Cuproptosis associated cytoskeletal destruction contributes to podocyte injury in chronic kidney disease.

The podocyte cytoskeleton determines the stability of podocyte structure and function, and their imbalance plays a pathogenic role in podocyte diseases. However, the underlying mechanism of podocyte cytoskeleton damage is not fully understood. Here, we investigate the specific role of cuproptosis in inducing podocyte cytoskeleton injury. In vitro and in vivo studies, exposure to high levels of copper and adriamycin (ADR) caused significant increases in copper concentration in intracellular and renal tissue. Moreover, excessive accumulation of copper induced cuproptosis, resulting in the destruction of the podocyte cytoskeleton. However, inhibition of copper accumulation to reduce cuproptosis also significantly alleviated the damage of podocyte cytoskeleton. In addition, inhibition of cuproptosis mitigated ADR-induced mitochondrial damage as well as the production of reactive oxygen species and depolarization of mitochondrial membrane potential, and restored ATP synthesis. Among the transcriptome sequencing data, the difference of CXCL5 was the most significant. Both high copper and ADR exposure can cause up-regulation of CXCL5, and CXCL5 deletion inhibits the occurrence of cuproptosis, thereby alleviating the podocyte cytoskeleton damage. This suggests that CXCL5 may act upstream of cuproptosis that mediates podocyte cytoskeleton damage. In conclusion, cuproptosis induced by excessive copper accumulation may induce podocyte cytoskeleton damage by promoting mitochondrial dysfunction, thereby causing podocyte injury. This indicates that cuproptosis plays an important role in the pathogenesis of podocyte injury and provides a basis for seeking potential targets for the treatment of chronic kidney disease.

miR-16-5p aggravates sepsis-associated acute kidney injury by inducing apoptosis.

Sepsis-associated acute kidney injury (S-AKI) is a common disease in pediatric intensive care units (ICU) with high morbidity and mortality. The newly discovered results indicate that microRNAs (miRNAs) play an important role in the diagnosis and treatment of S-AKI and can be used as markers for early diagnosis. In this study, the expression level of miR-16-5p was found to be significantly upregulated about 20-fold in S-AKI patients, and it also increased by 1.9 times in the renal tissue of S-AKI mice. Receiver operating characteristic (ROC) curve analysis showed that miR-16-5p had the highest predictive accuracy in the diagnosis of S-AKI (AUC = 0.9188). In vitro, the expression level of miR-16-5p in HK-2 cells treated with 10 µg/mL lipopolysaccharide (LPS) increased by more than 2 times. In addition, LPS-exposed renal tissue and HK-2 cells lead to upregulation of inflammatory cytokines IL-6, IL-1ß, TNF-a, and kidney damage molecules kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL). However, inhibition of miR-16-5p significantly mitigated LPS expose-mediated kidney injury and inflammation. Furthermore, LPS-exposed HK-2 cells increased more than 1.7-fold the expression levels of Bax and caspase-3, decreased 3.2-fold the expression level of B-cell lymphoma-2 (Bcl-2), and significantly promoted the occurrence of apoptosis. MiR-16-5p mimic further increased LPS-induced apoptosis in HK-2 cells. Nevertheless, inhibition of miR-16-5p significantly attenuated this effect. In summary, up-regulation of miR-16-5p expression can significantly aggravate renal injury and apoptosis in S-AKI, which also proves that miR-16-5p can be used as a potential biomarker to promote early identification of S-AKI.

Current status and continuing medical education need for general practitioners in Tibet, China: a cross-sectional study.

