Objective To construct an assay for early infection diagnosis of Angiostrongylus cantonensis based on gold nanorod polymerization.Methods Stable gold nanorods were synthesized by the gold seed growth method,and labeled with different concentrations of sulfhydrylated crude and purified antigens of lar-vae and adults of Angiostrongylus cantonensis,and their excretory and secretory antigens,and then scanned the longitudinal surface plasmon resonance(LSPR)of the stable gold nanorods by ultraviolet-visible(UV-Vis)spectrophotometry,and screened for the optimal labeled antigens for the detection of different infection time after infection of rats with Angiostrongylus cantonensis.The displacement changes were screened to se-lect the best labeled antigens for the detection of serum antibodies and positive sera of series of dilution gradi-ents at different infection times(5,7,14,21 d)after infection with Angiostrongylus cantonensis in rats,and at the same time,the enzyme-linked immunosorbent assay(ELISA)was set up for the same test.Kappa test was used to compare the consistency of the two assays.Results Gold nanorods with stable aspect ratio were suc-cessfully prepared.The gold nanorods labeled with 10 μg/mL of adult purified antigen had a maximum LSPR shift of 40 nm,and were able to detect serum antibodies in rats 5 d after mild,moderate and severe infection with Angiostrongylus cantonensis,as well as positive sera at a maximum dilution of 1∶600.The ELISA was able to detect serum antibodies in rats after 14 d of mild infection,and 7 d of moderate and severe infection,as well as positive sera at a maximum dilution of 1∶200.The ELISA detected positive serum antibodies in rats after 14 d of mild infection and 7 d of moderate and severe infection,as well as in rats at a maximum dilution of 1∶200.The Kappa value of the two methods was 0.750(P<0.01),and the results of the two methods had strong consistency.Conclusion A polymerized gold nanorod assay for early and rapid diagnosis of An-giostrongylus cantonensis infection is successfully constructed.

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Naringenin (4,5,7-trihydroxyflavonoid) is a naturally occurring bioflavonoid found in citrus fruits, which plays an important role in metabolic syndrome, neurological disorders, and cardiovascular diseases. However, the pharmacological mechanism and biological function of naringenin on anti-angiogenesis and anti-tumor immunity have not yet been elucidated. Our study firstly demonstrates that naringenin inhibits the growth of hepatocellular carcinoma (HCC) cells both in vivo and in vitro. Naringenin diminishes the ability of HCC cells to induce tube formation and migration of human umbilical vein endothelial cells (HUVECs) and suppresses neovascularization in chicken chorioallantoic membrane (CAM) assays. Meanwhile, in vivo results demonstrate that naringenin can significantly upregulate level of CD8⁺ T cells, subsequently increasing the level of immune-related cytokines in the tumor immune microenvironment. Mechanistically, we found that naringenin facilitate the K48-linked ubiquitination and subsequent protein degradation of vascular endothelial growth factor A (VEGFA) and mesenchymal-epithelial transition factor (c-Met), which reduces the expression of programmed death ligand 1 (PD-L1). Importantly, combination therapy naringenin with PD-L1 antibody or bevacizumab provided better therapeutic effects in liver cancer. Our study reveals that naringenin can effectively inhibit angiogenesis and anti-tumor immunity in liver cancer by degradation of VEGFA and c-Met in a K48-linked ubiquitination manner. This work enlightens the potential effect of naringenin as a promising therapeutic strategy against anti-angiogenesis and anti-tumor immunity in HCC.

Bone grafting is a primary method for treating bone defects. Among various graft materials, xenogeneic bone substitutes are widely used in clinical practice due to their abundant sources, convenient processing and storage, and avoidance of secondary surgeries. With the advancement of domestic production and the limitations of imported products, an increasing number of bone filling or grafting substitute materials isentering clinical trials. Relevant experts have drafted this consensus to enhance the management of medical device clinical trials, protect the rights of participants, and ensure the scientific and effective execution of trials. It summarizes clinical experience in aspects, such as design principles, participant inclusion/exclusion criteria, observation periods, efficacy evaluation metrics, safety assessment indicators, and quality control, to provide guidance for professionals in the field.
Humans ; Bone Substitutes/therapeutic use* ; Randomized Controlled Trials as Topic/methods* ; Consensus ; Bone Transplantation ; Research Design

