Cichorium glandulosum Ameliorates HFD-Induced Obesity in Mice by Modulating Gut Microbiota and Bile Acids.

Obesity is an ongoing global health problem, and Cichorium glandulosum (CG, chicory) is traditionally used as a hepatoprotective and lipid-lowering drug. However, there is still a lack of research on the role of CG in the treatment of obesity. In the present study, we found that CG significantly delayed weight gain and positively affected glucolipid metabolism disorders, serum metabolism levels, and the degree of liver and kidney oxidative stress in high-fat diet (HFD) mice. Further examination of the effects of CG on intestinal microenvironmental dysregulation and its metabolites in HFD mice revealed that the CG ethanol extract high-dose group (CGH) did not have a significant regulatory effect on short-chain fatty acids. Still, CGH significantly decreased the levels of 12α-OH/non-12α-OH bile acids and also found significant upregulation of proteobacteria and downregulation of cyanobacteria at the phylum level. CG may have ameliorated obesity and metabolic abnormalities in mice by repairing gut microbiota dysbiosis and modulating bile acid biosynthesis.

Screening of α-Glucosidase Inhibitors in Cichorium glandulosum Boiss. et Huet Extracts and Study of Interaction Mechanisms.

Cichorium glandulosum Boiss. et Huet (CGB) extract has an α-glucosidase inhibitory effect (IC50 = 59.34 ± 0.07 µg/mL, positive control drug acarbose IC50 = 126.1 ± 0.02 µg/mL), but the precise enzyme inhibitors implicated in this process are not known. The screening of α-glucosidase inhibitors in CGB extracts was conducted by bioaffinity ultrafiltration, and six potential inhibitors (quercetin, lactucin, 3-O-methylquercetin, hyperoside, lactucopicrin, and isochlorogenic acid B) were screened as the precise inhibitors. The binding rate calculations and evaluation of enzyme inhibitory effects showed that lactucin and lactucopicrin exhibited the greatest inhibitory activities. Next, the inhibiting effects of the active components of CGB, lactucin and lactucopicrin, on α-glucosidase and their mechanisms were investigated through α-glucosidase activity assay, enzyme kinetics, multispectral analysis, and molecular docking simulation. The findings demonstrated that lactucin (IC50 = 52.76 ± 0.21 µM) and lactucopicrin (IC50 = 17.71 ± 0.64 µM) exhibited more inhibitory effects on α-glucosidase in comparison to acarbose (positive drug, IC50 = 195.2 ± 0.30 µM). Enzyme kinetic research revealed that lactucin inhibits α-glucosidase through a noncompetitive inhibition mechanism, while lactucopicrin inhibits it through a competitive inhibition mechanism. The fluorescence results suggested that lactucin and lactucopicrin effectively reduce the fluorescence of α-glucosidase by creating lactucin-α-glucosidase and lactucopicrin-α-glucosidase complexes through static quenching. Furthermore, the circular dichroism (CD) and Fourier transform infrared spectroscopy (FT-IR) analyses revealed that the interaction between lactucin or lactucopicrin and α-glucosidase resulted in a modification of the α-glucosidase's conformation. The findings from molecular docking and molecular dynamics simulations offer further confirmation that lactucopicrin has a robust binding affinity for certain residues located within the active cavity of α-glucosidase. Furthermore, it has a greater affinity for α-glucosidase compared to lactucin. The results validate the suppressive impact of lactucin and lactucopicrin on α-glucosidase and elucidate their underlying processes. Additionally, they serve as a foundation for the structural alteration of sesquiterpene derived from CGB, with the intention of using it for the management of diabetic mellitus.

The antidepressant effects of protein arginine methyltransferase 2 involve neuroinflammation.

