Diabetic kidney disease （DKD）， a prevalent microvascular complication of diabetes mellitus， is characterized by intricate pathophysiological mechanisms and persistent clinical management challenges. Historically， glomerular injury has been regarded as the central pathological hallmark of DKD， with research predominantly focusing on hyperfiltration， glomerular basement membrane thickening， and podocyte dysfunction. Emerging evidence， however， underscores the renal tubule-not merely as a passive bystander but as an early initiator and pivotal driver-in DKD pathogenesis. Hyperglycemia， metabolic dysregulation， and chronic low-grade inflammation induce tubular epithelial cell injury at early disease stages. Such injury disrupts tubuloglomerular feedback， thereby elevating intraglomerular pressure and sustaining hyperfiltration. Concurrently， injured tubular cells secrete pro-inflammatory cytokines and profibrotic factors， promoting epithelia-mesenchymal transition， interstitial hypoxia， and progressive tubulointerstitial fibrosis that ultimately culminate in irreversible decline of renal function. This "tubule-first" paradigm represents a fundamental shift from the classical glomerulocentric model and redefines the conceptual framework of DKD progression. Traditional Chinese medicine（TCM）， with its inherent advantages of multi-component synergy， multi-target engagement， and systemic homeostatic regulation， has demonstrated compelling renoprotective effect， particularly in preserving tubular integrity and function， mitigating tubular cellular stress， and indirectly alleviating glomerular hemodynamic burden. Accumulating preclinical and clinical evidence supports the efficacy of numerous single herbs and standardized formulae of TCM in attenuating tubulointerstitial injury and slowing down DKD progression. This review systematically delineates the sequential pathogenic cascade-from initial tubular insult to secondary glomerular deterioration-and critically evaluates the mechanism basis and translational potential of TCM-based interventions targeting tubular resilience. We aim to provide a refined pathophysiological rationale and actionable insights for optimizing clinical strategies and accelerating the development of novel therapeutics for DKD.

Diabetic kidney disease （DKD）， a prevalent microvascular complication of diabetes mellitus， is characterized by intricate pathophysiological mechanisms and persistent clinical management challenges. Historically， glomerular injury has been regarded as the central pathological hallmark of DKD， with research predominantly focusing on hyperfiltration， glomerular basement membrane thickening， and podocyte dysfunction. Emerging evidence， however， underscores the renal tubule-not merely as a passive bystander but as an early initiator and pivotal driver-in DKD pathogenesis. Hyperglycemia， metabolic dysregulation， and chronic low-grade inflammation induce tubular epithelial cell injury at early disease stages. Such injury disrupts tubuloglomerular feedback， thereby elevating intraglomerular pressure and sustaining hyperfiltration. Concurrently， injured tubular cells secrete pro-inflammatory cytokines and profibrotic factors， promoting epithelia-mesenchymal transition， interstitial hypoxia， and progressive tubulointerstitial fibrosis that ultimately culminate in irreversible decline of renal function. This "tubule-first" paradigm represents a fundamental shift from the classical glomerulocentric model and redefines the conceptual framework of DKD progression. Traditional Chinese medicine（TCM）， with its inherent advantages of multi-component synergy， multi-target engagement， and systemic homeostatic regulation， has demonstrated compelling renoprotective effect， particularly in preserving tubular integrity and function， mitigating tubular cellular stress， and indirectly alleviating glomerular hemodynamic burden. Accumulating preclinical and clinical evidence supports the efficacy of numerous single herbs and standardized formulae of TCM in attenuating tubulointerstitial injury and slowing down DKD progression. This review systematically delineates the sequential pathogenic cascade-from initial tubular insult to secondary glomerular deterioration-and critically evaluates the mechanism basis and translational potential of TCM-based interventions targeting tubular resilience. We aim to provide a refined pathophysiological rationale and actionable insights for optimizing clinical strategies and accelerating the development of novel therapeutics for DKD.

To explore the clinical significance of decreased serum immunoglobulin (Ig) A levels in patients with IgG4-related disease (IgG4-RD).

