Rapid identification of early infections in febrile patients after CD19 target CAR-T cell therapy for B-cell malignancies.

BACKGROUND: CD19-targeted chimeric antigen receptor T (CAR-T) cell therapy stands out as a revolutionary intervention, exhibiting remarkable remission rates in patients with refractory/relapsed (R/R) B-cell malignancies. However, the potential side effects of therapy, particularly cytokine release syndrome (CRS) and infections, pose significant challenges due to their overlapping clinical features. Promptly distinguishing between CRS and infection post CD19 target CAR-T cell infusion (CTI) remains a clinical dilemma. Our study aimed to analyze the incidence of infections and identify key indicators for early infection detection in febrile patients within 30 days post-CTI for B-cell malignancies. METHODS: In this retrospective cohort study, a cohort of 104 consecutive patients with R/R B-cell malignancies who underwent CAR-T therapy was reviewed. Clinical data including age, gender, CRS, ICANS, treatment history, infection incidence, and treatment responses were collected. Serum biomarkers procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) levels were analyzed using chemiluminescent assays. Statistical analyses employed Pearson's Chi-square test, t-test, Mann-Whitney U-test, Kaplan-Meier survival analysis, Cox proportional hazards regression model, Spearman rank correlation, and receiver operating characteristic (ROC) curve analysis to evaluate diagnostic accuracy and develop predictive models through multivariate logistic regression. RESULTS: In this study, 38 patients (36.5%) experienced infections (30 bacterial, 5 fungal, and 3 viral) within the first 30 days of CAR T-cell infusion. In general, bacterial, fungal, and viral infections were detected at a median of 7, 8, and 9 days, respectively, after CAR T-cell infusion. Prior allogeneic hematopoietic cell transplantation (HCT) was an independent risk factor for infection (Hazard Ratio [HR]: 4.432 [1.262-15.565], P = 0.020). Furthermore, CRS was an independent risk factor for both infection ((HR: 2.903 [1.577-5.345], P < 0.001) and severe infection (9.040 [2.256-36.232], P < 0.001). Serum PCT, IL-6, and CRP were valuable in early infection prediction post-CAR-T therapy, particularly PCT with the highest area under the ROC curve (AUC) of 0.897. A diagnostic model incorporating PCT and CRP demonstrated an AUC of 0.903 with sensitivity and specificity above 83%. For severe infections, a model including CRS severity and PCT showed an exceptional AUC of 0.991 with perfect sensitivity and high specificity. Based on the aforementioned analysis, we proposed a workflow for the rapid identification of early infection during CAR-T cell therapy. CONCLUSIONS: CRS and prior allogeneic HCT are independent infection risk factors post-CTI in febrile B-cell malignancy patients. Our identification of novel models using PCT and CRP for predicting infection, and PCT and CRS for predicting severe infection, offers potential to guide therapeutic decisions and enhance the efficacy of CAR-T cell therapy in the future.

Predictive value of the World falls guidelines algorithm within the AGELESS-MELoR cohort.

AIM: The World Falls Guidelines (WFG) Task Force published a falls risk stratification algorithm in 2022. However, its adaptability is uncertain in low- and middle-income settings such as Malaysia due to different risk factors and limited resources. We evaluated the effectiveness of the WFG risk stratification algorithm in predicting falls among community-dwelling older adults in Malaysia. METHODS: Data from the Malaysian Elders Longitudinal Research subset of the Transforming Cognitive Frailty into Later-Life Self-Sufficiency cohort study was utilized. From 2013-2015, participants aged ≥55 years were selected from the electoral rolls of three parliamentary constituencies in Klang Valley. Risk categorisation was performed using baseline data. Falls prediction values were determined using follow-up data from wave 2 (2015-2016), wave 3 (2019) and wave 4 (2020-2022). RESULTS: Of 1,548 individuals recruited, 737 were interviewed at wave 2, 858 at wave 3, and 742 at wave 4. Falls were reported by 13.4 %, 29.8 % and 42.9 % of the low-, intermediate- and high-risk groups at wave 2, 19.4 %, 25.5 % and 32.8 % at wave 3, and 25.8 %, 27.7 % and 27.0 % at wave 4, respectively. At wave 2, the algorithm generated a sensitivity of 51.3 % (95 %CI, 43.1-59.2) and specificity of 80.1 % (95 %CI, 76.6-83.2). At wave 3, sensitivity was 29.4 % (95 %CI, 23.1-36.6) and specificity was 81.6 % (95 %CI, 78.5-84.5). At wave 4, sensitivity was 26.0 % (95 %CI, 20.2-32.8) and specificity was 78.4 % (95 %CI, 74.7-81.8). CONCLUSION: The algorithm has high specificity and low sensitivity in predicting falls, with decreasing sensitivity over time. Therefore, regular reassessments should be made to identify individuals at risk of falling.

