BACKGROUND:Currently,there are many modeling methods for pelvic organ prolapse animal models,and the commonly used methods are vaginal balloon dilatation,oophorectomy and the combination of the two.There is no study comparing the three modeling methods in detail.OBJECTIVE:To construct and validate a rat animal model of pelvic organ prolapse using three different methods and to identify the advantages and disadvantages of various models.METHODS:Seventy-two 8-week SPF-grade female Sprague-Dawley rats were selected and randomly divided into four groups,namely,vaginal balloon dilatation group,ovariectomy group,ovariectomy combined with vaginal balloon dilatation group(the combined group),and the sham-operated group(no ovariectomy and no vaginal dilatation).The vaginal wall tissues of rats were collected at 4,8 and 12 weeks after the operation for hematoxylin-eosin staining,Masson staining,EVG staining and immunohistochemical staining of α-smooth muscle actin,Vimentin and matrix metalloproteinase 9 detection,and the pelvic floor muscle tissues were taken at 4,8 and 12 weeks after the operation for hematoxylin-eosin staining,Masson staining and EVG staining.RESULTS AND CONCLUSION:(1)Hematoxylin-eosi staining showed that there was no significant difference in the decrease of vaginal epithelial layer thickness in the vaginal balloon dilatation group compared with the sham-operated group,(P＞0.05),while the thickness of the vaginal epithelial layer was significantly reduced in the ovariectomy group and the ovariectomy combined with vaginal balloon dilation group(P＜0.001),and the reduction was more significant in the ovariectomy combined with vaginal balloon dilation group,remained stable at 8 weeks after surgery and lasted until 12 weeks.(2)The changes in the content of collagen fibers and elastic fibers in the vaginal wall stained by Masson and EVG staining were the same as the changes in the thickness of the vaginal epithelial layer stained by hematoxylin-eosin,and there were no changes in collagen fibers and elastic fibers in the pelvic floor muscle tissues of the treatment groups.(3)At 4,8 and 12 weeks after treatment,there was no significant difference in the expression levels of α-smooth muscle actin,Vimentin and matrix metalloproteinase 9 in the vaginal wall tissue of the balloon dilation group compared with the control group(P＞0.05),whereas the expression levels of α-smooth muscle actin and Vimentin were significantly decreased in the ovariectomy group and ovariectomy combined with vaginal balloon dilation group(P＜0.01)and the expression of matrix metalloproteinase 9 showed a significant increase(P＜0.01),with a more pronounced increase in the ovariectomy combined with vaginal balloon dilation group,and the increase reached a stable state at 8 weeks after surgery and could persist up to 12 weeks.To conclude,vaginal balloon dilatation could not maintain the degeneration of pelvic organ prolapse formed by the vaginal wall for a long period,and both ovariectomy and the combined method can be used.Ovariectomy combined with vaginal balloon dilatation can significantly accelerate and aggravate the formation of typical histological features of pelvic organ prolapse in vaginal wall tissues,effectively shorten the experimental period,and improve the efficiency.These effects reach a stable state at 8 weeks after surgery and can be sustained up to 12 weeks,which is practical and convenient for the study of pelvic organ prolapse animal models.

