Prognoses of Patients Treated With Surgical Therapy Versus Continuation of Local-Plus-Systemic Therapy Following Successful Down-Staging of Intermediate-Advanced Hepatocellular Carcinoma: A Multicenter Real-World Study.

BACKGROUND: The difference in the prognoses between treatment with surgical therapy and continuation of local-plus-systemic therapy following successful down-staging of intermediate-advanced hepatocellular carcinoma (HCC) remains unclear. METHODS: Data of 405 patients with intermediate-advanced HCC treated at 30 hospitals across China from January 2017 to July 2022 were retrospectively reviewed. All patients received local-plus-systemic therapy and were divided into the surgical (n = 100) and nonsurgical groups (n = 305) according to whether they received surgical therapy. The differences between long-term prognoses of the 2 groups were compared. Subgroup analysis was performed in 173 HCC patients who met the criteria for surgical resection following down-staging. RESULTS: Multivariable analysis of all patients showed that surgical therapy, hazard ratio (HR): 0.289, 95% confidence interval, CI, 0.136-0.613) was a protective factor for overall survival (OS), but not for event-free survival (EFS). Multivariable analysis of 173 intermediate-advanced HCC patients who met the criteria for surgical resection after conversion therapy showed that surgical therapy (HR: 0.282, 95% CI, 0.121-0.655) was a protective factor for OS, but not for EFS. Similar results were obtained after propensity score matching. For patients with Barcelona Clinic Liver Cancer stage B (HR: 0.171, 95% CI, 0.039-0.751) and C (HR: 0.269, 95% CI, 0.085-0.854), surgical therapy was also a protective factor for OS. CONCLUSIONS: Overall, for patients with intermediate-advanced HCC who underwent local-plus-systemic therapies, surgical therapy is a protective factor for long-term prognosis and can prolong OS, and for those who met the surgical resection criteria after conversion therapy, surgical therapy is recommended.

Aveir VR real-world performance and chronic pacing threshold prediction using mapping and fixation electrical data.

AIMS: Aveir VR performance and predictors for its pacing threshold (PCT) in a real-world cohort were investigated. METHODS: Electrical measurements at various stages of an Aveir VR implant were prospectively collected. Predictors for 3-month PCT were studied. A retrospective cohort of consecutive 139 Micra implants was used to compare the PCT evolution. High PCT was defined as ≥1.5 V, using a pulse width of 0.4 ms for Aveir and 0.24 ms for Micra. Excellent PCT was defined as ≤0.5 V at the respective pulse width. RESULTS: Among the 123 consecutive Aveir VR implant attempts, 122 (99.2%) were successful. The majority were of advanced age (mean 79.7) and small body size (mean BSA 1.60). Two patients (1.6%) experienced complications, including one pericardial effusion after device reposition and one intraoperative device dislodgement. Eighty-eight patients reached a 3-month follow-up. Aveir 3-month PCT was correlated with impedance at mapping (P = 0.015), tether mode (P < 0.001), end-of-procedure (P < 0.001), and mapping PCT (P = 0.035), but not with PCTs after fixation (P > 0.05). Tether mode impedance >470 ohms had 88% sensitivity and 71% specificity in predicting excellent 3-month PCT. Although it is more common for Aveir to have high PCT at end of procedure (11.5% for Aveir and 2.2% for Micra, P = 0.004), the rate at 3 months was similar (2.3% for Aveir and 3.1% for Micra, P = 1.000). CONCLUSION: Aveir VR demonstrated satisfactory performance in this high-risk cohort. Pacing thresholds tend to improve to a greater extent than Micra after implantation. The PCT after fixation, even after a waiting period, has limited predictive value for the chronic threshold. Low-mapping PCT and high intraoperative impedance predict chronic low PCT.

Highly Luminescent Earth-Benign Organometallic Manganese Halide Crystals with Ultrahigh Thermal Stability of Emission from 4 to 623 K.

