circ_WASF2 regulates ferroptosis by miR-634/ GPX4 signaling in pancreatic cancer.

PURPOSE: Pancreatic cancer (PC) is one of the most lethal malignant gastrointestinal tumors (GI) characterized by a poor prognosis. Ferroptosis is an emerging programmed cell death that plays an essential role in the progression of various cancers. Ferroptosis is driven by iron-dependent phospholipid peroxidation and is regulated by mitochondrial activity, lipid peroxidation, and reactive oxygen species (ROS). The function and mechanism of ferroptosis in PC need more research. METHODS: The levels of circRNAs, miRNAs, and mRNAs were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was used for protein detection. CCK8 assays were used to detect cell proliferation. Cell death, lipid peroxidation, ROS, and Fe2+ were detected by indicted kits. Dual-luciferase reporter and RNA pull-down assays were conducted to confirm the interaction between circRNAs, miRNAs, and mRNAs. RESULTS: In this research, we found that circular RNA hsa_circ_0000003(circ_WASF2) was upregulated in pancreatic cancer cells. The silence of circ_WASF2 inhibited cancer proliferation and increased cell death by increasing ferroptosis accompanied by up-regulation of lipid peroxidation, ROS, and Fe2+. Further studies showed that circ_WASF2 could attenuate ferroptosis by targeting miR-634 and the downstream glutathione peroxidase 4 (GPX4). GPX4 has been well-reported as a central factor in ferroptosis. Our research revealed a new pathway for regulating ferroptosis in PC. CONCLUSION: In summary, we have determined that circ_WASF2/miR-634/GPX4 contributed to ferroptosis-induced cell death, and provided a possible therapeutic target in PC.

Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer.

BACKGROUND: The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy. METHODS: HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan-Meier method was utilised to analyse progression-free survival (PFS). RESULTS: This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5-22.1) versus 9.2 months (95% CI: 7.5-13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4-18.2) versus 22.2 months (95% CI: 18.3-NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9-NA) versus 8.3 months (95% CI: 6.7-13.8)]. CONCLUSIONS: HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2. TRIAL REGISTRATION: NCT03534453. Registered at May 23, 2018.

Laparoscopic sleeve gastrectomy for premenstrual syndrome symptoms in patients with obesity.

BACKGROUND: Premenstrual syndrome (PMS) is a pathological condition characterized by a series of abnormal physical, psychological, and behavioral symptoms. We evaluated the effectiveness of laparoscopic sleeve gastrectomy (LSG) in the treatment of patients with obesity and PMS. METHODS: In this case-control study, 131 patients with obesity (BMI ≥ 27.5 kg/cm2) diagnosed with moderate-to-severe PMS from March 2018 to March 2022 were prospectively selected to undergo LSG or not at their own discretion. Participants self-reported their PMS severity using the Premenstrual Syndrome Screening Tool. Among them, 68 patients chose LSG surgery, and 63 control group patients were followed up without surgery. Data were recorded at baseline and at 3 months post-treatment. We used a multivariate analysis to assess the improvement in PMS symptoms and associated factors. RESULTS: Of the 131 patients with obesity and PMS, the improvement rate of PMS in the LSG group was 57.35% (n = 39), while the improvement rate of PMS in the control group was 25.40% (n = 16). Furthermore, our study revealed that surgery is an independent factor affecting the improvement of patients with PMS. Additionally, there was a correlation between alcohol use, T2DM and obesity-related metabolic diseases, and BMI with PMS. The changes in BMI, testosterone, and estradiol(E2) levels may also contribute to the improvement of patients with obesity and PMS. CONCLUSION: LSG can improve the management of obesity in patients with PMS to some extent. Changes in BMI, testosterone, and E2 may be indicative of improvement in patients with obesity and PMS.

Clinical Outcomes and Return to Preinjury Sports After Anatomic Reconstruction With a Gracilis Autograft Versus the Modified Broström Procedure in Patients With Generalized Joint Laxity.

