[Clinicopathologic characteristics and survival analysis of primary large B-cell lymphoma of the central nervous system].

Objective: To retrospectively analyze the clinical and pathologic characteristics, response to treatment, survival, and prognosis of patients with primary large B-cell lymphoma of the central nervous system (PCNSLBCL) . Methods: Clinical and pathologic data of 70 patients with PCNSLBCL admitted to Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2010 to November 2022 were collected for retrospective analysis. Survival analysis was performed using the Kaplan-Meier method and log-rank test, and prognosis analysis was conducted using the Cox proportional hazards model. Results: Among 70 patients with PCNSLBCL, complete remission (CRs) were achieved in 49 (70.0% ) and partial remission in 4 (5.7% ) after the first-line induction therapy; the overall remission rate was 75.7%. The 2-year progression-free survival (PFS) rate was 55.8% and the median progression-free survival (mPFS) time was 35.9 months, whereas the 2-year overall survival (OS) rate was 79.1% with a median OS time not reached. After CR induced by first-line therapy, cumulative incidence of relapse (CIR) was lower in patients who had received auto-HSCT than in those who had not received consolidation therapy (P=0.032), whose 2-year PFS rate was 54.4% and mPFS time was 35.9 months; comparatively, the 2-year PFS rate in patients having received oral maintenance of small molecule drugs reached 84.4% with a mPFS time of 79.5 months (P=0.038). Multivariant analysis demonstrated that Class 3 in the Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic model is an independent adverse prognostic factor of OS in patients with PCNSLBCL (HR=3.127, 95% CI 1.057-9.253, P=0.039) . Conclusions: In patients with PCNSLBCL achieving CR after the first-line induction therapy, auto-HSCT as consolidation therapy would lead to a decreased CIR, and PFS time could be prolonged by oral maintenance of small molecule drugs. Class 3 MSKCC prognostic model is independently associated with poorer OS.

[A prospective cohort study on visual development in infants and young children].

Objective: This study aimed to analyze the trends and characteristics of early visual development in infants and young children. Methods: A prospective cohort study was conducted, including full-term infants born between 2008 and 2013 at the Maternal and Child Health Hospital in Sanhe City, Hebei Province, China. Visual acuity was assessed at three time points 42 days after birth, 9 months of age, and 18 months of age, using the Teller Acuity Card Ⅱ (TAC Ⅱ) grating visual acuity test. At 3 years of age, visual acuity was assessed using the Lea Symbols chart and converted to grating visual acuity. Visual acuity of both eyes was measured at 42 days, 9 months, and 18 months. For children at 9 and 18 months, monocular visual acuity was also assessed, while at 3 years of age, monocular visual acuity was measured. Visual acuity measurements at different time points and changes in visual acuity within each period were recorded. The visual development of the participants was analyzed and compared with previous literature results. Results: A total of 1 496 children were included in the study, including 773 males (51.67%) and 723 females (48.33%). The binocular visual acuity at 42 days, 9 months, and 18 months was 0.9 (0.6, 1.1), 6.4 (6.4, 9.6), and 9.6 (9.6, 9.6) cycles per degree (cpd), respectively, with statistically significant differences (P<0.001). Visual acuity increased by a factor of 3.21±0.70 between 42 days and 9 months, and by a factor of 0.23±0.48 between 9 and 18 months. At 9 months of age, the monocular visual acuity in the right and left eyes was 6.4 (4.8, 6.4) cpd, which remained the same at 18 months, and the median visual acuity at 3 years of age for both eyes was 18.75 cpd, with a Snellen visual acuity of 20/32 (20/40, 20/32). The differences in binocular visual acuity at each time point were not statistically significant (all P>0.05). At 9 months of age, 68.7%(633/921) of children had visual acuity of ≥6.5 cpd, which increased to 92.7%(342/369) at 18 months. Monocular visual acuity increased by a factor of 0.26±0.46 between 9 and 18 months, and by a factor of 1.36±0.52 between 18 months and 3 years. At 9 months of age, 72.01% (921 out of 1 279) of children who completed binocular visual acuity testing also underwent monocular visual acuity testing, while this proportion decreased to 35.83% (369 out of 1 030) at 18 months. Visual acuity improved with increasing age (P<0.001). The visual acuity of children at each age group in this study was higher than that reported in the literature for children in Guangzhou (P<0.001). Conclusions: The visual acuity of healthy infants and young children below 3 years of age improves with age. Visual development progresses rapidly before 9 months of age, slows down afterward, and then resumes rapid growth at 18 months of age.

[Intraseasonal variation of the association between cold temperature and mortality risk in Shandong Province].

