Time-/dose- series transcriptome data analysis and traditional Chinese medicine treatment of pneumoconiosis.

Pneumoconiosis' pathogenesis is still unclear and specific drugs for its treatment are lacking. Analysis of series transcriptome data often uses a single comparison method, and there are few reports on using such data to predict the treatment of pneumoconiosis with traditional Chinese medicine (TCM). Here, we proposed a new method for analyzing series transcriptomic data, series difference analysis (SDA), and applied it to pneumoconiosis. By comparison with 5 gene sets including existing pneumoconiosis-related genes and gene set functional enrichment analysis, we demonstrated that the new method was not inferior to two existing traditional analysis methods. Furthermore, based on the TCM-drug target interaction network, we predicted the TCM corresponding to the common pneumoconiosis-related genes obtained by multiple methods, and combined them with the high-frequency TCM for its treatment obtained through literature mining to form a new TCM formula for it. After feeding it to pneumoconiosis modeling mice for two months, compared with the untreated group, the coat color, mental state and tissue sections of the mice in the treated group were markedly improved, indicating that the new TCM formula has a certain efficacy. Our study provides new insights into method development for series transcriptomic data analysis and treatment of pneumoconiosis.

Effectiveness of acceptance and commitment therapy in people with type 2 diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Acceptance and commitment therapy (ACT) is a psychotherapy technique, which promotes psychological flexibility and enables patients to change behaviors based on value-directed goals. However, the beneficial effects of ACT on glycemic control, self-care behaviors, acceptance of diabetes, self-efficacy, and psychological burden are still unclear among patients with type 2 diabetes mellitus (T2DM). AIMS: This study aimed to systematically synthesize scientific evidence to determine the effectiveness of ACT among patients with T2DM on glycemic control, self-care behaviors, acceptance of diabetes, self-efficacy, and psychological burden and identify the optimal characteristics of effective interventions. METHODS: Nine electronic databases were searched to identify eligible studies of randomized controlled trials from inception to June 2023. Two reviewers independently assessed the study eligibility, extracted the data, and performed the quality appraisal using the Cochrane Risk of Bias 2 Tool. The meta-analysis was conducted using Review Manager 5.3. The certainty of the evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation system. RESULTS: Ten studies involving 712 participants were included. ACT demonstrated significant improvements on patients' glycemic control (mean difference [MD]: 0.95%; p < .001), self-care behaviors (MD: 1.86; p = .03), diabetes acceptance (MD: 7.80; p < .001), self-efficacy (standardized mean difference [SMD]: 1.04; p < .001), anxiety (SMD: -1.15; p = .006), and depression (SMD: -1.10; p = .04). However, favorable but nonsignificant improvements were found in diabetes distress. Subgroup analyses demonstrated that ACT offered more than five sessions using individualized format, with theoretical underpinnings and professional input from multidisciplinary therapists are recommended to yield better results on glycemic control and self-care behaviors. LINKING EVIDENCE TO ACTION: Acceptance and commitment therapy could generate beneficial effectiveness on glycemic control, self-care behaviors, acceptance of diabetes, self-efficacy, anxiety, and depression among patients with T2DM. Large-scale trials with rigorous design and representative samples are warranted to strengthen the current evidence.

Elucidation of the mechanism of action of ailanthone in the treatment of colorectal cancer: integration of network pharmacology, bioinformatics analysis and experimental validation.

