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Purpose This multicenter Phase II clinical study assessed the efficacy and safety of hypofractionated radiotherapy (HFRT) in combination with a PD-1 inhibitor, granulocyte macrophage-colony stimulating factor (GM-CSF), and thymosin-α1 in patients with heavily treated metastatic solid tumors. Methods Patients were enrolled between September 2022 and May 2024. HFRT was administered to targeted tumors, and GM-CSF was administered for 14 days from day 1 of radiotherapy. Thymosin-α1 was injected concurrently twice weekly until disease progression. Immunotherapy with camrelizumab was started following HFRT and repeated every 3 weeks. GM-CSF was administered daily for 7 days before each cycle of immunotherapy. Results By June 15, 2024, there were 37 study participants. The median follow-up duration was 5.97 months (range 0.40–20.9). Median progression-free survival was 3.5 months (95% confidence interval 2.73–4.23) in the intention-to-treat population. The objective response rate was 23.08%, and the disease control rate was 65.38%. Overall survival data are not yet mature. Abscopal effects were observed in 6 patients (23.08%); four of whom achieved a partial response. Patients who achieved a partial response were significantly more likely to have an abscopal effect( P  = 0.025). The group with a lower baseline neutrophil–lymphocyte ratio had a significantly lower risks of distant metastasis and death( P = 0.024). Seventeen adverse reactions were reported, including six grade 3 or 4 adverse events. There were no grade 5 adverse events. Conclusion In conclusion, the trends in efficacy observed in our study are promising; however, well-designed protocols are essential to validate these findings.

Urea is a commonly used nitrogen (N) fertilizer that contributes to world food production, and there have been increasing concerns about relatively low urea-N use efficiency. Biochar has shown the potential to mitigate N loss, but how biochar influences urea hydrolysis and the underlying mechanisms are still unclear. In this study, long-term biochar-amended upland, paddy and greenhouse soils were sampled at depths of 0–20 and 20–40 cm in Haicheng City, Northeast China. Soil N contents, urea hydrolysis rates (UHRs), and total, intracellular and extracellular urease activities were determined, as well as the total bacterial and ureolytic microbial gene abundance were quantified. The results showed that biochar increased total urease activity by 32.64–66.39% in upland soil and by 2.90–2.13-fold in paddy soil. Both intracellular and extracellular ureases contributed to the increase in total urease activity. However, in greenhouse soil, extracellular (+35.07–74.22%) and intracellular (−40.14–77.68%) urease activities responded inconsistently to biochar incorporation. Increases in ureC gene copy numbers (2.15- to 4.47-fold) in upland and greenhouse (20.93%) soil implied that biochar stimulated microorganisms capable of producing urease, and the biochar liming effect increased the soil pH (0.11–0.60 units), which optimized the ureolytic reaction, together explained the increases in urease activity. We found that the decreased soil N content was accompanied by a higher UHR in upland and greenhouse soils, suggesting that the accelerated UHR exerted a negative effect on the soil N content, possibly caused by excessive NH 3 volatilization. In paddy soil, where the UHR was not increased, biochar was an effective amendment for simultaneously improving soil urease activity and N content.

