Rational design of a lysosome-targeted fluorescent probe for monitoring the generation of hydroxyl radicals in ferroptosis pathways.

Ferroptosis is a newly discovered iron-dependent form of regulated cell death associated with high levels of hydroxyl radical (˙OH) production. Meanwhile, lysosome dysfunction has been shown to be one of the causes of ferroptosis. Although a variety of ˙OH-responsive fluorescent probes have been developed for detecting intracellular ˙OH in living cells, there are still only few lysosome-targeted probes to monitor the variation in lysosomal ˙OH levels during ferroptosis. Herein, we report a novel ˙OH-specific fluorescent probe HCy-Lyso, which is composed of the hydrocyanine and morpholine moiety. Upon treatment with ˙OH, its hydrocyanine unit was converted to the corresponding cyanine group, thus leading to a large π-conjugation extension of HCy-Lyso, accompanied by a significant fluorescence off-on response. Moreover, after reacting with ˙OH in an acidic environment, the protonation product of HCy-Lyso exhibits a higher fluorescence enhancement, which is suitable for detecting lysosomal ˙OH variation. HCy-Lyso has been utilized for imaging endogenous ˙OH in living cells under phorbol myristate acetate (PMA) stimuli and monitoring the changes in lysosomal ˙OH levels during ferroptosis. Thus, our study proposes a new strategy to design lysosome-targeted and ˙OH-responsive fluorescent probes to investigate the relationship between lysosomes and ferroptosis.

Seasonality of respiratory syncytial virus infection in children hospitalized with acute lower respiratory tract infections in Hunan, China, 2013-2022.

BACKGROUND: In China, respiratory syncytial virus (RSV) infections traditionally occur during the spring and winter seasons. However, a shift in the seasonal trend was noted in 2020-2022, during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This study investigated the seasonal characteristics of RSV infection in children hospitalized with acute lower respiratory tract infections (ALRTIs). The RSV epidemic season was defined as RSV positivity in > 10% of the hospitalized ALRTI cases each week. Nine RSV seasons were identified between 2013 and 2022, and nonlinear ordinary least squares regression models were used to assess the differences in year-to-year epidemic seasonality trends. RESULTS: We enrolled 49,658 hospitalized children diagnosed with ALRTIs over a 9-year period, and the RSV antigen-positive rate was 15.2% (n = 7,566/49,658). Between 2013 and 2022, the average onset and end of the RSV season occurred in week 44 (late October) and week 17 of the following year, respectively, with a typical duration of 27 weeks. However, at the onset of the COVID-19 pandemic, the usual spring RSV peak did not occur. Instead, the 2020 epidemic started in week 32, and RSV seasonality persisted into 2021, lasting for an unprecedented 87 weeks before concluding in March 2022. CONCLUSIONS: RSV seasonality was disrupted during the COVID-19 pandemic, and the season exhibited an unusually prolonged duration. These findings may provide valuable insights for clinical practice and public health considerations.

Multicenter study of seasonal and regional airborne allergens in Chinese preschoolers with allergic rhinitis.

