AIM:To investigate the effect of ranibizumab on blood flow density in different regions of the macula in patients with macular edema(ME)secondary to ischemic and non-ischemic branch retinal vein occlusion(BRVO).METHODS:This retrospective study enrolled patients with BRVO-ME who were treated at the hospital from September 2019 to March 2021. Patients were divided into ischemic and non-ischemic groups based on fundus findings. All patients received intravitreal injections of ranibizumab once monthly for three consecutive months. Best corrected visual acuity(BCVA), central macular thickness(CMT), and macular blood flow density were measured before treatment and at 1 d, 1 wk, 1 and 3 mo after treatment.RESULTS: A total of 46 patients(46 eyes)with BRVO-ME were included, comprising 21 eyes in the ischemic group(7 males, 14 females; mean age 55.81±10.36 y)and 25 eyes in the non-ischemic group(11 males, 14 females; mean age 54.84±9.81 y). At 3 mo after treatment, BCVA(LogMAR)in the non-ischemic group was superior to that in the ischemic group(0.19±0.19 vs 0.38±0.27, P=0.009). Analysis of CMT changes showed that the reduction amplitude in the ischemic group was significantly greater than that in the non-ischemic group at both 1 and 3 mo after treatment(all P<0.05). Blood flow densities in the whole, parafoveal, and perifoveal regions of the superficial capillary plexus(SCP), as well as in the whole and perifoveal regions of the deep capillary plexus(DCP), were significantly lower in ischemic patients than in non-ischemic patients, while blood flow density in the foveal region of DCP was significantly higher in the ischemic group(all P<0.05).CONCLUSION: Ranibizumab is effective for both types of patients. Non-ischemic patients have a better long-term visual prognosis, and the advantage may be related to better blood flow perfusion patterns in specific areas 3 mo after treatment. Monitoring changes in blood flow density in these areas can help provide personalized treatment for patients.

Objective To explore the predictive value of forkhead box P3 (FOXP3) mRNA expression in cord blood derived regulatory T cells (Tregs) and the associated cytokines interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) for early-onset atopic dermatitis (AD) in infants. Methods The healthy full-term newborns delivered vaginally at Shanghai Fifth People’s Hospital from September 2023 to April 2024 were enrolled. Umbilical vein blood was collected at birth to measure FOXP3 mRNA expression by RT-PCR and IL-10 and TGF-β concentrations by ELISA. Follow-up was performed at 6 weeks, 3 months, and 6 months postnatally via telephone or outpatient visits to assess the occurrence of AD in infants. Based on the occurrence of AD at 6 months of age, the infants were divided into an AD group and a control group. The indicators related to mothers and infants were compared between the two groups. Logistic regression analysis was used to identify risk factors for the development of AD in infants within 6 months after birth, and a predictive model was constructed. The performance of the model in predicting early-onset AD was evaluated using receiver operating characteristic (ROC) curve analysis. Results A total of 59 infants completed 6-month follow-up, with 17 (28.8%) diagnosed with AD. No significant differences were observed in gestational age, sex, birth weight, presence of siblings, smoking expossure, maternal dietary preferences (egg, milk, or seafood intake), maternal age and education level, or cord blood IL-10 levels between two groups. There were significant differences in season of birth, family history of atopic disease, feeding method, and cord blood levels of FOXP3 mRNA and TGF-β between two groups (P＜0.05). Logistic regression analysis showed low levels of cord blood FOXP3 mRNA and TGF-β, and family history of atopic disease were risk factors for early-onset AD in infants (P＜0.05). A predictive model was constructed using risk factors. The area under the curve of the combined model was 0.821 (95%CI 0.680–0.962), with a sensitivity of 76.5% and a specificity of 85.7%. Conclusion Reduced cord blood FOXP3 mRNA and TGF-β level, and a family history of atopic diseases could be used to predict early-onset AD in infants.

Cancer immunotherapy is currently a very promising therapeutic strategy for treating tumors. However, its effectiveness is restricted by insufficient antigenicity and an immunosuppressive tumor microenvironment (ITME). Pyroptosis, a unique form of programmed cell death (PCD), causes cells to swell and rupture, releasing pro-inflammatory factors that can enhance immunogenicity and remodel the ITME. Nanomaterials, with their distinct advantages and different techniques, are increasingly popular, and nanomaterial-based delivery systems demonstrate significant potential to potentiate, enable, and augment pyroptosis. This review summarizes and discusses the emerging field of nanomaterials-induced pyroptosis, focusing on the mechanisms of nanomaterials-induced pyroptosis pathways and strategies to activate or enhance specific pyroptosis. Additionally, we provide perspectives on the development of this field, aiming to accelerate its further clinical transition.

