Objective:To study the clinical manifestations and genetic characteristics of neonatal-onset primary mitochondrial disease (PMD) caused by nuclear gene mutations.Methods:From May 2020 to March 2022, the clinical data, genetic results and follow-up information of neonates with PMD admitted to the Department of Neonatology of our two hospitals were retrospectively analyzed.Results:A total of 4 patients were enrolled, all with hyperlactatemia and metabolic acidosis. In case 1, the fetal cranial MRI showed agenesis of corpus callosum. In case 2, echocardiography after birth indicated hypertrophic cardiomyopathy. Whole exome sequencing found the following mutations: EARS2 nuclear gene c.1294C>T and c.971G>T variants, COA6 nuclear gene c.411_412insAAAG variant, ACAD9 nuclear gene c.1278+1G>A and c.895A>T variants, FOXRED1 nuclear gene c.1054C>T and c.3dup variants. Mitochondrial second-generation sequencing and multiplex ligation-dependent probe amplification showed no abnormalities. Cases 1 and 3 died during the neonatal period. Case 2 died at 2-year-and-2-month of age. Case 4 was followed up to 1 year of age with developmental delay.Conclusions:The main phenotypes of neonatal-onset PMD caused by nuclear gene mutations are hyperlactatemia, refractory metabolic acidosis and cardiomyopathy, which have a poor prognosis. Proactive genetic tests are helpful for early diagnosis.

Objective To screen Cuproptosis genes and characteristic genes for differential prognosis in acute mye-loid leukemia(AML)and explore their prognosis in AML as well as their biological roles and correlations in the immune and tumor microenvironment.Methods AML clinical,transcriptome,genomic,and copy number data were downloaded from three major databases,TCGA,GEO,and UCSC,and Cuproptosis genes were collected from published studies.From the perspective of multiomics,the effects of Cuproptosis gene and characteristic gene on survival,immunity,tumor microenvironment,stem cell correlation and drug sensitivity were studied by various bioinformatics methods,meta-analysis and secondary typing.Results One Cuproptosis gene was identified as a differential prognostic gene in AML and five characteristic genes were identified as influencing the prognosis of AML patients by influencing Cuproptosis,and a prognostic model was established.The differential genes were mainly concentrated in mitochondrial activity,REDOX enzyme and energy metabolism.In terms of immunity,macrophage M0,neutrophils,activated memory CD4 T cells and Tregs were positively correlated with risk score,while macro-phage M2,resting mast cells,immature CD4 T cells,helper follicular T cells and memory B cells were negatively correlated with risk score.In terms of tumor microenvironment,the immune cell score of the low-risk group was lower than that of the high-risk group,and in the total score,the tumor microenvironment score of the low-risk group was also lower than that of the high-risk group,indicating that the tumor purity of the high-risk group was lower than that of the low-risk group.However,there was no significant association between stem cells in the high-risk and low-risk groups,and a total of 14 drugs were found to be sensitive to treat AML.Conclusion Cuproptosis gene and characteristic gene are closely related to immune and tumor microenvironment in AML by constructing a prognostic model of AML.

