Objective: To investigate the urban and rural differences in adverse outcomes of pulmonary tuberculosis (PTB) in patients with pulmonary tuberculosis-diabetes mellitus comorbidity (PTB-DM), so as to provide insights into improving the prevention and treatment measures for PTB-DM. Methods: Patients with PTB-DM who were admitted and discharged from 14 designated tuberculosis hospitals in Hangzhou City from 2018 to 2022 were selected. Basic information, and history of diagnosis and treatment were collected through hospital information systems. The adverse outcomes of PTB were defined as endpoints, and the proportions of adverse outcomes of PTB in urban and rural patients with PTB-DM were analyzed. Factors affecting the adverse outcomes of PTB were identified using a multivariable Cox proportional hazards regression model. Results: A total of 823 patients with PTB-DM were enrolled, including 354 (43.01%) urban and 469 (56.99%) rural patients. There were 112 (13.61%) patients with adverse outcomes of PTB. The proportions of adverse outcomes of PTB in urban and rural patients were 14.41% and 13.01%, respectively, with no statistically significant difference (P>0.05). Multivariable Cox proportional hazards regression analysis identified first diagnosed in county-level hospitals or above (HR=2.107, 95%CI: 1.181-3.758) and drug resistance (HR=3.303, 95%CI: 1.653-6.600) as the risk factors for adverse outcomes of PTB in urban patients with PTB-DM, while the treatment/observed management throughout the process (HR=0.470, 95%CI: 0.274-0.803) and fixed-dose combinations throughout the process (HR=0.331, 95%CI: 0.151-0.729) as the protective factors for adverse outcomes in rural patients with PTB-DM. Conclusions There are differences in influencing factors for adverse outcomes of PTB in urban and rural patients with PTB-DM. The adverse outcomes of PTB are associated with first diagnosed hospitals and drug resistance in urban patients, and are associated with the treatment/observed management and fixed-dose combinations throughout the process in rural patients.

Depressive disorder is a mental illness characterized by poor mood and cognitive dysfunction caused by a range of complicated factors. Antidepressants have strong short-term efficacy in clinical application, yet with significant adverse effects and resistance in long-term use. Essential oils are small molecular compounds mainly composed of monoterpenes and sesquiterpenes, most of which are characterized by aromatic odors, easy permeability through the blood-brain barrier, and low toxic side effects. Volatile oil from traditional Chinese medicine can regulate neurotransmitter monoamine, hypothalamic-pituitary-adrenal axis, brain-derived neurotrophic factor, neuroinflammation and oxidative stress, and intestinal microbiota-gut-brain axis to exert an antidepressant effect through multiple pathways and targets. This review summarizes the main antidepressant chemical components of essential oil of traditional Chinese medicine, their pharmacological mechanisms and clinical application, aiming to provide some reference for further development and clinical application of essential oil of traditional Chinese medicine.

BACKGROUND: The level of measurable residual disease (MRD) before and after transplantation is related to inferior transplant outcomes, and post-hematopoietic stem cell transplantation measurable residual disease (post-HSCT MRD) has higher prognostic value in determining risk than pre-hematopoietic stem cell transplantation measurable residual disease (pre-HSCT MRD). However, only a few work has been devoted to the risk factors for positive post-HSCT MRD in patients with acute lymphoblastic leukemia (ALL). This study evaluated the risk factors for post-HSCT MRD positivity in patients with ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 1683 ALL patients from Peking University People's Hospital between January 2009 and December 2019 were enrolled to evaluate the cumulative incidence of post-HSCT MRD. Cox proportional hazard regression models were built for time-to-event outcomes. Multivariable analysis was performed to determine independent influencing factors from the univariable analysis. RESULTS: Both in total patients and in T-cell ALL or B-cell ALL, pediatric or adult, human leukocyte antigen-matched sibling donor transplantation or haploidentical SCT subgroups, positive pre-HSCT MRD was a risk factor for post-HSCT MRD positivity ( P  <0.001 for all). Disease status (complete remission 1 [CR1] vs . ≥CR2) was also a risk factor for post-HSCT MRD positivity in all patients and in the B cell-ALL, pediatric, or haploidentical SCT subgroups ( P  = 0.027; P  = 0.003; P  = 0.035; P  = 0.003, respectively). A risk score for post-HSCT MRD positivity was developed using the variables pre-HSCT MRD and disease status. The cumulative incidence of post-HSCT MRD positivity was 12.3%, 25.1%, and 38.8% for subjects with scores of 0, 1, and 2-3, respectively ( P  <0.001). Multivariable analysis confirmed the association of the risk score with the cumulative incidence of post-HSCT MRD positivity and relapse as well as leukemia-free survival and overall survival. CONCLUSION Our results indicated that positive pre-MRD and disease status were two independent risk factors for post-HSCT MRD positivity in patients with ALL who underwent allo-HSCT.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology* ; Neoplasm, Residual ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; Risk Factors ; Adolescent ; Adult ; Child ; Child, Preschool ; Young Adult ; Middle Aged ; Infant ; Transplantation, Homologous ; Proportional Hazards Models ; Retrospective Studies

