[Association between onset time of sepsis-associated acute kidney injury and clinical outcome in patients with sepsis].

Objective: To explore the relationship between the onset time of sepsis-associated acute kidney injury (SA-AKI) and adverse clinical outcomes. Methods: Data were derived from Beijing Acute Kidney Injure Trial (BAKIT) which investigated the epidemiology of acute kidney injury (AKI) in critically ill patients at 30 intensive care units (ICU) of 28 tertiary hospitals in Beijing from 1 March to 31 August 2012. Patients who were older than 18 years and diagnosed with sepsis and AKI, and expected to stay in ICU for at least 24 h were included in this study. A total of 653 patients were included in this study, 414 males and 239 females with a mean age of (68.2±17.0) years. According to the onset time of SA-AKI, patients were grouped into early AKI (E-AKI) (AKI occurred within 48 hours after ICU admission) and late AKI (L-AKI) (AKI occurred after 48 hours of ICU admission) group. The primary outcome was major adverse kidney events (MAKE), consisted of all-cause mortality, renal replacement therapy-dependence, and an inability to recover to 1.5 times of the baseline creatinine value up to 30 days. Multivariable logistic regression was used to investigate the association between the onset time of SA-AKI and clinical outcomes. Results: A total of 653 patients with SA-AKI were included, 423 (64.8%) patients developed E-AKI, 230 (35.2%) cases developed L-AKI, MAKE occurred in 405 (62.0%) cases, and 301 (46.1%) patients died in hospital. Compared with E-AKI group, L-AKI patients showed higher AKI 3 level rate [55.7%(128/230) vs 40.2%(170/423), P<0.001], incidence of MAKE [72.6%(167/230) vs 56.3%(238/423,P<0.001)] and hospital mortality [55.2%(127/230) vs 44.1%(174/423), P=0.001]. The risk of MAKE and in-hospital mortality in L-AKI group increased for 2.55-fold times (OR=3.55, 95%CI: 1.94-6.04) and 1.84-fold times (OR=2.84, 95%CI: 1.44-5.60) when compared with those in E-AKI, respectively (both P<0.05). Conclusion: Late timing onset of SA-AKI is associated with poor clinical outcomes.

Mechanism studies for relativistic attosecond electron bunches from laser-illuminated nanotargets.

To find a way to control the electron-bunching process and the bunch-emitting directions when an ultraintense, linearly polarized laser pulse interacts with a nanoscale target, we explored the mechanisms for the periodical generation of relativistic attosecond electron bunches. By comparing the simulation results of three different target geometries, the results show that for nanofoil target, limiting the transverse target size to a small value and increasing the longitudinal size to a certain extent is an effective way to improve the total electron quantity in a single bunch. Then the subfemtosecond electronic dynamics when an ultrashort ultraintense laser grazing propagates along a nanofoil target was analyzed through particle-in-cell simulations and semiclassical analyses, which shows the detailed dynamics of the electron acceleration, radiation, and bunching process in the laser field. The analyses also show that the charge separation field produced by the ions plays a key role in the generation of electron bunches, which can be used to control the quantity of the corresponding attosecond radiation bunches by adjusting the length of the nanofoil target.

[Epidemiological investigation of iron deficiency among preschool children in 10 provinces, autonomous regions, or municipalities in China].

