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.

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.

Association of serum pertussis antibodies with acute asthma attacks in children.

Objective: The aim of this study was to examine the serum antibody levels against pertussis toxin (PT) in children experiencing an acute asthma attack and to explore the potential association between these levels and asthma. Methods: A prospective investigation was conducted, which involved 107 children with acute asthma attacks and 77 children diagnosed with bronchitis. The serum immunoglobulin G (IgG) antibody levels specific to PT were measured by using an in-house enzyme-linked immunosorbent assay. Based on the serum PT-IgG antibody levels, the children with asthma were categorized into three groups: non-pertussis infected, suspected pertussis infected, and recent pertussis infected. The clinical manifestations and pulmonary function of pediatric patients diagnosed with asthma were assessed and compared across various groups. Results: Of the total asthma group, 25 patients tested positive for PT-IgG, whereas only six patients in the bronchitis group were PT-IgG positive. The prevalence of recent pertussis infection was observed to be higher in the asthma group compared with the bronchitis group. Within the asthma group, those with recent pertussis infection exhibited a higher likelihood of experiencing wheezing and impaired lung function in comparison with the non-pertussis infection group. Conclusion: Pertussis infection is relatively common in children with asthma and correlates with the severity of asthma.

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.

[Activated phosphoinositide 3-kinase delta syndrome: report of seven cases]. / PI3Kδ过度活化综合征7例报道.

OBJECTIVES: To summarize the clinical data of 7 children with activated phosphoinositide 3-kinase delta syndrome (APDS) and enhance understanding of the disease. METHODS: A retrospective analysis was conducted on clinical data of 7 APDS children admitted to Hunan Provincial People's Hospital from January 2019 to August 2023. RESULTS: Among the 7 children (4 males, 3 females), the median age of onset was 30 months, and the median age at diagnosis was 101 months. Recurrent respiratory tract infections, hepatosplenomegaly, and multiple lymphadenopathy were observed in all 7 cases. Sepsis was observed in 5 cases, otitis media and multiple caries were observed in 3 cases, and diarrhea and joint pain were observed in 2 cases. Lymphoma and systemic lupus erythematosus were observed in 1 case each. Fiberoptic bronchoscopy was performed in 4 cases, revealing scattered nodular protrusions in the bronchial lumen. The most common respiratory pathogen was Streptococcus pneumoniae (4 cases). Six patients had a p.E1021K missense mutation, and one had a p.434-475del splice site mutation. CONCLUSIONS: p.E1021K is the most common mutation site in APDS children. Children who present with one or more of the following symptoms: recurrent respiratory tract infections, hepatosplenomegaly, multiple lymphadenopathy, otitis media, and caries, and exhibit scattered nodular protrusions on fiberoptic bronchoscopy, should be vigilant for APDS. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(5): 499-505.

[Value of calprotectin S100 A8/A9 in predicting the severity of Mycoplasma pneumoniae pneumonia in children]. / 钙卫蛋白S100 A8/A9å¯¹è‚ºç‚Žæ”¯åŽŸä½“è‚ºç‚Žæ‚£å„¿ç— æƒ ä¸¥é‡ç¨‹åº¦çš„é¢„æµ‹ä»·å€¼.

