BatmanNet: bi-branch masked graph transformer autoencoder for molecular representation.

Although substantial efforts have been made using graph neural networks (GNNs) for artificial intelligence (AI)-driven drug discovery, effective molecular representation learning remains an open challenge, especially in the case of insufficient labeled molecules. Recent studies suggest that big GNN models pre-trained by self-supervised learning on unlabeled datasets enable better transfer performance in downstream molecular property prediction tasks. However, the approaches in these studies require multiple complex self-supervised tasks and large-scale datasets , which are time-consuming, computationally expensive and difficult to pre-train end-to-end. Here, we design a simple yet effective self-supervised strategy to simultaneously learn local and global information about molecules, and further propose a novel bi-branch masked graph transformer autoencoder (BatmanNet) to learn molecular representations. BatmanNet features two tailored complementary and asymmetric graph autoencoders to reconstruct the missing nodes and edges, respectively, from a masked molecular graph. With this design, BatmanNet can effectively capture the underlying structure and semantic information of molecules, thus improving the performance of molecular representation. BatmanNet achieves state-of-the-art results for multiple drug discovery tasks, including molecular properties prediction, drug-drug interaction and drug-target interaction, on 13 benchmark datasets, demonstrating its great potential and superiority in molecular representation learning.

Hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy for patients with locally advanced recurrent nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial.

BACKGROUND: Reirradiation in standard fractionation for locally advanced recurrent nasopharyngeal carcinoma after a previous course of high-dose radiotherapy is often associated with substantial late toxicity, negating its overall benefit. We therefore aimed to investigate the efficacy and safety of hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy. METHODS: This multicentre, randomised, open-label, phase 3 trial was done in three centres in Guangzhou, China. Eligible patients were aged 18-65 years with histopathologically confirmed undifferentiated or differentiated, non-keratinising, advanced locally recurrent nasopharyngeal carcinoma. Participants were randomly assigned (1:1) to either receive hyperfractionation (65 Gy in 54 fractions, given twice daily with an interfractional time interval of at least 6 h) or standard fractionation (60 Gy in 27 fractions, given once a day). Intensity-modulated radiotherapy was used in both groups. A computer program generated the assignment sequence and randomisation was stratified by treatment centre, recurrent tumour stage (T2-T3 vs T4), and recurrent nodal stage (N0 vs N1-N2), determined at the time of randomisation. The two primary endpoints were the incidence of severe late complications defined as the incidence of grade 3 or worse late radiation-induced complications occurring 3 months after the completion of radiotherapy until the latest follow-up in the safety population, and overall survival defined as the time interval from randomisation to death due to any cause in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02456506. FINDINGS: Between July 10, 2015, and Dec 23, 2019, 178 patients were screened for eligibility, 144 of whom were enrolled and randomly assigned to hyperfractionation or standard fractionation (n=72 in each group). 35 (24%) participants were women and 109 (76%) were men. After a median follow-up of 45·0 months (IQR 37·3-53·3), there was a significantly lower incidence of grade 3 or worse late radiation-induced toxicity in the hyperfractionation group (23 [34%] of 68 patients) versus the standard fractionation group (39 [57%] of 68 patients; between-group difference -23% [95% CI -39 to -7]; p=0·023). Patients in the hyperfractionation group had better 3-year overall survival than those in the standard fractionation group (74·6% [95% CI 64·4 to 84·8] vs 55·0% [43·4 to 66·6]; hazard ratio for death 0·54 [95% CI 0·33 to 0·88]; p=0·014). There were fewer grade 5 late complications in the hyperfractionation group (five [7%] nasal haemorrhage) than in the standard fractionation group (16 [24%], including two [3%] nasopharyngeal necrosis, 11 [16%] nasal haemorrhage, and three [4%] temporal lobe necrosis). INTERPRETATION: Hyperfractionated intensity-modulated radiotherapy could significantly decrease the rate of severe late complications and improve overall survival among patients with locally advanced recurrent nasopharyngeal carcinoma. Our findings suggest that hyperfractionated intensity-modulated radiotherapy could be used as the standard of care for these patients. FUNDING: Key-Area Research and Development of Guangdong Province, the National Natural Science Foundation of China, the Special Support Program for High-level Talents in Sun Yat-sen University Cancer Center, the Guangzhou Science and Technology Plan Project, and the National Ten Thousand Talents Program Science and Technology Innovation Leading Talents, Sun Yat-Sen University Clinical Research 5010 Program.

