Objective:To study the effect of different doses of 60Co γ-ray ionizing radiation on mitochondrial function in mouse hematopoietic stem and progenitor cells (HSPCs). Methods:C57BL/6 mice were divided into control group, 1 Gy irradiation group and 4.5 Gy irradiation group. The mitochondrial functions were detected at 12 h and 24 h after irradiation, including ROS level, membrane potential, mitochondrial structure, and mitochondrial stress. Bone marrow c-Kit + cells received a single 15 Gy irradiation in vitro, after 24 h, mitochondrial function was detected. Results:It was found that mice leukocytes ( t=12.41, 18.31, 16.48, 14.16, 19.08, 20.25, P<0.05), red blood cells ( t=4.81, 6.62, P<0.05) and platelets ( t=4.33, 6.68, P<0.05) were significantly reduced. The numbers of bone marrow colony formation unit ( t=16.27, 55.66, 17.06, 43.75, P<0.05), and HSPCs ( t=5.16, 11.55, P<0.05) were decreased dose-dependently post-irradiation. Under 1 Gy irradiation, the mitochondrial function and mitochondrial basal metabolic index of HSPCs ( t= 7.36, 3.68, 4.58, 3.15, 3.15, P<0.05) were enhanced at 24 h post-irradiation. Under 4.5 Gy irradiation, mitochondrial number, mitochondrial membrane potential ( t=12.29, 10.46, P<0.05), maximal respiration and spare respiratory capacity were decreased ( t=7.81, 5.78, 6.70, 5.83, P<0.05), ROS level was increased ( t=4.63, 4.12, P<0.05). The basal respiration and oxidative phosphorylated ATP production were reduced at 12 h after irradiation ( t=8.48, 3.80, P<0.05); and the proton leakage was increased ( t=6.57, P<0.05) and coupling efficiency was reduced ( t=11.43, P<0.05) at 24 h after irradiation. In cultured c-Kit + cells, the level of ROS ( t=11.30, P<0.05) and the maximum respiration and spare respiratory capacity were increased ( t=4.25, 3.44, P<0.05) while the mitochondrial membrane potential was decreased ( t=34.92, P<0.05) significantly. Conclusions:A method for systematically assessing mitochondrial function in HSPCs was established, and the effect of ionizing radiation on mitochondrial function of HSPCs was clarified, laying a foundation for further revealing the mechanism of ionizing radiation-induced mitochondrial damage in HSPCs.

Objective:To investigate the impact of serum vitamin A levels on all-cause mortality risk in diabetes patients.Methods:Diabetes patients aged 20 years and above who participated in the US National Health and Nutrition Examination Survey during 2003-2004 and 2005-2006 were enrolled as the study population,with death data up to 2019 as the endpoint.Cox proportional hazards regression models were employed to calculate the hazard ratios of all-cause mortality in diabetes patients with different serum vitamin A levels,both unadjusted and adjusted for confounders.Restricted cubic spline methods were used to analyze the dose-response relationship between serum vitamin A levels and all-cause mortality risk in diabetes patients.Results:A total of 484 diabetes patients were included,with a median follow-up period of 13.7 years,during which 211 deaths occurred.Cox proportional hazards analysis showed that compared to the lowest quartile of serum vitamin A,higher quartiles of serum vitamin A were not associated with all-cause mortality risk in diabetes patients without adjusting for confounders.However,after adjusting for confounders,higher quartiles of serum vitamin A significantly reduced the all-cause mortality risk.The dose-response analysis indicated a significantly increased risk of all-cause mortality in diabetes patients with lower serum vitamin A levels.As the vitamin A levels increased,the mortality risk gradually decreased.A significant reduction in all-cause mortality risk was observed when serum vitamin A levels were between 2.17 and 2.50 μmol/L.Beyond this range,there was a tendency for increased all-cause mortality risk with further increases in vitamin A levels.Conclusion:Lower serum vitamin A levels increase the all-cause mortality risk in diabetes patients,while moderate serum vitamin A levels help reduce the all-cause mortality risk in diabetes patients.

