Objective:To study the relationship between circulating inflammatory proteins and liver cancer by Mendelian randomization.Methods:Data from the genome-wide association study (GWAS) of 91 circulating inflammatory proteins were sourced from the GWAS Catalog, involving 14 824 participants of European ancestry from 11 cohorts. Summary statistics for liver cancer were obtained from the GWAS database, encompassing a total sample of 197 611 cases, a two-sample Mendelian randomization analysis was conducted to evaluate the relationship between 91 circulating inflammatory proteins and liver cancer. Among them, inverse variance weighting, weighted median method, MR-Egger, simple mode, and weighted mode were the main analysis methods. Using odds ratio (OR) values to evaluate the causal relationship between them. Cochran Q-test, MR-PRESSO, MR-Egger intercept, and "leave-one-out" analyses were used for sensitivity analysis. Reverse MR, MR-Steiger tests were employed to rule out the influence of reverse causality.Results:Among the circulating 91 inflammatory proteins, C-C motif chemokine 20 ( OR=1.28, 95% CI: 1.01-1.62), CD40 receptor ( OR=1.31, 95% CI: 1.00-1.28), fibroblast growth factor 21 ( OR=1.47, 95% CI: 1.18-1.83), glial cell line-derived neurotrophic factor ( OR=1.29, 95% CI: 1.08-1.54), interleukin-13 (IL-13) ( OR=1.24, 95% CI: 1.02-1.50), IL-20 levels ( OR=1.78, 95% CI: 1.30-2.44), IL-20 receptor subunit alpha ( OR=1.43, 95% CI: 1.06-1.93), and matrix metalloproteinase-10 ( OR=1.21, 95% CI: 1.04-1.39) have positive causal relationship with the occurrence of liver cancer. And IL-1 alpha ( OR=0.83, 95% CI: 0.71-0.96), IL-24 ( OR=0.68, 95% CI: 0.47-0.99), leukemia inhibitory factor ( OR=0.77, 95% CI: 0.60-0.98) and stem cell factor ( OR=0.87, 95% CI: 0.78-0.97) showed negative causal relationship with the occurrence of liver cancer. Heterogeneity tests for all 12 circulating inflammatory proteins revealed no outliers. Sensitivity analyses consistently demonstrated robustness, with no evidence of pleiotropy observed. Neither reverse MR nor MR-Steiger tests supported the existence of a reverse causal relationship between inflammatory proteins and liver cancer. Conclusion:The C-C motif chemokine 20, CD40L receptor, fibroblast growth factor 21, glial cell line-derived neurotrophic factor, IL-13, IL-20, IL-20 receptor subunit alpha, MMP-10, IL-1 alpha, IL-24, leukemia inhibitory factor, and stem cell factor may be causally related to the development of liver cancer.

Based on the discussions in the The Inner Canon of Yellow Emperor （《黄帝内经》）， it is proposed that in the course of the disease， "bind" represents the initial stage of pulmonary nodules， while "accumulation" represents the final form. In terms of the pathogenesis， "two colds interacting" represented by "body cold" and "cold fluid retention" are the prerequisites for the formation of pulmonary nodules， while "disorder of qi" represented by "fainting" is the core of the formation. The specific manifestation is the disturbance of pivot of shaoyang （少阳） or shaoyin （少阴）， resulting in a complex of cold and heat， and then phlegm and stasis are suddenly generated and further formed into nodules. Therefore， the treatment principle should be to regulate the cardinal mechanism， dissolve phlegm and blood stasis. Depending on the complex degree of cold and heat， it is suggested to use Chaihu Guizhi Decoction （柴胡桂枝汤）， Chaihu Guizhi Ganjiang Decoction （柴胡桂枝干姜汤）， or Chaihu Xianxiong Decoction （柴胡陷胸汤） for disturbance of shaoyang pivot， while for shaoyin pivot dysfunction， modified Mahuang Fuzi Xixin Decoction （麻黄附子细辛汤） or Shengjiang Powder （升降散） can be used.