Background Recent studies reported that blood-based microRNAs (miRNAs) could detect cancers and predict prognosis have opened a new field of utilizing circulating miRNAs as cancer biomarkers. In this pilot study, we conducted for the first time, to our knowledge, the evaluation of the applicability of salivary miRNAs as novel biomarkers for nasopharyngeal carcinoma (NPC) detection. Methods Microarray miRNA expression profiling was performed on saliva samples from 22 newly diagnosed NPC patients and 25 healthy controls, and 12 significantly down-regulated miRNAs were selected for quantitative real-time-PCR (qRT-PCR) validation and further analysis. Their target genes enriched by gene ontology and pathway analysis were used to construct regulatory and interaction networks. The receiver operating characteristic analyses (ROC) and logistic regression were calculated to assess discriminatory accuracy. Results Twelve dysregulated miRNAs screened by microarray that showed the same expression patterns with qRT-PCR analysis. Through bioinformatics analysis, the most prominent hub gene probably regulated by the 12 down-regulated miRNAs is found to be TP53. The ROC including the 12 miRNAs separated NPC patients from healthy controls with very high accuracy (areas under the receiver operating characteristic curve [AUC] = 0.999, sensitivity = 100.00%, specificity = 96.00%). Furthermore, if only six significantly dysregulated miRNAs were selected for the ROC analysis, the accuracy is still impressive (AUC = 0.941, sensitivity = 95.45%, specificity = 80.00%). Conclusions This study highlights the potential for salivary miRNAs as biomarkers for the detection of NPC. Meanwhile, differentially expressed miRNAs in saliva might play critical roles in NPC by regulating their target genes, which associated with some significant pathways, such as p53 signaling pathway.

HR18034, composed of the ropivacaine encapsulated in multi-lamellar, concentric circular structure liposomes as the major component and a small amount of free ropivacaine, has performed well in animal experiments and phase I clinical trials. This trial was to investigate the efficacy, safety, pharmacokinetic profile and the minimum effective dose of HR18034 for postoperative analgesia after hemorrhoidectomy compared with ropivacaine. A multicenter, randomized, double-blind trial. 19 medical centers in China. 85 patients undergoing hemorrhoidectomy between October 2022 to November 2022. Patients were randomly divided into HR 18034 190 mg group, 285 mg group, 380 mg group and ropivacaine 75 mg group, receiving single local anesthetic perianal injection for postoperative analgesia. The primary outcome was the area under the resting state NRS score -time curve within 72 h after injection. The second outcomes included the proportion of patients without pain, the proportion of patients not requiring rescue analgesia, cumulative morphine consumption for rescue analgesia, etc. Safety was evaluated by adverse events incidence and plasma ropivacaine concentrations were measured to explore the pharmacokinetic characteristics of HR18034. The areas under the NRS score (at rest and moving states)-time curve were significantly lower in HR 18034 380 mg group than ropivacaine 75 mg at 24 h, 48 h, and 72 h after administration. However, this superiority was not observed in HR18034 190 mg group and 285 mg group. There was no difference in cumulative morphine consumption for rescue analgesia between HR 18034 groups and ropivacaine group. HR 18034 380 mg showed superior analgesic efficacy and equivalent safety compared to ropivacaine 75 mg after hemorrhoidectomy, thus preliminarily determined as minimum effective dose. HR 18034 380 mg showed superior analgesic efficacy (lower area under the resting and moving states NRS score-time curve, The higher proportion of patients free of pain) and equivalent safety compared to ropivacaine 75 mg after hemorrhoidectomy, thus preliminarily determined as minimum effective dose. [Display omitted] •Few clinical studies have been conducted on liposomal ropivacaine. No randomized controlled trial of perianal injection, local infiltration anesthesia for post-hemorrhoidectomy analgesia has been reported.•Consisted of a small fraction of free ropivacaine and a predominant portion of ropivacaine encapsulated by multi-layered concentric circular liposome, HR 18034 has an innovative structure, providing rapid pain relief of operative incision through free ropivacaine and sustained analgesia via slow release of the encapsulated ropivacaine from the liposome.•In addition to evaluating the safety and efficacy of the drug, the pharmacokinetic characteristics of the HR 18034 were reported in this study to further guide the clinical applications.

