Objective To investigate the effects of Echinococcus multilocularis infection on levels of memory T (Tm) cells and their subsets in lymph nodes of mice at different stages of infection, so as to provide new insights into immunotherapy for alveolarechinococcosis. MethodsTwenty-four C57BL/6J mice aged 6 to 9 weeks were randomly divided into the infection group and the control group, of 12 mice in each group. Mice in the infection group were administered with 3 000 E. multilocularis protoscoleces via portal venous injection, while animals in the control group were administered with an equal volume of physiological saline. Three mice from each group were sacrificed 4, 12 weeks and 24 weeks post-infection, and lymph nodes were sampled and stained with hematoxylin and eosin (HE) to investigate the histopathological changes of mouse lymph nodes in the infection group. The expression and localization of T lymphocyte surface markers CD3, CD4, and CD8 were observed in mouse lymph nodes using immunohistochemical staining. In addition, lymphocyte suspensions were prepared from mouse lymph nodes in both groups at different time points post-infection, and the levels of Tm cell subsets and their secreted cytokines were detected using flow cytometry. Results HE staining showed diffuse structural alterations in the subcapsular cortical and paracortical regions of mouse lymph nodes in the infection group 4 weeks post-infection with E. multilocularis. Immunohistochemical staining detected CD3, CD4 and CD8 expression in mouse lymph nodes in both groups. Flow cytometry revealed higher proportions of CD4⁺ Tm cells [(55.3 ± 4.8)% vs. (38.8 ± 6.1)%; t = -4.259, P < 0.05] and CD4⁺ tissue-resident Tm (Trm) cells [(57.7 ± 3.7)% vs. (34.1 ± 11.2)%; t = -3.990, P < 0.05] in mouse lymph nodes in the infection group than in the control group 4 weeks post-infection, and higher proportions of CD4⁺ Tm cells [(34.6 ± 3.2)% vs. (23.3 ± 7.5)%; t = -2.764, P < 0.05] and CD4⁺ Trm cells [(44.0 ± 1.9)% vs. (31.2 ± 1.5)%; t = -4.039, P < 0.05] in mouse lymph nodes in the infection group than in the control group 24 weeks post-infection. The proportions of CD8⁺ Tm cells were higher in the infection group than in the control group 4 weeks [(56.8 ± 2.7)% vs. (43.9 ± 5.2)%; t = -4.416, P < 0.01] and 12 weeks post-infection [(25.4 ± 2.7)% vs. (12.0 ± 2.6)%; t = -2.552, P < 0.05], while the proportions of tumor necrosis factor (TNF)-α⁺ CD4⁺ T cells [(15.7 ± 5.0)% vs. (49.4 ± 6.4)%; t = 7.150, P < 0.01], TNF-α⁺CD8⁺ T cells [(20.7 ± 5.5)% vs. (57.5 ± 8.4)%; t = -6.694, P < 0.01], and TNF-α⁺ CD8⁺ Tm cells [7.0% (1.0%) vs. 31.0% (11.0%); Z = -2.236, P < 0.05] were lower in the infection group than in the control group 24 weeks post-infection. Conclusions Tm cells levels are consistently increased in lymph nodes of mice at different stages of E. multilocularis infection, with Trm cells as the predominantly elevated subset. The impaired capacity of CD8⁺ Tm cells to secrete the effector molecule TNF-α in mouse lymph nodes at the late-stage infection may facilitate chronic parasitism of E. multilocularis.

