Interaction analysis of RNA G-quadruplex with ligands and in situ imaging application.

RNA G4, as an integral branch of G4 structure, possesses distinct interactions with ligands compared to the common DNA G4, thus the investigation of RNA G4/ligand interactions might be considered as a fresh breakthrough to improve the biosensing performance of G4/ligand system. In this study, we comparatively explored the structural and functional mechanisms of RNA G4 and DNA G4 in the interaction with ligands, hemin and thioflavin T (ThT), utilizing the classical PS2.M sequence as a model. We found that although the catalytic performance of RNA G4/hemin system was lower than DNA G4/hemin, RNA G4/ThT fluorescence system exhibited a significant improvement (2∼3-fold) compared to DNA G4/ThT, and adenine modification could further enhance the signaling. Further, by exploring the interaction between RNA G4 and ThT, we deemed that RNA G4 and ThT were stacked in a bimolecular mode compared to single-molecule binding of DNA G4/ThT, thus more strongly limiting the structural spin in ThT excited state. Further, RNA G4/ThT displayed higher environmental tolerance and lower ion dependence than DNA G4/ThT. Finally, we employed RNA G4/ThT as a highly sensitive label-free fluorescent signal output system for in situ imaging of isoforms BCR-ABL e13a2 and e14a2. Overall, this study successfully screened a high-performance RNA G4 biosensing system through systematic RNA G4/ligands interaction studies, which was expected to provide a promising reference for subsequent G4/ligand research.

Poor nutritional status is associated with the severity of omicron infection in the older adults.

BACKGROUND: The Omicron wave of Coronavirus disease 2019 (COVID-19) remains the dominant strain worldwide. The studies of nutritional status in geriatric people with COVID-19 Omicron variant are limited. Thus, the aim of this study was to investigate the incidence of poor nutritional status among Omicron infected older patients, and to explore the correlation between the nutritional status and the severity of Omicron infection in older patients. METHODS: This is a retrospective cross-sectional study. According to the clinical symptoms, patients were divided into two groups: mild and moderate to severe. Mini Nutritional Assessment short-form (MNA-SF) was conducted when patients were admitted and poor nutritional status was defined as MNA-SF score of 0-11. The inflammatory markers including neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and systemic inflammatory index (SII) were calculated and compared between two groups. RESULTS: Total of 324 patients were enrolled, with median [interquartile range (IQR)] age of 73 (17) years. Overall, 241 cases were mild, 83 cases were moderate to severe at the time of diagnosis and that 54.3% of patients had poor nutritional status. Patients with poor nutritional status were found to be older (P < 0.001) and less vaccinated (P < 0.001), with a longer virus shedding duration (P = 0.022), more comorbidities (≥ 2) (P = 0.004) and higher value of NLR (P < 0.001), PLR (P < 0.001) and SII (P = 0.012). Vaccination, cycle threshold value in ORF1ab gene (OR CT value) and female, higher MNA-SF score was negatively connected with probability of moderate to severe infection. For every 1 score increase in MNA-SF, the odds ratio of moderate to severe infection decreased by 14.8% [adjusted odds ratio (aOR), 0.852; 95% confidence interval (CI): 0.734-0.988; P = 0.034]. CONCLUSIONS: Older patients with poor nutritional status are more likely to develop moderate to severe Omicron infection.

Result of a Pilot External Quality Assessment Scheme for Clinical Diagnosis of Inherited Metabolic Disorders in China.

