Craniocervical posture in patients with skeletal malocclusion and its correlation with craniofacial morphology during different growth periods.

The association between craniocervical posture and craniofacial structures in the various sagittal skeletal malocclusion during different growth stages has been the focus of intense interest in fields of orthodontics, but it has not been conclusively demonstrated. Thus, this study aimed to investigate the association between craniofacial morphology and craniocervical posture in patients with sagittal skeletal malocclusion during different growth periods. A total of 150 from a large pool of cephalograms qualified for the inclusion and exclusion were evaluated and classified into three groups according to the Cervical Vertebral Maturation (CVM) by examining the morphological modifications of the second through fourth cervical vertebrae, each group consisted of 50 cephalograms. In each growth period, for the comparison of head and cervical posture differences among various skeletal classes, the radiographs were further subdivided into skeletal Class I (0° < ANB < 5°, n = 16), skeletal Class II (ANB ≥ 5°, n = 18), and skeletal Class III (0° ≤ ANB, n = 16) on the basis of their ANB angle. There was no significant difference in gender (P > 0.05). Some variables were found to be significant during pubertal growth and later in patients with sagittal skeletal malocclusion (P < 0.05). Most indicators describing craniocervical posture were largest in skeletal Class II and smallest in skeletal Class III during the peak growth periods and later. Cervical inclination variables were greater in skeletal Class III than in skeletal Class II. Variables of craniofacial morphology and craniocervical posture are more correlated during the pubertal growth period and later in patients with sagittal skeletal malocclusion. A tendency is an indication of the close interrelationship that a more extended head was in skeletal Class II while a flexed head was in skeletal Class III. Nevertheless, with the considerations of some limitations involved in this study, further longitudinal studies with large samples are required to elucidate the relationship clearly.

Claudin18.2 expression and its clinicopathological feature in adenocarcinoma from various parts.

AIMS: To clarify claudin18.2 expression and its clinicopathological features in various cancers, especially in lung adenocarcinoma. METHODS: Immunohistochemistry staining and fluorescence in situ hybridisation (FISH) were performed to detect claudin18.2 expression and CLDN18 gene rearrangement in adenocarcinoma from different organs. RESULTS: The results showed that claudin18.2 expression was found in 68% (27 of 40) of lung mucinous adenocarcinoma, 52% (16 of 31) of cholangiocarcinoma, 2% (10 of 423) of colorectal adenocarcinoma tissue microarray, 27% (6 of 22) of colorectal mucinous adenocarcinoma and 30% (3 of 10) of cervical adenocarcinoma, but not in all 39 cases of invasive breast adenocarcinoma by immunohistochemistry staining. There was significantly positive correlation between ratio of claudin18.2-positive carcinoma cells and staining intensity in lung mucinous adenocarcinoma and cholangiocarcinoma. Claudin18.2 expression was much more in female patients than male patients with lung mucinous adenocarcinoma. In addition, cholangiocarcinoma with claudin18.2 expression was more aggressive and had perineural invasion. Intraductal papillary neoplasm of the bile duct and epithelial dysplasia of the adjacent bile in cholangiocarcinoma also showed claudin18.2 expression. All three cases of cervical adenocarcinoma with claudin18.2 expression were moderately differentiated adenocarcinoma including one human papillomavirus (HPV)-associated carcinoma, two non-HPV-associated and gastric-type carcinoma. CLDN18 gene rearrangement was not found in all 22 cases with high claudin18.2 expression by FISH. CONCLUSIONS: Our results suggest claudin18.2 might be a potential biomarker for targeted therapy on lung mucinous adenocarcinoma, cholangiocarcinoma, colorectal mucinous adenocarcinoma and gastric-type cervical adenocarcinoma.

Integrated analyses revealed the potential role and immune link of mitochondrial dysfunction between periodontitis and type 2 diabetes mellitus.

