The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

ObjectiveTo develop a nomogram-based risk prediction model for chronic obstructive pulmonary disease (COPD) incidence among the community-dwelling population aged 40 years old and above, so as to provide targeted references for the screening and prevention of COPD. MethodsBased on a natural population cohort in suburban Shanghai, a total of 3 381 randomly selected participants aged ≥40 years underwent pulmonary function tests between July and October 2021. Cox stepwise regression analysis was used to develop overall and gender-specific risk prediction models, along with the construction of corresponding risk nomograms. Model predictive performance was evaluated using the C-indice, area under the curve (AUC) values, and Brier score. Stability was assessed through 10-fold cross-validation and sensitivity analysis. ResultsA total of 3 019 participants were included, with a median follow-up duration of 4.6 years. The COPD incidence density was 17.22 per 1 000 person-years, significantly higher in males (32.04/1 000 person-years) than that in females (7.38/1 000 person-years) (P<0.001). The overall risk prediction model included the variables such as gender, age, education level, BMI, smoking, passive smoking, and respiratory comorbidities. The male-specific model incorporated the variables such as age, BMI, respiratory comorbidities, and smoking, while the female-specific model included age, marital status, respiratory comorbidities, and pulmonary tuberculosis history. The C-indices for the overall, male-specific, and female-specific models were 0.829, 0.749, and 0.807, respectively. The 5-year AUC values were 0.785, 0.658, and 0.811, with Brier scores of 0.103, 0.176, and 0.059, respectively. Both 10-fold cross-validated C-indices and sensitivity analysis (excluding participants with a follow-up duration of <6 months) yielded C-indices were above 0.740. ConclusionThis study developed concise and practical overall and gender-specific COPD risk prediction models and corresponding nomograms. The models demonstrated robust performance in predicting COPD incidence, providing a valuable reference for identifying high-risk populations and formulating targeted screening and personalized management strategies.

Objective To investigate the changes of serum metabolites in patients with occupational chronic lead poisoning using non-targeted metabolomics, and to screen differential metabolic pathways. Methods A total of 14 patients with occupational chronic lead poisoning were selected as the poisoning group, and 14 healthy people without occupational hazard exposure history were selected as the control group using the judgment sampling method. Serum of the individuals from the two groups was collected. Non-targeted metabolomics technology based on ultra high performance liquid chromatography-tandem mass spectrometry was used to detect serum metabolite levels in the two groups. Differential metabolites (DMs) were screened by the principal component analysis, partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis, and related metabolic pathways were explored. Results The blood lead level in the poisoning group was higher than that in the control group (median: 359.59 vs 5.04 μg/L, P<0.01). There were significant differences in serum metabolites between the poisoning group and control group. After the combination of results from the positive and negative ion patterns, a total of 89 DMs were screened in serum of patients in the poisoning group, including 50 upregulated and 39 downregulated metabolites compared with the control group. The serum DMs of poisoning group were mainly enriched in arginine biosynthesis, ABC transporter, purine metabolism, choline metabolism in malignant tumor, glycerophospholipid metabolism and ether lipid metabolism compared with the control group (all P<0.05). Conclusion Abnormal changes of serum metabolic profile occurred in patients with occupational chronic lead poisoning. The metabolic pathways such as arginine biosynthesis, ABC transporter, purine metabolism, choline metabolism, glycerophospholipid metabolism and ether lipid metabolism may be involved in the occurrence and development of lead poisoning.

Objective:To construct an evaluation system for clinical thinking ability of general practitioners in the treatment of multimorbidity.Methods:This was a cross-sectional study. The draft of evaluation indexes for clinical thinking ability of general practitioners in treatment of multimorbidity was preliminary developed through literature review, collation, analysis and discussion. Nineteen clinical and teaching experts of general practice were selected for consultation via anonymous convenient sampling. From January to June 2022, 2 rounds of expert consultation were conducted using the Delphi method. During the first round of consultation, according to the survey feedback, we modified and improved the evaluation system of general practitioners′ clinical thinking ability for multi-disease co-treatment. During the second round, experts were asked to assess the importance of each index, and to calculate the weight of each index accordingly. Questionnaires were sent to experts via letters. The content of the questionnaires encompasses the basic information of experts, evaluation for various indexes and relevant opinions. The mean value of importance assignment ≥3.5, coefficient of variation ≤0.25 and the full score frequency ≥30% were taken as the criteria. Indexes unsatisfying the criteria were removed, so that the final index system could be constructed.Results:The average age of 19 experts was 50.2 years old, 9 of them were male. A total of 2 rounds of expert consultation were conducted, 19 questionnaires were issued in each round, and 19 effective questionnaires were received afterwards. In the first round of consultation, 10 experts put forward revised opinions, and some indexes were adjusted according to the definition criteria and the discussion of the research group. In the second round of consultation, 3 experts put forward suggestions for modification. According to the definition criteria, no need to delete the indexes. After discussion by the research group, some indexes were adjusted, and finally an evaluation system of clinical thinking ability for multi-disease co-treatment of general practitioners was established, including 4 first-level indexes and 30 second-level indexes. The weights of the 4 first-level indexes in descending order were "overall thinking ability" (38.01%), "diagnostic thinking ability" (33.96%), "evidence-based thinking ability" (14.75%), and "critical thinking ability" (13.28%). Among the 30 secondary indexes, the top 5 were "ability to identify and handle priority emergency incidents" (5.04%), "risk assessment and critical illness identification ability" (4.63%), "emergency referral ability" (4.61%), "communication and expression ability" (4.57%), and "standardized diagnosis and treatment ability" (4.23%).Conclusion:This study successfully constructed an evaluation system for clinical thinking ability of general practitioners in the treatment of multimorbidity.

