Febrile young infants and the association with enterovirus infection.

BACKGROUND: Enterovirus is a common pediatric infectious disease, but the epidemiological data in young infants were lacking. This study aims to evaluate the role of enterovirus in febrile young infants and identify risk factors for severe infections. METHODS: We enrolled febrile infants younger than 90 days admitted to National Taiwan University Hospital from January 2010 to June 2021. Enterovirus infection was confirmed via viral isolation or pan-enterovirus PCR. Central nervous system involvement was defined by positive culture or PCR in cerebrospinal fluid. Severe complications included sepsis, hepatic failure, myocarditis, shock, encephalitis, acute kidney injury, respiratory failure, and multiorgan failure. RESULTS: Out of 840 febrile infants, 17.4% (n = 146) had enterovirus infection. Among these, 46% (n = 67) presented with meningitis and/or encephalitis. Early-onset enterovirus infection within the first two weeks of life was significantly linked to increased risks of anemia (hemoglobin <9 g/dL), ICU admission, central nervous system involvement, shock, hepatic failure, and mortality. Multivariable logistic regression identified high-risk serotypes (aOR 17.4, [95% CI 1.58, 191.5], p = 0.019) and hemoglobin <9 g/dL (aOR 44.9, [95% CI 5.6, 357.6], p < 0.001) as significant risk factors for severe complications. CONCLUSIONS: Enterovirus accounted for 17.4% of the etiology in febrile young infants and the case-fatality rate was 2%. Febrile young infants who had risk factors of enterovirus infection should consider viral culture or PCR examination for confirmation.

Effect of moxibustion on ATP-sensitive potassium channel (KATP) of bladder in detrusor overactivity rats. / 隔姜隔盐灸"神阙"å¯¹é€¼å°¿è‚Œè¿‡åº¦æ´»åŠ¨å¤§é¼ è†€èƒ±ATP敏感性钾离子通道的影响.

OBJECTIVES: To observe the effect of ginger-salt-partitioned moxibustion on ATP-sensitive potassium (KATP) channel of bladder in detrusor overactivity (DO) rats. METHODS: Female SD rats were randomly divided into sham operation, model, moxibustion and antagonist groups (n=9 in each group). Thorax (T) 10 spinal cord transection was performed by surgery. Ginger-salt partitioned moxibustion was applied to "Shenque" (CV8) for 3 cones, once daily for 14 consecutive days. Rats of the antagonist group were intraperitoneally injected with KATP channel specific antagonist glibenclamide (10 µg·kg-1·d-1) once daily for 14 consecutive days. Urodynamic tests were performed after treatment. The distribution and expression of KATP channel tetrameric subunit (SUR2B) in the bladder of rats was observed by immunofluorescence. The protein and mRNA expression levels of SUR2B in bladder tissue were detected by Western blot and qPCR respectively. RESULTS: Compared with the sham operation group, rats of the model group showed intensive and large phasic contractions of the detrusor during bladder filling, the frequency and amplitude of phasic contractions of the detrusor 5 min before leakage were significantly increased (P<0.001)；the voiding threshold pressure was significantly decreased (P<0.001)；the bladder perfusion volume was increased (P<0.001)；the SUR2B protein and mRNA expression in bladder tissue were significantly reduced (P<0.001). Compared with the model group and the antagonist group, the above-mentioned indicators in the moxibustion group were all reversed (P<0.01, P<0.001, P<0.05). CONCLUSIONS: Ginger-salt partitioned moxibustion can reduce the frequency and amplitude of detrusor phase contraction during bladder filling and prolong the time of first phase contraction in DO rats, which may be associated with up-regulating the expression level of KATP channel protein and mRNA, promoting the outflow of potassium ions, and inhibiting the inflow of calcium ions, thus improve the stability of detrusor during storage.

The effect of nutritional risk management program on the growth and development of infants and toddlers with congenital heart disease after discharge.

