The association between the serum concentration of CXC subfamily chemokine 13 and post-surgical clinical outcomes in cervical cancer patients.

OBJECTIVE: This study aimed to investigate the relationship between serum levels of CXC subfamily chemokine 13 (CXCL13) and clinical outcomes following radical surgery for cervical cancer. PATIENTS AND METHODS: A total of 70 cervical cancer patients admitted to our hospital between August 2021 and December 2022 were selected as the study group, while 30 healthy individuals who underwent regular physical examinations during the same period were selected as the control group. The levels of CXCL13 were measured in both groups, and a comparison was made between pre- and post-operative CXCL13 levels in the study group and the control group. Follow-up data on clinical outcomes were collected for the study group, and clinical data were compared between the recurrence/metastasis group and the non-recurrence/metastasis group. Logistic regression analysis was performed to identify factors influencing recurrence and metastasis by incorporating variables showing significant differences. Additionally, Pearson's correlation analysis was used to examine the relationship between CXCL13 and clinical data. RESULTS: Postoperative levels of CXCL13 in the study group showed a significant decrease compared to preoperative levels, and they were lower than those in the control group (p<0.05). Among the 70 patients in the study group, 23 experienced recurrence or metastasis, while 47 did not. Significant differences were observed between the recurrence/metastasis group and the non-recurrence/metastasis group in terms of histological grade, depth of cervical invasion, FIGO stage, parametrial infiltration, lymph node metastasis, and CXCL13 (p<0.05). Logistic regression analysis revealed that CXCL13, histological grade, depth of cervical invasion, FIGO stage, parametrial infiltration, and lymph node metastasis were all factors influencing recurrence and metastasis. There was a positive correlation between CXCL13 and histological grade, depth of cervical invasion, FIGO stage, parametrial infiltration, and lymph node metastasis (p<0.05). CONCLUSIONS: The level of CXCL13 is closely associated with the clinical outcome of cervical cancer after radical surgery and can serve as an important indicator for predicting clinical outcomes. Its application in clinical practice is highly recommended.

[Clinical analysis of long-term survival and influencing factors of chimeric antigen receptor T-cell therapy in relapsed/refractory acute B-cell lymphoblastic leukemia].

Objective: To analyze the survival and influencing factors of chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory acute B-cell lymphoblastic leukemia (R/R B-ALL) . Methods: Clinical information of patients who received CAR-T-cell therapy and achieved complete remission of R/R B-ALL between May 2015 and June 2018 at the Shaanxi Provincial People's Hospital was obtained. Kaplan-Meier analysis was used to evaluate the overall survival (OS) and leukemia-free survival (LFS) times of patients, and Cox regression analysis was performed to analyze the prognostic factors that affect patient survival after CAR-T therapy. Results: Among the 38 patients with R/R B-ALL, 21 were men, with a median age of 25 (6-59) years and a median OS time of 18 (95% CI 3-33) months. Multivariate Cox regression analysis showed that positive MLL-AF4 fusion gene expression was an independent risk factor for OS and LFS (OS: HR=4.888, 95% CI 1.375-17.374, P=0.014; LFS: HR=6.683, 95% CI 1.815-24.608, P=0.004). Maintenance therapy was a protective factor for OS and LFS (OS: HR=0.153, 95% CI 0.054-0.432, P<0.001; LFS: HR=0.138, 95% CI 0.050-0.382, P<0.001). In patients with MRD negative conversion, LFS benefit (HR=0.209, 95% CI 0.055-0.797, P=0.022) and OS difference was statistically insignificant (P=0.111). Moreover, patients with high tumor burden were risk factors for OS and LFS at the level of 0.1 (OS: HR=2.662, 95% CI 0.987-7.184, P=0.053; LFS: HR=2.452, 95% CI 0.949-6.339, P=0.064) . Conclusion: High tumor burden and high-risk genetics may affect the long-term survival rate of patients with R/R B-ALL receiving CAR-T, and lenalidomide-based maintenance therapy may improve their prognosis.

Postoperative pulmonary complications in older patients undergoing elective surgery with a supraglottic airway device or tracheal intubation.

