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Fall from ladders is increasingly identified as a significant cause of injury and mortality, yet large-scale research into ladder fall outcomes and trends is limited.To explore the nature and severity of injuries resulting from ladder falls and to determine predictors of Injury Severity Score (ISS) and 6-month mortality.Data were obtained from the New South Wales (NSW) Trauma Registry, Admitted Patient Data Collection and Registry of Births, Deaths, and Marriages on patients aged 15 and over who had major trauma from a ladder fall and were admitted to hospital between January 1st, 2012, and July 31st, 2019. Data linkage and descriptive statistics were carried out alongside bivariate and multivariable regression analysis.963 patients injured after ladder falls were identified. The mean age was 61.9 years (SD 14.2), 91.0% were male, and 489 (50.8%) were born in Australia. The height of fall was between one and five meters in 827 (86.2%) patients, and the place of fall was home and residential places in 27.5%. The most common body areas injured were the head (26.5%), spine (21.2%) and thorax (20.6%), and the median injury severity score was 17. The median length of stay of patients' in-hospital and intensive care unit was six days and two days, respectively. Six months post-discharge mortality was 6.4%. The unadjusted association between the presence of comorbidities or socio-economic class and ISS or mortality was not statistically significant. Increasing ISS was found to be associated with increasing age (Estimate (Est), 15.2; 95% Confidence Interval (CI), 12.3-18.1) and a fall height greater than five metres (Est, 5.8; CI, 3.2-8.4). Mortality was found to be associated with increasing age (Odds ratio (OR), 1.06; CI, 1.03-1.08) and increasing ISS (OR, 1.19; CI, 1.15-1.24).People presenting to the hospital after falling from a ladder were predominately male, aged over 60 and had fallen in a residential setting. Increasing age and fall height are associated with more severe injuries.

Polystichum suiyangense (Dryopteridaceae), a new species from Suiyang County, Guizhou, China, is described and illustrated. It is a member of P. sect. Sphaenopolystichum and similar to P. auriculum, P. bifidum, and P. martinii, but differs from them in its frond texture, leaf color, scales on petiole and rachis, pinna shape, and pinna apex. The new species is currently known only from the type locality and is classified as CR (critically endangered) following the IUCN criteria.

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases characterized by cognitive deficits and dementia. AD entails predominant pathological characteristics including amyloid beta (Aβ) plaque formation, neurofibrillary entanglements, and brain atrophy, which gradually result in cognitive dysfunctions. Studies showed that these pathological changes are found in a myriad of brain structures, including the claustrum (CLA), a nucleus that penetrates deeply into the brain and is extensively interconnected to various brain structures. The CLA modulates many aspects of cognitive functions, with attention, executive function, visuospatial ability, language, and memory in particular. It is also implicated in multiple neuropsychiatric disorders, of which one worthy of particular attention is AD-related cognitive impairments. To inspire novel AD treatment strategies, this review has summarized the CLA functionality in discriminative cognitive dysfunctions in AD. And then propose an array of potential mechanisms that might contribute to the cognitive impairments caused by an abnormal CLA physiology. We advocate that the CLA might be a new promising therapeutic target in combination with existing anti-AD drugs and brain stimulation approaches for future AD treatment.

Nickel–cobalt alloys were prepared by alloy electrodeposition with a sulfamate bath, and the mechanical properties on the micro-scale were evaluated for the application as micro-components in miniaturized electronic devices. Nickel bromide and a commercially available surface brightener were used as the additives. The cobalt content increased from 21.5 to 60.1 at.% after addition of nickel bromide into the bath, and the grain size refined from 21.1 to 13.2 nm when the surface brightener was used. The mechanical properties on the micro-scale were evaluated by micro-compression test using micro-pillar type specimens fabricated by a focused ion beam system to take the sample size effect into consideration. The yield strength of the nickel–cobalt alloy having an average grain size at 13.9 nm and cobalt content of 66.6 at.% reached 2.37 GPa, revealing influences from the sample size, grain boundary strengthening, and solid solution strengthening effects.

RTK expression profiles in normal, early HCC, and advanced HCC tissues.

Summary of the xenograft and tumor-sphere formation assays

Purpose:Hepatitis promotes the development and recurrence of hepatocellular carcinoma (HCC). Receptor tyrosine kinases (RTK) play critical roles in the development of many cancers. We explored the potential roles of RTKs in hepatitis-related liver cancers.Experimental Design:We conducted loss-of-function screening to elucidate the roles of RTKs in the development of HCC in vitro and in vivo.Results:Many RTKs were coexpressed in HCC and were involved in tumor development and growth. Of these, TYRO3 promoted tumor growth and was clinically associated with hepatitis activity and poor prognosis. In mice, chemical-induced hepatitis transcriptionally activated Tyro3 expression via IL-6/IL6R–STAT3 signaling. Moreover, hepatitis-associated apoptotic cells facilitated the presentation of GAS6, a TYRO3 ligand, to further activate TYRO3-mediated signaling. Furthermore, TYRO3 activation elicited intracellular SRC- and STAT3 signaling. In mice, hepatitis and Tyro3 synergistically promoted HCC development. Silencing TYRO3 expression or inhibiting its kinase activity suppressed xenograft HCC growth in nude mice.Conclusions:Many RTKs are simultaneously involved in HCC development. Hepatitis exerts dual effects on the activation of TYRO3-mediated signaling in HCC cells, which further elicits the “TYRO3–STAT3–TYRO3” signaling loop to facilitate tumor growth. Our findings unveil a previously unrecognized link between RTKs and hepatitis-associated HCC and suggest TYRO3 as a marker and therapeutic target for the HCCs with higher hepatitis activity.

