"Omics" and bioinformatics have brought new ideas to the study of traditional Chinese medicine. This study used metabonomics and network pharmacology to investigate the pharmacodynamic basis and regulation of Qishen Yiqi dropping pill (QDP) improving cardiac energy metabolism in rats with heart failure (HF). ¹H NMR metabonomics analysis showed that eight metabolites, including carnitine, glutamine, creatine, proline, homocitrulline, lactic acid, taurine and alanine appeared significant callback after QDP treatment for HF. The results indicate that QDP regulates the metabolism of carbohydrate, lipid, ATP and protein. The animal experiment was conducted in accordance with the regulations of the Ethics Committee for Experimental Animal Management and Animal Welfare of Institute of Materia Medica, Chinese Academy of Medical Sciences. A "drug-component-target-disease" network was established using network pharmacology, and the "component-target" sub-network related to the above energy metabolism processes was extracted by combining metabonomics results. Results revealed 79 chemical compounds and 47 potential targets of QDP involved in the regulation of energy metabolism, and identified key chemical components including ursolic acid, notoginsenoside G, ginsenoside-Rh1, and core targets such as INS, PPARG, and AKT1. The results also demonstrated the complex multi-target and multi-component relationship between QDP and HF from the perspective of energy metabolism. The molecular docking technique verified a strong interaction between some targets and chemical compounds, with affinities less than -5 kcal·mol^-1. The results of this study provide useful information for the clinical application, development, and utilization of QDP.

OBJECTIVE: To observe the early interventions of traditional Chinese Medicine (TCM) on the conversion time of nucleic acid in patients with coronavirus disease 2019 (COVID-19), and find possible underlying mechanisms of action. METHODS: A retrospective cohort study was conducted on 300 confirmed COVID-19 patients who were treated with TCM, at a designated hospital in China. The patients were categorized into three groups: TCM1, TCM2 and TCM3, who respectively received TCM interventions within 7, 8-14, and greater than 15 days of hospitalization. Different indicators such as the conversion time of pharyngeal swab nucleic acid, the conversion time of fecal nucleic acid, length of hospital stay, and inflammatory markers (leukocyte count, and lymphocyte count and percentage) were analyzed to observe the impact of early TCM interventions on these groups. RESULTS: The median conversion times of pharyngeal swab nucleic acid in the three groups were 5.5, 7 and 16 d (P < 0.001), with TCM1 and TCM2 being statistically different from TCM3 (P < 0.01). TCM1 (P < 0.05) and TCM3 (P < 0.01) were statistically different from TCM2. The median conversion times of fecal nucleic acid in the three groups were 7, 9 and 17 d (P < 0.001). Conversion times of fecal nucleic acid in TCM1 were statistically different from TCM3 and TCM2 (P < 0.01). The median lengths of hospital stay in the three groups were 13, 16 and 21 d (P < 0.001). TCM1 and TCM2 were statistically different from TCM3 (P < 0.01); TCM1 and TCM3 were statistically different from TCM2 (P < 0.01). Both leucocyte and lymphocyte counts increased gradually with an increase in the length of hospital stay in TCM1 group patients, with a statistically significant difference observed at each time point in the group (P < 0.001). Statistically significant differences in lymphocyte count and percentage in TCM2 (P < 0.001), and in leucocyte count (P = 0.043) and lymphocyte count (P = 0.038) in TCM3 were observed. The comparison among the three groups showed a statistically significant difference in lymphocyte percentage on the third day of admission (P = 0.044). CONCLUSION In this study, it was observed that in COVID-19 patients treated with a combination of Chinese and Western medicines, TCM intervention earlier in the hospital stay correlated with faster conversion time of pharyngeal swab and fecal nucleic acid, as well as shorter length of hospital stay, thus helping promote faster recovery of the patient. The underlying mechanism of action may be related to improving inflammation in patients with COVID-19.
Adult ; Aged ; COVID-19/drug therapy* ; Female ; Humans ; Length of Stay ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Retrospective Studies ; SARS-CoV-2