Substituting chemical fertilizers with organic alternatives represents an effective strategy for mitigating soil nitrogen (N) loss and reducing chemical fertilizer use. However, the efficacy of organic substitution in regulating soil N fertility and rice growth requires further investigation, and mechanistic studies elucidating how organic fertilizers affect soil N transformation processes and availability are still deficient. To address this, we conducted a three-year field experiment from 2021 to 2023, comparing three rice fertilization regimes: (1) chemical fertilizer as the control (CK), (2) substitution with organic fertilizer (OF), and (3) substitution with biochar-based organic fertilizer (BF). Both organic substitution treatments were applied as basal fertilizer, and the rice plants received equivalent topdressing applications. The soil N availability, gross and net N transformation rates, and soil microbial activity were analyzed, and the rice growth index and yield were determined. The results showed that organic substitution (OF and BF) significantly increased the soil total carbon content, stimulated microbial biomass growth and enhanced enzymatic activity associated with soil C and N cycling. However, the limited N input from organic substitution significantly decreased the soil gross N mineralization rate by 28.30% (OF) and 58.14% (BF), compared to chemical fertilization (CK). It also reduced the gross N nitrification rate by 38.30% (OF) and 36.17% (BF). These suppressed N transformation processes ultimately led to 11.97% (OF) and 14.72% (BF) lower soil mineral N contents. The soil N deficiency during critical early vegetative growth stages substantially constrained rice development, resulting in significant yield reductions in the OF and BF treatments compared to chemical fertilization (CK). These results indicate that complete organic substitution compromises rice yields due to insufficient N availability; therefore, we recommend integrated organic–mineral fertilization as an optimal strategy to achieve both crop productivity and environmental benefits.

Mobile Internet has changed the way of information acquisition and dissemination, which also brings new challenges to the teaching of Higher Vocational colleges. Teachers must keep up with the development of technology. By understanding the new needs of College students, teachers can reform the teaching content, teaching methods, teaching design and so on. Through the teaching reform, vocational colleges can cultivate comprehensive applied talents adapted to the mobile internet. This paper first analyses the significance of higher vocational education reform under the background of mobile internet. Then, this paper analyses the problems existing in the teaching of Higher Vocational Colleges in the era of mobile internet. Finally, some suggestions are put forward.

Background This study aimed to compare the efficacy and toxicity of raltitrexed (Saiweijian®) plus cisplatin (SP regimen) and 5‐fluorouracil plus cisplatin (FP regimen) as concurrent chemoradiotherapy (CCRT) in patients with locally advanced nasopharyngeal carcinoma (LA‐NPC). Methods Eligible patients (N = 135) were allocated randomly in a ratio of 1:1 to receive CCRT with either SP or FP. At least 2 cycles of chemotherapy was administrated during radiotherapy. Progression free survival (PFS) was primary endpoint. Secondary endpoints included overall survival (OS), loco‐regional relapse free survival (LRRFS), distant metastasis free survival (DMFS) and toxicity. Results In this study, 68 patients received SP as CCRT, and 67 received FP. Objective responses were noted in 97.1% of the patients in the SP group and in 97.0% of the patients in the FP group (P = 1.00). At the end of a median 36 months follow‐up period, the estimated 3‐year PFS rates were 70.1% for SP and 66.6% for FP, respectively. The 3‐year LRRFS, DMFS and OS rates were 88.9%, 74.7% and 84.0%, respectively, for the SP group, and 92.3%, 71.0% and 73.7%, respectively, for the FP group. Overall, there was no difference between treatment groups with regard to response or survival. The most frequent acute toxicities monitored in both groups were bone marrow suppression, gastrointestinal side effects and oral mucositis (OM). The overall incidence of grade 3‐4 OM in the FP group (47.8%) was higher than in the SP group (11.8%). However, the incidence of other adverse effects observed in both groups was similar (P > .05). Conclusions These data indicate that SP and FP therapies have similar efficacy in treating LA‐NPC. The SP regimen showed a tolerable safety profile along with a lower frequency of severe OM and therefore, an improved life quality. In conclusion, SP was a well tolerated, effective, regimen for LA‐NPC treatment. The incidence of other adverse effects seen in both groups was similar (P > .05).The efficacy of both regimens i.e. SP and FP are found similar. The SP regimen has tolerable safety profile, with a lower incidence of severe OM and consequently, an improved quality of life.

