Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

Total knee arthroplasty(TKA)is mainly used for the treatment of advanced knee osteoarthritis.Accurate preoperative planning and rapid prosthesis recognition are essential for smooth operation and postoperative rehabilitation.However,manual prosthesis recognition rely on doctors'experience,easily leading to misdiagnosis or missed diagnosis.Recent years,artificial intelligence(AI)had been integrated with medical imaging,represented by machine learning(ML)and its branch deep learning(DL),and displayed relatively powerful auxiliary functions in TKA.The research status and application progresses of AI combined with imaging in TKA were reviewed in this article.

Salvia miltiorrhiza is a perennial herb of the genus Salvia(Lamiaceae). As one of the earliest medicinal plants to undergo molecular biology research, it has gradually become a model plant for molecular biology of medicinal plants. With the gradual analysis of the genome of S. miltiorrhiza and the biosynthetic pathways of its main active components tanshinone and salvianolic acids, the transcriptional regulation mediated by transcription factors and related regulatory proteins has gradually become a new research focus. Due to the lack of scientific and unified naming of transcription factors and different research indexes in different literature, this paper systematically sorted out the transcription factors in different literature with the genomes of DSS3 from selfing for three generations and bh2-7 from selfing for six generations as reference. In total, 73 transcription factors and related regulatory proteins belonging to 13 gene families were identified. The effects of overexpression or gene silencing experiments on tanshinone and salvianolic acids were also analyzed. This study unified the identified transcription factors, which laid a foundation for further constructing the regulatory networks of secondary metabolites and insect or stress resistance and improving the quality of medicinal materials by using global transcriptional regulation engineering.
Salvia miltiorrhiza/chemistry* ; Plant Proteins/metabolism* ; Gene Expression Regulation, Plant ; Transcription Factors/metabolism* ; Abietanes/metabolism*

OBJECTIVE: To determine risk factors for cutout failure in geriatric intertrochanteric fracture patients after cephalomedullary nail fixation. METHODS: A retrospective review of 518 elderly patients who underwent cephalomedullary nail fixation for intertrochanteric fractures between January 2008 and August 2018 was conducted, including 167 males and 351 females, age from 65 to 97 years old. All patients were followed up for at least one year after surgery and divided into a healed group and a cutout group based on whether the hip screw cutout occurred. Among all patients, 10 cases experienced hip screw cutout. The general information, surgical data, and radiological data of the two groups were compared, and risk factors influencing hip screw cutout were analyzed. Propensity score matching was then performed on the cutout group based on gender, age, body mass index(BMI), and American Society of Anesthesiologists(ASA), and 40 patients from the healed group were matched at a ratio of 1∶4. Key risk factors affecting hip screw cutout were further analyzed. Multivariable logistic regression analysis was conducted to evaluate associations between variables and cutout failure. RESULTS: There were no statistically significant differences between the healed group and the cutout group in terms of age, gender, BMI, ASA, and AO classification. However, statistically significant differences were observed between the two groups in terms of reduction quality(P=0.003) and tip-apex distance(TAD), P<0.001. Multivariate analysis identified poor reduction quality OR=23.138, 95%CI(2.163, 247.551), P=0.009 and TAD≥25 mm OR=30.538, 95%CI(2.935, 317.770), P=0.004 as independent risk factors for cutout failure. CONCLUSION The present study identified poor reduction quality and TAD≥25 mm as factors for cutout failure in geriatric intertrochanteric fractures treated with cephalomedullary nails. Further studies are needed to calculate the optimal TAD for cephalomedullary nails.
Humans ; Male ; Female ; Hip Fractures/surgery* ; Aged, 80 and over ; Aged ; Risk Factors ; Retrospective Studies ; Fracture Fixation, Intramedullary/adverse effects* ; Bone Nails ; Bone Screws