Supplemental Figure S2 to S11

Protein- expression profiles of the RTK family members in the hepatocytes and hepatoma cells

Supplemental information of Materials and Methods

Correlation between TYRO3 level and clinicopathologic features in 120 HCC patients

Many intensive care unit patients who undergo endotracheal extubation experience extubation failure and require reintubation. Because of the high mortality rate associated with reintubation, postextubation respiratory management is crucial, especially for high-risk populations. We conducted the present study to compare the effectiveness of oxygen therapy administered using high-flow nasal cannulae (HFNC) and noninvasive positive pressure ventilation (NIPPV) in preventing reintubation among patients receiving prolonged mechanical ventilation (PMV). This single-center, prospective, unblinded randomized controlled trial was at the respiratory care center (RCC). Participants were randomized to an HFNC group or an NIPPV group (20 patients in each) and received noninvasive respiratory support (NRS) administered using their assigned method. The primary outcome was reintubation within7 days after extubation. None of the patients in the NIPPV group required reintubation, whereas 5 (25%) of the patients in the HFNC group required reintubation (P = 0.047). The 90-day mortality rates of the NIPPV and HFNC groups (four patients [20%] vs. two patients [10%], respectively) did not differ significantly. No significant differences in length of RCC stay, length of hospital stay, time to liberation from NRS, and ventilator-free days at 28-day were identified. The time to event outcome analysis also revealed that the risk of reintubation in the HFNC group was higher than that in the NIPPV group (P = 0.018). Although HFNC is becoming increasingly common as a form of postextubation NRS, HFNC may not be as effective as NIPPV in preventing reintubation among patients who have been receiving PMV for at least 2 weeks. Additional studies evaluating HFNC as an alternative to NIPPV for patients receiving PMV are warranted.ClinicalTrial.gov ID: NCT04564859; IRB number: 20160901R.Trial registration: ClinicalTrial.gov (https://clinicaltrials.gov/ct2/show/NCT04564859).

BackgroundThe aim of our study was to externally validate the predictive capability of five developed coronavirus disease 2019 (COVID-19)-specific prognostic tools, including the COVID-19 Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), Shang COVID severity score, COVID-intubation risk score-neutrophil/lymphocyte ratio (IRS-NLR), inflammation-based score, and ventilation in COVID estimator (VICE) score.MethodsThe medical records of all patients hospitalized for a laboratory-confirmed COVID-19 diagnosis between May 2021 and June 2021 were retrospectively analyzed. Data were extracted within the first 24 h of admission, and five different scores were calculated. The primary and secondary outcomes were 30-day mortality and mechanical ventilation, respectively.ResultsA total of 285 patients were enrolled in our cohort. Sixty-five patients (22.8%) were intubated with ventilator support, and the 30-day mortality rate was 8.8%. The Shang COVID severity score had the highest numerical area under the receiver operator characteristic (AUC-ROC) (AUC 0.836) curve to predict 30-day mortality, followed by the SEIMC score (AUC 0.807) and VICE score (AUC 0.804). For intubation, both the VICE and COVID-IRS-NLR scores had the highest AUC (AUC 0.82) compared to the inflammation-based score (AUC 0.69). The 30-day mortality increased steadily according to higher Shang COVID severity scores and SEIMC scores. The intubation rate exceeded 50% in the patients stratified by higher VICE scores and COVID-IRS-NLR score quintiles.ConclusionThe discriminative performances of the SEIMC score and Shang COVID severity score are good for predicting the 30-day mortality of hospitalized COVID-19 patients. The COVID-IRS-NLR and VICE showed good performance for predicting invasive mechanical ventilation (IMV).

