Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

Objective:To construct an evaluation index system for the quality of hospice care services, so as to provide scientific basis for evaluating the clinical practice quality of hospice care in China.Methods:Based on theories related to medical quality, a primary item pool was constructed through literature analysis. From November to December 2023, the Delphi method was used to conduct two rounds of consultation with 18 hospice care experts from 10 provinces and municipalities directly under the central government, to establish the indicators at all levels of the evaluation index system. The weights and combination weights of indicators at all levels were calculated using the analytic hierarchy process. The expert's positive coefficient was expressed as the effective response rate of the questionnaire. The degree of expert authority was expressed as the expert authority coefficient. The degree of coordination of expert opinions was represented by Kendall's W and coefficient of variation. Results:In the two rounds of expert consultation, the effective response rates of the questionnaires were 88.89% (16/18) and 93.75% (15/16), the expert authority coefficients were 0.885 and 0.897, the kendall's W values of the overall indicators were 0.152 and 0.191 ( P<0.01), and the coefficients of variation of indicators at all levels were 0 to 0.31 and 0 to 0.21, respectively. The final constructed evaluation index system for the quality of hospice care services included seven first level indicators, 22 second level indicators, and 42 third level indicators. Conclusions:The evaluation index system for the quality of hospice care services constructed is scientific, comprehensive, and targeted, which can provide reference for the comprehensive evaluation of hospice care service quality in China.

Objective To establish a scientific training program that takes into account both anaerobic and aerobic training for pilots,and to explore the appropriate ratio of aerobic and anaerobic training.Methods According to the physical examination standards for pilots,a total of 16 healthy subjects aged 18-24 were selected from two batches.The two batches of subjects were trained with different aerobic and anaerobic ratios.Training period was 3 months.The changes in cardiopulmonary function of the subjects before and after training were evaluated using the cardiopulmonary function exercise testing system(CPET),and the changes in anaerobic capacity were evaluated using changes in strength as an indicator.Results After training,the weight load of the subjects in the two training programs,including barbell squats,leg flexion and hard pull,and barbell under 10RM and 3RM,was significantly increased(P<0.001),and there was no statistically significant difference in anaerobic strength growth between the two groups.The results of CPET showed that the maximum load,maximum heart rate,and respiratory quotient in the two groups were significantly increased after than before the training(P<0.01).The maximum load(Experiment group 1:29.12±19.69,Experiment group 2:72.00±46.24)and respiratory quotient(Experiment grouop 1:0.11±0.09,Experiment group 2:0.28±0.16)of the subjects in experiment group 2 before and after training were greater than those in experiment group 1.The difference was statistically significant(P<0.05).Conclusion The anaerobic and aerobic capacities of the subjects in the experiment group 2 are effectively improved,indicating that ratio of aerobic and anaerobic of the training scheme is better.

Objective To investigate the effects and mechanisms of median nerve electrical stimulation on synaptic plasticity in ischemic stroke rats.Methods 18 healthy male SD rats were randomly divided into Sham group(n = 6),ischemic stroke group(MCAO group,n = 6)and median nerve electrical stimulation group(MNES group,n = 6).The left middle cerebral artery occlusion model of rats was established by thread plug method.Thread plug was not inserted in sham group.The median nerve electrical stimulation group was given median nerve electrical stimulation intervention on the 3rd day after modeling,and intervention on the next day.After intervention for 7 times,behavioral detection,HE staining was used to detect median nerve injury.Nissl staining was used to detect cerebral infarction volume.Western blot was used for detection of the expression level of proteins related to synaptic plasticity,and electron microscopy was performed.Results HE staining showed that median nerve electrical stimulation did not cause damage to the median nerve in stroke rats,and the median nerve membrane was intact without obvious inflammatory cells.Compared with MCAO group,the neural function,motor function and coordination of the injured forelimb in MNES group were significantly improved(P<0.01).Compared with MCAO group,cerebral infarction volume in MNES group was significantly reduced(P<0.05),the pyknosis of Nissl bodies in ischemic penumbra decreased.Compared with MCAO group,the expression levels of synaptic plastication-related proteins PSD95 and synI in the cortex of MNES group were significantly up-regulated after median nerve electrical stimulation(P<0.05),the number of synapses in the ischemic cortex increased significantly(P<0.01).Conclusion Median nerve electrical stimulation is a safe and effective therapeutic measure to improve nerve function after stroke,and its mechanism is related to promoting synaptic plasticity.

