[Study on the inhibitory and pro-apoptotic effects of different concentrations of total tanshinone alone and in combination with tyrosine kinase inhibitors on human myeloid leukemia cell lines].

Objective: To explore the effect and investigate the molecular mechanism of different concentrations of total tanshinones alone and in combination with tyrosine kinase inhibitors (TKIs) on the proliferation inhibition and apoptosis of human myeloid leukemia cell lines. Methods: K562 and Kasumi-1 cell lines were purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences, and the TKIs-resistant strain K562/T315I cell line was constructed in Molecular Medicine Research Center, Beijing Lu Daopei Institute of Hematology. Logarithmic growth phase cells were taken and divided into intervention groups with total tanshinone of 0, 2.19, 4.38, 8.75, 17.50 and 35.00 µg/ml intervention groups, which were inoculated in 96-well plates at a density of 1×104 cells/well and exposed to the drug for 24 h, and a control group treated with dimethyl sulfoxide was also set up simultaneously. All experiments were repeated independently 3-5 times. The proliferative activity of the cells was assessed using the CCK-8 assay, the apoptotic rates were measured by flow cytometry, and the expression levels of apoptosis-regulating proteins Bcl-2 and Bax were analyzed by Western blotting. The cell lines treated and untreated with total tanshinone were subjected to transcriptome sequencing and gene set enrichment analysis to identify differentially expressed genes. Results: The half-inhibitory concentration (IC50) values of 8.75 µg/ml total tanshinone at 24 h for K562, K562/T315I and Kasumi-1 cells were (4.11±0.02), (4.95±0.04) and (3.98±0.01) µg/ml, respectively. When combined with 0.25 µmol/L imatinib, 8.75 µg/ml total tanshinone could enhance the induction of apoptosis effects on K562 and K562/T315I cell lines. After being treated with 4.38, 8.75, and 17.50 µg/ml of total tanshinone for 24 h, compared with the control group, total tanshinone upregulated the expression level of Bax protein, downregulated the expression level of Bcl-2 protein, and decreased the Bcl-2/Bax ratio (all P<0.05). Total tanshinone inhibited the proliferation-related signaling pathway and DNA damage repair pathway of myeloid leukemia cell lines, and activated the signaling pathway that induces apoptosis in leukemia cells. Conclusion: Different concentrations of total tanshinoneinhibites proliferation and promote apoptosis in K562, Kasumi-1 and TKIs-resistant K562/T315I cell lines, and further enhance the anti-leukemic effect when combined with TKIs.

[Dynamic monitoring and esthetic evaluation of dimensional changes in the peri-implant soft tissue contour after the immediate implant placement and provisionalization with the modified socket-shield technique in the esthetic zone].

Objective: To accurately measure the dynamic changes of peri-implant soft tissue within one year after the immediate implant placement and provisionalization with the modified socket-shield technique (MSST) in the esthetic zone, and to provide a basis for evaluating the effect of the modified socket-shield technique on the maintenance of peri-implant soft tissue. Methods: A total of 22 patients (22 implants) were prospectively included 1 year after completion of immediate implant placement and provisionalization (IIPP) within MSST in the esthetic zone from January 2022 to January 2024 at the Department of Oral Implantology in the Stomatological Hospital of Chongqing Medical University. The patients were (40±13) years old (21-75 years), including 9 males and 13 females. The intraoral optical models of patients were obtained by an intraoral scanner system preoperatively and at 3, 6, and 12 months postoperatively, respectively. The standard tessellation language files of intraoral optical models at multiple time points were imported to Geomagic Studio 2013 to be superimposed and aligned for analyzing the peri-implant soft tissue contour on the labial side of the implant site at multiple levels. The amount of gingival margin recession, gingival papilla change, and thickness change of the labial side of the soft tissues at each postoperative point in time were measured at each postoperative time point, as well as evaluating the esthetic effect by the pink esthetic score (PES). Results: No adverse events occurred in all the implants during the 12-month follow-up period. The recession level of the gingival margin of the implant site (GL) was 0.08 (0.07) mm, the recession level of the mesial papilla (ML) was 0.19 (0.25) mm, and the recession level of the distal papilla (DL) was 0.19 (0.10) mm. The average collapse thickness of the soft tissue contour on the labial side of the implant (ΔD) was (0.39±0.09) mm, mainly occurring within 2 mm of the root of the gingival margin. The height of the alveolar bone was reduced by (0.17±0.08) mm. The thickness of the labial alveolar bone at 1, 3, and 5 mm root side of the implant shoulder was reduced by (0.13±0.08), (0.12±0.10) and 0.04 (0.17) mm, respectively. The postoperative pink esthetic score was 13.00 (2.25) points at 12 months, which suggested that all implant sites achieved ideal esthetic results. Conclusions: The labial soft tissue contour at implant sites shows minimal change following immediate implant placement and provisionalization using the modified socket-shield technique for 1 year in the esthetic zone.

