Objective To investigate the expression of miR-6768-5p in lung cancer tissue and its effect on the proliferation and invasion of lung cancer cells through targeted regulation of carboxypeptidase A4(CPA4).Methods The expression of miR-6768-5p in lung cancer tissues and adjacent tissues was analyzed u-sing the TCGA database.Quantitative real-time PCR(qPCR)was used to detect the expression of miR-6768-5p in human lung cancer cell lines(HCC1588,H1650,H1299,A549,HCC827)and normal alveolar epithelial cells(HPAEpiC cells).Lung cancer cells were transfected with NC mimics and miR-6768-5p mimics,respec-tively,and divided into NC group and miR-6768-5p group.The MTS assay and Matrigel invasion assay were used to detect the cell proliferation and invasion ability of each group,respectively.The putative binding sites of miR-6768-5p and CPA4 were verified using RNAhybrid software and dual-luciferase reporter gene experi-ment.The expression of CPA4 mRNA in each group of cells was detected by qPCR.The expression of AKT/c-MYC signaling pathway proteins in the cells of each group was analyzed by Western blot.Results Com-pared with the adjacent tissues,the relative expression level of miR-6768-5p in lung cancer tissues was signifi-cantly decreased,and the difference was statistically significant(P＜0.05).Compared with HPAEpiC cells,the relative expression level of miR-6768-5p was significantly decreased in lung cancer cell lines,and the differ-ence was statistically significant(P＜0.05).Compared with the NC group,the cell proliferation rate of miR-6768-5p group was significantly decreased(P＜0.05).The number of invasive cells in NC group and miR-6768-5p group was(131.30±12.55)and(37.45±7.77),respectively,and the number of invasive cells in miR-6768-5p group was significantly lower than that in NC group(P＜0.05).The relative expression level of CPA4 mRNA in H1299 cells of miR-6768-5p group was significantly lower than that in NC group(t=4.93,P＜0.05).Compared with the NC group,the expressions of AKT/c-myC signaling pathway proteins p-AKT,p-mTORC1,XIAP,MDM2 and C-myC proteins in miR-6768-5p group were significantly decreased.Conclusion The expression of miR-6768-5p is decreased in lung cancer tissues,and miR-6768-5p may inhibit the activation of AKT/c-MYC signaling pathway by targeting CPA4,and reduce the proliferation and invasion ability of lung cancer H1299 cells.

OBJECTIVE To predict potential quality markers(Q-markers) in Yinhua Miyanling tablets based on fingerprinting and network pharmacology methods. METHODS HPLC fingerprints of 13 batches of Yinhua Miyanling tablets were established, and the similarity analysis was carried out using the "Chromatographic Fingerprint Evaluation System for Traditional Chinese Medicine" to identify the common peaks and attribute them. The fingerprints of Yinhua Miyanling tablets were investigated using chemometrics, cluster analysis, principal component analysis and orthogonal partial least squares discriminant analysis in combination with SPSS 26.0 and SIMCA 14.1 software to identify the major signature components responsible for the differences. The network pharmacology was used to screen and analyze the targets and pathways of Yinhua Miyanling tablets, construct a "drug-component-target-pathway" network diagram, and predict the Q-Marker and core targets of Yinhua Miyanling tablets. RESULTS HPLC fingerprint of Yinhua Miyanling tablets was established, and 27 common peaks including chlorogenic acid, mangostin, wild baicalin, lignocerin and quercetin were identified. Chemical pattern recognition analysis screened five components as differential markers for Yinhua Miyanling tablets. Five active ingredients, 20 core targets and 20 key pathways were screened by network pharmacology, showing that all five active ingredients could be used as potential Q-Markers. CONCLUSION The method is stable, accurate and feasible for screening five chemical components as potential Q-Markers for Yinhua Miyanling tablets. It provides a reference for the overall control of the quality of Yinhua Miyanling tablets, and also lays the foundation for further research on the mechanism of action of Yinhua Miyanling tablets.

