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.

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

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:Papillary renal cell carcinomas (PRCC) is relatively infrequent, and there are few related researches in China. This study aimed to summarize the clinical and pathological features of PRCC, and evaluate prognostic factors for patients treated with surgery.Methods:A total of 64 patients who under-went surgery for PRCC were retrospectively assessed. PRCC tissue slides from each patient were reviewed for type (ⅠorⅡ), grade, TNM stage, coagulative tumor necrosis and microvascular invasion. We estimated overall survival using the Kaplan-Meier method. Multivariate analysis was done according to the Cox proportional hazards model of factors statistically signiifcant on univariate analysis. Results:The incidence rate of ENE was 6.04%in RCC, the median age was 55 (range 22 to 78) years. The comparison of the 22 (534.4%) typeⅠPRCCs and 42 (65.6%) typeⅡPRCCs revealed that typeⅡtumors were associated with a greater stage and grade more often. The median follow-up was 46 months (range 19 to 133). Of the 64 patients, 14 died, (4.5%) with typeⅠand 13 (31.0%) with typeⅡtumors (P=0.018). The overall survival rate was 85.7%in typeⅠtumors and 55.8%in typeⅡtumors, respectively. Univariate analysis identiifed symptoms at presentation, tumor type, TNM stage and grade as prognostic factors. On multivariate analysis only metastatic RCC remained associated with decreased overall survival (HR:14.78, P=0.004). Conclusion:The per-centage of PRCC is lower and typeⅡPRCC is relatively common compared with foreign data. Metastasis at diagnosis is an independent predictive parameter of overall survival in Chinese patients with PRCC.

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.

Purpose To investigate the clinicopathological features of multilocular cystic renal cell carcinoma ( MCRCC) , and to im-prove the understanding of this disease. Methods Thirty-two of MCRCC were studied by clinic data, pathological features and immu-nophenotype. All the thirty-two cases were followed up. Results In this study, thirty-two patients were diagnosed as MCRCC with a male-to-female ratio of 2.2 : 1, thirteen of whom had the tumor in the left kidney, eighteen in the right kidney, another in the double kidneys. The mean of tumor diameter was 4.6 cm (1.0~8.0 cm). Eleven patients underwent radical nephrectomy while the other 21 patients received nephron sparing surgery. Microscopically, all the cases were multiocular, lined in the cyst wall by a single layer of tumor cells with the clear or pale cytoplasm and Fuhrman grade 1 nuclei. Occasionally, the lining consisted of several layers of tumor cells or a few small papillae were present. The linings of the cyst wall were rich in thin-wall blood vessels. Immunohistochemically, the tumor cells were positive for CK(32/32), CK7(25/32), EMA(32/32), CD10(23/32) and vimentin(20/32), while negative for CD68. Conclusions MCRCC is characteristic by low grade nuclei, lacking solid nodules, and in the cyst wall, and has a favourable prognosis. The rich in thin-wall blood vessels and the lining cells with the clear or pale cytoplasm are diagnosis clues.

Objective To determine the relationship between brachial-ankle pulse wave velocity(baPWV)and Rho associated coiled coil protein kinase(ROCK)activity with the cardiovascular disease(CVD).Methods 168 patients with CVD were divided in-to the CVD group(123 cases)and the non-CVD group(45 cases)based on the results of coronary angiography.The baPWV value and the ROCK activity were detected.The CVD group were subdivided into the single vessel,double vessels and multiple vessels le-sions groups.Results The baPWV value and ROCK activity in the CVD group were significantly higher than those in the non-CVD group(P<0.05).The more the lesion vessels,the higher the baPWV value(P<0.05).Conclusion The baPWV and ROCK activi-ty are associated with CVD.Therefore,the combined measurement of baPWV and ROCK levels could be used to assess CVD and its risk degree.

Objective To investigate the correlation of arterial compliance and carotid atherosclerosis in patients with type-2 diabetes.Methods Eighty cases of type-2 diabetic patients and 80 control subjects were recruited into the study.Brachial-ankle pulse wave velocity(BaPWV)and ankle-brachial index(ABI)were measured with atherosclerosis diagnostic devices VP-1000.The inner-membrane and medium-membrane thickness(IMT)of the common carotid artery and plaque were detected with color Doppler ultrasound.The difference of the pulse wave velocity in the subjects with carotid plaques were compared between the two groups.The correlations of carotid IMT with BaPWV and ABI were also analyzed.Results In the diabetic patients group,BaPWV([1752 ± 213]cm/s)was higher than that of normal control group([1279 ± 159]cm/s)(P ＜ 0.01);ABI in diabetic patients group(0.95 ± 0.13)was lower than that of control group(1.28 ± 0.17),(P ＜ 0.01).In the diabetic patients group,the incidences of carotid IMT thickening(45.0％)and plaques(35.0％)were both higher than that of control group(27.5％ and 10.8％,respectively)(P ＜ 0.05).In the diabetic patients group,the cases with carotid plaques had a higher BaPWV([1810 ± 296]cm/s)than those without([1480 ± 304]cm/s)(P ＜ 0.01).BaPWV was positively correlated with carotid IMT(r =0.271,P ＜ 0.05).ABI and IMT was negatively correlated(r =-0.406,P ＜ 0.05).Conclusion BaPWV and carotid IMT was positively correlated,while ABI and IMT was negatively correlated.BaPWV and ABI are indicators which are practicable and effective to evaluate the stiffness of peripheral arteries in patients with diabetes.