In recent years, nucleic acid therapy, as a revolutionary therapeutic tool, has shown great potential in the treatment of genetic diseases, infectious diseases and cancer. Lipid nanoparticles (LNPs) are currently the most advanced mRNA delivery carriers, and their emergence is an important reason for the rapid approval and use of COVID-19 mRNA vaccines and the development of mRNA therapy. Currently, mRNA therapeutics using LNP as a carrier have been widely used in protein replacement therapy, vaccines and gene editing. Conventional LNP is composed of four components: ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG) lipids, which can effectively load mRNA to improve the stability of mRNA and promote the delivery of mRNA to the cytoplasm. However, in the face of the complexity and diversity of clinical diseases, the structure, properties and functions of existing LNPs are too homogeneous, and the lack of targeted delivery capability may result in the risk of off-targeting. LNPs are flexibly designed and structurally stable vectors, and the adjustment of the types or proportions of their components can give them additional functions without affecting the ability of LNPs to deliver mRNAs. For example, by replacing and optimizing the basic components of LNP, introducing a fifth component, and modifying its surface, LNP can be made to have more precise targeting ability to reduce the side effects caused by treatment, or be given additional functions to synergistically enhance the efficacy of mRNA therapy to respond to the clinical demand for nucleic acid therapy. It is also possible to further improve the efficiency of LNP delivery of mRNA through machine learning-assisted LNP iteration. This review can provide a reference method for the rational design of engineered lipid nanoparticles delivering mRNA to treat diseases.

Objective To describe the current state of research and future research hotspots through a metrological analysis of the literature in the field of forensic anthropological remains identification re-search.Methods The data retrieved and extracted from the Web of Science Core Collection (WoSCC),the core database of the Web of Science information service platform (hereinafter referred to as "WoS"),was used to analyze the trends and topic changes in research on forensic identification of human re-mains from 1991 to 2022.Network visualisation of publication trends,countries (regions),institutions,authors and topics related to the identification of remains in forensic anthropology was analysed using python 3.9.2 and Gephi 0.10.Results A total of 873 papers written in English in the field of forensic anthropological remains identification research were obtained.The journal with the largest number of publications was Forensic Science International (164 articles).The country (region) with the largest number of published papers was China (90 articles).Katholieke Univ Leuven (Netherlands,21 articles) was the institution with the largest number of publications.Topic analysis revealed that the focus of forensic anthropological remains identification research was sex estimation and age estimation,and the most commonly studied remains were teeth.Conclusion The volume of publications in the field of forensic anthropological remains identification research has a distinct phasing.However,the scope of both international and domestic collaborations remains limited.Traditionally,human remains identifica-tion has primarily relied on key areas such as the pelvis,skull,and teeth.Looking ahead,future re-search will likely focus on the more accurate and efficient identification of multiple skeletal remains through the use of machine learning and deep learning techniques.

Objective:To explore the effects of RNF113A on the proliferation,migration,in-vasion,apoptosis,and autophagy of hepatocellular carcinoma cells.Methods:Hep3B cells were divided into control group and RNF113A overexpression group(RNF113A-OE),HepG2 was divided into control group and RNF113A knockdown group(si-RNF113A),CCK-8 assay was used to detect changes in cell viability,clone formation assay was used to detect changes in cell proliferation abili-ty,Transwell assay was used to detect changes in cell invasion ability,wound healing assay was used to detect changes in cell migration ability,and flow cytometry was used to detect changes in cell apoptosis ability,Western blot experiments were used to detect changes in protein expression of autophagy related genes and AMPK signaling pathway related genes.Results:Compared with the control group,the proliferation,cloning,invasion,and migration abilities of Hep3B cells in the RNF113A-OE group were improved,while apoptosis and autophagy abilities were decreased,and the AMPK signaling pathway was inhibited;In the si-RNF113A group,the proliferation,cloning,in-vasion,and migration abilities of HepG2 cells were significantly reduced,while apoptosis and au-tophagy abilities were increased,and the activation of the AMPK signaling pathway was promoted.Conclusion:RNF113A promotes the proliferation,cloning,invasion,and migration of hepatocel-lular carcinoma cells,and inhibited apoptosis and autophagy by inhibiting the AMPK signaling path-way.

