Predicting the global potential distribution of Bursaphelenchus xylophilus using an ecological niche model: expansion trend and the main driving factors.

Bursaphelenchus xylophilus (Steiner&Buhrer) Nickle is a global quarantine pest that causes devastating mortality in pine species. The rapid and uncontrollable parasitic spread of this organism results in substantial economic losses to pine forests annually. In this study, we used the MaxEnt model and GIS software ArcGIS10.8 to predict the distribution of B. xylophilus based on collected distribution points and 19 environmental variables (with a correlation coefficient of|R| > 0.8) for the contemporary period (1970-2000), 2041-2060 (2050s), 2061-2080 (2070s), and 2081-2100 (2090s) under four shared socioeconomic pathways (SSPs). We conducted a comprehensive analysis of the key environmental factors affecting the geographical distribution of B. xylophilus and suitable distribution areas. Our results indicate that in current prediction maps B. xylophilus had potential suitable habitats in all continents except Antarctica, with East Asia being the region with the most highly suitable areas and the most serious epidemic area currently. Precipitation of the warmest quarter, temperature seasonality, precipitation of the wettest month, and maximum temperature of the warmest month were identified as key environmental variables that determine the distribution of B. xylophilus. Under future climatic conditions, the potential geographic distribution of B. xylophilus will expand relative to current conditions. In particular, under the SSP5-8.5 scenario in 2081-2100, suitable areas will expand to higher latitudes, and there will be significant changes in suitable areas in Europe, East Asia, and North America. These findings are crucial for future prevention and control management and monitoring.

Integrated transcriptomic and WGCNA analyses reveal candidate genes regulating mainly flavonoid biosynthesis in Litsea coreana var. sinensis.

Litsea coreana Levl. var. sinensis (Allen) Yang et P. H. Huang is a popular ethnic herb and beverage plant known for its high flavonoid content, which has been linked to a variety of pharmacological benefits and crucial health-promoting impacts in humans. The progress in understanding the molecular mechanisms of flavonoid accumulation in this plant has been hindered due to the deficiency of genomic and transcriptomic resources. We utilized a combination of Illumina and Oxford Nanopore Technology (ONT) sequencing to generate a de novo hybrid transcriptome assembly. In total, 126,977 unigenes were characterized, out of which 107,977 were successfully annotated in seven public databases. Within the annotated unigenes, 3,781 were categorized into 58 transcription factor families. Furthermore, we investigated the presence of four valuable flavonoids-quercetin-3-O-ß-D-galactoside, quercetin-3-O-ß-D-glucoside, kaempferol-3-O-ß-D-galactoside, and kaempferol-3-O-ß-D-glucoside in 98 samples, using high-performance liquid chromatography. A weighted gene co-expression network analysis identified two co-expression modules, MEpink and MEturquoise, that showed strong positive correlation with flavonoid content. Within these modules, four transcription factor genes (R2R3-MYB, NAC, WD40, and ARF) and four key enzyme-encoding genes (CHI, F3H, PAL, and C4H) emerged as potential hub genes. Among them, the R2R3-MYB (LcsMYB123) as a homologous gene to AtMYB123/TT2, was speculated to play a significant role in flavonol biosynthesis based on phylogenetic analysis. Our findings provided a theoretical foundation for further research into the molecular mechanisms of flavonoid biosynthesis. Additionally, The hybrid transcriptome sequences will serve as a valuable molecular resource for the transcriptional annotation of L. coreana var. sinensis, which will contribute to the improvement of high-flavonoid materials.

NAC transcription factor SlNOR-like1 plays a dual regulatory role in tomato fruit cuticle formation.