Lung cancer is the most common malignant tumor of the respiratory system， and its pathogenesis is still not fully understood. Despite the significant clinical efficacy achieved through treatments such as surgery， radiotherapy， chemotherapy， targeted therapy， and immunotherapy， they still come with many complications and significant adverse reactions. In recent years， numerous basic and clinical studies have confirmed the effectiveness of Chinese medicine in treating lung cancer. Chinese medicine features synergistic regulation through its multiple components， targets， pathways， and approaches. Active monomeric constituents in Chinese medicine are diverse， and their mechanisms of action are intricate， making it challenging to fully understand the mechanisms by which Chinese medicine prevents and treats lung cancer. Therefore， there is an urgent need to approach Chinese medicine intervention in lung cancer from a modern medical perspective， exploring the mechanisms of Chinese medicine intervention in lung cancer at the molecular biology and network pharmacology levels. According to traditional Chinese medicine （TCM）， the occurrence of lung cancer is predominantly attributed to factors such as deficiency of healthy Qi， presence of pathogenic factors， internal accumulation of heat-toxins， internal accumulation of phlegm-dampness， and Qi stagnation and blood stasis. Literature analysis reveals that Chinese medicine compound formulas for lung cancer predominantly include tonifying agents and heat-clearing and toxin-removing agents， such as Shashen Maidongtang， Xiaoyan prescription， and Feijinsheng prescription. The single herbs used mainly include heat-clearing， deficiency-tonifying， blood-activating， stasis-resolving， phlegm-resolving， cough-relieving， and asthma-calming categories. The use of Chinese medicine aligns with the TCM understanding of the etiology and pathogenesis of lung cancer. Studies have shown that TCM can regulate the expression of key molecules in lung cancer-related signaling pathways， such as the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， nuclear factor-kappa B （NF-κB）， Wnt/β-catenin， mitogen-activated protein kinase （MAPK）， and Janus kinase/signal transducer and activator of transcription （JAK/STAT）， thereby exerting effects such as reducing lung cancer cell activity， blocking the cell cycle， inhibiting proliferation and invasion of lung cancer cells， inducing apoptosis in lung cancer cells， promoting cell autophagy， and reversing drug resistance， and intervening in the progression of lung cancer. This study systematically summarized recent research progress on how Chinese medicine monomers or formulas regulated the aforementioned signaling pathways and key protein expression to exert anti-lung cancer effects， aiming to elucidate the mechanisms by which Chinese medicine intervenes in the progression of lung cancer and provide insights and theoretical basis for further research and clinical application of Chinese medicine in lung cancer intervention.

AIM: Describe the general situation of the First-In-Human trials of the drugs, and summarize the design and results of the First-In-Human trials. METHODS: We searched the literature of the First-In-Human trials in 2009-2020 on PubMed and screened out the literature that met the research purpose. The basic information of the literature was collected. Data analysis was conducted to summarize relevant outcomes. RESULTS: A total of 559 First-In-Human trials were included in this study. The types of drugs included small molecule drugs (52.42%, 293/559), macromolecule drugs (45.62%, 255/559), and a small amount of cells and viruses (1.97%, 11/559) and so on. Regarding the determination of the starting dose, whether it was in macromolecules (23.86%, 21/88) or small molecules (30.15%, 41/136), No Observed Adverse Effect Level (27.68%, 62/224) was mainly used as the main reference basis, followed by preclinical research (21.88%, 49/224) and Minimal Anticipated Biological Effect Level (8.48%, 19/224), etc. In the dose escalation test, 50.19%(135/269) of the studies used the traditional standard 3+3 dose escalation method, followed by the accelerated titration method (7.06%, 19/269), and the improved 3+3 method (6.69%, 18/269), etc. CONCLUSION: The design of First-In-Human clinical trials has certain regularity in the content and results of the research design. In the subsequent trials, it is important to scientifically design the First-In-Human trials, and promote the safe and effective development of the First-In-Human trials of the drugs.

