Low-temperature condensation deposition method for 3D printing of bone tissue engineering poly-L-lactic acid/pearl powder composite scaffold / 中国组织工程研究

BACKGROUND:The repair of large-scale bone defects is still facing serious challenges.It is of great significance to develop personalized,low-cost,and osteogenic-inducing tissue engineering scaffolds for bone repair. OBJECTIVE:To explore the process of 3D printing bone tissue engineering scaffold containing pearl composite material by low-temperature condensation deposition method,and further test the physicochemical properties and in vitro biological functions of the composite scaffold. METHODS:Pearl powder was prepared by grinding and sieving.The pearl powder of different qualities was added into the poly-L-lactic acid ink,so that the mass ratio of pearl powder to poly-L-lactic acid was 0,0.1,0.2,0.3,and 0.5,respectively.The 3D-printed poly-L-lactic acid/pearl powder scaffolds were prepared using the low-temperature condensation deposition method.The microstructure,compressive properties,water contact angle,cytocompatibility,and in vitro bone differentiation ability of the printed poly-L-lactic acid/pearl powder composite scaffolds were detected. RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the five groups of scaffolds all had micropores with a diameter of 2 μm or even smaller,irregular shapes and interconnectivity.(2)All the five groups had good compressive properties.The compressive strength of the pearl powder 0.5 group was higher than that of the other four groups(P<0.05).The water contact angle of the pearl powder 0.2 group and the pearl powder 0.5 group was smaller than that of the pearl powder 0 group(P<0.01,P<0.001).(3)Bone marrow mesenchymal stem cells were co-cultured with five groups of scaffolds for 1,3,and 5 days,respectively.The cell proliferation in pearl powder 0.1,0.2,0.3,and 0.5 groups cultured for 3 and 5 days was faster than that in pearl powder 0 group(P<0.05).After 1 day of culture,live-dead staining exhibited that the number of cells on the scaffold was small,but all of them were living cells.(4)Bone marrow mesenchymal stem cells were inoculated on the scaffold surface of the pearl powder 0 group and pearl powder 0.1 group respectively for osteogenic differentiation.The alkaline phosphatase activity induced for 4 and 6 days in the pearl powder 0.1 group was higher than that in the pearl powder 0 group(P<0.05).(5)The results showed that the poly-L-lactic acid/pearl powder composite scaffold had good compressive strength,hydrophilicity,cytocompatibility,and osteogenic properties.

Efficacy of melatonin therapy for neonatal hypoxic-ischemic encephalopathy: systematic review and meta-analysis / 中国新生儿科杂志

Objective:To systematically evaluate the clinical efficacy of melatonin for neonatal hypoxic-ischemic encephalopathy (HIE).Methods:From the inception of the databases to December 1, 2022, randomized controlled trials (RCTs) and cohort studies on the use of melatonin for HIE were searched in the following databases: PubMed, Web of Science, Cochrane library, Embase, Chinese Medical Journal Full-text Database, CNKI, Wanfang Database and VIP Database. Meta-analysis, literature risk assessment and sensitivity analysis were conducted using R4.2.2 software and RevMan5.4 software.Results:A total of 4 eligible RCTs were found, including 155 patients. Meta-analysis showed that melatonin could reduce the mortality rate ( RR=0.336, 95% CI0.157-0.718, P=0.005) and white blood cell count in HIE infants ( MD=-1.74, 95% CI -3.404--0.079, P=0.040). Sensitivity analysis showed that the Meta-analysis results were generally stable after excluding the studies one by one. Conclusions:Current evidence shows that melatonin can reduce mortality in HIE infants. However, the included studies have high risk of bias and small sample sizes. More high-quality studies are still needed.

Effects of Different Pellet Feed Hardness on Growth and Reproduction, Feed Utilization Rate, and Environmental Dust in Laboratory Mice / 实验动物与比较医学

Objective To study the effects of different pellet feed hardness on the growth and reproduction, feed utilization rate, and environmental dust in laboratory mice.Methods One hundred of fifty 50 3-week-old SPF-grade C57BL/6JGpt and 150 ICR laboratory mice were randomly divided into three groups, with an equal number of males and females. They were fed diets with different hardness of 18.62 kg, 23.15 kg, and 27.89 kg. Body weight, feed utilization rate, and dust levels in cages were recorded and calculated for mice aged 3-10 weeks. Forty-five 6-week-old male mice and ninety 4-week-old female mice from each strain were randomly divided into three groups and fed pellet feeds with three different hardness levels. After 2 weeks of adaptation to the same hardness feed, the mice were paired at a 1∶2 male-to-female ratio and monitored for reproductive data for 3 months.Results At the age of 4 weeks, the body weight of male C57BL/6JGpt mice in 23.15 kg group was significantly higher than that in the 18.62 kg and 27.89 kg groups (P<0.01), and the body weight of females in the 18.62 kg group was significantly higher than that in the 27.89 kg group (P<0.05). There was no significant difference in body weight among ICR mice aged 3-10 weeks across different feed hardness groups (P>0.05). For both strains, feed utilization rate for males was higher than that for females across different feed hardness groups at all weeks of age (P<0.01). Compared to the 27.89 kg group, both the 18.62 kg and 23.15 kg groups showed a significant increase in the 50-mesh dust levels in cages for both strains aged 4-8 weeks (except for 7-week-old C57BL/6JGpt mice) (P<0.05). For both C57BL/6JGpt and ICR mice, there was no significant difference in basic reproductive performance such as interval between the first litter and the monthly production index among the three feed hardness groups during the experimental period (P>0.05). However, the monthly production index of C57BL/6JGpt mice first increased and then decreased with the increase of feed hardness, while that of ICR mice increased with increasing feed hardness, though these differences were not statistically significant (P>0.05).Conclusion Different strains and genders had different tolerance to feed hardness. C57BL/6JGpt mice are more adapted to lower hardness feeds, while ICR mice are better suited to slightly higher hardness feeds.

