Long non-coding RNA SNHG17 may function as a competitive endogenous RNA in diffuse large B-cell lymphoma progression by sponging miR-34a-5p.

We investigated the functional mechanism of long non-coding small nucleolar host gene 17 (SNHG17) in diffuse large B-cell lymphoma (DLBCL). lncRNAs related to the prognosis of patients with DLBCL were screened to analyze long non-coding small nucleolar host gene 17 (SNHG17) expression in DLBCL and normal tissues, and a nomogram established for predicting DLBCL prognosis. SNHG17 expression in B-cell lymphoma cells was detected using qPCR. The effects of SNHG17 with/without doxorubicin on the proliferation and apoptosis of DoHH2 and Daudi were detected. The effects of combined SNHG17 and doxorubicin were analyzed. The regulatory function of SNHG17 in DLBCL was investigated using a mouse tumor xenotransplantation model. RNA sequencing was used to analyze the signaling pathways involved in SNHG17 knockdown in B-cell lymphoma cell lines. The target relationships among SNHG17, microRNA, and downstream mRNA biomolecules were detected. A higher SNHG17 level predicted a lower survival rate. SNHG17 was highly expressed in DLBCL patient tissues and cell lines. We established a prognostic model containing SNHG17 expression, which could effectively predict the overall survival rate of DLBCL patients. SNHG17 knockdown inhibited the proliferation and induced the apoptosis of B-cell lymphoma cells, and the combination of SNHG17 and doxorubicin had a synergistic effect. SNHG17, miR-34a-5p, and ZESTE gene enhancer homolog 2 (EZH2) had common hypothetical binding sites, and the luciferase reporter assay verified that miR-34a-5p was the direct target of SNHG17, and EZH2 was the direct target of miR-34a-5p. The carcinogenic function of SNHG17 in the proliferation and apoptosis of DLBCL cells was partially reversed by a miR-34a-5p inhibitor. SNHG17 increases EZH2 levels by inhibiting miR-34a-5p. Our findings indicate SNHG17 as critical for promoting DLBCL progression by regulating the EZH2 signaling pathway and sponging miR-34a-5p. These findings provide a new prognostic marker and therapeutic target for the prognosis and treatment of DLBCL.

[Impact of the environmental layout of the neonatal intensive care unit on clinical outcomes and neurological development in very/extremely preterm infants]. / 新生儿重症监护室环境布局对极/è¶ æ—©äº§å„¿ä¸´åºŠç»“å±€åŠç¥žç»å‘è‚²çš„å½±å“.

OBJECTIVES: To investigate the impact of the environmental layout of the neonatal intensive care unit (NICU) on clinical outcomes and neurological development in very/extremely preterm infants. METHODS: A total of 304 very/extremely preterm infants admitted to Children's Hospital of Chongqing Medical University between January 2021 and June 2022 within 24 hours after birth were included in this retrospective cohort study. Based on different environmental layouts in the NICU, the infants were divided into two groups: centralized layout group (n=157) and decentralized layout group (n=147). The clinical outcomes and Test of Infant Motor Performance (TIMP) scores at corrected gestational age between 34 to 51+6 weeks were compared between the two groups. RESULTS: The decentralized layout group had lower incidence rates of bronchopulmonary dysplasia (44.9% vs 62.4%, P<0.05) and intracranial hemorrhage (17.7% vs 28.0%, P<0.05) than the centralized layout group. The cure rate was higher in the decentralized layout group compared to the centralized layout group (68.7% vs 56.7%, P<0.05). The decentralized layout group had higher TIMP scores than the centralized layout group at corrected gestational age between 34 to 51+6 weeks (P<0.05). CONCLUSIONS: The decentralized layout of the NICU exhibits positive effects on the clinical outcomes and early neurological development compared to the centralized layout in very/extremely preterm infants.

Pan-glioma analyses reveal species- and tumor-specific regulation of neuron-glioma synapse genes by lncRNAs.