Objective: To evaluate the effect of nutritional risk management program on the growth and development of infants and toddlers with congenital heart disease (CHD) after discharge. Methods: Infants and toddlers with CHD discharged from a children's specialized hospital in southeast China were selected as the research subjects. The subjects were divided into the intervention group and the control group. The intervention group underwent a nutritional risk management program combined with traditional follow-up after discharge, whereas the control group received traditional follow-up after discharge. The primary outcome measure were the height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), and weight-for-height Z-score (WHZ) at different time point and the percentage of growth and development curves were also recorded and analyzed. Results: There were no statistically significant differences in general characteristics between the two groups. However, in the intervention group, the percentages of HAZ < -2, WAZ < -2, and WHZ < -2 were lower than those in the control group at 3rd and 6th months after discharge (P < 0.05). The percentage of growth and development curves (3%-97%) was higher than that in the control group (P < 0.05). The readmission rate within 6 months after discharge in the intervention group was lower than that in the control group (P < 0.05). Conclusion: Implementing nutritional risk management program for infants and toddlers with CHD after discharge can help improve postoperative malnutrition, promote growth and development and achieve catch-up growth as soon as possible.

Downregulation of autophagy is associated with poor clinical outcome after immunochemotherapy in patients with diffuse large B-cell lymphoma.

This study aimed to determine the expression levels of the autophagy markers Beclin-1 and p62 in patients with diffuse large B-cell lymphoma (DLBCL) and explore the association between autophagy and disease prognosis. The expression of Beclin-1 and p62 was investigated in patients with DLBCL and patients with reactive lymphoproliferative disease (RLD) using immunohistochemistry. The association between the clinical characteristics of patients with DLBCL and autophagy status was further analyzed. Beclin-1 levels were increased in RLD patients compared with those with DLBCL, but the difference was not statistically significant (p > 0.05). p62 levels in DLBCL patients were significantly higher than those in RLD patients (p < 0.05). Beclin-1 expression was associated only with the Ann Arbor stage (p < 0.05), whereas p62 expression was associated with the Ann Arbor stage, IPI score, extranodal involvement, and Ki-67 index (p < 0.05). Beclin-1 and p62 levels were not associated with short-term treatment efficacy in DLBCL patients. Survival analysis showed that Beclin-1 expression had no significant effect on 2-year progression-free survival (PFS) or overall survival (OS) (p > 0.05). However, high p62 expression in DLBCL patients was associated with reduced 2-year PFS compared with that of patients with low p62 expression (p < 0.05); the 2-year OS was not affected (p > 0.05). Our results demonstrate that autophagic activity affects the prognosis of DLBCL patients; the lower the autophagic activity, the shorter the PFS. Targeted p62 knockout may be a novel therapeutic strategy for the treatment of DLBCL patients.

[Distribution Characteristics of Soil Aggregate Stability and Organic Carbon of Different Grassland Types in the Temperate Desert of Longzhong Loess Plateau].

Soil aggregate stability and organic carbon （SOC） are important indicators of soil structure and quality and play a key role in the improvement of soil quality in temperate deserts. This study aimed to investigate the distribution patterns, stability of soil aggregates, and variation characteristics of the content of aggregate organic carbon in different grassland types in temperate deserts and their interrelationships. Four grassland types in a temperate desert （Kalidium foliatum type, Reaumuria songarica type, Salsola passerina type, and Sympegma regelii type） in the Longzhong Loess Plateau as research objects, and the soil aggregate particle size distribution characteristics were determined using the wet sieving method. The stability of soil aggregates was analyzed by calculating aggregate stability indicators and the contribution of aggregate particle size SOC to bulk soil SOC content. Correlation analysis, principal component analysis, and linear fitting equations were used to reveal the relationship between the soil aggregate content and aggregate particle size SOC and aggregate stability. The results showed that the content of >0.25 mm aggregates （R0.25）, mean weight diameter （MWD）, geometric mean diameter （GMD）, and bulk soil SOC content in each soil layer （0-10, 10-20, and 20-30 cm） of the K. foliatum type grassland were significantly higher than that of the R. songarica type and S. regelii type （P<0.05）. The SOC content of 0.053-0.25 mm and <0.053 mm particle size in each soil layer of the K. foliatum type grassland were significantly higher than that of the S. regelii type （P<0.05）. Surface and subsurface soils （0-10 cm and 10-20 cm） had the significantly highest contribution of 0.25-2 mm particle size SOC to the bulk soil SOC content （P<0.05）. Additionally, as the soil layer deepened, the R0.25, MWD, GMD, bulk soil, and aggregate SOC contents of the K. foliatum type grassland showed a tendency to increase first and then decrease, with the highest contents from 10-20 cm. Kalidium foliatum type grassland aggregate content was dominated by 0.25-2 mm aggregates, whereas the other three grassland types were dominated by 0.053-0.25 mm aggregates. In addition, bulk soil SOC content was significantly correlated with R0.25, MWD, GMD, and ELT （P<0.01）, and the 0.25 mm aggregate was the critical size of positive and negative correlation. R0.25, MWD, GMD, and ELT values were the key factors influencing bulk soil SOC in grassland. The equation fitted to bulk soil SOC content, and GMD was the most suitable to describe the relationship between SOC content and the stability of soil aggregates. Therefore, compared with other grassland types, K. foliatum type grassland had a promoting effect on the soil aggregate stability and the improvement of soil quality.

