Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Objective To analyze the underestimated influencing factors of ductal carcinoma in situ(DCIS)detected by ultrasound-guided fine needle aspiration cytology(US-FNAC),and to construct and validate the nomogram prediction model.Methods A total of 105 patients with DCIS diagnosed by US-FNAC in Yixing Hospital of Traditional Chinese Medicine from January 2020 to June 2023 were retrospectively selected.All patients were female and aged 40-76 years.According to postoperative pathological results,they were assigned to underestimated group(n=27)and non-underestimated group(n=78).The clinical data of the patients were collected to analyze the influencing factors of the underestimation of DCIS,and a nomogram prediction model was constructed.The receiver operating characteristic curve(ROC)was drawn,and the area under the curve(AUC)was used to analyze the predictive efficacy of the prediction model for the underestimated risk of DCIS before operation.Results Univariate analysis showed that the proportions of palpable masses,tumor size>2 cm,microcalcification,and breast imaging reporting and data system(BI-RADS)4B-5 in the underestimated group were higher than those in the non-underestimated group(P<0.05).Binary logistic regression analysis showed that tumor size[(odds ratio,OR)=4.453,95%(confidence interval,C I):1.890-10.486],microcalcification(OR=3.079,95%CI:1.650-5.742),BI-RADS classification(OR=5.211,95%CI:2.528-10.740)were the independent risk factors for preoperative underestimation of DCIS(P<0.05).Internal validation of the nomogram prediction model based on the above factors showed that the C-index was 0.865(95%CI:0.785-0.952),and the correction curve for predicting the underestimation of DCIS was close to the ideal curve(P>0.05).ROC curve showed that the nomogram model had a sensitivity of 87.90%,a specificity of 88.60%,and an AUC of 0.895(95%CI:0.823-0.966).Conclusion Tumor size,microcalcification and BI-RADS classification are independent risk factors for preoperative underestimation of DCIS.The nomogram prediction model based on these factors can better evaluate the risk of preoperative underestimation of DCIS.

Objective To evaluate the effectiveness of active screening in improving the detection rate of carbape-nem-resistant Enterobacterales(CRE)in the intensive care units(ICUs).Methods From July 2023 to June 2024,active screening of rectal swab CRE was conducted on ICU patients in 10 hospitals.ICU patients who underwent ac-tive screening from July 2023 to June 2024 were selected as the study group,while those who did not undergo active screening from July 2022 to June 2023 were selected as the control group.Difference in CRE detection rates between the two groups of patients was compared.Results A total of 7 803 ICU patients were included in the study group,744 CRE strains were detected,with a detection rate of 9.53％,out of which 304 CRE strains were detected through routine detection(detection rate 3.90％),3 707 patients underwent active screen,440 CRE strains were detected(detection rate 11.87％).7 561 ICU patients were included in the control group,out of which 250 CRE strains were detected through routine detection,with a detection rate of 3.31％.There was a statistically significant difference in the overall detection rate of CRE between two groups of patients(x2=246.18,P＜0.001).In the study group,CRE detection rate of active screening(11.87％)was higher than that of routine detection(3.90％),with statistically significant difference(x2=264.26,P＜0.001).A total of 17 CRE strains were detected from the study group.The proportions of Klebsiella pneumoniae(80.92％vs 73.41％)and Serratia marcescens(2.30％vs0.23％)in the routine detection group were both higher than in the active screening group,while the proportion of Escherichia coli in the routine detection group was lower(8.22％vs 19.55％),all with statistically significant differences(all P＜0.05).Conclusion The prevalence of CRE in ICUs is relatively high,with a wide range of bac-terial species.Active screening can improve the detection rate of CRE.

