Glioma, the most prevalent primary tumor of the central nervous system (CNS), is also the most lethal primary malignant tumor. Currently, there are limited chemotherapeutics available for glioma treatment, necessitating further research to identify and develop new chemotherapeutic agents. A significant approach to discovering anti-glioma drugs involves isolating antitumor active ingredients from natural products (NPs) and optimizing their structures. Additionally, targeted drug delivery systems (TDDSs) are employed to enhance drug solubility and stability and overcome the blood-brain barrier (BBB). TDDSs can penetrate deep into the brain, increase drug concentration and retention time in the CNS, and improve the targeting efficiency of NPs, thereby reducing adverse effects and enhancing anti-glioma efficacy. This paper reviews the research progress of anti-glioma activities of NPs, including alkaloids, polyphenols, flavonoids, terpenoids, saponins, quinones, and their synthetic derivatives over the past decade. The review also summarizes anti-glioma mechanisms, such as suppression of related protein expression, regulation of reactive oxygen species (ROS) levels, control of apoptosis signaling pathways, reduction of matrix metalloproteinases (MMPs) expression, blocking of vascular endothelial growth factor (VEGF), and reversal of immunosuppression. Furthermore, the functions and advantages of NP-based TDDSs in anti-glioma therapy are examined. The key information presented in this review will be valuable for the research and development of NP-based anti-glioma drugs and related TDDSs.
Humans ; Glioma/metabolism* ; Biological Products/therapeutic use* ; Animals ; Brain Neoplasms/genetics* ; Drug Delivery Systems ; Antineoplastic Agents/therapeutic use* ; Blood-Brain Barrier/metabolism* ; Apoptosis/drug effects*

Objective To investigate the clinical significance of neutrophil to albumin ratio(NAR),neutrophil to lymphocyte ratio(NLR),monocyte to lymphocyte ratio(MLR),platelet to lymphocyte ratio(PLR)and systemic immune-inflammation index(SII)in schizophrenia.Methods A total of 215 patients with schizophrenia admitted to Nanning Social Welfare Hospital from January 2019 to June 2021 were included in schizophrenia group,and 113 healthy people who underwent physical examination in hospital during the same period were included in control group.NAR,NLR,MLR,PLR,SII of two groups were compared,and the correlation between them and the clinical symptom score of schizophrenia and changes after taking antipsychotic drugs were analyzed.Results The levels of NAR,NLR,PLR,MLR and SII in schizophrenia group were significantly higher than those in control group(P<0.05).Spearman correlation analysis showed that NAR,NLR,SII and scale for the assessment of positive symptom scores were negatively correlated(P<0.05).After treatment with antipsychotic drugs,all inflammatory indexes were decreased in schizophrenia group,but NAR and MLR were still significantly higher than those in control group(P<0.05).Conclusion There is an active state of immune inflammation in schizophrenia,and the levels of NAR and MLR do not decrease significantly after treatment with antipsychotic drugs,which may be related to the persistence of schizophrenia symptoms.

Objective To explore the predictive value of CT radiomics and morphological features for the prognosis and survival in non-small cell lung cancer(NSCLC)patients.Methods The clinic data of 300 NSCLC patients(300 lesions)were downloaded from the Cancer Imaging Archive,with 210 randomly selected as the training set and 90 as the test set.According to the prognosis and survival,the patients were divided into two groups with survival period≤3 and＞3 years.3D Slicer software was used to delineate the regions of interest layer by layer in CT images,and the radiomics features were extracted from each region of interest.Both t-test and least absolute shrinkage and selection operator were utilized for radiomics feature screening.Three types of prediction models,namely radiomics model,morphological model and combined model,were constructed with Logistic regression,whose performances were evaluated using the receiver operating characteristic(ROC)curve.Results The differences in radiomics labels and mediastinal lymph node metastasis between the training set and the test set were statistically significant.For radiomics model,morphological model and combined model,the area under the ROC curve was 0.784(95%CI:0.722-0.847),0.734(95%CI:0.664-0.804)and 0.748(95%CI:0.680-0.815)in the training set,and 0.737(95%CI:0.630-0.844),0.665(95%CI:0.554-0.777)and 0.687(95%CI:0.578-0.797)in the test set,which demonstrated that radiomics model had the best diagnostic performance.Conclusion The CT radiomics model can effectively predict the prognosis and survival in NSCLC patients.

