T cell-redirecting antibody for treatment of solid tumors via targeting mesothelin.

T cell engaging bispecific antibodies (TCBs) have recently become significant in cancer treatment. In this study we developed MSLN490, a novel TCB designed to target mesothelin (MSLN), a glycosylphosphatidylinositol (GPI)-linked glycoprotein highly expressed in various cancers, and evaluated its efficacy against solid tumors. CDR walking and phage display techniques were used to improve affinity of the parental antibody M912, resulting in a pool of antibodies with different affinities to MSLN. From this pool, various bispecific antibodies (BsAbs) were assembled. Notably, MSLN490 with its IgG-[L]-scFv structure displayed remarkable anti-tumor activity against MSLN-expressing tumors (EC50: 0.16 pM in HT-29-hMSLN cells). Furthermore, MSLN490 remained effective even in the presence of non-membrane-anchored MSLN (soluble MSLN). Moreover, the anti-tumor activity of MSLN490 was enhanced when combined with either Atezolizumab or TAA × CD28 BsAbs. Notably, a synergistic effect was observed between MSLN490 and paclitaxel, as paclitaxel disrupted the immunosuppressive microenvironment within solid tumors, enhancing immune cells infiltration and improved anti-tumor efficacy. Overall, MSLN490 exhibits robust anti-tumor activity, resilience to soluble MSLN interference, and enhanced anti-tumor effects when combined with other therapies, offering a promising future for the treatment of a variety of solid tumors. This study provides a strong foundation for further exploration of MSLN490's clinical potential.

A novel bispecific antibody drug conjugate targeting HER2 and HER3 with potent therapeutic efficacy against breast cancer.

Antibody drug conjugate (ADC) therapy has become one of the most promising approaches in cancer immunotherapy. Bispecific targeting could enhance the efficacy and safety of ADC by improving its specificity, affinity and internalization. In this study we constructed a HER2/HER3-targeting bispecific ADC (BsADC) and characterized its physiochemical properties, target specificity and internalization in vitro, and assessed its anti-tumor activities in breast cancer cell lines and in animal models. The HER2/HER3-targeting BsADC had a drug to antibody ratio (DAR) of 2.89, displayed a high selectivity against the target JIMT-1 breast cancer cells in vitro, as well as a slightly higher level of internalization than HER2- or HER3-monospecific ADCs. More importantly, the bispecific ADC potently inhibited the viability of MCF7, JIMT-1, BT474, BxPC-3 and SKOV-3 cancer cells in vitro. In JIMT-1 breast cancer xenograft mice, a single injection of bispecific ADC (3 mg/kg, i.v.) significantly inhibited the tumor growth with an efficacy comparable to that caused by combined injection of HER2 and HER3-monospecific ADCs (3 mg/kg for each). Our study demonstrates that the bispecific ADC concept can be applied to development of more potent new cancer therapeutics than the monospecific ADCs.

Accuracy of 3.0T magnetic resonance angiography for the detection of arteriovenous fistula dysfunction in hemodialysis patients requiring interventional therapy: a prospective study.

