[Effect of growth hormone supplementation on liver and lung function in patients with hypopituitarism].

To analyze the clinical features of patients with anterior hypopituitarism (HP) complicated with cirrhosis, and to explore the effects of growth hormone supplementation on liver and lung function. A total of 11 patients with HP complicated with cirrhosis admitted to Peking Union Medical College Hospital from January 2016 to December 2022 were included in the study, including 8 males and 3 females, aged [M(Q1, Q3)]31 (20, 37) years. There were 6 patients with pituitary stalk interruption syndrome, 4 patients after craniopharyngioma resection, and 1 patient after germinal cell tumor chemoradiotherapy. Cirrhosis appeared at [M(Q1, Q3)]7 (1, 16) years after the diagnosis of HP. There were 7 cases complicated with hepatopulmonary syndrome (HPS). The liver and lung function of 5 patients were improved significantly after the addition of growth hormone, and the arterial partial pressure of oxygen increased from (47±11) mmHg(1 mmHg=0.133 kPa) to (84±12) mmHg. Timely supplementation of growth hormone can improve the symptoms of fatty liver, cirrhosis and HPS, and postpone or even avoid the transplantation of liver and other organs.

[Clinical characteristics of Danon disease].

Objective: To review the clinical data of 7 patients with Danon disease and analyze their clinical characteristics. Methods: The medical records of 7 patients with Danon disease, who were hospitalized in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from April 2008 to July 2021, were reviewed and summarized, of which 6 cases were diagnosed as Danon disease by lysosomal-associated membrane protein-2 (LAMP-2) gene mutation detection and 1 case was diagnosed by clinicopathological features. Clinical manifestations, biochemical indexes, electrocardiogram, echocardiography, skeletal muscle and myocardial biopsy and gene detection results were analyzed, and patients received clinical follow-up after discharge. Results: Six patients were male and average age was (15.4±3.5) years and the average follow-up time was (27.7±17.0) months. The main clinical manifestations were myocardial hypertrophy (6/7), decreased myodynamia (2/7) and poor academic performance (3/7). Electrocardiogram features included pre-excitation syndrome (6/7) and left ventricular hypertrophy (7/7). Echocardiography examination evidenced myocardial hypertrophy (6/7), and left ventricular dilatation and systolic dysfunction during the disease course (1/7). The results of skeletal muscle biopsy in 6 patients were consistent with autophagy vacuolar myopathy. Subendocardial myocardial biopsy was performed in 3 patients, and a large amount of glycogen deposition with autophagosome formation was found in cardiomyocytes. LAMP-2 gene was detected in 6 patients, and missense mutations were found in all these patients. During the follow-up period, implantable cardioverter defibrillator implantation was performed in 1 patient because of high atrioventricular block 4 years after diagnosis, and there was no death or hospitalization for cardiovascular events in the other patients. Conclusion: The main clinical manifestations of Danon disease are cardiomyopathy, myopathy and mental retardation. Pre-excitation syndrome is a common electrocardiographic manifestation. Autophagy vacuoles can be seen in skeletal muscle and myocardial pathological biopsies. LAMP-2 gene mutation analysis is helpful in the diagnose of this disease.

[Using the external auditory canal skin graft of the healthy side to treat unilateral congenital aural atresia: preliminary results of clinical research].

