Characterization of GABAergic marker expression in prefrontal cortex in dexamethasone induced depression/anxiety model.

Background: The pivotal responsibility of GABAergic interneurons is inhibitory neurotransmission; in this way, their significance lies in regulating the maintenance of excitation/inhibition (E/I) balance in cortical circuits. An abundance of glucocorticoids (GCs) exposure results in a disorder of GABAergic interneurons in the prefrontal cortex (PFC); the relationship between this status and an enhanced vulnerability to neuropsychiatric ailments, like depression and anxiety, has been identified, but this connection is still poorly understood because systematic and comprehensive research is lacking. Here, we aim to investigate the impact of dexamethasone (DEX, a GC receptor agonist) on GABAergic interneurons in the PFC of eight-week-old adult male mice. Methods: A double-blind study was conducted where thirty-two mice were treated subcutaneously either saline or DEX (0.2 mg/10 ml per kg of body weight) dissolved in saline daily for 21 days. Weight measurements were taken at five-day intervals to assess the emotional changes in mice as well as the response to DEX treatment. Following the 21-day regimen of DEX injections, mice underwent examinations for depression/anxiety-like behaviours and GABAergic marker expression in PFC. Results: In a depression/anxiety model generated by chronic DEX treatment, we found that our DEX procedure did trigger depression/anxiety-like behaviors in mice. Furthermore, DEX treatment reduced the expression levels of a GABA-synthesizing enzyme (GAD67), Reelin, calcium-binding proteins (parvalbumin and calretinin) and neuropeptides co-expressed in GABAergic neurons (somatostatin, neuropeptide Y and vasoactive intestinal peptide) in the PFC were reduced after 21 days of DEX treatment; these reductions were accompanied by decreases in brain size and cerebral cortex thickness. Conclusion: Our results indicate that a reduction in the number of GABAergic interneurons may result in deficiencies in cortical inhibitory neurotransmission, potentially causing an E/I imbalance in the PFC; this insight suggests a potential breakthrough strategy for the treatment of depression and anxiety.

Pneumocystis pneumonia in stage IIIA lung adenocarcinoma with immune-related acute kidney injury and thoracic radiotherapy: A case report.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are therapeutic agents for advanced and metastatic non-small cell lung cancer (NSCLC) with high clinical antitumor efficacy. However, immune-related adverse events occur in 20% of these patients and often requiring treatment with immunosuppressive agents, such as corticosteroids. Consequently, this may increase the risk of patients to opportunistic infections. Pneumocystis jirovecii pneumonia (PJP), a rare but serious opportunistic infection typically observed in patients with human immunodeficiency virus, can also occur in cancer patients undergoing long-term glucocorticoid treatment. CASE SUMMARY: We report a case of a 56-year-old male with squamous NSCLC treated with triplimab combined with paclitaxel, carboplatin, and radical thoracic radiation therapy. Following this regimen, he developed acute kidney injury (AKI) with elevated creatinine levels. After concurrent radical chemoradiotherapy ended, he developed a grade 3 immune-related AKI. High-dose corticosteroids were administered to treat AKI, and renal function gradually recovered. Corticosteroids were reduced to a dose of 10 mg prednisone equivalent daily eight weeks later; however, he developed severe pneumonia with spontaneous pneumothorax. Next-generation sequencing of the bronchoscopic lavage revealed PJP co-infection with herpes simplex virus 1 and cytomegalovirus. The inflammation was more severe in areas exposed to radiation. Piperacillin-tazobactam, acyclovir, sulfamethoxazole, and trimethoprim were used to control the infection. The patient recovered, and immunotherapy was terminated. CONCLUSION: PJP is rare but can occur in patients with ICI adverse events and should be differentiated from tumor progression or immune-related adverse events. Thoracic radiation may increase risk, necessitating careful monitoring and prevention.

Modification of the association between coffee consumption and constipation by alcohol drinking: A cross-sectional analysis of NHANES 2007-2010.

