Machine learning-based models for advanced fibrosis and cirrhosis diagnosis in chronic hepatitis B patients with hepatic steatosis.

BACKGROUND AND AIMS: The global rise of chronic hepatitis B (CHB) superimposed on hepatic steatosis (HS) warrants non-invasive, precise tools for assessing fibrosis progression. This study leveraged machine learning (ML) to develop diagnostic models for advanced fibrosis and cirrhosis in this patient population. METHODS: Treatment-naive CHB patients with concurrent HS who underwent liver biopsy in ten medical centers were enrolled as a training cohort and an independent external validation cohort (NCT05766449). Six ML models were implemented to predict advanced fibrosis and cirrhosis. The final models, derived from Shapley Additive exPlanations, were compared to Fibrosis-4 Index (FIB-4), Nonalcoholic fatty liver disease Fibrosis Score (NFS), and Aspartate transaminase to platelet ratio index (APRI) using the area under receiver operating characteristic curve (AUROC), and decision curve analysis (DCA). RESULTS: Of 1,198 eligible patients, the random forest (RF) model achieved AUROCs of 0.778 [95% confidence interval (CI) 0.749-0.807] for diagnosing advanced fibrosis (RF-AF model) and 0.777 (95%CI 0.748-0.806) for diagnosing cirrhosis (RF-C model) in the training cohort, and maintained high AUROCs in the validation cohort. In the training cohort, the RF-AF model obtained an AUROC of 0.825 (95% CI 0.787-0.862) in patients with HBV DNA ≥105 IU/ml, and RF-C model had an AUROC of 0.828 (95% CI 0.774-0.883) in female patients. The two models outperformed FIB-4, NFS, and APRI in the training cohort, and also performed well in the validation cohort. CONCLUSION: The RF models provide reliable, non-invasive tools for identifying advanced fibrosis and cirrhosis in CHB patients with concurrent HS, offering a significant advancement in the co-management of the two diseases.

Antiviral therapy response in patients with chronic hepatitis B and fatty liver: A systematic review and meta-analysis.

The impact of concurrent fatty liver (FL) on response to antiviral therapy in chronic hepatitis B (CHB) patients has not been well characterized. We aimed to systematically review and analyse antiviral treatment response in CHB patients with and without FL. We searched PubMed, Embase, Web of Science and the Cochrane Library databases from inception to 31 May 2023 for relevant studies. Biochemical response (BR), complete viral suppression (CVS) and hepatitis B e antigen (HBeAg) seroconversion in CHB patients with FL (CHB-FL) and without FL (non-FL CHB) were compared. In an initial pool of 2101 citations, a total of 10 studies involving 2108 patients were included. After 12 weeks of treatment, CHB-FL patients as compared with non-FL CHB patients had lower BR rate (48.37% [108/227] vs. 72.98% [126/174], p = .04) but similar trend for CVS (36.86% [80/227] vs. 68.81% [114/174], p = .05) and similar rates of HBeAg seroconversion (6.59% [7/103] vs. 7.40% [7/110], p = .89). However, at week 48, there were no statistically significant differences between CHB-FL and non-FL CHB patients in any of the outcomes, including BR (60.03% [213/471] vs. 69.37% [314/717], p = .67), CVS (65.63% [459/746] vs. 73.81% [743/1132], p = .27) and HBeAg seroconversion (10.01% [30/275] vs. 14.06% [65/453], p = .58) with similar findings for week 96. BR rate was lower in CHB-FL patients after 12 weeks of antiviral treatment. However, after a longer follow-up of either 48 or 96 weeks, no statistically significant differences were observed in BR, CVS or HBeAg seroconversion rates between CHB patients with and without FL.

Different minimal alcohol consumption in male and female individuals with metabolic dysfunction-associated fatty liver disease.

