Mainly based on the "constitution-syndrome-disease location correlation" approach， this study constructs a traditional Chinese medicine （TCM） framework for understanding hypertension comorbidities. From the perspective of shared constitutional predispositions and similar pathomechanistic characteristics， hypertension comorbidity should not be regarded as a simple aggregation of multiple diseases. Rather， it is generally rooted in biased constitutions such as yin-deficiency， qi-deficiency， yang-deficiency， phlegm-dampness， dampness-heat， and blood-stasis constitutions， accompanied by the long-term interplay of pathogenic mechanisms involving wind， fire， phlegm， stasis， and deficiency， and gradually manifests as comorbidities affecting different systems through the evolution of disease locations related to the liver， heart， spleen， and kidney. On this basis， cardiac-， cerebral-， renal-， and metabolic-related comorbidities are taken as the major categories， and their characteristics related to constitution， syndrome， and disease location are systematically summarized to clarify the correspondence between shared pathomechanisms and predominant disease locations， and to propose corresponding prevention and treatment strategies. This framework further incorporates constitution-based stratification into risk stratification for prospective intervention， and takes syndrome as the central link in developing multi-disease treatment strategies such as boosting qi and activating blood， as well as resolving phlegm and unblocking collaterals. A clinical pathway is thereby proposed， encompassing constitution assessment， syndrome differentiation， comorbidity risk stratification， integrated traditional Chinese and western medicine intervention， and follow-up feedback. This study aims to provide a reference for the theoretical development and collaborative management of hypertension comorbidities in TCM.

The abnormal accumulation of neutrophil extracellular traps （NETs） can promote the initiation and progression of pancreatic cancer， which is considered a potential therapeutic target for this disease. The Miraculous Pivot·Inquiry About Statement （《灵枢·口问》） have recorded the concept of "defensive qi stagnation". Based on the recognition that the function of defensive qi is similar to the immune function of neutrophils， and combining traditional Chinese medicine theory with clinical practice， it is proposed that the abnormal accumulation of NETs may be a pathological product of "defensive qi stagnation"， with the spleen being the critical site of pathology. Further exploring the application strategy of cleaning spleen and restoring defensive qi method in pancreatic cancer treatment， it is proposed to employ three approaches such as dredging method to eliminate spleen stagnation and inhibit pancreatic cancer proliferation， cleaning method to remove spleen dampness and suppress the inflammatory micro-environment， and tonifying method to strengthen Weiqi and to improve the immune microenvironment， which aims to provide new insights for the clinical treatment of pancreatic cancer with traditional Chinese medicine.

Alzheimer's disease(AD)is the most common neurodegenerative disease in the elderly,and its main pathological manifestations include senile plaques formed by β-amyloid deposition and neuronal fibrillar nodules formed by hyperphosphorylation of tau proteins.Lysosome is an important organelle in eukaryotic cells,containing a variety of hydrolytic enzymes that can break down proteins and other biomolecules.It is closely related to intracellular transport and autophagy,and is important for maintaining cellular homeostasis.This review summarizes the interaction between lysosomal dysfunction and the development and progression of AD and the potential therapeutic mechanisms in treating AD by regulating and restoring the functions of lysosomes.Lysosomal dysfunction can lead to neurodegenerative diseases such as AD.Modulation of lysosomal function is a promising treatment strategy for AD.It is expected that more drugs and therapeutic regimens based on this mechanism can be used in the clinical treatment for AD patients in the future.

OBJECTIVE: To characterize a glycosyltransferase (RpUGT1) from Rheum palmatum and investigate its specificity toward flavonoid compounds. METHODS: The RpUGT1 was expressed in Escherichia coli and screened for catalytic activity against a range of flavonoid substrates using a high-throughput HPLC assay method. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) were used to determine the structure of the product. Homology modeling, molecular docking analyses and site-directed mutagenesis studies were conducted to identify key residues responsible for its function. RESULTS: The recombinant RpUGT1 protein exhibited catalytic activity towards various flavonoids. Notably, RpUGT1 catalyzed the glycosylation of isorhamnetin to form 3-O-glucoside and kaempferol to form 7-O-glucoside, utilizing uridine diphosphate (UDP) glucose as the sugar donor. The homology modeling and molecular docking analyses identified key residues responsible for its activity. Subsequent site-directed mutagenesis studies highlighted the crucial role of K307 in catalysis. CONCLUSION These discoveries offer valuable perspectives on the role of the UGT family and establish a groundwork for forthcoming research on the synthesis of flavonoids in plants.

