BACKGROUND:Fentanyl transdermal system has analgesic effect similar to oral sustained-release morphine and has been widely used in advanced cancer pain management in several years. However, recent literatures about some serious adverse events associated with fentanyl transdermal system have been published, and the long-term safety of fentanyl transdermal system treatment is stil chalenged. OBJECTIVE:To observe the long-term clinical efficacy and safety of fentanyl transdermal system for pain management in patients with advanced cancer. METHODS:A total of 309 patients with advanced cancer pain were enroled, including 166 females and 143 males. The age ranged from 26-72 years old. Patients received oral sustained-release morphine for 2 weeks, and then were subject to fentanyl transdermal system for pain management at the 3rd week until the 12th week. A prospective study with self-contrast method was conducted to compare the analgesic effects of these two drugs, as wel as patient's acceptability, adverse events and toxicity in the administration course. RESULTS AND CONCLUSION: Stable pain relief was harvested throughout the oral administration of both sustained-release morphine and fentanyl transdermal system therapy. During the use of oral sustained-release morphine, adverse reactions appearing in sequence were constipation, nausea, fatigue and anorexia. After converting to fentanyl transdermal system, the symptoms of constipation (χ2=5.22,P=0.02) and nausea (χ2=4.38, P=0.04) significantly reduced, and vomiting was abated but showed no significant difference (χ2=2.7,P=0.10). 2.3% of patients had skin reactions to the patches, and regressed after replacing the patch area. Skin reactions were aleviated at 2-10 weeks after oral administration of fentanyl transdermal system. Some uncommon adverse events including headache, diarrhea, dyspnoea, excessive sweating or other symptoms often occurred at the time of the initial dosage increase. Preference or strong preference for fentanyl transdermal system in comparison to previous oral sustained-release morphine was reported by 91% of patients. These results demonstrate that fentanyl transdermal patches can provide stable pain relief for advanced cancer patients with good acceptability, and mitigate the incidence of adverse events due to oral drugs.

Objective To evaluate the efficacy and safety of management of kidney calculi in non-uronephrosis by percutaneous nephrolithotripsy (PCNL) under ultrasound guidance. Methods From July 2005 to June 2008, 97 cases of kidney calculi in non-uronephrosis were performed by percutaneous nephrolithotripsy. A tube was first inserted into the pelvis through cystoscope, and saline was instilled to dilate collecting system. Antegrade percutaneous access was obtained under ultrasound guidance. A combination of pneumatic and ultrasonic lithotrite was used to disintegrate and remove stone under direct vision. Clinical data including operation time, complications and stone free rate were analyzed retrospectively. Results The perutaneous renal access was successfully established under ultrasound guidance in all patients, immediate phase Ⅰ lithotripsy was performed in 95 cases and delayed phase Ⅱ lithotripsy in 2 cases. Operation time was 70-180 min, average time was (96±23 ) min. The average blood loss was 60 ml (20-500 ml), 4 cases had transfusion during the PCNL and average 400 ml. Minor pyrexia ( < 39℃) was seen in 24 cases,whereas serious pyrexia was noted in 3 cases. Conservatively administered with appropriate antibiotics, the fever disapeared in 27 cases within 5 days postoperatively. Severe complications did not occur during nephrolithotripsy. Stones were cleared completely in 78 out of 97 cases (80.4%)during immediate phase Ⅰ lithotripsy, residual stone fragment was found in 19 cases. Conclusion The management of kidney calculi in non-uronephrosis by PCNL appears to be efficacious and safe under ultrasound guidance.