Background: Generalized joint laxity (GJL) is a risk factor for inferior outcomes after the modified Broström procedure for chronic lateral ankle instability, while anatomic reconstruction with tendons is more inclined to be recommended. However, whether anatomic reconstruction could achieve better results than the modified Broström procedure in patients with GJL is unknown. Purpose: To compare clinical outcomes and return to sports between anatomic reconstruction and the modified Broström procedure in patients with GJL. Study Design: Cohort study; Level of evidence, 3. Methods: Patients with GJL (Beighton score ≥4) who underwent either the modified Broström procedure or anatomic reconstruction with gracilis autografts between 2017 and 2020 were reviewed. Included were 19 patients who underwent anatomic reconstruction (reconstruction group) and 49 patients who underwent the modified Broström procedure (MBP group). Clinical outcomes were compared using the Foot and Ankle Outcome Score (FAOS) and the Karlsson score. The rates of return to preinjury level in high-demand sports, sprain recurrence, and range of motion between the 2 groups were also compared. Results: The mean follow-up duration was 38.3 months in the reconstruction group and 43.7 months in the MBP group. The FAOS and Karlsson scores improved significantly after surgery in both groups (P < .001 for all), with the reconstruction group having significantly higher postoperative FAOS-Sports scores (87.9 ± 8.9 vs 80.5 ± 11.6; P = .015) and Karlsson scores (86.9 ± 6.1 vs 82 ± 8.4; P = .025) than the MBP group. The rate of return to preinjury high-demand sports was higher in the reconstruction group than in the MBP group (73.3% vs 38.9%; P = .034). The MBP group had a significantly higher rate of sprain recurrence (22.4% vs 0%; P = .027). More patients reported dorsiflexion restriction in the reconstruction group (n = 4; 21.1%) than in the MBP group (n = 1; 2%) (P = .019); nonetheless, there was no noticeable effect on daily life and sports. Conclusion: Better clinical outcomes, less sprain recurrence, and a higher rate of return to preinjury high-demand sports were found after anatomic reconstruction with free tendons compared with the modified Broström procedure in patients with GJL. Anatomic tendon reconstruction can be recommended for such patients, especially those participating in high-demand sports.

Multidisciplinary management based on clinical nursing pathway model for the treatment of hypertensive intracerebral hemorrhage: A randomized controlled trial.

OBJECTIVE: To explore the effectiveness of multidisciplinary management based on a clinical nursing pathway model for the treatment of hypertensive intracerebral hemorrhage (HICH). METHODS: A total of 124 patients with HICH admitted to our hospital between February 2021 and June 2023 were selected as research subjects in this randomized, controlled, unblinded study. They were divided into Control-group and Study-group using a random number table method, with 62 cases in each group. The Control-group received routine care and the Study-group adopted a multidisciplinary management approach based on the clinical nursing pathway model. A multidisciplinary intervention group including 1 attending physician, 1 psychotherapist, 1 nutritionist, 1 rehabilitation specialist, and 4 responsible nurses was constructed. From preoperative to postoperative day, patients were provided with psychological intervention, health education, respiratory tract management, and specific care for patients who were restless. One to 3 days after operation, the patients and their family members were guided in basic postoperative care and nutrition care. From the 4th day after surgery to the 1st day before discharge, patients were guided for rehabilitation exercises. Patients also received discharge advices upon discharge. Activities of daily living, neurological function, stress response indicators, incidence of complications, and nursing satisfaction before and after the intervention were compared between the 2 groups. RESULTS: After the intervention, the activities of daily living and neurological function of the 2 groups were significantly improved compared to before the intervention, and the Study-group was significantly higher than the Control-group (P < .05). After intervention, the levels of stress response indicators in both groups significantly decreased compared to before the intervention, and the Study-group was significantly lower than the Control-group (P < .05). The incidence of complications in the Study-group (3.23%) was lower than that in the Control-group (15.00%) (P < .05). Nursing satisfaction in the Study-group (95.16%) was higher than that in the Control-group (83.33%) (P < .05). CONCLUSIONS: Our findings indicate that adopting a multidisciplinary management approach based on clinical nursing pathways to intervene in patients with HICH can reduce stress response levels, reduce the risk of complications, and facilitate the recovery of neurological function and activities of daily living with high patient satisfaction.

Long-Term Protective Effects and Mechanisms of Gastric Bypass Surgery on the Kidneys in Hypertensive Obese Rat.

OBJECTIVE: Investigate the long-term protective effects of gastric bypass surgery on the kidneys of hypertensive obese rats to better understand the role of gastric bypass surgery in preventing renal injury in humans with hypertension and obesity. METHODS: Compare 6-week-old spontaneously hypertensive rats, including 30 Roux-en-Y gastric bypass (RYGB) and 30 sham operations. Body weight and blood pressure were monitored before and up to 12 months after the operation. Blood lipids, blood creatinine, and blood urea nitrogen were measured. Kidney pathology was assessed using HE staining, while renal fibrosis was observed via Masson staining. Inflammatory indicators were examined by ELISA. The expression of the NLRP3 gene in the kidney was measured using immunofluorescence and western blot, and the changes in key pathways including ASC/IL-1ß protein were verified. RESULTS: RYGB reduced the body weight of hypertensive obese rats and had a protective effect on blood pressure. Additionally, the bypass effectively mitigated renal inflammation and fibrosis. Moreover, RYGB modulated the expression of NLRP3 and prevented kidney damage via the ASC/IL-1 pathway. CONCLUSION: This study validates that RYGB effectively attains sustained blood pressure control in hypertensive obese rats and has a potential kidney-protective mechanism via the NLRP3-ASC/IL-1ß pathway.