Distribution of oxygen-containing functional groups on defective graphene: properties engineering and Li adsorption.

In this study, the distribution of oxygen-containing functional groups on graphene with vacancies and topological defects was systematically investigated using advanced computational methods and the structure models for multi-defect graphene oxides (GOs) were proposed. All potential adsorption sites were considered through an automated structure generation program to identify energetically favorable structures. Unlike the pristine graphene surface where oxygen-containing functional groups always aggregate with each other, we observed a tendency for them to preferentially adsorb near defects. Furthermore, they may also be distributed on the same side or both sides of the defective graphene. These multi-defect GOs can exhibit either metallic or semiconducting properties. Notably, upon adsorbing the same oxygen-containing functional groups onto the surface of defective graphene, their electronic characteristics become homogeneous. The coexistence of vacancy/topological defects and oxygen-containing functional groups within the graphene lattice introduces intriguing mechanical anisotropic properties to graphene, including the uncommon negative Poisson's ratio. Additionally, these materials exhibit anisotropic optical behavior, displaying heightened absorption within the infrared and visible regions compared to pristine graphene. Finally, it is found that Li atoms are adsorbed stably on the surfaces of multi-defect GOs via the formation of LinO/LimOH clusters. The research findings presented in this paper, encompassing the development of structural models for multi-defect GOs, could provide crucial insights into the properties and potential applications of graphene oxides.

Comparison of Computed Tomography and Clinical Features Between Patients Infected with the SARS-CoV-2 Omicron Variant and the Original Strain.

Purpose: To investigate potential differences in clinical and computed tomography (CT) features between patients with the SARS-CoV-2 Omicron variant and the original strain. Patients and Methods: This retrospective study included 69 hospitalized patients infected with Omicron variant from November to December 2022, and 96 hospitalized patients infected with the original strain from February to March 2020 in Chongqing, China. The clinical features, CT manifestations, degrees of lung involvement in different stages on CT, and imaging changes after the reverse-transcription polymerase chain reaction (RT-PCR) results turned negative were compared between the two groups. Results: For clinical features, patients with Omicron were predominantly old people and females, without manifestation of any clinical symptoms, who had low serum levels of C-reactive protein and procalcitonin. Shorter interval from symptoms onset to initial CT scan was observed in Omicron patients compared to patients with the original strain (all P < 0.05). For CT features, patients with Omicron were more likely to present with round-like opacities and tree-in-bud pattern (all P < 0.05), but less likely to exhibit a diffuse distribution, patchy and linear opacities, as well as vascular enlargement pattern (all P < 0.05). The Omicron group was more susceptible to exhibiting lower CT involvement scores in each stage (all P < 0.05) and imaging progression after the RT-PCR results turned negative (P < 0.001). Conclusion: Patients infected with the Omicron variant exhibited less severe changes on chest CT compared to those infected with the original strain. Furthermore, imaging progression under low viral load conditions was more common in patients with Omicron than in those with the original strain.