The phosphor-converted light-emitting diode (PC-LED) has become an indispensable solid-state lighting and display technologies in the modern society. Nevertheless, the use of scarce rare-earth elements and the thermal quenching (TQ) behavior are still two most crucial issues yet to be solved. Here, this work successfully demonstrates a highly efficient and thermally stable green emissive MnI2 (XanPO) crystals showing a notable photoluminescence quantum yield (PLQY) of 94% and a super TQ resistance from 4 to 623 K. This unprecedented superior thermal stability is attributed to the low electron-phonon coupling and the unique rigid crystal structure of MnI2 (XanPO) over the whole temperature range based on the temperature-dependent photoluminescence (PL) and single crystal X-ray diffraction (SCXRD) analyses. Considering these appealing properties, green PC-LEDs with a power efficacy of 102.5 lm W-1 , an external quantum efficiency (EQE) of 22.7% and a peak luminance up to 7750 000 cd m-2 are fabricated by integrating MnI2 (XanPO) with commercial blue LEDs. Moreover, the applicability of MnI2 (XanPO) in both micro-LEDs and organic light-emitting diodes (OLEDs) is also demonstrated. In a nutshell, this study uncovers a candidate of highly luminescent and TQ resistant manganese halide suitable for a variety of emission applications.

Highly Efficient MAPbI3 -Based Quantum Dots Exhibiting Unusual Nonblinking Single Photon Emission at Room Temperature.

Highly emissive semiconductor nanocrystals, or so-called quantum dots (QDs) possess a variety of applications from displays and biology labeling, to quantum communication and modern security. Though ensembles of QDs have already shown very high photoluminescent quantum yields (PLQYs) and have been widely utilized in current optoelectronic products, QDs that exhibit high absorption cross-section, high emission intensity, and, most important, nonblinking behavior at single-dot level have long been desired and not yet realized at room temperature. In this work, infrared-emissive MAPbI3 -based halide perovskite QDs is demonstrated. These QDs not only show a ≈100% PLQY at the ensemble level but also, surprisingly, at the single-dot level, display an extra-large absorption cross-section up to 1.80 × 10-12 cm2 and non-blinking single photon emission with a high single photon purity of 95.3%, a unique property that is extremely rare among all types of quantum emitters operated at room temperature. An in-depth analysis indicates that neither trion formation nor band-edge carrier trapping is observed in MAPbI3 QDs, resulting in the suppression of intensity blinking and lifetime blinking. Fluence-dependent transient absorption measurements reveal that the coexistence of non-blinking behavior and high single photon purity in these perovskite QDs results from a significant repulsive exciton-exciton interaction, which suppresses the formation of biexciton, and thus greatly reduces photocharging. The robustness of these QDs is confirmed by their excellent stability under continuous 1 h electron irradiation in high-resolution transmission electron microscope inspection. It is believed that these results mark an important milestone in realizing nonblinking single photon emission in semiconductor QDs.

3'-epi-12ß-hydroxyfroside-mediated autophagy degradation of RIPK1/RIPK3 necrosomes leads to anergy of immunogenic cell death in triple-negative breast cancer cells.

Increasing studies have suggested that some cardiac glycosides, such as conventional digoxin (DIG) and digitoxin, can induce immunogenic cell death (ICD) in various tumors. We previously found that 3'-epi-12ß-hydroxyfroside (HyFS), a novel cardenolide compound isolated by our group, could induce cytoprotective autophagy through inactivation of the Akt/mTOR pathway. However, whether HyFS can induce ICD remains unknown. In this study, we extend our work to further investigate whether HyFS could induce both autophagy and ICD, and we investigated the relationship between autophagy and ICD in three TNBC cell lines. Unexpectedly, compared to DIG, we found that HyFS could induce complete autophagy flux but not ICD in three human triple-negative breast cancer (TNBC) cell lines and one murine TNBC model. Inhibition of HyFS-induced autophagy resulted in the production of ICD in TNBC MDA-MB-231, MDA-MB-436, and HCC38 cells. A further mechanism study showed that formation of RIPK1/RIPK3 necrosomes was necessary for ICD induction in DIG-treated TNBC cells, while HyFS treatment led to receptor-interacting serine-threonine kinase (RIPK)1/3 necrosome degradation via an autophagy process. Additionally, inhibition of HyFS-induced autophagy by the autophagy inhibitor chloroquine resulted in the reoccurrence of ICD and reversion of the tumor microenvironment, leading to more significant antitumor effects in immunocompetent mice than in immunodeficient mice. These findings indicate that HyFS-mediated autophagic degradation of RIPK1/RIPK3 necrosomes leads to inactivation of ICD in TNBC cells. Moreover, combined treatment with HyFS and an autophagy inhibitor may enhance the antitumor activities, suggesting an alternative therapeutic for TNBC treatment.