Artificial intelligence-based models enabling accurate diagnosis of ovarian cancer using laboratory tests in China: a multicentre, retrospective cohort study.

BACKGROUND: Ovarian cancer is the most lethal gynecological malignancy. Timely diagnosis of ovarian cancer is difficult due to the lack of effective biomarkers. Laboratory tests are widely applied in clinical practice, and some have shown diagnostic and prognostic relevance to ovarian cancer. We aimed to systematically evaluate the value of routine laboratory tests on the prediction of ovarian cancer, and develop a robust and generalisable ensemble artificial intelligence (AI) model to assist in identifying patients with ovarian cancer. METHODS: In this multicentre, retrospective cohort study, we collected 98 laboratory tests and clinical features of women with or without ovarian cancer admitted to three hospitals in China during Jan 1, 2012 and April 4, 2021. A multi-criteria decision making-based classification fusion (MCF) risk prediction framework was used to make a model that combined estimations from 20 AI classification models to reach an integrated prediction tool developed for ovarian cancer diagnosis. It was evaluated on an internal validation set (3007 individuals) and two external validation sets (5641 and 2344 individuals). The primary outcome was the prediction accuracy of the model in identifying ovarian cancer. FINDINGS: Based on 52 features (51 laboratory tests and age), the MCF achieved an area under the receiver-operating characteristic curve (AUC) of 0·949 (95% CI 0·948-0·950) in the internal validation set, and AUCs of 0·882 (0·880-0·885) and 0·884 (0·882-0·887) in the two external validation sets. The model showed higher AUC and sensitivity compared with CA125 and HE4 in identifying ovarian cancer, especially in patients with early-stage ovarian cancer. The MCF also yielded acceptable prediction accuracy with the exclusion of highly ranked laboratory tests that indicate ovarian cancer, such as CA125 and other tumour markers, and outperformed state-of-the-art models in ovarian cancer prediction. The MCF was wrapped as an ovarian cancer prediction tool, and made publicly available to provide estimated probability of ovarian cancer with input laboratory test values. INTERPRETATION: The MCF model consistently achieved satisfactory performance in ovarian cancer prediction when using laboratory tests from the three validation sets. This model offers a low-cost, easily accessible, and accurate diagnostic tool for ovarian cancer. The included laboratory tests, not only CA125 which was the highest ranked laboratory test in importance of diagnostic assistance, contributed to the characterisation of patients with ovarian cancer. FUNDING: Ministry of Science and Technology of China; National Natural Science Foundation of China; Natural Science Foundation of Guangdong Province, China; and Science and Technology Project of Guangzhou, China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Application of Enhanced Recovery After Surgery in Patients with Osteoporotic Vertebral Compression Fractures Undergoing Percutaneous Kyphoplasty.

BACKGROUND: The enhanced recovery after surgery (ERAS) program helps patients recover faster and better, postoperatively. The aim of this retrospective study was to assess the clinical effectiveness of the ERAS program after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures. METHODS: We enrolled patients with osteoporotic vertebral compression fracture who had undergone PKP between January 2019 and June 2021 and divided them into the control group (CG; n = 296), without the ERAS program, and the intervention group (IG; n = 306), with the ERAS program. The visual analog scale (VAS), Oswestry Disability Index (ODI), and Barthel Index scores of the 2 groups were compared on admission and 2 days and 1, 6, and 12 months postoperatively. Perioperative evaluation parameters included the mean surgery time, length of stay (LOS), and hospitalization expenses. In addition, postoperative complications were compared. RESULTS: Regarding perioperative parameters, LOS and hospitalization expenses were significantly better in IG than in CG (P < 0.001), but the mean surgery time did not differ significantly (P > 0.05). The VAS, Barthel Index, and ODI scores were significantly better in IG than in CG at 2 days and 1 month postoperatively (P < 0.001). None of the clinical effectiveness parameters (VAS, Barthel Index, and ODI scores) differed between IG and CG at 6 or 12 months postoperatively. In addition, 141 patients in CG and 56 patients in IG experienced postoperative complications, including pressure ulcers, deep vein thrombosis, nausea and vomiting, and refracture (P = 0.970, P = 0.036, P < 0.001, P = 0.002 respectively). CONCLUSIONS: For patients undergoing PKP, the ERAS program is a reliable and effective perioperative management method that can effectively reduce LOS, postoperative pain, and economic burden and promote recovery of patients.

