Extracellular vesicles reshape the tumor microenvironment to improve cancer immunotherapy: Current knowledge and future prospects.

Tumor immunotherapy has revolutionized cancer treatment, but limitations remain, including low response rates and immune complications. Extracellular vesicles (EVs) are emerging as a new class of therapeutic agents for various diseases. Recent research shows that changes in the amount and composition of EVs can reshape the tumor microenvironment (TME), potentially improving the effectiveness of immunotherapy. This exciting discovery has sparked clinical interest in using EVs to enhance the immune system's response to cancer. In this Review, we delve into the world of EVs, exploring their origins, how they're generated, and their complex interactions within the TME. We also discuss the crucial role EVs play in reshaping the TME during tumor development. Specifically, we examine how their cargo, including molecules like PD-1 and non-coding RNA, influences the behavior of key immune cells within the TME. Additionally, we explore the current applications of EVs in various cancer therapies, the latest advancements in engineering EVs for improved immunotherapy, and the challenges faced in translating this research into clinical practice. By gaining a deeper understanding of how EVs impact the TME, we can potentially uncover new therapeutic vulnerabilities and significantly enhance the effectiveness of existing cancer immunotherapies.

Fuzheng Huayu recipe inhibits bleomycin-induced pulmonary fibrosis in rats by inhibiting M2 polarization of macrophages via the oxidative phosphorylation pathway.

Fuzheng Huayu recipe (FZHYR) is a Chinese patent medicine for the treatment of fibrosis. The effects of FZHYR on pulmonary fibrosis and macrophage polarization were investigated in vitro. FZHYR inhibited pulmonary inflammation and fibrosis and M2 polarization of macrophages in bleomycin-induced pulmonary fibrosis (BPF) of rat model. Differentially expressed genes were screened by high-throughput mRNA sequencing and GSEA showed that oxidative phosphorylation (OXPHOS) was correlated with BPF. FZHYR inhibited expressions of Ndufa2 and Ndufa6 in lung tissues of BPF rats. These findings suggest that OXPHOS pathway serves as a possible target for pulmonary fibrosis therapy by FZHYR.

Giant Intrauterine Mass Because of Puerperal Infection: A Case Report.

Background: Puerperal infection is one of the four main causes of maternal mortality. A giant intrauterine mass caused by puerperal infection is a rare form of infection. The delay in treatment may result in the removal of the uterus. Case Presentation: We report a case of a large intrauterine mass resulting from puerperal infection, in which the uterus was salvaged through antibiotic treatment and curettage. The patient was a 27-year-old female, who presented with a large intrauterine mass, accompanied by fever and abdominal pain 35 days after vaginal delivery. The large intrauterine mass was ultimately pathologically confirmed to be necrotic smooth muscle tissue instead of residual pregnancy tissue. Conclusion: In most cases, the intrauterine mass after pregnancy is residual pregnancy tissue. Early identification and management are critical to ensure a good prognosis for patients. Obstetricians and pregnant women should be fully aware of the hazards of puerperal infections.

Enhancing clinical decision-making: A novel nomogram for stratifying cancer-specific survival in middle-aged individuals with follicular thyroid carcinoma utilizing SEER data.

Background: Thyroid cancer (TC) is the most common malignant tumor in the endocrine system, is also one of the head and neck tumor. Follicular Thyroid Carcinoma (FTC) plays an important role in the pathological classification of thyroid cancer. This study aimed to develop an innovative predictive tool, a nomogram, for predicting cancer specific survival (CSS) in middle-aged FTC patients. Methods: We collected patient data from the Surveillance, Epidemiology, and End Results (SEER) database. The data from patients between 2004 and 2015 were used as the training set, and the data from patients between 2016 and 2018 were used as the validation set. To identify independent risk factors affecting patient survival, univariate and multivariate Cox regression analyses were performed. Based on this, we developed a nomogram model aimed at predicting CSS in middle-aged patients with FTC. The consistency index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), and the calibration curve were used to evaluate the accuracy and confidence of the model. Results: A total of 2470 patients were enrolled in this study, in which patients from 2004 to 2015 were randomly assigned to the training cohort (N = 1437) and validation cohort (N = 598), and patients from 2016 to 2018 were assigned to the external validation cohort (N = 435) in terms of time. Univariate and multivariate Cox regression analysis showed that marriage, histological grade and TNM stage were independent risk factors for survival. The C-index for the training cohort was 0.866 (95 % CI: 0.805-0.927), for the validation cohort it was 0.944 (95 % CI: 0.903-0.985), and for the external validation cohort, it reached 0.999 (95 % CI: 0.997-1.001). Calibration curves and AUC suggest that the model has good accuracy. Conclusions: We developed an innovative nomogram to predict CSS in middle-aged patients with FTC. Our model after a rigorous internal validation and external validation process, based on the time proved that the high level of accuracy and reliability. This tool helps healthcare professionals and patients make informed clinical decisions.