Liquid foam improves potency and safety of gene therapy vectors.

Interest in gene therapy medicines is intensifying as the first wave of gene-correcting drugs is now reaching patient populations. However, efficacy and safety concerns, laborious manufacturing protocols, and the high cost of the therapeutics are still significant barriers in gene therapy. Here we describe liquid foam as a vehicle for gene delivery. We demonstrate that embedding gene therapy vectors (nonviral or viral) in a methylcellulose/xanthan gum-based foam formulation substantially boosts gene transfection efficiencies in situ, compared to liquid-based gene delivery. We further establish that our gene therapy foam is nontoxic and retained at the intended target tissue, thus minimizing both systemic exposure and targeting of irrelevant cell types. The foam can be applied locally or injected to fill body cavities so the vector is uniformly dispersed over a large surface area. Our technology may provide a safe, facile and broadly applicable option in a variety of clinical settings.

Gut microbiome and symptoms in females with irritable bowel syndrome: a cross-sectional analysis.

Irritable bowel syndrome (IBS), a disorder of gut-brain interaction, is associated with abdominal pain and stool frequency/character alterations that are linked to changes in microbiome composition. We tested whether taxa differentially abundant between females with IBS vs healthy control females (HC) are associated with daily gastrointestinal and psychological symptom severity. Participants (age 18-50 year) completed a 3-day food record and collected a stool sample during the follicular phase. They also completed a 28-day diary rating symptom intensity; analysis focused on the three days after the stool sample collection. 16S rRNA gene sequencing was used for bacterial identification. Taxon abundance was compared between IBS and HC using zero-inflated quantile analysis (ZINQ). We found that females with IBS (n = 67) had greater Bacteroides abundance (q = 0.003) and lower odds of Bifidobacterium presence (q = 0.036) compared to HC (n = 46) after adjusting for age, race, body mass index, fibre intake, and hormonal contraception use. Intestimonas, Oscillibacter, and Phascolarctobacterium were more often present and Christensenellaceae R-7 group, Collinsella, Coprococcus 2, Moryella, Prevotella 9, Ruminococcaceae UCG-002, Ruminococcaceae UCG-005, and Ruminococcaceae UCG-014 were less commonly present in IBS compared to HC. Despite multiple taxon differences in IBS vs HC, we found no significant associations between taxon presence or abundance and average daily symptom severity within the IBS group. This may indicate the need to account for interactions between microbiome, dietary intake, metabolites, and host factors.

[The relationship between the comprehensive blood inflammation indexes and stage I pneumoconiosis and its combined lung infections].