ObjectiveTo investigate the effects of rhizosphere organic acids secreted by the roots of Salvia miltiorrhiza on continuous cropping obstacles. MethodsThe mixed solution of organic acids in the rhizosphere of S. miltiorrhiza in continuous cropping and rotation cropping was added to the hairy roots subcultured for 21 days， and samples were collected on days 0， 2， 4， 6， 8， and 10. The changes of biomass， effective components， primary metabolites， secondary metabolites， antioxidant enzymes， and hormones in hairy roots of S. miltiorrhiza were observed and determined. ResultsCompared with the rotation cropping group and the blank control group， the simulation of organic acid secretion from the roots of S. miltiorrhiza had a significant inhibitory effect on the growth of hairy roots and decreased the content of effective components as well as total sugar and total protein in primary metabolites. Compared with the blank control group， the rotation cropping group and the continuous cropping group showed total sugar and total protein content decreases of 33.9% and 5.1%， respectively. On the other hand， the secretion of organic acids from S. miltiorrhiza roots significantly promoted the accumulation of total phenolic acids and total tanshinone， which showed increases of 14.6% and 1.6%， respectively， in continuous cropping group and rotation cropping group compared with the blank control group. ConclusionThe organic acid environment under continuous cropping significantly inhibited the growth of hairy roots and the accumulation of primary metabolites， while promoting the synthesis and accumulation of secondary metabolites of S. miltiorrhiza.

[摘 要] 目的：探究肺癌磷酸甘油酸变位酶1（PGAM1）对肺癌LLC细胞增殖和迁移的调控作用，以及PGAM1对肿瘤微环境中CD8+ T细胞功能和浸润的影响。方法：将shPGAM1及shNC慢病毒感染LLC细胞，筛选稳定细胞，分别命名为shPGAM1组和NC组，WB和qPCR法检测两组细胞中PGAM1蛋白和mRNA的表达水平。CCK-8法和实时细胞分析仪检测敲低PGAM1对LLC细胞增殖和迁移的影响；流式细胞术检测与两组细胞分别体外共培养后CD8+ T细胞功能性受体（TIM-3、PD-1、GrzmB、Ki67）表达的变化。构建小鼠肺癌LLC细胞皮下移植瘤模型，监测PGAM1表达对肿瘤生长的影响，通过流式细胞术检测敲低PGAM1对肿瘤微环境中CD8+ T细胞浸润的影响。结果：shPGAM1组细胞中PGAM1蛋白和mRNA表达水平较NC组均显著降低。敲低PGAM1可降低LLC细胞的增殖和迁移能力（Ρ < 0.000 1或Ρ < 0.05）。与shPGAM1组细胞共培养后，CD8+ T细胞的耗竭标志物（TIM-3、PD-1）表达均降低（Ρ < 0.000 1或Ρ < 0.01）。敲低PGAM1后肿瘤生长受到显著抑制，且肿瘤组织中CD8+ T细胞浸润增加（Ρ <0.000 1）。结论：靶向敲低PGAM1可抑制肿瘤细胞增殖、迁移，降低CD8⁺ T细胞耗竭标志物的表达及促进肿瘤内T细胞浸润，双重调控肿瘤生长与抗肿瘤免疫。

Edentulous patients often present with severe alveolar bone resorption, restructured maxillofacial anatomy, and loss of occlusal relationships, making implant-supported rehabilitation technically more challenging—particularly in terms of guide stability, implant positioning accuracy, and prosthesis design. Traditional treatment workflows largely rely on clinician experience, which is inherently subjective and limits the ability to achieve precise, controlled implant placement and predictable restorative outcomes. In recent years, the widespread adoption of digital technologies has brought transformative progress to implantology for edentulous jaws. Innovations span from preoperative imaging and 3D reconstruction, intelligent surgical planning, personalized guide design, dynamic navigation, and robotic-assisted implant placement, to digital prosthesis design and immediate loading protocols. These advancements have markedly improved surgical precision, procedural efficiency, and patient satisfaction. This article systematically reviews the key applications and clinical value of digital technologies across the various stages of implant rehabilitation in edentulous cases. We also highlight current challenges, such as high costs and dependence on specialized equipment. Finally, we explore future directions toward more intelligent and integrated solutions that are driven by advances in artificial intelligence, multimodal image fusion, and robotics.

