Background: Adrenocortical hormones, particularly 11-oxygenated androgens, are pivotal in female reproductive health and fertility. Standardized detection kits and population-specific reference intervals are lacking in China, hindering related clinical applications. Methods: A HPLC-tandem mass spectrometry (HPLC-MS/MS) pipeline was developed, rigorously validated, and applied to simultaneously quantify corticosterone, cortisone, cortisol, 18-OH cortisol, androstenedione (A4), 11β-hydroxyandrostenedione (11-OH A4), dehydroepiandrosterone, and dehydroepiandrosterone sulfate in serum samples from 455 reproductive-aged women (18–45 yrs) in Guangxi, China. Age-dependent concentration trends were analyzed, and reference intervals stratified by age (2.5th to 97.5th percentiles) were established. Correlations with body-composition metrics, ethnicity, and the menstrual cycle were investigated. Results: The HPLC-MS/MS method demonstrated high precision (intra- and inter-assay CVs < 15%), accuracy, and sensitivity. All eight hormones exhibited significant age-related declines (P < 0.001 for seven hormones; P = 0.001 for 11-OH A4). Notably, 11-OH A4 levels were significantly lower in the 35–45-yr (3.05 nmol/L) and 25–34-yr (3.09 nmol/L) age groups than in the 18–24-yr (3.57 nmol/L) age group, whereas no significant difference was observed between the 35–45-yr and 25–34-yr age groups. Weak negative correlations were observed between the body mass index and corticosterone and cortisone levels, whereas ethnicity and the menstrual cycle showed no significant associations with hormone levels. Conclusions We developed an HPLC-MS/MS-based method for simultaneously quantifying eight adrenocortical hormones, including 11-OH A4, and defined age-specific reference intervals for reproductive-aged Chinese women. These findings advance the clinical utility of adrenocortical hormones in diagnosing and managing reproductive disorders.

Acute kidney injury (AKI) is a prevalent and life-threatening clinical syndrome characterised by a rapid decline in renal function and diverse pathological etiologies. The condition has been demonstrated to be associated with elevated mortality rates and an increased risk of progression to chronic kidney disease. At present, clinicians depend heavily on conventional functional markers, such as serum creatinine and urine output, for the diagnosis and staging of the disease. It is evident that these conventional indicators characteristically manifest a considerable temporal delay and only undergo modification subsequent to considerable tissue damage. This severely restricts the timeframe for early detection and timely therapeutic intervention. Furthermore, standard markers fail to provide specific biological information regarding the underlying cellular injury mechanisms. The utilisation of advanced probe technologies in molecular imaging offers a robust alternative to overcome these inherent diagnostic limitations.This comprehensive review systematically evaluates recent progress in the design and application of two primary categories of molecular imaging tools for acute kidney disease, specifically reactive probes and enzyme-activated probes. Reactive probes are engineered to specifically interact with redox-active chemical species, including hydrogen peroxide, peroxynitrite, hypochlorous acid, and sulfur dioxide. Because oxidative stress constitutes a primary early event in acute renal tubular damage, these probes enable researchers and clinicians to visualize early cellular injury and radical accumulation well before global renal functional decline becomes evident. We discuss the application of these reactive probes across multiple imaging modalities including fluorescence imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), and photoacoustic techniques. Photoacoustic imaging combines high spatial resolution with deep tissue penetration and has successfully demonstrated the ability to provide diagnostic alerts up to 12 h before any detectable rise in serum creatinine levels. Additionally, specific reactive probes have shown promising translational potential when tested by high-throughput screening in clinical human urine samples. Enzyme-activated probes target the specific catalytic activity of disease-relevant enzymes. These include well-documented renal tubular structural biomarkers such as NAG, GGT, and ALP, along with apoptosis-related caspases and specific nitroreductases. By responding only to enzymatic cleavage, these tools provide highly specific and pathology-directed imaging readouts. Recent structural design strategies in this field have advanced significantly beyond single-enzyme detection. Researchers are now focusing on sophisticated dual-target recognition to minimize background noise, multimodal integration to cross-validate imaging signals, and theranostic applications where probes simultaneously deliver diagnostic feedback and therapeutic agents to injured tissues. Nanotechnology serves as a fundamental enabler for realizing these advanced probe functions. By precisely optimizing nanoparticle parameters such as hydrodynamic size, surface charge, and targeting ligands, researchers can achieve amplified signal output, highly precise kidney delivery, and protection against premature degradation in the systemic circulation. For example, modifying surface charges can significantly enhance the active uptake of nanoprobes by damaged renal tubular epithelial cells.While preclinical probe development has progressed rapidly, moving these technologies into routine clinical practice remains a major challenge. We analyze the translational feasibility and current obstacles from biological, technological, and regulatory perspectives. Although biological targets such as KIM-1, FAP, and ALP have been validated in extensive patient cohorts, practical barriers severely limit their immediate clinical application. These obstacles involve complex changes in in vivo pharmacokinetics. During an acute injury episode, the extreme drop in the glomerular filtration rate alters probe clearance and can cause unwanted systemic accumulation or confusing background imaging signals. Other major hurdles include a lack of comprehensive long-term toxicity data and the absence of standardized manufacturing protocols to ensure batch-to-batch consistency. Future successful translation will require rigorous multi-center clinical studies to confirm the true diagnostic value of these probes over traditional markers. Researchers must also establish strict standardization of imaging procedures and comprehensive safety evaluations. Ultimately, this review provides a thorough reference framework for designing clinically translatable molecular probes and building a precision diagnostic imaging system for acute kidney injury.

