Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

Among tumor microenvironment (TME), the entire metabolic characteristics of tumor-resident cells are reprogrammed to benefit the expansion of tumor cells, which count on glutamine in large part to fuel the tricarboxylic acid cycle for energy generation and anabolic metabolism support. Endothelial cells that are abducted by tumor cells to form a pathological tumor vascular network for constructing the hypoxic immunosuppressive TME, also rely on glutaminolysis as the "engine" of angiogenesis. Additionally, the glutamine metabolic preference benefits the polarization of TAMs towards pro-tumoral M2 phenotype as well. Herein, we developed a type of siRNA micelleplexes (MH@siGLS1) to reverse immunosuppressive TME by targeting glutaminolysis within tumor-resident cells for tumor vasculature normalization- and TAMs repolarization-enhanced photo-immunotherapy. Tumor cell starvation and antioxidant system destruction achieved by MH@siGLS1-mediated glutaminolysis inhibition could promote photodynamic therapy efficacy, which was available to trigger immunogenic cell death for adaptive antitumor immune responses. Meanwhile, glutaminolysis inhibition of tumor endothelial cells and TAMs could realize tumor vascular normalization and TAMs repolarization for antitumor immunity amplification. This study provides a unique perspective on cancer treatments by focusing on the interrelations of metabolic characteristics and the biofunctions of various cell types within TME.

OBJECTIVES: To construct an intelligent analysis model for classifying fetal orientation during intrapartum ultrasound videos based on multi-feature fusion. METHODS: The proposed model consists of the Input, Backbone Network and Classification Head modules. The Input module carries out data augmentation to improve the sample quality and generalization ability of the model. The Backbone Network was responsible for feature extraction based on Yolov8 combined with CBAM, ECA, PSA attention mechanism and AIFI feature interaction module. The Classification Head consists of a convolutional layer and a softmax function to output the final probability value of each class. The images of the key structures (the eyes, face, head, thalamus, and spine) were annotated with frames by physicians for model training to improve the classification accuracy of the anterior occipital, posterior occipital, and transverse occipital orientations. RESULTS: The experimental results showed that the proposed model had excellent performance in the tire orientation classification task with the classification accuracy reaching 0.984, an area under the PR curve (average accuracy) of 0.993, and area under the ROC curve of 0.984, and a kappa consistency test score of 0.974. The prediction results by the deep learning model were highly consistent with the actual classification results. CONCLUSIONS The multi-feature fusion model proposed in this study can efficiently and accurately classify fetal orientation in intrapartum ultrasound videos.
Humans ; Female ; Ultrasonography, Prenatal/methods* ; Pregnancy ; Fetus/diagnostic imaging* ; Neural Networks, Computer ; Video Recording

Temporomandibular joint (TMJ) disc displacement is one of the most significant subtypes of temporomandibular joint disorders, but its etiology and mechanism are poorly understood. In this study, we elucidated the mechanisms by which destruction of inflamed collagen fibrils induces alterations in the mechanical properties and positioning of the TMJ disc. By constructing a rat model of TMJ arthritis, we observed anteriorly dislocated TMJ discs with aggravated deformity in vivo from five weeks to six months after a local injection of Freund's complete adjuvant. By mimicking inflammatory conditions with interleukin-1 beta in vitro, we observed enhanced expression of collagen-synthesis markers in primary TMJ disc cells cultured in a conventional two-dimensional environment. In contrast, three-dimensional (3D)-cultivated disc cell sheets demonstrated the disordered assembly of inflamed collagen fibrils, inappropriate arrangement, and decreased Young's modulus. Mechanistically, inflammation-related activation of the nuclear factor kappa-B (NF-κB) pathway occurs during the progression of TMJ arthritis. NF-κB inhibition reduced the collagen fibril destruction in the inflamed disc cell sheets in vitro, and early NF-κB blockade alleviated collagen degeneration and dislocation of the TMJ discs in vivo. Therefore, the NF-κB pathway participates in the collagen remodeling in inflamed TMJ discs, offering a potential therapeutic target for disc displacement.
Animals ; NF-kappa B/metabolism* ; Temporomandibular Joint Disorders/pathology* ; Temporomandibular Joint Disc/metabolism* ; Rats ; Rats, Sprague-Dawley ; Disease Models, Animal ; Male ; Collagen/metabolism* ; Cells, Cultured ; Joint Dislocations/pathology* ; Interleukin-1beta ; Arthritis, Experimental

