Objective:To investigate the influence and mechanisms of metformin on the proliferation and apoptosis of human keloid fibroblasts (Fbs).Methods:This study was an experimental research. The keloid tissue was collected from 7 keloid patients (2 males and 5 females, aged 20-65 years, with a disease course of more than 1 year) who underwent keloid excision surgery at the Department of Plastic, Cosmetic and Maxillofacial Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from September 2020 to September 2023. The primary Fbs were isolated and cultured, and cells from passages 3 to 6 were used for experiments. The cells were divided into control group and metformin group, and were cultured in complete medium. The medium for metformin group was supplemented with metformin at a final molarity of 60 mmol/L. The cell counting kit-8 was used to assess the proliferation activity of cells in two groups after 12 and 24 hours of culture, and the proliferation inhibition rate of cells in metformin group after 12 and 24 hours of culture was calculated, with a sample size of 6. The apoptosis detection kit was used to detect the apoptotic distribution of cells in control group after 0 hour (immediately) of culture and in metformin group after 12 and 24 hours of culture, with a sample size of 3. The cell cycle detection kit was used to detect the cycle distribution of cells in two groups after 12 and 24 hours of culture, with a sample size of 3. The eukaryotic mRNA sequencing was performed on suitable number of cells of two groups after 24 hours of culture, and the Kyoto encyclopedia of genes and genomes functional annotation analysis and functional enrichment analysis were performed after screening for differentially expressed genes (DEGs) with significantly differential expression between two groups. Western blotting was conducted to detect the protein expressions of phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt), and phosphorylated mammalian target of rapamycin (p-mTOR) in the PI3K/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway of cells in two groups after 24 hours of culture, with a sample size of 3.Results:After 12 and 24 hours of culture, the proliferation activity of cells in metformin group was significantly lower than that in control group (with t values of 4.70 and 24.02, respectively, P<0.05); the proliferation activity of cells in metformin group after 24 hours of culture was significantly lower than that after 12 hours of culture within the group ( t=4.73, P<0.05). Compared with that after 12 hours of culture within the group, the proliferation inhibition rate of cells in metformin group was significantly increased after 24 hours of culture ( t=5.29, P<0.05). Compared with that in control group after 0 hour of culture, the proportion of early apoptotic cells in metformin group was significantly increased (with t values of 6.62 and 4.58, respectively, P<0.05), and the proportion of early and late apoptotic cells was significantly increased after 12 and 24 hours of culture (with t values of 4.84 and 3.75, respectively, P<0.05). After 24 hours of culture, the proportion of late apoptotic cells in metformin group was significantly higher than that after 12 hours of culture within the group ( t=4.55, P<0.05). After 12 hours of culture, the proportion of S-phase cells in metformin group was significantly lower than that in control group ( t=5.90, P<0.05). After 24 hours of culture, compared with that in control group, the proportion of G0/G1-phase cells in metformin group was significantly increased ( t=5.36, P<0.05), while the proportion of G2/M-phase cells was significantly decreased ( t=17.63, P<0.05). The proportion of S-phase cells in metformin group after 24 hours of culture was significantly higher than that after 12 hours of culture within the group ( t=7.60, P<0.05). After 24 hours of culture, 4 814 DEGs with significantly differential expression were detected in the cells of metformin group compared with control group. The significantly upregulated and downregulated DEGs were mainly involved in biological functions related to signal transduction, cell growth and death, transport and catabolism, the endocrine system, the immune system, and cancer. The pathways that were significantly enriched with DEGs with significantly differential expression included the cell cycle and DNA replication, with the highest number of genes in the PI3K/Akt signaling pathway. After 24 hours of culture, the protein expressions of PI3K, p-Akt, and p-mTOR of cells in metformin group were 0.190±0.017, 0.170±0.017, and 0.247±0.005, respectively, which were significantly lower than 0.440±0.026, 0.300±0.060, and 0.547±0.025 in control group (with t values of 13.69, 3.61, and 20.12, respectively, P values all <0.05). Conclusions:Metformin can significantly inhibit the proliferation of human keloid Fbs through the PI3K/Akt/mTOR signaling pathway and effectively induce its apoptotic process, thereby exerting antifibrotic effects.

