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Background Parkinson's disease (PD) , as one of the most common neurodegenerative diseases, has become a global medical problem due to the obvious adverse reaction of drug treatment and the reduced efficacy of long-term use. Guasha is one of the widely used non-drug therapies of traditional Chinese medicine (TCM) with unique advantages in the treatment of nervous system diseases. At present, there are few studies on the treatment of idiopathic PD with Guasha combined with drug therapy. Objective To explore the short-term clinical effect of Guasha combined with drug therapy for idiopathic PD. Methods Sixteen patients with idiopathic PD in the early and middle stages selected by the purposive sampling method from March 2021 to September 2021 in outpatients of Nanjing Hospital of Chinese Medicine and Jiangsu Province Hospital were selected as the observation group, and another 16 patients with idiopathic PD were selected as the control group according to the principle of matching gender, age, course of disease and Hoehn-Yahr stage. The observation group was treated with Guasha combined with western medicine orally for 4 weeks as a course of treatment; after 3 courses of treatment, Guasha was stopped and western medicine orally continued for 1 course of treatment as follow-up. The control group was treated with simple western medicine orally for 4 weeks as a course of treatment, and the last one of 4 courses of treatment was recorded as follow-up. After 3 months of treatment and 1 month of follow-up, the Movement Disorder Society-Unified Parkinson's Disease Rating ScaleⅢ (MDS-UPDRSⅢ) score, Non-motor Symptom Score (NMSS) and clinical efficacy were observed. The levels of serum interleukin-1β (IL-1β) and nuclear transcription factor κB (NF-κB) were observed after 3 months of treatment. Results After 3 months of treatment, the scores of MDS-UPDRS Ⅲ and NMSS, and the levels of serum IL-1β and NF-κB in two groups were lower than those before treatment (P

For comprehensive utilization of coal gangue and iron ore tailings, XRD, FE-SEM and EDX were used to analyze hydration products and microstructure of autoclaved aerated concrete (AAC) mainly from coal gangue and iron ore tailings. Furthermore, it was studied that the influence of raw materials and the optimal thermal activation temperature of coal gangue to physical and mechanical prosperities. The results show that 600 °C is the optimal calcination temperature AAC with bulk density of 608 kg/m³ and strength of 3.64 MPa, which can reach the requirements of A3.5, B06 level of AAC product regulated by "autoclaved aerated concrete block" GB 11968-2006. There exists ettringite before autoclaved and the main hydration products are tobermorite, C-S-H gel and hibschite, which is globular and botryoidalis. [ABSTRACT FROM AUTHOR]

Objective: To investigate hippocampal development deviation and its association with cognition in patients with major psychiatric disorders (MPDs), including schizophrenia, bipolar disorder and major depressive disorder., Methods: The T1-weighted MRI data of 174 first-episode drug-naïve schizophrenia (FES) atients, 169 bipolar disorder (BD) patients, 184 major depressive disorder (MDD) patients, and 321 healthy controls were collected and their hippocampal volume was extracted after preprocessing with Freesurfer 5.3. A normative neurodevelopment model was applied to calculate the hippocampal deviation scores. Data on cognitive functions, including visual memory, attention, spatial working memory, were collected. Comparison by different sexes was made to identify difference between the hippocampal development deviation scores of the control group and those of the disease groups. We also investigated the moderating effect of age on the deviation score and explored the association between the deviation score and cognitive function., Results: The hippocampal development deviation scores of patients with MPDs were significantly lower than those of the healthy controls (false discovery rate [FDR]- P <0.05). Analysis of the moderating effect of age revealed lower deviation scores in young patients (<[25.83-28.56] yr.) and higher deviation scores in old patients (>[35.87-54.35] yr.) in comparison with those of the healthy controls. The right hippocampal deviation scores in male FES patients were positively correlated with the number of errors for tasks concerning spatial working memory ( r =0.32, FDR- P =0.04)., Conclusion: Our findings suggest abnormal hippocampal development in MPDs patients and its different distribution in MPDs patients of different age groups. The hippocampal development deviation score may provide a new perspective for further understanding of etiology in MPDs., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Objective: To investigate frequency-specific alterations of spontaneous brain activity in first-episode drug-naïve schizophrenia (SZ) patients and the associations with clinical symptoms., Methods: We collected the resting-state functional MRI (rs-fMRI) data from 84 first-episode drug-naïve SZ patients and 94 healthy controls (HCs) and calculated the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) of four frequency bands, including slow-2, slow-3, slow-4, and slow-5. Two-sample t -tests were used to evaluate the intergroup differences in ALFF and ReHo, while partial correlation analyses were conducted to explore the associations between abnormal ALFF and ReHo and the severity of clinical symptoms in the SZ group., Results: Compared with HCs, the SZ group showed reduced ALFF in superior cerebellum and cerebellar vermis across slow-2, slow-3, and slow-4 bands, while increased ALFF was found in left superior temporal gyrus, middle temporal gyrus, and superior temporal pole at slow-4 band. Moreover, reduced ReHo was observed in the right precentral and postcentral gyri at slow-3 band in the SZ group. Additionally, the ALFF of left superior temporal gyrus, middle temporal gyrus, and superior temporal pole in slow-4 band showed a trend of positive correlation with the excited factor score of Positive and Negative Syndrome Scale (PANSS) in the SZ group., Conclusion: Our results suggest that local alterations of spontaneous brain activity were frequency-specific in first-episode drug-naïve SZ patients., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Objective: To investigate the clinical characteristics of the patients with chronic myeloid leukemia (CML) discontinued tyrosine kinase inhibitors (TKI) therapy and the outcome of the patients., Methods: 35 cases of CML patients experienced initiative discontinuation of TKI therapy in our hospital from June 1st 2015 to December 31th 2019 were retrospectively analyzed. The TFR of the patients and the factors affecting it were analyzed., Results: The median duration of TKI administration was 72 (range 35-173) months in the 35 patients. Among these patients, 8 had experienced TKI dose reduction or suspension. All the enrolled patients have achieved at least MMR. The median time for these patients achieving MMR was 15 (range 3-75) months after administration of TKI, and for MMR maintenance before TKI suspension was 55 (range 13-164) months. After TKI withdrawal the median follow up time was 20.3 (range 3-57.9) months, 22 out of 35 patients kept TFR, among them, 2 （5.71%） patients restarted TKI after 12 month suspension, and maintained MMR during suspension. 13 （37.1%）patients lost MMR, among them, 9 patients restarted TKI treatment, and 5 of them achieved MR4.0 after the median duration of 3(2-5) month. No patients were found to have disease progression. The estimated TFR rate was 57.8% and 51.8% at 12 and 24 months after discontinuation, respectively. Other clinical characteristic related to relapse were also analyzed, including the cumulative TKI administration duration, cumulative MMR duration, time to achieve MMR, median age at diagnosis, risk stratification by Sokal score, TKI dose reduction and discontinuation history, and second-generation TKI administration before stopping TKI, however, no statistical difference was found., Conclusion: TKI discontinuation is practical for CML patients in our center.