BACKGROUND AND AIMS: The relationship between moderate alcohol intake and health outcomes among individuals with metabolic dysfunction-associated fatty liver disease (MAFLD) is complex. Our aim was to investigate the association of minimal alcohol consumption with all-cause and cause-specific mortality among MAFLD individuals of different genders. METHODS: Our study included 2630 MAFLD individuals from the Third National Health and Nutrition Examination Survey. Cox regression analysis was performed to assess the association between alcohol use measures and all-cause and cause-specific mortality. Restricted cubic spline curves were used to evaluate the relationship between alcohol consumption per week and all-cause mortality. RESULTS: In the entire MAFLD cohort, we observed significant disparities in clinical characteristics between male and female individuals with MAFLD. Higher weekly alcohol consumption was significantly associated with all-cause and cause-specific mortality (male, hazard ratios [HRs]: 1.009, 95% CIs: 1.004-1.014; female, HRs: 1.032, 95% CIs: 1.022-1.042). In males with MAFLD, a linear association with all-cause mortality was observed for weekly alcohol consumption (p for non-linearity = .21). Conversely, in females with MAFLD, the risk of all-cause mortality remained relatively stable until 2 drinks per week, after which it rapidly increased with each additional drink consumed, and the increase in mortality risk was higher than that observed in males (p for non-linearity < .05). CONCLUSIONS: Our findings indicate that any increase in weekly alcohol consumption was associated with increased all-cause mortality in men with MAFLD. Conversely, consuming less than 2 drinks per week had minimal impact on the risk of mortality among female.

α-Acyloxylation of Ketones/Cyclic Ethers Mediated by Hypervalent Iodine(III) Reagents as Oxidants and Nucleophilic Sources.

This study describes a catalyst-free α-acyloxylation of ketones and a KBr-mediated α-acyloxylation of cyclic ethers. These conversions are effectively mediated by hypervalent iodine(III) reagents serving dual roles as the oxidant and nucleophilic source. Consequently, esters are produced directly in moderate to excellent yields. The proposed method features good functional group compatibility, a broad substrate scope, and high synthetic efficiency and is remarkably environmentally friendly.

Dithienocoronene diimide (DTCDI)-derived triads for high-performance air-stable, solution-processed balanced ambipolar organic field-effect transistors.

Developing ambipolar organic semiconducting materials is essential for use in complementary-like inverters and light-emitting transistors. In this study, three new dithienocoronenediimide (DTCDI)-derived triads, DTCDI-BT, DTCDI-BBT and DTCDI-BNT, were designed and synthesized, in which various sizes of terminal groups, i.e., thiophene (T), benzo[b]thiophene (BT) and naphtha[2,3-b]thiophene (NT) were substituted at the α-positions of the two thiophene rings of DTCDI, respectively. The DFT calculations reveal that the HOMO energy levels of the three triads when compared to that of the parent DTCDI-core (-5.99 eV) are significantly increased to -5.59, -5.59 and -5.45 eV for DTCDI-BT, DTCDI-BBT and DTCDI-BNT, respectively, whereas the LUMO energy levels (-3.07 eV ∼ -3.14 eV) are almost identical with that of the DTCDI-core (-3.10 eV). The results predict that the triads could possess ambipolar transport properties in organic field-effect transistor (OFET) applications. In fact, under an ambient atmosphere, solution-processed bottom-gate top-contact (BGTC) transistors exhibit ambipolar charge transport properties by tuning the HOMOs of the DTCDI-based triads so that they were suitable for hole injection, resulting in balanced maximum electron and hole mobilities of 1.66 × 10-3 and 1.02 × 10-3 cm2 V-1 s-1 for DTCDI-BT, 2.60 × 10-2 and 3.60 × 10-2 cm2 V-1 s-1 for DTCDI-BBT, and 2.43 × 10-3 and 4.15 × 10-3 cm2 V-1 s-1 for DTCDI-BNT, respectively. This is the first time that the DTCDI building block has been used to develop ambipolar small molecular semiconductors, and achieved a device performance comparable to that of the DTCDI-based polymeric semiconductors. In addition, DTCDI-BBT-based complementary-like inverters were made, and the inverter devices operated well in both p-mode and n-mode under ambient conditions. The results show that the DTCDI is a promising π-electron-deficient building block which could be further used to develop ambipolar semiconducting materials for OFET devices.

Development of a ratiometric two-photon fluorescent probe for imaging of hydrogen peroxide in ischemic brain injury.