Objective:To investigate the effect of GRIM-19 on the resistance of carcinoma cells to the chemotherapeutic agent docetaxel in the treatment of PCa.Methods:Using siRNA technology to interfere with the gene expression in PCa cells,we estab-lished a model of GRIM-19 overexpression/knockdown in PCa cells.We investigated the effect of different expression levels of GRIM-19 on docetaxel-induced death of the PCa cells by qPCR,Western blot and flow cytometry,and assessed the value of GRIM-19 in re-ducing the chemotherapy-resistance of PCa cells.Results:GRIM-19 was down-regulated in PCa tissues and cells.Knockout of GRIM-19 significantly decreased the expression of siGRIM19 in the PC-3 and LNCaP cells,and reduced their death rate when treated with docetaxel compared with the control group.The expressions of GRIM-19 mRNA and protein were remarkably upregulated after transfection with GRIM-19,and the overexpressed GRIM-19 promoted the death of the PC-3 and LNCaP cells treated with docetaxel in a dose-dependent manner.Flow cytometry analysis showed a lower apoptosis rate of PC-3-R cells than that of PC-3 cells at different time points of docetaxel-induction at different doses.Conclusion:GRIM-19 is a PCa suppressor gene with a significant facilitating effect on the apoptosis of PCa cells,and the overexpression of GRIM-19 promotes docetaxel-induced PCa cell death and improves the sensitivity of chemotherapy.

OBJECTIVE: To observe the effect of preoperative, intraoperative and postoperative electroacupuncture (EA) intervention on postoperative urination function in patients with mixed hemorrhoid surgery. METHODS: A total of 240 patients with mixed hemorrhoid surgery under lumbar anesthesia were randomly divided into an EA preconditioning group (group A, 60 cases, 9 cases dropped off), an intraoperative EA group (group B, 60 cases, 4 cases dropped off), a postoperative EA group (group C, 60 cases, 6 cases dropped off), and a non-acupuncture group (group D, 60 cases, 3 cases dropped off). In the groups A, B and C, EA was exerted at Zhongliao (BL 33) and Huiyang (BL 35) , with disperse-dense wave, 4 Hz/20 Hz in frequency, and lasting 30 min, at 30 min before lumbar anesthesia, immediately after lumbar anesthesia and 6 h after surgery, respectively. No EA intervention was performed in the group D. The postoperative urination smoothness score in each group was observed 24 h after surgery. The first urination time, first urination volume, urine residual volume after first urination were recorded, and incidence of indwelling catheterization, postoperative visual analogue scale (VAS) score, number of remedial analgesia, and the incidence of postoperative nausea and vomiting were observed in each group. RESULTS: In the groups A, B and C, the postoperative urination smoothness scores were superior to the group D (P<0.05), and the time of first urination was earlier than the group D (P<0.05). In the group C, the time of first urination was earlier than the group A and the group B (P<0.05), the first urination volume was higher than the group D (P<0.05), and the urine residual volume after first urination was lower than the group D (P<0.05). There was no significant difference in the incidence of indwelling catheterization and postoperative nausea and vomiting among the 4 groups (P>0.05). The VAS scores of the group A, B and C were lower than that in the group D (P<0.05), and the number of remedial analgesia cases was lower than that in the group D (P<0.05). CONCLUSION EA intervention could promote the recovery of urination function and relieve postoperative pain in patients with mixed hemorrhoids surgery. Early postoperative EA intervention is more conducive to the recovery of urination function.
Humans ; Electroacupuncture ; Hemorrhoids/surgery* ; Urination ; Postoperative Nausea and Vomiting ; Acupuncture Points

Humans ; Mpox (monkeypox) ; China

This study investigated whether free prostate-specific antigen (fPSA) performs better than total PSA (tPSA) in predicting prostate volume (PV) in Chinese men with different PSA levels. A total of 5463 men with PSA levels of <10 ng ml^-1 and without prostate cancer diagnosis were included in this study. Patients were classified into four groups: PSA <2.5 ng ml^-1, 2.5-3.9 ng ml^-1, 4.0-9.9 ng ml^-1, and 2.5-9.9 ng ml^-1. Pearson/Spearman's correlation coefficient (r) and receiver operating characteristic (ROC) curves were used to evaluate the ability of tPSA and fPSA to predict PV. The correlation coefficient between tPSA and PV in the PSA <2.5 ng ml^-1 cohort (r = 0.422; P < 0.001) was markedly higher than those of the cohorts with PSA levels of 2.5-3.9 ng ml^-1, 4.0-9.9 ng ml^-1, and 2.5-9.9 ng ml^-1 (r = 0.114, 0.167, and 0.264, respectively; all P ≤ 0.001), while fPSA levels did not differ significantly among different PSA groups. Area under ROC curve (AUC) analyses revealed that the performance of fPSA in predicting PV ≥40 ml (AUC: 0.694, 0.714, and 0.727) was better than that of tPSA (AUC = 0.545, 0.561, and 0.611) in men with PSA levels of 2.5-3.9 ng ml^-1, 4.0-9.9 ng ml^-1, and 2.5-9.9 ng ml^-1, respectively, but not at PSA levels of <2.5 ng ml^-1 (AUC: 0.713 vs 0.720). These findings suggest that the relationship between tPSA and PV may vary with PSA level and that fPSA is more powerful at predicting PV only in the ''gray zone'' (PSA levels of 2.5-9.9 ng ml^-1), but its performance was similar to that of tPSA at PSA levels of <2.5 ng ml^-1.
Male ; Humans ; Prostate-Specific Antigen ; Prostate ; East Asian People ; Prostatic Neoplasms/diagnosis* ; ROC Curve

