This paper outlines the development of artificial intelligence （AI） and its applications in traditional Chinese medicine （TCM） research， and elucidates the roles and advantages of large language models， knowledge graphs， and natural language processing in advancing syndrome identification， prescription generation， and mechanism exploration. Using spleen-stomach diseases as an example， it demonstrates the empowering effects of AI in classical literature mining， precise clinical syndrome differentiation， efficacy and safety prediction， and intelligent education， highlighting an upgraded research paradigm that evolves from data-driven and knowledge-driven approaches to intelligence-driven models. To address challenges related to privacy protection and regulatory compliance in cross-institutional data collaboration， a "trusted federated evidence-based analysis platform for TCM spleen-stomach diseases" is proposed， integrating blockchain-based smart contracts， federated learning， and secure multi-party computation. The deep integration of AI with privacy-preserving computing is reshaping research and clinical practice in TCM spleen-stomach diseases， providing feasible pathways and a technical framework for building a high-quality， trustworthy TCM big-data ecosystem and achieving precision syndrome differentiation.

AIM: To evaluate the efficacy and safety of 3% diquafosol sodium eye drops in children wearing orthokeratology lenses and with dry eye disease(DED)or at risk of DED.METHODS: Randomized controlled trials. Children with DED or at risk of DED were randomly assigned in a 1:1 ratio to receive either 3% diquafosol sodium eye drops 6 times daily or a blank control at Chongqing Aier Children's Eye Hospital from November 2023 to November 2024. The primary endpoint was the change in the Dry Eye Questionnaire-5(DEQ-5)score from baseline at 12 wk. Secondary assessments included non-invasive breakup time(NIBUT), tear meniscus height, Schirmer's test, corneal fluorescein staining score, and axial length.RESULTS: A total of 80 participants(80 eyes)were enrolled(40 in each group), the average age of the participants was 11.11±1.88 years, with 43 females(54%)and 37 males(46%), and all completed the trial. After 12 wk, the DEQ-5 scores for the diquafosol sodium group and the blank control group were 1.88±2.02 and 2.88±2.79, respectively(P=0.079). The diquafosol sodium group demonstrated a significant improvement in DEQ-5 dryness symptom scores(-0.33±0.66 vs. 0.05±0.81, P=0.023)and NIBUT(6.18±3.73 vs. -1.09±4.40 s, P<0.001)at 12 wk. Additionally, the diquafosol sodium group showed no axial length elongation, in contrast to the blank control group, which exhibited elongation(0.00±0.08 vs. 0.05±0.10 mm, P=0.013). No other significant differences were found in the secondary endpoints. No adverse events occurred during the trial.CONCLUSION: Although no statistically significant improvements were noted in the overall DEQ-5 scores, the 3% diquafosol sodium eye drops significantly improved dryness symptoms and NIBUT when compared to the blank control group.

ObjectiveTo investigate the effect of Toxoplasma gondii infection on copper metabolism in the kidneys of mice. MethodsA total of 80 7-8-week-old C57BL/6 female mice were randomly divided into four groups of 20 mice in each group after one week of adaptation， including Control group， Cu group， TgCtwh6 group and Cu+TgCtwh6 group. Mice that were not infected and fed with normal diet and water were used as the Control group； Mice fed with 1 g/kg of copper chloride processing diet and 0.1% copper chloride water for 60 consecutive days were used as Cu group； Mice infected with 25-30 TgCtwh6 cysts （one of the predominant genotype Chinese 1 in China） fed with normal diet and water were used as the TgCtwh6 group； mice infected with 25-30 TgCtwh6 cysts and fed with a processed diet containing 1 g/kg of copper chloride and water with 0.1% copper chloride for 60 consecutive days were used as the Cu+TgCtwh6 group. ICP-MS was used to determine the changes in copper content in kidney tissues. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of mouse kidney tissue. The number of apoptotic cells was observed by PI staining. Western blot was used to detect the protein expression levels of glutathione peroxidase 4 （GPX4） and superoxide dismutase （SOD1， SOD2）. RT-qPCR was used to detect the mRNA expression of cuproptosis-related genes. ResultsPathological manifestations such as inflammatory cell infiltration in the Cu group and TgCtwh6 group were seen under the microscope， and the inflammatory infiltrating cells of the renal interstitial were reduced in the Cu+TgCtwh6 group， and the pathological manifestations

