Repression of PRMT activities sensitize homologous recombination-proficient ovarian and breast cancer cells to PARP inhibitor treatment.

An "induced PARP inhibitor (PARPi) sensitivity by epigenetic modulation" strategy is being evaluated in the clinic to sensitize homologous recombination (HR)-proficient tumors to PARPi treatments. To expand its clinical applications and identify more efficient combinations, we performed a drug screen by combining PARPi with 74 well-characterized epigenetic modulators that target five major classes of epigenetic enzymes. Both type I PRMT inhibitor and PRMT5 inhibitor exhibit high combination and clinical priority scores in our screen. PRMT inhibition significantly enhances PARPi treatment-induced DNA damage in HR-proficient ovarian and breast cancer cells. Mechanistically, PRMTs maintain the expression of genes associated with DNA damage repair and BRCAness and regulate intrinsic innate immune pathways in cancer cells. Analyzing large-scale genomic and functional profiles from TCGA and DepMap further confirms that PRMT1, PRMT4, and PRMT5 are potential therapeutic targets in oncology. Finally, PRMT1 and PRMT5 inhibition act synergistically to enhance PARPi sensitivity. Our studies provide a strong rationale for the clinical application of a combination of PRMT and PARP inhibitors in patients with HR-proficient ovarian or breast cancer.

A novel Senescence-Based prognostic model unveils tumor interactions and drug resistance in colorectal cancer.

BACKGROUND: In China, CRC incidence is escalating. The main hurdles are heterogeneity and drug resistance. This research delves into cellular senescence in CRC, aiming to devise a prognostic model and pinpoint mechanisms impacting drug resistance. METHODS: Mendelian randomization (MR) analysis confirmed the association between CRC and cellular aging. The Cancer Genome Atlas (TCGA)-CRC data served as the training set, with GSE38832 and GSE39582 as validation sets. Various bioinformatics methods were employed to construct and validate a risk model. CRC cells with NADPH Oxidase 4 (NOX4) knockout were generated using CRISPR-Cas9 technology. Protein blotting and colony formation assays elucidated the role of NOX4 in CRC cell aging and drug resistance. RESULTS: A prognostic model, derived from dataset analysis, uncovered a link between high-risk groups and cancer progression. Notable differences in the tumor microenvironment were observed between risk groups. Finally, NOX4 was found to be linked with aging and drug resistance in CRC. CONCLUSION: This research presents a novel senescence-based CRC prognosis model. It identifies NOX4's role in CRC drug resistance, suggesting it is a potential treatment target.

Long-term exposure to major constituents of fine particulate matter and neurodegenerative diseases: A population-based survey in the Pearl River Delta Region, China.

BACKGROUND: Exposure to PM2.5 has been linked to neurodegenerative diseases, with limited understanding of constituent-specific contributions. OBJECTIVES: To explore the associations between long-term exposure to PM2.5 constituents and neurodegenerative diseases. METHODS: We recruited 148,274 individuals aged ≥ 60 from four cities in the Pearl River Delta region, China (2020 to 2021). We calculated twenty-year average air pollutant concentrations (PM2.5 mass, black carbon (BC), organic matter (OM), ammonium (NH4+), nitrate (NO3-) and sulfate (SO42-)) at the individuals' home addresses. Neurodegenerative diseases were determined by self-reported doctor-diagnosed Alzheimer's disease (AD) and Parkinson's disease (PD). Generalized linear mixed models were employed to explore associations between pollutants and neurodegenerative disease prevalence. RESULTS: PM2.5 and all five constituents were significantly associated with a higher prevalence of AD and PD. The observed associations generally exhibited a non-linear pattern. For example, compared with the lowest quartile, higher quartiles of BC were associated with greater odds for AD prevalence (i.e., the adjusted odds ratios were 1.81; 95% CI, 1.45-2.27; 1.78; 95% CI, 1.37-2.32; and 1.99; 95% CI, 1.54-2.57 for the second, third, and fourth quartiles, respectively). CONCLUSIONS: Long-term exposure to PM2.5 and its constituents, particularly combustion-related BC, OM, and SO42-, was significantly associated with higher prevalence of AD and PD in Chinese individuals. ENVIRONMENTAL IMPLICATION: PM2.5 is a routinely regulated mixture of multiple hazardous constituents that can lead to diverse adverse health outcomes. However, current evidence on the specific contributions of PM2.5 constituents to health effects is scarce. This study firstly investigated the association between PM2.5 constituents and neurodegenerative diseases in the moderately to highly polluted Pearl River Delta region in China, and identified hazardous constituents within PM2.5 that have significant impacts. This study provides important implications for the development of targeted PM2.5 prevention and control policies to reduce specific hazardous PM2.5 constituents.

