RNA-based gene therapy has been widely used for various diseases, and extensive studies have proved that suitable delivery routes greatly help the development of RNA therapeutics. Identifying a safe and effective delivery system is key to realizing RNA therapeutics' clinical translation. Inhalation is a non-invasive pulmonary delivery modality that can enhance the retention of therapeutic agents in the lungs with negligible toxicity, thereby improving patient compliance. Inhaled RNA therapeutics are increasingly becoming an area of focus for researchers; however, only several clinical trials have explored inhaled delivery of RNA for pulmonary diseases. This review presents an overview of recent advances in inhaled delivery systems for RNA therapeutics, including viral and nonviral systems, highlighting state of the art regarding inhalation in the messenger RNA (mRNA) field. We also summarize the applications of mRNA inhalants in infectious and other lung diseases. Simultaneously, the research progresses on small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs), and different types of RNA are also discussed to provide new strategies for developing RNA inhalation therapy. Finally, we clarify the challenges inhaled RNA-based therapeutics face before their widespread adoption and provide insights to help advance this exciting field to the bedside.

Objective To analyze the current status of clinical trial registration in the TCM treatment of diabetic nephropathy(DN);To provide references for the registration and implementation of relevant clinical trials.Methods Clinical trials about TCM treatment for DN registered in the Chinese Clinical Trial Registry(ChiCTR)and the U.S.Clinical Trial Registry(ClinicalTrials.gov)from their inception to August 18,2024 were retrieved.The following information was analyzed:registration year,geographical distribution,funding sources,TCM syndrome patterns of participants,number of research centers,sample size,study type,study design,randomization method,blinding method,intervention measures,outcome indicators and safety indicators.Results A total of 88 clinical trials were included,comprising 79 interventional studies and 9 observational studies.The number of registrations has increased annually.The domestic registered trials were distributed across 17 provincial-level administrative regions in China,with Beijing and Shanghai having the highest number of registrations.The primary sources of funding were local and national government funds.The most common TCM syndrome pattern among participants was qi-yin deficiency with blood stasis.Most trials were single-center studies,with the majority having a sample size between 31 and 60.The predominant study type was interventional,mostly randomized controlled trials(RCTs),with simple randomization being the most frequently used method.31 trials reported blinding methods,with double-blinding being the most common.The intervention measures were mostly oral Chinese patent medicines or TCM compounds,and the outcome indicators were mainly efficacy indicators,with less safety indicators.Conclusion The number of registered clinical trials on TCM treatment for DN has increased annually;however,the overall number remains limited.There is uneven regional distribution and incomplete registration information for various factors such as randomization methods,blinding methods,number of research centers,intervention measures,and outcome indicators.

Anti-tumor drug research and development in non-small cell lung cancer (NSCLC) is rapidly developing, and the clinical application of high-throughput sequencing technology is also becoming widespread. Accordingly, researchers are focusing on human epidermal growth factor receptor-2 (HER-2) gene as a rare target of NSCLC, and a series of exploratory studies has been performed. Traditional chemotherapy and immunotherapy are unsatisfactory in the HER-2 mutant population, whereas the survival improvement of anti-HER-2 monoclonal antibodies and pan-HER inhibitors is limited. The development of antibody drug conjugate (ADC) ushers in a turning point for HER-2-mutated NSCLC, and new ADC drugs represented by trastuzumab deruxtecan are making a breakthrough. It opens up a new era of precision therapy for advanced HER-2-mutated NSCLC. Additionally, novel HER-2 inhibitors show very encouraging initial efficacy and safety, and clinical trials are ongoing. This review focuses on the latest progress of research on HER-2-mutated NSCLC.