Objective: To analyze the comprehensive blood inflammation index of the patients with stage I pneumoconiosis complicated with pulmonary infection, and to explore its value in predicting the patients' disease. Methods: In September 2023, 83 patients with stage I pneumoconiosis who were treated in Tianjin Occupational Diseases Precaution and Therapeutic Hospital from November 2021 to August 2023 were selected and divided into non-infected group (56 cases) and infected group (27 cases) according to whether they were combined with lung infection. Workers with a history of dust exposure but diagnosed without pneumoconiosis during the same period were selected as the control group (65 cases) . By referring to medical records and collecting clinical data such as gender, age, occupational history, past medical history, hematology testing, the differences in the comprehensive blood inflammation indexes among the three groups were compared, ROC curve was drawn, and the relationship between comprehensive blood inflammation indexes and stage I pneumoconiosis and its combined lung infection was analyzed. Results: There were significtant differences in the number of neutrophils (N) , the number of lymphocytes (L) , the number of monocytes (M) , C-reactive protein (CRP) , the neutrophil to lymphocyte ratio (NLR) , the monocyte to lymphocyte ratio (MLR) , the platelet to lymphocyte ratio (PLR) , the systemic immune-inflammatory index (SII) , the systemic inflammation response index (SIRI) , the aggregate index of systemic inflammation (AISI) , the derived neutrophil to lymphocyte ratio (dNLR) , the neutrophil to lymphocyte and platelet ratio (NLPR) , and the C-reactive protein to lymphocyte ratio (CLR) (P<0.05) . Compared with the control group, MLR, SIRI and AISI in the non-infected group were significantly increased (P<0.05) . NLR, MLR, PLR, SII, SIRI, AISI, dNLR, NLPR, CLR were significantly increased (P<0.05) . Compared with the non-infected group, NLR, PLR, SII, SIRI, AISI, dNLR, NLPR and CLR were significantly increased in the infected group (P<0.05) . ROC analysis showed that NLR, MLR, PLR, SII, SIRI and AISI had a certain predictive capability for stage I pneumoconiosis (P<0.05) , among which MLR had the highest efficacy, with an AUC of 0.791 (95% CI: 0.710-0.873) , the cut-off value was 0.18, the sensitivity was 71.4%, and the specificity was 78.5%. NLR, MLR, PLR, SII, SIRI, AISI, dNLR, NLPR and CLR all had a certain predictive capability forstage I pneumoconiosis combined lung infection (P<0.05) , among which CLR had the highest efficacy, with an AUC of 0.904 (95%CI: 0.824~0.985) , the cut-off value was 5.33, sensitivity was 77.8%, specificity was 98.2%. Conclusion: The comprehensive blood inflammation index may be an auxiliary predictor of stage I pneumoconiosis and its combined lung infections.

[The influence of knocking down the expression of low-density lipoprotein receptor associated proteins on the vascular abnormalities in hepatocellular carcinoma and its mechanisms].

