Objective To investigate the effect of PNS on malignant melanoma and the expression of connexin32 in melanoma. Methods The spontaneous and experimental lung metastasis models of B16 melanoma were used to investigate the inhibitory effect of PNS on tumor growth and metastasis. The expression of connexin in melanoma were detected by immunohistoehemistry. Results (1) PNS can obviously inhibit the growth of B16 melanoma. The inhibition rate of the 480mg/kg PNS group was 50. 85%. (2) PNS can obviously inhibit the lung metastasis of B16 melanoma. The number of tumor colonies in lung of the 240 mg/kg PNS group and 480 mg/kg PNS group were lower than that in the negative control group. ( 3 ) The expression of connexin32 in melanoma was detected by immunohistochemistry:PNS could up-regulate the expression of connexin32 in membrane of melanoma. Conclusion PNS can inhibit malignant melanoma growth and metastasis and could also up-regulate the expression of connexin32 in membrane of melanoma.

Objective Resveratrol can improve nonalcoholic fatty liver disease , but its action mechanisms remain unclear . This study aimed to investigate the protective effect of resveratrol against the free fatty acid ( FFA)-induced apoptosis of human hepatic L02 cells and its possible mechanisms . Methods Human hepatic L02 cells were incubated with FFA and resveratrol for 24 hours.The prepared cells were divided into a blank control , an FFA ( 2 mmol/L) , and a resveratrol group ( 50 μmol/L resveratrol +2 mmol L/FFA).After treatment, we measured the triglyceride (TG), glutathi-one (GSH), and malonaldchyde (MDA) contents and caspase3 ac-tivity in the hepatocytes , determined the apoptosis of the cells by flow cytometry , and detected the protein expression of silent information regulator 1 (SIRT1) by Western blot as well as the mRNA expressions of catalase (CAT), Mn superoxide dismucase (MnSOD), Bcl-2, and Bax by qRT-PCR. Results The TG content and caspase 3 activity in the hepatocytes were significantly increased in the FFA ([3518.±64.2] μmol/L and [5.97 ±0.78] U/g) and the resveratrol group ([201.1 ±60.1] μmol/L and [3.60 ±0.73] U/g) as compared with those of the blank control ([40.2 ±7.4] μmol/L and [2.56 ±0.49] U/g) (both P<0.05), but the caspase3 ac-tivity was markedly decreased in the resveratrol group in comparison with that of the FFA group (P<0.05).Both early and late apop-tosis rates of the hepatocytes were remarkably higher in the FFA ([6.75 ±0.81]%and [8.52 ±0.54]%) and the resveratrol group ([4.94 ±0.44]%and [6.52 ±0.61]%) than those in the blank control ([3.38 ±0.33]% and [2.72 ±0.19]%) ( both P<0.05), with statistically significant differences between the former two groups (P<0.05).The resveratrol group showed significant differences in the GSH content ([100.2 ±8.8] nmol/g), the MDA level ([2.36 ±0.82] mg/g), and the relative expression of SIRT1 (0.84 ±0.04) from the FFA group ([73.8 ±13.1] nmol/g, [3.77 ±0.92] mg/g, and 0.61 ±0.07) and the control ([113.7 ±13.8] nmol/g, [1.85 ±0.41] mg/g, and 0.90 ±0.02) (all P<0.05).The resveratrol group also exhibited statistically significant differences in the relative expressions of the MnSOD , CAT, and Bax genes from the FFA and control groups (P<0.05). Conclusion Resveratrol attenuates FFA-induced apoptosis of human hepatic L 02 cells by activating SIRT1 and reducing the oxidative stress of hepatocytes .

Objective To investigate the clinical effect and safety of tigecycline on in patients with complicated intra-abdominal infections. Methods 52 cases of patients with complicated intra-abdominal infection were selected and randomly divided into 2 groups.26 cases in the control group were given routine anti-infection treatment, and 26 cases in the treatment group were treated with conventional anti-infection combined with tigecycline.The CD molecules and NK cell level, serum lactate and procalcitonin levels, and the clinical efficacy and safety were compared after the treatment between two groups.Results The effective rate of control group ( 69.23%) was lower than the treatment group ( 92.31%) with statistical significance (P<0.05), the levels of CD3 +, CD4 +/CD8 +, CD4 +and NK cells of the treatment group after treatment were higher than the control group, the level of CD8 +was lower than the control group after treatment, procalcitonin and serum lactate levels were lower than the control group, with statistical significance ( P<0.05 ) , there was no difference in adverse reactions between the two groups.Conclusion Tigecycline could improve the therapeutic effect of complicated intra-abdominal infections, reduce the lactate and procalcitonin levels with high safety.

