Advances in Salmonella-mediated targeted tumor therapy / 药学学报

italic>Salmonella has emerged as a promising tumor-targeting strategy in recent years due to its good tumor targeting ability and certain safety. In order to further optimize its therapeutic effect, scientists have tried to modify Salmonella, including its attenuation and drug loading. This paper summarizes the mechanism and research progress of Salmonella-mediated targeted tumor therapy, and introduces the strategies and related progress of its modification and optimization. At the same time, the advantages, current challenges and future development directions of Salmonella-mediated tumor therapy are summarized.

Comparing the predictive value of parameters extracted from circular ROIs with whole liver histogram on Gd-EOB-DTPA enhanced MRI for postoperative liver failure in focal liver lesions / 中华肝胆外科杂志

Objective:To compare the predictive value of parameters extracted from circular region-of-interest (ROI) with whole-liver histogram on gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced T 1 map for postoperative liver failure in patients with liver focal lesions. Methods:The data of patients who underwent Gd-EOB-DTPA-enhanced MRI for focal liver lesions in Zhongshan Hospital, Fudan University from March 2016 to March 2018 were analyzed retrospectively. Forty patients were enrolled, including 30 males and 10 females, aged (56.6±12.1) years. According to the occurrence of postoperative liver failure, forty patients were divided into liver failure group ( n=14) and control group ( n=26). The parameters extracted from circular ROIs and whole liver histogram on T 1 map before Gd-EOB-DTPA enhancement and in hepatobiliary phase (HBP) were compared between the two groups. The receiver operating characteristic (ROC) curve was used to evaluate the value of these parameters in predicting postoperative liver failure. Results:The mean, standard deviation, median and 95% quantile of T 1 HBP in histogram parameters of liver failure group were significantly higher than those of control group (all P<0.05). The three parameters extracted from circular ROIs were not effective in predicting liver failure after hepatectomy (all P>0.05). Among all the liver histogram parameters, the area under the ROC curve of the 95% quantile before T 1 enhancement for predicting postoperative liver failure was 0.702 (95% CI: 0.523-0.881), the standard deviation of T 1 HBP was 0.739 (95% CI: 0.568-0.910), and the 95% quantile of T 1 HBP was 0.721 (95% CI: 0.540-0.903). The predictive efficacy were good (all P<0.05). Among them, the predictive performance of T 1 HBP standard deviation was the best, the area under the ROC curve was 0.739, the sensitivity was 85.7%, the specificity was 57.7%, and the best threshold was 54.8 ms. Conclusions:When Gd-EOB-DTPA enhanced T 1 mapping is used to predict postoperative liver failure in patients with focal liver lesions, the whole-liver histogram analysis is superior to the conventional circular ROI-based statistical method.

Identification and expression analysis of flavonoid O-methyltransferases gene family in Artemisia argyi / 药学学报

italic>Artemisia argyi (A. argyi) is a Chinese herbal medicine in China. The main active components are volatile oils, flavonoids, and other compounds, which have various pharmacological activities. Methoxylated flavonoids are the main active ingredients in A. argyi. Flavonoid O-methyltransferase (FOMT) is a key enzyme in the O-methylation of flavonoids. In order to further understand the function and characteristics of FOMT proteins, this paper carried out the whole genome mining and identification of FOMT genes in A. argyi and performed phylogenetic, chromosomal localization, gene sequence characterization, subcellular localization prediction, protein structure, gene structure analysis, and expression pattern analysis. The results showed that a total of 83 FOMT genes were identified in the genome of A. argyi. The phylogenetic tree shows that FOMT genes are divided into two subgroups, CCoAOMT (caffeoyl CoA O-methyltransferase) subfamily (32 genes) and COMT (caffeic acid O-methyltransferase) subfamily (51 genes). Gene sequence analysis showed that the number of amino acids encoded by FOMT was 70-734 aa, the molecular weight was 25 296.55-34 241.3 Da, and the isoelectric point was 4.51-9.99. Compared with 32 members of the CCoAOMT subfamily, nearly 1/3 of the 51 members of the COMT subfamily were hydrophobic proteins and 2/3 were hydrophilic proteins. Subcellular localization prediction showed that more than 80% of CCoAOMT subfamily members were located in the cytoplasm, and 96% of COMT subfamily members were located in the chloroplast. COMT subfamily members have more motifs than CCoAOMT subfamily members. The N-terminal motifs of COMT subfamily proteins are relatively variable, while the C-terminal motifs are relatively conserved. Expression pattern analysis showed that CCoAOMT subfamily members were mainly expressed in roots, while COMT members were mainly expressed in leaves. Some FOMTs showed the tissue expression specificity by real-time quantitative PCR analysis, especially in leaves. In this study, we identified and analyzed the FOMT gene family in A. argyi, and provided a theoretical basis for further research on the function of FOMTs and the biosynthesis of methylated flavonoids in A. argyi.

