Hyaluronic acid-poly(glyceryl)10-stearate nanoemulsion for co-delivery of fish oil and resveratrol: Enhancing bioaccessibility and antioxidant potency.

Hyaluronic acid (HA), an endogenous polysaccharide comprising alternating D-glucuronic acid and N-acetylglucosamine units, is renowned for its high hydrophilicity, biocompatibility, and biodegradability. These attributes have rendered HA invaluable across medical and drug delivery fields. HA can be altered through physical, chemical, or enzymatic methods to improve the properties of the modified substances. In this work, we synthesized a derivative via the esterification of HA with poly(glyceryl)10-stearate (PG10-C18), designated as HA-PG10-C18. This novel derivative was employed to fabricate a nano co-delivery system (HA-PG10-C18@Res-NE) for fish oil and resveratrol (Res), aiming to enhance their stability and bioaccessibility. An exhaustive investigation of HA-PG10-C18@Res-NE revealed that the HA-modified system displayed superior physicochemical stability, notably in withstanding oxidation and neutralizing free radicals. Moreover, in vitro simulated digestion underscored the system's enhanced bioaccessibility of Res and more efficient release of free fatty acids. These outcomes underscore the strategic advantage of HA in modifying PG10-C18 for nanoemulsion formulation. Consequently, HA-PG10-C18 stands as a promising emulsifier for encapsulating lipophilic bioactives in functional foods, nutraceuticals, and pharmaceuticals.

Laboratory Experiments of Hydrocarbon Gas Flooding and Its Influencing Factors on Oil Recovery in a Low Permeability Reservoir with Medium Viscous Oil.

In view of the problems of low liquid production, a high proportion of high water cut wells, and poor development effect in the late stage of water flooding in the special sandstone reservoir of Niuquanhu "low permeability and medium viscosity crude oil", we carried out the research on hydrocarbon gas oil recovery and its influencing factors. First, the influence of different injected gas media on the physical properties of crude oil was analyzed. Second, the core displacement experiments of different gas injection media including CO2, CH4, and hydrocarbon gas were carried out by using the method of oil recovery comparison and optimization. Third, the indoor experimental study on the oil recovery of different influencing factors was carried out by using the method of controlling variables of influencing factors. Finally, the influence degree of different influencing factors on oil recovery was analyzed by a Spearman rank correlation coefficient analysis. The experimental results showed that the oil recovery of hydrocarbon gas is higher than that of CO2 and CH4, which were 57, 51, and 18% respectively. This is mainly because hydrocarbon gas is similar to the components of crude oil and is more easily dissolved in crude oil. The experimental results of influencing factors showed that the higher the content of C2-C4, the higher the oil recovery, and the content of C2-C4 will affect its dissolution with crude oil and its interaction with heavy component crude oil. The larger the permeability ratio, the lower the oil recovery, which was mainly due to the uneven distribution of injected gas in different regions. The higher the permeability, the lower the oil recovery, which was also due to the serious heterogeneity of the low permeability core of Niuquanhu; The results of Spearman rank correlation coefficient analysis based on different influencing factors and oil recovery showed that the order of influence of different factors on oil recovery was C2-C4 content > permeability ratio > permeability > back pressure > gas injection rate. In the development process of hydrocarbon gas injection, we should control the C2-C4 content, back pressure, and injection rate. The research in this study not only provides theoretical support for gas injection enhanced oil recovery technology in "low permeability and medium viscosity crude oil" reservoirs but also provides a new idea for the ranking of influencing factors.

A study on the bio-based surfactant sodium cocoyl alaninate as a foaming agent for enhanced oil recovery in high-salt oil reservoirs.