BACKGROUND: The association between coffee consumption and constipation remains unclear. This study aimed to examine the relationship of coffee consumption with the risk of constipation, while also investigating potential effect modifiers. METHODS: This cross-sectional study included 7844 participants from the National Health and Nutrition Examination Survey (NHANES) 2007-2010. Coffee consumption was extracted from the 24-hour dietary recall. Constipation was assessed using the Bristol Stool Form Scale. The association between coffee consumption and constipation was assessed using multivariable restricted cubic spline and logistic regression with odds ratio (OR) and 95% confidence interval (CI). RESULTS: There was a J-shaped relationship between total coffee consumption and the risk of constipation in the whole population (p for nonlinearity = 0.049), with 1-2 cups/day of total coffee potentially reducing the risk of constipation by 39% (OR 0.61, 95% CI 0.35-1.06, p = 0.07). As for caffeinated coffee, a J-shaped association between its consumption and the risk of constipation was also observed in the whole population (p for nonlinearity = 0.008), with 1-2 cups/day being significantly associated with a reduced risk (OR 0.57, 95% CI 0.35-0.95, p = 0.03). When restricting to never drinkers of alcohol, the associations between total and caffeinated coffee consumption and constipation shifted to inverse linear trends, where at least 3 cups/day was significantly associated with an 88% reduction in constipation risk (total coffee: OR 0.12, 95% CI 0.02-0.68, p = 0.02; caffeinated coffee: OR 0.12, 95% CI 0.02-0.70, p = 0.02). Decaffeinated coffee showed no association with constipation. CONCLUSIONS: Consuming 1-2 cups of caffeinated coffee daily was associated with a reduced risk of constipation in the general population. Among never drinkers of alcohol, a linear protective effect was observed, with a notable 88% reduction in constipation risk for those consuming at least 3 cups per day. Moderate caffeinated coffee intake may therefore be a viable dietary strategy for managing constipation in the general population.

Perioperative systemic and prophylactic intraperitoneal chemotherapy for type 4/large type 3 gastric cancer: DRAGON-10.

Large type 3 and type 4 gastric cancers (GC) have a significantly poor prognosis, primarily due to their high predisposition for peritoneal dissemination. The application of intraperitoneal chemotherapy has emerged as a viable therapeutic strategy for managing GC patients with peritoneal metastasis. This study is planned to enroll 37 resectable large type 3 or type 4 GC patients. These patients are scheduled to undergo a treatment comprising preoperative chemotherapy with paclitaxel, oxaliplatin and S-1, followed by D2 gastrectomy, and concluding with postoperative treatments that include prophylactic intraperitoneal chemotherapy. The study's primary objective is to evaluate the 3-year peritoneal recurrence rate. Secondary objectives are to assess the 3-year disease-free survival, 3-year overall survival and to monitor the adverse events.Clinical trial registration number: ChiCTR2400083253 (https://www.chictr.org.cn).

Gastric cancer (GC), specifically the large type 3 and type 4 kinds, is a serious health condition that often leads to a very poor chance of survival. This is mainly because these types of cancer easily spread to the lining of the abdomen, a process known as peritoneal dissemination. One way to tackle this issue is through a treatment known as intraperitoneal chemotherapy, which directly targets the abdominal lining to kill cancer cells. In our study, 37 resectable large type 3 and type 4 GC patients will receive a combination of chemotherapy drugs before undergoing surgery to remove the cancer. After surgery, they will receive additional treatment that combines chemotherapy into the abdomen with standard chemotherapy. The main goal of our study is to see if this treatment approach can reduce the chance of cancer returning to the abdominal lining within 3 years. We are also looking at how long patients remain free from cancer, their overall survival after 3 years, and any side effects they may experience from the treatment. This study aims to provide a clearer understanding of how effective this combined treatment is for patients with these aggressive types of GC, with the hope of improving their chances of survival and quality of life.

Nanopore-based full-length transcriptome sequencing for understanding the underlying molecular mechanisms of rapid and slow progression of diabetes nephropathy.

BACKGROUND: Diabetic nephropathy (DN) has been a major factor in the outbreak of end-stage renal disease for decades. As the underlying mechanisms of DN development remains unclear, there is no ideal methods for the diagnosis and therapy. OBJECTIVE: We aimed to explore the key genes and pathways that affect the rate progression of DN. METHODS: Nanopore-based full-length transcriptome sequencing was performed with serum samples from DN patients with slow progression (DNSP, n = 5) and rapid progression (DNRP, n = 6). RESULTS: Here, transcriptome proclaimed 22,682 novel transcripts and obtained 45,808 simple sequence repeats, 1,815 transcription factors, 5,993 complete open reading frames, and 1,050 novel lncRNA from the novel transcripts. Moreover, a total of 341 differentially expressed transcripts (DETs) and 456 differentially expressed genes (DEGs) between the DNSP and DNRP groups were identified. Functional analyses showed that DETs mainly involved in ferroptosis-related pathways such as oxidative phosphorylation, iron ion binding, and mitophagy. Moreover, Functional analyses revealed that DEGs mainly involved in oxidative phosphorylation, lipid metabolism, ferroptosis, autophagy/mitophagy, apoptosis/necroptosis pathway. CONCLUSION: Collectively, our study provided a full-length transcriptome data source for the future DN research, and facilitate a deeper understanding of the molecular mechanisms underlying the differences in fast and slow progression of DN.