Objective:To discuss the expression and clinical significance of inositol polyphosphate-4-phosphatase type Ⅱ(INPP4B)gene in hepatocellular carcinoma(HCC)based on The Cancer Genome Atlas(TCGA)database and experimental verification with clinical samples.Methods:Based on data from 424 clinical samples in the TCGA database(including 374 HCC tissues and 50 paracarcinoma tissues),Kaplan-Meier method and Cox regression analysis were used to evaluate the relationship between INPP4B gene and the clinical characteristics and survival prognosis of the HCC patients.The correlations between INPP4B gene and the number of 24 types of immune cells,matrix,immune cell infiltration and tumor purity in tumor tissue,and the expression level of the high-frequency mutant gene tumor protein 53(TP53)in HCC were analyzed.The clinicopathological data and paraffin-embedded tissue sections of 60 HCC patients treated with surgical resection from December 2022 to December 2023 were collected.According to clinical diagnosis,they were divided into poorly differentiated group(HCC-L group),moderately differentiated group(HCC-M group)and well-differentiated group(HCC-H group),with 20 cases in each group;20 patients during the same period who underwent biopsy and were pathologically diagnosed as non-tumor were selected as normal group,and their clinicopathologic data and liver tissue paraffin sections were collected.HE staining was used to observe the pathomorphology of HCC tissue and normal liver tissue of the subjects in various groups;immunohistochemistry method was used to detect the expressions of Ki-67 and INPP4B proteins in the HCC tissue and normal liver tissue of the subjects in various groups.Results:The TCGA database analysis results showed that compared with normal tissue,the expression level of INPP4B mRNA in HCC tissue was significantly increased(P<0.01).Compared with INPP4B low expression group,the overall survival(OS)of the patients in INPP4B high expression group was significantly prolonged(P<0.05).The univariate Cox regression analysis results showed that tumor stage,pathological stage,tumor status and residual tumor had impacts on OS of the HCC patients(P<0.05).The univariate regression analysis results showed that the INPP4B prognostic risk model score ratio was HR=0.781,95％confidence interval(CI):0.552-1.105,P=0.168.The AUC value for the impact of INPP4B on OS of the HCC patients was 0.558,indicating that the INPP4B gene prognostic risk model had certain predictive value in survival prognosis.The INPP4B mRNA expression level was not correlated with TNM stage,stage,patient gender,age,race or body mass index(BMI)(P>0.05).In tumor tissue with high and low INPP4B expression,22 types of immune cells showed statistically significant differences(P<0.05);the INPP4B mRNA expression level was positively correlated with the number of 23 types of immune cells except T helper(Th)17 cells(r>0),among which all Th cells except natural killer(NK)CD56+cells were statistically significant(P<0.01);INPP4B was significantly correlated with matrix(r=0.475),immune cell infiltration(r=0.641)and tumor purity(r=0.599)in tumor tissue(P<0.01).INPP4B was correlated with TP53(r=0.287,P<0.01).The HE staining results showed that clear and complete lobular structure,neatly arranged cells and slight inflammatory cell infiltration were observed in liver tissue of the subjects in normal group;completely destroyed lobular structure,significant hepatocellular steatosis,massive inflammatory cell infiltration,and lesions such as ballooning degeneration and small cell hyperplasia in some cells were observed in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups,and the lower the HCC differentiation degree,the more severe the tissue destruction;The immunohistochemistry results showed that compared with normal group,the expression levels of Ki-67 protein in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups were significantly increased(P<0.01),and the lower the differentiation degree of the HCC patients,the higher the Ki-67 positive rate.Brownish-yellow granules evenly distributed in the cells and INPP4B protein was highly expressed in liver tissue of the subjects in normal group;compared with normal group,the expression levels of INPP4B protein in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups were significantly decreased(P<0.01),and the lower the differentiation degree of the HCC tissue,the lower the INPP4B positive rate.Conclusion:INPP4B is a protective factor for the prognosis of HCC patients;as a new tumor suppressor gene,INPP4B may become a potential target for new drug screening in HCC treatment.

Objective:To analyze the influencing factors and improvement paths of the cultivation of full-time doctoral scientific and technological innovation ability in large public hospitals, and propose countermeasures and suggestions.Methods:This studyed conducted a survey and analysis of 122 doctors from Linyi People′s Hospital in Shandong Province, and completed a current situation study based on the analysis results.Results:There was no significant difference between the two groups in gender, age, degree type, professional category, discipline level, Graduate School type, job type and other indicators. There were significant differences between the two groups in scientific research topic selection ability score, project design ability score, data analysis ability score, data interpretation ability score, project approval in recent 5 years, project level, number of SCI journal papers published in recent 5 years, cumulative impact factors of SCI journal papers, and annual number of academic activities ( P<0.05). Conclusions:The hospital can improve the scientific and technological innovation ability of full-time doctors by setting up a special cultivation plan, establishing an interdisciplinary team, optimizing scientific research management services, improving the evaluation and assessment system, and improving welfare protection.