A modified diffusion-weighted magnetic resonance imaging-based model from the radiologist's perspective: improved performance in determining the surgical resectability of advanced high-grade serous ovarian cancer.

BACKGROUND: Complete resection of all visible lesions during primary debulking surgery is associated with the most favorable prognosis in patients with advanced high-grade serous ovarian cancer. An accurate preoperative assessment of resectability is pivotal for tailored management. OBJECTIVE: This study aimed to assess the potential value of a modified model that integrates the original 8 radiologic criteria of the Memorial Sloan Kettering Cancer Center model with imaging features of the subcapsular or diaphragm and mesenteric lesions depicted on diffusion-weighted magnetic resonance imaging and growth patterns of all lesions for predicting the resectability of advanced high-grade serous ovarian cancer. STUDY DESIGN: This study included 184 patients with high-grade serous ovarian cancer who underwent preoperative diffusion-weighted magnetic resonance imaging between December 2018 and May 2023 at 2 medical centers. The patient cohort was divided into 3 subsets, namely a study cohort (n=100), an internal validation cohort (n=46), and an external validation cohort (n=38). Preoperative radiologic evaluations were independently conducted by 2 radiologists using both the Memorial Sloan Kettering Cancer Center model and the modified diffusion-weighted magnetic resonance imaging-based model. The morphologic characteristics of the ovarian tumors depicted on magnetic resonance imaging were assessed as either mass-like or infiltrative, and transcriptomic analysis of the primary tumor samples was performed. Univariate and multivariate statistical analyses were performed. RESULTS: In the study cohort, both the scores derived using the Memorial Sloan Kettering Cancer Center (intraclass correlation coefficients of 0.980 and 0.959, respectively; both P<.001) and modified diffusion-weighted magnetic resonance imaging-based models (intraclass correlation coefficients of 0.962 and 0.940, respectively; both P<.001) demonstrated excellent intra- and interobserver agreement. The Memorial Sloan Kettering Cancer Center model (odds ratio, 1.825; 95% confidence interval, 1.390-2.395; P<.001) and the modified diffusion-weighted magnetic resonance imaging-based model (odds ratio, 1.776; 95% confidence interval, 1.410-2.238; P<.001) independently predicted surgical resectability. The modified diffusion-weighted magnetic resonance imaging-based model demonstrated improved predictive performance with an area under the curve of 0.867 in the study cohort and 0.806 and 0.913 in the internal and external validation cohorts, respectively. Using the modified diffusion-weighted magnetic resonance imaging-based model, patients with scores of 0 to 2, 3 to 4, 5 to 6, 7 to 10, and ≥11 achieved complete tumor debulking rates of 90.3%, 66.7%, 53.3%, 11.8%, and 0%, respectively. Most patients with incomplete tumor debulking had infiltrative tumors, and both the Memorial Sloan Kettering Cancer Center and the modified diffusion-weighted magnetic resonance imaging-based models yielded higher scores. The molecular differences between the 2 morphologic subtypes were identified. CONCLUSION: When compared with the Memorial Sloan Kettering Cancer Center model, the modified diffusion-weighted magnetic resonance imaging-based model demonstrated enhanced accuracy in the preoperative prediction of resectability for advanced high-grade serous ovarian cancer. Patients with scores of 0 to 6 were eligible for primary debulking surgery.

Brønsted Acid-Mediated Conversion of Naturally Abundant Lathyrane Diterpenes: Are Rare 10,11-seco-Lathyrane Diterpenes Artifacts?