Objective: To study the risk factors for prevalence of acute myocardial infarction (AMI) in young and middle-aged population. Methods: A prospective cohort study was conducted in 110100 subjects at the age of (18-98) years who received physical examination in Kailuan Group from 2012-06 to 2014-10. Based on the limitations of male≤53 years and female≤63 years, a total of 62367 subjects were enrolled in our study. The subjects were followed-up for 2 years by the end point event of AMI to analyze the risk factors ofAMI occurrence. Results: According to AMI occurrence at the follow-up period, the subjects were divided into 2 groups: AMI group, n=56 and Control group, n=62152. Compared with Control group, AMI group had increased BMI, SBP, DBP and elevated blood levels of LDL-C, TG; AMI group also showed the higher ratios of subjects with the history of diabetes and taking anti-hypertension medication. Cox proportional hazard regression analysis indicated that age (RR=1.37), male (RR=60.54), LDL-C (RR=1.12), and TG (RR=5.93) were the risk factors forAMI occurrence in young and middle-aged population, allP<0.05. Conclusion: Age, male gender, blood levels of LDL-C, and TG were the risk factors for AMI occurrence in young and middle-aged population.

Objective:To investigate the independent correlation between serum IL-6 level and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) and to evaluate its predictive value for DCI.Methods:Consecutive patients with aSAH admitted to the Affiliated Hospital of Jining Medical University from June 2017 to June 2019 were enrolled retrospectively. They were divided into DCI group and non-DCI group according to the diagnostic criteria of DCI. Multivariate logistic regression analysis was used to determine the independent correlation between serum IL-6 and DCI. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum IL-6 level for DCI. Results:A total of 160 patients with aSAH were enrolled. They aged 66.1±8.1 years, and 98 were males (61.3%); 76 patients (47.5%) had DCI. Multivariate logistic analysis showed that after adjusting for smoking, hypertension, systolic blood pressure, hyperlipidemia, and drug treatment, serum IL-6 (the first quartile as a reference, and the third quartile: odds ratio[ OR] 3.885, 95% confidence interval [ CI]1.361-7.189; the fourth quartile: OR 9.706, 95% CI 3.412-18.344), Glasgow Coma Scale score ( OR 2.174, 95% CI 1.325-4.538) and Fisher grade ( OR 3.267, 95% CI 1.638-6.725) were independently associated with DCI. The ROC curve showed that the area under the curve of serum IL-6 for predicting DCI was 0.777 (95% CI 0.706-0.849), and the optimal cut-off value was 13.01 ng/L. The sensitivity and specificity of predicting DCI were 72.4% and 71.4%, respectively. Conclusions:Serum IL-6 is an independent risk factor for DCI after aSAH, and has certain predictive value for DCI.