Objectives: To investigate the effect of the expression of low-density lipoprotein receptor associated protein (LDLR) on the vascular abnormalities in hepatocellular carcinoma (HCC) and its mechanisms. Methods: Based on the information of Oncomine Cancer GeneChip database, we analyzed the correlation between the expression level of LDLR and the expression level of carcinoembryonic antigen (CEA) and CD31 in hepatocellular carcinoma tissues. Lentiviral transfection of short hairpin RNA target genes was used to construct LDLR-knockdown MHCC-97H and HLE hepatocellular carcinoma cells. The differential genes and their expression level changes in LDLR-knockdown hepatocellular carcinoma cells were detected by transcriptome sequencing, real-time fluorescence quantitative polymerase chain reaction, and protein immunoblotting. The gene-related signaling pathways that involve LDLR were clarified by enrichment analysis. The effect of LDLR on CEA was assessed by the detection of CEA content in conditioned medium of hepatocellular carcinoma cells. Angiogenesis assay was used to detect the effect of LDLR on the angiogenic capacity of human umbilical vein endothelial cells, as well as the role of CEA in the regulation of angiogenesis by LDLR. Immunohistochemical staining was used to detect the expression levels of LDLR in 176 hepatocellular carcinoma tissues, and CEA and CD31 in 146 hepatocellular carcinoma tissues, and analyze the correlations between the expression levels of LDLR, CEA, and CD31 in the tissues, serum CEA, and alanine transaminase (ALT). Results: Oncomine database analysis showed that the expressions of LDLR and CEA in the tissues of hepatocellular carcinoma patients with portal vein metastasis were negatively correlated (r=-0.64, P=0.001), whereas the expressions of CEA and CD31 in these tissues were positively correlated ( r=0.46, P=0.010). The transcriptome sequencing results showed that there were a total of 1 032 differentially expressed genes in the LDLR-knockdown group and the control group of MHCC-97H cells, of which 517 genes were up-regulated and 515 genes were down-regulated. The transcript expression level of CEACAM5 was significantly up-regulated in the cells of the LDLR-knockdown group. The Gene Ontology (GO) function enrichment analysis showed that the differential genes were most obviously enriched in the angiogenesis function. The Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis showed that the relevant pathways involved mainly included the cellular adhesion patch, the extracellular matrix receptor interactions, and the interactions with the extracellular matrix receptors. The CEA content in the conditioned medium of the LDLR-knockdown group was 43.75±8.43, which was higher than that of the control group (1.15±0.14, P＜0.001). The results of angiogenesis experiments showed that at 5 h, the number of main junctions, the number of main segments, and the total area of the lattice formed by HUVEC cells cultured with the conditioned medium of MHCC-97H cells in the LDLR-knockdown group were 295.3±26.4, 552.5±63.8, and 2 239 781.0±13 8211.9 square pixels, which were higher than those of the control group (113.3±23.5, 194.8±36.5, and 660 621.0±280 328.3 square pixels, respectively, all P＜0.01).The number of vascular major junctions, the number of major segments, and the total area of the lattice formed by HUVEC cells cultured in conditioned medium with HLE cells in the LDLR-knockdown group were 245.3±42.4, 257.5±20.4, and 2 535 754.5±249 094.2 square pixels, respectively, which were all higher than those of the control group (113.3±23.5, 114.3±12.2, and 1 565 456.5±219 259.7 square pixels, respectively, all P＜0.01). In the conditioned medium for the control group of MHCC-97H cells,the number of main junctions, the number of main segments, and the total area of the lattice formed by the addition of CEA to cultured HUVEC cells were 178.9±12.0, 286.9±12.3, and 1 966 990.0±126 249.5 spixels, which were higher than those in the control group (119.7±22.1, 202.7±33.7, and 1 421 191.0±189 837.8 square pixels, respectively). The expression of LDLR in hepatocellular carcinoma tissues was not correlated with the expression of CEA, but was negatively correlated with the expression of CD31 (r=-0.167, P=0.044), the level of serum CEA (r=-0.061, P=0.032), and the level of serum ALT(r=-0.147,P=0.05). The expression of CEA in hepatocellular carcinoma tissues was positively correlated with the expression of CD31 (r=0.192, P=0.020). The level of serum CEA was positively correlated with the level of serum ALT (r=0.164, P=0.029). Conclusion: Knocking down LDLR can promote vascular abnormalities in HCC by releasing CEA.

Small extracellular vesicles facilitate epithelial-mesenchymal transition in chronic rhinosinusitis with nasal polyps via the miR-375-3p/QKI axis.

BACKGROUND: Epithelial-mesenchymal transition (EMT) plays a crucial role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the involvement of small extracellular vesicles (sEVs) in EMT and their contributions to CRSwNP has not been extensively investigated. METHODS: SEVs were isolated from nasal mucosa through ultracentrifugation. MicroRNA sequencing and reverse-transcription quantitative polymerase chain reaction were employed to analyze the differential expression of microRNAs carried by sEVs. Human nasal epithelial cells (hNECs) were used to assess the EMT-inducing effect of sEVs/microRNAs. EMT-associated markers were detected by western blotting and immunofluorescence. Dual-luciferase reporter assay was performed to determine the target gene of miR-375-3p. MicroRNA mimic, lentiviral, and plasmid transduction were used for functional experiments. RESULTS: In line with the greater EMT status in eosinophilic CRSwNP (ENP), sEVs derived from ENP (ENP-sEVs) could induce EMT in hNECs. MiR-375-3p was elevated in ENP-sEVs compared to that in control and nonENP. MiR-375- 3p carried by ENP-sEVs facilitated EMT by directly targeting KH domain containing RNA binding (QKI) at seed sequences of 913-919, 1025-1033, and 2438-2444 in 3'-untranslated region. Inhibition of QKI by miR-375-3p overexpression promoted EMT, which could be reversed by restoration of QKI. Furthermore, the abundance of miR-375-3p in sEVs was closely correlated with the clinical symptom score and disease severity. CONCLUSIONS: MiR-375-3p-enriched sEVs facilitated EMT by suppressing QKI in hNECs. The association of miR-375-3p with disease severity underscores its potential as both a diagnostic marker and a therapeutic target for the innovative management of CRSwNP.

