Berberine attenuates 5-fluorouracil-induced intestinal mucosal injury by modulating the gut microbiota without compromising its anti-tumor efficacy.

Background: 5-Fluorouracil (5-Fu), a prominent chemotherapeutic agent for colorectal cancer (CRC) treatment, is often associated with gastrointestinal toxicities, particularly diarrhea. Our previous study demonstrated that berberine (BBR) ameliorates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota in rats. Nevertheless, the precise molecular mechanism underlying BBR's protective effect on intestinal mucosa remains elusive, and its impact on the anti-tumor efficacy of 5-Fu warrants further investigation. Methods: The effect of BBR on 5-Fu-induced intestinal mucosal injury was investigated using a tumor-bearing murine model, employing H&E staining, 16 S rDNA sequencing, transcriptome sequencing, Western blot analysis, cell experiments and constructing a pseudo-germ-free tumor xenograft model. Result: Our findings demonstrate that BBR alleviates intestinal mucosal damage, reduces the levels of inflammatory factors (IL-6, TNF-α, and IL-1ß), and inhibits epithelial cell apoptosis in 5-Fu-treated mice without compromising 5-Fu's anti-tumor efficacy. Moreover, 16 S rDNA sequencing indicated that BBR significantly increases the abundance of Akkermansia and decreases the abundance of pathogenic bacteria Escherichia/Shigella at the genus level. Mechanistically, transcriptome sequencing and Western blot analysis confirmed that BBR upregulates PI3K/AKT/mTOR expression in the intestinal mucosa. However, this effect was not observed in tumor tissues. Notably, BBR did not demonstrate a direct protective effect on 5-Fu-treated CCD841 and SW480 cells. Additionally, BBR had no effect on the PI3K/AKT/mTOR pathway in the intestinal tissue of the 5-Fu-treated mouse model with a depleted gut microbiota. Conclusion: This study indicates that BBR alleviates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota and regulating the PI3K/AKT/mTOR signaling pathway without compromising the anti-tumor efficacy of 5-Fu.

Resveratrol by elevating the SIRT1 BDNF, GDNF and PSD95 levels reduce heroin addiction related behaviors.

OBJECTIVE: To study the effects of resveratrol on heroin addiction-related behaviors and to preliminarily explore the possible intervention mechanism of resveratrol in heroin dependence. METHODS: The effects of resveratrol on heroin withdrawal symptoms were observed by naloxone; The effect of resveratrol on heroin reward memory acquisition was detected by CPP paradigm; The effect of resveratrol on the mental excitability of heroin was tested by open field experiment; The effect of resveratrol on heroin spatial learning and memory was tested by water maze test. Western blot was used to detect Sirtuin 1 (SIRT1) Expression of brain-derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF), and postsynaptic density protein (PSD95). RESULTS: The behavioral results showed that the withdrawal behavior of the resveratrol intervention group was reduced compared with the heroin chronic dependence group (P<0.05), and the shift score of the conditioned place preference test of the resveratrol intervention group was reduced compared with the heroin chronic dependence group (P<0.05) The spatial learning and memory ability of the water maze in the resveratrol intervention group was improved compared with the heroin chronic dependence group (P<0.05), and the mental excitability of the resveratrol intervention group was lower than that of the heroin chronic dependence group (P<0.05), but higher than that of the saline group (P<0.05); SIRT1 The expression levels of BDNF, GDNF and PSD95 protein were significantly increased (P<0.05). CONCLUSION: The behavioral results of this study suggest that resveratrol can be used as a potential drug to treat heroin dependence. At the same time, SIRT1 The expression of BDNF, GDNF, and PSD95 increased; SIRT1, BDNF, GDNF, and PSD95 play an essential role in heroin addiction.

Zonular ligament abnormalities intermingled in acute primary angle closure: A diagnostic and therapeutic challenge.

