Optomechanically-induced nonreciprocal conversion between microwave and optical photons.

We theoretically propose a scheme of the nonreciprocal conversion device between photons of two arbitrary frequencies in a hybrid cavity optomechanical system, where two optical cavities and two microwave cavities are coupled to two different mechanical resonators via radiation pressure. Two mechanical resonators are coupled together via the Coulomb interaction. We study the nonreciprocal conversions between both the same and different types of frequency photons. The device is based on multichannel quantum interference to break the time-reversal symmetry. Our results show the perfect nonreciprocity conditions. By adjusting the Coulomb interaction and the phase differences, we find that the nonreciprocity can be modulated and even transformed into reciprocity. These results provide new insight into the design of nonreciprocal devices, including isolators, circulators, and routers in quantum information processing and quantum networks.

Inhibition of Phosphoinositide 3-Kinase Gamma Protects Endothelial Cells via the Akt Signaling Pathway in Sepsis-Induced Acute Kidney Injury.

INTRODUCTION: Sepsis is a primary cause of death in critically ill patients and is characterized by multiple organ dysfunction, including sepsis-induced acute kidney injury (AKI), which contributes to high mortality in sepsis. However, its pathophysiological mechanisms remain unclear. The kidney has one of the richest and most diversified endothelial cell populations in the body. This study was designed to investigate the effects of endothelial dysfunction in sepsis-induced AKI and explore possible intervention measures to offer new insight into the pathogenesis and treatment of sepsis-induced AKI. METHODS: The circulating levels of endothelial adhesion molecules were detected in patients with sepsis and healthy controls to observe the role of endothelial damage in sepsis and sepsis-induced AKI. A murine sepsis model induced by cecal ligation and perforation was pretreated with a phosphoinositide 3-kinase gamma (PI3Kγ) inhibitor (CZC24832), and survival, kidney damage, and renal endothelial injury were assessed by pathological examination, immunohistochemistry, quantitative polymerase chain reaction, and Western blotting. Lipopolysaccharides and CZC24832 were administered to human umbilical vein endothelial cells in vitro, and endothelial cell function and the expression of adhesion molecules were evaluated. RESULTS: Endothelial damage was more serious in sepsis-induced AKI than that in non-AKI, and the inhibition of PI3Kγ alleviates renal endothelial injury in a murine sepsis model, protecting endothelial cell function and repairing endothelial cell injury through the Akt signaling pathway. CONCLUSIONS: In this study, endothelial cell dysfunction plays an important role in sepsis-induced AKI, and the inhibition of PI3Kγ alleviates endothelial cell injury in sepsis-induced AKI through the PI3Kγ/Akt pathway, providing novel targets for treating sepsis and related kidney injury.

Immunotherapy combined with antiangiogenic therapy as third- or further-line therapy for stage IV non-small cell lung cancer patients with ECOG performance status 2: A retrospective study.

BACKGROUND: Patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 2 probably cannot tolerate chemotherapy or other antitumor therapies. Some studies have reported that immunotherapy combined with antiangiogenic therapy is well-tolerated and shows good antitumor activity. However, the efficacy of this combination as a later-line therapy in patients with ECOG PS 2 is unclear. This study evaluated the effectiveness and safety of this combination strategy as third- or further-line therapy in stage IV non-small cell lung cancer (NSCLC) patients with ECOG PS 2. METHODS: In this retrospective study, patients treated with camrelizumab plus antiangiogenic therapy (bevacizumab, anlotinib, or recombinant human endostatin) were included. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), quality of life (QOL) assessed by ECOG PS, and safety were analyzed. RESULTS: Between January 10, 2019, and February 28, 2024, a total of 59 patients were included. The ORR was 35.6% (21/59) and the DCR was 86.4%. With a median follow-up of 10.5 months (range: 0.7-23.7), the median PFS was 5.5 months (95% confidence interval [CI]: 3.8-7.3) and the median OS was 10.5 months (95% CI: 11.2-13.6). QOL was improved (≥1 reduction in ECOG PS) in 39 patients (66.1%). The most common Grade 3-4 treatment-related adverse events were hepatic dysfunction (6 [10%]), hypertension (5 [8%]), and hypothyroidism (3 [5%]). There were no treatment-related deaths. CONCLUSIONS: Third- or further-line immunotherapy combined with antiangiogenic therapy is well-tolerated and shows good antitumor activity in stage IV NSCLC patients with ECOG PS 2. Future large-scale prospective studies are required to confirm the clinical benefits of this combination therapy.

