ObjectiveTo explore the mechanisms of action of Ganlu Xiaodu Dan in treating viral pneumonia by combining network pharmacology and molecular docking with in vivo experimental validation. MethodsNetwork pharmacology and molecular docking were used to predict the core components， target genes， and major pathways of Ganlu Xiaodu Dan. Molecular docking was then applied to verify the interactions between the core components and key targets. Sixty male C57BL/6 mice were randomly divided into six groups （n = 10 per group）， including blank， model， dexamethasone， and Ganlu Xiaodu Dan low-， medium-， and high-dose groups. The blank and model groups were gavaged with physiological saline （10 mL·kg^-1） every 12 h. The dexamethasone group received intraperitoneal injections of dexamethasone （5 mg·kg^-1）. The low-， medium-， and high-dose groups of Ganlu Xiaodu Dan were gavaged with solutions at concentrations of 7.2， 14.4， and 21.6 g·kg^-1， respectively， every 12 h. Lung wet/dry weight ratio （W/D） was measured. Hematoxylin-eosin （HE） staining was used to observe pathological changes in lung tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the expression levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-17， and IL-1β in bronchoalveolar lavage fluid （BALF）. Western blot was performed to detect the expression of phosphoinositide 3-kinase （PI3K） and protein kinase B （Akt） in lung tissue for further validation. ResultsTwelve potential active components of Ganlu Xiaodu Dan were identified through network pharmacology. A total of 306 overlapping target genes were obtained between Ganlu Xiaodu Dan and viral pneumonia. PPI network analysis identified the top 20 key targets， and GO and KEGG enrichment analyses revealed the top 20 signaling pathways. An “active component–target–pathway” network was constructed. Molecular docking demonstrated strong affinity between the core components of Ganlu Xiaodu Dan and key targets related to viral pneumonia. In animal experiments， compared with the blank group， the model group showed severe bronchial epithelial damage， disordered alveolar structure， massive inflammatory cell infiltration， widened alveolar septa， and obvious interstitial edema. W/D， levels of IL-1β， TNF-α， and IL-17 in BALF， and protein expression of p-PI3K/PI3K and p-Akt/Akt in lung tissue were all significantly increased （P<0.05）. Compared with the model group， lung injury in the Ganlu Xiaodu Dan groups and the dexamethasone group was alleviated. W/D and TNF-α levels were significantly decreased （P<0.05）. IL-1β and IL-17 levels were significantly reduced in the medium- and high-dose groups and the dexamethasone group， and the protein expression levels of p-PI3K/PI3K and p-Akt/Akt in lung tissue were significantly decreased （P<0.05）. ConclusionGanlu Xiaodu Dan can alleviate lung injury in viral pneumonia by suppressing the inflammatory response， and its mechanism may be related to the inhibition of PI3K/Akt pathway activation.

ObjectiveTo explore the mechanisms of action of Ganlu Xiaodu Dan in treating viral pneumonia by combining network pharmacology and molecular docking with in vivo experimental validation. MethodsNetwork pharmacology and molecular docking were used to predict the core components， target genes， and major pathways of Ganlu Xiaodu Dan. Molecular docking was then applied to verify the interactions between the core components and key targets. Sixty male C57BL/6 mice were randomly divided into six groups （n = 10 per group）， including blank， model， dexamethasone， and Ganlu Xiaodu Dan low-， medium-， and high-dose groups. The blank and model groups were gavaged with physiological saline （10 mL·kg^-1） every 12 h. The dexamethasone group received intraperitoneal injections of dexamethasone （5 mg·kg^-1）. The low-， medium-， and high-dose groups of Ganlu Xiaodu Dan were gavaged with solutions at concentrations of 7.2， 14.4， and 21.6 g·kg^-1， respectively， every 12 h. Lung wet/dry weight ratio （W/D） was measured. Hematoxylin-eosin （HE） staining was used to observe pathological changes in lung tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the expression levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-17， and IL-1β in bronchoalveolar lavage fluid （BALF）. Western blot was performed to detect the expression of phosphoinositide 3-kinase （PI3K） and protein kinase B （Akt） in lung tissue for further validation. ResultsTwelve potential active components of Ganlu Xiaodu Dan were identified through network pharmacology. A total of 306 overlapping target genes were obtained between Ganlu Xiaodu Dan and viral pneumonia. PPI network analysis identified the top 20 key targets， and GO and KEGG enrichment analyses revealed the top 20 signaling pathways. An “active component–target–pathway” network was constructed. Molecular docking demonstrated strong affinity between the core components of Ganlu Xiaodu Dan and key targets related to viral pneumonia. In animal experiments， compared with the blank group， the model group showed severe bronchial epithelial damage， disordered alveolar structure， massive inflammatory cell infiltration， widened alveolar septa， and obvious interstitial edema. W/D， levels of IL-1β， TNF-α， and IL-17 in BALF， and protein expression of p-PI3K/PI3K and p-Akt/Akt in lung tissue were all significantly increased （P<0.05）. Compared with the model group， lung injury in the Ganlu Xiaodu Dan groups and the dexamethasone group was alleviated. W/D and TNF-α levels were significantly decreased （P<0.05）. IL-1β and IL-17 levels were significantly reduced in the medium- and high-dose groups and the dexamethasone group， and the protein expression levels of p-PI3K/PI3K and p-Akt/Akt in lung tissue were significantly decreased （P<0.05）. ConclusionGanlu Xiaodu Dan can alleviate lung injury in viral pneumonia by suppressing the inflammatory response， and its mechanism may be related to the inhibition of PI3K/Akt pathway activation.

