CXCL5 impedes CD8+ T cell immunity by upregulating PD-L1 expression in lung cancer via PXN/AKT signaling phosphorylation and neutrophil chemotaxis.

BACKGROUND: Lung cancer remains one of the most prevalent cancer types worldwide, with a high mortality rate. Upregulation of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) may represent a key mechanism for evading immune surveillance. Immune checkpoint blockade (ICB) antibodies against PD-1 or PD-L1 are therefore widely used to treat patients with lung cancer. However, the mechanisms by which lung cancer and neutrophils in the microenvironment sustain PD-L1 expression and impart stronger inhibition of CD8+ T cell function remain unclear. METHODS: We investigated the role and underlying mechanism by which PD-L1+ lung cancer and PD-L1+ neutrophils impede the function of CD8+ T cells through magnetic bead cell sorting, quantitative real-time polymerase chain reaction (RT-PCR), western blotting, enzyme-linked immunosorbent assays, confocal immunofluorescence, gene silencing, flow cytometry, etc. In vivo efficacy and safety studies were conducted using (Non-obeseDiabetes/severe combined immune deficiency) SCID/NOD mice. Additionally, we collected clinical and prognostic data from 208 patients who underwent curative lung cancer resection between 2017 and 2018. RESULTS: We demonstrated that C-X-C motif chemokine ligand 5 (CXCL5) is markedly overexpressed in lung cancer cells and is positively correlated with a poor prognosis in patients with lung cancer. Mechanistically, CXCL5 activates the phosphorylation of the Paxillin/AKT signaling cascade, leading to upregulation of PD-L1 expression and the formation of a positive feedback loop. Moreover, CXCL5 attracts neutrophils, compromising CD8+ T cell-dependent antitumor immunity. These PD-L1+ neutrophils aggravate CD8+ T cell exhaustion following lung cancer domestication. Combined treatment with anti-CXCL5 and anti-PD-L1 antibodies significantly inhibits tumor growth in vivo. CONCLUSIONS: Our findings collectively demonstrate that CXCL5 promotes immune escape through PD-L1 upregulation in lung cancer and neutrophils chemotaxis through autocrine and paracrine mechanisms. CXCL5 may serve as a potential therapeutic target in synergy with ICBs in lung cancer immunotherapy.

Interplay between lipid dysregulation and ferroptosis in chondrocytes and the targeted therapy effect of metformin on osteoarthritis.

INTRODUCTION: Osteoarthritis (OA) is a devastating whole-joint disease affecting a large population worldwide; the role of lipid dysregulation in OA and mechanisms underlying targeted therapy effect of lipid-lowering metformin on OA remains poorly defined. OBJECTIVES: To investigate the effects of lipid dysregulation on OA progression and to explore lipid dysregulation-targeting OA treatment of metformin. METHODS: RNA-Seq data, biochemical, and histochemical assays in human and murine OA cartilage as well as primary chondrocytes were utilized to determine lipid dysregulation. Effects of metformin, a potent lipid-lowering medication, on ACSL4 expression and chondrocyte metabolism were determined. Further molecular experiments, including RT-qPCR, western blotting, flow cytometry, and immunofluorescence staining, were performed to investigate underlying mechanisms. Mice with intra-articular injection of metformin were utilized to determine the effects on ACLT-induced OA progression. RESULTS: ACSL4 and 4-HNE expressions were elevated in human and ACLT-induced mouse OA cartilage and IL-1ß-treated chondrocytes (P < 0.05). Ferrostatin-1 largely rescued IL-1ß-induced MDA, lipid peroxidation, and ferroptotic mitochondrial morphology (P < 0.05). Metformin decreased the levels of OA-related genes (P < 0.05) and increased the levels of p-AMPK and p-ACC in IL-1ß-treated chondrocytes. Intra-articular injection of metformin alleviated ACLT-induced OA lesions in mice, and reverted the percentage of chondrocytes positive for MMP13, Col2a1, ACSL4 and 4-HNE in ACLT mice (P < 0.05). Ferroptotic chondrocytes promoted the recruitment and chemotaxis of RAW264.7 cells via CCL2, which was blocked by metformin in vitro (P < 0.05). CONCLUSION: We establish a critical role of polyunsaturated fatty acids metabolic process in OA cartilage degradation and define metformin as a potential OA treatment. Metformin reshapes lipid availability and ameliorates chondrocyte ferroptosis sensitivity via the AMPK/ACC pathway. In the future, gene-edited animals and extensive omics technologies will be utilized to reveal detailed lipids' involvement in cartilage lesions.