[Mechanism of Panax notoginseng saponins in treating diabetic kidney disease based on network pharmacology and experimental verification].

This study aims to investigate the therapeutic effect and mechanism of Panax notoginseng saponins(PNS) on diabetic kidney disease(DKD) based on network pharmacology, molecular docking, animal experiments. Network pharmacology was employed to screen the potential targets, and STRING was employed to build the protein-protein interaction network. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out for the core targets screened out, and a ″components-targets-pathways″ visualization network was constructed to predict the potential mechanism of PNS in treating DKD. Five active ingredients were screened from PNS, the core targets of which for treating DKD were AKT1, STAT3, ESR1, HSP90AA1, MTOR, et al. The KEGG enrichment analysis showed that the pathways related to PNS for treating DKD included the pathway in cancer, chemical carcinogenesis-receptor activation, and PI3K-AKT signaling pathway. GO analysis revealed that protein binding, homologous protein binding, enzyme binding, and ATP binding were the main biological processes involved in the treatment of DKD with PNS. Male 6-week-old db/db mice were randomized into model, dapagliflozin, and low-dose and high-dose PNS groups, with 10 mice in each group. Ten 6-week-old db/m mice were used as the control group. Mice were administrated with corresponding drugs or distilled water(control and model groups) by gavage once a day for 8 weeks. The body weight, fasting blood glucose, kidney index, microalbuminuria, creatinine, microalbuminuria/creatinine ratio, and urea nitrogen content in the urine of mice were determined. Hematoxylin-eosin(HE) staining, periodic acid-Schiff(PAS) staining, and Masson staining were performed to observe the protective effect of PNS on the renal tissues in db/db mice. The results showed that PNS could significantly reduce the fasting blood glucose level and improve the renal damage in db/db mice. Western blot results showed that PNS down-regulated the protein levels of p-AKT1 and p-STAT3 and decreased the p-AKT1/AKT1 and p-STAT3/STAT3 ratios. In addition, high-dose PNS down-regulated the protein level of PIK3CA. In conclusion, PNS may exert the kidney-protecting effects in DKD by inhibiting STAT3 via the PI3K-AKT signaling pathway.

Development of a Dementia Case Management Information System App: Mixed Methods Study.

BACKGROUND: Case managers for persons with dementia not only coordinate patient care but also provide family caregivers with educational material and available support services. Taiwan uses a government-based information system for monitoring the provision of health care services. Unfortunately, scheduling patient care and providing information to family caregivers continues to be paper-based, which results in a duplication of patient assessments, complicates scheduling of follow-ups, and hinders communication with caregivers, which limits the ability of case managers to provide cohesive, quality care. OBJECTIVE: This multiphase study aimed to develop an electronic information system for dementia care case managers based on their perceived case management needs and what they would like included in an electronic health care app. METHODS: Case managers were recruited to participate (N=63) by purposive sampling from 28 facilities representing two types of community-based dementia care centers in Taiwan. A dementia case management information system (DCMIS) app was developed in four phases. Phase 1 assessed what should be included in the app by analyzing qualitative face-to-face or internet-based interviews with 33 case managers. Phase 2 formulated a framework for the app to support case managers based on key categories identified in phase 1. During phase 3, a multidisciplinary team of information technology engineers and dementia care experts developed the DCMIS app: hardware and software components were selected, including platforms for messaging, data management, and security. The app was designed to eventually interface with a family caregiver app. Phase 4 involved pilot-testing the DCMIS app with a second group of managers (n=30); feedback was provided via face-to-face interviews about their user experience. RESULTS: Findings from interviews in phase 1 indicated the DCMIS framework should include unified databases for patient reminder follow-up scheduling, support services, a health education module, and shared recordkeeping to facilitate teamwork, networking, and communication. The DCMIS app was built on the LINE (LY Corporation) messaging platform, which is the mobile app most widely used in Taiwan. An open-source database management system allows secure entry and storage of user information and patient data. Case managers had easy access to educational materials on dementia and caregiving for persons living with dementia that could be provided to caregivers. Interviews with case managers following pilot testing indicated that the DCMIS app facilitated the completion of tasks and management responsibilities. Some case managers thought it would be helpful to have a DCMIS desktop computer system rather than a mobile app. CONCLUSIONS: Based on pilot testing, the DCMIS app could reduce the growing challenges of high caseloads faced by case managers of persons with dementia, which could improve continuity of care. These findings will serve as a reference when the system is fully developed and integrated with the electronic health care system in Taiwan.

