Purpose To investigate the clinicopathological features and prognosis of adult large B-cell lymphoma with IRF4 rearrangement(LBCL-IRF4r).Methods Clinical data of 63 adult LBCL-IRF4r cases were collected.The EnVision two-step method was employed for immunohistochemical staining,and fluorescence in situ hybridization was used to detect rearrangements or deletions of the IRF4,BCL2,MYC,BCL6,and TP53 genes.The relationship be-tween clinicopathological features and prognosis was analyzed and compared with data from 132 adult non-specified dif-fuse large B-cell lymphoma(DLBCL)cases.Results Among the 63 adult LBCL-IRF4r patients,the male to female ratio was 1.1∶1,with a median age of 54.0 years(range 20-84 years),and 14 cases(22.2％)were＜40 years old,24 cases(38.1％)were between 40 and 60 years old,and 25 cases(39.7％)were＞60 years old.18 cases(28.6％)were involved in Waldeyer's ring,along with 8 cases(12.7％)in cervical lymph nodes,7 cases(11.1％)in other lymph nodes and lymphatic organs,13 cases(20.6％)in stomach,4 cases(6.4％)in intestine,and 13 cases(20.6％)in other extranodal sites.63 cases showed IRF4 rearrangements,with no BCL2 and MYC translocations(0/58),30.9％(17/55)had BCL6 translocations,and 16.3％(8/49)had TP53 deletions.59 pa-tients were followed up for a median of 28 months(range 1-65 months).48 patients(81.4％)achieved complete re-sponse,10 patients(16.9％)experienced disease progression or relapse,and 3 patients(5.1％)died.Univariate a-nalysis showed that lactate dehydrogenase level,Ann Arbor stage,international prognostic index(IPI)score,growth pattern,Hans classification,and double expression of BCL2 and C-MYC were significantly associated with progression-free survival.Age,Ann Arbor stage,and IPI score were significantly associated with overall survival.Multivariate Cox regression analysis showed that double expression of BCL2 and C-MYC was an independent prognostic factor for pro-gression-free survival.Adult LBCL-IRF4r had significantly higher complete response rate and progression-free survival than adult DLBCL.Conclusion LBCL-IRF4r occurs in adults of all age groups,commonly affecting Waldeyer's ring,cervical lymph nodes,and gastrointestinal tract,and has a favorable clinical prognosis.

Purpose To investigate the clinical,imaging,and pathological features of Kikuchi-Fujimoto disease(KFD).Methods A retrospective analysis was conducted on 123 pathologically confirmed KFD cases.Clinical and imaging data were collected,and histopathological features were evaluated using HE staining,immunohistochemistry,in situ hybridization for EBER,and molecular analyses(TCR/Ig gene rearrangements by PCR with capillary electro-phoresis).Results Among the 123 patients,the male-to-female ratio was 1∶2,with a median age of 30 years.All patients presented with lymphadenopathy.Among 30 hospitalized patients,63.3％(19/30)had fever,and 23.3％(7/30)had concurrent autoimmune diseases.Of the 12 patients who underwent PET-CT,91.7％(11/12)were sus-pected of malignancy,prompting biopsy recommendations.Among 47 consultation cases,27.7％(13/47)were ini-tially misdiagnosed as lymphoma.Histopathological examination revealed proliferative,necrotic,and xanthomatous phases,which coexisted or occurred independently.The proliferative phase was characterized by atypical lymphocytes and histiocytes,the necrotic phase by abundant eosinophilic fibrin deposits and nuclear debris,and the xanthomatous phase by clusters of foam-like histiocytes.Immunohistochemically analyses revealed that atypical lymphocytes were neg-ative for CD20,CD4,and CD56 but positive for CD3,CD8,TIA1,Granzyme B,and Perforin.Histiocytes expressed CD68,CD163,and MPO,while CD123-positive plasmacytoid dendritic cells were predominantly located around the le-sions and blood vessels.EBER was positive in individual cells in 4 cases.TCR gene rearrangement was positive in 2 cases and suspected positive in 3 cases,while Ig rearrangement was positive and suspected positive in 1 case each.Conclusion KFD exhibits clinical,imaging,and pathological features that can mimic lymphoma,highlighting the im-portance of accurate diagnosis to avoid misdiagnosis and inappropriate treatment.