Environmental awareness is receiving increasing attention in the petroleum industry, especially when associated with chemical agents applied in enhanced oil recovery (EOR) technology. The bio-based surfactant sodium cocoyl alaninate (SCA) is environmentally friendly and can be easily biodegraded, which makes it a promising alternative to traditional surfactants. Herein, the SCA surfactant is proposed as a foaming agent for enhanced oil recovery. Laboratory investigations on the surfactant concentration, foaming performance, microbubble characterization, interfacial tension, and foam-flooding of the traditional surfactants SDS and OP-10 have been conducted. In particular, the anti-salt abilities of these three surfactants have been studied, taking into consideration the reservoir conditions at Bohai Bay Basin, China. The results show that concentrations of 0.20 wt%, 0.20 wt% and 0.50 wt% for SCA, SDS and OP-10, respectively, can achieve optimum foaming ability and foaming stability under formation salinity conditions, and 0.20 wt% SCA achieved the best foaming ability and stability compared to 0.20 wt% SDS and 0.50 wt% OP-10. Sodium fatty acid groups and amino acid groups present in the SCA molecular structure have high surface activities under different salinity conditions, making SCA an excellent anti-salt surfactant for enhanced oil recovery. The microstructure analysis results showed that most of the SCA bubbles were smaller in size, with an average diameter of about 150 µm, and the distribution of SCA bubbles was more uniform, which can reduce the risk of foam coalescence and breakdown. The IFT value of the SCA/oil system was measured to be 0.157 mN m-1 at 101.5 °C, which was the lowest. A lower IFT can make liquid molecules more evenly distributed on the surface, and enhance the elasticity of the foam film. Core-flooding experimental results showed that a 0.30 PV SCA foam and secondary waterflooding can enhance oil recovery by more than 15% after primary waterflooding, which can reduce the mobility ratio from 3.7711 to 1.0211. The more viscous SCA foam caused a greater flow resistance, and effectively reduced the successive water fingering, leading to a more stable driving process to fully displace the remaining oil within the porous media. The bio-based surfactant SCA proposed in this paper has the potential for application in enhanced oil recovery in similar high-salt oil reservoirs.

Improved physicochemical stability of fish oil nanoemulsion via a dense interfacial layer formed by hyaluronic acid-poly(glyceryl)10-stearate.

This study aimed to synthesize a novel emulsifier, hyaluronic acid-poly(glyceryl)10-stearate (HA-PG10-C18), and employ it for the fabrication of nanoemulsions incorporating deep-sea fish oil to improve their apparent solubility and physicochemical stability. 1H NMR and FT-IR analyses indicated successful synthesis of HA-PG10-C18. Nanoemulsions of deep-sea fish oil loaded with HA-PG10-C18 (HA-PG10-C18@NE) were successfully fabricated by ultrasonic emulsification. The fixed aqueous layer thickness (FALT) of PG10-C18@NE and HA-PG10-C18@NE was determined and the FALT of both nanoemulsions was similar, while the surface density of HA-PG10-C18@NE (4.92 × 10-12 ng/nm2) is 60 % higher than that of PG10-C18@NE (3.07 × 10-12 ng/nm2). Notably, HA-PG10-C18@NE demonstrated an exceptional physicochemical stability when exposed to various stressed environmental conditions, especially its freeze-thaw stability. Moreover, after simulated in vitro digestion, the HA-PG10-C18@NE exhibited a comparatively greater liberation of free fatty acids (94.0 ± 1.7 %) when compared to the release observed in PG10-C18@NE (85.5 ± 2.2 %).

A concise review of the regulatory, diagnostic, and prognostic implications of HOXB-AS3 in tumors.

Recent studies have reported that HOXB-AS3 (HOXB Cluster Antisense RNA 3) is an intriguing molecule with dual functionality as a long noncoding RNA (lncRNA) and putative coding peptide in tumorigenesis and progression. The significant expression alterations of HOXB-AS3 were detected in diverse cancer types and closely correlated with clinical stage and patient survival. Furthermore, HOXB-AS3 was involved in a spectrum of biological processes in solid tumors and hematological malignancies, such as stemness, lipid metabolism, migration, invasion, and tumor growth. This review comprehensively analyzes its clinical relevance for diagnosis and prognosis across human tumors and summarizes its functional role and regulatory mechanisms in different malignant tumors, including liver cancer, acute myeloid leukemia, ovarian cancer, lung cancer, endometrial carcinoma, colon cancer, and oral squamous cell carcinoma. Overall, HOXB-AS3 emerges as a promising biomarker and novel therapeutic target in multiple human tumors.

