ObjectivePhotoacoustic pump-probe imaging can effectively eliminate the interference of blood background signal in traditional photoacoustic imaging, and realize the imaging of weak phosphorescence molecules and their triplet lifetimes in deep tissues. However, background differential noise in photoacoustic pump-probe imaging often leads to large fitting results of phosphorescent molecule concentration and triplet lifetime. Therefore, this paper proposes a novel triplet lifetime fitting method for photoacoustic pump-probe imaging. By extracting the phase of the triplet differential signal and the background noise, the fitting bias caused by the background noise can be effectively corrected. MethodsThe advantages and feasibility of the proposed algorithm are verified by numerical simulation, phantom and in vivo experiments, respectively. ResultsIn the numerical simulation, under the condition of noise intensity being 10% of the signal amplitude, the new method can optimize the fitting deviation from 48.5% to about 5%, and has a higher exclusion coefficient (0.88>0.79), which greatly improves the fitting accuracy. The high specificity imaging ability of photoacoustic pump imaging for phosphorescent molecules has been demonstrated by phantom experiments. In vivo experiments have verified the feasibility of the new fitting method proposed in this paper for fitting phosphoometric lifetime to monitor oxygen partial pressure content during photodynamic therapy of tumors in nude mice. ConclusionThis work will play an important role in promoting the application of photoacoustic pump-probe imaging in biomedicine.

Obstructive sleep apnea (OSA) is an increasingly widespread sleep-breathing disordered disease, and is an independent risk factor for many high-risk chronic diseases such as hypertension, coronary heart disease, stroke, arrhythmias and diabetes, which is potentially fatal. The key to the prevention and treatment of OSA is early diagnosis and treatment, so the assessment and diagnostic technologies of OSA have become a research hotspot. This paper reviews the research progresses of severity assessment parameters and diagnostic technologies of OSA, and discusses their future development trends. In terms of severity assessment parameters of OSA, apnea hypopnea index (AHI), as the gold standard, together with the percentage of duration of apnea hypopnea (AH%), lowest oxygen saturation (LSpO₂), heart rate variability (HRV), oxygen desaturation index (ODI) and the emerging biomarkers, constitute a multi-dimensional evaluation system. Specifically, the AHI, which measures the frequency of sleep respiratory events per hour, does not fully reflect the patients’ overall sleep quality or the extent of their daytime functional impairments. To address this limitation, the AH%, which measures the proportion of the entire sleep cycle affected by apneas and hypopneas, deepens our understanding of the impact on sleep quality. The LSpO₂ plays a critical role in highlighting the potential severe hypoxic episodes during sleep, while the HRV offers a different perspective by analyzing the fluctuations in heart rate thereby revealing the activity of the autonomic nervous system. The ODI provides a direct and objective measure of patients’ nocturnal oxygenation stability by calculating the number of desaturation events per hour, and the biomarkers offers novel insights into the diagnosis and management of OSA, and fosters the development of more precise and tailored OSA therapeutic strategies. In terms of diagnostic techniques of OSA, the standardized questionnaire and Epworth sleepiness scale (ESS) is a simple and effective method for preliminary screening of OSA, and the polysomnography (PSG) which is based on recording multiple physiological signals stands for gold standard, but it has limitations of complex operations, high costs and inconvenience. As a convenient alternative, the home sleep apnea testing (HSAT) allows patients to monitor their sleep with simplified equipment in the comfort of their own homes, and the cardiopulmonary coupling (CPC) offers a minimal version that simply analyzes the electrocardiogram (ECG) signals. As an emerging diagnostic technology of OSA, machine learning (ML) and artificial intelligence (AI) adeptly pinpoint respiratory incidents and expose delicate physiological changes, thus casting new light on the diagnostic approach to OSA. In addition, imaging examination utilizes detailed visual representations of the airway’s structure and assists in recognizing structural abnormalities that may result in obstructed airways, while sound monitoring technology records and analyzes snoring and breathing sounds to detect the condition subtly, and thus further expands our medical diagnostic toolkit. As for the future development directions, it can be predicted that interdisciplinary integrated researches, the construction of personalized diagnosis and treatment models, and the popularization of high-tech in clinical applications will become the development trends in the field of OSA evaluation and diagnosis.