BACKGROUND: The Tibetan area is one of China's minority regions with a shortage of general practice personnel, which requires further training and staffing. This research helps to understand the current condition and demand for general practitioner (GP) training in Tibetan areas and to provide a reference for promoting GP education and training. METHODS: We conducted a cross-sectional survey using stratified sampling targeting 854 GPs in seven cities within the Tibetan Autonomous Region, utilizing an online questionnaire. Achieving a high response rate of 95.1%, 812 GPs provided invaluable insights. Our meticulously developed self-designed questionnaire, available in both Chinese and Tibetan versions, aimed to capture a wide array of data encompassing basic demographics, clinical skills, and specific training needs of GPs in the Tibetan areas. Prior to deployment, the questionnaire underwent rigorous development and refinement processes, including expert consultation and pilot testing, to ensure its content validity and reliability. In our analysis, we employed descriptive statistics to present the characteristics and current training needs of GPs in the Tibetan areas. Additionally, chi-square tests were utilized to examine discrepancies in training needs across various demographic groups, such as age, job positions, and educational backgrounds of the participating GPs. RESULTS: The study was completed by 812 (812/854, 95.1%) GPs, of whom 62.4% (507/812) were female. The top three training needs were hypertension (81.4%, 661/812), pregnancy management (80.7%, 655/812), and treatment of related patient conditions and events (80.5%, 654/812). Further research shows that the training required by GPs of different ages in "puncturing, catheterization, and indwelling gastric tube use" (64.6% vs. 54.8%, p = 9.5 × 10- 6) varies statistically. GPs in various positions have different training needs in "community-based chronic disease prevention and management" (76.6% vs. 63.9%, p = 0.009). The training needs of GPs with different educational backgrounds in "debridement, suturing, and fracture fixation" (65.6% vs. 73.2%, p = 0.027) were also statistically significant. CONCLUSIONS: This study suggests the need for targeted continuing medical education activities and for updating training topics and content. Course developers must consider the needs of GPs, as well as the age, job positions, and educational backgrounds of GPs practicing in the Tibetan Plateau region. TRIAL REGISTRATION: Not applicable.

Impact of health literacy and social support on medication adherence in patients with hypertension: a cross-sectional community-based study.

BACKGROUND: Previous studies have examined the associations of health literacy and social support with medication adherence among patients with hypertension. However, limited evidence exists regarding the mechanisms underlying the relationship between these factors and medication adherence. PURPOSE: To explore the prevalence of medication adherence and its determinants in patients with hypertension in Shanghai. METHODS: A community-based cross-sectional study was conducted among 1697 participants with hypertension. We collected sociodemographic and clinical characteristics as well as data regarding health literacy, social support, and medication adherence using questionnaires. We examined interactions among the factors using a structural equation model. RESULTS: The participants included 654 (38.54%) patients with a low degree of medication adherence and 1043 (61.46%) patients with a medium/high degree of adherence. Social support directly influenced adherence (ß = 0.165, P < 0.001) and indirectly influenced adherence through health literacy (ß = 0.087, P < 0.001). Health literacy directly influenced adherence (ß = 0.291, P < 0.001). Education indirectly affected adherence through both social support (ß = 0.048, P < 0.001) and health literacy (ß = 0.080, P < 0.001). Moreover, there was a sequential mediating effect of social support and health literacy on the association between education and adherence (ß = 0.025, P < 0.001). After controlling for age and marital status, similar results were also obtained, indicating a good model fit. CONCLUSIONS: The degree of medication adherence among hypertensive patients needs to improve. Health literacy and social support had both direct and indirect effects on adherence, and thus, these factors should be considered as tools to improve adherence.

[Development of General Practice in Communities From the Perspective of Supply and Demand].

Objective To put forward suggestions for improving the scheme of general practice for functional communities from the perspective of supply and demand,guide the efficient use of the resources of general practice by the communities,and incorporate the general practice of communities into hierarchical diagnosis and treatment management. Methods In July 2021,stratified random sampling was employed to conduct the questionnaire surveys of the young and middle-aged (demand side) and the general practitioners (supply side),respectively.SPSS 20.0 was used for data analysis. Results The two sides had the same cognition about the main reasons for not signing a contract with a family doctor,which were the lack of knowledge about general practitioners and the lack of face-to-face communication opportunities.They had the same response about the form of services,with high acceptance of medical services via WeChat,outpatient consultation,and the internet.There were differences in service content between the two sides.The top three demands of the young and middle-aged were appointment registration and referral in superior hospitals,medication guidance,and massage,acupuncture,and moxibustion.The top service self-rated by general practitioners was personalized guidance and report interpretation of physical examination,and the bottom was massage,acupuncture,and moxibustion. Conclusions The general practice varies between the demand and supply sides.General practitioners should be encouraged to enter and learn functional communities and provide personalized services,thus improving the general medical service in functional communities.

