Acute Pancreatitis in Pregnancy: A Propensity Score Matching Analysis and Dynamic Nomogram for Risk Assessment.

BACKGROUND: Acute pancreatitis is easily confused with abdominal pain symptoms, and it could lead to serious complications for pregnant women and fetus, the mortality was as high as 3.3% and 11.6-18.7%, respectively. However, there is still lack of sensitive laboratory markers for early diagnosis of APIP and authoritative guidelines to guide treatment. OBJECTIVE: The purpose of this study was to explore the risk factors of acute pancreatitis in pregnancy, establish, and evaluate the dynamic prediction model of risk factors in acute pancreatitis in pregnancy patients. STUDY DESIGN: Clinical data of APIP patients and non-pregnant acute pancreases patients who underwent regular antenatal check-ups during the same period were collected. The dataset after propensity matching was randomly divided into training set and verification set at a ratio of 7:3. The model was constructed using Logistic regression, least absolute shrinkage and selection operator regression, R language and other methods. The training set model was used to construct the diagnostic nomogram model and the validation set was used to validate the model. Finally, the accuracy and clinical practicability of the model were evaluated. RESULTS: A total of 111 APIP were included. In all APIP patients, hyperlipidemic pancreatitis was the most important reason. The levels of serum amylase, creatinine, albumin, triglyceride, high-density lipoprotein cholesterol, and apolipoprotein A1 were significantly different between the two groups. The propensity matching method was used to match pregnant pancreatitis patients and pregnant non-pancreatic patients 1:1 according to age and gestational age, and the matching tolerance was 0.02. The multivariate logistic regression analysis of training set showed that diabetes, triglyceride, Body Mass Index, white blood cell, and C-reactive protein were identified and entered the dynamic nomogram. The area under the ROC curve of the training set was 0.942 and in validation set was 0.842. The calibration curve showed good predictive in training set, and the calibration performance in the validation set was acceptable. The calibration curve showed the consistency between the nomogram model and the actual probability. CONCLUSION: The dynamic nomogram model we constructed to predict the risk factors of acute pancreatitis in pregnancy has high accuracy, discrimination, and clinical practicability.

Sb/As immobilization and soil function improvement under the combined remediation strategy of modified biochar and Sb-oxidizing bacteria at a smelting site.

Antimony (Sb) and arsenic (As) lead to soil pollution and structural degradation at Sb smelting sites. However, most sites focus solely on Sb/As immobilization, neglecting the restoration of soil functionality. Here, we investigated the effectiveness of Fe/H2O2 modified biochar (Fe@H2O2-BC) and Sb-oxidizing bacteria (Bacillus sp. S3) in immobilizing Sb/As and enhancing soil functional resilience at an Sb smelting site. Over a twelve-month period, the leaching toxicity of As and Sb was reduced to 0.05 and 0.005 mg L-1 (GB3838-2002) respectively, with 1% (w/w) Fe@H2O2-BC and 2% (v/v) Bacillus sp. S3 solution. Compared to CK, the combination of Fe@H2O2-BC and Bacillus sp. S3 significantly reduced the bioavailable As/Sb by 98.00%/93.52%, whilst increasing residual As and reducible Sb fractions by 210.31% and 96.51%, respectively. The combined application generally improved soil aggregate structure, pore characteristics, and water-holding capacity. Fe@H2O2-BC served as a pH buffer and long-term reservoir of organic carbon, changing the availability of carbon substrates to bacteria. The inoculation of Bacillus sp. S3 facilitated the transformation of Sb(III)/As(III) to Sb(V)/As(V) and differentiated the composition and functional roles of bacterial communities in soils. The combination increased the abundance of soil saprotrophs by 164.20%, whilst improving the relative abundance of N- and S-cycling bacteria according to FUNGuild and FAPROTAX analysis. These results revealed that the integrated application was instrumental in As/Sb detoxification/immobilization and soil function restoration, which demonstrating a promising microbially-driven ecological restoration strategy at Sb smelting sites.

Prediction and evaluation of a nomogram model for recurrent acute pancreatitis.