Sleep-improving mechanisms of Jiu Wei Bu Xue Oral Liquid on regulating Glu/GABA balance in insomnia rats based on network pharmacology and experimental verification / 药学学报

This study aimed to investigate the mechanism of Jiu Wei Bu Xue Oral Liquid on insomnia rats combining the methods of network pharmacology, molecular docking and experimental verification. UPLC-Q-TOF-MS/MS method and TCMIP, TCMSP databases were used to collect the ingredients and targets of Jiu Wei Bu Xue Oral Liquid. Protein-protein interactions and network analysis were performed to screen the key network targets and putative active ingredients of Jiu Wei Bu Xue Oral Liquid in treatment of insomnia, and then following by biological function and KEGG pathway analysis. Then binding ability for key network targets and putative active ingredients were predicted with molecular docking. The prediction targets were validated in para-chlorophenylalanine (PCPA) induced insomnia rats with administration of Jiu Wei Bu Xue Oral Liquid (2, 4, 8 mL·kg-1) for 7 days. Pentobarbital sodium induced sleeping test were performed to evaluate the synergistic sleep-aiding effect of Jiu Wei Bu Xue Oral Liquid. Then glutamic acid (Glu), γ-aminobutyrate (GABA) content and glutamate decarboxylase 1 (GAD67) activity in hypothalamus or hippocampus were evaluated, and the expressions of GAD67, γ-aminobutyric acid receptor subunit α1 (GABRA1) and γ-aminobutyric acid receptor subunit β2 (GABRB2) in hippocampus were detected by qRT-PCR and Western blot methods. Animal experiments were approved by the Institutional Committee on Animal Care of Guangxi Institute of Chinese Medicine & Pharmaceutical Science (the number of permission: 2022060802). Results showed that 16 key network targets and 16 putative active ingredients were obtained by analyzing the herbs-ingredients-targets network of Jiu Wei Bu Xue Oral Liquid in treatment of insomnia. Network pharmacology and molecular docking all indicated these active ingredients, for example atractylenolide Ⅲ, showed better binding ability with GABRA1 and GABRB2. Animal study indicated that, compared to PCPA-induced insomnia model, Jiu Wei Bu Xue Oral Liquid remarkably shortened the sleeping latency and increased the sleeping duration, increased GAD67 activity and the production of GABA in hippocampus of insomnia rats, as well as the expressions of GAD67, GABRA1 and GABRB2, while decreased Glu content in hypothalamus, leading to decreasing of Glu/GABA ratio and recovery of Glu-GABA balance. These results indicated that Jiu Wei Bu Xue Oral Liquid improved insomnia symptoms and helped maintain the Glu-GABA balance within hypothalamus and hippocampus, and reduced the excitatory neurotoxicity within brain. The mechanism may due to the elevation of GAD67 expression and enzyme activity, and the enhancement of type-A GABA receptor (GABAAR)-mediated neurons inhibition.

Advances of mitophagy involved in diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

Mitochondrial function is essential for the viability of aerobic eukaryotic cells, as mitochondria provide energy through the generation of adenosine triphosphate(ATP), regulate cellular metabolism, provide redox balancing, participate in immune signaling, and initiate apoptosis. Mitophagy refers to the selective elimination of dysfunctional mitochondria in cells, thereby achieving mitochondrial quality control and maintaining cell homeostasis. Recent studies have indicated that abnormal mitophagy is involved in the development of various eye diseases, such as diabetic retinopathy(DR), age-related macular degeneration and glaucoma. In this review, we summarize the current knowledge on the definition of mitophagy, and present the results of various studies using cell culture, animal, and human tissue models. Additionally, we review the molecular process of mitophagy and its role in DR, thus providing novel ideas for the treatment of DR.

Research advances in the size selection of implantable collamer lens / 国际眼科杂志(Guoji Yanke Zazhi)

The implantable collamer lens(ICL)is a widely popular option for the correction of refractive errors. ICL implantation brings a whole new dimension to the vision, from the anterior chamber phakic ICL to the posterior and central hole ICL. Even though there are fewer reported complications, ICL size selection remains challenging due to the differences in device measurements and ICL sizing formulas. With the widening comprehensiveness of ICL implantation and the ongoing development of ophthalmic devices and technologies, particularly the advent of artificial intelligence, more and more indicators such as sulcus-to-sulcus(STS), crystalline lens rise(CLR), angle-to-angle(ATA), the iris pigment end to the iris pigment end(PTP), anterior chamber width(ACW), and anterior chamber angle(ACA)are providing references in the selection of ICL size, this article provides a review of ICL size selection.