The plant cuticle is an important protective barrier on the plant surface, constructed mainly by polymerized cutin matrix and a complex wax mixture. Although the pathway of plant cuticle biosynthesis has been clarified, knowledge of the transcriptional regulation network underlying fruit cuticle formation remains limited. In the present work, we discovered that tomato fruits of the NAC transcription factor SlNOR-like1 knockout mutants (nor-like1) produced by CRISPR/Cas9 [clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9] displayed reduced cutin deposition and cuticle thickness, with a microcracking phenotype, while wax accumulation was promoted. Further research revealed that SlNOR-like1 promotes cutin deposition by binding to the promoters of glycerol-3-phosphate acyltransferase6 (SlGPAT6; a key gene for cutin monomer formation) and CUTIN DEFICIENT2 (SlCD2; a positive regulator of cutin production) to activate their expression. Meanwhile, SlNOR-like1 inhibits wax accumulation, acting as a transcriptional repressor by targeting wax biosynthesis, and transport-related genes 3-ketoacyl-CoA synthase1 (SlKCS1), ECERIFERUM 1-2 (SlCER1-2), SlWAX2, and glycosylphosphatidylinositol-anchored lipid transfer protein 1-like (SlLTPG1-like). In conclusion, SlNOR-like1 executes a dual regulatory effect on tomato fruit cuticle development. Our results provide a new model for the transcriptional regulation of fruit cuticle formation.

Application effect of diversified health-promoting models on rehabilitation exercises for cervical spondylotic myelopathy.

BACKGROUND: With improving living standards, the incidence of cervical spondylotic myelopathy (CSM) has become increasingly high. OBJECTIVE: The study aims to explore the effect of diversified health-promoting models on rehabilitation exercises in patients with CSM after an operation. METHOD: This was a randomized controlled trial, wherein 107 patients with CSM treated by neurosurgery were selected as the subjects. Of those, 52 patients in the control group adopted the conventional health-promoting model, while the remaining 55 patients in the intervention group adopted diversified health-promoting models. The effect of rehabilitation exercises in the two groups was evaluated according to the self-efficacy rehabilitation outcome scale, grip strength measurement of the affected limb, and Barthel index. RESULTS: At Day 3 post-operation and before discharge, the self-efficacy management of rehabilitation exercises in the intervention group was better than that of the control group (P< 0.05). The grip strength measurement of the affected limb, Japanese Orthopedic Association score of the cervical vertebra, and Barthel index of the two groups at Day 3 post-operation were lower than before the intervention and were not statistically significant (P> 0.05). However, these three items before discharge were improved when compared with those of before intervention and were statistically significant (P< 0.05). CONCLUSION: Postoperative rehabilitation exercises guided by the diversified health-promoting models for patients with CSM can improve the patients' self-efficacy management ability in rehabilitation exercises, help improve grip strength, and promote the recovery of cervical vertebra function, thereby improving the patients' quality of life.

Impact of perioperative enhanced recovery after surgery on wound infection in patients undergoing orthopaedic surgery: A meta-analysis.

The aim of this study was to evaluate the effects of perioperative application of enhanced recovery after surgery (ERAS) concepts on wound infections and post-operative complications in patients receiving orthopaedic surgery, to provide a theoretical basis for post-operative care. Randomised controlled trials (RCTs) on the application of ERAS to patients receiving orthopaedic surgery, published up to October 2023, were identified in PubMed, Web of Science, Cochrane Library, Embase, Wanfang, China Biomedical Literature Database and China National Knowledge Infrastructure databases. Literature was screened and evaluated by two reviewers based on the inclusion and exclusion criteria, and data were extracted from the final included articles. Data were analysed using RevMan 5.4 software. A total of 20 RCTs were included in the analysis, which included 1875 patients undergoing orthopaedic surgery, of whom 938 and 937 were in the ERAS and control groups, respectively. The analysis revealed that in patients undergoing orthopaedic surgery, implementation of ERAS in the perioperative period was associated with a significantly reduced the rate of wound infections (1.6% vs. 6.19%, risk ratio [RR]: 0.30, 95% confidence interval [CI]: 0.18-0.50, p < 0.001) and complication (5.12% vs. 21.88%, RR: 0.23, 95% CI: 0.17-0.32, p < 0.001) and can effectively shorten the hospital length of stay (standardised mean difference [SMD]: -2.50 days, 95% CI: -3.17 to -1.83 days, p < 0.001) compared with that of conventional care. The available evidence suggests that the implementation of ERAS in the perioperative period of patients undergoing orthopaedic surgery could effectively reduce the rate of wound infections and complications, shorten the hospital length of stay and promote the early recovery of patients.