Abstract Objective To investigate whether perioperative ultrasound-guided serratus anterior plane block (SAPB) combined with general anesthesia is more effective and safer than current analgesic techniques for postoperative analgesia after video-assisted thoracoscopic surgery (VATS). Methods PubMed, the Cochrane Library, and EMBASE were searched for clinical trials published up to July 31, 2019. Outcomes, including operative duration, postoperative pain scores, postoperative analgesia use, patient satisfaction with analgesia, time to chest tube removal, length of stay, and adverse effects were analyzed. Results Four clinical trials, including 262 patients, met inclusion criteria. Ultrasound-guided SAPB reduced pain scores at zero, 15, 30, 45, and 60 minutes in the postoperative anesthesia care unit (all P < 0.05) and at one, two, six, 12, and 24 hours in the ward (all P < 0.001). Additionally, postoperatively, morphine consumption at 15 and 30 minutes, overall morphine consumption, and total consumption (morphine plus tramadol) were significantly lower in the SAPB cohort (P  < 0.05). Similarly, postoperative tramadol consumption at one, two, six, 12, and 24 hours was also lower in this cohort (all P  < 0.05). The postoperative consumption of fentanyl, tramadol, and total morphine in patient-controlled analgesia (PCA) at 24 hours was significantly reduced (P < 0.05). Moreover, SAPB provided better patient satisfaction with analgesia (P = 0.0038). However, no statistically significant difference was found in duration of operation, time to chest tube removal, length of stay, or side effects (all P > 0.05). Conclusions Perioperative ultrasound-guided SAPB combined with general anesthesia provided more effective postoperative analgesia after VATS. However, no significant advantage was found regarding side effects.

Chronic allograft nephropathy (CAN) is a common finding in kidney grafts with functional impairment. Prolonged hypothermic storage–induced ischemia-reperfusion injury is associated with the early onset of CAN. As the noble gas xenon is clinically used as an anesthetic and has renoprotective properties in a rodent model of ischemia-reperfusion injury, we studied whether early treatment with xenon could attenuate CAN associated with prolonged hypothermic storage. Exposure to xenon enhanced the expression of insulin growth factor-1 (IGF-1) and its receptor in human proximal tubular (HK-2) cells, which, in turn, increased cell proliferation. Xenon treatment before or after hypothermia-hypoxia decreased cell apoptosis and cell inflammation after reoxygenation. The xenon-induced HK-2 cell proliferation was abolished by blocking the IGF-1 receptor, mTOR, and HIF-1α individually. In the Fischer-to-Lewis rat allogeneic renal transplantation model, xenon exposure of donors before graft retrieval or recipients after engraftment enhanced tubular cell proliferation and decreased tubular cell death and cell inflammation associated with ischemia-reperfusion injury. Compared with control allografts, xenon treatment significantly suppressed T-cell infiltration and fibrosis, prevented the development of CAN, and improved renal function. Thus, xenon treatment promoted recovery from ischemia-reperfusion injury and reduced susceptibility to the subsequent development of CAN in allografts.

Bone cancer pain is refractory to currently available clinical treatment owing to its complicated underlying mechanisms. Studies found that extracellular matrix molecules can participate in the regulation of chronic pain. Decorin is one of the most abundant extracellular matrix molecules, and the present study evaluated the effect of decorin on the development of bone cancer pain. We found that decorin was upregulated in the L4–L6 spinal dorsal horn of the bone cancer pain rats. Spinal microinjection of a decorin-targeting RNAi lentivirus alleviated bone cancer pain-induced mechanical allodynia and reduced the expression of pGluR1-Ser831 in the bone cancer pain rats. Meanwhile, decorin knockdown impaired the excitatory synaptogenesis in cultured neurons and prevented the clustering and insertion of pGluR1-Ser831 into postsynaptic membranes. Taken together, the results of our study suggested that decorin contributes to the development of bone cancer pain possibly by regulating the activity of excitatory synaptic molecules in the spinal cord. Our findings provide a better understanding of the function of decorin as a possible therapeutic target for alleviating bone cancer pain.