Pediatric Reference Change Value Optimized for Acute Kidney Injury: Multicenter Retrospective Study in China.

OBJECTIVES: The standard definition of pediatric acute kidney injury (AKI) is evolving, especially for critically ill in the PICU. We sought to validate the application of the Pediatric Reference Change Value Optimized for Acute Kidney Injury in Children (pROCK) criteria in critically ill children. DESIGN: Multicenter retrospective study. SETTING: Six PICUs in mainland China. PATIENTS: One thousand six hundred seventy-eight hospitalized children admitted to the PICU with at least two creatinine values within 7 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: AKI was diagnosed and staged according to the Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease (pRIFLE), the Kidney Disease Improving Global Outcomes (KDIGO), and the pROCK criteria. Multiple clinical parameters were assessed and analyzed along with 90-day follow-up outcomes. According to the definitions of pRIFLE, KDIGO, and pROCK, the prevalence of AKI in our cohort of 1,678 cases was 52.8% (886), 39.0% (655), and 19.0% (318), respectively. The presence of AKI, as defined by pROCK, was associated with increased number of injured organs, occurrence of sepsis, use of mechanical ventilation, use of continuous renal replace therapy ( p < 0.05), higher Pediatric Risk of Mortality III score, and higher Pediatric Logistic Organ Dysfunction-2 score ( p < 0.001). The survival curve of 90-day outcomes showed that pROCK was associated with shorter survival time (LogRank p < 0.001), and pROCK definition was associated with better separation of the different stages of AKI from non-AKI ( p < 0.001). CONCLUSIONS: In this retrospective analysis of AKI criteria in PICU admissions in China, pROCK is better correlated with severity and outcome of AKI. Hence, the pROCK criteria for AKI may have better utility in critically ill children.

LIM-Nebulette Reinforces Podocyte Structural Integrity by Linking Actin and Vimentin Filaments.

BACKGROUND: Maintenance of the intricate interdigitating morphology of podocytes is crucial for glomerular filtration. One of the key aspects of specialized podocyte morphology is the segregation and organization of distinct cytoskeletal filaments into different subcellular components, for which the exact mechanisms remain poorly understood. METHODS: Cells from rats, mice, and humans were used to describe the cytoskeletal configuration underlying podocyte structure. Screening the time-dependent proteomic changes in the rat puromycin aminonucleoside-induced nephropathy model correlated the actin-binding protein LIM-nebulette strongly with glomerular function. Single-cell RNA sequencing and immunogold labeling were used to determine Nebl expression specificity in podocytes. Automated high-content imaging, super-resolution microscopy, atomic force microscopy (AFM), live-cell imaging of calcium, and measurement of motility and adhesion dynamics characterized the physiologic role of LIM-nebulette in podocytes. RESULTS: Nebl knockout mice have increased susceptibility to adriamycin-induced nephropathy and display morphologic, cytoskeletal, and focal adhesion abnormalities with altered calcium dynamics, motility, and Rho GTPase activity. LIM-nebulette expression is decreased in diabetic nephropathy and FSGS patients at both the transcript and protein level. In mice, rats, and humans, LIM-nebulette expression is localized to primary, secondary, and tertiary processes of podocytes, where it colocalizes with focal adhesions as well as with vimentin fibers. LIM-nebulette shRNA knockdown in immortalized human podocytes leads to dysregulation of vimentin filament organization and reduced cellular elasticity as measured by AFM indentation. CONCLUSIONS: LIM-nebulette is a multifunctional cytoskeletal protein that is critical in the maintenance of podocyte structural integrity through active reorganization of focal adhesions, the actin cytoskeleton, and intermediate filaments.

Atorvastatin Relieves Cognitive Disorder After Sepsis Through Reverting Inflammatory Cytokines, Oxidative Stress, and Neuronal Apoptosis in Hippocampus.