Purpose: This study aims to investigate patient characteristics with lens zonular ligament abnormalities in Acute Primary Angle Closure (APAC), identifying related risk factors, and evaluating the efficacy of Pilocarpine, a miotic agent. Design: Retrospective case-control study. Methods: Conducted as a retrospective case-control study at Hebei Provincial Eye Hospital from January 1, 2019, to December 31, 2021, the study included APAC cases undergoing ultrasound phacoemulsification with or without glaucoma surgery. Zonular ligament status was determined by intraoperative indicators such as lens equator visibility post-mydriasis and anterior capsule wrinkling during capsulorhexis. Patients were categorized into APAC and APAC with Lens Subluxation (APACLS) groups. Demographic details, Central Anterior Chamber Depth (ACD), Axial Length (AL), ACD difference between eyes (ACDD), Lens Thickness (LT), Lens Position (LP), and Relative Lens Position (RLP) were recorded and compared. Pilocarpine's impact on intraocular pressure reduction was assessed. Statistical analysis involved bilateral t-tests (for normally distributed data comparing both eyes in each group), non-parametric tests (for comparing two groups with non-normally distributed data), binary logistic regression, and Receiver Operating Characteristic (ROC) curve analysis for cutoff value determination related to zonular abnormalities. Results: The APAC and APACLS groups showed no significant difference in age of onset (70.11 ± 8.67 years vs. 70.11 ± 8.67 years, P = 0.159) or axial length of the eye (22.35 ± 0.64 mm vs. 22.36 ± 0.78 mm, P = 0.929). In the APACLS group, LT was greater (5.24 ± 0.37 mm vs. 5.01 ± 0.36 mm, P = 0.011), ACD was shallower (1.42 ± 0.24 mm vs. 1.69 ± 0.24 mm, P = 0.000), and ACDD was larger (0.38 ± 0.22 mm vs. 0.18 ± 0.18 mm, P = 0.000). The LP was lower (4.04 ± 0.32 vs. 4.20 ± 0.22, P = 0.013), and RLP was also lower (0.18 ± 0.02 vs. 0.19 ± 0.01, P = 0.015) in the APACLS group. A shallow ACD and a large ACDD were identified as risk factors associated with lens zonular abnormalities in the affected eyes (ACD OR value 63.97, P = 0.027; ACDD OR value 0.029, P = 0.027). Using ROC curve analysis, the cutoff value for ACDD was determined to be 0.375 mm, and for ACD, it was 1.6 mm. After pupil constriction with Pilocarpine eye drops, the proportion of patients whose intraocular pressure normalized was 75.36 % (52/69) in the APAC group and 71.43 % (25/35) in the APACLS group. Conclusion: ACD and ACDD in the affected eye are indicative of increased risk for APACLS. An ACD <1.6 mm and ACDD >0.375 mm should prompt consideration of zonular ligament abnormalities. Pilocarpine as a miotic treatment is safe and effective for such patients.

Fifteen acute retrobulbar optic neuritis associated with COVID-19: A case report and review of literature.

BACKGROUND: A subtype of the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is suggested to be responsible for the outbreak in Northern China since the quarantine was lifted in December 2022. The coronavirus disease 2019 virus is primarily responsible for the development of respiratory illnesses, however, it can present a plethora of symptoms affecting a myriad of body organs. This virus has been theorized to be linked to demyelinating lesions of the peripheral and central nervous system including transverse myelitis and acute retrobulbar optic neuritis (ARON). For example, magnetic resonance imaging (MRI) of the orbit and brain showed enlargement of the retrobulbar intraorbital segments of the optic nerve with high T2 signal, and no abnormalities were seen in the brain tissue. In this case series, we analyzed the connection between SARS-CoV-2 infection and the onset of ARON. CASE SUMMARY: Fifteen patients, and a teenage boy who did not have any pre-existing ocular or demyelinating diseases suddenly experienced a loss of vision after SARS-CoV-2 infection. The patients expressed a central scotoma and a fever as the primary concern. The results of the fundus photography were found to be normal. However, the automated perimetry and MRI scans showed evidence of some typical signs. Out of the 15 patients diagnosed with ARON after SARS-CoV-2 infection, only one individual tested positive for the aquaporin-4 antibody. CONCLUSION: Direct viral invasion of the central nervous system and an immune-related process are the two primary causes of SARS-CoV-2-related ARON.

Symptom Clusters in Children With Leukemia Receiving Chemotherapy: A Scoping Review.

