Protein Kinase CK2 Modulates the Calcium Sensitivity of Type 3 Small-conductance Calcium-activated Potassium Channels in Colonic Platelet-derived Growth Factor Receptor Alpha-positive Cells From Streptozotocin-induced Diabetic Mice

Background/Aims@#The gastrointestinal symptom of diabetes mellitus, chronic constipation, seriously affects patients’ life. Whereas, the mechanism of chronic constipation is still ambiguous, resulting in a lack of effective therapies for this symptom. As a part of the smooth muscle cells, interstitial cells of Cajal, and platelet-derived growth factor receptor alpha-positive (PDGFRα+ ) cells syncytium (SIP syncytium), PDGFRα+ cells play an important role in regulating colonic motility. According to our previous study, in PDGFRα+cells in colons of diabetic mice, the function of the P2Y1 purinergic receptor/type 3 small-conductance calcium-activated potassium (SK3) channel signaling pathway is strengthened, which may lead to colonic dysmotility. The purpose of this study is to investigate the changes in SK3 channel properties of PDGFRα+ cells in diabetic mice. @*Methods@#Whole-cell patch clamp, Western blotting, superoxide dismutase activity measurement, and malondialdehyde measurement were main methods in the present study. @*Results@#The present study revealed that when dialysed with low calcium ion (Ca 2+ ) solution, the SK3 current density was significantly decreased in PDGFRα+ cells from diabetic mice. However, the SK3 current density in PDGFRα+ cells was enhanced from diabetic mice when dialysed with high Ca 2+ solution. Moreover, hydrogen peroxide-treatment mimicked this phenomenon in SK3 transgenic HEK293 cells. The subunit of SK3 channels, protein kinase CK2, was up-regulated in colonic muscle layers and hydrogen peroxidetreated HEK293 cells. Additionally, protein phosphatase 2A, the subunit of SK3 channels, was not changed in streptozotocin-treated mouse colons or hydrogen peroxide-treated HEK293 cells. @*Conclusion@#The diabetic oxidative stress-induced upregulation of CK2 contributed to modulating SK3 channel sensitivity to Ca 2+ in colonic PDGFRα+ cells, which may result in colonic dysmotility in diabetic mice.

Analysis of the pathogenesis and risk factors of gallstone / 中华外科杂志

Objective: To explore the pathogenesis and risk factors of gallstone formation. Methods: The findings of hepatobiliary ultrasound and related data were collected from healthy subjects who underwent a physical examination at Xuanwu Hospital of Capital Medical University from January 2012 to December 2021. A total of 98 344 healthy subjects were included in the study,including 48 241 males and 50 103 females,with a ratio of 1∶1.03,aged (42.0±15.6)years(range:14 to 97 years). The gender,age,body mass index,waist circumference,systolic pressure,diastolic pressure,ALT,AST,total bilirubin,fasting blood glucose,triglyceride,total cholesterol,low-density lipoprotein,high-density lipoprotein were collected.Healthy subjects were required to sit for at least 10 minutes before blood pressure was measured.Rresults of fasting venous blood were collected after 8 to 12 hours on an empty stomach.According to the presence of gallstones by ultrasound results, healthy subjects were divided into study group and control group. Data were analyzed by rank-sum tests and χ2 test, and risk factors for gallstone formation were explored by Logistic regression analysis. Results: The incidence of gallstones in this group was 5.42%(5 333/98 344). Among them,the incidence of gallstones in people aged 60 years and above was significantly higher than that in people under 60 years old(15.31%(2 348/15 334) vs. 3.60%(2 985/83 010), χ2=3 473.46,P<0.05).The healthy subjects were divided by age for every 10 years,and the results showed that the incidence of gallstones increased with age. The incidence of gallstones in females was 5.68%(2 844/50 103),greater than 5.16%(2 489/48 241) in males(χ2=11.81,P<0.05). Among them,1 478 cases underwent gallbladder surgical resection due to gallstones,and the operation rate was 27.71%. The operation rate reached the peak between 60 and <70 years old,and decreased after 70 years old. The results of the multivariate analysis showed that,female(OR=1.38, P<0.01),age(OR=1.58, P<0.01),body mass index≥24 kg/m2(OR=1.31, P<0.01),waist circumference≥85 cm(OR=1.24, P<0.01),fasting blood glucose>6.1 mmol/L(OR=1.18,P<0.01),total cholesterol≥5.18 mmol/L(OR=0.87, P=0.019),low-density lipoprotein≥3.37 mmol/L(OR=1.15,P=0.001) were the risk factors for gallstone formation;high-density lipoprotein≥1.55 mmol/L(OR=0.87, P<0.01) was a protective factor for gallstone formation. Conclusions: The incidence of gallstones increases with age in male and female. Gender,age,body mass index,waist circumferenc,fasting blood glucose,total cholesterol,LDL,and HDL are related factors with gallstone formation.