Objective To analyze the clinical and therapeutic characteristics of Epstein-Barr virus (EBV)-negative posttransplant lymphoproliferative disease (PTLD) with diffuse large B-cell lymphoma (DLBCL) in the context of specific cases and literature. Methods A case of EBV-negative DLBCL (GCB type) after kidney transplantation is reported. The patient was a 45-year-old male who underwent living-related kidney transplantation in 2016 and has been receiving triple immunosuppressive therapy with tacrolimus, mycophenolate mofetil and methylprednisolone since then. In 2024, the patient presented with intermittent fever, night sweats and gastrointestinal symptoms. The diagnosis was confirmed by endoscopic pathology, immunohistochemical staining and positron emission tomography/computed tomography. The R-CDOP regimen (rituximab + cyclophosphamide + liposomal doxorubicin + vincristine + dexamethasone) was used for treatment. Results The patient was diagnosed with EBV-negative DLBCL (GCB type, Ann Arbor stage Ⅳ B). After 4 cycles of R-CDOP chemotherapy, the efficacy assessment was partial remission, and the transplant kidney function remained stable. Conclusions For EBV-negative PTLD after kidney transplantation, it is necessary to break through the "virus-dependent" diagnostic thinking. In clinical practice, the focus should be on protecting the transplant kidney, and individualized treatment plans should be developed for patients.

LIU Wansu， as the foremost of the four great masters of the Jin-Yuan period， established the "theory of fire-heat'' and extended the fire-heat pathogenesis framework to the field of stroke， thereby forming the theory of ''fire-heat inducing stroke''. This achieved a paradigmatic shift in stroke etiology from ''exogenous wind inducing stroke'' to ''fire-heat inducing stroke''. This paper systematically reviews the developmental trajectory of LIU Wansu's ''fire-heat inducing stroke'' theory and explores the social background， academic origins， and core connotations of its theoretical construction. The study found that， based on the ''Nineteen Pathomechanisms'' in the Huangdi's Internal Classic （Huang Di Nei Jing） and combined with clinical practice， LIU Wansu proposed that fire-heat is the fundamental cause of stroke， and that the Six Climatic Factors and the Five Zhi-Emotions can all transform into fire. He further constructed a stratified syndrome differentiation and therapeutic system centered on clearing heat and purging fire， emphasizing differentiated treatment of exterior and interior syndromes， Six Meridians syndrome differentiation， and seasonally adjusted medication. This theory not only resolved the diagnostic and therapeutic dilemmas of febrile epidemic diseases during the Jin-Yuan period， but also exerted a profound influence on later physicians such as ZHANG Zihe and ZHU Danxi， thereby promoting the pluralistic development of stroke theory in traditional Chinese medicine （TCM）. Modern pharmacological research provides solid scientific evidence， confirming that the ''fire-heat'' pathological state is highly associated with key mechanisms such as excessive inflammatory responses， oxidative stress， and excitatory amino acid toxicity following cerebral ischemia. Heat-clearing and fire-purging prescriptions and agents， such as Huanglian Jiedu Tang and baicalin， can exert multi-target neuroprotective effects by regulating inflammatory signaling， enhancing antioxidant enzyme activity， and balancing neurotransmitters. This not only verifies the scientific basis of the ''fire-heat inducing stroke'' theory from a modern biological perspective but also provides conclusive evidence for the clinical application of heat-clearing and fire-purging therapy. LIU Wansu's ''fire-heat inducing stroke'' theory represents a major milestone in the historical understanding of stroke pathogenesis， and its academically transitional insights continue to hold core guiding value for the pattern identification and treatment of ischemic stroke today.

This article systematically analyzes the historical evolution of the name， origin， medicinal parts， producing area， harvesting and processing， nature， flavor and efficacy of Piperis Longi Fructus by referring to the materia medica， medical books， and prescription books of past dynasties， combined with the relevant modern literature， in order to provide a basis for the development and utilization of famous classical formulas containing this herb. According to the herbal textual research， the name of Piper longum first appeared in Nanfang Caomuzhuang， and it also has other aliases such as Biboli， Halou， and Hujiaohua. Historically， the origin of Piperis Longi Fructus has been P. longum of the Piperaceae family. In ancient times， both the fruit and root were used as medicine， and since the Republic of China， the fruit has been mainly used as medicine. The medicinal part is the dried， nearly ripe or ripe fruit spikes. Piperis Longi Fructus is native to India and has been introduced into China since the Tang dynasty. In the Ming dynasty， Bencao Pinhui Jingyao clearly stated that the genuine producing area was "Duanzhou"， present-day Zhaoqing in Guangdong province. Nowadays， it is planted in Guangdong， Guangxi， Hainan， Yunnan and other regions. Historically and currently， harvesting occurs in autumn. The ancient processing method uniformly involved removing the stems， soaking in the sourest vinegar overnight， baking， and scraping off the peels and grains with a knife until clean. In modern times， impurities are removed， and it is dried in the sun and crushed when used. The properties， functions and applications of P. longum are basically the same in ancient and modern times. It tastes pungent， is warm in nature， and non-toxic. It has the effects of warming the middle-jiao to dispel cold， lowering Qi and relieving pain， and is used for cold pain in the epigastrium and abdomen， vomiting， diarrhea， chest pain， headache， and toothache. Based on the research results， it is recommended that when developing famous classical formulas containing Piperis Longi Fructus， the dried nearly ripe or ripe fruit spikes of P. longum should be used. If there are no clear processing requirements， it is recommended to use the raw products for medicinal use， and the specific processing methods can refer to the relevant requirements under Piperis Longi Fructus in the 2025 edition of the Pharmacopoeia of the People's Republic of China. If processing requirements such as soaking in vinegar and peeling are clearly specified， it is recommended to follow the ancient methods.

