Geritinib in the targeted therapy of acute myeloid leukemia with FLT3 mutation: report of 5 cases and review of literature / 白血病·淋巴瘤

Objective:To investigate the efficacy and safety of geritinib in the treatment of acute myeloid leukemia (AML) with FLT3 mutation.Methods:The clinical data of 5 AML patients with FLT3 mutation who were diagnosed in the University of Hong Kong-Shenzhen Hospital, Shenzhen People's Hospital, Shenzhen Second People's Hospital, Shenzhen University General Hospital from March 2020 to April 2021 were retrospectively analyzed. Relapsed patients concurrently received two- or three-drug chemotherapy combined with geritinib. Blood routine was checked once a week; liver function and renal function were checked once every 2 weeks during treatment. Bone marrow puncture was performed once every 1 to 3 months to monitor the bone marrow morphology, minimal residual disease (MRD) and FLT3 mutation expression levels. The efficacy, side effects, overall survival of these patients were analyzed after treatment with geritinib.Results:The white blood cell was increased in all the 5 patients at the initial diagnosis. FLT3 mutations analysis showed FLT3-internal tandem duplication (ITD) (3 cases) and FLT-3 tyrosine-kinase domain (TKD) (2 cases). Among 5 patients, 1 patient was relapse-free with maintenance therapy of oral geritinib after hematological stem cell transplantation (HSCT) for 60 days; among other 4 relapsed and refractory patients, 1 female patient after pregnancy relapsed after transplantation and then achieved complete remission followed by the maintenance therapy with geritinib after oral geritinib, 1 16-year-old patient achieved treatment outcome close to the complete remission after treatment with geritinib, 1 patient achieved complete remission after treatment with geritinib, and then underwent haplo-HSCT followed by the maintenance therapy with geritinib and the other 1 relapsed patient achieved complete remission after treatment with geritinib. After transplantation, 3 patients receiving maintenance treatment of geritinib did not relapse. The main side effects included anemia, decreased neutrophil count, rash, and increased aminotransferase. The median follow-up time of 5 patients was 15 months (6-20 months). All 5 cases survived until the last follow-up in November 2021 and 4 patients were disease-free.Conclusions:Relapsed and refractory AML patients with FLT3 mutation can achieve complete remission after treatment with geritinib and get a chance for transplantation. Geritinib may reduce the risk of recurrence after transplantation and improve survival rate. No serious side effects occur in geritinib treatment.

Research advancement on the complications of neuroscopy surgery / 中国医师杂志

With the progress of imaging, optics and other science and technology, neuroendoscopy technology has been greatly developed, the application of more and more widely, but also become one of the techniques that neurosurgeons must be familiar with and master. With the further popularization of neuroendoscopy technology, related complications have also attracted wide attention. Endoscopic techniques are being used extensively used in the current times for the diagnosis and treatment of numerous intracranial pathologies. Although the incidence of complications related to neuroendoscopy is lower than that of traditional surgery, neuroendoscopy itself may bring complications such as hemorrhage, cerebrospinal fluid leakage, subdural hematoma and so on. This article reviews the complications related to neuroendoscopic surgery, in order to improve the understanding of complications and timely and correct treatment, so as to improve the curative effect of neuroendoscopic surgery.

Correlation between genotype and pathogen in chronic granulomatous disease / 中华实用儿科临床杂志

Objective:To summarize the clinical characteristics, common images, pathogens, and gene mutation types of chronic granulomatosis disease (CGD) in 19 children.Methods:The clinical manifestations, laboratory findings, treatment, and prognosis of 19 patients diagnosed with CGD in Hong Kong University-Shenzhen Hospital from December 2012 to December 2018 were analyzed.Results:The 19 patients were all males and confirmed as CGD by the dihydrorhodamine test and gene sequencing.The age of the first infection was mostly 1 month after birth(13 cases), and the age of clinical diagnosis ranged from 2 months to 10 years.Sixteen mothers were carriers.The patients presented with pulmonary fungal infection (19/19 cases), Bacillus Calmette Guerin (BCG)-osis (14/19 cases), lymphadenitis (14/19 cases), perianal abscess (9/19 cases), skin abscess (5/19 cases) and ulcerative colitis (2/19 cases). There were 59 positive cultures.Pathogens included fungi (9 cases), Klebsiella pneumonia (8 cases), mycobacteria (7 cases), Streptococcus Viridans (5 cases), Escherichia coli (3 cases), gram-positive bacteria (3 cases), Staphylococcus aureus (3 cases), and Burkholderia cenocepacia (2 cases). Gene mutations were found in all 19 patients, including 17 cases of CYBB, 1 case of CYBA and 1 case of NCF2.The type of mutations included nonsense mutations (6 cases), deletion mutations (5 cases, including 2 large fragment deletions), splice mutations (3 cases) and missense mutations (5 cases). Five mutations were novel.Splice mutations in 3 cases often led to skin abscess, perianal abscess and lymphadenitis.Two patients with large deletion mutations had more serious infection than other patients. Conclusions:In China, CGD is characterized with pulmonary infection and disseminated BCG-osis.Mycobacteria are common pathogens of CGD, and fungi are dominant pathogens of CGD.The most common infection is respiratory infection. Klebsiella pneumonia and Escherichia coli often lead to perianal abscess.The relationship between gene mutation types and clinical phenotypes requires further verification by big data.

