Objective To evaluate the effect of dexmedetomidine on cognitive dysfunction after thoracic surgery in patients undergoing one-lung ventilation.Methods Sixty-two patients,aged 45-64 yr,of ASA physical status Ⅰ or Ⅱ,with body mass index ranged from 17.5 to 25.5 kg/m2,scheduled for elective thoracic surgery,were randomly allocated into 2 groups (n =31 each) using a random number table:dexmedetomidine group (Dex group) and control group (C group).Dexmedetomidine 0.5 μg/kg was infused for 10 min starting from the time point before induction of anesthesia,followed by continuous infusion at a rate of 0.5 μg · kg-1 · h-1 until 30 min before the end of surgery in Dex group.The equal volume of normal saline was administered instead in group C.Before induction and at 24,48 and 72 h after surgery,venous blood samples were collected for determination of levels of S-100 beta protein and neuronspecific enolase in serum by ELISA.Cognitive function was assessed by Mini-Mental State Examination at 72 h after surgery.Results The levels of S-100 beta protein and neuron-specific enolase in serum were significantly increased after surgery than before induction in the two groups.Compared to C group,the levels of S-100 beta protein and neuron-specific enolase in serum were significantly decreased after surgery,and the incidence of postoperative cognitive dysfunction was decreased in Dex group (26％ vs 6％).Conclusion Dexmedetomidine can effectively reduce the nerve damage during one-lung ventilation and significantly inhibit the development of postoperative cognitive dysfunction in patients undergoing thoracic surgery,indicating that dexmedetomidine is suitable for thoracic surgery.

As a weapon of mass destruction ,the biological weapon , composed of biological warfare agents and their re-lease devices,is characterized by strong pathogenicity , large pollution areas, various routes of infection, low cost, user-friendliness and a large number of impact factors .Although the United Nations has banned the use of biological weapons , there are still some countries and regions that continue biological weapon researches .In addition, illegal use of biological warfare agents in the field of terrorism and non-military arena poses a serious threat to public safety .Early detection of bio-logical warfare agent use and determination of its type are crucial to biological weapon defense and epidemic control .There-fore, to enhance researches on rapid detection and early warning of biological warfare agents is of great significance .This paper reviews the main technologies currently applied to the field of biological warfare agent detection and their progress .

Objective To investigate the changes of plasma ghrelin,growth hormone (GH) and growth hormone releasing hormone (GHRH) and gastric ghrelin in patients with chronic obstructive pulmonary disease( COPD ) and to explore their clinical significances.Methods Plasma ghrelin,GH,GHRH,TNFα,IL-6 and C reactive protein (CRP) were measured in 40 COPD patients and 20 controls with chronic bronchitis. Correlated factors of plasma ghrelin,TNFα,IL-6,CRP were analyzed. Body composition was assessed with bioelectrical impedance analysis.The expression of gastric ghrelin in patients with COPD was detected.Results Plasma ghrelin was higher in the underweight patients than in the normal weight patients and in the controls [ ( 1.78 ± 0.46 ) ng/L,( 1.39 ± 0.46 ) ng/L,( 1.36 ± 0.39 ) ng/L,respectively].Plasma GH was lower in the underweight patients than in the normal weight patients and in the controls [(4.12 ±0.83) μg,/L,(5.17 ±0.72) μg/L,(6.49 ± 1.13) μg/L,respectively].Plasma GHRH was lower in the underweight patients than in the normal weight patients and in the controls [ (20.43 ± 4.41 ) ng/L,(23.47 ± 3.97) ng/L,( 27.48 ± 10.06) ng/L,respectively ].Plasma ghrelin was higher in the underweight patients than in the controls ( P ＜ 0.01 ).Plasma ghrelin was higher in the underweight patients than in the normal weight patients with COPD.Plasma ghrelin (log transformed) was negatively correlated with BMI and percentage of body fat in the COPD patients.Plasma GHRH was positively correlated with ghrelin in the underweight patients ( r =0.515,P ＜ 0.05 ),while no correlation was found between plasma G H and ghrelin in the underweight patients (r =0.415,P ＞ 0.05 ).Plasma ghrelin was positively correlated with TNFα and IL-6 in the underweight patients.The gastric expression of ghrelin showed no evident difference between the patients with COPD and the controls.Conclusions The plasma GH in COPD patients may not be correlated with ghrelin.The plasma ghrelin level may be a useful indicator for malnutrition in COPD patients.Plasma ghrelin might be involved in the pathogenesis of CODP by affecting the body energy metabolism.

