expression of TRIP4.
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Objective To evaluate the safety,efficacy and comfort of dexmedetomidine sedation combined with ultrasound-guided ilioinguinal and ilioinguinal nerve block in open inguinal hernia surgery for elderly patients with underlying diseases.Methods 40 elderly patients for open inguinal hernia surgery with underlying diseases were selected and randomly divided into group A and group B.Group A recived simple nerve block,while group B recived dextropyrimidine sedation combined with nerve block.The heart rate (HR),mean arterial pressure (MAP),SpO2,Ramsay sedation score and visual analogue score (VAS) at T0 (entering operating room),T1 (anesthesia puncture),T2 (15 min after anesthesia),T3 (surgical incision),T4 (hernia sac free),T5 (operation ending) in both two groups were recorded,and the intraoperative anesthesia effect were evaluated.The satisfaction rate,incidence of bradycardia,bradycardia and respiratory depression were compared between the two groups;and observed the sufentanil using,lidocaine using and the occurrence of adverse reactions.Results There was no significant difference of SpO2 at each time point between the two groups (P ＞ 0.05);HR,MAP and Ramsay sedation scores at T0 between the two groups had no significant difference (P ＞ 0.05);compared with group A,HR,MAP and Ramsay scores at T1-T5 in group B decreased and Ramsay scores increased,while VAS at T1,T3,T4 and T5 in group B were lower (P ＜ 0.05);in group B,local anesthesia with lidocaine at puncture point,intraoperative sufentanil and body movement were significantly reduced,and the overall satisfaction rate of patients was high (P ＜ 0.05).There were no obvious adverse reactions in both groups.Conclusions Dexmedetomidine sedation combined with ilioinguinal/iliohypogastric nerve block is safe and effective in elderly patients with open hernia surgery combined with basic diseases,and it can improve the comfort of patients during anesthesia puncture and operation more than simple nerve block.
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Objective To evaluate the effect of dexmedetomidine on autophagy during ischemiareperfusion (I/R) injury in isolated rat lungs.Methods SPF healthy male Sprague-Dawley rats,weighing 250-320 g,were anesthetized with atropine and pentobarbital sodium,and their lungs were excised to establish the isolated lung perfusion model.Thirty lungs in which isolated lung peffusion models were successfully established were divided into 3 groups (n=10 each) by a random number table method:control group (C group),lung I/R group (I/R group) and dexmedetomidine group (DEX group).The isolated rat lungs were continuously perfused for 150 min in C group.After 15 main of perfusion,the isolated lungs were subjected to 60 min of ischemia and apnea followed by 75 min of ventilation and reperfusion to establish the model of isolated lung I/R injury in I/R group.In DEX group,the isolated lungs were perfused for 15 min with K-H perfusion fluid containing 10 nmol/L dexmedetomidine,and then subjected to 60 min of ischemia and apnea followed by 75 min of ventilation and reperfusion with K-H perfusion fluid containing 10 nmol/L dexmedetomidine.Pulmonary vascular resistance (PVR) and partial pressure of arterial oxygen (PaO2) were recorded at 10 min of perfusion and 15,45 and 75 min of reperfusion.Lung tissues were collected at 75 min of reperfusion for measurement of lung wet weight (W) and dry weight (D) and for examination of morphological changes of lung tissues (with a light microscope) and autophagic vacuoles of lung cells (under an electron microscope).The W/D ratio and lung injury score were calculated.The expression of mammalian target of rapamycin (mTOR),phosphorylated mTOR (p-mTOR) and microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ) in lung tissues was detected by Western blot.Results Compared with C group,the PVR,W/D ratio and lung injury score were significantly increased,the expression of LC3 Ⅱ was up-regulated,and PaO2 was decreased in I/R group and DEX group (P＜0.05).Compared with I/R group,the PVR,W/D ratio and lung injury score were significantly decreased,the expression of LC3 Ⅱ was down-regulated,PaO2 was increased,and the expression of mTOR and p-mTOR was up-regulated in DEX group (P＜0.05).A lot of autophagic vacuoles of lung cells were found in I/R group,and a few autophagic vacuoles of lung cells were observed in DEX group.Conclusion The mechanism by which dexmedetomidine reduces isolated lung I/R injury is related to inhibiting autophagy in rats.
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Objective To investigate the effects of dexmedetomidine on inflammatory response and lipid peroxidation during lung ischemia?reperfusion(I∕R)in rats. Methods Thirty lungs, which were i?solated from SPF adult male Sprageue?Dawley rats, in which the model of isolated lung perfusion was suc?cessfully established, were divided into 3 groups(n=10 each)using a random number table: sham oper?ation group(S group), I∕R group and dexmedetomidine group(D group). The lungs were subjected to 60 min of ischemia and apnea after 15?min ischemia followed by 75 min of reperfusion and ventilation to estab?lish the model of isolated lung I∕R injury. In group D, the lungs were perfused with K?H solution containing 10 nmol∕L dexmedetomidine for 15 min and then subjected to 60 min of ischemia and apnea followed by ven?tilation and reperfusion with K?H sloution containing 10 nmol∕L dexmedetomidine for 75 min. Airway resist?ance, lung compliance, perfusion flow and partial pressure of arterial oxygen(PaO2)were recorded at 10 min of perfusion(T0)and 15, 45 and 75 min after restoration of perfusion(T1?3). Lung tissues were ob?tained at 75 min after restoration of perfusion for determination of wet∕dry weight ratio(W∕D ratio)and for examination of pathological changes and ultrastructure of lungs. The activity of superoxide dismutase (SOD)and content of malondialdehyde(MDA)in lung tissues were measured by improved pyrogallol au?toxidation method and thiobarbituric acid method, respectively. The expression of β?endorphin and interleu?kin?8(IL?8)in lung tissues was detected by Western blot. Results Compared with group S, the airway resistance was significantly increased, and the lung compliance, perfusion flow and PaO2were decreased during the perfusion restoration period, the W∕D ratio and content of MDA were increased, the activity of SOD was decreased, and the expression of β?endorphin and IL?8 was up?regulated in I∕R and D groups (P<0.05). Compared with group I∕R, the airway resistance was significantly decreased, and the lung compliance, perfusion flow and PaO2were increased during the perfusion restoration period, the W∕D ratio and content of MDA were decreased, the activity of SOD was increased, the expression of β?endorphin and IL?8 was down?regulated(P<0.05), and the pathological changes of lungs were significantly attenuated in group D. Conclusion The mechanism by which dexmedetomidine reduces lung I∕R injury may be related to inhibiting lipid peroxidation and inflammatory response of lung tissues in rats.