Protein arginine methyltransferase (PRMT) 2 catalyzes the methylation of arginine residues in histones. Depression is associated with histone methylation; however, more comprehensive research is needed on how PRMT2 regulates depression. The present study aimed to investigate the effects and possible mechanism(s) of PRMT2 overexpression on depression-like behavior induced by chronic unpredictable mild stress (CUMS) in rats, and whether lentivirus-mediated PRMT2 overexpression in the hippocampus suppresses depression-like behavior. Furthermore, the PRMT2 inhibitor MS023 was administered to the animals to investigate whether the antidepressant effect of PRMT2 overexpression could be reversed. Behavioral experiments were performed to detect depression-like behavior in rats. Western blotting was used to determine protein expression levels of PRMT2, histone H3R8 asymmetric dimethylation (H3R8me2a), inducible nitric oxide synthase (iNOS), and arginase 1 (Arg1) in rat hippocampal tissues. Hippocampal microglia and PRMT2 were stained using immunofluorescence techniques. Enzyme-linked immunosorbent assay was used to determine the levels of various inflammatory factors in rat hippocampal tissue. Results of analysis revealed that PRMT2 overexpression in the hippocampus exerted an antidepressant effect. PRMT2 overexpression in the hippocampus reduced the proportion of activated microglia in the hippocampus, upregulated Arg1 and H3R8me2a expression, and downregulated iNOS expression. PRMT2 overexpression in the hippocampus inhibited the release of pro-inflammatory factors and promoted the release of anti-inflammatory factors. In summary, PRMT2 overexpression in the hippocampus promoted the conversion of microglia from the M1 to M2 type, resulting in an antidepressant effect. These results suggest that PRMT2 may be a potential therapeutic target to prevent and treat depression.

Rational Lithium Salt Molecule Tuning for Fast Charging/Discharging Lithium Metal Battery.

The electrolytes for lithium metal batteries (LMBs) are plagued by a low Li+ transference number (T+) of conventional lithium salts and inability to form a stable solid electrolyte interphase (SEI). Here, we synthesized a self-folded lithium salt, lithium 2-[2-(2-methoxy ethoxy)ethoxy]ethanesulfonyl(trifluoromethanesulfonyl) imide (LiETFSI), and comparatively studied with its structure analogue, lithium 1,1,1-trifluoro-N-[2-[2-(2-methoxyethoxy)ethoxy)]ethyl]methanesulfonamide (LiFEA). The special anion chemistry imparts the following new characteristics: i) In both LiFEA and LiETFSI, the ethylene oxide moiety efficiently captures Li+, resulting in a self-folded structure and high T+ around 0.8. ii) For LiFEA, a Li-N bond (2.069 Å) is revealed by single crystal X-ray diffraction, indicating that the FEA anion possesses a high donor number (DN) and thus an intensive interphase "self-cleaning" function for an ultra-thin and compact SEI. iii) Starting from LiFEA, an electron-withdrawing sulfone group is introduced near the N atom. The distance of Li-N is tuned from 2.069 Šin LiFEA to 4.367 Šin LiETFSI. This alteration enhances ionic separation, achieves a more balanced DN, and tunes the self-cleaning intensity for a reinforced SEI. Consequently, the fast charging/discharging capability of LMBs is progressively improved. This rationally tuned anion chemistry reshapes the interactions among Li+, anions, and solvents, presenting new prospects for advanced LMBs.

The genome of the black-footed cat: Revealing a rich natural history and urgent conservation priorities for small felids.

Habitat degradation and loss of genetic diversity are common threats faced by almost all of today's wild cats. Big cats, such as tigers and lions, are of great concern and have received considerable conservation attention through policies and international actions. However, knowledge of and conservation actions for small wild cats are lagging considerably behind. The black-footed cat, Felis nigripes, one of the smallest felid species, is experiencing increasing threats with a rapid reduction in population size. However, there is a lack of genetic information to assist in developing effective conservation actions. A de novo assembly of a high-quality chromosome-level reference genome of the black-footed cat was made, and comparative genomics and population genomics analyses were carried out. These analyses revealed that the most significant genetic changes in the evolution of the black-footed cat are the rapid evolution of sensory and metabolic-related genes, reflecting genetic adaptations to its characteristic nocturnal hunting and a high metabolic rate. Genomes of the black-footed cat exhibit a high level of inbreeding, especially for signals of recent inbreeding events, which suggest that they may have experienced severe genetic isolation caused by habitat fragmentation. More importantly, inbreeding associated with two deleterious mutated genes may exacerbate the risk of amyloidosis, the dominant disease that causes mortality of about 70% of captive individuals. Our research provides comprehensive documentation of the evolutionary history of the black-footed cat and suggests that there is an urgent need to investigate genomic variations of small felids worldwide to support effective conservation actions.

Asymmetric Trihalogenated Aromatic Lithium Salt Induced Lithium Halide Rich Interface for Stable Cycling of All-Solid-State Lithium Batteries.