ObjectiveTo investigate the identification of kidney Yang deficiency syndrome of patients with osteoporosis（OP）， and to form the clinical syndrome identification rules of traditional Chinese medicine（TCM）. MethodBasic information， etiology， clinical symptoms and other characteristics of 982 OP patients were included， and statistical tests were used to screen the variables associated with kidney Yang deficiency syndrome. Taking the decision tree as the base model， bootstrap aggregation algorithm（Bagging algorithm） was utilized to establish the classification model of kidney Yang deficiency syndrome in OP， generating numerous rules and removing redundancy. Combining least absolute shrinkage and selection operator（LASSO） regression to screen key rules and integrate them to construct an identification model， achieving the identification of kidney Yang deficiency syndrome in OP patients. ResultEighteen key identification rules were screened out， and of these， where 11 rules with regression coefficients>0 correlated positively with the kidney Yang deficiency syndrome， the rule with the highest coefficient was chilliness（present）&feverish sensation over the palm and sole（absent）. The other 7 rules with regression coefficients<0 correlated negatively with the syndrome， the rule with the lowest coefficient was reddish tongue（present）&diarrhea（absent）&deficiency of endowment（absent）. According to the regression coefficients of each key rule， variables with importance>0.2 were ranked as chilliness， reddish tongue， feverish sensation over the palm and sole， cold limbs， clear urine， diarrhea， deficiency of endowment， prolonged illness. The results of the partial dependence analysis of the identification model showed that compared to OP patients without chilliness， those with chilliness（present） had a 0.266 8 higher probability of being identified as having kidney Yang deficiency syndrome， indicating that this variable had the highest impact on identification of the syndrome. Similarly， compared to OP patients without reddish tongue， those with reddish tongue had a 0.141 9 lower probability of being identified as having kidney Yang deficiency syndrome， indicating that this variable had the highest impact on identifying non-kidney Yang deficiency syndrome. The accuracy， sensitivity， specificity and area under receiver operating characteristic curve（AUC） of the established kidney Yang deficiency syndrome identification model in the test set were 0.865 9， 0.853 7， 0.872 0 and 0.931 5， respectively. ConclusionA precise identification model of OP kidney Yang deficiency syndrome is conducted basing on the rule ensemble method of Bagging combining LASSO regression， and the screened key rules can explain the identification process of kidney Yang deficiency syndrome. In this research， according to the regression coefficients of rules， the importance and partial dependence of variables， combined with the thinking of TCM， the influence of patient characteristics on the identification of syndromes is described， so as to reveal the primary and secondary syndromes of identification and assist the clinical identification of kidney Yang deficiency syndrome.

This study used the Appraisal of Guidelines Research & Evaluation-Health Systems （AGREE-HS） to demonstratively compare 34 global coronavirus disease-2019 （COVID-19） health systems guidance documents （HSGs） and 6 World Health Organization （WHO） standard HSGs. The comparison involved topic， participants， methods， recommendations， and implementability， with the aim of exploring the characteristics of emergency HSGs. The results showed that the emergency HSGs had an overall average score of 49%， with topic having the highest score， recommendations having the second highest score， and participants having the lowest score. The standard HSGs had an overall average score of 79%， with high scores in all items. The emergency HSGs had lower scores in participants， methods， recommendations， and implementability than the standard HSGs （P<0.001）， while the COVID-19 emergency HSGs developed by the WHO had higher score in topic than the standard HSGs （P<0.05）. Compared with those released by countries， the COVID-19 emergency HSG developed by the WHO showed superiority in all items and overall scores （P=0.000 2）. This indicates that emergency HSGs， represented by the COVID-19 emergency HSG， place equal emphasis on topic and recommendations as standard HSGs but have low requirements in terms of expert participation， evidence support， and comprehensive consideration in the time- and resource-limited context. They have the characteristics of prominent topics， clear purposes， orientation to demand， keeping up with the latest evidence， flexible adjustment， and timeliness， emphasizing immediate implementation effects， weakening long-term effects， and focusing on comprehensive benefits. Additionally， developers， types， and report completeness are important influencing factors.