Guangxia longlina An, Chen & Shi, sp. nov. Description. Male. Body small, thin. Fastigium verticis conical, apex rounded, with longitudinal sulcus on dorsal surface. Compound eyes globular, protruding forward. Frons slightly sloping backward. Apical segment of maxillary palpus approximately equated in length with subapical segment, apex swollen and rounded. Pronotum slightly elongate backward, with median carina, anterior margin nearly straight, posterior margin rounded; lateral lobe longer than deep, humeral sinus absent. Thoracic auditory spiracle exposed, oval. Tegmina only reaching apex of abdomen, tapering, apices slightly and obliquely truncated; hind wings slightly shorter than tegmina. All femora without spines on ventral surfaces. Procoxa with 1 spine; protibia with 6 spines on each side of ventral surface; tibial tympana oval, open on both sides. Mesotibia with 5–6 spines on each side of ventral surface. Genicular lobe of postfemora with apex rounded; posttibia with 23–27 spines on both sides of dorsal surface, bearing a pair of dorsal apical spurs and 2 pairs of ventral apical spurs. Posterior margin of male tenth abdominal tergite concave, with a pair of posterior processes branching from base to apex. Epiproct triangular. Cercus with 1 inner spinous process on middle area of ventral surface; apex incurved, with 2 branches, dorsal one longer than ventral one. Genitalia with dorsal and ventral lobes; dorsal lobe positioned between the cerci, elongated, with dorsal surface concave, apex rounded and slightly downcurved; ventral lobe positioned between cerci and subgenital plate, basal 2/3 extending into a semicircle on both sides, apex nearly rectangular, posterior margin upcurved, with middle area concave. S ubgenital plate nearly rectangular, longer than wide. Styli short, positioned on apex of subgenital plate. Coloration. Body slightly brown or slightly green. Antennae brown, with sparse black rings. Compound eyes brown. Tegmina with black spots. Apex of genicular lobe black. Female. General appearance is similar to that of male. Cerci conical, apices acute. S ubgenital plate nearly rhombic, with posterior margin rounded. Ovipositor slightly upcurved, dorsal and ventral margins smooth, ventral valvulae with apices hooked. Material examined. Holotype: ♁, Jinzhongshan, Longlin, Guangxi, China, 21 August, 2022, coll. Meng An. Paratypes: 3♁ 3♀, Jinzhongshan, Longlin, Guangxi, China, 17 August, 2022, coll. Meng An; 1♁ 1♀, Jinzhongshan, Longlin, Guangxi, China, 18 August, 2022, coll. Meng An; 4♀, Jinzhongshan, Longlin, Guangxi, China, 19 August, 2022, coll. Meng An; 3♁ 1♀, Jinzhongshan, Longlin, Guangxi, China, 20 August, 2022, coll. Meng An; 3♁ 3♀, the other data as holotype. Measurements (mm). Body: ♁7.0–8.3, ♀ 7.3–8.9; pronotum: ♁3.9–4.2, ♀ 3.9–4.0; tegmen: ♁6.5–7.1, ♀ 7.0–7.9; postfemora: ♁8.5–9.0, ♀ 9.0–10.0; ovipositor: ♀ 8.0–9.8. Distribution. China (Guangxi). Etymology. The name of the new species is derived from its type locality (Longlin, Guangxi, China). Discussion. The new species resembles Aphlugiolopsis Wang, Liu & Li, 2015, but differs in: posterior margin of male tenth abdominal tergite concave, with a pair of posterior processes; styli positioned on apex of subgenital plate., Published as part of An, Meng, Chen, Chun & Shi, Fuming, 2023, One new genus and species of the tribe Meconematini (Orthoptera: Tettigoniidae: Meconematinae) from Guangxi, China, pp. 398-400 in Zootaxa 5227 (3) on pages 398-400, DOI: 10.11646/zootaxa.5227.3.8, http://zenodo.org/record/7518838, {"references":["Wang, H. Q., Liu, X. W. & Li, K. (2015) New taxa of Meconematini (Orthoptera: Tettigoniidae: Meconematinae) from Guangxi, China. Zootaxa, 3941 (4), 509 - 541. https: // doi. org / 10.11646 / zootaxa. 3941.4.3"]}

Guangxia An, Chen & Shi, gen. nov. Type species: Guangxia longlina An, Chen & Shi , sp. nov. Generic characters. Body small. Head hypognathous. Fastigium verticis conical, apex rounded, with longitudinal sulcus on dorsal surface. Compound eyes globular, protruding forward. Frons slightly sloping backward. Apical segment of maxillary palpus approximately equated in length with subapical segment, apex swollen and rounded. Pronotum slightly elongate backward, with a median carina; lateral lobe longer than deep, humeral sinus absent. Thoracic auditory spiracle exposed, peanut shape. Tegmina shorter, only reaching apex of abdomen, tapering, apices slightly and obliquely truncated; hind wings slightly shorter than tegmina. All femora without spines on ventral surfaces; tibial tympana open on both sides; genicular lobe of postfemora with apex rounded; posttibia with a pair of dorsal apical spurs and 2 pairs of ventral apical spurs. Posterior margin of male tenth abdominal tergite concave, with a pair of posterior processes; cercus with 2 branches; genitalia entirely sclerotized, exposed; subgenital plate with styli. Ovipositor slightly upcurved, ventral valvulae with apices hooked. Discussion. The new genus is similar to Aphlugiolopsis Wang, Liu & Li, 2015, but differs in: posterior margin of male tenth abdominal tergite concave, with a pair of posterior processes; styli positioned on apex of subgenital plate. It resembles Neocononicephora Gorochov, 1998, but differs in: posttibia with 3 pairs of apical spurs; male genitalia entirely sclerotized. Etymology. The name of the new genus is derived from its type locality (Longlin, Guangxi, China)., Published as part of An, Meng, Chen, Chun & Shi, Fuming, 2023, One new genus and species of the tribe Meconematini (Orthoptera: Tettigoniidae: Meconematinae) from Guangxi, China, pp. 398-400 in Zootaxa 5227 (3) on page 398, DOI: 10.11646/zootaxa.5227.3.8, http://zenodo.org/record/7518838, {"references":["Wang, H. Q., Liu, X. W. & Li, K. (2015) New taxa of Meconematini (Orthoptera: Tettigoniidae: Meconematinae) from Guangxi, China. Zootaxa, 3941 (4), 509 - 541. https: // doi. org / 10.11646 / zootaxa. 3941.4.3","Gorochov, A. V. (1998) New and little known Meconematinae of the tribes Meconematini and Phlugidini (Orthoptera: Tettigoniidae). Zoosystematica Rossica, 7 (1), 101 - 131."]}

Additional file 1. Supplementary figures 1–10.

