Objective To investigate the effects of the polymer pharmaceutical excipient methoxy poly-ethylene glycol poly-lactic acid(mPEG-PLA)in Sprague-Dawley(SD)rats and Beagle dogs and its toxicological reactions,to provide a reference for its safe clinical use.Methods SD rats and Beagle dogs(male∶female ratios,1∶1)were divided randomly into control group and low,medium,and high dose mPEG-PLA groups(70,210,700 mg/kg).Animals received intravenous mPEG-PLA once a day for 90 days,followed by a 28-day recovery period.Indicators including clinical observations,food intake,body weight,hematology,blood biochemistry,immune function,and pathological examination were recorded.Results Compared with the control group,(1)food intake was decreased(P＜0.01)and body weight was increased(P＜0.05 or P＜0.01)after 90 days of continuous administration,with similar changes in the medium and high dose groups in both rats and dogs.In addition,MONO/MONO％,RBC,MCH,MCHC,HCT,HGB,PLT,TP,ALB,GLB,and Fbg were all decreased(P＜0.05 or P＜0.01)and coagulation indexes(e.g.,APTT)were increased(P＜0.05 or P＜0.01).Organ weights and the organ-to-body/brain weight ratios of the liver and spleen were increased(P＜0.05 or P＜0.01),and histopathology indicated numerous foam-like macrophages in the hepatic sinuses,red spleen pulp,and lymph node medulla.DBIL and TBIL also increased in rats in the high dose group(P＜0.05 or P＜0.01),while the dogs experienced skin swelling or scabs,abdominal swelling,vomiting,decreased activity,high albuminuria,and ascites,and the renal glomerular cells showed vacuoles.(2)After 28 days of recovery,rats and dogs in the medium and high dose groups showed a few foam-like macrophages in the hepatic sinuses,red spleen pulp,and lymph node medulla,as well as decreased of food intake in dogs.The MCHC,PLT,and TP decreased in dogs in the high dose group(P＜0.05),and the liver and spleen weights and organ coefficients in rats increased(P＜0.05 or P＜0.01),while the MONO％decreased in male rats in the medium dose group(P＜0.05).Conclusions Administration of mPEG-PLA 210 and 700 mg/kg for 90 days caused blood mononuclear cells to enter and aggregate in the liver,spleen,lymph nodes,and other tissues in SD rats and Beagle dogs,leading to secondary tissue structural damage.Protein and fibrinogen synthesis and bilirubin metabolism in the liver decreased,leading to abnormal coagulation function,and decreased intravascular colloid osmotic pressure resulted in edema and bleeding.The result suggest that the liver,spleen,kidney,and lymph nodes are target organs for mPEG-PLA toxicity,with dose-dependent and reversible effects and species differences,but no significant sex differences.Clinical monitoring of related organ functions is needed to avoid secondary damage.

Objective:To discuss the relationship between Msh homeobox 1(MSX1)gene methylation and the clinicopathological characteristics and prognosis of the patients with cervical cancer(CC),and to analyze the application prospect of MSX1 gene methylation in the diagnosis and treatment of CC.Methods:The clinical data,cancer tissues,and adjacent normal tissues were collected from 120 CC patients who underwent surgery between January 2019 and June 2020,and all CC patients were followed up for 3 years;methylation-specific PCR(MSP)was used to detect the methylation status of the MSX1 gene in cancer tissues of the CC patients,who were divided into MSX1 gene hypo-methylation group(n=50)and MSX1 gene hyper-methylation group(n=70);MSP was used to detect the methylation level of the MSX1 gene in cancer tissues of the CC patients,and the relationship between MSX1 gene methylation status and clinicopathological characteristics and prognosis of the CC patients was analyzed;Western blotting method was used to detect the expression level of MSX1 protein in cancer tissues and adjacent normal tissues of the CC patients;small interfering RNA(siRNA)targeting MSX1 mRNA was designed;the CC cells were divided into control group(transfected with blank vector)and siMSX1 group(transfected with MSX1 siRNA);real-time fluorescence quantitative PCR(RT-qPCR)method was used to verify the cell transfection efficiency;cell scratch assay was used to detect the migration activity of the cells in two groups;Logistic regression was used to analyze the influencing factors of prognosis in the CC patients.Results:The methylation rate in cancer tissues of the CC patients was 58.33%,which was significantly higher than that in adjacent normal tissues(11.67%,χ2=42.725,P<0.01);the Western blotting results showed that compared with adjacent normal tissue,the expression level of MSX1 protein in cancer tissue of the CC patients was significantly decreased(P<0.01);high methylation status of the MSX1 gene in cancer tissue of the CC patients was associated with high-risk human papillomavirus(HR-HPV)DNA,lymph node metastasis,and TNM stage(P<0.05),but not associated with patient age,pathological type,and tumor size(P>0.05);the cell scratch assay results showed that compared with control group,the expression level of MSX1 mRNA in the cells in siMSX1 group was significantly decreased(P<0.01),suggesting successful knockout of the MSX1 gene;the cell scratch assay results showed that compared with control group,the migration activity of the cells in siMSX1 group was significantly increased(P<0.01);the 3-year cumulative survival rate of patients with MSX1 gene methylation was 54.29%,which was significantly lower than that of patients without MSX1 gene methylation(80.00%,χ2=9.717,P=0.002);the Logistic regression results showed that positive HR-HPV DNA,lymph node metastasis,TNM stage Ⅲ-Ⅳand MSX1 gene high methylation were independent risk factors for prognosis in CC patients(P<0.05).Conclusion:MSX1 gene methylation is associated with poorer clinicopathological characteristics and adverse prognosis in the CC patients,suggesting its potential as a biomarker for cervical cancer.