Effect of fenofibrate on the expression of miR-26a-5p/PTEN in retinal neurons of diabetic mice / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study the protective effect of fenofibrate on diabetic retinal neurodegeneration and observe its effect on miR-26a-5p and its target gene PTEN in the retinal of diabetic mice.METHODS: Diabetic mice models were established and they were gavaged by fenofibrate. H&#x0026;#x0026; E staining and transmission electron microscopy were used to observe the impairments of retinal neurons. Real-time PCR was used to examine the expression of miR-26a-5p, and Western blotting was employed to measure the expression of phosphatase and tensin homologue(PTEN)in the retina of diabetic mice. The expression level of nuclear factor-κB(NF-κB), interleukin-1β(IL-1β)and the morphology of neural tissues were observed.RESULTS: When compared with the diabetic mice, fenofibrate significantly attenuated the damage to retinal ganglion cells and the atrophy of retinal nerve fiber layer. While the level of miR-26a-5p was increased and the levels of PTEN and inflammatory mediators were significantly decreased in the retina of fenofibrate treated diabetic mice, with significant statistical significance(P&#x0026;#x003C;0.05).CONCLUSIONS: Fenofibrate protects against diabetic retinal neurodegeneration by upregulating miR-26a-5p and inhibiting PTEN, attenuating the inflammatory response and alleviating retinal cell injury.

FOXA1 prolongs S phase and promotes cancer progression in non-small cell lung cancer through upregulation of CDC5L and activation of the ERK1/2 and JAK2 pathways.

Non-small cell lung cancer (NSCLC) causes high mortality worldwide; however, its molecular pathways have not been fully investigated. The relationship between FOXA1 and CDC5L as well as their roles in NSCLC have not been comprehensively studied. Clinical tissues were collected from 78 NSCLC patients for clinical studies. The BEAS-2B human normal lung epithelial cell line and the A549, Calu-3, H526 and H2170 human NSCLC cell lines were used for in vitro studies. sh-FOXA1 and oe-CDC5L constructs were used to generate knockdown and overexpression models, respectively. The CCK-8 assay was used to analyze cell viability. The cell cycle and apoptosis were evaluated by flow cytometry analysis. The relationship between FOXA1 and CDC5L was demonstrated using dual-luciferase and ChIP assays. Gene levels were examined via immunohistochemistry, qRT-PCR and western blot analysis. FOXA1 levels were increased in NSCLC clinical tissues and cell lines. Depletion of FOXA1 increased the apoptosis rate and increased the proportion of cells in G2/M phase. In addition, we demonstrated that FOXA1 was directly bound to the promoter of CDC5L and that depletion of FOXA1 inhibited CDC5L expression. Overexpression of CDC5L induced ERK1/2 phosphorylation, induced JAK2 phosphorylation, inhibited cell apoptosis, prolonged S phase, and significantly reversed the effects of FOXA1 knockdown on the progression of NSCLC. The present study demonstrated that FOXA1 prolongs S phase and promotes NSCLC progression through upregulation of CDC5L and activation of the ERK1/2 and JAK2 pathways.

Analysis of risk factors associated with lower extremity venous thromboembolism after transurethral resection of prostate / 国际外科学杂志