Spatio-Temporally Reporting Dose-Dependent Chemotherapy via Uniting Dual-Modal MRI/NIR Imaging.

Unpredictable in vivo therapeutic feedback of hydroxyl radical (. OH) efficiency is the major bottleneck of chemodynamic therapy. Herein, we describe novel Fenton-based nanotheranostics NQ-Cy@Fe&GOD for spatio-temporally reporting intratumor . OH-mediated treatment, which innovatively unites dual-channel near-infrared (NIR) fluorescence and magnetic resonance imaging (MRI) signals. Specifically, MRI signal traces the dose distribution of Fenton-based iron oxide nanoparticles (IONPs) with high-spatial resolution, meanwhile timely fluorescence signal quantifies . OH-mediated therapeutic response with high spatio-temporal resolution. NQ-Cy@Fe&GOD can successfully monitor the intracellular release of IONPs and . OH-induced NQO1 enzyme in living cells and tumor-bearing mice, which makes a breakthrough in conquering the inherent unpredictable obstacles on spatio-temporally reporting chemodynamic therapy, so as to manipulate dose-dependent therapeutic process.

Mid-term Results of a Novel Dedicated Venous Stent for the Treatment of Chronic Thoracic Central Vein Obstruction of Benign Aetiology.

OBJECTIVES: Endovascular treatment is indicated for the treatment of symptomatic thoracic central vein obstruction (TCVO) but is limited by high rates of restenosis and the need for re-intervention. The aim was to assess the safety and mid-term patency of a novel dedicated venous stent for the treatment of TCVO of benign aetiology. METHODS: This was a prospective single centre observational study of 20 patients (median age 65 years, 50% male) referred for the treatment of symptomatic chronic (>three months duration) TCVO between May 2016 and January 2018. Balloon angioplasty with implantation of a self expanding nitinol stent (Vici, Boston Scientific, Marlborough, MA, USA) was performed in all patients. Clinical records including demographics, aetiologies and types of TCVO, and procedural details were recorded. Patients were followed up clinically at one, six, and 12 months. Primary and assisted primary patency were reported. RESULTS: All 20 lesions were total occlusions, of which 55% (n = 11) were de novo, 10% (n = 2) peri-stent restenosis, and 35% (n = 7) in-stent re-occlusion. The aetiology of TCVO was predominantly (95%) because of multiple or prolonged central venous line insertion. The procedural success rate was 90% (18/20) with no procedural complications. The median follow up was 13.5 months. Primary patency was 100% at 6 months. One patient required re-intervention for stent in segment restenosis at 7 months. The assisted primary patency rate was 100% at 12 months. CONCLUSION: Endovascular treatment of benign TCVO with the novel dedicated venous stent was safe and effective in relieving obstructive symptoms with excellent one year patency rates.

PEG-dBSA-RuS1.7 Nanoclusters as a NIR Light and pH Responsive Drug Delivery Nanoplatform for Chemo-Photothermal Synergistic Therapy.

A combination of chemotherapy and photothermal therapy has emerged as a promising method of cancer treatment since it can enhance therapeutic efficacies and reduce side effects. Herein, we fabricated doxorubicin (DOX) loaded PEG-dBSA-RuS1.7 which could be used as a synergistic therapeutic nanoplatform. The PEG-dBSA-RuS1.7/DOX nanoparticles exhibit good monodispersity, physiological stability and biocompatibility. Moreover, the prepared PEG-dBSA-RuS1.7/DOX nanoparticles can intelligently release DOX by pH- and NIR-triggered therapy. In comparison with chemotherapy or photothermal treatment alone, the combined therapy shows a better therapeutic effect. We believe that the PEG-dBSA-RuS1.7/DOX can act as an efficient multifunctional nanoplatform for chemophotothermal synergistic cancer therapy.

The Emerging Role of Cables1 in Cancer and Other Diseases.

