Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective:To investigate the myocardial protective effect of extracorporeal cardiac shock wave therapy (CSWT) combined with sulfur hexafluoride microbubble post-conditioning on myocardial ischemia-reperfusion injury (MI/RI) in rats, and to provide theoretical support for clinical treatment of MI/RI.Methods:A total of 32 male SD rats were randomly divided into 4 groups: sham operation group (Sham group), MI/RI group (IR group), CSWT group (IR+ SW group), and CSWT combined with sulfur hexafluoride microbubble treatment group (IR+ SW+ MB group), with 8 rats in each group. Therapeutic intervention was performed in IR+ SW group and IR+ SW+ MB group on the 1st, 3rd and 5th day after modeling. The left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) of the rats were measured by echocardiography before and after treatment. On the 7th day, myocardial fibrosis was assessed by Masson staining, and cardiomyocyte apoptosis was observed by TUNEL staining. The myocardial apoptotic proteins Bcl-2, BAX, Cleaved-Caspase-3 and Cleaved-Caspase-9 in the infarct boundary area were detected by Western blot. The differences of the above indexes among different groups were compared.Results:①There was no significant change in heart rhythm and heart rate among the groups before and after treatment, and there was no significant difference in heart rate ( P>0.05). ②The echocardiographic results after treatment showed that, compared with IR group, LVEDD and LVESD in IR+ SW group and IR+ SW+ MB group decreased in turn, while LVEF and LVFS increased in turn with significant differences between each two groups (all P<0.05). ③Compared with IR group, the degrees of myocardial fibrosis and apoptosis in IR+ SW group and IR+ SW+ MB group were alleviated in turn, and the relief in IR+ SW+ MB group was the most obvious. Quantitative analysis showed that compared with IR group, the proportions of cardiomyocyte apoptosis in IR+ SW group and IR+ SW+ MB group decreased in turn, and there were significant differences between each two groups (all P<0.05). ④The results of Western blot detection showed that compared with IR group, the levels of Bcl-2 in IR+ SW group and IR+ SW+ MB group increased in turn, while the levels of BAX and the activation level of Caspase-3 and Caspase-9 protein decreased in turn. These differences were all statistically significant between each two groups (all P<0.05) except for the activation level of Caspase-3 protein between IR+ SW group and IR+ SW+ MB group ( P>0.05). Conclusions:CSWT combined with sulfur hexafluoride microbubble therapy can improve left ventricular remodeling and left ventricular systolic function by inhibiting cardiomyocyte apoptosis.

Multidrug resistance （MDR） has been a main culprit behind the failure of chemotherapy in patients with malignant tumors and a major obstacle to improving the life quality and prolonging the survival of patients. Hepatocellular carcinoma cells， the innate drug-resistant cells， are generally insensitive to radiotherapy and chemotherapy. Moreover， as the early symptoms of hepatocellular carcinoma are atypical， most patients are diagnosed at the advanced stage， with short survival period and high recurrence rate. Thus， the sensitivity to chemotherapy drugs is decreased. This explains how MDR becomes one of the important reasons for the failure of primary hepatocellular carcinoma （PHC） treatment. Therefore， it is an urgent task to search for safe and effective chemosensitizers with little adverse effect in the research on the drug resistance of hepatocellular carcinoma. As Chinese medicine has been widely applied in the treatment of tumors， the mechanisms of compound Chinese medicine prescriptions， Chinese medicine injections， and single Chinese medicinal in reversing chemotherapy resistance in liver cancer have attracted the interest of scholars. According to previous reports， the mechanisms can be summarized as increasing intracellular drug concentration， influencing changes in enzyme activity， inducing apoptosis， reversing abnormalities in cellular signaling pathways， and regulating the tumor microenvironment. Traditional Chinese medicine reduces the chemotherapy resistance of hepatocellular carcinoma cells through multiple targets and multiple pathways， thereby improving the chemotherapy sensitivity of the cancer cells and enhancing the toxicity of chemotherapeutic drugs to hepatocellular carcinoma cells. Therefore， exploring the mechanism of MDR of hepatocellular carcinoma from the perspective of traditional Chinese medicine is important for reversing the MDR and is of great reference value for clinical treatment of hepatocellular carcinoma. However， there are few experimental types and adverse effects available. Thus， the multi-mechanism and multi-target experiments and clinical research should be carried out in the future.

