The present study employed UPLC-MS/MS to analyze and identify compounds in the raw powder of Tongluo Shenggu capsules. An HPLC method for the determination of vitexin content was established. The analysis of this drug was performed on a 30 ℃ thermostatic Acquity UPLC® BEH C18 (2.1 mm×100 mm,1.7 μm) column, with the mobile phase comprising 0.2% formic acid-methanol flowing at 0.3 mL /min in a gradient elution manner. Mass spectrometry was detected by ESI sources in both positive and negative ion modes for qualitative identification of chemical constituents. 12 flavonoid and 3 stilbenes compounds in the raw powder of Tongluo Shenggu capsules were successfully identified. Additionally, an HPLC method for the determination of vitexin content was established using a XBridge C18 column (4.6 mm × 250 mm, 5 µm) with a mobile phase of 0.05% glacial acetic acid in methanol for gradient elution, at a column temperature of 30 °C, a flow rate of 1.0 mL/min, and an injection volume of 20 μL. The method demonstrated good linearity in the concentration range of 10 µg/mL to 40 µg/mL (R=1.000) with an average recovery rate of 96.7%. The establishment of these methods provides a scientific basis for the quality control and development of the raw powder of Tongluo Shenggu capsules.

Objective To Explore the feasibility and value of deep learning technology for quality control of echocardiography images.Methods A total of 180985 echocardiography images collected from Sichuan Provin-cial People's Hospital between 2015 and 2022 were selected to establish the experimental dataset.Two task models of the echocardiography standard views quality assessment method were trained,including intelligent recognition of seven types of views(six standard views and other views)and quality scoring of six standard views.The predictions of the models on the test set were compared with the results of the sonographer's annotation to assess the accuracy,feasibility,and timeliness of the runs of the two models.Results The overall classification accuracy of the stan-dard views recognition model was 98.90%,the precision was 98.17%,the recall was 98.18%and the F1 value was 98.17%,with the classification results close to the expert recognition level;the average PLCC of the six standard views quality scoring models was 0.933,the average SROCC was 0.929,the average RMSE was 7.95 and the average MAE was 4.83,and the prediction results were in strong agreement with the expert scores.The single-frame inference time after deployment on the 3090 GPU was less than 20 ms,meeting real-time requirements.Conclusion The echocardiography standard views quality assessment method can provide objective and accurate quality assessment results,promoting the development of echocardiography image quality control management towards real-time,objective,and intelligent.

BACKGROUND:Sarcopenia is a progressive,generalized skeletal muscle disease that is closely related to the occurrence of osteoarthritis,fractures,limb disability and death in the elderly.Establishing animal models of sarcopenia is essential to understand the pathophysiology of sarcopenia and to identify effective treatment strategies. OBJECTIVE:To review the evaluation criteria of mouse models of sarcopenia and the modeling methods of mouse models of sarcopenia,and to analyze and compare the advantages and disadvantages of various modeling methods,in order to provide reference for the research and diagnosis and treatment of sarcopenia. METHODS:"Sarcopenia,skeletal muscle aging,mouse model,animal model"in Chinese and English were used as Chinese and English search terms,respectively.The search formula was"(sarcopenia OR skeletal muscle aging)AND(mouse model OR animal model)."CNKI,WanFang and PubMed were searched for related articles published from January 2010 and October 2022.A total of 59 articles were finally included for analysis. RESULTS AND CONCLUSION:There is a faster modeling time in SAMP8 mice and the type of muscle atrophy is consistent with that of patients with sarcopenia.Therefore,it is an ideal model.Although the surgical method can successfully induce muscle atrophy,it requires precise surgical operation,which is difficult and time-consuming.Hindlimb suspension modeling in mice is similar to that of the elderly and can be regarded as an effective model of senile sarcopenia.Although reagent injection molding is simple to perform,both the dose and number of days of administration of reagents are not clear and need to be further investigated.Transgenic mouse models are less commonly used and their model stability needs further study.The search for a mouse model with low cost,short time consumption and high simulation of human sarcopenia is still a future research direction.