Objective To evaluate the effectiveness of active screening in improving the detection rate of carbape-nem-resistant Enterobacterales(CRE)in the intensive care units(ICUs).Methods From July 2023 to June 2024,active screening of rectal swab CRE was conducted on ICU patients in 10 hospitals.ICU patients who underwent ac-tive screening from July 2023 to June 2024 were selected as the study group,while those who did not undergo active screening from July 2022 to June 2023 were selected as the control group.Difference in CRE detection rates between the two groups of patients was compared.Results A total of 7 803 ICU patients were included in the study group,744 CRE strains were detected,with a detection rate of 9.53％,out of which 304 CRE strains were detected through routine detection(detection rate 3.90％),3 707 patients underwent active screen,440 CRE strains were detected(detection rate 11.87％).7 561 ICU patients were included in the control group,out of which 250 CRE strains were detected through routine detection,with a detection rate of 3.31％.There was a statistically significant difference in the overall detection rate of CRE between two groups of patients(x2=246.18,P＜0.001).In the study group,CRE detection rate of active screening(11.87％)was higher than that of routine detection(3.90％),with statistically significant difference(x2=264.26,P＜0.001).A total of 17 CRE strains were detected from the study group.The proportions of Klebsiella pneumoniae(80.92％vs 73.41％)and Serratia marcescens(2.30％vs0.23％)in the routine detection group were both higher than in the active screening group,while the proportion of Escherichia coli in the routine detection group was lower(8.22％vs 19.55％),all with statistically significant differences(all P＜0.05).Conclusion The prevalence of CRE in ICUs is relatively high,with a wide range of bac-terial species.Active screening can improve the detection rate of CRE.

Tacrolimus is a crucial therapeutic drug for preventing immune rejection after solid organ transplantation in children.Due to the narrow treatment window and significant individual variability,personalized treatment is often required.In recent years,with the promotion of therapeutic drug monitoring technology,individualized treatment models based on tacrolimus drug concentration have developed rapidly.This article reviews the research progress of individualized dosing models for tacrolimus in children both domestically and internationally over the past decade.It includes dose simulation methods based on population pharmacokinetics,physiologically based pharmacokinetics,machine learning,and multiple linear regression.The characteristics of each model and its application in pediatric individualized dosing are analyzed and summarized.Additionally,the current development status of decision support systems for individualized tacrolimus dosing is introduced.

ObjectiveTo investigate the current status of health literacy among type 2 diabetes mellitus patients in Shanghai communities, to analyze its correlation with glycemic and lipid metabolic indicators and quality of life (QoL), and to provide an evidence for the development of effective intervention measures. MethodsA follow⁃up survey was conducted among diabetic patients diagnosed at hospitals above the secondary level from March to June, 2023, who were part of a diabetes cohort study jointly established by Songnan Community in Baoshan District and the Shanghai Institute of Endocrinology. Patients were assessed using a simplified evaluation form for diabetes-related health literacy and a QoL scale, and metabolic indicators such as blood glucose and blood lipids were measured. Pearson correlation coefficients were employed to assess the relationship between health literacy levels and metabolic indicators as well as QoL. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for the associations between patients’ health literacy levels, metabolic status, and QoL. ResultsAmong the 932 diabetic patients surveyed, the health literacy level was low, with an average score of (65.2±13.4) points of which (62.6±13.8) points for males and (67.9±12.5) points for females. The average QoL score was (44.1±9.2) points of which (44.0±9.5) points for males and (44.2±8.9) points for females. The achievement rates of HbA1c, total cholesterol (TC), and triglycerides (TG) were 51.6%, 30.3%, and 64.8%, respectively. The TC achievement rate among male patients (37.6%) was significantly higher than that among females (22.8%). Significant differences in HbA1c achievement rates were observed across age groups, education levels, disease durations, and BMI levels (P<0.05). Similarly, significant differences were found in FPG achievement rates across different age groups, annual household incomes, disease durations, and family histories (P<0.05). No statistically significant differences were noted in TG and HDL-C achievement rates across all variables (P>0.05). However, LDL-C achievement rates were significantly higher in patients without complications compared to those with complications (P<0.05). Health literacy showed a significant negative correlation with psychological dimension, treatment dimension, and QoL scores (r=-0.14, P<0.05). After adjusting for potential confounding factors, a significant association was found between patients’ health literacy levels and QoL, but not with metabolic indicators. ConclusionThere is a significant correlation between health literacy levels and QoL among diabetic patients in community settings. Further exploration is needed to identify factors influencing patients’ QoL and glycemic and lipid metabolic indicators.

