Lactic acid bacteria (LAB) are promising candidates for live bacterial drug delivery systems owing to their safety, probiotic properties, and ability to colonize the intestinal tract. At present, most research focuses on engineering LAB as carriers for the delivery of therapeutic proteins. As model organisms equipped with a versatile set of genetic tools, LAB can be readily modified to target various diseases and yield significant therapeutic effects. LAB-based carriers offer multiple advantages, including non-invasive delivery, ease of genetic manipulation, and suitability for large-scale production. Consequently, the use of LAB as recombinant protein expression vectors has attracted extensive research interest worldwide. The foundational principles, strategies for enhancing bioavailability, genetic engineering approaches, and the current research and application status of LAB-based drug delivery systems were summarized in this paper.

Objective To understand the characteristics of occupational noise hazards in key industries in Huizhou City. Methods A total of 247 enterprises from 13 key industries in Huizhou City were selected as the research subjects using the stratified judgment sampling method. The worksite survey of occupational health and workplace noise intensity and spectrum monitoring were conducted at key work sites using "questionnaires and on-site inspections" method. Results The rate of noise intensity exceeding national standards was 53.4% (132/247). The median, 25th and 75th percentile of noise pressure levels in workplaces and worksites were 85.1 (81.2, 91.2)and 82.5 (78.8, 86.3) dB(A), respectively. The high-noise workplaces accounted for 50.0% (479/958). The rate of noise intensity exceeding national standard at work sites was 32.9% (303/921). The sound pressure level of noise at work sites was positively correlated with sound pressure level of noise sources (Spearman correlation coefficient=0.73, P<0.01). The top three high-risk work sites for exceeding national noise standards were grinding, frame nailing, and material cutting, with exceedance rates of 84.6%, 81.3%, and 62.8%, respectively. The frequency characteristics of the top ten high-risk work sites were mainly high-frequency noise. There were significant differences in noise spectrum characteristics among different workpiece materials used in similar types of work sites (all P<0.05), though high-frequency noise remained dominant. Conclusion Noise hazards in workplaces of key industries in Huizhou City are relatively severe. Continuous attention should be given to key work sites with high over-standard rate, such as grinding, frame nailing, and material cutting, and noise control strategies should be developed based on frequency spectrum characteristics.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95％of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.

Structural optimization of lead compounds is a crucial step in drug discovery.One optimization strategy is to modify the molecular structure of a scaffold to improve both its biological activities and absorption,distribution,metabolism,excretion,and toxicity(ADMET)properties.One of the deep molecular generative model approaches preserves the scaffold while generating drug-like molecules,thereby accelerating the molecular optimization process.Deep molecular diffusion generative models simulate a gradual process that creates novel,chemically feasible molecules from noise.However,the existing models lack direct interatomic constraint features and struggle with capturing long-range dependencies in macromolecules,leading to challenges in modifying the scaffold-based molecular structures,and creates limitations in the stability and diversity of the generated molecules.To address these challenges,we propose a deep molecular diffusion generative model,the three-dimensional(3D)equivariant diffusion-driven molecular generation(3D-EDiffMG)model.The dual strong and weak atomic interaction force-based long-range dependency capturing equivariant encoder(dual-SWLEE)is introduced to encode both the bonding and non-bonding information based on strong and weak atomic interactions.Addi-tionally,a gate multilayer perceptron(gMLP)block with tiny attention is incorporated to explicitly model complex long-sequence feature interactions and long-range dependencies.The experimental results show that 3D-EDiffMG effectively generates unique,novel,stable,and diverse drug-like molecules,highlighting its potential for lead optimization and accelerating drug discovery.

