ObjectiveTo investigate the mechanism of Yangxin Tongmai Formula （养心通脉方， YTF） in trea-ting coronary heart disease with blood stasis syndrome based on DNA methylation. MethodsSeventy-two SD rats were randomly divided into a control group （n=12） and a modeling group （n=60）. The modeling group was subjected to a high-fat diet， intragastric administration of vitamin D3， and subcutaneous injection of isoprenaline to establish the rat model of coronary heart disease with blood stasis syndrome. Forty-one successfully modeled rats were then randomly allocated into model group， YTF low-， medium-， and high-dose groups， and the atorvastatin calcium group， with 8 rats in each group and 1 rat reserved. The YTF low-， medium-， and high-dose groups received YTF at 6， 12， and 18 g/（kg·d） by gavage， respectively. The atorvastatin calcium group received atorvastatin calcium tablets at 1.8 mg/（kg·d） by gavage. The control group and the model group received 0.9% sodium chloride injection at 4 ml/（kg·d） by gavage. All administrations were performed once daily for 3 weeks. Twenty-four hours after the last administration， serum lipid levels including total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C）， myocardial enzymes including cardiac troponin T （cTnT）， creatine kinase MB （CK-MB）， and lactate dehydrogenase （LDH）， and inflammatory factors including interleukin-1β （IL-1β） and interleukin-10 （IL-10） were detected by ELISA. Pathological changes in myocardial tissue were observed via HE staining. Whole blood DNA methylation sequencing was used to analyze differential methylation gene expression among the control group， model group， and YTF high-dose group. Western Blotting was used to verify the protein levels of the key genes and downstream signaling pathways. ResultsCompared to the control group， the model group showed increased levels of TC， TG， LDL-C， cTnT， CK-MB， LDH， and IL-1β， along with decreased levels of HDL-C and IL-10 （P＜0.05 or P＜0.01）. Compared to the model group， all treatment groups exhibited decreased levels of TC， LDL-C， CK-MB， and LDH， along with increased IL-10 levels. Among these， the high-dose YTF group demonstrated superior efficacy in reducing cTnT levels compared to the other TCM groups （P＜0.05 or P＜0.01）. HE staining indicated that the YTF high-dose group ameliorated myocardial cell swelling， disordered arrangement， pyknosis， and disappearance of nuclei， thereby reducing myocardial cell damage. Whole blood DNA methylation sequencing identified 240 differentially methylated genes shared by the control group， model group， and YTF high-dose group， including 109 hypermethylated and 131 hypomethylated genes； eif2ak3 was identified as a key differentially methylated gene. Compared to the control group， the model group exhibited increased protein levels of eukaryotic translation initiation factor 2 alpha kinase 3 （eIf2ak3）， phosphorylated protein kinase RNA-like endoplasmic reticulum kinase （p-PERK）， activating transcription factor 4 （ATF4）， C/EBP homologous protein （CHOP）， and Bax， along with a decreased level of B-cell lymphoma-2 （Bcl-2） protein （P＜0.05 or P＜0.01）. Compared to the model group， the YTF high-dose group showed decreased protein levels of eIf2ak3， p-PERK， ATF4， CHOP， and Bax， and an increased level of Bcl-2 protein （P＜0.05 or P＜0.01）. ConclusionYTF may regulate key differentially methylated genes such as eIf2ak3 and the PERK/ATF4/CHOP signaling pathway， thereby inhibiting endoplasmic reticulum stress， reducing myocardial cell apoptosis， and exerting therapeutic effects in coronary heart disease blood stasis syndrome.

To investigate the changes in peripheral blood immune cells before and after the onset of septic shock in patients with malignant tumors, and to analyze the relationship between these immune cells and patient prognosis.

