Tumor necrosis factor-α(TNF-α)is involved in the regulation of multiple biological processes such as the proliferation,invasion,migration,and chemotherapy resistance of hepatocellular carcinoma(HCC)cells through TNF receptor-mediated signaling pathways.At the same time,TNF-α also plays a role in inducing the apoptosis of HCC cells.Some TNF-α inhibitors have been shown to inhibit the progression of HCC and prolong survival time.At present,the potential mechanism of action of TNF-α in HCC remains unclear,and exploration of the interaction between TNF-α and HCC can help to determine the potential therapeutic targets for HCC.This article summarizes the latest research advances in the mechanism of action of TNF-α in HCC and introduces the possibility of targeting TNF-α as a treatment method for HCC,in order to provide a theoretical basis for the prevention and treatment of liver cancer and drug research and development.

Objective:To investigate the effect and mechanism of isorhynchophylline (IRN) on angiotensin Ⅱ(Ang Ⅱ)-induced cardiac hypertrophy.Methods:H9c2 cells were co-cultured with Ang Ⅱ and different concentrations of IRN (0, 5, 10, 25, 50 μmol/L). The cell surface area and mRNA levels of cardiac hypertrophy markers atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) were detected to elucidate the effect of IRN on myocardial hypertrophy and the most effective concentration. H9c2 cells were co-cultured with Ang Ⅱ and IRN (25 μmol/L) at different times (0, 6, 12, 24 h) to elucidate the most effective time of inhibition. The phosphorylation levels of the signaling pathway were detected, and the effects of IRN and Akt inhibitor MK2206 on the phosphorylation levels of the signaling pathway were further explored to elucidate the underlying mechanisms.Results:Compared with the control group, the surface area of H9c2 cells, and the mRNA expression of myocardial hypertrophy markers ANP, BNP and β-MHC were significantly increased (all P<0.05). Pretreated with different concentrations of IRN (5, 10, 25, 50 μmol/L) could inhibit the increase in cell surface area induced by AngⅡ (all P<0.05), especially at the concentration of 25 μmol/ L ( P<0.01). IRN could time-dependently inhibit AngⅡ-induced activation of ANP, BNP, β-MHC mRNA (all P<0.05). AngⅡ caused increased phosphorylation levels of Akt, GSK3β, mTOR and FOXO3a. IRN could block AngⅡ-induced phosphorylation of the Akt signaling pathway. Conclusion:IRN attenuates AngⅡ-induced cardiomyocyte hypertrophy by inhibiting the Akt signaling pathway.

Purpose To investigate the expression and po-tential clinical value of heat shock protein 90α(Hsp90α)in co-lon adenocarcinoma.Methods The expression level of Hsp90αin colon adenocarcinoma and its relationship with clinicopatho-logical features,prognosis and immune cell infiltration were ana-lyzed by bioinformatics and immunohistochemistry.The prolifer-ation ability of colon cancer cells before and after Hsp90AA1 knockout was detected by CCK-8 cell proliferation assay and plate cloning assay.Results The bioinformatics tools showed that Hsp90AA1 was abnormally higher in colon cancer tissues than adjacent tissues,and the higher the expression level,the worse the prognosis of patients.The expression of Hsp90AA1 was positively correlated with the infiltration levels of CD4+T cells(Th2),CD8+T cells,myeloid inhibitory cells,Tregs cells,neutrophils,macrophages,M1 macrophages and M2 macropha-ges.Immunohistochemical results showed that the expression of Hsp90α in colon cancer tissues was significantly higher than in its adjacent tissues.The expression of Hsp90α was related to age(P＜0.05),not related to gender,tumor size,location,clini-cal classification,differentiation degree,tumor node metastasis,lympho-vascular invasion,perineural invasion(P＞0.05).The high expression of Hsp90α was an independent risk factor for the prognosis of colon cancer patients.The results of cell experi-ments showed that Hsp90AA1 knockout inhibited the growth and proliferation of colon cancer cells.Conclusion Hsp90α is highly expressed in colon adenocarcinoma,which may be a po-tential molecular marker for poor prognosis of colon adenocarci-noma.

