Advantages of unilateral percutaneous kyphoplasty for osteoporotic vertebral compression fractures-a systematic review and meta-analysis.

Data from English randomized controlled trials comparing unilateral versus bilateral PKP for the treatment of OVCFs were retrieved and analyzed, and the results showed that unilateral PKP is a better choice for the treatment of patients with OVCFs, which will provide a reliable clinical rationale for the treatment of OVCFs. PURPOSE: To investigate the advantages of unilateral percutaneous kyphoplasty (PKP) for the treatment of osteoporotic vertebral compression fractures(OVCFs). METHODS: The systematic evaluation program met all program requirements (CRD 42023422383) by successfully passing the PROSPERO International Prospective Systematic Evaluation Registry. Researchers searched the references of English-language randomized controlled trials comparing unilateral and bilateral PKP for the treatment of osteoporotic vertebral compression fractures published between 2010 and 2023 and manually searched for known primary and review articles. The study statistically analyzed data from all the included literature, which primarily included time to surgery, visual pain score(VAS) and Oswestry disability index(ODI) at postoperative follow-up time points, polymethylmethacrylate (PMMA, bone cement) injection dose, cement leakage, radiation dose, and improvement in kyphotic angle. RESULTS: This meta-analysis searched 416 articles published from 2010 to 2023 based on keywords, and 18 articles were finally included in this study. The results of the forest plot showed that unilateral PKP operative time, amount of bone cement used, and radiation dose to the patient were significantly reduced (p < 0.01, p < 0.01, and p < 0.01, respectively), and unilateral and bilateral PKP had comparable cement leakage (p = 0.49, 95% CI = 0.58-1.30), and there was no significant difference in the kyphotic angle between unilateral and bilateral PKP (p = 0.42, 95% CI = - 2.29-0.96). During follow-up, there was no significant difference in pain relief between unilateral and bilateral PKP (p = 0.70, 95% CI = - 0.09-0.06), nor was there a significant difference in ODI (p = 0.27, 95% CI = - 0.35-1.24). CONCLUSIONS: There is no difference in clinical efficacy between unilateral PKP and bilateral PKP, but unilateral PKP has a shorter operative time, a lower incidence of cement leakage, a lower amount of cement, and a lower radiation dose to the patient and operator. Unilateral PKP is a better option for patients with OVCFs.

Genome-wide 5-hydroxymethylcytosines in circulating cell-free DNA as noninvasive diagnostic markers for gastric cancer.

BACKGROUND: 5-Hydroxymethylcytosine-enriched gene profiles and regions show tissue-specific and tumor specific. There is a potential value to explore cell-free DNA 5-hydroxymethylcytosine feature biomarkers for early gastric cancer detection. METHODS: A matched case‒control study design with 50 gastric cancer patients and 50 controls was performed to sequence the different 5-hydroxymethylcytosine modification features of cell free DNA. Significantly differential 5-hydroxymethylcytosine modification genes were identified to construct a gastric cancer diagnostic model. Data set from GEO was used as an external testing set to test the robustness of the diagnostic model. RESULTS: Accounting for more than 90% of 5-hydroxymethylcytosine peaks were distributed in the gene body in both the gastric cancer and control groups. The diagnostic model was developed based on five different 5-hydroxymethylcytosine modification genes, FBXL7, PDE3A, TPO, SNTG2 and STXBP5. The model could effectively distinguish gastric cancer patients from controls in the training (AUC = 0.95, sensitivity = 88.6%, specificity = 94.3%), validation (AUC = 0.87, sensitivity = 73.3%, specificity = 93.3%) and testing (AUC = 0.90, sensitivity = 81.9%, specificity = 90.2%) sets. The risk scores of the controls from the model were significantly lower than those of gastric cancer patients in both our own data (P < 0.001) and GEO external testing data (P < 0.001), and no significant difference between different TNM stage patients (P = 0.09 and 0.66). Furthermore, there was no significant difference between the healthy control and benign gastric disease patients in the testing set from GEO (P = 0.10). CONCLUSIONS: The characteristics of 5-hydroxymethylcytosine in cell free DNA are specific to gastric cancer patients, and the diagnostic model constructed by five genes' 5-hydroxymethylcytosine features could effectively identify gastric cancer patients.

Appraising associations between signature lipidomic biomarkers and digestive system cancer risk: novel evidences from a prospective cohort study of UK Biobank and Mendelian randomization analyses.

