Objective:To investigate the tumor suppressing effect of Shenqi Yiliu decoction combined with cisplatin via ERK-mediated C-Myc/PD-L1 phase-coordinated pathway on H22 hepatocellular carcinoma tumor-bearing mice and its mechanism.Meth-ods:In 60 SPF-grade male Kunming mice,10 mice were taken as blank group by random number table method,and the other 50 mice were replicated as H22 hepatocellular carcinoma tumor-bearing mouse model.After successful replication of the model,the model mice were randomly divided into model group,cisplatin group[2.5×10-3 g/(kg·3 d)],Shenqi Yiliu decoction low[13.515 g/(kg·d)],me-dium[27.03 g/(kg·d-1)],and high dose[27.030 g/(kg·d)]combined with cisplatin group[2.5×10-3 g/(kg·3 d)],10 mice in each group were treated for 13 d.After 24 h of the last dose,the mice were anesthetized and sacrificed,and the tumor inhibition rate,spleen index and thymus index of each drug group were determined;HE staining was performed to observe the histopathological changes of tumor in mice;ELISA kit was used to detect the contents of EGF and IFN-γ in tumor tissue homogenate;p-ERK1/2,C-Myc and PD-L1 protein expression in tumor tissue were detected by IHC and Western blot;ERK,C-Myc and PD-L1 mRNA expression levels in tumor tissue were detected by RT-PCR.Results:Compared with blank group,the average body mass and spleen index of mice in model group were decreased(P<0.05).Compared with model group,the tumor inhibition effect of each treatment group was obvious,and Shenqi Yiliu decoction combined with cisplatin group inhibited tumor growth in liver cancer mice in a dose-dependent way,im-proved the average body mass,spleen index and thymus index of mice,promoted the necrosis of tumor cells and increased the necrotic area.EGF and IFN-γ contents,P-ERK1/2,C-Myc,PD-L1 protein expressions and ERK,C-Myc,PD-L1 mRNA expression levels were decreased in tumor tissues(P<0.05).Compared with cisplatin group,the therapeutic effect of Shenqi decoction combined with cisplatin in medium and high dose groups was significant,and the difference was statistically significant(P<0.05).Conclusion:Shenqi Yiliu decoction combined with cisplatin effectively inhibited the tumor growth of H22 liver cancer tumor-bearing mice and significantly reduces the expression of C-Myc and PD-L1 proteins in the tumor tissues,which may be through the regulation of ERK signaling path-way-related protein expression to exert tumor suppressive effect.

ObjectiveTo investigate the tumor-suppressing effect of Shenqi Yiliu prescription combined with cisplatin in hepatoma H22-bearing mice based on the phosphatase and tensin homolog deleted on chromosome ten （PTEN）/phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt） pathway. MethodH22-bearing mice were prepared and randomized into model group， cisplatin group， and cisplatin combined with high-， medium-， and low-dose Shenqi Yiliu prescription groups， with 10 mice in each group. Another 10 healthy mice were randomly selected as normal group. Shenqi Yiliu prescription was given by gavage with the high， medium， low dose of 54.06， 27.03， 13.515 g·kg^-1·d^-1， respectively， and cisplatin （2.5 mg·kg^-1） was administered by intraperitoneal injection， twice a week. Normal group and model group received normal saline. After 13 days of treatment， mice were killed and the tumor inhibition rate was calculated. The pathomorphological changes of tumor were observed based on hematoxylin-eosin （HE） staining， and enzyme-linked immunosorbent assay （ELISA） and immunofluorescence method were used to detect the content of cyclin-dependent kinase inhibitor 1A （p21） and cyclin-dependent kinase inhibitor 1B （p27） in tumor tissue of mice. The levels of PTEN， PI3K and phosphorylated protein kinase B （p-Akt） in tumor tissue were measured by Western blot. ResultCompared with the model group， cisplatin alone and cisplatin in combination with the high-， medium-， and low-dose Shenqi Yiliu prescription decreased tumor mass （P<0.05）， particularly the cisplatin in combination with the high-dose Shenqi Yiliu prescription. Necrosis of the tumor tissue was observed in each group， especially the cisplatin combined with high-dose Shenqi Yiliu prescription group. As compared with the model group， cisplatin alone and cisplatin in combination with the high-， medium-， and low-dose Shenqi Yiliu prescription raised the expression of p21， p27， and PTEN （P<0.05） and lowered the expression of PI3K and p-Akt （P<0.05）， particularly the cisplatin in combination with high-dose Shenqi Yiliu prescription. ConclusionShenqi Yiliu prescription may regulate the expression of key molecules in PTEN/PI3K/Akt signaling pathway， thereby upregulating the expression of downstream proliferation inhibitors p21 and p27， further suppressing the tumor in H22-bearing mice， and enhancing the effect of chemotherapy.