The two most commonly used airway management techniques during general anaesthesia are supraglottic airway devices and tracheal tubes. In older patients undergoing elective non-cardiothoracic surgery under general anaesthesia with positive pressure ventilation, we hypothesised that a composite measure of in-hospital postoperative pulmonary complications would be less frequent when a supraglottic airway device was used compared with a tracheal tube. We studied patients aged ≥ 70 years in 17 clinical centres. Patients were allocated randomly to airway management with a supraglottic airway device or a tracheal tube. Between August 2016 and April 2020, 2900 patients were studied, of whom 2751 were included in the primary analysis (1387 with supraglottic airway device and 1364 with a tracheal tube). Pre-operatively, 2431 (88.4%) patients were estimated to have a postoperative pulmonary complication risk index of 1-2. Postoperative pulmonary complications, mostly coughing, occurred in 270 of 1387 patients (19.5%) allocated to a supraglottic airway device and 342 of 1364 patients (25.1%) assigned to a tracheal tube (absolute difference -5.6% (95%CI -8.7 to -2.5), risk ratio 0.78 (95%CI 0.67-0.89); p < 0.001). Among otherwise healthy older patients undergoing elective surgery under general anaesthesia with intra-operative positive pressure ventilation of their lungs, there were fewer postoperative pulmonary complications when the airway was managed with a supraglottic airway device compared with a tracheal tube.

[Preliminary analysis of seasonal pollen allergens of allergic rhinitis in a hospital of Nanchang City].

The study was aimed to analyze the seasonal pollen allergen spectrum of patients with allergic rhinitis (AR) in Nanchang city, and to provide evidence for improving the clinical diagnosis, treatment, prevention and epidemiology of seasonal AR. A retrospective analysis was conducted on the results of skin prick test (SPT) among 1 752 patients with AR in outpatient at Department of Otolaryngology, the First Affiliated Hospital of Nanchang University from September 2020 to August 2021 (a total of 1 069 males and 683 females, age ranged from 2 to 84 years old). SPSS 22.0 software was used to analyze the positive rates of main allergens and their differences in gender, age, and month of visit. Differences among groups were compared by student t test, Wilcox rank sum test, or χ2 test. The results showed that among 1 752 SPT-positive patients, the number of simple seasonal AR and the number of perennial combined seasonal AR were 102 (5.82%) and 281 (16.04%), respectively. There was no significant difference between male and female patients in positive seasonal pollen allergens (χ2=2.181, P>0.05), but the positive rate of indoor seasonal pollen allergens in males was higher than that in females (χ2=7.901, P<0.05). The seasonal pollen allergens ranking top 5 of the positive rates were willow (6.62%, 116/1 752), humulus scandens (5.71%, 100/1 752), rape (5.54%, 97/1 752), grey pigweed (4.62%, 81/1 752) and birch (3.60%, 63/1 752). The positive rates of indoor and seasonal pollen allergens increased first and then decreased in different age groups, and the highest positive rates of seasonal pollen allergens were in the age group of 31-40 years old, with statistical significance compared with other groups (χ2=61.269, P<0.05). The seasonal allergen positive rate showed two peaks in time: March to May and September to November. The positive rate of pollen in spring was 60.27% (132/219), which was significantly higher than that in autumn (39.73%,87/219) (χ2=9.247, P<0.05). The positive rate of pollen combination in spring and autumn was 68.29% (112/164), which was significantly higher than that in spring and autumn alone (18.9%,31/164) and (12.8%, 21/164) (χ2=14.731, P<0.05). In summary, pollen allergy in Nanchang City cannot be ignored, accounting for more than 20% of the total number of AR. The incidence of seasonal AR in Nanchang City showed two peaks (March to May and September to November). The common allergens for seasonal AR in Nanchang City were willow, humulus scandens, rape, grey chenopods and birch.

[The role of STAT-6/KLF-4/PPAR-γ activation in alveolar macrophage polarization changes in silica-induced pulmonary fibrosis].