This present research work reports the possible effects and the underlying mechanism of atorvastatin on survival rate and cognitive disorders after sepsis. Sepsis is a life-threatening dysfunction that arises when the body's response to infection causes injury to its own tissues and organs. Diffuse sepsis was induced by cecal ligation and puncture surgery (CLP) in ICR mice. 0.2 mg/kg body weight of atorvastatin was administrated intraperitoneally at 12 h before surgery. The survival of mice was calculated 24 h, 48 h, 72 h, and 96 h after CLP surgery. Two weeks later, open-field test and Morris water maze test were conducted to evaluate the protective effect of atorvastatin. Inflammatory cytokines in plasma, oxidative stress parameters, number of astrocytes, and neuronal cell deaths in the CA3 region of the hippocampus were examined using enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. The results indicate that pretreatment with atorvastatin can increase survival percentage and improve cognitive function. Atorvastatin reversed all these alterations in parallel with a decrease in circulating levels of cytokines (IL-1ß, IL-4, IL-6, and TNF-α) in plasma, inhibited the activities of oxidative stress parameters (lower TBARS levels, ratio of GSH/GSSH, and activities of SOD and CAT), enhanced the activity of citrate synthase in brain, and reduced the number of astrocytes and neuronal cell deaths in CA3 region of hippocampus. Overall, our results indicated that atorvastatin exhibited protective effects on survival rate and cognitive disorders after sepsis by inhibiting the release of inflammatory cytokines, oxidative stress, and neuronal apoptosis in brain tissue.

The quality of primary care in community health centers: comparison among urban, suburban and rural users in Shanghai, China.

OBJECTIVE: Following World Health Organization's initiatives to advance primary care, China put forth forceful policies including the Personal Family Doctor Contract to ensure that every family sign up with a qualified doctor in a community health center (CHC) ever since its 2009 New Health Reform. We used the Johns Hopkins-designed Primary Care Assessment Tool (PCAT) to assess primary care quality experienced by the contracted residents and compare this across different socioeconomic regions. METHODS: Using a multistage sampling method, four CHCs each were randomly selected from urban, suburban and rural districts of Shanghai, a metropolitan with 24 million residents. ANOVA and Multivariate analyses were used to assess the association between location of CHC and the quality of primary care experience. FINDINGS: A total of 2404 CHC users completed our survey. Except for the domain of coordination (information systems), users from suburban CHCs reported best primary care experiences in all other domains, followed by users of rural CHCs. After controlling for covariates, suburban CHC users were more likely to report higher total PCAT scores (ß = 1.57, P <  0.001) compared with those from urban CHCs. CONCLUSION: That contracted residents from suburban CHCs reporting better primary care experience than those from urban CHCs demonstrates the unique value of CHCs in relatively medical-underserved areas. In particular, urban CHCs could further strengthen first contact (utilization), first contact (accessibility), coordination (referral system), comprehensiveness (available), and community orientation aspects of primary care performance. However, all CHCs could improve coordination (information system).

Rotenone Protects Against Acetaminophen-Induced Kidney Injury by Attenuating Oxidative Stress and Inflammation.

BACKGROUND/AIMS: In clinic, excessive acetaminophen (APAP) can cause kidney damage with uncertain mechanisms. Recently, accumulating evidence demonstrated a pathogenic role of mitochondrial dysfunction in the kidney injury. Thus, in this study, rotenone, a mitochondrial complex I inhibitor, was applied to the mice with APAP-induced acute kidney injury to evaluate the effect of mitochondrial complex I inhibition on APAP nephrotoxicity. METHODS: After 3 days of rotenone pretreatment, mice were administered with APAP (300mg/kg) by intraperitoneal injection for 24 h. Then the kidney injury, inflammation, and oxidative stress were evaluated. RESULTS: APAP significantly enhanced the BUN, serum creatine, and cystatin C levels in line with a moderate alteration of renal morphology. Strikingly, rotenone treatment normalized BUN, serum creatinine, and cystatin C levels, as well as the kidney morphology. Meanwhile, APAP enhanced tubular injury markers of NGAL and KIM-1 by 347- and 5-fold at mRNA levels, respectively. By Western blotting, we confirmed a 15-fold increment of NGAL in APAP-exposed kidneys. Importantly, rotenone treatment largely normalized NGAL and KIM-1 levels and attenuated inflammatory response in APAP-treated mice. Similarly, rotenone treatment enhanced the expressions of SOD1-3 compared with APAP group in line with a significant suppression of kidney MDA content. Finally, we observed that inhibition of mitochondrial complex III failed to protect against APAP-induced nephrotoxicity. CONCLUSION: Mitochondrial complex I inhibitor rotenone protected kidneys against APAP-induced injury possibly via the inhibition of mitochondrial oxidative stress and inflammation.