Deep learning in the radiologic diagnosis of osteoporosis: a literature review.

OBJECTIVE: Osteoporosis is a systemic bone disease characterized by low bone mass, damaged bone microstructure, increased bone fragility, and susceptibility to fractures. With the rapid development of artificial intelligence, a series of studies have reported deep learning applications in the screening and diagnosis of osteoporosis. The aim of this review was to summary the application of deep learning methods in the radiologic diagnosis of osteoporosis. METHODS: We conducted a two-step literature search using the PubMed and Web of Science databases. In this review, we focused on routine radiologic methods, such as X-ray, computed tomography, and magnetic resonance imaging, used to opportunistically screen for osteoporosis. RESULTS: A total of 40 studies were included in this review. These studies were divided into three categories: osteoporosis screening (n = 20), bone mineral density prediction (n = 13), and osteoporotic fracture risk prediction and detection (n = 7). CONCLUSIONS: Deep learning has demonstrated a remarkable capacity for osteoporosis screening. However, clinical commercialization of a diagnostic model for osteoporosis remains a challenge.

Extra-articular blocking technique for acetabular bone defect reconstruction.

The acetabular bone defect reconstruction is of great challenge in total hip arthroplasty (THA). Although several solutions such as autologous bone grafting, trabecular metal augment, or compromising techniques such as the medial protrusion, high inclination angle, and elevated hip center have been raised, their efficacy and reliability have not been fully substantiated. Traditional reconstruction methods may lead to bone resorption, aggravation of bone defects, unequal length of lower limbs, unbalance of hip-spine relationship, increased costs, and so on. Our team proved a new technique named extra-articular blocking to resolve this problem. The extra-articular blocking technique was a simple, economic and effective acetabular reconstructive method to resolve the massive acetabular bone defect in congenital (especially for developmental dysplasia of the hip, DDH), inflammatory, and osteolytic pathologies. This article organized as surgical technique, aims to report the surgical principle, indication, and procedure of using extra-articular blocking technique. With this technique, we have successfully solved the difficult problem of acetabular bone defect reconstruction. We found after 3 months of the surgery, there were fluoroscopic healing and remodeling. And there were no bone loss or graft absorption until the last follow-up as evidenced by radiographic observation. The survival rate of the acetabular component was 100%, no radiolucent line, changes in inclination and anteversion of the shell, as well as migration of the rotation center were identified.

Current status and future application of electrically controlled micro/nanorobots in biomedicine.

Using micro/nanorobots (MNRs) for targeted therapy within the human body is an emerging research direction in biomedical science. These nanoscale to microscale miniature robots possess specificity and precision that are lacking in most traditional treatment modalities. Currently, research on electrically controlled micro/nanorobots is still in its early stages, with researchers primarily focusing on the fabrication and manipulation of these robots to meet complex clinical demands. This review aims to compare the fabrication, powering, and locomotion of various electrically controlled micro/nanorobots, and explore their advantages, disadvantages, and potential applications.

Comparative study of trimming and resection of diseased finger superficial flexor tendons in gouty carpal tunnel syndrome.

BACKGROUND: Hyperuricemia can lead to synovial hyperplasia in the wrist. In severe cases, it can lead to the deposition of gouty stone in the carpal tunnel, resulting in increased pressure in the carpal tunnel and compression of the median nerve to cause carpal tunnel syndrome (CTS), which is called gouty carpal tunnel syndrome (GCTS). As for the surgical treatment of gouty carpal tunnel syndrome, scholars have different opinions on whether it is necessary to remove the superficial flexor tendon. The purpose of this study was to compare the clinical efficacy of trimming and resection of the diseased superficial flexor tendon in the treatment of gouty carpal tunnel syndrome. METHODS: Clinical data were collected from May 2016 to July 2021 from 10 patients (13 affected wrists) diagnosed with gouty carpal tunnel syndrome and classified into two groups according to the surgical modality: the diseased portion of the gout-eroded superficial finger tendon was trimmed in 9 wrists, and the diseased superficial finger flexor tendon was excised in 4 wrists. Values related to flexion and extension functions, 2-PD, DASH, BCTQ, VAS and recurrence in the affected fingers were compared between the two groups as well as before and after surgery in each group. RESULTS: All affected limbs used were cleared of gouty stones, finger numbness improved, no skin necrosis occurred, and all incisions healed at stage I. At follow-up (13.58 ± 5.53 months), there was no significant difference between groups in flexion and extension function, 2-PD, DASH, BCTQ, and VAS with respect to the affected fingers, and patients in both groups improved significantly before and after surgery. Treatment of only one wrist involved trimming to remove lesion-affected portions of tendon, which reappeared 1 year after surgery, and there was one case of poor recovery from greater piriformis muscle atrophy in both procedures. CONCLUSION: Regarding surgical treatment of patients with gouty carpal tunnel syndrome in which the gouty stone has invaded the superficial flexor tendons of the fingers, the diseased superficial flexor tendons can be selectively excised, and the postoperative mobility of the affected fingers may not be impaired.

