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.

To investigate the impact of preoperative serum follicle-stimulating hormone (FSH) levels on the probability of testicular sperm retrieval, we conducted a study of nonobstructive azoospermic (NOA) men with different testicular volumes (TVs) who underwent microdissection testicular sperm extraction (micro-TESE). A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital, Shenzhen, China) were retrospectively reviewed. The subjects were divided into four groups based on average TV quartiles. Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups. Overall sperm retrieval rate was 57.6%. FSH levels (median [interquartile range]) were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was <5 ml (first quartile [Q1: TV <3 ml]: 43.32 [17.92] IU l -1 vs 32.95 [18.56] IU l -1 , P = 0.048; second quartile [Q2: 3 ml ≤ TV <5 ml]: 31.31 [15.37] IU l -1 vs 25.59 [18.40] IU l -1 , P = 0.042). Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were <5 ml (adjusted odds ratio [OR]: 1.06 per unit increase; 95% confidence interval [CI]: 1.01-1.11; P = 0.011). In men with TVs ≥5 ml, larger TVs were associated with lower odds of sperm retrieval (adjusted OR: 0.84 per 1 ml increase; 95% CI: 0.71-0.98; P = 0.029). In conclusion, elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs <5 ml. In men with TV ≥5 ml, increases in average TVs were associated with lower odds of sperm retrieval.
Humans ; Male ; Azoospermia/surgery* ; Sperm Retrieval/statistics & numerical data* ; Adult ; Follicle Stimulating Hormone/blood* ; Retrospective Studies ; Testis/pathology* ; Microdissection ; Organ Size

The aim of this study was to investigate the contribution of lung zinc ions to pathogenesis of lung ischemia/reperfusion (I/R) injury in rats. Male Sprague Dawley (SD) rats were randomly divided into control group, lung I/R group (I/R group), lung I/R + low-dose zinc chloride group (LZnCl₂+I/R group), lung I/R + high-dose ZnCl₂ group (HZnCl₂+I/R group), lung I/R + medium-dose ZnCl₂ group (MZnCl₂+I/R group) and TPEN+MZnCl₂+I/R group (n = 8 in each group). Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the concentration of zinc ions in lung tissue. The degree of lung tissue injury was analyzed by observing HE staining, alveolar damage index, lung wet/dry weight ratio and lung tissue gross changes. TUNEL staining was used to detect cellular apoptosis in lung tissue. Western blot and RT-qPCR were used to determine the protein expression levels of caspase-3 and ZIP8, as well as the mRNA expression levels of zinc transporters (ZIP, ZNT) in lung tissue. The mitochondrial membrane potential (MMP) of lung tissue was detected by JC-1 MMP detection kit. The results showed that, compared with the control group, the lung tissue damage, lung wet/dry weight ratio and alveolar damage index were significantly increased in the I/R group. And in the lung tissue, the concentration of Zn²⁺ was markedly decreased, while the cleaved caspase-3/caspase-3 ratio and apoptotic levels were significantly increased. The expression levels of ZIP8 mRNA and protein were down-regulated significantly, while the mRNA expression of other zinc transporters remained unchanged. There was also a significant decrease in MMP. Compared with the I/R group, both MZnCl₂+I/R group and HZnCl₂+I/R group exhibited significantly reduced lung tissue injury, lung wet/dry weight ratio and alveolar damage index, increased Zn²⁺ concentration, decreased ratio of cleaved caspase-3/caspase-3 and apoptosis, and up-regulated expression levels of ZIP8 mRNA and protein. In addition, the MMP was significantly increased in the lung tissue. Zn²⁺ chelating agent TPEN reversed the above-mentioned protective effects of medium-dose ZnCl₂ on the lung tissue in the I/R group. The aforementioned results suggest that exogenous administration of ZnCl₂ can improve lung I/R injury in rats.
Animals ; Reperfusion Injury/pathology* ; Male ; Rats, Sprague-Dawley ; Rats ; Chlorides/administration & dosage* ; Lung/pathology* ; Zinc Compounds/administration & dosage* ; Apoptosis/drug effects* ; Caspase 3/metabolism* ; Cation Transport Proteins/metabolism*

