Construction of a Prognostic Model of Multiple Myeloma Based on Metabolism-Related Genes / 中国实验血液学杂志

OBJECTIVE@#To screen the prognostic biomarkers of metabolic genes in patients with multiple myeloma (MM), and construct a prognostic model of metabolic genes.@*METHODS@#The histological database related to MM patients was searched. Data from MM patients and healthy controls with complete clinical information were selected for analysis.The second generation sequencing data and clinical information of bone marrow tissue of MM patients and healthy controls were collected from human protein atlas (HPA) and multiple myeloma research foundation (MMRF) databases. The gene set of metabolism-related pathways was extracted from Molecular Signatures Database (MSigDB) by Perl language. The biomarkers related to MM metabolism were screened by difference analysis, univariate Cox risk regression analysis and LASSO regression analysis, and the risk prognostic model and Nomogram were constructed. Risk curve and survival curve were used to verify the grouping effect of the model. Gene set enrichment analysis (GSEA) was used to study the difference of biological pathway enrichment between high risk group and low risk group. Multivariate Cox risk regression analysis was used to verify the independent prognostic ability of risk score.@*RESULTS@#A total of 8 mRNAs which were significantly related to the survival and prognosis of MM patients were obtained (P<0.01). As molecular markers, MM patients could be divided into high-risk group and low-risk group. Survival curve and risk curve showed that the overall survival time of patients in the low-risk group was significantly better than that in the high risk group (P<0.001). GSEA results showed that signal pathways related to basic metabolism, cell differentiation and cell cycle were significantly enriched in the high-risk group, while ribosome and N polysaccharide biosynthesis signaling pathway were more enriched in the low-risk group. Multivariate Cox regression analysis showed that the risk score composed of the eight metabolism-related genes could be used as an independent risk factor for the prognosis of MM patients, and receiver operating characteristic curve (ROC) showed that the molecular signatures of metabolism-related genes had the best predictive effect.@*CONCLUSION@#Metabolism-related pathways play an important role in the pathogenesis and prognosis of patients with MM. The clinical significance of the risk assessment model for patients with MM constructed based on eight metabolism-related core genes needs to be confirmed by further clinical studies.

Comparison of the predictive value of anthropometric indicators for the risk of benign prostatic hyperplasia in southern China / 亚洲男科学杂志(英文版)

This study aimed to compare the predictive value of six selected anthropometric indicators for benign prostatic hyperplasia (BPH). Males over 50 years of age who underwent health examinations at the Health Management Center of the Second Xiangya Hospital, Central South University (Changsha, China) from June to December 2020 were enrolled in this study. The characteristic data were collected, including basic anthropometric indices, lipid parameters, six anthropometric indicators, prostate-specific antigen, and total prostate volume. The odds ratios (ORs) with 95% confidence intervals (95% CIs) for all anthropometric parameters and BPH were calculated using binary logistic regression. To assess the diagnostic capability of each indicator for BPH and identify the appropriate cutoff values, receiver operating characteristic (ROC) curves and the related areas under the curves (AUCs) were utilized. All six indicators had diagnostic value for BPH (all P ≤ 0.001). The visceral adiposity index (VAI; AUC: 0.797, 95% CI: 0.759-0.834) had the highest AUC and therefore the highest diagnostic value. This was followed by the cardiometabolic index (CMI; AUC: 0.792, 95% CI: 0.753-0.831), lipid accumulation product (LAP; AUC: 0.766, 95% CI: 0.723-0.809), waist-to-hip ratio (WHR; AUC: 0.660, 95% CI: 0.609-0.712), waist-to-height ratio (WHtR; AUC: 0.639, 95% CI: 0.587-0.691), and body mass index (BMI; AUC: 0.592, 95% CI: 0.540-0.643). The sensitivity of CMI was the highest (92.1%), and WHtR had the highest specificity of 94.1%. CMI consistently showed the highest OR in the binary logistic regression analysis. BMI, WHtR, WHR, VAI, CMI, and LAP all influence the occurrence of BPH in middle-aged and older men (all P ≤ 0.001), and CMI is the best predictor of BPH.