Oxymatrine attenuates brain hypoxic-ischemic injury from apoptosis and oxidative stress: role of p-Akt/GSK3ß/HO-1/Nrf-2 signaling pathway.

To investigate the potential neuroprotection of oxymatrine in hypoxic-ischemic injury in rat's brain and the associated underlying mechanisms, modified neurological severity scores (mNSS) for neurological functional deficits, 2,3,5-triphenyl-tetrazolium chloride (TTC) staining for infarct volume, TUNEL assay and flow cytometry analysis for apoptosis were assessed. The expressions of Akt, glycogen synthase kinase 3 beta (GSK3ß), phosphorylated Akt (p-Akt), phosphorylated GSK3ß (p-GSK3ß), nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1) were measured by western blot. Our results showed that infarct volume and the apoptosis of NeuN-positive cells were significantly reduced in rats that administrated oxymatrine, with a corresponding improvement in neurological function after H/I. Upregulated p-Akt, p-GSK3ß, Nrf-2 and HO-1 expressions were observed in response to oxymatrine treatment. Moreover, the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 counteracted the protective effect of oxymatrine, evidenced by western blot and histological outcomes. To conclude, our results suggested that oxymatrine could exert efficacious neuroprotective effect against H/I injury by inhibiting apoptosis and oxidative stress, which might be related to the activation of Akt and GSK3ß and modulation of Nrf-2/HO-1 signaling pathway.

[Effects of ω-3 polyunsaturated fatty acids on lymphocyte apoptosis rate in rats with sepsis].

OBJECTIVE: To investigate the effects of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) on the apoptosis of thymic and splenic lymphocytes in rats with sepsis. METHODS: A total of 80 female Sprague-Dawley rats aged 7-8 weeks were randomly divided into model group, conventional lipid emulsion group (0.1 g/kg daily), low-dose ω-3 PUFAs group (0.1 g/kg daily), middle-dose ω-3 PUFAs group (0.2 g/kg daily), and high-dose ω-3 PUFAs group (0.3 g/kg daily). Cecal ligation and puncture were used to establish a rat model of sepsis. The treatment groups were then given tail vein injection of lipid emulsion or glucose diluents of ω-3 PUFAs at different doses, and the model group was given glucose injection via the tail vein at the same dose. According to the time of sacrifice, each group was further divided into 24-hour and 72-hour subgroups, with 8 rats in each subgroup. Hematoxylin and eosin staining was used to observe the pathological changes in the thymus and spleen. TUNEL was used to measure the apoptosis rates of thymic and splenic lymphocytes. RESULTS: In the three ω-3 PUFAs groups, the rats had a complete thymic lobular structure and clear structures of the cortex and medulla. In the model and the conventional lipid emulsion groups, the boundaries of the cortex and medulla were unclear and the number of lymphocytes was significantly reduced. In the ω-3 PUFAs groups, the structure of the red and white pulp of the spleen was maintained with the presence of splenic follicles, while in the model and the conventional lipid emulsion groups, the structure of the red and white pulp of the spleen was disordered and splenic follicles were significantly reduced or disappeared. Compared with the model and the conventional lipid emulsion groups, the ω-3 PUFAs groups showed significant reductions in the apoptosis rates of thymic and splenic lymphocytes at 24 and 72 hours (P<0.01). Compared with the low-dose ω-3 PUFAs group, the high-dose ω-3 PUFAs group had significantly reduced apoptosis rates of splenic lymphocytes at 24 and 72 hours (P<0.05). CONCLUSIONS: ω-3 PUFAs can reduce the apoptosis of thymic and splenic lymphocytes in rats with sepsis in a dose-dependent manner.

Clinical observation of glucocorticoid therapy for critically ill patients with COVID-19 pneumonia.