Clinical Study on the Relationship between Gene Mutation Profile and Prognosis in Pediatric Acute Lymphocyte Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the gene mutation profile in children with acute lymphocyte leukemia (ALL) and to explore its prognostic significance.@*METHODS@#Clinical data of 249 primary pediatric ALL patients diagnosed and treated in the Department of Hematological Oncology of Wuhan Children's Hospital from January 2018 to December 2021 were analyzed retrospectively. Next-generation sequencing (NGS) was used to obtain gene mutation data and analyze the correlation between it and the prognosis of children with ALL.@*RESULTS@#227 (91.2%) were B-ALL, 22 (8.8%) were T-ALL among the 249 cases, and 178 (71.5%) were found to have gene mutations, of which 85 (34.1%) had ≥3 gene mutations. NRAS(23.7%), KRAS (22.9%),FLT3(11.2%), PTPN11(8.8%), CREBBP (7.2%), NOTCH1(6.4%) were the most frequently mutated genes, the mutations of KRAS, FLT3, PTPN11, CREBBP were mainly found in B-ALL, the mutations of NOTCH1 and FBXW7 were mainly found in T-ALL. The gene mutation incidence of T-ALL was significantly higher than that of B-ALL (χ2= 5.573，P＜0.05) and were more likely to have co-mutations (P＜0.05). The predicted 4-year EFS rate (47.9% vs 88.5%, P＜0.001) and OS rate (53.8% vs 94.1%, P＜0.001) in children with tp53 mutations were significantly lower than those of patients without tp53 mutations. Patients with NOTCH1 mutations had higher initial white blood cell count （128.64×109/L vs 8.23×109/L，P＜0.001）, and children with NOTCH1 mutations had a lower 4-year EFS rate than those of without mutations (71.5% vs 87.2%, P＝0.037).@*CONCLUSION@#Genetic mutations are prevalent in childhood ALL and mutations in tp53 and NOTCH1 are strong predictors of adverse outcomes in childhood ALL, with NGS contributing to the discovery of genetic mutations and timely adjustment of treatment regimens.

Clinical and genetic analysis of an infant with permanent neonatal diabetes mellitus due to novel variant of insulin gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for an infant with permanent neonatal diabetes mellitus (PNDM).@*METHODS@#Clinical data of the child was collected. Targeted capture-next generation sequencing was carried out to identify the potential variants. Candidate variant was verified by Sanger sequencing of her family members.@*RESULTS@#The child was a 4-month-and-26-day female featuring onset of ketoacidosis accompanied with fasting blood glucose of 24.4 mmol/L, positive urine glucose, decreased serum C-peptide, HbA1c of 9.58%, and negative diabetes autoantibody. Genetic testing revealed that she has carried a heterozygous c.314T>G (p.L105R) variant of the INS gene. Sanger sequencing verified that neither of her parents has carried the same variant, which was also unreported in the literature. The variant was classified as likely pathogenic based on the ACMG guidelines.@*CONCLUSION@#The c.314T>G (P.L105R) variant of the INS gene probably underlay the genetic etiology in this child. Genetic testing should be conducted for children with suspected PNDM for early diagnosis and appropriate treatment.

