Soil cadmium (Cd) pollution is one of the major environmental problems globally. Ophiopogon japonicus, a multifunctional plant extensively used in traditional Chinese medicine, has demonstrated potential in environmental remediation. This study investigated the Cd accumulation pattern of O. japonicus under cadmium stress and identified the heavy metal ATPase (HMA) family members in this plant. Our results demonstrated that O. japonicus exhibited a Cd enrichment factor (EF) of 2.75, demonstrating strong potential for soil Cd pollution remediation. Nine heavy metal ATPase (HMA) members of P1B-ATPases were successfully identified from the transcriptome data of O. japonicus, with OjHMA1-OjHMA6 classified as the Zn/Co/Cd/Pb-ATPases and OjHMA7-OjHMA9 as the Cu/Ag-ATPases. The expression levels of OjHMA1, OjHMA2, OjHMA3, and OjHMA7 were significantly up-regulated under Cd stress, highlighting their crucial roles in cadmium ion absorption and transport. The topological analysis revealed that these proteins possessed characteristic transmembrane (TM) segments of the family, along with functional A, P, and N domains involved in regulating ion absorption and release. Metal ion-binding sites (M4, M5, and M6) existed on the TM segments. Based on the number of transmembrane domains and the residues at metal ion-binding sites, the plant HMA family members were categorized into three subgroups: P1B-1 ATPases, P1B-2 ATPases, and P1B-4 ATPases. Specifically, the P1B-1 ATPase subgroup included the motifs TM4(CPC), TM5(YN[X]₄P), and TM6(M[XX]SS); the P1B-2 ATPase subgroup featured the motifs TM4(CPC), TM5(K), and TM6(DKTGT); the P1B-4 ATPase subgroup contained the motifs TM4(SPC) and TM6(HE[X]GT), all of which were critical for protein functions. Molecular docking results revealed the importance of conserved sequences such as CPC/SPC, DKTGT, and HE[X]GT in metal ion coordination and stabilization. These findings provide potential molecular targets for enhancing Cd uptake and tolerance of O. japonicus by genetic engineering and lay a theoretical foundation for developing new cultivars with high Cd accumulation capacity.
Cadmium/metabolism* ; Adenosine Triphosphatases/metabolism* ; Ophiopogon/drug effects* ; Soil Pollutants/toxicity* ; Plant Proteins/metabolism* ; Stress, Physiological ; Multigene Family ; Gene Expression Regulation, Plant

Objective To explore correlations of expression levels of microRNA-147(miR-147),Ki-67 and carcinoembryonic antigen(CEA)with lymph node metastasis of invasive lung adenocarci-noma.Methods A total of 160 patients with invasive pulmonary adenocarcinoma were selected as study subjects.Based on presence of lymph node metastasis,patients were divided into lymph node metastasis group(n=74)and non-lymph node metastasis group(n=86).Immunohistochemistry was employed to detect the expression levels of miR-147 and Ki-67 in cancer tissues.The serum CEA level was measured using the chemiluminescence method.The correlations of the expression levels of miR-147,Ki-67 and serum CEA with the clinicopathological characteristics of patients were analyzed.The value of miR-147,Ki-67 and CEA in predicting lymph node metastasis was evaluated using the receiver operating characteristic(ROC)curve.Results The expression level of miR-147 in the lymph node metastasis group was significantly lower than that in the non-lymph node metastasis group,while the expression levels of Ki-67 and serum CEA were significantly higher in the lymph node me-tastasis group than in the non-lymph node metastasis group(P＜0.05).Patients with a tumor diameter≥3 cm or TNM stage Ⅲ to Ⅳ had significantly lower miR-147 expression levels in cancer tissues compared to those with a tumor diameter＜3 cm or TNM stage Ⅰ to Ⅱ(P＜0.05).The Ki-67 ex-pression level in cancer tissues was significantly higher in patients with a tumor diameter ≥3 cm than in those with a tumor diameter＜3 cm(P＜0.05).The serum CEA level was significantly higher in patients with TNM stage Ⅲ to Ⅳ than in those with TNM stage Ⅰ to Ⅱ(P＜0.05).The expres-sion level of miR-147 was negatively correlated with Ki-67,serum CEA and lymph node metastasis(P＜0.05);Ki-67 and serum CEA were positively correlated with lymph node metastasis(P＜0.05);Ki-67 was positively correlated with serum CEA(P＜0.05).The areas under the ROC curves for miR-147,Ki-67 and CEA in predicting lymph node metastasis were 0.785,0.835 and 0.798,respectively(P＜0.05).Conclusion The expression levels of miR-147 and Ki-67 in cancer tissues and the serum CEA level are correlated with lymph node metastasis in invasive pulmo-nary adenocarcinoma.