Background: Color Doppler ultrasonography (CDUS) is feasible to detect arteriovenous fistula (AVF) dysfunction in hemodialysis patients but is not sufficient to map the structure of fistula required for interventions. This study is designed to evaluate the diagnostic accuracy of three-dimensional time-of-flight magnetic resonance angiography (TOF-MRA) at 3.0T versus CDUS for AVF dysfunction, by using digital subtraction angiography (DSA) as reference. Methods: This prospective study enrolled 68 consecutive patients with dysfunctional AVF who underwent both CDUS and TOF-MRA at Shanghai Sixth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine. The analysis of the dysfunctional AVFs was divided into three regions: the feeding artery, fistula and draining veins. In the whole- and per-regional-based analyses, two observers who were blinded to the clinical and DSA results independently analyzed all CDUS and TOF-MRA datasets. The image quality and stenosis severity of the lesions on TOF-MRA were evaluated. A receiver operating characteristic curve was applied to analyze the detection of AVF dysfunction with TOF-MRA. Results: A total of 204 vessel regions were evaluated. The whole-region-based image quality of TOF-MRA was poorer in patients with a total occlusion (1.8±0.8) than in those with stenosis (2.7±0.6, P<0.001). In the whole-region analyses, TOF-MRA had higher sensitivity [99.1% (94.6-100.0%) vs. 82.9% (74.6-89.0%), P<0.001] and similar specificity [93.1% (85.0-97.1%) vs. 94.3% (86.5-97.9%), P=0.755] than CDUS. The per-region-based analyses showed that TOF-MRA yielded higher sensitivity [fistula region, 98.1% (88.4-99.9%) vs. 80.8% (67.0-89.9%); P=0.004; draining vein region, 100.0% (92.5-100.0%) vs. 85.0% (72.9-2.5%); P=0.003] and similar specificity [fistula region, 88.2% (62.3-97.8%) vs. 88.2% (62.3-97.9%); P>0.99; draining vein region, 100.0% (59.8-100.0%) vs. 87.5% (46.7-99.3%); P>0.99] than CDUS. Sensitivity and specificity of TOF-MRA were comparable to those of CDUS in feeding artery region. Conclusions: TOF-MRA is a feasible and accurate method to display AVF dysfunction in hemodialysis patients, and this method might fulfill the endovascular treatment planning requirements.

SQSTM1/p62 is a prognostic molecular marker and potential therapeutic target for pancreatic neuroendocrine tumours.

BACKGROUND: There have been few studies on the role of autophagy in pancreatic neuroendocrine tumours (PNETs). SQSTM1/p62 (also called Sequestosome 1) is a potential autophagy regulator, and its biological roles and clinical significance in PNETs remain poorly understood. PURPOSE: The purpose of this study was to evaluate the clinical significance of SQSTM1/p62 in human PNET specimens and to evaluate its potential value as a therapeutic target by studying its biological function in PNET cell lines. METHODS: SQSTM1/p62 protein expression was assessed in 106 PNET patient specimens by immunohistochemistry, and the relationship between SQSTM1/p62 protein expression and the clinicopathological features of PNETs in patients was analysed. The proliferation, invasion and apoptosis of SQSTM1/p62-knockdown QGP-1 and INS-1 cells were assessed by the MTT assay, a Transwell assay and flow cytometry. Cell autophagy was assessed by western blotting and mCherry-GFP-LC3B. RESULTS: The protein expression of SQSTM1/p62 in PNET patient specimens was significantly correlated with tumour recurrence (p = 0.005) and worse prognosis (log rank p = 0.020). Downregulation of the SQSTM1/p62 gene inhibited tumour cell proliferation and migration and induced PNET cell death. Downregulation of SQSTM1/p62 activated autophagy in PNET cell lines but blocked autophagic flow. Knockdown of the SQSTM1/p62 gene inhibited mTOR phosphorylation. CONCLUSION: The SQSTM1/P62 protein could be an independent prognostic marker for PNET patients. Downregulating SQSTM1/P62 can inhibit PNET progression, inhibit mTOR phosphorylation and block autophagic flow.

Circ0060467 sponges miR-6805 to promote hepatocellular carcinoma progression through regulating AIFM2 and GPX4 expression.