Objective To explore the relationship between peripheral blood T lymphocyte subsets and prognosis of patients with advanced non-small cell lung cancer (NSCLC) who received treatment with camrelizumab. Methods We retrospectively collected data from 88 patients with advanced NSCLC who underwent camrelizumab treatment. Peripheral blood lymphocyte subsets were collected from patients before and two months after treatment. Kaplan-Meier curves and Cox regression analysis were employed to investigate the relationship between peripheral blood T lymphocyte subsets and PFS and OS. Results Compared with non-responder group, the baseline peripheral blood CD4+/CD8+ ratio was higher (P=0.038), while the CD8+T lymphocyte percentage was lower (P=0.036) in the responder group. Kaplan-Meier curves showed that a high baseline CD4+/CD8+ ratio was associated with long PFS and OS (P=0.001, P=0.023). Multivariate Cox analysis revealed that the baseline CD4+/CD8+ ratio was a significant predictor for PFS and OS. Additionally, a high post-treatment CD4+/CD8+ ratio and high CD4+T lymphocyte percentage were associated with long PFS (P=0.005, P=0.015), whereas a low post-treatment CD8+T lymphocyte percentage was associated with long PFS and OS (P=0.001, P=0.016). Conclusion The peripheral blood CD4+/CD8+ ratio can serve as a predictive factor for survival of patients with NSCLC treated with camrelizumab.

Objective:To explore the risk stratification and prognostic significance of loss of chromosome Y (LOY) in patients with multiple myeloma (MM).Methods:The clinical data of 193 male patients with newly diagnosed MM admitted to Zhongshan Hospital of Fudan University from January 2018 to January 2020 were analyzed retrospectively and divided into a normal karyotype group(178) and a LOY karyotype group (15) according to the results of their primary conventional cytogenetics. Rank sum test, 2×2 chi-square test and independent sample t-test were used to compare laboratory findings, such as liver and kidney function, immunohistochemistry and cytogenetics, treatment efficacy and survival prognosis, between the two groups. The clinical prognostic significance of LOY was summarized through survival analysis and Cox regression. Results:Among the newly diagnosed male MM patients, 8%(15/178) were confirmed with LOY cases. The proportion of patients with Revised International Staging System(R-ISS) stage Ⅲ was significantly higher in the LOY group (8/15) than that in the normal karyotype group (40/178)(χ 2=7.052, P<0.01). A higher proportion of 1q21 amplification also occurred in the LOY group (10/13 vs 77/162)(χ 2=4.159, P<0.05). The proportion of complete response(CR)/stringent complete response(sCR) in the normal karyotype group after the fourth chemotherapy (63/171) was significantly higher than that in the LOY group (1/15)(χ 2=5.564, P<0.05). The proportion of progressive disease (PD) was lower in the normal karyotype group (16/171 vs 4/15) (χ 2=4.306, P<0.05). The 2-year progression-free survival (PFS) of MM patients for the LOY group was significantly shorter compared to that for the normal karyotype group ( Z=?3.201, P<0.01). Univariate survival analysis showed that PFS was significantly shorter in newly diagnosed MM patients with Creatinine(Cr)≥93 μmol/L, β 2-microglobulin (β 2-MG)≥4.0 mg/L, serum free light chain(sFLC)<0.06, bone marrow plasma cells (BMPC)≥30%, R-ISS stage Ⅲ, failure to achieve CR/sCR after the fourth chemotherapy, with LOY, 1q21 amplification, P53 deletion and t(4;14) ( P<0.05). Cox regression analysis showed that Cr≥93 μmol/L( HR=4.460, 95% CI 1.615-12.314, P=0.004), sFLC<0.06( HR=2.873, 95% CI 1.206-6.849, P=0.017), failure to achieve CR/sCR after the fourth chemotherapy( HR=3.522, 95% CI 1.437-8.634, P=0.006)and with LOY( HR=3.485, 95% CI 1.473-8.249, P=0.006)were independent risk factors for PFS in newly diagnosed MM patients. Conclusions:LOY is an independent risk factor for poor prognosis. It is important for the clinical outcome and prognosis of patients with newly diagnosed MM, and may become a novel clinical assessment indicator.