Accumulation of circulating myeloid-derived suppressor cell subsets: predicting poor clinical efficacy and prognosis through T cell suppression in non-Hodgkin's lymphoma.

Myeloid-derived suppressor cells (MDSCs) are implicated in the regulation of immune responses closely associated with poor clinical outcomes in cancer. However, the MDSC subtypes in non-Hodgkin's lymphoma (NHL) have not been systematically investigated. So, we investigated the percentage of MDSC subsets in 78 newly diagnosed NHL patients by flow cytometry. The results showed that all MDSC subsets increased in NHL patients compared with healthy donors. Notably, MDSCs, monocytic MDSCs, and CD14 + CD66b + MDSCs significantly increased in NHL patients compared with those with lymphadenitis donors. polymorphonuclear MDSCs (PMN-MDSCs), early-stage MDSCs (e-MDSCs), and the International Prognostic Index were independent risk factors for poor clinical efficacy and were involved in constructing the nomogram for predicting clinical efficacy. Progression-free survival (PFS) was significantly shorter in patients with high level of MDSC subsets, and PMN-MDSCs emerged as an independent prognostic factor for PFS. PMN-MDSCs, e-MDSCs, and the International Prognostic Index were involved in constructing the nomogram for predicting PFS. Patients with a higher percentage of MDSCs, PMN-MDSCs, e-MDSCs, and CD14 + CD66b + MDSCs experienced a shorter overall survival compared with those with lower percentages. In addition, research on mechanisms found that T cell function was suppressed and mediated by the expansion of MDSCs via involving arginase-1 and interleukin-10 in vitro and in vivo. In conclusion, our study demonstrates that the increased circulating MDSC subsets predict poor clinical efficacy and prognosis in NHL, potentially involving T cell suppression through MDSC subset expansion. These findings indicate the potential of MDSC subsets as comprehensive diagnostic, prognostic biomarkers, and therapeutic targets for NHL.

Dense arrangement of crown ethers in graphene: novel graphitic carbon oxides with enhanced optoelectronic properties.

Incorporating crown ethers into a graphene lattice presents an efficient means of tuning its properties and expanding its range of potential applications. This study employed density functional theory calculations to introduce a series of novel graphitic carbon oxides through the dense arrangement of crown ethers featuring varying cavity sizes within the graphene structure. These newly developed graphitic carbon oxides exhibit thermodynamic and dynamic stability. They also manifest improved stability relative to previously reported graphene oxides with similar oxygen content. Notably, a robust linear relationship is observed between the cohesive energies and the proportion of oxygen atoms. The electronic properties of these graphitic carbon oxides span a spectrum of characteristics, including semi-metallic, metallic, and semi-conducting behavior. Their calculated band gaps range from 0.11 eV to 4.38 eV. Specifically, our analysis reveals that C6G-1, characterized by its largest crown ether-like nanopore with six oxygen atoms, holds potential as a material for photocatalytic water splitting. Moreover, these materials exhibit anisotropic optical properties, showcasing a significant enhancement in absorption within the infrared and visible regions relative to pristine graphene. Given the successful experimental synthesis of crown ether in graphene, we anticipate that our findings will contribute to the widespread utilization of graphene derivatives in low-dimensional electronic, catalytic, and optical devices.

Role of the ortho-bridge system in the length unstable subtrochanteric femur fracture in school going children: a retrospective clinical study of 19 cases.

