Objective To investigate the effects and mechanism of Dahuang Lingxian Prescription on bile duct reaction of cholestatic liver fibrosis rats caused by bile duct ligation.Methods A total of 40 SD rats were randomly divided into blank group,model group,ursodeoxycholic acid group and Dahuang Lingxian Prescription group,with 10 rats in each group.Except for the blank group,the remaining groups of rats underwent bile duct ligation surgery to establish a cholestatic liver fibrosis model.After surgery,the ursodeoxycholic acid group was given ursodeoxycholic acid solution by gavage,Dahuang Lingxian Prescription group was given Dahuang Lingxian Prescription solution by gavage,and the blank group and model group were given equal volume of normal saline by gavage,once a day for 3 consecutive weeks.The activities of serum AST,ALT,ALP,GGT and the contents of TBIL,TBA were tetected,the morphology of liver tissue was observed by HE staining,and the liver fibrosis was observed by Masson staining,immunohistochromic staining and Western blot were used to detect the expressions of CK19,CK7,EpCAM and SOX9 proteins.Results Compared with the blank group,the liver surface of the model group rats was rough,with a harder texture and obvious graininess,HE staining showed damage to the liver lobule structure,forming pseudo lobules,a large number of bile duct hyperplasia and inflammatory cell infiltration,and a significant increase in collagen fiber deposition(P<0.01);the activities of serum AST,ALT,ALP,GGT,as well as the contents of TBIL and TBA significantly increased(P<0.01);the positive expressions of CK19,CK7 and EpCAM in liver tissue significantly increased(P<0.01),and the protein expressions of CK19,CK7,EpCAM and SOX9 significantly increased(P<0.01).Compared with the model group,the appearance and texture of the liver of the rats in the ursodeoxycholic acid group and Dahuang Lingxian Prescription group were relatively softer,the lobular structure was less damaged,the inflammatory cells infiltration was less,the collagen fiber deposition was significantly reduced(P<0.01),the activities of serum AST,ALT,ALP,GGT,and the contents of TBIL and TBA were significantly decreased(P<0.01);the expressions of TBA and TBIL were significantly decreased(P<0.01),the positive expressions of CK19,CK7 and EpCAM significantly decreased(P<0.01),and the protein expression of CK19,CK7,EpCAM and SOX9 significantly decreased(P<0.01).Conclusion Dahuang Lingxian Prescription can inhibit the bile duct reaction associated with liver progenitor cells,decrease the expression of CK19,CK7,EpCAM and SOX9,and thus improve the cholestatic liver fibrosis of rats induced by bile duct ligation.

Objective To investigate the effects and mechanism of Dahuang Lingxian Prescription on bile duct reaction of cholestatic liver fibrosis rats caused by bile duct ligation.Methods A total of 40 SD rats were randomly divided into blank group,model group,ursodeoxycholic acid group and Dahuang Lingxian Prescription group,with 10 rats in each group.Except for the blank group,the remaining groups of rats underwent bile duct ligation surgery to establish a cholestatic liver fibrosis model.After surgery,the ursodeoxycholic acid group was given ursodeoxycholic acid solution by gavage,Dahuang Lingxian Prescription group was given Dahuang Lingxian Prescription solution by gavage,and the blank group and model group were given equal volume of normal saline by gavage,once a day for 3 consecutive weeks.The activities of serum AST,ALT,ALP,GGT and the contents of TBIL,TBA were tetected,the morphology of liver tissue was observed by HE staining,and the liver fibrosis was observed by Masson staining,immunohistochromic staining and Western blot were used to detect the expressions of CK19,CK7,EpCAM and SOX9 proteins.Results Compared with the blank group,the liver surface of the model group rats was rough,with a harder texture and obvious graininess,HE staining showed damage to the liver lobule structure,forming pseudo lobules,a large number of bile duct hyperplasia and inflammatory cell infiltration,and a significant increase in collagen fiber deposition(P<0.01);the activities of serum AST,ALT,ALP,GGT,as well as the contents of TBIL and TBA significantly increased(P<0.01);the positive expressions of CK19,CK7 and EpCAM in liver tissue significantly increased(P<0.01),and the protein expressions of CK19,CK7,EpCAM and SOX9 significantly increased(P<0.01).Compared with the model group,the appearance and texture of the liver of the rats in the ursodeoxycholic acid group and Dahuang Lingxian Prescription group were relatively softer,the lobular structure was less damaged,the inflammatory cells infiltration was less,the collagen fiber deposition was significantly reduced(P<0.01),the activities of serum AST,ALT,ALP,GGT,and the contents of TBIL and TBA were significantly decreased(P<0.01);the expressions of TBA and TBIL were significantly decreased(P<0.01),the positive expressions of CK19,CK7 and EpCAM significantly decreased(P<0.01),and the protein expression of CK19,CK7,EpCAM and SOX9 significantly decreased(P<0.01).Conclusion Dahuang Lingxian Prescription can inhibit the bile duct reaction associated with liver progenitor cells,decrease the expression of CK19,CK7,EpCAM and SOX9,and thus improve the cholestatic liver fibrosis of rats induced by bile duct ligation.