Background Mitochondrial biogenesis is pivotal in coal workers' pneumoconiosis fibrosis, yet the role of the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-nuclear respiratory factor 1 (NRF1)-mitochondrial transcription factor A (TFAM) pathway inmitochondrial biogenesis remains elusive, warranting further investigation. Objective To elucidate the role of the PGC-1α-NRF1-TFAM pathway in mitochondrial biogenesis in a rat coal workers' pneumoconiosis model through in vivo and in vitro experiments. Methods (1)n vivo: twelve SPF male SD rats (200-220 g) were randomized into a control group and a coal dust group (n=6 per group). After acclimatization, the coal dust group received 1 mL 50 mg·mL⁻¹ coal dust suspension via intratracheal instillation; the controls received saline. Lung tissues were harvested after two months for histopathology [HE, Masson, and transmission electron microscopy (TEM) ], protein and mRNA analysis, and mitochondrial DNA (mtDNA) quantification by quantitative real-time polymerase chain reaction (qPCR). (2) In vitro: rat lung type II epithelial cells (RLE-6TN) cells were exposed to coal dust (50, 100, 200, and 400 mg·L⁻¹, 24 h). CCK-8 assay determined optimal doses. Ultrastructural changes were analyzed by TEM. Cells were transfected with OE-PGC-1α (PGC-1α overexpression) or shRNA-PGC-1α plasmids (PGC-1α knockdown), and the transfection efficiency was determined by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). The expression levels of alpah-smooth muscle actin (α-SMA), citrate synthase (CS), PGC-1α, NRF1, TFAM, and fibronectin (Fn) proteins and their corresponding mRNA were detected using Western blot and RT-qPCR, respectively. The relative content of mtDNA was determined by qPCR. Results In vivo: the control group lung samples exhibited soft, pink parenchyma, while the coal dust-exposed lungs showed blackened surfaces with soft texture. The histopathological evaluation revealed intact alveolar walls in the controls versus structural destruction, micro-nodules, and fibrotic areas in the coal dust group. After Masson staining, coal dust deposits were found surrounded by blue collagen fibers in the exposed lungs, but absent in the controls. The coal dust group displayed significant upregulation of fibrotic marker α-SMA and downregulation of mitochondrial biogenesis markers (CS, PGC-1α, NRF1, TFAM) and mtDNA compared to the controls (P<0.05). In vitro: coal dust exposure reduced cell density and induced morphological alterations. TEM revealed evenly distributed normal mitochondria in controls versus mitochondrial swelling, disrupted cristae, and reduced numbers in exposed cells. The mitochondrial biogenesis markers were elevated in the coal dust + OE-PGC-1α group compared to the coal dust + OE-NC group (P<0.05); in contrast, they were decreased in the coal dust + shRNA-PGC-1α group compared to the coal dust + shRNA-NC group (P<0.05). Compared to the control group, the expression levels of the fibrosis marker α-SMA mRNA and protein were increased in the coal dust group (P<0.05). Overexpression of PGC-1α reduced α-SMA expression, while downregulation of PGC-1α increased its expression (P<0.05). Conclusion Coal dust exposure induces mitochondrial dysfunction and pulmonary fibrosis in vivo and in vitro via the PGC-1α-NRF1-TFAM pathway dysregulation. Targeting this pathway may mitigate coal dust-induced fibrosis by restoring mitochondrial biogenesis.

The Guidelines for Occupational Hazard Assessment and Control of Active Pharmaceutical Ingredient in the Pharmaceutical Industry (T/WSJD 60—2024) is the first guiding standard in the field of health in China that focuses on occupational health protection for active pharmaceutical ingredient (API). It covers the general principles, work procedures, assessment methods, and control strategies for API occupational hazard assessment, providing practical guidance and recommendations for pharmaceutical enterprises to eliminate or reduce occupational health risks associated with API, improve working environment, and enhance refined management practices. This article interpreted and analyzed the background of standard establishment, formulation process, fundamental basis, and main content, to provide scientific and comprehensive technical support for occupational health managers in the pharmaceutical industry to better apply this standard.

