Humans ; Diabetic Nephropathies/pathology* ; Kidney/pathology* ; Biopsy ; Diabetes Mellitus, Type 2/pathology* ; Retrospective Studies ; Glomerular Filtration Rate ; Disease Progression

Purpose: The role of vacuolar protein sorting 34 (Vps34), an indispensable protein required for cell vesicular trafficking, in the biological behavior of hepatocellular carcinoma (HCC) has yet to be studied. Materials and Methods: In the present study, the expression of Vps34 in HCC and the effect of Vps34 on HCC cell invasion was detected both in vivo and in vitro. Furthermore, by modulating the RILP and Rab11, which regulate juxtanuclear lysosome aggregation and recycling endosome respectively, the underlying mechanism was investigated. Results: Vps34 was significantly decreased in HCC and negatively correlated with the HCC invasiveness both in vivo and in vitro. Moreover, Vps34 could promote lysosomal juxtanuclear accumulation, reduce the invasive ability of HCC cells via the Rab7-RILP pathway. In addition, the deficiency of Vps34 in HCC cells affected the endosome-lysosome system, resulting in enhanced Rab11 mediated endocytic recycling of cell surface receptor and increased invasion of HCC cells. Conclusion Our study reveals that Vps34 acts as an invasion suppressor in HCC cells, and more importantly, the endosome-lysosome trafficking regulated by Vps34 has the potential to become a target pathway in HCC treatment.

ERK pathway regulated the programmed death ligand-1 (PD-L1) expression which was linked to the response of programmed death-1 (PD-1)/PD-L1 blockade therapy. So it is deducible that ERK inhibitor could enhance the efficacy of PD-1 inhibitor in cancer immunotherapy. In this study, PD0325901, an oral potent ERK inhibitor, strongly enhanced the efficacy of PD-1 antibody

Objective:To comparatively evaluate the scan time and the accuracy of maxillary full-arch scans using four intraoral scanners (IOS) on conditions of the intraoral head-simulator and the hand-held model, and to evaluate the influence of different scanning conditions on digital scan.Methods:A upper dental arch model with melamine-formaldehyde resin teeth and silica gel gingiva that could be fixed on a head simulator was scanned with an optical scanner (ATOS Core) in order to obtain the standard tessellation language dataset as reference. Intraoral scans were performed on the model fixed on the head simulator by three researchers with four IOS [A: TRIOS 3; B: CS 3600; C: CEREC Omnicam; D: iTero]. For each scanner and each researcher, six scans were performed, to obtain the datasets as the head simulator group. And another six scans with each of the four intraoral scanners were performed by each researcher on the hand-held model to obtain the STL datasets as the hand-held group. The scan time were recorded for each scan. In the Geomagic Wrap software, the digital models were trimmed with only the teeth information retained and supreimposed by best fit alignment function and compared to obtain the root mean square (RMS) values of the discrepancies by three-dimensional compare function. The test datasets of each group were compared with the reference dataset for trueness. The six test scanning datasets with the same scanner of the same researcher were cross compared for precision. Mann Whitney U test was used to statistically analyze the difference values of the scan time, trueness and precision of the same intraoral scanner between head simulator group and hand-held group. Results:Compared to the hand-held group, the scan time of A [142(82) s] and D [119(52) s], which two IOS both with handle, were longer in head simulator group [A: 98(28) s; D: 85(22) s] ( P<0.01). However there were no significant differences between the two groups for scan time of IOS B and C ( P>0.05). For full-arch scan accuracy (trueness and precision), there were no significant differences between the two groups of IOS A and B ( P>0.05), while the trueness of C ( P<0.05) and the precision of D ( P<0.01) were better in head simulator group [C: 112(38) μm; D: 43(13) μm] compared to hand-held group [C: 135(47) μm; D: 53(18) μm]. However, there were no significant differences for the precision of C ( P>0.05) and the trueness of D ( P>0.05). Conclusions:The scan time and the accuracy of full-arch digital scans with different IOS may be effected by the scan conditions. For in vitro study of intraoral scanning, head-simulator can simulate the intraoral environment of the real patient to some extent. Meanwhile, the position of the dentist and the patient, and also the limited intraoral space during intraoral scanning are also simulated.