BACKGROUND: We aimed to evaluate the diagnostic capabilities of Chinese laboratories for inherited metabolic disorders (IMDs) using gas chromatography-mass spectrometry (GC-MS) on urine samples. Meanwhile, based on the result of the pilot external quality assessment (EQA) scheme, we hope to establish a standardized and reliable procedure for future EQA practice. METHODS: We recruited laboratories that participated in the EQA of quantitative analysis of urinary organic acids with GC-MS before joining the surveys. In each survey, a set of five real urine samples was distributed to each participant. The participants should analyze the sample by GC-MS and report the "analytical result", "the most likely diagnosis", and "recommendation for further tests" to the NCCL before the deadline. RESULTS: A total of 21 laboratories participated in the scheme. The pass rates were 94.4% in 2020 and 89.5% in 2021. For all eight IMDs tested, the analytical proficiency rates ranged from 84.7% - 100%, and the interpretational performance rate ranged from 88.2% - 97.0%. The performance on hyperphenylalaninemia (HPA), 3-methylcrotonyl-CoA carboxylase deficiency (MCCD), and ethylmalonic encephalopathy (EE) samples were not satisfactory. CONCLUSIONS: In general, the participants of this pilot EQA scheme are equipped with the basic capability for qualitative organic acid analysis and interpretation of the results. Limited by the small size of laboratories and samples involved, this activity could not fully reflect the state of clinical practice of Chinese laboratories. NCCL will improve the EQA scheme and implement more EQA activities in the future.

The relationship between family resilience, post-traumatic growth, and caregiver burden among family caregivers of stroke survivors: a cross-sectional study.

The study aimed to explore the relationship between family resilience, post-traumatic growth(PTG), and caregiver burden among family caregivers of stroke survivors. Researchers conducted a cross-sectional study to recruit 253 family caregivers of stroke survivors from a public hospital in Shandong Province, China. Caregivers completed sociodemographic information, the Shortened Chinese Version of the Family Resilience Assessment Scale, the Post-traumatic Growth Inventory, and the Zarit Caregiver Burden Interview. We used Amos 24.0 to construct structural equation models and examine the mediating effects of stroke survivors' post-traumatic growth. Family resilience was positively associated with post-traumatic growth, and both family resilience and post-traumatic growth were negatively associated with caregiver burden. Post-traumatic growth partially mediated the relationship between family resilience and caregiver burden, and the mediating effect accounted for 21.27% of the total effect. Targeted interventions should address family resilience and post-traumatic growth as protective factors of caregiver burden.

Purinergic receptor P2X7 activates NOX2/JNK signaling to participate in granulosa cell inflammation and apoptosis in polycystic ovary syndrome.

Increasing evidence shows that polycystic ovary syndrome (PCOS) is often accompanied by an inflammatory response, hence, appropriately managing granulosa cell inflammation is critical to regaining ovarian function in PCOS. In this study, the differential levels of purinergic receptor P2X7 between the control and PCOS samples in the dataset GSE34526 were assessed, then PCOS mouse models were established. Following evaluating the fluctuations in hormone levels, inflammatory cytokines, and P2X7, mice received treatment with the P2X7 antagonist A740003. Its effects on hormones, inflammation, apoptosis, and NOX2 signaling in mice were examined. Afterward, primary mouse granulosa cells were isolated, and the mediating role of NOX2 signaling in the P2X7 regulatory pathway was confirmed by transfection of NOX2 overexpression plasmids. The results demonstrated that P2X7 was significantly elevated in the PCOS samples in the dataset. Compared with the control group, PCOS mice had significant differences in the follicle-stimulating hormone, luteinizing hormone, testosterone, anti-Müllerian hormone, inflammatory factors, and P2X7. Treatment with A740003 partially restored these parameter levels, including NOX2 signaling. Based on in vitro experiments on primary mouse granulosa cells, the above findings were re-verified, and the overexpression of NOX2 could reverse the regulatory function of P2X7. The present study highlights that P2X7 level increases in PCOS, and inhibition of P2X7 can reduce disease symptoms. It is involved in inflammation and apoptosis in granulosa cells through NOX2/JNK signaling.

Cytokine network imbalance in children with B-cell acute lymphoblastic leukemia at diagnosis.

