The chronicity of infectious diseases is an important field in the collaborative research of traditional Chinese and Western medicine. The warm disease theory of pathogen invading nutrient and blood aspects in traditional Chinese medicine （TCM） takes the struggle between healthy Qi and pathogenic Qi and cementation of Yin as the core pathogenesis， providing a unique theoretical framework for explaining the common pathology of infectious chronic diseases. This theory originated from Yin-Yang interaction in the Internal Classic and was enriched with WU Youke's theory of intruding pathogen interacting and lingering in blood vessels and YE Tianshi's theory of long-term illness entering collaterals. Combining the theory with modern medical knowledge， our team has condensed the dynamic pathogenesis model of deficiency （nutrient and blood aspects） and excess （pathogen） interacting in the blood collaterals of Yin aspect， the core feature of which is the four-dimensional interactions of cause （pathogen characteristics）， location （three Yin locations of diseases）， nature （deficiency and excess）， and potential （transmission trend）. The common pathology of infectious chronic diseases is reflected in interactions. That is， the interactions between nutrient and blood deficiency （immune exhaustion and metabolic disorder） and pathogen excess （pathogen persistence and fibrous hyperplasia） in the liver collaterals （Jueyin）， kidney collaterals （Shaoyin）， lung collaterals （Taiyin） and other blood collaterals of Yin aspect form the pathological damage characterized by immune inflammatory response-continuous tissue damage with excessive repair. Taking the inheritance and innovative development of classics as the main line， this paper systematically discusses the scientific connotation of the theory of pathogen invading nutrient and blood aspects and the paths of inheritance and innovation and clarifies the original significance of this theory in the chronic development of infectious diseases. Furthermore， taking clinical diseases as an example， this paper reflects the guiding value of this classical theory in the modern diagnosis and treatment of infectious diseases with integrated traditional Chinese and Western medicine and the application potential of this theory in solving complex medical problems through the construction of the innovative paradigm of precise diagnosis and treatment with integrated traditional Chinese and Western medicine.

Hepatocellular carcinoma （HCC）， a malignancy with high mortality， exhibits poor survival rates and prognosis. The profound suppression of the tumor immune microenvironment （TIME） and the abnormal hyperactivity of metabolic reprogramming （MR） are the two primary factors driving HCC progression. Traditional Chinese medicine has demonstrated significant efficacy in HCC treatment. The team proposed that "deficiency of healthy Qi and stasis toxins" was the core pathogenesis of HCC， closely associated with TIME suppression and MR hyperactivity. This paper proposed that a suppressed state of the TIME was the biological manifestation of "deficiency of healthy Qi"， where the functional exhaustion of effector T lymphocytes and natural killer cells reflected the decline of "healthy Qi" in eliminating pathogens. Conversely， the expansion and activation of immunosuppressive cells， such as regulatory T cells （Tregs）， M2-like tumor-associated macrophages （TAM-M2）， and myeloid-derived suppressor cells （MDSCs） ， represent the dysfunction of "healthy Qi" in maintaining homeostasis. MR serves as the material basis of "stasis toxins". Stasis toxins exhibit heat stagnation， manifested by abnormal hyperactivity of glycolysis and lipid synthesis. They demonstrate migratory propensity， as toxic metabolites like lactic acid and prostaglandin E2 promote tumor invasion and metastasis. They display a consumptive nature， reflected in the functional suppression of immune cells. The vicious cycle between TIME and MR is the biopathological reflection of "deficiency of healthy Qi intertwined with stasis toxins". Immunosuppression exacerbates MR， while toxic metabolites further impair immune function， establishing a pathogenic chain of "deficiency leading to stasis， and stasis toxins damaging healthy Qi". The primary therapeutic approach is reinforcing healthy Qi， resolving stasis， and removing toxins， which can reinforce and tonify healthy Qi to regulate pathways， such as phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， C-X-C chemokine receptor type 4/ C-X-C chemokine ligand 12 （CXCR4/CXCL12）， and toll-like receptor 4/ nuclear factor-kappa B/ signal transducer and activator of transcription 3 （TLR4/NF-κB/STAT3）， adjust T lymphocyte ratios， inhibit Tregs/TAM-M2 function， and downregulate immune checkpoints， including programmed death ligand 1/programmed death 1（PD-L1/PD-1）， and reshape TIME. It is also involved in resolving stasis and removing toxins to modulate phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） and hypoxia-inducible factor-1α （HIF-1α） signaling pathways， suppress key enzymes in glycolysis and lipid synthesis， and block toxic metabolite production. Thus， this therapy synergistically regulates the immune and metabolic network， breaks the vicious cycle of "deficiency in healthy Qi and stasis toxins"， and offers a novel strategy for integrating traditional Chinese medicine and Western medicine in HCC treatment.

