Objective:To investigate expression of IL-36 in ulcerative colitis(UC),and to assess regulatory activity of IL-36 receptor antagonist(IL-36Ra)to monocytes function in UC patients.Methods:Seventy-two UC patients and twenty controls were enrolled between April 2021 and January 2023 in the First Affiliated Hospital of Xinxiang Medical University.Plasma and peripheral blood mononuclear cells(PBMCs)were isolated.Tissue infiltrating lymphocytes(TILs)were isolated from UC tissue and normal tis-sue.Monocytes from PBMCs and TILs were purified.Plasma IL-36α,IL-36β,IL-36γ and IL-36Ra levels were measured by ELISA.mRNA levels of IL-36 in tissue and IL-36 receptor subunits in monocytes were semi-quantified by real-time PCR.Purified monocytes were stimulated with recombinant IL-36Ra and co-culture with CaCO2 cells.Percentage of CaCO2 cell death was measured.Serum TNF-α,granzyme B and granzyme H levels were measured by ELISA.Mean fluorescence intensity(MFI)of Fas ligand(FasL)and TNF-related apoptosis-inducing ligand(TRAIL)in monocytes was measured by flow cytometry.Results:There were no significant differences of plasma IL-36α,IL-36β or IL-36γ levels between UC group and control group(P>0.05).Plasma IL-36Ra levels were lower in UC group compared with control group[(87.33±11.95)pg/ml vs(100.81±15.62)pg/ml,t=4.162,P<0.001].There were no significant differences of IL-36α,IL-36β or IL-36γ mRNA levels between UC tissue and normal tissue(P>0.05).IL-36Ra mRNA level was remarkably reduced in UC tissue compared with normal tissue(1.00±0.23 vs 1.36±0.21,t=5.500,P<0.001).There were no signifi-cant differences of IL-36 receptor subunits mRNA relative levels between UC group and control group,as well as between UC tissue and normal tissue(P>0.05).Peripheral monocytes-induced CaCO2 cell death was higher in UC group compared with control group[(14.45±3.33)%vs(10.92±2.87)%,t=2.965,P=0.005].Monocyes purified from UC tissue also mediated increased CaCO2 cell death compared with those from normal tissue[(17.41±4.19)%vs(14.31±3.02)%,t=2.327,P=0.027].TNF-α,granzyme B and granzyme H levels in supernatants were significantly elevated(P<0.05).However,there were no remarkable differences of FasL or TRAIL MFI in monocytes between UC group and control group,as well as between UC tissue and normal tissue(P>0.05).Recombi-nant IL-36Ra stimulation reduced CaCO2 cell death was decreased in both monocytes purified from peripheral blood and UC tissue in UC patients(P<0.05),TNF-α,granzyme B and granzyme H levels in supernatants were also down-regulated(P<0.05).There were no remarkable differences of FasL or TRAIL MFI in monocytes between cells with and without IL-36Ra stimulation(P>0.05).Conclu-sion:IL-36Ra may suppress monocytes cytotoxicity through down-regulation of TNF-α and granzyme secretions in UC patients.