Objective To investigate the effects of the polymer pharmaceutical excipient methoxy poly-ethylene glycol poly-lactic acid(mPEG-PLA)in Sprague-Dawley(SD)rats and Beagle dogs and its toxicological reactions,to provide a reference for its safe clinical use.Methods SD rats and Beagle dogs(male∶female ratios,1∶1)were divided randomly into control group and low,medium,and high dose mPEG-PLA groups(70,210,700 mg/kg).Animals received intravenous mPEG-PLA once a day for 90 days,followed by a 28-day recovery period.Indicators including clinical observations,food intake,body weight,hematology,blood biochemistry,immune function,and pathological examination were recorded.Results Compared with the control group,(1)food intake was decreased(P＜0.01)and body weight was increased(P＜0.05 or P＜0.01)after 90 days of continuous administration,with similar changes in the medium and high dose groups in both rats and dogs.In addition,MONO/MONO％,RBC,MCH,MCHC,HCT,HGB,PLT,TP,ALB,GLB,and Fbg were all decreased(P＜0.05 or P＜0.01)and coagulation indexes(e.g.,APTT)were increased(P＜0.05 or P＜0.01).Organ weights and the organ-to-body/brain weight ratios of the liver and spleen were increased(P＜0.05 or P＜0.01),and histopathology indicated numerous foam-like macrophages in the hepatic sinuses,red spleen pulp,and lymph node medulla.DBIL and TBIL also increased in rats in the high dose group(P＜0.05 or P＜0.01),while the dogs experienced skin swelling or scabs,abdominal swelling,vomiting,decreased activity,high albuminuria,and ascites,and the renal glomerular cells showed vacuoles.(2)After 28 days of recovery,rats and dogs in the medium and high dose groups showed a few foam-like macrophages in the hepatic sinuses,red spleen pulp,and lymph node medulla,as well as decreased of food intake in dogs.The MCHC,PLT,and TP decreased in dogs in the high dose group(P＜0.05),and the liver and spleen weights and organ coefficients in rats increased(P＜0.05 or P＜0.01),while the MONO％decreased in male rats in the medium dose group(P＜0.05).Conclusions Administration of mPEG-PLA 210 and 700 mg/kg for 90 days caused blood mononuclear cells to enter and aggregate in the liver,spleen,lymph nodes,and other tissues in SD rats and Beagle dogs,leading to secondary tissue structural damage.Protein and fibrinogen synthesis and bilirubin metabolism in the liver decreased,leading to abnormal coagulation function,and decreased intravascular colloid osmotic pressure resulted in edema and bleeding.The result suggest that the liver,spleen,kidney,and lymph nodes are target organs for mPEG-PLA toxicity,with dose-dependent and reversible effects and species differences,but no significant sex differences.Clinical monitoring of related organ functions is needed to avoid secondary damage.

Objective:To explore the effects of personalized home rehabilitation nursing guided by professionals in children with autism spectrum disorder.Methods:From January 2019 to January 2021, 60 children with autism spectrum disorder who were followed up and diagnosed and their parents in the Department of Child Psychology at Hangzhou Seventh People's Hospital were selected as the research subject. The children and their parents were divided into a study group and a control group using a random number table method, with 30 cases in each group. The parents of the control group received theoretical training on autism spectrum disorder, while the parents of the study group received personalized home rehabilitation nursing guided by professional nursing staff. The intervention period was four weeks. Two groups of children were evaluated for autism using the Autism Behavior Checklist (ABC) Scale and the Childhood Autism Rating Scale (CARS) .Results:Before intervention, there was no statistically significant difference in the total score and dimension scores of ABC Scale between the two groups of children ( P>0.05). After intervention, the total score of ABC Scale, physical movement and language scores of the study group were lower than those of the control group, with statistically significant differences ( P<0.05). Before intervention, there was no statistically significant difference in CARS scores between the two groups of children ( P>0.05). After intervention, the CARS score of the study group was lower than that of the control group, with statistically significant difference ( P<0.05) . Conclusions:The personalized home rehabilitation nursing under the guidance of professionals in children with autism spectrum disorder shows good outcomes, which can effectively improve the clinical symptoms and behaviors of children.

