ObjectiveTo explore the correlation between the occurrence of cardiovascular events in rheumatoid arthritis（RA） and traditional Chinese medicine（TCM） syndrome. MethodsThe cross-sectional study selected 6713 RA patients from 122 centres nationwide， in which general information such as name， gender， age， height， body weight， and course of disease were collected by completing a questionnaire； patients were classified into eight types of syndrome according to the information of their four examinations，i.e. wind-dampness obstruction syndrome， cold-dampness obstruction syndrome， dampness-heat obstruction syndrome， phlegm-stasis obstruction syndrome， stasis-blood obstructing collateral syndrome， qi-blood deficiency syndrome， liver-kidney insufficiency syndrome， and qi-yin deficiency syndrome. According to the occurrence of cardiovascular events， they were divided into the occurrence group and the non-occurrence group， and the condition assessment data and laboratory examination indexes were recorded. The test of difference between groups was used to analyse the possible risk factors for the occurrence of RA cardiovascular events， and binary logistic regression was used to analyse the correlation between TCM syndromes and RA cardiovascular events. ResultsA total of 6713 RA patients were included， including 256 cases in occurrence group and 6457 in non-occurrence group. There was no statistically significant difference between groups in terms of height， gender， insomnia， appetite， white blood cell（WBC）， hemoglobin（HGB）， platelets（PLT）， rheumatoid factor（RF）， anti-cyclic peptide containing citrulline（CCP）， alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， γ-glutamyl transpeptidase（GGT）， urea creatinine（CREA）， and glucose（GLU）（P＞0.05）. The TCM syndromes between groups showed significant statistic differences（P＜0.05）. Patients in occurrence group had longer disease duration， heavier body weight， and older age； more severe conditions such as disease activity（DAS-28）， number of painful joints（TJC）， number of swollen joints（SJC）， health questionnaire scores（HAQ）， visual analog scores（VAS）， restlessness， and fatigue； higher blood sedimentation rate（ESR）， low-density lipoprotein（LDL-C）， triglyceride（TG）， total cholesterol（TC）， D-Dimer， and lower high-density lipoprotein（HDL-C）（P＜0.05）. The distribution of syndrome types showed that dampness-heat obstruction syndrome accounted for the largest proportion of patients in both groups and was higher in RA cardiovascular events. Logistic regression analysis showed that the occurrence of RA cardiovascular events was strongly associated with dampness-heat obstruction syndrome［OR=5.937， 95%CI （4.434， 7.949）， P＜0.001］. ConclusionThe occurrence of RA cardiovascular events were associated with TCM syndromes， and the probability of cardiovascular events in the RA patients with dampness-heat obstruction syndrome was 5.937 times higher than patients with other TCM syndromes.