Gliomas are highly heterogeneous and aggressive. Malignant cells in gliomas can contact normal neurons through a synapse-like structure (called neuron-to-glioma synapse, NGS) to promote their proliferation, but it is unclear whether NGS gene expression and regulation show species- and tumor-specificity. This question is important in that many anti-cancer drugs are developed upon mouse models. To address this question, we conducted a pan-glioma analysis using nine scRNA-seq datasets from humans and mice. We also experimentally validated the key element of our methods and verified a key result using TCGA datasets of the same glioma types. Our analyses revealed that NGS gene expression and regulation by lncRNAs are highly species- and tumor-specific. Importantly, simian-specific lncRNAs are more involved in NGS gene regulation than lncRNAs conserved in mammals, and transgenic mouse gliomas have little in common with PDX mouse models and human gliomas in terms of NGS gene regulation. The analyses suggest that simian-specific lncRNAs are a new and rich class of potential targets for tumor-specific glioma treatment, and provide pertinent data for further experimentally and clinically exmining the targets.

Randomness accelerates the dynamic clearing process of the COVID-19 outbreaks in China.

During the implementation of strong non-pharmaceutical interventions (NPIs), more than one hundred COVID-19 outbreaks induced by different strains in China were dynamically cleared in about 40 days, which presented the characteristics of small scale clustered outbreaks with low peak levels. To address how did randomness affect the dynamic clearing process, we derived an iterative stochastic difference equation for the number of newly reported cases based on the classical stochastic SIR model and calculate the stochastic control reproduction number (SCRN). Further, by employing the Bayesian technique, the change points of SCRNs have been estimated, which is an important prerequisite for determining the lengths of the exponential growth and decline phases. To reveal the influence of randomness on the dynamic zeroing process, we calculated the explicit expression of the mean first passage time (MFPT) during the decreasing phase using the relevant theory of first passage time (FPT), and the main results indicate that random noise can accelerate the dynamic zeroing process. This demonstrates that powerful NPI measures can rapidly reduce the number of infected people during the exponential decline phase, and enhanced randomness is conducive to dynamic zeroing, i.e. the greater the random noise, the shorter the average clearing time is. To confirm this, we chose 26 COVID-19 outbreaks in various provinces in China and fitted the data by estimating the parameters and change points. We then calculated the MFPTs, which were consistent with the actual duration of dynamic zeroing interventions.

Threshold conditions for curbing COVID-19 with a dynamic zero-case policy derived from 101 outbreaks in China.

By 31 May 2022, original/Alpha, Delta and Omicron strains induced 101 outbreaks of COVID-19 in mainland China. Most outbreaks were cleared by combining non-pharmaceutical interventions (NPIs) with vaccines, but continuous virus variations challenged the dynamic zero-case policy (DZCP), posing questions of what are the prerequisites and threshold levels for success? And what are the independent effects of vaccination in each outbreak? Using a modified classic infectious disease dynamic model and an iterative relationship for new infections per day, the effectiveness of vaccines and NPIs was deduced, from which the independent effectiveness of vaccines was derived. There was a negative correlation between vaccination coverage rates and virus transmission. For the Delta strain, a 61.8% increase in the vaccination rate (VR) reduced the control reproduction number (CRN) by about 27%. For the Omicron strain, a 20.43% increase in VR, including booster shots, reduced the CRN by 42.16%. The implementation speed of NPIs against the original/Alpha strain was faster than the virus's transmission speed, and vaccines significantly accelerated the DZCP against the Delta strain. The CRN ([Formula: see text]) during the exponential growth phase and the peak time and intensity of NPIs were key factors affecting a comprehensive theoretical threshold condition for DZCP success, illustrated by contour diagrams for the CRN under different conditions. The DZCP maintained the [Formula: see text] of 101 outbreaks below the safe threshold level, but the strength of NPIs was close to saturation especially for Omicron, and there was little room for improvement. Only by curbing the rise in the early stage and shortening the exponential growth period could clearing be achieved quickly. Strengthening China's vaccine immune barrier can improve China's ability to prevent and control epidemics and provide greater scope for the selection and adjustment of NPIs. Otherwise, there will be rapid rises in infection rates and an extremely high peak and huge pressure on the healthcare system, and a potential increase in excess mortality.

