OBJECTIVE To explore the correlation between drug consumption index and diagnosis related groups （DRG） overspending cases， and provide a basis for hospitals to optimize the cost structure and strengthen the refined management. METHODS Based on the data of DRG patients enrolled in a third-grade class A hospital from September to November 2023， the multivariate Logistic regression model and restricted cubic spline （RCS） model were used to analyze the correlation of drug consumption index with DRG overspending cases and its threshold effect， respectively. At the same time， rational drug use evaluation was conducted based on the drug consumption index， precise cost control and management were carried out， and the changes in the main pharmaceutical indicators of the whole hospital were analyzed before control （January-June 2023） and after control （January-June 2024）. RESULTS The results of multivariate Logistic regression analysis showed that long hospitalization days， high drug consumption index， transfer to other departments and combined diabetes mellitus were the risk factors for DRG overspending （P＜0.05）. The results of the RCS model showed that the drug consumption index had a non-linear relationship with DRG overspending. When the drug consumption index was ≥0.64， the drug consumption index was positively correlated with the risk of DRG overspending（P＜0.05）. Compared with the same period before the control， medical cost per time， drug cost per time and drug consumption index decreased significantly after the control （P＜0.01）. CONCLUSIONS The drug consumption index is a risk factor for DRG overruns， there is a non-linear relationship and threshold effect between it and DRG overruns. Each hospital can set a reasonable threshold and implement dynamic monitoring and intervention by comprehensively considering the actual drug usage， disease spectrum characteristics， and cost control targets， as well as factors such as medical quality， patient needs， and the payment capacity of medical insurance， which can effectively achieve precise control over drug usage.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes. "Internal heat leading to zheng" is the core pathogenesis of DKD, while "glucose toxicity" is transformed from subtle substances through "internal heat" and the cementation of various pathological products, which is pivotal to the transformation of diabetes to DKD. "Glucose toxicity" is characterized by deep and widespread heat, caused by various pathological factors, and its sticky nature makes it difficult to resolve, which can cause severe damage to the kidney collaterals. In the early stage of "glucose toxicity", it is yang pathogen, which can be transformed into yin pathogen in the later stage with disease progression. In clinical practice, treatment should be based on disease staging, with attention on grasping the pathogenesis of "internal heat leading to zheng" and identifying the nature of "glucose toxicity". During the diabetic period, clearing heat is the primary method, often using modified Yueju Pill and Dachaihu Decoction. In the early stage of DKD, treatment primarily focuses on clearing and penetrating latent heat to treat DKD, aiming to prevent toxic heat from transitioning from qi to blood. The approach emphasizes clearing heat and re-penetrating, detoxification, and re-clearing, often using a self-made modified Qingre Xiaozheng Decoction. In the middle and late stages of DKD, the focus shifts to clearing heat, eliminating zheng, strengthening vital qi, and dispelling turbidity, with commonly used treatments including the self-made modified Xiezhuo Xiaozheng Formula, Jingui Shenqi Pill, and Zhenwu Decoction.

ObjectiveTo investigate the effect of Danggui Shaoyaosan on ferroptosis in the rat model of non-alcoholic fatty liver disease （NAFLD） and explore the underlying mechanism based on the nuclear factor E₂-related factor 2 （Nrf2）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） signaling pathway. MethodsThe sixty SD rats were randomly grouped as follows： control， model， Yishanfu （0.144 g·kg^-1）， and low-， medium-， and high-dose （2.44， 4.88， and 9.76 g·kg^-1， respectively） Danggui Shaoyaosan. A high-fat diet was used to establish the rat model of NAFLD. After 12 weeks of modeling， rats were treated with corresponding agents for 4 weeks. Then， the body weight and liver weight were measured， and the liver index was calculated. At the same time， serum and liver samples were collected. The levels or activities of total cholesterol （TC）， triglycerides （TG）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Fe²⁺ in the serum and TC， TG， free fatty acids （FFA）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione peroxidase （GPX）， and Fe²⁺ in the liver were measured. Hematoxylin-eosin staining and oil red O staining were employed to observe the pathological changes in the liver. Immunofluorescence was used to assess the reactive oxygen species （ROS） content in the liver. Mitochondrial morphology was observed by transmission electron microscopy. The protein levels of Nrf2， SLC7A11， GPX4， transferrin receptor 1 （TFR1）， and divalent metal transporter 1 （DMT1） in the liver were determined by Western blot. ResultsCompared with the control group， the model group showed increases in the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， and decreases in the activities of SOD， GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.05， P<0.01）. Meanwhile， the liver tissue in the model group presented steatosis， iron deposition， mitochondrial shrinkage， and blurred or swollen mitochondrial cristae. Compared with the model group， all doses of Danggui Shaoyaosan reduced the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， while increasing the activities of SOD and GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.01）. Furthermore， Danggui Shaoyaosan alleviated steatosis， iron deposition， and mitochondrial damage in the liver. ConclusionDanggui Shaoyaosan may inhibit lipid peroxidation and ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway to treat NAFLD.

