Discovery of novel 2-aminopyridine derivatives as ROS1 and ALK dual inhibitors to combat drug-resistant mutants including ROS1G2032R and ALKG1202R.

Clinical treatment by FDA-approved ROS1/ALK inhibitor Crizotinib significantly improved the therapeutic outcomes. However, the emergence of drug resistance, especially driven by acquired mutations, have become an inevitable problem and worsened the clinical effects of Crizotinib. To combat drug resistance, some novel 2-aminopyridine derivatives were designed rationally based on molecular simulation, then synthesised and subjected to biological test. The preferred spiro derivative C01 exhibited remarkable activity against CD74-ROS1G2032R cell with an IC50 value of 42.3 nM, which was about 30-fold more potent than Crizotinib. Moreover, C01 also potently inhibited enzymatic activity against clinically Crizotinib-resistant ALKG1202R, harbouring a 10-fold potency superior to Crizotinib. Furthermore, molecular dynamic disclosed that introducing the spiro group could reduce the steric hindrance with bulky side chain (Arginine) in solvent region of ROS1G2032R, which explained the sensitivity of C01 to drug-resistant mutant. These results indicated a path forward for the generation of anti Crizotinib-resistant ROS1/ALK dual inhibitors.

Efficacy and confounding factors of CT attenuation value differences in distinguishing acute and old vertebral compression fractures: a retrospective study.

PURPOSE: To evaluate the influence of various factors on CT attenuation values (HUs) of acute and old fracture vertebra, and to determine the efficacy of HU differences (△HUs) in the differentiation of the two type of fractures. MATERIALS AND METHODS: A total of 113 acute and 71 old fracture vertebrae confirmed by MRI were included. Four HUs measured at the mid-sagittal, upper 1/3 axial, mid-axial, and lower 1/3 axial planes of each vertebra were obtained. The △HUs between fracture vertebra and its control counterpart was calculated. Receiver operating characteristic (ROC) curve analysis was used and the areas under the ROC curve (AUC) were calculated to evaluate the efficacy of HUs and △HUs. To evaluate the effect of height reduction, region, age and gender on HUs and △HUs, one-way analysis of variance, Pearson correlation analysis and t-test were used. RESULTS: The HUs and △HUs at the upper 1/3 axial plane achieved the highest AUCs of 0.801 and 0.839, respectively. The HUs decreased gradually from Thoracic to Lumbar in control group of acute fracture. While no significant differences were found in the HUs among the 3 localizations in both fracture groups (all P > 0.05). The HUs were negatively correlated with age in all groups. The HUs of male were significantly higher than female patients in all groups (all P < 0.05). While △HU was not significantly different between males and females (all P > 0.05). CONCLUSION: The vertebral HUs at the upper 1/3 axial plane are more likely to identify acute fractures. △HUs were beneficial in eliminating interfering factors.

MicroRNA-124-3p alleviates cerebral ischaemia-induced neuroaxonal damage by enhancing Nrep expression.

OBJECTIVE: Ischaemic stroke has a high death rate and frequently results in long-term and severe brain damage in survivors. miRNA-124-3p (miR-124-3p) treatment has been suggested to reduce ischaemia and play a vital function in avoiding neuron death. An investigation of the role of miR-124-3p, in the ischaemia damage repair or protection in the middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation/reperfusion (OGD/R) model, was the purpose of this research. METHODS: The expression of miRNA and mRNA in the MCAO model was predicted using bioinformatics analysis. The OGD/R neuronal model was developed. We examined the influence of a number of compounds on the OGD/R model in vitro using gain- and loss-of-function approaches. RESULTS: For starters, miR-124-3p and Nrep level in the MCAO model were found to be lower in the model predicted by bioinformatics than in the sham-operated group. And then in the OGD/R model, miR-124-3p treatment reduced OGD/R neuronal damage, increased neuronal survival, and reduced apoptosis in cell lines. Moreover, we further looked at the impact of miR-124-3p on downstream Rnf38 and Nrep using the OGD/R model. Western blot analysis and dual-luciferase reporter assays indicated that miR-124-3p binds and inhibits Rnf38. Finally, although Nrep expression was reduced in the OGD/R model neuronal model, it was shown that miR-124-3p administration reduced apoptosis and increased neuronal activity, particularly with regard to axon regeneration-related proteins. CONCLUSION: Our studies have shown that miR-124-3p may reduce neuronal injury by preventing Rnf38-mediated effects on the Nrep axis.