Objective: To observe the effect of silicon dioxide (SiO(2)) on the polarization of alveolar macrophages (AMs) , and to explore the expressions and the significance of signal transducer and activator of transcription-6 (STAT-6) /Krüppel-like factor-4 (KLF-4) /peroxisome proliferators-activated receptors-γ (PPAR-γ) signaling molecules in AMs. Methods: In November 2020, C57BL/6 mice were randomly divided into crystalline SiO(2) group and normal saline (NS) group, and 12 mice in each group. Mice were intratracheally instillated with 100 µl crystalline SiO(2) suspension (20 mg/ml) or 100 µl NS, and were sacrificed after 28 days. Masson staining was used to observe the degree of pulmonary fibrosis of mice and hydroxyproline (HYP) level were assessed. The proportions of M1-typed and M2-typed AMs in bronchoalveolar lavage fluid (BLAF) were analyzed by flow cytometry. The mRNA relative expression levels of inducible nitric oxide synthase (iNOS) , arginidase-1 (Arg-1) , interleukin (IL) -1ß, tumor necrosis factor-α (TNF-α) , IL-6, IL-10, transforming growth factor-ß (TGF-ß) , STAT-6, KLF-4 and PPAR-γ were detected by real-time fluorescence quantitative PCR. Activities of iNOS and Arg-1, as well as contents of IL-1ß, TNF-α, IL-6, IL-10 and TGF-ß were assessed by the enzyme-linked immunosorbent. The protein relative expression levels of phosphorylation-signal transducer and activator of transcription-6 (p-STAT-6) , KLF-4 and PPAR-γ were evaluated by immunofluorescence. Results: After 28 days of treatment, the structure of the lung tissue of the mice was destroyed, and the deposition of collagen was significantly increased in the crystalline SiO(2) group. Compared with NS group, HYP level of lung tissue in crystalline SiO(2) group were increased, the proportion of M2-typed AMs in crystalline SiO(2) group was increased, the proportion of M1-typed AMs in crystalline SiO(2) group was decreased, the mRNA relative expressions and contents of Arg-1, IL-10, TGF-ß in crystalline SiO(2) group were significantly increased, the mRNA relative expressions and contents of iNOS, IL-1ß, TNF-α, IL-6 in crystalline SiO(2) group were significantly decreased, the mRNA of STAT-6, KLF-4, PPAR-γ and the protein relative expression levels of p-STAT-6, KLF-4, PPAR-γ were significantly increased in crystalline SiO(2) group, and the the differences were statistically significant (P<0.05) . Conclusion: Crystalline SiO(2) may mediate the process of pulmonary fibrosis through promote AMs polarization toward M2-typed by activating the STAT-6/KLF-4/PPAR-γ signaling pathway.

[Correlation analysis between blood routine-derived inflammatory markers and respiratory function in pneumoconiosis patients].

Objective: To analyze the correlation between blood routine-derived inflammation indicators and respiratory function in patients with pneumoconiosis. Methods: In January 2021, 492 male pneumoconiosis patients hospitalized in Hefei Institute of Occupational Disease Control and Prevention from 2012 to 2020 were randomly selected as the case group, 492 dust exposed non pneumoconiosis workers who underwent occupational health examination at the same time were taken as the control group. The occupational history and clinical examination data of the two groups of subjects were collected, the correlation between blood routine-derived inflammatory indexes and pulmonary function and blood gas analysis was analyzed retrospectively. Results: Compared with the control group, the lymphocyte monocyte ratio (LMR) in the case group was decreased, and the neutrophil lymphocyte ratio (NLR) was increased, and the difference was statistically significant (P<0.05) . There were significant differences in forced vital capacity as a percentage of the predicted value (FVC) , forced expiratory volume in the first second as a percentage of the predicted value (FEV(1)%) , one second rate (FEV(1)/FVC) , partial pressure of oxygen (PaO(2)) , partial pressure of carbon dioxide (PaCO(2)) , and pH among pneumoconiosis patients at different stages (P<0.05) . FVC%, FEV(1)%, FEV(1)/FVC, and PaO(2) decreased with the increase of the stage, the trend test was statistically significant (tau-b=-0.24, -0.34, -0.37, -0.17, P<0.05) , PaCO(2) and pH increased with the increase of the stage, and the trend test was statistically significant (tau-b=0.10, 0.08, P<0.05) . There were statistically significant differences in LYM, LMR, NLR, platelet lymphocyte ratio (PLR) in patients with pneumoconiosis at different stages (P<0.05) , and LYM and LMR decreased with the increase of stage, trend test showed that there was statistically significant (tau-b=-0.11, -0.13, P<0.05) . There were significant differences in FVC%, FEV(1)%, FEV(1)/FVC, PaO(2), pH, LMR, NLR, PLR among patients with different types of pneumoconiosis (P<0.05) . LMR in pneumoconiosis patients was significantly positively correlated with FVC%, FEV(1)%, FEV(1)/FVC and PaO(2) (r(s)=0.342, 0.324, 0.203, 0.207, P<0.05) , NLR was significantly negatively correlated with FVC%, FEV(1)%, FEV(1)/FVC and PaO(2) (r(s)=-0.193, -0.202, -0.164, -0.177, P<0.05) , PLR was significantly negatively correlated with FVC%, FEV(1)%, FEV(1)/FVC and PaO(2) (r(s)=-0.194, -0.193, -0.106, -0.113, P<0.05) . Multiple linear regression analysis showed that LMR in pneumoconiosis patients was positively related with FVC%, FEV(1)% and PaO(2) (P<0.05) . Conclusion: LMR in patients with pneumoconiosis has a certain correlation with lung function and blood gas analysis, LMR is expected to become a sensitive indicator for evaluating pneumoconiosis.

