Renal fibrosis is the common pathological endpoint of many forms of chronic kidney disease (CKD), yet the mechanisms determining effective repair versus persistent fibrotic remodeling remain incompletely understood. Peritubular capillaries (PTCs) are not merely passive targets of fibrotic injury, but form a dynamic vascular microenvironment linking regional perfusion, oxygen delivery, tubular metabolism, endothelial barrier integrity, pericyte support, immune-cell trafficking, and extracellular matrix (ECM) remodeling. We propose that PTC abnormalities should not be interpreted simply as reduced capillary density, but as a multidimensional disturbance of microvascular structure and function. Structural vascular preservation does not necessarily indicate effective microcirculation: anatomically detectable capillaries may still exhibit impaired perfusion, barrier dysfunction, abnormal endothelial-pericyte interactions, disturbed oxygen metabolism, or reduced network connectivity. Conversely, increased angiogenesis does not necessarily signify successful vascular repair if vessels remain immature, poorly perfused, or inadequately integrated into the existing network. To organize these abnormalities, we conceptualize PTC remodeling into four predominant but nonexclusive states: endothelial barrier disruption with inflammatory adhesion; endothelial-pericyte uncoupling with no-reflow; dysregulated angiogenesis with network simplification; and capillary rarefaction with fibrotic matrix locking. These states are not sequential stages of CKD. They may coexist within the same kidney, overlap within the same anatomical region, and vary with disease etiology, injury phase, vascular compartment, and treatment exposure. We further propose six dimensions for evaluating PTC status—structural presence, functional perfusion, barrier integrity, pericyte coupling, oxygen metabolism, and network connectivity—so that vascular quantity, function, and reparative capacity are assessed separately rather than inferred from a single endothelial marker or capillary-density measurement. Mechanistically, these states converge on a bidirectional microvascular-fibrotic feedback loop. Barrier disruption facilitates leukocyte recruitment and alters vascular paracrine signaling. Endothelial-pericyte uncoupling compromises capillary stability, whereas abnormal pericyte contraction may increase local vascular resistance and contribute to no-reflow before overt capillary loss. Dysregulated angiogenesis may generate vessels that fail to mature or connect to an effective perfusion network. Progressive capillary rarefaction compromises oxygen delivery, while sustained tubular transport demand and mitochondrial dysfunction may aggravate regional oxygen supply-demand mismatch. Injured tubules, immune cells, endothelial cells, pericytes, and fibroblasts communicate through soluble mediators, extracellular vesicles, direct cell contact, and cell-matrix signaling. Importantly, fibrosis is not merely a downstream consequence of microvascular injury. Altered ECM may increase diffusion distance, modify mechanotransduction, impair endothelial survival and migration, and restrict capillary reopening and regeneration. We use the term matrix locking to describe this sustained constraint on vascular repair, while emphasizing that current evidence does not establish irreversible disease in humans. This framework also has therapeutic implications. PTC-directed treatment should not be reduced to increasing vessel number or uniformly promoting angiogenesis. Instead, intervention should be matched to the dominant and potentially reversible abnormality: preserving endothelial barrier function; restoring endothelial-pericyte stability and reducing pathological microvascular resistance; normalizing angiogenesis so that vascular growth is accompanied by maturation, barrier competence, network integration, and effective perfusion; and, in advanced rarefaction, relieving matrix-related constraints while supporting vascular regeneration. The context- and time-dependent effects of signaling through VEGF, Tie2, PDGF-B/PDGFRβ, eNOS/NO, and related pathways indicate that the same molecular signal may exert different effects depending on disease context and timing. Therapeutic efficacy should therefore be evaluated by restoration of effective microcirculation and tissue function rather than by isolated molecular changes or capillary counts alone. Despite increasing mechanistic evidence, the translational basis for this framework remains limited. Most causal and interventional data derive from animal or cell models, whereas human evidence is largely limited to pathological observations, patient-sample associations, and prognostic studies. Currently available circulating and urinary candidate biomarkers generally lack sufficient specificity for PTC injury or state assignment, and no standardized quantitative thresholds have been externally validated. The four-state model should therefore be regarded as a hypothesis-generating analytical framework rather than a clinicopathological classification system. Future studies should integrate spatially resolved tissue phenotyping, blood and urine biomarkers, and dynamic microcirculatory assessment in longitudinal cohorts. They should test reproducibility, assess prognostic value beyond conventional pathology, estimated glomerular filtration rate, and proteinuria, and determine whether changes in PTC status precede or mediate therapeutic benefit. Linking reproducible microvascular phenotypes to defined mechanisms, treatment response, and long-term renal outcomes will be essential to determine whether state-directed assessment and restoration of the PTC microenvironment can ultimately inform patient stratification and therapeutic decision-making.