Prognostic role of urinary ketone body in patients with sepsis-associated encephalopathy without hepatic failure: a retrospective cohort study.

Sepsis-associated encephalopathy (SAE) is defined as a dysfunction of the central nervous system experienced during sepsis with variable clinical features. The study aims to identify the prognostic role of urinary ketone bodies in relation to clinical outcomes in patients with SAE. The Medical Information Mart for Intensive Care III (MIMIC-III) database was used to conduct a retrospective cohort study. We recruited 427 patients with SAE admitted to the intensive care unit (ICU) from the MIMIC-III database. Patients with SAE were divided into a survival group (380 patients) and a non-survival group (47 patients). We used the Wilcoxon signed-rank test and the multivariate logistic regression analysis to analyze the relationship between the level of urinary ketone bodies and the clinical prognosis in patients with SAE. The primary outcome was the relationship between urinary ketone body levels and 28-day mortality of SAE. The secondary outcomes were the relationship between urinary ketone body levels and length of ICU stays, Simplified Acute Physiology Score II, Sequential Organ Failure Assessment (SOFA), Glasgow Coma Scale, mechanical ventilation, renal replacement therapy, and the use of vasopressors. The 28-day mortality of patients with SAE was 11.0%. Urinary ketone body levels were not significantly associated with the 28-day mortality of patients with SAE. Urinary ketone body levels were associated with SOFA score and the use of vasopressors in patients with SAE. The SOFA score was an independent risk factor for the 28-day mortality in patients with SAE. Urinary ketone body levels were significantly associated with SOFA score and the use of vasopressors in patients with SAE. Furthermore, the SOFA score can predict the prognosis of short-term outcomes of patients with SAE. Therefore, we should closely monitor the changes of urinary ketone bodies and SOFA score and intervene in time.

Deciphering alternative splicing events and their therapeutic implications in colorectal Cancer.

Colorectal cancer (CRC) is one of the most common malignant tumors with complex molecular regulatory mechanisms. Alternative splicing (AS), a fundamental regulatory process of gene expression, plays an important role in the occurrence and development of CRC. This study analyzed AS Percent Spliced In (PSI) values from 49 pairs of CRC and normal samples in the TCGA SpliceSeq database. Using Lasso and SVM, AS features that can differentiate colorectal cancer from normal were screened. Univariate COX regression analysis identified prognosis-related AS events. A risk model was constructed and validated using machine learning, Kaplan-Meier analysis, and Decision Curve Analysis. The regulatory effect of protein arginine methyltransferase 5 (PRMT5) on poly(RC) binding protein 1 (PCBP1) was verified by immunoprecipitation experiments, and the effect of PCBP1 on the AS of Obscurin (OBSCN) was verified by PCR. Five AS events, including HNF4A.59461.AP and HNF4A.59462.AP, were identified, which can distinguish CRC from normal tissue. A machine learning model using 21 key AS events accurately predicted CRC prognosis. High-risk patients had significantly shorter survival times. PRMT5 was found to regulate PCBP1 function and then influence OBSCN AS, which may drive CRC progression. The study concluded that some AS events is significantly different in CRC and normal tissues, and some of these AS events are related to the prognosis of CRC. In addition, PRMT family-driven arginine modifications play an important role in CRC-specific AS events.

Hsa_circ_0007990 promotes breast cancer growth via inhibiting YBX1 protein degradation to activate E2F1 transcription.

