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Muhammad Saif Ur Rahman,1 Ling Zhang,2 Lingyan Wu,1 Yuqiong Xie,1 Chunchun Li,1 Jiang Cao1 1Clinical Research Center, 2Cardiovascular Key Laboratory of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China Abstract: Severe side effects are major problems with chemotherapy of gastric cancer (GC). These side effects can be reduced by using sensitizing agents in combination with therapeutic drugs. In this study, the low/nontoxic dosage of glaucocalyxin B (GLB) was used with other DNA linker agents mitomycin C (MMC), cisplatin (DDP), or cyclophosphamide (CTX) to treat GC cells. Combined effectiveness of GLB with drugs was determined by proliferation assay. The molecular mechanisms associated with cell proliferation, migration, invasion, cell cycle, DNA repair/replication, apoptosis, and autophagy were investigated by immunoblotting for key proteins involved. Cell cycle and apoptosis analysis were performed by flow cytometry. Reactive oxygen species level was also examined for identification of its role in apoptosis. Proliferation assay revealed that the addition of 5 µM GLB significantly sensitizes gastric cancer SGC-7901 cells to MMC, DDP, and CTX by decreasing half-maximal inhibitory concentration (IC50) by up to 75.40%±5%, 45.10%±5%, and 52.10%±5%, respectively. GLB + drugs decreased the expression level of proteins involved in proliferation and migration, suggesting the anticancer potential of GLB + drugs. GLB + MMC, GLB + CTX, and GLB + DDP arrest the cells in G0/G1 and G1/S phase, respectively, which may be the consequence of significant decrease in the level of enzymes responsible for DNA replication and telomerase shortening. Combined use of GLB with these drugs also induces DNA damage and apoptosis by activating caspase/PARP pathways and increased production of reactive oxygen species and increased autophagy in GC cells. GLB dosage sensitizes GC cells to the alkylating agents via arresting the cell cycle and enhancing cell death. This is of significant therapeutic importance in the reduction of side effects associated with these drugs. Keywords: glaucocalyxin B, mitomycin C, cisplatin, cyclophosphamide, DNA linkers, side effects, gastric cancer

Yiqiao Xie,1,* Zhiquan Zhuang,2,* Shu Zhang,1 Zihua Xia,1 De Chen,1 Kaiyan Fan,1 Jialin Ren,1 CuiCui Lin,1 Yanzhong Chen,1 Fan Yang1 1Department of Pharmaceutics, Guangdong Pharmaceutical University, 2Department of Pharmacy, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, People’s Republic of China *These authors contributed equally to this work Purpose: The present study examined the factors affecting the content of impurities of nimodipine (NMP) emulsion and the associated methods of compound protection.Methods: Destructive testing of NMP emulsion and its active pharmaceutical ingredient (API) were conducted, and ultracentrifugation was used to study the content of impurities in two phases. The impurity of NMP was measured under different potential of hydrogen (pH) conditions, antioxidants and pH-adjusting agents.Results: Following destruction, the degradation of NMP notably occurred in the basic environment. The consumption of the pH-adjusting agent NaOH was proportional to the production of impurities since the inorganic base and/or acid promoted the degradation of NMP. The organic antioxidants, notably amino acids with an appropriate length of intermediate chain and electron-donating side group, exhibited improved antioxidant effects compared with inorganic antioxidants. The minimal amount of impurities was produced following addition of 0.04% lysine and 0.06% leucine in the aqueous phase and adjustment of the pH to a range of 7.5–8.0 in the presence of acetic acid solution.Conclusion: NMP was more prone to degradation in an oxidative environment, in an aqueous phase and/or in the presence of inorganic pH-adjusting agents and antioxidants. The appropriate antioxidant and pH-adjusting agent should be selected according to the chemical structure, while destructive testing of the drug is considered to play the optimal protective effect. Keywords: nimodipine emulsion, impurity, destructive testing, ultracentrifugation, antioxida­tion, pH

Objective: To investigate anticoagulation effects of nafamostat mesylate(NM) in sustained low-efficiency dialysis (SLED) and its relevant factors. Methods: Critically ill patients with kidney disease who were admitted to Zhongshan Hospital Affiliated to Fudan University and underwent SLED treatment from May to August 2024 were retrospectively included. Baseline clinical data were collected, and the activated partial thromboplastin time (APTT) and activated clotting time (ACT) were measured at the arterial end, before the filter, and at the venous end two hours post-NM anticoagulation treatment. Patients were categorized into two groups: the anticoagulation achievement group and the anticoagulation non-achievement group, based on the observed clotting status of the filter and venous reservoir following treatment completion. Multivariate logistic regression analysis was employed to identify risk factors influencing the efficacy of NM anticoagulation. Additionally, the receiver operating characteristic (ROC) curve was utilized to ascertain optimal monitoring indicators for NM anticoagulation. Results: A total of 96 patients (64 males and 32 females) aged (60±18) years undergoing SLED were included in the study, with 75 patients in the anticoagulation achievement group and 21 patients in the anticoagulation non-achievement group. No statistically significant differences were observed in baseline characteristics such as age, gender, body weight, baseline liver and kidney function, and platelet count between the two groups (all P >0.05). The proportion of patients with a baseline hematocrit (HCT)>30% was higher in the anticoagulation non-achievement group than that in the achievement group [57.1% (12/21) vs 22.7% (17/75), P =0.009]. The proportion of patients with fibrinogen (Fib)>4 g/L was also higher in the anticoagulation non-achievement group [90.5% (19/21) vs 49.3% (37/75), P <0.001]. The ultrafiltration rate in the anticoagulation achievement group was lower than that in the non-achievement group [232 (182, 353) ml/h vs 478 (289, 691) ml/h, P <0.001], and the NM dose was higher in the achievement group [35 (30, 40) mg/h vs 30 (25, 35) mg/h, P <0.001]. Multivariate logistic regression analysis revealed that high ultrafiltration rate ( OR =1.489, 95% CI : 1.007-2.145, P <0.001), HCT>30% ( OR =6.907, 95% CI : 1.523-18.342, P =0.009), and low albumin level ( OR =0.821, 95% CI : 0.709-0.951, P =0.002) were relevant factors for poor NM efficacy. After 2 hours of NM treatment, the ratio of ACT at the venous/baseline ACT and the ratio of APTT at the venous/baseline APTT in the anticoagulation achievement group were both higher than those in the non-achievement group (both P <0.05). There was a positive correlation between APTT and ACT measured at the venous end 2 hours after NM treatment ( r =0.763, P <0.001). The ROC curve analysis results showed that the area under the curve (AUC) for determining the effectiveness of NM anticoagulation using the ratio of APTT at the venous end to baseline APTT at 2 hours was 0.845 (95% CI : 0.762-0.928, P <0.001), with a cut-off value of 1.78 (sensitivity: 89.8%; specificity: 68.6%). Conclusions: Higher filtration rate, HCT>30% and lower albumin levels are identified as relevant factors for poor NM efficacy. Additionally, the ratio of venous/baseline APTT at 2 h after NM treatment may serve as a predictive indicator for assessing of NM anticoagulation.

