mRNA therapy is an emerging treatment that has become a frontier and hot topic in the field of biomedicine.To explore the trend in the development of mRNA therapy,this paper conducts an analysis from the perspectives of papers and patents,examining multiple dimensions including development trend,research areas,and high-value research.The study reveals the following findings:Global research in mRNA therapy is growing rapidly.Basic research mainly focuses on oncology,chemistry-multidisciplinary,biochemistry and molecular biology,while applied research centers on mRNA concerning genetic engineering,isolation,synthesis,purification,and the development of medicines.High-value research mainly centers on topics such as mRNA delivery,composition,manufacture,modification,and the development of various mRNA-based therapies.

Aim To explore the mechanism by which dioscin regulates IL-17+γδT cells in the treatment of arthritis.Methods A collagen-induced arthritis(CIA)model was established in DBA/1 mice using bovine type Ⅱ collagen.The mice were randomly divid-ed into the CIA model group,methotrexate(MTX)positive control group,and dioscin low-dose(Dioscin-L),medium-dose(Dioscin-M),and high-dose(Dios-cin-H)groups.After intervention,the therapeutic effects were evaluated using scoring methods.Joint pathological damage was analyzed by hematoxylin and eosin(HE)staining.The levels of anti-collagen-spe-cific antibodies and the pro-inflammatory cytokine IL-17 were measured by ELISA.The expressions of γδT cells and their subtypes,as well as the secretion level of IL-17,were detected by flow cytometry.Results Dioscin significantly reduced the arthritis severity score in collagen-induced arthritis(CIA)mice,alleviated joint pathological damage,inhibited the production of IL-17 by splenic lymphocytes and the levels of anti-col-lagen-specific antibodies total IgG and IgG3,and de-creased the proportion of γδT cells in the lymph nodes,splenic γδT cells,and the Vδ4+T-cell subset.The level of IL-17 produced by the Vδ4 subtype in the lymph nodes of the intervention groups was lower than that in the model group,but the difference was not sta-tistically significant.Conclusion Dioscin has signifi-cant therapeutic effect on CIA,and its mechanism may be through the inhibition of γδT cells,but it is unlikely to be related to IL-17 derived from γδT cells.

Aim To explore the mechanism by which dioscin regulates IL-17+γδT cells in the treatment of arthritis.Methods A collagen-induced arthritis(CIA)model was established in DBA/1 mice using bovine type Ⅱ collagen.The mice were randomly divid-ed into the CIA model group,methotrexate(MTX)positive control group,and dioscin low-dose(Dioscin-L),medium-dose(Dioscin-M),and high-dose(Dios-cin-H)groups.After intervention,the therapeutic effects were evaluated using scoring methods.Joint pathological damage was analyzed by hematoxylin and eosin(HE)staining.The levels of anti-collagen-spe-cific antibodies and the pro-inflammatory cytokine IL-17 were measured by ELISA.The expressions of γδT cells and their subtypes,as well as the secretion level of IL-17,were detected by flow cytometry.Results Dioscin significantly reduced the arthritis severity score in collagen-induced arthritis(CIA)mice,alleviated joint pathological damage,inhibited the production of IL-17 by splenic lymphocytes and the levels of anti-col-lagen-specific antibodies total IgG and IgG3,and de-creased the proportion of γδT cells in the lymph nodes,splenic γδT cells,and the Vδ4+T-cell subset.The level of IL-17 produced by the Vδ4 subtype in the lymph nodes of the intervention groups was lower than that in the model group,but the difference was not sta-tistically significant.Conclusion Dioscin has signifi-cant therapeutic effect on CIA,and its mechanism may be through the inhibition of γδT cells,but it is unlikely to be related to IL-17 derived from γδT cells.

mRNA therapy is an emerging treatment that has become a frontier and hot topic in the field of biomedicine.To explore the trend in the development of mRNA therapy,this paper conducts an analysis from the perspectives of papers and patents,examining multiple dimensions including development trend,research areas,and high-value research.The study reveals the following findings:Global research in mRNA therapy is growing rapidly.Basic research mainly focuses on oncology,chemistry-multidisciplinary,biochemistry and molecular biology,while applied research centers on mRNA concerning genetic engineering,isolation,synthesis,purification,and the development of medicines.High-value research mainly centers on topics such as mRNA delivery,composition,manufacture,modification,and the development of various mRNA-based therapies.

