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Objective:To characterize the longitudinal and dynamic high-density lipoprotein (HDL) trajectories in critically ill children and explore their correlation with clinical outcomes.Methods:Retrospective cohort study.All critically ill children admitted to the Pediatric Intensive Care Unit (PICU) of West China Hospital, Sichuan University from January 1, 2015 to October 1, 2020 were included in this retrospective study.Group-based trajectory modeling (GBTM) was applied to characterize the HDL trajectories in days 0-6 post-PICU admission and develop HDL trajectory groups.The in-hospital mortality rate was reported as frequency (%) and then compared by the Chi-square test or Fisher′s exact test between HDL trajectory groups.The length of stay (LOS) in the PICU was described by M( Q1, Q3), and its difference between HDL trajectory groups was evaluated by the Kruskal Wallis test.Logistic regression and multiple linear regression were used to determine the correlation between HDL trajectories and clinical outcomes.The primary outcome was in-hospital mortality rate, and the secondary outcome was LOS in the PICU. Results:A total of 4 384 critically ill children were ultimately enrolled in the study, and 6 HDL trajectory groups were developed based on GBTM analyses: group 1 (758 cases), the lowest HDL group; group 2 (1 413 cases), the low HDL group; group 3 (74 cases), the low-to-high HDL group; group 4 (621 cases), the medium HDL group; group 5 (1 371 cases), the high HDL group; and group 6 (147 cases), the highest HDL group.Logistic regression analysis showed that compared with critically ill children in group 1, those belonging to groups 2, 3, 4, 5, and 6 were at lower risks of in-hospital mortality with odds ratio ( OR): 0.475, 95%confidence interval ( CI): 0.352-0.641, P<0.001; OR: 0.093, 95% CI: 0.013-0.679, P=0.019; OR: 0.322, 95% CI: 0.208-0.479, P<0.001; OR: 0.263, 95% CI: 0.185-0.374, P<0.001, and OR: 0.142, 95% CI: 0.044-0.454, P=0.001, respectively.Multiple linear regression analysis revealed that compared with critically ill children in group 1, those belonging to groups 4, 5, and 6 had the trend of shorter LOS in PICU, and the β value and 95% CI were β: -4.332, 95% CI: -5.238- -3.426, P<0.001; β: -3.053, 95% CI: -3.809--2.297, P<0.001; β: -6.281, 95% CI: -7.842--4.721, P<0.001, respectively. Conclusions:The dynamic HDL trajectories during 0-6 days after PICU admission are associated with in-hospital mortality rate of critically ill children.The HDL trajectory at a persistently low level is associated with higher mortality, while the HDL trajectory at a persistently high level or with the trend from a low level rising to a high level shows a lower risk of mortality.It is suggested that the HDL trajectory model may become an indicator to predict the condition and prognosis of critically ill children.

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Objective:To observe any therapeutic effect of combining botulinum toxin type A (BTX-A) with rehabilitation training in treating Parkinson′s disease (PD) patients with striatal foot deformity (SFD).Methods:A total of 68 PD patients with SFD were randomly divided into a control group and a treatment group. Both groups were given routine medication with pramipexole and dopamine receptor agonists and received lower limb rehabilitation training, including passive activity training, strength training and walking training. The treatment group was additionally injected with BTX-A. Sciatic pain was quantified using a visual analogue scale. The Unified Parkinson′s Disease Rating Scale-lower limb motor lower limb motor function (UPDRS-LLM) scale, the Berg balance scale and the modified Barthel index were applied to test all of the participants before the experiment and on the 7th, 14th and 30th day of the treatment.Results:The average scores of the control group on all of measures at were significantly better than those of the control group at the same time points, and by the 14th and 30th day had improved significantly compared with those before treatment.Conclusion:Supplementing rehabilitation training with BTX-A can significantly improve foot deformity and relieve the muscle tension and spastic pain of PD patients with SFD, promoting the motor functioning of their lower limbs, their balance and their performance in the activities of daily living.