ObjectiveBased on ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， the chemical constituents of Qili Qiangxin capsules was identified， and their distribution in vivo was analyzed. MethodsUPLC-Q-Orbitrap-MS was used to detect the sample solution of Qili Qiangxin capsules， as well as the serum， brain， heart， lung， spleen， liver and kidney tissues of mice after oral administration. Using the Thermo Xcalibur 2.2 software， the compound information database was constructed， and the molecular formulas of compounds corresponding to the quasi-molecular ions were fitted. Based on the information of retention time， accurate relative molecular mass and fragments， the compounds and their distribution in vivo were analyzed by comparing with the data of reference substances and literature. ResultsA total of 233 compounds， including 70 terpenoids， 60 flavonoids， 23 organic acids， 17 alkaloids， 20 steroids， 7 coumarins and 36 others， were identified or predicted from Qili Qiangxin capsules， 73 of which were identified matching with standard substances. Tissue distribution results showed that 71， 17， 38， 33， 32， 58 and 43 migrating components were detected in blood， brain， heart， lung， spleen， liver and kidney， respectively. Thirty-seven components were absorbed into the blood and heart， including quinic acid， benzoylaconitine benzoylmesaconine and so on. Fourteen components were absorbed into the blood and six tissues， including calycosin， methylnissolin， formononetin， alisol B， alisol A and so on. ConclusionThis study comprehensively analyzes the chemical components of Qili Qiangxin capsules and their distribution in vivo. Among them， astragaloside Ⅳ， salvianolic acid B， ginsenoside Rb₁， ginsenoside Rb₃， ginsenoside Rd， ginsenoside Rg₃， calycosin-7-glucoside， and sinapine may be the important components for the treatment of heart failure， which can provide useful reference for its quality control and research on pharmacodynamic material basis.

Thoracolumbar trauma, including fractures, dislocations and spinal cord injuries, often result from high-energy injuries such as traffic accidents and falls from heights. It not only causes severe pain and restricted movement for patients, but also leads to neurological damage and even permanent disability. Currently, the diagnosis and treatment of thoracolumbar trauma are faced with many problems, such as possible missed diagnosis and misdiagnosis, lack of individualized and standardized treatment plans, and lack of objective and quantitative metrics for postoperative assessment. Artificial intelligence (AI) technology offers innovative ideas to these problems. Among them, the core AI technology such as machine learning (ML), deep learning (DL), computer vision, and robotics has demonstrated outstanding capabilities in medical image analysis, clinical decision support, etc., which can significantly improve the diagnostic precision, surgical planning efficiency, and postoperative management level of thoracolumbar trauma. At present, application of AI technology in cross-modal data integration, clinical decision support, and long-term efficacy prediction in the field of thoracolumbar trauma remains to be systematically sorted out. To this end, the authors reviewed the research progress of AI technology in the diagnosis, treatment, and postoperative management of thoracolumbar trauma, providing a reference for a wide application of AI technology in the management of thoracolumbar trauma.

Thoracolumbar trauma, including fractures, dislocations and spinal cord injuries, often result from high-energy injuries such as traffic accidents and falls from heights. It not only causes severe pain and restricted movement for patients, but also leads to neurological damage and even permanent disability. Currently, the diagnosis and treatment of thoracolumbar trauma are faced with many problems, such as possible missed diagnosis and misdiagnosis, lack of individualized and standardized treatment plans, and lack of objective and quantitative metrics for postoperative assessment. Artificial intelligence (AI) technology offers innovative ideas to these problems. Among them, the core AI technology such as machine learning (ML), deep learning (DL), computer vision, and robotics has demonstrated outstanding capabilities in medical image analysis, clinical decision support, etc., which can significantly improve the diagnostic precision, surgical planning efficiency, and postoperative management level of thoracolumbar trauma. At present, application of AI technology in cross-modal data integration, clinical decision support, and long-term efficacy prediction in the field of thoracolumbar trauma remains to be systematically sorted out. To this end, the authors reviewed the research progress of AI technology in the diagnosis, treatment, and postoperative management of thoracolumbar trauma, providing a reference for a wide application of AI technology in the management of thoracolumbar trauma.

