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 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.

BACKGROUND:Acromion morphology is the most important external factor of degenerative rotator cuff tear,and studies on acromion morphology and acromion coverage have been continuing. OBJECTIVE:To investigate the coverage of acromion on rotator cuff tissue in three-dimensional space,measure coronal and sagittal parameters,and explore the relationship of acromial overhang,acromioglenoid angle and acromial coverage angle with degenerative full-thickness rotator cuff tears. METHODS:A total of 56 patients diagnosed with full-thickness rotator cuff tears by shoulder arthroscopic surgery or MRI in the Affiliated Hospital of Xuzhou Medical University from January 2022 to June 2023 were retrospectively collected as the tear group,while 48 patients with non-rotator cuff tear were included as the control group.Clinical data and chest CT data of the patients of the two groups were collected,and the shoulder blades of the patients were reconstructed using Mimics software.Acromial overhang,acromioglenoid angle and acromial coverage angle were measured in 3-matic software.The differences between the measurement parameters were compared between the two groups.Binary Logistic regression analysis and receiver operating characteristic curve analysis were performed to evaluate the ability of the measurement parameters to predict rotator cuff tear.It is generally believed that the parameter had good diagnostic value when the area under the receiver operating characteristic curve was greater than 0.8. RESULTS AND CONCLUSION:(1)The mean acromial overhang in patients with rotator cuff tears was greater than that in controls(P<0.001).The mean acromial coverage angle was also greater in patients with rotator cuff tears than in controls(P<0.001).There was no significant difference in the acromioglenoid angle between the two groups(P>0.05).(2)Binary Logistic regression analysis showed that acromial overhang and acromial coverage angle were both risk factors for rotator cuff tear(P<0.05).(3)Receiver operating characteristic curve analysis indicated that the areas under the curve of acromial overhang and acromial coverage angle were 0.725 and 0.865,respectively,and the optimal cutoff values were 36.15 mm and 60.65°.(4)The results showed that the acromial overhang and acromial coverage angle were greater in patients with rotator cuff tears than in patients without rotator cuff tears.Both were associated with degenerative full-thickness rotator cuff tears,and they could be used to predict rotator cuff tears,and the acromial coverage angle was more effective in predicting rotator cuff tears.

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.

Objective:To investigate the alteration of right ventricular function after catheter ablation in patients with persistent atrial fibrillation(PAF) and concomitant heart failure with preserved ejection fraction (HFpEF).Methods:The prospective observational study was performed in patients with HFpEF-PAF and undergoing first-time radiofrequency ablation procedures in the First Affiliated Hospital of Nanjing University between May to December 2019. Right ventricular functional parameters were measured before and 5 days, 1, 3, 6 and 12 months after the ablation by transthoracic echocardiography, respectively, including the right ventricular fractional area change (RVFAC), tricuspid annular plane systolic excursion(TAPSE), tricuspid annular diameter (TVAD), tricuspid annular peak systolic speed(TDI-S′) and longitudinal strain of right ventricular free wall (RVFLS). Meanwhile, routine ECG and Holter recordings were performed at each follow-up time point.Results:In this study, atrial fibrillation (AF) recurrence occurred in 4 patients at the 3rd month after ablation, and 7 patients failed to follow up due to the Covid-19. Finally, 19 patients were followed up for the evaluation of cardiac function after catheter ablation. Compared with pre-ablation, right ventricular structural and functional paramters(RVFAC, TAPSE, TVAD, TDI-S′, RVFLS) improved significantly at all stages of follow-up( all P<0.05). Patients with atrial fibrillation recurrence had lower RVFLS and TDI-S′ at the baseline( P=0.039, P=0.019). Conclusions:Right ventricular function could improve in HFpEF-PAF patients who maintain sinus rhythm after radiofrequency ablation.

This study introduces a non-invasive gastrointestinal early cancer magnetic anchor ablation electrode endoscopy system, including a magnetic anchor module and ablation electrode module. The magnetic anchoring module is composed of an external guide magnet and an internal magnet, made of permanent magnet material NdFeB; the ablation electrode module is based on the modification of the front end lens hood of the existing endoscope (CMD-90D LED electronic upper gastrointestinal endoscope). The new endoscope system not only includes all the functions of the original endoscope, but also introduces magnetic anchoring to enable the ablation electrode to be accurately positioned and controllable in the process of treating tumors, avoiding the phenomenon of gastric perforation; the introduction of steep pulse electric field ablation electrodes realizes the purpose of non-invasive treatment. Its clinical application will become a new method to treat early cancer of the digestive tract.
Electrodes ; Endoscopes ; Gastrointestinal Tract ; Humans ; Magnetic Phenomena ; Neoplasms

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.

With the development of magnetic materials more widely used in surgical instruments, the development of magnetic surgery technology has continuously made breakthroughs and innovations. Magnetic anchor assist technology has become an important surgical method due to its precise positioning and non-contact traction. The majority of clinical magnetic anchor system consist a target magnet in vivo and a traction magnet in vitro. The non-contact traction and anchoring of the target can be achieved through the mechanical interaction of the anchor magnet and the traction magnet. This method not only can prevent the entanglement and collision between surgical instruments, but also can provide a good surgical field of vision for the surgical area, making the surgical process safer and more efficient. In this paper, 69 articles related to the application of magnetic anchor assist technology in surgical procedures were retrieved by conducting searches in the Chinese Journal Full-text Database(CNKI), Wanfang Database, VIP Chinese Sci-tech Journal Database, PubMed and other databases. After analysis and evaluation, a total of 36 papers were screened. The research progress and application status of magnetic anchor assist technology in combination with laparoscopy, thoracoscopy, and endoscopy in surgical operations were introduced. The results show that the magnetic anchor assist technology can greatly promote the development of minimally invasive surgery, but there are still problems in the application process, such as mutual interference of magnets and instability of the magnetic force, which still need to be further studied and improved.

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.