Renal Fanconi syndrome (FS) is a rare renal manifestation of primary Sjögren's syndrome (pSS). This study aims to analyze the clinical and prognostic characteristics of patients with pSS-associated renal FS (pSS-FS) and provide insights for clinical management.

Cancer remains a leading cause of global mortality, necessitating the development of advanced therapeutic strategies with enhanced efficacy and reduced systemic toxicity. Among promising bioactive agents, lactoferrin (LF)—a multifunctional iron-binding glycoprotein abundantly found in mammalian milk and exocrine secretions—has garnered significant interest for its potent and multifaceted anti-cancer properties. This review provides a comprehensive analysis of the current understanding of LF’s role in oncology, encompassing its structural biology, diverse mechanisms of action, and groundbreaking advancements in its application through nano-engineering. LF exerts anti-tumor effects through multiple pathways, including extracellular action, intracellular action, and immune regulation. It demonstrates a remarkable affinity for cancer cell membranes, binding to overexpressed anionic components such as glycosaminoglycans and sialic acids, as well as to specific receptors including the low-density lipoprotein receptor-related protein-1 (LRP-1). This selective binding facilitates targeted uptake. Upon internalization, LF orchestrates a direct assault by inducing cell-cycle arrest in phases such as G0/G1 or S phase through the modulation of key regulators including cyclins, CDKs, and p53. Furthermore, it promotes programmed cell death via apoptotic pathways, involving caspase activation and downregulation of anti-apoptotic proteins such as survivin. A more recently elucidated mechanism is the induction of ferroptosis, an iron-dependent form of cell death characterized by overwhelming lipid peroxidation. Beyond direct cytotoxicity, LF acts as a potent immunomodulator. It enhances natural killer (NK) cell activity, modulates T-lymphocyte populations, and crucially reprograms tumor-associated macrophages (TAMs) from a pro-tumor M2 state to an anti-tumor M1 state, thereby reversing the immunosuppressive tumor microenvironment (TME). The translation of LF’s potential has been significantly accelerated by nanotechnology. The inherent biocompatibility and natural tumor-targeting capabilities of LF make it an ideal platform for sophisticated drug-delivery systems. This review details various fabrication strategies for LF-based nanoparticles (NPs), including self-assembly, sol-in-oil emulsion, and electrostatic nanocomplexes, among others. Research demonstrates that nano-formulations not only protect LF from degradation but also enhance its bioactivity and anti-cancer potency. More importantly, LF NPs serve as versatile carriers for a wide array of therapeutic agents, including conventional chemotherapeutics, natural compounds, and imaging agents. These engineered systems enable synergistic therapy and facilitate site-specific delivery. Notably, the ability of LF to bind to receptors on the blood-brain barrier (BBB) has been leveraged to develop nano-systems for glioblastoma treatment. Other innovative designs utilize LF to modulate the TME—for instance, by alleviating tumor hypoxia to sensitize cells to radiotherapy and chemotherapy. Despite compelling pre-clinical evidence, the clinical translation of LF and its nano-formulations remains nascent. While early-phase trials have established a favorable safety profile for recombinant human LF, larger Phase III studies have yielded mixed results, underscoring the complexity of its action in humans. Key challenges include enhancing drug targeting, optimizing loading efficiency, ensuring batch-to-batch reproducibility, and achieving deep tumor penetration. Future research must focus on the rational design of next-generation LF-NPs. This entails developing standardized manufacturing protocols, engineering “smart” stimuli-responsive systems for targeted drug release in the TME, and constructing multi-targeting platforms. A concerted interdisciplinary effort is paramount to bridge the gap between bench and bedside. In conclusion, LF, particularly in its nano-engineered forms, represents a highly promising and versatile agent in the oncological arsenal, holding immense potential for precise and effective cancer therapy.