Objective:To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01).Results:The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P=0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P<0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients ( P=0.001), while TP53 ( P=0.024) and BCL2 ( P=0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years ( HR=3.439, 95% CI=1.318~9.874), presence of B symptoms ( HR = 2.871, 95% CI=1.133~7.307), and elevated lactate dehydrogenase ( HR=3.528, 95% CI=1.231~10.66) as independent adverse prognostic factors. Conclusion:Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.

Objective To establish an intelligent ICD coding management system to solve the current difficulties in hos-pital ICD coding management,reduce the error rate of information uploading,and improve the accuracy of coding.Methods An ICD coding management system was constructed,with the national clinical version of ICD coding as the main index system.The mapping relationship between the main index coding and the medical insurance version of ICD coding,as well as the hospital ver-sion of ICD coding,was established to achieve real-time maintenance and adjustment.In accordance with the requirements of na-tional public hospital performance evaluation and hospital level assessment,we will establish the ICD coding"label"function and knowledge base for evaluation indicators,embed them into electronic medical record system(EMR),and implement intelligent prompting functions for clinicians to facilitate systematic statistical analysis of data.Results After the establishment of the sys-tem,the error rate of mapping and uploading information such as disease diagnosis and procedures coding decreased significantly(1.2‰ vs 0.3‰,P＜0.05).The accuracy of the main discharge diagnosis and procedures coding has significantly improved(82％vs 91％,P＜0.05;78％vs 88％,P＜0.05).The satisfaction of clinicians and coders increased significantly(65％vs 82％,P＜0.05;79％vs 88％,P＜0.05).Conclusion This system can reduce the error rate of mapping and uploading infor-mation,improve the accuracy and completeness of coding,enhance the management level of ICD coding,and promote the high-quality development of medical care.

Objective To establish an intelligent ICD coding management system to solve the current difficulties in hos-pital ICD coding management,reduce the error rate of information uploading,and improve the accuracy of coding.Methods An ICD coding management system was constructed,with the national clinical version of ICD coding as the main index system.The mapping relationship between the main index coding and the medical insurance version of ICD coding,as well as the hospital ver-sion of ICD coding,was established to achieve real-time maintenance and adjustment.In accordance with the requirements of na-tional public hospital performance evaluation and hospital level assessment,we will establish the ICD coding"label"function and knowledge base for evaluation indicators,embed them into electronic medical record system(EMR),and implement intelligent prompting functions for clinicians to facilitate systematic statistical analysis of data.Results After the establishment of the sys-tem,the error rate of mapping and uploading information such as disease diagnosis and procedures coding decreased significantly(1.2‰ vs 0.3‰,P＜0.05).The accuracy of the main discharge diagnosis and procedures coding has significantly improved(82％vs 91％,P＜0.05;78％vs 88％,P＜0.05).The satisfaction of clinicians and coders increased significantly(65％vs 82％,P＜0.05;79％vs 88％,P＜0.05).Conclusion This system can reduce the error rate of mapping and uploading infor-mation,improve the accuracy and completeness of coding,enhance the management level of ICD coding,and promote the high-quality development of medical care.

