Comparison efficacy and safety of total laparoscopic gastrectomy and laparoscopically assisted total gastrectomy in treatment of gastric cancer.

BACKGROUND: The development of laparoscopic technology has provided a new choice for surgery of gastric cancer (GC), but the advantages and disadvantages of laparoscopic total gastrectomy (LTG) and laparoscopic-assisted total gastrectomy (LATG) in treatment effect and safety are still controversial. The purpose of this study is to compare the efficacy and safety of the two methods in the treatment of GC, and to provide a basis for clinical decision-making. AIM: To compare the efficacy of totally LTG (TLTG) and LATG in the context of radical gastrectomy for GC. Additionally, we investigated the safety and feasibility of the total laparoscopic esophagojejunostomy technique. METHODS: Literature on comparative studies of the above two surgical methods for GC (TLTG group and LATG group) published before September 2022 were searched in the PubMed, Web of Science, Wanfang Database, CNKI, and other Chinese and English databases. In addition, the following search keywords were used: Gastric cancer, total gastrectomy, total laparoscopy, laparoscopy-assisted, esophagojejunal anastomosis, gastric/stomach cancer, total gastrectomy, totally/completely laparoscopic, laparoscopic assisted/laparoscopy assisted/laparoscopically assisted, and esophagojejunostomy/esophagojejunal anastomosis. Review Manager 5.3 software was used for the meta-analysis after two researchers independently screened the literature, extracted the data, and evaluated the risk of bias in the included studies. RESULTS: After layer-by-layer screening, 258 pieces of literature were recovered, and 11 of those pieces were eventually included. This resulted in a sample size of 2421 instances, with 1115 cases falling into the TLTG group and 1306 cases into the LATG group. Age or sex differences between the two groups were not statistically significant, according to the meta-analysis, however the average body mass index of the TLTG group was considerably higher than that of the LATG group (P = 0.01). Compared with those in the LATG group, the incision length in the TLTG group was significantly shorter (P < 0.001), the amount of intraoperative blood loss was significantly lower (P = 0.003), the number of lymph nodes removed was significantly greater (P = 0.04), and the time of first postoperative feeding and postoperative hospitalization were also significantly shorter (P = 0.03 and 0.02, respectively). There were no significant differences in tumor size, length of proximal incisal margin, total operation time, anastomotic time, postoperative pain score, postoperative anal exhaust time, postoperative anastomosis-related complications (including anastomotic fistula, anastomotic stenosis, and anastomotic hemorrhage), or overall postoperative complication rate (P > 0.05). CONCLUSION: TLTG and esophagojejunostomy are safe and feasible. Compared with LATG, TLTG has the advantages of less trauma, less bleeding, easier access to lymph nodes, and faster postoperative recovery, and TLTG is also suitable for obese patients.

Application of prostate resectoscope in the treatment of massive rectal bleeding after transrectal prostate puncture.

BACKGROUND: Ultrasound-guided prostate biopsy is a reliable diagnostic procedure for prostate cancer diagnosis with minimal procedure-related trauma. However, complications, such as massive rectal bleeding may occur after the puncture. We hypothesized that using a transrectal resectoscope could help treat massive rectal bleeding after transrectal prostate punctures. AIM: To identify a simple and effective treatment for massive rectal bleeding after transrectal prostate punctures. METHODS: Patients requiring treatment for massive rectal bleeding after transrectal prostate punctures were included. A SIMAI resectoscope was inserted through the anus. Direct electrocoagulation was performed for superficial bleeding points. Part of the rectal mucosa or surface muscle layer was removed to expose deep bleeding points, followed by electrocoagulation. An electric cutting ring was used to compress and stop the bleeding for jet-like points before electrocoagulation. The fluid color in the drainage tube was monitored postoperatively for continuous bleeding. RESULTS: Eight patients were included from 2012 to 2022. None of the patients with massive rectal bleeding after the transrectal prostate punctures improved with conventional conservative and blood transfusion treatments. Two patients had an inferior artery embolism, and digital subtraction angiography was ineffective. All patients received emergency transanal prostate resection, which immediately stopped the bleeding. Four days after the procedure, the patients had recovered and were discharged. CONCLUSION: Using a transanal prostate resection instrument is a simple, safe, and effective method for treating massive rectal bleeding after transrectal prostate punctures.