Background At present, the practice of pulmonary rehabilitation for pneumoconiosis in China is in a primary stage. The basis for formulating an individualized comprehensive pulmonary rehabilitation plan is still insufficient, which is one of the factors limiting the development of community-level rehabilitation work. Objective To formulate an exercise prescription based on maximum heart rate measured by cardiopulmonary exercise test (CPET), conduct an individualized comprehensive pulmonary rehabilitation program with the exercise prescription for patients with stable pneumoconiosis, and evaluate its role in improving exercise endurance and quality of life, thus provide a basis for the application and promotion of pulmonary rehabilitation. Methods A total of 68 patients were recruited from the Occupational Disease Prevention Hospital of Jinneng Holding Coal Industry Group Co., Ltd. from April to August 2022 , and were divided into an intervention group and a control group by random number table method, with 34 cases in each group. All the pneumoconiosis patients participated in a baseline test. The control group was given routine drug treatment, while the intervention group received multidisciplinary comprehensive pulmonary rehabilitation treatment on the basis of routine drug treatment, including health education, breathing training, exercise training, nutrition guidance, psychological intervention, and sleep management, whose exercise intensity was determined according to the maximum heart rate provided by CPET. The rehabilitation training lasted for 24 weeks. Patients were evaluated at registration and the end of study respectively. CPET was used to measure peak oxygen uptake per kilogram (pVO₂/kg), anaerobic threshold (AT), carbon dioxide equivalent of ventilation (EqCO₂), maximum metabolic equivalent (METs), and maximum work (W_max). The modified British Medical Research Council Dyspnea Questionnaire (mMRC), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Pittsburgh Sleep Quality Index (PSQI), Chronic Obstructive Pulmonary Disease Assessment Test (CAT), and Short Form of Health Survey (SF-36) were used to evaluate the potential effect of the comprehensive pulmonary rehabilitation program. Results Among the included 68 patients, 63 patients were having complete data, then 31 cases were assigned in the control group and 32 cases in the interventional group. Before the intervention, there was no significant difference in pVO₂/kg, AT, EqCO₂, METs, or W_max between the two groups (P>0.05). At the end of the trail, the indicators like pVO₂/kg [(19.81±2.38) mL·(min·kg)⁻¹], AT [(14.48±2.33) mL·(min·kg)⁻¹], METs (5.64±0.69), and W_max [(85.25±14) W] of patients in the intervention group were all higher than those [(13.90±2.37) mL·(min·kg)⁻¹, (11.70±1.94) mL·(min kg)⁻¹, (3.97±0.70), and (61.77±14.72) W, respectively] in the control group (P<0.001); there was no significant difference in EqCO₂ between the two groups (P=0.083). Before the trial, there was no significant difference in mMRC, SAS, SDS, PSQI, or CAT scores between the two groups (P>0.05). At the end of the trail, the mMRC score (1.16±0.57), SAS score (27.93±2.12), SDS score (26.48±1.44), PSQI score (1.08±0.88), and CAT score (4.34±3.28) of patients in the intervention group were lower than those [(2.03±0.83), (35.87±6.91), (34.23±6.65), (5.37±3.03), and (13.87±7.53), respectively] in the control group (P<0.001). The SF-36 scores of bodily pain (94.13±10.72), general health (87.50±5.68), vitality (95.31±5.53), mental health (99.88±0.71), and health changes (74.22±4.42) in the intervention group were higher than those [(71.87±32.72), (65.81±15.55), (74.52±16.45), (86.97±16.56), and (29.84±13.50), respectively] in the control group (P<0.001), and no significant difference was found in social functioning and role emotional scores (P>0.05). Conclusion Comprehensive pulmonary rehabilitation can increase the oxygen intake and exercise endurance of pneumoconiosis patients, ameliorate dyspnea symptoms, elevate psychological state and sleep quality, and improve the quality of life.

