Objective To evaluate the effects of flurbiprofen axetil and fentanyl in postoperative analgesia on immune function and stress response of the patients undergoing esophagectomy. Methods Sixty patients were randomly divided into three groups with 20 cases in each group, including Group F_1 (pre-operative: flurbiprofen axetil 50mg, postoperative : flurbiprofen axetil 50mg + fentanyl 10μg/kg + droperidol 2.5 mg), F_2 (postoperative: flurbiprofen axetil 100mg + fentanyl 10μg/kg + droperidol 2. 5 mg) , and group C (postoperative: fentanyl 10μg/kg + droperidol 2.5 mg). The VAS score was recorded at 1, 24, 48 hours after surgery. Blood samples were obtained from peripheral vein for determination of NE, ACTH, COS, CD3~ + , CD4~+ , CD8~+ and CD4 VCD8~+ at 30min before surgery, 1 d, 2d after surgery. Results Patients in the three groups did not show any significant difference in the VAS scores ( P > 0.05). NE was significantly lower in group F_1 than group F_2 and group C at 1 d after surgery ( P < 0. 05). There were significantly decreased ACTH in group F_2 and F_1 than group C at 1d after surgery( P <0. 05), and it was significantly decreased in group F, than that in group C at 2d after surgery( P < 0.05). COS was significantly decreased in group F_1 than that group C at 1d after surgery( P <0.05 ). CD3~+ T-lymphocytes were significantly higher in group F_2 and F_1 than that group C at 1h after surgery ( P <0. 05) , and group F, was significantly higher than group C at 2d after surgery( P <0.05). CD4~+ T-lymphocytes were significantly increased in group F_1 than that in group C and F_2 at 1d after surgery( P < 0.05). CD8~+ T-lymphocytes were no significantly change in 3 groups and at each time point ( P >0.05). CD4~+/ CD8~+ were significantly higher in group F_1 than that in group C and F_2 at 1 d after surgery( P <0.05). Conclusion Postoperative analgesia by using flurbiprofen axetil and fentanyl can diminish the using dose of postoperative opoiod drug, it can decrease patients postoperative stress level and improve patients cellular immune function.

Objective To study the changes of hippocampal caspase-3 and PSD-95 expression levels in the mice exposed to ketamine 30 mg/(kg·d)for three months. Methods Forty C57BL/6 mice were randomly divided into two groups,and the chronic ketamine addiction model was established by giving mice a three month course of daily intraperitoneal injections of ketamine. Immunohistochemical study and Western blot-ting were applied to observe the expression of caspase-3 and PSD-95 protein. Results There were more expression of caspase-3 and less of PSD-95 in ketamine group as detected by immuohistochemistry. Western blotting results showed caspase-3 active fragment level significantly increased com-pared to saline group,but PSD-95 protein level was decreased. Conclusion The increased level of caspase-3 protein and reduced expression of PSD-95 are observed after long-term ketamine administration. These findings may provide an evidence for the neurotoxicity in mouse hippocampus of chronic ketamine addition as a recreational drug.

Objective To explore the expression of HR and Her?2 in breast cancer primary tumor and axillary lymph node metastasis. Methods Four hundred and twenty?eight female patients with unilateral breast cancer combined with axillary lymph node metastasis treated in the Affiliated Suqian Hospital of Xuzhou Medical University from January 2011 to January 2016 were selected in this study. Immunohistochemistry was used to detect the expression of ER,PR,Her?2 and Ki67 in primary tumor and axillary lymph node metastasis. Results The positive rates of ER expression were 75. 9% ( 325/428 ) and 70. 3% ( 301/428 ) respectively in primary tumor and axillary lymph node metastasis. The positive rates of PR expression were 61. 4% ( 263/428) and 56. 1% ( 240/428 ) respectively in primary tumor and axillary lymph node metastasis. The rates of Her?2 overexpression were 20. 1% ( 86/428) in primary tumor and the positive rate of Her?2 in axillary lymph node metastasis was 22. 7%( 97/428 ) . The positive rates of Ki67 expression were 45. 6%( 195/428 ) and 39. 7%(170/428) respectively in primary tumor and axillary lymph node metastasis. The expression of ER,PR,Her?2 and Ki67 in primary and axillary lymph node metastasis showed no statistical significance ( P>0. 05 ) . The molecular typing of primary tumor and axillary lymph node metastasis were not consistent in 31 patients ( 31/428,7. 24%) ,including 14 cases of primary tumor Luminal A,9 cases of Her?2 overexpression in axillary lymph node metastasis and 5 cases of triple negative breast cancer. Primary tumor Luminal B was detected in 10 cases, while 6 cases of Her?2 overexpression in axillary lymph node metastasis and 4 cases of triple negative breast cancer. Primary tumor Her?2 was overexpressed in 4 cases,while 1 case of Luminal A,3 cases of Luminal B in axillary lymph node metastasis. There were 3 cases of primary tumor triple negative breast cancer,while 2 cases of Luminal B in axillary lymph node metastasis and 1 case of Her?2 overexpression. Conclusion The expressions of ER, PR, Her?2 and Ki67 in primary tumor and axillary lymph node metastasis of some breast cancer were different. Immunohistochemistry for primary tumor and axillary lymph node metastasis of stage II?III breast cancer patients should be routinely carried out. Based on molecular typing of primary tumor and axillary lymph node metastasis,individualized treatment plan can be developed,so that patients will benefit from it.