Breast cancer (BC) is the most commonly diagnosed malignant tumour in females worldwide. Although remarkable advances in early detection and treatment strategies have led to decreased mortality, recurrence and metastasis remain the major causes of cancer death in BC patients. Increasing evidence has demonstrated that circular RNAs (circRNAs) play critical roles in cancer progression. However, the detailed biological functions and molecular mechanisms of circRNAs in BC are unclear. The aim of this study was to investigate the possible role of circRNAs in the progression of BC. Differentially expressed circRNAs in BC were identified by integrating breast tumour-associated somatic CNV data and circRNA high-throughput sequencing. Aberrant hsa_circ_0007990 expression and host gene copy number were detected in BC cell lines via quantitative polymerase chain reaction (qPCR). The expression level of hsa_circ_0007990 in BC tissues was validated by in situ hybridization (ISH). Loss- and gain-of-function experiments were performed in vitro and in vivo, respectively, to explore the potential biological function of hsa_circ_0007990 in BC. The underlying mechanisms of hsa_circ_0007990 were investigated through MS2 RNA pull-down, RNA immunoprecipitation, RNA fluorescence in situ hybridization, immunofluorescence, chromatin immunoprecipitation and luciferase reporter assays. The levels of hsa_circ_0007990 were elevated in BC tissues and cell lines, an effect that was partly due to host gene copy number gains. Functional assays showed that hsa_circ_0007990 promoted BC cell growth. Mechanistically, hsa_circ_0007990 could bind to YBX1 and inhibit its degradation by preventing ubiquitin/proteasome-dependent degradation, thus enhancing the expression of the cell cycle-associated gene E2F1. Rescue experiments suggested that hsa_circ_0007990 promoted BC progression through YBX1. In general, our study demonstrated that hsa_circ_0007990 modulates the ubiquitination and degradation of YBX1 protein and further regulates E2F1 expression to promote BC progression. We explored the possible function and molecular mechanism of hsa_circ_0007990 in BC and identified a novel candidate target for the treatment of BC.

Field test of quantum key distribution over aerial fiber based on simple and stable modulation.

We have developed a simple time-bin phase encoding quantum key distribution system, using the optical injection locking technique. This setup incorporates both the merits of simplicity and stability in encoding, and immunity to channel disturbance. We have demonstrated the field implementation of quantum key distribution over long-distance deployed aerial fiber automatically. During the 70-day field test, we achieved approximately a 1.0 kbps secure key rate with stable performance. Our work takes an important step toward widespread implementation of QKD systems in diverse and complex real-life scenarios.

Time-bin phase-encoding quantum key distribution using Sagnac-based optics and compatible electronics.

In this work, we present a new time-bin phase-encoding quantum key distribution (QKD), where the transmitter utilizes an inherently stable Sagnac-type interferometer, and has comparable electrical requirements to existing polarization or phase encoding schemes. This approach does not require intensity calibration and is insensitive to environmental disturbances, making it both flexible and high-performing. We conducted experiments with a compact QKD system to demonstrate the stability and secure key rate performance of the presented scheme. The results show a typical secure key rate of 6.2 kbps@20 dB and 0.4 kbps@30 dB with channel loss emulated by variable optical attenuators. A continuous test of 120-km fiber spool shows a stable quantum bit error rate of the time-bin basis within 0.4%∼0.6% over a consecutive 9-day period without any adjustment. This intrinsically stable and compatible scheme of time-bin phase encoding is extensively applicable in various QKD experiments, including BB84 and measurement-device-independent QKD.

A Silver Lining of Neuropathic Pain: Predicting Favorable Functional Outcome in Spinal Cord Injury.

