OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Objective To assess the situation and influencing factors of occupational burnout among the staff at the Center for Disease Control and Prevention (CDC) in Sichuan Province. Methods A total of 1 038 CDC staff members in Sichuan Province were selected as the study subjects using the stratified random sampling method. Occupational burnout of the staff was assessed using the Maslach Burnout Inventory General Survey via an online questionnaire. Results The detection rate of occupational burnout was 42.3% (439/1 038). Binary logistic regression analysis result showed that, after controlling for confounding factors such as education level and alcohol consumption, CDC staffs aged at 20-<31, 31-<41, and 41-<51 years were at higher risk of occupational burnout compared with those ≥51 years (all P<0.05). CDC staffs with 5-<10 or ≥10 years of service had higher occupational burnout risk compared with those with <5 years (both P<0.05). CDC staffs with poor or fair health status, irregular diet, and poor sleep quality had higher risk of occupational burnout compared with those healthy, have regular diet, and good sleep quality (all P<0.05). The risk of occupational burnout increased with higher overtime frequency (all P<0.05). Conclusion Occupational burnout among CDC staffs in Sichuan Province is relatively high. Age, years of service, health status, diet, sleep quality, and overtime frequency are key influencing factors.

This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Plant Leaves/chemistry*

OBJECTIVE: To investigate the clinical characteristics and prognosis of primary pulmonary lymphoma (PPL). METHODS: The clinical data of 17 patients with PPL admitted to Gansu Provincial Hospital from January 2013 to June 2023 were collected, and their clinical characteristics and prognosis were retrospectively analyzed and summarized. RESULTS: The median age of the 17 patients was 56 (29-73) years old. There were 8 males and 9 females. According to Ann Arbor staging system, there were 9 patients with stage I-II and 8 patients with stage III-IV. There were 14 patients with IPI score of 0-2 and 3 patients with IPI score of 3-4. All 17 patients had symptoms at the initial diagnosis, most of the first symptoms were cough, and 6 patients had B symptoms.Among the 17 patients, there were 8 cases of diffuse large B-cell lymphoma (DLBCL), 5 cases of mucosa-associated lymphoid tissue (MALT) lymphoma, 1 case of gray zone lymphoma (GZL), and 3 cases of Hodgkin's lymphoma (HL). 15 patients received chemotherapy, of which 3 cases received autologous hematopoietic stem cell transplantation(ASCT) and 3 cases received radiotherapy; 2 patients did not receive treatment. The median number of chemotherapy courses was 6(2-8). The short-term efficacy was evaluated, 12 patients achieved complete remission (CR) and 3 patients achieved partial remission (PR). The age, pathological subtype, sex, Ann Arbor stage, β₂-microglobulin(β₂-MG) level, lactate dehydrogenase(LDH) level were not correlated with CR rate (P >0.05), while IPI score was correlated with recent CR rate (P < 0.05 ). The median follow-up time was 31(2-102) months. One of the 12 CR patients died of COVID-19, and the rest survived. Among the 3 patients who did not reach CR, 1 died after disease progression, while the other 2 survived. One of the 2 untreated patients died one year after diagnosis. Both the median progression-free survival (PFS) time and overall survival (OS) time of the 17 patients were both 31 (2-102) months. CONCLUSION The incidence of PPL is low, and the disease has no specific clinical manifestations, which is easily missed and misdiagnosed. The pathological subtypes are mainly MALT lymphoma and DLBCL, and the treatment is mainly combined chemotherapy. The IPI score is related to the treatment efficacy.
Humans ; Middle Aged ; Male ; Female ; Adult ; Prognosis ; Aged ; Lung Neoplasms/therapy* ; Retrospective Studies ; Neoplasm Staging ; Lymphoma/therapy* ; Lymphoma, Large B-Cell, Diffuse

Platelet transfusion refractoriness (PTR) is a common issue among patients with hematological diseases and tumors. This article reviews the diagnostic criteria, influencing factors, and recent prevention and management strategies for immune PTR. The diagnostic criteria typically involve post-transfusion platelet increment (PI), platelet recovery rate (PPR), and corrected count increment (CCI). Both immune and non-immune factors can lead to PTR, with immune factors mainly including HLA and HPA antibodies. Prevention and management strategies include the use of leukocyte-reduced platelets, HLA and HPA antigen-matched platelets, intravenous immunoglobulin therapy, and immunosuppressive strategies. Although various strategies have been proposed and applied in clinical practice, the prevention and management of immune PTR remain challenging. Future research needs to explore more effective individualized treatment strategies, while also considering the potential application of emerging technologies such as nanotechnology in the field of transfusion.

