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Background The survival of pancreatic cancer patients remains poor. However, the underlying molecular mechanism and new therapeutic target of pancreatic cancer are still needed to be found. Many studies have shown that the IGF2 mRNA-binding protein 2 (IGF2BP2) plays oncogenic roles in cancers. However, the clinical significance, role and molecular mechanisms of IGF2BP2 in pancreatic cancer remain unclear. Methods The expression of IGF2BP2 and miR-141 was detected in pancreatic cancer, and clinical significances were analyzed by statistical analysis. The function of IGF2BP2 and miR-141 was determined in vitro and in vivo, and the underlying mechanism was investigated. The gene copy number variation (CNV) of IGF2BP2 was analyzed based on The Cancer Genome Atlas (TCGA) dataset. microRNAs (miRNAs) regulating IGF2BP2 were predicted by online tools and confirmed by experiments. Results IGF2BP2 is overexpressed in pancreatic cancer tissues compared with control tissues. Upregulation of IGF2BP2 predicts shorter overall survival (OS) in pancreatic cancer patients by statistical analysis. IGF2BP2 overexpression is partially due to genomic amplification. Bioinformatics analyses and validation experiments showed that IGF2BP2 is a direct target of miR-141. A negative correlation between IGF2BP2 mRNA expression and the expression of miR-141 was observed in pancreatic cancer tissues and more importantly, reexpression of miR-141 rescued the oncogenic role of IGF2BP2. Moreover, upregulating IGF2BP2 expression promotes pancreatic cancer cell growth by activating the PI3K/Akt signaling pathway in vitro and in vivo. Conclusions We comprehensively reveal the oncogenic role of IGF2BP2 in pancreatic cancer carcinogenesis and confirm that genomic amplification and the silencing of miR-141 contribute to its activation. Our findings highlight that IGF2BP2 may be a promising molecular target for the treatment of pancreatic cancer.

Background Osteosarcoma (OS) is the most common primary malignant bone tumor occurring in children and young adults. Drug-resistant osteosarcoma often results in chemotherapy failure. Therefore, new treatments aimed at novel therapeutic targets are urgently needed for the treatment of drug-resistant osteosarcoma. Mitochondria-targeted phototherapy, i.e., synergistic photodynamic/photothermal therapy, has emerged as a highly promising strategy for treating drug-resistant tumors. This study proposed a new nano-drug delivery system based on near-infrared imaging and multifunctional graphene, which can target mitochondria and show synergistic phototherapy, with preferential accumulation in tumors. Methods and results Based on our previous study, (4-carboxybutyl) triphenyl phosphonium bromide (TPP), a mitochondria-targeting ligand, was conjugated to indocyanine green (ICG)-loaded, polyethylenimine-modified PEGylated nanographene oxide sheets (TPP-PPG@ICG) to promote mitochondrial accumulation after cellular internalization. Thereafter, exposure to a single dose of near-infrared irradiation enabled synergistic photodynamic and photothermal therapy, which simultaneously inhibited adenosine triphosphate synthesis and mitochondrial function. Induction of intrinsic apoptosis assisted in surmounting drug resistance and caused tumor cell death. After fluorescence imaging-guided synergistic phototherapy, the mitochondria-targeting, multifunctional graphene-based, drug-delivery system showed highly selective anticancer efficiency in vitro and in vivo, resulting in marked inhibition of tumor progression without noticeable toxicity in mice bearing doxorubicin-resistant MG63 tumor cells. Conclusion The mitochondria-targeting TPP-PPG@ICG nanocomposite constitutes a new class of nanomedicine for fluorescence imaging-guided synergistic phototherapy and shows promise for treating drug-resistant osteosarcoma.

