Progress of leukemia with NUTM1 gene rearrangement / 白血病·淋巴瘤

Molecular typing of leukemia is the basis of risk assessment and treatment options. NUTM1 gene (15q14) rearrangement is a novel molecular type of acute B lymphoblastic leukemia (B-ALL), which is mainly found in children (≥1 year old) and infants (< 1 year old). The number of patients is slightly more in children than infants. However, in infantile ALL, NUTM1 rearrangement is the second most common molecular abnormality. These children respond well to conventional chemotherapy regimens and with a good prognosis. The number of leukemia patients with NUTM1 gene rearrangement is still small, and there is no relevant study or case report in China. NUT protein encoded by NUTM1 gene is a chromatin regulator, which is related to histone acetylation regulation and chromatin remodeling. This article aims to introduce the clinicopathological features, detection methods, possible tumorigenic mechanisms and therapeutic prospects of leukemia with NUTM1 gene rearrangement, to increase the understanding of this type of leukemia and provide reference for the precise molecular subtyping and treatment.

Retroperitoneal dedifferentiated liposarcoma with rhabdomyoblastic differentiation: a clinicopathological analysis / 中华病理学杂志

Objective@#To investigate the clinicopathological features, differential diagnosis, treatment and prognosis of dedifferentiated liposarcoma with rhabdomyoblastic differentiation.@*Methods@#Six cases of retroperitoneal dedifferentiated liposarcoma with rhabdomyoblastic features were collected from December 2014 to August 2017 at Peking University International Hospital. The clinical manifestations, histomorphology, immunophenotype, treatment and follow-up data were analyzed, and relevant literature reviewed.@*Results@#The six patients included two males and four females, with age range of 47 to 66 years (mean 56 years). One case was primary and the five cases were recurred; four cases received radiotherapy and/or chemotherapy. The tumor diameters were 10 to 30 cm. Microscopically, the dedifferentiated areas were well demarcated from the well-differentiated areas, and resembled malignant fibrous histiocytoma, fibrosarcoma or solitary fibrous tumor with obvious mitotic figures or necrosis. Rhabdomyoblastic cells made up 10% to 30% of dedifferentiated area, and were scattered or focally distributed, being rounded, band-like or spindled, mostly with abundant eosinophilic cytoplasm. No striated structure was found, and the nucleis were rounded, oval or irregular shape with central or eccentric prominent nucleoli. Rare rhabdomyoblastic cells were lymphocytoid. The tumors encroached the muscular layer of intestinal wall in two cases and perirenal adipose tissue in one case. By immunohistochemical staining, the rhabdomyoblastic cells of all cases were all positive for desmin, myogenin, myoD1 and SMA; S-100 protein was expressed in one case (1/6). Well-differentiated area in two cases and dedifferentiated areas in all six cases were positive for MDM2, CDK4 and p16. After resection of the tumor and adjacent organs, one case recurred three months later, but there was no distant metastasis.@*Conclusions@#Dedifferentiated liposarcoma with rhabdomyoblastic differentiation is a rare dedifferentiated liposarcoma. Pathological diagnosis is based on morphology, with supplementary immunohistochemical or molecular evaluation for further differential diagnosis. Multiple relapses may occur after surgical ablation plus adjuvant therapy.