Objective: To investigate whether the contralateral normal external auditory canal (EAC) skin graft can maintain the ear canal health after EAC reconstruction in unilateral congenital aural atresia (CAA) cases. Methods: A Zelen design randomized controlled study was used to collect unilateral CAA patients for EAC reconstruction prospectively (clinical trial registration number: ChiCTR2000032103). The patients were randomly divided into the control group and the trial group. The trial group used the contralateral normal EAC skin graft group (transplant part of the contralateral normal EAC skin to repair the atresia side for unilateral CAA patients), the control group all used scalp blade thick skin. We observed the EAC health and hearing results of the two groups after EAC reconstruction. Results: A total of 13 cases were enrolled from July 2020 to August 2021. There were eight patients in the trial group, including six males and two females, with an average age of 22.3 years (14-36 years). There were two patients with CAA on the left and six patients on the right. The average follow-up time was 8.8 months (4-14 months). There were five patients in the control group, all cases were male with an average age of 16.2 years (12-20 years). There were four patients with CAA on the left and one patient on the right. The average follow-up time was 7.0 months (2-14 months). In the trial group, eight cases of reconstructed EAC epithelium were healthy, one patient had cicatricial stenosis of EAC opening and lateralization of the tympanic membrane. The other patient had cicatricial stenosis of reconstructed EAC, this case also had scar hyperplasia of the contralateral EAC opening but recovered after soft packing and triamcinolone acetonide injection treatment. The healthy side EAC of the rest trial group had no scarring stenosis or local bone hyperplasia during long-term follow-up. In the control group, one patient was lost to follow-up and the other four patients had dry ears of reconstructed EAC, but easily to form crusts and needed to be cleaned repeatedly, one patient had lateralization of the tympanic membrane, the EAC epithelium was not healthy for long-term follow-up. The incidence of complications related to EAC reconstruction was lower than previous studies (χ²=5.55, P=0.018), and the average postoperative Air-Bone Gap increased (18.8±10.0)dB. Conclusion: By optimizing the EAC reconstruction technology, the health of the reconstructed EAC is improved compared with the previous study. After active intervention and treatment, there should be no scarring stenosis or local bone hyperplasia on the contralateral side EAC.

[Effect evaluation of surgical plus radio(chemo)therapy and non-surgery chemoradiotherapy treatment strategies for advanced tonsillar squamous cell carcinoma].

Objective: Using propensity score matching method(PSM) to investigate the clinical effect of surgical plus radio(chemo)therapy and non-surgery chemoradiotherapy treatment strategies for advanced tonsillar squamous cell carcinoma. Methods: A retrospective analysis was conducted on the clinical data of 324 patients diagnosed with advanced tonsillar squamous cell carcinoma and treated in Peking Union Medical College Hospital from 2000 to 2018, confirmed by pathology and without distant metastasis. Survival analysis was performed using Kaplan-Meier estimates, the Cox proportional hazards model, and propensity score matching(PSM). Results: Of the 324 patients, 102 were treated with non-surgery chemoradiotherapy treatment strategies and 222 with surgical plus radio(chemo)therapy treatment. Cox multivariate analysis showed that the non-surgery treatment group had a favorable prognosis than the surgical treatment group, however, these outcomes were not significantly different [overall survival(OS): adjusted Hazard Ratios(aHR): 0.92, 95% confidence interval(CI): 0.60-1.42; disease-specific survival(DSS): aHR: 0.71, 95%CI: 0.43-1.20; disease-free survival(DFS): aHR: 0.82, 95%CI: 0.53-1.28]. The new patient cohort consisted of 102 subpairs after PSM. There were no significant differences between two groups(OS: aHR: 0.85, 95%CI: 0.51-1.40; DSS: aHR: 0.62, 95%CI: 0.35-1.11; DFS: aHR: 0.80, 95%CI: 0.49-1.33). Conclusion: Our findings indicate that patients with non-surgical treatment do not have significantly better survival outcomes compared to surgical treatment group, while non-surgical treatment has advantages in improving the quality of life of patients, so comprehensive treatment based on radiotherapy and chemotherapy may be recommended for advanced tonsillar squamous cell carcinoma.

[Application of dual-channel contrast-enhanced ultrasound in classification of hilar cholangiocarcinoma and diagnosis of etiology of low biliary obstruction].

