Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.

ObjectiveThe objective is to investigate the possibility of isocenter dual-guided resetting of surface guided radiation therapy （SGRT） combined with image guided radiation therapy （IGRT） in postoperative radiotherapy for breast cancer. To assess the setup error accuracy between the new resetting mode and the traditional resetting mode. MethodsRetrospective analysis was performed on breast cancer patients who underwent ELEKTA infinity accelerator radiotherapy in sun yat-sen university cancer center from July 13， 2021 to October 15， 2022. According to different reset methods， the patients were divided into a simulation group （41 cases） and a dual-guided group （40 cases）. The simulation group was reset using a simulator， CBCT scans were performed and setup errors were recorded during the first treatment； The dual-guided group was guided by AlignRT and combined with CBCT for isocenter dual-guided resetting， and the setup error obtained by CBCT registration was recorded. The global setup errors of chest region of interest （CROI） ， the local residual errors of supraclavicular region of interest （SROI） and the resetting time of the two reset methods were calculated and compared respectively. The advantages of the CBCT error distribution in the dual-guided resetting of SGRT combined with IGRT were analyzed. ResultsThe median of the global setup errors （X/cm， Y/cm， Z/cm， Rx°， Ry°， Rz°） of the simulation group and the median of the dual-guided group in the CROI were statistically significant （P<0.05） except the Rz and Ry directions. The local residual errors of the two groups of the SROI were calculated. The median of the errors of X/cm， Y/cm， Z/cm， Rx°， Ry°， Rz° were statistically significant （P<0.05） except the X and Y axis. The resetting time of the simulation group was significantly longer than that of the dual-guided group （238.64±28.56） s， t=-24.555， P=0.000， and the difference was statistically significant （P<0.05）. The CBCT error distribution of the dual-guide group was analyzed， and it was found that the absolute values of translation errors of X， Y and Z axis were all within 0.4 cm， while the proportions of ≤ 0.3 cm were 95%， 93% and 93%， respectively. The proportions of rotation errors of Rx， Ry and Rz ≤ 1.5 ° were 90%， 93% and 90%， respectively. ConclusionIn postoperative radiotherapy of breast cancer， SGRT combined with IGRT for isocenter dual-guided resetting can effectively correct the rotational setup errors and residual errors， and improve the accuracy of radiotherapy with less resetting time and high feasibility， which compared with the traditional simulator resetting mode. This precise， unmarked resetting method can be widely used in clinical practice.

The rise of nanotechnology has opened new horizons for cancer immunotherapy. However, most nanovaccines fabricated with nanomaterials suffer from carrier-related concerns, including low drug loading capacity, unpredictable metabolism, and potential systemic toxicity, which bring obstacles for their clinical translation. Herein, we developed an antigen self-assembled nanovaccine, which was resulted from a simple acryloyl modification of the antigen to induce self-assembly. Furthermore, a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid (Zol) were integrated or absorbed onto the nanoparticles (denoted as MEAO-Z) to intensify the immune response. The synthesized nanovaccine with a diameter of around 70 nm showed successful lymph node transportation, high dendritic cell internalization, promoted costimulatory molecule expression, and preferable antigen cross-presentation. In virtue of the above superiorities, MEAO-Z induced remarkably higher titers of serum antibody, stronger cytotoxic T lymphocyte immune responses and IFN-γ secretion than free antigen and adjuvants. In vivo, MEAO-Z significantly suppressed EG7-OVA tumor growth and prolonged the survival time of tumor-bearing mice. These results indicated the translation promise of our self-assembled nanovaccine for immune potentiation and cancer immunotherapy.

Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic.