There is a reciprocal comorbid relationship between periodontitis and type 2 diabetes mellitus (T2DM). Recent studies have suggested that mitochondrial dysfunction (MD) could be the key driver underlying this comorbidity. The aim of this study is to provide novel understandings into the potential molecular mechanisms between MD and the comorbidity, and identify potential therapeutic targets for personalized clinical management. MD-related differentially expressed genes (MDDEGs) were identified. Enrichment analyses and PPI network analysis were then conducted. Six algorithms were used to explore the hub MDDEGs, and these were validated by ROC analysis and qRT-PCR. Co-expression and potential drug targeting analyses were then performed. Potential biomarkers were identified using LASSO regression. The immunocyte infiltration levels in periodontitis and T2DM were evaluated via CIBERSORTx and validated in mouse models. Subsequently, MD-related immune-related genes (MDIRGs) were screened by WGCNA. The in vitro experiment verified that MD was closely associated with this comorbidity. GO and KEGG analyses demonstrated that the connection between periodontitis and T2DM was mainly enriched in immuno-inflammatory pathways. In total, 116 MDDEGs, eight hub MDDEGs, and two biomarkers were identified. qRT-PCR revealed a distinct hub MDDEG expression pattern in the comorbidity group. Altered immunocytes in disease samples were identified, and their correlations were explored. The in vivo examination revealed higher infiltration levels of inflammatory immunocytes. The findings of this study provide insight into the mechanism underlying the gene-mitochondria-immunocyte network and provide a novel reference for future research into the function of mitochondria in periodontitis and T2DM.

Sodium sulfite-driven Helicobacter pylori eradication: Unraveling oxygen dynamics through multi-omics investigation.

Due to the emergence and spread of multidrug resistance in Helicobacter pylori (H. pylori), its eradication has become difficult. Sodium sulfite (SS), a widely used food additive for ensuring food safety and storage, has been recognized as an effective nonbactericidal agent for H. pylori eradication. However, the mechanism by which H. pylori adapts and eventually succumbs under low- or no-oxygen conditions remains unknown. In this study, we aimed to evaluate the anti-H. pylori effect of SS and investigated the multiomics mechanism by which SS kills H. pylori. The results demonstrated that SS effectively eradicated H. pylori both in vitro and in vivo. H. pylori responds to the oxygen changes regulated by SS, downregulates the HcpE gene, which is responsible for redox homeostasis in bacteria, decreases the activities of enzymes related to oxidative stress, and disrupts the outer membrane structure, increasing susceptibility to oxidative stress. Furthermore, SS downregulates the content of cytochrome C in the microaerobic respiratory chain, leading to a sharp decrease in ATP synthesis. Consequently, the accumulation of triglycerides (TGs) in bacteria due to oxidative stress supports anaerobic respiration, meeting their energy requirements. The multifaceted death of H. pylori caused by SS does not result in drug resistance. Thus, screening of the redox homeostasis of HcpE as a new target for H. pylori infection treatment could lead to the development of a novel approach for H. pylori eradication therapy.

Anticancer effect of covalent purine-containing EGFR TKI, ZZC4 and its mechanism of action through network pharmacology.

AIMS: Epidermal growth factor receptor (EGFR) has been documented in many malignancies as participating in the progression of cancer cells. Here, we present a novel EGFR tyrosine kinase inhibitor, ZZC4, and examine its effect on cancer cell proliferation, migration, and tumor-bearing xenograft models. MAIN METHODS: The antiproliferative effect of ZZC4 was assessed in vitro by MTT assay, colony formation, and wound healing assay and in vivo with tumor-bearing xenograft nude mice. Further, Western blotting analysis and computational network pharmacology were used to explore and understand the mechanism of ZZC4. KEY FINDINGS: The results showed that ZZC4 potently inhibited the proliferation of lung, breast, and melanoma cells, and was more sensitive to lung cancer cells HCC827, H1975, and breast cancer cell T47D. In vitro findings were corroborated in vivo as results showed the suppressive effect of ZZC4 on HCC827 and H1975 tumor growth. Western blotting analysis confirmed that ZZC4 is an effective inhibitor of the EGFR pathways as it down-regulated p-EGFR, p-Akt, and p-MAPK. Computational molecular docking confirmed the strong binding affinity between ZZC4 and EGFR. Moreover, network pharmacology suggested that ZZC4 might play a suppressive role in the progression of malignancies with EGFR/PI-3K/Akt axis dysregulation or in cancer-related drug resistance. SIGNIFICANCE: Our study showed that ZZC4 is an anticancer drug candidate.

Epidemiological characteristics of HIV transmission in southeastern China from 2015 to 2020 based on HIV molecular network.