Natural Plant-derived Polysaccharides Against Cervical Cancer： A Review / 中国实验方剂学杂志

Cervical cancer is a gynecological malignant tumor with a high incidence in the world. With the insidious onset and lack of obvious symptoms and signs in the early stage， 13% of cervical cancer patients are diagnosed in the advanced stage of the disease， and the 5-year survival rate of metastatic cervical cancer is only 16.5%. So far， surgery and radiotherapy/chemotherapy are still the basic means for the treatment of cervical cancer. However， with the emergence of toxicity， drug resistance， and other side effects， there are still some limitations in the clinical application of these therapies. In recent years， natural compounds represented by polysaccharides have been found to have a significant anti-cervical cancer effect， which has attracted extensive attention from researchers in China and abroad. Widely distributed in the roots， stems， leaves， flowers， and fruits of higher plants， plant-based polysaccharides are important components of natural polysaccharides， as well as multimers with a complex structure and biological response regulators， which have been widely studied in the fields of cancer， cardiovascular， endocrine， and other diseases. This study reviewed the research on the anti-cervical cancer effect and mechanism of natural plant-derived polysaccharides by consulting the literature in the past 20 years to bring breakthroughs in the research and development of anti-cervical cancer new drugs. Through the literature review， the results indicated that natural plant-derived polysaccharides could exert anti-tumor effects by inhibiting cell proliferation， promoting apoptosis， inhibiting invasion and migration， promoting autophagy， arresting cell cycle of cervical cancer cells， regulating epithelial-mesenchymal transition （EMT）， resisting oxidative stress， inhibiting tumor angiogenesis， improving immunomodulatory activity， and regulating signaling pathways. It should be noted that in the current research on natural plant-derived polysaccharides against cervical cancer， the bioavailability of some natural polysaccharides is low and a considerable proportion of the research is limited to the in vitro experiment. Therefore， it is urgent to carry out more clinical experimental studies on the anti-cervical cancer of natural plant-based polysaccharides to obtain a more reliable theoretical and practical basis.

Relationship Between Metabolic Remodeling of Endothelial Cells and Tumor Angiogenesis Based on "Yin Fire" Theory and Intervention of Chinese Medicine / 中国实验方剂学杂志

Endothelial cells in the inner wall of blood vessels respond to physical and chemical signals of the body by regulating vascular homeostasis， vascular tension， cell adhesion， cell proliferation， coagulation resistance and inflammatory factors， to maintain the stability of blood vessels. Angiogenesis is the key condition for tumor evolution， and the pathological mode of tumor angiogenesis provides nutrients and oxygen for tumor growth and promotes its proliferation. In recent years， endothelial cells have participated in tumor vascular infiltration and driven angiogenesis， which is considered to be the point link in tumor metastasis. By regulating metabolic remodeling， vascular endothelial cells provide the materials and energy needed in the process of tumor angiogenesis， and their abnormal metabolic characteristics facilitate their adaption to the changes of tumor microenvironment， which is often regarded as an important basis for tumor angiogenesis. The ''Yin fire'' theory in traditional Chinese medicine， originating from Huangdi's Internal Classic （Huang Di Nei Jing）， originally meant Yin deficiency generates internal heat， and belonged to the category of fire of internal injury. After the deduction and changes by physicians over the ages， the pathogenesis of ''spleen and stomach Qi deficiency-Yin fire rising-Qi and fire disharmony'' was gradually formed. The pathogenesis of metabolic remodeling of endothelial cells manifests the pathological characterization of Yin fire in an objective way， which is consistent with the disease state of uncontrolled and hyperactive tumor neovascularization. Changes in spleen and stomach Qi deficiency as well as imbalance of Qi movement lead to the failure of water and food in distribution， and thus metabolic disorders occur. Long term retention turns in phlegm and blood stasis， which combat with blood vessels， and result in abnormal local environment （formation of tumor microenvironment）， adverse pulse channel （imbalance of endothelial cell metabolism）， and tumor neovascularization. Under the guidance of ''Yin fire'' syndrome elements and by focusing on the correlation between Qi and fire， prescriptions are made based on the treatment method of ''strengthening the body and regulating Qi'' to regulate the metabolic function of endothelial cells， thus achieving a relatively balanced state of the body and inhibiting tumor angiogenesis. As a result， this study， centering on the metabolic remodeling of endothelial cells and ''Yin fire'' theory， elucidated the academic ideas， with the purpose of providing some theoretical support for the intervention of tumor vascularization by Chinese medicine.

Mutation-associated transcripts reconstruct the prognostic features of oral tongue squamous cell carcinoma / 国际口腔科学杂志·英文版

Tongue squamous cell carcinoma is highly malignant and has a poor prognosis. In this study, we aimed to combine whole-genome sequencing, whole-genome methylation, and whole-transcriptome analyses to understand the molecular mechanisms of tongue squamous cell carcinoma better. Oral tongue squamous cell carcinoma and adjacent normal tissues from five patients with tongue squamous cell carcinoma were included as five paired samples. After multi-omics sequencing, differentially methylated intervals, methylated loop sites, methylated promoters, and transcripts were screened for variation in all paired samples. Correlations were analyzed to determine biological processes in tongue squamous cell carcinoma. We found five mutated methylation promoters that were significantly associated with mRNA and lncRNA expression levels. Functional annotation of these transcripts revealed their involvement in triggering the mitogen-activated protein kinase cascade, which is associated with cancer progression and the development of drug resistance during treatment. The prognostic signature models constructed based on WDR81 and HNRNPH1 and combined clinical phenotype-gene prognostic signature models showed high predictive efficacy and can be applied to predict patient prognostic risk in clinical settings. We identified biological processes in tongue squamous cell carcinoma that are initiated by mutations in the methylation promoter and are associated with the expression levels of specific mRNAs and lncRNAs. Collectively, changes in transcript levels affect the prognosis of tongue squamous cell carcinoma patients.

