OBJECTIVE:To develop a method for the concentration determination of olanzapine,risperidone and paliperidone in human plasma.METHODS:After liquid-liquid extraction,using buspirone hydrochloride as internal standard,the concentration of plasma sample was determined by UPLC-MS/MS.The determination was performed on ACQUITY UPLCTM BEH C18 column with mobile phase consisted of methanol-0.01 mol/L ammonium formate solution (gradient elution) at flow rate of 0.2 mL/min.The column temperature was 45 ℃,and sample size was 5 μL.The electrospray ionization source was adopted for positive ion scanning under MRM mode.Ion-pairs for quantitative analysis were as follows:m/z 313.29→256.25 (olanzapine),m/z 411.42→191.19 (ris peridone),m/z 427.45→207.18 (paliperidone) and m/z 386.43→122.37 (internal standard).RESULTS:The linear ranges of olanzapine,risperidone and paliperidone were 0.426-108.954,0.213-54.476,0.213-54.476 ng/mL,respectively.RSDs of inter-day and intra-day were all lower than 20％.The recoveries of them ranged 83.3％-112.9％,90.0％-109.8％ and 95.2％-114.9％,respective ly.Extraction recoveries ranged 65.5％-95.0％,73.9％-98.5％ and 73.6％-99.4％,respectively.Both plasma matrix effect and dilute effect didn't influence the determination of plasma concentration.The plasma concentrations of olanzapine,risperidone and paliperidone in 100 schizophrenia patients were (103.3 ± 73.6),(13.1 ± 13.1) and (23.2 ± 20.0) ng/mL,respectively.CONCLU SIONS:The method is simple,rapid,sensitive and specific.It can be used for the determination of plasma concentration and pharmacodynamic study of olanzapine,risperidone and paliperidone.

Purpose To observe the changes of left atrial (LA) structure and function in patients with paroxysmal atrial fibrillation after radiofrequency catheter ablation by echocardiography in order to provide basis for clinical evaluation of surgery.Materials and Methods Forty-four patients with paroxysmal atrial fibrillation and treated with radiofrequency catheter ablation in PLA General Hospital from January 2015 to June 2016 were enrolled.According to whether or not to restore sinus rhythm after operation,the patients were divided into sinus rhythm group and atrial fibrillation recurrence group.The paramrters of LA including diameter,maximum and minimum volume,systolic volume,ejection fraction,active ejection fraction,conduit function index and dilatation index were measure by echocardiography before and at least 6 months after radiofrequency catheter ablation.The data were compared between and within groups.Results All patients were followed up for (6.0±0.5) months after ablation operation.29 of 44 patients (66％) maintained sinus rhythm;the anteroposterior,vertical,and left to right diameters of LA in patients with sinus rhythm after operation were significantly lower than those before operation,but the ejection fraction of LA increased (all P＜0.05).However,in patients with atrial fibrillation recurrence after operation,the volume of LA increased (P＜0.05);the diameters of LA did not show significant differences;the ejection and active ejection fraction of LA had significantly decreased (P＜0.05).Compared with patients with sinus rhythm after operation,patients with atrial fibrillation recurrence after operation were older and had higher proportion of hypertension (P＜0.05).Conclusion After ablation,the diameter of LA decreases and the ejection fraction increases in patients with sinus rhythm;the volume of LA increases and the function reduces in patients with atrial fibrillation recurrence.

OBJECTIVETo evaluate the therapeutic effect of MHSP65-TCL on melanoma and its effect on the activity of the immunocytes.

METHODSMHSP65-TCL was prepared by mixing MHSP65 with TCL derived from B16 melanoma cell lysate by repeated freezing and thawing. The MHSP65-TCL vaccine was administered in mice bearing B16 melanoma, and the changes in melanoma growth was observed. To investigate the influence of TCL in MHSP65-TCL on the activity of the immunocytes, we co-cultured TCL and mouse spleen cells in vitro, and analyzed CD69 expression on the cells, cell apoptosis, and levels of IL-10 and IFN-γ in the cell culture supernatant.

RESULTSThe MHSP65-TCL vaccine showed an anti-melanoma effect in the tumor-bearing mice. In the in vitro experiment, TCL in MHSP65-TCL strongly stimulated the activation of mouse spleen cells while causing apoptosis in some of the immunocytes and promoting cellular IL-10 secretion, but not IFN-γ.