OBJECTIVE: To explore the co-morbid influencing factors of postmenopausal osteoporosis(PMOP) and dyslipidemia, and to provide evidence-based basis for clinical co-morbidity management. METHODS: Based on the 2017 to 2018 Beijing community cross-sectional survey data, PMOP patients were included and divided into the dyslipidemia group and the uncomplicated dyslipidemia group according to whether they were comorbid with dyslipidemia. Demographic characteristics, living habits and disease history were collected through questionnaires, and bone mineral density and bone metabolism biomarkers (osteocalcin, blood calcium, serum typeⅠprocollagen N-terminal prepeptide, etc.) were detected on site. Co-morbidity risk factors were analyzed using binary logistic regression. RESULTS: Three hundred and twenty patients with PMOP were included, including the comorbid group (75 patients) and the uncomplicated group (245 patients). The results showed that history of cardiovascular disease [OR=1.801, 95%CI(1.003, 3.236), P=0.049], history of cerebrovascular disease [OR=2.923, 95%CI(1.460, 5.854), P=0.002], frying and cooking methods[OR=5.388, 95%CI(1.632, 17.793), P=0.006], OST results[OR=0.910, 95%CI(0.843, 0.983), P=0.016], and blood Ca results [OR=60.249, 95%CI(1.862, 1 949.926), P=0.021] were the influencing factors of PMOP complicated with dyslipidemia. CONCLUSION Focus should be placed on the influencing factors of PMOP and dyslipidemia co-morbidities, with emphasis on multidimensional assessment, combining lifestyle interventions with bone metabolism marker monitoring to optimize co-morbidity management.
Humans ; Dyslipidemias/epidemiology* ; Female ; Middle Aged ; Osteoporosis, Postmenopausal/metabolism* ; Aged ; Cross-Sectional Studies ; Risk Factors ; Bone Density

Objective To explore the influences of long-chain noncoding RNA DHRS4-AS1 (lncRNA DHRS4-AS1) on the proliferation, invasion, migration, and apoptosis of thyroid cancer (TC) cells by regulating the microRNA-221-3p (miR-221-3p)/suppressor of cytokine signaling 3 (SOCS3) signaling axis. Methods Quantitative real-time PCR (qRT-PCR) was applied to detect the expression of lncRNA DHRS4-AS1, miR-221-3p, and SOCS3 mRNA in TC cell lines, and the optimal cell line was selected for subsequent experiments. FTC-133 cells were divided into five groups: control group, pcDNA-NC group, DHRS4-AS1 group, DHRS4-AS1 combined with agomir NC group, and DHRS4-AS1 combined with miR-221-3p-agomir group. Transfection efficiency was assessed using qRT-PCR. Dual luciferase reporter assays were applied to verify the targeting interaction between lncRNA DHRS4-AS1, SOCS3, and miR-221-3p. Western blot analysis was used to detect the expression of SOCS3 in FTC-133 cells. EdU method was used to measure cell proliferation. Flow cytometry was applied to measure the apoptosis of FTC-133 cells. Scratch experiment was applied to measure the migration of FTC-133 cells. Transwell chamber was applied to detect the invasion of FTC-133 cells. Nude mouse transplantation tumor experiment was used to observe the effect of lncRNA DHRS4-AS1 on the growth of TC transplantation tumors. Results Dual luciferase reporter assays showed a targeting relationship between lncRNA DHRS4-AS1, miR-221-3p, and SOCS3. LncRNA DHRS4-AS1 and SOCS3 were downregulated and miR-221-3p was upregulated in FTC-133 cells. Overexpression of lncRNA DHRS4-AS1 inhibited proliferation, migration, and invasion of FTC-133 cells, while inducing apoptosis. Conversely, miR-221-3p overexpression reversed these inhibitory effects, and suppressed the apoptosis. Nude mouse transplantation experiment observed that overexpression of lncRNA DHRS4-AS1 resulted in a decrease in tumor tissue quality and volume, and a decrease in miR-221-3p expression and an increase in SOCS3 expression. Conclusion LncRNA DHRS4-AS1 is downregulated in FTC-133 cells. Overexpression of lncRNA DHRS4-AS1 can inhibit the proliferation, invasion, and migration of TC cells and induce apoptosis by regulating the miR-221-3p/SOCS3 signaling axis.
MicroRNAs/metabolism* ; Suppressor of Cytokine Signaling 3 Protein/metabolism* ; Humans ; RNA, Long Noncoding/metabolism* ; Apoptosis/genetics* ; Cell Proliferation/genetics* ; Cell Movement/genetics* ; Thyroid Neoplasms/physiopathology* ; Animals ; Signal Transduction/genetics* ; Cell Line, Tumor ; Mice, Nude ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic ; Mice ; Mice, Inbred BALB C

To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion is one of the most commonly used supportive treatments for children with hematological diseases. This guideline provides guidance and recommendations for blood transfusions in children with aplastic anemia, thalassemia, autoimmune hemolytic anemia, glucose-6-phosphate dehydrogenase deficiency, acute leukemia, myelodysplastic syndromes, immune thrombocytopenic purpura, and thrombotic thrombocytopenic purpura. This article presents the evidence and interpretation of the blood transfusion provisions for children with hematological diseases in the "Guideline for pediatric transfusion", aiming to assist in the understanding and implementing the blood transfusion section of this guideline.
Humans ; Child ; Hematologic Diseases/therapy* ; Blood Transfusion/standards* ; Practice Guidelines as Topic