[Endoscopic response evaluation in gastrointestinal cancers after neoadjuvant chemora- diotherapy].

Neoadjuvant chemoradiotherapy has emerged as the standard treatment for locally advanced rectal cancer, esophageal cancer and gastroesophageal junction cancer which can not only improve the rate of local control but also induce pathological complete response in some patients. For patients who have achieved clinical complete response after neoadjuvant therapy, the watch & wait strategy and organ preservation could reduce unnecessary surgery and minimize the risk of postoperative complications, meanwhile greatly improve patients' quality of life without affecting the oncologic outcome. At present, a variety of methods, including white light endoscopy, endoscopic forceps biopsy, image enhanced endoscopy, endoscopic ultrasound, endoscopic ultrasound guided fine needle aspiration, endoscopic submucosal dissection, artificial intelligence assisted technology, etc., have become important assistance for the evaluation of tumor response after neoadjuvant chemoradiotherapy and have been widely used in clinical practice. This review will briefly introduce the application of the endoscopic approaches mentioned above and some novel endoscopic techniques and developing trends in response evaluation for patients with locally advanced rectal cancer, esophageal cancer and gastroesophageal junction cancer patients receiving neoadjuvant chemoradiotherapy.

AAPM Task Group 334: A guidance document to using radiotherapy immobilization devices and accessories in an MR environment.

Use of magnetic resonance (MR) imaging in radiation therapy has increased substantially in recent years as more radiotherapy centers are having MR simulators installed, requesting more time on clinical diagnostic MR systems, or even treating with combination MR linear accelerator (MR-linac) systems. With this increased use, to ensure the most accurate integration of images into radiotherapy (RT), RT immobilization devices and accessories must be able to be used safely in the MR environment and produce minimal perturbations. The determination of the safety profile and considerations often falls to the medical physicist or other support staff members who at a minimum should be a Level 2 personnel as per the ACR. The purpose of this guidance document will be to help guide the user in making determinations on MR Safety labeling (i.e., MR Safe, Conditional, or Unsafe) including standard testing, and verification of image quality, when using RT immobilization devices and accessories in an MR environment.

Efficacy evaluation of Mongolian medical warm acupuncture for sciatica caused by lumbar disc herniation: a randomized, controlled, single-blind clinical trial.

OBJECTIVE: This study aimed to evaluate the short-term and long-term efficacy of Mongolian medical warm acupuncture for sciatica caused by lumbar disc herniation (LDH). PATIENTS AND METHODS: The patients diagnosed with sciatica caused by LDH were randomly divided into the warm acupuncture of the Mongolian medicine group (n = 42, warm acupuncture treatment), the sham acupuncture group (n = 38, sham acupuncture using blunt-tipped needles) and the conventional drug group (n = 40, ibuprofen sustained release capsule). All patients were treated for 4 weeks and followed up for 8 weeks. The visual analog scale for leg pain (VAS-LP), Mongolian medicine indicators (efficacy indicators), VAS for waist pain (VAS-WP) and the Mos 36-item short form health survey (SF-36) score were analyzed at baseline, after two-week treatment, after four-week treatment, at four-week follow-up and at eight-week follow-up. RESULTS: Warm acupuncture treatment significantly decreased the VAS-LP and VAS-WP scores of patients at treatment and follow-up (p < 0.05), and pain was improved compared to the conventional drug group and sham acupuncture group. The total effective rate was markedly higher in the warm acupuncture of the Mongolian medicine group compared with the conventional drug group at 8-week follow-up (p < 0.05), but sham acupuncture treatment resulted in no evident improvement in the Mongolian medicine indicators. Additionally, at treatment and follow-up, warm acupuncture of the Mongolian medicine group showed a significant increase in the physical function, physical role, body pain, and emotional and mental health role scores of the SF-36 survey compared with the sham acupuncture groups. CONCLUSIONS: Mongolian medical warm acupuncture effectively relieves leg and waist pain and improves the total therapeutic effect and the quality of daily life for patients with sciatica caused by LDH, with significant long-term efficacy. Our study provides a basis for warm acupuncture in the treatment of sciatica caused by LDH. Chinese Clinical Trial Registry ID: ChiCTR- INR-15007413.