BACKGROUND:Currently,there are many modeling methods for pelvic organ prolapse animal models,and the commonly used methods are vaginal balloon dilatation,oophorectomy and the combination of the two.There is no study comparing the three modeling methods in detail.OBJECTIVE:To construct and validate a rat animal model of pelvic organ prolapse using three different methods and to identify the advantages and disadvantages of various models.METHODS:Seventy-two 8-week SPF-grade female Sprague-Dawley rats were selected and randomly divided into four groups,namely,vaginal balloon dilatation group,ovariectomy group,ovariectomy combined with vaginal balloon dilatation group(the combined group),and the sham-operated group(no ovariectomy and no vaginal dilatation).The vaginal wall tissues of rats were collected at 4,8 and 12 weeks after the operation for hematoxylin-eosin staining,Masson staining,EVG staining and immunohistochemical staining of α-smooth muscle actin,Vimentin and matrix metalloproteinase 9 detection,and the pelvic floor muscle tissues were taken at 4,8 and 12 weeks after the operation for hematoxylin-eosin staining,Masson staining and EVG staining.RESULTS AND CONCLUSION:(1)Hematoxylin-eosi staining showed that there was no significant difference in the decrease of vaginal epithelial layer thickness in the vaginal balloon dilatation group compared with the sham-operated group,(P＞0.05),while the thickness of the vaginal epithelial layer was significantly reduced in the ovariectomy group and the ovariectomy combined with vaginal balloon dilation group(P＜0.001),and the reduction was more significant in the ovariectomy combined with vaginal balloon dilation group,remained stable at 8 weeks after surgery and lasted until 12 weeks.(2)The changes in the content of collagen fibers and elastic fibers in the vaginal wall stained by Masson and EVG staining were the same as the changes in the thickness of the vaginal epithelial layer stained by hematoxylin-eosin,and there were no changes in collagen fibers and elastic fibers in the pelvic floor muscle tissues of the treatment groups.(3)At 4,8 and 12 weeks after treatment,there was no significant difference in the expression levels of α-smooth muscle actin,Vimentin and matrix metalloproteinase 9 in the vaginal wall tissue of the balloon dilation group compared with the control group(P＞0.05),whereas the expression levels of α-smooth muscle actin and Vimentin were significantly decreased in the ovariectomy group and ovariectomy combined with vaginal balloon dilation group(P＜0.01)and the expression of matrix metalloproteinase 9 showed a significant increase(P＜0.01),with a more pronounced increase in the ovariectomy combined with vaginal balloon dilation group,and the increase reached a stable state at 8 weeks after surgery and could persist up to 12 weeks.To conclude,vaginal balloon dilatation could not maintain the degeneration of pelvic organ prolapse formed by the vaginal wall for a long period,and both ovariectomy and the combined method can be used.Ovariectomy combined with vaginal balloon dilatation can significantly accelerate and aggravate the formation of typical histological features of pelvic organ prolapse in vaginal wall tissues,effectively shorten the experimental period,and improve the efficiency.These effects reach a stable state at 8 weeks after surgery and can be sustained up to 12 weeks,which is practical and convenient for the study of pelvic organ prolapse animal models.

OBJECTIVE: To review the role and research progress of mechanotransduction signaling pathway in distraction osteogenesis, so as to provide theoretical basis and reference for clinical treatment. METHODS: The role and research progress of mechanotransduction signaling pathway in distraction osteogenesis were summarized by extensive review of relevant literature at home and abroad. RESULTS: The mechanotransduction signaling pathway plays a central role of "sensation-transformation-execution" in distraction osteogenesis, and activates a series of molecular mechanisms to promote the regeneration and remodeling of bone tissue by integrating external mechanical signals. Mechanical stimuli are converted into mechanotransduction signals through the perception of integrins, Piezo1 ion channels and bone cell networks. Activate downstream molecules are transduce through signal pathways such as Wnt/β-catenin, transforming growth factor β/bone morphogenetic protein-Smad, mitogen-activated protein kinase, protein kinase Hippo-Yes-associated protein/transcriptional coactivator with PDZ-binding motif, and phosphatidylinositol 3-kinase/ protein kinase B, so as to achieve the effects of promoting osteoblasts proliferation, accelerating endochondral ossification, regulating bone resorption and the like, thereby promoting the regeneration of new bone in the distraction area. The study of mechanotransduction signaling pathways in distraction osteogenesis is expected to optimize the mechanical parameters of distraction osteogenesis and provide targeted intervention strategies for accelerating new bone regeneration and mineralization in the distraction zone. However, the specific mechanism of mechanotransduction signaling pathway in distraction osteogenesis remains to be further elucidated, and artificial intelligence and multi-omics analysis may be the future development direction of mechanotransduction signaling pathway. CONCLUSION In distraction osteogenesis, mechanotransduction signal transduction is the core mechanism of bone regeneration in the distraction zone, which regulates cell behavior and tissue regeneration by converting mechanical stimulation into biochemical signals.