Background: Treating subtrochanteric femur fractures in pediatric patients remains challenging, and an optimal fixation device has yet to be established. This study aimed to asess the clinical and radiological outcomes of Ortho-Bridge System (OBS) treatment for length-unstable subtrochanteric femur fractures in children aged 5-16 years. Methods: We conducted a retrospective review of pediatric patients with subtrochanteric femur fractures treated with OBS between January 2018 and December 2021. The study included 19 children (12 boys, 7 girls) with an average age of 10.4 ± 2.6 years. Two of the patients had pathological fractures associated with aneurysmal bone cyst. Demographic information, mechanism of accident, fracture type, associated neurovascular injuries, surgical duration and blood loss, were collected from the hospital database. Time to union and postoperative complications were recorded. Clinical and radiological outcomes were assessed using the Harris scoring system at the latest follow-up. Results: Injuries resulted from vehicle accidents in 10 patients (52.6%), falls over 3 meters in height in 3 patients (15.8%), and sports-related injuries in 6 patients (31.6%). The average patient weight was 41.5 kg (range: 21-78). Of the fractures, 14 (73.7%) were complex, and 5 (26.3%) were spiral. The average surgical duration was 111 min (range: 90-180), and the average surgical blood loss was 134 ml (range: 70-300). The mean time to union was 12.7 weeks (range: 8-16). No cases of infection, malunion, implant failure, or femoral head osteonecrosis were reported. Leg length discrepancy of 10 mm was observed in one patient. All patients achieved excellent results according to the Harris scoring system. Conclusion: This study suggests that the OBS may serve as an effective alternative fixation option for managing length-unstable subtrochanteric femur fractures in school-aged children.

Overexpression of Grapevine VyTRXy Improves Drought Tolerance by Maintaining Photosynthesis and Enhancing the Antioxidant and Osmolyte Capacity of Plants.

Drought stress profoundly affects plant growth and development, posing a significant challenge that is extensively researched in the field. Thioredoxins (TRXs), small proteins central to redox processes, are crucial to managing both abiotic and biotic stresses. In this research, the VyTRXy gene, cloned from wild Yanshan grapes, was validated as a functional TRX through enzyme activity assays. VyTRXy was found to bolster photosynthesis, augment levels of osmotic regulators, stimulate antioxidant enzyme activities, and strengthen drought resilience in transgenic plants. These enhancements were evidenced by higher survival rates, optimized photosynthetic metrics, increased proline levels, augmented chlorophyll concentration, reduced electrolyte leakage, and decreased malondialdehyde and hydrogen peroxide (H2O2) levels. Furthermore, there was a surge in the activities of enzymes such as catalase, ascorbate peroxidase, glutathione peroxidase, dehydroascorbate reductase, and glutathione reductase, along with an increased expression of TRX peroxidase. Notably, under drought stress, there was a marked elevation in the expression of stress-responsive genes, including the adversity stress-inducible expression gene (NtRD29A) and DRE-binding protein (NtDREB), in transgenic tobacco. This investigation is pivotal in the quest for drought-resistant grapevine varieties and provides significant insights into the molecular functionality of VyTRXy in enhancing grapevine drought tolerance.

Global, but not chondrocyte-specific, MT1-MMP deficiency in adult mice causes inflammatory arthritis.

Membrane-type I metalloproteinase (MT1-MMP/MMP14) plays a key role in various pathophysiological processes, indicating an unaddressed need for a targeted therapeutic approach. However, mice genetically deficient in Mmp14 show severe defects in development and growth. To investigate the possibility of MT1-MMP inhibition as a safe treatment in adults, we generated global Mmp14 tamoxifen-induced conditional knockout (Mmp14kd) mice and found that MT1-MMP deficiency in adult mice resulted in severe inflammatory arthritis. Mmp14kd mice started to show noticeably swollen joints two weeks after tamoxifen administration, which progressed rapidly. Mmp14kd mice reached a humane endpoint 6 to 8 weeks after tamoxifen administration due to severe arthritis. Plasma TNF-α levels were also significantly increased in Mmp14kd mice. Detailed analysis revealed chondrocyte hypertrophy, synovial fibrosis, and subchondral bone remodeling in the joints of Mmp14kd mice. However, global conditional knockout of MT1-MMP in adult mice did not affect body weight, blood glucose, or plasma cholesterol and triglyceride levels. Furthermore, we observed substantial expression of MT1-MMP in the articular cartilage of patients with osteoarthritis. We then developed chondrocyte-specific Mmp14 tamoxifen-induced conditional knockout (Mmp14chkd) mice. Chondrocyte MT1-MMP deficiency in adult mice also caused apparent chondrocyte hypertrophy. However, Mmp14chkd mice did not exhibit synovial hyperplasia or noticeable arthritis, suggesting that chondrocyte MT1-MMP is not solely responsible for the onset of severe arthritis observed in Mmp14kd mice. Our findings also suggest that highly cell-type specific inhibition of MT1-MMP is required for its potential therapeutic use.