[Inquiry of Application Value about Medical Consumables Unique Device Identifier (UDI) in Internet of Things].

OBJECTIVE: To discuss how to implement and promote the lean management of medical devices life cycle through establishing medical device UDI. METHODS: Discuss the application of UDI on medical consumables lean management by relying on the construction of medical device UDI system in our country, and summarize the pilot experience of implanted medical devices in Shanghai. RESULTS: Improve the application value of UDI in medical device Internet of Things through analyzing the present situation of implanted medical device and further strengthen the UDI application standardization. CONCLUSIONS: Form the interconnection and mutual recognition during medical device life cycle and reduce the input of product cost and resource consumption in our country through establishing a more standardized and effective UDI circulation system.

Comparison of the Use of Magnetic Resonance Imaging of Partial Anterior Cruciate Ligament Tears Using Maximum Knee Flexion in the Lateral Decubitus Position with Routine Knee Positioning.

BACKGROUND This study assessed magnetic resonance imaging (MRI) of acute and chronic partial anterior cruciate ligament (ACL) tears using maximum knee flexion in the lateral decubitus position compared with routine knee positioning in 204 patients at a single center. MATERIAL AND METHODS Based on the time interval from injury to MRI examination, the 204 patients in this study were divided into 3 groups: subacute (6 weeks to 3 months), intermediate (3 months to 1 year), and chronic (>1 year). All patients received both routine MRI (MRI R) and maximum knee flexion in the lateral decubitus position MRI (MRI S) examination, followed by knee arthroscopy. Three radiologists blinded to patient groups evaluated the MRI scans and made a diagnosis. Results of knee arthroscopy were referenced as the criterion standard. The sensitivity and specificity of MRI R and MRI S groups were calculated and compared. RESULTS The MRI S diagnostic rate was comparable to that of knee arthroscopy. MRI S had significantly higher sensitivity than MRI R for partial ACL tears, especially in the intermediate group (P<0.01). CONCLUSIONS MRI of partial ACL tears using maximum knee flexion in the lateral decubitus position improved the diagnostic rate relative to routine MRI examination, particularly in patients in the intermediate group.

[Medical Consumable Management System Research under the New Situation].

With the continuous improvement of the difficulty of surgery, we need to investigate and analyze the current situation, to understand the structure and related attributes of medical consumables. Rely on the information construction of medical consumables; Improve the supervision method and further improve the refined management effect; Establish multi-modal procurement management; Improve management methods; Maximize the benefits of transformation structure and study the trace management of medical consumables in the key areas of the hospital's full life process at the same time. Provide data decision-making services for hospitals through the early warning management of medical consumables based on clinical quality management, and use tools such as HB-HTA to further construct a reasonable evaluation system for medical consumables.

[Discussion of Medical Protective Consumables Management to Fight against COVID-19 Pneumonia].

This article researches how to allocate medical protective consumables in hospital and ensure the safety of emergency marketing procurement under the condition that people are easily susceptible to COVID-19. To inform medical staffs about the standard instruction, we establish the corresponding hierarchical control management system and standards of medical protective consumables. To reduce the stress of clinical medical staff and prevent excessive protection, we enhance the training mechanisms and promote the superior normative guidance. The aim is to fully play the effectiveness of the key departments of medical protective consumables, reduce the risk of infection of clinical medical staff and ensure the safety of medical staffs.

[Clinical Pathway and Alert Management of Intelligent Medical Consumables].