This study is nationwide multicenter epidemiological research, aimed at investigating the distribution changes and seasonal patterns of various airborne allergens among preschool children with allergic rhinitis (AR) in different regions of China, and analyzing the clinical correlation between sensitization to various airborne allergens and AR symptoms in children. Information on children was collected through standard questionnaires, and total IgE (tIgE) and specific IgE (sIgE) for 11 inhalant allergens were tested. The results showed that dust mites are the primary allergens for preschool AR children (39%). Among pollen allergens, Amb a had the highest positivity rate (8.1%), followed by Art v (7.8%). The sensitization rates for two mites peaked in May (46.9% and 40.6%). Art v peaked in August (21.5%), while Amb a had peaks in May (12.7%) and August (17.8%). The sensitization peaks for various tree pollens mainly occurred in August. In the Eastern monsoon region, the sensitization rate to mites was significantly higher than in the Northwest arid and semi-arid regions; whereas, for pollen allergens, the sensitization rates to Amb a, Pla a, Pin a, Pop d, and Bet v were significantly higher in the Northwest arid and semi-arid regions than in the Eastern monsoon region. The correlation among various tree pollens, specifically between Pla a, Pin r, Pop d, and Bet v was strong (0.63 ~ 0.79), with a cross-overlapping percentage of 53.9%. Children with multiple pollen sensitizations had higher cumulative nasal symptom scores than those negative for pollen (P < 0.01). Children with only pollen sensitization had higher cumulative rhinitis symptom scores than the all-negative group (P < 0.0001) and the mite-only sensitization group [P < 0.05], while the mite-only sensitization group also had higher scores than the all-negative group [P < 0.05], and the group sensitized to both pollen and mites had lower scores than the pollen-only group [P < 0.05]. This study indicates that sensitization to mites and grass pollens exhibits significant regional differences, with grass pollen allergies primarily occurring in autumn, sensitization to pollens in general exhibits a pronounced seasonal pattern. Moreover, pollen sensitization aggravates nasal and ocular symptoms in AR children.

MiR-150-5p contributes to unexplained recurrent spontaneous abortion by targeting VEGFA and downregulating the PI3K/AKT/mTOR signaling pathway.

PURPOSE: The purpose of this study is to investigate the function of miR-150-5p in URSA. METHOD: Twenty-six chorionic villous tissues were collected to examine the expression of miR-150-5p and VEGFA by using quantitative polymerase chain reaction (qPCR) and western blot assay, respectively. Transwell assay was conducted to assess the migration and invasion ability of trophoblast cells. The dual-luciferase reporter assay was applied to determine the relationship between miR-150-5p and VEGFA in vitro. Relevant signaling pathway protein expression level was measured via western blot assay. Signaling transduction inhibitor LY294002 was used to block PI3K/AKT/mTOR signaling pathway. Finally, in vivo the effect of miR-150-5p on embryonic absorption rate was evaluated in mice. RESULTS: Clinical samples revealed that miR-150-5p expression was significantly elevated in the villous tissues and serum of URSA patients. Moreover, the overexpressing of miR-150-5p could inhibit both HTR-8/SVneo cell and JAR cell migration, invasion, and restrained PI3K/AKT/mTOR signaling pathway by targeting VEGFA in vitro. This inhibitory effect of miR-150-5p could be reversed by overexpressing the gene of vascular epithelial growth factor A (VEGFA). In contrary, inhibition of miR-150-5p significantly enhanced migration, invasion ability of both HTR-8/SVneo and JAR cells, and also could stimulate PI3K/AKT/mTOR signaling pathway. This promoting effect of miR-150-5p could be ameliorated by LY294002 (PI3K inhibitor). Finally, after miR-150-5p overexpression in vivo, the embryo resorption rate in pregnant mice was increased significantly. CONCLUSIONS: Overall, these findings imply that miR-150-5p is among the key factors that regulate the pathogenesis of URSA.

Two new seco-abietane type diterpenoids from the leaves of Isodon serra.

Two new seco-abietane type diterpenoids, named as isodonserra acid A and B (1-2), along with six known compounds, angustanoic acid A (3), epipalustric acid (4), raserrane (5), 7-methoxy coumarin (6), umbelliferone (7), and (-)-loliolide (8), were obtained from the leaves of Isodon serra. The new structures of compounds 1 and 2 were elucidated by analysing their 1D NMR, 2D NMR and HR-ESI-MS spectra. Compounds 1-8 showed moderate hepatoprotective activity against APAP-induced HepG2 cell injury with a cell survival rate from 50.4% to 78.7% at a concentration of 10 µM (p < .001, bicyclol as the positive drug, 71.7%).

Efficacy and safety of anti-CD38 monoclonal antibodies in patients with relapsed/refractory multiple myeloma: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.

