To address the constrains imposed by insufficient hydrogen peroxide (H2O2) and high glutathione (GSH) expression in tumor cells on the efficacy of chemodynamic therapy (CDT), zeolitic imidazolate framework-8 (ZIF-8) loaded with disulfiram (DSF) and 3-amino-1,2,4-triazole (3-AT) was synthesized via a one-pot approach. Subsequently, hyaluronic acid (HA)-modified cupric peroxide (CuO2) was in-situ grown on its surface through biomineralization to construct a multifunctional copper-based nanozyme ADZCH (3-AT/DSF@ZIF-8@CuO2-HA). This nanoplatform disrupts the intratumoral H2O2 homeostasis, depletes GSH, and synchronously delivers DSF and Cu2+ via cascade catalysis, thereby enhancing CDT and sensitizing tumors to DSF-based chemotherapy. The results of physicochemical characterization indicated that ADZCH presented a uniform core-shell structure with favorable dispersibility. Its particle size and Zeta potential were 196.5 nm and −19.5 mV, respectively. It possessed a microporous structure with a specific surface area of 81.8600 m2/g, and demonstrated efficient loading capacity for DSF and 3-AT, achieving drug loading efficiencies of 5.91% and 45.07%, respectively. Moreover, ADZCH can continuously and slowly release drugs in an acidic environment and maintain good stability under diverse physiological conditions. In vitro functional assays verified that ADZCH catalytically generated H2O2 and hydroxyl radicals while concurrently depleting GSH in a concentration- and incubation time-dependent manner. Cellular uptake experiments showed that HA modification significantly improved the uptake of nanoparticles by 4T1 cells. Cytotoxicity tests showed that 80 μg/mL ADZCH had a significant cytotoxic effect on 4T1 cells but no significant toxicity on L929 cells. DCFH-DA probe detection indicated that ADZCH could significantly induce intracellular reactive oxygen species (ROS) generation, thereby enhancing CDT efficacy. Live/dead staining experiments showed that ADZCH efficiently induced apoptosis, with the proportion of dead cells reaching 94.74%, demonstrating its promising potential for anti-tumor applications.This study provides new research ideas and experimental basis for overcoming the tumor microenvironment barrier and enhancing the anti-tumor effect of CDT combined with chemotherapy.

Objective:To observe the effect of combining heat-sensitive moxibustion with action observation therapy in the treatment of spastic wrist and hand dysfunction post-stroke.Methods:Ninety stroke survivors with spasmodic wrist and hand dysfunction were randomly assigned to a heat-sensitive moxibustion group, an action observation group, or a combination group, each of 30. In addition to routine rehabilitation treatment, the groups received heat-sensitive moxibustion, action observation therapy or moxibustion followed by action observation therapy in 6 sessions a week over 6 weeks. Surface electromyography signals (iEMG and RMS) were recorded from the affected wrist and hand muscles before and after the treatment. All of the participants were also assessed using the Fugl-Meyer motor assessment for the upper extremities (FMA-UE).Results:After treatment, a significant improvement was observed in the average FMA-UE values, with that of the combination group (17.2±2.1) significantly higher than those of the other two groups. The average iEMG of the wrist flexors and extensors, the extensors of the fingers, and abductor pollicis brevis had increased significantly, with the combination group′s averages significantly higher than those of the other two groups. The average RMS values of those muscles had decreased significantly after the treatment, with those of the combination group significantly lower than the others.Conclusions:Combining heat-sensitive moxibustion and action observation therapy can significantly reduce muscle tension, and promote strength and better functioning of spastic wrist and hand muscles after a stroke. The combination is worthy of clinical application and promotion.

Objective:To establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of N-desalkylquetiapine, hydroxybupropion, N-desmethyl clozapine, N-desmethyl clomipramine, O-desmethyvenlafaxine and dehydro aripiprazole in human plasma.Methods:In June 2023, plasma samples were treated with methanol-acetonitrile (volume ratio of 1∶1) for protein precipitation and then detected by LC-MS/MS. It was separated by C18 column and eluted with 5 mmol/L ammonium acetate water and 5 mmol/L ammonium acetate methanol solution as mobile phase gradient. The metabolites of six psychotropic drugs were qualitatively and quantitatively by using electrospray positive ion multi-reactive ion monitoring scanning mode (MRM) .Results:The linear relationships of six psychotropic drug metabolites were good in the concentration range of 2-100 μg/L. The linear correlation coefficients were 0.9971-0.9999, the limits of quantification of the method were 0.10-6.00 μg/L, and the inter-and intra-day precision were 4.6%-9.8% and 1.5%-8.6%, with the recoveries of the spiked standards ranged from 90.0% to 106.1%.Conclusion:The LC-MS/MS method for the determination of metabolites of six psychotropic drugs in human plasma is simple, rapid and sensitive, and can be used for the qualitative and quantitative determination of metabolites in plasma samples of patients suspected of psychotropic drug poisoning.

