Latest ArticlesAIM To evaluate the efficacy and safety of oxycodone in acute heart failure （AHF）. METHODS In this prospective randomized controlled trial, 50 AHF patients admitted to the ICU between January 2022 and December 2023 were allocated to morphine group （n=25） or oxycodone group （n=25） using random number table, received intravenous injection of 5 mg morphine or oxycodone based non-invasive ventilation, respectively. Effectiveness outcomes （comfort score,NT-proBNP, oxygenation index （OI）, ICU length of stay, non-invasive ventilation duration, and hospitalization outcomes）and safety parameters （mean arterial pressure （MAP）, heart rate （HR）, respiratory rate （RR）, minute ventilation （MV）,intubation rate, and respiratory depression） were assessed at baseline （T0）, 10 min （T1）, 20 min （T2）, 30 min （T3）,and 24 h （T4） post-treatment in the two groups. RESULTS Both groups showed significant reduction in comfort scores at T3 and increased OI at T4 compared with those of T0 （P<0.01）, and the oxycodone group demonstrated significantly lower NT-proBNP at T4 （P<0.05）, with no significant differences between the two groups（P>0.05）. No between-group differences were observed in ICU stay or ventilation duration. MAP decreased transiently in both groups: the morphine group maintained lower MAP in T1-T3 than T0（P<0.05）, whereas the oxycodone group only showed reductions at T1 and T2 （P<0.05）,with significantly higher MAP than the morphine group during T1-T3 （P<0.05）. HR exhibited biphasic changes while RR and MV progressively declined. The morphine group showed sustained RR reduction in T1-T3 than T0（P<0.05）, and the oxycodone group showed reduction at T2 and T3 （P<0.05）. Neither group required intubation or developed respiratory depression. CONCLUSION Oxycodone demonstrates favorable hemodynamic stability and potential prognostic benefits in AHF management, suggesting its promise as a novel therapeutic option.
N6-methyladenosine（m6A） methylation is involved in the whole process of mRNA biological behavior and plays an important role in the malignant progression of cancer. This article reviewed the invasion and metastasis of m6A methylation in hepatocellular carcinoma （HCC）, its regulation with non-coding RNA, and the effect of immunotherapy. It is very important to find that m6A methylated regulatory proteins are involved in the development and prognosis of HCC.m6A methylation is closely related to the regulation of non-coding RNA on the proliferation, metastasis and drug resistance of HCC. In terms of immunotherapy, circRHBDD1 and BTBD10 participate in m6A methylation modification to regulate cell metabolism and inhibit the immune escape of cancer cells, which can be used for the HCC diagnosis and innovative drug discovery in the future.
To investigate the role of miR-17-5p in mediating cisplatin（DDP）resistance in breast cancer cells by regulating the PTEN/Akt pathway.
MCF-7/DDP-resistant cell line was cultured with a gradient of increasing DDP concentrations. The content of miR-17-5p was detected in MCF-7 and MCF-7/DDP cells by RT-qPCR. MCF-7 cells were divided into miR-NC and miR-17-5p groups, and transfected with miR-NC and miR-17-5p mimics plasmids,respectively. MCF-7/DDP-resistant cells were divided into anti-miR-NC and anti-miR-17-5p groups, and transfected with anti-miR-NC and anti-miR-17-5p plasmids, respectively. Transfection efficiency was defined by RT-qPCR. The drug sensitivity of DDP in each group of transfected cells was evaluated by MTT. The direct effect of miR-17-5p on the invasive ability was obtained by Transwell assay. DDP-induced apoptosis of MCF-7 and MCF-7/DDP cells after transfection was analyzed by flow cytometry. The targeting relationship between miR-17-5p and PTEN was verified by double luciferase reporter gene assay. The changes of apoptosis and key proteins of PTEN/Akt pathway under the regulation of miR-17-5p were detected by Western blot.
Compared with MCF-7 cells, the miR-17-5p expression in MCF-7/DDP-resistant cells was abnormally increased, while the PTEN expression was reduced（P<0.01）. PTEN was regulated by miR-17-5p as a target gene. Compared with the miR-NC group, the proliferation inhibition rate in the miR-17-5p mimics group was significantly declined, the number of invaded cells was enhanced, and the apoptosis rate was also decreased（P<0.05）, and the expressions of tumor suppressor proteins PTEN, p21 and p27 in the PTEN/Akt pathway were decreased, and the expressions of p-Akt308, p-Akt473 and cyclin D1 were increased（P<0.01）. Compared with the anti-miR-NC group, the proliferation inhibition rate was increased in the anti-miR-17-5p group, the number of invaded cells was decreased, and the apoptosis rate was also increased（P<0.05）, and the expression of tumor suppressor proteins PTEN, p21 and p27 was increased, and the expression of p-Akt308, p-Akt473 and cyclin D1 was decreased（P<0.01）.
Knockdown of miR-17-5p can effectively improve the DDP sensitivity of breast cancer cells, attenuate the invasive ability, and induce further apoptosis,which may be related to the regulatory effect of miR-17-5p on the PTEN/Akt pathway.