After ischemic stroke, the key to reduce the mortality and disability rate is to restore the blood supply of brain tissue as soon as possible. However, the cerebral ischemia-reperfusion injury (CIRI) caused by blood flow restoration is also an important cause of brain tissue structural damage and dysfunction. Studies in recent years have shown that the activation of mitophagy at CIRI stage can reduce the volume of cerebral infarction and protect neurons from CIRI, while excessive or insufficient mitophagy can aggravate CIRI. This suggests that inducing moderate mitophagy may be a potential therapeutic target for neuroprotection after stroke. However, the neuroprotective mechanism of mitophagy has not yet been fully elucidated. This article reviews the neuroprotective mechanism and potential application of mitophagy in stroke, and discusses some problems of mitophagy as a therapeutic target for stroke.

The continuing discoveries of novel classes of RNA modifications in various organisms have raised the need for improving sensitive, convenient, and reliable methods for quantifying RNA modifications. In particular, a subset of small RNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), are modified at their 3'-terminal nucleotides via 2'-O-methylation. However, quantifying the levels of these small RNAs is difficult because 2'-O-methylation at the RNA 3'-terminus inhibits the activity of polyadenylate polymerase and T4 RNA ligase. These two enzymes are indispensable for RNA labeling or ligation in conventional miRNA quantification assays. In this study, we profiled 3'-terminal 2'-O-methyl plant miRNAs in the livers of rice-fed mice by oxidative deep sequencing and detected increasing amounts of plant miRNAs with prolonged oxidation treatment. We further compared the efficiency of stem-loop and poly(A)-tailed RT-qPCR in quantifying plant miRNAs in animal tissues and identified stem-loop RT-qPCR as the only suitable approach. Likewise, stem-loop RT-qPCR was superior to poly(A)-tailed RT-qPCR in quantifying 3'-terminal 2'-O-methyl piRNAs in human seminal plasma. In summary, this study established a standard procedure for quantifying the levels of 3'-terminal 2'-O-methyl miRNAs in plants and piRNAs. Accurate measurement of the 3'-terminal 2'-O-methylation of small RNAs has profound implications for understanding their pathophysiologic roles in biological systems.
Animals ; High-Throughput Nucleotide Sequencing ; Humans ; Methylation ; Mice ; MicroRNAs/genetics* ; Oxidative Stress ; RNA, Small Interfering/metabolism* ; Real-Time Polymerase Chain Reaction

Objective:To analysis the status of the mental health and related factors of fire fighters in Tianjin Binhai New District, and to provide suggestions for their psychological health protection.Methods:399 fire fighters in Tianjin Binhai New District were selected as study subjects in Jan to April 2019. Depression symptoms were measured by the depression module of the Patient Health Questionnaire (PHQ-9) . The Chinese version of Efrort Reword Imbalance (ERI) Questionnnaire were used to investigate and evaluate their occupational stress. Chi-Square test was used to analysis Categorical data. Binary logistic regression model was used to analysis the ralated factors of depression.Results:Among the 399 fire fighters, 71.1% (280/394) were found high level of depression symptom. The detection rates of depression symptoms in the related influceing factors ERI、station、disease、life pressure、eating habits and sleep disorder occupational stress were difierent ( P<0.05) . Sleep disorder, life pressure and ERI occupational stress were risk factors for depressive symptoms ( OR=1.921, 95% CI=1.002-3.682; OR=2.852, 95% CI=1.561-5.212; OR=2.367, 95% CI=1.163-4.818, P<0.05) . Conclusion:The rate of depression of fire fighters is relatively higher. Government should pay attention to and take measures to improve the psychological condition of fire fighters.

