Purpose: This study aimed to evaluate the impact of postoperative adjuvant chemotherapy (AC) on survival outcomes in breast cancer (BC) patients who have already undergone neoadjuvant chemotherapy (NAC) followed by surgery. Materials and Methods: Data from a population-based cohort (2010-2020) were analyzed for BC patients treated with NAC and surgery. Univariate and multivariate Cox regression identified prognostic factors for overall survival (OS), and a nomogram was developed and validated. Personalized scores from the nomogram were used for risk stratification to assess the effect of postoperative AC. Results: A total of 15,921 BC patients were analyzed, with 11,144 in the training cohort and 4,777 in the validation cohort. The key prognostic indicators for OS included age, race, marital status, histological grade, BC subtype, T category, N category, type of surgery, and response to NAC (all p < 0.05). The nomogram effectively predicted individualized OS rates and stratified patients into various risk categories. Postoperative AC was found to significantly enhance OS in the high-risk subgroup (p=0.011 in the training cohort, p=0.012 in the overall population). However, for the low-risk subgroup, there was no significant survival benefit from postoperative AC (p=0.130 for the training cohort, p=0.588 for the overall population), suggesting that some patients might safely forgo unnecessary postoperative AC. Conclusion This study efficiently differentiates between varying levels of risk, enabling clinicians to identify patients unlikely to benefit from postoperative AC and thus reduce the likelihood of overtreatment.

ObjectiveTo systematically analyze the global policy framework, standard systems and application technology models of digital rehabilitation within the framework of the World Health Organization (WHO) Global Digital Health Strategy and propose policy recommendations for the future development of digital rehabilitation. MethodsBased on the policies on digital health and rehabilitation development issued by the WHO, focusing on the Global Digital Health Strategy, Rehabilitation 2030 Initiative, Rehabilitation in Health Systems, Rehabilitation in Health Systems: A Guide for Action, and World Report on Disability, a systematic review was conducted, to explore the policy architecture and core content of digital rehabilitation, the standard system for digitalizing rehabilitation, and key technological models for the development of digital rehabilitation. ResultsIn the context of global health and digital transformation, the development of digital rehabilitation services was an essential component of the global digital health strategy. Building a comprehensive policy framework and content system for digital rehabilitation was critical for strengthening rehabilitation data governance, enhancing data utilization efficiency, and ensuring data privacy and security. Empowering rehabilitation with digital technology was vital for improving the standardization, effectiveness, coverage, quality and safety of rehabilitation services. International digital rehabilitation policies primarily involved the following areas: policy and governance, digital standard systems, data privacy, security and ethics, digital talent cultivation and capacity building, and monitoring, evaluation and continuous improvement of digitally empowered rehabilitation services. The standard system for rehabilitation digitization covered the three major reference classifications of the WHO Family of International Classifications, including International Classification of Diseases Eleventh Revision (ICD-11), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Interventions (ICHI), especially ICF. It also included international data interoperability standards, data security and privacy protection standards, data quality and certification standards, and health information standards, etc. The application technology models of digital rehabilitation primarily included data-driven service models, artificial intelligence -enabled models, and remote rehabilitation models combined with virtual reality, augmented reality technologies, and Internet of Things support. ConclusionThe establishment and implementation of comprehensive policies, standards and technological models for digital rehabilitation are crucial for driving the digital transformation and development of global rehabilitation services. Under the framework of the WHO Global Digital Health Strategy, it is necessary to build adaptive digital rehabilitation policy frameworks, and enhance digital governance capabilities and levels, establishing and improving digital rehabilitation standard systems, and promoting the interoperability and integration of rehabilitation data with other health big data. Meanwhile, it is essential to actively develop data-driven technological models for rehabilitation services to comprehensively improve the accessibility, availability, quality and safety of rehabilitation services.

