AIM: To investigate the influence of relevant inflammatory markers in peripheral blood on the progression of neovascular glaucoma(NVG)secondary to diabetic retinopathy(DR)patients.METHODS: Retrospective case-control study. Patients were categorized into two groups based on the presence or absence of NVG: those with proliferative diabetic retinopathy(PDR)alone(PDR group, n=148)and those with NVG secondary to PDR(NVG secondary to PDR group, n=142). Peripheral blood inflammatory markers were evaluated, including white blood cell-related indices, neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio(PLR), monocyte-to-lymphocyte ratio(MLR), and systemic immune-inflammation index(SII). The distinctions in peripheral blood inflammatory markers between the two groups of patients and their relationships with NVG secondary to PDR were analyzed.RESULTS:No statistically significant differences were observed in basic characteristics between the two groups, confirming their comparability. However, significant differences were found in eosinophil percentage and MLR between the PDR group and the NVG secondary to PDR group(all P<0.05), with both values being significantly higher in the NVG secondary to PDR group. Multivariate Logistic regression analysis revealed that the eosinophil percentage and the MLR were factors influencing the development of patients with NVG secondary to PDR.CONCLUSION: Eosinophil percentage and MLR may be associated with the progression of PDR to NVG, and could serve as potential predictive markers for NVG development in PDR patients.

Antibiotic adjuvants offer a promising strategy for restoring antibiotic sensitivity, expanding antibacterial spectra, and reducing required dosages. Previously, compound 15 was identified as a potential adjuvant for Polymyxin B (PB) against multidrug-resistant (MDR) Pseudomonas aeruginosa DK2; however, its clinical utility was hindered by high cytotoxicity, uncertain in vivo efficacy, and an unclear synergetic mechanism. To address these challenges, we synthesized and evaluated a series of novel benzamide derivatives, with A22 emerging as a particularly promising candidate. A22 demonstrated potent synergistic activity to PB, minimal cytotoxicity, improved water solubility, and broad-spectrum synergism of polymyxins against various clinically isolated MDR Gram-negative strains. In vivo studies using Caenorhabditis elegans and mouse models further confirmed the efficacy of A22. Moreover, A22 effectively suppressed the development of PB resistance in Pseudomonas aeruginosa DK2. Mechanistic investigations revealed that A22 enhances polymyxins activity by inducing reactive oxygen species production, reducing ATP levels, increasing NOX activity, and inhibiting biofilm formation, leading to bacterial death. These findings position A22 as a highly promising candidate for the development of polymyxin adjuvants, offering a robust approach to combating MDR Gram-negative bacterial infections.

OBJECTIVE: Paridis Rhizoma (Chonglou in Chinese), a traditional Chinese herbal medicine, has been shown have strong anti-tumor effects. Paris saponin VII (PSVII), an active constituent isolated from Paridis Rhizoma, was demonstrated to significantly suppress the proliferation of BxPC-3 cells in our previous study. Here, we aimed to elucidate the anti-pancreatic ductal adenocarcinoma (PDAC) effect of PSVII and the underlying mechanism. METHODS: Cell viability was determined by CCK-8, colony formation, and cell migration assays. Cell apoptosis and reactive oxygen species (ROS) production were measured by flow cytometry with annexin V/propidine iodide (Annexin V/PI) and 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), respectively. Pyroptosis was evaluated by morphological features, Hoechst 33342/PI staining assay, and release of lactate dehydrogenase (LDH). JC-1 fluorescent dye was employed to measure mitochondrial membrane potential. Western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to determine the levels of proteins or mRNAs. The effect in vivo was assessed by a xenograft tumor model. RESULTS: PSVII inhibited the viability of PDAC cells (BxPC-3, PANC-1, and Capan-2 cells) and induced gasdermin E (GSDME) cleavage, as well as the simultaneous cleavage of Caspase-3 and poly (ADP-ribose) polymerase 1 (PARP). Knockdown of GSDME shifted PSVII-induced pyroptosis to apoptosis. Additionally, the effect of PSVII was significantly attenuated by Z-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethylketone (Z-DEVD-FMK), on the induction of GSDME-dependent pyroptosis. PSVII also elevated intracellular ROS accumulation and stimulated Bax and Caspase-3/GSDME to conduct pyroptosis in PDAC cells. The ROS scavenger N-acetyl cysteine (NAC) suppressed the release of LDH and inhibited Caspase-9, Caspase-3, and GSDME cleavage in PDAC cells, ultimately reversing PSVII-induced pyroptosis. Furthermore, in a xenograft tumor model, PSVII markedly suppressed the growth of PDAC tumors and induced pyroptosis. CONCLUSION These results demonstrated that PSVII exerts therapeutic effects through Caspase-3/GSDME-dependent pyroptosis and may constitute a novel strategy for preventing chemotherapeutic resistance in patients with PDAC in the future.