Background: Neuropathic pain (NP) is a common and severe problem following spinal cord injury (SCI). However, its relationship with functional outcome remains unclear. Methods: A retrospective explorative analysis was performed on SCI patients admitted to a tertiary academic medical center between January 2018 and June 2022. The candidate predictor variables, including demographics, clinical characteristics and complications, were analyzed with logistic and linear regression. Spinal Cord Independence Measure (SCIM) scores at discharge and mean relative functional gain (mRFG) of SCIM were as outcome parameters. Results: A total of 140 SCI patients included for the final analysis. Among them, 44 (31.43%) patients were tetraplegics, and 96 (68.57%) patients were paraplegics; 68 (48.57%) patients developed NP, and 72 (51.43%) patients did not. Logistic and linear regression analyses of SCIM at discharge both showed that NP [OR=3.10, 95% CI (1.29,7.45), P=0.01; unstandardized ß=11.47, 95% CI (4.95,17.99), P<0.01; respectively] was significantly independent predictors for a favorable outcome (SCIM at discharge ≥ 50, logistic regression results) and higher SCIM total score at discharge (linear regression results). Besides, NP [unstandardized ß=15.67, 95% CI (8.94,22.41), P<0.01] was also independently associated with higher mRFG of SCIM scores. Furthermore, the NP group had significantly higher mRFG, SCIM total scores and subscales (self-care, respiration and sphincter management, and mobility) at discharge compared to the non-NP group. However, there were no significant differences in mRFG, SCIM total score or subscales at discharge among the NP subgroups in terms of locations (at level pain, below level pain, and both) or timing of occurrence (within and after one month after SCI). This study also showed that incomplete injury, lumbar-sacral injury level and non-anemia were significantly independent predictors for a favorable outcome, and higher mRFG of SCIM scores (except for non-anemia). Conclusion: NP appears independently associated with better functional recovery in SCI patients, suggesting the bright side of this undesirable complication. These findings may help to alleviate the psychological burden of NP patients and ultimately restore their confidence in rehabilitation.

Nomogram for predicting the unfavourable outcomes of percutaneous endoscopic transforaminal discectomy for lumbar disc herniation: a retrospective study.

Objective: To investigate and integrate multiple independent risk factors to establish a nomogram for predicting the unfavourable outcomes of percutaneous endoscopic transforaminal discectomy (PETD) for lumbar disc herniation (LDH). Methods: From January 2018 to December 2019, a total of 425 patients with LDH undergoing PETD were included in this retrospective study. All patients were divided into the development and validation cohort at a ratio of 4:1. Univariate and multivariate logistic regression analyses were used to investigate the independent risk factors associated with the clinical outcomes of PETD for LDH in the development cohort, and a prediction model (nomogram) was established to predict the unfavourable outcomes of PETD for LDH. In the validation cohort, the nomogram was validated by the concordance index (C-index), calibration curve, and decision curve analysis (DCA). Results: 29 of 340 patients showed unfavourable outcomes in the development cohort, and 7 of 85 patients showed unfavourable outcomes in the validation cohort. Body mass index (BMI), course of disease (COD), protrusion calcification (PC), and preoperative lumbar epidural steroid injection (LI) were independent risk factors associated with the unfavourable outcomes of PETD for LDH and were identified as predictors for the nomogram. The nomogram was validated by the validation cohort and showed high consistency (C-index = 0.674), good calibration and high clinical value. Conclusions: The nomogram based on patients' preoperative clinical characteristics, including BMI, COD, LI and PC, can be used to accurately predict the unfavourable outcomes of PETD for LDH.

Primary motor hand area corticospinal excitability indicates overall functional recovery after spinal cord injury.

Background: After spinal cord injury (SCI), the excitability of the primary motor cortex (M1) lower extremity area decreases or disappears. A recent study reported that the M1 hand area of the SCI patient encodes the activity information of both the upper and lower extremities. However, the characteristics of the M1 hand area corticospinal excitability (CSE) changes after SCI and its correlation with extremities motor function are still unknown. Methods: A retrospective study was conducted on the data of 347 SCI patients and 80 healthy controls on motor evoked potentials (MEP, reflection of CSE), extremity motor function, and activities of daily living (ADL) ability. Correlation analysis and multiple linear regression analysis were conducted to analyze the relationship between the degree of MEP hemispheric conversion and extremity motor function/ADL ability. Results: The CSE of the dominant hemisphere M1 hand area decreased in SCI patients. In 0-6 m, AIS A grade, or non-cervical injury SCI patients, the degree of M1 hand area MEP hemispheric conversion was positively correlated with total motor score, lower extremity motor score (LEMS), and ADL ability. Multiple linear regression analysis further confirmed the contribution of MEP hemispheric conversion degree in ADL changes as an independent factor. Conclusion: The closer the degree of M1 hand area MEP hemispheric conversion is to that of healthy controls, the better the extremity motor function/ADL ability patients achieve. Based on the law of this phenomenon, targeted intervention to regulate the excitability of bilateral M1 hand areas might be a novel strategy for SCI overall functional recovery.

lncSNHG3 drives breast cancer progression by epigenetically increasing CSNK2A1 expression level.

