OBJECTIVE To compare the anti-hepatitis mechanisms of Abrus pulchellus subsp. cantoniensis （Hance） Verdc. （AC） and Abrus pulchellus subsp. mollis（Hance） Verdc. （AM）. METHODS SD rats were randomly divided into blank group， AC- treated group， and AM-treated group， with each group consisting of 10 rats. The rats’ orbital venous blood was collected at 5， 15， 30 minutes， and 1， 1.5， 2， 4， 6， 8， 12 hours after gavage administration of 24 g/kg of the corresponding drug （calculated by crude drug） or water， respectively. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry technology was utilized to identify the prototype components present in the serum. The network pharmacology method was adopted to predict the anti-hepatitis active components， key targets， and signaling pathways of AC and AM. Additionally， molecular docking technology was utilized to verify the binding activity of the core active components with key targets. RESULTS A total of 35 prototype components migrating to the blood of AC and AM were identified in the serum of administered rats， among which 24 were common components. The active components in AC， such as acetylanguidine， physcion， soyasaponin A3 and soyasaponin Ⅰ， as well as those in AM， including vicenin 3， acetylanguidine，soyasaponin Ⅰ and schaftoside， all acted on key targets such as steroid receptor coactivator， phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit alpha， epidermal growth factor receptor （EGFR）， and protein kinase B1（Akt1）. These components modulated pathways in cancer， EGFR tyrosine kinase inhibitor resistance， and the phosphoinositide 3-kinase （PI3K） -Akt pathway， thereby exerting anti-hepatitis effects. Furthermore， the binding energies between these active components and their key targets were all less than －5 kJ/mol. CONCLUSIONS There are differences in the active components of AC and AM against hepatitis， but their mechanisms of action are similar. Both may exert their anti-hepatitis effects through pathways in cancer， EGFR tyrosine kinase inhibitor resistance， and the PI3K-Akt pathway.

Neutralizing antibodies have been designed to specifically target and bind to the receptor binding domain (RBD) of spike (S) protein to block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from attaching to angiotensin converting enzyme 2 (ACE2). This study reports a distinctive nanobody, designated as VHH21, that directly catalyzes the S-trimer into an irreversible transition state through postfusion conformational changes. Derived from camels immunized with multiple antigens, a set of nanobodies with high affinity for the S1 protein displays abilities to neutralize pseudovirion infections with a broad resistance to variants of concern of SARS-CoV-2, including SARS-CoV and BatRaTG13. Importantly, a super-resolution screening and analysis platform based on visual fluorescence probes was designed and applied to monitor single proteins and protein subunits. A spontaneously occurring dimeric form of VHH21 was obtained to rapidly destroy the S-trimer. Structural analysis via cryogenic electron microscopy revealed that VHH21 targets specific conserved epitopes on the S protein, distinct from the ACE2 binding site on the RBD, which destabilizes the fusion process. This research highlights the potential of VHH21 as an abzyme-like nanobody (nanoabzyme) possessing broad-spectrum binding capabilities and highly effective anti-viral properties and offers a promising strategy for combating coronavirus outbreaks.
Single-Domain Antibodies/immunology* ; Spike Glycoprotein, Coronavirus/metabolism* ; SARS-CoV-2/immunology* ; Animals ; Humans ; Antibodies, Neutralizing/immunology* ; Camelus ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Angiotensin-Converting Enzyme 2

Humans ; Urinary Bladder Neoplasms/pathology* ; Carcinoma, Transitional Cell/pathology* ; Genetic Markers ; Biomarkers, Tumor/genetics* ; Urothelium/pathology*

Pulmonary fibrosis is a respiratory system disorder characterized by damage to alveolar epithelial cells,pathological proliferation and transformation of fibroblasts,excessive deposition of extracellular matrix,leading to structural damage and loss of function in lung tissues,with a high mortality rate and limited effective treatment methods.This article was based on the TCM understanding of"lung connecting to large intestine",namely the theory of"lung and the large intestine being interior-exterior related",and set the modern medical understanding of"lung connecting to large intestine",namely the theory of"gut-lung axis"as the key.Combining the TCM pathogenesis of pulmonary fibrosis and the related mechanisms of"gut-lung axis"in pulmonary fibrosis,it preliminarily expounded the connotation of TCM regulating the"gut-lung axis"to treat pulmonary fibrosis,aiming to provide new ideas for clinical treatment of pulmonary fibrosis through the"gut-lung axis".