ObjectiveThe full name of vertebroplasty is percutaneous vertebroplasty (PVP). It is a clinical technique that injects bone cement into the diseased vertebral body to achieve strengthening of the vertebra. The research on the safety and efficacy of bone cement is the basis for clinical application. In this study, vertebroplasty is used to evaluate and compare the safety and efficacy of Tecres and radiopaque bone cement in experimental pigs, and to determine the puncture method suitable for pigs and the pre-clinical evaluation method for the safety and efficacy of bone cement. MethodsTwenty-four experimental pigs (with a body weight of 60-80 kg) were randomly divided into an experimental group (Group A) and a control group (Group B). Group A was the Tecres bone cement group, and Group B was the radiopaque bone cement group, with 12 pigs in each group. Under the monitoring of a C-arm X-ray machine, the materials were implanted into the 1st lumbar vertebra (L1) and 4th lumbar vertebra (L4) of the pigs via percutaneous puncture using the unilateral pedicle approach. The animals were euthanized at 4 weeks and 26 weeks after the operation, respectively. The L4 vertebrae were taken for compressive strength testing, and the L1 vertebrae were taken for hard tissue pathological examination to observe the inflammatory response, bone necrosis, and degree of osseointegration at the implantation site. ResultsThe test results of compressive strength between groups A and B showed no significant difference at 4 weeks and 26 weeks after bone cement implantation (P > 0.05). Observation under an optical microscope (×100) revealed that at 4 weeks postoperatively, both groups A and B showed that the bone cement was surrounded by proliferative fibrous tissue, with lymphocyte infiltration around it. The bone cement was combined with bone tissue, the trabecular arrangement was disordered, and osteoblasts and a small amount of osteoid were formed. At 26 weeks postoperatively, bone cement was visible in both groups A and B. The new bone tissue was mineralized, the trabeculae were fused, the trabecular structure was regular and dense with good continuity, and no obvious inflammatory reaction was observed. ConclusionIn experimental pig vertebrae, there were no significant differences observed in the compressive strength, inflammation response, bone destruction, and integration with the bone between Tecres and non-radiopaque bone cement. Both exhibited good biocompatibility and osteogenic properties. It indicates that using vertebroplasty to evaluate the safety and efficacy of bone cement in pigs is scientifically sound.

Objective To investigate the impact of blood sampling from different sites on coagula-tion results during systemic heparin anticoagulation period treated by continuous renal replacement therapy(CRRT).Methods Seventy-eight patients undergoing CRRT with systemic heparin anticoag-ulation were selected.Using a self-control method,blood samples were simultaneously collected from sampling port at input end of the CRRT extracorporeal circuit,the arterial pressure monitoring cathe-ter,and the peripheral vein of the patients.The four coagulation parameters were tested,and the differences in coagulation results among the blood sampling sites were compared.Results During CRRT with systemic heparin anticoagulation,the four coagulation parameters using blood samples col-lected from the sampling port at the input end of the CRRT extracorporeal circuit,the arterial pressure monitoring catheter,and the peripheral vein showed no statistically significant differences(P＞0.05).Subgroup analyses based on different hemofiltration machines and heparin doses also showed no statisti-cally significant differences(P＞0.05).Conclusion During CRRT,blood sampling from the sam-pling port at the input end of the circuit or the arterial pressure monitoring catheter can be used as an alternative to peripheral venous blood sampling,with no impact on coagulation results.

