Objective:To investigate the effect and mechanism of 6-formylindolo[3,2-b]carbazole (FICZ) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.Methods:Male C57BL/6J mice aged 8-12 weeks were divided into 4 groups with 8 mice in each group, according to the method of simple random sampling. Sepsis-induced ALI mice model was established by intraperitoneal injection of LPS 5 mg/kg (LPS group), and phosphate buffer saline (PBS) control group (PBS group) was injected with equal volume of PBS. The LPS+FICZ group was intervened by intraperitoneal injection of 1 μg FICZ 1 hour after LPS stimuli, while the FICZ control group (FICZ group) was given the same amount of FICZ 1 hour after intraperitoneal injection of PBS. Serum and lung tissue were collected 24 hours after LPS stimuli, and the pathological changes of lung tissue were analyzed by hematoxylin-eosin (HE) staining and wet/dry weight (W/D) ratio of lung tissue. The concentrations of inflammatory factors in serum and lung tissue were detected by enzyme linked immunosorbent assay (ELISA). The expression levels of endoplasmic reticulum stress signaling pathway related molecules were detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) and Western blotting.Results:Compared with PBS group, inflammatory cell infiltration, alveolar collapse and obvious alveolar exudative lesions had increased, lung tissue W/D ratio was significantly increased, serum interleukin-6 (IL-6) level, lung tissue IL-6 mRNA expression, and the mRNA expressions of glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), CCAAT/EBP homologous protein (CHOP), and the protein expressions of GRP78, PERK, activating transcription factor 6 (ATF6), CHOP in lung tissue were significantly increased in LPS group. However, the indexes of FICZ group were not affected. Compared with LPS group, LPS+FICZ group had less inflammatory cell infiltration, relatively intact alveolar structure. Lung W/D weight ratio in LPS+FICZ group was significantly decreased (5.38±0.10 vs. 6.60±0.30, P < 0.01), so as serum IL-6 (ng/L: 15.55±3.77 vs. 32.22±3.84) and lung IL-6 mRNA expression (2 -ΔΔCt: 0.79±0.21 vs. 6.89±0.92, both P < 0.01). The mRNA expressions of GRP78, PERK and CHOP were also significantly decreased [GRP78 mRNA (2 -ΔΔCt): 1.90±0.16 vs. 7.55±1.29, PERK mRNA (2 -ΔΔCt): 1.68±0.20 vs. 4.54±0.89, CHOP mRNA (2 -ΔΔCt): 1.13±0.24 vs. 4.44±1.13, all P < 0.05], and the protein expressions of GRP78, PERK, ATF6 and CHOP were significantly decreased (GRP78/GAPDH: 0.59±0.02 vs. 0.77±0.01, PERK/GAPDH: 0.48±0.03 vs. 1.04±0.05, ATF6/GAPDH: 0.51±0.03 vs. 0.65±0.01, CHOP/GAPDH: 0.91±0.05 vs. 1.11±0.07, all P < 0.05). Conclusion:FICZ protects LPS-induced ALI possibly via suppressing endoplasmic reticulum stress and reducing IL-6 expression in blood and lung tissue.

Objective To perform the ligand-based computer-aided drug design and construct the pharmacophore model of(1,3)-β-D-Glucan Synthase(GS)small molecule inhibitors.Method Six small molecules with diverse structures and good inhibitory activity were selected to construct the training set.The HipHop algorithm in Catalyst pharmacophore generation module was utilized to construct the pharmacophore models.The pharmacophore models were evaluated by constructed Decoy-set 3D database.Results Pharmacophore 02 has a good enrichment factor,sensitivity and specificity parameters.Pharmacoph-ore model validation with Decoyset 3D database proved that the model has good distinguishing capability.Conclusion The pharmacophore model of GS small molecule inhibitors was constructed and tested.It will provide valuable information for de-sign and discovery of novel small molecule GS inhibitors.