With the rapid advancement of artificial intelligence technology, chatbots have shown great potential in the healthcare sector. From personalized health advice to chronic disease management and psychological support, chatbots have demonstrated significant advantages in improving the efficiency and quality of healthcare services. As the scope of their applications expands, the relationship between technological complexity and practical application scenarios has become increasingly intertwined, necessitating a more comprehensive evaluation of both aspects. This paper, from the perspective of he althcare applications, systematically reviews the technological pathways and development of chatbots in the medical field, providing an in-depth analysis of their performance across various medical scenarios. It thoroughly examines the advantages and limitations of chatbots, aiming to offer theoretical support for future research and propose feasible recommendations for the broader adoption of chatbot technologies in healthcare.

The vasculature plays a critical role in homeostasis and health as well as in the development and progression of a wide range of diseases, including cancer, cardiovascular diseases, metabolic diseases (and their complications), chronic inflammatory diseases, ophthalmic diseases, and neurodegenerative diseases. As such, the growth of the vasculature mediates normal development and physiology, as well as disease, when pathologically induced vessels are morphologically and functionally altered owing to an imbalance of angiogenesis-stimulating and angiogenesis-inhibiting factors. This review offers an overview of the angiogenic process and discusses recent findings that provide additional interesting nuances to this process, including the roles of intussusception and angiovasculogenesis, which may hold promise for future therapeutic interventions. In addition, we review the methodology, including those of in vitro and in vivo assays, which has helped build the vast amount of knowledge on angiogenesis available today and identify important remaining knowledge gaps that should be bridged through future research.
Animals ; Signal Transduction/physiology* ; Humans ; Neovascularization, Pathologic/physiopathology* ; Neovascularization, Physiologic/physiology* ; Models, Animal ; Angiogenesis

OBJECTIVES: To investigate the impact of incorrect specification of the working correlation structure matrix on estimated sample size in a 2×2 crossover design based on the generalized estimating equation (GEE). METHODS: Based on Monte Carlo simulation, the influence of incorrect specification of the work-related structure matrix on the sample size estimation under different conditions was evaluated after controlling the total sample size n, the proportion of subjects assigned to AB sequence (s=1) θ, the correlation coefficient ρ, and the placebo effect OR. Bias and mean square error (MSE) were used to assess the difference between the sample size estimates and the theoretical values. RESULTS: When the correctly specified working correlation structure matrix is independent, the sample size estimation effect of correctly specifying the working correlation structure matrix is better than that of incorrect specification. But when the correctly specified working correlation structure matrix is equal and the correlation coefficient is closer to 0, with other factors being smaller (n≤50, θ≤0.5, OR=2 in this article), there is a situation where the bias of the sample size estimation value for the correctly specified working correlation structure matrix is greater than the bias for the incorrectly specified working correlation structure matrix. CONCLUSIONS Under most conditions, incorrectly specifying the working correlation structure matrix can cause the estimated sample size to deviate significantly from the theoretical value, but under certain conditions, the impact of incorrectly specifying the working correlation structure matrix can be small on the estimated sample size.
Sample Size ; Monte Carlo Method ; Humans ; Cross-Over Studies ; Computer Simulation ; Research Design ; Bias