The question of whether rare 10,11-seco-lathyranes are natural products or artifacts is thoughtfully considered after a Brønsted acid-mediated chemical conversion of naturally abundant 5/11/3 lathyrane type diterpenes into 10,11-seco-lathyranes was developed. Benefiting from this concise route, a series of 10,11-seco-lathyrane products (1-14) were smoothly synthesized. The conversion may involve an acid promoted cyclopropane ring opening accompanied by a double bond shift with final trapping of carbocation. The ease of this chemical conversion under mildly acidic conditions may imply that the 10,11-seco-lathyranes isolated to date are artifacts. This work not only develops a new modular synthetic strategy for efficient constructing rare 10,11-seco-lathyranes, but also provides a promising bioactive diterpene with excellent effect against the NO production on LPS-induced BV-2 cells.

AUF1-induced circular RNA hsa_circ_0010467 promotes platinum resistance of ovarian cancer through miR-637/LIF/STAT3 axis.

BACKGROUND: Increasing evidences has indicated that primary and acquired resistance of ovarian cancer (OC) to platinum is mediated by multiple molecular and cellular factors. Understanding these mechanisms could promote the therapeutic efficiency for patients with OC. METHODS: Here, we screened the expression pattern of circRNAs in samples derived from platinum-resistant and platinum-sensitive OC patients using RNA-sequencing (RNA-seq). The expression of hsa_circ_0010467 was validated by Sanger sequencing, RT-qPCR, and fluorescence in situ hybridization (FISH) assays. Overexpression and knockdown experiments were performed to explore the function of hsa_circ_0010467. The effects of hsa_circ_0010467 on enhancing platinum treatment were validated in OC cells, mouse model and patient-derived organoid (PDO). RNA pull-down, RNA immunoprecipitation (RIP), and dual-luciferase reporter assays were performed to investigate the interaction between hsa_circ_0010467 and proteins. RESULTS: Increased expression of hsa_circ_0010467 is observed in platinum-resistant OC cells, tissues and serum exosomes, which is positively correlated with advanced tumor stage and poor prognosis of OC patients. Hsa_circ_0010467 is found to maintain the platinum resistance via inducing tumor cell stemness, and silencing hsa_circ_0010467 substantially increases the efficacy of platinum treatment on inhibiting OC cell proliferation. Further investigation reveals that hsa_circ_0010467 acts as a miR-637 sponge to mediate the repressive effect of miR-637 on leukemia inhibitory factor (LIF) and activates the LIF/STAT3 signaling pathway. We further discover that AUF1 could promote the biogenesis of hsa_circ_0010467 in OC. CONCLUSION: Our study uncovers the mechanism that hsa_circ_0010467 mediates the platinum resistance of OC through AUF1/hsa_circ_0010467/miR-637/LIF/STAT3 axis, and provides potential targets for the treatment of platinum-resistant OC patients.

The Mechanism of Short-Circuit Oscillations in Automotive-Grade Multi-Chip Parallel Power Modules and an Effective Mitigation Approach.

This paper presents an in-depth analysis of the oscillation phenomenon occurring in multi-chip parallel automotive-grade power modules under short-circuit conditions and investigates three suppression methods. We tested and analyzed two commercial automotive-grade power modules, one containing two chips and the other containing a single chip, and found that short-circuit gate oscillations were more likely to occur in multi-chip parallel packaged modules than in single-chip packaged modules. Through experimental and simulation analyses, we observed that gate oscillations were mainly caused by the interaction between internal parasitic parameters of the module and the external drive circuit, and we found that high drive resistance and low common emitter inductance between parallel chips could effectively suppress gate voltage oscillations. We also analyzed the two mainstream suppression schemes, increasing the drive gate resistance and placing the drive capacitors in parallel. Unfortunately, we found that these suppression schemes were not ideal solutions because both schemes changed the switching characteristics of the power module. As an alternative, we propose a simple and effective solution that involves adding parallel connections between the parallel chips. Simulation calculations showed that this optimized method reduced the emitter inductance between parallel chips in the upper bridge arm by about 30% and in the lower bridge arm by 35%. Through short-circuit experiments conducted at different DC bus voltages, it has been verified that the new optimized solution effectively resolves gate oscillation issues without affecting the switching characteristics of the power module.

Heterogeneous treatment effects of metformin on risk of dementia in patients with type 2 diabetes: A longitudinal observational study.

