The Mitochondrial-Derived Peptide MOTS-c Alleviates Radiation Pneumonitis via an Nrf2-Dependent Mechanism.

Radiation pneumonitis (RP) is a prevalent and fatal complication of thoracic radiotherapy due to the lack of effective treatment options. RP primarily arises from mitochondrial injury in lung epithelial cells. The mitochondrial-derived peptide MOTS-c has demonstrated protective effects against various diseases by mitigating mitochondrial injury. C57BL/6 mice were exposed to 20 Gy of lung irradiation (IR) and received daily intraperitoneal injections of MOTS-c for 2 weeks. MOTS-c significantly ameliorated lung tissue damage, inflammation, and oxidative stress caused by radiation. Meanwhile, MOTS-c reversed the apoptosis and mitochondrial damage of alveolar epithelial cells in RP mice. Furthermore, MOTS-c significantly inhibited oxidative stress and mitochondrial damage in MLE-12 cells and primary mouse lung epithelial cells. Mechanistically, MOTS-c increased the nuclear factor erythroid 2-related factor (Nrf2) level and promoted its nuclear translocation. Notably, Nrf2 deficiency abolished the protective function of MOTS-c in mice with RP. In conclusion, MOTS-c alleviates RP by protecting mitochondrial function through an Nrf2-dependent mechanism, indicating that MOTS-c may be a novel potential protective agent against RP.

Based on polydopamine-coated metal organic framework multifunctional nanoplatform for enhanced photothermal/sonodynamicand treatment combined with checkpoint blockade therapy.

To overcome the low efficacy of sonodynamic therapy (SDT) caused by hypoxia in the tumor microenvironment, we developed a multiple anti-tumor nanoplatform with synergistic SDT, photothermal therapy (PTT), and ferroptosis effects. PCN-224@FcCaO2/Mn/dihydroartemisinin/imiquimod/PDA (PFC) was prepared by modified with dihydroartemisinin (DHA), imiquimod (R837), CaO2, ferrocene (Fc) and Mn2+ on the PCN-224 (Cu) to achieve self-replenishment of H2O2/O2 and GSH consumption. FcCaO2 decomposed into H2O2 in the tumor microenvironment, triggering the Fenton effect to produce OH, and Cu2+ reduced the potential loss of OH by the depletion of GSH. Under ultrasonic (US) and laser irradiation, PFC exhibits exciting PTT and SDT effects from polydopamine (PDA) and PCN-224. Mn2+ not only promoted the reaction of H2O2 to produce O2 to effectively enhance SDT but also induced tumor cell apoptosis by Mn2+ combined with DHA. PFC induced ferroptosis via Fe interaction with DHA to produce ROS and reduce the expression of GPX4. The released R837 and tumor-associated antigens from SDT/PTT can produce damage associated molecular patterns (DAMPs), which can initiate adaptive immune responses to kill cancer cells, and released again to promote the tumor immune cycle. What's more, SDT/PTT and ferroptosis combined with aPD-L1 can effectively suppress both primary and distant tumor growth.

Intrarenal pressure detection during flexible ureteroscopy with fiber optic pressure sensor system in porcine model.

To validate the feasibility of a fiber-optic pressure sensor-based pressure measurement device for monitoring intrarenal pressure and to analyze the effects of ureteral acess sheath (UAS) type, surgical location, perfusion flow rate, and measurement location on intrarenal pressure (IRP). The measurement deviations and response times to transient pressure changes were compared between a fiber-optic pressure sensing device and a urodynamic device IRP in an in vitro porcine kidney and in a water tank. Finally, pressure measurements were performed in anesthetized female pigs using fiber-optic pressure sensing device with different UAS, different perfusion flow rates, and different surgical positions at different renal calyces and ureteropelvic junctions (UPJ). According to our operation, the result is fiber optic pressure sensing devices are highly accurate and sensitive. Under the same conditions, IRP varied among different renal calyces and UPJ (P < 0.05). IRP was lowest at 50 ml/min and highest at 150 ml/min (P < 0.05). Surgical position had a significant effect on IRP (P < 0.05). 12/14 Fr UAS had a lower IRP than 11/13 Fr UAS. Therefore fiber optic pressure sensing devices are more advantageous for IRP measurements. In ureteroscopy, the type of ureteral sheath, the surgical position, the perfusion flow rate, and the location of the measurement all affect the intrarenal pressure value.