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Objective To investigate the diagnostic value of cervical vagus nerve cross-sectional area(CAS)for Parkinson's disease(PD).Methods Thirty patients with PD admitted to the People's Hospital of Zhengzhou University from October 2019 to October 2022 were selected as PD group,25 patients with multiple system atrophy(MSA)admitted to the People's Hospital of Zhengzhou University during the same period were selected as the MSA group,and 30 healthy individuals who underwent physical examination in the People's Hospital of Zhengzhou University during the same period were selected as healthy control group.Cervical vagus CAS of subjects in the three groups were measured by high-resolution ultrasound,and the difference of CAS of cervical vagus nerve was compared among the three groups.The degree of impairment of autonomic nervous function of subjects in the three groups was evaluated by PD autonomic symptom scale(SCOPA-AUT).The diagnostic value of cervical vagus nerve CAS for PD was analyzed by receiver operating characteristic(ROC)curve.Results The CAS of the right cervical vagus nerve of subjects was significantly larger than that of the left in the healthy control group and PD group(P＜0.05);there was no significant difference in CAS of bilateral cervical vagus nerve of subjects in the MSA group(P＞0.05).The CAS and average CAS of bilateral cervical vagus nerve of subjects in the PD group and MSA group were significantly lower than those in the healthy control group(P＜0.01).The CAS of the right vagus nerve of subjects in the MSA group was significantly lower than that in the PD group(P＜0.05);there was no significant difference in CAS and the average CAS of the left vagus nerve between the MSA group and the PD group(P＞0.05).The total score of SCOPA-AUT and gastrointestinal(GI),cardiovascular(CV),urinary(UR)and sexual(SX)scores of subjects in the PD group and MSA group were significantly higher than those in the healthy control group(P＜0.01).The total score of SCOPA-AUT and UR,SX scores of subjects in the MSA group were significantly higher than those in the PD group(P＜0.05).There was no significant difference in temperature(TH)and pupil(PU)of subjects among the three groups(P＞0.05).Pearson correlation analysis showed that the CAS of cervical vagus nerve of PD patients was not correlated with the total score of SCOPA-AUT and the UR,TH,PU,SX scores(r=-0.143,0.281,0.297,0.265,0.312;P＞0.05).The CAS of cervical vagus nerve of PD patients was negatively correlated with GI and CV scores(r=-0.683,-0.373;P＜0.05).ROC curve analysis showed that the area under the curve of cervical vagus nerve for diagnosing PD was 0.870(95％confidence interval:0.773-0.966,P＜0.05);the critical value was 3.064 mm2,the sensitivity was 96％,and the specificity was 67％.The area under the curve of CAS of cervical vagus nerve in differential diagnosis of PD,MSA was 0.680(95％confidence interval:0.537-0.823,P＜0.05).The sensitivity and specificity for the diagnosis of MSA were 68％and 70％when the CAS of the cervical vagus nerve＜2.709 mm2.Conclusion The CAS of cervical vagal nerve has high clinical diagnostic value for PD,and it provides a new way to improve the diagnosis rate of PD.

