Evaluation of the impact of prospective payment systems on cholecystectomy: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to evaluate the impact of prospective payment systems (PPSs) on cholecystectomy. A comprehensive literature review was conducted, examining studies published until December 2023. The review process focused on identifying research across major databases that reported critical outcomes such as length of stay (LOS), mortality, complications, admissions, readmissions, and costs following PPS for cholecystectomy. The studies were specifically selected for their relevance to the impact of PPS or the transition from fee-for-service (FFS) to PPS. The study analyzed six papers, with three eligible for meta-analysis, to assess the impact of the shift from FFS to PPS in laparoscopic and open cholecystectomy procedures. Our findings indicated no significant changes in LOS and mortality rates following the transition from FFS to PPS. Complication rates varied and were influenced by the diagnosis-related group categorization and surgeon cost profiles under episode-based payment. There was a slight increase in admissions and readmissions, and mixed effects on hospital costs and financial margins, suggesting varied responses to PPS for cholecystectomy procedures. The impact of PPS on cholecystectomy is nuanced and varies across different aspects of healthcare delivery. Our findings indicate a need for adaptable, patient-centered PPS models that balance economic efficiency with high-quality patient care. The study emphasizes the importance of considering specific surgical procedures and patient demographics in healthcare payment reforms.

Calcium saccharate/DUSP6 suppresses renal cell carcinoma glycolytic metabolism and boosts sunitinib efficacy via the ERK-AKT pathway.

Current therapeutic options for renal cell carcinoma (RCC) are very limited, which is largely due to inadequate comprehension of molecular pathological mechanisms as well as RCC's resistance to chemotherapy. Dual-specificity phosphatase 6 (DUSP6) has been associated with numerous human diseases. However, its role in RCC is not well understood. Here, we show that diminished DUSP6 expression is linked to RCC progression and unfavorable prognosis. Mechanistically, DUSP6 serves as a tumor suppressor in RCC by intervening the TAF10 and BSCL2 via the ERK-AKT pathway. Further, DUSP6 is also transcriptionally regulated by HNF-4a. Moreover, docking experiments have indicated that DUSP6 expression is enhanced when bound by Calcium saccharate, which also inhibits RCC cell proliferation, metabolic rewiring, and sunitinib resistance. In conclusion, our study identifies Calcium saccharate as a prospective pharmacological therapeutic approach for RCC.

Effects of various living-low and training-high modes with distinct training prescriptions on sea-level performance: A network meta-analysis.

This study aimed to separately compare and rank the effect of various living-low and training-high (LLTH) modes on aerobic and anaerobic performances in athletes, focusing on training intensity, modality, and volume, through network meta-analysis. We systematically searched PubMed, Web of Science, Embase, EBSCO, and Cochrane from their inception date to June 30, 2023. Based on the hypoxic training modality and the intensity and duration of work intervals, LLTH was divided into intermittent hypoxic exposure, continuous hypoxic training, repeated sprint training in hypoxia (RSH; work interval: 5-10 s and rest interval: approximately 30 s), interval sprint training in hypoxia (ISH; work interval: 15-30 s), short-duration high-intensity interval training (s-IHT; short work interval: 1-2 min), long-duration high-intensity interval training (l-IHT; long work interval: > 5 min), and continuous and interval training under hypoxia. A meta-analysis was conducted to determine the standardized mean differences (SMDs) among the effects of various hypoxic interventions on aerobic and anaerobic performances. From 2,072 originally identified titles, 56 studies were included in the analysis. The pooled data from 53 studies showed that only l-IHT (SMDs: 0.78 [95% credible interval; CrI, 0.52-1.05]) and RSH (SMDs: 0.30 [95% CrI, 0.10-0.50]) compared with normoxic training effectively improved athletes' aerobic performance. Furthermore, the pooled data from 29 studies revealed that active intermittent hypoxic training compared with normoxic training can effectively improve anaerobic performance, with SMDs ranging from 0.97 (95% CrI, 0.12-1.81) for l-IHT to 0.32 (95% CrI, 0.05-0.59) for RSH. When adopting a program for LLTH, sufficient duration and work intensity intervals are key to achieving optimal improvements in athletes' overall performance, regardless of the potential improvement in aerobic or anaerobic performance. Nevertheless, it is essential to acknowledge that this study incorporated merely one study on the improvement of anaerobic performance by l-IHT, undermining the credibility of the results. Accordingly, more related studies are needed in the future to provide evidence-based support. It seems difficult to achieve beneficial adaptive changes in performance with intermittent passive hypoxic exposure and continuous low-intensity hypoxic training.