Objective:To establish a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the fast determination of maduramicin ammonium (MAD) in rat serum.Methods:In February 2024, rat serum samples were selected and directly injected after extraction and purification with methanol: acetonitrile (1: 1), separated on a C18 chromatographic column, and gradient-eluted using 0.1% formic acid aqueous solution -0.1% formic acid methanol solution as the mobile phase. Under optimized instrument conditions, electrospray positive ion multiple reaction monitoring (MRM) mode was employed for quantification using the external standard method, followed by methodological validation of the established approach.Results:The linearity of MAD in serum was good in the concentration range of 0.5-100 μg/L, and the correlation coefficient was 0.9997. The mean recoveries of MAD from spiked samples were 86.0%-109.6%, with the relative standard deviations were less than 10%. The limit of detection was 0.23 μg/L, The limit of detection was 0.75 μg/L.Conclusion:This method is high sensitive and reliable, which is suitable for the determination of MAD in in mouse serum.

Objective:To explore the correlation between serum uric acid/high-density lipoprotein cholesterol ratio (UHR) and the risk of hypertension in elderly physical examination populations.Methods:This study was a cross-sectional study. A total of 1 028 patients aged≥60 years who underwent physical examinations at the Health Management Center of Fuwai Central China Cardiovascular Hospital from September 2023 to February 2024 were included in this study. The general demographic data, past medical history, physical examination and laboratory examination indicators of the physical examiners were collected, and according to whether they had hypertension or not, they were divided into hypertension group (390 cases) and non-hypertension group (638 cases), and all UHR values were arranged from small to large, and the UHR was divided into three groups by tertiles of UHR, and the general data and blood biochemical indexes between the groups were compared. Spearman rank correlation was used to analyze the correlation between UHR level and body mass index, total cholesterol, triglyceride and other indexes in the elderly population. Logistic regression was used to explore the relationship between UHR level and hypertension in the elderly population, and the stratification analysis of the physical examination population was carried out according to diabetes, coronary heart disease and dyslipidemia, and the interaction test between groups was carried out.Results:Among the 1 028 geriatric physical examination cases, 580 (56.4%) were males and 448 (43.6%) were females, aged (66.7±5.8) years. UHR levels were higher in the hypertensive group compared to the non-hypertensive group [248.88 (191.19, 322.25) vs 213.52 (165.94, 275.29); Z=-5.445, P<0.05]. With the increase of UHR level, the detection rate of hypertension in the elderly population increased (accounted for 27.8%, 38.2% and 47.8%, respectively; χ2=29.211, P<0.05). Spearman rank correlation analysis showed that UHR was positively correlated with body mass index, triglycerides, serum uric acid, serum creatinine and fasting blood glucose ( r=0.318, 0.334, 0.774, 0.474, 0.080; all P<0.05), and negatively correlated with total cholesterol, glomerular filtration rate and low-density lipoprotein cholesterol ( r=-0.239, -0.303, -0.154; all P<0.05). When the confounding factors were not adjusted (model 1), the risk of hypertension in high UHR group was 2.382 times higher than that in low UHR group and 1.607 times higher than that in medium UHR group; after adjusting for all confounding factors such as age, gender, body mass index, systolic blood pressure, diastolic blood pressure, junior high school education or below, smoking, alcohol consumption, glomerular filtration rate, etc., the risk of hypertension in the high-level UHR group was 1.732 times higher than that in the low-level UHR group (95% CI: 1.139-2.635) ( P<0.05). The elderly physical examination population was further stratified according to whether there was diabetes, dyslipidemia and coronary heart disease, and it was found that there was no interaction between UHR and diabetes, dyslipidemia and coronary heart disease on the prevalence of hypertension (all P>0.05). Conclusions:Hypertension detection rate increases with higher UHR levels. UHR is closely related to the incidence of hypertension in the elderly population.

