Exogenous leucine alleviates heat stress and improves saponin synthesis in Panax notoginseng by improving antioxidant capacity and maintaining metabolic homeostasis

Panax notoginseng saponins (PNSs) are used as industrial raw materials to produce many drugs to treat cardio-cerebrovascular diseases. However, it is a heat-sensitive plant, and its large-scale artificial cultivation is impeded by high temperature stress, leading to decreases in productivity and PNSs yield. Here, we examined exogenous foliar leucine to alleviate heat stress and explored the underlying mechanism using metabolomics. The results indicated that 3 and 5 mM exogenous foliar leucine significantly alleviated heat stress in one-year- and two-year-old P. notoginseng in pots and field trials. Exogenous foliar leucine enhanced the antioxidant capacity by increasing the activities of antioxidant enzymes (POD, SOD) and the contents of antioxidant metabolites (amino acids). Moreover, exogenous foliar leucine enhanced carbohydrate metabolism, including sugars (sucrose, maltose) and TCA cycle metabolites (citric acid, aconitic acid, succinic acid and fumaric acid), in P. notoginseng leaves, stems, and fibrous roots to improve the energy supply of plants and further alleviate heat stress. Field experiments further verified that exogenous foliar leucine increased the productivity and PNSs accumulation in P. notoginseng. These results suggest that leucine application is beneficial for improving the growth and quality of P. notoginseng under heat stress. It is therefore possible to develop plant growth regulators based on leucine to improve the heat resistance of P. notoginseng and other crops

Protective Effect of RNase on Unilateral Nephrectomy-Induced Postoperative Cognitive Dysfunction in Aged Mice

Postoperative cognitive dysfunction (POCD) is a common complication after surgery, especially for elderly patients. Administration of RNase has been reported to exhibit neuroprotective effects in acute stroke. However, the potential role of RNase on POCD is unknown. Therefore, we sought to investigate whether RNase treatment could mitigate unilateral nephrectomy induced-cognitive deficit in aged mice. In the present study, twelve-month-old mice were administered RNase or an equal amount of normal saline perioperatively. All mice underwent Morris Water Maze (MWM) training 3 times per day for 7 days to acclimatize them to the water maze before surgical operation, and testing on days 1, 3 and 7 after surgery. We found that perioperative administration of RNase: 1) attenuated unilateral nephrectomy-induced cognitive impairment at day 3 after surgery; 2) reduced the hippocampal cytokines mRNA production and serum cytokines protein production at day 1 and day 7 (for MCP-1) after surgery, and; 3) inhibited hippocampal apoptosis as indicated by cleaved caspase-3 western blot and TUNEL staining at day 1 after surgery. In addition, a trend decrease of total serum RNA levels was detected in the RNase treated group after surgery compared with the untreated group. Further, our protocol of RNase administration had no impact on the arterial blood gas analysis right after surgery, kidney function and mortality rate at the observed days postoperatively. In conclusion, perioperative RNase treatment attenuated unilateral nephrectomy-induced cognitive impairment in aged mice

Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies

<p>Abstract</p> <p>Background</p> <p>YN968D1 (Apatinib) selectively inhibits phosphorylation of VEGFR-2 and tumor angiogenesis in mice model. The study was conducted to determine the maximum tolerated dose (MTD), safety profile, pharmacokinetic variables, and antitumor activity in advanced solid malignancies.</p> <p>Methods</p> <p>This dose-escalation study was conducted according to the Chinese State Food and Drug Administration (SFDA) recommendations in patients with advanced solid tumors to determine the MTD for orally administered apatinib. Doses of continuously administered apatinib were escalated from 250 mg. Treatment continued after dose-escalation phase until withdrawal of consent, intolerable toxicities, disease progression or death.</p> <p>Results</p> <p>Forty-six patients were enrolled. Hypertension and hand-foot syndrome were the two dose-limiting toxicities noted at dose level of 1000 mg. MTD was determined to be 850 mg once daily. Pharmacokinetic analysis showed early absorption with a half-life of 9 hours. The mean half-life was constant over all dose groups. Steady-state conditions analysis suggested no accumulation during 56 days of once-daily administration. The most frequently observed drug-related adverse events were hypertension (69.5%, 29 grade 1-2 and 3 grade 3-4), proteinuria (47.8%, 16 grade 1-2 and 6 grade 3-4), and hand-foot syndrome (45.6%, 15 grade 1-2 and 6 grade 3-4). Among the thirty-seven evaluable patients, PR was noted in seven patients (18.9%), SD 24 (64.9%), with a disease control rate of 83.8% at 8 weeks.</p> <p>Conclusions</p> <p>The recommended dose of 750 mg once daily was well tolerated. Encouraging antitumor activity across a broad range of malignancies warrants further evaluation in selected populations.</p> <p>Trial registration</p> <p>ClinicalTrials.gov unique identifier: NCT00633490</p