Immune imbalance has been proved to be involved in the pathogenesis of hematologic neoplasm. However, little research has been reported altered cytokine network in childhood B-cell acute lymphoblastic leukemia (B-ALL) at diagnosis. Our study aimed to evaluate the cytokine network in peripheral blood of newly diagnosed pediatric patients with B-ALL. Serum levels of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF), interferon (IFN)-γ, and IL-17A in 45 children with B-ALL and 37 healthy control children were measured by cytometric bead array, while the level of transforming growth factor-ß1 (TGF-ß1) in the serum was measured by enzyme-linked immunosorbent assay. Patients showed a significant increase in IL-6 (p < 0.001), IL-10 (p < 0.001), IFN-γ (p = 0.023) and a significant reduction in TGF-ß1 (p = 0.001). The levels of IL-2, IL-4, TNF and IL-17A were similar in the two groups. Higher concentrations of pro-inflammatory cytokines were associated with febrile in patients without apparent infection by using unsupervised machine learning algorithms. In conclusion, our results indicated a critical role for aberrant cytokine expression profiles in the progression of childhood B-ALL. Distinct cytokine subgroups with different clinical features and immune response have been identified in patients with B-ALL at the time of diagnosis.

Analysis of Infectious Characteristics of Recurrent Vulvovaginal Candidiasis in Chengdu from 2018 to 2022.

BACKGROUND: The aim was to discover the infectivity characteristics of recurrent vulvovaginal candidiasis (RVVC) in Chengdu, Sichuan Province, and provide a reference for RVVC clinical diagnosis and treatment. METHODS: The clinical data of 500 patients with RVVC were retrospectively analyzed, including life history, clinical symptoms, combined gynecological diseases, age, and distribution of pathogenic fungi, and the in vitro drug sensitivity of isolated fungi to antifungal drugs was assessed. RESULTS: Among the 500 patients with RVVC, 486 (97.20%) had a sexual history, and the main clinical symptoms were vulva pruritus (394, 78.80%) and abnormal discharge (232, 46.40%). Common gynecological diseases were cervicitis (156 patients, 31.20%), human papillomavirus infection (130 patients, 26.00%), and coinfection with oth-er pathogens (127 patients, 25.40%). The high-incidence population was mainly concentrated in the 31 to 40-year-old age group, followed by the 20 to 30- and 41 to 50-year-old age groups. The number of patients gradually increased with time. Fungal culture was dominated by Candida albicans (69.80%), followed by Candida glabrata (28.40%), and Candida cerevisiae (0.60%). In vitro susceptibility testing showed that the highest drug resistance rate to antifungal drugs was to terbinafine (96.40%), followed by voriconazole (32.00%), fluconazole (26.40%), and itraconazole (17.40%), whereas the drug resistance rates to 5-fluorocytosine, caspofungin, amphotericin B, and micafungin were relatively low (1.80%, 0.60%, 0.40%, and 0.00%, respectively); the drug resistance rate to azoles gradually increased with age. CONCLUSIONS: The occurrence of RVVC is closely related to sexual history. The most common cases are in women of childbearing age aged 20 - 50. The main pathogen is C. albicans, and the resistance rate to common azole antifungal drugs is increasing over time.

Antibiotic Resistance of Hemophilus influenzae Isolated from Children in Southwest China.