Studies have found that metformin is not only the preferred drug for lowering blood sugar, but also shows lipid-lowering and weight-loss effects. The purpose of this study was to use a hyperlipidemia hamster model to investigate the lipid-lowering effect of metformin and its effect on important metabolic pathways in lipid metabolism disorders. Fifty golden hamsters were divided into a control group, a model group, metformin high- and low-dose groups, and a simvastatin group. A high-fat diet was fed for 1 week to create the model, and then drug was administered for 11 weeks with the high-fat diet. Serum was taken for measurement of blood lipid and blood glucose at 2, 6, and 9 weeks after administration, and at weeks 3, 5, and 9 feces and urine were collected for ¹H NMR metabolomics tests. After 11 weeks of intravenous injection of [U-¹³C₆] glucose, serum was collected for a ¹³C NMR metabolic flux test. The results showed that the administration of metformin can significantly reduce blood lipids and glucose levels and can significantly affect metabolic pathways such as sugar metabolism, lipid metabolism, ketone metabolism, amino acid metabolism, and intestinal flora metabolism. The results of the metabolic flux analysis showed that the high-fat diet reduced the metabolism of tricarboxylic acids by 37.48%. After administration of low and high doses of metformin the metabolism of tricarboxylic acid increased by 98.14% and 143.10%, respectively. After administration of simvastatin tricarboxylic acid metabolism increased by 33.18%. The results indicate that metformin has a significant effect on promoting energy metabolism. This study used a combination of metabolomics and metabolic flow to explore the effect of metformin on lipid metabolism disorders and quantifies changes in the key pathway of energy metabolism-the tricarboxylic acid cycle. This study provides useful information for the study of the efficacy and mechanism of metformin, as well as a practical technical method for the screening of lipid-lowering drugs based on a hamster model.

Heart failure is the end stage of many cardiovascular diseases. It seriously affects the safety and quality of life of nearly 40 million people worldwide. At present, the clinical and pathophysiological characteristics of some types of heart failure are unknown, and there is no effective diagnosis and treatment. In recent years, genomics, transcriptomics, epigenomics, proteomics, metabolomics and other omics technologies have been widely used in disease research, providing new opportunities for the prevention, diagnosis and treatment of diseases. These strategies have also brought hope for the reduction in heart failure mortality. Based on the current status of clinical treatment of heart failure, this article reviews the roles and potential applications of these various omics technologies and their opportunities in the study of the pathogenesis of heart failure, clinical diagnosis and treatment, and related drug pharmacodynamics and mechanism of action.

Objective: This research aimed to explore the therapeutic effect and its mechanism of pirfenidone in liver cirrhosis induced by carbon tetrachloride in mice. Methods: Sixty male C57 BL/6 mice were randomly divided into the control group, model group and different doses of pirfenidone group, twelve rats in each group. Mice were intraperitoneally injected with 20％ CCl4 soybean oil solution ( 5 ml/kg), twice a week for 7 weeks. And these mice were free to drink 20％ ethanol solution in the third week after building the model. The low, medium and high dose groups were respectively given 50, 100 and 200 mg/kg of pirfenidone solution according to the body weights, while the model group and control group were given equal volume of blank solvent after building the model, once a day for 2 weeks. The serum level of ALT and AST, liver index, spleen index, the gene or protein expression level of TGF-β1 and Smad3 were analyzed before and after the treatment of pirfenidone. Results: The serum level of ALT, AST increased significantly in the model group ( P＜0. 05), while decreased significantly in different doses of pirfenidone group ( P＜0. 05). The liver and spleen index in the model group was significantly higher than that in the control group ( P＜0. 05). However, after treating with pirfenidone, the liver and spleen index were significantly lower than that in the model group ( P＜0. 05). The number of TGF-β1 positive cells in the model group was significantly more than that in the control group, but it was significantly decreased in the pirfenidone group. The gene expression level of Smad3 in the model group was significantly higher than that in the control group ( P＜0. 05). The gene expression level of TGF-β1 and Smad3 in different doses of pirfenidone group were significantly lower than that in the model group ( P＜ 0. 05). Meanwhile, the protein level of TGF-β1 and Smad3 were significantly increased in the model group, while decreased in the pirfenidone group. Conclusion: Pirfenidone relieves liver cirrhosis caused by carbon tetrachloride in mice by inhibiting the TGF-β1/Smad3 signaling pathway.

The aim of this study is to apply 3D printing technology to hospital drug dosing operations, and explore its feasibility and scalability. Drugs often dosed in hospitals are selected as models. The commercially available drug was ground into powder, diluted with medicinal excipients and then mixed with 75% ethanol and binder to prepare a paste for 3D printing. The dose and physicochemical properties of divided tablets were controlled by setting print parameters and printing models in computer software. Different 3D printers were employed to evaluate the impact of the device on the dosing tablet. Two drugs were dosed in this study to explore the scalability of 3D printing technology between different drugs. The drug content of the three divided dose tablets (warfarin sodium 1 mg, 2 mg, hydrochlorothiazide 5 mg) was 1.02±0.03, 1.96±0.01, 5.19±0.06 mg. The content uniformity was 1.0, 5.3, 2.6, respectively. The drug dissolution rate was (99.3±1.2)%, (101.5±0.3)%, (98.1±0.8)% in 45, 45 and 30 min. The mechanical properties of the three sub-doses and the stability within 30 days were in line with the Chinese Pharmacopoeia (2015) requirements. At the same time, it was found that the printing parameters and prescriptions can affect the properties of the divided dose tablets. By controlling the dilution ratio of commercial drug and printing parameters, the drug release rate can be customized to achieve individualized treatment. Both different modes of 3D printers can produce qualified sub-doses, and 3D print dispensing technology was also versatile between the two drugs. 3D printing can prepare small-volume, high-precision, high-repetition dosing tablets, with all properties in compliance with pharmacopoeia regulations. Thus, this method can be used as a new and scalable sub-dosing method.