Association between serum total cholesterol and the development of gastric cancer: A two-way two-sample Mendelian randomization study.

Previous epidemiologic studies have suggested a potential negative correlation between total cholesterol (TC) and Gastric cancer (GC); however, several observational studies have shown conflicting results and have failed to provide definitive evidence for a causal relationship between TC and GC. Therefore, we conducted a 2-sample bidirectional Mendelian randomization (MR) study to explore the genetic correlation and potential causal relationship between the 2 variables. We screened for single nucleotide polymorphisms (SNPs) associated with TC and GC utilizing a large-scale genome-wide association study (GWAS) public database. The causal relationship was analyzed using 5 MR analysis methods: inverse variance weighting (IVW), weighted median, MR-Egger regression, weighted mode, and simple mode. Additionally, reverse MR analysis was performed to evaluate the possibility of reverse causality. Sensitivity analyses were conducted, including heterogeneity tests, horizontal multiple validity tests, and leave-one-out tests. After meticulous screening, 79 SNPs were identified as instrumental variables (IVs). The IVW method revealed a causal relationship between TC and GC (OR = 0.844; 95% CI: 0.741-0.961; P = .01). Sensitivity analyses did not detect significant horizontal pleiotropy. Though heterogeneity was observed in the forward MR analysis (IVW, Qp = 0.0006), the results remained reliable as we utilized the IVW random-effects model as the primary analytical method. Furthermore, inverse MR analysis found no evidence of reverse causality between TC and GC, effectively ruling out the influence of GC on the reverse causality of TC. Our MR study provided evidence of a causal association between TC and GC, suggesting that TC acts as a protective factor against GC due to its negative association with the disease.

Numerical Simulation of Electromagnetic-Thermal-Fluid Coupling for the Deformation Behavior of Titanium-Aluminum Alloy under Electromagnetic Levitation.

Electromagnetic levitation (EML) is a good method for high-temperature processing of reactive materials such as titanium-aluminum (Ti-Al) alloys. In this study, the oscillation and deformation processes of Ti-48Al-2Cr alloy specimens at different high-frequency currents during the EML process were simulated using the Finite Element Method and Arbitrary Lagrangian-Eulerian (ALE) methods. The data of oscillation, stabilization time, deformation, and distribution of electromagnetic-thermal-fluid fields were finally obtained. The accuracy of the simulation results was verified by EML experiments. The results show the following: the strength and distribution of the induced magnetic field inside the molten droplet are determined by the high-frequency current; under the coupling effect of the electromagnetic field, thermal field, and fluid field, the temperature rise of electromagnetic heating is rapid, and accompanied by strong stirring, resulting in a uniform distribution of the internal temperature and a small temperature difference. Under the joint action of gravity and Lorentz force, the molten droplets are first within a damped oscillation and then tend to stabilize with time, and finally maintain the "near rhombus" shape.

Risk factors of missed early gastric cancer in endoscopic resected population: a retrospective, case-control study.

BACKGROUND: Missed early gastric cancer (MEGC) is prevalent during esophagogastroduodenoscopy (EGD), which is the first-line recommended strategy for detecting early gastric cancer (EGC). Hence, we explored the risk factors for MEGC and different types of MEGC, based on the endoscopic resected population. METHODS: This retrospective, case-control study was conducted at Nanjing Drum Tower Hospital (NJDTH). We included patients who were diagnosed with EGC during screening EGD, underwent endoscopic resection, and were confirmed by postoperative pathology at the NJDTH from January 2014 to December 2021, and classified them into different types according to the different root causes of misses. Univariable, multivariable, subgroup and propensity score analyses were used to explore the risk factors for MEGC and different types of MEGC. RESULTS: A total of 447 patients, comprising 345 with initially detected early gastric cancer (IDEGC) and 102 with MEGC, were included in this study. Larger size (≥ 1 cm) (OR 0.45, 95% CI 0.27-0.74, P = 0.002) and invasion depth of submucosa (OR 0.26, 95% CI 0.10-0.69, P = 0.007) were negatively associated with MEGC. Use of sedation (OR 0.32, 95% CI 0.20-0.52, P < 0.001) and longer observation time (OR 0.60, 95% CI 0.37-0.96, P = 0.034) exhibited protective effect on MEGC. CONCLUSIONS: Smaller and more superficial EGC lesions are more susceptible to misdiagnosis. The use of sedation and prolonged observation time during EGD could help reduce the occurrence of MEGC.