Objective:To investigate the influence and mechanisms of metformin on the proliferation and apoptosis of human keloid fibroblasts (Fbs).Methods:This study was an experimental research. The keloid tissue was collected from 7 keloid patients (2 males and 5 females, aged 20-65 years, with a disease course of more than 1 year) who underwent keloid excision surgery at the Department of Plastic, Cosmetic and Maxillofacial Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from September 2020 to September 2023. The primary Fbs were isolated and cultured, and cells from passages 3 to 6 were used for experiments. The cells were divided into control group and metformin group, and were cultured in complete medium. The medium for metformin group was supplemented with metformin at a final molarity of 60 mmol/L. The cell counting kit-8 was used to assess the proliferation activity of cells in two groups after 12 and 24 hours of culture, and the proliferation inhibition rate of cells in metformin group after 12 and 24 hours of culture was calculated, with a sample size of 6. The apoptosis detection kit was used to detect the apoptotic distribution of cells in control group after 0 hour (immediately) of culture and in metformin group after 12 and 24 hours of culture, with a sample size of 3. The cell cycle detection kit was used to detect the cycle distribution of cells in two groups after 12 and 24 hours of culture, with a sample size of 3. The eukaryotic mRNA sequencing was performed on suitable number of cells of two groups after 24 hours of culture, and the Kyoto encyclopedia of genes and genomes functional annotation analysis and functional enrichment analysis were performed after screening for differentially expressed genes (DEGs) with significantly differential expression between two groups. Western blotting was conducted to detect the protein expressions of phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt), and phosphorylated mammalian target of rapamycin (p-mTOR) in the PI3K/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway of cells in two groups after 24 hours of culture, with a sample size of 3.Results:After 12 and 24 hours of culture, the proliferation activity of cells in metformin group was significantly lower than that in control group (with t values of 4.70 and 24.02, respectively, P<0.05); the proliferation activity of cells in metformin group after 24 hours of culture was significantly lower than that after 12 hours of culture within the group ( t=4.73, P<0.05). Compared with that after 12 hours of culture within the group, the proliferation inhibition rate of cells in metformin group was significantly increased after 24 hours of culture ( t=5.29, P<0.05). Compared with that in control group after 0 hour of culture, the proportion of early apoptotic cells in metformin group was significantly increased (with t values of 6.62 and 4.58, respectively, P<0.05), and the proportion of early and late apoptotic cells was significantly increased after 12 and 24 hours of culture (with t values of 4.84 and 3.75, respectively, P<0.05). After 24 hours of culture, the proportion of late apoptotic cells in metformin group was significantly higher than that after 12 hours of culture within the group ( t=4.55, P<0.05). After 12 hours of culture, the proportion of S-phase cells in metformin group was significantly lower than that in control group ( t=5.90, P<0.05). After 24 hours of culture, compared with that in control group, the proportion of G0/G1-phase cells in metformin group was significantly increased ( t=5.36, P<0.05), while the proportion of G2/M-phase cells was significantly decreased ( t=17.63, P<0.05). The proportion of S-phase cells in metformin group after 24 hours of culture was significantly higher than that after 12 hours of culture within the group ( t=7.60, P<0.05). After 24 hours of culture, 4 814 DEGs with significantly differential expression were detected in the cells of metformin group compared with control group. The significantly upregulated and downregulated DEGs were mainly involved in biological functions related to signal transduction, cell growth and death, transport and catabolism, the endocrine system, the immune system, and cancer. The pathways that were significantly enriched with DEGs with significantly differential expression included the cell cycle and DNA replication, with the highest number of genes in the PI3K/Akt signaling pathway. After 24 hours of culture, the protein expressions of PI3K, p-Akt, and p-mTOR of cells in metformin group were 0.190±0.017, 0.170±0.017, and 0.247±0.005, respectively, which were significantly lower than 0.440±0.026, 0.300±0.060, and 0.547±0.025 in control group (with t values of 13.69, 3.61, and 20.12, respectively, P values all <0.05). Conclusions:Metformin can significantly inhibit the proliferation of human keloid Fbs through the PI3K/Akt/mTOR signaling pathway and effectively induce its apoptotic process, thereby exerting antifibrotic effects.