Mechanotransduction, Cellular/physiology* ; Osteogenesis, Distraction/methods* ; Humans ; Signal Transduction ; Bone Regeneration ; Animals ; Osteoblasts/metabolism* ; Osteogenesis ; Transforming Growth Factor beta/metabolism* ; Ion Channels/metabolism* ; Integrins/metabolism* ; beta Catenin/metabolism* ; Bone Morphogenetic Proteins/metabolism* ; Smad Proteins/metabolism*

Objective:To evaluate the effect of the radiation dose of thoracic cage bone structure on clinical prognosis in patients with locally advanced non‐small cell lung cancer (LA‐NSCLC) receiving chemoradiotherapy, and to develop and verify a combined model combining the radiation dose of bone structure, the estimated radiation dose of immune cells (EDRIC) and other related factors to predict the prognosis of LA‐NSCLC.Methods:Clinical data of 197 patients with LA‐NSCLC who underwent chemoradiotherapy were retrospectively analyzed. All patients were randomly divided into the training set and testing set at a ratio of 7:3 using computer random partitioning. The EDRIC value was calculated using the model developed by Jin et al. and modified by Ladbury et al. The scope of the thoracic cage structure includes the ribs, sternal manubrium, sternal body, thoracic vertebral body, thoracic vertebral appendages, and thoracic vertebrae. The tumor volume, ERDIC, and average bone structure dose (D mean) were categorized into two groups using the P25, P50, P75 value from the quartile method. Univariate and multivariate Cox proportional hazards regression were used to analyze the influencing factors of overall survival (OS), local progression‐free survival (LPFS), and distant metastasis‐free survival (DMFS) for predicting the outcome, and significant correlated variables were retained to construct a combined prediction model with EDRIC. The receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and calibration curves were plotted for subjects at the 2‐year time point of the combined model to evaluate the predictive performance. The model was visualized through a nomograph. Results:In the thoracic cage bone structure, D mean > 47.3 Gy of the sternal manubrium was an independent risk factor of OS, LPFS, and DMFS of LA-NSCLC patients. D mean > 23.1 Gy of thoracic vertebral body was an independent risk factor of OS, and D mean > 14.4 Gy of thoracic vertebral body was an independent risk factor of DMFS. Among other variables, gross tumor volume (GTV) >50.2 cm 3 was a risk factor for OS, and GTV >87.0 cm 3 was a risk factor for LPFS. Planning target volume >571.9 cm 3 was a risk factor for DMFS. A combined prediction model for OS, LPFS, and DMFS was established with EDRIC using features significantly associated with these three predicted outcomes. The area under the ROC curve (AUC) of OS combined model in the training set and test set were 0.708 and 0.696, respectively, and the AUC of DMFS combined model were 0.675 and 0.639, respectively. The calibration curve and DCA curve of the two prediction endpoints showed that the combined model had good prediction accuracy and clinical benefit. However, the LPFS model was not good in accuracy and clinical applicability. Conclusions:The radiation dose of sternal manubrium and thoracic vertebral body in the thoracic cage bone structure is an independent influencing factor for the prognosis of LA‐NSCLC patients after chemoradiotherapy. The combined model has good predictive performance for OS and DMFS.

OBJECTIVE To investigate the frailty status of elderly patients with acquired immune deficiency syn-drome(AIDS)and opportunistic infection,and to analyze the associated risk factors.METHODS A convenience sampling method was used to survey 210 elderly patients with AIDS and opportunistic infection in Guangzhou from May 2024 to Apr.2025.General information questionnaires,FRAIL scale,Nutritional Risk Screening 2002,Athens Insomnia Scale and objective biological indicators were utilized to investigate the incidence of frailty.Logis-tic regression analysis was employed to identify the risk factors for frailty in elderly patients with AIDS and oppor-tunistic infection.RESULTS Among the 210 elderly patients with AIDS and opportunistic infection,40(19.05％)were frail,including 20(15.62％)patients aged＜60 years and 20(24.39％)≥60 years.Advanced age(OR=1.111,95％CI:1.033-1.194,P=0.004),body mass index(BMI)≥ 24.0 kg/m2(OR=4.329,95％CI:1.008-18.1585,P=0.049),hemoglobin level(OR=1.037,95％CI:1.009-1.065,P=0.009)and CD4+T lymphocyte count＜200(OR=10.792,95％CI:1.358-85.765,P=0.024)were identified as risk factors for frailty.Regular exercise(OR=0.108,95％CI:0.032-0.362,P＜0.001)was found to be a protective factor.CONCLUSIONS Elderly patients with AIDS and opportunistic infection experience early onset and high inci-dence of frailty,influenced by multiple factors.Early intervention,enhanced nutrition and engaging in regular ex-ercise can reduce the occurrence of frailty.

