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Bo Li,1,2 Li Jiang,1,2 Ni Wu,1,2 Yao Chen,1,2 Zhi Xu,3 Fengcheng Xu,2,4 Heping Chen,1 Tianhu Liu2,4 1Clinical Pharmacy Department, The Third Affiliated Hospital of Chengdu Medical College, Pidu District People’s Hospital, Chengdu, Sichuan, People’s Republic of China; 2Drug Clinical Trial Management Center, The Third Affiliated Hospital of Chengdu Medical College, Pidu District People’s Hospital, Chengdu, Sichuan, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The Third Affiliated Hospital of Chengdu Medical College, Pidu District People’s Hospital, Chengdu, Sichuan, People’s Republic of China; 4Department of Cardiovascular Medicine, The Third Affiliated Hospital of Chengdu Medical College, Pidu District People’s Hospital, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Bo Li, Clinical Pharmacy Department, The Third Affiliated Hospital of Chengdu Medical College, Pidu District People’s Hospital, Chengdu, Sichuan, People’s Republic of China, Email lbydcg@163.com Tianhu Liu, Department of Cardiovascular Medicine, The Third Affiliated Hospital of Chengdu Medical College, Pidu District People’s Hospital, Chengdu, Sichuan, People’s Republic of China, Email lthzgl@163.comBackground: In 2021, National Health Commission of the People’s Republic of Chinese issued a document that no longer recommended the routine skin test for cephalosporin (RSTC). However, there is still resistance to the cancellation of RSTC in a primary hospital. The study aimed to explore the potential factors for hindering the abolition of the RSTC in a county-level hospital based on the PRECEDE model.Methods: The cross-sectional study was conducted on healthcare workers in the Pidu District People’s Hospital, Chengdu, by online questionnaire from September 10 to September 25 in the 2021.The PRECEDE model was used to divide the potential factors of healthcare professionals in hindering the abolition of the RSTC into predisposing factors, enabling factors and reinforcing factors. Data were analyzed by ANOVA, Chi-square test, multiple linear and multiple logistic regression analysis.Results: We collected 605 respondents’ valid questionnaires. 254 healthcare professionals were against cancellation of the RSTC, accounting for 41.98%. Multiple linear regression analysis showed that working for 6~10 years (β = 1.953, P = 0.024), medium (β = 1.995, P = 0.030) or senior (β = 4.003, P = 0.007) professional qualification, pharmacists (β = 3.830, P = 0.013) and working in surgical department (β= 4.462, P < 0.001) were significantly associated with higher score of predisposing factors, enabling factors, and reinforcing factors on abolition of RSTC. Furthermore, multiple logistic regression analysis showed that pharmacists (OR=3.113, 95% CI: 1.341– 7.223, P=0.030), medium professional qualification (OR=1.272, 95% CI: 0.702– 2.302, P=0.008), scores of predisposing factors (OR=1.335, 95% CI: 1.033– 1.726, P=0.009), and scores of enabling factors (OR=1.208, 95% CI: 1.109– 1.315, P< 0.001) were independently associated with the positive anticipated behavior on the abolition of RSTC. While nurses (OR=0.516, 95% CI: 0.284– 0.938, P< 0.001) were independently associated with anticipated negative behavior.Conclusion: Pharmacists, medium professional qualification, and healthcare professionals with higher scores of predisposing and enabling factors were more likely to have a positive anticipated behavior on the abolition of RSTC, while nurses did not.Keywords: cephalosporin, skin test, potential factors, PRECEDE model, cross-sectional study

A new species Veronica hongii, from western Hubei Province, Central China is described and illustrated. The species is morphologically similar to V. henryi Yamazaki, but mainly differs in the glabrous plant, except pedicels, broadly ovate leaf blades, glandular-pubescent pedicels, obovate calyx lobes, smaller corolla, broadly ovate capsule and much smaller seeds.

Bipolar plates are a key part of fuel cells. The optimal hot press temperature, pressure, and time were determined in this study. The press condition can directly affect the relative density, thereby improving the conductivity and mechanical property. Several carbon black doped samples were also successfully prepared on the basis of the optimized preparation method. Results show that carbon black optimized the conductivity due to the “conduction bridge”. The maximum conductivity and bending strength reached 345 S/cm and 32.5 MPa, respectively. Key words: fuel cells; bipolar plate; graphite; composite materials.