Objective:To investigate the relationship between serum leukocyte-associated immunoglobulin-like receptor 2 (LAIR2) expression and cellular immune function, prognosis in patients with non-small cell lung cancer.Methods:From April 2016 to April 2017, 90 patients with non-small cell lung cancer who were treated in Shangqiu first people’s Hospital were taken as the lung cancer group, and they were grouped into the survival group and the death group according to whether the patients died within 5 years. Another 84 patients with benign pulmonary mass were selected as the control group. The levels of CD4+[ (28.26±5.14) % vs (47.02±6.73) %], CD8+ [ (23.76±5.84) % vs (30.12±6.03) %] and CD4+/CD8+ [ (1.17±0.30) % vs (1.56±0.50) %] in peripheral blood immune cells were detected by flow cytometry; the serum LAIR2 level was detected by enzyme-linked immunosorbent assay (ELISA) , and the average serum LAIR2 level of patients with non-small cell lung cancer was applied as the boundary, and they were grouped into a low LAIR2 expression group and a LAIR2 high expression group; Pearson correlation was applied to analyze the correlation between serum LAIR2 level and immune cell level in patients with non-small cell lung cancer; Kaplan-Meier curve was applied to analyze the relationship between serum LAIR2 level and 5-year survival rate of patients with non-small cell lung cancer; and multivariate COX regression analysis was applied to analyze the factors affecting 5-year mortality in patients with non-small cell lung cancer.Results:The level of serum LAIR2 [ (69.55±13.12) ng/ml vs. (20.64±7.13) ng/ml] in the lung cancer group was significantly higher than that in the control group, and the levels of CD4 +, CD8 + and CD4+/CD8+ were significantly lower than those in the control group ( P<0.05) . The serum LAIR2 level in patients with TNM stage III+IV (77.32±13.09) ng/ml, poorly differentiated tissue (78.14±13.26) ng/ml, and lymph node metastasis (79.02±13.81) ng/ml was significantly higher than that in patients with TNM stage I+II (64.37±12.89) ng/ml, medium/well differentiated tissue (64.32±12.73) ng/ml, and no lymph node metastasis (62.92±12.85) ng/ml ( P<0.05) . The levels of CD4 +, CD8 + and CD4 +/CD8 + in the LAIR2 high expression group were significantly lower than those in the LAIR2 low expression group ( P<0.05) . Serum LAIR2 level in patients with non-small cell lung cancer was negatively correlated with CD4+, CD8+ and CD4+/CD8+ levels ( r=-0.510, -0.496, -0.494, P<0.05) . The 5-year survival rate of patients with high LAIR2 expression was lower than that of patients with low LAIR2 expression ( r=6.375, P<0.05) . LAIR2 was an independent risk factor for 5-year death in patients with non-small cell lung cancer ( P<0.05) . Conclusion:LAIR2 is highly expressed in serum of patients with non-small cell lung cancer, and its expression level is closely related to cellular immune function and prognosis.

Objective: To analyze associated factors of HIV infection among college students who are young men and have sex with men (YMSM) in Tianjin, providing reference for HIV prevention and control among YMSM college students. Methods: During Aug. 1st, 2018 to Dec. 31st, 2018, SHENLAN recruited college students who were YMSM aged 18-24 years from gay baths, gay bars, QQ, WeChat and gay dating app BLUED. HIV infection status and associated factors (general demographic characteristics, unsafe sexual behaviors, addictive substance using, basic knowledge of HIV) was collected and analyzed. Results: A total of 470 college students, including 21 HIV infected (4.47%), were enrolled in this study. Univariate Logistic regression analyses indicated that age, age at first sex behavior, HIV related knowledge, tobacco use, recreational drug usage, syphilis infection was associated with HIV infection among YMSM students (P<0.05). Multivariate analysis found age of first sex (OR=21.20，95%CI=3.09-145.43), recreational drug use (OR=5.07，95%CI=1.77-14.48), lack of HIV related knowledge (OR=3.38，95%CI=1.33-8.63)were associated with HIV infection (P<0.05). Conclusion College students who are YMSM in Tianjin have a high rate of HIV infection, who deserves further attention. Targeted campus HIV/AIDS prevention program should be developed combined with specific characteristics of this population.

Objective To evaluate the effect of Eucommia on hyperlipidemia and related indexes in rats, and provide animal data useful for the clinical experimental studies on hyperlipidemia.Methods Seventy-two healthy male SD rats were used in this study.One group of 12 rats fed with normal diet was chosen as normal control group, and other 60 rats were fed with high fat diet for two weeks to generate rat models of hyperlipidemia.48 of the hyperlipidemic model rats were taken and divided randomly into 4 groups, including model group, high dose Eucommia, moderate dose Eucommia, and low dose Eucommia groups.The last three groups were gavaged different dose of Eucommia, respectively.Druing this period, the other groups except the normal control group were fed with high fat diet continuously.The levels of serum TC, TG, LDL-C, and HDL-C of rats were measured on day 30 and 45.Results The serum levels of TC and LDL-C of the rats in the model group were obviously higher than those in the normal control group.The rat models of hyperlipidemia were established successfully.The three dose groups had a tendency of lowing blood lipid after 30 days.At 45 days, the levels of serum TC and LDL-C in the low and high dose groups were lower than those in the model group (P<0.01, P<0.05), (P<0.01, P<0.01).TG in the high, moderate and low dose groups were lower than that in the model group (P<0.01, P<0.01, P<0.01), but the level of the serum HDL-C was not significantly lower than that in the model group (P>0.05, P>0.05, P>0.05).Conclusions Eucommia in a dose of 0.43 g/kg, 0.86 g/kg and 1.71 g/kg administered for 30 days have a tendency to reduce the level of serum TC, TG, and LDL-C.When Eucommia is administered in a dose of 0.43 g/kg, 1.71g/kg and 3.42 g/kg for 45 days, it shows an adjuvant hypolipidemic effect.