Background: Aristolochic acid II (AAII), a major nephrotoxic and carcinogenic component of aristolochic acids (AAs), has been less studied compared with its well-characterized analog, aristolochic acid I (AAI). Although AAs are known to induce carcinogenesis via DNA adduct formation, the toxicity mechanisms, environmental prevalence, and long-term health impacts of AAII remain poorly understood. Objective: This study aimed to systematically evaluate AAII’s acute and chronic toxicity, carcinogenic mechanisms, and environmental exposure patterns using integrated murine models and phytochemical analyses to clarify its toxicological profile and associated health risks. Methods: C57BL/6J mice were used in the following experiments: (1) determination of AAII content in 3 commonly used Aristolochia medicinal materials via liquid chromatography-mass spectrometry/mass spectrometry; (2) acute toxicity testing with single doses of 10, 20, or 40 mg/kg; and (3) chronic exposure with 1 or 10 mg/kg administered every other day for 24 weeks, followed by 21 to 40 weeks of postexposure monitoring. Histopathological examination, whole-exome sequencing, biochemical assays, and micronucleus tests were performed to assess multi-organ damage, tumorigenesis, genomic mutation signatures, and direct clastogenicity. Phytochemical analyses were used to evaluate environmental distribution. Results: (1) A single 40 mg/kg dose of AAII induced dose-dependent renal tubular degeneration without hepatotoxicity; (2) the 10 mg/kg group showed significant mortality (20%), tumor incidence (33.3%, primarily forestomach and bladder transitional cell carcinomas), persistent renal interstitial fibrosis, and subclinical hepatic injury. Chronic exposure to 1 mg/kg still induced 13.3% mortality and 15.5% tumor incidence over a 64-week period; (3) whole-exome sequencing revealed a predominance of C>T mutations and pathway enrichment in chemical carcinogenesis and cytochrome P450-mediated metabolism, indicating reactive metabolite-driven mechanisms distinct from classical AA-DNA adducts; and (4) no histopathological changes were observed in nontarget organs (brain, heart, and testes), and micronucleus assays confirmed the absence of direct clastogenicity. Conclusion: This study highlights the delayed carcinogenic risks of low-dose chronic AAII exposure and emphasizes the need to update regulatory frameworks to ensure the safe use of aristolochiaceae-containing herbal products.

