Risk predictive model for the development of hepatocellular carcinoma before initiating long-term antiviral therapy in patients with chronic hepatitis B virus infection.

It is generally acknowledged that antiviral therapy can reduce the incidence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), there remains a subset of patients with chronic HBV infection who develop HCC despite receiving antiviral treatment. This study aimed to develop a model capable of predicting the long-term occurrence of HCC in patients with chronic HBV infection before initiating antiviral therapy. A total of 1450 patients with chronic HBV infection, who received initial antiviral therapy between April 2006 and March 2023 and completed long-term follow-ups, were nonselectively enrolled in this study. Least absolute shrinkage and selection operator (LASSO) and Cox regression analysis was used to construct the model. The results were validated in an external cohort (n = 210) and compared with existing models. The median follow-up time for all patients was 60 months, with a maximum follow-up time of 144 months, during which, 32 cases of HCC occurred. The nomogram model for predicting HCC based on GGT, AFP, cirrhosis, gender, age, and hepatitis B e antibody (TARGET-HCC) was constructed, demonstrating a good predictive performance. In the derivation cohort, the C-index was 0.906 (95% CI = 0.869-0.944), and in the validation cohort, it was 0.780 (95% CI = 0.673-0.886). Compared with existing models, TARGET-HCC showed promising predictive performance. Additionally, the time-dependent feature importance curve indicated that gender consistently remained the most stable predictor for HCC throughout the initial decade of antiviral therapy. This simple predictive model based on noninvasive clinical features can assist clinicians in identifying high-risk patients with chronic HBV infection for HCC before the initiation of antiviral therapy.

Association between frozen embryo transfer and childhood allergy: a retrospective cohort study.

RESEARCH QUESTION: Does frozen embryo transfer (FET) increase the risk of allergic diseases in offspring? DESIGN: This study followed up 653 singleton children: 166 born through FET and 487 born through natural conception. Demographic characteristics, perinatal information and allergic diseases of children and their parents were collected through clinical medical systems and questionnaires. Among these 653 children, allergen-specific immunoglobulin E (IgE) testing was performed using peripheral blood samples collected from 207 children: 145 in the FET group and 62 in the natural conception group. The prevalence of allergic diseases and positive rates of allergen-specific IgE testing were compared between the two groups with adjustments for confounding factors. RESULTS: The prevalence of food allergy was significantly higher in children born through FET compared with children born through natural conception (adjusted OR = 3.154, 95% CI 1.895-5.250; P < 0.001). In addition, positive rates of food allergen sensitization were higher in children in the FET group compared with children in the natural conception group (adjusted OR = 5.769, 95% CI 2.859-11.751, P < 0.001). Children in the FET group had a higher positive sensitization rate to at least one allergen compared with children in the natural conception group (adjusted OR = 3.127, 95% CI 1.640-5.961, P < 0.001). No association was observed between FET and other allergic diseases, including asthma (P = 0.136), atopic dermatitis (P = 0.130) and allergic rhinitis (P = 0.922). Allergen sensitization IgE testing indicated no differences between the two groups in terms of positive sensitization rates of other common allergens, including animal and insect allergens (P = 0.627), inhaled outdoor allergens (P = 0.915) and inhaled outdoor allergens (P = 0.544). CONCLUSION: This study suggests that children born through FET have increased risk of developing food allergy in early childhood.

Physical activity changes and related factors in chronic heart failure patients during the postdischarge transition period: a longitudinal study.