OBJECTIVE To investigate the frailty status of elderly patients with acquired immune deficiency syn-drome(AIDS)and opportunistic infection,and to analyze the associated risk factors.METHODS A convenience sampling method was used to survey 210 elderly patients with AIDS and opportunistic infection in Guangzhou from May 2024 to Apr.2025.General information questionnaires,FRAIL scale,Nutritional Risk Screening 2002,Athens Insomnia Scale and objective biological indicators were utilized to investigate the incidence of frailty.Logis-tic regression analysis was employed to identify the risk factors for frailty in elderly patients with AIDS and oppor-tunistic infection.RESULTS Among the 210 elderly patients with AIDS and opportunistic infection,40(19.05％)were frail,including 20(15.62％)patients aged＜60 years and 20(24.39％)≥60 years.Advanced age(OR=1.111,95％CI:1.033-1.194,P=0.004),body mass index(BMI)≥ 24.0 kg/m2(OR=4.329,95％CI:1.008-18.1585,P=0.049),hemoglobin level(OR=1.037,95％CI:1.009-1.065,P=0.009)and CD4+T lymphocyte count＜200(OR=10.792,95％CI:1.358-85.765,P=0.024)were identified as risk factors for frailty.Regular exercise(OR=0.108,95％CI:0.032-0.362,P＜0.001)was found to be a protective factor.CONCLUSIONS Elderly patients with AIDS and opportunistic infection experience early onset and high inci-dence of frailty,influenced by multiple factors.Early intervention,enhanced nutrition and engaging in regular ex-ercise can reduce the occurrence of frailty.

Objective:To evaluate the effect of the radiation dose of thoracic cage bone structure on clinical prognosis in patients with locally advanced non‐small cell lung cancer (LA‐NSCLC) receiving chemoradiotherapy, and to develop and verify a combined model combining the radiation dose of bone structure, the estimated radiation dose of immune cells (EDRIC) and other related factors to predict the prognosis of LA‐NSCLC.Methods:Clinical data of 197 patients with LA‐NSCLC who underwent chemoradiotherapy were retrospectively analyzed. All patients were randomly divided into the training set and testing set at a ratio of 7:3 using computer random partitioning. The EDRIC value was calculated using the model developed by Jin et al. and modified by Ladbury et al. The scope of the thoracic cage structure includes the ribs, sternal manubrium, sternal body, thoracic vertebral body, thoracic vertebral appendages, and thoracic vertebrae. The tumor volume, ERDIC, and average bone structure dose (D mean) were categorized into two groups using the P25, P50, P75 value from the quartile method. Univariate and multivariate Cox proportional hazards regression were used to analyze the influencing factors of overall survival (OS), local progression‐free survival (LPFS), and distant metastasis‐free survival (DMFS) for predicting the outcome, and significant correlated variables were retained to construct a combined prediction model with EDRIC. The receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and calibration curves were plotted for subjects at the 2‐year time point of the combined model to evaluate the predictive performance. The model was visualized through a nomograph. Results:In the thoracic cage bone structure, D mean > 47.3 Gy of the sternal manubrium was an independent risk factor of OS, LPFS, and DMFS of LA-NSCLC patients. D mean > 23.1 Gy of thoracic vertebral body was an independent risk factor of OS, and D mean > 14.4 Gy of thoracic vertebral body was an independent risk factor of DMFS. Among other variables, gross tumor volume (GTV) >50.2 cm 3 was a risk factor for OS, and GTV >87.0 cm 3 was a risk factor for LPFS. Planning target volume >571.9 cm 3 was a risk factor for DMFS. A combined prediction model for OS, LPFS, and DMFS was established with EDRIC using features significantly associated with these three predicted outcomes. The area under the ROC curve (AUC) of OS combined model in the training set and test set were 0.708 and 0.696, respectively, and the AUC of DMFS combined model were 0.675 and 0.639, respectively. The calibration curve and DCA curve of the two prediction endpoints showed that the combined model had good prediction accuracy and clinical benefit. However, the LPFS model was not good in accuracy and clinical applicability. Conclusions:The radiation dose of sternal manubrium and thoracic vertebral body in the thoracic cage bone structure is an independent influencing factor for the prognosis of LA‐NSCLC patients after chemoradiotherapy. The combined model has good predictive performance for OS and DMFS.