Relationship between abnormal monitoring of VEEG and prognosis in patients with refractory epilepsy / 实用医学杂志

Objective To investigate and study the relationship between abnormal monitoring and prognosis of long range video electroencephalogram(VEEG)in patients with intractable epilepsy. Methods 100 patients from March 2012 to May 2017 in our hospital whose diagnosis and treatment of refractory epilepsy were the research object,all patients were given VEEG monitoring records,epilepsy typing characteristics and antiepileptic drug(AEDs)use survey,prognosis of all patients and the correlation analysis. In 100 cases,GTCS 60 cases,CPS 30 cases,CPS-GTCS 10 cases;56 cases treated with sodium valproate,lamotrigine treatment in 44 cases. Results VEEG monitored 80 cases of epileptiform discharge in 100 patients and 20 cases without epileptiform discharge. There was no significant difference in the incidence of epileptiform discharges between different epileptic patients in VEEG monitoring(P > 0.05),and there was no significant difference in the incidence of epileptiform discharges between VEEG patients in different medication groups(P > 0.05). The total effective rate of treatment in the VEEG epileptiform discharge group was 91.3%,which was significantly lower than that of the VEEG non epileptic discharge group (100%,P < 0.05). The main adverse reactions during treatment were drowsiness , abnormal behavior, abnormal sensation and gastrointestinal reaction. There was no significant difference in monitoring epileptiform discharges between VEEG patients (P > 0.05). All adverse reactions were improved after symptomatic treatment. Conclusion The VEEG plays an important role in guiding the patients with refractory epilepsy for epilepsy typing characteristics and AEDs treatment ,so it has significant correlation to the prognosis , and it also has an important significance in assessing the prognosis.

The study on Notch1 pathway-related tubular formation of glioma cell lines / 中国神经精神疾病杂志

Objective To explore the mechanism of the formation of glioma cells derived vessels (GCDV).Methods The tubular formation assay was performed on 3D cell cultures of U87,U251,U373,SF295,T98G,SKMG-4 and C6 glioma cell lines.The expression of Notch1 、Dll4 were examined by western blot analysis.Result The mean number of vasculogenic channels of cell lines C6,U373,U87,T98G,SF295,U251 and SKMG-4 per area (100×) were 25.2±5.0,36.4±3.2,19.0±2.2,12.6±2.4,4±2.2,0.2±0.4 and 0,respectively.The relative protein densities of Notchl in U87,U251,T98G,SF295,SKMG-4,C6 and U373 were 0.34,0.21,0.79,0.04,0.28,1.75 and 1.19,which were significantly related with the tubular formation ability (P＜0.05).However,the expression of Dll4 was not associated with tubular formation ability (P＞0.05).Conclusion Notch1 may play a key role in tubular formation of glioma cells while the role of Dll4 in the process needs further study.

Effects and mechanisms of receptor-interacting serine-threonine kinase 3 in the formation of cholestatic hepatic injury / 中华消化外科杂志