[Mechanism of Gegen Qinlian Decoction in improving glucose metabolism in vitro and in vivo by alleviating hepatic endoplasmic reticulum stress].

This study investigated the mechanism of Gegen Qinlian Decoction(GQD) in improving glucose metabolism in vitro and in vivo by alleviating endoplasmic reticulum stress(ERS). Molecular docking was used to predict the binding affinity between the main effective plasma components of GQD and ERS-related targets. Liver tissue samples were obtained from normal rats, high-fat-induced diabetic rats, rats treated with metformin, and rats treated with GQD. RNA and protein were extracted. qPCR was used to measure the mRNA expression of ERS marker glucose-regulated protein 78(GRP78), and unfolded protein response(UPR) genes inositol requiring enzyme 1(Ire1), activating transcription factor 6(Atf6), Atf4, C/EBP-homologous protein(Chop), and caspase-12. Western blot was used to detect the protein expression of GRP78, IRE1, protein kinase R-like ER kinase(PERK), ATF6, X-box binding protein 1(XBP1), ATF4, CHOP, caspase-12, caspase-9, and caspase-3. The calcium ion content in liver tissues was determined by the colorimetric assay. The ERS-HepG2 cell model was established in vitro by inducing with tunicamycin for 6 hours, and 2.5%, 5%, and 10% GQD-containing serum were administered for 9 hours. The glucose oxidase method was used to measure extracellular glucose levels, flow cytometry to detect cell apoptosis, glycogen staining to measure cellular glycogen content, and immunofluorescence to detect the expression of GRP78. The intracellular calcium ion content was measured by the colorimetric assay. Whereas Western blot was used to detect GRP78 and ERS-induced IRE1, PERK, ATF6, and eukaryotic translation initiation factor 2α(eIF2α) phosphorylation. Additionally, the phosphorylation levels of insulin receptor substrate 1(IRS1), phosphatidylinositol 3-kinase regulatory subunit p85(PI3Kp85), and protein kinase B(Akt), which were involved in the insulin signaling pathway, were also measured. In addition, the phosphorylation levels of c-Jun N-terminal kinases(JNKs), which were involved in both the ERS and insulin signaling pathways, were measured by Western blot. Molecular docking results showed that GRP78, IRE1, PERK, ATF4, and various compounds such as baicalein, berberine, daidzein, jateorhizine, liquiritin, palmatine, puerarin and wogonoside had strong binding affinities, indicating that GQD might interfere with ERS-induced UPR. In vivo results showed that GQD down-regulated the mRNA transcription of Ire1, Atf6, Atf4, Grp78, caspase-12, and Chop in diabetic rats, and down-regulated GRP78, IRE1, PERK, as well as ERS-induced apoptotic factors ATF4 and CHOP, caspase-12, caspase-9, and caspase-3, while up-regulating XBP1 to enhance adaptive UPR. In addition, GQD increased the calcium ion content in liver tissues, which facilitated correct protein folding. In vitro results showed that GQD increased glucose consumption in ERS-induced HepG2 cells without significantly affecting cell viability, increased liver glycogen synthesis, down-regulated ATF6 and p-eIF2α(Ser51), and down-regulated IRE1, PERK, and GRP78, as well as p-IRS1(Ser312) and p-JNKs(Thr183/Tyr185), while up-regulating p-PI3Kp85(Tyr607) and p-Akt(Ser473). These findings suggested that GQD alleviates excessive ERS in the liver, reduces insulin resistance, and improves hepatic glucose metabolism in vivo and in vitro.