Objective To investigate the effect of nCPAP as pre-emptive ventilatory support strategy in severe bronchiolitis. Methods A retrospective analysis was made on cases with nCPAP as pre-emptive ventilatory support strategy for severe bronchiolitis in PICU of our hospital from August 2012 to September 2014. Results Seventy-nine children received nCPAP therapy in our PICU. Overall, nCPAP was successful performed in 69 children, 10 patients required intubations. PaO2 and PaO2/FiO2 in patients received intubations were lower than those in patients received only nCPAP before treatment (P < 0.05). There were significant improvements in PaCO2, PaO2, PaO2/FiO2, respiratory rate and heart rate in the patients received only nCPAP at 12 hours and 24 hours post-treatment (P < 0.05). For the 69 patients with hypercapnia received only nCPAP, PaCO2 was significantly reduced at 2 hours, 12 hours and 24 hours post-treatment (P < 0.01). Conclusion Clinically, nCPAP could improve the oxygenation and hypercapnia of patients with severe bronchiolitis. However, these patients, who suffered from severe bronchiolitis with minor PaO2 or PaO2/FiO2, appeared to require intubation as soon as possible.

Objective To test the hypothesis that p53 gene therapy combined with endostatin can enhance tumor response to radiation therapy of RM-1 mouse xenograft prostate cancer and to investigate its mechanism. Methods A mouse prostate cancer model was established. Then mice with xenograft tumor were randomly divided into group A (control), B (radiation), C (radiation and rAdp53), D (radiation and rh-endostatin) and E (radiation and rAdp53 and rh-endostatin). On day 1, rAdp53 was injected intra-tumorously with 1 × 1010 vp per animal to group C and E. From day 1 to 14, rh-endostatin was given 15 mg/kg intraperitoneally daily to group D and E. On day 4 single fraction of 15 Gy was given to tumors in groups B, C, D and E. Normal saline was injected intra-tumorously or intraperitoneaUy accordingly as control. No treatment was done to group A. Tumor volume was measured daily. Samples were collected on Days 5, 10 and 15. Ki67, CD31, p53 and VEGF were detected by means of immunohistochemistry. Results (1) Radiation alone, radiation combined with intra-tumorous injection of Adp53 and/or intraperitoneal injection of rh-endostatin resulted in tumor growth arrest of RM-1 cells in vivo (P = 0.000). Radiation combined with both rAdp53 and rh-endostatin was the most effective treatment (P < 0.05). (2) All the four treatment groups had a decreased expression of mutant type P53 (P = 0.000). The expression of Ki67 in groups B and C were equal (P 0.05) and increasing (P = 0.000), respectively. Group D had a up-down-up curve (P < 0.05), but group E had a up-down one. On day 5 the expresion of VEGF in group E was the lowest (P < 0.05). An increased expression of MVD compared with the control was shown, and MVD in groups C, D and E were always higher than that in the control (P < 0.05). Conclusions The limitation of radiotherapy could be overcome by combination with beth p53 gene therapy and endostatin on the growth of mouse prostate cancer cell. Radiation, rAdp53 and endostatin have their own role but they can be interacted with each other.