Atopic dermatitis (AD) is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching. The colonization of Staphylococcus aureus (S. aureus) is correlated with the severity of the disease, but its role in AD development remains elusive. Using single-cell RNA sequencing, we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S. aureus (MRSA). Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology. Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march. Mechanistically, IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33, which in turn aggravated type 2 immunity and AD-like skin conditions. Overall, these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.
Dermatitis, Atopic/genetics* ; Interleukins/metabolism* ; Animals ; Methicillin-Resistant Staphylococcus aureus/immunology* ; Mice ; Keratinocytes/microbiology* ; Humans ; Interleukin-33/immunology* ; Inflammation/microbiology* ; Staphylococcal Infections/microbiology* ; Disease Models, Animal ; Hypersensitivity/microbiology* ; Mice, Inbred C57BL

Objective: To investigate the relationship between relative grip strength and hyperuricemia (HUA) levels in university freshmen, and to explore the potential value of muscle function indicators in HUA prevention among young populations, so as to provide new scientific evidences for HUA control in the demographic. Methods: Utilizing health examination data from 1 744 freshmen enrolled in a Shaanxi Province university in September 2024, absolute grip strength was measured using CAMRY electronic dynamometers, with relative grip strength subsequently calculated. Spearman correlation analysis was employed to examine relationships between student characteristics and relative grip strength, and binary Logistic regression models assessed the association strength between relative grip strength and HUA. Results: The overall HUA detection rate among freshmen was 29.8%, with significant gender differences (male:43.1%; female:24.0%; χ 2=64.62, P <0.01). Correlation analysis revealed significant associations between relative grip strength, body weight, height, body mass index (BMI) and HUA in both genders (boys: r =-0.27, 0.54, 0.11 , 0.53; girls: r =-0.18, 0.33, 0.08, 0.33, all P <0.05). Binary Logistic regression demonstrated that each standard deviation increase in relative grip strength reduced HUA risk by 77% in males ( OR=0.23, 95%CI =0.14-0.37) and 80% in females ( OR=0.20, 95%CI =0.11-0.36) (both P <0.01). Conclusions Relative grip strength represents a significant factor associated with HUA in university students. Incorporating muscle strength training into HUA prevention programs and establishing muscle function based HUA risk warning systems should be considered.

Data analysis models may assist the transmission of traditional Chinese medicine （TCM） experience and clinical diagnosis and treatment， and the possibility of constructing a “data-knowledge” dual-drive model was explored by taking gastric precancerous state as an example. Data-driven is to make clinical decisions around data analysis， and its syndrome-differentiation decision-making research relies on hidden structural models and partially observable Markov decision-making processes to identify the etiology of diseases， syndrome elements， evolution of pathogenesis， and syndrome differentiation protocols； knowledge-driven is to make use of data and information to promote decision-making and action processes， and its syndrome-differentiation decision-making research relies on convolutional neural networks to improve the accuracy of local disease identification and syndrome differentiation. The “data-knowledge” dual-driven model can make up for the shortcomings of single-drive numerical simulation accuracy， and achieve a balance between local disease identification and macroscopic syndrome differentiation. On the basis of previous research， we explored the construction method of diagnostic assisted decision-making platform for gastric precancerous state， and believed that the diagnostic and decision-making ability of doctors can be extended through the assistance of machines and algorithms. Meanwhile， the related research methods were integrated and the core features of gastric precancerous state based on TCM syndrome differentiation and endoscopic pathology diagnosis and prediction were obtained， and the elements of endoscopic pathology recognition based on TCM syndrome differentiation were explored， so as to provide ideas for the in-depth research and innovative application of cutting-edge data analysis technology in the field of intelligent TCM syndrome differentiation.