Many-body localization (MBL) features long-time persistence of charge-density-like waves (CDWs) of local observables. Is it practical to commence from a modulated state pattern also for nonlocal quantum entanglement? Will such entanglement analogs of CDWs survive still in MBL? From a constituent viewpoint, a great deal of MBL is learnt from 1D spin or fermion systems where carriers are scatter particles. What about the situation when multiple interacting particles cluster in a random-potential background? To tackle these questions, we study symmetry-resolved entanglement entropy in disordered Bose-Hubbard (dBH) chain using numerical quantum quench dynamics. We concentrate on 2 types of inhomogeneous initial states after mapping out the energy-resolved dynamical phase diagram of the model. From time-evolving a line-shape initial product state, we find the sudden formation of robust entropy imbalance across different symmetry sectors, termed entanglement-channel wave (ECW). Intriguingly, ECW melts in MBL under strong-disorder limit. It is tempting to conjecture that melting of ECW and freezing of CDW are duo traits inherent to disorder-induced MBL. Further, by exploiting dynamical consequences of loading bosons onto one site, we find the possibility to realize an interaction-facilitated cluster localization unique to BH-type models at weak disorders. Together, the unraveled rich entanglement dynamics manifests the intrinsic complexity of dBH model from a jointly energy- and symmetry-resolved perspective.

Supplemental material, sj-docx-1-tct-10.1177_15330338211046432 for Effect of Programmed Death-Ligand 1 in Cancer-Associated Fibroblasts on Advanced Laryngeal Squamous Cell Carcinoma by Zhendong Yang, Jinxin Wang, Chun Chen, Peng Sun and Yafeng Yu in Technology in Cancer Research & Treatment

Supplementary Material 2

Additional file 1. Additional file of Correlation between C-Reactive Protein and Postoperative Mortality in Patients Undergoing Hip Fracture Surgery: A Meta-Analysis;Table S1 : Methodological quality of the included studies; Fig. S1: Funnel plot of the studies comparing preoperative CRP levels between the death and survival groups for a follow-up duration of ≥6 months.

Additional file 1: Supplement 1. Risk stratification based on the C-HUANAN-AML15 protocol.

Additional file 1. Appendix: Tables for RNA Family Groups and Further Performance Evaluation of ncRNA Benchmark.

Supplemental material, sj-docx-1-tam-10.1177_17588359231177016 for Concurrent chemotherapy using taxane plus cisplatin versus cisplatin alone in high-risk nasopharyngeal carcinoma patients with suboptimal response to induction chemotherapy by Ya-Ni Zhang, Yu-Pei Chen, Ji-Bin Li, Tai-Xiang Lu, Fei Han and Chun-Yan Chen in Therapeutic Advances in Medical Oncology

Supplementary Material 8: Supplementary Tables 1 - 4

Supplementary Material 1

Recent years have witnessed significant progress in developing efficient training and fast sampling approaches for diffusion models. A recent remarkable advancement is the use of stochastic differential equations (SDEs) to describe data perturbation and generative modeling in a unified mathematical framework. In this paper, we reveal several intriguing geometric structures of diffusion models and contribute a simple yet powerful interpretation to their sampling dynamics. Through carefully inspecting a popular variance-exploding SDE and its marginal-preserving ordinary differential equation (ODE) for sampling, we discover that the data distribution and the noise distribution are smoothly connected with an explicit, quasi-linear sampling trajectory, and another implicit denoising trajectory, which even converges faster in terms of visual quality. We also establish a theoretical relationship between the optimal ODE-based sampling and the classic mean-shift (mode-seeking) algorithm, with which we can characterize the asymptotic behavior of diffusion models and identify the score deviation. These new geometric observations enable us to improve previous sampling algorithms, re-examine latent interpolation, as well as re-explain the working principles of distillation-based fast sampling techniques.

Eye-controlled human-computer interaction (ECHCI) attracts attention for its human-centered, natural and direct operation characteristics. The most common ECHCI trigger motion is “gazing,” which causes Midas Touch problems, lowering usability and operation experience. This paper innovatively proposed using motion combinations based on blinking as the trigger of interactive objects (IOs). Trigger motions and IO design parameters were explored on the platform consisting of Tobii eye-tracker and computer vision kits. In the motion experiment, it was concluded 2-blinks could bring a low task load and high success rate of 95%. In the IO size experiment, the larger the IO diameter, the shorter the users’ response time and the higher users’ interaction success rate, and 55.5 mm was the optimal setting. Based on this, it was found a larger spacing could bring higher operation efficiency, and 33.3 mm was taken as the recommended value. Based on the conclusion above, an eye-controlled multimedia player prototype was built for usability evaluation, which showed an equally high efficiency compared to mouse-controlled HCI. The findings in this paper overcame Midas Touch issues and avoided the interference of unavoidable involuntary blinking, which brought a significant increase in system robustness and has a wide range of potential applications.

