COVID-19 in the Tibet, China, the roof of the world: a comparative analysis of high-altitude residents and newcomers.

BACKGROUND: After a 920-day hiatus, COVID-19 resurged in the Tibet Autonomous Region of China in August 2022. This study compares the characteristics of COVID-19 between high-altitude residents and newcomers, as well as between newcomers and lowlanders. METHODS: This multi-center cohort study conducted at the Third People's Hospital of Tibet Autonomous Region and Beijing University Shenzhen Hospital, included 520 high-altitude resident patients, 53 high-altitude newcomer patients, and 265 lowlander patients infected with the Omicron variant. Initially, we documented epidemiological, clinical, and treatment data across varying residency at admission. We compared the severity of COVID-19 and various laboratory indicators, including hemoglobin concentration and SpO2%, over a 14-day period from the date of the first positive nucleic acid test, as well as the differences in treatment methods and disease outcomes between highlanders and high-altitude newcomers. We also compared several characteristics of COVID-19 between high-altitude newcomers and lowlanders. Univariate analysis, multivariable logistic regression, and the generalized linear mixed model were utilized for the analysis. RESULTS: No fatalities were observed. The study found no significant differences in COVID-19 severity or in the physiological measures of hemoglobin concentration and SpO2% between high-altitude and lowland residents. Similarly, there were no statistically significant differences in the values or trends of hemoglobin and SpO2% between high-altitude residents and newcomers throughout the 14-day observation period. However, compared to age- and sex-matched lowlander patients (1:5 ratio), high-altitude newcomers exhibited higher heart rates, respiratory rates, and average hemoglobin concentrations, along with lower platelet counts. There were no significant differences in hospital stays between the two groups. CONCLUSIONS: High-altitude residents and newcomer patients exhibit clinical similarities. However, the clinical characteristics of high-altitude newcomers and lowlander patients differ due to the impact of the high-altitude environment. These results highlight potential considerations for public health strategies in high-altitude regions such as Tibet.

Maternal and fetal risk factors for congenital anomalies of the kidney and urinary tract: a birth cohort study in urban China.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are among the most common causes of kidney diseases in children. Previous studies on CAKUT etiologies have been predominantly focused on non-modifiable genetic risk factors. The existing nongenetic studies are limited by lack of comprehensive investigation of potentially modifiable risk factors and the inability to distinguish among various phenotypes of CAKUT. Therefore, this study aimed to comprehensively evaluate both maternal and fetal risk factors of CAKUT, sorted by disease phenotype. METHODS: A prospective birth cohort study was conducted among 10,179 women who delivered a singleton live newborn in Lanzhou, China, between 2010 and 2012. Face-to-face interviews were conducted among the participants within 1-3 days after delivery using standard questionnaires to collect information on maternal demographics and characteristics. All newborns underwent postnatal renal ultrasonographic screening during their routine 1-month checkup. Clinical data, including birth outcomes and maternal complications, were confirmed by reviewing their medical records. Maternal and fetal risk factors were compared in children with and without CAKUT. Multivariable logistic regression analysis was performed to identify independent risk factors of CAKUT and their phenotypes, respectively. RESULTS: A total of 489 (4.8%) cases of CAKUT were identified. Logistic regression revealed that maternal overweight (pre-pregnancy), gestational diabetes, preterm birth, and low birth weight were independent risk factors for CAKUT. Maternal overweight increased the risk of vesicoureteral reflux (VUR, odds ratio (OR) = 1.441, 95% confidence interval (CI) 1.010-2.057) and posterior urethral valves (PUV, OR = 1.868, 95% CI 1.074-3.249). Gestational diabetes increased the risk of ureteropelvic junction obstruction (UPJO, OR = 1.269; 95% CI 1.044-1.543) and posterior urethral valves (OR = 1.794; 95% CI 1.302-2.474). Preterm birth increased the risk of ureteropelvic junction obstruction (OR = 1.056; 95% CI 1.004-1.111). CONCLUSIONS: Our study identified various risk factors associated with different CAKUT phenotypes, stressing the importance of separate analyses for each phenotype. Our findings may provide helpful guidance on developing targeted and effective CAKUT prevention programs in the future.

Noninvasive Prenatal Genetic Screening of Cell-Free Fetal DNA for Early Prediction of ß-Thalassemia Using Fiber Optic Nanogold-Linked Sorbent Assay.