Factors associated w ith unfavorable outcome in minor ischemic stroke / 国际脑血管病杂志

ObjectiveToinvestigatetheriskfactorsforunfavorableoutcomeinpatientswithminor ischemic stroke. Methods Patients with minor ischemic stroke were enroled prospectively. The modified Rankin Scale ( mRS ) w as used to assess the clinical outcome at day 90 after onset, and mRS 0-2 w as defined as favorable outcome. The demographic data, vascular risk factors, clinical data, imaging data, stroke etiologic subtypes, laboratory test results, and treatment methods in the favorable outcome group and unfavorable outcome group w ere compared. Multivariate logistic regression analysis w as used to identify the independent risk factors for early poor outcome in patients w ith minor ischemic stroke. Results A total of 516 patients with minor ischemic stroke were enroled. At day 90 after onset, 90 patients (17.44%) had unfavorable outcome and 426 (82.56%) had favorable outcome. Multivariate logistic regression analysis showed that age (odds ratio [OR] 1.045, 95% confidence interval [CI] 1.017-1.074; P=0.002), heart diseases (OR 2.021, 95%CI 1.063-3.841; P=0.032), baseline National Institutes of Health Stroke Scale (NIHSS) score (OR 1.662, 95%CI 1.177-2.347; P=0.004), limb movement disorder ( OR 2.430, 95%CI 1.010-5.850; P=0.048), ataxia (OR 2.929, 95%CI 1.188-7.221;P=0.020), early neurological deterioration ( OR 50.994, 95%CI 17.659-147.258; P<0.001), infarct diameter ( OR 1.279, 95%CI 1.075-1.521; P=0.005), non-responsible vascular stenosis ( OR 2.518, 95%CI 1.145-5.536;P=0.022), and large artery atherosclerotic stroke ( OR 2.010, 95%CI 1.009-4.003; P=0.047) w ere the independent risk factors for unfavorable outcome in minor ischemic stroke. Conclusions The early poor outcome of minor ischemic stroke is closely associated w ith age, heart diseases, baseline NIHSS score, limb movement disorder, ataxia, early neurological deterioration, infarct diameter, non-responsible vascular stenosis, and large artery atherosclerotic stroke. The relevant examinations need to be improved early, the etiologic subtype should be identified, and the correct clinical treatment should be guided.

Treatments for primary aneurysmal bone cysts of the cervical spine: experience of 14 cases / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Aneurysmal bone cyst (ABC) is a benign lesion with the potential to be locally aggressive. The optimal treatment of cervical spine lesions remains controversial. This retrospective study was designed to evaluate the different treatments for primary ABCs of the cervical spine.</p><p><b>METHODS</b>This series included eight men and six women diagnosed between 2002 and 2012. A retrospective review of the hospital charts, operating room reports, office charts, and radiographs was performed. The data collected included patient age, sex, radiological features, pathology, treatment methods, outcomes, and complications from biopsies and treatments. The mean age at diagnosis was 17.5 years old with a range of 6-35 years. All patients had experienced local pain for a mean of 7.3 months (range, 0.5-18.0 months), and three patients had neurological deficits (one with radiculopathy and two with myelopathy). The Frankel classification before treatment was E in 12 cases, D in one case, and C in one case.</p><p><b>RESULTS</b>Four patients received radiotherapy alone. Ten patients underwent surgery, including five total spondylectomies, two local resections, and three curettages. Three patients received preoperative selective arterial embolization, and four received adjuvant radiotherapy. The mean follow-up time was 44.5 months (range 12-96 months), and no recurrence was identified. Three patients with neurological deficits achieved complete recovery, as noted at the final follow-up examination. One patient received radiotherapy without appropriate immobilization as prescribed and developed C1-C2 subluxation with severe spinal cord compression but without myelopathy. He refused further treatment.</p><p><b>CONCLUSIONS</b>The results can be achieved by different treatments (surgical resection/curettage, selective arterial embolization, and radiotherapy) for ABC of the cervical spine. Reconstruction of stability is also important for the treatment of cervical ABC.</p>

Analysis of genotype resistance mutations sites among 123 antiretroviral-therapy failure in HIV/AIDS patients in Yunnan province, China / 中华检验医学杂志