OBJECTIVE: To study incident and clinical characteristics of the coronary microcirculation dysfunction (CMD) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) by myocardial contrast echocardiography (MCE) and to explore the predictive value of CMD for in-hospital acute heart failure event. METHODS: One hundred and forty five patients with AMI who had received PCI and completed MCE during hospitalization in Peking University People' s Hospital from November 2015 to July 2021 were enrolled in our study. The patients were divided into CMD group and normal group according to the coronary microcirculation status detected by MCE. Clinical data and MCE data of the two groups were collected and analyzed. The acute heart failure event during hospitalization was described. A multivariate Logistic regression model was built to analyze the risk of acute heart failure in patients with CMD. A receiver operating characteristic (ROC) curve was drawn to evaluate the value of CMD in predicting acute heart failure event. RESULTS: CMD detected by MCE occurred in 87 patients (60%). Compared with normal group, patients with CMD had higher troponin I (TnI) peak level [52.8 (8.1, 84.0) μg/L vs. 18.9 (5.7, 56.1) μg/L, P=0.005], poorer Killip grade on admission (P=0.030), different culprit vessel (P < 0.001) and more patients had thrombolysis in myocardial infarction (TIMI) flow pre-PCI less than grade 3 in culprit vessel (65.1% vs. 43.1%, P=0.025). Meanwhile, patients with CMD had poorer left ventricular ejection fraction (LVEF) [52% (43%, 58%) vs. 61% (54%, 66%)], poorer global longitudinal strain (GLS) [-11.2% (-8.7%, -14.0%) vs.-13.9% (-10.8%, -17.0%)] and worse wall motion score index (WMSI) (1.58±0.36 vs. 1.25± 0.24) (P all < 0.001). Acute left heart failure happened in 13.8% of the CMD patients, which were significant higher than that in the patients with normal coronary microcirculation perfusion (1.7%, P=0.013). After correcting for the culprit vessel, the TIMI flow pre-PCI in the culprit vessel and the peak TnI value, the risk of acute left heart failure in the patients with CMD was still high (OR=9.120, 95%CI: 1.152-72.192, P=0.036). The area under ROC curve (AUC) was 0.677 (95%CI: 0.551-0.804, P=0.035). CONCLUSION The incidence of CMD detected by MCE in patients with AMI post-PCI was 60%. Patients with CMD have a higher risk of acute left heart failure during hospitalization.
Humans ; Heart Failure/physiopathology* ; Microcirculation ; Percutaneous Coronary Intervention/adverse effects* ; Myocardial Infarction/complications* ; Male ; Female ; Hospitalization ; Middle Aged ; Aged ; Echocardiography ; Coronary Circulation ; Predictive Value of Tests ; Troponin I/blood*

The focus of green analytical chemistry (GAC) is to minimize the negative impacts of analytical procedures on human safety, human health, and the environment. Several factors, such as the reagents used, sample collection, sample processing, instruments, energy consumed, and the quantities of hazardous materials and waste generated during analytical procedures, need to be considered in the evaluation of the greenness of analytical assays. In this study, we propose a greenness evaluation metric for analytical methods (GEMAM). The new greenness metric is simple, flexible, and comprehensive. The evaluation criteria are based on both the 12 principles of GAC (SIGNIFICANCE) and the 10 factors of sample preparation, and the results are presented on a 0-10 scale. The GEMAM calculation process is easy to perform, and its results are easy to interpret. The output of GEMAM is a pictogram that can provide both qualitative and quantitative information based on color and number.

Peptides are a particular molecule class with inherent attributes of some small-molecule drugs and macromolecular biologics, thereby inspiring continuous searches for peptides with therapeutic and/or agrochemical potentials. However, the success rate is decreasing, presumably because many interesting but less-abundant peptides are so scarce or labile that they are likely 'overlooked' during the characterization effort. Here, we present the biochemical characterization and druggability improvement of an unprecedented minor fungal RiPP (ribosomally synthesized and post-translationally modified peptide), named acalitide, by taking the relevant advantages of metabolomics approach and disulfide-bridged substructure which is more frequently imprinted in the marketed peptide drug molecules. Acalitide is biosynthetically unique in the macrotricyclization via two disulfide bridges and a protease (AcaB)-catalyzed lactamization of AcaA, an unprecedented precursor peptide. Such a biosynthetic logic was successfully re-edited for its sample supply renewal to facilitate the identification of the in vitro and in vivo antiparkinsonian efficacy of acalitide which was further confirmed safe and rendered brain-targetable by the liposome encapsulation strategy. Taken together, the work updates the mining strategy and biosynthetic complexity of RiPPs to unravel an antiparkinsonian drug candidate valuable for combating Parkinson's disease that is globally prevailing in an alarming manner.