CONCLUSIONSMHSP65-TCL derived from B16 melanoma cells has an anti-melanoma effect mediated by the activation of immunocytes. TCL in MHSP65-TCL also has immunosuppressive effect on immunocytes possibly due to the presence of suppressive components in TCL, and identifying and eliminating these components may potentially improve the anti-tumor actovoty of MSHP65-TCL vaccine.

Animals ; Antigens, CD ; metabolism ; Antigens, Differentiation, T-Lymphocyte ; metabolism ; Apoptosis ; Bacterial Proteins ; administration & dosage ; immunology ; Cancer Vaccines ; Cell Extracts ; administration & dosage ; immunology ; Cell Line, Tumor ; Chaperonin 60 ; administration & dosage ; immunology ; Female ; Interferon-gamma ; metabolism ; Interleukin-10 ; metabolism ; Lectins, C-Type ; metabolism ; Melanoma, Experimental ; immunology ; pathology ; Mice ; Mice, Inbred C57BL ; Random Allocation ; Spleen ; cytology ; immunology ; metabolism ; Tumor Burden ; immunology

Parkinson′s disease is a common clinical degenerative disease of the nervous system, and rapid eye movement sleep behavior disorder (RBD) is a common sleep symptom of patients with Parkinson′s disease. This article reviews the pathogenesis, epidemiology, clinical characteristics, imaging manifestations, clinical evaluation and treatment of RBD in patients with Parkinson′s disease, in order to deepen the understanding of RBD in patients with Parkinson′s disease.

Objective To evaluate the therapeutic effect of MHSP65-TCL on melanoma and its effect on the activity of the immunocytes. Methods MHSP65-TCL was prepared by mixing MHSP65 with TCL derived from B16 melanoma cell lysate by repeated freezing and thawing. The MHSP65-TCL vaccine was administered in mice bearing B16 melanoma, and the changes in melanoma growth was observed. To investigate the influence of TCL in MHSP65-TCL on the activity of the immunocytes, we co-cultured TCL and mouse spleen cells in vitro, and analyzed CD69 expression on the cells, cell apoptosis, and levels of IL-10 and IFN-γin the cell culture supernatant. Results The MHSP65-TCL vaccine showed an anti-melanoma effect in the tumor-bearing mice. In the in vitro experiment, TCL in MHSP65-TCL strongly stimulated the activation of mouse spleen cells while causing apoptosis in some of the immunocytes and promoting cellular IL-10 secretion, but not IFN-γ. Conclusions MHSP65-TCL derived from B16 melanoma cells has an anti-melanoma effect mediated by the activation of immunocytes. TCL in MHSP65-TCL also has immunosuppressive effect on immunocytes possibly due to the presence of suppressive components in TCL, and identifying and eliminating these components may potentially improve the anti-tumor actovoty of MSHP65-TCL vaccine.

Objective To evaluate the therapeutic effect of MHSP65-TCL on melanoma and its effect on the activity of the immunocytes. Methods MHSP65-TCL was prepared by mixing MHSP65 with TCL derived from B16 melanoma cell lysate by repeated freezing and thawing. The MHSP65-TCL vaccine was administered in mice bearing B16 melanoma, and the changes in melanoma growth was observed. To investigate the influence of TCL in MHSP65-TCL on the activity of the immunocytes, we co-cultured TCL and mouse spleen cells in vitro, and analyzed CD69 expression on the cells, cell apoptosis, and levels of IL-10 and IFN-γin the cell culture supernatant. Results The MHSP65-TCL vaccine showed an anti-melanoma effect in the tumor-bearing mice. In the in vitro experiment, TCL in MHSP65-TCL strongly stimulated the activation of mouse spleen cells while causing apoptosis in some of the immunocytes and promoting cellular IL-10 secretion, but not IFN-γ. Conclusions MHSP65-TCL derived from B16 melanoma cells has an anti-melanoma effect mediated by the activation of immunocytes. TCL in MHSP65-TCL also has immunosuppressive effect on immunocytes possibly due to the presence of suppressive components in TCL, and identifying and eliminating these components may potentially improve the anti-tumor actovoty of MSHP65-TCL vaccine.

Objective This paper aims to evaluate the effectiveness of the Plan Do Check Act(PDCA)cycle in the quality improvement of medical device adverse event report forms to provide references for developing improvement strategies.Methods This study randomly selected 271 report forms from hospitals in Guangdong Province from January 1,2022,to March 31,2022 as the pre-implementation group.Another 462 report forms from January 1,2023,to March 31,2023 were randomly selected after implementing the PDCA cycle as the post-implementation group.The effect evaluation was concluded by comparing the average score on quality assessment of report forms between the two groups from 21 cities in Guangdong Province.Results The post-implementation group showed significantly higher overall average score on quality assessment as compared to the pre-im-plementation group(P＜0.05).After the implementation,the form completions on medical devices,adverse events,and usage,were significantly improved(P＜0.05).Conclusion The PDCA cycle can effectively improve the quality of medical device ad-verse event report forms,which is significant for standardizing the monitoring of medical device adverse events and subsequent in-vestigation and resolution of risk.