OBJECTIVE: The purpose of this study was to investigate the influencing factors for recurrent acute pancreatitis and construct the nomogram model to predict the risk of recurrent acute pancreatitis. METHODS: Patients diagnosed with acute pancreatitis in the Affiliated Hospital of Southwest Medical University were enrolled. We collected these patients' basic information, laboratory data, imaging information. Using Logistic regression and least absolute shrinkage and selection operator regression to select risk factor for Cross-Validation Criterion. To create nomogram and validated by receiver operator characteristic curve, calibration curves and decision curve analysis. RESULTS: A total of 533 patients with acute pancreatitis were included, including 99 recurrent acute pancreatitis patients. The average age of recurrent acute pancreatitis patients was 49.69 years old, and 67.7% of them were male. At the same time, in all recurrent acute pancreatitis patients, hypertriglyceridemic pancreatitis is the most important reason (54.5%). Regression analysis and least absolute shrinkage and selection operator regression showed that smoking history, acute necrotic collection, triglyceride, and alcohol etiology for acute pancreatitis were identified and entered into the nomogram. The area under the receiver operator characteristic curve of the training set was 0.747. The calibration curve showed the consistency between the nomogram model and the actual probability. CONCLUSION: In conclusion, some high-risk factors like smoking history, acute necrotic collection, triglyceride, and alcohol etiology for acute pancreatitis may predict recurrent pancreatitis and their incorporation into a nomogram has high accuracy in predicting recurrence.

A COX2-targeting cancer-specific fluorescent probe for hydrogen sulfide detection in living cells, Caenorhabditis elegans, and zebrafish.

A novel cyclooxygenase-2 (COX-2) targeted H2S-activated cancer-specific fluorescent probe, namely, COX2-H2S, was designed and synthesized, with naphthalimide as the fluorophore and indomethacin as the targeting group. This H2S-sensing probe was developed to differentiate tumor cells from normal cells and was tested in living cells, Caenorhabditis elegans (C. elegans), and zebrafish. The probe could successfully be used for imaging endogenous and exogenous H2S in living cells, demonstrating high sensitivity and specificity and strong anti-interference. COX2-H2S had the ability to not only discern cancer cells from normal cells but also specifically recognize 9L/lacZ cells from other glioblastoma cells (U87-MG and LN229). It could also be successfully applied for the fluorescent live imaging of H2S in both C. elegans and zebrafish.

Trends of hospitalisation among new admission inpatients with oesophagogastric variceal bleeding in cirrhosis from 2014 to 2019 in the Affiliated Hospital of Southwest Medical University: a single-centre time-series analysis.

OBJECTIVES: This study aimed to assess the internal law and time trend of hospitalisation for oesophagogastric variceal bleeding (EGVB) in cirrhosis and develop an effective model to predict the trend of hospitalisation time. DESIGN: We used a time series covering 72 months to analyse the hospitalisation for EGVB in cirrhosis. The number of inpatients in the first 60 months was used as the training set to establish the autoregressive integrated moving average (ARIMA) model, and the number over the next 12 months was used as the test set to predict and observe their fitting effect. SETTING AND DATA: Case data of patients with EGVB between January 2014 and December 2019 were collected from the Affiliated Hospital of Southwest Medical University. OUTCOME MEASURES: The number of monthly hospitalised patients with EGVB in our hospital. RESULTS: A total of 877 patients were included in the analysis. The proportion of EGVB in patients with cirrhosis was 73% among men and 27% among women. The peak age at hospitalisation was 40-60 years. The incidence of EGVB varied seasonally with two peaks from January to February and October to November, while the lowest number was observed between April and August. Time-series analysis showed that the number of inpatients with EGVB in our hospital increased annually. The sequence after the first-order difference was a stationary series (augmented Dickey-Fuller test p=0.02). ARIMA (0,1,0) (0,1,1)12 with a minimum Akaike Information Criterion value of 260.18 could fit the time trend of EGVB inpatients and had a good short-term prediction effect. The root mean square error and mean absolute error were 2.4347 and 1.9017, respectively. CONCLUSIONS: The number of hospitalised patients with EGVB at our hospital is increasing annually, with seasonal changes. The ARIMA model has a good prediction effect on the number of hospitalised patients with EGVB in cirrhosis.

Role of sestrins in metabolic and aging-related diseases.

Sestrins are a type of highly conserved stress-inducing protein that has antioxidant and mTORC1 inhibitory functions. Metabolic dysfunction and aging are the main risk factors for development of human diseases, such as diabetes, neurodegenerative diseases, and cancer. Sestrins have important roles in regulating glucose and lipid metabolism, anti-tumor functions, and aging by inhibiting the reactive oxygen species and mechanistic target of rapamycin complex 1 pathways. In this review, the structure and biological functions of sestrins are summarized, and how sestrins are activated and contribute to regulation of the downstream signal pathways of metabolic and aging-related diseases are discussed in detail with the goal of providing new ideas and therapeutic targets for the treatment of related diseases.