OBJECTIVES: To investigate the role of calprotectin S100 A8/A9 complex in evaluating the condition of children with severe Mycoplasma pneumoniae pneumonia (SMPP). METHODS: A prospective study was conducted among 136 children with Mycoplasma pneumoniae pneumonia (MPP) and 30 healthy controls. According to the severity of the condition, the children with MPP were divided into mild subgroup (40 children) and SMPP subgroup (96 children). The levels of S100 A8/A9 complex and related inflammatory factors were compared between the MPP group and the healthy control group, as well as between the two subgroups of MPP. The role of S100 A8/A9 in assessing the severity of MPP was explored. RESULTS: The MPP group had a significantly higher level of S100 A8/A9 than the healthy control group, with a significantly greater increase in the SMPP subgroup (P<0.05). The multivariate logistic regression analysis showed that the increases in serum C reactive protein (CRP) and S100A8/A9 were closely associated with SMPP (P<0.05). The receiver operating characteristic (ROC) curve analysis showed that the combined measurement of serum S100 A8/A9 and CRP had an area under the ROC curve of 0.904 in predicting SMPP, which was significantly higher than the AUC of S100 A8/A9 or CRP alone (P<0.05), with a specificity of 0.718 and a sensitivity of 0.952. CONCLUSIONS: S100 A8/A9 is closely associated with the severity of MPP, and the combination of S100 A8/A9 with CRP is more advantageous for assessing the severity of MPP in children.

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.

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.

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.

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.

circ-AKT3 aggravates renal ischaemia-reperfusion injury via regulating miR-144-5p /Wnt/ß-catenin pathway and oxidative stress.

Renal ischaemia-reperfusion (RI/R) injury is one major pathological state of acute kidney injury (AKI) with a mortality rate ranking 50% to 80%. MiR-144-5p acts as a molecular trigger in various diseases. We presumed that miR-144-5p might be involved RI/R injury progression. We found that RI/R injury decreased miR-144-5p expression in rat models. MiR-144-5p downregulation promoted cell apoptosis rate and activated Wnt/ß-catenin signal in RI/R injury rats. By performing bioinformatic analysis, RIP, RNA pull-down, luciferase reporter experiments, we found that circ-AKT3 sponged to miR-144-5p and decreased its expression in RI/R injury rats. Moreover, we found that circ-AKT3 promoted cell apoptosis rate and activated Wnt/ß-catenin signal, and miR-144-5p mimic reversed the promotive effect of circ-AKT3 in rat models. We also found that circ-AKT3 increased the oxidative stress level in rat models. In conclusion, our study suggests that the circAKT3 is involved RI/R injury progression through regulating miR-144-5p/Wnt/ß-catenin pathway and oxidative stress.

Zuogui Pill Attenuates Neuroinflammation and Improves Cognitive Function in Cerebral Ischemia Reperfusion-Injured Rats.

INTRODUCTION: Cerebral ischemia and reperfusion (CI/R) injury is a devasting cerebrovascular disease, accompanied with ischemia stroke, cerebral infarction. Zuogui Pill (ZGP), as a Chinese traditional medicine, is proved to be effective in many diseases and cancers. Our study aimed to detect the roles of ZGP in CI/R injury. METHODS: Neural stem cells were isolated from rats and induced by oxygen and glucose deprivation and recovery. CCK-8 and flow cytometry were applied to assess the function of ZGP on cell viability and apoptosis. Rat CI/R injury models were established by the middle cerebral artery occlusion and reperfusion. The function of ZGP on CI/R injury was identified via evaluating modified neurological severity score, infarct area, and cognitive impairment. RESULTS: Compared to the control, the cell viability was obviously decreased in the oxygen and glucose deprivation and recovery (OGD/R) group, while the adverse influence on cells was reversed by cultured plus 10% ZGP serum. Consistently, ZGP attenuated the influence of OGD/R on cell apoptosis. More importantly, ZGP could alleviate CI/R injury of rats by reducing neurological damage and infarct area and promoting cognitive function. CONCLUSION: This study provided protective roles of ZGP on cell viability and apoptosis induced by OGD/R. In addition, ZGP played protective roles on neuroinflammation and cognitive function in rats.

Zuoguiwan Ameliorates Cognitive Deficits and Neuro-Inflammation in Streptozotocin-Induced Alzheimer's Disease Rats.