BACKGROUND: The roles of serum lipids on digestive system cancer (DSC) risk were still inconclusive. In this study, we systematically assessed indicative effects of signature lipidomic biomarkers (high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG)) on DSC (oesophagus, stomach, colorectal, liver, gallbladder, and pancreas cancers) risk. METHODS: HDL-C, LDL-C, and TG concentration measurements were respectively analyzed with enzyme immunoinhibition, enzymatic selective protection, and GPO-POD methods in AU5800 supplied from Beckman Coulter. The diagnoses of DSCs were coded using International Classification of Diseases, Tenth Revision (ICD-10) codes updated until October 2022 in the UK Biobank (UKB). In this study, we assessed phenotypic association patterns between signature lipidomic biomarkers and DSC risk using restricted cubic splines (RCSs) in multivariable-adjusted Cox proportional hazards regression models. Moreover, linear and nonlinear causal association patterns of signature lipidomic biomarkers with DSC risk were determined by linear and nonlinear Mendelian randomization (MR) analyses. RESULTS: A median follow-up time of 11.8 years was recorded for 319,568 participants including 6916 DSC cases. A suggestive independent nonlinear phenotypic association was observed between LDL-C concentration and stomach cancer risk (Pnonlinearity < 0.05, Poverall < 0.05). Meanwhile, a remarkable independent linear negative phenotypic association was demonstrated between HDL-C concentration and stomach cancer risk (Pnonlinearity > 0.05, Poverall < 0.008 (0.05/6 outcomes, Bonferroni-adjusted P)), and suggestive independent linear positive associations were observed between HDL-C concentration and colorectal cancer risk, and between TG concentration and gallbladder cancer risk (Pnonlinearity > 0.05, Poverall < 0.05). Furthermore, based on nonlinear and linear MR-based evidences, we observed an suggestive independent negative causal association (hazard ratio (HR) per 1 mmol/L increase: 0.340 (0.137-0.843), P = 0.020) between LDL-C and stomach cancer risk without a nonlinear pattern (Quadratic P = 0.901, Cochran Q P = 0.434). Meanwhile, subgroup and stratified MR analyses both supported the category of LDL-C ≥ 4.1 mmol/L was suggestively protective against stomach cancer risk, especially among female participants (HR: 0.789 (0.637-0.977), P = 0.030) and participants aged 60 years or older (HR: 0.786 (0.638-0.969), P = 0.024), and the category of TG ≥ 2.2 mmol/L concluded to be a suggestive risk factor for gallbladder cancer risk in male participants (HR: 1.447 (1.020-2.052), P = 0.038) and participants aged 60 years or older (HR: 1.264 (1.003-1.593), P = 0.047). CONCLUSIONS: Our findings confirmed indicative roles of signature lipidomic biomarkers on DSC risk, notably detecting suggestive evidences for a protective effect of high LDL-C concentration on stomach cancer risk, and a detrimental effect of high TG concentration on gallbladder cancer risk among given participants.

The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy.

Cancer, a disease that modern medicine has not fully understood and conquered, with its high incidence and mortality, deprives countless patients of health and even life. According to global cancer statistics, there were an estimated 19.3 million new cancer cases and nearly 10 million cancer deaths in 2020, with the age-standardized incidence and mortality rates of 201.0 and 100.7 per 100,000, respectively. Although remarkable advancements have been made in therapeutic strategies recently, the overall prognosis of cancer patients remains not optimistic. Consequently, there are still many severe challenges to be faced and difficult problems to be solved in cancer therapy today. Epigallocatechin gallate (EGCG), a natural polyphenol extracted from tea leaves, has received much attention for its antitumor effects. Accumulating investigations have confirmed that EGCG can inhibit tumorigenesis and progression by triggering apoptosis, suppressing proliferation, invasion, and migration, altering tumor epigenetic modification, and overcoming chemotherapy resistance. Nevertheless, its regulatory roles and biomolecular mechanisms in the immune microenvironment, metabolic microenvironment, and immunotherapy remain obscure. In this article, we summarized the most recent updates about the effects of EGCG on tumor microenvironment (TME), metabolic reprogramming, and anti-cancer immunotherapy. The results demonstrated EGCG can promote the anti-cancer immune response of cytotoxic lymphocytes and dendritic cells (DCs), attenuate the immunosuppression of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), and inhibit the tumor-promoting functions of tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), and various stromal cells including cancer-associated fibroblasts (CAFs), endothelial cells (ECs), stellate cells, and mesenchymal stem/stromal cells (MSCs). Additionally, EGCG can suppress multiple metabolic reprogramming pathways, including glucose uptake, aerobic glycolysis, glutamine metabolism, fatty acid anabolism, and nucleotide synthesis. Finally, EGCG, as an immunomodulator and immune checkpoint blockade, can enhance immunotherapeutic efficacy and may be a promising candidate for antitumor immunotherapy. In conclusion, EGCG plays versatile regulatory roles in TME and metabolic reprogramming, which provides novel insights and combined therapeutic strategies for cancer immunotherapy.