A novel nomogram to predict testicular torsion in children with acute scrotal pain: a single-center retrospective study in western China.

Background: Acute scrotal pain (ASP) is the most common urological emergency in pediatrics, and its causes include testicular torsion (TT), testicular appendage torsion, and epididymo-orchitis. Among them, TT requires prompt and accurate diagnosis and urgent surgical exploration to prevent testicular loss. Conservative anti-infective treatment is recommended for epididymo-orchitis, and surgery is considered only when scrotal abscess formation and sepsis occur. Improving the understanding of TT in primary care doctors, early diagnosis, and timely surgical exploration are essential to improve the survival rate of TT and avoid excessive treatment. This study aimed to explore the risk factors for TT in children with ASP and construct a predictive model. Methods: Clinical data of children who presented with ASP and underwent emergency scrotal exploration surgery were retrospectively analyzed, including general information, physical examination, laboratory tests, and color Doppler ultrasonography (CDU) findings. Based on surgical exploration, the outcomes were categorized as confirmed TT or not. Results: A total of 283 children were included in this study, among whom 134 had TT. The mean age of all patients was 105±47.9 months, with the majority being of Han ethnicity (87.6%) and residing in urban areas (83%). Most patients had normal C-reactive protein levels and negative results in urine routine white blood cell tests (63.3%). After conducting univariate and multivariate logistic regression analyses, we identified laterality, neutrophil count, mean erythrocyte sedimentation rate, epididymal blood flow signal, testicular parenchymal echogenicity, and testicular blood flow signal as independent risk factors influencing the occurrence of TT in ASP patients. Conclusions: This study is the report with the largest sample size on the construction of prediction models for ASP in children in southwestern China. The predictive model we developed demonstrated excellent performance and higher accuracy in predicting TT in children compared to the traditional Testicular Workup for Ischemia and Suspected Torsion (TWIST) score. It can assist pediatric surgeons in diagnosing and treating children with ASP.

Anti-PD-L1 antibody retains antitumour effects while mitigating immunotherapy-related colitis in bladder cancer-bearing mice after CT-mediated intratumoral delivery.

Drug local delivery system that directly supply anti-cancer drugs to the tumor microenvironment (TME) results in excellent tumor control and minimizes side effects associated with the anti-cancer drugs. Immune checkpoint inhibitors (ICIs) have been the mainstay of cancer immunotherapy. However, the systemic administration of ICIs is accompanied by considerable immunotherapy-related toxicity. To explore whether an anti-PD-L1 antibody administered locally via a sustained-release gel-forming carrier retains its effective anticancer function while causing fewer colitis-like side effects, CT, a previously reported depot system, was used to locally deliver an anti-PD-L1 antibody together with curcumin to the TME in bladder cancer-bearing ulcerative colitis model mice. We showed that CT-mediated intratumoral coinjection of an anti-PD-L1 antibody and curcumin enabled sustained release of both the loaded anti-PD-L1 antibody and curcumin, which contributed to substantial anticancer effects with negligible side effects on the colons of the UC model mice. However, although the anti-PD-L1 antibody administered systemically synergized with the CT-mediated intratumoral delivery of curcumin in inhibiting tumour growth, colitis was significantly worsened by intraperitoneal administration of anti-PD-L1 antibody. These findings suggested that CT is a promising agent for the local delivery of anticancer drugs, as it can allow effective anticancer functions to be retained while sharply reducing the adverse side effects associated with the systemic administration of these drugs.

Differential Bioactivation Profiles of Different GS-441524 Prodrugs in Cell and Mouse Models: ProTide Prodrugs with High Cell Permeability and Susceptibility to Cathepsin A Are More Efficient in Delivering Antiviral Active Metabolites to the Lung.