Coexistence of adeno-associated virus 2 with adenovirus 18 or herpesvirus may be associated with severe lingual papillomatosis in an immunocompromised individual.

Next-generation sequencing (NGS) has significantly improved the accuracy and efficiency of pathogen diagnosis for a wide range of diseases. In this study, viral metagenomics analysis was conducted on fecal and tissue samples from a 13-year-old recipient of hematopoietic stem cell transplantation (HSCT) afflicted with severe lingual papillomatosis. The analysis revealed a high abundance of adeno-associated virus 2 (AAV2), alongside potential helper viruses, herpesvirus type 1 (HSV-1), and the uncommon adenovirus serotype 18 (AdV18). Although a direct causal relationship was not definitively established, the concurrence of these viruses indicated a plausible link to the development of severe lingual papillomatosis in immunocompromised individuals. Notably, the study generated a complete genome sequence of AdV18, offering insights into adenovirus genetic variability, origin, and pathogenicity. Noteworthy findings include three amino acid substitutions in the polymerase and one in the hexon, distinguishing them from previously published strains of AdV18. Phylogenetic analysis unveiled a close relationship between both the polymerase and hexon regions of AdV18 in our study and previously reported AdV18 sequences. This study underscores the pivotal role of comprehensive viral scrutiny in elucidating infections among HSCT patients with lingual papillomatosis.

Reconstitution of peripheral blood T cell receptor ß immune repertoire in immune checkpoint inhibitors associated myocarditis.

PURPOSE: Immune checkpoint inhibitors (ICIs)-associated myocarditis was a rare yet severe complication observed in individuals undergoing immunotherapy. This study investigated the immune status and characteristics of patients diagnosed with ICIs- associated myocarditis. METHODS: A total of seven patients diagnosed with ICIs-associated myocarditis were included in the study, while five tumor patients without myocarditis were recruited as reference controls. Additionally, 30 healthy individuals were recruited as blank controls. Biochemical indices, electrocardiogram, and echocardiography measurements were obtained both prior to and following the occurrence of myocarditis. High-throughput sequencing of T cell receptor (TCR) was employed to assess the diversity and distribution characteristics of TCR CDR3 length, as well as the diversity of variable (V) and joining (J) genes of T lymphocytes in peripheral blood. RESULTS: In the seven patients with ICIs-associated myocarditis, Troponin T (TNT) levels exhibited a significant increase following myocarditis, while other parameters such as brain natriuretic peptide (BNP), QTc interval, and left ventricular ejection fraction (LVEF) did not show any significant differences. Through sequencing, it was observed that the diversity and uniformity of CDR3 in the ICIs-associated myocarditis patients were significantly diminished. Additionally, the distribution of CDR3 nucleotides deviated from normality, and variations in the utilization of V and J gene segments. CONCLUSION: The reconstitution of the TCR immune repertoire may play a pivotal role in the recognition of antigens in patients with ICIs-associated myocarditis.

Robot-assisted total knee arthroplasty system provides more precise control of the femoral rotation angle: A retrospective study.

BACKGROUND: Rotational alignment in total knee arthroplasty (TKA) is a crucial technical point that needs attention. We conducted a retrospective study to investigate whether a new robot-assisted TKA (RA-TKA) could improve the accuracy of rotational alignment and whether rotational alignment affects postoperative pain and functional evaluation of the knee. METHODS: A total of 136 consecutive patients who underwent TKA were included in this study. Half of the patients underwent RA-TKA and the other half underwent conventional TKA (CON-TKA) by the same group of surgeons. Collect the relevant parameters. RESULTS: The postoperative femoral rotation angle (FRA) was -0.72 ± 2.59° in the robot-assisted group and 1.13 ± 2.73° in the conventional group, and were statistically significantly different (p < 0.001). CONCLUSION: This study provides preliminary evidence that the RA-TKA provides more precise control of FRA than CON-TKA, and verifies that tibial rotation angle and combined rotation angle affect postoperative knee pain and functional evaluation.

Case report: Rapidly progressive desmoid tumor after surgery for esophagogastric junction cancer and slowly progressive primary desmoid tumor: a report of two cases and literature review.