Objective: To investigate the clinical characteristics, laboratorial and bone marrow pathological features of primary thrombocytopenia (ET) patients with different mutations of CALR, JAK2 and MPL genes., Methods: The chinical data of 120 cases of ET in Jiangsu provincial people's hospital/ The First Affiliated Hospital of Nanjing Medical University from January 2015 to December 2017 were collected and analyzed, including 76 cases with JAK2 gene mutation, 40 cases with CALR gene mutation, 2 cases with MPL gene mutations, 2 cases without gene mutation., Results: Among the ET patients, compared with the JAK2 gene mutation, CALR gene mutation showed statistically significant deareament of white blood cells and hemoglobin (P=0.001, P=0.01) and the male platelets in CALR group showed significant increament (P=0.04). Fourthermore, the average number of megakaryocytes and its cluster numbers in each hight power field of vision showed statistically significant decreament in CALR group as compared with JAK2 group (P=0.001, P=0.001), and thrombotic events in CALR group were signicantly lower than those in JAK2 group (7.5% vs 18.4%) (P=0.03)., Conclusion: Mutations of CALR, JAK2 have different clinical characteristics and blood pathological changes of Chinese ET patients, and their clinical significance is worth to explore.

Objective: To analyze the clinical and laboratory features of acute myeloid leukemia (AML) with cuplike nuclei morphology., Methods: One hundred and seventy patients diagnosed with AML (M1andM2) between December 2009 and December 2016 were included in the study. Bone marrow smears were prepared for morphologic alanalysis, the immunophenotype was analyzed by flow cytometry and the RHG-banding was for conventional cytogenetic assay (CCA) ,gene mutation was detected by sequencing., Results: Among the 170 AMLpatients, 67 were diagnosed as M1 and 103 patients was diagnosed as M2, 43 patients(25.3%) defined as cuplike nuclei-positive, among them 38patients (88.4%) were M1 while only 5 patients (11.6%) were with M2(P<0.01). No significant value about sex(P> 0.05) between cuplike nuclei-positive and -negative group, while older patients were found in cuplike nuclei-positive group (P<0.05). Higher peroxydas (POX) ratio (P<0.05) and integration (P<0.05) were found in cuplike nuclei- positive group. Furthermore, the patients with cuplike nuclei-positive lack the expressions of CD34 (P<0.01) and HLA-DR(P<0.01) while no other immunophenotype markers were found. Among the 152 patients (89.4%) for genetic analysis ,83.8% karyotype of the cuplike nuclei-positive group were normal while only 54.8 of negative group was normal by CCA. Molecular biology analysis showed that the patients in cuplike nuclei-positive group have significantly highe rNMP1 (P<0.01) and FLT3(P<0.01) mutations as compared with the negative group. Furthermore, the relationship of the ratio o fcuplike nuclei and the type of gene mutations were investigated, and no significant associations were found. However, it was found that the patients with FLT3 mutation displayed more biological nuclear invagination than the patients with NPM1 mutations (P<0/01)., Conclusion: AML patients with positive cuplike nuclei have characteristic morphological changes, typical immunophenotype with HLA-DR- and CD34 - , normal karyotype accompanied by NPM1 and FLT3 mutations.