OBJECTIVE: We aimed to investigate the clinical effects of intravenous glucocorticoid (GC) therapy for severe COVID-19 pneumonia. METHODS: Seventy-two patients hospitalized with severe COVID-19 pneumonia who were discharged or died between 5 January 2020 and 3 March 2020 at Huangshi Infectious Disease Hospital were included. Patients were divided into a treatment group (GC group) and non-treatment group (non-GC group) according to whether they had received GCs within 7 days of hospital admission. RESULTS: There was no significant difference between groups for Acute Physiology and Chronic Health Evaluation (APACHE) II score and 28-day survival rate. The rate of invasive mechanical ventilation was higher in the GC group than in the non-GC group. On day 7 after admission, the GC group had shorter fever duration and higher white blood cell count than the non-GC group. In subgroup analysis by age and severity, there was no significant difference in 28-day survival rate and other indicators. Compared with those in the non-GC group, patients in the GC group more frequently required admission to the intensive care unit. CONCLUSION: In the present study, we found no significant improvement in patients with severe COVID-19 pneumonia treated with GCs within 7 days of admission.

A Systematic Review of Linezolid Pharmacokinetics/Pharmacodynamics in Patients Undergoing Continuous Renal Replacement Therapy: Does One Size Fit All?

BACKGROUND: Selection of the optimal antimicrobial posology in critically ill patients remains a challenge, especially in patients with sepsis who undergo continuous renal replacement therapy (CRRT). This systematic review aimed to analyze factors that influence the extracorporeal removal of linezolid. METHODS: A comprehensive search was performed to identify studies published up to March 2022 in PubMed, MEDLINE and EMBASE databases. Studies involving adults receiving CRRT and treatment with linezolid were considered eligible if the CRRT setting and linezolid's pharmacokinetic parameters were clearly mentioned. RESULTS: Six out of 110 potentially relevant studies were included. A total of 101 treatments were identified among 97 enrolled patients. Our analysis showed that continuous veno-venous hemodiafiltration (CVVHDF) was the most frequential used modality (52 cases). Despite distribution volume, the clearance (CL) of linezolid in these studies had large variability. Extracorporeal linezolid removal may be markedly impacted by CRRT dose. There is significant between-subject variability in the probability of pharmacokinetics-pharmacodynamics (PK-PD) target attainment of patients treated with CRRT. CONCLUSION: Dose adjustment, shortening the dosing interval, and continuous infusion were proposed as regimen optimization. Therapeutic drug monitoring is recommended due to the high variability of linezolid exposure among patients with CRRT, specifically for those whose bodyweight is high, renal function is preserved, and the MIC of infection bacteria is above 2 µg/mL.

Erythropoietin attenuates 6-hydroxydopamine-induced apoptosis via glycogen synthase kinase 3ß-mediated mitochondrial translocation of Bax in PC12 cells.

The aim of this study was to determine the mechanism by which erythropoietin (EPO) suppressed 6-hydroxydopamine (6-OHDA)-induced apoptosis. Our results showed that 6-OHDA remarkably decreased phosphorylation of glycogen synthase kinase 3ß (GSK3ß) as well as enhanced the level of Bax in the mitochondria. Besides, 6-OHDA decreased the mitochondrial expression of Bcl-2 without altering the cytoplasmic expression of Bcl-2. In line with these results, 6-OHDA treatment enhanced the apoptosis and caspase 3 activity in PC12 cells. These findings indicated that mitochondrial dysfunction was involved in the neurotoxicity of 6-OHDA and GSK3ß might act upstream of Bax/Bcl-2 and the caspase 3 pathways in 6-OHDA-treated PC12 cells. Furthermore, EPO reduced 6-OHDA-induced growth inhibition. Western blot exhibited that GSK3ß inhibitor 4-benzyl-2-methyl-1, 2,4-thiadiazolidine-3, 5-dione (TDZD8) and EPO not only increased the phosphorylation of GSK3ß but also inhibited the mitochondrial translocation of Bax. In agreement with these results, EPO and TDZD8 obviously increased the mitochondrial expression of Bcl-2. Finally, TDZD-8 and EPO significantly suppressed the enhanced apoptosis and activity of caspase 3 induced by 6-OHDA. Taken together, GSK3ß-mediated mitochondrial cell death pathway is involved in the neuroprotective effect of EPO against 6-OHDA-induced apoptosis.