BACKGROUND: Circular RNAs (circRNAs) represent a subset of non-coding RNAs implicated in the regulation of diverse biological processes, including tumorigenesis. However, the expression and functional implications of circ0060467 in hepatocellular carcinoma (HCC) remain elusive. In this study, we aimed to elucidate the role of circ0060467 in modulating the progression of HCC. METHODS: Differentially expressed circRNAs in HCC tissues were identified through circRNA microarray assays. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays revealed the upregulation of circ0060467 in both HCC cell lines and tissues. Various assays were conducted to investigate the roles of circ0060467 in HCC progression. Additionally, RNA immunoprecipitation (RIP) assays and luciferase assays were carried out to assess the interactions between circ0060467, microRNA-6085 (miR-6085), apoptosis-inducing factor mitochondria-associated 2 (AIFM2), and glutathione peroxidase 4 (GPX4) in HCC. RESULTS: Microarray and qRT-PCR analyses demonstrated a marked elevation of circ0060467 in HCC tissues and cell lines. Knockdown of circ0060467 suppressed HCC cell proliferation. Luciferase reporter and RIP assays confirmed the binding of circ0060467, AIFM2, and GPX4 to miR-6805. Subsequent experiments revealed that circ0060467 competes with AIFM2 and GPX4, thereby inhibiting cancer cell ferroptosis by binding to miR-6085 and promoting hepatocellular carcinoma progression. CONCLUSIONS: Collectively, circ0060467 modulates the levels of AIFM2 and GPX4, crucial regulators of tumor cell ferroptosis, by acting as a sponge for miR-6085 in HCC. Thus, circ0060467 may represent a novel diagnostic marker and therapeutic target for HCC.

Natural products modulate NLRP3 in ulcerative colitis.

Ulcerative colitis (UC) is a clinically common, progressive, devastating, chronic inflammatory disease of the intestine that is recurrent and difficult to treat. Nod-like receptor protein 3 (NLRP3) is a protein complex composed of multiple proteins whose formation activates cysteine aspartate protease-1 (caspase-1) to induce the maturation and secretion of inflammatory mediators such as interleukin (IL)-1ß and IL-18, promoting the development of inflammatory responses. Recent studies have shown that NLRP3 is associated with UC susceptibility, and that it maintains a stable intestinal environment by responding to a wide range of pathogenic microorganisms. The mainstay of treatment for UC is to control inflammation and relieve symptoms. Despite a certain curative effect, there are problems such as easy recurrence after drug withdrawal and many side effects associated with long-term medication. NLRP3 serves as a core link in the inflammatory response. If the relationship between NLRP3 and gut microbes and inflammation-associated factors can be analyzed concerning its related inflammatory signaling pathways, its expression status as well as specific mechanism in the course of IBD can be elucidated and further considered for clinical diagnosis and treatment of IBD, it is expected that the development of lead compounds targeting the NLRP3 inflammasome can be developed for the treatment of IBD. Research into the prevention and treatment of UC, which has become a hotbed of research in recent years, has shown that natural products are rich in therapeutic means, and multi-targets, with fewer adverse effects. Natural products have shown promise in treating UC in numerous basic and clinical trials over the past few years. This paper describes the regulatory role of the NLRP3 inflammasome in UC and the mechanism of recent natural products targeting NLRP3 against UC, which provides a reference for the clinical treatment of this disease.

Design and synthesis of isatin derivatives as effective SARS-CoV-2 3CL protease inhibitors.

SARS-CoV-2 chymotrypsin-like cysteine protease (3CLpro ) is one of the most widely developed drug targets for COVID-19. This study aimed to design and synthesize isatin derivatives to target SARS-CoV-2 3CLpro in a covalent binding manner. Through the process, a potent 3CLpro inhibitor (5g) was discovered with an IC50 value of 0.43 ± 0.17 µM. To understand the binding affinity and specificity of 5g as a candidate inhibitor of SARS-CoV-2 3CLpro , several assays were conducted, including FRET enzyme activity assays, thermodynamic-based and kinetic-based validation of inhibitor-target interactions, and cell-based FlipGFP assays. The interaction mechanism between 3CLpro -5g was characterized by docking. Overall, these findings suggest that 5g is a new potent SARS-CoV-2 3CLpro inhibitor for the treatment of COVID-19.