OBJECTIVE: To explore the mechanism of crocin, a major active component of Crocus sativus (Zanghonghua), in regulating amyloid beta (Aβ) generation, endoplasmic reticulum (ER) stress, and autophagy in neuronal cells, with potential therapeutic applications in Alzheimer's disease (AD). METHODS: Mouse neuroblastoma Neuron2a (N2a) cells stably transfected with the human amyloid precursor protein (APP) Swedish mutant was used as a cellular model for AD (N2a/APP). Control cells were vector transfected (N2a/vector). The effects of 3 different doses of crocin on reactive oxygen species (ROS) generation, cytosolic calcium, and apoptosis were evaluated by flow cytometry. Aβ levels were determined by enzyme-linked immunosorbent assay. APP processing and ER stress proteins expressions were determined by Western blot. Autophagosome formation was evaluated by autophagy detection kit and confocal microscope. RESULTS: Crocin inhibited APP expression in N2a/APP cells and promoted α-cleavage of APP processing, while modestly reduced beta-secretase 1 (BACE1) and presenilin 1 (PS1, P<0.05 or P<0.01). ER stress markers, including the binding immunoglobulin protein/78-kD glucose-regulated protein (Bip/GRP78) and C/EBP homologous protein (CHOP), were elevated in N2a/APP cells compared to N2a/vector cells (P<0.05). Crocin could effectively reduce the levels of ER stress (P<0.05 or P<0.01). In addition, crocin enhanced autophagy by promoting formation of autophagosome (P<0.05 or P<0.01). CONCLUSION Crocin significantly inhibited Aβ generation by promoting α-cleavage of APP processing, inhibiting ER stress-associated unfolded protein response, and regulating autophagy.
Endoplasmic Reticulum Stress/drug effects* ; Autophagy/drug effects* ; Animals ; Endoplasmic Reticulum Chaperone BiP ; Mice ; Amyloid beta-Peptides/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Carotenoids/pharmacology* ; Humans ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Calcium/metabolism*

In most types of erectile dysfunction, particularly in advanced stages, typical pathological features observed are reduced parenchymal cells coupled with increased tissue fibrosis. However, the current treatment methods have shown limited success in reversing these pathologic changes. Recent research has revealed that changes in autophagy levels, along with alterations in apoptosis and fibrosis-related proteins, are linked to the progression of erectile dysfunction, suggesting a significant association. Autophagy, known to significantly affect cell fate and tissue fibrosis, is currently being explored as a potential treatment modality for erectile dysfunction. However, these present studies are still in their nascent stage, and there are limited experimental data available. This review analyzes erectile dysfunction from a pathological perspective. It provides an in-depth overview of how autophagy is involved in the apoptotic processes of smooth muscle and endothelial cells and its role in the fibrotic processes occurring in the cavernosum. This study aimed to develop a theoretical framework for the potential effectiveness of autophagy in preventing and treating erectile dysfunction, thus encouraging further investigation among researchers in this area.
Male ; Humans ; Autophagy/physiology* ; Apoptosis/physiology* ; Erectile Dysfunction/physiopathology* ; Fibrosis ; Penis/pathology* ; Animals ; Endothelial Cells/pathology* ; Myocytes, Smooth Muscle/pathology*

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

The Chinese Pharmacopoeia 2025 Edition added the 9213 Guideline for validation,verification,and transfer of microbiological analytical methods.Based on the characteristics of pharmaceutical microbiological analyt-ical methods and practical applications,it specified definitions of relevant terms and application scenarios,estab-lished technical indicators and acceptance criteria for methodological evaluation,and introduced key statistical tools and evaluation principles.This article systematically elaborates on the drafting background and process of the Guideline,and interprets its key content,aiming to offer theoretical guidance and practical reference for relevant practitioners in applying this guideline.This guideline strengthens the foundation of pharmaceutical microbial analytical methods in China and enhances the scientificity and accuracy of the pharmaceutical microbial standards system.

Objective:To preliminarily evaluate the efficacy and safety of a domestically developed bilateral interventional ultrasound renal denervation (RDN) system in patients with uncontrolled hypertension despite antihypertensive medication.Methods:A multicenter, single-arm trial was conducted. Patients with uncontrolled hypertension (≥2 antihypertensive drugs) were enrolled from April 2023 to April 2024 at the Second Affiliated Hospital of Chongqing Medical University, West China Hospital of Sichuan University, and the Second Affiliated Hospital of Harbin Medical University. RDN was performed using the UltraCure? bilateral interventional ultrasound system via femoral or brachial artery access. Multi-segmental "quadrant-based" ablation was performed in bilateral main renal arteries and branches/accessory arteries (diameter≥4 mm). Primary endpoints were changes in office systolic blood pressure (SBP) and 24-hour daytime SBP at 2-and 6-months post-procedure. The primary safety endpoints included the incidence of major adverse events, device-related adverse events, and puncture site complications.Results:Ten patients, mean aged 47.1 years, including 9 male, successfully completed RDN. At 2 and 6 months post-procedure, office SBP decreased by (19.7±15.2) mmHg ( P=0.002, 1 mmHg=0.133 kPa) and (13.8±13.9) mmHg ( P=0.013) from baseline, while the 24-hour daytime SBP decreased by (13.4±10.6) mmHg ( P=0.004) and (11.2±9.2) mmHg ( P=0.004). Apart from one case of a limited distal renal artery dissection, no other serious device/procedure-related adverse events were observed. At 6-month follow-up, the estimated glomerular filtration rate remained stable ((85.3±18.3) ml·min -1·1.73 m -2 vs. (82.3±19.2) ml·min -1·1.73 m -2, P=0.41). No renal artery stenosis was detected. Conclusions:The domestic interventional ultrasound RDN system could effectively reduce office and ambulatory blood pressure in patients with uncontrolled hypertension, demonstrating a favorable safety profile. Long-term efficacy requires confirmation through large-scale randomized controlled trials.