Macrophages are innate immune cells connected with the development of inflammation. Retinoic acid has previously been proved to have anti-inflammatory and anti-arthritic properties. However, the exact mechanism through which retinoic acid modulates arthritis remains unclear. This study aimed to investigate whether retinoic acid ameliorates rheumatoid arthritis by modulating macrophage polarization. This study used retinoic acid to treat mice with adjuvant arthritis and evaluated anti-inflammatory effects by arthritis score, thermal nociceptive sensitization test, histopathologic examination and immunofluorescence assays. In addition, its specific anti-arthritic mechanism was investigated by flow cytometry, cell transfection and inflammatory signaling pathway assays in RAW264.7 macrophages in vitro. Retinoic acid significantly relieved joint pain and attenuated inflammatory cell infiltration in mice. Furthermore, this treatment modulated peritoneal macrophage polarization, increased levels of arginase 1, as well as decreased inducible nitric oxide synthase expression. In vitro, we verified that retinoic acid promotes macrophage transition from the M1 to M2 type by upregulating mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) expression and inhibiting P38, JNK and ERK phosphorylation in lipopolysaccharide-stimulated RAW264.7 cells. Notably, the therapeutic effects of retinoic acid were inhibited by MKP-1 knockdown. Retinoic acid exerts a significant therapeutic effect on adjuvant arthritis in mice by regulating macrophage polarization through the MKP-1/MAPK pathway, and play an important role in the treatment of rheumatic diseases.

Background and Aims:Single-incision laparoscopic cholecystectomy(LC)has become increasingly popular due to its minimal invasiveness and cosmetic advantages,but challenges remain in biliary identification and limited operative space.Indocyanine green(ICG)fluorescence navigation enables real-time visualization of the biliary tract and may enhance surgical safety and efficiency.This study aimed to evaluate the clinical application value of ICG fluorescence navigation in single-incision LC.Methods:A retrospective analysis was conducted on 59 patients with benign gallbladder diseases who underwent elective single-incision LC at Yixing Hospital affiliated to Jiangsu University from January 2023 to December 2024.Patients were divided into a fluorescence group(n=27)and a white-light group(n=32)according to whether ICG fluorescence navigation was applied.The two groups were compared in terms of Calot's triangle dissection time,operative time,intraoperative blood loss,surgeon satisfaction,hospital stay,and postoperative complications.Results:No significant differences were observed in baseline clinical characteristics between the two groups(all P＞0.05).In the fluorescence group,the cystic duct,common hepatic duct,and common bile duct were all successfully visualized.Compared with the white-light group,the fluorescence group had significantly shorter Calot's triangle dissection time[(25.56±3.49)min vs.(38.81±5.59)min],shorter operative time[(44.67±3.06)min vs.(61.31±4.96)min],and less intraoperative blood loss[(13.44±1.70)mL vs.(14.50±2.11)mL](all P＜0.05),with significantly higher surgeon satisfaction(P＜0.05).No intraoperative bile duct injury,conversion to three-port surgery,or postoperative complications occurred in either group.Conclusion:ICG fluorescence navigation can significantly improve biliary identification efficiency in single-incision LC,shorten operative time,reduce blood loss,and enhance surgeon satisfaction,demonstrating promising clinical application prospects.