BACKGROUND: Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent. This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules. METHODS: Multiple databases with relevant studies were searched with an end date of October 31, 2021, and a website including a series of Coronavirus disease 2019 studies was examined for studies before March 31, 2022. Randomized controlled trials (RCTs) that compared different heterologous and homologous regimens among adults that reported immunogenicity and safety outcomes were reviewed. Primary outcomes included neutralizing antibodies against the original strain and serious adverse events (SAEs). A network meta-analysis (NMA) was conducted using a random-effects model. RESULTS: In all, 11 RCTs were included in the systematic review, and nine were ultimately included in the NMA. Among participants who received two doses of CoronaVac, another dose of mRNA or a non-replicating viral vector vaccine resulted in a significantly higher level of neutralizing antibody than a third CoronaVac 600 sino unit (SU); a dose of BNT162b2 induced the highest geometric mean ratio (GMR) of 15.24, 95% confidence interval [CI]: 9.53-24.39. Following one dose of BNT162b2 vaccination, a dose of mRNA-1273 generated a significantly higher level of neutralizing antibody than BNT162b2 alone (GMR = 1.32; 95% CI: 1.06-1.64), NVX-CoV2373 (GMR = 1.60; 95% CI: 1.16-2.21), or ChAdOx1 (GMR = 1.80; 95% CI: 1.25-2.59). Following one dose of ChAdOx1, a dose of mRNA-1273 was also more effective for improving antibody levels than ChAdOx1 (GMR = 11.09; 95% CI: 8.36-14.71) or NVX-CoV2373 (GMR = 2.87; 95% CI: 1.08-3.91). No significant difference in the risk for SAEs was found in any comparisons. CONCLUSIONS: Relative to vaccination with two doses of CoronaVac, a dose of BNT162b2 as a booster substantially enhances immunogenicity reactions and has a relatively acceptable risk for SAEs relative to other vaccines. For primary vaccination, schedules including mRNA vaccines induce a greater immune response. However, the comparatively higher risk for local and systemic adverse events introduced by mRNA vaccines should be noted. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42021278149.
Adult ; Humans ; BNT162 Vaccine ; 2019-nCoV Vaccine mRNA-1273 ; Network Meta-Analysis ; Immunization Schedule ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; Viral Vaccines ; mRNA Vaccines ; Antibodies, Neutralizing ; Antibodies, Viral

Objective:To explore the relationship between thyroid parenchymal echogenicity abnormalities and thyroid function evolution in health examination population.Methods:It was a cohort study. According to the inclusion and exclusion criteria, participants were selected from individuals who underwent thyroid color ultrasound and thyroid function tests at the Health Management Center of Tianjin Medical University General Hospital from January to December 2017. Data including age, gender, smoking history, alcohol consumption history, personal medical history, and thyroid function re-examination information were collected. Follow-up was conducted until the occurrence of thyroid function abnormalities or until the end of the follow-up period. The cumulative incidence rate and incidence density of thyroid function abnormalities were evaluated. Cox regression analysis was used to analyze the relationship between thyroid parenchymal echogenicity abnormalities and thyroid function evolution.Results:A total of 6 754 participants were included in this study, with an average age of (45.80±12.12) years, and females accounted for 42.7%. The mean follow-up time was 1.82 years, with a cumulative follow-up duration of 12 263 person-years. During the follow-up period, 154 new cases of thyroid function abnormalities occurred, with a cumulative incidence rate of 2.28% (95% CI: 1.94%-2.66%) and an incidence density of 12.56/1 000 person-years (95% CI: 10.66/1 000-14.69/1 000 person-years). The multivariate adjusted Cox regression analysis showed that individuals with thyroid parenchymal echogenicity abnormalities had a significantly increased risk of developing isolated thyroid stimulating hormone abnormalities and thyroid function abnormalities, with HR(95% CI) of 3.09 (2.02-4.73) and 2.92(1.96-4.33), respectively, both P<0.001. Stratified analysis showed that, except for body mass index <18.5 kg/m 2, current smoking, and current alcohol consumption, all other stratified factors showed a significant increase in the risk of thyroid function abnormalities in individuals with thyroid parenchymal echogenicity abnormalities. Conclusion:Thyroid parenchymal echogenicity abnormalities are important risk factors for the evolution of thyroid function abnormalities. Continuous monitoring of thyroid function should be given due attention.