BACKGROUND: Physical activity (PA) is essential and effective for chronic heart failure (CHF) patients. A greater understanding of the longitudinal change in PA and its influencing factors during the postdischarge transition period may help create interventions for improving PA. The aims of this study were (1) to compare the change in PA, (2) to examine the influencing factors of PA change, and (3) to verify the mediating pathways between influencing factors and PA during the postdischarge transition period in CHF patients. METHODS: A total of 209 CHF patients were recruited using a longitudinal study design. The Chinese version of the International Physical Activity Questionnaire (IPAQ), Patient-reported Outcome Measure for CHF (CHF-PRO), and the Chinese version of the Tampa Scale for Kinesiophobia Heart (TSK-Heart) were used to assess PA, CHF-related symptoms, and kinesiophobia. The IPAQ score was calculated (1) at admission, (2) two weeks after discharge, (3) two months after discharge, and (4) three months after discharge. Two additional questionnaires were collected during admission. Generalized estimating equation (GEE) models were fitted to identify variables associated with PA over time. We followed the STROBE checklist for reporting the study. RESULTS: The PA scores at the four follow-up visits were 1039.50 (346.50-1953.00) (baseline/T1), 630.00 (1.00-1260.00) (T2), 693.00 (1-1323.00) (T3) and 693.00 (160.88-1386.00) (T4). The PA of CHF patients decreased unevenly, with the lowest level occurring two weeks after discharge, and gradually improving at two and three months after discharge. CHF-related symptoms and kinesiophobia were significantly associated with changes in PA over time. Compared with before hospitalization, an increase in CHF-related symptoms at two weeks and two months after discharge was significantly associated with decreased PA. According to our path analysis, CHF-related symptoms were positively and directly associated with kinesiophobia, and kinesiophobia was negatively and directly related to PA. Moreover, CHF-related symptoms are indirectly related to PA through kinesiophobia. CONCLUSION: PA changed during the postdischarge transition period and was associated with CHF-related symptoms and kinesiophobia in CHF patients. Reducing CHF-related symptoms helps improve kinesiophobia in CHF patients. In addition, the reduction in CHF-related symptoms led to an increase in PA through the improvement of kinesiophobia. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (11/10/2022 ChiCTR2200064561 retrospectively registered).

Latest guideline of endoscopic submucosal dissection of early gastric cancer may not be suitable for Chinese patients: retrospective study findings from two centers.

BACKGROUND: To analyze the diagnostic efficiency of the four absolute endoscopic submucosal dissection (ESD) indications for lymph node metastasis (LNM) of Chinese patients with early gastric cancer (EGC). METHODS: We retrospectively analyzed EGC patients who underwent radical D2 gastrectomy from January 2019 to December 2022. We evaluated the rate of LNM, false-negative rate, and negative predictive value of the four ESD indications. RESULTS: Of enrolled 2722 EGC patients, 388 (14.3%) patients presented LNM. Tumor size > 2 cm, ulceration, submucosal invasion, undifferentiated type, and lymphovascular invasion were independent risk factors of LNM in patients with EGC. 1062 (39%) cases of EGC conformed to the four EDS indications; however, 4% of them had LNM. 451 cases were fully in accord with the fourth ESD indication (undifferentiated intramucosal carcinoma without ulceration and a maximum lesion diameter of ≤ 2 cm), and 35 of them had LNM, with a false-negative rate (FNR) of 9.02% and a negative predictive value (NPV) of 92.24%. There was significant difference among the four indications in terms of the rate of LNM (1.0% vs 1.5% vs 1.3% vs 7.8%, P < 0.001), FNR (1.03% vs 0.52% vs 0.26% vs 9.02%, P < 0.001), and NPV (98.99% vs 98.53% vs 98.75% vs 92.24%, P < 0.001). CONCLUSION: Overall, the fourth ESD indication was associated with a high rate of LNM compared to the other three indications. Thus, it might not be safe to classify it as an absolute indication in Chinese patients with EGC.

Evidence of microbiota-host dysbiosis between periodontitis and cerebral small vessel disease.

OBJECTIVES: To investigate the correlation between periodontitis and cerebral small vessel disease (CSVD) from the clinical and microbiological aspects. SUBJECTS AND METHODS: Periodontitis patients (CP group, n = 31) and CSVD patients (CSVD group, n = 30) were examined for neurological and periodontal condition. Subgingival plaque was collected and performed using 16S rRNA sequencing. Logistic regression and LASSO regression were used to analyze the periodontal parameters and subgingival microbiota related to CSVD, respectively. Inflammatory factors in gingival crevicular fluid (GCF) were also detected and compared between the two groups. RESULTS: Clinical attachment level (CAL), teeth number and plaque index demonstrated a significant difference between CP and CSVD group, meanwhile, CAL was independently associated with CSVD. Besides, the microbial richness and composition were distinct between two groups. Five genera related to periodontal pathogens (Treponema, Prevotella, Streptococcus, Fusobacterium, Porphyromonas) were screened out by LASSO regression, suggesting a potential association with CSVD. Finally, the levels of inflammatory factors in GCF were statistically higher in CSVD group than those in CP group. CONCLUSIONS: Cerebral small vessel disease patients demonstrated worse periodontal condition, meanwhile the interaction between microbiota dysbiosis and host factors (inflammation) leading to a better understanding of the association between periodontitis and CSVD.