Objective To analyze the prevalence and diversity of genotype resistant mutations in 123 HIV/AIDS patients experiencing failure of high antiretroviral therapy (HAART) in Yunnan province.Methods A cross-sectional survey was conducted among 151 HIV/AIDS patients experiencing failure of antiretroviral therapy form January 2011 to January 2012 in Yunnan province.The HIV-1 pol gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR),the sequences were then submitted to the Stanford University HIV drug resistance database to analyze the prevalence of resistant mutations.The resistant mutations were statistically analyzed by gender,ethnic groups,transmission route and subtype,respectively.The chi-square or fisher's exact test was used for statistical test.Results Of the 151 cases,123 plasma samples were amplified successfully for protease PR (codon 1-99) and reverse transcriptase RT (codon 1-272) fragments.The most common mutation was M184 (72.4％),followed by the mutation at position K103 (47.2％),T215 (26.0％),D67 (15.4％),G190 (34.1％),Y181 (29.3％),K101 (17.1％).The frequency of mutations at position V75,A62 and M230 was higher in male population than that in female population (x2 =7.001,6.975,5.446,P ＜ 0.05).The frequency of variants at position Tl215,K70 and T69 was higher in the Han population than in the other ethnic population(x2 =5.290,4.060,3.860,P＜ 0.05).It was interesting that the variant M41L was rare in the other ethnic groups.The significant difference existed at various transmission routes.Frequencies of variants at position T215 and T69 were significantly higher among people infected HIV-I through sexual contact than the intravenous drug users (x2 =10.431,7.952,P ＜ 0.05).Frequencies of variants at position G190 were significantly higher among the intravenous drug users than the population infected HIV-1 through sexual contact(x2 =6.669,P ＜ 0.05),but the variant M230L never occurred in intravenous drug users.The RT mutations V75,T69,M230 were more frequently occurred in patients infected with CRF01_AE than in patients with subtype B (P＜ 0.05).The mutation L74 was never seen in patients infected with CRFOI_AE (P ＜ 0.05).Conclusions The HIV/AIDS patients with failure of high antiretroviral therapy (HAART) were attributed to HIV-1 genotype resistance mutations.The mutation sites among the HAART failure patients from the regions of Dehong,Gejiu,Wenshan and Yuxi were significant difference accordance among the gender,ethnicith,transmission route and subtype,respectively.

Imaging findings of solitary fibrous tumors / 中华放射学杂志

ObjectiveTo investigate the imaging characteristics of solitary fibrous tumor(SFT).MethodsThis study included 11 cases with SFT proved by pathological results.The imaging manifestations were retrospectively reviewed and analyzed in comparison with surgical and pathological results. Among them,8 patients underwent CT plain scan (1/8) or enhanced scan (7/8),4 patients underwent MR plain scan (2/4) or enhanced scan (2/4),and only 1 patient underwent both CT and MR scan.Results( 1 )SFT were located in the thoracic cavity(2/11 ),abdominal and pelvis(5/11 ),and somatic soft tissues (4/11 ).The average tumor size was 11.8 cm ( 2.5 to 23.0 cm).Among them,4 tumors were round or ellipse,and 7 tumors were irregular.Eight tumors had well-defined contours,and the others showed illdefined contours.(2)On CT scan,all SFTs showed inhomogeneous density with low density areas.Calcification was seen in I case,and hemorrhagic foci were detected in 2 cases.(3)On MR scan,all SFTs showed intermediate signal intensity on T1 WI.Three tumors were slightly hyperintense and the other was hypointense on T2WI.All of them were rich of vascular signal voids.Three tumors,including 2 tumors with scattered long T1 and T2 signal and 1 tumor in the liver with hyperintense haemorrhage,displayed inhomogeneous mixed signal.One tumor in the orbit showed homogeneous signal.(4)On enhanced scan,9 tumors showed irregular enhancement with multiple circuitous vessels in the arterial phase,and continuous or progressive enhancement with patch non-enhanced areas in the venous phase.( 5 ) Histologically,SFTs were composed of juxtaposed hyper- and hypo-cellular spindle cells,dense collagenous stromas and numerous thin-walled blood vessels with a staghorn configuration.Conclusion The possibility of SFT should be considered when a single soft tissue mass with sharp border,inhomogeneous density is detected,especially with inhomogeneous enhancement maintaining in the venous phase.