Attention to pulmonary arteriovenous fistula in a case of transient hypoxemia and cerebral infarction during pregnancy: a case report and literature review

Abstract Background Pulmonary arteriovenous fistula is rare during pregnancy. Pulmonary arteriovenous fistula presents no pulmonary symptoms in most patients but can be exacerbated by pregnancy. If not diagnosed and treated promptly, pulmonary arteriovenous fistula can lead to respiratory failure, stroke, spontaneous hemothorax, or other fatal complications. Case presentation A 29-year-old healthy pregnant woman presented with a transient drop in blood oxygen level of unknown cause during a routine examination at 34 weeks of gestation and during a cesarean section at 38 weeks of pregnancy. The patient’s oxygen saturation quickly returned to normal and was not further investigated. On day 3 postpartum, the patient suddenly displayed slurred speech and right limb myasthenia. A head magnetic resonance imaging revealed cerebral infarction in the left basal ganglia. Subsequent computed tomography pulmonary arteriography revealed bilateral pulmonary arteriovenous fistula, which was likely the cause of cerebral infarction. The patient was transferred to the Department of Thoracic Surgery after one month of treatment and successfully underwent percutaneous embolization of pulmonary arteriovenous fistula. Conclusion Pulmonary arteriovenous fistula should not be neglected if a pregnant woman presents with transient hypoxemia and cerebral infarction. A transient decrease in pulse oxygen saturation that cannot be explained by common clinical causes can be an early warning sign of the disease. Early diagnosis and multidisciplinary management could improve the prognosis

Bilateral thoracic Paravertebral block for immediate postoperative pain relief in the PACU: a prospective, observational study

Abstract Background To investigate the feasibility, effectiveness and safety of bilateral thoracic paravertebral block (TPVB) in the post anesthesia care unit (PACU) for pain relief in participants after laparotomy. Methods A single shot of bilateral TPVB with 25 ml of 0.2% ropivacaine and 5 mg dexamethasone in combination for both sides at the 8th thoracic transverse level (T8) was performed on 201 participants who complained moderate to severe pain on arrival to PACU after laparotomy. The visual analog scale (VAS) pain scores at rest and on cough, heart rate, blood pressure, and pulse oximetry before and after bilateral TPVB for up to 1 h were recorded. The VAS Pain scores at rest and on cough at 24 h after bilateral TPVB were also recorded. Results Bilateral TPVB was carried out successfully in all participants. The VAS pain scores at rest and on cough were 7.9 ± 1.6 and 8.7 ± 1.3 respectively pre-bilateral TPVB. The VAS pain scores at rest and on cough were significantly decreased to 1.1 ± 1.2 and 2.1 ± 1.6 respectively (P < 0.001) at 60 min after bilateral TPVB and to 2.1 ± 1.7 and 3.8 ± 1.9 at rest and on cough respectively ((P < 0.001) at 24 h after bilateral TPVB. At 10 min post-bilateral TPVB, only systolic blood pressure was reduced from 122 ± 19 mmHg to 111 ± 18 mmHg (P = 0.007) but then gradually became stable. No complications related to bilateral TPVB were observed. Conclusion Bilateral TPVB can be provided for pain relief to the participants who suffer from moderate to severe pain after upper laparotomy in the PACU. Trial registration Chinese Clinical Trial Registry: ChiCTR-ONN-16009229 , Registered on 10 September 2016

Pharmacotherapy for improving postoperative sleep quality: a protocol for a systematic review and network meta-analysis

Introduction Improving the quality of sleep may promote enhanced recovery in surgical patients. In addition to controversial or conflicting study conclusions, the current clinical studies on pharmacotherapy for improving postoperative sleep quality are mostly limited to evaluating the effect of a specific drug or supplement compared with placebo, and they lack comparisons between drugs or supplements. Therefore, we plan to conduct a systematic review and network meta-analysis to compare the efficacy of different drugs or supplements for improving postoperative sleep quality.Methods and analysis We will search the MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CNKI and Wanfang databases from the dates of their inception to December 2022. We will only include randomised controlled trials, irrespective of language and publication status. The primary outcome is postoperative sleep quality assessed by any validated tools or polysomnography. We will assess the quality of all included trials according to version 2 of the Cochrane risk-of-bias tool for randomised trials. We will use the GeMTC package of R software to perform direct and indirect comparisons via a Bayesian framework using a random-effects model. We will use the Confidence in Network Meta-Analysis approach to evaluate the quality of evidence.Ethics and dissemination Ethical approval is not required for this protocol because we will only be pooling published data. We plan to submit our review to academic conferences and peer-reviewed academic journals.PROSPERO registration number CRD42022356508