Conditioned medium from human dental pulp stem cells treats spinal cord injury by inhibiting microglial pyroptosis

Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery after spinal cord injury remains unclear.In the present study,we established a rat model of spinal cord injury based on impact injury from a dropped weight and then intraperitoneally injected the rats with conditioned medium from human dental pulp stem cells.We found that the conditioned medium effectively promoted the recovery of sensory and motor functions in rats with spinal cord injury,decreased expression of the microglial pyroptosis markers NLRP3,GSDMD,caspase-1,and interleukin-1β,promoted axonal and myelin regeneration,and inhibited the formation of glial scars.In addition,in a lipopolysaccharide-induced BV2 microglia model,conditioned medium from human dental pulp stem cells protected cells from pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway.These results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway,thereby promoting the recovery of neurological function after spinal cord injury.Therefore,conditioned medium from human dental pulp stem cells may become an alternative therapy for spinal cord injury.

Distribution of gene polymorphisms associated with aspirin antiplatelet in the Han NSTEMI population

Objective:To analyze the genotype and allele distribution characteristics of GPⅢa PLA2(rs5918),PEAR1(rs12041331),and PTGS1(rs10306114)genes related to the antiplatelet pharmacological effects of aspirin,providing reference for individualized treatment of Chinese Han NSTEMI patients.Methods:A total of 107 Han patients with NSTEMI in Beijing Luhe Hospital affiliated to Capital Medical University from January 2016 to December 2022 were selected as the research subjects.The genotypes of GPⅢa PLA2(rs5918),PEAR1(rs12041331)and PTGS1(rs10306114)were detected by fluorescence staining in situ hybridization.The frequency distribution and allele distribution of genotype were analyzed.The results were analyzed whether there were statistical differences in the distribution of related alleles between the Han NSTEMI population and some populations in the 1000 Genomes database.Results:In the Han NSTEMI population,the genotype frequencies of GPⅢa PLA2(rs5918)locus were TT 97.20%,TC 2.80%and CC 0%,the allele frequencies were T 98.60%and C 1.40%.The genotype frequencies of PEAR1(rs12041331)locus were GG 42.06%,GA 44.86%and AA 13.08%,the allele frequencies were G 64.49%and A 35.51%.The genotypes at the PTGS1(rs10306114)locus were all AA(100%),no AG or GG genotype was found.Conclusion:In the NSTEMI population of Han nationality,the mutation at GPⅢa PLA2(rs5918)site related to aspirin antiplatelet pharmacology is rare,and there is no mutation at PTGS1(rs10306114)site.Wild homozygotes are dominant in these two gene loci,while mutations in PEAR1(rs12041331)are more common.Some of the findings in this study are similar to those in previous reports or other populations included in the relevant database;however,some results differ from previous reports or other populations。

Progress in immunotherapy for neuroendocrine neoplasm of the digestive system

Neuroendocrine neoplasms(NENs)are rare heterogeneous tumors that can develop in almost any organ,with the digestive organs,including the gastrointestinal tract and pancreas being the most commonly affected sites.Despite the fact that advances in initial therapies have progressed,there is presently no recognized effective treatment for advanced NEN.Immune checkpoint inhibitors(ICIs)have shown superior efficacy in treating several types of solid tumors.Despite their successful role in the treatment of partial NENs,such as small cell lung cancer,and Merkel cell carcinoma,the role of ICIs in most of the NENs remains limited.Nevertheless,due to their specific anti-tumor mechanisms and acceptable safety profile,ICIs are a promising avenue for further study in NENs therapy.Recent clinical trials have illustrated that combination therapy with ICI is more efficient than monotherapy,and multiple clinical trials are constantly ongoing to evaluate the efficacy and safety of these combination therapies.Therefore,the purpose of this review is to provide a comprehensive summary of the clinical progress of immunotherapy in NENs affecting the digestive system,with a specific emphasis on the application of programmed cell death protein 1/programmed death receptor ligand 1 inhibitor.Furthermore,this review has an exploration of the potential beneficiary population and the inherent value of utilizing immunotherapy in the management of NENs.