Supplemental material, sj-docx-1-tct-10.1177_15330338211046432 for Effect of Programmed Death-Ligand 1 in Cancer-Associated Fibroblasts on Advanced Laryngeal Squamous Cell Carcinoma by Zhendong Yang, Jinxin Wang, Chun Chen, Peng Sun and Yafeng Yu in Technology in Cancer Research & Treatment

Additional file 1: Fig. S1. Representative HPLC chromatograms of PET hydrolytic products generated by CtPL-DM and variants. Fig. S2. Overall structure of CtPL-DM and the wobbling TPA-binding Trp. Fig. S3. N-glycosylation sites of CtPL-DM-S155A. Fig. S4. The full-length protein sequence of CtPL-DM. Table S1. Mutagenesis oligonucleotides.

Additional file 1: Figure S1. The response of HCD-57 to stimulation of GM-CSF. (A) Parental HCD-57 and HCD-57 expressing wild-type SHP2, SHP2-D61Y, and SHP2-E76K were stimulated by increasing concentrations of GM-CSF for 72 hours and the cell viability was assessed by CCK-8. (B) Immunoblotting analysis of p-SHP2 and p-ERK in parental HCD-57 and HCD-57 expressing wild-type SHP2, SHP2-D61Y, and SHP2-E76K stimulated by GM-CSF for 10 minutes. Figure S2. Cell viability of HCD-57 expressing mutant SHP2 and parental cells treated by various concentrations of SHP099 or RMC-4550. HCD-57 was cultured in medium with EPO and HCD-57/SHP2-D61Y or -E76K cells were cultured without EPO. Cells were incubated with inhibitors for 48 hours the cell viability was assessed by CCK-8. Table S1. The FPKM values of specific genes detected by RNA-Seq.

A common wisdom posits that transports of conserved quantities across clean nonintegrable quantum systems at high temperatures are diffusive when probed from the emergent hydrodynamic regime. We show that this empirical paradigm may alter if the strong interaction limit is taken. Using Krylov-typicality and purification matrix-product-state methods, we establish the following observations for the strongly interacting version of the mixed-field Ising chain, a nonintegrable lattice model imitating the experimental Rydberg blockade array. Given the strict projection owing to the infinite density-density repulsion $V$, the chain's energy transport in the presence of a transverse field $g$ is superdiffusive at infinite temperature featured by an anomalous scaling exponent $\frac{3}{4}$, indicating the existence of a novel dynamical universality class. Imposing, in addition, a growing longitudinal field $h$ causes a drastic factorization of the whole Hilbert space into smaller subsectors, evidenced by the spectral parsing of the eigenstate entanglement. Being a consequence of this approximate symmetry, a superdiffusion-to-ballistic transport transition arises at $h\approx g$. Interestingly, all the above results persist for large but finite interactions and temperatures, provided that the strongly interacting condition $g,h\ll k_\textrm{B}T\ll V$ is fulfilled. Our predictions are verifiable by current experimental facilities., Comment: 5 pages, 4 figures

Supplementary Material 1: The online version contains supplementary material available.

Additional file 1.

Supplementary Material 1 - 7: Supplementary Figures 1 - 7. Supplementary Figure 1 - Quantification of GFAP+ labelling. Supplementary Figure 2 Altered mitochondrial mass in GFAP+ astrocytes in Alpers’ syndrome. Supplementary Figure 3 - Changes to astrocytic proteins in focal lesioned versus non- lesioned occipital cortex. Supplementary Figure 4 - Reactive astrogliosis in the frontal cortex in Alpers’ syndrome. Supplementary Figure 5 - Area of frontal cortical astrocytes. Supplementary Figure 6 - Mitochondrial oxidative phosphorylation protein deficiencies in frontal cortical astrocytes in Alpers’ syndrome. Supplementary Figure 7 - Altered expression of Kir4.1, AQP4 and glutamine synthetase in frontal cortical astrocytes in Alpers’ syndrome.