The crosstalk among the physical tumor microenvironment and the effects of glucose deprivation on tumors in the past decade.

The occurrence and progression of tumors are inseparable from glucose metabolism. With the development of tumors, the volume increases gradually and the nutritional supply of tumors cannot be fully guaranteed. The tumor microenvironment changes and glucose deficiency becomes the common stress environment of tumors. Here, we discuss the mutual influences between glucose deprivation and other features of the tumor microenvironment, such as hypoxia, immune escape, low pH, and oxidative stress. In the face of a series of stress responses brought by glucose deficiency, different types of tumors have different coping mechanisms. We summarize the tumor studies on glucose deficiency in the last decade and review the genes and pathways that determine the fate of tumors under harsh conditions. It turns out that most of these genes help tumor cells survive in glucose-deprivation conditions. The development of related inhibitors may bring new opportunities for the treatment of tumors.

A 4.7-kDa polysaccharide from Panax ginseng suppresses Aß pathology via mitophagy activation in cross-species Alzheimer's disease models.

Alzheimer's disease (AD) is a neurological condition that progresses with age. Amyloid-ß (Aß) aggregation has been suggested to be a key pathogenic process in Alzheimer's disease. Ginseng polysaccharides (GP), the main biologically active components isolated from Panax ginseng C. A. Meyer (ginseng), may act as neuroprotective agents with potential benefits for AD patients. However, GP effects on Aß pathology and AD symptoms are still unclear. Here, a 4.7-kDa GP termed GP4 was purified and subjected to basic physicochemical characterization. The biological effects of GP4 to prevent Aß aggregation were then assessed with cross-species AD models, including Aftin-5-treated SH-SY5Y cells and cerebral organoids, and transgenic C. elegans overexpressing the full-length human Aß42 peptide. These analyses ultimately demonstrated that GP4 was capable of inhibiting Aß accumulation both in vivo and vitro, and with early intervention of GP4 being sufficient to alleviate Aß42-associated aging phenotypes and memory loss in C. elegans model of AD. Furthermore, neuroinflammation was significantly down-regulated in human cells and cerebral organoids. From a mechanistic perspective, the ability of GP4 to inhibit Aß aggregation was found to be related to its ability to promote neuronal mitophagic activity. This finding offers a robust theoretical foundation for the further development of GP4 as a candidate drugs with the potential to treat AD.

Risk-stratified approach by aMAP score for community population infected with hepatitis B and C to guide subsequent liver cancer screening practice: A cohort study with 10-year follow-up.

The aim of this study was to determine whether the age-Male-ALBI-Platelet (aMAP) score is applicable in community settings and how to maximise its role in risk stratification. A total of thousand five hundred and three participants had an aMAP score calculated at baseline and were followed up for about 10 years to obtain information on liver cancer incidence and death. After assessing the ability of aMAP to predict liver cancer incidence and death in terms of differentiation and calibration, the optimal risk stratification threshold of the aMAP score was explored, based on absolute and relative risks. The aMAP score achieved higher area under curves (AUCs) (almost all above 0.8) within 10 years and exhibited a better calibration within 5 years. Regarding absolute risk, the risk of incidence of and death from liver cancer showed a rapid increase after an aMAP score of 55. The cumulative incidence (5-year: 8.3% vs. 1.3% and 10-year: 20.9% vs. 3.6%) and mortality (5-year: 6.7% vs. 1.1% and 10-year: 17.5% vs. 3.1%) of liver cancer in individuals with an aMAP score of ≥55 were significantly higher than in those with a score of <55 (Grey's test p < .001). In terms of relative risk, the risk of death from liver cancer surpassed that from other causes after an aMAP score of ≥55 [HR = 1.38(1.02-1.87)]. Notably, the two types of death risk had opposite trends between the subpopulation with an aMAP score of ≥55 and < 55. To conclude, this study showed the value of the aMAP score in community settings and recommends using 55 as a new risk stratification threshold to guide subsequent liver cancer screening.

Anticancer therapeutic effect of ginsenosides through mediating reactive oxygen species.