Objective:To investigate the pollution levels and influencing factors of polybrominated diphenyl ethers (PBDEs) in household dust in five cities in northern China.Methods:Based on the "Chinese Indoor Environment and Health Surveillance" project carried out by the National Institute of Environmental Health, Chinese Center for Disease Control and Prevention in 2018-2019, during the warm season (April 2018 to September 2018) and the cold season (November 2018 to March 2019), Lanzhou in Northwest China, Shijiazhuang in North China, Panjin in Northeast China, Luoyang in Central China, and Qingdao in East China were selected as the research sites. A total of 87 families were recruited to study residences in real-life scenarios. At the same time, dust samples were collected to detect the concentration of PBDEs. The level of household environmental indicators was measured, and the residential building characteristics and family behavior habits were collected through questionnaires. A total of 142 valid dust samples and 140 valid questionnaires were obtained. The differences in PBDE concentrations across seasons, wind zones, residential building characteristics, and family habits were analyzed. The exploratory factor analysis was performed to investigate the possible sources of PBDEs, and multivariate linear regression was used to explore the factors influencing PBDEs in household dust.Results:The M ( Q1,Q3) of total PBDE concentrations in 142 household dust samples in five cities was 144.51 (106.61, 222.65) ng/g in the warm season and 145.10 (98.57, 180.65) ng/g in the cold season, respectively. There were seasonal differences in the concentration of ∑ 12PBDEs in Luoyang and Shijiazhuang ( P<0.01). The concentration of BDE-71 was highest among PBDE homologues, followed by BDE-66 and BDE-47. Three factors were extracted by exploratory factor analysis in the warm season, and the cumulative variance contribution rate was 67.90%. The multivariate linear regression showed that the house completion less than ten years [ β (95% CI): 0.186 (0.013, 0.359)], infrequent home cooking [ β (95% CI):-0.342 (-0.570, -0.114)], and increased residential PM 10 concentration [ β (95% CI): 0.001 (0.000, 0.002)] during the warm season, as well as the house far from driveway [ β (95% CI): 0.093 (0.013, 0.172)], house area less than 90 m 2 [ β (95% CI):-0.138 (-0.264, -0.013)], and lower residential xylene concentration [ β (95% CI):-0.006 (-0.011, -0.001)] during the cold season might be related to the elevated concentrations of ∑ 12PBDEs in household dust. Conclusion:The pollution of PBDEs in household dust in five northern cities is at a medium to high level. Years of house completion, frequency of cooking at home, residential PM 10 concentration, distance from house to driveway, house area, and residential xylene concentration may influence household PBDE concentrations.

Objective:To explore the characteristics, prevention and treatment strategies of lower urinary tract injury in transvaginal reconstructive pelvic surgery (vRPS).Methods:A retrospective analysis was conducted on 24 patients who suffered lower urinary tract injuries occuring in vRPS from January 2005 to June 2021, among which 4 cases were referred to our hospital from other hospitals.Results:(1) In our hospital, 1 952 patients underwent vRPS for anterior and (or) middle pelvic organ prolapse during that study period, with a 1.0% (20/1 952) incidence of lower urinary tract injuries occurring in 20 cases. (2) Ureteral injuries were observed in 14 cases who underwent transvaginal high uterosacral ligament suspension (1.4%, 14/966). The symptoms were relieved after the removal of sutures. (3) Bladder injuries occurred in 6 cases in our hospital, with 4 cases (0.7%, 4/576) in anterior transvaginal mesh surgery (aTVM), one (0.4%, 1/260) in colpocleisis, and one (0.7%, 1/150) in apical suspension for fornix prolapse. An additional 4 cases of bladder injury were referred to our hospital after aTVM. Among the 8 cases of bladder injury during aTVM, 2 cases were intraoperative incidents. Cystoscopy confirmed that the superficial branch or puncture rod of anterior vaginal mesh had penetrated into the bladder. Re-puncturing and placement of the mesh were successfully performed. No abnormalities were observed during a follow-up period of 4-5 years. Postoperative bladder injuries were identified in 6 cases, characterized by mesh erosion into the bladder and formation of calculi. These injuries were confirmed between 6 months to 2 years after vRPS. The exposed mesh and calculi in the bladder were removed through laparotomy or cystoscopy, followed up for 2-12 years. One case experienced slight re-erosion of mesh to the bladder.Conclusions:Lower urinary tract injuries are difficult to avoid in vRPS, particularly in transvaginal high uterosacral ligament suspension and aTVM. However, the incidence is low. Lower urinary tract injuries during vRPS could be easily detected and managed intraoperatively because of the use of cystoscopy. As long-term postoperative complications, erosion of transvaginal mesh to lower urinary tract postoperatively could be treated correctly, seldom with severe sequelae.