Enhancing the prediction of symptomatic radiation pneumonitis for locally advanced non-small-cell lung cancer by combining 3D deep learning-derived imaging features with dose-volume metrics: a two-center study.

OBJECTIVE: This study aims to examine the ability of deep learning (DL)-derived imaging features for the prediction of radiation pneumonitis (RP) in locally advanced non-small-cell lung cancer (LA-NSCLC) patients. MATERIALS AND METHODS: The study cohort consisted of 90 patients from the Fudan University Shanghai Cancer Center and 59 patients from the Affiliated Hospital of Jiangnan University. Occurrences of RP were used as the endpoint event. A total of 512 3D DL-derived features were extracted from two regions of interest (lung-PTV and PTV-GTV) delineated on the pre-radiotherapy planning CT. Feature selection was done using LASSO regression, and the classification models were built using the multilayered perceptron method. Performances of the developed models were evaluated by receiver operating characteristic curve analysis. In addition, the developed models were supplemented with clinical variables and dose-volume metrics of relevance to search for increased predictive value. RESULTS: The predictive model using DL features derived from lung-PTV outperformed the one based on features extracted from PTV-GTV, with AUCs of 0.921 and 0.892, respectively, in the internal test dataset. Furthermore, incorporating the dose-volume metric V30Gy into the predictive model using features from lung-PTV resulted in an improvement of AUCs from 0.835 to 0.881 for the training data and from 0.690 to 0.746 for the validation data, respectively (DeLong p < 0.05). CONCLUSION: Imaging features extracted from pre-radiotherapy planning CT using 3D DL networks could predict radiation pneumonitis and may be of clinical value for risk stratification and toxicity management in LA-NSCLC patients. CLINICAL RELEVANCE STATEMENT: Integrating DL-derived features with dose-volume metrics provides a promising noninvasive method to predict radiation pneumonitis in LA-NSCLC lung cancer radiotherapy, thus improving individualized treatment and patient outcomes.

Effect of bolus materials on dose deposition in deep tissues during electron beam radiotherapy.

Several materials are utilized in the production of bolus, which is essential for superficial tumor radiotherapy. This research aimed to compare the variations in dose deposition in deep tissues during electron beam radiotherapy when employing different bolus materials. Specifically, the study developed general superficial tumor models (S-T models) and postoperative breast cancer models (P-B models). Each model comprised a bolus made of water, polylactic acid (PLA), polystyrene, silica-gel or glycerol. Geant4 was employed to simulate the transportation of electron beams within the studied models, enabling the acquisition of dose distributions along the central axis of the field. A comparison was conducted to assess the dose distributions in deep tissues. In regions where the percentage depth dose (PDD) decreases rapidly, the relative doses (RDs) in the S-T models with silica-gel bolus exhibited the highest values. Subsequently, RDs for PLA, glycerol and polystyrene boluses followed in descending order. Notably, the RDs for glycerol and polystyrene boluses were consistently below 1. Within the P-B models, RDs for all four bolus materials are consistently below 1. Among them, the smallest RDs are observed with the glycerol bolus, followed by silica-gel, PLA and polystyrene bolus in ascending order. As PDDs are ~1-3% or smaller, the differences in RDs diminish rapidly until are only around 10%. For the S-T and P-B models, polystyrene and glycerol are the most suitable bolus materials, respectively. The choice of appropriate bolus materials, tailored to the specific treatment scenario, holds significant importance in safeguarding deep tissues during radiotherapy.

Effect of Pulmonary Rehabilitation Exercise on Lung Volume and Respiratory Muscle Recovery in Lung Cancer Patients Undergoing Lobectomy.

