Humulus lupulus L. extract and its active constituent xanthohumol attenuate oxidative stress and nerve injury induced by iron overload via activating AKT/GSK3ß and Nrf2/NQO1 pathways.

Hops, the dried female clusters from Humulus lupulus L., have traditionally been used as folk medicines for treating insomnia, neuralgia, and menopausal disorders. However, its pharmacological action on iron overload induced nerve damage has not been investigated. This study aims to evaluate the protective effects of hops extract (HLE) and its active constituent xanthohumol (XAN) on nerve injury induced by iron overload in vivo and in vitro, and to explore its underlying mechanism. The results showed that HLE and XAN significantly improved the memory impairment of iron overload mice, mainly manifested as shortened latency time, increased crossing platform times and spontaneous alternation ratio, and increased the expression of related proteins. Additionally, HLE and XAN significantly increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities, and remarkably decreased malondialdehyde (MDA) level in hippocampus. Also, HLE and XAN apparently reduced reactive oxygen species (ROS) content of PC12 cells induced by iron dextran (ID), and improved the oxidative stress level. Moreover, HLE and XAN significantly upregulated the expression of nuclear factor E2-related factor (Nrf2), NAD(P)H quinone oxidoreductase (NQO1), heme oxygenase-1 (HO-1), SOD, phosphorylated AKT (p-AKT), and phosphorylated GSK3ß (p-GSK3ß) both in hippocampus and PC12 cells. These findings demonstrated the protective effect of HLE and XAN against iron-induced memory impairment, which is attributed to its antioxidant profile by activation of AKT/GSK3ß and Nrf2/NQO1 pathways. Also, it was suggested that hops could be a potential candidate for iron overload-related neurological diseases treatment.

Nervous tract-bioinspired multi-nanoyarn model system regulating neural differentiation and its transcriptional architecture at single-cell resolution.

Bioinspired by native nervous tracts, a spinal cord-mimicking model system that was composed of multiple nanofibrous yarns (NYs) ensheathed in a nanofibrous tube was constructed by an innovative electrospinning-based fabrication and integration strategy. The infilling NYs exhibited uniaxially aligned nanofibrous architecture that had a great resemblance to spatially-arranged native nervous tracts, while the outer nanofibrous tubes functioned as an artificial dura matter to provide a stable intraluminal microenvironment. The three-dimensional (3D) NYs were demonstrated to induce alignment, facilitate migration, promote neuronal differentiation, and even phenotypic maturation of seeded neural stem and progenitor cells (NSPCs), while inhibiting gliogenesis. Single-cell transcriptome analysis showed that the NSPC-loaded 3D NY model shared many similarities with native spinal cords, with a great increase in excitatory/inhibitory (EI) neuron ratio. Curcumin, as a model drug, was encapsulated into nanofibers of NYs to exert an antioxidant effect and enhanced axon regeneration. Overall, this study provides a new paradigm for the development of a next-generation in vitro neuronal model system via anatomically accurate nervous tract simulation and constructs a blueprint for the research on NSPC diversification in the biomimetic microenvironment.

Evaluating the efficacy and safety of transcranial pulse stimulation on adolescents with attention deficit hyperactivity disorder: Study protocol of a pilot randomized, double-blind, sham-controlled trial.

Background: Traditional treatment alone might not effectively control the severity of attention deficit hyperactivity disorder (ADHD) symptoms. Transcranial pulse stimulation (TPS) is a non-invasive brain stimulation (NIBS) technology used on older adults with mild neurocognitive disorders and adults with major depressive disorder. However, there has been no study conducted on young adolescents with ADHD. This will be the first nationwide study evaluating the efficacy and safety of TPS in the treatment of ADHD among young adolescents in Hong Kong. Methods: This study proposes a double-blinded, randomized, sham-controlled trial including TPS as an intervention group and a sham TPS group. Both groups will be measured at baseline (T1), immediately after the intervention (T2), and at the 1-month (T3) and 3-month follow-ups (T4). Recruitment: A total of 30 subjects aged between 12 and 17 years, diagnosed with attention deficit hyperactivity disorder (ADHD), will be recruited in this study. All subjects will be computer randomized into either the intervention group or the sham TPS group on a 1:1 ratio. Intervention: All subjects in each group will have to undertake functional MRI (fMRI) before and after six 30-min TPS sessions, which will be completed in 2 weeks' time. Outcomes: Baseline measurements and post-TPS evaluation of the ADHD symptoms and executive functions will also be conducted on all participants. The 1- and 3-month follow-up periods will be used to assess the long-term sustainability of the TPS intervention. For statistical analysis, ANOVA with repeated measures will be used to analyze data. Missing data were managed by multiple imputations. The level of significance will be set to p < 0.05. Significance of the study: Results emerging from this study will generate new knowledge to ascertain whether TPS can be used as a top-on treatment for ADHD. Clinical trial registration: clinicaltrails.gov, identifier: NCT05422274.