INTRODUCTION: Alzheimer's disease is the most popular neurodegenerative disorder with no effective drugs to stop the progression. Zuoguiwan (ZGW), a traditional Chinese herbal medicine, has been applied in many diseases. Our study aimed to detect the function and mechanisms of ZGW in Alzheimer's disease (AD). METHODS: The rat models of AD were established by streptozotocin (STZ), and the function of ZGW on cognitive dysfunction was measured with the Morris water maze test. The concentration of pro-inflammatory mediators was accessed by enzyme-linked immunosorbent assay. The relative mRNA expression of ERß was detected by real-time quantitative PCR. RESULTS: The treatment with ZGW could suppress the cognitive impairment by the findings of escape latency and time spent in the target quadrant and the increased concentration of IL-1ß, IL-6, and TNF-α induced by STZ. STZ might repress the mRNA levels of ERß, and ZGW management weakened the declined mRNA expression of ERß. ZGW might play a protective role in AD rats against the injury of STZ on cognition and neuro-inflammation by improving the mRNA expression of ERß. CONCLUSION: The results indicated that ZGW might be a novel therapeutic strategy to slow the process of AD by modulating ERß.

Diagnostic accuracy of DNA-based SDC2 methylation test in colorectal cancer screening: a meta-analysis.

BACKGROUND: A growing body of research suggests that methylated genes can be used as early diagnostic markers for cancer. Some studies on methylated Syndecan 2 (SDC2) have shown that it has a great diagnostic ability in colorectal cancer. This meta-analysis was aimed to estimate the diagnostic performance of methylated SDC2 as a potential novel biomarker to screen for the colorectal cancer. METHODS: Two independent researchers conducted a comprehensive literature search to identify all relevant studies on SDC2 methylation for the diagnosis of colorectal cancer from inception to March 1, 2021. By using STATA and Revman software, the data were analyzed using a Bivariate mixed model. The quality of each study was also evaluated. RESULTS: A total of 12 studies comprised of 1574 colorectal cancer patients and 1945 healthy people were included in our meta-analysis. Bivariate analysis showed a pooled sensitivity of 0.81 [95% confidence interval (CI) 0.74-0.86], specificity of 0.95 (95% CI 0.93-0.96), positive likelihood ratio of 15.29 (95% CI 10.83-21.60), and negative likelihood ratio of 0.21 (95% CI 0.15-0.27). The diagnostic odds ratio and the area under the summary ROC curve for diagnosing colorectal cancer were 74.42 (95% CI45.44-121.89) and 0.96 (95% CI 0.94-0.97), respectively. For adenomas, the pooled sensitivity and specificity were 0.47 (95% CI 0.34-0.61) and 0.95 (95% CI 0.92-0.97), respectively. CONCLUSIONS: Our analysis revealed that methylated SDC2 could be considered as a potential novel biomarker to screen for colorectal cancer.

Plasma Fluorescent Oxidation Products and Bone Mineral Density Among Male Veterans: A Cross-Sectional Study.

In vitro and vivo studies indicate that oxidative stress contributes to bone loss. Fluorescent oxidation products (FlOPs) are novel biomarkers of oxidative stress; they reflect global oxidative damage of lipids, proteins, carbohydrates, and DNA. However, whether FlOPs are associated with bone mineral density (BMD) is still unclear. In the present study, we examined the association between FlOPs and BMD among male veterans. This cross-sectional study was conducted among participants recruited from the Department of Medical Examination, The Second Hospital of Jilin University in Jilin, China. We identified male veterans who were at least 50 y old between June and October of 2019. Plasma FlOPs were measured with a fluorescent microplate reader (excitation/emission wavelength: 320/420 nm). BMD were measured by dual-energy X-ray absorptiometry (DXA). The association between FlOPs and BMD was tested by multivariable linear regression models. A total of 164 male veterans were enrolled in the study, the average age was 56.6 y. After adjusting for covariates, veterans who had FlOP levels in the highest tertile had a statistically significant lower femoral neck (ß = -0.044; p = 0.007) and total hip BMD (ß = -0.045; p = 0.020) as compared to those with FlOP levels in the lowest tertile. Similar results were found when FlOPs were treated as a continuous variable (per 1-SD increase, ß = -0.014 and p = 0.033 for femoral neck BMD; ß = -0.016 and p = 0.047 for total hip BMD). Higher FlOP levels were associated with lower BMD among male veterans.