Surgical strategies and outcomes for myocardial bridges coexisting with other cardiac conditions.

BACKGROUND: Myocardial bridges are congenital coronary artery anomalies. There are still many controversies surrounding surgical treatment strategies for myocardial bridges combined with other heart disorders. The purpose of this study was to evaluate the surgical treatment strategies and outcomes in patients with these conditions. METHODS: Between March 2004 and October 2021, our institution witnessed 77 patients diagnosed with myocardial bridging who underwent surgical intervention. According to the myocardial bridge and combined heart disorder, four groups were identified: 1. isolated LAD supra-arterial myotomy group, 2. LAD CABG and(or not) myotomy  group, 3. LAD supra-arterial myotomy and grafting of other branches group, and 4. LAD supra-arterial myotomy and other cardiac surgery group. The perioperative outcomes, symptoms, life quality, mortality, and major adverse cardiac events (MACEs) were analyzed. RESULTS: There were no deaths during hospitalization and no rethoractomy for postoperative bleeding or major adverse cardiac events (MACEs). The follow-up period ranged from 2 months to 199.2 months (55.61 ± 10.21) months, the 10-year cumulative survival rates for the four groups of patients were 95.0%, 100%, 100% and 74.1%, and the 10-year freedom rates from the MACEs were 83.9%, 92.0%, 87.5% and 76.2%, respectively. CONCLUSIONS: Supra-arterial myotomy is preferred in patients with isolated myocardial bridge, and acceptable results can be achieved by choosing supra-arterial myotomy in combination with CABG or other cardiac surgery simultaneously for patients with myocardial bridges and other heart disorders.

Characterization of TCF-1 and its relationship between CD8+ TIL densities and immune checkpoints and their joint influences on prognoses of lung adenocarcinoma patients.

BACKGROUND: T cell factor-1 (TCF-1) + stem-like tumor-infiltrating lymphocytes (stem-like TILs) are important memory cells in the tumor microenvironment. However, their relationship with clinicopathological features, CD8+ TIL densities, immune checkpoint inhibitors (ICs), and prognostic values remain unknown for lung adenocarcinomas (LUADs). In this study, we aimed to characterize TCF-1+ TILs and their prognostic significance in patients with surgically resected LUADs. METHODS: Expression of TCF-1, CD8, and ICs including programmed death-1 (PD-1), lymphocyte activating-3 (LAG-3), and T cell immunoglobulin and mucin-domain containing-3 (TIM-3) in TILs were estimated using immunohistochemistry of resected LUADs. The association between TCF-1 expressions and clinicopathological characteristics of patient prognoses were analyzed. RESULTS: Positive TCF-1 expression significantly correlated with advanced pathological stage, tumor grade, CD8+ TILs density, TIM-3 expression, LAG-3 expression, and PD-1 expression. TCF-1 positivity was significantly associated with a better recurrence-free survival (RFS), and overall survival (OS). Subgroup analysis revealed that the TCF-1+/CD8+ group had the best RFS and OS, while the TCF-1-/CD8- group had the worst RFS and OS. Similarly, patients with TCF-1 + PD-1- had the best prognoses and patients with TCF-1-PD-1+ had the worst prognoses. CONCLUSION: TCF-1 had relatively high positive expression and special clinicopathological features in patients with LUAD. TCF-1+ TILs were related to CD8 density, TIM-3 expression, LAG-3 expression, and PD-1 expression, and were associated with better prognoses in LUAD patients. A combination of TCF-1 and CD8 densities or PD-1 expression further stratified patients into different groups with distinct prognoses.

Adipokines regulate mesenchymal stem cell osteogenic differentiation.

Mesenchymal stem cells (MSCs) can differentiate into various tissue cell types including bone, adipose, cartilage, and muscle. Among those, osteogenic differentiation of MSCs has been widely explored in many bone tissue engineering studies. Moreover, the conditions and methods of inducing osteogenic differentiation of MSCs are continuously advancing. Recently, with the gradual recognition of adipokines, the research on their involvement in different pathophysiological processes of the body is also deepening including lipid metabolism, inflammation, immune regulation, energy disorders, and bone homeostasis. At the same time, the role of adipokines in the osteogenic differentiation of MSCs has been gradually described more completely. Therefore, this paper reviewed the evidence of the role of adipokines in the osteogenic differentiation of MSCs, emphasizing bone formation and bone regeneration.