Objective: To understand the current status of anemia, iron deficiency, and iron-deficiency anemia among preschool children in China. Methods: A cross-sectional study was conducted with a multi-stage stratified sampling method to select 150 streets or townships from 10 Chinese provinces, autonomous regions, or municipalities (East: Jiangsu, Zhejiang, Shandong, and Hainan; Central: Henan; West: Chongqing, Shaanxi, Guizhou, and Xinjiang; Northeast: Liaoning). From May 2022 to April 2023, a total of 21 470 children, including community-based children aged 0.5 to<3.0 years receiving child health care and kindergarten-based children aged 3.0 to<7.0 years, were surveyed. They were divided into 3 age groups: infants (0.5 to<1.0 year), toddlers (1.0 to<3.0 years), and preschoolers (3.0 to<7.0 years). Basic information such as sex and date of birth of the children was collected, and peripheral blood samples were obtained for routine blood tests and serum ferritin measurement. The prevalence rates of anemia, iron deficiency, and iron-deficiency anemia were analyzed, and the prevalence rate differences were compared among different ages, sex, urban and rural areas, and regions using the chi-square test. Results: A total of 21 460 valid responses were collected, including 10 780 boys (50.2%). The number of infants, toddlers, and preschoolers were 2 645 (12.3%), 6 244 (29.1%), and 12 571 (58.6%), respectively. The hemoglobin level was (126.7±14.8) g/L, and the serum ferritin level was 32.3 (18.5, 50.1) µg/L. The overall rates of anemia, iron deficiency, and iron-deficiency anemia were 10.4% (2 230/21 460), 28.3% (6 070/21 460), and 3.9% (845/21 460), respectively. The prevalence rate of anemia was higher for boys than for girls (10.9% (1 173/10 780) vs. 9.9% (1 057/10 680), χ2=5.58, P=0.018), with statistically significant differences in the rates for infants, toddlers and preschoolers (18.0% (475/2 645), 10.6% (662/6 244), and 8.7% (1 093/12 571), respectively, χ2=201.81, P<0.01), and the rate was significantly higher for children in rural than that in urban area (11.8% (1 516/12 883) vs. 8.3% (714/8 577), χ2=65.54, P<0.01), with statistically significant differences in the rates by region (χ2=126.60, P<0.01), with the highest rate of 15.8% (343/2 173) for children in Central region, and the lowest rate of 5.3% (108/2 053) in Northeastern region. The prevalence rates of iron deficiency were 33.8% (895/2 645), 32.2% (2 011/6 244), and 25.2% (3 164/12 571) in infants, toddlers, and preschoolers, respectively, and 30.0% (3 229/10 780) in boys vs. 26.6% (2 841/10 680) in girls, 21.7% (1 913/8 821), 40.0% (870/2 173), 27.1% (2 283/8 413), 48.9% (1 004/2 053) in Eastern, Central, Western, and Northeastern regions, respectively, and each between-group showed a significant statistical difference (χ2=147.71, 29.73, 773.02, all P<0.01). The prevalence rate of iron-deficiency anemia showed a significant statistical difference between urban and rural areas, 2.9% (251/8 577) vs. 4.6% (594/12 883) (χ2=38.62, P<0.01), while the difference in iron deficiency prevalence was not significant (χ2=0.51, P=0.476). Conclusions: There has been a notable improvement in iron deficiency and iron-deficiency anemia among preschool children in China, but the situation remains concerning. Particular attention should be paid to the prevention and control of iron deficiency and iron-deficiency anemia, especially among infants and children in the Central, Western, and Northeastern regions of China.

Correlation between neuregulin receptor degradation protein-1 and Crohn's disease.

Neuregulin receptor degradation protein-1 (Nrdp1) is a newly discovered E3 ligase that plays a role in the apoptosis process of multiple diseases. Previous studies has shown that Nrdp1 exerted a proapoptotic effect in cardiac diseases. The purpose of this study is to investigate the potential involvement of Nrdp1 in the pathological processes of inflammatory bowel disease (IBD). To create a mouse model of experimental colitis, trinitrobenzenesulfonic acid (TNBS) was administered and the severity of colitis was assessed based on changes in weight and histological scores. Using Western blot and immunohistochemistry, significant increase in Nrdp1 expression was observed in intestinal epithelial cells (IECs). This was accompanied with the up-regulation of cleaved PARP and active caspase-3 in IECs, indicating a potential function in IECs. To study this further, we built an in vitro model of tumor necrosis factor-alpha (TNF-α)-induced apoptosis using human IEC line HT-29 cells. When Nrdp1 was knocked down, a decrease in apoptosis was observed, suggesting that Nrdp1 may play a proapoptotic role in IEC apoptosis. The mechanism behind this phenomenon is associated with the suppression of downstream targets of Nrdp1, such as protein kinase B (AKT). Furthermore, immunohistochemistry analysis in patients with Crohn's disease (CD) and normal controls supported the same results as observed in experimental colitis. We conclude that Nrdp1 may be a promising new therapeutic target for ameliorating IBD in humans.

[Efficiency of CNV-seq in detecting fetal DMD gene deletion or duplication in prenatal diagnosis].

