[Objective] To validate and optimize the platelet transfusion refractoriness (PTR) prediction model for patients with hematological disorders established by our center. [Methods] The data of patients with hematological diseases who received platelet transfusions from December 2021 to December 2022 were used as the training set, and data from January 2023 to December 2023 as the validation set. The validation set data was used to validate the predictive model constructed on the training set. Relevant risk factors for PTR were collected through literature review and preliminary studies。 The patients were divided into effective and ineffective groups according to the corrected count increment (CCI) of platelet counts. Predictive factors were screened using univariate and multivariate logistic regression. The calibration of the model were assessed via calibration curves, while discrimination, accuracy, sensitivity, and specificity were evaluated using receiver operating characteristic (ROC) curves Clinical utility was further analyzed with decision curve analysis (DCA). [Results] The Hosmer-Lemeshow (H-L) goodness-of-fit test for the validation set yielded S: P=0.000, indicating that the original model needs optimization. Baseline comparisons and logistic regression identified the number of red blood cell units (RBCU) and platelet units (PLT-U) transfused as key predictors for the optimized model. The H-L goodness-of-fit test S: P values for the training and validation sets were 0.930 and 0.056, respectively; the ROC areas were 0.793 5 and 0.809 4, specificities 90.95% and 84.21%, sensitivities 59.26% and 70.04%, and accuracies 78.14% and 74.10%, respectively. DCA demonstrated clinical net benefit within a prediction probability threshold range of 0.2-0.8. [Conclusion] Transfusion volumes of RBC-U and PLT-U were inversely associated with PTR in hematological patients. The resulting PTR prediction model exhibits moderate predictive efficacy and clinical benefit.

Objective: To investigate the environmental contamination of norovirus in nurseries and primary/secondary schools, so as to provide a scientific basis for effective prevention and control measures. Methods: A total of 483 external environmental samples were collected from 34 cluster outbreaks of norovirus gastroenteritis in kindergartens and primary/secondary schools in Linhai City from 2021 to 2024. Pathogen detection was conducted using a rapid nucleic acid extraction kit and realtime fluorescence RT-PCR, and the results were analyzed using the χ2 test or Fishers exact test. Results: Among the collected external environmental samples, the total positive rate of surface contamination was 13.66%. The positive rates in kindergartens and primary/secondary schools were 12.20% and 15.82%, respectively. In kindergartens, the five surfaces with the highest detection rates were desks/chairs (23.33%), toilet stool troughs (20.69%), urinal troughs (12.00%), washbasins/sinks (11.11%), and toilet mops (9.38%). In primary/secondary schools, the top five were toilet stool troughs (38.30%), urinal troughs (23.53%), toilet door handles (13.04%), toilet mops (12.50%), and drinking cups (11.11%). The difference in positive detection rates among different external environments in primary/secondary schools was statistically significant (Fishers exact probability test, P<0.01). The positive detection rate in sanitary toilets was higher than that in classroom environments (χ2=17.38), while the positive detection rate in classroom environments of kindergartens was higher than that in primary/secondary schools (χ2=5.42)(P<0.05). Conclusions Norovirus exhibits a high contamination rate in nurseries and schools, particularly in restroom areas. Strengthening sanitation and disinfection in highrisk environments, and improving hygiene awareness among children and staff, are essential for the effective prevent and control of norovirus.

Background Diseases severely affect the efficiency of workers. Comorbidity refers to the coexistence of two or more chronic diseases or health problems in the same individual. Previous studies have primarily focused on occupational injuries caused by environmental exposures, while the analysis of the epidemiological characteristics of self-reported diseases and occupational injuries among manufacturing workers has been insufficient. Objective To analyze the distribution of self-reported diseases and occupational injuries among manufacturing workers, the strength of correlation between different diseases, and common disease combinations, and to preliminarily explore the relationship between self-reported diseases and occupational injuries. Methods A cross-sectional survey was conducted to investigate the occupational injuries of 2382 workers in 2 manufacturing enterprises over the past year, and 2355 questionnaires were valid after cleaning. The questionnaire included three parts: basic information, occupational injury occurrence, and disease prevalence. The self-reported diseases diagnosed by physicians included musculoskeletal diseases, cardiovascular diseases, respiratory diseases, mental health problems, neurological and sensory organ diseases, digestive organ diseases, reproductive and urinary organ diseases, skin diseases, tumors, endocrine and metabolic system diseases, blood diseases and birth defects, a total of 11 types. Log-binomial model was used to calculate the prevalence ratio (PR) value of the association between different diseases, and UpSet diagram was used to present the disease combination pattern. Results In total, 40.2% (946/2355) of the study participants reported at least one disease, while 8.6% (203/2355), 5.2% (122/2355), and 5.9% (140/2355) reported having two, three, and four or more diseases, respectively. A higher prevalence was observed for musculoskeletal diseases, neurological and sensory organ diseases, digestive organ diseases, and skin diseases, which accounted for 18.0% (423/2355), 13.8% (324/2355), 9.3% (218/2355), and 9.1% (214/2355), respectively. Workers with musculoskeletal disorders, cardiovascular diseases, or neurological and sensory organ diseases reported significantly higher incidence of occupational injuries compared with workers without the corresponding diseases (P<0.001, P=0.041, and P=0.006, respectively). Musculoskeletal diseases were strongly associated with comorbidities of neurological and sensory organ diseases (PR values were 1.86 and 1.98, respectively), and the other patters were musculoskeletal diseases and digestive organ diseases (PR and OR values were 1.57 and 2.35, respectively), and musculoskeletal diseases and cardiovascular diseases (PR and OR values were 1.46 and 2.22, respectively). The largest binomial comorbidity group involved musculoskeletal diseases and neurological and sensory organ diseases, accounting for 5.4% (25/465) of the comorbid workers. Conclusion Among the self-reported diseases of manufacturing workers, musculoskeletal diseases, neurological and sensory organ diseases, digestive organ diseases, and skin diseases are more common. Musculoskeletal diseases and neurological and sensory organ diseases are the most common in all comorbidities. Musculoskeletal diseases, cardiovascular diseases, and neurological and sensory organ diseases are associated with occupational injuries. In the prevention and control of occupational injuries, joint prevention strategies targeting multiple diseases should be strengthened.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