Solid polymer electrolytes (SPEs) are the key components for all-solid-state lithium metal batteries with high energy density and intrinsic safety. However, the low lithium ion transference number (t+) of a conventional SPE and its unstable electrolyte/electrode interface cannot guarantee long-term stable operation. Herein, asymmetric trihalogenated aromatic lithium salts, i.e., lithium (3,4,5-trifluorobenzenesulfonyl)(trifluoromethanesulfonyl)imide (LiFFF) and lithium (4-bromo-3,5-difluorobenzenesulfonyl)(trifluoromethanesulfonyl)imide (LiFBF), are synthesized for polymer electrolytes. They exhibit higher t+ values and better compatibility with Li metal than conventional lithium bis(trifluoromethanesulfonyl) imide (LiTFSI). Due to the trihalogenated aromatic anions, LiFFF- and LiFBF-based electrolytes are prone to generate an LiF- and LiBr-rich solid electrolyte interphase (SEI), therefore increasing the stability of the solid electrolyte/anode interface. Particularly, LiFBF could induce a LiF/LiBr hybrid SEI, where LiF shows a high Young's modulus and high surface energy for homogenizing Li ion flux and LiBr exhibits an extremely low Li ion diffusion barrier in the SEI layer. As a result, the Li/Li symmetric cells could remain stable for more than 1200 h without a short circuit and the LiFePO4/Li batteries showed superb electrochemical performance over 1200 cycles at 1 C. This work provides valuable insights from the perspective of lithium salt molecular structures for high-performance all-solid-state lithium metal batteries.

Tuning and Balancing the Donor Number of Lithium Salts and Solvents for High-Performance Li Metal Anode.

The low reversibility of Li deposition/stripping in conventional carbonate electrolytes hinders the development of lithium metal batteries. Herein, we proposed a combination of solvents with a moderate donor number (DN) and LiNO3 as the sole salt, which has rarely been attempted due to its low solubility or dissociation degree in common solvents. It is found that the DN value of solvents is highly correlated to the reversibility of Li deposition behavior when LiNO3 is applied as the sole salt. The combination of LiNO3 and solvents with moderate DN behaves like a quasi-concentrated electrolyte even at a common or moderate concentration, while neither the solvents with poor solubility and low dissociation for LiNO3 (which usually corresponds to a low DN) nor the solvents with high dissociation for LiNO3 (which usually corresponds to an overly high DN) can achieve a high reversibility for low conductivity or excessive solvent decomposition. As a result, a Coulombic efficiency as high as 99.6% for Li deposition/stripping is achieved with the optimized combination. We believe this work will give a better understanding of the role of anions and solvents in the regulation of the solvation structure, and DN can be utilized as an important guideline to sieve suitable solvents for LiNO3 as the main salt to exhibit intriguing properties beyond traditional cognition.

Fluorinated Carbamate-Based Electrolyte Enables Anion-Dominated Solid Electrolyte Interphase for Highly Reversible Li Metal Anode.

Li metal is regarded as the most promising battery anode to boost energy density. However, being faced with the hostile compatibility between the Li anode and traditional carbonate electrolyte, its large-scale industrialization has been in a distressing circumstance due to severe dendrite growth caused by unsatisfying solid electrolyte interphase (SEI). With this regard, accurate control over the composition of the SEI is urgently desired to tackle the electrochemical and mechanical instability at the electrolyte/anode interface. Herein, we report a rationally designed fluorinated carbamate-based electrolyte employing LiNO3 as one of the main salts to induce the preferable anion decomposition to achieve a homogeneous and inorganic (LiF, Li3N, Li2O)-rich SEI. Thus, this electrolyte achieves a high Coulombic efficiency of 99% of the Li metal anode, a stable cycling over 1000 h for Li|Li symmetric cells, more than 100 cycles in 40-µm-thin Li|high-loading-NCM811 full batteries, and >50 cycles in Cu|LiFePO4 pouch cells, which is a promising electrolyte for highly reversible Li metal batteries.

Tuning the Li+ Solvation Structure by a "Bulky Coordinating" Strategy Enables Nonflammable Electrolyte for Ultrahigh Voltage Lithium Metal Batteries.

