Objective:To conduct a nationwide physician survey to better understand clinicians’ disease awareness, treatment patterns, and experience of Waldenstr?m macroglobulinemia (WM) in China.Methods:This cross-sectional study was conducted from February 2022 to July 2022 by recruiting clinicians with WM treatment experience from hematology, hematology-oncology, and oncology departments throughout China. Quantitative surveys were designed based on the qualitative interviews.Results:The study included 415 clinicians from 219 hospitals spread across thirty-three cities and twenty-two provinces. As for diagnosis, the laboratory tests prescribed by physicians for suspected WM patients were relatively consistent (92% -99% recommendation for laboratory, 79% -95% recommendation for pathology, 96% recommendation for gene testing, and 63% -83% recommendation for imaging examination). However, from a physician's perspective, there was 22% misdiagnosis occurred in clinical practice. The rate of misdiagnosis was higher in lower-level hospitals than in tertiary grade A hospitals (29% vs 21%, P<0.001). The main reasons for misdiagnosis were that WM was easily confused with other diseases, and physicians lacked the necessary knowledge to make an accurate diagnosis. In terms of gene testing in clinical practice, 96% of participating physicians believed that WM patients would require gene testing for MYD88 and CXCR4 mutations because the results of gene testing would aid in confirming diagnosis and treatment options. In terms of treatment, 55% of physicians thought that the most important goal was to achieve remission, while 54% and 51% of physicians wanted to improve laboratory and/or examination results and extend overall survival time, respectively. Among patients with treatment indications, physicians estimated that approximately 21% of them refused to receive treatment, mainly owing to a lack of affordable care and disease awareness. When selecting the most appropriate treatment regimens, physicians would consider patient affordability (63% ), comorbidity (61% ), and risk level (54% ). Regimens containing Bruton tyrosine kinase inhibitor (BTKi) were most widely recommended for both treatment-na?ve and relapsed/refractory patients (94% for all patients, 95% for treatment-na?ve patients, and 75% for relapsed/refractory patients), and most physicians recommended Ibrutinib (84% ). For those patients who received treatment, physicians reported that approximately 23% of patients did not comply with the treatment regimen due to a lack of affordability and disease awareness. Furthermore, 66% of physicians believe that in the future, increasing disease awareness and improving diagnosis rates is critical. Conclusions:This study is the first national physician survey of WM conducted in China. It systematically describes the issues that exist in WM diagnosis and treatment in China, such as a high rate of misdiagnosis, limited access to gene testing and new drugs, and poor patient adherence to treatment. Chinese doctors believe that improving doctors’ and patients’ understanding of WM is one of the most urgent issues that must be addressed right now.

Objective:To investigate the correlation between bladder mucosal smoothness (BMS) and early urinary continence recovery following laparoscopic radical prostatectomy (LRP).Methods:A retrospective analysis was conducted on the clinical data of 192 prostate cancer patients who underwent LRP at Peking University Third Hospital between January 2016 and March 2020. The patients' average age was (69.1±8.0) years old, and the median pre-biopsy PSA level was 12.23 (7.45, 20.36) ng/ml. There were 69 patients (35.9%) with a Gleason score <7 and 123 patients (64.1%) with a Gleason score ≥7. Clinical staging showed that 92 patients (47.9%) were in stage T 1/T 2, and 100 patients (52.1%) were in stage T 3. All patients underwent MRI before prostate biopsy. The preoperative MRI measured the prostate volume (PV) as 35.4 (26.3, 51.1) ml, and membranous urethral length (MUL) as (13.9±3.5) mm. The intravesical prostatic protrusion length (IPPL) was <5 mm in 128 patients (66.7%) and ≥5 mm in 64 patients (33.3%). All patients completed MRI examination before biopsy, BMS was defined into four grades according to MRI: grade 0, the bladder mucosa is completely smooth; grade 1, a small amount of