Objective To prepare glucose transporter 1(Glut1)-targeted doxorubicin(DOX)-loaded liposomes(doxorubicin/polyphyllin H-liposomes,DOX/ppH-LPs)using polyphyllin H(ppH)instead of cholesterol as the liposomal membrane material,and to investigate their in vitro synergistic anti-tumor activity against non-small cell lung cancer(NSCLC).Methods DOX/ppH-LPs were prepared using thin-film hydration,and the formulation was optimized by single-factor investigation.The optimized DOX/ppH-LPs were characterized for morphology,particle size,polydispersity index(PDI),and zeta potential with transmission electron microscopy(TEM)and dynamic light scattering(DLS).Drug loading DL%was determined by high-performance liquid chromatography(HPLC).The storage stability was evaluated by observing in PBS at 4℃for 7 d,and the serum stability was observed in DMEM containing 10%fetal bovine serum(FBS)at 37℃for 48 h.In vitro drug release was studied in PBS at pH 7.4 and pH 5.0 values,respectively.Human NSCLC A549 cells were subjected as the model,MTT assay was performed to detect the proliferation inhibition by DOX/ppH-LPs at different concentrations(0.5,5.0,15.0 μg/mL)and the control group(ppH+DOX/LPs,a physical mixture of free ppH and DOX-loaded liposomes).Fluorescence microscopy was used to observe cellular uptake of DOX/ppH-LPs and DOX/LPs(containing 5 μg/mL DOX)at 15 min and 2 h.Live/dead cell staining was applied to assess apoptosis/necrosis induced by formulations(15 μg/mL DOX)after 48 h incubation.Transwell assay was conducted to evaluate inhibitory effect on cell migration and invasion,and the targeting property and in vitro synergistic anti-NSCLC activity of DOX/ppH-LPs were then comprehensively evaluated.Results The optimal formulation of DOX/ppH-LPs was determined as hydration temperature at 50℃,6 mg DOX,2 mg ppH,and 24 mg lecithin.The prepared DOX/ppH-LPs were in spherical shape,uniform distribution,and at an average particle size of 145.13±22.14 nm,a PDI of 0.15±0.05,a zeta potential of-23.92±1.73 mV,and a DL of 10.13±0.71%for DOX and(1.22±0.21)%for ppH.DOX/ppH-LPs maintained stable particle size,PDI,and exhibited significantly unchanged zeta potential after storage in PBS at 4℃for 7 d or incubation in DMEM containing 10%FBS at 37℃for 48 h,demonstrating excellent physical and serum stability.Both liposomes showed slow release at pH 7.4 value,while drug release was significantly accelerated at pH 5.0 value(P<0.05),indicating pH-sensitive release characteristics.MTT assay revealed that DOX/ppH-LPs exerted significantly stronger cytotoxicity against A549 cells than the ppH+DOX/LPs control group(P<0.05).Compared with ppH+DOX/LPs,DOX/ppH-LPs showed remarkably enhanced cellular uptake in A549 cells(P<0.05),with more DOX localized in the nucleus.Live/dead cell staining showed that at the same DOX concentration(15 μg/mL),the proportion of apoptotic/necrotic cells induced by DOX/ppH-LPs was significantly higher than that of the DOX/LPs control group.Transwell assay demonstrated that there were significantly less cells migrating and invading through the membrane in the DOX/ppH-LPs group than the ppH+DOX/LPs group.Conclusion Glut1-targeted doxorubicin-loaded liposomes(DOX/ppH-LPs)constructed by substituting cholesterol with ppH can target NSCLC cells,significantly enhance the in vitro synergistic anti-NSCLC activity of DOX and ppH.