The mechanism of L-perilla alcohol(L-POH) in intervening hypoxic pulmonary hypertension(HPAH) was discussed based on network pharmacology, and experimental verification. The active components and potential targets of the volatile oil of Rhodiola tangutica(VORA) in the intervention of HPAH were screened by network pharmacology. The biological process of Gene Ontology(GO) and the signaling pathway enrichment of Kyoto Encyclopedia of Genes and Genomes(KEGG) were analyzed for the core targets, and a "component-common target-disease" network was constructed. Four active components were screened from VORA: L-POH, linalool, geraniol, and(-)-myrtenol. The core targets for treating HPAH were HSP90AA1, AKT1, ESR1, PIK3CA, EP300, EGFR, and JAK2. GO enrichment analysis mainly involved biological processes such as reaction to hypoxia, heme binding, and steroid binding. KEGG enrichment analysis mainly involved hypoxia-inducing factor 1(HIF-1) signaling pathway, phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT) signaling pathway, and Janus kinase/activator of signal transduction and transcription(JAK/STAT) signaling pathway. The vasodilation effects of the four active components were screened by perfusion experiment of extracorporeal vascular rings, and the mechanism of the main active component L-POH was studied by channel blockers. The inhibitory effects of the four active components on the proliferation of pulmonary artery smooth muscle cells(PASMCs) induced by hypoxia were screened by cell proliferation experiment, and the mechanism of the main active component L-POH was studied by flow cytometry, cell cycle experiment, and Western blot. The results showed that L-POH could directly act on vascular smooth muscle to relax pulmonary arterioles, induce ATP-sensitive potassium channels to open, and inhibit extracellular Ca~(2+) influx through voltage-gated calcium channels to relax blood vessels. In addition, L-POH could inhibit the abnormal proliferation of PASMCs induced by hypoxia and promote its apoptosis, and its mechanism may be related to the increase in Bax protein expression and the decrease in p-JAK2, p-STAT3, Bcl-2, and cyclinA2 protein expression. In summary, L-POH can interfere with HPAH by relaxing pulmonary arterioles and inhibiting the proliferation of smooth muscle cells.
Network Pharmacology ; Animals ; Hypertension, Pulmonary/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Hypoxia/metabolism* ; Rhodiola/chemistry* ; Signal Transduction/drug effects* ; Humans ; Monoterpenes/chemistry* ; Male ; Cell Proliferation/drug effects* ; Rats, Sprague-Dawley

OBJECTIVE: To describe survival trends and global patterns of esophageal cancer (EC) using survival data from population-based cancer registries. METHODS: We systematically searched PubMed, EMBASE, Web of Science, SEER, and SinoMed databases for articles published up to 31 December 2023. Eligible EC survival estimates were evaluated according to country or region, period, sex, age group, pathology, and disease stage. RESULTS: After 2010, Jordan exhibited the highest age-standardized 5-year relative survival rates (RSRs)/net survival rates (NSRs) at 41.1% between 2010 and 2014, while India had the lowest, at 4.1%. Survival rates generally improved with diagnostic age across most countries, with significant increases in South Korea and China, of 12.7% and 10.5% between 2000 and 2017, respectively. Survival was higher among women compared to men, ranging from 0.4%-10.9%. Survival rates for adenocarcinoma and squamous cell carcinoma were similar, differing by about 4%. In China, the highest age-standardized RSRs/NSRs was 33.4% between 2015 and 2017. Meanwhile, the lowest was 5.3%, in Qidong (Jiangsu province) between 1992-1996. CONCLUSION Global EC survival rates have improved significantly in recent decades, but substantial geographical, sex, and age disparities still exist. In Asia, squamous cell carcinoma demonstrated superior survival rates compared to adenocarcinoma, while the opposite trend was observed in Western countries. Future research should clarify the prognostic factors influencing EC survival and tailor prevention and screening strategies to the changing EC survival patterns.
Humans ; Esophageal Neoplasms/mortality* ; Registries ; Male ; Female ; Survival Analysis ; Middle Aged ; Survival Rate ; Aged ; Global Health