Objective:To investigate the clinical efficacy of transcranial alternating current stimulation (tACS) combined with drug treatment in patients with bipolar Ⅰ disorder (BD Ⅰ).Methods:Forty-two patients with BD Ⅰ who were admitted to the Mental Health Center Affiliated to Anhui Medical University from March 2022 to June 2023 were included in this randomized double-blind study. These patients were randomly divided into a control group and an observation group using an Excel spreadsheet. In the control group, patients received 10 sessions of sham stimulation in addition to drug treatment, while the observation group received 10 sessions of tACS along with drug treatment. All patients were treated for 2 weeks. Each patient received stimulation for 15 minutes on each of the right and left prefrontal lobes once every working day. The Montreal Cognitive Assessment (MoCA) scores and Bech-Rafaelsen Mania Scale (BRMS) scores were compared between the two groups before and after treatment. Eighteen patients from the observation group and nineteen patients from the control group were included in the final analysis.Results:Two weeks after treatment, the MoCA score in the observation group was higher than that in the control group [(27.39 ± 1.88) vs. (24.63 ± 2.39)], and the BRMS score in the observation group was lower than that in the control group [(15.89 ± 3.18) vs. (19.00 ± 3.32)]. These differences were statistically significant ( t = -3.89, 2.91, both P < 0.05). After treatment, the MoCA score in the observation group increased, while the BRMS score decreased ( t = 5.04, -4.14, both P < 0.05). Pearson correlation analysis indicated the change in MoCA score was negatively correlated with BRMS score in both groups ( r = -0.433, P < 0.05). Conclusions:Drug treatment combined with tACS greatly improved clinical cognitive symptoms and reduced manic symptoms in patients with BD Ⅰ. The combined therapy exhibited better efficacy than monotherapy.

High altitude heart disease(HAHD)is a chronic mountain sickness in which the body is exposed to high altitude(＞2 500 m)hypobaric hypoxia environment for a long time.HAHD has high morbidity and poor prognosis,and pulmonary hypertension is the main causative mechanism for its develop-ment.The phosphodiesterase-5 inhibitor sildenafil has become a hot drug for the treatment of pulmonary hypertension.This paper reviews the progress of HAHD and discusses the mechanism of action and effectiveness of sildenafil in the treatment of HAHD,with a view to providing a basis for the treatment of HAHD with sildenafil.

Central nervous system(CNS)degenerative disorders refer to a spectrum of pathological alterations triggered by struc-tural damage to cerebral neural tissues,clinically manifested as diverse neurological dysfunction syndromes,including multiple sclerosis(MS),neurodegenerative diseases(NDs),and ische-mic stroke.The hallmark pathological features of these disorders involve irreversible neuronal damage and decompensation of functional neural networks,ultimately leading to progressive neurological deficits.Notably,with the accelerating global popu-lation aging,the incidence of these diseases has surged signifi-cantly.According to WHO statistics,they now rank among the top three global causes of disability and mortality.Current re-search has confirmed that the pathogenesis of CNS degenerative disorders exhibits high heterogeneity,encompassing multifaceted pathophysiological processes such as genetic predisposition,oxi-dative stress,protein misfolding,and metabolic dysregulation.This intricate pathogenic network not only complicates clinical differential diagnosis but also poses substantial challenges to the development of precision therapeutic strategies.Importantly,re-cent studies have revealed that mitochondrial homeostasis disrup-tion-induced inflammatory cascades(termed mitochondrial in-flammation)play a pivotal regulatory role in neurodegenerative progression.Key molecular mechanisms include impaired mito-phagy,aberrant mitochondrial DNA(mtDNA)release and NL-RP3 inflammasome activation.This review systematically deci-phers the molecular regulatory network of mitochondrial inflam-mation,with a focus on its biological effects in critical pathologi-cal events such as blood-brain barrier disruption,microglial hy-peractivation and neuronal apoptosis.The overarching aim is to provide a theoretical foundation for developing innovative thera-peutic strategies targeting mitochondrial homeostasis restoration.

Objective To investigate the effect of two treatment regimens combining Tacrolimus(TAC)with different Rituximab(RTX)dosages,and to provide clinical reference for treatment strategies.Methods A retrospective analysis was conducted on patients diagnosed with idiopathic membranous nephropathy(IMN)and treated with RTX combined with TAC regimen(RTX+TAC group and low-dose RTX+TAC group)in The First Affiliated Hospital of Xinxiang Medical University.Propensity score matching(PSM)was performed at a 1:1 ratio,and a total of 60 patients were enrolled,with 30 in each group.In low-dose RTX(375 mg/m2 at the first and fifteenth day respectively)+TAC group,if circulating B cells(CD19?)exceeded 5 cells/μL after 3 months,a 200 mg RTX infusion was administered.In RTX(1g at the first and fifteenth day respectively)+TAC group,if complete remission(CR)was not achieved by 6 months,an additional 1000 mg RTX infusion was administered.The incidence of CR,partial remission,and adverse events were followed up for 12 months after medication in both groups.Results(1)Both groups showed significant reductions in 24-hour proteinuria,with the RTX+TAC group demonstrating a notably higher decrease compared to the low-dose RTX+TAC group.Statistical differences were observed between the two groups at the 1st and 3rd months of treatment(P<0.05).Albumin levels gradually increased,and there were differ-ences between the two groups at both the 1st and 3rd months(P<0.05).The anti-phospholipase A2 antibody levels decreased significantly after one month of treatment[3.45(1.90,22.10)vs.3.28(8.30,23.08)RU/mL],P>0.05.At 3 months of treatment,the overall clinical remission rate was 63.3％for the RTX+TAC group compared to 36.7％for the low-dose RTX+TAC group(P<0.05).At 12 months,the RTX+TAC group achieved an overall remission rate of 86.7％,while the low-dose RTX+TAC group reached 83.3％,showing no statistical significance(P>0.05).After one month of treatment,the RTX+TAC group achieved a complete serological immunological remission rate of 33.3％,significantly higher than the 3.3％in the low-dose RTX+TAC group(P<0.05).(2)The cumulative remission rate of the RTX+TAC group was higher than that of the low-dose RTX+TAC group during the first 6 months of follow-up.The remission rate in the low-dose RTX+TAC group increased significantly after 6 months.Log-rank test showed no statistical difference between the survival curves of the two groups(P=0.37).(3)Based on a multifactorial COX regression analysis of factors related to remission in patients with IMN,for every unit increase in serum immunological remission time,the risk of patients achieving remission decreased by 13.5％(HR=0.87,P=0.016).The risk of remission for patients with high titers of anti-PLA2R antibodies decreased by 60.2％(HR=0.39,P=0.018).Conclusions Different RTX dosages yielded comparable overall clinical remission rates without significantly increasing adverse events.RTX+TAC regimen achieves higher early CR rate.Serological remission time and high titer anti-PLA2R antibodies are associated with clinical outcomes.