Single-atom catalysts (SACs) have been increasingly acknowledged for their performance in sustainable Fenton-like catalysis. However, SACs face a trade-off between activity and stability in peroxymonosulfate (PMS)-based systems. Herein, we design a nano-island encapsulated single cobalt atom (Co SA/Zn.O -ZnO) catalyst to enhance the activity and stability of PMS activation for contaminant degradation via an "island-sea" synergistic effect. In this configuration, small carrier-based ZnO nanoparticles (the "islands") are utilized to confine and stabilize Co single atoms. The expansive ZnO substrate (the "sea") upholds a neutral microenvironment within the reaction system. The Co SA/Zn.O -ZnO/PMS system exhibits a remarkable selectivity in exclusively generating sulfate radicals (SO 4 •- ), leading to a complete removal of various recalcitrant pollutants within a shorter period. Characterized by minimal leaching of active sites, robust catalytic performance, and low-toxicity decontamination, this system proves highly efficient in multiple treatment cycles and complex water matrices. The design effectively breaks the activity-stability trade-off typically associated with SACs., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Rationale: This article summarized the nursing experience of phlebitis caused by intravenous infusion of amphotericin B cholesterol sulfate complex in a patient with myelodysplastic syndrome., Patient Concerns: A 59-year-old man with myelodysplastic syndrome complicated with fungal infection was treated with antifungal therapy., Diagnoses: Patient with myelodysplastic syndrome was diagnosed with secondary phlebitis caused by liposomal amphotericin B., Interventions: The focus of nursing care was to use infrared rays of a specific electromagnetic wave therapy device to treat the patient's phlebitis., Outcomes: After 30 minutes each time, twice a day, the patient's phlebitis was cured after 6 days of continuous use., Lessons: The specific electromagnetic wave therapy can make the phlebitis caused by amphotericin B quickly heal, which is helpful for the smooth implementation of the antifungal treatment program., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To evaluate the efficacy of early goal-directed renal replacement therapy (GDRRT) in patients with severe pneumonia associated acute kidney injury (AKI). Methods: Patients with severe pneumonia and diagnosed with AKI, and underwent GDRRT at Zhongshan Hospital between January 1, 2017 and December 31, 2022 were retrospectively enrolled. All patients were divided into early RRT group and regular RRT group according to fluid status, inflammation progression, and hemodynamics at RRT initiation.The primary endpoint was in-hospital all-cause mortality, and the secondary endpoints included recovery of renal function at discharge, and 90-day and 1-year all-cause mortality. The multivariate Cox regressionwas employed to analyze therelationship between timing of RRT initiation and patient's prognosis. Results: A total of 170 patients aged (71±13) years were enrolled, including 122 males (71.8%). There were 86 and 84 cases in the early and regular RRT groups, respectively. No statistically significant differences of demographic characteristics were detected between the two groups (all P >0.05). At RRT initiation, the patients in the early RRT group displayed a lower percentage of fluid load [2% (1%, 3%) vs 3% (2%, 4%), P <0.001], lower rate of using high-dose of vasoactive agents [11.6% (10/86) vs 40.5% (34/84), P <0.001] and higher rate of radiographic progression within 72 h in the intensive care unit (ICU) [58.1% (50/86) vs 33.3% (28/84), P <0.001] than those in the regular RRT group. The all-cause in-hospital mortality was significantly lower in the early RRT group than that in regular RRT group [37.2% (32/86) vs 67.9% (57/84), P <0.001]. Patients in the early RRT group displayed a significantly higher proportion of complete renal recovery at discharge [44.2% (38/86) vs 7.1% (6/84), P <0.001]. The 90-day [46.5% (40/86) vs 82.1% (69/84), P <0.001] and 1-year [65.1% (56/86) vs 92.9% (78/84), P <0.001] mortality were significantly lower in the early RRT group. Multivariate Cox proportional hazards regression model revealed that the early initiation of GDRRT significantly decreased the risk of in-hospital mortality ( HR =0.57, 95% CI : 0.37-0.88, P =0.011). Conclusion: This study indicates that early GDRRT for the treatment of severe pneumonia-associated AKI based on fluid status, hemodynamics and inflammation progression is associated with reduced hospital mortality and better recovery of renal function.

Bile acids (BAs) play a crucial role in lipid metabolism of children. However, the association between per- and polyfluoroalkyl substance (PFAS) exposure and BAs in children is scarce. To address this need, we selected 252 children from the Maoming Birth Cohort and measured 32 PFAS, encompassing short- and long-chain perfluorocarboxylic acids (PFCAs) and perfluorosulfonic acids (PFSAs) in the cord blood. Additionally, we analyzed nine primary and eight secondary BAs in the serum of three-year-old children. Generalized linear models with FDR-adjusted and Bayesian kernel machine regression (BKMR) were used to explore the associations of individual and mixture effects of PFAS and BAs. We found negative associations between cord blood long-chain PFCAs exposure and serum primary BAs in three-year-old children. For example, one ln-unit (ng/mL) increase of perfluoro-n-tridecanoic acid (PFTrDA), perfluoro-n-undecanoic acid (PFUnDA) and perfluoro-n-decanoic acid (PFDA) were associated with decreased taurochenodeoxycholic acid, with estimated percentage change of -24.28% [95% confidence interval (CI): -36.75%, -9.35%], -25.84% (95% CI: -39.67%, -8.83%), and -22.97% (95% CI: -34.45%, -9.47%) respectively. Notably, the observed associations were more pronounced in children with lower vegetable intake. Additionally, the BKMR model also demonstrated a monotonical decline in primary BAs as the PFAS mixture increased. We provided the first evidence of the association between intrauterine exposure to PFAS and its mixture with BAs in children. Further large-sample-size studies are needed to verify this finding., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Camellia nitidissima Chi is a popular ornamental plant because of its golden flowers, which contain flavonoids and carotenoids. To understand the regulatory mechanism of golden color formation, the metabolites of C. nitidissima petals at five different developmental stages were detected, a proteome map of petals was first constructed via tandem mass tag (TMT) analysis, and the accuracy of the sequencing data was validated via parallel reaction monitoring (PRM)., Results: Nineteen color components were detected, and most of these components were carotenoids that gradually accumulated, while some metabolites were flavonoids that were gradually depleted. A total of 97,647 spectra were obtained, and 6,789 quantifiable proteins were identified. Then, 1,319 differentially expressed proteins (DEPs) were found, 55 of which belong to the flavonoid and carotenoid pathways, as revealed by pairwise comparisons of protein expression levels across the five developmental stages. Notably, most DEPs involved in the synthesis of flavonoids, such as phenylalanine ammonium lyase and 4-coumarate-CoA ligase, were downregulated during petal development, whereas DEPs involved in carotenoid synthesis, such as phytoene synthase, 1-deoxy-D-xylulose-5-phosphate synthase, and β-cyclase, tended to be upregulated. Furthermore, protein‒protein interaction (PPI) network analysis revealed that these 55 DEPs formed two distinct PPI networks closely tied to the flavonoid and carotenoid synthesis pathways. Phytoene synthase and chalcone synthase exhibited extensive interactions with numerous other proteins and displayed high connectivity within the PPI networks, suggesting their pivotal biological functions in flavonoid and carotenoid biosynthesis., Conclusion: Proteomic data on the flavonoid and carotenoid biosynthesis pathways were obtained, and the regulatory roles of the DEPs were analyzed, which provided a theoretical basis for further understanding the golden color formation mechanism of C. nitidissima., (© 2024. The Author(s).)