ß-Thalassemia is a prevalent type of severe inherited chronic anemia, primarily identified in developing countries. The identification of single nucleotide polymorphisms (SNPs) plays a vital role in the early diagnosis of genetic diseases. Here, we reported the development of an amplification-free fiber optic nanogold-linked sorbent assay method using a fiber optic particle plasmon resonance (FOPPR) biosensor for rapid and ultrasensitive detection of SNPs. Herein, MutS protein was selected as the biorecognition capture probe and immobilized on the sensing region to capture the target mutant DNA, which was hybridized with a single-base mismatched single-stranded DNA labeled by a gold nanoparticle (AuNP). The AuNP acts as a signaling agent to be detected by the FOPPR biosensor when it is bound on the fiber core surface. The method effectively differentiates mismatched double-stranded DNA by MutS protein from perfectly matched/complementary dsDNA. It exhibits an impressively low detection limit for the detection of SNPs at approximately 10-16 M using low-cost sensor chips and devices. By determination of the ratio of mutant DNA to normal DNA in cell-free genomic DNA from blood samples, this method is promising for diagnosing ß-thalassemia in fetuses without invasive testing techniques.

PRMT6-mediated ADMA promotes p62 phase separation to form a negative feedback loop in ferroptosis.

Purpose: Due to intrinsic defensive response, ferroptosis-activating targeted therapy fails to achieve satisfactory clinical benefits. Though p62-Keap1-Nrf2 axis is activated to form a negative feedback loop during ferroptosis induction, how p62 is activated remains largely unknown. Methods: MTS assay was applied to measure cell growth. Lipid ROS was detected with C11-BODIPY reagent by flow cytometer. Quantitative real-time PCR (qPCR) and western blotting were performed to determine mRNA and protein level. Immunofluorescence (IF) was performed to examine the distribution of proteins. Fluorescence recovery after photobleaching (FRAP) was adopted to evaluate p62 phase separation. Immunoprecipitation (IP), co-IP and Proximal ligation assay (PLA) were performed to detected protein posttranslational modifications and protein-protein interactions. Tumor xenograft model was employed to inspect in vivo growth of pancreatic cancer cells. Results: Upon ferroptosis induction, Nuclear Factor E2 Related Factor 2 (Nrf2) protein and its downstream genes such as HMOX1 and NQO1 were upregulated. Knockdown of p62 significantly reversed Nrf2 upregulation and Keap1 decrease after ferroptosis induction. Knockdown of either p62 or Nrf2 remarkably sensitized ferroptosis induction. Due to augmented p62 phase separation, formation of p62 bodies were increased to recruit Keap1 after ferroptosis induction. Protein arginine methyltransferase 6 (PRMT6) mediated asymmetric dimethylarginine (ADMA) of p62 to increase its oligomerization, promoting p62 phase separation and p62 body formation. Knockdown of p62 or PRMT6 notably sensitized pancreatic cancer cells to ferroptosis both in vitro and in vivo through suppressing Nrf2 signaling. Conclusion: During ferroptosis induction, PRMT6 mediated p62 ADMA to promote its phase separation, sequestering Keap1 to activate Nrf2 signaling and inhibit ferroptosis. Therefore, targeting PRMT6-mediated p62 ADMA could be a new option to sensitize ferroptosis for cancer treatment.

The regulation and function of Nrf2 signaling in ferroptosis-activated cancer therapy.

Ferroptosis is an iron-dependent programmed cell death process that involves lipid oxidation via the Fenton reaction to produce lipid peroxides, causing disruption of the lipid bilayer, which is essential for cellular survival. Ferroptosis has been implicated in the occurrence and treatment response of various types of cancer, and targeting ferroptosis has emerged as a promising strategy for cancer therapy. However, cancer cells can escape cellular ferroptosis by activating or remodeling various signaling pathways, including oxidative stress pathways, thereby limiting the efficacy of ferroptosis-activating targeted therapy. The key anti-oxidative transcription factor, nuclear factor E2 related factor 2 (Nrf2 or NFE2L2), plays a dominant role in defense machinery by reprogramming the iron, intermediate, and glutathione peroxidase 4 (GPX4)-related network and the antioxidant system to attenuate ferroptosis. In this review, we summarize the recent advances in the regulation and function of Nrf2 signaling in ferroptosis-activated cancer therapy and explore the prospect of combining Nrf2 inhibitors and ferroptosis inducers as a promising cancer treatment strategy.