Correlation between serum laminin levels and prognosis of acute myocardial infarction.

Background: Acute myocardial infarction (AMI) is a critical cardiovascular disease (CVD). Laminin (LN) is involved in the process of myocardial fibrosis and ventricular remodeling observed in AMI; however, there are currently no studies on the correlation between LN and AMI prognosis. Purpose: To explore the predictive value of serum LN levels for major adverse cardiovascular events (MACE) in patients, 6 months after an acute myocardial infarction. Methods: A total of 202 AMI patients who were hospitalized in the Department of Cardiology of the Second Affiliated Hospital of Nantong University between December 2019 and December 2020 were included. The observation endpoint was the occurrence of MACE. Univariate and multivariate logistic analyses were used to evaluate the relationships between the variables and endpoint. The predictive value of LN for MACE in AMI patients was assessed using receiver operating characteristic (ROC) analysis. Results: A total of 47 patients developed MACE. Univariate logistic analysis showed that smoking, emergency percutaneous coronary intervention (EPCI), age, cardiac troponin I (c-TNI) levels, N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels, and LN levels were associated with the occurrence of MACE (p < 0.05). Multivariate logistic analysis showed that LN was an independent predictor of MACE (odds ratio [OR] = 1.021, 95%CI: 1.014-1.032, p < 0.001). According to the ROC curve, LN can be used as an effective predictor of MACE (AUC = 0.856, 95%CI: 0.794-0.918, p < 0.001). According to the cutoff value, LN>58.80 ng/ml (sensitivity = 83.00%, specificity = 76.80%) or LN>74.15 ng/ml (sensitivity = 76.6%, specificity = 83.2%) indicate a poor prognosis for AMI. Different cut-off values are selected according to the need for higher sensitivity or specificity in clinical applications. Conclusions: LN may be a predictor of MACE following AMI in patients and could be utilized as a novel substitute marker for the prevention and treatment of AMI.

MAIT cells predict long-term prognosis in liver failure patients.

BACKGROUND: Liver failure (LF) is a life-threatening clinical syndrome characterized by intense systemic inflammation and organ failure(s), leading to a high mortality rate. The pathogenesis of LF is multifactorial, immune response, and gut bacterial translocation are thought to be major contributing factors. Mucosal-associated invariant T (MAIT) cells play a critical role in immune response and gut bacterial translocation. We aimed to investigate changes of the MAIT cell ratio in patients with LF and to explore the predictive value for long-term prognosis in patients with LF. MATERIAL AND METHOD: We recruited 75 patients with LF from Nantong Third People's Hospital, isolated peripheral blood mononuclear cells, and detected the proportion of circulating MAIT cells by flow cytometry. Statistical analyses were performed using the GraphPad Prism software. RESULTS: Our data showed that the proportion of MAIT cells alterations was independent of the cause of viral infection in patients with LF. Kaplan-Meier survival analysis showed that LF patients with low level of MAIT cells had poor long-term prognosis. The area under the receiver operating characteristic curve of the MAIT cell proportion was larger than that of the Model for End-Stage Liver Disease (MELD) score. More importantly, the combination of MAIT cell proportion and MELD score had a better effect in predicting long-term prognosis of LF patients than any single index (AUC = 0.91, 95% CI:0.84-0.97), and multivariate logistic regression analysis indicated that the circulating MAIT cell proportion was an independent risk factor for LF. CONCLUSION: The proportion of MAIT cells in PBMC is an outstanding predictor for the long-term prognosis in patients with LF.