Objective:To analyse the current status of parturients' readiness for discharge, family functioning and psychological consistency, and to explore the relationship readiness for discharge, family functioning and psychological consistency.Methods:This was a cross-sectional study. Using the convenient sampling method, a total of 429 parturient women admitted to Obstetrics Department in two ClassⅢ Grade A hospitals in Yinchuan City from March to July 2022 were selected as the research objects. General Information Questionnaire, Family Assessment Device (FAD) , Readiness for Hospital Discharge Study-New Mother Form (RHDS-NMF) and Sense of Coherence-13 (SOC-13) were used to investigate the patients. A total of 429 questionnaires were sent out in this study, and 418 questionnaires were effectively collected, with an effective recovery rate of 97.44% (418/429) .Results:The total score of RHDS-NMF in 418 parturient women was (131.18±24.96) , the total score of FAD was (127.76±15.57) , and the total score of SOC-13 was (54.59±7.22) . The discharge readiness of parturient women was negatively correlated with family function ( r=-0.332, P<0.01) , while discharge readiness was positively correlated with psychological consistency ( r=0.253, P<0.01) . The mediation effect analysis results showed that psychological consistency played a partial mediating role between family function and discharge readiness in parturient women, with a mediation effect value of -1.105 ( P<0.05) , accounting for 27.1% of the total effect. Conclusions:Psychological consistency plays a partial mediating role between family function and discharge readiness in parturient women. Medical staff should pay attention to the evaluation and intervention of parturients' psychological consistency, enhance their level of psychological consistency and improve readiness for discharge.

ObjectiveTo determine the therapeutic effect of Gegentang granules on a disease-syndrome mouse model combining human coronavirus 229E （hCoV-229E） pneumonia with Hanshi Yidu Xifei syndrome in vivo. MethodMice were randomly divided into normal group， infection group， cold-dampness group， model group， chloroquine phosphate group （0.18 g·kg^-1）， interferon-α2b （IFN-α2b） group （1.83×10⁶ U·kg^-1）， Gegentang granules high-dose and low-dose groups （6.6， 3.3 g·kg^-1） with 10 mice in each group. Cold-dampness environment and hCoV-229E infection were used for modeling， and the general status and lung index of mice in each group were observed. The viral load in lung tissue was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， the pathological changes in lung tissue were evaluated by hematoxylin-eosin （HE） staining， the levels of serum gastrointestinal hormones and inflammatory factors in lung tissue were detected by enzyme-linked immunosorbent assay （ELISA）， and the percentage of peripheral blood lymphocytes was detected by flow cytometry. ResultComparing with model group， Gegentang granules could significantly alleviate the physical signs of Hanshi Yidu Xifei syndrome， including listlessness， weakness of limbs， sticky stool， etc. Comparing with model group， Gegentang granules high-dose group significantly reduced lung index， histopathological score of interstitial lung and bronchus， and the level of serum motilin （P<0.05， P<0.01）， two doses of Gegentang granules could significantly increase the level of serum gastrin （P<0.05， P<0.01）， the percentage of CD4⁺， CD8⁺ T lymphocytes in peripheral blood （P<0.05， P<0.01）， and the level of tumor necrosis factor-α （TNF-α） in lung tissue was significantly decreased （P<0.01）， and the level of interleukin-6 （IL-6） showed decreasing tendency. ConclusionGegentang granules has therapeutic effect on model mice. It can improve the appearance and behavior characterization， regulate the level of gastrointestinal hormones， decrease lung index and histopathological score， and possibly play an immunomodulatory role by inhibiting the expression of inflammatory cytokines in lung tissue and restoring the percentage of peripheral blood lymphocytes.

