Plant-derived extracellular vesicles (PDEVs), describe a group of nanoparticles released by plants. These particles are characterized by a lipid bilayer structure containing various proteins, lipids, nucleic acids, and unique metabolites. Although the study on PDEVs is relatively new, having only been around for ten years, they have shown promising development prospects in both basic research and clinical transformation areas. Evidence suggests that PDEVs have excellent application prospects in regulating inflammation and treating tumors. Their distinctive, vesicle-mimicking architecture and stellar biocompatibility render them prime candidates for ferrying various anti-cancer agents, including RNA, proteins, and conventional chemotherapy drugs. Increasingly, studies have shown that PDEVs can be engineered as an innovative platform for combination cancer immunotherapy. Consequently, this paper provides an extensive summary of current developments in engineering methods and strategies for PDEVs in cancer treatment and combined cancer immune therapeutics. The essential characteristics of PDEVs, including the biogenesis process and components, as well as their anti-tumor activity and mechanism, are summarized. Finally, the in vivo safety of PDEVs as delivery vectors and the challenges of scale-up production and clinical transformation are discussed.

Type 2 diabetes (T2D) is an independent risk factor for cognitive impairment. The dysregulation of hypoxia inducible factor (HIF) signaling in T2D patients results in impaired adaptive responses to hypoxia, thereby accelerating the progression of complications. However, limited knowledge is available regarding its precise function in diabetes-associated cognitive impairment (DACI). Here, elevated HIF-1α levels were observed in brain endothelial cells (ECs) of db/db mice. Functionally, brain ECs-specific knockdown of H if1 a significantly ameliorated T2D-induced memory loss and neuronal damage. Glycolysis in brain ECs was inhibited in this process, as indicated by RNA-seq, leading to decreased hippocampal lactate production through reduced LDHA expression. Notably, T2D patients showed increased cerebrospinal fluid lactate levels, which were strongly associated with their cognitive dysfunction. Intrahippocampal injection of lactate accelerated cognitive dysfunction and impaired adult hippocampal neurogenesis (AHN) in db/db mice. Conversely, reducing hippocampal lactate levels through the intrahippocampal injection of oxamate delayed the onset of memory deficits. Furthermore, asiatic acid was discovered to protect db/db mice from cognitive impairment by decreasing brain endothelial HIF-1α expression and subsequently reducing hippocampal lactate-induced AHN damage. Overall, this study elucidates the inhibiting role played by endothelial HIF-1α-driven lactate in AHN and highlights a potential tactic of targeting HIF-1α in brain ECs for treating cognitive impairment.

Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures. Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS, but the application of hydrogen has flammable and explosive safety concerns. Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance, thus improving ARDS in patients and animal models. Coral calcium hydrogenation (CCH) is a new solid molecular hydrogen carrier prepared from coral calcium (CC). Whether and how CCH affects acute lung injury in ARDS remains unstudied. In this study, we observed the therapeutic effect of CCH on lipopolysaccharide (LPS) induced acute lung injury in ARDS mice. The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable, demonstrating a significant improvement compared to the untreated ARDS model group. CCH treatment significantly reduced pulmonary hemorrhage and edema, and improved pulmonary function and local microcirculation in ARDS mice. CCH promoted mitochondrial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2 (Trx2), improved lung mitochondrial dysfunction induced by LPS, and reduced oxidative stress damage. The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

Objective To explore the value of combined prediction model based on clinical and CT radiomics features in discriminating atypical pulmonary hamartoma(APH)from atypical lung adenocarcinoma(ALA).Methods A total of 290 patients with APH and ALA confirmed by pathology were retrospectively selected.250 patients from the First Affiliated Hospital of Anhui Medical University were randomly assigned into a training set(APH=91,ALA=84)and an internal validation set(APH=39,ALA=36)at a ratio of 7∶3,and other 40 patients from the First Affiliated Hospital of USTC were assigned as an external validation set(APH=21,ALA=19).The independent model and multivariate logistic regression combined model were constructed using the selected clinical-CT features and radiomics features,respectively,and a nomogram was drawn.Receiver operating characteristic(ROC)curve and DeLong test were used to evaluate and compare the performances of the models.Results The area under the curve(AUC)of the combined model established by 3 clinical-CT features and 4 radiomics features in the training set was 0.980,which was higher than that of clinical-CT model(AUC=0.885,P＜0.001)and radiomics model(AUC=0.975,P=0.042).The AUC of the combined model in the internal and external validation sets(0.963 vs 0.917)were also higher than those of clinical-CT model(0.858 vs 0.774)and radiomics model(0.953 vs 0.897),respectively.Conclusion The combined prediction model based on clinical and CT radiomics features can improve the differential diagnosis ability of APH and ALA.