Objective:To investigate the influence of ultrasonic monitoring of bladder filling levels on setup errors before fractionated radiotherapy for cervical cancer patients through a comparative analysis, and its effectiveness in improving clinical target volume (CTV) margins.Methods:A retrospective study was conducted on 1 284 error data of setup via cone beam CT (CBCT) and 6D setup error correction system from 172 cervical cancer patients treated in the Radiotherapy Department of Peking University Cancer Hospital from January 2019 to October 2023. These patients were classified into two groups: 87 (659 times of setup) with ultrasonic monitoring of bladder filling levels and 85 (625 times of setup) without ultrasonic monitoring. The setup errors, error distributions, and numbers of abnormal setups between the two groups were compared in the lateral (Lat), longitudinal (Lng), vertical (Vrt), pitch (Pitch), roll (Roll), and rotational (Rtn) dimensions. Moreover, the CTV to planning target volume(PTV) margin values in the three-dimensional direction were calculated for both groups to assess the clinical value of ultrasonic monitoring of bladder filling levels before fractionated radiotherapy.Results:Compared to the group without ultrasonic monitoring, the group with ultrasonic monitoring exhibited lower median values of setup errors in all six-dimensional directions and smaller upper and lower interquartile ranges ( Z = -10.86 to -6.34, P<0.05). The group with ultrasonic monitoring manifested more concentrated setup errors in various directions and statistically significantly reduced numbers of abnormal setups ( χ2=15.33, P<0.05). Moreover, CTV-PTV margins of the group with ultrasonic monitoring displayed reduced CTV-PTV margin values by 0.55, 1.52, and 1.26 mm in the Vrt, Lng, and Lat directions, respectively. Conclusions:Pre-radiotherapy ultrasonic monitoring of bladder filling levels in cervical cancer patients can significantly improve the repeatability of setup, thus notably reducing the incidence of abnormal setups. Theoretically, it can narrow the range from the CTV to the PTV, thereby minimizing radiation exposure to healthy tissues and ultimately enhancing radiotherapy precision for cervical cancer and reducing radiation damage.

Objective:To investigate the influence of ultrasonic monitoring of bladder filling levels on setup errors before fractionated radiotherapy for cervical cancer patients through a comparative analysis, and its effectiveness in improving clinical target volume (CTV) margins.Methods:A retrospective study was conducted on 1 284 error data of setup via cone beam CT (CBCT) and 6D setup error correction system from 172 cervical cancer patients treated in the Radiotherapy Department of Peking University Cancer Hospital from January 2019 to October 2023. These patients were classified into two groups: 87 (659 times of setup) with ultrasonic monitoring of bladder filling levels and 85 (625 times of setup) without ultrasonic monitoring. The setup errors, error distributions, and numbers of abnormal setups between the two groups were compared in the lateral (Lat), longitudinal (Lng), vertical (Vrt), pitch (Pitch), roll (Roll), and rotational (Rtn) dimensions. Moreover, the CTV to planning target volume(PTV) margin values in the three-dimensional direction were calculated for both groups to assess the clinical value of ultrasonic monitoring of bladder filling levels before fractionated radiotherapy.Results:Compared to the group without ultrasonic monitoring, the group with ultrasonic monitoring exhibited lower median values of setup errors in all six-dimensional directions and smaller upper and lower interquartile ranges ( Z = -10.86 to -6.34, P<0.05). The group with ultrasonic monitoring manifested more concentrated setup errors in various directions and statistically significantly reduced numbers of abnormal setups ( χ2=15.33, P<0.05). Moreover, CTV-PTV margins of the group with ultrasonic monitoring displayed reduced CTV-PTV margin values by 0.55, 1.52, and 1.26 mm in the Vrt, Lng, and Lat directions, respectively. Conclusions:Pre-radiotherapy ultrasonic monitoring of bladder filling levels in cervical cancer patients can significantly improve the repeatability of setup, thus notably reducing the incidence of abnormal setups. Theoretically, it can narrow the range from the CTV to the PTV, thereby minimizing radiation exposure to healthy tissues and ultimately enhancing radiotherapy precision for cervical cancer and reducing radiation damage.