Objective: To investigate neglect among preschool children in two-child families in southwest Shandong Province, and to provide reference is for improving nursing parenting quality of two-child families. Methods: A questionnaire survey was conducted among 2 646 parents of two-child families and 2 074 parents of one-child families from 16 kindergartens in southwest Shandong Province. Results: The total neglect rate of two-child family preschool children in southwest Shandong Province was 27.37%, and the degree score of neglect was(40.15±5.51). The physical neglect rate(10.39%), emotional neglect rate(40.15±5.51), total neglect (38.15±4.88) and emotional neglect (46.12±6.91) of boys were higher than those of girls, and the difference was statistically significant(χ2/t=4.57, 6.65, 4.58, 4.72, P<0.05); No significant frequencies were found in total neglect rate, total neglect, neglect rate and neglect at all levels among all age groups(P>0.05); Among preschool children with siblings aged 7-<13, ≥13, total neglect rate(30.44%, 32.77%), emotional neglect rate(10.20%,12.00%), total neglect degree (44.71±5.98, 45.33±5.20) and emotional neglect degree (45.95±7.12, 48.86±4.97) of preschool children in two-child families have higher than those in onechild families, and the differences were of statistical significance(χ2/t=31.10, 4.55, 27.92, 24.13, 19.83, P<0.05); the total neglect rate(27.37%), emotional neglect rate(23.47%), emotional neglect (43.68±6.83) of twochild families and the total neglect (40.15±5.51) were higher than those of one-child families, and the differences were of statistical significance(χ2/t=4.98, 4.96, 3.76, 8.53, P<0.05). The age of siblings(OR=0.58), the education level of mothers(OR=0.64), and the main executor of family education (OR=1.54) were main factors to influence the child neglect of preschool children in two-child families(P<0.05). Conclusion Neglect of preschool children in two-child families is higher than that in one-child families in southwest Shandong, especially among those preschool boys and preschool children whose siblings were of school age.

Ubiquitination is one of the most important post-translational modification processes in eukaryotic cells,in which the ubiquitin molecules and/or ubiquitin chains are covalently transferred to the substrate after a series of enzymatic cascade reactions involving the activating (E1),conjugating (E2) and ligating (E3) enzymes.Coupling to the 26S proteasome complex to form the Ubiquitin-Proteasome System (UPS),ubiquitination plays an essential role in controlling protein stability,thereby maintaining the dynamic balance of the key cellular proteins.Besides,ubiquitination is also involved in a wide range of protein degradation-independent events,such as gene transcription and translation,signal transduction,DNA repair and endocytoais,exerting a key function in response to exogenous stimuli and the cellular homeostasis.Similar to kinases,components of the ubiquitination system are often dysregulated,leading to a variety of diseases,such as cancer.Recently,accumulating evidence has shown an increasing number of dysregulated ubiquitination processes in osteosarcoma (OS).Herein,this review briefly provides current perspectives on the aberrance of ubiquitination-associated factors and their roles in OS,providing novel insight into potential therapeutic targets of OS.

The Internet Public Opinion Monitoring and Early Warning System for medical and health industry was designed and implemented due to the frequent occurrence of Internet public opinion, which has all-directional data collecting and analyzing functions, including big data collection, near duplicate detection, spam filtration, key public opinion early warning, region identification and tendency analysis, and can thus provide evidence for relevant departments to take effective measures for the control of Internet public opinion.

Aim To explore the effects of niacin on LDL-C uptake and metabolism in HepG2 cells,and to clarify the functions of niacin in lipid-lowering and slo-wing the atherosclerosis process,thus to provide a sci-entific basis for niacin as a lipid-lowering drug in clini-cal development.Methods Oil red O staining was used to observe HepG2 cells after lipid uptake.Enzy-matic method was used to determine the content of in-tracellular free cholesterol (FC)and total cholesterol (TC).The LDLR levels on the surface of cell mem-brane were detected by immunofluorescence flow cy-tometer.The mRNA and protein expressions of LDLR, SREBP2 and PCSK9 were analyzed by qPCR and Western blot.Results The results of oil red O staining showed that the rate of oil red O-positive cells and the number of red lipid droplets were significantly in-creased in niacin group than control group.Niacin sig-nificantly increased the levels of TC and FC in HepG2 cells(P <0.05 ).What’s more,niacin significantly upregulated the expression of LDLR and significantly downregulated the protein expression of PCSK9,while it had no effect on the expression of SREBP2.Conclu-sion Niacin accelerates LDL-C uptake probably via downregulating the expression of PCSK9 and reducing the degradation of LDLR protein in HepG2 cells.

