With the rapid development of artificial intelligence, computational pathology has been seamlessly integrated into the entire clinical workflow, which encompasses diagnosis, treatment, prognosis, and biomarker discovery. This integration has significantly enhanced clinical accuracy and efficiency while reducing the workload for clinicians. Traditionally, research in this field has depended on the collection and labeling of large datasets for specific tasks, followed by the development of task-specific computational pathology models. However, this approach is labor intensive and does not scale efficiently for open-set identification or rare diseases. Given the diversity of clinical tasks, training individual models from scratch to address the whole spectrum of clinical tasks in the pathology workflow is impractical, which highlights the urgent need to transition from task-specific models to foundation models (FMs). In recent years, pathological FMs have proliferated. These FMs can be classified into three categories, namely, pathology image FMs, pathology image-text FMs, and pathology image-gene FMs, each of which results in distinct functionalities and application scenarios. This review provides an overview of the latest research advancements in pathological FMs, with a particular emphasis on their applications in oncology. The key challenges and opportunities presented by pathological FMs in precision oncology are also explored.
Humans ; Precision Medicine/methods* ; Medical Oncology/methods* ; Artificial Intelligence ; Neoplasms/pathology* ; Computational Biology/methods*

The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

Traditional Chinese medicine(TCM), a treasure of the Chinese nation, contains abundant chemical components and demonstrates unique pharmacological activities, showing important values in clinical applications. With profound connotations and broad application prospects, TCM urgently needs us to further explore and conduct systematic research. Puerarin is a small-molecule natural isoflavonoid carbon glycoside extracted from plants of Pueraria. It is also the main active ingredient of Puerariae Lobata Radix, a Chinese herbal medicine with both medicinal and edible values. Puerarin has a variety of pharmacological effects such as blood pressure-lowering, anti-atherosclerosis, anti-ischemia-reperfusion injury, antithrombotic, anti-tumor, anti-inflammatory, liver-protecting, nerve cell-protecting, and intestinal microbiota-regulating effects. It is also an active ingredient that has been widely studied. This article comprehensively reviews the research progress in the pharmacological effects and molecular mechanisms of puerarin over the years, aiming to provide references and theoretical support for the in-depth research and development as well as clinical application of puerarin.
Isoflavones/chemistry* ; Humans ; Animals ; Drugs, Chinese Herbal/chemistry* ; Pueraria/chemistry*

OBJECTIVE: To investigate the effectiveness of free palmaris longus tendon graft reconstruction in the treatment of gouty tophus erosion lesions in flexor tendon of wrist and hand. METHODS: A retrospective analysis was conducted on 8 patients with gouty tophus erosion lesions in flexor tendon of wrist and hand who underwent free palmaris longus tendon graft reconstruction between June 2017 and December 2023. All patients were male, aged 22-65 years, with an average of 45.9 years. The duration of gout history ranged from 2 to 18 years, with an average of 8.8 years. The duration from the discovery of gouty tophus to operation ranged from 12 to 26 months, with an average of 17.6 months. The gouty tophus eroded the flexor pollicis longus tendon in 4 cases, with Verdan flexor tendon zones being Ⅰ-Ⅱ in 1 case and Ⅳ-Ⅴ in 3 cases. The flexor digitorum profundus tendons were affected in 2 cases for the index finger, 1 for the middle finger, and 1 for the ring finger, all located in zone Ⅳ-Ⅴ. The long axis of the gouty tophus ranged from 2.3 to 4.5 cm, with an average of 3.4 cm. All 8 patients presented with limited finger flexion and extension. Among them, 4 cases were accompanied by median nerve compression symptoms, and 1 case had associated bone and joint destruction in the hand. The total active motion (TAM) of the affected finger was (81.3±30.2)° before operation according to the hand function evaluation criteria for tendon repair by the Chinese Society of Hand Surgery of the Chinese Medical Association, and the functional evaluation was poor. The harvested palmaris longus tendon intraoperatively was 7-9 cm in length. RESULTS: Surgical incisions in all 8 patients healed by first intention, with no infections, graft non-union, or significant adhesion complications. All patients were followed up 8-25 months, with an average of 14.8 months. Numbness symptoms resolved in all 4 patients who presented with median nerve compression symptoms. Patients did not experience wrist pain or other discomfort, and function was not compromised. At last follow-up, according to the hand function evaluation criteria for tendon repair by the Chinese Society of Hand Surgery of the Chinese Medical Association, the TAM of 8 patients was (197.5±55.8)°, which significantly improved when compared with that before operation ( t=11.638, P<0.001); the hand function of 1 patient with gouty tophus in zone Ⅰ-Ⅱ flexor pollicis longus tendon was good, and the other 7 patients were excellent. CONCLUSION Free palmaris longus tendon graft reconstruction demonstrates good effectiveness in treating gouty tophus erosion lesions in flexor tendon of wrist and hand.
Humans ; Middle Aged ; Male ; Adult ; Tendons/surgery* ; Retrospective Studies ; Aged ; Gout/complications* ; Wrist/surgery* ; Plastic Surgery Procedures/methods* ; Hand/surgery* ; Treatment Outcome ; Young Adult