Objective:To investigate the risk factors of lower extremity venous thromboembolism (VTE) after transurethral resection of prostate (TURP) in patients with prostatic hyperplasia.Methods:The clinical data of 464 patients with prostatic hyperplasia who underwent TURP in Beijing Friendship Hospital, Capital Medical University from July 2018 to August 2022 were collected retrospectively. Including basic information, prostate volume, operation time, Caprini score, plasma D-dimer level, postoperative complications and so on. They were divided into two groups according to whether lower extremity VTE occurs: VTE group ( n=25) and non-VTE group ( n=439). The potential risk factors of lower extremity VTE were determined by univariate analysis and multivariate Logistic regression analysis, the risk prediction model was established, and the nomogram was drawn, the internal verification of Bootstrap was carried out, the correction curve was made, and the prediction ability of the model was verified by consistency index (C-index) and R2. Results:Among 464 patients, the incidence of lower extremity VTE was 5.4% (25/464). A total of 1.9% of the patients were diagnosed with deep venous thromboembolism and no pulmonary thromboembolism occurred. There were significant differences in Caprini score, operation time, age, diabetes, smoking history and previous thrombus history between VTE group and non-VTE group. Univariate analysis showed that age, operation time, Caprini score, history of diabetes, smoking and previous history of thrombosis may be the risk factors of postoperative lower extremity VTE. Multivariate Logistic regression analysis showed that operation time ( OR=37.429, P=0.001) and Caprini score ( OR=3.306, P<0.001) were independent risk factors for postoperative lower extremity VTE. The risk of postoperative lower extremity VTE in patients with less than 60 minutes of operation was significantly lower than that in patients with more than 90 minutes ( OR=0.024, P<0.001), and the risk of postoperative lower extremity VTE in patients with Caprini scores of 4 and 5 was significantly lower than that of patients with 7 points ( OR=0.041 and 0.082, P=0.004 and 0.003). The nomogram was drawn according to the results of multivariate Logstic regression analysis. After internal verification, it was suggested that the nomogram has better prediction ability, C-index was 0.935, 95% CI: 0.906-0.965, R2 was 0.451. Conclusions:Caprini score and operation time are independent risk factors for lower extremity VTE after TURP of patients with prostatic hyperplasia. The nomogram model including operation time and Caprini score has good predictive efficiency and can help medical staff to predict the risk of lower extremity VTE after TURP.

Diagnostic Efficacy of Blood Inicators in the Diagnosis and Treatment of Gram-positive Cocci and Gram-negative Bacilli Infection / 昆明医科大学学报

Objective To explore the differences in the effectiveness of using different blood indicators individually,in combination,and for dynamic monitoring in the diagnosis,differential diagnosis,and prognosis of bacterial infections.Methods 1843 cases with infectious symptoms or signs from January 2015 to September 2022 at the People's Hospital of Yuxi City were selected as the case group,and 2298 uninfected individuals during the same period were selected as the control group.Blood indicators of the two groups were collected.Variables were grouped according to gender,age group,specimen type,etc.SPSS 24.0 and Medcalc 20.0 were used for statistical analysis.Results The individual diagnostic efficacy of various blood indicators for detecting infection ranges from 0.656 to 0.937.When used together,the efficacy ranges from 0.907 to 0.987.The efficacy of distinguishing between G+c and G-b in different specimens is as follows:when PCT is used alone in blood,the AUC is 0.875 for males and 0.769 for females.However,the individual diagnostic efficacy in male mucous secretions,sterile body fluids,and non-adult male sputum is all≤0.7.Yet,when used together,the efficacy is AUC(0.789,0.737,0.86)respectively.The dynamic monitoring of PCT,IL-6,CRP,WBC,and LAC in adult patients at 24 h,48 h,and 72 h after admission shows statistically significant differences in prognostic efficacy for G+c and G-b(P<0.05).Conclusions Blood indicators have a certain diagnostic value for determining whether there is a bacterial infection,and there are gender differences.The combined use of these indicators is more effective.The diagnostic value of using blood indicators alone or in combination for distinguishing between G+c and G-b in different types of specimens varies.The use of PCT alone in blood specimens is the most effective.For adult males,the combined use of body surface mucous secretions and sterile body fluids is most effective,while for underage males,the combined use of sputum is most effective.The combined use for females is not effective.Dynamic monitoring of PCT,CRP,IL-6,LAC,and WBC has a high value for evaluating the prognosis and therapeutic effect of infections.The evaluation of G+c infection is most effective at 24 hours for IL-6,and for G-b infection,it is most effective at 72 hours for PCT.

Analysis of pathological regularity and related risk factors of retinal nerve in-jury in patients with diabetes mellitus / 眼科新进展