Midterm Outcomes of Multicenter Castor Single-Branch Stent Graft Use in the Treatment of Thoracic Aortic Diseases.

PURPOSE: The aim of this study was to evaluate the midterm efficacy and safety of a single-branch Castor stent graft in the treatment of thoracic aortic disease. MATERIALS AND METHODS: Clinical data of 106 patients with thoracic aortic disease treated with Castor single-branch stent graft at 3 centers were collected between May 2018 and June 2023. The indicators included technical success, stent-related complication, reintervention, retrograde dissection, endoleak, distal stent graft-induced entry (dSINE), branch patency, and mortality. The outcomes of the Castor stent graft for multibranch reconstruction above the arch was also analyzed. RESULTS: The technical success was 98.1% (104/106), while the surgical success was 93.4% (99/106). The reintervention was 2.8% (3/106), consisting of a case of retrograde type A dissection, an endoleak, and a dSINE. The retrograde dissection was 1.9% (2/106), while type I endoleak was 1.9% (2/106). The new dSINE was 2.8% (3/106), and the branch patency rate was 100%. The mortality was 1.9% (2/106). The mean follow-up time was 29.1±17.7 months. The 2-year post-surgery cumulative survival rate was 91.0%±3.1%, while the cumulative branch patency rate was 96.2%±2.2%. In addition, the cumulative freedom from stent-related reintervention rate was 93.2%±2.8%. A comparison showed no significant difference in the stent-related complication, branch patency, endoleak, reintervention, and mortality when the proximal end of the Castor stent graft was anchored to zones 1 or 2 of the aorta. CONCLUSION: Castor single-branch stent graft showed favorable early and midterm outcomes in the treatment of thoracic aortic disease. In addition, it was feasible to combine Castor stent graft with other advanced techniques for multibranch aortic arch reconstruction. CLINICAL IMPACT: The Castor single-branch stent graft was approval by the Chinese Food and Drug Administration in 2017. However, there were few studies on the mid-term outcomes for thoracic aortic disease after launching, which mainly focused on small single-center retrospective study. In the study, we assessed the mid-term outcomes of Castor stent graft through multi-center cases, Castor stent graft combined with other advanced techniques (such as fenestration and hybrid) for multi-branch reconstruction of aortic arch were also conducted. We found Castor single-branch stent graft showed favorable early and mid-term outcomes in the treatment of thoracic aortic disease. Additionally, it was feasible to combine Castor stent graft with other advanced technique for multi-branch aortic arch reconstruction. As an off-the-shelf branched stent graft with a wide range of models, it could be also used in most emergent situation. The Castor stent graft was expected to become more widely used in the future.

Fumarate induces LncRNA-MIR4435-2HG to regulate glutamine metabolism remodeling and promote the development of FH-deficient renal cell carcinoma.

Fumarate hydratase (FH) deficient renal cell carcinoma (RCC) is a type of tumor with definite metabolic disorder, but the mechanism of metabolic remodeling is still unclear. LncRNA was reported to closely correlate with cancer metabolism, however the biological role of LncRNA in the development of progression of FH-deficent RCC was not well studied either. FH-deficient RCC samples were collected in my hospital and used for RNA-sequencing and Mass spectrometry analysis. FH-deficient RCC cell line UOK262 and control pFH cells were used for in vitro experiments, including proliferation assay, transwell assay, western-blot, mass spectrometry and so on. PDX mouse model was used for further drug inhibition experiments in vivo. In this study, we analyzed the profiles of LncRNA and mRNA in FH-deficienct RCC samples, and we found that the LncRNA-MIR4435-2GH was specifically highly expressed in FH-deficient RCC compared with ccRCC. In vitro experiments demonstrated that MIR4435-2HG was regulated by Fumarate through histone demethylation, and the deletion of this gene could inhibit glutamine metabolism. RNA-pulldown experiments showed that MIR4435-2HG specifically binds to STAT1, which can transcriptionally activate GLS1. GLS1 inhibitor CB-839 could significantly suppress tumor growth in PDX tumor models. This study analyzed the molecular mechanism of MIR4435-2HG in regulating metabolic remodeling of FH-deficient RCC in clinical samples, cells and animal models by combining transcriptional and metabolic methods. We found that that GLS1 was a therapeutic target for this tumor, and MIR4435-2HG can be used as a drug sensitivity marker.

