ObjectiveTo explore the effect of timosaponin BⅡ （TBⅡ） combined with icariin （ICA） on osteoclast （OC）-osteoblast （OB） coupling and decipher the mechanism from the cellular level. MethodsThe cell counting kit-8 （CCK-8） was used to assess the effects of different concentrations of TBⅡ and different concentrations of TBⅡ+ICA on the growth of RAW264.7 cells. Soluble receptor activator of nuclear factor-κB ligand （sRANKL） was used to induce the differentiation of RAW264.7 pre-osteoclasts into osteoclasts. The cells were allocated into sRANKL， TBⅡ （1， 5， 10 μmol·L^-1）， and TBⅡ+ICA groups. Tartrate-resistant acid phosphatase staining was performed to assess the effects of TBⅡ and TBⅡ+ICA on osteoclast differentiation. Real-time quantitative polymerase chain reaction （Real-time PCR） was conducted to examine the effects of TBⅡ+ICA on the expression of key genes involved in osteoclast differentiation and osteoclast-derived coupling factors. The osteogenic differentiation conditioned medium mixed with osteoclast supernatant was used to induce osteogenic differentiation of MC3T3-E1 cells. Alkaline phosphatase staining and alizarin red S staining were employed to determine the effect of TBⅡ+ICA on osteogenic differentiation. Real-time PCR was employed to evaluate the effects of conditioned medium on key genes involved in osteogenic differentiation. ResultsTBⅡ at 1， 5， 10 μmol·L^-1 had no significant effect on the cell survival rate. Compared with the sRANKL group， TBⅡ inhibited osteoclast differentiation in a dose-dependent manner and achieved the best effect at 10 μmol·L^-1 （P<0.01）. Compared with the sRANKL group， different concentrations of TBⅡ down-regulated the mRNA levels of osteoclast differentiation-related genes c-Fos， RANK， and RANKL （P<0.05）. None of 10 μmol·L^-1 TBⅡ， 10 μmol·L^-1 TBⅡ+10^-4 μmol·L^-1 ICA， or 10 μmol·L^-1 TBⅡ+10^-3 μmol·L^-1 ICA affected the viability of RAW264.7 cells. TBⅡ and/or ICA inhibited osteoclast differentiation （P<0.01）， and TBⅡ + ICA had the best effect （P<0.01）. Compared with the sRANKL group， TBⅡ and/or ICA down-regulated the mRNA levels of c-Fos， RANK， and RANKL （P<0.05）. The single application of TBⅡ and ICA had no significant effect on the mRNA levels of Wnt10b， Cthrc1， and C3a， while TBⅡ+ICA exerted up-regulating effects （P<0.05）. Compared with those in the blank group， the bone differentiation and mineralization abilities of the normal osteogenic induction group and each osteogenic induction + osteoclast supernatant group were improved （P<0.01）. Compared with the blank group， the normal osteogenic induction group and the osteogenic induction + osteoclast supernatant group showed up-regulated mRNA levels of Runx2 and OCN （P<0.01）. ConclusionTBⅡ+ICA can inhibit osteoclast differentiation， maintain the normal osteoclast-osteoblast coupling， and promote osteogenic differentiation.

Objective To evaluate the accuracy of bioelectrical impedance analysis(BIA)in measurement of appendicular skeletal muscle mass(ASM)of adults.Methods A total of 836 adults aged 18-42 years were recruited in Guangzhou using a convenient sampling method from April 2021 to September 2022.ASM was measured using BIA and Dual-energy X-ray absorptiometry(DXA).Using DXA as the standard method,the consistency between the BIA and DXA measurements was evaluated by intra-class correlation coefficients(ICCs)and Bland-Altman analysis in logarithmically transformed data,in order to evaluate the accuracy of BIA in ASM measurement.Receiver operating characteristic curve was plotted to evaluate the diagnostic value of BIA for screening low muscle mass.Results A total of 774 individuals were included for analysis finally.ICCs for ASM measured by BIA and DXA were 0.774 and 0.667 in males and females,respectively.Mean ratios(limits of Agreement)of ASM were 0.94(0.80-1.10)and 0.91(0.78-1.05)in males and females,respectively.Area under curve of BIA for screening low muscle mass were 0.91 and 0.94 in males and females,respectively.The optimal cut-off values of Z-score by BIA for males and females were-0.57 and-0.66,respectively.Sensitivity and specificity for males were 82.5%and 86.0%,while being 86.8%and 93.8%,for females.Conclusion BIA shows a moderate consistency with DXA for measuring ASM in adults.Furthermore,BIA yields a good diagnostic value in identifying low muscle mass in adults aged 18-42 years.