BACKGROUND: Hemophilus influenzae (Hi) is one of the major pediatric bacterial pneumonia pathogens that heavily threatens children's lives and global health. With widespread usage as first-line treatment, the prevalence of ß-lactam-resistant strains is increasing sharply. In order to treat Hi more effectively, a systematic study on the antibiotic resistance profiles, ß-lactamase-negative ampicillin-resistant (BLNAR) strains isolation rate, and potential BLNAR resistance mechanism in our region is needed. METHODS: This study analyzed antimicrobial susceptibility of Hi, and clinical data of Hi-infected patients retrospectively. BLNAR and ß-lactamase-positive ampicillin-clavulanate resistant strains (BLPACR) were confirmed by the Kirby-Bauer method and ß-lactamase test. ftsI gene in BLNAR was sequenced to find out whether resistance was induced by penicillin-binding protein mutation. Ampicillin susceptibility test with or without efflux pump inhibitors were done to assess efflux pump contribution in BLNAR. RT-PCR was performed to evaluate the efflux pump genes' transcription levels. RESULTS: A total of 2,561 Hi strains were isolated in our hospital from January 2016 to December 2019. Male to female ratio was 1.52:1. Median age was 10 months. Infant (< 3 years old) infection accounted for 83.72%. Hi resistance rates to sulfamethoxazole-trimethoprim, ampicillin, cefathiamidine, cefaclor, cefuroxime, cephalothin, amoxicillin-clavulanate, tetracycline, chloramphenicol, ofloxacin, cefotaxime, and rifampin were 84.28%, 78.01%, 49.80%, 41.98%, 36.58%, 33.64%, 4.55%, 4.1%, 3.37%, 1.77%, 0.99%, and 0.12%, respectively, while 1.33% were BLNAR. BLNARs were classified into four groups by mutation patterns in ftsI gene and most strains were divided to Group Ⅲ/Ⅲ-like. EmrB, ydeA and norM transcription levels in some ampicillin-resistant strains were higher than their sensitive counterparts. CONCLUSIONS: Ampicillin is not sufficiently effective as a first-line Hi infection treatment. However, ampicillin-clavulanate and cefotaxime may be a better choice. Efflux pumps, emrB, ydeA and norM play roles in the high resistance to ampicillin.

Effects of Hemolysis on Routine Coagulation Tests when Tested on an Optical Coagulation Analyzer.

BACKGROUND: The Clinical and Laboratory Standards Institute recommends rejecting hemolyzed samples for coagulation tests. Sysmex CS5100 analyzer using an optical method is commonly used in laboratories. The influence of hemolysis on coagulation test has rarely been studied when tested on Sysmex CS5100. Determining this influence is necessary. METHODS: Freshly collected samples were artificially hemolyzed to simulate the hemolysis processes. Coagulation tests were conducted on a Sysmex CS5100 coagulation analyzer. Detection values before and after hemolysis were compared. RESULTS: The results showed that after hemolysis detection, the prothrombin time (PT) statistically decreased, while the partial thromboplastin time (APTT) statistically increased. There were no significant differences in fibrinogen (Fg), thrombin time (TT), D-dimer (DD) or fibrinogen degradation products (FDPs). Antithrombin activity was elevated in hemolyzed samples. CONCLUSIONS: Although differences in PT and APTT were statistically significant, there was no need for rejection of hemolyzed samples due to insufficient clinical effects when tested on Sysmex CS5100 analyzer. Falsely elevated AT result may lead to misdiagnosis in patients with severe diseases, which should be carefully considered.

Antinuclear Antibodies in Erythema Multiforme: Transient Occurrence During Acute Illness.

BACKGROUND: Children with target lesions are frequently diagnosed with erythema multiforme (EM). EM was not previously thought to be associated with any specific autoimmune serological abnormality. METHODS: We report the case of a 7-year-old girl who developed rashes all over her body with target shaped lesions. Based on clinical appearance and medical history, she was diagnosed with severe erythema multiforme and treated with methylprednisolone. Relevant laboratory tests were performed at admission. RESULTS: At the height of her infection, the antinuclear antibody (ANA) test showed a positive ANA with a titer of 1:100 (speckled pattern) and positive anti-SSA and anti-Ro-52 antibodies. Then she was adjusted for medication. After a week, the infection was relieved, and the re-examination was negative for ANA, anti-SSA, and anti-Ro-52 antibodies. CONCLUSIONS: In previously reported EM cases, ANA is generally not considered to be present. The disappearance of ANA during the convalescent phase suggests that ANA is expressed during the acute phase of EM infection. Its correlation with infection severity warrants further research on the mechanism of autoantibody formation in EM.

