Search

Sirt1 is a human homologue of the silent information regulator factor 2 (Sir2) and has an [NAD.sup.+]-dependent histone deacetylase activity. This protein is reported to have a pathogenetic role in muscle differentiation, diabetic nephropathy, and heart failure. In this study, we investigated the expression of sirt1 in spontaneously hypertensive rat (SHR) to obtain insight into the function of sirt1 in hypertensive cardiovascular hypertrophy. The gene and protein expression of sirt1 was increased in the heart in SHR compared with normotensive WKY rats. Sirt1 mRNA was not different in the aorta between SHR and WKY rats. Sirt1 mRNA expression in heart and aorta was not related to hemodynamic parameters in SHR. Hypertensive left ventricular hypertrophy was significantly and positively related to the expression of heart tissue sirt1 mRNA in SHR. Aortic hypertrophy, however, was not related to sirt1 mRNA in the aorta. The increased sirt1 protein expression was accompanied by severe cardiac hypertrophy in older SHR. These results suggest that the increase of sirt1 gene and protein expression in the heart was associated with cardiac hypertrophy. Key words: hypertension, sirt1, left ventricular hypertrophy, spontaneously hypertensive rat. Sir 1 est un homologue humain du regulateur de l'information silencieuse 2 (Sir2) et a une activite histone desacetylase dependante du NAD+. Il semble que cette proteine ait un role pathogene dans la differenciation cellulaire, la nephropathie diabetique et l'insuffisance cardiaque. Dans la presente etude, nous avons examine l'expression de sirtl chez des RSH pour avoir un apercu de la fonction de sirtl dans l'hypertrophie cardiovasculaire hypertensive. L'expression genique et proteique de sirtl a augmente dans le coeur des rats RSH par rapport a celle observee dans le coeur des WKY. L'ARNm de sirtl dans l'aorte n'a pas differe entre les deux souches de rats. L'expression de l'ARNm de sirtl dans le coeur et l'aorte n'a pas ete reliee au parametre hemodynamique chez les RSH. L'hypertrophie ventriculaire gauche hypertensive a ete correlee positivement avec l'expression de l'ARNm de sirtl dans le tissu cardiaque des RSH. Toutefois, l'hypertrophie aortique n'a pas ete associee a l'ARNm de sirtl dans l'aorte. L'augmentation de l'expression proteique de sirtl a ete accompagnee d'une hypertrophie cardiaque severe chez les RSH plus ages. Ces resultats donnent a penser que l'augmentation de l'expression genique et proteique de sirtl dans le coeur est liee a l'hypertrophie cardiaque. Mots-cles : hypertension, sirtl, hypertrophie cardiaque, rat spontanement hypertendu. [Traduit par la Redaction], Introduction Hypertension is a major risk factor for cardiovascular mortality and morbidity through its effects on target organs like the brain, heart, and kidney (Karpha and Lip 2006). End-organ damage [...]

Background and Aims: Microvascular invasion (MVI) is a key pathological factor that severely affects the postoperative prognosis of patients with hepatocellular carcinoma (HCC). However, no MVI classification schemes based on standardized gross sampling protocols of HCC are available at present., Methods: 119 HCC specimens were sampled at multiple sites (3-, 7-, and 13 points) for the optimum MVI detection rate. 16,144 resected HCCs were graded as M0, M1 or M2 by adopting three-tiered MVI grading (MVI-TTG) scheme based on the seven-point sampling protocol (SPSP). Survival analyses were performed on 2573 patients to explore the advantages of MVI-TTG., Results: The MVI detection rate determined by SPSP was significantly higher than that determined by the 3-point sampling method (34.5% vs. 47.1%, p = 0.048), but was similar to that determined by the 13-point sampling method (47.1% vs. 51.3%, p = 0.517). Among 16,144 resected HCCs, the proportions of M0, M1 and M2 specimens according to SPSP were 53.4%, 26.2% and 20.4%, respectively. Postoperative survival analysis in 2573 HCC patients showed that the 3-year recurrence rates in M0, M1 and M2 MVI groups were 62.5%, 71.6% and 86.1%, respectively (p < 0.001), and the corresponding 3-year overall survival (OS) rates were 94.1%, 87.5% and 67.0%, respectively (p < 0.001). M1 grade was associated with early recurrence, while M2 grade was associated with both early and late recurrence. MVI-TTG had a larger area under the curve and net benefit rate than the two-tiered MVI grading scheme for predicting time to recurrence and OS., Conclusions: SPSP is a practical method to balance the efficacy of sampling numbers and MVI detection rates. MVI-TTG based on SPSP is a better prognostic predictor than the two-tiered MVI scheme. The combined use of SPSP and MVI-TTG is recommended for the routine pathological diagnosis of HCC.