Objective:To investigate the impact of exogenous hypoxia-inducible factor 1α(HIF-1α)on glucose metabolism-related proteins and neurological function in the hippocampal CA1 region of rats with cerebral ischemia.Methods:Adult male SD rats were randomly assigned to four groups: sham operation group(Sham group), cerebral ischemia reperfusion group(CIR group), recombinant adenovirus empty vector intervention group(Ad group), and recombinant adenovirus HIF-1α gene intervention group(AdHIF-1α group), each consisting of 12 rats.A rat model of cerebral ischemia-reperfusion injury was induced using the modified suture method, and neurological deficits were assessed using the Longa method.In line with previous protocols, exogenous Ad and AdHIF-1α were introduced into the lateral ventricle of rats in the Ad and AdHIF-1α groups, respectively.After 28 days of observation, the animals were euthanized.Hippocampal tissue was collected for analysis, including Hematoxylin-eosin(HE)staining, terminal transferase labeling in situ(TUNEL)staining, and Nissl staining to evaluate pathological changes and neuronal survival in the hippocampal CA1 region.Western blot was performed to assess the expression levels of HIF-1α, glucose transporter 1(GLUT1), glucose transporter 3(GLUT3), and 6-phosphofructose-2-kinase/fructose-2, 6-bisphosphatase 3(PFKFB3)proteins in the hippocampal tissue.Results:Following 28 days of recombinant adenovirus HIF-1α gene therapy, rats in the AdHIF-1α group exhibited reduced neurological deficits compared to the CIR group( P<0.05).Histopathological analysis of nerve cells in the CA1 region of the hippocampus showed significant improvement, with an increase in the number of surviving nerve cells and a decrease in apoptotic cells( P<0.01).Western blot results indicated an upregulation of HIF-1α expression in the hippocampus of the CIR group compared to the Sham group, along with increased levels of glucose metabolism-related proteins(GLUT1, GLUT3, and PFKFB3)(all P<0.05).Furthermore, elevating HIF-1α expression through AdHIF-1α led to a further increase in the expression of glucose transporters(GLUT1, GLUT3, and PFKFB3)in the AdHIF-1α group, demonstrating statistically significant differences compared to the CIR group(all P<0.05).Notably, there were no statistically significant variances in the aforementioned parameters between the Ad group and the CIR group(all P>0.05). Conclusions:The AdHIF-1α gene has the potential to enhance neurological function, promote nerve cell survival, and decrease nerve cell apoptosis.This effect is likely achieved by increasing HIF-1α expression in the hippocampus, subsequently up-regulating GLUT1, GLUT3 and PFKFB3 expression, and ultimately improving glucose metabolism supply.Overall, this gene shows promise in protecting the brain.

OBJECTIVE To establish an HPLC method for investigating the stability of mandelonitrile in commonly used solvents and quantitation determination of mandelonitrile in Jian’er Qingjie mixture. METHODS The assay was performed on an Agilent TC-C18(250 mm×4.6 mm, 5 μm) column with a mobile phase consisting of acetonitrile-0.1% phosphoric acid(23∶27) pumped at a flow rate of 1.0 mL·min–1. The column temperature was 30 ℃ and the detection wavelength was set at 207 nm. The stability of the mandelonitrile solution prepared with solvents such as methanol, 95% ethanol, acetonitrile, water, phosphoric acid solution with pH 2.0−6.0, and acetonitrile solution containing 1.0% glacial acetic acid was investigated using the peak reduction rate as the indicator. RESULTS Mandelonitrile was labile in methanol, 95% ethanol or water and relatively stable in acetonitrile. The standard solutions of mandelonitrile prepared with phosphoric acid solutions at pH 2.0−3.5 or acetonitrile containing 1.0% glacial acetic acid were stable in 12 h. The linear range of mandelonitrile was 1.033−294.987 µg·mL–1(r=0.999 9) and the average recovery was 97.4% with RSD of 0.6%(n=9). The content range of mandelonitrile in 16 batches of Jian’er Qingjie mixture produced by 5 manufactures was 3.854−154.578 µg·mL–1. CONCLUSION The established method is simple and accurate. It can be used for the quality control of Jian’er Qingjie mixture. For almond aromatic water and its preparations, the influence of solvent on stability of mandelonitrile should be noticed.