Sivelestat Inhibits Vascular Endothelial Injury Induced by Inflammatory Response and Improves the Prognosis of Hemorrhagic Fever with Renal Syndrome in Children: An Ambispective Cohort Study.

Background: In Asia, Hanta virus (HTNV) results in severe hemorrhagic fever with renal syndrome (HFRS). The efficacy of sivelestat in treating children with HTNV-induced HFRS remains unclear. Methods: An ambispective cohort study was performed on children diagnosed with HFRS and hospitalized at the Children's Hospital Affiliated to Xi'an Jiaotong University from August 2018 to 2023. Patients who received neutrophil elastin-inhibitor infusion between August 2019 and August 2023 were assigned to the sivelestat group, while patients who did not were assigned to the control group. The independent sample t test was used for inter-group analysis. The Chi-square test and Fisher's exact probability test were used for categorical variables. Spearman correlation test was used to evaluate the correlation between two sets of continuous variables. Kaplan-Meier survival curve and Log -Rank test was used to evaluate the difference in cumulative probability of survival between the two groups. Results: No significant differences were observed between the two groups in gender, age, contact history, body mass index, HFRS severity, clinical indexes at admission. Compared to the control group, the sivelestat group exhibited a significant decrease in the interleukin-8 level at 48 h (28.5±3 vs 34.5±3.5) and 72 h (21.3±4.5 vs 31.5±5.6) (P<0.05), as well as the ICAM-1 level at 48 h (553±122 vs 784±187) and 72 h (452±130 vs 623±85) (P<0.05). The concentration of VCAM-1 in the sivelestat group exhibited a consistent downward trend. Moreover, the level of VCAM-1 was significantly lower than that in the control group at 24 h (1760±289 vs 2180±445), 48 h (1450±441 vs 1890±267), and 72 h (1149±338 vs 1500±396) (P<0.05). Kaplan-Meier curve analysis revealed a statistically significant difference in the cumulative probability of survival between two groups (P = 0.041). In the secondary outcomes, the sivelestat group demonstrated a decrease in the utilization rate of mechanical ventilation and continuous renal replacement therapy (CRRT). Conclusion: Sivelestat may suppress neutrophil-mediated inflammatory response to reduce endothelial and organ damage, and improve clinical outcomes in children with severe hemorrhagic fever and renal syndrome.

Predicting prognosis and immunotherapy response in colorectal cancer by pericytes insights from single-cell RNA sequencing.

Immunotherapy has revolutionized the treatment of tumors, but there are still a large number of patients who do not benefit from immunotherapy. Pericytes play an important role in remodeling the immune microenvironment. However, how pericytes affect the prognosis and treatment resistance of tumors is still unknown. This study jointly analyzed single-cell RNA sequencing (scRNA-seq) data and bulk RNA sequencing data of multiple cancers to reveal pericyte function in the colorectal cancer microenvironment. Analyzing over 800 000 cells, it was found that colorectal cancer had more pericyte enrichment in tumor tissues than other cancers. We then combined the TCGA database with multiple public datasets and enrolled more than 1000 samples, finding that pericyte may be closely related to poor prognosis due to the higher epithelial-mesenchymal transition (EMT) and hypoxic characteristics. At the same time, patients with more pericytes have higher immune checkpoint molecule expressions and lower immune cell infiltration. Finally, the contributions of pericyte in poor treatment response have been demonstrated in multiple immunotherapy datasets (n = 453). All of these observations suggest that pericyte can be used as a potential biomarker to predict patient disease progression and immunotherapy response.

A portable, integrated microfluidics for rapid and sensitive diagnosis of Streptococcus agalactiae in resource-limited environments.

Streptococcus agalactiae (Group B Streptococcus, GBS) has been the leading cause of infections in newborns. Rapid and accurate diagnosis of GBS in pregnant women is a deterministic strategy to prevent newborn infection. Conventional detection methods based on nucleic acid amplification assay have been applied in GBS diagnosis in central laboratories, with demonstrated high sensitivity. However, their heavy dependence on instrumentation and trained technicians forms remarkable obstacles to GBS detection in wide scenarios, including self-testing, and bedside-/community-screening. Furthermore, the structures of GBS bring about extra challenges to the nucleic acid extraction and purification. Novel GBS diagnosis platforms integrating sample processing, amplification, and read-out, are highly desired in clinical. Here, we report a portable, integrated microfluidics that enables rapid extraction of DNA from sampling swabs (<10 min), power-free DNA amplification (<30 min), and simple read-out in GBS detection. The platform works without an external pump, achieving rapid and highly efficient DNA extraction from clinical samples, with a significantly reduced time from 6 h to less than 50 min. Systematic clinical tests based on 47 patient samples validated the high performance of the platform, highlighted with a low limit of detection (LOD, 103 copies/ml), high sensitivity (100%), and specificity (100%). Head-to-head comparisons showed that the device improved the LOD by an order of magnitude than the traditional PCR method, showing a simple yet powerful POCT platform for home-/community-based testing towards GBS (and other pathogens) prevention in remote areas.