Effects of manipulator operation task and troubleshooting task on blood pressure indexes of oceanauts / 中华劳动卫生职业病杂志

Objective: To explore the characteristics and rules of blood pressure changes in oceanauts during simulated operation of manipulator and troubleshooting tasks with different difficulty. Methods: In July 2020, 8 deep-sea manned submersible oceanauts, 6 males and 2 females, were selected as objects. In the 1∶1 model of Jiaolong deep-sea manned submersible, the oceanauts performed manipulator operation tasks and troubleshooting tasks with different difficulties, measured the continuous blood pressure of the oceanauts, filled in the NASA Task Load Index (NASA-TLX scale) after the completion of a single mission, and the changes of systolic pressure (SBP), diastolic pressure (DBP), mean arterial pressure (MAP) and mental workload were analyzed. Results: In a single task, the SBP, DBP and MAP of the oceanauts increased first and then decreased. The blood pressure values at the third minute were significantly lower than those at the first minute (P<0.01), and those at the fifth minute were significantly higher than those at the third minute (P<0.01). When performing the same task, compared with the quiet state, SBP, DBP and MAP increased when the oceanauts performed low difficulty, high difficulty, high difficulty+2-back manipulator operation task and troubleshooting task (P<0.05). When the task difficulty was the same, the SBP and MAP of oceanauts performing manipulator operation tasks were higher than those of oceanauts performing troubleshooting tasks (P<0.05). Compared with low difficulty tasks, the scores of NASA-TLX scale for oceanauts performing high difficulty manipulator operationtasks were significantly higher (P<0.05). Compared with the low difficulty task and high difficulty task, the scale score of the high difficulty+2-back troubleshooting task was significantly higher (P<0.05). When the task difficulty was the same, the scale scores of low difficulty and high difficulty manipulator operation tasks were significantly higher than those of troubleshooting tasks (P<0.05). SBP, DBP, MAP of No. 1, No. 3, No. 4, No. 5, and No. 7 oceanauts (all of whom had 6 years of diving) were positively correlated with NASA-TLX scale scores (r>0.8, P<0.05) . Conclusion: In the process of manned deep-sea diving, when the oceanauts perform manipulator operation tasks and troubleshooting tasks, with the increase of task difficulty, the mental load of oceanauts increases, and the blood pressure index increases significantly in a short time. At the same time, improving the proficiency of operation can reduce the variation range of blood pressure indexes. Blood pressure can be used as an effective reference to evaluate the difficulty of operation and guide scientific training.

Hydroxysafflor yellow A inhibits proliferation, migration, and chemoresistance of colorectal cancer cells through Akt/mTOR-autophagy pathway / 中国中药杂志

In recent years, the clinical treatment of colorectal cancer(CRC) has made great progress, but chemoresistance is still one of the main reasons for reducing the survival rate of patients with colorectal cancer. Therefore, ameliorating chemotherapy resis-tance is an urgent problem to be solved. The purpose of this study was to investigate the regulatory role and related molecular mechanisms of hydroxysafflor yellow A(HSYA) in colorectal cancer cell proliferation, migration, and 5-fluorouracil(5-FU) chemoresistance. In this study, HCT116 and HT-29 cells were used as research subjects. Firstly, methyl thiazolyl tetrazolium(MTT) assay and colony formation assay were used to detect and analyze the effect of HSYA on the proliferation of CRC cells. Secondly, the effect of HSYA on the cell cycle in CRC cells was analyzed by cell cycle assay. Furthermore, the effect of HSYA on the migration of CRC cells was analyzed by wound-healing assay and Transwell assay. Based on the above, the influences of HSYA on 5-FU chemoresistance of CRC cells and related molecular mechanisms were explored and analyzed. The results showed that HSYA significantly inhibited the proliferation and migration of CRC cells, and arrested the cell cycle in G_0/G_1 phase. In addition, HSYA significantly ameliorated the chemoresistance of CRC cells to 5-FU. The results of acridine orange staining and Western blot showed that the autophagy activity of CRC cells in the HSYA and 5-FU combined treatment group was significantly higher than that in the 5-FU single drug treatment group. As compared with the 5-FU single drug treatment group, the phosphorylation levels of protein kinase B(Akt) and mammalian target of rapamycin(mTOR) in the HSYA and 5-FU combined treatment group were significantly reduced, indicating that the Akt/mTOR signaling pathway in the combined treatment group was down-regulated in CRC cells. In conclusion, HSYA may upregulate autophagy activity through the Akt/mTOR signaling pathway, thereby inhibiting the proliferation and migration of CRC cells and ameliorating the chemoresistance to 5-FU.