The heat shock protein 90 (Hsp90) protein family is a cluster of highly conserved molecules that play an important role in maintaining cellular homeostasis. Hsp90 and its co-chaperones regulate a variety of pathways and cellular functions, such as cell growth, cell cycle control and apoptosis. Hsp90 is closely associated with the occurrence and development of tumors and other diseases, making it an attractive target for cancer therapeutics. Inhibition of Hsp90 expression can affect multiple oncogenic pathways simultaneously. Most Hsp90 small molecule inhibitors are in clinical trials due to their low efficacy, toxicity or drug resistance, but they have obvious synergistic anti-tumor effect when used with histone deacetylase (HDAC) inhibitors, tubulin inhibitors or topoisomerase II (Topo II) inhibitors. To address this issue, the design of Hsp90 dual-target inhibitors can improve efficacy and reduce drug resistance, making it an effective tumor treatment strategy. In this paper, the domain and biological function of Hsp90 are briefly introduced, and the design, discovery and structure-activity relationship of Hsp90 dual inhibitors are discussed, in order to provide reference for the discovery of novel Hsp90 dual inhibitors and clinical drug research from the perspective of medicinal chemistry.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Objective To investigate the effect of melanoma associated antigen D1 (Mage-D1)on mouse femoral bone mass and mineralization ability of mouse bone marrow mesenchymal cells (BMSCs)and its potential molecular mechanism.Methods Female Mage-D1 gene knockout heterozygous mice and male wild-type (WT)mice were subjected as parent mice to breed Mage-D1 gene knockout homozygous (Mage-D1 KO)mice.PCR and agarose gel electrophoresis were used to identify male Mage-D1 knockout (Mage-D1 KO)mice and littermate male wild-type (WT)mice.Micro-CT scanning was performed to observe mouse femoral bone mass,and ELISA and chemical assay were employed to detect serum levels of calcium,phosphorus,calcitonin,and parathyroid hormone in mice.After primary cultured BMSCs were identified with flow cytometry,immunofluorescence staining was utilized to detect the expression of Mage-D1 in BMSCs.BMSCs were infected by Mage-D1 silencing lentivirus,and then the cells were divided into negative control group (sh-NC)and silencing group (sh-Mage-D1).Cell scratch assay was conducted to detect the migration ability of BMSCs,and flow cytometry and CCK-8 assay were conducted to detect the cycle change and proliferation ability of BMSCs.After mineralization induction,alkaline phosphatase (ALP) staining and alizarin red staining were performed;RT-qPCR and Western blotting were used to measure the expression levels of ALP,Runx2 and Col1.RT-qPCR was used to detect mineralization-related genes p75NTR and Msx1.Results Compared with the WT mice,the femoral cortical bone thickness,cortical bone mineral content,cancellous bone mineral content,trabecular number,and cancellous bone surface density were decreased,and trabecular separation was increased in the Mage-D1 knockout homozygous mice (P<0.05).There were no significant changes in the serum levels of calcium,phosphorus,calcitonin and parathyroid hormone in mice after Mage-D1 knockout.Mage-D1 was expressed in the whole BMSCs and was highly expressed in the nucleus and perinuclear regions.Compared with the sh-NC BMSCs,the sh-Mage-D1 group had decreased proliferation ability (P<0.01),enhanced migration ability (P<0.01),and decreased expression of ALP,Runx2 and Col1 genes (P<0.05)and protein (P<0.01)after mineralization induction,milder ALP and alizarin red stain,and lower expression levels of p75NTR and Msx1.Conclusion Mage-D1 knockout can significantly reduce femur bone mass in mice.It can promote the proliferation and inhibit migration of BMSCs,and positively regulate their mineralization in vitro,and the p75NTR-Dlx1/Msx1 signaling axis may be involved in the regulation of bone metabolism by Mage-D1.