Evaluation of metoprolol standard dosing pathway in Chinese patients with acute coronary syndrome:a prospective multicenter single-arm interventional study

OBJECTIVE To evaluate the feasibility and tolerability of metoprolol standard dosing pathway(MSDP)in Chinese patients with acute coronary syndrome(ACS).METHODS In this multicenter,prospective,open label,single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals.A total of 998 hospitalized patients aged≥18 years and diagnosed with ACS were included.The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines.The primary endpoint was the percentage of patients achieving the target dose at discharge(V2).The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge(V4),and percentage of patients experiencing bradycardia(heart rate<50 beats/min),hypotension(blood pressure<90/60 mmHg)and transient cardiac dysfunction at V2 and V4.RESULTS Of the 998 patients,29.46%of patients achieved the target dose(≥95 mg/d)at V2.The total population was divided into two groups:target group(patients achieving the target dose at V2)and non-target group(patients not achieving the target dose at V2).There was significant difference in the reduction of heart rate from baseline to discharge in the two groups(-4.97±11.90beats/min vs.-2.70±9.47 beats/min,P=0.034).There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2(0 vs.0,P=1.000)and V4(0.81%vs.0.33%,P=0.715).There was no significant difference in the proportion of hypotension between the two groups at V2(0.004%vs.0.004%,P=1.000)and V4(0 vs.0.005%,P=0.560).No transient cardiac dysfunction occurred in two groups during the study.A total of five adverse events(1.70%)and one serious adverse event(0.34%)were related to the pathway in target group.CONCLUSIONS In Chinese ACS patients,the feasibility and tolerability of the MSDP have been proved to be acceptable.

Nicotinamide adenine dinucleotide phosphate oxidase activation and neuronal death after ischemic stroke

Nicotinamide adenine dinucleotide phosphate oxidase(NOX) is a multisubunit enzyme complex that utilizes nicotinamide adenine dinucleotide phosphate to produce superoxide anions and other reactive oxygen species. Under normal circumstances, reactive oxygen species mediate a number of important cellular functions, including the facilitation of adaptive immunity. In pathogenic circumstances, however,excess reactive oxygen species generated by NOX promotes apoptotic cell death. In ischemic stroke, in particular, it has been shown that both NOX activation and derangements in glucose metabolism result in increased apoptosis. Moreover, recent studies have established that glucose, as a NOX substrate, plays a vital role in the pathogenesis of reperfusion injury. Thus, NOX inhibition has the potential to mitigate the deleterious impact of hyperglycemia on stroke. In this paper, we provide an overview of this research,coupled with a discussion of its implications for the development of NOX inhibition as a strategy for the treatment of ischemic stroke. Both inhibition using apocynin, as well as the prospect of developing more specific inhibitors based on what is now understood of the biology of NOX assembly and activation, will be highlighted in the course of our discussion.

Surgical treatment ofpatients with severe non-flail chest rib fractures

BACKGROUND Many patients have inadequate long-term analgesia,respiratory distress,and hypoxemia due to a long-standing substantial smoking history or the presence of primary pulmonary diseases;analgesic treatment is not valid in these patients.Even if the imaging findings of rib fractures are relatively mild,rib fractures may cause severe position limitation,respiratory distress,and hypoxemia.AIM To investigate the curative effect of surgical treatment for patients with severe non-flail chest rib fractures.METHODS A total of 78 patients from our hospital with severe noncontinuous thoracic rib fractures from September 2016 to September 2018 were enrolled in our study.Thirty-nine patients underwent surgical treatment,and 39 underwent conservative treatment.The surgical treatment group received surgery performed with titanium plates,and the screws were inserted with open reduction and internal fixation.The conservative treatment group received analgesia and symptomatic treatment.The pain scores at 72 h,1 wk,2 wk,4 wk,6 wk,3 mo,and 6 mo were compared,and the SF-36 quality of life scores were compared atthe 3rd and 6th months.RESULTS Pain relief in the surgical group was significantly better than that in the conservative group at each time point(72 h,1 wk,2 wk,4 wk,6 wk,3 mo,and 6 mo after surgery,P<0.001).The SF-36 scores were significantly higher in the surgical group than in the conservative group at 1 mo and 6 mo(P<0.05).CONCLUSION Patients with severe non-flail chest rib fractures have a better quality of life following surgical treatment than following conservative treatment,and surgical treatment is also useful for relieving pain.We should pay more attention to the physiological functions and clinical manifestations of patients with severe rib fractures.In patients with non-flail chest rib fractures,surgical treatment is feasible and effective.