The extraordinary advantages associated with mRNA vaccines, including their high efficiency, relatively low severity of side effects, and ease of manufacture, have enabled them to be a promising immunotherapy approach against various infectious diseases and cancers. Nevertheless, most mRNA delivery carriers have many disadvantages, such as high toxicity, poor biocompatibility, and low efficiency in vivo, which have hindered the widespread use of mRNA vaccines. To further characterize and solve these problems and develop a new type of safe and efficient mRNA delivery carrier, a negatively charged SA@DOTAP-mRNA nanovaccine was prepared in this study by coating DOTAP-mRNA with the natural anionic polymer sodium alginate (SA). Intriguingly, the transfection efficiency of SA@DOTAP-mRNA was significantly higher than that of DOTAP-mRNA, which was not due to the increase in cellular uptake but was associated with changes in the endocytosis pathway and the strong lysosome escape ability of SA@DOTAP-mRNA. In addition, we found that SA significantly increased the expression of LUC-mRNA in mice and achieved certain spleen targeting. Finally, we confirmed that SA@DOTAP-mRNA had a stronger antigen-presenting ability in E. G7-OVA tumor-bearing mice, dramatically inducing the proliferation of OVA-specific CLTs and ameliorating the antitumor effect. Therefore, we firmly believe that the coating strategy applied to cationic liposome/mRNA complexes is of potential research value in the field of mRNA delivery and has promising clinical application prospects.

As arsenic widely exists in nature and has been used in the pharmaceutical preparations, the traditional Chinese medicine(TCM) with arsenic include realgar(As_2S_2 or As_4S_4), orpiment(As_2S_3), and white arsenic(As_2O_3). Among the above representative medicine, the TCM compound formulas with realgar are utilized extensively. Just in Chinese Pharmacopoeia(2020 edition), there are 37 Chinese patent medicines including realgar. The traditional element analysis focuses on the detection of the total amount of elements, which neglects the study on the speciation and valence of elements. The activity, toxicity, bioavailability, and metabolic pathways of arsenic in vivo are closely related to the existence of its form, and different forms of arsenic have different effects on organisms. Therefore, the study on the speciation and valence of arsenic is of great importance for arsenic-containing TCMs and their compound formulas. This paper reviewed four aspects of the speciation and valence of arsenic, including property, absorption and metabolism, toxicity, and analytical assay.
Arsenic/analysis* ; Arsenicals/analysis* ; Sulfides ; Arsenic Trioxide ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/analysis* ; Biological Products

Fermented Chinese medicine has long been used. Amid the advance for preservation of experience, the connotation of fermented Chinese medicine has been enriched and improved. However, fermented Chinese medicine prescriptions generally contain a lot of medicinals. The fermentation process is complicated and the conventional fermentation conditions fail to be strictly controlled. In addition, the judgment of the fermentation end point is highly subjective. As a result, quality of fermented Chinese medicine is of great difference among regions and unstable. At the moment, the quality standards of fermented Chinese medicine are generally outdated and different among regions, with simple quality control methods and lacking objective safe fermentation-specific evaluation indictors. It is difficult to comprehensively evaluate and control the quality of fermented medicine. These problems have aroused concern in the industry and also affected the clinical application of fermented Chinese medicine. This article summarized and analyzed the application, quality standards, and the modernization of fermentation technology and quality control methods of fermented Chinese medicine and proposed suggestions for improving the quality standards of the medicine, with a view to improving the overall quality of it.
Medicine, Chinese Traditional ; Reference Standards ; Quality Control ; Fermentation