Comparative efficacy of concurrent training types on lower limb strength and muscular hypertrophy: A systematic review and network meta-analysis.

Objective: This study aims to compare, through quantitative analysis, the effectiveness of different endurance training types on increasing lower limb strength and muscle cross-sectional area (MCSA) in concurrent training. Methods: This systematic literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) [PROSPERO ID: CRD42023396886]. Web of Science, SportDiscuss, Pubmed, Cochrane, and Scopus were systematically searched from their inception date to October 20, 2023. Results: A total of 40 studies (841 participants) were included in this meta-analysis. MCSA analysis showed that, compared to resistance training alone, concurrent high-intensity interval running training and resistance training and concurrent moderate-intensity continuous cycling training and resistance training were more effective (SMD = 0.15, 95% CI = -0.46 to 0.76, and SMD = 0.07, 95% CI = -0.24 to 0.38 respectively), while other modalities of concurrent training not. Lower body maximal strength analysis showed that all modalities of concurrent training were inferior to resistance training alone, but concurrent high-intensity interval training and resistance training showed an advantage in four different concurrent training modalities (SMD = -0.08, 95% CI = -0.25 to 0.08). For explosive strength, only concurrent high-intensity interval training and resistance training was superior to resistance training (SMD = 0.06, 95% CI = -0.21 to 0.33). Conclusion: Different endurance training types have an impact on the effectiveness of concurrent training, particularly on lower limb strength. Adopting high-intensity interval running as the endurance training type in concurrent training can effectively minimize the adverse effects on lower limb strength and MCSA.

Extracellular vesicles related gene HSPH1 exerts anti-tumor effects in prostate cancer via promoting the stress response of CD8 + T cells.

BACKGROUND: T cell stress response state (TSTR), as a novel immune concept previous studies have proposed, has not yet been explored in prostate cancer (PC). As a type of cellular efflux, exosomes play important roles in the occurrence and development of PC. METHOD: Here, we conducted a combined analysis on extracellular vesicle related genes (EVRGs) in PC using data from single-cell RNA (scRNA), spatial transcriptome (ST), and bulk RNA sequencing. RESULT: Preliminary findings have revealed that heat shock protein family H (Hsp110) member 1 (HSPH1) possesses two identities, one being EVRGs and the other being a member of the heat shock protein family involved in TSTR, which may promote the differentiation of conventional T cells towards Th1 or Th2 cells through the pathway of IL2-MYC-IL2RA, thereby promoting the increase of CD8 + T cells in the tumor area, especially in the invasive zone, and inhibiting the invasion of PCs. We also notice the negative response of HSPH1 + CD8 + T cell related genes in immune checkpoint blockade (ICB). Western blot (WB) and droplet digital Polymerase Chain Reaction (ddPCR) demonstrated that the mRNA and protein levels of HSPH1 in EVs of PCs were significantly higher than those in adjacent tissues. CONCLUSION: Results above indicate the potential of HSPH1 as a critical therapeutic target in PC.

Involvement of TLRs/NF-κB/ESE-1 signaling pathway in T-2 toxin-induced cartilage matrix degradation.