The Relationship between Occurrence of aGVHD in Patients with Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation and Immune Cell Components in Graft / 中国实验血液学杂志

OBJECTIVE@#To explore the relationship between occurrence of acute graft-versus-host disease (aGVHD) and various immune cell composition in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#The clinical data of 104 patients with AML undergoing allo-HSCT in our hospital were retrospectively analyzed, and the hematopoietic reconstitution and occurrence of GVHD were analyzed. Flow cytometry was used to detect the proportion of various types of immune cells in the grafts, the number of graft composition in patients with different degrees of aGVHD was calculated and compared, and to analyze the correlation between the severity of aGVHD in AML patients after allo-HSCT and the immune cell components in the graft.@*RESULTS@#There was no significant difference in the time of hematopoietic reconstitution between the high number group of total number of nucleated cells (TNC) and the low number group, while the time of neutrophil and platelet reconstruction in the high number of CD34 group was significantly faster than that in the low number of CD34 group (P＜0.05), and the total hospital stay also tends to be shorten. Compared with patients in 0-Ι aGVHD group, both HLA-matched and HLA-haploidentical transplantation, the infusion amounts of CD3+ cells, CD3+CD4+ cells, CD3+CD8+ cells, NK cells and CD14+ monocytes were higher in patients of Ⅱ-Ⅳ aGVHD group， but the difference was not statistically significant (P>0.05); In addition, in patients with HLA-haploidentical transplantation, the number of CD4+CD25+ cells in Ⅱ-Ⅳ aGVHD group was significantly lower than that in 0-Ι aGVHD group (P<0.05), and the same trend was also observed in HLA-matched transplanted patients, but the difference was not significant (P=0.078).@*CONCLUSION@#High number of CD34+ cells in the graft is beneficial to hematopoietic reconstitution in AML patients. To a certain degree, high number of CD3+ cells, CD3+CD4+ cells, CD3+CD8+ cells, NK cells and CD14+ cells tend to increase the occurrence of aGVHD, but high number of CD4+CD25+ regulatory T cells is beneficial to reduce the incidence of aGVHD in AML patients.

GKK1032B from endophytic Penicillium citrinum induces the apoptosis of human osteosarcoma MG63 cells through caspase pathway activation / 中国天然药物

Chemical investigation of the culture extract of an endophytic Penicillium citrinum from Dendrobium officinale, afforded nine citrinin derivatives (1-9) and one peptide-polyketide hybrid GKK1032B (10). The structures of these compounds were determined by spectroscopic methods. The absolute configurations of 1 and 2 were determined for the first time by calculation of electronic circular dichroism (ECD) data. Among them, GKK1032B (10) showed significant cytotoxicity against human osteosarcoma cell line MG63 with an IC50 value of 3.49 μmol·L-1, and a primary mechanistic study revealed that it induced the apoptosis of MG63 cellsvia caspase pathway activation.

Clinical study on tube moxibustion plus point-toward-point needling method in treating refractory facial paralysis / 针灸推拿医学（英文版）

Objective: To evaluate the clinical efficacy of tube moxibustion plus point-toward-point needling method for refractory facial paralysis. Methods: A total of 100 patients with refractory facial paralysis who met the inclusion criteria were randomized into an observation group and a control group, with 50 cases in each group. Both groups were treated with acupuncture by point-toward-point needling method, mainly in the affected eye, cheek and mouth areas. The observation group was given additional tube moxibustion after receiving the point-toward-point needling method, which inserted a tube moxibustion device into the external acoustic meatus 1 cm on the affected side for 20 min. Both groups were treated once a day, 6 times a week, for 4 consecutive weeks. The House-Brackmann scale was scored before and after treatment, and the facial nerve electromyogram data were collected. Results: The total effective rate of the observation group was 93.6％, which was higher than 64.6％ of the control group, and the difference between the two groups was statistically significant (P<0.05). The proportion of new-onset facial paralysis complications (facial synkinesis, facial spasm, facial paralysis perversion, and crocodile tears) in the observation group was 6.4％, which was lower than 35.4％ in the control group. The difference between the two groups was statistically significant (P<0.05). In the observation group, the numbers of cases after treatment with the ratio of action potential amplitude between the affected side and the healthy side increased by 10％-30％ and over 30％ were more than those in the control group. And the difference between the two groups was statistically significant (P<0.05). Conclusion: Tube moxibustion plus point-toward-point needling method has a better effect in improving symptoms of refractory facial paralysis, decreasing the incidence of sequelae, and increasing clinical efficacy than the point-toward- point needling method alone.