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Objective:To compare the clinical efficacy of femoral distraction and homeopathic double reverse traction reduction assisted internal fixation in the treatment of Schatzker type IV-VI tibial plateau fractures.Methods:A total of 51 patients (28 males and 23 females) with Schatzker IV-VI tibial plateau fractures treated with femoral distraction or homeopathic double reverse traction reduction from January 2017 to June 2021 in the Second Affiliated Hospital of Wenzhou Medical University were retrospectively analyzed. The average age was 49.6±11.9 years (range, 28-71 years). The time from injury to operation was 4.5±3.0 days (range, 1-15 days). There were 5 cases with combined anterior cruciate ligament injuries and 9 cases with posterior cruciate ligament injuries. Twenty-five cases were treated with femoral distraction reduction (distraction reduction group) and 26 cases with homeopathic double reverse traction reduction (traction reduction group). The operation time, intraoperative blood loss, visual analogue scale (VAS) on the first day after operation, hospitalization time, fracture healing time, and incidence of complications were compared between the two groups. Hospital for Special Surgery (HSS) knee function score at 1, 3, 6, 12 months after operation were also compared.Results:All patients were operated successfully. The operation time was 125.9±35.1 min (range, 60-220 min), and the intraoperative blood loss was 138.4±85.4 ml (range, 30-400 ml). 15 patients received autologous iliac bone grafting and 36 patients received allogeneic bone grafting. The VAS score on the first day after operation was 2.4±0.7 (range, 1-4), the hospital stay was 12.6±3.6 days (range, 7-24 days), and the fracture healing time was 14.6±2.2 weeks (range, 12-21 weeks). All patients were followed up for 16.8±2.8 months (range, 13-25 months). The operation time, intraoperative blood loss and hospital stay in the traction reduction group were 106.2±21.7 min, 86.9±42.6 ml and 11.6±3.3 days, respectively, which were less than 146.4±34.9 min, 192.0±86.2 ml and 13.7±3.6 days in the distraction reduction group. The differences were statistically significant ( P<0.05). The HSS scores of traction reduction group at 1 month and 3 months after operation were 83.8±1.7 and 86.7±2.0, which were higher than those of distraction reduction group (81.0±2.6 and 84.9±2.6), and the differences were statistically significant ( P<0.05). There was no significant difference in HSS score between the two groups at 6 and 12 months after operation ( P>0.05). Conclusion:The internal fixation treatment of Schatzker type IV-VI tibial plateau fracture assisted with homeopathic double reverse traction reduction can reduce the amount of intraoperative blood loss, operation time and hospital stay, and improve the knee function in the early postoperative period.

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Long non-coding RNAs (lncRNAs) can affect various biological processes, such as cell proliferation, migration, and angiogenesis, by regulating chromosome remodeling, gene transcription or protein translation. This review summarizes recent research progress in the role of lncRNAs in the occurrence and development of infantile hemangioma, in order to provide new directions for the treatment of infantile hemangioma.

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Objective:To investigate the role of plasma neurofilament light chain (NfL) in diagnosing and differentiating Parkinson's disease (PD) and multiple system atrophy-Parkinsonian subtype (MSA-P).Methods:Forty PD patients and 23 MSA-P patients admitted to Department of Neurology, Henan Provincial People's Hospital from June 2019 to December 2021 were recruited; 27 healthy subjects accepted physical examination during the same period were selected as controls. Ultrasensitive Simoa technology was used to measure the plasma NfL. Differences in clinical data and plasma NfL were compared among all subjects. Correlations of plasma NfL with clinical characteristics, such as disease course, Hoehn-Year (H-Y) staging, Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA), Scale for Outcomes in Parkinson's Disease for Autonomic Symptoms (SCOPA-AUT) and levodopa equivalent daily dosage (LEDD), were analyzed with Pearson correlations. Receiver operating characteristic (ROC) curve was used to analyze the value of plasma NfL in diagnosing and differentiating PD and MSA-P.Results:Compared with MSA-P group, PD group had significantly longer disease course and statistically lower scores of UPDRS-II and SCOPA-AUT ( P<0.05). The plasma NfL in MSA-P group, PD group and healthy control group was decreased successively ([37.69±10.47] pg/mL, [17.85±4.23] pg/mL, [12.86±3.14] pg/mL, respectively), with statistical differences ( P<0.05). In MSA-P patients, Pearson correlations showed positive correlation between plasma NfL and age ( r=0.442, P=0.035); and Partial correlations showed positive correlations between plasma NfL and scores of UPDRS-I and UPDRS-III ( P<0.05), and plasma NfL showed no significant correlation with H-Y staging, UPDRS-III, MoCA, LEDD or SCOPA-AUT scores ( P>0.05). In PD patients, Pearson correlations showed that plasma NfL was positively correlated with age ( r=0.342, P=0.031); partial correlations showed that plasma NfL was positively correlated with H-Y staging and UPDRS-III, and negatively correlated with MoCA scores ( P<0.05); plasma NfL showed no significant correlation with disease course, scores of UPDRS-I and UPDRS-II, LEDD, and SCOPA-AUT scores ( P>0.05). ROC curve showed that the area under the curve (AUC) of plasma NfL in diagnosing PD was 0.814 (95% CI: 0.712-0.920, P<0.001); AUC of plasma NfL in differentiating and diagnosing PD and MSA-P was 0.980 (95% CI: 0.954-1.000, P<0.001); AUC of plasma NfL in diagnosing MSA-P was 0.998 (95% CI: 0.993-1.000, P<0.001). Conclusions:Plasma NfL is correlated with severity of motor symptoms in MSA-P patients; plasma NfL is correlated with cognitive function and disease course in PD patients. Besides, plasma NfL has high sensitivity and specificity in differentiating PD and MSA-P, therefore, plasma NfL could serve as a biomarker to diagnosis and differentiate PD.