Mounting evidence demonstrates that long noncoding RNAs (lncRNAs) have critical roles in the initiation and progression of cancer. Here, we report that small nucleolar RNA host gene 3 (SNHG3) is a key regulator of breast cancer progression. We analyzed RNA sequencing data to explore abnormally expressed lncRNAs in breast cancer. The effects of SNHG3 on breast cancer were investigated via in vitro and in vivo assays (CCK-8 assay, colony formation assay, flow cytometry assay, EdU assay, xenograft model, immunohistochemistry, and Western blot). The mechanism of SNHG3 action was explored through bioinformatics, RNA fluorescence in situ hybridization, luciferase reporter assay, RNA pull-down assay, chromatin immunoprecipitation assay and RNA immunoprecipitation assay. We found that SNHG3 expression was upregulated in breast cancer tissues and that its high expression level was associated with poor survival. We also found that high SNHG3 expression was partly induced by STAT3. Moreover, SNHG3 knockdown significantly repressed breast cancer cell growth both in vitro and in vivo. In the cytoplasm, SNHG3 facilitated the expression of Casein kinase II-A1 (CSNK2A1) by absorbing miR-485-5p and recruiting the HuR protein, participating in the malignant progression of breast cancer. Taken together, our study reveals a SNHG3-based regulatory network, which plays an oncogenic role in breast cancer and suggests that SNHG3 may serve as a potential target for the diagnosis and treatment of breast cancer.

A novel prognostic signatures based on metastasis- and immune-related gene pairs for colorectal cancer.

Background: Metastasis remains the leading cause of mortality in patients diagnosed with colorectal cancer (CRC). The pivotal contribution of the immune microenvironment in the initiation and progression of CRC metastasis has gained significant attention. Methods: A total of 453 CRC patients from The Cancer Genome Atlas (TCGA) were included as the training set, and GSE39582, GSE17536, GSE29621, GSE71187 were included as the validation set. The single-sample gene set enrichment analysis (ssGSEA) was performed to assess the immune infiltration of patients. Least absolute shrinkage and selection operator (LASSO) regression analysis, Time-dependent receiver operating characteristic (ROC) and Kaplan-Meier analysis were used to construct and validate risk models based on R package. CTSW and FABP4-knockout CRC cells were constructed via CRISPR-Cas9 system. Western-blot and Transwell assay were utilized to explore the role of fatty acid binding protein 4 (FABP4) / cathepsin W (CTSW) in CRC metastasis and immunity. Results: Based on the normal/tumor, high-/low-immune cell infiltration, and metastatic/non-metastatic group, we identified 161 differentially expressed genes. After random assignment and LASSO regression analysis, a prognostic model containing 3 metastasis- and immune-related gene pairs was constructed and represented good prognostic prediction efficiency in the training set and 4 independent CRC cohorts. According to this model, we clustered patients and found that the high-risk group was associated with stage, T and M stage. In addition, the high-risk group also shown higher immune infiltration and high sensitivity to PARP inhibitors. Further, FABP4 and CTSW derived from the constitutive model were identified to be involved in metastasis and immunity of CRC. Conclusion: In conclusion, a validated prognosis predictive model for CRC was constructed. CTSW and FABP4 are potential targets for CRC treatment.

Metagenomic analysis to determine the characteristics of antibiotic resistance genes in typical antibiotic-contaminated sediments.

