Background and purpose: Plumbagin is the main active components of traditional Chinese medicine of plumbago zeylanica. The present studies show that plumbagin has a killing effect on tumor cells. This study aimed to investigate the function and primary mechanism of plumbagin on invasion and metastasis of human liver cancer SK-hep-1 cells. Methods:With the treatment of plumbagin in vitro, cell proliferation and adhesion of SK-hep-1 cells were detected by MTS staining, cell cycle of SK-hep-1 cells were detected by lfow cytometry, the self-renewal and propagation abilities of SK-Hep-1 cells were conducted by colony formation assay , invasion in cells were performed using transwell invasion assay, and the p21 and MMP-2/9 mRNA levels were detected by real-time RT-PCR. Results:With the treatment of plumbagin, SK-Hep-1 cells proliferation was decreased with plumbagin concentration-dependency and the IC50 value of plumbagin in SK-Hep-1 cells was 22.04 mmol/L. The colony formation ability of SK-Hep-1 cells was decreased and the percentage of cells in G0/G1 phase was increased in a dose-dependent manner, as compared to control. The cell adhesion and invasion abilities were decreased. The real-time RT-PCR showed that p21 mRNA expression was increased and the MMP-2/9 mRNA was decreased. Conclusion:Plumbagin could suppress the proliferation and invasiveness of human liver cancer SK-hep-1 cells in vitro, and these effects may be by up-regulation of p21 and down-regulation of MMP-2 and MMP-9.

Objective To investigate the effects and possible mechanisms of nicorandil on lung injury of the collapsed lung in one-lung ventilation.Methods Twenty-four clean Japanese big-ear rabbits were randomly divided into sham group (group S) (two-lung ventilation + thoracotomy),negative control group (group C) (one-lung ventilation + thoracotomy + saline),nicorandil group (group N) (one-lung ventilation+thoracotomy+nicorandil) and antagonist group (group J) (onelung ventilation+ thoracotomy+ nicorandil+ glyburide) equally.Mechanical ventilation was implemented through self-made double-lumen endotracheal tube after intravenous induction through ear marginal vein.Intravenous maintenance medicine was infused by trace injection pump after anesthesia induction.Thoracic surgery was simulated through one-lung or two-lung ventilation determined by auscultation,bubble test and direct observation.Then wet and dry weight ratio (W/D) and content of MDA were measured after non-ventilatory lung was processed and preserved.The expression of Akt,p-Akt and NF-κB protein in non-ventilatory lung tissue were detected by Western-blot in all groups.Results In respects of W/D and content of MDA,the other three groups had significant differences compared with group S (P ＜ 0.05).It was significantly lower in group N than in group C (P ＜0.05),and it was significantly higher in group J than in group N (P＜0.05).The expressions of pAkt protein and p-Akt/Akt in group N were significantly higher than those in group S and group C (P＜0.05).Those of group J were significantly lower than group N (P＜0.05).Compared with group S,the expression of NF-κB protein in group C was significantly higher (P＜0.05).That of group N was significantly lower than that of group C (P＜0.05).But that in group J was higher than that in group N (P ＜ 0.05).Conclusion Nicorandil has a protective effect on the collapse and inflation of non-ventilatory lung in rabbits under one-lung ventilation,acting on mitoKATP through PI3K/Akt,and down-regulating NF-κB to reduce IR-induced lung injury.

Objective To investigate the effects of nicorandil on hypoxia-inducible factor (HIF)-1α mRNA and protein in lung tissue of one-lung ventilation.Methods Twenty-four clean New Zealand white rabbits were randomly divided into sham group (group S) (two-lung ventilation+thoracotomy),negative control group (group C) (one-lung ventilation + thoracotomy + saline),nicorandil group (group N) (one-lung ventilation+ thoracotomy+ nicorandil) and antagonist group (group J) (one-lung ventilation + thoracotomy + nicorandil + glibenclanide) equally.The implementation of mechanical ventilation depended on self-made double-lumen endotracheal tube after intravenous induction through ear marginal vein.Intravenous maintenance medicine was infused by trace injection pump after anesthesia induction.The implementation of thoracic surgery was simulated through one-lung and two-lung ventilation by auscultation,bubble test and direct observation.Group S was given anaesthesia only,no one-lung ventilation group S,the other three groups had single lung ventilation,and the drug was injected before the operation.Group N was infused nicorandil 100 ptg· kg-1 · h-1 before the implementation of single lung ventilation for 1 h.Group C was injected with the same amount of normal saline.Group J was intravenous infusion of glibenclamide 75 μg· kg-1 · h-1 and nieorandil 100μg · kg-1 · h-1 the implementation of single lung ventilation for 1 h.Then wet and dry weight ratio(W/D) and superoxide dismutase (SOD) activity were measured after non-ventilatory lung was processed and preserved.The expression of HIF-1α protein of non ventilatory lung tissue was detected by Western-blot in the four groups.The transcription of HIF-1α mRNA was detected by real-time quantitative real-time PCR (qRT-PCR) in all groups.Results W/D in groups C and J were significantly higher compared with that of groups S and N (P＜0.05).The activity of SOD in groups C and J was significantly lower compared with groups S and N (P＜0.05).The expression of HIF1α protein and transcription of HIF-1α mRNA in groups C,N and J were significantly higher than those in group S,and that of group N was significantly higher than those of groups C and J (P＜0.05).Conclsion Nicorandil has a protective effect on the collapse and inflation of non-ventilatory lung in rabbit with one-lung ventilation,reducing oxidative stress by SOD,acting on mito KATP and coming into play by up-regulation of HIF-1α.