Primary liver cancer has various potential causes and insidious onset, and its progression is affected by many factors. Immunotherapy and targeted drug therapy have been used as non-radical treatment methods for primary liver cancer, but they cannot achieve a satisfactory effect and may lead to drug resistance. In recent years, the wide application of 16s high-throughput sequencing and the in-depth studies of microbiology have revealed the key role of microorganisms in the development and progression of liver cancer. The association of the liver with oral and intestinal flora is gradually clarified, and the regulation of oral and intestinal flora has brought new treatment methods for the disease. This article reviews the microbial theory of the oral-gut-liver axis and its application and development in the treatment of primary liver cancer.

Objective:To construct a prediction model for the prognosis of breast cancer patients with long non-coding RNA expression characteristics.Methods:To construct a long non-coding RNA(LncRNA) model for predicting the prognosis of breast cancer patients.Methods Analyzing LncRNA expression profiles and clinical characteristics of 1 081 breast cancer patients in the cancer genome atlas (TCGA) database.Performing differential expression analysis and univariate analysis on 112 paired breast cancer and normal breast tissues′ transcriptome sequencing data in the TCGA database, and screened for differentially expressed (DELncRNAs) that significantly correlated with the prognosis of BRCA (To reduce batch effects, sequencing data has been normalized using the DESeq function). One thousand eighty-one breast cancer patients were randomly divided into two groups: training set (541) and validation set (540). Performing Cox proportional hazard regression using DELncRNAs and establishing a multi-LncRNA prognosis model in the training set, followed by proportional hazards assumption test(PH assumption test). Patients were divided into high-risk and low-risk groups based on calculated risk score.Kaplan-Meier method was used for survival analysis, and 540 patients′ data were used for validation.To evaluate the prognostic value of the model in patients with squamous cell carcinoma of the lung and hepatocarcinoma in TCGA database.Gene Set Enrichment Analysis (GSEA) was used to analyze the specific mechanism of lncrna affecting the survival of patients.Results:There were 2815 differentially expressed genes screened by transcriptome sequencing, 91 of which were significantly related to the prognosis of breast cancer patients ( P<0.05). Based on the Cox regression analysis of 91 delncrna expression data from 541 breast cancer patients in training set, a Cox proportional risk regression model was constructed based on 5 LncRNA (training set AUC=0.746, validation set AUC=0.650): AC004551.1, MTOR-AS1, KCNAB1-AS2, FAM230G and LINC01283, and PH assumption test( P=0.388). K-M survival analysis showed that the survival time of high-risk group was significantly worse than that of low-risk group (median survival time: 7.049 and 12.21 years, HR 0.367, 95% CI0.228-0.597, P<0.001), and the survival time of high-risk group was significantly shorter than that of low-risk group (median survival time: 7.57 and 10.85 years, HR 0.412, 95% CI0.214-0.793, P<0.001). Similar prediction results were also obtained in other cancer species of TCGA: lung squamous cell carcinoma ( HR 0.604, 95% CI0.383-0.951, P=0.007) and liver cell carcinoma ( HR 0.551, 95% CI0.307-0.987, P=0.011). GSEA results suggested that the expression patterns of the above five LncRNA were related to the cell cycle regulation of tumor cells. Conclusion:The prognostic model constructed based on expression profile of AC004551.1, MTOR-AS1, KCNAB1-AS2, FAM230G and LINC01283 can be used to predict the prognosis of breast cancer patients, which is helpful to further guide clinical treatment.