Construction of an epileptic seizure prediction model using a semi-supervised method of generative adversarial and long short term memory network combined with Stockwell transform / 南方医科大学学报

OBJECTIVE@#To propose a semi-supervised epileptic seizure prediction model (ST-WGAN-GP-Bi-LSTM) to enhance the prediction performance by improving time-frequency analysis of electroencephalogram (EEG) signals, enhancing the stability of the unsupervised feature learning model and improving the design of back-end classifier.@*METHODS@#Stockwell transform (ST) of the epileptic EEG signals was performed to locate the time-frequency information by adaptive adjustment of the resolution and retaining the absolute phase to obtain the time-frequency inputs. When there was no overlap between the generated data distribution and the real EEG data distribution, to avoid failure of feature learning due to a constant JS divergence, Wasserstein GAN was used as a feature learning model, and the cost function based on EM distance and gradient penalty strategy was adopted to constrain the unsupervised training process to allow the generation of a high-order feature extractor. A temporal prediction model was finally constructed based on a bi-directional long short term memory network (Bi-LSTM), and the classification performance was improved by obtaining the temporal correlation between high-order time-frequency features. The CHB-MIT scalp EEG dataset was used to validate the proposed patient-specific seizure prediction method.@*RESULTS@#The AUC, sensitivity, and specificity of the proposed method reached 90.40%, 83.62%, and 86.69%, respectively. Compared with the existing semi-supervised methods, the propose method improved the original performance by 17.77%, 15.41%, and 53.66%. The performance of this method was comparable to that of a supervised prediction model based on CNN.@*CONCLUSION@#The utilization of ST, WGAN-GP, and Bi-LSTM effectively improves the prediction performance of the semi-supervised deep learning model, which can be used for optimization of unsupervised feature extraction in epileptic seizure prediction.

AAZ2 induces mitochondrial-dependent apoptosis by targeting PDK1 in gastric cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Drastic surges in intracellular reactive oxygen species (ROS) induce cell apoptosis, while most chemotherapy drugs lead to the accumulation of ROS. Here, we constructed an organic compound, arsenical N-‍(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide (AAZ2), which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer (GC). Mechanistically, by targeting pyruvate dehydrogenase kinase 1 (PDK1), AAZ2 caused metabolism alteration and the imbalance of redox homeostasis, followed by the inhibition of phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway and leading to the activation of B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax)/caspase-9 (Cas9)/Cas3 cascades. Importantly, our in vivo data demonstrated that AAZ2 could inhibit the growth of GC xenograft. Overall, our data suggested that AAZ2 could contribute to metabolic abnormalities, leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.

The occurrence and progress of immune inflammatory response involved in gastroesophageal reflux disease / 中国医师进修杂志

Objective:To investigate the role of immune and inflammatory responses in the pathogenesis of gastroesophageal reflux disease (GERD).Methods:Fifteen patients with GERD who underwent biopsy and histopathology during painless gastroscopy in the digestive endoscopy center of the General Hospital of the PLA from December 2018 to September 2019 were analyzed retrospectively. They were divided into three groups: 6 cases of non erosive reflux disease (NERD), 8 cases of reflux esophagitis (RE) and 1 case of RE with high-grade intraepithelial neoplasia (RE-HIN). HE staining was used to analyze the inflammatory reaction of each group. The expression of cyclooxygenase-2(COX-2), inducible nitric oxide synthase (iNOS), interleukin (IL)-1β, myeloperoxidase (MPO), IL-4, nuclear factor kappa-B(NF-κB), IL-8, reactive oxygen species (ROS-1) were monitored by immunohistochemistry. Chi square test was used to analyze the positive rate of immune and inflammatory indexes in each group.Results:The three groups showed mild and moderate inflammatory cell infiltration, mostly lymphocyte infiltration, and basal cell hyperplasia in 3 cases. There was no significant difference between inflammatory cell infiltration, basal hyperplasia and inflammatory grade in NERD and RE( P>0.05). Immune and inflammatory factors COX-2(positive rate:NERD 4/6, RE4/8, RE-HIN 1/1), iNOS(positive rate:NERD 4/6, RE 3/8, RE-HIN 0), IL-1β(positive rate:NERD 6/6, RE 7/8, RE-HIN 1/1), MPO(positive rate:NERD 4/6, RE 7/8, RE-HIN 1/1), IL-4(positive rate:NERD 3/6, RE 4/8, RE-HIN 0), IL-8(positive rate:NERD 2/6, RE 6/8, RE-HIN 1/1), ROS-1(positive rate:NERD 3/6, RE 1/8, RE-HIN 0) and signal pathway NF- κ B (positive rate:NERD 4/6, RE 8/8, RE-HIN 1/1) were positive in three groups. The expressions of IL-1β, MPO and NF-κB were statistically significant among the three groups ( P<0.05). Conclusions:There is an inflammatory cascade mediated by immune inflammatory factors and mediators in GERD patients, and NF-κB signaling pathway is involved. It provides a basis for finding targets to block immune and inflammatory responses in the later stage to treat GERD.