OBJECTIVE: To explore the effectiveness of multi-segment inverted Y-shaped vein transplantation using the anterior lateral malleolar venous network for repair of amputated palm injury distal to the superficial palmar arch. METHODS: Between September 2018 and July 2023, 5 patients with amputated palm injury distal to the superficial palmar arch were treated. There were 3 males and 2 females with an average age of 35.4 years (range, 29-52 years). The time from injury to admission was 1-6 hours (mean, 3.2 hours). The multi-segment inverted Y-shaped vein transplantation in the anterior lateral malleolar venous network were used to repair the common and proper palmar digital arteries; the another anterior lateral malleolar venous network was used to repair the dorsal vein of the hand. The soft tissue defect of dorsal hand in 1 patient was repaired with the pedicled ilioinguinal flap, and the wound at the donor site was directly sutured. Postoperative treatment included anti-infection therapy, antispasmodic therapy, and thrombosis prevention measures. RESULTS: The partial necrosis of the fingertip of the thumb occurred in 1 case, and the marginal necrosis of the abdominal flap after operation occurred in 1 case. The remaining fingers showed good blood supply with normal tension. The incision at donor site of the abdominal flap healed by first intention. All patients were followed up 8-41 months (median, 19 months). At last follow-up, the hand contour was satisfactory; the grasping function, opposition function, and proprioception recovered, and two-point discrimination ranged from 5 to 7 mm (mean, 6 mm). According to the upper extremity function evaluation criteria issued by Hand Surgery Society of the Chinese Medical Association, the functional outcomes were excellent in 3 cases, good in 1 case, and fair in 1 case. CONCLUSION The multi-segment inverted Y-shaped vein transplantation using the anterior lateral malleolar venous network for repairing defects in the common and proper palmar digital arteries distal to the superficial palmar arch offers advantages such as superficial location, flexible harvesting, and high compatibility. This technique has demonstrated favorable outcomes in complex transmetacarpal amputation reconstruction.
Humans ; Adult ; Male ; Female ; Hand Injuries/surgery* ; Middle Aged ; Plastic Surgery Procedures/methods* ; Veins/transplantation* ; Surgical Flaps/blood supply* ; Hand/surgery* ; Treatment Outcome ; Soft Tissue Injuries/surgery*

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Candidiasis has a high morbidity and mortality worldwide,and its main causative agent is Candi-da albicans.At present,the treatment effect of candidiasis is not ideal due to the shortcomings of antifungal drugs,such as toxicity,drug resistance,single route of administration,and high price.In order to overcome this situation,metal nanoparticles with antifungal activity and the potential to deliver antifungal drugs have been extensively studied.In this paper,the mechanism and application of gold,silver,copper and iron nanoparticles against Candida albicans are reviewed.Compared with traditional antifungal drugs,metal nanoparticles exert antifungal effects through a multi-target mechanism,which minimizes the emergence of antifungal resistance.Cytotoxicity limits the application of metal nanoparticles,but green synthesis can reduce the cytotoxicity of metal nanoparticles and improve antimicrobial properties.

Objective To evaluate the effect of manual massage on complications after endoscopic foam sclerotherapy injection for the treatment of internal hemorrhoids.Methods Consecutive 113 patients with grade Ⅰinternal hemorrhoids were prospectively enrolled and completed endoscopic foam sclerotherapy.The patients were randomly divided into a massage group(n=65)and a control group(n=68).Massage group performed manual perianal massage,Visual analogue scale(VAS)was used to evaluate perianal pain.The postoperative bleeding,short-term and long-term efficacy were also compared.Results The median VAS of 24 h postoperation was 1.0(0.0,3.0)in massage group,which was significantly lower than 2.0(1.0,4.0)in control group,the difference was statistically significant(P=0.014).The no bleeding rate of one week postoperation was 84.6％in massage group,which was significantly higher than 64.7％in control group,the difference was statistically significant(P=0.009).After 12 weeks,6 months and 12 months of follow-up,there were no significant differences in cure rate and remission rate between the two groups(P＞0.05).Conclusion Manual massage after endoscopic sclerosing agent injection is beneficial to relieve postoperative pain of grade Ⅰ internal hemorrhoids and reduce bleeding.