Multi-omics profiling of papillary thyroid microcarcinoma reveals different somatic mutations and a unique transcriptomic signature.

BACKGROUND: Papillary thyroid microcarcinoma (PTMC) incidence has significantly increased, and some cases still exhibit invasive traits. The entire molecular landscape of PTMC, which can offer hints for the etiology of cancer, is currently absent. METHODS: We compared our findings with those for PTMC in the TCGA by analyzing the largest study at the current stage of whole exome sequencing and RNA-sequencing data from 64 patients with PTMC. Then, we systematically demonstrated the differences between the two PTMC subtypes based on multi-omics analyses. Additionally, we created a molecular prediction model for the PTMC subtypes and validated them among TCGA patients for individualized integrative assessment. RESULTS: In addition to the presence of BRAF mutations and RET fusions in the TCGA cohort, we also discovered a new molecular signature named PTMC-inflammatory that implies a potential response to immune intervention, which is enriched with AFP mutations, IGH@-ext fusions, elevated immune-related genes, positive peroxidase antibody, and positive thyroglobulin antibody. Additionally, a molecular prediction model for the PTMC-inflammatory patients was created and validated among TCGA patients, while the prognosis for these patients is poor. CONCLUSIONS: Our findings comprehensively define the clinical and molecular features of PTMC and may inspire new therapeutic hypotheses.

D-Limonene inhibits the occurrence and progression of LUAD through suppressing lipid droplet accumulation induced by PM2.5 exposure in vivo and in vitro.

BACKGROUND: PM2.5 exposure is associated with lung adenocarcinoma (LUAD), but the mechanism is unclear. The lack of understanding impedes our effort on prevention. This study examined a possible mechanism of lung cancer caused by PM2.5 exposure, and aimed to find a potential intervention for people living in PM2.5 polluted regions. METHODS: Electron microscopy and oil-red staining were conducted to examine the lipid droplet accumulation. Masson's trichrome staining, colony forming, scratch assay and transwell experiment were conducted to evaluate the effect of PM2.5 exposure and D-limonene intervention on the occurrence and progression of LUAD. Potential intervention targets were found by RNA-Seq and verified by luciferase reporter assay. MiR-195 KO mice constructed with CRISPR/Cas9 technology were used to investigate the pivotal role of D-limonene-miR-195-SREBP1/FASN axis. Cohort analysis of lung cancer patients, human LUAD tissues staining and human intervention trial were also conducted to validate the results of cell and animal experiments. RESULTS: Our results showed that PM2.5 exposure induced accumulation of lipid droplets in LUAD cells which accompanied by increased malignant cellular behaviors. PM2.5 exposure led to cleaved N-SREBP1 translocation into nucleus, which activated the de novo lipogenesis pathway. Same changes were also observed in normal lung epithelial cells and normal lung tissue, and mice developed pulmonary fibrosis after long-term exposure to PM2.5. Furthermore, in a cohort of 11,712 lung cancer patients, significant lipid metabolism disorders were observed in higher PM2.5 polluted areas. In view of that, D-limonene was found to inhibit the changes in lipid metabolism through upregulating the expression of miR-195, which inhibited the expression of lipogenic genes (SREBF1/FASN/ACACA) specifically. And a small human intervention trial showed that serum miR-195 was upregulated after oral intake of D-limonene. CONCLUSION: Our findings reveal a new mechanism of pulmonary fibrosis and LUAD that is related to PM2.5 exposure-induced lipid droplet accumulation. We also demonstrate that D-limonene-miR-195-SREBP1/FASN axis is a potential preventive intervention for mediating the progression and development of LUAD induced by PM2.5 exposure. Trial registration Chinese Clinical Trial Registry, ChiCTR2000030200. Registered 25 February 2020, http://www.chictr.org.cn/showproj.aspx?proj=48013.

Addition of sintilimab to nanoparticle albumin-bound paclitaxel and S-1 as adjuvant therapy in stage IIIC gastric cancer.