Relying on the information construction of medical consumables, based on the use of single-disease medical consumables, establish a clinical pathway and early warning management of intelligent medical consumables to ensure the rational use of medical consumables. In this way, the supervision method is improved and the refined management effect is further improved. Establishing a clinical pathway and early warning management of intelligent medical consumables can more effectively standardize the rational use of medical consumables, and provide data monitor and control for economic evaluation in the management of single-disease in the future.

Activation of CaMKIIδA promotes Ca2+ leak from the sarcoplasmic reticulum in cardiomyocytes of chronic heart failure rats.

Activation of the Ca2+/calmodulin-dependent protein kinase II isoform δA (CaMKIIδA) disturbs intracellular Ca2+ homeostasis in cardiomyocytes during chronic heart failure (CHF). We hypothesized that upregulation of CaMKIIδA in cardiomyocytes might enhance Ca2+ leak from the sarcoplasmic reticulum (SR) via activation of phosphorylated ryanodine receptor type 2 (P-RyR2) and decrease Ca2+ uptake by inhibition of SR calcium ATPase 2a (SERCA2a). In this study, CHF was induced in rats by ligation of the left anterior descending coronary artery. We found that CHF caused an increase in the expression of CaMKIIδA and P-RyR2 in the left ventricle (LV). The role of CaMKIIδA in regulation of P-RyR2 was elucidated in cardiomyocytes isolated from neonatal rats in vitro. Hypoxia induced upregulation of CaMKIIδA and activation of P-RyR2 in the cardiomyocytes, which both were attenuated by knockdown of CaMKIIδA. Furthermore, we showed that knockdown of CaMKIIδA significantly decreased the Ca2+ leak from the SR elicited by hypoxia in the cardiomyocytes. In addition, CHF also induced a downregulation of SERCA2a in the LV of CHF rats. Knockdown of CaMKIIδA normalized hypoxia-induced downregulation of SERCA2a in cardiomyocytes in vitro. The results demonstrate that the inhibition of CaMKIIδA may improve cardiac function by preventing SR Ca2+ leak through downregulation of P-RyR2 and upregulation of SERCA2a expression in cardiomyocytes in CHF.

[Discussion about Management of In Vitro Diagnostic Reagent].

OBJECTIVE: In order to adapt the rapid development of modern medicine, this paper is aimed to analyze the application of in vitro diagnostic reagents (IVD Reagents) in hospital management and improve the overall level of hospital management. METHODS: By groping the management experience of IVD reagents, we discuss the internal hospital management mode of IVD reagents in reality. RESULTS: With the continuous improvements on the information platform of IVD reagents,we can realize benefit analysis of IVD reagents within the process of management. CONCLUSION: Reasonable management on IVD reagentscan improve the working efficiency in hospitals and provide swifter and better medical service for patients.

The effect of different exercise on physical fitness, cognition, and mental health in healthy older adults.

Objective: This study aimed to examine the effects of different exercise programs on physical fitness, cognition, and mental health in healthy older adults. Methods: A randomized controlled study was performed with 89 healthy older adults. They were separated into four groups: the control (Con; n = 20), physical activity (PA; n = 23), cognitive training (CT; n = 23), and physical activity coupled with cognitive training groups (PA + CT; n = 23). The subjects in PA, CT, and PA + CT groups received exercise programs that lasted 40 min daily, conducted at least three days a week for 20 weeks. The PA group received regular aerobic physical activity interventions, the CT group received cognitive training interventions, and the PA + CT group received physical activity combined with cognitive training interventions. Physical fitness (by chair stand, biceps curl, 2-min step, 8-step up and walk, and sit and reach tests), cognitive function (attention, simple reaction time, and spatial memory), and mental health (anxiety and depression status) were evaluated before and after 20 weeks. Results: The body composition results reveal no significant effects among the four groups after 20 weeks before and after aerobic exercise interventions (p > 0.05). Compared with Con, the PA, CT, and PA + CT groups significantly improved physical fitness parameters (p < 0.05). The post-hoc analysis demonstrated that the PA and PA + CT groups had higher fitness levels than the CT group. Similarly, a significant difference was observed in the cognitive index among the four groups (p < 0.05). As determined by post-hoc analysis, attention and simple reaction time differed sequentially between the Con, PA, CT, and PA + CT groups. The spatial memory was superior in the PA, CT, and PA + CT groups compared to the Con group (p < 0.05), with the PA + CT group exhibiting the highest level of performance. However, there was no significant difference in the mental health parameters among all the groups (p < 0.05). Conclusion: A 20-week intervention involving different exercise methods can enhance physical fitness, cognition, and mental health in older adults. These methods include physical activity, cognitive training, and a combination of physical and cognitive training. The combined physical activity and cognitive training interventions yielded more favorable outcomes than individual physical or cognitive training interventions.