Morchella esculenta mushroom polysaccharide attenuates diabetes and modulates intestinal permeability and gut microbiota in a type 2 diabetic mice model.

Type 2 diabetes mellitus (T2DM) is a health issue that causes serious worldwide economic problems. It has previously been reported that natural polysaccharides have been studied with regard to regulating the gut microbiota, which plays an important role in T2DM. Here, we investigate the effects of Morchella esculenta polysaccharide (MEP) on a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM in BALB/c mice. The administration of MEP effectively regulated hyperglycemia and hyperlipidemia and improved insulin sensitivity. We also determined an improvement in gut microbiota composition by 16sRNA pyrosequencing. Treatment with MEP showed an increase in beneficial bacteria, i.e., Lactobacillus and Firmicutes, while the proportion of the opportunistic bacteria Actinobacteria, Corynebacterium, and Facklamia decreased. Furthermore, the treatment of T2DM mice with MEP resulted in reduced endotoxemia and insulin resistance-related pro-inflammatory cytokines interleukin 1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). Moreover, MEP treatment improved intestinal permeability by modulating the expression of the colon tight-junction proteins zonula occludens-1 (ZO-1), occludin, claudin-1, and mucin-2 protein (MUC2). Additionally, MEP administration affects the metagenome of microbial communities in T2DM mice by altering the functional metabolic pathways. All these findings suggested that MEP is a beneficial prebiotic associated with ameliorating the gut microbiota and its metabolites in T2DM.

Characterization of SOD and GPX Gene Families in the Soybeans in Response to Drought and Salinity Stresses.

Plant stresses causing accumulation of reactive oxidative species (ROS) are scavenged by effective antioxidant defense systems. Therefore, the present study performed genome-wide identification of superoxide dismutase (SOD) and glutathione peroxidase (GPX) gene families in cultivated and wild soybeans, and 11 other legume species. We identified a total of 101 and 95 genes of SOD and GPX, respectively, across thirteen legume species. The highest numbers of SODs and GPXs were identified in cultivated (Glycine max) and wild (Glycine soja). A comparative phylogenetic study revealed highest homology among the SODs and GPXs of cultivated and wild soybeans relative to other legumes. The exon/intron structure, motif and synteny blocks were conserved in both soybean species. According to Ka/Ks, purifying the selection played the major evolutionary role in these gene families, and segmental duplication are major driving force for SODs and GPXs expansion. In addition, the qRT-PCR analysis of the G. max and G. soja SOD and GPX genes revealed significant differential expression of these genes in response to oxidative, drought and salinity stresses in root tissue. In conclusion, our study provides new insights for the evolution of SOD and GPX gene families in legumes, and provides resources for further functional characterization of these genes for multiple stresses.

The influence of the cross-modal emotional pre-preparation effect on audiovisual integration.

Previous studies have shown that the cross-modal pre-preparation effect is an important factor for audiovisual integration. However, the facilitating influence of the pre-preparation effect on the integration of emotional cues remains unclear. Therefore, this study examined the emotional pre-preparation effect during the multistage process of audiovisual integration. Event-related potentials (ERPs) were recorded while participants performed a synchronous or asynchronous integration task with fearful or neutral stimuli. The results indicated that, compared with the sum of the unisensory presentation of visual (V) and auditory (A) stimuli (A+V), only fearful audiovisual stimuli induced a decreased N1 and an enhanced P2; this was not found for the neutral stimuli. Moreover, the fearful stimuli triggered a larger P2 than the neutral stimuli in the audiovisual condition, but not in the sum of the combined (A+V) waveforms. Our findings imply that, in the early perceptual processing stage and perceptual fine processing stage, fear improves the processing efficiency of the emotional audiovisual integration. In the last cognitively assessing stage, the fearful audiovisual induced a larger late positive component (LPC) than the neutral audiovisual. Moreover, the asynchronous-audiovisual induced a greater LPC than the synchronous-audiovisual during the 400-550 ms period. The different integration effects between the fearful and neutral stimuli may reflect the existence of distinct mechanisms of the pre-preparation in terms of the emotional dimension. In light of these results, we present a cross-modal emotional pre-preparation effect involving a three-phase emotional audiovisual integration.

