The retrieval and evaluation of evidence is the basis for the development of clinical practice guidelines for Chinese patent medicine. As traditional Chinese medicine has a different development trajectory and utilization characteristics from modern medicine， there is certain differences in terms of evidence composition， retrieval and integration.This paper discussed multi-source body of evidence on Chinese patent medicine based on modern evidence-based medicine and ancient medical literature， and summarized the retrieval strategy as well as the possible problems and solving methods. For different types of evidence on Chinese patent medicine， the corresponding evaluation tools have been recommended， and the order to integrate the evidence based on the quality of the evidence from high to low is suggested. Finally， a multi-source based evidence retrieval-evaluation-integration scheme for Chinese patent medicine has been formed， which will provide a methodological reference for practitioners in the development of clinical practice guidelines for Chinese patent medicine.

Tumor necrosis factor-α(TNF-α)is involved in the regulation of multiple biological processes such as the proliferation,invasion,migration,and chemotherapy resistance of hepatocellular carcinoma(HCC)cells through TNF receptor-mediated signaling pathways.At the same time,TNF-α also plays a role in inducing the apoptosis of HCC cells.Some TNF-α inhibitors have been shown to inhibit the progression of HCC and prolong survival time.At present,the potential mechanism of action of TNF-α in HCC remains unclear,and exploration of the interaction between TNF-α and HCC can help to determine the potential therapeutic targets for HCC.This article summarizes the latest research advances in the mechanism of action of TNF-α in HCC and introduces the possibility of targeting TNF-α as a treatment method for HCC,in order to provide a theoretical basis for the prevention and treatment of liver cancer and drug research and development.

Objective:To analyze the incidence and mortality of malignant tumors in Gansu Province and their changing trends from 2015 to 2018. Methods:Collect relevant data of malignant tumors in Gansu Province from 2015 to 2018,and calculate statistical indicators such as crude rates,age-specific rates,age-standardized rates,and cumulative rates(0-74 years old)stratified by gender,area,and age groups. Results:From 2015 to 2018,the crude incidence rate of malignant tumors in tumor registration areas of Gansu Province was 282.08/100 000(320.56/100 000 for male and 242.03/100 000 for female),and the age-standardized incidence rate by Chinese standard population in 2000(ASIRC)and the age-standardized incidence rate by Segi's world standard population(ASIRW)were 216.75/100 000 and 216.63/100 000,respectively.The crude mortality rate was 171.78/100 000(212.02/100 000 for male and 129.53/100000 for female),and the age-standardized mortality rate by Chinese standard population in 2000(ASMRC)and age-standardized mortality rate by Segi's world standard population(ASMRW)were 133.77/100000 and 131.65/100 000,respectively.The incidence and mortality of malignant tumors began to increase rapidly in the age group of 60-64 years,reached the peak in the age group of 80-84 years,and then decreased in the age group of≥85 years.The top 5 malignant tumors were gastric cancer,lung cancer,liver cancer,colorectal cancer,and esophageal cancer,with the top 10 malignant tumors accounting for 77.46%of all new cases;The top 5 deaths were gastric cancer,lung cancer,liver cancer,esophageal cancer,and colorectal cancer,with the top 10 malignant tumors accounting for 86.43%of all deaths. Conclusion:The burden of malignant in Gansu Province is still heavy.The incidence of tumors of the digestive systems,lung cancer and female breast cancer are still among the highest in Gansu Province.Primary prevention and secondary prevention approaches should be strengthened and cancer prevention and control models should be optimized according to the epidemological characteristics of malignant tumors,optimize cancer prevention and control models,in order to contribute to the implementation of healthy Gansu and healthy China strategies.