Objective:To compare the efficacy of posteromedial combined with lateral Frosch approach versus anterior medial and lateral dual incision approach in open reduction and internal fixation for Schatzker type VI tibial plateau fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 41 patients with Schatzker type VI tibial plateau fractures, who were admitted to the 940th Hospital of the Joint Logistics Support Force of the PLA from January 2018 to May 2024, including 23 males and 18 females, aged 34-79 years [(50.7±7.7)years]. Twenty-three patients underwent open reduction and internal fixation via the posteromedial combined with lateral Frosch approach (posterior approach group), while 18 patients underwent the same procedure via the anterior medial and lateral dual incision approach (anterior approach group). The following parameters were compared between the two groups: operation duration, intraoperative blood loss, postoperative drainage volume, depth of articular surface depression and tibial plateau width measured preoperatively, at 7 days, 3 months postoperatively, and at the last follow-up, medial proximal tibial angle (MPTA) and posterior proximal tibial angle (PPTA) measured at 7 days, 3 months postoperatively, and at the last follow-up, visual analogue scale (VAS) scores assessed preoperatively, at 7 days postoperatively, and at the last follow-up, American Knee Society (KSS) score and knee flexion range of motion assessed at 7 days, 3 months postoperatively, and at the last follow-up, fracture healing status at the last follow-up, and incidence of postoperative complications.Results:All the patients were followed up for 12-16 months [(14.3±2.1)months]. The operation duration was (119.6±11.8)minutes in the posterior approach group, which was significantly shorter than (140.3±10.6)minutes in the anterior approach group ( P<0.05). There were no statistically significant differences in intraoperative blood loss or postoperative drainage volume between the two groups ( P>0.05). No significant differences were found in the preoperative depth of articular surface depression or tibial plateau width between the two groups ( P>0.05). At 7 days, 3 months postoperatively, and at the last follow-up, the depth of articular surface depression was 0.8(0.6, 1.0)mm, 0.6(0.5, 0.8)mm, and 0.6(0.5, 0.7)mm in the posterior approach group, which were significantly shorter than 1.1(0.9, 1.3)mm, 0.8(0.7, 1.0)mm, and 0.8(0.7, 1.0)mm in the anterior approach group ( P<0.05). The tibial plateau width at the same time points was 71.0(69.1, 73.5)mm, 70.5(69.2, 72.9)mm, and 70.5(69.3, 72.5)mm in the posterior approach group, which were significantly shorter than 73.0(72.3, 74.2)mm, 71.5(71.0, 73.0)mm, and 71.5(71.1, 72.6)mm in the anterior approach group ( P<0.05). At 7 days, 3 months postoperatively, and at the last follow-up, the MPTA values were (87.4±0.7)°, (87.7±0.6)°, and (87.9±0.5)° in the posterior approach group, which were significantly larger than (85.2±2.5)°, (86.0±2.2)°, and (86.3±2.0)° in the anterior approach group ( P<0.01). The PPTA values at the same time points were (9.5±0.7)°, (9.0±0.5)°, and (8.6±0.4)° in the posterior approach group, which were significantly smaller than (11.2±1.0)°, (10.3±0.8)°, and (9.8±0.7)° in the anterior approach group ( P<0.01). There was no significant difference in the preoperative VAS score between the two groups ( P>0.05). At 7 days postoperatively and at the last follow-up, the VAS scores were 4.0(3.0, 5.0)points and 0.5(0.0, 2.0)points in the posterior approach group, which were significantly lower than 5.0(4.0, 5.0)points and 1.0(1.0, 3.0)points in the anterior approach group ( P<0.05). At 7 days, 3 months postoperatively, and at the last follow-up, the KSS scores were 62.5(57.0, 67.5)points, 75.5(72.0, 82.5)points, and 87.0(82.5, 93.5)points in the posterior approach group, which were significantly higher than 61.5(54.5, 63.0)points, 74.0(68.0, 79.0)points, and 85.5(78.0, 88.5)points in the anterior approach group ( P<0.05). The knee flexion range of motion was 90.0(85.0, 95.0)°, 115.0(109.0, 122.0)°, and 126.0(120.0, 130.0)° in the posterior approach group, which were significantly greater than 80.5(75.2, 85.8)°, 110.0(104.0, 115.0)°, and 119.0(113.0, 122.0)° in the anterior approach group ( P<0.05). At the last follow-up, all the fractures were healed in both groups. No statistically significant difference was found in the incidence of postoperative complications between the two groups ( P>0.05). Conclusion:Compared to the anterior medial and lateral dual incision approach, the posteromedial combined with lateral Frosch approach demonstrates superior advantages in operation duration, reduction quality, pain relief, functional recovery in the treatment of Schatzker type VI tibial plateau fractures, while the incidence of complications is comparable.