Objective: To investigate the clinical value of dual-channel contrast-enhanced ultrasound (DCUS) in the classification of hilar cholangiocarcinoma and the diagnosis of the etiology of low obstructive jaundice. Methods: The data of 114 patients with obstructive jaundice examined by the Department of Ultrasound of Lanzhou University Second Hospital from October 2018 to February 2020 were retrospectively collected. There were 60 males and 54 females, aged 37~84 (63±10) years. All patients underwent preoperative transvenous contrast-enhanced ultrasound (CEUS), intraoperative puncture needles, postoperative ultrasound-guided percutaneous transhepatic cholangiocarcinography (UG-PTC) and three-dimensional ultrasound cholangiography (3D-USC) through an external drainage tube, known as DCUS. The classification of hilar cholangiocarcinoma and the nature of low biliary tract obstruction were determined according to the characteristics of DCUS images. All patients who have received DCUS underwent magnetic resonance cholangiopancreatography (MRCP) and X-ray cholangiography. X-ray cholangiography was used as the gold standard for classification of hilar cholangiocarcinoma, and the accuracy of US, CEUS and DCUs was analyzed. Low obstructive jaundice was characterized by surgical pathology as the gold standard, and the diagnostic efficacy of conventional ultrasound (US), CEUS and DCUs was analyzed. At the same time, the receiver operating characteristic (ROC) curve was used to compare the efficacy of MRI+MRCP and DCUS in determination of the nature of low biliary obstruction. Results: The coincidence rates of US, CEUS, and DCUS in the classification of hilar cholangiocarcinoma and X-ray cholangiography were: 75.6% (34/45), 82.2% (37/45), and 93.3% (42/45), respectively. The coincidence rates of US, CEUS, and DCUS in the determination of the nature of low biliary obstruction and surgical pathology were 56.5% (39/69), 82.6% (57/69), and 85.5% (59/69), respectively. Compared with conventional ultrasound, CEUS had no statistically significant difference in the diagnosis of hilar cholangiocarcinoma (P=0.438), and DCUS had statistically significant difference in the diagnosis of hilar cholangiocarcinoma (P=0.039).ROC curve analysis suggested that the cut-off value of MRI+MRCP grade and DCUS grade for diagnosing benign and malignant low biliary obstruction were both 2.5; the area under the curve (AUC) were 0.897 and 0.906, respectively (both P<0.01); sensitivity were 77.5% and 93.1%, respectively; and the specificity were 87.5% and 82.8%, respectively. Conclusion: The value of DCUS in the classification of hilar cholangiocarcinoma and the qualitative diagnosis of low biliary tract obstruction was comparable to that of X-ray cholangiography and MRCP. DCUS had important clinical application value in the classification of hilar cholangiocarcinoma and the etiological diagnosis of low obstructive jaundice.

[Effect of topical injection of cyclosporine A on saliva secretion and inflammation in the submandibular gland of non-obese diabetic mice].

OBJECTIVE: To investigate the effects of topical administration of cyclosporine A (CsA) on salivary secretion and inflammation of the submandibular glands in non-obese diabetic (NOD) mice. METHODS: Female NOD mice, 21 aged 14 weeks and 18 aged 21 weeks were selected and randomly divided into low-dose group, high-dose group and control group on average. CsA was injected into submandibular glands. One week later the saliva stimulated by pilocarpine was collected and measured. The submandibular glands were collected to make paraffin sections. The lymphocyte infiltration in submandi-bular gland was observed by microscope after hematoxylin-eosin (HE) staining. The number of lymphocyte infiltration foci was counted to calculate the focus sore and the ratio of lymphocyte infiltration area to total gland area was figured up by Leica image analysis system. The expressions of inflammatory cytokines tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-13, IL-17F, IL22 and IL-23a in the submandibular glands of the NOD mice were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell apoptosis in the submandibular gland was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The levels of serum creatinine (Scr), blood urea nitrogen (BUN), uric acid (UA), alanine aminotransferase (ALT), aspertate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB) and γ-glutamyl transferase (GGT) were measured by automatic biochemical analyzer to evaluate liver and kidney functions. RESULTS: After topical injection of CsA in the submandibular gland, the stimulated salivary flow rate of the 14- and 21-week-old NOD mice significantly increased compared with the control group (P < 0.01 or P < 0.05), and the number and area of lymphocyte infiltration foci in the 14-week-old NOD mice low-dose group significantly decreased compared with the control group (P < 0.01). Low and high dose of CsA had similar effects on reducing inflammation and improving salivary secretion. The overall level of inflammatory cytokines in the submandibular gland did not decrease significantly. The number of cell apoptosis of submandibular gland in the NOD mice treated with CsA decreased compared with the control group, but there was no statistically significant difference. Topical injection of CsA had no adverse effect on liver and kidney function in the NOD mice. CONCLUSION: Topical injection of CsA can reduce lymphocyte infiltration in submandibular gland of NOD mice and improve salivary secretion.