OBJECTIVE: To investigate the efficacy and safety of the conditioning regimen BeEAM (bendamustine+et-oposide+cytarabine+melphalan) in autologous stem cell transplantation (ASCT) for patients with malignant lymphoma. METHODS: The clinical data of 20 patients with malignant lymphoma who underwent ASCT after conditioning with BeEAM regimen from January 2021 to December 2022 in the First Affiliated Hospital of Bengbu Medical University were collected, and the clinical characteristics before transplantation, conditioning-related toxicity, hematopoietic reconstitution after transplantation, and therapeutic effects were analyzed. 67 patients with malignant lymphoma who did not undergo ASCT during the same period were selected as the control group, and the 1-year progression-free survival (PFS) rate and overall-survival (OS) rate between the ASCT group and the non-ASCT group were compared. RESULTS: 15 cases achieved complete remission (CR) and 5 cases achieved partial remission (PR) before transplantation in ASCT group. During the conditioning process of patients in the ASCT group, 14 cases experienced gastrointestinal adverse reactions, 13 cases experienced neutropenic fever, 10 cases experienced oral mucositis, 2 cases experienced abnormal liver function, and only 1 case experienced acute renal injury. All the adverse reactions resolved after symptomatic treatment. After transplantation, 19 cases achieved hematopoietic reconstitution, and only one case had poor platelet engraftment. The median time of peripheral white blood cell (WBC) engraftment was 9 (9-16) days, and the median time of platelet engraftment was 12 (10-23) days. By the end of follow-up, there were no transplant-related deaths. The 1-year PFS rates in the ASCT group and the non-ASCT group were 94.4% and 68.5%, respectively; The 1-year OS rates were 94.4% and 83.5%, respectively. The median PFS and OS time for both groups were not reached. The PFS in the ASCT group was significantly better than that in the non-ASCT group (P < 0.05), and there was no significant difference in OS between the two groups ( P >0.05). CONCLUSION BeEAM regimen is safe and effective as a conditioning treatment for ASCT in patients with malignant lymphoma, with tolerable adverse reactions, controllable non-hematological toxicity, smooth hematopoietic reconstitution, and considerable short-term efficacy. However, further follow-up is required to evaluate its long-term efficacy.
Humans ; Transplantation Conditioning/methods* ; Transplantation, Autologous ; Hematopoietic Stem Cell Transplantation ; Lymphoma/therapy* ; Cytarabine/therapeutic use* ; Female ; Male ; Melphalan/therapeutic use* ; Adult ; Middle Aged ; Bendamustine Hydrochloride/therapeutic use*

BACKGROUND: It is inaccurate to reflect the level of dust exposure through working years. Furthermore, identifying a predictive indicator for lung function decline is significant for coal miners. The study aimed to explored whether club cell secretory protein (CC16) levels can reflect early lung function changes. METHODS: The cumulative respiratory dust exposure (CDE) levels of 1,461 coal miners were retrospectively assessed by constructed a job-exposure matrix to replace working years. Important factors affecting lung function and CC16 were selected by establishing random forest models. Subsequently, the potential of CC16 to reflect lung injury was explored from multiple perspectives. First, restricted cubic spline (RCS) models were used to compare the trends of changes in lung function indicators and plasma CC16 levels after dust exposure. Then mediating analysis was performed to investigate the role of CC16 in the association between dust exposure and lung function decline. Finally, the association between baseline CC16 levels and follow-up lung function was explored. RESULTS: The median CDE were 35.13 mg/m³-years. RCS models revealed a rapid decline in forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), and their percentages of predicted values when CDE exceeded 25 mg/m³-years. The dust exposure level (<5 mg/m³-years) causing significant changes in CC16 was much lower than the level (25 mg/m³-years) that caused changes in lung function indicators. CC16 mediated 11.1% to 26.0% of dust-related lung function decline. Additionally, workers with low baseline CC16 levels experienced greater reductions in lung function in the future. CONCLUSIONS CC16 levels are more sensitive than lung indicators in reflecting early lung function injury and plays mediating role in lung function decline induced by dust exposure. Low baseline CC16 levels predict poor future lung function.
Uteroglobin/blood* ; Humans ; Dust/analysis* ; Occupational Exposure/analysis* ; Male ; Middle Aged ; Adult ; Retrospective Studies ; Lung Injury/chemically induced* ; Coal Mining ; Biomarkers/blood* ; China/epidemiology* ; Air Pollutants, Occupational ; Female

Gastrointestinal dyskinesia is a central factor contributing to the development of functional dyspepsia(FD),which is characterized by the rupture of the gastrointestinal nerve-Cajal interstitial cell-smooth muscle network.Gan Yu Pi Xu are similar to endoplasmic reticulum stress(ERs)-mitochondrial autophagy homeostasis imbalance.Mitochondrial autophagy disorders are the biological basis of Pi Xu,and Gan Yu is the macroscopic manifestation of ERs,and regulation of ERs-mitochondrial autophagy pathway is an important way to prevent and control FD.In this paper,we start from the theory of"liver-spleen correlation",combine the changes of endoplasmic reticulum and mitochondria in the process of gastrointestinal dyskinesia,reveal the correlation between the pathogenesis of Gan Yu Pi Xu and the autophagy of ERs and mitochondria,and elucidate the mechanism of gastrointestinal dyskinesia by the method of Shu Gan Jian Pi,so as to provide a new point of view for the treatment of gastrointestinal dyskinesia in FD.