Objective: HIV/AIDS remains a global public health problem, and understanding the structure of social networks of people living with HIV/AIDS is of great importance to unravel HIV transmission, propose precision control and reduce new infections. This study aimed to investigate the epidemiological characteristics of HIV transmission in Fujian province, southeastern China from 2015 to 2020 based on HIV molecular network. Methods: Newly diagnosed, treatment-naive HIV/AIDS patients were randomly sampled from Fujian province in 2015 and 2020. Plasma was sampled for in-house genotyping resistance test, and HIV molecular network was created using the HIV-TRACE tool. Factors affecting the inclusion of variables in the HIV molecular network were identified using univariate and multivariate logistic regression analyses. Results: A total of 1,714 eligible cases were finally recruited, including 806 cases in 2015 and 908 cases in 2020. The dominant HIV subtypes were CRF01_AE (41.7%) and CRF07_BC (38.3%) in 2015 and CRF07_BC (53. 3%) and CRF01_AE (29.1%) in 2020, and the prevalence of HIV drug resistance was 4.2% in 2015 and 5.3% in 2020. Sequences of CRF07_BC formed the largest HIV-1 transmission cluster at a genetic distance threshold of both 1.5 and 0.5%. Univariate and multivariate logistic regression analyses showed that ages of under 20 years and over 60 years, CRF07_BC subtype, Han ethnicity, sampling in 2015, absence of HIV drug resistance, married with spouse, sampling from three cities of Jinjiang, Nanping and Quanzhou resulted in higher proportions of sequences included in the HIV transmission molecular network at a genetic distance threshold of 1.5% (p < 0.05). Conclusion: Our findings unravel the HIV molecular transmission network of newly diagnosed HIV/AIDS patients in Fujian province, southeastern China, which facilitates the understanding of HIV transmission patterns in the province.

Energy saving and carbon reduction schemes for hospital with photovoltaic power generation and system upgrading technology.

In order to help China achieve the double carbon target of total carbon peak and high-quality sustainable economic development, and to enrich the work and content of energy conservation and emission reduction in the building sector, the most complex and energy-consuming hospitals are taken as the key projects for energy conservation and emission reduction to carry out feasibility studies. The reasons for the high energy consumption of the existing hospital buildings were analysed, and it was proposed to upgrade the existing systems (including air conditioning, hot water system and intelligent control system) and to generate photovoltaic power for the existing buildings, taking into account the characteristics of the local climate. The results of the study showed that the energy saving and emission reduction effect of the hospital was obvious after the programme was adopted.

Influencing factors of early activity in patients with acute ischemic stroke based on social ecological model: A qualitative study. / åŸºäºŽç¤¾ä¼šç”Ÿæ€ç†è®ºæ¨¡åž‹çš„æ€¥æ€§ç¼ºè¡€æ€§è„‘å’ä¸­æ‚£è€ æ—©æœŸæ´»åŠ¨å½±å“å› ç´ çš„è´¨æ€§ç ”ç©¶.

OBJECTIVES: Acute ischemic stroke (AIS) is one of the main causes of disability in middle-aged and elderly people, and early activity plays an important role in functional recovery. This study aims to understand the factors that affect the implementation of early activity in patients with AIS and to provide reference for promoting early activity implementation and developing intervention strategies for AIS patients. METHODS: Using purposive sampling, 19 AIS patients and their caregivers who visited at Stroke Center in the Third Xiangya Hospital of Central South University and the Third Hospital of Changsha from June to December 2021, as well as 19 medical staff, hospital administrators, or community workers providing medical health services to stroke patients, were selected as interviewes. A semi-structured interview was conducted based on the social ecological theory model, and the Colaizzi seven-step method was used to analyze the interview data. RESULTS: According to qualitative interview results, the factors affecting early activity in AIS patients were summarized into 4 themes and 12 sub-themes: medical staff factors (insufficient knowledge and skills, insufficient knowledge of early activity, unclear division of responsibilities), patient factors (severity of the disease, lack of knowledge, psychological pressure, fear of falling), social environmental factors (lack of social support, shortage of human resources and rehabilitation equipment, insufficient medical insurance support), and evidence and norms (the evidence for early activity needs improvement, lack of standardized early activity procedures). CONCLUSIONS: Early activity in AIS patients is impacted by factors at multiple levels, including medical staff, patients, social environment, and evidence and norms. Developing comprehensive intervention strategies to address these factors can promote early activity implementation in AIS patients.

Can salivary lactate be used as an anaerobic biomarker?