[Clinical and imaging characteristics of patients with primary cardiac angiosarcoma].

Objective: To investigate the clinical, cardiac imaging characteristics and prognosis of patients with primary cardiac angiosarcoma. Methods: The clinical data of 14 patients hospitalized with primary cardiac angiosarcoma from January 2001 to December 2017 in Peking Union Medical College Hospital were collected and analyzed. Metastatic cardiac angiosarcoma was not included in this study. Patients were followed up post discharge per telephone call or clinical visit. Results: Of the 14 patients, 8 were males and 6 were females, average age was 48 years. The main clinical symptoms were shortness of breath (8/14), hemoptysis (6/14), fever (5/14), chest pain (4/14) and cough (3/14). Imaging examinations showed that the tumors of 8 patients were located in the right heart and 6 in the pericardial cavity. Tumors in the right heart often infiltrate the atrial wall and cause pericardial effusion (7/8). Tumors in the pericardium were characterized by recurrent bloody pericardial effusion (6/6), prone to progressive constrictive pericarditis (3/6), pericardial fluid cytology was often negative (6/6). MRI showed heterogeneous high signal intensity (cauliflower aspect) on T2-weighted image and heterogeneous enhancement with a"sunray" aspect at the perfusion study. At the time of diagnosis, 8 patients developed lung or adrenal metastasis (8/14). The median survival was only 305 days. Conclusions: Primary cardiac angiosarcoma is a rare disease with non-specific clinical manifestation and poor prognosis. Imaging examinations may help diagnosis. The high invasiveness and the easy-to-metastasis feature of the tumor contribute to the poor prognosis of cardiac angiosarcoma.

[Molecular epidemiological characteristics of methicillin-resistant Staphylococcus aureus during 2017-2018 at a hospital in Shanghai].

Objective: To identify the epidemic clones of MRSA isolates at a hospital in shanghai. Methods: A total of 72 MRSA isolates have been isolated from a second grade hospital between 2017 and 2018, including 32 CA-MRSA isolates, 13 HA-MRSA isolates and 26 MRSA isolates from environment. In this study, MLST and PFGE typing methods were used to analyze the molecular epidemiology of the MRSA isolates. Results: A total of 72 MRSA isolates have been obtained including 46 isolates from clinical specimens, 26 isolates from environments. The 46 MRSA isolates from clinical specimens consisted of 33 CA-MRSA (community-acquired MRSA) and 13 HA-MRSA (hospital-acquired MRSA). Furthermore, these patients infected with MRSA isolates were mostly distributed in the department of geriatrics (34.8%, 16/46), internal medicine (26.1%, 12/46) and surgery (26.1%, 12/46). MLST typing results showed that ST764 was predominant in isolates from both clinical specimens and hospital environments. Furthermore, PFGE typing results showed that most ST764 MRSA had high homolog (>90%). Conclusion: ST764 MRSA isolates might spread in community, hospital and environments. Therefore, continuous monitoring of MRSA and its variation may be useful in understanding the involvement of epidemic clone, and in searching new strategies to control MRSA infection.

[Correlation between interleukin-6 single nucleotide polymorphism and the occurrence and prognosis of hepatitis B virus-associated acute-on-chronic liver failure].