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Objective To evaluate the effects of dexmedetomidine on the expression of aquaporins 1 (AQP1) and AQP5 during lung ischemia/reperfusion (I/R) in rats in an in vitro experiment.Methods SPF healthy male Sprague-Dawley rats,aged 3-4 months,weighing 250-320 g,were used in this study.Forty-five isolated rat lungs in which the model of isolated lung perfusion was successfully established were divided into 3 groups (n=15 each) using a random number table:sham operation group (S group),I/R group and dexmedetomidine group (D group).The isolated rat lungs were continuously perfused for 150 min in group S.After 15 min of perfusion,the isolated rat lungs were subjected to 60 min of ischemia and apnea followed by 75 min of ventilation and reperfusion to establish the model of isolated lung I/R injury in group I/R.In group D,the isolated rat lungs were perfused for 15 min with K-H perfusion fluid containing 10 nmol/L dexmedetomidine,and then subjected to 60 min of ischemia and apnea followed by 75 min of ventilation and reperfusion with K-H perfusion fluid containing 10 nmol/L dexmedetotnidine.The lung compliance,airway resistance,perfusion flow and partial pressure of arterial oxygen (PaO2) were recorded at 10 min of perfusion and 15,45 and 75 min after restoration of perfusion.Lung tissues were obtained at 75 min after restoration of perfusion for determination of wet/dry weight ratio (W/D ratio) and for examination of the pathological changes and changes in the uhrastructure.The expression of AQP1 and AQP5 protein and mRNA in lung tissues was detected by Western blot and real-time polymerase chain reaction,respectively.Results Compared with S group,the airway resistance was significantly increased and lung compliance,perfusion flow and PaO2 were decreased during reperfusion,and W/D ratio was increased in I/R and D groups (P＜0.05),the expression of AQP1 and AQP5 protein and mRNA in lung tissues was significantly down-regulated in group I/R,and the expression of AQP 1 and AQP5 protein and mRNA in lung tissues was significantly up-regulated in group D (P＜0.05).Compared with I/R group,the airway resistance was significantly decreased and lung compliance,perfusion flow and PaO2 were increased during reperfusion,W/D ratio was decreased,the expression of AQP1 and AQP5 protein and mRNA in lung tissues was up-regulated (P＜0.05),and the pathological changes of lung tissues was significantly attenuated in group D.Conclusion The mechanism by which dexmedetomidine reduces I/R injury may be related to up-regulation of the expression of AQP1 and AQP5 in rats in an in vitro experiment.
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Objective To evaluate the diagnostic value of the level of plasma D-dimer, lipoproteins and carcino-embry-onic antigen(CEA) in gastrointestinal cancer.Methods The plasma D-dimer ,lipoproteins,CEA and clinicopathological data of 139 gastrointestinal cancer patients and 155 normal controls were collected and analyzed .Lipoproteins included high-density lipoprotein(HDL),low-density lipoprotein(LDL) and lipoprotein a[LP(a)].SPSS 13.0 statistical software was used to analyze the sensitivity and specificity of each examination method and to find the appropriate combination .Results The plasma D-dimer,LDL,LP( a) and CEA levels were distinctly higher in patients than those in normal controls ( P<0.001).HDL levels were significantly lower in patients than those in normal controls (P<0.001).The cutoff of D-dimer was 0.495 μg/ml , the sensitivity of D-dimer was 62.6%,and the specificity was 86.5%.The cutoff of HDL was 1.025 mmol/L, the sensitivity was 72.7%,and the specificity was 85.2%.The cutoff of LDL was 3.375 mmol/L, the sensitivity was 54%,and the specificity was 82.6%.The cutoff of LP(a) was 27.3 mg/dl, the sensitivity was 58.3%,and the speci-ficity was 87.1%.The cutoff of CEA was 2.14 ng/ml, the sensitivity was 59.7%,and the specificity was 76.8%.The sensitivity and specificity of HDL +CEA were 77.7%and 88.4%, respectively.The sensitivity and specificity of HDL +D-dimer were 70.5% and 96.1%, respectively.The sensitivity of HDL +LP(a) was 76.3%,and the specificity was 93.5%.The sensitivity of D-dimer +HDL+LP(a) was 84.2%,and the specificity was 92.3%.The sensitivity of D-dimer +HDL+CEA was 87.1%, and the specificity was 85.8%.The sensitivity and specificity of HDL +LP(a) +CEA were 85.6%and 92.3%, respectively.The sensitivity of D-dimer +HDL+CEA +LP(a) was 89.9%while the specificity was 92.3%.Conclusions Plasma D-dimer and lipoproteins can serve as tumor markers in gastrointestinal cancer .Combined detection has higher sensitivity and specificity .