OBJECTIV E To investigate the effect s and mechanism of the ethanol extract of Tiarella polyphylla （“TPE”）on learning and memory impairment in mice. METHODS Male Kunming mice were randomly divided into normal group ，model group，positive group （donepezil hydrochloride 4 mg/kg）and TPE low-dose ，medium-dose and high-dose groups （150，300，600 mg/kg），with 10 mice in each group. Drug administration groups were given relevant medicine intragastrically once a day ，and normal group and model group were given water intragastrically once a day ，for consecutive 22 d. On the 17th day ，administration groups and model group were intraperitoneally injected with scopolamine hydrobromide （3 mg/kg）to establish a model of learning and memory impairment. The learning and memory ability of the mice were evaluated by the Morris water maze. Hematoxylin-eosin （HE） staining was used for morphological observation of hippocampus cells of the mice. The levels of acetylcholinesterase （AChE），choline acetyltransferase （ChAT），superoxide dismutase （SOD），malondialdehyde（MDA），interleukin-6（IL-6）and tumor necrosis factor-α（TNF-α）in cerebral tissue as well as the relative expression of phosphorylated Tau protein （p-Tau），β-site amyloid precursor protein cleaving enzyme 1（BACE1）and amyloid precursor protein （APP）in hippocampus tissue were all detected. RESULTS The escape latency of mice in positive group ，TPE medium-dose and high-dose groups were all significantly shortened than the model group on the 4th to 5th day of training ，while the times of crossing platform and the percentage of movement distance in target quadrant were significantly increased （P＜0.05）. Compared with model group ，the neurons in the hippocampal CA 1 region of mice were increased to var ying degrees in administration groups ，the ne urons in solidified and atrophic state decreased ，and the arrangement of neurons tended to be close；the levels of ChAT and SOD in cerebral tissue were significantly increased in positive group and TPE medium-dose and high-dose groups ；the levels of AChE ，MDA，IL-6，the levels of TNF-α and relative expression of p-Tau ，BACE1 and APP in hippocampus tissue were decreased significantly （P＜ 0.05）. CONCLUSIONS TPE can improve the learning and memory impairment induced by scopolamine in mice ，and the mechanism may be related to balancing the brain cholinergic system ，alleviating oxidative stress injury ，improving inflammatory response，and inhibiting the overexpression of p-Tau ，BACE1 and APP .

Objective To explore olanzapine effect on the cognitive function and neuronal damage of aged schizophrenic rats based on the PI3 K/Akt signaling pathway. Methods Ten-week-old SD rats were randomly divided into a blank control group（n=12） and a modeling intervention group（n=48）. The modeling group were injected with didroxapine maleate [MK-801,0.2 mg/（kg·d）] for 14 days. And the model was evaluated by general behavioral studies to determine the success of model building. The model rats were randomly divided into model group and low, medium, and high dose olanzapine groups [10, 20, 40 mg/（kg·d）], each with 12 rats. The control group and model group were given distilled water; the low, medium, and high dose olanzapine groups were given olanzapine for 21 days. The stereotyped lines were scored by the standard of Sams Dodd and Hoffman, the cognitive evaluation of the rats was performed by the Morris water maze, and the levels of interleukin-6（IL-6） and tumor necrosis factor-α（TNF-α） in the serum were determined by ELISA. The activities of dihydrokaempferol（Ach） and acetyl cholinesterase（AchE）in brain tissue were detected by acetylcholinesterase activity assay kit. Rat brain tissue PI3 K, Akt, mammalian target of rapamycin（mTOR） mRNA expression levels were detected by Real-time PCR. Results Compared with the model group, the stereotyped behavior and ataxia scores, escape latency, number of crossing platforms, serum levels of IL-6, TNF-α, AchE, phosphorylated PI3 K（p-PI3 K）, phosphorylated Akt（p-Akt） protein expression decreased（P＜0.05 or P＜0.01）, while brain tissue Ach, PI3 K, mTOR and phosphorylated mTOR（p-mTOR） protein content increased（P＜0.05 or P＜0.01） in the low, medium and high dose olanzapine groups. The content of Akt was increased in the low-dose group. Compared with the model group, Akt and mTOR mRNA in the brain tissue of rats in the low, medium, and high-dose alanzapine groups expression levels were down-regulated（P＜0.05 or P＜0.01）. PI3 K mRNA in the brain tissue of rats in the low, medium, and high-dose alanzapine groups expression levels were down-regulated（P＜0.05 or P＜0.01）. Conclusion Olanzapine can reduce stereotyped behavior and ataxia scores, escape latency, number of crossing platforms, IL-6, TNF-α, AchE and increase Ach content and regulate the PI3 K/Akt signaling pathway to relieve the schizophrenia.