Objective: This work assessed the impact of drug therapy combined with pulmonary rehabilitation exercise training on specific lung function and respiratory parameters of lung cancer (LC) patients after thoracoscopic lobectomy. Methods: 88 LC patients who had undergone thoracoscopic lobectomy were selected based on their surgical indications and health condition. The study aimed to explore methods to assist patients in their postoperative recovery; therefore, patients meeting the surgical criteria were chosen to ensure the internal validity and external applicability of the results. Meanwhile, these 88 LC patients undergoing thoracoscopic lobectomy were randomly allocated into an experimental group (EG, 44 cases) and a control group (CG, 44 cases). The EG received inhalation therapy with albuterol sulfate nebulizer solution and personalized pulmonary rehabilitation exercise training, while the CG received nebulized treatment alone. The study lasted for three months. The pulmonary rehabilitation program included regular physical exercises, including respiratory training and physical fitness training, among other activities. Results: After pulmonary lobectomy surgery, both groups of patients showed a significant decrease in (1) forced vital capacity (FVC), (2) forced expiratory volume in 1 second (FEV1), (3) maximum voluntary ventilation (MVV), and (4) peak expiratory flow (PEF). However, the values of FVC, FEV1, MVV, and PEF in the EG were significantly higher than those in the CG (P < .05). Furthermore, both groups demonstrated significant improvements in the 6-minute walk test (6MWT) results after lung lobectomy; however, the 6MWT results in the EG also significantly increased (P < .05). In terms of dyspnea index (DI), after lung lobectomy, the DI for both groups of patients significantly increased, but the DI in the EG was significantly lower than that in the CG (P < .05). Conclusions: The combined application of drug therapy and pulmonary rehabilitation exercise training contributed to promoting cardiopulmonary function and respiratory muscle recovery in LC patients after thoracoscopic lobectomy. This was crucial for improving the quality of life of patients, as enhanced cardiopulmonary function and respiratory muscle recovery can alleviate postoperative respiratory difficulties, increase the physical stamina and activity levels of patients. This may help reduce the risk of postoperative complications, shorten hospital stays, and potentially improve long-term survival rates. Consequently, these results could have a positive impact on the development of postoperative care and treatment strategies. However, this work was subjected to several limitations, including a relatively short duration, necessitating longer-term follow-up to assess long-term effects. Additionally, the sample size was relatively small, and further large-scale research was needed to validate these findings.

Involvement of RFC3 in tamoxifen resistance in ER-positive breast cancer through the cell cycle.

Since the establishment of the molecular subtyping system, ER positive breast cancer was considered to be the most prevalent type of breast cancer, and endocrine therapy was a very important solution. However, numerous studies have shown that the cell cycle plays a key role in the progression and metastasis of breast cancer. The present study showed that RFC3 was involved in the cell cycle through DNA replication. Furthermore, RFC3 expression was significantly higher in breast cancer-resistant cells than in parental cells, which correlated with the cell cycle. We confirmed these results by established drug-resistant cell lines for breast cancer, raw letter analysis and immunohistochemical analysis of primary and recurrent tissues from three ER+ breast cancers. In addition, analysis of the results through an online database revealed that RFC3 expression was significantly associated with poor prognosis in ER+ breast cancer. We also demonstrated that in ER positive breast cancer-resistant cells, knockdown of RFC3 blocked the S-phase of cells and significantly attenuated cell proliferation, migration and invasion. Furthermore, RFC3 overexpression in ER positive breast cancer cells enhanced cell proliferation, migration and invasion. Taking all these findings into account, we could conclude that RFC3 was involved in endocrine resistance in breast cancer through the cell cycle. Thus, RFC3 may be a target to address endocrine therapy resistance in ER positive breast cancer and may be an independent prognostic factor in ER positive breast cancer.

Engineering of a Substrate Affinity Reduced S-Adenosyl-methionine Synthetase as a Novel Biosensor for Growth-Coupling Selection of L-Methionine Overproducers.

Biosensors are powerful tools for monitoring specific metabolites or controlling metabolic flux towards the products in a single cell, which play important roles in microbial cell factory construction. Despite their potential role in metabolic flux monitoring, the development of biosensors for small molecules is still limited. Reported biosensors often exhibit bottlenecks of poor specificity and a narrow dynamic range. Moreover, fine-tuning the substrate binding affinity of a crucial enzyme can decrease its catalytic activity, which ultimately results in the repression of the corresponding essential metabolite biosynthesis and impairs cell growth. However, increasing intracellular substrate concentration can elevate the availability of the essential metabolite and may lead to restore cellular growth. Herein, a new strategy was proposed for constructing whole-cell biosensors based on enzyme encoded by essential gene that offer inherent specificity and universality. Specifically, S-adenosyl-methionine synthetase (MetK) in E. coli was chosen as the crucial enzyme, and a series of MetK variants were identified that were sensitive to L-methionine concentration. This occurrence enabled the engineered cell to sense L-methionine and exhibit L-methionine dose-dependent cell growth. To improve the biosensor's dynamic range, an S-adenosyl-methionine catabolic enzyme was overexpressed to reduce the intracellular availability of S-adenosyl-methionine. The resulting whole-cell biosensor effectively coupled the intracellular concentration of L-methionine with growth and was successfully applied to select strains with enhanced L-methionine biosynthesis from random mutagenesis libraries. Overall, our study presents a universal strategy for designing and constructing growth-coupled biosensors based on crucial enzyme, which can be applied to select strains overproducing high value-added metabolites in cellular metabolism.