Objective:To evaluate the effect of esketamine on cerebral ischemia-reperfusion (I/R) injury and the association with mitochondrial stress in mice.Methods:The experiment was performed in two parts. Part Ⅰ Eighteen SPF male C57BL/6 mice, aged 8-12 weeks, with body mass index of 28-30 g, were divided into 3 groups ( n=6 each) by a random number table method: sham operation group (S group), cerebral I/R group (IR group), and esketamine plus cerebral I/R group (E+ IR group). Cerebral I/R was produced by occlusion of middle cerebral artery for 1 h followed by 24-h reperfusion in anesthetized mice.Esketamine 10 mg/kg was intraperitoneally injected at 20 min before developing the model in E group. Neurological function was evaluated using the Zea Longa score and balance beam test (Feeney score). The cerebral infarct size was determined by TTC staining. Part Ⅱ Primary cortical neurons were isolated and cultured and then divided into 3 groups ( n=42 each) using a random number table method: control group (group C), oxygen-glucose deprivation-reoxygenation (OGD/R) group, and esketamine plus OGD/R group (group E+ OGD/R). Cells were subjected to O 2-glucose deprivation for 1 h followed by restoration of O 2-glucose supply for 24 h. The cells were treated with 25 μmol/L esketamine for 40 min before preparing the model in E+ OGD/R group. The neuronal viability was measured by the CCK-8 assay. The ultrastructure of neurons was observed with a transmission electron microscope. The levels of reactive oxygen species (ROS), glutathione peroxidase (GSH-px) and malondialdehyde (MDA) were determined, and the mitochondrial membrane potential was determined by JC-1 kit. The neuronal apoptosis was detected by TUNEL staining, and the apoptosis rate of neurons was calculated. The expression of Bax, cytochrome C (CytC), cleaved-caspase-9, caspase-3 and cleaved-caspase-3 was detected by Western blot. Results:Part Ⅰ Compared with S group, the Zea Longa score, Feeney score and cerebral infarct size were significantly increased in IR group ( P<0.01). Compared with IR group, the Zea Longa score, Feeney score and cerebral infarct size were significantly decreased in E+ IR group ( P<0.01). Part Ⅱ Compared with C group, the cell viability and activity of GSH-px were significantly decreased, the apoptosis rate of neurons, levels of ROS and MDA, mitochondrial membrane potential, and cleaved-caspase-3/caspase-3 ratio were increased, and the expression of Bax, Cyt C and cleaved-caspase-9 was up-regulated in OGD/R group ( P<0.01). Compared with OGD/R group, the cell viability and activity of GSH-px were significantly increased, the apoptosis rate of neurons, levels of ROS and MDA, mitochondrial membrane potential, and cleaved-caspase-3/caspase-3 ratio were decreased, and the expression of Bax, Cyt C and cleaved-caspase-9 was down-regulated in E+ OGD/R group ( P<0.01). Conclusions:Esketamine can alleviate cerebral I/R injury in mice, and the mechanism may be related to inhibition of mitochondrial stress in neurons, improvement in mitochondrial function, and inhibition of mitochondria-dependent apoptosis in neurons.