Diagnostic value of isolated plasma biomarkers and its combination in neurodegenerative dementias: A multicenter cohort study.

BACKGROUND: Plasma amyloid-ß (Aß), phosphorylated tau-181 (p-tau181), neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) potentially aid in the diagnosis of neurodegenerative dementias. We aim to conduct a comprehensive comparison between different biomarkers and their combination, which is lacking, in a multicenter Chinese dementia cohort consisting of Alzheimer's disease (AD), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP). METHODS: We enrolled 92 demented patients [64 AD, 16 FTD, and 12 PSP with dementia] and 20 healthy controls (HC). Their plasma Αß, p-tau181, NfL, and GFAP were detected by highly sensitive-single molecule immunoassays. Αß pathology in patients was measured by cerebrospinal fluid or/and amyloid positron emission tomography. RESULTS: All plasma biomarkers tested were significantly altered in dementia patients compared with HC, especially Aß42/Aß40 and NfL showed significant performance in distinguishing AD from HC. A combination of plasma Aß42/Aß40, p-tau181, NfL, and GFAP could discriminate FTD or PSP well from HC and was able to distinguish AD and non-AD (FTD/PSP). CONCLUSIONS: Our results confirmed the diagnostic performance of individual plasma biomarkers Aß42/Aß40, p-tau181, NfL, and GFAP in Chinese dementia patients and noted that a combination of these biomarkers may be more accurate in identifying FTD/PSP patients and distinguishing AD from non-AD dementia.

Optimal timing of GnRH antagonist initiation in IVF-ET: a retrospective cohort study on advanced maternal age women.

Background: Several studies have compared the effects of fixed and flexible gonadotropin releasing hormone antagonist (GnRH-ant) protocols during in vitro fertilization and embryo transfer (IVF-ET). However, which GnRH-ant initiation strategy is better remains controversial. Moreover, no studies have assessed the optimal timing of GnRH-ant initiation in women of advanced maternal age (AMA). Methods: In this retrospective cohort study, a total of 472 infertile women aged ≥ 35 years old undergoing their first IVF cycle from August 2015 to September 2021 at a tertiary academic medical center were recruited, of whom 136 followed fixed GnRH-ant protocol and 336 followed flexible GnRH-ant protocol. The primary outcomes measured were the cumulative live birth rate (CLBR) per IVF cycle and the time to live birth (TTLB) from the date of oocyte retrieval. Cox proportional models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) of CLBR regarding GnRH-ant timing. Results: No significant difference in CLBR was found between the fixed and flexible GnRH-ant groups (27.9% vs 20.5%, p=0.105). The TTLB was also comparable between groups (10.56 vs 10.30 months, p=0.782). The Kaplan-Meier analysis for CLBR also showed comparable results between groups (P=0.351, HR=0.83; 95%CI: 0.56-1.23). After establishing a multiple Cox proportional hazard model, the fixed GnRH-ant group still had comparable CLBR with the flexible GnRH-ant group (HR=0.85; 95%CI: 0.53-1.38; P=0.518). Subgroup and sensitivity analyses also demonstrated similar results. Conclusion: GnRH-ant protocols can be tailored to the needs of AMA women, and timing of GnRH-ant initiation can be adjusted flexibly.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): contemporary advances and current controversies.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory syndrome with characteristic clinical, radiological, and pathological features, and can be effectively treated with corticosteroid-based immunotherapies. The exact pathogenesis of CLIPPERS remains unclear, and specific diagnostic biomarkers are not available. According to the 2017 diagnostic criteria, probable CLIPPERS should be considered in middle-aged patients with subacute onset of pontocerebellar symptoms and typical punctuate and curvilinear gadolinium enhancement lesions ("salt-and-pepper" appearance) located in the hindbrain (especially pons) on magnetic resonance imaging. In addition, CLIPPERS-mimics, such as central nervous system (CNS) lymphoma, and several antibody-associated autoimmune CNS diseases (e.g., myelin oligodendrocyte glycoprotein antibody-associated disease, autoimmune glial fibrillary acidic protein astrocytopathy, and anti-N-methyl-D-aspartate receptor encephalitis), should be extensively excluded. The prerequisite for definite CLIPPERS is the perivascular T-cell-predominant inflammatory infiltration observed on pathological analysis. A biopsy is strongly suggested when clinical/radiological red flags are present. Most patients with CLIPPERS respond well to corticosteroids and have a good prognosis. Long-term low-dose corticosteroid maintenance therapy or corticosteroids coupled with immunosuppressants are recommended to prevent the recurrence of the syndrome. The potential progression of CLIPPERS to lymphoma has been suggested in some cases; therefore, at least 2-year clinical and radiological follow-up is essential. Here, we critically review the recent developments and provided an update on the clinical characteristics, diagnostic criteria, differential diagnoses, and therapeutic management of CLIPPERS. We also discuss the current controversies in this context that can be resolved in future research studies.

Risk assessment, fitness cost, cross-resistance, and mechanism of tetraniliprole resistance in the rice stem borer, Chilo suppressalis.

The rice stem borer (RSB), Chilo suppressalis, a notorious rice pest in China, has evolved a high resistance level to commonly used insecticides. Tetraniliprole, a new anthranilic diamide insecticide, effectively controls multiple pests, including RSB. However, the potential resistance risk of RSB to tetraniliprole is still unknown. In this study, the tetraniliprole-selection (Tet-R) strain was obtained through 10 continuous generations of selection with tetraniliprole 30% lethal concentration (LC30 ). The realized heritability (h2 ) of the Tet-R strain was 0.387, indicating that resistance of RSB to tetraniliprole developed rapidly under the continuous selection of tetraniliprole. The Tet-R strain had a high fitness cost (relative fitness = 0.53). We established the susceptibility baseline of RSB to tetraniliprole (lethal concentration at LC50  = 0.727 mg/L) and investigated the resistance level of 6 field populations to tetraniliprole. All tested strains that had resistance to chlorantraniliprole exhibited moderate- to high-level resistance to tetraniliprole (resistance ratio = 27.7-806.8). Detection of ryanodine receptor (RyR) mutations showed that the Y4667C, Y4667D, I4758M, and Y4891F mutations were present in tested RSB field populations. RyR mutations were responsible for the cross-resistance between tetraniliprole and chlorantraniliprole. Further, the clustered regularly interspaced palindromic repeats (CRISPR) / CRISPR-associated protein 9-mediated genome-modified flies were used to study the contribution of RyR mutations to tetraniliprole resistance. The order of contribution of a single RyR mutation to tetraniliprole resistance was Y4667D > G4915E > Y4667C ≈ I4758M > Y4891F. In addition, the I4758M and Y4667C double mutations conferred higher tetraniliprole resistance than single Y4667C mutations. These results can guide resistance management practices for diamides in RSB and other arthropods.

Stroke-like onset of calcified brain metastases with Wallerian degeneration: a case report and review of the literature.

INTRODUCTION: Metastatic brain tumors are a common complication of systemic cancer. They tend to have a chronic onset and are located at the gray-white junction of the cerebral hemispheres, those larger than 9.4 mm in diameter are often accompanied by substantial vasogenic edema. Herein, we report a rare case of calcified metastatic adenocarcinoma with Wallerian degeneration. In addition, we discuss the atypical manifestations of brain metastases. CASE REPORT: A 71-year-old man who went through stroke-like onset twice during 8 months with a history of resection of the left pulmonary adenocarcinoma 5 years prior was examined. Diffusion weighted magnetic resonance imaging of the brain showed an enlarged open-ring-shaped hyperintensity on the left periventricular white matter and basal ganglia, with Wallerian degeneration on the left cerebral peduncle. Brain computed tomography revealed nodular calcification of the lesion. The pathology of stereotactic biopsy indicated metastatic adenocarcinoma. CONCLUSION: When patients present with acute nervous system symptoms and a previous history of cancer, the possibility of metastases should be considered, even if neuroimaging is atypical.

Effectiveness of oestrogen pretreatment in patients with expected poor ovarian response (POSEIDON groups 3 and 4) undergoing GnRH antagonist protocol: study protocol for a randomised controlled trial.

INTRODUCTION: Women characterised by diminished ovarian reserve are considered to have poor ovarian response (POR) according to Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria. Patients in this population often have a poor prognosis for treatment with assisted reproductive technology. In previous studies, oestrogen pretreatment before ovarian stimulation has been shown to have a beneficial effect. However, recent studies presented conflicting conclusions. This study aims to evaluate the effectiveness of oestrogen pretreatment in patients with expected POR (POSEIDON groups 3 and 4) undergoing gonadotrophin releasing hormone antagonist (GnRH-ant) protocol. METHODS AND ANALYSIS: A prospective superiority randomised parallel controlled trial will be conducted at a tertiary university-affiliated hospital. A total of 316 patients will be randomly divided into two groups at a ratio of 1:1. In the intervention group, oral oestrogen pretreatment will be administered from day 7 after ovulation until day 2 of the next menstrual cycle. Afterwards, a flexible GnRH-ant protocol will be initiated. The control group will receive no additional intervention beyond routine ovarian stimulation. The primary outcome is the number of oocytes retrieved. Secondary outcomes include the total number of retrieved metaphase II oocytes, average daily dose of gonadotropin, total gonadotropin dose and duration of ovarian stimulation, cycle cancellation rate, top quality embryos rate, blastocyst formation rate, embryo implantation rate, clinical pregnancy rate, early miscarriage rate and endometrial thickness on trigger day. All data will be analysed according to the intention-to-treat and per-protocol principles. ETHICS AND DISSEMINATION: The ethical approval has been confirmed by the reproductive ethics committee of the affiliated hospital of Shandong University of Traditional Chinese Medicine (SDUTCM/2022.9.20). In addition, written informed consent will be obtained from all the participants before the study. The results will be disseminated via publications. TRIAL REGISTRATION NUMBER: ChiCTR2200064812.

The role of Erzhi Tiangui formula in expected poor ovarian responders undergoing in vitro fertilization-embryo transfer: A multicenter, randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Advanced age is one of the primary risk factors for infertility. Poor ovarian response (POR) to exogenous gonadotropin is a prominent characteristic of advanced-age women undergoing in vitro fertilization and embryo transfer (IVF-ET), which results in fewer retrieved oocytes and poor pregnancy outcomes. Traditional Chinese medicine (TCM) has been shown to improve female fertility. Erzhi Tiangui (EZTG) formula, in the form of granules with 10 herbal ingredients, demonstrated potential benefits in improving oocyte and embryo quality and ovarian reserve. Thus, this study aims to evaluate the efficacy and safety of EZTG formula. METHOD: The study is a multicenter, double-blind, placebo-controlled, randomized controlled trial (RCT), which will be conducted at 10 reproductive centers of tertiary hospitals. This study will enroll 480 women with expected POR of advanced age (≥35 years old) who fulfill the 2011 Bologna criteria. Participants will be assigned to either the EZTG group or the placebo group at random in an equal ratio. Each individual will receive conventional IVF-ET with EZTG granules or placebo as a complementary treatment. The primary outcome is the number of oocytes retrieved. Adverse events and safety assessments will be also conducted. DISCUSSION: This study aims to provide robust evidence of the efficacy and safety of EZTG formula as a complementary treatment for advanced-age women with expected POR undergoing IVF-ET.

Strategy for oxygen vacancy enriched CoMn spinel oxide catalyst activated peroxodisulfate for tetracycline degradation: process, mechanism, and toxicity analysis.

Antibiotic-like organic pollutants are harmful to aquatic ecosystems and seriously disrupt the ecological balance. Herein, we propose a simple and versatile method to prepare cobalt-manganese oxides with high specific surface area and abundant oxygen vacancies using low-temperature reduction crystallization, which greatly facilitates the adsorption and electron transfer between the catalyst, PDS, and TC, thus accelerating the degradation of tetracycline (TC). Among them, the degradation efficiency of TC in the CoMn2O4(C)/PDS system was 99.8% in 60 min and the degradation rate remained above 90% after four cycles. The possible degradation mechanism is also discussed, where Co is the main metal active center of the catalyst and Mn plays an auxiliary catalytic role to promote the generation of reactive radicals in PDS through redox interactions between Co and Mn, where SO4 -˙ is the main active species for TC degradation. Finally, the possible degradation pathways of TC are proposed and the toxicity of the intermediates is evaluated. Findings from this work will shed light on the rational design of bimetallic oxide catalysts.

Prevalence and factors of discordance attitudes toward advance care planning between older patients and their family members in the primary medical and healthcare institution.