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The occurrence of cancer entails a series of genetic mutations that favor uncontrollable tumor growth. It is believed that various factors collectively contribute to cancer, and there is no one single explanation for tumorigenesis. Epigenetic changes such as the dysregulation of enzymes modifying DNA or histones are actively involved in oncogenesis and inflammatory response. The methylation of lysine residues on histone proteins represents a class of post-translational modifications. The human Jumonji C domain-containing (JMJD) protein family consists of more than 30 members. The JMJD proteins have long been identified with histone lysine demethylases (KDM) and histone arginine demethylases activities and thus could function as epigenetic modulators in physiological processes and diseases. Importantly, growing evidence has demonstrated the aberrant expression of JMJD proteins in cancer and inflammatory diseases, which might serve as an underlying mechanism for the initiation and progression of such diseases. Here, we discuss the role of key JMJD proteins in cancer and inflammation, including the intensively studied histone lysine demethylases, as well as the understudied group of JMJD members. In particular, we focused on epigenetic changes induced by each JMJD member and summarized recent research progress evaluating their therapeutic potential for the treatment of cancer and inflammatory diseases.

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The binding of SARS-CoV-2 nucleocapsid (N) protein to both the 5'- and 3'-ends of genomic RNA has different implications arising from its binding to the central region during virion assembly. However, the mechanism underlying selective binding remains unknown. Herein, we performed the high-throughput RNA-SELEX (HTR-SELEX) to determine the RNA-binding specificity of the N proteins of various SARS-CoV-2 variants as well as other {beta}-coronaviruses and showed that N proteins could bind two unrelated sequences, both of which were highly conserved across all variants and species. Interestingly, both these sequence motifs are virtually absent from the human transcriptome; however, they exhibit a highly enriched, mutually complementary distribution in the coronavirus genome, highlighting their varied functions in genome packaging. Our results provide mechanistic insights into viral genome packaging, thereby increasing the feasibility of developing drugs with broad-spectrum anti-coronavirus activity by targeting RNA binding by N proteins.

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Replicons are synthetic viral RNA molecules that recapitulate the self-replicating activities of the virus but are missing its infectivity potential. Here, we report on a scalable pipeline to generate a replicon of any SARS-CoV-2 strain using de-novo synthesis. Our pipeline relies only on publicly available sequencing data without requiring access to any material, simplifying logistical and bureaucratic issues of sample acquisition. In addition, our system retains the nucleotide sequence of most of the SARS-CoV-2 full genome and therefore better captures its underlying genomic and biological functions as compared to the popular pseudotypes or any replicon system published to-date. We utilized our system to synthesize a SARS-CoV-2 non-infectious version of the Beta strain. We then confirmed that the resulting RNA molecules are non-infectious and safe to handle in a BSL2/CL2 facility. Finally, we show that our replicon can be specifically inhibited by molnupiravir and RNAi treatments, demonstrating its utility for drug research and development.

