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.

Accurate description of dose distribution in tumor radiotherapy is essential for the development and evaluation of treatment plans, aiming to improve the prognosis and reduce complications of radiotherapy patients. Traditional dosimetric models are often based on dose-volume histograms; however, this model can result in the loss of dose distribution and texture information in the treatment plan. Dosiomics is a rapidly developing research field that provides a new direction for analyzing information such as dose distribution and texture. This article reviews studies related to dosiomics, aiming to explore its current development status, limitations, and clinical value in radiotherapy.

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.

In recent years, the roles of mitochondrial RNA and its associated human diseases have been reported to increase significantly. Treatments based on mtRNA metabolic processes and nuclear gene mutations are thus discussed. The mitochondrial oxidative phosphorylation process is affected by mtRNA metabolism, including mtRNA production, maturation, stabilization, and degradation, which leads to a variety of inherited human mitochondrial diseases. Moreover, mitochondrial diseases are caused by mitochondrial messenger RNA, mitochondrial transfer RNA, and mitochondrial ribosomal RNA gene mutations. This review presents the molecular mechanisms of human mtRNA metabolism and pathological mutations in mtRNA metabolism-related nuclear-encoded/nonencoded genes and mitochondrial DNA mutations to highlight the importance of mitochondrial RNA-related diseases and treatments.
Humans ; Mitochondrial Diseases/therapy* ; RNA, Mitochondrial ; RNA/genetics* ; Mitochondria/genetics* ; Mutation/genetics* ; RNA, Transfer/genetics* ; DNA, Mitochondrial/genetics*

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 investigate the impacts of nuclear receptor-interacting protein 1(NRIP1)on sepsis-evoked intesti-nal epithelial injury via transcriptional regulation of high mobility group box 1(HMGB1).Methods:The expression levels of NRIP1 and HMGB1 were detected by RT-qPCR and Western blot.The pathological changes of intestinal tissue were detected by HE staining.CCK-8 assay determined the optimal treatment time of LPS.Caco-2 cells were transfected with NRIP1 small interfering RNA(siRNA-NRIP1-1/2),and cell viability and apoptosis were detected by CCK-8 assay and flow cytometry,respectively.RT-qPCR and Western blot examined the expressions of inflammation-associated factors.Transepithelial resistance(TEER)was used to detect intestinal epi-thelial permeability.Western blot was used to detect the expressions of apoptosis and tight-junction related proteins.The binding rela-tionship between NRIP1 and HMGB1 was verified by luciferase reporting assay and chromatin immunoprecipitation assay(ChIP).After knocking down NRIP1 and overexpressing HMGB1 in LPS-treated Caco-2 cells,the functional experiment was performed again.Results:NRIP1 expression was fortified in the intestinal tissues of sepsis rats and LPS-treated Caco-2 cells.Interference with NRIP1 attenuated LPS-elicited Caco-2 cell viability injury,apoptosis,inflammatory response and barrier damage.Additionally,NRIP1 might activate HMGB1 expression at transcriptional level and HMGB1 elevation might reverse the impacts of NRIP1 absence on Caco-2 cell viability,apoptosis,inflammatory response as well as barrier function.Conclusion:NRIP1 may promote sepsis-elicited intestinal epi-thelial injury,which may be related to transcriptional activation of HMGB1.

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 impacts of nuclear receptor-interacting protein 1(NRIP1)on sepsis-evoked intesti-nal epithelial injury via transcriptional regulation of high mobility group box 1(HMGB1).Methods:The expression levels of NRIP1 and HMGB1 were detected by RT-qPCR and Western blot.The pathological changes of intestinal tissue were detected by HE staining.CCK-8 assay determined the optimal treatment time of LPS.Caco-2 cells were transfected with NRIP1 small interfering RNA(siRNA-NRIP1-1/2),and cell viability and apoptosis were detected by CCK-8 assay and flow cytometry,respectively.RT-qPCR and Western blot examined the expressions of inflammation-associated factors.Transepithelial resistance(TEER)was used to detect intestinal epi-thelial permeability.Western blot was used to detect the expressions of apoptosis and tight-junction related proteins.The binding rela-tionship between NRIP1 and HMGB1 was verified by luciferase reporting assay and chromatin immunoprecipitation assay(ChIP).After knocking down NRIP1 and overexpressing HMGB1 in LPS-treated Caco-2 cells,the functional experiment was performed again.Results:NRIP1 expression was fortified in the intestinal tissues of sepsis rats and LPS-treated Caco-2 cells.Interference with NRIP1 attenuated LPS-elicited Caco-2 cell viability injury,apoptosis,inflammatory response and barrier damage.Additionally,NRIP1 might activate HMGB1 expression at transcriptional level and HMGB1 elevation might reverse the impacts of NRIP1 absence on Caco-2 cell viability,apoptosis,inflammatory response as well as barrier function.Conclusion:NRIP1 may promote sepsis-elicited intestinal epi-thelial injury,which may be related to transcriptional activation of HMGB1.