The success of chimeric antigen receptor (CAR) T cell therapy in treating several hematopoietic malignancies has been difficult to replicate in solid tumors, in part because of T cell exhaustion and eventually dysfunction. To counter T cell dysfunction in the tumor microenvironment, we metabolically armored CAR T cells by engineering them to secrete interleukin-10 (IL-10). We show that IL-10 CAR T cells preserve intact mitochondrial structure and function in the tumor microenvironment and increase oxidative phosphorylation in a mitochondrial pyruvate carrier-dependent manner. IL-10 secretion promoted proliferation and effector function of CAR T cells, leading to complete regression of established solid tumors and metastatic cancers across several cancer types in syngeneic and xenograft mouse models, including colon cancer, breast cancer, melanoma and pancreatic cancer. IL-10 CAR T cells also induced stem cell-like memory responses in lymphoid organs that imparted durable protection against tumor rechallenge. Our results establish a generalizable approach to counter CAR T cell dysfunction through metabolic armoring, leading to solid tumor eradication and long-lasting immune protection., Competing Interests: Competing interests Y.G., L.T. and Y.Z. are inventors on patents related to the technology described in this paper. L.T. and Y.G. are cofounders, share-holders and advisors for Leman Biotech. The interests of L.T. were reviewed and managed by EPFL. The other authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Current cancer immunotherapy predominately focuses on eliciting type 1 immune responses fighting cancer; however, long-term complete remission remains uncommon 1,2 . A pivotal question arises as to whether type 2 immunity can be orchestrated alongside type 1-centric immunotherapy to achieve enduring response against cancer 3,4 . Here we show that an interleukin-4 fusion protein (Fc-IL-4), a typical type 2 cytokine, directly acts on CD8 + T cells and enriches functional terminally exhausted CD8 + T (CD8 + T TE ) cells in the tumour. Consequently, Fc-IL-4 enhances antitumour efficacy of type 1 immunity-centric adoptive T cell transfer or immune checkpoint blockade therapies and induces durable remission across several syngeneic and xenograft tumour models. Mechanistically, we discovered that Fc-IL-4 signals through both signal transducer and activator of transcription 6 (STAT6) and mammalian target of rapamycin (mTOR) pathways, augmenting the glycolytic metabolism and the nicotinamide adenine dinucleotide (NAD) concentration of CD8 + T TE cells in a lactate dehydrogenase A-dependent manner. The metabolic modulation mediated by Fc-IL-4 is indispensable for reinvigorating intratumoural CD8 + T TE cells. These findings underscore Fc-IL-4 as a potent type 2 cytokine-based immunotherapy that synergizes effectively with type 1 immunity to elicit long-lasting responses against cancer. Our study not only sheds light on the synergy between these two types of immune responses, but also unveils an innovative strategy for advancing next-generation cancer immunotherapy by integrating type 2 immune factors., (© 2024. The Author(s).)

Background: Tuberculosis (TB) is a chronic respiratory infectious disease that considerably jeopardizes human health, and there is no effective vaccine suitable for its prevention in the entire population., Aim: To investigate the promotion of medication adherence and disease cognition in patients with drug-resistant (DR-)TB using detailed nursing management., Methods: In total, 114 patients with DR-TB who were diagnosed and treated at our hospital between January 2019 and January 2023 were included in this study. Patients in the control group ( n = 57) were managed with conventional nursing care, while those in the observation group ( n = 57) were managed with detailed nursing care. Medication adherence, disease awareness scores, medication safety, and nursing satisfaction were compared between the two groups after the intervention., Results: The post-intervention medication compliance rate was 91.23% in the observation group and 75.44% in the control group, with the former being 15.79% higher than the latter ( P < 0.05). There was no statistically significant difference in the disease awareness scores between the two groups before the intervention; the disease awareness scores of the observation group were significantly higher than those of the control group after the intervention ( P < 0.05). The incidence of gastrointestinal reactions, joint swelling and pain, hearing loss, electrolyte disorders, and liver and kidney function abnormalities were lower in the observation group than those in the control group. The total nursing satisfaction of the observation group was higher than that of the control group ( P < 0.05)., Conclusion: Implementation of detailed nursing management for patients with DR-TB can effectively improve medication adherence, enhance awareness of the disease, ensure safety of medication, and improve satisfaction with nursing care., Competing Interests: Conflict-of-interest statement: All authors declare no potential conflicting interests related to this paper., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Endometrial cancer (EC) is the sixth most frequent cancer in women worldwide and has higher fatality rates. The pathophysiology of EC is complex, and there are currently no reliable methods for diagnosing and treating the condition. Long non-coding RNA (lncRNA), according to mounting evidence, is vital to the pathophysiology of EC. HOTAIR is regarded as a significant prognostic indicator of EC. ZBTB7A decreased EC proliferation and migration, according to recent studies, however the underlying mechanism still needs to be clarified., Methods: The research utilized RT-qPCR to measure HOTAIR expression in clinical EC tissues and various EC cell lines. Kaplan-Meier survival analysis was employed to correlate HOTAIR levels with patient prognosis. Additionally, the study examined the interaction between ZBTB7A and HOTAIR using bioinformatics tools and ChIP assays. The experimental approach also involved manipulating the expression levels of HOTAIR and ZBTB7A in EC cell lines and assessing the impact on various cellular processes and gene expression., Results: The study found significantly higher levels of HOTAIR in EC tissues compared to adjacent normal tissues, with high HOTAIR expression correlating with poorer survival rates and advanced cancer characteristics. EC cell lines like HEC-1 A and KLE showed higher HOTAIR levels compared to normal cells. Knockdown of HOTAIR in these cell lines reduced proliferation, angiogenesis, and migration. ZBTB7A was found to be inversely correlated with HOTAIR, and its overexpression led to a decrease in HOTAIR levels and a reduction in malignant cell behaviors. The study also uncovered that HOTAIR interacts with ELAVL1 to regulate SOX17, which in turn activates the Wnt/β-catenin pathway, promoting malignant behaviors in EC cells., Conclusion: HOTAIR is a critical regulator in EC, contributing to tumor growth and poor prognosis. Its interaction with ZBTB7A and regulation of SOX17 via the Wnt/β-catenin pathway underlines its potential as a therapeutic target., (© 2024. The Author(s).)

Despite the array of mammalian transgene switches available for regulating therapeutic protein expression in response to small molecules or physical stimuli, issues remain, including cytotoxicity of chemical inducers and limited biocompatibility of physical cues. This study introduces gene switches driven by short peptides comprising eight or fewer amino acid residues. Utilizing a competence regulator (ComR) and sigma factor X-inducing peptide (XIP) from Streptococcus vestibularis as the receptor and inducer, respectively, this study develops two strategies for a peptide-activated transgene control system. The first strategy involves fusing ComR with a transactivation domain and utilizes ComR-dependent synthetic promoters to drive expression of the gene-of-interest, activated by XIP, thereby confirming its membrane penetrability and intracellular functionality. The second strategy features an orthogonal synthetic receptor exposing ComR extracellularly (ComR EXTRA ), greatly increasing sensitivity with exceptional responsiveness to short peptides. In a proof-of-concept study, peptides are administered to type-1 diabetic mice with microencapsulated engineered human cells expressing ComR EXTRA for control of insulin expression, restoring normoglycemia. It is envisioned that this system will encourage the development of short peptide drugs and promote the introduction of non-toxic, orthogonal, and highly biocompatible personalized biopharmaceuticals for gene- and cell-based therapies., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Aim: To describe the outcome of using low-dose laser cycloplasty (LCP) in chronic angle-closure glaucoma (CACG)., Methods: A retrospective case series. Medical charts of CACG patients who underwent LCP in the Eye Hospital of Wenzhou Medical University were reviewed. The main outcomes included intraocular pressure (IOP), the number of glaucoma medication, anterior segment parameters and surgery-related complications., Results: A total of 7 eyes of 7 CACG patients (age 38.9±11.0y) underwent LCP with a mean follow-up of 27.1±13.7mo (range 16-48mo). Following LCP, mean IOP and glaucoma medications decreased from 26.1±6.1 mm Hg with 3.1±1.1 glaucoma medications pre-treatment to 14.9±3.1 mm Hg ( P =0.027) with 0.4±1.1 glaucoma medications ( P =0.001) at final follow-up. The anterior chamber depth (ACD), angle opening distance 500 and trabecular-iris angle increased from 1.65±0.33 mm, 0.05 mm (range 0-0.30 mm) and 5.1° (range, 0-31.97°) at baseline to 1.98±0.43 mm ( P =0.073), 0.53 mm (range 0.42-0.91 mm, P =0.015), 45.9° (range, 40.2°-59.4°, ( P =0.015) in the long-term follow-up, respectively. The deepening of ACD and reopening of anterior chamber angle (ACA) was observed in 6 eyes (85.7%)., Conclusion: LCP is a promising treatment option for patients with CACG via reducing IOP and glaucoma medication without serious complications. In addition, LCP can bring a significant deepening in ACD and reopening of ACA., (International Journal of Ophthalmology Press.)