Objectives: The current study aims to evaluate the safety and efficacy of anti-CD38 monoclonal antibodies (mAbs) among patients with relapsed/refractory multiple myeloma (RRMM) through meta-analysis. Methods: As of June 2023, we searched PubMed, Web of Science, Embase and the Cochrane Library. Randomized controlled trials (RCTs) which compared the clinical outcomes of anti-CD38 mAbs plus immunomodulatory drugs (IMiDs) or proteasome inhibitors (PIs) plus dexamethasone and IMiDs (or PIs) and dexamethasone alone for RRMM patients were included. Efficacy outcomes were mainly evaluated with progression-free survival (PFS) and overall survival (OS). The safety was analyzed with hematologic and nonhematologic treatment-emergent adverse events (TEAEs). All results were pooled using hazard ratio (HR), relative risk (RR), and their 95% confidence interval (CI) and prediction interval (PI). Results: This meta-analysis included 11 RCTs in total. Compared with IMiDs (or PIs) and dexamethasone alone, anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone significantly prolonged PFS (HR: 0.552, 95% CI = 0.461 to 0.659, 95% PI = 0.318 to 0.957) and OS (HR: 0.737, 95% CI = 0.657 to 0.827, 95% PI = 0.626 to 0.868) in patients with RRMM. Additionally, RRMM patients receiving anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone achieved higher rates of overall response (RR: 1.281, 95% CI = 1.144 to 1.434, 95% PI = 0.883 to 1.859), complete response or better (RR: 2.602, 95% CI = 1.977 to 3.424, 95% PI = 1.203 to 5.628), very good partial response (VGPR) or better (RR: 1.886, 95% CI = 1.532 to 2.322, 95% PI = 0.953 to 3.731), and minimum residual disease (MRD)-negative (RR: 4.147, 95% CI = 2.588 to 6.644, 95% PI = 1.056 to 16.283) than those receiving IMiDs (or PIs) and dexamethasone alone. For TEAEs, the rates of hematologic and nonhematologic TEAEs, including thrombocytopenia, neutropenia, upper respiratory tract infection (URTI), pneumonia, bronchitis, dyspnea, diarrhea, pyrexia, back pain, arthralgia, fatigue, insomnia, and hypertension, were higher in the anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone group than in the IMiDs (or PIs) and dexamethasone group. Conclusion: Our study showed that anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone improved PFS and OS, and achieved higher rates of overall response, complete response or better, VGPR or better, and MRD-negative, as well as higher rates of thrombocytopenia, neutropenia, URTI, pneumonia, bronchitis, dyspnea, diarrhea, pyrexia, back pain, arthralgia, fatigue, insomnia, and hypertension in RRMM patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023431071.

Involvement of estrogen receptor activation in kaempferol-3-O-glucoside's protection against aging-related cognition impairment and microglial inflammation.

Estrogens have been demonstrated to inhibit age-related cognitive decline via binding to estrogen receptors (ERs). As a natural flavonoid component of Cuscuta Chinensis Lam., Kaempferol-3-O-glucoside (K-3-G) not only possesses anti-neuroinflammatory potential but also functions as an agonist for ERα and ERß. This study aimed to determine whether K-3-G improved cognition during the aging process, with an emphasis on its effect on microglial inflammation. In vivo, K-3-G (5 or 10 mg/kg/day) was orally given to the senescence-accelerated mouse prone 8 (SAMP8) mice from six to eight-month old. In addition to mitigating the memory and learning deficits of SAMP8 mice, K-3-G upregulated the expression of ERα and ERß in their hippocampal CA1 region, with the higher dose being more effective. Less Iba-1+ microglial cells presented in SAMP8 mice treated with K-3-G. The formation of NLR Family Pyrin Domain Containing 3 (NLRP3) complex, production of pro-inflammatory cytokines and oxidative stress-related markers, as well as expression of pro-apoptotic proteins were reduced by K-3-G. In vitro, BV2 microglial cells exposed to oligomeric amyloid beta (Aß)1-42 were treated with 100 µM K-3-G. K-3-G showed similar anti-inflammatory effects on BV2 cells as in vivo. K-3-G-induced alterations were partly diminished by fulvestrant, an ER antagonist. Moreover, dual-luciferase reporter system demonstrated that K-3-G induced ER expression by activating the transcription of estrogen-response elements (EREs). Collectively, these findings demonstrate that K-3-G may be a novel therapeutic agent for senescence-related cognitive impairment by inhibiting microglial inflammation through its action on ERs.