Objective To investigate the effect and mechanism of shikonin on the proliferation,migration,invasion and apoptosis of human gastric cancer MGC803 cells.Methods The MGC803 cells in the logarithmic growth phase were randomly divided into the blank control group,shikonin group,shikonin+insulin-like growth factor-1(IGF-1)group,and shikonin+LY294002 group.Cells in the blank control group were cultured in drug-free medium,cells in the shikonin group were cultured in the medium containing shikonin with a final concentration of 10 μmol·L-1,cells in the shikonin+IGF-1 group were cultured in the medium containing shikonin with a final concentration of 10 μmol·L-1 and IGF-1 with a final concentration of 10 μmol·L-1,and cells in the shikonin+LY294002 group were cultured in the medium containing shikonin with a final concentration of 10 μmol·L-1 and LY294002 with a final concentration of 30 μmol·L-1.After 24 h of culture,the cell proliferation was detected by cell counting kit-8,the cell apoptosis was detected by flow cytometry,the cell migration was detected by scratch assay,and the cell invasion was detected by Transwell assay.The expression levels of B cell lymphoma-2(Bcl-2),Bcl-2 related X protein(Bax),cytochrome C(Cyt C),cleaved caspase-3,cleaved caspase-9,phosphoinositide 3 kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(PKB),and phosphorylated PKB(p-PKB)proteins were measured by using Western blot.Results The MGC803 cell proliferation inhibition rate and apoptosis rate in the shikonin group were significantly higher than those in the blank control group(P＜0.05);the MGC803 cell proliferation inhibition rate and apoptosis rate in the shikonin+IGF-1 group were significantly lower than those in the shikonin group(P＜0.05);and the MGC803 cell proliferation inhibition rate and apoptosis rate in the shikonin+LY294002 group were significantly higher than those in the shikonin group(P＜0.05).The MGC803 cell scratch healing rate and the number of invasive cells in the shikonin group were significantly lower than those in the blank control group(P＜0.05);the MGC803 cell scratch healing rate and the number of invasive cells in the shikonin+IGF-1 group were significantly higher than those in the shikonin group(P＜0.05);and the MGC803 cell scratch healing rate and the number of invasive cells in the shikonin+LY294002 group were significantly lower than those in the shikonin group(P＜0.05).The relative expression level of Bcl-2 protein in MGC803 cells in the shikonin group was significantly lower than that in the blank control group(P＜0.05),while the relative expression levels of Bax,Cyt C,cleaved caspase-3 and cleaved caspase-9 proteins and the Bax/Bcl-2 ratio were significantly higher than those in the blank control group(P＜0.05);the relative expression level of Bcl-2 protein in MGC803 cells in the shikonin+IGF-1 group was significantly higher than that in the shikonin group(P＜0.05),while the relative expression levels of Bax,Cyt C,cleaved caspase-3 and cleaved caspase-9 proteins and the Bax/Bcl-2 ratio were significantly lower than those in the shikonin group(P＜0.05);and the relative expression level of Bcl-2 protein in MGC803 cells in the shikonin+LY294002 group was significantly lower than that in the shikonin group(P＜0.05),while the relative expression levels of Bax,Cyt C,cleaved caspase-3 and cleaved caspase-9 proteins and the Bax/Bcl-2 ratio were significantly higher than those in the shikonin group(P＜0.05).The relative expression levels of p-PI3K and p-PKB proteins and the ratios of p-PI3K/PI3K and p-PKB/PKB in MGC803 cells in the shikonin group were significantly lower than those in the blank control group(P＜0.05),and there was no statistically significant difference in the relative expression levels of PI3K and PKB proteins in MGC803 cells between the shikonin group and the blank control group(P＞0.05);the relative expression levels of p-PI3K and p-PKB proteins and the ratios of p-PI3K/PI3K and p-PKB/PKB in MGC803 cells in the shikonin+IGF-1 group were significantly higher than those in the shikonin group(P＜0.05),and there was no statistically significant difference in the relative expression levels of PI3K and PKB proteins in MGC803 cells between the shikonin+IGF-1 group and the shikonin group(P＞0.05);and the relative expression levels of p-PI3K and p-PKB proteins and the ratios of p-PI3K/PI3K and p-PKB/PKB in MGC803 cells in the shikonin+LY294002 group were significantly lower than those in the shikonin group(P＜0.05),and there was no statistically significant difference in the relative expression levels of PI3K and PKB proteins in MGC803 cells between the shikonin+LY294002 group and the shikonin group(P＞0.05).Conclusion Shikonin can inhibit the proliferation,migration and invasion and promote the apoptosis of human gastric cancer MGC803 cells,which may be related to its inhibition of the PI3K/PKB signaling pathway.

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN).AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