OBJECTIVE To explore the characteristics of adverse drug reaction （ADR） induced by semaglutide and provide a reference for clinically safe medication. METHODS Using search terms such as “semaglutide” and “adverse reactions” in both Chinese and English， the case reports about ADRs caused by semaglutide were searched and analyzed from PubMed， Web of Science， SpringerLink， CNKI， Chinese Medical Journal Full-text Database， Wanfang Medical Network and VMIS. RESULTS Overall 14 literature were included， involving 17 patients. Among 17 patients， 9 were female and 8 were male， with the age ranging from 25 to 80 years. Eight patients were given two or more drugs， and eight patients took 0.25 mg as the initial dose； the ADR occurred most frequently within 6 months （94.12%）. Sixteen patients’ symptoms improved or recovered after drug withdrawal and symptomatic treatment. Eleven patients did not mention whether to continue to use semaglutide in the future. Nine patients underwent ADR correlation evaluation， and 1， 3， 1 and 4 cases were determined to be “definite”，“ probable”，“ possible”， and “doubtful” respectively. Semaglutide-induced ADRs involved multiple organs or systems， most of which were the digestive system （35.29%）， followed by skin tissue （29.41%）. Among them， acute gastric dilation， severe liver injury， calculous cholecystitis， bullous pemphigoid， eosinophilic fasciitis， acute kidney injury， acute interstitial nephritis， depression and acute hemolytic anemia were not mentioned in the instruction. CONCLUSIONS ADRs caused by semaglutide can occur in all ages， mainly within 6 months after medication， and mainly involve the digestive system， skin tissue， etc. Great attention should be paid to pharmaceutical care for those patients with liver and kidney dysfunction， neuropsychiatric diseases， glucose-6-phosphate dehydrogenase deficiency， etc. When ADR occurs， drug withdrawal and symptomatic treatment should be performed promptly to ensure patients’ medication safety.

OBJECTIVE To introduce a case of interstitial pneumonia induced by vedolizumab （VDZ）， summarize and analyze the characteristics of the occurrence of VDZ-associated lung toxicity， and provide a reference for the clinically safe use of drugs. METHODS From the perspective of clinical pharmacists， the diagnosis and treatment of a case of VDZ-induced interstitial pneumonia were retrospectively analyzed， and the association of adverse drug reactions （ADR） was analyzed. Retrieving from Chinese and English databases such as CNKI， VIP， PubMed and Web of Science， case reports of VDZ-associated lung toxicity were summarized and analyzed. RESULTS The patient developed interstitial pneumonia during the use of VDZ and empirical anti- infective therapy with antibiotics was ineffective. After withdrawal of VDZ and treatment with methylprednisolone， symptoms and imaging examinations improved， but interstitial pneumonia still existed. According to Naranjo’s ADR evaluation scale and based on China Adverse Drug Reaction Reporting and Monitoring Manual， the association between VDZ and interstitial pneumonia was “very likely”. Results of the literature analysis showed that among 29 involved patients （including the patient reported in this article）， there were 19 males and 10 females， with an average age of （49.24±17.06） years. Lung toxicity mainly included VDZ- associated pneumonia， eosinophilic pneumonia， pulmonary granulomas or necrobiotic nodules， interstitial lung injury， etc.， which mostly occurred ≤24 weeks after medication （58.62%）. The main clinical manifestations included cough， dyspnea and fever. The vast majority of patients improved or recovered after drug withdrawal and/or glucocorticoid treatment， but one patient died of respiratory failure. CONCLUSIONS Lung toxicity is a rare ADR of VDZ with insidious onset and nonspecific symptoms. Once patients experience symptoms such as cough and dyspnea， early diagnosis，timely drug withdrawal，and symptomatic treatment measures such as glucocorticoid should be taken to ensure medication safety.