Effect of humanised care on the surgical site wound infection after caesarean: A meta-analysis.

Herein, a meta-analysis was conducted to systematically evaluate the effect of humanised care on maternal postoperative wound infections in patients who underwent caesarean section. A computerised search of Embase, Cochrane Library, PubMed, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database and Wanfang database was performed, supplemented by a manual search from database inception to September 2023, to collate randomised controlled trials (RCTs) regarding the application of humanised care during the perioperative period of caesarean section. Two researchers screened and selected studies identified according to inclusion and exclusion criteria, and the included literature was evaluated for quality, extracted information and required data. Data analysis was performed using RevMan 5.4 software. Twenty RCTs comprising 2408 patients were included. The results revealed the humanised care group had a lower incidence of postoperative wound infections (0.83% vs. 4.32%, odds ratio [OR]: 0.26, 95% confidence interval [CI]: 0.15-0.46, p < 0.00001) and fewer postoperative complications than the conventional care group (4.32% vs. 16.35%, OR: 0.23, 95% CI: 0.16-0.31, p < 0.00001), with lower anxiety scores (standardised mean difference [SMD]: -3.15, 95% CI: -3.90 to -2.40, p < 0.00001) and depression scores (SMD: -3.68, 95% CI: -4.49 to -2.88, p < 0.00001). The application of humanised care during the perioperative period of caesarean section can prevent postoperative wound infection, reduce postoperative complications and help alleviate maternal anxiety and depression, which is worthy of clinical promotion and application.

Long-Term Imaging of Cys in Cells and Tumor Mice by a Solid-State Fluorescence Probe.

Cysteine is an important biological thiol and is closely related to cancer. It remains a challenge to develop a probe that can provide long-term fluorescence detection and imaging of Cys in cells as well as in living organisms. Here, a solid-state fluorophore HTPQ is combined with an acrylate group to construct a solid-state fluorescent probe HTPQC for Cys recognition. The fluorescence of the probe is quenched when the photoinduced electron transfer (PET) process is turned on and the excited-state intramolecular proton transfer (ESIPT) process is turned off. In the presence of Cys, an obvious solid-state fluorescence signal can be observed. The double quenching mechanism makes the probe HTPQC have the advantages of high sensitivity, good selectivity, and high contrast of biological imaging. Due to low cytotoxicity, the probe HTPQC can be used to detect exogenous and endogenous Cys in living cells and is capable of imaging over long periods of time. By making full use of long wavelengths, the probe can be applied for the detection of Cys levels in tumor mice and equipped with the ability to conduct long-term imaging in vivo.

Enhanced Sensing Mechanism Based on Shifting an Exceptional Point.

Non-Hermitian systems associated with exceptional points (EPs) are expected to demonstrate a giant response enhancement for various sensors. The widely investigated enhancement mechanism based on diverging from an EP should destroy the EP and further limits its applications for multiple sensing scenarios in a time sequence. To break the above limit, here, we proposed a new enhanced sensing mechanism based on shifting an EP. Different from the mechanism of diverging from an EP, our scheme is an EP nondemolition and the giant enhancement of response is acquired by a slight shift of the EP along the parameter axis induced by perturbation. The new sensing mechanism can promise the most effective response enhancement for all sensors in the case of multiple sensing in a time sequence. To verify our sensing mechanism, we construct a mass sensor and a gyroscope with concrete physical implementations. Our work will deepen the understanding of EP-based sensing and inspire designing various high-sensitivity sensors in different physical systems.

Analysis of Factors Correlated with Postoperative Kinesiophobia in Patients with Cervical Spondylotic Myelopathy: A Cross-Sectional Survey.