Objective To observe the thickness changes in the peripapillary retinal nerve fiber layer(RNFL)and the ganglion cell-inner plexiform layer(GC-IPL)in the macular region,so as to analyze the pathological rules of retinal nerve injury in diabetes retinopathy(DR)patients and explore the related risk factors.Methods A total of 164 patients(164 eyes)with type 2 diabetes who visited the Department of Ophthalmology and Department of Endocrinology of Shaanxi Pro-vincial People's Hospital from January 1,2017 to January 1,2018 were selected as the subjects.According to the condition of concomitant DR,these subjects were divided into three groups:non-DR(NDR)group(56 eyes of 56 patients),mild non-proliferative DR(NPDR)group(53 eyes of 53 patients)and moderate NPDR group(55 eyes of 55 patients).Healthy individuals who underwent physical examinations in the same period were selected as the control group(50 eyes of 50 pa-tients).Optical coherence tomography and optical coherence tomography angiography were used to measure the peripapil-lary RNFL,macular GC-IPL,and macular vessel density(VD)of all subjects.Comparison among groups and correlation analysis were conducted on the above retinal nerve injury indicators.Results Compared with the control group and NDR group,the average,upper and lower peripapillary RNFL in the mild NPDR group and moderate NPDR group were signifi-cantly thinner,and the differences were statistically significant(all P＜0.05).The differences in macular GC-IPL thickness at the average,upper,upper temporal,lower temporal,lower,lower nasal,and upper nasal regions in all groups were sta-tistically significant(all P＜0.05);pairwise comparisons showed that compared with the control group,the GC-IPL thick-ness in each quadrant of the macular area of patients in the NDR group,mild NPDR group and moderate NPDR group de-creased significantly(all P＜0.05),with the upper GC-IPL thinning being the most significant;compared with the NDR group,the GC-IPL thickness in the upper,average,and upper temporal macular area of patients with mild NPDR decreased significantly(all P＜0.05);compared with the mild NPDR group,the GC-IPL thickness in the upper macular area was thin-ner in the moderate NPDR group,and the difference was statistically significant(P＜0.05).There were statistically signifi-cant differences in the average and inner ring VDs in the macular area among the groups(both P＜0.05).The correlation analysis results showed that there was a significantly positive correlation between the peripapillary RNFL thickness and the average VD in the macular area(r=0.517,P＜0.01),while the average GC-IPL thickness in the macular area was weakly positively correlated with the average VD in the macular area(r=0.279,P＜0.01).Conclusion The peripapillary RNFL thickness objectively reflects the degree of retinal neuron injury,and is a key index to evaluate the degree of retinal nerve injury in diabetes patients.

Relationship between ATAD3A expression level in gastric cancer tissue and chemotherapy sensitivity and prognosis / 中国基层医药

Objective:To investigate the relationship between ATPase Family AAA Domain Containing 3A (ATAD3A) expression level in gastric cancer tissue and chemotherapy sensitivity and prognosis.Methods:Eighty-six patients with advanced gastric cancer admitted to Shandong Second Rehabilitation Hospital from June 2020 to July 2021 were included in this study. Gastric cancer tissue and paracancer tissue samples were collected. ATAD3A expression level in gastric cancer tissue was detected using immunohistochemical staining with the SP method. ATAD3A expression was compared between gastric cancer tissue and paracancer tissue. The relationship between ATAD3A expression and clinical pathological parameters was analyzed. The relationship between ATAD3A expression level in gastric cancer tissue and chemotherapy sensitivity and prognosis was analyzed.Results:The ATAD3A-positive expression rate in the gastric cancer tissue was 75.58% (65/86), which was significantly higher than 43.02% (37/86) in the paracancer tissue ( χ2 = 18.89, P < 0.001). The expression level of ATAD3A in gastric cancer tissues was not correlated with gender, age, tumor diameter, clinical stage or lymph node metastasis (all P > 0.05). The proportion of low differentiation and distant metastasis in patients with ATAD3A-positive expression was significantly higher than that in patients with ATAD3A-negative expression ( χ2 = 5.71, 6.17, both P < 0.05). The total response rate of chemotherapy in patients with ATAD3A-positive expression was 60.00% (39/65), which was significantly lower than 85.71% (18/21) in patients with ATAD3A-negative expression ( χ2 = 4.55, P = 0.033). Of 86 patients, 59 were sensitive to paclitaxel and 56 to capecitabine. The sensitivity of paclitaxel and capecitabine in the ATAD3A-positive group was lower than that in the blank control group ( χ2 = 6.17, 5.19, both P < 0.05). After 1 year of follow-up, the cumulative survival rate in patients with ATAD3A-positive expression was 43.08% (28/65), which was significantly lower than 71.43% (15/21) in patients with ATAD3A-negative expression ( χ2 = 5.24, P < 0.05). The survival time of patients with ATAD3A-positive expression was (8.47 ± 2.13) months, which was significantly shorter than (13.62 ± 1.49) months for patients with ATAD3A-negative expression ( t = 6.29, P < 0.05). Cox multivariate regression analysis showed low differentiation ( HR = 6.22, 95% CI: 1.537-25.240), distant metastasis ( HR = 2.57, 95% CI: 1.396-4.742), and positive expression of ATAD3A ( HR = 10.60, 95% CI: 2.631-42.715) were independent factors that affect the survival time of patients with gastric cancer after chemotherapy ( P < 0.05). Conclusion:ATAD3A is expressed in gastric cancer tissue. Its expression level is closely related to chemotherapy sensitivity and prognosis. It provides an important reference value for the evaluation of chemotherapy efficacy and prognosis.