Mechanism of active ingredients in Periploca forrestii compound against rheumatoid arthritis based on integrative metabolomics and network pharmacology / 中国中药杂志

In this study, an ultra-performance liquid chromatography-quadrupole time-of-flight high resolution mass spectrometer(UPLC-Q-TOF-HRMS) was used to investigate the effects of the active ingredients in Periploca forrestii compound on spleen metabolism in rats with collagen-induced arthritis(CIA), and its potential anti-inflammatory mechanism was analyzed by network pharmacology. After the model of CIA was successfully established, the spleen tissues of rats were taken 28 days after administration. UPLC-Q-TOF-HRMS chromatograms were collected and analyzed by principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and MetPA. The results showed that as compared with the blank control group, 22 biomarkers in the spleen tissues such as inosine, citicoline, hypoxanthine, and taurine in the model group increased, while 9 biomarkers such as CDP-ethanolamine and phosphorylcholine decreased. As compared with the model group, 21 biomarkers such as inosine, citicoline, CDP-ethanolamine, and phosphorylcholine were reregulated by the active ingredients in P. forrestii. Seventeen metabolic pathways were significantly enriched, including purine metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism. Network pharmacology analysis found that purine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism played important roles in the pathological process of rheumatoid arthritis. This study suggests that active ingredients in P. forrestii compound can delay the occurrence and development of inflammatory reaction by improving the spleen metabolic disorder of rats with CIA. The P. forrestii compound has multi-target and multi-pathway anti-inflammatory mechanism. This study is expected to provide a new explanation for the mechanism of active ingredients in P. forrestii compound against rheumatoid arthritis.

Research Progress in Pathogenesis of Hypertension in Acute Intermittent Porphyria / 中国医学科学院学报

Acute intermittent porphyria (AIP) has complicated clinical manifestations and is often accompanied by hypertension.AIP may cause hypertension through adrenergic effect,heme deficiency,inflammation,inappropriate secretion of antidiuretic hormone,toxicity of delta-aminolevulinic acid(ALA,aporphyrin precursor),and elevated serum glucose level.The prevention and treatment strategies for AIP accompanied with hypertension mainly include the controlling of porphyria attacks,application of antihypertensive drugs,lifestyle intervention,and management of latent AIP patients.

Preliminary Results of Single-cell Transcriptome Sequencing in Renal Arterial Lesions of Takayasu Arteritis / 中国医学科学院学报

Objective To explore the preliminary application of single-cell RNA sequencing (scRNA-seq) in the renal arterial lesions in Takayasu arteritis (TA) patients. Methods This study included 2 TA patients with renal artery stenosis treated by bypass surgery in the Department of Vascular Surgery,Beijing Hospital.The obtained 2 renal artery samples were digested with two different protocols (GEXSCOPE kit and self-made digestion liquid) before scRNA-seq and bioinformatics analysis. Results A total of 2920 cells were obtained for further analysis.After unbiased cluster analysis,2 endothelial cell subsets,2 smooth muscle cell subsets,1 fibroblast subset,2 mononuclear macrophage subsets,1 T cell subset,and 1 undefined cell subset were identified.Among them,the two subsets of smooth muscle cells were contractile and secretory,respectively.The results of scRNA-seq indicated that enzymatic hydrolysis with GEXSCOPE kit produced a large number of endothelial cells (57.46%) and a small number of immune cells (13.21%).However,immune cells (34.64%) were dominant in the cells obtained by enzymatic hydrolysis with self-made digestive liquid. Conclusion scRNA-seq can be employed to explore the cellular heterogeneity of diseased vessels in TA patients.Different enzymatic digestion protocols may impact the proportion of different cells.

Drug resistance and genomic characteristics of a strain of O139 Vibrio cholerae isolated from human bloodstream infection / 中华预防医学杂志

Objective: To analyze the drug resistance and genomic characteristics of a strain of serogroup O139 Vibrio cholerae producing cholera toxin isolated from the bloodstream of a person with bacteremia. Methods: The broth dilution method and automatic drug sensitivity analyzer were used to determine the antibiotic sensitivity of the strain. The complete genome sequence of the strain was obtained by using second-generation gene sequencing and nanopore sequencing. BLAST software was used for comparison and analysis with CARD, Resfinder, ISfinder, VFDB, and other databases. The drug-resistant genes, insertion sequences and virulence genes carried by the strain were identified. MEGA 5.1 software was used to construct a genetic phylogenetic tree based on the core genomic single nucleotide polymorphisms. Results: V. cholerae SH400, as the toxigenic strain, carried multiple virulence-related genes and four virulence islands. The strain was resistant to streptomycin, tetracycline and cotrimoxazole, carrying corresponding drug-resistant genes. The strain also carried IncA/C plasmid with the size of 172914 bp and contained 10 drug-resistant genes. Combined with the genomic evolutionary relationship, this study found that the drug-resistant genes and drug-resistant plasmids carried among strains showed certain aggregation. The traditional ST type of strain SH400 was ST69, and the cgMLST type was a new type highly similar to cgST-252. Conclusion: This strain of serogroup O139 V. cholerae carries the ctxAB gene, multiple drug-resistant genes and IncA/C plasmid, and there are multiple drug-resistant islands.