Objective To investigate the impact of two different surgical methods, orthotopic kidney transplantation and abdominal heterotopic kidney transplantation, on the surgical outcomes of pig-to-pig kidney transplantation and the short-term survival of recipient pigs after surgery. Methods Twenty-four Bama miniature pigs were divided into two groups, with 12 pigs in each group, and underwent orthotopic kidney transplantation and abdominal heterotopic kidney transplantation, respectively. The perioperative indicators of the recipient pigs, renal blood perfusion, the overall incidence rate of complications and survival rate were compared between the two surgical methods. Results The total surgical time, renal artery anastomosis time, renal vein anastomosis time, cold ischemia time and total ischemia time were all shorter in the abdominal heterotopic kidney transplantation group than in the orthotopic kidney transplantation group, with statistically significant differences (all P<0.05). The number of satisfactory renal perfusion cases was higher in the abdominal heterotopic kidney transplantation group than in the orthotopic kidney transplantation group (83% vs. 75%), but the difference was not statistically significant (P>0.05). The total incidence of postoperative complications was 33% in the heterotopic kidney transplantation group, with a survival rate of 92%, and the cause of death was rupture of the vascular anastomosis. The total incidence of postoperative complications was 50% in the orthotopic kidney transplantation group, with a survival rate of 83%, and the causes of death were renal vein thrombosis and renal artery thrombosis. There were no statistically significant differences in the total incidence of postoperative complications and survival rates between the two groups (all P>0.05). Conclusions Compared with orthotopic kidney transplantation, abdominal heterotopic kidney transplantation showes better surgical outcomes in pig-to-pig kidney transplantation and is more beneficial for the short-term survival of recipient pigs after surgery. This provides experience for improving the stability of pig-to-non-human primate kidney xenotransplantation models in the future.

Objective: To investigate the biological effects of carvacrol on rats with stomach-heat and stomach-cold and its regulation on transient receptor potential(TRP) channels in rats with stomach-heat, and to study the cold and heat properties of carvacrol and its possible mechanism. Methods: According to the random number method, 100 SD rats were divided into stomach-heat blank group, stomach-heat model group, Coptidis Rhizoma group, stomach-heat low-dose and high-dose carvacrol group, stomach-cold blank group, stomach-cold model group, Baked ginger group, stomach-cold low-dose group and high-dose carvacrol group, 10 rats in each group. The rat model of stomach-heat was established by intragastric administration of pepper aqueous solution (0.80 g/kg) and anhydrous ethanol, and the rat model of stomach-cold was established by intragastric administration of water extract of Anemarrhena asphodeloides and sodium hydroxide (10.40 g/kg). On the day of modeling, the rats in the Baked ginger group were given Baked ginger decoction (0.78 g/kg), and the rats in the Coptidis Rhizoma group were given Coptidis Rhizoma decoction (0.43 g/kg).The stomach-cold and stomach-heat low-dose group of carvacrol was given carvacrol emulsion (40 mg/kg), high-dose group was given carvacrol emulsion (80 mg/kg).All rats of the blank and model groups were given the equal volume of emulsion prepared by 5% dimethyl sulfoxide, 1% Tween 80, 1% polyethylene glycol 400, and 93% normal saline, once a day, for 7 days. The general condition of rats was observed and the body mass was recorded. The pathological morphology of gastric tissue was observed by hematoxylin-eosin staining. The changes of material and energy metabolism, cyclic nucleotide (cAMP), thyroid hormone and gastrointestinal hormone in each group were determined by enzyme-linked immunosorbent assay. The expression levels of transient receptor potential vanilloid subtype 1 (TRPV1), transient receptor potential channel M8 (TRPM8) and uncoupling protein-1 (UCP1) in rats with gastric fever were detected by Western blotting. Results: Compared with the stomach-heat blank group, the body mass of rats in the stomach-heat model group decreased at the fifth and seventh day (P<0.05). The contents (or ratio) of hepatic glycogen (HGlyc), total cholesterol (TC), triglyceride (TG), and vasoactive intestinal peptide (VIP) were decreased (P<0.05), and Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, cytochrome C oxidase (COX), NADH dehydrogenase (ND), cyclic adenosine phosphate (cAMP), cAMP/cyclic guanosine phosphate (cGMP), triiodothyronine (T3), thyroxine (T4), gastrin (GAS), motilin (MTL), and α-amylase (α-AMS) all increased (P<0.05). Compared with the stomach-heat model group, the body mass of rats in the Coptidis Rhizoma group decreased at the third, fifth, and seventh day, the contents (or ratio) of HGlyc, TC, TG, VIP and α-AMS were increased, and Na+ -K+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, and GAS all decreased (P<0.05). The body mass of rats in the stomach-heat low-dose carvacrol group decreased at the seventh day. The contents (or ratio) of HGlyc, TC, and VIP were increased, Na+ -K+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, and MTL all decreased, the expression of TRPV1 and UCP1 in gastric tissue decreased, while TRPM8 increased (P<0.05) in rats of the stomach-heat low-dose and high-dose carvacrol groups. Compared with the stomach-cold blank group, the body mass of rats in the stomach-cold model group decreased at the third, fifth, and seventh day, the contents (or ratio) of HGlyc, TC, TG, α-AMS, and VIP all increased, while Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, GAS, and MTL all decreased (P<0.05). Compared with the stomach-cold model group, the body mass of rats in the Baked ginger group was increased at the seventh day, and the contents (or ratio) of HGlyc, VIP, and α-AMS all decreased, while Na+ -K+ -ATPase, COX, ND, cAMP/cGMP, T3, T4, GAS, and MTL all increased (P<0.05). The contents of HGlyc, cAMP, α-AMS, and VIP of rats in the stomach-cold low and high-dose carvacrol group all decreased (P<0.05). TG in the stomach-cold low-dose carvacrol group was increased. TC, Ca2+ -Mg2+ -ATPase, and cGMP all increased, while cAMP/cGMP decreased (P<0.05) in the high-dose carvacrol group. Conclusion In this study, the rat model of stomach-cold and stomach-heat were successfully established by using cold and heat factors. The result showed that carvacrol had a certain inhibitory effect on body mass, material energy metabolism, cyclic nucleotide level, thyroid hormone and gastrointestinal function in rats with stomach-heat, indicating that the drug was cold. Carvacrol′s cold medicinal property could be biologically explained by TRPV1 activation, UCP1 induction, and TRPM8 suppression.

