Objective:To evaluate the clinical efficacy and safety of Blinatumomab on the treatment of refractory or relapsed precursor B-cell acute lymphoblastic leukemia (R/R BCP-ALL) in children.Methods:Clinical data of children with R/R BCP-ALL treated with Blinatumomab in the Department of Hematology, Children′s Hospital of Soochow University, from August 2021 to June 2022 were retrospectively analyzed.Children were divided into<45 kg group and ≥45 kg group according to their weight at admission.They were treated with different dosages of Blinatumomab, and bone marrow remission was assessed at about 15 days.Clinical indicators and adverse events during the treatment period were recorded.The rank sum test of two independent samples were used to compare the differences between groups.The Fisher′ s test was used for comparing categorical variables. Results:Among the 16 children with R/R BCP-ALL, 12 cases (75%) achieved complete response (CR) and minimal residual lesion (MRD) turned negative at about 14 days.Among them, 5 out of 9 children with bone marrow primitive naive cell ratio≥0.5 achieved CR, and 7/7 children with bone marrow primitive naive cell ratio<0.5 achieved CR.The peak value of interleukin-6 (IL-6) in children with CR was significantly higher than those without CR ( Z=2.50, P=0.012). Twelve cases achieved CR on bone marrow assessment around day 15, and 3 cases who did not achieve CR remained in remission on day 28, with an efficacy prediction accuracy of 93.8%(15/16). Adverse events included fever, neutropenia, hypokalemia, abnormal liver function, hypocalcemia, edema, rash, hypertension, myocardial damage, abdominal pain, hypotension, and cytokine release syndrome, which were all grade 1.Neurotoxicity and death were not reported. Conclusions:The remission rate of R/R BCP-ALL in children treated with Blinatumomab was high, especially in patients with a low tumor load.The toxicity and adverse events of Blinatumomab treatment are minor and controllable.Day 15 is the optimal time point to evaluate the efficacy of Blinatumomab on children with R/R BCP-ALL, and a higher IL-6 peak can be served as a predictor of its efficacy.

Objective:To evaluate the effect of dual-tube epidural segmental injection of lidocaine analgesia on the delivery outcome and maternal and infant complications of persistent posterior occipital position postpartum or lateral occipital position postpartum patients with protracted active phase.Methods:The full and single-term primiparas ( n=216, 37 to 42 weeks gestation, 22 to 35 years) diagnosed as persistent posterior or lateral occipital position during the active period were selected from the Department of Obstetrics of Qingdao Municipal Hospital from January 2015 to October 2019. The subjects were randomly assigned into two groups: double-tube epidural block group ( n=108) and single-tube epidural block group ( n=108), 1% lidocaine was used for epidural analgesia respectively under ultrasound guidance. Senior midwife or obstetricians implement new partogram, and guide women to perform position management, and push or rotate the fetal head in a timely manner. Observation indicators: general condition, the use of non-pharmacological analgesic measures, analgesia related conditions and pain visual analogue scale (VAS) score, delivery-related indicator, cesarean section indication, anesthesia-related indicator, maternal and child complications. Results:(1) General condition: the age, weight, height, gestational age, the ratio of persistent lateral or posterior occipital position, cephalic score, and neonatal birth weight between the two groups of women were not statistically significant (all P>0.05). (2) The use of non-pharmacological analgesic measures: the women’s Lamaze breathing method, Doula delivery companionship, percutaneous electrical stimulation, and other measures between two groups were compared, and there were not significant differences (all P>0.05). (3) Analgesia related conditions and VAS scores of women undergoing vaginal delivery: compared with the single-tube epidural block group ( n=40), the second-partum time of the women in the double-tube epidural block group ( n=59) was significantly shortened [(124±44) vs (86±33) minutes, P<0.01]; after 30 minutes of analgesia (4.4±0.5 vs 0.9±0.5, P<0.01), during forced labor in the second stage of labor (5.7±0.6 vs 1.3±0.4, P<0.01), the VAS scores of pain were also significantly reduced ( P<0.01). (4) Labor-related indicators: compared with the single-tube epidural block group, the natural delivery rate (21.3% vs 49.1%) and the delivery experience satisfaction rate (51.9% vs 98.1%) of women in the double-tube epidural block group were significantly increased (all P<0.01), cesarean section rate (63.0% vs 45.4%), instrument assisted rate (15.7% vs 5.6%) decreased significantly (all P<0.05). (5) Cesarean section indications: compared with the single-tube epidural block group, the cesarean section rate caused by prolonged labor or protracted active phase of women in the double-tube epidural block group was significantly reduced (38.0% vs 22.2%； P<0.05), and the fetal distress, intrauterine infection, and social factors caused by cesarean section between the two groups were compared, while the differences were not statistically significant (all P>0.05).(6) Anesthesia related indexes: the block planes of the maternal upper tube administration in the double-tube epidural block group were mostly T7, T8, T9-L2 and L3,While,the block planes in the single-tube epidural block group were mostly T10, T11-S1, S2, S3, and the modified Bromage score were all 0. (7) Maternal and child complications: compared with the single-tube epidural block group, the postpartum hemorrhage rate (18.5% vs 7.4%), the perineal lateral cut rate (20.4% vs 5.6%), the neonatal asphyxia rate (12.0% vs 3.7%), ICU rate of transferred neonates (13.9% vs 4.6%) in the double-tube epidural block group were significantly reduced (all P<0.05). Soft birth canal injury rate, puerperal disease rate and neonatal birth rate between two groups were compared, and there were not statistically significant differences (all P>0.05). Conclusion:Dual-tube epidural segmental injection of lidocaine analgesia could increase the natural delivery rate of women with posterior occipital or lateral occipital position with active stagnation, reduce the rate of cesarean section and the rate of transvaginal instruments, and reduce the complications of mother and child.

