Objective To investigate the protective effect and mechanism of tanshinone ⅡA on D-galactosamine(D-GalN)-induced acute liver failure in rats.Methods SD rats were randomly di-vided into control group,model group(intraperitoneal injection of 1.1 g/kg D-GalN),low-dose group(intraperitoneal injection of 1.1 g/kg D-GalN+daily gavage of 25 mg/kg tanshinone ⅡA),and High-dose group(intraperitoneal injection of 1.1 g/kg D-GalN+daily gavage of 50 mg/kg tan-shinone ⅡA).Liver function indicators[aspartate aminotransferase(AST),alanine aminotransferase(ALT),and γ-glutamyltransferase(γ-GT)]were measured using a Hitachi7600-210 biochemical an-alyzer,and serum total bilirubin(TBIL)and direct bilirubin(DBIL)levels were determined.The mitotic index(MI)and proliferating cell nuclear antigen(PCNA)positivity in liver tissues were examined.Enzyme-linked immunosorbent assay(ELISA)was used to detect plasma levels of tumor necrosis factor(TNF-α),interleukin(IL)-1β,IL-10,and IL-6 in rats from each group.Kits were employed to measure superoxide dismutase(SOD),glutathione(GSH),and malondialdehyde(MDA)contents in liver tissues of rats from each group.The TUNEL method was adopted to detect hepatocyte apoptosis rates in liver tissues,and immunoblotting was used to assess the expression of phosphorylated extracellular signal-regulated kinase 1/2(p-ERK1/2)and extracellular signal-regu-lated kinase 1/2(ERK1/2)proteins in liver tissues.Results Compared with the control group,the model group exhibited increased p-ERK1/2 protein expression(P＜0.05).Compared with the model group,both the low-dose and high-dose groups showed decreased p-ERK1/2 protein expres-sion(P＜0.05).The model group had an increased hepatocyte apoptosis index compared with the control group(P＜0.05).Both the low-dose and high-dose groups demonstrated decreased hepato-cyte apoptosis indices compared with the model group(P＜0.05).Compared with the control group,the model group had increased MDA levels and decreased SOD and GSH levels(P＜0.05).Both the low-dose and high-dose groups exhibited decreased MDA levels and increased SOD and GSH levels compared with the model group(P＜0.05).The model group showed increased levels of TNF-α,IL-1β,IL-10,and IL-6 compared with the control group(P＜0.05).Both the low-dose and high-dose groups had decreased levels of TNF-α,IL-1 β,IL-10,and IL-6 compared with the model group(P＜0.05).Compared with the control group,the model group had decreased MI and PCNA positivity rates(P＜0.05).Both the low-dose and high-dose groups exhibited increased MI and PCNA positivity rates compared with the model group(P＜0.05).The model group had in-creased AST,ALT,γ-GT,TBIL and DBIL values compared with the control group(P＜0.05).Both the low-dose and high-dose groups showed decreased AST,ALT,γ-GT,TBIL and DBIL val-ues compared with the model group(P＜0.05).Conclusion Tanshinone ⅡA may alleviate D-GalN-induced acute liver failure in rats through the ERK1/2 signaling pathway.

Objective To investigate the effects of microgravity environment on hibernating myoblasts.Methods Hibernating myoblasts were cultured under real and simulated microgravity conditions for 10 days.RNA-seq analysis and immunofluorescence are used to analysis the impact of microgravity environment on cell growth and gene expression of myoblasts.Results Under the microgravity conditions,genes associated with proliferation were upregulated.Under simulated microgravity,there were more and higher proportion of Ki67 positive cells compared to normal gravity conditions.Conclusion The microgravity environment promotes the proliferation of hibernating myoblasts.

BACKGROUND: The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex. METHODS: The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases. RESULTS: WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group. CONCLUSIONS This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.
Animals ; Mice ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Liver Neoplasms/genetics*

Guideline or consensus for the vaccination of children with special conditions like immunocompromised children may be more suitable for pediatricians.However, the vaccination of children in China is mainly performed by general practitioners or child health care practitioners in community health service centers.They need to master the screening knowledge of contraindications and precautions for the vaccination of children, and make the decision to referral to specialists.Based on the technical guidelines for Immunization of National Health Commission of the People′s Republic of China, Best Practices Guidance of the Advisory Committee on Immunization Practices and contraindications and precautions proposed by the Immunization Action Coalition, 20 suggestions for primary screening of children with vaccination contraindications and referral recommendations for primary care providers were developed by experts from the Integration of Medicine and Prevention in Children of Health Commission of Shenzhen Municipality.

