TIPE3 protects mice from lipopolysaccharide-induced acute lung injury.

BACKGROUND: Acute lung injury (ALI) is a severe inflammatory disease with high morbidity and mortality in patients and lung transplant recipients. Tumor necrosis factor-α-induced protein 8-like 3 (TIPE3) is one of the members of the TIPE family. While TIPE2 has been demonstrated to be protective against lipopolysaccharide (LPS)-induced ALI, the role of TIPE3 in ALI is currently unidentified. METHODS: To examine the role of TIPE3 in ALI, we pretreated C57BL/6 mice with control or TIPE3-lentivirus in LPS-induced ALI models. The C57BL/6 mice were randomly divided into four groups: control group; ALI-induced group; ALI-induced group with control lentivirus; and ALI-induced group with TIPE3-lentivirus. Additionally, RAW 264.7 cells were used to validate the role and molecular mechanism of TIPE3 signaling in vitro. RESULTS: An increased expression of TIPE3 reduced lung histopathological damage in ALI-affected mice. ALI-affected mice treated with TIPE3-lentivirus exhibited reduced lung microvascular permeability, myeloperoxidase (MPO) activity, neutrophil buildup, and inflammation response. Additionally, over-expression of TIPE3 significantly inhibited NF-κB activation and promoted the activation of Liver X receptors alpha (LXRα). In LPS-treated RAW264.7 cells, enforced TIPE3 expression produced anti-inflammatory effects, whereas the LXR inhibitor geranylgeranyl pyrophosphate (GGPP) reversed these effects. CONCLUSIONS: TIPE3 protected against LPS-induced ALI by regulating the LXRα/NF-κB signaling pathway. These results suggest that TIPE3 might provide a novel insight into the prevention of ALI.

[Prevalence Rate and Risk Factors of Hypothyroidism in Children with Beta Thalassemia Major in Zhuhai Area].

OBJECTIVE: To investigate the prevalence rate of hypothyroidism in children with ß-thalassemia major (ß-TM) and its risk factors. METHODS: A total of 86 children with ß-TM treated and followed up in the Department of Pediatrics of the Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai Municipal Maternal and Child Health Care Hospital from August 2018 to August 2020 were enrolled. The clinical data of the children were analyzed to investigate the prevalence rate of hypothyroidism in children with ß-thalassemia major (ß-TM) and its risk factors. RESULTS: The prevalence rate of hypothyroidism in children with ß-TM in Zhuhai area was 17.4%. The level of serum ferritin(SF) (4948.27±1225.33 µg/L) in hypothyroidism children was significantly increased(t=10.273，P<0.05). The prevalence rate of hypothyroidism was significantly higher in ß-TM children(age ≥10 years old, SF ≥2 500 µg/L and irregular iron removal) (P<0.05). Logistic regression result showed that age ≥10 years old was the independent risk factor affecting the increasing of hypothyroidism rate in the children. The levels of SF(3880.60±1269.17 µg/L), TSH(4.43±1.52 mIU/L) and the prevalence rate of hypothyroidism(37.14%)(P<0.05) were higher for the children in irregular iron removal group. CONCLUSION: The prevalence rate of hypothyroidism in children with ß-TM in Zhuhai area is high, and it is related to the age ≥10 years old, SF ≥2 500 µg/L and irregular iron removal of the children.

A Child Infected with COVID-19 in China-A Case Report.

A 16-month-old boy was admitted with cough for 2 days and fever for 1 day. Chest computed tomography (CT) scan of the child revealed large areas of ground-glass opacities in both lungs. Nucleic acid amplification tests (NAATs) were performed repeatedly to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the results were all negative. On day 13 of hospitalization, no clinical symptoms except diarrhea were present in the patient, and re-examination by chest CT revealed lesion shrinkage, but the NAAT on throat swabs was positive. On day 22 of hospitalization, the NAAT on throat swabs was negative and the fecal samples were positive. Positive fecal samples nucleic acid lasted for 62 days. Suggesting that pediatric patients may be important sources of infection during the recovery phase of clinical symptoms and whether SARS-CoV-2 has fecal-oral transmission needs further study.

Efficacy and safety of eltrombopag in the treatment of Chinese children with chronic immune thrombocytopenia.

OBJECTIVES: Our aim is to evaluate initial efficacy, safety, and durable response of eltrombopag in the treatment of Chinese children with chronic immune thrombocytopenia (cITP). METHODS: This was a retrospective, single-center cohort study including 30 pediatric patients with cITP administered eltrombopag between 1 July 2017 and 1 January 2019. Patients with at least 12 weeks of eltrombopag treatment and available follow-up data were included. Initial response rate, durable response rate, bleeding events, and adverse events were assessed during the follow-up period. RESULTS: The median duration of eltrombopag administration was 6 months (range 3-8 months). The initial response rate was 73.3%. Patients with megakaryocyte count ≥100/slide or Treg <4.5% were more likely to achieve initial response. The median follow-up period was 10 months (range 6-20 months). A total of 53.2% of pediatric patients had a durable response of up to 20 months. Patients with megakaryocyte count ≥100/slide and Treg<4.5% had more than 60% durable response rates compared with individuals with megakaryocyte count<100/slide and Treg≥4.5%, respectively. No serious bleeding events or serious adverse events occurred during the study period. CONCLUSION: Eltrombopag not only shows excellent initial response but also has continued efficacy and safety. Patients with megakaryocyte count ≥100/slide and Treg<4.5% achieve increased initial response and more frequent durable response.

20(S)-Ginsenoside Rh2 displays efficacy against T-cell acute lymphoblastic leukemia through the PI3K/Akt/mTOR signal pathway.