[Research progress on neurotoxicity induced by metal pollutants through astrocytes].

Metal pollutants in the natural environment and industrial environment can enter organisms through the respiratory tract and digestive tract causing adverse health effects. Many kinds of literatures confirm that metal pollutants have neurotoxicity. Recent studies have showed that astrocytes play an important role in neurotoxicity induced by metal pollutants. In this review, the latest progress of neurotoxicity induced by lead, mercury, cadmium, antimony and copper through astrocytes in recent years is summarized, which provides a new clue for the neurotoxicity research of metal pollutants.

[A survey on the current situation of serum vitamin A and vitamin D levels among children aged 2-<7 years of 20 cities in China].

Objective: To investigate serum vitamin A and vitamin D status in children aged 2-<7 years in 20 cities in China. Methods: A cross-sectional study was conducted. A total of 2 924 healthy children aged 2-<7 years were recruited from September 2018 to September 2019 from 20 cities in China, categorized by age groups of 2-<3 years, 3-<5 years, and 5-<7 years. The demographic and economic characteristics and health-related information of the enrolled children were investigated. Body weight and height were measured by professional staff members. The serum vitamin A and vitamin D levels were detected by high-performance liquid chromatography-tandem mass spectrometry. Chi-square test and Logistic regression were applied to analyze the association between vitamin A and vitamin D deficiency and insufficiency as well as their underlying impact factors. Results: The age of the 2 924 enrolled children was 4.33 (3.42, 5.17) years. There were 1 726 males (59.03%) and 1 198 females (40.97%). The prevalences of vitamin A and vitamin D deficiency in enrolled children were 2.19% (64/2 924) and 3.52% (103/2 924), respectively, and the insufficiency rates were 29.27% (856/2 924) and 22.20% (649/2 924), respectively. Children with both vitamin A and vitamin D deficiencies or insufficiencies were found in 10.50% (307/2 924) of cases. Both vitamin A (χ2=7.91 and 8.06, both P=0.005) and vitamin D (χ2=71.35 and 115.10, both P<0.001) insufficiency rates were higher in children aged 3-<5 and 5-<7 years than those in children aged 2-<3 years. Vitamin A and vitamin D supplementation in the last 3 months was a protective factor for vitamin A and D deficiency and insufficiency, respectively (OR=0.68 and 0.22, 95%CI 0.49-0.95 and 0.13-0.40, both P<0.05). The rates of vitamin A and D insufficiency was higher in children with annual household incomes <60 000 RMB than in those with annual household incomes ≥60 000 RMB (χ2=34.11 and 10.43, both P<0.01). Northwest and Southwest had the highest rates of vitamin A and vitamin D insufficiency in children aged 2-<7 yeas, respectively (χ2=93.22 and 202.54, both P<0.001). Conclusions: Among 20 cities in China, children aged 2-<7 years experience high rates of vitamin A and vitamin D insufficiency, which are affected by age, family economic level, vitamin A and vitamin D supplementation, and regional economic level. The current results suggest that high level of attention should be paid to vitamin A and vitamin D nutritional status of preschool children.

[Research advances on application of sub-epidermal moisture scanner in monitoring tissue viability of early pressure injuries].