Betaine eliminates CFA-induced depressive-like behaviour in mice may be through inhibition of microglia and astrocyte activation and polarization.

Chronic pain can induce not only nociceptive but also depressive emotions. A previous study demonstrated that betaine, a commonly used nutrient supplement, has an anti-nociceptive effect, but whether betaine can alleviate chronic pain-induced depressive emotion is elusive. Our current study found that betaine administration significantly eliminated complete Freund's adjuvant (CFA)-induced pain-related depressive-like behaviour. Mechanistically, betaine treatment inhibited microglia and astrocyte activation. Furthermore, betaine significantly promoted the transition of microglia from the M1 to the M2 phenotype, as well as the transition of astrocytes from the A1 to the A2 phenotype. Additionally, the release of pro-inflammatory factors such as IL-18, IL-1ß and IL-6 and anti-inflammatory factors such as IL-10 in the hippocampus induced by CFA were also reversed by betaine administration. Overall, betaine has therapeutic effects on pain-related depressive-like phenotypes caused by CFA, possibly through altering the polarization of microglia and astrocytes to reduce neuroinflammation.

Unlocking the Therapeutic Potential of Exosomes Derived From Nasal Olfactory Mucosal Mesenchymal Stem Cells: Restoring Synaptic Plasticity, Neurogenesis, and Neuroinflammation in Schizophrenia.

BACKGROUND AND HYPOTHESIS: Schizophrenia (SCZ) is a multifaceted mental disorder marked by a spectrum of symptoms, including hallucinations, delusions, cognitive deficits, and negative symptoms. Its etiology involves intricate interactions between genetic and environmental factors, posing significant challenges for effective treatment. We hypothesized that intranasal administration of exosomes derived from nasal olfactory mucosal mesenchymal stem cells (OM-MSCs-exos) could alleviate SCZ-like behaviors in a murine model induced by methylazoxymethanol (MAM). STUDY DESIGN: We conducted a comprehensive investigation to assess the impact of intranasally delivered OM-MSC-exos on SCZ-like behaviors in MAM-induced mice. This study encompassed behavioral assessments, neuroinflammatory markers, glial activation, synaptic protein expression, and neurogenesis within the hippocampus. STUDY RESULTS: Our findings demonstrated that intranasal administration of OM-MSC-exos effectively ameliorated SCZ-like behaviors, specifically addressing social withdrawal and sensory gating deficits in the MAM-induced murine model. Furthermore, OM-MSC-exos intervention yielded a reduction in neuroinflammatory markers and a suppression of microglial activation within the hippocampus. Simultaneously, we observed an upregulation of key synaptic protein expression, including PSD95 and TH, the rate-limiting enzyme for dopamine biosynthesis. CONCLUSIONS: Our study underscores the therapeutic potential of OM-MSC-exos in mitigating SCZ-like behavior. The OM-MSC-exos have the capacity to modulate glial cell activation, diminish neuroinflammation, and promote BDNF-associated synaptic plasticity and neurogenesis, thus ameliorating SCZ-like behaviors. In summary, intranasal administration of OM-MSC-exos offers a multifaceted approach to address SCZ mechanisms, promising innovative treatments for this intricate disorder.

Identification of ACBD3 as a new molecular biomarker in pan-cancers through bioinformatic analysis: a preclinical study.