Background: Alzheimer’s disease (AD) is the most common form of neurodegenerative dementia among the elderly. Excitotoxicity has been implicated as playing a dominant role in AD, especially related to the hyperactivation of excitatory neurons. Death-associated protein kinase 1 (DAPK1) is a calcium/calmodulin-dependent kinase and involved in the pathogenesis of AD, but the roles and mechanisms of DAPK1 in excitotoxicity in AD are still uncertain. Objective: We mainly explored the underlying mechanisms of DAPK1 involved in the excitotoxicity of AD and its clinical relevance. Methods: Differentiated SH-SY5Y human neuroblastoma cells, PS1 V97 L transgenic mice, and human plasma samples were used. Protein expression was assayed by immunoblotting, and intracellular calcium and neuronal damage were analyzed by flow cytometry. Plasma DAPK1 was measured by ELISA. Results: We found that DAPK1 was activated after amyloid-β oligomers (AβOs) exposure in differentiated SH-SY5Y cells. Besides, we found the phosphorylation of GluN2B subunit at Ser1303 was increased, which contributing to excitotoxicity and Ca2+ overload in SH-SY5Y cells. Inhibiting DAPK1 activity, knockdown of DAPK1 expression, and antagonizing GluN2B subunits could effectively prevent AβOs-induced activation of GluN2B subunit, Ca2+ overload, and neuronal apoptosis. Additionally, we found that DAPK1 was elevated in the brain of AD transgenic mouse and in the plasma of AD patients. Conclusion: Our finding will help to understand the mechanism of DAPK1 in the excitotoxicity in AD and provide a reference for the diagnosis and therapy of AD.

A skin wound represents a rupture caused by external damage or the existence of underlying pathological conditions. Sometimes, skin wound healing processes may place a heavy burden on patients, families, and society. Wound healing processes mainly consist of several continuous, dynamic, but overlapping stages, namely, the coagulation stage, inflammation stage, proliferation stage, and remodeling stage. Bacterial infection, excessive inflammation, impaired angiogenesis, and scar formation constitute the four significant factors impeding the recovery efficacy of skin wounds. This encourages scientists to develop multifunctional nanomedicines to meet challenging needs. As we know, mesenchymal stem cells (MSCs) have been widely explored for wound repair owing to their unique capability for self-renewal and multipotency. However, problems including immune concerns and legal restrictions should be properly resolved before MSC-based therapeutics are safely and widely used in clinics. Besides, maintaining the high viability/proliferation capability of MSCs during administration processes and therapy procedures is also one of the biggest technical bottlenecks. Extracellular vesicles (EVs) are cell-derived nanovesicles, that not only possess the basic characteristics and functions of their corresponding maternal cells but also contain several outstanding advantages including abundant sources, excellent biocompatibility, and convenient administration routes. Furthermore, the membrane surface and cavity are easy to flexibly modify to meet versatile application needs. Recently, MSC-derived EVs have emerged as promising therapeutics for skin wound repair. However, current reviews are too broad and rarely focused on the specific roles of EVs in the different stages of wound recovery. Therefore, it is quite necessary to demonstrate the significance of stem cell-derived EVs in promoting wound healing from several specific aspects. Here, this review primarily tries to provide critical comments on current advances in EVs derived from MSCs for wound repair, particularly elaborating on their impressive roles in effectively eliminating infections, inhibiting inflammation, promoting angiogenesis, and reducing scar formation. Last but not least, current limitations and future prospects of EVs derived from MSCs in the areas of wound repair are also objectively analyzed.

Ar-calcined NCS-CoPt shows a robust HER activity owing to its highly active CoPt3 sites and pyridinic N enriched carbon nanosheets.

Organic–inorganic halide perovskites (OIHPs) are very eye-catching due to their chemical tunability and rich physical properties such as ferroelectricity, magnetism, photovoltaic properties and photoluminescence.