Clinical Effect of Jianpi Yangyin Guse Decoction on Podocin and Nephrin and Its Protection Against Podocyte Injury in Diabetic Nephropathy Patients with Qi and Yin Deficiency / 中国实验方剂学杂志

ObjectiveTo observe the clinical effect of Jianpi Yangyin Guse decoction on patients with diabetic nephropathy （DN），and to explore its protection against podocyte injury. MethodThe enrolled 120 DN patients at stages Ⅲ and Ⅳ and diagnosed with Qi and Yin deficiency from January 2017 to January 2020 were randomly divided into observation group and control group. During the same period，20 healthy volunteers were recruited as the normal group. In addition to the basic treatment in control group，patients in the observation group were given Jianpi Yangyin Guse decoction，and the course of treatment lasted for 3 months. The traditional Chinese medicine （TCM）syndrome score，24 h urine protein （24 h UP），urine albumin-to-creatinine ratio（UACR），liver and renal functions，D-dimer， hemoglobin A1c （HbA1c）， urine podocin and nephrin and α-smooth muscle actin （α-SMA） excretion of the two groups were observed before and after treatment，and the changes were statistically analyzed and compared with those in the normal group. ResultAfter treatment，the reduction of TCM syndrome score in the observation group was more significant than that in the control group（P<0.01）. The 24 h UP level，UACR and renal function in the observation group in the 2nd and 3rd months after treatment were lower than the conditions before treatment（P<0.05）， and those in the 3rd month after treatment were decreased compared with the conditions in the control group during the same period. The levels of podocin and nephrin in each month and the α-SMA excretion in the 3rd month after treatment in the observation group were down-regulated compared with the conditions before treatment and in the control group （P<0.05）， and the observation group had reduced α-SMA excretion in the 2nd month after treatment compared with before treatment. There were no marked changes in D-dimer and liver function of the two groups before and after treatment. The level of HbA1c in the observation group was higher than that in the control group after treatment（P<0.05）. ConclusionJianpi Yangyin Guse decoction has desirable clinical efficacy in DN patients，and its mechanism may be related to reducing podocin and nephrin and α-SMA excretion levels.

Magnetic stimulation in the treatment of urinary retention after spinal cord injury / 中华物理医学与康复杂志

Objective:To observe any effect of magnetic stimulation of the primary motor cortex and sacral nerve roots on urinary retention after spinal cord injury.Methods:Forty patients experiencing urine retention after a spinal cord injury were randomly divided into an experimental group and a control group, each of 20. Both groups received conventional treatment and repeated magnetic stimulation of the roots of the sacral nerve. The experimental group also received repeated magnetic stimulation of the bilateral primary motor cortices (M1 region). Bladder capacity and pressure indices, residual urine volume and life quality were evaluated in both groups before and after 8 weeks of treatment.Results:After the treatment, the average maximum bladder pressure, first sensation capacity, residual urine volume and life quality score of both groups had improved significantly, but the improvements in average first sensation capacity, residual urine volume and life quality score of the experimental group were significantly greater than those of the control group. There was, however, no significant difference in the groups′ average maximum bladder pressure after the treatment.Conclusion:Magnetic stimulation of the primary motor cortex and sacral nerve roots can significantly improve the sensory function of the bladder, reduce residual urine volume and improve the life quality of persons experiencing urinary retention after a spinal cord injury.

Guidelines investigation and technical considerations of virus safety during investigational new drug application of innovative monoclonal antibody products / 药学学报