[Comparison of tolerance to decentration and tilt in the early postoperative period between the continuous range and bifocal intraocular lens implantation in myopic eyes].

Objective: To compare decentration and tilt tolerances between continuous range intraocular lens (IOL) and bifocal IOL in myopia during the early stages post intraocular implantation. Method: A retrospective cohort study was conducted using follow-up data of 145 patients (145 eyes) who underwent phacoemulsification combined with IOL implantation in the Eye & ENT Hospital of Fudan University from January 2018 to December 2020. According to whether the axial length was less than 24.5 mm, patients were divided into non-myopic and myopic groups. According to IOL type, patients were divided into extend depth of focus (EDOF) ZXR00 IOL group (myopic 38 eyes, non-myopic 41 eyes) and bifocal ZMB00 IOL group (myopic 23 eyes, non-myopic 43 eyes). The distance and near visual acuity (log of the minimum angle of resolution visual acuity), IOL tilt and decentration, intraocular high-order aberration (HOA), coma, trefoil, spherical aberrations, modulation transfer function (MTF), as well as VF-14 index and the incidence of dysphotopsia were compared between the 2 groups at 3 months after surgery. Statistics were performed using Student's t-test, χ2 test, Pearson correlation analysis and multiple linear regression analysis. Results: In either the myopic or non-myopic group, no significant differences were found in age, gender, eye laterality, axial length and IOL degree between eyes with the two different types of IOLs (all P>0.05). At 3 months after surgery, there was no significant difference in uncorrected and best-corrected distance visual acuity between the ZXR00 IOL group and the ZXR00 IOL group, while uncorrected near visual acuity was better in the ZMB00 IOL group than the ZXR00 IOL group (t=10.41, P<0.01). The total postoperative IOL decentration in the ZXR00 IOL group and ZMB00 IOL group in myopic eyes were (0.32±0.17) and (0.38±0.16) mm, respectively, which were greater than those in non-myopic eyes [(0.22±0.12), (0.28±0.12) mm; t=3.16, 2.57; both P<0.05]. However, there were no significant differences in IOL tilt between myopic and non-myopic eyes in the 2 groups (both P>0.05). There were no significant differences in postoperative IOL tilt and decentration between the 2 groups regardless of myopia or non-myopia (all P>0.05). In myopic eyes, HOA, coma aberration and spherical aberration in the ZXR00 IOL group were significantly lower than those in the ZMB00 IOL group, while the total ocular MTF (38.15±10.12) was significantly higher than that in the ZMB00 IOL group (30.46±10.53) (all P<0.05). Pearson correlation analysis and multiple linear regression analysis showed a positive correlation between postoperative HOA and both IOL tilt and decentration in the ZMB00 IOL group (r=0.627, 0.726; ß=0.446, 0.587; all P<0.01). However, no such relationship was found in the ZXR00 IOL group (all P>0.05). In myopic eyes, when the IOL tilt aberration and decentration were greater than the median, the HOAs in the ZXR00 IOL group [(0.33±0.14), (0.27±0.11) µm] were lower than those in the ZMB00 IOL group [(0.88±0.56), (0.96±0.45) µm], while the total ocular MTF (42.87±10.97, 40.22±9.30) were higher than those in the ZMB00 IOL group (25.02±8.99, 29.87±10.19) (all P<0.05). In myopic eyes, the proportion of patients with visual interference symptoms in the ZXR00 IOL group [42.11% (16/38)] was significantly lower than that in the ZMB00 IOL group [78.26%(18/23), χ²=7.59, P<0.05]. Conclusion: During the early stages after IOL implantation in myopic eyes, EDOF IOL is more tolerant to decentration and tilt than bifocal IOL.

[The influence of residual astigmatism on the postoperative visual quality in patients with implantation of an extended depth of focus intraocular lens].