Objective To observe the host response and the expression of interleukin-4 (IL-4) in different cross-linked hyaluronic acid composite gels at different time points after the implantation in vivo, and to explore the significance of biocompatibility and macrophage polarization in post-implantation inflammatory response and tissue remodeling. Methods New Zealand white rabbits were respectively injected with crosslinked hyaluronic acid-crosslinked hydroxypropyl methylcellulose gel (sample 1), crosslinked hyaluronic acid-hydroxypropyl methylcellulose gel (sample 2) and commercially available modified sodium hyaluronate gel (control) in subcutaneous tissue at both sides of the spine. Then the rabbits were dissected at 1, 4 and 12 weeks after the implantation. The tissues were fixed with 10％formaldehyde solution, embedded in paraffin and sliced. Hematoxylin-eosin (HE) staining was performed to observe the degree of inflammation and fibrosis. Masson staining was performed to observe the formation of collagen fibers. Immunohistochemical staining was performed to observe the expression of IL-4. Results The results of HE staining showed that the inflammatory reaction in the sample 1 and sample 2 groups was significantly higher than that in the control group 1 and 4 weeks after the implantation. The inflammatory cells aggregated, and the wall of capsule and microcapsule was thick. The sample 1 group was more obvious, and the result was mild stimulation. For all the groups, the results were all non-irritating at 12 weeks after the implantation. The results of Masson staining showed that the collagen fibers in the sample 1 and sample 2 groups were increased compared with the control group, mainly distributed around the implantation site, and a small amount among the gels after 1 and 4 weeks. After 12 weeks, the collagen fibers were further increased, especially among the gels, which were consistent with the control group. The results of immunohistochemical staining showed that, at the same time point, the expression of IL-4 in sample 1 and sample 2 groups was higher than that in the control group, and the expression of IL-4 increased gradually with time. The expression of IL-4 in the control and sample 1 group at 12 weeks after the implantation was higher than that at 1 and 4 weeks respectively, and the differences were statistically significant (all P<0.05). In the sample 1 group, the expression of IL-4 at 12 weeks after the implantation was higher than that at 1 week, and the difference was statistically significant (P<0.05). The expression of IL-4 in the sample 1 group was significantly higher than that in the control group at 4 weeks after the implantation, and the difference was statistically significant (P<0.05). Conclusions The two different cross-linked sodium hyaluronate composite gels have good biocompatibility. The formation of collagen fiber and the expression of IL-4 can gradually increased within 12 weeks after the subcutaneous implantation, which is beneficial to the tissue remodeling.

Objective To understand the research status and development trend in the field of molecular and cell biology of thyroid cancer.Methods Relevant literature published in the field of molecular and cell biology of thyroid cancer from January 1,2013 to December 31,2022 was obtained in the web of science core collection(WoSCC)according to the search conditions,and bibliometric and visual analysis were performed using the bibliometric software VOSviewer and Excel.Results A total of 1 627 literatures were included.Among them,113 papers were published in 2013,and 214 were published in 2022.The annual number of publications was on the rise.There were 9 274 authors in total,of whom 6 published no less than 10 literatures.There were a total of 2 042 institutions,of which the top 10 institutions were mostly Chinese universities.There were 68 countries in total,and the largest number of publications was China,followed by the United States.There were 513 journals in total,and the top 10 journals with the largest number of literatures were mainly in the field of oncology,followed by the field of endocrinology and metabolism.A total of 62 563 references from 5 887 journals were cited.The most co-cited journal was Journal of Biological Chemistry(1 608 times),and the most co-cited references was Molecular Pathogenesis and Mechanisms of Thyroid Cancer(89 times).Conclusion The field of molecular and cell biology of thyroid cancer is currently developing steadily.Ferroptosis,glycosylation,telomerase reverse transcriptase and oxidative stress are the research frontiers in this field.