Hydrogen peroxide (H2O2) plays crucial roles in immunological processes and has been revealed to be closely linked to the hypoxic-ischemic process. Thus, it is important to develop a reliable method for monitoring H2O2 in hypoxic-ischemic brain injury (HIBI). To achieve this, we report on a rationally designed fluorene-based ratiometric two-photon fluorescent probe for H2O2, i.e., FH2O2. The probe and fluorophore were tested under either one- or two-photon modes, respectively. After reacting with H2O2, the relative emission intensity ratio at wavelengths of 390-465 (Fblue) and 500-550 nm (Fyellow) of FH2O2 had a 6.5-fold increase (Fyellow/Fblue) within 40 min, and the maximal two-photon active cross-section value was detected as 66 GM at a wavelength of 750 nm. The probe exhibited high selectivity, low cytotoxicity, high sensitivity with a detection limit of 0.57 µM, and adequate photostability. After confirming satisfactory sensing performance of the probe in vitro, we were able to monitor H2O2in situ in mice with HIBI via two-photon microscopy, which could provide a potential method for clinical diagnosis during the neonatal HIBI process.

[Empagliflozin inhibits inflammatory response and alleviates renal injury in type 2 diabetic rats by up-regulating the expression of exchange protein 1 directly activated by cAMP (Epac1)].

Objective To observe the therapeutic effect of empagliflozin (EM) on renal injury in rats with type 2 diabetes mellitus (T2DM), and to explore its possible mechanism. Methods Male SD rats were randomly divided into a normal control (NC) group, a T2DM group, and an EM group, with 6 rats in each group. T2DM models were established by an intraperitoneal injection of streptozotocin (STZ) in the T2DM and EM groups. Fasting blood glucose (FBG) levels and body mass of rats in each group were recorded. The EM group received EM solution through intragastric administration, while the other two groups were given an equivalent volume of sodium carboxymethyl cellulose solution through intragastric administration for 12 weeks. After the body mass and FBG levels were recorded, the rats were sacrificed and blood samples from the abdominal aorta and kidney tissues were collected. Serum creatinine (Scr), blood urea nitrogen (BUN), uric acid (UA), triglyceride (TG) and total cholesterol (TC) were detected by automatic biochemical analyzer. Masson, PAS and HE staining were used to assess histological changes in the kidneys, and a transmission electron microscopy was used to observe ultrastructural changes. Immunohistochemical staining was used to detect the expression and distribution of exchange protein 1 directly activated by cAMP(Epac1), TNF-α, IL-1ß, and IL-18 in renal tissue of rats. Results Compared with the NC group, the rats in T2DM group showed a decrease in body mass, a significant increase in the levels of FBG, Scr, BUN, UA, TC, and TG, thickened glomerular basement membrane, foot process fusion of podocytes, disordered cell arrangement and loss of endothelial cell fenestrations. The expression level of Epac1 decreased, while the expression levels of TNF-α, IL-1ß, and IL-18 significantly increased. Compared with the T2DM group, the rats in the EM group showed an increase in body mass, significantly decreased levels of FBG, Scr, BUN, UA, TC, and TG, reduced renal injury, increased expression level of Epac1, and significantly decreased expression levels of TNF-α, IL-1ß, and IL-18. Conclusion EM can improve renal injury in T2DM rats by up-regulating Epac1 expression to inhibit inflammatory response.

The impact of an increased Fibrosis-4 index and the severity of hepatic steatosis on mortality in individuals living with diabetes.