INTRODUCTION: Little is known about the heterogeneous treatment effects of metformin on dementia risk in people with type 2 diabetes (T2D). METHODS: Participants (≥ 50 years) with T2D and normal cognition at baseline were identified from the National Alzheimer's Coordinating Center database (2005-2021). We applied a doubly robust learning approach to estimate risk differences (RD) with a 95% confidence interval (CI) for dementia risk between metformin use and no use in the overall population and subgroups identified through a decision tree model. RESULTS: Among 1393 participants, 104 developed dementia over a 4-year median follow-up. Metformin was significantly associated with a lower risk of dementia in the overall population (RD, -3.2%; 95% CI, -6.2% to -0.2%). We identified four subgroups with varied risks for dementia, defined by neuropsychiatric disorders, non-steroidal anti-inflammatory drugs, and antidepressant use. DISCUSSION: Metformin use was significantly associated with a lower risk of dementia in individuals with T2D, with significant variability among subgroups.

Anomalous Nernst Effect Induced Terahertz Emission in a Single Ferromagnetic Film.

Despite its important role in understanding ultrafast spin dynamics and revealing novel spin/orbit effects, the mechanism of the terahertz (THz) emission from a single ferromagnetic nanofilm upon a femtosecond laser pump still remains elusive. Recent experiments have shown exotic symmetry, which is not expected from the routinely adopted mechanism of ultrafast demagnetization. Here, by developing a bidirectional pump-THz emission spectroscopy and associated symmetry analysis method, we set a benchmark for the experimental distinction of the THz emission induced by various mechanisms. Our results unambiguously unveil a new mechanism─anomalous Nernst effect (ANE) induced THz emission due to the ultrafast temperature gradient created by a femtosecond laser. Quantitative analysis shows that the THz emission exhibits interesting thickness dependence where different mechanisms dominate at different thickness ranges. Our work not only clarifies the origin of the ferromagnetic-based THz emission but also offers a fertile platform for investigating the ultrafast optomagnetism and THz spintronics.

Oridonin loaded peptide nanovesicles alleviate nonalcoholic fatty liver disease in mice.

This study was to construct a nanovesicle delivery system to improve the loading efficiency and stability of ORI for the treatment of nonalcoholic fatty liver disease (NAFLD). This nanovesicles (NVs) exerted a narrow size distribution (195.6 ± 11.49 nm) and high entrapment efficiency (84.46 ± 1.34%). In vitro cell studies demonstrated that the NVs treatment enhanced the cellular uptake of ORI and reduced lipid over-accumulation and total cholesterol levels in NAFLD cell model. At the same time, in vivo study proved that, compared with the normal group, the model group mice showed a decrease in body weight, a significant increase in liver index (6.71 ± 0.62, p < 0.01), and symptoms of liver lipid accumulation, lipid vesicles, and liver tissue fibrosis. Compared with the model group, after high-dose ORI NVs intervention, mice gained weight, decreased liver index (4.69 ± 0.55, p < 0.01), reduced hepatic lipid droplet vacuoles, reduced lipid accumulation (reduced oil red area, p < 0.001), and alleviated the degree of liver fibrosis (reduced blue collagen area, p < 0.001). In conclusion, ORI/HP-ß-CD/H9-HePC NVs showed specific liver accumulation and improved therapeutic effects, the nano drug loading system provides a promising strategy for the encapsulation of ORI to effectively alleviate the process of NAFLD.

Construction of Genetically Encoded Light-Up RNA Aptamers for Label-free and Ultrasensitive Detection of CircRNAs in Cancer Cells and Tissues.