Objective:To investigate the pathogenic role and possible mechanism of NADPH oxidase 4 (Nox4) in type 1 diabetic keratopathy mouse models.Methods:Forty Nox4 knockout ( Nox4-/-) heterozygous male mice were selected and 120 age- and sex-matched wild-type C57BL/6 ( Nox4+ /+ ) mice were selected as controls. Nox4-/- and Nox4+ /+ mice were randomized into diabetic group (DM group) and non-DM group by random number method.Type 1 DM model was established in DM groups by intraperitoneal injection of streptozotocin.The DM and non-DM groups of Nox4+ /+ mice were randomized into regular feed group and Nox4 inhibitor GKT137831 (GKT) supplementary feed group by random number method.At 16 weeks after modeling, tear secretion of mice in different groups was measured by the phenol red thread test.Corneal epithelial integrity was evaluated by fluorescent staining.Changes in corneal never fiber density were observed by the in vivo laser scanning confocal microscopy.Reactive oxygen species (ROS) products in corneal epithelium were assayed by CellROX staining.The expressions of E-Cadherin and nuclear factor-κB (NF-κB) proteins were detected by immunofluorescence staining.Central corneal nerve fiber density was examined by flatmount staining with TUBB3 antibody.The use and care of laboratory animals complied with ARVO statement.The study protocol was approved by Laboratory Animal Care Committee of Xi'an Jiaotong University (No.XJTULAC201301). Results:In Nox4+ /+ mice, the tear secretion was (2.40±1.18)mm/minute in DM group, which was significantly less than (5.30±1.02)mm/minute in non-DM group ( P<0.01).The tear secretion was (4.19±0.63)mm/minute in DM group of Nox4-/- mice, which was significantly more than that in DM group of Nox4+ /+ mice ( P<0.05).Significant difference was found between (2.23±0.83)mm/minute of regular feed group and (4.02±0.71)mm/minute of GKT supplementary feed group ( P<0.01).In Nox4+ /+ mice, the DM group showed significantly increased corneal staining score, reduced corneal nerve fiber density, increased fluorescence intensity of ROS in corneal epithelium, weakened fluorescence intensity of E-Cadherin protein expression, and enhanced fluorescence of NF-κB protein expression compared with non-DM group.In Nox4-/- mice and mice fed with GKT supplementary feed, the increased fluorescence of ROS and decreased fluorescence of E-Cadherin protein expression were seen in the corneal epithelium of the DM groups compared with non-DM groups.In Nox4-/- mice and mice fed with GKT supplementary feed, NF-κB protein fluorescence was weak in corneal epithelial cells in DM groups, which was similar to that in non-DM groups.Immunofluorescence staining of corneal flatmount showed that the density of TUBB3-stained nerve fibers in DM group of Nox4+ /+ mice was significantly lower than that in non-DM group of Nox4+ /+ mice, and there was no significant reduction of nerve fibers in the corneal stromal layer in DM group of Nox4-/- mice or mice fed with GKT supplementary feed. Conclusions:Nox4 is involved in the pathogenic process of diabetic keratopathy, and its mechanism may be related to oxidative stress-induced aggregation of ROS products and activation of NF-κB-mediated inflammatory responses.

In the context of the emphasis on the claims of multiple subjects in fourth-generation educational evaluation, the subjective experience of students has gradually become one of the key contents of educational evaluation. However, there is still a vague understanding of the conceptual source, specific definition, and measurement indicators of the student experience theory, and a more systematic theoretical system has not yet been formed. With the UE user experience thinking in the business field as the core meta-theory, this article integrates value-added evaluation and the idea of three-source flow, elaborates on the core concept connotation of compound student experience teaching evaluation, and builds a five-dimensional evaluation model for student experience with "aesthetic experience, interactive experience, emotional experience, behavioral experience, and discursive experience" as the first-level indicators based on literature research, expert interviews, and multi-round group discussions. It is hoped that student evaluation will force teachers to improve the contents and form of teaching and help to achieve breakthrough reform of the teaching system as a whole.

Objective To construct a prognosis prediction model of primary liver cancer after surgical treatment based on synthetic minority over-sampling technique(SMOTE)algorithm and machine learning model.Methods A retrospective cohort study was conducted on 4 297 patients with primary liver cancer from the surveillance,epidemiology,and end results(SEER)database.One-Hot Encoding and Multiple Imputation were used to preprocess the collect data,and SMOTE algorithm was employed to solve the imbalance of data categories.The obtained clinical variables were included in the machine learning model.Based on decision tree(DT),random forest(RF),gradient boosting decision tree(GBDT)and eXtreme Gradient Boosting(XGBoost),a prognostic prediction model(SMOTE+DT/RF/GBDT/XGBoost)was build,and then the best prediction model was determined by comparing the performance of various models.Finally,a prognostic analysis system for primary liver cancer was developed based on the optimal model,which was then visualized.Results The combination model SMOTE+RF showed the best predictive performance,with higher area under the curve(0.895),accuracy(0.811)and precision(0.806)than those of other models in receiver operating characteristic curve(ROC)analysis.Conclusion The SMOTE+RF prognostic prediction model can effectively predict the survival outcome of patients with primary liver cancer.

Objective:To observe the clinical efficacy of neck Gongfa exercise in intervening people at high risk for cervical spondylosis. Methods:A total of 212 participants from 8 companies at high risk for cervical spondylosis were divided into two groups using the random number table method,with 105 participants in the control group receiving health education and 107 participants in the trial group receiving an additional neck Gongfa exercise.After successive 3-month interventions,the two groups were compared in terms of cervical soft tissue tension and neck disability index(NDI)score.The incidence of cervical spondylosis was observed 3 months later. Results:During the process,10 cases dropped out in the trial group,and the control group had 9 dropout cases.After the intervention,the cervical soft tissue tension value and NDI score improved in both groups(P<0.05)and showed significant differences between the two groups(P<0.05).At the 3-month follow-up,the trial group had a lower incidence rate of cervical spondylosis than the control group(P<0.05). Conclusion:For people at high risk for cervical spondylosis,neck Gongfa exercise can effectively improve cervical soft tissue tension and motor dysfunction and lower the incidence of cervical spondylosis in the short run.