OBJECTIVE: To observe the efficacy and safety of Tiaowei Jiannao acupuncture (acupuncture for regulating defensive qi and nourishing brain) for post-ischemic stroke insomnia (PISI). METHODS: A total of 96 patients with PISI were randomized into an acupuncture group (32 cases, 1 case was excluded), a medication group (32 cases, 1 case dropped out, 1 case was excluded) and a sham-acupuncture group (32 cases, 1 case dropped out, 1 case was excluded). In the acupuncture group, Tiaowei Jiannao acupuncture was applied at bilateral Shenmai (BL62), Zhaohai (KI6), Hegu (LI4), Taichong (LR3), and Baihui (GV20), Sishencong (EX-HN1), Yintang (GV24⁺), Shenting (GV24), once a day, 1-day interval was taken after 6-day treatment, for 3 weeks totally. In the medication group, eszopiclone tablet was given orally, 1-3 mg a time, once a day for 3 weeks. In the sham-acupuncture group, non-invasive sham acupuncture was applied, the acupoint selection, frequency and course of treatment were the same as the acupuncture group. Before treatment, after 2,3 weeks of treatment, the scores of Pittsburgh sleep quality index (PSQI), self-rating sleep scale (SRSS), National Institutes of Health Stroke scale (NIHSS), Hamilton depression scale-17 (HAMD-17) were observed; before and after treatment, the sleep parameters were recorded using polysomnography (PSG); and the efficacy and safety were evaluated after treatment in the 3 groups. RESULTS: After 2,3 weeks of treatment, the scores of PSQI, HAMD-17 and SRSS in the acupuncture group and the medication group, as well as the SRSS scores in the sham-acupuncture group were decreased compared with those before treatment (P<0.05); after 2 weeks of treatment, the NIHSS score in the acupuncture group was decreased compared with that before treatment (P<0.05); after 3 weeks of treatment, the NIHSS scores in the acupuncture group, the medication group and the sham-acupuncture group were decreased compared with those before treatment (P<0.05). After 3 weeks of treatment, the scores of PSQI, SRSS, HAMD-17 and NIHSS in the acupuncture group and the medication group, as well as the NIHSS score in the sham-acupuncture group were decreased compared with those after 2 weeks of treatment (P<0.05). After 2,3 weeks of treatment, the scores of PSQI, SRSS and HAMD-17 in the acupuncture group and the medication group were lower than those in the sham-acupuncture group (P<0.05), the NIHSS scores in the acupuncture group were lower than those in the medication group and the sham-acupuncture group (P<0.05); after 3 weeks of treatment, HAMD-17 score in the acupuncture group was lower than that in the medication group (P<0.05), the NIHSS score in the medication group was lower than that in the sham-acupuncture group (P<0.05). Compared before treatment, after treatment, the total sleep time was prolonged (P<0.05), the wake after sleep onset, sleep latency, and non-rapid eye movement (NREM) sleep latency were shortened (P<0.05), the sleep efficiency was improved (P<0.05), the number of awakenings was reduced (P<0.05), the percentage of rapid eye movement (REM%) and the percentage of NREM stage 1 (N1%) were decreased (P<0.05), the percentage of NREM stage 2 (N2%) and the percentage of NREM stage 3 (N3%) were increased (P<0.05) in the acupuncture group and the medication group; the sleep latency was shortened in the sham-acupuncture group (P<0.05). After treatment, the PSG indexes in the acupuncture group and the medication group were superior to those in the sham-acupuncture group (P<0.05); in the acupuncture group, the number of awakenings was less than that in the medication group (P<0.05), the REM% and N1% were lower than those in the medication group (P<0.05), the N2% and N3% were higher than those in the medication group (P<0.05). The total effective rate were 93.5% (29/31) and 90.0% (27/30) in the acupuncture group and the medication group respectively, which were higher than 10.0% (3/30) in the sham-acupuncture group (P<0.05). There was no serious adverse events in any of the 3 groups. CONCLUSION Tiaowei Jiannao acupuncture improves the insomnia symptoms in patients with ischemic stroke, improves the quality of sleep, increases the deep sleep, promotes the recovery of neurological function, and relieves the depression. It is effective and safe for the treatment of PISI.
Humans ; Acupuncture Therapy ; Male ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Female ; Middle Aged ; Aged ; Acupuncture Points ; Treatment Outcome ; Adult ; Ischemic Stroke/complications* ; Stroke/complications* ; Sleep

BACKGROUND:Knee osteoarthritis is a common degenerative disease that significantly impacts patients'quality of life and increases the societal healthcare burden.Early and accurate diagnosis of knee osteoarthritis is crucial for the treatment and prognosis of patients.Traditional diagnostic methods are not only subjective and time-consuming but also do not guarantee consistently high accuracy.OBJECTIVE:To develop an automatic diagnostic method for knee osteoarthritis based on deep learning,utilizing deep learning networks to improve diagnostic accuracy and efficiency.METHODS:A new network model,YOLOV8-ViT,was proposed by replacing the backbone network of YOLOv8n with the Efficient-ViT network and incorporating attention mechanisms for the automatic identification and classification of X-ray images of knee osteoarthritis.The experimental dataset included 5 078 X-ray images of patients with knee osteoarthritis obtained from the Third Affiliated Hospital of Guangzhou University of Chinese Medicine.Three imaging physicians annotated the sites of knee osteoarthritis and classified them according to the Kellgren-Lawrence grading standard using Labelme software,and the results were combined.The evaluation indicators used in this study included Precision,F1 score,mean average precision(mAP),Recall,val/box_loss,val/cls_loss,and val/dfl_loss.RESULTS AND CONCLUSION:The experimental results showed that the YOLOV8-ViT model outperformed the YOLOv5n,YOLOv8n,and YOLOv9n models in terms of precision,mAP50,mAP50-95,F1 score,and Recall,while lowering val/box_loss,val/cls_loss,and val/dfl_loss by 0.496,0.45,and 0.523;1.037,0.305,and 0.728;and 0.267,0.654,and 0.854,respectively.These experimental data validate that this model has high detection accuracy.