Objective:To compare the preliminary efficacy and adverse events of chemoradiotherapy (CRT) with or without immunotherapy in bladder preservation therapy for localized muscle-invasive bladder cancer (MIBC) confined to the pelvis.Methods:Clinical data of 60 patients with MIBC who received CRT with or without immunotherapy for bladder preservation at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to June 2024 were retrospectively analyzed. Patients were divided into CRT plus immunotherapy group and CRT-alone group. Survival outcomes, bladder function preservation, recurrence and metastasis, as well as early and late radiation toxicities were evaluated. The Mann-Whitney U test was used for between-group comparisons. Overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were estimated by the Kaplan-Meier method, and survival rates were compared by the log-rank test. Results:In the CRT plus immunotherapy group ( n=23), the median follow-up was 20 months. The median OS and median PFS were not reached. The 2-year OS, PFS, LRFS, and DMFS rates were 95.7%, 70.7%, 70.7%, and 92.9%, respectively, and 22 patients (96%) preserved normal bladder function. Patients with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 had significantly higher 1-year PFS rate than those with CPS <1 (100% vs. 66.7%, P=0.004). In the CRT-alone group ( n=37), the median follow-up was 37 months, with median OS and PFS of 68 and 19 months, respectively. The 2-year OS, PFS, LRFS, and DMFS rates were 92.0%, 41.1%, 60.9% and 81.5%, respectively, and 33 patients (89%) preserved normal bladder function. Compared with the CRT-alone group, the CRT plus immunotherapy group showed a significant improvement in PFS ( χ2=4.38, P=0.036), while no significant differences were observed in OS, LRFS, or DMFS (all P>0.05). The incidence of acute hematologic toxicity in the CRT plus immunotherapy group and CRT-alone group were 52% (12/23), 27% (10/37) respectively, and late genitourinary toxicity was 22% (5/23), 8% (3/37), respectively, with no significant differences in overall acute or late toxicities (all P>0.05). Conclusions:For localized MIBC, bladder preservation with CRT combined with immunotherapy significantly improves PFS compared with CRT alone, while maintaining comparable safety. The PD-L1 status may serve as a favorable predictor for immunotherapy efficacy.

Objective To explore influencing factors of subsequent fracture among elderly osteoporotic patients and provide a basis for improving the management and early intervention after osteoporotic fracture.Methods A total of 14 349 elderly patients with osteoporotic fracture in 594 hospitals across 31 provinces(autonomous regions and municipalities)were selected by convenience sampling method from September to December 2023.A general information questionnaire and a clinical characteristics of fracture questionnaire were used.The univariate analysis and logistic regression were used to clarify the influencing factors and gender differences.Results A total of 11364 valid questionnaires were collected,with a valid questionnaire recovery rate of 79.20％.Gender,age,occupation,education,marital status,family history of osteoporosis,comorbid osteoarthropathies/rheumatism/ophthalmopathies,bone mineral density,risk of fall,risk of fracture grade,reasons and site for first fracture,whether to use walking aid and receive home rehabilitation guidance were associated with the occurrence of subsequent fracture.Gender comparisons found that widowhood,family history of osteoporosis,comorbid rheumatism,vertebral fracture,alcohol consumption,fall or no causative factor triggering the fracture,and educational level,home rehabilitation instruction were associated with the risk of subsequent fracture only in women(P＜0.05).Smoking was associated with the risk of subsequent fracture only in men(P＜0.05).Conclusion Osteoporotic subsequent fracture in the elderly is affected by multidimensional factors,with significant gender differences.The surveillance of key populations should be strengthened in prevention,control and intervention.

