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 investigate the predictive value of combined plasma gluconic acid(GA),fumaric acid(FA),and pseudouridine levels at admission for acute kidney injury(AKI)in elderly patients with acute myocardial infarction(AMI).Methods A total of 78 elderly AMI patients transferred from Emergency Department to Coronary Care Unit in Fuwai Hospital during Decem-ber 2021 and July 2022 were enrolled in this prospective study.They were divided into AKI group(40 cases)and non-AKI group(38 cases)according to whether they developed AKI during hospi-talization.Plasma levels of GA,FA and pseudouridine were quantitatively detected with liquid chromatography-tandem mass spectrometry.ROC curve was plotted to assess the predictive value of these three plasma metabolites for AKI in AMI patients.Multivariate logistic regression analy-sis was applied to analyze the clinical risk factors for AKI.Results There were no statistical differences in the plasma levels of GA,FA and pseudouridine between the AKI group and the non-AKI group(P＞0.05).ROC curve analysis revealed that the plasma levels of the three indicators had no predictive value for the development of AKI in elderly AMI patients(AUC=0.576,95％CI:0.449-0.704,P=0.246;AUC=0.595,95％CI:0.467--0.721,P=0.154;AUC=0.563,95％CI:0.435-0.692,P=0.337).Multivariate logistic regression analysis revealed that left ventricu-lar ejection fraction(LVEF)was an independent predictor for AKI development in elderly AMI patients(OR=0.923,95％CI:0.870-0.978,P=0.007).Conclusion Plasma GA,FA and pseud-ouridine cannot predict the development of AKI in elderly AMI patients,while,LVEF is an inde-pendent predictor for the development.

Objective:To explore the repair methods and effects of refractory wounds in patients after spinal internal fixation operation .Methods:The study was a retrospective observational study. From November 2020 to October 2023, 10 patients with refractory wounds after spinal internal fixation operation were admitted to the Department of Burns and Plastic Surgery of Changde Hospital of Xiangya School of Medicine of Central South University. They were 3 males and 7 females, aged 35 to 68 years. There were 6 cases of thoracolumbar tuberculosis, 3 cases of thoracolumbar fracture, and 1 case of recurrent sacrococcygeal chordoma with skin, soft tissue, and bone defects after radical resection. The wound areas after debridement were 6.0 cm×1.5 cm to 27.0 cm×6.5 cm. The wound repair operation was decided to perform in the primary stage or in the secondary stage according to the wound situation. Two patients with type Ⅰ wounds were treated with debridement, direct suture, and continuous irrigation and drainage with catheter after operation. Eight patients with type Ⅱ wounds were repaired with local flaps (including rotation flap with dermis-fat flap at the end), muscle flaps, or muscle flaps combined with local flaps. The flap sizes were 10.0 cm×5.0 cm to 27.0 cm×14.0 cm, and the sizes of muscle flap were 8.0 cm×5.0 cm×4.0 cm to 17.0 cm×9.5 cm×2.0 cm. The wounds in flap donor areas were sutured directly. The wound treatment methods of patients with type Ⅱ wounds were recorded. The wound healing was observed after operation. The infection and recurrence of wounds, the retention of internal fixation materials, and spinal motor function were observed during follow-up.Results:Among patients with type Ⅱ wounds, there were 3 cases applied with local flaps (including 1 case with rotation flap with dermis-fat flap at the end), 3 cases with muscle flaps (including 1 case with latissimus dorsi muscle flap and 2 cases with erector spinal muscle flaps), and 2 cases with muscle flaps (1 case with latissimus dorsi muscle flap and 1 case with erector spinal muscle flap) combined with local flaps. Only 1 case with secondary defects after radical surgery of sacrococcygeal chordoma had poor wound healing which healed after dressing change, and the wounds of the remaining 9 cases all healed well. During the follow-up of 4 to 18 months, no infection or recurrence of local wounds developed in 10 patients, the internal fixation materials were not loosening, and there was no significant limitation in spinal motor function.Conclusions:For refractory wounds after spinal internal fixation operation, according to the wound type of patients, debridement, suture, irrigation, and drainage in the primary stage, or transplantation of local flaps, muscle flaps, muscle flaps combined with local flaps are performed in the primary stage or in the secondary stage. These methods are proved to have reliable therapeutic effects, not only repairing the wounds, but also retaining the internal fixation materials.