Objective: To investigate the correlation between interleukin-6 (IL-6) single nucleotide polymorphism (SNP) and the occurrence and prognosis of hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). Methods: Patients with chronic hepatic diseases diagnosed as HBV infection in the Hepatology Center of the First Affiliated Hospital of Fujian Medical University from July 2012 to March 2018 were divided into HBV-ACLF and non-ACLF group. SNP genotyping of eight loci in IL-6 gene (rs1524107, rs1800795, rs1800797, rs2069827, rs2069830, rs2069837, rs2069840 and rs2069845) was determined by the improved multi-temperature ligase detection reaction (imLDRTM) technique. Simultaneously, case data were reviewed with the 3-months followed up survival condition of the ACLF group. Normally distributed data were expressed as arithmetic means and SDs, and t-test was adopted. Data with skewed distribution were expressed as medians with interquartile range, and were measured by non-parametric test. Multivariate logistic regression analysis was used to analyze the relative risk of genetic polymorphism and HBV-ACLF as well as the relationship between IL-6 SNPs with the occurrence and prognosis of HBV-ACLF. Results: Four hundred patients were included in the study, with 122 (30.5%) in the HBV-ACLF and 278 (69.5%) in the non-ACLF group. There were significant differences in total bilirubin, albumin, and white blood cell count, percentage of neutrophils, platelet count, alanine aminotransferase, aspartate aminotransferase, prothrombin time and international standardized ratio, creatinine and the model for end-stage liver disease score between the two groups (P < 0.001). The genotype of IL-6 genes (rs1800795, rs1800797, rs2069827, and rs2069830) of all subjects showed no mutation or the mutation rate under 1%. There was no significant difference in the genotype of IL-6 (rs1524107, rs2069837, rs2069840 and rs2069845) between the two groups (P > 0.05). Multivariate logistic regression analysis showed that the SNPs in the above four loci of IL-6 gene was not associated with HBV-ACLF risk, nor had significant correlation with the 3-months prognosis. Conclusion: The SNP genotyping of eight loci in IL-6 gene (rs1524107, rs1800795, rs1800797, rs2069827, rs2069830, rs2069837, rs2069840 and rs2069845) is unrelated to the occurrence and short-term prognosis of HBV-ACLF.

[Clinical features of mucosa-associated lymphoid tissue lymphoma in head and neck].

Objective:To summarize the clinical features, diagnosis and treatment of mucosa-associated lymphoid tissue(MALT) lymphoma in head and neck. Method:The clinical data of 22 hospitalizedpatients with MALT lymphoma in head and neck during the recent 18 years were analyzed retrospectively. Result: Among the 22 cases, 13 patients showed salivary gland lesions, 4 showed larynx and trachea lesions,3 showed nasopharynx lesions and 2 showed thyroid gland lesions. The clinical manifestation was occupying or compression. Among them,12 patients received chemotherapy or chemoradiotherapy,5 received surgery plus chemotherapy,3 received surgery plus radiotherapy, 1 received surgery alone and 1 received radiotherapy alone; complete response(CR) occurred in 15 patients, partial response(PR) occurred in 6 patients, and 1 was stable disease(SD). The mean follow-up time was 92(8-211) months. During the follow-up period, 18 patients survived, 4 died, the three year progression free survival(PFS) and overall survival(OS) were both 95.2%, and the fiveyear PFS and OS were 79.4% and 89.6% respectively. Conclusion:The prognosis of MALT lymphoma in head and neck was good. MALT lymphoma has no specific clinical manifestations. Chemotherapy was the main treatment. Local treatment can be conducted for patients with localized lesions. .

[Congenital pyriform fistula with acute suppurative thyroiditis as the initial presentation].