Objective To evaluate the role of C-X-C chemokine receptor type 4 ( CXCR4) in the dorsal root ganglia ( DRG) in incisional pain in rats. Methods Thirty-two male Sprague-Dawley rats, aged 7-10 weeks, weighing 250-300 g, in which intrathecal catheters were successfully implanted, were divided into 4 groups (n＝8 each) using a random number table method: sham operation group (group S), CXCR4 antagonist AMD3100 plus sham operation group (group A+S), incisional pain group (group I) and CXCR4 antagonist AMD3100 plus incisional pain group (group A+I). Rats were anesthetized with sevoflu-rane. AMD3100 20 μg (in 10 μl of normal saline) was intrathecally injected, and no incision was made 30 min later in group A+S. A 1-cm longitudinal incision was made through skin, fascia and muscle of the plantar aspect of the left hindpaw in group I. AMD3100 20 μg (in 10 μl of normal saline) was intrathecally injected, and 30 min later the model of incisional pain was established in group A+I. The mechanical paw withdrawal threshold ( MWT) and thermal paw withdrawal latency ( TWL) were measured at 24 h before surgery and 2, 4, 8, 16 and 24 h after surgery. The rats were sacrificed after the last measurement of pain threshold and the DRGs of the lumbar segment (L4-6) were removed for detecting the expression of CXCR4, phosphorylated extracellular regulated protein kinase ( p-ERK) and total ERK ( t-ERK) by Western blot. Results Compared with group S, MWT was significantly decreased and TWL was shortened at T1-5in group I and group A+I, and the expression of CXCR4 and p-ERK in DRGs was significantly up-regulated (P＜0. 05), and no significant change was found in the expression of t-ERK in group I, no significant change was found in the expression of CXCR4, p-ERK and t-ERK in group A+I, and no significant change was found in the parameters mentioned above in group A+S (P＞0. 05). Compared with group I, MWT was significantly increased and TWL was prolonged at T1-5, the expression of CXCR4 and p-ERK in DRGs was down-regulated (P＜0. 05), and no significant change was found in the expression of t-ERK in group A+I (P＞0. 05). Conclusion CXCR4 in DRGs is involved in incisional pain, and the mechanism may be re-lated to activating ERK1∕2 signaling pathway in rats.