Circular RNAs (circRNAs) as endogenous non-coding RNAs are characterized by covalently closed circular structures, and they widely exist in mammalian cells. The aberrant expression of circRNAs may result in various diseases. Herein, we demonstrate the construction of genetically encoded light-up RNA aptamers for ultrasensitive and label-free detection of circRNA mitochondrial tRNA translation optimization 1 (circMTO1) in cancer cells and tissues. The light-up RNA aptamers are generated by proximity ligation-activated recombinase polymerase amplification (RPA)-assisted transcription amplification. When circMTO1 is present, it initiates the proximity ligation reaction, activating RPA to produce numerous long double-stranded DNAs containing T7 promoters. Subsequently, the RPA products are identified by T7 RNA polymerase, initiating the transcription amplification reaction to generate abundant Spinach RNA aptamers. Spinach RNA aptamers can bind with DFHBI (3,5-difluoro-4-hydroxybenzylidene imidazolidinone) dye to produce a distinct fluorescence signal with near-zero background. This biosensor exhibits excellent selectivity and high sensitivity with a limit of detection of 2.54 aM. It can accurately monitor cellular circMTO1 at the single-cell level and discriminate the expression of circMTO1 between breast cancer patient tissues and healthy tissues. Notably, this biosensor can be employed to measure other nucleic acids by altering the corresponding target recognition sequences, providing a valuable platform for cancer diagnosis and biomedical study.

Activation of Toll-like receptor 3 inhibits HIV infection of human iPSC-derived microglia.

As a key immune cell in the brain, microglia are essential for protecting the central nervous system (CNS) from viral infections, including HIV. Microglia possess functional Toll-like receptor 3 (TLR3), a key viral sensor for activating interferon (IFN) signaling pathway-mediated antiviral immunity. We, therefore, studied the effect of poly (I:C), a synthetic ligand of TLR3, on the activation of the intracellular innate immunity against HIV in human iPSC-derived microglia (iMg). We found that poly (I:C) treatment of iMg effectively inhibits HIV infection/replication at both mRNA and protein levels. Investigations of the mechanisms revealed that TLR3 activation of iMg by poly (I:C) induced the expression of both type I and type III IFNs. Compared with untreated cells, the poly (I:C)-treated iMg expressed significantly higher levels of IFN-stimulated genes (ISGs) with known anti-HIV activities (ISG15, MxB, Viperin, MxA, and OAS-1). In addition, TLR3 activation elicited the expression of the HIV entry coreceptor CCR5 ligands (CC chemokines) in iMg. Furthermore, the transcriptional profile analysis showed that poly (I:C)-treated cells had the upregulated IFN signaling genes (ISG15, ISG20, IFITM1, IFITM2, IFITM3, IFITM10, APOBEC3A, OAS-2, MxA, and MxB) and the increased CC chemokine signaling genes (CCL1, CCL2, CCL3, CCL4, and CCL15). These observations indicate that TLR3 is a potential therapy target for activating the intracellular innate immunity against HIV infection/replication in human microglial cells. Therefore, further studies with animal models and clinical specimens are necessary to determine the role of TLR3 activation-driven antiviral response in the control and elimination of HIV in infected host cells.

Human Parvovirus B19 May Be a Risk Factor in Myasthenia Gravis with Thymoma.

PURPOSE: Our previous studies have demonstrated that human parvovirus B19 (B19V) is involved in the pathogenesis of thymic hyperplasia-associated myasthenia gravis (MG). However, more cases need to be assessed to further elucidate the relationship between this virus and thymoma-associated MG. MATERIALS AND METHODS: The clinicopathological characteristics, presence of B19V DNA, and B19V VP2 capsid protein expression of 708 cases of thymomas were investigated using nested polymerase chain reaction (PCR), TaqMan quantitative (q) PCR, immunohistochemistry, fluorescent multiplex immunohistochemistry, and electron microscopy. RESULTS: Patients with MG or ectopic germinal centers (GCs) were significantly younger than those without MG (P < 0.0001) or GCs (P = 0.0001). Moreover, significantly more GCs were detected in thymomas associated with MG than in those without MG (P < 0.0001). The results of nested PCR and TaqMan qPCR were consistent, and B19V DNA positivity was only associated with presence of GCs (P = 0.011). Immunohistochemically, positive staining was primarily detected in neoplastic thymic epithelial cells (TECs) and ectopic GCs. The positive rate of B19V VP2 was significantly higher in thymoma with MG or GCs than in thymoma without MG (P = 0.004) or GCs (P = 0.006). Electron microscopy showed B19V particles in the nuclei of neoplastic TECs and B cells from GCs. CONCLUSIONS: We conclude that the pathogenesis of MG is closely associated with the presence of GCs, and B19V infection is plausibly an essential contributor to formation of ectopic GCs in thymoma. To the best of the authors' knowledge, this is the first study to elucidate the role of B19V in thymoma-associated MG and provide new ideas for exploring the etiopathogenic mechanism of MG.