The chemical constituents of Commiphora myrrha was investigated by column chromatography on silica gel, ODS, Sephadex LH-20, and semi-preparative HPLC. Their structures were elucidated by comprehensive spectroscopic methods including UV, IR, MS, NMR, as well as ECD calculation. Seven compounds were isolated from the dichloromethane-soluble fraction of C. myrrha and their structures were identified as(1S,2R,4S,5R,8S)-guaiane-2-hydroxy-7(11),10(15)-dien-6-oxo-12,8-olide(1), commipholide E(2), myrrhterpenoid H(3), myrrhterpenoid I(4), myrrhterpenoid E(5), 2α-methoxy-8α-hydroxy-6-oxogermacra-1(10),7(11)-dien-8,12-olide(6), 8,12-epoxy-1α,9α-hydroxy-eudesma-7,11-diene-6-dione(7). Compound 1 was a new compound and named myrrhterpenoid P. Compound 7 was isolated from Commiphora genus for the first time. Compounds 2, 5, and 6 significantly inhibited nitric oxide(NO) production in LPS-stimulated RAW264.7 cells, with IC_(50) values of(49.67±4.16),(40.80±1.27),(47.22±0.87) μmol·L~(-1), respectively [indomethacin as the positive control, with IC_(50) value of(63.92±2.60) μmol·L~(-1)].
Commiphora/chemistry* ; Animals ; Mice ; Resins, Plant/chemistry* ; Sesquiterpenes/isolation & purification* ; Molecular Structure ; Nitric Oxide ; Macrophages/metabolism* ; RAW 264.7 Cells ; Drugs, Chinese Herbal/pharmacology*

This research investigated the contamination level,distribution of drug-resistant strains,and molecular epidemiologi-cal characteristics of Campylobacter,and further explored transmission pathways and prevention strategies.Cecum,chicken carcass,chicken product,and environmental samples,as well as swabs from workers'hands,were collected from a slaughterhouse in a large broiler group in the Jiaodong area between August 2023 and July 2024.Quantitative contamination assessment of Campylobacter in chicken carcasses and chicken products was performed.After microbial mass spectrometry identification,the representative strains of different links were selected for drug resistance testing and whole genome sequencing(WGS).On the basis of the sequencing results,the resistance genes,virulence genes,multilocus sequence typing(MLST),and phylogenetic characteristics of representative strains were analyzed.Homology comparisons were performed between isolates and strains from patients with diarrhea in the NCBI database.A total of 297 Campylobacter strains were isolated from 806 samples,and the overall detection rate was 36.85%.The detection rate of Campylobacter was highest in the evisceration process(47.33%),followed by the cutting process(35.64%).Overall,the Campylo-bacter detection rate first increased,then decreased,and subsequently increased.Drug sensitivity testing revealed that 90 isolates were resistant to nalidixic acid and ciprofloxacin,and 94.97%of isolates were resistant to tetracycline.WGS showed that both Campylo-bacter jejuni(C.jejuni)and Campylobacter coli(C.coli)carried many drug resistance and virulence genes.ST-14176 of C.jejuni was isolated for the first time herein.The predominant ST-8261 strain of C.jejuni and ST-860,ST-829,and ST-1586 strains of C.coli are known to cause human diarrhea.LOS expression genes associated with Guillain-Barré syndrome(GBS)were detected in both C.jejuni isolates from the slaughter chain and patients with GBS.Some strains exhibited close genetic relatedness to human-derived Campylo-bacter strains from the NCBI database.The detection rate of Campylobacter in the slaughterhouse first increased,then decreased,and subsequently increased,and the quantitative contamination level of each link was similar to the detection rate.Quantitative analysis of chicken carcasses/products revealed that the average bacterial load was highest in eviscerated carcasses(102.80 cfu/g),and the high-est amount of Campylobacter in chicken products reached 451.80 cfu/g.Abundant drug resistance genes and virulence genes were iden-tified,and the drug resistance genes were highly correlated with the drug resistance rate.Therefore,surveillance intensity and control measures for Campylobacter in slaughter processes should be strengthened.

Objective::To examine the impact of hypertensive disorders of pregnancy (HDP) on offspring metabolomics.Methods::We searched five databases: PubMed, Ovid Embase, MEDLINE, Web of Science, and China National Knowledge Infrastructure, and included studies that reported metabolomics among human offspring born to HDP-complicated pregnancies.Results::Database search yielded 4054 articles, and after full-text screening, ten observational studies met inclusion criteria. Half of the studies had a sample size of less than 100 and were all observational studies in preeclampsia (PE) and gestational hypertension.Neonates were the most focused group in all included studies. Offspring born to HDP-complicated pregnancies exhibited statistically significant variations in blood metabolomics compared to their counterparts, characterized by amino acids, lipids, carnitine, and others (e.g., 1α,25-(OH) 2-D). Most studies reported a significant increase in differential metabolites of offspring born to HDP-complicated pregnancies. Four studies ( n = 1109) measured lipids-related metabolites, and all consistently showed that offspring born to PE-complicated pregnancies had significantly higher concentrations than non-PE exposed offspring. Conclusion::The existing evidence suggests an intergenerational effect of HDP on offspring metabolomics. Long-term follow-up studies are needed to advance the health effects of related adverse health outcomes and inform the prevention of offspring’s health.

