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.

This paper analyzed the characteristics of peer psychological counseling conducted by class committee member for psychology in universities and the dilemmas they faced in four aspects， including dual relationships， confidentiality issues， competence issues， and informed consent. It also examined the causes of these ethical dilemmas and corresponding countermeasures one by one. Specific work requirements were proposed for class committee member for psychology in conducting peer psychological counseling. These encompassed clarifying the nature and boundaries of the helping relationship， establishing appropriate settings， discussing the impacts of dual relationships， maintaining confidentiality awareness， adopting appropriate confidentiality measures， actively participating in training to improve competence， making timely referrals when exceeding their professional scope， ensuring proper informed consent， and maintaining value neutrality. Recommendations were also put forward for universities to strengthen the training and management of class committee member for psychology， enhance their ethical awareness， and ensure the effectiveness of peer counseling.

Objective To evaluate the current status in the implementation of GBZ/T 201.5-2015 Radiation shielding requirements for radiotherapy rooms-Part 5: Radiotherapy room of proton accelerators, identify issues in the application of its technical indicators, and provide a basis for the in-depth implementation and further revision of the standard. Methods In accordance with the Standardization Law of the People’s Republic of China and the Guidelines for Health Standards Tracking Evaluation (WS/T 536-2017), a combination of cluster sampling and stratified sampling methods was employed to select professionals involved in proton accelerator radiotherapy devices and facilities in three provinces (or municipalities directly under the central government) as the subjects of the survey. A questionnaire was developed to collect basic information about the subjects and their understanding and application of the technical indicators in the standard. A standard evaluation indicator system with a total score of 100 points was established to score the implementation of the standard (40 points), the technical content (30 points), and the effectiveness of the implementation (30 points). Results A total of 169 professionals from 107 institutions participated in the survey, with 79.88% of the respondents having at least 5 years of experience in radiation therapy and 74.56% holding intermediate or higher professional titles. The score of standard implementation was 18.3 points. The awareness rate exceeded 80%, indicating a high level of awareness about the standard. However, the scores for the dissemination and application of the standard were relatively low, accounting for 28% and 32% of their respective full marks. The technical content of the standard and the effectiveness of its implementation scored 27.0 and 26.6 points, respectively. The overall score in the evaluation of standard implementation was 72 points, with scores of 68.6, 72.3, and 75.0 for Beijing City, Shanghai City, and Jiangsu Province, respectively. Conclusion GBZ/T 201.5-2015 Radiation shielding requirements for radiotherapy rooms-Part 5: Radiotherapy room of proton accelerators is scientific and operable, and it is well-coordinated with relevant laws and standards. However, considering the development in FLASH technology and multi-chamber radiotherapy room, it is necessary to revise and improve the standard.

Objective To analyze the correlation between inflammation indicators(systemic inflammatory response syndrome and systemic immune-inflammation index)and adverse outcomes in patients with symptomatic stroke during hospitalization.Methods This study was a prospective cohort study including consecutive patients with symptomatic stroke who were hospitalized in Fuwai Hospital from January to September 2023.The past medical history,clinical symptoms and signs of the patients were collected.The neurological damage was evaluated with National Institute of Health Stroke Scale(NIHSS).Laboratory test results were recorded and the SIRI and SII in-dex were calculated.Patients were followed up for 90 days after the stroke,and their neurological outcomes were evaluated using the modified Rankin Scale.A score of 0-1 was classified as good outcome,and a score ≥2 was classified as poor outcome.The correlation between inflammatory response indicators and poor outcomes was as-sessed using multiple Logistic regression.Results A total of 97 patients with in-hospital symptomatic stroke were included with an average age of 61.8±12.7 years.Among them,there were 28 females(28.9％,28/97),9 with a history of prior stroke(9.3％,9/97),15 with atrial fibrillation(15.5％,15/97),16 with heart failure(16.5％,16/97),and 7 with myocardial infarction(7.2％,7/97).Correlation analysis showed that the NIHSS score at the time of stroke onset was significantly correlated with the patient's post-stroke SIRI(r=0.237,P＜0.05)and SII(r=0.234,P＜0.05).After 90 days of follow-up,41 cases(42.3％,41/97)had a poor outcome.Multiple Logistic regression analysis showed that post-stroke SIRI(Or=4.71,95％CI:1.24-17.90)and SII(Or=3.13,95％CI:0.88-11.06)were correlated with poor outcomes within 90 days after the stroke.Analysis using restricted cubic splines showed that as the levels of SIRI and SII increased,the risk of poor out-comes in patients with in-hospital symptomatic stroke increased.Conclusions SIRI is an independent risk factor for poor outcomes in patients with in-hospital symptomatic stroke,and the risk of poor neurological outcomes in-creases with high level of SIRI.

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.