Objective To investigate the role of interleukin-22 (IL-22)-regulated autophagy in hydrogen peroxide (H2 O2 )-induced hepatocarcinoma cell damage. Methods HepG2 cells were transfected with pEGFP-LC3 and then cultured in RPMI 1640 medium free of fetal bovine serum (FBS) or containing 1％ or 10％ FBS. These cells were pretreated with rapamycin or an autophagy inhibitor (3-MA) and then stimulated with recombinat human IL-22 (rhIL-22). GFP-LC3 puncta formation and autophagy signaling ac-tivation were measured. MTT assay was performed to detect cell viability. Results rhIL-22 significantly promoted GFP-LC3 puncta formation and LC3-Ⅱ expression in HepG2 cells treated with different stimulation protocols. The autophagy pathway inhibitor, 3-MA, dramatically suppressed the rhIL-22-activated autophagy signals. rhIL-22 attenuated H2 O2-mediated HepG2 cell death and that could be inhibited by 3-MA. Conclu-sion IL-22 promoted the activation of autophagy signaling pathways and alleviated H2 O2-mediated HepG2 cell damage.

Objective We aimed to investigate the effect of ferroptosis on Shenling Baizhu Powder,a compound prescription of Chinese herbal medicine,in improving testicular spermatogenic function in hyperuricemic mice with spermatogenic dysfunction. Methods Sixty BALB/c mice were randomly divided into normal group,model group,Shenling Baizhu Powder high-,medium-,and low-dose groups (20.14,10.07,5.04 g/kg,by gavage),and ferrostatin-1(Fer-1) group (0.8 mg/kg,by tail vein injection),with 10 mice each group. Except for the normal group,the other groups were intraperitoneally injected with potassium oxonate suspension[600mg/(kg·d)]for 7 days to establish the hyperuricemic model,and then the corresponding intervention was given for consecutive 14 days. Content of serum uric acid (UA),testicular Fe2+,reduced glutathione (GSH),malondialdehyde (MDA) and superoxide dismutase (SOD) activity were detected by biochemical method. Epididymal and testicular indices were measured. The spermatogenic function of testes was evaluated by eosin-hematoxylin staining. Sperm quality was detected by an automatic animal sperm analyzer. Prussian blue staining was used to detect iron deposition in testicular tissue. Immunohistochemistry was used to detect the related protein expressions of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4) in testicular tissue. Western blotting was used to detect the related protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1(HO-1)/GPX4 signaling pathway in testicular tissue. Results Compared with the normal group,the contents of serum UA,MDA,and Fe2+in the testis tissue of the model group were increased,the GSH content and SOD activity were decreased,the epididymal and testicular index,testicular spermatogenic function,sperm density and activity rate were decreased,and the iron deposition and ACSL4 protein expression in the testis tissue were increased. The expressions of kelch-like ECH-associated protein-1 (Keap1) and Nrf2 were increased. The expressions of nuclear Nrf2,HO-1,GPX4,and recombinant solute carrier family 7 member 11 (SLC7A11) protein were decreased (P<0.01). Compared with the model group,the above indexes in the Shenling Baizhu Powder groups and the Fer-1 group were improved to varying degrees (P<0.05,P<0.01). Conclusion Shenling Baizhu Powder can inhibit the ferroptosis of testicular cells through the Nrf2/HO-1/GPX4 signaling pathway,and improve the testicular spermatogenic function of mice with hyperuricemia spermatogenic dysfunction.