Uncovering the extensive trade-off between adaptive evolution and disease susceptibility.

Favored mutations in the human genome may make the carriers adapt to changing environments and lifestyles but also susceptible to specific diseases. The scale and details of the trade-off between adaptive evolution and disease susceptibility are unclear because most favored mutations in different populations remain unidentified. As no statistical test can discriminate favored mutations from nearby hitchhiking neutral ones, we report a deep-learning network (DeepFavored) to integrate multiple statistical tests and divide identifying favored mutations into two subtasks. We identify favored mutations in three human populations and analyzed the correlation between favored/hitchhiking mutations and genome-wide association study (GWAS) sites. Both favored and hitchhiking neutral mutations are enriched in GWAS sites with population-specific features, and the enrichment and population specificity are prominent in genes in specific Gene Ontology (GO) terms. These provide evidence for extensive and population-specific trade-offs between adaptive evolution and disease susceptibility. The unveiled scale helps understand and investigate differences and diseases of humans.

miR-22-3p as a potential biomarker for coronary artery disease based on integrated bioinformatics analysis.

Background: Coronary artery disease (CAD) is a common cardiovascular disease that has attracted attention worldwide due to its high morbidity and mortality. Recent studies have shown that abnormal microRNA (miRNA) expression is effective in CAD diagnoses and processes. However, the potential relationship between miRNAs and CAD remains unclear. Methods: Microarray datasets GSE105449 and GSE28858 were downloaded directly from the Gene Expression Omnibus (GEO) to identify miRNAs involved in CAD. Target gene prediction and enrichment analyses were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results: There were nine differentially expressed miRNAs in CAD patients compared to the controls. A total of 352 genes were predicted and subjected to GO analysis, which showed that differentially expressed genes (DEGs) were mainly associated with axon guidance, neuron projection guidance, neuron-to-neuron synapses, and postsynaptic density. According to the KEGG pathway analysis, the most enriched pathways were those involved in transcriptional misregulation in cancer, growth hormone synthesis, secretion and action, endocrine resistance, axon guidance, and Cushing syndrome. Pathway analysis was mainly involved in the HIPPO and prion disease signaling pathways. Furthermore, a competing endogenous RNA (ceRNA) interaction network centered on miR-22-3p revealed eight related transcription factors in the cardiovascular system. The receiver operating characteristic (ROC) curve analysis suggested that miR-22-3p may be a better CAD predictor. Conclusion: The results indicate that miR-22-3p may function in pathophysiological CAD processes. Our study potentiates miR-22-3p as a specific biomarker for diagnosing CAD.

[Analysis of Clinical Characteristics and Prognostic Factors of Patients with Limited-Stage Mantle Cell Lymphoma].

OBJECTIVE: To investigate the clinical characteristics, prognostic factors, and treatment outcomes of patients with limited-stage (Ann Arbor stage I or II) mantle cell lymphoma (MCL). METHODS: Examining consecutive the clinical characteristics, treatment outcomes and prognostic factors of 47 patients with stage I or II MCL diagnosed in Affiliated Tumor Hospital of Guangxi Medical University from January 2005 to June 2020 were analyzed retrospectively. RESULTS: The median age of patients was 62(37-78) years old. 36 patients were male, accounting for 76.6% of the whole. Among these, 74.5% (n=35) of the diagnoses were estimated at II stage. According to Mantle cell lymphoma International Prognostic Index (MIPI), 28 patients (59.6%) were classified as low risk. Patients who received first-line treatment and could be evaluated received rituximab combined chemotherapy, chemotherapy alone, cytarabine containing chemotherapy or chemotherapy combined with local radiotherapy, the different first-line therapies did not affect the complete response (CR) rate of patients (P＞0.05). The median follow-up time was 81.5 months, the 5-year progression-free survival (PFS) was 37.4% and the 5-year overall survival (OS) rate was 80.6%. Multivariate analysis showed that Ki-67＞30% (P＜0.05) the independent adverse prognostic factor for PFS and OS. CONCLUSION: Limited-stage MCL is rare. Patients with limited-stage MCL had a better outcome than those with III-IV stage MCL. Patients with limited-stage MCL whose Ki-67≤30% had better PFS and OS.