With the development of antibody manufacturing technology and improvement of new drug research in domestic industry, more innovative monoclonal antibody products submitted investigational new drug (IND) application. At the same time, monoclonal antibody products from abroad which have been approved marketing authorization and/or conducted clinical trials submitted IND applications in China. The National Medical Products Administration (NMPA) issued the "Guideline of Investigational New Drug Application" (No. 16, 2018) which emphasized the chemical, manufacturing, and control (CMC) regulatory, and dossier requirements in IND application, greatly promoted the application quality of innovative biological products. However, compared to the Food and Drug Administration (FDA) and European Medicines Agency (EMA), our particular guidelines are insufficient, such as guideline on virus safety evaluation of biotechnological investigational medicinal products. This review investigated the questions raised by sponsors from 2018 to 2020, including the end of production cell (EOPC) and/or unprocessed bulk (UPB) testing and virus removal or inactivation validation. Meanwhile, sponsors submitted different dossiers due to differences in understanding of stage requirements of guidelines from domestic and abroad. Based on the guidelines of virus safety from NMPA, FDA, and EMA, and the technical considerations, this review puts forward personal suggestions on the adventitious agents testing and virus removal or inactivation validation in manufacturing process, aim to ensure virus safety of innovative monoclonal antibody products in clinical trials.

How Cerebral Vessel Tortuosity Affects Development and Recurrence of Aneurysm: Outer Curvature versus Bifurcation Type / 대한뇌졸중학회지

Background@#and Purpose Previous studies have assessed the relationship between cerebral vessel tortuosity and intracranial aneurysm (IA) based on two-dimensional brain image analysis. We evaluated the relationship between cerebral vessel tortuosity and IA according to the hemodynamic location using three-dimensional (3D) analysis and studied the effect of tortuosity on the recurrence of treated IA. @*Methods@#We collected clinical and imaging data from patients with IA and disease-free controls. IAs were categorized into outer curvature and bifurcation types. Computerized analysis of the images provided information on the length of the arterial segment and tortuosity of the cerebral arteries in 3D space. @*Results@#Data from 95 patients with IA and 95 controls were analyzed. Regarding parent vessel tortuosity index (TI; P<0.01), average TI (P<0.01), basilar artery (BA; P=0.02), left posterior cerebral artery (P=0.03), both vertebral arteries (VAs; P<0.01), and right internal carotid artery (P<0.01), there was a significant difference only in the outer curvature type compared with the control group. The outer curvature type was analyzed, and the occurrence of an IA was associated with increased TI of the parent vessel, average, BA, right middle cerebral artery, and both VAs in the logistic regression analysis. However, in all aneurysm cases, recanalization of the treated aneurysm was inversely associated with increased TI of the parent vessels. @*Conclusions@#TIs of intracranial arteries are associated with the occurrence of IA, especially in the outer curvature type. IAs with a high TI in the parent vessel showed good outcomes with endovascular treatment.

How Cerebral Vessel Tortuosity Affects Development and Recurrence of Aneurysm: Outer Curvature versus Bifurcation Type / 대한뇌졸중학회지

Background@#and Purpose Previous studies have assessed the relationship between cerebral vessel tortuosity and intracranial aneurysm (IA) based on two-dimensional brain image analysis. We evaluated the relationship between cerebral vessel tortuosity and IA according to the hemodynamic location using three-dimensional (3D) analysis and studied the effect of tortuosity on the recurrence of treated IA. @*Methods@#We collected clinical and imaging data from patients with IA and disease-free controls. IAs were categorized into outer curvature and bifurcation types. Computerized analysis of the images provided information on the length of the arterial segment and tortuosity of the cerebral arteries in 3D space. @*Results@#Data from 95 patients with IA and 95 controls were analyzed. Regarding parent vessel tortuosity index (TI; P<0.01), average TI (P<0.01), basilar artery (BA; P=0.02), left posterior cerebral artery (P=0.03), both vertebral arteries (VAs; P<0.01), and right internal carotid artery (P<0.01), there was a significant difference only in the outer curvature type compared with the control group. The outer curvature type was analyzed, and the occurrence of an IA was associated with increased TI of the parent vessel, average, BA, right middle cerebral artery, and both VAs in the logistic regression analysis. However, in all aneurysm cases, recanalization of the treated aneurysm was inversely associated with increased TI of the parent vessels. @*Conclusions@#TIs of intracranial arteries are associated with the occurrence of IA, especially in the outer curvature type. IAs with a high TI in the parent vessel showed good outcomes with endovascular treatment.