Background The relationship between preoperative sleep quality and postoperative clinical outcomes after total joint arthroplasty (TJA) is unclear. We performed a prospective cohort study to determine whether preoperative sleep quality was correlated with postoperative outcomes after TJA. Methods In this prospective cohort study, 994 patients underwent TJA. Preoperative sleep measures included scores on the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), and a ten-point sleep quality scale. The primary study outcome measured was the visual analog scale (VAS) pain score to 12 weeks postoperation. The consumption of analgesic rescue drugs (oxycodone and parecoxib) and postoperative length of stay (LOS) were recorded. We also measured functional parameters, including range of motion (ROM), Knee Society Score (KSS), and Harris hip score (HHS). Results The mean age for total knee and hip arthroplasties was 64.28 and 54.85 years, respectively. The PSQI scores were significantly correlated with nocturnal and active pain scores and ROM and functional scores from postoperative day 1 (POD1) to POD3. In addition, significant correlation was noted between the correlation between the active pain scores and ESS scores in the TKA group at postoperative 3 months. The consumption of analgesics after joint arthroplasty was significantly correlated with the PSQI scores. Moreover, significant correlations were noted between the sleep parameters and postoperative length of hospital stay (LOS). Conclusion Preoperative sleep parameters were correlated with clinical outcomes (i.e., pain, ROM, function, and LOS) after TJA. Clinicians should assess the sleep quality and improve it before TJA.

Objectives Residual varus after total knee arthroplasty (TKA) can affect functional outcomes, which may worsen in the presence of obesity. However, no studies were found to compare the outcomes of obese patients involving postoperative residual mild varus or neutral. The aim of this study was to compare postoperative complications and prosthesis survival, and functional outcomes for knees of obese patients with neutral or mild varus after TKA. Methods We retrospectively reviewed 188 consecutive obese patients (body mass index ≥30 kg/m2) at our hospital who underwent TKA due to varus knee osteoarthritis from January 2010 to December 2015. The mechanical hip‐knee‐ankle axis angle was measured in all patients at admission and discharge. Knee functions were retrospectively assessed based on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Knee Society Knee Score (KS‐KS), Knee Society Function Score (KS‐FS), Forgotten Joint Score (FJS), and range of motion (ROM). Continuous data were compared between knees with neutral or mild varus alignment using analysis of Student's t test or variance or the Kruskal–Wallis test as appropriate. For multiple comparisons of outcomes, we used Bonferroni–Dunn method to adjust p‐values. Categorical data were compared using the chi‐squared test. Results Of the 156 knees in 137 obese patients who completed follow‐up for a mean of 8.32 ± 1.47 years, 97 knees were corrected from varus to neutral and 54 knees were kept in mild residual varus. Patients with mild varus knees had significantly WOMAC (8.25 ± 8.637 vs. 14.97 ± 14.193, p = 0.009) and better FJS (86.03 ± 15.607 vs. 70.22 ± 30.031, p = 0.002). The two types of knees did not differ significantly in KS‐KS, KS‐FS, or ROM. Although one patient with a neutral knee had to undergo revision surgery, there was no significant difference between two groups. Conclusions For obese patients with osteoarthritis, preservation of residual varus alignment after TKA can improve functional outcomes without compromising prosthesis survival. Our study found that knees with mild varus showed significantly better joint functional scores in obese patients. For obese patients, preservation of residual varus alignment can improve functional outcomes without compromising prosthesis survival.

Femoral nerve blocks (FNB) can provide effective pain relief but result in quadriceps weakness with increased risk of falls following total knee arthroplasty (TKA). Adductor canal block (ACB) is a relatively new alternative providing pure sensory blockade with minimal effect on quadriceps strength. The meta-analysis was designed to evaluate whether ACB exhibited better outcomes with respect to quadriceps strength, pain control, ambulation ability, and complications. PubMed, Embase, Web of Science, Wan Fang, China National Knowledge Internet (CNKI) and the Cochrane Database were searched for RCTs comparing ACB with FNB after TKAs. Of 309 citations identified by our search strategy, 12 RCTs met the inclusion criteria. Compared to FNB, quadriceps maximum voluntary isometric contraction (MVIC) was significantly higher for ACB, which was consistent with the results regarding quadriceps strength assessed with manual muscle strength scale. Moreover, ACB had significantly higher risk of falling versus FNB. At any follow-up time, ACB was not inferior to FNB regarding pain control or opioid consumption, and showed better range of motion in comparison with FNB. ACB is superior to the FNB regarding sparing of quadriceps strength and faster knee function recovery. It provides pain relief and opioid consumption comparable to FNB and is associated with decreased risk of falls.