Objective To investigate the effects and mechanisms of receptor-interacting serine-threonine kinase 3 (RIP3) in the formation of cholestatic hepatic injury.Methods The experimental study was conducted.(1) Processing and viability of hepatic stellate cell line HSC-T6:HSC-T6 cells were transfected by RIP3-siRNA and NC-siRNA,respectively.The viabilities of un-transfected,RIP3-siRNA-transfected and NC-siRNA-transfected HSC-T6 cells were respectively measured by cell-counting kit-8 (CCK-8).HSC-T6 cells were treated by 100 μmol/L Glycochenodeoxycholic acid (GCDCA) at 0,2,4,8 and 12 hours,and then were extracted and stored,12-hour cell viability was measured by CCK-8.RIP3 that was treated by 100 μmol/L GCDCA knocked down HSC-T6 cells to establishment RIP3 knockdown HSC-T6 cells (RIP3-KD cells).RIP3-KD cells were cultured for 12 hours,and cell viability was measured.(2) Mice model of bile duct ligation (BDL):40 adult mice were randomly divided into 8 groups,5 mice in each group.Sham group:bravery manager was only separated,without ligation,and bloods of inferior vena cava and liver tissues were extracted at 7 days postoperatively.The BDL-1,-3,-5,-7,-14,-21 and-28 d groups:bloods of inferior vena cava and liver tissues were extracted at 1,3,5,7,14,21 and 28 days postoperatively,respectively.(3) The relative expressions of RIP3,α-SMA and TNF-αmRNA in the cells and liver tissues were detected by quantitative real-time polymerase chain reaction (RT-PCR).(4) The relative expressions of RIP3,α-SMA and TNF-α proteins were detected by Western blot.Measurement data with normal distribution were represented as-x±s.The ANOVA was used for data analysis in different time gradient.Comparisons among groups were analyzed using the ANOVA.Pairwise comparison was done by the t test.Results (1) The HSC-T6 cells viability and expressions of RIP3,α-SMA,TNF-α mRNA and proteins:results of CCK8 test showed that 12-hour viabilities of GCDCA-treated HSC-T6 cells,GCDCA-treated RIP3-KD cells,HSC-T6 cells and RIP3-KD cells were 61.3％ ±0.3％ and 83.2％ ±0.4％ and 98.4％ ±0.7％ and 97.4％ ±0.7％ respectively,showing statistically significant differences in the viabilities among them (F =115.200,P＜ 0.05),and showing no statistically significant difference in the viabilities between HSC-T6 cells and RIP3-KD cells (t =1.283,P＞ 0.05).There were statistically significant differences in the viabilities between HSC-T6 cells and GCDCA-treated HSC-T6 cells or GCDCA-treated RIP3-KD cells (t =17.910,6.604,P＜ 0.05) and between GCDCA-treated HSC-T6 cells and GCDCA-treated RIP3-KD cells (t=7.186,P＜0.05).Results of RT-PCR test showed relative expressions of RIP3 mRNA in un-transfected,RIP3-siRNA-transfected and NC-siRNA-transfected HSC-T6 cells were respectively 0.012 1±0.001 3,0.011 2±0.003 1 and 0.002 8±0.000 5,with a statistically significant difference (F =20.410,P ＜ 0.05).There was no statistically significant difference in relative expressions of RIP3 mRNA between un-transfected and NC-siRNA-transfected HSC-T6 cells (t =0.483,P ＞0.05).The relative expression of RIP3 mRNA in RIP3-siRNA-transfected HSC-T6 cells was significant different from that in un-transfected and NC-siRNA-transfected HSC-T6 cells (t =11.760,4.586,P＜0.05).The relative expressions of RIP3 mRNA,α-SMA mRNA and TNF-α mRNA in GCDCA-treated HSC-T6 cells at 0,2,4,8 and 12 hours were 0.012 1±0.001 3,0.011 2±0.003 1,0.021 2±0.002 2,0.027 8±0.002 1,0.029 8±0.002 3 and 0.571±0.012,0.611±0.024,0.691±0.021,0.711±0.021,0.752±0.031 and 0.873±0.022,0.912± 0.024,1.015±0.031,1.210±0.042,1.471±0.041,respectively,showing an increased trend over time and statistically significant differences (F=70.720,30.050,166.700,P＜0.05).The relative expressions of RIP3 mRNA in HSC-T6 cells and GCDCA-treated HSC-T6 cells were 0.012 1±0.001 3 and 0.029 8±0.002 3,with a statistically significant difference (t=13.970,P＜0.05).Results of Western blot showed that relative expressions of RIP3 protein in un-transfected,RIP3-siRNA-transfected and NC-siRNA-transfected HSC-T6 cells were respectively 0.054 ± 0.012,0.013 ± 0.008 and 0.052± 0.021,with a statistically significant difference (F =7.410,P＜0.05).There was no statistically significant difference in relative expressions of RIP3 protein between un-transfected and NC-siRNA-transfected HSC-T6 cells (t =0.143,P ＞ 0.05),and statistically significant differences were found in relative expressions of RIP3 protein between RIP3-siRNA-transfected HSC-T6 cells and un-transfected or NC-siRNA-transfected HSC-T6 cells (t =4.924,3.006,P＜0.05).The relative expressions of RIP3,α-SMA and TNF-oα proteins in GCDCA-treated HSC-T6 cells at 0,2,4,8 and 12 hours were 0.045±0.024,0.047±0.034,0.062±0.025,0.121±0.015,0.154±0.034 and 0.064±0.031,0.072±0.017,0.097±0.035,0.078±0.031,0.254±0.051 and 0.078±0.025,0.094±0.037,0.129±0.041,0.198±0.011,0.324±0.061,respectively,showing an increased trend over time and statistically significant differences (F =9.658,15.810,20.090,P＜0.05).The relative expressions of RIP3 protein in HSC-T6 cells and GCDCA-treated HSC-T6 cells at 12 hours were 0.045±0.024 and 0.154±0.034,with a statistically significant difference (t =4.536,P＜0.05).(2) Expressions of RIP3,α-SMA and TNF-α mRNA in hepatic tissues of mice in each group:the results of RT-PCR showed that relative expressions of RIP3 mRNA,α-SMA mRNA and TNF-α mRNA in the Sham,BDL-1 d,BDL-3 d,BDL-5 d,BDL-7 d,BDL-14 d,BDL-21 d,BDL-28 d groups were 0.047 3±0.003 1,0.041 2±0.007 8-0.339 7±0.017 1 and 2.948±0.612,2.654± 1.032-8.387±0.910 and 0.563±0.078,0.610±0.113-1.078± 0.289,respectively,with statistically significant differences (F =25.180,27.820,7.425,P＜0.05).The results of western blot showed that relative expressions of RIP3,α-SMA and TNF-α proteins in Sham,BDL-1 d,BDL-3 d,BDL-5 d,BDL-7 d,BDL-14 d,BDL-21 d,BDL-28 d groups were 0.245±0.011,0.228±0.023-1.018±0.052 and 0.424±0.057,0.392±0.041-0.985±0.081 and 0.551 ±0.052,0.588±0.087-0.962±0.074,respectively,with statistically significant differences (F=19.160,94.410,22.750,P＜0.05).Conclusion Cholestasis promotes hepatic injury and fibrosis by inducing TNF-α pathway activation and upregulation RIP3.