Objective The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area,namely,Qunlu Practice Base,Peach Blossom Garden,and Huangtong Animal Husbandry,and whether vectors carry any bacterial pathogens that may cause diseases to humans,to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit(OPU)analysis,we characterized the species-level microbial community structure of two important vector species,biting midges and ticks,including 33 arthropod samples comprising 3,885 individuals,collected around Poyang Lake. Results A total of 662 OPUs were classified in biting midges,including 195 known species and 373 potentially new species,and 618 OPUs were classified in ticks,including 217 known species and 326 potentially new species.Surprisingly,OPUs with potentially pathogenicity were detected in both arthropod vectors,with 66 known species of biting midges reported to carry potential pathogens,including Asaia lannensis and Rickettsia bellii,compared to 50 in ticks,such as Acinetobacter lwoffii and Staphylococcus sciuri.We found that Proteobacteria was the most dominant group in both midges and ticks.Furthermore,the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria.Pantoea sp7 was predominant in biting midges,while Coxiella sp1 was enriched in ticks.Meanwhile,Coxiella spp.,which may be essential for the survival of Haemaphysalis longicornis Neumann,were detected in all tick samples.The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion Biting midges and ticks carry large numbers of known and potentially novel bacteria,and carry a wide range of potentially pathogenic bacteria,which may pose a risk of infection to humans and animals.The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.

Objective:To explore the dosimetry difference between intensity-modulated radiotherapy (IMRT) and volumetric intensity modulated arc therapy (VMAT) based on the inner edge tangent field (IETF) after left-sided breast conserving surgery.Methods:The localization CT and target organ at risk (OAR) data of 35 patients with left-sided breast cancer treated with IMRT after breast conserving surgery at Department of Radiotherapy in Yunnan Cancer Hospital from June 2022 to June 2023 were selected. The IETF-IMRT and the IETF-VMAT plans were designed for the same patient based on IETF, the dosimetry differences of target areas and OAR, as well as the planned execution time were compared between the two groups.Results:Dosimetry of target areas: for IETF-IMRT and IETF-VMAT, the D 98% of the planning target volume were (47.92±0.51) and (48.21±0.33) Gy, respectively, while the D 50% were (52.04±0.22) and (51.91±0.26) Gy, respectively, and the D 2% were (53.93±0.36) and (53.62±0.41) Gy, respectively, the conformity index were 0.84±0.03 and 0.87±0.02, respectively, while the homogeneity index were 0.12±0.01 and 0.10±0.01, respectively, with statistically significant differences ( t=-3.87, P<0.001; t=3.53, P=0.001; t=5.30, P<0.001; t=-13.60, P<0.001; t=6.24, P<0.001). Dosimetry of OAR: for IETF-IMRT and IETF-VMAT, the left lung V 5 were (31.91±6.28) % and (33.99±6.31) %, respectively, and the V 20 were (11.71±2.06) % and (9.73±2.12) %, respectively, with statistically significant differences ( t=-4.18, P<0.001; t=12.40, P<0.001). The right lung V 5 were (0.11±0.08) % and (7.13±3.12) %, respectively, and the D mean were (1.05±0.12) and (2.71±0.27) Gy, respectively, with statistically significant differences ( t=-33.62, P<0.001; t=-13.30, P<0.001). The spinal cord D 2% were (1.08±0.11) and (4.83±1.40) Gy, respectively, with a statistically significant difference ( t=-15.99, P<0.001). The left lung D mean were (7.45±1.08) and (7.37±1.03) Gy, the heart D mean were (4.21±0.96) and (4.41±0.48) Gy, and the right-sided breast D mean were (3.74±1.52) and (3.48±1.11) Gy, respectively, with no statistically significant difference ( t=1.16, P=0.253; t=-1.76, P=0.088; t=1.41, P=0.169). Planned execution time: the execution time of IETF-IMRT and IETF-VMAT was (10.73±1.21) and (2.18±0.17) min, respectively, with a statistically significant difference ( t=44.71, P<0.001) . Conclusion:Both IETF-IMRT and IETF-VMAT can meet clinical requirements, however the two techniques have their own characteristics. IETF-VMAT has better conformity and homogeneity of target region. The planned OAR dosimetry in both plans are significantly lower than the dose limit of postoperative radiotherapy for breast cancer, among which the left lung V 5, the right lung V 5, D mean and spinal cord D 2% of IETF-IMRT are slightly lower, the left lung V 20 of IETF-VMAT is slightly lower. IETF-VMAT significantly reduces the planned execution time compared with IETF-IMRT, thus can greatly reduce the dose deviation caused by patient position change, and significantly improve patients experience and comfort of radiotherapy. Taken together, IETF-VMAT has advantages over IETF-IMRT in radiotherapy after breast conserving surgery of left-sided breast cancer.