Objective: To investigate the prevalence of postoperative kinesiophobia in patients with cervical spondylotic myelopathy (CSM) and factors influencing the occurrence of kinesiophobia, to provide relevant basis for making clinical decisions for targeted interventions. Methods: We enrolled a total of 85 patients who underwent CSM surgery at two grade-A general public hospitals in Fujian Province between September 2021 and May 2022. We conducted a questionnaire survey using the Tampa Scale for Kinesiophobia (TSK) and the Zung Self-Rating Anxiety Scale (SAS). Patients evaluated pain using a visual analogue scale. We used one-way ANOVA and logistic multiple regression analysis to identify the relevant influencing factors. Results: The TSK score was (41.88±4.46) in 85 postoperative CSM patients, 65 males and 20 females, and there were 31 patients under 40 years old, 54 patients over 40 years old, 58 patients below high school education and 27 patients above high school education, and among them, 81.17% were diagnosed with kinesiophobia. Age was positively correlated with TSK score (r = 0.379, P < 0.05) and therefore a risk factor for kinesiophobia (OR = 1.941, 95% CI = 1.021-3.690). Additionally, the duration of the disease was a protective factor for kinesiophobia (OR = 0.179, 95% CI = 0.053-0.605). Conclusion: Patients with CSM were at high risk of developing kinesiophobia postoperatively. Age and duration of the disease were factors influencing the occurrence of kinesiophobia in this group.

Iron Deficiency Modulates Metabolic Landscape of Bacteroidetes Promoting Its Resilience during Inflammation.

Bacteria have to persist under low iron conditions in order to adapt to the nutritional immunity of a host. Since the knowledge of iron stimulon of Bacteroidetes is sparse, we examined oral (Porphyromonas gingivalis and Prevotella intermedia) and gut (Bacteroides thataiotaomicron) representatives for their ability to adapt to iron deplete and iron replete conditions. Our transcriptomics and comparative genomics analysis show that many iron-regulated mechanisms are conserved within the phylum. They include genes upregulated in low iron, as follows: fldA (flavodoxin), hmu (hemin uptake operon), and loci encoding ABC transporters. Downregulated genes were frd (ferredoxin), rbr (rubrerythrin), sdh (succinate dehydrogenase/fumarate reductase), vor (oxoglutarate oxidoreductase/dehydrogenase), and pfor (pyruvate:ferredoxin/flavodoxin oxidoreductase). Some genus-specific mechanisms, such as the sus of B. thetaiotaomicron coding for carbohydrate metabolism and the xusABC coding for xenosiderophore utilization were also identified. While all bacteria tested in our study had the nrfAH operon coding for nitrite reduction and were able to reduce nitrite levels present in culture media, the expression of the operon was iron dependent only in B. thetaiotaomicron. It is noteworthy that we identified a significant overlap between regulated genes found in our study and the B. thetaiotaomicron colitis study (W. Zhu, M. G. Winter, L. Spiga, E. R. Hughes et al., Cell Host Microbe 27:376-388, 2020, http://dx.doi.org/10.1016/j.chom.2020.01.010). Many of those commonly regulated genes were also iron regulated in the oral bacterial genera. Overall, this work points to iron being the master regulator enabling bacterial persistence in the host and paves the way for a more generalized investigation of the molecular mechanisms of iron homeostasis in Bacteroidetes. IMPORTANCE Bacteroidetes are an important group of anaerobic bacteria abundant both in the oral and gut microbiomes. Although iron is a required nutrient for most living organisms, the molecular mechanisms of adaptation to the changing levels of iron are not well known in this group of bacteria. We defined the iron stimulon of Bacteroidetes by examination of the transcriptomic response of Porphyromonas gingivalis and Prevotella intermedia (both belong to the oral microbiome) and Bacteroidetes thetaiotaomicron (belongs to the gut microbiome). Our results indicate that many of the iron-regulated operons are shared among the three genera. Furthermore, using bioinformatics analysis, we identified a significant overlap between our in vitro studies and transcriptomic data derived from a colitis study, thus underscoring the biological significance of our work. Defining the iron-dependent stimulon of Bacteroidetes can help to identify the molecular mechanisms of iron-dependent regulation as well as better understand the persistence of the anaerobes in the human host.

Tenofovir alters the immune microenvironment of pregnant women with hepatitis B virus infection: Evidence from single-cell RNA sequencing.