2b or Not 2b: How Opposing FGF Receptor Splice Variants Are Blocking Progress in Precision Oncology.

More than ten thousand peer-reviewed studies have assessed the role of fibroblast growth factors (FGFs) and their receptors (FGFRs) in cancer, but few patients have yet benefited from drugs targeting this molecular family. Strategizing how best to use FGFR-targeted drugs is complicated by multiple variables, including RNA splicing events that alter the affinity of ligands for FGFRs and hence change the outcomes of stromal-epithelial interactions. The effects of splicing are most relevant to FGFR2; expression of the FGFR2b splice isoform can restore apoptotic sensitivity to cancer cells, whereas switching to FGFR2c may drive tumor progression by triggering epithelial-mesenchymal transition. The differentiating and regulatory actions of wild-type FGFR2b contrast with the proliferative actions of FGFR1 and FGFR3, and may be converted to mitogenicity either by splice switching or by silencing of tumor suppressor genes such as CDH1 or PTEN. Exclusive use of small-molecule pan-FGFR inhibitors may thus cause nonselective blockade of FGFR2 isoforms with opposing actions, undermining the rationale of FGFR2 drug targeting. This splice-dependent ability of FGFR2 to switch between tumor-suppressing and -driving functions highlights an unmet oncologic need for isoform-specific drug targeting, e.g., by antibody inhibition of ligand-FGFR2c binding, as well as for more nuanced molecular pathology prediction of FGFR2 actions in different stromal-tumor contexts.

Efficacy and Safety Aiming at the Combined-Modality Therapy of External Beam Radiotherapy (40Gy) and Iodine-125 Seed Implantation for Locally Advanced NSCLC in the Elderly.

PURPOSE: To evaluate the efficacy and safety of combined-modality therapy for elderly patients with locally advanced non-small-cell lung cancer (NSCLC) invading the chest wall. PATIENTS AND METHODS: We retrospectively enrolled 21 elderly patients (aged ≥60 years) with locally advanced NSCLC invading the chest wall. For external beam radiotherapy (EBRT) of the primary tumor, 40Gy was applied and supplemented with iodine-125 seed implantation while 60Gy was applied to the lymph nodes of the mediastinum. Follow-up was conducted every 3 months postoperatively. The related analytic parameters were change in tumor size, the objective response rate (ORR), the disease control rate (DCR), the degree of pain relief, the improvement of physical status, and toxicity. RESULTS: The combined-modality therapy significantly inhibited local growth of the tumor (from 7.84±1.20 to 4.69±1.90 cm) (P <0.0001), with 71.4% ORR and 90.5% DCR at 1 year. The cancer-related pain was significantly relieved (P <0.05) and physical status was significantly improved (P <0.05). No procedure-associated death or grade > 2 irradiation-related adverse effects were reported in this study. CONCLUSION: The combined-modality therapy of EBRT with 40Gy and permanent iodine-125 seed implantation is an efficacious and safe treatment option for elderly patients with locally advanced NSCLC invading the chest wall.

[Analysis of milk and dairy products by near-infrared spectroscopy: a review].

As a highly efficient, convenient and nondestructive detection method, near-infrared spectroscopy (NIRS) is appropriate for the analysis of milk and dairy products. The present review discusses the principle of the near-infrared spectroscopy analysis technology and the evaluation standard criteria of milk and dairy products, and also reviews the hardware device technology and the data processing technique for the analysis of milk and dairy products in order to promote the application of near-infrared spectroscopy analysis technology in milk and dairy products quality control in China.

An effective perineal procedure for the management of full-thickness rectal prolapse.