We assessed factors that determine the tissue-specific bioactivation of ProTide prodrugs by comparing the disposition and activation of remdesivir (RDV), its methylpropyl and isopropyl ester analogues (MeRDV and IsoRDV, respectively), the oral prodrug GS-621763, and the parent nucleotide GS-441524 (Nuc). RDV and MeRDV yielded more active metabolite remdesivir-triphosphate (RDV-TP) than IsoRDV, GS-621763, and Nuc in human lung cell models due to superior cell permeability and higher susceptivity to cathepsin A. Intravenous administration to mice showed that RDV and MeRDV delivered significantly more RDV-TP to the lung than other compounds. Nevertheless, all four ester prodrugs exhibited very low oral bioavailability (<2%), with Nuc being the predominant metabolite in blood. In conclusion, ProTides prodrugs, such as RDV and MeRDV, are more efficient in delivering active metabolites to the lung than Nuc, driven by high cell permeability and susceptivity to cathepsin A. Optimizing ProTides' ester structures is an effective strategy for enhancing prodrug activation in the lung.

Analysis on the location of scalp acupuncture lines based on the 2021 version of Standardized Manipulations of Acupuncture and Moxibustion--Part 2： Scalp Acupuncture. / 2021版《针灸技术操作规范（第2部分）：头针》头穴线定位疑析.

In order to better promote the popularization and application of the national standard of Standardized Manipulations of Acupuncture and Moxibustion--Part 2： Scalp Acupuncture (GB/T 21709.2-2021), and to provide reference for the improvement and formulation of the next version, in the present paper, the differences about the position descriptions of two scalp acupuncture lines Dingnie Qianxiexian (anterior oblique line of vertex-temporal, MS6) and Dingpangxian 1 (lateral line 1 of vertex, MS8) between the new (GB/T 21709.2-2021) and old (GB/T 21709.2-2008) versions of the national standards as well as the International Standard Proposal of Scalp Acupuncture Point were compared, and the disputes still existing in the 2021 version were discussed. Although the 2021 version has made relevant amendments in some controversial or non-standard contents in the 2008 version, there are still some inappropriate contents. Firstly, only the relevant revision in the attached figure 3 was mentioned in the preface, without mention of the word revision about MS6 in both English and Chinese, but actually "Chengguang" (BL6) has been changed to "Tongtian" (BL7). Secondly, The attached figure does not match the word description. There is a revision in the attached figure and text at the same time, in which the text description of Qianding (GV21) of the MS6 has not been revised, but the front Shencong (EX-HN1) in the attached figure has been changed to GV21, which is obviously inconsistent with the positioning of the MS6 according to the WHO international standard, and the basis for the revision is not known. These revisions of the 2021 version of national standard on the position of the two scalp acupoint lines in the 2008 version are inconsistent, which may make many colleagues in the acupuncture field confused. Thus, further revision is necessary.

Highly controlled synthesis of symmetrically branched tripod and pentapod nanocrystals with enhanced photocatalytic performance.

Anisotropic nanostructures with tunable optical properties induced by controllable size and symmetry have attracted much attention in many applications. Herein, we report a controlled synthesis of symmetrically branched AuCu alloyed nanocrystals. By varying Au:Cu atom ratio in precursor, Y-shaped tripods with three-fold symmetry and star-shaped pentapods with five-fold symmetry are synthesized, respectively. The growth mechanism of AuCu tripods from icosahedral seeds and AuCu pentapods from decahedral seeds is revealed. Aiming to excellent photocatalytic performance, CdS nanocrystals are controlled grown onto the sharp tips of AuCu tripods and pentapods. In addition, a carrier-selective blocking layer of Ag2S is introduced between AuCu and CdS, for achieving effective charge separation in AuCu-Ag2S-CdS nanohybrids. Through evaluating the photocatalytic performance by hydrogen generation experiments, the AuCu-Ag2S-CdS tripod nanocrystals exhibit an optimized hydrogen evolution rate of 2182 µmol·g-1·h-1. These findings will contribute greatly to the understanding of complex nanoparticle growth mechanism and provide a strategy for the design of anisotropic nanoalloys for widely photocatalytic applications.

Towards Understanding and Identification of Human Viral Co-Infections.