Objective To evaluate the effect of curcumin on the mammalian target of rapamyein (mTOR) signaling pathway during ischemia-reperfusion (I/R) injury in isolated rat lungs.Methods Sixty-four clean-grade healthy male Sprague-Dawley rats,aged 3-4 months,weighing 250-320 g,were divided into 4 groups (n=16 each) using a random number table method:sham operation group (S group),I/R group,low-dose curcumin group (LC group) and high-dose curcumin group (HC group).The rats only received in vitro perfusion without ischemia in S group.Isolated rat lungs were subjected to 60 min of ischemia followed by 75-min reperfusion to establish the lung I/R injury model in I/R group.Curcumin 5 and 10 μmol/L were added to perfusion fluid from the beginning of reperfusion in LC and HC groups,respectively.Airway resistance (Res),lung compliance,perfusion flow (Flow) and pulmonary venous partial pressure of oxygen (PaO2) were recorded at 10 min of first perfusion (T0) and 15,45 and 75 min of reperfusion (T1-3).Wet/dry lung weight ratio (W/D ratio) was measured at the end of reperfusion.The morphological structure and ultrastructure of lung tissues were observed by using a light microscope and a transmission electron microscope,respectively.The expression of mTOR,Tau protein,nuclear factor kappa B (NF-κB) and tumor necrosis factor-alpha (TNF-α) mRNA in lung tissues was detected by real-time polymerase chain reaction.The expression of mTOR,phosphorylated Tau protein (pS396 Tau protein),NF-κB and TNF-α protein in lung tissues was determined by Western blot.Results Compared with S group,Res at T1-3 and W/D ratio at T3 were significantly increased,lung compliance,Flow and PaO2 were decreased at T1-3,and the expression of mTOR,NF-κB and TNF-α protein and mRNA,Tau protein mRNA and pS396 Tau protein was up-regulated at T3 in I/R,LC and HC groups (P＜0.05).Compared with I/R group,Res at T1-3 and W/D ratio at T3 were significantly decreased,lung compliance,Flow and PaO2 were increased at T1-3,and the expression of mTOR,NF-κB and TNF-α protein and mRNA,Tau protein mRNA and pS396 Tau protein was down-regulated at T3 in LC and HC groups (P＜0.05).Compared with LC group,Res at T1-3 and W/D ratio at T3 were significantly decreased,lung compliance,Flow and PaO2 were increased at T1-3,and the expression of mTOR,NF-κB and TNF-α protein and mRNA,Tau protein mRNA and pS396 Tau protein was down-regulated at T3 in HC group (P＜0.05).The microscopic examination showed that the injury to lung tissues was significantly attenuated in LC and HC groups as compared with I/R group.Conclusion The mechanism by which curcumin reduces I/R injury in isolated rat lungs is related to inhibiting mTOR signaling pathway.

In order to explore the treatment of Her-2 positive breast cancer patients who failed in multi-line treatments, we retrospectively analyzed the clinical data of a patient with refractory Her-2 positive breast cancer.The patient was initially diagnosed as Her-2 positive advanced breast cancer.After six line treatment in the outer hospital, the patient′s condition was basically in a progressive state.The breast tumor was broken and purulent, the lung metastasis increased, and the patient′s quality of life was poor.The patient was admitted to Department of Breast Surgery of Affiliated Suqian Hospital of Xuzhou Medical University, after MDT discussion, we gave pyrrolotinib combined with capecitabine treatment, the chest wound healed gradually, the lung metastasis gradually reduced, and the quality of life was better.A retrospective analysis of this case showed that pyrrolidine combined with capecitabine may bring hope to Her-2 positive breast cancer patients who failed to receive multi-line therapies, especially those who failed to target therapy.