Background: Ailanthone, a small compound derived from the bark of Ailanthus altissima (Mill.) Swingle, has several anti-tumour properties. However, the activity and mechanism of ailanthone in colorectal cancer (CRC) remain to be investigated. This study aims to comprehensively investigate the mechanism of ailanthone in the treatment of CRC by employing a combination of network pharmacology, bioinformatics analysis, and molecular biological technique. Methods: The druggability of ailanthone was examined, and its targets were identified using relevant databases. The RNA sequencing data of individuals with CRC obtained from the Cancer Genome Atlas (TCGA) database were analyzed. Utilizing the R programming language, an in-depth investigation of differentially expressed genes was carried out, and the potential target of ailanthone for anti-CRC was found. Through the integration of protein-protein interaction (PPI) network analysis, GO and KEGG enrichment studies to search for the key pathway of the action of Ailanthone. Then, by employing molecular docking verification, flow cytometry, Transwell assays, and Immunofluorescence to corroborate these discoveries. Results: Data regarding pharmacokinetic parameters and 137 target genes for ailanthone were obtained. Leveraging The Cancer Genome Atlas database, information regarding 2,551 differentially expressed genes was extracted. Subsequent analyses, encompassing protein-protein interaction network analysis, survival analysis, functional enrichment analysis, and molecular docking verification, revealed the PI3K/AKT signaling pathway as pivotal mediators of ailanthone against CRC. Additionally, the in vitro experiments indicated that ailanthone substantially affects the cell cycle, induces apoptosis in CRC cells (HCT116 and SW620 cells), and impedes the migration and invasion capabilities of these cells. Immunofluorescence staining showed that ailanthone significantly inhibited the phosphorylation of AKT protein and suppressed the activation of the PI3K/AKT signaling pathway, thereby inhibiting the proliferation and metastasis of CRC cells. Conclusion: Therefore, our findings indicate that Ailanthone exerts anti-CRC effects primarily by inhibiting the activation of the PI3K/AKT pathway. Additionally, we propose that Ailanthone holds potential as a therapeutic agent for the treatment of human CRC.

Lenvatinib combined with sintilimab plus transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma.

BACKGROUND: Recently, combination therapy has shown a better trend towards improved tumour response and survival outcomes than monotherapy in patients with hepatocellular carcinoma (HCC). However, research on triple therapy [lenvatinib + sintilimab + transarterial chemoembolization (TACE)] as a first-line treatment for advanced HCC is limited. AIM: To evaluate the safety and efficacy of triple therapy as a first-line treatment for advanced HCC. METHODS: HCC patients with Barcelona Clinic Liver Cancer stage C treated with triple therapy were enrolled. All patients were treated with lenvatinib every day and sintilimab once every 3 wk. Moreover, TACE was performed every 4-6 wk if necessary. The primary outcome of the study was overall survival (OS). The secondary outcomes were the objective response rate (ORR), disease control rate (DCR), and incidence of adverse events. RESULTS: Forty HCC patients who underwent triple therapy were retrospectively analysed from January 2019 to January 2022. With a median follow-up of 8.5 months, the 3-, 6-, and 12-mo OS rates were 100%, 88.5%, and 22.5%, respectively. The ORR and DCR were 45% and 90%, respectively. The median progressive free survival and median OS were not reached. Common complications were observed in 76% of the patients (grade 3, 15%; grade 4, 2.5%). CONCLUSION: Combination therapy comprising lenvatinib, sintilimab and TACE achieved promising outcomes in advanced HCC patients and had manageable effects.

Investigating the mechanism of Sinisan formula in depression treatment: a comprehensive analysis using GEO datasets, network pharmacology, and molecular docking.

The herbal formula Sinisan (SNS) is a commonly used treatment for depression; however, its mechanism of action remains unclear. This article uses a combination of the GEO database, network pharmacology and molecular docking technologies to investigate the mechanism of action of SNS. The aim is to provide new insights and methods for future depression treatments. The study aims to extract effective compounds and targets for the treatment of depression from the T CMSP database. Relevant targets were searched using the GEO, Disgenet, Drugbank, PharmGKB and T T D databases, followed by screening of core targets. In addition, GO and KEGG pathway enrichment analyses were performed to explore potential pathways for the treatment of depression. Molecular docking was used to evaluate the potential targets and compounds and to identify the optimal core protein-compound complex. Molecular dynamics was used to further investigate the dynamic variability and stability of the complex. The study identified 118 active SNS components and 208 corresponding targets. Topological analysis of P P I networks identified 11 core targets. GO and KEGG pathway enrichment analyses revealed that the mechanism of action for depression involves genes associated with inflammation, apoptosis, oxidative stress, and the MAP K3 and P I3K-Akt signalling pathways. Molecular docking and dynamics simulations showed a strong binding affinity between these compounds and the screened targets, indicating promising biological activity. The present study investigated the active components, targets and pathways of SNS in the treatment of depression. Through a preliminary investigation, key signalling pathways and compounds were identified. These findings provide new directions and ideas for future research on the therapeutic mechanism of SNS and its clinical application in the treatment of depression.Communicated by Ramaswamy H. Sarma.