Impact of robotic and open surgery on patient wound complications in gastric cancer surgery: A meta-analysis.

This meta-analysis is intended to evaluate the effect of both robotic and open-cut operations on postoperative complications of stomach carcinoma. From the earliest date until June 2023, a full and systemic search has been carried out on four main databases with keywords extracted from 'Robot', 'Gastr' and 'Opene'. The ROBINS-I instrument has been applied to evaluate the risk of bias in nonrandomized controlled trials. In these 11 trials, a total of 16 095 patients had received surgical treatment for stomach cancer and all 11 trials were nonrandomized, controlled trials. Abdominal abscesses were reported in 5 trials, wound infections in 8 trials, haemorrhage in 7 trials, wound dehiscence in 2 trials and total postoperative complications in 4 trials. Meta-analyses revealed no statistically significantly different rates of postoperative abdominal abscesses among patients who had received robotic operations than in those who had received open surgical procedures (OR, 0.91; 95% CI, 0.25, 3.36; p = 0.89). The incidence of bleeding after surgery was not significantly different from that in both groups (OR, 1.37; 95% CI, 0.69, 2.75; p = 0.37). Similarly, there was no significant difference between the two groups (OR, 0.78; 95% CI, 0.52, 1.18; p = 0.24). No significant difference was found between the two groups (OR, 1. 28; 95% CI, 0.75, 2.21; p = 0.36). No significant difference was found between the two groups of patients who had received the robotic operation and those who had received the surgery after the operation (OR, 1.14; 95% CI, 0.78, 1.66; p = 0.49). Generally speaking, this meta-analysis suggests that the use of robotics does not result in a reduction in certain postsurgical complications, including wound infections and abdominal abscesses. Thus, the use of a microinvasive robot for stomach carcinoma operation might not be better than that performed on the surgical site after the operation. This is a valuable guide for the surgeon to select the operative method.

[The role of bronchoscopy in slide tracheoplasty in children]. / 支气管镜在儿童Slide气管成形术中的应用.

OBJECTIVES: To study the role of bronchoscopy in slide tracheoplasty. METHODS: A retrospective analysis was conducted on the diagnosis and treatment of four children with tracheal stenosis admitted to Hunan Provincial People's Hospital from 2017 to 2020. The role of bronchoscopy was summarized in the preoperative evaluation, intraoperative positioning and measurement, and postoperative wound evaluation and treatment during slide tracheoplasty. RESULTS: Bronchoscopy evaluation before slide tracheoplasty showed that 3 of the 4 children had complete trachea rings, 2 had pulmonary artery sling, and 2 had multiple stenosis. Slide tracheoplasty was performed in the hospital on 3 children, and the midpoint of the stenosis segment was judged under bronchoscopy, and the length of the stenosis segment was measured, which assisted in the resection of the stenosis segment of the trachea. The pathogens were identified by lavage after the surgery. One child who developed scar traction 9 months after slide tracheoplasty in another hospital was improved by interventional treatment under bronchoscopy. Mucosal changes were found under bronchoscopy in 2 children 4 days after surgery, and the treatment plan was adjusted. One month after surgery, 2 children had granulation hyperplasia, which was improved by cryotherapy under bronchoscopy. One child abandoned treatment due to anastomotic necrosis and died. Three survivors were followed up for over 6 months with good prognosis, but all had tracheobronchial malacia. CONCLUSIONS: Bronchoscopy can be used for the management of slide tracheoplasty in children with tracheal stenosis, which is helpful to postoperative rehabilitation and follow-up.

The Function and Mechanism of Long Non-Coding RNA RP11-23J9.4 in Thyroid Cancer.

