OBJECTIVE To investigate the effects and potential mechanism of Yiqi wenyang huwei decoction （YQWY） in improving airway inflammation and remodeling in rats with bronchial asthma （BA） based on the Toll-like receptor 4 （TLR4）/myeloid differentiation primary response protein 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Male SD rats were randomly divided into the normal group， the model group， the dexamethasone group （positive control， 0.5 mg/kg）， and YQWY low-， medium- and high-dose groups （5， 10， 20 g/kg， calculated by the crude drug）， with 8 rats in each group. Except for the normal group， rats in all other groups were sensitized twice with ovalbumin combined with aerosol challenge to establish a BA model. From day 14 to day 34 of the experiment， the rats in each group were administered the corresponding drug solution or normal saline intragastrically， once a day， 1 hour before aerosol challenge. At 24 hours after the final aerosol challenge， asthma symptom scores were assessed， serum levels of immunoglobulin E （IgE） were measured， and the levels of inflammatory cytokines （interleukin-4， interleukin-5， interleukin-13 and tumor necrosis factor-α） and the numbers of inflammatory cells （white blood cell， eosinophil， neutrophil， lymphocyte， monocyte and basophil） in bronchoalveolar lavage fluid were determined. Pathological changes in lung tissue were observed. The mRNA expressions of TLR4， MyD88 and NF-κB， as well as the protein expressions of TLR4， MyD88， NF-κB p65 and phosphorylated NF-κB p65 in lung tissue， were detected. RESULTS Compared with the model group， the pathological changes， such as inflammatory cell infiltration， abnormal deposition of collagen fibers， and goblet cell hyperplasia in the lung tissue of rats in each drug group， were alleviated to varying degrees. The asthma symptom scores （except for the YQWY low-dose group）， the levels of IgE and inflammatory cytokines （except for interleukin-5 in the YQWY medium-dose group）， the number of inflammatory cells （except for monocyte and basophil in the YQWY low-dose group）， the mRNA expression of TLR4， MyD88 and NF-κB， as well as the protein expressions of TLR4， MyD88， NF-κB p65 and phosphorylated NF-κB p65 （except for MyD88 and NF-κB p65 proteins in the YQWY low-dose group as detected by Western blo t） were all significantly reduced or down-regulated （ P ＜0.05 or P ＜0.01）. CONCLUSIONS YQWY can alleviate asthma-like manifestations in BA rats and improve their airway inflammation and remodeling； these effects may be related to the formula’s inhibition of the abnormal activation of the TLR4/MyD88/NF-κB signaling pathway.

Objective To investigate the capacity of municipal and county-level Centers for Disease Control (CDC) in Shandong Province for γ radionuclides in food as well as gross α and gross β in drinking water, and to provide evidence for strengthening radiological laboratories. Method Data regarding radioactive detection capacity were collected from 16 prefecture-level cities and 136 county-level CDCs. Chi-square test and Fisher's exact tests were used to compare capacity differences across regions and between cities with and without nuclear power plants. Correlation analysis was used to evaluate the spatial equity of gross α and gross β detection capacity for drinking water. Result The detection capacity of gross α and gross β in drinking water varied significantly among counties (χ²=81.026, P<0.001），no significant difference was found between coastal and inland cities (χ²=2.021，P>0.155); Cities with nuclear power plants showed better detection capacity (χ²=20.253，P<0.01). The detection capacity for γ radionuclides in food was primarily concentrated in the prefecture-level cities that host nuclear power plants. Conclusion The overall detection capacity for radioactivity in drinking water was acceptable but spatially uneven. The capacity for monitoring radioactive contamination in food was generally weak. It is necessary to strengthen capacity building at the grassroots level.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective:This multicenter retrospective study aimed to analyze the clinicopathological features of duodenal adenocarcinoma (DA) and identify prognostic factors for postoperative survival.Methods:Demographic characteristics, clinicopathological features, treatment outcomes and survival of DA patients undergoing surgical treatment at 18 Chinese medical centers from January 2012 to December 2023 were retrospectively analyzed.Results:Among the 2 056 DA patients included, 46.8% (963) had extra-ampullary DA (EA-DA), and 53.2% (1 093) had peri-ampullary DA (PA-DA). The 1-, 3-, and 5-year overall survival (OS) rates for patients who underwent radical surgery were 93.2%, 71.0%, and 57.2%, respectively. The median overall survival was 76 months, and the median progression-free survival (PFS) was 65 months. No differences in survival were observed between the laparotomy group and minimally invasive surgery (MIS) group either before or after propensity score matching (OS: 76 vs. 75 months before PSM, P=0.986; OS: 75 vs. 75 months after PSM, P=0.602). Furthermore, there were no significant differences between-group in operation time and postoperative complications ( P＞0.05). The MIS group experienced less intraoperative blood loss and shorter hospital stays. The multivariate Cox regression analysis revealed that advanced age ( HR=1.43,95% CI:1.18-1.73), elevated carbohydrate antigen 19-9 levels ( HR=1.24,95% CI:1.02-1.51), perineural invasion ( HR=1.44,95% CI:1.14-1.81), vascular invasion ( HR=1.35,95% CI:1.07-1.71), advanced T stage (T3-4 vs. T1-2: HR=1.86,95% CI:1.49-2.31), regional lymph node metastasis ( HR=1.93,95% CI:1.58-2.36), preoperative biliary drainage ( HR=1.26,95% CI:1.04-1.53), intraoperative blood loss ( HR=1.34,95% CI:1.11-1.62), clinically significant postoperative pancreatic fistulas ( HR=1.53,95% CI:1.12-2.09), and postoperative hemorrhage ( HR=1.62,95% CI:1.14-2.29) were independent risk factors for poor prognosis after surgery (all P＜0.05). Conclusions:Radical surgery is associated with favorable overall survival among DA patients, and no difference in survival is observed between EA-DA and PA-DA patients. MIS is a reliable alternative for DA treatment.

