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Graphene oxide (GO) has attracted significant attention as a nano-reinforcement for cement-based materials, owing to its exceptional mechanical properties and abundant surface functional groups. However, the precise mechanisms governing its effects in cement composites remain inadequately understood due to inconsistencies and gaps in the existing literature. This review conducts a comprehensive analysis of the dispersion and reinforcement effects of GO in cement materials, focusing on three key areas: (1) challenges associated with achieving uniform dispersion of GO in the high-pH environment of cement slurries and potential strategies to address them; (2) the influence of GO on the macroscopic properties of cementitious composites, including workability, load-bearing capacity, flexural strength, fracture resistance, and durability; and (3) the reinforcement mechanisms of GO, encompassing its role in hydration kinetics, alterations to the calcium-silicate-hydrate (C-S-H) structure, and bonding interactions at the cement matrix interface. Furthermore, recent advancements in optimizing the dispersion and reinforcement effects of GO, such as surface modification techniques, are explored, emphasizing its potential for multifunctional and intelligent applications. This review aims to provide engineering professionals with the latest insights into the application of graphene oxide as a nano-reinforcement in cement-based composites, while offering valuable guidance and direction for future research in this field.

Introduction: Postoperative pulmonary complications (PPCs) occur frequently in patients undergoing lung surgery under general anaesthesia and are strongly associated with longer postoperative hospital stays and increased mortality. The existing literature has shown that a higher level of preoperative physical activity (PA) plays a positive role in the low incidence of postoperative complications and the quality of life in patients undergoing lung surgery. However, the association between preoperative PA levels and the incidence of PPCs has rarely been studied, particularly in thoracoscopic lung surgery. This study aims to evaluate PA levels in patients undergoing thoracoscopic lung surgery using the International Physical Activity Questionnaire and to investigate the association between PA levels and the incidence of PPCs., Methods and Analysis: A total of 204 participants aged 18-80 years undergoing thoracoscopic lung surgery (thoracoscopic wedge resection, thoracoscopic segmentectomy and thoracoscopic lobectomy) will be included in the study. The primary outcome is the incidence of PPCs within the first 5 postoperative days. The secondary outcomes include the number of PPCs, the incidence of PPCs 1 month postoperatively, the arterial blood levels of inflammatory markers, the incidence of postoperative adverse events within the first 5 postoperative days, extubation time, unplanned admission to the intensive care unit, postoperative length of stay and mortality 1 month postoperatively., Ethics and Dissemination: The study was reviewed and approved by the Research Ethics Committee of the First Affiliated Hospital of Shandong First Medical University on 31 March 2022 (YXLL-KY-2022(014)) and is registered at ClinicalTrials.gov. We plan to disseminate the data and findings of this study in international and peer-reviewed journals., Trial Registration Number: The trial has been prospectively registered at the clinicaltrials.gov registry (NCT05401253)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Interscalene block (ISB) is widely regarded as the gold standard treatment for acute pain following arthroscopic shoulder surgery. However, a single injection of a local anesthetic for ISB may not offer sufficient analgesia. Various adjuvants have been demonstrated to prolong the analgesic duration of the block. Hence, this study aimed to assess the relative efficacy of dexamethasone and dexmedetomidine as adjuncts to prolong the analgesic duration for a single- shot ISB., Methods: The efficacy of adjuvants was compared using a network meta-analysis. The methodological quality of the included studies was evaluated using the Cochrane bias risk assessment tool. A comprehensive search of the PubMed, Cochrane, Web of Science, and Embase databases was conducted with a search deadline of March 1, 2023. Various adjuvant prevention randomized controlled trials have been conducted in patients undergoing interscalene brachial plexus block for shoulder arthroscopic surgery., Results: Twenty-five studies enrolling a total of 2,194 patients reported duration of analgesia. Combined dexmedetomidine and dexamethasone (MD = 22.13, 95% CI 16.67, 27.58), dexamethasone administered perineurally (MD = 9.94, 95% CI 7.71, 12.17), high-dose intravenous dexamethasone (MD = 7.47, 95% CI 4.41, 10.53), dexmedetomidine administered perineurally (MD = 6.82, 95% CI 3.43, 10.20), and low-dose intravenous dexamethasone (MD = 6.72, 95% CI 3.74, 9.70) provided significantly longer analgesic effects compared with the control group., Discussion: The combination of intravenous dexamethasone and dexmedetomidine provided the greatest effect in terms of prolonged analgesia, reduced opioid doses, and lower pain scores. Furthermore, peripheral dexamethasone in prolonging the analgesic duration and lowering opioid usage was better than the other adjuvants when used a single medication. All therapies significantly prolonged the analgesic duration and reduced the opioid dose of a single-shot ISB in shoulder arthroscopy compared with the placebo., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wei, Liu, Lv, Wu, Sun, Gu and Shi.)