Objective:To investigate the incidence, clinical characteristics and risk factors for hip fractures in patients within two years after stroke onset.Methods:A total of 332 persons with first-onset stroke from the neurology department of our hospital between 1 June 2013 and 31 December 2014 were recruited and were divided into the hip fracture group and the non-hip fracture group.Clinical characteristics were recorded.Vision was tested as normal or impaired.Patients were accessed by the National Institutes of Health Stroke Scale(NIHSS), Behavioral Inattention Test, Baking Tray Task, Mini-Mental State Examination(MMSE), Birgitta Lindmark(BL)motor assessment scale, Berg Balance Scale(BBS), Timed Up & Go(TUG)Scale, and Stops Walking When Talking(SWWT)Scale.The clinic characteristics and risk factors for hip fractures were compared between the two groups after a 2-year follow-up.The accuracy of risk factors for fracture prediction was assessed by the sensitivity, specificity, and positive and negative predictive values.Results:Of 332 patients with stroke, 16 cases fractured their hips within two years after stroke onset, which corresponded to an incidence of 33‰/year(95% CI: 15‰/year-50‰/year). The 2-year mortality rate was 44%(95% CI: 25%-60%)and 48%(95% CI: 42%-54%)in patients with and without hip fractures respectively( χ2=0.036, P=0.724). The mean survival time for patients with and without hip fracture was 2.72 years(95% CI: 1.45-2.79)and 2.21 years(95% CI: 1.48-2.34)respectively.The proportions of patients with previous fractures history( χ2=16.780, P=0.041)and impaired vision( χ2=11.210, P=0.027), MMSE scale score( U=14.220, P=0.031), TUG ≥ 15 s( χ2=18.560, P=0.000)were higher, and SWWT( χ2=20.340, P=0.000)was lower in the hip fracture group than in the non-hip fracture group.The negative predictive values of previous fractures history, impaired vision, TUG and SWWT were higher than their positive predictive value.The specificities of previous fractures history, impaired vision, and SWWT were higher than their sensitivities.And the sensitivity of TUG was higher than its specificity. Conclusions:Hip fractures after stroke are common in elderly patients.Fractures often occur during daytime at home in daily activities.The previous fractures history, visual and cognitive dysfunction and impaired functional mobility are risk factors for hip fractures.We should take measures to prevent falls according to the relevant factors.Among the test scales, the timed up & go(TUG)scale could much more accurately identify patients at high risk for hip fractures.

