The multimorbidity of rheumatoid arthritis （RA） and periodontitis （PD） has drawn increasing attention， as both conditions are characterized by chronic inflammation， immune dysregulation， and progressive bone destruction. Modern research confirms that PD is a significant risk factor for RA development， and their coexistence mutually exacerbates disease progression. However， traditional Chinese medicine （TCM） currently lacks a systematic theoretical explanation for this complex multimorbid relationship. This study， based on the TCM theory of abnormal collateral， thoroughly examines the intrinsic connection between RA and PD multimorbidity， proposing "abnormal collateral as the pivot， with accumulated toxins eroding bone" as the core TCM pathogenesis. The research elucidates PD as the "origin of abnormal collateral"， where its pathogens act as toxic factors that invade the joints through collaterals， triggering RA via mechanisms such as molecular mimicry. The dynamic pathological progression of RA-PD multimorbidity can be described as follows： the displacement of Ying and Wei at the microscopic level manifests as immune hyperactivation， leading to collateral malnutrition； heat-toxins traversing collaterals induce collateral hyperactivity， resulting in pathological angiogenesis； ultimately， toxin accumulation at the pivotal abnormal collateral site erodes bone， activating the receptor activator of nuclear factor kappa-B ligand （RANKL）-receptor activator of nuclear factor kappa-B （RANK） signaling pathway-driven osteoclast differentiation. This theoretical framework innovatively integrates modern findings in oral microbiology， immune-inflammation， and bone metabolism， offering a holistic and dynamic perspective to understand the complexity of multimorbidity. Given the limited efficacy of current periodontal treatments for RA and the scarcity of reported TCM compound interventions for multimorbidity， the abnormal collateral theory proposes a systematic intervention strategy centered on "governing diseases through collaterals and regulating collaterals with herbs"， along with TCM therapeutic principles such as "unblocking， clearing， and nourishing collaterals". Potential herbal treatments for multimorbidity are also highlighted. Future research should focus on refining TCM syndrome patterns in multimorbid patients and leveraging omics technologies for deeper exploration， thereby providing a theoretical foundation and research direction for TCM in addressing complex multimorbid conditions.

The multimorbidity of rheumatoid arthritis （RA） and periodontitis （PD） has drawn increasing attention， as both conditions are characterized by chronic inflammation， immune dysregulation， and progressive bone destruction. Modern research confirms that PD is a significant risk factor for RA development， and their coexistence mutually exacerbates disease progression. However， traditional Chinese medicine （TCM） currently lacks a systematic theoretical explanation for this complex multimorbid relationship. This study， based on the TCM theory of abnormal collateral， thoroughly examines the intrinsic connection between RA and PD multimorbidity， proposing "abnormal collateral as the pivot， with accumulated toxins eroding bone" as the core TCM pathogenesis. The research elucidates PD as the "origin of abnormal collateral"， where its pathogens act as toxic factors that invade the joints through collaterals， triggering RA via mechanisms such as molecular mimicry. The dynamic pathological progression of RA-PD multimorbidity can be described as follows： the displacement of Ying and Wei at the microscopic level manifests as immune hyperactivation， leading to collateral malnutrition； heat-toxins traversing collaterals induce collateral hyperactivity， resulting in pathological angiogenesis； ultimately， toxin accumulation at the pivotal abnormal collateral site erodes bone， activating the receptor activator of nuclear factor kappa-B ligand （RANKL）-receptor activator of nuclear factor kappa-B （RANK） signaling pathway-driven osteoclast differentiation. This theoretical framework innovatively integrates modern findings in oral microbiology， immune-inflammation， and bone metabolism， offering a holistic and dynamic perspective to understand the complexity of multimorbidity. Given the limited efficacy of current periodontal treatments for RA and the scarcity of reported TCM compound interventions for multimorbidity， the abnormal collateral theory proposes a systematic intervention strategy centered on "governing diseases through collaterals and regulating collaterals with herbs"， along with TCM therapeutic principles such as "unblocking， clearing， and nourishing collaterals". Potential herbal treatments for multimorbidity are also highlighted. Future research should focus on refining TCM syndrome patterns in multimorbid patients and leveraging omics technologies for deeper exploration， thereby providing a theoretical foundation and research direction for TCM in addressing complex multimorbid conditions.