Objective:To explore the clinical manifestations and imaging features of nocardia infection (NI) after lung transplantation and boost the diagnosis and treatment of NI.Methods:From January 2018 to December 2019, basic profiles, clinical manifestations, laboratory examinations, imaging features and treatment outcomes of 5 lung transplant recipients with a diagnosis of NF were retrospectively analyzed and summarized with the relevant literatures. There were 4 males and 1 female with a median age of 66(26-69) years. 3 patients were single-lung transplantation, 2 patients were bilateral-lung transplantation. The median time from an initial diagnosis of NI to lung transplant surgery was 6(5-19) months. Common symptoms included fever, cough with yellow phlegm and shortness of breath. Laboratory findings showed lymphopenia, significantly high C-reactive protein levels, a slight elevation of procalcitonin, hypoproteinemia and anemia. The major manifestations of high-resolution computed tomography (CT) included multiple nodules, consolidation, cavitation and pleural effusion.Results:Five strains of N. farcinica were identified from bloodstream infection ( n=2) and pulmonary infection ( n=3). After with a combined therapy of two sensitive agents, all patients improved and were discharged from hospital. During follow-ups, one patient died and the remainders were cured. Conclusions:Nocardia infection occurs in lung transplant recipients mostly within 1 year post-operation. There are non-specific symptoms and imaging features of multiple nodules and consolidation. Combination therapy of sensitive agents is indicated for lung transplant recipients with NI.

Objective:To explore the incidence, clinical characteristics and prognosis of invasive pulmonary fungal infection(IPFI)in recipients of lung transplantation(LT)in southern China.Methods:From January 2003 to August 2019, retrospective analysis was performed for 300 recipients of lung transplantation at three hospitals in southern China. There were 254 males and 46 females with an average age of (54.98±14.2)years. Clinical data were collected from medical records, including symptoms and signs, imaging studies, bronchoscopy examination, pathogen separation and culture from deep sputum and bronchoalveolar lavage fluid(BALF), fungal-related laboratory tests and tissue pathology.Results:Among 300 cases, 93(31.0%)had at least one episode of IPFI. The most common pathogen was aspergillosis(60.2%), followed by candida(15 cases, 16.1%)and Pneumocystis jeroveci (13 cases, 14.0%). Kaplan Meier analysis indicated that all-cause mortality was significantly higher in IPFI group than that in non-IPFI(nIPFI)group with one-year mortality of 45.2% vs. 26.7% in IPFI and nIPFI groups respectively( P<0.05). Conclusions:IPFI is prevalent after LT in southern China. And aspergillosis is the most common pathogen and Candida comes the next. The median occurring time for aspergillosis is 6 months after LT. Candida infection occurs earlier at airway anastomosis. A higher incidence of invasive fungal disease(IFD)associated with a lower survival indicates that IPFI has a substantial mortality among recipients after LT. Prophylactic agents should be optimized based upon an epidemiologically likely pathogen.

Objective To analyze the risk factors and clinical prognosis of acute kidney injury (AKI) early after lung transplantation. Methods Clinical data of 155 recipients undergoing lung transplantation or combined heart-lung transplantation were retrospectively analyzed, and they were divided into the AKI group (n=104) and non-AKI group (n=51) according to the 2012 Kidney Disease: Improving Global Outcomes Clinical Practice Guideline. The incidence of AKI early after lung transplantation was summarized. The main indexes of recipients were collected. The risk factors of the occurrence of AKI early after lung transplantation were subjected to univariate and multivariate analysis. The clinical prognosis of lung transplant recipients was evaluated and the survival curve was delineated. Results The incidence of AKI early after lung transplantation was 67.1%(104/155), including 47 recipients with stage 1 AKI, 34 recipients with stage2 AKI and 23 recipients with stage 3 AKI, respectively. Sixteen recipients required continuous renal replacement therapy (CRRT) early after lung transplantation. Preoperative complication with diabetes mellitus, preoperative complication with pulmonary hypertension, intraoperative mean arterial pressure (MAP) < 60 mmHg, intraoperative massive blood transfusion, and treatment with excessive therapeutic concentration of tacrolimus (Tac) within postoperative 1 week were the independent risk factors for the occurrence of AKI early after lung transplantation. Up to the end of follow-up, 66 recipients (42.6%) died, including 50 recipients in the AKI group and 16 recipients in the non-AKI group. The cumulative survival rate in the AKI group was significantly lower than that in the non-AKI group (40% vs. 66%, P < 0.05). With the increase of AKI severity, the cumulative survival rate of lung transplant recipients was decreased. Conclusions AKI develops early after lung transplantation with high incidence and poor clinical prognosis. Preoperative complication with diabetes mellitus and pulmonary hypertension, intraoperative MAP < 60 mmHg and massive blood transfusion, and treatment with excessive therapeutic concentration of Tac within postoperative 1 week are the independent risk factors for the occurrence of AKI early after lung transplantation.