Nasal spray of an IgM-like ACE2 fusion protein HH-120 prevents SARS-CoV-2 infection: Two investigator-initiated postexposure prophylaxis trials.

HH-120, an IgM-like angiotensin converting enzyme 2 (ACE2) fusion protein, has been developed as a nasal spray against Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is currently undergoing human trials. HH-120 nasal spray was assessed for postexposure prophylaxis (PEP) in two investigator-initiated (NS01 and NS02) trials with different risk levels of SARS-CoV-2 exposure. NS01 enrolled family caregiver participants who had continuous contacts with laboratory-confirmed index cases; NS02 enrolled participants who had general contacts (Part 1) or close contacts (Part 2) with index cases. The primary endpoints were safety and laboratory-confirmed and/or symptomatic SARS-CoV-2 infection. In NS01 trial (14 participants), the SARS-CoV-2 infection rates were 25% in the HH-120 group and 83.3% in the external control group (relative risk reduction [RRR]: 70.0%). In NS02-Part 1 (193 participants), the infection rates were 4% (HH-120) versus 11.3% (placebo), symptomatic infection rates were 0.8% versus 3.5%, hence with a RRR of 64.6% and 77.1%, respectively. In Part 2 (76 participants), the infection rates were 17.1% (HH-120) versus 30.4% (placebo), symptomatic infection rates were 7.5% versus 27.3%, with a RRR of 43.8% and 72.5%, respectively. No HH-120-related serious adverse effects were observed. The HH-120 nasal spray used as PEP was safe and effective in preventing laboratory-confirmed and symptomatic SARS-CoV-2 infection.

Network pharmacology and molecular docking to study the potential molecular mechanism of Qi Fu Yin for diabetic encephalopathy.

Diabetic encephalopathy is a chronic complication of diabetes that lacks an optimized treatment strategy. The present study sought to elucidate the potential molecular mechanism of Qi Fu Yin in improving diabetic encephalopathy through network pharmacology. The active components and target information of Qi Fu Yin were obtained from the TCMSP and Swiss target databases, while the target information of diabetic encephalopathy was sourced from Gene cards, OMIM, and Pharm Gkb databases. Enrichment analyses of KEGG and GO were conducted utilizing drug-disease common targets, while protein-protein interactions were predicted through the utilization of the STRING database platform. Subsequently, molecular docking was executed via Auto Dock Vina to authenticate the interaction between core components and core targets. The findings revealed that Qi Fu Yin exhibited 178 common targets with diabetic encephalopathy, and the enrichment analyses demonstrated that these targets were associated with lipid and atherosclerosis, AGE-RAGE signaling pathways, and other related pathways. The findings of the molecular docking indicated a favorable binding affinity between the active components of drug and the core targets, with EGF and quercetin exhibiting the most notable docking score. Additionally, the molecular dynamics simulation corroborated this high affinity. These results suggested that the active ingredients of Qi Fu Yin, including quercetin and kaempferol, may modulated the expression of genes such as IL10, TNF, EGF, and MMP2, thereby activating the AGE-RAGE signaling pathways and potentially serving as a therapeutic intervention for diabetic encephalopathy.Communicated by Ramaswamy H. Sarma.

Serial mediation roles of empowerment and self-care activities connecting health literacy, quality of life, and glycemic control in people with type 2 diabetes.