The classical prescription Yangweitang， derived from Zhengzhi Zhunsheng， is specialized in treating syndromes of chill and fever due to exogenous pathogens， inner-cooling， and malaria， and it has been included in the Catalogue of Ancient Classical Formulas （the First Batch） published by the National Administration of Traditional Chinese Medicine （TCM） in 2018. Through bibliographical research， the relevant ancient books and modern documents were systematically sorted out， and it was found that there were many prescriptions related to the Yangweitang from Zhengzhi Zhunsheng. They were interwoven with Yangweitang from Zhengzhi Zhunsheng and widely used in clinical practice. In order to clarify their history and evolution， this paper combed the historical origin of Yangweitang and its related prescriptions and conducted textual analysis on key information such as semantic composition， herb origin， processing method， and efficacy. A total of 896 pieces of data on Yangweitang from Zhengzhi Zhunsheng were collected. 26 pieces of effective data were included after the screening， involving 17 ancient TCM books. Then， a total of 28 pieces of data on prescriptions related to the Yangweitang from Zhengzhi Zhunsheng were included， involving 23 ancient TCM books for reference. The textual analysis showed that Yangweitang originated from the Renshen Yangweitang recorded in Taiping Huimin Heji Jufang in the Song dynasty. Based on the original formula， medical experts from later generations have modified it into many different versions. A comparative analysis showed that Yangweitang from different generations had similar compositions， and the herb origin and processing method were basically clear. The recommended prescriptions are as follows： 37.3 g of Pinelliae Rhizoma Praeparatum Cum Alumine， Magnoliae Officinalis Cortex（fried with ginger juice）， and frying with rice water Atractlodis Rhizoma， 27.98 g of Citri Exocarpium Rubrum， 18.65 g of Pogostemon cablin leaf， Tsaoko Fructus， Poria， and Ginseng Radix et Rhizoma， and 9.33 g of Glycyrrhizae Radix et Rhizoma. They could be ground into a coarse powder， with 14.92 g for every dose， and they could be orally taken after being decocted with 450 mL of water， 7 g of fresh ginger， and 2 g of Mume Fructus to 270 mL in warm conditions. Yangweitang from Zhengzhi Zhunsheng has the effect of warming the middle and releasing the external， and it can treat many syndromes including spleen and stomach disharmony caused by chill and fever due to exogenous pathogens and inner-cooling， as well as all kinds of malaria. Modern clinical applications mainly focus on chronic atrophic gastritis and other digestive system diseases.

