BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

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.

ObjectiveTo explore the feasibility and rationality of applying relevant diagnostic and treatment programmes from textbooks as evidence in traditional Chinese medicine （TCM） diagnosis and treatment guidelines， using allergic rhinitis as an example. MethodsTextbooks published from October 1949 to December 2022， as well as TCM diagnosis and treatment guidelines published until December 2022 on allergic rhinitis were searched， and the contents of diagnosis and treatment related to allergic rhinitis were extracted. The similarities and differences between textbooks in different periods， between textbooks in different versions， and between textbooks and guidelines were compared and analyzed. ResultsA total of 12 national planning textbooks on TCM otolaryngology and 4 Chinese medicine diagnosis and treatment guidelines on allergic rhinitis from 1975 to 2021 were included. The evolution of diagnostic and treatment programmes was shown by the textbooks in different periods. Since 2003， syndrome of latent heat in lung channel has been added in the published textbook， and TCM featured therapies， such as nasal packing， intranasal spray were enriched， as well as the contents related to prevention and prognosis. The main syndromes included lung qi deficiency and cold， spleen qi deficiency， kidney yang deficiency， and latent heat in lung meridian. The most common recommended prescriptions were Wenfei Zhiliu Pill （温肺止流丹）， Yupingfeng Powder （玉屏风散） and Cangerzi Powder （苍耳子散）； Buzhong Yiqi Decoction （补中益气汤）， Shenling Baizhu Powder （参苓白术散）； Shenqi Pill （肾气丸） or Zhenwu Decoction （真武汤）； Xinyi Qingfei Decoction （辛夷清肺饮）. A comparison of different versions of textbooks showed that the classification of syndromes was consistent， while the formulas were slightly different. The comparison between different versions of the current textbooks and the guidelines showed that the recommended prescriptions of the textbooks had more Cangerzi Powder， Xiaoqinglong Decoction （小青龙汤）， Zhenwu Decoction， etc.， while TCM featured therapies such as nose blowing， smelling， nasal plugging， nasal washing were enriched， and information on formula modification， prevention and adjustment， prognosis were also added， which can supplement the corresponding evidence for the guidelines. ConclusionTextbooks could serve as a strong supplement for the evidence-based development of TCM clinical guidelines. However， there is still a need for further research on the quality assessment system of textbook evidence to improve the credibility of its applicability of the guidelines evidence.

Objective To optimize the formulation and preparation process of lenvatinib mixed micelles.Methods Hybrid micelles of lenvatinib were prepared by film hydration method,with Pluronic P123 and F127 as carrier materials.Optimal formulation was selected through single-factor experiments and central composite design-response surface methodology,and preliminary characterization of its physical properties was conducted.Results The optimized formulation and process conditions were identified as follows:P123 mass percentage of 80%,carrier material amount of 90 mg,drug loading of 10 mg,hydration volume of 6 ml,hydration time of 45 min,and rotary evaporation temperature of 55℃.The resulting lenvatinib mixed micelles had an average particle size of(104.0±0.32)nm,a polydispersity index(PDI)of 0.22±1.19,and a Zeta potential of(-2.56±0.81)mV.The average encapsulation efficiency was 83.33%±0.30%and the average drug loading was 8.67%±0.07%.The micelles displayed a uniform spherical morphology with a certain sustained-release capability.Conclusion The preparation process developed in this study was simple and feasible and produced drug-loaded micelles with high drug loading and encapsulation rates,and stable release,which could provide valuable insights for further research and development of lenvatinib mixed micelles.