Role of lncRNAs in the pathogenesis of sepsis and their clinical significance.

Sepsis is a fatal organ dysfunction caused by the host's uncontrolled response to infection, with high morbidity and mortality. Early diagnosis and intervention are the most effective methods to reduce the mortality due to sepsis. However, there is still a lack of definite biomarkers or intervention targets for the diagnosis, evaluation, prognosis, and treatment of sepsis. Long non-coding RNAs (lncRNAs) are a type of non-coding transcript with a length ranging from 200 to 100,000 nucleotides. LncRNAs mainly locate in the cytoplasm and nucleus and participate in various signaling pathways related to inflammatory reactions and organ dysfunction. Recent studies have reported that lncRNAs are involved in regulating the pathophysiological process of sepsis. Some classical lncRNAs have been confirmed as promising biomarkers to evaluate the severity and prognosis of sepsis. This review summarizes the mechanical studies on lncRNAs in sepsis-induced acute lung, kidney, myocardial, and liver injuries, analyzes the role of lncRNAs in the pathogenesis of sepsis, and explores the possibility of lncRNAs as potential biomarkers and intervention targets for sepsis-induced multiple organ dysfunction.

Ferroptosis inducers enhanced cuproptosis induced by copper ionophores in primary liver cancer.

INTRODUCTION: Cuproptosis and ferroptosis are the two newly defined metal-related regulated cell death. However, the crosstalk between cuproptosis and ferroptosis is obscure. MATERIALS AND METHODS: We analyzed the effect of ferroptosis inducers on copper ionophores-induced cell death through CCK-8 assay. Cuproptosis was studied using immunofluorescence and protein soluble-insoluble fraction isolation. GSH assay, qRT-PCR and western blot were adopted to explore the machinery of ferroptosis inducers enhanced cuproptosis. And mouse xenograft model was built to detect the synergy effect of elesclomol-Cu and sorafenib in vivo. RESULTS: Herein we found that ferroptosis inducers sorafenib and erastin could enhance cuproptosis in primary liver cancer cells by increasing copper dependent lipoylated protein aggregation. Mechanically, sorafenib and erastin upregulated protein lipoylation via suppressing mitochondrial matrix-related proteases mediated ferredoxin 1 (FDX1) protein degradation, and reduced intracellular copper chelator glutathione (GSH) synthesis through inhibiting cystine importing. DISCUSSION/CONCLUSION: Our findings proposed that combination of ferroptosis inducers and copper ionophores to co-targeting ferroptosis and cuproptosis could be a novel therapeutic strategy for primary liver cancer.

Meta-Analysis of Cardiovascular Risk Factors in Offspring of Preeclampsia Pregnancies.