Pressure injury (PI) not only reduces the quality of life of patients but also is expensive to manage, placing a heavy financial burden on patients and their families, and society. Despite the increasing diversity of methods used to identify early PI, there are still few methods that can truly and accurately predict early PI. The sub-epidermal moisture scanner is the first U.S. Food and Drug Administration-authorized PI management device that can predict the occurrence and development of PI by measuring the level of local tissue bio-capacitance and monitoring the tissue viability. As an emerging diagnostic instrument, the sub-epidermal moisture scanner has already shown great advantages in clinical practice, which can promote the informatization, digitization, and intelligent prevention and management of PI. This paper introduces the pathophysiological mechanism of PI, elucidates the working principle and parameter settings of the sub-epidermal moisture scanner, its clinical application in monitoring tissue viability in early PI, and its limitation, and looks forward to its future development.

NRG Oncology Assessment of Artificial Intelligence Deep Learning-Based Auto-segmentation for Radiation Therapy: Current Developments, Clinical Considerations, and Future Directions.

Deep learning neural networks (DLNN) in Artificial intelligence (AI) have been extensively explored for automatic segmentation in radiotherapy (RT). In contrast to traditional model-based methods, data-driven AI-based models for auto-segmentation have shown high accuracy in early studies in research settings and controlled environment (single institution). Vendor-provided commercial AI models are made available as part of the integrated treatment planning system (TPS) or as a stand-alone tool that provides streamlined workflow interacting with the main TPS. These commercial tools have drawn clinics' attention thanks to their significant benefit in reducing the workload from manual contouring and shortening the duration of treatment planning. However, challenges occur when applying these commercial AI-based segmentation models to diverse clinical scenarios, particularly in uncontrolled environments. Contouring nomenclature and guideline standardization has been the main task undertaken by the NRG Oncology. AI auto-segmentation holds the potential clinical trial participants to reduce interobserver variations, nomenclature non-compliance, and contouring guideline deviations. Meanwhile, trial reviewers could use AI tools to verify contour accuracy and compliance of those submitted datasets. In recognizing the growing clinical utilization and potential of these commercial AI auto-segmentation tools, NRG Oncology has formed a working group to evaluate the clinical utilization and potential of commercial AI auto-segmentation tools. The group will assess in-house and commercially available AI models, evaluation metrics, clinical challenges, and limitations, as well as future developments in addressing these challenges. General recommendations are made in terms of the implementation of these commercial AI models, as well as precautions in recognizing the challenges and limitations.

Risk Factors for Locoregional Recurrence and Distant Metastasis in 143 Patients with Adenoid Cystic Carcinoma of the External Auditory Canal.

AIMS: Adenoid cystic carcinoma (ACC) grows slowly and is characterised by potential recurrence and metastasis to distant organs. This study aimed to evaluate the risk factors for locoregional recurrence (LRR) and distant metastasis in patients with ACC of the external auditory canal (EAC). MATERIALS AND METHODS: Demographic, pathological, therapeutic and survival data of 143 patients with EAC ACC were reviewed in this study. Univariate and multivariate Cox proportional hazard regression analyses were carried out to determine the risk factors for LRR and distant metastasis. Factors associated with overall survival after LRR and distant metastasis were also analysed. RESULTS: During a median follow-up of 49 months, 31 of 143 patients were observed with LRR and 34 developed distant metastasis. Bone invasion and histological subtype were independent risk factors for locoregional recurrence-free survival. T stage and LRR were independent risk factors for distant metastasis-free survival. Salvage surgery and adjuvant radiotherapy or chemoradiotherapy for LRR resulted in better survival, whereas extrapulmonary metastasis and LRR were associated with a higher risk of poor survival after distant metastasis. CONCLUSION: Patients with distant metastases, especially those with LRR, are at significant risk of poor prognosis. Our findings emphasise the importance of long-term regular follow-up and recommend surgical intervention with radiotherapy for recurrent EAC ACC.

Causal relationship between cigarette smoking behaviors and the risk of hernias: a Mendelian randomization study.

