Objective To analyze the epidemiological characteristics of norovirus outbreaks in Haidian District, Beijing, and to provide a reference for epidemic prevention and control. Methods Descriptive epidemiological methods were used to organize and statistically analyze the norovirus outbreak data reported from 2016 to 2022. Results A total of 26 outbreaks of norovirus were reported in Haidian District, with a total of 1595 cases and an attack rate M (Q_R) of 8.23 (16.33)%. There were 24 cases of norovirus type GII (92.31%), 1 case of type GI (3.85%), and 1 case of mixed infection of virus type GI/GII (3.85%). The highest number of reported outbreaks occurred in March and April, with 17 cases, accounting for 65.38%. The highest number of reported cases was in November and December, with 785 cases, accounting for 44.92%. The case age M (Q_R) was 18 (14) years old. The detection rate of positive samples in different age groups had statistical significance（χ²=12.021, P=0.007). The 26 outbreaks were mainly distributed in collective units such as schools, preschool institutions, and enterprises and institutions. There were a total of 11 outbreaks related to foodborne transmission, with 923 cases, accounting for 57.87%. Diarrhea was positively correlated with the age of the cases (r_s=0.572, P<0.001), while vomiting was negatively correlated with the age of the cases (r_s=-0187, P<0.001). The time interval between the onset of acute gastroenteritis symptoms in the first case and the reporting of the epidemic was positively correlated with the duration of the epidemic (r_s=0.586, P=0.002). Conclusion It is necessary to strengthen the prevention and control of norovirus in schools (primary and secondary schools and colleges), strictly implement health monitoring and regular screening for kitchen workers, carry out publicity and education, detect cases as early as possible, report the epidemic in a timely manner, and effectively reduce the scale of the epidemic and prevent its spread.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

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.

Myelodysplastic syndrome (MDS), a myeloid tumor derived from the malignant clones of hematopoietic stem cells, has an annually increasing incidence. The contemporary research direction has shifted to analyzing the synergistic effect of immune surveillance collapse and abnormal bone marrow microenvironment in the pathological process of MDS. Against this backdrop, the immune checkpoint molecule TIM3 has emerged as a key target because of its persistently high expression on the surface of important immune cells such as T and NK cells. The abnormal activation of the TIM3 pathway is the mechanism by which solid tumors and hematological malignancies achieve immune escape and is a key hub in the formation of immune exhaustion phenotypes. This work integrates the original discoveries of our team with the latest international progress, systematically demonstrating the bidirectional regulatory network of TIM3 between the malignant clone proliferation of MDS and the immunosuppressive microenvironment. Integrating the evidence from emerging clinical trials allows us to consider the clinical significance of TIM3-targeted blocking for MDS, providing a transformative path to overcome the resistance of traditional treatments and marking a new chapter in the active immune reconstitution of MDS treatment.

Mendel established the laws and laid the foundation of modern genetics through his famous hybridization experiments on seven pairs of classic traits in the garden pea (Pisum sativum). However, the molecular bases underlying these traits have only come into sharp focus in recent years. Leveraging advances in traditional map-based cloning, TILLING, long-read resequencing, population genetics, and GWAS, this article synthesizes current knowledge of ten genes governing seven traits—plant height, seed shape, flower color, seed color, pod color, pod morphology, and flower position—by summarizing each gene’s identity, chromosomal localization, and functional pathway. For plant height, the classical Le locus corresponds to PsGA3ox1, which encodes a gibberellin 3β-hydroxylase. Mutations at Le impede the biosynthesis of the bioactive hormone GA₁, and the resulting deficiency leads to a dwarf or reduced-stature phenotype. Seed shape is determined by R, identified as PsSBEI (starch-branching enzyme I). Insertion of a transposable element into R restricts amylopectin synthesis, perturbing endosperm starch architecture and resulting in the wrinkled seeds noted by Mendel. Flower color is specified by the coordinated action of A (a bHLH transcription factor) and A2 (a WD40 scaffold). Together, they assemble the canonical MYB-bHLH-WD40 (MBW) regulatory complex, which co-activates structural genes in the anthocyanin pathway to determine pigment accumulation and floral hue. Seed color is governed by I, which encodes PsSGR (STAY-GREEN), a magnesium dechelatase that catalyzes a key step in chlorophyll catabolism. Loss-of-function alleles at I block chlorophyll degradation, yielding “stay-green” seeds in which chlorophyll persists beyond normal developmental stages. Pod coloration maps to Gp, corresponding to ChlG (chlorophyll synthase). Either direct loss of ChlG function or readthrough-fusion transcriptional interference caused by a large upstream deletion suppresses chlorophyll biosynthesis in developing pods, resulting in the yellow-pod phenotype. Pod morphology depends on two convergent regulatory pathways. The P gene, PsCLE41, signals through the P-PXY-WOX/NAC axis to promote vascular differentiation and secondary-wall programs, while V encodes PsMYB26, a transcription factor that drives secondary wall thickening in fiber cells. Acting in concert, these modules ensure robust secondary-wall deposition in the fiber layer lining the inner pod wall; disruption of either component compromises wall thickening and leads to pleated or wrinkled pods. Flower position (inflorescence determinacy at the shoot apex) is controlled by FA, identified as PsCIK, which participates in the CLAVATA-WUSCHEL (CLV-WUS) feedback circuit that maintains shoot apical meristem homeostasis. Mutations in FA destabilize this self-regulatory loop and promote terminal flowers at the apex. The expressivity of this determinacy phenotype is further modulated by a recessive modifier, Mfa, which fine-tunes the outcome in the fa background. Across these loci, convergent evidence highlights the central role of structural variation in generating the classical Mendelian phenotypes. Building on this clarified molecular landscape, we outline practical implications for quality improvement and the deliberate “design” of traits. Looking ahead, we envisage a next generation of legume genetic improvement anchored on three mutually reinforcing pillars: high-quality reference genomes to deliver contiguous, structurally faithful assemblies; comprehensive pan-genomes to capture presence/absence variation and structural polymorphism across germplasm; and precise gene editing to target coding, regulatory, and structural features alike. Together, these tools chart a path toward mechanism-based breeding, enabling purposeful, design-driven trait improvement in peas and, by extension, other legumes.