Impaired cytokine production and decreased TLR2-mediated signaling in mouse infant macrophages.

Infants are known to be more susceptible to pathogens. This might be due in part to the impaired function of macrophage. In the present study, we observed that macrophages from infant mice produced decreased levels of TNF-α and IL-6, but increased IL-10 after stimulation with toll-like receptor 2 (TLR2) agonist zymosan. Moreover, zymosan-stimulated activation of mitogen-activated protein kinase (MAPK) p38 and ERK1/2 was significantly reduced in mouse infant macrophages. These effects could be reversed by using MAPK modulators. The findings suggest that the impaired cytokine production and decreased TLR2-mediated signaling in infant macrophages may contribute to the susceptibility of infants to bacterial infection.

Comparison of clinical outcomes and risk factors for COVID-19 infection in cancer patients without anticancer treatment and noncancer patients.

Background: Previous studies have shown that cancer patients have higher rates of coronavirus disease 2019 (COVID-19) infection and mortality than noncancer patients. However, the differences between cancer patients undergoing regular follow-up without anticancer treatment and noncancer patients with COVID-19 have remained insufficiently investigated. Methods: A retrospective case-control study of 52 patients with COVID-19 infection was performed with a 1:3 matched proportion of cancer patients undergoing regular follow-up without anticancer treatment and noncancer patients. The demographic characteristics, clinical data, laboratory tests, treatment, and complications of patients were collected from medical records. Chi-square tests and univariate and multivariate regressions were performed to assess the differences between these two cohorts of COVID-19 patients with and without cancer and risk factors for severe events in COVID-19 patients. Results: Increased C-reactive protein (CRP) (>4 mg/L) (p = 0.015) and lactate dehydrogenase (LDH) (>243 IU/L) (p = 0.038) were identified as risk factors for severe events in all enrolled COVID-19 patients based on multivariate analysis, but cancer as a chronic disease (p = 1.000) was not identified as an independent risk factor for severe events in COVID-19 patients. Compared with noncancer patients, cancer patients had a significantly longer median hospitalization time (29 days vs. 19 days, p = 0.048) and a higher incidence of hypoalbuminemia complications (84.6 vs. 46.2%, p = 0.016). Conclusions: Increased CRP and LDH were risk factors for severe events in all enrolled COVID-19 patients, and an increased incidence of hypoalbuminemia complications and longer hospitalization were noted in COVID-19 cancer patients undergoing regular follow-up without anticancer treatment compared with noncancer patients.

Analysis of clinical characteristics of 66 pediatric patients with B.1.617.2 (Delta) variant of COVID-19.

BACKGROUND: The aim of this study was to analyze the clinical characteristics of 66 pediatric patients with B.1.617.2 (Delta) variant of coronavirus disease 2019 (COVID-19). METHODS: Sixty-six pediatric patients with B.1.617.2 (Delta) variant of COVID-19 admitted to the hospital from July to August 2021 were classified into mild (n = 41) and moderate groups (n = 25). Clinical characteristics, laboratory data and dynamic trends in different time periods were analyzed retrospectively. RESULTS: There were no statistically significant differences in age, gender ratios and clinical symptoms between the mild group and the moderate group. All the patients in the moderate group had clusters of onsets, and the incubation period was shorter than that of the mild group. Within 24 hours of admission, the levels of erythrocyte sedimentation rate, cardiac troponin I, D-dimer in the moderate group were higher than that in the mild group (P < 0.05). The titers of immunoglobulin (Ig) G and IgM antibodies gradually increased after disease onset. Thirty-five (53.03%) children were tested positive for antibodies in 4-12 days. IgG increased gradually, while IgM decreased obviously in about 15 days after disease onset. The cycle threshold values of open reading frame 1ab and nucleocapsid protein gene in the severe acute respiratory syndrome coronavirus 2 genomes increased gradually on the 3rd, 6th, 9th, and 12th days after disease onset, compared with those in day 0. CONCLUSIONS: The symptoms of children with B.1.617.2 (Delta) variant of COVID-19 were mild. The description and analysis of the clinical characteristics and laboratory data can help medical staff to evaluate the condition of children with COVID-19 and to accumulate more clinical experience.