Background: Salivary lactate has been suggested as a non-invasive anaerobic biomarker in sports medicine for decades, yet has not been widely applied until now. This study aimed to explore possible issues related to its application and suggest directions for future method improvement. Methods: A liquid chromatography-mass spectrometry (LC-MS) method for the determination of salivary lactate was developed, validated and applied on saliva samples collected from a group of professional sprinters (n = 20). The samples were collected via chewing a cotton ball for one minute and centrifuging it afterwards. The evaluation included variation with mouth rinse times, consistency at different sampling times, change after treadmill or cycle ergometer trainings, and association with blood lactate. Sample sizes were calculated prior to the study. One-way analysis of variance (ANOVA), intra-class correlation coefficients (ICC) and relative standard deviation (RSD) were used to evaluate data variances. Pearson correlation was applied to show correlation between salivary and blood lactate. Effect sizes and power were calculated following ANOVA and correlation analyses. Results: The RSD of the LC-MS method was 19.70%. Salivary lactate concentration was affected by mouth rinse times before sampling (ANOVA p = 0.025, η 2 = 0.40, 1 - ß = 0.99, ICC = 0.23, mean RSD of four sampling = 55.30%), and stabilized after mouth rinsing for three times. The concentrations at resting state across three weeks were consistent at group level (ANOVA p = 0.57, η 2 = 0.03, 1 - ß = 0.20), but varied greatly individually (ICC = 0.22, mean RSD = 56.16%). Salivary lactate level significantly increased after treadmill and cycle ergometer trainings (ANOVA p = 0.0002, η 2 = 0.46, 1 - ß = 0.9999 and ANOVA p = 0.0019, η 2 = 0.40, 1 - ß = 0.9993, respectively), and displayed positive correlation with blood lactate concentration (r = 0.61, p = 0.0004, 1 - ß = 0.9596). Significant difference between male and female participants was observed in none of the tests conducted in this study. Discussion: Salivary lactate was found to be a potential anaerobic biomarker. However, reproducible methods for sample collection and analysis, as well as more knowledge on the secretion mechanism and pattern of salivary lactate are required to make it a practical anaerobic biomarker.

The effects of sodium sulfite on Helicobacter pylori by establishing a hypoxic environment.

Helicobacter pylori (H. pylori) is an obligate microaerobion and does not survive in low oxygen. Sodium sulfite (SS) reacts and consume oxygen in solutions. The present study aimed to investigate the effects of SS on H. pylori. The effects of SS on oxygen concentrations in solutions and on H. pylori in vivo and in vitro were examined, and the mechanisms involved were explored. The results showed that SS decreased the oxygen concentration in water and artificial gastric juice. In Columbia blood agar and special peptone broth, SS concentration-dependently inhibited the proliferation of H. pylori ATCC43504 and Sydney strain-1 in Columbia blood agar or special peptone broth, and dose-dependently decreased the number of H. pylori in Mongolian gerbils and Kunming mouse infection models. The H. pylori was relapsed in 2 weeks withdrawal and the recurrence in the SS group was lower than that in the positive triple drug group. These effects were superior to positive triple drugs. After SS treatments, the cell membrane and cytoplasm structure of H. pylori were disrupted. SS-induced oxygen-free environment initially blocked aerobic respiration, triggered oxidative stress, disturbed energy production. In conclusion, SS consumes oxygen and creates an oxygen-free environment in which H. pylori does not survive. The present study provides a new strategy and perspective for the clinical treatment of H. pylori infectious disease.

Review on the Formulation, Existing Problems, and Practical Effects of Fitness Exercise Prescriptions for People With Intellectual Disabilities.

Compared with normal people, patients with intellectual disability have poor cardiopulmonary and muscle fitness levels, and their daily physical activity generally cannot reach the "guideline-recommended amount," which increases the risk of obesity and cardiovascular disease in this group. From the perspective of six elements of exercise prescription (frequency, intensity, time, form of exercise, amount of exercise, and progressive rate), this paper systematically reviews the current situation of the formulation and implementation of exercise prescription for patients with intellectual disabilities. The results show that the design idea of aerobic fitness exercise prescription for patients with intellectual impairment follows the six-element 5paradigm, but the insufficient recommended amount of each element is a common problem. In the design of muscle fitness exercise prescription, due to the differences of different exercise forms, the description of the six elements is very inconsistent. Although most prescription execution effects show that it is beneficial to improve cardiopulmonary and muscle fitness, there is a great debate on whether it is beneficial to improve body composition. People with intellectual disabilities are highly heterogeneous groups. In the initial stage of exercise intervention, the elements of exercise prescription need to be adjusted individually to obtain sustainable positive benefits.