Response of soil-microbe-extracellular enzyme stoichiometric characteristics to nitrogen deposition in a Pinus yunnanensis forest in central Yunnan Province, Southwest China.

To understand the effects of nitrogen deposition on element cycling and nutrient limitation status in forest ecosystems, we examined the effects of nitrogen deposition on the stoichiometric characteristics of forest soil-microbial-extracellular enzymes in Pinus yunnanensis forest. We conducted a field experiment with control (CK, 0 g N·m-2·a-1), low nitrogen (LN, 10 g N·m-2·a-1), medium nitrogen (MN, 20 g N·m-2·a-1) and high nitrogen (HN, 25 g N·m-2·a-1) since 2019. We collected soil samples (0-5 cm, 5-10 cm and 10-20 cm) at September 2022, and measured the contents of soil organic, total nitrogen, total phosphorus, microbial biomass carbon, nitrogen and phosphorus (MBC, MBN, MBP) and the activities of C, N, and P acquisition enzymes. The results showed that nitrogen deposition significantly reduced soil organic content, C:N and C:P by 6.9%-29.8%, 7.6%-45.2% and 6.5%-28.6%, and increased soil total N content and N:P by 10.0%-45.0% and 19.0%-46.0%, respectively. Nitrogen addition did not affect soil total P content. Except for soil C:N and C:P, soil nutrient content and stoichiometric ratio were highest in 0-5 cm soil layer. MN and HN treatments significantly decreased MBN by 11.0%-12.7%. MBC, MBP, and their stoichiometry did not change significantly under nitrogen deposition. Soil microbial nutrient content in 0-5 cm soil layer was significantly higher than that in other soil layers. Nitrogen deposition significantly decreased the activities of cellobiose hydrolase and leucine aminopeptidase (decreased by 14.5%-16.2% and 48.7%-66.3%). HN treatment promoted ß-1,4-glucosidase activity (increased by 68.0%), but inhibited soil enzyme stoichiometric carbon to nitrogen ratio and nitrogen to phosphorus ratio (decreased by 95.4% and 88.4%). LN and MN treatment promoted ß-1,4-N-acetylglucosaminidase activity (increased by 68.3%-116.6%), but inhibited enzyme stoichiometric carbon to phosphorus ratio (decreased by 14.9%-29.4%). Alkaline phosphatase activity had no significant change. Soil enzyme activities were significantly decreased with increasing soil depth. Soil total N and total P and microbial nutrients were negatively correlated with vector angle (representing microbial nitrogen or phosphorus limitation), while vector length (representing microbial carbon limitation) was consistently significantly positively correlated with vector angle, suggesting the synergistic promotion between microbial carbon limitation and phosphorus limitation. Nitrogen deposition gradually shifted to phosphorus limitation while alleviating microbial nitrogen limitation in P. yunnanensis forest. In addition, microbial activities in this region was limited by C availability, and the relationship between microbial C and P limitation was proportional.

Selection of dialysis methods for end-stage kidney disease patients with diabetes.