Lonicerae Japonicae Flos and Artemisiae Annuae Herba(LA or Jinqing) alcohol precipitation has various process parameters and complex process mechanism, and is one of the key units for manufacturing Reduning Injection. In order to identify the critical process parameters(CPPs) affecting the weight of the extract produced from the alcohol precipitation process, 259 batches of historical production data from 2017 to 2018 were collected, with a total of 829 318 data points. These data showed characteristics of large data, such as a large data volume, a low value density, and diverse sources. The data cleaning and feature extraction were first performed, and 48 feature variables were selected. The original data points were reduced to 9 936. Then, a combination of Pearson correlation analysis and grey correlation analysis were used to screen out 15 potential critical process parameters(pCPPs). After that, the partial least squares(PLS) was used in prediction of the weight of the extract, proving that the performance of predictive model based on 15 pCMAs is equivalent to that of predictive model based on 48 feature variables. The variable importance in projection(VIP) index was used to identify 9 CPPs, including 2 alcohol precipitation supernatant volume parameters, 4 initial extract weight parameters and 3 added alcohol volume parameters. As a result, the number of data points was 1 863, accounting for 0.28% of the original data. The big data analysis approach from a holistic point of view can effectively increase the value density of the original data. The critical process parameters obtained can help to accurately describe the quality transfer mechanism of the Jinqing alcohol precipitation process.

In this paper, a real time release testing(RTRT) model for predicting the disintegration time of Tianshu tablets was established on the basis of the concept of quality by design(QbD), in order to improve the quality controllability of the production process. First, 49 batches of raw materials and intermediates were collected. Afterwards, the physical quality attributes of all materials were comprehensively characterized. The partial least square(PLS) regression model was established with the 72 physical quality attributes of raw materials and intermediates as input and the disintegration time(DT) of uncoated tablets as output. Then, the variable screening was carried out based on the variable importance in the projection(VIP) indexes. Moisture content of raw materials(%HR), tapped density of wet masses(D&#95;c), hygroscopicity of dry granules(%H), moisture content of milling granules(%HR) and Carr's index of mixed granules(IC) were determined as the potential critical material attributes(pCMAs). According to the effects of interactions of pCMAs on the performance of the prediction model, it was finally determined that the wet masses' D&#95;c and the dry granules'%H were critical material attributes(CMAs). A RTRT model of the disintegration time prediction was established as DT=34.09+2×D&#95;c+3.59×%H-5.29×%H×D&#95;c,with R~2 equaling to 0.901 7 and the adjusted R~2 equaling to 0.893 3. The average relative prediction error of validation set for the RTRT model was 3.69%. The control limits of the CMAs were determined as 0.55 g·cm~(-3)&lt;D&#95;c&lt;0.63 g·cm~(-3) and 4.77&lt;%H&lt;7.59 according to the design space. The RTRT model of the disintegration time reflects the understanding of the process system, and lays a foundation for the implementation of intelligent control strategy of the key process of Tianshu Tablets.

To control the risks of powder caking and capsule shell embrittlement of Guizhi Fuling Capsules, a predictive model for hygroscopicity of contents in Guizhi Fuling Capsules was built. A total of 90 batches of samples, including raw materials, intermediate powders and capsules, were collected during the manufacturing of Guizhi Fuling Capsules. According to the production sequence, 47 batches were used as the calibration set, and the properties of raw materials and the four intermediate powders were comprehensively characterized by the physical fingerprint. Then, the partial least squares(PLS) model was developed with the content hygroscopicity as the response variable. The variable importance in projection(VIP), variance inflation factor(VIF) and regression coefficients were used to screen out potential critical material attributes(pCMAs). As a result, five pCMAs from 54 physical parameters were screened out. Furthermore, different models were built by different combinations of pCMAs, and their predictive robustness of 43 batches was evaluated on the basis of the validation set. Finally, the tap density(D&#95;c) of wet granules obtained from wet granulation and the angle of repose(α) of raw materials were identified as the critical material attributes(CMAs) affecting the hygroscopicity of the contents of Guizhi Fuling Capsules. The prediction model established with the two CMAs as independent variables had an average relative prediction error of 2.68% for samples in the validation set, indicating a good accuracy of prediction. This paper proved the feasibility of predictive modeling toward the control of critical quality attributes of Chinese medicine oral solid dosage(OSD). The combination of the continuous quality improvement, the industrial big data and the process modeling technique paved the way for the intelligent manufacturing of Chinese medicine oral solid preparations.

Objective: To discuss the relationship between infestation of Demodex folliculorum and facial epidermal neoplasm., Methods: A retrospective analysis was made with the pathological data of 153 cases collected in the recent four years on facial basal cell carcinoma, squamous cell carcinoma, seborrheic keratosis and trichilemmoma. The infection rate of Demodex folliculorum in the four types of neoplasm was evaluated and the relationship between the infection rate and the location of neoplasm and age was analyzed by V2 test., Results: There was a significant difference in the infestation rate of Demodex folliculorum in the four types of epidermal neoplasm(P < 0.05), with the highest rate in basal cell carcinoma(56%), compared with seborrheic keratosis (21%), trichilemmoma (20%), and squamous cell carcinoma (14%). The infestation rate of Demodex folliculorum was significantly different in variant locations of epidermal neoplasm (P < 0.05). The highest infestation rate was in cases of nasal neoplasm (71%), compared with other parts. In addition, among twelve cases of Demodex folliculorum positive nasal neoplasm, nine were basal cell carcinoma; ten of thirty-six basal cell carcinoma occurred on nose., Conclusion: The highest infestation rate of Demodex folliculorum was in cases of nasal epidermal neoplasm compared with other locations, and the cases of basal cell carcinoma showed the highest infestation rate among the four types of neoplasm.