Effects of Busheng Huayu Qianggu prescription in elderly patients with osteoporotic lumbar fracture of kidney deficiency and blood stasis type / 实用医学杂志

Objective To investigate the application value of Bushen Huayu Qianggu prescription in the treatment of senile osteoporotic lumbar fracture with kidney deficiency and blood stasis type.Methods All elderly patients with osteoporotic lumbar fractures of kidney deficiency and blood stasis were treated in our hospital from September 2021 to March 2023 and randomly divided into 68 cases in both groups.The control group was treated with conventional Western medicine,and the observation group was treated with BushengHuayuQiang Gu prescrip-tion for 12 weeks.Results Serum D-dimer(D-D),interleukin-6(IL-6)and prostaglandin E2(PGE2)were lower in the observation group than in the control group,and vascular endothelial growth factor(VEGF)and β-endorphin(β-EP)were higher(P<0.05);serum osteoprotegerin(OPG)and bone morphogenetic protein-2(BMP-2)were higher in the observation group(P<0.05);total effective rate was as high as 95.59%(65%)(P<0.05);bone mineral density(BMD)was higher in the observation group than in the control group after treatment,and the total symptom score and Cobb angle of Chinese medicine were lower(P<0.05);the total effective rate of the observation group was as high as 95.59%(65/68),higher than that of the control groupwhich was 80.88%(55/68)(P<0.05).Conclusion Combined treatment with BushenHuayuQianggu prescription can reduce inflammation,regulate bone metabolism,promote bone mineral density and improve clinical efficacy for senily-aged lumbar osteoporotic frac-ture caused by kidney deficiency and blood stasis.

Relationship between dry eye disease and physical and mental health in primary and secondary school teachers / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To evaluate the relationship between dry eye disease(DED)and physical and mental health in teachers, and to explore its mechanism and propose intervention measures.METHODS:Cross-sectional study. A total of 183 teachers from three primary and secondary schools in the urban area of Linyi City, Shandong Province were enrolled in the study. DED symptoms were quantified using the ocular surface disease index(OSDI)questionnaire. A compact version of the depression, anxiety, and stress scale(DASS-21)was used to evaluate psychological state. The relationship between potential influencing factors and DED was evaluated by independent sample t-test of quantitative variables and χ2test of classified variables. Logistic regression analysis was used for multivariate analysis to determine the influencing factors of DED. Pearson correlation coefficient was used to analyze the correlation between OSDI score and depression, anxiety and stress.RESULTS: There were 183 teachers, including 44 males(24.0%)and 139 females(76.0%), aged from 22 to 57 years, with an average age of(34.2±8.6)years. The prevalence of DED was 60.0%(109/183; 95%CI 52.4%-66.7%). The prevalence of depression was 26.2%(48/183; 95%CI 19.8%-32.7%); anxiety prevalence was 39.3%(72/183; 95%CI 32.2%-46.5%); and stress prevalence was 23.0%(42/183; 95%CI 16.8%-29.1%). The univariate analysis showed that increased age, increased working years, increased visual display terminal(VDT)application time, longer written working hours, reduced sleep hours, less alcohol consumption, and high scores of depression, anxiety and stress were all factors affecting DED(all P&#x0026;#x003C;0.05). Using depression scores as the psychological index, multivariate Logistic regression analysis showed that years of work, VDT application time, written working hours, sleep time, alcohol consumption and depression score were the influencing factors of DED(all P&#x0026;#x003C;0.05); Using anxiety scores as the psychological index, multivariate Logistic regression analysis showed that years of work, VDT application time, written working hours and stress scores were the influencing factors of DED(all P&#x0026;#x003C;0.05); Using stress scores as the psychological index, multivariate Logistic regression analysis showed that years of work, VDT application time, written working hours and stress scores were the influencing factors of DED(all P&#x0026;#x003C;0.05). OSDI scores were positively correlated with depression, anxiety, and stress scores in the DED group(P&#x0026;#x003C;0.05)and across all participants(P&#x0026;#x003C;0.05). In the severe DED group, OSDI scores were positively related to depression, anxiety, and stress scores(P&#x0026;#x003C;0.05).CONCLUSION: The prevalence of DED is high among the teachers. Alcohol consumption, reduced sleep, longer working years, longer VDT usage and longer written working hours are the influencing factors of DED. In severe DED group, DED is highly correlated with depression, anxiety, and stress. We should pay attention to teachers' DED and related physical and mental health problems, and actively prevent and make early diagnosis and treatment.