Cancer remains a leading cause of global mortality, necessitating the development of advanced therapeutic strategies with enhanced efficacy and reduced systemic toxicity. Among promising bioactive agents, lactoferrin (LF)—a multifunctional iron-binding glycoprotein abundantly found in mammalian milk and exocrine secretions—has garnered significant interest for its potent and multifaceted anti-cancer properties. This review provides a comprehensive analysis of the current understanding of LF’s role in oncology, encompassing its structural biology, diverse mechanisms of action, and groundbreaking advancements in its application through nano-engineering. LF exerts anti-tumor effects through multiple pathways, including extracellular action, intracellular action, and immune regulation. It demonstrates a remarkable affinity for cancer cell membranes, binding to overexpressed anionic components such as glycosaminoglycans and sialic acids, as well as to specific receptors including the low-density lipoprotein receptor-related protein-1 (LRP-1). This selective binding facilitates targeted uptake. Upon internalization, LF orchestrates a direct assault by inducing cell-cycle arrest in phases such as G0/G1 or S phase through the modulation of key regulators including cyclins, CDKs, and p53. Furthermore, it promotes programmed cell death via apoptotic pathways, involving caspase activation and downregulation of anti-apoptotic proteins such as survivin. A more recently elucidated mechanism is the induction of ferroptosis, an iron-dependent form of cell death characterized by overwhelming lipid peroxidation. Beyond direct cytotoxicity, LF acts as a potent immunomodulator. It enhances natural killer (NK) cell activity, modulates T-lymphocyte populations, and crucially reprograms tumor-associated macrophages (TAMs) from a pro-tumor M2 state to an anti-tumor M1 state, thereby reversing the immunosuppressive tumor microenvironment (TME). The translation of LF’s potential has been significantly accelerated by nanotechnology. The inherent biocompatibility and natural tumor-targeting capabilities of LF make it an ideal platform for sophisticated drug-delivery systems. This review details various fabrication strategies for LF-based nanoparticles (NPs), including self-assembly, sol-in-oil emulsion, and electrostatic nanocomplexes, among others. Research demonstrates that nano-formulations not only protect LF from degradation but also enhance its bioactivity and anti-cancer potency. More importantly, LF NPs serve as versatile carriers for a wide array of therapeutic agents, including conventional chemotherapeutics, natural compounds, and imaging agents. These engineered systems enable synergistic therapy and facilitate site-specific delivery. Notably, the ability of LF to bind to receptors on the blood-brain barrier (BBB) has been leveraged to develop nano-systems for glioblastoma treatment. Other innovative designs utilize LF to modulate the TME—for instance, by alleviating tumor hypoxia to sensitize cells to radiotherapy and chemotherapy. Despite compelling pre-clinical evidence, the clinical translation of LF and its nano-formulations remains nascent. While early-phase trials have established a favorable safety profile for recombinant human LF, larger Phase III studies have yielded mixed results, underscoring the complexity of its action in humans. Key challenges include enhancing drug targeting, optimizing loading efficiency, ensuring batch-to-batch reproducibility, and achieving deep tumor penetration. Future research must focus on the rational design of next-generation LF-NPs. This entails developing standardized manufacturing protocols, engineering “smart” stimuli-responsive systems for targeted drug release in the TME, and constructing multi-targeting platforms. A concerted interdisciplinary effort is paramount to bridge the gap between bench and bedside. In conclusion, LF, particularly in its nano-engineered forms, represents a highly promising and versatile agent in the oncological arsenal, holding immense potential for precise and effective cancer therapy.