Objective To investigate the current status and analyze the factors affecting the osteoporosis knowledge among orthopedic nurses,and to provide references for improving osteoporosis knowledge among orthopedic nurses.Methods We investigated 5 681 orthopedic nurses from 621 hospitals in 31 provinces(autonomous regions/municipalities)using a convenient sampling method from September 2023 to November 2023.We collected information using a general information questionnaire and osteoporosis knowledge assessment tool.We used univariate and multivariate logistic regression to identify risk factors.Results A total of 5 204 orthopedic nurses were included.The total mean score of osteoporosis knowledge assessment tool of nurses was[13.00(12.00,14.00)],and 23.48％nurses had a low level of osteoporosis awareness.Logistic regression analysis showed that the age,title and position of the nurses,location of the hospital,the level of the hospital,whether to conduct the fracture liaison service/to set up the refracture prevention team,whether to use calcium tablets/vitamin D,whether to carry out anti-osteoporosis drug therapy,and whether to conduct topical lectures on osteoporosis or secondary fractures,were the factors that affected orthopedic nurses'knowledge of osteoporosis(P＜0.05).Conclusion The osteoporosis knowledge of orthopedic nurses needs to be improved.Nursing managers should carry out personalized interventions from both hospital and nurse levels to improve the osteoporosis knowledge of orthopedic nurses in our country.

Objective A cross-sectional survey on the postoperative home care status and barriers was conducted among elderly patients with osteoporotic fractures nationwide,in order to provide a basis for promoting the improvement of standardized home care for elderly patients with osteoporotic fractures.Methods From October to November 2023,a survey on the current situation and barriers of home environment protection was conducted among elderly patients with osteoporotic fractures in the orthopedic wards of 594 hospitals across 31 provinces(autonomous regions/municipalities directly under the central government)using a convenience sampling method.Results A total of 14,349 questionnaires were distributed,and 12,496 valid questionnaires were collected,resulting in an effective response rate of 87.09％.Among the patients,5,502 cases(44.03％)had implemented home-based prevention and treatment of osteoporosis before the fracture.2 095(16.77％)of the patients experienced a subsequent fracture,of which 65.11％of the patients who experienced a subsequent fracture received medication intervention after the initial fracture,while 19.86％of the patients who experienced a subsequent fracture did not comply with the treatment for osteoporosis after the initial fracture.Additionally,77.66％(n=1 627/2 095)of the patients received community medical services after the initial fracture.Barriers to care factors in the home environment after fracture from the patient's perspective presented the complexity of the social-ecological system model in 6 dimensions at 2 levels:micro(basic personal situation,physiological factors,psychological factors,and behavioural factors),and meso(social support factors,and healthcare worker factors).Conclusion In the vast majority of elderly patients in China,before osteoporotic fracture,home-based measures to prevent osteoporosis have not been adequately implemented;after the initial osteoporotic fracture,the pathway of re-fracture prevention and management in the patient's home environment is not yet complete and its popularity needs to be improved;the barriers to home care faced by elderly patients with osteoporotic fracture are complex.It is recommended to promote effective linkages among hospitals,community health centres and families to strengthen the closed-loop management of re-fracture prevention and management.

This paper summarized the clinical experience of Prof. LI Diangui in treating gastroesophageal reflux disease （GERD） based on the theory of turbidity-toxin in liver. It is believed that internal accumulation of turbidity-toxin and liver depression with stomach counterflow are the main pathogenesis of GERD， and thus the therapeutic methods of resolving turbidity and resolving toxins， regulating the liver and harmonizing the stomach are proposed. In clinical practice， GERD is divided into the early stage， middle stage and late stage. For the early stage， the modified Huazhuo Shugan Hewei Formula （化浊疏肝和胃方） is used to regulate qi and remove turbidity， soothe the liver and harmonize the stomach； for the middle stage， the modified Huazhuo Qingre Zhisuan Formula （化浊清热制酸方） is applied to clear heat， direct the turbid downward， and resolve toxins； for the late stage， the modified Yiwei Decoction （益胃汤） is adopted to replenish qi， nourish yin and simultaneously resolve turbidity-toxin. Throughout the treatment process， attention should be paid to protecting the spleen and stomach， and the medication could be modified according to changes of individual condition.

The key pathological feature of age-related macular degeneration(AMD)is dysfunction of retinal pigment epithelial cells.Cell adhesion,serving as the biological basis for dynamic interactions between cells and between cells and the extracellular matrix,regulates tissue homeostasis through transmembrane signaling networks mediated by adhesion molecules.Studies have shown that the aberrant expression of E-cadherin,which offers advantages such as dynamic plas-ticity,tissue specificity,and signal transduction capability,is closely associated with the pathological mechanism of AMD.Targeting E-cadherin-related molecules may thus serve as a potential strategy for AMD intervention.This article reviews re-cent advances in the molecular regulatory mechanisms and therapeutic research concerning E-cadherin in AMD,aiming to provide a theoretical basis for its clinical translation.