Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Laccases (LACs), belonging to the multicopper oxidase family, are closely associated with various biological functions including lignin synthesis and responses to biotic and abiotic stresses in plants. However, few studies have reported the laccase genes in China rose (Rosa chinensis). Prickles cause difficulties to the management and harvest of R. chinensis and have become a trait concerned in the breeding. To investigate the expression patterns of laccase genes in roses, we cloned a laccase gene from an ancient variety R. chinensis 'Old Blush' and named it RcLAC15. The expression level of RcLAC15 in prickles was significantly higher than those in roots, stems, and leaves. Fifty-eight laccase genes were identified in the genome of R. chinensis, and bioinformatics analysis revealed that RcLAC15 was a homolog of AtLAC15, predicting that RcLAC15 was a stable hydrophilic protein without transmembrane structures. The recombinant expression vector pBI121-proRcLAC15:: GUS was introduced into Arabidopsis, and GUS staining results showed that the RcLAC15 promoter specifically drove GUS gene expression at the edges of Arabidopsis leaves. In summary, RcLAC15 is a gene specifically expressed in the prickles of R. chinensis. This discovery provides a reference for exploring the biological functions of laccase genes in the prickles of R. chinensis.
Laccase/metabolism* ; Rosa/enzymology* ; Cloning, Molecular ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Arabidopsis/metabolism* ; Plants, Genetically Modified/metabolism*

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

Objective To explore the efficacy and safety of dapagliflozin in patients with paroxysmal atrial fibrillation (PAF) combined with heart failure with preserved ejection fraction (HFpEF). Methods A total of 120 patients with PAF combined with HFpEF treated at Jinshan Hospital of Fudan University from July 2022 to July 2023 were selected and randomly divided into the dapagliflozin group (n＝60, standard treatment combined with dapagliflozin) and the control group (n＝60, standard treatment combined with placebo). After 12 months of follow-up, the Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS), PAF duration, recurrence rate and frequency of PAF, left atrial diameter, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left ventricular ejection fraction, P-wave dispersion, blood pressure, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP), estimated glomerular filtration rate (eGFR), and glycated hemoglobin A_1C (HbA_1C) were compared between the two groups. Cardiovascular outcomes and adverse events were observed. Results A total of 10 patients lost to follow-up, and 110 patients were included in the analysis (55 in each group). After 12 months of treatment, the KCCQ-TSS in the dapagliflozin group was significantly higher than that in the control group ([61.68±2.65] points vs [44.98±4.76] points, P＜0.001). The PAF duration in the dapagliflozin group was significantly shorter than that in the control group ([144±18] min vs [270±24] min, P＝0.045). After treatment, frequency of PAF, NT-proBNP levels, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left atrial diameter, P-wave dispersion, and HbA_1C levels showed statistical differences between the two groups (P＜0.05). The heart failure readmission rate and PAF recurrence rate in the dapagliflozin group were significantly lower than those in the control group (P＜0.05). There was no significant difference in the incidence of adverse events between the two groups during treatment. Conclusions Dapagliflozin improves patients’ quality of life, reduces PAF duration and recurrence rate, decreases heart failure readmission rate, lowers NT-proBNP levels, reverses cardiac remodeling, and demonstrates favorable safety in patients with PAF combined with HFpEF.

To further standardize the management of vaccination units, the Specifications for Vaccination (2023 version) proposes hierarchical management. However, guidelines for establishing, implementing, and evaluating such a framework remain underdeveloped. This paper systematically reviews the current status of hierarchical management in vaccination units, clarifies its feasibility and necessity, and proposes an implementation scheme.

Objective:To observe the characteristics of gastrointestinal tract symptoms in patients with Parkinson′s disease (PD) and analyze the characteristics of these symptoms in patients with different PD subtypes.Methods:A total of 297 PD patients who were admitted to the Neurology Department of the Second Affiliated Hospital of Soochow University from November 2022 to March 2024 were enrolled. The gastrointestinal symptoms of PD patients were evaluated using Drooling Severity and Frequency Scale (DSFS), Sialorrhea Clinical Scale for Parkinson′s disease (SCS-PD), Drooling Rating Scale (DRS), Eating Assessment Tool 10 (EAT-10), Gastroparesis Cardinal Symptom Index (GCSI), and Rome Ⅳ diagnostic criteria. The patients were grouped based on the presence or absence of gastrointestinal symptoms. Additionally, they were stratified according to disease duration (≤2 years, 2-5 years, 5-10 years, and>10 years) and motor symptom subtype [tremor-dominant (TD) vs. postural instability and gait difficulty (PIGD)]. One-way ANOVA and logistic regression analysis were applied to examine between-group differences while Spearman correlation analysis was employed to assess correlations between clinical symptoms.Results:The average age of the patients with PD was 67.0 (60.0, 72.0) years, and 161 (54.2%) were male. The incidence of PD combined with gastrointestinal symptoms was, in descending order: constipation (191, 64.3%), salivation (155, 52.2%), gastroparesis (93, 31.3%), and dysphagia (68, 22.9%). Compared with PD patients without gastrointestinal symptoms, those with symptoms had higher scores in the RBD-HK [12.0 (5.0, 21.5) vs. 5.0 (0.0, 9.0), Z=-3.74, P=0.017], ESS [6.0 (2.0, 12.0) vs. 3.0 (0.0, 6.0), Z=-3.20, P=0.023], and MDS-UPDRS Part Ⅰ [9.0 (5.0, 14.0) vs. 5.0 (2.3, 9.0), Z=-3.61, P=0.014]. The severity of sialorrhea and deglutition disorders, along with the incidence of constipation, all increased with longer disease duration. Patients with the PIGD subtype had higher GCSI scores than those with the TD subtype [0.0 (0.0, 1.9) vs. 0.0 (0.0, 0.0), Z=-3.57, P=0.007]. Across the cohort, sialorrhea, deglutition disorders, gastroparesis, and constipation were positively associated with the H-Y stage, MDS-UPDRS Ⅰ, HAMD, NMSQ, and SCOPA-AUT; EAT-10 scores were negatively correlated with MoCA ( r=-0.171, P<0.05); and GCSI scores were negatively correlated with MMSE and MoCA ( r=-0.154, r=-0.169, both P<0.05). Conclusions:Overall, 84.5% of the patients with PD had one or more gastrointestinal symptoms, and the incidence and severity of gastrointestinal symptoms increased with disease duration. The severity of gastroparesis was higher in the PIGD group than in the TD group. The scores of all gastrointestinal symptoms were positively correlated with the H-Y stage and MDS-UPDRS Ⅰ, while the GCSI scores were negatively correlated with the cognitive scores.

