[Application progress on data-driven technologies in intelligent manufacturing of traditional Chinese medicine extraction].

The application of new-generation information technologies such as big data, the internet of things(IoT), and cloud computing in the traditional Chinese medicine(TCM)manufacturing industry is gradually deepening, driving the intelligent transformation and upgrading of the TCM industry. At the current stage, there are challenges in understanding the extraction process and its mechanisms in TCM. Online detection technology faces difficulties in making breakthroughs, and data throughout the entire production process is scattered, lacking valuable mining and utilization, which significantly hinders the intelligent upgrading of the TCM industry. Applying data-driven technologies in the process of TCM extraction can enhance the understanding of the extraction process, achieve precise control, and effectively improve the quality of TCM products. This article analyzed the technological bottlenecks in the production process of TCM extraction, summarized commonly used data-driven algorithms in the research and production control of extraction processes, and reviewed the progress in the application of data-driven technologies in the following five aspects: mechanism analysis of the extraction process, process development and optimization, online detection, process control, and production management. This article is expected to provide references for optimizing the extraction process and intelligent production of TCM.

Traumatic injury mortality prediction (TRIMP-ICDX): A new comprehensive evaluation model according to the ICD-10-CM codes.

Various assessment methods based on the International Classification of Diseases, Tenth Edition, Clinical Modification (ICD-10-CM), such as ICD-10-CM Injury Severity Score (ICISS), trauma mortality prediction model (TMPM-ICD10), and injury mortality prediction (IMP-ICDX), are purely anatomic trauma assessment, which need to be further improved. Traumatic injury mortality prediction (TRIMP-ICDX) is a comprehensive assessment method based on anatomic injuries and incorporating available information to determine whether it is superior to Trauma and Injury Severity Score (TRISS) and IMP-ICDX in predicting trauma outcomes. This retrospective cohort study was based on data from 704,287 trauma patients admitted to 710 trauma centers in the National Trauma Data Bank of the United States in 2016. The TRIMP-ICDX was established using anatomical injury, physiological reserves, and physiological response indicators. Its performance was compared with the IMP-ICDX and TRISS by examining the area under the receiver operating characteristic curve (AUC), calibration (Hosmer-Lemeshow goodness-of-fit test, HL), and the Akaike information criterion (AIC). The TRIMP-ICDX showed significantly better discrimination (AUCTRIMP-ICDX 0.968; 95% confidence interval (CI), 0.966-0.970, AUCTRISS 0.922; 95% CI, 0.918-0.925, and AUCIMP-ICDX 0.894; 95% CI, 0.890-0.899), better calibration (HLTRIMP-ICDX 5.6; 95% CI, 3.0-8.0, HLTRISS 72.7; 95% CI, 38.4-104.5, and HLIMP-ICDX 53.1; 95% CI, 26.6-77.8), and a lower AIC (AICTRIMP-ICDX 24,774, AICTRISS 30,753, and AICIMP-ICDX 32,780) compared with TRISS and IMP-ICDX. Similar results were found in statistical comparisons among different body regions. As a comprehensive evaluation method based on the ICD-10-CM lexicon TRIMP-ICDX is significantly better than IMP-ICDX and TRISS with respect to both discriminative power and calibration. The TRIMP-ICDX should become a research method for the comprehensive evaluation of trauma severity.

A traumatic injury mortality prediction (TRIMP) based on a comprehensive assessment of abbreviated injury scale 2005 predot codes.

Abbreviated Injury Scale (AIS)-based systems such as injury severity score (ISS), exponential injury severity score (EISS), trauma mortality prediction model (TMPM), and injury mortality prediction (IMP), classify anatomical injuries with limited accuracy. The widely accepted alternative, trauma and injury severity score (TRISS), improves the prediction rate by combining an anatomical index of ISS, physiological index (the Revised Trauma Score, RTS), and the age of patients. The study introduced the traumatic injury mortality prediction (TRIMP) with the inclusion of extra clinical information and aimed to compare the ability against the TRISS as predictors of survival. The hypothesis was that TRIMP would outperform TRISS in prediction power by incorporating clinically available data. This was a retrospective cohort study where a total of 1,198,885 injured patients hospitalized between 2012 and 2014 were subset from the National Trauma Data Bank (NTDB) in the United States. A TRIMP model was computed that uses AIS 2005 (AIS_05), physiological reserve and physiological response indicators. The results were analysed by examining the area under the receiver operating characteristic curve (AUC), the Hosmer-Lemeshow (HL) statistic, and the Akaike information criterion. TRIMP gave both significantly better discrimination (AUCTRIMP, 0.964; 95% confidence interval (CI), 0.962 to 0.966 and AUCTRISS, 0.923; 95% CI, 0.919 to 0.926) and calibration (HLTRIMP, 14.0; 95% CI, 7.7 to 18.8 and HLTRISS, 411; 95% CI, 332 to 492) than TRISS. Similar results were found in statistical comparisons among different body regions. TRIMP was superior to TRISS in terms of accurate of mortality prediction, TRIMP is a new and feasible scoring method in trauma research and should replace the TRISS.

