Objective To investigate the nutritional quality characteristics of vitamin D3-fortified yogurt and explore its improving effect on vitamin D metabolism in the body under simulated weightlessness,thereby providing a theoretical basis for the development of functional foods.Methods Using reconstituted milk as the matrix and Vitamin D3(VD3)microcapsule powder as the fortifier,VD3-fortified yogurt was prepared.A systematic study was conducted to investigate the effects of different gradients(1.25 μg/100 mL,2.50 μg/100 mL,3.75 μg/100 mL,5.00 μg/100 mL,6.25 μg/100 mL)of VD3 microcapsule addition on its quality characteristics(titratable acidity,solid content,water-holding capacity,syneresis).In vivo assessments were conducted using a Sprague-Dawley(SD)rat tail-suspension model to simulate weightlessness.Levels in serum 25(OH)D3,1,25-(OH)2D3,calcium(Ca),and phosphorus(P)were detected using the enzyme-linked immunosorbent assay(ELISA)to evaluate its metabolic capacity.Results During fermentation(3 h),titratable acidity of VD?-fortified yogurt initially increased,then decreased,and eventually stabilized with rising microcapsule dosage,while total solid content remained consistent.WHC exhibited an initial increase followed by a decline,whereas syneresis showed an inverse trend.At an optimal dosage of 3.75 μg/100 mL,the yogurt displayed a dense and uniform network structure,characterized by non-Newtonian fluid behavior with shear-thinning properties.This formulation demonstrated robust structural stability under high-frequency mechanical stress,alongside desirable textural,flavor,and sensory attributes.Animal experiments revealed that the serum concentrations of 25(OH)D3,1,25-(OH)2D3,calcium,and phosphorus in the vitamin D?-fortified yogurt intervention group were significantly higher than those in the tail-suspended control group(P<0.05).Conclusion VD? microencapsulation technology effectively preserves and enhances the nutritional quality characteristics of yogurt and mitigates vitamin D metabolic dysregulation under simulated weightlessness.

Pyruvate kinase M2(PKM2)is closely linked to a variety of neurological disorders,involved in the onset and progression of a wide range of diseases,including Alzheimer's disease,Parkinson's disease,multiple sclerosis and traumatic brain injury through such mechanisms as aerobic glycolysis,oxidative stress,inflammation and apoptosis.This review is intended to provide an overview of the biological characteristics of PKM2 and its role in the pathophysiological mechanisms of neurological disorders.A better understanding of the correlations between PKM2 and the development of neurological diseases can offer new insights into and references for the clinical diagnosis and treatment of these conditions.

Objective:To investigate the effect of different timing of arterial -venous extracorporeal membrane oxygenation (VA-ECMO) on the prognosis of patients with acute myocardial infarction complicated with cardiogenic shock (AMICS).Methods:This study was a prospective cohort study. AMICS patients received VA-ECMO support primary percutaneous coronary intervention in Henan Provincial People's Hospital from May 2017 to July 2023 were divided into early VA-ECMO group and late VA-ECMO group. 64 AMICS patients who met the indications for VA-ECMO implantation, but did not revive VA-ECMO were included as control group. Demographic characteristics, coronary interventional (PCI) information and complications after VA-ECMO implantation were collected. The primary end points was 1-year survival, minor end point were in-hospital and perioperative death. Multivariate Logistic and Cox regression models were used to evaluate the effect of timing of VA-ECMO on prognosis of AMICS patients. Kaplan-Meier survival curve was used to analyze the 1-year survival outcome of the 3 groups.Results:A total of 143 AMICS patients were included, and materials of 136 patients entered in the final analysis, including 42 in the early VA-ECMO group, 34 in the late VA-ECMO group, and 60 in the non-VA-ECMO group. Compared with the late VA-ECMO group, the early VA-ECMO group had a higher ratio of PPCI after VA-ECMO, a longer D-to-B time, a shorter VA-ECMO support time, a higher success rate of VA-ECMO withdrawal, and a lower complication rate (all P<0.05). Compared with the early VA-ECMO group, the perioperative, in-hospital and 1-year mortality were significantly higher in Non-ECMO support (all P<0.05). There was no difference in perioperative and in-hospital mortality between the early VA-ECMO group and the late VA-ECMO group, but the 1-year mortality in the late VA-ECMO group was significantly higher ( P<0.05). Perioperative, in-hospital and 1-year mortality rates were lower in the late VA-ECMO group than in the no-VA-ECMO group, but the differences were not statistically significant. Multivariate Logistic and Cox regression analysis showed that after adjusting interference factors, early VA-ECMO was still a protective factor for in-hospital ( OR=0.244, P=0.015) and one year ( HR=0.308, P=0.001)mortality. Kaplan-Merier survival curve showed that compared with the late VA-ECMO group and the group without VA-ECMO, the early VA-ECMO group had the highest 1-year survival rate. Conclusion:Patients with AMICS may benefit more from early VA-ECMO than from late VA-ECMO support for PPCI.