Objective:To investigate the effect of lncRNA AC132217.4 on the proliferation and invasion of liver cancer MHCC97-H cells and its molecular mechanism.Methods:The TCGA database was used to analyze the differential expression of AC132217.4 in liver cancer tissue and adjacent tissue, and to analyze the relationship between the expression level of AC132217.4 and the overall survival of liver cancer patients. Transfection of pcDNA-AC132217.4 plasmid into MHCC97-H cells was defined as AC132217.4 group, transfection of pcDNA plasmid into MHCC97-H cells was defined as negative control (NC) group, respectively. The proliferation and invasion ability of MHCC97-H cells were detected by MTT method and Matrigel invasion assay. The binding site between AC132217.4 and miR-18a-5p was analyzed by starBase v2.0 software and dual luciferase reporter gene assay. Real-time quantitative PCR (RT-qPCR) detected the differential expression of miR-18a-5p in the two groups of MHCC97-H cells. The expression of epithelial-mesenchymal transition protein was detected by Western-blotting. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s), and t-test was used for comparison between the two groups. Results:Compared with adjacent tissues, the expression of AC132217.4 was down-regulated in liver cancer tissues ( P<0.01). Compared with liver cancer patients with low expression of AC132217.4, the overall survival of liver cancer patients with high AC132217.4 expression was longer ( P<0.05). The pcDNA-AC132217.4 plasmid significantly inhibited the proliferation of MHCC97-H cells ( P<0.05). The number of invasive cells in the NC group and AC132217.4 group were (131.30±12.55) and (37.45±7.77), respectively. The pcDNA-AC132217.4 plasmid significantly inhibited the invasive ability of MHCC97-H cells ( t=6.36, P<0.01). AC132217.4 directly complemented miR-18a-5p ( P<0.01). The expression of miR-18a-5p in MHCC97-H cells in AC132217.4 group (1.04±0.30) was significantly lower than that in NC group (6.13±0.75) ( t=6.27, P<0.01). Compared with the NC group, the expressions of epithelial phenotype proteins Cytokeratin and Claudin-1 in MHCC97-H cells in AC132217.4 group were up-regulated, while the expressions of mesenchymal phenotype proteins Vimentin, Slug and Snail were down-regulated. Conclusions:The expression of AC132217.4 is low in liver cancer tissue, and it is related to the overall survival of liver cancer patients. AC132217.4 might inhibit the proliferation and invasion of liver cancer MHCC97-H cells by sponge miR-18a-5p.

Cardiac arrest is the fourth stage of sudden cardiac death, which is characterized by the cessation of electrical activity in the heart, rapid circulatory and respiratory failure, and the prognosis is often poor. How to effectively predict cardiac arrest is the key and difficult point in the diagnosis and treatment process. In recent years, the research on the application of early warning scoring system in cardiac arrest has made continuous breakthroughs, from initially formulating a traditional scoring system containing only basic vital signs indicators according to a certain number of samples to continuously increasing and changing indicators, increasing the sample size, and formulating an improved scoring system with better sensitivity and specificity. Nowadays, with the continuous development of electronic information technology, machine learning technology is introduced into the formulation of scoring system, which breaks through the limitations of previous scoring system and has achieved good results in clinic. This article analyzes and compares the relevant research and cutting-edge progress of different early warning scoring systems at home and abroad, and summarizes the research results, gaps and shortcomings. Finally, combined with the relevant policies of graded diagnosis and treatment in China, this paper discusses the development and application direction of cardiac arrest early warning scoring system in the future.

The new oral anticoagulants (NOAC) dabigatran, rivaroxaban, apixaban, and edoxaban are widely used in clinical anticoagulation because of their fixed doses and superior safety. Studies have pointed out that there are large inter-individual differences in the pharmacokinetic parameters and response of NOAC, which may be related to the genetic polymorphisms of transporters and metabolic enzymes involved in in-vivo processes. This article reviews the influence of gene polymorphism on the pharmacokinetics and adverse reactions of NOAC, and provides directions for future research.

As an important promising biomarker, high frequency oscillations (HFOs) can be used to track epileptic activity and localize epileptogenic zones. However, visual marking of HFOs from a large amount of intracranial electroencephalogram (iEEG) data requires a great deal of time and effort from researchers, and is also very dependent on visual features and easily influenced by subjective factors. Therefore, we proposed an automatic epileptic HFO detection method based on visual features and non-intuitive multi-domain features. To eliminate the interference of continuous oscillatory activity in detected sporadic short HFO events, the iEEG signals adjacent to the detected events were set as the neighboring environmental range while the number of oscillations and the peak–valley differences were calculated as the environmental reference features. The proposed method was developed as a MatLab-based HFO detector to automatically detect HFOs in multi-channel, long-distance iEEG signals. The performance of our detector was evaluated on iEEG recordings from epileptic mice and patients with intractable epilepsy. More than 90% of the HFO events detected by this method were confirmed by experts, while the average missed-detection rate was < 10%. Compared with recent related research, the proposed method achieved a synchronous improvement of sensitivity and specificity, and a balance between low false-alarm rate and high detection rate. Detection results demonstrated that the proposed method performs well in sensitivity, specificity, and precision. As an auxiliary tool, our detector can greatly improve the efficiency of clinical experts in inspecting HFO events during the diagnosis and treatment of epilepsy.