Background: The genus Atractylodes, native to East Asia, encompasses several species that serve as sources for the widely used traditional Chinese medicines Atractylodis Macrocephalae Rhizoma and Atractylodis Rhizoma. However, the international trade arouses concern regarding potential confusion and misidentification of Atractylodes species. Objective: A comprehensive understanding of the chemical diversity is crucial for ensuring the quality and exploring the potential variations in medicinal efficacy of Atractylodes. Methods: The GC-MS/MS-based metabolomics and multivariate statistical analysis identified 589 differentially accumulated metabolites across 5 Atractylodes species. Results: A total of 150 metabolites were predicted as potential chemical markers for species differentiation and quality assessment of Atractylodes. According to the metabolic profiles, the species of Atractylodes can be roughly classified into three categories: A. lancea and A. coreana with the volatile oil components being mainly atractylodin and β-eudesmol; A. macrocephala with the biomarker being atractylon; and A. japonica and A. carlinoides lying between the two categories above. Conclusions: Metabolomic results indicated that the metabolic profiles of A. carlinoides and A. macrocephala were similar and distinct from those of the other three species. Sesquiterpenoids were the main chemical components in the rhizome of A. carlinoides, which indicated the potential medicinal value of this plant.

Background: The genus Atractylodes, native to East Asia, encompasses several species that serve as sources for the widely used traditional Chinese medicines Atractylodis Macrocephalae Rhizoma and Atractylodis Rhizoma. However, the international trade arouses concern regarding potential confusion and misidentification of Atractylodes species. Objective: A comprehensive understanding of the chemical diversity is crucial for ensuring the quality and exploring the potential variations in medicinal efficacy of Atractylodes. Methods: The GC-MS/MS-based metabolomics and multivariate statistical analysis identified 589 differentially accumulated metabolites across 5 Atractylodes species. Results: A total of 150 metabolites were predicted as potential chemical markers for species differentiation and quality assessment of Atractylodes. According to the metabolic profiles, the species of Atractylodes can be roughly classified into three categories: A. lancea and A. coreana with the volatile oil components being mainly atractylodin and β-eudesmol; A. macrocephala with the biomarker being atractylon; and A. japonica and A. carlinoides lying between the two categories above. Conclusions: Metabolomic results indicated that the metabolic profiles of A. carlinoides and A. macrocephala were similar and distinct from those of the other three species. Sesquiterpenoids were the main chemical components in the rhizome of A. carlinoides, which indicated the potential medicinal value of this plant.