Cartilaginous tumors of the cricoid: a case report / 临床耳鼻咽喉头颈外科杂志

Review a case of cricoid cartilaginous tumour in our hospital in December 2013 retrospectively, which received laryngofissure surgery and was followed up for 1 year. The case is still alive without recurrence. The incidence of laryngeal cartilaginous tumour is low, most are cases of cricoid cartilaginous tumour. Try to preserve laryngeal function in surgery as much as possible.

Combined detection of serum DKK1 and P53 autoantibodies for the diagnostic value of esophageal squa-mous cell carcinoma / 国际肿瘤学杂志

Objective To evaluate the diagnostic value of the combination of serum DKK1 (Dickkopf-1 )and P53 autoantibodies in patients with esophageal squamous cell carcinoma (ESCC).Methods Serum levels of DKK1 and P53 autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA) for the 1 26 patients with ESCC and 60 normal controls.Receiver operating characteristics (ROC)was used to calculate the diagnostic efficiency.Results The serum levels of DKK1 and P53 autoantibodies were signifi-cantly higher in ESCC than those in normal controls [(673.09 ±343.82)pg/ml vs (362.05 ±1 48.07)pg/ml, Z =6.1 58,P <0.000 1 ;(0.398 ±0.546)vs (0.069 ±0.050),Z =3.832,P <0.000 1 ].ROC curves showed the optimum diagnostic cutoff for serum DKK1 was 588.77 pg/ml,with an area under curve (AUC)of 0.780 (95%CI:0.71 5 ~0.844,61 .9% sensitivity,95.0% specificity).Measurement of P53 autoantibodies demonstrated an AUC of 0.674 (95%CI:0.598 ~0.750,45.3% sensitivity,95.0% specificity).The com-bination of DKK1 and P53 autoantibodies yielded an AUC of 0.843 (95%CI:0.788 ~0.897,73.8% sensitiv-ity,95.0% specificity).In early-stage ESCC,combined detection of DKK1 and P53 autoantibodies improved the diagnostic power,with an AUC of 0.903 (95%CI:0.845 ~0.961 ,81 .0% sensitivity,95.0% specifici-ty).Conclusion Serum DKK1 and P53 autoantibodies can be used as potential diagnostic biomarkers for the ESCC.Combined detection of them might aid the early diagnosis of ESCC.