BACKGROUND AND AIMS: Data on the effects of liver fibrosis and hepatic steatosis on outcomes in individuals living with diabetes are limited. Therefore, we investigated the predictive value of the fibrosis and the severity of hepatic steatosis for all-cause mortality in individuals living with diabetes. METHODS: A total of 1903 patients with diabetes from the Third National Health and Nutrition Examination Survey (NHANES III) dataset were enrolled. Presumed hepatic fibrosis was evaluated with Fibrosis-4 index (FIB-4). The mortality risk and corresponding hazard ratio (HR) were analyzed with the Kaplan-Meier method and multivariable Cox proportional hazard models. RESULTS: Over a median follow-up of 19.4 years, all-cause deaths occurred in 69.6%. FIB-4 ≥ 1.3 was an independent predictor of mortality in individuals living with diabetes (HR 1.219, 95% confidence interval [CI]: 1.067-1.392, p = 0.004). Overall, FIB-4 ≥ 1.3 without moderate-severe steatosis increased the mortality risk (HR 1.365; 95%CI 1.147-1.623, p < 0.001). The similar results were found in individuals living with diabetes with metabolic dysfunction-associated fatty liver disease (MAFLD) (HR 1.499; 95%CI 1.065-2.110, p = 0.020), metabolic syndrome (MetS) (HR 1.397; 95%CI 1.086-1.796, p = 0.009) or abdominal obesity (HR 1.370; 95%CI 1.077-1.742, p = 0.010). CONCLUSIONS: Liver fibrosis, as estimated by FIB-4, may serve as a more reliable prognostic indicator for individuals living with diabetes than hepatic steatosis. Individuals living with diabetes with FIB-4 ≥ 1.3 without moderate-severe steatosis had a significantly increased all-cause mortality risk. These findings highlight the importance of identifying and monitoring those individuals, as they may benefit from further evaluation and risk stratification.

LiverRisk score: An accurate, cost-effective tool to predict fibrosis, liver-related, and diabetes-related mortality in the general population.

BACKGROUND: Noninvasive and early assessment of liver fibrosis is of great significance and is challenging. We aimed to evaluate the predictive performance and cost-effectiveness of the LiverRisk score for liver fibrosis and liver-related and diabetes-related mortality in the general population. METHODS: The general population from the NHANES 2017-March 2020, NHANES 1999-2018, and UK Biobank 2006-2010 were included in the cross-sectional cohort (n = 3,770), along with the NHANES follow-up cohort (n = 25,317) and the UK Biobank follow-up cohort (n = 17,259). The cost-effectiveness analysis was performed using TreeAge Pro software. Liver stiffness measurements ≥10 kPa were defined as compensated advanced chronic liver disease (cACLD). FINDINGS: Compared to conventional scores, the LiverRisk score had significantly better accuracy and calibration in predicting liver fibrosis, with an area under the receiver operating characteristic curve (AUC) of 0.76 (0.72-0.79) for cACLD. According to the updated thresholds of LiverRisk score (6 and 10), we reclassified the population into three groups: low, medium, and high risk. The AUCs of LiverRisk score for predicting liver-related and diabetes-related mortality at 5, 10, and 15 years were all above 0.8, with better performance than the Fibrosis-4 score. Furthermore, compared to the low-risk group, the medium-risk and high-risk groups in the two follow-up cohorts had a significantly higher risk of liver-related and diabetes-related mortality. Finally, the cost-effectiveness analysis showed that the incremental cost-effectiveness ratio for LiverRisk score compared to FIB-4 was USD $18,170 per additional quality-adjusted life-year (QALY) gained, below the willingness-to-pay threshold of $50,000/QALY. CONCLUSIONS: The LiverRisk score is an accurate, cost-effective tool to predict liver fibrosis and liver-related and diabetes-related mortality in the general population. FUNDING: The National Natural Science Foundation of China (nos. 82330060, 92059202, and 92359304); the Key Research and Development Program of Jiangsu Province (BE2023767a); the Fundamental Research Fund of Southeast University (3290002303A2); Changjiang Scholars Talent Cultivation Project of Zhongda Hospital of Southeast University (2023YJXYYRCPY03); and the Research Personnel Cultivation Program of Zhongda Hospital Southeast University (CZXM-GSP-RC125).

Development of a machine learning-based model to predict hepatic inflammation in chronic hepatitis B patients with concurrent hepatic steatosis: a cohort study.