Objective: To evaluate the diagnostic efficiency of copy number variation sequencing (CNV-seq) to detect the deletion or duplication of DMD gene in prenatal diagnosis. Methods: A retrospective analysis was carried out on the CNV-seq results of 34 544 fetuses diagnosed in the First People's Hospital of Yunnan Province from January 2018 to July 2023. A total of 156 cases of fetuses were collected, including Group 1:125 cases with family history of Duchenne muscular dystrophy or Becker muscular dystrophy (DMD/BMD), and Group 2:31 cases with no family history but a DMD gene deletion or duplication was detected unexpectedly by CNV-seq. Multiplex ligation-dependent probe amplification (MLPA) was used as a standard method to detect the deletion or duplication. Consistency test was carried out basing on the results of CNV-seq and MLPA of all 156 cases. Results: Comparing to MLPA, CNV-seq had a coincidence rate of 92.3% (144/156) for DMD gene deletion or duplication, with a sensitivity and positive predictive value of 88.2%, with a specificity and negative predictive value of 94.3%, a missed detection rate of 3.8%, and a Kappa value of 0.839. CNV-seq missed 4 cases with deletions and 2 with duplications due to involved fragments less than 100 Kb, among 20 cases of deletions and 6 cases of duplications detected by MLPA in Group 1. In Group 2, the deletions and duplications detected by CNV-seq were 42% (13/31) and 58% (18/31), respectively, in which the percentage of duplication was higher than that in Group 1. Among those 18 cases with duplications, 3 cases with duplication locating in exon 42~67 were likely pathogenic; while 9 cases with duplication covering the 5' or 3' end of the DMD gene, containing exon 1 or 79 and with only one breakpoint within the gene, along with the last 6 cases with duplications locating at chrX: 32650635_32910000 detected only by CNV-seq, which might be judged as variants of uncertain significance. Conclusions: CNV-seq has a good efficiency to detect fetal DMD gene deletion or duplication in prenatal diagnosis, while a further verification test by MLPA is recommended. The duplications on chrX: 32650635_32910000, 5' or 3' end of DMD gene detected by CNV-seq should be carefully verified and assessed because those variants appear to be nonpathogenic polymorphisms.

[Epidemiological characteristics of human respiratory syncytial virus among acute respiratory infection cases in 16 provinces of China from 2009 to 2023].

Objective: To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023. Methods: The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed. Results: A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M (Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant (P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age (P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion: Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.

[Wolfram-like syndrome: a case report].

Different from classical autosomal recessive Wolfram syndrome, Wolfram-like syndrome is an autosomal dominant disorder caused by a heterozygous mutation in the WFS1 gene. In this case, a 7-year-old male child presented to the eye clinic due to vision loss that could not be corrected, discovered during a routine examination. The child had experienced hearing impairment since early childhood, leading to cochlear implantation. Ophthalmic examination revealed optic disc atrophy in both eyes. Optical coherence tomography imaging demonstrated a distinctive thickening of the outer plexiform layer with abnormal layering, characteristic of a single mutation in the WFS1 gene. Subsequent genetic testing identified a de novo heterozygous missense mutation c.2051C>T (p.A684V) in the WFS1 gene, which ultimately led to the diagnosis of Wolfram-like syndrome.

Inulin has a beneficial effect by modulating the intestinal microbiome in a BALB/c mouse model.

Food allergy is an important health problem that affects human quality of life and socioeconomic development, and its treatment requires improvement. Intestinal flora dysbiosis is closely associated with food allergies. A sensitised mouse model was established by the intraperitoneal injection of ovalbumin (OVA). The mice were randomly divided into four groups: control, model, high-dose (H), and low-dose (L) inulin. The mice were administered water containing different concentrations of inulin four weeks before the OVA injection. Body weight changes were monitored. After the last OVA injection, the mice were scored for allergic reactions. The levels of total immunoglobulin E (IgE) and diamine oxidase (DAO) in the serum and secretory IgA (sIgA) in the small intestinal mucus were measured, and 16S rRNA sequencing of the faecal flora was performed to evaluate microbial parameters. The intestinal flora biomarkers, correlations between them, and biochemical indicators were analysed. Inulin treatment had no effect on the body weight of OVA-sensitised mice but attenuated allergic reactions and intestinal injury in mice. Compared with the control group, the model group had significantly higher levels of serum DAO and IgE and significantly lower levels of intestinal mucus IgA. IgA levels in the intestinal mucus of mice treated with inulin prior to OVA sensitisation were higher than those in non-inulin-treated OVA-sensitised mice. Furthermore, analysis of operational taxonomic units showed that inulin treatment decreased the abundance of Alloprevotella, Rikenellaceae RC9, Eubacterium siraeum, and Eubacterium xylanophilum, and increased the abundance of Blautia and Lachnospiraceae. Serum DAO levels were positively associated with Eubacterium siraeum, Alloprevotella, Eubacterium xylanophilum, and Odoribacter and negatively associated with Blautia, Tyzzerella, Alistipes, Desulfovibrionaceae, and Ruminococcaceae UCG005. In addition, IgE levels were positively associated with Eubacterium siraeum, Alloprevotella, Eubacterium xylanophilum, Odoribacter, and Citrobacter and negatively associated with Blautia, unclassified Ruminococcaceae, and Alistipes. IgA exhibited significant positive correlation with Blautia, norank_f_Eubacterium coprostanoligenes, Alistipes, norank Desulfovibrionaceae, Muribaculum, and Ruminococcaceae U C G 005 and significant negative correlation with Eubacterim siraeum, Eubacterium xylanophilum, Odoribacter, and Citrobacter. Inulin exerts a protective effect against food allergies in mice, which is partially mediated by alterations in the gut microbiota.