Objective: To investigate the influence of residual astigmatism on the postoperative visual acuity in cataract patients with implantation of an extended depth of focus intraocular lens (IOL). Methods: Retrospective cohort study. A total of 56 eyes of 56 cataract patients who underwent phacoemulsification combined with extended depth of focus IOL implantation from January 2019 to December 2020 at Eye & ENT Hospital of Fudan University were included. There were 29 males and 27 females in all patients, and the age was (65±9) years. Patients were divided into two groups according to their postoperative residual astigmatism: low astigmatism group (<0.75 D, 28 eyes) and high astigmatism group (0.75 to 1.50 D, 28 eyes). At 3 months after surgery, measurements were completed, including postoperative uncorrected distance (5 m) visual acuity, uncorrected intermediate (80 cm) visual acuity, uncorrected near (40 cm) visual acuity, best corrected visual acuity (all the visual acuity was converted to the logarithm of the minimum angle of resolution visual acuity), defocus curves, quick contrast sensitivity function, wavefront aberration, and VF-14 questionnaire scores. The independent samples t-test and Mann-Whitney U test were used for data analysis. Results: The low astigmatism group and high astigmatism group's uncorrected distance visual acuity [M (Q1, Q3)] were 0.05 (-0.06, 0.10), 0.08 (0.00, 0.22), their uncorrected intermediate visual acuity were 0.11 (0.00, 0.20), 0.14 (0.10, 0.21), their uncorrected near visual acuity were 0.28 (0.20, 0.32), 0.26 (0.20, 0.30), and their best corrected visual acuity were 0.17 (0.05, 0.30), 0.14 (0.04, 0.22), respectively. The differences were not statistically significant (all P>0.05). No significant difference was found in the defocus curves from +1.00 to -4.00 D, at intervals of +0.50 D, between the two groups (all P>0.05). No significant difference was found in the quick contrast sensitivity of low, middle and high frequency of dark vision between the low astigmatism group and high astigmatism group (all P>0.05), and the area under Log contrast sensitivity function of the two groups were 0.87±0.28 and 0.77±0.30 (P>0.05). The total whole-eye aberrations were 0.59±0.18 and 0.74±0.51, and the total higher-order aberrations were 0.30±0.13 and 0.37±0.25 in the two groups at 4.0-mm pupil diameter. The differences were not statistically significant when the total whole-eye aberration, total higher-order aberration, coma, cloverleaf aberration, and spherical aberration were compared (all P>0.05). The differences of the total VF-14 visual scores, near visual acuity scores and the distance visual acuity scores of the two groups were not statistically significant (all P>0.05). Conclusion: Cataract patients with residual postoperative astigmatism 0.75 to 1.50 D can obtain as good visual quality as those with postoperative residual astigmatism<0.75 D after implantation of an extended depth of focus IOL.

Fluoride induced down-regulation of IKBKG Gene expression inhibits hepatocytes senescence.

BACKGROUND: Accumulating evidences have confirmed that liver is one of the more severely damaged organs during chronic fluorosis. However, the detail mechanism is unclear to data. At present, the objective of this study was to investigate the relationship between down-regulation of IKBKG gene expression and hepatocyte senescence induced by sodium fluoride (NaF). METHODS: Chronic fluorosis rats and NaF-exposure human liver L02 cells were reproduced the model of hepatocyte senescence in vivo and in vitro. The mRNA and protein levels of p16, p21 and IKBKG, the IL-8 level were determined. The role of IKBKG in fluoride-induced senescence of hepatocytes was explored by knock down in hepatocytes in vivo and in vitro. RESULTS: The number of senescence-positive cells in rat liver tissues was increased as well as the level of IL-8 and the expression levels of p16, p21 and IKBKG in fluoride exposure to rat depending on the fluoride concentration. The similar results were obtained in NaF treated liver L02 cells, and the number of cells that stagnated in the G2 phase increased significantly. Further, our results confirmed that decreasing the expression of IKBKG in hepatocytes could reduce fluoride-induced hepatocyte senescence and the changes of senescence-related indicators both in vivo and in vitro. CONCLUSION: These results indicated that the elevated expression of IKBKG was positive relation with the fluoride-induced senescence in hepatocytes, suggesting the hepatocyte senescence might have a special relationship with fluoride-caused liver damage. Because of the present results limitation, the mechanism of fluoride induced senescence in hepatocytes should be concentrated in the future in detail, especially the novel targets for fluoride induced liver injury.

Experimental observations and density functional simulations on the structural transition behavior of a two-dimensional transition-metal dichalcogenide.