AIMS: To evaluate the clinical and functional outcome of transanal purse-string sutures for rectal mucosa and submucosa plus perianal suture (TAS-PAS) for the management of full-thickness rectal prolapse. METHODS: The clinical data of 62 patients with full-thickness rectal prolapse treated with TAS-PAS between March 2000 and March 2008 were analyzed retrospectively. RESULTS: No patient died. Satisfaction with surgery was high in 50 cases (80.6%), moderate in 9 cases (14.5%), and low in 3 cases (4.84%). Prolapse relapse rate was 4.84%. Anal continence improved in 82.6% of patients, constipation improved in 69.2%, and anal tenesmus in 86.7%. No surgery-associated constipation occurred. The mean operative time was 52 min (range 40-80). Mean hospital stay was 4 days (range 3-7). Mean patient follow-up was 17 months (range 4-36). CONCLUSIONS: From our data, TAS-PAS for the management of full-thickness rectal prolapse showed encouraging results with little complications and an acceptable relapse rate. This procedure induces only mild trauma and is easy to perform making it worthy of further practice and investigation.

Pressure distributions inside intervertebral discs under unilateral pedicle screw fixation in a porcine spine model.

BACKGROUND: Little data are available regarding the effects of pedicle screws on the intervertebral disc stress for different spinal segments. The aim of this study was to analyze the intervertebral disc stress in response to the placement of pedicle screws. METHODS: T3-4, T11-12, T15-L1, L3-4, and L4-5 intervertebral disc segments from six porcine spine specimens were harvested. A compressive load of 200 N was applied both before and after the pedicle screw was implanted on the left side of each target segment; the resulting pressure was measured during vertical, 5° anterior flexion, 5° posterior extension, and 5° lateral bending. RESULTS: The posterior intradiscal pressures of the intervertebral disc were significantly lower in the fixed group than in the unfixed group for all segments during vertical, 5° anterior flexion, and 5° posterior extension. The left pressures of the intervertebral disc were significantly lower in the fixation group for all segments. During 5° lateral bending, the left intervertebral disc pressures were significantly lower in the fixation group. Lower mean pressures were observed in the fixed group. CONCLUSIONS: Unilateral pedicle screws can effectively reduce the pressure of the fixed lateral intervertebral disc. Moreover, it can change the pressure distribution of the intervertebral disc and reduce the pressure of the entire intervertebral disc, especially the posterior side of the intervertebral disc.

Ablative Hypofractionated Radiation Therapy Enhances Non-Small Cell Lung Cancer Cell Killing via Preferential Stimulation of Necroptosis In Vitro and In Vivo.

PURPOSE: To investigate how necroptosis (ie, programmed necrosis) is involved in killing of non-small cell lung cancer (NSCLC) after ablative hypofractionated radiation therapy (HFRT). METHODS AND MATERIALS: Deoxyribonucleic acid damage, DNA repair, and the death form of NSCLC cells were assessed after radiation therapy. The overexpression and silencing of receptor-interacting protein kinases 3 (RIP3, a key protein involved activation of necroptosis)-stable NSCLC cell lines were successfully constructed. The form of cell death, the number and area of colonies, and the regulatory proteins of necroptosis were characterized after radiation therapy in vitro. Finally, NSCLC xenografts and patient specimens were used to examine involvement of necroptosis after ablative HFRT in vivo. RESULTS: Radiation therapy induced expected DNA damage and repair of NSCLC cell lines, but ablative HFRT at ≥10 Gy per fraction preferentially stimulated necroptosis in NSCLC cells and xenografts with high RIP3 expression, as characterized by induction and activation of RIP3 and mixed-lineage kinase domain-like protein and release of immune-activating chemokine high-mobility group box 1. In contrast, RNA interference of RIP3 attenuated ablative HFRT-induced necroptosis and activation of its regulatory proteins. Among central early-stage NSCLC patients receiving stereotactic body radiation therapy, high expression of RIP3 was associated with improved local control and progression-free survival (all P < .05). CONCLUSIONS: Ablative HFRT at ≥10 Gy per fraction enhances killing of NSCLC with high RIP3 expression via preferential stimulation of necroptosis. RIP3 may serve as a useful biomarker to predict favorable response to stereotactic body radiation therapy.

Isosteroidal alkaloids as potent dual-binding site inhibitors of both acetylcholinesterase and butyrylcholinesterase from the bulbs of Fritillaria walujewii.