Objective:To investigate expression of IL-36 in ulcerative colitis(UC),and to assess regulatory activity of IL-36 receptor antagonist(IL-36Ra)to monocytes function in UC patients.Methods:Seventy-two UC patients and twenty controls were enrolled between April 2021 and January 2023 in the First Affiliated Hospital of Xinxiang Medical University.Plasma and peripheral blood mononuclear cells(PBMCs)were isolated.Tissue infiltrating lymphocytes(TILs)were isolated from UC tissue and normal tis-sue.Monocytes from PBMCs and TILs were purified.Plasma IL-36α,IL-36β,IL-36γ and IL-36Ra levels were measured by ELISA.mRNA levels of IL-36 in tissue and IL-36 receptor subunits in monocytes were semi-quantified by real-time PCR.Purified monocytes were stimulated with recombinant IL-36Ra and co-culture with CaCO2 cells.Percentage of CaCO2 cell death was measured.Serum TNF-α,granzyme B and granzyme H levels were measured by ELISA.Mean fluorescence intensity(MFI)of Fas ligand(FasL)and TNF-related apoptosis-inducing ligand(TRAIL)in monocytes was measured by flow cytometry.Results:There were no significant differences of plasma IL-36α,IL-36β or IL-36γ levels between UC group and control group(P>0.05).Plasma IL-36Ra levels were lower in UC group compared with control group[(87.33±11.95)pg/ml vs(100.81±15.62)pg/ml,t=4.162,P<0.001].There were no significant differences of IL-36α,IL-36β or IL-36γ mRNA levels between UC tissue and normal tissue(P>0.05).IL-36Ra mRNA level was remarkably reduced in UC tissue compared with normal tissue(1.00±0.23 vs 1.36±0.21,t=5.500,P<0.001).There were no signifi-cant differences of IL-36 receptor subunits mRNA relative levels between UC group and control group,as well as between UC tissue and normal tissue(P>0.05).Peripheral monocytes-induced CaCO2 cell death was higher in UC group compared with control group[(14.45±3.33)%vs(10.92±2.87)%,t=2.965,P=0.005].Monocyes purified from UC tissue also mediated increased CaCO2 cell death compared with those from normal tissue[(17.41±4.19)%vs(14.31±3.02)%,t=2.327,P=0.027].TNF-α,granzyme B and granzyme H levels in supernatants were significantly elevated(P<0.05).However,there were no remarkable differences of FasL or TRAIL MFI in monocytes between UC group and control group,as well as between UC tissue and normal tissue(P>0.05).Recombi-nant IL-36Ra stimulation reduced CaCO2 cell death was decreased in both monocytes purified from peripheral blood and UC tissue in UC patients(P<0.05),TNF-α,granzyme B and granzyme H levels in supernatants were also down-regulated(P<0.05).There were no remarkable differences of FasL or TRAIL MFI in monocytes between cells with and without IL-36Ra stimulation(P>0.05).Conclu-sion:IL-36Ra may suppress monocytes cytotoxicity through down-regulation of TNF-α and granzyme secretions in UC patients.

ObjectiveTo investigate the effect of Tongxinluo capsules on the use of anti-ischemic drugs in patients with chronic coronary syndrome （CCS） of Qi deficiency and blood stasis. MethodA multicenter，prospective cohort study was conducted，with Tongxinluo capsules intervention as the exposure factor. Patients were divided into an exposed group （combination of traditional Chinese and western medicine） and a non-exposed group （western medicine alone），and followed up for one year. The use of anti-ischemic drugs was observed on the day of enrollment and at 3，6，12 months. ResultA total of 186 patients were enrolled，with 128 in the exposed group and 58 in the non-exposed group. There were no statistically significant differences in baseline characteristics between the two groups. At the 3-month follow-up，the types of first-line anti-ischemic drugs used in the exposed group were significantly fewer than those in the non-exposed group （P<0.01），and this difference remained statistically significant at 6 months （P<0.05） but was no longer significant at 12 months. At the 3- and 6-month follow-ups，there were no significant differences between the two groups in the types of second-line anti-ischemic drugs used. However，at the 12-month follow-up，the types of second-line anti-ischemic drugs used in the exposed group were significantly fewer than those in the non-exposed group （P<0.01）. At the 3-month follow-up，both groups showed a reduction in the types of first-line anti-ischemic drugs used compared to baseline （P<0.05），with a more pronounced reduction in the exposed group （P<0.05）. At the 6-month follow-up，the exposed group showed a significant reduction in the types of second-line anti-ischemic drugs used compared to baseline （P<0.05），while no significant changes were observed in the non-exposed group. At the 12-month follow-up，the difference in the types of second-line anti-ischemic drugs between the exposed and non-exposed groups was statistically significant （P<0.05），while there was no significant difference in the types of first-line anti-ischemic drugs. ConclusionTongxinluo capsules can effectively reduce the use of anti-ischemic drugs in patients with CCS of Qi deficiency and blood stasis.