The increasing prevalence of diabetes has led to a growing population of end-stage kidney disease (ESKD) patients with diabetes. Currently, kidney transplantation is the best treatment option for ESKD patients; however, it is limited by the lack of donors. Therefore, dialysis has become the standard treatment for ESKD patients. However, the optimal dialysis method for diabetic ESKD patients remains controversial. ESKD patients with diabetes often present with complex conditions and numerous complications. Furthermore, these patients face a high risk of infection and technical failure, are more susceptible to malnutrition, have difficulty establishing vascular access, and experience more frequent blood sugar fluctuations than the general population. Therefore, this article reviews nine critical aspects: Survival rate, glucose metabolism disorder, infectious complications, cardiovascular events, residual renal function, quality of life, economic benefits, malnutrition, and volume load. This study aims to assist clinicians in selecting individualized treatment methods by comparing the advantages and disadvantages of hemodialysis and peritoneal dialysis, thereby improving patients' quality of life and survival rates.

Does tea intake increase the risk of anemia? Evidence from a large prospective cohort and Mendelian randomization study.

Tea consumption is avoided by some due to concerns about its potential to cause anemia. To clarify this impact, we assessed the association between tea intake and anemia in a Chinese prospective cohort study and by Mendelian randomization (MR). We analyzed associations of tea intake with anemia using data from the baseline (N = 30 085) and three subsequent follow-ups (the first: N = 17 898; the second: N = 10 435; the third: N = 5311) in the Guangzhou Biobank Cohort Study (GBCS). We also assessed the causal effect of tea intake on anemia, hemoglobin (Hgb) and hematocrit (Hct) using two-sample MR with summary statistics from relevant genome-wide association studies and the UK Biobank (N = 447 485). At the baseline, compared with never-drinkers, regular tea drinkers had higher levels of Hgb and Hct and a lower risk of anemia after adjustment for confounders (all P < 0.05; all P for trend ≤0.006). Prospectively, compared with never-drinkers, regular tea drinkers had higher Hgb (g L-1) (ß = 0.69; 95% CI, 0.28 to 1.10; P for trend <0.001) and Hct (%) (ß = 0.30; 95% CI, 0.19 to 0.41; P for trend <0.001), but no significant difference in anemia risk (OR = 0.91; 95% CI, 0.82 to 1.02; P for trend = 0.071). MR analyses showed no association between tea intake and anemia, Hgb and Hct. Through triangulation of evidence using a Chinese cohort and genetics, tea consumption appears unlikely to impact anemia risk.

Hydrogel Microneedle Patches Loaded with Stem Cell Mitochondria-Enriched Microvesicles Boost the Chronic Wound Healing.

Rescuing or compensating mitochondrial function represents a promising therapeutic avenue for radiation-induced chronic wounds. Adult stem cell efficacies are primarily dependent on the paracrine secretion of mitochondria-containing extracellular vesicles (EVs). However, effective therapeutic strategies addressing the quantity of mitochondria and mitochondria-delivery system are lacking. Thus, in this study, we aimed to design an effective hydrogel microneedle patch (MNP) loaded with stem cell-derived mitochondria-rich EVs to gradually release and deliver mitochondria into the wound tissues and boost wound healing. We, first, used metformin to enhance mitochondrial biogenesis and thereby increasing the secretion of mitochondria-containing EVs (termed "Met-EVs") in adipose-derived stem cells. To verify the therapeutic effects of Met-EVs, we established an in vitro and an in vivo model of X-ray-induced mitochondrial dysfunction. The Met-EVs ameliorated the mitochondrial dysfunction by rescuing mitochondrial membrane potential, increasing adenosine 5'-triphosphate levels, and decreasing reactive oxygen species production by transferring active mitochondria. To sustain the release of EVs into damaged tissues, we constructed a Met-EVs@Decellularized Adipose Matrix (DAM)/Hyaluronic Acid Methacrylic Acid (HAMA)-MNP. Met-EVs@DAM/HAMA-MNP can load and gradually release Met-EVs and their contained mitochondria into wound tissues to alleviate mitochondrial dysfunction. Moreover, we found Met-EVs@DAM/HAMA-MNP can markedly promote macrophage polarization toward the M2 subtype with anti-inflammatory and regenerative functions, which can, in turn, enhance the healing process in mice with skin wounds combined radiation injuries. Collectively, we successfully fabricated a delivery system for EVs, Met-EVs@DAM/HAMA-MNP, to effectively deliver stem cell-derived mitochondria-rich EVs. The effectiveness of this system has been demonstrated, holding great potential for chronic wound treatments in clinic.