Lifestyle improvement and the reduced risk of cardiovascular disease: the China-PAR project.

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS: Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

Angioplasty Guidewire-Assisted vs. Conventional Transseptal Puncture for Left Atrial Appendage Occlusion: a multicentre randomized controlled trial.

AIMS: This study was performed to compare the usability, efficiency, and safety of a modified angioplasty guidewire-assisted transseptal puncture (TSP) technique vs. the conventional approach in facilitating access into the left atrium during left atrial appendage occlusion (LAAO) procedures for the treatment of atrial fibrillation. METHODS AND RESULTS: The ADVANCE-LAAO trial (Angioplasty Guidewire-Assisted vs. Conventional Transseptal Puncture for Left Atrial Appendage Occlusion) was an investigator-initiated, prospective, multicentre, randomized controlled trial (NCT05125159). Patients with atrial fibrillation who underwent LAAO were prospectively enrolled from four centres and randomly assigned to an angioplasty guidewire-assisted TSP group (n = 131) or to a conventional Brockenbrough needle TSP group (n = 132). The primary endpoint was the one-time success rate of TSP. We also analysed the TSP procedure time, failure rate of the assigned TSP type, radiation dose, contrast dose, and procedural complications in both groups. All patients in the guidewire-assisted group underwent successful TSP, whereas five in the standard conventional group switched to the guidewire-assisted approach. The guidewire-assisted puncture improved the one-time success rate (92.4 vs. 77.3%, P = 0.001), shortened the TSP procedure time (109.2 ± 48.2 vs. 120.5 ± 57.6 s, P = 0.023), and tended to have a higher rate of good coaxial orientation of the sheath with the left atrial appendage during the LAAO procedure (66.4 vs. 54.5%, P = 0.059). No TSP-related complications occurred in the guidewire-assisted TSP group, whereas two complications occurred in the conventional TSP group. There was no significant difference in the failure rate of the assigned TSP type, the total procedure time, the total radiation dose, the rate of successful LAAO implantation, or the procedural complication rate between the two groups (all P > 0.05). CONCLUSION: This study confirmed that angioplasty guidewire-assisted puncture can effectively improve the success rate of TSP during LAAO procedures. This novel technique has high potential for application in interventional therapies requiring TSP.

Influence of Heat Treatment on Tea Polyphenols and Their Impact on Improving Heat Tolerance in Drosophila melanogaster.

This study investigated the potential mechanism of action of tea polyphenols (TPs), one of the major active ingredients in tea, to enhance heat resistance in Drosophila and the attenuating effect of heat treatment of TPs on their efficacy. The results showed that TPs were able to prolong the average survival time of Drosophila under high-temperature stress (p < 0.05), but the effect of TPs in prolonging the survival time of Drosophila melanogaster was significantly reduced (p < 0.05) with increasing TP heat-treatment time until it disappeared. The composition of TPs changed after heat treatment. It was also shown that the weakening of the effect of TPs in improving the heat tolerance of Drosophila was related to the decrease in the content of catechins and phenolic acids in their fractions as well as with the increase in the content of laccase. Transcriptomic analysis showed that the effect of TPs on heat tolerance in Drosophila melanogaster was closely related to the longevity regulation pathway, the neuroactive ligand-receptor interaction signaling pathway, and the drug metabolism-cytochrome P450 pathway. Metabolomics analysis showed that the effect of TP intervention in improving the body's heat tolerance was mainly related to amino acid metabolism and energy metabolism. However, thermal processing weakened the relevance of these transcriptomes and metabolomes. The present study reveals the mechanism of action by which heat-treated TPs affect the body's heat tolerance, which is important for the development and utilization of the heat-protection function of tea.

Porous SiO2-Based Reactor with Self-Supply of O2 and H2O2 for Synergistic Photo-Thermal/Photodynamic Therapy.