Background: With increasingly prevalent coexistence of chronic hepatitis B (CHB) and hepatic steatosis (HS), simple, non-invasive diagnostic methods to accurately assess the severity of hepatic inflammation are needed. We aimed to build a machine learning (ML) based model to detect hepatic inflammation in patients with CHB and concurrent HS. Methods: We conducted a multicenter, retrospective cohort study in China. Treatment-naive CHB patients with biopsy-proven HS between April 2004 and September 2022 were included. The optimal features for model development were selected by SHapley Additive explanations, and an ML algorithm with the best accuracy to diagnose moderate to severe hepatic inflammation (Scheuer's system ≥ G3) was determined and assessed by decision curve analysis (DCA) and calibration curve. This study is registered with ClinicalTrials.gov (NCT05766449). Findings: From a pool of 1,787 treatment-naive patients with CHB and HS across eleven hospitals, 689 patients from nine of these hospitals were chosen for the development of the diagnostic model. The remaining two hospitals contributed to two independent external validation cohorts, comprising 509 patients in validation cohort 1 and 589 in validation cohort 2. Eleven features regarding inflammation, hepatic and metabolic functions were identified. The gradient boosting classifier (GBC) model showed the best performance in predicting moderate to severe hepatic inflammation, with an area under the receiver operating characteristic curve (AUROC) of 0.86 (95% CI 0.83-0.88) in the training cohort, and 0.89 (95% CI 0.86-0.92), 0.76 (95% CI 0.73-0.80) in the first and second external validation cohorts, respectively. A publicly accessible web tool was generated for the model. Interpretation: Using simple parameters, the GBC model predicted hepatic inflammation in CHB patients with concurrent HS. It holds promise for guiding clinical management and improving patient outcomes. Funding: This research was supported by the National Natural Science Foundation of China (No. 82170609, 81970545), Natural Science Foundation of Shandong Province (Major Project) (No. ZR2020KH006), Natural Science Foundation of Jiangsu Province (No.BK20231118), Tianjin Key Medical Discipline (Specialty), Construction Project, TJYXZDXK-059B, Tianjin Health Science and Technology Project key discipline special, TJWJ2022XK034, and Research project of Chinese traditional medicine and Chinese traditional medicine combined with Western medicine of Tianjin municipal health and Family Planning Commission (2021022).

A strategy for the treatment of gastrointestinal cancer: Targeting tumor senescent cells.

Gastrointestinal (GI) cancer includes a variety of cancers with high incidence that seriously threaten the lives of people worldwide. Although treatment strategies continue to improve, patient benefits are still very limited, and the ongoing search for new treatment strategies remains a priority. Cell senescence is closely related to the occurrence and development of tumors. For GI cancer, cell senescence may not only promote cancer but also bring new opportunities for treatment. Combined with relevant studies, we review the dual role of cell senescence in GI cancer, including the mechanism of inducing cell senescence, biomarkers of senescent cells, and potential of targeted senescence therapy for GI cancer.

Age-specific association between thyroid autoimmunity and hypothyroidism in Chinese adults aged over 65 years: a cross-sectional study.

Background: The correlation between thyroid autoimmune (TAI) disease and hypothyroidism in the elderly of different ages remains unclear. This study aimed to investigate the epidemiological characteristics of hypothyroidism, including subclinical hypothyroidism (Shypo) and overt hypothyroidism (Ohypo) in those aged ≥65 years from iodine-adequate areas and reveal the correlation between TAI and hypothyroidism in the elderly of different ages. Methods: It was a cross-sectional study involving 2,443 subjects aged ≥65 years from two iodine-adequate areas in China by cluster sampling. They were assigned to the 65-69-, 70-79-, and ≥80-year-old age group. All subjects were surveyed by questionnaires and received physical examinations, laboratory testing, and thyroid ultrasound. Epidemiological characteristics of thyroid diseases in the elderly were compared among the three groups. Risk factors for hypothyroidism were predicted by binary logistic regression analysis. Results: The median urinary iodine level was 238.70 (197.00, 273.70) µg/L. Thyroid peroxidase antibody or thyroglobulin antibody positivity (11.87%) and Shypo (9.13%) were common in the elderly. The prevalence of hypothyroidism in the elderly increases with age. TAI was a risk factor for Shypo (OR, 1.94; 95% CI, 1.35, 2.80; p < 0.01) and Ohypo (OR, 7.64; 95% CI, 3.40, 17.19; p < 0.01) in elderly Chinese. There was an age-specific correlation between TAI and hypothyroidism in the elderly. However, a significant correlation was not identified between TAI and hypothyroidism in ≥80-year-old age group (p > 0.05). Conclusion: Hypothyroidism, particularly Shypo, is common in the elderly from iodine-adequate areas in China. TAI serves as a risk factor for hypothyroidism in the elderly, with an age-specific correlation with hypothyroidism.