BACKGROUND: Health literacy, empowerment, and self-care activities are likely the crucial concepts affecting the quality of life and glycemic control in people with type 2 diabetes (T2D). However, evidence demonstrating the mechanisms underlying these concepts is scarce. AIMS: The aim of this study was to test the serial mediation roles of empowerment and self-care activities on the relationships between health literacy and quality of life and between health literacy and hemoglobin A1c (HbA1c) in people with T2D. METHODS: A cross-sectional study was conducted among 319 people with T2D in Guangzhou, China, from July 2019 to January 2020. Data were collected using the Health Literacy Scale, the Diabetes Empowerment Scale-Short Form, the Summary of Diabetes Self-Care Activities Measure, and the Adjusted Diabetes-Specific Quality of Life Scale. RStudio 4.2.1 was used for serial mediation analysis. RESULTS: The dimension of communicative health literacy accounted for the most total variance (ß = 0.810, p < .001) in the construct of health literacy. The serial multiple mediation of empowerment and self-care activities in the associations between health literacy and quality of life (ß = -.046, p = .019) and between health literacy and HbA1c (ß = -.045, p = .005) were statistically significant. LINKING EVIDENCE TO ACTION: This study emphasized the vital role of communicative health literacy when improving health literacy in people with T2D. Diabetes care and education specialists could implement empowerment approaches and flexible self-care strategies to improve the quality of life and glycemic control in people with T2D. Enhancing health literacy was suggested as a favorable strategy for promoting empowerment and self-care activities in people with T2D.

Nasal spray of an IgM-like ACE2 fusion protein HH-120 accelerates SARS-CoV-2 clearance: A single-center propensity score-matched cohort study.

HH-120, a recently developed IgM-like ACE2 fusion protein with broad-spectrum neutralizing activity against all ACE2-utilizing coronaviruses, has been developed as a nasal spray for use as an early treatment agent to reduce disease progression and airborne transmission. The objective of this study was to evaluate the safety and efficacy of the HH-120 nasal spray in SARS-CoV-2-infected subjects. Eligible symptomatic or asymptomatic SARS-CoV-2-infected participants were enrolled in a single-arm trial to receive the HH-120 nasal spray for no longer than 6 days or until viral clearance at a single hospital between August 3 and October 7, 2022. An external control was built from real-world data of SARS-CoV-2-infected subjects contemporaneously hospitalized in the same hospital using a propensity score matching (PSM) method. After PSM, 65 participants in the HH-120 group and 103 subjects with comparable baseline characteristics in the external control group were identified. The viral clearance time was significantly shorter in participants receiving the HH-120 nasal spray than that in subjects of the control group (median 8 days vs. 10 days, p < 0.001); the difference was more prominent in those subgroup subjects with higher baseline viral load (median 7.5 days vs. 10.5 days, p < 0.001). The incidence of treatment-emergent adverse events and treatment-related adverse events of HH-120 group were 35.1% (27/77) and 3.9% (3/77), respectively. All the adverse events observed were mild, being of CTCAE grade 1 or 2, and transient. The HH-120 nasal spray showed a favorable safety profile and promising antiviral efficacy in SARS-CoV-2-infected subjects. The results from this study warrant further assessment of the efficacy and safety of the HH-120 nasal spray in large-scale randomized controlled clinical trials.

A lipid metabolism-based prognostic risk model for HBV-related hepatocellular carcinoma.

BACKGROUND: Up to 85% of hepatocellular carcinoma (HCC) cases in China can be attributed to infection of hepatitis B virus (HBV). Lipid metabolism performs important function in hepatocarcinogenesis of HBV-related liver carcinoma. However, limited studies have explored the prognostic role of lipid metabolism in HBV-related HCC. This study established a prognostic model to stratify HBV-related HCC based on lipid metabolisms. METHODS: Based on The Cancer Genome Atlas HBV-related HCC samples, this study selected prognosis-related lipid metabolism genes and established a prognosis risk model by performing uni- and multi-variate Cox regression methods. The final markers used to establish the model were selected through the least absolute shrinkage and selection operator method. Analysis of functional enrichment, immune landscape, and genomic alteration was utilized to investigate the inner molecular mechanism involved in prognosis. RESULTS: The risk model independently stratified HBV-infected patients with liver cancer into two risk groups. The low-risk groups harbored longer survival times (with P < 0.05, log-rank test). TP53, LRP1B, TTN, and DNAH8 mutations and high genomic instability occurred in high-risk groups. Low-risk groups harbored higher CD8 T cell infiltration and BTLA expression. Lipid-metabolism (including "Fatty acid metabolism") and immune pathways were significantly enriched (P < 0.05) in the low-risk groups. CONCLUSIONS: This study established a robust model to stratify HBV-related HCC effectively. Analysis results decode in part the heterogeneity of HBV-related liver cancer and highlight perturbation of lipid metabolism in HBV-related HCC. This study's findings could facilitate patients' clinical classification and give hints for treatment selection.