The bark of Streblus indicus , a Dai medicine in China, has been listed in the Chinese Materia Medica as possessing hemostatic and analgesic properties. Ethnic medicine books record that its bark or leaves for the treatment of mumps and lymphoma. However, according to the literature survey, anti-inflammatory and analgesic studies available for leaves and branches of S. indicus have been seldom reported so far. The current study focuses on the metabolites of S. indicus bark and leaves responsible for anti-inflammatory and analgesic effects on the basis of bioactive-included acetic acid writhing, hot-plate, and xylene-induced ear swelling. The secretion of inflammatory mediators, TNF- α , IL-6, IL-1 β , IL-4, and IL-10, were evaluated for their anti-inflammatory by xylene-induced in mouse ear cells. Histological examination was used to assess the anti-inflammatory and analgesic effects of the branches and leaves of S. indicus , and Western blot analysis determined the mechanism of the methanolic extract of branches and leaves. Different metabolites of S. indicus significantly alleviated analgesic and anti-inflammatory effects, with no discernable differences among them. All metabolites decreased the levels of TNF- α , IL-1 β , and IL-6 and increased the levels of IL-4 and IL-10. The analgesic and anti-inflammatory mechanism of the methanolic extract was related to the NF- k B signaling pathway. These results not only would account for scientific knowledge for the traditional application of S. indicus , but also provide a credible theoretical foundation for the further development of anti-inflammatory and analgesic agents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xie, Huang, Chen, Zhou, Zhou, Yang, Xu, Tan and Liu.)

Colletotrichum species are plant pathogens, saprobes and endophytes on various plant hosts. It is regarded as one of the 10 most important genera of plant pathogens in the world. Walnut anthracnose is one of the most severe diseases affecting walnut productivity and quality in China. In this study, 162 isolates were obtained from 30 fruits and 65 leaf samples of walnut collected in Beijing, China. Based on morphological characteristics and DNA sequence analyses of the concatenated loci, namely internal transcribed spacer (ITS), glyceraldehyde-3-phosphate dehydrogenase ( GAPDH ), actin ( ACT ), chitin synthase 1 ( CHS-1 ) and beta-tubulin (TUB2), these isolates were identified as two novel species of Colletotrichum , i.e. C.juglandicola and C.peakense . Koch's postulates indicated that both C.juglandicola and C.peakense could cause anthracnose in walnut., Competing Interests: The authors have declared that no competing interests exist., (Lin Zhang, Yue-Qi Yin, Li-Li Zhao, Yu-Qing Xie, Jing Han, Ying Zhang.)

Microbial degradation has been confirmed as effective and environmentally friendly approach to remediate phthalates from the environment, and hydrolase is an effective element for contaminant degradation. In the present study, a novel dibutyl phthalate (DBP)-hydrolyzing carboxylesterase (named PS06828) from Pseudomonas sp. PS1 was heterogeneously expressed in E. coli, which was identified as a new member of the lipolytic family VI. Purified PS06828 could efficiently degrade DBP with a wide range of temperature (25-37 °C) and pH (6.5-9.0). Multi-spectroscopy methods combined with molecular docking were employed to study the interaction of PS06828 with DBP. Fluorescence and UV-visible absorption spectra revealed the simultaneous presence of static and dynamic component in the fluorescence quenching of PS06828 by DBP. Synchronous fluorescence and circular dichroism spectra showed inconspicuous alteration in micro-environmental polarity around amino acid residues but obvious increasing of α-helix and reducing of β-sheet and random coil in protein conformation. Based on the information on exact binding sites of DBP on PS06828 provided by molecular docking, the catalytic mechanism mediated by key residues (Ser113, Asp166, and His197) was proposed and subsequently confirmed by site-directed mutagenesis. The results can strengthen our mechanistic understanding of family VI esterase involved in hydrolysis of phthalic acid esters, and provide a solid foundation for further enzymatic modification., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses challenges to the effectiveness of neutralizing antibodies. Rational design of antibody cocktails is a realizable approach addressing viral immune evasion. However, evaluating the breadth of antibody cocktails is essential for understanding the development potential. Here, based on a replication competent vesicular stomatitis virus model that incorporates the spike of SARS-CoV-2 (VSV-SARS-CoV-2), we evaluated the breadth of a number of antibody cocktails consisting of monoclonal antibodies and bispecific antibodies by long-term passaging the virus in the presence of the cocktails. Results from over two-month passaging of the virus showed that 9E12 + 10D4 + 2G1 and 7B9-9D11 + 2G1 from these cocktails were highly resistant to random mutation, and there was no breakthrough after 30 rounds of passaging. As a control, antibody REGN10933 was broken through in the third passage. Next generation sequencing was performed and several critical mutations related to viral evasion were identified. These mutations caused a decrease in neutralization efficiency, but the reduced replication rate and ACE2 susceptibility of the mutant virus suggested that they might not have the potential to become epidemic strains. The 9E12 + 10D4 + 2G1 and 7B9-9D11 + 2G1 cocktails that picked from the VSV-SARS-CoV-2 system efficiently neutralized all current variants of concern and variants of interest including the most recent variants Delta and Omicron, as well as SARS-CoV-1. Our results highlight the feasibility of using the VSV-SARS-CoV-2 system to develop SARS-CoV-2 antibody cocktails and provide a reference for the clinical selection of therapeutic strategies to address the mutational escape of SARS-CoV-2., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objective: To investigate the efficacy and safety of transcatheter aortic valve replacement (TAVR) in the treatment of severe aortic stenosis. Methods: The clinical data of patients with severe aortic stenosis who underwent TAVR at the People's Hospital of Xinjiang Uygur Autonomous Region between September 2016 and September 2022 were retrospectively analyzed. Changes in aortic transvalvular pressure gradients, valve orifice area, and activity tolerance of patients before and after the surgery were compared. Moreover, postoperative complications and follow-up results from 30 days to 6 years after the surgery were recorded. Results: A total of 76 patients were included in the study (50 males and 26 females), with an average age of (71.3±7.6) years, including 16 rheumatic valvular diseases, 60 senile degenerative diseases, 46 bicuspid valves and 30 tricuspid valves. The success rate of the operation was 96.1% (73/76). Compared with that before the operation, the mean aortic transvalvular pressure gradients decreased [(8.5±2.8) mmHg vs (68.5±19.2) mmHg (1 mmHg=0.133 kPa), P <0.001], but the valve orifice area increased [(1.91±0.31) cm 2 vs (0.65±0.21) cm 2 , P <0.001]. Likewise, six-minute walking test (6MWT) showed that walking distance was longer after the surgery [(430±13) m vs (201±28) m, P <0.001]. There were 1 case of retroperitoneal hematoma, 1 case of stricture balloon dilatation after femoral artery suture concomitant with postoperative puncture site infection, 1 case of femoral artery surgical incision, 2 cases of valve-in-valve (ViV) and 5 cases of perivalvular leakage (4 cases were mild and 1 case was moderate) after the surgery, respectively. Moreover, acute left main artery occlusion during operation occurred in 1 case, ventricular rupture during operation occurred in 1 case and the patient was transferred to valve replacement surgery and finally dead, delayed coronary artery occlusion and death happened in 1 case, and all of the above-mentioned 3 cases were due to surgical failure. Postoperative pacemaker implantation due to third-degree atrioventricular block was performed in 5 cases. There were 1 case of pulmonary embolism, 1 case of transient right limb disorder, 1 case of gastrointestinal bleeding and 1 case of urethral bleeding after the surgery, respectively. The patients were followed up for (1.0±0.1) years (30 days to 6 years), and the results showed that 2 cases died, including 1 case died suddenly at home (the cause of death was unknown) and 1 case died of acute heart failure 8 months after the surgery. Chronic heart failure occurred repeatedly in 6 cases. The quality of life of other patients improved significantly. Conclusion: TAVR is effective and safe for patients with severe aortic stenosis.