Background::Hepatic ischemia-reperfusion injury (HIRI) remains a common complication during liver transplantation (LT) in patients. As a key downstream effector of the Hippo pathway, Yes-associated protein (YAP) has been reported to be involved in various physiological and pathological processes. However, it remains elusive whether and how YAP may control autophagy activation during ischemia-reperfusion.Methods::Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy activation. Both an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of regulation. Results::Autophagy was activated in the post-perfusion liver grafts during LT in patients, and the expression of YAP positively correlated with the autophagic level of hepatocytes. Liver-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI ( P <0.05). YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models ( P <0.05). Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with 3-methyladenine. In addition, inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species ( P <0.05). Moreover, the regulation of autophagy by YAP during HIRI was mediated by AP1 (c-Jun) N-terminal kinase (JNK) signaling through binding to the transcriptional enhanced associate domain (TEAD). Conclusions::YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of hepatocytes. Targeting Hippo (YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.

Objective:To investigate the safety and the efficacy of percutaneous and surgical approach in femoro-femoral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) cannulation.Methods:All consecutive patients implanted with femoro-femoral VA-ECMO between January 2018 and December 2020 in Beijing Anzhen Hospital, Capital Medical University. Propensity score matching was used to compare outcomes of percutaneous and surgical groups while controlling for confounders.Results:Among the 276 patients who received femoro-femoral VA-ECMO (62 surgical and 214 percutaneous), propensity-score matching selected 52 pairs of patients with similar characteristics with mean age of(59.6±13.0)years old, in which 26 patients were female. There were a lower ECMO cannulation-associated complication (28.8% vs. 48.1%, P=0.044) and a lower hospital mortality (42.3% vs. 67.3%, P=0.010) in the percutaneous group. The circuit blood flow after ECMO initiation was similar in both groups[(3.3±0.8)L·min -1·kg -1 in percutaneous group vs. (3.2±0.7)L·min -1·kg -1 in surgical group, P=0.738]. The serum lactate was declined in both group after ECMO initiation[(5.4±5.8)mmol/L vs. (9.2±6.9)mmol/L, P<0.001 in percutaneous group; (6.3±6.2)mmol/L vs. (10.5±7.0)mmol/L, P=0.003 in surgical group]. Conclusion:Percutaneous approach is a safe and efficient technique in emoro-femoral VA-ECMO cannulation. Compared with surgical cannulation, percutaneous approach is associated with lower ECMO cannulation-associated complication and lower hospital mortality.

ObjectiveThe bioinformatics method was used to screen ferroptosis differential genes （FRGs） closely related to ulcerative colitis （UC）， and animal experiments were conducted to verify whether the mechanism of Xiezhuo Jiedu recipe in treating UC is related to the regulation of ferroptosis. MethodThe differentially expressed genes （DEGs） of colonic mucosa tissue of UC patients were obtained from the GEO database， and the intersection of the genes with ferroptosis genes was used to obtain FRGs. The core FRGs were obtained by cluster analysis， minimum absolute contraction and selection operator （LASSO） regression， and receiver operating characteristic curve （ROC） curve analysis. In animal experiments， the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate （DSS）. Xiezhuo Jiedu recipe and mesalazine were given by gavage for seven days， and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of E3 ubiquitin ligase （FBXW7）， zinc finger protein （ZFP36）， solute carrier family 7 member 11 （SLC7A11）， and Toll-like receptor 4 （TLR4） in colon tissue. The protein expression levels of FBXW7， ZFP36， SLC7A11， and TLR4 in colon tissue were detected by Western blot. ResultDataset GSE87466 was screened from the GEO database， and its intersections with the ferroptosis gene were analyzed to obtain 21 FRGs. After cluster analysis， LASSO regression， and ROC analysis， core FRGs （FBXW7， ZFP36， SLC7A11， and TLR4） were obtained. Immunoinfiltration analysis showed significant differences in the expression of initial B cells， M1 macrophages， plasma cells， and M2 macrophages in the colonic mucosa tissue of UC mice， and there was a significant correlation between core FRGs and these immune cells. Further animal experiments showed that the colonic mucosa tissue of mice in the model group was disorganized and infiltrated by a large number of inflammatory cells. The inflammation of the colonic mucosa tissue of mice in each group was relieved to varying degrees after treatment with Xiezhuo Jiedu recipe and mesalazine， while the colonic mucosa tissue of mice in the high-dose group of Xiezhuo Jiedu recipe showed almost no inflammatory changes. Compared with the normal group， the protein and mRNA expressions of FBXW7， ZFP36， SLC7A11， and TLR4 in the model group were significantly increased， and the expression of core FRGs in colonic mucosa tissue of mice in all groups was significantly down-regulated after treatment with Xiezhuo Jiedu recipe and mesalazine. ConclusionFBXW7， ZFP36， SLC7A11， and TLR4 are ferroptosis genes closely related to the pathogenesis of UC， and Xiezhuo Jiedu recipe can significantly alleviate colonic mucosa inflammation in mice by down-regulating core ferroptosis genes.