The prognosis of stage III gastric cancer (GC) is not satisfying and the specific chemotherapy regimens for GC of stage IIIC based on the 8th edition of the UICC/AJCC TNM staging system are still inconclusive. Peritoneal recurrence is the common and severe relapse pattern. Nanoparticle albumin-bound paclitaxel (Nab-PTX) is safer and more effective than PTX in the peritoneal metastasis. Clinical trial has demonstrated the safety and efficacy of sintilimab in GC. A combination of Nab-PTX, S-1 and sintilimab could be a promising triplet regimen as adjuvant therapy for GC. The aim of this article is to describe the design of this prospective Dragon-VII trial, conducted to evaluate the safety and efficacy of the combination of Nab-PTX, S-1 and sintilimab. Clinical trial registration: NCT04781413.

Lay abstract The prognosis of stage IIIC gastric cancer is poor and the treatment for it is not satisfying. This is a clinical trial that aims to explore a more effective therapy in gastric cancer patients of stage IIIC. Patients with stage IIIC gastric cancer must meet all of the inclusion criteria and none of the exclusion criteria to be eligible for this trial. The eligible patients will be given eight cycles of combinatory therapy of albumin-bound paclitaxel, a chemotherapy (day 1 and day 8), and S-1, another chemotherapy (days 1 to 14), plus sintilimab, a type of immunotherapy called an immune checkpoint inhibitor (day 1) every 3 weeks and then sintilimab maintenance for up to 12 months.

Serum sTREM-1 in adult-onset Still's disease: a novel biomarker of disease activity and a potential predictor of the chronic course.

OBJECTIVES: Triggering receptor expressed on myeloid cells-1 (TREM-1) is an amplifier of inflammatory signals. Recently, a soluble form of TREM-1 (sTREM-1) was described. This study aimed to investigate the role of serum sTREM-1 in patients with adult-onset Still's disease (AOSD). METHODS: Serum sTREM-1 levels were detected in 108 AOSD patients, 88 RA patients and 112 healthy controls (HC). The correlations of sTREM-1 with disease activity, clinical characteristics and laboratory parameters in AOSD patients were analysed by the Spearman correlation test. Risk factors for the chronic course of AOSD were evaluated by multivariate logistic regression analysis. RESULTS: AOSD patients had significantly higher serum sTREM-1 levels than RA patients and HC, and serum sTREM-1 levels were correlated with the systemic score, ferritin, leucocyte count, CRP, IL-1ß and IL-6. The elevation in the initial sTREM-1 level by itself could discriminate patients developing the chronic course from patients developing the nonchronic course. Moreover, an elevated sTREM-1 level (> 526.4475 pg/ml) was an independent risk factor for the chronic course in active AOSD patients. Furthermore, interfering with TREM-1 engagement led to reductions in the secretion of pro-inflammatory cytokines, such as IL-1ß, IL-6 and TNF-α, in neutrophils and monocytes from active AOSD patients. CONCLUSION: Serum sTREM-1 levels are correlated with disease activity, and an elevation in the initial serum sTREM-1 level is a potential predictor of the chronic course in AOSD patients, which currently provides the best predictive model for identifying patients prone to developing the chronic course of AOSD.

Prognosis and rescue therapy for sepsis-related severe thrombocytopenia in critically ill patients.

Sepsis is the most common critical disease with high mortality in intensive care unit. Platelet count (PC) frequently altered in sepsis patients and implicated in the pathogenesis of multi-organ failure. It is also worth mentioning that thrombocytopenia was closely associated with poor outcomes in sepsis patients. However, whether drug intervention aimed at correcting thrombocytopenia would improve the prognosis of sepsis patients and which kind of sepsis patients could benefit from this therapy is still unclear. This study aims to explore the effect of severe thrombocytopenia on the prognosis of sepsis and the impact of a platelet-elevating drug (recombinant human thrombopoietin, rhTPO) for these sepsis patients. In this study, we included 249 sepsis patients diagnosed by sepsis 3.0, and these patients were classified into the three groups based on PC: normal (PC ≥ 100 × 109/L), mild-moderate thrombocytopenia (50 × 109/L ≤ PC < 100 × 109/L), and severe thrombocytopenia (PC < 50 × 109/L). We found that patients with severe thrombocytopenia had more blood transfusion, shorter days free from organ support, and worse outcomes as compared with the normal group. However, there was no significant difference between normal and mild-moderate thrombocytopenia groups. Furthermore, a subgroup analysis showed that rescue therapy with rhTPO could rapidly lead to a recovery of the PC, prolong days free from organ support, increase survival days, and reduce the 28-day mortality in sepsis patients with severe thrombocytopenia. These results suggested that sepsis patients with severe thrombocytopenia, not mild-moderate thrombocytopenia, had a poorer prognosis. RhTPO, probably as effective rescue therapy, could quickly recover PC and improve the prognosis in these sepsis patients.