Objective: To summarize the clinical characteristics of congenital pyriform fistula with acute suppurative thyroiditis as the initial presentation. Method: A total of 71 patients with congenital pyriform sinus fistula were treated, of which 33 cases had acute suppurative thyroiditis as the first symptom. For the patients with congenital pyriform sinus fistula who have acute suppurative thyroiditis as the first symptom, infection should be controlled first. Full drainage should be done when necessary, and the lesion should be completely excised during the stable period. Result: All the patients were followed up for 6 months to 216 months. No recurrence was found during follow-up. Conclusion: For patients with acute suppurative thyroiditis, the possibility of congenital pyriform sinus fistula should be considered.If the diagnosis of congenital pyriform sinus fistula is clear,the lesion should be completely resected by surgery. .

[Proliferation and apoptosis of lung cancer cells regulated by gultaredoxin 3].

Objective: To investigate the effects of inhibiting glutaredoxin 3(GLRX3) expression on proliferation and apoptosis of lung cancer cells. Methods: Western blotting was used to detect the expressions of GLRX3 protein in human embryonic lung fibroblast MRC5 and lung cancer cells, including A427, A549, PC9 and H1299. GLRX3-targeted siRNA (experimental group) and negative siRNA (negative group) were transfected into A549 cells, and the cells without special treatment were blank group. The protein expression levels of GLRX3, cleaved cysteinyl aspartate specific proteinase 3(cleaved caspase-3), signal transducers and activators of transcription 3(STAT3), phosphorylated STAT3(p-STAT3) in each group at 48 hours after transfection were measured by Western blotting. The proliferation ability of differently treated cells at 24 hours, 48 hours and 72 hours after transfection were detected by CCK-8 array. The cell apoptosis at 48 hours after transfection was evaluated by flow cytometry. Results: The protein expression levels of GLRX3 in MRC5, A427, A549, PC9 and H1299 were 0.094±0.010, 0.282±0.021, 0.551±0.045, 0.423±0.039 and 0.454±0.036, respectively. The protein expressions of GLRX3 in tested lung cancer cells were significantly higher than that of MRC5 cells (all P<0.01). The GLRX3 protein expressions in blank group, negative control group and experimental group at 48 hours after transfection were 0.311±0.029, 0.328±0.032 and 0.103±0.012, respectively. GLRX3 protein expression level of experimental group in A549 cells was significantly lower than that of control group (P<0.01), whilewithout statistical difference between the negative group and blank group (P>0.05). A values of experimental group at 24, 48 and 72 hours after transfection in A549 cells were significantly different from those of blank group (all P<0.01). Percent of apoptotic cells in the experimental group was (9.52±0.56)%, which was significantly higher than that of blank group [(1.65±0.22)%] and negative control group [(1.42±0.26)%, all P<0.01]. Consistently, compared with blank group, the cleaved caspase-3 markedly increased in the experimental group (P<0.01). The protein expression of p-STAT3 in the experimental group was significantly lower than the blank group (P<0.01), while no significant difference of STAT3 protein expression was observed among all the groups (P>0.05). Conclusions: Inhibition of GLRX3 gene expression can inhibit the proliferation of lung cancer cells and induce cell apoptosis through up-regulating cleaved caspase-3 expression and down-regulating STAT3 signaling pathway.

[Decreased phosphorylation of mitogen activated protein kinase and protein kinase B contribute to the inhibition of osteogenic differentiation mediated by activation of Toll like receptor in human periodontal ligament stem cells].