Five new isosteroidal alkaloids, walujewine A (1), walujewine B (4), walujewine C (5), walujewine D (6), walujewine E (10) were isolated from the bulbs of Fritillaria walujewii together with seven known isosteroidal alkaloids (2, 3, 7-9, 11, 12). Their structures were elucidated on the basis of IR, ESI-MS, HR-ESI-MS, 1D and 2D NMR spectroscopic data analyses and single-crystal X-ray diffraction. All the isolates were tested for ChE inhibiting activity by the Ellman's method. Compounds 3-5 and 8-10 were potent dual AChE-BChE inhibitors, and compound 1 showed highly selective AChE inhibition. The structure-activity relationship of compounds 1-12 was discussed in details. And kinetic analysis showed that compounds 1, 3-5, and 8-10 were mixed-type reversible inhibitors of AChE, simultaneously binding to the catalytic and peripheral anionic sites, which was verified by in silico docking studies. The docking simulation also showed that active compound 3 and 8 created many interactions with the CAS and PAS gorges of BChE, revealing their mixed-type inhibition. ADMET analysis further confirmed the therapeutic potential of some isosteroidal alkaloids based on their high BBB-penetration.

[Clinical characteristics and potential prognostic factors of breast cancer patients with liver metastases].

OBJECTIVE: To analyze the clinical characteristics, efficiency of treatment and potential prognostic factors of breast cancer patients with liver metastases (BCLM). METHODS: The data of clinical characteristics, response to treatment and survival were retrospectively analyzed in 152 breast cancer patients with liver metastasis using SPSS 11.5. RESULTS: The median disease free survival (DFS), the median survival of recurrence (MSR) and median time to progress (TTP) of this series was 21 months, 16 months and 7.4 months, respectively. The response rate in chemotherapy group was higher than that in the transcatheter arterial chemoembolization (TACE) group (37.7% vs. 53%, P = 0. 039). The TTP was longer (7 m vs. 10 m, P = 0.048) and the response rate (63.3% vs. 40.0%, P = 0.04) in taxanes-based chemotherapy group was significantly higher than that in non-taxanes-containing regimen. The MSR in patients with single liver metastases treated by TACE was longer than that by chemotherapy (16 m vs. 30 m, P = 0.0052), but it was not observed in the patients with multiple metastases. Pathological tumor size (PT) and axillary lymph node status at diagnosis, negative estrogen receptor (ER) status, abnormal ALT level induced by liver metastases, metastastic tumor size were significantly correlated with shorter survival. CONCLUSION: The effective chemotherapy especially the taxane-containing regimen and TACE may improve outcome for breast cancer patient with liver metastasis.

A comparison between cyberknife and neurosurgery in solitary brain metastases from non-small cell lung cancer.

PURPOSE: To evaluate the efficacy of cyberknife (CK) and neurosurgery (NS) in patients newly diagnosed as solitary brain metastasis (SBM) from non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: We retrospectively analyzed 76 patients between 1990 and 2012 from our institution, including 38 patients performing CK and the other half performing NS. The observation end point was overall survival time (OS), local control of treated metastasis (LC) and intracranial control (IC). Kaplan-Meier OS curves were compared with the log-rank test. Cox regression analysis was used to determine prognosticators for OS, LC and IC. RESULTS: The baseline characteristic between the two groups was not significantly different. The 1-year OS rates were 53.5% and 30.5% in the CK group and NS group, respectively, (p=0.121). The 1-year LC rates were 50.8% and 31.3%, respectively, (p=0.078). The 1-year IC rates were 50.8% and 27.7%, respectively, (p=0.066). In multivariate analysis, improved OS was significantly associated with younger age (p=0.016), better ECOG performance status (p=0.000) and graded prognostic assessment (GPA, 3.5-4.0, p=0.006). The LC was also associated with better ECOG performance status (p=0.000). The IC was associated with both better ECOG performance status (p=0.000) and GPA (3.5-4.0, p=0.005). CONCLUSIONS: There was no statistical difference between CK and NS for SBM from NSCLC in OS, LC and IC. However, CK is less invasive and may be more acceptable for patients. The result needs randomized trials to confirm and further study.