unevenness and bumps can be seen in the bladder mucosa; grade 2, fissures can be seen in the bladder mucosa, less than half of the bladder wall, or bladder diverticulum; grade 3, the bladder fissure exceeds half of the bladder wall, or fissure progresses to a small loss of muscularis. In this study, there were 63 patients (32.8%) with grade 0, 95 patients (49.5%) with grade 1, and 34 patients (17.7%) with grade 2-3. Postoperatively, patients were followed up monthly from the first month onwards to assess urinary continence recovery, defined as not requiring pads throughout the day. Logistic multivariate regression analysis was used to identify risk factors affecting early postoperative urinary continence recovery, and log-rank test was used to compare postoperative urinary continence recovery curves among different groups. Results:All surgeries were successfully completed. The complete urinary continence rates at 1, 3, 6, and 12 months postoperatively were 40.1% (77/192), 57.8% (111/192), 71.9% (138/192), and 90.1% (173/192), respectively.In the univariate analysis of urinary incontinence, the proportion of urinary incontinence was lower in patients with PV <40 ml than that in patients with PV ≥40 ml [33.0% (38/115) vs. 55.8% (43/77), P<0.05]. The proportion of urinary incontinence in patients with maximum urethral length (MUL) <14 mm was higher than that in patients with MUL ≥14 mm [75.7% (56/74) vs. 21.2% (25/118), P<0.05]. The proportion of urinary incontinence in patients with the interpubic prostate length (IPPL) <5 mm was lower than that in patients with IPPL ≥5 mm [26.6% (34/128) vs. 73.4% (47/64), P<0.05]. The proportion of urinary incontinence was lower in the group with a BMS of 0 compared to those with BMS of 1 and BMS of 2-3 [23.8% (15/63) vs. 47.4% (45/95) vs. 61.8% (21/34), P<0.05]. These results indicated that the differences in urinary incontinence proportions across these indicators are statistically significant. Multivariate analysis indicated that MUL, IPPL, and BMS were independent risk factors for early postoperative urinary incontinence(all P<0.05). The log-rank test demonstrated that differences in postoperative urinary continence recovery among groups with different PV ( P<0.05), MUL, IPPL, and BMS were all statistically significant(all P<0.05). Conclusions:Higher BMS grades are an independent risk factor for early postoperative urinary incontinence. Preoperative MUL, IPPL, PV, and BMS are correlated with urinary continence recovery after LRP. These findings require further validation in larger clinical studies.

Objective To explore the pathogenic roles of miR-21, estrogen (E2), and estrogen receptor (ER) in adenomyosis. Methods We examined the expression levels of miR-21 in specimens of adenomyotic tissue and benign cervical lesions using qRT-PCR. In primary cultures of cells isolated from the adenomyosis lesions, the effect of ICI82780 (an ER inhibitor) on miR-21 expression levels prior to E2 activation or after E2 deprivation were examined with qRT-PCR. We further assessed the effects of a miR-21 mimic or an inhibitor on proliferation, apoptosis, migration and autophagy of the cells. Results The expression level of miR-21 was significantly higher in adenomyosis tissues than in normal myometrium (P<0.05). In the cells isolated from adenomyosis lesions, miR-21 expression level was significantly higher in E2 activation group than in ER inhibition+E2 activation group and the control group (P<0.05);miR-21 expression level was significantly lower in cells in E2 deprivation+ER inhibition group than in E2 deprivation group and the control group (P<0.05). The adenomyosis cells transfected with miR-21 inhibitor showed inhibited proliferation and migration, expansion of mitochondrial endoplasmic reticulum, increased lysosomes, presence of autophagosomes, and increased cell apoptosis, while transfection of the cells with the miR-21 mimic produced the opposite effects. Conclusion MiR-21 plays an important role in promoting proliferation, migration, and anti-apoptosis in adenomyosis cells by altering the cell ultrastructure, which may contribute to early pathogenesis of the disease. In addition to binding with E2, ER can also regulate miR-21 through other pathways to participate in the pathogenesis of adenomyosis, thus having a stronger regulatory effect on miR-21 than E2.