Aberrant expression of miR-30d is associated with the development and progression of several human cancers. However, its biological roles and underlying mechanisms in pancreatic cancer are largely unknown. The expression of miR-30d in pancreatic cancer was evaluated in public databases and further valuated by real-time quantitative PCR, western blot, and immunohistochemistry in a cohort of pancreatic cancer patients. The role of miR-30d in the proliferation and metastasis of pancreatic cancer cells was determined using in vitro and in vivo assays. Bioinformatics analyses were performed to examine potential target genes of miR-30d. Luciferase reporter assay and functional rescue experiments were used to elucidate the mechanisms of miR-30d. miR-30d was found frequently decreased in pancreatic cancer compared with nontumor tissues, and downregulation of miR-30d predicted poor prognosis and early relapse of pancreatic cancer patients. Overexpression of miR-30d significantly repressed the growth and metastasis of pancreatic cancer cells both in vitro and in vivo. Bioinformatics analyses identified sex-determining region Y-box 4 (SOX4) as a target gene of miR-30d. Mechanically, miR-30d exerted its tumor suppressive effect by directly targeting SOX4, which caused inhibition of the PI3K-AKT signaling pathway. Overexpression of SOX4 partially antagonized the inhibitory effects of miR-30d. Our study demonstrated that dysregulation of the miR-30d/SOX4/PI3K-AKT axis promotes the development and progression of pancreatic cancer. These findings suggest miR-30d as a promising and reliable therapeutic target for pancreatic cancer.

Purpose The body mass index (BMI) is widely recognized as a prognostic factor in multiple operations; however, the relationship between the BMI and outcomes following total knee arthroplasty (TKA) is extensively debated. We aimed to evaluate the effect of the BMI at different cutoff values on the outcomes following primary TKA. Methods Electronic databases (PubMed/Medline, CENTRAL, Embase and Web of Science) were systematically searched for studies investigating the association between the BMI and outcomes following primary TKA. Two investigators independently reviewed studies for eligibility, assessed the study quality using the Newcastle-Ottawa Scale and extracted the data. A meta-analysis was performed using Review Manager software. Results Twenty-eight articles including a total of 20,988 TKAs were identified. The postoperative Knee Society Score appeared to trend lower in obese (BMI ≥ 30 kg/m 2 ) patients than in non-obese (BMI < 30 kg/m 2 ) patients. The meta-analysis showed that revision with follow-up ≥5 years, any infection, superficial infection and deep vein thrombosis occurred statistically more frequently in obese patients, whereas a deep infection occurred statistically more frequently in morbidly obese (BMI ≥ 40 kg/m 2 ) patients than in non-obese patients. No differences in aseptic loosening with follow-up ≥5 years, pulmonary embolism and perioperative mortality rates were found between obese and non-obese patients. Conclusions Patients with a BMI ≥ 30 kg/m 2 are at a higher risk of lower functional scores and developing complications following primary TKA. It appears reasonable to encourage obese patients to lose weight before selective TKA. Level of evidence Prognostic study, Level III.