Objective To investigate the prognostic value of thrombin-antithrombin III complex(TAT),plasmin-α2-plasmin inhibitor complex(PIC),thrombomodulin(TM)and tissue plasminogen activator-inhibitor complex(t-PAIC)in patients with myelodysplastic syndrome(MDS).Methods Selected 88 primary MDS patients diagnosed at the 521 Hospital of Ordnance Industry from January 2018 to January 2021.Plasma levels of TAT,PIC,TM,t-PAIC,fibrin degradation products(FDP)and D-dimer(D-D)were measured.A multivariate approach was used to analyze the association between overall survival(OS)and the levels of each coagulation marker.Coagulation markers significantly associated with OS were used to construct a coagulation prognostic scoring system.Based on the median coagulation marker score,MDS patients were divided into high and low score groups.Kaplan-Meier analysis was used to plot survival curves.Results TAT(OR=1.667),PIC(OR=0.734),TM(OR=1.294)and t-PAIC(OR=1.523)were independent factors influencing OS in MDS patients(Wald χ2=0.671～10.751,all P<0.05).The β-values were integrated as statistical weights to construct a coagulation marker score,calculated as follows:[TAT]×0.502-[PIC]×1.013+[TM]×0.181+[t-PAIC]×0.381.The OS(median 14.6 months)and leukemia free survival(LFS)(median 10.3 months)of patients in the high coagulation marker score group were significantly lower than those in the low score group(33.6 months,35.2 months)(Log rank=20.57,26.84,all P<0.001).Subgroup analysis indicated that in both the low-risk IPSS-R subgroup(very low,low,and intermediate risk)and the high-risk IPSS-R subgroup(high and very high risk),the OS(Log rank=9.12,4.30)and LFS(Log rank=4.54,8.51)of the high coagulation marker score group were lower than those of the low score group(all P<0.05).Bivariate analysis showed a moderate correlation between the coagulation marker score and Revise International Prognostic Scoring System(IPSS-R)(PCC=0.536,P<0.001).Multivariate analysis indicated that IPSS-R and high coagulation marker scores were independent risk factors for OS and LFS in MDS patients(P<0.05).Conclusion The coagulation marker score,based on TAT,PIC,TM and t-PAIC,can serve as an independent prognostic factor for OS and LFS in MDS patients.

Objective To investigate the prognostic value of thrombin-antithrombin III complex(TAT),plasmin-α2-plasmin inhibitor complex(PIC),thrombomodulin(TM)and tissue plasminogen activator-inhibitor complex(t-PAIC)in patients with myelodysplastic syndrome(MDS).Methods Selected 88 primary MDS patients diagnosed at the 521 Hospital of Ordnance Industry from January 2018 to January 2021.Plasma levels of TAT,PIC,TM,t-PAIC,fibrin degradation products(FDP)and D-dimer(D-D)were measured.A multivariate approach was used to analyze the association between overall survival(OS)and the levels of each coagulation marker.Coagulation markers significantly associated with OS were used to construct a coagulation prognostic scoring system.Based on the median coagulation marker score,MDS patients were divided into high and low score groups.Kaplan-Meier analysis was used to plot survival curves.Results TAT(OR=1.667),PIC(OR=0.734),TM(OR=1.294)and t-PAIC(OR=1.523)were independent factors influencing OS in MDS patients(Wald χ2=0.671～10.751,all P<0.05).The β-values were integrated as statistical weights to construct a coagulation marker score,calculated as follows:[TAT]×0.502-[PIC]×1.013+[TM]×0.181+[t-PAIC]×0.381.The OS(median 14.6 months)and leukemia free survival(LFS)(median 10.3 months)of patients in the high coagulation marker score group were significantly lower than those in the low score group(33.6 months,35.2 months)(Log rank=20.57,26.84,all P<0.001).Subgroup analysis indicated that in both the low-risk IPSS-R subgroup(very low,low,and intermediate risk)and the high-risk IPSS-R subgroup(high and very high risk),the OS(Log rank=9.12,4.30)and LFS(Log rank=4.54,8.51)of the high coagulation marker score group were lower than those of the low score group(all P<0.05).Bivariate analysis showed a moderate correlation between the coagulation marker score and Revise International Prognostic Scoring System(IPSS-R)(PCC=0.536,P<0.001).Multivariate analysis indicated that IPSS-R and high coagulation marker scores were independent risk factors for OS and LFS in MDS patients(P<0.05).Conclusion The coagulation marker score,based on TAT,PIC,TM and t-PAIC,can serve as an independent prognostic factor for OS and LFS in MDS patients.