OBJECTIVE To investigate the effect of Banxia Xiexin decoction(BXD) on colitis associated cancer(CAC) mice and its related mechanism. METHODS Seventy-five C57BL/6 mice were randomly divided into normal group, model group, Banxia Xiexin decoction low-dose group, high-dose group and mesalazine group. Except for the normal group, the mice in the other groups were intraperitoneally injected with azoxymethane combined with oral dextran sodium sulfate to establish the CAC model. BXD and mesalazine were given respectively for intervention. The general conditions of all mice were observed and recorded, and the changes of body weight, disease activity index, colon length and tumor number were monitored. HE staining was utilized to observe the pathological changes of colon tissue. The expression levels of PCNA, NF-κB P65 and IκB-α were detected by immunohistochemistry. The mRNA levels of IL-17A, N-cadherin, E-cadherin and Bcl-2 were detected by qRT-PCR. Macrophage infiltration was measured using immunostaining analysis. Western blotting was applied to analyze the expression of NF-κB, E-cadherin and N-cadherin proteins in colon tissues of each group. RESULTS There was no significant tumor occurrence in the normal group, while the body weight of the model group mice was significantly reduced and the number of colon tumors increased. The colon length, number of tumors, and degree of inflammatory cell infiltration in the BXD group were significantly improved compared to the model group. Immunohistochemical results showed that the expression of PCNA, NF-κB P65 and IκB-α protein in colon tissue of model group was remarkably increased (P<0.01). Immunofluorescence results showed that the number of F4/80, CD80 and CD206 positive macrophages in the colon tissue of the model group increased (P<0.05 or P<0.01). The results of RT-PCR demonstrated that the levels of IL-17A, N-cadherin and Bcl-2 mRNA in the colon tissue of the model group were significantly increased (P<0.01), while the level of E-cadherin mRNA was fundamentally decreased (P<0.01). Western blotting results displayed that the expression levels of NF-κB and N-cadherin protein in colon tissue of model group were up-regulated (P<0.01), while E-cadherin was significantly down-regulated (P<0.01). Compared with the model group, the changes of the above indexes in the BXD and mesalazine groups were ameliorated, with statistical differences (P<0.05 or P<0.01), and the changes in the BXD high-dose group were more significant. CONCLUSION BXD exhibits strong anti-inflammatory and anti-tumor benefits in CAC mice, inhibiting macrophage activation in colon tissue and promoting M2 polarization, while reducing the expression of tumor associated proteins PCNA and Bcl-2, and block the progression of EMT related proteins (E-cadherin and N-cadherin). The mechanism may connect to suppressing NF-κB P65 and IκB-α activation to regulate the NF-κB signaling pathway.