Objective:This study aimed to retrospectively analyze the incidence and influencing factors of tricuspid regurgitation (TR) in the short term after pacemaker lead implantation at the Second Affiliated Hospital of Zhejiang University School of Medicine, so as to provide evidence for understanding pacemaker lead-related TR.Methods:Consecutive patients who underwent single- or dual-chamber permanent pacemaker implantation between June 2019 and December 2023 in the Department of Cardiology were enrolled. General clinical data and relevant parameters were collected. Changes in TR severity before and shortly after the procedure were assessed using echocardiography. TR progression was defined as an increase by one grade or more, and TR improvement as a decrease by one grade or more. Logistic regression analysis was employed to identify factors associated with TR progression.Results:A total of 219 patients were included (128 males, 91 females), with a mean age of 69.7 ± 11.2 years. The median follow-up time was 99 (26, 199) days. TR remained unchanged in 114 patients (52.1%), improved in 46 (21.0%)—including 36 (16.4%) with one-grade reduction, 9 (4.1%) with two-grade reduction, and 1 (0.5%) with three-grade reduction—and progressed in 59 patients (26.9%). Among those with progression, 51 (23.3%) had mild-to-moderate TR worsening by one grade, and 8 (3.7%) had moderate or worse TR worsening by at least two grades. Notably, one case involved lead perforation of the leaflet and two cases had lead impingement. Compared with the non-progression group ( n = 114), pacemaker indication (AV block vs. sick sinus syndrome), baseline left atrial diameter, pulmonary artery systolic pressure (PASP), and the severity of mitral regurgitation (MR) and TR were significantly associated with TR progression or improvement (all P < 0.05). Ordinal logistic regression analysis identified preoperative TR severity [ OR=10.57 (3.77–29.68), P < 0.001] and pacemaker indication [ OR=0.452 (0.222–0.918), P = 0.028] as independent predictors of postoperative TR progression. Patients with AV block were more likely to receive left bundle branch pacing ( P < 0.001), which may contribute to their lower risk of TR. Conclusions:Short-term progression of TR after pacemaker implantation is relatively common, although severe TR remains rare. Preoperative TR severity and pacemaker indication are independent predictors of short-term TR progression. The use of physiological pacing modalities may help reduce the incidence of TR following pacemaker lead implantation.

Soybean meal (SBM) prepared by soybean crushing is the most popular protein source in the poultry and livestock industries (Cai et al., 2015) due to its economic manufacture, high protein content, and good nutritional value. Despite these benefits, SBM contains various antigen proteins such as glycinin and β-conglycinin, which account for approximately 70% of the total proteins of the SBM and reduce digestibility and damage intestinal function (Peng et al., 2018). Treating SBM with proteases (neutrase, alcalase, and trypsin) or fermentation can eliminate these antigen proteins (Contesini et al., 2018). Because of its safety and rapid growth cycle, Bacillus strains are considered ideal for the fermentation industry (Yao et al., 2021). SBM fermented by Bacillus yields products with high nutritional value and low levels of antinutritional factors (ANFs), stimulating research in this area (Yuan et al., 2017). Kumari et al. (2023) demonstrated that fermentation with Bacillus species effectively degrades antigen proteins and increases crude protein content. The degradation of antigen proteins relies on protease hydrolysis. Low protease production is the major obstacle hindering the widespread use of microbial fermentation techniques.
Bacillus amyloliquefaciens/metabolism* ; Fermentation ; Glycine max/metabolism* ; Soybean Proteins/metabolism* ; Peptide Hydrolases/metabolism* ; Ribosomes/metabolism* ; Globulins ; Antigens, Plant ; Seed Storage Proteins

Probiotics are natural systems bridging synthetic biology, physical biotechnology, and immunology, initiating innate and adaptive anti-tumor immune activity. We previously constructed an all-in-one engineered food-grade probiotic Lactococcus lactis (FOLactis) which could boost the crosstalk among different immune cells such as dendritic cells (DCs), natural killer cells, and T cells. Herein, considering the limited clinical efficacy of naked personalized neoantigen peptide vaccines, we decorate FOLactis with tumor antigens by employing a Plug-and-Display system comprising membrane-inserted peptides. Intranodal injection of FOLactis coated with neoantigen peptides (Ag-FOLactis) induces robust DCs presentation and neoantigen-specific cellular immunity. Notably, Ag-FOLactis not only triggers a 45-fold rise in the quantity of locally reactive neoantigen-specific T cells but also induces epitope spreading in both subcutaneous and metastatic tumor-bearing models, leading to potent inhibition of tumor growth. These findings imply that Ag-FOLactis represents a powerful platform to rapidly and easily display antigens, facilitating the development of a bio-activated platform for personalized therapy.

