Diabetic retinopathy（DR）， as one of the most common and serious microvascular complications of diabetes mellitus， seriously threatens human health， and belongs to "Xiaoke eye diseases" in traditional Chinese medicine（TCM）， which has been richly experienced by medical practitioners through the ages， but is mostly recorded in a piecemeal manner and has not been systematically researched. This disease is featured by long course and repeated attack， and is refractory， which belongs to the research category of "persistent illness entering collaterals". Systematic establishment of TCM collateral disease theory for guiding prevention and treatment of DR has important clinical value. On the basis of close correlation between tertiary collaterals at the terminal of collaterals and capillaries and microcirculation， the concept of "tertiary collaterals-microvascular" is proposed. It is pointed out that DR falls within the scope of "tertiary collaterals-microvascular" diseases， and presents four types of micro-pathological characteristics， including stasis， insufficiency， growth and bleeding of tertiary collaterals. It is concluded that "deficiency of both Qi and Yin" is the basic pathogenesis of DR， and "blood stasis and collateral obstruction" is the important pathogenesis and key factor. Thus， the treatment method of "dispersing blood stasis， dredging collateral， tonifying Qi and Yin， stopping hemorrhage and improving eyesight" is determined， and the formula of Tongluo Mingmu capsules is developed. The article tightly focuses on the pathological changes such as stasis， growth， insufficiency and bleeding of collaterals， addresses both symptoms and root causes， and plays a synergistic role of both dispersing stasis and stopping bleeding. In this way， it can realize the purpose of tonifying Qi and Yin to replenish the essence， dispersing stasis and dredging collaterals to meet the requirement， as well as stopping hemorrhage and improving eyesight to deal with changes. Fundamental researches demonstrate that Tongluo Mingmu capsules has synergy effects of protecting both retinal capillaries and retinal cells. Phase-Ⅲ clinical trial of new drug has proven definite clinical efficacy and good safety， which provides a new drug choice for enhancing clinical effect of DR， and further supports the scientific value of Luobing theory in preventing and treating DR and other clinically significant diseases.

In the Qing Dynasty， YE Gui proposed the pathogenesis of "chronic diseases entering the collaterals" as a rule for collateral diseases. In the context of viral respiratory diseases， the course of the disease is considered a relative concept. A systematic review of historical literature reveals that "new pathogens" belong to the category of "new diseases". It identifies that "new diseases" include types where the pathogenic qi initially invades without harming the righteous qi， where old diseases relapse while not being completely cured， and where chronic diseases suddenly flare up. These are not limited to exogenous diseases. "New pathogens" refer to diseases caused by the invasion of warm-heat pathogens， the six excesses， and epidemic qi， differing from the modern traditional Chinese medicine term "new warm diseases" related to latent heat diseases. Based on the "collaterals-meridians-collaterals" transformation pathway described in The Inner Canon of Yellow Emperor （《黄帝内经》） and the pathogenesis of external pathogens entering the zang-fu organs via the meridians as described in Treatise on Febrile Disease （《伤寒论》）， as well as the external warm diseases' transformation rule explained by YE Gui from the perspective of collaterals， the concept of "new pathogen invading the collaterals" is proposed. Further analysis indicates that this concept aligns with the transmission and pathogenesis patterns of viral respiratory diseases. The treatment method of "clearing epidemic pathogens， detoxifying， and spreading the lung to relieve heat" is considered important for the prevention and control of viral respiratory infectious diseases.

ObjectiveExploring the formula rules of commonly used traditional Chinese medicines（TCMs） for epidemic treatment from the Qin and Han dynasties to the Qing dynasty through data mining， providing reference for the prevention and control of contemporary epidemics. MethodsThe articles on epidemic treatment in the electronic database of Chinese Medical Code V5.0 were systematically searched， and the contents such as source， dynasty， author， diagnosis， formula name， therapeutic method and efficacy， and composition of medicines from each article that met the inclusion criteria were extracted. Then， an Excel standardized database was established， and Python programs were used for data mining to summarize the frequency of commonly used medicines and perform hierarchical cluster analysis， Pearson correlation analysis， and association rule analysis. ResultsA total of 1 595 formulas were included， involving 558 TCMs. The efficacy of these medicines could be classified into two categories， namely， expeling pathogenic factors and reinforcing healthy Qi. According to the frequency deconstruction analysis， high-frequency medicines were mainly detoxification， Fu-organ dredging， aromatization and promoting blood circulation， followed by the medicines with the effect of treating the lungs， such as clearing the lungs and resolving phlegm， clearing heat and purging the lungs， relieving cough and asthma， and purging the lungs and relieving asthma. And the proportions of acrid-warm herbs and acrid-cold herbs varied in different periods. Hierarchical clustering and correlation analysis both suggested TCMs for expeling pathogenic factors and reinforcing healthy Qi often formed stable combinations with high association degrees. Association rule analysis showed that the core acrid-warm herb was mainly Ephedrae Herba， and the core acrid-cold herb was mainly Forsythiae Fructus， resulting in the core formulas of Maxing Shigantang and Yinqiaosan. ConclusionThroughout history， the prevention and control of epidemics have been based on the principle of "preserving healthy Qi and avoiding toxic Qi"， focusing on the treatment of the causes and characteristics of epidemics through detoxification， Fu-organ dredging， and aromatization， emphasizing the use of Rhei Radix et Rhizoma and other herbs to dredge Fu-organ， eliminate toxins and pathogens， and playing the role of actively intervene with symptomatic medication. And based on the external manifestations of the body's struggle between evil and righteousness， diagnose and treatment according to syndrome differentiation was performed.