Five new terpenoids from Viburnum odoratissimum var. sessiliflorum / 中国天然药物

Five new terpenoids, including two vibsane-type diterpenoids (1, 2) and three iridoid allosides (3-5), together with eight known ones, were isolated from the leaves and twigs of Viburnum odoratissimum var.sessiliflorum. Their planar structures and relative configurations were determined by spectroscopic methods, especially 2D NMR techniques. The sugar moieties of the iridoids were confirmed as β-D-allose by GC analysis after acid hydrolysis and acetylation. The absolute configurations of neovibsanin Q (1) and dehydrovibsanol B (2) were determined by quantum chemical calculation of their theoretical electronic circular dichroism (ECD) spectra and Rh2(OCOCF3)4-induced ECD analysis. The anti-inflammatory activities of compounds 1, 3, 4, and 5 were evaluated using an LPS-induced RAW264.7 cell model. Compounds 3suppressed the release of NO in a dose-dependent manner, with an IC50 value of 55.64 μmol·L-1. The cytotoxicities of compounds 1-5 on HCT-116 cells were assessed and the results showed that compounds 2 and 3 exhibited moderate inhibitory activities with IC50 values of 13.8 and 12.3 μmol·L-1, respectively.

Projection-Specific Heterogeneity of the Axon Initial Segment of Pyramidal Neurons in the Prelimbic Cortex / 神经科学通报·英文版

The axon initial segment (AIS) is a highly specialized axonal compartment where the action potential is initiated. The heterogeneity of AISs has been suggested to occur between interneurons and pyramidal neurons (PyNs), which likely contributes to their unique spiking properties. However, whether the various characteristics of AISs can be linked to specific PyN subtypes remains unknown. Here, we report that in the prelimbic cortex (PL) of the mouse, two types of PyNs with axon projections either to the contralateral PL or to the ipsilateral basal lateral amygdala, possess distinct AIS properties reflected by morphology, ion channel expression, action potential initiation, and axo-axonic synaptic inputs from chandelier cells. Furthermore, projection-specific AIS diversity is more prominent in the superficial layer than in the deep layer. Thus, our study reveals the cortical layer- and axon projection-specific heterogeneity of PyN AISs, which may endow the spiking of various PyN types with exquisite modulation.

Application of a low copper diet guidance based on food exchange portions in children with hepatolenticular degeneration / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy of a low-copper diet guidance based on food exchange portions in children with hepatolenticular degeneration.@*METHODS@#A self-controlled study was conducted from July 2021 to June 2022, including 30 children under the age of 18 who were diagnosed with hepatolenticular degeneration and poorly controlled with a low-copper diet. During the medical visit, personalized low-copper diet guidance was provided to the children and their parents using a copper-containing food exchange table and a copper food exchange chart. During home care, compliance with the low-copper diet of the children was improved by recording dietary diaries and conducting regular follow-ups. The changes in 24-hour urine copper level, liver function indicators, and the low-copper diet knowledge of the children's parents were observed before and after the intervention, with no change in the original drug treatment.@*RESULTS@#After 8, 16, and 24 weeks of intervention, the 24-hour urine copper level decreased significantly compared to before intervention (P<0.05). When compared to 8-week intervention, the urine copper level decreased significantly after 16 and 24 weeks of intervention. The 24-hour urine copper level after 24 weeks of intervention decreased significantly compared to 16 weeks of intervention (P<0.05).After 24 weeks of intervention, the alanine aminotransferase and aspartate aminotransferase levels decreased significantly compared to before intervention (P<0.05). Additionally, in 16 of the cases (53%), alanine aminotransferase and aspartate aminotransferase returned to normal levels. Following 8 weeks of intervention, the low-copper diet knowledge of the children's parents increased significantly (P<0.05).@*CONCLUSIONS@#A low-copper diet guidance based on food exchange portions can effectively decrease the urine copper level and improve liver function in children with hepatolenticular degeneration. Furthermore, it can increase the low-copper diet knowledge of the children's parents.