Bibliometric analysis of the association between periodontal disease and cardiovascular disease.

Purpose: Conduct a bibliometric analysis to review the knowledge structure and research trends regarding the association between periodontal disease and cardiovascular disease (CVD). Methods: The Web of Science Core collection database was searched for retrieving publications related to periodontitis and CVD between January 1, 2003 and December 31, 2022. The VOSviewer, CiteSpace, and R software package "bibliometrix" were employed for the bibliometric analysis. Results: In total, 3447 articles were collected from 98 countries over the past 20 years, with the United States (1,003), Japan (377), and China (321) contributing the most publications. The literature in this field exhibited exponential growth. The University of Helsinki (n = 125, 1.37 %) holds the distinction of being the research institution with the highest number of publications, with a predominant representation from institutions in the United States. Notably, the Journal of Periodontology emerges as the most popular journal in the field, whereas the Journal of Clinical Periodontology takes the lead in terms of citations. These publications originated from 15,236 authors, with Pussinen (n = 40) having the highest number of published papers and Tonetti (n = 976) garnering the most citations. The visualization analysis of keywords identified "oral microbiome," "inflammation," and "porphyromonas gingivalis" as emerging research hotspots in exploring the relationship between periodontitis and CVDs. Conclusion: Through a comprehensive bibliometric analysis, this study posits that periodontitis may heighten the risk of cardiovascular events, offering valuable academic references for scholars investigating the link between periodontitis and CVDs.

Effect of physical exercise on postoperative shoulder mobility and upper limb function in patients with breast cancer: a systematic review and meta-analysis.

Background: The shoulder pain and reduced range of motion caused by breast cancer seriously affect the quality of life of women. Such persistent impairments can escalate into chronic pain, diminished muscle strength, lymphedema, and compromised cardiorespiratory health potentially culminating in permanent disability. This systematic review aims to evaluate how physical exercise impacts shoulder mobility and upper limb function in breast cancer patients post-surgery, examining various aspects of exercise such as type, intensity, duration, frequency, and intervention timing to determine the influence on outcomes. Methods: A comprehensive search was conducted across seven databases up to April 16, 2024. Two reviewers independently assessed randomized controlled trials (RCTs) focusing on the effects of physical exercise on postoperative outcomes in breast cancer patients. Quality was assessed using the Cochrane risk of bias tool, with meta-analyses and publication bias tests performed via RevMan5.4, and evidence quality evaluated using GRADEPro. Effect sizes were calculated using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results: Twenty studies (25 RCTs involving 2,171 patients) were included for both the systematic review and the meta-analysis. Meta-analysis confirmed that physical exercise significantly enhanced shoulder flexion (SMD =0.59; 95% CI: 0.32, 0.86; P<0.001) and abduction (SMD =1.01; 95% CI: 0.43, 1.60; P<0.001) in postoperative patients, and improved upper limb function (SMD =0.87; 95% CI: 0.48, 1.26; P<0.001). Subgroup analyses indicated that comprehensive exercise, particularly when performed ≤3 times a week or over 8-12 weeks, was most effective for improving shoulder flexion, while shorter durations (<8 weeks) and similar frequencies were optimal for abduction. Resistance exercises, especially when started early (<2 weeks post-surgery), showed significant benefits for upper limb function. Conclusions: The included studies were of moderate to high quality, though some lacked detailed reporting on blinding or allocation concealment. Analysis suggests that the timing of intervention initiation, along with exercise type and frequency, may contribute to observed variations in outcomes. Evidence quality assessments did not reveal significant issues with indirectness or imprecision, and no significant publication bias was detected. Given the low heterogeneity and absence of significant downgrade factors, intermediate evidence quality was assigned for upper limb function and shoulder abduction, with high quality for shoulder flexion. Physical exercise is notably effective in enhancing both upper limb function and shoulder mobility in breast cancer patients, with the timing and frequency of exercise interventions influencing these improvements. This provides valuable evidence for clinical rehabilitation strategies.