[Expression and Clinical Significance of Cytokines and Lymphocyte Subsets in Patients with Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To study the role of cytokines and lymphocyte subsets in the diagnosis, prognosis and efficacy evaluation of DLBCL patients, and the effects of Tislelizumab on immune function and cytokines in DLBCL patients. METHODS: Twenty-three patients with newly diagnosed DLBCL were selected as DLBCL group and 34 patients with megaloblastic anemia as the control group. The levels of peripheral blood cytokines IL-2, IL-4, IL-6, IL-10, TNF- α and IFN-γ by ELISA method. The levels of peripheral blood CD3+, CD4+, CD8+ T lymphocytes, B lymphocytes and NK cells， the ratio of CD4+/CD8+ were detected by flow cytometry. The levels of cytokins and lymphocyto subsets in DLBCL patients with different clinical data and different therapeutic effects were compared. RESULTS: The levels of cytokines IL-2, IL-6 and IL-10 in DLBCL group were significantly higher than those in control group, but there was no significant correlation between cytokine levels and age and gender. The higher IPI score, higher Ann Arbor stage, B symptoms, higher ß 2-MG, LDH and CRP levels, IL-6 and IL-10 levels were significantly higher, and IL-4 was also significantly higher in patients with high LDH levels. Compared with the ineffective group, the levels of IL-6 and IL-10 were significantly lower and the level of CD4+ T cells and the ratio of CD4+/CD8+ was significantly higher in the effective group before therapy. The levels of IL-6, IL-10 and B lymphocytes in the effective group decreased significantly after therapy compared to those before therapy. After 4 cycles of therapy, the level of IL-2 and the ratio of CD4+/CD8+ in the Tislelizumab group were significantly higher than those in the non-Tislelizumab group, and the level of CD8+ T cells was significantly lower than that in the non-Tislelizumab group(P<0.05). The level of B lymphocytes in both the Tislelizumab group and the non-Tislelizumab group after therapy was significantly lower than that before therapy. CONCLUSION: The expression of cytokines and lymphocyte subsets in peripheral blood of patients with DLBCL is abnormal, which is related to the severity, prognosis and therapeutic effect of the disease. Tislelizumab can improve the immune function of patients with DLBCL by affecting cytokines and lymphocyte subsets and strengthen anti-tumor immunity.

Coexistence of diffuse large B-cell lymphoma, acute myeloid leukemia, and untreated lymphoplasmacytic lymphoma/waldenström macroglobulinemia in a same patient: A case report.

BACKGROUND: The Coexistence of myeloid and lymphoid malignancies is rare. Myeloid leukemia occurs more frequently as a secondary event in patients receiving chemotherapy agents for lymphoid malignancies. Synchronous diagnoses of diffuse large B-cell lymphoma (DLBCL), acute myeloid leukemia (AML), and untreated lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) in the same patient have not been reported. Here we report one such case. CASE SUMMARY: An 89-year-old man had a chest wall mass histopathologically diagnosed as DLBCL. The bone marrow and peripheral blood contained two groups of cells. One group of cells fulfilled the criteria of AML, and the other revealed the features of small B lymphocytic proliferative disorder, which we considered LPL/WM. Multiple chromosomal or genetic changes were detected in bone marrow mononuclear cells, including ATM deletion, CCND1 amplification, mutations of MYD88 (L265P) and TP53, WT1 overexpression, and fusion gene of BIRC2-ARAP1, as well as complex chromosomal abnormalities. The patient refused chemotherapy because of old age and died of pneumonia 1 mo after the final diagnosis. CONCLUSION: The coexistence of DLBCL, AML, and untreated LPL/WM in the same patient is extremely rare, which probably results from multiple steps of genetic abnormalities. Asymptomatic LPL/WM might have occurred first, then myelodysplastic syndrome-related AML developed, and finally aggressive DLBCL arose. Therefore, medical staff should pay attention to this rare phenomenon to avoid misdiagnoses.

[Multiomics and Multidimensional Testing for Efficacy Monitoring of Patients with Lymphoma].