Objective:To investigate the dose characteristics of the Zeiss INTRABEAM system in air and water, providing dose reference for electronic brachytherapy.Methods:A Monte Carlo program was used to establish a three-dimensional model of a miniature X-ray source vacuum drift tube and a 4 cm spherical applicator. The process of electron beam bombardment on a gold target to generate X-rays was simulated, and parameters such as photon fluence spectrum, percentage depth dose, and half-value layer were calculated. Additionally, the radial dose uniformity in water was measured.Results:The average energy of X-rays at 3 cm in air was 20.8 keV, with a half-value layer of 0.08 mm Al. Under the influence of the applicator, the spectrum becomes hardened, with axial and radial average energies of 28.7 and 29.0 keV, respectively. In water, the percentage depth dose (PDD) curve follows an inverse cubic decay with depth, indicating strong dose concentration and rapid fall-off in near-field irradiation. The radial dose uniformity in water exceeded 99.5%.Conclusions:The INTRABEAM device emits low-energy X-rays characterized by shallow penetration depth, and concentrated dose delivery. Its highly uniform dose distribution ensures comprehensive coverage of the target area, making it particularly suitable for treating superficial tumors and for intraoperative radiotherapy at close range.

BACKGROUND:Plasma coagulation factors have been shown to be strongly associated with chronic kidney disease in many observational studies.Nevertheless,the causal relationship between plasma coagulation factors and chronic kidney disease has not been fully revealed.OBJECTIVE:To assess and explore the association between plasma coagulation factors and chronic kidney disease risk using a two-sample Mendelian randomization approach.METHODS:Genome-wide association study data of 39 plasma coagulation factors with different ID numbers were obtained from the GWAS Catalog database and chronic kidney disease genome-wide association analysis data(ebi-a-GCST003374)were obtained from the Open Genome-Wide Association Study database(IEU Open GWAS),where the sample size of the chronic kidney disease dataset was 117 165 cases and the number of single nucleotide polymorphisms was 2 179 497.Inverse variance weighting,MR-Egger regression,weighted median,weighted mode,and simple mode were used to explore causality.Meanwhile,Cochran Q test was used to assess the variability of single nucleotide polymorphism loci.Horizontal pleiotropy of single nucleotide polymorphisms was verified by MR-Egger intercept test.Sensitivity analyses were performed using the"leave-one-out"method to determine whether the Mendelian randomization results would be confounded by a single single nucleotide polymorphism site.RESULTS AND CONCLUSION:(1)A total of four plasma coagulation factors were associated with chronic kidney disease by Mendelian randomization analysis of 39 plasma coagulation factors and chronic kidney disease.Plasma coagulation factor V(FV)level(odds ratio[OR]=0.922,95％confidence interval[CI]:0.875-0.971,P=0.002),plasma FVII level(OR=0.719,95％CI:0.521-0.991,P=0.044),plasma FXa level(OR=1.113,95％CI:1.009-1.227,P=0.032),plasma antithrombin-level(OR=0.849,95％CI:0.739-0.975,P=0.020)were significantly associated with chronic kidney disease(all P＜0.05).Horizontal pleiotropy and heterogeneity were not detected.(2)Based on the two-sample Mendelian randomization in the genetic epidemiologic method,plasma FVII level,plasma antithrombin-level,and plasma FV level of coagulation factors were protective factors for the risk of chronic kidney disease,and plasma FXa level was a risk factor of chronic kidney disease.(3)The above results confirm that there is a significant potential causal relationship between plasma coagulation factors and chronic kidney disease.Although we analyzed the data of European populations from international databases,these data analyses have a reference value for the study of chronic kidney disease and coagulation factors in China,and they also provide innovative insights into the study of the genetic epidemiology of chronic kidney disease,and they also provide a certain reference value for the in-depth study of the related databases in China,including the China Health and Retirement Longitudinal Study database.Future studies can focus on the assessment of hypocoagulability or hypercoagulability of related coagulation factors in patients with chronic kidney disease.