The incidence of complications associated with arm ports and chest ports: a Meta-analysis and systematic review / 中国实用护理杂志

Objective:To compare the incidence of complications associated with arm and chest ports by Meta-analysis.Methods:To Janurary 2019, studies published in PubMed, Embase, CINAHL, Cochrane, CBM and Wanfang regarding complication comparison between arm ports and chest ports were searched. Newcastle-Ottawa Scale was applied to evaluate the quality of studies. Review Manager 5.3 software was applied to conduct this meta-analysis.Results:A total of 19 articles covering 4 203 patients were included. The results showed that the incidence of pneumothorax ( OR value was 0.22, 95% CI0.05-0.88, P value was 0.03) and artery injury ( OR value was 0.24, 95% CI0.07-0.77, P value was 0.02) between arm ports group and chest ports group were statistically significant. No significant difference was observed in infection ( OR value was 0.81, 95% CI0.58-1.12, P value was 0.20), thrombosis ( OR value was 1.25, 95% CI0.64-2.45, P value was 0.52), extravasation ( OR value was 1.13, 95% CI0.54-2.35, P value was 0.75), catheter misplacement ( OR value was 1.58, 95% CI0.95-2.61, P value was 0.08), skin incision ( OR value was 0.64, 95% CI0.23-1.74, P value was 0.38), sepsis ( OR value was 0.68, 95% CI0.27-1.70, P value was 0.41) and exudate ( OR value was 0.88, 95% CI0.32-2.42, P value was 0.80). Conclusion:The incidence of pneumothorax and artery injury in arm ports is significantly lower than in chest ports, there was no difference in other complications. More studies are needed to further confirm the advantages of arm ports.

A prospective study of correlation between serum leptin,resistin and adiponectin levels and preeclampsia / 中国实用妇科与产科杂志

OBJECTIVE: To investigate the relationship between serum leptin,resistin and adiponectin levels and preeclampsia.METHODS: The study was a case-control study.All enrolled pregnant women were selected from January2013 to June 2015 in Peking Union Medical College Hospital,Peking Union Medical College Peking Union Medical College Hospital.In the case group,74 patients were further divided into early-onset and late-onset subgroups(51 cases and 23 cases respectively).The control group enrolled 79 uncomplicated pregnant women who delivered full-term babies during the study period.Three adipokines were measured by enzyme linked immunosorbent assay.RESULTS: Leptin level8.98)μg/L,P<0.001).Positive correlation between leptin level and BMI was observed in normotensive pregnancies(r=0.651,P<0.001),but the correlation disappeared in preeclampsia patients.The serum resistin level in the case group was significantly higher than that in the control group(14.08±6.10)vs.(9.99±8.33)μg/L,P<0.001),and there was no correlation between serum resistin level and BMI.There was no significant difference in adiponectin level between the case group and the control group.CONCLUSION: Serum resistin and leptin in preeclampsia population are significantly higher than those in normotensive pregnancies,and the underlying mechanism of their elevation needs to be further investigated.The correlation between adiponectin and preeclampsia is not clear.

Clinical Significance of CRLF2 High Expression in Bone Marrow Mononuclear Cells from Children with Acute Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To detect the expression of CRLF2 in bone marrow mononuclear cells from children with newly diagnosed acute lymphoblastic leukemia(ALL) and to explore its clinical significance in pediatric ALL.@*METHODS@#A total of 218 children with newly diagnosed ALL who achieveal the complete remission and had the complete follow-up information were selected, and the expression level of CRLF2 in bone marrow mononuclear cells of these children was detected by real-time fluorescent quantitative PCR, and the significance of CRLF2 expression level in clinical prognosis of ALL children was analyzed by using statistical method.@*RESULTS@#28 cases in 218 children with complete data showed high expression of CRLF2. The cumulative recurrence rate in the CRLF2 high expression group was significantly higher than that in the low expression group (53.6% vs 12.6%) (P＜0.01). The predicted 5-year recurrence-free survival rate (RFS) of ALL children with CRLF2 high expression was significantly higher than that of low expression group (P＜0.01). There was no significant difference in the predicted 5-year RFS between ALL children with CRLF2 low and high expression in the standard-risk(SR) group (P＞0.05). The predicted 5-year RFS of ALL children with CRLF2 low expression was higher than that of ALL children with CRLF2 high expression in the intermediate-risk (IR) and high-risk (HR) groups. (P＜0.05). Cox analysis showed that CRLF2 high expression is an independent risk factor for the relapse of children with ALL.@*CONCLUSION@#The recurrence rate of pediatric ALL with CRLF2 high expression is high, and CRLF2 high expression is an important prognostic factor for high risk of relapse in ALL children with IR and HR. It is necessary to use CRLF2 expression as an indicator of risk stratification in pediatric ALL.