Objective To discuss the value of clinical radiomic nomogram(CRN)and deep convolutional neural network(DCNN)in distinguishing atypical pulmonary hamartoma(APH)from atypical lung adenocarcinoma(ALA).Methods A total of 307 patients were retrospectively recruited from two institutions.Patients in institu-tion 1 were randomly divided into the training(n=184:APH=97,ALA=87)and internal validation sets(n=79:APH=41,ALA=38)in a ratio of 7∶3,and patients in institution 2 were assigned as the external validation set(n=44:APH=23,ALA=21).A CRN model and a DCNN model were established,respectively,and the performances of two models were compared by delong test and receiver operating characteristic(ROC)curves.A human-machine competition was conducted to evaluate the value of AI in the Lung-RADS classification.Results The areas under the curve(AUCs)of DCNN model were higher than those of CRN model in the training,internal and external validation sets(0.983 vs 0.968,0.973 vs 0.953,and 0.942 vs 0.932,respectively),however,the differences were not statistically significant(p=0.23,0.31 and 0.34,respectively).With a radiologist-AI com-petition experiment,AI tended to downgrade more Lung-RADS categories in APH and affirm more Lung-RADS cat-egories in ALA than radiologists.Conclusion Both DCNN and CRN have higher value in distinguishing APH from ALA,with the former performing better.AI is superior to radiologists in evaluating the Lung-RADS classification of pulmonary nodules.

Objective To explore the status quo of treatment adherence and its influencing factors in community management of patients with chronic diseases in Nanjing. Methods A total of 673 patients with chronic diseases managed by community health service centers in Nanjing were selected. The general data of the study subjects were collected. MMAS-8 Scale, the Chinese version of WHQOL-BREF and PSS-Fa were used to evaluate the treatment adherence, quality of life and family support level. Pearson correlation was used to analyze the correlation between MMAS-8 score and WHQOL-BREF Chinese version and PSS-Fa score, and logistic regression analysis was used to investigate the influencing factors of treatment adherence. Results The MMAS-8 score was positively correlated with WHQOL-BREF Chinese version psychological and social management domain score and PSS-Fa score , logistic regression analysis results suggested that > 65 years of age (OR =1.723) was a risk factor for poor treatment adherence, undergraduate and above education level (OR = 0.582), annual family income > 80 000 yuan (OR = 0.603), comorbidity of chronic diseases (OR = 0.718), better overall evaluation of their own quality of life (OR = 0.547) , and high family support level (OR = 0.619) were protective factors for poor treatment adherence, and the above differences were statistically significant (P < 0.05) . Conclusion There is still room to improve the treatment adherence of patients with chronic diseases in community management in Nanjing . It is necessary to focus on elderly patients, strengthen the education of patients with single chronic diseases and improve the quality of life and family support level of patients.

Objective To compare the effects of antibiotic-loaded bone cement coverage and negative pressure wound therapy (NPWT) on diabetic foot ulcer wound healing. Methods A total of 113 patients with diabetic foot ulcers were selected as study subjects and randomly divided into control group (57 patients receiving NPWT) and experimental group (56 patients receiving antibiotic-loaded bone cement coverage) using the double-color ball randomization method. Both groups underwent routine debridement. The treatment outcomes, positive detection rate of wound bacterial culture, lower limb nerve conduction function (tibial nerve motor conduction velocity, common peroneal nerve sensory conduction velocity), Doppler ultrasound indicators (vessel diameter, blood flow velocity, resistance index, pulsatility index), inflammatory indicators (tumor necrosis factor-α, interleukin-6, high-sensitivity C-reactive protein), and granulation tissue growth were observed and compared between the two groups. Results The effective treatment rate was 85.71% in the experimental group, which was higher than 70.18% in the control group (P < 0.05). Before treatment, there were no statistically significant differences between the two groups in terms of positive detection rate of wound bacterial culture, tibial nerve motor conduction velocity, common peroneal nerve sensory conduction velocity, blood flow velocity, vessel diameter, resistance index, pulsatility index, granulation tissue growth, and serum levels of tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein (P>0.05). After 3, 7, and 15 days of treatment, the positive detection rate of wound bacterial culture in the experimental group was lower than that in the control group (P < 0.05). After treatment, the tibial nerve motor conduction velocity, common peroneal nerve sensory conduction velocity, vessel diameter, blood flow velocity, resistance index, and pulsatility index in both groups were higher or greater than those before treatment, and those in the experimental group were higher or greater than those in the control group (P < 0.05). After treatment, the granulation tissue area, coverage rate, and granulation tissue growth rate in the experimental group were higher than those in the control group (P < 0.05). After treatment, the serum levels of tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein in both groups were lower than those before treatment, and those in the experimental group were lower than those in the control group (P < 0.05). Conclusion Compared with NPWT, antibiotic-loaded bone cement coverage has a higher effective treatment rate for diabetic foot ulcers, and provides a more effective local antibacterial environment, thereby promoting wound healing and tissue repair, and simultaneously improving nerve function and vascular status.