T-2 toxin, a highly toxic type A monotrichothecene mycotoxin, has been found in many different types of cereals and is considered to be one of the most dangerous naturally occurring forms of food contamination. Globally, consuming grain-based food tainted with T-2 toxin poses significant risks to animal and human health. Prior research has indicated that the presence of T-2 toxin may lead to the demise of chondrocytes and the deterioration of the extracellular matrix of cartilage in degenerative bone and joint conditions, such as Kashin-Beck disease. However, the mechanisms by which T-2 toxin exerts its biological toxicity on the degradation of the extracellular matrix in cartilage are not well understood. In the current study, we found original results that demonstrate an upregulation of Toll-Like Receptors (TLR-2, TLR-4) and ESE-1 expression levels in the articular cartilage of a rat model subjected to T-2 toxin exposure. Furthermore, it was revealed that the exposure to T-2 toxin resulted in an increase in the expression of TLR-2, TLR-4, and ESE-1 in human C28/I2 chondrocytes. The findings of this study indicate that the increased expression of TLR-2, TLR-4, and ESE-1 may contribute to the development of degenerative osteoarthritic disease caused by T-2 toxin. Consistent with our hypotheses, we discovered that T-2 toxin increased the expression of MMP-1 and MMP-13 in human C28/I2 chondrocytes. We used a luciferase reporter gene assay to measure the activity of the ESE-1 promoter and transfected cells with plasmids encoding TLR-2 and TLR-4 to investigate their effects on this activity. TLR-2 and TLR-4 can activate ESE-1 transcriptional gene expression, and this expression is mediated through the NF-κB pathway, additional evidence is provided for the participation of the TLRs/NF-κB/ESE-1 signaling pathway in T-2 toxin-induced cartilage matrix degradation. Together, the findings indicated that the TLRs/NF-κB/ESE-1 signaling pathway played an essential part in T-2 toxin-induced cartilage matrix degradation.

Hyperhomocysteinemia may aggravate abdominal aortic aneurysm formation by up-regulating RASSF2.

Abdominal aortic aneurysm (AAA) is a fatal cardiovascular disorder with high mortality and morbidity rates. To date, no drug has shown to significantly alleviate the risk of AAA. Previous studies have indicated that hyperhomocysteinemia (HHcy) significantly increases the incidence of AAA by disrupting endothelial cell homeostasis; however, the potential molecular mechanisms require clarification. Herein, we aimed to integrate transcriptomics analysis and molecular biology experiments to explore the potential molecular targets by which HHcy may increase the incidence of AAA. We integrated two AAA data profiles (GSE57691 and GSE7084) based on previously published microarray ribonucleic acid sequencing (RNAseq) data from the GEO database. Additionally, 500 µM homocysteine-treated human aorta endothelium cells microarray dataset (GSE175748) was downloaded and processed. Subsequently, single-cell RNA-seq profiles of the aortic aneurysms (GSE155468) were downloaded, scaled, and processed for further analysis. The microarray profiles analysis demonstrated that the Ras association domain family member 2 (RASSF2) and interleukin (IL)-1ß are potentially the target genes involved in the HHcy-mediated aggravation of AAA formation. Single-cell RNAseq analysis revealed that RASSF2 might impair endothelial cell function by increasing inflammatory cell infiltration to participate in AAA formation. Finally, we conducted reverse transcription quantitative polymerase chain reaction and immunofluorescence analysis to validate the up-regulated mRNA expression of RASSF2 (p = 0.008) and IL-1ß (p = 0.002) in AAA tissue compared to control tissue. Immunofluorescence staining revealed overexpression of RASSF2 protein in AAA tissue sections compared to control tissue (p = 0.037). Co-localization of RASSF2 and the aortic endothelium cell marker, CD31, was observed in tissue sections, indicating the potential involvement of RASSF2 in aortic endothelial cells. To summarise, our preliminary study revealed that HHcy may worsen AAA formation by up-regulating the expression of RASSF2 and IL-1ß in aortic endothelium cells.

Retroperitoneoscopic Clampless, Sutureless Hybrid Therapy in the Management of Renal Hilar Tumors.

OBJECTIVE: We aimed to investigate the outcomes and feasibility of a retroperitoneoscopic clampless, sutureless hybrid technique in the management of renal hilar tumors. METHODS: A retrospective cohort of consecutive patients with renal hilar tumors who received retroperitoneoscopic clampless, sutureless hybrid therapy between January 2017 and April 2021 was included. The hybrid surgical technique involved microwave ablation (MWA), followed by clampless tumor enucleation and sutureless hemostasis. Surgical, pathological, and oncological outcomes were recorded and analyzed. RESULTS: Sixty patients were included in this study. The median tumor size was 3.5 cm (2-5), the median RENAL score was 7 (range 6-10), the median operative time was 110 min (70-130), and the median estimated blood loss was 80 mL (30-130). The median length of postoperative hospital stay was 3 days (2-4), and no warm ischemia time was observed, except in one patient who required conversion to conventional on-clamp laparoscopic partial nephrectomy (LPN) with a 10 min warm ischemia time. Three minor complications (Clavien-Dindo grade I) and one major complication (Clavien-Dindo grade III) were recorded postoperatively. Thus far, no blood transfusions have been required. Renal dysfunction or tumor recurrence did not occur within a median follow-up of 45 months. CONCLUSION: The retroperitoneoscopic hybrid technique involving MWA, clampless tumor enucleation, and sutureless hemostasis is a feasible and safe option for the management of selective renal hilar tumors. Complete tumor removal with maximal renal function preservation can be achieved, with a low complication rate.