Silver nanoparticles (AgNPs) is known as one of the most valuable metal nanoparticles in antibacterial and anticancer application. AgNPs-resistant bacteria has been documented, but it is unclear whether cancer cells can also escape the anti-cancer effect of AgNPs. In this study, we aimed to investigate this phenomenon and its underlying mechanism. The antibacterial activity and cytotoxicity of AgNPs were measured in the presence of HeLa cell metabolites. The status of AgNPs in the system associated with metabolites were characterized by UV-Vis, Zetasizer Nano ZS, and transmission electron microscopy. Non-targeted metabolomics was used to reveal the metabolites components that bind with AgNPs. HeLa cells were injected intraperitoneally to establish the tumor-bearing mice model, and the stability of AgNPs in mice serum was analyzed. The results manifested that HeLa cell metabolites inhibited the anticancer and antibacterial effects of AgNPs in a dose-dependent manner by causing AgNPs aggregation. Effective metabolites that inhibited the biological activity of AgNPs were stable in 100 ℃, insoluble in chloroform, containing sulfur elements, and had a molecular weight less than 1 kDa in molecular weight. There were 115 compounds bound with AgNPs. In vitro experiments showed that AgNPs aggregation occurred only when the concentration of α-ketoglutarate (AKG) and glutathione (GSH) together reached a certain threshold. Interestingly, the concentration of AKG and GSH in HeLa cellular metabolites was 10 and 6 times higher than that in normal cervical epithelial cells, respectively, which explained why the threshold was reached. Furthermore, the stability of AgNPs in the serum of tumor-bearing mice decreased by 20% (P < 0.05) compared with the healthy mice. In conclusion, our study demonstrates that HeLa cells escaped the anti-cancer effect of AgNPs through the synergistic effect of AKG and GSH, suggesting the need to develop strategies to overcome this limitation.
Humans ; Animals ; Mice ; HeLa Cells ; Silver/pharmacology* ; Ketoglutaric Acids/pharmacology* ; Metal Nanoparticles ; Anti-Bacterial Agents/pharmacology* ; Glutathione ; Microbial Sensitivity Tests

Objective:To analyze the current situation and effect of mobile applications for physical activity management in China.Methods:In this systematic review, search terms such as “exercise”, “sports”, “exercise”, “physical activity” and “mobile health” were used to retrieve the applications for physical activity management in the IOS Application Store developed in mainland of China. Then the Mobile Application Rating Scale (MARS) and the Behavior Change Technology (BCT) were used to evaluate the quality of the applications and analyze the behavior change technologies that applications adopted. Moreover, a systematic review of relevant experimental studies was applied to summarize the effectiveness of the applications in promoting physical activity.Results:Total of 141 applications were included in this analysis, and 58 behavior change techniques in 16 categories were applied. The most frequently used 4 categories of BCT were behavior comparison (67.4%), repetition and substitution (67.4%), knowledge construction (67.4%), feedback and monitoring (58.2%). The overall objective quality score of MARS was 3.17±0.42, of which, the score of engagements, functionality, aesthetic design and information quality was 2.67±0.73, 3.75±0.54, 3.44±0.59 and 2.83±0.55, respectively. The number of BCT adopted in each application had a linear relationship with the application′s objective quality score in MARS ( B=0.023, 95% CI: 0.018-0.029) and user rating ( B=0.040, 95% CI: 0.019-0.060) (both P<0.001). A total of 4 articles were included to test the effects of techniques (i.e., physical activity behavior monitoring, physical activity planning and physical activity guidance) in 4 applications. The overall quality of the literatures was good. The main outcomes were physical activity duration (3 articles) and step count (1 article). Compared with those who did not use the application or only used the accelerometer to monitor physical activity, subjects who used the application to monitor physical activity had significant longer physical activity durations and step count (both P<0.05). Conclusions:The number, function and technology of physical activity management applications in China are abundant, but the quality of the applications is moderate. The number of BCT is an important factor in evaluating application′s quality, but its effect on behavior change is still not clear.