Objective:To evaluate the epidemiological characteristics and explore the associated factors of breakthrough cases (BC) from Public Health Emergency Events (PHEEs) of varicella in Zhejiang Province from 2019 to 2022.Methods:Data on cases were obtained from the China Information System for Disease Control and Prevention and the PHEEs Reporting Information Database of Varicella in Zhejiang Province. History records were matched through the Zhejiang Provincial Immunization Information System. Descriptive analysis and multiple logistic regression model with a bidirectional stepwise selection method were performed to explore associated factors for BC during 2019-2022.Results:A total of 144 276 varicella cases were reported from 2019 to 2022, with the annual reported incidence of 47.35-82.80 cases per 100 000 population. Among these cases, 109 172 were non-breakthrough cases (NBC, accounting for 75.67%), 34 517 were BC (23.92%), and the rest 587 cases had unclear vaccination history on varicella (0.41%). A total of 214 PHEEs of varicella were reported, of which 99.07% occurred in school settings. The proportion of PHEEs that occurred in high school increased significantly as time went on ( χ2trend=5.742, P=0.017). Multiple logistic regression model which focused on "BC vs. NBC (as the reference)" indicated that the year of onset ( OR=1.585, 95% CI:1.343-1.878), the month of onset (taking January as the reference, OR=2.311-15.652), city (taking Hangzhou as the reference, Jiaxing OR=2.370, Jinhua OR=2.197, Lishui OR=0.134), age ( OR=0.887, 95% CI: 0.826-0.944), PHEEs setting (taking "primary school and below" as the reference, "high school and above" OR=0.516, 95% CI: 0.305-0.897), and the number of rashes ( OR=0.569, 95% CI: 0.458-0.703) were associated factors. Multiple logistic regression model which focused on "two-dose BC vs. one-dose BC (as the reference)" showed that the age of initial vaccination ( OR=0.045, 95% CI: 0.014-0.107), the time interval from onset to the last dose ( OR=0.037, 95% CI: 0.011-0.087) and the age of onset ( OR=20.724, 95% CI: 8.383-72.485) were associated factors. Conclusion:During 2019-2022, the reported high-risk group of varicella in Zhejiang Province has shifted to adolescents and young adults. Although vaccination could not completely prevent the onset of VZV, it could relieve clinical symptoms and delay the age of onset.

To investigate the correlation of polymorphisms at the rs1837253 and rs3806933 loci of the thymic stromal lymphopoietin(TSLP)gene with asthma susceptibility and Eos,IgE,and FeNO levels in children.A total of 143 asthmatic children were selected as the study group,and 112 healthy children undergoing routine health examinations at the same hospital were chosen as the control group.The MassARRAY SNP genotyping technology was used to detect the genotypes at two loci,while serum IgE levels were determined by using the turbidimetric scattering method.The distribution differences in genotype and allele frequencies between the two groups were analyzed,along with the effects of different genotypes on Eos,IgE,and FeNO levels.There was no statistically significant difference in the distribution of rs1837253 allele and genotype frequencies as well as rs3806933 allele frequencies between the two groups(P＞0.05).However,asthma group rs3806933 CT genotype frequency was higher than the control group,and CC genotype frequency was lower than the control group(P＜0.05).Compared with the wild-type genotypes,children who carried rs1837253 CT+CC and rs3806933 CT,CT+TT genotypes had an increased risk of asthma(CT+CC vs TT:OR=2.737,95%CI:1.514-4.945;CT vs CC:OR=2.058,95%CI:1.194-3.543;CT+TT vs CC:OR=1.843,95%CI:1.109-3.062).There was an overall statistical difference in Eos counts among the three genotypes at the rs1837253 locus in the asthma group(P＜0.05,correction for multiple comparisons P＞0.05),but not in the control group(P＞0.05).There were no statistically significant differences in Eos%,IgE,and FeNO levels among the genotypes at the two loci and no significant difference in Eos counts among genotypes at the rs3806933 loci(P＞0.05).Taken together,polymorphisms at rs1837253 and rs3806933 loci in the promoter region of the TSLP gene are associated with asthma susceptibility in children.rs3806933 CT genotype may serve as a potential genetic marker for asthma,and rs1837253 CT+CC and rs3806933 CT+TT genotypes are risk factors for asthma in children;the rs1837253 locus polymorphism tended to affect blood Eos counts,while the two SNPs were not associated with Eos%,serum IgE,and FeNO levels.