In battery electrolyte design principles, tuning Li+ solvation structure is an effective way to connect electrolyte chemistry with interfacial chemistry. Although recent proposed solvation tuning strategies are able to improve battery cyclability, a comprehensive strategy for electrolyte design remains imperative. Here, we report a solvation tuning strategy by utilizing molecular steric effect to create a "bulky coordinating" structure. Based on this strategy, the designed electrolyte generates an inorganic-rich solid electrolyte interphase (SEI) and cathode-electrolyte interphase (CEI), leading to excellent compatibility with both Li metal anodes and high-voltage cathodes. Under an ultrahigh voltage of 4.6 V, Li/NMC811 full-cells (N/P = 2.0) hold an 84.1% capacity retention over 150 cycles and industrial Li/NMC811 pouch cells realize an energy density of 495 Wh kg-1. This study provides innovative insights into Li+ solvation tuning for electrolyte engineering and offers a promising path toward developing high-energy Li metal batteries.

Age at menarche and polycystic ovary syndrome: A Mendelian randomization study.

OBJECTIVE: The authors aimed to use a large two-sample Mendelian randomization (MR) study to reveal the causality between age at menarche (AAM) and polycystic ovary syndrome (PCOS) incidence. METHODS: The authors collected summary statistics from the hitherto largest genome-wide association studies conducted in AAM and PCOS in the same ancestry. MR with inverse variance weighting was conducted as the main analysis method, while weighted median and MR-Egger regression were used for comprehensive analysis. As for pleiotropy detection, inverse variance weighting, MR-Egger regression, Mendelian Randomization Pleiotropy Residual Sum and Outlier, as well as leave-one-out analysis were used to detect pleiotropy. Risk factor analysis was conducted to investigate the underlying mechanisms linking AAM to PCOS. RESULTS: Each standard deviation increment in AAM was associated with a significantly lower incidence of PCOS (odds ratio, 0.86 [95% confidence interval, 0.75-0.98]). After adjustment in horizontal pleiotropy by eliminating four outliers, this pathogenic association was still statistically detected. All pleiotropy indexes were without statistical differences, which suggested the conclusions were robust. It showed the causal association between later AAM and lower body mass index, lower fasting insulin level and insulin resistance. CONCLUSION: Our MR analysis verified that a slightly later onset age (15 to 18 years) at menarche could reduce the risk of PCOS. A more comprehensive investigation in a prospective setting is strongly advised.

Adoptive Treg therapy with metabolic intervention via perforated microneedles ameliorates psoriasis syndrome.

Regulatory T (Treg) cells underlie multiple autoimmune disorders and potentialize an anti-inflammation treatment with adoptive cell therapy. However, systemic delivery of cellular therapeutics often lacks tissue targeting and accumulation for localized autoimmune diseases. Besides, the instability and plasticity of Treg cells also induce phenotype transition and functional loss, impeding clinical translation. Here, we developed a perforated microneedle (PMN) with favorable mechanical performance and a spacious encapsulation cavity to support cell survival, as well as tunable channels to facilitate cell migration for local Treg therapy of psoriasis. In addition, the enzyme-degradable microneedle matrix could release fatty acid in the hyperinflammatory area of psoriasis, enhancing the Treg suppressive functions via the fatty acid oxidation (FAO)-mediated metabolic intervention. Treg cells administered through PMN substantially ameliorated psoriasis syndrome with the assistance of fatty acid-mediated metabolic intervention in a psoriasis mouse model. This tailorable PMN could offer a transformative platform for local cell therapy to treat a variety of diseases.

Vision-Based Structural Modal Identification Using Hybrid Motion Magnification.

As a promising alternative to conventional contact sensors, vision-based technologies for a structural dynamic response measurement and health monitoring have attracted much attention from the research community. Among these technologies, Eulerian video magnification has a unique capability of analyzing modal responses and visualizing modal shapes. To reduce the noise interference and improve the quality and stability of the modal shape visualization, this study proposes a hybrid motion magnification framework that combines linear and phase-based motion processing. Based on the assumption that temporal variations can represent spatial motions, the linear motion processing extracts and manipulates the temporal intensity variations related to modal responses through matrix decomposition and underdetermined blind source separation (BSS) techniques. Meanwhile, the theory of Fourier transform profilometry (FTP) is utilized to reduce spatial high-frequency noise. As all spatial motions in a video are linearly controllable, the subsequent phase-based motion processing highlights the motions and visualizes the modal shapes with a higher quality. The proposed method is validated by two laboratory experiments and a field test on a large-scale truss bridge. The quantitative evaluation results with high-speed cameras demonstrate that the hybrid method performs better than the single-step phase-based motion magnification method in visualizing sound-induced subtle motions. In the field test, the vibration characteristics of the truss bridge when a train is driving across the bridge are studied with a commercial camera over 400 m away from the bridge. Moreover, four full-field modal shapes of the bridge are successfully observed.