Objective To investigate the influence of type 2 diabetes mellitus(T2DM)on cognitive function and the effective connectivity with in the default mode network(DMN)in the brain.Methods A total of 93 hospitalized patients diagnosed with T2DM were enrolled in this study as T2DM group from The First Affiliated Hospital of Guangzhou University of Chinese Medicine during September 2021 to December 2022.Simultaneously,108 healthy individuals were recruited from the community as normal control(NC)group.The cognitive functions were evaluated in the two groups.A random dynamic causal modeling approach was employed to analyze the effective connectivity within DMN in both groups.Additionally,Pearson correlation analysis was performed to examine the association between differential connectivity,clinical indicators,and cognitive scores in both groups.Results In comparison to the NC group,T2DM individuals exhibited statistically significant reductions in scores in the auditory verbal learning test(AVLT)for immediate recall and the digit symbol substitution test(DSST)(P＜0.05).Additionally,they displayed a notable decrease in effective connectivity from the left lateral parietal cortex(LLPC)to the posterior cingulate cortex(PCC),as well as from the LLPC to the right lateral parietal cortex(RLPC)within the DMN(P＜0.05).Pearson correlation analysis unveiled a negative association between HbA1c levels and the strength of effective connectivity from LLPC to PCC.Conversely,a positive correlation was observed between AVLT(immediate)scores and the strength of effective connectivity from LLPC to PCC and LLPC to RLPC.Additionally,DSST scores displayed a positive correlation with the strength of effective connectivity from LLPC to PCC(P＜0.05).Conclusion Patients with T2DM display compromised effective connectivity from LLPC to PCC and LLPC to RLPC within the DMN network,and this alteration may associated with cognitive impairment.

Recent progress in targeted metabolic therapy of cancer has been limited by the considerable toxicity associated with such drugs. To address this challenge, we developed a smart theranostic prodrug system that combines a fluorophore and an anticancer drug, specifically 6-diazo-5-oxo-l-norleucine (DON), using a thioketal linkage (TK). This system enables imaging, chemotherapy, photodynamic therapy, and on-demand drug release upon radiation exposure. The optimized prodrug, DON-TK-BM3, incorporating cyanine dyes as the fluorophore, displayed potent reactive oxygen species release and efficient tumor cell killing. Unlike the parent drug DON, DON-TK-BM3 exhibited no toxicity toward normal cells. Moreover, DON-TK-BM3 demonstrated high tumor accumulation and reduced side effects, including gastrointestinal toxicity, in mice. This study provides a practical strategy for designing prodrugs of metabolic inhibitors with significant toxicity stemming from their lack of tissue selectivity.