Novel compound ZCJ14, a gefitinib analog, exhibited prominent anti-cancer effect among several cancer cell lines.

AIM: ZCJ14, a gefitinib analog, exhibited prominent anti-cancer effect both in vitro and in vivo. The present study aims to investigate the inhibitory effects of ZCJ14 on human cancer cells, and explored its possible mechanism of action. MAIN METHODS: The inhibitory effect of ZCJ14 on human-derived tumor cells in vitro was mainly measured by MTT and colony formation assays. The nude mouse xenograft models were established to figure out the inhibitory effect of ZCJ14 on solid tumors in vivo. Western blotting assays were used to detect the phosphorylation level of EGFR down-streaming proteins and the proteomic technique was used to study the proteome alterations of cancer cells triggered by ZCJ14. KEY FINDINGS: ZCJ14 inhibited the proliferation of A549 (lung cancer), HCT116 (colorectal cancer) and MCF-7 (breast cancer) cells in vitro with 48 h IC50 values of 0.83, 0.85 and 0.92 µM, respectively. It suppressed the growth of A549, NCI-H1975, NCI-H1299 and MCF-7, HCT116 tumors in mouse xenograft models, and had almost no toxicity. At the same dose, the inhibitory effect of ZCJ14 on solid tumors was better than the corresponding positive drugs. ZCJ14 does not exert anti-tumor effects through inhibition of EGFR pathway, but by enhancing steroid biosynthesis and inhibiting ubiquitin-mediated proteolysis. SIGNIFICANCE: Based on the excellent anti-tumor effect of ZCJ14 on human tumor cell lines, it can be used as an effective anti-tumor drug candidate. In addition, the results of proteomic study in this paper can provide clues for further study of the anti-tumor mechanism of ZCJ14.

Might female patients benefit more from bariatric surgery with respect to inflammation.

Background: Bariatric surgery is an effective method for severe obesity and its related comorbidities, in which inflammation plays a crucial role. The aim of this study was to investigate the changes of Neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) in patients undergoing laparoscopic sleeve gastrectomy (LSG) and to explore the related factors including gender. Methods: We retrospectively included 72 patients undergoing LSG in our hospital from 2017 to 2020. Clinical information, laboratory investigations as well as parameters derived from traditional and 2D strain echocardiography were collected. Univariate logistic model was used in myocardial performance index (MPI) and E/E' analysis. Univariate and Multivariate logistic model were used in NLR analysis. Results: At baseline, all patients had normal left ventricular ejection fraction (LVEF). The myocardial performance index (MPI) (OR = 1.218 (95%CI 1.040, 1.426); p = 0.0142) and E/E' (OR = 1.364 (95%CI 1.124, 1.655); p = 0.0017) were independently associated with CRP. LSG led to a significant decrease in inflammatory markers (NLR, 2.4 ± 1.59 vs.1.7 ± 0.86; CRP, 5.6 ± 3.17 vs. 2.1 ± 2.35 mg/L, respectively, both p < 0.001),which was more in NLR among female than male (OR = 3.14 (95%CI 1.112, 8.870); p = 0.031). Conclusions: The present study indicated a significant correlation between subclinical cardiac dysfunction and CRP among obese patients. Furthermore, female patients might benefit more from bariatric surgery on inflammation.

Effect of implementing enhanced recovery after surgery principles in the perioperative period of pediatric inguinal hernia.