A Study of Familial Amyloid Polyneuropathy Induced by the TTR Val30Leu Mutation in China.

INTRODUCTION: Familial amyloid polyneuropathy is currently prevalent worldwide as the transthyretin (TTR) Val30Met mutation, and there are other types of mutations. The purpose of this study was to understand the clinical manifestations, electrophysiological characteristics, and outcomes of hormone-related therapy in patients with the TTR Val30Leu mutation in China. METHODS: Clinical data were collected from 9 members of a family with the TTR Val30Leu mutation in China, and blood samples of 7 members of the family were sequenced. The electrophysiological examinations of 4 of them were collected and analysed. RESULTS: A total of 7 people had the TTR gene c.148G>T missense mutation and the TTR protein Val30Leu mutation in this family, and the positive members all had similar symptoms, such as limb paraesthesia and gastrointestinal symptoms. In addition, electrophysiological examination showed abnormal nerve conduction velocity in all 4 patients. CONCLUSIONS: The clinical manifestations of this mutation involve mainly limb sensory or motor disorders or gastrointestinal symptoms or both, and the electrophysiological examination shows neurogenic damage.

Pharmacokinetic/pharmacodynamic-guided gentamicin dosing in critically ill patients: a revisit of the Hartford nomogram.

The appropriateness of the Hartford nomogram based on 7 mg/kg gentamicin with administration interval adjustment is questioned in critically ill patients. This study aimed to perform a pharmacokinetic/pharmacodynamic (PK/PD) evaluation of the Hartford nomogram and to assess the influence of PK/PD indices on gentamicin dosing. Gentamicin data were extracted from a critical care database to construct the population PK model. Simulations were performed to evaluate the probability of target attainment (PTA) and risk of toxicity for the gentamicin Hartford nomogram. Cmax/MIC ≥ 10 and AUC/MIC ≥ 100 were the PK/PD targets considered, and the non-toxicity targets included concentration < 0.5 mg/L for at least 4 h within a dosing interval and trough concentration < 1 mg/L. A one-compartment model was optimal to describe gentamicin PKs, and creatinine clearance (CLCr) was included as a time-varying covariate on gentamicin clearance. The PTA of Cmax/MIC ≥ 10 (MIC = 1 mg/L) for the Hartford nomogram was suboptimal after the first dose but was desirable (near or greater than 90%) at steady-state, and > 90% PTA based on AUC/MIC ≥ 100 was readily achieved after the first dose in patients with CLCr < 60 mL/min. Significant PTA differences between the PK/PD targets were observed at an MIC of 2 mg/L, but the PTAs were all low. The predicted risk of toxicity was high regardless of the applied toxicity targets. The Hartford nomogram provided adequate gentamicin exposure in critically ill patients with an MIC ≤ 1 mg/L by considering the combined PK/PD indices.

Effect of Early Electroacupuncture Combined with Enhanced Recovery after Surgery (ERAS) on Pain Perception and Dysfunction in Patients after Total Knee Arthroplasty (TKA).