Purpose: Although the combined photo-thermal (PTT) and photodynamic therapy (PDT) of tumors have demonstrated promise as effective cancer therapy, the hypoxic and insufficient H2O2 supply of tumors seriously limits the efficacy of PDT, and the acidic environment reduces the catalytic activity of nanomaterial in the tumor microenvironment. To develop a platform for efficiently addressing these challenges, we constructed a nanomaterial of Aptamer@dox/GOD-MnO2-SiO2@HGNs-Fc@Ce6 (AMS) for combination tumor therapy. The treatment effects of AMS were evaluated both in vitro and in vivo. Methods: In this work, Ce6 and hemin were loaded on graphene (GO) through π-π conjugation, and Fc was connected to GO via amide bond. The HGNs-Fc@Ce6 was loaded into SiO2, and coated with dopamine. Then, MnO2 was modified on the SiO2. Finally, AS1411-aptamer@dox and GOD were fixed to gain AMS. We characterized the morphology, size, and zeta potential of AMS. The oxygen and reactive oxygen species (ROS) production properties of AMS were analyzed. The cytotoxicity of AMS was detected by MTT and calcein-AM/PI assays. The apoptosis of AMS to a tumor cell was estimated with a JC-1 probe, and the ROS level was detected with a 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) probe. The anticancer efficacy in vivo was analyzed by the changes in the tumor size in different treatment groups. Results: AMS was targeted to the tumor cell and released doxorubicin. It decomposed glucose to produce H2O2 in the GOD-mediated reaction. The generated sufficient H2O2 was catalyzed by MnO2 and HGNs-Fc@Ce6 to produce O2 and free radicals (•OH), respectively. The increased oxygen content improved the hypoxic environment of the tumor and effectively reduced the resistance to PDT. The generated •OH enhanced the ROS treatment. Moreover, AMS depicted a good photo-thermal effect. Conclusion: The results revealed that AMS had an excellent enhanced therapy effect by combining synergistic PTT and PDT.

Severe and fatal adverse events of immune checkpoint inhibitor combination therapy in patients with metastatic renal cell carcinoma: a systematic review and meta-analysis.

Introduction: Immune checkpoint inhibitor (ICI) combination therapy has changed the treatment landscape for metastatic renal cell carcinoma (mRCC). However, little evidence exists on the treatment-related severe adverse events (SAEs) and fatal adverse events (FAEs) of ICI combination therapy in mRCC. Method: We searched PubMed, Embase, and Cochrane Library databases to evaluate randomized controlled trials (RCTs) of ICI combination therapy versus conventional tyrosine kinase inhibitor (TKI)-targeted therapy in mRCC. Data on SAEs and FAEs were analyzed using revman5.4 software. Results: Eight RCTs (n=5380) were identified. The analysis showed no differences in SAEs (60.5% vs. 64.5%) and FAEs (1.2% vs. 0.8%) between the ICI and TKI groups (odds ratio [OR], 0.83; 95%CI 0.58-1.19, p=0.300 and OR, 1.54; 95%CI 0.89-2.69, p=0.120, respectively). ICI-combination therapy was associated with less risk of hematotoxicities, including anemia (OR, 0.24, 95%CI 0.15-0.38, p<0.001), neutropenia (OR, 0.07, 95%CI 0.03-0.14, p<0.001), and thrombocytopenia (OR, 0.05, 95%CI 0.02-0.12, p<0.001), but with increased risks of hepatotoxicities (ALT increase [OR, 3.39, 95%CI 2.39-4.81, p<0.001] and AST increase [OR, 2.71, 95%CI 1.81-4.07, p<0.001]), gastrointestinal toxicities (amylase level increase [OR, 2.32, 95%CI 1.33-4.05, p=0.003] and decreased appetite [OR, 1.77, 95%CI 1.08-2.92, p=0.020]), endocrine toxicity (adrenal insufficiency [OR, 11.27, 95%CI 1.55-81.87, p=0.020]) and nephrotoxicity of proteinuria (OR, 2.21, 95%CI 1.06-4.61, p=0.030). Conclusions: Compared with TKI, ICI combination therapy has less hematotoxicity in mRCC but more specific hepatotoxicity, gastrointestinal toxicity, endocrine toxicity, and nephrotoxicity, with a similar severe toxicity profile. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023412669.

TBX18 knockdown sensitizes esophageal squamous cell carcinoma to radiotherapy by blocking the CHN1/RhoA axis.