Prognostic Value of Venous Outflow Profiles on Multiphase CT Angiography for the Patients with Acute Ischemic Stroke After Endovascular Thrombectomy.

To evaluate the prognostic value of venous outflow (VO) profiles evaluated on multiphase CTA (mCTA) for the patients with acute ischemic stroke (AIS) after endovascular thrombectomy (EVT). We retrospectively collected 150 patients with AIS who underwent pre-treatment CT perfusion (CTP) evaluation and subsequent EVT from April 2018 to April 2022. Three-phases (peak arterial phase, peak venous phase, late venous phase) CTA was reconstructed from CTP raw data, and VO was evaluated on three-phases CTA, respectively. Favorable VO was regarded as a cortical vein opacification score of 3-6, and unfavorable VO as a score of 0-2. Good outcome was defined as modified Rankin Scale score of 0-2 at 90 days after EVT. Multivariate logistic regression analysis was performed to explore the predictors of good outcome. Prognostic value was assessed and compared using receiver operating characteristic (ROC) curves and Delong test. We found that good outcome was achieved in 85 (56.7%) patients. Among the mCTA-derived VO profiles, only favorable peak venous phase VO was found to be independently associated with good outcome (P < 0.001). After integrating favorable peak venous phase VO with lower post-treatment National Institute of Health Stroke Scale score at 24 hours, successful recanalization and favorable hypoperfusion intensity ratio, the predictive ability for a good outcome was significantly improved than before (area under the ROC curve; 0.947 vs 0.881; P = 0.002). This study supports that favorable peak venous VO profiles on mCTA might be a promising biomarker in predicting the good outcome in patients with AIS after EVT.

Sijunzi decoction granules in the prevention and treatment of recurrence of colorectal adenoma: Study protocol for a multicenter, randomized, double-blind, placebo-controlled trial.

Background: The recurrence of colorectal adenomas (CRAs) after endoscopy predisposes patients to a risk of colorectal cancer. Guided by the traditional Chinese medicine (TCM), patients with colorectal diseases usually manifest with spleen deficiency syndrome (SDS) and are treated with Sijunzi decoction (SJZD). Therefore, this trial aims to explore the efficacy and safety of SJZD in the prevention and treatment of CRAs recurrence. Methods: SJZD on prevention and treatment of CRAs recurrence after resection: a multicenter, randomized, double-blind, placebo-controlled trial was designed. Patients who undergo polypectomy of CRAs will be recruited and randomized into a SJZD group and a placebo group in a 1:1 ratio. The intervention phase will be 12 months. The follow-up period will last 24 months. The primary outcome is the CRA recurrence rate after intervention. The secondary outcomes include the CRA recurrence rate at the second year post-polypectomy, the pathological type of adenoma and the alterations in SDS scores after intervention. Discussion: Previous clinical practice has observed the sound effect of SJZD in the context of gastrointestinal diseases. A number of experiments have also validated the active components in SJZD. This trial aims to provide tangible evidence for the usage of SJZD, hoping to reduce the recurrence of CRAs.

[The effects of leptin on apoptosis of airway smooth muscle cells via the PI3K/Akt signaling pathway].