Viral co-infections, in which a host is infected with multiple viruses simultaneously, are common in the human population. Human viral co-infections can lead to complex interactions between the viruses and the host immune system, affecting the clinical outcome and posing challenges for treatment. Understanding the types, mechanisms, impacts, and identification methods of human viral co-infections is crucial for the prevention and control of viral diseases. In this review, we first introduce the significance of studying human viral co-infections and summarize the current research progress and gaps in this field. We then classify human viral co-infections into four types based on the pathogenic properties and species of the viruses involved. Next, we discuss the molecular mechanisms of viral co-infections, focusing on virus-virus interactions, host immune responses, and clinical manifestations. We also summarize the experimental and computational methods for the identification of viral co-infections, emphasizing the latest advances in high-throughput sequencing and bioinformatics approaches. Finally, we highlight the challenges and future directions in human viral co-infection research, aiming to provide new insights and strategies for the prevention, control, diagnosis, and treatment of viral diseases. This review provides a comprehensive overview of the current knowledge and future perspectives on human viral co-infections and underscores the need for interdisciplinary collaboration to address this complex and important topic.

Characteristics and risk factors for invasive fungal infection in hospitalized patients with acute-on-chronic hepatitis B liver failure: a retrospective cohort study from 2010 to 2023.

Background and aim: The global burden of invasive fungal infections (IFIs) is emerging in immunologic deficiency status from various disease. Patients with acute-on-chronic hepatitis B liver failure (ACHBLF) are prone to IFI and their conditions are commonly exacerbated by IFI. However, little is known about the characteristics and risk factors for IFI in hospitalized ACHBLF patients. Methods: A total of 243 hospitalized ACHBLF patients were retrospectively enrolled from January 2010 to July 2023. We performed restricted cubic spline analysis to determine the non-linear associations between independent variables and IFI. The risk factors for IFI were identified using logistic regression and the extreme gradient boosting (XGBoost) algorithm. The effect values of the risk factors were determined by the SHapley Additive exPlanations (SHAP) method. Results: There were 24 ACHBLF patients (9.84%) who developed IFI on average 17.5 (13.50, 23.00) days after admission. The serum creatinine level showed a non-linear association with the possibility of IFI. Multiple logistic regression revealed that length of hospitalization (OR = 1.05, 95% CI: 1.02-1.08, P = 0.002) and neutrophilic granulocyte percentage (OR = 1.04, 95% CI: 1.00-1.09, P = 0.042) were independent risk factors for IFI. The XGBoost algorithm showed that the use of antibiotics (SHAP value = 0.446), length of hospitalization (SHAP value = 0.406) and log (qHBV DNA) (SHAP value = 0.206) were the top three independent risk factors for IFI. Furthermore, interaction analysis revealed no multiplicative effects between the use of antibiotics and the use of glucocorticoids (P = 0.990). Conclusion: IFI is a rare complication that leads to high mortality in hospitalized ACHBLF patients, and a high neutrophilic granulocyte percentage and length of hospitalization are independent risk factors for the occurrence of IFI.

Rational Lithium Salt Molecule Tuning for Fast Charging/Discharging Lithium Metal Battery.

The electrolytes for lithium metal batteries (LMBs) are plagued by a low Li+ transference number (T+) of conventional lithium salts and inability to form a stable solid electrolyte interphase (SEI). Here, we synthesized a self-folded lithium salt, lithium 2-[2-(2-methoxy ethoxy)ethoxy]ethanesulfonyl(trifluoromethanesulfonyl) imide (LiETFSI), and comparatively studied with its structure analogue, lithium 1,1,1-trifluoro-N-[2-[2-(2-methoxyethoxy)ethoxy)]ethyl]methanesulfonamide (LiFEA). The special anion chemistry imparts the following new characteristics: i) In both LiFEA and LiETFSI, the ethylene oxide moiety efficiently captures Li+, resulting in a self-folded structure and high T+ around 0.8. ii) For LiFEA, a Li-N bond (2.069 Å) is revealed by single crystal X-ray diffraction, indicating that the FEA anion possesses a high donor number (DN) and thus an intensive interphase "self-cleaning" function for an ultra-thin and compact SEI. iii) Starting from LiFEA, an electron-withdrawing sulfone group is introduced near the N atom. The distance of Li-N is tuned from 2.069 Šin LiFEA to 4.367 Šin LiETFSI. This alteration enhances ionic separation, achieves a more balanced DN, and tunes the self-cleaning intensity for a reinforced SEI. Consequently, the fast charging/discharging capability of LMBs is progressively improved. This rationally tuned anion chemistry reshapes the interactions among Li+, anions, and solvents, presenting new prospects for advanced LMBs.