Introduction: The aim of this prospective study is to evaluate the effects of combining topical airway anaesthesia with intravenous induction on haemodynamic variables during the induction period in patients undergoing cardiac surgery., Methods and Analysis: This randomised, double-blind, controlled, parallel-group, superiority study from 1 March 2021 to 31 December 2021 will include 96 participants scheduled for cardiac surgery. Participants will be screened into three blocks (ASA II, ASA III, ASA IV) according to the American Society of Anesthesiologists (ASA) grade and then randomly allocated into two groups within the block in a 1:1 ratio. Concealment of allocation will be maintained using opaque, sealed envelopes generated by a nurse according to a computer-generated randomisation schedule. In addition to general intravenous anaesthetics, participants will receive supraglottic and subglottic topical anaesthesia. Changes in arterial blood pressure and heart rate in both groups will be recorded by an independent investigator at the start of anaesthesia induction until the skin incision. If vasopressors are used during this period, the frequency, dosage and types of vasopressors will be recorded. The incidence and severity of participants' postoperative hoarseness and sore throat will also be assessed., Ethics and Dissemination: This study was approved by the Ethics Committee of Qianfoshan Hospital of Shandong Province (registration number: YXLL-KY-2021(003)). The results will be disseminated through a peer-reviewed publication and in conferences or congresses., Trial Registration Number: NCT04744480., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study aimed to elucidate the therapeutic concentration range of phenobarbital (PB) for adults, as well as the influence of therapeutic plasma exchange (TPE) on plasma concentration of PB. We retrospectively reviewed consecutive patients diagnosed with refractory status epileptic (RSE) and treated with a bolus injection of PB as well as TPE, admitted to our neurocritical care unit from November 2015 to October 2016. Continuous electroencephalographic monitoring was performed routinely for these patients. TPE was performed using a continuous-flow cell separator. PB concentrations in the plasma and cerebrospinal fluid were measured by gas chromatography-mass spectrometer analysis before and after TPE. A total of seven patients were included; among these, one patient had RSE related to anti-N-methyl-D-aspartate receptor encephalitis, another patient had Hashimoto encephalopathy, and five patients had undetermined etiology. For patients with clinical and electrographic control (n=6), the plasma concentration of PB ranged from 138 to 243.7 μg/ml. In addition, of six paired plasma samples (before and after TPE) obtained from three patients, no significant differences between the concentrations of PB were detected (P=0.6), suggesting that TPE may not significantly affect the plasma concentration of PB. This study confirmed that PB more than 100 µg/ml was effective for adults with RSE. Moreover, TPE may not have an influence on the plasma concentration of PB.Video abstract: http://links.lww.com/WNR/A489.

A 66-year-old male patient with a 10-year course of Parkinson's disease (PD) was admitted for hallucination lasting a half a month. After treatment with levodopa/carbidopa, selegiline, and piribedil, the patient's motor symptoms were improved while no significant effects were observed on psychotic symptoms. A clinical pharmacist analyzed the pharmacologic and pharmacokinetic characteristics of selegiline and piribedil, summarized the scheme of PD with psychotic symptoms in the literature, and discovered that selegiline might potentiate psychotic side effects of piribedil, while the use of levodopa/carbidopa cannot be ruled out either. Finally, the clinical pharmacist proposed to reduce the dosage of levodopa/carbidopa, increase the dosage of selegiline and quetiapine, and discontinue piribedil. The clinician accepted this suggestion. After the adjustment of medication, the patient's motor symptoms were absolutely improved and the psychotic symptoms were notably improved. This case study suggests that long-term treatment with levodopa/carbidopa and piribedil, along with the progression of the disease itself, could contribute to the emergence of psychotic symptoms in PD. Additionally, selegiline could potentiate psychotic side effects of piribedil. Neurology clinical pharmacists should work alongside neurology clinicians at the bedside to optimize pharmacotherapy, improve patient safety, and contribute to scholarly efforts.