OBJECTIVE: To explore the role of a new blood-based, multiomics and multidimensional method for evaluating the efficacy of patients with lymphoma. METHODS: 10 ml peripheral blood was extracted from each patient, and the genomic copy number aberrations (CNA) and fragment size (FS) were evaluated by low-depth whole genome sequencing of cfDNA, and the level of a group of plasma tumor marker (PTM) were detected at the same time. The cancer efficacy score (CES) was obtained by standardized transformation of the value of above three numerical indexes, and the changes of CES before and after treatment were compared to evaluate the patient's response to the treatment regimen. RESULTS: A total of 35 patients' baseline data were collected, of which 23 cases (65.7%) had elevated CES values. 18 patients underwent the first time test. The results showed that the CES value of 9 patients with positive baseline CES decreased significantly at the first test, and the efficacy evaluation was PR, which was highly consistent with the imaging evaluation results of the same period. At the same time, the CNA variation spectrum of all patients were evaluated and it was found that 23 patients had partial amplification or deletion of chromosome fragments. The most common amplification site was 8q24.21, which contains important oncogenes such as MYC. The most common deletion sites were 1p36.32, 4q21.23, 6q21, 6q27, 14q32.33, and tumor suppressor-related genes such as PRDM1, ATG5, AIM1, FOXO3 and HACE1 were expressed in the above regions, so these deletions may be related to the occurrence and development of lymphoma. CONCLUSION: With the advantages of more convenience, sensitivity and non-invasive, this multiomics and multidimensional efficacy detection method can evaluate the tumor load of patients with lymphoma at the molecular level, and make more accurate efficacy evaluation, which is expected to serve the clinic better.

An Online Measurement and Calibration Method for a Radio Telescope Sub-Reflector Support Structure Using Fiber Bragg Grating.

The position and altitude of a sub-reflector have an important influence on the pointing accuracy of a radio telescope. With the increase of the antenna aperture, the stiffness of the support structure for the sub-reflector decreases. This causes deformation of the support structure when environmental loads, such as gravity, temperature, and wind load, are applied to the sub-reflector, which will seriously influence antenna pointing accuracy. This paper proposes an online measurement and calibration method for assessing the deformation of the sub-reflector support structure based on the Fiber Bragg Grating (FBG) sensors. Firstly, a reconstruction model between the strain measurements and the deformation displacements of a sub-reflector support structure is established based on the inverse finite element method (iFEM). In addition, a temperature-compensating device with an FBG sensor is designed to eliminate the effects of temperature variations on strain measurements. Considering the lack of the trained original correction, a non-uniform rational B spline (NURBS) curve is built to extend the sample data set. Next, a self-structuring fuzzy network (SSFN) is designed for calibrating the reconstruction model, which can further improve the displacement reconstruction accuracy of the support structure. Finally, a full-day experiment was carried out using a sub-reflector support model to verify the effectiveness of the proposed method.

Oligonucleotide Containing 8-Trifluoromethyl-2'-Deoxyguanosine as a Z-DNA Probe.

Z-DNA structure is a noncanonical left-handed alternative form of DNA, which has been suggested to be biologically important and is related to several genetic diseases and cancer. Therefore, investigation of Z-DNA structure associated with biological events is of great importance to understanding the functions of these molecules. Here, we described the development of a trifluoromethyl labeled deoxyguanosine derivative and employed it as a 19F NMR probe to study Z-form DNA structure in vitro and in living cells.

Two Molecular Weights Holothurian Glycosaminoglycan and Hematoporphyrin Derivative-Photodynamic Therapy Inhibit Proliferation and Promote Apoptosis of Human Lung Adenocarcinoma Cells.