Objective:To analyze risk factors for acute cerebral infarction(ACI)combined with hyponatremia in patients aged 70 years and older, in order to improve clinical effects of integrated treatment.Methods:From Jan 2017 to Sep 2018, 324 ACI patients aged 70 years and older admitted to the neurology department of our hospital were enrolled.According to serum sodium levels, patients were divided into the normal serum sodium group(NG, n=284)and the hyponatremia group(HG, n=40). Patients in the HG group were further divided into the mild-to-moderate hyponatremia subgroup and the severe hyponatremia subgroup.Multivariate Logistic regression analysis was used to identify the correlation between risk factors for hyponatremia and prognosis.After one month of treatment, prognosis was assessed by using the Neurological Deficit Score(NDS).Results:There were significant differences between the NG and HG groups in age, the National Institutes of Health Stroke Scale(NIHSS)score, drinking, living alone, long-term bed rest, serum levels of C-reactive protein(CRP), D-dimer, fibrinogen(FIB), total cholesterol(CHOL), triglycerides(TG), high density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C), total protein(TP), albumin(ALB), uric acid(UA), apolipoprotein A-1(Apo-A1), potassium, calcium, and phosphorus( P<0.05). Multivariable Logistic regression analysis showed that age( OR=0.917, 95% CI: 0.874-0.962, P=0.000), NHISS score on admission( OR=0.869, 95% CI: 0.783-0.964, P=0.008), drinking( OR=8.001, 95% CI: 3.864-16.567, P=0.000), living alone( OR=0.352, 95% CI: 0.204-0.608, P=0.000), serum CRP( OR=0.975, 95% CI: 0.960-0.990, P=0.001), D-dimer( OR=0.007, 95% CI: 0.001-0.053, P=0.000), CHOL( OR=1.268, 95% CI: 1.058-1.521, P=0.010)and LDL-C( OR=0.357, 95% CI: 0.230-0.552, P=0.000)were independent risk factors, and UA( OR=1.017, 95% CI: 1.013-1.021, P=0.000)was an independent protective factor for ACI combined with hyponatremia in patients aged 70 years and older.Patients in the NG group had better therapeutic effects and prognosis than those in the HG group( P<0.01). Conclusions:Elderly ACI patients aged 70 years and older are prone to hyponatremia.For better clinical effects of integrated treatment, electrolytes should be regularly monitored in elderly patients with related risk factors.

Recent studies heve demonstrated that Akkermansia muciniphila (A.muciniphila) plays an important role in human health and disease , including regulating the development of the immune system and the metabolic phenotype of the host.This article reviews the research progress on A.muciniphila in recent years, focusing on the basic characteristics , the influencing factors of colonization , and the underlying mechanism of maintaining intestinal homeostasis of A.muciniphila.Additionally, the article summarizes the potential association between A.muciniphila and the chronic metabolic diseases such as obesity , atherosclerosis,diabetes mellitus and infectious diseases.The perspect of A.muciniphila as a new generation of probiotics in clinical medicine and the challenge for its industrialization are also discussed in the article .

Objective: To prepare monoclonal antibodies against pneumonia serotype 33F polysaccharides (Pn33Fps) and hepatitis B virus (HBV) surface proteins (HBs) by using the conjugate of Pn33Fps and HBs as antigen. Methods: The conjugate of Pn33Fps and HBs was used as antigen to immunize mice with different immune doses, different immune procedures and different immune sites. Mouse spleen cells with higher antibody level after immunization were isolated and fused with SP2/0 myeloma cells. The hybridoma cells were screened specifically with Pn33Fps or HBs to prepare corresponding monoclonal antibodies. Results: Serum antibodies against Pn33Fps and HBs were induced by immunizing mice with the conjugate. Monoclonal cell lines capable of continuously expressing antibodies against Pn33Fps or HBs were obtained. It has been proved that the recovery rates of samples of Pn33Fps and HBs prepared in three batches tested with ascites monoclonal antibodies prepared by these two monoclonal cell lines were between 95% and 105%. Conclusions Monoclonal antibodies against Pn33Fps and HBs could be prepared simultaneously by immunizing mice with the conjugate of Pn33Fps and HBs and used for the quantitative detection of Pn33Fps and HBs.

