The clinical data of a WHIM syndrome child with cardiac malformation as the first symptom in December 2017 in Beijing Children′s Hospital Affiliated to Capital Medical University was retrospectively analyzed.A 5-year-old female patient presented with cardiac malformation, neutropenia and recurrent infection.Heterozygous mutation(c.1000C>T) was detected in CXCR4 gene.Echocardiography and CT exhibited cardiac malformation.WHIM syndrome is very rare, and it was the first case with cardiac malformation as the first manifestation in China, thus hoping to improve clinicians′ understanding of this disease.

Objective To evaluate effects of artesunate on rosacea-like inflammation in mouse models.Methods Twenty-five male BALB/c mice aged 7 weeks were injected subcutaneously with 40 μ1 antibacterial peptide LL-37 into the back once every 12 hours for 4 sessions to establish mouse models with rosacea-like inflammation.These 25 mice were randomly and equally divided into 5 groups:after each injection of LL-37,model group were gavaged with sodium chloride physiological solution,treatment groups gavaged with 25,50 and 100 mg/kg artesunate solution separately,and positive control group gavaged with 30 mg/kg doxycycline hydrochloride solution.Another 5 healthy mice injected subcutaneously with pure water into the back for 4 sessions served as blank control group.Forty-eight hours after the initial injection of LL-37,changes in skin lesions and the intensity of erythema were assessed.Skin tissues at the dorsal injection site were resected and subjected to HE staining,the tissue structure was observed and the number of inflammatory cells was counted.Enzyme-linked immunosorbent assay (ELISA) was performed to estimate the activity of myeloperoxidase (MPO) in skin lesions.Results The model group showed obvious inflammatory reactions,and significantly increased erythema score (3.20 ± 0.84),inflammatory cell count (517.27 ± 99.43) and MPO activity (0.57 ± 0.08) compared with the blank control group (all P ＜ 0.01).The positive control group showed significantly decreased erythema score (1.60 ± 0.89),inflammatory cell count (270.93 ± 124.63) and MPO activity (0.40 ± 0.05) compared with the model group (P ＜ 0.05,0.01,0.01,respectively).Moreover,the erythema score,inflammatory cell counts and MPO activity were all significantly lower in 50-(1.80 ± 0.84,286.00 ± 33.72,0.43 ± 0.05,respectively) and 100-mg/kg artesunate groups (1.40 ± 0.55,258.00 ± 36.44,0.40 ± 0.06,respectively) than in the model group (P ＜ 0.05 or 0.01).However,there were no significant differences in the erythema score,inflammatory cell count and MPO activity between 50-or 100-mg/kg artesunate group and the positive control group (P ＞ 0.05).Conclusion Artesunate can inhibit rosacea-like inflammatory reactions in mouse models,especially the middle-and high-dose artesunate.

BACKGROUND:Nanocomposite hydrogel has great research prospects and application potential in the treatment of osteoarthritis. OBJECTIVE:To review the research progress of nanocomposite hydrogel in osteoarthritis and cartilage repair. METHODS:Databases such as CNKI and PubMed were searched.The English key words were"nanocomposite hydrogel,nanogel,osteoarthritis,cartage,physical encapsulation,electrostatic interaction,covalent crosslinking",and the Chinese key words were"nanocomposite hydrogel,nanogel,osteoarthritis,cartage,physical encapsulation,physical encapsulation,electrostatic effect,covalent cross-linking".After an initial screening of all articles based on inclusion and exclusion criteria,71 articles with high correlation were retained for review. RESULTS AND CONCLUSION:In cell or animal experiments,nanocomposite hydrogel has the effect of improving osteoarthritis.Nanocomposite hydrogel can promote cartilage repair,improve the internal environment of osteoarthritis,and achieve the therapeutic purpose of osteoarthritis by improving the mechanical environment between joints,carrying targeted drugs,and promoting the chondrogenesis of seed cells.At present,the research of nanocomposite hydrogel in osteoarthritis disease still has a huge space to play.It is expected to open up a new way for the clinical treatment of osteoarthritis by continuing to deepen the research of material preparation and actively carrying out cell and animal experiments.

AIM: To investigate the role of sorafenib in promoting ferroptosis in HCC, and whether cell death can be induced by activating mitochondrial oxidative stress and consequent mitochondrial dysfunction. METHODS: Hepatocellular carcinoma cell lines Huh7 and HCC-LM3 were treated with different concentrations of sorafenib, the cell viability was determined by CCK-8 assay; mitochondrial membrane potential (MMP) was measured by Tetramethylrhodamine (TMRM) staining; The mitochondrial oxygen consumption rate was monitored by the Seahorse XF24 Analyzer; mitochondrial superoxide indicator (Mitosox) was used to determine the level of reactive oxygen species (ROS) in mitochondria; the formation of total ROS was determined by dichlorofluorescein diacetate (DCF-DA) staning. Finally, The recovery of oxidative damage and cell death induced by sorafenib was observed after pretreated by glutathione (GSH). RESULTS: With the increasing concentration of sorafenib, the survival of the Huh7 and HCC-LM3 was significantly decreased. Sorafenib also inhibited the oxygen consumption rate and decreased oxidative phosphorylation, which results in the depolarization of MMP, ROS accumulation and eventually ferroptosis of HCC cells. However, the occurrence of oxidative stress induced by sorafenib in HCC cells can be effectively reversed by the pretreatment of GSH. CONCLUSION: The ferroptosis can be induced by sorafenib through inducing mitochondrial dysfunction and ROS accumulation in HCC cells. However, the GSH can restore oxidative damage. Therefore, induction of the GSH deficiency in HCC may be a potential therapeutic option to enhance the efficacy of sorafenib.

Objective    To investigate the status quo and influencing factors of depression and anxiety in postoperative patients with thoracic neoplasms. Methods    The general information questionnaire and Huaxi emotional-distress index scale (HEI) were adopted to survey 70 patients after surgery of thoracic neoplasms at the thoracic nursing outpatients from September to November 2016. There were 43 males and 27 females with age of 18-78 (56.20±11.34) years. Results    The prevalence rate of depression and anxiety among postoperative patients with thoracic neoplasms was 50.0%, and moderate to severe negative emotions predominated. There was significant difference in educational levels, postoperative hospitalization and postoperative complications (P<0.05), while no significant difference in age, gender, disease types, complicated diseases, surgical procedures, pathological stages and hospitalization expenditures between patients with unhealthy emotions and normal emotions (P>0.05). Conclusion    There is a high prevalence rate of negative emotion among postoperative patients with thoracic neoplasms. Educational levels, postoperative hospitalization and postoperative complications are important factors for negative emotion.

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.