Objective:To explore the relevant anatomical factors in the pathogenesis of chronic dacryocystitis based on CT radiomics. Methods:A retrospective analysis was conducted on the general data and sinus CT materials of 85 patients with chronic dacryocystitis（case group） admitted to our department from December 2020 to December 2023, and 85 individuals undergoing physical examination（control group） during the same period. The differences in anatomical parameters between the two groups were compared to study the morphological characteristics of the nasolacrimal duct in patients with chronic dacryocystitis. Univariate and multivariate logistic regression analyses were used to explore the relevant anatomical factors in the pathogenesis of chronic dacryocystitis. Results:There were statistically significant differences（P<0.05） in the proportion of combined nasal septal deviation, the distance between the anterior and posterior ridges of the lacrimal fossa, the angle between the long axis of the nasolacrimal duct and the projection on the midsagittal plane, the maximum transverse diameter of the bony nasolacrimal duct, the maximum cross-sectional area of the bony nasolacrimal duct, and the thickness of the frontal process of the maxilla between the two groups. There were no statistically significant differences（P>0.05） in whether there was a combined high-position nasal septal deviation, whether there was a combined non-high-position nasal septal deviation, and whether there was a combined pneumatized middle turbinate. Multivariate analysis showed that nasal septal deviation, the distance between the anterior and posterior ridges of the lacrimal fossa, the angle between the long axis of the nasolacrimal duct and the projection on the midsagittal plane, and the maximum cross-sectional area of the bony nasolacrimal duct are independent anatomical factors affecting the pathogenesis of chronic dacryocystitis. Conclusion:Nasal septal deviation, a large distance between the anterior and posterior ridges of the lacrimal fossa, a large angle between the long axis of the nasolacrimal duct and the projection on the midsagittal plane, and a small maximum transverse diameter of the bony nasolacrimal duct are important anatomical bases for the pathogenesis of chronic dacryocystitis, providing a basis for an in-depth understanding of the disease occurrence.
Humans ; Retrospective Studies ; Male ; Female ; Dacryocystitis/diagnostic imaging* ; Tomography, X-Ray Computed/methods* ; Nasolacrimal Duct/diagnostic imaging* ; Chronic Disease ; Nasal Septum/diagnostic imaging* ; Middle Aged ; Adult ; Radiomics

Objective:To investigate the application value of computed tomography (CT) and magnetic resonance imaging (MRI) examination in clinical diagnosis of gallbladder tumor with perigallbladder invasion.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 80 gallbladder tumor patients with perigallbladder invasion who were admitted to 3 medical centers (21 cases in The First Affiliated Hospital of Northwest University, 42 cases in The First Affiliated Hospital of the Air Force Medical University, 17 cases in The First Affiliated Hospital of Dalian Medical University) from January 2021 to December 2022 were collec-ted. There were 45 males and 35 females, aged (56±4)years. Observation indicators: (1) CT and MRI examinations; (2) surgical conditions. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) CT and MRI examinations. Of 80 patients, cases with gallbladder cancer and gallbladder adenoma were 73 and 7, respectively. Cases with endoluminal nodular type, mass type and localized thick-walled type were 33, 39 and 8, respectively, with tumor diameter as 1.55 cm×1.35 cm×1.33 cm, 1.64 cm×1.37 cm×1.36 cm and 5.72 cm×4.07 cm×4.36 cm. Results of CT examination of endoluminal nodular type showed local nodular protrusions into the endoluminal area, and local enhancement on enhanced scanning. Results of CT examination of localized thick-walled type showed the cavity wall of lesion was locally or diffusely irregul-arly thickened, with a thickness of 1.10(range, 1.10-2.21)cm. Of 80 patients, results of CT and MRI examinations showed invasion of liver parenchyma in 68 cases, which was manifested as local mass, blurred demarcation, and abnormal protrusion. The maximum depth was (4.22±0.25)cm, (4.22±0.22)cm, (4.28±0.16)cm of cross-sectional, coronal, sagittal view in CT examination, respectively. The minimum depth was (0.22±0.10)cm, (0.25±0.08)cm, (0.24±0.12)cm. The depth of liver parenchyma invaded was (1.64±1.38)cm, (1.68±1.46)cm, (1.66±1.40)cm. Results of CT and MRI examinations showed invasion of perigallbladder, which was manifested as local invasion of the gastric antrum in 12 cases. (2) Surgical conditions. Of 80 patients, results of CT and MRI examina-tions showed that 60 patients had localized masses in the gallbladder cavity with or without infiltration of surrounding tissues. After confirming the absence of other organs and distant metastasis, cases undergoing radical resection and palliative resection were 44 and 16, respectively. Results of CT and MRI examina-tions showed that 20 patients had malignant gallbladder tumors with peri-pheral liver infiltration and multiple intrahepatic metastases with distant organ metastases, which were unresectable.Conclusion:For patients with gallbladder cancer and perigallbladder invasion, CT or MRI examina-tions can show their structural characteristics.

BACKGROUND: Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction. OBJECTIVE: This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale. METHODS: This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment. DISCUSSION This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).
Humans ; ST Elevation Myocardial Infarction/therapy* ; Stroke Volume ; Ventricular Remodeling ; Prospective Studies ; Microcirculation ; Ventricular Function, Left ; Myocardial Infarction/etiology* ; Treatment Outcome ; Percutaneous Coronary Intervention/adverse effects* ; Heart Failure/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic