[Research progress of long-chain non-coding RNA in lipid metabolism reprogramming in primary hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is the most common liver malignant tumor with complex pathogenesis and a poor prognosis. Metabolic reprogramming has been recognized as one of the important cancer markers, and the liver, as an important organ for lipid metabolism in the human body, plays an important role in the process of the occurrence and development of HCC. More and more evidence shows that long-chain non-coding RNA (lncRNA) can influence the lipid metabolism process by regulating key enzymes and transcription factors, as well as being involved in the occurrence and development of HCC. Therefore, explicating the mechanism of lncRNA in lipid metabolism reprogramming is conducive to providing new targets and strategies for the diagnosis and treatment and improving the prognosis of HCC patients. This article summarizes the latest research progress on the involvement of lncRNA in the reprogramming process of HCC lipid metabolism.

[Research progress of non-coding RNA-encoding polypeptides in primary hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, with rapid progression and a poor prognosis. More and more studies have shown that there are small open reading frames (sORFs) on the molecular sequences of a large number of non-coding RNAs (ncRNAs), which can encode conserved peptides that play an important role in controlling the occurrence and development of HCC. This article introduces the discovery, prediction, and validation methods of ncRNA-encoding polypeptides and reviews its research progress, with the aim of providing new targets and ideas for early-stage diagnosis, targeted therapy, and prognosis assessment of HCC.

[Rethinking the marketing strategy of anti-tumor drugs by single-arm trials supported].

Single-arm trial refers to a clinical trial design that does not set up parallel control group, adopts open design, and does not involve randomization and blind method. These features, on the one hand, speed up the process of clinical trials, significantly shorten the time to market and meet the needs of patients with advanced malignancies, but also lead to the uncertainty of single-arm clinical trials themselves. Recently, the US Food and Drug Administration held a meeting of the oncologic drug advisory committee to discuss six tumor indications that have been accelerated approved, which once again triggered the discussion of single-arm trials. The basis of accelerated approval by single-arm trial is actually a compromise on the level of evidence-based medical evidence requirements after assessing the benefit risk. Therefore, the sponsor should strictly grasp the applicable conditions of single-arm trial in anti-tumor drugs and conduct single-arm trial scientifically. Post-marketing clinical trial should be implement as early as possible to ensure the benefit of patients. Based on the characteristics of single-arm trial, combined with two guidance relevant to single-arm trial issued by National Medical Products Administration recently, this article is supposed to propose and summarize the strategy of single-arm trial supporting the marketing of anti-tumor drugs.

[Clinical characteristics of children infected with different subtypes/genotypes of human respiratory syncytial virus in Beijing from 2009 to 2017].

Objective: To explore the different clinical characteristics of children infected with different subtype/genotype of human respiratory syncytial virus (HRSV) in Beijing. Methods: Respiratory specimens for positive HRSV were randomly collected from children with acute respiratory tract infection (ARTI) in the epidemic season of HRSV from November of each year to January of the next year during 2009 and 2017. G genes of HRSV were amplified and sequenced for subtyping and genotyping by bioinformatics analysis. Clinical data were collected and analyzed. Results: Out of 590 children, 376 (63.7%) with subtype A, and 214 (36.3) with subtype B. The annual dominant subtypes of HRSV from 2009 to 2017 were B-A-A-B-AB-A-A-B-A, respectively, whilst a total of 10 genotypes were detected with 95.8% assigned to genotype ON1 and NA1 of subtype A, and genotype BA9 of subtype B. Children infected with subtype B (96 cases, 44.9%) were more likely aged 0-3 month old than those with subtype A (118 cases, 31.4%) (P=0.001), and more likely to be admitted to Intensive Care Unit(ICU) ((124 cases, 57.9%) than those with subtype A (172 cases, 45.7%)) (P=0.005). Statistical significance were shown among children infected with genotype ON1, NA1 or BA9, in the possibility of infection in children aged 0-3 month (P=0.003), proportion of admission into ICU (P=0.007), length of stay in hospital (P=0.001), and clinical outcome (P=0.001), respectively. Conclusion: Children infected with different subtype or genotype of HRSV have different clinical characteristics, which stresses the important role of the monitoring HRSV subtypes and genotypes among children.

Rituximab is an effective treatment in patients with pemphigus vulgaris and demonstrates a steroid-sparing effect.

BACKGROUND: Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing steroid-related adverse events (AEs) is unproven. OBJECTIVES: To utilize data collected in a French investigator-initiated, phase III, open-label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV. METHODS: This was an independently conducted post hoc analysis of the moderate-to-severe PV subset enrolled in the Ritux 3 study. Patients were randomized to rituximab plus 0·5 or 1·0 mg kg-1 per day prednisone tapered over 3 or 6 months, or 1·0 or 1·5 mg kg-1 per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for ≥ 2 months, and 24-month efficacy and safety results were also reported. RESULTS: At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff ≥ 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one rituximab-plus-prednisone patient withdrew due to pregnancy. Overall, 24 of 36 patients (67%) on prednisone alone experienced a grade 3/4 CS-related AE vs. 13 of 38 patients (34%) on rituximab plus prednisone. CONCLUSIONS: In patients with moderate-to-severe PV, rituximab plus short-term prednisone was more effective than prednisone alone. Patients treated with rituximab had less CS exposure and were less likely to experience severe or life-threatening CS-related AEs. What's already known about this topic? Pemphigus vulgaris (PV) is the most common type of pemphigus. Corticosteroids, a standard first-line treatment for PV, have significant side-effects. Although their effects are unproven, adjuvant corticosteroid-sparing agents are routinely used to minimize steroid exposure and corticosteroid-related side-effects. There is evidence that the anti-CD20 antibody rituximab is effective in the treatment of patients with severe recalcitrant pemphigus and in patients with newly diagnosed pemphigus. What does this study add? This study provides a more detailed analysis of patients with PV enrolled in an investigator-initiated trial. Rituximab plus prednisone had a steroid-sparing effect and more patients achieved complete remission off prednisone. Fewer patients experienced grade 3 or grade 4 steroid-related adverse events than those on prednisone alone. This collaboration between academia and industry, utilizing independent post hoc analyses, led to regulatory authority approvals of rituximab in moderate-to-severe PV.

Lysobacter enzymogenes LE16 autolysates have potential as biocontrol agents-Lysobacter sp. autolysates as biofungicide.

AIMS: Biological techniques can manage plant diseases safely and in environmentally friendly ways, but their efficacy needs improvement. It is of the utmost importance to search for powerful microbes for the effective control of plant diseases. METHODS AND RESULTS: Unheated self-digestive solutions (SDS) that were heated at 100°C for 30 min(H-SDS) or stored for 12 months at room temperature (S-SDS) were prepared from Lysobacter enzymogenes LE16 broth culture to study their potential as biocontrol agents. This bacterium produced protease, phosphatase, lysozyme and siderophores in pure culture as well as 12 secondary metabolites including novel antibiotics lysobactin, WAP-8294A2 and mupirocin determined based on the antiSMASH 5.0.0 blast database. A poison plate assay revealed the antagonistic activities of SDS, H-SDS and S-SDS against an animal pathogenic bacterium Staphylococcus aureus, a phytopathogenic bacterium Pseudomonas syringae pv. tabaci, and numerous plant pathogenic fungi and oomycetes, including Colletotrichum gloeosporioides, Penicillium italicum, Alternaria alternate, Rhizoctonia solani, Didymella bryoniae, Sclerotinia sclerotiorum, Phytophthora nicotianae and Phytophthora capsici. The greenhouse experiment showed that SDS was highly effective in controlling pepper blight disease, which is caused by P. capsici. Compared with only pathogen inoculation, the application of SDS to the soil in preventive or curative treatments significantly reduced the disease incidence and index with relatively high control efficacy of 86·2-93·1%. CONCLUSIONS: SDS enriched lytic enzymes, siderophores and antibiotics, has a wide antimicrobial spectrum, and shows potential as a new, safe and effective biocontrol agent against plant diseases. SIGNIFICANCE AND IMPACT OF THE STUDY: Autolysates of the new biocontrol bacterium L. enzymogenes LE16 demonstrated the potential for industrial production and commercial use as a promising biocontrol agent in agriculture.

Effects of a nutrient-dense formula compared with a post-discharge formula on post-discharge growth of preterm very low birth weight infants with extrauterine growth retardation: a multicentre randomised study in China.

BACKGROUND: Post-discharge optimal growth and nutritional intake have beneficial effects for neurodevelopment in preterm very low birth weight infants (VLBWIs) with extrauterine growth retardation (EUGR). The present study aimed to compare the effects of a nutrient-dense formula (NDF) to a post-discharge formula (PDF) on post-discharge growth of preterm VLBWIs with EUGR. METHODS: Forty-eight preterm VLBWIs with EUGR at discharge were randomised to receive NDF (100 kcal per 100 mL; 2.6 g protein per 100 mL) or PDF (74 kcal per 100 mL; 1.95 g protein per 100 mL) for 1-6 months until body weight reached the 50th percentile on growth charts with corrected age. Volume, nutrient intake, anthropometry and biochemistry data were collected. RESULTS: Volume intake was lower in the NDF group than the PDF group during the first 2 months of feeding (P = 0.039 and 0.018, respectively).There were no significant differences in volume intake during months 2-6 of feeding. Energy, protein, carbohydrate and fat intake were higher in the NDF group during months 1-6 of feeding. There were no significant differences in weight, length, and head circumference Z-scores during months 1-6 between the two groups. The △length Z-score from discharge to month 6 was significantly higher in the NDF group than the PDF group (P = 0.043). No differences existed between the two groups with respect to biochemistry. CONCLUSIONS: After discharge, preterm VLBWIs with EUGR fed a NDF gain anthropometric parameter Z-scores similar to those for a PDF within 6 months of follow-up. A NDF leading to gain in length requires further follow-up.

[Clinical research and drug review of epidermal growth factor receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer].

Lung cancer is the most frequently diagnosed cancer and the most common cause of cancer mortality in China. Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancers. The mutation rate of epidermal growth factor receptor (EGFR) gene is relatively high, accounts for 32%~38% of all NSCLC. During the last decade, the application of EGFR specific tyrosine kinase inhibitors (TKI) significantly improved prognosis of NSCLC patients with sensitive EGFR mutations. Thus, the research and development of third generation EGFR-TKI have entered the period of rapid development. The fourth generation EGFR-TKI which targeting EGFR C797S has even begun clinical development in China. This review will discuss the clinical research and drug review of EGFR-TKI from the perspective of drug review.

Reliability and validity of the Advanced Basal Cell Carcinoma Index (aBCCdex).

BACKGROUND: Patient-reported outcome (PRO) questionnaires were recently developed specifically for use with patients with advanced basal cell carcinoma (aBCC) and basal cell carcinoma naevus syndrome (BCCNS). OBJECTIVES: To evaluate the measurement properties of PRO questionnaires for use in patients with aBCC or BCCNS. METHODS: In total 129 patients from 10 clinical sites in the U.S.A. and the BCCNS Support Network completed the two newly developed questionnaires multiple times over 3 months. Patients also completed the Skindex-16 and the 12-Item Short-Form Health Survey as collateral measures. Psychometric properties of the questionnaires were evaluated, including internal consistency and test-retest reliability, construct and known-groups validity, and responsiveness. RESULTS: Based on the results of exploratory factor analysis and clinical input, the two newly developed questionnaires were combined into a single questionnaire, called the aBCCdex, which is relevant for patients with both aBCC and BCCNS. The internal consistency reliability was acceptable, and all aBCCdex scale scores correlated significantly with conceptually similar scales. When divided into groups that differed based on scores from collateral measures, aBCCdex scale scores differentiated between groups (known-groups validity) and were responsive to change. CONCLUSIONS: The aBCCdex is a brief and comprehensive questionnaire appropriate for use with patients with aBCC and BCCNS. Its reliability and validity have been confirmed. Further research is necessary to estimate the minimally important difference in a larger patient population.

APOA5 -1131T>C and APOC3 -455T>C polymorphisms are associated with an increased risk of coronary heart disease.

The aim of this study was to investigate correlations between apolipoprotein A-V (APOA5) -1131T>C and apolipoprotein C-III (APOC3) -455T>C polymorphisms and coronary heart disease (CHD). PubMed, Ovid, Cochrane Library, Embase, China National Knowledge Infrastructure, and Wanfang databases were searched using combinations of keywords relating to these polymorphisms and CHD. Studies retrieved from database searches were screened using our stringent inclusion and exclusion criteria, and Comprehensive Meta-Analysis Version 2.0 software was used for statistical analyses. In total, 115 studies were initially retrieved and after further selection, 11 were included in the meta-analysis. These 11 articles comprised 4840 patients with CHD in the case group and 4913 healthy participants in the control group. Meta-analysis revealed that APOA5 -1131T>C and APOC3 -455T>C polymorphisms increased CHD risk. In addition, subgroup analysis by ethnicity showed that while the -1131T>C polymorphism elevated the risk of CHD in the Caucasian population under both allelic and dominant models, this increased risk was observed only under a dominant model in the Asian population. The results of our meta-analysis point to a strong link between both APOA5 -1131T>C and APOC3 -455T>C polymorphisms and an increased risk of CHD. Thus, these polymorphisms constitute important predictive indicators of CHD susceptibility.

[Pathogenic agents causing acute respiratory tract infections in pediatric patients in Spring, 2023, in Beijing].

Objective: To explore the pathogenic agents of acute respiratory infection (ARI) in children in Beijing. Methods: In the cross-sectional study, 3 groups of children from different departments were enrolled from Feb 6th, 2023 (6th week) to May 28th (21th week), 2023, including influenza-like case group from emergency department for nucleic acid testing of influenza virus (Flu) and human metapneumovirus (HMPV), the outpatient ARI group under nucleic acid testing for Flu, respiratory syncytial virus (RSV), adenovirus (ADV), and parainfluenza virus (PIV), and the inpatient ARI group under nucleic acid testing for Flu, RSV, HMPV, ADV, human bocavirus (HBoV), Rhinovirus (Rh), PIV, coronavirus (HCoV), Mycoplasma pneumoniae (Mp) and Chlamydia pneumonia (Cp). Results: There were 320 influenza-like cases enrolled, including 192 males and 128 females, aged 4.7 (3.6, 6.9) years, and 117 cases (36.6%) positive for Flu A, which contained similar proportion of pandemic H1N1 (H1N1) 47.0% (55/117) and H3N2 53.0% (62/117), and 13 cases for HMPV 4.1% (13/320). The rate of Flu reached its peak at the 10th week, with H1N1 as the predominant one from the 6th to 9th week (10.0%-50.0%) and then H3N2 from the 10th to 16th week (15.0%-90.0%). HMPV was detected from the 15th week 5.0% (1/20), and then reached to 30.0% (6/20) at the 20th week. In the outpatient ARI group, 7 573 were enrolled, including 4 131 males and 3 442 females, aged 4.0 (2.1, 5.3) years, and the highest positive rate for RSV 32.9% (2 491/7 573), followed by Flu A 12.1% (915/7 573). The dominant one was Flu A in weeks 6-14 (23.2%-74.7%), then RSV in the 15th week 24.8% (36/145). In the inpatient ARI group, 1 391 patients were enrolled, including 804 males and 587 females, aged 3.3 (0.4, 5.8) years, and the highest positive rate for Rh 18.7% (260/1 391), followed by RSV 12.4% (173/1 391), Flu A 10.2% (142/1 391, of which 116 cases (81.7%) were H1N1, and 26 cases (18.3%) were H3N2) and HMPV 3.1% (43/1 391). H1N1 was detected from the 7th week 10% (6/60), to peak in the 11th week 31.8% (21/66). H3N2 was detected from the 8th week 1.5% (1/68), and then kept in low level. The proportion of H1N1 among Flu was 81.7% (116/142) in the inpatient ARI group. RSV was detected from 12th week 1.3% (1/80), reaching 30.4% (35/115) at 19th week. The positive rate of HMPV reached 12.1% (14/116) at 21th week. Conclusions: In the spring of 2023, the first one in Beijing is the Flu epidemic, with H1N1 being the predominant one in the early stage and H3N2 in the later stage. Then, there is a postponed RSV epidemic and an increased HMPV detection. In addition, nucleic acid testing for outpatient children should be strengthened to provide early warning of epidemics.

[Outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network].

Objective: To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021. Methods: This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results: Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions: With the increasing number of extremely preterm infants at 22-25 weeks' gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.

Treatment of hydrogen molecule abates oxidative stress and alleviates bone loss induced by modeled microgravity in rats.

UNLABELLED: Treatment with molecular hydrogen alleviates microgravity-induced bone loss through abating oxidative stress, restoring osteoblastic differentiation, and suppressing osteoclast differentiation and osteoclastogenesis. INTRODUCTION: Recently, it has been suggested that hydrogen gas exerts a therapeutic antioxidant activity by selectively reducing cytotoxic reactive oxygen species (ROS). The aim of the present study was to elucidate whether treatment with molecular hydrogen alleviated bone loss induced by modeled microgravity in rats. METHODS: Hindlimb suspension (HLS) and rotary wall vessel bioreactor were used to model microgravity in vivo and in vitro, respectively. Sprague-Dawley rats were exposed to HLS for 6 weeks to induced bone loss and simultaneously administrated with hydrogen water (HW). Then, we investigated the effects of incubation with hydrogen-rich medium (HRM) on MC3T3-E1 and RAW264.7 cells exposed to modeled microgravity. RESULTS: Treatment with HW alleviated HLS-induced reduction of bone mineral density, ultimate load, stiffness, and energy in femur and lumbar vertebra. Treatment with HW alleviated HLS-induced augmentation of malondialdehyde content and peroxynitrite content and reduction of total sulfhydryl content in femur and lumbar vertebra. In cultured MC3T3-E1 cells, incubation with HRM inhibited modeled microgravity-induced ROS formation, reduction of osteoblastic differentiation, increase of ratio of receptor activator of nuclear factor kappa B ligand to osteoprotegerin, inducible nitric oxide synthetase upregulation, and Erk1/2 phosphorylation. In cultured RAW264.7, incubation with HRM aggravated modeled microgravity-induced ROS formation, osteoclastic differentiation, and osteoclastogenesis. CONCLUSION: Treatment with molecular hydrogen alleviates microgravity-induced bone loss in rats. Molecular hydrogen could thus be envisaged as a nutritional countermeasure for spaceflight but remains to be tested in humans.

Insulin resistance in first-trimester pregnant women with pre-pregnant glucose tolerance and history of recurrent spontaneous abortion.

Insulin resistance (IR) has been reported to play an important role in recurrent spontaneous abortion (RSA) among patients with polycystic ovary syndrome (PCOS). However, scanted materials exist regarding the independent effect of IR on RSA. The aim of this study is to investigate the status of IR in first trimester pregnant patients with normal pre-pregnant glucose tolerance and history of RSA. This two-center case-control study enrolled totally 626 first trimester pregnant women including 161 patients with a history of recurrent spontaneous abortion, who were pre-pregnantly glucose-tolerant according to oral glucose tolerance test (OGTT), and 465 women with no history of abnormal pregnancies of any kind. Clinical, biochemical and hormonal parameters were simultaneously measured in all participants. Serum beta-HCG, estradiol, progesterone, fasting plasma glucose and fasting plasma insulin levels, as well, the calculated homeostasis model assessment of insulin resistance index (HOMA-IR), fasting plasma glucose/insulin ratio(G/I) and pregnancy outcome were analyzed and compared. Serum beta-HCG and progesterone were found to be significantly lower in RSA group compared to controls. Subjects in RSA group were found to have higher HOMA-IR and lower G/I ratio than those in control group. Serum beta-HCG and progesterone were negatively correlated with HOMA-IR, and positively with G/I ratio even after adjustment for BMI. The spontaneous abortion rate within first trimester pregnancy of RSA patients was significantly higher than that in controls. In conclusion, woman with recurrent spontaneous abortion and normal pre-pregnant glucose metabolism tends to be more insulin resistant during first trimester pregnancy than healthy controls, no matter whether she has PCOS or not. Insulin resistance might be one of the direct causes that lead to recurrent abortion.