BACKGROUND: Cholecystectomy is a standard surgery for patients suffering from gallbladder diseases, while the causal effects of cholecystectomy on colorectal cancer (CRC) and other complications are still unknown. METHODS: We obtained genetic variants associated with cholecystectomy at a genome-wide significant level ( P value <5 × 10 -8 ) as instrumental variables (IVs) and performed Mendelian randomization (MR) to identify the complications of cholecystectomy. Furthermore, the cholelithiasis was also treated as the exposure to compare its causal effects to those of cholecystectomy, and multivariable MR analysis was carried out to judge whether the effect of cholecystectomy was independent of cholelithiasis. The study was reported based on Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization guidelines. RESULTS: The selected IVs explained 1.76% variance of cholecystectomy. Our MR analysis suggested that cholecystectomy cannot elevate the risk of CRC (odds ratio [OR] =1.543, 95% confidence interval [CI]: 0.607-3.924). Also, it was not significant in either colon or rectum cancer. Intriguingly, cholecystectomy might decrease the risk of Crohn's disease (OR = 0.078, 95% CI: 0.016-0.368) and coronary heart disease (OR = 0.352, 95% CI: 0.164-0.756). However, it might increase the risk of irritable bowel syndrome (IBS) (OR = 7.573, 95% CI: 1.096-52.318). Cholelithiasis could increase the risk of CRC in the largest population (OR = 1.041, 95% CI: 1.010-1.073). The multivariable MR analysis suggested that genetic liability to cholelithiasis could increase the risk of CRC in the largest population (OR = 1.061, 95% CI: 1.002-1.125) after adjustment of cholecystectomy. CONCLUSIONS The study indicated that cholecystectomy might not increase the risk of CRC, but such a conclusion needs further proving by clinical equivalence. Additionally, it might increase the risk of IBS, which should be paid attention to in clinical practice.
Humans ; Mendelian Randomization Analysis ; Irritable Bowel Syndrome ; Colorectal Neoplasms/genetics* ; Cholelithiasis/complications* ; Cholecystectomy/adverse effects* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

BACKGROUND: Vaccination has been shown effective in controlling the global coronavirus disease 2019 (COVID-19) pandemic and reducing severe cases. This study was to assess the flare and change in disease activity after COVID-19 vaccination in patients with stable rheumatoid arthritis (RA). METHODS: A prospective cohort of RA patients in remission or with low disease activity was divided into a vaccination group and a non-vaccination group based on their COVID-19 vaccination status. Each of them was examined every 3 to 6 months. In the vaccination group, disease activity was compared before and after vaccination. The rates of flare defined as disease activity scores based on 28-joint count (DAS28) >3.2 with ΔDAS28 ≥0.6 were compared between vaccination and non-vaccination groups. RESULTS: A total of 202 eligible RA patients were enrolled. Of these, 98 patients received no vaccine shot (non-vaccination group), and 104 patients received two doses of vaccine (vaccination group). The median time interval from pre-vaccination visit to the first immunization and from the second dose of vaccine to post-vaccination visit was 67 days and 83 days, respectively. The disease activity scores at pre-vaccination and post-vaccination visits in the vaccination group patients were similar. At enrollment, gender, RA disease course, seropositivity, and disease activity were comparable across the two groups. Flare was observed in five (4.8%) of the vaccination group patients and nine (9.2%) of the non-vaccination group patients at post-vaccination assessment ( P  = 0.221). In terms of safety, 29 (27.9%) patients experienced adverse events (AEs) after vaccination. No serious AEs occurred. CONCLUSIONS COVID-19 vaccinations had no significant effect on disease activity or risk of flare in RA patients in remission or with low disease activity. Patients with stable RA should be encouraged to receive the COVID-19 vaccination.
Humans ; Arthritis, Rheumatoid ; Cohort Studies ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; East Asian People ; Prospective Studies ; Vaccination/adverse effects*