Objective To investigate the effects of different doses of T-2 toxin on the expression of cytokines cytokines and pathological changes in parental mice and their offspring. Methods One hundred female mice and 25 male mice (CD-1, SPF) were adapted for one week. After regular random mating, observation of vaginal suppository within the first 24 hours was as the 0th day of pregnancy. The pregnant rats were divided into high dose, medium dose, low dose and control groups according to body weight by a random number table(Feed: the doses of T-2 toxin were 1 200, 600, 300, and 0 μg/kg, respectively), with 16 - 18 rats in each group. The high, middle and low dose groups began to consume the poisoned feed on the 0th day of pregnancy, while the control group consumed the standard feed. After natural delivery, their offspring were continually treated the same way as their mother until the offspring reached adulthood. Serum levels of interleukin-1β (IL-1β) and interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), organ coefficient and pathological changes of articular cartilage were determined. Results The levels of IL-1β,IL-6 and TNF-α in the control, low, middle and high T-2 toxin groups during the pro-pregnancy of the middle-aged mice were [(219.56 ± 19.32), (136.89 ± 20.41), (210.49 ± 21.23), (207.41 ± 21.23); (192.73 ± 22.43), (136.25 ± 29.55), (187.43 ± 39.32), (232.48 ± 39.32); (1 303.02 ± 142.10), (1 072.60 ± 78.30), (1 065.03 ± 37.44), and (1 169.72 ± 104.18) ng/L], respectively. The differences between control and T-2 toxin treated groups were statistically significant (F = 17.124, 6.237, 7.670, P < 0.05). For further pairwise comparison,IL-1β and IL-6 in low dose group were significantly lower than those in control, middle and high dose groups (P < 0.05); TNF-α content in control group was significantly higher than those in low,middle and high dose groups(P<0.05).There were significant differences in the levels of IL-1β,IL-6 and TNF-α between the control group and the low,middle and high dose groups of offspring weanling mice[(142.36 ± 13.36),(113.01 ± 8.65), (102.13 ± 8.31), (123.42 ± 10.41); (109.92 ± 9.76), (100.26 ± 15.60), (85.25 ± 9.97), (100.21 ± 16.46);(1 308.45 ± 204.90), (1 248.60 ± 96.85), (1 081.09 ± 105.51), (1 204.87 ± 153.96) ng/L, F = 49.823, 10.530, 7.490, P < 0.05]. The levels of IL-1β and IL-6 in the control group were significantly higher than those in the low, middle and high dose groups(P < 0.05).The levels of TNF-α in the control group were significantly higher than those in the medium and high dose groups(P < 0.05).The levels of the three cytokines IL-1β, IL-6 and TNF-α in adult filial mice were significantly different [(69.71 ± 9.61), (61.31 ± 10.07), (63.07 ± 10.39), (58.56 ± 9.69); (172.55 ± 24.55),(146.91 ± 13.47),(151.02 ± 24.93), (157.21 ± 17.86); (1 136.87 ± 137.39), (1 002.22 ± 86.52), (987.12 ± 130.80),(1 047.21 ± 171.64)ng/L, F=4.670,5.636, 4.775, P < 0.05], the contents of the three cytokines in the poisoning groups were significantly lower than that of the control group (P < 0.05). The organ coefficients of thymus, spleen and liver in the second trimester were significantly different [(0.14 ± 0.03), (0.20 ± 0.06), (0.15 ± 0.02), (0.12 ± 0.03); (0.71 ± 0.16), (0.78 ± 0.14), (0.77 ± 0.15), (0.38 ± 0.10); (6.19 ± 0.43), (5.57 ± 0.57), (6.04 ± 0.32), (5.11 ± 0.29), F = 4.056, 11.064, 8.312, P < 0.05], and the thymus index was significantly increased in low dose group (P<0.05),spleen coefficient decreased significantly in high dose group (P < 0.05), and liver coefficients in low and high dose group were significantly decreased (P < 0.05). In the offspring, the midbrain coefficient of viscera showed significant changes [(3.45 ± 0.73), (3.11 ± 0.31), (2.98 ± 0.45), (3.04 ± 0.22), F = 7.529, P < 0.05], which was significantly decreased in the exposed rats(P<0.05).Both the mid-pregnant mice and filial mice showed varying degrees of changes in epiphyseal cartilage injury. The degree of epiphyseal cartilage injury became higher with increasing dosages of T-2 toxin in mid-pregnancy and post-weaning parental mice, and the injury was more serious in post-weaning mice. Conclusions Exposure to T-2 toxin can cause decrease of cytokines IL-1β, IL-6 and TNF-α in the blood of CD-1 pregnant and filial mice, and also cause the cartilage damage in mice, which are aggravated following increased doses of T-2 toxin and extension of exposure time.

