ObjectiveTo explore the impact of exogenous chitosan on the growth and metabolism of Glycyrrhiza uralensis Fisch. (G. uralensis) and to improve the quality of cultivated G. uralensis for both medicine and food and aid in the increase in the content of effective components in G. uralensis.MethodsIn this study, whole G. uralensis plants were treated with exogenous chitosan, and comprehensive analyses of secondary metabolites and proteins were conducted using liquid chromatography with tandem mass spectrometry and isobaric tag for relative and absolute quantitation, respectively. Effects of chitosan induction on endogenous hormones of G. uralensis were analyzed using an enzyme-linked immunosorbent assay. Gene ontology function annotation and Kyoto Encyclopedia of Genes and Genomes pathway annotation were conducted to study the effect of chitosan induction on the proteome.ResultsChitosan induction significantly increased the levels of flavonoids in G. uralensis; however, the variation in triterpenoids was not substantial. Biological processes, including photosynthesis, secondary metabolism, and abiotic stress responses, were significantly enriched. Additionally, the photosynthetic pathway, photosynthesis-antenna protein pathway, and plant hormone signal transduction pathway were significantly enriched. In the flavonoid biosynthesis pathway, the upstream-related enzyme phenylalanine ammonia-lyase (PAL) and the downstream-related enzymes chalcone synthase (CHS), polyketide reductase (PKR), chalcone isomerase (CHI), and vestitone reductase (VR) were significantly upregulated.ConclusionsOur findings suggest that chitosan induction may promote the tricarboxylic acid (TCA) cycle, and the TCA cycle enhancement significantly upregulated PAL, CHS, PKR, CHI, and VR, the five key enzymes involved in flavonoid synthesis of G. uralensis, indicating that chitosan induction activated the entire metabolic pathway associated with flavonoids in G. uralensis. Our findings provide a reference for improving the quality of cultivated G. uralensis from the perspective of pharmacodynamic components.

Objective To investigate the contamination status of cloth mouse pads in dental clinics,and provide theoretical basis for standardizing environmental surface disinfection and scientific intervention in dental clinics.Methods The contamination status of cloth mouse pads in 5 dental clinics were investigated by adenosine triphos-phate(ATP)fluorescence detection method,visual observation method,and bacterial culture method.Disinfection efficacy of ultraviolet disinfection method and wiping disinfection using two types of disinfectant wipes on cloth mouse pads and photovoltaic glass mouse pads was compared.Intervention measures(using photovoltaic glass mouse pads,regular cleaning and disinfecting)were taken,and contamination status of cloth mouse pads in different departments before and after intervention was compared.Results The baseline investigation found that the conta-mination status of mouse pads varied in different dental clinics.The qualified rate of bacterial culture of mouse pads in department of endodontics was the lowest(20.00％),followed by the department of periodontology(30.00％).There was statistically significant difference in ATP detection values between two types of disinfectant wipes before and after wiping and disinfecting photovoltaic glass mouse pads(both P＜0.001).After using photovoltaic glass mouse pads,the contamination of mouse pads in 5 dental clinics was alleviated,and the qualified rate of ATP detec-tion increased(＞80％),compared with qualified rate of ATP detection before intervention,differences were all sta-tistically significant(all P＜0.001).Conclusion The contamination of the cloth mouse pads in dental clinics is seri-ous,and the conventional cloth mouse pad is difficult to be cleaned and disinfected.It is suggested that medical in-stitutions use the mouse pad which is convenient for cleaning and disinfection,and specify the disinfection method and frequency to control the contamination of the mouse pads.

Objective To investigate the contamination status of cloth mouse pads in dental clinics,and provide theoretical basis for standardizing environmental surface disinfection and scientific intervention in dental clinics.Methods The contamination status of cloth mouse pads in 5 dental clinics were investigated by adenosine triphos-phate(ATP)fluorescence detection method,visual observation method,and bacterial culture method.Disinfection efficacy of ultraviolet disinfection method and wiping disinfection using two types of disinfectant wipes on cloth mouse pads and photovoltaic glass mouse pads was compared.Intervention measures(using photovoltaic glass mouse pads,regular cleaning and disinfecting)were taken,and contamination status of cloth mouse pads in different departments before and after intervention was compared.Results The baseline investigation found that the conta-mination status of mouse pads varied in different dental clinics.The qualified rate of bacterial culture of mouse pads in department of endodontics was the lowest(20.00％),followed by the department of periodontology(30.00％).There was statistically significant difference in ATP detection values between two types of disinfectant wipes before and after wiping and disinfecting photovoltaic glass mouse pads(both P＜0.001).After using photovoltaic glass mouse pads,the contamination of mouse pads in 5 dental clinics was alleviated,and the qualified rate of ATP detec-tion increased(＞80％),compared with qualified rate of ATP detection before intervention,differences were all sta-tistically significant(all P＜0.001).Conclusion The contamination of the cloth mouse pads in dental clinics is seri-ous,and the conventional cloth mouse pad is difficult to be cleaned and disinfected.It is suggested that medical in-stitutions use the mouse pad which is convenient for cleaning and disinfection,and specify the disinfection method and frequency to control the contamination of the mouse pads.