Sequential treatment of severe pneumonia with respiratory failure and its influence on respiratory mechanical parameters and hemodynamics

BACKGROUND The pathophysiological characteristics of severe pneumonia complicated by respiratory failure comprise pulmonary parenchymal changes leading to ventilation imbalance,alveolar capillary injury,pulmonary edema,refractory hypoxemia,and reduced lung compliance.Prolonged hypoxia can cause acid-base balance disorder,peripheral circulatory failure,blood-pressure reduction,arrhythmia,and other adverse consequences.AIM To investigate sequential mechanical ventilation’s effect on severe pneumonia complicated by respiratory failure.METHODS We selected 108 patients with severe pneumonia complicated by respiratory failure who underwent mechanical ventilation between January 2018 and September 2020 at the Luhe Hospital’s Intensive Care Unit and divided them into sequential and regular groups according to a randomized trial,with each group comprising 54 patients.The sequential group received invasive and non-invasive sequential mechanical ventilation,whereas the regular group received invasive mechanical ventilation.Blood-gas parameters,hemodynamic parameters,respiratory mechanical parameters,inflammatory factors,and treatment outcomes were compared between the two groups before and after mechanical-ventilation treatment.RESULTS The arterial oxygen partial pressure and stroke volume variation values of the sequential group at 24,48,and 72 h of treatment were higher than those of the conventional group(P<0.05).The carbon dioxide partial pressure value of the sequential group at 72 h of treatment and the Raw value of the treatment group at 24 and 48 h were lower than those of the conventional group(P<0.05).The pH value of the sequential group at 24 and 72 h of treatment,the central venous pressure value of the treatment at 24 h,and the Cst value of the treatment at 24 and 48 h were higher than those of the conventional group(P<0.05).The tidal volume in the sequential group at 24 h of treatment was higher than that in the conventional group(P<0.05),the measured values of interleukin-6 and tumor necrosis factor-αin the sequential group at 72 h of treatment were lower than those in the conventional group(P<0.05),and the total time of mechanical ventilation in the sequential group was shorter than that in the conventional group,with a statistically significant difference(P<0.05).CONCLUSION Treating severe pneumonia complicated by respiratory failure with sequential mechanical ventilation is more effective in improving respiratory system compliance,reducing inflammatory response,maintaining hemodynamic stability,and improving patient blood-gas levels;however,from this study’s perspective,it cannot reduce patient mortality.

Characteristics and clinical outcome of nonsteroidal anti-inflammatory drug-induced acute hepato-nephrotoxicity among Chinese patients

