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.

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.

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.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective To explore the perioperative trend of heart rate variability(HRV)in patients undergoing aortic valve replacement(AVR)under cardiopulmonary bypass and investigate the influence of age and/or postoperative atrial fibrillation(POAF)on this trend.Methods Baseline and clinical data of 134 patients undergoing AVR due to aortic valve disease in Department of Car-diovascular Surgery of Northern Theater General Hospital of PLA from January 2021 to January 2023 were collected and retrospectively studied.According to the age and/or POAF,they were divided into group A(aged＜60 years,no POAF,49 cases),group B(aged＜60 years,complicated with POAF,21 cases),group C(aged≥60 years,no POAF,30 cases)and group D(aged≥60 years,with POAF,34 cases).The dynamic electrocardiogram indicators were collected in 7 d be-fore and 7 d after operation.The changes in perioperative HRV were also observed.Results After operation,the standard deviation of sinus heart beat RR intervals,average of the standard devia-tions of NN intervals for each 5 min segment of a 24 h HRV recording(SDNNidx),root mean square of successive RR interval differences,and percentage of successive RR intervals that differ by more than 50 ms were significantly lower than those in 7 d before operation[61.172±17.449 ms vs 804.567±230.518 ms,20.284±9.432 ms vs 42.933±12.876 ms,1.307±0.196 ms vs 1.412±0.148 ms,3.00(1.30,7.23)ms vs 5.30(3.00,10.40)ms,P＜0.01].The group D had obvi-ously lower SDNNidx than the group A in 7 d after surgery(42.568±14.749 ms vs 46.467±11.754 ms,P＜0.05).Conclusion Autonomic dysfunction is observed in the early stage after AVR.For the patients aged≥60 years with POAF,the HRV indicators are significantly decreased,the dys-function of the vagus nerve is aggravated,and the disorder is exacerbated because of their syner-gistic effect.

Objective To investigate the short-term efficacy of the retrograde semi-retrieval technique(RESET)in the treatment of patients with acute intracranial large vessel occlusion.Methods This retrospective study involved 286 patients with acute intracranial large vessel occlusion who underwent mechanical thrombectomy using RESET at Tianjin Huanhu Hospital from November 2017 to March 2019.The patients were divided into two groups based on the presence or absence of intracranial atherosclerotic stenosis(ICAS):ICAS group(n=186,65％)and non-ICAS group(n=100,35％).Baseline characteristics,procedural outcomes,and 90-day modified Rankin Scale(mRS)scores were compared between the two groups.Results The two groups did not significantly differ in baseline characteristics,including age,gender,past medical history,on-admission National Institutes of Health Stroke Scale(NIHSS)score,and Alberta Stroke Program Early CT(ASPECT)score(all P＞0.05).Successful vascular recanalization was achieved in 272 patients(95.1％),with 209 patients(73.1％)achieving complete recanalization with a single thrombectomy attempt.Rescue therapy was required in 33 patients(11.5％).Two patients in the ICAS group died due to postoperative symptomatic intracranial hemorrhage,and one patient in the non-ICAS group died due to postoperative multiple organ failure.Compared with the non-ICAS group,the ICAS group had a significantly longer puncture-to-recanalization time[141.36(124.11,156.53)min vs.65.17(53.92,83.25)min,P＜0.001]but a significantly smaller number of thrombectomy attempts[1.00(1.00,1.00)vs.1.00(1.00,2.00),P=0.002].However,there were no significant differences between the two groups in terms of final recanalization rate,complete recanalization rate with a single thrombectomy attempt,distal embolism or embolization of new territory,symptomatic intracranial hemorrhage,perioperative death,or 90-day mRS score(all P＞0.05).Conclusion RESET demonstrates satisfactory short-term efficacy in the treatment of acute intracranial large vessel occlusion.The number of thrombectomy attempts required for complete recanalization is significantly lower in the ICAS group than in the non-ICAS group,suggesting that RESET is particularly suitable for patients with ICAS.

Objective In this study,we aimed to predict the inhibitory mechanism of Shenlingcao oral liquid(SLC)in non-small cell lung cancer(NSCLC)by network pharmacology and verify it by molecular docking and in vivo experiments.Methods The active ingredients and corresponding targets of SLC and NSCLC were obtained by database and literature search.Targets of SLC common to NSCLC were selected to construct the protein interaction network,and GO and KEGG enrichment analysis and molecular docking were performed.A Lewis lung cancer mouse model was constructed and divided into Model group,SH group,and SL group.The latter two groups were intragastrically administered 8.75 g SLC lyophilized powder/kg and 3.50 g SLC lyophilized powder/kg,respectively.After 14 days of drug intervention,tumor growth,pathological changes in tumor tissue,and apoptosis in tumor tissue were observed in tumor-bearing mice;changes in blood routine indexes and the tumor tissue expression of p-AKT,AKT,p-PI3K,PI3K,and Bcl-2 protein of mice were detected.The result of the KEGG enrichment analysis were verified.Results Network pharmacological analysis showed that there were 77 active ingredients,618 potential targets,1498 potential targets for NSCLC,and 179 drug and disease intersection targets.Target intersection enrichment analysis showed that they were mainly concentrated in the phosphatidylinositol 3 kinase-protein kinase B(PI3K-AKT)signaling pathway,mitogen-activated protein kinase(MAPK)signaling pathway,and other related pathways.Molecular docking showed that the top 10 core components had good bonding ability with the top 10 core targets.In the animal experiments,compared with the Model group,SH group and SL group had significantly decreased tumor volume and weight(P＜0.05,P＜0.01),and significantly decreased white blood cell,neutrophil,and monocyte numbers(P＜0.01,P＜0.001).Red blood cells,platelets,and hemoglobin were significantly increased(P＜0.05,P＜0.01,P＜0.001);apoptotic cells were significantly increased in early tumor tissue(P＜0.05,P＜0.01),and the protein expression levels of p-PI3K/PI3K,p-AKT/AKT,and Bcl-2/GAPDH were significantly decreased(P＜0.05,P＜0.01).The expression levels of PI3K,AKT1,and Bcl-2 genes were significantly decreased(P＜0.05,P＜0.01).Conclusions The mechanisms of SLC activity against NSCLC may be related to the activation of the PI3K-AKT pathway and the promotion of apoptosis.

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.