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Objective To investigate the expression of serum microRNA(miR)-340-5p,miR-155-5p and their relationship with Th1/Th2 cytokines in patients with chronic hepatitis B.Methods A total of 128 pa-tients with chronic hepatitis B in this hospital from October 2021 to October 2023 were selected as the study group,and 96 healthy subjects from the hospital during the same period were selected as the control group.The expression levels of serum miR-340-5p and miR-155-5p were detected by fluorescence quantitative PCR(qPCR),and the expression levels of serum Th1/Th2 cytokines were detected by enzyme-linked immunosor-bent assay(ELISA).The relationship between miR-340-5p,miR-155-5p and Th1/Th2 cytokines was analyzed by Pearson method,and the influence of serum miR-340-5p and miR-155-5p on the occurrence of chronic HPV infection was analyzed by Logistic regression.Results Compared with the reference group,the serum levels of miR-340-5p,miR-155-5p,IL-4,and IL-13 in the study group decreased(P＜0.05),while the levels of IFN-γand IL-12 increased(P＜0.05).Serum miR-340-5p was negatively correlated with IFN-γ and IL-12(r=-0.315,-0.293,both P＜0.05),and positively correlated with IL-4 and IL-13(r=0.413,0.412,both P＜0.05).Serum miR-155-5p was negatively correlated with IFN-γ and IL-12(r=-0.406,-0.375,both P＜0.05),and positively correlated with IL-4 and IL-13(r=0.343,0.407,both P＜0.05).Serum miR-340-5p(OR=0.735,95％CI:Increased expression levels of 0.590-0.915)and miR-155-5p(OR=0.612,95％CI:0.416-0.900)were protective factors for the occurrence of chronic hepatitis B.IFN-γ(OR=1.652,95％CI:1.170-2.333)and IL-12(OR=1.063,95％CI:1.012-1.116)were risk factors for chronic hepatitis B(P＜0.05).Conclusion Serum miR-340-5p and miR-155-5p are usually low expressed in chronic hepatitis B patients,and they are negatively correlated with Th1 cytokine level and positively correlated with Th2 cytokine level.

Objective To construct a graded nursing program for exercise rehabilitation of children with hematopoietic stem cell transplantation(HSCT)and carry out a preliminary application,aiming to provide a basis for healthcare personnel to guide the exercise rehabilitation of children with HSCT.Methods Literature analysis and Delphi expert correspondence were used to construct a graded nursing program of exercise rehabilitation for children with HSCT.Through the convenience sampling method,children with HSCT in the hematology department of a tertiary-level children's hospital in Suzhou City were selected as the study subjects from June-December 2023,of which 26 children with HSCT from September-December 2023 served as an experimental group,and 23 children with HSCT from June-August 2023 as a control group.The experimental group was applied with the graded nursing program of exercise rehabilitation,and the control group was applied with the conventional nursing care.The comparison of cardiorespiratory fitness and adverse events between the 2 groups after 8 weeks of exercise intervention was conducted,and the adherence to the exercise intervention programme in the experimental group was recorded.Results The final constructed graded care program of exercise rehabilitation for children with HSCT included 6 primary indicators,20 secondary indicators,and 44 tertiary indicators.Finally,21 children in the experimental group and 23 children in the control group were included in the study.After the intervention,the 6 min walking distance of the experimental group increased compared with that of the control group,and the difference was statistically significant(P＜0.001).85.71％of children in the experimental group had good exercise compliance,and there was no adverse events in both groups.Conclusion The constructed graded nursing program of exercise rehabilitation for children with HSCT is scientific,reasonable,safe and feasible,which can improve the cardiorespiratory capacity of children with HSCT and provide the basis for their exercise rehabilitation.