Objective:To compare and discuss the mid-to-long-term outcomes of mitral valve repair (MVP) versus biological mitral valve replacement (bMVR) in patients aged 60 years and above with rheumatic mitral valve disease.Methods:This is a retrospective cohort study. A total of 765 patients aged 60 years and older, diagnosed with rheumatic mitral valve disease and who underwent MVP or bMVR at Beijing Anzhen Hospital from January 2010 to January 2023, were retrospectively included. Among them, 186 were male and 579 were female, with an age of (66.1±4.5) years (range: 60 to 82 years). Patients were divided into two groups based on the surgical method: the mitral valve repair group (MVP group, n=256) and the bioprosthetic mitral valve replacement group (bMVR group, n=509). A 1∶1 propensity score matching was performed using a caliper value of 0.2 based on preoperative data. Paired sample t-tests, χ2 tests, or Fisher′s exact tests were used for intergroup comparisons. Kaplan-Meier method was employed to plot survival curves and valve-related reoperation rate curves for both groups before and after matching, and Log-rank tests were used to compare the mid-to long-term survival rates and valve-related reoperation rates between the two groups. Results:A total of 765 patients who completed follow-up were ultimately included, with a follow-up period ( M(IQR)) of 5.1(5.0) years (range: 1.0 to 12.9 years). After matching, each group consisted of 256 patients. The incidence of early postoperative atrial fibrillation (39.1% vs. 49.2%, χ2=4.95, P=0.026) and early mortality rates (2.0% vs. 6.2%, χ2=4.97, P=0.026) were lower in the MVP group. Unadjusted Kaplan-Meier analysis showed significantly higher 5-year and 10-year survival rates for the MVP group (92.54% vs. 83.02%, 86.22% vs. 70.19%, Log-rank: P=0.001). After adjustment with propensity scores, the Kaplan-Meier analysis still indicated higher 5-year and 10-year survival rates in the MVP group compared to the bMVR group (92.54% vs. 85.89%, 86.22% vs. 74.83%, Log-rank: P=0.024). There were no significant differences in the rates of valve-related reoperation between the two groups before and after matching (5-year and 10-year reoperation rates pre-matching: 1.75% vs. 0.57%, 5.39% vs. 7.54%, Log-rank: P=0.207; post-matching: 1.75% vs. 0, 5.39% vs. 9.27%, Log-rank: P=0.157). Conclusion:For patients aged 60 years and above with rheumatic mitral valve disease, mitral valve repair offers better mid-to-long-term survival compared to biological valve replacement.

Objective     To explore the correlation between the quantitative and qualitative features of CT images and the invasiveness of pulmonary ground-glass nodules, providing reference value for preoperative planning of patients with ground-glass nodules. Methods    The patients with ground-glass nodules who underwent surgical treatment and were diagnosed with pulmonary adenocarcinoma from September 2020 to July 2022 at the Third Affiliated Hospital of Kunming Medical University were collected. Based on the pathological diagnosis results, they were divided into two groups: a non-invasive adenocarcinoma group with in situ and minimally invasive adenocarcinoma, and an invasive adenocarcinoma group. Imaging features were collected, and a univariate logistic regression analysis was conducted on the clinical and imaging data of the patients. Variables with statistical difference were selected for multivariate logistic regression analysis to establish a predictive model of invasive adenocarcinoma based on independent risk factors. Finally, the sensitivity and specificity were calculated based on the Youden index. Results     A total of 555 patients were collected. The were 310 patients in the non-invasive adenocarcinoma group, including 235 females and 75 males, with a meadian age of 49 (43, 58) years, and 245 patients in the invasive adenocarcinoma group, including 163 females and 82 males, with a meadian age of 53 (46, 61) years. The binary logistic regression analysis showed that the maximum diameter (OR=4.707, 95%CI 2.060 to 10.758), consolidation/tumor ratio (CTR, OR=1.027, 95%CI 1.011 to 1.043), maximum CT value (OR=1.025, 95%CI 1.004 to 1.047), mean CT value (OR=1.035, 95%CI 1.008 to 1.063), spiculation sign (OR=2.055, 95%CI 1.148 to 3.679), and vascular convergence sign (OR=2.508, 95%CI 1.345 to 4.676) were independent risk factors for the occurrence of invasive adenocarcinoma (P<0.05). Based on the independent predictive factors, a predictive model of invasive adenocarcinoma was constructed. The formula for the model prediction was: Logit(P)=–1.293+1.549×maximum diameter of lesion+0.026×CTR+0.025×maximum CT value+0.034×mean CT value+0.72×spiculation sign+0.919×vascular convergence sign. The area under the receiver operating characteristic curve of the model was 0.910 (95%CI 0.885 to 0.934), indicating that the model had good discrimination ability. The calibration curve showed that the predictive model had good calibration, and the decision analysis curve showed that the model had good clinical utility. Conclusion     The predictive model combining quantitative and qualitative features of CT has a good predictive ability for the invasiveness of ground-glass nodules. Its predictive performance is higher than any single indicator.