Aim: To evaluate the trend of glaucoma internal filtration surgeries for inpatients between 2015 and 2021 at the Eye Hospital of Wenzhou Medical University., Methods: A review of the medical records of inpatients who had been diagnosed with glaucoma and received anti-glaucoma surgery between January 1, 2015 and December 31, 2021 was conducted. The glaucoma diagnosis in this study included primary open angle glaucoma, primary angle-closure glaucoma, secondary glaucoma, and paediatric glaucoma. The types of surgeries were categorised as internal filtration, external filtration, and cyclodestruction surgery based on the pathway of aqueous humor outflow. The trend of these glaucoma surgeries in the sample of patients with different types of glaucoma was then analysed., Results: The number of patients hospitalised for glaucoma surgery increased yearly, from 752 in 2015 to 1373 in 2021, at the Eye Hospital of Wenzhou Medical University. Regarding the patients diagnosed with primary open angle glaucoma, internal filtration surgery increased from 27.40% of the sample to 54.40% of the sample, while external filtration surgery decreased from 71.50% to 44.20% between 2015 and 2021. For paediatric glaucoma, internal filtration surgery increased from 37.50% in 2015 to 88.20% in 2021. Whilst different types of surgeries were performed on the sample of patients with secondary glaucoma, the proportion of internal filtration surgery also showed an increase from 18.20% in 2015 to 40.90% in 2021. Meanwhile, internal filtration surgery in the patient sample with primary angle-closure glaucoma already accounted for over 70.00% in 2015, and showed a small increase by 2021., Conclusion: As surgical technology and surgical experience continue to elevate and improve, the range of glaucoma surgeries are correspondingly evolving. This study find that internal filtration surgeries accounted for an increasing proportion of treatments in the surgical management of glaucoma between 2015 and 2021., (International Journal of Ophthalmology Press.)

Objective: The aim of this study was to examine serum leukocyte cell-derived chemotaxin 2 (LECT2) levels in osteoporosis subjects to confirm its association with osteoporosis., Methods: A total of 204 adult subjects were recruited. Bone mineral densities (BMD) were assessed and blood samples were collected for measurements of biomedical parameters and the bone turnover markers. Serum LECT2 levels were measured by enzyme-linked immunosorbent assay. The relationships between serum LECT2 levels and other parameters were analyzed using the Spearman correlation coefficient., Results: Serum LECT2 levels were significantly increased in osteoporosis subjects over controls. We found a significantly negative correlation of serum LECT2 with BMD, 25-hydroxy-vitamin D, and creatinine and a significantly positive correlation with C-terminal telopeptide of type 1 collagen and total cholesterol., Conclusion: Serum LECT2 levels were significantly upregulated in osteoporosis subjects and correlated with the severity of bone loss. Serum LECT2 could be a potential biomarker to assess the risk of bone loss., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

HIV infection has been reported to cause bone loss and a higher risk of fracture. Under normal conditions, bone metabolism is regulated by mesenchymal cells, osteoclasts differentiated from mononuclear macrophages, osteoblasts, and their expression of regulatory factors, such as receptor activator of nuclear factor-kappa B ligand (RANKL), M-SCF, and transforming growth factor-beta. The balance between bone resorption and osteogenesis depends on the balance between osteoclasts and osteoblasts. In addition, some immune cells, such as B-cells, T-cells, and other non-immune cells expressing RANKL, can contribute to osteoporosis under inflammatory conditions. HIV proteins consist of three types: regulatory proteins, accessory proteins, and structural proteins, which contribute to HIV-mediated bone loss partly by upregulating NF-κB expression, tumor necrosis factor alpha content, and release of inflammatory cytokines. Even worse, although antiretroviral therapy has reduced HIV infection mortality and successfully transformed acquired immunodeficiency syndrome into a chronic disease, its impact on bone loss should not be overlooked, especially when the drug contains tenofovir. This review analyzes some reports focusing on the overall osteolytic situation due to imbalances in osteogenesis and bone resorption due to HIV infection and antiviral therapy. The intrinsic mechanism of bone loss provides a reference for researchers to analyze the risk factors for HIV patients complicated with bone loss and helps clinicians to provide ideas for the intervention and prevention of bone loss during clinical treatment and chronic disease management of HIV patients., (Copyright: © 2023 Permanyer.)

A copper-mediated trifluoromethyltelluration of arylboronic acids with [Me 4 N][TeCF 3 ] using air as an environmental friendly oxidant is presented. The reaction proceeded smoothly under mild conditions in the presence of Cu(OTf) 2 and bipyridine to provide the corresponding trifluoromethyltellurated products in good yields. Vinylboronic acid and arylboronic acid pinacol ester were also suitable substrates in the conversion but the yields are low. This transformation featured simplicity, good functional group tolerance, and a wide range of substrates, allowing for a convenient access to various TeCF 3 -containing molecules, and represented the first Chan-Lam type trifluoromethyltelluration with the highly reactive [Me 4 N][TeCF 3 ] salt., Competing Interests: The authors declare no competing interest., (© 2022 The Author(s).)

Studies have investigated associations between maternal exposure to PFAS and preterm birth, but the impact of paternal and overall family exposure to PFAS mixtures on preterm birth remains unknown. To address this knowledge gap, a total of 355 preterm births and 481 controls were selected for a family-based birth cohort study in a coastal area of China, between 2016 and 2018. Seven PFAS, including perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA), were quantified in maternal, paternal and neonatal sera. Preterm birth was defined as live delivery at <37 completed gestational weeks. Bayesian kernel machine regression (BKMR) model was used to inspect the combined effect of family PFAS mixtures. Latent class analysis was used to identify family-level PFAS exposure profiles. Multiple linear regression analysis showed higher odds of preterm birth in association with higher maternal PFBA (OR = 1.16, 95%CI:1.09, 1.25), PFOA (OR = 1.51, 95%CI:1.27, 1.80), PFOS (OR = 2.07, 95%CI:1.70, 2.52) and PFNA (OR = 1.36, 95%CI: 1.01, 1.83), and neonatal PFBA (OR = 1.16, 95%CI:1.05,1.29), PFHxA (OR = 1.46, 95%CI:1.32, 1.62), PFHxS (OR = 1.15, 95%CI:1.05, 1.26) and PFNA (OR = 1.30, 95%CI:1.09,1.56). The associations were reversed between individual paternal PFAS exposures and preterm birth. At the family level, higher PFAS mixture concentration was associated with higher odds of preterm birth. In particular, higher PFNA and PFDA exposure was associated with greater preterm birth risk (OR = 2.55, 95%CI:1.45, 4.50). The PFAS-preterm association was modified by family-level seafood consumption. Our results suggest that higher family-level PFNA and PFDA exposure was associated with greater preterm birth risk, although the results for individual paternal, maternal and neonatal PFAS exposures were contradictory. If replicated in other coastal areas, these findings highlight a need to focus on the family triad and to consider seafood consumption when assessing the reproductive toxicity of PFAS exposure., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Rheumatoid arthritis (RA) is a common autoimmune disease. Paederia scandens (Lour.) Merr is a common folk remedy used in Hainan, China, to dispel the wind and dampness associated with RA., Methods: The active components of Paederia scandens were extracted using network pharmacology. The potential targets of active components were used to determine activated pathways, and the in vitro effects of Paederia scandens extracts were verified in RA fibroblast-like synoviocytes (HFLS-RA)., Results: We identified 27 active components using ultra-high-performance liquid chromatography (UHPLC)-quadrupole time-of-flight (QTOF)-mass spectrometry (MS). Among the major target genes with high connectivity, IL-1β, PI3K, TNF, and JAK2 are known to play key roles in RA development. High-affinity interactions were identified between active compounds in Paederia scandens extract and Janus kinase JAK 2, which are key components of the JAK-signal transducer and activator of transcription (STAT) signaling pathway. In HFLS-RA cells, Paederia scandens extract treatment reduced the mRNA levels of IL-6, IL-1β, and IL-17 . Paederia scandens extract treatment also significantly inhibited the phosphorylation of JAK 2 and STAT3, regulating cell proliferation., Conclusions: Based on these results, we confirmed that Paederia scandens has potential for application as a therapeutic and preventive food and acts through the modulation and suppression of JAK-STAT pathway activation to control the inflammatory response in RA., Competing Interests: None., (AJTR Copyright © 2022.)