OBJECTIVE: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification. METHODS: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. RESULTS: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G₁-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway. CONCLUSION Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation ; Matrix Metalloproteinase 9 ; Molecular Docking Simulation ; Cell Cycle ; ErbB Receptors ; Apoptosis ; Colorectal Neoplasms/pathology* ; Cell Line, Tumor

Objective:To explore whether multi-parametric MRI (mpMRI) combined with 68Ga-prostate specific membrane antigen (PSMA) PET/CT can improve the detection efficiency of clinically significant prostate cancer (csPCa). Methods:Clinical and imaging data of 152 patients (age (68.5±8.5) years) who underwent mpMRI and 68Ga-PSMA PET/CT examination for suspected prostate cancer in the First Affiliated Hospital of the Air Force Medical University from January 2021 to November 2022 were retrospectively analyzed, with the histopathological results from transrectal ultrasound guided biopsy as reference. Lesions with Gleason scores (GS) ≥3+ 4 from the biopsy were diagnosed with csPCa, and lesions with negative biopsy or GS 6 were diagnosed with non-csPCa. MpMRI was evaluated independently by two radiologists according to the Prostate Imaging Reporting and Data System (PI-RADS) version 2.1. The radioactive uptake of 68Ga-PSMA PET/CT in prostate lesions was evaluated by SUV max. The independent-sample t test, Mann-Whitney U test and χ2 test were used to compare differences between the two groups, and then multivariate logistic regression analysis was performed. ROC curves analysis was used to analyze the diagnostic efficacies of individual and combined factors and Delong test was used. Results:There were 85 csPCa and 67 non-csPCa confirmed. Prostate specific antigen (PSA), PI-RADS score and SUV max were significantly different between the csPCa group and the non-csPCa group ( χ2=68.06, U values: -7.66, -8.98, all P<0.001). Multivariate logistic regression analysis indicated that PI-RADS score (odds ratio ( OR)=3.424, 95% CI: 1.651-7.100) and SUV max ( OR=1.931, 95% CI: 1.403-2.658) were independent predictors of csPCa (both P<0.001). ROC curves analysis revealed that the cut-off value for diagnosing csPCa was 4 for PI-RADS score and 5.6 for SUV max. The accuracy of mpMRI and PET/CT alone in csPCa diagnosis was 80%(122/152) (AUC of 0.789(95% CI: 0.711-0.866) with the sensitivity and specificity of 91%(77/85) and 67%(45/67)), and 87%(132/152) (AUC of 0.876(95% CI: 0.817-0.936) with the sensitivity and specificity of 81%(69/85) and 94%(63/67)), respectively. Several joint models incorporating 68Ga-PSMA PET/CT with mpMRI data were investigated, the model of PI-RADS 5 or PI-RADS 3-4 and SUV max>5.6 showed better performance than mpMRI and PET/CT alone and other joint models ( z values: 2.01-3.64, all P<0.05), with the accuracy of 91%(138/152) (AUC of 0.910(95% CI: 0.857-0.962) with the sensitivity and specificity of 89%(76/85) and 93%(62/67)). Conclusion:MpMRI combined with 68Ga-PSMA PET/CT can significantly improve the detection efficiency of csPCa, with the principal effect being improved in risk stratification of PI-RADS 3-4 lesions in mpMRI.