Dysregulation of reactive oxygen species (ROS) production and ROS-regulated pathways in cancer cells leads to abnormal accumulation of reactive oxygen species, displaying a double-edged role in cancer progression, either supporting transformation/proliferation and stimulating tumorigenesis or inducing cell death. Cancer cells can accommodate reactive oxygen species by regulating them at levels that allow the activation of pro-cancer signaling pathways without inducing cell death via modulation of the antioxidant defense system. Therefore, targeting reactive oxygen species is a promising approach for cancer treatment. Ginsenosides, their derivatives, and related drug carriers are well-positioned to modulate multiple signaling pathways by regulating oxidative stress-mediated cellular and molecular targets to induce apoptosis; regulate cell cycle arrest and autophagy, invasion, and metastasis; and enhance the sensitivity of drug-resistant cells to chemotherapeutic agents of different cancers depending on the type, level, and source of reactive oxygen species, and the type and stage of the cancer. Our review focuses on the pro- and anticancer effects of reactive oxygen species, and summarizes the mechanisms and recent advances in different ginsenosides that bring about anticancer effects by targeting reactive oxygen species, providing new ideas for designing further anticancer studies or conducting more preclinical and clinical studies.

The potential of epigallocatechin gallate in the chemoprevention and therapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), one of the most notorious malignancies globally, has a high fatality and poor prognosis. Though remarkable breakthroughs have been made in the therapeutic strategies recently, the overall survival of HCC remains unsatisfactory. Consequently, the therapy of HCC remains a great challenge. Epigallocatechin gallate (EGCG), a natural polyphenol extracted from the leaves of the tea bush, has been extensively investigated for its antitumor effects. In this review, we summarize the previous literature to elucidate the roles of EGCG in the chemoprophylaxis and therapy of HCC. Accumulating evidence has confirmed EGCG prevents and inhibits the hepatic tumorigenesis and progression through multiple biological mechanisms, mainly involving hepatitis virus infection, oxidative stress, proliferation, invasion, migration, angiogenesis, apoptosis, autophagy, and tumor metabolism. Furthermore, EGCG enhances the efficacy and sensitivity of chemotherapy, radiotherapy, and targeted therapy in HCC. In conclusion, preclinical studies have confirmed the potential of EGCG for chemoprevention and therapy of HCC under multifarious experimental models and conditions. Nevertheless, there is an urgent need to explore the safety and efficacy of EGCG in the clinical practice of HCC.

Elder and booster vaccination associates with decreased risk of serious clinical outcomes in comparison of Omicron and Delta variant: A meta-analysis of SARS-CoV-2 infection.

Background: The COVID-19 pandemic brings great pressure to the public health systems. This meta-analysis aimed to compare the clinical outcomes among different virus variants, to clarify their impact on medical resources and to provide evidence for the formulation of epidemic prevention policies. Methods: A systematic literature search was performed in the PubMed, Embase, and Cochrane Library databases using the key words "Omicron" and "Delta." The adjusted Risk ratios (RRs), Odds ratios (ORs) and Hazard ratios (HRs) were extracted, and RRs and Rate difference % (RD%) were used to interpret the risk estimates of the outcomes ultimately. Results: Forty-three studies were included, with 3,812,681 and 14,926,841 individuals infected with SARS-CoV-2 Delta and Omicron variant, respectively. The relative risks of hospitalization, death, ICU admission, and mechanical ventilation use after infection with the Omicron variant were all significantly reduced compared those after infection with the Delta variant (RRhospitalization = 0.45, 95%CI: 0.40-0.52; RRdeath = 0.37, 95%CI: 0.30-0.45; RRICU = 0.35, 95%CI: 0.29-0.42; RRmechanical ventilation = 0.33, 95%CI: 0.25-0.44). The change of both absolute and relative risks for hospitalization was more evident (RR = 0.47, 95%CI: 0.42-0.53；RD% =10.61, 95%CI: 8.64-12.59) and a significant increase was observed for the absolute differences in death in the elderly (RD% = 5.60, 95CI%: 4.65-6.55); the change of the absolute differences in the risk of hospitalization and death were most markedly observed in the patients with booster vaccination (RD%hospitalization = 8.60, 95CI%: 5.95-11.24; RD%death = 3.70, 95CI%: 0.34-7.06). Conclusion: The ability of the Omicron variant to cause severe clinical events has decreased significantly, as compared with the Delta variant, but vulnerable populations still need to be vigilant. There was no interaction between the vaccination doses and different variants.

Roles of survival situation and personality temperament in the relationship between life stress and depression of higher vocational college students.

