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Interleukin 33 (IL‐33) and soluble form of ST2 (sST2) are involved in inflammation. This study aimed to assess the role of serum IL‐33 and sST2 in neonates with HCMV infection. The concentration of serum IL‐33 and sST2 in 20 patients and 16 healthy controls were measure by enzyme‐linked immune‐sorbent assay (ELISA). The clinical and laboratory data were described. Our results showed serum sST2 and IL‐33 levels were significantly higher in the HCMV group than the control group. Significant positive correlation was observed between sST2 and IL‐33 (r = 0.518, P = 0.001). Furthermore, there was a positive, moderate, and statistically significant correlation between sST2 and ALT levels in the control and HCMV groups (r = 0.579, P = 0.007; r = 0.66, P = 0.005, respectively). The AUC of sST2 and IL‐33 was found to be 0.822 and 0.867 respectively. Further, at a cut‐off value of 1823.4 ng/mL, sST2 gave 65% sensitivity and 93.7% specificity. Similarly, IL‐33 gave 95% sensitivity and 68.7% specificity at a cut‐off value 2.04 pg/mL. The Youden index of sST2 and IL‐33 was found to be 0.587 and 0.637, respectively. In conclusion, this study revealed that sST2 and IL‐33 have great potential to be used as biomarkers for early screening and indicate liver damage for HCMV patients in future after validation in large cohort study. [ABSTRACT FROM AUTHOR]

Context: Intravenous immunoglobulin (IVIG) has been successfully applied in immune-related diseases of adults and neonates, such as human immunodeficiency virus (HIV) infection and systemic lupus erythematosus (SLE). Objective: This study aims to investigate the distinct impacts of IVIG on cultured dendritic cells (DCs) from newborn and healthy adult. Materials and methods: Blood samples were collected from eight full-term newborns and eight healthy adult volunteers. DCs from cord blood and peripheral blood were both cultured in the RPMI 1640 medium containing 10% fetal calf serum, 50 ng/ml granulocyte/macrophage colony-stimulating factor (GM-CSF) and 10 ng/ml recombinant human interleukin-4 (rhIL-4) for 5 d with therapeutic IVIG (20 mg/ml) or physiological IVIG (10 mg/ml). Lipopolysaccharides (LPSs, 1 μg/ml) were added on the fifth day to induce the maturation of immature DCs. The phagocytosis of monocytes, expression of MR (mannose receptor), CD14, CD1a, CD80, CD83, CD86 and MHC II were examined by flow cytometry. The expression of IL-4 mRNA was detected by RT-PCR, while IFN-γ, IL-12 and IL-10 were analyzed by enzyme-linked immunosorbent assay (ELISA) commercial kits. Results: IVIG of therapeutic dose inhibited the phagocytosis, differentiation and maturation of DCs, whereas physiological dose exhibited an accelerated role in vitro, especially on DCs from neonates, but aroused different effects on cytokine secretion. Discussion and conclusion: The different responses are generally due to immature immune system of neonate, which has a limit capacity to maintain immunity homeostasis. Modulation of DCs phagocytosis, differentiation, maturation and cytokine secretion by IVIG is of potential relevance to its dosage and immune status of patients. [ABSTRACT FROM AUTHOR]

A Content, Context, Connection and Researching, Reasoning, Reflecting (3C3R) model is a conceptual framework for problem-based learning (PBL) problem design. We introduced the 3C3R-PBL method into a pediatric teaching plan, and evaluated its effectiveness and feasibility. The 3C3R model was applied in a pediatric problem design teaching plan “why the lips turn purple when a baby is crying”. All students were assigned either into a traditional PBL course or into a 9-step 3C3R model PBL course (3C3R-PBL). The performance outcomes of both groups were compared. For the PBL group, the proportion of students scoring ≥4 for content, context, and problem design connection, was 90.8%, 80.3%, and 64.5% respectively, while for tutors, it was 71.4%, 71.4%, and 28.6%; for researching, reasoning, and reflecting, the proportion of students scoring ≥4 was 81.6%, 55.3%, and 40.8%, while for tutors, it was 71.4%, 100%, and 57.1%. The learning difficulty was not considered high with only 31.6% of students and 42.9% of tutors rating the task as difficult. For the 3C3R-PBL group, the proportion of students scoring content, context, and connection, ≥4 was 100%, 98.4%, and 90.5%, while for tutors it was 100%, 100%, 83.3%; for researching, reasoning, and reflecting, the proportion of students scoring ≥4 was 95.2%, 88.9%, and 76.2%, while for tutors it was 100% for all 3 R components. Students and tutors were convinced by the content, case context, research process and reasoning process of both teaching plans, while scores for connection and reflecting were significantly improved when the PBL plan was amended by a 3C3R model (p<0.05) and the case learning difficulty was statistically increased (p<0.05). The 3C3R model, evaluated for the first time in China, was helpful for effective and reliable problem design in a pediatric PBL teaching plan for Chinese students. [ABSTRACT FROM AUTHOR]