AIM To investigate the protective effects and the mechanism of the Liuwei Dihuang Pills on mouse brain microvascular endothelial(bEnd.3)cells damaged by β-Amyloid protein1-40(Aβ1-40).METHODS CCK8 method was used to detect the effects of Aβ1-40 and medicated serum of Liuwei Dihuang Pills(MSLDP)on cell activity,and to screen the appropriate concentration.bEnd.3 cells of the control group,the Aβ1-40 group,the MSLDP+Aβ1-40 group and the MSLDP group had their low density lipoprotein-associated protein 1(LRP1),receptor for advanced glycation end products(RAGE),matrix metalloproteinase-2(MMP-2),MMP-9,scaffold protein zonule protein-1(ZO-1)detected by Western blot.bEnd.3 cells assigned into the control group,the Aβ1-40 group,the FPS-ZM1(RAGE inhibitor)+Aβ1-40 group and the FPS-ZM1+Aβ1-40+MSLDP group had their expressions of RAGE,MMP-9,MMP-2 and ZO-1 detected by Western blot as well.RESULTS The cell activity of bEnd.3,was dose-dependently decreased by Aβ1-40(P<0.01),but was protected by MSLDP(P<0.05,P<0.01).And 10 μmol/L Aβ1-40 and 10%MSLDP were selected for subsequent experiments.Compared with the control group,the Aβ1-40 group displayed increased protein expressions of RAGE,MMP-2 and MMP-9(P<0.01),decreased protein expressions of LRP1,ZO-1 and BDNF(P<0.05,P<0.01),and decreased fluorescence intensities of LRP1 and ZO-1(P<0.01).Compared with the Aβ1-40 group,the MSLDP group shared decreased expressions of RAGE,MMP-2,MMP-9 proteins and RAGE fluorescence intensity(P<0.05,P<0.01),and increased expressions of LRP1,ZO-1 and BDNF proteins,and the fluorescence intensity of LRP1 and ZO-1(P<0.05,P<0.01);the Aβ1-40+FPS-ZM1 group displayed decreased protein expressions of MMP-2,MMP9 and RAGE(P<0.05,P<0.01),and increased ZO-1 protein expression(P<0.05);and the Aβ1-40+FPS-ZM1+ MSLDP group displayed an even more decreased protein expressions of MMP-2,MMP9 and RAGE(P<0.01),increased ZO-1 protein expression(P<0.01)due to the the combination use of FPS-ZM1 and MSLDP.CONCLUSION Liuwei Dihuang Pills can protect the tight junction of bEnd.3 injured by Aβ1-40 and neurovascular units from Alzheimer's disease by alleviating the dysfunction of the blood-brain barrier via RAGE-mediated MMP-2/MMP-9 pathway inhibition.

Purpose::Although traditional craniotomy (TC) surgery has failed to show benefits for the functional outcome of intracerebral hemorrhage (ICH). However, a minimally invasive hematoma removal plan to avoid white matter fiber damage may be a safer and more feasible surgical approach, which may improve the prognosis of ICH. We conducted a historical cohort study on the use of multimodal image fusion-assisted neuroendoscopic surgery (MINS) for the treatment of ICH, and compared its safety and effectiveness with traditional methods.Methods::This is a historical cohort study involving 241 patients with cerebral hemorrhage. Divided into MINS group and TC group based on surgical methods. Multimodal images (CT skull, CT angiography, and white matter fiber of MRI diffusion-tensor imaging) were fused into 3 dimensional images for preoperative planning and intraoperative guidance of endoscopic hematoma removal in the MINS group. Clinical features, operative efficiency, perioperative complications, and prognoses between 2 groups were compared. Normally distributed data were analyzed using t-test of 2 independent samples, Nonnormally distributed data were compared using the Kruskal-Wallis test. Meanwhile categorical data were analyzed via the Chi-square test or Fisher’s exact test. All statistical tests were two-sided, and p < 0.05 was considered statistically significant. Results::A total of 42 patients with ICH were enrolled, who underwent TC surgery or MINS. Patients who underwent MINS had shorter operative time ( p < 0.001), less blood loss ( p < 0.001), better hematoma evacuation ( p =0.003), and a shorter stay in the intensive care unit ( p =0.002) than patients who underwent TC. Based on clinical characteristics and analysis of perioperative complications, there is no significant difference between the 2 surgical methods. Modified Rankin scale scores at 180 days were better in the MINS than in the TC group ( p =0.014). Conclusions::Compared with TC for the treatment of ICH, MINS is safer and more efficient in cleaning ICH, which improved the prognosis of the patients. In the future, a larger sample size clinical trial will be needed to evaluate its efficacy.