Gambogic Acid Shows Anti-Proliferative Effects on Non-Small Cell Lung Cancer (NSCLC) Cells by Activating Reactive Oxygen Species (ROS)-Induced Endoplasmic Reticulum (ER) Stress-Mediated Apoptosis.

BACKGROUND Gambogic acid (AG) is believed to be a potent anti-cancer agent. ER (endoplasmic reticulum) stress-induced cell apoptosis was identified as one of the anti-proliferative mechanisms of several anti-cancer agents. In this study, we investigated the involvement of ER stress-induced apoptosis in the anti-proliferative effect of GA on NSCLC (non-small cell lung cancer) cells. MATERIAL AND METHODS GA at 0, 0.5, and 1.0 µmol/l was used to treat A549 cells. We also used the ER stress-specific inhibitor 4-PBA (4-phenylbutyric acid) (1 µmol/l) to co-treat the cells incubated with GA. Cell viability was assessed by MTT (methyl thiazolyl tetrazolium) assay. Cell apoptosis was evaluated by MTT (methyl thiazolyl tetrazolium) assay. Intracellular ROS (reactive oxygen species) production was detected by DCFH-DA (2,7- dichloro-dihydrofluorescein diacetate) florescent staining. Western blotting was used to assess the expression and phosphorylation levels of protein. RESULTS GA treatment significantly reduced cell viabilities of NSCLC cells in a concentration-dependent manner. GA treatment increased intracellular ROS level, expression levels of GRP (glucose-regulated protein) 78, CHOP (C/EBP-homologous protein), ATF (activating transcription factor) 6 and caspase 12, as well as the phosphorylation levels of PERK (protein kinase R-like ER kinase) and IRE (inositol-requiring enzyme) 1alpha. Co-treatment of 4-PBA dramatically impaired the inhibitory effect of GA on cell viability. 4PBA co-treatment also decreased expression levels of GRP78, CHOP, ATF6, and caspase12, as well as the phosphorylation levels of PERK and IRE1alpha, in GA-treated NSCLC cells, without affecting ROS levels. CONCLUSIONS GA inhibited NSCLC cell proliferation by inducing ROS-induced ER stress-medicated apoptosis of NSCLC cells.

Gambogic Acid Induces Apoptosis of Non-Small Cell Lung Cancer (NSCLC) Cells by Suppressing Notch Signaling.

BACKGROUND Activation of Notch signaling was found to be associated with cancer. Gambogic acid (GA) was reported to be an anti-cancer agent. This study investigated the anti-cancer effect of GA on human non-small cell lung cancer (NSCLC) cells. Involvement of the Notch pathway was also studied. MATERIAL AND METHODS GA at 0, 0.5, 0.75, and 1.0 µmol/l was used to incubate A549 and SPC-A1 cells. MTT assay was used to determine the cell viability. TUNEL assay was used to detect the apoptosis. Western blotting was used to evaluate protein expression levels, protein phosphorylation levels, and nuclear translocation levels. RESULTS Notch signaling pathway was activated in NSCLC cells. GA treatment significantly inhibited NSCLC cell viability and increased cell apoptosis. GA treatment significantly decreased the expression levels of DLL1, DLL3, DLL4, Jagged1, Jagged2, Bcl2, and PK3K, inhibited NICD nuclear translocation and Akt phosphorylation, and increased expression level of active caspase3. CONCLUSIONS GA inhibited NSCLC cell viability by inducing apoptosis. Inhibition of the Notch signaling pathway was the mechanism involved in the anti-proliferation effect of GA on NSCLC.

[Effect of cisplatin on the expression of Pokemon gene: experiment with different human lung cancer cells].

OBJECTIVE: To investigate the correlation between Pokemon gene and cisplatin mechanism. METHODS: Human lung adenocarcinoma cells of the lines A549 and AGZY83-a, human lung squamous carcinoma cells of the line HE-99, and human giant cell lung cancer cells of the line 95D were cultured and cisplatin was added into the medium. Other lung cancer cells of the above mentioned lines were cultured in the medium without cisplatin and were used as control groups. RT-PCR and Western blotting were used to detect the mRNA and protein expression of Pokemon. RESULTS: Pokemon mRNA and protein were expressed highly in all the 4 cell lines. The Pokemon gene expression did not changed significantly after cisplatin treatment groups. There were not significant differences in the mRNA and protein expression of Pokemon among the 4 experiment groups and the control groups (all P > 0.05). CONCLUSION: Cisplatin has no effect on the Pokemon gene expression of the human lung cancer cells.