Objective:To analyze the epidemiological characteristics and changing trends of elderly patients with drug-resistant pulmonary tuberculosis(DR-PTB)at Beijing Chest Hospital, Capital Medical University, in order to provide references for clinical prevention and treatment.Methods:Data were retrospectively collected from all DR-PTB cases hospitalized in the electronic medical record system of Beijing Chest Hospital from 2019 to 2023.The epidemiological characteristics including classification, gender, age, occupation and their changing trends among elderly DR-PTB patients were analyzed.Results:Among 1 981 hospitalized DR-PTB patients, 400(20.19%)were elderly[aged 60-92 years, mean(68.67±7.01)years], showing an overall increasing trend from 2019 to 2023.Mono-resistant PTB was the most common(198 cases, 49.50%), followed by multidrug-resistant PTB(170 cases, 42.50%), extensively drug-resistant PTB(21 cases, 5.25%), and polyresistant PTB(11 cases, 2.75%).Among the elderly DR-PTB patients, 287 cases(71.75%)were male, 200 cases(50.00%)were initial treatment cases, 377 cases(94.25%)were Han nationality, 165 cases(41.25%)were Beijing residents, 185 cases(46.25%)were employees of enterprises and institutions, 109 cases(27.25%)were farmers, 68 cases(17.00%)were unemployed individuals, 202 cases(50.50%)were pathogen-positive cases(smear and culture positive), and 228 cases(57.00%), 331 cases(82.75%), 196 cases(49.00%)were patients with comorbidities, complications, and extrapulmonary tuberculosis, respectively.There were no significant differences between elderly and non-elderly groups in ethnicity, treatment classification, or comorbidities(all P>0.05).However, significantly differences were found in gender ( χ2=12.718, P<0.001), occupation ( χ2=97.500, P<0.001), patient origin ( χ2=119.771, P<0.001), pathogen detection results ( χ2=10.101, P=0.001), and drug resistance patterns ( χ2=15.990, P=0.001).The proportion of elderly DR-PTB patients showed an overall increasing trend, with rises in females(25.64%-28.70%), unemployed individuals(7.69%-20.37%), other occupations(5.13%-19.40%), Han ethnicity(91.03%-99.07%), initial treatment(33.33%-57.41%), smear-negative but culture-positive cases(46.15%-53.70%), polyresistant PTB(1.28%-9.26%), and extensively drug-resistant PTB(1.28%-3.70%). Conclusions:Among elderly DR-PTB patients, the proportions of female, unemployed individuals and other occupations, initial treatment cases, smear-negative but culture-positive cases, polyresistant PTB, and extensively drug-resistant PTB are increasing annually.Future efforts should focus on targeted prevention and treatment for key populations to further reduce the rate of elderly DR-PTB.

Objective:To investigate the incidence, clinical management and influencing factors of late-onset neutropenia (LON) in children with primary nephrotic syndrome (PNS) after Rituximab (RTX) treatment.Methods:A retrospective case-control study was conducted.The clinical data of PNS children who received RTX treatment at the First Affiliated Hospital of Xiamen University from March 2020 to August 2024 and were followed up for at least 6 months were collected.The RTX regimen was a single dose of 375 mg/m 2 with a maximum dose of 500 mg, and an additional dose was administered when the reexamination showed that peripheral blood CD19 + B cells were ≥ 1% or nephrotic syndrome relapsed.The patients were divided into an LON group and a non-LON group according to the presence or absence of LON, and then a comparison was made between the groups.The cumulative incidence of LON was estimated by the Kaplan-Meier method.Univariate and multivariate Logistic regression methods were used to identify the influencing factors of LON.Receiver operating characteristic (ROC) curves were plotted to assess the value of each influencing factor for predicting LON. Results:A total of 65 PNS patients were included.The incidence of LON was 19.3%(27/140) after 140 RTX treatment courses, and the first LON appeared 95.0 (64.0, 115.0) days after RTX treatment.Forty-nine patients received repeated RTX treatment.The incidence rates of LON after the first course, the second course, and the third course of RTX were 27.7%(18/65), 10.2%(5/49), and 18.8%(3/16), respectively, with no statistically significant difference ( χ2=5.764, P>0.05). There was also no significant difference in the incidence of LON between patients taking and not taking combined immunosuppressive agents after RTX treatment [35.3%(6/17) vs.37.8%(17/45), χ2=0.033, P>0.05]. Compared with the non-LON group, the LON group had a higher incidence of infections [48.1%(13/27) vs.15.0%(17/113), χ2=14.17, P<0.01], but no serious outcomes were observed in both groups.Multivariate Logistic analysis suggested that the age at treatment with RTX was an independent risk factor for LON after RTX treatment ( OR=0.763, 95% CI: 0.592-0.982). The area under the ROC curve of the age at treatment with RTX for predicting LON was 0.767 (95% CI: 0.628-0.906), with an optimal cutoff of 6.6 years, a sensitivity of 70.6%, and a specificity of 80.0%. Conclusions:The incidence of LON in PNS children after RTX treatment may be underestimated.Children who develop LON are at a higher risk of infections, but the prognosis is favorable.The age at treatment with RTX≤6.6 years is an independent risk factor for LON in PNS children.Close monitoring of neutrophil counts should be emphasized in younger PNS patients receiving RTX therapy.