BACKGROUND:Studies have confirmed that up-regulation of microRNA-140 expression can partially inhibit osteoarthritis-like changes in knee cartilage tissues and cells and delay the progression of osteoarthritis,suggesting that microRNA-140 is involved in the pathogenesis of osteoarthritis.OBJECTIVE:To further analyze the mechanism of microRNA-140 involvement in osteoarthritis by loading exosomes overexpressing microRNA-140 with sodium alginate/collagen hydrogel.METHODS:Lentivirus was used to infect rat bone marrow mesenchymal stem cells to overexpress microRNA-140,then exosomes were isolated and exosomes overexpressing microRNA-140 were obtained.Sodium alginate/collagen hydrogels loaded with exosomes were prepared.Thirty-two SD rats were randomly divided into four groups,with 8 rats in each group.Normal control group did not receive any treatment.The osteoarthritis model was established by injecting sodium iodoacetate into the knee cavity in the osteoarthritis group,the non-transfected exosome group and the transfected exosome group.Two weeks later,PBS was injected into the knee cavity in the osteoarthritis group.Sodium alginate/collagen hydrogel carrying non-overexpressing microRNA-140 and overexpressing microRNA-140 exosomes were injected into the knee cavity of the non-transfected exosome group and transfected exosome group.At 6 weeks after modeling,the threshold of mechanical foot withdrawal response,the concentration of inflammatory factors in synovial fluid,the expression of chondrogen-related genes,the histological changes of knee cartilage and the expression of pyroptosis related proteins were detected in rats.RESULTS AND CONCLUSION:(1)Compared with normal control group,the threshold value of mechanical stimulation foot contraction response,type Ⅱ collagen,SOX9 mRNA expression levels,and Type Ⅱ collagen immunofluorescence intensity were decreased in the osteoarthritis group(P<0.05),and proinflammatory cytokine levels were increased in synovial fluid(P<0.05).The mRNA expressions of matrix metalloproteinase 13 and a disintegrin and metalloproteinase with thrombospondin motifs-5(ADAMTS-5)were increased(P<0.05),and the protein expression levels of NLRP3,ASC,GSDMD p30,caspase-1 p20,interleukin-1β,and interleukin-18 were increased(P<0.05).Immunofluorescence intensity of GSDMD and cleaved caspase-1 was increased(P<0.05),and cartilage tissue was severely damaged.(2)Compared with osteoarthritis group,the threshold value of mechanical stimulation foot contraction response,type Ⅱ collagen,SOX9 mRNA expression levels,and type Ⅱ collagen immunofluorescence intensity in the non-transfected and transfected exosome groups were increased(P<0.05);proinflammatory cytokine levels were decreased in synovial fluid(P<0.05).The mRNA expression of matrix metalloproteinase 13 was decreased(P<0.05),and the protein expression levels of NLRP3,ASC,GSDMD p30,caspase-1 p20,interleukin-1β,and interleukin-18 were decreased(P<0.05).The immunofluorescence intensity of GSDMD and cleaved caspase-1 decreased(P<0.05),and the cartilage tissue damage was reduced(P<0.05),and the effect was stronger in the transfected exosome group.(3)These results conclude that microRNA-140 can reduce the pain response of rats with osteoarthritis by inhibiting inflammation,maintaining cartilage homeostasis,and inhibiting cartilaginous pyroptosis,thereby reducing cartilage damage and playing a therapeutic role in osteoarthritis.

To address the limitations of convolutional neural networks in global context modeling and the complexity of secondary computation in Transformer's self attention mechanism,an improved multi-direction-MambaUNet(MD-MambaUNet)based on MambaUNet is proposed.This network integrates with multi directional selective scanning module to extract spatial features from multiple directions of CT images,significantly improving the global context modeling capability.By introducing partial convolution and constructing a lightweight hybrid convolution module,the model's parameter count is significantly reduced,enabling the processing of large-scale medical image data at lower computational costs while maintaining high-level performance.Experiments are conducted on the LiTS2017 and 3DIRCADB public datasets.Compared with MambaUNet on the LiTS2017 dataset,MD-MambaUNet improves the Dice similarity coefficient for liver and tumor segmentation by 3.32%and 4.77%,reaching 95.36%and 76.93%,and increases intersection over union by 4.18%and 4.92%,reaching 91.43%and 69.74%,respectively.Compared with MambaUNet on the 3DIRCADB dataset,MD-MambaUNet improves the Dice similarity coefficient for liver and tumor segmentation by 2.08%and 2.21%,reaching 93.81%and 64.68%,and increases intersection over union by 0.79%and 3.13%,reaching 87.23%and 57.65%,respectively.Meanwhile,the parameter count is 13.71 M less than MambaUNet,making it possible for the model to be deployed in clinical scenarios.