BACKGROUND: T-cell acute lymphoblastic leukemia (T-ALL) is a kind of aggressive hematological cancer, and the PI3K/Akt/mTOR signaling pathway is activated in most patients with T-ALL and responsible for poor prognosis. 20(S)-Ginsenoside Rh2 (20(S)-GRh2) is a major active compound extracted from ginseng, which exhibits anti-cancer effects. However, the underlying anticancer mechanisms of 20(S)-GRh2 targeting the PI3K/Akt/mTOR pathway in T-ALL have not been explored. METHODS: Cell growth and cell cycle were determined to investigate the effect of 20(S)-GRh2 on ALL cells. PI3K/Akt/mTOR pathway-related proteins were detected in 20(S)-GRh2-treated Jurkat cells by immunoblotting. Antitumor effect of 20(S)-GRh2 against T-ALL was investigated in xenograft mice. The mechanisms of 20(S)-GRh2 against T-ALL were examined by cell proliferation, apoptosis, and autophagy. RESULTS: In the present study, the results showed that 20(S)-GRh2 decreased cell growth and arrested cell cycle at the G1 phase in ALL cells. 20(S)-GRh2 induced apoptosis through enhancing reactive oxygen species generation and upregulating apoptosis-related proteins. 20(S)-GRh2 significantly elevated the levels of pEGFP-LC3 and autophagy-related proteins in Jurkat cells. Furthermore, the PI3K/Akt/mTOR signaling pathway was effectively blocked by 20(S)-GRh2. 20(S)-GRh2 suppressed cell proliferation and promoted apoptosis and autophagy by suppressing the PI3K/Akt/mTOR pathway in Jurkat cells. Finally, 20(S)-GRh2 alleviated symptoms of leukemia and reduced the number of white blood cells and CD3 staining in the spleen of xenograft mice, indicating antitumor effects against T-ALL in vivo. CONCLUSION: These findings indicate that 20(S)-GRh2 exhibits beneficial effects against T-ALL through the PI3K/Akt/mTOR pathway and could be a natural product of novel target for T-ALL therapy.

Daily sedentary time and its association with risk for colorectal cancer in adults: A dose-response meta-analysis of prospective cohort studies.

Sedentary behavior is emerging as an independent risk factor for health. However, previous studies have indicated that sedentary behaviors are associated with the colorectal cancer risk, but presented controversial results.Studies in PubMed and EMBASE were searched update to February 2017 to identify and quantify the potential dose-response association between daily sedentary time and colorectal cancer.Twenty-eight eligible studies involving a total of 47,84,339 participants with 46,071 incident cases were included in this meta-analysis. Our results showed statistically significant association between prolong television viewing time and colorectal cancer (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.09-1.24, P < .001). Additionally, we obtained the best fit at an inflection point of 2 hours per day in piecewise regression analysis, the summary relative risk (RR) of colorectal cancer for an increase of 2 hours per day television viewing was 1.07 (95% CI 1.05-1.10, P < .001). Furthermore, prolong occupational sitting time was correlated with a significantly higher risk of colorectal cancer (OR 1.15, 95% CI 1.08-1.22, P < .001), increasing 2 hours per day of occupational sitting time per day was associated with a 4% incremental in the risk of colorectal cancer (RR 1.04, 95% CI 1.01-1.08). Additionally, prolong total sitting time was associated with a significantly higher risk of colorectal cancer (OR 1.06, 95% CI 1.03-1.09, P < .001). Increasing 2 hours of total sitting time per day was associated with a 2% incremental in the risk of colorectal cancer (RR 1.02, 95% CI 1.01-1.06). Subgroup meta-analyses in study design, study quality, number of participants, and number of cases showed consistent with the primary findings.Prolonged television viewing, occupational sitting time, and total sitting time are associated with increased risks of colorectal cancer.

Ginsenoside Rh2 and Rg3 inhibit cell proliferation and induce apoptosis by increasing mitochondrial reactive oxygen species in human leukemia Jurkat cells.

Ginsenoside Rh2 (GRh2) and ginsenoside Rg3 (GRg3) are primary bioactive components in Panax ginseng. The present study aimed to investigate the underlying mechanisms of apoptotic cell­death induced by GRh2 and GRg3 in human leukemia Jurkat cells. The Cell Counting kit­8 assay was used to determine cell proliferation. Apoptosis was detected by nuclear morphologic observation by Hoechst 33342 staining and Annexin V-allophycocyanin and 7-amino-actinomycin D assay. mitoTEMPO, a mitochondrial reactive oxygen species (ROS) scavenger, was used to examine the effects of mitochondrial ROS on cell viability and mitochondrial membrane potential (MMP). Finally, the expression levels of numerous mitochondrial­associated apoptosis proteins were assessed by western blot analysis. These results demonstrated that GRh2 and GRg3 inhibited cell growth and induced apoptosis, and that GRh2 had greater cytotoxicity than GRg3. GRh2 induced generation of more mitochondrial ROS compared with GRg3 in Jurkat cells; however, this effect was ameliorated by subsequent treatment with mitoTEMPO. Furthermore, excess mitochondrial ROS induced by GRh2 was more potent than GRg3 in inhibiting cell proliferation and reducing MMP. In addition, expression levels of apoptosis­associated proteins were significantly increased in Jurkat cells treated with GRh2 than GRg3. In conclusion, these findings suggested that GRh2 and GRg3 induce mitochondrial-associated apoptosis by increasing mitochondrial ROS in human leukemia Jurkat cells. GRh2 may more effectively inhibit cell growth and accelerate apoptosis than GRg3. This study provides a potential novel strategy for the treatment of acute lymphoblastic leukemia.