ObjectiveTo investigate the regulatory effect of Danggui Shaoyaosan on adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR）/Unc-51-like kinase-1 （ULK1） signaling pathway in the rat model of metabolism-associated fatty liver disease （MAFLD）. MethodSixty SD rats were randomized into control， model， western medicine （polyene phosphatidylcholine capsules，0.144 g·kg^-1）， and low-， medium-， and high-dose （2.44， 4.88， 9.76 g·kg^-1， respectively） Danggui Shaoyaosan groups. After being fed with a high-fat diet for 8 weeks， the rats in each group were administrated with corresponding drugs for 4 weeks. At the end of drug treatment， serum and liver tissue were collected for subsequent determination of related indicators. ResultCompared with the control group， the model group showed increased contents of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C） and activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in the serum， increased contents of TC， TG， and free fatty acids （FFAs） in the liver （P<0.01）， and decreased content of high-density lipoprotein cholesterol （HDL-C） in the serum （P<0.01）. Furthermore， the model group showed down-regulated protein levels of p-AMPK， microtubule-associated protein 1 light chain 3B （LC3B） Ⅱ， Beclin1， and ULK1 （P<0.01） and up-regulated protein levels of p-mTOR and ubiquitin-binding protein p62 in the liver （P<0.01）. The hepatic steatosis was obvious and the NAFLD activity score （NAS） and oil red O staining area increased in the model group， （P<0.05， P<0.01）. Compared with the model group， Danggui Shaoyaosan reduced the contents of TC and TG and the activities of ALT and AST in the serum， lowered the levels of TC， TG， and FFA in the liver， down-regulated the protein levels of p-mTOR and p62 （P<0.01）， elevated the serum HDL-C level， and up-regulated the protein levels of p-AMPK， LCBⅡ， Beclin1， and ULK1 in the liver （P<0.05， P<0.01）. Moreover， it alleviated hepatic steatosis and decreased the NAS and oil red O staining area （P<0.05， P<0.01）. ConclusionDanggui Shaoyaosan has therapeutic effect on MAFLD rats by regulating AMPK/mTOR/ULK1 signaling pathway to enhance autophagy.

As a supplement to randomized controlled trials， observational studies can provide evidence for the effectiveness of traditional Chinese medicine （TCM） treatment measures. They can also study influencing factors of diseases， etiology， and prognosis. However， there is a confounding effect due to the lack of randomization， which seriously affects the causal inference between the study factors and the outcome， resulting in confounding bias. Therefore， identifying and controlling confounding factors are key issues to be addressed in TCM observational studies. According to the causal network and the characteristics of TCM theory， confounding factors can be categorized into measured and unmeasured confounding factors. In addition， attention must be paid to identifying confounding factors and intermediate variables， as well as the interaction between confounding factors and study factors. For methods of controlling confounding factors， measured confounding factors can be controlled by stratification， multifactor analysis， propensity scores， and disease risk scores. Unmeasured and unknown confounding factors can be corrected using instrumental variable methods， difference-in-difference methods， and correction for underlying event rate ratios. Correcting and controlling confounding factors can ensure a balance between groups， and confounding bias can be reduced. In addition， methods such as sensitivity analysis and determination of interactions make the control of confounding factors more comprehensive. Due to the unique characteristics of TCM， observational studies of TCM face unique challenges in identifying and controlling confounding factors， including the ever-changing TCM treatment measures received by patients， the often-overlooked confounding effects in the four diagnostic information of TCM， and the lack of objective criteria for TCM evidence-based diagnosis. Some scholars have already conducted innovative explorations to address these issues， providing a methodological basis for conducting higher-quality TCM observational studies， so as to obtain more rigorous real-world evidence of TCM and gradually develop quality evaluation criteria for OS that are consistent with the characteristics of TCM.

WANG Qishi put forward the theory of "yang deficiency with three lackings， controlled by the spleen" in Lixu Yuanjian （《理虚元鉴》）， which regarded that yang deficiency can lead to consumptive diseases with changes of lacking essence， lacking qi， and lacking fire， so the treatment should start from the spleen to restore the middle yang urgently. This article summarised the experience of treating type 4 cardiorenal syndrome based on the theory of "yang deficiency with three lackings， controlled by the spleen"， and proposed that lacking essence is the beginning of the onset of type 4 cardiorenal syndrome， lacking qi is the gradual development of the disease， and lacking fire is the changes of the disease， and ultimately resulted in the complex situation of kidney and qi deficiency， and edema due to yang deficiency， combined with syndromes variation. In the clinical evidence， in the stage of lacking fire， therapies should warm the middle and strengthen the spleen in order to rescue the middle yang， prescribed with modified Baoyuan Decoction （保元汤） plus Lizhong Decoction （理中汤）； in the stage of lacking qi， prescriptions can add Taoren （Juglans regia）， Tubiechong （Eupolyphaga sinensis）， Fuling （Smilax glabra）， Guizhi （Neolitsea cassia） to activate blood and drain water to transport and restore the center qi； in the stage of lacking essence， prescriptions can add Gouqizi （Lycium barbarum）， Tusizi （Cuscuta chinensis）， Duzhong （Eucommia ulmoides）， Bajitian （Gynochthodes officinalis） to supplement deficiency and resolve masses to consolidate the root and supplement essence.