Attention deficit and hyperactive disorder （ADHD） is the most common neurodevelopmental disorder of childhood. It seriously impairs academic achievement， social interaction， and vocational development， and increases the risk of accidental injury and substance abuse. In some cases， the symptoms may also exert an indirect disruptive effect on public order. Its aetiology involves interactions among genetic， perinatal environmental， and psychosocial factors that cannot be fully disentangled by single clinical studies. Therefore， a systematic evaluation of existing animal models is essential for revealing pathophysiology and developing novel therapies. Using the keywords "attention deficit and hyperactive disorder"， "models， animal"， "validity"， and their English equivalents， we systematically searched PubMed， Web of Science， CNKI， and Wanfang for publications from 2000 to 2025 （retrieving 328 publications） and added further references by citation tracking. Eighty-six rodent ADHD models that provided detailed construction protocols， behavioural assessments， neurobiological mechanisms， or pharmacological data were included and classified into spontaneous genetic， genetically engineered， and environmentally induced paradigms. Their face， construct， and predictive validity were compared. Among spontaneous genetic models， spontaneously hypertensive rats reproduce hyperactivity， impulsivity， and stimulant responses well， yet hypertension and sex differences limit specificity. Acallosal mouse strains link corpus callosum absence to ADHD-like behaviours， but neurotransmitter studies remain scarce. Genetically engineered rodents—including dopamine transporter， neurokinin-1 receptor and mediator complex subunit 23 knockout or conditional gene knockout lines—precisely dissect dopaminergic， noradrenergic， synaptic， or epigenetic pathways， yet generally lack full phenotypic coverage， social-deficit modelling， and comorbidity representation， and are accompanied by adverse effects such as growth retardation or ocular defects. Environmentally induced models employ lead， polychlorinated biphenyls， alcohol， nicotine exposures， 6-hydroxydopamine lesions， neonatal hypoxia， early social isolation， or maternal stress to recapitulate core symptoms. However， dose-schedule standardisation is lacking. Behavioural reversibility diverges from clinical persistence， and non-specific phenotypes such as anxiety or depression are common. Overall， no single paradigm simultaneously achieves high validity across all three dimensions. Currently， ADHD models have progressed from single-factor simulations to multidimensional evaluation， yet significant gaps remain in genetic-background standardisation， sex differences， cross-species translation， and syndrome-differentiation modelling under traditional Chinese medicine. Future directions should integrate genetic， environmental， and epigenetic interactions， establish life-span validation systems， and incorporate computational neuroscience alongside integrative Chinese-Western strategies to enhance clinical relevance and translational utility， thereby providing robust evidence-based support for mechanistic elucidation， drug screening and precision intervention in ADHD.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

ObjectiveTo explore the effect and mechanism of Qigui Didang decoction， formulated based on the principle of Tonifying Deficiency and Unblocking Collaterals， on improving metabolic memory of db/db mice with diabetic nephropathy （DN） through silent information regulator 1 signal regulator 1 （Sirt1）/p53/nuclear factor kappa-B （NF-κB） p65 pathway. MethodsFifteen db/db mice were randomly divided into model group （10 mL·kg^-1·d^-1）， resveratrol group （20 mg·kg^-1·d^-1）， and Qigui Didang decoction group （3.34 g·kg^-1·d^-1） Another five db/m mice were selected as the normal group （10 mL·kg^-1·d^-1）. After the intervention， the kidney weight of each group was measured， and the kidney index （KI） was calculated. Fasting blood glucose （FBG）， creatinine （CRE）， β2-microglobulin （β2-MG）， blood urea nitrogen （BUN）， and cystatin C （CysC） were measured. Renal pathology was observed by hematoxylin-eosin （HE） staining and Masson staining. The mRNA and protein expression levels of Sirt1， NF-κB， tumor suppressor gene p53， interleukin-1β （IL-1β）， and cysteine aspartate protease-3 （Caspase-3） were detected using real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultsCompared with the normal group， the model group showed disordered renal structure， obvious renal damage， and markedly elevated levels of renal function indexes （CRE， β2-MG， BUN， and CysC） （P<0.01）. The KI and blood glucose were significantly increased （P<0.01）， while Sirt1 expression was markedly decreased （P<0.01）. Expression levels of NF-κB p65， p53， IL-1β， and Caspase-3 were increased significantly （P<0.05）. Compared with those in the model group， DN mice treated with Qigui Didang decoction exhibited significantly decreased FBG， improved renal function， and markedly decreased KI （P<0.01）， along with reduced CRE， β2-MG， BUN， and CysC levels （P<0.05）. Protein expression of Sirt1 was significantly upregulated （P<0.05）， while that of NF-κB p65， p53， IL-1β， and Caspase-3 was markedly decreased （P<0.05）. The mRNA expression levels of NF-κB p65， p53， IL-1β， and Caspase-3 were significantly decreased （P<0.05）. The staining results indicate improved renal fibrosis， significantly decreased fiber deposition （P<0.05）， and less inflammatory infiltration in the Qigui Didang decoction group. ConclusionThe findings suggest that Qigui Didang decoction can alleviate the metabolic memory effect of DN， thereby inhibiting renal cell apoptosis and inflammatory response in mice， and improving renal function. The mechanism of action is closely related to the Sirt1/p53/NF-κB p65 signaling pathway.

Objective To understand the disease spectrum of a natural village in an area with high incidence of esophageal cancer to provide a reference for precise prevention and control. Methods From 2008 to 2024, 711 asymptomatic people over the age of 35 years in a natural village with high incidence of esophageal cancer in China were surveyed, and 171 of them were subjected to gastroscopy, biopsy, and pathological examination. All participants were followed up for a long time, and their disease history was recorded. Results A total of 16 years of follow-up were performed, and 703 people were effectively followed up. In 2008, 171 people underwent gastroscopy, and 160 people had biopsy and pathological results in endoscopic screening. By 2024, 76 people had been diagnosed with malignant tumors of 12 different types, and among these people, 45 had esophageal cancer. Conclusion Esophageal cancer remains a significant cause of morbidity and mortality from malignant tumors in this region. Biopsy and pathological examination should be strengthened during gastroscopy, and follow-ups and regular check-ups should be given high importance to reduce the incidence and mortality rates of esophageal cancer.