Lipid metabolism gene-wide profile and survival signature of lung adenocarcinoma.

BACKGROUND: Lung cancer has high morbidity and mortality across the globe, and lung adenocarcinoma (LUAD) is the most common histologic subtype. Disordered lipid metabolism is related to the development of cancer. Analysis of lipid-related transcriptome helps shed light on the diagnosis and prognostic biomarkers of LUAD. METHODS: In this study, expression analysis of 1045 lipid metabolism-related genes was performed between LUAD tumors and normal tissues derived from the Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) cohort. The interaction network of differentially expressed genes (DEGs) was constructed to identify the hub genes. The association between hub genes and overall survival (OS) was evaluated and formed a model to predict the prognosis of LUAD using a nomogram. The model was validated by another cohort, GSE13213. RESULTS: A total of 217 lipid metabolism-related DEGs were detected in LUAD. Genes were significantly enriched in glycerophospholipid metabolism, fatty acid metabolic process, and eicosanoid signaling. Through network analysis and cytoHubba, 6 hub genes were identified, including INS, LPL, HPGDS, DGAT1, UGT1A6, and CYP2C9. High expression of CYP2C9, UGT1A6, and INS, and low expressions of DGAT1, HPGDS, and LPL, were associated with worse overall survival for 1925 LUAD patients. The model showed that the high-risk score group had a worse OS, and the validated cohort showed the same result. CONCLUSIONS: In this study, a signature of 6 lipid metabolism genes was constructed, which was significantly associated with the diagnosis and prognosis of LUAD patients. Thus, the gene signature can be used as a biomarker for LUAD.

Analysis of the reduction in injury mortality disparity between urban and rural areas in developing China from 2010 to 2016.

BACKGROUND: Injuries are of growing public health concern in China, and the trends of urban-rural injury mortality disparity for the last decade are still being explored. This study aims to analyze trends in injury mortality disparity between urban and rural areas of China by region, sex, and age from 2010 to 2016. METHODS: Using data from the Disease Surveillance Points system (DSPs) collected by the Chinese Center for Disease Control and Prevention (CDC) from 2010 to 2016, injury age-standardized mortality rates (ASMRs) and rate ratios (RRs) were calculated for different groups. Chi-square tests were used to compare differences in rates between urban and rural residents. The time trends of injury ASMRs were assessed via the annual percentage change (APC), and RRs were used to analyze urban-rural mortality disparity. RESULTS: The crude injury mortality rate of rural areas was 1.5 times higher than that of urban areas. The urban-rural RR of injury ASMR decreased from 1.8 to 1.5 (APC = 5.0%) over time, from 2.0 to 1.7 (APC = 4.7%) for eastern regions, from 1.9 to 1.5 (APC = 5.4%) and from 1.6 to 1.3 (APC = 4.5%) among males and females, respectively. Further decreases were from 2.0 to 1.4 (APC = 7.8%), from 1.9 to 1.6 (APC = 6.4%), and from 1.8 to 1.2 (APC = 5.7%) in the 5-14, 45-64, and 65+ year age groups, respectively. The urban-rural RRs of ASMRs for fall, drowning and suicide decreased from 1.3 to 1.2 (APC = - 3.0%), from 2.3 to 1.6 (APC = - 13.8%) and from 2.1 to 1.6 (APC = - 9.9%,), respectively. CONCLUSIONS: The urban-rural injury mortality disparity was large, but showed a significant decreasing trend in China. Residents of eastern regions, males/females, 5-14/45+ year age groups in the urban-rural injury mortality disparity all decreased gradually during the investigated period.

Associations between Work Experience and Betel Nut, Alcohol, or Tobacco Use among Low-Income Taiwanese Students from Middle School to University.