This study aimed to assess cardiovascular risk factors in the offspring of preeclampsia (PE) pregnancies. PubMed, Web of Science, Ovid, and other foreign language databases, as well as SinoMed, China National Knowledge Infrastructure, Wanfang, and China Science and Technology Journal Databases, were searched. The case-control studies on cardiovascular risk factors in the offspring of PE pregnancies from 1 January 2010 to 31 December 2019 were collected. A random-effects model or a fixed-effects model was used, and RevMan 5.3 software was used for meta-analysis to determine the OR value and 95%CI of each cardiovascular risk factor. A total of 16 documents were included in this research, all of which were case-control studies, with a total of 4046 cases in the experimental group and 31,505 in the control group. The meta-analysis that was conducted demonstrated that SBP [MD = 1.51, 95%CI (1.15, 1.88)] and DBP [MD = 1.90, 95%CI (1.69, 2.10)] values in the PE pregnancy offspring group presented an elevation relative to the non-PE pregnancy offspring group. The total cholesterol value in the PE pregnancy offspring group presented an elevation relative to the non-PE pregnancy offspring group [MD = 0.11, 95%CI (0.08, 0.13)]. The low-density lipoprotein cholesterol value in the PE pregnancy offspring group was comparable to that in the non-PE pregnancy offspring group [MD = 0.01, 95%CI (-0.02, 0.05)]. The high-density lipoprotein cholesterol value in the PE pregnancy offspring group presented an elevation relative to the non-PE pregnancy offspring group [MD = 0.02, 95%CI (0.01, 0.03)]. The non-HDL cholesterol value in the PE pregnancy offspring group presented an elevation relative to the non-PE pregnancy offspring group [MD = 0.16, 95%CI (0.13, 0.19)]. The triglycerides [MD = -0.02, 95%CI (-0.03, -0.01)] and glucose [MD = -0.08, 95%CI (-0.09, -0.07)] values in the PE pregnancy offspring group presented a depletion relative to the non-PE pregnancy group. The insulin value in the PE pregnancy offspring group presented a depletion relative to the non-PE pregnancy offspring group [MD = -0.21, 95%CI (-0.32, -0.09)]. The BMI value in the PE pregnancy offspring group presented an elevation relative to the non-PE pregnancy offspring group [MD = 0.42, 95%CI (0.27, 0.57)]. In conclusion, dyslipidemia, elevated blood pressure, and increased BMI occur postpartum with PE, all of which are risk factors for cardiovascular diseases.

A new formula based on height for determining endotracheal intubation depth in pediatrics: A prospective study.

STUDY OBJECTIVE: The main objective was to devise an endotracheal intubation formula based on pediatric patients' strongly correlated growth parameters. The secondary objective was to compare the accuracy of the new formula to the age-based formula from Advanced Pediatric Life Support Course (APLS formula) and the middle finger length-based formula (MFL-based formula). DESIGN: A prospective, observational study. SETTING: Operation. PATIENTS: 111 subjects age 4-12 years old undergoing elective surgeries with general orotracheal anesthesia. INTERVENTIONS AND MEASUREMENTS: Growth parameters, including age, gender, height, weight, BMI, middle finger length, nasal-tragus length, and sternum length, were measured before surgeries. Tracheal length and the optimal endotracheal intubation depth (D) were measured and calculated by Disposcope. Regression analysis were used to establish a new formula for predicting the intubation depth. A self-controlled paired design was used to compare the accuracy of the intubation depth between the new formula, APLS formula, and MFL-based formula. MAIN RESULTS: Height (R = 0.897, P < 0.001) was strongly correlated to tracheal length and the endotracheal intubation depth in pediatric patients. New formulae basing on height were established, including new formula 1: D (cm) = 4 + 0.1 × Height (cm) and new formula 2: D (cm) = 3 + 0.1 × Height (cm). Via Bland-Altman analysis, the mean differences for new formula 1, new formula 2, APLS formula and MFL-based formula were - 0.354 cm (95% LOA, -1.289 to 1.998 cm), 1.354 cm (95% LOA, -0.289 to 2.998 cm), 1.154 cm (95% LOA, -1.002 to 3.311 cm), -0.619 cm (95% LOA, -2.960 to 1.723 cm), respectively. The rate of optimal intubation for new formula 1 (84.69%) was higher than for new formula 2 (55.86%), APLS formula (61.26%), and MFL-based formula. (69.37%). CONCLUSIONS: The prediction accuracy for intubation depth of the new formula 1 was higher than the other formulae. The new formula based on height: D (cm) = 4 + 0.1 × Height (cm) was preferable to APLS formula and MFL-based formula with a high incidence of appropriate endotracheal tube position.

[Clinical features and genetic analysis of a child with acute form of Tyrosinemia type I due to a novel variant of FAH gene].

OBJECTIVE: To analyze the clinical phenotype and genetic basis for a child with acute form of tyrosinemia type I (TYRSN1). METHODS: A child with TYRSN1 who presented at the Gansu Provincial Maternal and Child Health Care Hospital in October 2020 was selected as the subject. The child was subjected to tandem mass spectrometry (MS-MS) and urine gas chromatography-mass spectrometry (GC-MS) for the detection of inherited metabolic disorders, in addition with whole exome sequencing (WES). Candidate variants were validated by Sanger sequencing. RESULTS: The child's clinical features included abdominal distension, hepatomegaly, anemia and tendency of bleeding. By mass spectrometry analysis, her serum and urine tyrosine and succinylacetone levels have both exceeded the normal ranges. WES and Sanger sequencing revealed that she has harbored c.1062+5G>A and c.943T>C (p.Cys315Arg) compound heterozygous variants of the FAH gene, which were inherited from her father and mother, respectively. Among these, the c.943T>C was unreported previously. CONCLUSION: Considering her clinical phenotype and result of genetic testing, the child was diagnosed with TYRSN1 (acute type). The compound heterozygous variants of the FAH gene probably underlay the disease in this child. Above finding has further expanded the spectrum of FAH gene variants, and provided a basis for accurate treatment, genetic counseling and prenatal diagnosis for her family.