Sustained and Targeted Delivery of Self-Assembled Doxorubicin Nonapeptides Using pH-Responsive Hydrogels for Osteosarcoma Chemotherapy.

While chemotherapeutic agents have particularly potent effects in many types of cancer, their clinical applications are still far from satisfactory due to off-target drug exposure, chemotherapy resistance, and adverse effects, especially in osteosarcoma. Therefore, it is clinically promising to construct a novel tumor-targeted drug delivery system to control drug release and alleviate side effects. In this study, a pH-responsive nonapeptide hydrogel was designed and fabricated for the tumor-targeted drug delivery of doxorubicin (DOX). Using a solid-phase synthesis method, a nonapeptide named P1 peptide that is structurally akin to surfactant-like peptides (SLPs) due to its hydrophobic tail and hydrophilic head was synthesized. The physicochemical properties of the P1 hydrogel were characterized via encapsulation capacity, transmission electron microscopy (TEM), circular dichroism (CD), zeta potential, rheological analysis, and drug release studies. We also used in vitro and in vivo experiments to investigate the cytocompatibility and tumor inhibitory efficacy of the drug-loaded peptide hydrogel. The P1 peptide could self-assemble into biodegradable hydrogels under neutral conditions, and the prepared drug-loaded hydrogels exhibited good injectability and biocompatibility. The in vitro drug release studies showed that DOX-P1 hydrogels had high sensitivity to acidic conditions (pH 5.8 versus 7.4, up to 3.6-fold). Furthermore, the in vivo experiments demonstrated that the DOX-P1 hydrogel could not only amplify the therapeutic effect but also increase DOX accumulation at the tumor site. Our study proposes a promising approach to designing a pH-responsive hydrogel with controlled doxorubicin-release action based on self-assembled nonapeptides for targeted chemotherapy.

Isolation and characterization of extracellular vesicle-like nanoparticles derived from migrasomes.

Migrasomes comprise a recently identified unique type of extracellular vesicle (EV) containing varying numbers of small vesicles. However, the final fate of these small vesicles is still unclear. Here, we report the discovery of EV-like migrasome-derived nanoparticles (MDNPs) that are produced by migrasomes releasing internal vesicles via self-rupture and through a process similar to cell plasma membrane budding. Our results demonstrate that MDNPs have a membrane structure with a typical round-shaped morphology and have the characteristic markers of migrasomes, but do not present the markers of EVs from the cell culture supernatant. More importantly, we also show that MDNPs are loaded with a large number of microRNAs different from those found in migrasomes and EVs. Our results provide evidence that migrasomes can produce EV-like nanoparticles. These findings have important implications for understanding the unknown biological functions of migrasomes.

Extra-articular Blocking Technique to Resolve Severe Acetabular Bone Defect in Developmental Dysplasia of the Hip.

OBJECTIVE: The reconstruction of acetabular bone defect in developmental dysplasia of the hip (DDH) is a great challenge. Although several successful solutions have been raised, their efficacy and reliability have not been fully substantiated. This work aims to present a simple, economic and effective acetabular reconstructive technique to resolve the massive acetabular bone defect in DDH scenario. METHODS: This is a case series and observational study investigating the effectiveness and safety of extra-articular blocking technique in patients diagnosed as DDH of Crowe type II-III and Hartofilakidis B. Sixteen consecutive patients indicated for extra-articular blocking and treated with total hip arthroplasty were enrolled in this series from January 2019 to August 2020. The outcome measures included the surgical indicators such as acetabular coverage, prosthesis position, operational time, medical cost, and short-term follow-up indicators such as complications profile, patient-reported functional scales, overall recovery after surgery, and radiographic bone integration and remodeling. Their medical documentation and follow-up records were carefully reviewed with ethical approval. RESULTS: The mean values of postoperative acetabular component inclination and anteversion were 42.3° ± 2.1° and 16.4° ± 1.8°, with an average acetabular coverage of 92.1%. The mean cost reduction for patients treated with this technique compared with those treated with trabecular metal augmentation was 15.3%. The mean time until walking under full-weight bearing decreased by 3.5 weeks compared with patients treated with autologous bone grafting. Within an average observational period of 18 months, the mean improvements in Harris hip score and WOMAC score were 31 and 22 points, respectively, which were identical to those with bone graft and metal augmentation techniques. No complications such as dislocation, acetabular loosening, periprosthetic joint infection, and limb length discrepancy were recorded. No signs of translucent line formation, third-party reaction, and wear-associated osteolysis were identified. CONCLUSION: The extra-articular blocking can work simply and effectively to address acetabular bone defect in DDH patients of Crowe II-III and Hartofilakidis B, as evidenced by cost-effectiveness and instant weight-bearing advantages, low failure rate, and early osteointegration and remodeling.