Assessment of pathogenicity and functional characterization of APPL1 gene mutations in diabetic patients.

BACKGROUND: Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) plays a crucial role in regulating insulin signaling and glucose metabolism. Mutations in the APPL1 gene have been associated with the development of maturity-onset diabetes of the young type 14 (MODY14). Currently, only two mutations [c.1655T>A (p.Leu552*) and c.281G>A p.(Asp94Asn)] have been identified in association with this disease. Given the limited understanding of MODY14, it is imperative to identify additional cases and carry out comprehensive research on MODY14 and APPL1 mutations. AIM: To assess the pathogenicity of APPL1 gene mutations in diabetic patients and to characterize the functional role of the APPL1 domain. METHODS: Patients exhibiting clinical signs and a medical history suggestive of MODY were screened for the study. Whole exome sequencing was performed on the patients as well as their family members. The pathogenicity of the identified APPL1 variants was predicted on the basis of bioinformatics analysis. In addition, the pathogenicity of the novel APPL1 variant was preliminarily evaluated through in vitro functional experiments. Finally, the impact of these variants on APPL1 protein expression and the insulin pathway were assessed, and the potential mechanism underlying the interaction between the APPL1 protein and the insulin receptor was further explored. RESULTS: A total of five novel mutations were identified, including four missense mutations (Asp632Tyr, Arg633His, Arg532Gln, and Ile642Met) and one intronic mutation (1153-16A>T). Pathogenicity prediction analysis revealed that the Arg532Gln was pathogenic across all predictions. The Asp632Tyr and Arg633His variants also had pathogenicity based on MutationTaster. In addition, multiple alignment of amino acid sequences showed that the Arg532Gln, Asp632Tyr, and Arg633His variants were conserved across different species. Moreover, in in vitro functional experiments, both the c.1894G>T (at Asp632Tyr) and c.1595G>A (at Arg532Gln) mutations were found to downregulate the expression of APPL1 on both protein and mRNA levels, indicating their pathogenic nature. Therefore, based on the patient's clinical and family history, combined with the results from bioinformatics analysis and functional experiment, the c.1894G>T (at Asp632Tyr) and c.1595G>A (at Arg532Gln) mutations were classified as pathogenic mutations. Importantly, all these mutations were located within the phosphotyrosine-binding domain of APPL1, which plays a critical role in the insulin sensitization effect. CONCLUSION: This study provided new insights into the pathogenicity of APPL1 gene mutations in diabetes and revealed a potential target for the diagnosis and treatment of the disease.

Establishment and validation of a predictive nomogram for severe pleural effusion in liver cancer patients after hepatectomy.

This study aims to develop and validate a predictive nomogram for severe postoperative pleural effusion (SPOPE) in patients undergoing hepatectomy for liver cancer. A total of 536 liver cancer patients who underwent hepatectomy at the Department of Hepatobiliary Surgery I of the Affiliated Hospital of North Sichuan Medical College from January 1, 2018, to December 31, 2022, were enrolled in a retrospective observational study and comprised the training dataset. Lasso regression and logistic regression analyses were employed to construct a predictive nomogram. The nomogram was internally validated using Bootstrapping and externally validated with a dataset of 203 patients who underwent liver cancer resection at the Department of General Surgery III of the same hospital from January 1, 2020, to December 31, 2022. We evaluated the nomogram using the receiver operating characteristic curve, calibration curve, and decision curve analysis. Variables such as drinking history, postoperative serum albumin, postoperative total bilirubin, right hepatectomy, diaphragm incision, and intraoperative blood loss were observed to be associated with SPOPE. These factors were integrated into our nomogram. The C-index of the nomogram was 0.736 (95% CI: 0.692-0.781) in the training set and 0.916 (95% CI: 0.872-0.961) in the validation set. The nomogram was then evaluated using sensitivity, specificity, positive predictive value, negative predictive value, calibration curve, and decision curve analysis. The nomogram demonstrates good discriminative ability, calibration, and clinical utility.

Brain tissue heterotopic in the adrenal gland in a child: a scarce case report.

Heterotopic brain tissue is rare and has not been reported. Our center made the first report. 4 years and 2 months old Girl presented with a cystic mass in the right adrenal gland 2 weeks after right upper abdominal pain. The operation was successful, and the diagnosis was confirmed by postoperative pathology. 6 months after the procedure, the incision healed well without recurrence. This case report has a detailed diagnosis and treatment process and satisfactory examination results. It can provide a reference for diagnosing and treating clinical HBT and reduce the risk of misdiagnosis and mistreatment.