Purpose To investigate the clinicopathological features and prognosis of adult large B-cell lymphoma with IRF4 rearrangement(LBCL-IRF4r).Methods Clinical data of 63 adult LBCL-IRF4r cases were collected.The EnVision two-step method was employed for immunohistochemical staining,and fluorescence in situ hybridization was used to detect rearrangements or deletions of the IRF4,BCL2,MYC,BCL6,and TP53 genes.The relationship be-tween clinicopathological features and prognosis was analyzed and compared with data from 132 adult non-specified dif-fuse large B-cell lymphoma(DLBCL)cases.Results Among the 63 adult LBCL-IRF4r patients,the male to female ratio was 1.1∶1,with a median age of 54.0 years(range 20-84 years),and 14 cases(22.2％)were＜40 years old,24 cases(38.1％)were between 40 and 60 years old,and 25 cases(39.7％)were＞60 years old.18 cases(28.6％)were involved in Waldeyer's ring,along with 8 cases(12.7％)in cervical lymph nodes,7 cases(11.1％)in other lymph nodes and lymphatic organs,13 cases(20.6％)in stomach,4 cases(6.4％)in intestine,and 13 cases(20.6％)in other extranodal sites.63 cases showed IRF4 rearrangements,with no BCL2 and MYC translocations(0/58),30.9％(17/55)had BCL6 translocations,and 16.3％(8/49)had TP53 deletions.59 pa-tients were followed up for a median of 28 months(range 1-65 months).48 patients(81.4％)achieved complete re-sponse,10 patients(16.9％)experienced disease progression or relapse,and 3 patients(5.1％)died.Univariate a-nalysis showed that lactate dehydrogenase level,Ann Arbor stage,international prognostic index(IPI)score,growth pattern,Hans classification,and double expression of BCL2 and C-MYC were significantly associated with progression-free survival.Age,Ann Arbor stage,and IPI score were significantly associated with overall survival.Multivariate Cox regression analysis showed that double expression of BCL2 and C-MYC was an independent prognostic factor for pro-gression-free survival.Adult LBCL-IRF4r had significantly higher complete response rate and progression-free survival than adult DLBCL.Conclusion LBCL-IRF4r occurs in adults of all age groups,commonly affecting Waldeyer's ring,cervical lymph nodes,and gastrointestinal tract,and has a favorable clinical prognosis.

Purpose To investigate the clinical,imaging,and pathological features of Kikuchi-Fujimoto disease(KFD).Methods A retrospective analysis was conducted on 123 pathologically confirmed KFD cases.Clinical and imaging data were collected,and histopathological features were evaluated using HE staining,immunohistochemistry,in situ hybridization for EBER,and molecular analyses(TCR/Ig gene rearrangements by PCR with capillary electro-phoresis).Results Among the 123 patients,the male-to-female ratio was 1∶2,with a median age of 30 years.All patients presented with lymphadenopathy.Among 30 hospitalized patients,63.3％(19/30)had fever,and 23.3％(7/30)had concurrent autoimmune diseases.Of the 12 patients who underwent PET-CT,91.7％(11/12)were sus-pected of malignancy,prompting biopsy recommendations.Among 47 consultation cases,27.7％(13/47)were ini-tially misdiagnosed as lymphoma.Histopathological examination revealed proliferative,necrotic,and xanthomatous phases,which coexisted or occurred independently.The proliferative phase was characterized by atypical lymphocytes and histiocytes,the necrotic phase by abundant eosinophilic fibrin deposits and nuclear debris,and the xanthomatous phase by clusters of foam-like histiocytes.Immunohistochemically analyses revealed that atypical lymphocytes were neg-ative for CD20,CD4,and CD56 but positive for CD3,CD8,TIA1,Granzyme B,and Perforin.Histiocytes expressed CD68,CD163,and MPO,while CD123-positive plasmacytoid dendritic cells were predominantly located around the le-sions and blood vessels.EBER was positive in individual cells in 4 cases.TCR gene rearrangement was positive in 2 cases and suspected positive in 3 cases,while Ig rearrangement was positive and suspected positive in 1 case each.Conclusion KFD exhibits clinical,imaging,and pathological features that can mimic lymphoma,highlighting the im-portance of accurate diagnosis to avoid misdiagnosis and inappropriate treatment.

From the perspective of technical evaluation, this study reviewed the current situation of application and clinical application of medical device products were detected by liquid chromatography-tandem mass spectrometry in the market in recent years. The regulatory requirements of these products in China, USA, EU and Japan were compared and analyzed, and the monitoring situation of adverse events after listing, the standards for reference and the domestic and foreign regulatory documents were combined, the clinical application and regulatory risks of the product were analyzed. The problems such as pre-treatment, system matching, adequacy of performance index requirements, inter-room consistency, reference interval and registration unit were discussed and suggestions for supervision were given, with a view to the field of product R&D and production, review and approval of supervision to provide technical reference.
Chromatography, Liquid/methods* ; Tandem Mass Spectrometry/methods* ; Reference Standards ; Japan