Risk analysis of re⁃fracture after percutaneous kyphoplasty in elderly patients with osteoporotic thoracolumbar compression fractures and construction of a columnar graph prediction model / 解剖学报

Objective To investigate the risk factors for re-fracture after percutaneous kyphoplasty (PKP) in elderly patients with osteoporotic thoracolumbar compression fractures and to construct a line graph prediction model. Methods One hundred and eighty-two elderly patients with osteoporotic thoracolumbar compression fractures treated with PKP from January 2016 to November 2019 were selected for the study‚ and the patients were continuously followed up for 3 years after surgery. Clinical data were collected from both groups; Receiver operating characteristic (ROC) curve analysis was performed on the measures; Logistic regression analysis was performed to determine the independent risk factors affecting postoperative re-fracture in PKP; the R language software 4. 0 “rms” package was used to construct a predictive model for the line graph‚ and the calibration and decision curves were used to internally validate the predictive model for the line graph and for clinical evaluation of predictive performance. Results The differences between the two groups were statistically significant (P0. 22‚ which could provide a net clinical benefit‚ and the net clinical benefit was higher than the independent predictors. Conclusion BMD‚ number of injured vertebrae‚ single-segment cement injection‚ cement leakage‚ pre-and post-PKP vertebral height difference‚ and posterior convexity angle change are independent risk factors affecting the recurrent fracture after PKP in elderly patients with osteoporotic thoracolumbar compression fracture‚ and this study constructs a column line graph model to predict the recurrent fracture after PKP in elderly patients with osteoporotic thoracolumbar compression fracture as a predictor for clinical. This study provides an important reference for clinical prevention and treatment‚ and has clinical application value.

Testosterone Replacement Therapy Has Limited Effect on Increasing Bone Mass Density in Older Men: a Meta-analysis.

BACKGROUND: Testosterone insufficiency may play a role in age-related decreases in bone mass density (BMD) and osteoporosis in aging men. Testosterone replacement therapy (T therapy) seems to be a simple and convenient way to increase BMD and improve the condition of osteoporosis. OBJECTIVE: To evaluate the effects of T therapy in increasing BMD among older men with low serum testosterone concentrations. METHODS: A comprehensive search in the PubMed, EMBASE, Web of Science and Cochrane Central databases was undertaken for randomized controlled trials (RCTs) on the effect of T therapy on osteoporosis in aging men. Primary outcome measures were the change in BMD, bone turnover markers, prostate symptoms, body composition, metabolic and endocrine system markers. The final search was performed in October 2018. RESULTS: Seven RCTs were included. A total of 800 patients met the inclusion criteria. T therapy did not significantly reverse the trend toward decreasing BMD in the spine, femoral neck, Ward's triangle and the whole body, with the exception of the trochanter and total hip. In addition, T therapy increased prostate size, lean mass, sex hormone levels; reduced HDL concentration; and had no statistical effect on prostate symptoms, body composition, serum hormones and metabolism. CONCLUSION: T therapy is not effective in increasing BMD in older men. In addition, it has limited effects on prostate-specific antigen (PSA), the International Prostate Symptom Score (IPSS), body mass index (BMI), fat mass, parathyroid hormone (PTH), 25-VitD and lipid metabolism, although it can increase prostate size, lean mass, and sex hormone levels, and reduce glucose levels and HDL concentrations.

Study on the Structural Changes and Influencing Factors of Hospitalization Expenses of Diabetic Patients / 中国卫生经济