INTRODUCTION: The objective of this research is to explore whether LncRNA RP11 23J9.4 can be used as a targeted marker for the treatment of thyroid cancer (TC), downregulation of LncRNA RP11 23J9.4 and X-ray radiation have synergistic inhibitory effect on TC. METHODS: The expression of LncRNA RP11 23J9.4 in papillary thyroid carcinoma (PTC) cell was downregulated by cell transfection, and its inhibitory effect on PTC cells was proved through proliferation, invasion experiment, apoptosis, and cell cycle analysis. The transfected cells were irradiated with 2 Gy X-ray. The above methods were also used to detect whether they had synergistic inhibitory effect on TC. The expression of Axin2 gene and protein were detected by real-time PCR, Western blotting, and immunohistochemistry. RESULTS: On the one hand, it is proved that downregulating the expression of LncRNA RP11 23J9.4 can inhibit the development of TC through Axin2. On the other hand, it is clear that downregulation of LncRNA RP11 23J9.4 and X-ray radiation have synergistic inhibitory effect on TC. CONCLUSIONS: LncRNA RP11 23J9.4 and X-ray have significant synergistic effect on TC. LncRNA RP11 23J9.4 can be used as a marker for TC targeted therapy.

The effect of 17ß-estradiol plus norethisterone acetate on blood pressure and inflammation markers: A meta-analysis of randomized controlled trials.

OBJECTIVE: Several randomized controlled trials (RCTs) have explored the impact of 17ß-estradiol plus norethisterone acetate administration on blood pressure and inflammation markers, however, their findings have often been contradictory. Thus, we conducted a systematic review and meta-analysis of RCTs to assess the effects of this drug combination on systolic blood pressure (SBP), diastolic blood pressure (DBP) and C-reactive protein (CRP) concentrations. METHODS: The Cochrane Library, PubMed/Medline, Scopus, and Google Scholar were searched to identify relevant published RCTs. The pooled mean change and standard deviation (SD) of the outcomes were calculated using the STATA software (version 14) for Statistical Computing. RESULTS: A total of 18 publications were included in the current meta-analysis. In total, there were 12 RCT arms on SBP, 12 RCT arms on DBP, and 6 RCT arms on CRP levels. The administration of 17ß-estradiol plus norethisterone acetate intake increased SBP (WMD: 3.48 mmHg, 95% CI: 0.73, 6.23, P = 0.013), particularly in subjects aged ≥ 60 years (WMD: 5.89 mmHg, 95% CI: 1.71, 10.07, P = 0.006) or with a body mass index (BMI) < 30 kg/m2 (WMD: 6.55 mmHg, 95% CI: 2.64, 10.46, P = 0.012), as well as in the RCTs which lasted ≥ 6 months (WMD: 6.47 mmHg, 95% CI: 3.03, 9.90, P < 0.001),when 17ß-estradiol dosages were ≥ 2 mg/day (WMD: 4.12 mmHg, 95% CI: 1.03, 7.22, P = 0.009; I2 = 99%, P < 0.001) and in RCTs conducted on healthy postmenopausal women (WMD: 4.22 mmHg, 95% CI: 0.43, 8.01, P = 0.02; I2 = 94%, P < 0.001). DBP decreased following this drug combination in the RCTs which lasted < 6 months (WMD: -1.42 mmHg, 95% CI: -2.27, -0.57, P = 0.001). CRP concentrations increased following the use of this drug combination (WMD: 1.01 mg/L, 95% CI: 0.62, 1.41, P < 0.001), especially in participants aged < 60 years (WMD: 1.22 mg/L, 95% CI: 0.77, 1.68, P < 0.001) or with a BMI < 30 kg/m2 (WMD: 0.97 mg/L, 95% CI: 0.67, 1.27, P < 0.001), as well as in RCTs with a duration of ≥ 6 months (WMD: 1.15 mg/L, 95% CI: 0.57, 1.73, P < 0.001), when 17ß-estradiol dosages were ≥ 2 mg/day (WMD: 0.97 mg/L, 95% CI: 0.67, 1.27, P < 0.001; I2 = 55%, P = 0.107) and in RCTs conducted on healthy postmenopausal women (WMD: 1.22 mg/L, 95% CI: 0.77, 1.68, P < 0.001; I2 = 90%, P < 0.001). CONCLUSION: The administration of 17ß-estradiol plus norethisterone acetate increases SBP and CRP concentrations and, when prescribed for less than 6 months, decreases DBP. However, despite being statistically significant, the impact of this drug combination on SBP and DBP is not clinically relevant as the variation in blood pressure values was low.