Objective:To formulate refined management strategies to improve the operation quality and protective effect of medical X-ray diagnosis equipment based on the risk analysis of the correlation of medical X-ray diagnostic equipment.Methods:The used 41 medical X-ray diagnosis equipment in Fuwai Hospital,Chinese Academy of Medical Sciences from January 2022 to December 2023 were selected.According to different management modes for equipment,they were managed respectively by the conventional management mode(20 units)and the management mode with risk analysis of the correlation(21 units).The risk grades of correlation of management mode with risk analysis of the correlation were classified on the basis of the probability of risk and the degree of harm in medical X-ray diagnosis equipment.The protection management of equipment was conducted from three aspects included the location of equipment,the staffs and subjects.A self-made questionnaire was used to investigate the satisfactions of engineers of using management for equipment,operators,and staffs of operating and maintaining equipment for the two kinds of management modes.The protection quality,failure rate of equipment,and qualification rate of protection of medical X-ray diagnosis equipment under different management modes were compared.Results:The quality scores of operation safety,regular inspection,maintenance and repair,and shielding protection for radiation of medical X-ray diagnosis equipment that adopted the management mode with risk analysis of the correlation were respectively(92.14±3.36),(91.47±2.41),(92.54±3.32)and(91.69±3.57)points,all of which were higher than those of the conventional management mode,and the differences of them were statistically significant(t=16.396,17.368,19.688,14.401,P<0.05).The failure rate of the 21 medical X-ray diagnosis equipment that adopted the management mode with risk analysis of correlation was 0,which was lower than 20.00%of the conventional management mode.The qualified rate of protection was 95.23%,which was higher than 70.00%of the conventional management mode,and the differences of them were statistically significant(x2=4.654,4.608,P<0.05).The satisfaction scores of engineers of using equipment,operators and staffs of operating and maintaining equipment for the protective effect of adopting the management mode with risk analysis of correlation were respectively(94.69±4.02),(93.21±4.36)and(92.54±3.47)points,all of which were higher than those of the conventional management mode,and the differences were statistically significant(t=16.902,11.291,12.020,P<0.05).Conclusion:The process-based protection management strategy on the basis of risk analysis of correlation for medical X-ray diagnosis equipment can prevent risks of medical X-ray diagnostic equipment,and improve the operation quality of the equipment,and reduce the operation risks of the equipment,and maximize the enhancement for management quality of medical X-ray diagnosis equipment.

BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

PANoptosis is a type of programmed cell death regulated by the PANoptosome with key features of pyroptosis, apoptosis and/or necroptosis. As the most complex programmed cell death, PANoptosis emphasizes the compensatory role among multiple programmed cell deaths, and can regulate malignant phenotypes such as proliferation, migration, and invasion of tumor cells through multiple signaling pathways, thus affecting malignant tumor progression. It has been found that PANoptosis plays a dual role in tumor progression and treatment. Therefore, it is clinically important to understand the molecular mechanisms by which PANoptosis affects tumorigenesis, development and progression. This paper reviews the molecular mechanisms of apoptosis, pyroptosis and necroptosis, and discusses the activation and regulation mechanisms of PANoptosis and PANoptosome as well as the research progress on the role of PANoptosis in tumors, aiming to provide new ideas for cancer treatment and prognostic assessment.
Humans ; Neoplasms/physiopathology* ; Pyroptosis/physiology* ; Apoptosis/physiology* ; Necroptosis/physiology* ; Signal Transduction ; Animals

Grounded in the theory of "all marrows dominated by brain", this study explored the therapeutic mechanism of Zuogui Pills in modulating the oxytocin(OXT)/oxytocin receptor(OXTR) feed-forward loop in the treatment of postmenopausal osteoporosis(PMOP). A PMOP rat model was established using ovariectomy, and 70 Sprague-Dawley female rats were randomly divided into the following groups: sham operation group, model group, estradiol group(17β-estradiol, 0.05 mg·kg~(-1)·d~(-1)), Zuogui Pills low, medium, and high dose groups(0.2, 0.4, 0.8 g·kg~(-1)·d~(-1), respectively), and an antagonist group(atosiban 0.9 mg·kg~(-1)·d~(-1) + 17β-estradiol 0.05 mg·kg~(-1)·d~(-1) + Zuogui Pills 0.4 g·kg~(-1)·d~(-1)). After 12 weeks of model establishment, treatment was administered by gavage once daily for another 12 weeks, followed by sample collection. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of estrogen(E_2), OXT, tartrate-resistant acid phosphatase(TRACP-5b), and bone alkaline phosphatase(BALP). Histopathological changes in the left distal femur were observed through hematoxylin and eosin(HE) staining. Micro-computed tomography(micro-CT) was used to analyze the microstructure of the right distal femur. Western blot was employed to detect the expression levels of OXTR, small GTP-binding protein Ras, Raf1 proto-oncogene(Raf1), mitogen-activated protein kinase kinase 1/2(MEK1/2), and extracellular signal-regulated kinase 1/2(ERK1/2), and their phosphorylated forms in tibial tissues. Compared with the model group, the Zuogui Pills medium and high dose groups showed significantly increased levels of E_2, OXT, and BALP, with a notable decrease in TRACP-5b levels. Morphologically, the trabeculae in the left distal femur were more tightly arranged. The fibrous structure in the right distal femur was significantly improved in the Zuogui Pills high dose group. Additionally, the expression of OXTR, Ras, p-Raf1, p-MEK1/2, and p-ERK1/2 proteins in tibial tissues was significantly increased. The therapeutic effect of the Zuogui Pills high dose group was partially inhibited when an OXTR antagonist was administered. These findings suggest that Zuogui Pills can regulate the OXT/OXTR feed-forward loop, activate the phosphorylation of the downstream Ras/Raf1/MEK/ERK signaling pathway, and ultimately improve bone mineral density, thereby exerting therapeutic effects in PMOP.
Animals ; Rats, Sprague-Dawley ; Rats ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Oxytocin/genetics* ; Receptors, Oxytocin/genetics* ; Humans ; Osteoporosis, Postmenopausal/genetics* ; Bone and Bones/drug effects* ; Brain/drug effects* ; Bone Marrow/drug effects*