Background: Desmoid tumor (DT) is a rare locally aggressive but non-metastatic mesenchymal soft tissue neoplasm that predominantly occurs in the abdominal wall, abdominal cavity, and extremities. Its occurrence in the mesentery is relatively uncommon. Case reports: This article reports two cases of desmoid tumor treated at the Department of Gastrointestinal Surgery, Weifang People's Hospital. The first case was a 59-year-old male patient who had previously undergone surgery for esophagogastric junction cancer. Postoperatively, he developed an intra-abdominal mass that rapidly increased in size within three months. The second case was a 60-year-old male patient who incidentally discovered a mass in the left lower abdomen. Both patients underwent surgical treatment, and the postoperative pathological diagnosis was mesenteric desmoid tumor. Conclusion: The treatment of desmoid tumor remains challenging. Simple surgical resection often yields unsatisfactory outcomes, and the efficacy of adjuvant radiotherapy and chemotherapy is also limited. Further research and clinical practice are necessary to improve diagnostic and therapeutic strategies, aiming to enhance patient survival and quality of life.

Tuning the D-Band Center of Bi2S3─MoS2 Heterostructure Towards Superior Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries are one of the most promising energy storage devices due to their environmental friendliness, low cost, and high specific capacity. However, the slow electrochemical kinetics and the "shuttle effect" have seriously hindered their commercialization. Herein, the nanoflower Bi2S3─MoS2 (BMS) heterostructure is synthesized by a two-step hydrothermal method, and then the Bi2S3─MoS2-Polypropylene (BMS-PP) interlayer is constructed. The heterostructure is rich in active sites, in which BMS has strong adsorption to lithium polysulfides (LiPSs) and can effectively anchor LiPSs while catalyzing LiPSs and promote the redox of Li2S at the same time, which can improve the utilization of active substances. More importantly, the d-band center can be tuned by the formation of Bi2S3─MoS2 heterostructure. Thus, Li-S batteries containing the BMS-PP interlayer show excellent rate performance (841.6 mAh g-1 at 5 C) and cycling performance (70.3% capacity retention after 500 cycles at 3 C). This work provides a new route for high-performance lithium-sulfur batteries.

Association between renal α-klotho and renal pathology among patients with chronic kidney disease.

INTRODUCTION: This study was designed to investigate whether renal α-klotho levels are associated with renal pathology. This is the first report on patients with chronic kidney disease (CKD). METHODS: We conducted a retrospective observational study. A total of 65 CKD patients were enrolled. Serum and renal biopsy samples were collected. Estimated glomerular filtration rate (eGFR) was examined by biochemical test. And α-klotho expressions were assessed by RT-PCR and immunohistochemistry. In addition, detailed microscopic findings were reviewed. RESULTS: Renal α-klotho levels are associated positively with eGFR, and negatively with renal pathology, including interstitial fibrosis, inflammatory cell infiltration, and tubular atrophy. CONCLUSIONS: The renal α-klotho is related to renal pathology.

Effectiveness and Safety of Anlotinib Combined with PD-1 Blockades in Patients with Previously Immunotherapy Treated Advanced Non-Small Cell Lung Cancer: A Retrospective Exploratory Study.

Objective: This study aimed to investigate the effectiveness and tolerability of anlotinib plus PD-1 blockades in patients with previously immunotherapy treated advanced non-small-cell lung cancer (NSCLC). Methods: A total of 67 patients with previously immunotherapy treated advanced NSCLC who received anlotinib plus PD-1 blockades in clinical practice were screened retrospectively. All the PD-1 blockades used in this study were approved in China and consisted of sintilimab, camrelizumab, tislelizumab and pembrolizumab. Effectiveness and safety of anlotinib plus PD-1 blockades were assessed, and all patients were followed up regularly. Clinical significance between response status to previous immune-related treatment regimens and therapeutic outcomes of anlotinib plus PD-1 blockades was further explored. Results: The best overall response among the 67 patients suggested that a partial response was observed in 16 patients, stable disease was noted in 41 patients and progressive disease was found in 10 patients, which yielded an objective response rate of 23.9% (95% CI: 14.3-35.9%) and a disease control rate of 85.1% (95% CI: 74.3-92.6%). Prognostic outcomes indicated that the median progression-free survival (PFS) was 6.1 months (95% CI: 2.37-9.83) and the median overall survival (OS) was 16.5 months (95% CI: 10.73-22.27). Exploratory analysis highlighted that patients who were intolerant to previous immune-related regimens (17 patients) might have a superior prognosis (median OS: 22.3 months vs 12.5 months, P=0.024). Additionally, adverse reactions with any grades during anlotinib plus PD-1 blockades administration were observed in 62 patients (92.5%), of which 31 patients (46.3%) had ≥grade 3 adverse reactions. Most common adverse reactions were fatigue, hypertension, diarrhea and hepatotoxicity. Conclusion: Anlotinib plus PD-1 blockades demonstrated promising effectiveness and tolerable safety in patients with previously immunotherapy treated advanced NSCLC. Those who were intolerant to previous immune-related regimens might benefit significantly from treatment with anlotinib plus PD-1 blockades. This conclusion should be confirmed in future studies.