Effect of SAM junctional tourniquet on respiration when applied in the axilla: A swine model / 中华创伤杂志(英文版)

PURPOSE@#SAM junctional tourniquet (SJT) has been applied to control junctional hemorrhage. However, there is limited information about its safety and efficacy when applied in the axilla. This study aims to investigate the effect of SJT on respiration when used in the axilla in a swine model.@*METHODS@#Eighteen male Yorkshire swines, aged 6-month-old and weighing 55 - 72 kg, were randomized into 3 groups, with 6 in each. An axillary hemorrhage model was established by cutting a 2 mm transverse incision in the axillary artery. Hemorrhagic shock was induced by exsanguinating through the left carotid artery to achieve a controlled volume reduction of 30% of total blood volume. Vascular blocking bands were used to temporarily control axillary hemorrhage before SJT was applied. In Group I, the swine spontaneously breathed, while SJT was applied for 2 h with a pressure of 210 mmHg. In Group II, the swine were mechanically ventilated, and SJT was applied for the same duration and pressure as Group I. In Group III, the swine spontaneously breathed, but the axillary hemorrhage was controlled using vascular blocking bands without SJT compression. The amount of free blood loss was calculated in the axillary wound during the 2 h of hemostasis by SJT application or vascular blocking bands. After then, a temporary vascular shunt was performed in the 3 groups to achieve resuscitation. Pathophysiologic state of each swine was monitored for 1 h with an infusion of 400 mL of autologous whole blood and 500 mL of lactated ringer solution. Tb and T0 represent the time points before and immediate after the 30% volume-controlled hemorrhagic shock, respectively. T30, T60, T90 and T120, denote 30, 60, 90, and 120 min after T0 (hemostasis period), while T150, and T180 denote 150 and 180 min after T0 (resuscitation period). The mean arterial pressure and heart rate were monitored through the right carotid artery catheter. Blood samples were collected at each time point for the analysis of blood gas, complete cell count, serum chemistry, standard coagulation tests, etc., and thromboelastography was conducted subsequently. Movement of the left hemidiaphragm was measured by ultrasonography at Tb and T0 to assess respiration. Data were presented as mean ± standard deviation and analyzed using repeated measures of two-way analysis of variance with pairwise comparisons adjusted using the Bonferroni method. All statistical analyses were processed using GraphPad Prism software.@*RESULTS@#Compared to Tb, a statistically significant increase in the left hemidiaphragm movement at T0 was observed in Groups I and II (both p < 0.001). In Group III, the left hemidiaphragm movement remained unchanged (p = 0.660). Compared to Group I, mechanical ventilation in Group II significantly alleviated the effect of SJT application on the left hemidiaphragm movement (p < 0.001). Blood pressure and heart rate rapidly increased at T0 in all three groups. Respiratory arrest suddenly occurred in Group I after T120, which required immediate manual respiratory assistance. PaO2 in Group I decreased significantly at T120, accompanied by an increase in PaCO2 (both p < 0.001 vs. Groups II and III). Other biochemical metabolic changes were similar among groups. However, in all 3 groups, lactate and potassium increased immediately after 1 min of resuscitation concurrent with a drop in pH. The swine in Group I exhibited the most severe hyperkalemia and metabolic acidosis. The coagulation function test did not show statistically significant differences among three groups at any time point. However, D-dimer levels showed a more than 16-fold increase from T120 to T180 in all groups.@*CONCLUSION@#In the swine model, SJT is effective in controlling axillary hemorrhage during both spontaneous breathing and mechanical ventilation. Mechanical ventilation is found to alleviate the restrictive effect of SJT on thoracic movement without affecting hemostatic efficiency. Therefore, mechanical ventilation could be necessary before SJT removal.

Analysis of clinical features and PAK1 gene variant in a child with epilepsy and global developmental delay / 中华医学遗传学杂志

OBJECTIVE@#To investigate the clinical phenotype and genetic basis of a child with epilepsy and global developmental delay.@*METHODS@#A child with epilepsy and global developmental delay who had visited West China Second University Hospital, Sichuan University on April 1, 2021 was selected as the study subject. Clinical data of the child were reviewed. Genomic DNA was extracted from peripheral blood samples of the child and his parents. Whole exome sequencing (WES) was carried out for the child, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. A literature review was also carried out by searching databases such as Wanfang data knowledge service platform, China National Knowledge Infrastructure, PubMed, ClinVar and Embase to summarize the clinical phenotypes and genotypes of the affected children.@*RESULTS@#The child was a 2-year-and-2-month-old male with epilepsy, global developmental delay and macrocephaly. Results of WES showed that the child has harbored a c.1427T>C variant of the PAK1 gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. Only one similar case had been recorded by the dbSNP, OMIM, HGMD, and ClinVar databases. No frequency for this variant among Asian population was available in the ExAC, 1000 Genomes, and gnomAD databases. Prediction with IFT, PolyPhen-2, LRT, Mutation Taster, and FATHMM online software suggested that this variant is deleterious to the function of encoded protein. Based on the Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics (ACMG), the PAK1 gene c.1427T>C variant was determined to be likely pathogenic.@*CONCLUSION@#The PAK1 gene c.1427T>C variant probably underlay the epilepsy and global developmental delay in this child, which has provided a reference for the clinical diagnosis and genetic counseling in children with similar disorders.