Association of clinical characteristics and vaccines with risk of persistently viral clearance in patients infected with SARS-CoV-2 Omicron variant in Shanghai, China.

Importance: The global COVID-19 pandemic does not appear to end in the near future. Currently, limited data are available on the risk factors for delayed viral clearance in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection. Objective: This study aimed to investigate the association of clinical characteristics and vaccination with prolonged viral clearance. Methods: This retrospective cohort included 16,985 patients who had contracted the SARS-CoV-2 Omicron variant between April 5 and May 30, 2022, in Shanghai, China, and had mild or no symptoms. The patients were admitted to the quarantine venue at the Shanghai New International Expo Center. Results: Of the 16,985 participants, the occurrence of viral clearance was ≤8 and > 8 days in 11,009 (64.8 %) and 5976 (35.2 %) participants, respectively. Risk factors related to patients who remained persistently polymerase chain reaction (PCR)-positive were sex (Male, odds ratio [OR] 1.221, p < 0.001), older age (35-49, OR 1.389, p < 0.001; 50-64, OR 1.659, p < 0.001; ≥65, OR 2.139, p < 0.001), presence of symptoms (OR 1.093, p = 0.030), number of vaccinations (two doses, OR 0.753, p < 0.001; three doses, OR 0.797, p < 0.001; four doses, OR 0.543, p < 0.001), and cycle threshold (Ct) value for ORF1ab gene at diagnosis (25-35, OR 0.235, p < 0.001; >35, OR 0.079, p < 0.001). The lower rates of increase in Ct values were observed in the later viral shedding group than in the early viral shedding group for ORF1ab (ß = -0.791, p < 0.001) and N genes (ß = -0.825, p < 0.001). Conclusion: Prolonged SARS-CoV-2 RNA detection and higher viral concentrations were associated with factors such as male sex, older age, symptomatic status, and fewer doses of vaccination in patients admitted to Shanghai Makeshift Hospital between April 5 and May 30, 2022.

Prognostic value of normal levels of preoperative tumor markers in colorectal cancer.

Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), and alpha-fetoprotein (AFP) are widely used tumor markers for colorectal cancer (CRC), but their clinical significance is unknown when the levels of these tumor markers were within the normal range. This retrospective study included 2145 CRC patients. The entire cohort was randomly divided into training and validation datasets. The optimal cut-off values of tumor markers were calculated using X-tile software, and univariate and multivariate analyses were performed to assess its association with overall survival (OS). The nomogram model was constructed and validated. The entire cohort was randomly divided into a training dataset (1502 cases, 70%) and a validation dataset (643 cases,30%). Calculated from the training dataset, the optimal cut-off value was 2.9 ng/mL for CEA, 10.1 ng/mL for CA19-9, 13.4 U/mL for CA125, and 1.8 ng/mL for AFP, respectively. Multivariate analysis revealed that age, tumor location, T stage, N stage, preoperative CA19-9, and CA125 levels were independent prognostic predictors. Even within the normal range, CRC patients with relatively high levels of CA19-9 or CA125 worse OS compared to those with relatively low levels. Then, based on the independent prognostic predictors from multivariate analysis, two models with/without (model I/II) CA19-9 and CA125 were built, model I showed better prediction and reliability than model II. Within the normal range, relatively high levels of preoperative CA19-9 and CA125 were significantly associated with poor OS in CRC patients. The nomogram based on CA19-9 and CA125 levels showed improved predictive accuracy ability for CRC.

Single-cell analysis unveils activation of mast cells in colorectal cancer microenvironment.