Objective: The past studies found that the treatment of chronic myeloid leukemia (CML) with imatinib can induce the macrocytic anemia, moreover the incidence of anemia increases along with enhancement of imatinib concentration. This study was aimed to evaluate the potential relation of erythrocyte mean corpuscular volume (MCV) increase after the treatment with tyrosine kinase inhibitors (TKI) with the therapeutic response in patients with CML-chronic phase (CML-CP)., Methods: The clinical and hematologic data including MCV, molecular and cytogenetic response of 119 patients with CML-CP were collected after treatment with TKIs, and the relation of MCV changes after treatment with the clinical characteristics and therapeutic efficacy for patients with CML-CP was analyzed., Results: The MCV in patients treated with TKIs for 12 months significantly increased as compared with that at initial diagnosis (P<0.05). The proportion of patients with increased MCV in group of complete cytogenetic response (CCyR) was significantly higher than that in group of non-CCyR (P<0.05). As compared with decreased MCV group, the patients in increased MCV group much more easily achieved CCyR after treatment for 6, 12 months (P<0.05, P<0.05) respectively, furthermore, much more easily maintained MMR (P<0.05)., Conclusion: The MCV as a parameter which is easily acquired may be a new marker for prodecting the therapeutic response of patients treated with TKIs.

Objective: To correlate the clinical features of patients with acute myeloid leukemia (AML) with mutations of FLT3-ITD, NPM1, CEBPA, c-KIT, DNMT3A and ND4 genes as well as chromosomal aberrations., Methods: Somatic mutations of aforementioned genes in 412 newly diagnosed AML patients were detected with PCR and direct sequencing. All patients were also subjected to R-banding chromosomal analysis. The results were correlated with the clinical features and prognosis of the patients., Results: The mutation rates of FLT3-ITD, NPM1, CEBPA, c-KIT, DNMT3A and ND4 were 9.0% (26/289), 19.1% (50/262), 18.9% (34/180), 3.4% (7/208), 6.6% (9/137) and 6.9% (4/58), respectively. Patients with poor prognosis based on genetic mutations had lower blood platelet count than those with intermediate and good prognosis (P=0.001 and P=0.001, respectively). None of the three groups attained median overall survival (OS) (P> 0.05). The complete remission (CR) was similar among the three groups (P> 0.05). For patients with different prognosis based on cytogenetic findings, white blood cell count in those with intermediate prognosis was higher than those with good and poor prognosis (P< 0.001 and P=0.004, respectively), while the blood platelet count of the intermediate group was higher than that of the group with good prognosis (P=0.018). No significant difference was found among the three groups in terms of hemoglobin level (P> 0.05). The group with poor prognosis has attained shorter OS compared with those with good and intermediate prognosis (P< 0.001 and P=0.003, respectively). However, the CR rate of the group with good prognosis was higher than that of the intermediate group (P=0.001). For the group with intermediate prognosis, presence of genetic mutations did not correlate with the clinic characteristics such as white blood cell count, blood platelet count, hemoglobin level, OS and CR rate (P> 0.05 for all comparisons)., Conclusion: Genetic mutations combined with cytogenetic analysis can facilitate the prognosis and personalized treatment for patients with AML.

Objective: Cytokine receptor-like factor 2(CRLF2) plays an important role in the development of normal B lymphocytes, which can mediate early B cell proliferation and survival. The aim of this study was to investigate the mutations of CRLF2 and its clinical significance in adult patients with acute lymphoblastic leukemia(ALL)., Methods: Exons of CRLF2 were amplified, then the DNA was purified and sequenced; the frequency, position, types and clinical significance of CRLF2 mutations were analyzed., Results: 6 types of genetic alterations in CRLF2 were found, among them the R186S prompted better prognosis, while L86I, F232F and W255C associated with poor prognosis., Conclusion: CRLF2 mutations may play an important role in the development and progressions of adult patients with ALL, and these genetic abnormalities may associate with clinical outcome.