Holothurian glycosaminoglycan (hGAG) is extracted from the body wall of the sea cucumber, and previous studies have shown many unique bioactivities of hGAG, including antitumor, anti-angiogenesis, anti coagulation, anti thrombosis, anti-inflammation, antidiabetic effect, antivirus, and immune regulation. The effects of 3W and 5W molecular weights hGAG with hematoporphyrin derivative-photodynamic therapy (HPD-PDT) on lung cancer were investigated. Human lung adenocarcinoma A549 cells were divided into 6 groups: control group, 3W molecular weight hGAG group, 5W molecular weight hGAG group, HPD-PDT group, 3W molecular weight hGAG + HPD-PDT group, and 5W molecular weight hGAG + HPD-PDT group. Cell morphology was observed under inverted phase contrast microscope. Cell proliferative activity was detected by CCK8 and cell apoptosis was assayed by Hoechst33258 staining and flow cytometry. The results showed that two different molecular weights hGAG could inhibit proliferation, promote apoptosis rates of A549 cells, and enhance the sensitivity of A549 cells to HPD-PDT. The combined use of hGAG and HPD-PDT has synergistic inhibitory effects on A549 cells, and the effects of 3W molecular weight hGAG are better than that of 5W molecular weight hGAG.

Unmasking BACE1 in aging and age-related diseases.

The beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) has long been considered a conventional target for Alzheimer's disease (AD). Unfortunately, AD clinical trials of most BACE1 inhibitors were discontinued due to ineffective cognitive improvement or safety challenges. Recent studies investigating the involvement of BACE1 in metabolic, vascular, and immune functions have indicated a role in aging, diabetes, hypertension, and cancer. These novel BACE1 functions have helped to identify new 'druggable' targets for BACE1 against aging comorbidities. In this review, we discuss BACE1 regulation during aging, and then provide recent insights into its enzymatic and nonenzymatic involvement in aging and age-related diseases. Our study not only proposes the perspective of BACE1's actions in various systems, but also provides new directions for using BACE1 inhibitors and modulators to delay aging and to treat age-related diseases.

Remodeling morphology of the subluxated osteotomy vertebra in closing-opening wedge osteotomy in ankylosing spondylitis: would the anterior bony beak blunt?

INTRODUCTION: To investigate the remodeling morphology of subluxated osteotomy vertebra in ankylosing spondylitis (AS) patients with thoracolumbar kyphosis after single-level closing-opening wedge osteotomy (COWO). MATERIALS AND METHODS: Standing lateral radiographs were taken to evaluate sagittal parameters including lumbar lordosis (LL), C7 sagittal vertical axis (SVA), global kyphosis (GK), sacral slope (SS), and pelvic tilt (PT). Radiographic parameters of the osteotomy vertebra included osteotomized vertebra angle (OVA), sagittal translation (ST), anterior height (AH), posterior height (PH), and middle height (MH) of the osteotomy vertebrae. Furthermore, lateral projection area of the vertebral body was also measured to evaluate the remodeling of the osteotomy vertebrae. RESULTS: Sixty AS patients who underwent single-level lumbar COWO with a minimal 2-year follow-up were included. The cohort consisted of 54 males and 6 females with an average age of 36.6 years. All patients were divided into two groups according to the development of vertebral subluxation (VS): 15 in VS group (ST ≥ 5 mm), 45 in non-VS group (ST < 5 mm). There was significant difference in the correction of GK, SVA, and the loss of correction of SVA between AS patients with and without VS. Significant difference in vertebra-related parameters regarding AH and OVA was found between VS group and non-VS group (P < 0.05). CONCLUSIONS: After COWO, new bone formation narrowing the gap and adaptive resorption of the anterior bony beak at the osteotomy level during follow-up was surprisingly favorable. However, the ability of spinal canal remodeling is limited in patients complicated with VS.

Effect of D-Limonene Nanoemulsion Edible Film on Banana (Musa sapientum Linn.) Post-Harvest Preservation.