The role of mast cells (MCs) in colorectal cancer (CRC) remains unclear, and a comprehensive single-cell study on CRC MCs has not been conducted. This study used a multi-omics approach, integrating single-cell sequencing, spatial transcriptomics, and bulk tissue sequencing data to investigate the heterogeneity and impact of MCs in CRC. Five MC signature genes (TPSAB1, TPSB2, CPA3, HPGDS, and MS4A2) were identified, and their average expression was used as a marker of MCs. The MC density was found to be lower in CRC compared to normal tissue, but MCs in CRC demonstrated distinct activation features. Activated MCs were defined by high expression of receptors and MC mediators, while resting MCs had low expression. Most genes, including the five MC signature genes, were expressed at higher levels in activated MCs. The MC signature was linked to a better prognosis in both CRC and pan-cancer patient cohorts. Elevated KITLG expression was observed in fibroblasts and endothelial cells in CRC samples compared to normal tissue, and co-localization of MCs with these cell types was revealed by spatial transcriptome analysis. In conclusion, this study finds decreased MC density in CRC compared to normal tissue, but highlights a shift in MC phenotype from CMA1high resting cells to activated TPSAB1high, CPA3high, and KIThigh cells. The elevated KITLG expression in the tumor microenvironment's fibroblasts and endothelial cells may activate MCs through the KITLG-KIT axis, potentially suppressing tumor progression.

A nomogram was developed using clinicopathological features to predict postoperative liver metastasis in patients with colorectal cancer.

PURPOSE: The objective of this study is to examine the risk factors that contribute to the development of liver metastasis (LM) in patients who have suffered radical resection for colorectal cancer (CRC), and to establish a nomogram model that can be used to predict the occurrence of the LM. METHODS: The present study enrolled 1377 patients diagnosed with CRC between January 2010 and July 2021. The datasets were allocated to training (n = 965) and validation (n = 412) sets in a randomly stratified manner. The study utilized univariate and multivariate logistic regression analyses to establish a nomogram for predicting LM in patients with CRC. RESULTS: Multivariate analysis revealed that T stage, N stage, number of harvested lymph nodes (LNH), mismatch repair (MMR) status, neutrophil count, monocyte count, postoperative carcinoembryonic antigen (CEA) levels, postoperative cancer antigen 125 (CA125) levels, and postoperative carbohydrate antigen 19-9 (CA19-9) levels were independent predictive factors for LM after radical resection. These factors were then utilized to construct a comprehensive nomogram for predicting LM. The nomogram demonstrated great discrimination, with an area under the curve (AUC) of 0.782 for the training set and 0.768 for the validation set. Additionally, the nomogram exhibited excellent calibration and significant clinical benefit as confirmed by the calibration curves and the decision curve analysis, respectively. CONCLUSION: This nomogram has the potential to support clinicians in identifying high-risk patients who may develop LM post-surgery. Clinicians can devise personalized treatment and follow-up plans, ultimately leading to an improved prognosis for patients.

A retrospective study of Reyanning mixture in elderly patients infected with SARS-CoV-2 Omicron variant.

Objective: Reyanning mixture has been demonstrated to be effective in treating infected patients during the outbreak pandemic of SARS-CoV-2 Omicron variant of Coronavirus disease 2019 (COVID-19) in Shanghai 2022. The aim of this study is to further investigate the role of Reyanning mixture specifically in the treatment of elderly patients. Methods: This study enrolled 1,102 elderly patients who were infected with SARS-CoV-2 Omicron variant. Of these, 291 patients received Reyanning mixture in conjunction with conventional Western medicine treatment were assigned to the treatment group, while 811 patients only received conventional Western medicine treatment were assigned to the control group. Clinical parameters including hospitalization duration, viral shedding time, and Cycle Threshold (Ct) values of novel coronavirus nucleic acid tests, as well as adverse events were recorded and analyzed in both groups. Results: There was no significant difference in baseline characteristics between two groups. In comparison to the control group, the treatment group demonstrated a substantial difference in hospitalization duration (median: 8 days vs. 10 days, HR: 0.638, 95% CI: 0.558-0.731, p < 0.001). The treatment group also showed a significantly shorter viral shedding time compared to the control group (median: 7 days vs. 8 days, HR: 0.754, 95% CI: 0.659-0.863, p < 0.001). Multivariate Cox proportional-hazards model analysis indicated that the use of Reyanning mixture was closely associated with a reduction in hospitalization duration (HR: 1.562, 95% CI: 1.364-1.789, p < 0.001) and viral shedding time (HR: 1.335, 95% CI: 1.166-1.528, p < 0.001). In addition, during the treatment process, no serious adverse event occurred in either group. Conclusion: The improvement of clinical parameters in the treatment group indicate a promising therapeutic benefit of Reyanning mixture for elderly patients infected with SARS-CoV-2 Omicron variant in the present study. Further investigations are required to validate this finding by examining the underlying mechanism and function of Reyanning mixture.