A Case Report of a Novel Isovaleryl-CoA Dehydrogenase Gene Mutation in a Chinese Family with Isovaleric Acidemia.

BACKGROUND: Isovaleric acidemia (IVA) is a rare autosomal-recessive metabolic disorder caused by a genetic deficiency of isovaleryl-CoA dehydrogenase (IVD). Deficiency of IVD leads to the accumulation of organic acids; however, the genotype-phenotype relationship has not been well established. METHODS: Two brothers with acute neonatal IVA in a Chinese family were reported, and their clinical manifestations and examination were described. MS/MS and GCMS were used to perform organic acid analysis of blood samples and urine samples, and the patient's blood was sequenced by NGS and Sanger sequencing of the ivd gene. RESULTS: Sequence analysis of the ivd gene identified compound heterozygous mutations in the patient, the c.250T>C (p.W84R) missense mutation (novel) and the c.466-3_466-2 delCAinsGG splicing mutation, which were inherited from their parents. Various bioinformatics prediction algorithms suggest that the p.W84R missense mutation may destabilize the IVD monomer and reduce its ability to bind to substrates. CONCLUSIONS: Both the clinical and genetic features of this family will help us to further expand the knowledge of IVA.

SIRT6 reduces the symptoms of premature ovarian failure and alleviates oxidative stress and apoptosis in granulosa cells by degrading p66SHC via H3K9AC.

CONTEXT: Substantial evidence suggests that ovarian oxidative stress can result in severe ovarian dysfunction. OBJECTIVE: The purpose of this article is to investigate the potential of SIRT6 in alleviating premature ovarian failure (POF) by inhibiting oxidative stress. METHODS: To mimic POF, mice were administered daily subcutaneous injections of d-galactose. The levels of E2, FSH, LH, AMH, and progesterone in serum were measured, along with changes in follicles and SIRT6 levels. Mice were treated with the SIRT6 agonist MDL-800, SIRT6 levels, follicles, and aforementioned hormones were reassessed. The effects of MDL-800 on oxidative stress and apoptosis were subsequently identified. Primary granulosa cells were isolated from mice, and the effects of H2O2 and MDL-800 on cell viability, oxidative stress, SIRT6 level, and apoptosis were evaluated. In addition, the regulation of SIRT6 on H3K9AC/p66SHC was verified by examining changes in protein levels, promoter activity, and the reversal effects of p66SHC overexpression. RESULTS: MDL-800 mitigated hormone fluctuations, reduced follicle depletion in ovarian tissue, and attenuated oxidative stress and apoptosis in mice. In vitro experiments demonstrated that MDL-800 enhanced the resilience of primary granulosa cells against H2O2, as evidenced by increased cell viability and reduced oxidative stress and apoptosis. Furthermore, SIRT6 was found to decrease H3K9AC and p66SHC levels, as well as attenuate p66SHC promoter activity. The protective effects of MDL-800 on cells were reversed upon p66SHC overexpression. CONCLUSION: In summary, this study highlights that activation of SIRT6 can alleviate POF and reduce oxidative stress by degrading H3K9AC and suppressing p66Shc levels in granulosa cells.

Relationship between Body Mass Index and Bone Turnover Markers in Girls with Idiopathic Central Precocious Puberty.