Objective:To evaluate the diagnostic performance of the 0-2 h high-sensitivity cardiac troponin T (hs-cTnT) cutoff recommended by the guidelines for the rule-out and rule-in diagnosis of suspected non-ST-segment elevation myocardial infarction (NSTEMI) patients of different age groups.Methods:This is a retrospective cohort study. Clinical data of 4 050 suspected NSTEMI patients who visited the Chest Pain Center of Zhongshan Hospital affiliated with Fudan University from January 2020 to December 2021 were retrospectively analyzed. Patients who visited from January 2020 to April 2021 (2 650 patients) were included as derivation cohort, and those who visited from May to December 2021 (1 400 patients) were included as validation cohort. The diagnostic performance of the guideline-recommended hs-cTnT 0-2 h cutoff for the rule-out and rule-in of NSTEMI diagnosis was compared among subgroups of patients aged ≤60, >60-70, and >70 years in the derivation group. Rule-out sensitivity, negative predictive value, and rule-out proportion, rule-in specificity, positive predictive value, and rule-in proportion were assessed. Cutoffs were established for subgroups with relatively lower diagnostic performance and validated in the validation group. Major adverse cardiovascular events (MACE) within 30 days after patient visit were used as the outcome, and survival curves were plotted using Kaplan-Meier curves, log-rank tests were used to analyze the incidence of MACE.Results:The sensitivity for ruled-out NSTEMI using the guideline-recommended 0-2 h cutoff in the subgroups of patients aged ≤60, >60-70, and >70 years in the derivation group was 100%; the negative predictive value was 100%; the ruled-out rates were 47.6% (331/696), 45.9% (491/1 070), and 28.5% (252/884), respectively. The specificity for ruled-in NSTEMI was 88.3%, 90.9%, and 86.4%, respectively; the positive predictive values were 55.3%, 59.3%, and 58.2%, respectively; the ruled-in rates were 22.6% (157/696), 19.5% (209/1 070), and 27.0% (239/884), respectively. With a requirement of sensitivity and negative predictive value >99%, the ruled-out cutoff for the subgroup of patients aged >70 years in the derivation group was established as 0 h hs-cTnT <6 ng/L or 0 h hs-cTnT<22 ng/L and 0-2 h Δhs-cTnT <5 ng/L, which increased the ruled-out rate of the subgroup aged >70 years to 45.6% (403/884). In the validation group, 42.2% (196/465) patients could be ruled-out. The incidence of MACE within 30 days for ruled-out patients aged >70 years using the established cutoff was 0.Conclusion:The diagnostic performance for the ruled-out and ruled-in diagnosis using the guideline-recommended 0-2 h hs-cTnT cutoff are relatively consistent across different age groups, but the ruled-out rate for patients aged >70 years is lower than for those aged ≤60 and >60-70 years. The ruled-out cutoff established in this study can be used to improve diagnostic performance of thus indicator on suspected NSTEMI patients.