Background: Research suggests that young working students are at higher risk for substance use. However, most studies have focused on students from middle-class families, with few investigations conducted on substance use by students from low-income families. Objective: To examine the associations between work experience and betel nut, alcohol, or tobacco (BAT) use among Taiwanese students from low-income families. Methods: The data for this cross-sectional study were derived from the fourth wave of the Taiwan Panel Study of Children and Youth survey which provides primary data on low-income families. A total of 3,350 low-income students aged 12-25 years old from middle school to university participated. The χ2 test was performed to examine differences in sociodemographic characteristics and BAT use between employed and unemployed students. Multivariate logistic regression was used to examine the associations between work status, work intensity, monthly income, occupation, and BAT use. Results: Employed students displayed higher BAT use than those who were unemployed. Increased BAT use was also associated with higher work intensity (except for betel nut use), higher monthly income, and specific occupations (such as service or manual work). Conclusions: Employment is independently associated with a higher risk of BAT use among low-income Taiwanese students. Work intensity and specific occupational fields may offer insights into formulating relevant preventive measures for these students.

Using Research Electronic Data Capture for Longitudinal Assessment Among Older Adults With Diabetes Enhances Real-Time Data Collection.

The aim of this study was to provide evidence on the application of Research Electronic Data Capture for collecting repeated data during a 7-day period among older adults. Fifty-seven adults (≥50 years) with type 2 diabetes were recruited. Participants completed one sleep diary upon awaking and one self-care diary before going to bed each day for 7 days. The diaries were administered via the Research Electronic Data Capture Web-based system and were completed via participants' own electronic devices. Objective compliance rate, time used to complete each diary, and participant experience were described. Approximately 80% (n = 45) of the participants used Research Electronic Data Capture. Among these participants, the noncompliance rate ranged between 0% and 8.9% for the sleep diary and 0% and 13.1% for the self-care diary. Participants spent 4.2 to 8.7 minutes on the sleep diary and 3.5 to 7.1 minutes on the self-care diary. It took the participants a longer time to complete the diaries during the first day than during the following 6 days. Few participants reported technical issues or felt inconvenient or stressful with completing the Research Electronic Data Capture diaries. Overall, the compliance rates were high. Completing the diaries was not time-consuming and participants were largely satisfied with the Research Electronic Data Capture data collection. Research Electronic Data Capture has aided the longitudinal data collection. With adequate training, Research Electronic Data Capture is an efficient tool to collect repeated data among older adults and thus is recommended for future research.

Genome-wide profiling of miRNA expression patterns in tubal endometriosis.

MicroRNA (miRNA) expression profiles in tubal endometriosis (EM) are still poorly understood. In this study, we analyzed the differential expression of miRNAs and the related gene networks and signaling pathways in tubal EM. Four tubal epithelium samples from tubal EM patients and five normal tubal epithelium samples from uterine leiomyoma patients were collected for miRNA microarray. Bioinformatics analyses, including Ingenuity Pathway Analysis (IPA), Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) validation of five miRNAs was performed in six tubal epithelium samples from tubal EM and six from control. A total of 17 significantly differentially expressed miRNAs and 4343 potential miRNA-target genes involved in tubal EM were identified (fold change >1.5 and FDR-adjusted P value <0.05). IPA indicated connections between miRNAs, target genes and other gynecological diseases like endometrial carcinoma. GO and KEGG analysis revealed that most of the identified genes were involved in the mTOR signaling pathway, SNARE interactions in vesicular transport and endocytosis. We constructed an miRNA-gene-disease network using target gene prediction. Functional analysis showed that the mTOR pathway was connected closely to tubal EM. Our results demonstrate for the first time the differentially expressed miRNAs and the related signal pathways involved in the pathogenesis of tubal EM which contribute to elucidating the pathogenic mechanism of tubal EM-related infertility.

The effect of recombinant human thrombopoietin (rhTPO) on sepsis patients with acute severe thrombocytopenia: a study protocol for a multicentre randomised controlled trial (RESCUE trial).