Objective To analyze the prevalence, annual trends, and co-morbidity trends of common chronic diseases among workers in a large automotive industry from 2019 to 2021, and to provide a scientific basis for the health management of workers in the automotive industry. Methods The health examination data of workers in a large automotive industry from 2019-2021 were analyzed. Trends in the prevalence of chronic diseases and co-morbidities were analyzed using Join Point software and trend χ² test. Results The prevalence of metabolic syndrome, hyperuricemia, and fatty liver in the 2019 – 2021 health checkups of workers in this enterprise increased at an average rate of 9.27%, 11.35%, and 3.99% per year, respectively. The prevalence of metabolic syndrome, hyperuricemia, and fatty liver in male workers showed an increasing trend at an average rate of 7.05%, 9.25%, and 2.91% per year, respectively. The prevalence of metabolic syndrome in female workers showed an increasing trend at an average rate of 20.76% per year. The prevalence of metabolic syndrome, hyperuricemia and fatty liver was on the rise in the age groups ≤ 29 years old and 40 – 49 years old. The proportion of metabolic syndrome and its co-morbidity with one or two common chronic diseases showed an increasing trend. Conclusion The prevalence and co-morbidity of common chronic diseases in this enterprise are generally on the rise. The enterprise should focus on health education and preventive care for chronic diseases among workers aged ≤ 29 and 40 – 49 years old and male workers and control the annual increasing trend of metabolic syndrome among female workers and workers in the age group ≤ 29 years.

Objective:To explore the clinical phenotype and genetic etiology for a Chinese pedigree affected with Autosomal dominant polycystic kidney disease (ADPKD).Methods:A pedigree with ADPKD diagnosed at the Department of Gynaecology of the First Affiliated Hospital of Zhengzhou University in December 2020 was selected as the study subject. Clinical data of the pedigree was collected, and whole exome sequencing (WES) was carried out for the proband. Candidate variants were verified by Sanger sequencing of the proband and her relatives. This study was approved by the First Affiliated Hospital of Zhengzhou University (Ethics No. KS-2018-KY-36).Results:Fetal ultrasonography showed increased volume and parenchymal echogenicity in both kidneys. The fetus was found to harbor c. 11098C>T (p.R3700C) and c.11039T>C (p.F3680S) compound heterozygous variants of the PKD1 gene, which were respectively inherited from its mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be likely pathogenic (PM1+ PM2_Supporting+ PP3). Conclusion:The c. 11098C>T (p.R3700C) and c. 11039T>C (p.F3680S) compound heterozygous variants of the PKD1 gene probably underlay the ADPKD in the fetus. Above finding has provided guidance for the genetic counseling and prenatal diagnosis for this pedigree.