BACKGROUND:Preliminary clinical observations found that Jiawei Chunze Decoction is an effective formula for clinical treatment of urinary retention after spinal cord injury.Animal experiments have found that the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway is closely related to the degree of bladder dysfunction. OBJECTIVE:To further investigate the effects of Jiawei Chunze Decoction on bladder function and PI3K/Akt signaling pathway in rats with urinary retention. METHODS:Sixty female Sprague-Dawley rats were randomly divided into sham operation group,model group,Jiawei Chunze Decoction low-dose group,Jiawei Chunze Decoction high-dose group and agonist group.In the sham operation group,the spinal cord was exposed but not transected.In the other groups,the modified Hassan Shaker spinal cord transection method was used to prepare the model of sacral medullary injury.At 24 hours after modeling,the sham operation group and model group were intragastrically given equal volume of normal saline,Jiawei Chunze Decoction low-dose and high-dose groups were given Jiawei Chunze Decoction granules containing 14.4 and 28.8 g/kg,respectively,via intragastric administration for 4 weeks,and the agonist group was treated with an intraperitoneal injection of PI3K/Akt signaling pathway agonist 740Y-P at a dose of 0.02 mg/kg.After 4 weeks of treatment,the maximum bladder capacity,leakage point pressure and bladder compliance of rats in each group were detected by urine flow dynamics.The minimum bladder contraction tension and frequency of rats in each group were detected by detrusor pull test.The pathological changes of the rat bladder in each group were observed by hematoxylin-eosin staining.The concentrations of GRP78,CHOP and Caspase-12 in serum were detected by ELISA,and the mRNA and protein expressions of PI3K,Akt,GRP78,CHOP and Caspase-12 in bladder tissues were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the sham operation group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats in the model group were increased(P<0.05),and the leakage point pressure and bladder contraction frequency were decreased(P<0.05);serum GRP78,CHOP,and Caspase-12 levels were also increased(P<0.05).The arrangement of bladder epithelial cells in the model group was disordered,and there was monocyte infiltration between cells,tissue edema,and detrusor tract atrophy.The mRNA and protein expressions of PI3K and Akt in bladder tissues were significantly decreased in the model group compared with the sham operation group,while those of GRP78,CHOP and Caspase-12 were increased(P<0.05).Compared with the model group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats were decreased in the Jiawei Chunze Decoction low-dose,high-dose and agonist groups after 4 weeks of intervention(P<0.05),while the leakage point pressure and bladder contraction frequency were increased(P<0.05);serum GRP78,CHOP,Caspase-12 levels were decreased(P<0.05).The bladder epithelial cells in the three intervention groups were distributed evenly,arranged neatly,with less inflammatory cell infiltration and fuller detrusor muscle bundle.Compared with the model group,the mRNA and protein expressions of PI3K and Akt were increased in the three intervention groups,while those of GRP78,CHOP and Caspase-12 were decreased(P<0.05).The Jiawei Chunze Decoction high-dose group was better than the Jiawei Chunze Decoction low-dose group and shared the similar results with the agonist group.To conclude,Jiawei Chunze Decoction can improve the bladder function of rats with urinary retention after spinal cord injury,and the mechanism may be related to reducing the occurrence of endoplasmic reticulum stress in bladder tissue through the PI3K/Akt signaling pathway,and then alleviating apoptosis.

Under the trend of increasing aging， integrated elderly care and medical services is an important measure to optimize the supply of elderly care services and promote the good death of the elderly. Using the cooperative production theory and the classical grounded theory， a qualitative analysis was conducted on 38 cases of elderly palliative care and 25 cases of hospital-based palliative care under the integrated elderly care and medical services model from a hospital in Nanning City using Nvivo 20.0 software. This paper found that the integrated elderly care and medical services mode emphasized the deep integration of medical and elderly care services by integrating resources and improving service efficiency， to achieve the basic experience of comprehensive health care for the elderly. The promotion of these experiences has a positive significance for building a multi-agent cooperative production system， strengthening personnel training， perfecting the performance distribution mechanism， and further promoting the development of the national palliative care pilot.