Associations between indoor volatile organic compounds and nocturnal heart rate variability of young female adults: A panel study / 北京大学学报(医学版)

OBJECTIVE@#To investigate the association between short-term exposure to indoor total volatile organic compounds (TVOC) and nocturnal heart rate variability (HRV) among young female adults.@*METHODS@#This panel study recruited 50 young females from one university in Beijing, China from December 2021 to April 2022. All the participants underwent two sequential visits. During each visit, real time indoor TVOC concentration was monitored using an indoor air quality detector. The real time levels of indoor temperature, relative humidity, noise, carbon dioxide and fine particulate matter were monitored using a temperature and humidity meter, a noise meter, a carbon dioxide meter and a particulate counter, respectively. HRV parameters were measured using a 12-lead Holter. Mixed-effects models were used to evaluate the association between the TVOC and HRV parameters and establish the exposure-response relationships, and two-pollutant models were applied to examine the robustness of the results.@*RESULTS@#The mean age of the 50 female subjects was (22.5±2.3) years, and the mean body mass index was (20.4±1.9) kg/m2. During this study, the median (interquartile range) of indoor TVOC concentrations was 0.069 (0.046) mg/m3, the median (interquartile range) of indoor temperature, relative humidity, carbon dioxide concentration, noise level and fine particulate matter concentration were 24.3 (2.7) ℃, 38.5% (15.0%), 0.1% (0.1%), 52.7 (5.8) dB(A) and 10.3 (21.5) μg/m3, respectively. Short-term exposure to indoor TVOC was associated with significant changes in time-domain and frequency-domain HRV parameters, and the exposure metric for most HRV parameters with the most significant changes was 1 h-moving average. Along with a 0.01 mg/m3 increment in 1 h-moving average concentration of indoor TVOC, this study observed decreases of 1.89% (95%CI: -2.28%, -1.50%) in standard deviation of all normal to normal intervals (SDNN), 1.92% (95%CI: -2.32%, -1.51%) in standard deviation of average normal to normal intervals (SDANN), 0.64% (95%CI: -1.13%, -0.14%) in percentage of adjacent NN intervals differing by more than 50 ms (pNN50), 3.52% (95%CI: -4.30%, -2.74%) in total power (TP), 5.01% (95%CI: -6.21%, -3.79%) in very low frequency (VLF) power, and 4.36% (95%CI: -5.16%, -3.55%) in low frequency (LF) power. The exposure-response curves showed that indoor TVOC was negatively correlated with SDNN, SDANN, TP, and VLF when the concentration exceeded 0.1 mg/m3. The two-pollutant models indicated that the results were generally robust after controlling indoor noise and fine particulate matter.@*CONCLUSION@#Short-term exposure to indoor TVOC was associated with significant negative changes in nocturnal HRV of young women. This study provides an important scientific basis for relevant prevention and control measures.

Ferroptosis-related Recurrence Risk Model Predicts Clinical Outcomes and Immune Infiltration in Glioblastoma / 肿瘤防治研究

Objective To construct a ferroptosis-related glioblastoma (GBM) recurrence risk model and evaluate the prognosis of patients. Methods Differentially expressed genes (DEGs) related to ferroptosis in recurrent GBM were screened by CGGA and FerrDb databases. Key genes were obtained by Lasso regression. Then, nomogram was constructed according to the key risk genes, and the prediction efficiency was verified using the TCGA database. GO, KEGG, and GSEA databases were used in exploring the mechanism of prognosis. ESTIMATE and TIMER were used in studying tumor immune infiltration and the expression of immune check points. Results WWTR1, PLIN2, and BID were important prognostic factors for GBM recurrence. The nomogram was constructed according to gender and age, and the observed values were in good agreement with the predicted values. The AUC values were 0.65 (1 year), 0.66 (3 years), and 0.63 (5 years) for CGGA and 0.68 (1 year), 0.76 (3 years), and 0.79 (5 years) for TCGA. Epithelial mesenchymal transition, KRAS pathway, and inflammatory response were significantly upregulated in the high-risk subtypes (P < 0.05). Immune cell infiltration was lower (P < 0.05). Risk score was positively correlated with the expression of immunosuppression check points. Conclusion Ferroptosis-related genes WWTR1, PLIN2, and BID can be used in constructing a nomogram with good predictive performance. These risk genes may affect prognosis through tumor-infiltrating immune cells and immune check points.