Objective:To investigate the inhibitory effect and mechanism of heme oxygenase-1 (HO-1) on the inflammatory response of macrophages.Methods:Mouse macrophage strain RAW264.7 was cultured in vitro, and the cells in the logarithmic growth phase were used for the experiment. The RAW264.7 cells were divided into four groups. In blank control group, the cells were continuously incubated and received no treatment (cultured at 37 ℃, 95% air, 5% CO 2). In lipopolysaccharide (LPS) model group, 1 mg/L LPS was added to the medium to prepare LPS challenge model. In HO-1 inducer group, the cells were incubated with 30 μmol/L HO-1 inducer hemin for 1 hour, and then 1 mg/L LPS was added for incubation. In HO-1 inhibition group, the cells were incubated with 5 μmol/L HO-1 specific antagonist Zinc protoporphyrin Ⅸ (ZnPPⅨ) for 0.5 hour, and then 1 mg/L LPS was added for incubation. After 48 hours of incubation with LPS, the supernatant of each group was taken, and the protein expressions of HO-1, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), thioredoxin interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3) and mitochondrial autophagy marker microtubule-associated protein 1 light chain 3B (LC-3B) were detected by Western blotting. The expression of reactive oxygen species (ROS) was detected by immunofluorescence staining. Results:Compared with the blank control group, the cells in the LPS model group had a certain stress response, and autophagy occurred in mitochondria, but the expression of some inflammatory factors was restricted, which was related to the impairment of cell function. The protein expressions of HO-1, IL-1β, LC-3B, ROS were significantly increased, the protein expressions of TNF-α, TXNIP, and NLRP3 were decreased significantly, indicating that the cells were seriously injured after LPS challenge, and the model was successfully established. Compared with the LPS model group, HO-1 protein expression in the HO-1 inducer group was significantly increased (HO-1/GAPDH: 0.31±0.03 vs. 0.22±0.03, P < 0.05), the protein expressions of TNF-α, IL-1β, TXNIP, NLRP3, LC-3B and ROS were significantly inhibited [TNF-α protein (TNF-α/GAPDH): 0.08±0.01 vs. 0.45±0.05, IL-1β protein (IL-1β/GAPDH): 0.50±0.01 vs. 0.82±0.03, TXNIP protein (TXNIP/GAPDH): 0.21±0.02 vs. 0.28±0.02, NLRP3 protein (NLRP3/GAPDH): 0.11±0.01 vs. 0.17±0.02, LC-3B protein (LC-3B/GAPDH): 0.67±0.04 vs. 0.92±0.12, ROS (fluorescence intensity): 80.9±12.5 vs. 94.1±19.5, all P < 0.05], indicating that HO-1 could inhibit inflammatory response and oxidative stress, and reduce mitochondrial autophagy. Antagonizing HO-1 could increase inflammatory response, oxidative stress and mitochondrial autophagy, the inhibitory degree of TNF-α and IL-1β expression was significantly reduced as compared with the HO-1 inducer group [TNF-α protein (TNF-α/GAPDH): 0.26±0.02 vs. 0.08±0.01, IL-1β protein (IL-1β/GAPDH): 0.76±0.01 vs. 0.50±0.01, both P < 0.05], the protein expressions of TXNIP, NLRP3, LC-3B and ROS were significantly increased as compared with the LPS model group [TXNIP protein (TXNIP/GAPDH): 0.43±0.02 vs. 0.28±0.02, NLRP3 protein (NLRP3/GAPDH): 0.24±0.02 vs. 0.17±0.02, LC-3B protein (LC-3B/GAPDH): 1.12±0.07 vs. 0.92±0.12, ROS (fluorescence intensity): 112.0±17.0 vs. 94.1±19.5, all P < 0.05]. Conclusion:HO-1 can reduce the inflammatory response by inhibiting the activation of TXNIP/NLRP3 inflammasome and reducing the release of inflammatory mediators.