OBJECTIVE To provide medication reference for duloxetine use in clinical settings， particularly for patients with depression in primary medical institutions in Xinjiang that lack therapeutic drug monitoring conditions. METHODS The medical records of 281 depression inpatients taking duloxetine in the First Affiliated Hospital of Xinjiang Medical University from January 2022 to December 2023 were retrospectively collected. They were divided into training set （196 cases） and test set （85 cases） in the ratio of 7∶3. Feature selection was performed by encapsulating random forests （RF） with recursive feature elimination. Four machine learning algorithms， namely support vector machine， RF， extreme gradient boosting （XGBoost） and artificial neural network， were used to construct duloxetine blood concentration prediction model. The prediction performance of the models was evaluated and compared by coefficient of determination （R2）， mean absolute error （MAE） and root mean squared error （RMSE）. The feature of the selected optimal model was explained by Shapley additive explanation method， and the importance ranking of the features and the influence on the prediction results of duloxetine blood concentration were determined. RESULTS A total of 29 characteristic variables were selected， including age， ethnicity， body mass index（BMI）， etc. XGBoost showed the highest R2 （0.808）， and the lowest MAE （7.644） and RMSE （10.808）. The ranking of feature importance for predicting the blood concentration of duloxetine was as follows： BMI＞age＞other 20 feature sets （including liver and kidney function and biochemical indicators）＞daily dosage＞comorbidities＞combination therapy＞ethnicity＞white blood cell count＞hemoglobin＞height. CONCLUSIONS XGBoost model possesses the best prediction performance of duloxetine blood concentration； BMI and age have a greater impact on the prediction of duloxetine blood concentration.

A 43-year-old male patient presented with recurrent edema in different anatomical sites for over 10 years, with facial edema worsening 1 day prior to admission. He had been repeatedly admitted to dermatology, general surgery, and emergency departments of external hospitals due to " acute abdomen" and " laryngeal edema, " resistant to antihistamines and glucocorticoid therapy. Physical examination revealed non-pitting swelling of the right upper eyelid, bilateral cheeks, and lips asymmetrically. On the night of admission, he developed acute laryngeal edema with dyspnea, which was promptly treated, leading to clinical stabilization. Laboratory screening during the attack revealed decreased serum complement C4 levels, along with reduced functional activity and concentration of C1 esterase inhibitor, confirming a diagnosis of type 1 hereditary angioedema. The patient received lanadelumab for prophylaxis and achieved satisfactory clinical outcomes. He remains under long-term follow-up.

Background::Sentinel lymph node (SLN) biopsy is gradually accepted as the standard of care in breast cancer patients with down-staged axillary disease after neoadjuvant chemotherapy (NAC). However, it is still difficult to precisely define pre-NAC clinical node-positive (cN1) and post-NAC clinical node-negative (ycN0). This prospective single-center trial was designed to evaluate the feasibility and accuracy of standard targeted axillary dissection (TAD) after NAC in highly selective pre-NAC cN1 patients (not considering ultrasound-based axillary ycN staging).Methods::This prospective trial included patients with initial pre-NAC cT1–3N1M0 invasive breast cancer but with a rigorous definition of cN1 from the Affiliated Cancer Hospital of Zhengzhou University. When NAC was effective (including complete and partial responses) and preoperative axillary palpation was negative, preoperative ultrasound-based axillary staging was not considered, and all patients underwent TAD followed by axillary lymph node (LN) dissection. The detection rate (DR) and false-negative rate (FNR) of TAD were calculated.Results::A total of 82 patients were included, and 77 of them were eligible for data analysis. The DR for TAD was 94.8% (73/77). There were 26 patients with one abnormal LN at the time of diagnosis based on ultrasound, 45 patients with two, and 2 patients with three. One patient had one TAD LN, four patients had two TAD LNs, and 68 patients had three or more TAD LNs. Preoperative axillary palpation yielded negative results for all 73 patients who successfully underwent TAD. Preoperative ultrasound-based ycN0 and ycN+ conditions were detected for 52 and 21 cases, respectively. The FNR was 7.4% (2/27) for standard TAD (≥3 SLNs), which was lower than that of all successful TAD (≥1 SLN; 10.0%, 3/30).Conclusions::In rigorously defined pre-NAC cN1 breast cancer patients, standard TAD is feasible for those with negative axillary palpation after NAC, and FNR is also less than 10%.Registration::chictr.org.cn, ChiCTR2100049093