Objective To evalute the role of phosphatidylinositol 3?kinase(PI3K)∕serine?threo?nine kinase(Akt)∕endothelial nitric oxide synthase(eNOS)signaling pathway in sevoflurane postcondi?tioning?induced attenuation of brain injury in a rat model of hemorrhagic shock and resuscitation(HSR). Methods Seventy?two pathogen?free healthy adult male Sprague?Dawleg rats, weighing 300-350 g, were divided into 4 groups(n=18 each)using a random number table: sham operation group(group S), group HSR, sevoflurane postconditioning group(group SP)and sevoflurane postconditioning plus PI3K∕Akt signaling pathway specific inhibitor wortmannin group(group SP+WT). Hemorrhagic shock was in?duced by withdrawing blood(40% of the total blood volume)from the right common carotid artery over an interval of 30 min, and 1 h later the animals were resuscitated with infusion of the shed blood via the left jugular vein over 30 min. In group SP+WT, wortmannin 0.6 mg∕kg was administrated via the jugular vein at 30 min before establishment of the model. In SP and SP+WT groups, 2.4% sevoflurane was inhaled for 30 min starting from the onset of infusion of the shed blood. At 10 min before withdrawing blood(T0), im?mediately after the end of withdrawing blood(T1), at 30 min and 1 h after the end of withdrawing blood (T2,3)and immediately after infusion of the shed blood(T4), blood samples from the common carotid ar?tery were collected for blood gas analysis, the blood lactate concentration was recorded, and mean arterial pressure was simultaneously recorded. At 24 h after infusion of the shed blood, 6 rats were randomly select?ed from each group and sacrificed, and their brains were immediately removed for determination of cerebral infarct volume(by TTC staining), expression of hippocampal caspase?3(by immuno?histochemistry), and expression of Akt, phosphorylated Akt(p?Akt)and eNOS(by Western blot). The ratio of p?Akt∕Akt was calculated. Results Compared with group S, the mean arterial pressure was significantly decreased and the blood lactate concentration was increased at T1?3, the cerebral infarct volume was increased, and the expression of caspase?3 was up?regulated in the other three groups, and the ratio of p?Akt∕Akt was sig?nificantly increased, and eNOS expression was up?regulated in group SP(P<0.05). Compared with group HSR, the cerebral infarct volume was significantly decreased, the expression of caspase?3 was down?regula?ted, the ratio of p?Akt∕Akt was increased, and eNOS expression was up?regulated in group SP(P<0.05). Compared with group SP, the cerebral infarct volume was significantly increased, the expression of caspase?3 was up?regulated, the ratio of p?Akt∕Akt was decreased, and eNOS expression was down?regula?ted in group SP+WT(P<0.05). Conclusion PI3K∕Akt∕eNOS signaling pathway activation mediates sevoflurane postconditioning?induced attenuation of brain injury in a rat model of HSR.

Objective To evaluate the role of mitochondrial permeability transition pore (mPTP)in reduction of brain injury by sevoflurane postconditioning in a rat model of hemorrhagic shock and resuscitation (HSR).Methods Ninety pathogen-free healthy adult male Sprague-Dawley rats,weighing 300-350 g,were divided into 5 groups (n =18 each) using a random number table:sham operation group (group S),group HSR,sevoflurane postconditioning group (group SP),sevoflurane postconditioning plus atractyloside (ATR,a specific mPTP opener) group (group SP + ATR) and ATR group.Hemorrhagic shock was produced by withdrawing 40％ of the total blood volume from the right carotid artery over an interval of 30 min,and 1 h later the animals were resuscitated by infusion of the shed blood via the left jugular vein over 30 min.SP and SP+ATR groups were exposed to 2.4％ sevoflurane for 30 min starting from the onset of reinfusion.In ATR and SP+ATR groups,ATR 5 mg/kg was intravenously injected at 10 min before reinfusion.Six rats in each group were randomly sacrificed at 24 h after the end of autologous blood reinfusion,and the hippocampus was harvested for determination of the expression of Bcl-2 and Bax in hippocampal tissues (by Western blot) and degree of mPTP opening.At 72 h after the end of autologous blood reinfusion,the rest 6 rats in each group were selected and underwent Morris water maze test,and the cognitive function was evaluated.Results Compared with group S,the escape latency was significantly prolonged,the number of crossing the original platform and locomotor distance in the target quadrant were decreased,the expression of Bcl-2 was down-regulated,the expression of Bax was up-regulated,and the degree of mPTP opening was increased in group HSR (P＜0.05).Compared with group HSR,the escape latency was significantly shortened,the number of crossing the original platform and locomotor distance in the target quadrant were increased,the expression of Bcl-2 was up-regulated,the expression of Bax was down-regulated,and the degree of mPTP opening was decreased in group SP (P＜0.05),and no significant change was found in each parameter in ATR and SP+ATR groups (P＞0.05).Compared with group SP,the escape latency was significantly prolonged,the number of crossing the original platform and locomotor distance in the target quadrant were decreased,the expression of Bcl-2 was down-regulated,the expression of Bax was up-regulated,and the degree of mPTP opening was increased in group SP+ATR (P＜0.05).Conclusion The mechanism by which sevoflurane postconditioning ameliorates brain injury may be related to inhibiting mPTP opening in a rat model of HSR.