Delirium and Weakness Acquired in the Intensive Care Unit: Individual and Combined Effects on 90-Day Mortality in Survivors of Critical Illness.

AIMS: To compare the individual and combined effects on 90-day mortality among four critically ill survivor groups: normal (without ICU-acquired delirium or ICU-acquired weakness), delirium-only (with ICU-acquired delirium only), weakness-only (with ICU-acquired weakness only) and delirium-weakness (combined ICU-acquired delirium and weakness). METHODS: A prospective cohort study consecutively recruited delirium-free critically ill patients admitted to six medical ICUs at a university hospital. Delirium was assessed once daily for 14 days (or until death or ICU discharge) using the Confusion Assessment Method for the ICU. Participants who were discharged from the ICUs were assessed for weakness using the Medical Research Council scale. A summed score below 48 defines ICU-acquired weakness. These survivors were evaluated again for 90-day mortality. The study is reported using the STROBE checklist. RESULTS: Delirium developed in 107 (43.2%) participants during their first 14 days of ICU stay; 55 (22.2%) met criteria for weakness by ICU discharge. Participants with delirium were at increased risk for also developing ICU-acquired weakness, and the 90-day mortality was 18.2%. Independent of age and Acute Physiology and Chronic Health Evaluation II score at ICU admission, delirium-only and weakness-only were not associated with higher 90-day mortality, while participants in the delirium-weakness group had a 3.69-fold higher risk of death, compared to those who were normal during the ICU stay. A non-significant interaction was found, suggesting the joint effect of delirium and weakness on mortality is not higher than the sum of both effects individually. CONCLUSIONS: Mortality is substantially high among critically ill survivors who experience both delirium and weakness, although no additive effect on mortality was observed when these conditions occur together. Our findings highlight the urgent need to optimise ICU care by prioritising the prevention, early identification and management of these two common ICU-acquired conditions. PATIENT CONTRIBUTION: Study participation and completion of all assessments. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04206306.

The associations between modifiable risk factors and constipation: a comprehensive mendelian randomization study.

OBJECTIVE: Early identification of modifiable risk factors is crucial for the prevention of constipation. This study systematically investigated the relationship between genetically predicted modifiable risk factors and constipation. METHODS: The inverse variance weighting (IVW) method was employed as the primary analytical approach. For similar exposure indicators, the multivariate Mendelian randomization (MVMR) method was used to adjust for potential biases in univariate MR analysis. The robustness of the results was further evaluated using the MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis. Bonferroni correction was applied to reduce the false positive rate in the results. RESULTS: The IVW analysis indicated a significant causal association between genetically predicted gastroesophageal reflux disease [OR (95% CI) = 1.192 (1.079-1.315), P = 0.0005], atorvastatin use [OR (95% CI) = 16.995 (3.327-86.816), P = 0.0007], and constipation. Additionally, there was a potential causal association between education level [OR (95% CI) = 0.859 (0.767-0.964), P = 0.009], major depressive disorder [OR (95% CI) = 1.206 (1.041-1.399), P = 0.013], hypothyroidism [OR (95% CI) = 2.299 (1.327-3.985), P = 0.003], and aspirin use [OR (95% CI) = 4.872 (1.174-20.221), P = 0.029] with constipation. No causal associations were found for the other included indicators. Sensitivity analysis demonstrated the absence of evidence for heterogeneity and pleiotropy in any positive results. CONCLUSION: This study identified several risk factors that could be targeted for the prevention of constipation, offering valuable insights for public health policies.

Targeted isolation of lignans from the roots of Anthriscus sylvestris (L.) Hoffm. by small molecule accurate recognition technology.

Five undescribed lignans (1-5), along with sixteen known lignans (6-21), were isolated from the roots of Anthriscus sylvestris using small molecule accurate recognition technology (SMART). The structures of the isolated compounds were determined by comprehensive spectroscopic analyses, and the absolute configurations of compounds 3-5 were elucidated by comparison of their calculated and experimental ECD spectra. Compounds 5, 14-15, 19, and 21 exhibited significantly inhibitory effects against hypoxia-stimulated abnormal proliferation of pulmonary arterial smooth muscle cells (PASMCs). Moreover, compounds 5, 14-15, 19, and 21 can significantly restore expression of expression of PASMCs proliferation-related protein, including α-SMA, PCNA, P27, and CyclinD3, which are closely related to cell proliferation.