PURPOSE: As the global population continues to age, there is a noticeable yearly rise in the incidence of hernias. Simultaneously, smoking, a widespread addictive behavior and a significant contributor to mortality, has evolved into a pervasive public health concern. Existing literature has already established a connection between smoking and an increased risk of postoperative recurrence and postoperative infections following hernia surgery. However, there remains a dearth of research exploring the association between smoking and hernia morbidity. In this study, our objective is to systematically evaluate the causal relationship between cigarette smoking behaviors and hernia morbidity using a Mendelian randomization (MR) approach. METHODS: Hernia-related data were sourced from the FinnGen Biobank database, while cigarette smoking behavior data were gathered from the GWAS and Sequencing Consortium of Alcohol and Nicotine Use. To assess the causal relationship, we employed five methods: the weighted median, the weighted mode the inverse variance weighted (IVW), MR-Egger, and the simple mode. Sensitivity analysis was conducted, incorporating Cochran's Q test, the MR-Egger intercept test, leave-one-out analysis, and funnel plot. The presentation of the causal relationship is expressed as an odds ratio (OR) along with their corresponding 95% confidence intervals (CI). RESULTS: Employing the IVW method as the reference standard, we found that smoking intensity is associated with an increased risk of diaphragmatic hernia (OR = 1.21, 95% CI 1.00-1.46, P = 0.047). These consistent findings were further corroborated by the weighted median and weighted mode methods (OR = 1.26, 95% CI 1.03-1.54, P = 0.026; OR = 1.25, 95% CI 1.02-1.52, P = 0.045). Conversely, when applying the IVW method, we identified no statistically significant causal relationship between smoking age, smoking initiation status, smoking cessation status, and the incidence of hernia. CONCLUSIONS: Our MR study has uncovered genetic evidence linking smoking intensity and the occurrence of diaphragmatic hernia. The risk of developing diaphragmatic hernia rises in tandem with the intensity of smoking. This emphasizes the crucial role of regularly advising patients to cease smoking in clinical settings.

[Association between remnant cholesterol levels and incident diabetic retinopathy in middle-aged and older patients with diabetes].

Objective: To investigate the association between remnant cholesterol (RC) and the risk of diabetic retinopathy (DR) in middle-aged and older individuals with diabetes. Methods: Based on the Shanghai Nicheng Cohort Study database, the data of 1 255 individuals with diabetes aged 55-70 years at baseline (2013-2014) with complete fundus photographs and serum cholesterol data in Nicheng, Shanghai, were analyzed. Multinomial logistic regression models were used to evaluate risk ratios (RRs) and their 95% confidence intervals (CIs) between baseline RC level and incident DR. Results: The median age of the subjects was 61.9 years, and 60.4% were women. After a 4.6-year follow-up, 79 (6.3%) patients developed DR, including 50 (4.0%) mild non-proliferative DR and 29 (2.3%) referable DR (RDR). Multivariable logistic regression showed that each mmol/L increase of RC was associated with a 40% higher risk of RDR (RR=1.40, 95%CI 1.03-1.90). Compared with the lowest tertile of RC (<0.63 mmol/L), the risk of RDR in the highest tertile (≥0.85 mmol/L) increased by 4.59 times (RR=5.59, 95%CI 1.51-20.73). Conclusion: The RC level may help identify individuals at high risk of incident RDR in middle-aged and older Chinese adults with diabetes.

Design and experiments of a compact electrostatic low energy beam transport with a double Einzel-lens for a transportable neutron source.

A transportable, compact, accelerator-based neutron source is under development at Xian Jiaotong University. An electrostatic low energy beam transport (LEBT) structure with a double Einzel-lens setup was adopted due to its short length and low power consumption. It can transport a pulsed proton beam to the radio frequency quadrupole with a required beam current of 15 mA and an energy of 30 keV. We performed detailed structure optimization and beam tracking to achieve beam matching and small emittance growth. In addition, the fast chopper, beam steering, and diagnostic devices are integrated into the LEBT. The fabrication and assembly of the proton injector have been completed, and beam commissioning was carried out to measure the beam current and Twiss parameters. The design strategy, beam simulation, and experimental results are presented and discussed in this paper.