Pharmacokinetics of tulathromycin and its metabolite in swine administered with an intravenous bolus injection and a single gavage.

Tulathromycin is a macrolide antimicrobial agent proposed for therapeutic use in treatment of porcine and bovine respiratory disease. In this study, the absolute bioavailability of tulathromycin solution was investigated in pigs. Eight pigs, with body weight of 20.5 ± 1.6 kg, were given a single dose of tulathromycin at 2.5 mg/kg oral (p.o.) and intravenous (i.v.) in a crossover design. The plasma concentrations of tulathromycin and its metabolite were determined by LC-MS/MS method, and the pharmacokinetic parameters of tulathromycin were calculated by noncompartmental analysis. After p.o. administration, the maximum plasma concentration (C(max) ) was 0.20 ± 0.05 µg/mL at 3.75 ± 0.71 h. The terminal half-life (t(1/2λz) ) in plasma was 78.7 ± 6.75 h, and plasma clearance (Cl/F) was 1.14 ± 0.28 L/h/kg. After i.v. injection, plasma clearance (Cl) was 0.580 ± 0.170 L/h/kg, the volume of distribution (Vz) was 64.3 ± 21.2 L/kg, and the t(1/2λz) was 76.5 ± 13.4 h. In conclusion, an analytical method for the quantification of tulathromycin and its metabolite in plasma in swine was developed and validated. Following p.o. administration to pigs at 2.5 mg/kg b.w., tulathromycin was rapidly absorbed and the systemic bioavailability was 51.1 ± 10.2.

[Clinical characteristics of human adenovirus infection in hospitalized children with acute respiratory infection in Beijing].

Objective: To compare the clinical characteristics of different types of human adenovirus (HAdV) infection in hospitalized children with acute respiratory infection in Beijing, and to clarify the clinical necessity of adenovirus typing. Methods: In a cross-sectional study, 9 022 respiratory tract specimens collected from hospitalized children with acute respiratory infection from November 2017 to October 2019 in Affiliated Children's Hospital, Capital Institute of Pediatrics were screened for HAdV by direct immunofluorescence (DFA) and (or) nucleic acid detection. Then the Penton base, Hexon and Fiber gene of HAdV were amplified from HAdV positive specimens to confirm their HAdV types by phylogenetic tree construction. Clinical data such as laboratory results and imaging data were analyzed for children with predominate type HAdV infection using t, U, or χ2 test. Results: There were 392 cases (4.34%) positive for HAdV among 9 022 specimens from hospitalized children with acute respiratory infection. Among those 205 cases who were successfully typed, 131 were male and 74 were female, age of 22.6 (6.7, 52.5) months,102 cases (49.76%) were positive for HAdV-3 and 86 cases (41.95%), HAdV-7, respectively, while 17 cases were confirmed as HAdV-1, 2, 4, 6, 14 or 21. In comparison of clinical characteristics between the predominate HAdV type 7 and 3 infection, significant differences were shown in proportions of children with wheezing (10 cases (11.63%) vs. 25 cases (24.51%)), white blood cell count >15 ×109/L (4 cases (4.65%) vs.14 cases (13.73%)), white blood cell count <5×109/L (26 cases (30.23%) vs.11 cases (10.78%)), procalcitonin level>0.5 mg/L (43 cases (50.00%) vs. 29 cases (28.43%)), multilobar infiltration (45 cases (52.33%) vs.38 cases (37.25%)), pleural effusion (23 cases (26.74%) vs. 10 cases (9.80%)), and severe adenovirus pneumonia (7 cases (8.14%) vs. 2 cases (1.96%)) with χ²=5.11, 4.44, 11.16, 9.19, 4.30, 9.25, 3.91 and P=0.024, 0.035, 0.001, 0.002, 0.038, 0.002, 0.048, respectively, and also in length of hospital stay (11 (8, 15) vs. 7 (5, 13) d, Z=3.73, P<0.001). Conclusions: HAdV-3 and 7 were the predominate types of HAdV infection in hospitalized children with acute respiratory tract infection in Beijing. Compared with HAdV-3 infection, HAdV-7 infection caused more obvious inflammatory reaction, more severe pulmonary symptoms, longer length of hospital stay, suggesting the clinical necessity of further typing of HAdVs.