[Suppression of RASSF1A gene on human esophageal carcinoma cells: experiments in vitro and in vivo].

OBJECTIVE: To investigate the effect of Ras association domain family 1A (RASSF1A) gene, a new tumor suppressor gene (TSG), on tumorigenesis of human esophageal carcinoma cells. METHODS: pcDNA3.1 (+)-RASSF1A, a plasmid containing RASSF1A gene, and the blank plasmid pcDNA3.1 (+) were transfected into human esophageal carcinoma cells of the line EC9706. The expression of RASSF 1A protein was examined by Western blotting. The changes of cell cycle of stably-transfected cells were determined by flow cytometry (FCM), and the cellular proliferation was analyzed by MTT assay. Fifteen nude mice were randomly divided into 3 groups to be inoculated subcutaneously with EC9706 cells transfected with pcDNA3.1 (+)-RASSF1A, EC9706 cells transfected with pcDNA3.1 (+), and untransfected EC9706 cells respectively. Other 5 nude mice were used as controls. Four weeks later, the mice were killed to take out the carcinoma tissues. FCM was used to analyze the cell cycle. RESULTS: Western blotting showed that RASSF1A protein was expressed highly in the stably transfected cells. The cell viability and growing speed were decreased obviously in the cells expressing of RASSF1A (both P < 0.01); FCM showed that the proportion of cells at the G(1) phase of the EC9706 cells expressing RASSF1A was significantly higher than those in the blank plasmid group and untransfected group (both P < 0.01). The size of the EC9706 cells obtained from the nude mice inoculated with the EC9706 cells transfected with pcDNA3.1 (+)-RASSF1A was significantly smaller than those of the pcDNA3.1 (+) group and blank plasmid group (both P < 0.05). CONCLUSION: Expression of exogenous RASSF1A inhibits the progression of human esophageal carcinoma cells in vitro and in vivo. As a tumor suppressor gene, it plays an important role in origination, progression and metastasis of esophageal carcinoma.

[Hypermethylation of promoter region of RAS association domain family gene1A in esophageal squamous cell carcinoma and significance thereof].

OBJECTIVE: To investigate the hypermethylation of the promoter region of RAS association domain family gene1A (RASSF1A) and its relationship with esophageal squamous cell carcinoma. METHODS: Sixty-six patients with esophageal squamous carcinoma, 60 males and 6 females, aged 59 +/- 8 (44 - 76), underwent resection of the tumor. Methylation-specific PCR (MSP) was used to detect the hypermethylation of promoter region of RASSF1A in the carcinoma tissues and the adjacent normal tissues. RESULTS: The hypermethylation rate of RASSF1A promoter in the tumor tissues was 48. 5% (32/66), significantly higher than that in the adjacent normal tissues (6.1%, 4/66, P < 0.05). The hypermethylation rate of RASSF1A promoter of the patients with lymph node metastasis was 61.1%, significantly higher than that of the patients without lymph node metastasis (33.3%, chi(2) = 5.055, P = 0.025). The hypermethylation rate of RASSF1A promoter in the esophageal squamous cell carcinoma at advanced stages (stages III - IV) was 69.2%, significantly higher than that in the esophageal squamous cell carcinoma at early stages (stages I - II, 35.0%, chi(2) = 7.392, P = 0.007). The hypermethylation rates of RASSF1A promoter in the high, moderate, and low differentiation tumors were 61.5% (16/26), 46.2% (12/26), and 28.6% (4/14) respectively without significant differences among them (chi(2) = 4.053, P = 0.132). CONCLUSION: Abnormal methylation exists in the RASSF1A promoter in esophageal squamous cell carcinoma. The hypermethylation of RASSF1A promoter is related to lymph node metastasis and TNM stage.

Bone diseases in rabbits with hyperparathyroidism: computed tomography, magnetic resonance imaging and histopathology.