Cdk5 and Abl enzyme substrate 1 (Cables1) is an adaptor protein that links cyclin-dependent kinase (Cdks) with nonreceptor tyrosine kinases and regulates the activity of Cdks by enhancing their Y15 phosphorylation. Emerging evidence also shows that Cables1 can interact with, for example, p53 family proteins, 14-3-3, and ß-catenin, suggesting that Cables1 may be a signaling hub for the regulation of cell growth. Abnormal expression of Cables1 has been observed in multiple types of cancers and other diseases. In this review, we summarize the characteristics of Cables1 and highlight the molecular mechanisms through which Cables1 regulates the development of cancer and other diseases. Finally, we discuss future challenges in demonstrating the role and potential application of Cables1 in cancer and other diseases.

MicroRNA-638 inhibits cell proliferation by targeting suppress PIM1 expression in human osteosarcoma.

MicroRNAs (miRNAs) are a type of small noncoding RNAs that often play important roles in carcinogenesis, but the carcinogenic mechanism of miRNAs is still unclear. This study will investigate the functions and the mechanism of miR-638 in osteosarcoma (OS). The expression of miR-638 in OS and the DNA copy number of miR-638 were detected by real-time PCR. The effect of miR-638 on cell proliferation was measured by CCK8 assay. Different assays, including bioinformatics algorithms, luciferase report assay, and Western blotting, were used to identify the target gene proviral integration site for Moloney murine leukemia virus 1 (PIM1) of miR-638 in OS. The expression of PIM1 in clinical OS tissues was also validated by immunohistochemical assay. From this research, we found that miR-638 was downregulated in OS tissues compared with corresponding noncancerous tissues (NCTs), and the DNA copy number of miR-638 was lower in OS than in NCTs, which may induce the corresponding downregulation of miR-638 in OS. Ectopic expression of miR-638 inhibited OS cell growth in vitro. Subsequently, we identified that PIM1 is the downstream target gene of miR-638 in OS cells, and silencing PIM1 expression phenocopied the inhibitory effect of miR-638 on OS cell proliferation. Furthermore, we observed that PIM1 was overexpressed in OS tissues, and high expression of PIM1 in OS predicted poor overall survival. In summary, we revealed that miR-638 functions as a tumor suppressor through inhibiting PIM1 expression in OS.

Anti-tumor effects of a recombinant anti-prostate specific membrane antigen immunotoxin against prostate cancer cells.

BACKGROUND: To evaluate anti-prostate cancer effects of a chimeric tumor-targeted killer protein. METHODS: We established a novel fusion gene, immunocasp-3, composed of NH2-terminal leader sequence fused with an anti-prostate-specific membrane antigen (PSMA) antibody (J591), the furin cleavage sequences of diphtheria toxin (Fdt), and the reverse coding sequences of the large and small subunits of caspase-3 (revcaspase-3). The expressing level of the immunocasp-3 gene was evaluated by using the reverse transcription-PCR (RT-PCR) and western blot analysis. Cell viability assay and cytotoxicity assay were used to evaluate its anti-tumor effects in vitro. Apoptosis was confirmed by electron microscopy and Annexin V-FITC staining. The antitumor effects of immunocasp-3 were assessed in nude mice xenograft models containing PSMA-overexpressing LNCaP cells. RESULTS: This study shows that the immunocasp-3 proteins selectively recognized and induced apoptotic death in PSMA-overexpressing LNCaP cells in vitro, where apoptotic cells were present in 15.3% of the cells transfected with the immunocasp-3 expression vector at 48 h after the transfection, in contrast to 5.5% in the control cells. Moreover, LNCaP cells were significantly killed under the condition of the co-culture of the immunocasp-3-secreting Jurkat cells and more than 50% of the LNCaP cells died when the two cell lines were co-cultured within 5 days. In addition, The expression of immunocasp-3 also significantly suppressed tumor growth and greatly prolonged the animal survival rate in vivo. CONCLUSION: A novel fusion gene, immunocasp-3, may represent a viable approach to treating PSMA-positive prostate cancer.

Overexpression of pyruvate kinase M2 predicts a poor prognosis for patients with osteosarcoma.