Objective:By analyzing the cost change trend,internal structure change and main influencing factors of diabetes inpatients'hospitalization expenses,it provides empirical basis for promoting the reform of medical service prices,optimizing the internal structure of hospitalization expenses,effectively controlling hospitalization expenses,and reducing the economic burden of diabetes inpatients.Methods:Using the first page data of medical records of 13 426 diabetes inpatients in the target hospital from 2017 to 2021,it analyzes the structural change of diabetes inpatients'hospitalization expenses by using structural change degree and grey correlation degree methods,and analyzes the influencing factors of hospitalization expenses by using linear regression and BP neural network model.Results:Drug expenses and medical technology expenses are the top two in the proportion of total hospitalization expenses of discharged patients with diabetes,and they account for a large proportion in the total hospitalization expenses.The results of structural change and grey correlation show that drug expenses and medical technology expenses are these two factors that cause changes in the total hospitalization cost structure and have a high correlation with the total hospitalization cost,with a cumulative contribution rate of 90.50％.According to the results of linear regression and neural network model,the length of stay is the most important factor affecting the total cost of hospitalization of diabetes patients,followed by the number of operations/procedures and diagnoses.Conclusion:The internal composition of hospitalization expenses for diabetes patients is unreasonable.The proportion of drug expenses and medical technology expenses is too high.The proportion of medical and nursing expenses reflecting the technical labor value of medical personnel is relatively low.The structure of medical income needs to be further optimized.The length of stay is the most critical factor affecting the hospitalization expenses of diabetes patients.Reasonable control of the length of stay can effectively control the unreasonable growth of medical expenses and reduce the economic burden of diabetes patients.

Differences in exosome miRNAs in human breast milk between preterm and full-term infants / 中国儿童保健杂志

【Objective】 To evaluate the differential miRNA expression of breast milk exosome in premature and full-term groups, and to analyze the regulatory pathways by bioinformatics, so as to provide guidance and scientific basis for the growth and development of premature infants and the prevention and treatment of related diseases. 【Methods】 From August 2020 to June 2021, breast milk samples from 13 premature (premate group) and 9 full-term infants(full-term group) in the Department of Child Health Care of the Second Affiliated Hospital of Nanjing Medical University were collected to extract exosomes. The miRNAs of two groups of breast milk exosomes were sequenced by high-throughput sequencing. According to the sequencing results, miRNA expression profiles of milk exosome were analyzed. Biological function software was used to carry out GO and KEGG pathway analysis of differential miRNA. 【Results】 The expression of miRNA in human milk exosomes was rich, especially hsa-miR-148a-3p,hsa-let-7b-5p, hsa-let-7g-5p, hsa-miR-22-3p, hsa-miR-99a-5p, hsa-miR-200, hsa-miR-146b-5p and hsa-miR-26a-5p were relatively high expressed in preterm group and full-term group. Differential expression analysis showed that compared with full-term infant breast milk, 7 miRNAs were up-regulated(log2|fold change|=2.803, 2.714, 1.632, 2.360, 1.350, 3.387, 2.137, respectively), and 5 miRNAs were down-regulated(log2|fold change|=-2.553, -2.197, -2.771, -1.395, -1.136, respectively)(|fold change>2|, P<0.05) in breast milk for preterm infants. In these differential expressed miRNAs, down-regulated miR-29b(P=0.001) and up-regulated miR-133a-3p(P=0.004) were associated with inflammation, and up-regulated miR-126-5p(P=0.021) and miR-126-3p(P=0.041) were associated with lipid metabolism. The fatty acid biosynthesis pathway was obviously enriched in preterm group. MiR-7-5p, miR-29b-3p and miR-100-5p played a role in the fatty acid synthesis pathway. 【Conclusions】 Exosomal miRNAs are rich in breast milk, and have significant differences between preterm and full-term infants′ mothers. The differentially expressed miRNA in preterm infants treast milk may be related to inflammation and promote the growth and development of preterm infants through the fatty acid biosynthesis pathway.

Phenotypic evaluation of Ttc37 knockout mouse as type Ⅰ tricho-hepato-enteric syndrome model / 复旦学报（医学版）

Objective To establish a mouse model of type Ⅰ tricho-hepato-enteric syndrome(THES)induced by Ttc37 deficiency.Methods Ttc37 flox strain was established by site-specifically inserted loxP sites into Ttc37 gene via CRISPR/CAS9 technology.Ubiquitously expressed CAG-Cre was introduced for all-tissue removal of Ttc37 in Ttc37flox/flox;CAG-Cre mice.The knock-out effect was confirmed by fluorescence quantitative PCR and Western blot.Phenotypic evaluations were conducted in 8-week-old mice including hematoxylin-eosin staining of skin,spleen,liver,bladder,and gastrointestinal tract(GI),serum enzyme activity assay of aspartate aminotransferase(AST)and alanine aminotransferase(ALT),measurement of serum hemoglobin level,and ELISA for IgG and IgM level upon antigen immunization.Results Similar to type Ⅰ THES patients,Ttc37flox/flox;CAG-Cre mice exhibited impaired development of hair shaft,epidermis,B cell and eyes,while liver,GI,bladder and serum hemoglobin level seemed normal under unstressed condition.Conclusion A novel mouse model of typeⅠ THES was constructed successfully,which was applicable for pathological study.