Progress of injection sites of local infiltration analgesia in total knee arthroplasty / 中国修复重建外科杂志

OBJECTIVE@#To review the research progress of injection sites of local infiltration analgesia (LIA) in total knee arthroplasty (TKA).@*METHODS@#The relevant domestic and foreign literature in recent years was extensively reviewed. The neuroanatomy of the knee, and the research progress of the selection and the difference of effectiveness between different injection sites of LIA in clinical studies were summarized.@*RESULTS@#Large concentrations of nociceptors are present throughout the various tissues of the knee joint. Patellar tendon, subpatellar fat pad, lateral collateral ligament insertions, iliotibial band insertions, suprapatellar capsule, and posterior capsule were more sensitive to pain. Most current studies support injections into the lateral capsule, collateral ligament, retinaculum, quadriceps tendon, fat pad, and subcutaneous tissue. Whether to inject into the back of the knee and subperiosteum is controversial.@*CONCLUSION@#The relative difference of knee tissue sensitivity to pain has guiding significance for the selection of LIA injection site after TKA. Although researchers have conducted clinical trials on injection site and technique of LIA in TKA, there are certain limitations. The optimal scheme has not been determined yet, and further studies are needed.

Preparation and properties of a new artificial bone composite material / 中国修复重建外科杂志

OBJECTIVE@#To study the preparation and properties of the hyaluronic acid (HA)/α-calcium sulfate hemihydrate (α-CSH)/β-tricalcium phosphate (β-TCP) material (hereinafter referred to as composite material).@*METHODS@#Firstly, the α-CSH was prepared from calcium sulfate dihydrate by hydrothermal method, and the β-TCP was prepared by wet reaction of soluble calcium salt and phosphate. Secondly, the α-CSH and β-TCP were mixed in different proportions (10∶0, 9∶1, 8∶2, 7∶3, 5∶5, and 3∶7), and then mixed with HA solutions with concentrations of 0.1%, 0.25%, 0.5%, 1.0%, and 2.0%, respectively, at a liquid-solid ratio of 0.30 and 0.35 respectively to prepare HA/α-CSH/ β-TCP composite material. The α-CSH/β-TCP composite material prepared with α-CSH, β-TCP, and deionized water was used as the control. The composite material was analyzed by scanning electron microscope, X-ray diffraction analysis, initial/final setting time, degradation, compressive strength, dispersion, injectability, and cytotoxicity.@*RESULTS@#The HA/α-CSH/β-TCP composite material was prepared successfully. The composite material has rough surface, densely packed irregular block particles and strip particles, and microporous structures, with the pore size mainly between 5 and 15 μm. When the content of β-TCP increased, the initial/final setting time of composite material increased, the degradation rate decreased, and the compressive strength showed a trend of first increasing and then weakening; there were significant differences between the composite materials with different α-CSH/β-TCP proportion ( P<0.05). Adding HA improved the injectable property of the composite material, and it showed an increasing trend with the increase of concentration ( P<0.05), but it has no obvious effect on the setting time of composite material ( P>0.05). The cytotoxicity level of HA/α-CSH/β-TCP composite material ranged from 0 to 1, without cytotoxicity.@*CONCLUSION@#The HA/α-CSH/β-TCP composite materials have good biocompatibility. Theoretically, it can meet the clinical needs of bone defect repairing, and may be a new artificial bone material with potential clinical application prospect.

Analysis of characteristics of drug resistance gene mutation in HBV RT region of hepatitis B infected patients / 中华预防医学杂志