Aim: To report the outcomes of penetrating canaloplasty for corticosteroid-induced glaucoma in a case series., Methods: Penetrating canaloplasty is a bleb-independent filtering surgery unifying canaloplasty and trabeculectomy. In this study, the surgery was performed to restore the natural outflow through surgically expanded Schlemm's canal and generated trabeculum ostium. A total of 10 eyes of 8 patients were treated with penetrating canaloplasty for corticosteroid-induced glaucoma. Intraocular pressure (IOP) and the number of glaucoma medications at postoperative 3, 6, 12, 18, 24, 36, and 48mo were documented as primary endpoint. Complications after the surgery were recorded as secondary endpoint., Results: Penetrating canaloplasty was accomplished successfully for all 10 eyes, with a mean follow-up of 20.4±13.0mo (range 6-48mo). The mean preoperative IOP and number of anti-glaucoma medications were 45.1±6.5 mm Hg and 3.3±0.5 respectively. The mean post-operative IOP at 3, 6, 12, 18, 24, 36, and 48mo were 15.8±6.0, 14.7±3.3, 15.3±2.0, 15.6±2.6, 17.5±1.8, 16.5±4.9, and 14.0 mm Hg. The number of anti-glaucoma medications at these time points were all 0. This surgery failed to control the IOP in 1 eye at 1mo after surgery. Hyphaema occurred in 3 eyes on the first day after surgery. Postoperative transient IOP increasing was encountered with in two eyes from 1wk to 1mo after surgery. Choroidal detachment developed in one eye but responded well to conservative treatment., Conclusion: Penetrating canaloplasty is effective for corticosteroid-induced glaucoma without serious complications, making it a viable or preferred alternative option., (International Journal of Ophthalmology Press.)

Traditional Chinese Medicine is generally used as a decoction to guard health. Many active ingredients in the decoction are chemical ingredients that are not usually paid attention to in phytochemical research, such as polysaccharides, etc. Based on research interest in Chinese herbal decoction, crude polysaccharides from G. wilfordii (GCP) were purified to obtain two relatively homogeneous polysaccharides, a neutral polysaccharide (GNP), and an acid polysaccharide (GAP) by various chromatographic separation methods, which were initially characterized by GC-MS, NMR, IR, and methylation analysis. Studies on the hepatoprotective activity of GCP in vivo showed that GCP might be a potential agent for the prevention and treatment of acute liver injury by inhibiting the secretion levels of ALT, AST, IL-6, IL-1 β , TNF- α , and MDA expression levels, increasing SOD, and the GSH-Px activity value. Further, in vitro assays, GNP and GAP, decrease the inflammatory response by inhibiting the secretion of IL-6 and TNF- α , involved in the STAT1/T-bet signaling pathway.

Aim: To investigate fluctuation of intraocular pressure (IOP) and seasonal variation of 24-hour IOP during one year in healthy participants., Methods: Totally 13 young healthy volunteers participated in this study. IOP was measured with Canon TX-20 at about 8:00-9:00 a.m . from Monday to Friday every week for a whole year. They also underwent 24-hour IOP examination every three months. Blood pressure, heart rate, temperature, humidity, atmosphere pressure, sunshine duration and other environment parameters were recorded., Results: The yearly fluctuation curve showed IOP in the summer months were lower than other seasons. In the multivariable generalized estimating equation analysis, IOP had a negative correlation with both temperature and sunshine duration ( P <0.05). There also was a seasonal effect on 24-hour IOP. However, all intraclass correlation coefficients values of minimum, maximum and average of the 24-hour IOP and each individual IOP were less than 0.30., Conclusion: IOP is trend to be higher in cold days than warm days. IOP have negative association with both environmental temperature and duration of sunshine. On a season-to-season basis, 24-hour IOP is not highly reproducible in healthy volunteers., (International Journal of Ophthalmology Press.)

Background: Balloon-expandable valves (BEV) and self-expanding valves (SEV) for transcatheter aortic valve replacement (TAVR) have shown promising results in Western populations. Herein, we comparatively evaluated their hemodynamics and early clinical outcomes in a Chinese population., Methods: One hundred seventy-eight patients with symptomatic aortic stenosis who had undergone transfemoral TAVR using SEV (n=153; Venus-A, 97; VitaFlow, 56) or BEV (n=25; Sapien3) from September 2020 to April 2021 were retrospectively enrolled, and 25 pairs were propensity-score matched for 10 baseline variables. The primary study outcomes were aortic valve hemodynamics and postoperative complications at discharge and 3-month follow-up., Results: TAVR was successful in all patients. Compared with SEV group, the BEV group had similarly distributed baseline characteristics, procedural time, hospital stay, new pacemaker implantation, and paravalvular regurgitation grade. We also observed that the BEV group had lower rates of balloon pre-dilation (60% vs. 92%, P=0.018), post-dilation (0 vs. 20%, P=0.050) and second valve implantation (0 vs. 24%, P=0.022); higher mean transaortic gradient (14.3±6.1 vs. 10.8±4.9, P=0.030) and proportion of patients with elevated gradients (20% vs. 0, P=0.050) at discharge; and similar rehospitalization, mean transaortic gradient, new pacemaker implantation, and paravalvular regurgitation grade than the SEV group at the 3-month follow-up. There were no deaths in either group. However, the proportion of patients with elevated gradients in SEV group was higher at 3 months than before discharge (24% vs. 0, P=0.022)., Conclusions: BEV and SEV for transfemoral TAVR appear comparably safe and effective, with high device success and favorable 3-month clinical outcomes. However, the transaortic gradient and new pacemaker implantation in the SEV group increased during follow-up, warranting larger studies with longer-term follow-up., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-21-6637/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Immune stimulatory antibodies and cytokines elicit potent antitumor immunity. However, the dose-limiting systemic toxicity greatly hinders their clinical applications. Here, we demonstrate a chemical approach, termed “switchable” immune modulator (Sw-IM), to limit the systemic exposure and therefore ameliorate their toxicities. Sw-IM is a biomacromolecular therapeutic reversibly masked by biocompatible polymers through chemical linkers that are responsive to tumor-specific stimuli, such as high reducing potential and acidic pH. Sw-IMs stay inert (switch off) in the circulation and healthy tissues but get reactivated (switch on) selectively in tumor via responsive removal of the polymer masks, thus focusing the immune boosting activities in the tumor microenvironment. Sw-IMs applied to anti–4-1BB agonistic antibody and IL-15 cytokine led to equivalent antitumor efficacy to the parental IMs with markedly reduced toxicities. Sw-IM provides a highly modular and generic approach to improve the therapeutic window and clinical applicability of potent IMs in mono- and combinational immunotherapies.