BACKGROUND: Leukemia represents the most prevalent childhood malignancy. Understanding the symptom clusters (SCs) associated with leukemia may help develop an effective care plan for affected children. OBJECTIVES: The aims of this study were to summarize the methods of identifying SCs; ascertain the types, attributes, and changing patterns of SCs during different chemotherapy phases; and provide a point of reference for the subsequent improvement of symptom management in pediatric leukemia. METHODS: The methodological framework employed was the Joanna Briggs Institute Scoping Review Guide. A comprehensive search was conducted across various databases, including PubMed, EMBASE, CINAHL, Web of Science, MEDLINE, Scopus, and China National Knowledge Infrastructure from inception until July 15, 2023. RESULTS: A total of 14 articles were included in this review, 6 in English and 8 in Chinese. The Memorial Symptom Assessment Scale 10-18 is the most commonly used instrument, whereas factor analysis is the most common statistical method for SC identification. The SCs were classified into 12 categories. The most severe SCs varied across different phases. Specifically, the emotional cluster dominated the prechemotherapy phase, the gastrointestinal cluster surfaced during postinduction therapy, and the consolidation and maintenance therapy phases revealed the self-image disorder cluster. CONCLUSION: Various consistent and dynamic SCs manifest among pediatric patients with leukemia undergoing chemotherapy. IMPLICATIONS FOR PRACTICE: Future research endeavors should formulate clear criteria to determine the stability and consistency of SCs, validate SC composition and characteristics, and devise precise symptom management protocols based on SC characteristics in the distinct chemotherapy phases.

[Cloning and functional characterization of the pinoresinol-lariciresinol reductase gene IiPLR2 in Isatis indigotica].

The pinoresinol-lariciresinol reductase (PLR), a crucial enzyme in the biosynthesis of lignans in plants, catalyzes a two-step reaction to produce lariciresinol and secoisolariciresinol. Lignans such as lariciresinol are the effective components of traditional Chinese medicine Radix Isatidis in exerting antiviral activity. In order to study the function of the key enzyme PLR in the biosynthesis of lariciresinol in Isatis indigotica, the original plant of Radix Isatidis, IiPLR2 was cloned from I. indigotica, with a full length of 954 bp, encoding 317 amino acids. Multiple sequence alignment showed that IiPLR2 contained a conserved nicotinamide adenine dinucleotide phosphate (NADPH)-binding motif. The phylogenetic tree showcased that IiPLR2 shared the same clade with AtPrR1 from Arabidopsis thaliana. The prokaryotic expression vector pET32a-IiPLR2 was constructed and then transformed into Escherichia coli BL21(DE3) competent cells for protein expression. The purified enzyme IiPLR2 could catalyze the conversion of pinoresinol to lariciresinol and the conversion of lariciresinol to secoisolariciresinol. The cloning, sequencing, and catalytic functional analysis of IiPLR2 in this study enrich the understanding of this kind of functional proteins in I. indigotica and supplement the biosynthesis pathways of lignans. Moreover, this study provides a functional module for further research on metabolic regulation and synthetic biology and lays a foundation for comprehensively revealing the relationship between the spatial structures and catalytic functions of such proteins.

The Synergistic Anti-tumor Effects of Evodiamine based on Animal Model Experiments: A Systematic Review and Meta-analysis.

BACKGROUND: Evodiamine (EVO) is an alkaloid extracted from the dried and nearly ripe fruits of Euodia rutaecarpa and used as an anti-cancer, anti-inflammatory and anti-obesity agent. However, robust evidence of preclinical experiments has been lacking so far. Therefore, the purpose of this article was to investigate the effect of EVO in combination with other treatments on tumors in animal experiments. METHODS: A systematic review and meta-analysis were conducted to assess the anti-tumor effect of evodiamine-combined therapy. The search engine and electronic databases included PubMed, Scopus, China Knowledge Resource Integrated Database (CNKI), and SinoMed. The research method was based on the PRISMA checklist. RESULTS: A total of 7 studies and 108 animals were included. As a result, EVO combined therapy was found to be more effective than EVO monotherapy. The SMD was -25.64(95% CI: -5.77 -3.13) in tumor growth. In tumor weight, the SMD was -8.91(95% CI: -16.37, -1.44). CONCLUSION: EVO has the potential to alleviate the toxicity of chemotherapeutic agents, which increases the translatability to the clinical situation.

The degree of population aging and carbon emissions: Analysis of mediation effect and multi-scenario simulation.