Objective: To explore the intraseasonal variation in mortality risk from cold temperature exposure in Shandong Province. Methods: Mortality data in Shandong province from 2013 to 2018 were collected from the cause of death surveillance system of Shandong Center for Disease Control and Prevention. The basic information mainly included the date of death, age, gender, education level, cause of death, home address, etc. The daily meteorological data from China Meteorological Data Network mainly included the grid coordinate data of 0.01°×0.01° latitude and longitude, such as daily average temperature (℃) and daily average relative humidity (%). The cold season was from November to February. The first two months were the early cold season and the last two months were the late cold season. The extreme cold temperature was defined as the 10th percentile of the temperature range of cold season. Time-stratified case crossover design with distributed lag non-linear model analyzed the association between temperature and mortality and the association between extreme low temperature and mortality in different lag days in the cold season, and compared the intraseasonal differences between early (November-December) and late (January-February) cold season. Results: The temperature ranged from -17.3 ℃ to 18.6 ℃ in Shandong Province during the cold season from 2013 to 2018, and the P10 (extreme low temperature) was -13.7 ℃. The average daily temperature in the early cold season was (3.63±4.66) ℃. The temperature in the late cold season was (-0.09±3.70) ℃. The average daily relative humidity was (63.89±14.75) % in the early cold season and (62.27±14.19) % in the late cold season. This study included 1 473 300 deaths in the cold season in Shandong Province between 2013 and 2018. There were 824 601 (55.97%) males and 349 824 (23.75%) cases aged<65 years. There were 803 691 (54.55%) deaths due to circulatory diseases and 140 415 (9.53%) deaths due to respiratory diseases. The results of DLNM showed that the cumulative OR of extreme low temperature in the four months of cold season was 1.74 (95%CI: 1.63, 1.86) with the optimal temperature of 18.6 ℃ as the reference. The cumulative OR values of early and late cold season were 1.50 (95%CI: 1.32, 1.71) and 2.56 (95%CI: 2.12, 3.09), respectively (P<0.001). The lag effect lasted for 12 d. Conclusion: There is an intraseasonal variation of the association between cold temperature and mortality risk in Shandong Province. The mortality risk related to cold temperature in the late cold season is higher than that in the early cold season.

[Efficacy of RCDOP regimen in the treatment of patients with diffuse large B-cell lymphoma].

Objective: To investigate the efficacy of RCDOP (Rituximab, cyclophosphamide, liposome doxorubicin, vincristine and prednisone) regimen in patients with de novo diffuse large B-cell lymphoma (DLBCL), especially in those patients with multiple extra-nodal involvement or Bulky diseases. Methods: A total of 87 newly diagnosed DLBCL patients who received RCDOP regimen from October 2012 to October 2017 were enrolled into this study. Survival functions were estimated using the Kaplan-Meier method and compared by the log-rank test, and χ(2) tests were used for categorical data. Results: Among the 87 DLBCL patients treated with RCDOP regimen, 81 patients achieved complete remission (CR) or partial remission (PR), with ORR as 93.1%. Patients were further classified into groups, according to the risk factors, such as IPI scores, multiple extra-nodal involvement, bulky disease, age>60, tumor Ki-67>80%, elevated serum LDH level and advanced Ann Arbor stage. The progression-free survival (PFS, P=0.084) and overall survival (OS, P=0.515) had no statistical difference among the IPI low risk (0-1 score) group, intermediate risk (2-3 scores) group and high risk (4-5 scores) group. Similarly, no statistical difference were fou nd in PFS and OS of patients with extra-nodal involvements ≥2 (P=0.303 and P=0.624), with bulky disease (P=0.518 and P=0.466), with age>60 (P=0.600 and P=0.183), with elevated serum LDH level (P=0.054 and P=0.880), with advanced Ann Arbor stage (P=0.075 and P=0.286), and with tumor Ki-67 over 80% (P=0.190 and P=0.109), when compared with those of patients without these risk factors. Conclusion: RCDOP can improve the therapeutic effect and prognosis of DLBCL patients with certain high risk factors, such as intermediate and high IPI risks, multiple extra-nodal involvements, bulky disease, age over 60, elevated LDH level, advanced Ann Arbor stage and tumor Ki-67 over 80%.

[The roles of holothurian glycosaminoglycan combined with cisplatin on proliferation and chemotherapeutic response in A549 human lung adenocarcinoma cell].