Association of Preoperative Vitamin D Deficiency With Retear Rate and Early Pain After Arthroscopic Rotator Cuff Repair: A Retrospective Cohort Study.

Background: Although the function of vitamin D in bone metabolism has been well studied, the question remains whether vitamin D deficiency impairs tendon healing after rotator cuff repair. Purpose: To investigate the correlation between preoperative vitamin D deficiency and the retear rate and pain after arthroscopic rotator cuff repair. Study Design: Cohort study; Level of evidence, 3. Methods: Patients with full-thickness rotator cuff tears who underwent arthroscopic rotator cuff repair between January 2018 and August 2019 were enrolled. Included patients were divided into a control group (vitamin D level ≥20 µg/L) and a deficiency group (vitamin D level <20 µg/L). We investigated the association between preoperative vitamin D level and patient characteristics, MRI findings, pain and function scores (visual analog scale [VAS] for pain; Constant-Murley; University of California, Los Angeles; and American Shoulder and Elbow Surgeons scores), and healing status using the Pearson or Spearman correlation coefficient. The clinical characteristics were compared between the groups using the chi-square test or Fisher exact test. Results: Included were 89 patients (control group, 44 patients; deficiency group, 45 patients). The mean vitamin D levels were 25.07 ± 5.38 and 14.61 ± 3.43 µg/L in the control and deficiency groups, respectively (P < .001); otherwise, there were no significant differences between the groups in the variables under study. Vitamin D levels were not related to age, symptom duration, tear size, extent of retraction, VAS pain score preoperatively and at 6 and 24 months postoperatively, or any function scores. Supraspinatus fatty infiltration and VAS scores at 1 and 3 months postoperatively were significantly associated with vitamin D level (r = -0.360, -0.362, and -0.316, respectively; P < .05 for all). VAS scores were significantly lower in the control group than in the deficiency group at postoperative 1 month (1.09 ± 0.56 vs 1.47 ± 0.66, respectively) and 3 months (1.14 ± 0.77 vs 1.44 ± 0.66) (P < .05 for both). The retear rate was significantly lower in the control group than in the deficiency group (9.09% vs 26.67%, respectively; P < .05). Conclusion: Our study revealed that preoperative vitamin D deficiency was associated with a higher retear rate and early pain (1 and 3 months) after arthroscopic rotator cuff repair.

Effect of head position changes on the depth of tracheal intubation in pediatric patients: A prospective, observational study.

Purpose: The purpose of this study was to investigate the effect of changing head position on the endotracheal tube (ETT) depth and to assess the risk of inadvertent extubation and bronchial intubation in pediatric patients. Methods: Subjects aged 4-12 years old with orotracheal intubation undergoing elective surgeries were enrolled. After induction, the distances between "the ETT tip and the trachea carina" (T-C) were measured using a Disposcope flexible endoscope in head neutral position, 45° extension and flexion, 60° right and left rotation. The distance of the ETT tip movement relative to the neutral position (ΔT-C) was calculated after changing the head positions. The direction of the ETT tip displacement and the adverse events including endobronchial intubation, accidental tracheal extubation, hoarseness and sore throat were recorded. Results: The ETT tip moved toward the carina by 0.5 ± 0.4 cm (P < 0.001) when the head was flexed. After extending the head, the ETT tip moved toward the vocal cord by 0.9 ± 0.4 cm (P < 0.001). Right rotation resulted that the ETT tip moved toward the vocal cord direction by 0.6 ± 0.4 cm (P < 0.001). Moreover, there was no displacement with the head on left rotation (P = 0.126). Subjects with the reinforced ETT had less ETT displacement after changing head position than the taper guard ETT. Conclusion: The changes of head position can influence the depth of the ETT especially in head extension. We recommend using the reinforced ETT to reduce the ETT displacement in pediatrics to avoid intubation complications. Clinical trial registration: [www.ClinicalTrials.gov], identifier, [ChiCTR2100042648].