OBJECTIVE: Radioresistance is a challenge in the effective treatment of esophageal squamous cell carcinoma (ESCC). Herein, this research ascertained whether TBX18 reduced the radiosensitivity of ESCC. METHODS: Bioinformatics analysis was utilized to retrieve differentially expressed genes. Then, the expression of corresponding candidate genes was tested using qRT-PCR in ESCC clinical specimens, and TBX18 was selected for subsequent experiments. The binding between TBX18 and CHN1 was evaluated by dual-luciferase reporter and ChIP assays, and the relationship between CHN1 and RhoA was identified by GST pull-down. Ectopic expression or knockdown experiments and radiation treatment were performed in cells and the nude mouse xenograft model to clarify the impacts of TBX18, CHN1, and RhoA on radiosensitivity in ESCC. RESULTS: Bioinformatics analysis and qRT-PCR retrieved upregulated TBX18 in ESCC for the follow-up study. Additionally, TBX18 was positively correlated with CHN1 in ESCC clinical specimens. Mechanistically, TBX18 bound to the CHN1 promoter region to transcriptionally activate CHN1, thus elevating RhoA activity. Moreover, TBX18 knockdown reduced ESCC cell proliferation and migration while augmenting their apoptosis after radiation, which was negated by further overexpressing CHN1 or RhoA. CHN1 or RhoA knockdown diminished ESCC cell proliferation and migration, as well as enhanced cell apoptosis, subsequent to radiation. Likewise, TBX18 overexpression increased ESCC cell autophagy after radiation, which was partially reversed by knockdown of RhoA. The results of in vivo xenograft experiments in nude mice were concurrent with the in vitro results. CONCLUSION: TBX18 knockdown lowered CHN1 transcription and thus reduced RhoA activity, which sensitized ESCC cells to radiotherapy.

The Effect of Different Doses of Ciprofol in Patients with Painless Gastrointestinal Endoscopy.

Background: Ciprofol is currently used for painless gastrointestinal endoscopy and anesthesia induction. However, whether it is superior to propofol and its optimal dose remains unknown. Methods: A total of 149 patients, 63 males and 86 females, aged 18-80 years, BMI 18-28 kg/m2, ASA I-III, were divided randomly into four groups: propofol group (group P, n = 44), ciprofol 0.2mg/kg group (group C2, n = 38), ciprofol 0.3mg/kg group (group C3, n = 36) and ciprofol 0.4 mg/kg group (group C4, n = 31). Groups C2, C3 and C4 had injected IV with ciprofol 0.2, 0.3 and 0.4 mg/kg, respectively. Group P had injected IV with propofol 1.5mg/kg. The time for disappearance of the eyelash reflex, gastrointestinal endoscopy time, recovery time, and the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score at awakening (T1), 15 minutes after awakening (T2) and 30 minutes after awakening (T3) were recorded. Results: Compared with group P, the time to fall asleep was significantly shortened, and the incidence of nausea and vomiting and injection pain was significantly lower in groups C2, C3 and C4 (P < 0.05). There was no significant difference in recovery time and recovery quality between each group (P > 0.05). Compared with group P and C4, the incidence of hypotension and respiratory depression was significantly lower in groups C2 and C3 (P < 0.05). Conclusion: The appropriate dose of ciprofol for painless gastrointestinal endoscopy is more advantageous than propofol in hemodynamics and respiratory stability, with less injection pain and nausea and vomiting, which is worthy of clinical promotion.

Zn-Co metal organic frameworks coated with chitosand and Au nanoparticles for chemo-photothermal-targeted combination therapy of liver cancer.

The toxic effects of chemotherapy drugs on normal tissues are still a major limiting factor in cancer treatment. In this paper, we report a metal-organic framework (Zn-Co ZIF) with chitosan-coated outer layer as a carrier for the drug adriamycin hydrochloride (DOX), a treatment for liver cancer, as a novel anti-cancer nanodrug-enhanced carrier. Gold nanoparticles, a good photothermal conversion agent, were combined with the target SH-RGD during surface functionalisation to prepare Zn-Co ZIF@DOX-CS-Au-RGD (ZD-CAR), a nanoplatform with good photothermal conversion properties and targeting for combined liver cancer therapy. ZD-CAR was developed after RGD accurately targeted the tumour and entered the tumour microenvironment (TME), it cleaves and releases the liver cancer therapeutic agent (DOX) in a weak acidic environment to effectively kill tumour cells. The metal skeleton cleavage releases Co2+, which catalyzes the production of oxygen from H2O2 to alleviate the tumour hypoxic environment. The dissolved oxygen could reach 14 mg/L after adding 80 mg/mL of ZD-CAR. Meanwhile, gold nanoparticles could convert light energy into heat energy under 808 NIR irradiation to induce local superheating and kill tumour cells. In summary, this study developed a nanoplatform that combines chemo-photothermal-targeted therapy. It has shown good therapeutic effeciency in cellular experiments and performance tests and has promising applications in anti-cancer therapy.