Objective:To explore the feasibility and effectiveness of 3D printing aortic model for preoperative evaluation and surgical simulation, and to assist interventional treatment of coarctation of the aorta(CoA).Methods:From December 2017 to January 2019, 8 patients with congenital coarctation of the aorta who underwent percutaneous balloon dilatation and covered stent placement in Xijing Hospital of Air Force Military Medical University were analyzed retrospectively. Among them, 7 cases were male and 1 case was female. The age was(32.00±14.93) years old. Before operation, CT data of patients' heart and aorta were collected, reconstructed with Mimics software, and 3D printing technology was used to make the model of patients' aortic lesions. Before operation, the operation simulation was carried out to determine the best operation scheme and estimate the possible situation, and the relevant clinical data of patients during hospitalization and follow-up were collected.Results:One stent graft was successfully implanted into CoA through femoral artery in all 8 patients. The mean diameter of CoA increased from(3.70±2.94) mm before operation to(18.01±1.51) mm immediately after operation( P<0.05), and the mean systolic pressure difference decreased from(83.75±25.44) mmHg before operation to(14.63±8.09) mmHg after operation( P<0.05). The mean systolic blood pressure of the right upper extremity decreased from(204.13±22.31) mmHg before operation to(145.63±32.08) mmHg after operation( P<0.05), and there was no significant difference between the two groups. During the period of hospitalization and follow-up, no corresponding cardiovascular complications were found. Conclusion:The short-term effect of percutaneous balloon dilatation covered stent implantation on CoA in adolescents and adults is obvious. 3D printing model can reproduce the anatomical model of CoA site of patients individually, which is feasible and effective for the preoperative evaluation of CoA and the preparation of operation plan.

Objective: To investigate the characteristics and clinical significance of the immunomicroenvironment typing based on the expression of programmed death-ligand 1 (PD-L1) and the infiltration of CD8+ T cells in the stroma in patients with non-small cell lung cancer (NSCLC). Methods: Paraffin tissue specimens and relevant clinicopathological data of 74 NSCLC patients admitted to our hospital from January 2016 to July 2018 were collected.All patients received EGFR gene test, and none received radiotherapy, chemotherapy or targeted therapy. Immunohistochemistry was used to detect the expression of PD-L1 in tissues and the infiltration of CD8+T cells in interstitium, and the relationship between PD-L1, CD8+T cells, and the immune microenvironment typing based on both, and the pathological parameters and the survival of patients was analyzed. Results: PD-L1 expression in the primary tumor of NSCLC patients showed statistical differences in gender, pathological type, smoking history, EFGR gene mutation status ( P <0.05). The infiltration of CD8+ T lymphocytes in tumor microenvironment showed statistically significant differences in different TNM stage and lymph node metastasis ( P <0.05), PD-L1 expression was significantly correlated with EGFR mutation ( P =0.000), while CD8+T lymphocyte infiltration was not correlated with EGFR mutation ( P =0.605). The immunomicroenvironment of EGFR wild-type patients was mainly (CD8+ PD-L1+) (type I), and the mutants were mainly (CD8-PD-L1-) (type II) and (CD8+PD-L1-) (type IV). The distribution of immune microenvironmental typing in each group with different EGFR mutation, smoking history and pathological differentiation degree was significantly different ( P <0.05) and significantly correlated with EGFR mutation ( P <0.05). Follow-up showed that the patients with disease free survival, recurrence and metastasis and death were the most in type I, type II and type I, respectively. Conclusions: In this study, the distribution of tumor immunomicroenvironmental typing in NSCLC patients was mainly the highest in type I and the lowest in type Ⅲ, which was related to EGFR mutation, smoking history and pathological differentiation. Patients with EGFR mutations were mainly of type Ⅱand type Ⅳ, and were associated with low expression of PD-L1. ··