Regulation of SIGIRR expression mechanism in human renal tubular epithelial cells by nuclear transcription factor NF - κB / 安徽医科大学学报

Objective @#To investigate the molecular mechanisms underlying the feedback regulation of single immunoglobin interleukin-1 related receptor ( SIGIRR) expression by the nuclear factor kappa-κB ( NF-κB) in human renal tubular epithelial cells ( HKC) ．@*Methods @#The pLNCX2-G418-SIGIRR overexpression vector was constructed by molecular cloning，and the SIGIRR overexpression cells and control cells were constructed by infecting HKC cells after packaging with PT67 cells．Using IL-1 β induction，Western blot verified that overexpression of SIGIRR inhibited NF-κB activation．After using NF-κB blocker and interfering with NF-κB activity ，immunofluorescence assay verified that activated NF-κB regulated SIGIRR expression． Online tools predicted the presence of NF-κB binding sites in the SIGIRR promoter region．The SIGIRR promoter sequence containing the binding site was obtained from within human genomic DNA by molecular cloning，ligated to the luciferase vector pGL3-Luc，constructed pGL3-Luc-SIGIRR , and mutated the binding site．The luciferase reporter gene assay and chromatin immunopre- cipitation technique ( ChIP) were used to jointly verify that activated NF-κB could bind to the SIGIRR promoter region to regulate SIGIRR gene expression. @*Results @#The results showed that the constructed pLNCX2-G418-SIGIRR retroviral vector was verified by enzymatic digestion and sequencing to be identical to the coding sequence of the SIGIRR gene for comparison，the recombinant and control vectors were transferred into HKC cells after viral packaging，and the HKC / SIGIRR experimental and HKC / Co control cell lines were successfully constructed at the mRNA and protein levels of SIGIRR expression differences were statistically significant (P＜0．05，P＜0. 001) ．Overexpression of SIGIRR cell groups reduced IL-1 β-induced NF-κB activation compared to control cells (P＜0. 001) . SIGIRR expression was downregulated after inhibition of NF-κB activation and interference with NF-κB expression. After extracting human genomic DNA ，the SIGIRR target promoter sequence was obtained by molecular cloning method and linked to the vector，and the pGL3-Luc-SIGIRR luciferase vector was successfully constructed and targeted to mutate the vector，which was verified to be identical to the target sequence by digestion and sequencing. The luciferase reporter gene assay and CHIP assay confirmed that NF-κB could bind to SIGIRR promoter region and regulate SIGIRR expression．@*Conclusion@#It has been verified that SIGIRR can influence the activation of NF-κB in HKC cells，and activated NF-κB can bind to the promoter region of SIGIRR and regulate the gene expression changes of SIGIRR , forming a feedback system to control the over-activation of NF-κB.

Research progress in the effects of intraocular pressure-lowering drugs on the ocular surface of glaucoma patients / 国际眼科杂志(Guoji Yanke Zazhi)

Glaucoma is a chronic optic neuropathy that affects the retinal ganglion cells, characterized by optic disc atrophy, visual field defects, and visual acuity loss. Since glaucoma is a chronic disease, long-term use of topical intraocular pressure-lowering medications often leads to ocular surface diseases, thus reducing medication adherence and ultimately affecting treatment efficacy. Currently, topical intraocular pressure-lowering medications include prostaglandin derivatives, β-adrenergic blockers, α-adrenergic agonists, topical carbonic anhydrase inhibitors, and cholinergic drugs. This article provides a comprehensive review of the effects and related mechanisms of these five antiglaucoma medications on the ocular surface of glaucoma patients and offers preventative measures for the protection of ocular surface in glaucoma patients.

A cross-sectional study of enterovirus nucleic acid test with throat swabs for term late neonates during coronavirus disease 2019 / 中国当代儿科杂志

OBJECTIVES@#To investigate the positive rate of enterovirus (EV) nucleic acid in throat swabs of term late neonates hospitalized during the coronavirus disease 2019 (COVID-19) epidemic and the clinical characteristics of the neonates.@*METHODS@#A single-center cross-sectional study was performed on 611 term late infants who were hospitalized in the neonatal center from October 2020 to September 2021. Throat swabs were collected on admission for coxsackie A16 virus/EV71/EV universal nucleic acid testing. According to the results of EV nucleic acid test, the infants were divided into a positive EV nucleic acid group (8 infants) and a negative EV nucleic acid group (603 infants). Clinical features were compared between the two groups.@*RESULTS@#Among the 611 neonates, 8 tested positive for EV nucleic acid, with a positive rate of 13.1‰, among whom 7 were admitted from May to October. There was a significant difference in the proportion of infants contacting family members with respiratory infection symptoms before disease onset between the positive and negative EV nucleic acid groups (75.0% vs 10.9%, P<0.001). There were no significant differences between the two groups in demographic data, clinical symptoms, and laboratory test results (P>0.05).@*CONCLUSIONS@#There is a certain proportion of term late infants testing positive for EV nucleic acid in throat swabs during the COVID-19 epidemic, but the proportion is low. The clinical manifestations and laboratory test results of these infants are non-specific. Transmission among family members might be an important cause of neonatal EV infection.