Objective:Using ultrasound imaging technology to evaluate the contraction characteristics of diaphragm in patients with chronic low back pain.Methods:Twenty nine patients with chronic low back pain and 26 healthy persons recruited from the rehabilitation department of the Third Affiliated Hospital of Sun Yat-sen University from November 2019 to April 2020 were selected and divided into the low back pain (LBP) group and the healthy control group. The thickness of the diaphragm (Tdi) of the subjects during deep breathing was evaluated by portable color Doppler ultrasound equipment under different body positions. The subjects were required to perform maximum inspiration for total lung capacity (TLC) and expiration for functional residual capacity (FRC) in the supine and standing position, respectively. The end-inspiratory diaphragm thickness (TdiTLC) and end-expiratory diaphragm thickness (TdiFRC) were recorded, and the diaphragmatic thickening fraction (DTF) was calculated. The general data of subjects with lower back pain and the correlation between Oswestry Dysfunction Index (ODI) and diaphragm function were analyzed; The diaphragm function of healthy control group and LBP group were compared; The receiver operating characteristic (ROC) curve of Tdi and DTF in the diagnosis of lower back pain were analyzed.Results:ODI lifting score was negatively correlated with standing TdiTLC ( r=-0.50, P<0.01). In intra-group comparison, the TdiTLC and TdiFRC values of healthy subjects in standing position were increased compared with those in supine position ( t=6.115, 7.314, all P<0.001); In standing position, TdiTCL and TdiFRC values in LBP group were increased compared with those in supine position ( t=2.834, 4.673, all P<0.01). In comparison between groups, TdiTLC values in supine and standing position of LBP group were significantly lower than those in healthy control group ( t=2.597, 3.338, all P<0.05); In standing position, TdiFRC of patients in LBP group was significantly lower than that of healthy control group ( t=2.098, P=0.041) and DTF value of patients in LBP group was significantly lower than that of healthy control group ( t=2.902, P=0.006). When TdiTCL≤3.3 mm in supine position was used to predict low back pain, the diagnostic sensitivity and specificity were 78.6% and 53.8%, respectively, and the area under the curve was 0.661. When TdiTCL≤4.5 mm in standing position was used to predict low back pain, the diagnostic sensitivity and specificity were 95.7% and 46.2%, respectively, and the area under the curve was 0.759. When DTF≤81.3% in standing position was used to predict low back pain, the diagnostic sensitivity and specificity were 52.2% and 84.6%, respectively, and the area under the curve was 0.698. Conclusions:It is found in our study that the diaphragm contractile function of patients with lower back pain is worse than that of normal subjects, and the difference was significant in standing position. We suggest that the right-side ultrasound image acquisition in the patient′s standing position is helpful to ensure the accuracy and objectivity of the measurement results. TdiTCL≤4.5 mm or DTF≤81.3% in standing position can be used as one of the reference indexes for the combined diagnosis of chronic low back pain.

Objective:To assess the cost-effectiveness of influenza vaccination among people aged 60 years and older in Shenzhen.Methods:A Markov state transition model was constructed to evaluate the cost-effectiveness of annual influenza vaccination for preventing influenza infection compared with no vaccination among the elderly from the social perspective. Allowing seasonal variation of influenza activity, the model followed a five-year cohort using weekly cycles. We employed once the Chinese gross domestic product (GDP) per capita in 2019 (70 892 yuan) as the willingness-to-pay (WTP) threshold and calculated the net monetary benefit (NMB) with costs and quality-adjusted life-years (QALYs) discounted at 5% annually. The impact of parameter uncertainty on the results was examined using one-way and probabilistic sensitivity analyses (PSA).Results:The base case amounted to approximately 35 yuan of cost-saving and a net gain of 0.007 QALYs. Correspondingly, the NMB was 529 yuan per vaccinated person. One-way sensitivity analyses showed that the NMB was relatively sensitive to changes in the attack rate of influenza and vaccine effectiveness. Based on the results of PSA with 1 000 Monte Carlo simulations, influenza vaccination had a probability of being cost-effective in 100% of the repetitions.Conclusions:The present study provides evidence that influenza vaccination is a cost-saving disease prevention strategy for people aged 60 years and older in Shenzhen.