Chest CT features of children infected by B.1.617.2 (Delta) variant of COVID-19.

BACKGROUND: This study aimed to explore the imaging characteristics, diversity and changing trend in CT scans of pediatric patients infected with Delta-variant strain by studying imaging features of children infected with Delta and comparing the results to those of children with original COVID-19. METHODS: A retrospective, comparative analysis of initial chest CT manifestations between 63 pediatric patients infected with Delta variant in 2021 and 23 pediatric patients with COVID-19 in 2020 was conducted. Corresponding imaging features were analyzed. In addition, the changing trend in imaging features of COVID-19 Delta-variant cases were explored by evaluating the initial and follow-up CT scans. RESULTS: Among 63 children with Delta-variant COVID-19 in 2021, 34 (53.9%) showed positive chest CT presentation; and their CT score (1.10 ± 1.41) was significantly lower than that in 2020 (2.56 ± 3.5) (P = 0.0073). Lesion distribution: lung lesions of Delta cases appear mainly in the lower lungs on both sides. Most children had single lobe involvement (18 cases, 52.9%), 14 (41.2%) in the right lung alone, and 14 (41.2%) in both lungs. A majority of Delta cases displayed initially ground glass (23 cases, 67.6%) and nodular shadows (13 cases, 38.2%) in the first CT scan, with few extrapulmonary manifestations. The 34 children with abnormal chest CT for the first time have a total of 92 chest CT examinations. These children showed a statistically significant difference between the 0-3 day group and the 4-7 day group (P = 0.0392) and a significant difference between the 4-7 day group and the more than 8 days group (P = 0.0003). CONCLUSIONS: The early manifestations of COVID-19 in children with abnormal imaging are mostly small subpleural nodular ground glass opacity. The changes on the Delta-variant COVID-19 chest CT were milder than the original strain. The lesions reached a peak on CT in 4-7 days and quickly improved and absorbed after a week. Dynamic CT re-examination can achieve a good prognosis.

Computational Systems Pharmacology, Molecular Docking and Experiments Reveal the Protective Mechanism of Li-Da-Qian Mixture in the Treatment of Glomerulonephritis.

BACKGROUND: Glomerulonephritis is a common urinary system disease among children. Growing evidence suggests that traditional Chinese medicine has potential in treating glomerulonephritis, such as Li-Da-Qian mixture. Although its anti-glomerulonephritis and alleviating hematuria effects have been reported, the exact mechanism of Li-Da-Qian mixture devoting to glomerulonephritis remains unexplored. It was necessary to explore the mechanism of Li-Da-Qian mixture against glomerulonephritis using modern technology, such as Chinese medicine database and molecular biological experiments. METHODS: Online databases were used to look up ingredients and predict targets of Li-Da-Qian mixture against glomerulonephritis. The intersecting targets of Li-Da-Qian mixture and glomerulonephritis were selected for enrichment analysis. Cytoscape software was applied to establish network and MCODE analysis. Molecular docking was used for the primary validation. Furthermore, we examined the function of the core compounds analyzed from Li-Da-Qian mixture to rescue LPS-induced inflammation in vivo and vitro. We also explored whether the core compounds can alleviate TGFß1-induced renal fibrosis in mouse proximal tubular cells. RESULTS: Network pharmacological analysis of Li-Da-Qian evaluated 20 active ingredients including baicalein, luteolin and quercetin. A total of 113 key targets were screened, including IL6, VEGFA, TP53, EGF, MMP2, etc, and they were enriched in AGE-RAGE signaling pathway in diabetic complications, TNF and IL-17 signaling pathways. Moreover, the core ingredients succeeded in binding to the main targets via molecular docking, further identifying the anti-glomerulonephritis effects and improvement of vascular injury. Western blotting and qPCR also suggested that baicalein and luteolin can improve inflammation and restore disturbance of mesangial cells or kidney induced by LPS. In addition, baicalein and luteolin inhibited renal fibrosis in vitro.