BACKGROUND: Acyl-CoA-binding domain-containing 3 (ACBD3) is a multifunctional protein, that plays essential roles in cellular signaling and membrane domain organization. Although the precise roles of ACBD3 in various cancers remain unclear. Thus, we aimed to determine the diverse roles of ACBD3 in pan-cancers. METHODS: Relevant clinical and RNA-sequencing data for normal tissues and 33 tumors from The Cancer Genome Atlas (TCGA) database, the Human Protein Atlas, and other databases were applied to investigate ACBD3 expression in various cancers. ACBD3-binding and ACBD3-related target genes were obtained from the STRING and GEPIA2 databases. The possible functions of ACBD3-binding genes were explored using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We also applied the diagnostic value and survival prognosis analysis of ACBD3 in pan-cancers using R language. The mutational features of ACBD3 in various TCGA cancers were obtained from the cBioPortal database. RESULTS: When compared with normal tissues, ACBD3 expression was statistically upregulated in eleven cancers and downregulated in three cancers. ACBD3 expression was remarkably different among various pathological stages of tumors, immune and molecular subtypes of cancers, cancer phosphorylation levels, and immune cell infiltration. The survival of four tumors was correlated with the expression level of ACBD3, including pancreatic adenocarcinoma, adrenocortical carcinoma, sarcoma, and glioma. The high accuracy in diagnosing multiple tumors and its correlation with prognosis indicated that ACBD3 may be a potential biomarker of pan-cancers. CONCLUSION: According to our pan-cancer analysis, ACBD3 may serve as a remarkable prognostic and diagnostic biomarker of pan-cancers as well as contribute to tumor development. ACBD3 may also provide new directions for cancer treatment targets in the future.

Gender authorship trends of gastric cancer in the top journals of gastroenterology: A 20-year perspective.

Gender authorship trends have been explored in varied medical specialties, and no study had observed in the field of gastric cancer. Therefore, we aimed to access whether the "gender gap" in authorship existed in gastric cancer in the leading gastroenterological journals over the last 2 decades. All original articles published from 2000 to 2020 in 9 leading gastroenterological journals were collected. Information on the first and senior author's gender, country of author's institution, and impact factor of journals were collected. Chi-square tests and multivariable logistic regression were used for data analysis. A total of 5785 original articles were included and analyzed, of which 440 (7.61%) were articles on gastric cancer and 5345 (92.39%) covered other topics. Fewer female authors published original articles as first (19.32%, 85/440) and senior authors (14.32%, 63/440) compared with males. Remarkably, a significant increase in female authorship was discovered. The proportion of female first authors grown from 12.99% to 30.89% during the last 20 years (P < .001), but not in senior authors (P = .175). Multivariable logistic analysis showed that female first authors demonstrated a higher percentage when senior authors were female (odds ratio, 2.040; 95% confidence interval, 1.105-3.769). Although a statistically ascending tendency in female first authors on gastric cancer has been going on over the last 20 years, the exorbitant gender gap still exists. This gap may help explain the continued underrepresentation of women within both clinical work and academic research, and prompt us to look further for the underlying causes.

Trends in gender disparity in the field of Helicobacter pylori research from 2000 to 2020: A cross-sectional study.

Many studies have investigated gender disparity in scientific publications, but this has been poorly studied in the field of digestive diseases. This study aimed to determine the gender difference of first and senior authors in publications related to Helicobacter pylori (H. pylori) during the past 20 years. Data were derived from original articles published in the main journals of digestive diseases (Journal of Hepatology, Gut, Gastroenterology, American Journal of Gastroenterology, Endoscopy, Gastrointestinal Endoscopy, Alimentary Pharmacology and Therapeutics, Digestive Endoscopy, Journal of Gastroenterology, Helicobacter, and Gastric Cancer) in 2000, 2005, 2010, 2015, and 2020. These original articles were classified according to the gender and nationality of the first and senior (last listed) authors. Linear-by-linear association test was used to analyze the proportion of women authors over time. Multivariable logistic regression was applied to explain the factors impacting authorship difference of first and senior authors. A total of 561 original articles on H. pylori were collected for this study, accounting for 10.70% in 2000 to 7.60% in 2020 among all articles. In these original articles, the percentage of women first authors increased from 14.60% in 2000 to 45.0% in 2020 (P < .001). The percentage of women senior authors increased from 5.60% in 2000 to 18.80% in 2020 (P < .001). Women first authors were more likely to perform research with women senior authors (18.42%) than with men senior authors (10.23%, P < .001). The proportion of women first authors from Oceania were higher than that from North and South America (P = .004), whereas there was no statistical difference regarding women senior authors. In the past 2 decades, although the percentage of women authors among both first and senior authors in the field of H. pylori research has increased significantly, women are still a minority in original research.

Application of a Machine Learning Predictive Model for Recurrent Acute Pancreatitis.