Emerging Roles of Meningeal Lymphatic Vessels in Alzheimer's Disease.

Meningeal lymphatic vessels (mLVs), the functional lymphatic system present in the meninges, are the key drainage route responsible for the clearance of molecules, immune cells, and cellular debris from the cerebrospinal fluid and interstitial fluid into deep cervical lymph nodes. Aging and ApoE4, the two most important risk factors for Alzheimer's disease (AD), induce mLV dysfunction, decrease cerebrospinal fluid influx and outflux, and exacerbate amyloid pathology and cognitive dysfunction. Dysfunction of mLVs results in the deposition of metabolic products, accelerates neuroinflammation, and promotes the release of pro-inflammatory cytokines in the brain. Thus, mLVs represent a novel therapeutic target for treating neurodegenerative and neuroinflammatory diseases. This review aims to summarize the structure and function of mLVs and to discuss the potential effect of aging and ApoE4 on mLV dysfunction, as well as their roles in the pathogenesis of AD.

Elevated TAF12 Expression Predicts Poor Prognosis in Glioma Patients: Evidence from Bioinformatic and Immunohistochemical Analyses.

TATA box-binding protein-associated factor 12 (TAF12) has been identified as an oncogene in choroid plexus carcinoma, but its role in glioma is poorly understood because of a lack of previous studies. This study investigated the relationship of TAF12 expression with the clinicopathologic features of glioma cases, as well as its prognostic value and biological function, using large-scale databases and clinical samples. TAF12 mRNA expression and clinicopathologic characteristics of glioma cases were assessed in three public databases, and bioinformatics analyses were conducted to explore the prognostic value and biological functions of TAF12 in glioma. High TAF12 expression was commonly associated with reduced survival time and poor clinical indexes, including higher World Health Organization grade, wild-type isocitrate dehydrogenase 1 expression, and 1p19q non-codeletion status (p < 0.0001). Multivariate Cox regression analysis showed that high TAF12 expression was an independent poor prognostic factor for glioma patients (hazard ratio = 1.41, 95% confidence interval, 1.18-1.68, p < 0.001). Functional enrichment analysis revealed involvement of TAF12 in immune and inflammatory responses in glioma. Also, expression of several immune checkpoint molecules was significantly higher in samples with high TAF12 expression. TAF12 is a potential independent prognostic factor for glioma, and these findings provide a foundation for further investigation of the potential role of TAF12 in immunotherapy.

Galectin-9/Tim-3 pathway mediates dopaminergic neurodegeneration in MPTP-induced mouse model of Parkinson's disease.

Galectin-9 (Gal-9) is a crucial immunoregulatory mediator in the central nervous system. Microglial activation and neuroinflammation play a key role in the degeneration of dopaminergic neurons in the substantia nigra (SN) in Parkinson's disease (PD). However, it remains unknown whether Gal-9 is involved in the pathogenesis of PD. We found that MPP+ treatment promoted the expression of Gal-9 and pro-inflammatory cytokines (IL-6, IL-1ß, TNF-α, and MIP-1α) in a concentration-dependent manner in BV2 cells. Gal-9 enhanced neurodegeneration and oxidative stress induced by MPP+ in SH-SY5Y cells and primary neurons. Importantly, deletion of Gal-9 or blockade of Tim-3 ameliorated microglial activation, reduced dopaminergic neuronal loss, and improved motor performance in an MPTP-induced mouse model of PD. These observations demonstrate a pathogenic role of the Gal-9/Tim-3 pathway in exacerbating microglial activation, neuroinflammation, oxidative stress, and dopaminergic neurodegeneration in the pathogenesis of PD.

CT-guided percutaneous chemical ablation combined with radiofrequency ablation for hepatocellular carcinomas in high-risk locations: lobaplatin vs. ethanol.