The Distal Fascicle of the Anterior Inferior Tibiofibular Ligament: A Potential Landmark for Lateral Ankle Ligament Reconstruction.

BACKGROUND: A reliable landmark and precise distances from the ligament attachments are needed for lateral ankle stabilization surgery. The distal fascicle of the anterior inferior tibiofibular ligament (AITFL) has been used to locate the anterior talofibular ligament (ATFL) or calcaneofibular ligament (CFL) centers on the fibula. However, there is no anatomic study to validate the distal fascicle of the AITFL as a landmark of lateral ankle ligament stabilization, and more importantly, the exact distances from the ATFL or CFL attachments to the distal fascicle of the AITFL are unknown. METHODS: Sixteen frozen cadaveric specimens (8 paired specimens) with no previous history of ankle injury were used in this study. Whether the distal fascicle of AITFL was present in each specimen was confirmed. Then, the distances from the most distal insertion of the AITFL's distal fascicle to the footprint centers of the ATFL and CFL on the fibula were measured. All measurements were performed by 2 observers, and the intraobserver and interobserver reliabilities were analyzed by intraclass correlation coefficients (ICCs). RESULTS: The distal fascicle of the AITFL was found in all specimens (100%). The mean distance from the most distal insertion of the AITFL's distal fascicle to the footprint centers of the ATFL, CFL, and the intersection center of the 2 ligaments on the fibula was 6.0 to 7.1 mm, 11.5 to 13.2 mm, and 9.0 to 10.0 mm, respectively. Excellent interobserver and intraobserver agreement (all ICCs > 0.9, P < .01) was shown in the anatomic measurements of these distances. CONCLUSION: In this cadaveric study, we found that the distal fascicle was a constant structure of the AITFL in the lateral ankle. The distances from the most distal insertion of the AITFL's distal fascicle to the ligamentous footprint centers were reliable and may be used to identify the origins of the ATFL and CFL for lateral ankle ligament reconstruction. CLINICAL RELEVANCE: This anatomic study validates the AITFL's distal fascicle as a potential landmark and, more importantly, determines the range of distances from AITFL's distal fascicle to the attachment centers of lateral ankle ligaments by anatomic measurements. The data may be used to identify the ATFL and CFL for lateral ankle stabilization surgery and become particularly valuable for endoscopic or arthroscopic techniques.

Identification of novel angiotensin converting enzyme (ACE) inhibitory peptides from Pacific saury: In vivo antihypertensive effect and transport route.

Nature food-derived angiotensin converting enzyme inhibitory peptides (ACEIPs) can be potent and safe therapeutics for many medical illnesses, particularly hypertension. In this study, novel ACEIPs were screened and identified from Pacific saury by bio-activity guided approach through ultrafiltration membrane, Sephadex G-25 and RP-HPLC. The antihypertensive effect of ultrafiltration fraction was confirmed with spontaneous hypertensive rats' (SHRs) model. The peptides sequences of which gave the best activity was identified by Q-Orbitrap-MS/MS and selectively synthesized based on the binding energy of molecular docking. Five peptides VVLASLK, LTLK, LEPWR, ELPPK and LPTEK were synthesized, and the peptide LEPWR (IC50 = 99.5 µM) showed the best ACE inhibitory ability. Furthermore, LEPWR against ACE in a mixed competitive pattern and formed six hydrogen bonds with ACE. Additionally, the apparent permeability coefficient (Papp) of LEPWR was 3.56 ± 0.14 × 10-6 cm/s and paracellular transport across tight junctions was the main pathway across the Caco-2 monolayer. Therefore, the Pacific saury is a good material to prepare ACEIPs, but antihypertensive mechanism of peptide LEPWR on SHRs needs further investigation.

Avulsion fracture is associated with more pain after anatomic repair procedure for ATFL injury at the talar side.