Background: This study aimed at investigating the prevalence and factors of the discordant attitudes toward advance care planning (ACP) among older patients and their family members toward patients' engagement in ACP in the primary medical and healthcare institution. Methods: In a cross-sectional study, a total of 117 older patients and 117 family members from Jinhua Fifth Hospital in China were enrolled. The questionnaire included sociodemographic characteristics, functional capacity assessment, and attitudes toward patients' engagement in ACP. Functional capacity assessment scales included the Modified Barthel Index (MBI), the Short-Form Mini-Nutritional Assessment (MNA-SF), the 15-item Geriatric Depression Scale (GDS-15), the Mini-Mental State Examination (MMSE), the Clinical Frailty Scale (CFS), and the SARC-F questionnaire. Results: The discordance attitudes toward patients' engagement in ACP between patients and family members accounted for 41(35.0%). In the multivariate logistic analysis, factors associated with higher odds of discordance attitudes toward patients' engagement in ACP included greater age differences between patients and family members (OR = 1.043, 95% CI: 1.007-1.081), lower educational level for family members (OR = 3.373, 95% CI: 1.239-9.181), the patient's higher GDS-15 score (OR = 1.437, 95% CI: 1.185-1.742), and patient's higher MNA-SF score (OR = 1.754, 95% CI: 1.316-2.338). Conclusion: Older patients and their family members had little ACP knowledge, and factors that influence discordance attitudes toward patients' engagement in ACP included the age gaps between patients and family members, family members' educational level, patients' depressive symptoms, and patients' nutritional status.

Anastomotic Rings and Inflammation Values as Biomarkers for Leakage of Stapled Circular Colorectal Anastomoses.

Reliable markers to predict or diagnose anastomotic leakage (AL) of stapled circular anastomoses following colorectal resections are an important clinical need. Here, we aim to quantitatively investigate the morphology of anastomotic rings as an early available prognostic marker for AL and compare them to established inflammatory markers. We perform a prospective single-center cohort study, including patients undergoing stapled circular anastomosis between August 2020 and August 2021. The predictive value of the anastomotic ring configuration and the neutrophil-to-lymphocyte ratio (NLR) regarding anastomotic leakage is examined by ROC analyses and compared to the C-reactive protein (CRP) as an established marker. We included 204 patients, of which 19 suffered from anastomotic leakage (LEAK group), while in 185 patients the anastomoses healed well (HEAL group). The minimal height of the anastomotic rings as a binary classifier had a good ROC-AUC of 0.81 but was inferior to the NLR at postoperative day (POD) 5, with an excellent ROC-AUC of 0.93. Still, it was superior to the NLR at POD 3 (0.74) and the CRP at POD 3 (ROC-AUC 0.54) and 5 (ROC-AUC 0.70). The minimal height of the anastomotic rings as indicator for technically insufficient anastomoses is a good predictor of AL, while postoperatively the NLR was superior to the CRP in prediction of AL.

Detecting vulnerable carotid plaque and its component characteristics: Progress in related imaging techniques.

Carotid atherosclerotic plaque rupture and thrombosis are independent risk factors for acute ischemic cerebrovascular disease. Timely identification of vulnerable plaque can help prevent stroke and provide evidence for clinical treatment. Advanced invasive and non-invasive imaging modalities such as computed tomography, magnetic resonance imaging, intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy can be employed to image and classify carotid atherosclerotic plaques to provide clinically relevant predictors used for patient risk stratification. This study compares existing clinical imaging methods, and the advantages and limitations of different imaging techniques for identifying vulnerable carotid plaque are reviewed to effectively prevent and treat cerebrovascular diseases.

Occurrence of Intracranial Hemorrhage and Associated Risk Factors in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) is thought to be a rare but probably underestimated presentation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We conducted a systematic review and meta-analysis with the aim of comprehensively revealing the occurrence of ICH in patients with CADASIL. METHODS: English-language studies published up to September 30, 2021 were searched for in the MEDLINE (PubMed), Web of Science, and Cochrane Library databases. The design, patient characteristics, occurrence rate of ICH, and associated risk factors were retrieved for each identified relevant study. RESULTS: We enrolled 13 studies in the final meta-analysis, which included 1,310 patients with CADASIL. The probability of ICH occurrence in patients with CADASIL was 10.1% (95% confidence interval [CI]=5.6%-18.0%, I²=85.1%). When stratified by geographic region, the occurrence rate of ICH was much higher in Asians (17.7%; 95% CI=11.0%-28.5%, I²=76.3%) than in Europeans (2.0%; 95% CI=0.4%-10.8%, I²=82.8%). A higher burden of cerebral microbleeds (CMBs) and a history of hypertension were the most commonly recorded risk factors for ICH, which were available for three and two of the included studies, respectively. CONCLUSIONS: Our study suggests that ICH is an important clinical manifestation of CADASIL, especially in Asians. A higher burden of CMBs and the existence of hypertension were found to be associated with a higher probability of ICH occurrence in patients with CADASIL.

