ArchiveChimeric 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.
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.
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.
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.
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.
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 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 evaluate the rationality of irinotecan application based on weighted TOPSIS method.
Based on the drug label of irinotecan, combined with relevant guidelines and literatures, weighted TOPSIS method was used to establish the evaluation criteria for the rationality of irinotecan clinical application, with “indications,contraindications, application and dosage, solvent selection, baseline examination, pretreatment, administration sequence,blood routine monitoring, dosage adjustment and ADR monitoring” as evaluation indicators. The archived medical records of inpatients who had used irinotecan in Binhu Hospital of Hefei from January 1, 2022 to May 31, 2023 were evaluated for the rationary of irinotecan administration.
Among the 10 evaluation indicators, the highest relative weighted index was indication(0.133 1), while the lowest was pretreatment(0.084 9). Among the included 97 cases, 10 cases(10%)had relative proximity(Ci)≥0.8, with the evaluation result as rational drug application; 79 cases(81%)had 0.6≤ Ci< 0.8,with the evaluation result as basic rational drug application; 8 cases(8%)had 0.4≤Ci < 0.6, with the evaluation result as irrational drug application.
The weighted TOPSIS method can be used to evaluate the rational usage of irinotecan. In our hospital, the use of irinotecan is basically reasonable, however, there are still some problems about baseline examination, blood routine monitoring and unreasonable indications.
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.
To explore the current research progress, research status, and future development directions in the field of traditional Chinese medicine(TCM)innovation.
CiteSpace software was used to analyze the paper trends and keywords in domestic journal articles between 1999 and 2023, and keyword clustering analysis, drawing timeline mapping,and emergent word analysis were used to visualize the field of Chinese medicine innovation in China.
The number of TCM innovation-related publications showed a fluctuating upward trend year by year. The research is still dominated by the researchers’ respective teams and lacks relevant team cooperation. The development of TCM research has entered a rapid development stage, which has envolved from the traditional research direction such as prescription research and development,it has developed to the construction of TCM data platform and intelligent production in the industry.
Research in the field of TCM innovation in China is developing steadily and undergoing a transformation towards diversification,digitization, and intelligence.
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.