OBJECTIVE To investigate the effect of Banxia Xiexin decoction(BXD) on colitis associated cancer(CAC) mice and its related mechanism. METHODS Seventy-five C57BL/6 mice were randomly divided into normal group, model group, Banxia Xiexin decoction low-dose group, high-dose group and mesalazine group. Except for the normal group, the mice in the other groups were intraperitoneally injected with azoxymethane combined with oral dextran sodium sulfate to establish the CAC model. BXD and mesalazine were given respectively for intervention. The general conditions of all mice were observed and recorded, and the changes of body weight, disease activity index, colon length and tumor number were monitored. HE staining was utilized to observe the pathological changes of colon tissue. The expression levels of PCNA, NF-κB P65 and IκB-α were detected by immunohistochemistry. The mRNA levels of IL-17A, N-cadherin, E-cadherin and Bcl-2 were detected by qRT-PCR. Macrophage infiltration was measured using immunostaining analysis. Western blotting was applied to analyze the expression of NF-κB, E-cadherin and N-cadherin proteins in colon tissues of each group. RESULTS There was no significant tumor occurrence in the normal group, while the body weight of the model group mice was significantly reduced and the number of colon tumors increased. The colon length, number of tumors, and degree of inflammatory cell infiltration in the BXD group were significantly improved compared to the model group. Immunohistochemical results showed that the expression of PCNA, NF-κB P65 and IκB-α protein in colon tissue of model group was remarkably increased (P<0.01). Immunofluorescence results showed that the number of F4/80, CD80 and CD206 positive macrophages in the colon tissue of the model group increased (P<0.05 or P<0.01). The results of RT-PCR demonstrated that the levels of IL-17A, N-cadherin and Bcl-2 mRNA in the colon tissue of the model group were significantly increased (P<0.01), while the level of E-cadherin mRNA was fundamentally decreased (P<0.01). Western blotting results displayed that the expression levels of NF-κB and N-cadherin protein in colon tissue of model group were up-regulated (P<0.01), while E-cadherin was significantly down-regulated (P<0.01). Compared with the model group, the changes of the above indexes in the BXD and mesalazine groups were ameliorated, with statistical differences (P<0.05 or P<0.01), and the changes in the BXD high-dose group were more significant. CONCLUSION BXD exhibits strong anti-inflammatory and anti-tumor benefits in CAC mice, inhibiting macrophage activation in colon tissue and promoting M2 polarization, while reducing the expression of tumor associated proteins PCNA and Bcl-2, and block the progression of EMT related proteins (E-cadherin and N-cadherin). The mechanism may connect to suppressing NF-κB P65 and IκB-α activation to regulate the NF-κB signaling pathway.

Objective To investigate the effect of miR-142-3p on the apoptosis of rat pancreatic exocrine cell line AR42J by regulating Hmgb1.Methods AR42J cells were divided into blank group(blank),acute pancreatitis model group(AP,100 nmol/L cerulein for 24 h),and then transfected with miR-142-3p mimics,mimics NC,miR-142-3p inhibitor and inhibitor NC,respectively.The cells in the model group were recorded as miR-142-3p mimics group,mimics NC group,miR-142-3p inhibitor group and inhibitor NC.The expression of miR-142-3p in cells was detected by RT-qPCR.The protein expressions of HMGB1,caspase-3,Bax and Bcl-2 were detected by Western blot.Hoechst staining was used to determine cell apoptosis.The apoptosis rate of cells was detected by flow cytometry.The targeting relationship between miR-142-3p and Hmgb1 was determined by dual luciferase reporter gene assay.Results Compared with blank control group,the expression level of miR-142-3p in the AP group was significantly down-regulated(P＜0.01),the expression level of HMGB1 and caspase-3 proteins was up-regulated(P＜0.05),the expression level of Bax protein was significantly up-regulated(P＜0.01),the expression level of Bcl-2 protein was significantly decreased(P＜0.01)and the apoptosis rate increased significantly(P＜0.01).Compared with the mimics NC group,the level of miR-142-3p in the miR-142-3p mimics group was significantly up-regulated(P＜0.01),the expression of HMGB,caspase-3 and Bax proteins was significantly down-regulated(P＜0.01),the expression of Bcl-2 protein was up-regulated(P＜0.05),and the apoptosis rate decreased signifi-cantly(P＜0.01).Compared with inhibitor NC group,the expression level of miR-142-3p in miR-142-3p inhibitor group was down-regulated(P＜0.05),the expression levels of HMGB1,caspase-3 and Bax proteins were signifi-cantly up-regulated(P＜0.01),the expression level of Bcl-2 protein was decreased(P＜0.05)and the apoptosis rate increased significantly(P＜0.01).The dual luciferase reporter gene assay showed that Hmgb1 was the target gene of miR-142-3p.Conclusions 1)The expression of miR-142-3p was low in the model group.2)miR-142-3p can inhibit the apoptosis of AR42J cells by inhibiting the expression of Hmgb1.

Objective To investigate the effects of different concentrations of PPF on oxidative stress and apoptosis of PD model cells induced by MPP+.Methods The human neuroblastoma cell SH-SY5Y was induced by 1 mM MPP+ to establish PD cell model.In PPF treatment group,SH-SY5Y cells were stimulated with 10,20,40 and 80 μM PPF for 4 h before MPP+ induction.Cell counting kit-8(CCK-8)was performed to evaluate cell proliferation activity.H2DCF-DA fluorescent probe was used to detect ROS in cells.The levels of MDA and NADPH oxidase were analyzed by the kit.Western blot examined the protein expression of cytochrome c in mitochondria and cytoplasm,as well as the relative expression of Bcl-2,Bax and cleaved caspase-3 in SH-SY5Y cells.Apoptosis rate was analyzed by flow cytometry.Results MPP+ significantly inhibited the proliferation of SH-SY5Y cells(P<0.001),promoted the level of ROS(P<0.001),MDA(P<0.001),NADPH oxidase(P<0.01),cytochrome c in cytoplasm(P<0.01)and induced apoptosis(P<0.001)and the relative expression of pro-apoptosis protein Bax and cleaved caspase-3(P<0.01),reduced cytochrome c protein in mitochondria(P<0.01)and the relative expression of anti-apoptosis protein(P<0.01).PPF pretreatment alleviated the proliferation inhibition,oxidative stress and apoptosis promotion of SH-SY5Y cells induced by MPP+(P<0.001),and the effects of 40 μM and 80 μM on cells were more significant.Conclusion PPF pretreatment can alleviate the oxidative stress of SH-SY5Y cells induced by MMP+ and reduce apoptosis rate.