Objective:To explore the changes in early postpartum pelvic floor muscle strength following the implementation of the new labor process.Methods:This retrospective cohort study selected 1 834 primiparous women with singleton, full-term pregnancies who delivered at Peking University First Hospital from February 2011 to March 2016 and had a pelvic floor re-examination 6-8 weeks postpartum. Out of these, 738 cases who followed the old labor process before 2014 were categorized as the old process group, and 1 096 cases who followed the new labor process after 2014 were categorized as the new process group. Basic data, childbirth information, and postpartum pelvic floor muscle strength of the two groups were compared. Data were statistically analyzed using t-test, Chi-square test, Mann-Whitney U test, Wilcoxon rank-sum test, and ordered multicategory logistic regression to assess the impact of the new and old labor process and other factors on pelvic floor muscle strength. Results:The total duration of labor, as well as the duration of the first, second, and third stages of labor, were longer in the new process group than in the old process group [549.0 min (360.0-768.0 min) vs. 482.5 min (328.0-635.0 min), 465.0 min (297.5-672.5 min) vs. 420.0 min (285.0-555.0 min), 42.0 min (24.0-74.0 min) vs. 27.0 min (18.0-45.0 min), with Z-value of－5.72,－3.95, and－9.28, all P<0.05). The rates of vaginal delivery and labor analgesia were higher in the new process group [72.1% (790/1 096) vs. 67.2% (496/738), χ2=7.41; 67.4% (739/1 096) vs. 53.4% (394/738), χ2=36.82; both P<0.05]. There were no statistically significant differences in the comparison of Class Ⅰ and Class Ⅱ muscle strength grades between the two groups (all P>0.05). Conclusion:There was no significant decline in early postpartum pelvic floor muscle strength following the implementation of the new labor process standards.

Objective:To construct an inpatient-outpatient-home step swallowing rehabilitation training program for partial laryngectomy patients.Methods:From June 2022 to May 2023, a preliminary program for inpatient-outpatient-home step swallowing rehabilitation training for partial laryngectomy patients was developed through literature search and analysis. Delphi method was used for two rounds of expert inquiry on the inpatient-outpatient-home step swallowing rehabilitation training program for partial laryngectomy patients.Results:A total of 15 experts were included for two rounds of expert inquiry. The effective response rates of the questionnaires from the two rounds of expert inquiries were 100.0% (15/15). The expert authority coefficients for the two rounds of inquiry were 0.885 and 0.855, respectively, and the Kendall harmony coefficients were 0.217 and 0.230, respectively ( P<0.01). The final inpatient-outpatient-home step swallowing rehabilitation training program for partial laryngectomy patients included three primary items (swallowing training step, swallowing training methods, and feeding guidance methods), 21 secondary items, and 35 tertiary items. Conclusions:The inpatient-outpatient-home step swallowing rehabilitation training program for partial laryngectomy patients based on the Delphi method has certain scientific and feasibility and can provide a reference for medical and nursing staff.

Abstract: Ulcerative colitis (UC) is a chronic intestinal disease caused by a variety of factors. Severe intestinal inflammation can also cause liver injury. Based on the previous research, microbial dysbiosis in the inflammatory state leads to the conversion of excess choline into trimethylamine (TMA) by the intestinal flora, which competes with the host for the use of the nutrient choline, and induces liver injury. 3, 3-dimethyl-1-butanol (DMB), a structural analogue of choline, can reduce TMA levels from choline conversion. The aim of this study was to investigate the protective effect and possible mechanism of DMB on UC and secondary liver injury. Dextran sulfate sodium-induced acute colitis model in mice was established. The weight of mice, and collected serum, liver and intestinal contents after mice sacrifice were measured. The morphological changes of colon and liver were observed; liver function was detected with the kit of biochemical indexes; UHPLC-MS/MS was applied to detect changes in choline metabolism in vivo. The experimental results showed that DMB could attenuate body weight loss index, improve colonic inflammation, and reduce liver injury in UC mice. The detection of choline-related metabolites in serum, intestinal contents and liver showed that DMB could effectively inhibit the production of trimethylamine in the intestine, improve the availability of host choline, effectively alleviate colitis deterioration, and reduce liver damage caused by severe intestinal lesions.