[Analysis of active surveillance results of pneumoconiosis in Jiangsu Province in 2019].

Objective: To conduct active surveillance of pneumoconiosis in Jiangsu Province in 2019, to understand the status quo of occupational health of dust-exposed workers, timely detect occupational health damage and occupational hazard factors, and provide scientific basis for the prevention and control of pneumoconiosis in the future. Methods: From January to December 2019, counties (cities and districts) with relatively concentrated dust hazard enterprises in Jiangsu Province were selected as monitoring points to carry out active surveillance of pneumoconiosis, and occupational health examination of dust workers (3540 people) in 255 enterprises were carried out, including chest radiographs and lung function examinations. SPSS 26.0 statistical software was used for statistical analysis of the data, and Chi-square test was used to analyze the difference level of the rate between different groups such as gender, age and service. Results: Among the 255 employers, small enterprises accounted for the highest proportion (186 enterprises, 72.94%), private economy accounted for the highest proportion (225 enterprises, 88.24%), and machinery manufacturing industry accounted for the highest proportion (44 enterprises, 17.25%). Among the 3540 workers exposed to dust, 6 suspected occupational diseases (0.17%), 50 occupational contraindications (1.41%), and 1469 other diseases or abnormalities (41.50%) were detected. Among the 3540 workers exposed to dust, 399 (11.27%) had abnormal chest radiography results, and 848 (23.95%) had abnormal lung function indicators. The abnormal detection rate of chest radiographs in males (12.25%, 359/2931) was higher than that in females (6.57%, 40/609), and the abnormal detection rate of lung function in females (32.18%, 196/609) was higher than that in males (22.24%, 652/2931), with statistical significance (P<0.05). The age of the workers exposed to dust ranged from 17 to 75 (41.78±10.39) years old, and the years of service in contact with dust of the workers ranged from 0.08 to 42 (6.72±7.47) years. There were statistically significant differences in the detection rate of abnormal chest radiography and abnormal lung function among different age and seniority workers (P<0.05). The abnormal rates of forced vital capacity (FVC), forced expiratory volume in the first second (FEV(1)) and FEV(1)/FVC were 13.79% (488/3540), 15.28% (541/3540) and 1.86% (66/3540), respectively. There were significant differences in the detection rate of abnormal chest radiography and abnormal lung function among workers exposed to different dust types (P<0.05) . Conclusion: There are few suspected occupational diseases detected by active surveillance of pneumoconiosis in Jiangsu Province in 2019, and there are differences in occupational health examination results among workers with different dust types, ages, genders and dust exposure years.

Role of Cisplatin in Inducing Acute Kidney Injury and Pyroptosis in Mice via the Exosome miR-122/ELAVL1 Regulatory Axis.