The observation on the clinical effect of CSEA by using orbital needle external needle in PCEA post cesarean delivery / 中国医学装备

Objective: To observe the clinical effect of combined spinal epidural anesthesia(CSEA)by using orbital needle in patient-controlled epidural analgesia(PCEA)post cesarean delivery.Methods: 94 puerperas who received cesarean were divided into observation group(47 cases)and control group(47 cases).The patients of two groups were narcotized by using CSEA combined with PCEA.And the observation group adopted a new type of lumbar vertebral combined puncture needle and the control group adopted the traditionally typical lumbar vertebral combined puncture needle.The score of visual analogue scale(VAS)and sedation score of Ramesay of two groups of postoperative 1h,4h,12h,24h and 48h were compared.And the number of times in 48h,the drug dosage and adverse reaction of using analgesia pump also were compared.Results: In postoperative 12 h,the VAS scores of the two groups showed an increasing trend.And the VAS scores of pain of two groups within postoperative 12-48 h decreased gradually.The differences of VAS scores of pain of two groups within postoperative 1-12h and 12-48h between observation group and control group were statistically significant(F=29.596,F=156.366,P＜0.05),respectively.And the VAS scores of pain post operative 4h and 12h of observation group [(2.01±0.51)and(3.49±0.74)]were significantly lower than that of control group [(2.32±0.47)and(3.85±0.69)](t=3.064,t=2.439,P＜0.05),respectively.Within postoperative 1-48h,there were no significant fluctuation in sedation score of Ramesay and the difference of sedation score between the two groups were no significant.And the number of times(11.35±3.04)and drug dosage(65.67± 7.98)mL of using analgesic pump of observation group were significantly lower than that of control group [(20.08±5.32)and(82.07 ± 9.05)mL],(t=9.768,t=9.318,P＜0.05),respectively.Besides,the incidences of postoperative nausea and skin pruritus of observation group(4.26％and 14.89％)were significantly lower than that of control group(17.02％and 34.04％)(x2=4.029,x2=4.663,P＜0.05),respectively.Conclusion: The analgesia effect of orbital needle external needle in implementing CSEA for cesarean delivery is better than that of traditional needle inner needle,and its adverse reactions are less and it is safety.

Discussion on diagnostic value of urinary neutrophil gelatinase-associated lipocalin in the diagnosis of acute pyelonephritis in children / 天津医药

Objective To explore the diagnostic value of urine neutrophil gelatinase-associated lipocalin (NGAL) in children with acute pyelonephritis. Methods A total of 104 children with urinary tract infection admitted to Tianjin Children's Hospital from December 2016 to May 2017 were selected in this study, including 61 cases with acute pyelonephritis (group APN) and 43 with lower urinary tract infection (group non-APN). The serum levels of beta 2-Microglobulin (β2-MG), cystatin C (CysC), C-reactive protein (CRP), procalcitonin (PCT) and urine levels of NGAL were compared between two groups.Receiver operating characteristic(ROC)curves were drawn to evaluate the diagnostic values of serum β2-MG,CysC,CRP,PCT and urine NGAL.Results The serum levels of CRP,PCT,β2-MG and urinary NGAL were significantly higher in APN group than those in non-APN group (P < 0.05). There was no significant difference in serum CysC level between two groups(P>0.05).The areas under the ROC curve(AUC)for serum CRP,PCT,and urinary NGAL were 0.838,0.898 and 0.963.The optimal cutoff value of serum CRP was 22.6 mg/L,the sensitivity was 75.4% and the specificity was 83.7%. The optimal cutoff value of serum PCT was 0.285 μg/L, the sensitivity was 77.0% and the specificity was 93.0%.The optimal cutoff value of urine NGAL was 473 μg/L,the sensitivity was 82.0% and the specificity was 97.7%.Conclusion Urinary NGAL has high diagnostic value for APN in children,and which is helpful for the early identification of APN.