Objective:To investigate the regulatory effects of sphingosine kinase-2 (SphK2) on the function of activated astrocytes and the progression of experimental autoimmune encephalomyelitis (EAE) in mice.Methods:Primary mouse astrocytes were isolated from wild-type (WT) C57BL/6 mice and sphk2 gene knock-out ( sphk2 -/-) mice and stimulated in vitro with interleukin 17 (IL-17). Real-time PCR was used to measure the expression of inflammatory cytokines and chemokines at mRNA levels. Western blot and immunofluorescence were used to detect the expression of glial fibrillary acidic protein (GFAP) and the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3). An EAE mouse model was constructed using myelin oligodendrocyte glycoprotein 35-55 (MOG 35-55) polypeptide. Western blot was used to detect the expression of GFAP and p-STAT3 at protein level and real-time PCR was used to detect the expression of inflammatory cytokines and chemokines at mRNA level in spinal cords. Hematoxylin-Eosin (HE) and Luxol fast blue (LFB) staining were used to observe the changes in inflammatory cell infiltration and demyelination in spinal cords. Results:Compared with the WT group, the phosphorylation of STAT3 was obviously reduced in in vitro activated mouse astrocytes of sphk2 -/- mice, and the expression of inflammatory cytokines and chemokines including monocyte chemotactic protein 1 (MCP-1), TNF-α and IL-6 at mRNA level was also significantly decreased. Compared with the WT EAE group, changes in the above-mentioned cytokines and relative proteins in sphk2 -/- EAE mice in vivo were similar to those in vitro. Moreover, inflammatory cell infiltration and demyelination were significantly reduced in spinal cords of sphk2 -/- EAE mice. However, no significant difference in in vitro or in vivo GFAP expression was observed between WT and sphk2 -/- mice. Conclusions:SphK2 might regulate the function of reactive astrocytes through STAT3 molecular pathway, thereby regulating the production of inflammatory cytokines and chemokines and participating in the pathological process of EAE.

Objective:To select the relevant evidence of percutaneous pericardial drainage tube nursing and summarize the best evidence.Methods:Evidence-based questions were established based on PIPOST model. BMJ Best Clinical Practice, China Biology Medicine disc (CBM) , UpTodate, Cochrane Library, Joanna Briggs Institute Evidence-based Health Care Database, China Guide Network, British Guide Network, National Guide Line Clearing House (NGC) , PubMed, EMbase, Evidence-based Medicine (EBM) , Registered Nurses' Association of Ontario (RNAO) , The European Society of Cardiology (ESC) , American Heart Association (AHA) , Chinese Journal Full-text Database and Wanfang Database were conducted computer retrieval. The search time was from the establishment of the database to December 31, 2020. Two researchers respectively evaluated the quality of the included literature and extracted data and summarized and summarized the evidence that met the standards.Results:Finally, 12 articles were included, including 1 evidence summary, 2 systematic reviews, 1 systematic assesment, 2 guidelines, 1 expert consensus and 5 case series studies. Finally, 11 pieces of evidence were formed, including 6 themes such as drainage tube selection, puncture wound nursing, drainage flow control, flushing and sealing of the tube, observation and recording points, extubation indications and care.Conclusions:This study summarizes the best evidence for percutaneous pericardial drainage tube nursing, which provides evidence-based basis for improving the quality of percutaneous pericardial drainage tube care.

Objective:To establish a general method for the simultaneous determination of hydroxyphenyl esters and quaternary ammonium bacteriostatic agents in eye drops.Methods:The chromatographic analysis was per-formed on an Agilent C18 column(4.6 mm ×250 mm,5 μm)with 1％triethylamine solution(pH adjusted to 5.0 with phosphoric acid)as mobile phase A and methanol as mobile phase B.Gradient elution was performed at col-umn temperature of 40 ℃.The detection wavelength was 214 nm,the flow rate was 1 mL·min-1,and the injec-tion volume was 20 μL.Results:Methylparaben,ethylparaben,propylparaben,butylparaben,benzalkonium chlo-ride and benzalkonium bromide were 0.11-559.0,0.10-513.0,0.10-258.8,0.11-270.5,1.07-537.0 and 1.03-512.8 μg·mL-1,respectively.The linear range was good(r＞0.999).The average recoveries of meth-ylparaben,benzalkonium bromide and benzalkonium chloride were 104.7％(RSD=1.3％),102.6％(RSD=1.1％)and 100.9％(RSD=1.1％),respectively.The contents of bacteriostatic agent in 100 batches of eye drops from 36 varieties of 12 enterprises were determined,and the accurate results were obtained.Conclusion:This meth-od provides a reference for the content quality control and safety evaluation of bacteriostatic agents in eye drops.