Humans ; Asthma/drug therapy* ; Biological Therapy

Objective To investigate the expression of Sema4D in peripheral blood T cells and serum of patients with hepatitis B cirrhosis and its correlation with clinical indicators. Methods A total of 20 patients with chronic hepatitis B (CHB), 68 patients with hepatitis B cirrhosis, and 20 healthy controls who attended The 940 th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army from October 2020 to November 2021 were enrolled. According to Child-Pugh class, the patients with hepatitis B cirrhosis were divided into Child-Pugh class A group with 24 patients, Child-Pugh class B group with 24 patients, and Child-Pugh class C group with 20 patients. After peripheral blood samples were collected to isolate serum and peripheral blood mononuclear cells (PBMCs), flow cytometry was used to measure the expression of membrane-bound Sema4D (mSema4D) + CD4 + T cells and mSema4D + CD8 + T cells in PBMCs, and ELISA was used to measure the expression of soluble Sema4D (sSema4D) in serum; their correlation with viral replication and liver inflammation markers was analyzed. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Mann-Whitney U test was used for further comparison between two groups; a Spearman correlation analysis was also performed. Results There were significant differences in the expression of mSema4D + CD4 + T cells and mSema4D + CD8 + T cells between the CHB group, the hepatitis B cirrhosis group, and the control group ( F =43.092 and 13.344, both P < 0.001), while there were significant differences between any two groups ( P < 0.05). The expression levels of mSema4D + CD4 + T cells and mSema4D + CD8 + T cells gradually decreased with increasing Child-Pugh class ( F =14.093 and 17.154, both P < 0.05), and there were significant differences between any two groups ( P < 0.05). The content of sSema4D was 1.54(1.42-1.71) ng/mL in the control group, 1.08(1.07-1.38) ng/mL in the CHB group, and 4.87(2.13-14.97) ng/mL in the hepatitis B cirrhosis group, with a significant difference between the three groups ( H =32.366, P < 0.001) and between any two groups ( P < 0.05). The content of sSema4D was 2.42(0.59-5.65) ng/mL in the Child-Pugh class A group, 4.92(2.75-12.73) ng/mL in the Child-Pugh class B group, and 14.18(4.59-18.43) ng/mL in the Child-Pugh class C group, with a significant difference between the three groups ( H =11.889, P =0.003) and between any two groups ( P < 0.05). In patients with hepatitis B cirrhosis, the level of sSema4D was positively correlated with the levels of alanine aminotransferase (ALT) and HBV DNA quantification ( r =0.294 and 0.430, both P < 0.05). Conclusion Sema4D is lowly expressed on T cell membrane and highly expressed in serum of patients with hepatitis B cirrhosis, and sSema4D may be involved in the development and progression of hepatitis B cirrhosis by affecting the levels of ALT and HBV DNA.

Objective To investigate the effect and mechanism of acteoside (ACT) in inhibiting epithelial-mesenchymal transition (EMT) in human hepatoma HCCLM3 cells by regulating the ERK1/2 pathway. Methods CCK-8 assay was used to detect the effect of hepatocellular carcinoma cell proliferation. The invasion and migration of HCC cells were detected by scratch and Transwell tests. The mRNA and protein expression levels of the ERK1/2 signaling pathway and EMT-related genes (E-cadherin and N-cadherin) were detected by real-time PCR and Western blot analyses. Results ACT reduced the activity of HCCLM3 cells and inhibited the proliferation of HCC cells, and the effects had certain correlation with drug concentration and time. ACT inhibited the migration and invasion process of HCCLM3 cells in a concentration-dependent manner. ACT downregulated the mRNA and protein expression of genes related to the ERK1/2 signaling pathway. It increased the mRNA and protein expression levels of the EMT-related gene E-cadherin but decreased those of N-cadherin. Conclusion ACT could inhibit EMT and the invasion and migration of HCCLM3 cells in human hepatoma, and the underlying mechanism is closely related to the downregulation of the ERK1/2 signaling pathway.