Objective To analyze the current status of clinical trial registration in the TCM treatment of diabetic nephropathy(DN);To provide references for the registration and implementation of relevant clinical trials.Methods Clinical trials about TCM treatment for DN registered in the Chinese Clinical Trial Registry(ChiCTR)and the U.S.Clinical Trial Registry(ClinicalTrials.gov)from their inception to August 18,2024 were retrieved.The following information was analyzed:registration year,geographical distribution,funding sources,TCM syndrome patterns of participants,number of research centers,sample size,study type,study design,randomization method,blinding method,intervention measures,outcome indicators and safety indicators.Results A total of 88 clinical trials were included,comprising 79 interventional studies and 9 observational studies.The number of registrations has increased annually.The domestic registered trials were distributed across 17 provincial-level administrative regions in China,with Beijing and Shanghai having the highest number of registrations.The primary sources of funding were local and national government funds.The most common TCM syndrome pattern among participants was qi-yin deficiency with blood stasis.Most trials were single-center studies,with the majority having a sample size between 31 and 60.The predominant study type was interventional,mostly randomized controlled trials(RCTs),with simple randomization being the most frequently used method.31 trials reported blinding methods,with double-blinding being the most common.The intervention measures were mostly oral Chinese patent medicines or TCM compounds,and the outcome indicators were mainly efficacy indicators,with less safety indicators.Conclusion The number of registered clinical trials on TCM treatment for DN has increased annually;however,the overall number remains limited.There is uneven regional distribution and incomplete registration information for various factors such as randomization methods,blinding methods,number of research centers,intervention measures,and outcome indicators.

BACKGROUND:Knee osteoarthritis is a common degenerative disease that significantly impacts patients'quality of life and increases the societal healthcare burden.Early and accurate diagnosis of knee osteoarthritis is crucial for the treatment and prognosis of patients.Traditional diagnostic methods are not only subjective and time-consuming but also do not guarantee consistently high accuracy.OBJECTIVE:To develop an automatic diagnostic method for knee osteoarthritis based on deep learning,utilizing deep learning networks to improve diagnostic accuracy and efficiency.METHODS:A new network model,YOLOV8-ViT,was proposed by replacing the backbone network of YOLOv8n with the Efficient-ViT network and incorporating attention mechanisms for the automatic identification and classification of X-ray images of knee osteoarthritis.The experimental dataset included 5 078 X-ray images of patients with knee osteoarthritis obtained from the Third Affiliated Hospital of Guangzhou University of Chinese Medicine.Three imaging physicians annotated the sites of knee osteoarthritis and classified them according to the Kellgren-Lawrence grading standard using Labelme software,and the results were combined.The evaluation indicators used in this study included Precision,F1 score,mean average precision(mAP),Recall,val/box_loss,val/cls_loss,and val/dfl_loss.RESULTS AND CONCLUSION:The experimental results showed that the YOLOV8-ViT model outperformed the YOLOv5n,YOLOv8n,and YOLOv9n models in terms of precision,mAP50,mAP50-95,F1 score,and Recall,while lowering val/box_loss,val/cls_loss,and val/dfl_loss by 0.496,0.45,and 0.523;1.037,0.305,and 0.728;and 0.267,0.654,and 0.854,respectively.These experimental data validate that this model has high detection accuracy.

Rosuvastatin(RVS)is an excellent drug with anti-inflammatory and lipid-lowering properties in the aca-demic and medical fields.However,this drug faces a series of challenges when used to treat atherosclerosis caused by hyperhomocysteinemia(HHcy),including high oral dosage,poor targeting,and long-term toxic side effects.In this study,we applied nanotechnology to construct a biomimetic nano-delivery system,macrophage membrane(M?m)-coated RVS-loaded Prussian blue(PB)nanoparticles(MPR NPs),for improving the bioavailability and targeting capacity of RVS,specifically to the plaque lesions associated with HHcy-induced atherosclerosis.In vitro assays demonstrated that MPR NPs effectively inhibited the Toll-like receptor 4(TLR4)/hypoxia-inducible factor-1α(HIF-1α)/nucleotide-binding and oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathways,reducing pyroptosis and inflammatory response in macrophages.Additionally,MPR NPs reversed the abnormal distribution of adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1)/ATP binding cassette transporter G1(ABCA1)/ATP binding cassette transporter G1(ABCG1)caused by HIF-1α,promoting cholesterol efflux and reducing lipid deposition.In vivo studies using apolipoprotein E knockout(ApoE-/-)mice confirmed the strong efficacy of MPR NPs in treating atherosclerosis with favorable bio-security,and the mechanism behind this efficacy is believed to involve the regulation of serum metabolism and the remodeling of gut microbes.These findings suggest that the synthesis of MPR NPs provides a promising nanosystem for the targeted therapy of HHcy-induced atherosclerosis.