Comparison of lateral transperitoneal versus retroperitoneal laparoscopic adrenalectomy for pheochromocytoma: a single-centre retrospective study.

Laparoscopic adrenalectomy (LA) has became the standardized treatment for pheochromocytoma. The aim of this study was to evaluate outcomes of lateral transperitoneal and retroperitoneal LA for pheochromocytoma. Between January 2011 and December 2021, 142 patients with pheochromocytoma underwent LA via lateral transperitoneal (123 patients) or retroperitoneal (19 patients) approaches. Data of these patients were assessed to investigate the differences in perioperative outcomes and intraoperative haemodynamic parameters between the two procedures. Clinical parameters at presentation were comparable between the two groups, except for tumour size, which was larger in the transperitoneal group (50 [10-115] mm vs 35 [7-110] mm, P = 0.012). There were no significant differences between the two groups in terms of operation time, estimated blood loss, intraoperative transfusion rate, incidence of complications, conversion to open surgery, postoperative analgesic requirement, time to first oral intake, or mean hospital stay. Intraoperative haemodynamic parameters of the two groups were similar. After adjusting for tumour size using propensity score matching, both perioperative outcomes and haemodynamic parameters were still comparable. Lateral transperitoneal and retroperitoneal laparoscopic adrenalectomies provide similar perioperative and haemodynamic outcomes for surgical resection of pheochromocytoma.

Risk factors for hemodynamic instability during laparoscopic resection of pheochromocytoma.

BACKGROUND: Laparoscopic adrenalectomy for pheochromocytoma is associated with high risk of intraoperative hemodynamic instability. Our study aimed to identify predictive factors for hemodynamic instability during laparoscopic resection of pheochromocytoma. METHODS: Between January 2011 and December 2021, 136 patients underwent unilateral laparoscopic adrenalectomy for pheochromocytoma. The patients were divided into 2 groups depending on the presence or absence of hemodynamic instability during surgery. Intraoperative hemodynamic parameters were compared between the 2 groups. Patient demographic characteristics and preoperative evaluations were assessed for their prognostic relevance with respect to intraoperative hemodynamic instability via both univariate analysis and multivariate logistic regression analysis. RESULTS: There was greater blood pressure fluctuations and higher maximum blood pressure and heart rate in the hemodynamic instability group. More patients need intraoperative administration of vasoactive drugs in the hemodynamic instability group. In the univariate analysis, presence of coronary artery disease, tumour size, and previous hypertension history were significantly associated with intraoperative hemodynamic instability. The multivariate logistic regression analysis showed that tumour size and previous hypertension history were independent risk factors for intraoperative hemodynamic instability. CONCLUSION: Tumour size and previous hypertension history were associated with hemodynamic instability during laparoscopic resection of pheochromocytoma.

Sarcomatoid-associated gene risk index for clear cell renal cell carcinoma.

Sarcomatoid renal cell carcinoma is a de-differentiated form of kidney cancer with an extremely poor prognosis. Genes associated with sarcomatoid differentiation may be closely related to the prognosis of renal cell carcinoma. The prognosis of renal cell carcinoma itself is extremely variable, and a new prognostic model is needed to stratify patients and guide treatment. Data on clear cell renal cell carcinoma with or without sarcomatoid differentiation were obtained from TCGA database, and a sarcomatoid-associated gene risk index (SAGRI) and column line graphs were constructed using sarcomatoid-associated genes. The predictive power of the SAGRI and column line graphs was validated using an internal validation set and an independent validation set (E-MTAB-1980). The SAGRI was constructed using four sarcoma-like differentiation-related genes, COL7A1, LCTL, NPR3, ZFHX4, and had a 1-year AUC value of 0.725 in the training set, 0.712 in the internal validation set, and 0.770 in the independent validation set for TCGA training cohort, with high model reliability. The molecular characteristics among the SAGRI subgroups were analyzed by multiple methods, and results suggested that the SAGRI-HIGH subgroup may benefit more from immunotherapy to improve prognosis. SAGRI satisfactorily predicted the prognosis of patients with clear cell renal cell carcinoma with or without sarcomatoid differentiation.