OBJECTIVE: To analyze the characteristics of newly diagnosed pneumoconiosis in gem processing industries in Guangdong Province from 2006 to 2016.METHODS: Data from Direct Reporting System for Occupational Disease Network in the gem processing industries in Guangdong Province from 2006 to 2016 were collected and analyzed according to pneumoconiosis disease category, regions, industry and enterprise characteristics.RESULTS: There were 202 new diagnosed pneumoconiosis cases in gem processing industry in Guangdong Province from 2006 to 2016,which showed a general decline trend after peaking in 2008.Among 202 cases,192 cases( 95.0%) were silicosis,9 cases( 4.5%) were other pneumoconiosis,1 case( 0.5%) was welder pneumoconiosis; 143 cases( 70.8%) were stage Ⅰ pneumoconiosis,44 cases( 21.8%) were stage Ⅱ pneumoconiosis,15 cases( 7.4%) were stage Ⅲ pneumoconiosis; 196 cases( 97.0%)were male and 6 cases( 3.0%) were female.The mean age for diagnosis was( 36.3 ± 0.4) years,and the median dust exposure duration was 9.6 years.There was 86.1% of cases centered at the Pearl River Delta region and 94.6% of cases working in jewelry and related goods manufacture industry,which were more commonly from Hong Kong,Macao,Taiwan and private own economy enterprises( 94.1%),as well as large and small enterprises( 72.2%).There was 38.2%( 21/55) of the enterprises reporting 2 or more cases,of which 3 enterprises had more than 10 new cases.The job titles of these cases were mainly drilling,cutting,sculpturing and stone cutting.CONCLUSION: The prevalence of pneumoconiosis in gem processing industries in Guangdong showed a decreasing tendency, but there is a potential risk of group onset of pneumoconiosis.The prevention and control procedures for dust hazard should be strengthened in gem processing industries.

Objective To analyze the correlation of serum estradiol (E2),testosterone (T),estradiol/testosterone (E2 /T) ratio and BMD(Bone mineral density), bone turnover markers in postmenopausal women, and then to provide a theoretical basis for the pathogenesis of postmenopausal osteoporosis.It might point to a new diagnostic indicator for postmenopausal osteoporosis (PMOP).MethodsFrom October 2014 to September 2016, 283 cases of postmenopausal women were recruited from the Renmin Hospital of Wuhan University.Bone mineral density was measured by dual energy X-ray absorption apparatus, and the recruiters were classified into three group: normal controls (95 cases), osteopenia (94 cases) and osteoporosis group (94 cases).Serum calium (Ca),alkaline phosphatase (ALP),and propetide of type-Ⅰ procollagen (PINP) and β C-terminal cross-linked telopeptide of type I collagen (β-CTX) were detected by Roche cobas 6000 analyzer.Serum E2 and T were measured by Siemens Advia Centaur XP analyzer.All statistical analyses were carried out using SPSS 15.0 software.Results Compared with the normal controls, Serum E2[(22.65±5.35)pg/ml vs (18.64±6.18 )pg/ml,(17.04±6.73) pg/ml,P<0.01]and E2/T ratio (9.03±3.21 vs 7.44±1.78,6.67±1.50,P=0.01) were significantly decreased in the group of osteopenia and osteoporosis.But the bone turnover marker PINP was significantly increased[(38.92±19.23) ng/ml vs (43.94±15.52) ng/ml,(46.28±19.21) ng/ml,P=0.04].Correlation analysis results showed that serum E2 and E2/T ratio was negatively correlated with PINP (r=-0.273,P<0.05;r=-0.284,P<0.05),but positively associated with total hip BMD(r2=0.053,P=0.001;r2=-0.136,P<0.001).Multiple linear regression analysis showed serum E2 and E2/T ratio could explain 17.6% and 28.9% of the