BACKGROUND: Higher vocational college students face more life stress, which can easily result in depression and hinder their healthy growth. This study aimed to explore the roles of survival situation and personality temperament in the relationship between life stress and depression. METHODS: A self-compiled "College Students' Life Stress and Mental Health Questionnaire" was used to survey 4800 students in a Chinese higher vocational college. The questionnaire consisted of five subscales: life stressors scale, stress response scale, depression scale, personality temperament types scale, and survival situations scale. The sample included 4705 students, of whom 3449 (73.30%) were males and 1256 (26.70%) were females, with 990 urban students (21.04%), 3715 rural students (78.96%). The age of the participants ranged from 17 to 33 years. The data were analyzed using SPSS v26, PROCESS v3.3, and AMOS v23. RESULTS: (1) The depression rate of higher vocational students was 18.10% (with a severe depression rate of 1.60%). Life stress could explain 43.80% of depressive episodes (p < 0.01), (2) Among survival situations, the depression degree and rate of students in adversity were the highest (M = 1.56, 24.10%), (3) Among temperament types, the depression degree and rate of melancholic students were the highest (M = 2.13, 36.05%), (4) Survival situation and personality temperament had significant moderating interaction effects on depression caused by life stress (p < 0.01), students in adversity and depressive temperament were more susceptible, (5) Survival situations moderated three paths of the "life stressors-stress response-depression" partial mediation model, and personality temperament types moderated "stress response-depression" path. CONCLUSION: Prosperity and sanguine temperament are protective factors of depression caused by life stress in higher vocational students. Dilemma, adversity and melancholic temperament are risk factors of depression caused by life stress in higher vocational students.

Genetic estimation of correlations and causalities between multifaceted modifiable factors and gastro-oesophageal reflux disease.

Background: Gastro-oesophageal reflux disease (GORD) is a common gastrointestinal dysfunction that significantly affects the quality of daily life, and health interventions are challenging to prevent the risk of GORD. In this study, we used Mendelian randomization framework to genetically determine the causal associations between multifaceted modifiable factors and the risk of GORD. Materials and methods: Sixty-six exposures with available instrumental variables (IVs) across 6 modifiable pathways were included in the univariable MR analysis (UVMR). Summary-level genome-wide association studies (GWAS) datasets for GORD were retrieved from the Neale Lab (GORD Neale , Ncases = 29975, Ncontrols = 390556) and FinnGen (GORD Finn , Ncases = 13141, Ncontrols = 89695). Using the METAL software, meta-analysis for single nucleotide polymorphisms (SNPs) from GORD Neale and GORD Finn was conducted with an inverse variance weighted (IVW) fixed-effect model. Moreover, we leveraged partition around medoids (PAM) clustering algorithm to cluster genetic correlation subtypes, whose hub exposures were conditioned for multivariable MR (MVMR) analyses. P-values were adjusted with Bonferroni multiple comparisons. Results: Significant causal associations were identified between 26 exposures (15 risk exposures and 11 protective exposures) and the risk of GORD. Among them, 13 risk exposures [lifetime smoking, cigarette consumption, insomnia, short sleep, leisure sedentary behavior (TV watching), body mass index (BMI), body fat percentage, whole body fat mass, visceral adipose tissue, waist circumference, hip circumference, major depressive disorder, and anxious feeling], and 10 protective exposures (leisure sedentary behavior (computer use), sitting height, hand grip strength (left and right), birth weight, life satisfaction, positive affect, income, educational attainment, and intelligence) showed novel significant causal associations with the risk of GORD. Moreover, 13 exposures still demonstrated independent associations with the risk of GORD following MVMR analyses conditioned for hub exposures (educational attainment, smoking initiation and BMI). In addition, 12 exposures showed suggestive causal associations with the risk of GORD. Conclusion: This study systematically elucidated the modifiable factors causally associated with the risk of GORD from multifaceted perspectives, which provided implications for prevention and treatment of GORD.

PTEN Expression Was Significantly Associated with PD-L1 Score but Not with EBV Infection in Gastric Cancer.