Active longevity and aging: dissecting the impacts of physical and sedentary behaviors on longevity and age acceleration.

BACKGROUND: To examine the associations of physical activity (PA) and sedentary behavior (SB) with longevity and age acceleration (AA) using observational and Mendelian randomization (MR) studies, and quantify the mediating effects of lipids. METHODS: In Guangzhou Biobank Cohort Study (GBCS), PA and SB were assessed by the Chinese Version of the International Physical Activity Questionnaire. Longevity was defined as participants whose age at follow-up or at death was at or above the 90th age percentile. AA was defined as the residual resulting from a linear model that regressed phenotypic age against chronological age. Linear regression and Poisson regression with robust error variance were used to assess the associations of total and specific PA in different intensities, and SB with AA and longevity, yielding ßs or relative risks (RRs) and 95% confidence intervals (CIs). Two-sample MR was conducted to examine the causal effects. Mediation analysis was used to assess the mediating effects of lipids. RESULTS: Of 20,924 participants aged 50 + years in GBCS, during an average follow-up of 15.0 years, compared with low PA, moderate and high PA were associated with higher likelihood of longevity (RR (95% CI): 1.56 (1.16, 2.11), 1.66 (1.24, 2.21), respectively), and also cross-sectionally associated with lower AA (ß (95% CI): -1.43 (-2.41, -0.45), -2.09 (-3.06, -1.11) years, respectively). Higher levels of moderate PA (MPA) were associated with higher likelihood of longevity and lower AA, whereas vigorous PA (VPA) showed opposite effects. The association of PA with longevity observed in GBCS was mediated by low-density lipoprotein cholesterol (LDL-C) by 8.23% (95% CI: 3.58-39.61%), while the association with AA was mediated through LDL-C, triglycerides and total cholesterol by 5.13% (3.94-7.30%), 7.81% (5.98-11.17%), and 3.37% (2.59-4.80%), respectively. Additionally, in two-sample MR, SB was positively associated with AA (ß (95% CI): 1.02 (0.67, 1.36) years). CONCLUSIONS: PA showed protective effects on longevity and AA, with the effects being partly mediated through lipids. Conversely, SB had a detrimental impact on AA. MPA was associated with higher likelihood of longevity and reduced AA, whereas VPA showed adverse effects. Our findings reinforce the recommendation of "sit less and move more" to promote healthy longevity, and highlight the potential risks associated with VPA in the elderly.

A Prediction Model for Detecting Dysthyroid Optic Neuropathy Based on Clinical Factors and Imaging Markers of the Optic Nerve and Cerebrospinal Fluid in the Optic Nerve Sheath.

OBJECTIVE: This study aimed to develop and test a model for predicting dysthyroid optic neuropathy (DON) based on clinical factors and imaging markers of the optic nerve and cerebrospinal fluid (CSF) in the optic nerve sheath. METHODS: This retrospective study included patients with thyroid-associated ophthalmopathy (TAO) without DON and patients with TAO accompanied by DON at our hospital. The imaging markers of the optic nerve and CSF in the optic nerve sheath were measured on the water-fat images of each patient and, together with clinical factors, were screened by Least absolute shrinkage and selection operator. Subsequently, we constructed a prediction model using multivariate logistic regression. The accuracy of the model was verified using receiver operating characteristic curve analysis. RESULTS: In total, 80 orbits from 44 DON patients and 90 orbits from 45 TAO patients were included in our study. Two variables (optic nerve subarachnoid space and the volume of the CSF in the optic nerve sheath) were found to be independent predictive factors and were included in the prediction model. In the development cohort, the mean area under the curve (AUC) was 0.994, with a sensitivity of 0.944, specificity of 0.967, and accuracy of 0.901. Moreover, in the validation cohort, the AUC was 0.960, the sensitivity was 0.889, the specificity was 0.893, and the accuracy was 0.890. CONCLUSIONS: A combined model was developed using imaging data of the optic nerve and CSF in the optic nerve sheath, serving as a noninvasive potential tool to predict DON.

Anti-inflammatory and DNA Repair Effects of Astragaloside IV on PC12 Cells Damaged by Lipopolysaccharide.