Highlights: [•] We examined the change of IL-10 receptor expression in MRC-5 cells under different conditions. [•] IL-10 inhibits autophagy in MRC-5 cells induced by HCMV infection. [•] HCMV replications are repressed when autophagy is inhibited by IL-10 treatment. [Copyright &y& Elsevier]

Through a comprehensive analysis on the fundamental theory of the equivalent static wind load (ESWL), it is pointed out that the ESWL derived from the wind-induced vibration factor in Chinese Load Code will lead to the equivalent results for all the load effects provided that only the first vibration mode needs to be considered. But on the condition that several vibration modes are involved, the ESWL satisfying all the load effects doesn' t exist unless these modes are completely correlated. So in general cases, an ESWL given by different analysis methods including the gust loading factor method is only effective for one or more specific equivalent targets. Other load effects may be overestimated or underestimated under the action of such ESWL. In order to overcome the limit of the conventional methods, a new approach was proposed to make wind-resistant design based on load effects. The envelope of various load effects was obtained first through wind tunnel tests and it was combined directly with the corresponding effects induced by other loads. This design method was demonstrated by an engineering case. It is shown that the ESWL derived from the gust loading factor overestimated significantly some load effects while the wind-resistant design using the load effects envelop is accurate and convenient to carry out. [ABSTRACT FROM AUTHOR]

An analysis method was proposed to derive the equivalent static wind load (ESWL) on the large-span spatial structures on the basis of the instantaneous wind pressure at specific time. The response time history was resolved firstly by generalized coordinates synthesis method and the time at which the response reaches its extreme was identified. As long as the dynamic amplification factor or the additional wind-induced vibration force was imposed on the instantaneous wind pressure at that time, the ESWL corresponding to the extreme response could be obtained accordingly. The combination of the instantaneous wind pressure and the additional wind-induced vibration force can result in a reasonable ESWL which acts along the different direction with the surface wind pressure and thus avoid overestimating the ESWL at some situations. Moreover for the convenience of the engineering application, the quasistatic component and additional wind-induced vibration force were thoroughly separated according to the accurate formula of the ESWL and the simplified estimation of the additional wind-induced vibration force was also proposed. The validity of the method was demonstrated by the case study on a large-span structure. Under the action of the ESWL derived by the method, the equivalence of the target response is achieved and other responses also agree with the actual responses. [ABSTRACT FROM AUTHOR]

Osteopetrosis is a genetic condition of the skeleton characterized by increased bone density caused by osteoclast formation and function defects. Osteopetrosis is inherited in the form of autosomal dominant and autosomal recessive manner. We report autosomal recessive osteopetrosis (ARO; OMIM 611490) in a Chinese case with a history of scarce leukocytosis, vision and hearing loss, frequent seizures, and severe intellectual and motor disability. Whole-exome sequencing (WES) followed by Sanger sequencing revealed novel compound heterozygous mutations in the chloride channel 7 ( CLCN7 ) gene [c.982-1G > C and c.1208G > A (p. Arg403Gln)] in the affected individual, and subsequent familial segregation showed that each parent had transmitted a mutation. Our results confirmed that mutations in the CLCN7 gene caused ARO in a Chinese family. Additionally, our study expanded the clinical and allelic spectrum of the CLCN7 gene and enhanced the applications of WES technology in determining the etiology of prenatal diagnoses in fetuses with ultrasound anomalies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Wang, Wang, Xu, Fan, Ding and Qian.)

Bronchopulmonary dysplasia (BPD) is the most common complication in preterm newborns. It occurs due to early exposure to high-oxygen and ventilation therapy. The mechanisms of disrupted alveolarization and vascular development associated with BPD were unclear. Deferoxamine (DFO) has been reported to reduce mortality and lung injury in mice after chlorine exposure. The effect of DFO in the treatment of BPD has not been explored. This study aimed to investigate the effect of aerosolized DFO administration in a mouse model of BPD. A mouse model of oxygen-induced BPD was established by postnatal hyperoxia (75% oxygen for 7 days) and DFO [17 mg/(kg·day)] (BPD+D) or aerosolized vehicle (BPD+V) administered for 14 days. The mice were anesthetized and sacrificed after 14 days treatment before removing the lungs for analysis. An exogenous continuous aerosol of DFO exerted a biological effect on BPD mice. The BPD+DFO group showed a better weight gain compared with the BPD+V group. Furthermore, the treatment of DFO exhibited a reduced pathological severity and increase expression of hypoxia-inducible factor (HIF)-1α and CD31, and activated downstream vascular endothelial growth factor (VEGF)-induced angiogenesis. The results showed that C57BL/6 mice exposed to hyperoxic environment and treated with aerosolized of DFO solution, obviously promoted the pulmonary vascularization and alveolarization. The HIF-1α/VEGF signaling pathway mediated this process. The findings indicated that treatment with an exogenous continuous aerosol of DFO might be a potential therapeutic strategy for BPD., Competing Interests: None.