Analysis of SMPD1 gene mutations in Chinese patients with Parkinson's disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the role of sphingomyedlin phosphodiesterase 1 (SMPD1) gene mutations in the pathogenesis of Parkinson's disease (PD).</p><p><b>METHODS</b>For 110 Chinese patients with PD, all exons of the SMPD1 gene were sequenced, and the results were compared with reference sequence from GenBank to identify possible mutations.</p><p><b>RESULTS</b>A novel heterozygous mutation Ex2:c.677C>A/p.P226Q (likely pathogenic) was identified in a patient, which resulted in substitution of Glutamic acid by Proline at position 226. In addition, two known single nucleotide polymorphisms (SNPs) Ex1:c.107T>C/p.V36A (benign) and Ex6:c.1522G>A/p.G508R (benign), and three previously reported SMPD1 mutations Ex2:c.T371T>G/p.L124R (uncertain significance), Ex2:c.636T>C/P.(=)(benign) and Ex6:c.1598C>T/p.P533L (uncertain significance) were identified. The novel p.P226Q mutation and p.P533L mutation were predicted to have a possibly damaging effect on the structure and function of SMPD1 protein, which in turn may lead to PD.</p><p><b>CONCLUSION</b>The mutation rate of the SMPD1 gene was 3.64% among Chinese PD patients. Genetic variants of SMPD1 may increase the risk of PD.</p>

Pembrolizumab for Refractory Metastatic Myxofibrosarcoma: A Case Report / Journal of the Korean Cancer Association, 대한암학회지

Myxofibrosarcoma is a rare tumor, refractory to cytotoxic chemotherapy and radiotherapy. Pembrolizumab is an innovative immunotherapy drug consisting of programmed death receptor ligand 1 antibody proven to be useful for numerous types of cancer cells. A patient had been diagnosed with metastatic myxofibrosarcoma, refractory to radiotherapy and conventional cytotoxic chemotherapy. The patient achieved a partial response during palliative chemotherapy with pembrolizumab for 14 cycles. To the best of our knowledge, this is the first case report demonstrating the efficacy of pembrolizumab for refractory myxofibrosarcoma.

Chemotherapy versus Best Supportive Care in Advanced Biliary Tract Carcinoma: A Multi-institutional Propensity Score Matching Analysis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Although chemotherapy is recommended by various guidelines for advanced biliary tract cancer (BTC), the evidence supporting its use over best supportive care (BSC) is limited. The aim of this study was to investigate the survival benefit of chemotherapy over that of BSC in advanced BTC patients. MATERIALS AND METHODS: Advanced BTC patientswith a good performance status (Eastern CooperativeOncologyGroup [ECOG] 0-2) were eligible for the study. Data were retrospectively collected from four tertiary cancer centers and analyzed using propensity score matching (PSM). Of the 604 patients enrolled, 206 received BSC and 398 received chemotherapy. PSM analysis was performed using the following variables: age, ECOG status, carcinoembryonic antigen (CEA) level, white blood cell level, albumin level, total bilirubin level, and aspartate aminotransferase level. The sample size of each group was 164 patients after PSM. Median survival was compared between the two groups by using the Kaplan-Meier method, and prognostic factors were investigated using Cox proportional regression analysis. RESULTS: In post-PSM analysis, the respective median survival for the chemotherapy and BSC groups was dependent on the following prognostic factors: total population, 12.0 months vs. 7.5 months (p=0.001); locally advanced disease, 16.7 months vs. 13.4 months (p=0.490); cancer antigen 19-9 ≤ 100 IU/mL, 12.7 months vs. 10.6 months (p=0.330); and CEA ≤ 3.4 ng/mL, 17.1 months vs. 10.6 months (p=0.052). CONCLUSION: Chemotherapy improved overall survival of patients with advanced BTC who had a good performance status. However, this survival benefit was not observed in BTC patients with locally advanced disease or with lower tumor marker. Individualized approach is needed for initiation of palliative chemotherapy in advanced BTC.