Robot-assisted surgery in total knee arthroplasty: trauma maker or trauma savior? A prospective, randomized cohort study.

Background: Robotic assistance has been increasingly employed to improve the operative precision in modern knee surgery. The purpose of the study was to evaluate the trauma effect of one of the first domestically developed orthopedic surgical robots in China in a clinical trial of robot-assisted total knee arthroplasty (RA-TKA). Methods: A total of 33 patients who underwent unilateral TKA for end-stage osteoarthritis were randomized to receive RA-TKA (17 cases) or conventional manual TKA (CM-TKA) in our institution in 2020. The trauma effects of the 4 main indicators with 48 sub-indicators in terms of subsectional operative time, inflammation and coagulation markers, physical and radiographical analyses of osteotomy deviation, and postoperative comfort were analyzed. Results: Subsectional operative time analysis showed that the times for bone cutting and gap balancing with RA-TKA were 5.3 and 2.2 min shorter than those with CM-TKA (p = 0.010, p = 0.02), respectively. Arterial blood gas indicators (partial pressure of carbon dioxide, partial pressure of oxygen and SO2) 24 h after RA-TKA, as well as the white blood cell count and neutrophil ratio, were significantly lower than those after CM-TKA (p < 0.05). Inflammatory markers at 72 h after surgery showed the increments of C-reactive protein, erythrocyte sedimentation rate and D-dimer of RA-TKA declined by 180.7, 22.0 and 1050.0% (p < 0.05), respectively, referenced to the preoperative baseline values, as compared to CM-TKA. Mechanical deviation distribution exhibited percentages of region I errors for RA-TKA and CM-TKA of 76.5% and 27.1% (p = 0.000), respectively, and the success rates of one-time osteotomy were 94.1% and 62.5% (p = 0.039), respectively. Radiographical verification showed RA-TKA was more conducive to achieving mechanical alignment and ideal tibial component azimuths. Postoperative efficacy showed that patients were more comfortable after RA-TKA in terms of reduced administration of tranexamic acid, hydrocortisone and the utilization rate of temporary intensive opioid analgesics. No statistical difference in patient-reported outcome measures and complications were recorded between the two groups during continuous observation. Conclusions: Compared with CM-TKA, RA-TKA decreases rather than increases trauma. It might shorten the time required for bone cutting and gap balancing, reduce mechanical errors related to the osteotomy and prosthesis position, and improve the accuracy of the mechanical alignment reconstruction. RA-TKA is also favorable in promoting postoperative comfort and minimizing inflammatory response and drug consumption. Trial registration: The Chinese Clinical Trial Registry (ChiCTR2000031282) approved registration on 26 March 2020.

Endostar Synergizes with Radiotherapy to Inhibit Angiogenesis of Cervical Cancer in a Subcutaneous Xenograft Mouse Model.

BACKGROUND: To investigate the synergic effect and underlying mechanism of Endostar, a recombinant human endostatin used for anti-angiogenesis, in radiotherapy for cervical cancer. METHODS: The Cell Counting Kit-8 (CCK-8) assay and plate cloning experiment were first employed to analyze the proliferation of HeLa and SiHa cervical cancer cells and human umbilical vein vascular endothelial cells (HUVECs). Flow cytometry was used to detect apoptosis and cell cycle progression. A tube formation assay was used to assess angiogenesis in vitro. The expression of gamma H2A histone family member X (γ-H2AX) and activation of the vascular endothelial growth factor receptor (VEGFR) signaling pathway were detected by immunofluorescence and western blotting, respectively. In a HeLa xenograft model, tumor tissue expression of CD31 and alpha smooth muscle actin and serum expression of VEGF-A were detected by immunohistochemistry (IHC) and enzyme-linked immunosorbent assay, respectively. RESULTS: The CCK-8 and plate cloning assays showed that Endostar and radiotherapy synergistically inhibited the growth of HUVECs but not HeLa and SiHa cells. The flow cytometric results showed that Endostar only promoted radiotherapy-induced apoptosis and G2/M phase arrest in HUVECs (p < 0.05). Endostar combined with radiotherapy also significantly inhibited tube formation by HUVECs (p < 0.05). Furthermore, Endostar inhibited the radiotherapy-induced expression of γH2AX (p < 0.05) and phosphorylation of VEGFR2/PI3K/AKT/DNA-PK in HUVECs (p < 0.05). IHC showed that Endostar enhanced the inhibitory effect of radiotherapy on the microvessel density in xenograft tumor tissues (p < 0.05), as well as serum VEGF-A expression (p < 0.05). The tumor volume in the combination therapy groups (1200 mm3) was significantly lower than in the control group (2500 mm3; p < 0.05). CONCLUSIONS: Our findings provide experimental evidence and a theoretical basis for the application of Endostar in combination with irradiation for anti-cervical cancer treatment.