Hyaluronic Acid Poly(glyceryl)10-Stearate Derivatives: Novel Emulsifiers for Improving the Gastrointestinal Stability and Bioaccessibility of Coenzyme Q10 Nanoemulsions.

Fish oils are a rich source of polyunsaturated fatty acids, including eicosapentaenoic acid and docosahexaenoic acid, which are reported to exhibit therapeutic effects in a variety of human diseases. However, these oils are highly susceptible to degradation due to oxidation, leading to rancidity and the formation of potentially toxic reaction products. The aim of this study was to synthesize a novel emulsifier (HA-PG10-C18) by esterifying hyaluronic acid with poly(glyceryl)10-stearate (PG10-C18). This emulsifier was then used to formulate nanoemulsion-based delivery systems to co-deliver fish oil and coenzyme Q10 (Q10). Q10-loaded fish oil-in-water nanoemulsions were fabricated, and then their physicochemical properties, digestibility, and bioaccessibility were measured. The results indicated that the environmental stability and antioxidant activity of oil droplets coated with HA-PG10-C18 surpassed those coated with PG10-C18 due to the formation of a denser interfacial layer that blocked metal ions, oxygen, and lipase. Meanwhile, the lipid digestibility and Q10 bioaccessibility of nanoemulsions formulated with HA-PG10-C18 (94.9 and 69.2%) were higher than those formulated with PG10-C18 (86.2 and 57.8%), respectively. These results demonstrated that the novel emulsifier synthesized in this study could be used to protect chemically labile fat-soluble substances from oxidative damage, while still retaining their nutritional value.

Reyanning Mixture on Asymptomatic or Mild SARS-CoV-2 Infection in Children and Adolescents: A Randomized Controlled Trial.

OBJECTIVE: To assess the effect and safety of Reyanning Mixture (RYN) in treating asymptomatic or mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents. METHODS: This is a prospective, open-label, randomized controlled trial. Patients aged 1-17 years and diagnosed with asymptomatic or mild coronavirus disease-2019 (COVID-19) were assigned to an intervention group (RYN plus standard care) and a control group (standard care) according to a randomization list. The primary outcomes were SARS-CoV-2 negative conversion time. Secondary outcomes included negative conversion rate on days 3 and 7, hospital length of stay, symptom relief rate, new-onset symptoms of asymptomatic infected patients, and progressive disease rate. The cycle threshold (Ct) values of ORF1ab or N genes were also tested. RESULTS: A total of 214 patients in the intervention group and 217 in the control group were analyzed. The SARS-CoV-2 negative conversion time was significantly shortened in the intervention group [5 days (interquartile range (IQR): 5-6) vs. 7 days (IQR: 6-7), P<0.01]. By days 3 and 7, the negative conversion rates were significantly higher in the intervention group (day 3: 32.7% vs. 21.2%, P=0.007; day 7: 75.2% vs. 60.8%, P=0.001). Ct values significantly increase on day 2 [ORF1ab gene: 35.62 (IQR: 29.17-45.00) vs. 34.22 (IQR: 28.41-39.41), P=0.03; N gene: 34.97 (IQR: 28.50-45.00) vs. 33.51 (IQR: 27.70-38.25), P=0.024] and day 3 [ORF1ab gene: 38.00 (IQR: 32.72-45.00) vs. 35.81 (IQR: 29.96-45.00), P=0.003; N gene: 37.16 (IQR: 32.01-45.00) vs. 35.26 (IQR: 29.09-45.00), P=0.01]. No significant difference was found in hospital length of stay between the two groups (P>0.05). Symptoms of cough were significantly improved (82.2% vs. 70.0%, P=0.02) and wheezing was significantly reduced (0.7% vs. 12.9%, P<0.01) in the intervention group compared with the control group. During the trial, no disease progression or serious adverse events were reported. CONCLUSION: Adding RYN to standard care may be a safe and effective treatment for children with asymptomatic and mild SARS-CoV-2 infection. (Registration No. ChiCTR2200060292).