Objective:To evaluate the optimized efficacy of thoracic paravertebral nerve block and subcostal transversus abdominis plane block combined with general anesthesia for elderly patients undergoing thoracic combined with laparoscopic radical resection of esophageal cancer.Methods:Eighty American Society of Anesthesiologists physical status Ⅰ orⅡ patients of both sexes, aged 66-78 yr, weighing 46-80 kg, undergoing elective thoracoscopic combined with laparoscopic radical resection of esophageal cancer, were divided into 2 groups ( n=40 each) using a random number table method: general anesthesia group (group G) and thoracic paravertebral nerve block and subcostal transversus abdominis plane block combined with general anesthesia group (TSG group). Both groups received target-controlled infusion of propofol and remifentanil and intravenous injection of cisatracurium besilate for anesthesia induction and maintenance, with BIS value maintained at 45-60 during operation.Thoracic paravertebral nerve block on the affected side was performed under ultrasound guidance after the end of anesthesia induction, and 0.5% ropivacaine 15 ml was injected in TSG group.The patients were turned to the supine position after the thoracic operation was completed, and the bilateral subcostal approach to the transversus abdominis plane block was performed under ultrasound guidance, and 0.3% ropivacaine 20 ml was injected into each side.Sufentanil was used for patient-controlled intravenous anesthesia (PCIA) after operation.The background infusion rate was 0.05 μg·kg -1·h -1, PCA was 0.04 μg/kg, and the lockout interval was 10 min in group G. The background infusion rate was 0.03 μg·kg -1·h -1, PCA was 0.025 μg/kg, the lockout interval was 10 min in group TSG.Both groups received analgesia until 48 h after operation, and VAS score was maintained ≤3.When VAS score ≥ 4, tramadol 100 mg was intravenously injected for rescue analgesia.At 1 day before operation (T 0), immediately before anesthesia induction (T 1), at 1 h after emergence from anesthesia (T 2), and 4, 8, 12, 24 and 48 h after operation (T 3-7), venous blood samples were collected for determination of serum norepinephrine, epinephrine and cortisol concentrations (by enzyme-linked immunosorbent assay). The intraoperative consumption of remifentanil and occurrence of cardiovascular events were recorded.The pressing times of PCA, consumption of sufentanil and requirement for rescue analgesia within 48 h after operation were recorded.The occurrence of nerve block-related complications (hematoma at the puncture site, infection, local anesthetic poisoning, etc.) and adverse reactions such as nausea and vomiting, respiratory depression and pruritus were recorded within 48 h after the operation. Results:Compared with group G, the concentrations of serum epinephrine, norepinephrine and cortisol were significantly decreased, the consumption of intraoperative remifentanil and postoperative sufentanil and pressing times of PCA were reduced, the rate of rescue analgesia was decreased, scores of satisfaction with analgesia were increased, and the incidence of intraoperative cardiovascular events and postoperative adverse reactions such as nausea and vomiting, pruritus and respiratory depression were decreased in group TSG ( P<0.05). Conclusion:Thoracic paravertebral nerve block and subcostal transversus abdominis plane block combined with general anesthesia can reduce the perioperative consumption of opioids and inhibit perioperative stress responses and postoperative hyperalgesia with fewer adverse reactions when used for the elderly patients undergoing thoracic combined with laparoscopic radical resection of esophageal cancer.