Objective To investigate the value of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)parameters in evaluating the short-term prognosis of laryngeal cancer patients after postoperative radiotherapy.Methods A case-control study was performed on 127 laryngeal cancer patients admitted to our hospital from January 2021 to December 2023.The patients underwent different tumor treatment followed by radical radiotherapy.According to tumor recurrence or not,they were divided into a recurrence group(n=50)and a non-recurrence group(n=77).DCE-MRI parameters,such as volume transfer constant(Ktrans),rate constant(Kep),and volume fraction of extracellular extravascular space(Ve),and clinical data were compared between the 2 groups.Multivariate logistic regression analysis was used to identify influencing factors for short-term prognosis after radiotherapy.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive efficacy of DCE-MRI parameters,and the area under the curve(AUC)was calculated.Results The recurrence group had significantly larger proportions of positive surgical margins,preoperative maximum lesion diameter≥4 cm,ulcerative lesions,stages N1～N3,and advanced stages Ⅲ～Ⅳ,and obviously higher Ktrans and Kep values but lower Ve valus than the non-recurrence group(P<0.05).Multivariate logistic regression analysis indicated that positive surgical margins,stages N1～N3,Ktrans,and Kep were independent risk factors for short-term prognosis,while Ve was a protective factor(P<0.05).ROC curve analysis showed that the AUC value of combination of Ktrans,Kep and Ve and of above 5 indicators in predicting short-term prognosis of postoperative radiotherapy for laryngeal cancer was 0.920(95%CI:0.858～0.961)and 0.923(95%CI:0.862～0.963),respectively.Though the AUC value of combined 3 parameters was significantly higher than that of the single indicator alone(P<0.05),there was no difference in the value between the combination of 3 parameters and the combined application of the 5 indicators.Conclusion DCE-MRI parameters Ktrans,Kep,and Ve are closely associated with short-term prognosis of postoperative radiotherapy for laryngeal cancer.Their combination has a good predictive efficacy for the short-term prognosis of the patients.

Objective: To investigate the status quo and associated factors of drinking water knowledge, attitude and behavior among primary school students in rural areas, so as to provide evidence for health behavioral intervention of drinking water in primary school. Methods: Twentythree primary schools in rural area from Hebei, Henan, Shandong and Shanxi provinces were selected by using purposive sampling method from March 1 to April 27 in 2023. Selfdesigned questionnaires regarding knowledge, attitude and behavior of drinking water were distributed to all students in grade 3-6, and 2 173 valid questionnaires were obtained. Multivariate Logistic regression was used to analyze the influencing factors of drinking water knowledge, attitude and behavior of primary school students. Results: The attainment rates of drinking water knowledge, attitude and behavior level were 20.02%, 26.65%, and 31.20%, respectively, among primary school students. The median of daily water intake was 1 000 mL, and the average daily water intake was (1 172.99±771.89)mL. In addition, 66.31% of students water intake reached the minimum standard of 800 mL recommended. The results of multiple Logistic regression indicated that drinking water accessibility in school, health education of drinking water, and individual selfcontrol ability were positively correlated with the knowledge (OR=1.31, 1.57, 1.58), attitude (OR=2.07, 1.65, 1.73), behavior (OR=1.40, 1.49, 1.91) of drinking water and daily water intake (OR=1.41, 1.38, 1.20) (P<0.05). Conclusions Primary school students in rural areas are generally lack of appropriate health awareness on drinking water including knowledge, attitude and behavior. Schools should take targeted measures to focus on the cultivation of students selfcontrol ability, so as to improve students knowledge and attitudes of drinking water, and furthermore help students shape their healthy behaviors of drinking water.

Objective:To develop the Nurse Parenting Stress Scale and evaluate its reliability and validity.Methods:Based on Abidin's Parenting Stress Theory, scale items were generated through literature review and semi-structured interviews. The initial version was constructed via Delphi expert consultation. Using a convenience sampling method, nurses from six hospitals in Shandong Province were surveyed between August and October 2024. The first survey collected 314 questionnaires (308 valid, effective recovery rate 98.1%) for item analysis and exploratory factor analysis (EFA). The second survey collected 458 questionnaires (447 valid, effective recovery rate 97.6%) for confirmatory factor analysis (CFA) .Results:The Nurse Parenting Stress Scale consists of 4 dimensions and 31 items. The Cronbach's α coefficient of the total scale was 0.951, split-half reliability was 0.782, and test-retest reliability was 0.926. EFA extracted four common factors explaining 70.241% of the cumulative variance. CFA demonstrated a good model fit. The item-level content validity index ( I- CVI) ranged from 0.889 to 1.000, the scale-level universal agreement content validity index ( S- CVI/ UA) was 0.903, and the scale-level average content validity index ( S- CVI/ Ave) was 0.989. Conclusions:The Nurse Parenting Stress Scale shows strong reliability and validity and can serve as an effective tool for assessing parenting stress among nurses.