OBJECTIVE: To compare the diagnostic accuracy of supraspinatus muscle outlet X-ray film, oblique sagittal multislice helical CT (MSCT), and oblique sagittal MRI in the diagnosis of subacromial impingement syndrome (SIS). METHODS: A retrospective analysis was conducted on the imaging data of 106 patients diagnosed with SIS between January 2023 and December 2024. The cohort consisted of 32 males and 74 females, with ages ranging from 43 to 70 years (mean, 60.19 years). All patients underwent supraspinatus muscle outlet X-ray film, MSCT, and MRI scans, with MSCT further subjected to three-dimensional reconstruction. Two experienced radiologists independently evaluated the acromion morphology in each imaging modality using the Bigliani classification system. Inter-observer reliability was assessed via Kappa statistics. The CT three-dimensional reconstructions were used as the "gold standard". The overall consistency, Kappa values, sensitivity, and specificity of the three imaging modalities were calculated. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was computed. RESULTS: The inter-observer reliability for supraspinatus muscle outlet X-ray film, oblique sagittal MSCT, and oblique sagittal MRI was moderate, with Kappa values of 0.62, 0.63, and 0.55, respectively. When compared to the CT three-dimensional reconstructions as the "gold standard", the overall consistency was 88.7% (94/106), 62.3% (66/106), and 58.5% (62/106), respectively. The supraspinatus muscle outlet X-ray film showed excellent consistency (Kappa=0.77), whereas the consistency of MSCT and MRI was lower (Kappa=0.34 and 0.29, respectively). In terms of diagnostic sensitivity and specificity, the supraspinatus muscle outlet X-ray film outperformed oblique sagittal MSCT and oblique sagittal MRI in distinguishing various acromion types. ROC analysis demonstrated that the AUC for the supraspinatus muscle outlet X-ray film was consistently higher than for oblique sagittal MSCT and oblique sagittal MRI, with the highest diagnostic performance observed for type Ⅲ hooked acromion (AUC=0.939). CONCLUSION Supraspinatus muscle outlet X-ray film provides the highest diagnostic accuracy for acromion classification in SIS patients, particularly in identifying type Ⅲ hooked acromion, which is strongly associated with SIS. Given its superior sensitivity and consistency, it should be considered the primary screening tool. MSCT and MRI serve as valuable supplementary modalities for complex cases and preoperative evaluation.
Humans ; Middle Aged ; Male ; Female ; Shoulder Impingement Syndrome/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Retrospective Studies ; Aged ; Adult ; Imaging, Three-Dimensional ; Sensitivity and Specificity ; Tomography, Spiral Computed/methods* ; Multidetector Computed Tomography/methods* ; Reproducibility of Results

BACKGROUND:The pathogenesis of osteoporosis is closely related to the immune system.A comprehensive and in-depth study of the relationship between immunity and osteoporosis is crucial for understanding and treating the disease.OBJECTIVE:To investigate the role of immune cells in osteoporosis using single-cell sequencing technology.METHODS:Femoral head tissue samples from osteoporosis and non-osteoporosis patients were downloaded from GEO database and analyzed using single-cell sequencing.Data analysis,including cell clustering,functional enrichment,pseudotime trajectory,and cell interaction analyses,was performed using R4.3.0 and software packages such as Seurat v.4.3,monocle(2.28.0),and CellChat.The femoral head tissues of patients with femoral neck fracture who underwent artificial hip replacement surgery were obtained,including two cases of osteoporosis patients and two cases of non-osteoporosis patients.Immunohistochemical staining was used to detect the protein expression of CCL13 and CCL18.qPCR was used to detect the immunoglobulin heavy constant γ-4,immunoglobulin λ constant 3,human class Ⅱ major histocompatibility complex DRβ1,and CD83 mRNA expression.Western blot was used to detect the protein expression of receptor-type tyrosine protein phosphatase C,CD22,and CD99.RESULTS AND CONCLUSION:Transcriptomic analysis identified 10 cell clusters,including osteoclasts,myeloid cells,T cells,osteoblasts,macrophages,monocytes,erythrocytes,B cells,bone marrow mesenchymal stem cells,and mast cells.There was an increase in the ratio of osteoclasts to T cells and a decrease in the ratio of osteoblasts to B cells in the femoral head tissue of the osteoporosis group.Among the B-cell subpopulations,the proportion of B-cells of taxa 1,3(BC1,BC3)in the femoral head tissue of the osteoporosis group was higher than that of the non-osteoporosis group,and the proportion of B-cells of taxa 2(BC2)was