It is stated that high expression of pyruvate kinase (PKM2) emerges as a significant player in the metabolism and progression of various human malignancies. However, the expression of PKM2 and its association with the prognosis of osteosarcoma had not yet been studied. In the present study, the expression and biological significance of PKM2 in osteosarcoma were investigated. We found that PKM2 expression was elevated in the cancerous tissues and it was more abundant than the adjacent normal tissues (60.2 vs 26.1 %, p < 0.001). Moreover, we showed that high PKM2 expression was positively correlated with Enneking stage (p = 0.006) and distant metastasis (p = 0.007) but not with the age, gender, tumor site, tumor size, histologic grade, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and local pain of the patients. Furthermore, Kaplan-Meier analysis revealed that the overall survival (OS) for patients with high PKM2 expression was significantly lower than those with low PKM2 expression (p < 0.001). Finally, multivariate analysis revealed that high PKM2 expression was an independent prognostic factor for osteosarcoma patients (p = 0.004). Collectively, these data indicated that elevated PKM2 might serve as a novel target for the treatment of osteosarcoma.

Relationship of the Serum CRP Level With the Efficacy of Metformin in the Treatment of Type 2 Diabetes Mellitus: A Meta-Analysis.

BACKGROUND: Metformin, an anti-diabetes drug, is always used as a first-line agent for the management of T2DM. This meta-analysis was conducted to investigate whether CRP was sensitive in predicting the efficacy of metformin in the treatment of T2DM. METHODS: Potential relevant studies were identified covering the following databases: MEDLINE, Science Citation Index database, the Cochrane Library Database, PubMed, EMBASE, CINAHL, Current Contents Index, the Chinese Biomedical Database, the Chinese Journal Full-Text Database, and the Weipu Journal Database. Data from eligible studies were extracted and included into the meta-analysis using a random effects model. Statistical analyses were calculated using the version 12.0 STATA software. RESULTS: A total of 33 articles including 1,433 subjects were collected for analysis. Pooled SMD of those studies revealed that serum levels of CRP and hs-CRP significantly decreased in patients with T2DM after receiving the metformin treatment. Subgroup analysis by country yielded significant different estimates in the serum levels of CRP between the baseline and after metformin treatment in the China, Israel and India subgroups; but only detected only in the China subgroup considering serum levels of hs-CRP. Follow-up time-stratified analyses indicated that serum levels of CRP were markedly reduced in the metformin-treated group in all subgroups. While differences in serum hs-CRP levels were not observed in two subgroups. CONCLUSION: Decreased serum levels of CRP and hs-CRP may contribute to a more sensitive prediction in providing a more accurate efficacy reference in the metformin drug in T2DM patients.

Strophalloside induces apoptosis of SGC-7901 cells through the mitochondrion-dependent caspase-3 pathway.

Cardenolides with special chemical structures have been considered as effective anti-cancer drugs in clinic trials. Strophalloside is a cardenolide we recently isolated from Antiaris toxicaria obtained from Hainan, China. The aim of this study was to investigate the possible anticancer effects induced by strophalloside and the underlying molecular mechanism. Gastric carcinoma SGC-7901 cells were treated with strophalloside at various concentrations for different times, and resulting cell viability was determined by the MTT assay, and the motility and invasion of tumor cells were assessed by the Transwell chamber assay. Apoptosis were measured by Annexin V-FITC/PI and Hoechst staining. The changes of mitochondrial transmembrane potential were examined by a JC-1 kit. The expressions of pro-apoptotic protein cytochrome c, caspase-3 and caspase-9 were detected by western blotting analysis. The results showed that strophalloside was capable of reducing cell viability, inhibiting cell growth, and suppressing cell migration and invasion in a time- and dose-dependent manner. Mitochondrial membrane potential declined and the concentration of cytochrome c increased in cytoplasm and caspase-3 and caspase-9 were cleaved into activated states, suggesting that cytochrome c was released from the mitochondrion to cytoplasm and finally activated the caspase-dependent apoptosis pathway. Our results indicate that strophalloside is a potential anticancer drug.

Antigen 43/Fcε3 chimeric protein expressed by a novel bacterial surface expression system as an effective asthma vaccine.