Investigation of pol gene variation of HIV-1 epidemic strains after treatment with HARRT at Dehong prefecture and Kunming in Yunnan province / 中华检验医学杂志

Objective To investigate the variations in the pol region of HIV-1 strain in treatment failed patients in Yunnan province's Dehong prefecture and Kunming. Methods Blood samples were collected from 139 patients who experienced treatment failure ( HAART treatment ＞ 1 years and HIV-1 RNA Viral load ＞ 1 000 copies/ml). HIV-1 RNA was extracted from plasma, and nested-PCR was performed for amplification of PR and RT genes on the HIV-1 pol region. The PCR products were then sequenced and submitted to Stanford HIV Drug Resistance Database for comparison. The evolution tree was built up with MEGA 4. 1 system, combined with patients' demographics. Results The most prevalent mutation in Kunming patients were T215F/N/Y/I, M41L/M, and T69G/N/I/S/A/D, the mutation rates were 39%(24/62), 27% (17/62) and 27% (17/62) , respectively, which were higher than the corresponding mutations in the Dehong prefecture [16% ( 11/69), 13% (9/69) and 9% (6/69)]. The rate differences were statistically significant ( x2 = 8.646, 4.242 and 7. 909, all P ＜ 0.05 ). The most common HIV-1 pol region subtype in the Dehong patients were CRF01_AE subtype (32%, 22/69), followed by C subtype (25% ,17/69), and B subtype ( 19%, 13/69). Major subtypes in Kunming patients were 08_BC (60%,37/62 ), CRF01_AE subtype(21% , 13/62 ) and 07_BC ( 15% ,9/62). Conclusions Partial differences of the point mutations of the HIV-1 strain pol region and frequency of their occurrences exist among Dehong and Kunming patients, HIV-1 strains in Dehong prefecture for the NNRTIs mutations at the T215 Y/N/T, M41L and T69G/N/I/S/A/D are significantly higher than those in Kunming. Six isoforms are found respectively:CRF01_AE, B, C, BC, 08_BC and 07_BC from the epidemic strains of HIV-1 pol region subtype in Dehong and Kunming areas.

Vertical Dissemination of Escherichia coli and Klebsiella pneumoniae Isolates Producing Extended-spectrum Beta-lactamases in Hospital / 中华医院感染学杂志

OBJECTIVE To investigate the epidemic situation of vertical dissemination of the Escherichia coli(ECO) and Klebsiella pneumoniae(KPN) isolates producing extended-spectrum beta-lactamases in the hospital.METHODS The fingerprints of the isolates were obtained by pulsed-field-gel-electrophoresis(PFGE),and were analyzed with software Quantity One.RESULTS The similarity of 10 isolates and 7 isolates among the 21 ECO(isolates) from ICU was more than 90%,and 100%,respectively;the similarity of 3 KPN isolates was 100%.The similarity of 9 isolates among the 20 ECO(isolates) was more than 90% and the similarity of 4 isolates among the 6 KPN isolates was more than 90% in the neurosurgery ward.The similar coefficients of 3 isolates and 2(isolates)(among) the 10 ECO isolates from the ward for cadre were more than 90% and 100%,(respectively.) The similar(coefficients) of 2 isolates among the 7 ECO isolates from the gastroenterology ward and 2(isolates)(among) the 18 ECO isolates from the respiratory ward were more than 90%.The isolates whose similarity was more than 90% were also found in other wards.CONCLUSIONS There are vertical disseminations of single clone of ESBL-producing organisms in several wards,especially in the ICU.It is necessary to strengthen the management of(infection)-control.

Monoclonal antibodies against human telomerase reverse transcriptase: preparation, characterization, and application / 中华病理学杂志