OBJECTIVE: To observe the effects of leptin on the expression of Akt, Pho-Akt, Bcl-2, Bax, caspase-3 and the apoptosis of airway smooth muscle cells (ASMCs), and to explore the possible mechanisms. METHODS: ASMCs were derived from rat airway tissue and cultured in vitro. The cells were randomly divided into 5 groups including a control group, leptin at concentrations of 50, 100, 200 µg/L groups (group Lep50, Lep100, Lep200), and PI3K specific antagonist with Lep200 group. Then the cells of different groups were incubated for 24 h. An apoptosis detection kit was used for annexin V and PI staining. The expression of Akt, phosphorylation Akt, Bcl-2, Bax, caspase-3 were measured by Western blot. RESULTS: The apoptosis rates of ASMCs in group Lep50, Lep100 and Lep200 were (3.97 ± 0.39)%, (1.88 ± 0.72)% and (0.77 ± 0.11)%, respectively, all significantly lower than that in the control group (7.38 ± 0.49)% (F = 89.57, P < 0.05). Furthermore, the concentration of leptin was negatively related to the apoptosis rate (r = -0.711, P < 0.05). The apoptosis rates of PI3K specific antagonist with Lep200 group (3.29 ± 0.36)% was higher than that of group Lep200 (0.77 ± 0.11)% (F = 89.57, P < 0.01). After the intervention of leptin, the expression of Bcl-2 was upregulated and positively correlated with leptin concentration (r = 0.939, P < 0.05); Bax was downregulated and negatively related to the leptin concentration (r = -0.908, P < 0.05); while the Bcl-2/Bax ratio was raised after leptin treatment (F = 20.56, P < 0.05). Leptin inhibited the activation of caspase-3 in the negative way. (r = -0.961, P < 0.05). The results also showed that leptin significantly increased phosphorylation of Akt that positively related to leptin concentration (r = 0.958, P < 0.05). Compared with group Lep200, the expression of Pho-Akt and Bcl-2 in PI3K specific antagonist with Lep200 group were downregulated (F = 32.93, 19.48, respectively, P < 0.05), while the expression of Bax and caspase-3 was increased (F = 10.10, 29.86, respectively, P < 0.05); the Bcl-2/Bax ratio was lower in group Lep200 as compared to the PI3K specific antagonist with Lep200 group (F = 20.56, P < 0.05). CONCLUSION: Leptin can significantly inhibit ASMC apoptosis partially via the PI3K/Akt signaling pathway.

Time-synchronic comments on video streaming website reveal core structures of audience engagement in movie viewing.

To what extent movie viewers are swept into a fictional world has long been pondered by psychologists and filmmakers. With the development of time-synchronic comments on online viewing platforms, we can now analyze viewers' immediate responses toward movies. In this study, we collected over 3 million Chinese time-synchronic comments from a video streaming website. We first assessed emotion and cognition-related word rates in these comments with the Simplified Chinese version of the Linguistic Inquiry and Word Count (SCLIWC) and applied time-series clustering to the word rates. Then Hierarchical Density-Based Spatial Clustering of Applications with Noise (HDBSCAN) was conducted on the text to investigate the prevalent topics among the comments. We found different commenting behaviors in front of various movies and prototypical diachronic trajectories of the psychological engagement of the audience. We further identified how topics are discussed through time, and tried to account for viewer's engagement, considering successively movie genres, topics and movie content. Among other points, we finally discussed the challenge in explaining the trajectories of engagement and the disconnection with narrative content. Overall, our study provides a new perspective on using social media data to answer questions from psychology and film studies. It underscores the potential of time-synchronic comments as a resource for detecting real-time human responses to specific events.

The role of grammatical role and thematic role predictability in reference form production in Mandarin Chinese.

Evidence suggests that English speakers use pronouns when referring to the grammatical subject and predictable thematic role. We tested how grammatical role and thematic role predictability affect different types of referential forms, namely, overt pronouns and null pronouns in Mandarin Chinese. We found that both overt and null pronouns were sensitive to grammatical role. However, we did not find any evidence that overt and null pronouns were sensitive to thematic role predictability. Although null pronouns were influenced by grammatical role, the rate of null pronouns for subject reference was very low compared to that of overt pronouns. Given the frequent occurrence of null pronouns in Mandarin, our results suggest that the use of null pronouns may not be explained by a simple grammatical role mechanism.

Laboratory detection of SARS-CoV-2: A review of the current literature and future perspectives.

Nowadays, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), whose infectivity is awfully strong, has been a major global threat to the public health. Since lung is the major target of SARS-CoV-2, the infection can lead to respiratory distress syndrome (RDS), multiple organ failure (MOF), and even death. The studies on viral structure and infection mechanism have found that angiotensin-converting enzyme 2 (ACE2), a pivotal enzyme affecting the organ-targeting in the RAS system, is the receptor of the SARS-CoV-2 virus. Currently, the detection of SARSCoV-2 is mainly achieved using open plate real-time reverse-transcription polymerase chain reaction (RT-PCR). While open plate method has some limitations, such as a high false-negative rate, cumbersome manual operation, aerosol pollution and leakage risks. Therefore, a convenient method to rapidly detect SARS-CoV-2 virus is urgently and extremely required for timely epidemic control with the limited resources. In this review, the current real-time methods and principles for novel coronavirus detection are summarized, with the aim to provide a reference for real-time screening of coronavirus in areas with insufficient detection capacity and inadequate medical resources. The development and establishment of a rapid, simple, sensitive and specific system to detect SARS-CoV-2 is of vital importance for distinct diagnosis and effective treatment of the virus, especially in the flu season.