ObjectiveTo explore the underlying mechanism by which the Chinese medicine compound Yitangkang granule（YTK） treats diabetic kidney disease （DKD） by observing its effects on podocyte autophagy through the regulation of phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/forkhead transcription factor O1 （FoxO1） signaling pathway mediated by silent information regulator 1 （SIRT1） via advanced glycation end products （AGE）/receptor for AGE （RAGE） axis. MethodNinety-six 8-week-old healthy male SPF-grade Wistar rats were selected and randomly divided into blank control group （B）， model control group， high-dose YTK （40 g·kg^-1）， medium-dose YTK （20 g·kg^-1）， low-dose YTK （10 g·kg^-1）， and Western medicine control （20 mg·kg^-1 losartan） groups. The DKD rat model was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin. After successful modeling， the rats in each group received the corresponding treatments for eight weeks. The levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， and catalase （CAT） were measured according to the instructions of the respective assay kits. Hematoxylin and eosin （HE） staining was used to observe pathological changes in kidney tissues. Immunohistochemistry was employed to detect the average optical density values of α-smooth muscle actin （α-SMA）， fibronectin （FN）， desmin， and nephrin. Western blot analysis was used to measure the expression levels of PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， RAGE， SIRT1， Caspase-3， and FoxO1 proteins in kidney tissues of DKD rats. ResultCompared with the blank control group， the model group showed significantly lower levels of SOD， GSH-Px， and CAT， and significantly higher levels of MDA （P<0.01）. The rats exhibited severe kidney damage. The positive expression of podocyte marker proteins α-SMA， FN， and desmin increased significantly， while nephrin and podocin significantly decreased （P<0.01）. The expression levels of PI3K， p-PI3K， Akt， p-Akt， RAGE， and Caspase-3 proteins were significantly elevated， while SIRT1 and FoxO1 protein levels were significantly reduced （P<0.01）. Compared with the model control group， rats in the YTK treatment groups showed significantly higher levels of SOD， GSH-Px， and CAT， and significantly lower levels of MDA in serum （P<0.01）. The degree of kidney damage was reduced to varying extents. The average optical density values of podocyte marker proteins α-SMA， FN， and desmin were significantly decreased， while nephrin and podocin significantly increased （P<0.01）. The expression levels of PI3K， p-PI3K， Akt， p-Akt， RAGE， and Caspase-3 in kidney tissues were significantly reduced， while SIRT1 and FoxO1 expression levels significantly increased （P<0.01）. The Chinese medicine groups demonstrated a clear dose-response trend. ConclusionYTK may alleviate kidney pathological damage， reduce proteinuria， and protect kidney function in DKD rats， thereby delaying the progression of DKD by improving podocyte autophagy through the AGE-RAGE axis-mediated SIRT1 regulation of the PI3K/Akt/FoxO1 signaling pathway. Additionally， a dose-response relationship was observed in the Chinese medicine groups.