The association between metformin therapy and risk of gynecological cancer in patients: Two meta-analyses.

BACKGROUND: Recently, metformin, first-line drug for type 2 diabetes, has been reported to treat some gynecological tumors. However, these epidemiological studies have never been formally summarized. Considering a single study may lack the power to provide reliable conclusion, we performed two meta-analyses with different indicators to assess metformin's role in reducing the risk of gynecological cancers. MATERIALS AND METHODS: A systematic literature search was carried out in PubMed, Medline (Ovid), Embase database (last search was performed on August 15, 2018). The relative risk (RR) along with a random-effects model were performed on Revman 5.3 and STATA 15.1 for risks analyzing. RESULTS: A total of 1,710,080 patients in 7 studies were included in first meta-analysis. The results suggested metformin may reduce the risk of gynecological cancers (RR=0.49, 95%CI=0.29-0.82, and p=0.006). In the subgroup analyses: significantly decreased risks were found among Asians (RR=0.27, 95%CI=0.17-0.41, and p<0.00001), ovarian cancer (RR=0.18, 95%CI=0.12-0.28, and p<0.00001), and cervical cancer (RR=0.60, 95%CI=0.43-0.83, and p=0.002), but not in Caucasians (RR=0.81, 95%CI=0.50-1.32, and p=0.40) or in endometrial cancer (RR=0.71, 95%CI=0.29-1.74, and p=0.45). Meanwhile, another total of 8,335,332 cumulative follow-up years, person years, were conducted in 8 studies. The results indicated no statistical significance in general (RR=0.59, 95%CI=0.32-1.10, p=0.10), and no difference in Caucasians (RR=1.15, 95%CI=0.88-1.48, and p=0.30), endometrial cancer (RR=0.89, 95%CI=0.27-2.95, and p=0.84) or ovarian cancer (RR=0.37, 95%CI=0.09-1.49, and p=0.16) when performing subgroup analyses. However, in the subgroup analyses, results in Asians (RR=0.26, 95%CI=0.17-0.40, and p<0.00001) and cervical cancer (RR=0.56, 95%CI=0.40-0.78, and p=0.0005) had an apparent significance. CONCLUSIONS: The results suggested the metformin can be used as a potential anticarcinogenic drug for gynecological cancers' prevention, especially for Asians and cervical cancer. The question remains, still, whether metformin is beneficial for ovarian cancer. Also, we don't know whether it is worth to give metformin to non-diabetes to prevent gynecological cancer.

Erythropoietin-overexpressed umbilical cord mesenchymal stem cells inhibit neuroapoptosis in ischemic-hypoxic SH-SY5Y and its mechanism / 中国组织工程研究