Interferon regulatory factor 1(IRF-1)is a member of the IRF family.It is the first transcription factor to be identified that could bind to the interferon-stimulated response element(ISRE)on the target gene and displays crucial roles in the interferon-induced signals and pathways.IRF-1,as an important medium,has all of the advantages of full cell cycle regulation,cell death signaling transduction,and reinforcing immune surveillance,which are well documented.Current studies indicate that IRF-1 is of vital importance to the occurrence and evolution of multifarious liver diseases,including but not limited to inhibiting the replication of the hepatitis virus(A/B/C/E),alleviating the progression of liver fibrosis,and aggravating hepatic ischemia-reperfusion injury(HIRI).The tumor suppression of IRF-1 is related to the clinical characteristics of liver cancer patients,which makes it a potential indicator for predicting the prognosis and recurrence of liver cancer;additionally,the latest studies have revealed other effects of IRF-1 such as protection against alcoholic/non-alcoholic fatty liver disease(AFLD/NAFLD),cholangiocarcinoma suppression,and uncommon traits in other liver diseases that had previously received little attention.Intriguingly,several compounds and drugs have featured a protective function in specific liver disease models in which there is significant involvement of the IRF-1 signal.In this paper,we hope to propose a prospective research basis upon which to help decipher translational medicine applications of IRF-1 in liver disease treatment.

Alexithymia is a multidimensional personality trait characterized by the difficulties to identify self-feelings and describe feelings and extroverted thinking.Alexithymia is considered a potential feature of paroxysmal mi-graine,chronic migraine,and medication overuse headache.At present,there are few studies on the association between migraine and alexithymia,and by reviewing the concept,classification,risk factors,and mechanisms of alexithymia and the association between alexithymia and migraine,this article explores the characteristics of alexithymia in migraine pa-tients,in order to improve the ability to identify alexithymia among clinicians during the diagnosis and treatment of head-ache,thereby helping patients to receive timely intervention and treatment.

Antimicrobial resistance (AMR), is regarded as one of the top 10 global public health threats. Addressing AMR through the One Health strategy has become a global consensus. AMR monitoring plays a crucial role as the cornerstone of AMR response strategies. This study thoroughly analyzed current situation and progress of AMR monitoring based on the One Health concept in China, the United Kingdom, the United States, and the European Union, and comprehensively compared the similarities and differences of AMR monitoring systems across these countries and regions. The research found that cross-national, cross-regional, and cross-sectoral cooperation in AMR monitoring is increasingly strengthening. However, notable discrepancies still exist among different countries and regions. Notably, most AMR monitoring systems prioritize human and animal health, with relatively insufficient monitoring in the environmental sector. Given the current landscape, China still needs to continue to promote standardized AMR monitoring data sharing and integration across the human, animal, food, and environmental fields, striving to construct a comprehensive and systematic "whole-chain" AMR monitoring system to better tackle this global public health challenge effectively.

Objective: To investigate the factors influencing parents willingness to vaccinate their children against influenza in Guangzhou, and to provide a scientific basic for effectively improving the coverage rate of influenza vaccine in children. Methods: According to economic level, one secondary school and one elementary school in each of the central administrative and peripheral districts of Guangzhou were selected by stratified cluster sampling. A questionnaire survey was conducted among 5 133 parents of the school students. Questionnaire content included the basic characteristics of children and their parents, and parents knowledge of influenza vaccination for children. Results: A total of 14.57%(748/5 133) of parents were unwilling to have their children vaccinated against influenza. The results of the multivariate Logistic regression analysis found that, compared with parents aged ≤35 years old, parents aged 41-45 years and ≥46 years were 49% (adjusted OR=1.49, 95%CI =1.11-2.00) and 86% (adjusted OR= 1.86 , 95%CI =1.33-2.60), respectively, more likely to refuse vaccinating their children. Parents with an annual income ≥ 200 000 yuan were 52% more likely to be unwilling to vaccinate their children than those with annual income <100 000 yuan (adjusted OR=1.52, 95%CI =1.12-2.06). Parents living within a walking distance ≥30 minutes from the vaccination clinic were 52% more likely to be vaccinereluctant than those living within a walking distance of ≤10 minutes (adjusted OR=1.52, 95%CI = 1.16- 1.99). Compared with parents who regarded the vaccine as safe, parents who did not believe that it was safe or who were unsure of its safety were more likely to refuse vaccinating their children, with adjusted OR(95%CI ) of 12.75(9.44-17.23) and 3.37(2.73- 4.15 ), respectively( P <0.01). Conclusion Parents age, annual income, recognition of the safety of influenza vaccines, and walking distance to the vaccination clinic are associated with parents willingness to vaccinate children against influenza. Hospitals, communities and schools should cooperate to carry out vaccination and popular science propaganda, and arrange vaccination sites rationally to improve the coverage of influenza vaccines.