Objective: To investigate the accuracy and consistency of the detection of BCR-ABL tyrosine kinase domain point mutation among different laboratories., Methods: Every one of 6 laboratories prepared 10 cDNA samples from tyrosine kinase inhibitors resistant BCR-ABL (P210 or P190) positive patients'bone marrow or peripheral blood. Each cDNA sample was divided into 6 aliquots and delivered to the laboratories. All 6 laboratories tested BCR-ABL point mutations of 60 samples according to their own protocols. Peking University People's Hospital analyzed the comparison results based on both the reports and sequencing chromatogram from all laboratories., Results: All laboratories reported the same nucleotide and corresponding amino acid mutations in 37 samples (61.7%）. Of 60 samples, 53 had confirmed mutation types, and a total of 23 types were included; 1 had no mutation; mutation types of 6 samples could not be determined because of the big differences among chromatograms from different laboratories. Low percentages of mutants were significantly related to results inconsistency (P=0.008). Inconsistent result of one sample was caused by the unique chromatogram of the mutant L248V, and one by the non-coverage amplification of PCR product from different laboratories. Amplification was failed in 3 samples. Testing or sequencing mistakes occurred in 7 samples. The differences in the mutant percentages among laboratories were less than 20% in the 80.6% of samples with confirmed results. Low internal control gene copies (ABL<10 000) were significantly related to both failed amplification and big differences among chromatograms from different laboratories (P=0.005 and <0.001, respectively)., Conclusion: Problems in the clinical routine detection of BCR-ABL point mutation could be exposed and improvement could be achieved by sample exchange and comparison. Low percentage of mutant is the main reason which causes the discrepancy of BCR-ABL point mutation results among different laboratories.

Objective: To investigate the expression of BAG3 gene in acue myeloid leukemia (AML) and its prognostic value., Methods: Real-time quantitative RT-PCR was used to detect the expression of BAG3 mRNA in 88 previously untreated AML patients. The corelation of BAG3 expression level with clinical characteristics and known prognostic markers of AML was analyzed., Results: In 88 patients with AML, the expression of BAG3 mRNA in NPMI mutated AML patients was obviously lower than that in NPMI unmutated patients (P = 0.018). The expression level of BAG3 mRNA did not related to clinical parameters, such as age, sex, FAB subtype, WBC count, extra-modullary presentation, and to prognostic factors including cytogenetics, FLT3-ITD, c-kit and CEBPα mutation status (P > 0.05). The expression level of BAG3 had no obvious effect on complete remission (CR) of patients in first treatment. The expression level of BAG3 in non-M3 patients was higher than that in relapsed patients (P = 0.036). The expression level of BAG3 had no effect on overall survival (OS) of patients., Conclusion: The expression level of BAG3 does not correlated with known-prognostic markers of AML, only the expression level of BAG3 in NPM1 mutated patients is lower than that in NPM1 unmutated patients. The expression level of BAG3 has no effect on OS of AML patients, the BAG3 can not be difined as a prognostic marker in AML.

Objective: To explore the mutational status of CALR, JAK2 and MPL genes in BCR-ABL negative myeloproliferative neoplasms (MPN) patients and the clinical features of MPN patients with these mutations., Methods: A total of 246 patients with a definite diagnosis of BCR-ABL negative MPN were enrolled from January 2009 to January 2014 into this study. Among them, there were 48 cases of polycythemia vera (PV) patients, 171 cases of essential thrombocythemia (ET) patients and 27 cases of primary myelofibrosis (PMF) patients. And CALR, JAK2 V617F, 12 exons of JAK2 and MPL W515L/K genes were amplified by PCR and sequenced directly. Clinical features were also analyzed in patients., Results: Among 246 cases of BCR-ABL-negative MPN patients, 52 cases (21.1%) had CALR mutation, 121 cases (49.2%) JAK2 V617F mutation, 0 case (0) 12 exons of JAK2 mutation, and 2 cases (0.8%) MPL W515L/K mutation, respectively. These mutations were found existing exclusively. In PV patients, the white blood cell and platelet counts in JAK2 V617F mutated group were higher than those in wild-type JAK2 V617F group, while the level of hemoglobin was higher in wild-type JAK2 V617F group (all P<0.05). In ET patients, the white blood cell count, the level of hemoglobin, the frequency of thromboembolic events and risk stratification in JAK2 V617F mutated group were higher than those in CALR mutated group (all P<0.05). In PMF patients, the level of hemoglobin in JAK2 V617F mutated group were significantly higher than those in CALR mutated group (P<0.05)., Conclusions: The proliferative level of bone marrow, risk of thromboembolic events and stratification are lower in CALR mutated patients than those in JAK2 V617F mutated patients. The pathogenic mechanism of mutated gene should be further investigated in future.