AIM:To determine the clinicopathological characteristics of nonsteroidal anti-inflammatory drug(NSAID)-induced acute hepato-nephrotoxicity among Chinese patients.METHODS:We conducted a retrospective chart review of patients using the International Classification of Diseases,Ninth Revision diagnosis code for acute kidney injury(AKI)(584.5 or 584.9)and for acute liver injury(ALI)(570.0 or 573.3)from January 2004 to December 2013.Medical records were reviewed to confirm the diagnosis of AKI and ALI and to quantify NSAID administration.RESULTS:Seven of 59 patients(11.8%)were identified with acute hepato-nephrotoxicity induced by NSAIDs.Five patients(71.4%)received over the recommended NSAIDs dose.Compared with NSAIDsassociated mere AKI,the risk factors of NSAIDsinduced acute hepato-nephrotoxicity are age older than 60 years(57.1%),a high prevalence of alcohol use(71.4%)and positive hepatitis B virus(HBV)markers(85.7%).Compared with NSAIDs-associated mere ALI,the risk factors of NSAIDs-induced acute hepatonephrotoxicity are age older than 60 years(57.1%),increased extracellular volume depletion(71.4%),and renin-angiotensin-aldosterone system(RAAS)inhibitor combined use(57.1%).Acute interstitial nephritis and acute tubulointerstitial disease were apparent in three out of six(42.9%)kidney biopsy patients,respectively.Acute hepatitis was found in four out of six(66.7%)liver biopsy patients.Overall complete recovery occurred in four patients within a mean of 118.25±55.42 d.CONCLUSION:The injury typically occurred after an overdose of NSAIDs.The risk factors include age older than 60 years,alcohol use,positive HBV markers,extracellular volume depletion and RAAS inhibitor combined use.

A retrospective analysis of the safety and efficacy of apatinib in treating advanced metastatic colorectal cancer

Objective Colorectal cancer(CRC) is a heterogeneous disease in which both epigenetic alterations and gene mutations transform normal cells into cancer cells. Apart from a variety of standard treatments, there are few options available to improve a CRC patient's overall survival(OS) and quality of a life. The objective of the present retrospective study was to analyze the response and toxicity associated with apatinib in patients with metastatic CRC(m CRC).Method Data on the use of apatinib as salvage therapy were collected from patients diagnosed with m CRC, Eastern Cooperative Oncology Group(ECOG) performance status ≤ 3, from the Luhe Hospital. A total of 17 patients with stage IV unresectable m CRC, who received at least one cycle of apatinib, between October 2015 and February 2017, were involved in this study. Our primary endpoints were the overall response rate(ORR) and disease control rate(DCR), and the secondary objectives were progression-free survival(PFS), OS and safety.Result Seventeen patients with a median age of 62 years(34–83 years) were enrolled. Twelve patients were male, and the location of the primary tumor was in the colon and the rectum in 9 and 8 patients, respectively. Liver metastasis was observed in 9 patients and lung metastasis in 5. The ECOG performance status was 0 to 2 in 13 patients. The ORR at the first evaluation was 17.6 %(3/17). The DCR was 82.4%(14/17). The median PFS was 3.0 months(95% confidence interval(CI): 1.924–4.076 months) and the median OS was 5.4 months(95% CI: 3.383–7.417 months). Grade 1–2 adverse events included hypertension(52.9%), fatigue(64.7%), anorexia(29.4%), hoarseness(23.5%), proteinuria(23.5%), and development of rashes(17.6%). Grade 3 adverse events included thrombocytopenia(5.9%) and proteinuria(5.9%). There were no Grade 4 adverse events in our analysis.Conclusions Apatinib was found to be both safe and effective in the treatment of advanced m CRC, and its associated toxicities were acceptable and manageable. However, further studies are required to validate these findings.

Melatonin for the treatment of spinal cord injury

Spinal cord injury（SCI） from trauma or disease severely impairs sensory and motor function. Neurorehabilitation after SCI is a complex medical process that focuses on improving neurologic function and repairing damaged connections in the central nervous system. An increasing number of preclinical studies suggest that melatonin may be useful for the treatment of SCI. Melatonin is an indolamine that is primarily secreted by the pineal gland and known to be regulated by photoperiodicity. However, it is also a versatile hormone with antioxidative, antiapoptotic, neuroprotective, and anti-inflammatory properties. Here, we review the neuroprotective properties of melatonin and the potential mechanisms by which it might be beneficial in the treatment of SCI. We also describe therapies that combine melatonin with exercise, oxytetracycline, and dexamethasone to attenuate the secondary injury after SCI and limit potential side effects. Finally, we discuss how injury at different spinal levels may differentially affect the secretion of melatonin.