PURPOSE: To evaluate the clinical outcomes of anatomic repair procedure for chronic anterior talofibular ligament (ATFL) injury at the talar side, and to compare the outcomes between patients with and without concomitant avulsion fractures. It was hypothesized that anatomic repair procedure could produce similarly satisfactory outcomes for those two groups. METHODS: Thirty-nine consecutive patients with chronic ATFL injuries at the talar side who underwent anatomic repair procedure at the department of sports medicine at Peking University Third Hospital between 2013 and 2018, were retrospectively evaluated. The pain visual analogue scale (VAS), American Orthopaedic Foot & Ankle Society (AOFAS) score, Tegner score, and Foot & Ankle Outcome Score (FAOS) were recorded as the primary outcomes. Time to return to sports (RTS), surgical satisfaction, deficiency of ankle range of motion (ROM), recurrent sprain, and postoperative complications were recorded as the secondary outcomes. Outcomes were compared between patients with (Group A, 16 cases) and without (Group B, 23 cases) concomitant avulsion fractures. RESULTS: The mean follow-up time was 79.4 ± 17.0 and 76.6 ± 18.5 months for Group A and B, respectively. VAS, AOFAS, Tegner, FAOS, and all subscale scores of FAOS were significantly improved in both groups at the final follow up. Patients in group A had inferior postoperative VAS, AOFAS, FAOS, and pain score of FAOS compared to group B (1.1 ± 1.1 vs. 0.4 ± 0.5, 89.1 ± 10.1 vs. 95.2 ± 5.2, 87.2 ± 7.2 vs. 91.5 ± 4.1, and 88.4 ± 11.3 vs. 96.7 ± 3.5, respectively).The mean time to RTS, rate of satisfaction and recurrent sprain had no significant differences between group A and B (6.1 ± 2.8, 93.8%, and 18.8% vs. 5.2 ± 2.2, 100.0%, and 13.0%, respectively), and the rate of ROM deficiency was significantly higher in group A (37.5 vs. 8.7%). Avulsion fracture was identified as an independent risk factor for inferior pain score of FAOS. CONCLUSION: Anatomic repair procedure for chronic ATFL injuries at the talar side produces favourable results for patients with and without avulsion fractures at 5 to 10 years follow-up, however, avulsion fracture is associated with more pain. LEVEL OF EVIDENCE: III.

Evaluation of the Accuracy of a Polymerase Chain Reaction-Based Assay for Polymerase Epsilon Mutation Detection in Endometrial Carcinoma.

CONTEXT.­: Molecular stratification of endometrial carcinoma provides more accurate prognostic information than traditional clinicopathologic features. However, because next-generation sequencing is typically recommended for polymerase epsilon (POLE) mutation detection, the practical application of a test based on molecular stratification is limited in the clinical setting. OBJECTIVE.­: To evaluate a polymerase chain reaction (PCR)-based assay for POLE mutation detection in endometrial carcinoma. DESIGN.­: We developed a PCR-based technology called Dalton Mutation Identifier Technology (Dalton-MIT) that targets 9 mutation sites within POLE exons. Endometrial carcinoma specimens from 613 patients were tested for POLE mutations. Correlations between POLE mutations with patient clinicopathologic characteristics and prognosis were analyzed. RESULTS.­: PCR detection data showed that the incidence rate of POLE mutation was 11.4% (70 of 613). Patients with POLE mutations presented better clinicopathologic characteristics and prognosis than those with non-POLE mutations. Comparison between Dalton-MIT and next-generation sequencing in 59.5% (365 of 613) of specimens showed that the sensitivity of Dalton-MIT for detecting POLE pathogenic mutations was 100%, the specificity was 99.3%, the Youden index was .993, and the κ value was .981 (P < .001). CONCLUSIONS.­: Our data demonstrate that POLE mutation detection by Dalton-MIT correlates with next-generation sequencing. This suggests that Dalton-MIT represents a promising alternative assay for detecting POLE mutations and will facilitate the wider application of molecular stratification tools for endometrial carcinoma in the clinic.

Delta radiomics analysis for prediction of intermediary- and high-risk factors for patients with locally advanced cervical cancer receiving neoadjuvant therapy.

This study aimed to assess the feasibility of using magnetic resonance imaging (MRI)-based Delta radiomics characteristics extrapolated from the Ax LAVA + C series to identify intermediary- and high-risk factors in patients with cervical cancer undergoing surgery following neoadjuvant chemoradiotherapy. A total of 157 patients were divided into two groups: those without any intermediary- or high-risk factors and those with one intermediary-risk factor (negative group; n = 75). Those with any high-risk factor or more than one intermediary-risk factor (positive group; n = 82). Radiomics characteristics were extracted using Ax-LAVA + C MRI sequences. The data was divided into training (n = 126) and test (n = 31) sets in an 8:2 ratio. The training set data features were selected using the Mann-Whitney U test and the Least Absolute Shrinkage and Selection Operator (LASSO) test. The best radiomics features were then analyzed to build a preoperative predictive radiomics model for predicting intermediary- and high-risk factors in cervical cancer. Three models-the clinical model, the radiomics model, and the combined clinic and radiomics model-were developed in this study utilizing the random forest Algorithm. The receiver operating characteristic (ROC) curve, decision curve analysis (DCA), accuracy, sensitivity, and specificity were used to assess the predictive efficacy and clinical benefits of each model. Three models were developed in this study to predict intermediary- and high-risk variables associated with postoperative pathology for patients who underwent surgery after receiving neoadjuvant radiation. In the training and test sets, the AUC values assessed using the clinical model, radiomics model, and combined clinical and radiomics models were 0.76 and 0.70, 0.88 and 0.86, and 0.91 and 0.89, respectively. The use of machine learning algorithms to analyze Delta Ax LAVA + C MRI radiomics features can aid in the prediction of intermediary- and high-risk factors in patients with cervical cancer receiving neoadjuvant therapy.