Objective To analyze the correlation between serum miR-140-5p,vascular endothelial growth factor(VEGF)levels and atherosclerosis in patients with rheumatoid arthritis.Methods A total of 80 pa-tients with rheumatoid arthritis admitted to the hospital from January 2022 to September 2023 were regarded as the study group.The study group was separated into the combined group(46 cases)and the non combined group(34 cases)according to whether there was the middle layer thickening and atheromatous plaque in ca-rotid artery ultrasound.Another 40 healthy individuals who came to physical examination center in the hospi-tal for physical examination were selected as the control group.Quantitative real-time PCR(RT-qPCR)and enzyme linked immunosorbent assay(ELISA)were applied to detect miR-140-5p and VEGF levels in the ser-um of subjects.Ultrasound was applied to examine the carotid intima-media thickness in the combined group and the non combined group.Pearson and Spearman were applied to analyze the correlation between clinical data of patients with rheumatoid arthritis,and Logistic regression model was applied to analyze the factors in-fluencing atherosclerosis in rheumatoid arthritis patients.Results There were differences in rheumatoid fac-tor,erythrocyte sedimentation rate(ESR),carotid intima-media thickness,fasting blood glucose(FPG),fast-ing insulin(FINS),insulin resistance index(HOMA-IR),hypersensitive C-reactive protein(hs-CRP),miR-140-5p,and VEGF among the three groups(P＜0.05).The rheumatoid factor,ESR,carotid intima-media thickness,FPG,hs-CRP,and VEGF in the non combined group and combined group were higher than those in the control group,while FINS,HOMA-IR,and miR-140-5p were lower than those in the control group,and the differences were statistically significant(P＜0.05).The rheumatoid factor,carotid intima-media thick-ness,FPG,hs-CRP,VEGF in the combined group were higher than those in the non combined group,and the differences were statistically significant(P＜0.05),while FINS and miR-140-5p were lower than those in the non combined group,and the differences were statistically significant(P＜0.05).The rheumatoid factor,ca-rotid intima-media thickness and hs-CRP in patients with rheumatoid arthritis were negatively correlated with miR-140-5p(P＜0.05)and were positively correlated with VEGF(P＜0.05),and miR-140-5p was negatively correlated with VEGF(P＜0.05).Rheumatoid factor,carotid intima-media thickness,hs-CRP,VEGF were risk factors for atherosclerosis in patients with rheumatoid arthritis,and miR-140-5p was a protective factor(P＜0.05).Conclusion Serum miR-140-5p and VEGF in patients with rheumatoid arthritis are associated with atherosclerosis,miR-140-5p is a protective factor for atherosclerosis,and VEGF is a risk factor.

Objective:To investigate the effects of selinexor,a inhibitor of nuclear export protein 1(XPO1)on the proliferation inhibition and apoptosis of Kasumi-1 cells in acute myeloid leukemia(AML).Methods:MTS method was used to detect the inhibitory effect of different concentrations of selinexor on the proliferation of Kasumi-1 cells at different time points.The apoptosis rate and cell cycle changes after treatment with different concentration of selinexor were detected by flow cytometry.Results:Selinexor inhibited the growth of Kasumi-1 cells at different time points in a concentration-dependent manner(r24 h=0.7592,r48 h=0.9456,and r72 h=0.9425).Selinexor inhibited Kasumi-1 cells growth in a time-dependent manner(r=0.9057 in 2.5 μmol/L group,r=0.9897 in 5 μmol/L group and r=0.9994 in 10 μmol/L group).Selinexor could induce apoptosis of Kasumi-1 cells in a dose-dependent manner(r=0.9732),and the apoptosis of Kasumi-1 cells was more obvious with the increase of drug concentration.The proportion of G0/G1 phase was significantly increased and the proportion of S phase was significantly decreased after the treatment of Kasumi-1 cells by selinexor.With the increase of drug concentration,the proportion of Kasumi-1 cells cycle arrest in G0/G1 phase was increased and the cell synthesis was decreased.Conclusion:Selinexor can promote the death of tumor cells by inhibiting Kasumi-1 cells proliferation,inducing apoptosis and blocking cell cycle.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.