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Objective:To compare the effects of milnacipran and paroxetine on anxiety state and headache severity of patients with generalized anxiety disorder (GAD).Methods:Ninety-six patients with GAD treated in Zaozhuang Mental Health Center from January 2019 to September 2020 were selected and randomly divided into the paroxetine group (treatment with oral paroxetine) and the milnacipran group (treatment with oral milnacipran), each group with 48 cases. A course of treatment consists of 4 weeks. After 3 months of regular medication, the clinical efficacy, Hamilton Anxiety Scale (HAMA) scores, visual analogue scale (VAS) scores, migraine-specific quality of life questionnaire (MSQ V2.1) scores, and Headache Impact Test-6 (HIT-6) scores were compared between the two groups. Adverse reactions during the treatment were recorded in both groups.Results:The total effective rate in the milnacipran group at 4 weeks and 3 months after treatment were significantly higher than those in the paroxetine group: 47.92%(23/48) vs. 22.92%(11/48), χ2 = 6.56, P<0.05; 75.00%(36/48) vs. 51.47%(26/48), χ2 = 4.55, P<0.05. After treatment for 4 weeks and 3 months, the HAMA scores, VAS scores, MSQ V2.1 scores and HIT-6 scores in the milnacipran group were significantly lower than those in the paroxetine group ( P<0.05). The difference of incidence of adverse reactions in the two groups had no statistical significance ( P>0.05). Conclusions:For patients with GAD, the treatment effect of milnacipran is more significant than paroxetine, which can not only reduce patients′ anxiety state and headache degree, but also improve their specific quality of life, with high safety.

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Objective:To analyze demographic and clinical characteristics of infantile hemangioma (IH) , and to explore related risk factors for IH.Methods:A multicenter case-control study was conducted. IH patients (case group) and healthy children (control group) were collected from West China Hospital of Sichuan University, West China Second University Hospital of Sichuan University and Yulin Community Central Hospital of Chengdu from October 2018 to December 2020. The data on patients′ demographic characteristics, and risk factors during their mothers′ pre-pregnancy, pregnancy and perinatal period were collected and retrospectively analyzed. Univariate and multivariate analyses were performed using binary logistic regression.Results:A total of 1 479 patients with IH and 1 086 healthy children were included in this study. There were 456 males and 1 023 females in the case group, with the age being 3.74 ± 2.82 months, and there were 359 males and 727 females in the control group, with the age being 3.95 ± 2.77 months. There was no significant difference in the gender ratio, age, ethnic composition, birth weight or birth height between the case group and control group (all P > 0.05) . IH lesions mostly affected the head and face (564 cases, 38.1%) , followed by the trunk (449 cases, 30.6%) and limbs (356 cases, 24.1%) . At the visit, 1 109 (75.0%) patients presented with proliferating IH, 1 059 (71.6%) with superficial IH, and 1 306 (88.3%) with focal IH. The IH lesion area ranged from 0.01 to 168.00 (6.24 ± 12.91) cm 2, and the segmental IH area ranged from 7.50 to 168.00 (32.17 ± 26.94) cm 2. Univariate logistic regression analysis showed some factors influencing the occurrence of IH (all P < 0.05) , including pre-pregnancy factors (delivery history and miscarriage history) , pregnancy factors (fetal distress, cord entanglement, history of threatened abortion, placenta previa, oligohydramnios, gestational hypothyroidism, gestational anemia, history of progesterone supplementation, history of thyroxine drug use, history of uterus myomas) , and perinatal factors (including fetal position, gestational weeks, premature rupture of membranes and preterm premature rupture of membranes) . Multivariate binary logistic regression adjusted analysis showed that fetal breech presentation, preterm birth, cord entanglement and history of thyroxine drug use during pregnancy did not influence the occurrence of IH (all P > 0.05) ; the delivery history was the strongest independent risk factor for IH (adjusted OR = 5.624, 95% CI: 4.275 to 7.398, P < 0.001) , and gestational hypothyroidism and history of uterus myomas were protective factors for IH. Conclusions:In this study, the average age of IH patients at visit was 4 months, skin lesions mostly occurred on the head and face, and most were superficial and focal in the proliferative stage. The occurrence and development of IH may be associated with placental diseases, hypoxia, maternal hormone levels during pregnancy, etc.