Eosinophilic granulomatosis with polyangiitis, asthma as the first symptom, and subsequent Loeffler endocarditis: A case report.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare form of anti-neutrophil cytoplasmic antibody-associated vasculitis characterized by asthma, vasculitis, and eosinophilia. CASE SUMMARY: We report an atypical case of EGPA in a 20-year-old female patient. Unlike previously reported cases of EGPA, this patient's initial symptom was asthma associated with a respiratory infection. This was followed by Loeffler endocarditis and cardiac insufficiency. She received treatment with methylprednisolone sodium succinate, low molecular weight heparin, recombinant human brain natriuretic peptide, furosemide, cefoperazone sodium/sulbactam sodium, and acyclovir. Despite prophylactic anticoagulation, she developed a large right ventricular thrombus. EGPA diagnosis was confirmed based on ancillary test results and specialty consultations. Subsequent treatment included mycophenolate mofetil. Her overall condition improved significantly after treatment, as evidenced by decreased peripheral blood eosinophils and cardiac markers. She was discharged after 17 d. Her most recent follow-up showed normal peripheral blood eosinophil levels, restored cardiac function, and a reduced cardiac mural thrombus size. CONCLUSION: This case illustrates the swift progression of EGPA and underscores the significance of early detection and immediate intervention to ensure a favorable prognosis.

LncRNA SLC7A11-AS1 promotes the progression of hepatocellular carcinoma by mediating KLF9 ubiquitination.

Hepatocellular carcinoma (HCC) is a malignant tumor, which seriously threatens the life of patients. LncRNA SLC7A11-AS1 was reported to be abnormally expressed in HCC. Here, the functions and relative molecular regulatory mechanism of SLC7A11-AS1 in HCC were investigated. Nude mice and HCC cells were used as the experimental subjects. Knockdown or overexpression of exogenous genes was conducted in HCC cells. RT-qPCR, IHC, and western blot were employed to evaluate the abundance of genes and proteins. The malignant behaviors were evaluated using CCK-8, clone formation, wound-healing, and Transwell. The locations of SLC7A11-AS1 and KLF9 in cells were determined by FISH and IF assays. The total m6A level was evaluated by dot-blot assay. m6A modification of SLC7A11-AS1 was detected using RNA MeRIP. The interactions among molecules were validated by RIP, ChIP, dual luciferase reporter assay, and co-IP. SLC7A11-AS1 was elevated apparently in HCC cells and HCC tissues from mice. SLC7A11-AS1 silencing could suppress HCC progression, which was validated in in vivo and in vitro experiments. Furthermore, METTL3 mediated m6A modification of SLC7A11-AS1 to elevate its expression. In addition, SLC7A11-AS1 downregulated KLF9 expression by affecting STUB1-mediated ubiquitination degradation and KLF9 enhanced PHLPP2 expression to inactivate the AKT pathway. Eventually, rescue experiments revealed that KLF9 knockdown abolished SLC7A11-AS1 silencing-mediated suppression of HCC progression in vivo and in vitro. Our results unveiled that m6A-modified SLC7A11-AS1 promoted HCC progression by regulating the STUB1/KLF9/PHLPP2/AKT axis, indicating that targeting SLC7A11-AS1 might alleviate HCC progression.

Tibial Tubercle-Trochlear Groove Distance Has Better Diagnostic Reliability Than Tubercle-Posterior Cruciate Ligament Distance For Predicting Patellar Instability: A Systematic Review.