Objective To investigate the effect of thalidomide combined with infliximab (IFX) in treatment of refractory inflammatory bowel disease (IBD) and its effects on insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1). Methods A total of 120 patients with refractory IBD were randomly divided into experimental group and control group, with 60 cases in each group. The two groups were given conventional treatment (mesalazine), the control group was given IFX, and the experimental group was given IFX combined with thalidomide, continuous treatment for two months. The efficacy, intestinal flora disturbance rate, adverse reactions, Crohn's disease activity index (CDAI), Lewis score, serum IGF-1, TGF-β1 levels and nutritional status indexes[albumin (ALB), transferrin (Tf)]before and after treatment for 1 month and 2 months of the two groups were compared. Results The total effective rate of the experimental group was significantly higher than that of the control group (P < 0.05). After one month and two months of treatment, CDAI and Lewis scores of the experimental group were significantly lower than those of the control group (P < 0.05); the serum levels of IGF-1, TGF-β1 as well as ALB and Tf in the experimental group were significantly higher than those in the control group (P < 0.05). The improvement of intestinal flora disturbance rate in the experimental group was significantly better than that in the control group (P < 0.05). There was no significant difference in the incidence of oral and nasal mucosa dryness, throat discomfort, nausea and vomiting between two groups (P>0.05). Conclusion In the treatment of refractory IBD patients, thalidomide combined with IFX can regulate serum IGF-1 and TGF-β1 levels, effectively relieve clinical manifestations, inhibit inflammatory activities, and improve nutritional status and intestinal flora disorders of patients, and it has high safety.

Objective:To improve the users’ comfort of steady-state visual evoked potential (SSVEP)-based brain-computer interface (BCI) through high-frequency stimulation and overcome the problem of accuracy decline caused by high frequency by combining dual-frequency encoding.Methods:Two dual-frequency high-frequency 60-instruction paradigms based on left and right visual fields and checkerboard stimuli were designed based on the 25.5 - 39.6 Hz frequency. Thirteen subjects participated in the experiment, and spectrum and spatial characteristics analyses were performed on SSVEP signals. The filter bank parameters were optimized based on the spectrum characteristics. Extended canonical correlation analysis (eCCA), ensemble task-related component analysis (eTRCA), and task-discriminant component analysis (TDCA) were used for SSVEP recognition.Results:Stable SSVEP was successfully induced in both the left and right visual fields and the checkerboard grid paradigm. The left and right visual fields had high signal-to-noise ratios for the fundamental frequency and its harmonics and weak signal-to-noise ratios for intermodulation components, whereas the intermodulation components of the 2 stimulus frequencies of the checkerboard grid, f1 + f2, had significantly higher signal-to-noise ratios than the second harmonic components above 30 Hz, and there was also a f2 ? f1 component and a 2 f1 ? f2 component. Combined with brain topography, it can be seen that the f1 and f2 response components of the left and right visual fields are located on opposite sides of the visual field, while the checkerboard grids are both concentrated in the center of the occipital region. Regarding the lateralization of brain topography amplitude and signal-to-noise ratio, the mean values of the PO3 and PO4 signal-to-noise ratios at the stimulation frequency of the left and right visual fields are consistent with the contralateral response characteristics. The 5 fb ? 1 method is the optimal filter set setting method, and the recognition correctness rate of TDCA for the left and right visual fields is the highest. However, the comparison of the recognition correctness rate of tessellated lattice eTRCA and TDCA is not statistically significant ( P > 0.05). The information transmission rates of the three algorithms all increase and then decrease with the increase in data length. Conclusions:The designed dual-frequency, high-frequency SSVEP-BCI paradigm is able to better balance performance and comfort and provides a basis for practical large instruction set BCI design methods.