Objective:To investigate the effect of dexamethasone mixed with ropivacaine for cervical nerve pathway blockade on the postoperative swallowing function in patients undergoing thyroid surgery.Methods:This was a prospective randomized controlled trial. One hundred twenty-four patients, regardless of gender, aged 18-60 yr, of American Society of Anesthesiologists Physical Status classification Ⅰor Ⅱ, who underwent elective thyroidectomy at Xuzhou Cancer Hospital from March to December 2023, were selected and divided into test group (DR group, n=62) and control group (R group, n=62)using a random number table method. After induction of total intravenous anesthesia, bilateral cervical nerve pathway blockade was performed, dexamethasone 5 mg and 0.25% ropivacaine 10 ml were injected in DR group, and 0.25% ropivacaine 10 ml was injected in group R. Main outcome measures: The swallowing function was assessed using Standard Swallowing Assessment scale at 1 and 6 days postoperatively, and the occurrence of swallowing dysfunction (abnormal in any indicator) was recorded. Secondary outcome measures: numerical rating scale scores were recorded immediately after tracheal extubation and at 4, 8, 12, 24 and 48 h after tracheal extubation in both static and swallowing states. Voice function was evaluated using the Voice Handicap Index-10 at 1 and 6 days postoperatively. The use of ketorolac tromethamine and occurrence of adverse reactions after surgery were recorded. Results:Sixty-one patients were finally included in DR group and 60 patients in R group. Compared with R group, the Standard Swallowing Assessment scale scores at 1 and 6 days after operation and incidence of swallowing disorders at 1 day after operation were significantly decreased, the numerical rating scale scores at 8 and 12 h after tracheal extubation in the static state and at 4-24 h after tracheal extubation in the swallowing state were decreased, the incidence of postoperative nausea and vomiting and Voice Handicap Index-10 scores at 1 day after operation were decreased, and the number of patients who used ketorolac tromethamine was reduced in DR group ( P<0.05). Conclusions:Dexamethasone mixed with ropivacaine for cervical nerve pathway blockade can improve the postoperative swallowing function in patients undergoing thyroid surgery.

Objective:To investigate the clinical features and prognosis of patients with choroidal tuberculoma.Methods:A retrospective and observational study. From 2011 to 2022, 15 patients (16 eyes) with choroidal tuberculoma diagnosed and treated in Department of Ophthalmology, Shanghai Eye & ENT Hospital of Fudan University were included. The patients underwent examinations including best corrected visual acuity (BCVA), fundus color photography, optical coherence tomography (OCT), fluorescein fundus angiography (FFA), and indocyanine green angiography (ICGA). Chest CT examination, purified protein derivative test and interferon-γ release test were also performed. BCVA was performed using the Snellen visual acuity chart, which was converted to Logarithm of the minimum angle of resolution (logMAR) visual acuity when recorded. All the patients received antitubercular therapy and the duration was 12-15 months. Thirteen patients were combined with oral corticosteroids. The average follow-up time was 36 months. Rank sum test was used to compare logMAR BCVA before and after treatment.Results:Among the 15 patients, 5 were male and 10 were female; 1 case was bilateral involvement; 7 patients had a strong positive tuberculin skin test; 8 patients had a positive interferon-γ release assay. Six patients had pulmonary tuberculosis. One patient had peritoneal tuberculosis. Lesions were located in the posterior pole in 12 eyes, 1 eye with papillary tuberculoma. Peripheral lesions were found in 4 eyes. There were 9 eyes each with anterior segment inflammation or vitreous inflammation; 7 eyes were with exudative retinal detachment. OCT examination revealed a hyporeflective thickening of the choroidal stroma, the corresponding elevation of the retina, and often accompanied by subretinal fluid. FFA revealed hyperfluorescence of the mass and fluorescence accumulation with subretinal fluid at the late stage. ICGA revealed hypofuorescence of the lesion. The lesions subsided after treatment, and there was no recurrence during follow-up period. Cataract surgery was performed in 4 eyes due to complicated cataract. One eye undergone vitrectomy due to secondary rhegmatogenous retinal detachment. Anti-vascular endothelial growth factor therapy was performed in 1 eye due to secondary choroidal neovascularization. Ocular wall perforation occurred in 1 eye, and the condition was stable after treatment. Before treatment, the average logMAR BCVA was 1.02±0.57, which improved to 0.31±0.35 after treatment. The difference between the mean logMAR BCVA before and after treatment was statistically significant ( P<0.05). Conclusions:Combination of medical history, clinical manifestations, laboratory tests, and imaging can assist in the diagnosis of choroidal tuberculoma. The main manifestations are subretinal yellowish-white lesions in posterior pole. Standardized anti-tuberculosis therapy can effectively improve the prognosis of vision.