Systematic Review and Meta-analysis of Short-term and Mid-term Outcomes After Use of t-Branch Off-the-shelf Multibranched Endograft for Elective and Urgent Treatment of Thoracoabdominal Aortic Aneurysms.

OBJECTIVE: To conduct a meta-analysis to assess the safety and efficacy of t-Branch off-the-shelf multibranched endograft for the treatment of thoracoabdominal aortic aneurysm (TAAA). DATA SOURCES: PubMed, Embase, and Web of Science. REVIEW METHODS: Online databases were searched from June 2012 to March 2023. The data were pooled together using a random-effects model of proportions. The outcomes overall included technical success, spinal cord ischemia, target vessel occlusion, type I or III endoleak, reintervention, early mortality (30-day), and mid-term outcomes. Subgroup meta-analyses and meta-regression were performed to explore variation among studies. RESULTS: A total of 15 studies containing 1238 patients were included in the meta-analysis. The overall study quality assessment was found to be moderate to good. The pooled technical success was 97.0% (95% confidence interval [CI]=95.5-98.6, I2=53.01%, 1185/1238 cases, 15 studies). Overall, early mortality was 7.3% (95% CI=4.4-10.1, I2=74.48%, 124/1238 cases, 15 studies). Early spinal cord ischemia was 13.4% (95% CI=9.6-17.2, I2=67.24%, 160/1238 cases, 15 studies), and early type I or III endoleak was 6.0% (95% CI=3.4-8.5, I2=53.71%, 68/1032 cases, 9 studies). Mid-term outcomes showed target vessel occlusion was 4% (95% CI=1.4-6.5, I2=65.18%, 28/528 cases, 10 studies, 5-21.2 months), type I or III endoleak was 4.7% (95% CI=2-7.5, I2=49.74%, 38/512 cases, 10 studies, 5-21.2 months), reintervention was 11.2% (95% CI=8.1-14.3, I2=31.06%, 85/650 cases, 10 studies, 5-21.2 months), and pooled mortality was 13.9% (95% CI=7.2-20.7, I2=76.32%, 84/550 cases, 11 studies, 5-21.2 months). Meta-regression found a significant linear association between higher technical success and earlier publication year (p=0.014) and studies with anatomic inclusion criteria (p=0.037). Urgent patients (p=0.021) and later publication year (p=0.048) were significantly associated with higher early mortality. CONCLUSION: The use of the off-the-shelf t-Branch multibranched endograft for elective or urgent endovascular TAAA repair is associated with high technical success rates and proved to be safe and effective at early and mid-term follow-up. However, the heterogeneity between the included studies is high, and prospective, randomized studies along with future larger studies with long-term follow-up are needed. CLINICAL IMPACT: The Zenith t-Branch (Cook Medical, Bloomington, Ind) was approved as a commercially available device in Europe in June 2012. Although a decade has past, the outcomes of t-Branch have rarely been synthesized at the global level. This meta-analysis included 15 studies containing 1238 patients. The meta-analyses included technical success, major adverse events, reintervention, early mortality, and mid-term outcomes. The outcome was very meaningful and representative for the use of t-Branch. It is helpful for endovascular surgeons to make decisions on the treatment of TAAA patients.

The Efficacy of Different Exercises on Mild to Moderate Adolescent Idiopathic Scoliosis: A Systematic Review and Meta-analysis.