Contrast-Enhanced Ultrasonography for Transabdominal and Transrectal Ultrasound in Staging Cervical Cancer: A Reliability Study.

OBJECTIVE: This retrospective study aimed to evaluate the consistency of transrectal contrast-enhanced ultrasonography (TR-CEUS) with post-operative pathology and the value of contrast-enhanced ultrasonography (CEUS) in staging surgically treated cervical cancer when combined with conventional ultrasonography (US). METHODS: From October 2020 to March 2023, hospitalized patients with stage IB and II cervical cancer confirmed by total hysterectomy were consecutively enrolled. The standard images of US and CEUS by transabdominal (TA-US/CEUS) and transrectal (TR-US/CEUS) approaches and magnetic resonance imaging (MRI) were acquired, on which the size and stage of the tumors were evaluated, and the consistency of results with the pathological specimen was analyzed. RESULTS: Thirty-nine patients with cervical cancer were finally enrolled in this study. The results showed that CEUS significantly improved the reliability of TA-US in evaluating tumor diameter; the intraclass correlation coefficient (ICC) was from 0.672 to 0.735. TR-US indicated good reliability with or without the addition of CEUS (ICC = 0.796 and 0.780). In terms of tumor staging, CEUS improved the consistency of transabdominal (weighted κ values from 0.689 to 0.731) and transrectal staging of tumors (κ from 0.758 to 0.785), and the staging of TR-US combined with TR-CEUS had the highest consistency with post-operative results, similar to MRI (κ, respectively 0.785 and 0.789). CEUS can reflect the heterogeneity of the tumor. Heterogeneous enhancement and perfusion defects were more common in >2 cm cervical cancer (50%, 20/40 and 52.5%, 21/40), respectively, and perfusion defects were more common in moderately to poorly differentiated tumors (66.67%, 20/30). CONCLUSION: For stage IB and IIA cervical cancer, CEUS can aid in assessing the International Federation for Gynecology and Obstetrics staging of tumors alongside TA-US and TR-US. The combination of TR-US and TR-CEUS has shown good consistency with pathology in the staging of cervical cancer, comparable to that of MRI.

Novel mutations in TRIP13 lead to female infertility with oocyte maturation arrest.

Oocyte maturation arrest (OMA) refers to a rare clinical phenomenon of oocyte maturation disorder caused by abnormal meiosis, which is also one of the primary causes of female infertility. The clinical manifestations of these patients are often characterized with failure to obtain mature oocytes after repeated ovulation stimulation and/or induced in vitro maturation. To date, mutations in PATL2, TUBB8 and TRIP13 have been demonstrated to be associated with OMA, but studies on the genetic-based factors and mechanisms of OMA are still incomplete. In this study, peripheral blood from 35 primary infertile women characterized with recurrent OMA during assisted reproductive technology (ART) were subjected to whole-exome sequencing (WES). By using Sanger sequencing and co-segregated analysis, we identified four pathogenic variants in TRIP13. Proband 1 had a homozygous missense mutation of c.859A>G appeared on the 9th exon, which resulted in substitution of Ile287 to valine (p.Ile287Val); proband 2 had a homozygous missense mutation of c.77A>G on the 1st exon, which resulted in substitution of His26 to arginine (p.His26Arg); and proband 3 had compound heterozygous mutations of c.409G>A and c.1150A>G on the 4th and 12th exon, which resulted in the substitutions of Asp137 to asparagine (p.Asp137Asn) and Ser384 to glycine (p.Ser384Gly) in the encoded protein respectively. Three of these mutations have not been reported previously. Further, transfection of plasmids harboring the respective mutated TRIP13 in HeLa cells resulted in changes in TRIP13 expression and abnormal cell proliferation as demonstrated by western blotting and cell proliferation assay respectively. This study further summarizes the TRIP13 mutations reported previously and expands the mutation spectrum of TRIP13 pathogenic variants, thereby providing a valuable reference for further research on the pathogenic mechanism of OMA associated with TRIP13 mutations.