目的：藉由多元化教育訓練教材提升全自動全靜脈營養液(Total Parenteral Nutrition, TPN)調配機（Exacta-Mix 2400，簡稱EM2400）操作的正確性，進而改善TPN的檢驗不良率，確保醫療品質及達到病人安全之目標。 方法：運用品管手法PDCA概念改善TPN的檢驗不良率，使用5W2H手法進行現況分析，找出「TPN檢驗不良率高」之主要因，並擬定對策、設定初期目標為改善50%之TPN成品檢驗不良率平均數。 結果：使用多元化教材進行教學後，TPN成品檢驗不良率平均數由1.25%減少至0.32%，優於初期設定之目標0.625%，目標達成率148.8%、進步率74%。 結論：雖然EM2400可以協助TPN製程的品管，但裝機與原料藥的抽取仍需人力協助，如何減少人為疏失以維持TPN的品質穩定，將是確保醫療品質的關鍵步驟。 Objective: To improve the accuracy of operating the fully automated total parenteral nutrition (TPN) compounding system (Exacta-Mix 2400, EM2400) by using multiple instructional materials, with the anticipated outcomes of reducing the defect rate of TPN products and ensuring healthcare quality and patient safety. Methods: Applying Plan–Do–Check–Act (i.e., PDCA) quality assurance procedure to reduce the defect rate of TPN products. Using the 5W2H method to analyze the situation and identify the main reason for the high inspection defect rate of TPN products. Countermeasures can then be formulated with the goal of improving the average defect rate of TPN products by 50%. Results: After consulting multiple instructional materials, the average defect rate of TPN products was decreased from 1.25% to 0.32%, which was greater than the initial target of 0.625%. The target achievement rate was 148.8%, and the progress rate was 74%. Conclusion: Although EM2400 can support quality control in the TPN process, manual operation is still required for setting-up and withdrawing active pharmaceutical ingredients. Negligence reduction and the maintenance of TPN quality are the next critical steps to ensure healthcare quality. &nbsp

GALNT14-rs9679162 "TT" genotype is associated with favorable clinical outcomes in hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE). We investigated whether patients with GALNT14-rs9679162 "non-TT" unfavorable genotype benefited from chemoembolization plus sorafenib combination therapy.Intermediate stage HCC patients were recruited for GALNT14-rs9679162 genotyping before TACE. Patients with "TT" genotype received only TACE, labeled as TT (TACE) group. Patients with "non-TT" genotype ("GG" or "GT") were randomized to receive either TACE alone, labeled as Non-TT (TACE) group, or TACE plus sorafenib, labeled as Non-TT (TACE + Sora) group. The latter group received sorafenib 400 mg daily plus TACE.From October 2015 to April 2019, 103 HCC patients scheduled to receive chemoembolization were screened. Of them, 84 met inclusion criteria and were assigned to TT (TACE) (n = 25), Non-TT (TACE) (n = 30) and Non-TT (TACE + Sora) (n = 29) groups according to their GALNT14 genotypes. Repeated TACE sessions were performed on-demand and patients were followed until November 2020. It was found that TT (TACE) and Non-TT (TACE + Sora) patients had shorter time-to-complete response compared with that in Non-TT (TACE) patients (p 0.001 and 0.009, respectively). These two groups also had longer time-to-TACE progression (p 0.001 and 0.006, respectively) and longer progression-free survival (p = 0.001 and 0.021, respectively). However, TT (TACE) patients harbored longer overall survival compared with those in non-TT (TACE + Sora) and non-TT (TACE) patients (p = 0.028, 0.001, respectively).Combination of sorafenib and TACE for "non-TT" patients partially overcame the genetic disadvantage on treatment outcomes in terms of time-to-complete response, time-to-TACE progression and progression-free survival.ClinicalTrials.gov NCT02504983.

Wang, Bo, Wang, Ze-Huan, Chen, Chun-Ling, Xu, Wen-Fen, Sun, Qing-Wen (2021): Disporum dushanense (Colchicaceae), a new species from Guizhou, China. Phytotaxa 528 (2): 144-148, DOI: 10.11646/phytotaxa.528.2.8

Protein O-GlcNAcylation is a post-translational modification that links environmental stimuli with changes in intracellular signal pathways, and its disturbance has been found in neurodegenerative diseases and metabolic disorders. However, its role in the mesolimbic dopamine (DA) system, especially in the ventral tegmental area (VTA), needs to be elucidated. Here, we found that injection of Thiamet G, an O-GlcNAcase (OGA) inhibitor, in the VTA and nucleus accumbens (NAc) of mice, facilitated neuronal O-GlcNAcylation and decreased the operant response to sucrose as well as the latency to fall in rotarod test. Mice with DAergic neuron-specific knockout of O-GlcNAc transferase (OGT) displayed severe metabolic abnormalities and died within 4-8 weeks after birth. Furthermore, mice specifically overexpressing OGT in DAergic neurons in the VTA had learning defects in the operant response to sucrose, and impaired motor learning in the rotarod test. Instead, overexpression of OGT in GABAergic neurons in the VTA had no effect on these behaviors. These results suggest that protein O-GlcNAcylation of DAergic neurons in the VTA plays an important role in regulating the response to natural reward and motor learning in mice.

Objective In treating cervical esophageal fistula caused by trauma, tumor, surgery and other reasons, vacuum sealing drainage (VSD) used in order to speed up the healing and reduce the risk of recurrence. Methods In 24 cases of patients diagnosed with cervical esophageal fistula, the wound surface was opened completely to expose the fistula. Vacuum sealing drainage (VSD) devices were used to control infection, assisted by measures such as gastrointestinal decompression, prohibition of oral feeding, parenteral high nutritional support, and anti-inflammation, etc. Result 24 patients treated with vacuum sealing drainage (VSD) have been discharged from the hospital smoothly. After 3–6 months of follow-up and reexamination, all the cases were proved to heal well with no obvious sequelae and no recurrence of fistula. Conclusion For patients with cervical esophageal fistula, it is significant to apply the method of vacuum sealing drainage (VSD) for clinical treatment, which can effectively shorten the length of hospital stay, enable the patients to return to normal life earlier and enter the later stage of radiotherapy and chemotherapy as soon as possible. Hence it is worthy of clinical promotion.