Objective:To explore the feasibility of circulating tumor cell (CTC) dual-antibody enrichment and dual-antibody detection for epithelial-mesenchymal phenotypes in patients with hepatocellular carcinoma (HCC), and investigate the clinical diagnostic value of CTC typing in evaluating postoperative recurrence and prognosis of HCC.Methods:Of 89 HCC patients who underwent surgical treatment in Zhejiang Jinhua Guangfu Tumor Hospital from March 2020 to January 2024 were enrolled into this study, including 73 males and 16 females, aged (64.4±9.5) years old. The peripheral blood samples of patients were collected before operation. Epithelial CTC, mesenchymal CTC and hybrid epithelial-mesenchymal CTC in blood samples of patients with HCC were enriched and detected by EpCAM/CSV double capture antibodies and PanCK/CSV double detection antibodies. Kaplan-Meier analysis was employed to assess recurrence-free survival (RFS) and overall survival (OS) rates. Univariate and multivariate Cox regression were used to analyze the effects of different types of CTC on postoperative RFS and OS.Results:The detection rates of total CTC, epithelial CTC, mesenchymal CTC and hybrid epithelial-mesenchymal CTC were 92.1% (82/89), 64.0% (57/89), 62.9% (56/89) and 55.1% (49/89), respectively. Multivariate Cox regression analysis showed that HCC patients with more mesenchymal CTC ( HR=2.408, 95% CI: 1.580-3.668) and hybrid epithelial-mesenchymal CTC ( HR=1.840, 95% CI: 1.004-3.371) in peripheral blood had higher postoperative recurrence risk (both P<0.05). Univariate Cox regression showed patients with more total CTC ( HR=1.426, 95% CI: 1.040-1.954, P=0.028) was associated with survival. Conclusion:The technique of epithelial-mesenchymal phenotypes analysis of circulating tumor cells based on dual-antibody capture and dual-antibody detection is feasible. The number of mesenchymal CTC and hybrid epithelial-mesenchymal CTC before operation is the influencing factor of postoperative recurrence in patients with hepatocellular carcinoma.

Objective:To explore the changes of gait flexibility and stability in patients with Parkinson's disease (PD) 2 years after deep brain stimulation (DBS).Methods:Twenty PD patients accepted DBS in Department of Neurosurgery, Tianjin Huanhu Hospital from October 2019 to November 2021 were enrolled. Motor symptoms were evaluated by Movement Disorder Society-unified Parkinson's disease rating scale III (MDS-UPDRS-III) at preoperative medication-off state, postoperative medication-off state, and postoperative medication-on state. Mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) were used to assess the cognition and 39-item Parkinson's disease questionnaire (PDQ-39) was used to evaluate the quality of life at preoperative medication-on state and postoperative medication-on state. A three-dimensional gait analyzer was used to record the gait parameters during Instrumented Stand and Walk test (ISAW) at preoperative medication-off state, postoperative medication-off state, and postoperative medication-on state. Differences in motor symptom scores, cognitive scores, quality of life scores, as well as changes in gait flexibility and stability were compared before and after DBS.Results:(1) The MDS-UPDRS-Ⅲ scores at preoperative medication-off state, postoperative medication-off state, and postoperative medication-on state ([45.30±12.57], [24.95±10.74], [15.80±7.19]) were decreased successively, with significant differences ( P<0.05).(2) Compared with those before surgery, PD patients had significantly lower levodopa equivalent daily dose (LEDD), total scores of PDQ-39, and scores of question 9 "degree of concern about falling" in PDQ-39 at 2 years after DBS ([711.84±343.99] mg/d vs. [549.30±301.08] mg/d, 47.00[30.00, 64.00] vs. 13.50[7.75, 27.00], 2.00[0.00, 3.00] vs. 0.00[0.00, 1.75], P<0.05). (3) Compared with that at preoperative medication-off state, the arm swing velocity at postoperative medication-on state statistically increased in PD patients ( P<0.05); compared with those at preoperative medication-off state, the arm swing range and turning speed at postoperative medication-off and medication-on states significantly increased in PD patients ( P<0.05); compared with that at preoperative medication-off state, the turning duration at postoperative medication-off state statistically decreased in PD patients ( P<0.05). Compared with that at preoperative medication-off state, the range of motion of the trunk in the horizontal plane at postoperative medication-off and medication-on states increased significantly in PD patients ( P<0.05); compared with that at preoperative medication-off state, the range of motion in the sagittal plane of the lumbar, coronal plane of the trunk, and sagittal plane of the trunk all increased significantly in PD patients at postoperative medication-on state ( P<0.05); the mean velocity and root mean square acceleration at postoperative medication-on state increased significantly in PD patients compared with that at preoperative medication-off state ( P<0.05); conversely, the swing frequency at postoperative medication-off state decreased significantly in PD patients compared with that at preoperative medication-off state ( P<0.05). Conclusion:Two years after DBS, PD patients exhibit obviously improved gait, with enhanced flexibility, and dynamic and static stability.