The continuous deepening of aging has posed new challenges for global sustainable development. Measuring the impact of population aging on carbon emissions is crucial for the next stage of climate governance. However, the structural changes in social production and consumption make it difficult to evaluate the impact effects. Therefore, this study constructed a bidirectional fixed Space Durbin Model to explore the mediating pathway of aging's impact on carbon emissions. Furthermore, we have established high-precision prediction models to simulate the evolution trajectory of carbon emissions under multi-factor driving scenarios. The main findings are as follows: (1) The process of carbon emission reduction due to population aging has significant energy hindrance effect and industrial structure effect, while the process of carbon growth is constrained by the consumption enhancement effect, technology progress effect and labor participation effect. (2) The moderating effects of energy consumption and technological innovation on carbon emissions under the aging process are 10.74% and 10.24%, respectively, while the moderating effects of industrial structure and labor force participation are relatively weak. (3) The goodness of fit of the MNGM-ARIMA and MNGM-BPNN models is over 97%. Carbon emissions in the high aging regions show a decreasing trend in all scenarios except the energy consumption-driven scenario, while in the medium and low aging regions decrease slowly only in the R&D- and labor supply-driven scenarios. This study advocates developing heterogeneous emission reduction measures based on the degree of aging, accelerating supply side upgrading, and increasing the proportion of green consumption.

Correction of Thin Cirrus Absorption Effects in Landsat 8 Thermal Infrared Sensor Images Using the Operational Land Imager Cirrus Band on the Same Satellite Platform.

Data from the Operational Land Imager (OLI) and the Thermal Infrared Sensor (TIRS) instruments onboard the Landsat 8 and Landsat 9 satellite platforms are subject to contamination by cloud cover, with cirrus contributions being the most difficult to detect and mask. To help address this issue, a cirrus detection channel (Band 9) centered within the 1.375-µm water vapor absorption region was implemented on OLI, with a spatial resolution of 30 m. However, this band has not yet been fully utilized in the Collection 2 Landsat 8/9 Level 2 surface temperature data products that are publicly released by U.S. Geological Survey (USGS). The temperature products are generated with a single-channel algorithm. During the surface temperature retrievals, the effects of absorption of infrared radiation originating from the warmer earth's surfaces by ice clouds, typically located in the upper portion of the troposphere and re-emitting at much lower temperatures (approximately 220 K), are not taken into consideration. Through an analysis of sample Level 1 TOA and Level 2 surface data products, we have found that thin cirrus cloud features present in the Level 1 1.375-µm band images are directly propagated down to the Level 2 surface data products. The surface temperature errors resulting from thin cirrus contamination can be 10 K or larger. Previously, we reported an empirical and effective technique for removing thin cirrus scattering effects in OLI images, making use of the correlations between the 1.375-µm band image and images of any other OLI bands located in the 0.4-2.5 µm solar spectral region. In this article, we describe a variation of this technique that can be applied to the thermal bands, using the correlations between the Level 1 1.375-µm band image and the 11-µm BT image for the effective removal of thin cirrus absorption effects. Our results from three data sets acquired over spatially uniform water surfaces and over non-uniform land/water boundary areas suggest that if the cirrus-removed TOA 11-µm band BT images are used for the retrieval of the Level 2 surface temperature (ST) data products, the errors resulting from thin cirrus contaminations in the products can be reduced to about 1 K for spatially diffused cirrus scenes.

Postoperative radiotherapy with docetaxel versus cisplatin for high-risk oral squamous cell carcinoma: a randomized phase II trial with exploratory analysis of ITGB1 as a potential predictive biomarker.