The Chinese Pharmacopoeia 2025 Edition added the 9213 Guideline for validation,verification,and transfer of microbiological analytical methods.Based on the characteristics of pharmaceutical microbiological analyt-ical methods and practical applications,it specified definitions of relevant terms and application scenarios,estab-lished technical indicators and acceptance criteria for methodological evaluation,and introduced key statistical tools and evaluation principles.This article systematically elaborates on the drafting background and process of the Guideline,and interprets its key content,aiming to offer theoretical guidance and practical reference for relevant practitioners in applying this guideline.This guideline strengthens the foundation of pharmaceutical microbial analytical methods in China and enhances the scientificity and accuracy of the pharmaceutical microbial standards system.

Objective:To preliminarily evaluate the efficacy and safety of a domestically developed bilateral interventional ultrasound renal denervation (RDN) system in patients with uncontrolled hypertension despite antihypertensive medication.Methods:A multicenter, single-arm trial was conducted. Patients with uncontrolled hypertension (≥2 antihypertensive drugs) were enrolled from April 2023 to April 2024 at the Second Affiliated Hospital of Chongqing Medical University, West China Hospital of Sichuan University, and the Second Affiliated Hospital of Harbin Medical University. RDN was performed using the UltraCure? bilateral interventional ultrasound system via femoral or brachial artery access. Multi-segmental "quadrant-based" ablation was performed in bilateral main renal arteries and branches/accessory arteries (diameter≥4 mm). Primary endpoints were changes in office systolic blood pressure (SBP) and 24-hour daytime SBP at 2-and 6-months post-procedure. The primary safety endpoints included the incidence of major adverse events, device-related adverse events, and puncture site complications.Results:Ten patients, mean aged 47.1 years, including 9 male, successfully completed RDN. At 2 and 6 months post-procedure, office SBP decreased by (19.7±15.2) mmHg ( P=0.002, 1 mmHg=0.133 kPa) and (13.8±13.9) mmHg ( P=0.013) from baseline, while the 24-hour daytime SBP decreased by (13.4±10.6) mmHg ( P=0.004) and (11.2±9.2) mmHg ( P=0.004). Apart from one case of a limited distal renal artery dissection, no other serious device/procedure-related adverse events were observed. At 6-month follow-up, the estimated glomerular filtration rate remained stable ((85.3±18.3) ml·min -1·1.73 m -2 vs. (82.3±19.2) ml·min -1·1.73 m -2, P=0.41). No renal artery stenosis was detected. Conclusions:The domestic interventional ultrasound RDN system could effectively reduce office and ambulatory blood pressure in patients with uncontrolled hypertension, demonstrating a favorable safety profile. Long-term efficacy requires confirmation through large-scale randomized controlled trials.

Abstract Background and aims Hepatic ischemia-reperfusion injury (HIRI) is a major contributor to liver dysfunction and failure, particularly in the context of liver transplantation. Its pathogenesis is primarily driven by ferroptosis, oxidative stress, and mitochondrial dysfunction. Given the interplay among these mechanisms through redox imbalance and disrupted energy metabolism, nicotinic acid (NA)—recognized for its antioxidative and metabolic regulatory properties—emerges as a promising therapeutic candidate. This study aims to investigate the protective effects of NA on HIRI and elucidate its underlying mechanisms. Methods An HIRI model in mice and a hypoxia/reoxygenation (H/R) model in primary hepatocytes were established to evaluate the effects of NA treatment on oxidative stress. NA was administered prior to model induction. N-acetylcysteine (NAC) was used as a comparator. Comprehensive assessments of ferroptosis, oxidative stress, mitophagy, and mitochondrial biogenesis markers were conducted using Western blotting, immunohistochemistry, immunofluorescence, and biochemical assays. Results NA pretreatment reduced serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase (LDH) levels, suppressed inflammation by decreasing neutrophil infiltration and macrophage activation, and mitigated oxidative stress by lowering reactive oxygen species (ROS) and malondialdehyde (MDA) levels. It enhanced antioxidant defenses, inhibited ferroptosis, and improved mitochondrial health through increased mitophagy, mitochondrial biogenesis, and mitochondrial permeability transition pore (mPTP) stabilization, leading to enhanced ATP production and mitochondrial function in HIRI. Conclusions NA improves mitochondrial function by promoting mitophagy and mitochondrial biogenesis, which reduces ferroptosis and oxidative stress, thereby alleviating HIRI.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.