Comprehensive studies of the effects of various physical and chemical variables (including heavy metals), antibiotics, and microorganisms in the environment on antibiotic resistance genes are rare. We collected sediment samples from the Shatian Lake aquaculture area and surrounding lakes and rivers located in Shanghai, China. The spatial distribution of sediment ARGs was assessed by metagenomic analysis that revealed 26 ARG types (510 subtypes), dominated by Multidrug, ß-lactam, Aminoglycoside, Glycopeptides, Fluoroquinolone, and Tetracyline. Redundancy discriminant analysis indicated that antibiotics (SAs and MLs) in the aqueous environment and sediment along with water TN and TP were the key variables affecting the abundance distribution of total ARGs. However, the main environmental drivers and key influences differed among the different ARGs. For total ARGs, the environmental subtypes affecting their structural composition and distribution characteristics were mainly antibiotic residues. Procrustes analysis showed a significant correlation between ARGs and microbial communities in the sediment in the survey area. Network analysis revealed that most of the target ARGs were significantly and positively correlated with microorganisms, and a small number of ARGs (e.g., rpoB, mdtC, and efpA) were highly significantly and positively correlated with microorganisms (e.g., Knoellia, Tetrasphaera, and Gemmatirosa). Potential hosts for the major ARGs included Actinobacteria, Proteobacteria, and Gemmatimonadetes. Our study provides new insight and a comprehensive assessment of the distribution and abundance of ARGs and the drivers of ARG occurrence and transmission.

Screening for PTSD and TBI in Veterans using Routine Clinical Laboratory Blood Tests.

Post-traumatic stress disorder (PTSD) is a mental disorder diagnosed by clinical interviews, self-report measures and neuropsychological testing. Traumatic brain injury (TBI) can have neuropsychiatric symptoms similar to PTSD. Diagnosing PTSD and TBI is challenging and more so for providers lacking specialized training facing time pressures in primary care and other general medical settings. Diagnosis relies heavily on patient self-report and patients frequently under-report or over-report their symptoms due to stigma or seeking compensation. We aimed to create objective diagnostic screening tests utilizing Clinical Laboratory Improvement Amendments (CLIA) blood tests available in most clinical settings. CLIA blood test results were ascertained in 475 male veterans with and without PTSD and TBI following warzone exposure in Iraq or Afghanistan. Using random forest (RF) methods, four classification models were derived to predict PTSD and TBI status. CLIA features were selected utilizing a stepwise forward variable selection RF procedure. The AUC, accuracy, sensitivity, and specificity were 0.730, 0.706, 0.659, and 0.715, respectively for differentiating PTSD and healthy controls (HC), 0.704, 0.677, 0.671, and 0.681 for TBI vs. HC, 0.739, 0.742, 0.635, and 0.766 for PTSD comorbid with TBI vs HC, and 0.726, 0.723, 0.636, and 0.747 for PTSD vs. TBI. Comorbid alcohol abuse, major depressive disorder, and BMI are not confounders in these RF models. Markers of glucose metabolism and inflammation are among the most significant CLIA features in our models. Routine CLIA blood tests have the potential for discriminating PTSD and TBI cases from healthy controls and from each other. These findings hold promise for the development of accessible and low-cost biomarker tests as screening measures for PTSD and TBI in primary care and specialty settings.

Clinical efficacy of transforaminal endoscopic discectomy in the treatment of recurrent lumbar disc herniation: a single-center retrospective analysis.

PURPOSE: To investigate the clinical efficacy of transforaminal endoscopic discectomy (TED) in treating recurrent lumbar disc herniation. METHODS: Clinical datal of 31 patients who were hospitalized in the Department of Pain Management, First Affiliated Hospital of Nanchang University, between 2015 and 2018 due to recurrent lumbar disc herniation were collected and analyzed retrospectively. Visual analogue scale (VAS) scores and Japanese Orthopedic Association (JOA) scores were used to assess alterations of patients' leg pain intensity and nerve function, respectively. The Modified MacNab criteria were used to evaluate patients' excellent and good rates. RESULTS: Compared to clinical data before surgery, there was a significant reduction in VAS scores (P < 0.01) along with a significant improvement in JOA scores (P < 0.01) at 2 years after revision surgery. The patients' excellent and good rates were 83.9% at the 2 years after surgery. CONCLUSION: The TED is safe and effective in the long term and is applicable to the treatment of recurrent lumbar disc herniation.