Rosavin Alleviates LPS-Induced Acute Lung Injure by Modulating the TLR-4/NF-κB/MAPK Singnaling Pathways.

Acute lung injury (ALI) is a serious inflammatory disease with high morbidity and mortality. Rosavin is an anti-inflammatory and antioxidant phenylpropanoid and glucoside, which is isolated from Rhodiola rosea L. However, its potential molecular mechanisms and whether it has protective effects against lipopolysaccharide (LPS)-induced ALI remain to be elucidated. To assess the in vitro anti-inflammatory effects and anti-lung injury activity of rosavin, RAW264.7 and A549 cells were stimulated using 1 µg/mL LPS. Rosavin attenuated LPS-induced activation of the TLR-4/NF-κB signaling pathway in RAW264.7 cells and inhibited LPS-induced release of inflammatory factors in A549 cells. A mouse model of acute lung injury was constructed by intraperitoneal injection of 5 mg/kg LPS to observe the therapeutic effect of rosavin. Transcriptomics analysis and Western blot assays were utilized to verify the molecular mechanism, rosavin (20, 40, and 80 mg/kg) dose-dependently ameliorated histopathological alterations, reduced the levels of inflammatory factors, and inhibited the TLR-4/NF-κB/MAPK signaling pathway and apoptosis activation. Rosavin is a promising therapeutic candidate for acute lung injury by inhibiting the TLR-4/NF-κB/MAPK pathway.

Chemotherapy-Enabled Colorectal Cancer Immunotherapy of Self-Delivery Nano-PROTACs by Inhibiting Tumor Glycolysis and Avoiding Adaptive Immune Resistance.

The chemo-regulation abilities of chemotherapeutic medications are appealing to address the low immunogenicity, immunosuppressive lactate microenvironment, and adaptive immune resistance of colorectal cancer. In this work, the proteolysis targeting chimera (PROTAC) of BRD4 (dBET57) is found to downregulate colorectal cancer glycolysis through the transcription inhibition of c-Myc, which also inhibits the expression of programmed death ligand 1 (PD-L1) to reverse immune evasion and avoid adaptive immune resistance. Based on this, self-delivery nano-PROTACs (designated as DdLD NPs) are further fabricated by the self-assembly of doxorubicin (DOX) and dBET57 with the assistance of DSPE-PEG2000. DdLD NPs can improve the stability, intracellular delivery, and tumor targeting accumulation of DOX and dBET57. Meanwhile, the chemotherapeutic effect of DdLD NPs can efficiently destroy colorectal cancer cells to trigger a robust immunogenic cell death (ICD). More importantly, the chemo-regulation effects of DdLD NPs can inhibit colorectal cancer glycolysis to reduce the lactate production, and downregulate the PD-L1 expression through BRD4 degradation. Taking advantages of the chemotherapy and chemo-regulation ability, DdLD NPs systemically activated the antitumor immunity to suppress the primary and metastatic colorectal cancer progression without inducing any systemic side effects. Such self-delivery nano-PROTACs may provide a new insight for chemotherapy-enabled tumor immunotherapy.

Efficacy of the newly designed "SkyWalker" robot compared to the MAKO robotic system in primary total knee arthroplasty: a one-year follow-up study.

PURPOSE: Robot-assisted surgical systems for performing total knee arthroplasty (TKA) have gained significant attention. This study was designed to compare the surgical outcomes in primary TKA surgery between the recently developed "SkyWalker" robot system and the more commonly used MAKO robot. METHODS: A total of 75 patients undergoing primary TKA surgery by the same surgical team were included in this study, with 30 patients in the "SkyWalker" group and 45 patients in the "MAKO" group. We documented the osteotomy plan for both robotic systems. The lower limb alignment angles were evaluated by postoperative radiographic assessment. The operation time, estimated blood loss, postoperative hospital stays, and changes in laboratory indexes were collected during hospitalization. In addition, a comparative evaluation of knee functional assessments and complications was conducted during six month and one year follow-ups. RESULTS: There were no significant differences between the two groups in terms of the accuracy of restoring lower limb alignment, estimated blood loss, or operation time. The knee function assessments at six months and one year postoperatively were similar in both groups. Except for day three after surgery, the level of interleukin-6 (IL-6) and the change in IL-6 (∆IL-6) from preoperative baseline were higher in the "SkyWalker" group than in the MAKO group (median: 20.53 vs. 14.17, P=0.050 and median: 17.30 vs. 10.09, P=0.042, respectively). Additionally, one patient from the MAKO group underwent revision surgery at nine months postoperatively due to ongoing periprosthetic discomfort. CONCLUSIONS: The newly developed "SkyWalker" robot showed comparable efficacy to the MAKO robot in terms of lower limb alignment accuracy and postoperative six month and one year follow-up of clinically assessed resumption of knee function.