Objective:To investigate the application value of dual-graft living donor liver transplantation of right segment from an adult living donor combined with a left lateral segment from donation after brain death for hepatocellular carcinoma (HCC).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of a male 46-year-old patient with HCC who underwent dual-graft living donor liver transplantation of right segment from an adult living donor combined with a left lateral segment from donation after brain death at the West China Hospital of Sichuan University in October 2019 were collected. He weighed 66 kg and was 171 cm in height. His blood type was A Rh-positive. Graft one was from a female 23-year-old living donor who had a bodyweight of 50 kg, a height of 150 cm, and blood type of A Rh-positive; graft two was from a male 44-year-old brain death donor with the blood type of A Rh-positive. The surgery was performed in three operating rooms, graft one and graft two were obtained simultaneously in two operating rooms, and the recipient′s liver was dissected in the third operating room. When the in vitro splicing of the liver was almost completed, surgeons entirely removed the recipient′s liver and started to transplant the new one. Observation indicators: (1) surgical situations and postoperative recovery of the living donor and the recipient; (2) postoperative pathological examination of the recipient′s liver; (3) follow-up. Follow-up was conducted by outpatient examinations, including monitoring of HCC recurrence, monitoring of new liver function, monitoring and adjustment of immunosuppressive agents, detection of biliary vascular complications, rejection and adverse drug reactions. Regular lifelong follow-up was required for recipients, with the latest follow-up on December 4, 2019. Count data were expressed as absolute numbers or percentages.Results:(1) Surgical situations and postoperative recovery of the living donor and the recipient: operation time, volume of intraoperative blood loss, volume of intraoperative infusion of autologous blood of the living donor were 315 minutes, 200 mL, 200 mL, respectively. The living donor was discharged from hospital on the sixth day after surgery without any complications. The recipient underwent modified piggyback liver transplantation successfully. Graft one was from the right segment free of the middle hepatic vein in the living donor, with a weight of 410 g. Graft two was from the left lateral segment in the donor after brain death, with a weight of 400 g. The graft from donors to recipient weight ratio was 1.2% after splicing. The operation time, duration of anhepatic phase, volume of intraoperative blood loss, volume of intraoperative blood transfusion were 815 minutes, 60 minutes, 1 500 mL, 1 800 mL, respectively. The recipient′s temperature was normal during hospitalization. On the first postoperative day, the level of white blood cell and neutrophilic granulocyte percentage of the recipient reached a peak (17.15×10 9/L and 91.7%, respectively) and then gradually decreased. After anti-infective treatment with piperacillin sodium and sulbactam sodium, both of the two indicators returned to normal on the seventh day after surgery (7.90×10 9/L and 70.9%, respectively), and the antibiotic was discontinued. During the hospitalization, the level of albumin of the recipient fluctuated in 31.0-41.4 g/L, the liver function parameters including total bilirubin, alanine aminotransferase, aspartate aminotransferase, prothrombin time and international normalized ratio gradually returned to normal levels, and the renal function parameters including creatinine and estimated glomerular filtration rate remained within the normal range. On the tenth day after surgery, the recipient was in good condition and discharged from the hospital. (2) Postoperative pathological examination of the recipient′s liver: ① results of the pathological examination showed moderately differentiated HCC with incomplete tumour capsule and no invasion of the liver capsule. The surrounding liver tissues showed hepatitis B-related nodular cirrhosis, and no tumor involvement was detected at the broken end of the hilum. ② The gallbladder presented chronic cholecystitis accompanied by cholesterol deposition, and one abdominal lymph node showed reactive hyperplasia. The immunohistochemical staining showed 10% positive HBsAg and negative HBcAg. (3) Follow-up: the tumor markers of the recipient were tested on November 19, 2019, including α-fetoprotein (2.92 μg/L) and abnormal prothrombin (16 AU/L). Together with the negative result of abdominal colour doppler ultrasound, they collectively indicated no HCC recurrence in the recipient. The liver function parameters including total bilirubin (8.6 μmol/L), alanine aminotransferase (23 IU/L), aspartate aminotransferase (28 IU/L) and albumin (44.0 g/L) of the recipient tested on December 3, 2019, were all in normal levels. Blood concentration of tacrolimus was 4.2 μg/L . The drug dose of mycophenolate mofetil dispersible tablets was adjusted to 250 mg given twice daily, and the drug dose of others was unchanged (tacrolimus 2 mg, once daily; sirolimus 1mg, once daily). No symptoms, signs or examination results indicated biliary vascular complications, rejection or adverse drug reactions. Conclusion:Dual-graft living donor liver transplantation of right segment from an adult living donor combined with a left lateral segment from donation after brain death is safe and effective, which can be used as a suboptimal treatment for patients with HCC beyond Milan criteria.