BACKGROUND: Sepsis is still a common critical disease with high morbidity and mortality in intensive care unit. Despite published guidelines for sepsis, development of antibiotic therapy and advanced organ support technologies, the mortality of sepsis patients is still 25% or more. It is necessary to distinguish the subtypes of sepsis, and the targeted therapy for the patients need to be explored. Platelets have various biological functions in hemostasis and thrombosis, host defense, inflammatory/immune responses and tissue repair/regeneration. Moreover, severe thrombocytopenia or sustained thrombocytopenia was closely associated with multiply organ dysfunction and higher mortality in sepsis patients. The clinical therapies for thrombocytopenia are platelet transfusion and platelet-elevating drugs. However, platelet transfusion has many defects in clinical practice in sepsis patients, and the impact of platelet-elevating drugs for sepsis patients is still unclear. RESCUE trial is aim to explore the effect of a platelet-elevating drug, recombinant human thrombopoietin (rhTPO), as an effective rescue therapy on sepsis patients with acute severe thrombocytopenia. METHODS: It is a randomized, open-label, multi-center, controlled trial in 5 tertiary academic hospitals including medical, surgical or general ICUs. In this study, a total of 200 sepsis patients with severe thrombocytopenia will be randomly assigned in a 1:1 ratio to the control and rhTPO group. The patients will be followed up to 28 days after randomization. All patients in two groups receive the same treatment based on the guideline of Surviving Sepsis Campaign. Primary outcome is 28-day mortality. Secondary outcomes are the changes of PCs, blood transfusion, biomarkers of infection and organ function, days free from advanced organ support, drug-related adverse events, the length of ICU and hospital stay. DISCUSSION: RESCUE trial is the first randomized controlled trial to explore the impact of rhTPO for severe thrombocytopenia in sepsis patients diagnosed by sepsis-3.0 standard. Furthermore, RESCUE trial results will be of significant clinical value on the targeted therapy and add clinical evidence that rhTPO is an effective rescue therapy for these sepsis patients. TRIAL REGISTRATION: ClinicalTrials.gov : NCT02707497. Registered Date: March 3rd, 2016. Protocol Version 3. Protocol Date: January 25th, 2019.

Effects of PKM2 on global metabolic changes and prognosis in hepatocellular carcinoma: from gene expression to drug discovery.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumor that threatens global human health. High PKM2 expression is widely reported in multiple cancers, especially in HCC. This study aimed to explore the effects of PKM2 on global gene expression, metabolic damages, patient prognosis, and multiple transcriptional regulation relationships, as well as to identify several key metabolic genes and screen some small-molecule drugs. METHODS: Transcriptome and clinical HCC data were downloaded from the NIH-GDC repository. Information regarding the metabolic genes and subsystems was collected from the Recon 2 human metabolic model. Drug-protein interaction data were obtained from the DrugBank and UniProt databases. We defined patients with PKM2 expression levels ≥11.25 as the high-PKM2 group, and those with low PKM2 expression (< 11.25) were defined as the low-PKM2 group. RESULTS: The results showed that the global metabolic gene expression levels were obviously divided into the high- or low-PKM2 groups. In addition, a greater number of affected metabolic subsystems were observed in the high-PKM2 group. Furthermore, we identified 98 PKM2-correlated deregulated metabolic genes that were associated with poor overall patient survival. Together, these findings suggest more comprehensive influences of PKM2 on HCC. In addition, we screened several small-molecule drugs that target these metabolic enzymes, some of which have been used in antitumor clinical studies. CONCLUSIONS: HCC patients with high PKM2 expression showed more severe metabolic damage, transcriptional regulation imbalance and poor prognosis than low-PKM2 individuals. We believe that our study provides valuable information for pathology research and drug development for HCC.

Effects of Prophylactic Ankle Supports on Vertical Ground Reaction Force During Landing: A Meta-Analysis.

There has been much debate on how prophylactic ankle supports (PASs) may influence the vertical ground reaction force (vGRF) during landing. Therefore, the primary aims of this meta-analysis were to systematically review and synthesize the effect of PASs on vGRF, and to understand how PASs affect vGRF peaks (F1, F2) and the time from initial contact to peak loading (T1, T2) during landing. Several key databases, including Scopus, Cochrane, Embase, PubMed, ProQuest, Medline, Ovid, Web of Science, and the Physical Activity Index, were used for identifying relevant studies published in English since inception to April 1, 2015. The computerized literature search and cross-referencing the citation list of the articles yielded 3,993 articles. Criteria for inclusion required that 1) the study was conducted on healthy adults; 2) the subject number and trial number were known; 3) the subjects performed landing with and without PAS; 4) the landing movement was in the sagittal plane; 5) the comparable vGRF parameters were reported; and 6) the F1 and F2 must be normalized to the subject's body weight. After the removal of duplicates and irrelevant articles, 6, 6, 15 and 11 studies were respectively pooled for outcomes of F1, T1, F2 and T2. This study found a significantly increased F2 (.03 BW, 95% CI: .001, .05) and decreased T1 (-1.24 ms, 95% CI: -1.77, -.71) and T2 (-3.74 ms, 95% CI: -4.83, -2.65) with the use of a PAS. F1 was not significantly influenced by the PAS. Heterogeneity was present in some results, but there was no evidence of publication bias for any outcome. These changes represented deterioration in the buffering characteristics of the joint. An ideal PAS design should limit the excessive joint motion of ankle inversion, while allowing a normal range of motion, especially in the sagittal plane. Key pointsPAS can effectively protect the ligamentous structure from spraining by providing mechanical support and cutaneous proprioceptive benefits.Using of PAS can significantly elevate F2 and reduce T1 and T2 during landing. These changes represented deterioration in the buffering characteristics of the joint.An ideal PAS design should limit the excessive joint motion of the ankle inversion, while allow normal range of motion, especially in the sagittal plane.