Background Air pollution is related to the occurrence and development of mental diseases. Olfactory bulb damage might be the potential prodromal symptom and sign of these diseases. The toxicity of diesel exhaust (DE), one of the main sources of air pollution, on olfactory bulb and the underlying mechanisms remain to be elucidated. Objective To explore the toxicity of DE on mouse olfactory bulb and underlying mechanisms. Methods A total of 40 C57BL/6 mice were randomly divided into four groups for exposure to DE by systemic inhalation: control group (filtered air), low exposure group (750 μg·m⁻³ DE), medium exposure group (1500 μg·m⁻³ DE), and high exposure group (3000 μg·m⁻³ DE). The mouse inhalation exposure to DE was performed 1 h per day for 28 d. HE staining was performed to observe pathological changes in mouse olfactory bulb tissue. TUNEL assay was used to observe apop-tosis in olfactory bulb. Kyoto Encyclopedia of Genes and Genomes (KEGG) was exhibited to explore potential mechanisms of olfactory bulb damage associated with DE. Quantitative real-time PCR (qPCR) was used to determine mRNA expression levels of inflammatory factors including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Immunofluorescence staining was conducted to observed the microglia and astrocyte activation in olfactory bulb. Results The HE staining results showed that the number of periglomerular cells in the glomerular layer of olfactory bulb decreased in a dose-dependent manner, and the cells in the granule cell layer of olfactory bulb became disordered after DE exposure. The TUNEL staining showed that TUNEL positive cells in olfactory bulb tissue and neuronal apoptosis increased in the exposed groups compared with the control group (P＜0.05). The KEGG pathway analysis showed that DE associated with significant enrichment of TNF signaling pathway in olfactory bulb tissue. The qPCR results showed that the TNF-α relative expression level significantly increased by 67% and the IL-6 relative expression level by 340% in the DE high exposure dose group compared with the control group (P＜0.05). According to the immunofluorescence staining results, the numbers of activated microglia and astrocytes in olfactory bulb tissue significantly increased in the DE high exposure group, the relative fluorescence intensity of ionized calcium binding adaptor molecule 1 (IBA-1) increased by 120%, the granule cell layer relative fluorescence intensity of glial fibrillary acidic protein (GFAP) increased by 400%, and the glomerular layer relative fluorescence intensity of GFAP increased by 240% than those in the control group (P＜0.05). Conclusion Inhalation exposure to DE can lead to glial cell activation including microglia and astrocytes in olfactory bulb tissue by activating inflammatory pathways and releasing inflammatory factors TNF-α and IL-6, leading to neuronal apoptosis in olfactory bulb tissue.

OBJECTIVE: To analyze the characteristics of genetic variants among children with refractory epilepsy (RE). METHODS: One hundred and seventeen children with RE who had presented at the Affiliated Jinhua Hospital of Zhejiang University School of Medicine from January 1, 2018 to November 21, 2019 were selected as the study subjects. The children were divided into four groups according to their ages of onset: < 1 year old, 1 ~ 3 years old, 3 ~ 12 years old, and >= 12 years old. Clinical data and results of trio-whole exome sequencing were retrospectively analyzed. RESULTS: In total 67 males and 50 females were included. The age of onset had ranged from 4 days to 14 years old. Among the 117 patients, 33 (28.21%) had carried pathogenic or likely pathogenic variants. The detection rates for the < 1 year old, 1 ~ 3 years old and >= 3 years old groups were 53.85% (21/39), 12.00% (3/25) and 16.98% (9/53), respectively, with a significant difference among the groups (χ² = 19.202, P < 0.001). The detection rates for patients with and without comorbidities were 33.33% (12/36) and 25.93% (21/81), respectively (χ² = 0.359, P = 0.549). Among the 33 patients carrying genetic variants, 27 were single nucleotide polymorphisms (SNPs) or insertion/deletions (InDels), and 6 were copy number variations (CNVs). The most common mutant genes were PRRT2 (15.15%, 5/33) and SCN1A (12.12%, 4/33). Among children carrying genetic variants, 72.73% (8/11) had attained clinical remission after adjusting the medication according to the references. CONCLUSION 28.21% of RE patients have harbored pathogenic or likely pathogenic variants or CNVs. The detection rate is higher in those with younger age of onset. PRRT2 and SCN1A genes are more commonly involved. Adjusting medication based on the types of affected genes may facilitate improvement of the remission rate.
Infant ; Female ; Male ; Humans ; Child ; Infant, Newborn ; Child, Preschool ; DNA Copy Number Variations ; Drug Resistant Epilepsy/genetics* ; Retrospective Studies ; Polymorphism, Single Nucleotide

