BACKGROUND:Osteosarcoma has a complex pathogenesis and a poor prognosis.While advancements in medical technology have led to some improvements in the 5-year survival rate,substantial progress in its treatment has not yet been achieved. OBJECTIVE:To screen key molecular markers in osteosarcoma,analyze their relationship with osteosarcoma treatment drugs,and explore the potential disease mechanisms of osteosarcoma at the molecular level. METHODS:GSE99671 and GSE284259(miRNA)datasets were obtained from the Gene Expression Omnibus database.Differential gene expression analysis and Weighted Gene Co-expression Network Analysis(WGCNA)on GSE99671 were performed.Functional enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes separately for the differentially expressed genes and the module genes with the highest positive correlation to the disease.The intersection of these module genes and differentially expressed genes was taken as key genes.A Protein-Protein Interaction network was constructed,and correlation analysis on the key genes was performed using CytoScape software,and hub genes were identified.Hub genes were externally validated using the GSE28425 dataset and text validation was conducted.The drug sensitivity of hub genes was analyzed using the CellMiner database,with a threshold of absolute value of correlation coefficient|R|>0.3 and P<0.05. RESULTS AND CONCLUSION:(1)Differential gene expression analysis identified 529 differentially expressed genes,comprising 177 upregulated and 352 downregulated genes.WGCNA analysis yielded a total of 592 genes with the highest correlation to osteosarcoma.(2)Gene Ontology enrichment results indicated that the development of osteosarcoma may be associated with extracellular matrix,bone cell differentiation and development,human immune regulation,and collagen synthesis and degradation.Kyoto Encyclopedia of Genes and Genomes enrichment results showed the involvement of pathways such as PI3K-Akt signaling pathway,focal adhesion signaling pathway,and immune response in the onset of osteosarcoma.(3)The intersection analysis revealed a total of 59 key genes.Through Protein-Protein Interaction network analysis,8 hub genes were selected,which were LUM,PLOD1,PLOD2,MMP14,COL11A1,THBS2,LEPRE1,and TGFB1,all of which were upregulated.(4)External validation revealed significantly downregulated miRNAs that regulate the hub genes,with hsa-miR-144-3p and hsa-miR-150-5p showing the most significant downregulation.Text validation results demonstrated that the expression of hub genes was consistent with previous research.(5)Drug sensitivity analysis indicated a negative correlation between the activity of methotrexate,6-mercaptopurine,and pazopanib with the mRNA expression of PLOD1,PLOD2,and MMP14.Moreover,zoledronic acid and lapatinib showed a positive correlation with the mRNA expression of PLOD1,LUM,MMP14,PLOD2,and TGFB1.This suggests that zoledronic acid and lapatinib may be potential therapeutic drugs for osteosarcoma,but further validation is required through additional basic experiments and clinical studies.

[摘 要] 目的：基于加权基因共表达网络分析（WGCNA）探讨贝沙罗汀治疗双打击淋巴瘤（DHL）的分子机制，为DHL治疗提供潜在靶点和实验依据。方法：从基因表达综合数据库（GEO）下载GSE44164和GSE43677表达谱数据集，筛选出差异表达基因（DEG）。采用WGCNA识别与DHL相关的基因模块，构建蛋白质相互作用（PPI）网络以筛选关键基因。通过药物预测平台EpiMed进行关联分析以确定DHL的潜在靶向治疗药物。利用CCK-8法和WB法检测贝沙罗汀对DHL细胞增殖及关键蛋白表达的影响，通过流式细胞术评估贝沙罗汀诱导细胞凋亡的效果。结果：WGCNA识别出与DHL高度相关的碧绿色模块，在PPI网络中筛选出10个枢纽基因，包括COL1A2、COL3A1、MMP2、COL5A2、DCN、BGN、FN1、MMP9、FBN1和LUM。药物关联分析确定贝沙罗汀为潜在治疗药物。体外实验显示，贝沙罗汀显著抑制U2932细胞活力（P < 0.05）、促进细胞凋亡（P < 0.001）、下调细胞中c-Myc和COL1A2的表达（均P < 0.05）。结论：贝沙罗汀可能通过抑制c-Myc信号通路及调控细胞外基质相关基因发挥抗DHL作用，其体内疗效及联合治疗潜力需进一步验证。