Neural dynamics underlying the illusion of control during reward processing.

The illusion of control refers to a behavioral bias in which people believe they have greater control over completely stochastic events than they actually do, leading to an inflated estimate of reward probability than objective probability warrants. In this study, we examined how reward system is modulated by the illusion of control through the lens of neural dynamics. Participants in a behavioral task exhibited a classical illusion of control, assigning a higher value to the gambling wheels they picked themselves than to those given randomly. An event-related potential study of the same task revealed that this behavioral bias is associated with reduced reward anticipation, as indexed by the stimulus-preceding negativity, diminished positive prediction error signals, as reflected by the reward positivity, and enhanced motivational salience, as revealed by the P300. Our findings offer a mechanistic understanding of the illusion of control in terms of reward dynamics.

Evidence for the Contribution of the miR-206/BDNF Pathway in the Pathophysiology of Depression.

Depression is a complex disorder with substantial impacts on individual health and has major public health implications. Depression results from complex interactions between genetic and environmental factors. Epigenetic mechanisms, including DNA methylation, microRNAs (miRNAs), and histone modifications, can produce heritable phenotypic changes without a change in DNA sequence and recently were proven to mediate lasting increases in the risk of depression following exposure to adverse life events. Of these, miRNAs are gaining attention for their role in the pathogenesis of many stress-associated mental disorders, including depression. One such miRNA is microRNA-206 (miR-206), which is a critical candidate for increasing the susceptibility to stress. Although miR-206 is thought to be a typical muscle-specific miRNA, it is expressed throughout the brain, particularly in the hippocampus and prefrontal cortex. Until now, only a few studies have been conducted on rodents to understand the role of miR-206 in stress-related abnormalities in neurogenesis. However, the precise underlying molecular mechanism of miR-206-mediated depression-like behaviors remains largely unknown. Here, we reviewed recent advances in the field of biomedical and clinical research on the role of miR-206 in the pathogenesis of depression from studies using different tissues and various experimental designs and described how abnormalities in miR-206 expression in these tissues can affect neuronal functions. Moreover, we focused on studies investigating the brain-derived neurotrophic factor (BDNF) as a functional target of miR-206, where miR-206 has been implicated in the pathogenesis of depression by suppressing the expression of the BDNF. In summary, these studies confirm the existence of a tight correlation between the pathogenesis of depression and the miR-206/BDNF pathway.

Interactions between mild depressive symptoms and amyloid pathology on the trajectory of neurodegeneration, cognitive decline, and risk of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) was driven by the interplay between modifiable environmental factors and ß-amyloid (Aß) pathology. We aimed to investigate the interaction effects of mild depressive symptoms (MDS) with Aß on AD development. METHODS: Longitudinal data of 1746 non-demented adults (mean age = 73 years, female = 53 %, maximum = 10 years) were derived from the Alzheimer's Disease Neuroimaging Initiative cohort. MDS was separately defined by the baseline status, longitudinal latent class, and average intensity during follow-up. Amyloid-positive (A+) status was determined based on cerebrospinal fluid levels of ß-amyloid. Regression models were employed to analyze the interactive effects of MDS with A+ on cognitive decline, neurodegeneration, and AD incidence. RESULTS: Individuals with both A+ status and MDS at baseline experienced the fastest neurodegeneration (p < 0.01), cognitive decline (p < 0.05), and a higher risk of developing AD (HR = 5.23, p < 0.001). Furthermore, A+ participants with the trajectory of increasing depressive symptoms demonstrated more pronounced neurodegeneration (p < 0.001), cognitive decline (p < 0.01), and elevated risk of AD (HR = 10.45, p < 0.001). Finally, A+ status in combination with a higher average intensity of depressive symptoms was associated with faster brain atrophy (p < 0.01) and brain metabolism decline (p < 0.05), cognitive decline (p < 0.05), and higher AD risk (HR = 13.99, p < 0.001). CONCLUSION: These findings emphasized that the MDS-Aß interaction relationship should be considered in risk stratification, prediction, and early management of neurodegeneration and cognitive decline in the pre-dementia stage.

Nitrogen-Doped Carbon Dots: A New Powerful Fluorescent Dye with Substantial Effect on Bacterial Cell Labeling.