Transverse fascia repair with fishing net methods for inguinal hernia under laparoscopic / 中国医师进修杂志

Objective To explore the feasibility of fishing net repairing transverse fascia method for inguinal hernia (type Ⅰ , Ⅱ ) using laparoscopic surgical procedure. Methods A retrospective analysis of clinical data between the method of fishing net repairing transverse fascia surgery for 145 cases of inguinal hernia (typeⅠ,Ⅱ ) using laparoscopic surgical procedure from May 2004 to May 2008 (laparoscopic group) and the method of open repairing surgery 143 cases (open group) at the same period were conducted. The differences in the operative time, rehabilitation activities time, length of stay, cost of hospitalization and 0comphcations, recurrence rate were compared. Results The laparoscopic group was significantly better in the operative time [ ( 14.8 ± 11.5) min ], found hiding oblique hernia ( 15 cases), rehabilitation activities time[ ( 16.5 ± 14.3) h], use of analgesics(5 cases), scrotal edema(1 case), length of stay[ (4.2 ± 1.5) d], than those of the open group [ ( 37.6 ± 25.4) min, 0, (52.7 ± 12.6) h, 13, 14, ( 8.4 ± 2.6 ) d respectively ] ; but the recurrence rate was no significantly different. Conclusion Method of fishing net repairing transverse fascia for inguinal hernia (type Ⅰ , Ⅱ ) using laparoscopie surgical procedure is feasible.

Effect of hypertensive agent on regional cerebral blood flow in patients with hypertensive intracerebral hemorrhage / 中华急诊医学杂志

Objective To investigate effects of hypertensive agents on regional cerebral blood flow (rCBF)and prognosis in patients with hypertensive intracerebral hemorrhage (HICH). Method Thirty patients withFILCH were divided into group A,B and C according to mean arterial pressure(MAP) with various ranges of <10%, 10 ～ 20%, and > 20%, respectively. Patients of three groups were checked with single photon emissioncomputed tomography (SPECT),and computerized tomography of head successively, 24 hours, 3 ～ 5 days, and 12～ 15 days after admission for the assessment of therapeutic effects. The rtes of the decrease in rCBF compared be-twecn groups were analyzed with t test. Neurologic function defect scale, activities of living scale and number of re-bleeding compared between two groups were analyzed by X2 test, respectively. Results There were statisticallysignificant differences in the rate of the decrease in rCBF. The neurologic function defect scale and activities of liv-ing scale at 24 hours, 3 ～ 5 days, and 12 ～ 15 days after admission compared between group C and group A, andbetween group C and group B showed significant differences ( P < 0.05). There were statistically significant differ-enees in rebleeding during acute phase of HICH between group A and group B or group C (P < 0.05).Conclusions If the systolic blood pressure is above 185mmHg or diastolic blood pressure over 95mmHg,it is ra-tional and safe to lower the MAP by about 15% with hypotensive gents so as to minimize the impact on regionalcerebral blood flow.

Minimally Invasive Surgery Treatment with Small Incision on Hypertensive Intracerebral Hemorrhage / 中国医师杂志

Objective To explore the principle and methods of normative minimally invasive surgery treatment on hypertensive intracerebral hemorrhage. Methods 49 cases of hypertensive intracerebral hemorrhage were treated by microsurgery with small incision. Results 46 cases survived and 3 cases died after surgery. 42 cases were followed up. Adopting GOS, 19 cases were normal, 12 cases were disable and could care for self, 5 cases were severely disable, sober and could not care for self, 3 cases were vegetable survival, and 3 cases were dead. Conclusion Application of minimally invasive surgery idea and normative treatment according to the patients' condition can obviously improve the efficacy of patients with hypertensive intracerebral hemorrhage.

Inhibitory effect of IL-10 on induced expression of ICAM-l in renal tubular cells is mediated by down regulated activity of nuclear factor kB / 中华肾脏病杂志

Objecive To explore the effect of interleukin-10(IL10) on tumor necrosis factor-?(TNF?)- induced expression of intercellular adhesion molecule 1 (ICAM-1 )and related transcription pathway in human renal tubular cells. Methods Human renal proximal tubular cell line HK-2 cell was used as target cell. ICAM-1 was measured by cell ELISA and Northern blot in protein and mBNA levels. Activities of transcriptional factors nuclear factor GB(NFkB) and activator protein 1 (AP-1) were determined by electrophoresis mobility shift assay. Results TNF?-induced ICAM-l expression in HK-2 cells was increased in both protein and mNRA levels(P