Latest ArticlesN6-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.
AIM To analyze the clinical characteristics and influencing factors of dextromethorphan-induced 5-hydroxytryptamine syndrome (5-HTS). METHODS Relevant cases of dextromethorphan-induced 5-HTS in PubMed,Embase, Cochrane Library, CINAHL, PsycINFO, CNKI, WanFang database, SinoMed, and VIP database were retrieved,and clinical data were summarized and analyzed. RESULTS A total of 16 cases of 5-HTS were collected, including 11 males and 5 females. Dextromethorphan could cause 5-HTS at both normal and excessive doses, and the majority (88%)of patients were co-administered with other 5-hydroxytryptamine drugs. The onset of 5-HTS occurred between 4 hours and 6 weeks after dextromethorphan administration, with symptoms including myoclonus, tachycardia, and fever. After discontinuation of dextromethorphan and other serotonergic drugs, along with supportive therapy, all patients improved.The mean duration of 5-HTS was 26 hours. Patients treated with cyproheptadine had a shorter duration of 5-HTS, averaging 21.6 hours. CONCLUSION Dextromethorphan-induced 5-HTS most often occurs when used in combination with other serotonergic drugs. It is recommended to strengthen management to reduce the abuse of dextromethorphan and unnecessary co-administration, as well as to improve the ability of physicians and pharmacists to recognize and monitor 5-HTS.
Antibody-drug conjugates(ADCs)consist of monoclonal antibodies, linkers, and cytotoxic drugs,representing a novel class of anti-cancer agents that combine target specificity with chemotherapeutic efficacy. ADCs have demonstrated significant efficacy not only in breast cancer, gastric cancer and lung cancer, and have also shown clinical benefits in ovarian cancer. This review discussed the structure, mechanism, and applications of ADCs in ovarian cancer,aiming to provide new insights for clinical treatment of ovarian cancer.
Integrins play an important role in mediating the entry of lymphocytes into the intestines leading to the development of inflammatory bowel disease(IBD), and their binding to the corresponding ligands mediates the intestinal homing and retention of lymphocytes. Currently, the anti-integrin drug vedolizumab has been used in clinical practice, and several other anti-integrin drugs are under development, such as abrilumab, AJM300, PTG-100, and milategrast. Clinical studies have shown that gut-selective anti-integrin agents may be a safe and effective option for the treatment of IBD.
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.
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.
To investigate the effect of ultrasound-guided lateral quadratus lumborum block(QLB-1)on the median effective dosage(ED50)of butorphanol by patient controlled intravenous analgesia(PCIA)performed after cesarean section under general anesthesia.
Parturients were scheduled for cesarean section under general anesthesia,gestation 37-42 weeks, ASA physical status Ⅱ were assigned into two groups, group Q(QLB-1 combined with butorphanol PCIA)and group C(butorphanol PCIA). Each group was expected to have 35 cases. Both groups were administered general anesthesia with endotracheal intubation. The group Q: 0.3% ropivacaine with 25 mL were injected in the QLB-1 in each side respectively under ultrasound guidance before extubation at the end of the surgery. The group C: no nerve block.The two groups underwent PCIA after extubation. The scores of resting visual analogue scale(VAS)≤3 points or VAS of motion state ≤4 points within 48 hours after operation were used as the criteria of analgesia satisfaction. The initial dose of butorphanol with PCIA was 4 μg·kg-1·h-1, adjusted by the modified Dixon’s up-and-down method with a dose gradient of 0.25 μg·kg-1·h-1. Probit analysis was used for calculating ED50 and 95% confidence interval(CI)of butorphanol PCIA for satisfactory analgesia.
The sample size included in group Q and group C were 31 and 28 cases, respectively.The ED50 of butorphanol PCIA for satisfactory analgesia was 3.81 μg·kg-1·h-1 for the group C(95%CI: 2.87 to 4.25 μg·kg-1·h-1)and 2.45 μg·kg-1·h-1 for the group Q(95%CI: 2.16 to 2.70 μg·kg-1·h-1). In the parturients with satisfactory analgesia of the two groups, the incidence of drowsiness, dizziness and nausea was higher in the group C than that in the group Q(P<0.05).
The ED50 of butorphanol PCIA combined with QLB-1 for satisfactory relieve postoperative analgesia after cesarean section under general anesthesia reduce butorphanol PCIA alone by 36% and reduce the incidence of adverse reactions.
To investigate the analgesic mechanism of the active constituents of Piper wallichii.
The core targets related to analgesia of Piper wallichii were screened by network pharmacology, and GO functional enrichment and KEGG pathway enrichment analyses were carried out by DAVID database. The cationic elution site of Shinan vine was eluted by a silica gel column with a gradient(95:5-50:50)of petroleum ether-ethyl acetate separation system system to isolate the wallwort alkaloids, and the purity was determined by HPLC. Selected ICR mice were randomly divided into a blank group, positive control(aspirin 120 mg·kg-1)group, a model group, and low, medium, and high dose(150, 300, and 600 mg·kg-1)pellitorine groups(all n=8), and were administered continuously for 7 d. After the last administration, each group was injected intraperitoneally with 0.1 mL of 0.7% acetic acid for every 10 g of body weight except the blank group. The number of twisting responses and latency period in each group were examined. Serum levels of tumour necrosis factor(TNF)-α, interleukin(IL)-6 and IL-1β were detected by ELISA, and the concentrations of choline acetyltransferase(ChAT), acetylcholine(ACh), and acetylcholinesterase(AChE)were examined in brain tissues.
The network pharmacological results showed that Piper wallichii screened out the core components such as pellitorine and futoamide, and the key pathways such as nerve signalling pathway and cholinergic synaptic pathway. The purity of isolated pellitorine was 90.42%. Animal experiments showed that, compared with the model group, the number of twisting in the low, medium and high dose pellitorine groups was significantly reduced(P<0.05), and the content of TNF-α,IL-6 and IL-1β in serum was significantly reduced(P<0.01). ChAT in the brain tissues of the three dose pellitorine groups were significantly higher(P<0.01), and the concentration of ACh in the medium and high dose pellitorine groups were significantly higher(P<0.01), and the AChE concentration of low, middle and high dose pellitorine groups were significantly decreased(P<0.05).
The key active constituent in the analgesic effect of Piper wallichii is pellitorine, which is involved in the cholinergic synaptic pathway by up-regulating the activities of ChAT and ACh, and down-regulating AChE,thus reducing pain.