The diagnostic frequency of multiple pulmonary tumor nodules has increased significantly in clinical practice. Among patients with multiple pulmonary nodules, distinguishing between separate primary lung carcinomas and intrapulmonary metastases is critical for accurate tumor staging, therapeutic decision-making, and prognostic evaluation. The consensus document "Differentiating separate primary lung adenocarcinomas from intrapulmonary metastases with emphasis on pathological and molecular considerations: Recommendations from the International Association for the Study of Lung Cancer Pathology Committee" highlights the pivotal role of integrated pathological and molecular analyses in diagnosing and differentiating primary lung adenocarcinomas from intrapulmonary metastatic lesions. It further proposes a combined four-step histologic and molecular classification algorithm for addressing multiple pulmonary tumor nodules of adenocarcinoma histology, providing clinicians with enhanced diagnostic tools to refine staging accuracy, guide therapeutic strategies, and improve prognostic predictions for lung adenocarcinoma. Building on current advancements in global research, this article offers a comprehensive interpretation of the consensus recommendations.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

Objective To evaluate the application efficacy of low-dose test method combined with variable helical pitch(VHP)technology in computed tomography angiography(CTA)of lower extremity arteries.Methods Eighty patients with CTA imaging of bilateral lower extremity arteries were selected and divided into group A and group B on average.VHP technology was used in group A,and conventional fixed pitch scanning was used in group B.The objective and subjective image quality of the two groups were compared,and the radiation dose and contrast agent dosage of the two groups were recorded and compared.Results The subjective image quality evaluation of group A was significantly better than that of group B,and the difference was statistically significant(Kappa test,P<0.05).In the objective image quality evaluation,the CT value and signal-to-noise ratio(SNR)value of the common iliac artery,popliteal artery and anterior tibial artery in group A were higher than those in group B at the same level,and the differences were statistically significant(P<0.05);The effective dose(ED)value in group A was(6.74±1.20)mSv,and that in group B was(7.93±1.78)mSv(P<0.05).The dosage of contrast agent in group A was significantly lower than that in group B[(73.97±12.15)mL in group A,(82.50±2.61)mL in group B](P<0.05).Conclusion Low-dose test method combined with VHP technology not only can reduce the radiation dose and contrast agent dosage,but also can effectively improve the success rate and image quality of lower extremity arteries examination,which is worthy of clinical application.

Objective To evaluate five types of DIC scoring systems based on sepsis patients,to explore the values of different DIC scoring systems in the occurrence and prognosis of DIC in sepsis patients,and to compare the applicability of different DIC scoring systems for sepsis complicated with DIC.Methods Laboratory indexes and clinical data from sepsis patients who had been hospitalized in Gansu Provincial People's Hospital from December 1,2019 to December 31,2021 were retrospectively analyzed within 24 hours.Five types of DIC scoring systems were used to score,and the difference of diagnostic rate and discharge outcome in sepsis patients with different severity was compared.The ROC curves of five DIC scoring systems were established to evaluate the accu-racy of DIC in sepsis patients.Results The fatality rate of sepsis increased with the severity of sepsis(P<0.05).There were statistically significant differences in discharge outcomes between DIC and non-DIC in the five scoring systems(P<0.05).JMHW,CDSS and part of ISTH were detected in JAAM cases,while ISTH was detected in non-dominant ISTH cases.ISTH,JAAM,JMHW,CDSS,and non-dominant ISTH5 scoring systems were used to diagnose DIC,and absence of full health restoration and death were 3.0,3.8,4.2,3.9,and 3.0 times higher than non-DIC cases,respectively.Conclusion JAAM scoring system has higher diagnostic rate and sensitivity for adult sepsis.CDSS and JMHW scoring systems are more accurate in predicting the prognosis of sepsis patients.