Objective: To analyze the whole genome characteristics of Salmonella in diarrhea cases in Hohhot City, so as to provide the evidence for the prevention and control of Salmonella infection and rational clinical use of antibiotics. Methods: Salmonella strains were isolated and identified from fecal specimens of acute diarrhea cases at sentinel hospitals for national foodborne disease surveillance in Hohhot City from 2021 to 2023. DNA was extracted for whole genome sequencing. Bioinformatics analysis based on the Microobench Pathogen Genome Analysis System was conducted to determine serotypes, multi-locus sequence typing (MLST), drug resistance genes, and virulence genes. Additionally, 60 Salmonella genomic sequences from different regions across China were downloaded from the NCBI Genome database. A phylogenetic tree was constructed based on core-genome MLST (cgMLST) to analyze the phylogenetic relationship between strains from Hohhot City and those from other regions of China. Results: From 2021 to 2023, a total of 42 Salmonella strains isolated in Hohhot City were classified into 12 serotypes. Salmonella Enteritidis ST11, Salmonella I 4,[5],12:i:- ST34, and Salmonella Typhimurium ST19 were identified as the dominant strains, represented by 13, 10, and 6 isolates, which accounted for 30.95%, 23.81%, and 14.29%, respectively. Seventy-seven drug resistance genes belonging to 12 classes were detected. Among them, 17 Salmonella strains carried amino acid substitutions in the fluoroquinolone resistance-determining region caused by mutations at the gyrA and parC loci. Virulence genes covered all stages of Salmonella pathogenesis, with a predominance of genes associated with adhesion. Phylogenetic tree analysis results revealed that the 42 Salmonella strains from Hohhot City were distributed across evolutionary branches A, B, C, D, and F. They clustered with 60 strains from other regions of China, suggesting potential cross-regional transmission. Conclusions Salmonella strains isolated in Hohhot City exhibited diverse serotypes, carried multiple drug resistance genes and virulence genes, and displayed high genetic diversity. These findings indicate a potential risk of cross-regional transmission, highlighting the need for enhanced surveillance and prevention measures.

[This corrects the article DOI: 10.1016/j.apsb.2024.03.030.].

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

OBJECTIVES: To compare the efficacy of toric implantable collamer lens (Toric-ICL) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK) for myopia correction in patients with moderate to high myopia complicated with astigmatism. METHODS: We retrospectively collected data from 64 patients (aged 18-42 years) with moderate to high myopia complicated with astigmatism (128 eyes) undergoing either Toric-ICL (28 patients/56 eyes) or FS-LASIK (36 patients/72 eyes) at our department between January, 2019 and December, 2020. The changes of uncorrected distance visual acuity (UCVA), spherical equivalent (SE), mean astigmatism correction index (CI), corneal endothelial cell density (ECD) and intraocular pressure (IOP) following the procedures were compared between the two groups. RESULTS: In FS-LASIK group, all the eyes (72/72) achieved an UCVA≥1.0, similar to the rate in Toric-ICL group (55/56 eyes; P=0.2374). The postoperative SE was also comparable between FS-LASIK and Toric-ICL groups [0.43±0.06 D (range: -1.0 to 1.50 D) vs 0.38±0.05 D (range: -0.75 to 1.00 D); P=0.56]. The mean astigmatism CI was significantly higher in FS-LASIK group than in Toric-ICL group (0.8561 vs 0.7176; P<0.0001), and 88.89% of the eyes in FS-LASIK group and 69.64% in Toric-ICL group had postoperative astigmatism ≤0.50 D. No significant changes were observed in postoperative corneal ECD in FS-LASIK group, whereas ECD decreased significantly after the procedure in Toric-ICL group (P=0.0057). The patients undergoing Toric-ICL exhibited no significant changes of postoperative IOP, but the patients receiving FS-LASIK had significantly reduced IOP after the procedure (P<0.001). CONCLUSIONS Although the patients included in Toric-ICL group had higher myopia and astigmatism, Toric-ICL still showed better predictability and efficacy for astigmatic correction in Toric-ICL group. Toric-ICL is an effective and safe equivalent of FS-LASIK for correcting moderate myopia but can be more advantageous for correcting high myopia with astigmatism.
Humans ; Astigmatism/complications* ; Myopia/complications* ; Keratomileusis, Laser In Situ/methods* ; Retrospective Studies ; Adult ; Visual Acuity ; Adolescent ; Young Adult ; Treatment Outcome ; Male ; Lens Implantation, Intraocular/methods* ; Female ; Phakic Intraocular Lenses ; Intraocular Pressure

Objective:To investigate the protective effect of quercetin against LasB-induced apoptosis, inflammation, and oxidative stress in THP-1 macrophages, providing valuable insights into the use of quercetin as a virulence inhibitor for Pseudomonas aeruginosa infection treatment. Methods:This was an experimental study. The experimental strain was the standard strain. The LasB protein was obtained utilizing protein recombination technology, while the enzyme activity of LasB was assessed through both the Elastin Congo red assay and fluorescently labelled elastin assay. The LasB-induced THP-1 macrophage infection model was established, and quercetin was utilized for intervention. Cell viability was evaluated via CCK-8 assay, while cell morphology was observed under an inverted microscope. Apoptosis detection involved employing both TUNEL and Annexin V/PI staining. The mRNA expression and protein levels of inflammatory cytokines and COX-2 were determined by RT-qPCR and ELISA respectively. Intracellular ROS levels were quantified using the DCFH-DA fluorescent probe. One-way ANOVA was used for statistical analysis, and Tukey test was used for multiple comparisons. Results:The pLasB with a molecular weight of 33 000 and acceptable enzymatic activity (purity>90%), was successfully obtained. THP-1 macrophages treated with pLasB at a concentration of 100 μg/ml presented significantly decreased viability and integrity rate when compared with the normal control group. Additionally, pLasB promoted apoptosis, up-regulated the levels of inflammatory cytokines IL-1α, IL-1β, IL-6, IL-10, IL-12, and TNF-α, increased intracellular ROS fluorescence intensity, and elevated COX-2 mRNA expression level. Furthermore, the viability of THP-1 macrophages was significantly enhanced under quercetin intervention at concentrations of 2.5 μmol/L, 5 μmol/L and 10 μmol/L. The apoptosis rate exhibited a significant reduction from 18.32%±0.17% to 13.17%±0.20%, 11.43%±0.06% and 7.74%±0.04%, respectively ( F=1 679, P<0.05). There was a notable down-regulation of pro-inflammatory cytokines IL-1α, IL-1β, IL-6, IL-12 and TNF-α while the anti-inflammatory cytokine IL-10 showed a significant up-regulation. Both intracellular ROS fluorescence intensity ( F=86.92, P<0.05) and COX-2 level ( F=24.62, P<0.05) demonstrated a substantial decrease. Conclusion:Quercetin demonstrates significant efficacy in inhibiting LasB-induced apoptosis, inflammation, and oxidative stress in THP-1 macrophages, which highlights immense potential as a potent virulence inhibitor of Pseudomonas aeruginosa.