Purpose: Gastric cancer (GC) remains a prevalent aggressive tumor with high morbidity and mortality globally. The identification of GC subtypes based on molecular features improved the prediction of prognosis and the selection of targeted therapies. PTEN is a characteristic tumor suppressor, while its association with different GC subtypes was unknown. Patients and Methods: The cohort consisted of 248 patients diagnosed with gastric cancer who were hospitalized and received radical gastrectomy. In addition, PTEN gene expression matrix of STAD was retrieved from TCGA. The mRNA and protein levels of PTEN and PD-L1 were detected using qRT-PCR and IHC staining. Multivariate logistic regression and Kaplan-Meier analysis were used to examine the relationship between PTEN expression and clinical characteristics. Results: In our study, PTEN was downregulated in gastric tumors both in mRNA and protein levels. Its inactivation was closely linked to higher histological grade (P = 0.005), neural invasion (P = 0.012), depth of invasion (P = 0.021), lymph metastasis (P = 0.026), and TNM stage (P = 0.001) of GC in the present study. Moreover, according to the molecular subtypes, high PTEN expression was related to high TPS score of PD-L1 positively (P = 0.010) but was not associated with MSI and EBV infection. Further, TCGA data validated that PTEN was indeed correlated with histological grade and invasion depth and positively related to PD-L1 expression (R = 0.29, adjusted P < 0.001). Conclusion: The above results suggested that PTEN expression was a useful marker in gastric carcinogenesis and progression and in the selection of immunotherapy-based treatments for GC patients.

Increased 5-hydroxymethylcytosine is a favorable prognostic factor of Helicobacter pylori-negative gastric cancer patients.

BACKGROUND: Most gastric cancer (GC) patients are diagnosed at middle or late stage because the symptoms in early stage are obscure, which causes higher mortality rates of GC. Helicobacter pylori (H. pylori) was identified as a class I carcinogen and leads to aberrant DNA methylation/hydroxymethylation. 5-hydroxymethylcytosine (5-hmC) plays complex roles in gene regulation of tumorigenesis and can be considered as an activating epigenetic mark of hydroxymethylation. AIM: To explore the association between 5-hmC levels and the progression and prognosis of GC patients with or without H. pylori infection. METHODS: A retrospective cohort study was conducted to estimate the predicted value of 5-hmC level in the progression and prognosis of GC patients with different H. pylori infection status. A total of 144 GC patients were recruited. RESULTS: The levels of 5-hmC were significantly decreased in tumor tissues (0.076 ± 0.048) compared with the matched control tissues (0.110 ± 0.057, P = 0.001). A high level of 5-hmC was an independent significant favorable predictor of overall survival in GC patients (hazard ratio = 0.61, 95% confidence interval: 0.38-0.98, P = 0.040), the H. pylori-negative GC subgroup (hazard ratio = 0.30, 95% confidence interval: 0.13-0.68, P = 0.004) and the GC patients with TNM stage Ⅰ or Ⅱ (hazard ratio = 0.32, 95% confidence interval: 0.13-0.77, P = 0.011). CONCLUSION: Increased 5-hmC is a favorable prognostic factor in GC, especially for H. pylori-negative subgroups.

Hsa-miR-3202 attenuates Jurkat cell infiltration via MMP2 in primary Sjögren's syndrome.

BACKGROUND: Primary Sjögren's syndrome is characterized by lymphocytic infiltration and dysfunction of exocrine glands. The persistent presence of lymphocytes in these glands is an important cause of injury to glandular epithelial cells. MicroRNAs play an important role in primary Sjögren's syndrome and regulate mRNA expression. This study evaluated the expression of microRNA related to lymphocyte infiltration in primary Sjögren's syndrome patients so as to find novel diagnostic and therapeutic targets for primary Sjögren's syndrome. We also explored the microRNA-mRNA networks related to lymphocyte infiltration. METHODS: mRNA-seq and microRNA-seq of peripheral blood mononuclear cells (PBMCs) were performed on samples from five primary Sjögren's syndrome patients and five matched healthy controls. Meanwhile, microRNA-mRNA network analysis was also conducted. RT-qPCR was used for validation of differentially expressed RNAs. Immunohistochemistry analysis was used to detect MMP2 expression in labial gland tissue. Hsa-miR-3202 mimics/inhibitor-transfected Jurkat cells were used to measure the effects of hsa-miR-3202 on the infiltration potential of T cells. RESULTS: mRNA and microRNA sequencing revealed that 84 differentially expressed mRNAs and 49 differentially expressed microRNAs had a mutual regulatory relationship. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that differentially expressed MMP2 and its related microRNA, hsa-miR-3202, were enriched in the leukocyte transendothelial migration pathway. MMP2 was highly expressed in PBMC and labial gland tissue in primary Sjögren's syndrome patients. Hsa-miR-3202 was lower expressed in primary Sjögren's syndrome than healthy control. Furthermore, hsa-miR-3202 mimics transfection decreased MMP2 expression in Jurkat cells, and inhibited Jurkat cells invasion (p = 0.047). CONCLUSION: Large number of differentially expressed microRNAs and mRNAs were detected in primary Sjögren's syndrome, and these differentially expressed microRNAs and mRNAs had a mutual regulatory relationship and played an important role in primary Sjögren's syndrome. In the study, we found hsa-miR-3202 regulate MMP2 and inhibited the infiltration of T cells from peripheral blood into the gland, which played a protective role.