Objective To explore the pathogenic roles of miR-21, estrogen (E2), and estrogen receptor (ER) in adenomyosis. Methods We examined the expression levels of miR-21 in specimens of adenomyotic tissue and benign cervical lesions using qRT-PCR. In primary cultures of cells isolated from the adenomyosis lesions, the effect of ICI82780 (an ER inhibitor) on miR-21 expression levels prior to E2 activation or after E2 deprivation were examined with qRT-PCR. We further assessed the effects of a miR-21 mimic or an inhibitor on proliferation, apoptosis, migration and autophagy of the cells. Results The expression level of miR-21 was significantly higher in adenomyosis tissues than in normal myometrium (P<0.05). In the cells isolated from adenomyosis lesions, miR-21 expression level was significantly higher in E2 activation group than in ER inhibition+E2 activation group and the control group (P<0.05);miR-21 expression level was significantly lower in cells in E2 deprivation+ER inhibition group than in E2 deprivation group and the control group (P<0.05). The adenomyosis cells transfected with miR-21 inhibitor showed inhibited proliferation and migration, expansion of mitochondrial endoplasmic reticulum, increased lysosomes, presence of autophagosomes, and increased cell apoptosis, while transfection of the cells with the miR-21 mimic produced the opposite effects. Conclusion MiR-21 plays an important role in promoting proliferation, migration, and anti-apoptosis in adenomyosis cells by altering the cell ultrastructure, which may contribute to early pathogenesis of the disease. In addition to binding with E2, ER can also regulate miR-21 through other pathways to participate in the pathogenesis of adenomyosis, thus having a stronger regulatory effect on miR-21 than E2.

Objective:To investigate the correlation between bladder mucosal smoothness (BMS) and early urinary continence recovery following laparoscopic radical prostatectomy (LRP).Methods:A retrospective analysis was conducted on the clinical data of 192 prostate cancer patients who underwent LRP at Peking University Third Hospital between January 2016 and March 2020. The patients' average age was (69.1±8.0) years old, and the median pre-biopsy PSA level was 12.23 (7.45, 20.36) ng/ml. There were 69 patients (35.9%) with a Gleason score <7 and 123 patients (64.1%) with a Gleason score ≥7. Clinical staging showed that 92 patients (47.9%) were in stage T 1/T 2, and 100 patients (52.1%) were in stage T 3. All patients underwent MRI before prostate biopsy. The preoperative MRI measured the prostate volume (PV) as 35.4 (26.3, 51.1) ml, and membranous urethral length (MUL) as (13.9±3.5) mm. The intravesical prostatic protrusion length (IPPL) was <5 mm in 128 patients (66.7%) and ≥5 mm in 64 patients (33.3%). All patients completed MRI examination before biopsy, BMS was defined into four grades according to MRI: grade 0, the bladder mucosa is completely smooth; grade 1, a small amount of unevenness and bumps can be seen in the bladder mucosa; grade 2, fissures can be seen in the bladder mucosa, less than half of the bladder wall, or bladder diverticulum; grade 3, the bladder fissure exceeds half of the bladder wall, or fissure progresses to a small loss of muscularis. In this study, there were 63 patients (32.8%) with grade 0, 95 patients (49.5%) with grade 1, and 34 patients (17.7%) with grade 2-3. Postoperatively, patients were followed up monthly from the first month onwards to assess urinary continence recovery, defined as not requiring pads throughout the day. Logistic multivariate regression analysis was used to identify risk factors affecting early postoperative urinary continence recovery, and log-rank test was used to compare postoperative urinary continence recovery curves among different groups. Results:All surgeries were successfully completed. The complete urinary continence rates at 1, 3, 6, and 12 months postoperatively were 40.1% (77/192), 57.8% (111/192), 71.9% (138/192), and 90.1% (173/192), respectively.In the univariate analysis of urinary incontinence, the proportion of urinary incontinence was lower in patients with PV <40 ml than that in patients with PV ≥40 ml [33.0% (38/115) vs. 55.8% (43/77), P<0.05]. The proportion of urinary incontinence in patients with maximum urethral length (MUL) <14 mm was higher than that in patients with MUL ≥14 mm [75.7% (56/74) vs. 21.2% (25/118), P<0.05]. The proportion of urinary incontinence in patients with the interpubic prostate length (IPPL) <5 mm was lower than that in patients with IPPL ≥5 mm [26.6% (34/128) vs. 73.4% (47/64), P<0.05]. The proportion of urinary incontinence was lower in the group with a BMS of 0 compared to those with BMS of 1 and BMS of 2-3 [23.8% (15/63) vs. 47.4% (45/95) vs. 61.8% (21/34), P<0.05]. These results indicated that the differences in urinary incontinence proportions across these indicators are statistically significant. Multivariate analysis indicated that MUL, IPPL, and BMS were independent risk factors for early postoperative urinary incontinence(all P<0.05). The log-rank test demonstrated that differences in postoperative urinary continence recovery among groups with different PV ( P<0.05), MUL, IPPL, and BMS were all statistically significant(all P<0.05). Conclusions:Higher BMS grades are an independent risk factor for early postoperative urinary incontinence. Preoperative MUL, IPPL, PV, and BMS are correlated with urinary continence recovery after LRP. These findings require further validation in larger clinical studies.