PURPOSE: The aim of this study is to evaluate the effectiveness of different exercise interventions on patients with Adolescent Idiopathic Scoliosis (AIS) and provide evidence-based exercise prescriptions for this population. METHODS: The PubMed, Embase, The Cochrane Library, Web of Science, CNKI, Chinese Biomedical Literature Database (CBM), VIP, and Wanfang Data Knowledge Service Platform were searched until January 2023. The data were pooled and a meta-analysis was conducted. RESULTS: A total of 19 studies were conducted with 778 participants. The Schroth exercises group (MD = -3.48, 95% CI [-4.73, -2.23], P < 0.00001) and strength training group (MD = -3.43, 95% CI [-4.06, -2.80], P < 0.00001) had better recovery of the Cobb angle than the other groups. The Cobb angle rehabilitation effect was good in the time of less than 60 minutes group. Additionally, there was no significant difference found between the different intervention periods groups (P > 0.05). CONCLUSION: Schroth exercise and strength training significantly improved Cobb angle of AIS patients; Exercising for less than 60 minutes is effective for Cobb angle rehabilitation, but prolonging exercise time cannot improve training effectiveness; 12 weeks of exercise significantly improved Cobb angle, but prolonged training periods did not have a significant impact.

Midterm Results of Drug-Coated Balloon and Bare Metal Stent in the Treatment of TASCII C/D Femoropopliteal Artery Occlusive Disease: A Retrospective Multicenter Study.

PURPOSE: This study aimed to compare midterm efficacy between drug-coated balloon (DCB) and bare metal stent (BMS) in the treatment of TASCII C/D femoropopliteal artery lesions. METHODS: The clinical data of patients with TASCII C/D femoropopliteal artery disease admitted to 3 vascular surgery centers from January 2018 to January 2021 were retrospectively analyzed. Patients were divided into DCB group and BMS group. The DCB group was further subdivided into DCB alone subgroup and DCB+BMS subgroup. Study primary outcomes were freedom from clinical-driven target lesion reintervention (FCD-TLR) at 24 months postprocedure. Secondary outcomes included ankle brachial index (ABI), Rutherford classification, major amputation rate, and mortality. RESULTS: A total of 410 consecutive patients were enrolled. At 24 months follow-up, in DCB group (114 patients) relative to BMS group (296 patients), FCD-TLR (86.00% vs 71.91%, p=0.039), and ABI (0.53±0.11 vs 0.47±0.19, p=0.007) were higher; mean Rutherford class was lower (1.57±0.68 vs 3.31±1.39, p=0.000); and major amputation rate (0.87% vs 4.05%, p>0.05) and all-cause mortality (8.92% vs 6.41%, p>0.05) were statistically similar. In DCB alone, subgroup relative to DCB+BMS subgroup, FCD-TLR (90.00% vs 85.00%, p>0.05), major amputation rate (0 vs 1.08%, p>0.05), and all-cause mortality rate (9.09% vs 8.69%, p>0.05) were statistically similar, while FCD-TLR was higher in the DCB+BMS subgroup (90.00% vs 71.91%, p=0.045). CONCLUSION: At midterm follow-up of patients treated for TASCII C/D femoropopliteal artery disease, use of DCB or of DCB combined with rescue BMS appeared similarly efficacious, and yielded more favorable outcomes than use of BMS. CLINICAL IMPACT: The efficacy of drug-coated balloons relative to that of bare metal stents for the treatment of complex femoropopliteal artery lesions, particularly TASCII grade D lesions, remains uncertain. There is a scarcity of multicenter comparative studies, and in this multicenter retrospective study with up to 24-month follow-up, use of drug-coated balloon alone or combined with rescue bare metal stent appeared similarly efficacious while yielding more favorable outcomes than use of bare metal stent alone in the treatment of TASCII grade C/D femoropopliteal artery lesions. Randomized studies are warranted.

Optimal type and dose of hypoxic training for improving maximal aerobic capacity in athletes: a systematic review and Bayesian model-based network meta-analysis.