To investigate the clinical assessment of dual-enhanced antiplatelet therapy after cerebrovascular intervention to reduce the risk of cerebral infarction recurrence, and to provide a reference for the prevention and treatment of cerebral infarction recurrence risk. 202 patients with cerebral infarction who underwent cerebrovascular intervention in Tianjin Fifth Central Hospital from January 2018 to October 2022 were selected as study subjects. The patients were divided into a treatment group ( n=104) based on randomized controlled single-blind method with 61 males and 43 females with a mean age of (62.33±2.57) years old and a control group ( n=98) with 56 males and 42 females with a mean age of (62.49±2.36) years old. The control group was given aspirin mono-antiplatelet therapy, and the treatment group was given clopidogrel doublet augmented antiplatelet therapy on the basis of the control group, and both groups continued the treatment for 2 months. Platelet counts, coagulation indexes and inflammatory factors were compared between the two groups before and after treatment, and the America National Institutes of Health Stroke Scale (NIHSS) score was used to assess the neurological functions of the two groups before and after treatment, and the recurrence of cerebral infarction in the two groups was counted within 6 months after treatment. In addition, the patients in the treatment group were divided into the cerebral infarction recurrence group and the cerebral infarction non-recurrence group according to whether they had cerebral infarction recurrence within 6 months after treatment, and the clinical data of the patients in the treatment group were collected to analyze the influencing factors of the dual-enhancement antiplatelet therapy for the recurrence of cerebral infarction in patients with cerebral infarction after cerebral vascular intervention by multifactorial logistic regression. The results showed that after treatment, patients in the treatment group had an international normalized ratio (INR) of (1.76±0.38), a platelet activation rate of (39.52±4.79)%, a platelet aggregation rate of (48.54±5.21)%, a tumor necrosis factor-alpha (TNF-alpha) of (28.37±4.47)ng/L, an interleukin 6 (IL-6) of (24.77±3.52)ng/L, a high-sensitivity C-reactive protein (hs-CRP) of (7.39±1.53)mg/L and an NIHSS score of (6.11±1.39) were lower than those of the control group (2.32±0.41), (44.81±6.37)%, (51.39±5.58)%, (39.66±4.51) ng/L, (29.25±4.04) ng/L, (9.03±1.78) mg/L and (9.93±1.46) points (all P<0.05). At 6-month follow-up of all patients, cerebral infarction recurred in 16 (15.38%) patients in the treatment group and in 33 (33.67%) patients in the control group ( χ2=9.185, P<0.05). Kaplan-Meier results showed a statistically significant difference in the rate of recurrence without cerebral infarction in the treatment group compared with the control group(LogRank χ2=4.595, P<0.05). Logistic regression analysis showed that smoking history, cervical vascular plaque, post-treatment NIHSS score, post-treatment stenosis score, post-treatment INR, post-treatment hs-CRP and CYP2C19 gene polymorphism were independent influences on the recurrence of cerebral infarction in cerebral infarction patients with cerebral vascular interventions followed by doublet augmentation of antiplatelet therapy (all P<0.05). In conclusion, dual-enhanced antiplatelet therapy may be an effective measure to reduce the risk of cerebral infarction recurrence after cerebrovascular intervention in patients with cerebral infarction, but it is still influenced by more factors.

Necroptosis is a regulated process of programmed cell death independent of aspartic acid-specific cysteine protease,which can induce inflammation.Studies have shown that necroptosis is closely related to the progression and prognosis of pancreatic disease and plays an important two-way regulatory role in its progression.Related necroptosis inhibitors and inducers are expected to be used in the treatment of pancreatic disease.We herein review the mechanism of necroptosis and its role in the progression of pancreatic disease to provide a new understanding of the pathogenesis and treatment of pancreatic diseases and offer a theoretical basis for the research and development of targeted drugs.