Objective:To investigate the effects of sampling methods on pathological assessment of resected non-small cell lung cancer (NSCLC) specimen with tumor maximum diameter >3 cm after neoadjuvant therapy.Methods:NSCLC patients with a large tumor (diameter >3 cm) that were resected after neoadjuvant therapy from June 2020 to July 2023 were retrospectively collected in the Department of Pathology, Shanghai Pulmonary Hospital, Shanghai, China. Sampling methods of the tumor bed were performed in accordance with the international and Chinese experts recommendations for resection specimens following neoadjuvant therapy (recommended sampling method, RSM), and all remaining tumor bed lesions were completely sampled after recommended sampling (complete sampling method, CSM). The difference of pathological response assessment of residual viable tumor (RVT) between RSM and CSM was examined.Results:A total of 90 cases were identified and analyzed, including 39 cases of squamous cell carcinoma and 51 cases of adenocarcinoma, treated with neoadjuvant therapy including chemotherapy in 22 cases (24.4%), targeted therapy in 14 cases (15.6%), and chemoimmunotherapy in 54 cases (60.0%). There were 62 males and 28 females with an average age of (62.7±17.9) years. The average tumor maximum diameter was 4.3 cm (range, 3.1-8.0 cm). The average number of sampled blocks was 8 blocks (range, 5 to 16) and 15 blocks (range, 8 to 36) per case by RSM and CSM, respectively. According to the definition of major pathological response (MPR) in which RVT is ≤10%, the numbers of patients with MPR were 34 cases by RSM and 30 cases by CSM, respectively. Four cases showed inconsistent RVT between the two methods, including one case of squamous cell carcinoma and three cases of adenocarcinoma. The RVT of the four inconsistent cases was 7%, 7%, 5% and 9% (MPR by RSM), and 15%, 15%, 15% and 20% (non-MPR by CSM), respectively. The kappa values of MPR consistency evaluated by the two sampling methods were 0.893 for all cases, 0.906 for squamous cell carcinoma cases and 0.751 for adenocarcinoma cases. According to MPR cut-off of 65% for invasive primary adenocarcinoma, 24 cases and 20 cases achieved MPR by RSM and CSM, respectively. Of the four inconsistent cases, the RVT by RSM was 60% in three cases and 65% in one case (MPR), whereas the RVT by CSM was 70% in three cases and 75% in one case (non-MPR). The kappa value of the two sampling methods was 0.741.Conclusions:There is high consistency between RSM and CSM in the pathological assessment of post-treatment responses in resected NSCLC specimens with tumor maximum diameter larger than 3 cm. When the percentage of RVT cells is close to MPR, re-evaluation of the specimen is required and CSM may be necessary to accurately evaluate the degree of pathological remission, assist in clinical postoperative treatment, and predict patient prognosis.