Efficacy of Lianhua Qingwen for children with SARS-CoV-2 Omicron infection: A propensity score-matched retrospective cohort study.

BACKGROUND: Lianhua Qingwen Granules or Capsules (LHQW) has accumulated much research evidence in the fight against the coronavirus disease 2019 (COVID-19) epidemic. However, there are still few data on its efficacy and safety in children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. PURPOSE: To evaluate the efficacy and safety of LHQW in children with SARS-CoV-2 Omicron infection. METHODS: We conducted a single-center, propensity-score matched retrospective cohort study of children with SARS-CoV-2 Omicron infection in Shanghai New International Expo Center mobile cabin hospital between April 1st and June 1st, 2022. Eligible patients received either LHQW granules/capsules plus supportive care (LHQW group) or supportive care alone (control group). The primary outcome was the negative conversion time of nucleic acid. Secondary outcomes included the negative conversion rate of nucleic acid, the length of hospital stay, clinical disease progression, and cycle threshold [Ct] values for SARS-CoV-2 open reading frame [ORF1ab] or nucleocapsid [N] genes. RESULTS: Overall, 2808 patients were enrolled, and 346 patients in each group were included in the analysis. Among the propensity-score matched groups, LHQW treatment was associated with an accelerated negative conversion time of nucleic acid (median: 5 d vs. 6 d, Hazard ratio: 1.25, 95% CI: 1.08 - 1.46, Log-rank p < 0.001), a higher negative conversion rate of nucleic acid (Day 2 - 6: 2.9% vs. 0.6%, p = 0.036; 29.8% vs. 5.5%, p < 0.001; 42.5% vs. 24.3%, p < 0.001; 51.4% vs. 31.5%, p < 0.001; 63.3% vs. 55.2%, p = 0.030), shorter hospital stay (median: 10 d vs. 11 d, Hazard ratio: 1.50, 95% CI: 1.29 - 1.74, Log-rank p < 0.001), and lower rates of asymptomatic infection progressing to mild (37.9% vs. 46.5%, p = 0.021). CONCLUSION: Our study suggested that LHQW treatment was associated with faster clinical recovery in children with SARS-CoV-2 Omicron infection.

Efficacy and safety of Reyanning mixture in patients infected with SARS-CoV-2 Omicron variant: A prospective, open-label, randomized controlled trial.

BACKGROUND: A wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant rapidly resulted in a steep increase in the infected population and an overloaded healthcare system. Effective medications for Omicron are currently limited. The previous observational study supports the efficacy and safety of Reyanning (RYN) mixture in the treatment of coronavirus disease 2019 (COVID-19). PURPOSE: To evaluate the efficacy of RYN in asymptomatic and mildly infected patients with SARS-CoV-2 infection. STUDY DESIGN AND METHODS: This study was a prospective, open-label, randomized controlled trial. We consecutively recruited 2830 patients from Shanghai New International Expo Center mobile cabin hospital and randomized them in a 1:1 ratio to receive RYN plus standard care or receive standard care alone. The primary outcomes were the negative conversion of nucleic acid. Secondary outcomes included the hospital duration, new-onset symptoms, proportion of disease progression, and the viral load measured by the cycle threshold (Ct) value. RESULTS: A total of 1393 patients in the intervention group and 1407 patients in the control group completed the study. The negative conversion time of nucleic acid was significantly shortened in the intervention group (median: 6 d vs. 7 d, Hazard ratio: 0.768, 95CI %: 0.713-0.828, p < 0.0001). The negative conversion rate of nucleic acid was significantly higher in the intervention group (Day 3: 32.4% vs. 18.3%; Day7: 65.3% vs. 55.2%, p < 0.001). The hospitalization duration was significantly shortened in the intervention group (median: 8 d vs. 9 d, Hazard ratio: 0.759, 95% CI: 0.704-0.818, p < 0.0001). The proportion of new-onset fever (2.4% vs. 4.1%, p = 0.012), coughing (12.2% vs. 14.8%, p = 0.046), and expectoration (6.0% vs. 8.0%, p = 0.032) in the intervention group was significantly lower. RYN treatment increased Ct values and reduced the viral load. No disease progression and serious adverse events were reported during the study. CONCLUSION: RYN is a safe and effective treatment that can accelerate virus clearance and promote disease recovery in asymptomatic and mild Omicron infections.