The IgE Fcε3 domain is an active immunotherapeutic target for asthma and other allergic diseases. However, previous methods for preparing IgE fusion protein vaccines are complex. Antigen 43 (Ag43) is a surface protein found in Escherichia coli that contains α and ß subunits (the α subunit contains multiple T epitopes). Here we constructed a novel Ag43 surface display system (Ag43 system) to express Ag43 chimeric proteins to disrupt immune tolerance against IgE. The Ag43 system was constructed from the E. coli strain Tan109, in which the Ag43 gene was deleted and a recombinant plasmid (pETAg43) expressing a partial Ag43 gene was introduced. The Fcε3 domain of the IgE gene was then subcloned into plasmid pETAg43, resulting in a recombinant plasmid pETAg43/Fcε3, which was used to transform Tan109 for Ag43/Fcε3 surface expression. Thereafter, Ag43/Fcε3 was investigated as an asthma vaccine in a mouse model. Ag43/Fcε3 was expressed on and could be separated from the bacterial surface by heating to 60° while retaining activity. Ag43/Fcε3, as a protein vaccine, produced neutralizing autoantibodies to murine IgE, induced significant anti-asthma effects, and regulated IgE and T helper cytokines in a murine asthma model. Data show that Ag43/Fcε3 chimeric protein is a potential model vaccine for asthma treatment, and that the Ag43 system may be an effective tool for novel vaccine preparation to break immune tolerance to other self-molecules.

Bacterial surface display of endoglin by antigen 43 induces antitumor effectiveness via bypassing immunotolerance and inhibition of angiogenesis.

Various angiogenesis-related self-molecules have been considered to be therapeutic targets. However, the direct use of self-molecules as vaccines is not recommended because of the inherent ability of the host to develop immune tolerance. Antigen 43 (Ag43) is a surface protein found in E. coli and contains an α and a ß subunits, which contains multiple T epitopes in α subunit. Here we construct a novel Ag43 surface display system (Ag43 system) to express Ag43 chimeric proteins to disrupt immune tolerance against self-molecules. The Ag43 system was constructed from an Escherichia coli strain Tan109, derived from JM109, in which the Ag43 gene was deleted and a recombinant plasmid (pETAg43') expressing a partial Ag43 gene was introduced. The extracellular domain of angiogenesis-related endoglin gene was then subcloned into plasmid pETAg43', resulting in a recombinant plasmid pETAg43'/END(e) which was then used to transform Tan109 for protein expression. We found that Ag43 and endoglin chimeric protein (Ag43'/END(e) ) was expressed on the bacterial surface. The chimeric protein could be separated from the bacterial surface by heating to 60°C and yet retain activity. We used Ag43'/END(e) as a protein vaccine and found that it could disrupt immune tolerance against endoglin by inducing significant antitumor activities and inhibit angiogenesis in several tumor models without significant side effects. These data suggest that Ag43'/END(e) chimeric protein is a potential model vaccine for active tumor immunotherapy, and that Ag43 system could be an effective tool for novel vaccine preparation to break immune tolerance to other angiogenesis-related self-molecules for cancer therapy.

Screening and analysis of metabolites in rat urine after oral administration of Apocynum venetum L. extracts using HPLC-TOF-MS.

HPLC with diode array detection and ESI-TOF-MS was used for the study of the constituents in Apocynum venetum L. extracts and the metabolites in rat urine after oral administration of A. venetum L. extracts. A formula database of the known constituents in A. venetum L. was established, and 21 constituents were rapidly identified by accurately matching their molecular masses with the formulae of the compounds in the database. Furthermore, 34 metabolites were detected and elucidated in the rat urine. The scientific and plausible biotransformation pathways of the flavonoid components in A. venetum L. were also proposed together with the presentation of clues for potential mechanisms of bioactivity. This specific and sensitive HPLC-ESI-TOF-MS method can be used to identify the chemical components in the extracts of A. venetum L. and their metabolites in rat urine. This method can also be used to reveal the possible metabolic mechanisms of action of the extract components in vivo.

Sanpao herbs inhibit development of atopic dermatitis in Balb/c mice.