BACKGROUND: Oral squamous cell carcinoma (OSCC) causes significant mortality and morbidity worldwide. Surgical resection with adjuvant radiotherapy remains the standard treatment for locally advanced resectable OSCC. Results from landmark trials have established postoperative concurrent cisplatin-radiotherapy (Cis-RT) as the standard treatment for OSCC patients with high-risk pathologic features. However, cisplatin-related toxicity limits usage in clinical practice. Given the need for effective but less toxic alternatives, we previously conducted a single-arm trial showing favorable safety profiles and promising efficacy of concurrent docetaxel-radiotherapy (Doc-RT). METHODS: In this randomized phase 2 trial, we aimed to compare Doc-RT with the standard Cis-RT in postoperative OSCC patients. Eligible patients had AJCC stage III-IV resectable OSCC with high-risk pathologic features. Two hundred twenty-four patients were enrolled and randomly assigned to receive concurrent Doc-RT or Cis-RT. The primary endpoint was 2-year disease-free survival (DFS). Secondary endpoints included overall survival (OS), locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), and adverse events (AEs). Integrin ß1 (ITGB1) expression was analyzed as a biomarker for efficacy. RESULTS: After a median 28.8-month follow-up, 2-year DFS rates were 63.7% for Doc-RT arm and 56.1% for Cis-RT arm (p = 0.55). Meanwhile, Doc-RT demonstrated comparable efficacy to Cis-RT in OS, LRFS, and DMFS. Doc-RT resulted in fewer grade 3 or 4 hematological AEs. Low ITGB1 was associated with improved Doc-RT efficacy versus Cis-RT. CONCLUSIONS: This randomized trial directly compared Doc-RT with Cis-RT for high-risk postoperative OSCC patients, with comparable efficacy and less toxicity. ITGB1 merits further validation as a predictive biomarker to identify OSCC patients most likely to benefit from Doc-RT. Findings indicate docetaxel may be considered as a concurrent chemoradiation option in this setting. TRIAL REGISTRATION: www. CLINICALTRIALS: gov . NCT02923258 (date of registration: October 4, 2016).

Research progress on hepatotoxicity mechanism of polygonum multiflorum and its main components.

As a traditional tonic Chinese medicine, Polygonum multiflorum is widely used in clinical practice. However, with the deepening of modern pharmacological research, its drug toxicity, especially hepatotoxicity, has become increasingly prominent. Based on a large number of clinical and experimental evidence, it has been confirmed that Polygonum multiflorum and its main active ingredients such as anthraquinones and diphenylethylene glucoside can cause different degrees of hepatotoxicity. Further studies have shown that the toxicological mechanisms involved in the hepatotoxicity of different extracts and components of Polygonum multiflorum may include oxidative phosphorylation, bile acid excretion, different metabolic pathways, genetic and metabolic factors, immune homeostasis, etc. By sorting out and summarizing the literature related to hepatotoxicity of Polygonum multiflorum in recent years, this paper discussed the hepatotoxicity mechanism of Polygonum multiflorum and its main components and some contradictions in related reports.

Radiofrequency enhances drug release from responsive nanoflowers for hepatocellular carcinoma therapy.

Hepatocellular carcinoma (HCC) is the sixth most common malignant tumor and the third leading cause of cancer death worldwide. Most patients are diagnosed at an advanced stage, and systemic chemotherapy is the preferred treatment modality for advanced HCC. Curcumin (CUR) is a polyphenolic antineoplastic drug with low toxicity obtained from plants. However, its low bioavailability and poor solubility limit its functionality. In this study, radiofrequency- (RF) enhanced responsive nanoflowers (NFs), containing superparamagnetic ferric oxide nanoclusters (Fe3O4 NCs), - CUR layer, - and MnO2 (CUR-Fe@MnO2 NFs), were verified to have a thermal therapeutic effect. Transmission electron microscopy was used to characterize the CUR-Fe@MnO2 NFs, which appeared flower-like with a size of 96.27 nm. The in vitro experimental data showed that RF enhanced the degradation of CUR-Fe@MnO2 NFs to release Mn2+ and CUR. The cytotoxicity test results indicated that after RF heating, the CUR-Fe@MnO2 NFs significantly suppressed HCC cell proliferation. Moreover, CUR-Fe@MnO2 NFs were effective T 1/T 2 contrast agents for molecular magnetic resonance imaging due to the release of Mn2+ and Fe3O4 NCs.

Enhancing the Photosensitivity of Hypocrellin A by Perylene Diimide Metallacage-Based Host-Guest Complexation for Photodynamic Therapy.

The development of supramolecular hosts which can efficiently encapsulate photosensitizers to improve the photodynamic efficacy holds great promise for cancer therapy. Here, we report two perylene diimide-based metallacages that can form stable host-guest complexes with planar conjugated molecules including polycyclic aromatic hydrocarbons and photosensitizers (hypocrellin A). Such host-guest complexation not only prevents the aggregation of photosensitizers in aqueous environments, but also offers fluorescence resonance energy transfer (FRET) from the metallacage to the photosensitizers to further improve the singlet oxygen generation (ΦΔ = 0.66). The complexes are further assembled with amphiphilic polymers, forming nanoparticles with improved stability for anticancer study. Both in vitro and in vivo studies indicate that the nanoparticles display excellent anticancer activities upon light irradiation, showing great potential for cancer photodynamic therapy. This study provides a straightforward and effective approach for enhancing the photosensitivity of conventional photosensitizers via host-guest complexation-based FRET, which will open a new avenue for host-guest chemistry-based supramolecular theranostics.