Background: Exposure to perfluoroalkyl acids (PFAAs) is known to be associated with metabolic disorders. However, whether PFAAs isomers are associated with metabolic syndrome (MetS) still remains unknown., Objectives: To explore the associations between serum PFAAs isomers and MetS., Methods: We recruited 1,501 adults from a cross-sectional study, the "Isomers of C8 Health Project in China" to investigate the associations between PFAAs isomers and MetS. A total of 20 PFAAs including the isomers of PFOS and PFOA were detected. Logistic regression models and restricted cubic spline models were used to evaluate the relationship of serum PFAAs isomers exposure with MetS and its components as well after adjusting for covariates., Results: The MetS prevalence in our study was 43.0%. The serum levels of both PFOS and PFOA isomers were higher in participants with MetS than that with non-MetS (p < 0.05). We found positive associations for per natural log-transformed ng/mL of branched perfluorooctane sulfonate (br-PFOS) (odds ratio (OR) = 1.18, 95% confidence interval (CI): 1.01, 1.38)) linear perfluoronanoic acid (n-PFOA) (OR = 1.35, 95% CI: 1.16, 1.58) and perfluoro-6-methylpheptanoic acid (6 m-PFOA) (OR = 1.32, 95% CI: 1.11, 1.57) with higher odds of MetS after covariates adjustment, while null association was observed for linear isomers of PFOS (OR = 1.09, 95% CI: 0.94, 1.25). We found a nonlinear dose-response relationship with a "threshold" effect in serum br-PFOS isomers with MetS, in which the odds of MetS increased quickly with increasing serum br-PFOS isomers under low exposure (p for nonlinearity = 0.030)., Conclusion: We report new evidence of associations between PFAAs isomers and MetS and the nonlinearity of dose-response relationship with br-PFOS isomers. Our findings indicate that more attention is needed to pay on the nonlinearity of dose-response relationship when investigate the association of PFAAs isomers with human health., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To study the value of fecal calprotectin (FC) in the diagnosis of neonatal necrotizing enterocolitis (NEC) through a Meta analysis., Methods: Web of Science, Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, Weipu Periodical Database, Wanfang Data, Chinese Biomedical Literature Database were searched for related studies published up to May 2020, with manual search as supplementation. The QUADAS criteria were used to evaluate the quality of the articles included. Meta-DiSc 1.4 and Stata 15.0 software were used to perform the Meta analysis, including the evaluation of specificity, sensitivity, likelihood ratio, and diagnostic odds ratio. The sensitivity analysis and heterogeneity testing were performed, and the summary receiver operating characteristic (SROC) curve and Fagan diagram were plotted., Results: A total of 15 articles were enrolled, involving 1 719 neonates. Among these articles, 4 had low quality, 2 had high quality, and the rest had medium quality. There was high heterogeneity between studies, and there was no threshold effect or publication bias. The random effects model analysis showed that FC had a pooled specificity of 0.80 (95% CI :0.78-0.82) and a sensitivity of 0.86 (95% CI :0.83-0.89) in the diagnosis of NEC, with a negative likelihood ratio of 0.19 (95% CI :0.14-0.26), a positive likelihood ratio of 4.71 (95% CI :3.57-6.23), and a diagnostic odds ratio of 29.56 (95% CI :17.98-48.61). The area under the SROC curve was 0.9131 and the Q * index was 0.8456. The Fagan diagram showed that the post-test probability of NEC indicated by negative FC was 13%, while that indicated by positive FC was 86%. The Meta regression analysis showed that the heterogeneity came from other non-threshold factors., Conclusions: FC has high potential and efficiency in the early diagnosis of NEC. FC measurement can be used for the diagnosis of NEC, but it should be combined with clinical manifestations and other related laboratory examinations.

Background: Trimethylamine- N -Oxide (TMAO) is a proatherogenic and prothrombotic metabolite. Our study examined the association of plasma TMAO level with cardiovascular and all-cause mortality in hemodialysis (HD) patients., Methods: Patients who were at least 18 years-old and received HD for at least 6 months were enrolled within 6 months. Patients with coronary heart disease, congestive heart failure, arrhythmia, or stroke within 3 months before study onset were excluded. The primary endpoints were cardiovascular and all-cause death, and the secondary endpoint was cerebrovascular death., Results: We recruited 252 patients and divided them into a high-TMAO group (>4.73 μg/mL) and a low-TMAO group (≤4.73 μg/mL). The median follow-up time was 73.4 months (interquartile range: 42.9, 108). A total of 123 patients died, 39 from cardiovascular disease, 19 from cerebrovascular disease, and 65 from other causes. Kaplan-Meier analysis indicated that the high-TMAO group had a greater incidence of cardiovascular death (Log-Rank: p  = 0.006) and all-cause death (Log-Rank: p  < 0.001). Cox regression analysis showed that high TMAO level was significantly associated with cardiovascular and all-cause mortality. After adjustment for confounding, this association remained significant for cardiovascular mortality (TMAO as a continuous variable: HR: 1.18, 95%CI: 1.07, 1.294, p  < 0.001; TMAO as a dichotomous variable: HR: 3.44, 95%CI: 1.68, 7.08, p  < 0.001) and all-cause mortality (TMAO as a continuous variable: HR: 1.14, 95%CI: 1.08, 1.21, p  < 0.001; TMAO as a dichotomous variable: HR: 2.54, 95%CI: 1.71, 3.76, p  < 0.001)., Conclusions: High plasma TMAO level is significantly and independently associated with cardiovascular and all-cause mortality in HD patients.

Background: Percutaneous balloon pulmonary valvuloplasty (PBPV) is the procedure of choice for uncomplicated severe or symptomatic pulmonary stenosis. Echocardiography (echo)-guided PBPV can completely avoid the use of radiation and contrast agents compared to fluoroscopy-guided PBPV. Although we have confirmed that echo-guided PBPV is feasible in humans, the poor visibility of the traditional catheter under echo greatly limits the promotion of this new technology., Methods: We produced a novel double-balloon catheter to make the catheter easy to be detected by echo through adding a guiding balloon at the distal end of the catheter. Echo-guided PBPV was performed on thirty healthy swine using either a novel catheter or a traditional catheter to evaluate the feasibility and safety of the novel double-balloon catheter. The feasibility was evaluated by the success rate of balloon inflation at the pulmonary valve annulus and the operating time. The safety was evaluated by the frequency of balloon slippage and the incidence of complications., Results: There were no significant between-group differences in terms of weight and the ratio of balloon diameter to pulmonary annulus diameter. The success rate was 93.3% and 60% in the novel and traditional groups, respectively. The novel group had significantly (p<0.05) lower mean procedure time (6.33±6.86min vs 24.8±9.79min) and lower frequency of balloon slippage (0.07±0.26 vs 0.53±0.52), arrhythmia (0.07±0.26 vs 0.47±0.52), and tricuspid regurgitation (6.7% vs 40%) than the traditional group. No myocardial hematoma or pericardial tamponade occurred in the novel catheter group., Conclusion: Although further studies and improvements are required, the study results indicate that the novel double-balloon catheter for echo-guided PBPV is feasible and safe., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

In insect parasitoids, fatty acid synthases (FASs) have received less attention and their roles associated with lipogenesis loss are far from clear. Meteorus pulchricornis is a solitary endoparasitoid wasp of many larvae of lepidopteran pests. The lipid content during developmental stages of M. pulchricornis was measured; it was higher in the larval and pupal stages but declined from six-day-old pupae. Lipid accumulation constantly decreased in the adult stage, even after feeding on honey solutions. To investigate the roles of FASs in lipid synthesis in M. pulchricornis , four FAS genes ( MpulFAS1~4 ) were identified from the transcriptome database of M. pulchricornis . All FAS genes included full-length open reading frames and shared 72-79% similarity with the sequences of Microplitis demolitor . qRT-PCR validation showed that all four FASs had the highest expression after the adult wasps were fed on honey diets. MpulFAS1 and MpulFAS2 reached their expression peaks at the adult stage but MpulFAS3 and MpulFAS4 peaked at the larval stage. To further study the function of FASs, dsRNA injection knocked down the expression of four MpulFASs and resulted in a significant decline of lipid content at the adult stage in M. pulchricornis . Results from this study suggest that M. pulchricornis adults cannot accumulate lipid content effectively and FASs may still contribute to lipid synthesis in the adult stage. This broadens the knowledge on the ability of lipid synthesis in parasitoid wasps and provides insight into the roles of FASs in insects with parasitic life-history traits.

An efficient strategy for the construction of fused imidazole derivatives through a palladium-catalyzed isocyanide insertion reaction has been accomplished. The methodology provides an operationally simple and versatile route for the synthesis of indeno[1,2- d ]imidazole and imidazo[1,2- a ]indole skeletons which are rarely reported. The key features of the protocol are construction of sequential C-C/C-C/C-N bonds via C(sp 2 )-H functionalization of imidazole at the C2- and C4-position, respectively. The compounds can be synthesized with diverse scaffolds, easily accessible starting materials, and moderate to good yields.