Integrated mRNA and miRNA transcriptome analysis of grape in responses to salt stress.

Salt stress is an important factor which may negatively affect plant growth and development. High concentrations of Na+ ions can destroy the ion balance in plant somatic cells, as well as destroying cell membranes and forming a large number of reactive oxygen species (ROS) and other damage mechanisms. However, plants have evolved numerous defense mechanisms in response to the damages caused by salt stress conditions. Grape (Vitis vinifera L.), a type of economic crop, is widely planted throughout the world. It has been found that salt stress is an important factor affecting the quality and growth of grape crops. In this study, a high-throughput sequencing method was used to identify the differentially expressed miRNAs and mRNAs in grapes as responses to salt stress. A total of 7,856 differentially expressed genes under the salt stress conditions were successfully identified, of which 3,504 genes were observed to have up-regulated expressions and 4,352 genes had down-regulated expressions. In addition, this study also identified 3,027 miRNAs from the sequencing data using bowtie and mireap software. Among those, 174 were found to be highly conserved, and the remaining miRNAs were less conserved. In order to analyze the expression levels of those miRNAs under salt stress conditions, a TPM algorithm and DESeq software were utilized to screen the differentially expressed miRNAs among different treatments. Subsequently, a total of thirty-nine differentially expressed miRNAs were identified, of which fourteen were observed to be up-regulated miRNAs and twenty-five were down-regulated under the salt stress conditions. A regulatory network was built in order to examine the responses of grape plants to salt stress, with the goal of laying a solid foundation for revealing the molecular mechanism of grape in responses to salt stress.

Novel Insights of ANGPTL-3 on Modulating Cholesterol Efflux Capacity Induced by HDL Particle.

BACKGROUND: Angiopoietin-like protein 3 (ANGPTL-3) modulates lipid metabolism and the risk of coronary artery disease (CAD), especially stable angina (SA), via suppressing lipoprotein lipase (LPL). However, whether there are other mechanisms is not elucidated yet. The current research explored the modulatory roles of ANGPTL-3 on high-density lipoprotein (HDL), which further affects atherosclerotic development. METHODS: A total of 200 individuals were enrolled in the present study. Serum ANGPTL-3 levels were detected via enzyme-linked immunosorbent assays (ELISA). Cholesterol efflux capacity induced by HDL particles was detected through H3-cholesterol loading THP-1 cell. RESULTS: The serum ANGPTL-3 levels presented no significant discordance between the SA group and the non-SA group, whereas the serum ANGPTL-3 levels in type 2 diabetes mellitus (T2DM) group were significantly elevated compared with those in the non-T2DM group [428.3 (306.2 to 736.8) ng/ml vs. 298.2 (156.8 to 555.6) ng/ml, P <0.05]. Additionally, the serum ANGPTL-3 levels were elevated in patients with low TG levels compared to those in patients with high TG levels [519.9 (377.6 to 809.0) ng/ml vs. 438.7 (329.2 to 681.0) ng/ml, P <0.05]. By comparison, the individuals in the SA group and T2DM group presented decreased cholesterol efflux induced by HDL particles [SA: (12.21±2.11)% vs. (15.51±2.76)%, P <0.05; T2DM: (11.24±2.13)% vs. (14.65±3.27)%, P <0.05]. In addition, the serum concentrations of ANGPTL-3 were inversely associated with the cholesterol efflux capacity of HDL particles (r=-0.184, P <0.05). Through regression analysis, the serum concentrations of ANGPTL-3 were found to be an independent modulator of the cholesterol efflux capacity of HDL particles (standardized ß=-0.172, P <0.05). CONCLUSION: ANGPTL-3 exhibited a negative modulatory function on cholesterol efflux capacity induced by HDL particles.

Genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021 / 中华预防医学杂志

Objective: To characterize the prevalence and genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021. Methods: Based on the Shenzhen Infectious Diarrhea Surveillance System, acute diarrheal patients were actively monitored in sentinel hospitals from 2013 to 2021. Whole-genome sequencing (WGS) of Vibrio parahaemolyticus isolates was performed, and the genomic population structure, serotypes, virulence genes and multilocus sequence typing were analyzed. Outbreak clusters from 2019 to 2021 were explored based on single-nucleotide polymorphism analysis. Results: A total of 48 623 acute diarrhea cases were monitored in 15 sentinel hospitals from 2013 to 2021, and 1 135 Vibrio parahaemolyticus strains were isolated, with a positive isolation rate of 2.3%. Qualified whole-genome sequencing data of 852 isolates were obtained. Eighty-nine serotypes, 21 known ST types and 5 new ST types were identified by sequence analysis, and 93.2% of strains were detected with toxin profile of tdh+trh-. 8 clonal groups (CGs) were captured, with CG3 as the absolute predominance, followed by CG189. The CG3 group was dominated by O3:K6 serotype and ST3 sequence type, while CG189 group was mainly O4:KUT, O4:K8 serotypes and ST189a and ST189 type. A total of 13 clusters were identified, containing 154 cases. About 30 outbreak clusters with 29 outbreak clusters caused by CG3 strains from 2019 to 2021. Conclusion: Vibrio parahaemolyticus is a major pathogen of acute infectious diarrhea in Shenzhen City, with diverse population structures. CG3 and CG189 have been prevalent and predominant in Shenzhen City for a long time. Scattered outbreaks and persistent sources of contamination ignored by traditional methods could be captured by WGS analysis. Tracing the source of epidemic clone groups and taking precise prevention and control measures are expected to significantly reduce the burden of diarrhea diseases caused by Vibrio parahaemolyticus infection in Shenzhen City.

Analysis of the influencing factors of vault after the implantation of posterior chamber-phakic refractive lens for patients with super high myopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the influencing factors of vault after the posterior chamber phakic refractive lens(PC-PRL)implantation for patients with super high myopia.METHODS: Retrospective case study. A total of 40 patients with super high myopia(77 eyes)who underwent PC-PRL implantation in the Haixiang Eye Hospital from January 2019 to January 2021 were selected. They were followed up for at least 2a, postoperative anterior segment parameters, such as the uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), central anterior chamber depth(ACD), anterior chamber volume(ACV), anterior chamber angle(ACA), lens thickness and vault were evaluated, and then the influencing factors of postoperative vault were analyzed.RESULTS: The UCVA and BCVA of the patients significantly improved after PC-PRL implantation(P&#x003C;0.001). Average safety index(postoperative BCVA/preoperative BCVA)was 1.36±0.32, and average effective index(postoperative UCVA/preoperative BCVA)was 1.23±0.31 in 2a after surgery. The vault in 2a after surgery was correlated with preoperative ACD, ACV, ACA and lens thickness, and the preoperative ACV and lens thickness had significant impact on vault in 2a after surgery.CONCLUSIONS: The PC-PRL implantation is safe and effective in super high myopia, and it can significantly improve visual acuity. Furthermore, preoperative ACV and lens thickness are important influencing factors of postoperative vault.