Head-to-head comparison of [18F]-FDG and [68 Ga]-DOTA-FAPI-04 PET/CT for radiological evaluation of platinum-sensitive recurrent ovarian cancer.

PURPOSE: Precise radiological evaluation is pivotal for the management of platinum-sensitive recurrent ovarian cancer. We aimed to compare the value of [68 Ga]-FAPI and [18F]-FDG PET/CT for the detection of relapsed lesions. METHODS: Twenty-nine suspected platinum-sensitive recurrent ovarian cancers were enrolled from January 2022 to July 2022. [18F]-FDG and [68 Ga]-FAPI PET/CT were obtained within 1 week for radiological evaluation. Treatment strategies, visual scores, and Eisenkop scores were recorded. A paired T test was used to compare differences between two scans. Sensitivity, specificity, PPV, NPV, and accuracy were also evaluated. RESULTS: Up to 22 (75.86%) patients displayed inconsistency between two scans. Among them, 4 patients with negative [18F]-FDG imaging had measurable lesions in [68 Ga]-FAPI scans. The treatment strategies were changed in 5 patients (17.24%) due to discrepancies. Finally, 15 (35.7%) patients underwent surgeries, and 14 patients achieved complete resection, except for 1 patient who had milliarc residual disease. TBR, but not SUVmax, of [68 Ga]-FAPI was significantly higher than that of [18F]-FDG in recurrent lesions. Compared with [18F]-FDG, [68 Ga]-FAPI PET presented higher sensitivity and accuracy for lesion detection (96.30% vs. 49.07% and 97.40% vs. 63.87%, respectively). Additionally, [68 Ga]-FAPI PET showed a much higher visual score than [18F]-FDG PET (41 vs. 4), especially for peritoneal metastasis (35 vs. 1). [68 Ga]-FAPI PET also presented a larger tumor burden than [18F]-FDG according to the Eisenkop score (27 vs. 16, p = 0.025). CONCLUSIONS: [68 Ga]-FAPI was superior to [18F]-FDG PET/CT for the detection of recurrent lesions, which is pivotal for the individualized management of platinum-sensitive recurrent ovarian cancer.

Diffusion-weighted magnetic resonance imaging for the pre-operative evaluation of epithelial ovarian cancer patients.

OBJECTIVE: To investigate the value diffusion-weighted magnetic resonance imaging (DWI/MR) in the selection of ovarian cancer patients suitable for primary debulking surgery. METHODS: Patients with suspected ovarian cancer who underwent pre-operative DWI/MR were enrolled between April 2020 and March 2022. All participants received preoperative clinic-radiological assessment according to the Suidan criteria for R0 resection with a predictive score. Data for patients with primary debulking surgery were prospectively recorded. The diagnostic value was calculated with ROC curves, and the cut-off value for the predictive score was also explored. RESULTS: 80 patients with primary debulking surgery were included in the final analysis. The majority (97.5%) of patients were at advanced stage (III-IV), and 90.0% of patients had high-grade serous ovarian histology. 46 (57.5%) patients had no residual disease (R0), and 27 (33.8%) patients had optimal debulking surgery with zzmacroscopic disease less than or equal to 1 cm (R1). Patients with BRCA1 mutation had lower R0 resection rate, higher R1 resection rate compared with wild-type patients (42.9% vs 63.0%, 50.0% vs 29.6%, respectively). The median (range) predictive score was 4 (0-13), and the AUC for R0 resection was 0.742 (0.632-0.853). The R0 rates for patients with predictive score 0-2, 3-5, and ≥ 6 were 77.8%, 62.5% and 23.8%, respectively. CONCLUSION: DWI/MR was a sufficient technique for pre-operative evaluation of ovarian cancer. Patients with predictive score 0-5 were suitable for primary debulking surgery at our institution.