Objective To investigate the effect of probiotics in patients with chronic heart failure (CHF) and its impact on intestinal microecology. Methods A total of 112 patients with CHF were selected as research subjects and randomly divided into study group and control group, with 56 patients in each group. The control group received angiotensin-converting enzyme inhibitors (ACEI) combined with angiotensin Ⅱ receptor blockers (ARB) for treatment, while the study group received bifidobacterium viable capsules on the basis of treatment in the control group. The levels of myocardial fibrosis markers[type Ⅰ collagen precursor C-propeptide (PⅠCP), type Ⅲ collagen precursor N-propeptide (PⅢNP), PⅠCP/PⅢNP, type Ⅰ collagen carboxyl-terminal peptide (ⅠCTP)], cardiac function indicators[leftventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular end-systolic volume (LVESV)], intestinal flora abundance, plasma trimethylamine oxide (TMAO) levels, and serum tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) levels were measured in both groups. The therapeutic effects, drug safety, re-hospitalization rate, and mortality rate within 3 months after discharge were observed in both groups. Results The total effective rate in the study group was 71.43 %, which was higher than 51.79 % in the control group (P < 0.05). After treatment, the LVEF in the study group was higher than that in the control group, while LVEDD, LVESD, and LVESV were lower than those in the control group (P < 0.05). After treatment, the PⅠCP/PⅢNP in the study group was higher than that in the control group, while the ⅠCTP level was lower than that in the control group (P < 0.05). After treatment, the abundances of Proteobacteria, Actinobacteria, Firmicutes, and Fusobacteria in the study group were lower than those in the control group, while the abundance of Bacteroidetes was higher than that in the control group (P < 0.05). After treatment, the levels of TMAO, TNF-α, and IL-1β in the study group were lower than those in the control group (P < 0.05). No serious adverse reactions occurred in either group after treatment. Within 3 months after discharge, the re-hospitalization rate in the study group was 12.50 %, which was lower than 30.36 %in the control group (P < 0.05). The mortality rates in the study group and the control group were 1.79 % and 7.14 %, respectively, but no statistically significant difference was observed(P>0.05). Conclusion The combination of probiotics with ACEI and ARB can effectively reduce myocardial fibrosis in patients with CHF and improve intestinal microecology and prognosis.

As a representative chemotherapeutic drug, docetaxel (DTX) has been used for breast cancer treatment for decades. However, the poor solubility of DTX limits its efficacy, and the DTX based therapy increases the metastasis risk due to the upregulation of C-X-C chemokine receptor type 4 (CXCR4) expression during the treatment. Herein, we conjugated CXCR4 antagonist peptide (CTCE) with DTX (termed CTCE-DTX) as an anti-metastasis agent to treat breast cancer. CTCE-DTX could self-assemble to nanoparticles, targeting CXCR4-upregulated metastatic tumor cells and enhancing the DTX efficacy. Thus, the CTCE-DTX NPs achieved promising efficacy on inhibiting both bone-specific metastasis and lung metastasis of triple-negative breast cancer. Our work provided a rational strategy on designing peptide-drug conjugates with synergistic anti-tumor efficacy.

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC₅₀: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC₅₀: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.

Objective:To observe the effect of Yi Jin Jing(Sinew-transforming Qigong Exercises)intervention on anxiety in asymptomatic patients with Corona Virus Disease 2019(COVID-19)infection during quarantine.Methods:A total of 160 asymptomatic patients with COVID-19 infection were stratified by gender and divided into an observation group and a control group by the stratified randomization method,with 80 cases in each group.The control group was given basic nursing in the cabin,and the observation group was given additional Yi Jin Jing exercises once a day,20 min each time,and trained continuously until 1 d before leaving the cabin.The Hamilton anxiety scale(HAMA)score was compared between the two groups.Results:A total of 154 cases were included for data analysis in this study,including 74 cases in the observation group and 80 cases in the control group.After intervention,the HAMA scores in both groups increased(P<0.05),while the score in the observation group was lower than that in the control group(P<0.05).In the control group,the HAMA score of females after intervention was higher than that of males.The scores of mental anxiety and somatic anxiety in both groups were higher than those before intervention,while the score of mental anxiety in the observation group was significantly lower than that in the control(P<0.05).However,there was no statistical difference in the somatic score between the two groups(P>0.05).Conclusion:Patients with COVID-19 infection will get anxious during quarantine.Yi Jin Jing exercise can effectively reduce the aggravation of anxiety in asymptomatic patients with COVID-19 infection during concentrated quarantine.