Objective To develop a modified lentiviral expression system of mCherry-GFP-LC3B,driven by the hematopoietic-specific SFFV(spleen focus-forming virus)promoter,in order to perform an efficient and real-time monitoring of autophagy flux with in terminally differentiated erythroid cells.Methods The lentiviral plasmid pRSC-SFFV-mCherry-GFP-LC3B was constructed and packaged into lentiviruses for infection of human erythroid progenitor cell line(HUDEP-2)and mouse fetal liver-derived primary erythroid cells.Autophagy dynamics of the cells were then analyzed using fluorescence imaging,Western blot,and flow cytometry in serum starvation and chloroquine inter-vention models.Results The SFFV promoter rendered significantly higher reporter expression efficiency than CMV promoter in HUDEP-2(97%vs.60%)(P＜0.01)and in the primary mouse erythroid cells(83%vs.1%)(P＜0.001),without disrupting normal erythroid differentiation.Serum deprivation increased au-tolysosomes(red puncta),elevated LC3-Ⅱ/LC3-Ⅰratios,and decreased p62 levels.Chloroquine treatment in-duced autophagosome(yellow puncta)accumulation(P＜0.001),showing a dose-dependent inhibition of auto-phagy flux(r2=0.92).Conclusions The SFFV-driven dual-fluorescent system enables robust and real-time mo-nitoring of autophagy flux in erythroid cells,providing a sensitive tool for mechanistic study of erythroid differenti-ation and related disorders such as anemia.

Objective: To analyze differences in the expression levels of lipid metabolism-related proteins in adi- pose tissue exosomes between obese mice and wild-type mice using proteomic techniques . Methods: Wild-type (WT) and obese (ob/ob) model mice of the same age were selected , with 8 mice per group . Adipose tissue from both groups was minced and cultured for 48 hours . Conditioned media was collected , and exosomes were isolated u- sing differential centrifugation . Liquid chromatography-tandem mass spectrometry ( LC-MS/MS) was utilized for proteomic analysis to screen differentially expressed proteins ( DEPs) . Gene ontology ( GO) enrichment analysis and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed on the DEPs . Heatmaps were generated to visualize DEPs expression patterns , and Western blot was employed to validate DEPs expression levels . Results: Exosomes were successfully extracted from the culture supernatant of adipose tissues from mice in the WT group and the ob/ob group . Mass spectrometry analysis identified a total of 25 629 peptides and 3 376 proteins . Compared with the WT group , there were 699 proteins with high expression and 632 proteins with low expression in the exosomes derived from adipose tissues of ob/ob mice . Both GO and KEGG analyses showed that DEPs were mainly enriched in metabolic pathways . Heatmap analysis visualized the expression patterns of metabolism-related DEPs , and the expression levels of lipid metabolism-related proteins such as acyl-CoA syn- thetase long-chain family member 1 (ACSL1) , apolipoprotein E (ApoE) , and albumin (Alb) changed significant- ly in the obese state (P < 0. 05) . Western blot verification results showed that the expression of ApoE and Alb pro- teins in the adipose tissue-derived exosomes of ob/ob mice decreased ( P < 0. 01) . Conclusion In the obese state , the expression levels of lipid metabolism-related proteins in mouse adipose tissue exosomes are significantly altered . These differentially expressed proteins may thus serve as potential molecular targets for treating obesity and its associated metabolic complications .