Carbon dots (CDs)-minute carbon nanoparticles with remarkable luminescent properties, photostability, and low toxicity-show potential for various applications. CDs synthesized using citric acid and urea are the least toxic to biological environments. Here, we aimed to explore the effect of CDs synthesized using citric acid and urea at 50, 33, and 25% (CDs 1/1, 1/2, and 1/3, respectively) weight ratios in a microwave on bacterial cell fluorescence sensing and labeling. The nanoscale properties of CDs were investigated via transmission electron microscopy and dynamic light scattering particle size analysis. X-ray powder diffraction confirmed the graphitic structures of CDs. X-ray photoelectron spectroscopy revealed that the nitrogen content increased gradually with increasing urea ratios, indicating functional group changes. Transient photoluminescence decay periods demonstrated superior fluorescence intensity of CDs 1/3 under blue, green, and red lights. The use of CDs was notably more efficient than traditional methods in staining bacterial cells. Fluorescence microscopy of 10 g-positive and 10 g-negative bacteria revealed enhanced staining of Gram-positive strains, with CDs 1/3 presenting the best results. The CDs exhibited excellent photostability, maintaining poststaining fluorescence for 100 min, surpassing the performance of conventional dyes. CDs could serve as potential fluorescent dyes for the rapid discrimination of Gram-positive and Gram-negative bacteria.

Comparative Analysis of the Feasibility of Myocardial Blood Flow Index Versus CT-FFR in the Diagnosis of Suspected Coronary Artery Disease.

Background: Using fluid dynamic modeling, noninvasive fractional flow reserve (FFR) derived from coronary computed tomography angiography (CCTA) data provides better anatomic and functional information than CCTA, with a high diagnostic and discriminatory value for diagnosing hemodynamically significant lesions. Myocardial blood flow index (MBFI) based on CCTA is a physiological parameter that reflects myocardial ischemia. Thus, exploring the relationship between computed tomography derived fractional flow reserve (CT-FFR) and MBFI could be clinically significant. This study aimed to investigate the relationship between CT-FFR and MBFI and to analyze the feasibility of MBFI differing from CT-FFR in diagnosing suspected coronary artery disease (CAD). Methods: Data from 61 patients (35 males, mean age: 59.2 ± 10.02 years) with suspected CAD were retrospectively analyzed, including the imaging data of CCTA, CT-FFR, and data of invasive coronary angiography performed within one week after hospitalization. CT-FFR and MBFI were calculated, and the correlation between MBFI or CT-FFR and invasive coronary angiography (ICA) was evaluated. Using ICA (value ≥ 0.70) as the gold standard and determining the optimal cutoff value via a diagnostic test, the diagnostic performance of MBFI or CT-FFR was evaluated. Results: MBFI and CT-FFR were negatively correlated with ICA (r = -0.3670 and -0.4922, p = 0.0036 and 0.0001, respectively). Using ICA (value of ≥ 0.70) the gold standard, the optimal cutoff value was 0.115 for MBFI, and the area under the curve (AUC) was 0.833 (95% confidence interval [CI]: 0.716-0.916, Z = 5.357, p < 0.0001); using ICA (value of ≥ 0.70) the gold standard, the optimal cutoff value was 0.80 for CT-FFR, and the area under the curve (AUC) was 0.759 (95% CI: 0.632-0.859, Z = 3.665, p = 0.0002). No significant difference was observed between the AUCs of CT-FFR and MBFI (Z = 0.786, p = 0.4316). Conclusions: MBFI based on CCTA can be used to evaluate myocardial ischemia similar to CT-FFR in suspected CAD; however, it should be noted that CT-FFR is a functional index based on the anatomical stenosis of the coronary artery, whereas MBFI is a physiological index reflecting myocardial mass remodeling.

Distribution and Determinants of Anterior Chamber Angle and Anterior Chamber Volume in Young Chinese Adults.

