Objective To explore the effects of botulinum toxin type A (BTX-A) on the F-waves of the tibial nerve and the walking ability of stroke patients.Methods Twenty stroke patients with spastic hemiplegia of a lower limb were randomly divided into experimental and control groups with 10 patients in each group.All received four weeks of conventional rehabilitation,including walking training,balance training and muscle strength training.In the experimental group,a total of 300 IU of BTX-A was injected into the gastrocnemius (200 IU) and soleus muscles (100 IU)before the start of routine rehabilitation,guided by using the electrical stimulation.Muscle tone was assessed using the modified Ashworth scale(MAS).Walking ability was assessed with the timed up and go test (TUGT) and a 10 m free walking test.F-wave parameters were recorded in the tibial nerve before,two weeks and four weeks after the injection.Results In the experimental group there was a significant difference in F-wave amplitude between those recorded before treatment and after two weeks of treatment.The control group showed no statistically significant difference.In experimental group there was also a statistically significant difference in triceps muscle tension before and after treatment which was not observed in the control group.Walking ability improved significantly in both groups.Conclusions Local injection of BTX-A into the lower limbs can reduce the F-wave amplitudes of spinal cord motor neurons.BTX-A injection combined with rehabilitation training can significantly improve the walking ability of stroke patients.

Objective To explore any effect of proprioceptive neuromuscular facilitation (PNF) on the proprioception and balance of patients with knee osteoarthritis (KOA).Methods Forty patients with KOA were randomly divided into an experimental group (EG) and a control group (CG),each of 20.The PNF techniques of isotonic combined contraction,and rhythmic stable and dynamic reversal were applied in the EG,while the CG received quadriceps muscle strength training.Knee proprioception was evaluated using knee angle reconstruction experiments,and balance ability was measured using the one leg standing test (OLS) and the five times sit to stand test (FTSST).Results The errors in active and passive knee angle reconstruction at 30°,60° and 110° all improved significantly in the EG,but not in the CG.After the treatment,the OLS and FTSST results improved significantly in the EG,but only the OLS results improved significantly in the CG,not the FTSST times.Even so,the average OLS time in the EG was significantly longer than that of the CG after the training.Conclusion Proprioceptive neuromuscular facilitation can improve the proprioception and balance of persons with knee osteoarthritis.

Objective To investigate the effect of PBL method in the pathogen and immunology teaching. Methods PBL teaching was practised in trial group,while LBL teaching was practiced in control group.The writers made an analysis of this teaching by way of questionnaire and exam. Results Many students by PBL teaching accept PBL teaching Method,and improve their self-study ability,understanding ability,analyzing ability and so on. Conclusion PBL teaching method is much better than LBL teaching method,and can improve the quality of pathogen and immunology teaching.

Objective To study the effects of compound preparations which contain docosahexenoic acid (DHA),soybean lecithin,and vitamin A on memory ability of children and to compare the difference between two compound preparations that contain DHA from marine algae and from fish oil.Methods Totally 160 11-12-year-old healthy children who were studying in a primary school in Baoshan District of Shanghai were enrolled in this study.All the subjects signed the informed consent form.Subjects were randomly divided into three groups with random numbers:marine algae DHA group(n=53),fish oil DHA group(n=53),and control group(n=54).Subjects in the marine algae DHA group were given compound preparation which contained DHA form marine algae,soybean lecithin,and vitamin A;subjects in fish oil DHA group were given compound preparation which contained DHA form fish oil,soybean lecithin,and vitamin A.The dose of DHA(200 mg DHA per capsule)and other components in the two groups was equal.Subjects in the control group were given a placebo with same appearance.The trial lasted 30 days.Each subject took a capsule per day.Immediately before and after the trial,subjects were tested by using the clinical memory scale compiled by the Institute of Clinical Psychology of the Chinese Academy of Sciences.Results Before the trial.there was no difference amongthree groups in terms of all items of clinical memory scale or memory quotient(all P>0.05).After the trial,except for associative learning(both P>0.05),the other items of the clinical memory scale and memory quotient in both marine algae DHA group and fish oil DHA group were significantly higher than those of control group(all P<0.05).No significant difference was noted between the marine algae DHA group and fish oil DHA group for all items of the clinical memory scale or memory quotient(all P>0.05).Conclusions DHA compounds can impreve the memory ability of children.DHAs with different sources have similar effect on memory ability.