Smart manufacturing still remains critical challenges for pharmaceutical manufacturing. Here, an original data-driven engineering framework was proposed to tackle the challenges. Firstly, from sporadic indicators to five kinds of systematic quality characteristics, nearly 2,000,000 real-world data points were successively characterized from Ginkgo Folium tablet manufacturing. Then, from simplex to the multivariate system, the digital process capability diagnosis strategy was proposed by multivariate C_pk integrated Bootstrap-t. The C_pk of Ginkgo Folium extracts, granules, and tablets were discovered, which was 0.59, 0.42, and 0.78, respectively, indicating a relatively weak process capability, especially in granulating. Furthermore, the quality traceability was discovered from unit to end-to-end analysis, which decreased from 2.17 to 1.73. This further proved that attention should be paid to granulating to improve the quality characteristic. In conclusion, this paper provided a data-driven engineering strategy empowering industrial innovation to face the challenge of smart pharmaceutical manufacturing.

0bjective To investigate the clinicopathological features,immunohistochemical phenotypes, molecular genetic alterations,diagnosis and differential diagnosis of inflammatory myofibroblastic tumor (IMT) of the urinary bladder. Methods:Ten cases of IMT of the urinary bladder (three cases at Ningbo Diagnostic Pathology Center from September 2011 to December 2020, five in-house diagnosed cases and two consultation cases at Shanghai Rui Jin Hospital from June 2011 to December 2020) were collected retrospectively. The clinicopathologic features and immunophenotypic profiles were studied by light microscopy and immunohistochemistry (EnVision method). The translocation of ALK gene was detected by fluorescence in situ hybridization (FISH).Results:Of the 10 patients, eight were male and two were female. The patients′ age range was 16 to 62 years (median 36 years).The main clinical presentation was hematuria and urinary irritation. Three cases were located at the dome of the urinary bladder, four cases were in the left lateral wall and the remaining three cases were in the right lateral wall. The tumor size ranged from 1.5 cm to 8.5 cm. In eight cases, the tumors were mainly submucosal, and in some cases extending to the muscular layer of the urinary bladder. In two cases, the tumors were mainly located in the muscular layer and focally extended to the submucosa and adventitia. Histologically, four cases had the nodular fasciitis-like pattern, three cases had fibrohistiocytoma-like pattern, two cases had mixed histologic patterns and the remaining case showed leiomyosarcoma-like histologic features. Immunohistochemically, the tumor cells expressed SMA (10/10),calponin (9/10),desmin (6/10) and CKpan (9/10). Cytoplasmic staining for ALK1 and ALK (5A4) was detected in 7 of 10 cases and 8 of 10 cases, respectively. Nuclear and cytoplasmic staining for ALK (D5F3) was detected in 7 of 10 cases. Among eight cases with material available for FISH analysis, ALK rearrangement was present in five cases. Follow-up data were available in eight patients and none had local recurrence nor distant metastasis.Conclusion:IMT of the urinary bladder is an uncommon mesenchymal neoplasm with intermediate malignant potential.It has special clinicopathologic features, and a minority of cases have local tumor recurrence.

Objective:To analyze the differences in ankle brachial index(ABI), central arterial pressure(CAP)and branchial-ankle pulse wave velocity(baPWV)in elderly patients with different degrees of coronary heart disease(CHD), and to provide a basis for the assessment of CHD.Methods:From January 2018 to July 2019, 52 elderly patients with CHD treated in our hospital were selected as the observation group, and divided into Observation Group A(mild, single-vessel disease), Observation Group B(double-vessel lesions)and Observation Group C(multivessel lesions or trunk lesions). Besides, 32 healthy people(the degree of coronary artery stenosis < 50%)were selected as the control group.ABI, CAP and baPWV were measured and compared.Results:Patients in the observation groups were associated with significantly lower ABI [(1.01±0.14) vs.(1.12±0.15), t=-3.403, P=0.001]and higher CAP [(63.9 ± 11.8)mmHg vs.(56.3 ± 10.5)mmHg, t=2.987, P=0.002]and baPWV [(1675.9±259.5)cm/s vs.(1517.2±283.4)cm/s, t=2.628, P=0.005]than those in the control group.For patients in Observation Groups A, B, C and the control group, the ABI values were (1.07±0.13, 0.95±0.14, 0.92±0.17 and 1.12±0.15, F=12.118, P=0.085), the baPWV values were (1685.2±276.8) cm/s, (1680.8±255.4) cm/s, (1667.4±232.6) cm/s and (1517.2±283.4) cm/s( F=0.573, P=0.573), and the CAP values were (62.7±12.3) mmHg, (64.2±11.5) mmHg, (69.1±10.6) mmHg and (56.3±11.8) mmHg, respectively( F=1.212, P=0.053). ABI levels in Observations Groups B and C were higher than those in the control group( t=3.938, P=0.000; t=-5.534, P=0.000). Additionally, levels of baPWV in Observation Group A was higher than in the control group( t=2.628, P=0.005), and CAP levels in Observation Groups A( t=2.349, P=0.011), B( t=2.293, P=0.013), C( t=3.697, P=0.000)were significantly higher than in the control group, though there was no significant difference between the observation groups( F=1.212, P=0.053). Conclusions:CAP and baPWV have the potential to be used as diagnostic parameters for elderly CHD patients, but their specificity for detecting the degree of coronary stenosis is poor.ABI is significantly different between patients with different degrees of CHD and can be used as a basis for evaluation of disease severity.