OBJECTIVE: The tibial tubercle-trochlear groove (TT-TG) distance is now routinely utilized to help determine whether a realignment procedure is necessary for patients with patellar instability. The tibial tubercle-posterior cruciate ligament (TT-PCL) distance has been explored as an alternative measurement. The aim of this study is to compare the reliability of TT-TG and TT-PCL; to explore whether there is a relationship between the TT-PCL and the TT-TG distance; to determine whether there is a relationship between the TT-TG and TT-PCL distances and knee rotation; and to compare the abilities of the TT-PCL distance and the TT-TG distance with predicted patellar instability. METHOD: This systematic review was performed in accordance with PRISMA guidelines. Three databases, PubMed, EMBASE, and Cochrane Central Register of Controlled Trials, were searched from inception to September 2021 to identify clinical studies comparing TT-TG and TT-PCL distances to patellar instability. Data on patient baseline characteristics, TT-TG and TT-PCL distances, inter-observer reliability, and area under the receiver-operating characteristic curve (AUC) were recorded. The methodological quality of the studies was assessed using the quality assessment form recommended by the Agency for Healthcare Research and Quality (AHRQ). RESULT: Twenty studies were included in the final analysis, comprising 2330 knees from 2260 patients. The current study showed that TT-TG and TT-PCL have similar observer reliability. The inter- and intra-observer reliability of TT-TG ranged from 0.807 to 0.98 and 0.553 to 0.99, respectively. The inter- and intra-observer reliability of TT-PCL ranged from 0.553 to 0.99 and 0.88 to 0.981, respectively. Six studies compared the AUC for predicting patellar instability and showed that TT-TG had better predictive performance than TT-PCL. Three studies reported a correlation between TT-TG and knee rotation, but no such relationship was found for TT-PCL. Eight studies reported a weak or moderate correlation between TT-TG and TT-PCL. CONCLUSION: TT-TG and TT-PCL have similar inter- and intra-rater reliability (as measured by ICC), but TT-TG has greater discriminatory power to predict patellar instability than TT-PCL (as measured by AUC values and odds ratio). However, considering trochlear dysplasia and individual variations, future studies need to find more accurate and individualized methods to predict patellar instability.

The Significance of Human Papillomavirus Receptors Related Genetic Variants in Cervical Cancer Screening.

To investigate the relationship between single nucleotide polymorphisms (SNPs) in human papillomavirus (HPV) receptor associated genes and HPV susceptibility and clinical outcomes in Chinese women, from October 2016 to March 2020, a total of 3,066 women were recruited for a 3-year prospective population-based cervical cancer screening clinical trial. The primary endpoint was histological cervical intraepithelial neoplasia 2 and worse (CIN2+). Twenty-nine SNPs of HPV receptor associated genes on women with available cytology residual samples at baseline were detected using MALDI-TOF MS. Eligible data were available for 2,938 women. Rs16894821 (GG versus AA, OR =1.71 [1.08 to 2.69]) and rs724236 (TT versus AA, OR = 1.73 [1.14 to 2.62]) in SDC2 were significantly related to the HPV susceptibility. And rs2575712 (TT versus GG, OR = 2.78 [1.22 to 6.36]) in SDC2 was associated with increased HPV 16/18 susceptibility. Four SNPs (rs1047057 and rs10510097 in FGFR2 gene, rs2575735 in SDC2 gene, and rs878949 in HSPG2 gene) were significantly associated with persistent HPV infection. Importantly, the genotypes of rs16894821 under recessive model (GG versus AA/AG, OR = 2.40 [1.12 to 5.15]) in SDC2 and rs11199993 under dominant model (GC/CC versus GG, OR = 1.64 [1.01 to 2.68]) in FGFR2 were significantly associated with the disease progression. Finally, SNPs showed comparable efficacy in detecting CIN2+ for the women infected with non-HPV16/18 compared with cervical cytology (sensitivity: 0.51 [0.36 to 0.66] versus 0.44 [0.30 to 0.60], specificity: 0.96 [0.96 to 0.97] versus 0.98 [0.97 to 0.99], positive predictive value: 0.23 [0.15 to 0.33] versus 0.33 [0.22 to 0.47], and negative predictive value: 0.99 [0.98 to 0.99] versus 0.99 [0.98 to 0.99]). SNPs in HPV receptor related genes may influence HPV susceptibilities and clinical outcomes in Chinese women. IMPORTANCE Virus receptors are known to mediate virus attachment and further lead to virus infection of the host cells. In the current study, we investigated the relationship between single nucleotide polymorphisms (SNPs) in human papillomavirus (HPV) receptor associated genes and HPV susceptibility and clinical outcomes in Chinese women, and to explore the new triaging strategy for non-16/18 high-risk HPV infection.

Exosomes derived from TGF-ß1-pretreated mesenchymal stem cells alleviate biliary ischemia-reperfusion injury through Jagged1/Notch1/SOX9 pathway.

