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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.
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Calciphylaxis is a vascular disease caused by a combination of multiple factors, and the calcified ischemic lesion results in the severe skin damage accompanied by unbearable pain. Calciphylaxis tends to occur in patients with end-stage renal disease, and the treatment of this disease faces enormous challenges. Current treatment recommendations are mainly based on clinical experience and observational research reports, and there is still a lack of clinical practice standards or consensus for managing calciphylaxis. Therefore, this paper will review the effective treatment methods and off-label use of calciphylaxis based on literature reports, providing reference for the clinical treatment of the disease.
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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.
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Objective To investigate the expression level of miRNA-146a (miR-146a) in retinal pigment epithelial (RPE) cells aging and age-related macular degeneration (AMD),and discuss its regulation mechanism of AMD by repressing VEGF-A.Methods The expressions of miR-146 and VEGF-A were examined by qRT-PCR in RPE cells in mice aged 2 months,8 months,12 months,18 months or 24 months,and in RPE cells from 75 years old AMD patients.The protein level of VEGF-A was also detected by Western Blotting.Finally,the effects of overexpression of miR-146a in APRE-19 cell line on expression of VEGF-A was checked.Results MiR-146 was up-regulated to 8 times or 24 times at 18 months or 24 months aged mice,and the expression of VEGFA was down-regulated in aging RPE from 1.5 times to 0.8 times.However,the expression of miR-146 decreased to 14.5 times and VEGF-A increased in RPE cells of AMD.In cultured cells,overexpression of miR-146a inhibited the expression of VEGF-A.Conclusion Up-regulation of miR-146a in aging RPE cells and its down-regulation in AMD suggest a potential of miR-146a as molecular marker.MiR-146a overexpression inhibits the expression of VEGF-A,supporting a potential clinical treatment of miR-146 in AMD.
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Objective To evaluate the effect of electroacupuncture (EA) preconditioning on the activity of dynamin-related protein 1 (Drp1) in brain tissues during cerebral ischemia-reperfusion (I/R) in rats.Methods A total of 126 pathogen-free healthy adult male Wistar rats,weighing 250-300 g,were divided into 3 groups (n =42 each) using a random number table:sham operation group (group S),group I/R and EA preconditioning group (group EA).In group S,the blood vessels were only separated but not occluded.In group I/R,a nylon thread with rounded tip was inserted into the left middle cerebral artery advanced cranially until resistance was met,and middle cerebral artery occlusion was maintained for 2 h followed by reperfusion.In group EA,Baihui acupoints were stimulated with an electric stimulator (2/ 15 Hz disperse-dense waves,intensity 1 mA) for 30 min,lasting for 5 consecutive days,and the model of focal cerebral I/R was established at 24 h after the last stimulation.At 6,24 and 48 h of reperfusion,the neurologic deficit was assessed and scored,the mitochondria in the cerebral cortex on the ischemic side were extracted,the expression of Drpl in mitochondria was detected using Western blot,the mitochondrial uhrastructure was examined with an electron microscope,and neuroapoptosis was measured using TUNEL.The apoptosis rate was calculated.Results Compared with group S,the neurological deficit score and apoptosis rate were significantly increased,and the expression of Drpl in mitochondria was up-regulated at each time point in I/R and EA groups (P＜0.05).Compared with group I/R,the neurological deficit score and apoptosis rate were significantly decreased,and the expression of Drpl in mitochondria was down-regulated at each time point in group EA (P＜0.05).Conclusion The mechanism by which EA preconditioning reduces cerebral I/R injury may be related to inhibiting the activity of Drpl and thus inhibiting the excessive fission of mitochondria in rats.
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Objective To investigate the relationship between C-C chemokinereceptor type 2 (CCR2) and p38 mitogen-activated protein kinase (p38MAPK) signaling pathway in the dorsal root ganglion of rats and further clarify the mechanism of inflammatory pain.Methods Sevemy-two female Sprague-Dawley rats,weighing 150-180 g,aged 3-4 months,were randomly divided into 3 groups (n =24 each) using a random number table:control group (group C),inflammatory pain group (IP group) and CCR2 inhibitor RS102895 group (group RS).Inflammatory pain was induced by subcutaneous injection of Freund's adjuvant 100μl into the plantar surface of the right hindpaw.RS102895 20 mg/kg was injected subcutaneously once a day for 7 consecutive days in addition to Freund's adjuvant in group RS.Mechanical paw withdrawal threshold (MWT) was measured before injection and at 1,3,5 and 7 days after injection.At 3,5 and 7 days after injection,8 rats in each group were sacrificed and the dorsal root ganglions were removed for determination of the expression of CCR2 and phosphor-p38MAPK (p-p38MAPK) (by immuno-histochemical staining),and CCR2 and p38MAPK mRNA (using fluorescent quantitative PCR).Immuno-histochemical staining was scored.Results Compared with group C,MWT was significantly decreased after injection,the number of p-p38MAPK positive neurons and immuno-histochemical staining score were increased,and CCR2 and p38MAPK mRNA expression was up-regulated in IP and RS groups.Compared with group IP,MWT was significantly increased after injection,the number of p-p38MAPK positive neurons and immuno-histochemical staining score were decreased,and CCR2 and p3gMAPK mRNAexpression was down-regulated in RS group.Conclusion CCR2 in the dorsal root ganglion is involved in the development of inflammato pain possibility through activating p38MAPK signaling pathway in rats.