Objective:To analyze the effects of different dose calculation grid size of Monaco system on the physical and biological dosimetry of target area and organ at risk (OAR) in T 4 nasopharyngeal carcinoma. Methods:A total of 18 patients with stage T 4 nasopharyngeal carcinoma who received radiotherapy in the Department of Radiotherapy of Yunnan Cancer Hospital from October 2020 to April 2022 were selected to complete the delineation of target areas and OAR in the Monaco 5.11.03 system, and the volumetric intensity modulated arc therapy (VMAT) plan was developed on the 3 mm grid with the optimization mode of target area priority. The 3 mm grid group plan was replicated without changing any other parameters, and the physical plan was re-established on the 1, 2, 4 and 5 mm grids, and then the five plans were normalized to the prescription dose to cover 95% of the target volume. The planning time, D 2%, D 50%, D 98%, conformity index (CI), homogeneity index (HI), gradient index (GI), tumor control probability (TCP), D 2% and D mean of important OAR around the target area were calculated and statistically analyzed. Results:Planning primary tumor gross target volume (PGTVp) : The D 2% of 1, 2, 3, 4 and 5 mm groups were (76.94±0.66), (75.98±0.76), (75.56±0.67), (75.67±0.73) and (75.94±0.85) Gy, respectively, with a statistically significant difference ( F=9.86, P<0.001). The CI of 1, 2, 3, 4 and 5 mm groups were 0.75±0.05, 0.78±0.04, 0.78±0.05, 0.79±0.04 and 0.78±0.04, respectively, with a statistically significant difference ( F=2.61, P=0.041). There were statistically significant differences in D 50%, D 98%, HI, equivalent uniform dose (EUD) and tumor control probability (TCP) among the groups ( H=17.14, P=0.002; F=9.35, P<0.001; H=25.43, P<0.001; F=5.85, P<0.001; H=17.65, P=0.001). There was no statistically significant difference in GI among the groups ( P>0.05). Pairwise comparison showed that D 2% in 2, 3, 4, 5 mm groups compared with 1 mm group, D 50% in 5 mm group compared with 2, 3 mm groups, D 98% in 4 mm group compared with 1, 2 mm groups, D 98% in 5 mm group compared with 1, 2, 3 mm groups, CI in 5 mm group compared with 1 mm group, HI in 2, 3, 4, 5 mm groups compared with 1 mm group, EUD in 3 mm group was compared with 1 mm group, EUD in 5 mm group compared with 2, 3 mm groups, TCP in 3 mm group compared with 1 mm group, and TCP in 5 mm group compared with 3 mm group, there were statistically significant differences (all P<0.05). Planning nodal gross target volume (PGTVn) : The D 2% of 1, 2, 3, 4 and 5 mm groups were (76.36±0.59), (75.36±0.62), (75.04±0.68), (75.25±0.72) and (75.39±0.77) Gy, respectively, with a statistically significant difference ( F=10.32, P<0.001). The HI of 1, 2, 3, 4 and 5 mm groups were 1.08 (1.08, 1.08), 1.07 (1.06, 1.07), 1.06 (1.06, 1.07), 1.06 (1.06, 1.07), 1.06 (1.06, 1.07), 1.06 (1.06, 1.08), respectively, with a statistically significant difference ( H=22.00, P<0.001) ; There were statistically significant differences in D 50%, D 98% and EUD among the groups ( H=11.79, P=0.019; H=20.49, P<0.001; F=12.14, P=0.016). Pairwise comparison showed that there were statistically significant differences in D 2% between 2, 3, 4, 5 mm groups and 1 mm group, D 98% between 4 mm group and 1 mm group, D 98% between 5 mm group and 1, 2 mm groups, HI between 2, 3, 4 mm groups and 1 mm group, and EUD between 3 mm group and 1 mm group (all P<0.05). Planning primary tumor clinical target volume 1 (PCTVp1) : The D 2% of 1, 2, 3, 4 and 5 mm groups were (76.59±0.63), (75.64±0.65), (75.64±0.98), (75.41±0.70) and (75.71±0.84) Gy, respectively, with a statistically significant difference ( F=9.53, P<0.001). The D 50% of 1, 2, 3, 4, 5 mm groups were (72.09±0.34), (71.85±0.39), (71.82±0.45), (72.04±0.56), (72.43±0.66) Gy, respectively, with a statistically significant difference ( F=4.20, P=0.019). There was no statistically significant difference in the other indexes among the groups (all P>0.05). Pairwise comparison showed that there were statistically significant differences in D 2% between 2, 3, 4, 5 mm groups and 1 mm group, and in D 50% between 2, 3 mm groups and 1 mm group (all P<0.05). Planning nodal clinical target volume 1 (PCTVn1) : There were no statistically significant differences in all indexes among the groups (all P>0.05). Planning clinical target volume 2 (PCTV2) : The D 2% of 1, 2, 3, 4 and 5 mm groups were (75.57±0.50), (74.87±0.67), (74.51±0.51), (74.61±0.63) and (75.00±0.74) Gy, respectively, with a statistically significant difference ( F=8.27, P<0.001). Pairwise comparison showed that the D 2% of the 2, 3, 4 mm groups were significantly different from that of the 1 mm group (all P<0.05). The calculation time of physical plan in 1, 2, 4 and 5 mm groups was 987.00 (848.00, 1 091.00), 120.50 (99.75, 134.00), 26.00 (24.00, 34.25) and 21.50 (18.75, 34.75) s, respectively, with a statistically significant difference ( H=61.62, P<0.001). Pairwise comparison showed that there were statistically significant differences in the calculation time between 4 mm group and 1, 2 mm groups, 5 mm group and 1, 2 mm groups (all P<0.05). There was no statistically significant difference in the dosimetric parameters of OAR around the target area among the groups (all P>0.05) . Conclusion:The physical dose and biological dose of the important OAR around the target area and the target area change with the change of dose calculation grid size when formulating the physical plan of radiotherapy for T 4 nasopharyngeal carcinoma. Considering the quality of the physical plan and the calculation time, when the Monaco system formulates the VMAT plan for T 4 nasopharyngeal carcinoma patients, the plan can be optimized on the 3 mm computing grid and copied to the 1 mm computing grid for recalculation.