A new ferroelastic organic salt nicotinic acid bromide (N–Br) with high Tc, reversible ferroelastic transition and white light was obtained by halogen substitution.

We carried out the polarimetric observation of the white-light inner corona during the 2017 total solar eclipse in the United States. Degree of linear polarization (DLP) of the inner corona is obtained by the modulated polarized data. The electron density is inferred from the normalized white-light polarization brightness data. According to the observational results, we find that: (1) The DLP of the white-light corona increases with the height, peaking at approximately $1.3 \sim 1.35\, {\rm R}_{\odot }$ and then slightly decreases. In the coronal streamer region, DLP peaks at approximately 1.35 R⊙ and its value is about 40 per cent, whereas in the coronal hole region, DLP peaks at approximately 1.3 R⊙ and its value is about 35 per cent. (2) The azimuth angle of polarization sin (2χ) is symmetrical around the solar disk center. It can be easily found that the gradients of the angle of polarization, representing the direction of oscillations of the electric vector E, are tangential. Above the active region, the DLP distribution changes significantly, whereas the azimuth distribution is stable. This proves that the polarization of white-light corona is mainly caused by scattering polarization. (3) The electron density and the K-corona have similar distributions of properties. Electron density decreases from 6 × 107cm−3 to 2 × 106cm−3, whereas the height increases from $1.1\, {\rm R}_{\odot }$ to $1.85\, {\rm R}_{\odot }$. (4) An interesting finding is that, in the cavity region, there may be other polarization-induced mechanisms besides scattering, which can affect the value of the white-light DLP.

Rational design of low-cost and efficient electrocatalyst for the anodic oxygen evolution reaction (OER) to replace noble-metal-based catalysts is greatly desired for the large-scale application of water electrocatalysis. And compared with the conventional powdery catalysts, the freestanding electrode architecture is more attractive owing to the enhanced kinetics and stability. In this work, we report an electrospinning-carbonization-post oxidation strategy to develop the freestanding N-doped carbon nanofibers anchored with Ni/NiO nanoparticles (denoted as Ni/NiO-NCNFs) as efficient OER electrocatalyst. In the synthesized Ni/NiO-NCNFs, the conductive ultrathin carbon layer could promote electron transfer and thus improve the electrocatalytic activity. Meanwhile, the ratio between Ni and NiO could be regulated by tuning the oxidation duration, so as to optimize the adsorption energy of intermediates and improve the OER activity. The Ni/NiO-NCNFs prepared with the oxidation time of 3 h exhibit a promising OER activity and long-term operation durability in 0.1 M KOH solution, requiring an overpotential as small as 153 mV to achieve a current density of 10 mA cm

This research aimed to observe the clinical effects of iRoot-BP along with collagen sponge applied in apical barrier surgery. 46 immature teeth were divided into traumatic group (n =25) and non-traumatic group (n =21) according to the etiology of necrotic pulps. While depending on whether collagen sponges are used during the apical barrier surgery, the 46 teeth were randomly divided into non-collagen group (n = 23) and collagen group (n = 23). Patients were scheduled for follow-up during 12 months to undergo clinical and radiological examination. The etiological analysis showed that the failure of both groups were caused by trauma, which indicated that there might be a negative correlation between trauma and success rate of periapical tissue healed (χ2 = 2.696, P = 0.10). Healing results of apical lesions indicated that 22 affected teeth in collagen group and 21 affected teeth in non-collagen healed well, without clinical and imaging manifestations of failure (χ2 = 0.357, P = 0.55). Assessment results of root sustainable growth suggested that the incomplete tooth roots in collagen group had different degrees of growth, with an average increase of about 2 mm (P