ObjectiveExploring the formula rules of commonly used traditional Chinese medicines（TCMs） for epidemic treatment from the Qin and Han dynasties to the Qing dynasty through data mining， providing reference for the prevention and control of contemporary epidemics. MethodsThe articles on epidemic treatment in the electronic database of Chinese Medical Code V5.0 were systematically searched， and the contents such as source， dynasty， author， diagnosis， formula name， therapeutic method and efficacy， and composition of medicines from each article that met the inclusion criteria were extracted. Then， an Excel standardized database was established， and Python programs were used for data mining to summarize the frequency of commonly used medicines and perform hierarchical cluster analysis， Pearson correlation analysis， and association rule analysis. ResultsA total of 1 595 formulas were included， involving 558 TCMs. The efficacy of these medicines could be classified into two categories， namely， expeling pathogenic factors and reinforcing healthy Qi. According to the frequency deconstruction analysis， high-frequency medicines were mainly detoxification， Fu-organ dredging， aromatization and promoting blood circulation， followed by the medicines with the effect of treating the lungs， such as clearing the lungs and resolving phlegm， clearing heat and purging the lungs， relieving cough and asthma， and purging the lungs and relieving asthma. And the proportions of acrid-warm herbs and acrid-cold herbs varied in different periods. Hierarchical clustering and correlation analysis both suggested TCMs for expeling pathogenic factors and reinforcing healthy Qi often formed stable combinations with high association degrees. Association rule analysis showed that the core acrid-warm herb was mainly Ephedrae Herba， and the core acrid-cold herb was mainly Forsythiae Fructus， resulting in the core formulas of Maxing Shigantang and Yinqiaosan. ConclusionThroughout history， the prevention and control of epidemics have been based on the principle of "preserving healthy Qi and avoiding toxic Qi"， focusing on the treatment of the causes and characteristics of epidemics through detoxification， Fu-organ dredging， and aromatization， emphasizing the use of Rhei Radix et Rhizoma and other herbs to dredge Fu-organ， eliminate toxins and pathogens， and playing the role of actively intervene with symptomatic medication. And based on the external manifestations of the body's struggle between evil and righteousness， diagnose and treatment according to syndrome differentiation was performed.

Objective:To investigate the efficacy and adverse reactions of whole-lung low-dose radiotherapy (LDRT) in patients with severe/critical coronavirus disease 2019 (COVID-19).Methods:Eight patients with severe/critical COVID-19 treated in the Jiangyin Hospital Affiliated to Nantong University from January to June 2023 who were treated with whole-lung LDRT after deteriorating or failing to improve post-medical treatment were enrolled in this single-arm phase I clinical trial. They received anterior-posterior penetrating radiation in a supine or prone position, with a total dose range from 0.5 to 1.5 Gy and a dose weight ratio of 1∶1. The oxygenation status, inflammatory markers, and imaging changes before and after radiotherapy were analyzed, and patients were followed up for acute radiation-induced adverse reactions.Results:One week after LDRT, the SaO 2/FiO 2 or PaO 2/FiO 2 indices increased in seven patients (87.5%), inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) decreased in seven patients (87.5%), and chest CT/chest radiographs revealed a significant reduction in the extent of pneumonia involvement in 5 patients (62.5%). No evident acute radiation-related adverse reactions were observed. Conclusions:Whole-lung LDRT with a dose range from 0.5 to 1.5 Gy can reduce inflammatory markers, improve clinical symptoms, and promote inflammatory absorption in patients with severe/critical COVID-19 who responded poorly to medical treatment while not inducing acute adverse reactions.