Aim To detect the mechanism of Wenshen Jianpi recipe(WSJPR)regulating the autophagy by p70S6K signaling pathway on alleviating podocyte inju-ry in diabetic nephropathy(DN)rats.Methods DN model rats induced by streptozotocin were divided into five groups with six rats in each group:model control group,low dose group(7.5 g·kg-1·d-1),medium dose group(15 g·kg-1·d-1),high dose group(30 g·kg-1·d-1),and positive control group(25 mg·kg-1·d-1).In addition,six normal rats were used as negative control group(isotonic NaCl solution 10 mL·kg-1·d-1).All the rats were given continuous ga-vage for eight weeks.Fasting blood glucose,urine al-bumin/creatinine ratio(UACR)and blood viscosity were determined.The changes of podocyte ultrastruc-ture and autophagosome in each group were observed by transmission electron microscopy(TEM).The pro-tein levels of signaling pathway factor p70S6K and au-tophagy factor p62 in renal tissues of rats in each group were detected by Western blot.Besides,p62 expres-sion was observed by immunohistochemistry.Results WSJPR could decrease fasting blood glucose and UACR,and improve the indexes of blood viscosity in rats.TEM indicated that WSJPR could significantly improve the podocyte ultrastructure and autophagy level in DN rats.Western blot showed that the expression level of signaling pathway factor p70S6K and autophagy factor p62 in the kidney of DN rats increased signifi-cantly compared with blank control group(P＜0.01).The expression level of p70S6K and p62 in WSJPR groups decreased compared with model control group(P＜0.05).Among them,the medium-dose group of WSJPR had the most significant change.Immunohisto-chemical results showed that the level of autophagy fac-tor p62 in kidney tissue of DN rats increased compared with the control group.WSJPR had a certain inhibitory effect on p62 expression in DN rats.Conclusion WSJPR might restore cell homeostasis by inhibiting p70S6K level,reducing the expression of autophagy factor p62 and enhancing autophagy level in renal tis-sue of DN rats.

Objective·To investigate the causal relationship between plasma zinc-alpha-2-glycoprotein 1(AZGP1)and heart failure(HF)by using Mendelian randomization(MR)analysis and experimental validation.Methods·A two-sample MR analysis was performed to assess the causal relationship between AZGP1 and HF by integrating large-scale genome-wide association study(GWAS)data on plasma proteins and HF.The inverse-variance weighted(IVW)method was employed as the primary analytical approach,supplemented by MR-Egger regression,weighted median,and simple median methods.Horizontal pleiotropy was tested by using MR-PRESSO global test and MR-Egger intercept analysis.Colocalization analysis was conducted to validate genetic locus overlap.Additionally,a clinical cohort(84 HF patients and 68 healthy controls)was analyzed,with plasma AZGP1 levels quantified by enzyme-linked immunosorbent assay(ELISA).Results·MR analysis showed that elevated plasma AZGP1 levels were significantly associated with reduced HF risk(OR=0.82,95%CI 0.75?0.90,P=1.70×10-5).Colocalization analysis confirmed that AZGP1 expression and HF shared causal genetic variants(posterior probability for H4=0.69).Sensitivity and reverse MR analyses supported the robustness of the results.ELISA confirmed that plasma AZGP1 levels were significantly lower in HF patients compared to healthy controls,reinforcing its protective role in HF.Conclusion·This study demonstrates AZGP1 exerts a protective causal effect on HF and may serve as a potential biomarker for HF treatment.