Objective To analyze the risks and related influencing factors of early screening for lung cancer,and to study prognostic factors based on survival conditions,in order to ultimately provide baseline data for the prevention and treatment of lung cancer.Methods A cluster sampling method was used to select 40 to 75 year old registered residence residents in 10 districts and 6 counties of Zhengzhou City in 2020 as screening objects.Through voluntary participation and filling in evaluation questionnaires,high-risk groups of lung cancer were evalu-ated,and then three screening tests(tumor markers,low-dose spiral CT and lung function)were performed on high-risk groups.Finally,we will adopt an active and passive follow-up approach to collect information on diag-nosed lung cancer patients.Statistically describe the screening data and describe the epidemiological results of different characteristic populations;Using multivariate logistic regression method for statistical analysis,compare the differences in various results of different factors.Results 50128 cases of early screening for lung cancer in Zhengzhou City were evaluated in 2020,with a completion rate of 100.26%.The average age of the survey was(59.86±17.67)years old,and the gender ratio was 0.81∶1.The high-risk detection rate is 30.15%.Multivariate logistic regression analysis showed that males(smoking)(OR=5.43,95%CI:5.20～5.67),individuals with a history of tobacco exposure(OR=3.82,95%CI:3.67～3.98),first-degree relatives who had previously suffered from lung cancer(OR=12.06,95%CI:11.02～13.20),and other populations were more susceptible to lung cancer(all P<0.05).Conclusion Male(smoking),exposure to secondhand smoke,cancer in first-degree relatives,previous diagnosis of other tumors,symptoms of lung infection,"chest tightness,shortness of breath,and difficulty breathing in daily life",and"significant psychological trauma in the past 3 years"are independent risk factors for lung cancer,which should be given special attention and effective intervention measures should be taken.

ObjectiveTo observe the clinical efficacy and safety of Shugan Bushen Yulin Decoction （疏肝补肾毓麟汤， SBYD） in the treatment of asthenospermia and infertility with liver constraint and kidney deficiency. MethodsA multicenter， randomized， controlled clinical study was conducted in three hospitals in central China. Totally 95 patients with asthenospermia and infertility were controlled. According to random number table， the patients were divided into treatment group （47 cases） and control group （48 cases）. The control group was given vitamin E soft capsules （100 mg per time， twice daily） orally， and the treatment group was given SBYD （one dose daily， 30 min after breakfast and dinner， about 200 ml each time） orally. The course of treatment was 12 weeks in both groups. After the treatment， the sperm concentration， percentage of forward motile sperm （PR）， and percentage of total sperm activity， that is PR + percentage of non-progressively motile sperm （NP） were compared between groups， and the clinical efficacy was judged. Traditional Chinese medicine （TCM） syndrome score （inlcuding 6 single symptom scores and total symptoms score） and 21-item depression， anxiety， and stress scale （DASS-21） scores （including depression， anxiety and stress scores） were compared between the two groups before and after treatment. The patients were followed up for 6 months， and the pregnancy status of spouse between groups was compared. The occurrence of adverse events and vital signs during the trial were recorded for safety assessment. ResultsTwo cases in the treatment group and three cases in the control group dropped out. Finally， 45 cases in each group were included in the statistical analysis. The total effective rate was 86.67% （39/45） in the treatment group， significantly higher than 73.74% （33/45） in the control group （P＜0.05）. After treatment， PR and PR + NP significantly increased in both groups， and were much higher in the treatment group than in the control group （P＜0.05）. The scores of lumbar and knee soreness， emotional disturbance， cold sperm， chest and rib-side and lesser abdomen distension and pain， frequent sighing， and the total TCM syndrome score in the treatment group decreased after treatment （P＜0.05）； and except for cold sperm， the scores of other symptoms mentioned above as well as the total TCM syndrome score in the treatment group were lower than those in the control group （P＜0.05）. The scores of depression， anxiety and stress of DASS-21 in the treatment group decreased after treatment， and were lower than those in the control group （P＜0.05）. After 6 months of follow-up， the spouses of 5 patients in the treatment group and 3 patients in the control group got pregnant （P＞0.05）. No adverse events occurred in both groups during the treatment， and their vital signs were stable. ConclusionSBYD can obviously improve sperm vitality and effectively improve the clinical symptoms， anxiety and depression， and is safe in treating asthenospermia and infertility with liver constraint and kidney deficiency.