A multi-granularity convolutional neural network model with temporal information and attention mechanism for efficient diabetes medical cost prediction.

As the cost of diabetes treatment continues to grow, it is critical to accurately predict the medical costs of diabetes. Most medical cost studies based on convolutional neural networks (CNNs) ignore the importance of multi-granularity information of medical concepts and time interval characteristics of patients' multiple visit sequences, which reflect the frequency of patient visits and the severity of the disease. Therefore, this paper proposes a new end-to-end deep neural network structure, MST-CNN, for medical cost prediction. The MST-CNN model improves the representation quality of medical concepts by constructing a multi-granularity embedding model of medical concepts and incorporates a time interval vector to accurately measure the frequency of patient visits and form an accurate representation of medical events. Moreover, the MST-CNN model integrates a channel attention mechanism to adaptively adjust the channel weights to focus on significant medical features. The MST-CNN model systematically addresses the problem of deep learning models for temporal data representation. A case study and three comparative experiments are conducted using data collected from Pingjiang County. Through experiments, the methods used in the proposed model are analyzed, and the super contribution of the model performance is demonstrated.

Glucose-responsive microneedle patch for closed-loop dual-hormone delivery in mice and pigs.

Insulin and glucagon secreted from the pancreas with dynamic balance play a vital role in regulating blood glucose levels. Although distinct glucose-responsive insulin delivery systems have been developed, the lack of a self-regulated glucagon release module limits their clinical applications due to the potential risk of hypoglycemia. Here, we describe a transdermal polymeric microneedle patch for glucose-responsive closed-loop insulin and glucagon delivery to achieve glycemic regulation with minimized risk of hypoglycemia. The glucose-responsive phenylboronic acid units can bind to glucose to reversibly shift the net charge (from positive to negative) of the entire polymeric matrix within microneedles. Therefore, the release ratio of the negatively charged insulin and the positively charged glucagon analog from the patch can be dynamically tuned upon the fluctuation of blood glucose levels to realize glycemic homeostasis. In both chemically induced type 1 diabetic mouse and minipig models, this glucose-responsive dual-hormone microneedle patch demonstrated tight long-term regulation in blood glucose levels (>24 hours in minipigs).

Novel Urea-Based Molecule Functioning as a Solid Electrolyte Interphase Enabler and LiPF6 Decomposition Inhibitor for Fast-Charging Lithium Metal Batteries.

The practical application of lithium metal batteries is impeded by the growth of dendrites and decomposition of electrolytes especially at high temperature in normal carbonate-based electrolytes. Herein, a novel urea-based molecule, 1,3-dimethyl-2-imidazolidinone (DMI), with a high donor number is proposed, which exhibits an extraordinary solubility of LiNO3 of over 5 M. As a result, a sufficient amount of LiNO3 is readily introduced into the carbonate electrolytes with DMI as an additive, and an average coulombic efficiency of 99.1% for lithium plating/stripping is achieved due to a stable solid electrolyte interphase (SEI) rich in inorganic-rich lithium salts. The Li||Li symmetric cell achieves a stable operation for over 2500 h at 0.5 mA cm-2 and 1 mAh cm-2, and a granular shape of deposited Li metal is still preserved even at a high current density of 10 mA cm-2. Besides, the decomposition of LiPF6 is inhibited benefiting from its enhanced dissociation after the addition of DMI/LiNO3 and DMI's function as a PF5 scavenger. Consequently, the Li||LiFePO4 cell succeeds to achieve an excellent capacity retention of 95.6% after 2200 cycles at a high rate of 5C, and a stable operation is realized at a high temperature of 60 °C even under harsh conditions (45 µm ultrathin Li and ∼1.5 mAh cm-2 LiFePO4). This work enriches the solvents and additives pool for stable and high-performance lithium metal batteries and will shed light on future developments of advanced battery electrolytes.

Rationally Designed Fluorinated Amide Additive Enables the Stable Operation of Lithium Metal Batteries by Regulating the Interfacial Chemistry.