Neuroblastoma (NB) is one of the most common tumors in childhood. Unfortunately, the survival outcomes remain unsatisfactory since NB commonly develops multidrug resistance. Recent studies have demonstrated that the high mobility group box 1 (HMGB1)-mediated autophagy promotes chemoresistance in osteosarcoma, lung adenocarcinoma and ovarian cancer, but the exact molecular mechanism underlying HMGB1-mediated autophagy in NB has not been clearly defined. In the present study, we investigated the role of HMGB1 in the development of resistance to anticancer agents in NB. Anticancer agents including doxorubicin, cisplatin and etoposide each induced HMGB1 upregulation, promoted cytosolic HMGB1 translocation and the elevation of autophagic activity in human NB cells. RNA interference-mediated knockdown of HMGB1 restored the chemosensitivity of NB cells. Furthermore, mechanistic investigation revealed that HMGB1 promoted the proliferative activity and invasive potential of NB cells. HMGB1 enhanced drug resistance by inducing Beclin-1-mediated autophagy, an intracellular self-defense mechanism known to confer drug resistance. In addition, we found that HMGB1 facilitated autophagic progression and reduced oxidative stress induced by doxorubicin. Therefore, through its role as a regulator of autophagy, HMGB1 is a critical factor in the development of chemoresistance and tumorigenesis, and it may be a novel target for improving the efficacy of NB therapy.

The performance of dried blood spots (DBS) polymerase chain reaction (PCR) assays in screening for congenital cytomegalovirus (cCMV) infection varies between different studies. To determine whether the DBS PCR assay has sufficient accuracy to be used as a screening test for cCMV infection, we performed a meta-analysis of 15 studies (n = 26007 neonates) that evaluated the performance of DBS PCR tests in screening for cCMV infection and that met our inclusion criteria. The pooled sensitivity and specificity were 0.844 (95% CI = 0.812-0.872) and 0.999 (95% CI = 0.998-0.999), respectively, and the diagnostic odds ratio was 1362.10 (95%CI = 566.91-3272.60). As sensitivity analysis showed that the results were robust. In conclusion, the performance of DBS PCR assays for testing cCMV was more suitable for retrospective diagnosis than screening.

Objective: To explore the roles of ribavirin aerosol in the prevention and treatment of hand-foot-mouth disease (HFMD)., Methods: For this prospective, multicenter, randomized, double-blind and placebo-controlled trial, a total of 300 HFMD outpatients from 3 class 3A hospitals from July 2011 to June 2013 were divided into treatment (ribavirin aerosol) and control (placebo) groups (n = 150 each). The age range was 6 months to 6 years. The proportion of male and female was 1.5: 1. Temperature, herpes of mouth and skin rash were observed before and after treatments. Before treatment and 6-7 days after, their specimens of throat swab were collected and the levels of EV71 and CA16 detected with reverse transcription (RT)-PCR. The software SAS 9.2 was used for statistic data analyses., Results: Before treatment, no significant statistical difference existed in parameters between treatment and control groups (all P > 0.05). After treatment, the degree of herpes of mouth and papulovesicle of skin in treatment group was better than that in control group (100.0% (147/147) vs 83.9% (120/143), χ(2) = 109.21, P < 0.01); (100.0% (147/147) vs 95.9% (139/145) , χ(2) = 6.38, P < 0.05) . The virus negative conversion rates had significant inter-group difference (80.0% (102/110) vs 41.8% (41/98) , χ(2) = 37.06, P < 0.01). The temperature, compliance and differences were not significant (all P > 0.05). The effective rate of comprehensive efficacy in treatment group was higher than that in control group (93.9% (122/130) vs 52.0% (64/123), χ(2) = 111.08, P < 0.01). No obvious adverse drug reaction was observed., Conclusions: Ribavirin aerosol has multiple advantages of lower dose, quicker onset, higher local concentration, better clinical efficacy and fewer side-effects. Its therapeutic effect for local lesion is better than that for systemic lesion. Thus it may shorten the duration of oropharyngeal and skin lesions and lower the number and time of viral release.

Objective: To study the technological parameters of the enrichment purification of Cornus officinalis glycosides (COG) with macroporous resin and active carbon., Methods: COG was isolated and purified by active carbon and macroporous resin HPD100. The enrichment of COG was evaluated by HPLC method., Results: The optimum process was that 10 ml extract of Fructus Corni was absorbed with columns of macroporous resin and active carbon(R25 mm x H300 mm) and the columns were washed with 600 ml distilled water, then the morroniside and loganin was eluted from the macroporous resin and active carbon with ethanol., Conclusion: The elutive rate of morroniside and logann was about 85% by the macroporous resin, 96% by the active carbon. So this method enriching COG from Fructus Corni is practical.