BackgroundNicotinamide Adenine Dinucleotide (NAD) depletion is reported to be a potential treatment for B-cell Acute Lymphoblastic Leukemia (B-ALL), but the mechanism of NAD metabolism-related genes (NMRGs) in B-ALL relapse remains unclear.MethodsTranscriptome data (GSE3912), and single-cell sequencing data (GSE130116) of B-ALL patients were downloaded from Gene Expression Omnibus (GEO) database. NMRGs were sourced from Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases. Further, the differentially expressed NMRGs (DE-NMRGs) were selected from the analysis between initial diagnosis and relapse B-ALL samples, which further performed functional enrichment analyses. The biomarkers were obtained through random forest (RF) algorithm and repeated cross validation. Additionally, cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm was used to evaluate the immune cell differences between the initial diagnosis and relapse samples, and the correlations between biomarkers and gene markers of differential immune cells were analyzed. Furthermore, single cell RNA sequencing was conducted in the GSE130116 dataset to find key cell clusters. In addition, according to biomarkers expressions, cell clusters were categorized into high and low biomarker expression groups, and Gene Set Enrichment Analysis (GSEA) analysis was performed on them. Finally, the cell clusters with the highest expression of biomarkers were selected to explore the roles of biomarkers in different cell clusters and identify transcription factors (TFs) influencing biological markers.Results23 DE-NMRGs were screened out, which were mainly enriched in nucleoside phosphate metabolic process, nucleotide metabolic process, and Nicotinate and nicotinamide metabolism. Moreover, 3 biomarkers (NADSYN1, SIRT3, and PARP6) were identified from the machine learning. CIBERSORT results demonstrated that four types of immune cells (B Cells naive, Monocyte, Neutrophils, and T cells CD4 memory Activated) were significantly different between the initial diagnosis and the relapse B-ALL samples, and there were strong correlations between biomarkers and differential immune cells such as positive correlation between NADSYN1 and B Cells naive. The single cell analyses showed that the biomarkers were highly expressed in common myeloid progenitors (CMP), granulocyte-macrophage progenitor (GMP), and megakaryocyte-erythroid progenitor (MEP) cell clusters. Gene set enrichment analysis (GSEA) results indicated that 55 GO terms and 3 KEGG pathways were enriched by the genes in high and low biomarker expression groups. It was found that TF CREB3L2(+) was significantly reduced in the high expression group, which may be the TF affecting biomarkers in the high expression group.ConclusionThis study identified NADSYN1, SIRT3, and PARP6 as the biomarkers of B-ALL, explored biological significance of NMRGs in the initial diagnosis and relapse of B-ALL, and revealed mechanism of biomarkers at the level of the single cell.

Azathioprine (AZA) is commonly used for many autoimmune disorders; however, the limitation of its clinical use is due to potential toxicities, including severe leukopenia. Recent studies have identified genetic NUDT15 variants strongly associated with AZA-induced leukopenia in Asian patients. This study aimed to investigate the strength of above genetic association and evaluate the usefulness of prospective screening of the NUDT15 variants to prevent AZA-induced leukopenia in Chinese patients. AZA-induced leukopenia in patients with autoimmune disorders were enrolled from multiple medical centers in Taiwan/China between 2012 and 2017 to determine the strength of genetic association of NUDT15 or TPMT variants by whole exome sequencing (WES). Furthermore, a prospective study was conducted between 2018 and 2021 to investigate the incidence of AZA-induced leukopenia with and without genetic screening. The WES result showed the genetic variants of NUDT15 R139C (rs116855232) (P=3.7 × 10-25 , odds ratio (OR)=21.7, 95% confidence interval (95% CI)=12.1-38.8) and NUDT15 rs746071566 (P=4.2 × 10-9 , OR=7.1, 95% CI=3.7-13.7), but not TPMT, were associated with AZA-induced leukopenia and NUDT15 R139C variant shows the highest sensitivity with 92.5%. Furthermore, the targeted screening of 1,013 participants for NUDT15 R139C enabled those identified as carriers to use alternative immunosuppressants. This strategy resulted in a significant decrease in the incidence of AZA-induced leukopenia compared with historical incidence (incidence rate=from 7.6% decreased to 0.4%; P=9.3 × 10-20 ). In conclusion, the NUDT15 R139C variant was strongly associated with AZA-induced leukopenia in Chinese patients. The genetic screening of NUDT15 R139C followed by use of alternative immunosuppressants in identified carriers effectively decreased the incidence of AZA leukopenia for patients with autoimmune disorders.