Objective:To explore the effect of enriched environment on pain sensitivity, anxiety- and depressive-like behavior in selective nerve injury(SNI) rats model and its potential mechanism.Methods:A total of 36 male clean grade SD rats aged 6-8 weeks were randomly divided into three groups( n=12 in each group): sham operation+ standard environment group (sham group), SNI+ standard environment group (standard environment group), SNI+ enriched environment group (enriched environment group). The rat model of neuropathic pain was established by SNI.The rats in the enriched enviroment group were placed in an enriched enviroment 7 days before operation until 21 days after operation.The paw withdraw threshold(PWT) and paw withdraw latency (PWL) were performed to assess hyperalgesia.The open field test, elevated plus maze test, novelty suppressed feeding test and forced swimming test were used to assess anxiety and depression like behavior.The expressions of cAMP response element binding protein (CREB), p-CREB, brain-derived neurotrophic factor (BDNF), postsynaptic density-95 (PSD-95) and neuroligin 2 (NLGN2) were detected by Western blot.The expression of CREB and BDNF in contralateral ACC were measured by immunofluorescence.GraphPad prism 8.0 and SPSS 23.0 were used for data analysis.One way ANOVA was used for inter group comparison, repeated measurement ANOVA was used to analyze PWT and PWL results, and Tukey test was used for pairwise comparison. Results:(1) In PWT and PWL experiments, the interaction effect between group and time, group main effect and time main effect of PWT were significant ( F=13.4, 39.6, 369.6, all P<0.05), and the interaction effect between group and time, group main effect and time main effect of PWL were significant ( F=3.8, 10.3, 58.8, all P<0.05). Compared with sham group, PWT((8.0±3.5) g, (2.4±1.4) g, (2.3±1.1) g, (2.2±1.6) g, (1.6±0.5) g) and PWL((8.6±1.3) s, (7.3±1.5) s, (7.9±1.0) s, (6.6±1.1) s, (7.7±1.4) s) in standard environment group decreased at each time point (all P<0.05). (2) Compared with sham group, the number of entrying into the central area (1.3±1.7), the time of entrying into the central area((1.6±1.3) s), the proportion of entering open arms ((8.0±7.8) %) and the proportion of time in the open arms ((1.3±1.2) %) all significantly decreased in standard environment group ( t=4.585, 5.423, 4.682, 5.202, all P<0.05). The eating latency ((365.2±94.4) s) and immobility time ((127.6±24.3) s) dramatically increased ( t=6.008, 14.290, both P<0.05). The number and time of entrying into central area of enriched environment group were both higher than those of standard environment group(both P<0.05), while the eating latency and immobility time of enriched environment group were both lower than those of standard environment group(both P<0.05). (3) Compared with sham group(CREB: (1.6±0.2), (0.8±0.5); BDNF: (0.8±0.5), (1.0±0.4)), the expression of CREB ((1.8±0.1), (1.5±0.2)), BDNF ((0.9±0.6), (1.4±0.3)) in spinal cord and ACC of standard environment group increased (spinal: t=3.283, 4.989; ACC: t=5.502, 4.257, all P<0.05). The expression of PSD-95 ((1.6±0.2), (1.0±0.2) and NLGN2 ((1.5±0.5), (1.1±0.2)) also increased in ACC of standard enviroment group ( t=4.257, 2.214, both P<0.05). Compared with standard environment group, the expression of CREB (1.3±0.3), BDNF (0.7±0.4), PSD-95(1.0±0.3) and NLGN2(1.1±0.4) in spinal cord of enriched environment group decreased ( t=5.007, 2.166, 2.358, 2.322, all P<0.05). The expression of PSD-95(1.2±0.3) and NLGN2(1.1±0.2) also decreased in ACC of enriched environment group ( t=2.674, 2.944, both P<0.05). However, the expression of p-CREB (1.7±0.6) and BDNF (2.4±0.2) increased in ACC ( t=4.180, 7.610, P<0.05). Conclusion:Enriched environment can improve neuropathic pain and anxiety- and depressive-like behavior in SNI rats, which may be related to the change of synaptic plasticity in spinal cord and ACC.