This study aimed to investigate whether β-elemene could improve the dysfunction of vascular endothelial cells induced by low shear force (LSS), and the proliferation and migration of vascular smooth muscle cells induced by oxidized low-density lipoprotein (ox-LDL). Parallel plate flow chambers and ox-LDL were used to establish vascular endothelial cells (ECs) dysfunction model and vascular smooth muscle cell (VSMCs) proliferation and migration model, respectively, and the effects of β-elemene on ECs dysfunction and VSMCs proliferation and migration were examined. The activity of ROS in ECs was measured by DHE and the activity of NO in ECs was tested by DAF-FM DA. The protein phosphorylation of Akt and ERK in ECs were detected by Western blot. The proliferation of VSMCs was measured by MTT. The migration of VSMCs was examined by cell scratch test and Transwell assay. The gene expression of MMP-2 and MMP-9 in VSMCs was measured by RT-qPCR. In ECs, β-elemene could significantly reduce the LSS-induced increase in ROS, significantly increase the LSS-induced decrease in NO, decrease the phosphorylation of ERK, and increase the phosphorylation of Akt. In VSMCs, β-elemene could significantly reduce the proliferation and migration of VSMCs induced by ox-LDL, and reduce the gene expression of MMP-2 and MMP-9. To conclude, β-elemene can improve the LSS-induced ECs dysfunction and ox-LDL-induced VSMCs proliferation and migration.

Objective To investigate the expressions of transforming growth factor β1 (TGF-β1) and brain natrium peptide (BNP) in patients with diastolic heart failure (DHF),and to explore the correlation between plasma levels of TGF-β1,BNP and TGF-β1/BNP with parameter of diastolic function,diastolic dysfunction and New York Heart Association (NYHA) classification of cardiac function.Methods Hospitalized patients with DHF from October 2016 to November 2017 in Beijing Chaoyang Hospital were selected as subjects.At the same time,the age-and gender-matched non-heart failure hospitalized patients were selected as the control.The diastolic function index (E/e') was measured using cardiac ultrasound spectral Doppler and tissue Doppler methods.The diastolic dysfunction classification was evaluated according to the American Society of Echocardiography guidelines.Cardiac function was evaluated with NYHA classification.The levels of plasma TGF-β1 and BNP were measured with method of enzyme linked immunosorbent assay (ELISA).The correlation between the indicators was analyzed and the receiver operating characteristic (ROC) curve was drawn.Results A total of 186 patients were enrolled,including 114 patients as DHF group [54 males and 60 females,mean age (70.75 ± 11.45) years old] and 72 cases as control group [41 males and 31 females,mean age (68.74 ± 10.86) years old].The levels of TGF-β1 [(77.68 ± 42.31) ng/L] and BNP [(1 153.84 ± 564.96) ng/L] in patients with DHF were significantly higher than those of the control group [(18.76 ± 13.70),(264.07 ± 179.43) ng/L,t =15.62,13.77,P ＜ 0.01].Pearson correlation analysis showed that level of plasma TGF-β1 had a significant liner correlation with index E/e' (r =0.582,P ＜ 0.01),level of plasma BNP had a low-degree liner correlation with index E/e' (r =0.261,P ＜ 0.01),and TGF-β1/BNP had no correlation with index E/e' (r =0.081,P ＞ 0.05).Spearman correlation analysis showed that the levels of TGF-β1 and BNP were significantly correlated with diastolic dysfunction grading (r =0.473,0.417,P ＜ 0.01),while TGF-β1/BNP had no correlation with diastolic dysfunction grading (r =0.062,P ＞ 0.05).Plasma TGF-β1 and BNP had low-degree correlation with NYHA classification of heart failure (r =0.309,0.326,P ＜ 0.01),TGF-β1/BNP had no correlation with NYHA classification of heart failure (r =0.011,P ＞ 0.05).Logistic analysis showed that both plasma TGF-β1 and BNP were independent predictors of DHF (OR =1.264,2.283,P ＜ 0.05 or ＜ 0.01).The area under ROC curve (AUC) of BNP for prediction of DHF was 0.937 ± 0.064,and TGF-β1 was 0.597 ± 0.042.AUC areas of BNP and TGF-β1 were significantly different (P ＜ 0.01).Conclusions The expressions of plasma TGF-β1 and BNP in patients with DHF are higher than those without DHF.The levels of plasma TGF-β1 and BNP are significantly correlated with index E/e',diastolic dysfunction grading and NYHA classification.Both elevated BNP and TGF-β1 levels are independent predictors of DHF.Both plasma BNP and TGF-β1 have auxiliary diagnostic value on DHF and the diagnostic value of plasma BNP is greater than plasma TGF-β1.