Objective:To construct and validate a theoretical model of residents′ willingness to participate in tiered medical care based on harmonious management theory, providing reference for promoting the tiered medical care system and aiding governmental decision-making.Methods:Based on the harmonious management theory and literature review, a model capturing residents′ propensity to engage in tiered medical care was formulated. Using convenience sampling method, a questionnaire survey was conducted on 2 067 residents from 24 communities in Zhejiang province from April to May 2022. Descriptive statistical analysis was conducted on the survey results, and multilevel linear regression and structural equation modeling were used to analyze the driving mechanism of residents′ willingness to participate in tiered medical care.Results:The willingness rate of residents to participate in tiered medical care was 69.7%, which was at an average level. Regression insights highlighted the positive influence of policy support perception ( β=0.170, P<0.01), awareness of management mechanisms ( β=0.093, P<0.01), cognitive attitudes ( β=0.102, P<0.01), and trust levels ( β=0.244, P<0.01) on residents′ participation willingness. In contrast, resource allocation perceptions lacked a significant effect ( β=0.065, P>0.05). The structural equation model revealed that cognitive attitudes played a mediating role in the " policy system perception → participation willingness" and " management mechanism perception → participation willingness" pathways, with effect sizes of 0.030 and 0.039, respectively. Trust levels also mediated these paths, with effect sizes of 0.039 and 0.045, and entirely mediated the " resource allocation perception → participation willingness" path, registering an effect size of 0.053. Conclusions:The harmonious management theory can be used to explain the formation mechanism of residents′ willingness to participate in tiered medical care. The government and medical institutions urgently need to further improve residents′ awareness of tiered medical care, focus on enhancing residents′ trust, and further improve policies and management measures such as financial investment, medical insurance reimbursement, and referral systems.

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

Objective:To document the blood indexes of middle-aged and elderly intracerebral hemorrhage (ICH) patients complicated with deep vein thrombosis (DVT).Methods:A retrospective analysis was conducted of 77 hospitalized ICH patients using venous color Doppler ultrasonography within 3 days of admission. According to the results, they were divided into a DVT group (18 cases) and a non-DVT group (59 cases). The blood routine, biochemistry, coagulation, and D-dimer examinations were conducted on the 2nd day after admission. T-tests and rank sum tests tested the significance of any differences between the groups in average white blood cell counts, neutrophil percentages, platelets, albumin, globulin, fasting blood glucose, urea nitrogen, creatinine, uric acid, electrolytes, fibrinogen or D-dimer.Results:The average levels of albumin, uric acid and calcium in the DVT group were significantly lower than in the non-DVT group. The average levels of fasting blood glucose and D-dimer were significantly higher.Conclusions:Decreased serum uric acid, calcium and albumin levels, together with increased fasting blood glucose and D-dimer are related to the occurrence of DVT in ICH patients. To reduce the risk of DVT it is important to maintain normal levels of serum uric acid, calcium and albumin and to limit D-dimer and fasting blood glucose.

Objective:To evaluate whether the decrease in peripheral blood monocyte count was a potential predictor for neutropenia in patients with nasopharyngeal carcinoma and cervical cancer.Methods:The medical records of 95 patients with nasopharyngeal carcinoma and cervical carcinoma who received intensity-modulated radiation therapy (IMRT) combined with paclitaxel liposomes and platinum (TP) synchronous chemotherapy and presented with neutropenia in the Second Affiliated Hospital of Soochow University from January 2017 to December 2018 were retrospectively analyzed. Paired sample t-test was used to assess whether the number of days when the monocytes initially dropped/decreased to lowest level/eventually increased to normal value was significantly less than those of the neutrophils. In addition, the chi-square test was performed to determine the correlation between the degree of reduction in the absolute neutrophil count (ANC) and baseline absolute monocyte count (AMC). Results:The change trend of AMC was consistent with that of ANC in the two cycles of concurrent chemotherapy. The number of days when AMC initially decreased/decreased to the lowest level/finally increased to normal value was significantly less than that of ANC (4 d vs. 6 d, 4 d vs. 10 d, P<0.001; 5 d vs. 6 d, 6 d vs. 9 d, 7 d vs. 12 d, P<0.001). However, no correlation was found between the baseline level of monocytes and the degree of subsequent neutropenia [(AMC<0.4×10 9) vs.( AMC≥0.4×10 9)=32 vs. 63, P=0.172]. Conclusions:Decreased monocyte count is an important potential predictor for neutropenia and a significant indicator for guiding the next monitoring of neutrophil count and treatment with granulocyte colony-stimulating factor.

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Chemistry, Clinical/standards* ; China ; Indicators and Reagents ; Reagent Kits, Diagnostic/standards*