OBJECTIVE To establish a performance index evaluation system for pharmacists in inpatient pharmacy to encourage and guide pharmacists to achieve self-professional growth and reshape their own values. METHODS According to the evaluation criteria for the construction of provincial-level clinical specialties in Jiangsu province, the key success factors(KSF) method was used to set the key indicators for the discipline construction of the department, and the key process indicator(KPI) method was used for the daily work of the department. Based on the combination of KSF and KPI, an inpatient pharmacy performance management system was established, employee and clinical satisfaction, ward complaints, error occurrence rate, dispensing efficiency, and scientific research output were taken as indicators to evaluate the effect after the implementation of the performance management system. RESULTS Before and after the construction and implementation of the "KSF + KPI" performance system, the average employee satisfaction had increased from 57.75% to 77.81%(P<0.05), the number of complaints in the ward had decreased from (26.33±6.75) per month to (7.17±3.61) per month, and the number of errors had decreased from (30.33±5.50) per month to (12.58±2.75) per month, the differences were statistically significant(P<0.05). Overall clinical satisfaction reached 81.13%; the PIVAS blending efficiency had been improved to a certain extent, with an average increase of 17%. Innovation related indicators such as article writing, recruitment, project application, and employee research participation had significantly improved after implementation of the indicator performance system. CONCLUSION The inpatient pharmacy performance management system establishes based on "KSF and KPI" provides a good performance evaluation scheme for the transformation and development of the dispensing department of the pharmaceutical department. It has made positive exploration in the aspects of self-motivation and professional development of hospital pharmacists, high-efficiency operation, improvement of clinical service level and development of pharmaceutical discipline, and has achieved good results.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative 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:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective:To establish a predictive model for the progression of acute kidney injury (AKI) to stage 3 AKI (renal failure) in the intensive care unit (ICU), so as to assist physicians to make early and timely decisions on whether to intervene in advance.Methods:A retrospective analysis was conducted. Thirty-eight patients with AKI admitted to the intensive care medicine of the Third People's Hospital of Henan Province from January 2018 to May 2023 were enrolled. Patient data including acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) upon admission, serum creatinine (SCr), blood urea nitrogen (BUN), daily urine output during hospitalization, and the timing of continuous renal replacement therapy (CRRT) intervention were recorded. Based on clinically collected pathological data, standardized creatinine value ratio mean polynomial fitting models were established as the first criterion for judging the progression to stage 3 AKI after data cleansing, screening, and normalization. Additionally, standardized creatinine value ratio index fitting models were established as the second criterion for predicting progression to stage 3 AKI.Results:A total of 38 AKI patients were included, including 25 males and 13 females. The average age was (58.45±12.94) years old. The APACHEⅡ score was 24.13±4.17 at admission. The intervention node was (4.42±0.95) days. Using a dual regression model approach, statistical modeling was performed with a relatively small sample size of statistical data samples, yielding a scatter index non-linear regression model for standardized creatinine value ratio data relative to day " n", with y = 1.246?2 x1.164?9 and an R2 of 0.860?1, indicating reasonable statistical fitting. Additionally, a quadratic non-linear regression model was obtained for the mean standardized creatinine value ratio relative to day " n", with y = -0.260?6 x2+3.010?7 x-1.612 and an R2 of 0.998?9, indicating an excellent statistical fit. For example, using a baseline SCr value of 66 μmol/L for a healthy individual, the dual regression model predicted that the patient would progress to stage 3 AKI within 3-5 days. This prediction was consistent when applied to other early intervention renal injury patients. Conclusion:The established model effectively predicts the time interval of the progression of AKI to stage 3 AKI (renal failure), which assist intensive care physicians to intervene AKI as early as possible to prevent disease progression.