Objective To analyze the distribution and antimicrobial resistance situation of pathogens isolated from blood culture to provide the scientific basis for the accuratel use of antibacterial drugs and preventing and controlling nosocomial acquired blood‐stream infection .Methods The US BACTEK‐FK automatic blood culture instrument and the French VITEK 2 COMPACT auto‐matic bacteria identification/susceptibility system were used to conduct the culture ,identification of blood culture isolated bacterial strains and drug susceptibility test .The results of drug susceptibility test were judged by adopting the 2011 criteria of the Clinical Laboratory and Standards Institute(CLSI) .Results The main isolated bacteria from blood culture for the recent three years were E coli ,staphylococcus aureus and klebsiella pneumonia bacteria ,coagulase negative staphylococcus(CNS) ,etc .The proportions of hos‐pital‐acquired bloodstream infections during these period were 42 .2% ,46 .9% and 54 .1% respectively .The detection rate of methi‐cillin‐resistant staphylococcus aureus (MRSA) was 18 .8% ,which of multiple drug resistant acinetobacter baumannii (MDRAB) was 42 .9% ,which of producing extended spectrum beta lactamase (ESBLs) in E .coli and klebsiella pneumoniae were 71 .8% and 69 .8% respectively .Conclusion The bloodstream infections pathogens in this hospital are mainly Enterobacteriaceae bacteria ,the proportion of hospital‐acquired bloodstream infections increases year by year ;the detection rate of multi‐drug resistant Acinetobact‐er baumanni (MDRAB) is higher ,clinic should pay more attention to the change of blood culture pathogens and their drug resist‐ance trend ,meanwhile nosocomial bloodstream infection should be prevented and controlled .

Objective: To investigate the clinical significance of tumor associated macrophages (TAM) in multiple myeloma (MM) and the relationship with angiogenesis and immunosuppression. Methods: Seventy cases of MM patients diagnosed from August 2015 to June 2017 were enrolled in the study as experimental group, 20 cases of benign hematological diseases (13 with iron deficiency anemia and 7 with megaloblastic anemia) patients as control group. Immunohistochemical method was used to detect the expression of CD163, CD34 and VEGF in bone marrow samples, and flow cytometry was used to detect the proportion of regulatory T cell (Treg cells), ELISA was used to detect the level of IL-10, and the clinical features were analyzed. Results: ①Among the 70 patients, there were 31 males and 39 females with a median age of 65 (50~78) years old. TAM infiltration density, microvascular density (MVD), VEGF expression level, Treg ratio and IL-10 level in bone marrow samples of 70 MM patients were significantly higher than those of benign hematological diseases (P<0.05). ②In the MM group, the above indexes of the patients with disease stabilized (15 cases) were lower than those of the newly diagnosed group (35 cases) and the relapse refractory group (20 cases) (P<0.05), those of relapse refractory group were higher than those of newly diagnosed group (P>0.05). ③Of the 35 newly diagnosed MM patients, 27 completed 4 courses of treatment. In the effective group (15 cases), the TAM infiltration density after treatment was significantly lower than that before treatment, the difference was statistically significant[(20.20±7.66) vs (28.87±11.97), t=2.362, P=0.025]; while in the ineffective group of 12 cases, the difference of the TAM infiltration density before and after treatment was not statistically significant[(42.00±13.76) vs (48.25±13.59), t=1.119, P=0.275]. ④TAM infiltration density in the effective group after bortezomib treatment (21 cases) were lower than those in the non-bortezomib treatment group (18 cases)[(16.52 ±4.26) vs (19.27 ±5.82), t=1.662, P=0.170]. ⑤The TAM infiltration density in MM patients was positively correlated with MVD, VEGF expression level, Treg cell ratio and IL-10 level (P<0.001). Conclusion The infiltration of TAM in the microenvironment of MM, which may promoting angiogenesis and inhibiting immune response, is related to the occurrence, development, therapeutic effect and drug resistance of MM.