Biosynthetic potential of uncultured anammox community bacteria revealed through multi-omics analysis.

Microbial secondary metabolites (SMs) and their derivatives have been widely used in medicine, agriculture, and energy. Growing needs for renewable energy and the challenges posed by antibiotic resistance, cancer, and pesticides emphasize the crucial hunt for new SMs. Anaerobic ammonium-oxidation (anammox) systems harbor many uncultured or underexplored bacteria, representing potential resources for discovering novel SMs. Leveraging HiFi long-read metagenomic sequencing, 1,040 biosynthetic gene clusters (BGCs) were unearthed from the anammox microbiome with 58% being complete and showcasing rich diversity. Most of them showed distant relations to known BGCs, implying novelty. Members of the underexplored lineages (Chloroflexota and Planctomycetota) and Proteobacteria contained lots of BGCs, showcasing substantial biosynthetic potential. Metaproteomic results indicated that Planctomycetota members harbored the most active BGCs, particularly those involved in producing potential biofuel-ladderane. Overall, these findings underscore that anammox microbiomes could serve as valuable resources for mining novel BGCs and discovering new SMs for practical application.

Role of deubiquitinase JOSD2 in the pathogenesis of esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with limited treatment options. Deubiquitinases (DUBs) have been confirmed to play a crucial role in the development of malignant tumors. JOSD2 is a DUB involved in controlling protein deubiquitination and influencing critical cellular processes in cancer. AIM: To investigate the impact of JOSD2 on the progression of ESCC. METHODS: Bioinformatic analyses were employed to explore the expression, prognosis, and enriched pathways associated with JOSD2 in ESCC. Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines (KYSE30 and KYSE150). Functional assays, including cell proliferation, colony formation, drug sensitivity, migration, and invasion, were performed, revealing the impact of JOSD2 on ESCC cell lines. JOSD2's role in xenograft tumor growth and drug sensitivity in vivo was also assessed. The proteins that interacted with JOSD2 were identified using mass spectrometry. RESULTS: Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues, which was associated with poor prognosis. Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells. JOSD2 knockdown inhibited ESCC cell activity, including proliferation and colony-forming ability. Moreover, JOSD2 knockdown decreased the drug resistance and migration of ESCC cells, while JOSD2 overexpression enhanced these phenotypes. In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC. Mechanistically, JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways. Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2, which identified the four primary proteins that bind to JOSD2, namely USP47, IGKV2D-29, HSP90AB1, and PRMT5. CONCLUSION: JOSD2 plays a crucial role in enhancing the proliferation, migration, and drug resistance of ESCC, suggesting that JOSD2 is a potential therapeutic target in ESCC.

Effects of the Glucocorticoid-Mediated Mitochondrial Translocation of Glucocorticoid Receptors on Oxidative Stress and Pyroptosis in BV-2 Microglia.

Microglia are resident macrophages within the central nervous system, serving as the first responders to neuroinflammation. Glucocorticoids (GCs) may cause damage to brain tissue, but the specific mechanism remains unclear. This study was divided into two parts: a glucocorticoid receptor (GR) mitochondrial translocation intervention experiment and a mitochondrial oxidative stress inhibition experiment. BV-2 microglia were stimulated with dexamethasone (DEX) and treated with either tubastatin-A or mitoquinone (MitoQ) for 24 h. Our results showed that DEX increased the translocation of GRs to mitochondria, and this effect was accompanied by decreases in the expression of mitochondrially encoded cytochrome c oxidase 1 (MT-CO1) and mitochondrially encoded cytochrome c oxidase 3 (MT-CO3) and increases in the expression of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3), caspase-1, and Gasdermin D (GSDMD). The level of mitochondrial respiratory chain complex IV (MRCC IV) and adenosine triphosphate (ATP) was decreased. An elevation in the level of mitochondrial oxidative stress and the opening of the mitochondrial permeability transition pore (mPTP) was also observed. Mechanistically, tubastatin-A significantly suppressed the mitochondrial translocation of GRs, improved the expression of mitochondrial genes, promoted the restoration of mitochondrial function, and inhibited pyroptosis. MitoQ significantly prevented mitochondrial oxidative stress, improved mitochondrial function, and reduced apoptosis and pyroptosis. Both tubastatin-A and MitoQ suppressed DEX-induced pyroptosis. This study substantiates that the increase in the mitochondrial translocation of GRs mediated by GCs exacerbates oxidative stress and pyroptosis in microglia, which indicates that the regulation of mitochondrial pathways by GCs is pathogenic to microglia.