Objective: A retrospective case-control study was performed to observe the effect and clinical significance of early electroacupuncture combined with enhanced recovery after surgery (ERAS) on pain perception and dysfunction after total knee arthroplasty (TKA). Methods: About 100 patients who diagnosed with TKA from February 2019 to April 2021 were enrolled in our hospital. The patients were arbitrarily assigned into control group and study group. The former group was cured with electroacupuncture in the early stage, and the latter group was intervened on the basis of early electroacupuncture combined with the concept of ERAS. The curative effect, the time of getting out of bed for the first time after operation, the time of postoperative rehabilitation, postoperative rehabilitation cost, pain score and knee joint function score, range of motion (ROM) of knee joint, low shear of whole blood viscosity, plasma viscosity, fibrinogen level, and postoperative complications were compared. Results: There exhibited no statistical difference in clinical data. In terms of the treatment effects, there were 27 cases of markedly effective, 22 cases of effective, and 1 case of ineffective in the study group, and the total effective rate was 98.00%; in the control group, 15 cases were markedly effective, 28 cases were effective, and 13 cases were ineffective, and the total effective rate was 86.00%. Compared to the control group, the total effective rate of the study group was higher (P < 0.05). And the first time to get out of bed and the postoperative rehabilitation time in the study group were lower. Compared to the control group (10113.42 ± 524.83) yuan, the postoperative rehabilitation cost in the study group (12401.71 ± 530.77) yuan was higher. In terms of the scores of VAS and HSS, there exhibited no remarkable difference before treatment (P > 0.05). After treatment, the VAS score lessened and the HSS score augmented the study group VAS score (1.76 ± 0.28); the score in the control group was lower compared to the control group (3.45 ± 0.36), and HSS scoring (83.48 ± 11.23) points higher compared to the control group (65.82 ± 10.44) points (P < 0.05). The ROM of knee joint augmented successively at the 1st, 2nd, 4th, and 8th week after treatment comparison between groups, the ROM of the knee joint in the study group at the 1st, 2nd, 4th, and 8th week was (49.47 ± 3.60)°, (64.38 ± 5.32)°, (86.93 ± 6.72)°, and (104.20 ± 9.11)°, is higher compared to the control group (46.53 ± 3.41)°, (61.52 ± 5.20)°, (78.42 ± 6.45)°, and (98.77 ± 8.67)° (P < 0.05). One day after operation, there exhibited no remarkable difference in whole blood viscosity low shear, plasma viscosity, and fibrinogen level (P > 0.05). However, there exhibited no remarkable difference in plasma viscosity and fibrinogen level at 1 day and 7 days after operation (P > 0.05). Seven days after operation, the whole blood viscosity, plasma viscosity, and fibrinogen in the study group were lower (P < 0.05). The probability of postoperative complications was compared. In the study group, there were 2 cases of limb swelling and pain, 1 case of joint stiffness, and no swelling and pain complicated with deep venous thrombosis, and the total incidence was 6.00%. In the control group, there were 5 cases of limb swelling and pain, 3 cases of joint stiffness, and 3 cases of swelling and pain complicated with deep venous thrombosis, with a total incidence of 22.00%. The incidence of adverse reactions in the study group was lower (χ 2 = 5.317 P < 0.05). Conclusion: Early electroacupuncture combined with ERAS is of positive significance to the patients after TKA, which can reduce the pain, enhance the function of the knee joint, and promote the ROM of the knee joint, and can effectively shorten the first time out of bed and postoperative rehabilitation time and reduce whole blood viscosity low shear, plasma viscosity, and fibrinogen level, but the overall rehabilitation cost is high, and clinical application should be combined with the actual situation of patients.

Circulating Plasma Epstein-Barr Virus DNA Load During the Follow-up Periods Predicts Recurrence and Metastasis in Nasopharyngeal Carcinoma.