Objective:To evaluate the role of long non-coding RNA (lncRNA) NORAD in ketamine-induced neurotoxicity in mouse hippocampal neurons and the relationship with endoplasmic reticulum stress.Methods:Primary mouse hippocampal neurons were isolated and cultured and then divided into 5 groups ( n=36 each) using a random number table method: control group (group C), ketamine group (group K), ketamine+ pcDNA3.1-NORAD plasmid group (group K+ NORAD), ketamine+ control plasmid group (group K+ NC), and ketamine+ NORAD+ tunicamycin group (group K+ NORAD+ TM). Group C was cultured with normal medium for 24 h. Group K was cultured with 40 μmol/L ketamine for 24 h. Group K+ NORAD was transfected with pcDNA3.1-NORAD overexpressing plasmid for 48 h, followed by treatment with 40 μmol/L ketamine for 24 h. Group K+ NC was transfected with pcDNA3.1 (+ ) plasmid for 48 h, followed by treatment with 40 μmol/L ketamine for 24 h. Group K+ NORAD+ TM was transfected with pcDNA3.1-NORAD overexpressing plasmid, 24 h later endoplasmic reticulum stress activator tunicamycin 1 μg/ml was added and the neurons were cultured for 24 h, and then ketamine 40 μmol/L was added and the neurons were cultured for another 24 h. Cell viability was detected by CCK-8 assay. The amount of lactate dehydrogenase (LDH) released was analyzed. Cell apoptosis was determined by TUNEL and flow cytometry methods. The NORAD expression was detected by real-time polymerase chain reaction. The expression of endoplasmic reticulum stress-related proteins protein kinase R-like ER kinase (PERK), phosphorylated PERK (p-PERK) and C/EBP homologous protein (CHOP) was detected by Western blot. Results:Compared with group C, the cell viability was significantly decreased, the amount of LDH released, percentage of apoptotic neurons and apoptosis rate were increased, NORAD expression was down-regulated, CHOP expression was up-regulated, and p-PERK/PERK was increased in group K ( P<0.05). Compared with group K, the cell viability was significantly increased, the amount of LDH released, percentage of apoptotic neurons and apoptosis rate were decreased, NORAD expression was up-regulated, CHOP expression was down-regulated, and p-PERK/PERK was decreased in group K+ NORAD ( P<0.05), and no significant change was found in the parameters mentioned above in group K+ NC ( P>0.05). Compared with group K+ NORAD, the cell viability was significantly decreased, the amount of LDH released, percentage of apoptotic neurons and apoptosis rate were increased, CHOP expression was up-regulated, and p-PERK/PERK was increased ( P<0.05), and no significant change was found in the NORAD expression in group K+ NORAD+ TM ( P>0.05). Conclusions:Over-expressed NORAD can alleviate ketamine-induced neurotoxicity in mouse hippocampal neurons via inhibition of the endoplasmic reticulum stress.

Objective:To investigate the significance and mechanism of ten-eleven translocation (Tet1) against Mycobacterium marinum ( Mm) infection in mice. Methods:SPF wild-type C57BL/6 and Tet1-knockout (Tet1KO) mice were injected intravenously with Mm. All mice were monitored and the abscesses formed in tail were observed and quantified. Pathological changes in mouse tail tissues were observed using hematoxylin and eosin (HE) staining and transmission electron microscopy and the differences between the two groups were analyzed. Immunohistochemistry staining was used to detect the expression and distribution of TNF-α and TGF-β in mouse tail tissues. Moreover, mouse tail tissues were cultured on 7H10 plates for bacterial counting. The expression of NF-κBp65 and TGF-β was detected by Western blot. Results:Obvious lesions including abscesses and ulcers were formed in the Mm-infected C57BL/6, but only scattered small abscesses were observed in Mm-infected Tet1KO mice. During Mm infection, the bacterial load was gradually increased in C57BL/6 mice, but decreased in Tet1KO mice. Histopathological examination showed that obvious inflammatory cell infiltration and typical granulomatous lesions were found in Mm-infected C57BL/6 mice, while no significant inflammatory cell infiltration was detected in Mm-infected Tet1KO mice. Immunohistochemistry staining demonstrated that the expression of TNF-α and TGF-β was lower in Mm-infected Tet1KO mice than in Mm-infected C57BL/6 mice. Moreover, the expression of phosphorylated NF-κBp65 and TGF-β was significantly reduced in Mm-infected Tet1KO mice as compared with that in Mm-infected C57BL/6 mice. Conclusions:Deletion of Tet1 could alleviate the inflammatory damage mediated by Mm and enhance the host immune response to bacteria.

