Clinical evaluation of maxillary sinus floor elevation with or without bone grafts: a systematic review and meta-analysis of randomised controlled trials with trial sequential analysis.

Introduction: Our goal was to systematically review the current evidence comparing the relative effectiveness of two maxillary sinus floor elevation (MSFE) approaches (internal and external) without bone grafts with that of conventional/grafted MSFE in patients undergoing implantation in the posterior maxilla. Material and methods: Medical databases (PubMed/Medline, Embase, Web of Science, and Cochrane Library) were searched for randomised controlled trials published between January 1980 and May 2023. A manual search of implant-related journals was also performed. Studies published in English that reported the clinical outcomes of MSFE with or without bone material were included. The risk of bias was assessed using the Cochrane Handbook Risk Assessment Tool. Meta-analyses and trial sequence analyses were performed on the included trials. Meta-regression analysis was performed using pre-selected covariates to account for substantial heterogeneity. The certainty of evidence for clinical outcomes was assessed using GRADEpro GDT online (Guideline Development Tool). Results: Seventeen studies, including 547 sinuses and 696 implants, were pooled for the meta-analysis. The meta-analysis showed no statistically significant difference between MSFE without bone grafts and conventional MSFE in terms of the implant survival rate in the short term (n = 11, I2 = 0%, risk difference (RD): 0.03, 95% confidence intervals (CI): -0.01-0.07, p = 0.17, required information size (RIS) = 307). Although conventional MSFE had a higher endo-sinus bone gain (n = 13, I2 = 89%, weighted mean difference (WMD): -1.24, 95% CI: -1.91- -0.57, p = 0.0003, RIS = 461), this was not a determining factor in implant survival. No difference in perforation (n = 13, I2 = 0%, RD = 0.03, 95% CI: -0.02-0.09, p = 0.99, RIS = 223) and marginal bone loss (n = 4, I2 = 0%, WMD = 0.05, 95% CI: -0.14-0.23, p = 0.62, no RIS) was detected between the two groups using meta-analysis. The pooled results of the implant stability quotient between the two groups were not robust on sensitivity analysis. Because of the limited studies reporting on the visual analogue scale, surgical time, treatment costs, and bone density, qualitative analysis was conducted for these outcomes. Conclusions: This systematic review revealed that both non-graft and grafted MSFE had high implant survival rates. Owing to the moderate strength of the evidence and short-term follow-up, the results should be interpreted with caution.

Dihydroartemisinin-driven TOM70 inhibition leads to mitochondrial destabilization to induce pyroptosis against lung cancer.

Enhancement of malignant cell immunogenicity to relieve immunosuppression of lung cancer microenvironment is essential in lung cancer treatment. In previous study, we have demonstrated that dihydroartemisinin (DHA), a kind of phytopharmaceutical, is effective in inhibiting lung cancer cells and boosting their immunogenicity, while the initial target of DHA's intracellular action is poorly understood. The present in-depth analysis aims to reveal the influence of DHA on the highly expressed TOM70 in the mitochondrial membrane of lung cancer. The affinity of DHA and TOM70 was analyzed by microscale thermophoresis (MST), pronase stability, and thermal stability. The functions and underlying mechanism were investigated using western blots, qRT-PCR, flow cytometry, and rescue experiments. TOM70 inhibition resulted in mtDNA damage and translocation to the cytoplasm from mitochondria due to the disruption of mitochondrial homeostasis. Further ex and in vivo findings also showed that the cGAS/STING/NLRP3 signaling pathway was activated by mtDNA and thereby malignant cells underwent pyroptosis, leading to enhanced immunogenicity of lung cancer cells in the presence of DHA. Nevertheless, DHA-induced mtDNA translocation and cGAS/STING/NLRP3 mobilization were synchronously attenuated when TOM70 was replenished. Finally, DHA was demonstrated to possess potent anti-lung cancer efficacy in vitro and in vivo. Taken together, these data confirm that TOM70 is an important target for DHA to disturb mitochondria homeostasis, which further activates STING and arouses pyroptosis to strengthen immunogenicity against lung cancer thereupon. The present study provides vital clues for phytomedicine-mediated anti-tumor therapy.