BACKGROUND: Epstein-Barr virus DNA (EBV DNA) load has been identified as a prognostic factor in nasopharyngeal carcinoma (NPC), whereas the dynamic changes in the long period have not been explored. In this study, we evaluated EBV DNA kinetics and its role in the survival. METHODS: We conducted a retrospective review of 900 NPC patients. Plasma EBV DNA levels were measured at various time points after treatment. The correlations of EBV kinetics with recurrence and metastasis were analyzed. After stratifying patients according to the EBV results, survival was compared using Kaplan-Meier estimates. Twelve- and 24-month landmark analyses for overall survival (OS) data were performed according to the EBV groups. RESULTS: Patients with post-EBV of less than 2500 copies/mL achieved better survival than did those with higher ones. Furthermore, patients with continuously elevated EBV DNA expressed significantly poorer OS (hazard ratio [HR], 2.542, 95% confidence interval [CI], 2.077-3.111; P < 0.001), distant metastasis-free survival (HR, 2.970; 95% CI, 2.392-3.687; P < 0.001), locoregional-free survival (HR, 1.699; 95% CI, 1.072-2.692; P = 0.013), and progression-free survival (HR, 2.535; 95% CI, 1.987-3.233; P < 0.001) than did patients with continuously normal EBV or those with elevated levels at any time point. The 5-year OS with elevated EBV was lower than that of the remission group by using the 12- and 24-month landmark analysis. CONCLUSIONS: Elevated EBV DNA after treatment was a better predictive indicator of survival than the baseline concentrations. Furthermore, continuously elevated EBV DNA after treatment indicated recurrence, metastasis, and unfavorable prognosis for NPC. In addition, there were consistent patterns of EBV DNA kinetics during long-term follow-up, which warrant further study.

Lessons drawn from China and South Korea for managing COVID-19 epidemic: Insights from a comparative modeling study.

We conducted a comparative study of the COVID-19 epidemic in three different settings: mainland China, the Guangdong province of China and South Korea, by formulating two disease transmission dynamics models which incorporate epidemic characteristics and setting-specific interventions, and fitting the models to multi-source data to identify initial and effective reproduction numbers and evaluate effectiveness of interventions. We estimated the initial basic reproduction number for South Korea, the Guangdong province and mainland China as 2.6 (95% confidence interval (CI): (2.5, 2.7)), 3.0 (95%CI: (2.6, 3.3)) and 3.8 (95%CI: (3.5,4.2)), respectively, given a serial interval with mean of 5 days with standard deviation of 3 days. We found that the effective reproduction number for the Guangdong province and mainland China has fallen below the threshold 1 since February 8th and 18th respectively, while the effective reproduction number for South Korea remains high until March 2nd Moreover our model-based analysis shows that the COVID-19 epidemics in South Korean is almost under control with the cumulative confirmed cases tending to be stable as of April 14th. Through sensitivity analysis, we show that a coherent and integrated approach with stringent public health interventions is the key to the success of containing the epidemic in China and especially its provinces outside its epicenter. In comparison, we find that the extremely high detection rate is the key factor determining the success in controlling the COVID-19 epidemics in South Korea. The experience of outbreak control in mainland China and South Korea should be a guiding reference for the rest of the world.

Population Pharmacokinetics and Dosing Optimization of Gentamicin in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy.

PURPOSE: Appropriate gentamicin dosing in continuous renal replacement therapy (CRRT) patients remains undefined. This study aimed to develop a population pharmacokinetic (PK) model of gentamicin in CRRT patients and to infer the optimal dosing regimen for gentamicin. METHODS: Fourteen CRRT patients dosed with gentamicin were included to establish a population PK model to characterize the variabilities and influential covariates of gentamicin. The pharmacokinetic/pharmacodynamic (PK/PD) target attainment and risk of toxicity for different combinations of gentamicin regimens (3-7 mg/kg q24h) and CRRT effluent doses (30-50 mL/h/kg) were evaluated by Monte Carlo simulation. The probability of target attainment (PTA) was determined for the PK/PD indices of the ratio of drug peak concentration/minimum inhibitory concentration (Cmax/MIC > 10) and the ratio of area under the drug concentration-time curve/MIC over 24 h (AUC0-24h/MIC > 100), and the risk of toxicity was estimated by drug trough concentration thresholds (1 and 2 mg/L). RESULTS: A one-compartment model adequately described the PK characteristics of gentamicin. Covariates including body weight, age, gender, and CRRT modality did not influence the PK parameters of gentamicin based on our dataset. All studied gentamicin regimens failed to achieve satisfactory PTAs for pathogens with an MIC ≥2 mg/L. A good balance of PK/PD target attainment and risk of toxicity (>2 mg/L) was achieved under 7 mg/kg gentamicin q24h and 40 mL/kg/h CRRT dose for an MIC ≤1 mg/L. CRRT dose intensity had a significant impact on the target attainment of AUC0-24h/MIC >100 and risk of toxicity. CONCLUSION: A combination of 7 mg/kg gentamicin q24h and 40 mL/kg/h CRRT dose might be considered as a starting treatment option for CRRT patients, and drug monitoring is required to manage toxicity.