Objective To evaluate the diagnostic value of gray-scale ultrasound combined with contrast-enhanced ultrasound (CEUS) in thyroid imaging and reporting system ( TI-RADS) 3-5 nodules of American College of Radiology ( ACR) . Methods The 208 patients( 216 nodules) who underwent thyroid contrast-enhanced ultrasound examination from April 2014 to December 2016 were retrospectively analyzed . The ACR TI-RADS classification and contrast-enhanced mode of thyroid ultrasound were evaluated . The benign and malignant thyroid lesions were constructed through the analysis of contrast-enhanced mode of thyroid benign and malignant lesions in the past literature and the preliminary study of our group . Prediction model of gray scale combined with contrast-enhanced ultrasound for lesions were established . Besides ,the sensitivity ,specificity and accuracy of gray scale ultrasound combined with contrast-enhanced ultrasound prediction model for differential diagnosis of benign and malignant thyroid lesions were calculated based on the results of puncture biopsy or surgical pathology as the gold standard . Results Compared with pathological results , the positive predictive value , negative predictive value , accuracy , sensitivity and specificity of gray scale combined with contrast-enhanced ultrasound in evaluating thyroid nodules were 90 .8％ ,93 .3％ ,91 .2％ ,98 .8％ and 62 .2％ ,respectively . Conclusions Gray-scale ultrasound combined with contrast-enhanced ultrasound can provide clinical value in differential diagnosis of benign and malignant TI-RADS 3-5 thyroid nodules .

Objective To investigate the effect of stellate ganglion block ( SGB ) on early postoperative cognitive function in elderly patients undergoing orthopedic surgery .Methods 115 elderly patients with orthopedic surgery were selected as study objects ,and they were randomly divided into observation group (55 cases) and control group(60 cases) according to the digital table .The observation group received epidural anesthesia after SGB ,while the control group only received routine epidural anesthesia .Preoperation and postoperative 6h,3d and 7d,the mini mental state examination ( MMSE ) scores were measured and compared , the cognitive function was assessed .The MMSE score and postoperative cognitive dysfunction ( POCD) occurrence before and after surgery in the two groups were compared.Results In the observation group,the preoperative MMSE score was (29.36 ±2.54) points,the MMSE scores of 6h,3d and 7d after operation were (22.69 ±3.01) points,(25.33 ±2.69) points,(28.32 ± 3.04)points,respectively.The difference between preoperation and postoperation was statistically significant ( F =51.26,P <0.05).In the control group,the MMSE scores of before surgery and 6h,3d,7d after surgery were (29.69 ±2.17)points,(20.24 ±3.59)points,(21.87 ±2.02)points and (27.66 ±3.07)points,respectively,the difference was statistically significant (F=103.70,P<0.05).Before surgery,the MMSE score between the observa-tion group and control group had no statistically significant difference .6h and 3d after surgery,the MMSE scores of the observation group were higher than those of the control group (t=3.947,7.745,all P<0.05);7d after operation,the MMSE score between the two groups had no statistically significant difference (P>0.05).6h after surgery,the inci-dence rate of POCD of the observation group was 3.64％,which of the control group was 11.67％.3d after operation, the incidence rate of POCD was 1.82％ in the observation group and 3.33％ in the control group.There was no statistically significant difference in the incidence of POCD between the two groups at 6 and 3d after operation ( P>0.05).7d after operation,POCD was not detected in the observation group ,and the incidence rate of the control group was 3.33％.The total incidence rate of POCD was 5.45％ in the observation group and 18.33％ in the control group,and the incidence rate of the observation group was lower (χ2 =4.452,P<0.05).Conclusion SGB can improve the cognitive function of elderly patients after orthopedic surgery ,and it is worthy of clinical recommendation .