Both the anti- and pro-apoptotic members of the Bcl-2 family are regulated by a conserved Bcl-2 homology (BH3) domain. ABT-263 (Navitoclax), a novel BH3 mimetic and orally bioavailable Bcl-2 family inhibitor with high affinity for Bcl-xL, Bcl-2 and Bcl-w has entered clinical trials for cancer treatment. But the anticancer mechanisms of ABT-263 have not been fully elucidated. In this study we investigated the effects of ABT-263 on human esophageal cancer cells in vitro and to explore its anticancer mechanisms. Treatment with ABT-263 dose-dependently suppressed the viability of 3 human esophageal cancer cells with IC 50 values of 10.7±1.4, 7.1±1.5 and 8.2±1.6 μmol/L, in EC109, HKESC-2 and CaES-17 cells, respectively. ABT-263 (5-20 μmol/L) dose-dependently induced G 1 /G 0 -phase arrest in the 3 cancer cell lines and induced apoptosis evidenced by increased the Annexin V-positive cell population and elevated levels of cleaved caspase 3, cleaved caspase 9 and PARP. We further demonstrated that ABT-263 treatment markedly increased the expression of p21 Waf1/Cip1 and decreased the expression of cyclin D1 and phospho-Rb (retinoblastoma tumor suppressor protein) (Ser780) proteins that contributed to the G 1 /G 0 -phase arrest. Knockdown of p21 Waf1/Cip1 attenuated ABT-263-induced G 1 /G 0 -phase arrest. Moreover, ABT-263 treatment enhanced pro-survival autophagy, shown as the increased LC3-II levels and decreased p62 levels, which counteracted its anticancer activity. Our results suggest that ABT-263 exerts cytostatic and cytotoxic effects on human esophageal cancer cells in vitro and enhances pro-survival autophagy, which counteracts its anticancer activity.

Porous and single-crystalline ZnO nanobelts have been prepared through annealing precursors of ZnSe · 0.5N2H4 well-defined and smooth nanobelts, which have been synthesized via a simple hydrothermal method. The composition and morphology evolutions with the calcination temperatures have been investigated in detail for as-prepared precursor nanobelts, suggesting that they can be easily transformed into ZnO nanobelts by preserving their initial morphology via calcination in air. In contrast, the obtained ZnO nanobelts are densely porous, owing to the thermal decomposition and oxidization of the precursor nanobelts. More importantly, the achieved porous ZnO nanobelts are single-crystalline, different from previously reported ones. Motivated by the intrinsic properties of the porous structure and good electronic transporting ability of single crystals, their gas-sensing performance has been further explored. It is demonstrated that porous ZnO single-crystalline nanobelts exhibit high response and repeatability toward volatile organic compounds, such as ethanol and acetone, with a short response/recovery time. Furthermore, their optoelectronic behaviors indicate that they can be promisingly employed to fabricate photoelectrochemical sensors.

Objective: To explore whether MG-132 could enhance the anti-tumor activity of obatoclax against esophageal cancer cell line CaES-17., Methods: MTT assay was used to determine the cytotoxicity of obatoclax and MG-132 in CaES-17 cells. The IC(50) of obatoclax and MG-132 were used to determine the molar ratio (1:2.4) of the two drugs for combined treatment of the cells. The concentrations of obatoclax and MG-132 ranged from 1/8 IC(50) to 4 IC(50) after serial dilution, and their combination index (CI) was calculated using CompuSyn software. The expression of ubiquitin and the cleavage of PARP, caspase-9, phospho-histone H3 and phospho-aurora A/B/C in the exposed cells were examined with Western blotting; the cell apoptosis was measured by flow cytometry with Annexin V staining, and the percentage of cells in each cell cycle phase was also determined by flow cytometry., Results: The CI of obatoclax and MG-132 was 0.296 for a 50% inhibition of Caes-17 cells and was 0.104 for a 95% inhibition. The cells treated with obatoclax or MG-132 alone showed increased expression of ubiquitin and cleavage of PARP and caspase-9. Compared with the cells treated with obatoclax or MG-132 alone, the cells with a combined treatment exhibited significantly increased expression of ubiquitin, cleavage of PARP and caspase-9, and expression of phospho-Histone H3 (P<0.05). The combined treatment of the cells also resulted in significantly increased expression of phospho-Aurora A/B/C compared with obatoclax treatment alone. The cells with the combined treatment showed significantly higher percentages of apoptotic cells and cells in sub-G(1) and G(2)/M phases compared with the cells treated with either of the drugs (P<0.05)., Conclusion: Obatoclax combined with MG-132 shows a significant synergistic anti-tumor effect against esophageal cancer CaES-17 cells by inducing apoptosis and cell cycle arrest.