Objective To investigate the efficacy of hypofractionated radiotherapy (HFRT) combined with programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors in sequential with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) for the treatment of advanced metastatic solid tumors. Methods A prospective single-center single-arm study was designed for patients failed standard treatments for advanced refractory solid tumors in the Department of Radiotherapy of Jiangyin Hospital affiliated to Nantong University, and eligible patients were given quadruple therapy: HFRT (5 to 8 Gy × 2 to 3 f) once every 21 days for at least 2 cycles; 200 μg GM-CSF from the 1st to 7th day of radiotherapy, and 2 million IU IL-2 from the 8thto 14th day. Within 1 week after the completion of HFRT, PD-1/PD-L1 inhibitors were used for treatment. The above treatment strategy was repeated. GM-CSF and IL-2 were treated for 6 cycles, followed by maintenance with PD-1/PD-L1 inhibitors until disease progression (PD) or intolerable toxicity occurred. Objective response rate (ORR) and treatment-related adverse events were analyzed. Results From January 9, 2021 to June 15, 2023, totally 40 patients were enrolled, with follow-up of 2.8 to 31.0 months and a median follow-up of 9.9 months, and 39 patients (97.5%) completed at least one time tumorsite evaluation within the non-radiotherapy target area. 97.5% of patients had cancers, 2.5% had soft tissue sarcomas, and 20.0% had received immune checkpoint inhibitors (ICIs) at baseline check. The ORR was 30.8%, and the disease control rate (DCR) was 71.8%; the ORR for non-small cell lung cancer (NSCLC) was 28.6%, and the DCR was 57.1%; the ORR for colorectal cancer was 14.3%, and the DCR was 71.4%; the ORR for gastric cancer was 16.7%, and the DCR was 66.7%; 28 patients (70.0%) had treatment-related adverse events (TRAE), 4 patients (10%) had TRAE≥level 3, and the most common types of TRAE were fatigue, fever and hypothyroidism. Conclusion The treatment of HFRT combined with immune checkpoint inhibitors in sequential with GM-CSF and IL-2 is well tolerated and toxicity accepted in patients with advanced metastatic solid tumors, which may provide a new method for salvage treatment of patients with advanced metastatic solid tumors.

Radiotherapy, as an important means of tumor treatment, plays a significant role in the treatment of cervical cancer. However, the ovaries are highly sensitive to radiation, which is prone to appear radiation-related injuries, leading to ovarian dysfunction and loss of fertility in young female patients, seriously affecting their physical and mental health. The degree of ovarian injury is influenced by various factors such as the dose, volume, and duration of radiation exposure to the ovaries, as well as the patient's age. Ovarian displacement and advancements in radiotherapy techniques can significantly relieve radiation-related ovarian injury. Currently, drug protection techniques are still immature, and new fertility preservation methods are receiving increasing attention but require further improvement. This article reviewed the research progress in the molecular mechanisms, prevention strategies, and new fertility preservation techniques for ovarian injury related to cervical cancer radiotherapy, aiming to provide a reference for ovarian function protection during radiotherapy for young cervical cancer patients.

OBJECTIVE To explore the new indications and key mechanism of Bazi Bushen capsule(BZBS)by network pharmacology and in vitro experiment.METHODS The potential tar-get profiles of the components of BZBS were pre-dicted.Subsequently,new indications for BZBS were predicted by disease ontology(DO)enrich-ment analysis and initially validated by GO and KEGG pathway enrichment analysis.Further-more,the therapeutic target of BZBS acting on AD signaling pathway were identified by intersec-tion analysis.Two Alzheimer's disease(AD)cell models,BV-2 and SH-SY5Y,were used to pre-liminarily verify the anti-AD efficacy and mecha-nism of BZBS in vitro.RESULTS In total,1499 non-repeated ingredients were obtained from 16 herbs in BZBS formula,and 1320 BZBS targets with high confidence were predicted.Disease enrichment results strongly suggested that BZBS formula has the potential to be used in the treat-ment of AD.In vitro experiments showed that BZ-BS could significantly reduce the release of TNF-α and IL-6 and the expression of COX-2 and PSEN1 in A β 25-35-induced BV-2 cells.BZBS reduced the apoptosis rate of A β 25-35 induced SH-SY5Y cells,significantly increased mitochon-drial membrane potential,reduced the expres-sion of Caspase3 active fragment and PSEN1,and increased the expression of IDE.CONCLU-SIONS BZBS formula has a potential use in the treatment of AD,which is achieved through regu-lation of ERK1/2,NF-κB signaling pathways,and GSK-3β/β-catenin signaling pathway.Further-more,the network pharmacology technology is a feasible drug repurposing strategy to reposition new clinical use of approved TCM and explore the mechanism of action.The study lays a foun-dation for the subsequent in-depth study of BZBS in the treatment of AD and provides a basis for its application in the clinical treatment of AD.

Patients with severe or critical coronavirus disease 2019 (COVID-19) are at high risk of death primarily due to respiratory failure caused by the cytokine storm in pulmonary tissues. The treatment response of these patients remains limited. Recently, low-dose radiation therapy (LDRT) has been clinically adopted to treat severe or critical COVID-19 patients in multiple medical centers abroad, indicating high feasibility and effectiveness. However, the mechanism and optimal radiation dose are still incompletely clear. This paper reviews the radiobiological mechanism, effectiveness, adverse reactions, and radiotherapy dose of LDRT in the treatment of severe or critical COVID-19 patients, aiming to better understand the clinical benefits and adverse reactions of LDRT.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.