<p><b>OBJECTIVE</b>To develop monoclonal antibodies against the catalytic subunit of human telomerase hTERT for its expression detection of human tumors.</p><p><b>METHODS</b>A dominant epitope in hTERT (peptide hTERT(9))was automatically synthesized based on Fmoc method, and was used to immunize BALB/c mice. Hybridomas were generated and screened by ELISA for specific monoclonal antibodies, and the characterization of which were performed by Western blotting and immunohistochemical staining.</p><p><b>RESULTS</b>Antigenic peptide hTERT(9) was synthesized and confirmed by MALDI-TOF-MS and HPLC analysis. Three hybridoma cell lines secreting anti-hTERT(9) antibodies designated as H4, G8 and A11 were established after primary screening and consequent three rounds of limited dilution. Both of H4 and G8 were IgM, while A11 was IgG1 in isotyping. The competitive assay showed that the antibodies were hTERT(9) specific, and the affinity of G8 was stronger than that of H4 and A11 assayed by affinity ranking. However, in Western blotting, both of H4 and G8 stained an about 123 000 protein band with HeLa and 293 cell extracts but not with normal 2BS cells. Besides, positive staining presented in the nucleus of HeLa, while 2BS was non-reactive immunohistochemically. The sections from paraffin-embedded blocks of 127 cases of human cancer, 40 of precancerous and 19 of benign tumors were in situ stained by G8 antibody, the results showed that the human cancer tissues were 80.31% (102/127) positive in specific nuclear reaction, on the contrary, only a minority of precancerous lesions present weak positive (17.5%, 7/40), and negative in benign tumors (0/19).</p><p><b>CONCLUSIONS</b>The monoclonal antibodies developed against synthetic peptide were hTERT-specific and could recognize both the native and the denatured form. Thus their use in immunoblotting or immunohistochemistry for detecting the telomerase hTERT expression of cancer cell and tissues was promising.</p>

Single domain antibody to human telomerase catalytic subunit: preparation and characterization / 中华病理学杂志

<p><b>OBJECTIVE</b>To develop a recombinant single domain antibody against hTERT, human telomerase catalytic subunit.</p><p><b>METHODS</b>A previously prepared His-tagged hTERT fusion protein was used as the antigen, and the variable regions in heavy chain (VH) of immunized mice were RT-PCR amplified and cloned into the pCANTAB 5E, a phagemid vector. By transfection, the display library of mouse VH was developed. The candidate clones were selected by affinity panning, and soluble VH were obtained after expression in E. coli, HB2151. The resultant single VH antibodies were characterized on their binding potentials by western blotting.</p><p><b>RESULTS</b>An about 350 bp VH fragment was amplified from spleen cells of mice immunized by His-tagged hTERT and expressed by phage displayed as VH library. The size of the library was 8 x 10(4). After three rounds of affinity panning, 4 independent clones were chosen and consequently expressed as soluble single domain antibodies (Mr = 16 000). In Western blot analysis, the single domain antibody from 2 of 4 clones proved to react with the His-tagged hTERT fusion protein (Mr = 167 000) without dependence of His-tags and also detect the native hTERT (Mr = 127 000) extracted from the human HeLa cancer cell line. DNA sequencing showed both of the single domain antibodies were encoded by the heavy chain variable region of the mouse.</p><p><b>CONCLUSIONS</b>The single domain antibodies developed were hTERT recognizable and hTERT specific, thus providing a basis for application of recombinant single domain antibody in inhibition of telomerase activity and anticancer therapy.</p>

The clinico-pathological characteristics of nodular goiter with lymphocytes infiltration / 中国普通外科杂志

Objective To investigate the clinico-pathological characteristics of nodular goiter (NG) with lymphocytes infiltration and its relationship with Hashimoto′s disease. Methods Clinical and histologic data were collected and reviewed for 1121 cases of nodular goiter and 55 cases of thyroid adenoma, among which 83 cases had lymphocytes infiltration. These 83 cases of NG with lymphocytes infiltration were observed histologically in detail, followed up and assessed for the correlation of thyroid function to histologic findings. Results The overall incidence of lymphocytic infiltration in non-toxic nodular goiter was 7.4% (83/1121). Most of them were women of middle age. All had lymphocytes infiltration, follicule atrophy and oxiphilic epithelia in the background of nodular goiter. Seventy-six percent underwent cystic degeneration or had fibrous scar. Nineteen percent with lymphocytes infiltration in NG developed post-operative hypothyroidism. Six cases (7%) had high levels of thyroid auto-antibodies. None of the 55 cases of thyroid adenoma had overt lymphocytes infiltration. Conclusion Nodular goiter with lymphocytes infiltration and Hashimoto′s disease shares similar morphology and clinical presentation in some degree. It seems that NG with lymphocytes infiltration is a kind of inflammatory hyperplasia relating to autoimmunity and perhaps the beginning of some cases of Hashimoto′s disease.