OBJECTIVE: We aimed to investigate the effect of implementing enhanced recovery after surgery (ERAS) principles in the perioperative period of pediatric inguinal hernia (IH). METHODS: In this prospective study, 98 children undergoing surgery for IH in our hospital were randomly divided into the control group (n=49, routine nursing) and the study group (n=49, nursing care with ERAS principles). The anesthesia recovery period, time from end of surgery to first ambulation and to first anal exhaust, length of hospital stay, mental state before and after the intervention, pain level, incidence of complications, and family satisfaction with the nursing care were compared between the two groups. The recurrence rate of IH within half a year was recorded. RESULTS: Compared with the control group, the time from the end of surgery to first ambulation and to first anal exhaust and the length of hospital stay were shorter in the study group (all P<0.05). After the nursing intervention, both groups achieved better scores in mental state and pain level, and the improvement in the study group in mental state and pain level was greater than that in the control group (all P<0.05). Compared with the control group, the study group had higher family satisfaction with the nursing care and lower incidence of complications during hospitalization (both P<0.05). During the half-year follow-up, no recurrence was observed in both groups. CONCLUSION: The implementation of ERAS principles in the perioperative period of pediatric IH can help to relieve postoperative pain, reduce psychological discomfort, reduce the incidence of complications, and promote postoperative recovery in children.

Irreversible epidermal growth factor receptor inhibitor Z25h exhibits pronounced inhibition on non-small cell lung adenocarcinoma cell line Hcc827.

The epidermal growth factor receptor (EGFR) signaling is frequently activated in lung cancer. In our previous study, a new class of compounds containing pyrido[3,4-d]pyrimidine scaffold with an acrylamide moiety was designed as irreversible EGFR-tyrosine kinase inhibitors to overcome acquired EGFR-T790M resistance. In this study, we selected the most promising compound Z25h to further investigate its effects and the underlying mechanism against non-small cell lung adenocarcinoma cells in vitro. Four different non-small cell lung adenocarcinoma cell lines were selected to test the antiviability profile of Z25h, and Hcc827 was the most sensitive to the drug treatment. Z25h caused cell cycle arrest at G0-G1 phase, and triggered strong early apoptosis in Hcc827 cells at 0.1 µM and late apoptosis in A549, H1975 and H1299 cells at 10 µM by 48 h treatment. Z25h inhibited the activation of EGFR and its downstream PI3K/AKT/mTOR pathway in the four tested cell lines, leading to the inhibition of cellular biosynthetic and metabolic processes and the promotion of apoptotic process. However, the effect of Z25h on mitogen-activated protein kinase pathway varies from cell lines. In addition, Z25h sensitized H1975 cells to X-ray radiation, and it also enhanced the radiation effect on A549 cells, while no obvious effect of Z25h was observed on the cell viability inhibition of H1299 cells induced by radiation. Hereby, Z25h might be considered as a potential therapeutic drug candidate for non-small cell lung adenocarcinoma treatment.

LASP1 interacts with N-WASP to activate the Arp2/3 complex and facilitate colorectal cancer metastasis by increasing tumour budding and worsening the pattern of invasion.

LIM and SH3 protein 1 (LASP1) is a metastasis-related protein reported to enhance tumour progression in colorectal cancer (CRC). However, the underlying mechanism is still elusive. As the major biological and pathological functions of LASP1 are accomplished by its LIM and SH3 domains via protein-protein interactions, a yeast two-hybrid system was employed to screen novel LASP1-interacting proteins. N-WASP, a member of the Wiskott-Aldrich syndrome protein (WASP) family, was screened and identified as a LASP1-interacting protein overexpressed in CRC tissues. N-WASP could stimulate the migration and invasion of CRC cells in vitro and increase the formation of subcutaneous tumours, mesenteric implanted tumours and hepatic metastatic tumours. N-WASP could interact with and activate the Arp2/3 complex to stimulate actin polymerization, thus changing the migratory and invasive capabilities of CRC cells. The interaction of LASP1 with N-WASP did not influence the expression of N-WASP but recovered the reduced actin polymerization induced by N-WASP silencing. High N-WASP expression was detected in most clinical colorectal samples, and it was positively correlated with the expression of LASP1 and ARP3, as well as the tumour budding and pattern of invasion, but negatively correlated with host lymphocytic response. Our study suggests a new mechanism for LASP1-mediated CRC metastasis determined by exploring LASP1-interacting proteins and identifies N-WASP as a potential therapeutic target for CRC.

Determination of pharmacokinetic parameters of vitamin K1 in rats after an intravenous infusion.