ObjectiveTo investigate the protective effect of fecal microbiota transplantation (FMT) on mice with acute-on-chronic liver failure (ACLF) and its effect on intestinal flora. MethodsA total of 40 mice were randomly divided into control group (CON group), model group (MOD group), FMT group (feces of the mice in the CON group were used as fecal microbiota donor), and FMT model group (ANFMT group, with feces of the mice in the MOD group as fecal microbiota donor), with 10 mice in each group. All mice were observed in terms of body weight, death, liver histopathology, and changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and intestinal flora. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the SNK-q test was used for further comparison between two groups. ResultsCompared with the CON group, the MOD group had a significant reduction in body weight and significant increases in AST and ALT (all P＜0.05), as well as large patchy necrosis of hepatocytes, significant increases in Verrucomicrobia, Akkermansia, and Erysipelatoclostridium, and significant reductions in Dubosiella and Duncaniella (all P＜0.05). Compared with the CON group, the ANFMT group had a significant increase in AST (P＜0.05), hepatocyte swelling and mild ballooning degeneration, significant increases in Unclassified and Faecalibaculum, and significant reductions in Patescibacteria, Deferribacteres, Muribaculum, Candidatus_Saccharimonas, Rikenella, Odoribacter, Mucispirillum, and Lachnospiraceae_unclassified (all P＜0.05). Compared with the MOD group, the FMT group had significant reductions in AST and ALT (both P＜0.05), mild hepatocellular necrosis and marked ballooning degeneration, significant increases in Paramuribaculum and Bilophila, and significant reductions in Firmicutes, Rikenella, and Absiella (all P＜0.05). ConclusionIntestinal flora disturbance is observed in ACLF mice, and dysbacteriosis may lead to liver injury. FMT can alleviate liver inflammation in ACLF mice and thus exert a protective effect.

Objective:To analyze the blood glucose screening condition for individuals receiving physical examinations. Specifically, to examine the rates of abnormal postprandial glucose at different levels of fasting blood glucose and the characteristics of people who had normal fasting blood glucose with high postprandial glucose.Methods:Participants were individuals who received physical examinations at the Health Management Centre, Tianjin Medical University General Hospital, from January 2016 to December 2016. Data collection included general information, physical examination, and laboratory tests including fasting blood glucose, HbA1c, postprandial glucose, blood fat, and blood uric acid. The blood glucose indicators for the study population were analyzed. Among participants without diabetes, the rate of abnormal postprandial glucose at different fasting blood glucose levels or with a HbA1c screening were compared. For participants with complete information, chi-square tests and multivariate logistic regressions were used to analyze the characteristics of individuals who had normal fasting blood glucose with high postprandial glucose.Results:A total of 45 447 participants were included, with 23 001 males (50.61%) and 22 446 females (49.39%). For blood glucose, the most frequently completed indicator was fasting blood glucose (97.04%), then HbA1c (56.17%) followed by postprandial glucose (17.51%). There were 7 351 participants without diabetes who had all three glucose indicators. As fasting blood glucose increased, the abnormal rate of postprandial glucose increased gradually. When fasting blood glucose was lower than 5.6 mmol/L, the rate of abnormal postprandial glucose was 11.59%. When fasting blood glucose was between 5.6 mmol/L and 6.1 mmol/L, the rate was 33.9%. When fasting blood glucose was higher than 6.1 mmol/L, the rate was 68.73%. When the cutoff for fasting blood glucose was 5.6 mmol/L, the rate of abnormal postprandial glucose decreased compared with a cutoff of 6.1 mmol/L (11.59% vs. 14.32%, respectively). Combined with HbA1c screening, the rate of postprandial glucose abnormalities were both reduced (8.83% vs.11.59% for 5.6 mmol/L; 10.08% vs. 14.32% for 6.1 mmol/L). A total of 5 872 individuals had complete information and were included in the analysis. Participants who were men, >45 years old, and were overweight or obese had higher risk for abnormal postprandial glucose [ OR(95% CI): 2.85(2.33-3.48), 2.15(1.76-2.62), 1.82(1.45-2.27), and 2.64(2.04-3.42), respectively, P<0.05]. Hypertension, hyperlipidemia and hyperuricemia were also risk factors [ OR(95% CI): 1.80(1.51-2.15) and 1.52(1.27-1.82), respectively, P<0.05] Conclusions:The completion rate was highest for fasting blood glucose and lowest for postprandial glucose among the study population. The rate of abnormal postprandial glucose was high when fasting blood glucose was normal. Screening combined with HbA1c decreased the rate of postprandial glucose abnormalities. Postprandial glucose testing should be recommended for those who are male, older, overweight or obese, and have other risk factors including hypertension, hyperlipidemia, and hyperuricemia.