Clinical Assessment of Magnetic Resonance Spectroscopy and Diffusion-Weighted Imaging in Diffuse Glioma: Insights Into Histological Grading and IDH Classification.

PURPOSE: To assess the diagnostic utility of clinical magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI) in distinguishing between histological grading and isocitrate dehydrogenase (IDH) classification in adult diffuse gliomas. METHODS: A retrospective analysis was conducted on 247 patients diagnosed with adult diffuse glioma. Experienced radiologists evaluated DWI and MRS images. The Kruskal-Wallis test examined differences in DWI and MRS-related parameters across histological grades, while the Mann-Whitney U test assessed molecular classification. Receiver Operating Characteristic (ROC) curves evaluated parameter effectiveness. Survival curves, stratified by histological grade and IDH classification, were constructed using the Kaplan-Meier test. RESULTS: The cohort comprised 141 males and 106 females, with ages ranging from 19 to 85 years. The Kruskal-Wallis test revealed significant differences in ADC mean, Cho/NAA, and Cho/Cr concerning glioma histological grade (P < .01). Subsequent application of Dunn's test showed significant differences in ADC mean among each histological grade (P < .01). Notably, Cho/NAA exhibited a marked distinction between grade 2 and grade 3/4 gliomas (P < .01). The Mann-Whitney U test indicated that only ADC mean showed statistical significance for IDH molecular classification (P < .01). ROC curves were constructed to demonstrate the effectiveness of the specified parameters. Survival curves were also delineated to portray survival outcomes categorized by histological grade and IDH classification. Conclusions: Clinical MRS demonstrates efficacy in glioma histological grading but faces challenges in IDH classification. Clinical DWI's ADC mean parameter shows significant distinctions in both histological grade and IDH classification.

Anti-lung cancer synergy of low-dose doxorubicin and PD-L1 blocker co-delivered via mild photothermia-responsive black phosphorus.

We have previously identified a latent interaction mechanism between non-small cell lung cancer cells (NSCLCC) and their associated macrophages (TAM) mediated by mutual paracrine activation of the HMGB1/RAGE/NF-κB signaling. Activation of this mechanism results in TAM stimulation and PD-L1 upregulation in the NSCLCC. In the present work, we found that free DOX at a low concentration that does not cause DNA damage could activate the HMGB1/RAGE/NF-κB/PD-L1 pathway byinducing oxidative stress. It was thus proposed that a combination of low-dose DOX and a PD-L1 blocker delivered in the NSCLC tumor would achieve synergistic TAM stimulation and thereby synergetic anti-tumor potency. To prove this idea, DOX and BMS-202 (a PD-L1 blocker) were loaded to black phosphorus (BP) nanoparticles after dosage titration to yield the BMS-202/DOX@BP composites that rapidly disintegrated and released drug cargo upon mild photothermal heating at 40 °C. In vitro experiments then demonstrated that low-dose DOX and BMS-202 delivered via BMS-202/DOX@BP under mild photothermia displayed enhanced tumor cell toxicity with a potent synergism only in the presence of TAM. This enhanced synergism was due to an anti-tumor M1-like TAM phenotype that was synergistically induced by low dose DOX plus BMS-202 only in the presence of the tumor cells, indicating the damaged tumor cells to be the cardinal contributor to the M1-like TAM stimulation. In vivo, BMS-202/DOX@BP under mild photothermia exhibited targeted delivery to NSCLC graft tumors in mice and synergistic anti-tumor efficacy of delivered DOX and BMS-202. In conclusion, low-dose DOX in combination with a PD-L1 blocker is an effective strategy to turn TAM against their host tumor cells exploiting the HMGB1/RAGE/NF-κB/PD-L1 pathway. The synergetic actions involved highlight the value of TAM and the significance of modulating tumor cell-TAM cross-talk in tumor therapy. Photothermia-responsive BP provides an efficient platform to translate this strategy into targeted, efficacious tumor therapy.

Effect of postoperative intermittent boluses of subcostal quadratus lumborum block on pulmonary function recovery and analgesia after gastrectomy: a randomized controlled clinical trial.