BACKGROUND:Research has demonstrated a close association between ferroptosis and vascular dementia.Tongmai Kaiqiao Pill has a certain effect on improving the cognitive function of vascular dementia patients,but its mechanism is unclear. OBJECTIVE:To explore the interventional effects and molecular mechanisms of Tongmai Kaiqiao Pill for vascular dementia based on the regulation of ferroptosis by the nuclear factor erythroid-2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4)signaling pathway. METHODS:Among eighty-four SD male rats,12 rats were used as the sham-operated group,and the rest of them were prepared as a model of vascular dementia by the modified 2-VO method,and then randomly divided into the model group,the Tongmai Kaiqiao Pills high-,moderate-,and low-dosage(27.6,13.8,and 6.9 g/kg)groups,the combined group(Tongmai Kaiqiao Pill high-dosage+ML385,20 mg/kg),and the donepezil hydrochloride group(0.45 mg/kg).The drug was given once a day by intragastric administration.The combined group was also intraperitoneally injected Nrf2 inhibitor ML385,once a day,for 4 weeks.Morris water maze was used to detect the learning memory ability of rats.Hematoxylin-eosin staining was used to observe the histopathological changes in the hippocampus of rats in each group.Colorimetric assay was used to detect the content of reduced glutathione,ferrous ion(Fe2+),and malondialdehyde in the serum of rats.Prussian blue staining was used to detect the iron deposition in the hippocampal tissue of rats.Transmission electron microscopy was used to observe the ultrastructural changes of mitochondria in rat hippocampal tissues.Western blot assay was used to detect the protein expression levels of Nrf2,HO-1,GPX4,XCT,and ferritin heavy chain 1(FTH1)in rat hippocampal tissues. RESULTS AND CONCLUSION:(1)In comparison to the sham operation,rats in the model group exhibited a significantly prolonged latency period(P<0.05)and a reduced number of platform crossings(P<0.05).Additionally,the hippocampal tissues of these rats displayed loosely organized structure,deeply stained cell nuclei,and solidified or lysed chromatin.Ferri ions aggregated in CA1 region.There were atrophied mitochondria with dissolved cristae and thickened mitochondrial membranes.Fe2+,malondialdehyde,and reduced glutathione levels in rat serum were found to be elevated(P<0.05).A significant reduction in the expression of GPX4,HO-1,XCT,Nrf2,and FTH1 proteins was detected in the hippocampus(P<0.05).(2)Compared to the model group,the average escape latency of the rats was significantly reduced following intervention with Tongmai Kaiqiao Pills and donepezil hydrochloride(P<0.05),with an increased number of platform crossings(P<0.05).Hippocampal neurons showed significant recovery.Notably,iron aggregation in the CA1 region was significantly reduced,and mitochondrial structure and function were improved.There were significant reductions in Fe2+and malondialdehyde levels,while the levels of GPX4,HO-1,XCT,Nrf2,and FTH1 in rat hippocampal tissues,and reduced glutathione in serum were significantly increased(P<0.05).(3)The high-dose Tongmai Kaiqiao Pills exhibited a treatment effect comparable to that of donepezil hydrochloride(P>0.05),with a significant prolongation of water maze escape latency(P<0.05),a reduced number of platform crossings(P<0.05),and insignificant neuronal pathological changes in the CA1 area.However,the combined group showed increased iron deposition,elevated malondialdehyde and Fe2+levels in blood serum(P<0.05),reduced glutathione content(P<0.05),hippocampal tissue mitochondrial atrophy,and reduced expression of Nrf2,XCT,HO-1,GPX4,and FTH1 proteins(P<0.05).Within a certain range,higher doses of Tongmai Kaiqiao Pills demonstrated a more pronounced effect,comparable to the efficacy of high-dose donepezil hydrochloride.(4)It is concluded that Tongmai Kaiqiao Pills have been shown to mitigate histopathological changes in the rat hippocampus and enhance cognitive function in rats with vascular dementia.The mechanism of action is likely associated with the suppression of ferroptosis through the activation of the Nrf2/HO-1/GPX4 signaling pathway.

Purpose To develop a nomogram combined radiomics,clinical and CT morphographic features for the prediction of the acquired T790M mutation in patients with advanced non-small cell lung cancer with resistance after the duration of first-line epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitor(TKI)treatment.Materials and Methods The chest CT images and clinical data of 116 patients who underwent secondary biopsy after disease progression during first-line TKI treatment for advanced non-small cell lung cancer with EGFR sensitive mutations,from December 2016 to December 2022 in Shaoxing People's Hospital were retrospectively analyzed.All patients were randomly divided into a training cohort(n=81)and a validation cohort(n=35),at a ratio of 7︰3.The regions of interest of the lesion were delineated,and radiomics features were extracted.Feature selection was performed via the maximum relevance minimum redundancy and the least absolute shrinkage and selection operator methods.Clinical features were selected via univariate and multivariate Logistic regression.A nomogram combined clinical and radiomics features was subsequently constructed.The predictive ability of the combined model was evaluated via receiver operator characteristic curve,calibration curves and decision curve analysis.Results The progression-free survival of first-line EGFR-TKIs(OR=1.086,P=0.041),initial EGFR profile(OR=0.280,P=0.021),vascular convergence(OR=4.050,P=0.036)and air bronchogram(OR=3.265,P=0.030)were highly correlated with the acquired T790M mutation.The combined model demonstrated good predictive performance for acquired T790M mutation,both in the training set(AUC=0.867,95%CI 0.790-0.944)and the validation set(AUC=0.895,95%CI 0.786-1.000).The calibration curve showed good calibration power,and the decision curve analysis demonstrated a significant net benefit.Conclusion A radiomics-clinical nomogram based on CT radiomics has the potential to predict acquired T790M mutation and could be a complementary tool for T790M mutation detection after resistance to first-or second-generation EGFR-TKIs.