Objective:To investigate the effects of microskin transplantation with antigen-free porcine peritoneum (AFPP) as substitutive carrier for allogeneic skin graft in treating patients with extensive deep burns.Methods:Medical records of 32 patients with extensive deep burns, hospitalized in Changhai Hospital of Naval Medical University meeting the inclusion criteria were investigated from January 2014 to December 2017. Twenty patients [12 males and 8 females, aged (35.4±2.2) years]with microskin transplantation using allogeneic skin graft as microskin carrier were included in allogeneic skin graft group and 12 patients [6 males and 6 females, aged (32.1±4.8) years] with microskin transplantation using AFPP as microskin carrier were included in AFPP group. On post injury day 3-7, the vital signs of patients were stable and escharectomy and autologous microskin grafting of head were performed. The expansion ratio of microskin, the application time of albumin and antibiotics, the percentage of infectious autologous microskin grafting area, the survival rate of microskin, and dressing change times of patients in 2 groups were recorded. Data were statistically analyzed with t test. Results:The expansion ratio of microskin of patient in AFPP group was 14.8±0.6, which was close to 13.5±0.6 of allogeneic skin graft group ( t=1.531, P>0.05). The application time of albumin and antibiotics of patients in AFPP group were close to those of allogeneic skin graft group ( t=0.027, 1.121, P>0.05). The percentage of infectious autologous microskin grafting area of patients in AFPP group was (8.5±1.2)%, which was significantly lower than (18.1±0.6)% in allogeneic skin graft group in 4 weeks after surgery( t=7.593, P<0.01), the survival rate of microskin of patients in AFPP group was (82.5±1.1)%, which was significantly higher than (72.5±0.6)% in allogeneic skin graft group ( t=8.689, P<0.01). The dressing change time of patients in AFPP group was significantly less than that in allogeneic skin graft group ( t=4.743, P<0.01). Conclusions:Compared with allogeneic skin graft, microskin transplantation with AFPP as carrier can reduce wound infection, improve the survival rate of microskin graft, and reduce dressing change time, so that AFPP is a good carrier of microskin.