In this work, we show an obvious evidence of nondestructive Raman spectra for the structural transition, i.e., the existence of a charge density wave (CDW) in monolayer 2H-TaS2, which can exhibit a much higher transition temperature than bulk and results in additional vibrational modes, indicating strong interactions with light. Furthermore, we reveal that the degenerate breath and wiggle modes of 2H-TaS2 originated from the periodic lattice distortion can be probed using the optical methods. Since recently several light-tunable devices have been proposed based on the CDW phase transition of 1 T-TaS2, our study and in particular, the theoretical results will be very helpful for understanding and designing electronic devices based on the CDW of 2H-TaS2.

[Study on syndromic deafness caused by novel pattern of compound heterozygous variants in the CDH23 gene].

Objective: To explore the pathogenic variants of a family with syndromic deafness by high-throughput sequencing. Methods: The family was from Puyang City, Henan Province, and had four members, including two with syndromic deafness. The proband and his sister had congenital deafness, and their parents had normal phenotypes. The clinical phenotype of the family was characterized using clinical examinations and pedigree analysis. The clinical examinations included imaging examination, audiometry (pure tone audiometry, acoustic immittance, brainstem auditory evoked potential, and otoacoustic emission), vestibular function test, and ophthalmic examination (visual acuity test, visual field test, fundus examination, visual evoked potential, and electroretinogram). Target exome sequencing of 129 known deafness genes and bioinformatics analysis were used to screen suspected pathogenic variants. Sanger sequencing and minigene assay were used to verify and functionally investigate the mutation detected, respectively. According to the standards and guidelines for interpreting genetic variants proposed by the American College of Medical Genetics and Genomics, the variants c.6049G>A and c.8699A>G were classified as pathogenic/likely pathogenic, and the variant c.9856C>G was classified as variants of uncertain significance. Results: The probands and his sister had severe sensorineural hearing loss with decreased binocular vision, night blindness, decreased peripheral visual field sensitivity and partial visual field defect, and normal vestibular function. Both of them had three CDH23 mutations, including CDH23 (NM_022124.5) c.6049G>A (p.Gly2017Ser),c.9856C>G (p.His3286Asp), and c.8699A>G (p. Asp2900Gly), The first two were inherited from the father, and the last one was from the mother. The missense variants c.9856C>G and c.8699A>G were not included in the gnomad database. The missense mutation c.6049G>A was located in the last position of exon 46 and was predicted to affect splicing by bioinformatics software. The minigene experiment showed that the mutation cause exon skipping of exon 46, resulting in an abnormal protein. Conclusions: Compound heterozygous variations of the CDH23 are the leading cause of USH1D in the family. This study confirms that the compound heterozygosity of splicing and missense variants of the CDH23 gene could lead to USH1D.

Knockdown of HMGB2 inhibits proliferation and invasion of renal tumor cells via the p-38MAPK pathway.

OBJECTIVE: To investigate the function of HMGB2 in renal tumor ACHN cells in vitro and in vivo and to study the underlying molecular mechanisms. PATIENTS AND METHODS: Kaplan-Meier analysis was used to study the relationship between expression of HMGB2 and prognosis of renal tumor. MTT assay was employed to examine cell proliferation and flow cytometry analysis was used to study the role of HMGB2 in cell apoptosis in ACHN cells. Transwell assays were used to explore the migration and invasion of ACHN cells. The effect of HMGB2 on tumor growth was investigated in vivo. Western blot was performed to evaluate the expression levels of p-JNK, p-ERK and p-p38MAPK. RESULTS: HMGB2 was upregulated in renal tumor and correlated with worse overall survival in renal tumor patients. Down-regulation of HMGB2 suppressed ACHN cells proliferation, invasion and migration in vitro. Moreover, down-regulation of HMGB2 inhibited tumor growth in vivo and HMGB2 exerts the oncogene function partly via the inhibition of p-p38MAPK activation. CONCLUSIONS: Our results provide novel insights into neuropathic pain and help to explore therapeutic targets in the treatment.

[Effect of consolidation before allogeneic hematopoietic stem cell transplantation for non-favorable acute myeloid leukemia patients with first complete remisson and negative minimal residual disease].