Objective:To investigate the risk factors and missed diagnosis of intraductal carcinoma of prostate (IDC-P) in patients with metastatic prostate cancer.Methods:The preoperative PSA, prostate MRI, bone scans and lung CT of all patients who underwent prostate biopsy in Department of Urology, Xiangya Hospital, Central South University from January 2018 to July 2020 were reviewed. A total of 261 patients with high suspicion of metastatic prostate cancer were screened for inclusion. Two full-time senior pathologists of urogenital tumors in Xiangya Hospital independently reviewed their pathological sections and detected IDC-P according to the 2016 WHO tumor classification. Diagnostic criteria are defined as malignant epithelial cells filling large acini and prostatic ducts, with preservation of basal cells and solid or dense cribriform pattern/loose cribriform or micropapillary pattern with either marked nuclear atypia or non-focal comedonecrosis.Results:The detection rate of IDC-P was 29.12%(76/261), while the actual reporting rate was only 9.96%(26/261). The results of subgroup analysis including age, PSA level, Gleason score as well as different metastatic sites showed that detection rate of IDC-P was 33.69% in the PSA≥50 ng/ml subgroup, much higher than 17.57% in the PSA <50 ng/ml subgroup ( P=0.0039); And it was 32.33% in the Gleason score ≥ 8 subgroup, much higher than 3.45% in the Gleason score < 8 subgroup ( P<0.01). It was not significantly different in different age subgroups as well as different metastatic site subgroups. These data suggest that PSA ≥ 50 ng/ml as well as Gleason score ≥ 8 may be risk factors of IDC-P.157 samples were stained by immunohistochemistry. The detection rates of IDC-P were 84.21% (16/19) in P63 (+ ) samples, 36.00% (9/25) in ERG (+ ) samples. There were 3 samples with both P63 (+ ) and ERG (+ ), all of which had IDC-P. Conclusions:There is misdiagnosis of IDC-P on prostate needle biopsy in patients with metastatic prostate cancer currently. PSA ≥ 50 ng/ml and Gleason score ≥ 8 are risk factors of IDC-P. Thus, attention should be paid to the possibility of IDC-P in such patients. When the diagnosis is difficult, immunohistochemical staining for ERG and P63 is helpful in IDC-P determination.

Objective:To investigate the clinical, genetic, and clonality related aspects of individuals with Richter transformation (RT) .Methods:From January 2019 to December 2021, 18 RT patients with diagnoses at the First Affiliated Hospital of Nanjing Medical University (Pukou CLL center) were retrospectively examined. The immunoglobin heavy variable (IGHV) gene usage and IGHV-D-J rearrangement pattern of diagnosed CLL/SLL and transformed diffuse large B-cell lymphoma (DLBCL) were compared to determine the clonality relatedness. To investigate the risk factors of RT, Clinical and laboratory data from patients with newly diagnosed CLL/SLL and transformed DLBCL were gathered.Results:The median age of RT was 56.5 (41-75) years old. 17 patients transformed to DLBCL and 1 transformed to Hodgkin lymphoma (HL) . Of 17 individuals who had DLBCL transformation, 15 had CLL/SLL-related clonality and 2 had unrelated clonality. Next-generation sequencing (NGS) analysis of 11 paired initially diagnosed treatment-naive CLL/SLL and RT DLBCL found that EGR2、TP53 and NOTCH1 were among the most frequently mutated genes both in treatment-naive CLL/SLL and in RT DLBCL. In several cases, specific mutations were gained or lost throughout RT, indicating clonal evolution. Among 10 patients before exposure to BTK inhibitors before RT, four patients acquired BTK mutation. The aforementioned mutations should be considered high-risk variables for transformation; in addition, TP53 and EGR2 mutations could be linked to a poor prognosis following RT in patients receiving a cocktail of new medicines.Conclusion:Most RT DLBCL patients in our center are clonality related (15/17, 88.2% ) and we recommend all qualified centers to evaluate clonality relatedness of RT DLBCL patients. There was some variability in the mutational landscape between DLBCL that had undergone a transformation and initially diagnosed, treatment-naive CLL/SLL. The underlying molecular mechanism of RT needs more research.