Objective:To investigate the effect and mechanism of injectable photopolymerizable porous gelatin methacrylate anhydride (Porous GelMA)/methacrylated silk fibroin (SilMA) composite hydrogel (PSE) loaded with human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) in promoting knee joint cartilage regeneration.Methods:The porous GelMA solution (60 g/L) was mixed with SilMA solution (200 g/L) at a volume ratio of 6∶1 . The mixture was ultraviolet-irradiated for 30 seconds to form a cured Porous GelMA/SilMA hydrogel (P/S6). The hUCMSC-Exos was isolated via differential centrifugation coupled with ultrafiltration and then was incorporated into the Porous GelMA/SilMA composite solution at 200 μg/ml, followed by ultraviolet irradiation for 30 seconds to generate Exos-loaded PSE. Primary rat chondrocytes (P1) were divided into control group, P/S6 group, and PSE group to characterize the porosity, compressive strength, and sustained exosome release kinetics of PSE hydrogel. Chondrocytes were allocated to control group, interleukin-1β (IL-1β) group, P/S6 group, and PSE group, among which the last three groups were preconditioned with 10 ng/ml IL-1β for 24 hours, and then cultured in complete medium, P/S6 extract and PSE extract for 3 days, respectively, to establish in vitro cartilage defect models, while the control group remained untreated. Western blot and qRT-PCR analysis were conducted to quantify the expression levels of antibody to aggrecan core protein (ACAN), sex-determining region Y-box transcription factor 9 (SOX9), matrix metalloproteinase-13 (MMP13) and collagen type II (COL II). Murine monocyte-macrophage leukemia cells (RAW264.7) were divided into control group, P/S6 group, and PSE group, which were then cultured in complete medium, PSE extract, and PSE extract medium for 3 days, respectively. qRT-PCR was employed to detect the expression levels of recombinant arginase-1 protein (ARG1), mannose receptor (CD206), and inducible nitric oxide synthase (iNOS). Transcriptomic sequencing was used to identify differentially expressed genes during PSE-mediated chondrocyte regeneration, followed by functional enrichment analysis of key signaling pathways. Twenty-four SD rats were selected to establish cartilage defect models and assigned to injury control group, P/S6 group, and PSE group according to the random number table (8 rats per group). The right knee joints of the rats were surgically exposed, and cylindrical osteochondral defects (a diameter of 2.0 mm× a depth of 1.0 mm) were surgically created in the center of the femoral trochlear groove using a drill bit. The injury control group received phosphate-buffered saline, while the P/S6 group and PSE group were injected with corresponding hydrogels followed by photo-crosslinking. Incisions then were closed in layers. At 6 and 10 weeks after injury, specimens were harvested for HE staining and safranin O-fast green staining to evaluate cartilage regeneration and immunohistochemistry staining to quantify the positive area fractions for COL II, MMP13, ARG1, and CD206 in the defect areas. Results:PSE hydrogel exhibited compressive strength matching native cartilage (0.41 MPa), high porosity (85%), and sustained exosome release capacity (cumulative release rate of approximately 85% over 14 days). In chondrocyte repair experiments, compared to the IL-1β group, the PSE group demonstrated significantly upregulated expression of anabolic markers of cartilage (COL II expression increased by 2.1-fold, ACAN by 1.8-fold, and SOX9 by 1.5-fold) ( P<0.01) as well as significantly suppressed expression of catabolic markers (MMP13 expression decreased by 52%) ( P<0.01). In macrophage polarization assays, the PSE group exhibited ARG1 expression increased by 68% when compared to the control group ( P<0.01), thus promoting M2 polarization of macrophages. Transcriptomic analysis revealed that PSE enhanced extracellular matrix (ECM) synthesis by activating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway and ECM-receptor interaction pathway, as well as by suppressing inflammation-related gene expression. Histological evaluation in animal experiments revealed regeneration of hyaline cartilage with smooth, continuous surfaces in the defect areas in the PSE group. At 10 weeks after surgery, the neocartilage-positive area in the PSE group was (9.94±0.26)%, significantly larger than (1.67±0.11)% in the injury control group ( P<0.01). Besides, the CD206? M2 macrophage-positive area reached (14.44±0.23)% in the PSE group, significantly larger than (3.41±0.36)% in the injury control group ( P<0.01). Conclusions:The PSE hydrogel successfully engineered in the study can significantly promote regenerative repair of knee cartilage defects through a dual mechanism of enhanced ECM anabolism and remodeled inflammatory microenvironment. The core mechanisms involve specific activation of the PI3K/Akt pathway (boosting chondrocyte proliferation and survival) and ECM-receptor interaction pathway (driving ECM synthesis and assembly) by exosome-loaded PSE, while effectively polarizing macrophages toward an anti-inflammatory M2 phenotype so as to coordinately regulate cartilage ECM metabolism and suppress inflammatory responses.

Colorectal adenoma is a definite precancerous lesion,and the"inflammation-cancer transformation"is a key pathological link in the process of colorectal adenoma-cancer evolution.Under the guidance of the theory of"preventive treatment of diseases"in TCM,prevention before disease onset and preventing the development of the occurred disease has become the consensus and the important subject of clinical research to block the"inflammation-cancer transformation"and prevent the precancerous lesions of colorectal cancer.This article discussed the effectiveness of TCM in preventing and treating the"inflammation-cancer transformation"from different aspects.Its advantages are reflected in improving the symptoms of TCM and improving the quality of life,etc.Its mechanism may be related to inhibiting the activation of cancer-promoting signals,regulating inflammation,maintaining intestinal microbial homeostasis,and protecting the intestinal barrier.By explaining the pathogenesis of adenoma-cancer transformation in TCM,this article discussed the efficacy and advantages of TCM to block"inflammation-cancer transformation",analyzed its intervention targets and pathways,providing references for the intervention of TCM in the management of precancerous lesions of colorectal cancer and the synergistic prevention and treatment of traditional Chinese and Western medicine.