Objective:To verify the feasibility and advantages of ARCHER-NM, a GPU-based fast Monte Carlo (MC) dose calculation engine, in calculating individualized doses of radiopharmaceutical therapy (RPT) through simulation experiments.Methods:The calculation reliability and efficiency of ARCHER-NM were verified by comparing its result with those of the MC software GATE in the water phantom experiments of radionuclide point sources and the dose calculations for RPT-treated patients. In the water phantom experiments, the generality of ARCHER-NM on different radionuclides was verified using common radionuclides like 67Cu, 89Sr, 90Y, 131I, 177Lu, and 188Re. The calculations of individualized doses for RPT-treated patients were tested based on the data of two patients from the University of Michigan′s public dataset for 177Lu-DOTATATE-treated cases. Gamma passing rates, dose volume histograms (DVHs), and average organ doses were employed to assess the consistency of ARCHER-NM and GATE in patients′ dose calculation result. The computing time was statistically analyzed to assess the efficiency of MC calculations. Results:In the water phantom experiments for all radionuclides, the relative differences of average doses between ARCHER-NM and GATE ranged from -1.63% to 2.29%, with an average absolute difference of 1.15%, suggesting high consistency. As indicated by the dose result of the two patients, the average doses for all organs between ARCHER-NM and GATE exhibited percentage errors of below 4%. The gamma passing rates for the two patients were 98.8% and 98.6%, respectively, under the 2 mm/1% standard within the 3% maximum dose isodose line. The simulation of 5 × 10 9decay required 90 s for ARCHER-NM on a personal host configured with a 24 GB Nvidia Titan RTX, whereas GATE took over 9 h on a 112-thread server for the same simulation. Conclusions:The water phantom experiments substantiate the accuracy and generality of ARCHER-NM for dose calculations. Based on the organ dose calculations of 177Lu-DOTATATE-treated patients, ARCHER-NM proves accurate and quick in calculating the individualized internal doses for RPT-treated patients. Therefore, ARCHER-NM plays a positive role in the dose planning of subsequent treatment and the protection of organs at risk including kidneys.

Objective: To establish reference values for carotid intima-media thickness (CIMT) of adult dwellers in Shenzhen City. Methods: The study was conducted based on the Shenzhen heart failure epidemiological survey from 2021 to 2022. In this survey, residents aged 18 years and above in Shenzhen were selected by using a multi-stage stratified random sampling method. General information, cardiovascular disease (CVD) related behavior and carotid ultrasound examination and etc. were collected from the participants. People with CVD factors, a history of atherosclerotic cardiovascular disease, carotid plaque or having no carotid ultrasound examination results were excluded. The parameter regression model based on fractional polynomial was used to establish the reference values of CIMT by age and sex. Results: A total of 2 163 healthy individuals were enrolled in the final analysis, including 576 males (26.6%) and 1 587 females (73.4%). The fractional polynomial regression of the CIMT mean and standard deviation was obtained. For men, the regression was mean_CIMT=0.324 7+0.006 9×age and SD_CIMT=0.076 9+0.001 2×age. For women, the regression was mean_CIMT=0.354 9+0.005 4×age and SD_CIMT=0.041 6+0.002 0×age. Conclusion: The age and sex reference values for CIMT of adult people in Shenzhen established in this study could provide the latest reference standards for early screening of subclinical CVD.
Male ; Humans ; Adult ; Female ; Carotid Intima-Media Thickness ; Cardiovascular Diseases ; Reference Values ; Carotid Arteries/diagnostic imaging* ; Ultrasonography, Carotid Arteries ; Risk Factors ; Carotid Artery Diseases

OBJECTIVE To explore the way to re-use epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKI） in patients with EGFR-TKI-induced interstitial pneumonia （IP）， using osimertinib as an example. METHODS The IP treatment regimen and re-use of EGFR-TKI regimen in a patient who developed IP after the use of osimertinib were analyzed. And a literature review was made by combining the characteristics of the cases which reported in the literature and the characteristics of this case. RESULTS The patient’s IP symptoms due to treatment with osimertinib had resolved after treatment. The patient’s IP symptoms also did not worsen after using almonertinib in combination with hormones as re-use of EGFR-TKI regimen. However， almonertinib was discontinued as the patient experienced disease progression. The adverse reactions of IP needed to be dealt with in time， the EGFR-TKI should be discontinued and symptomatic treatment should be given. CONCLUSIONS EGFR-TKI targeted therapy could be re-selected by replacing EGFR-TKI， adjusting the dose of EGFR-TKI， and using hormones in combination. EGFR-TKI-induced adverse drug reactions of IP are rare， but need to be observed closely. If other EGFR-TKI is used， close monitoring of adverse reactions and curative effects are also required in order to adjust the patient’s treatment plan in time.