Long Noncoding RNAs in Ovarian Cancer-Functions and Clinical Applications.

Long noncoding RNAs (lncRNAs) are RNA molecules with a length of more than 200 nt that have been discovered in recent years. LncRNAs can participate in regulating gene expression and various biological activities through multiple pathways, such as at the epigenetic level, transcriptional level, and posttranscriptional level. In recent years, with the increasing understanding of lncRNAs, a large number of studies have shown that lncRNAs are closely related to ovarian cancer and participate in its occurrence and development, providing a new method to investigate ovarian cancer. In this review, we analyzed and summarized the relationship between various lncRNAs and ovarian cancer in terms of occurrence, development, and clinical significance, in order to provide a theoretical basis for basic research and clinical application of ovarian cancer.

Construction and analysis of a nomogram prediction model for post-infectious bronchiolitis obliterans in children with adenovirus pneumonia after invasive mechanical ventilation.

BACKGROUND: Post-infectious bronchiolitis obliterans (PIBO) is the most common sequelae in children with adenovirus pneumonia (ADVP). However, there are few studies on the risk factors for PIBO occurrence. This study aims to investigate the risk factors for PIBO in pediatric patients with severe ADVP, especially after invasive mechanical ventilation (IMV), as well as to build a nomogram prediction model. METHODS: The clinical data, laboratory and imaging features, and treatment of 863 children with ADVP under 3 years old who were admitted to our hospital from January to December 2019 were retrospectively analyzed. Among them, 66 children with severe ADVP received IMV treatment. The situation and the influencing factors of PIBO in children with severe ADVP were explored, and a nomogram prediction model was constructed. RESULTS: Among the 863 cases of ADVP, 46 cases (5.33%) developed PIBO. Duration of fever, IMV, complications, and neutrophil percentage were independent risk factors for PIBO in children with ADVP. Among the 66 patients with ADVP who underwent IMV, 33 patients (50.0%) developed PIBO. Gender, duration of fever, adenovirus (ADV) load, and mixed fungal coinfections were independent risk factors for PIBO. In the nomogram prediction model analysis, the area under the curve (AUC) was 0.857; in addition, Hosmer‒Lemeshow (H-L) detection reflected good alignment (χ2 = 68.75, P < 0.01). CONCLUSIONS: A nomogram prediction model, which can be utilized to predict PIBO occurrence in pediatric patients with ADVP after IMV at an early time period, was successfully built.

Magnoflorine improves cognitive deficits and pathology of Alzheimer's disease via inhibiting of JNK signaling pathway.

BACKGROUND: Cognitive deficit is the main clinical feature of Alzheimer's disease (AD), and the massive death of neuronal cells is the leading cause of cognitive deficits. So, there is an urgent clinical need to discover effective drugs to protect brain neurons from damage in order to treat AD. Naturally-derived compounds have always been an important source of new drug discovery because of their diverse pharmacological activities, reliable efficacy and low toxicity. Magnoflorine is a quaternary aporphine alkaloid, which naturally exist in some commonly used herbal medicines, and has good anti-inflammatory and antioxidant effects. However, magnoflorine has not been reported in AD. HYPOTHESIS/PURPOSE: To investigate the therapeutic effect and mechanism of magnoflorine on AD. METHODS: Neuronal damage was detected by flow cytometry, immunofluorescence and western blotting. Oxidative stress was measured by detection of SOD and MDA, as well as JC-1 and reactive oxygen species (ROS) staining. The APP/PS1 mice were given drugs by intraperitoneal injection (I.P.) every day for one month, and then the new object recognition and Morris water maze were used to detect the cognitive ability of the mice. RESULTS: We demonstrated that magnoflorine reduced Aß-induced PC12 cell apoptosis and intracellular ROS generation. Further studies found that magnoflorine significantly improved cognitive deficits and AD-type pathology. Most interestingly, the efficacy of magnoflorine was better than that of the clinical control drug donepezil. Mechanistically, based on RNA-sequencing analysis, we found that magnoflorine significantly inhibited phosphorylated c-Jun N-terminal kinase (JNK) in AD models. This result was further validated using a JNK inhibitor. CONCLUSION: Our results indicate that magnoflorine improves cognitive deficits and pathology of AD through inhibiting of JNK signaling pathway. Thus, magnoflorine may be a potential therapeutic candidate for AD.