Immunomodulatory effects of atorvastatin on MRL/lpr mice.

BACKGROUND: Statins have long been extensively prescribed as effective lipid-lowering agents, but statins have also been recognized as novel immunomodulators in recent years. This study was designed to investigate the immunomodulatory effects of atorvastatin on lupus-prone MRL/lpr mice. METHODS: A total of 30 8-week-old female MRL/lpr mice were randomly divided into three groups and orally administered vehicle, atorvastatin orhydroxychloroquine sulfate for 11 weeks. In vivo, the effects of atorvastatin on the survival rate, renal function and spleen index in MRL/lpr mice were examined. Ex vivo, splenic B-cell proliferation was assessed by a Cell Counting Kit-8. RESULTS: Oral atorvastatin failed to prolong survival time, or reduce the levels of proteinuria, or serum anti-dsDNA antibody and complement proteins (C3, C4). Histologically, no significant improvement by atorvastatin was observed in the pathological manifestations of renal damage, while hydroxychloroquine sulfate significantly improved glomerular injury. Ex vivo, atorvastatin suppressed the proliferation of splenic B lymphocytes. CONCLUSION: Oral atorvastatin monotherapy had no therapeutic effects on MRL/lpr mice, whereas atorvastatin inhibited splenic B-cell proliferation in vitro, suggesting that atorvastatin has a potential therapeutic effect on systemic lupus erythematosus.

Analysis of Prognostic Factors of Rectal Cancer and Construction of a Prognostic Prediction Model Based on Bayesian Network.

Background: The existing prognostic models of rectal cancer after radical resection ignored the relationships among prognostic factors and their mutual effects on prognosis. Thus, a new modeling method is required to remedy this defect. The present study aimed to construct a new prognostic prediction model based on the Bayesian network (BN), a machine learning tool for data mining, clinical decision-making, and prognostic prediction. Methods: From January 2015 to December 2017, the clinical data of 705 patients with rectal cancer who underwent radical resection were analyzed. The entire cohort was divided into training and testing datasets. A new prognostic prediction model based on BN was constructed and compared with a nomogram. Results: A univariate analysis showed that age, Carcinoembryonic antigen (CEA), Carbohydrate antigen19-9 (CA19-9), Carbohydrate antigen 125 (CA125), preoperative chemotherapy, macropathology type, tumor size, differentiation status, T stage, N stage, vascular invasion, KRAS mutation, and postoperative chemotherapy were associated with overall survival (OS) of the training dataset. Based on the above-mentioned variables, a 3-year OS prognostic prediction BN model of the training dataset was constructed using the Tree Augmented Naïve Bayes method. In addition, age, CEA, CA19-9, CA125, differentiation status, T stage, N stage, KRAS mutation, and postoperative chemotherapy were identified as independent prognostic factors of the training dataset through multivariate Cox regression and were used to construct a nomogram. Then, based on the testing dataset, the two models were evaluated using the receiver operating characteristic (ROC) curve. The results showed that the area under the curve (AUC) of ROC of the BN model and nomogram was 80.11 and 74.23%, respectively. Conclusion: The present study established a BN model for prognostic prediction of rectal cancer for the first time, which was demonstrated to be more accurate than a nomogram.