less than that of the non-osteoporosis group.BC1 was enriched significantly for labels such as regulation of adaptive immune response,somatic recombination of immune receptors,and modulation of lymphocyte-mediated immunity,while BC3 was enriched significantly for labels such as regulation of immunoglobulin production,response to type Ⅱ interferon,apoptotic processes involving cysteine endopeptidases,and cytotoxicity.The communication intensity between B-cell subtype BC1 and osteoblasts in the femoral head tissue of the osteoporosis group was higher than that of the non-osteoporosis group,while the communication intensity between BC3 and BC1 was also increased.The communication between BC3 and BC1 was significantly enriched in the CD22-receptor-type tyrosine protein phosphatase C pathway;the communication between BC1 and osteoblasts was mainly enriched in the CD99-CD99 pathway;and the communication between BC3 and osteoblasts was also highly enriched in the CD99-CD99 pathway.Protein expression of CCL13,CCL18,receptor-type tyrosine protein phosphatase C,CD22,CD99,immunoglobulin heavy constant γ-4,immunoglobulin λ constant 3,human class Ⅱ major histocompatibility complex DRβ1,and CD83 mRNA were higher in femoral tissues of the osteoporosis group than those of the non-osteoporosis group(P＜0.05).To conclude,specific B cell subpopulations can influence the differentiation and apoptosis of osteoblasts in the femoral tissue of osteoporosis patients.

Objective:To explore and demonstrate the effect of general-specialty hierarchical management mode for chronic heart failure (CHF) in community.Methods:This was a single-blind, randomized, controlled study. A total of 530 CHF inpatients who attended Weifang Community Health Service Center (WCHSC) in Pudong New Area from February 2018 to September 2019 were consecutively enrolled. A random number table method was used to divide the patients into the management group ( n=265) and control group ( n=265). The demographic data and past medical history were collected 1 day before enrolment (baseline), and patients were assessed for New York Heart Association (NYHA) cardiac function classification and tested for blood N-terminal B-type natriuretic peptide proteins (NT-proBNP) levels, while Doppler echocardiography was performed to obtain the relevant indexes. The management group used a comprehensive management mode, co-delivered by both WCHSC (offering primary care) and RHSJUSM (offering specialty care) at Renji-Weifang CHF Studio in WCHSC , using the jointly developed CHF hierarchical CHF diagnosis and treatment criteria and referral procedure under the condition of sharing drugs and laboratory test results for CHF. The control group received routine heart failure care. Intergroup comparisons were made on baseline data obtained before follow-up and on NT-proBNP , left ventricular ejection fraction (LVEF), NYHA functional class , re-hospitalization rate and mortality rate at the end of the 6-month follow-up. Results:A total of 506 cases completed the follow-up. There were 253 patients in the management group, aged (68.26±9.41) years, 117 males (46.2%); 253 were in the control group, aged (66.98±9.63) years, 115 males (45.5%). There were no statistically significant differences in age, sex, marital status, education level, and comorbidities between the two groups (all P>0.05). At baseline, the differences in LVEF and NT-proBNP between the two groups were not statistically significant (all P>0.05), and at 6 months of intervention, LVEF, and NT-proBNP had significantly improved in both groups (all P<0.05) . Moreover, LVEF was higher in the management group than in the control group, and NT-proBNP was lower than in the control group (both P<0.01). At baseline, there were 166 cases (65.6%) in the control group with NYHA class Ⅲ/Ⅳ, and 145 cases (57.3%) in the comprehensive management group. There was no statistically significant difference between the two groups ( P>0.05). At 6 months of intervention, the percentage of NYHA class Ⅲ/Ⅳ patients in the comprehensive management group was lower than at baseline ( P<0.01),while that in the control group was higher than at baseline ( P<0.01), and the comprehensive management group was lower than that in the control group ( P<0.01). During the follow-up period, the rehospitalization rate for CHF in the management group was 13.83%(35/253), which was lower than that in the control group, which was 26.88%(68/253) ( P<0.001). Conclusion:The comprehensive management mode of CHF in the community through collaboration between general and specialized departments can significantly improve the management effect, suggesting that this mode is effective and can be promoted.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.