LIU Wansu， as the foremost of the four great masters of the Jin-Yuan period， established the "theory of fire-heat'' and extended the fire-heat pathogenesis framework to the field of stroke， thereby forming the theory of ''fire-heat inducing stroke''. This achieved a paradigmatic shift in stroke etiology from ''exogenous wind inducing stroke'' to ''fire-heat inducing stroke''. This paper systematically reviews the developmental trajectory of LIU Wansu's ''fire-heat inducing stroke'' theory and explores the social background， academic origins， and core connotations of its theoretical construction. The study found that， based on the ''Nineteen Pathomechanisms'' in the Huangdi's Internal Classic （Huang Di Nei Jing） and combined with clinical practice， LIU Wansu proposed that fire-heat is the fundamental cause of stroke， and that the Six Climatic Factors and the Five Zhi-Emotions can all transform into fire. He further constructed a stratified syndrome differentiation and therapeutic system centered on clearing heat and purging fire， emphasizing differentiated treatment of exterior and interior syndromes， Six Meridians syndrome differentiation， and seasonally adjusted medication. This theory not only resolved the diagnostic and therapeutic dilemmas of febrile epidemic diseases during the Jin-Yuan period， but also exerted a profound influence on later physicians such as ZHANG Zihe and ZHU Danxi， thereby promoting the pluralistic development of stroke theory in traditional Chinese medicine （TCM）. Modern pharmacological research provides solid scientific evidence， confirming that the ''fire-heat'' pathological state is highly associated with key mechanisms such as excessive inflammatory responses， oxidative stress， and excitatory amino acid toxicity following cerebral ischemia. Heat-clearing and fire-purging prescriptions and agents， such as Huanglian Jiedu Tang and baicalin， can exert multi-target neuroprotective effects by regulating inflammatory signaling， enhancing antioxidant enzyme activity， and balancing neurotransmitters. This not only verifies the scientific basis of the ''fire-heat inducing stroke'' theory from a modern biological perspective but also provides conclusive evidence for the clinical application of heat-clearing and fire-purging therapy. LIU Wansu's ''fire-heat inducing stroke'' theory represents a major milestone in the historical understanding of stroke pathogenesis， and its academically transitional insights continue to hold core guiding value for the pattern identification and treatment of ischemic stroke today.

This article systematically analyzes the historical evolution of the name， origin， medicinal parts， producing area， harvesting and processing， nature， flavor and efficacy of Piperis Longi Fructus by referring to the materia medica， medical books， and prescription books of past dynasties， combined with the relevant modern literature， in order to provide a basis for the development and utilization of famous classical formulas containing this herb. According to the herbal textual research， the name of Piper longum first appeared in Nanfang Caomuzhuang， and it also has other aliases such as Biboli， Halou， and Hujiaohua. Historically， the origin of Piperis Longi Fructus has been P. longum of the Piperaceae family. In ancient times， both the fruit and root were used as medicine， and since the Republic of China， the fruit has been mainly used as medicine. The medicinal part is the dried， nearly ripe or ripe fruit spikes. Piperis Longi Fructus is native to India and has been introduced into China since the Tang dynasty. In the Ming dynasty， Bencao Pinhui Jingyao clearly stated that the genuine producing area was "Duanzhou"， present-day Zhaoqing in Guangdong province. Nowadays， it is planted in Guangdong， Guangxi， Hainan， Yunnan and other regions. Historically and currently， harvesting occurs in autumn. The ancient processing method uniformly involved removing the stems， soaking in the sourest vinegar overnight， baking， and scraping off the peels and grains with a knife until clean. In modern times， impurities are removed， and it is dried in the sun and crushed when used. The properties， functions and applications of P. longum are basically the same in ancient and modern times. It tastes pungent， is warm in nature， and non-toxic. It has the effects of warming the middle-jiao to dispel cold， lowering Qi and relieving pain， and is used for cold pain in the epigastrium and abdomen， vomiting， diarrhea， chest pain， headache， and toothache. Based on the research results， it is recommended that when developing famous classical formulas containing Piperis Longi Fructus， the dried nearly ripe or ripe fruit spikes of P. longum should be used. If there are no clear processing requirements， it is recommended to use the raw products for medicinal use， and the specific processing methods can refer to the relevant requirements under Piperis Longi Fructus in the 2025 edition of the Pharmacopoeia of the People's Republic of China. If processing requirements such as soaking in vinegar and peeling are clearly specified， it is recommended to follow the ancient methods.