The emergence of generative pre-training transformer(GPT)and large language models(LLMs)has brought transformative applications to the medical field.In traditional Chinese medicine,LLMs offer unique opportunities to address in efficiencies in clinical workflows and improve the patient experience.However,the seprospects have challenges,including data quality,security and privacy,disinformation,ethics,and other issues.This paper systematically elaborates on the application of Large Language Models(LLMs)in Traditional Chinese Medicine(TCM),highlighting their value in improving TCM services,enhancing teaching effectiveness,and optimizing healthcare management processes,while conducting an in-depth analysis of potential technical and ethical challenges during real-world implementation.Preventive measures are necessary to ensure the safe and unbiased use of large language models in TCM clinical practice.We encourage clinicians and researchers to address current challenges and optimize largelanguage models while reducing associated risks.The deployment and implementation of large language models in TCM clinical practice will significantly contribute to the dissemination and development of TCM culture.

Olfactory diagnosis refers to the method of diagnosing diseases by smelling the odor emitted from the patient's body,secretions and excreta,and the odor of the sick room.It is one of the important diagnostic methods under the guidance of traditional Chinese medicine(TCM)theory,and is included in the"inquiry and olfaction"of TCM.In recent years,there has been rapid development in medical-engineering integration,artificial intelligence,big data,and other interdisciplinary fields.This has been promoting the TCM gradually to develop towards accurate,efficient and personalized medical treatment,which has opened a new era of"Smart TCM".In this paper,the ancient literature related to olfactory diagnosis was systematically reviewed,the developmental characteristics of olfactory diagnosis theories in various periods was sorted out,and the different views of TCM specialists on the odors emitted by the human body in physiological and pathological states was summarized.The paper is to explore the origin of TCM olfactory diagnosis and its periodization,clarify the diagnosis of abnormal odors,corresponding to the nature,etiology and prognosis of the disease,and clarify the development of TCM olfactory diagnosis.It provides a theoretical source and literature basis for promoting the research of"smart olfactory diagnosis of TCM"and facilitating the development of objectivity,standardization and intelligence of olfactory diagnosis in TCM.

Objective The myocardial injury was induced by hypobaric hypoxia through regulating the expression of various proteins.The expression of proteins was mainly detected by western blot,but the selection of internal reference proteins and their variations have not been systematically studied.Methods Myocardial injury was induced in a low-pressure,low-oxygen chamber simulating an altitude of 6000 m,for 24 and 72 h.Establishment of the myocardial injury model was confirmed by hematoxylin eosin(HE)staining.Expression levels of internal control proteins,including vinculin,α-tubulin,eukaryotic translation initiation factor-5(EIF5),β-actin,glyceraldehyde-3-phosphate dehydrogenase(GAPDH),cyclophilin B,and cofilin,were detected by Western Blot and total protein expression was detected by Ponceau S and Coomassie Blue staining.An adult mouse cardiomyocytes(AMCMs)injury model was induced by hypoxia for 12 and 24 h and confirmed by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL staining).Internal control proteins were detected by Western Blot,as in the in vivo model,and total protein expression was detected by Ponceau S and Coomassie Blue staining.Results A myocardial injury model was established by hypobaric hypoxia for 24 and 72 h,the total protein expression levels remained consistent.The expression of internal control proteins including vinculin,EIF5,β-actin,cyclophilin B,and cofilin was consistent between the control and model groups.Expression levels of α-tubulin were similar in the plain control and 24 h hypobaric hypoxia group,but were significantly lower in the 72 h hypobaric hypoxia group compared with the plain control group.GAPDH expression was significantly higher in the 24 and 72 h hypobaric hypoxia groups than in the plain control group.An AMCM injury model was established by hypoxia for 12 and 24 h.Total protein levels and expression levels of the internal control proteins EIF5 and β-actin were consistent,but vinculin,α-tubulin,GAPDH,cyclophilin B,and cofilin expression levels were higher in both hypoxia groups compared with the normoxic control group.Conclusions EIF5 and β-actin may be the suitable loading control proteins for studies of hypobaric hypoxia-induced myocardial injury using Western Blot.Total protein is also a good choice for hypobaric hypoxia studies.