Objective::To examine the impact of hypertensive disorders of pregnancy (HDP) on offspring metabolomics.Methods::We searched five databases: PubMed, Ovid Embase, MEDLINE, Web of Science, and China National Knowledge Infrastructure, and included studies that reported metabolomics among human offspring born to HDP-complicated pregnancies.Results::Database search yielded 4054 articles, and after full-text screening, ten observational studies met inclusion criteria. Half of the studies had a sample size of less than 100 and were all observational studies in preeclampsia (PE) and gestational hypertension.Neonates were the most focused group in all included studies. Offspring born to HDP-complicated pregnancies exhibited statistically significant variations in blood metabolomics compared to their counterparts, characterized by amino acids, lipids, carnitine, and others (e.g., 1α,25-(OH) 2-D). Most studies reported a significant increase in differential metabolites of offspring born to HDP-complicated pregnancies. Four studies ( n = 1109) measured lipids-related metabolites, and all consistently showed that offspring born to PE-complicated pregnancies had significantly higher concentrations than non-PE exposed offspring. Conclusion::The existing evidence suggests an intergenerational effect of HDP on offspring metabolomics. Long-term follow-up studies are needed to advance the health effects of related adverse health outcomes and inform the prevention of offspring’s health.

AIM To study the chemical constituents from Tylophora ovata(Lindl.)Hook.ex Steud.and their antibacterial activities.METHODS Ethanol extract was isolated and purified by MCI,silica gel,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by spectral data.The inhibitory activities of each compound against Phomopsis sp.were determined by mycelial growth rate method.RESULTS Twenty-six compounds were identified as paeonol(1),stigmast-4-en-3-one(2),ergosta-4,6,8(14),22-tetraen-3-one(3),2,4-methoxyphenol(4),1,2,4-trimethoxybenzene(5),3-methoxyphenol(6),3,4-dimethoxyacetophenone(7),5α,8α-epidioxy-ergosta-6,22(E)-diene-3β-ol(8),kaempferol 3-O-β-D-galactopyranoside(9),glaucogenind C(10),glaucoge-nin A 3-O-β-D-cymaropyranoside(11),dibutyl phthalate(12),cynatratoside A(13),hirundigoside C(14),sublanceoside B2(15),cynanoside A(16),dipentyl phthalate(17),5-hydroxymethyl-2-furancarboxaldehyde(18),bis-(2-ethyl)hexylphthalate(19),p-hydroxybenzoic acid(20),syringic acid(21),β-hydroxypropiovanillone(22),3-hydroxy-l-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone(23),(+)-syringare sinol(24),(-)-syringare sinol(25),(+)-medioresinol(26).IC50 value of compound 12 was 37.27 μg/mL.CONCLUSION Compounds 1-26 are isolated from this plant for the first time.Compound 12 has inhibitory activity against Phomopsis sp.

This research investigated the contamination level,distribution of drug-resistant strains,and molecular epidemiologi-cal characteristics of Campylobacter,and further explored transmission pathways and prevention strategies.Cecum,chicken carcass,chicken product,and environmental samples,as well as swabs from workers'hands,were collected from a slaughterhouse in a large broiler group in the Jiaodong area between August 2023 and July 2024.Quantitative contamination assessment of Campylobacter in chicken carcasses and chicken products was performed.After microbial mass spectrometry identification,the representative strains of different links were selected for drug resistance testing and whole genome sequencing(WGS).On the basis of the sequencing results,the resistance genes,virulence genes,multilocus sequence typing(MLST),and phylogenetic characteristics of representative strains were analyzed.Homology comparisons were performed between isolates and strains from patients with diarrhea in the NCBI database.A total of 297 Campylobacter strains were isolated from 806 samples,and the overall detection rate was 36.85%.The detection rate of Campylobacter was highest in the evisceration process(47.33%),followed by the cutting process(35.64%).Overall,the Campylo-bacter detection rate first increased,then decreased,and subsequently increased.Drug sensitivity testing revealed that 90 isolates were resistant to nalidixic acid and ciprofloxacin,and 94.97%of isolates were resistant to tetracycline.WGS showed that both Campylo-bacter jejuni(C.jejuni)and Campylobacter coli(C.coli)carried many drug resistance and virulence genes.ST-14176 of C.jejuni was isolated for the first time herein.The predominant ST-8261 strain of C.jejuni and ST-860,ST-829,and ST-1586 strains of C.coli are known to cause human diarrhea.LOS expression genes associated with Guillain-Barré syndrome(GBS)were detected in both C.jejuni isolates from the slaughter chain and patients with GBS.Some strains exhibited close genetic relatedness to human-derived Campylo-bacter strains from the NCBI database.The detection rate of Campylobacter in the slaughterhouse first increased,then decreased,and subsequently increased,and the quantitative contamination level of each link was similar to the detection rate.Quantitative analysis of chicken carcasses/products revealed that the average bacterial load was highest in eviscerated carcasses(102.80 cfu/g),and the high-est amount of Campylobacter in chicken products reached 451.80 cfu/g.Abundant drug resistance genes and virulence genes were iden-tified,and the drug resistance genes were highly correlated with the drug resistance rate.Therefore,surveillance intensity and control measures for Campylobacter in slaughter processes should be strengthened.