OBJECTIVETo evaluate the performance of computer-assisted imaging system in the detection of cervical squamous intraepithelial lesion and quality-assurance.

METHODSManual PAP screening (n = 140 580) and image-assisted screening (n = 32 885) were compared for the detection rates of squamous cell abnormalities, the atypical squamous cells (ASC) to squamous intraepithelial lesion (SIL) ratio, the positive rates of high risk human papillomavirus (HR-HPV) test in the case of atypical squamous cells of undetermined significance (ASC-US), and the correlation between cytopathology and histopathology.

RESULTSCompared with manual screening, computer-assisted imaging system showed increased overall positive detection by 0.32%, decreased detection of ASC by 0.21%, increased detection of low-grade squamous intraepithelial lesion (LSIL) by 0.22%, increased detection of high-grade squamous intraepithelial lesion or worse (HSIL) by 0.31%, and decreased ASC to SIL ratio from 2.59 to 1.60. Computer-assisted imaging system did not change the HR-HPV positive rate of the patients who were ASC-US, or the coincidence rate between cytopathology and histopathology. Moreover, the productivity of the laboratory operation increased 58.33%.

CONCLUSIONComputer-assisted imaging system significantly increases the overall positive detection rate of cervical SIL, improves accuracy and work efficiency of screening, decreases the ASC/SIL rate, and strengths the quality-assurance of laboratory testing.

Carcinoma, Squamous Cell ; pathology ; Cervical Intraepithelial Neoplasia ; pathology ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Papillomaviridae ; isolation & purification ; Papillomavirus Infections ; pathology ; Uterine Cervical Dysplasia ; pathology ; Uterine Cervical Neoplasms ; pathology ; Vaginal Smears ; methods

OBJECTIVETo compare the short-term outcomes of surgical treatment for non-small cell lung cancer (NSCLC) by video-assisted thoracoscopic surgery (VATS) and open thoracotomy (OT).

METHODSData of 737 consecutive NSCLC patients who underwent surgical treatment for non-small cell lung cancer by video-assisted thoracoscopic surgery and 630 patients who underwent pulmonary resection via open thoracotomy (as controls) in Cancer Institute & Hospital, Chinese Academy of Medical Sciences between January 2009 and August 2011 were retrospectively reviewed. The risk factors after lobectomy were also analyzed.

RESULTSIn the 506 NSCLC patients who received VATS lobectomy, postoperative complications occurred in 13 patients (2.6%) and one patient died of acute respiratory distress syndrome (0.2%). In the 521 patients who received open thoracotomy (OT) lobectomy, postoperative complications occurred in 21 patients (4.0%) and one patient died of pulmonary infection (0.2%). There was no significant difference in the morbidity rate (P > 0.05) and mortality rate (P > 0.05) between the VATS group and OT group. In the 190 patients who received VATS wedge resections, postoperative complications occurred in 3 patients (1.6%). One hundred and nine patients received OT wedge resections. Postoperative complications occurred in 4 patients (3.7%). There were no significant differences for morbidity rate (P = 0.262) between these two groups, and there was no perioperative death in these two groups. Univariate and multivariate analyses demonstrated that age (OR = 1.047, 95%CI: 1.004 - 1.091), history of smoking (OR = 6.374, 95%CI: 2.588 - 15.695) and operation time (OR = 1.418, 95%CI: 1.075 - 1.871) were independent risk factors of postoperative complications.

CONCLUSIONSTo compare with the NSCLC patients who should undergo lobectomy or wedge resection via open thoracotomy, a similar short-term outcome can be achieved via VATS approach.