BACKGROUND AND AIM: Acute pancreatitis is the main cause of hospitalization for pancreatic disease. Some patients tend to have recurrent episodes after experiencing an episode of acute pancreatitis. This study aimed to construct predictive models for recurrent acute pancreatitis (RAP). METHODS: A total of 531 patients who were hospitalized for the first episode of acute pancreatitis at the Affiliated Hospital of Southwest Medical University from January 2018 to December 2019 were enrolled in the study. We confirmed whether the patients had a second episode until December 31, 2021, through an electronic medical record system and telephone or WeChat follow-up. Clinical and follow-up data of patients were collected and randomly allocated to the training and test sets at a ratio of 7:3. The training set was used to select the best model, and the selected model was tested with the test set. The area under the receiver operating characteristic curves, sensitivity, specificity, positive predictive value, negative predictive value, accuracy, decision curve, and calibration plots were used to assess the efficacy of the models. Shapley additive explanation values were used to explain the model. RESULTS: Considering multiple indices, XGBoost was the best model. The area under the receiver operating characteristic curves, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model in the test set were 0.779, 0.763, 0.883, 0.647, 0.341, and 0.922, respectively. According to the Shapley additive explanation values, drinking, smoking, higher levels of triglyceride, and the occurrence of ANC are associated with RAP. CONCLUSION: The XGBoost model shows good performance in predicting RAP, which may help identify high-risk patients.

IGF2/IGF2R/Sting signaling as a therapeutic target in DSS-induced ulcerative colitis.

Ulcerative colitis is an inflammatory bowel disease with increasing prevalence and incidence. Current treatments for ulcerative colitis are not generally applicative and are often accompanied by side effects. IGF2 is an endogenous protein that plays roles in anti-inflammation and stemness maintenance, but little is known about its mechanism and function in the progression of ulcerative colitis. In this study, mouse recombinant IGF2 was used in a mouse model of ulcerative colitis established by DSS. IGF2 expression was reduced in colon tissues but not plasma of DSS-induced colitis mice. IGF2R expression was also decreased in colitis colons, which was then elevated by recombinant IGF2. Recombinant IGF2 alleviated colon injury in colitis, which was evaluated by colon shortening, body weight loss and DAI score. IGF2 treatment also relieved the inflammatory response in colitis, which was assessed by the spleen weight index, MPO activity and proinflammatory cytokine expression and was also detected in LPS-stimulated RAW264.7 cells in vitro. Moreover, IGF2R was predicted and further verified to interact with the Sting protein, and the cGAS-Sting pathway as a key pathway for stemness regulation, was upregulated in colonic colons, which was blocked by IGF2 treatment. Additionally, IGF2 treatment can maintain colonic stemness and further repair colonic tight junction function in DSS-induced colitis. In conclusion, IGF2/IGF2R downregulated the cGAS-Sting pathway to sustain colonic stemness and barrier integrity to protect against ulcerative colitis induced by DSS.

FANCD2 as a novel prognostic biomarker correlated with immune and drug therapy in Hepatitis B-related hepatocellular carcinoma.

BACKGROUND: Ferroptosis is related to the immunosuppression of tumors and plays a critical role in cancer progression. Fanconi anemia complementation group D2 (FANCD2) is a vital gene that regulates ferroptosis. However, the mechanism of action of FANCD2 in Hepatitis B-related hepatocellular carcinoma (HCC) remains unknown. In this study, we investigated the prognostic significance and mechanism of action of FANCD2 in Hepatitis B-related HCC. METHODS: The expression of FANCD2 in Hepatitis B-related HCC was explored using The Cancer Genome Atlas (TCGA) and validated using the Gene Expression Omnibus (GEO) database. Univariate and multivariate Cox regression analyses and Kaplan-Meier survival curves were used to analyze the relationship between FANCD2 expression and the overall survival of patients with Hepatitis B-related HCC. Protein-protein interaction networks for FANCD2 were built using the STRING website. In addition, correlations between FANCD2 expression and the dryness index, tumor mutational burden, microsatellite instability (MSI), immune pathways, genes involved in iron metabolism, and sorafenib chemotherapeutic response were analyzed. RESULTS: Our results indicated that FANCD2 was significantly overexpressed in Hepatitis B-related HCC and demonstrated a strong predictive ability for diagnosis (Area Under Curve, 0.903) and prognosis of the disease. High FANCD2 expression was associated with poor prognosis, high-grade tumors, high expression of PDL-1, high MSI scores, and low sorafenib IC50 in Hepatitis B-related HCC. BRCA1, BRCA2, FAN1, and FANCC were vital proteins interacting with FANCD2. The expression level of FANCD2 significantly correlated with the infiltration levels of Treg cells, B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages, myeloid dendritic cells, and NK cells in Hepatitis B-related HCC. FANCD2 was positively correlated with the tumor proliferation signature pathway, DNA repair, and cellular response to hypoxia. CONCLUSION: Our study indicated that FANCD2 was a potential novel biomarker and immunotherapeutic target against Hepatitis B-related HCC, which might be related to the chemotherapeutic response to sorafenib.