Stellate Ganglion Block Attenuates LPS-Induced Acute Lung Injury by Activating Sirt3 Regulation of Oxidative Stress and Inflammation.

Stellate ganglion blocks (SGBs) has been applied in clinics to alleviate pain-related syndromes for almost a century. In recent years, it has been reported that SGB can attenuate acute lung injury (ALI) in animals. However, the details of these molecular mechanisms remain complex and unclear. In this study, rats were randomly divided into four groups: group C (receiving no treatment), group NS (receiving the intratracheal instillation of normal saline), group L (receiving the intratracheal instillation of LPS) and group LS (receiving SGB after the intratracheal instillation of LPS). The pathological damage of lung tissue, arterial blood gases, the differentiation of alveolar macrophages (AMs) and inflammatory cytokines (IL-1ß, IL-6, IL-10) were detected. Furthermore, the oxidative stress indexes (ROS, CYP-D, T-SOD, Mn-SOD and CAT) in serum and the levels of Sirt3 signaling-associated proteins (JAK2/STAT3, NF-κb p65, CIRP and NLRP3) in the lungs were measured. The results revealed that SGB could attenuate lung tissue damage, improve pulmonary oxygenation, promote the differentiation of AMs to the M2 phenotype, decrease the secretion of IL-1ß and IL-6, and increase the secretion of IL-10. Meanwhile, SGB was found to inhibit the production of ROS and CYP-D, and enhance the activities of T-SOD, Mn-SOD and CAT. Furthermore, SGB upregulated Sirt3 and downregulated JAK2/STAT3 and NF-κb p65 phosphorylation, CIRP and NLRP3. Our work revealed that SGB could attenuate LPS-induced ALI by activating the Sirt3-mediated regulation of oxidative stress and pulmonary inflammation; this may shed new light upon the protection of SGB and provide a novel prophylactic strategy for LPS-induced ALI.

Investigation of the role of distances from liquid crystal monomer (LCM) factories on distribution of LCMs in surface soil samples.

Liquid crystal monomers (LCMs), which are commonly used in electronic device screens, have attracted attention as a potential class of emerging organic pollutants with persistent, bioaccumulative, and toxic (PBT) properties. This study involved the collection of 54 surface soil samples around one LC industrial park at increasing spatial distances within 1 km, 1-3 km, and 3-5 km from the center of the LC industrial park. Our observations revealed the presence of LCMs in 46 of 54 surface soil samples examined. Of the 39 target LCMs, 36 were identified, comprising 14 non-fluorinated and 22 fluorinated LCMs. Nine LCMs were detected at frequencies exceeding 20%, with 3bcHdFB exhibiting the highest detection frequency of 59% in the soil samples. The total LCM concentrations across the 46 sampling locations varied from 0.0072 to 17.24 ng/g dw, with the highest total concentrations at sampling sites within 1 km of the liquid crystal plant, suggesting that manufacturing processes may be a potential source for LCM release into the environment. Differences were observed in the LCM contamination patterns among the three sampling areas. Additionally, we observed a decrease in the median LCM concentration with increasing distance from the center of the LC industrial park. However, no statistically significant differences (p > 0.05) in LCM concentrations were observed across the three distances assessed in this study. This may be owing to the limited variety of target compounds analyzed and the limited number of soil samples. Our results emphasize that further studies on the emissions and pollution characteristics of LCMs during production are warranted.

Association Between Pornography Use, Sexism, and Sexual Violence Myth Acceptance in Chinese Men: The Moderating Effect of Perceived Realism.

Pornography is spreading more and more widely due to websites, applications, and social media. It has attracted the attention of a large number of researchers who are sometimes divided on the impact of pornography. However, the relationship between pornography and sexual violence myths has received little scholarly attention in China. Based on the 3AM model and previous research, the study examined hostile sexism (HS) as a mediator and perceived realism as a moderator in the links between pornography use frequency and sexual violence myths in a sample of Chinese men (N = 376). The results showed that although pornography use and sexual violence myths did not directly correlate with one another, there was an indirect correlation through HS. Further, perceived realism moderated the relationship between pornography use frequency and HS. When participants' perceived realism was high (i.e. +1 SD), the indirect effect of HS was strong; when participants' perceived realism was low (i.e. -1 SD), the indirect effect of HS was not significant. Taken together, the findings reveal the cross-cultural consistency of the 3AM theory in China, and the findings provide new insight into the potential impact of pornography on sexism. At the same time, the results suggest an increase in appropriate education and interventions to reduce the incidence of sexual violence.