Age Factors ; Carcinoma, Non-Small-Cell Lung ; mortality ; pathology ; surgery ; Female ; Humans ; Length of Stay ; Lung Neoplasms ; mortality ; pathology ; surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Operative Time ; Pneumonectomy ; adverse effects ; classification ; methods ; Postoperative Complications ; etiology ; Respiratory Distress Syndrome, Adult ; etiology ; Retrospective Studies ; Smoking ; Thoracic Surgery, Video-Assisted ; adverse effects ; Thoracotomy ; adverse effects ; methods

OBJECTIVETo investigate the expressions of phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3β (p-GSK3β) and β-catenin proteins and to evaluate their relationship with the clinical pathological characteristics in epithelial tumors of the ovary.

METHODSThe expression of p-AKT, p-GSK3β, and β-catenin was detected with immunohistochemical staining (EnVision method) in 10 cases of benign epithelial neoplasia, 10 cases of borderline epithelial neoplasia and 70 cases of ovarian carcinoma. The relationship of the expression of p-AKT, p-GSK3β and β-catenin with the clinical pathological features was analyzed.

RESULTSThe positive expression rates of p-AKT, p-GSK3β and β-catenin in epithelial ovarian carcinoma were 67.1% (47/70), 60.0% (42/70) and 71.4% (50/70), respectively. Compared to the results of benign and borderline epithelial neoplasia, the expression of the three proteins in carcinoma of the ovary was significantly different (all P < 0.05).Positive correlation was found between p-AKT and p-GSK3β, p-GSK3β and β-catenin, and p-AKT and β-catenin in epithelial ovarian carcinoma (r = 0.546, 0.581, 0.500, respectively; all P < 0.05). Compared to the results of benign and borderline epithelial neoplasia, the expression of p-AKT protein in epithelial ovarian carcinoma was significantly different (all P < 0.05). The expression of p-AKT was correlated with the differentiation of epithelial ovarian carcinoma (P < 0.05), but no relationship was found between its expression and histological classification and FIGO staging (P > 0.05). The expression of p-GSK3β and β-catenin in epithelial ovarian carcinoma were both higher than that in benign and borderline epithelial neoplasia (P < 0.05), and correlated with tumor differentiation and FIGO staging (P < 0.05), but no relationship were found between their expression with histological classification (P > 0.05).

CONCLUSIONSPositive correlations are found between p-AKT, p-GSK3β and β-catenin in epithelial ovarian carcinoma. The activation of β-catenin is possibly correlated with inactivation of p-GSK3β that binds to p-AKT.

Adult ; Aged ; Carcinoma, Endometrioid ; metabolism ; pathology ; Cell Differentiation ; Cystadenocarcinoma, Mucinous ; metabolism ; pathology ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Cystadenoma, Mucinous ; metabolism ; pathology ; Cystadenoma, Serous ; metabolism ; pathology ; Female ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; Middle Aged ; Neoplasm Staging ; Ovarian Neoplasms ; metabolism ; pathology ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; metabolism ; beta Catenin ; metabolism

OBJECTIVETo compare the instructive value of the 6th and 7th editions of the UICC-AJCC staging system in prognosis of esophageal cancer (EC) patients.

METHODSThe staging and prognosis of 1397 esophageal carcinoma patients undergoing curative resection from Jan. 2003 to Dec. 2006 in our hospital were retrospectively reviewed and analyzed according to the 6th AJCC staging system and the 7th UICC-AJCC staging system.

RESULTSThe 5-year overall survival (OS) of EC patients with curative resection was 38.5% (481/1250 cases), with a follow-up rate of 89.5% (1250/1397 case). In overall terms, both the editions were statistically significant discriminators of OS (P < 0.05). The 5-year OS of stages I, II and III patients were 64.9%, 43.5%, 25.2% according to the 6th edition, and 63.5%, 44.5%, 23.5% according to the 7th edition, respectively. Distinct differences in survival were present among patients categorized as stage Ia and Ib according to the 7th edition (P < 0.05), with a 5-year OS of 80.0% and 58.3%, respectively. Similarly, according to the 7th edition, the 5-year overall survivals (OS) of the stages IIIa, IIIb and IIIc patients were 28.2%, 18.4% and 16.7%, respectively, showing that the prognoses were significantly different (P < 0.05). In addition, according to the 7th edition, the prognoses of patients in stages N0, N1, N2 and N3 were also significantly different (P < 0.01), and the 5-year OS were 50.0%, 31.5%, 18.7% and 16.7%, respectively.

CONCLUSIONSBoth the 6th and 7th editions of UICC-AJCC staging system are significant discriminators for survival of esophageal cancer patients. The 7th edition is proved to be more accurate in prognosis. The number of lymph node metastases is an important predictor of prognosis.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; classification ; pathology ; surgery ; Esophageal Neoplasms ; classification ; pathology ; surgery ; Esophagectomy ; methods ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; methods ; Retrospective Studies ; Survival Rate