BACKGROUND:Previous studies have successfully constructed erythropoietin-overexpressed umbilical cord mesenchymal stem cells.It was found that the apoptosis of ischemic and hypoxic human neuroblastoma cell line(SH-SY5Y)was significantly reduced by erythropoietin-overexpressed umbilical cord mesenchymal stem cells. OBJECTIVE:To explore the possible neuroprotective mechanisms of erythropoietin-overexpressed umbilical cord mesenchymal stem cells against ischemic-hypoxic SH-SY5Y and their associated epigenetic mechanisms. METHODS:Oxygen-glucose deprivation was applied to ischemia-hypoxia-induced SH-SY5Y cell injury,and multifactorial assays were applied to detect the expression levels of inflammatory factors in the cells before and after hypoxia and co-culture,respectively,with mesenchymal stem cells,as well as lentiviral-transfected null-loaded plasmids of the negative control mesenchymal stem cells and erythropoietin-overexpressed umbilical cord mesenchymal stem cells.The expression levels of supernatant inflammatory factors were detected by multifactor assay after co-culture.Proteomics was used to detect the differentially expressed proteins of negative control mesenchymal stem cells and erythropoietin-overexpressed umbilical cord mesenchymal stem cells.Cleavage under targets and tagmentation sequencing was applied to detect genomic H3K4me2 modification,and joint analysis was conducted with RNA-sequencing.Lentiviral vector infection was applied to construct the stable knockdown of REST in SH-SY5Y cells.qRT-PCR and western blot assay were performed to detect the expression level of REST.The apoptosis was detected by flow cytometry after co-culture of oxygen-glucose deprivation treatment with erythropoietin-overexpressed umbilical cord mesenchymal stem cells.The expression difference of H3K36me3 group proteins was detected by western blot assay,and transcriptome sequencing was performed to analyze the differentially expressed genes. RESULTS AND CONCLUSION:(1)Compared with the control group,monocyte chemotactic protein 1,interleukin-6,interleukin-18,and interleukin-1 beta,interferon α2,and interleukin-23 levels significantly increased in the cerebrospinal fluid supernatant of patients with ischemic-hypoxic encephalopathy(P<0.01).(2)After co-culturing SH-SY5Y cells with erythropoietin-overexpressed umbilical cord mesenchymal stem cells under ischemia and hypoxia,the expression levels of monocyte chemotactic protein 1 and interleukin-6 were significantly reduced.(3)Analysis of protein network interactions revealed significant downregulation of monocyte chemotactic protein 1,interleukin-6 related regulatory proteins CXCL1 and BGN.(4)Transcriptome sequencing analysis found that pro-inflammatory genes were down-regulated,and functional enrichment of histone modifications,and the expression of transcription factors REST and TET3 significantly up-regulated in the erythropoietin-overexpressed umbilical cord mesenchymal stem cell group compared with the negative control mesenchymal stem cell group.(5)Combined analysis of transcriptome sequencing and cleavage under targets and tagmentation revealed changes in epigenetic levels as well as significant activation of the promoter regions of transcription factors REST and TET3.(6)Stable knockdown REST in SH-SY5Y cells was successfully constructed;the transcript levels of REST mRNA and protein expression were both decreased.(7)After the REST knockdown SH-SY5Y cells were co-cultured with erythropoietin-overexpressed umbilical cord mesenchymal stem cells,apoptosis was significantly increased and H3K36me3 expression was significantly decreased.Transcriptome sequencing results showed that the expression of inflammation-related genes Aldh1l2 and Cth,as well as apoptosis-suppressor genes Mapk8ip1 and Sod2 was reduced at mRNA transcription level(P<0.01).(8)It is concluded that erythropoietin-overexpressed umbilical cord mesenchymal stem cells activated the expression of REST and TET3 by altering the kurtosis of H3K4me2 and upregulated the modification level of H3K36me3,which in turn regulated the expression of inflammation-related genes Aldh1l2 and Cth,as well as apoptosis-suppressor genes Mapk8ip1 and Sod2,and facilitated neuronal survival.

The experimental study of X-ray diagnosis of closed reduction rotational displacement of femoral neck fractures / 中华骨科杂志

Objective:To explore the optimal index of rotational displacement of femoral neck fractures by modeling the axial rotational displacement of femoral neck fractures after reduction and based on X-ray projections.Methods:Six dry human femur specimens, comprising 2 males and 4 females, were utilized in the study. Design and manufacture a proximal femur ortholateral and oblique X-ray casting jigs and mounts. The femoral neck fracture was modeled on the femoral specimen, with Pauwells 30°, 50°, and 70° models (2 each) made according to Pauwells typing. The fractures were manually repositioned with residual anterior 20°, 40° and 60° axial rotational displacements. Each fracture model was projected at different angles (pedicled 40°, pedicled 20°, vertical 0°, cephalad 20°, and cephalad 40°), and the trabecular angle and Garden's alignment index of the model were measured to observe the imaging characteristics of the fracture line on the medial oblique and lateral oblique radiographs.Results:In the presence of a 20° and 40° anterior rotational displacement following reduction of a femoral neck fracture, the trabecular angle in the rotationally displaced group was not significantly different from that of the anatomically repositioned group in various projection positions. However, when a residual rotational displacement of 60° was present, the trabeculae appeared blurred at most projection angles in the Pauwells 30° and 50° models, failing to measure trabecular angles. In the Pauwells 70° fracture model, the trabecular angle in the rotational displacement group was significantly different from that in the anatomical reduction group. In anteroposterior radiographs, when the anterior rotation displacement was 60° in the Pauwells 70° group, Garden's contralateral index showed an unsatisfactory restoration (150°, 142°), whereas all rotationally displaced models in the Pauwells 30° and Pauwells 50° groups had a Garden's contralateral index of >155°, which achieved an acceptable restoration. In lateral radiographs, all rotational displacement models with Garden's alignment index>180° failed to achieve acceptable repositioning, and the larger the Pauwells angle the greater the Garden's alignment index at the same rotational displacement. In the internal oblique position with a bias towards the foot side, the image showed partial overlap between the femoral head and the shaft, making it difficult to assess the quality of the reduction. Conversely, when projected cephalad, the femoral neck appeared longer, particularly at a projection angle of 40° cephalad, allowing for clear observation of the fracture line and the anatomy of the proximal femur. The trabeculae were not well visualized in the external oblique position.Conclusion:There are limitations in applying the trabecular angle to assess the axial rotational displacement of the femoral head after reduction of femoral neck fractures. The Pauwells 70° with residual rotational anterior displacement of 60° was the only way to detect axial rotational displacement of the femoral head on anteroposterior radiographs Garden's alignment index. For the determination of axial rotational displacement of the femoral head, the Garden's alignment index on lateral radiographs provides higher reliability.