Background It is a research hotspot to study the changes of metabolites and metabolic pathways in the process of coal worker's pneumoconiosis (CWP) by metabonomics and to explore its pathogenesis. Objective To study the change of metabolites in bronchoalveolar lavage fluid (BALF) of patients with CWP and explore the metabolic regulation mechanism of the disease. Methods Patients with CWP who met the national diagnostic criteria according to Diagnosis of occupational pneumoconiosis (GBZ 70-2015) and underwent massive whole lung lavage were selected as the case group, and patients with tracheostenosis who underwent bronchoscopy were selected as the control group. BALF samples were collected from the cases and the controls. After filtering out large particles and mucus, the supernatant was stored in a −80 ℃ refrigerator. The samples were detected and analyzed by liquid chromatography-mass spectrometry after adding extraction solution, cold bath ultrasonication, and high-speed centrifugation, and the metabolic profiles and related data of CWP patients were obtained. The differential metabolites related to the occurrence and development of CWP were screened by multiple statistical analysis; furthermore, we searched the Kyoto Encyclopedia of Genes and Genomes (KEGG) database for potential metabolic pathways involved in the progression. Results There was no significant difference in the general conditions of the subjects, such as weight, height, age, and length of service among the stage I group, the stage II group, the stage III group, and the control group (P˃0.05). When comparing the CWP stage I group with the control group, 48 differential metabolites were screened out, among which 14 were up-regulated and 34 were down-regulated. A total of 66 differential metabolites were screened out between the patients with CWP stage II and the controls, 14 up-regulated and 52 down-regulated differential metabolites. Compared with the control group, 63 differential metabolites were screened out in the patients with CWP stage III, including 11 up-regulated and 52 down-regulated differential metabolites. There were 36 differential metabolites that may be related to the occurrence of CWP, among which 11 differential metabolites were up-regulated, and 25 were down-regulated. Four significant differential metabolic pathways were identified through KEGG database query: linoleic acid metabolic pathway, alanine metabolic pathway, sphingolipid metabolic pathway, and glycerophospholipid metabolic pathway. Conclusion The metabolomic study of BALF show that there are 36 different metabolites in the occurrence and development of CWP, mainly associating with linoleic acid metabolism, alanine metabolism, sphingolipid metabolism, and glycerophospholipid metabolism pathways.

Background Pneumoconiosis is a widespread occupational disease in China at present. As a type of lung diseases, its pathological damage is mainly irreversible fibrotic changes in the lungs. Several studies have shown that the occurrence and development of lung diseases such as coal workers' pneumoconiosis are closely related to intestinal flora. Objective To observe intestinal flora of coal workers' pneumoconiosis patients based on the results of 16SrDNA high-throughput sequencing and evaluate the changes of intestinal flora after treatment with tetrandrine tablets. Methods A total of 80 patients with coal workers' pneumoconiosis attending the outpatient clinic of the Department of Occupational Diseases of the Emergency General Hospital from April to July 2022 were enrolled. All patients were treated with tetrandrine tablets for 4 weeks, with group A before the treatment of tetrandrine tablets and group B after the treatment. In the same period, 24 healthy controls (group C) were set up. Stool samples were collected before and after the treatment. Using 16SrDNA high-throughput sequencing, gene V3-V4 sequencing technology, and bioinformatic analysis platform, we evaluated the intestinal flora after treatment by groups. Results The dominant flora at the phylum level and genus level were the same across three groups. The relative abundances of phylum Bacteroidetes, Bifidobacterium, Bacteroides, and Facealibacterium in groups B and C were higher than those in group A, and the relative abundances of phy-lum Actinobacteria, genus Blautia, and genus Romboutsia in groups B and C were lower than those in group A (P＜0.05). The relative abundances of genus Clostridium, genus Megamonas, and genus Lactobacillus in group C was lower than that in groups A and B (P＜0.05). The alpha diversity analysis showed that the Chao1 index was higher