Objective:To compare and discuss the mid-to-long-term outcomes of mitral valve repair (MVP) versus biological mitral valve replacement (bMVR) in patients aged 60 years and above with rheumatic mitral valve disease.Methods:This is a retrospective cohort study. A total of 765 patients aged 60 years and older, diagnosed with rheumatic mitral valve disease and who underwent MVP or bMVR at Beijing Anzhen Hospital from January 2010 to January 2023, were retrospectively included. Among them, 186 were male and 579 were female, with an age of (66.1±4.5) years (range: 60 to 82 years). Patients were divided into two groups based on the surgical method: the mitral valve repair group (MVP group, n=256) and the bioprosthetic mitral valve replacement group (bMVR group, n=509). A 1∶1 propensity score matching was performed using a caliper value of 0.2 based on preoperative data. Paired sample t-tests, χ2 tests, or Fisher′s exact tests were used for intergroup comparisons. Kaplan-Meier method was employed to plot survival curves and valve-related reoperation rate curves for both groups before and after matching, and Log-rank tests were used to compare the mid-to long-term survival rates and valve-related reoperation rates between the two groups. Results:A total of 765 patients who completed follow-up were ultimately included, with a follow-up period ( M(IQR)) of 5.1(5.0) years (range: 1.0 to 12.9 years). After matching, each group consisted of 256 patients. The incidence of early postoperative atrial fibrillation (39.1% vs. 49.2%, χ2=4.95, P=0.026) and early mortality rates (2.0% vs. 6.2%, χ2=4.97, P=0.026) were lower in the MVP group. Unadjusted Kaplan-Meier analysis showed significantly higher 5-year and 10-year survival rates for the MVP group (92.54% vs. 83.02%, 86.22% vs. 70.19%, Log-rank: P=0.001). After adjustment with propensity scores, the Kaplan-Meier analysis still indicated higher 5-year and 10-year survival rates in the MVP group compared to the bMVR group (92.54% vs. 85.89%, 86.22% vs. 74.83%, Log-rank: P=0.024). There were no significant differences in the rates of valve-related reoperation between the two groups before and after matching (5-year and 10-year reoperation rates pre-matching: 1.75% vs. 0.57%, 5.39% vs. 7.54%, Log-rank: P=0.207; post-matching: 1.75% vs. 0, 5.39% vs. 9.27%, Log-rank: P=0.157). Conclusion:For patients aged 60 years and above with rheumatic mitral valve disease, mitral valve repair offers better mid-to-long-term survival compared to biological valve replacement.