Objective To investegate the effect of phosphorylated-P38 MAPK(mitogen-activated protein kinase) on the expression of caspase-3 in the substania nigra (SN) of MPTP-induced mouse model of(PD). Methods Mice were randomly divided into MPTP model group, which were treated with MPTP and inhibitor group. Once a day for 5 days; control group was treated with saline and DMSO as much as the model group received per day for 5 days. The behavioral were observed, immunohistochemistry and Western blot for TH, caspase-3 and phosphorylation of P38 MAPK were used to observe the change of positive cell number and the expression level in the SN of midbrain. Results Compared with the mice in control group, the model group showed typical symtoms of PD with decreased numbers of TH-positive neurons and the protein level of TH in SN of the midbrain by about 60% and 65% respec-tively(P<0.01) , the numbers of caspase-3 and phosphorylation of P38 MAPK immunoreactive cells and their protein level in the SN of the midbrain increased markedly (P<0.01). After giving SB203580, the above changes were reduced obviously (P <0. 01). Conclusion In the mouse model of subacute Parkinson's disease induced by MPTP, phosphorylated-P38 MAPK regulated caspase-3 in the SN of midbrain, the specific P38 MAPK inhibitor SB203580 is neurologically oprotective to the mouse model.

Objective:To investigate the expressions of Mfn2(mitofusin 2) in non-small-cell lung cancer (NSCLC) tissues and non-cancerous lung tissues,and analyze its relationship with clinicopathological characteristics of lung carcinomas.Methods:The expressions of Mfn2 mRNA and protein in 92 cases of NSCLC tissues and 27 cases of non-cancerous lung tissues were detected by in situ hybridization and immunohistochemical methods. Results:The positive rates of Mfn2 mRNA and protein in pulmonary squamous cell carcinoma were higher than those in adenocarcinoma (83.33% and 89.58% vs 56.82% and 65.91%), respectively. The positive rates of Mfn2 mRNA and protein in NSCLC were higher than those in the non-cancerous lung tissues (25.93% and 29.63%) . The difference was statistically significant among the three groups (P<0.001 and P<0.01). The expressions of Mfn2 mRNA and protein in well-differentiated (93.75% and 100%) and moderately-differentiated NSCLC (91.67% and 91.67%) were higher than those in poor-diffe-rentiated NSCLC (21.43% and 42.86%). The difference was significant (P<0.001). The expressions of Mfn2 mRNA and protein had no correlation with the gender, age, tumor size, TNM stage and lymph node metastasis (P>0.05). The expression of Mfn2 mRNA was consistent with that of Mfn2 protein in NSCLC.Conclusion:Mfn2 was involved in the initiation and progression of lung cancer, and the expression of Mfn2 was related to the histological types of lung cancer and its differentiation degree.

Objective To investigate the expression of hyperplasia suppressor gene(HSG)/mitofusin 2 (Mfn2)and P21 WAF1 in non-small cell lung cancer(NSCLC).Methods The expression of(HSG/Mfn2)and P21 WAF1 was detected in 92 cases of NSCLC samples by immunohistochemistry(SP).Results The absorptance value of the expression of HSG/Mfn2 in squamous cell carcinoma,adenocarcinoma,and non-cancer tissue were 15.06±2.73,12.21±2.96 and 10.36±3.60,respectively(P<0.05),and they were associated with tumor differentiation.The absorptanee valtue of the expression of P21 WAF1 in squamous cell carcinoma,adenocarcinoma,and non-cancer tissue were 3.16±0.98,3.44±0.22,0.06±0.32.The expression of P21 WAF1 in squamous cell carcinoma and adenocarcinoma Was higher than that in non-cancer tissue(P<0.05),and was closely associated with tumor differ-entiation and lymph node metastasis.Conclusion HSG/Mfn2,P21WAF1 is closely related to the pathogenesis and development of lung cancer.There is positive correlation between the HSG/Mfn2 and P2l WAF1 in lung cancer.

Objective To investigate the association between arterial stiffness of the common carotid artery(CCA)and insulin resistance in hemodialysis patients. Methods Arterial stiffness index β of CCA was evaluated by an ultrasonic phase-lock Echo-tracking system in 80stable non-diabetic hemodialysis patients.Insulin resistance was detected by the homeostasis model assessment method(HOMA-IR).Plasma hemoglobin,serum albumin,total cholesterol,high density lipoprotein,low density lipoprotein,triglyceride,lipoprotein(a),ApoA1,ApoB,CRP,calcium,phosphorus and creatinine were determined by standard methods. Results The stiffness index β was 11.41±4.13 in patients with previous cardiovascular disease(CVD)and 9.75±3.63 in those without CVD(P＜0.05).The stiffness index β was positively correlated with HOMA-IR(r=0.321,P＜0.01),as well as with age(r=0.376,P＜0.01),pulse pressure(r=0.267,P＜0.05),and duration of hemodialysis(r=0.219,P＜0.05).In stepwise multiple regression analysis,HOMA-IR(β=0.228,P＜0.05)and age(β=0.308,P＜0.01)were identified as significant independent variables for stiffness index β of CCA. Conclusions Insulin resistance is associated with aaefial stiffness in nondiabetic hemodialysis patients.The increased arterial stiffness may be the link between insulin resistance and cardiovascular morbidity as well as mortality in hemodialysis patients.