Objective To explore the pharmacokinetic characteristics of sufentanil in individuals with normal body mass index(BMI),overweight BMI,and different CYP3A4/5 enzyme genotypes.Methods The patients receiving laparoscopic surgery under general anesthesia in the First Affiliated Hospital of Army Medical University from November 2020 to September 2021 were prospectively recruited in this study.Before the operation,the oral swabs were collected from all the patients for genotyping using the human CYP3A4/5 gene kit.Based on the potential impact of combination of their polymorphisms on sufentanil metabolism and the proportion of different genotype combinations of CYP3A4/5 enzymes,the patients were divided into groups I(3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation),II(3A4 heterozygous mutation+3A5 heterozygous mutation),and III(3A4 wild type or 3A4 heterozygous mutation+3A5 wild type).According to their BMI,they were also assigned into a normal body weight group(18.5～24.0 kg/m2)and an overweight group(24～<28 kg/m2),and the differences in drug metabolism parameters were statistically analyze between the 2 groups.After routine general anesthesia induction(sufentanil 0.5 μg/kg),venous blood samples were collected to detect the changes in its concentration using high performance liquid chromatography-mass spectrometry(HPLC-MS).The pharmacokinetic data of sufentanil were calculated between the normal BMI group and overweight group in all participants and between the 2 body weight groups among those with different genotype combinations.Results Among the 90 participants completing the blood drug concentration test,8 patients had their blood samples contaminated(including 1 case with an anesthesia duration of<2 h),and 3 were excluded due to low weight or overweight.Eventually,79 participants were included in the pharmacokinetic analysis on the normal body weight group and the overweight group.Compared with the normal body weight group,the central compartment volume of distribution in the overweight group was significantly reduced(P<0.05),while no obvious differences were observed between the 2 groups in terms of peripheral compartment volume of distribution,total clearance rate,peripheral compartment clearance rate,distribution half-life,clearance half-life,and area under the blood concentration-time curve.In group Ⅰ(n=26),the overweight patients(n=13)had significantly reduced central compartment volume of distribution,peripheral compartment volume of distribution,and peripheral compartment clearance rate when compared with the normal body weight patients(n=13)(P<0.05),while no differences were observed in other pharmacokinetic parameters.In groups Ⅱ(n=25)and Ⅲ(n=28),the overweight patients and normal body weight patients had no statistical differences in all pharmacokinetic parameters.Conclusion Among the patients with the same genotype combination of CYP3A4/5 mutations,there was no difference in the metabolism of sufentanil between the overweight and normal weight patients.Additionally,in the population of 3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation,the overweight patients have smaller peripheral distribution range of sufentanil,and weakened metabolic process.

Objective The kinetic parameters of Lin's squeezing-pressing adjustment manipulation were collected for the analysis of its mechanical characteristics,thus to establish a standardized operating procedure to guide clinical teaching of this technique.Methods Ten healthy male trainees(aged 20-30 years)from the Tuina Department of Guangdong Provincial of Chinese Medicine were selected as the subjects.A multi-point thin-film pressure testing system was used to collect mechanical parameters during the operation of Lin's squeezing-pressing adjustment manipulation.The mechanical characteristics were analyzed,and then a mathematical model of time-mechanics curve was constructed.Results(1)The kinetic parameters of Lin's squeezing-pressing adjustment manipulation were as follows:preload force averaged(279.45±19.36)N with a duration of(0.98±0.03)s,the valley value of preload force averaged(137.45±3.59)N,the maximum impact force was(495.56±7.33)N,the impact duration averaged(0.15±0.01)s,the impact velocity averaged(3 183.96±94.76)N/s,and the impulse was(57.16±1.82)N/s.(2)The fitting function of impact force showed large absolute values for both ascending and descending slopes,and the ascending slope was significantly greater than the descending slope,indicating that the Lin's manipulation stressed on rapid outburst of the strength and withdrawal of the strength.(3)One-way ANOVA revealed no statistically significant differences in the preload force and its duration and valley value,the maximum impact force,and impact time among different operators(P＞0.05).Conclusion The analysis of kinetic parameters demonstrates that skilled operators maintain relatively stable mechanical parameters when performing Lin's squeezing-pressing adjustment manipulation.This study provides a preliminary digital analysis of the mechanical characteristics of Lin's bone-setting manipulation in addressing"bone misalignment and tendon displacement",which supplies objective evaluation criteria for the technique.

The paper discusses the scientific connotation of"heart and brain co-dominating the mind",including the connotation of"heart and brain co-dominating the mind"in traditional Chinese medicine and the physiological and pathological relationship be-tween heart and brain in modern medicine.Based on the understanding of"heart and brain co-dominating the mind",this paper be-lieves that"restlessness of mind"is the core pathogenesis of insomnia,and regulating mind is the key to the acupuncture and moxibus-tion treatment of insomnia.The autonomic nervous system(ANS)is a bridge connecting the heart and brain,and is closely related to the central anatomy,neurotransmitters and physiological rhythms of sleep.The imbalance of ANS is highly consistent with the patho-genesis of"heart and brain restlessness"in traditional Chinese medicine.The Governor Vessel runs through the brain and the heart,and the"Governor Vessel regulating spirit acupuncture"can communicate the heart and brain,regulate ANS function,and thus im-prove sleep quality.