A Method for Detecting Five Carbapenemases in Bacteria Based on CRISPR-Cas12a Multiple RPA Rapid Detection Technology.

Introduction: As the last line of defense for clinical treatment, Carbapenem antibiotics are increasingly challenged by multi-drug resistant bacteria containing carbapenemases. The rapid spread of these multidrug-resistant bacteria is the greatest threat to severe global health problems. Methods: To solve the problem of rapid transmission of this multidrug-resistant bacteria, we have developed a rapid detection technology using CRPSPR-Cas12a gene editing based on multiple Recombinase polymerase amplification. This technical method can directly isolate the genes of carbapenemase-containing bacteria from samples, with a relatively short detection time of 30 minutes. The instrument used for the detection is relatively inexpensive. Only a water bath can complete the entire experiment of Recombinase polymerase amplification and trans cleavage. This reaction requires no lid during the entire process while reducing a large amount of aerosol pollution. Results: The detection sensitivity of this method is 1.5 CFU/mL, and the specificity is 100%. Discussion: This multi-scene detection method is suitable for screening populations in wild low-resource environments and large-scale indoor crowds. It can be widely used in hospital infection control and prevention and to provide theoretical insights for clinical diagnosis and treatment.

High Expression of KIFC1 in Glioma Correlates with Poor Prognosis.

OBJECTIVE: Kinesin family member C1 (KIFC1), a non-essential kinesin-like motor protein, has been found to serve a crucial role in supernumerary centrosome clustering and the progression of several human cancer types. However, the role of KIFC1 in glioma has been rarely reported. Thus, the present study aimed to investigate the role of KIFC1 in glioma progression. METHODS: Online bioinformatics analysis was performed to determine the association between KIFC1 expression and clinical outcomes in glioma. Immunohistochemical staining was conducted to analyze the expression levels of KIFC1 in glioma and normal brain tissues. Furthermore, KIFC1 expression was knocked in the glioma cell lines, U251 and U87MG, and the functional roles of KIFC1 in cell proliferation, invasion and migration were analyzed using cell multiplication, wound healing and Transwell invasion assays, respectively. The autophagic flux and expression levels matrix metalloproteinase-2 (MMP2) were also determined using imaging flow cytometry, western blotting and a gelation zymography assay. RESULTS: The results revealed that KIFC1 expression levels were significantly upregulated in glioma tissues compared with normal brain tissues, and the expression levels were positively associated with tumor grade. Patients with glioma with low KIFC1 expression levels had a more favorable prognosis compared with patients with high KIFC1 expression levels. In vitro, KIFC1 knockdown not only inhibited the proliferation, migration and invasion of glioma cells, but also increased the autophagic flux and downregulated the expression levels of MMP2. CONCLUSION: Upregulation of KIFC1 expression may promote glioma progression and KIFC1 may serve as a potential prognostic biomarker and possible therapeutic target for glioma.

Efficacy and safety of trifluridine/tipiracil plus bevacizumab versus trifluridine/tipiracil monotherapy for refractory metastatic colorectal cancer: a retrospective cohort study.