Objective:To compare and analyze the effects of impulse oscillometry (IOS) and pulmonary function test (PFT) in the assessment of asthma control in children.Methods:A cross-sectional study of 323 children with bronchial asthma who visited the outpatient pediatric clinic of Shandong Provincial Hospital Affiliated to Shandong First Medical University from March to December 2020 was conducted.The patients were divided into the control group (123 cases) and the uncontrolled group (200 cases) according to the Childhood Asthma Control Test (C-ACT) score.In both groups, PFT and IOS were performed.The PFT test included the forced expiratory volume in one second (FEV 1), force expiratory volume in one second/forced vital capacity (FEV 1/FVC), peak expiratory flow (PEF), the instantaneous forced expiratory flow at 50% of forced vital capacity (FEF 50), the instantaneous forced expiratory flow at 75% of forced vital capacity (FEF 75), and maximum mid expiratory flow (MMEF). In the IOS test, the total respiratory impedance at 5 Hz (Z5), respiratory resistance at 5 Hz (R5), respiratory resistance at 20 Hz (R20), reactance at 5 Hz (X5), respiratory resistance at 5 Hz-respiratory resistance at 20 Hz (R5-R20), reactance area (AX), and resonance frequency (Fres) were measured.The data obtained were analyzed statistically using SPSS 25.0 software. ANOVA or Mann- Whitney U rank-sum test was used to compare data between groups.Receiver′s operating characteristic (ROC) curves were drawn to determine the predictive value of PFT and IOS parameters for uncontrolled asthma. Results:(1) According to the comparison results of PFT indexes between the two groups of children with asthma, the levels of FEV 1, FEV 1/FVC, PEF, FEF 50, FEF 75, MMEF in the control group were all higher than those in the uncontrolled group [(104.41±12.38)% vs.(98.89±16.61)%, 100.50 (94.40, 103.50)% vs.96.00 (89.83, 101.88)%, (100.29±15.31)% vs.(93.19±18.43)%, 85.60(70.60, 96.60)% vs.72.35 (57.08, 91.10)%, 67.20 (53.60, 81.70)% vs.56.80 (41.10, 74.73)%, 80.70 (66.80, 95.10)% vs.69.50 (54.03, 90.05)%] (all P<0.01). (2) According to the comparison results of IOS indices between the two groups, the levels of Z5, R5, R20, R5-R20, X5, AX and Fres in the control group were lower than those in the uncontrolled group {68.58 (63.29, 77.43)% vs.81.27(70.93, 91.96)%, 68.91(62.94, 77.60)% vs.80.61 (70.02, 89.29)%, 75.78 (67.50, 87.55)% vs.82.97 (71.50, 95.50)%, 0.51 (0.43, 0.59) [kPa/(L·S)] vs.0.62 (0.53, 0.74) [kPa/(L·S)], 69.31 (59.93, 79.14)% vs.86.48 (70.00, 102.48)%, 1.11 (0.76, 1.60) kPa/L vs.2.14 (1.42, 2.85) kPa/L, 18.21 (16.06, 19.56) Hz vs.20.56 (18.92, 22.81) Hz} (all P<0.01). (3) In the control group, 31 children (25.20%) had pulmonary dysfunction.(4) In the uncontrolled group, 95 children (47.50%) had pulmonary ventilation dysfunction.Only 20 children (10.00%) had a R5 larger than 120% of the predicted value and/or a R20 larger than 120% of the predicted value.(5) According to the ROC analysis results of the IOS indices for predicting asthma exacerbations, all of the areas under the ROC (AUC) of Z5, R5, R5-R20, X5, AX and Fres were greater than 0.7.AX had the highest value in predicting asthma exacerbations (AUC=0.785, 95% CI: 0.735-0.835), with sensitivity of 78.50% and specificity of 64.20%.All of the AUCs of PFT indices were smaller than 0.7.FEF 50 and MMEF had the largest AUC. Conclusions:PFT and IOS have good sensitivity in evaluating the level of asthma control in children, and IOS has good value in predicting asthma exacerbations.AX has the highest predictive value for asthma exacerbations.Asthma control levels of children should be evaluated using not only subjective (such as C-ACT score) but also objective (e.g.PFT, IOS) indices.

Articular cartilage superficial zone (SFZ) is the top layer of articular cartilage and its injuries are common in clinic.Therefore its find in time and conducting the treatment can delay the progress rate of os-teoarthritis (OA) and alleviate the pain and economic burden of the patients.At present,MRI is the most sen-sitive noninvasive examination technique to evaluate articular cartilage injury.Conventional MRI is limited in the early detection of subtle degeneration before cartilage morphological changes existence,and articular carti-lage lesions can only be detected when the injury is in an irreversible stage.In recent years,with the develop-ment of high field intensity MRI techniques such as 3T and 7T,the detection of water molecules,collagen fi-bers and tissue anisotropy in cartilage has considerable advantages,which can make the quantitative analysis and functional imaging for the ultrastructure and biochemical composition changes of SFZ in articular carti-lage.This article reviews the latest research progress on diagnostic value of MRI on articular cartilage SFZ and injuries.