Objective: This study aimed to compare and rank the effect of hypoxic practices on maximum oxygen consumption (VO2max) in athletes and determine the hypoxic dose-response correlation using network meta-analysis. Methods: The Web of Science, PubMed, EMBASE, and EBSCO databases were systematically search for randomized controlled trials on the effect of hypoxc interventions on the VO2max of athletes published from inception until 21 February 2023. Studies that used live-high train-high (LHTH), live-high train-low (LHTL), live-high, train-high/low (HHL), intermittent hypoxic training (IHT), and intermittent hypoxic exposure (IHE) interventions were primarily included. LHTL was further defined according to the type of hypoxic environment (natural and simulated) and the altitude of the training site (low altitude and sea level). A meta-analysis was conducted to determine the standardized mean difference between the effects of various hypoxic interventions on VO2max and dose-response correlation. Furthermore, the hypoxic dosage of the different interventions were coordinated using the "kilometer hour" model. Results: From 2,072 originally identified titles, 59 studies were finally included in this study. After data pooling, LHTL, LHTH, and IHT outperformed normoxic training in improving the VO2max of athletes. According to the P-scores, LHTL combined with low altitude training was the most effective intervention for improving VO2max (natural: 0.92 and simulated: 0.86) and was better than LHTL combined with sea level training (0.56). A reasonable hypoxic dose range for LHTH (470-1,130 kmh) and HL (500-1,415 kmh) was reported with an inverted U-shaped curve relationship. Conclusion: Different types of hypoxic training compared with normoxic training serve as significant approaches for improving aerobic capacity in athletes. Regardless of the type of hypoxic training and the residential condition, LHTL with low altitude training was the most effective intervention. The characteristics of the dose-effect correlation of LHTH and LHTL may be associated with the negative effects of chronic hypoxia.

Diagnostic potential of ultrasonography and computed tomography in differentiating cervical lymph node metastasis of thyroid cancer: a systematic review and meta-analysis.

Introduction: Ultrasonography (US) and computed tomography (CT) are the most common diagnostic modalities of cervical lymph node metastasis of thyroid cancer, but few studies have been conducted to compare their diagnostic accuracy, with inconclusive results. Material and methods: Multiple databases including PubMed, Springer, EMBASE, Ovid, and the Cochrane Library were searched with the keywords "thyroid cancer OR thyroid carcinomas", "cervical lymph nodes", "metastatic OR metastasis", and "ultrasonography OR ultrasound OR CT OR computed tomography" in June 2018. Full-text articles comparing diagnostic accuracy of US and CT were reviewed. Meta-analyses were conducted to estimate sensitivity and specificity. The forest plots of sensitivity and specificity and summary receiver operating characteristic curves (SROC) are also presented in this article. Results: Finally, 8 of 1785 studies which eventually met the inclusion criteria were selected in this study. The mean sensitivities and specificities of CT in whole and central cervical areas were 0.65, 0.56 and 0.89, 0.83, respectively, while for US, the sensitivities and specificities were 0.58, 0.39 and 0.89, 0.91, respectively. The area under the curve (AUCs) observed of CT and US in whole, central and lateral cervical areas were 0.79 vs. 0.79, and 0.76 vs. 0.67. Because only a few articles were included in this study, publication bias was not assessed. Conclusions: The diagnostic accuracy of US and CT was comparable. The specificity of these two methods was much higher than the sensitivity.

Spatio-temporal heterogeneity in cancer evolution and tumor microenvironment of renal cell carcinoma with tumor thrombus.

Metastasis is the most fatal aspect of cancer, often preceded by a tumor thrombus (TT) which forms within the vascular system. Renal cell carcinoma (RCC), the predominant form of kidney cancer, witnesses a venous system invasion in 4-10% of cases, resulting in venous tumor thrombus (RCC-TT). This variant represents a formidable clinical challenge due to its escalated surgical complexity, heightened risk of progression and metastasis, and an adverse prognosis. However, recent trials addressing RCC-TT face significant barriers stemming from the profound inter- and intra-tumoral heterogeneity, patient-specific treatment variations, and distinct therapeutic resistance patterns between the primary tumor (PT) and the TT. This review delves into the unique evolutionary pathway of RCC-TT, the relationship between the staging and grading of RCC-TT invasion patterns, and the spatial molecular profiling of RCC-TT. Additionally, we assess the temporal heterogeneity among TT, PT, and distant metastases, as well as the functional phenotypes of TME components. An outlook for future research on RCC-TT is also provided.

Advances in bio-immunotherapy for castration-resistant prostate cancer.

Prostate cancer is one of the significant diseases that threaten the survival of men worldwide, with the progression of androgen deprivation therapy, become much rely on it, finally, developed into castration-resistant prostate cancer (ADT). In western countries, ranks second in incidence, and in China, with increasing lifespan, the incidence of prostate cancer is rising steadily. Although chemotherapy agents, such as taxane, have achieved some efficacy, treatment failure still occur. As sensitivity of hormone levels change, the disease can progress to castrate-resistant prostate cancer. Because of the poor efficacy of traditional surgery, endocrine therapy, radiation therapy, and chemotherapy, the treatment options for castrate-resistant prostate cancer are limited. Advanced prostate cancer can progress on immunotherapy, and thus, bio -immunotherapy targeting the unique, prostate microenvironment is an important option. In this paper, we systematically revealed the role of three types of bio-immunotherapies (immune checkpoint inhibitors, tumors, vaccines, cytokines) in castrate-resistant prostate cancer, providing a reference for clinical treatment of prostate cancer.