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Objective:To investigate the effect of the glucose transporter 1 (Glut-1) inhibitor resveratrol on the activity of infantile hemangioma (IH) -derived endothelial cells (HemEC) .Methods:IH tissues were collected from 4 cases of proliferating IH and 4 cases of involuting IH, and immunohistochemical study was performed to determine the Glut-1 expression. Primary HemEC were extracted from 4 proliferating IH tissues, real-time fluorescence-based quantitative PCR (qPCR) and Western blot analysis were performed to determine the mRNA and protein expression of Glut-1 in HemEC and human umbilical vein endothelial cells (HUVEC) , respectively. HemEC were cultured in vitro and treated with 0 (control group) , 50, 100, 200, 400 and 800 μmol/L resveratrol for 24 hours, respectively. Cell counting kit-8 (CCK8) assay was performed to evaluate the proliferative ability of HemEC in the above groups, and the 50% inhibitory concentration (IC50) was calculated. The migratory ability and apoptosis level of HemEC were assessed by Transwell assay and flow cytometry, respectively. Intergroup comparisons were performed using t test or analysis of variance, and multiple comparisons were performed using least significant difference- t test. Results:Immunohistochemical study showed that Glut-1 was expressed in vascular endothelial cells derived from both proliferating and involuting IH tissues, and the Glut-1 expression was abundant in the proliferating IH but markedly decreased in the involuting IH tissues. The mRNA and protein expression levels of Glut-1 were significantly higher in HemEC (1.793 ± 0.041, 1.959 ± 0.144, respectively) than in HUVEC (0.820 ± 0.073, 0.648 ± 0.046, t = 16.35, 12.28, respectively, both P < 0.001) . After the treatment with Glut-1 inhibitor resveratrol at different concentrations, the proliferative ability of HemEC significantly differed among the control group, 50-, 100-, 200-, 400- and 800-μmol/L resveratrol groups ( F = 1 043.00, P < 0.001) , and was significantly lower in all the resveratrol groups than in the control group (all P < 0.05) . The IC50 of resveratrol was calculated to be 150 μmol/L by using GraphPad Prism 8 software. Transwell assay and flow cytometry showed significantly decreased number of migratory HemEC but significantly increased apoptosis rate respectively in the 150 μmol/L resveratrol group (61 ± 5, 13.01% ± 0.45%, respectively) compared with the control group (150 ± 6, 3.93% ± 0.68%, t = 15.11, 19.34, respectively, both P < 0.001) . Conclusion:The key glycolytic enzyme Glut-1 was highly expressed in proliferating IH tissues and HemEC, and resveratrol could inhibit the proliferation and migration of HemEC, but promote their apoptosis.

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Rejection after lung transplantation, including acute rejection (AR) and chronic rejection manifested with chronic lung allograft dysfunction (CLAD), is the main factor affecting the long-term survival of allografts. Exosome, a type of extracellular nanovesicle for intercellular communication among eukaryotic cells, could carry complex biological information and participate in various physiological and pathological processes. Exosome has become a critical immune medium in rejection, regulates the incidence and development of rejection through multiple pathways, and also plays a key role in the monitoring and management of rejection. In this article, the type of rejection after lung transplantation, the mechanism underlying the role of exosome in regulating rejection, exosome acting as biomarkers and the application in rejection treatment were reviewed, aiming to provide a novel direction for comprehensive diagnosis and treatment of rejection following lung transplantation.