Core-Sheath Fiber-Based Triboelectric Nanogenerators for Energy Harvesting and Self-Powered Straight-Arm Sit-Up Sensing.

Fiber-based triboelectric nanogenerators (F-TENGs), a green and sustainable energy-harvesting and transformation technology, hold great potential in the areas of portable energy harvesters and smart wearable sensors. Herein, the core-sheath structure F-TENGs (CF-TENGs) are developed by using continuous production equipment. The CF-TENGs, consisting of an elastic conductive fiber (core layer) and silicone rubber (sheath layer), can simultaneously accomplish stable reversible strain and excellent electrical output performance. High outputs (an open-circuit voltage of 17.5 V and a short-circuit current of 0.1 µA at a frequency of 1 Hz) can be attained when the CF-TENGs (a length of 5 cm) are contacted with a nylon fabric. The CF-TENGs not only act as self-powered sensors for applications in motion monitoring but also efficiently transfer mechanical energy into electric energy. As self-powered wearable sensors, the CF-TENGs can accurately indicate various human physiological movements. Moreover, they can be applied on straight-arm sit-up sensing to achieve standardized sport testing. Importantly, a CF-TENG-based weaved fabric presents high electrical performance to meet requirements as an energy harvester. These CF-TENGs provide a significant insight to facilitate the development of fiber-based triboelectric applications.

Development trends and knowledge framework in the application of magnetic resonance imaging in prostate cancer: a bibliometric analysis from 1984 to 2022.

Background: Prostate cancer (PCa) is the most common tumor of the male genitourinary system. With the development of imaging technology, the role of magnetic resonance imaging (MRI) in the management of PCa is increasing. The present study summarizes research on the application of MRI in the field of PCa using bibliometric analysis and predicts future research hotspots. Methods: Articles regarding the application of MRI in PCa between January 1, 1984 and June 30, 2022 were selected from the Web of Science Core Collection (WoSCC) on November 6, 2022. Microsoft Excel 2016 and the Bibliometrix Biblioshiny R-package software were used for data analysis and bibliometric indicator extraction. CiteSpace (version 6.1.R3) was used to visualize literature feature clustering, including co-occurrence analysis of countries, institutions, authors, references, and burst keywords analysis. Results: A total of 10,230 articles were included in the study. Turkbey was the most prolific author. The USA was the most productive country and had strong partnerships with other countries. The most productive institution was Memorial Sloan Kettering Cancer Center. Journal of Magnetic Resonance Imaging and Radiology were the most productive and highest impact factor (IF) journals in the field, respectively. Timeline views showed that "#1 multiparametric magnetic resonance imaging", "#4 pi-rads", and "#8 psma" were currently the latest research hotspots. Keywords burst analysis showed that "machine learning", "psa density", "multi parametric mri", "deep learning", and "artificial intelligence" were the most frequently used keywords in the past 3 years. Conclusions: MRI has a wide range of applications in PCa. The USA is the leading country in this field, with a concentration of highly productive and high-level institutions. Meanwhile, it can be projected that "deep learning", "radiomics", and "artificial intelligence" will be research hotspots in the future.

Application of medical imaging in ovarian cancer: a bibliometric analysis from 2000 to 2022.