Objective: To explore the current status of knowledge, attitudes and practices (KAP) regarding tuberculosis(TB)prevention and control among high school students, and to compare differences between male and female students, so as to provide a scientific basis for targeted TB prevention and control measures in high schools. Methods: From April to May 2024, a stratified cluster random sampling method was employed to conduct an electronic questionnaire survey among 1 912 students from 10 high schools using a compiled questionnaire on KAP towards TB prevention and control. The AMOS 26.0 software was utilized to construct structural equation modeling (SEM) and compared the difference among genders. Results: The overall awareness rate of core TB knowledge among high school students in Gongshu District was 76.62%. Additionally, core knowledge about TB (6.28±1.44), prevention attitudes (6.02±1.84), and prevention practices (6.38±2.11) scores of female students were higher than those of male students (5.96±1.74, 5.59±2.21, 6.15±2.23) ( t =4.31, 4.64, 2.25, P <0.05). The SEM showed that knowledge had a strong positive impact on practices and attitudes among boys, with total effect values of 0.963 and 0.819 , respectively; while the positive influence of attitudes on practices was relatively weak, with a total effect value of 0.186. Among girls, attitudes had a positive impact on practices and knowledge, with total effect values of 0.479 and 0.222, respectively. Conclusions The pathways and strengths of influence of KAP in the SEM of TB prevention and control differ between male and female high school students. Therefore, differentiated strategies should be implemented for TB health education targeting male and female high school students.

Humans ; Nephrotic Syndrome ; Hematopoietic Stem Cell Transplantation ; Tissue Donors ; Transplantation Conditioning ; Graft vs Host Disease

Objective To develop a GPU-based Monte Carlo dose calculation module for helical tomotherapy(TOMO),and integrate it into the commercial software ArcherQA to achieve fast and accurate dose verification in clinic.Methods The TOMO treatment head was modeled using TOPAS to obtain phase space files,and a fast weight tuning algorithm was used to simulate particle transport in multi-leaf collimator for improving computational efficiency,and finally,GPU-based Monte Carlo algorithms in ArcherQA were used to simulate particle transport in patients.To verify the model accuracy,the ArcherQA calculated results in water tank were compared with measured data for different open fields.In addition,multiple comparisons among ArcherQA results,TPS results and ArcCHECK results were conducted on 15 clinical cases(5 cases in the head and neck,5 cases in the chest and abdomen,and 5 cases in the whole body).Results In the water tank tests for 40 cm×5.0 cm,40 cm×2.5 cm and 40 cm× 1.0 cm radiation fields,the average global relative errors of the percentage depth dose,transverse dose distribution,and longitudinal dose distribution calculated by ArcherQA with the corresponding measured values were 0.72％,0.66％,and 0.54％,respectively.Over 98％of the voxels had a global relative error of less than 1％.As for 15 clinical cases,in 2％/2 mm criteria,the mean Gamma passing rate was 98.1％between ArcherQA and TPS,99.1％between TPS and ArcCHECK,and 99.4％between ArcherQA and ArcCHECK.The uncertainty of the simulation maintained less than 1％,and the average time taken for calculation based on patient CT vs ArcCHECK phantom was 87 s vs 64 s.Conclusion ArcherQA can be used for independent dose validation for TOMO plans for it can provide fast and accurate dose calculations.

In recent years, with the wide application of immune checkpoint inhibitors, the landscape of non small cell lung cancer has changed dramatically. Immune checkpoints like programmed death protein/ligand 1(PD-1/PD-L1), cytotoxic T lymphocyte associated antigen-4(CTLA-4) are negative regulators of T-cell immune response. Inhibition of these immune checkpoints can further activate the immune system and promote anti-tumor response. Compared to the limited efficacy of monotherapy, reasonable dual immunotherapy shows great benefit at different stages of anti-tumour immunity. This article aims to comprehensively review the mechanism, treatment regimen and the latest clinical progress of dual immunotherapy so as to provide more precise and individualised immunotherapy for NSCLC patients.