To retrospectively compare the clinical efficacy and safety of CT-guided percutaneous injection of lobaplatin vs. ethanol for chemical ablation combined with radiofrequency ablation (RFA) in patients with hepatocellular carcinomas (HCCs) in high-risk locations. From January 2017 to June 2018, a total of 41 patients with HCCs in high-risk locations were enrolled and divided into two groups: percutaneous lobaplatin injection (PLI+RFA) group and percutaneous ethanol injection (PEI+RFA) group. The mixture of lobaplatin or ethanol was accurately injected into the high-risk part of the tumors, while RFA ablated the non-high-risk part. The efficacy and safety were compared between the two groups. 41 patients had 51 lesions in high-risk locations, including 24 cases with 30 lesions in PLI+RFA group and 17 cases with 21 lesions in PEI+RFA group. The complete ablation rate was 93.3% (28/30) in PLI+RFA group and 90.5% (19/21) in PEI+RFA group (P=1.000). The 2-year local tumor progression rate of PLI+RFA group and PEI+RFA group was 20.0% (6/30) and 19.0% (4/21), respectively (P=1.000). No significant differences were found in time to progression and overall survival between the two groups (P=0.501 and P=0.424, respectively). The incidence and severity of adverse events between the two groups were similar (P > 0.05). No severe complications were observed in both groups. Percutaneous lobaplatin injection combined with RFA in the treatment of HCC in high-risk locations may achieve the complete ablation rate similar to percutaneous ethanol injection combined with RFA, but further research is needed to confirm.

Molecular docking assisted exploration on solubilization of poorly soluble drug remdesivir in sulfobutyl ether-tycyclodextrin.

Objective: To study structure-specific solubilization effect of Sulfobutyl ether-ß-cyclodextrin (SBE-ß-CD) on Remdesivir (RDV) and to understand the experimental clathration with the aid of quantum mechanics (QM), molecular docking and molecular dynamics (MD) calculations. Methods: The experiment was carried out by phase solubility method at various pH and temperatures, while the concentration of Remdesivir in the solution was determined by HPLC. The complexation mechanism and the pH dependence of drug loading were investigated following a novel procedure combining QM, MD and molecular docking, based on accurate pKa predictions. Results: The phase solubility and solubilization effect of RDV in SBE-ß-CD were explored kinetically and thermodynamically for each assessed condition. An optimal drug / SBE-ß-CD feeding molar ratio was determined stoichiometrically for RDV solubility in pH1.7 solution. The supersaturated solubility was examined over time after pH of the solution was adjusted from 1.7 to 3.5. A possible hypothesis was raised to elucidate the experimentally observed stabilization of supersaturation based on the proposed RDV Cation A /SBE-ß-CD pocket conformations. Conclusion: The computational explorations conformed to the experimentally determined phase solubilization and well elucidated the mechanism of macroscopic clathration between RDV and SBE-ß-CD from the perspective of microscopic molecular calculations.

Transarterial chemoembolization plus lenvatinib versus transarterial chemoembolization plus sorafenib as first-line treatment for hepatocellular carcinoma with portal vein tumor thrombus: A prospective randomized study.