Objective To systematically analyze the characteristics of the disease burden of hypertensive heart disease (HHD) in the elderly (≥60 years) globally and in China from 1990 to 2021, and to predict its future trends from 2022 to 2040, with the aim of providing data support for optimizing comprehensive prevention and control strategies for HHD. Methods Based on the Global Burden of Disease (GBD) 2021 database, the number of prevalent cases and disability-adjusted life years (DALYs) of HHD in the elderly were extracted for the world, China, and five regions categorized by sociodemographic index (SDI). Joinpoint regression was used to analyze the temporal trends of age-standardized prevalence rate and age-standardized DALYs rate of HHD in the elderly. A three-factor decomposition method was applied to evaluate the relative contributions of aging, population growth, and epidemiological changes to the variations in the elderly HHD burden. Additionally, a Bayesian age-period-cohort model was used to predict the elderly HHD burden from 2022 to 2040. Results In 2021, the number of prevalent elderly HHD cases reached 10 283 000 globally and 3 412 400 in China, representing increases of 179.20% and 159.20% respectively, compared with 1990. The DALYs of elderly HHD were 18 812 700 person-years globally and 4 731 400 person-years in China, rising by 76.08% and 29.45% respectively from 1990. Meanwhile, the growth rates of the number of prevalent cases and DALYs of elderly HHD varied across different SDI regions. From 1990 to 2021, the age-standardized prevalence rate of elderly HHD in China, as well as the age-standardized DALYs rate of elderly HHD both globally and in China, showed significant downward trends (all average annual percentage changes<0, all P<0.001). In 2021, the 70-74 years age group accounted for the highest proportion of prevalent cases and DALYs of elderly HHD, both globally and in China. Decomposition analysis revealed that population growth was the dominant factor driving the increase in the elderly HHD burden across all regions. The prediction model results indicated that the number of prevalent cases and DALYs of elderly HHD would continue to rise globally and in China from 2022 to 2040, with the growth rate of the elderly HHD burden in China between 2021 and 2040 expected to exceed the global average. Conclusion Over the past 32 years, although the age-standardized disease rates of elderly HHD have mainly shown a downward trend globally and in China, the absolute number of the disease burden has increased substantially. The projection model indicates a continued upward trajectory, with the growth rate in China higher than the global average. Therefore, there is an urgent need to implement precise prevention and control strategies to effectively mitigate the disease burden of elderly HHD.

Objective: To characterize longitudinal trajectories of testicular development in boys and breast development in girls, so as to provide reference data for understanding patterns of pubertal sexual maturation. Methods: Based on the Shanghai Pudong New Area Cohort Study on Growth, Development and Health in Children and Adolescents, a baseline survey was conducted in 2020 using a mult stage cluster random sampling method. A total of 2 184 children who completed all follow ups during the primary school period from 13 elementary schools in Pudong New Area,Shanghai,with annual follow ups during 2021-2025. Testicular volume and Tanner stage of breast development were assessed by professional physicians using standardized visual inspection and palpation. The age distribution of testicular volume and breast development was fitted by using cumulative link mixed models and Turnbull s nonparametric maximum likelihood estimation method. Results: Median ages for testicular volumes of 2, 3, 4 and 5 mL in boys were 7.07, 9.24, 10.29, and 11.57 years old, respectively. Median ages for Tanner breast stages Ⅱ, Ⅲ, Ⅳ, and Ⅴ in girls were 8.55 , 10.17, 11.18, and 13.78 years old, respectively. Based on overweight and obesity, stratified analysis showed that earlier pubertal onset among overweight/obesity children, and the key milestones for pubertal initiation were testicular volume reaching 4 mL in boys and breast Tanner II in girls for 10.29, 10.83; 8.18, 9.00 years. Conclusion Overweight and obesity are associated with earlier pubertal initiation,but there are certain gender and developmental stage specific patterns.