Genome-scale CRISPR-Cas9 knockout screening in hepatocellular carcinoma with lenvatinib resistance.

Lenvatinib is the first target drug approved for advanced hepatocellular carcinoma (HCC). However, the development of drug resistance is common, and the mechanisms of lenvatinib resistance and resistant targets in HCC are poorly understood. By using CRISPR/Cas9 library screening, we screened out two key resistance genes, neurofibromin 1(NF1), and dual specificity phosphatase 9 (DUSP9), as critical drivers for lenvatinib resistance in HCC. With RNAi knockdown and CRISPR/Cas9 knockout models, we further clarified the mechanisms by which NF1 loss reactivates the PI3K/AKT and MAPK/ERK signaling pathways, while DUSP9 loss activates the MAPK/ERK signaling pathways, thereby inactivating FOXO3, followed by degradation of FOXO3, finally induced lenvatinib resistance. We also screened out trametinib, a small molecule pathway inhibitor for MEK, that can be used to reverse resistance induced by NF1 and DUSP9 loss in HCC cells. Trametinib was still able to halt HCC growth even when NF1 was knocked out in mice. Collectively, the findings indicate that NF1 and DUSP9 takes critical role in lenvatinib resistance and may be novel specific targets and predictive markers for lenvatinib resistance in HCC.

The risk of future waves of COVID-19: modeling and data analysis.

After a major outbreak of the coronavirus disease (COVID-19) starting in late December 2019, there were no new cases reported in mainland China for the first time on March 18, 2020, and no new cases reported in Hong Kong Special Administrative Region on April 20, 2020. However, these places had reported new cases and experienced a second wave since June 11, 2020. Here we develop a stochastic discrete-time epidemic model to evaluate the risk of COVID-19 resurgence by analyzing the data from the beginning of the outbreak to the second wave in these three places. In the model, we use an input parameter to represent a few potential risks that may cause a second wave, including asymptomatic infection, imported cases from other places, and virus from the environment such as frozen food packages. The effect of physical distancing restrictions imposed at different stages of the outbreak is also included in the model. Model simulations show that the magnitude of the input and the time between the initial entry and subsequent case confirmation significantly affect the probability of the second wave occurrence. Although the susceptible population size does not change the probability of resurgence, it can influence the severity of the outbreak when a second wave occurs. Therefore, to prevent the occurrence of a future wave, timely screening and detection are needed to identify infected cases in the early stage of infection. When infected cases appear, various measures such as contact tracing and quarantine should be followed to reduce the size of susceptible population in order to mitigate the COVID-19 outbreak.

[The feasibility of zygomatic implant quad approach in patients with tooth agenesis: a radiographic analysis].