Objective: To evaluate the impact of Fc gamma receptor IIIa (FcγR IIIa) polymorphisms on the efficacy of rituximab (RTX) combined chemotherapy for patients with diffuse large B-cell lymphoma (DLBCL)., Methods: FcγRIIIa polymorphisms were analyzed by PCR in 122 patients and 100 healthy controls. All patients received 8(4-12) cycles of RTX combined chemotherapy., Results: 78(63.93%) patients with F/F, 5(4.10%) with V/V, and 39(31.97%) with V/F were identified, which were not different compared to controls. Patients with different FcγRIIIa genotypes did not have any difference in terms of gender, age, molecular subtypes, lactate dehydrogenase (LDH) or international prognostic index (IPI). The overall response rate (ORR) was 89.35% with a complete response (CR) of 80.33% and a partial response (PR) of 9.02%. The ORR was 83.33%, 100.00% and 100.00% in F/F, V/V and V/F, respectively. A higher response rate was observed in V/V and V/F as compared with F/F (P<0.05). With a median follow-up of 35 months (range: 12-62 months), 46(37.71%) patients had relapsed and 40 (32.79%) cases progressed and ended in death. The 3-year progress-free survival (PFS) rate was 41.03%, 100.00%, 100.00% in F/F, V/V and V/F, respectively. The 3-year overall survival (OS) rate was 48.72%, 100.00% and 100.00% in patients with three genotypes. The PFS and OS rate were significantly higher in V/V and V/F as compared with F/F (P<0.05)., Conclusion: FcγR III a polymorphisms could predict response and prognosis of RTX combined chemotherapy for patients with DLBCL.

Objective: To investigate the relationship of the mutational status of the ND4 gene and the clinical features of acute myelogenous leukemia (AML) patients with ND4 mutations., Methods: Using PCR combined with directly sequencing, we identified somatic mutations of ND4 in 121 primary AML patients to couple with their clinical features., Results: There were 58 male patients and 63 female patients (median age 49 years, 10-86 years). Eight of 121 patients (6.6%) with de novo AML were found harboring missense mutation of ND4 gene, including 3 patients with A131V (3/8, 37.5%), 2 patients with A404T (2/8, 25%), 1 patient with F149L (1/8, 12.5%), 1 patient with G242D (1/8, 12.5%) and 1 patient with Y409H (1/8, 12.5%), respectively. Patients with ND4 mutations were associated with good karyotype (P=0.049), regardless of gender, age, white blood cell, hemoglobin, platelet, blast cells of bone marrow or immunophenotype (P>0.05). There were no statistical significance in mutations of FLT3-ITD, NPM1, CEBPA, c-KIT and DNMT3A between patients with ND4 mutation and wild-type (wt) ND4 (P>0.05). The median overall survival of patients with ND4 mutations and wt ND4 were all not reached. The median relapse-free survival were not reached and 29(2-53) months, respectively (P>0.05). There was no significance in the ratio of CR and RR patients between wt ND4 and ND4 mutated groups (P>0.05)., Conclusion: It was concluded that novel ND4 mutations could be found in de novo AML patients, especially in patients with good karyotype. Thus, ND4 mutations might play an important role in AML prognosis. However, whether the mitochondria dysfunction contribute to leukemogenesis needs to be further investigated.

Objective: To validate the conversion factor (CF) for the conversion of BCR-ABL (P210) transcript levels to the international scale in chronic myeloid leukemia (CML)., Methods: In 2012, the international reference laboratory in Adelaide, Australia (IMVS) sent two batches of RNA samples, 30 samples per batch, to Peking University People's Hospital (PKUPH). By comparing BCRABL (P210) transcript levels reported by the two laboratories, CF of PKUPH was calculated and validated by IMVS. In 2013, PKUPH prepared the exchange samples for validation of CF of 9 hospitals who have calculated CFs before. The fresh BCR-ABL (P210) (+) cells were serially diluted by BCR-ABL (P210) (-) cells to prepare 22 kinds of samples with different BCR-ABL transcript levels, each kind had 10 parallel samples. Trizol reagent was added in each tube. Ten hospitals tested BCR-ABL transcript levels of one set of 22 samples. Agreement between BCR-ABL transcript levels of each laboratory and PKUPH was assessed by the Bland-Altman method., Results: PKUPH successfully validated its CF with bias 1.1 fold and 95% limits of agreement between -4.7 and 4.9 fold. Of 9 hospitals whose validation performed by sample exchanges with PKUPH, 6 hospitals successfully validated their CF with bias ≤±1.4 fold and 95% limits of agreement within ±6 fold., Conclusion: Validation of CF examined the stability of the detection of BCR-ABL (P210) transcript levels, which was necessary for the valid conversion of BCR-ABL (P210) transcript levels to the international scale in CML.

Objective: To investigate the chemical constituents from the twigs of Piper hancei., Methods: The chemical constituents were isolated and purified by means of chromatographic techniques including silica gel,Sephadex LH-20 and preparative RP-HPLC. Their structures were elucidated on the basis of physicochemical properties and spectral analysis., Results: Eight compounds were isolated and identified as 4-allylpyrocatechol(I), piperlonguminine(II), d-sesamin(Ill), beta-sitosterol (IV), pellitorine(V), piperolactam A(VI) and piperolactam D(VII), respectively., Conclusion: Compound I, III, VI and VII are isolated from Piper hancei for the first time.