Neuronal death and synaptic loss are principal pathological features of Alzheimer's disease (AD). Amyloid beta oligomers (AβOs) constitute the main neurotoxin underscoring AD pathology. AβOs interact with N-methyl-D-aspartate receptors (NMDARs), resulting in neurotoxic events, including activation of apoptosis and synaptic impairment. Carnosic acid (CA), extracted from Salvia rosmarinus, has been verified its neuroprotective effects in AD. However, the precise mechanisms by which CA induces synaptic protection remain unclear. In this study, we established an in vitro AD model using SH-SY5Y human neuroblastoma cells. We observed that CA improved neuronal survival by suppressing apoptosis. Moreover, CA restored synaptic impairments by increasing expression levels of brain-derived neurotrophic factor (BDNF), postsynaptic density protein-95 (PSD-95), and synaptophysin (Syn). Furthermore, we found these protective effects were dependent on inhibiting the phosphorylation of NMDAR subtype 2B (NMDAR2B), which further suppressed calcium overload and promoted activation of the extracellular signal-regulated kinase (ERK)-cAMP response element-binding protein (CREB) pathway. Administration of N-methyl-D-aspartic acid (NMDA), an agonist of NMDARs, abolished these effects of CA. Our findings demonstrate that CA exerts neuroprotective effects in an in vitro model of AD by regulating NMDAR2B and its downstream cascades, highlighting the therapeutic potential of CA as a NMDARs-targeted candidate in the treatment of AD.

A decision-making method with double reference points was built to address the multiattribute group decision-making (MAGDM) problem to better reflect the influences of bottom-line and target on group decision-making behaviors. First, the relationship between double reference points and attitude characteristics of decision-makers was analyzed, and the rules of use of linguistic variables were disclosed. Second, the loss and utility functions were given according to relations between the reference points and gain/loss values. Third, the weights of attributes were determined with references to the variation coefficient method. Later, alternatives were classified according to risk probability, and ranking and selection of alternatives were carried out through utility information aggregation. Finally, the new method was applied to solve the technological innovation environmental assessment problem. Research results demonstrate that the new method can classify alternatives according to feasibility. The rank of feasible alternatives of the new method is consistent with that of the traditional method. Research conclusions further enrich the research scope of multiattribute decision-making problems and provide some references to study MAGDM problems.

Liver metastasis commonly occurs; however, the luminal-type liver metastasis rarely develops at the early stage of breast cancer, posing key challenges in screening patients, giving early targeted treatment, and providing an opportunity to prolong survival. A 44-year-old female was diagnosed with breast cancer (pT2N0M0, IIa) and luminal B type postoperatively. The latest guidelines indicated four cycles of albumin-paclitaxel and cyclophosphamide chemotherapy. After 4 months of treatment, the patient was found to have hypoechoic nodules in the liver due to other diseases and was thereby diagnosed with breast cancer with liver metastasis. The latest guidelines did not recommend routine imaging and hematological examination of asymptomatic early breast cancer during follow-up. We suggest that follow-up should be strengthened for high-risk patients to maximize their benefits from early diagnosis and treatment.

PURPOSE Aumolertinib (formerly almonertinib; HS-10296) is a novel third-generation epidermal growth factor receptor tyrosine kinase inhibitor approved in China. This double-blind phase III trial evaluated the efficacy and safety of aumolertinib compared with gefitinib as a first-line treatment for locally advanced or metastatic EGFR-mutated non–small-cell lung cancer (NSCLC; ClinicalTrials.gov identifier: NCT03849768 ). METHODS Patients at 53 sites in China were randomly assigned 1:1 to receive either aumolertinib (110 mg) or gefitinib (250 mg) once daily. The primary end point was progression-free survival (PFS) per investigator assessment. RESULTS A total of 429 patients who were naïve to treatment for locally advanced or metastatic NSCLC were enrolled. PFS was significantly longer with aumolertinib compared with gefitinib (hazard ratio, 0.46; 95% CI, 0.36 to 0.60; P < .0001). The median PFS with aumolertinib was 19.3 months (95% CI, 17.8 to 20.8) versus 9.9 months with gefitinib (95% CI, 8.3 to 12.6). Objective response rate and disease control rate were similar in the aumolertinib and gefitinib groups (objective response rate, 73.8% and 72.1%, respectively; disease control rate, 93.0% and 96.7%, respectively). The median duration of response was 18.1 months (95% CI, 15.2 to not applicable) with aumolertinib versus 8.3 months (95% CI, 6.9 to 11.1) with gefitinib. Adverse events of grade ≥ 3 severity (any cause) were observed in 36.4% and 35.8% of patients in the aumolertinib and gefitinib groups, respectively. Rash and diarrhea (any grade) were observed in 23.4% and 16.4% of patients who received aumolertinib compared with 41.4% and 35.8% of those who received gefitinib, respectively. CONCLUSION Aumolertinib is a well-tolerated third-generation epidermal growth factor receptor tyrosine kinase inhibitor that could serve as a treatment option for EGFR-mutant NSCLC in the first-line setting.