ObjectiveTo explore the activating effects of ten important effective components in seven medicinal and edible substances on human pregnane X receptor （PXR）， including Glycyrrhizae Radix et Rhizoma （liquiritin and glycyrrhizic acid）， Houttuyniae Herba （quercetin and houttuyfonate）， Prunellae Spica （rosmarinic acid）， Cassiae Semen （aurantio-obtusin）， Poria （pachymic acid）， Lilii Bulbus （Lilium brownii saponin and colchicine）， and Lycii Fructus （Lycium barbarum polysaccharide） and screen potentially toxic components. MethodCell counting kit-8 （CCK-8） assay was used to investigate the cytotoxic effect of liquiritin， glycyrrhizic acid， quercetin， houttuyfonate， rosmarinic acid， pachymic acid， aurantio-obtusin， and colchicine （10， 20， and 50 μmol·L^-1）， and L. brownii saponin and L. barbarum polysaccharide （10， 20， and 50 mg·L^-1） on normal human hepatocyte cell line （L02）. The release of lactate dehydrogenase （LDH） in L02 cells after drug treatments was detected by the biochemical analyzer. The apoptosis induced by ten effective components was explored by Hoechst 33342 staining. The secreted luciferase reporter system was used to co-transfect the PXR expression vector and reporter gene vector containing cytochrome P450 3A4 （CYP3A4） transcriptional regulatory region into L02 cells， with 10 μmol·L^-1 rifampicin （RIF） as a positive control. After treated with liquiritin， glycyrrhizic acid， quercetin， houttuyfonate， rosmarinic acid， aurantio-obtusin， pachymic acid， and colchicine （5， 10， and 20 μmol·L^-1） and L. brownii saponin and L. barbarum polysaccharide （5， 10， and 20 mg·L^-1） for 24 h， the cells were tested for secreted luciferase activity. ResultCompared with the control group， colchicine， L. brownii saponin， and quercetin decreased the cell viability （P<0.05， P<0.01）. Compared with the control group， quercetin， rosmarinic acid， glycyrrhizic acid， colchicine， aurantio-obtusin， and pachymic acid increased the release rate of LDH in L02 cells （P<0.05， P<0.01）. The proportion of hyperchromatic nuclei increased gradually after rosmarinic acid， liquiritin， and L. barbarum polysaccharide treatments as compared with the control group （P<0.05， P<0.01）. In terms of co-transfection of pcDNA3.1-PXR and pGLuc-CYP3A4 into L02 cells， compared with the control group， aurantio-obtusin and pachymic acid showed activating effects on PXR （P<0.05）， whereas liquiritin and glycyrrhizic acid showed inhibitory effects （P<0.05）. ConclusionThe findings suggest that when medicinal and edible substances are taken for a long time， attention should be paid to their influence on drug-metabolizing enzymes and possible interactions， so as to improve their safety.