BACKGROUND: The efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) have not been evaluated. METHODS: In this open-label, single-center, randomized trial (ClinicalTrials.gov identifier: NCT04127396), participants with previously untreated HCC and type I-IV PVTT were randomized 1:1 to receive TACE plus lenvatinib (arm L; orally once daily, 12 mg for body weight ≥60 kg or 8 mg for body weight <60 kg) or TACE plus sorafenib (arm S; 400 mg orally twice daily in 28-day cycles). The primary end point was time-to-progression (TTP; time from randomization to disease progression) and secondary end points included objective response rate and toxicity. Prognostic factors were evaluated using a multivariable Cox proportional hazards model. RESULTS: Between December 30, 2018 and May 31, 2020, 64 patients were randomized (arm L, n = 32; arm S, n = 32); most patients had type I/II PVTT (71.9%), and the median target tumor diameter was 9.8 cm (range, 3.8-21.8). After a median follow-up of 16.1 months, patients in arm L had a higher median TTP (4.7 vs 3.1 months; hazard ratio [HR], 0.55; 95% CI, 0.32-0.95; P = .029) and objective response rate (53.1% vs 25.0%, P = .039) versus arm S. Multivariable analysis showed that TACE plus lenvatinib was significantly associated with higher TTP versus TACE plus sorafenib (HR, 0.50; 95% CI, 0.28-0.90; P = .021). Comparable safety profiles were observed in arms L and S. CONCLUSIONS: TACE plus lenvatinib was safe, well tolerated, and had favorable efficacy versus TACE plus sorafenib in patients with advanced HCC with PVTT and large tumor burden. LAY SUMMARY: Hepatocellular carcinoma with portal vein tumor thrombus has a poor prognosis. In addition, most phase 3 trials of drugs for hepatocellular carcinoma exclude patients with major portal vein invasion, and treatment options for these patients are limited. Transarterial chemoembolization has shown promising efficacy in these patients, especially in combination with systemic treatment or radiotherapy. However, transarterial chemoembolization plus lenvatinib has not been investigated in this setting. This open-label, single-center, randomized trial showed that transarterial chemoembolization plus lenvatinib is safe, well tolerated, and has favorable efficacy versus transarterial chemoembolization plus sorafenib for the treatment of hepatocellular carcinoma with portal vein tumor thrombus.

Liposomal honokiol promotes hair growth via activating Wnt3a/ß-catenin signaling pathway and down regulating TGF-ß1 in C57BL/6N mice.

Liposomal honokiol isolated from the genus Magnolia has been found to have antiangiogenic, anti-inflammatory and antitumor properties. However, there has no report on its role in hair growth. Hair follicles are life-long cycled organelles that go through from anagen, catagen and telogen stages and are regulated by diverse signaling pathways, including Wnt/ß-catenin, Notch, Epidermal growth factor (EGF) and Sonic hegehog (SHH). Wnt signals are essential for the initiation of hair follicle placode development and a new potential target of hair loss treatment. This study was designed to investigate the effect of liposomal honokiol (Lip-honokiol) on inducing hair anagen. We identified the hair grew out in advance in the shaving area of C57BL/6N mice after the treatment of liposomal honokiol (Lip-honokiol) by daily abdominal injection. We first demonstrated that Lip-Honokiol activated the Wnt3a/ß-catenin pathway and downregulated the transforming growth factor-ß1 (TGF-ß1) to promote hair growth in mice via immunohistochemistry and immunofluorescence staining. These findings suggest that Lip-honokiol activated the Wnt/ß-catenin pathway and accelerated the transfer from the telogen to anagen stage and finally promoted the hair growth.

Efficacy and Safety of a Decision Support Intervention for Basal Insulin Self-Titration Assisted by the Nurse in Outpatients with T2DM: A Randomized Controlled Trial.

OBJECTIVE: The main aim of this study was to evaluate a combined fasting blood glucose based dosage self-titration setting and decision supported telephone coaching intervention on glycemic control and diabetes self-management skills, compared to the conventional care. METHODS: A 12-week, single-blinded, randomized controlled trial was conducted on adults with type 2 diabetes (T2DM) primarily treated with basal insulin. After randomization, the intervention group (IG, n = 426) received a basal insulin self-titration decision support intervention administered by the Diabetes Specialty Nurses while the control group (CG, n = 423) received conventional care for 12 weeks, both included five telephone interviews. The primary efficacy endpoint was the effect of intervention on glycemic control, measured as the change in glycated hemoglobin (HbA1c) from baseline to Week 12 (after intervention) compared to the control group. Other endpoints included comparisons of the effects of intervention on fasting plasma glucose (FPG), postprandial plasma glucose (PPG), body weight, Michigan diabetes knowledge test (MDKT), diabetes empowerment scale-short Form (DES-DSF), and summary of diabetes self-care activities (SDSCA). Changes in the primary and secondary outcomes were compared using the t-test for continuous variables with a normal distribution and χ 2-test for categorical variables. RESULTS: The IG showed more improvements on mean HbA1c, compared to the CG (-2.8% vs -1.8%), so did the FPG, PPG, MDKT, DES-DSF and SDSCA (all P<0.01) after the 12-week follow up. Though the final mean insulin dose in the IG was higher than the CG at the end of the study (0.32 U/kg vs 0.28 U/kg), the changes of body weight were similar between the two groups (0.46kg vs 0.40kg, P=0.246), and the proportion of patients with hypoglycemia events during the whole trial were similar (20.65% vs 17.73%, P=0.279). CONCLUSION: Decision supporting of basal insulin glargine self-titration assisted by Diabetes Specialty Nurses is effective and safe in patients with T2DM. Decision supported telephone coaching intervention offers ongoing encouragement, guidance, and determination of relevant sources of decisional conflict, facilitating adjusting the insulin dose.