BACKGROUND: This study aimed to evaluate the efficacy of exosomes (EXO) derived from TGF-ß1-pretreated mesenchymal stem cells (MSCs) on biliary ischemia reperfusion injury (IRI) and further reveal the possible mechanisms. METHODS: Bone marrow-derived MSCs were treated with exogenous TGF-ß1, Jagged1/Notch1/SOX9 pathway inhibitor LY450139, or their combination. Then, EXO were isolated from the culture supernatants and further characterized. After establishing IRI model of biliary epithelial cells (EpiCs), EXO derived from differently-treated MSCs were applied to detect their protective effects on EpiCs, and LY450139 was applied in EpiCs to detect the possible mechanisms after treatment with MSCs-EXO. EXO derived from differently-treated MSCs were further injected into the hepatic artery immediately after establishment of intrahepatic biliary IRI for animal studies. RESULTS: Pretreatment with TGF-ß1 significantly enhanced MSCs-EXO production and elevated the levels of massive miRNAs associated with anti-apoptosis and tissue repair, which were evidently decreased after TGF-ß1 plus LY450139 cotreatment. Notable improvement was observed in EpiCs after MSCs-EXO treatment, evidenced by reduced cellular apoptosis, increased cellular proliferation and declined oxidative stress, which were more evident in EpiCs that were treated with EXO derived from TGF-ß1-pretreated MSCs. However, application of EXO derived from TGF-ß1 plus LY450139-cotreated MSCs reversely enhanced cellular apoptosis, decreased cellular proliferation and anti-oxidants production. Interestingly, LY450139 application in EpiCs after treatment with MSCs-EXO also reversed the declined cellular apoptosis and enhanced oxidative stress induced by TGF-ß1 pretreatment. In animal studies, administration of EXO derived from TGF-ß1-pretreated MSCs more effectively attenuated biliary IRI through reducing oxidative stress, apoptosis, inflammation and enhancing the expression levels of TGF-ß1 and Jagged1/Notch1/SOX9 pathway-related markers, which were reversed after administration of EXO derived from TGF-ß1 plus LY450139-cotreated MSCs. CONCLUSION: Our results provided a vital insight that TGF-ß1 pretreatment endowed MSCs-EXO with stronger protective effects to improve biliary IRI via Jagged1/Notch1/SOX9 pathway.

Qualitative and Quantitative Determination of Decoquinate in Chicken Tissues by Gas Chromatography Tandem Mass Spectrometry.

A novel precolumn derivatization-GC-MS/MS method was developed for the determination of decoquinate residues in chicken tissues (muscle, liver, and kidney). The samples were extracted and purified by liquid-liquid extraction combined with solid-phase extraction and derivatized with acetic anhydride and pyridine. The recovery rates for decoquinate were 77.38~89.65%, and the intra-day and inter-day RSDs were 1.63~5.74% and 2.27~8.06%, respectively. The technique parameters meet the necessities for veterinary drug residue detection in China, the US, and the EU. Finally, the method was applied to analyze tissues of 60 chickens bought from a neighborhood supermarket, and solely one sample of chicken muscle contained 15.6 µg/kg decoquinate residue.

Favourable clinical, arthroscopic and radiographic outcomes after autologous osteoperiosteal transplantation for massive medial cystic osteochondral defects of the talus.

PURPOSE: The purpose of this study was to retrospectively evaluate the clinical, arthroscopic and radiological outcomes of autologous osteoperiosteal transplantation for massive cystic osteochondral defects of the talus. METHODS: Cases of autologous osteoperiosteal transplantation for medial massive cystic defects of the talus between 2014 and 2018 were reviewed. The visual analogue scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) score, Foot and Ankle Outcome Score (FAOS), and Ankle Activity Scale (AAS) were assessed preoperatively and postoperatively. The Magnetic Resonance Observation of Cartilage Tissue (MOCART) system and the International Cartilage Repair Society (ICRS) score were evaluated after surgery. The ability to return to daily activity and sport, as well as complications, were recorded. RESULTS: Twenty-one patients were available for follow-up, with a mean follow-up of 60.1 ± 11.7 months. All subscales of preoperative FAOS had significant (P < 0.001) improvement at the final follow-up. The mean AOFAS and VAS scores significantly (P < 0.001) improved from 52.4 ± 12.4 preoperatively to 90.9 ± 5.2 at the last follow-up and from 7.9 ± 0.8 to 1.5 ± 0.9, respectively. The mean AAS decreased from 6.0 ± 1.4 preinjury to 1.4 ± 0.9 postinjury and then increased to 4.6 ± 1.4 at the final follow-up (P < 0.001). All 21 patients resumed daily activities after a mean of 3.1 ± 1.0 months. Fifteen patients (71.4%) returned to sports after a mean of 12.9 ± 4.1 months. All patients underwent follow-up MRI with a mean MOCART score of 68.6 ± 5.9. Eleven patients underwent second-look arthroscopy, and the average ICRS was 9.4 ± 0.8. No donor site morbidity was found in any patient during the follow-up. CONCLUSION: Autologous osteoperiosteal transplantation provided favourable clinical, arthroscopic and radiographic outcomes in patients with massive cystic osteochondral defects of the talus during a minimum 3-year follow-up. LEVEL OF EVIDENCE: IV.