The zeolitic imidazolate frameworks (ZIFs) with three-dimensional periodic micropores encounter the barrier of the mass transfer in the diffusion-limited processes. To solve this question, the zeol...

We describe a stereocontrolled synthesis of 3, the fully glycosylated monomeric unit of the dimeric cytotoxic bacterial metabolite (−)-lomaiviticin A (2). A novel strategy involving convergent, site- and stereoselective coupling of the β,γ-unsaturated ketone 6 and the naphthyl bromide 7 (92%, 15:1 diastereomeric ratio (dr)), followed by radical-based annulation and silyl ether cleavage, provided the tetracycle 5 (57% overall), which contains the carbon skeleton of the aglycon of 3. The β-linked 2,4,6-trideoxy-4-aminoglycoside l-pyrrolosamine was installed in 73% yield and with 15:1 β:α selectivity using a modified Koenigs–Knorr glycosylation. The diazo substituent was introduced via direct diazo transfer to an electron-rich benzoindene (4 → 27). The α-linked 2,6-dideoxyglycoside l-oleandrose was introduced by gold-catalyzed activation of an o-alkynyl glycosylbenzoate (75%, >20:1 α:β selectivity). A carefully orchestrated endgame sequence then provided efficient access to 3. Cell viability studies indicated that monomer 3 is not cytotoxic at concentrations up to 1 μM, providing conclusive evidence that the dimeric structure of (−)-lomaiviticin A (2) is required for cytotoxic effects. The preparation of 3 provides a foundation to complete the synthesis of (−)-lomaiviticin A (2) itself.

Benzenesulfonamide compounds containing piperazine heterocycles have prospective pharmacological activity. Two benzenesulfonamide compounds were synthesized. Based on density functional theory (DFT), the optimized structures of the two molecules were calculated using the B3LYP method. DFT was also used for further study of the molecular electrostatic potential and leading molecular orbital. Single crystal of 1-ethyl-4-(phenylsulfonyl)piperazine was studied. The intermolecular interaction and contact were quantified using Hirshfeld surface analysis and 2D fingerprint plots. Conformational analysis showed that the molecular structure after DFT optimization was consistent with the crystal structure determined by x-ray single crystal diffraction.

The present study aimed to equate the 9-item Patient Health Questionnaire (PHQ-9) and 7-item Generalized Anxiety Disorder Scale (GAD-7) to the Hospital Anxiety and Depression Scale (HADS) depression and anxiety subscales (HADS-D,HADS-A) respectively in patients with major depressive disorder (MDD) and generate crosswalks of raw scores.As it is a single group design that adopts common-person equating method, a total of 460 patients with MDD completed the PHQ-9, GAD-7 and HADS at the same time. Rasch analysis was used to filter out invalid participants, investigate the psychometric properties of test items and participants, link the PHQ-9 and HADS-D as well as GAD-7 and HADS-A, and produce conversion tables respectively. The differences between original scores and converted scores were analyzed to validate the crosswalks.401 samples of depression part and 396 samples of anxiety part were left for final samples. Both the PHQ-9 / HADS-D and GAD-7 / HADS-A combined analysis adequately fit the unidimensional Rasch model, demonstrated acceptable reliability and item-person targeting and showed no disordering category. Slight differential item functioning across gender was found in item PHQ9 and item GAD6. The crosswalks were generated and verified to be validity.The results might be restricted to patients with MDD recruited in a single mental health center.The PHQ-9, GAD-7 and HADS depression and anxiety subscales were successfully linked, producing conversion tables that could be used for directly converting raw score from one instrument to the other.