Dietary Knowledge, Attitude and Practice (KAP) Among the Family Members of Patients with Type 2 Diabetes Mellitus (T2DM) and Its Influence on the KAP of T2DM Patients.

PURPOSE: To investigate the dietary knowledge, attitude and practice (KAP) among the family members (FMs) of Chinese type 2 diabetes mellitus (T2DM) patients and its influence on the KAP of T2DM patients. PATIENTS AND METHODS: Two hundred thirty-six pairs of hospitalized T2DM patients and their FMs (472 in total) in our hospital were enrolled. A pair of self-designed questionnaires on dietary KAP (Cronbach's α ≥ 0.763, I-CVI ≥ 0.857, S-CVI = 0.964, 0.958) were used to collect data and assess the KAP towards diabetes diets. RESULTS: The mean score for dietary KAP of T2DM patients was 2.33 ± 0.60, 3.03 ± 0.44 and 2.77 ± 0.38, whereas that of their FMs was 2.37 ± 0.55, 3.08 ± 0.48 and 2.82 ± 0.61, respectively. Pearson's correlation analysis showed that the glycosylated hemoglobin (HbA1c) of T2DM patients was negatively correlated to their dietary practice (r = -0.218, P < 0.01). There was a positive correlation between T2DM patients and their FMs for dietary KAP (r = 0.306, P < 0.05). The dietary practice of T2DM patients was positively correlated with the dietary KAP of their FMs (r = 0.305, 0.252 and 0.136, respectively, P < 0.01). Logistic regression analysis revealed that the score for dietary knowledge and attitude, occupation, residence, family history, complications of the T2DM patient, and the sex and dietary knowledge score of the FM were significantly associated with dietary practice for T2DM patients. CONCLUSION: The dietary attitude of FMs was moderate but dietary knowledge and practice were poor. Dietary KAP was positively correlated with T2DM patients and their FMs.

Specific dynamic variations in the peripheral blood lymphocyte subsets in COVID-19 and severe influenza A patients: a retrospective observational study.

BACKGROUND: Both COVID-19 and influenza A contribute to increased mortality among the elderly and those with existing comorbidities. Changes in the underlying immune mechanisms determine patient prognosis. This study aimed to analyze the role of lymphocyte subsets in the immunopathogenesisof COVID-19 and severe influenza A, and examined the clinical significance of their alterations in the prognosis and recovery duration. METHODS: By retrospectively reviewing of patients in four groups (healthy controls, severe influenza A, non-severe COVID-19 and severe COVID-19) who were admitted to Ditan hospital between 2018 to 2020, we performed flow cytometric analysis and compared the absolute counts of leukocytes, lymphocytes, and lymphocyte subsets of the patients at different time points (weeks 1-4). RESULTS: We reviewed the patients' data of 94 healthy blood donors, 80 Non-severe-COVID-19, 19 Severe-COVID-19 and 37 severe influenza A. We found total lymphocytes (0.81 × 109/L vs 1.74 × 109/L, P = 0.001; 0.87 × 109/L vs 1.74 × 109/L, P < 0.0001, respectively) and lymphocyte subsets (T cells, CD4+ and CD8+ T cell subsets) of severe COVID-19 and severe influenza A patients to be significantly lower than those of healthy donors at early infection stages. Further, significant dynamic variations were observed at different time points (weeks 1-4). CONCLUSIONS: Our study suggests the plausible role of lymphocyte subsets in disease progression, which in turn affects prognosis and recovery duration in patients with severe COVID-19 and influenza A.