Efficient and risk-reduced genome editing using double nicks enhanced by bacterial recombination factors in multiple species.

Site-specific DNA double-strand breaks have been used to generate knock-in through the homology-dependent or -independent pathway. However, low efficiency and accompanying negative impacts such as undesirable indels or tumorigenic potential remain problematic. In this study, we present an enhanced reduced-risk genome editing strategy we named as NEO, which used either site-specific trans or cis double-nicking facilitated by four bacterial recombination factors (RecOFAR). In comparison to currently available approaches, NEO achieved higher knock-in (KI) germline transmission frequency (improving from zero to up to 10% efficiency with an average of 5-fold improvement for 8 loci) and 'cleaner' knock-in of long DNA fragments (up to 5.5 kb) into a variety of genome regions in zebrafish, mice and rats. Furthermore, NEO yielded up to 50% knock-in in monkey embryos and 20% relative integration efficiency in non-dividing primary human peripheral blood lymphocytes (hPBLCs). Remarkably, both on-target and off-target indels were effectively suppressed by NEO. NEO may also be used to introduce low-risk unrestricted point mutations effectively and precisely. Therefore, by balancing efficiency with safety and quality, the NEO method reported here shows substantial potential and improves the in vivo gene-editing strategies that have recently been developed.

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.

Knowledge Difference of Tumor Nutrition Risk Among Thoracic Cancer Patients, Their Family Members, Physicians, and Nurses.

To investigate the difference among patients, family members, physicians, and nurses in their ability to identify malnutrition risk in patients with thoracic cancer. The enrolled patients were evaluated by the NRS2002 nutritional risk scale. The patient-centered groups, including the patient, the primary caretaker, the physician, and the nurse, were given a questionnaire on their knowledge and understanding of nutrition therapy in cancer treatment. The incidence rate of nutritional risk in hospitalized patients with thoracic cancer was 13.8%. There were significant differences in the accuracy rate of nutritional risk assessment among the four groups (P < 0.001), in which the nurses' was 70.3%, 55.1% for the physician, 38.7% for family members, and 33.0% for patients, which was the poorest accuracy rate. No significant correlation was found between the accuracy of nutritional risk assessment and the education level and personal monthly income of each population (P > 0.05). Nearly all four groups considered it necessary to learn more about cancer nutrition therapy. For patients and their families, the main way to understand the knowledge of tumor nutrition was consultation with medical staff and information exchange between patients; for doctors, new media; and for nurses, classroom training. Nurses' assessment of nutritional risk in cancer patients achieved the highest accuracy, while the poorest accuracy originated from the patients.

["Massive hemoptysis" and shock after fever and cough]. / 发热咳嗽后大"咯血"ä¼‘å ‹.

A boy, aged 11 years, was admitted due to intermittent fever for 15 days, cough for 10 days, and "hemoptysis" for 7 days. The boy had fever and cough with left neck pain 15 days ago, and antibiotic treatment was effective. During the course of disease, the boy developed massive "hemoptysis" which caused shock. Fiberoptic bronchoscopy revealed a left pyriform sinus fistula with continuous bleeding. In combination with neck and vascular imaging examination results, the boy was diagnosed with internal jugular vein injury and thrombosis due to congenital pyriform sinus fistula infection and neck abscess. The boy was improved after treatment with temperature-controlled radiofrequency ablation for the closure of pyriform sinus fistula, and no recurrence was observed during the follow-up for one year and six months. No reports of massive hemorrhage and shock due to pyriform sinus fistula infection were found in the searched literature, and this article summarizes the clinical features, diagnosis, and treatment of this boy, so as to provide a reference for the early diagnosis of such disease and the prevention and treatment of its complications.