Background: The genus Atractylodes, native to East Asia, encompasses several species that serve as sources for the widely used traditional Chinese medicines Atractylodis Macrocephalae Rhizoma and Atractylodis Rhizoma. However, the international trade arouses concern regarding potential confusion and misidentification of Atractylodes species. Objective: A comprehensive understanding of the chemical diversity is crucial for ensuring the quality and exploring the potential variations in medicinal efficacy of Atractylodes. Methods: The GC-MS/MS-based metabolomics and multivariate statistical analysis identified 589 differentially accumulated metabolites across 5 Atractylodes species. Results: A total of 150 metabolites were predicted as potential chemical markers for species differentiation and quality assessment of Atractylodes. According to the metabolic profiles, the species of Atractylodes can be roughly classified into three categories: A. lancea and A. coreana with the volatile oil components being mainly atractylodin and β-eudesmol; A. macrocephala with the biomarker being atractylon; and A. japonica and A. carlinoides lying between the two categories above. Conclusions: Metabolomic results indicated that the metabolic profiles of A. carlinoides and A. macrocephala were similar and distinct from those of the other three species. Sesquiterpenoids were the main chemical components in the rhizome of A. carlinoides, which indicated the potential medicinal value of this plant.

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

Traditional Chinese medicine(TCM) resources are an important foundation for the theory and practice of TCM. Rare and endangered TCM, as a significant component of these resources, plays an essential role. Conducting research on substitutes for rare and endangered TCM resources is of great significance for alleviating resource shortages, promoting the sustainable utilization of TCM, and advancing TCM modernization. This paper reviews the conservation achievements of rare and endangered Chinese medicinal materials in China and organizes the substitution methods for these materials. Currently, the main substitution approaches include introduction and domestication, tissue culture, varietal replacement, and artificial synthesis. Furthermore, this paper proposes the following approaches for researching the application scenarios of rare and endangered medicinal materials, i.e., tracing the historical context of their use to clarify foundational principles; verifying disease classifications to strengthen the clinical application scenarios of these materials; analyzing the evolution patterns of prescription formulations to strengthen the mining of the compatibility application scenarios of rare and endangered medicinal materials; scientifically evaluating to strengthen the application scenario research and development of endangered Chinese patent medicine industry. These efforts aim to promote the scientific substitution and sustainable utilization of rare and endangered medicinal materials and their substitutes.
Drugs, Chinese Herbal/chemistry* ; Humans ; Medicine, Chinese Traditional ; China ; Plants, Medicinal/growth & development* ; Endangered Species ; Conservation of Natural Resources ; Animals

Laccase is a type of polyphenol oxidase that can catalyze the oxidation of various substances,including phenols,aromatic amines,and catecholamines.It has been widely utilized in pollutant degradation and analytical applications.However,the high cost of preparation of natural laccase and its susceptibility to environmental factors,which can lead to denaturation and inactivation,limit its practical applications.Nanozymes,which are nanomaterials that exhibit enzyme-like properties,offer advantages such as easy preparation,adjustable activity,and exceptional stability.Currently,many types of nanozymes have been developed.Inspired by the coordination of Cu2+with amino acids in the active site of natural laccase,researchers have employed coordination synthetic strategies to prepare laccase-like nanozymes.The metal nodes in these laccase-like nanozymes include copper,manganese,and cerium,while the ligands involve a variety of chemicals like nucleotides,amino acids,polypeptides,and aromatic acids.By manipulating factors such as the metal-to-ligand ratio,reducing capacity of ligands,buffer solutions,chloride ions,bromine ions,the catalytic activity of laccase-like nanozymes can be finely tuned.In this paper,laccase-like nanozymes developed through coordination strategies were categorized and summarized,along with review of their analytical applications in detection of phenolic compounds,disease biomarkers,antibiotics,pesticides,sulfur-containing pollutants,and time-temperature indicators.Furthermore,the challenges currently faced in the research of laccase-like nanozymes and future research directions were discussed.