Objective The study aimed to construct and validate a predictive model for pulmonary nodules(PN)nature based on clinicopa-thological features,imaging,and serum biomarkers,so as to provide scientificdecision-making for early diagnosis and treatment of lung cancer.Methods A retrospective was performed on 816 PN patients with definited pathological diagnosis who received surgical resection analysisor lung biopsy in the Department of Thoracic Surgery and Oncology of Shenzhen Traditional Chinese Medicine Hospital from January 2019 to February 2023.Among them,113 cases that did not meet the inclusion criteria were excluded,and the remaining 703 cases were included in the study.The study based on the clinicopathologic features(age,gender,smoking history,smoking cessation history and family history of cancer),chest imaging(maximum diameter of nodule,location of lesion,clear border,Lobulation,spiculation,vascular convergence sign,vacuole,calcification,air bronchial sign,emphysema,nodule type and pleural indentation,nodule number)and serum carcinoembryonic antigen(CEA),cytokeratin 19 fragment(CYFRA21-1),squamous cell carcinoma antigen(SCCA)in patients with PN.These cases were randomly divided into a modeling group(n=552,237 benign,315 malignant)and a validation group(n=151,85 benign,66 malignant).First,univariate analysis was performed to screen for statistically significant predictors of nodules nature.Then,multivariate regression analysis was performed to screen for independent predictors of nodules nature.Finally,the prediction model of PN nature was constructed by logistic regression analysis.Subsequently,the validation group data were entered into the proposed model and Mayo clinic(Mayo)model,veterans affairs(VA)model,Brock University(Brock)model,Peking University(PKU)model and Guangzhou Medical University(GZMU)model,respectively.PN malignancy probability was calculated.The receiver operating characteristic(ROC)curves were plotted.The diagnostic efficiency of each model was compared according to the area under the curve(AUC).Results There were statistically significant variables including age,family history of cancer,maximum nodule diameter,nodule type,upper lobe of lung,calcification,vascular convergence sign,lobulation,clear border,spiculation,and serum CEA,SCCA,CYFRA21-1 using univariate analysis.Multiple regression analysis showed that age,CEA,clear border,CYFRA21-1,SCCA,upper lobe of lung,maximum nodule diameter,family history of cancer,spiculation and nodule type were independent predictors of PN nature.The prediction model equation constructed in this study is as follows:f(x)= ex/(1+ex),X=(-6.318 8+0.020 8×Age+0.527 4×CEA-0.928 4×clear border+0.294 6×Cyfra21-1+0.294×maximum nodule diameter+1.220 1×family history of cancer +0.573 2×upper lobe of lung +0.064 8×SCCA +1.461 5×Spiculation +1.497 6×nodule type).The AUC(0.799 vs 0.659,0.650)of the proposed model was significantly higher compared with Mayo model and VA model,and there were statistically significant differences(Z=3.029,2.638,P=0.003,0.008).However,compared with Brock model,PKU model and GZMU model,the differences of AUC(0.799 vs 0.762,0.773,0.769)were not statistically significant(Z=1.063,0.686,0.757,P=0.288,0.493,0.449).Conclusion The prediction model for PN nature established in this study is accurate and reliable,which can help clinics with early diagnosis and early intervention,and this prediction model deserves to be popularized.