PURPOSE: Current study aimed to understand the distribution and determinants of anterior chamber angle (ACA) and anterior chamber volume (ACV) in Chinese young adults, which can help fill current data gaps and aid in early detection and intervention for high-risk population of primary angle closure glaucoma. METHODS: This cross-sectional study utilized data from 2014 participants who completed questionnaire and eye examination in September 2021. ACV and ACA were measured using a Pentacam tomographer. Spherical equivalent (SE) was evaluated by autorefractor without cycloplegia. Central corneal thickness (CCT) and biomechanically corrected intraocular pressure (bIOP) were evaluated using Corvis-ST. Axial length (AL), corneal radius (CR), anterior chamber depth (ACD), and white to white were assessed using the IOL Master. RESULTS: A total of 1635 students were included in the analysis. The mean ACV and AVA were 194.74 ± 32.30 µL and 38.81 ± 4.84°, respectively. Males have a larger ACV and wider ACA than females. ACV was positively correlated with ACA (r = 0.24, p < 0.001), and the correlation was stronger for non-myopic students than for myopic students. Multivariable linear regression model showed that AL (ß = 2.41), CR (ß = -4.12), CCT (ß = -0.11), ACD (ß = 97.93), and bIOP (ß = 0.40) were associated with ACV, and CCT (ß = -0.01), CR (ß = 0.38), and ACD (ß = 7.41) were associated with ACA (all p < 0.05). Random forest model indicated that ACD was the most critical predictor of both ACV and ACA. CONCLUSIONS: This study reported the distribution and determinants of ACA and ACV. Deeper ACD was associated with larger ACV and wider ACA.

Serum folate levels and risk of metabolic dysfunction-associated steatotic liver disease: results from a cross-sectional study and Mendelian randomization analysis.

Background: Evidence from observational studies on the association between folate and metabolic dysfunction-associated steatotic liver disease (MASLD) is conflicting. Aims: This study aimed to investigate the association between serum folate concentration and MASLD and further assess the causal relationship using Mendelian randomization (MR) analysis. Methods: To investigate the causal relationship between serum folate and MASLD, we conducted a cross-sectional study that selected 1,117 participants from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). The association between serum folate level and the risk of MASLD was evaluated under a multivariate logistic regression model. In addition, we conducted a two-sample MR study using genetic data from a large genome-wide association study (GWAS) to compare serum folate level (37,465 individuals) and MASLD (primary analysis: 8,434 cases/770,180 controls; Secondary analysis:1,483 cases/17,781 controls) were performed to infer causal relationships between them. Inverse variance weighted (IVW) was used as the primary method of MR Analysis. Results: The results from the NHANES database showed that Tertile 3 group (Tertile 3: ≥ 48.6 nmol/L) had a significantly lower risk (OR = 0.58, 95% CI: 0.38-0.88, p = 0.010) of MASLD than Tertile 1 group (Tertile 1: < 22.3 nmol/L) after complete adjustments. However, in the IVW of MR analysis, there was no causal relationship between serum folate level and MASLD risk in the primary analysis (OR = 0.75, 95% CI: 0.55-1.02, p = 0.065) and secondary analysis (OR = 0.83, 95% CI: 0.39-1.74, p = 0.618). Conclusion: In observational analyses, we observed an inverse association between higher serum folate concentrations and a reduced risk of MASLD. Our MR study generated similar results, but the association failed to reach the significance threshold of p < 0.05, suggesting that our MR study does not support a causal relationship between serum folate levels and MASLD risk. Additional research involving a larger number of cases would contribute to enhancing the confirmation of our preliminary findings.

Notch1 signaling pathway promotes growth and metastasis of gastric cancer via modulating CDH5.

OBJECTIVE: To explore the underlying molecular mechanism of Notch1/cadherin 5 (CDH5) pathway in modulating in cell malignant behaviors of gastric cancer (GC). METHODS: We performed bioinformatic analyses to screen the potential target genes of Notch1 from cadherins in GC. Western blot and RT-PCR were conducted to detect CDH5 expression in GC tissues and cells. We utilized chromatin immunoprecipitation (CHIP) assays to assess the interaction of Notch1 with CDH5 gene. The effects of Notch1/CDH5 axis on the proliferation, invasion, migration and vasculogenic mimicry in GC cells were evaluated by EdU, wound healing, transwell, and tubule formation assays. RESULTS: Significantly increased CDH5 expression was found in GC tissues compared with paracancerous tissues and associated to clinical stage and poor overall survival (OS) in patients with GC. Notch1 positively regulate the expression of CDH5 in GC cells. CHIP assays validated that CDH5 was a direct target of Notch1. In addition, Notch1 upregulation enhanced the proliferation, migration, invasion and vasculogenic mimicry capacity of GC cells, which could be attenuated by CDH5 silencing. CONCLUSIONS: These results indicated Notch1 upregulation enhanced GC malignant behaviors by triggering CDH5, suggesting that targeting Notch1/CDH5 axis could be a potential therapeutic strategy for GC progression.

A dynamic online nomogram for predicts delayed postoperative bleeding after colorectal polyp surgery.