Objective: To elucidate the association between large conductance calcium-activated potassium channels (BK_Ca) in the paraventricular hypothalamic nucleus (PVN) and sympathetic outflow in rats with chronic heart failure (CHF) . Methods: Male Wistar rats (6-7 weeks old) were randomized to sham operated group and CHF group (coronary artery ligation) . Two weeks after operation, BK_Ca inhibitor Iberiotoxin (IBTX) was infused into PVN by osmotic minipumps, rats were divided into following groups: sham+aCSF, CHF+aCSF, sham+low dose IBTX (0.125 nmol/nl) , CHF+low dose IBTX, sham+moderate dose IBTX (1.25 nmol/nl) , CHF+moderate dose IBTX, sham+ high dose IBTX (12.5 nmol/nl) , and CHF+high dose IBTX (n=6 each) . Additional rats were grouped as follows: sham+vehicle, sham+KCNMB4 knockdown (by rAAV2-KCNMB4 shRNA virus injection in PVN) , CHF+vehicle, CHF+ KCNMB4 knockdown group (n=6 each) . The cardiac function was determined by echocardiography, left ventricular hemodynamics were measured invasively, renal sympathetic nerve activity (RSNA) was recorded at 6 weeks after coronary artery ligation or sham operation. The contents of norepinephrine (NE) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in plasma were determined by enzyme-linked immunosorbent assay. The protein and mRNA expression of KCNMB4 in PVN were measured by immunofluorescence staining, Western blot, and real-time PCR, mRNA expression of BK_Ca in PVN was detected by real-time PCR. Results: Compared with the sham operation group, the cardiac function of the heart failure group was significantly reduced (P<0.05) , and the plasma NE and the serum NT-proBNP were significantly elevated (P<0.05) . The protein and mRNA expression of KCNMB4 in PVN were obviously down-regulated in CHF rats (P<0.05) . After perfusion of IBTX or KCNMB4 knockdown by microinjection of rAAV2-KCNMB4 shRNA virus,right ventricular weight/body weight and lung weight/body weight ratio as well as left ventricular end-diastolic diameter were increased and left ventricular ejection fraction was decreased (all P<0.05) , the sympathetic driving indexes was increased in sham rats, changes of these parameters further aggravated in CHF rats (P<0.05) . KCNMB4 knockdown further downregulated protein expression in PVN of CHF rats. Conclusion Downregulation and blunted function of BK_Ca in PVN may contribute to sympathoexcitation and deterioration of cardiac function in rats with chronic heart failure.

In this study, the current status for breast diseases in a region with high-incidence of cervical cancer were epidemiologically investigated. From March to August, 2009, 17618 women, from Wufeng area of Hubei province, China, were recruited to screen breast diseases by using breast infrared diagnostic apparatus. Other diagnostic methods, such as B-mode ultrasound, X-ray mammography, needle biopsy and pathological examination were, if necessary, used to further confirm the diagnosis. The screening showed that 5990 of 17618 cases (34.00%) had breast diseases, 5843 (33.16%) had mammary gland hyperplasia, 48 (0.27%) had breast fibroadenoma, 11 (0.06%) had breast carcinoma, and 88 (0.50%) had other breast diseases. The peak morbidity of breast cancer was found in the women aged 50-60 ages. The morbidity of breast cancer was significantly increased in women elder than or equal to 50 years old (n=8, 0.157%) in comparison with that in the subjects younger than 50 years old (n=3, 0.024%) (u=2.327, P<0.05). It was shown that the occurrence of breast diseases was concentrated in women aged 20-40 years, while the total morbidity reached its peak at the age of 30 years and then decreased sharply after age of 40. Compared with the patients elder than or equal to 40 years old (n=3289, 27.46%), the morbidity rate of breast diseases was significantly increased in women less than 40 years old (2648 cases, 47.18%; P<0.001). However, there was no significant difference in the morbidity of breast diseases between the age group of 20-29 years and that of 30-39 years (P=0.453), and both of them were high. There was no significant association between the morbidity of breast diseases and cervical cancer. Since the morbidity of breast diseases was higher among young women, more attention should be paid to the screening of breast diseases among young women for early diagnosis.

The standardized treatment of malignant tumor has always been the direction of continuous improvement of major medical institutions.In recent years,the basic research,prevention,screening and diagnosis and treatment level of gastric,gastroesophageal junction and esophageal cancer have been greatly improved,resulting in a significant improvement in the 5 years'survival rate of patients,but there are still great differences in the diagnosis and treatment level among different regions.Chinese gastric cancer,gastroesophageal junction cancer and esophageal cancer differ greatly from European and American countries in etiology,pathological types,high incidence sites,etc.Therefore,the relevant guidelines of European and American countries cannot fully meet Chinese clinical practice.In 2021,Elsevier Publishing Group launched the Chinese edition of Elsevier clinical pathway for gastric,gastroesophageal junction and esophageal cancer,and the first update edition was made in 2022,which aims to promote the quality control of tumor diagnosis and treatment,standardize tumor diagnosis and treatment behaviors,promote the homogenization and standardization of tumor diagnosis and treatment,and ultimately improve the survival rate and quality of life of patients with malignant tumor.This pathway refers to the National Comprehensive Cancer Network clinical practice guidelines,the Chinese Society of Clinical Oncology guidelines,combines evidence-based medicine and clinical experience,and follows the scientific,universal,standardized and operable principles.It has been promoted and applied in clinical practice,and is constantly updated according to the latest research results.