Objective: This article investigated the clinical characteristics and distribution of drug resistance mutation sites in HBV RT region of hepatitis B infected patients. Methods: Retrospective analysis was made on 1 948 patients with HBV infection, who had been tested for NAs resistance mutation and had a medical history of NAs in the Laboratory Department of the Fifth Medical Center of the PLA General Hospital from January 2020 to December 2021. Basic clinical information and drug resistance related mutation information were recorded. Meanwhile, the serological index data of hepatitis B were collected. Drug resistance gene mutant group and non-mutated group were grouped according to whether the drug resistance genes had a mutation in HBV RT region, and the clinical characteristics and genotype distribution of the two groups were statistically analyzed. The pattern of drug resistance gene mutation, number of mutation sites, drug resistance type and mutation of NAs resistance-related sites were analyzed in 917 patients with drug resistance gene mutation in HBV RT region. χ2 Inspection was used for counting data. Meanwhile, two independent samples t-test and Wilcoxon rank sum test were used for measurement data. Results: Among the 1 948 patients with chronic HBV infection, 917 patients had drug resistance gene mutation in RT region (47.07%). The proportion of patients with acute hepatitis B and CHB in HBV RT resistance gene mutant group was lower than that in the non-mutated group, while the proportion of patients with HBV-related cirrhosis was higher than that in the non-mutated group, these differences were statistically significant. Compared with the non-mutated group in HBV RT region, the age, the positive rates of HBeAg and HBV DNA, and HBV DNA load of these patients were increased in drug resistance gene mutant group, these differences were statistically significant. Genotypes of patients in both groups were dominated by C, followed by B and D. The proportion of patients with genotype C in HBV RT drug resistance gene mutant group was higher than that of non-mutated group, the difference was statistically significant. There were 53 gene mutation patterns in 917 patients with drug resistance gene mutation in HBV RT region, and the main pattern was rtL180M+rtM204V+rtS202G (9.70%). The mutation sites were dominated by 3 (20.74%). There were 5 types of drug resistance, LAM+Ldt (21.25%) was the most. Among the 18 sites that were clearly associated with LAM, ADV, ETV and Ldt resistance in the HBV RT region, 14 sites were mutated, and the most common mutation sites were rtL180M, rtM204V, rtM204 and rtS202G. what's more, the proportion of patients with NAs drug resistance was LAM>Ldt>ETV>ADV. Conclusion: In order to prevent adverse consequences of this study such as disease recurrence or disease progression caused by HBV drug resistance, HBV infected patients, who have long-term use of NAs antiviral therapy, should monitor the level of HBV DNA and drug resistance genes in HBV RT region in order to optimize the treatment plan in time or guide individualized treatment.

Trends and prediction of the burden of depression among adolescents aged 10 to 24 years in China from 1990 to 2019 / 中国学校卫生

Methods@#To analyze the trend of the burden of depression among adolescents aged 10-24 years from 1990 to 2019 and predict its future trend, so as to provide a theoretical basis for prevention and treatment.@*Methods@#The prevalence and disability adjusted life years (DALYs) were determined using the 2019 Global Burden of Disease Database. The joinpoint regression model was employed to analyze the changing trend of the burden of depression among adolescents aged 10-24 years in China from 1990 to 2019. The ARIMA time series model was established using R software to predict the development trend of depression among adolescents aged 10-24 years in China from 2020 to 2029.@*Results@#From 1990 to 2019, the prevalence and DALYs rate were higher among adolescents aged 10-24 years in comparison to the general population and males. Furthermore, the prevalence and DALYs rate were higher among adolescents aged 20-24 years than among those aged 15-19 and 10-14 years, with statistical significance ( P <0.05). The joinpoint regression analysis revealed that the prevalence of depression among adolescents aged 10-24 years showed an overall decreasing trend with an average annual rate of 1.61% ( t =-10.53, P <0.05), while the prevalence of depression among male and female adolescents in the same age group also showed a decreasing trend, with an average annual decreasing rate of 1.18% ( t =-5.79) and 1.79% ( t =-11.84) ( P <0.05), and the overall decline rate was greater among women than men. There was no significant change in the prevalence of depression among adolescents aged 10-14 years from 1990 to 2019 (AAPC=-0.28, P >0.05), while the prevalence of depression among adolescents aged 15-19 years and 20-24 years also showed a decreasing trend with an average annual rate of 1.43% ( t =-12.05) and 1.90% ( t =-24.92) ( P <0.05). The ARIMA model predicted that the prevalence of depression and the rate of DALYs among adolescents aged 10-24 years would continue to decline from 2020 to 2029.@*Conclusion@#The prevention and treatment of depression among adolescents aged 10-24 years in China should focus on females and those aged 20- 24 years old. We should start from the environment and micro-environment of adolescent growth and take active and effective measures to prevent the occurrence of adolescent depression.

Risk Factors Analysis and Prevention Strategy of Renke Space Edema Complicated with Vocal Cord Adhesion After CO2 Laser Resection / 中山大学学报(医学科学版)