Objective:To quantitatively analyze right ventricular reverse remodeling in patients with severe tricuspid regurgitation after transcatheter tricuspid edge-to-edge repair (T-TEER) by two-dimensional speckle tracking echocardiography, and to preliminarily evaluate the clinical efficacy of this procedure.Methods:This study was a prospective single-center cohort study. Patients diagnosed with severe tricuspid regurgitation at the Xiamen Cardiovascular Hospital Xiamen University from March 2021 to June 2023 were enrolled. All patients underwent transthoracic echocardiography and transesophageal three-dimensional echocardiography before T-TEER, and transthoracic echocardiography at 30 days, 6 months, and 9 months after T-TEER. The primary endpoint was major adverse cardiovascular and cerebrovascular events, including death, stroke, myocardial infarction, reoperation, arrhythmia, and conduction block. Other clinical evaluation indicators included New York Heart Association (NYHA) functional classification and tricuspid regurgitation grade.Results:A total of 34 patients were enrolled, aged (67.9±9.3) years, and 71% (24/34) were female. The median follow-up duration was 9 months. All patients achieved a reduction of tricuspid regurgitation by ≥2 grades at 9 months after T-TEER, with 79% (27/34) of them having mild to moderate tricuspid regurgitation. Transthoracic echocardiography at 9 months after T-TEER showed that the vena contracta width of tricuspid regurgitation ((5.42±2.33) mm vs. (11.54±4.05) mm, P<0.001), effective regurgitant orifice area ((0.24±0.09) cm2 vs. (0.52±0.14) cm2, P<0.001), regurgitant jet area ((7.95±4.02) cm2 vs. (13.93±6.10) cm2, P<0.001), inferior vena cava diameter ((19.38±2.63) mm vs. (23.56±3.31) mm, P<0.001), right ventricular end-diastolic diameter ((28.03±6.26) mm vs. (33.21±8.24) mm, P=0.001), and tricuspid annular diameter ((36.47±4.40) mm vs. (41.44±7.08) mm, P<0.001) were all reduced compared with baseline; while the tricuspid annular plane systolic excursion ((18.08±5.25) mm vs. (14.91±3.42) mm, P=0.005) and right ventricular fractional area change ((37.61±7.52)% vs. (30.79±9.06)%, P=0.004) were both increased compared with baseline. At 9 months after T-TEER, all patients had a NYHA functional classification of grade Ⅰ or Ⅱ, and no major adverse cardiovascular and cerebrovascular event occurred during the follow-up period. Conclusion:It is preliminarily confirmed that T-TEER is safe and effective in the treatment of severe tricuspid regurgitation, with significant right ventricular reverse remodeling observed in patients at 9 months after T-TEER.

Immunotherapy for cancer,as an emerging treatment modality,has made significant strides in recent years and has become a crucial therapeutic approach following surgery,radiotherapy,chemotherapy,and targeted therapy.In particular,the clinical utilization of immune checkpoint inhibitors(ICIs)has not only enhanced the survival rates of patients with refractory or recurrent tumors but has also significantly optimized the overall strategy for cancer treatment.However,as the population undergoing cancer immunotherapy continues to grow,this expansion not only yields clinical benefits but also precipitates a range of specific adverse reactions known as immune-related adverse events(irAEs).Pleural effusion is a common and severe complication in cancer patients,significantly affecting both their quality of life and treatment outcomes.Typically,tumor-related pleural effusion is often due to pleural metastasis,with malignant pleural effusion(MPE)characterized by rapid growth,being difficult to control,and tendency for recurrence.With the approval of new drugs and the expansion of indications for existing medications,the number of cancer patients receiving ICIs treatment is increasing,bringing ICIs-related pleural effusion into focus.While ICIs treatment-related pleural effusion is relatively rare in clinical practice,it is closely linked to treatment choices of patients and prognosis.Unlike MPE,the pathogenesis of ICIs treatment-related pleural effusion is more complex,not only involving non-specific immune activation leading to autoimmune inflammatory reactions but also potentially related to nodular pleural granulomatous reactions,eosinophilic chronic pleurisy,and tumor-infiltrating lymphocytes.In terms of diagnosis,ICIs treatment-related pleural effusion is typically diagnosed through exclusion,requiring the exclusion of other causes such as tumor progression,radiotherapy,and chemotherapy-induced pleural effusion,adding complexity and difficulty to the diagnostic process.Treatment for ICIs treatment-related pleural effusion often involves glucocorticoids,tocilizumab,or infliximab,aiming to alleviate symptoms and improve prognosis by suppressing excessive immune reactions.Preventing the occurrence of ICIs treatment-related pleural effusion is equally crucial,necessitating comprehensive patient assessment before ICIs administration and continuous monitoring during treatment to promptly detect and manage potential adverse reactions.Through this comprehensive management approach,the impact of ICIs treatment-related pleural effusion on patient quality of life and treatment outcomes can be minimized,optimizing overall treatment results.This review aimed to explore the pathogenesis,histological features,clinical manifestations,diagnostic methods and treatment strategies of ICIs treatment-related pleural effusion,and delve into the characteristics of ICIs treatment-related pleural effusion,in order to enhance understanding of this complication and provide a reference for clinical practice.