OBJECTIVE: To investigate the incidence and potential risk factors associated with postoperative spinal epidural hematoma (SEH) following anterior cervical spine surgery (ACSS). METHODS: A retrospective analysis was conducted on the clinical data of patients who underwent ACSS for cervical spondylosis at Peking University Third Hospital between March 2013 and February 2022. Patients who developed postoperative SEH were categorized as the SEH group, while those in the cohort without SEH were randomly selected as the non-SEH group by individually matching with the same operator, same gender, same surgery year, and similar age (±5 years) at a ratio of 4 ∶ 1. The general condition, preoperative comorbidities, anticoagulant or antiplatelet therapy, preoperative coagulation and platelet counts, American society of Anesthesiologists physical status classification, cervical spondylosis classification, preoperative modified Japanese Orthopaedic Society score and cervical disability index score, surgical modality, surgical segment levels, ossification of the posterior longitudinal ligament among the surgical level, surgery duration, estimated blood loss, postoperative drainage volume, preoperative mean arterial pressure, mean arterial pressure during postoperative awakening periods, hospital stay and hospitalization cost were compared between the two groups. A bivariate Logistic regression model was applied to screen out the independent risk factors and calculate the odds ratios of indicators associated with SEH. Receiver operating characteristic curve and area under the curve (AUC) were used to describe the discrimination ability of the indicators. RESULTS: A total of 85 patients were enrolled in the study, including 17 patients in the SEH group and 68 patients in the non-SEH group. Seventeen patients with SEH underwent hematoma evacuation, and all of them were successfully treated and discharged from the hospital. Corpectomy (OR=7.247; 95%CI: 1.962-26.766; P=0.003) and the highest mean arterial pressure during awakening (OR=1.056; 95%CI: 1.002-1.113; P=0.043) were independent risk factors for SEH. The AUC values were 0.713 (95%CI: 0.578-0.848) and 0.665 (95%CI: 0.51-0.82) respectively. The patients with SEH had longer hospital stays (P < 0.001) and greater hospitalization costs (P=0.035). CONCLUSION Corpectomy and elevated maximum mean arterial pressure during awakening are independent risk factors for the development of postoperative SEH following ACSS. High-risk patients should be closely monitored during the perioperative period.
Humans ; Risk Factors ; Cervical Vertebrae/surgery* ; Retrospective Studies ; Hematoma, Epidural, Spinal/epidemiology* ; Incidence ; Male ; Female ; Postoperative Complications/etiology* ; Spondylosis/surgery* ; Logistic Models ; Length of Stay ; Middle Aged

Baylisascaris schroederi,a roundworm(ascaridoid)parasite specific to the bamboo-feeding giant panda(Ailuropoda melanoleuca),represents a leading cause of mortality in wild giant panda populations.Here,we present a 293-megabase chromosome-level genome assembly of B.schroederi to infer its biology,including host adaptations.Comparative genomics revealed an evolutionary trajectory accompanied by host-shift events in ascaridoid parasite lineages after host separations,suggesting their potential for transmission and rapid adaptation to new hosts.Genomic and anatomical lines of evidence,including expansion and positive selection of genes related to the cuticle and basal metabolisms,indicate that B.schroederi undergoes specific adaptations to survive in the sharp-edged bamboo-enriched gut of giant pandas by structurally increasing its cuticle thickness and efficiently utilizing host nutrients through gut parasitism.Additionally,we characterized the secretome of B.schroederi and predicted potential drug and vaccine targets for new control strategies.Overall,this genome resource provides new insights into the host adaptation of B.schroederi to the giant panda as well as the host-shift events in ascaridoid parasite lineages.Our findings on the unique biology of B.schroederi will also aid in the development of prevention and treatment measures to protect giant panda populations from roundworm parasitism.