High expression of VARS promotes the growth of multiple myeloma cells by causing imbalance in valine metabolism / 中南大学学报(医学版)

OBJECTIVES@#Multiple myeloma (MM) is a plasma cell malignancy occurring in middle and old age. MM is still an incurable disease due to its frequent recurrence and drug resistance. However, its pathogenesis is still unclear. Abnormal amino acid metabolism is one of the important characteristics of MM, and the important metabolic pathway of amino acids participates in protein synthesis as basic raw materials. Aminoacyl transfer ribonucleic acid synthetase (ARS) gene is a key regulatory gene in protein synthesis. This study aims to explore the molecular mechanism for ARS, a key factor of amino acid metabolism, in regulating amino acid metabolism in MM and affecting MM growth.@*METHODS@#The corresponding gene number was combined with the gene expression profile GSE5900 dataset and GSE2658 dataset in Gene Expression Omnibus (GEO) database to standardize the gene expression data of ARS. GSEA_4.2.0 software was used to analyze the difference of gene enrichment between healthy donors (HD) and MM patients in GEO database. GraphPad Prism 7 was used to draw heat maps and perform data analysis. Kaplan-Meier and Cox regression model were used to analyze the expression of ARS gene and the prognosis of MM patients, respectively. Bone marrow samples from 7 newly diagnosed MM patients were collected, CD138+ and CD138- cells were obtained by using CD138 antibody magnetic beads, and the expression of ARS in MM clinical samples was analyzed by real-time RT-PCR. Human B lymphocyte GM12878 cells and human MM cell lines ARP1, NCI-H929, OCI-MY5, U266, RPMI 8266, OPM-2, JJN-3, KMS11, MM1.s cells were selected as the study objects. The expression of ARS in MM cell lines was analyzed by real-time RT-PCR and Western blotting. Short hairpin RNA (shRNA) lentiviruses were used to construct gene knock-out plasmids (VARS-sh group). No-load plasmids (scramble group) and gene knock-out plasmids (VARS-sh group) were transfected into HEK 293T cells with for virus packaging, respectively. Stable expression cell lines were established by infecting ARP1 and OCI-MY5 cells, and the effects of knockout valyl-tRNA synthetase (VARS) gene on proliferation and apoptosis of MM cells were detected by cell counting and flow cytometry, respectively. GEO data were divided into a high expression group and a low expression group according to the expression of VARS. Bioinformatics analysis was performed to explore the downstream pathways affected by VARS. Gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) and high performance liquid chromatography (HPLC) were used to detect the valine content in CD138+ cells and ARP1, OCI-MY5 cells and supernatant of knockdown VARS gene in bone marrow samples from patients, respectively.@*RESULTS@#Gene enrichment analysis showed that tRNA processing related genes were significantly enriched in MM compared with HD (P<0.0001). Further screening of tRNA processing-pathway related subsets revealed that cytoplasmic aminoacyl tRNA synthetase family genes were significantly enriched in MM (P<0.0001). The results of gene expression heat map showed that the ARS family genes except alanyl-tRNA synthetase (AARS), arginyl-tRNA synthetase (RARS), seryl-tRNA synthetase (SARS) in GEO data were highly expressed in MM (all P<0.01). With the development of monoclonal gammopathy of undetermined significance (MGUS) to MM, the gene expression level was increased gradually. Kaplan-Meier univariate analysis of survival results showed that there were significant differences in the prognosis of MM patients in methionyl-tRNA synthetase (MARS), asparaginyl-tRNA synthetase (NARS) and VARS between the high expression group and the low expression group (all P<0.05). Cox regression model multivariate analysis showed that the high expression of VARS was associated with abnormal overall survival time of MM (HR=1.83, 95% CI 1.10 to 3.06, P=0.021). The high expression of NARS (HR=0.90, 95% CI 0.34 to 2.38) and MARS (HR=1.59, 95% CI 0.73 to 3.50) had no effect on the overall survival time of MM patients (both P>0.05). Real-time RT-PCR and Western blotting showed that VARS, MARS and NARS were highly expressed in CD138+ MM cells and MM cell lines of clinical patients (all P<0.05). Cell counting and flow cytometry results showed that the proliferation of MM cells by knockout VARS was significantly inhibited (P<0.01), the proportion of apoptosis was significantly increased (P<0.05). Bioinformatics analysis showed that in addition to several pathways including the cell cycle regulated by VARS, the valine, leucine and isoleucine catabolic pathways were upregulated. Non-targeted metabolomics data showed reduced valine content in CD138+ tumor cells in MM patients compared to HD (P<0.05). HPLC results showed that compared with the scramble group, the intracellular and medium supernatant content of ARP1 cells and the medium supernatant of OCI-MY5 in the VARS-shRNA group was increased (all P<0.05).@*CONCLUSIONS@#MM patients with abnormal high expression of VARS have a poor prognosis. VARS promotes the malignant growth of MM cells by affecting the regulation of valine metabolism.