Tumor-associated macrophages(TAM)are a current focus in the study of the tumor microenvironment.To achieve their functionally distinct roles,macrophages undergo phenotypic polarization resulting in two major subgroups:M1 macrophages with pro-inflammatory and anti-tumor effects,and M2 macrophages with anti-inflammatory and pro-tumor effects.Of these,M2 polarization,as the main manifestation of TAMs,has been associated with a poor prognosis in various cancers and has been shown to support malignancies.Gastric carcinoma has a low early-diagnosis rate,late disease stage,and poor prognosis,with biological behavioral characteristics of easy recurrence and metastasis.Drug resistance and toxic side effects currently limit the application and effectiveness of treatments,and there is thus an urgent need to explore new therapeutic drugs and targets.This review summarizes recent progress in studies of TAM in relation to the occurrence,development,and drug resistance of gastric carcinoma,providing new ideas for clinical treatment and prognosis prediction in patients with gastric carcinoma.

Objective:To establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of N-desalkylquetiapine, hydroxybupropion, N-desmethyl clozapine, N-desmethyl clomipramine, O-desmethyvenlafaxine and dehydro aripiprazole in human plasma.Methods:In June 2023, plasma samples were treated with methanol-acetonitrile (volume ratio of 1∶1) for protein precipitation and then detected by LC-MS/MS. It was separated by C18 column and eluted with 5 mmol/L ammonium acetate water and 5 mmol/L ammonium acetate methanol solution as mobile phase gradient. The metabolites of six psychotropic drugs were qualitatively and quantitatively by using electrospray positive ion multi-reactive ion monitoring scanning mode (MRM) .Results:The linear relationships of six psychotropic drug metabolites were good in the concentration range of 2-100 μg/L. The linear correlation coefficients were 0.9971-0.9999, the limits of quantification of the method were 0.10-6.00 μg/L, and the inter-and intra-day precision were 4.6%-9.8% and 1.5%-8.6%, with the recoveries of the spiked standards ranged from 90.0% to 106.1%.Conclusion:The LC-MS/MS method for the determination of metabolites of six psychotropic drugs in human plasma is simple, rapid and sensitive, and can be used for the qualitative and quantitative determination of metabolites in plasma samples of patients suspected of psychotropic drug poisoning.

Objective:To establish a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the fast determination of maduramicin ammonium (MAD) in rat serum.Methods:In February 2024, rat serum samples were selected and directly injected after extraction and purification with methanol: acetonitrile (1: 1), separated on a C18 chromatographic column, and gradient-eluted using 0.1% formic acid aqueous solution -0.1% formic acid methanol solution as the mobile phase. Under optimized instrument conditions, electrospray positive ion multiple reaction monitoring (MRM) mode was employed for quantification using the external standard method, followed by methodological validation of the established approach.Results:The linearity of MAD in serum was good in the concentration range of 0.5-100 μg/L, and the correlation coefficient was 0.9997. The mean recoveries of MAD from spiked samples were 86.0%-109.6%, with the relative standard deviations were less than 10%. The limit of detection was 0.23 μg/L, The limit of detection was 0.75 μg/L.Conclusion:This method is high sensitive and reliable, which is suitable for the determination of MAD in in mouse serum.