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Litter decomposition is critical to stream biogeochemical cycles. Metal pollution from past or present mining activities seriously threatens stream ecosystems. However, its effects on litter decomposition in streams remain unclear. A field litterbag experiment was conducted to determine the direct (i.e., via changes in stream water quality: a mine-affected vs. forest stream) and indirect (i.e., via changes in litter traits: polluted vs. non-polluted litter) effects of metal pollution from mining activities on leaf litter decomposition (total vs. microbial-driven) and the associated microbial activity and community composition in streams. Platanus acerifolia leaf litter collected from a polluted and a non-polluted site was enclosed in fine and coarse mesh bags and incubated in a mine-affected stream and a forest stream. The litter from the polluted site had a higher Pb, Zn, Cd, N, soluble sugar concentrations, specific leaf area and pH, and lower leaf toughness and lignin concentration than the litter from the non-polluted site. After incubation in situ, litter mass loss did not significantly differ between streams, but the mine-affected stream had a greater impact on total-driven decomposition rates than microbial-driven decomposition rates. Polluted litter had a significantly higher decomposition rate than non-polluted litter. The decomposition potential of polluted litter produces faster nutrient cycling and supports higher microbial colonization. Litter traits and decomposer community type modulate the influence of metal pollution on litter decomposition. The results suggest that the indirect effects of mining activities on litter decomposition were stronger than the direct effects.

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The emergence of novel SARS-CoV-2 genetic variants that may alter viral fitness highlights the urgency of widespread next-generation sequencing (NGS) surveillance. To profile genetic variants, we developed and clinically validated a hybridization capture SARS-CoV-2 NGS assay, integrating novel methods for panel design using dsDNA biotin-labeled probes, and built accompanying software. The positive and negative percent agreement were defined in comparison to an orthogonal RT-PCR assay (PPA and NPA: both 96.7%). The limit of detection was established to be 800 copies/ml with an average fold-enrichment of 46,791x. We identified novel 107 mutations, including 24 in the functionally-important spike protein. Further, we profiled the full nasopharyngeal microbiome using metagenomics and found overrepresentation of 7 taxa and macrolide resistance in SARS-CoV-2-positive patients. This hybrid capture NGS assay, coupled with optimized software, is a powerful approach to detect and comprehensively map SARS-CoV-2 genetic variants for tracking viral evolution and guiding vaccine updates. TEASERThis is the first target hybridization capture-based NGS assay to detect SARS-CoV-2 genetic variants for tracking viral evolution.

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Objective:To investigate the correlation between total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio and unstable carotid plaque.Methods:From February 2021 to May 2021, adult patients with asymptomatic carotid atherosclerotic plaque admitted to the Department of Neurology, the First People's Hospital of Lianyungang were retrospectively enrolled. The demographic and related clinical data were collected. Carotid artery plaques were detected by ultrasound, and the subjects were divided into a stable plaque group and an unstable plaque group. Multivariate logistic regression analysis was used to assess the independent risk factors for unstable carotid plaques. Receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of TC/HDL-C ratio for unstable carotid plaques. Results:A total of 362 patients with asymptomatic carotid atherosclerotic plaque were enrolled, including 226 (62.43%) in the stable plaque group and 136 (37.57%) in the unstable plaque group. Multivariate logistic regression analysis showed that after adjusting for confounding factors, only TC/HDL-C ratio was the independent risk factor for unstable carotid plaque (taking the 1 st quintile array of TC/HDL-C ratio as a reference, the 4 th quintile array: odds ratio 3.13, 95% confidence interval 1.50-6.55, P=0.002; the 5 th quintile array: odds ratio 6.75, 95% confidence interval 3.21-14.22, P<0.001). ROC curve analysis showed that the area under the curve of TC/HDL-C ratio for predicting unstable carotid plaque was 0.691 (95% confidence interval 0.634-0.748; P<0.001), the optimal cut-off value was 4.38, and the sensitivity and specificity were 50.0% and 82.7%, respectively. Conclusion:TC/HDL-C ratio is an independent risk factor for unstable carotid plaques and has a certain predictive value for unstable carotid plaques.