Objective To develop a deep learning model based on fundus retinal images to improve the detection rate of mild cognitive impairment(MCI)in patients with coronary heart disease,achieve early intervention and improve prognosis.Methods The study was a single-center cross-sectional study that retrospectively included patients diagnosed with coronary heart disease(CHD)by coronary angiography(≥50％ stenosis of at least one coronary vessel)from Beijing Anzhen Hospital between November 2021 and December 2022.The whole data set was randomly divided into the training set and the testing set according to the ratio of 8∶2 for model development.After that,the patient data of the same center from January 2023 to April 2023 were included in the time verification method to verify the model.The diagnostic criteria for MCI were MMSE＜27 or MoCA＜26.Four kinds of convolutional neural network(CNN)architectures were used to train fundus images,and a comprehensive vision model of MCI detection was established through model integration.The area under the curve(AUC),sensitivity and specificity of the receiver operating curve(ROC)were used to evaluate the performance of the AI model.Results We collected 5 880 eligible fundus images from 3 368 CHD patients.Based on the results of the MMSE scale,the algorithm was labeled,including 2 898 males and 527 MCI patients.The AUC of the deep learning model in the test group is 0.733(95％CI 0.688-0.778),and the sensitivity of the algorithm in the test group is 0.577(95％CI 0.528-0.625)by using the operating point with the maximum sum of sensitivity and specificity.With a specificity of 0.758(95％CI 0.714-0.802),corresponding to a validated AUC of 0.710(95％CI 0.601-0.818).Based on the results of the MoCA scale,the algorithm labels 2 437 males and 1 626 MCI patients.The AUC of the deep learning model in the test group was 0.702(95％CI 0.671-0.733).The operating point with the maximum sum of sensitivity and specificity was selected,and the sensitivity of the algorithm was 0.749(95％CI 0.719-0.778)and the specificity was 0.561(95％CI 0.527-0.595),corresponding to the AUC value of the verification group was 0.674(95％CI 0.622-0.726).Conclusions The deep learning algorithm model based on fundus images has good diagnostic performance,and may be used as a new non-invasive,convenient and rapid screening method for MCI in CHD population.

Objective To investigate the ameliorative effects and mechanisms of six types of tea(green tea,cyan tea,red tea,white tea,black tea and yellow tea)on metabolic disorders in obesity mice induced by high-fat diet(HFD).Methods Four-week-old male C57BL/6J mice were randomly divided into 8 groups with 7 mice per group.An HFD-induced obese mouse model was established,and the mice in control group maintained on standard diet followed by intragastric administration of different teas for 5 weeks.The body weight,liver weight ratio,fasting blood glucose,and lipid profile of the mice were measured to assess glucose and lipid metabolism.Serum inflammatory factors including IL-6,tumor necrosis factor-alpha(TNF-α)and oxidative stress markers[malondialdehyde(MDA)and superoxide dismutase(SOD)were measured.Additionally,liver histopathology and the expression of key glycolipid metabolism-related genes,adenosine monophosphate-activated protein kinase(AMPK)and carnitine palmitoyltransferase 1(CPT-1),were analyzed to explore underlying mechanisms.Results Cyan tea significantly suppressed weight gain,demonstrating superior weight control.White tea markedly reduced fasting blood glucose levels and decreased the area under the curve of oral glucose tolerance test(OGTT)and insulin tolerance test(ITT),indicating synergistic improvements in glucose metabolism and insulin sensitivity.Yellow tea exhibited exceptional anti-inflammatory and antioxidant effects,reducing hepatic IL-6 and MDA while enhancing SOD activity.Green tea activated the lipid oxidation pathway by upregulating AMPK/CPT-1 expression.All kinds of tea significantly attenuated hepatic lipid droplet accumulation.Conclusion All six types of tea alleviated metabolic disorders by reducing hepatic fat content in obesity mice.However,different types of tea exert their unique effects on improving metabolic disorders through differential mechanisms such as glucose metabolism regulation,lipid oxidation,and anti-inflammatory and antioxidant actions.

BACKGROUND:Skin wound repair is an extremely complex process.The nervous system plays an important role in regulating wound repair and scar healing.OBJECTIVE:To review the role of the nervous system in the process of skin wound repair,including the roles of related factors and various cells in the repair of skin injury.METHODS:The PubMed and CNKI databases were searched with the key words of"skin wound healing,nervous system,nerve regeneration,growth factor"in English and"skin wound healing,skin innervation,neuropeptide,growth factor,cell synergy"in Chinese.The time range of literature search was from 2003 to 2024,and 83 documents were finally included and analyzed.RESULTS AND CONCLUSION:(1)The skin is densely innervated by autonomic and sensory nerves,and there is growing evidence that the cutaneous nervous system is not only responsible for transmitting sensory information to the central nervous system,but also plays an important role in a variety of skin functions,including wound healing.(2)The nervous system acts on different stages of skin wound healing,which can regulate revascularization,promote the release of related growth factors and neurotransmitters,and cooperate with different types of cells to promote skin wound healing.Therefore,research on the underlying mechanisms of the nervous system has become a powerful target to promote skin wound healing.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.