Clinical Comparative Analyses of Thymectomy Between Subxiphoid and Subcostal Arch Thoracoscopic Resection and Median Sternotomy for the Treatment of Thymoma With Myasthenia Gravis in Chinese Patients.

INTRODUCTION: This study aims to retrospectively compare the efficacy and safety of subxiphoid and subcostal arch thoracoscopic resection (SR) and the median sternotomy (MS) for thymoma with myasthenia gravis (MG) via propensity-matched analysis. METHODS: We retrospectively analyzed 502 patients with thymoma and MG in Tangdu Hospital of the Fourth Military Medical University from December 2012 to December 2017. The patients were allocated to SR group (n = 424) and MS group (n = 78). Perioperative outcomes were compared between SR group and MS group by using propensity-matched analysis. RESULTS: All SR and MS operations were accomplished successfully. Most postoperative outcomes between the two groups showed no significant difference such as remission of MG and postoperative complication (P > 0.05). There were statistically significant differences between MS group and SR group in operation time [(116.3 ± 33.7) min versus (52.2 ± 31.3) min], intraoperative blood loss [(145.2 ± 26.7) mL versus (51.2 ± 10.3) mL], chest drainage duration (3.4 d versus 0 d), days of hospital-stay (5.2 d versus 2.7 d), patient satisfaction score (5.9 ± 2.3 versus 8.7 ± 1.2), the incidence of complications and pain scores, with all P values < 0.05. CONCLUSIONS: This study suggests that subxiphoid and subcostal arch thoracoscopic resection is a less invasive procedure with good safety and feasibility as compared with median sternotomy for thymoma with myasthenia gravis.

Increased TT-TG distance caused by excessive tibiofemoral rotation predicts poor clinical outcomes after tibial tubercle osteotomy in recurrent patellar dislocation.

PURPOSE: To compare clinical outcome between recurrent patellar dislocation (RPD) with or without actual tibial tubercle lateralisation (TTL) after medial patellofemoral ligament reconstruction (MPFL-R) combined with tibial tubercle transfer. METHODS: From 2015 to 2018, a total of 172 knees with RPD and a tibial tubercle-trochlear groove (TT-TG) distance of > 20 mm were treated with MPFL-R combined with tibial tubercle transfer. Patients were divided into the lateralisation group (TT-PCL > 24 mm, n = 74) and the nonlateralisation group (TT-PCL ≤ 24 mm, n = 60) based on the presence or absence of actual TTL (TT-PCL > 24 mm). Clinical outcomes were assessed postoperatively at a minimum of 2 years. Second-look arthroscopic evaluations were available for 84 knees to assess cartilage damage. RESULTS: A total of 134 knees with a median follow-up time of 32 months were included. Tibiofemoral rotation (TFR) was significantly higher in the nonlateralisation group than in the lateralisation group (15.4° vs. 9.4°, P < 0.001). At the final follow-up, the nonlateralisation group had significantly lower Kujala (78.2 vs. 86.4, P = 0.001) and Lysholm (80.3 vs. 88.2, P = 0.003) scores than the lateralisation group. At the time of the second-look arthroscopic assessment, 38.9% of the patients in the nonlateralisation group showed cartilage worsening in the medial patellar facet that was significantly higher than that in the lateralisation group (38.9% vs. 12.5%, P = 0.015). CONCLUSION: Patients with RPD and an increased TT-TG distance of > 20 mm but without actual tibial tubercle lateralisation benefit less from tibial tubercle transfer than patients with actual tibial tubercle lateralisation, which may be related to the significantly higher tibiofemoral rotation angle of the former. LEVEL OF EVIDENCE: III.

Ferulic Acid Induces Autophagy and Apoptosis in Colon Cancer CT26 Cells via the MAPK Pathway.