Background: Ovarian cancer (OC) is the most lethal tumor within the female reproductive system. Medical imaging plays a significant role in diagnosis and monitoring OC. This study aims to use bibliometric analysis to explore the current research hotspots and collaborative networks in the application of medical imaging in OC from 2000 to 2022. Methods: A systematica search for medical imaging in OC was conducted on the Web of Science Core Collection on August 9, 2023. All reviews and articles published from January 2000 to December 2022 were downloaded, and an analysis of countries, institutions, journals, keywords, and collaborative networks was perfomed using CiteSpace and VOSviewer. Results: A total of 5,958 publications were obtained, demonstrating a clear upward trend in annual publications over the study peroid. The USA led in productivity with 1,373 publications, and Harvard University emerged as the most prominent institution with 202 publications. Timmerman D was the most prolific contributor with 100 publications, and Gynecological Oncology led in the number of publications with 296. The top three keywords were "ovarian cancer" (1,256), "ultrasound" (725), and "diagnosis" (712). In addition, "pelvic masses" had the highest burst strength (25.5), followed by "magnetic resonance imaging (MRI)" (21.47). Recent emergent keywords such as "apoptosis", "nanoparticles", "features", "accuracy", and "human epididymal protein 4 (HE 4)" reflect research trends in this field and may become research hotspots in the future. Conclusion: This study provides a comprehensive summary of the key contributions of OC imaging to field's development over the past 23 years. Presently, primary areas of OC imaging research include MRI, targeted therapy of OC, novel biomarker (HE 4), and artificial intelligence. These areas are expected to influence future research endeavors in this field.

Correlation and pathways of behavioral activation systems mediating physical activity level and depressive symptoms among college students.

BACKGROUND: Depression is a common mental disorder among college students. The main symptoms include being persistent low mood, sad emotional experiences, lack of pleasure, listlessness, and impaired cognitive function accompanied by tendencies of self-harm and suicide. AIM: To clarify the pathways and effects of the behavioral activation system between physical activity and depressive symptoms in college students with depressive symptoms. METHODS: This cross-sectional research screened 3047 college students. Of these, 472 had depressive symptoms, with a depression detection rate of 15.49%. Furthermore, 442 college students with depressive symptoms were analyzed. A one-way analysis of variance and Pearson's correlation, linear regression, and structural equation modeling analyses were used to explore the correlations and pathways of the interactions between the variables. RESULTS: Depressive symptoms were significantly negatively correlated with physical activity (r = -0.175, P < 0.001), the behavioral activation system (r = -0.197, P < 0.001), and drive (r = -0.113, P = 0.017). Furthermore, it was negatively correlated with fun-seeking (FS) (r = -0.055, P = 0.251); however, it was not significant. Physical activity was significantly positively correlated with reward responsiveness (RR) (r = 0.141, P = 0.003) and drive (r = 0.124, P = 0.009) and not significantly positively correlated with FS (r = 0.090, P = 0.058). The mediating effect of RR between physical activity and depressive symptoms was significant [B = -0.025, 95% confidence interval (95%CI): -0.051 to -0.008, P = 0.001]. The direct and total effects of physical activity on depressive symptoms and were significant (B = -0.150, 95%CI: -0.233 to -0.073, P < 0.001; B = -0.175, 95%CI: -0.260 to -0.099, P < 0.001), respectively. CONCLUSION: As physical activity levels increased, depression scores among college students decreased. The mediating effect of RR between physical activity and depressive symptoms was significant. Therefore, colleges and universities should encourage college students with depression to increase their physical activity and improve their behavioral activation system. Particular attention should be paid to RR, which may reduce the prevalence of depressive symptoms.

The RNA m6A-Binding Protein YTHDC1 Is Downregulated and Associated With M2 Macrophage Infiltration in Muscle-Invasive Bladder Cancer.