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.

BACKGROUND:Pauwels Ⅲ femoral neck fracture is a typical unstable fracture characterized by high vertical shear force and high incidence of postoperative complications.At present,there are many fixation methods for Pauwels Ⅲ fracture,and there is no clear conclusion as to which internal fixation is the best fixation method for Pauwels Ⅲ femoral neck fracture in young adults. OBJECTIVE:To compare the clinical effect of three inverted triangle cannulated screws assisted transverse lag screws and femoral neck system in fixing Pauwels Ⅲ femoral neck fractures of young adults. METHODS:From May 2021 to December 2022,21 young and middle-aged patients with Pauwels Ⅲ femoral neck fracture were treated with three inverted triangle cannulated screws assisted by transverse lag screws and femoral neck system in Affiliated Hospital of Southwest Medical University.Of them,9 patients were treated with three inverted triangle cannulated screws and one transverse lag screws perpendicular to the fracture line as the 3+1 cannulated screw group and 12 patients were treated with femoral neck system as the femoral neck system group.The two fixation methods were compared in terms of operation time,intraoperative blood loss,total incision length,intraoperative fluoroscopy times,fracture healing time,and limb function. RESULTS AND CONCLUSION:(1)All patients were followed up.Patients in the 3+1 cannulated screw group were followed up for 10-25 months,with a mean of(17.44±4.30)months.The patients in the femoral neck system group were followed up for 8-24 months,with a mean of(15.58±4.68)months.(2)The intraoperative fluoroscopy times and Harris score at 3 months postoperatively in the femoral neck system group were better than those in the 3+1 cannulated screw group,and the difference was statistically significant(P<0.05).The intraoperative blood loss,total incision length,and femoral neck shortening distance in the 3+1 cannulated screw group were better than those in the femoral neck system group,and the differences were statistically significant(P<0.05).There was no significant difference in operation time,fracture healing time,and Harris score at the last follow-up between the two groups(P>0.05).(3)It is indicated that three inverted triangle cannulated screws assisted transverse lag screw and femoral neck system can achieve good clinical effects in the treatment of young and middle-aged Pauwels Ⅲ femoral neck fracture.The femoral neck system has fewer intraoperative fluoroscopy times and better early overall stability,while the 3+1 cannulated screw is more minimally invasive,easier to operate.Both fixation methods are worthy of clinical application and promotion,and can be selected according to the actual clinical situation.

Objective To search for the reports of adverse events of levofloxacin use in children using the FAERS database,and to mine and analyze the data to provide reference for safe clinical use.Methods The data reported of adverse events of levofloxacin use in children from January 1,2004 to June 30,2023 were retrieved through the OpenVigil 2.1 platform,and the relevant data were analyzed based on the reporting odds ratio(ROR)method.Results A total of 484 cases of adverse events of levofloxacin in children were retrieved,and 94 positive risk signals were found.The main systemic organs involved were various musculoskeletal and connective tissues,gastrointestinal system,systemic and administration sites,and the top five positive signals were Dimycodes infection(ROR=822.87),tendon pain(ROR=563.71),Mycobacterium ulcers infection(ROR=352.65),tendon rupture(ROR=341.91),and immune reconstitution inflammatory syndrome-related tuberculosis(ROR=310.84).The top five positive signals not mentioned in the label were Mycobacterium ulcerans infection(ROR=352.65),immune reconstitution inflammatory syndrome-associated tuberculosis(ROR=310.84),central nervous system tuberculoma(ROR=102.85),linear IgA disease(ROR=82.68),and increased intracranial pressure(ROR=32.46).Conclusion In addition to the known adverse events,levofloxacin is used in children,and the risk signal intensity of adverse reactions such as increased intracranial pressure and tuberculosis-related diseases is high,so it is recommended to carefully select and strengthen relevant safety monitoring.

Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.