Prediction of in-hospital Mortality of Intensive Care Unit Patients with Acute Pancreatitis Based on an Explainable Machine Learning Algorithm.

BACKGROUND AND AIM: Acute pancreatitis (AP) is potentially fatal. Therefore, early identification of patients at a high mortality risk and timely intervention are essential. This study aimed to establish an explainable machine-learning model for predicting in-hospital mortality of intensive care unit (ICU) patients with AP. METHODS: Data on patients with AP, including demographics, vital signs, laboratory tests, comorbidities, treatment, complication, and severity scores, were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU collaborative research database (eICU-CRD). Based on the data from MIMIC-IV, we used the least absolute shrinkage and selection operator algorithm to select variables and then established 9 machine-learning models and screened the optimal model. Data from the eICU-CRD were used for external validation. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, decision curve, and calibration plots were used to assess the models' efficacy. Shapley's additive explanation values were used to explain the model. RESULTS: Gaussian naive Bayes (GNB) model had the best performance on the data from MIMIC-IV, with an AUC, accuracy, sensitivity, and specificity of 0.840, 0.787, 0.839, and 0.792, respectively. The GNB model also performed well on the data from the eICU-CRD, with an AUC, accuracy, sensitivity, and specificity of 0.862, 0.833, 0.848, and 0.763, respectively. According to Shapley's additive explanation values, the top 4 predictive factors were maximum red cell distribution width, minimum saturation of blood oxygen, maximum blood urea nitrogen, and the Sequential Organ Failure Assessment score. CONCLUSION: The GNB model demonstrated excellent performance and generalizability in predicting mortality in ICU patients with AP. Therefore, it can identify patients at a high mortality risk.

Global burden of early-onset colorectal cancer among people aged 40-49 years from 1990 to 2019 and predictions to 2030.

PURPOSE: To explore the disease burden of early-onset colorectal cancer (EO-CRC) in individuals aged 40-49 years and provide baseline evidence for routine recommended age adjustment for CRC screening and other clinical decision-making. METHODS: We collected data stratified by sex, risk factors, and socio-demographic index (SDI) from the Global Burden of Disease Study 2019 Data Resources. Trends in disease burden were analyzed by estimated annual percentage change. The Bayesian age-period-cohort model predicted the burden over the following 10 years. RESULTS: In 2019, the global rates of incidence, mortality, prevalence, and disability-adjusted life year (DALY) of EO-CRC in people aged 40-44 years were 11.48 (95% uncertainty interval: 10.50-12.59), 4.35 (4.01-4.70), 72.63 (66.48-79.52), 209.82 (193.55-226.59) per 100,000 population. For people aged 45-49 years, the rates of these four estimates were 19.63 (17.97-21.54), 7.76 (7.16-8.41), 121.73 (110.99-133.84), and 335.83 (310.14-362.91), respectively. The incidence and prevalence rates for both age groups increased while the mortality and DALY rates remained stable from 1990 to 2019. In 2019, high-income North America had the highest incidence and prevalence rates. A low milk diet accounted for the largest proportion of global DALYs in EO-CRC, and there was a tendency for the DALY rate first to increase and then decrease with increasing SDI. The incidence and mortality rates were predicted to increase in the next 10 years. CONCLUSION: The current and future burden of EO-CRC among people aged 40-49 years is heavy. Substantial variation exists in disease burden across regions and countries. Urgent screening actions and policies are needed.

Is the pelvic incidence a determinant factor for kyphosis curve patterns of ankylosing spondylitis patients?