OBJECTIVE: This study aimed to establish a neural cell injury model in vitro by stimulating PC12 cells with lipopolysaccharide (LPS) and to examine the effects of astragaloside IV on key targets using high-throughput sequence technology and bioinformatics analyses. METHODS: PC12 cells in the logarithmic growth phase were treated with LPS at final concentrations of 0.25, 0.5, 0.75, 1, and 1.25 mg/mL for 24 h. Cell morphology was evaluated, and cell survival rates were calculated. A neurocyte inflammatory model was established with LPS treatment, which reached a 50% cell survival rate. PC12 cells were treated with 0.01, 0.1, 1, 10, or 100 µmol/L astragaloside IV for 24 h. The concentration of astragaloside IV that did not affect the cell survival rate was selected as the treatment group for subsequent experiments. NOS activity was detected by colorimetry; the expression levels of ERCC2, XRCC4, XRCC2, TNF-α, IL-1ß, TLR4, NOS and COX-2 mRNA and protein were detected by RT-qPCR and Western blotting. The differentially expressed genes (DEGs) between the groups were screened using a second-generation sequence (fold change>2, P<0.05) with the following KEGG enrichment analysis, RT-qPCR and Western blotting were used to detect the mRNA and protein expression of DEGs related to the IL-17 pathway in different groups of PC12 cells. RESULTS: The viability of PC12 cells was not altered by treatment with 0.01, 0.1, or 1 µmol/L astragaloside IV for 24 h (P>0.05). However, after treatment with 0.5, 0.75, 1, or 1.25 mg/mL LPS for 24 h, the viability steadily decreased (P<0.01). The mRNA and protein expression levels of ERCC2, XRCC4, XRCC2, TNF-α, IL-1ß, TLR4, NOS, and COX-2 were significantly increased after PC12 cells were treated with 1 mg/mL LPS for 24 h (P<0.01); however, these changes were reversed when PC12 cells were pretreated with 0.01, 0.1, or 1 µmol/L astragaloside IV in PC12 cells and then treated with 1 mg/mL LPS for 24 h (P<0.05). Second-generation sequencing revealed that 1026 genes were upregulated, while 1287 genes were downregulated. The DEGs were associated with autophagy, TNF-α, interleukin-17, MAPK, P53, Toll-like receptor, and NOD-like receptor signaling pathways. Furthermore, PC12 cells treated with a 1 mg/mL LPS for 24 h exhibited increased mRNA and protein expression of CCL2, CCL11, CCL7, MMP3, and MMP10, which are associated with the IL-17 pathway. RT-qPCR and Western blotting analyses confirmed that the DEGs listed above corresponded to the sequence assay results. CONCLUSION: LPS can damage PC12 cells and cause inflammatory reactions in nerve cells and DNA damage. astragaloside IV plays an anti-inflammatory and DNA damage protective role and inhibits the IL-17 signaling pathway to exert a neuroprotective effect in vitro.

Proteomics analysis of immune response-related proteins in Guillain-Barré Syndrome (GBS) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP).

The objective is to characterize differentially expressed proteins (DEPs) in Guillain-Barré Syndrome (GBS) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) through high-throughput analysis. Sera from 11 healthy controls (HCs), 21 GBS and 19 CIDP patients were subjected to Olink Proteomics Analysis. In the comparison between CIDP and GBS groups, up-regulation of ITM2A and down-regulation of NTF4 were observed. Comparing GBS with HCs revealed 18 up-regulated and 4 down-regulated proteins. Comparing CIDP with the HCs identified 15 up-regulated and 4 down-regulated proteins. Additionally, the correlation between clinical characteristics and DEPs were uncovered. In conclusion, the DEPs have significant potential to advance our understanding of the pathogenesis in these debilitating neurological disorders.

Zürich II Statement on Per- and Polyfluoroalkyl Substances (PFASs): Scientific and Regulatory Needs.

Per- and polyfluoroalkyl substances (PFASs) are a class of synthetic organic chemicals of global concern. A group of 36 scientists and regulators from 18 countries held a hybrid workshop in 2022 in Zürich, Switzerland. The workshop, a sequel to a previous Zürich workshop held in 2017, deliberated on progress in the last five years and discussed further needs for cooperative scientific research and regulatory action on PFASs. This review reflects discussion and insights gained during and after this workshop and summarizes key signs of progress in science and policy, ongoing critical issues to be addressed, and possible ways forward. Some key take home messages include: 1) understanding of human health effects continues to develop dramatically, 2) regulatory guidelines continue to drop, 3) better understanding of emissions and contamination levels is needed in more parts of the world, 4) analytical methods, while improving, still only cover around 50 PFASs, and 5) discussions of how to group PFASs for regulation (including subgroupings) have gathered momentum with several jurisdictions proposing restricting a large proportion of PFAS uses. It was concluded that more multi-group exchanges are needed in the future and that there should be a greater diversity of participants at future workshops.