Glial Cell Activation and Immune Responses in Glaucoma: A Systematic Review of Human Postmortem Studies of the Retina and Optic Nerve.

Although researched extensively the understanding regarding mechanisms underlying glaucoma pathogenesis remains limited. Further, the exact mechanism behind neuronal death remains elusive. The role of neuroinflammation in retinal ganglion cell (RGC) death has been prominently theorised. This review provides a comprehensive summary of neuroinflammatory responses in glaucoma. A systematic search of Medline and Embase for articles published up to 8th March 2023 yielded 32 studies using post-mortem tissues from glaucoma patients. The raw data were extracted from tables and text to calculate the standardized mean differences (SMDs). These studies utilized post-mortem tissues from glaucoma patients, totalling 490 samples, compared with 380 control samples. Among the included studies, 27 reported glial cell activation based on changes to cellular morphology and molecular staining. Molecular changes were predominantly attributed to astrocytes (62.5%) and microglia (15.6%), with some involvement of Muller cells. These glial cell changes included amoeboid microglial cells with increased CD45 or HLA-DR intensity and hypertrophied astrocytes with increased glial fibrillary acidic protein labelling. Further, changes to extracellular matrix proteins like collagen, galectin, and tenascin-C suggested glial cells' influence on structural changes in the optic nerve head. The activation of DAMPs-driven immune response and the classical complement cascade was reported and found to be associated with activated glial cells in glaucomatous tissue. Increased pro-inflammatory markers such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were also linked to glial cells. Glial cell activation was also associated with mitochondrial, vascular, metabolic and antioxidant component disruptions. Association of the activated glial cells with pro-inflammatory responses, dysregulation of homeostatic components and antigen presentation indicates that glial cell responses influence glaucoma progression. However, the exact mechanism triggering these responses and underlying interactions remains unexplored. This necessitates further research using human samples for an increased understanding of the precise role of neuroinflammation in glaucoma progression.

Neutrophil­to­lymphocyte ratio reflects lung injury in thoracic radiotherapy and immune checkpoint inhibitors combination therapy with different sequences.

The combination of thoracic radiotherapy and immune checkpoint inhibitors (ICIs) has emerged as a novel treatment approach for malignant tumors. However, it is important to consider the potential exacerbation of lung injury associated with this treatment modality. The neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, holds promise as a non-invasive indicator for assessing the toxicity of this combination therapy. To investigate this further, a study involving 80 patients who underwent thoracic radiotherapy in conjunction with ICIs was conducted. These patients were divided into two groups: The concurrent therapy group and the sequential therapy group. A logistic regression analysis was conducted to ascertain risk factors for grade ≥2 pneumonitis. Following propensity score matching, the NLR values were examined between the concurrent group and the sequential group to evaluate any disparity. A mouse model of radiation pneumonitis was established, and ICIs were administered at varying time points. The morphological evaluation of lung injury was conducted using H&E staining, while the NLR values of peripheral blood were detected through flow cytometry. Logistic regression analysis revealed that radiation dosimetric parameters (mean lung dose, total dose and V20), the inflammatory index NLR at the onset of pneumonitis, and treatment sequences (concurrent or sequential) were identified as independent predictors of grade ≥2 treatment-related pneumonitis. The results of the morphological evaluation indicated that the severity of lung tissue injury was greater in cases where programmed cell death protein 1 (PD-1) blockade was administered during thoracic radiotherapy, compared with cases where PD-1 blockade was administered 14 days after radiotherapy. Moreover, the present study demonstrated that the non-invasive indicator known as the NLR has the potential to accurately reflect the aforementioned injury.