Investor sentiment has a profound impact on financial market volatility; however, it is difficult to accurately capture the complex nonlinear relationships among sentiment proxies with the existing methods. In this study, we propose a novel investor sentiment indicator, SGAN, which uses generative adversarial networks (GANs) to extract the nonlinear latent structure from eight sentiment proxies from February 2003 to September 2023 in the Chinese A-share market. Unlike traditional linear dimensionality reduction methods, GANs are able to capture complex market dynamics through adversarial training, effectively reducing noise and improving prediction accuracy. The empirical analyses show that SGAN significantly outperforms existing methods in both in-sample and out-of-sample prediction capabilities. The GAN-based investment strategy achieves impressive annualized returns and provides a powerful tool for portfolio construction and risk management. Robustness tests across economic cycles, industries, and U.S. markets further validate the stability of SGAN. These findings highlight the unique advantages of GANs as sentiment-driven financial forecasting tools, providing market participants with new ways to more accurately capture sentiment-shifting trends and develop effective investment strategies.

Background The risk factors of postoperative delirium (POD), a serious while preventable complication, developed by patients undergoing knee and replacement surgery are still under investigation. In this systematic review and meta-analysis, we identified risk factors associated with POD in knee and hip replacement. Methods PubMed, Ovid MEDLINE, and Ovid EMBASE were used to identify original researches. The studies evaluating the risk factors of POD after knee and hip replacement were reviewed, and the qualities of the included studies were assessed with Newcastle–Ottawa Scale. Data were extracted, pooled, and a meta-analysis was completed Result Twenty-two studies were finally included with a total of 11934 patients who underwent knee or hip replacement and 1841 developed POD with an incidence of 17.6% (95% confidential interval (CI) 13.2–22.0%). Eighteen significant risk factors were identified including advanced age (odds ratio (OR) 1.15 95% CI 1.08–1.22), cognitive impairment (OR 6.84, 95% CI 3.27–14.33), history of cerebrovascular events (OR 2.51, 95% CI 1.28–4.91), knee replacement (OR 1.42, 95% CI 1.00–2.02), blood loss (standardized mean difference (SMD) 0.30, 95% CI 0.15–0.44), dementia (OR 3.09, 95% CI 2.10–4.56), neurologic disorders (OR 2.26, 95% CI 1.23–4.15), psychiatric illness (OR 2.74, 95% CI 1.34–5.62), and obstructive sleep apnea (OR 4.17, 95% CI 1.72–10.09) along with several comorbidity evaluation scores and laboratory markers. Conclusion We identified risk factors consistently associated with the incidence of POD in knee and hip replacement. Strategies and interventions should be implemented to the patients receiving knee or hip replacement with potential risk factors identified in this meta-analysis.

Objectives To identify predictors of length of stay (LOS) after total hip arthroplasty (THA) in an enhanced recovery after surgery (ERAS) program and evaluate the safety and cost‐efficiency of the ERAS program with reduced LOS for unselected patients in a Chinese population. Methods A total of 311 consecutive, unselected patients undergoing primary THA at a single institution were retrospectively reviewed and divided into two groups: LOS ≤ 3 and LOS > 3 group. All patients were managed with the same ERAS protocol and went back home after discharge. Multivariate logistic regression analysis was used to determine independent risk factors for LOS > 3. Harris Hip Score at 90‐day follow‐up, 90‐day readmission rate, and hospitalization costs were compared between two groups. Results Multivariate regression analysis identified female gender (odds ratio [OR] = 2.623), living alone (OR = 4.127), and primary osteoarthritis of hip (OR = 3.565) to be correlated with LOS > 3. Preoperative hemoglobin (HB), postoperative HB, drain use, blood transfusion, diabetes, respiratory disease, osteoporosis, number of comorbidities, and CCI score showed no significant influence on LOS after adjusting for other risk factors in the multivariate model. Harris Hip Score and readmission rate at 90‐day follow‐up showed no significant differences between two groups. Patients in LOS > 3 group had approximately 3948.6 Chinese yuan higher hospital costs. Conclusion Female gender, living alone, and primary osteoarthritis of hip were identified as independent risk factors for prolonged LOS. The experience from our institution suggested aggressive management of comorbidities in the ERAS program can minimize the influence of comorbidities on LOS. The safety, efficiency, and costs‐saving benefits of the ERAS program with reduced LOS for unselected patients was confirmed in this study.