Objective: To investigate SRSF2 mutations in patients with chronic myelomonocytic leukemia (CMML) and the clinical characteristics of patients with SRSF2 mutants., Methods: In this study, the frequency of SRSF2 mutation in a cohort of 20 patients with CMML was detected by polymerase chain reaction (PCR) followed by direct sequencing to couple with their clinical features., Results: Of 20 patients, 4 patients were found harboring SRSF2 mutations, including 2 P95L, 1 P95H and 1 P95R point mutations. There were no significantly statistical differences in terms of their clinical characteristics between mutant and wild type group., Conclusion: SRSF2 mutation was not frequently occurred in CMML patients and might associated with poor prognosis. It might be a practically diagnostic maker and therapeutic target in CMML.

This study was aimed to investigate the characteristics and clinical significance of NOTCH1 mutation in adult T-cell acute lymphoblastic leukemia (T-ALL). Exon 26/N-terminal region of the heterodimerization domain (HD-N) , exon 27/ C-terminal region of the heterodimerization domain (HD-C) , exon 28 and exon 34/ proline-glutamic acid-serine-threonine (PEST) domain of the NOTCH1 gene were amplified, cloned and sequenced in 42 adult patients with T-ALL to identify the frequency, position and type of NOTCH1 mutation, their correlations with laboratorial and clinical parameters, as well as their relevant prognostic significance. The results showed that the frequency of NOTCH1 mutation in this cohort of adult patients was 66.7% (28/42); A total of 45 types of NOTCH1 mutations were identified in present study, most of them were in HD-N (48.9%, 22/45) and PEST (40.0%, 18/45) domains. Mutation in amino acid 1575 (L1575P) was the top one type of mutation in HD-N (25.0%, 7/28), and amino acid 2443 was the most common mutation position in PEST domain (14.3%, 4/28). In newly diagnosed patients, white blood cell (WBC) >10×10(9)/L and blasts in bone marrow > 50% were predominant in patients with NOTCH1 mutation (91.7% vs 54.5%, P = 0.021 and 95.8% vs 57.1%, P = 0.006 respectively). Immunophenotyping analysis indicated that patients with CD10 positive were more in NOTCH1 mutation group than wild-type group (51.9% vs 0%, P = 0.006), whereas patients with CD15 and CD11b positive were less in NOTCH1 mutation group (5.3% vs 42.9%, P = 0.047 and 0% vs 57.1%, P = 0.002 respectively). It is concluded that NOTCH1 mutation in adult T-ALL has different characteristics and clinical significance from pediatric patients, and the difference between Chinese patients and patients in Western countries is also indicated.

Objective: To evaluate cyto- and molecular genetic characteristics of adult patients with acute lymphoblastic leukemia (ALL) and its prognostic significance., Methods: Two hundred and seventeen adult patients with ALL were analyzed for cyto- and molecular genetic characteristics with combined conventional cytogenetics, fluorescence in situ hybridization (FISH), real-time quantitative PCR (qPCR) and nested PCR. Significance of genetic findings for prognosis was evaluated., Results: t(9;22)(q34;q11)/BCR-ABL has been the most frequent abnormality found in the cohort (56.3%). And 22.4% of cases with BCR-ABL detected by FISH was negative by cytogenetic analysis. Ratio of patients in high-risk group increased with age; Patients with B-ALL had a higher risk group than the average-risk group (98.40% vs. 65.70%, P=0.000). The overall survival (OS) rates at 3-month (67.30% vs. 85.10%, P=0.042), 6-month (55.1% vs. 80.4%, P=0.008), 12-month (34.0% vs. 59.1%, P=0.017) and 24-month (13.0% vs. 36.6%, P=0.010) were lower in high-risk group than in average-risk group, with medium OS time (11 months, 95% CI 8.0-13.9) being significantly shorter compared with the average-risk group (19 months, 95%CI 10.8-27.1)., Conclusion: Adult patients with ALL have unique cyto- and molecular genetic characteristics, which has important value for prognosis and guiding treatment. Moreover, combined cytogenetic and molecular genetic techniques can precisely define sub-groups of ALL patients.