Objective:To explore the mechanism of early pancreatic exocrine function changes in severely scalded rats.Methods:The experimental research methods was used. Eighty male Sprague-Dawley rats aged 7-8 weeks were divided into simple sham injury group ( n=8), sham injury+cholecystokinin octapeptide (CCK8) group ( n=8), severe scald+CCK8 group ( n=32), and extremely severe scald+CCK8 group ( n=32) by the random number table, which were treated accordingly. Immediately after injury of rats in the 2 sham injury groups and 1, 2, 3, and 7 days after injury of rats in the 2 scald groups, the improved methods including pancreatic duct puncture and catheterization were used to dynamically collect the pancreatic-bile juice (PBJ) of rats. The PBJ secretory volume within 1 h was recorded, and the content of pancreatic lipase, α-amylase, and trypsin in PBJ was detected by enzyme-linked immunosorbent assay (ELISA), and the number of samples was 8. The femoral venous blood was collected, and the concentrations of pancreatic lipase and α-amylase in serum were detected by standard colorimetry to reflect their activity ( n=8). The pancreatic tissue was extracted, and the levels of interleukin-1β (IL-1β) and IL-6 in pancreatic tissue were detected by ELISA ( n=8), the expression of hypoxia-inducible factor 1α (HIF-1α) in pancreatic tissue was detected by immunofluorescence method, and the histopathological changes in pancreatic tissue were observed by hematoxylin-eosin staining, the severity of pancreatic tissue injury in the 2 scald groups was evaluated by modified Schmidt method ( n=6), and the ultrastructure of acinar cells in pancreatic tissue was observed by transmission electron microscopy. Data were statistically analyzed with analysis of variance for factorial design, Tukey test, independent sample t test, and least significant difference test. Results:Compared with the PBJ secretory volume (0.740±0.030) mL in the pancreatic tissue of rats in simple sham injury group within 1 h immediately after injury, the (0.823±0.033) mL in sham injury+CCK8 group was significantly increased ( t=4.92, P<0.05). Compared with that of rats in sham injury+CCK8 group immediately after injury, the PBJ secretory volume of rats within 1 h in severe scald+CCK8 group ((0.681±0.024), (0.608±0.056), (0.525±0.025), and (0.720±0.044) mL) and extremely severe scald+CCK8 group ((0.540±0.025), (0.406±0.021), (0.475±0.036), and (0.690±0.018) mL) was significantly decreased on 1, 2, 3, and 7 days after injury ( P<0.05). Compared with that in severe scald+CCK8 group, the PBJ secretory volume of rats within 1 h in extremely severe scald+CCK8 group was significantly decreased on 1 and 2 days after injury ( P<0.05). Compared with that of rats in simple sham injury group immediately after injury, the content of pancreatic lipase, α-amylase, and trypsin in PBJ of rats in sham injury+CCK8 group immediately after injury was significantly increased (with t values of 4.56, 3.30, and 4.99, respectively, P<0.05). Compared with that of rats in sham injury+CCK8 group immediately after injury, the content of pancreatic lipase and α-amylase in PBJ of rats in severe scald+CCK8 group and extremely severe scald+CCK8 group was significantly decreased on 1, 2, 3, and 7 days after injury ( P<0.05), the trypsin content in PBJ of rats in extremely severe scald+CCK8 group was significantly decreased on 2 days after injury ( P<0.05). Compared with that in severe scald+CCK8 group, the content of pancreatic lipase in PBJ of rats in extremely severe scald+CCK8 group was significantly decreased on 1, 2, and 3 days after injury ( P<0.05), and the content of α-amylase and trypsin in PBJ was significantly decreased on 1 and 2 days after injury ( P<0.05). There were no statistically significant differences in the activities of pancreatic lipase and α-amylase in serum of rats among the 4 groups at various time points after injury ( P>0.05). Compared with that of rats in sham injury+CCK8 group immediately after injury, the levels of IL-1β in pancreatic tissue of rats in severe scald+CCK8 group on 1, 2, and 3 days after injury and in extremely severe scald+CCK8 group on 1, 2, 3, and 7 days after injury were significantly increased ( P<0.05), and the levels of IL-6 in pancreatic tissue of rats in severe scald+CCK8 group and extremely severe scald+CCK8 group were significantly increased on 1, 2, 3, and 7 days after injury ( P<0.05). Compared with that in severe scald+CCK8 group, the IL-1β level in pancreatic tissue of rats in extremely severe scald+CCK8 group was significantly increased on 2 and 3 days after injury ( P<0.05), and IL-6 level in pancreatic tissue was significantly increased on 2 days after injury ( P<0.05). The expression levels of HIF-1α in pancreatic tissue of rats in simple sham injury group and sham injury+CCK8 group immediately after injury were lower; and compared with that in sham injury+CCK8 group immediately after injury, the expression levels of HIF-1α in pancreatic tissue of rats in the 2 scald groups increased to a certain extent at different time points after injury, and the expression position was transited from the edge of the pancreatic tissue to the whole pancreas, the expression levels of HIF-1α in pancreatic tissue of rats in the 2 scald groups tended to be normal on 7 days after injury. Compared with that in simple sham injury group immediately after injury, the proportion of acinar cell cytoplasm in pancreatic tissue of rats in sham injury+CCK8 group was increased; and with the increase of time after injury, edema, hemorrhage, necrosis, and inflammatory infiltration appeared in pancreatic tissue of rats in the 2 scald groups. Compared with that in severe scald+CCK8 group, the scores of edema, inflammatory cell infiltration, bleeding, and necrosis in pancreatic tissue of rats in extremely severe scald+CCK8 group were increased to varying degrees at various time points after injury, and the scores of pancreatic tissue of rats in the 2 scald groups basically recovered to normal on 7 days after injury. Compared with that in simple sham injury group immediately after injury, the number of enzyme granules in acinar cells of pancreatic tissue of rats in sham injury+CCK8 group was increased, and with the increase of time after injury, the enzyme granules in acinar cells of rats in the 2 scald groups were gradually reduced basically. Conclusions:The exocrine functions of pancreas, such as synthesis and secretion of pancreatic enzymes, are decreased in the early stage in severely scalded rats. And the greater the scalded area, the more significant the decline of pancreatic exocrine function. This change may be related to hypoxic injury and inflammation in pancreatic tissue after severe scald.