Objective: To probe the prognostic value of consolidation chemotherapy in non-favorable acute myeloid leukemia (AML) patients who were candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT) with first complete remission (CR(1)) and negative minimal residual disease (MRD(-)) . Methods: A retrospective analysis was conducted on 155 patients with non-favorable AML who received allo-HSCT in CR(1)/MRD(-) from January 2010 to March 2019. The survival data were compared between patients who received and those not received pre-transplant consolidation chemotherapy. Results: A total of 102 patients received pre-transplant consolidation chemotherapy (consolidation group) , and 53 cases directly proceeded to allo-HSCT when CR(1)/MRD(-) was achieved (nonconsolidation group) . The median ages were 39 (18-56) years old and 38 (19-67) years old, respectively. Five-year post-transplant overall survival [ (59.3±7.5) % vs (62.2±6.9) %, P=0.919] and relapse-free survival [ (53.0±8.9) % vs (61.6±7.0) %, P=0.936] were not significantly different between the two groups (consolidation vs nonconsolidation) . There was a weak relationship between consolidation therapy and cumulative incidence of relapse [consolidation: (21.9±5.4) % vs nonconsolidation: (18.3±6.0) %, P=0.942], as well as non-relapse mortality [consolidation: (22.4±4.3) % vs nonconsolidation: (28.4±6.5) %,P=0.464]. Multivariate analysis indicated that pre-transplant consolidation and the consolidation courses (< 2 vs ≥2 courses) did not have an impact on allo-HSCT outcomes. Conclusion: Allo-HSCT for candidate patients without further consolidation when CR(1)/MRD(-) was attained was feasible.

[Clinical and prognostic values of TP53 mutation in patients with acute myeloid leukemia].

Objective: To explore the clinical and prognostic values of TP53 gene mutation in patients with acute myeloid leukemia (AML) . Methods: A retrospective analysis of 265 newly diagnosed AML patients with next-generation sequencing (NGS) data in the Hematology Department of Changhai Hospital from January 2010 to January 2019 was performed. Mutation analysis was carried out by targeted sequencing technology including 200 hematological malignancy related genes. The association of TP53 mutation with clinical features was analyzed. Results: Alterations in TP53 were found in 20 (7.5%) patients, including 17 case (6.4%) of missense mutations, 2 cases (0.7%) of frame-shift deletion mutations and 1 case (0.4%) of splicing sites mutation. A total of 23 kinds of TP53 mutations were detected, most of them (16, 69.6%) were located in the DNA binding domain of exon 5-8, 4 in the DNA binding domain of exon 3-4, 2 in exon 10 and 1 in splice site, respectively. The median age of patients with TP53 alterations was higher than those without [52 (26-72) years old vs 45 (14-75) years old, P= 0.008]. The frequency of complex karyotypes was higher in patients with TP53 alterations than those without [45.0% (9/20) vs 6.1% (15/245) , P<0.001]. Median overall survival (OS) of patients with TP53 alterations was shorter than those without[14.1 (95%CI 6.78-21.42) months vs 31.4 (95%CI 13.20-49.59) months, P=0.029]. The OS of patients treated with "Decitabine + CAG" was superior than that of patients treated with "3 + 7" regimen [30.0 (95%CI 27.35-38.84) months vs 12.5 (95%CI 5.80-19.19) months, P=0.018]. Multivariate analysis indicated that TP53, DNMT3A and USH2A alterations, WBC ≥ 12.45×10(9)/L had negative impacts on OS. Conclusion: The frequency of TP53 mutation was 7.5% in our cohort. Most mutations were located in the DNA binding domain. TP53 alterations were strongly associated with older age, complex karyotype and shorter OS. Decitabine-based induction chemotherapy and hematopoietic stem cell transplantation may improve OS, more cases and/or multicenter randomized studies are needed for further confirmation.

[Using next generation sequencing technology to analyze gene mutations in patients with acute myeloid leukemia and the impact on prognosis].