Direct anterior approach in total hip arthroplasty: more indications and advantages than we found.

Mounting attention has been oriented to the direct anterior approach (DAA) in total hip arthroplasty (THA) because of alleged advantages in terms of tissue-sparing and minimal invasiveness, as well as fast recovery after surgery in the past decades. Doubt has also been raised by critics regarding learning curve, indications, technical feasibility, intraoperative risks and complications, and unconfirmed long-term consequences of the approach. The controversies were elaborately reviewed and discussed in a recent publication in Arthroplasty by Realyvasquez et al. from the perspective of American surgeons. This inclusive review covered the current status, technical issues, outcome evaluation, and developmental concerns of DAA in modern THA. As one of the pioneers of DAA in hip surgery communities in China, Prof. Y. Z., the corresponding author of the paper, has his own understanding and manipulation of DAA on the basis of thousands of DAA procedures he has performed. The purpose of this article was to respond to the pivotal issues discussed in the article by Realyvasquez et al., and to present our own view of points about the indications/contraindications and advantages as different from existing ideas. In particular, we proposed a Xinqiao Predictive Algorithm to quantitatively assess the indications for and feasibility of DAA for the first time. The algorithm was constructed on multiple factors derived from Chinese patients. Our study concluded that the potential advantages of DAA could be achieved by personalizing the pelvic functional position and placing the component into the real safe zone, by means of adapting to the spaciotemporal change of the hip-spine coordination.

What's new in artificially intelligent joint surgery in China? The minutes of the 2021 IEEE ICRA and literature review.

OBJECTIVE: To outline the main results of the 2021 International Conference on Robotics and Automation (ICRA 2021) of the Institute of Electrical and Electronics Engineers (IEEE) and review the advances in artificially intelligent joint surgery in China. METHODS: The keynote speeches of the 2021 ICRA were summarized in detail, and publications indexed by five core electronic databases (PubMed, Cochrane, Medline, Embase and CNKI) were systematically surveyed (cutoff date: July 30, 2021) in terms of the main topics of the conference. Publications directly related to artificially intelligent joint surgery in China were identified by using the search strategies of (robotic AND arthroplasty OR replacement), (navigation AND arthroplasty OR replacement), (artificial intelligent AND arthroplasty OR replacement), and (mixed reality AND arthroplasty OR replacement) and systemically reviewed. RESULTS: While robot-assisted arthroplasty in China is mainly performed using robots made in other countries (e.g., Mako from Stryker, USA), China's domestic R&D of robots and clinical studies of robotic joint surgery have made some achievements. Although reports on the safety, effectiveness and clinical efficacy of China's domestic robot-assisted joint surgery were presented at conferences, they have rarely been published in journals. Existing data indicate that, after the learning curve is overcome, robot-assisted hip and knee replacement surgery can fully achieve the established goals of precision and individualization and can significantly improve the accuracy of prosthesis placement angle and the recovery of the mechanical axis as compared with conventional surgery. The downside is that the low level of intelligentization and individualization means that existing designs are not conducive to personalization during surgery, resulting in low cost-effectiveness. CONCLUSION: The safety and efficacy of domestic robot-assisted arthroplasty in China are well documented, and its accuracy and short-term clinical efficacy have been reported. However, the long-term clinical efficacy and the cost-effectiveness of large-scale clinical application of this technique warrants further study. The inadequacies of robot-assisted surgery should be remedied through the deep integration of medicine, engineering and the network.