Chinese materia medica genetic resources are important biological and health resources. With the increasing reliance on Chinese materia medica genetic resources in various fields, bio-piracy against Chinese materia medica genetic resources is becoming more and more frequent and has posed a threat to China’s ecological security and the rights of people’s lives and health. However, the system of the source disclosure of genetic resources established by China’s Patent Law, as well as the use of contractual mechanisms to achieve access to Chinese materia medica genetic resources and benefit-sharing, are both inadequate and unable to effectively deal with the problem of bio-piracy. Therefore, in order to safeguard the rights and interests，China, as a party to the Convention on Biological Diversity and the Nagoya Protocol, should formulate or improve the domestic laws following the legal rules established by the above-mentioned international treaties and China’s national conditions. Related initiatives may include taking the source disclosure as a formal condition for the patent grant, expanding the target and scope of the disclosure, and imposing legal liability for defect disclosure; clarifying the subjects of rights to Chinese materia medica genetic resources, and introducing public authority to “monitor” the signing and implementation of contracts to ensure fair and equitable benefit-sharing.
The Inflation Reduction Act（IRA）took effect in the United States in 2022. For the first time, the IRA allows the federal government to negotiate prescription drug prices, requires pharmaceutical companies to pay rebates to Medicare when prices rise above the rate of inflation, caps patient out-of-pocket costs for Medicare Part D drugs and insulin products, continues the “safe harbor” policy, extends the advance premium tax credit policy, and expands the types of free vaccinations. The IRA has multiple impacts on Medicare drug spending, but it still faces structural pressure in terms of price control. It is suggested that China can continue to utilize the public welfare advantages of basic medical and healthcare services, improve the targeting and operability of relevant health policies,and protect innovation while controlling drug prices.
To explore the effects of esmolol on hemodynamics and inflammatory reaction during endoscopic sinus surgery in patients with sinusitis.
Eighty patients with sinusitis undergoing endoscopic sinus surgery were randomly divided into control group and trial group, with 40 patients in each group. The control group received routine anesthesia induction and maintenance, while the trial group received an additional 0.5 mg·kg-1 of esmolol injection during anesthesia induction and 30 μg·kg-1·min-1 of esmolol pump injection during anesthesia maintenance. The blood pressure and heart rate of patients were observed, the levels of interleukin（IL）-6, tumor necrosis factor（TNF）-α and C-reactive protein（CRP）in the blood were detected, and the recovery time, intraoperative blood loss, propofol dosage, remifentanil dosage and postoperative nausea and vomiting rate were compared between the two groups.
The systolic blood pressure, diastolic blood pressure, and heart rate of the trial group were lower than those in the control group at entering the operating room, the time of tracheal intubation, the beginning of surgery, 1 h after the beginning of surgery（T3）, the end of surgery（T4）, and the time of tracheal intubation was removed（P<0.01）. The levels of IL-6, TNF-α and CRP at T3 and T4 in the trial group were also lower than those in the control group（P<0.01）. The recovery time of the trial group was significantly shorter than that of the control group（P<0.01）, and the amount of intraoperative blood loss, propofol and remifentanil was significantly lower than that of the control group（P<0.01）. The incidence of postoperative nausea and vomiting in the trial group was lower than that in the control group（P<0.05）.
Esmolol is beneficial to maintain the stable hemodynamics of patients with sinusitis during endoscopic sinus surgery, can reduce inflammatory reaction, reduce intraoperative blood loss and the dosage of general anesthetics, and is relatively safe.
Acne vulgaris is one of the most common skin diseases in dermatology. Retinoids are commonly used in the treatment of this disease. Trifarotene is derived from CD437, a triaryl skeleton lead compound with retinoic acid receptor subtype selectivity, after the optimization of receptor structure. It is called the fourth generation retinoic acid anti-acne drug because of its high selectivity for retinoic acid γ receptor（RAR-γ）. In October 2019, trifarotene was approved by the U.S.Food and Drug Administration for the treatment of acne vulgaris in patients aged 9 and above. Clinical trials have shown that trifarotene is safe, effective and well tolerated in the treatment of acne vulgaris, which has a good clinical application prospect.
Chimeric antigen receptor（CAR）- T cell therapy has changed the traditional treatment of hematological malignancies and has shown significant efficacy. However, the clinical application of CAR-T cells is limited by long production cycle, high price, and side effects such as cytokine storm, so it can not be widely used in clinical practice. Natural killer（NK）cells are an important part of the body’s innate immune response. Compared with CAR-T cells, CAR-NK cells can significantly reduce the probability of neurotoxicity, cytokine storm, and graft versus host diseases. CAR-NK cell therapy is gradually becoming a research hotspot, but there are still some urgent problems to be solved, and further optimization of the construction strategy is needed to achieve its clinical translation. This paper will review the construction strategy and the research progress in tumor immunotherapy based on the latest literatures at home and abroad, in order to provide valuable reference for application of NK cells in the treatment of malignant tumors.
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