Background: This study aimed to determine the effect of body mass index (BMI) on bone turnover markers in girls with idiopathic central precocious puberty (ICPP) according to weight status at diagnosis. Methods: Two hundred and eleven girls with ICPP were divided according to their weight status at diagnosis into three groups: normal weight, overweight, and obese. The serum levels of total procollagen type 1 N-terminal propeptide (P1NP), N-terminal midfragment of osteocalcin, ß-C-terminal telopeptide of type 1 collagen, and some biochemical indicators were measured. Associations between variables were evaluated by multiple regression analysis. Results: Serum P1NP concentrations were significantly different among groups (p < 0.001). No other significant differences were noted in N-terminal midfragment of osteocalcin and ß-C-terminal telopeptide of type 1 collagen. BMI was associated with estradiol (r = 0.155, p < 0.05) and inversely associated with P1NP (r = -0.251, p < 0.01), luteinizing hormone peak (r = -0.334, p < 0.01), follicle-stimulating hormone peak (r = -0.215, p < 0.01), and luteinizing hormone/follicle-stimulating hormone peak (r = -0.284, p < 0.01). Multiple regression analysis of factors associated with BMI showed that it was correlated with P1NP, follicle-stimulating hormone base, and luteinizing hormone peak in the overweight group and the obese group. Conclusions: Our findings showed that BMI was associated with P1NP, revealing the reduction of bone formation in overweight and obese girls with ICPP. During the diagnosis and treatment of girls with ICPP, attention should be paid to body weight and bone metabolism.

Advances in the Anti-Tumor Activity of Biflavonoids in Selaginella.

Despite the many strategies employed to slow the spread of cancer, the development of new anti-tumor drugs and the minimization of side effects have been major research hotspots in the anti-tumor field. Natural drugs are a huge treasure trove of drug development, and they have been widely used in the clinic as anti-tumor drugs. Selaginella species in the family Selaginellaceae are widely distributed worldwide, and they have been well-documented in clinical practice for the prevention and treatment of cancer. Biflavonoids are the main active ingredients in Selaginella, and they have good biological and anti-tumor activities, which warrant extensive research. The promise of biflavonoids from Selaginella (SFB) in the field of cancer therapy is being realized thanks to new research that offers insights into the multi-targeting therapeutic mechanisms and key signaling pathways. The pharmacological effects of SFB against various cancers in vitro and in vivo are reviewed in this review. In addition, the types and characteristics of biflavonoid structures are described in detail; we also provide a brief summary of the efforts to develop drug delivery systems or combinations to enhance the bioavailability of SFB monomers. In conclusion, SFB species have great potential to be developed as adjuvant or even primary therapeutic agents for cancer, with promising applications.

Analysis of Ureaplasma urealyticum, Chlamydia trachomatis, Mycoplasma genitalium and Neisseria gonorrhoeae infections among obstetrics and gynecological outpatients in southwest China: a retrospective study.

BACKGROUND: The aim of this study was to analyze the present situation of Ureaplasma urealyticum (UU), Chlamydia trachomatis (CT), Mycoplasma genitalium (MG) and Neisseria gonorrhoeae (NG) infections among obstetrics and gynecological outpatients in southwest China. METHODS: A total of 3225 urogenital swabs were included in this study. All swabs were tested by RNA-based simultaneous amplification and testing (SAT) methods. Routine analysis of leucorrhea smear and drug susceptibility were performed in UU positive patients. RESULTS: Of these 3225 outpatients, the positive rate was 27.07% for UU, 4.99% for CT, 3.10% for MG, and 0.09% for NG. UU, CT, and MG infections were more common in women of reproductive age (aged 25-34 years), while NG infection was more prominent in women aged 30-34 years and over 40 years. Overall, the infection rate of UU was significantly higher than that of the other three infections, and UU also played a major role even in the mixed infections. 65.07% of the UU positive patients had negative results on routine leucorrhea smear analysis, and the remaining patients may have bacterial vaginitis (15.79%), fungal vaginitis (11.48%), trichomonas vaginitis (0.96%) or other vaginal inflammation (6.70%). We have observed that maternal UU infection can lead to low birth weight, neonatal pneumonia, and premature delivery. The results of the drug susceptibility test of UU showed a higher sensitivity to pristinamycin, doxycycline, tetracycline, clarithromycin, and josamycin (100%, 97.0%, 96.4%, 95.9%, and 95.3%, respectively), and lower sensitivity to ciprofloxacin and ofloxacin (2.4% and 4.7% respectively). CONCLUSIONS: This study could contribute to a better understanding of the current epidemiological features of UU, CT, MG, and NG among obstetrics and gynecological outpatients in southwest China, and thus facilitate to development of the more effective intervention, prevention, and treatment of reproductive tract infection.