D-limonene (4-isopropenyl-1-methylcyclohexene) is an important compound in several citrus essential oils (such as orange, lemon, tangerine, lime, and grapefruit). It has been used as a flavoring agent and as a food preservative agent, with generally recognized as safe (GRAS) status. D-limonene has been well-studied for its anti-inflammatory, antioxidant, anti-cancer, and antibacterial properties. The antibacterial activity of D-limonene against food-borne pathogens was investigated in this study by preparing a D-limonene nanoemulsion. The D-limonene solution and nanoemulsion have been prepared in six concentrations, 0.04%, 0.08%, 0.1%, 0.2%, 0.4%, and 0.8% (v/v), respectively, and the antibacterial activity was tested against four food-borne pathogens (Staphylococcus aureus, Listeria monocytogenes, Salmonella enterica, and Escherichia coli). The results showed that the D-limonene nanoemulsion had good nanoscale and overall particle size uniformity, and its particle size was about 3~5 nm. It has been found that the D-limonene solution and nanoemulsion have a minimal inhibitory concentration of 0.336 mg/mL, and that they could inhibit the growth of microorganisms efficiently. The data indicate that the D-limonene nanoemulsion has more antibacterial ability against microorganisms than the D-limonene essential oil. After bananas are treated with 1.0% and 1.5% D-limonene nanoemulsion coatings, the water loss of the bananas during storage and the percentage of weight loss are reduced, which can inhibit the activity of pectinase. The application of a biocoating provides a good degree of antibacterial activity and air and moisture barrier properties, which help with extending the shelf life of bananas.

Development of an improved diagnostic nomogram for preoperative prediction of small cell neuroendocrine cancer of the cervix.

OBJECTIVES: Accurate preoperative diagnosis of small cell neuroendocrine cancer of the cervix (SCNECC) is crucial for establishing the best treatment plan. This study aimed to develop an improved, non-invasive method for the preoperative diagnosis of SCNECC by integrating clinical, MR morphological, and apparent diffusion coefficient (ADC) information. METHODS: A total of 105 pathologically confirmed cervical cancer patients (35 SCNECC, 70 non-SCNECC) from multiple centres with complete clinical and MR records were included. Whole lesion histogram analysis of the ADC was performed. Multivariate logistic regression analysis was used to develop diagnostic models based on clinical, morphological, and histogram data. The predictive performance in terms of discrimination, calibration, and clinical usefulness of the different models was assessed. A nomogram for preoperatively discriminating SCNECC was developed from the combined model. RESULTS: In preoperative SCNECC diagnosis, the combined model, which had a diagnostic AUC (area under the curve) of 0.937 (95% CI: 0.887-0.987), outperformed the clinical-morphological model, which had an AUC of 0.869 (CI: 0.788-0.949), and the histogram model, which had an AUC of 0.872 (CI: 0.792-0.951). The calibration curve and decision curve analyses suggest that the combined model achieved good fitting and clinical utility. CONCLUSIONS: Non-invasive preoperative diagnosis of SCNECC can be achieved with high accuracy by integrating clinical, MR morphological, and ADC histogram features. The nomogram derived from the combined model can provide an easy-to-use clinical preoperative diagnostic tool for SCNECC. ADVANCES IN KNOWLEDGE: It is clear that the therapeutic strategies for SCNECC are different from those for other pathological types of cervical cancer according to V 1.2021 of the NCCN clinical practice guidelines in oncology for cervical cancer. This research developed an improved, non-invasive method for the preoperative diagnosis of SCNECC by integrating clinical, MR morphological, and apparent diffusion coefficient (ADC) information.

The Direct Anterior Approach versus the Posterolateral Approach on the Outcome of Total Hip Arthroplasty: A Retrospective Clinical Study.