Objective:To investigate the feasibility and clinical efficacy of percutaneous vertebroplasty (PVP) with measured saturated bone cement injection in the treatment of elderly patients with stage Ⅱ Kümmell's disease.Methods:A retrospective analysis was conducted to analyze the clinical data of the 41 elderly patients with stage Ⅱ Kümmell's disease who had been treated at Department of Spinal Orthopedics, Zhengzhou Orthopedic Hospital from June 2017 to June 2023 by PVP with bone cement injection into the intravertebral vacuum cleft. According to the amount of bone cement injected, the patients were divided into a saturated volume group (bone cement injection metered ≥ 150% of the cleft volume preoperatively measured) in which there were 21 cases, 4 males and 17 females, aged (78.4±5.2) years and a conventional volume group (bone cement injection metered was 100% to 120% of the cleft volume preoperatively measured) in which there were 20 cases, 6 males and 14 females, aged (79.5±7.4) years. The operative time, vacuum cleft volume measured, actual volume of bone cement injected, and percentage of bone cement injected were compared between the 2 groups. Visual analogue scale (VAS) for pain and Oswestry disability index (ODI) were compared between preoperation, postoperative 3 days, and the final follow-up in the 2 groups, as well as between the 2 groups. Cement leakage and other complications were documented.Results:The differences in the preoperative general data were not statistically significant between the 2 groups, indicating comparability ( P>0.05). All the 41 elderly patients successfully completed their surgery. Follow-up time was (18.1±3.3) months. The operative time [(39.7±7.5) min], actual volume of bone cement injected [(5.6±0.9) mL], and percentage of bone cement injected (1.8%±0.3%) in the saturated volume group were all significantly greater than those in the conventional volume group [(35.5±4.9) min, (4.4±1.0) mL, and 1.2%±0.1%] ( P<0.05). Postoperatively, the incisions healed completely in all patients, with no such complications as cement-related adverse reactions. Cement leakage occurred in 2 patients in the conventional volume group, leading to lumbar pain or discomfort after activity, which was relieved by cement reinforcement and nail-rod internal fixation. VAS pain scores and ODIs at 3 d postoperatively and at the final follow-up were significantly improved in all patients compared with preoperation ( P<0.05). At the final follow-up, both VAS pain score and ODI in the saturated volume group improved significantly greater than those in the conventional volume group ( P<0.05). None of the patients had complications like cement displacement at the final follow-up. Conclusion:PVP with measured saturated bone cement injection into the intravertebral vacuum clefts is a safe and effective treatment for stage Ⅱ Kümmell's disease in elderly patients, offering a new minimally invasive option.

Objective To investigate the effect of microRNA(miR)-34a-5p on neurological function of rats with intracerebral hemorrhage(ICH)by adjusting PTEN-induced kinase 1(PINK1)/Parkin pathway.Methods SD rats were assigned into sham surgery group(Sham),ICH group,inhibitor NC group,miR-34a-5p inhibitor group,miR-34a-5p inhibitor+DMSO group,and miR-34a-5p inhibitor+Mdivi-1 group,with 8 rats in each group.Modified neurological severity score(mNSS)was used to assess changes in neurological function of rats;HE staining was used to observe the pathological changes in the brain tissue of rats;transmission electron microscopy was used to observe autophagy in brain tissue;TUNEL staining was used to observe cell apoptosis;qRT-PCR experiment was used to detect the mRNA levels of miR-34a-5p,PINK1 and Parkin in the brain tissues;Western blot experiments were used to measure PINK1,Parkin,Beclin1 and P62 proteins in the brain tissues of rats;dual luciferase reporter gene assay was used to determine the targeting relationship between miR-34a-5p and PINK1.Results Compared with the inhibitor NC group,the miR-34a-5p inhibitor group demonstrated lower levels of neuronal necrosis,red blood cell amount,inflammatory cell amount,autophagic vacuole amount,mNSS score,TUNEL positivity rate,miR-34a-5p expression and p62 protein,but higher levels of PINK1,Parkin mRNA and protein expression,and Beclin1 protein expression(P＜0.05).Compared with the miR-34a-5p inhibitor+DMSO group,the changes mentioned above in rat of the miR-34a-5p inhibitor+Mdivi-1 group are all reversed(P＜0.05).In the dual luciferase reporter gene experiment,the relative luciferase activity of cells in the miR-34a-5p mimic and PINK1-WT cotransfected group was greatly reduced(P＜0.05).Conclusion The downregulation of miR-34a-5p may alleviate neurological dysfunction in ICH rats by adjusting PINK1/Parkin pathway.