in group A than in group C (P＜0.01). Compared with group A, the Shannon index was higher in group B, and the increases of Simpson index were all statistically significant in stage I patients (P＜0.05), but the differences in Chao1 index were not statistically significant (P＞0.05). The differences in the values of Chao1 index, Shannon index, and Simpson index in stage Ⅱ and stage III patients were not statistically significant (P＞0.05). The beta diversity analysis showed that the difference in flora structure between group A and group C was statistically significant (P＜0.05); the differences in flora structure before and after treatment in the same stage patients were statistically significant (P＜0.05). The partial least squares discriminant analysis (PLS-DA) showed that there were significant differences between group A and group C, and between group A and group B. The LEfSe analysis showed that the significant markers contributing to the differences were basically the same in stage I, stage Ⅱ, and stage Ⅲ after treatment, which were mainly phylum Bacteroidetes and its subordinate groups, class Negativicutes, or-der Selenomonas, and genus Facealibacterium. Conclusion There are differences in the distribution of flora between coal workers' pneumoconiosis patients and healthy individuals, and the structure and relative abundance of intestinal flora are changed and the number of beneficial flora is increased after treatment with tetrandrine tablets.

Background Multi-slice spiral computerized tomography (MSCT) can be used as an auxiliary diagnosis of chest radiography in diagnosis of pneumoconiosis, but there are few studies on the correlations between interstitial images and stage classification of coal workers' pneumoconiosis in the existing literature. Objective To present MSCT imaging manifestations and distribution characteristics of coal workers' pneumoconiosis and complications, evaluate correlations between coal workers' pneumoconiosis stages and pulmonary interstitial lesions, and provide a reliable imaging diagnosis basis for pneumoconiosis interstitial lesions. Methods From June 2022 to June 2023, a total of 1002 patients with coal workers' pneumoconiosis confirmed by the pneumoconiosis diagnostic and identification group in the Department of Occupational Diseases of the Emergency General Hospital were enrolled. MSCT was used to observe the abnormal imaging manifestations of the lungs of coal workers' pneumoconiosis patients and the diseases of pulmonary fibrosis related to their own diseases (thickening of the interlobular septum, bronchial perivascular interstitial mass thickening, parenchymal banding, subpleural line, intralobular interstitial thickening, honeycomb, and subpleural interstitial thickening), the occurrence of coal workers' pneumoconiosis and complications (old tuberculosis, active tuberculosis, pneumonia, atelectasis, lung cancer, bronchiectasis), and the density, size, and location of pneumoconiosis nodules. Imaging data were analyzed and statistically processed. Results All 1002 patients were male, with an average age of (60.71±6.87) years and an average dust exposure time of (23.01±7.80) years. Among them, there were 470 patients with stage I, 422 patients with stage II, and 110 patients with stage III. There were significant differences in the distribution of thickening of the interlobular septum, bronchial perivascular interstitial mass thickening, parenchymal banding, intralobular interstitial thickening, subpleural interstitial thickening, and honeycomb across different stages (P<0.05). Statistically significant differences in p, q, and r subsets of round nodules were found in patients with pneumoconiosis at different stages (P<0.05). Observed nodule types included solid nodules, pure ground-glass shadow nodules, and partial solid nodules. There were statistically significant differences in pulmonary tuberculosis and bronchiectasis among different stages of coal workers' pneumoconiosis (P<0.05). There were statistically significant differences in interstitial shadows and patches combined with interstitial shadows among different stages of pneumoconiosis complicated with pneumonia (P<0.05). Conclusion MSCT provides images of the progression of coal workers' pneumoconiosis and have a certain relationship with the stages of coal workers' pneumoconiosis, which is conducive to the formulation of reasonable treatment plans in the early clinical stage. Therefore, in the diagnosis and treatment of pneumoconiosis, a great attention should be paid to the imaging technology of chest computerized tomography, especially the use of MSCT examination.