total hip BMD variance after adjustment for age, BMI and years after menopause.The area under curve (AUC) of combined E2 and E2/T as a indicator for the diagnosis of PMOP was 0.824 (95% CI:0.765-0.884,P<0.01), which was significantly better than that of E2 or E2/T (P<0.01) only.Conclusions Serum E2 and E2/T ratio was negatively correlated with PINP, but positively associated with total hip BMD.The decrease of serum E2 and E2/T ratio showed a strong association with PMOP.The combined detection of E2 and E2/T is expected to be a valuable indicator for the prediction of PMOP and to monitor the process of osteoporosis.

Objective To screen the genes most relevant to lymph node metastasis of cervical cancer and identify the genes at the key knots of the regulatory network to provide the potential targets for cervical cancer intervention.Methods The transcriptional profiling database of TCGA was used, and random forests algorithm was adopted to rank the genes related to lymph node metastasis extracted from GeneCards database.STRING and Cytospace tolls were used to build the interactive regulatory network and identify the most weighted genes localized in the central of the network.DAVID platform was used to perform a functional annotation for the whole geneset.Results We ranked 2784 genes in respect to their potential contributions to lymph node metastasis of cervical cancer and identified the genes at the key knob.The genes related to cancer metastasis were enriched to cytokines pathway, MAPK pathway, wnt pathway, intercellular interaction, adhesive conjunction, cellular skeleton regulation, etc.Some of the identified key genes, like EGFR, NOTCH1, RHOA, etc. have been verified to be closely related cervical cancer metastasis in the basic and clinical research. Conclusion Random forests algorithm is useful, taking advantages of TCGA database, in enriching the genes playing significant role in cervical cancer metastasis.A majority of the genes in the analyzed geneset were indicated to be significantly correlated with lymph node metastasis.

Objective To observe the antitumor activity of sedum lineare thunb(SLT) and it′s affection on antioxidation and tumor immunology in S180‐bearing mice .Methods S180‐bearing mice model were established by subcutaneously inoculating S180 ascitic tumor into the right armpit .From the second day ,the mice were treated with normal saline ,cyclophosphamide (50 g/kg) or two doses of SLT (4 ,8 g/kg) through intragastric administration ,and the process extent 14 d .After the last administration ,the mice body weight and the index of tumor ,spleen and thymus were calculated ,classification of white blood cells in peripheral blood was tested ,and the activity of SOD and GSH‐Px as well as the content of MDA and NO in serum were measured .Results The body weight of mice treatmented with SLT was dramaticlly higher than those of the CTX (P< 0 .05) .Compare with the model group ,SLT groups showed decreases in tumors index (P<0 .05) ,spleen index (P<0 .05) ,percentage of peripheral blood neutro‐phil (P<0 .05) and monocyte (P<0 .05) ,and increases in thymus index (P<0 .05) and percentage of lymphocyte (P< 0 .05) . The activity of SOD and GSH‐Px and NO level in the SLT groups mice′s serum were significantly higher than those of the model group (P<0 .05) ,while the content of MDA in the SLT groups mice′s serum was markedly lower than those of the model and CTX groups(P<0 .05) .Conclusion SLT has antitumor activity in S180‐bearing mice bysuppressing oxidative stress and modula‐ting tumor immune .