BACKGROUND:Current studies have confirmed that Ganoderma lucidum polysaccharides can promote nerve regeneration in neurodegeneration-related diseases.The occurrence of neurodegenerative diseases is closely related to mitochondrial dysfunction,but the role of Ganoderma lucidum polysaccharides on the regulation of apoptosis and mitochondrial function in neurodegenerative diseases is not yet clarified. OBJECTIVE:To explore the regulatory effects and mechanisms of Ganoderma lucidum polysaccharides on apoptosis and mitochondrial dysfunction in H2O2-induced SH-SY5Y cells. METHODS:SH-SY5Y cells were divided into three groups:control group,H2O2 group,and Ganoderma lucidum polysaccharides group.Cells in the control group were normally cultured.Cells in the H2O2 group were treated with 300 μmol/L H2O2 for 24 hours.In the Ganoderma lucidum polysaccharides group,the intervention with 300 μg/L Ganoderma lucidum polysaccharides was conducted first for 1-2 hours,followed by the addition of 300 μmol/L H2O2 for 24 hours.The mitochondrial membrane potential was detected by JC-1 kit.Apoptosis was detected by TUNEL staining kit.The activities of malondialdehyde and superoxide dismutase were detected by malondialdehyde test kit and superoxide dismutase test kit,respectively.The apoptosis and expression of mitochondrial dynamics-related proteins were detected by immunofluorescence staining and western blot assay. RESULTS AND CONCLUSION:(1)Compared with the control group,the mitochondrial membrane potential and superoxide dismutase activity were significantly reduced,as well as apoptotic rate and malondialdehyde levels were significantly increased in the H2O2 group(P<0.05).After treatment with Ganoderma lucidum polysaccharides,the membrane potential and superoxide dismutase activities were significantly increased,and apoptotic rate and malondialdehyde levels were significantly reduced compared with the H2O2 group(P<0.05).(2)The expression levels of pro-apoptotic proteins Bax and Caspase-3 were significantly increased,but the expression of anti-apoptotic protein Bcl-2 was significantly decreased in the H2O2 group compared with the control group(P<0.05).Compared with the H2O2 group,the levels of Bax and Caspase-3 were significantly decreased,but the expression of anti-apoptotic protein Bcl-2 was significantly increased in the Ganoderma lucidum polysaccharides group(P<0.05).(3)Compared with the control group,the expression of mitochondrial splitting proteins Fis1 and p-Drp1 was significantly increased,but the expression of mitochondrial fusion proteins OPA1,Mfn1,and Mfn2 was decreased in the H2O2 group(P<0.05).Compared with the H2O2 group,Fis1 and p-Drp1 expression was significantly reduced,but the expression levels of OPA1,Mfn1,and Mfn2 were significantly increased in the Ganoderma lucidum polysaccharides group(P<0.05).(4)The above results confirm that Ganoderma lucidum polysaccharides can attenuate H2O2-induced oxidative stress damage and apoptosis in SH-SY5Y cells by ameliorating mitochondrial dysfunction.

Objective To establish an HPLC-based method for the determination of α-obscurine,ferulic acid,hydroxysafflower yellow A,benzoylneaconitine,benzoylaconitine,periplosin,4-methoxysalicylsalicylate,kaempferol and oleanolic acid simultaneously in Shujin Tongluo Black Plaster.Methods HPLC method was used to determine the 9 components in Shujin Tongluo Black Plaster simultaneously.The 70%methanol extracts were analyzed using Waters SunFire C18 chromatography column(4.6 mm×250 mm,5 μm),in mobile phase containing acetonitrile-0.2%phosphoric acid solution for gradient elution with volume flow rate of 1.0 mL/min;column temperature was set at 25℃;detection wavelength was set at 230 nm.Results The 9 components had good linear relationship in their respective ranges(r≥0.999 7).The average recoveries were between 98.06%-100.56%and RSD was between 0.48%-2.56%,respectively.Conclusion The method has the advantage of repeatability,simple and fast,and can be used as the quality control of Shujin Tongluo Black Plaster.