Purpose: Due to the preservation of the entire stomach after endoscopic resection, the occurrence of metachronous gastric cancer (MGC) remains a possibility. In this study, we investigated the incidence and risk factors for MGC in patients with early gastric cancer who underwent endoscopic submucosal dissection (ESD) and successfully eradicatedHelicobacter pylori. Materials and Methods: A retrospective analysis was conducted of 1,191 patients who underwent ESD and successfully eradicated H. pylori at the Affiliated Drum Tower Hospital of Nanjing University. Endoscopic surveillance was performed at 3, 6, and 12 months post-resection, and annually thereafter. MGC was defined as the development of a new cancer at a site other than the primary gastric cancer site, at least 1 year after the initial endoscopic resection. Results: A total of 77 patients were diagnosed with MGC during a median follow-up of 41.5 months. Kaplan-Meier analysis showed a 5-year cumulative incidence of MGC of 9.4% after successful H. pylori eradication. Multivariate analysis of the training set using Cox proportional hazards models identified male sex, severe atrophic gastritis, multiple gastric cancers before H. pylori eradication, and smoking history as independent risk factors for MGC.The nomogram exhibited favorable discrimination, with area under the curves of 0.767 and 0.822 in the training set and 0.724 and 0.745 in the testing set at 3 and 5 years, respectively. Conclusions Patients with gastric cancer who undergo endoscopic resection, even after successful H. pylori eradication, should undergo annual and continuous endoscopic surveillance for MGC.

ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

Circadian rhythm(CR)is an intrinsic biological clock mechanism within organisms that regulates physiological and biochemical processes, enabling synchronization with periodic fluctuations in the external environment. This rhythmicity not only influences the sleep-wake cycle but also encompasses various physiological functions, including metabolism, hormone secretion, cell proliferation, and immune responses. Age-related macular degeneration(ARMD), a prevalent retinal disease, has been significantly associated with disruptions in CR. ARMD is among the leading causes of vision loss in the elderly, with a complex pathogenesis involving multiple factors such as genetics, environmental influences, and lifestyle choices. This article will focus on the molecular mechanisms linking CR and ARMD, analyzing how disruptions in CR affect the physiological state and metabolic processes of retinal cells, ultimately contributing to the onset and progression of ARMD. Additionally, this article will elucidate the interactions effects of CR on ARMD in relation to oxidative stress, regulation of Aβ, inflammatory pathways, and mitochondrial homeostasis. By deepening our understanding of the relationship between CR and ARMD, we aim to provide new insights and directions for future clinical interventions and treatments.

Heart failure （HF） is the end stage of various cardiovascular diseases， manifested as ventricular filling or impaired left ventricular ejection fraction （LVEF）. Type 2 diabetes mellitus （T2DM） is a metabolic disorder， mainly caused by insufficient insulin secretion and insulin resistance. The incidence rates of the two common clinical diseases are increasing year by year. HF and T2DM are mutually causal chronic diseases， and their mutual deterioration can form a HF-T2DM comorbidity. The comorbidity status significantly increases the mortality and readmission risk of patients， and seriously affects the quality of life of patients. At present， western medicine treatment mainly involves the use of anti HF drugs and hypoglycemic drugs， which can significantly alleviate the clinical symptoms of patients. However， these two categories of drugs are numerous in variety and differ in their mechanisms， and blind combination may produce adverse reactions. With its unique theoretical system， traditional Chinese medicine exhibits the advantages of multiple components， multiple targets， and high safety through traditional Chinese medicine monomers， Chinese patent medicine， traditional Chinese medicine compounds， and acupuncture， which significantly delays the development of HF-T2DM and shows great potential in clinical treatment. A large number of clinical studies have shown that the integrated traditional Chinese and western medicine in the treatment of HF-T2DM has a significant effect in improving cardiac function， controlling blood glucose levels， and improving the quality of life of patients. Based on relevant research at home and abroad， this paper reviewed the HF-T2DM pathogenesis， pharmacological effects， research status of traditional Chinese and western medicine， and early prevention strategies， and discussed current problems and future research directions， in order to provide new ideas and useful references for clinical prevention and treatment of HF-T2DM.

Heart failure （HF） is the end stage of various cardiovascular diseases， manifested as ventricular filling or impaired left ventricular ejection fraction （LVEF）. Type 2 diabetes mellitus （T2DM） is a metabolic disorder， mainly caused by insufficient insulin secretion and insulin resistance. The incidence rates of the two common clinical diseases are increasing year by year. HF and T2DM are mutually causal chronic diseases， and their mutual deterioration can form a HF-T2DM comorbidity. The comorbidity status significantly increases the mortality and readmission risk of patients， and seriously affects the quality of life of patients. At present， western medicine treatment mainly involves the use of anti HF drugs and hypoglycemic drugs， which can significantly alleviate the clinical symptoms of patients. However， these two categories of drugs are numerous in variety and differ in their mechanisms， and blind combination may produce adverse reactions. With its unique theoretical system， traditional Chinese medicine exhibits the advantages of multiple components， multiple targets， and high safety through traditional Chinese medicine monomers， Chinese patent medicine， traditional Chinese medicine compounds， and acupuncture， which significantly delays the development of HF-T2DM and shows great potential in clinical treatment. A large number of clinical studies have shown that the integrated traditional Chinese and western medicine in the treatment of HF-T2DM has a significant effect in improving cardiac function， controlling blood glucose levels， and improving the quality of life of patients. Based on relevant research at home and abroad， this paper reviewed the HF-T2DM pathogenesis， pharmacological effects， research status of traditional Chinese and western medicine， and early prevention strategies， and discussed current problems and future research directions， in order to provide new ideas and useful references for clinical prevention and treatment of HF-T2DM.