ObjectiveTo reveal the effects of overexpression and knockdown of CDH18 gene on cervical cancer proliferation and migration levels through the Wnt/β-catenin signaling pathway in cervical cancer cells. MethodsA comprehensive analysis of CDH18-interacting molecules was performed via the bioinformatics STRING database （http：//cn.string-db.org）. Molecular docking between Wnt/β-catenin inhibitor XAV939 and β-catenin was performed using the bioinformatics tool AutoDock （http：//autodock.scripps.edu）. The effect of CDH18 on β-catenin subcellular distribution was detected by laser confocal microscopy. EdU assay， wound healing assay and Transwell assay were used to detect the effects of CDH18 gene overexpression， CDH18 gene knockdown and the XAV939 on cell proliferation and migration. Western blot was performed to measure the expression levels of Wnt/β-catenin pathway-related molecules， including β-catenin， transcription factor 4 （TCF4）， and cellular myelocytomatosis oncogene （c-Myc）， following CDH18 gene overexpression， CDH18 gene knockdown， or XAV939 treatment. ResultsIn SiHa and HeLa cells， CDH18 gene overexpression significantly increased the protein expression levels of β-catenin， TCF4 and c-Myc， decreased the protein expression of GSK-3β， and enhanced cell proliferation and migration， with statistically significant differences （P<0.05）. Conversely， CDH18 gene knockdown significantly reduced the protein expression of β-catenin， TCF4 and c-Myc， elevated GSK-3β expression， and suppressed cell proliferation and migration （P<0.05）.Treatment with XAV939 in SiHa and HeLa cells downregulated β-catenin， TCF4 and c-Myc， upregulated GSK-3β， and inhibited cell proliferation and migration， with significant differences （P<0.05）. ConclusionCDH18 promotes the proliferation and migration of cervical cancer cells via the Wnt/β-catenin signaling pathway.

Objective To evaluate the correlation between soluble programmed cell death-ligand 1(PD-L1)and clinical features of patients with unstable angina pectoris(UAP),and analyze its correlation with prognosis.Methods A total of 171 UAP patients treated in our hospital from April 2021 to October 2023 were recruited retrospectively,and according to adverse cardiovascular events occurred or not within 6 months of follow-up,they were divided into good prognosis group(137 cases)and poor prognosis group(34 cases).Fasting venous blood sample of 4 ml was collect-ed to detect the levels of soluble PD-L1,LDL-C,HDL-C,hs-CRP,hs-cTnI,IL-6,IL-10 and TNF-α.Pearson correlation analysis was used to analyze the correlation between soluble PD-L1 level and clinical features of the UAP patients,and logistic regression model was employed to evaluate the correlation between soluble PD-L1 and the occurrence of adverse cardiovascular events in the UAP patients.ROC curve analysis was applied to evaluate its performance in predicting the clini-cal prognosis,and its AUC value was calculated.Results The poor prognosis group had signifi-cantly lower LDL-C level and LVEF value,but higher levels of HDL-C,hs-CRP,hs-cTnI,IL-6,IL-10,TNF-α and soluble PD-L1 than the good prognosis group(P＜0.05,P＜0.01).Pearson cor-relation analysis showed that soluble PD-L1 level was positively correlated with hs-CRP level(r=0.502,P=0.000).Multivariate logistic regression analysis indicated that the levels of hs-CRP,hs-cTnI and soluble PD-L1 were independent influencing factors for major cardiovascular adverse events in the UAP patients(OR=2.872,95％CI:1.069-7.717,P=0.036;OR=1.667,95％CI:1.022-2.717,P=0.040;OR=1.152,95％CI:1.023-1.297,P=0.019).ROC curve anal-ysis revealed that soluble PD-L1 had high predictive value for clinical prognosis of UAP patients,with an AUC value of 0.942,a sensitivity of 82.35％and a specificity of 94.16％.Conclusion The increased level of soluble PD-L1 increases the risk of major adverse cardiovascular events in UAP patients.Soluble PD-L1 can be used as a potential new biomarker to predict the clinical prognosis of patients.