A multicentre study on the incidence of respiratory viruses in children with community-acquired pneumonia requiring hospitalization in the setting of the zero-COVID policy in China.

BACKGROUND: Stringent nonpharmaceutical interventions (NPIs) have been implemented worldwide to combat the COVID-19 pandemic, and the circulation and seasonality of common respiratory viruses have subsequently changed. There have been few multicentre studies or comparisons of the prevalence of respiratory viruses accounting for community-acquired pneumonia (CAP) in hospitalized children between the pre-COVID period and the period after community and school reopening in the setting of the zero-COVID policy. METHODS: We included 1543 children with CAP who required hospitalization from November 1, 2020 to April 30, 2021 (period 1), and 629 children with the same conditions from November 1, 2018, to April 30, 2019 (period 2), in our study. All respiratory samples from these patients were screened for six respiratory viruses (respiratory syncytial virus [RSV], adenovirus [ADV], influenza A virus [Flu A], influenza B virus [Flu B], parainfluenza virus type 1 [PIV1], and parainfluenza virus type 3 [PIV3]) using a multiplex real-time PCR assay. RESULTS AND CONCLUSIONS: The median ages of the enrolled patients at the time of diagnosis were 1.5 years and 1.0 years for period 1 and period 2, respectively. In period 1, viral pathogens were detected in 50.3% (776/1543) of the enrolled patients. The most frequently identified viral pathogen was RSV (35.9%, 554/1543), followed by PIV3 (9.6%, 148/1543), PIV1 (3.6%, 56/1543), ADV (3.4%, 52/1543), Flu A (1.0%, 16/1543), and Flu B (0.8%, 13/1543). The total detection rates of these six viruses in the peak season of CAP were at the pre-COVID level. The prevalence of Flu A decreased dramatically, and circulation activity was low compared to pre-COVID levels, while the incidence of PIV3 increased significantly. There were no significant differences in the detection rates of RSV, ADV, Flu B, and PIV1 between the two periods. Our results showed that respiratory viruses accounted for CAP in hospitalized children at pre-COVID levels as communities and schools reopened within the zero-COVID policy, although the prevalence aetiology spectrum varied.

tBHQ attenuates podocyte injury in diabetic nephropathy by inhibiting NADPH oxidase-derived ROS generation via the Nrf2/HO-1 signalling pathway.

Aims: Oxidative stress plays a crucial role in podocyte injury in diabetic nephropathy (DN). tert-Butylhydroquinone (tBHQ) is an activator of Nrf2 that exerts protective effects in diabetic mice, but the underlying mechanism of tBHQ in the podocytes of DN is not fully understood. Materials and methods: A high glucose (HG)-induced HK2 cell model and streptozotocin-induced rat model of DN were established and treated with tBHQ or apocynin. The expression levels of Nrf2, HO-1, NOX2 and NOX4 were determined by Western blot or immunohistochemical staining. The level of oxidative stress in podocytes or kidney tissues was assessed using DCFH-DA or dihydroethidium (DHE) staining. Cell injury was assessed by F-actin staining and flow cytometry analysis. Key findings: We showed that HG treatment increased the expressions of NOX2 and NOX4 and enhanced ROS production in podocytes. Inhibition of NADPH oxidase activity by apocynin dramatically attenuated HG-induced ROS production and further alleviated cell injury and apoptosis in podocytes. Moreover, we found that HG inhibited the Nrf2/HO-1 signalling pathway in podocytes; however, tBHQ treatment significantly activated the Nrf2 signalling pathway, inhibited NADPH oxidase activity, and attenuated ROS production and cell injury in HG-treated podocytes. Furthermore, we observed that tBHQ treatment partially attenuated renal injury, activated the Nrf2 signalling pathway, inhibited NADPH oxidase activity and reduced ROS generation in the kidneys of STZ-induced diabetic rats. Significance: These results suggest that tBHQ exerts a protective role in hyperglycaemia-induced podocyte injury, and that the potential protective mechanism of tBHQ involves inhibiting NADPH oxidase-derived ROS generation by activating the Nrf2/HO-1 signalling pathway.