The vapor-phase antibacterial activity of essential oils makes them suitable for applications in air disinfection and other fields. At present, vapor-phase antibacterial activity of plant-based essential oils has rarely been reported. Herein, we report a new approach to investigate the antimicrobial activity and mechanism of vapor-phase cinnamaldehyde using Escherichia coli (E. coli) and three other pathogenic bacteria (Pseudomonas aeruginosa, Salmonella, Staphylococcus aureus) as model bacteria. Plate fumigation and agar block transfer techniques were used to determine the antimicrobial activities of vapor-phase cinnamaldehyde fumigation on the four types of bacteria, and the mechanism of action was determined by electrical conductivity (EC), OD260nm measurement, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and fluorescence spectroscopy. Cinnamaldehyde had good vapor-phase antibacterial activity against the four types of bacteria. The TEM, EC, and OD260nm measurements showed that after fumigation with cinnamaldehyde, the ultrastructures of the cells were damaged, and plasmolysis, cell collapse, and leakage of intracellular substances were observed. The FTIR and fluorescence spectroscopy analyses showed that the secondary and tertiary structures of bacterial membrane proteins were altered. These findings indicate that the cell membrane is an important target for plant-based essential oils to exert their vapor-phase antimicrobial effects. The results showed that plant-based essential oils can be developed as volatile broad-spectrum disinfection products and vapor-phase antiseptics.

Funder: Gates Cambridge Trust; Id: http://dx.doi.org/10.13039/501100005370, Parkinson's disease-related proteins, PINK1 and Parkin, act in a common pathway to maintain mitochondrial quality control. While the PINK1-Parkin pathway can promote autophagic mitochondrial turnover (mitophagy) following mitochondrial toxification in cell culture, alternative quality control pathways are suggested. To analyse the mechanisms by which the PINK1-Parkin pathway operates in vivo, we developed methods to detect Ser65-phosphorylated ubiquitin (pS65-Ub) in Drosophila. Exposure to the oxidant paraquat led to robust, Pink1-dependent pS65-Ub production, while pS65-Ub accumulates in unstimulated parkin-null flies, consistent with blocked degradation. Additionally, we show that pS65-Ub specifically accumulates on disrupted mitochondria in vivo. Depletion of the core autophagy proteins Atg1, Atg5 and Atg8a did not cause pS65-Ub accumulation to the same extent as loss of parkin, and overexpression of parkin promoted turnover of both basal and paraquat-induced pS65-Ub in an Atg5-null background. Thus, we have established that pS65-Ub immunodetection can be used to analyse Pink1-Parkin function in vivo as an alternative to reporter constructs. Moreover, our findings suggest that the Pink1-Parkin pathway can promote mitochondrial turnover independently of canonical autophagy in vivo.

Lenvatinib and atezolizumab plus bevacizumab(A + B) have been used for unresectable hepatocellular carcinoma (HCC) as first-line therapy. Real-world studies comparison of efficacy and safety in these two regimens are limited, we therefore conduct this study to investigate these issues.We retrospectively reviewed patients received lenvatinib (n = 46) and A + B (n = 46) as first-line systemic therapy for unresectable HCC in a tertiary medical center. Objective response rate (ORR), progression free survival (PFS), and overall survival (OS) were evaluated according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Inverse probability weighting (IPW) was performed for baseline clinical features balance.A total of 92 patients with median age of 63.8 year-old, 78.3% male, 85.9% viral hepatitis infected, 67.4% BCLC stage C were enrolled. The median treatment and follow-up duration were 4.7 months and 9.4 months, respectively. There was no significant difference in ORR (26.1% vs. 41.3%, p = 0.1226), PFS (5.9 vs. 5.3 months, p = 0.4066), and OS (not reached vs. not reached, p = 0.7128) between the lenvatinib and A + B groups. After IPW, the results of survival and response rate were also compared. Subgroup analysis suggested that using lenvatinib was not inferior to A + B in regards of PFS, including those with elder, Child-Pugh class B, beyond up-to-seven, or portal vein invasion VP4 patients. Among the lenvatinib treated patients, multivariate analysis showed patients elder than 65-year-old was an independent predictor associated with shorter PFS (adjust HR: 2.085[0.914-4.753], p = 0.0213). The incidence rates of adverse events were similar between two groups (76 vs. 63%, p = 0.1740). Both of two regimens had similarly few impact on liver function by comparison of baseline, third month, and sixth month albumin-bilirubin index and Child-Pugh score.The efficacy and safety of lenvatinib are similar to A + B as a first-line systemic therapy for unresectable HCC.

Parkinson's disease (PD) has become the second largest neurodegenerative disease after Alzheimer's disease, and its incidence is increasing year by year. Traditional dopamine replacement therapy and deep brain stimulation can only alleviate the clinical symptoms of patients with PD but cannot cure the disease. In recent years, stem cell therapy has been used to treat neurodegenerative diseases. Many studies have shown that stem cell transplantation has a therapeutic effect on PD. Here, we review recent studies indicating that exosomes derived from mesenchymal stem cells also have the potential to treat PD in animal models, but the exact mechanism remains unclear. This article reviews the mechanisms through which exosomes are involved in intercellular information exchange, promote neuroprotection and freely cross the blood-brain barrier in the treatment of PD. The increase in the incidence of PD and the decline in the quality of life of patients with advanced PD have placed a heavy burden on patients, families and society. Therefore, innovative therapies for PD are urgently needed. Herein, we discuss the mechanisms underlying the effects of exosomes in PD, to provide new insights into the treatment of PD. The main purpose of this article is to explore the therapeutic potential of exosomes derived from mesenchymal stem cells and future research directions for this degenerative disease.