Both immunosuppressants and antibiotics (ABX) are indispensable for transplant patients. However, the former increases the risk of new-onset diabetes, whereas the latter impacts intestinal microbiota (IM). It is still unclear whether and how the interaction between immunosuppressants and ABX alters the IM and thus leads to glucose metabolism disorders. This study examined the alterations of glucose and lipid metabolism and IM in mice exposed to tacrolimus (TAC) with or without ABX. We found that ABX further aggravated TAC-induced glucose tolerance and increased insulin secretion. Combined treatment resulted in exacerbated lipid accumulation in the liver. TAC-altered microbial community was further amplified by ABX administration, as characterized by reductions in phylum Firmicutes, family Lachnospiraceae, and genus Coprococcus. Analyses based on the metagenomic profiles revealed that ABX augmented the effect of TAC on microbial metabolic function mostly related to lipid metabolism. The altered components of gut microbiome and predicted microbial functional profiles showed significant correlation with hepatic lipid accumulation and glucose disorders. In conclusion, ABX aggravated the effect of TAC on the microbiome and its metabolic capacities, which might contribute to hepatic lipid accumulation and glucose disorders. These findings suggest that the ABX-altered microbiome can amplify the diabetogenic effect of TAC and could be a novel therapeutic target for patients.

Objective To investigate the application of modified negative pressure closure drainage in early stage of snakebite .Methods 60 patients with early bite ulcer were selected as study objects ,and they were randomly divided into two groups according to the digital table .30 patients in the observation group received vacuum sealing drainage(VSD) combined with chymotrypsin continuous rinsing treatment .30 patients in the control group were given conventional dressing bandaging treatment .The two stage skin grafting time,wound healing time,complications,disa-bility rate,hospitalization time and C reactive protein ( CRP) levels of the two groups were observed .And the treatment effect was analyzed .Results The incidence rates of complications and disability in the observation group were 0.00％and 3.33％,respectively,which were significantly lower than 16.67％and 26.67％in the control group ,and the differences between the two groups were statistically significant (χ2 =4.356,6.405,all P<0.05).The CRP levels of 3 d and 7 d in the observation group were (15.8 ±1.7)mg/L,(6.9 ±1.6)mg/L,respectively,which in the control group were (18.6 ±2.3) mg/L,(13.8 ±1.9) mg/L,respectively,there were statistically significant differences between two groups(t=5.362,15.214,all P<0.01).The two stage skin grafting,wound healing,hospital stay of the observation group were (9.5 ±1.8) d,(24 ±1.8) d,(25.3 ±1.9) d,respectively,which were significantly shorter than those of the control group [(16.2 ±2.6)d,(32.0 ±3.2)d,(33.2 ±3.7)d],the differences were statistically significant(t=11.604,11.93410.403,all P<0.01).Conclusion For patients with injury of cobra bite to early ulcer,using VSD technology combined with chymotrypsin continuous irrigation ,can significantly reduce the level of CRP and the occurrence of complications and disability rate ,shorten the time of two stage skin grafting ,wound healing time,hospitalization time,reduce the pain of patients,it is the best treatment to accelerate recovery .