Objective:To analyze the short-term efficacy and safety of robot-assisted laparoscopic partial nephrectomy（RAPN）for non-metastatic pathological stage T 3a renal cell carcinoma. Methods:The clinical and pathological data of 45 patients with pathologically confirmed non-metastatic T 3a renal cell carcinoma who underwent RAPN at Sun Yat-sen University Cancer Center between January 2016 and December 2023 were retrospectively reviewed. There were 30 males and 15 females. The average age of the cohort was（54.3±10.7）years，and the average clinical tumor diameter was（4.9±1.8）cm. Of all the patients，35（77.8%）were asymptomatic，7（15.6%）presented with hematuria，and 3（6.7%）presented with lumbar pain. Preoperative imaging assessed 34 patients（75.6%）as having clinical stage T 3a，all suspected of involving the collecting system or perirenal fat invasion；the remaining 11 patients（24.4%）were assessed as having stage T 1-2 disease. The median R.E.N.A.L. nephrectomy score was 8.0（7.0，10.0）. A history of hypertension，diabetes，or chronic kidney disease was present in 18 patients（40.0%）. The primary endpoint was progression-free survival，and the secondary endpoints included postoperative complications and short-term renal function outcomes. Survival curve was estimated using the Kaplan-Meier method，and renal function comparisons were made using the paired t-test. Results:The RAPN was performed through a transabdominal approach in 32 patients（71.1%），with a median estimated blood loss of 150.0（50.0，300.0）ml. Seven（15.6%）patients required intraoperative blood transfusion. The median length of postoperative hospital stay was 4.0（4.0，6.0）days. Postoperative complications occurred in 6 patients（13.3%），including 5（11.1%）with mild complications and 1（2.2%）with a severe complication. Renal function returned to baseline in 24 of 39 evaluable patients（61.5%），while 3 patients（7.7%）developed surgery-related chronic kidney disease 3 to 12 months postoperatively，but none required dialysis. The median follow-up time was 31.8（22.7，50.9）months，12（26.7%）patients received programmed cell death protein 1 inhibitor adjuvant therapy postoperatively. During follow-up，3 patients experienced tumor recurrence，the 3-year progression-free survival rate of the entire cohort was 95.4%.Conclusions:For some carefully selected patients with T 3a renal cell carcinoma，RAPN performed by experienced surgeons is a feasible and safe option，providing excellent short-term oncological outcomes，complication control，and renal function recovery. The long-term efficacy remains to be seen.

Objective:To develop a simple and effective subretinal injection pipeline system to enhance the accuracy and precision of subretinal injection volume control.Methods:A retrospective case series study. From May to October 2023, 18 patients (18 eyes) with submacular hemorrhage (SMH) who continuously received modified subretinal injection treatment in Department of Ophthalmology of Peking Union Medical College Hospital were included in the study. Among them, there were 10 males and 8 females. The mean age was (60.00±7.41) years. The primary causes included polypoid choroidal vasculopathy (14 cases), retinal macroaneurysm (2 cases), traumatic retinopathy (1 case), and Valsalva retinopathy (1 case). Hemorrhage affected 14 eyes of the fovea centralis. All affected eyes underwent standard three-channel 25G vitrectomy via the flat part of the ciliary body combined with modified subretinal injection of recombinant tissue plasminogen activator. The improved injection system consisted of a 1 ml syringe, a Q-Syte TM connector, a 41G subretinal microinjection needle, a converter and a viscoelastic substance control pipeline. The drug preparation time for subretinal injection (i.e., the time consumed by the system connection step), the injection time, whether bubbles occur during the injection process, and the perioperative complications were recorded and analyzed. Results:The preparation time prior to drug injection ranged from 230 to 335 seconds, while the injection completion time varied between 43 and 75 seconds. Both times decreased progressively as operator proficiency improved. Among the treated eyes, five received a target injection dose of 0.05 ml and thirteen received 0.10 ml, with all eyes achieving the preset dose accurately. No subretinal bubbles were observed during the injection procedure. Additionally, no intraoperative complications such as retinal hemorrhage or tear secondary to mechanical trauma at the injection site were recorded. Postoperatively, one eye developed anterior chamber hemorrhage, which resolved following intraocular pressure-lowering treatment. No other postoperative complications, including hemorrhage, rhegmatogenous retinal detachment, or infection, were observed in the remaining eyes.Conclusion:The retinal drug injection system developed in this study has a simple structure, safe and stable operation, can achieve precise drug injection, and effectively avoid the formation of bubbles.