[Saxagliptin alleviates kidney injury in diabetic rats by down-regulating the expression of mammalian target of rapamycin (mTOR)].

Objective To investigate the effect of saxagliptin (Sax) against kidney injury in diabetic rats and its mechanisms. Methods SD male rats were fed for 2 weeks, among which 14 rats were selected randomly and given intraperitoneal injection of streptozotocin (STZ) to establish the type 2 diabetes mellitus (T2DM) model, and then were randomly divided into T2DM group and Sax group after the model was successfully established; 6 rats were selected as normal control (NC) group randomly. The rats of Sax group were given the saxagliptin solution. The rats of NC and T2DM groups were injected with the same amount of sodium carboxymethyl cellulose solution. After 8 weeks of continuous gastric administration, the rats were sacrificed and their blood and kidney tissues were collected. Glucose (G1u), albumin (ALB), aspartate transaminase (AST), alanine transaminase (ALT), serum creatinine (Scr), blood urea nitrogen (BUN), uric acid (UA), serum total cholesterol (TC), triglycerides (TG) were detected by automatic biochemical analyzer. HE, PAS, Masson staining and transmission electron microscopy were performed to observe the morphological changes of renal. Immunohistochemical staining was used to detect the protein expression level of mammalian target of rapamycin (mTOR), interleukin 1 (IL-1), IL-6, tumor necrosis factor α (TNF-α) in renal tissues. Results Compared with the NC group, the levels of biochemical indicators such as G1u, ALB, AST, ALT, Scr, BUN, UA, TC, and TG showed significant increase; the number of glomerular mesangial cells also increased, and the mesangial matrix hyperplasia, mTOR, IL-1, IL-6, TNF-α protein expression levels exhibited significant increase in T2DM group. Compared with T2DM group, Sax group showed decreased levels of biochemical indicators such as G1u, ALB, AST, ALT, Scr, BUN, UA, TC, and TG and improved renal pathological damage performance, together with a profound reduction in mTOR, IL-1, IL-6, TNF-α protein expression level. Conclusion Sax may suppress inflammatory response and reduce renal injury in diabetic rats by down-regulating mTOR expression.

Therapeutic efficacy of dapagliflozin on diabetic kidney disease in rats.

AIM: Diabetic kidney disease (DKD) is one of the severe microvascular complications of type 2 diabetes mellitus (T2DM), which eventually leads to irreversible renal damage and develops into end-stage renal disease (ESRD). Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a new class of antidiabetic drugs that act on the kidney to reduce glucose reabsorption. Increasing evidence confirms that dapagliflozin exerts a protective effect on DKD, but the mechanisms have not been reported. The aims of this study were to observe the therapeutic efficacy of dapagliflozin on DKD and investigate the possible immunological mechanism. MATERIALS AND METHODS: T2DM was modeled by a high-sugar and high-fat diet combined with STZ. Then, rats were treated with 10 mg/kg dapagliflozin for 8 weeks. The protective efficacy of dapagliflozin was evaluated by observing body weight, blood glucose, blood serum creatinine, blood urea nitrogen, 24-h urine protein, renal histology and ultrastructure, and oxidative stress levels. The immunological mechanisms were monitored by measuring the levels of TLR2/Myd88/NF-κB by immunohistochemical staining, RT-qPCR and Western blotting. RESULTS: After treatment with dapagliflozin, renal damage was greatly improved. The levels of blood glucose, renal function and proteinuria were significantly decreased, and renal pathological and ultrastructural damage was obviously extenuated, possibly due to the reduction in inflammation and the levels of oxidative stress. CONCLUSIONS: Dapagliflozin has therapeutic potential for DKD. This effect was possibly mediated by inhibiting inflammation and oxidative stress levels.