Develop a diagnostic tool for dementia using machine learning and non-imaging features.

Background: Early identification of Alzheimer's disease or mild cognitive impairment can help guide direct prevention and supportive treatments, improve outcomes, and reduce medical costs. Existing advanced diagnostic tools are mostly based on neuroimaging and suffer from certain problems in cost, reliability, repeatability, accessibility, ease of use, and clinical integration. To address these problems, we developed, evaluated, and implemented an early diagnostic tool using machine learning and non-imaging factors. Methods and results: A total of 654 participants aged 65 or older from the Nursing Home in Hangzhou, China were identified. Information collected from these patients includes dementia status and 70 demographic, cognitive, socioeconomic, and clinical features. Logistic regression, support vector machine (SVM), neural network, random forest, extreme gradient boosting (XGBoost), least absolute shrinkage and selection operator (LASSO), and best subset models were trained, tuned, and internally validated using a novel double cross validation algorithm and multiple evaluation metrics. The trained models were also compared and externally validated using a separate dataset with 1,100 participants from four communities in Zhejiang Province, China. The model with the best performance was then identified and implemented online with a friendly user interface. For the nursing dataset, the top three models are the neural network (AUROC = 0.9435), XGBoost (AUROC = 0.9398), and SVM with the polynomial kernel (AUROC = 0.9213). With the community dataset, the best three models are the random forest (AUROC = 0.9259), SVM with linear kernel (AUROC = 0.9282), and SVM with polynomial kernel (AUROC = 0.9213). The F1 scores and area under the precision-recall curve showed that the SVMs, neural network, and random forest were robust on the unbalanced community dataset. Overall the SVM with the polynomial kernel was found to be the best model. The LASSO and best subset models identified 17 features most relevant to dementia prediction, mostly from cognitive test results and socioeconomic characteristics. Conclusion: Our non-imaging-based diagnostic tool can effectively predict dementia outcomes. The tool can be conveniently incorporated into clinical practice. Its online implementation allows zero barriers to its use, which enhances the disease's diagnosis, improves the quality of care, and reduces costs.

The Role of Exosomes as Mediators of Neuroinflammation in the Pathogenesis and Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a common neurodegenerative disease characterized by progressive dementia. Accumulation of ß-amyloid peptide 1-42 and phosphorylation of tau protein in the brain are the two main pathological features of AD. However, comprehensive studies have shown that neuroinflammation also plays a crucial role in the pathogenesis of AD. Neuroinflammation is associated with neuronal death and abnormal protein aggregation and promotes the pathological process of ß-amyloid peptide 1-42 and tau protein. The inflammatory components associated with AD include glial cells, complement system, cytokines and chemokines. In recent years, some researchers have focused on exosomes, a type of membrane nano vesicles. Exosomes can transport proteins, lipids, microRNAs and other signaling molecules to participate in a variety of signaling pathways for signal transmission or immune response, affecting the activity of target cells and participating in important pathophysiological processes. Therefore, exosomes play an essential role in intercellular communication and may mediate neuroinflammation to promote the development of AD. This paper reviews the occurrence and development of neuroinflammation and exosomes in AD, providing a deeper understanding of the pathogenesis of AD. Furthermore, the role of exosomes in the pathogenesis and treatment of AD is further described, demonstrating their potential as therapeutic targets for neuroinflammation and AD in the future.

New cerebral microbleeds in AF patients on non-vitamin K oral anticoagulants or warfarin: One-year follow-up.