Stick-slip actuators are in high demand in both scientific research and industrial applications. However, backward motion in stick-slip actuators has greatly limited further development. Therefore, to suppress the backward motion, a new flexible beam actuator is proposed in this paper. Correspondingly, a flexible beam actuator is designed to investigate whether the flexible beam can suppress the backward motion. Firstly, a driving mechanism is designed by employing the finite element and pseudo-rigid body methods. Secondly, experiments are conducted on the actuator. The results demonstrate that the actuator can achieve three different displacement curves at different driving voltages: backward motion, smooth motion, and sudden jump. The contact force of the actuator, which has the highest load capacity of 3.9 N, can be adjusted according to the initial load. The actuator achieved 23.714 mm/s at 400 Hz. Additionally, the dynamics model of the actuator is established for investigating the dynamic characteristics of the actuator. Based on the obtained results, the feasibility of suppressing backward motion by a flexible beam is confirmed in this paper, which will further broaden the scope of the application.

Bilateral hepatolithiasis is an intractable disease and repeated attacks of acute cholangitis seriously threaten patient health. The surgical approaches evolve along with gradually greater understanding of its pathophysiology.This is a retrospective cohort study for bilateral hepatolithiasis from January 1958 to December 2018. Before May 1993 (Group A, n = 70), three surgical approaches were adopted: 37 patients with common bile duct exploration (CBDE), 29 with choledochoenterostomy (CE) and four with partial hepatectomy (PH). After June 1993 (Group B, n = 150), 101 patients underwent Oddi sphincter-preserved cholangioplasty with hepatico-subcutaneous stoma (OSPCHS), and 16 with CBDE, 21 with CE, 12 with PH. The perioperative and long-term outcomes were compared.After 1993, the cholangitis recurrence rate significantly decreased from 49.2% to 20.9%, and the stone recurrence rate from 76.3% to 37.1% (both P .001). Also, the stone-/cholangitis-free durations were prolonged significantly (median: 50.8 vs 26.4/49.6 vs 16.2 months, both P .001). Preoperative cholangitis was an independent risk factor for stone recurrence (hazard ratio [HR] = 1.863, P = .018), and residual stone for cholangitis recurrence (HR = 2.838, P .001). OSPCHS and PH were protective surgical approaches for recurrent stone (CBDE: reference; OSPCHS: HR = .469, P = .016, PH: HR = .219, P = .018) and cholangitis (CBDE: reference; OSPCHS: HR = .421, P = .010, PH: HR = .283, P = .093).For bilateral hepatolithiasis, the management should focus on hepatobiliary lesion eradication and Oddi sphincter function preservation.

In this study, 1-(2-bromo-4-(dimethylamino)phenyl)-4-(2-chlorobenzyl)-[1,2,4] triazolo[4,3-a]quinazolin-5(4H)-one was synthesized via a five-step reaction and its single-crystal was obtained via solution crystallization, which was followed by crystallographic analysis. The molecular structure was calculated using density functional theory (DFT) and conformational analysis showed that the optimized molecular structure from DFT was comparable with that elucidated using X-ray diffraction. At the same time, the physicochemical properties of the compound could be understood by analyzing its frontier molecular orbitals and molecular electrostatic potentials.

There are many studies and reviews of the relationship between the asthma disease in young individuals on the one hand and caries and dental erosion on the other. The causes of caries and dental erosion might be related to the asthmatic drugs, low pH and the sweeteners that the inhaled drug contains and perhaps even the lifestyle of children and adolescents with asthma. The main focus of this review is therefore to describe various preventive strategies, based on long experience of preventive dental care in Sweden. Two fact boxes are presented, one on fluoride toothpaste as a population-based intervention for different ages and one on diet counselling in children and adolescents with asthma. The most important thing is to introduce fluoride toothpaste early in the child's life and that the parents brush the child's teeth twice a day, in the morning after breakfast and at night before bedtime, up to the age of 10. Moreover, a high-risk approach with an additional fluoride supply at home is presented, together with the application of fluoride varnish at the clinic. Regarding diet counselling, it is important to make sure that the child has regular meals during the day, maximum five to six times a day, to allow the teeth to rest between meals and restrict sweets and soft drinks to once a week. It is important to identify children and adolescents with asthma as early as possible and to refer them to a dental team for preventive treatment.