Seasonal and spatial variability of zooplankton diversity in the Poyang Lake Basin using DNA metabarcoding.

Freshwater ecosystems face multiple threats to their stability globally. Poyang Lake is the largest lake in China, but its habitat has been seriously degraded because of human activities and natural factors (e.g. climate change), resulting in a decline in freshwater biodiversity. Zooplankton are useful indicators of environmental stressors because they are sensitive to external perturbations. DNA metabarcoding is an approach that has gained significant traction by aiding ecosystem conservation and management. Here, the seasonal and spatial variability in the zooplankton diversity were analyzed in the Poyang Lake Basin using DNA metabarcoding. The results showed that the community structure of zooplankton exhibited significant seasonal and spatial variability using DNA metabarcoding, where the community structure was correlated with turbidity, water temperature, pH, total phosphorus, and chlorophyll-a. These results indicated habitat variations affected by human activities and seasonal change could be the main driving factors for the variations of zooplankton community. This study also provides an important reference for the management of aquatic ecosystem health and conservation of aquatic biodiversity.

Serum Cystatin C Level Monitoring for Intervention Opportunity of CBP in Children with Severe Sepsis.

Objective: The aim of this study is to investigate the instruction value of the serum cystatin C (Cys C) level monitoring for intervention opportunity of continuous blood purification technology (CBP) in children with severe sepsis. Methods: 67 children with severe sepsis in the pediatric intensive care unit (PICU) with CBP treatment were retrospectively selected from May 2016 to April 2020. According to the time intervals between the time point of serum Cys C level began to increase (>15 mg/L) and the time point of CBP began, all children were divided into group A (<24 h, 29 cases), group B (24-48 h, 22 cases), and group C (>48 h, 16 cases). The children's general characteristics, vital signs, biochemical parameters, acute physiology and chronic health evaluation (APACHE II), and sequential organ failure assessment (SOFA) scores were evaluated. The influence factors of prognosis of children with severe sepsis were analyzed by multivariate regression analysis. Results: The intervals between the time point of PICU hospitalization and the time point of CBP began and the times of CBP in group A were significantly more than those in group B and C (P < 0.05). There was no statistically significant duration of CBP among three groups (P > 0.05). After follow-up of 28 d, there was no significant difference on the occurrence of coagulation disorders and hypovolemic shock induced by CBP among three groups (P > 0.05). However, the mortality of children in group A was lower than that in group C (P < 0.05). Children in group A had lower APACHE II scores, SOFA scores, serum K+, blood urea nitrogen (BUN), serum creatine (SCr), partial pressure of carbon dioxide (PCO2), and higher partial pressure of oxygen (PO2) than those of children in group C after CBP. (P < 0.05). SOFA scores ≥5 after CBP treatment and the time intervals between the time point of serum Cys C level began to increase (>15 mg/L) and the time point of CBP began ≥24 h were the independent influence factors on the prognosis by multivariate regression analysis. Conclusion: There are significant evidences that continuous blood purification technology within 24 h of serum Cys C level may better control the condition of children with severe sepsis.

Circular RNAs in the pathogenesis of sepsis and their clinical implications: A narrative review.

INTRODUCTION: Sepsis is defined as a life-threatening complication that occurs when the body responds to an infection attacking the host. Sepsis rapidly progresses and patients deteriorate and develop septic shock, with multiple organ failure, if not promptly treated. Currently no effective therapy is available for sepsis; therefore, early diagnosis is crucial to decrease the high mortality rate. Genome-wide expression analyses of patients in critical conditions have confirmed that the expression levels of the majority of genes are changed, suggesting that the molecular basis of sepsis is at the gene level. This review aims to elucidate the role of circular (circ) RNAs in the pathogenesis of sepsis and sepsis-induced organ damage. In addition, the feasibility of using circRNAs as novel diagnostic biomarkers for sepsis is also discussed, as well as circRNA-based therapy. METHOD: This narrative review is based on a literature search using Medline database. Search terms used were "circular RNAs and sepsis", "circRNAs and sepsis", "non-coding RNAs and sepsis", "ncRNAs and sepsis", "circRNAs and septic pathogenesis", "circRNAs and septic model", "circRNAs and septic shock" and "circRNAs, biomarker, and sepsis". RESULTS: Numerous studies indicate that circRNAs might exert pivotal roles in regulating the immune system of the host against various pathogens, such as bacteria and viruses. Dysregulation of circRNA expression levels has been confirmed as an early event in sepsis and associated with the inflammatory response, immunosuppression and coagulation dysfunction. This impairment in regulation eventually leads to multiple organ dysfunctions, including of the kidneys, lungs and heart. CONCLUSION: By investigating the regulation of circRNAs in sepsis, new molecular targets for the diagnosis and intervention of sepsis can be identified. Such an understanding will be important for the development of therapeutic drugs.