Objective:To explore the efficacy and safety of in-class transition from proteasome inhibitor bortezomib to ixazomib in the treatment of newly-treated patients with multiple myeloma (MM).Methods:The clinical data of 63 newly-treated MM patients in Shenzhen Second People's Hospital from January 2018 to December 2020 were retrospectively analyzed. They were divided into transition group (23 cases) and bortezomib group (40 cases). Both groups were treated with bortezomib-containing regimen as the first-line treatment regimen. In case of intolerable adverse reactions, patients in the transition group were treated with ixazomib instead of bortezomib, while the patients in the bortezomib group did not undergo drug transition. The curative effect and progression-free survival (PFS) were compared between the two groups.Results:In the transition group, the overall response rate (ORR) before in-class transition was 95.7% (22/23), the rate of ≥ very good partial remission (VGPR) was 52.2% (12/23); the ORR after transition was 95.7% (22/23), and the rate of ≥ VGPR was 82.6% (19/23). In the bortezomib group, ORR was 90.0% (36/40), and the rate of ≥ VGPR was 72.5% (29/40). There was no significant difference in ORR and the rate of ≥VGPR between the two groups ( χ2 = 0.64, P=0.424; χ2 = 0.82, P = 0.364). The median number of cycles of PI therapy in the transition group was 9, and the median PFS time was not reached. The median number of cycles of PI therapy in the bortezomib group was 7.5, and the median PFS time was 30.0 months (95% CI 19.1-40.9 months), there was no significant difference in PFS between the two groups ( P = 0.275). In the bortezomib group, 12 patients discontinued bortezomib due to adverse reactions, the median PFS time was 20.0 months (95% CI 12.6-27.4 months), and the PFS of patients who discontinued PI in the transition group and the bortezomib group was compared, the difference was statistically significant ( P = 0.043). In the transition group, 21 patients (21/23, 91.3%) developed peripheral neuropathy, and the incidence of ≥grade 3 adverse reactions was 13.0% (3/23); in the bortezomib group, 22 patients (22/40, 55.0%) developed peripheral neuropathy, and the incidence of ≥grade 3 adverse reactions was 12.5% (5/40). Conclusions:For newly-treated MM patients, the transition from bortezomib to ixazomib can improve the depth of remission and reduce the recurrence caused by the discontinuation of PI.

ObjectiveTo investigate the influence of endoplasmic reticulum stress (ERS) on some inflammatory mediators during the progression of hepatic alveolar echinococcosis (HAE) and its clinical significance. MethodsA total of 15 patients with HAE who underwent partial liver resection in Qinghai University Affiliated Hospital from June 2018 to September 2019 were enrolled, and the marginal zone of HAE lesion was resected as AE group; 15 normal liver tissue samples collected during the same period of time were selected as control group. Western blot and qRT-PCR were used to measure the protein and mRNA expression of protein kinase R-like ER kinase (PERK), CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, and glucose-regulated protein-78 (GRP-78), and q-PCR was used to measure the mRNA expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor (TNF). The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the t-test was used for comparison of normally distributed continuous data between two groups; a Pearson correlation analysis was performed to investigate the correlation between two variables. ResultsCompared with the control group, the AE group had significantly higher protein expression levels of PERK, CHOP, caspase-12, and GRP78 (U=4.165, 3.461, 2.577, and 3.344, all P＜0.001) and their mRNA expression levels (t= 34003, 4.461, 53.573, and 55.224, all P＜0.001). The AE group had significantly higher mRNA expression levels of IL-1β, IL-6, and TNF than the control group (t=6.090, 12.578, and 53.573, all P＜0.001). The protein expression levels of PERK, CHOP, caspase-12, and GRP-78 were positively correlated with the mRNA expression levels of IL-1β, IL-6, and TNF (all r＞0.700, all P≤0.05). ConclusionPositive correlation is observed between the activation of ERS and inflammatory mediators in HAE, and excessive activation of ERS can change the secretion of several inflammatory mediators to exacerbate liver injury, while further studies are needed to clarify the specific mechanism.

Hypertrophic cardiomyopathy (HCM) is a cardiomyopathy characterized by non-secondary asymmetric hypertrophy of the ventricle, most of which manifests as autosomal dominant inheritance, and it is the main cause of sudden death in young athletes. In recent years, HCM has attracted much attention in epidemiology and molecular mechanism of pathogenicity. This article reviews the epidemiology, pathogenesis and clinical manifestations of HCM.