BACKGROUND: Mother-to-child is the main route of the transmission of hepatitis B virus (HBV) infection. Tenofovir fumarate (TDF) antiviral treatment has become the most extensive choice worldwide. However, the effects of TDF treatment on the immune function of pregnant women remains unclear. Here we investigate the effect of TDF treatment on the immune microenvironment of pregnant women with HBV infection using single-cell RNA sequencing (scRNA-seq). METHODS: Three HBV-infected pregnant women were treated with TDF and six samples were collected before and after the treatment. In total, 68,200 peripheral blood mononuclear cells (PBMCs) were extracted for 10 × scRNA-seq. The cells were clustered using t-distributed stochastic neighbor embedding (t-SNE) and unbiased computational informatics analysis. RESULTS: The analysis identified four-cell subtypes, including T cells, monocytes, natural killer (NK) cells, and B cells, and unraveled the developmental trajectory and maturation of CD4+ T and CD8+ T cell subtypes. The cellular state and molecular features of the effector/memory T cells revealed a significant increase in the inflammatory state of CD4+ T cells and the cytotoxic characteristics of CD8+ T cells. Additionally, after TDF treatment, the monocytes showed a tendency for M1 polarization, and the cytotoxicity of NK cells was enhanced. Furthermore, the analysis of intercellular communication revealed the interaction of various subtypes of cells and the heterogeneous expression of key signal pathways. CONCLUSIONS: The findings of this study reveal significant differences in cellular subtypes and molecular characteristics of PBMCs of pregnant women with HBV infection before and after TDF treatment and demonstrate the recovery of immune response after treatment. These findings could help develop immune intervention measures to control HBV during pregnancy and the puerperium period.

Large-scale genetic characterization of the model sulfate-reducing bacterium, Desulfovibrio vulgaris Hildenborough.

Sulfate-reducing bacteria (SRB) are obligate anaerobes that can couple their growth to the reduction of sulfate. Despite the importance of SRB to global nutrient cycles and their damage to the petroleum industry, our molecular understanding of their physiology remains limited. To systematically provide new insights into SRB biology, we generated a randomly barcoded transposon mutant library in the model SRB Desulfovibrio vulgaris Hildenborough (DvH) and used this genome-wide resource to assay the importance of its genes under a range of metabolic and stress conditions. In addition to defining the essential gene set of DvH, we identified a conditional phenotype for 1,137 non-essential genes. Through examination of these conditional phenotypes, we were able to make a number of novel insights into our molecular understanding of DvH, including how this bacterium synthesizes vitamins. For example, we identified DVU0867 as an atypical L-aspartate decarboxylase required for the synthesis of pantothenic acid, provided the first experimental evidence that biotin synthesis in DvH occurs via a specialized acyl carrier protein and without methyl esters, and demonstrated that the uncharacterized dehydrogenase DVU0826:DVU0827 is necessary for the synthesis of pyridoxal phosphate. In addition, we used the mutant fitness data to identify genes involved in the assimilation of diverse nitrogen sources and gained insights into the mechanism of inhibition of chlorate and molybdate. Our large-scale fitness dataset and RB-TnSeq mutant library are community-wide resources that can be used to generate further testable hypotheses into the gene functions of this environmentally and industrially important group of bacteria.

Effect of Bacillus amyloliquefaciens LSG2-8 on the intestinal barrier function of Amur minnow (Rhynchocypris lagowskii).

Probiotics are widely used in aquaculture. This article aims to study the effect of Bacillus amyloliquefaciens LSG2-8 on the intestinal barrier function of Rhynchocypris lagowskii. B. amyloliquefaciens LSG2-8 were added to R. lagowskii basal diets (CK) as additives at four concentrations: 1.0 × 106 (D-6), 1.0 × 107 (D-7), 1.0 × 108 (D-8) and 1.0 × 109 (D-9) CFU g-1 by dry weight of basal diet. After a 56-day feeding experiment, the activities of intestinal digestive enzymes and immunity-related enzymes of R. lagowskii on group D-6, D-7, D-8 and D-9 diet were significantly higher than the control (P < 0.05). In molecular experiments, the authors found that the levels of TGF-ß mRNA, IL-10 mRNA, ZO-1 mRNA and claudin-3 mRNA in group D-8 R. lagowskii were significantly higher (P < 0.05) than those of the control and other groups. Furthermore, the levels of IL-1ß and IL-8 mRNA of R. lagowskii on group D-6, D-7, D-8 and D-9 diet were significantly lower than those of the control (P < 0.05). In addition, the authors found that B. amyloliquefaciens LSG2-8 can regulate the intestinal flora balance and improve the intestinal structure of R. lagowskii. In conclusion, B. amyloliquefaciens LSG2-8 can improve the intestinal barrier function of R. lagowskii and can be used as a feed additive in aquaculture.