Objective:To analyze the failure mode after immunotherapy and the prognostic significance of combined radiotherapy for advanced non-small cell lung cancer (NSCLC).Methods:Clinical data of 220 advanced NSCLC patients receiving immune checkpoint inhibitors (ICI) as the first-line therapy in Tianjin Medical University Cancer Institute and Hospital from January 2017 to December 2021 were retrospectively analyzed. The baseline characteristics, the first-line treatment regimen, modes and locations of failure, radiotherapy purpose, location and prescription dose of all patients were collected. The main parameter was the overall survival (OS). Survival analysis was conducted by Kaplan-Meier method. Survival comparison was performed by log-rank test.Results:A total of 220 patients were enrolled in the study in which 65 cases (29.5%) exhibited a state of oligometastasis. Among 72 patients who received radiotherapy, 29 cases (40%) received chest radiotherapy and 53 cases (74%) received metastatic radiotherapy. The median follow-up time was 25.6 months. Up to the last follow-up, disease progression had been observed in 140 patients, with 84 patients (38.2%) of them demonstrating a state of oligometastasis. Among 120 patients with disease progression and confirmed location of progression, 62 patients (51.7%) failed in first-line immunotherapy because of the primary lesion progression (mainly in the chest cavity), 34 patients (28.3%) due to the appearance of new metastases, and the remaining 24 patients(20.0%) due to primary lesion progression and new distant metastases. Among 72 patients treated with the first-line immunotherapy combined with local radiotherapy, 17 patients (24%) received planned radiotherapy, another 17 patients (24%) received salvage radiotherapy, and the remaining 38 patients (53%) received radiotherapy to relieve symptoms. The prognosis of patients significantly differed according to the purpose of radiotherapy ( P=0.030). The median OS of patients who did not receive radiotherapy was 29.1 months, those who received planned radiotherapy did not reach the median OS, and the median OS of those who received salvage radiotherapy was 28.7 months, and the median OS of those who received local radiotherapy to relieve symptoms was only 19.0 months. Conclusions:The progression of primary lesions is the main failure mode of the first-line immunotherapy. Chest cavity is the main location of tumor progression. Local radiotherapy for intrathoracic lesions may improve the survival benefit further for advanced NSCLC patients after the first-line immunotherapy.

Objective:To evaluate the value of whole-brain radiotherapy (WBRT) combined with simultaneous integrated boost (SIB) and WBRT plus sequential stereotactic radiosurgery (SRS) in the treatment of small-cell lung cancer (SCLC) patients with brain metastases (BM).Methods:A retrospective analysis was performed among 135 SCLC patients with BM who were admitted to Tianjin Medical University Cancer Institute and Hospital from 2007 to 2023. They all received cisplatin- or carboplatin-based first-line chemotherapy and WBRT with 94 patients receiving thoracic radiotherapy after chemotherapy. All patients were divided into the WBRT+SIB ( n=66) and WBRT+SRS groups ( n=69) according to the treatment methods. After propensity score matching (PSM), 63 patients were assigned into each group. The primary endpoints were overall survival (OS) and brain metastasis-related local control (BMRLC) rates. Categorical data, such as gender and age, were compared by Chi-square test. OS and BMRLC were calculated by Kaplan-Meier method. The survival curves between two groups were compared by log-rank test. The risk factors of OS and BMRLC were assessed by multivariate Cox regression models. Results:In all the patients, the median follow-up time was 24.9 (range 6.30-109.57) months. The 2-year OS and BMRLC rates were 49.0% and 85.0%, respectively. Cerebral necrosis occurred in 2 patients. Multivariate analysis revealed that shorter time interval of BM after diagnosis (≤10 months) ( P=0.041), control of extracranial progression ( P=0.029), and lower diagnosis-specific graded prognostic assessment (DS-GPA) (≥2) ( P=0.006) significantly improved OS. After PSM, the 2-year OS rate in the WBRT+SIB group was significantly higher than that in the WBRT+SRS group ( P=0.041), while the 2-year BMRLC rate was not significantly improved ( P=0.203). In the DS-GPA<2 subgroup, the OS in the WBRT+SIB group was significantly higher than that in the WBRT+SRS group ( P=0.016), whereas no significant difference was observed in BMRLC between two groups ( P=0.205). In the DS-GPA≥2 subgroup, no significant difference was found in OS between two groups ( P=0.266), while BMRLC in the WBRT+SIB group was significantly lower compared with that in the WBRT+SRS group ( P=0.027). Conclusions:WBRT+SIB is more suitable for SCLC patients with BM than WBRT+SRS. However, WBRT+SRS yields higher local control for DS-GPA≥2 patients.