Objective: To analyze the association of cytogenetic abnormalities with the prognosis of chronic myeloid leukemia (CML) patients in tyrosine kinase inhibitors (TKI) era. Methods: Karyotype analysis of chromosome G-banding was carried out in 387 newly diagnosed CML patients by short-term culture of bone marrow cells. The correlation of cytogenetic abnormalities and CML progression was explored in combination with ABL tyrosine point mutations. Result: Of 387 patients with positive BCR-ABL fusion gene assayed by fluorescence in situ hybridization (FISH) technique, 94.1% (364/387) patients were Ph positive and 5.9% (23/387) Ph negative; 320 patients (87.9%) had a translocation t (9;22) (q34;q11) and 5 (1.4%) a variant translocation t (v;22) . Additional cytogenetic aberrations (ACA) at diagnosis were found in 10.7% (39/387) Ph⁺ patients, major route ACA in 22 (56.4%) cases and minor route ACA in 15 (38.5%) cases and 2 patients (5.1%) lacked the Y chromosome (−Y) ; 23.4% (71/303) patients occurred ACA during TKI treatment and the most frequent abnormalities were abnormal chromosome numbersd, which were likely associated with high proportion of disease progression (χ²=168.21, P<0.001) and ABL tyrosine point mutations (χ²=29.04, P<0.001) . Newly diagnosed CML-CP patients with t (9;22) (q34;q11) had a longer event-free survival (EFS) and disease-free survival (DFS) rates than that of patients with ACA (P=0.037; P=0.003) , while the overall survival (OS) had no significant differences (P=0.209) . As for CML-CP patients that occurred ACA during TKI therapy would have a marked low OS, EFS and DFS (all P<0.001) compared with no ACA occurred patients. Survival of advanced patients that occurred ACA were dramatically reduced. Conclusion ACA often emerged during the disease progress in CML patients, regular and timely detection of chromosomes karyotype and ABL tyrosine point mutations during TKI treatment was important for therapeutic evaluation, progress and prognosis of CML.

Objective: To investigate the clinical implications of p16 gene deletion in adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph⁺ ALL) . Methods: Retrospective analysis of clinical, immunophenotypic, cytogenetics, molecular characteristics and prognosis of 80 newly diagnosed Ph⁺ ALL patients with p16 deletion. Results: Of 80 adult Ph⁺ ALL, the prevalence of p16 gene deletion was 31.3%. p16 gene deletion carriers frequently accompanied with high WBC counts (WBC≥30×10⁹/L) and CD20 expression. The incidence of complex chromosome abnormality in p16 gene deletion group was higher than that in non-deletion group, with alternations in chromosome 7, 8, 19 and der (22) more frequently observed. There was no difference occurred between patients with or without p16 gene deletion in complete remission (CR) rate following induction chemotherapy combined with tyrosine kinase inhibitors (TKIs) . However, after three cycles of chemotherapy, the MMR and CMR rate in the p16 gene deletion group was lower than patients with wild-type p16 gene (P=0.034, P=0.036) . The p16 gene deletion patients showed no significant differences in MMR, CMR and relapse rate between Imatinib or Dasatinib plus chemotherapy (P>0.05) . Deletion of p16 gene was significantly associated with poor outcomes including worse overall survival (OS) (37.1% vs 54.1%, P=0.037) , lower disease free-survival (DFS) (12.4% vs 45.9%, P=0.026) , and increased cumulative incidence of relapse (P=0.033) . Among the 25 patients with p16 deletion, 14 underwent allo-HSCT and the median survival was 21 months, better than that of patients received chemotherapy alone (12 months) (P=0.030) . Conclusion This study indicated that deletion of p16 was associated with poor prognosis in adult Ph⁺ ALL, and the utility of second-generation TKI (Dasatinib) does not necessarily have an edge on efficacy over Imatinib, but allo-HSCT has the potential of elongating life expectancy. It is an important significance to define the status of p16 in Ph⁺ ALL for predicting prognosis and guiding therapy decision-making.