A scFv phage targeting the C. albicans cell wall screened from a bacteriophage-based library of induced immune protection in mice.

C. albicans is the most prevalent opportunistic fungal and can cause life-threatening systemic infections under certain circumstances. The inefficiency and resistance of traditional therapy make the development of novel techniques indispensable. The main components, proteins and glycoproteins, of the C. albicans cell wall are highly immunogenic and very different from those of the host, making it an ideal source of targets for antifungal drug development. This study aimed to screen and identify specific peptides that bind to the C. albicans cell wall using a phage-display peptide library, and to develop a peptide-based therapy targeted to C. albicans. After four rounds of screening, JC-1 ScFv was found to bind to the C. albicans cell wall specifically, inhibit C. albicans growth and viability in vitro, and protect mice from C. albicans infection in vivo. Further study showed that JC-1 could provoke an immune response in C. albicans-infected mice. These results indicated that JC-1 ScFv screened from a phage-display peptide library had the potential to be developed as a vector for targeting C. albicans.

Positive H. pylori status predicts better prognosis of non-cardiac gastric cancer patients: results from cohort study and meta-analysis.

BACKGROUND: Previous researches have associated Helicobacter pylori (H. pylori) with a prognosis of gastric cancer (GC), however, without a concert conclusion. This study aimed to study this issue further by a prospective cohort study and a meta-analysis. METHODS: Histologically diagnosed gastric cancer (GC) patients were recruited into the primary prospective cohort study between January 2009 to December 2013. All the patients were followed-up periodically to record information on post-surgery therapy and overall survival status. The pre-surgery status of H. pylori was measured by enzyme-linked immunosorbent assay. A meta-analysis was conducted after retrieving related researches in the databases of PubMed and Embase up to April 2020. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were summarized to validate the relationship between H. pylori infection and the survival time of GC patients. I2 statistics and Q test were used to assess the heterogeneity. Sensitivity analyses were performed using Galbraith's plot, leave-one-out analysis, subgroup analyses and meta-regression to explore the sources of heterogeneity and the stability of the summary results. RESULTS: A total of 743 GC patients with radical tumorectomy were included prospectively and 516 (69.4%) were positive on H. pylori. H. pylori-positive patients tended to survive longer than -negative ones (HR 0.92, 95%CI: 0.74-1.15), though the tendency was not statistically significant. Cohort studies on the prognosis of GC were retrieved comprehensively by assessing the full-text and 59 published studies, together with the result of our study, were included in the further meta-analysis. The summarized results related the positive status of H. pylori to better overall survival (HR 0.81, 95%CI: 0.72-0.90) and disease-free survival (HR 0.83, 95%CI: 0.67-0.99). Results from subgroup analyses indicated that the pooled magnitude of this association was relatively lower in studies not referring to H. pylori in title and abstract. CONCLUSIONS: In conclusion, gastric cancer patients with H. pylori have a better prognosis than patients of H. pylori negative. More stringent surveillance strategies may be necessary for patients with H. pylori negative at cancer diagnosis.

A new adaptive sliding mode controller based on the RBF neural network for an electro-hydraulic servo system.

Accuracy and robust trajectory tracking for electro-hydraulic servo systems in the presence of load disturbances and model uncertainties are of great importance in many fields. In this work, a new adaptive sliding mode control method based on the RBF neural networks (SMC-RBF) is proposed to improve the performances of a robotic excavator. Model uncertainties and load disturbances of the electro-hydraulic servo system are approximated and compensated using the RBF neural networks. Adaptive mechanisms are designed to adjust the connection weights of the RBF neural networks in real time to guarantee the stability. A nonlinear term is introduced into the sliding mode to design an adaptive terminal sliding mode control structure to improve dynamic performances and the convergence speed. Moreover, a sliding mode chattering reduction method is proposed to suppress the chattering phenomenon. Three types of step, ramp and sine signals are used as the simulation reference trajectories to compare different controllers on a co-simulation platform. Experiments with leveling and triangle conditions are presented on a robotic excavator. Results show that the proposed SMC-RBF controller is superior to existing proportional integral derivative (PID) and sliding mode controller (SMC) in terms of tracking accuracy and disturbance rejection.

Dietary inflammatory index, and depression and mortality risk associations in U.S. adults, with a special focus on cancer survivors.