Preclinical studies have shown synergism between epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and antifolates in solid tumors. This study is to investigate the efficacy and tolerability of erlotinib plus capecitabine as first-line treatment in older Chinese patients (≥ 65 years) with lung adenocarcinoma. This is an open-label, single arm, multicenter phase II clinical trial. Sixty- two patients with previously untreated stage IIIB/IV adenocarcinoma and age 65 years or above were enrolled at four tertiary teaching hospitals and 2 provincial hospitals in China; 58 patients fulfilled the study requirements. Erlotinib (150 mg/day) and capecitabine (1000 mg/m2 twice daily on days 1-14) were administered during every 21-day cycle. The primary endpoint was the non-progression rate at 12 weeks. EGFR and K-ras mutation rates were determined using PCR. Tumor expression of different biomarkers was assessed using immunohistochemistry. In a cohort of 58 patients, 34 patients had no disease progression at 12 weeks following treatment. The objective response rate was 29.3%, and the disease control rate was 75.9%. The objective response rate was significantly higher in patients with EGFR mutations than in those with wild-type EGFR. Patients with thymidine phosphorylase-negative tumors had significantly longer overall survival after one year than patients with thymidine phosphorylase-positive tumors. Forty-four patients had at least one primary adverse events (AEs), including skin rash (n = 30), grade 3 AEs (n = 17), and grade 4 AEs (n = 7). This is the first phase II clinical trial to assess erlotinib plus capecitabine combination therapy as first-line treatment in older patients with lung adenocarcinoma. Erlotinib/capecitabine chemotherapy was significantly better in patients with EGFR mutations and in those with thymidine phosphorylase-negative tumors. The use of fluorouracil derivatives for the treatment of lung adenocarcinoma warrants further study.

Thirteen new analogues of flavone-8-acetic acid, that is, compounds 10a-m bearing a methoxy group at the 7-position and diverse subsitiuents on the benzene ring at the 2- and 3-positions of flavone nucleus, were synthesized and evaluated for their direct antiproliferative effects on two human tumor cell lines and for their indirect antiproliferative activities in the transwell co-culture system. The results indicated that most of compounds 10a-m showed moderate direct cytotoxicities. Among them, compound 10i exhibited higher direct cytotoxicity and selectivity for both cell lines over BJ human foreskin fibroblast cells than 5,6-dimethylxanthenone-4-acetic acid (DMXAA). Interestingly, compared with DMXAA, compound 10e showed comparable indirect cytotoxicity and higher selectivity. In addition, compound 10e was found to be able to induce tumor necrosis factor α (TNF-α) production in human peripheral blood mononuclear cells., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To study the impact of gonadotropin-releasing hormone analogs (GnRHa) on body mass index (BMI) in girls with idiopathic central precocious puberty (ICPP)., Methods: One hundred and thirty-four girls with ICPP were enrolled. Fifty-seven out of the 134 girls were treated with GnRHa for 1.69±0.43 years. The height, weight, bone age and BMI were measured before treatment, at the end of the treatment and after reaching near adult height and compared with those in the untreated 77 girls., Results: The adult predicted height standard deviation score (SDS) at the end of treatment was significantly higher than that before treatment (P<0.01) and was similar to the target height SDS in the GnRHa treatment group (P>0.05). With GnRHa treatment, the near-adult height SDS was higher than the target height SDS (P<0.01). At the end of treatment, the BMI SDS slightly increased compared with pretreatment level (P>0.05). A significant reduction in the BMI was observed when reaching the near-adult height in the GnRHa treatment group compared to the level of pretreatment and the untreated group (P<0.01). However, the BMI in the GnRHa treatment group before treatment, at the end of the treatment and after reaching near adult height remained in the normal range (±1 SD)., Conclusions: GnRHa may improve the final height in girls with ICPP. The alterations of BMI after GnRHa therapy fluctuate in a normal range.