Although cisplatin is an effective chemotherapy drug for the treatment of various cancers, its clinical use is limited due to its side effects, especially nephrotoxicity. Unfortunately, acute kidney injury (AKI) caused by cisplatin remains one of the main challenges in effective cancer treatment. Evidence increasingly suggests that renal inflammation and pyroptotic inflammatory cell death of renal tubular epithelial cells (RTECs) mainly determine the progression and outcome of cisplatin-induced AKI. However, it is not clear how cisplatin regulates the pyroptosis of RTECs cells in AKI. The current study aimed to determine the regulation mechanism of AKI induced by cisplatin. We used cisplatin to induce AKI in vivo. We performed H&E staining of mouse kidney tissue sections and evaluated serological indicators of kidney injury (including blood urea nitrogen (BUN), serum creatinine, and tumor necrosis factor-alpha (TNF-alpha)). We used immunohistochemistry and western blot to detect the important substrate protein gasdermin D (GSDMD) and key target caspase-1 of pyroptosis, respectively. Cisplatin induced mouse AKI and RTECs pyroptosis. HK2 cell-derived exosomes treated with cisplatin influenced pyroptosis of the surrounding HK2 cells. Cisplatin-treated HK2 cells exosome-derived miR-122 regulated pyroptosis in the surrounding cells. Exosome-derived miR-122 affected cisplatin-induced AKI and HK2 cells pyroptosis by regulating the expression of embryonic lethal abnormal vision (ELAVL1). These results suggest that exosome miR-122 inhibited pyroptosis and AKI by targeting ELAVL1 under cisplatin treatment, and this offers a potential target for the treatment of AKI.

Lentiviral-mediated RNAi targeting caspase-3 inhibits apoptosis induced by serum deprivation in rat endplate chondrocytes in vitro

Current studies find that degenerated cartilage endplates (CEP) of vertebrae, with fewer diffusion areas, decrease nutrient supply and accelerate intervertebral disc degeneration. Many more apoptotic cells have been identified in degenerated than in normal endplates, and may be responsible for the degenerated grade. Previous findings suggest that inhibition of apoptosis is one possible approach to improve disc regeneration. It is postulated that inhibition of CEP cell apoptosis may be responsible for the regeneration of endplates. Caspase-3, involved in the execution phase of apoptosis, is a candidate for regulating the apoptotic process. In the present study, CEP cells were incubated in 1% fetal bovine serum. Activated caspases were detected to identify the apoptotic pathway, and apoptosis was quantified by flow cytometry. Lentiviral caspase-3 short hairpin RNA (shRNA) was employed to study its protective effects against serum deprivation. Silencing of caspase-3 expression was quantified by reverse transcription-polymerase chain reaction and Western blots, and inhibition of apoptosis was quantified by flow cytometry. Serum deprivation increased apoptosis of rat CEP cells through activation of a caspase cascade. Lentiviral caspase-3 shRNA was successfully transduced into CEP cells, and specifically silenced endogenous caspase-3 expression. Surviving cells were protected by the downregulation of caspase-3 expression and activation. Thus, lentiviral caspase-3 shRNA-mediated RNAi successfully silenced endogenous caspase-3 expression, preventing inappropriate or premature apoptosis.

High expression of the circadian gene mPer2 diminishes the radiosensitivity f NIH 3T3 cells

Period2 is a core circadian gene, which not only maintains the circadian rhythm of cells but also regulates some organic functions. We investigated the effects of mPeriod2 (mPer2) expression on radiosensitivity in normal mouse cells exposed to 60Co-γ-rays. NIH 3T3 cells were treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) to induce endogenous mPer2 expression or transfected with pcDNA3.1(+)-mPer2 and irradiated with 60Co-γ-rays, and then analyzed by several methods such as flow cytometry, colony formation assay, RT-PCR, and immunohistochemistry. Flow cytometry and colony formation assay revealed that irradiated NIH 3T3 cells expressing high levels of mPer2 showed a lower death rate (TPA: 24 h 4.3 percent vs 12 h 6.8 percent and control 9.4 percent; transfection: pcDNA3.1-mPer2 3.7 percent vs pcDNA3.1 11.3 percent and control 8.2 percent), more proliferation and clonogenic survival (TPA: 121.7 ± 6.51 vs 66.0 ± 3.51 and 67.7 ± 7.37; transfection: 121.7 ± 6.50 vs 65.3 ± 3.51 and 69.0 ± 4.58) both when treated with TPA and transfected with mPer2. RT-PCR analysis showed an increased expression of bax, bcl-2, p53, c-myc, mre11, and nbs1, and an increased proportionality of bcl-2/bax in the irradiated cells at peak mPer2 expression compared with cells at trough mPer2 expression and control cells. However, no significant difference in rad50 expression was observed among the three groups of cells. Immunohistochemistry also showed increased protein levels of P53, BAX and proliferating cell nuclear antigen in irradiated cells with peak mPer2 levels. Thus, high expression of the circadian gene mPer2 may reduce the radiosensitivity of NIH 3T3 cells. For this effect, mPer2 may directly or indirectly regulate the expressions of cell proliferation- and apoptosis-related genes and DNA repair-related genes.