Objective:To assess maxillary sagittal and vertical as well as upper airway changes immediately after mini-screw assisted rapid maxillary expansion (MARME) in class Ⅲ patients.Method:A consecutive sample of 48 class Ⅲ patients with maxillary transverse deficiency who visited the Department of Orthodontics, School & Hospital of Stomatology, Wuhan University between January 2013 and March 2023 was retrospectively collected. The sample was comprised of 24 growing patients (cervical vertebra maturation, CVM 1-4) and 24 nongrowing patients (CVM 5-6). Cone-beam CT scans before (T0) and immediately after MARME (T1) were imported into Dolphin Imaging software, and then voxel-based superimposition was conducted on the basis of the anterior cranial base. Sagittal and vertical changes of the maxillary landmarks (A, ANS, PNS, UI and Spr), as well as upper airway changes after MARME were measured on multiplanar reconstruction views. Wilcoxon signed-rank test was employed to analyze the changes after MARME. Mann-Whitney U test was employed to compare the changes between growing and non-growing patients. Results:Some class Ⅲ patients exhibited significant maxillary sagittal and vertical changes immediately after MARME. The amount of changes in midpalatal suture was 4.03 (2.99, 4.87) mm in growing patients, significantly larger than that in non-growing patients [2.27 (1.49, 3.64) mm] ( U=3.18, P=0.001). In growing class Ⅲ patients, the forward changes of A, ANS, PNS, UI and Spr were 0.35 (0.06, 0.80), 0.48 (0.11, 0.88), 0.48 (0.13, 0.99), 0.53 (-0.33, 1.04) and 0.40 (0.03, 0.69) mm, respectively. Vertically, the downward changes of A, ANS, PNS, UI and Spr were 1.45 (0.99, 2.13), 1.18 (0.61, 1.95), 1.30 (0.91, 1.96), 1.20 (0.71, 1.83) and 1.30 (0.81, 1.73) mm, respectively. All changes were significantly different from 0 after treatment ( P<0.05). In nongrowing patients, PNS moved forward by 0.18 (-0.08, 0.39) mm while other sagittal changes were statistically insignificant ( P>0.05); vertically, the downward changes of A, ANS, PNS, UI and Spr were 0.90 (0.51, 1.39), 0.73 (0.41, 1.21), 0.70 (0.55, 1.08), 0.60 (0.36, 1.19) and 0.70 (0.55, 1.23) mm, respectively. Significant immediate increase of the nasopharynx volume and nasal width was obtained in both groups ( P<0.05), and the changes of oropharynx volume and minimum cross-sectional area (MCA) presented as statistically insignificant ( P>0.05). Conclusions:For growing class Ⅲ patients, besides transverse expansion, significant forward and downward changes of maxilla were obtained immediately after MARME. For non-growing patients, significant downward changes were observed, while sagittal changes were negligible. The nasopharynx volume increased in both growing and nongrowing class Ⅲ patients immediately after MARME, whereas, the changes of oropharynx volume and MCA presented as statistically insignificant.

Objective:To investigate the expression of Macrophage migration-inhibitory factors (MIF) in hepatocellular carcinoma (HCC) tissues and its interaction with ERK1/2 signaling pathway, so as to establish a theoretical basis for further studying the molecular mechanism of MIF promoting HCC.Methods:From February 2020 to August 2021, 52 cases of hepatocellular carcinoma (HCC) tissues based on hepatitis B cirrhosis (HBV-LC) and 52 cases of adjacent tissues in Tianjin Medical University Cancer Hospital and 940th Hospital of Joint Logistic Support Force of PLA were collected as the experimental group, including 39 males and 13 females, aged 35-65 years. And 20 cases of normal liver tissue were selected as the control group. Immunohistochemistry was used to detect the expression of MIF, ERK1/2 and p-ERK1/2 proteins in liver tissues of the two groups, and in situ hybridization was used to detect the expression of ERK1/2 nucleic acid in liver tissues of the two groups.HepG2 HCC cells and L-02 normal hepatocytes were co-cultured with different concentrations of rMIF, the expression and phosphorylation levels of ERK1/2 and JNK1 proteins in the two kinds of liver cells were detected by Western-blot, and the expression levels of ERK1/2 nucleic acids in the two kinds of liver cells were detected by RT-PCR. One-way ANOVA was used for measurement data and χ 2 test was used for counting data. Results:The expressions of MIF, ERK1/2, p-ERK1/2 and ERK1/2 mRNA were significantly increased in HCC and para-cancer tissues (the expression of MIF in HCC group was 78.8%, and that in adjacent group was 75.0%; ERK1/2 80.8% in HCC group and ERK1/2 71.8% in paracancerous group. The expression of p-ERK1/2 75.0 % in HCC group and 46.2% in paracancerous group were respectively detected. ERK1/2 mRNA was expressed in HCC group 76.9%, ERK1/2 mRNA expression in paracancerous group 78.8%), and the differences were statistically significant compared with normal liver tissues ( P<0.05), but there was no significant difference between HCC and para-cancer tissues ( P>0.05). The expressions of ERK1/2, p-ERK1/2 and ERK1/2 mRNA in HepG2 HCC cells were significantly increased with the increase of rMIF concentration, and the increase was most obvious when rMIF concentration was 200 ng/ml, and the difference was statistically significant compared with L-02 normal hepatocytes ( P<0.05). Conclusion:MIF, ERK1/2 and p-ERK1/2 are highly expressed in HCC tissues and HepG2 HCC cells, suggesting that MIF promotes the occurrence and development of hepatocellular carcinoma through ERK1/2 signaling pathway.