The tumor microenvironment includes blood vessels， lymph， nerves， non-malignant cells， and their metabolites at and near the tumor lesion site， which interact with cancer cells and promote cancer progression. Rapid proliferation of cancer cells increases oxygen consumption， or abnormalities in the structure and function of blood vessels in solid tumors lead to a decrease in oxygen supply， forming a hypoxia microenvironment. The existence of a hypoxia microenvironment is a typical pathophysiological feature of locally advanced solid tumors， widely present in various types of human malignant tumors. Hypoxia microenvironment is a sign of tumor microenvironment and an important and complex system in the breast tumor microenvironment. Its formation and development are closely related to the growth of breast cancer， occupying an important position in the research and treatment of breast cancer. With its advantages of multiple pathways and multiple targets， the effective monomer and compound of traditional Chinese medicine can better regulate the hypoxia microenvironment of breast cancer， inhibit the proliferation， invasion， and metastasis of breast cancer cells in the hypoxia environment， induce apoptosis， reverse their drug resistance， intervene in the metabolic reprogramming of breast cancer cells in the hypoxia environment， and inhibit their angiogenesis， thereby improving the quality of life of patients to a certain extent and prolonging the survival cycle of patients. This paper first summarized and discussed the effects of hypoxia microenvironment on proliferation， invasion， metastasis， drug resistance， immune function， metabolic reprogramming， non-coding RNA， iron death， and autophagy of breast cancer cells， which affected the occurrence and development of breast cancer， and it elaborated the mechanism behind it. Then， the paper elucidated the regulatory effect and mechanism of targeting the hypoxia microenvironment based on the two modes of effective monomer and compound of traditional Chinese medicine， so as to analyze and extract the deficiencies and directions of traditional Chinese medicine in regulating the hypoxia microenvironment and provide a theoretical reference for the effective treatment of breast cancer.

Backgroud At present, there is no unified standard for the detection of glufosinate ammonium and three metabolites in urine, which affects the accurate assessment of occupational exposure risk to a certain extent. It is of great significance to establish a rapid and effective inspection method to ensure occupational safety and public health. Objective To establish an ultra performance liquid chromatography-tandem mass spectrometry for simultaneous determination of glufosinate ammonium and three metabolites in urine. Methods The effects of dilution solvents and dilution ratios on the response values of glufosinate ammonium and three metabolites were compared, and the retention capacities of solid phase extraction columns for targets as well as the effects of chromatographic columns and mobile phase systems on chromatographic peaks were analyzed. Samples were quantified by matrix effect matching external standard method. Accuracy of the method was evaluated by recovery rate of standard addition, and precision of the method was evaluated by relative standard deviation of intra-day and inter-day measurements. Urine samples of 30 health individuals were collected to evaluate the application of the method. Results The urine samples were diluted with 0.2 mL water and 0.6 mL acetonitrile, purified by HLB solid phase extraction columns, and separated by Dikma Polyamino HILIC columns, and gradient elution was carried out with 0.5 mmol·L⁻¹ ammonium acetate and 0.1% ammonia water as mobile phase, which achieved a good peak shape and mass spectrum response. The linearities of the four target compounds were good in the range of 0.5-50 ng·mL⁻¹, and the correlation coefficients (r) were all greater than 0.998. The detection limits were 0.56-2.86 μg·L⁻¹, the quantification limits were 1.87-29.54 μg·L⁻¹, and the recovery rates of standard addition ranged from 75.0% to 103.6%, The relative standard deviations of intra-batch and inter-batch were from 2.5% to 8.1% and from 4.3% to 9.3% respectively. The method was applied to detect 30 urine samples of subjects, and no target was detected. Conclusion The method is simple, rapid, sensitive, and accurate. It is suitable for the determination of glufosinate ammonium and its metabolites in human urine without derivatization.