OBJECTIVE: To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture (EA) in experimental models of Alzheimer's disease (AD) in vivo. METHODS: Senescence-accelerated mouse prone 8 (SAMP8) mice were used as AD models and received EA at Yingxiang (LI 20, bilateral) and Yintang (GV 29) points for 20 days. For certain experiments, SAMP8 mice were injected intravenously with human fibrin (2 mg). The Morris water maze test was used to assess cognitive and memory abilities. The changes of tight junctions of blood-brain barrier (BBB) in mice were observed by transmission electron microscope. The expressions of fibrin, amyloid- β (Aβ), and ionized calcium-binding adapter molecule 1 (IBa-1) in mouse hippocampus (CA1/CA3) were detected by reverse transcription-quantitative polymerase chain reaction (qRT-PCR), Western blot or immunohistochemical staining. The expression of fibrin in mouse plasma was detected by enzyme-linked immunosorbent assay. The expressions of tight junction proteins zonula occludens-1 and claudin-5 in hippocampus were detected by qRT-PCR and immunofluorescence staining. Apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. RESULTS: Fibrin was time-dependently deposited in the hippocampus of SAMP8 mice and this was inhibited by EA treatment (P<0.05 or P<0.01). Furthermore, EA treatment suppressed the accumulation of Aβ in the hippocampus of SAMP8 mice (P<0.01), which was reversed by fibrin injection (P<0.05 or P<0.01). EA improved SAMP8 mice cognitive impairment and BBB permeability (P<0.05 or P<0.01). Moreover, EA decreased reactive oxygen species levels and neuroinflammation in the hippocampus of SAMP8 mice, which was reversed by fibrin injection (P<0.05 or P<0.01). Mechanistically, EA inhibited the promoting effect of fibrin on the high mobility group box protein 1 (HMGB1)/toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE)/nicotinamide adenine dinucleotide phosphate (NADPH) signaling pathways (P<0.01). CONCLUSION EA may potentially improve cognitive impairment in AD via inhibition of fibrin/A β deposition and deactivation of the HMGB1/TLR4 and RAGE/NADPH signaling pathways.
Mice ; Humans ; Animals ; NADP/metabolism* ; Toll-Like Receptor 4 ; HMGB1 Protein/metabolism* ; Receptor for Advanced Glycation End Products/metabolism* ; Blood-Brain Barrier/metabolism* ; Neuroinflammatory Diseases ; Electroacupuncture ; Alzheimer Disease/therapy* ; Hippocampus/metabolism* ; Amyloid beta-Peptides/metabolism*