PURPOSE: The aim of this study was to analyze the feasibility of zygomatic implant quad approach in patients with tooth agenesis. METHODS: Based on the data from cone-beam CT (CBCT), twenty one patients with tooth agenesis who were planned to receive zygomatic implant quad approach were enrolled. The radiographic bone-to-implant contact (rBIC) of each zygomatic implant placed virtually in patients' zygomatic segment was measured. SPSS 25.0 software package was used for statistical analysis. RESULTS: Twenty patients' plans of zygomatic implant quad approach were completed (12 men and 8 women). A total of 80 zygomatic implants were placed virtually and the average rBIC of zygomatic segment was (13.85±3.29) mm. The rBIC values of 40 mesial zygomatic implants and 40 distal zygomatic implants were (13.80±3.74) mm and (13.90±2.81) mm, respectively(P>0.05). The average rBIC in male of 24 mesial zygomatic implants and 24 distal zygomatic implants were(14.21±4.08) mm and(14.31±3.18) mm, respectively, slightly higher than those in female of 16 mesial zygomatic implants and 16 distal zygomatic implants, which were (13.18±3.18) mm and (13.29±2.10) mm, respectively. There was no significant difference between the two groups (P>0.05). The average rBIC of 15 extra sinus zygomatic implants, 46 against sinus lateral wall zygomatic implants and 19 intra-sinus zygomatic implants were (16.27±2.95), (13.87±3.10) and (11.88±2.78) mm, respectively. There was significant difference between the extra sinus zygomatic implants and the other two(P<0.05). CONCLUSIONS: It is feasible to plan zygomatic implant quad approach for patients with tooth agenesis. Zygomatic implants can get adequate rBIC in zygomatic segment and to provide sufficient support and retention of the superstructure.

A novel prognostic model for angioimmunoblastic T-cell lymphoma: A retrospective study of 55 cases.

OBJECTIVE: To explore prognostic factors and develop an accurate prognostic prediction model for angioimmunoblastic T-cell lymphoma (AITL). METHODS: Clinical data from Chinese patients with newly diagnosed AITL were retrospectively analysed. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier method survival curves; prognostic factors were determined using a Cox proportional hazards model. The sensitivity and specificity of the predicted survival rates were compared using area under the curve (AUC) of receiver operating characteristic (ROC) curves. RESULTS: The estimated 5-year OS and PFS of 55 eligible patients with AITL were 22% and 3%, respectively. Multivariate analysis showed that the presence of pneumonia, and serous cavity effusions at initial diagnosis were significant prognostic factors for OS. Based on AUC ROC values, our novel prognostic model was superior to IPI and PIT based models and suggested better diagnostic accuracy. CONCLUSIONS: Our prognostic model based on pneumonia, and serous cavity effusions at initial diagnosis enabled a balanced classification of AITL patients into different risk groups.

Effects of medical resource capacities and intensities of public mitigation measures on outcomes of COVID-19 outbreaks.

BACKGROUND: The COVID-19 pandemic is complex and is developing in different ways according to the country involved. METHODS: To identify the key parameters or processes that have the greatest effects on the pandemic and reveal the different progressions of epidemics in different countries, we quantified enhanced control measures and the dynamics of the production and provision of medical resources. We then nested these within a COVID-19 epidemic transmission model, which is parameterized by multi-source data. We obtained rate functions related to the intensity of mitigation measures, the effective reproduction numbers and the timings and durations of runs on medical resources, given differing control measures implemented in various countries. RESULTS: Increased detection rates may induce runs on medical resources and prolong their durations, depending on resource availability. Nevertheless, improving the detection rate can effectively and rapidly reduce the mortality rate, even after runs on medical resources. Combinations of multiple prevention and control strategies and timely improvement of abilities to supplement medical resources are key to effective control of the COVID-19 epidemic. A 50% reduction in comprehensive control measures would have led to the cumulative numbers of confirmed cases and deaths exceeding 590,000 and 60,000, respectively, by 27 March 2020 in mainland China. CONCLUSIONS: Multiple data sources and cross validation of a COVID-19 epidemic model, coupled with a medical resource logistic model, revealed the key factors that affect epidemic progressions and their outbreak patterns in different countries. These key factors are the type of emergency medical response to avoid runs on medical resources, especially improved detection rates, the ability to promote public health measures, and the synergistic effects of combinations of multiple prevention and control strategies. The proposed model can assist health authorities to predict when they will be most in need of hospital beds and equipment such as ventilators, personal protection equipment, drugs, and staff.