Elucidation of Non-Intentionally Added Substances from Plant Fiber/Plastic Composites by UPLC-QTOF/MS.

Plant fiber/plastic composites (PPCs) have been widely used in food contact materials (FCMs) for many benefits, such as their claimed better environmental footprint compared to conventional plastics. However, their safety is still not fully understood and must be comprehensively evaluated. Non-volatiles extracted from six PPCs with different plant fibers and polymer matrices were characterized by employing ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry in combination with various spectral libraries and manual elucidation, taking into account spectral similarity and characteristic product ions. A total of 115 compounds were tentatively identified, 50 of which were oligomers or their derivatives from the sample with polylactic acid (PLA) and polybutylene adipate terephthalate (PBAT) as the polymer matrix, and some of them were Cramer rules class III substances based on the threshold of toxicological concern (TTC). Seven reaction products between PLA and PBAT monomers, as well as four derivatives of melamine, were elucidated and well detailed for the first time. In addition, bisphenol S was detected in all samples even though its origin remains to be further explored. Isoprothiolane, as an insecticide and fungicide used to control a range of rice pests, was identified in the sample with rice husk as fillers, experimentally confirming the presence of agrochemicals in samples containing plant fibers.

[Vitamins and Immune System Health].

Keeping the immune system healthy forms an effective way to fight infections. Past experience has shown that, in addition to effective interventions including vaccination, drug therapy, and non-pharmaceutical intervention (NPI), dietary nutrition and mental health are also key factors in maintaining immune system health and combating emerging and sudden outbreaks of infections. As the main dietary nutrients, vitamins are active regulators of the immune response and exert a critical impact on the immunity of the human body. Vitamin deficiency causes increased levels of inflammation and decreased immunity, which usually starts in the oral tissues. Appropriate vitamin supplementation can help the body optimize immune function, enhance oral immunity, and reduce the negative impact of pathogen infection on the human body, which makes it a feasible, effective, and universally applicable anti-infection solution. This review focuses on the immunomodulatory effects of vitamin A, B, C, D, and E and proposes that an omics-based new systemic approach will lead to a breakthrough of the limitations in traditional single-factor single-pathway research and provide the direction for the basic and applied research of vitamin immune regulation and anti-infection in all aspects.

Upregulation of PIK3IP1 monitors the anti-cancer activity of PI3Kα inhibitors in gastric cancer cells.

Gastric cancer remains one of the most malignant cancers in the world. The target-based drugs approved by FDA for gastric cancer treatment include only three targets and benefit a small portion of gastric cancer patients. PIK3CA, a confirmed oncogene, mutates in 7-25% gastric cancer patients. PI3Kα inhibitor BYL719 has been approved for treating specific breast cancer. However, there is no comprehensive study about PI3Kα inhibitor in gastric cancer. In this study, we found pharmacological inhibition or knockdown of PI3Kα effectively inhibited the proliferation of partial gastric cancer cells. Then, we systematically explored the potential biomarkers for predicting or monitoring treatment response according to previous reports and found that basal expression of several receptor tyrosine kinases were related with the sensitivity of gastric cancer cells to BYL719. Next, RNA-seq technique was utilized and showed that BYL719 inhibited Myc targets V2 gene set in sensitive gastric cancer cells, and western blotting further verified that c-Myc was only inhibited in sensitive gastric cancer cells. More importantly, we firstly found BYL719 significantly elevated the expression of PIK3IP1 in sensitive gastric cancer cells, which was also observed in NCI-N87 cell derived xenograft mice models. Meanwhile, knockdown of PIK3IP1 partially rescued the cell growth inhibited by BYL719 in sensitive gastric cancer cells, suggesting the important role of PIK3IP1 in the antitumor activity of BYL719. In conclusion, our study provides biological evidence that PI3Kα is a promising target in specific gastric cancer and the elevation of PIK3IP1 could supply as a biomarker that monitoring treatment response.