Objective:To explore the effect of specific inhibitor of Smad3 (SIS3) on glucocorticoid-induced ocular hypertension in mice and its possible mechanism.Methods:Fifty-one eight-week-old female C57BL/6J mice were randomly divided into control group, dexamethasone group and SIS3 group by the random number table method, with 17 mice in each group.Mice in the control group were injected with 20 μl 2 % polyvinyl alcohol into the conjunctival fornix every week for 4 weeks.Mice in the dexamethasone group and SIS3 group were injected with 20 μl 10 mg/ml dexamethasone acetate every week and SIS3 group was treated with additional 100 μg/ml SIS3 nanomicelle eye drops 3 times daily for up to 4 weeks.Intraocular pressure (IOP) was measured weekly using Icare rebound tonometer.Mice were sacrificed 4 weeks after treatment, and the eyeballs were removed.Morphology of trabecular meshwork (TM) tissues were detected by hematoxylin-eosin (HE) staining.The collagen deposition area in TM tissues were examined by Masson staining.Fibronectin (FN) and collagen type Ⅰ (Col-1) in the extracellular matrix of TM tissue were detected by immunofluorescence staining.TM tissues were obtained from donated patients, and primary human trabecular meshwork cells (HTMCs) were obtained by culture.The expression level of myocilin in dexamethasone-induced HTMCs was detected by immunofluorescence and Western blot for cell identification.Primary HTMCs were divided into normal control group, dexamethasone group and SIS3 group cultured with normal culture medium, medium containing 400 nmol/L dexamethasone, medium containing 400 nmol/L dexamethasone+ 10 μmol/L SIS3 for 48 hours, respectively.The expression levels of FN, Col-1 and p-Smad3/Smad3 proteins were measured by Western blot.The use and care of animals complied with the ARVO statement.This study protocol was approved by the Animal Ethics Committee of Zhengzhou University (No.ZZU-LA20220729).The collection of TM tissue specimens complied with the Declaration of Helsinki and was approved by the Medical Ethics Committee of Henan Provincial Eye Hospital (No.HNEECKY-2022[18]).The patients knew the purpose of the experiment and signed the informed consent forms.Results:There was a significant overall difference in IOP among the three groups at different time points after administration ( Fgroup=72.94, P<0.001; Ftime=33.19, P<0.001).Compared with baseline, IOP was increased in the dexamethasone group at each time point after administration, and the differences were statistically significant (all P<0.001).The IOP of the control and SIS3 groups at weeks 1, 2, 3, 4 were significantly lower than that of the dexamethasone group (all P<0.001).HE staining showed that the iridocorneal angles of all groups were open with similar morphology of the TM structure.Masson staining showed that the positive expression area of collagen in the control group, dexamethasone group and SIS3 group was (9.57±2.91)%, (27.75±5.88)% and (11.67±3.78)%, respectively, with a statistically significant difference among the three groups ( F=25.91, P<0.001), and the positive expression area of collagen was significantly lower in the control group and SIS3 group than in the dexamethasone group (all P<0.001).The fluorescence expression level of FN in the control group, dexamethasone group and SIS3 group was 8.00±1.92, 14.01±2.74 and 7.85±0.64, respectively, and the fluorescence expression level of Col-1 was 6.90±1.16, 14.36±3.19 and 4.90±0.88, respectively, with statistically significant differences among the three groups ( F=15.93, 30.29; both P<0.001), and the fluorescence expression levels of FN and Col-1 were significantly lower in the control group and SIS3 group than in the dexamethasone group (all P<0.01).Immunofluorescence staining and Western blot showed that the cultured primary cells expressed myocilin and the expression level of myocilin was significantly increased after dexamethasone induction, which was identified as HTMCs.There were statistically significant differences in the relative expression levels of FN, Col-1, and p-Smad3/Smad3 proteins among different groups of cells ( F=8.22, 23.08, 8.78; all P<0.05), and the relative expression levels of FN, Col-1, and p-Smad3/Smad3 proteins were significantly lower in the control group and SIS3 group than in the dexamethasone group (all P<0.05). Conclusions:SIS3 reduces IOP by inhibiting p-Smad3, reducing extracellular matrix deposition in TM, and reducing fibrosis in the TM tissue.

Tumor-associated macrophages(TAM)are a current focus in the study of the tumor microenvironment.To achieve their functionally distinct roles,macrophages undergo phenotypic polarization resulting in two major subgroups:M1 macrophages with pro-inflammatory and anti-tumor effects,and M2 macrophages with anti-inflammatory and pro-tumor effects.Of these,M2 polarization,as the main manifestation of TAMs,has been associated with a poor prognosis in various cancers and has been shown to support malignancies.Gastric carcinoma has a low early-diagnosis rate,late disease stage,and poor prognosis,with biological behavioral characteristics of easy recurrence and metastasis.Drug resistance and toxic side effects currently limit the application and effectiveness of treatments,and there is thus an urgent need to explore new therapeutic drugs and targets.This review summarizes recent progress in studies of TAM in relation to the occurrence,development,and drug resistance of gastric carcinoma,providing new ideas for clinical treatment and prognosis prediction in patients with gastric carcinoma.