Objective:To analyze the incidence and epidemiological characteristics of traumatic spinal cord injury in China in 2018.Methods:Multi-stage stratified cluster sampling was used to randomly select hospitals capable of treating patients with spinal cord injury from 3 regions，9 provinces and 27 cities in China to retrospectively investigate eligible patients with traumatic spinal cord injury admitted in 2018. National and regional incidence rates were calculated. The data of cause of injury，injury level，severity of injury，segment and type of fracture，complications，death and other data were collected by medical record questionnaire，and analyzed according to geographical region，age and gender.Results:Medical records of 4，134 patients were included in this study，with a male-to-female ratio of 2.99∶1. The incidence of traumatic spinal cord injury in China in 2018 was 50.484 / 1 million （95% CI 50.122-50.846）. The highest incidence in the Eastern region was 53.791 / 1 million （95% CI 53.217-54.365）. In the whole country，the main causes of injury were high falls （29.58%），as well as in the Western region （40.68%），while the main causes of injury in the Eastern and Central regions were traffic injuries （31.22%，30.10%）. The main injury level was cervical spinal cord in the whole country （64.49%），and the proportion of cervical spinal cord injury in the Central region was the highest （74.68%），and the proportion of lumbosacral spinal cord injury in the Western region was the highest （32.30%）. The highest proportion of degree of injury was incomplete quadriplegia （55.20%），and the distribution pattern was the same in each region. A total of 65.87% of the patients were complicated with fracture or dislocation，77.95% in the Western region and only 54.77% in the Central region. In the whole country，the head was the main combined injury （37.87%），as well as in the Eastern and Central regions，while the proportion of chest combined injury in the Western region was the highest （38.57%）. A total of 32.90% of the patients were complicated with respiratory complications. There were 23 patients （0.56%） died in hospital，of which 17（73.91%） died of respiratory dysfunction. Conclusions:The Eastern region of China has a high incidence of traumatic spinal cord injury. Other epidemiological features include high fall as the main cause of injury cervical spinal cord injury as the main injury level，incomplete quadriplegia as the main degree of injury，head as the main combined injury，and respiratory complications as the main complication.

Objective:To explore the antidepressant mechanism of Yinxing Mihuan oral solution （YMO） by investigating its effect on depression model rats. Method:The depression rats were induced by isolation combined with chronic unpredictable mild stress （CUMS） and then randomly divided into model group， fluoxetine group （10 mg·kg^-1） and high-dose （618 mg·kg^-1） and low-dose （309 mg·kg^-1） YMO groups. A blank control group was also set up and ten rats were included in each group. Modeling lasted for 21 consecutive days， and rats were administered the 8th day after stimulation at a dose of 10 mL·kg^-1 for 14 days， except those in the blank control and model groups which were given distilled water. Afterward， the sucrose preference test， open field test， tail suspension test were carried out. The pathological changes of hippocampus in depression rats were observed after hematoxylin-eosin （HE） staining. The content of interleukin-1β （IL-1β）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in the hippocampus of rats in each group and the expression of NOD-like receptor 3 （NLRP3） and other proteins in its related activation signaling pathways were detected with multi-factor detection （Luminex） and Western blot. Result:After 14 days of continuous administration， compared with the blank control group， the model group witnessed significantly reduced sugar water consumption rate and the times of rearing and significantly prolonged cumulative time of immobility during tail suspension （P<0.05， P<0.01）. Compared with the model group， the fluoxetine group and the high-dose YMO group saw increases in the times of rearing， times of crossing and sugar water consumption rate and a significant decrease in the cumulative time of immobility during tail suspension （P<0.05， P<0.01）. The results of HE staining showed that the neurons in the hippocampus of rats in the high-dose YMO group were arranged in order and slightly loosened， without obvious microglia infiltration observed. The levels of IL-1β， IL-6 and TNF-α in the hippocampus of the model group increased significantly as compared with the blank control group （P<0.05， P<0.01）， and their content in the high-dose YMO group was significantly lowered in the comparison with the model group （P<0.05， P<0.01）. Molecular biology experiments demonstrated that compared with the results of blank group， the expression of purinergic receptor P2X7 （P2RX7）， NLRP3， apoptosis-associated speck-like protein （ASC）， Caspase-1 and IL-1β remarkably increased in the model group （P<0.05， P<0.01）. Additionally， the expression of P2RX7， NLRP3， ASC， Caspase-1 and IL-1β was significantly inhibited in the fluoxetine group and the high-dose YMO group compared with the model group （P<0.05， P<0.01）. Conclusion:YMO can improve the depression-like behaviors of rats induced by isolation combined with CUMS， and its mechanism of action is related to the regulation of the P2RX7/NLRP3 signaling pathway.