Advancements in our understanding of circular and long non-coding RNAs in spinal cord injury

Spinal cord injury(SCI),either from trauma or degenerative changes,can res ult in severe disability and impaired quality of life.Understanding the cellular processes and molecular mechanisms that underlie SCI is imperative to identifying molecular targets for potential therapy.Recent studies have shown that non-coding RNAs,including both long non-coding RNAs(lncRNAs)and circular RNAs(circRNAs),regulate various cellular processes in SCI.In this review,we will describe the changes in lncRNA and circRNA expression that occur after SCI and how these changes may be related to SCI progression.Current evidence for the roles of lncRNAs and circRNAs in neuronal cell death and glial cell activation will also be reviewed.Finally,the possibility that lncRNAs and circRNAs are novel modulato rs of SCI pathogenesis will be discussed.

Hepatitis B virus reactivation in rheumatoid arthritis

Rheumatoid arthritis(RA)is an autoimmune disease characterized by proliferative synovitis,which can cause cartilage and bone damage as well as functional limitations.Disease-modifying anti-rheumatic drugs have significantly improved the prognosis of RA patients.However,people with RA,when combined with hepatitis B virus(HBV)infection,may experience reactivation of HBV during treatment with anti-rheumatic drugs.The outcome of HBV reactivation(HBVr)varies from liver inflammation to liver failure,while insufficient HBV screening in RA patients has been reported in various countries.Therefore,it is necessary to identify patients at high risk before starting immunosuppressive therapy.The immune response plays an important role in anti-HBV infection.However,most anti-rheumatic drugs exert an inhibitory effect on the body’s immune system,resulting in HBVr.Therefore,it is necessary to conduct a comprehensive evaluation based on host factors,viral factors,and drug factors.In this paper,we summarize the mechanism of HBVr,the risk of HBVr caused by anti-rheumatic drugs,and the appropriate diagnosis and treatment process for RA patients so that clinicians can have a more comprehensive understanding of HBVr in RA patients.

Effects of oral cetirizine combined with budesonide inhalation on immune inflammatory response in children with acute asthma attack

Objective: To study the effects of oral cetirizine combined with budesonide inhalation on immune inflammatory response in children with acute asthma attack. Methods: Children with acute asthma attack who were treated in Beijing Luhe Hospital Affiliated to Capital Medical University between April 2014 and February 2017 were selected and randomly divided into two groups, observation group received oral cetirizine combined with budesonide inhalation therapy, and control group received budesonide inhalation therapy. The contents of CD4+T cell subsets and the expression of immune transcription factors in peripheral blood as well as the contents of CD4+T cytokines and inflammatory mediators in serum were measured after 1 week of treatment. Results: After 1 week of treatment, Th1 and Treg contents as well as BCL11B, STAT4 and SOCS3 mRNA expression in peripheral blood as well as IFN-γand IL-10 contents in serum of observation group were greatly higher than those of control group while Th2, Th17 and Th22 contents as well as STAT1 and STAT3 mRNA expression in peripheral blood as well as IL-4, IL-17, IL-22, HMGB1, Periostin, Eotaxin and ADAM33 contents in serum were greatly lower than those of control group. Conclusion: Oral cetirizine combined with budesonide inhalation is more effective than budesonide inhalation alone to modulate the immune inflammatory response in children with acute asthma attack.

Preventive online and offline health management intervention in polycystic ovary syndrome

BACKGROUND Polycystic ovary syndrome(PCOS) is characterized by hyperandrogenism, hyperinsulinemia, ovarian polycystic changes, and irregular ovulation, often occurring in women of childbearing age for whom it can be a cause of infertility. Hypothalamus-pituitary-ovarian axis dysregulation is important in the pathogenesis of PCOS and the associated chronic excess of sex hormones can lead to cardiovascular and cerebrovascular diseases, diabetes, and malignancies such as endometrial cancer, and breast cancer. At present, most scholars agree that lifestyle interventions in conjunction with drug treatment can help PCOS patients achieve their goals of successful pregnancy and childbirth.AIM To investigate the clinical effect of an online and offline(O2O) preventive health management model on PCOS with kidney deficiency and phlegm dampness.METHODS A total of 82 patients with PCOS of the kidney deficiency and phlegm dampness type who were admitted to Beijing Luhe Hospital Affiliated to Capital Medical University from April 2019 to June 2020 were randomly divided into two groups. The treatment group was treated with oral Diane-35 for 3 mo and received preventive O2O medical health management for 6 mo(including eating and living, exercise, drug management). The control group was treated with oral Diane-35 for 3 mo and completed outpatient health education. The traditional Chinese medicine(TCM) syndrome score, acne score, hair score, sex hormone level and clinical effects were compared between the two groups before and after the intervention. RESULTS After treatment, the TCM syndrome score, acne score, and serum luteinizing hormone/follicle stimulating hormone level were significantly lower in the treatment group than in the control group(P < 0.05). After 3 mo of treatment, the TCM syndrome curative effect index in the treatment group was 97.30% compared to 54.05% in the control group(P < 0.05), whereas the total treatment effect in the treatment group was 91.89%, compared to 54.05% in the control group(P < 0.05).CONCLUSION An integrated therapeutic approach incorporating medication, TCM methods and social media is more effective than standard treatment for PCOS.

Bladder perforation injury after percutaneous peritoneal dialysis catheterization:A case report

BACKGROUND Insertion of a catheter into the bladder is a rare complication of peritoneal dialysis(PD),and is mainly related to surgical injury.This paper reports a case of bladder perforation that was caused by percutaneous PD catheterization.CASE SUMMARY A 64-year-old man underwent percutaneous PD catheterization for end-stage renal disease.On the second day after the operation,urgent urination and gross hematuria occurred.Urinalysis showed the presence of red and white blood cells.Empirical anti-infective treatment was given.On the third day after the operation,urgent urination occurred during PD perfusion.Ultrasound showed that the PD catheter was located in the bladder,and subsequent computed tomography(CT)showed that the PD catheter moved through the anterior wall into the bladder.The PD catheter was withdrawn from the bladder and catheterization was retained.Repeat CT on the fourth day after the operation showed that the PD catheter was removed from the bladder,but there was poor catheter function.The PD catheter was removed and the patient was changed to hemodialysis.CT cystography showed that the bladder healed well and the patient was discharged 14 d after the operation.CONCLUSION Bladder perforation injury should be considered and treated timeously in case of bladder irritation during and after percutaneous PD catheterization.The use of Doppler ultrasound and other related technologies may reduce the incidence of such complications.

Current AQP research:therapeutic approaches to ischemic and hemorrhagic stroke

The role of aquaporins（AQPs）in the formation of cerebral edema after stroke：Stroke can be classified into either ischemic or hemorrhagic based on their etiological mechanism.Cerebral edema development often accompanies both ischemic infarct and intracerebral hemorrhage（ICH）.Cerebral edema is differentiated according to their underlying mechanism and time course：cytotoxic and vasogenic.

Mechanisms of bone pain:Progress in research from bench to bedside

The field of research on pain originating from various bone diseases is expanding rapidly, with new mechanisms and targets asserting both peripheral and central sites of action. The scope of research is broadening from bone biology to neuroscience,neuroendocrinology, and immunology. In particular, the roles of primary sensory neurons and non-neuronal cells in the peripheral tissues as important targets for bone pain treatment are under extensive investigation in both pre-clinical and clinical settings. An understanding of the peripheral mechanisms underlying pain conditions associated with various bone diseases will aid in the appropriate application and development of optimal strategies for not only managing bone pain symptoms but also improving bone repairing and remodeling, which potentially cures the underlying etiology for long-term functional recovery. In this review, we focus on advances in important preclinical studies of significant bone pain conditions in the past 5 years that indicated new peripheral neuronal and non-neuronal mechanisms, novel targets for potential clinical interventions, and future directions of research.