Objective To explore the mechanism of action of tanthine in the treatment of allergic rhinitis(AR)complicated with asthma in rats by regulating microRNA-27a-3p(miR-27a-3p)targeting thymic stromal lymphopoietin(TSLP).Methods The AR-asthma rat model was established using ovalbumin(OVA)sensitization and nasal drip attack method.Fifty rats were divided into control group(equal volume 0.9％NaCl),model group(AR-asthma model+equal volume 0.9％NaCl),experimental group(AR-asthma model+100 mg·kg-1 xanthortin)and miR-27a-3p inhibitor group(caudal vein injection of 0.5 nmol·μL-1 miR-27a-3p inhibitor 10 μL on the basis of the experimental group),si-TSLP group(0.5 nmol·μL-1 si-TSLP 10 μL intravenously injected on the basis of miR-27a-3p inhibitor group),10 rats in each group.Serum immunoglobulin E(IgE),interleukin-2(IL-2),IL-13 and tumor necrosis factor-α(TNF-α)levels of rats were detected by enzyme-linked immunosorbent assay.The level of superoxide dismutase(SOD)was detected by xanthoxine oxidase method.The level of malonaldehyde(MDA)was detected by thiobarbituric acid method(TBA).Results The levels of IgE in control group,model group,experimental group,miR-27a-3p inhibitor group and si-TSLP group were(18.33±3.53),(89.95±17.62),(55.70±10.08),(78.43±15.30)and(47.87±9.44)ng·mL-1,respectively;IL-2 levels were(8.01±1.36),(19.61±3.94),(14.12±2.51),(17.33±3.18)and(11.89±2.03)pg·mL-1,respectively;IL-13 levels were(6.79±1.33),(34.15±7.02),(24.70±5.13),(35.97±7.24)and(20.53±4.26)pg·mL-1,respectively;TNF-α levels were(94.08±19.07),(312.47±58.61),(209.78±41.49),(296.42±55.99)and(187.45±37.28)pg·mL-1,respectively;SOD levels were(29.14±5.04),(13.25±2.63),(24.19±4.89),(17.28±3.16)and(33.94±5.87)U·mg prot-1,respectively;MDA levels were(2.26±0.51),(4.43±0.72),(3.17±0.58),(3.94±0.69)and(2.62±0.45)nmol·m gprot-1,respectively.The above indicators were compared between control group and model group,model group and experimental group,experimental group and miR-27a-3p inhibitor group,miR-27a-3p inhibitor group and si-TSLP group.The differences were statistically significant(all P＜0.05).Conclusion Xanthine can improve oxidative stress and reduce inflammation of AR complicated with asthma in rats,and its mechanism may be related to the regulation of miR-27 a-3p targeting TSLP.

Objective:To investigate the anti-heart failure mechanism of N-acetylcysteine(NAC)in diabetic cardiomyop-athy independent from coronary artery factors.Methods:A total of 40 diabetic mice after heart failure model construction were randomly divided into two groups,NAC group(n=20,NAC 100mg·kg-1·d-1)and control group(n=20,Saline 100 mg·kg-1·d-1).Echocardiography was performed to detect left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),left ventricular ejection fraction(LVEF),mitral left ventricular early-dias-tolic peak flow velocity/left ventricular late-diastolic peak flow velocity(E/A),isovolumic relaxation time(IVRT)and cardiac output(CO)after 4 weeks.Terminal uridine nick-end labeling(TUNEL)was performed to detect apoptosis in-dex,and Western Blot was performed to detect the expression of extracellular regulated protein kinases(ERK)1/2 after 6 weeks in two groups.Results:Compared to those in control group,mice in NAC group had significant higher LVEF[(40.5±3.4)％vs.(36.9±3.2)％],E/A[(1.5±0.1)vs.(1.4±0.1)]and CO[(10.3±0.6)ml/min vs.(9.9±0.5)ml/min](P＜0.05 or＜0.01);and significant lower LVESV[(23.1±1.3)μl vs.(24.7±1.5)μl],apoptosis index[(31.2±0.5)％vs.(45.1±0.9)％]and the expression of ERK1/2[(2.2±0.2)vs.(3.9±0.1)](P＜0.001 all).Conclusion:NAC exerts anti-heart failure effect by attenuating apoptosis of cardiomyocytes via regulating ERK1/2 pathway.