Objective:To analysis the status of the mental health and related factors of fire fighters in Tianjin Binhai New District, and to provide suggestions for their psychological health protection.Methods:399 fire fighters in Tianjin Binhai New District were selected as study subjects in Jan to April 2019. Depression symptoms were measured by the depression module of the Patient Health Questionnaire (PHQ-9) . The Chinese version of Efrort Reword Imbalance (ERI) Questionnnaire were used to investigate and evaluate their occupational stress. Chi-Square test was used to analysis Categorical data. Binary logistic regression model was used to analysis the ralated factors of depression.Results:Among the 399 fire fighters, 71.1% (280/394) were found high level of depression symptom. The detection rates of depression symptoms in the related influceing factors ERI、station、disease、life pressure、eating habits and sleep disorder occupational stress were difierent ( P<0.05) . Sleep disorder, life pressure and ERI occupational stress were risk factors for depressive symptoms ( OR=1.921, 95% CI=1.002-3.682; OR=2.852, 95% CI=1.561-5.212; OR=2.367, 95% CI=1.163-4.818, P<0.05) . Conclusion:The rate of depression of fire fighters is relatively higher. Government should pay attention to and take measures to improve the psychological condition of fire fighters.

Colorectal cancer is one of the most common malignant tumors,early diagnosis and treatment are the important factors affecting colorectal cancer's prognosis.It has been proved that colorectal cancer's diagnosis combined with biomolecular markers is non-invasive,economical and specific at the same time,biomarkers are valuable in predicting and monitoring the chemoresistance of colorectal cancer.This article mainly reviews the prediction of liver metastasis of colorectal cancer,drug resistance of postoperative chemotherapy in colorectal cancer and the monitoring of drug resistance in the course of chemotherapy by CD44v6.

Protozoan viruses may influence the function and pathogenicity of the protozoa. Trichomonas vaginalis is a parasitic protozoan that could contain a double stranded RNA (dsRNA) virus, T. vaginalis virus (TVV). However, there are few reports on the properties of the virus. To further determine variations in protein expression of T. vaginalis, we detected 2 strains of T. vaginalis; the virus-infected (V⁺) and uninfected (V⁻) isolates to examine differentially expressed proteins upon TVV infection. Using a stable isotope N-terminal labeling strategy (iTRAQ) on soluble fractions to analyze proteomes, we identified 293 proteins, of which 50 were altered in V⁺ compared with V⁻ isolates. The results showed that the expression of 29 proteins was increased, and 21 proteins decreased in V⁺ isolates. These differentially expressed proteins can be classified into 4 categories: ribosomal proteins, metabolic enzymes, heat shock proteins, and putative uncharacterized proteins. Quantitative PCR was used to detect 4 metabolic processes proteins: glycogen phosphorylase, malate dehydrogenase, triosephosphate isomerase, and glucose-6-phosphate isomerase, which were differentially expressed in V⁺ and V⁻ isolates. Our findings suggest that mRNA levels of these genes were consistent with protein expression levels. This study was the first which analyzed protein expression variations upon TVV infection. These observations will provide a basis for future studies concerning the possible roles of these proteins in host-parasite interactions.
Glucose-6-Phosphate Isomerase ; Glycogen Phosphorylase ; Heat-Shock Proteins ; Host-Parasite Interactions ; Malate Dehydrogenase ; Metabolism ; Polymerase Chain Reaction ; Proteome ; Reticuloendotheliosis virus ; Ribosomal Proteins ; RNA, Double-Stranded ; RNA, Messenger ; Trichomonas vaginalis* ; Trichomonas* ; Triose-Phosphate Isomerase ; Virulence