Age and sex specific reference intervals of 13 hematological analytes in Chinese children and adolescents aged from 28 days up to 20 years: the PRINCE study.

OBJECTIVES: Pediatric Reference Intervals in China (PRINCE) is a nationwide initiative that aims to establish and validate harmonized reference intervals (RIs) for Chinese children and adolescents, in which 15,150 healthy volunteers aged up to 20 years were recruited from 11 centers to establish RIs and 7,557 children and adolescents were enrolled from 21 centers to validate RIs. METHODS: The complete blood cell counts (CBC) of venous whole blood were measured by hematology analyzers through Sysmex systems in different centers. Age- and sex-specific RIs were calculated according to the guidelines. RESULTS: Unlike adults with certain levels of analyte concentrations, hematological parameters of children changed through growth and development. Red blood cell counts, hemoglobin, and hematocrit increased with age, and revealed higher concentrations in boys than girls after puberty. White blood cell counts and platelet counts showed significant higher levels than adults before 2 years of age, and then gradually decreased without distinct sex differences. In addition, lymphocyte counts decreased with age while neutrophil counts showed an opposite trend. The lower and upper limits of pediatric RIs of CBC were different from those of adults. CONCLUSIONS: The validation of RIs indicated that the PRINCE study provided a version of RIs suitable for most of regions in China. This first harmonized pediatric RIs of CBC across China provided a robust database to understand the dynamic changes of hematologic parameters from birth to adolescence, and will contribute to clinical diagnosis and prognosis evaluation for pediatric patients as well.

Reference intervals of 14 biochemical markers for children and adolescence in China: the PRINCE study.

OBJECTIVES: The Pediatric Reference Intervals in China (PRINCE) was initiated to establish the reference intervals (RIs) of Chinese children, as well as to make it possible to compare the variability of biochemical markers among countries internationally. METHODS: Healthy participants, aged up to 20 years, from 11 provinces across China, were enrolled in PRINCE and according to a standard screening procedure, that included a questionnaire survey, physical examinations and laboratory tests. Fasting venous blood specimens were collected. All serum specimens were analyzed with Cobas C702 in the center laboratory, i.e. clinical laboratory of Beijing Children's Hospital, with certified qualification (ISO15189). The nonparametric method recommended by Clinical Laboratory Standards Institute guidelines, was used to calculate the age- and sex-specified RIs. RESULTS: Among the 15,150 participants enrolled, 12,352 children (6,093 males and 6,259 females) were included to calculate RIs. The RIs for total protein, albumin, globulin, calcium, phosphate, potassium, sodium, chlorine, alkaline phosphatase, γ-glutamyl transpeptadase, alanine aminotransferase, aspartate aminotransferase, creatinine and urea were established by age- or sex-partitions. Most biochemical markers displayed larger variability and higher dispersion during the periods between 28 days and 1 year old, and included 4-6 age partitions commonly during 1 to <20 years old. In addition, differences of RIs between sexes usually occurs around the initiation of puberty at 12-13 years old. CONCLUSIONS: The age- and sex-specified RIs of 14 biochemical markers in PRINCE study can provide a solid reference, which will be transferred into relevant RIs for other clinical laboratory's platforms according to the CLSI guidelines.