Objective:To construct a health education program for enterostomy patients based on the guideline of Facilitating Client Centered Learning. Methods:From July to October 2022, based on the adaptability survey and literature research of the previous guidelines, the first draft of the health education program for enterostomy patients was formed. A total of 13 experts were selected using purposive sampling method, and two rounds of expert consultation were conducted through the Delphi method on the first draft of the program to build the final health education program for enterostomy patients. We calculated the authority, enthusiasm, coordination, and concentration of experts.Results:The health education program for enterostomy patients included 3 first-level indicators, 9 second-level indicators, and 31 third-level indicators. The effective response rates of the first and second rounds of consultation questionnaires were both 100.0%, and the authority coefficients of experts were both greater than 0.7. In the second round of consultation, the Kendal coordination coefficients of the importance of the first, second and third level indicators were 0.231, 0.154 and 0.182 ( P<0.05), and the Kendal coordination coefficients of the feasibility of the first, second and third level indicators were 0.216, 0.154 and 0.129 ( P<0.05), with coefficients of variation < 0.25. Conclusions:The health education program for enterostomy patients based on the guideline of Facilitating Client Centered Learning is practical and scientific, and can provide guidance for clinical practice.

Objective:To investigate the effects of antibiotic treatment and antibiotics combined with surgery treatment on the prognosis of patients with infective endocarditis (IE).Methods:The clinical data and prognosis of all patients diagnosed as IE discharged from Shanghai Jiao Tong University Affiliated Sixth People′s Hospital from June 2011 to May 2021 were collected. There were 240 IE patients, divided into antibiotic treatment group and the antibiotics combined with surgery group according to the treatment methods. The clinical characteristics and prognosis of the IE patients were compared between the two groups, so as to investigate the timing of surgery for IE patients and to analyze the effects of the two treatment methods on the prognosis of IE patients.Statistical analysis methods including Wilcoxon rank sum test, chi-square test, Kaplan-Meier survival analysis and Cox regression analysis were used when appropriate.Results:Of the 240 patients with IE, 63 cases were only treated with antibiotics and 177 cases were treated with antibiotics combined with surgery. After propensity score matching (PSM), one-year mortality rate of the IE patients in the antibiotics combined with surgery group was 11.1%(4/36), which was significantly lower than that in the antibiotic treatment group (33.3%(12/36), χ2=5.14, P=0.023). The median values of left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD) and left ventricular fractional shortening (LVFS) in the antibiotics combined with surgery group were 59%, 47 mm and 31%, respectively, which were significantly lower than those before surgery (63%, 54 mm and 34%, respectively, Z=6.19, 9.36 and 6.11, respectively, all P<0.001). The most common surgical indication was moderate to severe heart failure, and there was no significant difference between the early operation group and the late operation group (both P>0.050). The one-year cumulative survival rate of antibiotics combined with surgery group was 94.9%, which was significantly higher than that in the antibiotic treatment group (83.2%, χ2=7.38, P=0.007). Heart failure and Pitt bacteremia scores≥4 were the independent risk factors for one-year all-cause death of the IE patients (hazard ratio ( HR)=5.668 and 19.392, respectively, both P<0.050). Hospital days and antibiotics combined with surgery were independent related factors for reducing the risks of one-year all-cause death ( HR=0.931 and 0.299, respectively, both P<0.050). Pitt bacteremia scores≥4 had the greatest impact on one-year prognosis of the IE patients. Conclusions:Surgery could significantly improve cardiac function and one-year prognosis of the IE patients. IE patients with heart failure and Pitt bacteremia score≥4 should be actively treated.

We present a case of a postmenopausal women with hyperandrogenic symptoms and virilization signs , such as hirsutism, alopecia, acne and clitoromegaly, which was pathologically confirmed to be an ovarian steroid cell tumor, not otherwise specified(NOS). The levels of testosterone, dehydroepiandrosterone sulfate and estradiol in serum were increased, while the levels of luteinizing hormone and follicle stimulating hormone were decreased. Computed tomography(CT) scan and magnetic resonance imaging(MRI) identified a solid, left ovarian tumor and detected an additional tumor of hypodensity in the left adrenal gland. ACTH stimulation test, hCG stimulation test, adrenal and ovarian vein sampling indicated that excessive androgens were derived from the ovary. After the injection of gonadotropin hormone analogues(GnRHa), testosterone levels dropped to the normal range. Laparoscopic bilateral adnexectomy was performed, and pathology indicated NOS. The purpose of this report is to improve the understanding of NOS with hyperandrogenic presentation.