To investigate the influence of pelvic incidence (PI) on the kyphosis curve patterns and clinical outcomes in ankylosing spondylitis (AS) patients with thoracolumbar kyphosis and to construct a classification of AS according to the PI value for surgical decision-making. 107 AS patients underwent single-level lumbar pedicle subtraction osteotomy (PSO) and finished a minimal of 2-year follow-up. All patients were divided into three groups: low PI (PI ≤ 40°), moderate PI (40° < PI ≤ 60°), and high PI (PI > 60°). Standing lateral radiographs were taken to evaluate the location of kyphotic apex, thoracic kyphosis (TK), lumbar lordosis (LL), C7 sagittal vertical axis (SVA), spino-sacral angle (SSA), global kyphosis (GK), PI, sacral slope (SS), and pelvic tilt (PT). Visual Analogue Scale (VAS) score, Oswestry Disability Index (ODI) and Bath Ankylosing Spondylitis Functional Index (BASFI) were used to evaluate quality of life. Before surgery, a significant difference was shown in the average LL and the mean GK in high PI group was the largest among the three groups. Correction of SVA, GK and LL in high PI group was the smallest among the three group. No significant difference in clinical outcomes was found among the three groups before surgery and at the final follow-up. Regarding the preoperative sagittal profile, the kyphosis curve pattern of moderate PI group is similar to that of low PI group. For AS patients in these two groups, harmonious sagittal alignment can be restored by a single-level PSO. However, the sagittal imbalance is insufficiently realigned by a single-level PSO in a patient with high PI.

Astaxanthin attenuated cigarette smoke extract-induced apoptosis via decreasing oxidative DNA damage in airway epithelium.

Chronic obstructive pulmonary disease (COPD) is a lung inflammatory disease that is associated with environmental allergic component exposure. Cigarette smoke is an environmental toxicant that induces lung malfunction leading to various pulmonary diseases. Astaxanthin (AST) is a carotenoid that shows antioxidant and anti-inflammatory activities which might be a promising candidate for COPD therapy. In this study, we released that AST could attenuate cigarette smoke-induced DNA damage and apoptosis in vivo and in vitro. AST administration ameliorated cigarette smoke extract (CSE)-induced activation of Caspase-3 and apoptosis. Pretreated mice with AST significantly decrease CSE-induced DNA damage which shows lower nuclear γ-H2AX level. AST treatment also dramatically reduces the production of intracellular reactive oxygen species (ROS) by suppressing the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme 4 (NOX4) and dual oxidase 1 (DUOX1). Taken together, this study suggested that AST can decrease CSE-induced DNA damage and apoptosis by inhibiting NOX4/DUOX1 expression that promotes ROS generation. AST may be a potential protective agent against CSE-associated lung disease that is worth in-depth investigation.

Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes.

SARS-CoV-2 spike protein (S) is structurally dynamic and has been observed by cryo-EM to adopt a variety of prefusion conformations that can be categorized as locked, closed, and open. S-trimers adopting locked conformations are tightly packed featuring structural elements incompatible with RBD in the "up" position. For SARS-CoV-2 S, it has been shown that the locked conformations are transient under neutral pH. Probably because of their transience, locked conformations remain largely uncharacterized for SARS-CoV-1 S. In this study, we introduced x1, x2, and x3 disulfides into SARS-CoV-1 S. Some of these disulfides have been shown to preserve rare locked conformations when introduced to SARS-CoV-2 S. Introduction of these disulfides allowed us to image a variety of locked and other rare conformations for SARS-CoV-1 S by cryo-EM. We identified bound cofactors and structural features that are associated with SARS-CoV-1 S locked conformations. We compare newly determined structures with other available spike structures of SARS-related CoVs to identify conserved features and discuss their possible functions.

The emerging role of long noncoding RNA in depression and its implications in diagnostics and therapeutic responses.

Depression is one of the most common mental illnesses, affecting more than 350 million people worldwide. However, the occurrence of depression is a complex process involving genetic, physiological, psychological, and social factors, and the underlying mechanisms of its pathogenesis remain unclear. With advances in sequencing technology and epigenetic studies, increasing research evidence suggests that long noncoding RNAs (lncRNAs) play nonnegligible roles in the development of depression and may be involved in the pathogenesis of depression through multiple pathways, including regulating neurotrophic factors and other growth factors and affecting synaptic function. In addition, significant alterations in lncRNA expression profiles in peripheral blood and different brain regions of patients and model animals with depression suggest that lncRNAs may function as biomarkers for the differential diagnosis of depression and other psychiatric disorders and may also be potential therapeutic targets. In this paper, the biological functions of lncRNAs are briefly described, and the functional roles and abnormal expression of lncRNAs in the development, diagnosis and treatment of depression are reviewed.