Analytical determination and pharmacokinetics of major metabolites of carbasalate calcium in broilers following oral administration.

As a newer anti-inflammatory agent, carbasalate calcium is used in various animal species. In this study, the pharmacokinetics of carbasalate calcium was investigated in broilers. Broilers, with body weight of 2.0 ± 0.3 kg, were administrated carbasalate calcium soluble powder at a single dose of 40 mg/kg body weight orally. The plasma concentrations of its metabolites, aspirin (ASA), salicylic acid (SA) and gentisic acid (GA) were determined by LC-MS/MS method and the pharmacokinetic parameters were calculated by noncompartmental analysis. After oral administration of carbasalate calcium, the plasma drug concentration for ASA, SA and GA reached a peak (C(max) ) of 8.88 ± 1.31, 42.6 ± 4.62 and 10.1 ± 2.16 µg/mL at 0.170, 2.00 and 2.00 h, respectively. The terminal half-life (t(1/2λz) ) of ASA, SA and GA was 11.2 ± 8.04, 23.7 ± 17.1 and 28.6 ± 4.90 h, respectively. In conclusion, analytical method for the quantification of ASA, SA and GA in plasma in the broilers was developed and validated. In broilers, carbasalate calcium is quickly metabolized in ASA and ASA is rapidly converted to SA and one of the metabolites of SA is GA.

Inhibition of cytochrome P450 2A participating in coumarin 7-hydroxylation in pig liver microsomes.

Five commonly used human cytochrome P450 (CYP) inhibitors were examined for their effects on coumarin 7-hydroxylase (CYP2A) activity in pig liver microsomes. The K(m) and V(max) values for coumarin 7-hydroxylation in pig liver microsomes were estimated to be 1 µm and 0.26 nmol·mg/min, respectively. The following human CYP inhibitors caused little or no inhibition of CYP2A as defined by a K(i) > 200 µm: quinidine (CYP2D6), troleandomycin (CYP3A4), and sulfaphenazole (CYP2C9). The other two human CYP inhibitors were classified as strong inhibitors of CYP2A: 8-methoxypsoralen (CYP2A6) and α-naphthoflavone (CYP1A1/2). In the absence of a preincubation period, 8-MOP inhibited the 7-hydroxylation of coumarin with a K(i) value of 1.1 µm, which decreased to 0.1 µm when 8-MOP was preincubated with pig liver microsomes for 3 min. α-Naphthoflavone inhibited the 7-hydroxylation of coumarin with a K(i) value of 32 µm, which did not increase ability to inhibitor CYP2A when α-naphthoflavone was preincubated with pig liver microsomes for 3 min. These results of this study suggest that 8-MOP is a potent, mechanism-based inhibitor of pig CYP2A activity in pig liver microsomes.

Conversion of monocytes to cells capable of anchorage-independent growth in vitro.

We investigated the time-course involved in the conversion of mouse blood monocytes in vitro in cells capable of anchorage-independent growth. Two criteria were used to define when monocytes were fully converted to cells similar to mononuclear phagocytes present in inflammatory exudate, such as thioglycollate medium (TM)-elicited peritoneal exudate. They were the production of high levels of plasminogen activators and an ability to undergo anchorage-independent growth. Resident peritoneal macrophages were used as controls and for comparison. Our studies indicated that monocytes, but not resident peritoneal macrophages, could be converted to cells similar to TM-elicited mononuclear phagocytes after 2 d in culture.