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Objective To study the effects of bone marrow mesenchymal stem cells modified by brain-derived neuro-trophic factor ( BDNF) gene on the repair of spinal cord injury by electrophysiological assay .Methods Thirty healthy Spra-gue-Dawley rats (male and female) were randomly divided into 3 groups:Blank group, 10 rats (removal of the lamina only and exposed spinal dura mater );spinal cord injury (SCI) group,10 rats;and cell transplantation after SCI group , 10 rats. Eight rats of them were selected randomly and detected their SEP and MEP , and evaluated the degree of recovery of motor scores in the rats at 1 d, 7 d, 14 d, 21 d, 30 d, and 60 d.Result Since 4 days after cell transplantation , the process of hind limbs changes was as follows:at the 1-4 days after injury , the injury side hind limb had flaccid paralysis , mopping the floor walk, the movement of contralateral hind limb was gradually recovered from the initial injury , the injury side hind limb had spastic paralysis in 5-9 days after SCI;during 10-14 days, the injury side had a few activities;the contralateral side re-covered to a less normal state;At 15-21 days, activities of the injury side improved obviously , until the 30th day.The activ-ity and muscle tension degree of the injury side recovered most obviously .After 30 days no more obvious improvement was ob-served.Immunohistochemistry showed that the transplanted mesenchymal stem cells , which were induced and labeled firstly , survived at the damage spinal cord , and behavioral observation found that the cell transplantation improved exercise capacity of the rats injured before .Conclusion Bone marrow mesenchymal stem cells modified by BDNF gene can partially promote the recovery of nerve transmission function and nerve regeneration .
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Objective To investigate the efficacy and pregnancy outcomes of women receiving double-catheter epidural block in labor analgesia, and compare the results with single-catheter epidural block.Methods A double-blind clinical trial was conducted on 206 full-term singleton primiparas, aged 25-35 and at the 37 -42 weeks of gestation who delivered at the Department of Obstetrics, Qingdao Municipal Hospital from August 2006 to December 2008, which were randomly divided into two groups:double-catheter epidural block ( group D, n = 103) and single-catheter epidural-block ( group S, n = 103 ).Women in group D were given mixture of 0.1% repivacaine hydrochloride and 0.5 mg/L sufentinil 4 -6 ml as initial dose.Patient control epidural analgesia pump (PCEA) was connected with the upper catheter after 45 minutes.A bolus dose of 4 -6 ml analgesia mixture was infused according to the condition through the lower catheter.Women in group S received analgesia mixture 10 - 15 ml as initial dose and PCEA pump was connected after 45 minutes.Oxytocin was infused in both groups according to uterine contraction after 30 minutes.The following indexes was observed: ( 1 ) visual analogue scales (VAS); (2) modified Bromage Scores;(3) the total dose of analgesia mixture, the percentage of oxytocin infusion, duration of labor and duration of the second stage of labor; (4) fetal birth weight and Apgar scores( 1,5 minutes); (5) mode of delivery; (6) the concentration of plasma cortisol and angiotension Ⅱ at the beginning of regular uterine contraction and at the time when cervical dilated to 4 cm and 10 cm and fetal disengagement; (7)anesthesia-related complications.Results ( 1 )The neonatal birth weight and Apgar scores ( 1,5 minutes)of group D were (3456 ±468)g, 9.8 ±0.6 and 9.9 ±0.7, respectively, while(3399 ±569) g, 9.8 ±0.5 and 9.9 ±0.7 in group S( P ＞0.05).No motor function block was reported in any group and the modified Bromage score was zero.(2) The total dose of analgesia mixture in group D was similar to that in group S [(57 ±9) ml vs.(58 ±11) ml, P＞0.05].However, the percentage of women received oxytocin in group D was smaller [59.2% (61/103) vs.81.6% (84/103), P ＜ 0.01], and the total time of labor and the duration of second stage of labor in group D were shorter[(532 ± 140) minutes vs.(608 ± 150) minutes;(46 ± 31 ) minutes vs.(60 ± 34) minutes, P ＜ 0.05].(3) There were no significant differences in VAS at 30 minutes after initial dose and in the first stage of labor between group D and S ( 1.2 ± 1.1 vs 1.2 ± 1.1,1.1 ± 1.1 vs.1.2 ± 1.0, P＞0.05).VAS at the second stage of labor stage was lower in group D than in group S ( 1.2 ± 1.1 vs.4.5 ± 2.2, P ＜ 0.01 ).(4) The rate of cesarean section, instrumental delivery and episiotomy in group D were lower than in group S (7.8% vs.17.5%, 7.8% vs.15.5%, 10.7% vs.18.4%, P ＜ 0.05).The incidence of fetal distress and meconium-stained amniotic fluid as the indication of cesarean section were similar between the two groups (P ＞ 0.05 ).Lower incidence of fetal malpresentation and arrested second stage of labor were shown in group D than in group S (2.9% vs.9.7%, 1.0% vs.5.8%, P ＜ 0.05 ).(5) The concentration of plasma cortisol and angiotension Ⅱ were lower in group D than in group S [(86 ±25) ng/L vs.( 100 ±20) ng/L, (278 ±53) nmol/L vs.(311 ±53)nmol/L, P＜0.05] only at the end of second stage of labor, but not at any other times(P ＞0.05).(6) No serious anesthesia-related complications were reported in any groups.Some light backache around the puncture point were complained by 29.1% (30/103) of the women in group D and 31.1% (32/103) in group S(P ＞0.05).Conclusion Double-catheter epidural block can provide better analgesia effect during labor than single-catheter epidural block, without any adverse influence on delivery outcomes.