With the deepening of molecular biology and cell biology research,the regulatory mechanism of autophagy has been gradually revealed,providing new ideas for the treatment of numerous diseases.Autophagy may be closely related to pathological changes such as apoptosis resistance of fibroblast-like synoviocytes,disturbances in bone metabolic homeostasis,and antigen presentation,the regulation of autophagy homeostasis may be an important approach for the treatment of rheumatoid arthritis(RA).In this paper,we provide a review on the pathological mechanism of autophagy in RA,with a view to providing a theoretical basis for later studies.

Objective To compare the therapeutic efficacy of a self-locking zero-notch interbody fusion device for long-segment cervical spondylosis in elderly patients with traditional titanium plate combined with interbody fusion device.Methods From Jan 2019 to Jan 2021,elderly patients(>60 years)with 3-4 segments(C3-C7)radiculopathy,myelopathy,or mixed-type cervical spondylosis underwent anterior cervical discectomy and fusion(ACDF)using a zero-notch interbody fusion device(Group A,n=24)and ACDF using a titanium plate combined with an interbody fusion device(Group B,n=18).We recorded the surgery duration,blood loss,incision length and hospital stay,measure preoperative and postoperative intervertebral height,functional segment height and cervical lordosis,and also observe treatment outcomes and postoperative complications between the two groups.Results There were no statistically significant differences between the two groups in terms of gender,age,Japanese Orthopaedic Association(JOA)score,visual analogue scale(VAS)of upper limb,Neck Disability Index(NDI),preoperative intervertebral height,functional segment height and cervical lordosis.Blood loss,surgery time and hospital stay were similar in both groups,but Group A had shorter incision length(P<0.01)compared with Group B.There were no significant differences between the two groups in JOA scores,upper limb VAS and postoperative NDI,and even in postoperative intervertebral height,functional segment height and cervical lordosis recovery.Conclusion The zero-notch interbody fusion device is effective for treating long-segment cervical spondylosis.Compared with the traditional titanium plate combined with an interbody fusion device,it can avoid postoperative dysphagia with smaller incision and shorter surgery time,which makes it more suitable for elderly patients.

Objective To investigate the impacts of epidural anesthesia with ropivacaine combined with dezocine on lower limb motor nerve block and maternal and infant outcomes in primipara undergoing painless delivery.Methods A total of 159 primiparas who delivered in Nanjing Jiangbei Hospital were selected as the research objects,and divided into the blank group(53 cases),the ropivacaine group(53 cases)and the combined group(53 cases)by the random number table method.Parturients in the blank group were given natural delivery mode,parturients in the ropivacaine group were given ropivacaine epidural anesthesia,and parturients in the combined group were given dezocine anesthesia on the basis of ropivacaine.Analgesic effect at different time points,time of the first,second and third stage of labor,pressing times of analgesic pump,lower limbs motor nerve block,maternal and infant outcomes,and adverse reactions of parturients were compared among the three groups.Results At 10 minutes after analgesia,60 minutes after analgesia,when the cervix was fully dilated and when the fetus was delivered,the VAS scores of the parturients in the ropivacaine group and the combined group were lower than those in the blank group(P<0.05),and the VAS scores of the parturients in the combined group were significantly lower than those in the ropivacaine group(P<0.05).There was no significant difference in the time of the first,second or third stage of labor of parturients among the three groups(P>0.05);The pressing times of analgesic pump of parturients in the combined group was significantly less than that in the ropivacaine group(P<0.05).There was no statistically significant difference in terms of low limb motor nerve block after painless labor of parturients among the three groups(P>0.05).There were no statistically significant differences in the perineal incision rate or the Apgar scores of newborns at 1 minute and 5 minutes after birth among the three groups(P>0.05).The usage rate of forceps and the rate of conversion to cesarean section in the combined group were significantly lower than those in the ropivacaine group and the blank group(P<0.05).There was no statistically significant difference in the incidence of total adverse reactions among the blank group,the ropivacaine group and the combined group(P>0.05).Conclusion The combination of ropivacaine and dezocine for epidural anesthesia has a better analgesic effect on primiparas with painless delivery,has a smaller impact on lower limb motor nerve block in parturients,and can achieve better maternal and infant outcomes.