Objective: To investigate the prevalence of frailty and its influencing factors among the elderly, so as to provide the evidence for prevention and control of frailty. Methods: The elderly population at ages of 65 years and older were selected from 14 administrative villages or communities in Wuzhong District, Suzhou City, Jiangsu Province, using the random cluster sample method from July to November, 2022. Demographic information, smoking and alcohol consumption were collected through questionnaire surveys. Physical activity, sleep quality and frailty were evaluated using the International Physical Activity Questionnaire-Short, Pittsburgh Sleep Quality Index and the FRAIL Scale, respectively. Factors affecting frailty among the elderly were evaluated using a multinomial logistic regression model. Results: A total of 8 782 elderly peolple were surveyed, including 4 259 males (48.50%) and 4 523 females (51.50%). The median age was 71.00 (interquartile range, 8.00) years. There were 2 145 cases with pre-frailty (24.42%) and 189 cases with frailty (2.15%). Multinomial logistic regression analysis showed that age (75-<85 years, OR=1.330, 95%CI: 1.186-1.492; ≥85 years, OR=2.452, 95%CI: 1.882-3.195), smoking (current smoking, OR=0.838, 95%CI: 0.714-0.983), physical activity level (low, OR=1.161, 95%CI: 1.010-1.333) and sleep quality (poor, OR=2.248, 95%CI: 1.822-2.774) were associated with pre-frailty; age (75-<85 years,OR=2.629, 95%CI: 1.921-3.596; ≥85 years, OR=3.067, 95%CI: 1.621-5.801), educational level (junior high school and above, OR=0.488, 95%CI: 0.298-0.798), body mass index (underweight, OR=1.848, 95%CI: 1.023-3.337; obesity, OR=1.798, 95%CI: 1.180-2.740), smoking (quit smoking, OR=1.787, 95%CI: 1.007-3.171; current smoking, OR=0.448, 95%CI: 0.242-0.830), alcohol consumption (yes, OR=0.532, 95%CI: 0.291-0.972), physical activity level (low, OR=2.757, 95%CI: 1.646-4.616) and sleep quality (poor, OR=3.911, 95%CI: 2.438-6.273) were associated with frailty. Conclusion Older, low physical activity level, poor sleep quality, underweight and obesity are associated with frailty of the elderly.

Objective:To explore the factors influencing electronically-delivered cognitive behavioral therapy for insomnia (e-CBTI) selection among patients with insomnia, and to provide empirical evidence for the clinical promotion of e-CBTI.Methods:Between November 2022 and July 2023, a convenience sampling method was employed to collect samples from 38 public hospitals and their surrounding communities. A total of 756 insomnia patients aged 18-65 years were included in the study. Based on their choice to participate in e-CBTI treatment, patients were divided into two groups: 605 patients (605/756,80.0%) chose to participate in e-CBTI treatment, while 151 patients (151/756,20.0%) did not. Rater-rated structured clinical interviews were applied in the current study, assessing individual′s insomnia symptoms, mental disorders, other sleep disorders, and suicidality and self-injury. The chi-square test and logistic regression were applied in data analyses.Results:Compared to the control group, the e-CBTI group had a higher proportion of females (χ 2=4.29) and a higher educational level (χ 2=5.76), while the proportion of living in rural areas was lower (χ 2=6.87), all with P<0.05. Additionally, the e-CBTI group exhibited a higher proportion of daytime symptoms compared to the control group, including decreased attention or memory (χ 2=16.42), impaired function or performance (χ 2=6.75), mood changes (χ 2=4.71), and reduced enthusiasm, energy, or motivation (χ 2=4.77), all with P<0.05. The e-CBTI group also showed a higher tendency for delayed sleep phase (χ 2=6.61), generalized anxiety disorder (χ 2=6.22), suicidal ideation (χ 2=10.45), and non-suicidal self-injury (χ 2=5.19), all with statistically significant differences ( P<0.05). Multivariate logistic regression analysis revealed that the type of residence ( OR=0.53, 95 %CI=0.29-0.95), educational level ( OR=2.42, 95 %CI=1.34-4.37), decreased attention or memory ( OR=1.95, 95 %CI=1.11-3.42), impaired function or performance ( OR=1.80, 95 %CI=1.15-2.82), and suicidal ideation ( OR=3.12, 95 %CI=1.29-7.58) remained significant influential factors in the selection of e-CBTI. Insomnia′s nighttime symptoms, including difficulty falling asleep, difficulty maintaining sleep, and early morning awakenings, were not associated with the inclination to choose e-CBTI. Conclusions:Daytime symptoms of insomnia and suicidal ideation are significant factors that prompt insomnia patients to choose e-CBTI.