Astragalin alleviates cognitive deficits and neuronal damage in SAMP8 mice through upregulating estrogen receptor expression.

Senile plaques composed of ß-amyloid protein (Aß) and neurofibrillary tangles (NFTs) composed of intracellular hyper-phosphorylated tau are major causes of cognitive impairment and neuronal damage in Alzheimer disease (AD). Astragalin (AST), a naturally-occurring flavonoid compound, was reported to have neuroprotective effects in the brain, but its effects in AD remain unknown. Herein, the learning and memory deficits were alleviated and neuronal damage in the hippocampus were inhibited after the senescence-accelerated mouse prone 8 (SAMP8) mouse were given AST (5 mg/kg or 10 mg/kg) daily by gavage for 2 months. Furthermore, AST reduced Aß1-40 and Aß1-42 deposition, decreased ß-carboxyl-terminal fragment (ß-CTF) protein level and tau hyper-phosphorylation, but increased α-CTF protein level and glycogen synthase kinase-3beta (GSK-3ß) phosphorylation in hippocampus of SAMP8 mice. Meanwhile, the effects of AST on AD were also explored in vitro by treating primary neurons with amyloid-ß1-42 oligomers (Aß1-42O). Consistently, AST also alleviated amyloid-ß1-42 oligomers (Aß1-42O)-induced neuronal damage, amyloid plaques, and tau phosphorylation in vitro model. Of note, estrogen receptor (ER)α and ERß expression in the hippocampus of SAMP8 mice and Aß1-42O-treated neurons was significantly decreased but their levels were increased by AST. Moreover, in vivo and in vitro experiments revealed that ER antagonist, Fulvestrant, reversed the effects caused by AST. Altogether, our investigation indicates that AST may ameliorate cognitive deficits and AD-type pathologies in SAMP8 mice and Aß1-42O-treated neurons through upregulating ERα and ERß expression. Our findings indicate the value of AST as a potential reagent for AD treatment.

Predictive Value of Adenoviral Load for Bronchial Mucus Plugs Formation in Children with Adenovirus Pneumonia.

Background: The study aimed to explore risk factors for bronchial mucus plugs (BMP) formation in children with adenovirus (AdV) pneumonia. Methods: A retrospective study was conducted on children with AdV pneumonia who underwent bronchoscopy from January 2019 to December 2019. Children were divided into the BMP group and the control group, depending on whether BMP was formed or not. The clinical information and treatment proposals of the two groups of children were counted and analyzed via multiple logistic regression analysis, ROC curve analysis, and correlation analysis. Results: Among 453 patients with AdV pneumonia, 185 (40.84%) were in the BMP group. Among all the cases, there were 188 patients with a single AdV infection, including 64 (34.04%) in the BMP group and 124 (65.96%) in the control group. The incidence of dyspnea, poor spirits, mixed infections, and other symptoms in the BMP group was higher than in the control group. Children in the BMP group had a longer heat range. C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer (DD), and AdV load levels were higher in the MBP group. AdV load, Mycoplasma coinfection, DD, heat range, and LDH were independent risk factors for BMP, among which AdV load was the most significant (AUC = 0.819). AdV load was positively correlated with other risk factors, respectively. AdV load and heat range were independent risk factors for BMP patients with a single AdV infection. Conclusion: AdV load might have important clinical value in predicting BMP development in AdV pneumonia.