BACKGROUND: Hyperparathyroidism (HPT) occurs at an early age and has a high disability rate. Unfortunately, confirmed diagnosis in most patients is done at a very late stage, when the patients have shown typical symptoms and signs, and when treatment does not produce any desirable effect. It has become urgent to find a method that would detect early bone diseases in HPT to obtain time for the ideal treatment. This study evaluated the accuracy of high field magnetic resonance imaging (MRI) combined with spiral computed tomography (SCT) scan in detecting early bone diseases in HPT, through imaging techniques and histopathological examinations on an animal model of HPT. METHODS: Eighty adult rabbits were randomly divided into two groups with forty in each. The control group was fed normal diet (Ca:P = 1:0.7); the experimental group was fed high phosphate diet (Ca:P = 1:7) for 3, 4, 5, or 6-month intervals to establish the animal model of HPT. The staging and imaging findings of the early bone diseases in HPT were determined by high field MRI and SCT scan at the 3rd, 4th, 5th and 6th month. Each rabbit was sacrificed after high field MRI and SCT scan, and the parathyroid and bones were removed for pathological examination to evaluate the accuracy of imaging diagnosis. RESULTS: Parathyroid histopathological studies revealed hyperplasia, osteoporosis and early cortical bone resorption. The bone diseases in HPT displayed different levels of low signal intensity on T(1)WI and low to intermediate signal intensity on T(2)WI in bone of stage 0, I, II or III, but showed correspondingly absent, probable, osteoporotic and subperiosteal cortical resorption on SCT scan. CONCLUSION: High field MRI combined with SCT scan not only detects early bone diseases in HPT, but also indicates staging, and might be a reliable method of studying early bone diseases in HPT.

[mRNA expression of RASSF1A in esophageal squamous cell carcinoma and clinical significance thereof].

OBJECTIVE: To investigate the mRNA expression of the new tumor suppressor gene, RASSF1A, in esophageal squamous cell carcinoma and its biological value. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of RASSF1A in the tumor tissues, tissues near tumor, and normal tissues, all obtained during operation, from 66 esophageal squamous cell carcinoma patients. RESULTS: The deletion rates of RASSF1A mRNA expression were 42.4% (28/66), 15.2% (10/66), and 0 in the tumor tissues, tissues near tumor, and normal tissues respectively. The deletion rates of RASSF1A mRNA expression in patients with lymph node metastasis was 61.1%, significantly higher than that of the patients without lymph node metastasis (20.0%, chi(2) = 11.323, P < 0.01); The deletion rates of RASSF1A mRNA expression in the esophageal squamous cell carcinoma at the advanced stages (stages III - IV) was 61.5%, significantly higher than that in the esophageal squamous cell carcinoma at the early stages (stages I - II, 30.0%, chi(2) = 6.417, P < 0.01). The deletion rages of RASSF1A mRNA in the highly, moderately, and lowly differentiation tumors were 38.5% (10/26), 38.5% (10/26), and 57.1% (8/14) respectively, However, there was no significant association between the differentiation degree of tumor and the grade the deletion rages of RASSF1A mRNA (chi(2) = 1.576, P = 0.455). CONCLUSION: The deletion of the mRNA expression of RASSF1A, a tumor suppressor gene, may play an important role in the tumorigenesis and influences the prognosis of esophageal squamous cell carcinoma.

[T(1) carcinoma of the lung: characteristics of lymph node metastasis and its clinical significance].

OBJECTIVE: To investigate the frequency, distribution and features of lymph node metastasis in T(1) carcinoma of the lung, and to provide evidence for lymph node dissection. METHODS: Two hundred and fifteen patients with T(1) carcinoma of the lung underwent R2 surgery plus extended dissection of hilar, interlobular and mediastinal lymph nodes according to the mapping system developed by Naruke. RESULTS: 1 674 groups of lymph nodes were dissected. The metastatic rates of N(1) and N(2) were 11% and 6% respectively. Lymph node metastatic rates in carcinoma of the lung with maximum diameters less than 1.5 cm and between 1.6 cm approximately 3.0 cm were 5% and 8% respectively. N(1) and N(2) metastasis was not found in squamous cell carcinoma of the lung with a maximum diameter less than 1.5 cm. N(2) metastatic rates were 5% in squamous cell carcinoma 23% in adenocarcinoma and 3/9 in small cell carcinoma, the difference being significant (P < 0.01). 3/4 squamous cell carcinoma invaded only one group of N(2) nodes, but over 3 groups of lymph nodes were positive in 40% of adenocarcinoma. Saltatory metastasis accounted for 41% of N(2) metastasis. Fourteen percent of N(2)-positive tumors in upper lobes metastasized to the lower mediastinum, whereas 60% of N(2)-positive cancers in lower lobes invaded the upper mediastinum. CONCLUSIONS: The frequency of lymph node metastasis increases with the growth of tumors. Metastasis in adenocarcinoma occurs more frequently than in squamous cell carcinoma, but most common in small cell carcinoma. Tumors at any site can metastasize to the distant mediastinum. Except for squamous cell carcinoma with maximum diameter less than 1.5 cm which are likely to be cured without lymph node dissection, other types of T(1) carcinoma of the lung need extended lymph node dissection.