Objective:To explore the regional brain activities in healthy adolescent subjects after sleep deprivation (SD) using amplitude of low-frequency fluctuation (ALFF) method.Methods:Total of 16 healthy adolescent subjects (8 males,8 females;aged 13-20 years) were recruited in the community and the campus through the internet and posters.Each of the 16 healthy adolescent subject underwent the attention network test and magnetic resonance imaging (MRI) session twice:once was after rested wakefulness (RW condition),and the other was after SD condition.Amplitude of low frequency fluctuation (ALFF) method was used to assess the local brain features.The mean ALFF signal values of the different brain areas were performed to investigate their relationships with the accuracy rate,reaction time and lapse rate in the attention network test,and were analyzed with a receiver operating characteristic (ROC) curve to investigate their sensitivities and specificities to distinguish the SD condition from the RW condition.Results:Subjects showed a lower response accuracy rate [(83 ± 12) ％ vs.(97 ± 4) ％,P ＜ 0.05],a longer response time [(832 ± 134) ms vs.(715 ± 97) ms,P ＜ 0.05] and a higher lapse rate [(15 ± 11)％ vs.(2.4 ±7.3)％,P ＜0.05] under SD condition than under RW condition.They showed higher ALFF area in the right cuneus (BA 17,BA 18),and lower ALFF areas in the right lentiform nucleus,right claustrum,left dorsolateral prefrontal cortex (BA 46) and left inferior parietal cortex (BA 39) under SD condition than under RW condition.Under SD condition,the mean ALFF signal value of the right claustrum showed a significant positive correlation with the accuracy rate (r =0.69,P ＜0.05),and a negative correlation with the lapse rate (r =-0.71,P ＜0.05).The mean ALFF signal value of the dorsolateral prefrontal cortex showed a significant positive correlation with the reaction time (r =0.68,P ＜ 0.05).The values of area under the curve of the right cuneus,right lentiform nucleus,right claustrum,left dorsolateral prefrontal cortex and left inferior parietal cortice were 0.9,0.8,0.9,0.8 and 0.9,respectively.These different ALFF areas also showed high degree of sensitivities and specificities.Conclusion:Sleep deprivation leads to the dysfunction in the default mode network,anticorrelatedtask-positive network,and advanced cognitive function brain areas,and the functional compensation in the visual network.

Objective To observe the effect of compound iodine alcohol skin disinfectant heated to 40℃using among operation patients .Methods 100 operation patients were randomly divided into two groups:the test group (n=50 cases, accepting heated Anerdian) and the control group (n=50 cases, accepting no heated Anerdian ) .Effectiveness of the iodine content , alcohol content , of bacterial culture and the rate of chill were compared between the two groups .Results In the test group accepting heated Anerdian , the effectiveness of the iodine content was (0.102 ±0.0015)%(g/ml), the effectiveness of the alcohol content was (68.1 ± 1.54)%(g/ml).The differences were significant (t =-12.88, -4.594, respectively;P <0.05).No bacterial culture of the skin sample had been found between the two groups .10min after the sterilization, 4.0%patients in the test group and 24.0%patients in the control group had chill .There was a significant difference between groups (χ2 =8.306,P<0.01).Conclusions Compound iodine alcohol skin disinfectant heated to 40℃can conveniently and effectively increase the degree of comfort of the operation patients .

Objective To explore the effrciency of intra-arterial neoadjuvant chemotherapy before radical excision in patients with cervical cancer.Methods 50 cases with cervical cancer were enrolled into the study and were treated with a 2～3 course of intra-arterial neoadjuvant chemotherapy immediately after the pathological diagnosis.The regime included Then radical excision was performed in those who were good for the operation.Results Complete recovery(CR) was acquired in 12 patients and partial recovery(PR) in 26 patients.The total response rate was 76.0 %.The tumor size reduced significantly(P

Objective To study the influence factor of recurrence in breast cancer.Methods The grouping treatment and tumor by stages,tumor transfer were observed in 105 cases with primary breast cancer.Results Among 105 patients,the inside of 2 years relapse was 47.6%(50/105);Tumor Ⅱ period recurrence rate was 40.0%(10/25),Ⅲ period recurrence rate was 28.0%(7/25);Among 105 cases,the distant place transfer to recurrence rate was 31.4%(33/105);Among 105 patients for surgical operation,its relapsing rate was 40.0%,but in 25 cases after operation putting radiation treatment,relapse rate was 16.0%;The part recurrence rate totally was 58.0%(61/105),among them the chest wall recurrence rate was 13.3%(14/105);The supraclavilar lymphonodes transfer was 20.9%(22/105),the axlla lymphnides transfer was 23.8%(25/105);The distant place transfer was 31.4%(33/105).Conclusion The recurrence rate of association treatment obviously is lower than that pure surgical operation,the relapsing of tumor with tumor by stages and transfer relevanted.