Analysis of spontaneous nystagmus and the frequency characteristics of affected semicircular canals in patients with vestibular neuritis / 中华内科杂志

Objective: To investigate the spontaneous nystagmus (SN) and the frequency characteristics of affected semicircular canals in patients with vestibular neuritis (VN). Methods: This is a cross-sectional study. A total of 61 patients with VN admitted to the Department of Neurology of Shanxi Bethune Hospital from June 2020 to October 2021, 39 were male and 22 were female, with a mean age of (46±13) years old and male to female ratio of 1.77∶1. According to SN characteristics, 61 patients were divided into non-nystagmus group(nSN), horizontal nystagmus group(hSN) and horizontal-torsional nystagmus group (htSN). Clinical data were collected, and SN, unilateral weakness (UW), directional preponderance (DP), and video head impulse test (vHIT) gain were used as observation indicators. Statistical analysis by SPSS23.0 software. Normal distributed quantitative data (age, semicircular canal gain, SN intensity) were expressed by x¯±s, non-normal distributed quantitative data (disease course, UW, DP) were expressed by M(Q1,Q3), qualitative data were expressed by rate and composition ratio, difference analysis by one-way ANOVA, rank sum test, Chi-square test or Fisher's exact probability method, considered by P value<0.05. Results: (1)The disease course of nSN, hSN and htSN was 7.0 (4.0, 12.5), 6.0 (3.5, 11.5), and 3.0 (2.0, 6.5) days respectively, and there were statistical differences (χ2=7.31,P=0.026).(2)The horizontal nystagmus intensity of htSN was (16.8±8.6)°/s, which was significantly higher than that of (9.8±4.7)°/s in hSN (t=3.71, P<0.001). There was no significant difference in the positive rate of UW between the three groups (P=0.690), and there was a significant difference in the positive rate of DP in the three groups (χ2=12.23, P=0.002). The horizontal nystagmor intensity in the htSN was positively correlated with the vertical nystagmus intensity (r=0.59, P=0.001).(3)The gain of the affected horizontal canal of the three groups was statistically different (F=8.28, P=0.001), and the gain of the horizontal canal of hSN and htSN was significantly lower than that of nSN (t=2.74, P=0.008; t=4.05, P<0.001); The gain of the affected anterior canal in the three groups was statistically different (F=5.32, P=0.008). The gain of the anterior canal in both nSN and hSN was significantly higher than that in htSN (t=3.09, P=0.003; t=2.15, P=0.036). The horizontal canal gain of htSN is positively correlated with the anterior canal gain (r=0.74, P<0.001).(4)The affected semicircular canals in the two groups with no-vertical-component nystagmus (nSN and hSN) and the htSN were counted. The composition ratio of the affected semicircular canals in the two groups was different (χ2=8.34, P=0.015). Conclusion: The occurrence of SN in patients with VN is related to many factors, such as the disease course, low and high frequencies, and the severity of the condition in the affected semicircular canal.

Epidemiological characteristics of cardio-metabolic risk factors among children and adolescents aged 7-17 years in 4 provinces of China / 中华流行病学杂志

Objective: This study aimed to investigate the epidemiological characteristics of cardio-metabolic risk factors among children and adolescents aged 7-17 years in (Hebei, Zhejiang, Shaanxi, Hunan) 4 provinces of China and the influence of demographic and economic characteristics on them. Methods: A total of 1 747 children and adolescents aged 7-17 from a Community-based Cohort Study on Nervous System Disease in 2018 were selected. High waist circumference, central obesity, elevated TG, elevated TC, elevated LDL-C, decreased HDL-C, elevated blood pressure, elevated blood glucose, and clustering of risk factors was analyzed. χ2 test was used for univariate analysis, multivariate logistic regression was used to analyze the correlation between demographic and economic factors and risk factors, and the Cochran-Armitage trend test was used for trend analysis. Results: The detection rates of high waist circumference, decreased HDL-C, elevated blood pressure, elevated TG, elevated blood glucose, central obesity, elevated TC, and elevated LDL-C were 29.08%, 15.28%, 13.17%, 13.05%, 11.79%, 7.33%, 6.53%, and 5.15%, respectively. The rate of clustering of risk factors was 18.37%. Multivariate logistic regression analysis showed that the risk of high waist circumference in girls was higher than that in boys (OR=1.67, 95%CI: 1.26-2.22), and the risk of elevated blood glucose and clustering of risk factors was lower than that in boys (OR=0.69, 95%CI: 0.49-0.99; OR=0.72, 95%CI: 0.53-0.99). The risk of high waist circumference, decreased HDL-C, and clustering of risk factors in 13-17 years old group was higher than that in the 7-year-olds group (OR=2.24, 95%CI: 1.65-3.04; OR=1.59, 95%CI: 1.20-2.11; OR=1.75, 95%CI: 1.26-2.44), but the risk of central obesity was lower (OR=0.54, 95%CI: 0.37-0.78). The risk of elevated TC, elevated TG, and decreased HDL-C in children and adolescents in southern was higher than that in northern parts of China (OR=1.88, 95%CI: 1.25-2.83; OR=1.61, 95%CI: 1.17-2.22; OR=1.55, 95%CI: 1.19-2.04), but the risk of high waist circumference and central obesity was lower than that in northern China (OR=0.57, 95%CI: 0.43-0.75; OR=0.62, 95%CI: 0.42-0.90). The risk of decreased HDL-C in rural children and adolescents was higher than in urban children and adolescents (OR=1.36, 95%CI: 1.02-1.83). The risk of multiple risk factors increased with the increase in average monthly household income per capita and BMI level. Conclusions: High waist circumference, decreased HDL-C and elevated blood pressure were prominent cardio-metabolic risk factors among children and adolescents aged 7-17 years in 4 provinces of China in 2018. The region, average monthly household income per capita, and BMI were the main influencing factors of cardio-metabolic risk factors.