OBJECTIVETo analyze the risk factors to impact biochemical recurrence after radical prostatectomy.

METHODSA total of 1 090 patients who received radical prostatectomy from May 2002 to December 2013 in Department of Urology of Fudan University Shanghai Cancer Center were recruited. The average age of the patients was 67.9 years (ranged from 41 to 84 years) and the average preoperative prostate specific antigen (PSA) level was 32.7 (ranged from 3.2 to 256.3) µg/L. The distribution of patients with respect to clinical stage was: 20.09% (219/1 090) had T1, 50.09% (546/1 090) had T2 and 29.82% (325/1 090) had T3. The biochemical-free-survival curve was drawn by Kaplan-Meier method and the univariate and multivariate Cox regression models were used to evaluate the clinical and pathological variables for the development of biochemical recurrence.

RESULTSOf all the 1 090 patients, the biochemical recurrence free survival was 95.99%, 81.90% and 70.89% at 1, 3 and 5 years. PSA level at diagnosis (P=0.000), neo-adjuvant hormonal therapy (P=0.001), pre-operative Gleason score (P=0.000), clinical stage (P=0.010), surgical margin status (P=0.028), post-operative Gleason score (P=0.000), pathological stages (P=0.000) and pelvic lymph-node metastasis (P=0.000) were associated with biochemical recurrence in the univariate analysis. However, in the multivariate analysis, only PSA level at diagnosis (P=0.000), pre-operative Gleason score (P=0.020), pathological stages (P=0.014) and pelvic lymph-node metastasis (P=0.017) were independent prognostic factors.

CONCLUSIONFor the patients who received radical prostatectomy, PSA level at diagnosis, pre-operative Gleason score, pathological stages and pelvic lymph-node metastasis status are independent prognostic factors for biochemical recurrence.

Adult ; Aged ; Aged, 80 and over ; China ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Pelvis ; pathology ; Postoperative Period ; Proportional Hazards Models ; Prostate-Specific Antigen ; blood ; Prostatectomy ; Prostatic Neoplasms ; pathology ; surgery ; Risk Factors

Background and purpose:To perform whole mount technique in the diagnosis of the prostate cancer could provide orientation to the specimen. Whole mount technique has great value in pathologic diagnosis and morphological research. However, limited by the specimen-making technique, shortage of equipment and heavy workload, this technique has not been generally accepted in China. The aim of this study was to evaluate the signiifcance of whole mount technique in the diagnosis of the prostate cancer by comparing the clinical and pathological variables between whole mount patients and conventional ones after radical prostatectomy (RP).Methods:A total number of 229 patients’ whole mount RP specimens were recruited in the study from Dec. 2012 to Feb. 2014. The control group included 393 patients’ specimens which underwent conventional sampling from Jan. 2010 to Jun. 2012. We compared the clinical and pathological variables between the groups, including age, preoperative PSA level, methods of diagnosis, preliminary diagnostic Gleason score, clinical T stage, postoperative Gleason score, pathological T stage, positive surgical margin, extraprostatic extension, seminal vesicle invasion and pelvic lymph node metastasis.Results:Two groups shared similar preoperative parameters. Also there was no signiifcant difference between the whole mount and the conventional sampling groups in postoperative Gleason score, pathological T stage, extraprostatic extension and pelvic lymph node metastasis. However, positive surgical margin and seminal vesicle invasion rates were much higher in the whole mount group than the control one and both of the differences reached statistical signiifcance (26.2%vs 17.6%, 23.1%vs 17.0%;P=0.010, 0.025)Conclusion:After compared the clinical and pathological variables, we could conclude that whole mount technique has prevalence in the diagnosis of the positive surgical margin and seminal vesicle invasion compared with the conventional sampling technique. Thus, whole mount technique should be strongly recommended in the diagnosis of prostate cancer.