Primary biliary cholangitis （PBC） is an autoimmune-mediated chronic cholestatic liver disease. Ursodeoxycholic acid （UDCA） is the first-line treatment drug for PBC， yet some patients with suboptimal biochemical response to UDCA face a significant increase in the risk of disease progression and often have a poor prognosis. This article systematically summarizes the currently established criteria for biochemical response and analyzes the factors and underlying mechanisms associated with suboptimal UDCA response from multiple perspectives including genetic background， demographic factors， immunological features， and the gut-liver axis. Furthermore， it outlines the available second-line treatment drugs and emerging therapies， in order to provide a basis for early identification of high-risk patients and optimization of treatment strategies， as well as a reference for future research directions.

Objective: To analyze the trajectories of cognitive function changes and their influencing factors among the elderly, so as to provide evidence for the prevention and intervention of cognitive impairment in this population. Methods: Data were obtained from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), which was conducted in 2011, 2014, and 2018. Information on demographic characteristics and lifestyle behaviors of elderly individuals aged ≥65 years was collected. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Group-based trajectory modeling was conducted using MMSE scores from 2011, 2014, and 2018 to identify trajectories of cognitive function change. The optimal trajectory model was determined using the Bayesian information criterion, Akaike information criterion, and average posterior probability. Factors affecting cognitive function trajectories among the elderly were analyzed using a Multinomial logistic regression model. Results: Data were collected from 2 614 individuals, with the mean age of (78.20±8.93) years. There were 1 251 males (47.86%) and 1 363 females (52.14%). The group-based trajectory model identified three distinct cognitive function trajectories, defined as the stable group, slow decline group, and rapid decline group, consisting of 2 187 (83.66%), 170 (6.50%), and 257 (9.83%) individuals, respectively. Multinomial logistic regression analysis showed that compared with the stable group, each 1-year increase in age was associated with a 315.7% higher risk of being classified into the slowly declining group (OR=4.157, 95%CI: 2.922-5.914) and a 214.6% higher risk of being classified into the rapidly declining group (OR=3.146, 95%CI: 2.428-4.076). Compared with elderly individuals with no formal education, those with primary/junior high school education had a 67.5% lower risk of being classified into the slowly declining group (OR=0.325, 95%CI: 0.207-0.511) and a 30.2% lower risk of being classified into the rapidly declining group (OR=0.698, 95%CI: 0.505-0.964). Compared with unmarried/divorced/widowed elderly individuals, those who were married had a 31.0% lower risk of being classified into the rapid decline group (OR=0.690, 95%CI: 0.509-0.935). Conclusions Based on the CLHLS data, cognitive function trajectories among individuals aged ≥65 years were classified into three patterns: stable, slow decline, and rapid decline. Increased age was associated with a higher risk of cognitive decline, while higher educational level and being married demonstrated protective effects against cognitive deterioration.

Objective:To establish a rapid and precise dose measurement method with EBT4 film and ensure its measurement accuracy to be within the required range through strict operational procedures for the purpose of addressing the two essential issues of poor measurement accuracy and timeliness of EBT film under FLASH conditions.Methods:After storing under different humidity conditions for a certain period of time, the film was exposed to radiation for analyzing the influence of air humidity on the intrinsic performance of EBT film. By means of repeated scanning operations and the film angle rotation, the influences of repeated scanning and film placement angle were analuzed. Parabolic correction method was used to reduce the spatial position influence during the scanning process. By analying the relationship between net optical density (netOD) and absorbed dose through the comparison of three fitting method, the optimal fitting curve was selected. After irradiation of the same batch of films for 5 min and 24 h, the film doses were calibrated and then compared with ionization chamber-measured result. The rapid and precise film dosimetry method was used to measure both the percentage depth dose from X-rays at ultra-high dose rate and the dose distribution at a depth of 2 cm in water.Results:Air humidity had the greatest influence on the intrinsic performance of EBT film (approximately 20%). The average deviation of repeated scans is within 0.5%. The angle at which the film is placed significantly affected the readouts of the film with the maximum influence approximately 70%. The net optical density combined with polynomial fitting can control the fitting residuals of 1-16 Gy within 3%. The change rate of light channels at 5 min already mostly met the requirements of the rapid mode (< 0.5%). Compared with the measurement result obtained using the reference ionization chamber, the deviations of the 5 min or 24 h dose calibration curves were all within 2%.Conclusions:The EBT4 film can be employed as a precise dosimeter to quickly measure the FLASH radiation dose. Rapid and precise FLASH dose measurements can meet the stringent requirements of both preclinical and clinical FLASH research.