OBJECTIVE: To explore the effects of SANPAOCAO (SPC), a compound traditional Chinese folk medicine, on chronic dermatitis/eczema in mice induced by 2, 4-dinitrochlorobenzene (DNCB). METHODS: Thirty-three Balb/c mice were randomly divided into a negative control group, a positive control group, a prednisolone treatment group, an SPC ethanol extract treatment group, a Cardiospermum halicacabum ethanol extract treatment group, a Physalis minima ethanol extract treatment group, and a Jussiaea repens ethanol extract treatment group. Mice in the six treatment groups had twenty-five microliters of 0.1% DNCB in acetone/olive oil (3: 1) applied to each side of their right ears and dorsal skin three times a week, over a 5 week period. They were treated with prednisolone or the various kinds of ethanol extract after each challenge. The weight difference between the two ears, pathological changes in the right ears, dermal inflammatory cell numbers, and total serum Ig E levels were used to assess the effects of the drugs. RESULTS: after the 5 weeks of challenges, the weight differences of the ears in the SPC group and the prednisolone group were significantly less than those in the other groups. There was evidence of significant suppression of the development of dermatitis, as determined by a histological examination and the serum Ig E levels. CONCLUSION: SPC has beneficial effects when used in the treatment of chronic dermatitis-eczema in mice.

Identifying Proteins and Amino Acids Associated with Liver Cancer Risk: A Study Utilizing Mendelian Randomization and Bulk RNA Sequencing Analysis.

BACKGROUND: Primary liver cancer (PLC) ranks third in terms of fatality rate among all malignant tumors worldwide. Proteomics and metabolomics have become widely utilized in identifying causes and diagnostic indicators of PLC. Nevertheless, in studies aiming to identify proteins/metabolites that experienced significant changes before PLC, the potential impact of reverse causation and confounding variables still needs to be fully addressed. METHODS: This study thoroughly investigated the causal relationship between 4719 blood proteins, 21 amino acids, and the risk of PLC using the Mendelian randomization (MR) method. In addition, through a comprehensive analysis of the TCGA-LIHC cohort and GEO databases, we evaluated the differentially expressed genes (DEGs) related to serine metabolism in diagnosing and predicting the prognosis of patients with PLC. RESULTS: A total of 63 proteins have been identified as connected to the risk of PLC. Additionally, there has been confirmation of a positive cause-effect between PLC and the concentration of serine. The integration of findings from both MR analyses determined that the protein associated with PLC risk exhibited a significant correlation with serine metabolism. Upon careful analysis of the TCGA-LIHC cohort, it was found that eight DEGs are linked to serine metabolism. After thoroughly validating the GEO database, two DEGs, TDO2 and MICB, emerged as potential biomarkers for diagnosing PLC. CONCLUSIONS: Two proteins involved in serine metabolism, MICB and TDO2, are causally linked to the risk of PLC and could potentially be used as diagnostic indicators.

Sex and gender differences in social participation among community-dwelling older adults: a systematic review.

Background: Frequent social participation among older adults is associated with greater health. Although understanding how sex and gender influence social participation is important, particularly in developing sex-inclusive health promotion and preventive interventions, little is known about factors influencing engagement of older women and men in social activities. Aim: This study thus aimed to examine factors influencing social activities of older women and men. Methods: A mixed-method systematic review was conducted in nine electronic databases from inception to March 2023. The studies had to define social participation as activities with others and examine its influencing factors among community-dwelling older women and men. Data were analyzed using convergent synthesis design from a socio-ecological perspective. Results: Forty-nine studies, comprising 42 quantitative, five qualitative and two mixed method design were included. Themes identified concerned: (a) sociodemographic factors, (b) personal assets, (c) interpersonal relationships and commitments, (d) physical environment, and (e) societal norms and gender expectations. The findings identified the heterogeneous needs, preferences and inequalities faced by older women and men, considerations on sociocultural expectations and norms of each gender when engaging in social activities, and the importance of having adequate and accessible social spaces. Overall, this review identified more evidence on factors influencing social participation among women than in men. Conclusion: Special attention is needed among community care providers and healthcare professionals to co-design, implement or prescribe a combination of sex and gender-specific and neutral activities that interest both older women and men. Intersectoral collaborative actions, including public health advocates, gerontologists, policymakers, and land use planners, are needed to unify efforts to foster social inclusion by creating an age-friendly and sustainable healthy environment. More longitudinal studies are required to better understand social participation trajectories from a sex and gender perspective and identify factors influencing it. Systematic reviews registration: http://www.crd.york.ac.uk/PROSPERO, identifier [CRD42023392764].