OBJECTIVE: To investigate the effects of Toll like receptors on the osteogenesis of human pe-riodontal ligament stem cells (hPDLSCs) and probable molecular mechanism. METHODS: Real-time PCR and flow cytometry were applied to test the expression of TLRs in hPDLSCs and the positive cell percentage of TLR. hPDLSCs were cultured in osteogenic medium for 7 to 14 days with different TLR agonists at various concentrations . The effect of different TLR on osteogenic differentiation of hPDLSCs was evaluated by alizarin red S staining, alkaline phosphatase (ALP) staining and ALP activity assay. Western blotting was used to analyze the phosphorylation levels of extracellular regulated protein kinases (ERK), c-Jun N-terminal protein kinase (JNK), P38, AKT and expression of Runx2 an osteogenic related gene after treatment with TLR agonists, compared with the effect of inhibitors of mitogen activated protein kinase (MAPK) or protein kinase B (PKB or AKT) on Runx2 expression of hPDLSCs cultured in osteogenic medium. RESULTS: Higher expressions of TLR1,3,4,6 were found in hPDLSCs through real-time PCR. Positive cell percentage of TLR was determined by flow cytometry and described as TLR1: 2.82%±0.68%; TLR2: 1.26%±0.09%; TLR3: 13.23%±2.05%; TLR4: 3.64%±0.79%; TLR6: 3.21%±1.64%, whose tendency was comparable to their mRNA expression in hPDLSCs. Most TLR ligands had no effect on the ALP staining, activity and mineralization of hPDLSCs at lower concentration except for 0.1 mg/L PolyI:C could induce the osteogenic ability of hPDLSCs. On the contrary, Higher concentration of TLR ligands (PolyI:C: 10 mg/L, LPS: 10 mg/L , Pam3CSK4: 1 mg/L, FSL-1: 50 µg/L) had obviously inhibitory effect on osteogenic differentiation of hPDLSCs. Activation of TLR using higher concentration of TLR ligands could downregulate the phosphorylation levels of ERK, P38, JNK and AKT, and also reduced the expression of Runx2, compared with the untreated control. The inhibitors of MAPK (U0126, SP600125,SB203580) and inhibitor of AKT (perifosine) could also inhibit Runx2 expression. CONCLUSION: Higher concentration of TLR ligands could inhibit osteogenic differentiation of hPDLSCs. This inhibitory effect seemed to be related to decreased phosphorylation of MAPK and AKT.

[The effect of WT1 expression on the prognosis of allogeneic hematopoietic stem cell transplantation in acute leukemia].

Objective: To study the effect of WT1 expression on the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute leukemia (AL) and its significance as molecular marker to dynamically monitor minimal residual disease (MRD) . Methods: Retrospectively analyzed those AL patients who underwent allo-HSCT in the First Hospital Affiliated to Zhejiang University School of Medicine during Jan 2016 to Dec 2017, a total number of 314 cases, 163 males and 151 females, median age was 30 (9-64) years old. Comparing the difference of WT1 expression at diagnosed, pre-HSCT and after HSCT. Using the receiver operating characteristic (ROC) curve to determine the WT1 threshold at different time so as to predict relapse. The threshold of WT1 expression before transplantation was 1.010%, within 3 months after HSCT was 0.079% and 6 months after HSCT was 0.375%. According to these thresholds, WT1 positive patients were divided into low expression groups and high expression groups. Analyzed the relationship between overall survival (OS) , disease-free survival (DFS) , cumulative incidence of relapse (CIR) and WT1 expression. Results: The OS and DFS of high expression group pre-HSCT were lower than low expression group [69.2% (9/13) vs 89.1% (57/64) , χ(2)=4.086, P=0.043; 53.8% (7/13) vs 87.5% (56/64) , χ(2)=9.766, P=0.002], CIR was higher than low expression group [30.8% (4/13) vs 7.8% (5/64) , P=0.017]. There was no significant difference of OS and DFS between high expression and low expression group of 3 months after HSCT (P=0.558, P=0.269) . The OS and DFS of high expression group of 6 months after transplantation were both lower than low expression group (P=0.049, P=0.035) . Multivariate analysis showed that WT1>0.375% when 6 months after transplantation was the only independent prognostic factor for shorter DFS (P=0.022) . There was no statistically significant difference in CIR between the high-expression group and the low-expression group 3 months after transplantation and 6 months after transplantation (P=0.114, P=0.306) . Conclusion: High expression of WT1 before and after HSCT was an adverse prognosis factor. It is of clinical practical value to use WT1 as a transplant recommendation index for patients with acute leukemia and as a marker to monitor MRD dynamically.