Objective:To systematically evaluate the changes of serum nitric oxide (NO) content in adult patients with Kaschin-Beck disease (KBD).Methods:Systematic retrieval was conducted on China National Knowledge Infrastructure (CNKI), WanFang Data, VIP Database, PubMed, Embase and other databases, to analyze the literatures published from the database establishment to March 31, 2019, on the changes of serum NO content of adult patients with KBD. Meta-analysis was performed using Revman 5.3 software, and mean difference ( MD) and 95% confidence interval ( CI) were calculated; sensitivity analysis was performed using fixed-effect model or random-effect model based on heterogeneity results; and publication bias was evaluated using funnel chart. Results:Totally 7 qualified literatures were included, including 358 cases in the adult KBD group and 305 cases in the control group. After the heterogeneity test, there was heterogeneity among the literatures (χ 2 = 188.07, I2 = 97%, P < 0.01), so a random-effect model was used for Meta-analysis. The NO content in the KBD group was significantly higher than that in the control group (MD = 44.29, 95% CI: 30.57 - 58.00), the difference was statistically significant ( Z = 6.33, P < 0.01). Sensitivity analysis showed that the results of this study were stable. The two sides of the funnel were basically symmetrical, suggesting that the possibility of publication bias was small. Conclusion:The serum level of NO content in adult patients with KBD is significantly increased.

Objective: To analyze the clinical characteristics of cases of novel coronavirus pneumonia and a preliminary study to explore the relationship between different clinical classification and liver damage. Methods: Consecutively confirmed novel coronavirus infection cases admitted to seven designated hospitals during January 23, 2020 to February 8, 2020 were included. Clinical classification (mild, moderate, severe, and critical) was carried out according to the diagnosis and treatment program of novel coronavirus pneumonia (Trial Fifth Edition) issued by the National Health Commission. The research data were analyzed using SPSS19.0 statistical software. Quantitative data were expressed as median (interquartile range), and qualitative data were expressed as frequency and rate. Results: 32 confirmed cases that met the inclusion criteria were included. 28 cases were of mild or moderate type (87.50%), and four cases (12.50%) of severe or critical type. Four cases (12.5%) were combined with one underlying disease (bronchial asthma, coronary heart disease, malignant tumor, chronic kidney disease), and one case (3.13%) was simultaneously combined with high blood pressure and malignant tumor. The results of laboratory examination showed that the alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBil) for entire cohort were 26.98 (16.88 ~ 46.09) U/L and 24.75 (18.71 ~ 31.79) U/L, 39.00 (36.20 ~ 44.20) g/L and 16.40 (11.34- ~ 21.15) mmol/L, respectively. ALT, AST, ALB and TBil of the mild or moderate subgroups were 22.75 (16.31- ~ 37.25) U/L, 23.63 (18.71 ~ 26.50) U/L, 39.70 (36.50 ~ 46.10) g/L, and 15.95 (11.34 ~ 20.83) mmol/L, respectively. ALT, AST, ALB and TBil of the severe or critical subgroups were 60.25 (40.88 ~ 68.90) U/L, 37.00 (20.88 ~ 64.45) U/L, 35.75 (28.68 ~ 42.00) g/L, and 20.50 (11.28 ~ 25.00) mmol/L, respectively. Conclusion The results of this multicenter retrospective study suggests that novel coronavirus pneumonia combined with liver damage is more likely to be caused by adverse drug reactions and systemic inflammation in severe patients receiving medical treatment. Therefore, liver function monitoring and evaluation should be strengthened during the treatment of such patients.