Radiotherapy and chemotherapy are associated with improved outcomes over surgery and chemotherapy in the management of limited-stage small cell esophageal carcinoma.

BACKGROUND: This retrospective study evaluates the efficacy and safety of surgery and chemotherapy (S +CT) vs. radiotherapy and CT (RT+CT) in patients with limited stage small cell esophageal cancer (LS-SCEC). PATIENTS AND METHODS: Patients included in analysis (from our hospital and the literature) were treated with S+CT or RT+CT between 1989 and 2012. The primary end point was overall survival (OS); secondary end points included tumor response and toxicity. Kaplan-Meier OS curves were compared with the log-rank test. Cox regression analysis was used to determine prognosticators for OS. RESULTS: A total of 127 patients were included: 14 from our hospital and 113 from the literature. Fifty-four (43%) and 73 (57%) patients received S+CT or RT+CT, respectively. The median OS of all patients was 21.0 months. OS was longer for those who received RT+CT rather than S+CT (33.0 vs. 17.5 months, p=0.02), especially those with N1 disease. Uni- and multi-variate analyses showed tumor location (upper 1/3rd of esophagus) and type of treatment (S+CT) were poor prognostic factors of OS. CONCLUSION: LS-SCEC patients treated with RT+CT had an improved OS compared to those treated with S+RT. Thus, RT+CT should be considered as a primary approach for these patients.

Late course accelerated hyperfractionation radiotherapy for locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Late course accelerated hyperfractionation radiotherapy (LCAHR) is used as a standard treatment option for locally advanced esophageal squamous cell carcinoma (LAESCC) in China, but concerns remain regarding its efficacy and safety. The purpose of this paper was to evaluate the efficacy and safety of LCAHR. The comparisons examined were as follows: LCAHR versus conventional fractionation radiotherapy (CFR) and LCAHR plus chemotherapy (CT) versus LCAHR alone. METHODS: We searched the Cochrane Library, MEDLINE, EMBASE, CENTRAL, CBMdisc, and CNKI, as well as employing manual searches. The primary end points were survival and local control. The second end point was toxicities. RESULTS: Based on search criteria, we found 29 trials involving 3187 patients. Our results showed that LCAHR, compared with CFR, improved the survival and local control, and was, thus, more therapeutically beneficial. Further analysis revealed that LCAHR plus CT proved to be better for patients' survival and local control compared to LCAHR alone. Acute toxicities were increased rather than late toxicities. CONCLUSIONS: There was a significant survival and local control benefit of LCAHR over CFR, as well as LCAHR plus CT over LCAHR alone. Considering the strength of the evidence, the results of this study indicate that this regimen would be a new promising modality worth further investigation.

[Quantitative driving analysis of forest biomass changes in Changbai Mountain forest region].

Based on the forest inventory data and single tree biomass model, the forest biomass in the sampling plots in Changbai Mountain forest region was calculated, and, by using the estimated forest biomass from four periods' remote sensing data and based on high accuracy remote sensing models, the changes of regional forest biomass were analyzed. In the meanwhile, the driving factors such as meteorological factors, management factors, and socio-economic factors that caused forest biomass change were selected by bootstrap method, and the driving model of forest biomass change in different time period was set up by using partial least-squares method. The Variable Importance in Projection (VIP) values representing the importance of each of the factors affecting the forest biomass change in study region were calculated. The results showed that the influence of human activity factors (VIP values) on Changhai Mountain forest biomass changes was less than that of natural factors, suggesting that the national forest protection policy for forest regions had played an obvious role. Our research broadened the content of forest biomass change driving analysis, and the introduction of calculating VIP value, which can quantitatively represent the influence of driving factors to forest biomass change, provided a new way for the quantitative analysis on forest biomass change.