Regulatory effect of physiological tensile stress on differentiation of ATDC5 chondrocytes through Nell-1/Ihh signaling pathway / 吉林大学学报(医学版)

Objective:To discuss the regulatory effect of physiological tensile stress on the differentiation of chondrocytes,and to clarify the associated signaling pathway mechanism.Methods:The ATDC5 chondrocytes were cultured in vitro and subjected to physiological tensile stress by four-point bending cell mechanical loading device.Initially,the cells were divided into control group and tensile stress group(2 000 μstrain/2 h group),and further divided into different stress magnitudes(1 000,2 000,and 3 000 μstrain)for 2 h,and 2 000 μstrain for different duration time(1,2,and 4 h)groups;the cells without tensile stress were used as control group.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of type Ⅱ collagen(Col-Ⅱ),type Ⅹ collagen(Col-Ⅹ),aggregated proteoglycom(Aggrecan),sex-determining region Y-box protein 9(SOX9),vascular endothelial growth factor(VEGF),proliferating cell nuclear antigen(PCNA),Nel-like molecule tyep 1(Nell-1),Runt-related transcription factor 2(Runx2),Indian hedgehog(Ihh),patched homolog 1(Ptch-1),GLI family zinc finger protein 1(Gli-1),and hedgehog interacting protein 1(Hhip-1)mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Nell-1,Runx2,and Ihh proteins in the cells in various groups.The ATDC5 cells were divided into control group,cyclopamine group,tensile stress group,and cyclopamine + tensile stress group.RT-qPCR method was used to detect the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Nell-1 and Ihh proteins in the cells in various groups.Results:Compared with control group,the expression levels of Col-Ⅱ,Col-Ⅹ,Aggrecan,SOX9,VEGF,and PCNA mRNA in the cells in 2 000 μstrain/2 h group were significantly increased(P<0.01);after treated with 2 000 μstrain tensile stress for different duration time(1,2,and 4 h)or different tensile stresses(1 000,2 000,and 3 000 μstrain)for 2 h,compared with control group,the expression levels of Runx2 mRNA in the cells in other groups were increased with the prolongation of time or the increasing of tensile stress(P<0.01),and the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA were gradually increased(P<0.01),the expression levels reached the peaking at 2 000 μstrain/2 h,and then decreased but remained significantly higher than that in control group(P<0.01).The Western blotting results showed that the expression levels of Nell-1,Runx2,and Ihh proteins in the cells were consistent with the change trend of mRNA expression levels.After pre-treated with cyclopamine,compared with control group,the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine group were significantly decreased(P<0.01),and the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in tensile stress and cyclopamine+tensile stress groups were significantly increased(P<0.01);compared with cyclopamine group,the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine+tensile stress group were significantly increased(P<0.01);compared with tensile stress group,the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine + tensile stress group were significantly decreased(P<0.01).Compared with control group,the expression level of Ihh protein in the cells in cyclopamine group was significantly decreased(P<0.01),but there was no significant difference in expression level of Nell-1 protein in the cells between control group and cyclopamine group(P>0.05),while the expression levels of Nell-1 and Ihh proteins in the cells in tensile stress group and cyclopamine + tensile stress group were significantly increased(P<0.01);compared with cyclopamine group,the expression levels of Nell-1 and Ihh proteins in the cells in tensile stress group and cyclopamine + tensile stress group were significantly increased(P<0.01);compared with tensile stress group,in the expression levels of Nell-1 and Ihh proteins in the cells in cyclopamine + tensile stress group had no significant differences(P>0.05).Conclusion:After stimulated with physiological tensile stress,Nell-1 can activate the Ihh signaling pathway upstream,and regulate the differentiation of the ATDC5 chondrocytes.