A fluorinated amide molecule with two functional segments, namely, an amide group with a high donor number to bind lithium ions and a fluorine chain to expel carbonate solvents and mediate the formation of LiF, was designed to regulate the interfacial chemistry. As expected, the additive preferably appears in the first solvation sheath of lithium ions and is electrochemically reduced on the anode, and thus an inorganic-rich solid electrolyte interphase is generated. The morphology of deposited lithium metal evolves from brittle dendrites into a granular shape. Consequently, the Li||LiFePO4 cell shows an excellent capacity retention of 92.7% at a high rate of 5 C after 800 cycles. Besides, the Li||LiNi0.8Co0.1Mn0.1O2 cell succeeds to maintain 98.1% of the initial capacity after 100 cycles at 1 C. Our designing of N,N-diethyl- 2,3,3,3-tetrafluoropropionamide (denoted as DETFP) highlights the importance of a "high donor number" and may shed light on the design principles of electrolytes for high performance batteries.

Which type of chromosomal mosaicism is compatible for embryo transfer: a systematical review and meta-analysis.

PURPOSE: Chromosomal mosaicism becomes a common phenomenon in Preimplantaion genetic testing (PGT). This meta-analysis was conducted to study which feature of chromosomal mosaicism was compatible for embryo transfer. METHODS: After searching the database PubMed, Embase, CCTR and related reviews up until May 2021. Two reviewers extracted relevant information and assessed study quality by the Newcastle-Ottawa scale independently. Summary Odd Radios (OR) were calculated using fixed- or random-effects models for clinical outcomes. A network meta-analysis compared the clinical outcomes of different chromosomes. RESULTS: A total of six studies with 1,106 cycles of single mosaic embryo transferred were included. Significant results of implantation rate (IR), miscarriage rate (MR), and ongoing pregnancy/live birth rate (OP/LBR) were observed when comparing embryos with mosaicism level < 50% and ≥ 50% [OR 1.42, 95% CI (1.06, 1.89); OR 0.45, 95% CI (0.27, 0.75); OR 1.74, 95% CI (1.28, 2.37)], and embryos with mosaicism with only affecting segmental chromosome(s) and only involving whole chromosome(s) [OR 1.31, 95% CI (1.01, 1.71); OR 0.57, 95% CI (0.36, 0.93); OR 1.51, 95% CI (1.15, 2.00)]. Embryos with only mosaic gains or losses had significant higher IR and OP/LBR than complex mosaicism [Gains vs complex: OR 1.75, 95% CI (1.20, 2.54); OR 1.73, 95% CI (1.16, 2.58). Losses vs complex: OR 1.90, 95% CI (1.34, 2.71); OR 2.10, 95% CI (1.44, 3.07)]. Mosaic embryos with only one chromosome involved had significant favorable outcomes of IR and OP/LBR than with three or more chromosomes involved [OR 1.76, 95% CI (1.23, 2.52); OR 1.86, 95% CI (1.25,2.78)]. Chr. 7, Chr. 2, Chr. 1, Chr. 18, Chr. 11, Chr. X, Chr. 13, Chr. 14, Chr. 12, and Chr. 9 were considered as prioritized chromosomes of mosaic embryos for transfer. CONCLUSIONS: This analysis support the embryos with mosaicism level ≥ 50%, whole chromosome(s) involved, multiple mosaic abnormalities were associated with worse pregnancy outcomes. Mosaicism level of 50% could be used as a threshold to assess the mosaic embryos.

Bad to All? A Novel Way to Analyze the Effects of Fee-for-Service on Multiple Grades Hospitals Operation Outcomes.

It is a consensus that Fee-for-Service (FFS) is a traditional medical insurance payment scheme with significant disadvantages, namely the waste of health care resources. However, the majority of the prior works that draw such conclusions from the perspective of social welfare while analyzing the impacts of FFS on operation outcomes of hospitals still lack attention from the existing literature, considering the fact that the majority of public hospitals are self-founding. Under this motivation, we collected operation data of 301 public hospitals with different grades (grade II and III) in central China. Here, we present a novel statistical evaluation framework on the impact of FFS on hospital operation outcomes from four dimensions (financial income, efficiency, medical service capacity, and sustainability) using fixed-effects multivariate regression. With verification by the robustness test, our results indicate that: (i) The classification of the hospital (COH) significantly affected the impacts of FFS on hospitals' operations. (ii) For grade III hospitals, FFS leads to higher financial income, medical service capacity (MSC) and longer length-of-stay (LOS). (iii) However, as for grade II hospitals, hospitals with FFS adoptions achieve lower financial income, lower MSC and shorter LOS, which violates the common sense from previous works. (iv) FFS has a significant negative impact on public hospital's sustainable development; however, there is lack of evidence showing that sustainability would be affected by the interaction effects between FFS and COH. We believe these new findings from the perspective of hospital operation provide insights and could serve as a reference for the healthcare payment hierarchical reform by COH in low and middle-income countries (LMICs), which are going through the primary stage of the healthcare reform.