This study aims to analyze the risk factors associated with delayed postoperative bleeding (DPPB) following colorectal polyp surgery, develop a dynamic nomogram and evaluate the model efficacy, provide a reference for clinicians to identify the patients at high risk of DPPB. Retrospective study was done on patients who underwent endoscopic colorectal polypectomy at the First Hospital of Lanzhou University from January 2020 to March 2023. Differences between the group with and without DPPB were compared, and independent risk factors for DPPB occurrence were identified through univariate analysis and combination LASSO and logistic regression. A dynamic nomogram was constructed based on multiple logistic regression to predict DPPB following colorectal polyp surgery. Model evaluation included receiver operating characteristic (ROC), Calibration curve, Decision curve analysis (DCA). DPPB occurred in 38 of the 1544 patients included. multivariate analysis showed that direct oral anticoagulants (DOACs), polyp location in the right hemi colon, polyp diameter, drink, and prophylactic hemoclips were the independent risk factors for DPPB and dynamic nomogram were established. Model validation indicated area under the ROC curve values of 0.936, 0.796, and 0.865 for the training set, validation set, and full set, respectively. The calibration curve demonstrated a strong alignment between the predictions of the column-line diagram model and actual observations. The decision curve analysis (DCA) displayed a significant net clinical benefit across the threshold probability range of 0-100%. The dynamic nomogram aids clinicians in identifying high-risk patients, enabling personalized diagnosis and treatment.

The use of acupuncture for addressing neurological and neuropsychiatric symptoms in patients with long COVID: a systematic review and meta-analysis.

Importance: Acupuncture has been used to treat neurological and neuropsychiatric symptoms in China and other parts of the world. These symptoms, such as fatigue, headache, cognitive impairment, anxiety, depression, and insomnia, are common in people experiencing long COVID. Objective: This study aims to explore the feasibility of acupuncture in the treatment of neurological and neuropsychiatric symptoms in long COVID patients. Data Sources: A systematic search was conducted in four English and four Chinese databases from inception to 23 June 2023. Literature selection and data extraction were conducted by two pairs of independent reviewers. Study Selection: Randomized controlled trials (RCTs) that explored the effect of acupuncture on fatigue, depression, anxiety, cognitive abnormalities, headache, and insomnia were included. Data Extraction and Synthesis: RCTs that explored the effect of acupuncture on fatigue, depression, anxiety, cognitive abnormalities, headache, and insomnia were included. A meta-analysis was performed using R software. Heterogeneity was measured using I2. Subgroup analyses were performed focusing on the duration of treatment and acupuncture modalities. The systematic review protocol was registered on PROSPERO (registration number: CRD42022354940). Main outcomes and measures: Widely adopted clinical outcome scales included the Fatigue Scale for assessing fatigue, the Hamilton Depression Rating Scale for evaluating depression, the Mini-Mental State Examination for assessing cognitive impairment, the Visual Analog Scale for headache severity, and the Pittsburgh Sleep Quality Index for measuring insomnia. Results: A total of 110 RCTs were included in the systematic review and meta-analysis. Overall, acupuncture was found to improve the scores of the Fatigue Scale (vs. medication: mean differences (MD): -2.27, P < 0.01; vs. sham acupuncture: MD: -3.36, P < 0.01), the Hamilton Depression Rating Scale (vs. medication: MD: -1.62, 95%, P < 0.01; vs. sham acupuncture: MD: -9.47, P < 0.01), the Mini-Mental State Examination (vs. medication: MD: 1.15, P < 0.01; vs. sham acupuncture: MD: 1.20, P < 0.01), the Visual Analog Scale (vs. medication: MD: -1.05, P < 0.01; vs. waitlist: MD: -0.48, P=0.04), and the Pittsburgh Sleep Quality Index (vs. medication: MD: -2.33, P < 0.01; vs. sham acupuncture: MD: -4.19, P < 0.01). Conclusion and relevance: This systematic review suggested acupuncture as a potentially beneficial approach for the treatment of neurological and neuropsychiatric symptoms, as assessed using clinical scales, and it may have applicability in long COVID patients. Further well-designed clinical studies specifically targeting long COVID patients are needed to validate the role of acupuncture in alleviating long COVID symptoms. Systematic Review Registration: PROSPERO, identifier [CRD42022354940].

The Voltage-Gated Calcium Channel α2δ Subunit in Neuropathic Pain.