Objective: To investigate the comparability of bcr-abl (P210) transcript levels detected in different hospitals., Methods: Ten hospitals in China took part in the four times of sample exchange and comparisons from April, 2010 to August, 2011. The exchange samples were prepared by Peking University People's Hospital. Firstly, the BCR-ABL (P210)(+) cells from a newly diagnosed chronic myeloid leukemia patient were 10-fold serially diluted by BCR-ABL (P210)(-) cells and they covered 4 magnitudes. Then, TRIzol reagents were thoroughly mixed with cells in each tube. Every 12 samples (three samples per magnitude) were sent to the other 9 hospitals. The cell number of each sample was 8×10(6). The detection of bcr-abl transcript levels by real-time quantitative PCR were performed in every hospital according to their own protocols. Conversion factors (CF) were calculated using regression equation., Results: Differences in bcr-abl transcript levels did exist among results of 10 hospitals in each comparison. In general, the results of the most of hospitals were in line with the dilutions of cells. CF of every hospital fluctuated. Three hospitals had relatively stable CF, and their ranges were 2.8 - 5.2, 1.2 - 2.8 and 2.2 - 6.8, respectively; two hospitals had unstable CF with ranges 0.76 - 7.0 and 2.1 - 18.7; three hospitals couldn't be calculated CF one or two times because of the significant deviation of the results from the actually bcr-abl transcript levels, and their ranges of CF which could be calculated were 1.9 - 19.2, 3.6 - 7.6 and 0.18 - 14.7; One hospital only had two CF (3.3 and 5.0) because of the replacement of an important reagent during the period of comparisons., Conclusions: Comparability of bcr-abl (P210) transcript levels between different hospitals could be achieved through CF which acquired by sample exchange and comparison. The stable and reliable detection system is the premise to acquire correct CF.

Objective: To investigate immunoglobulin (Ig) and T cell receptor (TCR) gene rearrangements in bone marrow or peripheral blood of patients with non-Hodgkin's lymphoma (NHL), and to explore the potential clinical significance., Methods: The Ig/TCR gene rearrangements in bone marrow or peripheral blood of 139 NHL patients were analyzed by using BIOMED-2 multiple primers system and Multiplex PCR assay., Results: Ig clonality was detected in 85.4% (70/82) of chronic lymphocytic leukemia (CLL), including 46.3% (38/82) IgH rearrangement, 62.2% (51/82) IgK rearrangement and 1.2% (1/82) IgL rearrangement, and in 39.4% (13/33) of other categories of B-lineage NHL (B-NHL), including 33.3% (11/33) IgH and 39.4% (13/33) IgK rearrangements. TCR clonality was detected in 50.0% (12/24) of all definite T-lineage NHL (T-NHL), including 8.3% (2/24) TCRB and 45.8% (11/24) TCRG, no TCRD was detected. The detection rate of gene rearrangements of NHL diversed in different clinical stages \[36.4% in early stage (Ann Arbor stage I and II) and 45.6% in late stage (III and IV)\] and in different degrees of malignancy (40.0% indolent NHL and 45.6% aggressive NHL), but no obvious statistical significance was obtained (P > 0.05). The detection rate of bone marrow invasions of NHL (except CLL) with examinations of bone marrow smear under the microscope was 12.3% (7/57), much lower than the clonality testing (43.9%, 25/57) (P < 0.05). Sensitivity test showed that the sensitivity of malignant clonality testing by multiplex PCR was 3.12% - 6.25%., Conclusions: The detection rate of gene rearrangements diverses in different clinical stages and degrees of malignancy of NHL, but the correlation has not been proved in this research. The sensitivity of multiplex PCR-based clonality testing is enhanced with the combination of BIOMED-2 primers system. It is more sensitive than the morphological examinations of bone marrow smear in detecting bone marrow invasions, and may provide a powerful strategy in the routine diagnosis and assessment after treatment.

This study was aimed to investigate the expression level of murine double minute 4 (MDM4) mRNA in chronic lymphocytic leukemia (CLL) and its prognostic value in CLL. By means of β-actin as internal reference, the real-time quantitative RT-PCR was set up. The expression of MDM4 mRNA in 66 CLL patients was measured by fluorescence dye SYBR Green I. The dispersion of MDM4 expression ratio of groups with different prognostic factors was described by using Mann-Whitney U test. The results showed that the median MDM4 mRNA expression level was 0.037098 (0.088245-0.014875) in CLL patients. The expression level of MDM4 mRNA was significantly higher in patients with P53 gene deletion than that in patients without P53 gene deletion (0.13167 vs 0.030927) (p < 0.001), and also significantly higher in patients with P53 mutation than that in patients without P53 mutation (0.13167 vs 0.03077) (p < 0.001). MDM4 expression was also associated with Binet stages (p = 0.044) and ATM gene deletion (p = 0.046), but was not associated with LDH (p = 0.216), β(2)-MG (p = 0.314), TK1 (p = 0.300), ZAP-70 (p = 0.559), CD38 (p = 0.513) and IgVH mutation status (p = 0.333). It is concluded that the expression level of MDM4 is significantly higher in patients with P53 deletion or mutation. MDM4 expression is significantly associated with Binet stages and ATM gene deletion. MDM4 may be an important prognostic factor in CLL.