Introduction: A higher risk for depression and mortality is associated with the inflammatory potential of diet measured through the Dietary Inflammatory Index (DII). The roles of DII in the risk of depression and death in cancer survivors were unclear. We aimed to examine the association between energy-adjusted DII (E-DII) score and risk of depression, and mortality using data from the 2007-2018 National Health and Nutrition Examination Survey (NHANES), with a special focus on cancer survivors. Methods: The 24-h dietary recall interview was used as a basis to calculate the E-DII score and the Patient Health Questionnaire-9 (PHQ-9) was used to measure the depressive outcomes. Logistic regression analyses were performed to determine the association between quartiles of E-DII score and depression. Cox proportional hazard regression and competing risk analyses were used to estimate the risks of quartiles of E-DII score or depression on mortality. Results: A total of 27,447 participants were included; including 24,694 subjects without cancer and 2,753 cancer survivors. The E-DII score and depression were not distributed differently between the two groups. However, the E-DII scores were positively associated with within each group's depression (all P trend < 0.001) and participants with higher E-DII scores had a higher risk of depression (subjects without cancer: ORQ4 vs Q1: 2.17, 95% CI: 1.75-2.70; cancer survivors: ORQ4 vsQ1: 1.78, 95% CI: 1.09-2.92). The median follow-up time were 87 person-months, a total of 1,701 (4.8%) and 570 (15.2%) all-cause deaths in subjects without cancer and cancer survivors were identified by the end of 2019. The highest E-DII scores quartile was associated with the highest risk of all-cause (HRQ4 vsQ1: 1.90, 95% CI: 1.54-2.35) and cardiovascular disease (CVD) cause death (HRQ4 vsQ1: 2.50, 95% CI: 1.69-2.3.7) in the subjects without cancer. Moreover, participants with depressive symptoms had higher all-cause mortality (HR: 1.29, 95% CI: 1.04-1.59). No significant correlation was found for E-DII scores or depression with all-cause, cancer-cause or CVD-cause mortality in cancer survivors. Conclusion: Our findings demonstrate that E-DII score was positively associated with depression risk. A higher E-DII score or depressive symptom may increase the risks of all-cause and CVD-cause mortality only among general subjects.

Microsatellite instability and Epstein-Barr virus combined with PD-L1 could serve as a potential strategy for predicting the prognosis and efficacy of postoperative chemotherapy in gastric cancer.

BACKGROUND: Microsatellite instability (MSI) and Epstein-Barr virus (EBV)-positive molecular subtypes exhibit complex immune responses in gastric cancer (GC), and PD-L1 has emerged as a prognostic biomarker associated with the cancer immune microenvironment. This study aimed to determine the prognostic value of molecular subtypes and whether the addition of PD-L1 would accurately predict the prognosis and guide postoperative chemotherapy for GC patients. METHODS: We performed molecular subtyping of tissue microarray slides from 226 GC patients who were treated with radical gastrectomy. The MSI status and PD-L1 expression were evaluated through immunohistochemistry (IHC) and EBV status through situ hybridization. Multiplex polymerase chain reaction (PCR) was also performed on 50 cases to validate the accuracy of IHC in defining MSI status. Differences in overall survival (OS) were assessed using the Kaplan-Meier method, log-rank test and Cox proportional hazards regression model. RESULTS: Among the 226 GC patients, 52 (23.2%) patients were classified as the MSI subtype, 11 (4.9%) were EBV+ subtype, and 161 (71.9%) were MSS (Microsatellite stable) /EBV subtype according to TCGA analysis. Two patients were both positive for MSI and EBV infection. EBV+ cases showed higher PD-L1 positivity than MSI cases and MSS/EBV cases (81.8% vs. 50.0% vs. 35.4%, P = 0.003). Compared with the non-MSS/EBV (MSI or EBV+ cases) subgroup, GC patients with MSS/EBV were associated with the worst outcomes (HR = 1.610, 95% CI [1.0462.479], P = 0.031). MSS/EBV GCs alone could benefit from postoperative chemotherapy (HR = 0.452, 95% CI [0.2990.682], P<0.001), and PD-L1-positive expression could also predict a better prognosis (HR = 0.612, 95% CI [0.3890.962], P = 0.033) in this subgroup. Considering both chemotherapy efficacy and PD-L1 expression in the MSS/EBV subgroup, chemotherapy could improve the prognosis for PD-L1-negative MSS/EBV GCs (HR = 0.357, 95% CI [0.2170.587], P <0.001) but not PD-L1-positive MSS/EBV GCs. CONCLUSIONS: Molecular subtyping combined with PD-L1 expression could serve as a potential strategy to better predict prognosis and guide postoperative chemotherapy of GC patients.