ABSTRACT: Anticoagulant treatment increases the risk of intracerebral hemorrhage (ICH), but whether the treatment, more specifically non-vitamin K oral anticoagulants (NOACs), increases the risk of cerebral microbleeds (CMBs) remains uncertain. We performed this study to investigate the development of new CMBs due to NOACs or warfarin treatment in patients with atrial fibrillation (AF).We prospectively recruited AF patients before anticoagulation from June 2016 to June 2018. We performed susceptibility-weighted imaging (SWI) examinations on all enrolled AF patients and re-examined SWI 1 year later. We compared demographic features and new CMBs between the NOACs group and the warfarin group. Univariate analysis of clinical factors was performed according to the development of new CMBs; and age, a HAS-B(L)ED score, warfarin use, and the presence of baseline CMBs were then selected for inclusion in the multivariate logistic regression model.A total of 72 AF patients were recruited, 29 of whom were assigned to the NOACs group and 43 to the warfarin group. Finally, 1 patient in the NOACs group (3.4%) and 9 patients (20.9%) in the warfarin group developed new CMBs after 1 year follow-up (P = .08). Univariate analysis showed that age, a HAS-B(L)ED score ≥4, the presence of baseline CMBs were associated with the development of new CMBs (P < .05). And multivariate regression analysis showed baseline CMBs (P = .03, odds ratio = 6.37, 95% confidence interval 1.15-35.36) was independently related to the increase in new CMBs.AF patients treated with NOACs may have a decreased trend in the development of new CMBs compared with those treated with warfarin. Baseline CMBs increased the frequency of new CMBs during anticoagulant treatment. The development of new CMBs in AF patients with anticoagulation requires further longitudinal studies with longer follow-up in larger samples.

T-Cell Non-Hodgkin Lymphoma of the Ileum Presenting as Perforation and Peritonitis: A Case Report.

Background: Non-Hodgkin lymphoma (NHL) of the ileum, presenting as perforation and peritonitis, is a rare disease, derived from intestinal intraepithelial T lymphocytes. The degree of malignancy is extremely high. The pathogenesis of ileal perforation caused by NHL remains unclear, as well as the chromosome and immune system abnormalities, which may be related to NHL, and are indistinguishable from other benign and malignant conditions and are clinically nonspecific. Case Report: We describe an 84-year-old man with abdominal pain for 4 days, which was aggravated for 3 h. The pain was in the upper abdominal region and was initially considered to be due to gastrointestinal perforation. He had persistent insidious pain, accompanied by nausea, vomiting, and fever. Physical examination indicated that the patient had pain all over the abdomen; also, rebound pain and muscle tension, and bowel sounds were reduced on auscultation. An abdominal CT scan showed free gas in the abdominal cavity. The patient was diagnosed with peritonitis due to hollow viscus perforation. A prompt exploratory laparotomy was performed. Intraoperative findings showed perforations in the ileum that are approximately 40 cm from the ileocecal region, which were 3-8 mm in size. A segmental distribution was observed, and the intestinal contents overflowed with purulent discharge around the perforation surface. Resection and ileostomy were performed, and the clinical histopathological examination confirmed T-cell lymphoma. The patient was advised to visit the Oncology Department for further chemotherapy. Conclusion: Timely emergency surgery is the key to the treatment of ileal perforation caused by T-cell lymphoma. Resection and ileostomy were performed as intervention measures, and subsequent histopathological examination manifested T-cell lymphoma.

Research Progress on the Relationship Between Inflammation and Colorectal Cancer.

Colorectal cancer is one of the common malignant tumors. Relevant epidemiology and a large number of experimental studies have proved that chronic inflammation is highly correlated with the occurrence and development of colorectal cancer. And inflammatory bowel disease has been proven to be an independent risk factor for colorectal cancer. Various inflammatory cells participate in the establishment of the chronic inflammatory intestinal microenvironment required for the onset of colorectal cancer. The abnormal signal pathways mediated by various inflammatory factors and inflammatory mediators promote the occurrence of tumors, which are related to colorectal cancer and pathogenesis-related inflammation mechanisms. At the gene level, miRNAs can also affect the pathogenesis of colorectal cancer by regulating mesenchymal epithelial transformation. This article reviews the relationship between inflammation and colorectal cancer as well as the related inflammatory mechanisms.

Evaluation of the Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes in China.