Objective: To analyze the distribution of gene mutations in newly diagnosed acute myeloid leukemia (AML) patients, based on next generation sequencing technology (NGS) and to evaluate their value in AML risk stratification. Methods: The study analyzed 453 newly diagnosed AML(excluded acute promyelocytic leukemia, APL) patients from seven hospitals in Shanghai, from January 1st 2014 to December 31th 2017. RNA and DNA were extracted from pretreatment bone marrow mononuclear cells and targeted sequencing of AML genes were performed. The data of different groups was compared. Results: A total of 453 newly diagnosed AML patients were enrolled in the study, including 247 males and 206 females with a median age of 49.5 (range,11-85) years. A total of 540 mutations/fusion genes were detected in 289 patients, 29.1% (132/259) of whom with two or more mutations/fusion genes. In all patients, NPM1 was the most common mutation(12.8%), followed by ETO and TET2 mutation (11.92% and 11.04%, respectively) . And WT1 over-expression accounted for 10.6%. Patients over the age of 50 were with a higher frequency of mutations associated with epigenetic modification, 11.93% for ASXL1, 13.99% for DMNT3A, 6.58% for IDH1/IDH2, and 13.17% for TET2. The frequency of DMNT3A mutations was three times higher than that of patients under 50 years of age (P=0.017). In this study, a relatively low proportion of genetic mutations was observed in low-risk karyotype group. In the medium-risk karyotype group, the relatively high mutation frequencies were observed in NPM1, TET2, FLT3-ITD, DNMT3A, ASXL1, and CEBPA genes. In the poor-risk karyotype group, the mutation frequencies of ASXL1, TET2, DNMT3A and PHF6 genes were more than 10%, especially ASXL1 and PHF6 mutation frequencies were significantly higher than other molecular risk stratification groups (P<0.05). Of the 254 patients (56%) with normal karyotype AML (NK-AML), 56 patients were detected to have gene mutations about epigenetic modification. The median OS of this group was worse than that of patients without related mutations, while the median LFS had no significant difference. In patients with NK-AML older than 50 years, the OS and LFS of patients with epigenetic modification related gene mutations was 12 months and 10 months, versus 18 months and 12 months of patients without mutations. Conclusions: The gene mutations frequencies in AML patients with different age and molecular risk stratification groups are different. Epigenetics gene mutation frequencies, such as DNMT3A, ASXL1, IDH1/IDH2 and TET2,are higher in patients older than 50 years. A shorter OS can be observed in older patients(>50 years) with epigenetics gene mutation.

[Efficacy of Hyper-CVAD/MA and CHALL-01 regimens in the treatment of Philadelphia chromosome-positive adult acute lymphoblastic leukemia patients under 60 years old].

Objective: To compare the difference of efficacy between traditional Hyper-CVAD/MA regimen and the adolescents inspired chemotherapy regimen, CH ALL-01, in treatment of adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) . Methods: In this study we retrospectively analyzed 158 Ph(+) ALL patients receiving Hyper-CVAD/MA regimen (n=63) or CHALL-01 regimen (n=95) in our center and Changzheng hospital from January 2007 to December 2017, excluding patients with chronic myeloid leukemia in blast crisis. Tyrosine kinase inhibitor (TKI) was administered during induction and consolidation chemotherapy. Patients who underwent hematopoietic stem cell transplantation received TKI as maintenance therapy. Results: Of them, 91.1% (144/158) patients achieved complete remission (CR) after 1-2 courses of induction. CR rate was 90.5% (57/63) for patients in Hyper-CVAD/MA group and 91.6% (87/95) for patients in CHALL-01 group. There was no difference in CR rates between the two groups (χ(2)=0.057, P=0.811) . The last follow-up was June 2018. A cohort of 134 CR patients could be used for further analysis, among them, 53 patients received Hyper-CVAD/MA regimen and other 81 patients received CHALL-01 regimen. The molecular remission rates were significantly higher in CHALL-01 group (complete molecular response: 44.4%vs 22.6%; major molecular response: 9.9% vs 18.9%) (χ(2)=7.216, P=0.027) . For the patients in Hyper-CVAD/MA group, the 4-year overall survival (OS) was 44.81% (95%CI: 30.80%-57.86%) and the 4-year disease free survival (DFS) was 37.95% (95%CI: 24.87%-50.93%) . For patients received CHALL-01 regimen, the 4-year OS was 55.63% (95%CI: 39.07%-69.36%) (P=0.037) and 4 year DFS was 49.06% (95%CI: 34.24%-62.29%) (P=0.015) , while there was no significant difference in 4 year cumulative incidence of relapse (CIR) (P=0.328) or cumulative incidence of nonrelapse mortality (CI-NRM) (P=0.138) . The rate of pulmonary infection was lower in patients received CHALL-01 regimen compared with patients received Hyper-CVAD regimen (43.4% vs 67.9%, χ(2)=7.908, P=0.005) . Conclusions: Outcome with CHALL-01 regimen appeared better than that with the Hyper-CVAD/MA regimen in Ph(+) ALL, which has lower incidence of pulmonary infection, higher molecular remission rate and better OS and DFS.