OBJECTIVE: To compare the clinical results of the direct anterior approach (DAA) and posterolateral approach (PLA) in total hip arthroplasty (THA) patients. METHODS: From January 2017 to September 2019, 80 patients who received primary THA in our hospital were retrospectively selected based on the propensity score matching (PSM) method. Baseline characteristics of patients who underwent the DAA and PLA were collected. Moreover, the incision length, intraoperative blood loss, operative time, length of stay, and Harris hip score were compared between patients in the two groups. The CK level was used to assess muscle damage between patients in the DAA and PLA groups. The complications of these two approaches were also evaluated at patients' 12-month follow-up evaluation. RESULTS: There was no significant difference in baseline characteristics between patients in the two groups (p > 0.05). The patients in the DAA group had a shorter incision length (9.2 ± 0.2 vs 14.7 ± 0.5, respectively; p < 0.05) and shorter length of hospital stay (9.5 ± 0.7 vs 12.9 ± 0.8, respectively, p < 0.05) than patients in the PLA group. Moreover, the DAA was associated with a decrease in intraoperative blood loss compared with the PLA (109.1 ± 12.6 vs 305.1 ± 14.1 ml, respectively, p < 0.05). However, the operation time was longer in patients in the DAA group (130.7 ± 1.7) than in patients in the PLA group (112.6 ± 1.3 min, p < 0.05). The CK level of patients in the DAA group was lower than that of patients in the PLA group (p < 0.05). The CK level at 48 h post-surgery was negatively correlated with the Harris hip scores at 6 months after THA (r = -0.538, p = 0.000). Compared with patients in the PLA group, the muscle strength of patients in the DAA group was significantly higher than that of patients in the DAA group at 4 days (p < 0.05) and 7 days (p < 0.05) after THA. The Harris hip scores of patients in the DAA group and PLA group were 81.0 ± 0.8 vs 70.8 ± 0.7 at 6 weeks, 93.4 ± 0.9 vs 86.4 ± 0.6 at 3 months, and 96.8 ± 1.1 vs 93.4 ± 0.8 at 6 months, respectively, both p < 0.05. There was no significant difference in the incidence of complications between patients in the DAA and PLA groups (p > 0.05). CONCLUSION: DAA was superior to the PLA in improving hip function after THA. Compared with the PLA, the DAA could reduce muscle damage, which is negatively correlated with hip function. Further multi-institution studies are required with longer follow-up durations, and larger patient populations are needed to provide more definitive conclusions.

Are laparoscopic cholecystectomy and natural orifice transluminal endoscopic surgery gallbladder preserving cholecystolithotomy truly comparable? A propensity matched study.

BACKGROUND: Cholecystectomy is the preferred treatment option for symptomatic gallstones. However, another option is gallbladder-preserving cholecystolithotomy which preserves the normal physiological functions of the gallbladder in patients desiring to avoid surgical resection. AIM: To compare the feasibility, safety and effectiveness of pure natural orifice transluminal endoscopic surgery (NOTES) gallbladder-preserving cholecystolithotomy vs laparoscopic cholecystectomy (LC) for symptomatic gallstones. METHODS: We adopted propensity score matching (1:1) to compare trans-rectal NOTES cholecystolithotomy and LC patients with symptomatic gallstones. We reviewed 2511 patients with symptomatic gallstones from December 2017 to December 2020; 517 patients met the matching criteria (NOTES, 110; LC, 407), yielding 86 pairs. RESULTS: The technical success rate for the NOTES group was 98.9% vs 100% for the LC group. The median procedure time was 119 min [interquartile ranges (IQRs), 95-175] with NOTES vs 60 min (IQRs, 48-90) with LC (P < 0.001). The frequency of post-operative pain was similar between NOTES and LC: 4.7% (4/85) vs 5.8% (5/95) (P = 0.740). The median duration of post-procedure fasting with NOTES was 1 d (IQRs, 1-2) vs 2 d with LC (IQRs, 1-3) (P < 0.001). The median post-operative hospital stay for NOTES was 4 d (IQRs, 3-6) vs 4 d for LC (IQRs, 3-5), (P = 0.092). During follow-up, diarrhea was significantly less with NOTES (5.8%) compared to LC (18.6%) (P = 0.011). Gallstones and cholecystitis recurrence within a median of 12 mo (range: 6-40 mo) following NOTES was 10.5% and 3.5%, respectively. Concerns regarding the presence of abdominal wall scars were present in 17.4% (n = 15/86) of patients following LC (mainly women). CONCLUSION: NOTES provides a feasible new alternative scar-free treatment for patients who are unwilling or unable to undergo cholecystectomy. This minimally invasive organ-sparing procedure both removes the gallstones and preserves the physiological function of the gallbladder. Reducing gallstone recurrence is essential to achieving widespread clinical adoption of NOTES.