Longer Time Intervals From Symptom Onset to Diagnosis Affect the Overall Survival in Children With Acute Lymphoblastic Leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Early diagnosis and timely treatment are essential for effective cancer control and have been widely analyzed in childhood cancer. However, few studies have described the time to diagnosis and treatment in children with ALL. This study investigated delays in diagnosis and treatment initiation and their impact on survival. METHODS: This retrospective cohort study included 419 patients 0 to 14 years old at a tertiary hospital between 2011 and 2015. The optimal cutoff values for delays were determined by X-tile software. The Kaplan-Meier method and Cox regression models were used to evaluate the impact of delays on survival. RESULTS: The median diagnosis, treatment, and total delays were 21 (interquartile range [IQR]: 11-35), 4 (IQR: 2-7), and 26 (IQR: 16-43) days, respectively. The results of multivariate analyses showed that diagnosis delay, risk stratification, and minimal residual disease level were independent predictors for treatment outcome in childhood ALL. CONCLUSIONS: These findings suggested that a longer time to diagnosis negatively affected the clinical outcome of childhood ALL. Reducing the time to diagnosis could help to improve survival in these patients.

The Interaction between Vitamin D and Diets on Serum Lipids in Chinese Han Adolescents.

BACKGROUND: Abnormal serum lipids are closely related to cardiovascular disease. Recent studies have shown that vitamin D (VD) and vitamin D receptor (VDR) FokI polymorphism as well as dietary pattern are involved in regulating serum lipids. METHODS: According to diet pattern, adolescents were divided into high-carbohydrate (high-CHO) and non-high-carbohydrate (non-high-CHO) diet group. Based on VDR FokI polymorphism, they were assigned into TT genotype and C allele carriers. Serum lipids, glucose, and 25-hydroxyvitamin D [25(OH)D] were measured. A linear regression model was established and analyzed. RESULTS: Subjects in the non-high-CHO diet group had higher glucose than those in the high-CHO diet group. With the increasing of VD, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), cholesterol/high density lipoprotein cholesterol (TC/HDL-C), LDL-C/HDL-C decreased. TT genotype subjects had higher TC and HDL-C compared with C allele carriers. As for log triglycerides (TG), TC/HDL-C, logTG/HDL-C, there were interactions between the level of VD and diet pattern. Under the low VD level, subjects in the high-CHO diet group had higher logTG and logTG/HDL-C compared with those in the non-high-CHO diet group. However, under the medium and high level of VD, the results were opposite. In addition, under the low and medium level of VD, subjects in the high-CHO diet group had higher TC/HDL-C. CONCLUSIONS: Serum lipids are not only affected by vitamin D, VDR FokI polymorphism and dietary pattern, but also interrelated as well. The impact of diet pattern on lipids may be reversed by the high level of serum VD.

Analysis of Aeroallergens in Sichuan Province after the COVID-19 Epidemic.

BACKGROUND: Identifying the distribution and pattern of specific aeroallergens in Sichuan, China, after the corona-virus disease (COVID-19) epidemic and to provide a basis for future prevention and clinical treatment. METHODS: Serological tests for 10 types of aeroallergens were performed on 10,036 participants attending the West China Second University Hospital from January 2020 to January 2021. SPSS23.0 was used to statistically analyze their specific immunoglobulin E (sIgE) grades in different genders, various age groups, and different diseases. RESULTS: Of the 10,036 participants, 4,578 (45.62%) were allergic to at least one allergen. House dust had the highest sensitization rate (2,974, 29.63%), followed by Dermatophagoides farina (2,717, 27.07%) and Dermatophagoides pteronyssinus (2,611, 26.02%). Male and female participants had no significant difference in overall sensitization distributions. The prevalence differences between 0 - 3, 4 - 6, 7 - 9, 10 - 12, 13 - 15, and over 16-year-old age groups were statistically significant (p < 0.05), and the highest incidence age for children to be sensitive to aeroallergens was 4 - 6 years, respectively. Sensitization to D. pteronyssinus, D. farina, house dust, dog epithelium, and Alternaria alternata was more common in patients with rhinitis and asthma compared with bronchitis. CONCLUSIONS: Aeroallergens are important causes of respiratory-related allergic diseases, and the characteristics of allergen sensitization discovered in this study could help with inhalant allergy disease prevention, diagnosis, and management in the post-epidemic era.