Objective:To evaluate the relationship between intraoperative concentration of C-X-C motif chemokine 13 (CXCL13) in peripheral blood and postoperative delirium (POD) in elderly patients under general anesthesia.Methods:Ninety-three patients of both sexes, aged 65-85 yr, of American Society of Anesthesiologists physical statusⅠor Ⅱ, scheduled for elective hip replacement under general anesthesia, were selected.Peripheral venous blood samples were collected to determine the concentrations of CXCL13 and interleukin-6 (IL-6) before anesthesia and during surgery (30 min after skin incision). The Confusion Assessment Method Scale in Chinese was used to detect the development of POD every day within 7 days after surgery in 2 groups.The patients were divided into POD group and non-POD group.Logistic regression analysis was used to identify the risk factors for POD.Results:Seventeen patients developed POD (19%). There was significant difference in ages, preoperative mini-mental state examination (MMSE) scores before surgery, hospital stay time and intraoperative concentrations of CXCL13 and IL-6 in peripheral blood between group non-POD and group POD ( P<0.05). The results of logistic regression analysis showed that preoperative MMSE scores, intraoperative concentrations of CXCL13 and IL-6 in peripheral blood and advanced ages were independent risk factors for the development of POD ( P<0.05). Conclusion:Preoperative MMES scores, intraoperative concentrations of CXCL13 and IL-6 in peripheral blood and advanced ages are independent risk factors for the development of POD.

Objective:To evaluate the effect of edaravone on long-term cognitive function in elderly patients undergoing hip replacement.Methods:A total of 160 patients, aged≥65 yr, undergoing elective hip replacement, were divided into 2 groups ( n=80 each) using the random sequence generated by the McLeod-modified Wichmann-Hill pseudo-random number generator: edaravone group (group E) and control group (group C). Spinal-epidural anesthesia was applied in two groups.Edaravone 60 mg (in 100 ml of normal saline, infusion rate 200 ml/h) was intravenously infused from the time point immediately after achieving the anesthesia plane until the following 30 min.Serum chemokine ligand 13 (CXCL13) and interleukin-6 (IL-6) concentrations were detected by enzyme-linked immunosorbent assay before anesthesia, during surgery (30 min after skin incision), and at postoperative days 1, 3 and 7.The Confusion Assessment Method Scale in Chinese was used to detect the postoperative delirium at postoperative days 1, 2, 3 and 7, and the Telephone Interview for Cognitive Status-Modified and ADL score were adopted to assess the cognitive function and quality of daily living, respectively, and the occurrence of cognitive impairment was recorded at 1 and 12 months after surgery. Results:Compared with group C, the total Telephone Interview for Cognitive Status-Modified score and ADL score were significantly increased, the incidence of postoperative delirium and cognitive impairment was decreased, and the serum CXCL13 and IL-6 concentrations were decreased during surgery and at each time point after surgery in group E ( P<0.05). Conclusion:Edaravone can reduce inflammatory responses and improve long-term cognitive function in elderly patients undergoing hip replacement.

Objective:To investigate the knowledge of the disease and demands of medical intervention in high-risk individuals of arteriosclerotic cardiovascular diseases (ASCVD).Methods:The 10-year ASCVD incidence risk prediction model was used to screen ASCVD high-risk individuals from Luohu district of Shenzhen city. From October 2018 to April 2019,a semi-structured in-depth interview was conducted among ASCVD high-risk individuals selected by stratified sampling method according to age, gender and educational level. The original data were analyzed with Colaizzi′s seven-step analysis method.Results:Total 37 interviewees were enrolled with an average age of (65.2±8.9) years and with an average ASCVD risk value of (14.2±3.2). Three themes were extracted from the interview, including: (1) Majority interviewees had better Knowledge about the hazards and risk factors of ASCVD; (2) Most of the interviewees had lower medical demands; (3) The interviewees were more likely to focus on symptomatic diseases or diseases disturbing them.Conclusions:The asymptomatic high-risk ASCVD individuals generally have better awareness of ASCVD and less demands for intervention. The result indicates that for health education, not only the knowledge, but also the attitude and behavior should be enhanced.