Objective: To investigate the mechanism of the development of cisplatin resistance in a human esophageal squamous carcinoma cell line., Methods: The cytotoxicity of cisplatin in the cisplatin-resistant resistant cell line EC109/CDDP and its parental cell line EC109 was measured by MTT assay. Whole-cell cisplatin accumulation and Pt-DNA adduct formation were determined by inductively coupled plasma mass spectrometry (ICP-MS). Western blotting was used to investigate the protein expression of full length PARP, cleaved PARP, and copper transporter 1 (CTR1)., Results: EC109/CDDP cells was more resistant to cisplatin-induced cytotoxicity and apoptosis than EC109 cells. Compared with EC109 cells, EC109/CDDP cells exhibited less cisplatin accumulation and Pt-DNA adduct formation with also decreased CTR1 protein expression., Conclusion: Cisplatin induces drug resistant phenotype by decreasing the protein level of CTR1, which controls cell accumulation and cytotoxic effect of cisplatin.

A series of benzofuropyrazoles 2a-i were synthesized in 10-92% from the reaction of 2-aroylbenzofuran-3-ols 1a-i with hydrazine hydrate, and screened for their antitumor activities toward four human solid tumor cell lines, including gastric carcinoma cells MKN45, hepatocellular carcinoma cells HepG2, breast cancer cells MCF-7, and lung cancer cells A549. The results indicated that both compounds 1a-i and 2a-i displayed moderate antitumor activities. Among them, compound 2e exhibited potent inhibitory activity toward all the four tumor cell lines. In addition, compounds 1e and 2e showed strong DNA-binding affinities, and induced an increase in the viscosity of calf-thymus DNA, suggesting that they might act as an intercalator.

Objective: To explore a chemotherapeutic regimen suitable for non-small cell lung cancer (NSCLC) in elderly patients., Methods: A total of 68 elderly patients with NSCLC (stage IIIb/IV) were equally and randomly divided into single-agent and combined groups. Patients in single-agent group received gemcitabine 1000 mg/m(2) at Days 1 and 8 for a 21-day cycle. Those in combined group received gemcitabine 1000 mg/m(2) at Days 1 and 8 in combination carboplatin AUC5 at Day 2 for a 21-day cycle. The drugs were intravenously administered. All patients received 3 cycles of treatment., Results: In single-agent and combined groups, CR 1 and 1, PR 12 and 13, response rates 38% and 41% were respectively observed. There was no statistically significant difference between two groups (P > 0.05). The 1-year and 2-year survival rates of single-agent and combined groups were 31% vs 32% and 12% vs 14% with a median survival of 9.9 and 9.8 months without a statistically significant difference (P > 0.05). The rates of leucopenia and thrombocytopenia (III-IV degree) were 47% and 38% in combined group and they were higher than 24% and 15% in single-agent group with a statistically significant difference (P < 0.05). The observer scale of lung cancer symptom scale showed that the post-treatment scores of appetite, fatigue and pain significantly improved in single-agent group while no improvement was observed in combined group. Also the scores of appetite, fatigue and pain of single-agent group were higher than those of combined group after chemotherapy (P < 0.05)., Conclusion: Single-agent gemcitabine regimen is more suitable for advanced NSCLC in elderly patients.

Objective: To investigate the resistance of Helicobacter pylori (H. pylori) to antimicrobial agents in adolescents., Methods: One hundred and eight adolescents (6-18 years old) underwent a gastroscopy examination. H. pylori strains were isolated from gastric mucosa. Antimicrobial susceptibility testing was performed by means of Kirby-Baner., Results: Thirty-six H. pylori strains were identified. The resistant rate of H. pylori strains to clarithromycin, fruranzolidone and amoxicillin was 8.3%, 16.7% and 33.3%, respectively. H. pylori strains showed a high resistance to metronidazole (94.4%), while no strain was resistant to gentamicin and levofloxacin., Conclusions: The H. pylori strains from the adolescents in Zhejiang showed a high resistance to metronidazole and amoxicillin but a low resistance to clarithromycin and fruranzolidone. All of H. pylori strains were susceptive to gentamicin and levofloxacin.