Alterations in dendritic length and branch and K / 解剖学报

Objective To study the morphology of olfactory bulb(OB) neurons and the change of related proteins, and explore the causes of olfactory dysfuction in Alzheimer' s disease(AD). Methods Golgi-Cox staining technique was used to evaluate the morphological changes of neurons in the OB and anterior piriform cortex (aPC) of APP/PS1 AD model mice. The morphology of neurons was determined by Sholl analysis. Western blotting was used to evaluate the levels of protein expression. Results The results of Golgi-Cox showed that the dendrite length and branch number reduced significantly in the OB neurons of 3-5-month-old APP/PS1 mice, an age that the mice did not show the pathological characteristics and cognitive impairment of AD. Western blotting analysis showed that levels of potassium chloride cotransporter 2(KCC2), a potassium chloride transporter crucial for neuronal morphology and synaptic function, decreased significantly in the OB of 3-5-month-old APP/PS1 mice. Conclusion Abnormal neuronal morphology and KCC2 signal might be the basis of early olfactory dysfunction in AD. Thus, maintaining normal KCC2 signal may be one of the keys to intervene the olfactory abnormalities in the early stage of AD.

Metabolomic Profiling and Assessment of Phenolic Compounds Derived from Vitis davidii Foex Cane and Stem Extracts

Phenolic extracts from berry seeds have been extensively studied for their health benefits. However, few studies have been conducted on the effects of phenolic extracts from Vitis L. canes and berry stems. The Chinese spine grape (V. davidii Foex) is an important and widely distributed wild species of Vitis L. The present study explored the metabolomic profile and evaluated the antioxidant activity of phenolic compounds in extracts from V. davidii Foex. canes and stems, with a focus on their role in preventing DNA damage caused by free radicals and inhibiting the growth of breast (MCF-7) and cervical (HeLa) cancer cells. Total phenolic compounds in the dried berry stems of spine grapes were higher than that in vine canes. Analysis of the extracts showed that proanthocyanins, epicatechin, catechin, and phenolic acid were the main phenolic compounds in V. davidii Foex, but in higher quantities in berry stems than in vine canes. However, trans-resveratrol and kaempferol 3-O-glucoside were present in the vine canes but not in the berry stems. Antioxidant analysis by FRAP and ABTS showed that extracts from berry stems and vine canes had a higher antioxidant activity than thinned young fruit shoots before flowering, leaves, peel, pulp, and seeds in V. davidii Foex. Moreover, the antioxidant activity of extracts from berry stems was higher than that in other grape species, except for muscadine. In vitro analyses further showed that the extracts significantly increased H2O2 scavenging ability and conferred a protective effect against DNA damage. Furthermore, a low concentration of phenolic compounds in extracts from the vine canes and berry stems of spine grapes inhibited the proliferation of the MCF-7 and Hela cancer cells. These research results provided some important useful information for the exploitation of V. davidii Foex canes and berry stems and indicated that canes and stems of V. davidii Foex had good antioxidant properties, anticancer activity and prevented DNA damage, providing evidence for medical utilization of V. davidii Foex.

Anticholinergics and falls in older adults.

INTRODUCTION: The use of medications with anticholinergic (ACh) properties is associated with numerous adverse effects especially in older adults. Emerging evidence suggests the presence of long-term effects with ACh use. AREAS COVERED: Our article presents an overview of ACh effects and falls in older individuals including examination of emerging evidence on ACh use and cumulative exposure on short-term and long-term falls risk. The databases CINAHL, MEDLINE, EMBASE, and Web of Science were searched for articles published from January 2002 to December 2021. EXPERT OPINION: Anticholinergic side effects include muscle weakness, blurred vision, and mental confusion which are likely to lead to increased falls risk. Many commonly used medications such as beta-blockers, calcium-channel blockers, and antihistamines are now known to have mild ACh properties. With polypharmacy now considered unavoidable in older patients, the cumulative effects of the use of multiple drugs with mild ACh properties may also lead to increased falls risk. The relationship between ACh drugs and falls may also be irreversible as ACh effects may extend beyond the period of drug use, due to cognitive and physical deconditioning following the initial exposure to ACh drugs. Future long-term studies with accurate quantification of cumulative ACh exposure and measurement of actual falls outcomes are urgently required.