Objective:To evaluate the efficacy of esketamine for patient-controlled intravenous analgesia (PCIA) in elderly patients undergoing modified radical mastectomy for breast cancer.Methods:Ninety elderly female patients, aged 65-78 yr, weighing 46-75 kg, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, undergoing elective modified radical surgery for breast cancer under general anesthesia, were divided into 2 groups ( n=45 each) using a random number table method: esketamine PCIA group (group E) and sufentanil PCIA group (group S). Anesthesia was induced with target-controlled infusion of propofol, intravenous atracurium besylate and sufentanil and maintained with target-controlled infusion of propofol and remifentanil and intermittent intravenous boluses of cis-benzenesulfonic acid atracurium.The patients were connected to an analgesic pump for PCIA at 10 min before completion of operation.The PCIA solution in group E contained esketamine 2 mg/kg, ketorolac tromethamine 90 mg and tropisetron 5 mg in 100 ml of normal saline.The PCIA solution in group S contained sufentanil 1 μg/kg, ketorolac tromethamine 90 mg and tropisetron 5 mg in 100 ml of normal saline.The PCA pump was set up with a 1.5 ml bolus dose, a 15 min lockout interval and background infusion at a rate of 1.5 ml/h, and the analgesia was performed until 48 h after operation.When numeric rating scale score ≥ 4 points and the efficacy of patient-controlled analgesia was not good, tramadol 100 mg was intravenously injected for rescue analgesia.Steward recovery scores were recorded at 4, 8, 24 and 48 h after operation.The requirement for rescue analgesia, effective pressing times of analgesic pump and time to first flatus were recorded within 48 h after operation.The nausea and vomiting, respiratory depression, dizziness and pruritus within 48 h after operation and delirium within 7 days after operation were recorded.The 40-item Quality of-Recovery scale was used to evaluate the early postoperative recovery of patients at 24 and 48 h after operation. Results:Compared with group S, the 40-item Quality of Recovery scale score was significantly increased at each time point, postoperative time to first flatus was shortened, the incidence of postoperative nausea and vomiting and pruritus was decreased ( P<0.05), and no significant change was found in the Steward recovery score at each time point after operation, effective pressing times of PCA and requirement for rescue analgesia in group E ( P>0.05). Conclusions:Esketamine provides better efficacy than sufentanil when used for PCIA in elderly patients undergoing modified radical mastectomy for breast cancer.

Objective To explore the effects of dexmedetomidine combined with desflurane anesthesia on cerebral oxygen metabolism,sedation depth and cerebral function in liver cancer patients undergoing partial hepatic lobectomy.Methods A total of 30 liver cancer patients undergoing partial hepatic lobectomy at the Affiliated Cancer Hospital of Zhengzhou University from March to September 2022 were selected as the research subjects,they were divided into control group(n=15)and observation group(n=15)according to different anesthesia methods.Patients in both groups underwent partial open hepatectomy,and they were given the same anesthesia induction method.The patients in the control group received desflurane for anesthesia mainte-nance,while patients in the observation group received dexmedetomidine combined with desflurane for anesthesia maintenance.The anesthesia recovery indexes including the postoperative recovery time,recovery time of spontaneous breathing,eye-opening time of patients between the two groups were compared.The arterial oxygen saturation(SaO2),cervical vein oxygen saturation(SjvO2),arterial partial pressure of oxygen(PaO2)and partial pressure of venous oxygen of patients were detected by blood gas analyzer before anesthesia induction(T0),at the completion of anesthesia induction(T,),at 10 minutes after hepatic portal occlusion(T2),after hepatic lobectomy(T3)and after surgery(T4),and arterio-venous oxygen content difference(AVDO2)and cerebral oxygen extraction rate(CEO2)were calculated.The sedation depth of patients was evaluated by bispectral index(BIS)and patient state index(PSI)at T0,T1,T2,T3 and T4.The cerebral function of patients was evaluated by the Glasgow-Pittsburgh cerebral performance category scale at 3 months after surgery.The incidence of postoperative adverse reactions of patients between the two groups was compared.Results The postoperative recovery time,recovery time of sponta-neous breathing and eye-opening time of patients in the observation group were significantly shorter than those in the control group(P＜0.05).There was no significant difference in SaO2 of patients between the two groups at different time points(P＞0.05).At T2 and T3,SjvO2,AVDO2 and CEO2 of patients in the observation group were significantly lower than those in the control group(P＜0.05),but there was no significant difference in SjvO2,AVDO2 and CEO2 of patients between the two groups at the other time points(P＞0.05).At T2,T3 and T4,BIS and PSI of patients in the observation group were significantly lower than those in the control group(P＜0.05),but there was no significant difference in BIS and PSI of patients between the two groups at T0 and T1(P＞0.05).In the control group,there were 11 patients with postoperative brain function in grade 1,3 patients in grade Ⅱ and 1 patient in grade Ⅲ;in the observation group,there were 12 patients in grade Ⅰ and 3 patients in gradeⅡ.There was no significant difference in postoperative grading of brain function between the two groups(x2=1.044,P＞0.05).There was no significant difference in the total incidence of postoperative adverse reactions between the control group and observation group[20.00％(3/15)vs 26.67％(4/15),x2=0.186,P＞0.05].Conclusion Dexmedetomidine combined with desflurane anesthesia can shorten anesthesia recovery time,improve anesthesia depth and reduce cerebral oxygen metabolism in patients undergoing liver cancer surgery,which has no effect on cerebral function,showing good safety.