Serum extracellular vesicles derived hsa-miR-320d as an indicator for progression of clear cell renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is a prevalent malignancy with a rising incidence in developing countries. Clear cell renal cell carcinoma (ccRCC) constitutes 70% of RCC cases and is prone to metastasis and recurrence, yet lacks a liquid biomarker for surveillance. Extracellular vesicles (EVs) have shown promise as biomarkers in various malignancies. In this study, we investigated the potential of serum EV-derived miRNAs as a biomarker for ccRCC metastasis and recurrence. MATERIALS AND METHODS: Patients diagnosed with ccRCC between 2017 and 2020 were recruited in this study. In the discovery phase, high throughput small RNA sequencing was used to analyze RNA extracted from serum EVs derived from localized ccRCC (LccRCC) and advanced ccRCC (AccRCC). In the validation phase, qPCR was employed for quantitative detection of candidate biomarkers. Migration and invasion assays were performed on ccRCC cell line OSRC2. RESULTS: Serum EVs derived hsa-miR-320d was significantly up-regulated in patients with AccRCC than in patients with LccRCC (p < 0.01). In addition, Serum EVs derived hsa-miR-320d was also significantly up-regulated in patients who experienced recurrence or metastasis (p < 0.01). Besides, hsa-miR-320d enhances the pro-metastatic phenotype of ccRCC cells in vitro. CONCLUSIONS: Serum EVs derived hsa-miR-320d as a liquid biomarker exhibits significant potential for identifying the recurrence or metastasis of ccRCC, as well as hsa-miR-320d promotes ccRCC cells migration and invasion.

Acute hospital-community hospital care bundle for elderly orthopedic surgery patients: A propensity score-matched economic analysis.

BACKGROUND: While Singapore attains good health outcomes, Singapore's healthcare system is confronted with bed shortages and prolonged stays for elderly people recovering from surgery in acute hospitals. An Acute Hospital-Community Hospital (AH-CH) care bundle has been developed to assist patients in postoperative rehabilitation. The core concept is to transfer patients out of AHs when clinically recommended and into CHs, where they can receive more beneficial dedicated care to aid in their recovery, while freeing up bed capacities in AHs. AIM: To analyze the AH length of stay (LOS), costs, and savings associated with the AH-CH care bundle intervention initiated and implemented in elderly patients aged 75 years and above undergoing elective orthopedic surgery. METHODS: A total of 862 1:1 propensity score-matched patients aged 75 years and above who underwent elective orthopedic surgery in Singapore General Hospital (SGH) before (2017-2018) and after (2019-2021) the care bundle intervention period was analyzed. Outcome measures were AH LOS, CH LOS, hospitalization metrics, postoperative 30-d mortality, and modified Barthel Index (MBI) scores. The costs of AH inpatient hospital stay in the matched cohorts were compared using cost data in Singapore dollars. RESULTS: Of the 862 matched elderly patients undergoing elective orthopedic surgery before and after the care bundle intervention, the age distribution, sex, American Society of Anesthesiologists classification, Charlson Comorbidity Index, and surgical approach were comparable between both groups. Patients transferred to CHs after the surgery had a shorter median AH LOS (7 d vs 9 d, P < 0.001). The mean total AH inpatient cost per patient was 14.9% less for the elderly group transferred to CHs (S$24497.3 vs S$28772.8, P < 0.001). The overall AH U-turn rates for elderly patients within the care bundle were low, with a 0% mortality rate following orthopedic surgery. When elderly patients were discharged from CHs, their MBI scores increased significantly (50.9 vs 71.9, P < 0.001). CONCLUSION: The AH-CH care bundle initiated and implemented in the Department of Orthopedic Surgery appears to be effective and cost-saving for SGH. Our results indicate that transitioning care between acute and community hospitals using this care bundle effectively reduces AH LOS in elderly patients receiving orthopedic surgery. Collaboration between acute and community care providers can assist in closing the care delivery gap and enhancing service quality.