Objective:To investigate the expression and clinical significance of CD30 in patients with diffuse large B-cell lymphoma(DLBCL).Methods:A retrospective analysis was conducted on 124 cases of primary DLBCL diagnosed at Changzhou Second People's Hospital Affiliated with Nanjing Medical University from January 2018 to July 2020.The expression of CD30 in patients with DLBCL was detected by immunohistochemical method,and the clinicopathological characteristics were analyzed and compared between CD30+and CD30-groups.Kaplan-Meier analysis was used for survival analysis.The relationship between CD30 expression and clinical features and prognosis were analyzed.Results:Among the 124 patients with DLBCL,19 patients expressed CD30,and the positive rate is 15.32％.The clinico-pathological characteristics of CD30+in patients with DLBCL were characterized by low age,more common in males,fewer extranodal lesions,lower international prognostic index(IPI),GCB type being more common in Hans subtype,and achieving better therapeutic effects(P＜0.05).However,there were no significant statistical differences in B-symptoms(P=0.323),Ann Arbor staging(P=0.197),Eastern Cooperative Oncology Group(ECOG)score(P=0.479),lactate dehydrogenase(LDH)(P=0.477),and the involvement of bone marrow(P=0.222).There were significant differences in OS and PFS between the CD30+and CD30-groups(x2=5.653,P=0.017;x2=4.109,P=0.043),the CD30+group had a better prognosis than that of the CD30-group.The results of subgroup analysis showed that the CD30+group in the IPI score=1-2,LDH elevated group had a better prognosis(P＜0.05).In the subgroups of Ann Arbor staging Ⅲ-Ⅳ(P=0.055)and non GCB type(P=0.053),the CD30+group had a good prognosis trend,but the difference was not statistically significant.The results of univariate analysis showed that the good prognosis of DLBCL patients was closely related to CD30+expression,no B-symptoms,early Ann Arbor staging,low ECOG score,normal LDH,low IPI score,fewer extranodal involvement,and obtaining the best therapeutic effect as CR(all P＜0.05).COX multivariate regression analysis showed that the presence of B-symptoms and achieving the best therapeutic effect as Non-CR were independent risk factors affecting the prognosis of DLBCL patients(P＜0.05).Conclusion:The CD30+expression in DLBCL patients indicates a good prognosis and has certain diagnostic value in evaluating the prognosis of DLBCL patients.

Objective To explore the magnetic resonance imaging(MRI)manifestations of acute cerebral infarction(ACI)and the correlation between lipoprotein-associated phospholipase A2(Lp-PLA2),cystatin C(Cys C)and short-term prognosis.Methods A total of 110 ACI patients admitted to the department of neurology in our hospital from January 1,2022 to January 1,2023 were selected as the study objects.The clinical data and multimodal MRI were collected,and the serum Lp-PLA2 and Cys C levels of patients were detected.The patients were divided into the good prognosis group and the poor prognosis group according to the modified Rankin scale(mRS)score 90 days after onset.The predictive value of MRI manifestations and Lp-PLA2 and Cys C levels for short-term poor prognosis was analyzed.Results There were statistically significant differences in the time from onset to admission,National Institute of Health Stroke Scale(NIHSS)score on admission,hypertension or diabetes,coronary heart disease or atrial fibrillation of patients between the good prognosis group and the poor prognosis group(P<0.05).The proportions of patients with ischemic penumbra,HV positive,cortical-subcortical infarction,large perforating branch infarction,small perforating branch infarction,bilateral anterior circulation infarction,posterior circulation infarction,anterior-posterior circulation infarction,middle cerebral artery(MCA)stenosis or occlusion,both internal carotid artery(ICA)and MCA stenosis or occlusion,posterior cerebral artery(PCA)or vertebral artery(VA)stenosis or occlusion and hemorrhage transformation in the poor prognosis group were significantly higher than those in the good prognosis group(P<0.05).The Lp-PLA2 and Cys C levels of patients in the poor prognosis group were significantly higher than those in the good prognosis group(P<0.05).Small penetrating branch infarction,posterior circulation infarction,anterior-posterior circulation infarction,MCA stenosis or occlusion,both ICA and MCA stenosis or occlusion,hemorrhage transformation,serum Lp-PLA2 and Cys C had certain predictive value for patients with short-term poor prognosis(P<0.05).Conclusion MRI manifestations(ischemic penumbra,HV positivity,different types of cerebral infarction,and vascular stenosis)and serum Lp-PLA2 and Cys C levels can predict the short-term prognosis of ACI patients and provide important reference for the formulation of clinical treatment plans.