Objective By investigating the retention and fatigue performance of polyetheretherketone(PEEK)clasps with increased proportions of clasp arm engaging the undercut,an innovative method to improve PEEK clasps'performance was proposed and verified.Methods Three groups of PEEK clasps(n=10/group)with the terminal 1/3,2/3 and whole of their retentive arms engaging the 0.75 mm undercut were designed and fabricated respectively along with a group of cobalt-chrome clasps(n=10)with their terminal 1/3 of retentive arms engaging the 0.25 mm undercut.Retentive forces were recorded initially and every 1 500 cycles for a total of 15 000 in-sertion and removal fatigue cycles.Optical scanning and software analysis were applied to evaluate the deformation of the clasps by root mean square(RMS)after fatigue test.The inner surface morphology of clasps'arms was observed by scanning electron microscopy.Re-sults PEEK clasps with the whole of their retentive arms engaging the undercut exhibited highest mean retentive force(9.24±1.78)Namong other PEKK clasps,which was slightly lower than that of cobalt-chrome clasps(11.88±2.05)N.The retentive force of each group turned out to be reduced after fatigue cycles and cobalt-chrome clasps showed the greatest reduction(38.38%).The RMS of the PEEK clasps groups were of no statistical difference(P=0.111)and were lower than that of cobalt-chrome clasps(105.47±10.82)μm.Evidence of surface abrasion was observed on all groups of clasps especially on the section that engaged the undercut.Conclusion Increasing the proportion of PEEK clasp arm engaging the undercut effectively improved the retentive force and satisfied clinical re-quirements after fatigue cycles.PEEK clasps exhibited greater retention stability than cobalt-chrome clasps.It is feasible to improve the performance of PEEK clasps by increasing the proportion of clasp arm engaging the undercut.

Objective:To discuss the effect of sialic acid-binding immunoglobulin-like lectin-15(Siglec15)derived from M2 tumor-associated macrophages(M2-TAMs)on promoting the malignant biological behavior of the esophageal squamous cell carcinoma(ESCC)through bioinformatics analysis,and to validate the findings through cell experiment.Methods:The Tumor Immune Estimation Resource(TIMER)online Database was used to analyze the expression differences and immune infiltration of Siglec15 in pan-cancer and adjacent normal tissues.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of Siglec15 mRNA in M2-TAMs and ESCC EC109 and KYSE150 cells.Based on the non-contact co-culture of M2-TAMs and ESCC cells,the following groups were set up,such as EC109/KYSE150 group,EC109/KYSE150+si-NC group(transfected with si-NC sequence),and EC109/KYSE150+si-Siglec15 group(transfected with si-Siglec15#1 and si-Siglec15#2 sequences).CCK-8 method was used to detect the proliferation activities of the cells in various groups;wound healing assay was used to detect the wound healing rates of the cells in various groups;Transwell chamber assay was used to detect the numbers of migration and invasion cells in various groups;flow cytometry was used to detect the apoptotic rates of the cells in various groups.Results:The bioinformatics analysis results showed that compared with adjacent normal tissue,the expression levels of Siglec15 mRNA in pan-cancer tissues such as esophageal cancer,colon cancer,and head and neck squamous cell carcinoma tissues were increased(P＜0.05 or P＜0.01),and the expression level of Siglec15 mRNA in esophageal cancer tissue was significantly positively correlated with the infiltration of the macrophages(P＜0.05).Compared with the EC109 cells and KYSE150 cells,the expression level of Siglec15 mRNA in M2-TAMs was significantly increased(P＜0.01).There was no significant difference in the proliferation rate of the cells among EC109/KYSE150 group,EC109/KYSE150+si-NC group,and EC109/KYSE150+si-Siglec15 group(P＞0.05).Compared with EC109/KYSE150 group,after treated for 24 and 48 h,the wound healing rate of the cells in EC109/KYSE150+si-NC group was increased(P＜0.01),the numbers of migration and invasion cells were increased(P＜0.05),and the apoptotic rate was decreased(P＜0.01).Compared with EC109/KYSE150+si-NC group,the wound healing rates of the cells in EC109/KYSE150+si-Siglec15#1 group and EC109/KYSE150+si-Siglec15#2 group were decreased(P＜0.05),the numbers of migration and invasion cells were decreased(P＜0.05),and the apoptotic rates of the cells had no significant difference(P＞0.05).Conclusion:Siglec15 derived from M2-TAMs may be a key factor in promoting the migration and invasion of the ESCC cells.

FLASH radiotherapy (FLASH-RT) has garnered considerable attention globally in recent years. Compared to conventional radiotherapy, FLASH-RT can deliver the total radiation dose to the target volume in an extremely short time, reducing the radiation-induced damage to normal tissue while maintaining similar anti-tumor effects. FLASH-RT has been in the clinical trial stage, with several clinical research result being reported. Based on the collected global clinical research result of FLASH-RT in recent years, this study systematically reviewed FLASH-RT′s safety, radiation-related side effects, treatment efficacy, opportunities, and challenges in clinical trials.