ObjectiveTo investigate the prevention strategy of bilateral vocal cord adhesion after simultaneous Renke space edema resection under CO2 laser. MethodsSeventy patients who underwent CO2 laser resection of bilateral Renke space edema of vocal cords from June 2018 to June 2021 in our hospital were retrospectively selected for this study. According to their postoperative vocal cord adhesion， patients were divided into vocal cord adhesion group （35 cases） and silent band adhesion group （35 cases）， and the general data of the two groups were compared. Multivariate logistic regression analysis was used to evaluate the risk factors for postoperative vocal cord adhesion. The prediction model of postoperative morbidity risk of vocal cord adhesion was established by using chisquared automatic interaction detection （CHAID） classification tree algorithm， and the application value of the model was evaluated by benefit graph and index graph. ResultsMultivariate analysis showed that surgical range and depth of Ⅱ， laser power≥5 W and anterior connection involvement were the risk factors for postoperative vocal cord adhesion ［OR 95%CI： 6.113 （2.346， 17.451）； 5.214 （1.469， 15.263）； 18.651 （1.689， 36.203）］. The classification tree model showed that anterior articulation involvement was an important predictor of postoperative vocal cord adhesion （76.92%； χ2=11.993， P=0.001）， and the benefit graph and index graph showed good models. ConclusionClinical attention should be paid to surgical scope and depth， laser power and anterior union involvement， and timely prevention strategies should be formulated to reduce the risk of vocal cord adhesion in patients.

The modulation and mechanisms of high-altitude hypoxia in drug transport across the blood-brain barrier / 药学学报

The function of the central nervous system was significantly altered under high-altitude hypoxia, and these changes lead to central nervous system disease and affected the metabolism of drugs in vivo. The blood-brain barrier is essential for maintaining central nervous system stability and plays a key role in the regulation of drug metabolism, and barrier structure and dysfunction affect drug transport to the brain. Changes in the structure and function of the blood-brain barrier and the transport of drugs across the blood-brain barrier under high-altitude hypoxia are regulated by changes in brain microvascular endothelial cells, astrocytes and pericytes, and are regulated by drug metabolism factors such as drug transporters and drug metabolizing enzymes. This article reviews the effects of high-altitude hypoxia on the structure and function of the blood-brain barrier and the effects of changes in the blood-brain barrier on drug metabolism. We investigate the regulatory effects and underlying mechanisms of the blood-brain barrier and related pathways such as transcription factors, inflammatory factors and nuclear receptors on drug transport under high-altitude hypoxia.

Evaluation of inhibitory effect of tumor vaccine in colon carcinoma model mice / 中国生物制品学杂志

Objective@#To evaluate the inhibitory effect of tumor vaccines in colon carcinoma model mice.@*Methods@# Mouse bone marrow⁃derived dendritic cells（BMDCs）were stimulated by using CpG β⁃glucan nanoparticles（CNP）in vitro. The BMDCs were divided into PBS group，NP group（without CpG nanoparticles），Lysate group（MC38 cell lysate）and CpG group（CpG1826），which were determined for the expression of marker molecules on the surface by flow cytometry and for the contents of interleukin⁃6（IL⁃6）and IL⁃12p40 in the culture supernatant by ELISA. The tumor lysate nano⁃vaccine was pre⁃ pared by mixing 50 mg／mL tumor lysate（MC38 cell lysate）with 200 mg／mL CNP in a volume ratio of 1∶1，with which mice were subcutaneously immunized as Vaccine group. Vaccine group，PBS group，CNP group and Lysate group were im⁃ munized once a week，for three times in total. Mice were subcutaneously inoculated with MC38 cells，2 × 105 cells for each， in the right lower limb 1 h after the last immunization，and measured for tumor volume once every three days to plot the tumor growth curve. The ratios of CD3+ CD4+ T and CD3+ CD8+ T cells in the blood were analyzed by flow cytometry and the levels of tumor necrosis factor⁃α（TNF⁃α）and interferon γ（IFNγ）in the blood and spleen of mice were determined by ELISA.@*Results@# CNP effectively increased the expression of CD11c+ CD80+，CD11c+ CD86+，CD11c+ MHC⁃Ⅱ+ and the secretion of IL⁃6 and IL⁃12p40 in BMDCs in vitro，which were significantly higher than those in other 4 groups（t = 4. 3 ~ 46. 2，each P < 0. 05）. Compared with that of the other three groups，the tumor volume of mice in Vaccine group decreased significantly（t =2.6~3.4，eachP <0. 05）；TherewasnosignificantdifferenceinCD3+ CD8+ TandCD3+ CD8+ Tcellratios（t = 0.5~ 1. 9，each P > 0. 05）；The content of IFNγ in blood increased significantly（t = 3. 8 ~ 4. 6，P < 0. 05），while thatof TNF⁃α showed no significant difference（t = 0. 4 ~ 2. 0，each P > 0. 05）；However，the contents of IFN γ and TNF⁃α in spleen increased significantly（t = 6. 3 ~ 13. 0，each P < 0. 001）.@*Conclusion@#The prepared nano⁃vaccine of tumor lysate improvedtheimmune level in mice and effectively inhibited the growth of colon carcinoma.