BACKGROUND: Following the gastrectomy, the reduction in pulmonary function is partly attributed to postoperative pain. Subcostal quadratus lumborum block (QLB) has recently emerged as a promising component in multimodal analgesia. We aimed to assess the impact of intermittent boluses of subcostal QLB on pulmonary function recovery and analgesic efficacy after gastrectomy. METHODS: Sixty patients scheduled for gastrectomy were randomly assigned to either control group (multimodal analgesia) or intervention group (intermittent boluses of subcostal QLB plus multimodal analgesia). Two primary outcomes included the preservation of forced expiratory volume in the first second (FEV1) and the pain scores (0-10 cm visual analog score) on coughing 24 h postoperatively. We assessed the pulmonary function parameters, pain score, morphine consumption and number of rescue analgesia at a 24-h interval up to 72 h (Day1, Day2, Day3 respectively) as secondary outcomes. RESULTS: 59 patients were analyzed in a modified intention-to-treat set. The preservation of FEV1 (median difference: 4.0%, 97.5% CI: -5.7 to 14.9, P = 0.332) and pain scores on coughing (mean difference: 0.0 cm, 97.5% CI: -1.1 to 1.2, P = 0.924) did not differ significantly between two groups. In the intervention group, the recovery of forced vital capacity (FVC) was faster 72 h after surgery (interaction effect of group*(Day3-Day0): estimated effect (ß) =0.30 L, standard error (SE) =0.13, P = 0.025), pain scores at rest were lower in the first 3 days (interaction effect of group*(Day1-Day0): ß = - 0.8 cm, SE = 0.4, P = 0.035; interaction effect of group*(Day2-Day0): ß = - 1.0 cm, SE = 0.4, P = 0.014; and interaction effect of group*(Day3-Day0): ß = - 1.0 cm, SE = 0.4, P values = 0.009 respectively), intravenous morphine consumption was lower during 0-24 h (median difference: -3 mg, 95% CI -6 to -1, P = 0.014) and in total 72 h (median difference: -5 mg, 95% CI -10 to -1, P = 0.019), and the numbers of rescue analgesia was fewer during 24-48 h (median difference: 0, 95% CI 0 to 0, P = 0.043). Other outcomes didn't show statistical differences. CONCLUSION: Postoperative intermittent boluses of subcostal QLB did not confer advantages in terms of the preservation of FEV1 or pain scores on coughing 24 h after gastrectomy. However, notable effects were observed in analgesia at rest and FVC recovery.

Ginsenoside Rc alleviates osteoporosis by the TGF-ß/Smad signaling pathway.

Osteoporosis is a common chronic bone disorder in postmenopausal women. Ginsenosides are primary active components in ginseng and the effects of various ginsenoside variants in osteoporosis treatment have been widely revealed. We planned to explore the impact of ginsenoside Rc on bone resorption in an osteoporosis rat model. We used ovariectomized rats to assess the potential impact of ginsenoside Rc on osteoporosis. µ-CT was implemented for analyzing the microstructure of the distal left femur in rats. H&E staining together with Masson staining were applied for bone histomorphometry evaluation. ELISA kits were implemented to detect serum concentrations of TRACP-5b, OCN, CTX, as well as PINP. Ginsenoside Rc treatment lessened the serum levels of TRACP-5b as well as CTX, while increasing serum levels of OCN, and PINP of OVX rats. Moreover, we found that ginsenoside Rc contributed to the synthesis of type I collagen via increasing Col1a1 and Col1a2 levels in femur tissues of ovariectomized rats. Our findings also revealed that ginsenoside Rc activated the TGF-ß/Smad pathway by increasing TGF-ß as well as phosphorylated Smad2/3 protein levels. Ginsenoside Rc alleviates osteoporosis in rats through promoting the TGF-ß/Smad pathway.

p-Smad3 differentially regulates the cytological behavior of osteoclasts before and after osteoblasts maturation.