Pharmacokinetic parameters of vitamin K1 have a large range of values in different literature. The aim of this study was to determine the pharmacokinetic parameters of vitamin K1 following post-constant speed intravenous infusion (PCSII) to provide rational pharmacokinetic parameters of vitamin K1 and compare these with results of noncompartmental analysis following intravenous injection (IV). After 15 hours intravenous infusion of vitamin K1 in rats, the logarithmic concentration-time curve of vitamin K1 was fit to a linear equation following PCSII (R2  = 0.9599 ± 0.0096). Then, half-time (T1/2 ), apparent volume of distribution (Vd ), and clearance rate (CL) were estimated successively. T1/2 of vitamin K1 was 4.07 ± 0.41 hour, CL was 89.47 ± 3.60 mL/h, and Vd was 525.38 ± 54.45 mL in rats following PCSII. There was no significant difference in pharmacokinetic parameters of vitamin K1 among different sampling times. For noncompartmental analysis, T1/2 and mean residence time (MRTINF ) for a sampling duration of 6h were shorter than those of 12 hours or 24 hours sampling duration following IV (P < .05, P < .01). In addition, T1/2 of vitamin K1 was obviously different from MRT-equated half-time (T1/2,MRT )(P < .05). Vd and CL of vitamin K1 following PCSII were larger than those following IV based on noncompartmental analysis (P < .01). The results demonstrated that drug distribution in the body was balanced and the Napierian logarithmic concentration-time curve of vitamin K1 fit to a linear equation following PCSII. Vitamin K1 has a long T1/2 and a relatively large Vd following PCSII.

Hydrogen Peroxide-Mediated Oxygen Enrichment Eradicates Helicobacter pylori In Vitro and In Vivo.

Helicobacter pylori is an important risk factor for gastric ulcers. However, antibacterial therapies increase the resistance rate and decrease the eradication rate of H. pylori Inspired by the microaerophilic characteristics of H. pylori, we aimed at effectively establishing an oxygen-enriched environment to eradicate and prevent the recurrence of H. pylori The effect and the mechanism of an oxygen-enriched environment in eradicating H. pylori and preventing the recurrence were explored in vitro and in vivo During oral administration and after drug withdrawal, H. pylori counts were evaluated by Giemsa staining in animal cohorts. An oxygen-enriched environment in which H. pylori could not survive was successfully established by adding hydrogen peroxide into several solutions and rabbit gastric juice. Hydrogen peroxide effectively killed H. pylori in Columbia blood agar and special peptone broth. Minimum inhibition concentrations and minimum bactericidal concentrations of hydrogen peroxide were both relatively stable after promotion of resistance for 30 generations, indicating that hydrogen peroxide did not easily promote resistance in H. pylori In models of Mongolian gerbils and Kunming mice, hydrogen peroxide has been shown to significantly eradicate and effectively prevent the recurrence of H. pylori without toxicity and damage to the gastric mucosa. The mechanism of hydrogen peroxide causing H. pylori death was related to the disruption of bacterial cell membranes. The oxygen-enriched environment achieved by hydrogen peroxide eradicates and prevents the recurrence of H. pylori by damaging bacterial cell membranes. Hydrogen peroxide thus provides an attractive candidate for anti-H. pylori treatment.

Label-Free Quantitative Proteomic Profiling of LAD2 Mast Cell Releasates Reveals the Mechanism of Tween-80-Induced Anaphylactoid Reaction.

PURPOSE: Tween-80 is one of the most important causes resulting in anaphylactoid reaction. However, its mechanism remains unclear. Proteomic characterizations of mast cells' excreta in response to Tween-80 are assayed to investigate the mechanism of anaphylactoid reaction. EXPERIMENTAL DESIGN: A label-free LCMS/MS-based proteomics is used to analyze Tween-80-stimulated Laboratory of Allergic Diseases 2 (LAD2) mast cells releasates. The results of proteomic are analyzed by bioinformatics analysis. Western blotting is used to verify the expression of proteins. RESULTS: Overall, endocytosis, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and calcium signaling pathways play important roles in Tween-80-induced LAD2 cells activation by bioinformatics analysis. The expressions of relative proteins including actin-related protein 2/3 complexes, vacuolar protein sorting-associated protein, phosphorylation of transcription factor of P105 and P65, phosphorylation of inositol 1,4,5-trisphosphate receptor (IP3 R), phosphoinositide phospholipase Cγ (PLCγ), and protein kinase C (PKC), are significantly increased in Tween-80 group compared to control. Tween-80 might be internalized via endocytosis, which induces degranulation by PLCγ/PKC pathways mediated calcium influx, and promotes the generation of inflammatory mediators via NF-κB pathway resulting in anaphylactoid reaction.