OBJECTIVE: To investigate the prevalence and influencing factors of work-related musculoskeletal disorders(WMSDs) among workers in a cement plant. METHODS: A total of 196 workers in a cement plant were selected as study subjects using a judgment sampling method. A revised Musculoskeletal Injury Questionnaire was used to investigate the occurrence of WMSDs in workers in the past year. RESULTS: The detection rate of WMSDs in different parts of the body of workers in the cement plant was 18.4%-32.1%. The detection rates of WMSDs in all parts of the body from high to low was as follows: shoulder(32.1%), neck(30.6%), upper back(24.0%), ankle/foot(24.0%), lower back(23.5%), hip/thigh(22.4%), wrist/hand(21.4%), elbow(18.4%), and knee(18.4%). Multivariate logistic regression analysis results showed that keeping the neck in the same posture for a long time was a risk factor for neck WMSDs [odds ratio(OR)=2.29, P<0.05). Frequent turning around was a risk factor for WMSDs on the neck and lower back(waist)(OR were 3.06 and 3.32, P<0.05). Maintaining the same posture for a long time on the back was a risk factor for shoulder and upper back WMSDs(OR were 3.22 and 2.34, P<0.05). Hard work was a risk factor for shoulder and upper back WMSDs(OR were 2.60 and 2.58, P<0.05). Driving a vehicle was a risk factor for lower back(waist) and ankle/foot WMSDs(OR were 2.54 and 3.17, P<0.05). Carrying objects heavier than 20 kilograms and frequent overtime working were risk factors for ankle/foot WMSDs(OR were 3.03 and 2.54, P<0.05). CONCLUSION: The most frequent parts of the body having WMSDs in the cement production workers are shoulders and necks. Occupational factors(turning around or keeping the same posture of neck and back) are risk factors of WMSDs on shoulder and neck.

Objective To compare the clinical outcomes of selective artery (SAC) with main artery (MAC) clamping of robotic partial nephrectomy (RPN) in patients with early-stage (cTiN0M0) renal masses.Methods Between October 2016 and September 2018,a total of 343 cT1 renal mass patients receiving RPN with SAC (n =21) or MAC (n =322) in our center,were retrospectively analyzed.There were 13 males and 8 females in SAC group with a mean age of (53.1 ± 10.6) years old,mean tumor size of (2.5 ±0.7)cm,and mean R.E.N.A.L.score of 6.2 ± 1.5.There were 149 males and 173 females in MAC group,with a mean age of (51.6 ± 12.3) years old,mean tumor size of(3.5 ± 1.4)cm,and mean R.E.N.A.L.score of 7.9 ± 1.6.There was statistical significance between two groups in tumor size and R.E.N.A.L score(P ＜ 0.001).The group covariates were balanced through propensity score matching (PSM) using 1:2 nearest neighbor matching method.After matching,mean age,tumor size,R.E.N.A.L.score and preoperative eGFR in the SAC and MAC groups were (3.1 ± 10.6) vs.(52.7 ± 10.2) years,(2.5 ± 0.7) vs.(2.6±0.7) cm,6.2 ±1.5 vs.6.2 ±0.9,and (101.7 ± 19.8)vs.(101.6 ±20.3) ml/(min · 1.73m2),respectively (P ＞ 0.05).Perioperative outcomes and follow-up data were compared between the two matched groups.Results There was no significant differences resulted regarding operating time [(127.0 ±54.8)min vs.(130.0 ±49.9) min],blood loss[(166.0 ± 173.5)ml vs.(124.0 ± 101.0)ml],ischemia time [(18.9 ± 6.4) vs.(18.1 ± 5.8) min],hospital stay [(8.7 ± 3.4) d vs.(8.5 ± 2.5) d],incidences of complications (28.6％ vs.19.0％),surgical conversions (0 vs.2.4％),transfusions (4.8％ vs.2.4％) or positive surgical margin(0 vs.0) and malignant pathological outcomes(95.2％ vs.92.9％).The follow-up durations ranged from 3 to 24 months with a mean duration of 9.1 and 12.4 months in SAC and MAC,respectively.At the end of follow-up,the two groups had similar decrease in estimated glomerular filtration rate [(7.5 ± 17.2) ％ vs.(12.1 ± 18.2) ％,P =0.466],but the difference was statistically significant with ECT-GFR both of function reduction in the operated kidney [(21.6 ± 14.6) ％ vs.(38.4 ± 20.7)％,P =0.001] and in two kidneys [(2.5 ±16.4)％ vs.(14.8 ±20.0)％,P =0.002].Conclusions Robotic partial nephrectomy with selective vascular control lead to better postoperative renal function compared with main vascular clamped PN techniques and does not lead to a higher surgical risk following a strict patient selection criteria.