BACKGROUND: A series of previous investigations have revealed that p-Smad3 plays a facilitative role in the differentiation and maturation of osteoblasts, while also regulating the expression of certain intercellular communication factors. However, the effects of p-Smad3 in osteoblasts before and after maturation on the proliferation, migration, differentiation, apoptosis and other cellular behaviors of osteoclasts have not been reported. METHODS: MC3T3-E1 cells were cultured in osteogenic induction medium for varying durations, After that, the corresponding conditioned medium was collected and the osteoclast lineage cells were treated. To elucidate the regulatory role of p-Smad3 within osteoblasts, we applied the activator TGF-ß1 and inhibitor SIS3 to immature and mature osteoblasts and collected corresponding conditioned media for osteoclast intervention. RESULTS: We observed an elevation of p-Smad3 and Smad3 during the early stage of osteoblast differentiation, followed by a decline in the later stage. we discovered that as osteoblasts mature, their conditioned media inhibit osteoclasts differentiation and the osteoclast-coupled osteogenic effect. However, it promotes apoptosis in osteoclasts and the angiogenesis coupled with osteoclasts. p-Smad3 in immature osteoblasts, through paracrine effects, promotes the migration, differentiation, and osteoclast-coupled osteogenic effects of osteoclast lineage cells. For mature osteoblasts, p-Smad3 facilitates osteoclast apoptosis and the angiogenesis coupled with osteoclasts. CONCLUSIONS: As pre-osteoblasts undergo maturation, p-Smad3 mediated a paracrine effect that transitions osteoclast cellular behaviors from inducing differentiation and stimulating bone formation to promoting apoptosis and coupling angiogenesis.

Regulation of interstitial fluid flow in adventitia along vasculature by heartbeat and respiration.

Converging studies showed interstitial fluid (ISF) adjacent to blood vessels flows in adventitia along vasculature into heart and lungs. We aim to reveal circulatory pathways and regulatory mechanism of such adventitial ISF flow in rat model. By MRI, real-time fluorescent imaging, micro-CT, and histological analysis, ISF was found to flow in adventitial matrix surrounded by fascia and along systemic vessels into heart, then flow into lungs via pulmonary arteries and back to heart via pulmonary veins, which was neither perivascular tissues nor blood or lymphatic vessels. Under physiological conditions, speckle-like adventitial ISF flow rate was positively correlated with heart rate, increased when holding breath, became pulsative during heavy breathing. During cardiac or respiratory cycle, each dilation or contraction of heart or lungs can generate to-and-fro adventitial ISF flow along femoral veins. Discovered regulatory mechanisms of adventitial ISF flow along vasculature by heart and lungs will revolutionize understanding of cardiovascular system.

Discrimination of opium from Afghanistan and Myanmar by infrared spectroscopy coupled with machine learning methods.

Afghanistan and Myanmar are two overwhelming opium production places. In this study, rapid and efficient methods for distinguishing opium from Afghanistan and Myanmar were developed using infrared spectroscopy (IR) coupled with multiple machine learning (ML) methods for the first time. A total of 146 authentic opium samples were analyzed by mid-IR (MIR) and near-IR (NIR), within them 116 were used for model training and 30 were used for model validation. Six ML methods, including partial least squares discriminant analysis (PLS-DA), orthogonal PLS-DA (OPLS-DA), k-nearest neighbour (KNN), support vector machine (SVM), random forest (RF), and artificial neural networks (ANNs) were constructed and compared to get the best classification effect. For MIR data, the average of precision, recall and f1-score for all classification models were 1.0. For NIR data, the average of precision, recall and f1-score for different classification models ranged from 0.90 to 0.94. The comparison results of six ML models for MIR and NIR data showed that MIR was more suitable for opium geography classification. Compared with traditional chromatography and mass spectrometry profiling methods, the advantages of MIR are simple, rapid, cost-effective, and environmentally friendly. The developed IR chemical profiling methodology may find wide application in classification of opium from Afghanistan and Myanmar, and also to differentiate them from opium originating from other opium producing countries. This study presented new insights into the application of IR and ML to rapid drug profiling analysis.

Comparative oncology chemosensitivity assay for personalized medicine using low-coherence digital holography of dynamic light scattering from cancer biopsies.

Nearly half of cancer patients who receive standard-of-care treatments fail to respond to their first-line chemotherapy, demonstrating the pressing need for improved methods to select personalized cancer therapies. Low-coherence digital holography has the potential to fill this need by performing dynamic contrast OCT on living cancer biopsies treated ex vivo with anti-cancer therapeutics. Fluctuation spectroscopy of dynamic light scattering under conditions of holographic phase stability captures ultra-low Doppler frequency shifts down to 10 mHz caused by light scattering from intracellular motions. In the comparative preclinical/clinical trials presented here, a two-species (human and canine) and two-cancer (esophageal carcinoma and B-cell lymphoma) analysis of spectral phenotypes identifies a set of drug response characteristics that span species and cancer type. Spatial heterogeneity across a centimeter-scale patient biopsy sample is assessed by measuring multiple millimeter-scale sub-samples. Improved predictive performance is achieved for chemoresistance profiling by identifying red-shifted sub-samples that may indicate impaired metabolism and removing them from the prediction analysis. These results show potential for using biodynamic imaging for personalized selection of cancer therapy.

The perioperative experience and needs of hepatocellular carcinoma patients in interventional therapy: a phenomenological qualitative study.

OBJECTIVE: This study aims to investigate the perioperative experience and needs of patients with liver cancer for interventional therapy, in order to provide the basis for further improving a patient's medical experience and satisfaction. METHODS: A semi-structured in-depth interview was conducted for 16 patients with liver cancer in interventional therapy using the phenomenological research method of qualitative research. The themes were analyzed, summarized, refined and extracted using the Colaizzi analytical procedure. RESULTS: The study results revealed that the perioperative experience and needs of patients with liver cancer for interventional therapy could mainly be summarized into seven themes: anxiety, fear and helplessness; not understanding the specific procedures of interventional therapy; worrying that the disease would not be treated as expected; lack of understanding of perioperative adverse reactions and the inability to cope with these; concern on the financial burden of health care costs on families; concerned on the physical and mental health of the dependent; the further improvement of diagnosis and treatment procedures. CONCLUSION: Patients with liver cancer undergo a complex psychological experience during interventional therapy. In clinical practice, a patient's psychological needs and changes should be valued, in order to provide a targeted psychological intervention, health guidance and social support, thereby improving the medical experience and satisfaction of patients.

Anti-GM-CSF autoantibodies predict outcome of cryptococcal meningitis in patients not infected with HIV: A cohort study.

OBJECTIVES: To explore the seroprevalence of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies in non-HIV cryptococcal meningitis (CM) and assess its predictive value for survival. METHODS: This is a retrospective study of 12 years of non-HIV CM. We detected serum anti-GM-CSF autoantibodies, and evaluated the clinical features and outcomes, together with the exploration of prognostic factors for 2-week and 1-year survival. RESULTS: A total of 584 non-HIV CM cases were included. 301 of 584 patients (51.5%) were phenotypically healthy. 264 Cryptococcus isolates were obtained from cerebrospinal fluid (CSF) culture, of which 251 were identified as C. neoformans species complex and 13 as C. gattii species complex. Thirty-seven of 455 patients (8.1%) tested positive for serum anti-GM-CSF autoantibodies. Patients with anti-GM-CSF autoantibodies were more susceptible to C. gattii species complex infection (66.7% vs. 6.3%; p < 0.001) and more likely to develop pulmonary mass lesions with a diameter >3 centimetres (42.9% vs. 6.5%; p 0.001). Of 584 patients 16 (2.7%) died within 2 weeks, 77 of 563 patients (13.7%) died at 1 year, and 93 of 486 patients (19.1%) lived with disabilities at 1 year. Univariant Cox regression analysis found that anti-GM-CSF autoantibodies were associated with lower 1-year survival (HR, 2.66; 95% CI, 1.34-5.27; p 0.005). Multivariable Cox proportional hazards modelling revealed that CSF cryptococcal antigen titres ≥1:1280 were associated with both, reduced 2-week and 1-year survival rates (HR, 5.44; 95% CI, 1.23-24.10; p 0.026 and HR, 5.09; 95% CI, 1.95-13.26; p 0.001). DISCUSSION: Presence of serum anti-GM-CSF autoantibodies is predictive of poor outcomes, regardless of host immune status and the causative Cryptococcus species complex.

Multitask Deep Learning-Based Whole-Process System for Automatic Diagnosis of Breast Lesions and Axillary Lymph Node Metastasis Discrimination from Dynamic Contrast-Enhanced-MRI: A Multicenter Study.

BACKGROUND: Accurate diagnosis of breast lesions and discrimination of axillary lymph node (ALN) metastases largely depend on radiologist experience. PURPOSE: To develop a deep learning-based whole-process system (DLWPS) for segmentation and diagnosis of breast lesions and discrimination of ALN metastasis. STUDY TYPE: Retrospective. POPULATION: 1760 breast patients, who were divided into training and validation sets (1110 patients), internal (476 patients), and external (174 patients) test sets. FIELD STRENGTH/SEQUENCE: 3.0T/dynamic contrast-enhanced (DCE)-MRI sequence. ASSESSMENT: DLWPS was developed using segmentation and classification models. The DLWPS-based segmentation model was developed by the U-Net framework, which combined the attention module and the edge feature extraction module. The average score of the output scores of three networks was used as the result of the DLWPS-based classification model. Moreover, the radiologists' diagnosis without and with the DLWPS-assistance was explored. To reveal the underlying biological basis of DLWPS, genetic analysis was performed based on RNA-sequencing data. STATISTICAL TESTS: Dice similarity coefficient (DI), area under receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and kappa value. RESULTS: The segmentation model reached a DI of 0.828 and 0.813 in the internal and external test sets, respectively. Within the breast lesions diagnosis, the DLWPS achieved AUCs of 0.973 in internal test set and 0.936 in external test set. For ALN metastasis discrimination, the DLWPS achieved AUCs of 0.927 in internal test set and 0.917 in external test set. The agreement of radiologists improved with the DLWPS-assistance from 0.547 to 0.794, and from 0.848 to 0.892 in breast lesions diagnosis and ALN metastasis discrimination, respectively. Additionally, 10 breast cancers with ALN metastasis were associated with pathways of aerobic electron transport chain and cytoplasmic translation. DATA CONCLUSION: The performance of DLWPS indicates that it can promote radiologists in the judgment of breast lesions and ALN metastasis and nonmetastasis. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 3.

Effect of moderate versus deep sedation on recovery following outpatient gastroscopy in older patients: a randomized controlled trial.

BACKGROUND: Although gastrointestinal endoscopy with sedation is increasingly performed in older patients, the optimal level of sedation remains open to debate. In this study, our objective was to compare the effects of moderate sedation (MS) and deep sedation (DS) on recovery following outpatient gastroscopy in elderly patients. METHODS: In this randomized, partially blinded, controlled trial, we randomly divided 270 patients older than 60 years who were scheduled for elective outpatient gastroscopy into the MS or DS group based on the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale. The primary outcome was the duration of stay in the post-anesthesia care unit (PACU). Secondary outcomes included the duration of the total hospital stay, frequency of retching, bucking, and body movements during the examination, endoscopist and patient satisfaction, and sedation-associated adverse events during the procedure. RESULTS: A total of 264 patients completed the study, of whom 131 received MS and 133 received DS. MS was associated with a shorter PACU stay [16.15 ± 9.01 min vs. 20.02 ± 11.13 min, P < 0.01] and total hospital stay [27.32 ± 9.86 min vs. 30.82 ± 12.37 min, P < 0.05], lesser hypoxemia [2.3% (3/131) vs. 12.8% (17/133), P < 0.01], use of fewer vasoactive drugs (P < 0.001), and more retching (P < 0.001). There was no difference in the incidence of bucking and body movements or endoscopist and patient satisfaction between the two groups. CONCLUSION: Compared to deep sedation, moderate sedation may be a preferable choice for American Society of Anesthesiologists (ASA) Grade I-III elderly patients undergoing outpatient gastroscopies, as demonstrated by shorter PACU stays and total hospital stays, lower sedation-associated adverse events, and similar levels of endoscopist and patient satisfaction.

PD-L1 blockade TAM-dependently potentiates mild photothermal therapy against triple-negative breast cancer.