Human Serum-derived Extracellular Vesicles Protect A549 from PM_(2.5)-induced Cell Apoptosis

Objective Epidemiological studies reveal that exposure to fine particulate matter(aerodynamic diameter≤2.5μm,PM_(2.5))increases the morbidity and mortality of respiratory diseases.Emerging evidence suggests that human circulating extracellular vesicles(EVs)may offer protective effects against injury caused by particulate matter.Currently,however,whether EVs attenuate PM_(2.5)-induced A549 cell apoptosis is unknown.Methods EVs were isolated from the serum of healthy subjects,quantified via nanoparticle tracking analysis,and qualified by the marker protein CD63.PM_(2.5)-exposed(50μg/mL)A549 cells were pretreated with 10μg/mL EVs for 24 h.Cell viability,cell apoptosis,and AKT activation were assessed via Cell Counting Kit-8,flow cytometry,and Western blot,respectively.A rescue experiment was also performed using MK2206,an AKT inhibitor.Results PM_(2.5)exposure caused a 100%in crease in cell apoptosis.EVs treatme nt reduced cell apoptosis by 10%,promoted cell survival,and inhibited the PM_(2.5)-induced upregulation of Bax/Bcl2 and cleaved caspase 3/caspase 3 in PM_(2.5)-exposed A549 cells.Moreover,EVs treatment reversed PM_(2.5)-induced reductions in p-AKT^(Thr308)and p-AKT^(Ser473).A KT inhibition attenuated the anti-apoptotic effect of EVs treatment on PM_(2.5)-exposed A549 cells.Conclusions EVs treatment promotes cell survival and attenuates PM_(2.5)-induced cell apoptosis via AKT phosphorylation.Human serum-derived EVs may be an efficacious novel therapeutic strategy in PM_(2.5)-induced lung injury.

Real world effectiveness of PCSK-9 inhibitors combined with statins versus statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease in China(RWE-PCSK study)

BACKGROUND The efficacy and safety of proprotein convertase subtilisin/kexin type 9(PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease(ASCVD).METHODS This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention(PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events(MACE) over six months were compared between two groups.A propensity score-matched(PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE.RESULTS In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol(LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81%(P < 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group(P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE(hazard ratio = 2.52, 95% CI: 0.49-12.97, P = 0.250).CONCLUSIONS In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study.

Scapular bone grafting with allograft pin fixation for repair of bony Bankart lesions: A biomechanical study

BACKGROUND Severe bony Bankart lesions are a difficult challenge in clinical treatment and research.The current treatment methods consist mostly of Latarjet-Bristow surgery and its modified procedures.While good results have been achieved,there are also complications such as coracoid fracture,bone graft displacement,and vascular and nerve injury.AIM To analyze the techniques and biomechanical properties of transversely fixing a bone block from the scapular spine using bone allograft pins with suture threads to repair bony Bankart lesions.METHODS Fresh human shoulder joint specimens and a cadaver specimen model for scapular bone grafting with allograft pin fixation for repair of bony Bankart lesions were used.When the humeral rotation angles were 0°,30°,60°and 90°,and the axial loads were 30 N,40 N,and 50 N,the humerus displacement was studied by biomechanical experiments.RESULTS When the angle of external rotation of the humerus was 0°,30°,60°,and 90°,with axial loads of 30 N,40 N,and 50 N,the data of the normal control group,allograft pin repair group,and titanium alloy hollow screw repair group were compared with each other by the q-test,which showed that there were no statistically differences among the three groups(P>0.05).CONCLUSION The joints repaired with bone block from the scapular spine transversely fixed with allograft bony pins to repair bony Bankart lesions show good mechanical stability.The bone block has similar properties to normal glenohumeral joints in terms of biomechanical stability.