Currently,the BCG is used to prevent tuberculosis,but the immune effect is not ideal due to varied reasons.The existence of drug-resistant strains of tuberculosis and the increased prevalence and incidence of AIDS have leaded to the increased incidence of TB year by year.Therefore,the development of new tuberculosis vaccine is imminent In this paper,the latest research results in recent years for tuberculosis live vector vaccines were summarized,which provide a theoretical reference for further research and development of new TB vaccines.

Objective To obtain the recombinant corticotropin releasing hormone (CRH) protein with soluble, high purity protein through optimizing prokaryotic expression condition and purifying glutathione thiol transferase (GST)-CRH protein. Methods To detect the expression of soluble CRH protein through grope of the host strain GST-CRH temperature of induction expression, the host strain concentration (OD600), IPTG concentration and induction time, the purification of GST-CRH was performed by GST-CRH agarose gel. Western Blot assay was used for the expression identification of the target protein. Results The optimal conditions for the induction of CRH protein were determined: temperature of 30 ℃, IPTG induced concentration 0.1 mmol/L, bacteria density (OD600) 0.8, the induction time of 8 hours, purified GST-CRH>95% fusion protein was obtained. Conclusion The optimal expression conditions of GST-CRH are obtained, and the soluble protein of high purity GST-CRH is also obtained.

Objective To investigate the effect of high altitude hypoxia on chronic inflammation in rats.Methods Forty SD rats were randomly divided into 4 groups: control group (Con),chronic inflammation group (CI),high altitude hypoxia group (HH),high altitude hypoxia+chronic inflammation group (HH+CI).Rats in CI group were injected with lipopolysaccharide (LPS) (0.5 mg/kg) through the caudal vein twice a week for 4 weeks.Rats in HH+CI group were treated just as CI group was,but together with HH group rats were settled in a hypoxic environment of 6000 m altitude for three days.Pathological changes in lung tissues were observed by hematoxylin eosin stain.The peripheral white blood cell count and classification were measured.The levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in serum and lung tissues were detected by enzyme-linked immunosorbent assay (ELISA).Changes in IL-6 expression in rat lung tissues were observed by Western blotting.Results After LPS and high altitude hypoxia exposure,inflammatory cells infiltration and alveolar capillary expansion were observed in rats' lung tissue.Compared with Con group,not only the peripheral white blood cell count,but also the level of IL-6 and TNF-α in serum and lung tissue increased in CI and HH group(P<0.01).IL-6 expression levels observed by Western blotting were also increased in HH and CI group(P<0.01).High altitude hypoxia and chronic inflammation interacted(P<0.01).The peripheral white blood cell count was higher in HH+CI group than in other groups,and IL-6 and TNF-α expressions in lung tissue were increased(P<0.05).Conclusion An LPS-induced chronic inflammation model in rats is successfully obtained,and high altitude hypoxia could aggravate chronic inflammation.

OBJECTIVETo explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.

METHODSAccording to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.

RESULTSThe duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).

CONCLUSIONSIn patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cyclophosphamide ; administration & dosage ; adverse effects ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Incidence ; Induction Chemotherapy ; Lung Neoplasms ; drug therapy ; Neutropenia ; chemically induced ; epidemiology ; prevention & control ; Polyethylene Glycols ; Recombinant Proteins ; administration & dosage ; Taxoids ; administration & dosage ; adverse effects