Objective:To comparatively evaluate the accuracy and the scan time of three full-arch scan strategies on the head-simulator, to explore a full-arch scan strategy with better clinical operability and high accuracy.Methods:A cross-controlled study design was used. A model with melamine-formaldehyde resin teeth and silica gel gingiva of an upper dental arch which can be fixed on a head simulator was scanned with an optical scanner (ATOS Core) in order to obtain the standard tessellation language (STL) dataset as reference. Intraoral scans were performed on the model fixed on the head simulator with four intraoral scanners (IOS) [A (TRIOS 3), B (CS 3600), C (CEREC Omnicam), D (iTero)]. The STL datasets were obtained from each of the four different IOS systems by using three scan strategies (scan strategies 1, 2 and 3 were composed of 10, 5 and 7 paths respectively) all by one attending doctor with 3 years of intraoral scanning experience. For each scanner and each scan strategy, nine scans were acquired. And the scan time was recorded for each scan. Following the scan strategy, the scan path was completed to obtain a full-arch digital model, and the scan time was recorded as full-arch scan time. Complementary scans were performed to fill the missing image, and this scan time was recorded as complementary scan time. The total scan time was obtained by adding full-arch scan time and complementary scan time. Through the Geomagic Wrap software, the three-dimensional (3D) models were overlaid by best fit alignment function and compared to obtain the root mean square values of the discrepancies by 3D compare function. The intraoral scanning datasets were compared with the reference for trueness. The nine intraoral scanning datasets were cross compared with same scan strategy and same intraoral scanner for precision.Results:There were no significant differences among the three scan strategies for trueness ( P>0.05), while the differences among the three scan strategies for precision were affected by difference IOSs ( P<0.05), and only scan strategy 3 showed the highest precision with all the four IOS. The full-arch scan time of scan strategies 1, 2 and 3 were (130±24), (72±17) and (90±19) s respectively ( P<0.05). For complementary scan time, scan strategy 2 [(50±24) s] took longer time than scan strategy 1 [(26±18) s] and scan strategy [(25±21) s] ( P<0.05), while no significant differences between the latter two ( P>0.05). For total scan time, scan strategy 1 [(156±31) s] took longer time than scan strategy 2 [(122±30) s ] and scan strategy 3 [(115±29) s ] ( P<0.05), while no significant differences between the latter two ( P>0.05). Conclusions:Full-arch scanning on the head-simulator with scan strategy 3 which can obtain scanning datasets with high accuracy, was more convenient to operate and took shorter scan time, and is generally suitable for intraoral scanners commonly used in clinic.

Objective:To evaluate the expression of LEF1 protein in lymphoblastic lymphoma/acute lymphoblastic leukemia (LBL/ALL) and small B-cell lymphomas, and its value in pathologic diagnosis and differential diagnosis of LBL/ALL.Methods:53 cases of LBL/ALL were collected at shanghai Tongji Hospital from January 2012 to December 2019. The protein expression of LEF1 and TdT was detected by immunohistochemistry in 53 paraffin-embedded tissue samples of LBL/ALL. The specificity and sensitivity of LEF1 and TdT in the diagnosis of LBL/ALL were compared. The expression of LEF1 protein in 77 cases of small B-cell lymphomas including chronic lymphocytic leukemia/small lymphoid lymphoma (CLL/SLL), follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma and Waldenstrom′s macroglobulinemia/lymphoplasmacytic lymphoma was studied. The correlation between LEF1 expression and overall survival (OS) and progression-free survival (PFS) was performed by univariate analysis.Results:The expression of LEF1 in LBL/ALL was 100% (53/53), the median value was 90%; the expression of TdT was 84.9% (T-LBL/ALL 78.1%, B-LBL/ALL 95.2%), the median value was 80%; the expression rate and median value of LEF1 and TdT were significantly different ( P=0.008 and 0.001 respectively). The expression of LEF1 in CLL/SLL was 14/18, the median value was 45%; LEF1 was not expressed in follicular lymphoma (0/16), mantle cell lymphoma (0/16), marginal zone lymphoma (0/19), and Waldenstrom′s macroglobulinemia/lymphoplasmacytic lymphoma (0/8). LEF1 expression was significantly different between B-LBL/ALL and small B-cell lymphomas. The median follow-up time of LBL/ALL cases in this group was 16 months. There was no statistical difference between LEF1 expression and the OS and PFS in LBL/ALL patients. Conclusions:Immunohistochemical staining of LEF1 has high sensitivity and good specificity in the diagnosis of LBL/ALL, and its combination with TdT can improve the diagnostic rate of LBL/ALL.

Objective: To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison. Methods: Peking University People’s Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated. Results: ①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories’ results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH. Conclusion The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.