Objective:To explore the factors influencing electronically-delivered cognitive behavioral therapy for insomnia (e-CBTI) selection among patients with insomnia, and to provide empirical evidence for the clinical promotion of e-CBTI.Methods:Between November 2022 and July 2023, a convenience sampling method was employed to collect samples from 38 public hospitals and their surrounding communities. A total of 756 insomnia patients aged 18-65 years were included in the study. Based on their choice to participate in e-CBTI treatment, patients were divided into two groups: 605 patients (605/756,80.0%) chose to participate in e-CBTI treatment, while 151 patients (151/756,20.0%) did not. Rater-rated structured clinical interviews were applied in the current study, assessing individual′s insomnia symptoms, mental disorders, other sleep disorders, and suicidality and self-injury. The chi-square test and logistic regression were applied in data analyses.Results:Compared to the control group, the e-CBTI group had a higher proportion of females (χ 2=4.29) and a higher educational level (χ 2=5.76), while the proportion of living in rural areas was lower (χ 2=6.87), all with P<0.05. Additionally, the e-CBTI group exhibited a higher proportion of daytime symptoms compared to the control group, including decreased attention or memory (χ 2=16.42), impaired function or performance (χ 2=6.75), mood changes (χ 2=4.71), and reduced enthusiasm, energy, or motivation (χ 2=4.77), all with P<0.05. The e-CBTI group also showed a higher tendency for delayed sleep phase (χ 2=6.61), generalized anxiety disorder (χ 2=6.22), suicidal ideation (χ 2=10.45), and non-suicidal self-injury (χ 2=5.19), all with statistically significant differences ( P<0.05). Multivariate logistic regression analysis revealed that the type of residence ( OR=0.53, 95 %CI=0.29-0.95), educational level ( OR=2.42, 95 %CI=1.34-4.37), decreased attention or memory ( OR=1.95, 95 %CI=1.11-3.42), impaired function or performance ( OR=1.80, 95 %CI=1.15-2.82), and suicidal ideation ( OR=3.12, 95 %CI=1.29-7.58) remained significant influential factors in the selection of e-CBTI. Insomnia′s nighttime symptoms, including difficulty falling asleep, difficulty maintaining sleep, and early morning awakenings, were not associated with the inclination to choose e-CBTI. Conclusions:Daytime symptoms of insomnia and suicidal ideation are significant factors that prompt insomnia patients to choose e-CBTI.

OBJECTIVE To establish a method for concentration determination of caffeine and its three metabolites， theophylline， paraxanthine and theobromine in urine， and apply it in clinical practice. METHODS Using caffeine-13C3-d3 as internal standard （IS）， and the urine samples were protein precipitated with acetonitrile； HPLC-MS/MS method was adopted to determine the concentrations of caffeine and its three metabolites. The determination was performed on Waters ACQUITY UPLC® BEH HILIC column with mobile phase consisting of 60 mmol/L ammonium acetate （A）-acetonitrile （B） （gradient elution） at the flow rate of 0.5 mL/min. The column temperature was set at 38 ℃ ， and the sample size was 2 μL. The electrospray ionization detection was operated in a positive mode by multiple reaction monitoring. The detection ions for quantitative analysis were m/z 195.1→110.0 for caffeine， m/z 181.1→124.0 for theophylline， m/z 181.1→124.0 for paraxanthine， m/z 181.1→138.0 for theobromine， and m/z 198.1→ 140.1 for IS. The above method was used to determine the concentrations of caffeine and its three metabolites in the urine of 19 infants with apnea of prematurity （AOP）. RESULTS The linear ranges of mass concentration of caffeine， theophylline， paraxanthin and theobromine were 0.200-200， 0.050-50.0，0.050 0-50.0， and 0.100-100 μg/mL， respectively. The lower limits of quantification were 0.200， 0.050， 0.050 and 0.100 μg/mL （r＞0.990）， respectively. RSDs of intra-day and intra- day precision were not above 10.37%， and matrix factors were 85.68%-109.90%； extraction recoveries were 93.53%-109.40% （RSD≤15%）， and RSDs of stability tests were all lower than 15%. The concentrations of caffeine and its three metabolites in the urine of 19 cases were （27.346±7.951）， （0.351±0.223）， （0.428±0.395） and （0.472±0.374） μg/mL， respectively. CONCLUSIONS The established HPLC-MS/MS method is simple， sensitive and can be used for the determination of caffeine and its three metabolites in urine samples of AOP.

Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC_50s for BD and BC were 11.63 and 11.71 μmol·L^-1, respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD's role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.
Humans ; Lung Neoplasms/metabolism* ; STAT3 Transcription Factor/metabolism* ; Antineoplastic Agents/chemistry* ; A549 Cells ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation

Criteria for diagnosis of Alzheimer's disease (AD) is not available in China.The international criteria is not a proper choice due to issues such as translation and lead to low diagnostic rate and high rate of missed diagnosis.The research group of Alzheimer's Disease Chinese (ADC) reviewed knowledge and techniques in neuropsychology,neuroimaging,molecular biology,and clinical neurology,and systematically studied the detection techniques such as memory,language,visuospatial,executive function,and medial temporal lobe visual scores on MRI,and their optimal threshold and diagnostic value for the diagnosis of AD.Through a systematic review and consensus meeting,a diagnostic framework for screeningAD in the Chinese population was established.Among these methods,an operational standard for clinical pathology models increased the diagnostic sensitivity by 15％.The sensitivity and specificity of screening memory impairment increased by 18.1％ and 11.6％,respectively.The sensitivity of screening medialtemporal lobe atrophy increased by 24.5％ and missed diagnosis was decreased by 34.5％.An operational standard for clinical biology models,incorporating the latest molecular imaging and molecular biology techniques,has enabled the early diagnosis of AD in China.The framework combines a principled diagnostic guideline with an operational screening protocol,which is applicable to all clinical settings and of great significance for the early detection,early diagnosis and early treatment of AD.

Objective: To investigate the short-term efficacy and toxicity of bevacizumab combined with DP or rh-endostatin（recombinant human vascular endostatin injection）combined with DP in locally advanced EGFR wild-type non-small cell lung cancer (NSCLC). Methods: Seventy-two patients with treatment of locally advanced EGFR wild-type NSCLC admitted to the Department of Respiratory Medicine of Zhongshan Hospital Affiliated to Guangdong Medical University from January 2014 to January 2017 were divided into bevacizumab group (34 cases) and rh-endostatin group (38 cases) according to the random number method. The former group was treated with bevacizumab combined with docetaxel and cisplatin, while the latter was treated with rh-endostatin combined with docetaxel and cisplatin. According to RECISIT 1.1 standard, the changes of lesion size before and after treatment in two groups were evaluated. Serum levels of vascular endothelial growth factor (VEGF), carcinoembryonic antigen (CEA), cytokeratin 21-1 fragment (CYFRA21-1), squamous cell carcinoma antigen (SCC) were measured. The adverse reactions during treatment were also evaluated. Results: In bevacizumab group, patients with CR, PR, SD, PD, DCR and ORR were 2 cases, 12 cases, 15 cases, 5 cases, 41.18% and 85.29%, respectively. In rh-endostatin group, patients with CR, PR, SD, PD, DCR, ORR were 2 cases, 16 cases, 14 cases, 6 cases, 47.37% and 84.21%, respectively. The DCR in rh-endostatin group was significantly higher than that in bevacizumab group (P<0.05).The serum levels of VEGF and CEAin rh-endostatin group decreased more obvious than those in bevacizumab group (all P<0.05). The incidence of gastrointestinal reaction, skin reaction and cardiac toxicity in rh-endostatin group was higher than that in bevacizumab group, while the incidence of bleeding in bevacizumab group was higher than that in rh-endostatin group (all P<0.05). Conclusion: In patients with locally advanced EGFR wild-type NSCLC, rh-endostatin combined with DP regimen is better than bevacizumab combined with DPregimen. In clinical practice, corresponding treatment regimen can be selected according to different characteristics of patients, so as to minimize the toxic reaction during treatment and avoid clinical risk.