Effect of IoT-based power cycling and quadriceps training on pain and function in patients with knee osteoarthritis: A randomized controlled trial protocol.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic musculoskeletal disease affecting the entire joint. Exercise therapy is the core treatment plan for non-surgical treatment of KOA, and tele-rehabilitation is also applied to KOA, but there is a lack of research on the comparison of pain and function recovery between different exercise methods combined Internet respectively. The study aims to compare the effects of power cycling and quadriceps training combined with online guidance separately on KOA mitigation of pain, recovery of function, quality of life, and adherence of participants in the community, compared to the control group. METHODS: This study is a single-blind, 12-week parallel randomized controlled trial. Seventy-two participants aged ≥ 50 years with KOA will be randomized into either the power cycling group, the quadriceps group or the control group. The intervention will be performed three times per week during 12 weeks. Outcome measures will be assessed at baseline, and at 4, 8, and 12 weeks after allocation. The primary outcome will be self-reported pain, assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. Secondary outcomes will include mitigation of knee pain, quality of life, improvement of functional physical performance, adherence of participants. DISCUSSION: By summarizing the study's strengths and limitations, this trial results may guide tele-rehabilitation of KOA in the community.Trial registration: The study was registered in the clinical trial registry ChiCTR2200059255, 27/04/2022.

Design and fabrication of diffraction grating with optimized efficiency for transient grating spectroscopy.

Transient grating spectroscopy (TGS) based on diffraction gratings is a powerful optical method for studying the transport of energy carriers such as phonons and electrons. The diffraction grating in a TGS system is a key component to form a large-area interference pattern, i.e., transient grating, and to study the mean free path distribution of energy carriers. In this work, a design method for polarization-insensitive diffraction gratings with periods in the range 2-50 µm for TGS by a combination of rigorous coupled wave analysis and genetic algorithm was discussed. The method was tested for pump/probe wavelength of 515/532 or 1030/808 nm. Each ±1st diffraction order carries 35%-40% of the incident energy and the diffraction efficiencies of the other orders are lower than 10%. The optimized diffraction gratings were fabricated by a combination of photolithography and inductively coupled plasma etching, with the processing parameters introduced in detail, and their optical characteristics were evaluated. Finally, as a demonstration, the diffraction gratings for 1030/808 nm were applied to TGS to study the thermal transport properties of Ge. This work provides a useful guide for future applications and the development of TGS.

Distress, support and psychological resilience of psychiatric nurses as second victims after violence: A cross-sectional study.

AIM: The aim is to explore the impact of violence and psychological resilience on psychiatric nurses as second victims. BACKGROUND: Workplace violence is a public health concern, seriously influencing medical staff's physical and mental health. However, few pieces of research have concentrated on psychiatric nurses as second victims. METHOD: The socio-demographic data, violence-related data, psychological resilience scale, the Chinese version of the Second Victim Experience and Support Tool were applied to conduct a cross-sectional survey on nurses from psychiatric hospitals. The multiple linear regression model identified significant variables associated with violence-related injury and resilience. RESULTS: A total of 683 nurses completed the survey, of whom 88.3% were women. The average scores of the second victims' experience and support, support and distress were 3.45 ± 0.43, 3.71 ± 0.57 and 3.19 ± 0.67, respectively. Physical violence, psychological violence, psychological influence and nursing work environment were positively correlated with the experience and support of the second victims, and innocuous violence was a negative factor, which explains 20.6% of the variation. Moreover, physical injury, nursing work environment, resilience restructuring, physical violence, psychological violence, psychological impact and disagreement about the existence of violence explained 14.8% of the distress. The innocuous violence, psychological violence and nursing work environment explained 46.2% of the support. CONCLUSIONS: Our findings suggest that nurses who are second victims after the violence mainly suffer from severe psychological distress and receive the least support for the same. IMPLICATION FOR NURSING MANAGEMENT: The study provides clues to help nursing managers' emphasis on the distress and support of second victims and provides targeted intervention based on the relevant factors and these results. The article is a cross-sectional study of psychiatric nurses, which has been approved by the ethics committee of the hospital before the survey. All the nurses who participated in the survey have been informed and agreed.

Atomic-scale probing of heterointerface phonon bridges in nitride semiconductor.

Interface phonon modes that are generated by several atomic layers at the heterointerface play a major role in the interface thermal conductance for nanoscale high-power devices such as nitride-based high-electron-mobility transistors and light-emitting diodes. Here we measure the local phonon spectra across AlN/Si and AlN/Al interfaces using atomically resolved vibrational electron energy-loss spectroscopy in a scanning transmission electron microscope. At the AlN/Si interface, we observe various interface phonon modes, of which the extended and localized modes act as bridges to connect the bulk AlN modes and bulk Si modes and are expected to boost the phonon transport, thus substantially contributing to interface thermal conductance. In comparison, no such phonon bridge is observed at the AlN/Al interface, for which partially extended modes dominate the interface thermal conductivity. This work provides valuable insights into understanding the interfacial thermal transport in nitride semiconductors and useful guidance for thermal management via interface engineering.

MiR-421 promotes lipid metabolism by targeting PTEN via activating PI3K/AKT/mTOR pathway in non-small cell lung cancer.