[Relationship between environmental tobacco smoke and lung cancer risk among nonsmokers in China: A meta-analysis].

OBJECTIVE: To investigate the relationship between the environmental tobacco smoke (ETS) and lung cancer by Meta-analysis. METHODS: We used "lung cancer/lung neoplasm", "non-smoking/non-smoker", "China/Chinese", "case-control/case control", "risk factor", "environmental tobacco smoke/passive smoking" as key words, to search papers in databases including Chinese BioMedical Literature (CBM), China National Knowledge Internet (CNKI), Wanfang, Vip Citation Databases (VIP), PubMed and Web of Science databases, and collected the case-control studies on ETS and lung cancer among Chinese non-smokers from January 1999 to December 2013. A total of 129 research papers were collected. RevMan 5.2 software was used to calculate combined odds radio (OR) and 95% CI. RESULTS: Qualified 18 literatures were included, total cases 6 145 and controls 8 132. Consolidated results showed that ETS exposure could increase the risk of lung cancer, combined OR (95% CI) = 1.52 (1.42-1.64). Stratified analysis showed that ETS exposure was found to be significantly associated with an increasing risk of the lung cancer on non-smoking women and men, and combined OR (95% CI) were 1.58 (1.42-1.75) and 1.34 (1.08-1.65), respectively; the ETS exposure from family or the working environment could increase the risk of lung cancer, and combined OR (95% CI) were 1.48 (1.20-1.82) and 1.38 (1.13-1.69) respectively; childhood exposure and adult exposure were no significant statistical significance, and combined OR (95% CI) were 1.37 (0.98-1.91), and 1.34 (0.97-1.85) respectively. CONCLUSION: Environmental tobacco smoke exposure was a significant risk factor of lung cancer among non-smokers in China.

Age-related wall shear stress changes assessed by vascular vector flow mapping in the carotid arteries of healthy adults: a cross-sectional study.

Background: Wall shear stress (WSS) is related to the pathogenesis of atherosclerosis. WSS is affected by a variety of hemodynamic factors, and there is still a lack of accurate and objective methods for measuring it. This study sought to evaluate hemodynamic changes in WSSmaximum (max), WSSmean, WSSminimum (min) in the common carotid artery of healthy adults of different ages using vascular vector flow mapping (VFM). Methods: A retrospective analysis was conducted on 70 healthy volunteers aged 20-89 years who were recruited from our Ultrasound Department between February 2021 and June 2021. An ultrasound system with a 3-15 MHz probe was used to determine regions of interest (ROIs) of the common carotid artery. VFM-based WSS measurements were obtained by selecting ROIs with optimal image quality from three full cardiac cycles. The participants were divided into the following seven age groups: the 20s group, the 30s group, the 40s group, the 50s group, the 60s group, the 70s group, and the 80s group. The WSS parameters were compared among the age groups. An analysis of variance or a Kruskal-Wallis test was used to evaluate the difference among the groups, and a Pearson analysis and linear regression were used for the correlation and trend analysis. Results: The WSS parameters were quantified using vascular VFM software. The WSSmax, WSSmean, WSSmin differed among the age groups and gradually decreased with age, the elderly were significantly lower than the young. The Pearson correlation coefficient of the WSSmax and age was -0.556 (P<0.001), that of the WSSmean and age was -0.461 (P<0.001), and that of the WSSmin and age was -0.308 (P<0.001). The WSS parameters with age are negatively correlated the carotid intima-media thickness differed between the groups. Conclusions: The carotid WSSmax, WSSmean, WSSmin can be quantitatively and visually analyzed using the vascular VFM technique. In healthy adults of different ages, the carotid WSSmax, WSSmean, WSSmin decreased with age. Our findings about the normal values of carotid WSS maybe have clinical reference value for future studies.