Objective:To explore the strategy of how to select an effective flap for reconstruction of the surgical defect in clavicular region after resection of malignant tumour and care for the aesthetic appearance of the flap donor site.Methods:A retrospective observational study was conducted. Twenty-three patients with soft tissue malignant tumour in clavicle region were treated, from March 2017 to April 2023, in the Department of Burn and Plastic Surgery of Changde Hospital, Xiangya School of Medicine, Central South University (the First People’s Hospital of Changde). The patients were 13 males and 10 females, aged 21 to 72 years old. Ten patients were of dermatofibrosarcoma protuberans, 6 of fibrosarcoma, 3 of squamous cell carcinoma of skin, 3 of undifferentiated pleomorphic sarcoma and 1 of mucinous adenocarcinoma. Nine patients had the first surgery and 14 were with tumour recurrence and had previousely received one or more surgery in other hospitals. The tumour size ranged from 2.0 cm×4.5 cm×1.0 cm to 10.0 cm×16.0 cm×3.0 cm. After radical resection, the sizes of surgical defect ranged from 9.0 cm×12.0 cm to 16.0 cm×22.0 cm. All the clavicular soft tissue malignancies had radical resection, and the secondary surgical defects were further modified to reduce the short and long dimensions of the defects. Flaps were selected according to the short dimension, depth and skin elasticity of the flap donor site. Of the 23 patients, 3 were treated with free inguinal flaps, 9 with ipsilateral pedicled latissimus dorsi flaps or thoracodorsal artery perforator flaps, 5 with free deep inferior epigastric artery perforator flap (DIEPF), 5 with free anterolateral thigh flap (ALTF) and 1 with free rectus abdominis flap. The modified defects sized 5.0 cm × 11.0 cm-12.0 cm×19.0 cm after the suture of margin and base of the defects (defects were reduced and modified). The flap sizes were 7.0 cm×13.0 cm-14.0 cm×23.0 cm. After surgery, the wound healing was observed through the visits of outpatient clinic, and telephone and WeChat interviews. According to the nature of the tumours, the patients were regularly reviewed at outpatient clinic to determine the local recurrence and metastasis of the tumour.Results:One pedicled latissimus dorsi myocutaneous flap was found with a greater tension after surgery. After partial removal of sutures and dressing changes, the secondary suture was performed 1 week later and the wound healed smoothly. A postoperative venous crisis was discovered in a free ALTF. It was monitored and re-anastomosed within 24 hours after surgery, and the flap survived and the wound healed smoothly. Otherwise, the rest of flaps achieved good blood supply and the wounds at the recipient and donor sites healed in one stage. In the postoperative follow-up, all flaps in the clavicular region were found good in appearance with no obvious swelling, and the donor sites healed well without scar contracture or dysfunction. One patient with a squamous cell carcinoma died of lung metastasis at 13 months after surgery. The rest of patients were found no tumour recurrence and had completed postoperative follow-up.Conclusion:After radical resection of malignant soft tissue tumours in the clavicular region, appropriate flaps were selected according to the size (short diameter) and depth of the modified defects, as well as the skin elasticity and relaxation of the flap donor site, hence to facilitate the direct suture of the flap donor site. It not only effectively reconstructs the surgical defect in clavicular region, but also minimises the damage to the flap donor site and achieves an aesthetic appearance at the flap donor site.

Objective To compare the value of standard coronal MRI and multi-planar reconstruction(MPR)images for evaluation of anterolateral ligament(ALL).Methods Data of 130 patients who underwent knee joint MR examination were retrospectively analyzed,including standard coronal MRI and MPR images.ALL were identified on standard coronal MRI and MPR images and classified as fully visible,partially visible or invisible.The visibility of bilateral ALL on both standard coronal MRI and MPR images were compared,while Kappa test was used to evaluate the consistency on both kinds of images.Results Among 130 cases,on standard coronal MRI and MPR images,the left ALL was fully visible in 83 and 93 cases,partially visible in 21 and 12 cases but invisible cases in 26 and 25 cases,respectively,while the right side ALL was fully visible in 66 and 80 cases,partially visible cases in 29 and 15 cases but invisible cases each in 35 cases,respectively.Significant difference of visibility of bilateral ALL were found between standard coronal MRI and MPR images(both P＜0.05),both with excellent consistency(both Kappa＞0.80).Conclusion MPR could display bilateral ALL better than standard coronal MRI.If the scanning conditions for MPR could not be met,standard coronal MRI might be used to evaluate ALL rather accurately.

Objective To investigate the effects of PRPF19 knockdown on the proliferation, migration, and invasion of pancreatic cancer cells. Methods The expression of PRPF19 in pancreatic cancer and normal tissues was analyzed using the GEPIA database. The protein and mRNA expression levels of PRPF19 in pancreatic cancer cells were detected by Western blot and qRT-PCR. Small interfering RNA (siRNA) was used to silence the expression of PRPF19 in pancreatic cancer cells, and the knockdown efficiency was verified by Western blot and qRT-PCR. CCK-8, colony forming, and Transwell assay were used to detect the effects of knockdown of PRPF19 on the proliferation, colony forming, migration, and invasion of pancreatic cancer cells. Results GEPIA analysis showed that PRPF19 was highly expressed in pancreatic cancer tissues compared with normal pancreatic tissues. In comparison with normal pancreatic cells, PRPF19 was highly expressed in various pancreatic cancer cell lines such as MIA PaCa-2 and PANC-1 (P < 0.05). In comparison with the control group, PRPF19 knockdown significantly reduced the proliferation rate, colony forming, cell migration, and invasion of pancreatic cancer cells (P < 0.05). Conclusion PRPF19 knockdown inhibits the proliferation, migration, and invasion of pancreatic cancer cells. PRPF19 may play an important role as an oncogene of pancreatic cancer.