The present work was an endeavor to shed light on how mild photothermia possibly synergizes with immune checkpoint inhibition for tumor therapy. We established mild photothermal heating protocols to generate temperatures of 43 °C and 45 °C in both in vitro and in vivo mouse 4T1 triple-negative breast cancer (TNBC) models using polyglycerol-coated carbon nanohorns (CNH-PG) and 808 nm laser irradiation. Next, we found that 1) CNH-PG-mediated mild photothermia (CNH-PG-mPT) significantly increased expression of the immune checkpoint PD-L1 and type-1 macrophage (M1) markers in the TNBC tumors; 2) CNH-PG-mPT had a lower level of anti-tumor efficacy which was markedly potentiated by BMS-1, a PD-L1 blocker. These observations prompted us to explore the synergetic mechanisms of CNH-PG-mPT and BMS-1 in the context of tumor cell-macrophage interactions mediated by PD-L1 since tumor-associated macrophages (TAMs) are a major source of PD-L1 expression in tumors. In vitro, the study then identified two dimensions where BMS-1 potentiated CNH-PG-mPT. First, CNH-PG-mPT induced PD-L1 upregulation in the tumor cells and showed a low level of cytotoxicity which was potentiated by BMS-1. Second, CNH-PG-mPT skewed TAMs towards an M1-like anti-tumor phenotype with upregulated PD-L1, and BMS-1 bolstered the M1-like phenotype. The synergistic effects of BMS-1 and CNH-PG-mPT both on the tumor cells and TAMs were more pronounced when the two cell populations were in co-culture. Further in vivo study confirmed PD-L1 upregulation both in tumor cells and TAMs in the TNBC tumors following treatment of CNH-PG-mPT. Significantly, TAMs depletion largely abolished the anti-TNBC efficacy of CNH-PG-mPT alone and in synergy with BMS-1. Collectively, our findings reveal PD-L1 upregulation to be a key response of TNBC to mild photothermal stress, which plays a pro-survival role in the tumor cells while also acting as a brake on the M1-like activation of the TAMs. Blockade of mPT­induced PD­L1 achieves synergistic anti-TNBC efficacy by taking the intrinsic survival edge off the tumor cells on one hand and taking the brakes off the M1-like TAMs on the other. Our findings reveal a novel way (i.e. mild thermia plus PD-L1 blockade) to modulate the TAMs-tumor cell interaction to instigate a mutiny of the TAMs against their host tumor cells.

Geographical classification of opium samples from Myanmar and Afghanistan by NMR profiling and chemometrics.

This study presents a new strategy to discriminate between opium samples obtained from different geographical regions. Nuclear magnetic resonance (NMR) profiling and chemometrics were applied to geographical classification of opium originating from Myanmar and Afghanistan, which are two major opium producing countries in the world. A total of 50 Myanmar and 46 Afghanistan authentic opium samples were analyzed by 1 H-NMR, and the chemical profiles were characterized. Different sample preparation procedures, data processing methods, and chemometrics were compared to obtain the best classification effect. It was found that drying and the addition of buffer solutions were unnecessary for classification purposes; thus, the gum opium samples were extracted directly with CD3 OD, which shortened sample preparation time. A full discrimination between the two geographical origins was achieved by 1 H-NMR profiling and orthogonal partial least squares discriminant analysis. All 30 opium samples were classified correctly by the developed orthogonal partial least squares discriminant analysis model. Compared with traditional chromatography and mass spectrometry profiling methods, the 1 H-NMR profiling method was faster (with instrument analysis time of less than 3 min) and reproducible. This study provides new insights into the applying of NMR profiling and chemometrics to rapid drug profiling analysis.

Qualitative and Quantitative Analysis of Five Indoles or Indazole Amide Synthetic Cannabinoids in Suspected E-Cigarette Oil by GC-MS.