Co-targeting WIP1 and PARP induces synthetic lethality in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most fatal cancers. Due to limited strategies for effective treatments, patients with advanced HCC have a very poor prognosis. This study aims to identify new insights in HCC to develop novel strategies for HCC management. METHODS: The role of WIP1 (wild type p53 induced protein phosphatase1) in HCC was analyzed in HCC cells, xenograft model, DEN (Diethylnitrosamine) induced mice liver cancer model with WIP1 knockout mice, and TCGA database. DNA damage was evaluated by Gene Set Enrichment Analysis, western blotting, comet assay, and Immunofluorescence. RESULTS: High expression of WIP1 is associated with the poor prognosis of patients with HCC. Genetically and chemically suppression of WIP1 drastically reduced HCC cell proliferation. Besides, WIP1 knockout retarded DEN induced mice hepato-carcinogenesis. Mechanically, WIP1 inhibition induced DNA damage by increasing H2AX phosphorylation (γH2AX). Therefore, suppression of WIP1 and PARP induced synthetic lethality in HCC in vitro and in vivo by augmenting DNA damage. CONCLUSION: WIP1 plays an oncogenic effect in HCC development, and targeting WIP1-dependent DNA damage repair alone or in combination with PARP inhibition might be a reasonable strategy for HCC management. Video abstract.

[Study on correlation between serum vitamin D level and the curative effect after repair of rotator cuff tears].

OBJECTIVE: To investigate the correlation between serum vitamin D level and clinical outcomes after repair of rotator cuff tears. METHODS: A total 122 patients who met the inclusion criteria and were followed up for 12 months from March 2018 to March 2020 were analyzed retrospectively, including 50 males and 72 females with an average age of(62.10±8.39) years old (ranged, 34 to 82 years old). All patients were divided into deficiency group(vitamin D<20 µg/L) and control group(vitamin D≥20 µg/L), including 62 cases in the deficiency group, with vitamin D (14.80±3.18) µg/L;60 cases in the control group, with vitamin D(25.17±5.64) µg/L. The two groups were compared in terms of age, gender, body mass index(BMI), tear size, degree of retraction, degree of fatty infiltration, injury factors, postoperative pain VAS score, postoperative shoulder joint function score, and re-tear rate. The age of all patients was divided into two categories:<60 years old and ≥60 years old;BMI was divided into <24 kg/m2 and ≥ 24 kg/m2;tear size was divided into ≤3 cm and >3 cm;retraction degree was divided into ≤2 cm and >2 cm;fat infiltration was divided into ≤2 grade and >2 grade;and the course of the disease was ≤3 months and >3 months. The correlation between Sugaya re-tear type and the variables listed above were analyzed and calculated. RESULTS: There were no major complications such as joint infection, anchor withdrawal and revision surgery in any of the 122 patients who were followed up on. There were no statistical differences in age, gender, injury factor, BMI, tear size, degree of retraction, degree of fatty infiltration, and duration of disease between the two groups (P>0.05). The Constant-Murley scores, UCLA scores, and ASES scores of the two groups all improved considerably after surgery(P<0.05);however, there was no statistical differences in the postoperative shoulder function scores between the two groups (P>0.05). There was significant difference in VAS between the two groups 1 month and 3 months after operation, with vitamin D deficiency group scoring higher, and there was no significant differences 6 and 12 months after operation. Tear size(>3 cm), degree of retraction(>2 cm), degree of fatty infiltration(>2 degree) were all shown to be the independent risk factors for retear after surgery by Logistic regression analysis(P<0.05). The comparison between the two groups of patients using a 2×5 row list showed that the Sugaya classification of rotator cuff re-tear(grade Ⅰto Ⅴ) between the vitamin D deficiency group and the control group was statistically different(t=14.228, P=0.007). It was discovered that the Sugaya classification after surgery was statistically different between the two groups. CONCLUSION: Vitamin D deficiency is not correlated with clinical function scores and re-tear rate, however it is associated with the early postoperative pain (1 and 3 months) and the quality of rotator cuff healing (Sugaya classification) after surgery.