Background: Several studies demonstrated trifluridine/tipiracil (TAS-102) plus bevacizumab (BEV) had better efficacy than the monotherapy of TAS-102 in refractory metastatic colorectal cancer (mCRC). However, it remains unclear whether Chinese population can benefit from this combination or not. Hence, we conducted this retrospective cohort study to compare the efficacy and safety between TAS-102 plus BEV with TAS-102 monotherapy in refractory mCRC. Methods: This retrospective cohort study enrolled patients (any age) with refractory mCRC from Hunan Cancer Hospital. The main inclusion criteria were histopathologically and/or radiographically confirmed refractory mCRC, World Health Organization (WHO) performance status of 0 to 2, adequate organ function, and initial treatment of TAS-102 with or without BEV between November 2020 and October 2022. Previous therapy with fruquintinib or regorafenib was allowed but not mandatory. Baseline demographic and clinical characteristics were collected appropriately. Every 2 or 3 treatment cycles, the patients were assessed by computed tomography (CT) scans and clinical assessments until disease progression or loss to follow-up. The National Cancer Institute Common Terminology Criteria for Adverse Events 5.0 (NCI-CTCAE 5.0) were presented as n (%). The primary endpoint was investigator-evaluated overall survival (OS). As this is a retrospective cohort study, sample size calculation was not performed. Eligible patients would be enrolled as many as possible. Results: A total of 90 patients were enrolled, including 58 patients who received TAS-102 plus BEV and another 32 patients who received TAS-102 monotherapy. The known baseline characteristics were comparable (P<0.05). With a median follow-up of 4.60 months (range, 0.20-22.80), the median OS (mOS) time in the TAS-102 plus BEV group was longer than that in the TAS-102 monotherapy group (10.83 vs. 7.43 months), but the difference was not significant (P=0.79). The median progression-free survival (mPFS) time was comparable between the two groups (4.67 vs. 4.30 months, P=0.96). Multivariate Cox regression analysis demonstrated that undergoing therapy after TAS-102 either with or without BEV was an independent risk factor for OS [hazard ratio (HR) =0.25; 95% confidence interval (CI): 0.09-0.71, P<0.01], and previous treatment with cetuximab was an independent protective factor for PFS (HR =0.17; 95% CI: 0.03-0.91, P=0.04). Of the 70 patients who were evaluated, those receiving TAS-102 plus BEV showed trend of a higher objective response rate (ORR) and disease control rate (DCR) than those who received TAS-102 monotherapy (P=0.16 and P=0.29, respectively). Adverse events (AEs) were similar between the two groups, except that the incidence of platelet count decrease (grade ≥3) was significantly higher in the TAS-102 plus BEV group. Conclusions: There was a trend in favor of the combination of BEV plus TAS-102 regarding OS and DCR, without reaching statistical significance, and it means that there was no clear advantage of one over the other in terms of efficacy. Further prospective studies are still necessary to draw a definite conclusion.

Efficacy of Raw Corn Starch in Insulinoma-Related Hypoglycemia: A Promising Supportive Therapy.

Objective To investigate the efficacy of raw corn starch (RCS) in clinical management of insulinoma-induced hypoglycemia. Methods We retrospectively collected clinical data of insulinoma patients who received RCS-supplemented diet preoperatively, and analyzed the therapeutic effects of the RCS intervention on blood glucose control, weight change, and its adverse events. Results The study population consisted of 24 cases of insulinoma patients, 7 males and 17 females, aged 46.08±14.15 years. Before RCS-supplemented diet, all patients had frequent hypoglycemic episodes (2.51±3.88 times/week), concurrent with neuroglycopenia (in 83.3% of patients) and autonomic manifestations (in 75.0% of patients), with the median fasting blood glucose (FBG) of 2.70 (interquartile range [IQR]: 2.50-2.90) mmol/L. The patients' weight increased by 0.38 (IQR: 0.05-0.65) kg per month, with 8 (33.3%) cases developing overweight and 7 (29.2%) cases developing obesity. All patients maintained the RCS-supplemented diet until they underwent tumor resection (23 cases) and transarterial chemoembolization for liver metastases (1 case). For 19 patients receiving RCS throughout the day, the median FBG within one week of nutritional management was 4.30 (IQR: 3.30-5.70) mmol/L, which was a significant increase compared to pre-nutritional level [2.25 (IQR: 1.60-2.90) mmol/L; P < 0.001]. Of them, 10 patients receiving RCS throughout the day for over four weeks had sustained improvement in FBG compared to pre-treatment [3.20 (IQR: 2.60-3.95) mmol/L vs. 2.15 (IQR: 1.83-2.33) mmol/L; P < 0.001). Five patients who received RCS only at night also had a significant increase in FBG within one week of nutritional management [3.50 (IQR: 2.50-3.65) mmol/L vs. 2.20 (IQR:1.80-2.60) mmol/L; P < 0.001], but only one patient who continued to receive RCS for over four weeks did not have a significant improvement in FBG. No improvement in weight gain was observed upon RCS supplementation. Mild diarrhea (2 cases) and flatulence (1 case) occurred, and were relieved by reduction of RCS dose. Conclusion The RCS-supplemented diet is effective in controlling insulinoma-induced hypoglycemia.