To investigate associations between central visual function and inner retinal structure in primary open-angle glaucoma (POAG). This study enrolled 78 POAG patients and 58 healthy controls. POAG was classified into early glaucoma and moderate to advanced glaucoma. The following tests were performed on all participants: isolated-check visual evoked potential (icVEP) testing, 24-2 standard automated perimetry (SAP), and Cirrus optical coherence tomography (OCT) examinations. Signal-to-noise ratio (SNR) measures obtained from icVEP responses to isolated checks presented at four depths of modulation (DOMs; 8%, 14%, 22%, and 32%) were explored. Mean macular sensitivity (mMS) was assessed by calculating the mean sensitivities of central 12 SAP points. Ganglion cell layer+ inner plexiform layer thickness (GCL+IPLT) and peripapillary retinal nerve fiber layer thickness (pRNFLT) were measured by OCT scanning. For each group of subjects, linear relationships among the following measures were analyzed: SNR, mMS, GCL+IPLT, and pRNFLT. SNR, mMS, GCL+IPLT, and pRNFLT were all more significantly decreased in glaucoma than in controls (P<0.001). A significant positive association was found between SNR at 14% DOM and GCL+IPLT at the inferior sector in early glaucoma (r=0.465, P=0.004). In moderate to advanced glaucoma, significant correlations were found between SNR at 32% DOM and mean GCL+IPLT (r=0.364, P=0.023), superior GCL+IPLT (r=0.358, P=0.025), and mean pRNFLT (r=0.396, P=0.025). In addition, in moderate to advanced glaucoma, there were significant correlations between mMS and all relevant measures of retinal thickness (r=0.330-0.663, P< 0.010). In early glaucoma, significant correlations were found between mean mMS and minimum GCL+IPLT (r=0.373, P=0.023), and between inferior mMS and superior GCL+IPLT (r=0.470, P=0.003). Linear models provided a good explanation for the relationship between SNR and inner retinal thickness (IRT), whereas nonlinear models better explained the relationship between mMS and IRT. In early glaucoma, both SNR and mMS were related moderately and significantly to IRT, whereas in moderate to advanced glaucoma, mMS was more strongly correlated with IRT than SNR.

Accumulating evidence has demonstrated that long noncoding RNAs (lncRNAs) exert essential biological functions in modulating the progression of endometrial carcinoma (EC). HOX transcript antisense intergenetic RNA (HOTAIR) has been widely recognized as a crucial mediator in various tumors, including EC. However, the specific molecular mechanism of HOTAIR in the development of EC remains to be further explored. In the present study, we demonstrated that HOTAIR was significantly upregulated in EC tissues; this was negatively correlated with PTEN but positively correlated with phosphatidylinositol 3-kinase (PI3K) and Akt. Overexpression of HOTAIR promoted proliferation and inhibited apoptosis of EC cells, similar to PTEN knockdown. Additionally, RNA pulldown demonstrated the direct binding relationship between HOTAIR and PTEN. Furthermore, HOTAIR activated the PI3K/Akt pathway to promote EC progression by suppressing PTEN in vivo Taking these results together, we revealed that high expression of HOTAIR promoted cell proliferation and inhibited apoptosis through activating the PI3K/Akt pathway via binding to PTEN, which might provide a prognostic marker and therapeutic target of EC., (Copyright © 2019 American Society for Microbiology.)

Objective: To study the clinical efficacy of interactive group sandplay versus individual sandplay in the treatment of preschool children with autism spectrum disorder (ASD)., Methods: A total of 80 ASD children, aged 4-6 years, were enrolled and randomly divided into experimental and control groups, with 40 children in each group. The children in the experimental group joined group sandplay with normal children at a ratio of 1: 3, and those in the control group were treated with individual sandplay. The Aberrant Behavior Checklist (ABC) and Autism Treatment Evaluation Checklist (ATEC) were used to evaluate the treatment outcome after three months of intervention., Results: There were 33 children in the experimental group and 28 in the control group. After three months of intervention, the experimental group had significant reductions in the scores of irritability, social withdrawal, and stereotypic behavior and the total score of the ABC scale (P<0.05), and the control group had significant reductions in the scores of behavior and inappropriate speech and the total score of the ABC scale (P<0.05). Compared with the control group, the experimental group had significantly greater improvements in the score of social withdrawal and the total score of the ABC scale after three months of intervention (P<0.05). After three months of intervention, the experimental group had significant reductions in the scores of sociability, sensory and cognitive awareness, and physical/health behavior and the total score of the ATEC scale (P<0.05), and the control group had significant reductions in the scores of speech, sociability, and physical/health behavior and the total score of the ATEC scale (P<0.05). Compared with the control group, the experimental group had significantly greater improvements in the scores of speech, sociability, and sensory and cognitive awareness and the total score of the ATEC scale after intervention (P<0.01). Compared with the control group, the experimental group also had significantly greater improvements in eye contact and sand stereotyped arrangement (P<0.05)., Conclusions: Both interactive group sandplay and individual sandplay are effective in the treatment of ASD in preschool children. Interactive group sandplay is better than individual sandplay in the treatment of ASD, with significant improvements in sociability, emotion and stereotypic behavior.

Objective: To study the clinical effect of psychological and behavioral intervention combined with biofeedback in the treatment of preschool children with attention deficit hyperactivity disorder (ADHD)., Methods: Sixty children each with inattentive, hyperactive/impulsive or combined type ADHD were enrolled. According to the intervention measure, they were randomly divided into 4 groups: control, psychological and behavioral intervention, biofeedback treatment and comprehensive treatment (psychological and behavioral intervention + biofeedback). Attention concentration time and impulse/hyperactivity and hyperactivity index scores of the Conners Parent Symptom Questionnaire (PSQ) were evaluated after 4 months of treatment., Results: The attention concentration time increased in all types children with ADHD after psychological and behavioral intervention, biofeedback treatment or comprehensive treatment (P<0.05). In children with inattentive ADHD, hyperactive/impulsive ADHD or combined-type ADHD, biofeedback or comprehensive treatment reduced the impulse/hyperactivity index score (P<0.05). In children with inattentive or combined-type ADHD, psychological and behavioral intervention or comprehensive treatment reduced the hyperactivity index score (P<0.05). In children with hyperactive/impulsive ADHD, biofeedback treatment, psychological and behavioral intervention or comprehensive treatment reduced the hyperactivity index score (P<0.05)., Conclusions: In children with ADHD, psychological and behavioral intervention combined with biofeedback treatment can improve the attention concentration and impulsive/hyperactive and hyperactive symptoms. The treatment strategies are slightly different for children with different types of ADHD.

The genome of kiwifruit (Actinidia chinensis) was sequenced previously, the first in the Actinidiaceae family. It was shown to have been affected by polyploidization events, the nature of which has been elusive. Here, we performed a reanalysis of the genome and found clear evidence of 2 tetraploidization events, with one occurring ∼50-57 million years ago (Mya) and the other ∼18-20 Mya. Two subgenomes produced by each event have been under balanced fractionation. Moreover, genes were revealed to express in a balanced way between duplicated copies of chromosomes. Besides, lowered evolutionary rates of kiwifruit genes were observed. These findings could be explained by the likely auto-tetraploidization nature of the polyploidization events. Besides, we found that polyploidy contributed to the expansion of key functional genes, e.g., vitamin C biosynthesis genes. The present work also provided an important comparative genomics resource in the Actinidiaceae and related families., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Adoptive cell therapy (ACT) with antigen-specific T cells has shown remarkable clinical success; however, approaches to safely and effectively augment T cell function, especially in solid tumors, remain of great interest. Here we describe a strategy to 'backpack' large quantities of supporting protein drugs on T cells by using protein nanogels (NGs) that selectively release these cargos in response to T cell receptor activation. We designed cell surface-conjugated NGs that responded to an increase in T cell surface reduction potential after antigen recognition and limited drug release to sites of antigen encounter, such as the tumor microenvironment. By using NGs that carried an interleukin-15 super-agonist complex, we demonstrated that, relative to systemic administration of free cytokines, NG delivery selectively expanded T cells 16-fold in tumors and allowed at least eightfold higher doses of cytokine to be administered without toxicity. The improved therapeutic window enabled substantially increased tumor clearance by mouse T cell and human chimeric antigen receptor (CAR)-T cell therapy in vivo.