Impact of preimplantation genetic testing on obstetric and neonatal outcomes: a systematic review and meta-analysis.

OBJECTIVE: To investigate whether preimplantation genetic testing (PGT) increases the risk of adverse obstetric and neonatal outcomes. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Pregnancies achieved after PGT or in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). INTERVENTION(S): Systematic search of databases until December 2020 with cross-checking of references from relevant articles in English. MAIN OUTCOME MEASURE(S): Obstetric and neonatal outcomes after PGT and IVF/ICSI, including mean birth weight, low birth weight, very low birth weight (VLBW), mean gestational age at birth, preterm birth, very preterm birth, birth defects, intrauterine growth retardation (IUGR), sex ratio, cesarean section, hypertensive disorders of pregnancy, gestational diabetes mellitus, placenta disorder (placenta previa, placenta abruption, placenta accreta), and preterm premature rupture of membranes. RESULT(S): Ultimately, a total of 785,445 participants were enrolled in this meta-analysis, and these participants were divided into a PGT group (n = 54,294) and an IVF/ICSI group (n = 731,151). The PGT pregnancies had lower rates of low birth weight (risk ratio [RR] 0.85, 95% confidence interval [CI] 0.75 to 0.98), VLBW (RR 0.52, 95% CI 0.33 to 0.81), and very preterm births (RR 0.55, 95% CI 0.42 to 0.70) than those of IVF/ICSI pregnancies. However, the PGT group had a higher rate of the obstetric outcome of hypertensive disorders of pregnancy (RR 1.30, 95% CI 1.08 to 1.57). The PGT did not increase the risk of other adverse obstetric and neonatal outcomes, such as those associated with mean birth weight, mean gestational age at birth, birth defects, IUGR, sex ratio, cesarean section, gestational diabetes mellitus, placental disorder (placenta previa, placenta abruption, placenta accreta), or preterm premature rupture of membranes. We performed subgroup analysis with only blastocyst biopsies and found that PGT with blastocyst biopsies was associated with a lower rate of VLBW (RR 0.55, 95% CI 0.31 to 0.95). The PGT with blastocyst biopsies did not increase the risk of other adverse obstetric and neonatal outcomes. Additionally, we performed subgroup analysis with only frozen-thawed embryo transfer cycles, and we found that PGT pregnancies were associated with a lower rate of VLBW (RR 0.55, 95% CI 0.31 to 0.97), a lower rate of cesarean birth (RR 0.90, 95% CI 0.82 to 0.99), a higher rate of preterm birth (RR 1.10, 95% CI 1.02 to 1.18), and a higher rate of IUGR (RR 1.21, 95% CI 1.06 to 1.38) than those of IVF/ICSI pregnancies. The PGT with frozen-thawed embryo transfer did not increase the risk of other adverse obstetric and neonatal outcomes. CONCLUSION(S): The pooled analysis suggested that PGT did not increase the risk of adverse obstetric outcomes. The association between PGT and a higher risk of IUGR requires further investigation.

Storage Time of Cryopreserved Embryos and Pregnancy Outcomes: A Dose-Response Meta-Analysis.

Purpose Cryopreservation techniques have become an essential part of assisted reproduction technology. Embryos may be cryopreserved for several years before transfer, and the safety of long-term cryopreservation needs to be considered. This dose-response meta-analysis was conducted to evaluate whether there were dose-response relationships between the storage time of cryopreserved embryos and pregnancy outcomes such as survival rate, implantation rate, miscarriage rate, clinical pregnancy rate, and congenital malformation rate. Methods After searching the databases PubMed, Embase, MEDLINE, CCRT and related reviews up until June 4, 2020, seven studies were included for analysis. Two reviewers extracted the relevant information and independently assessed the study quality using the Newcastle-Ottawa scale. Potential linear or non-linear dose-response relationships were assessed with a random-effect dose-response meta-analysis. Results No dose-response association was found between duration of embryo cryostorage and survival rate, implantation rate, miscarriage rate, clinical pregnancy rate or congenital malformation rate. Conclusion The interval between the start of embryo cryopreservation and frozen/thawed embryo transfer does not influence pregnancy outcomes.