Objective:To investigate the clinical characteristics and management status of children with Turner syndrome (TS) in China.Methods:As a cross-sectional study, 1 089 TS patients were included in the database of the National Collaborative Alliance for the Diagnosis and Treatment of Turner Syndrome from August 2019 to November 2023. Clinical characteristics (growth development, sexual development, organ anomalies, etc.), karyotypes, auxiliary examinations, and treatments were collected and analyzed.Results:Among the 1 089 TS cases, 809 were recorded karyotypes. The karyotype distribution was as follows: 45, X in 317 cases (39.2%), X chromosome structural variants (including partial deletions of p or q arm, ring chromosome, and marker chromosome) in 89 cases (11.0%), 45, X/46, XX mosaicism in 158 cases (19.5%), mosaicism with X chromosome structural variants in 209 cases (25.8%), and presence of Y chromosome material in 36 cases (4.4%). Among the 824 TS cases, the age of diagnosis was 9.7(6.4, 12.2) years, with a height standard deviation score (HtSDS) of -3.1±1.2. Five hundred and fifty three cases underwent growth hormone (GH) stimulation test, and 352 cases (63.7%) had GH peak values <10 μg/L and 75.9% (577/760) had low IGF1 levels, with IGF1 SDS ≤-2 accounting for 38.2% (290 cases). Among 471 cases aged ≥8 years, 132 cases (28.0%) showed spontaneous sexual development (mean bone age (11.0±1.7) years), 10 cases had spontaneous menarche (mean bone age (12.0±2.2) years), and 2 cases had regular menstrual cycles. Common physical features included cubitus valgus (311 cases (28.5%)), neck webbing (188 cases (17.2%)), low posterior hairline (185 cases (17.0%)), shield chest (153 cases (14.0%)), high arched palate (127 cases (11.6%)), short fourth metacarpal (43 cases (3.9%)), and spinal abnormalities (38 cases (3.5%)). Congenital cardiovascular and urogenital anomalies occurred in 91 cases (19.4%) and 66 cases (12.0%)respectively. Abdominal ultrasound in 33 cases (7.2%) indicated fatty liver, hepatomegaly, intrahepatic bile duct stones, and splenomegaly. Among 23 cases undergoing oral glucose tolerance test (OGTT) test, 2 were diagnosed with diabetes mellitus and 4 with impaired glucose tolerance. Following diagnosis, 669 cases (80.7%) received rhGH treatment at a chronological age of (9±4) years and bone age of (8.3±3.2) years. Additionally, 112 cases (19.4%) received sex hormone replacement therapy starting at the age of (14±4) years and bone age of (12.6±1.2) years.Conclusions:The karyotypes of 45, X and mosaicism were most common in Chinese children with TS. The clinical manifestations were mainly short stature and gonadal dysplasia. However, a few TS children could be in the normal range of height, and some cases among those aged of ≥8 years old had spontaneous sexual development. Some exhibited physical features, congenital cardiovascular and urogenital anomalies, and dysfunction of the hypothalamic-pituitary-IGF1 axis. Moreover, a few of them developed impaired glucose tolerance and diabetes mellitus. Following diagnosis, most of the patients received rhGH treatment, and a few of them received sex hormone replacement therapy.

Objective:To build a risk pre-control scheme for postoperative pulmonary infection in elderly patients with hip fracture based on the evidence-based evidence, so as to provide reference for clinical practice.Methods:From March 2021 to March 2022, a draft pre-control plan for postoperative pulmonary infection risk in elderly patients with hip fracture was developed based on previously included evidence and clinical conditions. Using the expert meeting method, the preliminary draft plan was revised and improved, and the practical plan for pre-controlling the risk of postoperative pulmonary infection in elderly patients with hip fractures was ultimately determined.Results:The 105 pieces of evidence summarized in the previous study formed 31 review indicators, and the risk pre-control plan of pulmonary infection after hip fracture in the elderly was constructed, which included 11 perioperative risk factor assessment items and 35 perioperative risk pre-control measures.Conclusions:The risk pre-control scheme of postoperative pulmonary infection in elderly patients with hip fracture is scientific and feasible, which can provide a certain basis for optimizing clinical practice, reducing the incidence of postoperative pulmonary infection and promoting patient recovery.

Objective:To explore the symptom management experience in young and middle-aged patients with home peritoneal dialysis.Methods:Using the descriptive phenomenological research method and purposive sampling method, 13 young and middle-aged peritoneal dialysis patients were selected for semi-structured interviews, and the interview data was analyzed and sorted out to extract themes.Results:A total of four themes were summarized, including difficulties in symptom management (lack of symptom management knowledge, insufficient symptom perception ability), effect of poor symptom management effectiveness (limited daily life behavior, weakened family roles, obstacles in returning to the workplace, withdrawal of social activities and increased economic burden), polarized symptom management coping strategies (positive and negative responses) and multifaceted symptom management needs (longing for new treatment methods, hoping for disease knowledge popularization and craving for social support in various aspects) .Conclusions:There are many obstacles and needs in the process of symptom self-management of young and middle-aged home peritoneal dialysis patients. It is suggested that medical staff should combine the characteristics and psychology of middle-aged and young peritoneal dialysis patients, implement targeted intervention measures, and improve their symptom management ability.