OBJECTIVES: To establish the GC-MS qualitative and quantitative analysis methods for the synthetic cannabinoids, its main matrix and additives in suspicious electronic cigarette (e-cigarette) oil samples. METHODS: The e-cigarette oil samples were analyzed by GC-MS after diluted with methanol. Synthetic cannabinoids, its main matrix and additives in e-cigarette oil samples were qualitatively analyzed by the characteristic fragment ions and retention time. The synthetic cannabinoids were quantitatively analyzed by using the selective ion monitoring mode. RESULTS: The linear range of each compound in GC-MS quantitative method was 0.025-1 mg/mL, the matrix recovery rate was 94%-103%, the intra-day precision relative standard deviations (RSD) was less than 2.5%, and inter-day precision RSD was less than 4.0%. Five indoles or indazole amide synthetic cannabinoids were detected in 25 e-cigarette samples. The main matrixes of e-cigarette samples were propylene glycol and glycerol. Additives such as N,2,3-trimethyl-2-isopropyl butanamide (WS-23), glycerol triacetate and nicotine were detected in some samples. The content range of synthetic cannabinoids in 25 e-cigarette samples was 0.05%-2.74%. CONCLUSIONS: The GC-MS method for synthesizing cannabinoid, matrix and additive in e-cigarette oil samples has good selectivity, high resolution, low detection limit, and can be used for simultaneous qualitative and quantitative analysis of multiple components; The explored fragment ion fragmentation mechanism of the electron bombardment ion source of indole or indoxamide compounds helps to identify such substances or other compounds with similar structures in cases.

Genetic Diversity of Domestic Cat Hepadnavirus in Southern Taiwan.

Domestic cat hepadnavirus (DCH) is an infectious disease associated with chronic hepatitis in cats, which suggests a similarity with hepatitis B virus infections in humans. Since its first identification in Australia in 2018, DCH has been reported in several countries with varying prevalence rates, but its presence in Taiwan has yet to be investigated. In this study, we aimed to identify the presence and genetic diversity of DCH infections in Taiwan. Among the 71 samples tested, eight (11.27%) were positive for DCH. Of these positive cases, three cats had elevated levels of alanine transaminase (ALT) and aspartate transaminase (AST), suggesting an association between DCH infection and chronic hepatitis. Four DCH-positive samples were also tested for feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) coinfection. One sample (25%) was positive for FIV, whereas there was no positive sample for FeLV (0%). In addition, we performed whole genome sequencing on six samples to determine the viral genome sequences. Phylogenetic analyses identified a distinct lineage compared with previously reported sequences. This study highlights the importance of continuous surveillance of DCH and further research to elucidate the pathophysiology and transmission route of DCH.

Effect of regional anesthesia and analgesia on long-term survival following abdominal cancer Surgery-A systematic review with meta-analysis.

Background: The impact of regional anesthesia and analgesia (RAA) on long-term survival following cancer surgery is a topic of debate. The aim of this study was to investigate the effects of perioperative RAA on long-term oncological outcomes in patients undergoing major abdominal cancer surgery. Methods: The authors searched computerized databases and reference lists from inception to December 20, 2022. All studies that investigated the effects of perioperative RAA on long-term oncological outcomes following major abdominal cancer surgery were included. Using the inverse variance method with a random-effects model, hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Results: The systematic review included 51 retrospective studies, one prospective study, and three randomized controlled trials (RCTs), with a total of 95,046 patients. The results showed that perioperative RAA may improve long-term overall survival (HR: 0.85, 95% CI: 0.80 to 0.91, P = 0.00, I2 = 60.2%). However, there was no significant association between perioperative RAA and reduced cancer recurrence (HR: 0.98, 95% CI: 0.90 to 1.03, P = 0.31, I2 = 52.3%). When performing a pooled analysis of the data from the three RCTs, no statistically significant effect of RAA was found in either case. Conclusion: The systematic review suggests perioperative RAA may improve long-term overall survival but does not appear to reduce cancer recurrence in patients undergoing major abdominal cancer surgery. The limited number of RCTs included in this study did not confirm this finding, highlighting the need for further RCTs to corroborate these results.

Distinctive magnetic resonance imaging features in primary central nervous system lymphoma: A case report.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare malignant tumor originating from the lymphatic hematopoietic system. It exhibits unique imaging manifestations due to its biological characteristics. CASE SUMMARY: Magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), and magnetic resonance spectroscopy was performed. The imaging findings showed multiple space-occupying lesions with low signal on T1-weighted imaging, uniform high signal on T2-weighted imaging, and obvious enhancement on contrast-enhanced scans. DWI revealed diffusion restriction, PWI demonstrated hypoperfusion, and spectroscopy showed elevated choline peak and decreased N-acetylaspartic acid. The patient's condition significantly improved after hormone shock therapy. CONCLUSION: This case highlights the distinctive imaging features of PCNSL and their importance in accurate diagnosis and management.