Inhibition of anlotinib-induced autophagy attenuates invasion and migration by regulating epithelial-mesenchymal transition and cytoskeletal rearrangement through ATG5 in human osteosarcoma cells.

The cure rates for osteosarcoma have remained unchanged in the past three decades, especially for patients with pulmonary metastasis. Thus, a new and effective treatment for metastatic osteosarcoma is urgently needed. Anlotinib has been reported to have antitumor effects on advanced osteosarcoma. However, both the effect of anlotinib on autophagy in osteosarcoma and the mechanism of anlotinib-mediated autophagy in pulmonary metastasis are unclear. The effect of anlotinib treatment on the metastasis of osteosarcoma was investigated by transwell assays, wound healing assays, and animal experiments. Related proteins were detected by western blotting after anlotinib treatment, ATG5 silencing, or ATG5 overexpression. Immunofluorescence staining and transmission electron microscopy were used to detect alterations in autophagy and the cytoskeleton. Anlotinib inhibited the migration and invasion of osteosarcoma cells but promoted autophagy and increased ATG5 expression. Furthermore, the decreases in invasion and migration induced by anlotinib treatment were enhanced by ATG5 silencing. In addition, Y-27632 inhibited cytoskeletal rearrangement, which was rescued by ATG5 overexpression. ATG5 overexpression enhanced epithelial-mesenchymal transition (EMT). Mechanistically, anlotinib-induced autophagy promoted migration and invasion by activating EMT and cytoskeletal rearrangement through ATG5 both in vitro and in vivo. Our results demonstrated that anlotinib can induce protective autophagy in osteosarcoma cells and that inhibition of anlotinib-induced autophagy enhanced the inhibitory effects of anlotinib on osteosarcoma metastasis. Thus, the therapeutic effect of anlotinib treatment can be improved by combination treatment with autophagy inhibitors, which provides a new direction for the treatment of metastatic osteosarcoma.

Accuracy of an Artificial Intelligence Chatbot's Interpretation of Clinical Ophthalmic Images.

Importance: Ophthalmology is reliant on effective interpretation of multimodal imaging to ensure diagnostic accuracy. The new ability of ChatGPT-4 (OpenAI) to interpret ophthalmic images has not yet been explored. Objective: To evaluate the performance of the novel release of an artificial intelligence chatbot that is capable of processing imaging data. Design, Setting, and Participants: This cross-sectional study used a publicly available dataset of ophthalmic cases from OCTCases, a medical education platform based out of the Department of Ophthalmology and Vision Sciences at the University of Toronto, with accompanying clinical multimodal imaging and multiple-choice questions. Across 137 available cases, 136 contained multiple-choice questions (99%). Exposures: The chatbot answered questions requiring multimodal input from October 16 to October 23, 2023. Main Outcomes and Measures: The primary outcome was the accuracy of the chatbot in answering multiple-choice questions pertaining to image recognition in ophthalmic cases, measured as the proportion of correct responses. χ2 Tests were conducted to compare the proportion of correct responses across different ophthalmic subspecialties. Results: A total of 429 multiple-choice questions from 136 ophthalmic cases and 448 images were included in the analysis. The chatbot answered 299 of multiple-choice questions correctly across all cases (70%). The chatbot's performance was better on retina questions than neuro-ophthalmology questions (77% vs 58%; difference = 18%; 95% CI, 7.5%-29.4%; χ21 = 11.4; P < .001). The chatbot achieved a better performance on nonimage-based questions compared with image-based questions (82% vs 65%; difference = 17%; 95% CI, 7.8%-25.1%; χ21 = 12.2; P < .001).The chatbot performed best on questions in the retina category (77% correct) and poorest in the neuro-ophthalmology category (58% correct). The chatbot demonstrated intermediate performance on questions from the ocular oncology (72% correct), pediatric ophthalmology (68% correct), uveitis (67% correct), and glaucoma (61% correct) categories. Conclusions and Relevance: In this study, the recent version of the chatbot accurately responded to approximately two-thirds of multiple-choice questions pertaining to ophthalmic cases based on imaging interpretation. The multimodal chatbot performed better on questions that did not rely on the interpretation of imaging modalities. As the use of multimodal chatbots becomes increasingly widespread, it is imperative to stress their appropriate integration within medical contexts.