Objective:To evaluate risk factors for local recurrence and prognosis in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy combined with lymph node dissection (LND).Methods:The data of 237 patients who were diagnosed with UTUC in Peking University First Hospital and received radical nephroureterectomy combined with LND during January 2010 and March 2022 were retrospectively reviewed. Clinicopathologic characteristics and oncological outcomes were compared according to lymph node metastasis. There were 122 males and 115 females. The tumors of 122 cases were located on the left, while 115 cases were on the right. The tumors of 102 cases were in the renal pelvic, 124 cases in the ureter and 11 cases in both sites. The mean age was (65.52±10.14) years old. The overall survival (OS), cancer-specific survival (CSS), local recurrence-free survival (LRFS) of all patients were valued using Kaplan-Meier method, and the survival curves with statistical significance between two groups were analyzed by log-rank test. Univariate and multivariate Cox proportional hazards regressions were performed to identify the independent risk factors for CSS and LRFS.Results:There were 122 males and 115 females. According to the lymph node metastasis, the patients were divided into lymph node negative group ( n=180, 75.9%) and lymph node positive group ( n=57, 24.1%). Lymph node positive group had a higher percentage in renal tumor [57.9%(33/57) vs. 38.1% (69/180)], stage T 3-4 [84.2%(48/57) vs. 32.8%(59/180)], G 3 [91.2%(52/57) vs. 55.6%(100/180)], glandular differentiation [17.5%(10/57) vs. 4.4%(8/180)], sarcomatoid differentiation [22.8%(13/57) vs. 9.4%(17/180)], necrosis [47.4%(27/57) vs. 16.1%(29/180)], lymphovascular invasion [40.4%(23/57) vs. 12.2%(22/180)] and the number of lymph node dissection [ 4(1, 10) vs. 2(1, 5)]. There were significant differences between the two groups ( P<0.05). Of 237 patients, 42 lost of follow up. The median follow-up time was 46(22, 79) months. Among the 195 patients, 52 patients died, and 42 died due to the tumor. Of all patients, 58(29.7%) had local recurrence, 34 had local recurrence alone, and 24 had concurrent distant metastasis. The 5-year OS and CSS were 67.4% and 71.3%, respectively. The 5-year OS and CSS were 70.5% and 75.1% respectively in the lymph node negative group, 57.5% and 59.4% respectively in the lymph node positive group ( P < 0.05). The 3-year LRFS was 68.0% for all the patients. The 3-year LRFS was 75.6% in the lymph node negative group and 44.5% in the lymph node positive group ( P<0.05). Multivariate analysis showed that tumor stage T 3-4( HR =3.924, 95% CI 2.045-7.529, P<0.001) and G 3( HR=2.871, 95% CI 1.193-6.909, P =0.019) were independent risk factors for LRFS. Multivariate analysis showed that age ≥70 years ( HR = 3.578, 95% CI 1.917-6.678, P<0.001) and pathological stage T 3-4 ( HR =2.366, 95% CI 1.278-4.381, P =0.006) were independent risk factors for CSS. Multivariate analysis showed that age ≥70 years ( HR = 3.874, 95% CI 2.190-6.853, P<0.001) and pathological stage T 3-4 ( HR = 2.757, 95% CI 1.565-4.857, P<0.001) were independent risk factors for OS. Conclusions:Patients with high T stage, high grade, as well as glandular differentiation, sarcomatoid differentiation, necrosis, lymphovascular invasion are more likely to have positive lymph node detection. Age ≥70 years and stage T 3-4 were independent risk factors for CSS and OS. Stage T 3-4 and G 3were independent risk factors for LRFS.

BACKGROUNDThe advent of targeted therapy has proved a milestone in the history of metastatic renal cell carcinoma treatment, and several guidelines now recommend sunitinib as first- or second-line treatment. But little is known about its efficacy in Asian patients. The aim of this article was to evaluate the efficacy of sunitinib monotherapy in patients with metastatic renal cell carcinoma treated at two Chinese centers.

METHODSOne hundred and forty-one patients with metastatic renal cell carcinoma were included in the study. Of them, 119 patients received single-agent sunitinib as first-line therapy and the remaining 22 patients received it as second-line therapy. One hundred and twenty patients received sunitinib in a dosage of 50 mg orally once daily on a 4-2 schedule (4 weeks on treatment, 2 weeks off), while 21 patients received 37.5 mg/day continuously until either disease progression or unacceptable toxicity occurred. The overall response rate, survival outcomes, and safety were evaluated.

RESULTSOver a median follow-up time of 23 months (16 cycles; range 2-45 months), complete responses, partial responses, and stable disease lasting two cycles or longer were achieved in 2.8%, 24.1%, and 60.3% of patients respectively (objective response rate 26.9%; overall benefit 87.2%). The median progression-free survival was 14.2 months (range 3-39 months). During the study, 53 patients died and the median survival time was 13.5 months (range 7-25 months). Dose modification or treatment interruption due to adverse events was required in 36.9% of the patients. The most common adverse events were hand-foot syndrome (71.4%), thrombocytopenia (68.8%), hypertension (47.1%), and fatigue (46.3%).

CONCLUSIONSunitinib had a favorable efficacy/tolerability profile in Chinese patients with metastatic renal cell carcinoma.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Renal Cell ; drug therapy ; Female ; Humans ; Indoles ; therapeutic use ; Kidney Neoplasms ; drug therapy ; Male ; Middle Aged ; Pyrroles ; therapeutic use ; Retrospective Studies ; Young Adult