Objective: To investigate the effects and mechanism of Holothurian Glycosaminoglycan (hGAG) alone in combination with cisplatin (DDP) on apoptosis of pulmonary adenocarcinoma cell A549. Methods: A549 cells were separately treated with blank, hGAG, DDP and hGAG combined with DDP (hGAG + DDP). The cell morphology in 4 groups was observed using light microscope. CCK8 assay was used to determine the cell viability. Flow cytometry by Hoechst 33258 and AnnexinV-FITC/PI staining was applied to detect cell apoptosis. Western blot was then used to detect the protein expression of Bax, Bcl-2, survivin and caspase-3. Results: After treatment for 24 h, the inhibitory rates of A549 cells in control, hGAG, DDP and hGAG + DDP groups were 0, (19.74±5.39)%, (42.01±2.57)% and (53.89±4.58)%, respectively. Moreover, after treatment for 48 h and 72 h, the inhibitory rates in each group were 0, (23.17±4.78)% and (29.17±4.21 )%, (54.00±7.64)% and (59.35±7.31)%, as well as (77.58±4.26)% and (79.94±4.58)%, respectively. The cell viability was significantly lower in drug treatment groups compared with those in control group at the same time point (P<0.05). Hochest 33258 staining showed that no obvious apoptotic cells were detected in the control group, while apoptotic cells were visible in hGAG, cisplatin and combination groups. Flow cytometry showed that cell apoptotic rates were (2.38±0.59)%, (12.59±4.22)%, (16.36±3.63)% and (44.60±5.45)% in the control, hGAG, DDP and hGAG + DDP groups, respectively. The cell apoptosis was significantly lower in drug treatment groups compared with those in control group at the same time point (P<0.05). Furthermore, western blot results showed that the expression of Bax and caspase-3 protein was increased (P<0.05), whereas Bcl-2 and survivin was decreased (P<0.05) in the hGAG+ DDP group compared with cisplatin alone (P<0.05). Conclusions: HGAG can inhibit the proliferation and promote the apoptosis of human lung adenocarcinoma A549 cells. Meanwhile, it can strengthen the chemosensitivity of A549 cells to DDP via up-regulation of Bax, caspase-3 and down-regulation of Bcl-2 and survivin.

Antitumor effect of miR-27b-3p on lung cancer cells via targeting Fzd7.

OBJECTIVE:   Lung cancer is the most common malignancy with the highest mortality rate among cancers. microRNAs (miRNAs) have been confirmed to be closely related to the physiological disorder, especially the tumor process. This study aimed to investigate the effect of miR-27b-3p on lung tumor cells. MATERIALS AND METHODS: The expressions of miR-27b-3p in lung tumors and adjacent non-tumors lung tissues were compared. We test the bonding effect of miR-27b-3p on the Fzd7 promoter, and miR-27b-3p effects on the Fzd7 expression in both NCI-H446 and A549 cells. Then, effects of miR-27b-3p and Fzd7 on these cells viability, survival and apoptosis were detected, respectively. In addition, the possible mechanism of miR-27b-3p affected these cells apoptosis was explored by analyzing the expression of apoptosis-related factors. RESULTS: We found that miR-27b-3p was low expressed in lung tumors compared to adjacent non-tumorous lung tissues. miR-27b-3p directly targeted Fzd7 promoter and negatively regulated Fzd7 expression. Fzd7 promoted NCI-H446 and A549 cells viability and survival, inhibited cells apoptosis. However, miR-27b-3p effects on these cells were quite the opposite to Fzd7. The expressions of apoptosis-related factors were associated positively with miR-27b-3p and showed a negative correlation with Fzd7 expression. CONCLUSIONS: The miR-27b-3p was lowly expressed in lung cancer tissues, and played the role of a tumor suppressor. It could promote cell apoptosis and suppress cancer cells viability and survival via down-regulating Fzd7. It suggested that miR-27b-3p might be a potential target for the prophylaxis and treatment of lung cancer.

[Application of principal component analysis in comprehensive indicator screening for pneumoconiosis in different regions].

Objective: To investigate the application of principal component analysis in comprehensive indicator screening for pneumoconiosis in different regions. Methods: A principal component analysis was performed for the data of 11 factors associated with the prediction of pneumoconiosis hazard and collected in the investigation on occupational health status conducted in 172 counties (districts) in Hebei, China. The degree of pneumoconiosis hazard in different regions was obtained and intuitively presented by GIS. Results: The eigenvalues of 5 principal components of pneumoconiosis were 4.103, 2.341, 0.981, 0.943, and 0.726, respectively, and the contribution values were 37.299%, 21.286%, 8.919%, 8.572%, and 6.596%, respectively. According to the comprehensive value of principal components, GIS Natural Breaks was used to divide the degree of pneumoconiosis hazard in 172 counties (districts) in Hebei into mild, moderate, and severe grades. Of all the counties, 46 had severe pneumoconiosis hazard, 69 had moderate pneumoconiosis hazard, and 57 had mild pneumoconiosis hazard, and the ranges of the score of principal components were 0.30-1.15, -0.24 to 0.27, and -0.69 to -0.25, respectively. Conclusion: Principal component analysis can optimize the comprehensive indicators for the evaluation of regional pneumoconiosis. The comprehensive score of principal components can quantify and intuitively show the degree of pneumoconiosis hazard in different regions. Tangshan, Chengde, Shijiazhuang, and Handan have the most severe pneumoconiosis hazard.