Assessment of the local blood supply when femoral neck fracture occurs:advances in the anatomy research and its clinical application / 中国骨伤

The stability of internal fixation of femoral neck fractures can be obtained through surgical techniques, the configuration of screws and bone grafting, etc. However, the blood supply injury caused by fractures could not be completely reversed by the current medical management. Hence, the comprehensive evaluation of the residual blood supply of the femoral neck, to perioperatively avoid further iatrogenic injury, has become a hotspot. The anatomy of the extraosseous blood supply of the femoral neck has been widely reported, while its clinical application mostly involved the assessment of the medial circumflex femoral artery and retinacular arteries. However, further studies are needed to explore the prognosis of patients with these artery injuries, with different degrees, caused by femoral neck fractures. Direct observations of nutrient foramina in vivo are not possible with current clinical technologies, but it is possible to make reasonable preoperative planning to avoid subsequent femoral head necrosis based on the distribution features of nutrient foramina. The anatomy and clinical application studies of the intraosseous blood supply focused on the junction area of the femoral head and neck to probe the mechanism of femoral head necrosis. Thus, the intraosseous blood supply of other regions in the femoral neck remains to be further investigated. In addition, a blood supply evaluation system based on a three-level structure, extraosseous blood vessels, nutrient foramina, and intraosseous vascular network, could be explored to assist in the treatment of femoral neck fractures.

A study on the Charlson comorbidity index and health-related quality of life in the middle-aged and elderly osteoporosis population / 中国骨伤

OBJECTIVE@#To explore the characteristics of comorbidities in patients with osteoporosis(OP) and factors associated health-related quality of life, so as to provide decision-making reference for improving the ability of disease co-prevention and co-treatment and the patient's life-cycle quality of life.@*METHODS@#From November 2017 to July 2018, clinical information and biological samples from residents in 10 communities in Chaoyang District and Fengtai Distric of Beijing were collected, and bone density testing was conducted. Based on the Charlson comorbidity index (CCI), the comorbidity of the population was quantified, and grouped according to factors such as gender, age, and the differences between the groups were explored. Combined with the clinical information of patients, the difference characteristics of comorbidity and non-comorbidity population were analyzed. Pearson/Spearman correlation analysis and binary Logistic regression analysis were used to explore the factors affecting the health-related quality of life in patients with OP.@*RESULTS@#Among the 521 OP patients, 121 patients had no comorbidities, and there were 153, 106, 65, and 30 patients with one, two, three, and four comorbidities, respectively, 46 patients with 5 or more kinds of comorbidites. Hypertension was the most common comorbidity in OP patients, accounting for 21.60%;followed by hyperlipidemia, accounting for 13.51%. The most common combination of the two diseases was hypertension plus hyperlipidemia (64 cases, 12.28%). Through the analysis of differences between age groups, it was found that the older patients, showed higher the CCI, and the difference between groups was statistically significant(Z=1.93, P=0.05). There were significant differences in the total EQ-5D score and the dimensions of anxiety and depression between patients with comorbidities (CCI≠0) and non-comorbidities (CCI=0) (Z=-2.67, P=0.01;Z=-2.44, P=0.02). Correlation analysis found that CCI, history of fracture, history of falls, hip bone mineral density T value and parathyroid hormone were all related to the health-related quality of life in OP patients (P<0.05). Binary Logistic regression analysis suggested that the right hip bone mineral density T value (P=0.02), CCI (P=0.01), fracture history (P=0.03) and fall history (P=0.01) were the risk factors that affect the health-related quality of life in OP patients.@*CONCLUSION@#The burden of comorbidities among middle-aged and elderly OP populations in Beijing is relatively heavy, and the health management of such populations should be further strengthened, specifically the combination of multiple comorbidities should be given high priority. Comorbid factors are of great importance for the diagnosis and treatment strategy of OP patients, which could further improve the quality of life.