Acute cellular rejection (ACR) is a common complication after lung transplantation, which is mainly caused by the immune response of T lymphocytes recognizing the major histocompatibility complex on the cellular surface of grafts. It is currently considered as the main pattern of acute rejection. ACR is not only a direct cause of death of recipients, but also a high-risk factor for chronic rejection after lung transplantation. Nevertheless, it is a challenging task to deliver the diagnosis and treatment of ACR following lung transplantation. In this article, new progresses on the risk factors, pathogenesis, diagnosis and treatment of ACR in lung transplant recipients were summarized, aiming to improve the diagnostic and treatment efficiency of ACR and prolong the survival of recipients.

Objective To analyze the dynamic changes and the influencing factors of T lymphocyte subsets in recipients with stable graft status within 1 year after lung transplantation. Methods Clinical data of 41 recipients with stable graft status after allogeneic lung transplantation were analyzed. The absolute value and ratio of T lymphocyte subsets in peripheral blood from recipients were measured by flow cytometry before operation, 2 weeks and each month (within 1 year) after operation, respectively. The effects of age, gender, body mass index (BMI), surgical method, incidence of primary graft dysfunction (PGD) after operation, and primary disease upon the absolute values of T lymphocytes were evaluated. Results Within 1 year after lung transplantation, the absolute values of CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺T lymphocytes and CD4⁺/CD8⁺ ratio were changed over time (all P < 0.001). Compared with preoperative values, there was no statistical significance in the absolute values of CD3⁺ and CD3⁺CD4⁺T lymphocytes at 12 months after operation (P=0.659, 0.109), whereas the absolute value of CD3⁺CD8⁺T lymphocytes was increased (P=0.02) and the CD4⁺/CD8⁺ ratio was decreased (P < 0.001). Age, gender, BMI, surgical method and incidence of PGD after operation exerted no significant effect on the dynamic changes of absolute values of CD3⁺CD4⁺ and CD3⁺CD8⁺T lymphocytes (all P > 0.05). Primary disease before lung transplantation exerted no effect on the changes of CD3⁺CD4⁺T lymphocytes, whereas the postoperative absolute value of CD3⁺CD8⁺T lymphocytes was higher in recipients with infectious lung diseases (P < 0.05). Conclusions The absolute values of CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺T lymphocytes in recipients with stable graft status after lung transplantation are relatively low in the early stage after lung transplantation, then gradually restore, and stabilize at 6 months after operation. Dynamic changes are not associated with age, gender, BMI, surgical method and incidence of PGD after operation of recipients.

Objective:To explore the significance of US lung allocation score (LAS) in Chinese lung transplant recipients.Methods:The clinical data were analyzed for 173 lung recipients from May 2005 to March 2018. The LAS of each patient was calculated by an online LAS calculator of Organ Procurement and Transplantation Network (OPTN).Results:The mean age was (56.49±12.64) years and the mean LAS (56.63±18.39)(32.79-90.70). The underlying diseases were chronic obstructive pulmonary disease (COPD, n=62), interstitial lung disease (n=85), bronchiectasis (n=11), pulmonary arterial hypertension (n=8) and others (n=7). And the value of LAS was (47.85±15.22) vs. (61.89±18.63) vs. (56.58±18.91) vs. (55.23±10.74) vs. (72.45±16.41). LAS of COPD patients was significantly lower than that of interstitial lung disease ( P<0.001). Mean LAS was the highest in endotracheal intubation or ECMO group (79.15±7.95), then non-invasive ventilation group (48.42±11.58) and lowest in oxygen inhalation group (44.11±8.81)( P<0.001). Recipients were divided into three groups of LAS <50 for low-risk, 50-75 for moderate-risk and >75 for high-risk. Survivals at 90 days and 1 year were 90.5% vs. 81.8% vs. 71.1% and 85.4% vs. 74.4% vs. 57.8% ( P=0.002). Conclusions:LAS can not only reflect the urgency of recipients waiting for lung transplantation but also predict postoperative period. LAS score should be employed for selecting suitable lung transplant recipients in China and the optimal LAS lies between 30 and 75.