Objective: To analyze the detection rate of sleep problems such as sleep delay and deficiency in preschool children in the middle and lower reaches of the Yangtze River in China,and to provide the reference for the standard of sleeping mode among preschool students. Methods: From October to November 2017, a questionnaire survey was conducted among 27 200 preschool children in 11 cities in Hubei, Anhui and Jiangsu provinces in the middle and lower reaches of the Yangtze River in China. Epidemiology of sleep delays, deficiencies and sleep patterns in preschool children was described. Results: The detection rate of sleep problems in preschool children in the middle and lower reaches of the Yangtze River was 15.3%. Taking the length of sleep and bedtime as the main analysis points, it was found that the average sleeping time point of each age group was 21:31, and the detection rate of bedtime delay was 86.5%. The average length of sleep was (10.60±1.12) hours. The detection rate of sleep deprivation in preschool children was 15.7%. Sleep delay was positively correlated with girls, age increase and parents’ higher educational level (P<0.05), and negatively correlated with living in the city, non-only child and bedroom without TV (P<0.01) .The detection rate of sleep deprivation was positively correlated with children of high age group (4yearold group：OR=1.32，95%CI=1.19-1.46；5-year-old group：OR=2.10，95%CI=1.91-2.32；6-year-old group：OR=2.47，95%CI=2.20-2.77)(P<0.01), and negatively correlated with no TV in bedroom (OR=0.91，95%CI=0.84-0.98) and no light in sleep (OR=0.87，95%CI=0.78-0.97)(P<0.05). Conclusion Preschool children sleep delay and sleep deprivation and other sleep problems are more prominent, affected by family environment and other factors.

Objective:To explore the safety and efficacy of chimeric antigen receptor T-cell (CAR-T) therapy for relapsed/refractory acute B-cell lymphoblastic leukemia (B-ALL) with T315I mutation.Methods:The clinical data of a patient with relapsed/refractory B-ALL with T315I mutation who underwent CAR-T therapy in the Second Affiliated Hospital of Anhui Medical University was analyzed, and the related literature was reviewed.Results:The patient was a 34-year-old man. He was diagnosed with chronic myelogenous leukemia (CML) in January 2017 and started to take imatinib orally. However, the primary affection transformed to B-ALL 4 months later. Because of the E355G gene mutation, the treatment drug was adjusted to dasatinib, and induction chemotherapy was given at the same time. The sequential consolidation chemotherapy was given for 3 times after complete remission (CR). After half a year of remission, T315I mutation was detected and re-induced chemotherapy was given, but ineffective. The patient was treated with CAR-T 3 days after FC regimen (fludarabine 30 mg/m 2 per day, day 1 to day 3; cyclophosphamide 200 mg/m 2, day 1 to day 3). The number of CD19 CAR-T was 1.0×10 9, 98% activity degree. Grade 1 cytokine-releasing syndrome appeared after infusion, and was resolved after symptomatic treatment. No serious adverse reactions were observed. CR was achieved half-month after CAR-T treatment, and umbilical cord blood transplantation was successfully performed 1 month later. At the last follow-up, the relapse-free survival time of the patient was 396 days. Conclusion:CAR-T therapy may be a new, safe and effective therapy for patients with relapsed/refractory B-ALL with T315I mutation.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

ObjectiveTo explore the effect of Xianlian Jiedu prescription （XLJDP） on the proliferation and glycolysis of human colorectal cancer HCT-116 cells and the underlying mechanism. MethodHCT-116 cells were cultured with XLJDP and then the survival rate was examined by methyl thiazolyl tetrazolium （MTT） assay. The effect on the HCT116 cell proliferation was detected by colony formation assay and 5-ethynyl-2′-deoxyuridine （EDU） incorporation assay. The amount of glucose consumed by HCT-116 cells was measured by glucose test kit， and the amount of produced lactic acid was determined by lactic acid test kit 48 h after the treatment with XLJDP. The expression of glycolysis-related proteins mammalian target of rapamycin （mTOR）， phosphorylated mTOR （p-mTOR）， glucose transporter 1 （GLUT1）， and lactate dehydrogenase （LDHA） was detected by Western blot. ResultThe half-maximal inhibitory concentration （IC₅₀） of XLJDP against HCT-116 cells was 6.82 g·L^-1. Compared with the blank group， XLJDP （1.625， 3.25， 6.50 g·L^-1） inhibited the proliferation of HCT-116 cells （P<0.05， P<0.01）. Moreover， compared with the blank group， XLJDP （1.625， 3.25， 6.50 g·L^-1） suppressed glucose uptake and lactic acid production in a dose-dependent manner （P<0.05， P<0.01）. The expression of p-mTOR/mTOR， LDHA， and GLUT1 was down-regulated by XLJDP （P<0.05， P<0.01）. ConclusionXLJDP can significantly inhibit the proliferation and the Warburg effect of glycolysis in colorectal cancer cells by regulating the mTOR signaling pathway and the down-regulating the expression of LDHA， GLUT1， and other key proteins and enzymes in glycolysis.