Objective:To compare the clinical efficacy and safety of intra-articular injection of platelet rich plasma and hyaluronic acid in the treatment of knee osteoarthritis.Methods:The relevant literatures including the randomized control study of intra-articular injection of platelet rich plasma and hyaluronic acid in the treatment of knee osteoarthritis published from January 2010 to December 2021 were searched. The bias risk of the included literatures was evaluated by Revman 5.3 software, and the data were processed and analyzed by Stata 16.0 software. The weighted mean difference ( WMD) was calculated for the difference ofefficacy indexes, and the difference was compared by t-test. The odds ratio ( OR) was calculated for the difference of safety index, and the difference was compared by t-test. Results:① A total of 10 literatures were included, all of which were in English. ② A total of 921 patients were included in the study, of which 479 patients were treated with intra-articular injection of platelet rich plasma and 442 patients were treated with intra-articular injection of hyaluronic acid. ③ Comparing the VAS scores of platelet rich plasma injection and hyaluronic acid injection, the visual analogue scale (VAS) scores of platelet rich plasma injection patients were significantly lower than those of hyaluronic acid injection patients after 6 and 12 months of injection treatment, and the difference was statistically significant [ WMD(95% CI)=-0.66(-1.25, -0.77), P=0.029; WMD(95% CI)= -0.90(-1.51, -0.29), P=0.004]. ④ The specific performance was that the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score of patients injected with platelet rich plasma after 6 and 12 months of injection treatment was significantly lower than that of patients injected with hyaluronic acid [ WMD(95% CI)=-0.76(-1.06, 0.45), P<0.001; WMD(95% CI)=-1.35(-2.05, -0.65), P<0.01]; After 3, 6 and 12 months of injection treatment, the WOMAC stiffness score of patients injected with platelet rich plasma was significantly lower than that of patients injected with hyaluronic acid [( WMD(95% CI)=-0.37(-0.66, -0.08), P=0.011; WMD(95% CI)=-0.30(-0.57, -0.04), P=0.023; WMD(95% CI)=-0.62(-0.92, -0.33), P<0.001]; After 3, 6 and 12 months of injection treatment, the WOMAC function score of patients injected with platelet rich plasma was significantly lower than that of patients injected with hyaluronic acid [ WMD(95% CI)=-1.90 (-2.53, -1.27), P<0.001; WMD(95% CI)=-5.77(-9.20, -2.34), P=0.001; WMD(95% CI)=-5.72(-8.62, -2.82), P<0.001]. ⑤There was no significant difference in the incidence of adverse events between the two intra-articular injection methods [ OR(95% CI)=1.28(0.68, 2.42), P=0.440]. Conclusion:Compared with intra-articular injection of hyaluronic acid, the short-term clinical efficacy of injection of platelet rich plasma is equivalent to that of injection of hyaluronic acid, but the long-term clinical efficacy is better, and the safety of the two methods is similiar.