Neuropathic pain (NP) is a chronic pain caused by injury or disease of the somatosensory nervous system, or it can be directly caused by disease. It often presents with clinical features like spontaneous pain, hyperalgesia, and dysesthesia. At present, voltage-gated calcium ion channels (VGCCs) are known to be closely related to the development of NP, especially the α2δ subunit. The α2δ subunit is a regulatory subunit of VGCCs. It exists mainly in the brain and peripheral nervous system, especially in nerve cells, and it plays a crucial part in regulating presynaptic and postsynaptic functions. Furthermore, the α2δ subunit influences neuronal excitation and pain signaling by promoting its expression and localization through binding to VGCC-related subunits. The α2δ subunit is widely used in the management of NP as a target of antiepileptic drugs gabapentin and pregabalin. Although drug therapy is one of the treatments for NP, its clinical application is limited due to the adverse reactions caused by drug therapy. Therefore, further research on the therapeutic target α2δ subunit is needed, and attempts are made to obtain an effective treatment for relieving NP without side effects. This review describes the current associated knowledge on the function of the α2δ subunit in perceiving and modulating NP.

Current perspectives and trends of CD39-CD73-eAdo/A2aR research in tumor microenvironment: a bibliometric analysis.

Background and objective: Extracellular adenosine (eAdo) bridges tumor metabolism and immune regulation. CD39-CD73-eAdo/A2aR axis regulates tumor microenvironment (TME) and immunotherapy response. In the era of immunotherapy, exploring the impact of the CD39-CD73-eAdo/A2aR axis on TME and developing targeted therapeutic drugs to enhance the efficacy of immunotherapy are the current research hotspots. This study summarizes and explores the research trends and hotspots of the adenosine axis in the field of TME to provide ideas for further in-depth research. Methods: Literature information was obtained from the Web of Science core collection database. The VOS viewer and the bibliometric tool based on R were used to quantify and identify cooperation information and individual influence by analyzing the detailed information of the global annual publication volume, country/region and institution distribution, article authors and co-cited authors, and journal distribution of these articles. At the same time, the distribution of author keywords and the co-occurrence of author keywords, highly cited articles, and highly co-cited references of CD39-CD73-eAdo/A2aR in the field of TME were analyzed to determine research hotspots and trends. Result: 1,721 articles published in the past ten years were included in this study. Through bibliometric analysis, we found that (1) 69 countries and regions explored the effect of the CD39-CD73-eAdo/A2aR on TME, and the research was generally on the rise. Researchers in the United States dominated research in this area, with the highest total citation rate. China had the most significant number of publications. (2) Harvard University has published the most articles in this field. (3) 12,065 authors contributed to the publication of papers in this field, of which 23 published at least eight papers. STAGG J had significant academic influence, with 24 published articles and 2,776 citations. Co-cited authors can be clustered into three categories. Stagg J, Allard B, Ohta A, and Antonioli, L occupied a central position in the network. (4) 579 scholarly journals have published articles in this field. The journal FRONTIERS IN IMMUNOLOGY published the most significant number of papers, with 97 articles and a total of 2,317 citations, and the number of publications increased year by year. (5) "The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets" was the most frequently local cited article (163 times). The "A2A adenosine receptor protects tumors from antitumor T cells" was the most co-cited reference (224 times). (6) Through the analysis of author keywords, we found that the relationship between adenosine and immunotherapy was a core concept for many researchers in this field. Breast cancer, melanoma, colorectal cancer, ovarian cancer, glioblastoma, pancreatic cancer, hepatocellular carcinoma, and lung cancer were the most frequent cancer types in adenosine-related tumor studies. Immunotherapy, immunosuppression, immune checkpoint, and immune checkpoint inhibitors were the hot keywords in the research, reflecting the importance of the adenosine metabolic pathway in tumor immunotherapy. The keywords such as Immunogenic cell death, T cells, Sting, regulatory T cells, innate immunity, and immune infiltration demonstrated the pathways by which adenosine affected the TME. The famous author keywords in recent years have been immunotherapy, immunogenic cell death, inflammation, lung cancer, and gastric cancer. Conclusion: The effect of CD39-CD73-eAdo/A2aR on the infiltration and function of various immune cells in TME, tumor immunotherapy response, and patient prognosis has attracted the attention of researchers from many countries/regions. American scholars still dominate the research in this field, but Chinese scholars produce the most research results. The journal FRONTIERS IN IMMUNOLOGY has published the wealthiest research in the field. Stagg J was a highly influential researcher in this field. Further exploration of targeted inhibition of CD39-CD73-eAdo/A2aR alone or in combination with other immunotherapy, radiotherapy, and chemotherapy in treating various cancer types and developing effective clinical therapeutic drugs are continuous research hotspots in this field.