Background: Recently, the paraneoplastic neurologic syndrome (PNS) diagnostic criteria have received a major update with a new score system over the past 16 years. We aimed to evaluate the diagnostic performance and clinical utility in China. Methods: An eligible cohort of 113 Chinese patients diagnosed with PNSs from the Second Affiliated Hospital School of Medicine Zhejiang University and published data were enrolled retrospectively. Data including clinical phenotype, antibody type, the presence of cancer, and duration of follow-up were reviewed and re-evaluated to classify the diagnostic levels for the 2004 and 2021 PNS criteria. The performances of these 2 criteria were compared. The critical parameters of antibody and cancer for the updated criteria were further explored. Results: The cohort consisted of 69 males and 44 females with a median age of 60 years. Limbic encephalitis (23, 20.4%), anti-Hu antibody (32, 28.3%), and small-cell lung cancer (32, 28.3%) were the most common clinical phenotype, detected antibody, and concomitant cancer, respectively. A total of 97 (85.8%) patients were diagnosed with definite PNS according to the 2004 criteria: only 42.3% (41/97) fulfilled the 2021 criteria, while the remaining 40, 14, and 2 re-diagnosed with probable PNS, possible PNS, and non-PNS. The requirement of cancers consistent with antibody and phenotype increased the specificity and thus greatly enhanced the accuracy of the 2021 criteria. Conclusion: The updated criteria for PNS emphasized the consistency between cancer phenotype and antibody and showed a better diagnostic value. A better diagnostic yield could benefit disease management.

Association between plasminogen activator inhibitor-1 gene polymorphisms and susceptibility to Parkinson's disease in Chinese patients.

PURPOSE: Parkinson's disease (PD) is a neurodegenerative disease that usually leads to memory impairment, cognitive decline and dementia. Previous studies have reported that plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms play important roles in cardiovascular diseases, obesity, inflammation and other diseases. However, the role of PAI-1 in the diagnosis of Parkinson's disease has not been reported so far. METHODS: This study was a case-control study. This study included 131 PD patients and 97 healthy volunteers. polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze the polymorphic loci of five different regions in PAI-1 gene (rs2227631, rs1799889, rs6092, rs2227694 and rs7242). 60 PD patients and 60 healthy volunteers were selected to detect the plasma PAI-1 concentration. The allele and genotype frequencies of SNPs were assessed using the SHEsis program. RESULTS: We found that GG genotype frequency and G allele frequency of rs2227631 was significantly higher in the PD patients. Statistically significant difference for rs1799889 could be observed in overdominant model. In subgroup analysis, a significant difference in genotype frequency distribution and allele frequency was found for rs2227631 and rs1799889 between early-onset PD group and the control group. For cognitive dysfunction, the subcomponent showed that GG genotype frequency and G allele frequency of rs2227631 was significantly higher in normal cognition group. The codominant model of rs1799889 was significantly different between the cognitive impairment group and the control group. In addition, the expression of PAI-1 in plasma of PD patients was significantly higher than that of controls, and further analysis showed that the expression of PAI-1 in patients with cognitive impairment was significantly higher than that in patients with cognitive normal. CONCLUSION: Our results indicate that the PAI-1 gene rs2227631 and rs1799889 polymorphisms were significantly associated with PD susceptibility in the Chinese Han population. PAI-1 has the potential to become a new therapeutic target and diagnostic marker.

Analysis of Alterations of the Gut Microbiota in Moderate to Severe Psoriasis Patients Using 16S rRNA Gene Sequencing.

Background: Psoriasis is an inflammatory skin disease. The correlation between intestinal microbiota and immune-mediated diseases makes scientists pay attention to the pathogenic role of microbiota. Objective: The aim of this study was to identify the gut microbial composition of patients with psoriasis. Methods: 16S rRNA gene sequencing method was used to analyse the faecal samples which was collected from 28 moderately severe psoriasis patients and 21 healthy controls and was followed by the analysing of informatics methods. Results: No visible differences can be observed in the diversity of gut microbiota between the psoriasis and the healthy patients, but the composition of the gut microbiota illustrate significant distinction between these two groups. At the phylum level, compared to the healthy control group, the psoriasis group shows higher relative abundance of Bacteroidetes and lower relative abundance of Proteobacteria (P < 0.05). At the genus level, unidentified_Enterobacteriaceae, unidentified_Lachnospiraceae, Romboutsia, Subdoligranulum, unidentified_Erysipelotrichaceae, Dorea were relatively less abundant in psoriasis patients, whereas Lactobacillus, Dialister were relatively more abundant in psoriasis group (all P < 0.05). LefSe analysis (linear discriminant analysis effect size) indicated that Negativicutes and Bacteroidia were potential biomarkers for psoriasis. Conclusion: This study identified the intestinal microecological environment of patients with psoriasis and healthy people, proving that psoriasis patients have a remarkably disturbed microbiome, and found several biomarkers of intestinal microorganisms in patients with psoriasis.