Ferulic acid (FA) is a bioactive compound found in traditional Chinese herbal medicine; for example, it is present in Xinjiang Ferula, but also in strong-flavor Chinese baijiu. FA has been shown to play a crucial role in treating oxidative stress, skin whitening, and eye diseases. In this study, the potential role of FA as a means of inducing apoptosis and inhibiting colon cancer induced by the transplantation of CT26 cells was investigated. The results show that FA adjuvant treatment caused an upregulation in the expression of genes related to autophagy while simultaneously suppressing the expression of inflammatory response elements and improving the bodyweight, glutamic pyruvic transaminase (ALT), and glutamic oxaloacetic transaminase (AST) in vivo. Furthermore, FA inhibited the proliferation of CT26 cells and induced apoptosis, specifically by activating the phosphorylation of ERK and JNK to enhance the essential proteins BCL-2 and BAX in the apoptosis pathway. These results suggest that FA could be a promising auxiliary therapeutic agent for the treatment of colon cancer. Further research is needed to better understand the mechanisms underlying the beneficial effects of FA and its synergistic effects with other compounds.

Clinical efficacy of flap transplantation combined with vacuum sealing drainage and methylprednisolone and cyclosporine in the treatment of pyoderma gangrenosum.

This study was aimed to evaluate the clinical efficacy of flap transplantation combined with vacuum sealing drainage and methylprednisolone and cyclosporine in the treatment of ulcer wound of patients with pyoderma gangrenosum (PG). From August 2014 to February 2022, 30 patients with pyoderma gangrenosum ulcer wounds were selected as the research objects and randomly divided into the observation group (n = 12) and the control group (n = 18) in this retrospective study. The patients in observation group were treated with VSD combined with flap transplantation and immunosuppressive agent treatment, while the control group was treated with normal dressing change combined with hormone and cyclosporine. The ulcer wound healing time and dressing change times were compared between the two groups. All the 30 cases of two groups healed after corresponding treatment. The wound healing time of ulcer in the observation group was 35-40 days, with an average healing time of (35.83 ± 1.95) days, and the wound healing time of the control group was 60-200 days, with an average healing time of (44.14 ± 9.67) days. The healing time of observation groups was significantly shorter than that in the control group (t = 4.652, P < .05). The frequency of dressing change in the observation group was seven-eight times, with an average of (7.17 ± 0.39) times, and the frequency of dressing change in the control group was 75-86 times, with an average of (79.22 ± 3.62) times. The difference between the two groups was significant (t = 6.214, P < .05). The treatment of VSD combined with flap transplantation and immunosuppressive agent treatment promote ulcer wound healing of pyoderma gangrenosum.

[Immune-Related Pancreatitis Caused by Immune Checkpoint Inhibitor Nivolumab:Report of One Case].

In recent years,great progress has been achieved in the application of immune checkpoint inhibitors (ICI) in tumor immunotherapy.However,a variety of adverse reactions induced by ICI have been reported.Despite the high overall incidence of adverse reactions caused by ICI,some adverse reactions,such as immune-related pancreatitis,are rare in clinical practice.In this paper,a case of immune-related pancreatitis after treatment of advanced gastric cancer with nivolumab was identified.We analyzed the cause,treatment,incidence,and risk factors of the adverse reaction,aiming to improve the clinical diagnosis,treatment,and safe medication of rare adverse reactions associated with ICI.

Adenophorone, An Unprecedented Sesquiterpene from Eupatorium adenophorum: Structural Elucidation, Bioinspired Total Synthesis and Neuroprotective Activity Evaluation.

(-)-Adenophorone (1), a caged polycyclic sesquiterpene featuring an unprecedented tricyclo[4.3.1.05,9 ]decane skeleton, was isolated from Eupatorium adenopharum Spreng. The structure of 1 was unambiguously established by a combination of spectroscopic analysis, X-ray crystallography, and bioinspired total synthesis. Key synthetic features include a sequential Reformatsky/oxidation/regio- and stereoselective hydrogenation, and subsequent merged MBH-Tsuji-Trost cyclization. The concise synthetic sequence efficiently constructs the bicyclic skeleton of cadinene sesquiterpene (+)-euptox A (2) in 8 steps from commercially available monoterpene (-)-carvone (6), with outstanding performance on diastereocontrol. The bioinspired synthesis of 1 was achieved from 2, a plausible biogenetic precursor, via transannular Michael addition. This work provides experimental evidence of our proposed biosynthetic hypothesis of 1. Additionally, compound 1 showed potent neuroprotective activity in H2 O2 -treated SH-SY5Y and PC12 cells.