Objective:To evaluate the feasibility of high concentrated contrast media combined with monochromatic images to improve image quality with double low scanning in dual-layer spectral coronary CT angiography.Methods:Fifty-six patients with suspected coronary artery disease were enrolled and randomly separated into two groups. All patients were scanned at 120 kVp in step-and-shoot mode using a dual-layer detector CT (IQon spectral CT). Patients were either injected with 18 ml high concentration contrast medium(400 mgl/ml) at 2 ml/s (group A) or 45 ml contrast medium (370 mgl/ml) at 4 ml/s (group B). Forty to 80 keV monoenergetic images with 10 keV increment and conventional image (group A2) were reconstructed for group A, conventional poly-energetic image was reconstructed for group B. Region of interest was placed on aorta root (AO), middle segment of left anterior descending (LAD), left circumflex (LCX) and right coronary artery (RCA) to measure the attenuation and noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Image quality was assessed by two reviewers independently with a 4-point scale on image quality (1-undiagnostic,4-excellent). The objective and subjective image evaluation were compared using the Kruskal-Wallis test. The Steel Dwass was used for multiple comparisons between monoenergetic images in Group A and conventional images in Group B, after the Kruskal-Wallis test.Results:There were significant differences among the attenuation, noise, SNR and CNR of group B, group A2, and monoenergetic images(all P<0.001).The CT value in the aortic root was significantly higher at 40-50 keV monoenergetic images than that in group B(all P<0.05), and similarly, the CT value in LAD,LCX and RCA at 40 keV were superior than that in group B(all P<0.001). There was no significant difference in the noise of the aortic root among 40 keV image, group A2 and group B(all P>0.05),while the noise in the 50-80 keV monoenergetic images were significantly lower than that in Group B(all P<0.001). The SNR and CNR in the aortic root were significantly higher at 40-60 keV monoenergetic images than that in group B(all P<0.001).The SNR in LAD and RCA at 40，50 keV and the CNR in LAD and RCA at 40-60 keV were higher than that in group B(all P<0.01).The SNR at 40-60 keV and CNR at 40-70 keV in LCX were superior than that in group B(all P<0.05). There were significant differences among the subjective image quality score of group B, group A2, and monoenergetic images(all P<0.001).The subjective image quality score of 40，50 keV images were not significantly different from that in group B (all P>0.05),while the score in 60-80 keV image and group A2 were lower than that of Group B(all P<0.001). Conclusion:40，50 keV low monochromatic images derived from dual-layer spectral detect CT combined with high concentrated contrast media can provide comparable or superior image quality with double low scanning in CCTA study.

OBJECTIVE: To investigate the change of pulmonary ventilation function in patients with simple type and complex type pneumoconiosis based on high resolution computed tomography(HRCT). METHODS: A total of 188 male patients with pneumoconiosis were selected as the study subjects by judgment sampling method. Patients were divided them into simple type group(104 cases) and complex type group(84 cases) according to their chest HRCT findings. Another 80 healthy men who have no dust and other occupational hazard exposure were selected as the control group. The lung function tests were performed in patients in these three groups. RESULTS: The indexes of pulmonary function including vital capacity, forced vital capacity(FVC), forced expiratory volume in one second(FEV_1), FEV_1/FVC%, peak expiratory flow, forced expiratory flow at 25% of FVC exhaled, forced expiratory flow at 50% of FVC exhaled, forced expiratory flow at 75% of FVC exhaled and forced expiratory flow at 25% to 75% of vital capacity were lower in patients with pneumoconiosis of simple type and complex type groups than that in the control group(all P<0.01). The above indexes in the complex type group were lower than that in the simple type group(all P<0.01). The detection rate of pulmonary ventilation dysfunction in patients with pneumoconiosis was 64.9%. Among them, the detection rate of obstructive, restrictive and mixed ventilation dysfunction were 33.5%, 5.3% and 26.1%, respectively. The detection rates of pulmonary ventilation dysfunction and mixed ventilation dysfunction were higher in complex type group than that in simple type group(82.1% vs 51.0%, 41.7% vs 13.5%, all P<0.01). The severe and extremely severe pulmonary ventilation dysfunction was higher in complex type group than that in simple group(20.2% vs 8.6%, 21.4% vs 3.8%, all P<0.05). CONCLUSION: The types of pulmonary ventilation dysfunction in patients with pneumoconiosis are mainly obstructive and mixed. The pulmonary ventilation dysfunction tends to develop from obstructive to mixed with the increasing severity of pneumoconiosis. The pulmonary ventilation dysfunction in patients with complex type pneumoconiosis is more serious than that in patients with simple type pneumoconiosis. The HRCT image classification is related to the status of patients' pulmonary ventilation dysfunction.