Research progress on mechanisms of mutual regulation between the muscular system and the skeletal system in the elderly / 中华老年医学杂志

Examining mechanisms involved in the mutual regulation between the muscular system and the skeletal system, elucidating the key issues responsible for loss of muscle and bone mass and strength, and thus halting the progression of these conditions are critical measures for reducing fractures caused by falls and subsequent disability and mortality.At present, most studies have treated the muscular system and the skeletal system separately, often ignoring the mutual regulation and connections between them.This article reviews the current research progress on the mechanisms of interaction between the two systems, aiming to provide a basis for the prevention, diagnosis and treatment of disuse-related diseases in the elderly population.

A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.

Clinical study of intra-articular injection of autologous PRP combined with Tongbi San fumigation in the treatment of early knee osteoarthritis / 国际中医中药杂志

Objective:To evaluate the efficacy of intra-articular injection of autologous platelet-rich plasma (PRP) combined with Tongbi Powder fumigation in the treatment of early knee osteoarthritis (KOA).Methods:Randomized controlled trial. Totally 160 patients with KOA in Tai'an Second Hospital of Traditional Chinese Medicine were enrolled between March 2021 and March 2022. According to random number table method, they were divided into two groups, with 80 cases in each group. The control group was given routine treatment, while observation group was given intra-articular injection of autologous PRP combined with Tongbi Powder fumigation. All were treated for 3 weeks. The knee function was evaluated by Western Ontario and McMaster University (WOMAC) osteoarthritis index. The activities of daily living were evaluated by Lysholm knee scale (LKS). The pain degree was evaluated by VAS. The levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected by ELISA. The adverse reactions during treatment were observed and recorded. The clinical efficacy was evaluated.Results:The total effective rate of the observation group was 95.0% (76/80), and that of the control group was 77.5% (62/80), with statistical significance ( χ2=10.33, P<0.01). At 1, 3 and 6 months after treatment, the WOMAC score of the observation group was lower than that of the control group ( F=15.63, P<0.01), the LKS score was higher than that of the control group ( F=55.23, P<0.01), and the VAS score was lower than that of the control group ( F=11.93, P<0.01). After treatment, the observation group IL-1β [(51.75±2.74)μg/L vs. (63.38±3.31) μg/L, t=24.21], TNF- α [(10.58±1.25) μg/L vs. (11.62±1.84) μg/L, t=4.18] were lower than those in the control group ( P<0.01). The incidence of adverse reactions was 10.0% (8/80) in the observation group and 7.5% (6/80) in the control group, without statistical significance ( χ2=0.31, P=0.576). Conclusion:Intra-articular injection of autologous PRP combined with Tongbi San fumigation can effectively improve knee function and activities of living ability, relieve pain symptoms, reduce inflammatory response and improve clinical curative effect in early KOA.

Optimization of extraction technology for Puji disinfection oral liquid based on combination of G1-entropy weight method and Box-Behnken design-response surface methodology / 中国药师

Objective To optimize the extraction process of Puji disinfection oral liquid.Methods Based on Box-Behnken design,the extraction process of volatile oil was optimized with the extraction rate of volatile oil as index.Based on Box-Behnken design combined with G1-entropy weight method,the extraction rate and dry extract rate of(R,S)-epigoitrin,hesperidin,baicalin,berberine hydrochloride and arctiin were used as indices to optimize the water extraction process.Results The optimum extraction conditions of volatile oil from Puji disinfection oral liquid were as follows:adding 10 times of water,soaking time of 1.5 h and extraction time of 5 h.The optimal water extraction process was as follows:10 times of water,1.8 h of extraction time and 2 times of extraction.Under the optimal extraction conditions,there was no significant difference among the three batches of verification tests.Conclusion The optimized extraction process is stable and feasible,which can provide the basis for the subsequent experimental study and industrial production of Puji disinfection oral liquid.