Objective: The purpose of our study was to investigate the predictive abilities of clinical and computed tomography (CT)features for outcome prediction in patients with coronavirus disease (COVID-19). Materials and Methods: The clinical and CT data of 238 patients with laboratory-confirmed COVID-19 in our two hospitalswere retrospectively analyzed. One hundred sixty-six patients (103 males; age 43.8 ± 12.3 years) were allocated in thetraining cohort and 72 patients (38 males; age 45.1 ± 15.8 years) from another independent hospital were assigned in thevalidation cohort. The primary composite endpoint was admission to an intensive care unit, use of mechanical ventilation, ordeath. Univariate and multivariate Cox proportional hazard analyses were performed to identify independent predictors. Anomogram was constructed based on the combination of clinical and CT features, and its prognostic performance wasexternally tested in the validation group. The predictive value of the combined model was compared with models built on theclinical and radiological attributes alone. Results: Overall, 35 infected patients (21.1%) in the training cohort and 10 patients (13.9%) in the validation cohortexperienced adverse outcomes. Underlying comorbidity (hazard ratio [HR], 3.35; 95% confidence interval [CI], 1.67–6.71;p < 0.001), lymphocyte count (HR, 0.12; 95% CI, 0.04–0.38; p < 0.001) and crazy-paving sign (HR, 2.15; 95% CI, 1.03–4.48;p = 0.042) were the independent factors. The nomogram displayed a concordance index (C-index) of 0.82 (95% CI, 0.76–0.88),and its prognostic value was confirmed in the validation cohort with a C-index of 0.89 (95% CI, 0.82–0.96). The combinedmodel provided the best performance over the clinical or radiological model (p < 0.050). Conclusion Underlying comorbidity, lymphocyte count and crazy-paving sign were independent predictors of adverseoutcomes. The prognostic nomogram based on the combination of clinical and CT features could be a useful tool for predictingadverse outcomes of patients with COVID-19.

Tumor vasculature is characterized by aberrant structure and function, resulting in immune suppressive profiles of tumor microenvironment through limiting immune cell infiltration into tumors, endogenous immune surveillance and immune cell function. Vascular normalization as a novel therapeutic strategy tends to prune some of the immature blood vessels and fortify the structure and function of the remaining vessels, thus improving immune stimulation and the efficacy of immunotherapy. Interestingly, the presence of "immune‒vascular crosstalk" enables the formation of a positive feedback loop between vascular normalization and immune reprogramming, providing the possibility to develop new cancer therapeutic strategies. The applications of nanomedicine in vascular-targeting therapy in cancer have gained increasing attention due to its specific physical and chemical properties. Here, we reviewed the recent advances of effective routes, especially nanomedicine, for normalizing tumor vasculature. We also summarized the development of enhancing nanoparticle-based anticancer drug delivery

Cancer immunotherapy has veered the paradigm of cancer treatment. Despite recent advances in immunotherapy for improved antitumor efficacy, the complicated tumor microenvironment (TME) is highly immunosuppressive, yielding both astounding and unsatisfactory clinical successes. In this regard, clinical outcomes of currently available immunotherapy are confined to the varied immune systems owing in large part to the lack of understanding of the complexity and diversity of the immune context of the TME. Various advanced designs of nanomedicines could still not fully surmount the delivery barriers of the TME. The immunosuppressive TME may even dampen the efficacy of antitumor immunity. Recently, some nanotechnology-related strategies have been inaugurated to modulate the immunosuppressive cells within the tumor immune microenvironment (TIME) for robust immunotherapeutic responses. In this review, we will highlight the current understanding of the immunosuppressive TIME and identify disparate subclasses of TIME that possess an impact on immunotherapy, especially those unique classes associated with the immunosuppressive effect. The immunoregulatory cell types inside the immunosuppressive TIME will be delineated along with the existing and potential approaches for immunosuppressive cell modulation. After introducing the various strategies, we will ultimately outline both the novel therapeutic targets and the potential issues that affect the efficacy of TIME-based nanomedicines.