Abstract Modern western medicine typically focuses on treating specific symptoms or diseases, and traditional Chinese medicine (TCM) emphasizes the interconnections of the body’s various systems under external environment and takes a holistic approach to preventing and treating diseases. Phenomics was initially introduced to the field of TCM in 2008 as a new discipline that studies the laws of integrated and dynamic changes of human clinical phenomes under the scope of the theories and practices of TCM based on phenomics. While TCM Phenomics 1.0 has initially established a clinical phenomic system centered on Zhenghou (a TCM definition of clinical phenome), bottlenecks remain in data standardization, mechanistic interpretation, and precision intervention. Here, we systematically elaborates on the theoretical foundations, technical pathways, and future challenges of integrating digital medicine with TCM phenomics under the framework of “TCM phenomics 2.0”, which is supported by digital medicine technologies such as artificial intelligence, wearable devices, medical digital twins, and multi-omics integration. This framework aims to construct a closed-loop system of “Zhenghou–Phenome–Mechanism–Intervention” and to enable the digitization, standardization, and precision of disease diagnosis and treatment. The integration of digital medicine and TCM phenomics not only promotes the modernization and scientific transformation of TCM theory and practice but also offers new paradigms for precision medicine. In practice, digital tools facilitate multi-source clinical data acquisition and standardization, while AI and big data algorithms help reveal the correlations between clinical Zhenghou phenomes and molecular mechanisms, thereby improving scientific rigor in diagnosis, efficacy evaluation, and personalized intervention. Nevertheless, challenges persist, including data quality and standardization issues, shortage of interdisciplinary talents, and insufficiency of ethical and legal regulations. Future development requires establishing national data-sharing platforms, strengthening international collaboration, fostering interdisciplinary professionals, and improving ethical and legal frameworks. Ultimately, this approach seeks to build a new disease identification and classification system centered on phenomes and to achieve the inheritance, innovation, and modernization of TCM diagnostic and therapeutic patterns.

BACKGROUND: Growing evidence suggests that long non-coding RNAs (lncRNAs) exert pivotal roles in fostering chemoresistance across diverse tumors. Nevertheless, the precise involvement of lncRNAs in modulating chemoresistance within the context of gallbladder cancer (GBC) remains obscure. This study aimed to uncover how lncRNAs regulate chemoresistance in gallbladder cancer, offering potential targets to overcome drug resistance. METHODS: To elucidate the relationship between gemcitabine sensitivity and small nucleolar RNA host gene 1 ( SNHG1 ) expression, we utilized publicly available GBC databases, GBC tissues from Renji Hospital collected between January 2017 and December 2019, as well as GBC cell lines. The assessment of SNHG1, miR-23b-3p, and phosphatase and tensin homolog (PTEN) expression was performed using in situ  hybridization, quantitative real-time polymerase chain reaction, and western blotting. The cell counting kit-8 (CCK-8) assay was used to quantify the cell viability. Furthermore, a GBC xenograft model was employed to evaluate the impact of SNHG1 on the therapeutic efficacy of gemcitabine. Receiver operating characteristic (ROC) curve analyses were executed to assess the specificity and sensitivity of SNHG1. RESULTS: Our analyses revealed an inverse correlation between the lncRNA SNHG1 and gemcitabine resistance across genomics of drug sensitivity in cancer (GDSC) and Gene Expression Omnibus (GEO) datasets, GBC cell lines, and patients. Gain-of-function investigations underscored that SNHG1 heightened the gemcitabine sensitivity of GBC cells in both in vitro and in vivo  settings. Mechanistic explorations illuminated that SNHG1 could activate PTEN -a commonly suppressed tumor suppressor gene in cancers-thereby curbing the development of gemcitabine resistance in GBC cells. Notably, microRNA (miRNA) target prediction algorithms unveiled the presence of miR-23b-3p binding sites within SNHG1 and the 3'-untranslated region (UTR) of PTEN . Moreover, SNHG1 acted as a sponge for miR-23b-3p, competitively binding to the 3'-UTR of PTEN , thereby amplifying PTEN expression and heightening the susceptibility of GBC cells to gemcitabine. CONCLUSION The SNHG1/miR-23b-3p/PTEN axis emerges as a pivotal regulator of gemcitabine sensitivity in GBC cells, holding potential as a promising therapeutic target for managing GBC patients.
Humans ; Deoxycytidine/pharmacology* ; PTEN Phosphohydrolase/genetics* ; Gemcitabine ; RNA, Long Noncoding/metabolism* ; MicroRNAs/genetics* ; Gallbladder Neoplasms/genetics* ; Cell Line, Tumor ; Animals ; Mice ; Drug Resistance, Neoplasm/genetics* ; Mice, Nude ; Antimetabolites, Antineoplastic ; Gene Expression Regulation, Neoplastic

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.