Influence of antimicrobial peptide biofunctionalized TiO2 nanotubes on the biological behavior of human keratinocytes and its antibacterial effect / 中华口腔医学杂志

Objective: To fabricate TiO2 nanotube material functionalized by antimicrobial peptide LL-37, and to explore its effects on biological behaviors such as adhesion and migration of human keratinocytes (HaCaT) and its antibacterial properties. Methods: The TiO2 nanotube array (NT) was constructed on the surface of polished titanium (PT) by anodization, and the antimicrobial peptide LL-37 was loaded on the surface of TiO2 nanotube (LL-37/NT) by physical adsorption. Three samples were selected by simple random sampling in each group. Surface morphology, roughness, hydrophilicity and release characteristics of LL-37 of the samples were analyzed with a field emission scanning electron microscope, an atomic force microscope, a contact angle measuring device and a microplate absorbance reader. HaCaT cells were respectively cultured on the surface of three groups of titanium samples. Each group had 3 replicates. The morphology of cell was observed by field emission scanning electron microscope. The number of cell adhesion was observed by cellular immunofluorescence staining. Cell counting kit-8 (CCK-8) assay was used to detect cell proliferation. Wound scratch assay was used to observe the migration of HaCaT. The above experiments were used to evaluate the effect of each group on the biological behavior of HaCaT cells. To evaluate their antibacterial effects, Porphyromonas gingivalis (Pg) was respectively inoculated on the surface of three groups of titanium samples. Each group had 3 replicates. The morphology of bacteria was observed by field emission scanning electron microscope. Bacterial viability was determined by live/dead bacterial staining. Results: A uniform array of nanotubes could be seen on the surface of titanium samples in LL-37/NT group, and the top of the tube was covered with granular LL-37. Compared with PT group [the roughness was (2.30±0.18) nm, the contact angle was 71.8°±1.7°], the roughness [(20.40±3.10) and (19.10±4.11) nm] and hydrophilicity (the contact angles were 22.4°±3.1° and 25.3°±2.2°, respectively) of titanium samples increased in NT and LL-37/NT group (P<0.001). The results of in vitro release test showed that the release of antimicrobial peptide LL-37 was characterized by early sudden release (1-4 h) and long-term (1-7 d) slow release. With the immunofluorescence, more cell attachment was found on NT and LL-37/NT than that on PT at the first 0.5 and 2.0 h of culture (P<0.05). The results of CCK-8 showed that there was no significant difference in the proliferation of cells among groups at 1, 3 and 5 days after culture. Wound scratch assay showed that compared with PT and NT group, the cell moved fastest on the surface of titanium samples in LL-37/NT group at 24 h of culture [(96.4±4.9)%] (F=35.55, P<0.001). A monolayer cells could be formed and filled with the scratch in 24 h at LL-37/NT group. The results of bacterial test in vitro showed that compared with the PT group, the bacterial morphology in the NT and LL-37/NT groups was significantly wrinkled, and obvious bacterial rupture could be seen on the surface of titanium samples in LL-37/NT group. The results of bacteria staining showed that the green fluorescence intensity of titanium samples in LL-37/NT group was the lowest in all groups (F=66.54,P<0.001). Conclusions: LL-37/NT is beneficial to the adhesion and migration of HaCaT cells and has excellent antibacterial properties, this provides a new strategy for the optimal design of implant neck materials.

Correlation analysis and benchmark dose study on bone metabolic biochemical index of low doses of exposed hydrogen fluoride workers / 中华劳动卫生职业病杂志

Objective: To analyze correlation of occupational hydrogen fluoride exposure to low doses of bone metabolism index through occupational epidemiological investigation and benchmark dose calculation. Methods: In May 2021, using cluster sampling method, 237 workers exposed to hydrogen fluoride in a company were selected as the contact group, and 83 workers not exposed to hydrogen fluoride in an electronics production company were selected as the control group. The external exposure dose and urinary fluoride concentration, blood and urine biochemical indicators of the workers was measured.The relationship between external dose and internal dose of hydrogen fluoride was analyzed. The external dose, urinary fluoride was used as exposure biomarkers, while serum osteocalcin (BGP), serum alkaline phosphatase (AKP) and urinary hydroxyproline (HYP) were used as effect biomarkers for bone metabolism of hydrogen fluoride exposure. The benchmark dose calculation software (BMDS1.3.2) was used to calculate benchmark dose (BMD) . Results: Urine fluoride concentration in the contact group was correlated with creatinine-adjusted urine fluoride concentration (r=0.69, P=0.001). There was no significant correlation between the external dose of hydrogen fluoride and urine fluoride in the contact group (r=0.03, P=0.132). The concentrations of urine fluoride in the contact group and the control group were (0.81±0.61) and (0.45±0.14) mg/L, respectively, and the difference between the two groups was statistically significant (t=5.01, P=0.025). Using BGP, AKP and HYP as effect indexes, the urinary BMDL-05 values were 1.28, 1.47 and 1.08 mg/L, respectively. Conclusion: Urinary fluoride can sensitively reflect the changes in the effect indexes of biochemical indexes of bone metabolism. BGP and HYP can be used as early sensitive effect indexes of occupational hydrogen fluoride exposure.