Objective To examine the incidence ,clinical characteristics ,and risk factors for falls within two years after stroke in elderly patients. Methods A total of 365 elderly stroke patients from the Department of Neurology at the 8th Nanning People's Hospital were recruited from June 1 , 2013 to December 31 ,2014. They were divided into a fall group and a non-fall group and were followed up for two years. The incidence and clinic characteristics of falls were analyzed. The risk factors for falls were analyzed by multiple Logistic regression analysis. Results Of the 365 stroke patients included in this study ,falls were observed in 146(40.2％ )patients. The interval between the stroke and the first fall :72(49.3％ )patients had the first fall within 3 months;22(15.1％ )occurred between 4 and 6 months;20 (13.7％ )between 7 and 12 months ;17 (11.6％ )between 13 and 18 months ;and 15 (10.3％ )between 19 and 24 months.A hundred and five(71.9％ )patients fell during daytime and 41 (28.1％ )patients during night.Eighteen(12.3％ )patients had one fall ;65(44.5％ )patients fell 2 to 4 times ;60(41.1％ )patients fell 5 to 10 times ;and 3(2.1％ )patients fell over 10 times.A total of 709 falls were observed.Places of falls :102(69.9％ )falls happened indoors and 44(30.1％ )falls occurred outdoors.Circumstances of falls :27 (18.5％ )patients fell when turning over ;23 (15.8％ )fell when rising from a seating position ;4(2.7％ )patients fell when showering ;15(10.3％ )patients fell while standing ;9(6.8％ )fell when turning around ;56(38.3％ )fell while walking ;and 12(8.2％ )fell while climbing the stairs or running.The severity of falls :52(35.6％ )patients had no injury ;78(53.2％ ) suffered soft tissue injury ;16 (11.0％ )had fractures ;and 78 (53.2％ )had fear of falling.Multiple Logistic regression analysis showed that age(OR=2.41 ;95％ CI :1.69-3.05) ,history of falls(OR =2.85 ;95％ CI :1.46-3.81) ,history of stroke(OR=1.87 ;95％ CI :1.12-2.79) ,right hemiplegia(OR=2.37 ;95％ CI :1.62-4.59) ,left hemiplegia(OR= 2.47 ;95％ CI :1.46-4.78) ,paraplegia(OR= 2.55 ;95％ CI :1.57-4.98) ,visual impairment(OR=2.35 ;95％ CI :1.35-6.62) ,apraxia(OR=2.53 ;95％ CI :1.42-5.63) ,unilateral spatial neglect (OR=3.34 ;95％ CI :2.82-6.34) ,use of psychotropic medications (OR= 1.76 ;95％ CI :1.11-1.98) ,impaired physical mobility (OR = 1.58 ;95％ CI :1.82-2.91) ,low MMSE scale(OR = 3.42 ;95％ CI :1.38-7.41) ,low Barthel Index score(OR = 2.83 ;95％ CI :0.97-4.68) ,BBS scale<45(OR=2.48 ;95％ CI :1.27-4.18) ,TUG>15seconds(OR=3.56 ;95％ CI :1.91-5.23) ,and lack of rehabilitation therapy (OR=3.42 ;95％ CI :1.38-7.41)were independent predictors for falls(all P<0.05). Conclusions Falls are common among elderly patients within two years after stroke.Most falls happen indoors ,during daytime and while moving.Age ,history of falls ,history of stroke ,hemiplegia ,visual impairment ,apraxia ,unilateral spatial neglect ,use of psychotropic medications ,walk with a walker ,low MMSE scale ,low Barthel Index score ,BBS scale<45 ,TUG>15 seconds ,and lack of rehabilitation therapy are independent risk factors for falls after stroke.

Objective To provide data evidence for early diagnosis of bone and joint damage derived from brucellosis by analyzing its clinical and imaging characteristics.Methods Patients with brucellosis accepted in Ji'nan Infectious Disease Hospital form December 2013 to December 2014 were selected.Patients with bone and joint damage confirmed through imaging were further studied,their epidemiological and clinical characters,CT and MRI characteristics,treatment and outcome were summarized.Results Total of 97.8％ (45/46) patients had a clear contact history,most of them worked in poultry farming,taking up to 67.4％ (31/46).July to October was its peak time for attacking,taking up to 58.7％ (27/46).The clinical manifestations of patients were joint pain,swelling and activities obstacles.In the CT images,there was obvious bony destruction,characterized by multiple round or large areas of low density insect damage sample spots.There was osteosclerotic bone lesions or osteophyte formatted in edge.The paravertebral soft tissue was swelling,and the vertebral body deformation was not obvious,and there was vertebra small joint damage occasionally.In the MRI images,there was vertebral ligaments damage,or soft tissue damage,or osteoproliferation at the edge of the vertebral bodies.There was abnormal signal T1W1 or T2W1 signal,and FS-T1W1 showed high signal,while FS-T2W1 showed slightly high signal.The diagnosis rate of CT,MRI and CT combined MRI for bone and joint damage derived from brucellosis was 76.1％ (35/46),84.8％ (39/46) and 91.3％ (42/46),respectively.The main therapeutic drugs were doxycycline and rifampicin,and the clinical effective rate was 91.3％ (42/46).Conclusion The epidemiological characters,CT and MRI characteristics of bone and joint damage derived from brucellosis have certain representativeness,and the comprehensive investigation is beneficial for clinical diagnosis.