Parallel proteomic analysis in muscle-invasive bladder transitional cell carcinoma and cancer-related stroma.

To bring about improvements in cancer biology research and elucidate mechanism-based therapeutic targets, we studied the proteome expression profile of purified normal urothelial cells (cancer cells) and normal stromal cells (cancerous stromal cells). Based on the expression profile, biomarker discovery and the mechanisms of multi-step carcinogenesis were explored. We found that 1412/1403 unique proteins commonly appeared in 4 sets of paired cancer/normal tissue, and 1753 proteins were differentially expressed. Three hundred and forty-one proteins were repeatedly expressed in both cancer and cancer stromal cells; 358 proteins were repeatedly expressed in both normal urothelial and normal stromal cells. Among them, 186/203 proteins were specific repeat expressions in cancer/normal tissue and thought to play an important role in cancer-stroma interactions. Differential proteins were further analyzed using bioinformatic tools and compared with the published literature. GO enrichment/depletion analysis indicated that carcinogenesis involved all the biological processes and all the cellular components. Five hundred and sixty-eight differential proteins were located in the well-known biological Kyoto Encyclopedia of Genes and Genomes pathways, including metabolic pathways, ribosome spliceosome, and endocytosis. One hundred and thirty-nine of the 186 proteins that displayed specific repeat expressions in cancer tissue were located in the biological Kyoto Encyclopedia of Genes and Genomes pathways and are thought to be candidate biomarkers for targeted therapy.

Physiological consequences of the complete loss of phosphoryl-transfer proteins HPr and FPr of the phosphoenolpyruvate:sugar phosphotransferase system and analysis of fructose (fru) operon expression in Salmonella typhimurium.

Mutants of Salmonella typhimurium defective in the proteins of the fructose operon [fruB(MH)KA], the fructose repressor (fruR), the energy-coupling enzymes of the phosphoenolpyruvate:sugar phosphotransferase system (PTS) (ptsH and ptsI), and the proteins of cyclic AMP action (cya and crp) were analyzed for their effects on cellular physiological processes and expression of the fructose operon. The fru operon consists of three structural genes: fruB(MH), which encodes the enzyme IIIFru-modulator-FPr tridomain fusion protein of the PTS; fruK, which encodes fructose-1-phosphate kinase; and fruA, which encodes enzyme IIFru of the PTS. Among the mutants analyzed were Tn10 insertion mutants and lacZ transcriptional fusion mutants. It was found that whereas a fruR::Tn10 insertion mutant, several fruB(MH)::Mu dJ and fruK::Mu dJ fusion mutants, and several ptsHI deletion mutants expressed the fru operon and beta-galactosidase at high constitutive levels, ptsH point mutants and fruA::Mu dJ fusion mutants retained inducibility. Inclusion of the wild-type fru operon in trans did not restore fructose-inducible beta-galactosidase expression in the fru::Mu dJ fusion mutants. cya and crp mutants exhibited reduced basal activities of all fru regulon enzymes, but inducibility was not impaired. Surprisingly, fruB::Mu dJ crp or cya double mutants showed over 10-fold inducibility of the depressed beta-galactosidase activity upon addition of fructose, even though this activity in the fruB::Mu dJ fusion mutants that contained the wild-type cya and crp alleles was only slightly inducible. By contrast, beta-galactosidase activity in a fruK::Mu dJ fusion mutant, which was similarly depressed by introduction of a crp or cya mutation, remained constitutive. Other experiments indicated that sugar uptake via the PTS can utilize either FPr-P or HPr-P as the phosphoryl donor, but that FPr is preferred for fructose uptake whereas HPr is preferred for uptake of the other sugars. Double mutants lacking both proteins were negative for the utilization of all sugar substrates of the PTS, were negative for the utilization of several gluconeogenic carbon sources, exhibited greatly reduced adenylate cyclase activity, and were largely nonmotile. These phenotypic properties are more extreme than those observed for tight ptsH and ptsI mutants, including mutants deleted for these genes. A biochemical explanation for this fact is proposed.