Background: Dysregulation of RNA N6-methyladenosine (m6A) modification is indispensable in tumorigenesis. However, in muscle-invasive bladder cancer (MIBC), the key regulators and mechanisms involved in this process remain largely unknown. This study aimed to screen the key m6A regulators and explore its possible role in MIBC. Methods: Aberrantly expressed m6A regulator genes were screened in The Cancer Genome Atlas (TCGA) MIBC cohort (n = 408) and validated using fresh-frozen and formalin-fixed paraffin-embedded (FFPE) specimens collected during this study. Clinicopathological relevance and association with tumor immune infiltration was further assessed. Results: We identified that the expression of YT521-B homology-domain-containing protein 1 (YTHDC1), an m6A RNA-binding protein, was downregulated in tumor tissues compared with adjacent noncancerous tissues in the TCGA MIBC cohort and our clinical samples. Low YTHDC1 expression correlated with short patient survival, advanced pathologic stage, lymph node metastasis, basal-squamous molecular subtype, non-papillary histological type, and certain genetic mutations important to MIBC. Remarkably, YTHDC1 expression exhibited negative association with tumor-infiltrating M2 macrophage abundance in MIBC. Conclusion: Among m6A regulators, we identified that YTHDC1 was downregulated in MIBC and might play an important role in the pathological process in MIBC, especially tumor microenvironment regulation.

Both phthiocerol dimycocerosates and phenolic glycolipids are required for virulence of Mycobacterium marinum.

Phthiocerol dimycocerosates (PDIMs) and structurally related phenolic glycolipids (PGLs) are complex cell wall lipids unique to pathogenic mycobacteria. While these lipids have been extensively studied in recent years, there are conflicting reports on some aspects of their biosynthesis and on the role of PDIMs and especially PGLs in virulence of Mycobacterium tuberculosis. This has been complicated by the natural deficiency of PGLs in many clinical strains of M. tuberculosis and the frequent loss of PDIMs in laboratory M. tuberculosis strains. In this study, we isolated seven mutants of Mycobacterium marinum deficient in PDIMs and/or PGLs in which multiple genes of the PDIM/PGL biosynthetic locus were disrupted by transposon insertion. Zebrafish infection experiments showed that M. marinum strains lacking one or both of these lipids were avirulent, suggesting that both PDIMs and PGLs are required for virulence. We also found that these strains were hypersensitive to antibiotics and exhibited increased cell wall permeability. Our studies provide new insights into the biosynthesis of PDIMs/PGLs and may help us to understand the role of PDIMs and PGLs in M. tuberculosis virulence.

Ultrasonic scalpel combined with internal oxygen assisted sodium nitroprusside in laparoscopic cholecystectomy for elderly patients with acute cholecystitis.

To analyze the application value of an ultrasonic scalpel combined with internal oxygen assisted intravenous drip of sodium nitroprusside in laparoscopic cholecystectomy for elderly patients with acute cholecystitis. METHODS: A total of 76 patients with acute cholecystitis who were admitted to our hospital from January 2017 to December 2018 were included and equally divided into two groups. The control group was treated with ultrasonic scalpel alone, while the study group was treated with ultrasonic scalpel combined with internal oxygen and intravenous drip of sodium nitroprusside. The incidence of postoperative adverse reactions, the recovery of surgical indicators, the quality of life score before and after treatment, and the changes of serum sICAM-1 and IL-6 expression were observed. RESULTS: The incidence of postoperative adverse reactions in the study group was significantly higher than that in the control group (P < 0.05); and the recovery of surgical indicators in the study group was better than that in the control group (P < 0.05). After treatment, the levels of serum sICAM-1 and IL-6 in the two groups showed a certain degree of decline, and the levels of serum sICAM-1 and IL-6 inflammatory factors in the study group were significantly lower than those in the control group (P < 0.05). After treatment, the scores of psychological state, physical health, independent ability, social relationship, surrounding environment and personal belief of the two groups were significantly higher than those before treatment (P < 0.05). After treatment, the scores of each field in the treatment group were significantly higher than that in the control group (P < 0.05). CONCLUSION: It is safe and feasible to use an ultrasonic scalpel combined with internal oxygen to assist intravenous drip of sodium nitroprusside in the treatment of elderly patients with acute cholecystitis, but proper operation time and skilled operation are necessary.