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A significant proportion of non-small cell lung cancer (NSCLC) patients experience accumulating chemotherapy-related adverse events, motivating the design of chemosensitizating strategies. The main cytotoxic damage induced by chemotherapeutic agents is DNA double-strand breaks (DSB). It is thus conceivable that DNA-dependent protein kinase (DNA-PK) inhibitors which attenuate DNA repair would enhance the anti-tumor effect of chemotherapy. The present study aims to systematically evaluate the efficacy and safety of a novel DNA-PK inhibitor M3814 in synergy with chemotherapies on NSCLC. We identified increased expression of DNA-PK in human NSCLC tissues which was associated with poor prognosis. M3814 potentiated the anti-tumor effect of paclitaxel and etoposide in A549, H460 and H1703 NSCLC cell lines. In the four combinations based on two NSCLC xenograft models and two chemotherapy, we also observed tumor regression at tolerated doses

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Lung cancer, which is exacerbated by environmental pollution and tobacco use, has become the most common cause of cancer-related deaths worldwide, with a five-year overall survival rate of only 19% (Siegel et al., 2020; Yang et al., 2020; Yu and Li, 2020). Nearly 85% of lung cancers are non-small cell lung cancers, of which lung adenocarcinoma is the most common subtype accounting for 50% of non-small cell lung cancer cases. At present, radiotherapy is the primary therapeutic modality for lung cancer at different stages, with significant prolongation of survival time (Hirsch et al., 2017; Bai et al., 2019; Shi et al., 2020). Irradiation can generate reactive oxygen species (ROS) through the radiolysis reaction of water and oxygen, cause DNA damage and oxidative stress, and subsequently result in cancer cell death (Kim et al., 2019). Nevertheless, radioresistance seriously hinders the success of treatment for lung cancer, owing to local recurrence and distant metastasis (Huang et al., 2021). Compared with small cell lung cancer, non-small cell lung cancer shows more tolerance to radiotherapy. Therefore, it is of great importance to decipher key mechanisms of radioresistance and identify effective molecular radiosensitizers to improve patient survival.

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Rhythm of blood pressure refers to the circadian variation of blood pressure, which is regulated by clock genes. However, the rhythm disorder of blood pressure increases the risk of stroke. Taking the process of blood pressure regulation as a clue and focusing on the clock gene pathway, this article explores the possible mechanism of period gene regulating renin-angiotensin-aldosterone system in rhythm of blood pressure, so as to provide reference for the in-depth study of the relevant mechanism of rhythm disorder of blood pressure and search for a new target for the primary prevention of cerebrovascular diseases.

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The oxidative coupling of imines to ketazine with molecular oxygen is a green process towards the synthesis of hydrazine or hydrazine hydrate, which could efficiently address the economic and environmental issues of the traditional Raschig or peroxide-ketazine process. Herein, we developed an efficient heterogeneous base-free benzophenone imine oxidative coupling route with O2 catalyzed by Cu/CuO x /carbon materials derived from MOFs under mild conditions. Under optimized conditions, the conversion of BI is up to 98.2% and the selectivity of ketamine is 94.9%. This catalyst has excellent structure stability, recycling, and regeneration performance, owing to the carbonization of organic ligands of MOF at high temperature. More importantly, it is confirmed that the metallic Cu core is essential to improve the catalytic performance of the CuO shell in the BI oxidative coupling reaction, due to the promotion of electron transfer in the CuO surface, making dissolved O2 molecules more easily insert oxygen vacancies. This strategy might open an avenue to the sustainable catalytic synthesis of hydrazine or hydrazine hydrate.