Objective: To explore the cytogenetic features of mantle cell lymphoma (MCL)., Methods: Bone marrow cells from 18 MCL patients with bone marrow invasion were cultured for 24 hours, then routine karyotype analysis was performed with R-banding technique. Interphase fluorescence in situ hybridization (FISH) and a panel of 5 probes, including CCND1/IgH, CEP12, D13S319, p53 gene and ATM gene, were used to investigate the cytogenetic features of the samples., Results: Chromosome aberrations were found in 9 (64.3%, 9/14) patients by conventional cytogenetics (CC), 8(57.1%, 8/14) patients had the aberration of t(11; 14), 6(42.9%, 6/14) had complex aberrant karyotypes, of which 2 (14.3%, 2/14) had highly complex aberrant karyotypes. A total of 28 abnormalities were detected, among them 19 (67.9%) were structural abnormalities, the other 9 (32.1%) were numerical aberrations. The aberration of t(11; 14) was found in all 18 (100%) patients with MCL by FISH. Secondary cytogenetic aberrations were detected in 14 patients by FISH. The most common abnormality was del(11q22.3) (57.1%), the rate of aberrations for del(17p13), + 12 and del(13q14) were 42.9%, 35.7% and 21.4%, respectively. Two (14.3%) and 4 (28.6%) patients were detected to have combinations of 2 and 3 aberrations., Conclusion: In addition to t(11; 14), most MCL patients have other chromosome aberrations, especially complex aberrant karyotype.

In this paper, Lujing water supply plant in Jiangsu was selected to carry out the investigation in order to understand the constitutes of the membrane fouling, comment on the membrane cleaning methods and obtain the proper cleaning sequences. In the experiments, water quality of the raw water was measured; membrane characteristics of the plant and membrane cleaning methods were thoroughly analyzed. The results indicated that the hydrophobic acids (HOA) and hydrophilic matters (HIM) are the major components in the raw water, 40.34% and 28.48% respectively in mass fraction. EEM's results also demonstrated that aromatic protein II are the main constitutes in the DOMs. In addition, the turbidity can reach around 0.1 NTU and the DOM can be removed partially by the PVC-UF membrane process during the water production. The constitutes of those emulations demonstrated that inorganic ions and NOM were both contributed to the membrane fouling. Ca and Si were the major inorganic contributors; aromatic protein II, SMP and fulvic acid were the major organic ones. According to SEM observation the sequence of the membrane cleaning should be HCl first, then NaOH.

Objective: To evaluate the efficacy of combination chemoimmunotherapy of fludarabine, cyclophosphamide and rituximab (FCR) in chronic lymphocytic leukemia (CLL)., Methods: Twenty-one patients with CLL were treated with FCR regimen which consisted of fludarabine (25 mg/m(2), days 2 to 4), cyclophosphamide (250 mg/m(2), days 2 to 4) and rituximab (375 mg/m(2), day 1) in a course of 28 days. The minimal residual disease (MRD) was determined by multiparameter flow cytometry. The correlation between the pretreatment characteristics and complete remission (CR) rate was analyzed., Results: Eleven patients (52.4%) achieved CR, 7 (33.3%) achieved partial remission (PR) with a overall response (OR) rate of 85.7%. With a median follow-up time of 19 (7 - 73) months, the overall survival (OS) was 86.0%, and the progression-free survival (PFS) was 72.0%. Pretreatment parameters independently associated with higher CR rates were Binet stage A + B, IgVH mutated and ZAP-70 less than 20%. MRD was less than 1% in 6 patients. The most common toxicities were myelosuppression and gastrointestinal reaction., Conclusion: FCR is an effective regimen for CLL patients.

This study was aimed to investigate laboratorial characteristics of immunophenotyping and concurrent karyotypic aberrations in acute myeloid leukemia with t(8;21)(q22;q22). A total number of 47 AML patients with t(8;21) were enrolled in this study and immunophenotypic antigens were detected by multiparameter flow cytometry. The results indicated that the additional karyotypic aberrations were found in 21 out of 47 AML patients with t(8;21) (q22;q22 (44.68%), single karyotypic aberration was observed in 26 out of 47 AML patients with t(8;21) (q22;q22) (55.32%). The positive rate of stem/progenitor cell markers of CD34, CD117 and HLA-DR were 87.2%, 97.9% and 95.7% respectively. Myeloid markers of CD13 and CD33 were 93.6% and 87.2%, and there were nearly no expression of T lineage antigens (CD2, CD3, CD5 and CD7) detected in t(8;21)-AML. CD19, one of a pan-B markers was found in 66.0% of all 47 t(8;21)-AML patients as well as CD56(66.7%), which was significant higher than other B lineage antigens (CD20 and CD22). It is concluded that AML with t(8;21) displays an exclusive immunophenotyping with significantly high expression of CD19 and CD56 as well as precursor cell markers (CD34, CD117 and HLA-DR) and combination detection of CD34/CD19/CD56 may become a predictive indicator of t(8;21) (q22;q22) cytogenetic abnormality.