Circular RNA circ0104103 inhibits colorectal cancer progression through interactions with HuR and miR-373-5p.

Emerging evidence has suggested that circular RNAs (circRNAs) have vital functions during the initiation and progression of various diseases. However, circRNA potential mechanisms in colorectal cancer (CRC) are largely unknown. Here, we sought to investigate the role and underlying regulatory mechanism of circ0104103 in CRC. circ0104103 was validated by quantitative RT-PCR (qRT-PCR) and Sanger sequencing. Gain- and loss-of-function assays in cell lines and mouse xenograft models were utilized to investigate the effects of circ0104103 in CRC. RNA pull-down assays, RNA immunoprecipitation assays, bioinformatics analyses, RNA FISH, and luciferase reporter assays were used to elucidate the potential mechanism of circ0104103 in CRC. We identified circ0104103, which is strongly downregulated in CRC tissues and cell lines. Functional studies revealed that circ0104103 inhibited CRC cell growth, migration, and invasion both in vitro and in vivo. Mechanistically, circ0104103 binds to HuR, a functional RNA-binding protein commonly expressed in CRC. HuR binds to the 3'UTR of LACTB mRNA to facilitate stabilization and increase its expression. Moreover, circ0104103 was verified as a competing endogenous RNA (ceRNA) via negative regulation of miR-373-5p to increase LACTB expression, resulting in inhibiting the occurrence and progression of CRC. Taken together, our study revealed that circ0104103 acts as a tumor suppressor and may be a novel biomarker and therapeutic target in CRC.

Building a personalized patient education model for general practice by Delphi method.

BACKGROUND: As one of the 3 strategic measures for disease prevention and control in the 21st century identified by WHO, patient education is the most effective measure to change people's behaviour and lifestyle. However, there are many problems with patient education in general practice in China. Because there is no suitable and uniform mode of patient education for the busy and crowded Chinese general practice. Therefore, it is necessary to establish an appropriate personalized patient education model. METHODS: There were 3 rounds of consultation of the Delphi method. Each round of consultation is adjusted, modified, or deleted based on the previous round according to the degree of concentration and coordination of expert opinions. Thus form the index system of personalized patient education model. Using Cronbach α to conduct an internal consistency test for the index system. RESULTS: Twenty-three participants participated in the study. The effective recovery rate of consultation was 100%. In the third round of consultation, the variation importance coefficient was 0-0.25, the variation operability coefficient was 0.07-0.26. Kendall's W of importance and operability score was significant (Kendall's W = 0.186; P < 0.01). The chi-square test result of importance is (X2 = 232.744) and operability is (X2 = 246.156). The Cronbach α was 0.974. EFA (exploratory factor analysis) indicates the model has good construct validity. CONCLUSIONS: The CAPDCA personalized patient education model was preliminarily constructed in this study. Specifically, 6 first-level indicators including collection (C), assessment (A), plan (P), do (D), check (C), aggrandizement (A), 24 second-level indicators, and 34 third-level indicators. That forms the cyclic personalized patient education paradigm which has reasonable structure and high feasibility.

Recent advances in small molecule inhibitors of interleukin‑1 receptor-associated kinase / 药学学报

Interleukin-1 receptor associated kinase 4 (IRAK-4), acting as a serine threonine kinase, is considered as a key signal node for the transduction of IL-1R family and TLRs signal pathway. Studies have found that IRAK-4 has a hand in many signal pathways, involving the inflammatory response of human joints, intestines, liver and nervous system, as well as other autoimmune diseases. It is also one of the causes of drug resistance of some cancer cells. Therefore, IRAK-4 tends to be an effective therapeutic target for inflammatory diseases and cancer. The prospects for the development of drugs in this pathway is to develop novel IRAK-4 small molecule inhibitors and investigate their safety and effectiveness, enrich the clinical treatment of inflammatory and cancer diseases finally. This paper classified and summarized the latest research progress on small molecule inhibitors of IRAK-4 signaling pathway according to structures of the compounds, in order to provide assistances and references for the research and development of related drugs.