Downregulation of USP33 inhibits Slit/Robo signaling pathway and is associated with poor patient survival of glioma.

BACKGROUND: Gliomas are the most common malignant tumors in the central nervous system originating from brain glial cells. Although characterized as highly invasive and highly malignant, few molecular targeting therapies have been developed. Ubiquitin Specific Protease 33 (USP33), a gene encoding a deubiquinating enzyme important in a variety of processes, including Slit-dependent cell migration and beta-2 adrenergic receptor signaling, participates in the development of several malignant tumors, however, its role in the development of glioma has not been evaluated. METHODS: Real-time quantitative PCR was performed to examine the expression of USP33 in glioma tissues and cell lines. Immunohistochemistry was performed to determine USP33 expressions in glioma tissue microarray. Transwell assay was performed to analyze the effect of USP33 on glioma cell line migration. The Kaplan-Meier method and log rank test were applied to evaluate the prognostic value of USP33 expression. Univariate and multivariate Cox proportional hazard regression models were used to identify the independent prognostic factors associated with overall survival (OS) or disease-free survival. RESULTS: The present study demonstrated that USP33 expression was significantly downregulated in glioma tissues. Lower expression of USP33 was associated with a poorer patient disease-free survival and overall survival. In vitro studies revealed that overexpression of USP33 significantly inhibited the migration ability of glioma cells. Mechanistically, USP33 inhibits glioma cell migration by regulating the function of Slit/Robo signaling pathway. CONCLUSIONS: Downregulation of USP33 is associated with poor patient survival of glioma. USP33 inhibits glioma cell migration by Slit/Robo signaling pathway. This mechanism may be applied for development of targeting therapy especially for the high-grade glioma.

Clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome / 中华肝脏病杂志

Objective: To investigate the clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome by prospective, randomized and controlled study. Methods: Patients with chronic hepatitis B with hepatic fibrosis and blood stasis syndrome were selected as the research subjects and randomly divided into a treatment group and a control group. Entecavir plus Biejiajian pills or entecavir plus a simulant of Biejiajian pills were given for 48 weeks. The changes in liver stiffness measurement (LSM) and TCM syndrome scores before and after treatment were compared between the two groups to analyze the correlation. The data between groups were analyzed by t-test/Wilcoxon rank sum test or χ(2) test. Pearson correlation coefficient was used to analyze the correlation between TCM syndrome scores and LSM values. Results: After 48 weeks of treatment, the LSM values of the two groups were significantly lower than those of the baseline (P < 0.001), liver fibrosis was significantly improved, and the LSM values of the treatment group were lower than those of the control group [(8.67 ± 4.60) kPa and (10.13 ± 4.43) kPa, t = -2.011, P = 0.049]. After 48 weeks of treatment, the TCM syndrome scores of the two groups were significantly reduced compared with the baseline (P < 0.001), and the clinical symptoms were significantly relieved, and the total effective rates of the improvement of the TCM syndrome scores in the two groups were 74.19% and 72.97%, respectively, but the differences between the groups were not statistically significant (χ(2) = 0.013, P = 0.910). Correlation analysis showed that there was no obvious trend between TCM syndrome scores and LSM values. There were no serious adverse reactions associated with the drug during the observation period of this study. Conclusion: Based on antiviral treatment with entecavir, regardless of whether it is combined with the Biejiajian pill, it can effectively reduce the LSM value, improve liver fibrosis, reduce TCM syndrome scores, and alleviate symptoms in patients with chronic hepatitis B with liver fibrosis and blood stasis syndrome. Compared with entecavir alone, the combined Biejia pill has greater efficacy in improving liver fibrosis and a favorable safety profile, meriting its implementation and widespread application.