Association between operative position and postoperative nausea and vomiting in patients undergoing laparoscopic sleeve gastrectomy.

BACKGROUND: Bariatric surgery is one of the most effective ways to treat morbid obesity, and postoperative nausea and vomiting (PONV) is one of the common complications after bariatric surgery. At present, the mechanism of the high incidence of PONV after weight-loss surgery has not been clearly explained, and this study aims to investigate the effect of surgical position on PONV in patients undergoing bariatric surgery. AIM: To explore the effect of the operative position during bariatric surgery on PONV. METHODS: Data from obese patients, who underwent laparoscopic sleeve gastrectomy (LSG) in the authors' hospital between June 2020 and February 2022 were divided into 2 groups and retrospectively analyzed. Multivariable logistic regression analysis and the t-test were used to study the influence of operative position on PONV. RESULTS: There were 15 cases of PONV in the supine split-leg group (incidence rate, 50%) and 11 in the supine group (incidence rate, 36.7%) (P = 0.297). The mean operative duration in the supine split-leg group was 168.23 ± 46.24 minutes and 140.60 ± 32.256 minutes in the supine group (P < 0.05). Multivariate analysis revealed that operative position was not an independent risk factor for PONV (odds ratio = 1.192, 95% confidence interval: 0.376-3.778, P = 0.766). CONCLUSION: Operative position during LSG may affect PONV; however, the difference in the incidence of PONV was not statistically significant. Operative position should be carefully considered for obese patients before surgery.

The monkeypox virus-host interplays.

Monkeypox virus (MPXV) is a DNA virus belonging to the Orthopoxvirus genus within the Poxviridae family which can cause a zoonotic infection. The unexpected non-endemic outbreak of mpox in 2022 is considered as a new global threat. It is imperative to take proactive measures, including enhancing our understanding of MPXV's biology and pathogenesis, and developing novel antiviral strategies. The host immune responses play critical roles in defensing against MPXV infection while the virus has also evolved multiple strategies for immune escape. This review summarizes the biological features, antiviral immunity, immune evasion mechanisms, pathogenicity, and prevention strategies for MPXV.

Childhood socio-economic disadvantages versus adverse care experiences: Mediation and moderation impacts on late-life depressive symptoms.

BACKGROUND: Whether material deprivation-related childhood socio-economic disadvantages (CSD) and care-related adverse childhood experiences (ACE) have different impacts on depressive symptoms in middle-aged and older people is unclear. METHODS: In the Guangzhou Biobank Cohort Study, CSD and ACE were assessed by 7 and 5 culturally sensitive questions, respectively, on 8,716 participants aged 50+. Depressive symptoms were measured by 15-item Geriatric Depression Scale (GDS). Multivariable linear regression, stratification analyses, and mediation analyses were done. RESULTS: Higher CSD and ACE scores were associated with higher GDS score in dose-response manner (P for trend <0.001). Participants with one point increment in CSD and ACE had higher GDS score by 0.11 (95% confidence interval [CI], 0.09-0.14) and 0.41 (95% CI, 0.35-0.47), respectively. The association of CSD with GDS score was significant in women only (P for sex interaction <0.001; women: ß (95% CI)=0.14 (0.11-0.17), men: 0.04 (-0.01 to 0.08)). The association between ACE and GDS score was stronger in participants with high social deprivation index (SDI) (P for interaction = 0.01; low SDI: ß (95% CI)=0.36 (0.29-0.43), high SDI: 0.64 (0.48-0.80)). The proportion of association of CSD and ACE scores with GDS score mediated via education was 20.11% and 2.28%. CONCLUSIONS: CSD and ACE were associated with late-life depressive symptoms with dose-response patterns, especially in women and those with low adulthood socio-economic status. Education was a major mediator for CSD but not ACE. Eliminating ACE should be a top priority.