Objective:To explore the social and physical anhedonia and its relationship to intrinsic motivation in patients with schizophrenia.Methods:One hundred and twenty-five stable schizophrenic patients from three psychiatric hospitals in Hefei, Wuhu and Beihai, and 101 healthy controls from same communities were recruited.All subjects completed Chinese version of revised social anhedonia scale(RSAS-C), Chinese version of revised physical anhedonia scale(RPAS-C) and intrinsic motivation inventory for schizophrenia research(IMI-SR), while positive and negative syndrome scale(PANSS) and Calgary depression scale for schizophrenia(CDSS) were used to assess the clinical symptoms of schizophrenic patients.All analyses were conducted by SPSS 26.0 software.The Mann-Whitney U test and covariance analysis were used for comparison between the groups, and Spearman correlation and multiple logistic regression analysis were used to explore the association between the anhedonia and intrinsic motivation in schizophrenics. Results:Compared with controls, the RSAS-C (10.00(6.00, 14.00) vs 11.00(8.00, 15.00), Z=-2.187, P<0.05) and RPAS-C (12.00(7.50, 20.00) vs 16.00(10.00, 23.00), Z=-3.026, P<0.01) scores in patients were higher, but the differerce between the groups disappeared after controlling age, sex and years of education.The IMI-SR perceived choice subscore (31.00(28.00, 39.00 vs 36.00(31.00, 42.00), Z=-3.172, P<0.01) were lower, while value/usefulness subscores (41.00(35.00, 45.00) vs 36.00(32.00, 42.00), Z=-3.387, P<0.01) were higher in patients than those in controls, and there was no significant difference between the total score and interest/enjoyment subscore(both P<0.05). In patents, Spearman correlation analysis showed that the RSAS-C and RPAS-C scores were significant negatively correlated with the IMI-SR total scores and interest/enjoyment subscore, perceived choice and value/usefulness( r=-0.193--0.364, all P<0.05), which still existed after controlling age, sex, years of education, course of disease, antipsychotic dose, and scores of PANSS and CDSS.Logistic regression analysis showed that the score of RSAS-C( B=-0.096, 95% CI=0.836-0.998, P=0.025) and perceived choice subscore( B=-0.110, 95% CI=0.823-0.974, P=0.010) had negative effects on the IMI-SR total score. Conclusion:There is a correlation between anhedonia and intrinsic motivation in patients with schizophrenia, the higher the social anhedonia, the lower the intrinsic motivation to participate in cognitive activities, suggesting that intervention for social anhedonia may have significance in improving the intrinsic motivation of patients with cognitive rehabilitation therapy.

Objective:To identify the pathogenic characteristics of a suspected gonadal mosaicism Becker muscular dystrophy (BMD) family, and provide provide basis for pregnancy selection of similar families.Methods:A BMD family admitted to Hunan Jiahui Genetics Hospital from June 2012 to September 2019 was systematically reviewed. The medical history and family history of the proband were checked, and multiplex ligation-dependent probe amplification was used to detect the deletion/duplication of 79 exons of the Duchenne muscular dystrophy (DMD) gene in the proband, fetuses, and parents. Moreover, potential variants were verified by combining PCR amplification, short tandom repeat polymorphic linkage analysis, and real-time fluorescence quantitative PCR. High-quality embryos are screened for transplantation after preimplantation genetic testing for monogenic (PGT-M). And amniotic fluid was collected in the second trimester for prenatal diagnostic verification.Results:According to the phenotype analysis of the proband, the initial clinical diagnosis was BMD, and the exon 45-50 deletion in DMD gene was detected. The mutation was not detected in the mother′s peripheral blood, but when she was pregnant again, the prenatal diagnosis showed that the fetus had the same deletion mutation as the proband. Neither of two vitro embryos tested by PGT-M has the deletion mutation, then single embryo transfer was performed nor was pregnancy successful. After confirmation of prenatal diagnosis during pregnancy, a normal baby girl was born by full-term cesarean section.Conclusions:This BMD family was a family with two consecutive BMD homodeletion mutations, and the mutation of the DMD gene was not detected in the peripheral blood of the proband′s mother and two embryonic cells, suggesting that the mother may be a gonad chimeric carrier of this deletion mutation. The combined application of prenatal diagnosis and PGT-M provides a reference approach to effectively avoid the birth of similar children.