Aims: We aim to investigate the effects of miR-421 on lipid metabolism in non-small cell lung cancer (NSCLC). Methods: The miR-421 expression and PTEN mRNA level in tumor tissues, adjacent normal tissues, human lung epithelial cells and NSCLC cell lines were detected with reverse transcription quantitative real-time PCR. Results: MiR-421 was increased, and PTEN was reduced remarkably in tumor tissues and NSCLC cell lines. Down-regulated miR-421 suppressed lipid accumulation, cell proliferation, migration and invasion, whereas overexpression of miR-421 had the opposite effects. MiR-421 directly targeted PTEN and negatively regulated PTEN expression. MiR-421 activated PI3K/AKT/mTOR pathway through regulating PTEN. Conclusion: MiR-421 promotes lipid metabolism through targeting PTEN via PI3K/AKT/mTOR pathway activation in NSCLC, indicating that miR-421 can be a latent therapeutic target for NSCLC.

Lay abstract Numerous miRNAs are dysregulated in lung cancer, which play vital roles in tumor progression. Currently, the alteration of lipid metabolism has been recognized as a critical hallmark of cancer. In the present study, we found that miR-421 targeted PTEN to promote lipid metabolism via activation of PI3K/AKT/mTOR signaling pathway in NSCLC. This study might provide a deeper insight into the prognostics strategies for lung cancer by understanding the specific mechanism of miR-421 in lipid metabolism.

Impact of various vaccine boosters on neutralization against Omicron following prime vaccinations with inactivated or adenovirus-vectored vaccine

Since the first report on November 24, 2021, the Omicron SARS-CoV-2 variant is now overwhelmingly spreading across the world. Two SARS-CoV-2 inactivated vaccines (IAVs), one recombinant protein subunit vaccine (PRV), and one adenovirus-vectored vaccine (AdV) have been widely administrated in many countries including China to pursue herd immunity. Here we investigated cross-neutralizing activities in 341 human serum specimens elicited by full-course vaccinations with IAV, PRV and AdV, and by various vaccine boosters following prime IAV and AdV vaccinations. We found that all types of vaccines induced significantly lower neutralizing antibody titers against the Omicron variant than against the prototype strain. For prime vaccinations with IAV and AdV, heterologous boosters with AdV and PRV, respectively, elevated serum Omicron-neutralizing activities to the highest degrees. In a mouse model, we further demonstrated that among a series of variant-derived RBD-encoding mRNA vaccine boosters, it is only the Omicron booster that significantly enhanced Omicron neutralizing antibody titers compared with the prototype booster following a prime immunization with a prototype S-encoding mRNA vaccine candidate. In summary, our systematical investigations of various vaccine boosters inform potential booster administrations in the future to combat the Omicron variant.

Clinical analysis of nonsyndromic cleft lip and palate in 109 patients living at high altitude / 中国基层医药

Objective:To analyze the risk factors and characteristics of nonsyndromic clef lip and palate living at high altitude, providing evidence for preventing cleft lip and palate.Methods:The clinical data of 109 Tibetan patients with nonsyndromic cleft lip and palate who received treatment in People's Hospital of Ganzi Tibetan Autonomous Prefecture between August 2016 and August 2020 were retrospectively analyzed.Results:The 109 patients with cleft lip and palate were aged 4 months to 48 years. The ratio of male to female patients was 1.42∶1. The ratio of male to female patients with simple cleft lip was 1.40∶1. The ratio of male to female patients with cleft lip and palate was 1.71∶1. The ratio of male to female patients with simple cleft palate was 1.3∶1. The mothers of all patients did not undergo prenatal examination and did not take folic acid during pregnancy. Eight patients (7.3%) had a family genetic history of cleft lip and palate. Two patients (1.8%) had consanguineous marriage within three generations. Seven patients (6.4%) took drugs in the first three months of pregnancy. One patient (0.9%) had malnutrition during pregnancy. Among 65 patients (59.1%) had simple cleft lip, 48 patients (73.8%) had incomplete cleft lip. Among 25 patients (22.9%) had simple cleft palate, 14 patients (56.0%) had incomplete cleft palate. Nineteen patients (17.2%) had cleft lip and palate. The number of patients with unilateral cleft lip with or without cleft palate was greater than that of patients with bilateral cleft lip with or without cleft palate. The number of patients with left cleft lip with or without cleft palate was greater than that of patients with right cleft lip with or without cleft palate. The ratio of the number of patients with unilateral cleft lip to the number of patients with bilateral cleft lip was 12∶1. The ratio of the number of patients with left cleft lip to the number of patients with right cleft lip was 1.9∶1. The ratio of the number of patients with unilateral cleft lip and palate to the number of patients with bilateral cleft lip and palate was 5.3∶1. The ratio of the number of patients with left cleft lip and palate to the number of patients with right cleft lip and palate was 2.8∶1. Twelve patients (63.2%) had complete cleft palate.Conclusion:Popularizing knowledge of pregnancy health care and strengthening pre-pregnancy and during-pregnancy examination can reduce the incidence of cleft lip and palate.