PURPOSE: Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone administered every 3 weeks (R-CHOP-21) is the standard care for diffuse large B-cell lymphoma (DLBCL). It is unknown whether the dose-dense R-CHOP (R-CHOP-14) could improve the outcome of the disease in Asian population. MATERIALS AND METHODS: Newly diagnosed DLBCL patients were centrally, randomly assigned (1:1) to receive R-CHOP-14 or R-CHOP-21. R-CHOP-14 was administered every 2 weeks, and R-CHOP-21 was administered every 3 weeks. Primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), progression-free survival (PFS), response rate and toxicities. RESULTS: Seven hundred and two patients were randomly assigned to receive R-CHOP-14 (n=349) or R-CHOP-21 (n=353). With a median follow-up of 45.6 months, the two groups did not differ significantly in 3-year DFS (79.6% for R-CHOP-14 vs. 83.2% for R-CHOP-21, p=0.311), 3-year OS (77.5% for R-CHOP-14 vs. 77.6% for R-CHOP-21, p=0.903), or 3-year PFS (63.2% for R-CHOP-14 vs. 66.1% for R-CHOP-21, p=0.447). Patients with an International Prognostic Index (IPI) score ≥ 2 had a poorer prognosis compared to those with an IPI score < 2. Grade 3/4 hematologic and non-hematologic toxicities were manageable and similar between R-CHOP-14 and R-CHOP-21. CONCLUSION: R-CHOP-14 did not improve the outcome of DLBCL compared to R-CHOP-21 in Asian population. With manageable and similar toxicities, both of the two regimens were suitable for Asian DLBCL patients. For high-risk patients with IPI ≥ 2, new combination regimens based on R-CHOP deserve further investigation to improve efficacy.
Asian Continental Ancestry Group ; B-Lymphocytes ; Cyclophosphamide ; Disease-Free Survival ; Doxorubicin ; Follow-Up Studies ; Humans ; Lymphoma, B-Cell ; Prednisone ; Prognosis ; Rituximab ; Vincristine

Objective: o investigate the features of pathogenic bacteria for community-acquired bloodstream infection due to Gram-negative bacilli in patients with liver cirrhosis and optimal therapeutic strategy. Methods: A retrospective analysis was performed for the clinical data of patients with liver cirrhosis who were admitted to 302 Hospital of PLA due to community-acquired bloodstream infection from January 2010 to December 2015, and a statistical analysis was performed for their clinical features, pathogenic bacteria, and results of drug sensitivity test. The Pearson chi-square test was used for comparison of rates, and the Wilcoxon rank sum test was used for comparison of ranked data. Results: A total of 240 patients (including 178 male patients) with liver cirrhosis caused by various reasons were enrolled, with a mean age of 51.7 ± 11.1 years, an overall clinical remission rate of 80.42%, and an ineffective/mortality rate of 19.58%. The patients who used sensitive antibiotics within 12 hours after the onset of community-acquired bloodstream infection achieved a significantly higher improvement rate than those who used such drugs at more than 12 hours after onset (88.2% vs 58.1%, P < 0.001). The improvement rate achieved by the application of sensitive antibiotics at more than 12 hours after onset decreased with the increase in the Child-Pugh grade (P < 0.05). A total of 245 strains of Gram-negative bacilli were isolated, among which the six most common ones were 135 strains of Escherichia coli (55.1%), 62 strains of Klebsiella pneumoniae (25.3%), 16 strains of Aeromonas (6.5%), 4 strains of non-typhoidal Salmonella (1.6%), 3 strains of Enterobacter cloacae (1.2%), and 2 strains of Acinetobacter baumannii (0.8%). These Gram-negative bacilli had the highest sensitivity to meropenem (98.5%), followed by imipenem (97.9%), amikacin (97.5%), piperacillin/tazobactam (94.7%), cefmetazole (93.7%), and cefoperazone/sulbactam (93%). Different bacteria had different sensitivities to antibiotics. Conclusion Once community-acquired bloodstream infection occurs in patients with liver cirrhosis, highly sensitive antibiotics should be used as early as possible. Cefoperazone/sulbactam, piperacillin/tazobactam, imipenem, and meropenem can be used as first-line empirical antibiotics, and drug combination should be considered when necessary.

Objective To investigate recurrent spontaneous abortion patients received bends the clinical application effect of nursing intervention during progesterone treatment. Methods Two patients with recurrent spontaneous abortion group were treated with progesterone treatment, the control group in the conventional nursing service only provides flexor progesterone treatment on the basis of comprehensive nursing service study group progesterone treatment on the basis of routine the combination of nursing and nursing intervention in the 2 groups of patients with recurrent spontaneous abortion. The success rate of pregnancy were recorded, the rate of abortion, the data will be given the statistical analysis (using SPSS software) after the conclusion. Results The study group of patients with recurrent spontaneous abortion pregnancy success rate (95.45%) and control group (90.91%) there is no significant difference between the study group of patients with recurrent spontaneous abortion abortion rate (6.82%) was significantly lower than the control group (34.09%), there was significant difference between the groups, P<0.05. Conclusion Recurrence During the treatment of flexor progesterone abortion were given routine nursing and nursing intervention combined with the comprehensive clinical nursing service can obtain ideal success rate of pregnancy, to reduce the rate of abortion is also of positive significance, is conducive to the protection of patients' quality of life, physical and mental health.