Objective:To systematically summarize and assess risk prediction models for occurrence of cervical cancer and to provide evidence for selecting the most reliable model for practice, and guide cervical cancer screening.Methods:Two groups of keywords related to cervical cancer and risk prediction model were searched on Chinese databases (CNKI, and Wanfang) and English databases (PubMed, Embase, and Cochrane Library). Original articles that developed or validated risk prediction models and published before November 21, 2019, were selected. Information form was created based on the CHARMS checklist. The PROBAST was used to assess the risk of bias.Results:12 eligible articles were identified, describing 15 prediction models, of which five were established in China. The predicted outcomes included multiple stages from cervical precancerous lesions to cancer occurrence, i.e., abnormal Pap smear (1), occurrence or recurrence of CIN (9), and occurrence of cervical cancer (5), etc. The most frequently used predictors were HPV infection (12), age (7), smoking (5), and education (5). There were two models using machine learning to develop models. In terms of model performance, the discrimination ranged from 0.53 to 0.87, while only two models assessed the calibration correctly. Only two models were externally validated in Taiwan of China, using people in different periods. All of the models were at high risk of bias, especially in the analysis domain. The problems were concentrated in the improper handling of missing data (13), preliminary evaluation of model performance (13), improper use of internal validation (12), and insufficient sample size (11). In addition, the problems of inconsistency measurements of predictors and outcomes (8) and the flawed report of the use of blindness for outcome measures (8) were also severe. Compared with the other models, the Rothberg (2018) model had relatively high quality. Conclusions:There are a certain number of cervical cancer risk prediction models, but the quality is poor. It is urgent to improve the measurement of predictors and outcomes, the statistical analysis details such as handling missing data and evaluation of model performance and externally validate existing models to better guide screening.

Objective To investigate the levels of trace elements in preschool children in Guangzhou and their relationships with nutritional status, and to provide a scientific basis for guiding children's nutritional diet and timely and reasonable supplementation of trace elements. Methods A cross-sectional study was used to perform physical examinations and collect blood samples from 5 002 children who were examined in the Department of Pediatric Health of a Maternal and Child Health Hospital in Guangzhou in 2018. The levels of trace elements including iron, zinc and copper were detected by atomic absorption spectrometer. Results The median (upper and lower quartile) levels of iron, zinc and copper for preschool children in a district of Guangzhou were 7.80 (7.39, 8.19) mmol / L, 69.0 (61.0, 76.5) μmol / L, 18.6 (15.9, 21.4) μmol / L. There was no significant difference in the levels of iron, zinc and copper between different genders (P>0.05). The levels of iron and zinc increased significantly with the age of children (P=0.000). There was no significant difference in the level of copper in different ages (P>0.05). The prevalence rates of iron, zinc and copper deficiency in preschool children were 14.93%, 21.93% and 0.24%, respectively, and there was no significant difference between different genders (P>0.05).There were no significant differences in the prevalence of iron and copper deficiency in different ages (P>0.05), while the zinc deficiency rate decreased with the age of children (P = 0.000). (P<0.05). The levels of iron and zinc in overweight children, and those suffering from malnutrition,and obesity were lower than those in normal children. There was no statistically significant difference in the levels of copper in children with different nutritional status (P>0.05). The prevalence rates of iron and zinc deficiency in children with malnutrition, overweight and obesity were higher than those in normal children. There was no significant difference in the prevalence of copper deficiency in children with different nutritional status (P>0.05). Conclusion The prevalence of iron, zinc deficiency is high in preschool children in Guangzhou. Preschool children with malnutrition, overweight and obesity are more prone to iron and zinc deficiency.