[Efficacy and safety of Anlotinib in the treatment of advanced sarcoma].

Objective: Patients with advanced sarcomas have a dismal prognosis with few effective therapies. The purpose of this study was to evaluate the efficacy and safety of anlotinib in the treatment of advanced sarcoma and to explore the relationship between adverse events (AEs) and efficacy. Methods: Data from 45 advanced sarcoma patients who received anlotinib monotherapy at Affiliated Cancer Hospital of Zhengzhou University between June 2018 and August 2021 were retrospectively analyzed. According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1, the objective remission rate (ORR) and disease control rate (DCR) were calculated, and the progression free survival (PFS) and treatment-related AEs were recorded and analyzed. Survival analysis was conducted using the Kaplan-Meier survival rates were compared using the Log rank test. Results: Forty patients were treated for more than 1.5 months and received efficacy evaluation. The ORR and DCR after 3 months were 7.5%(3/40) and 80.0%(32/40), respectively. The overall ORR was 2.5%(1/40), the total DCR was 27.5%(11/40), and the median progression-free survival (m-PFS) was 6.70 months; The m-PFS of alveolar soft tissue sarcoma (ASPS) was 10.27 months, which was significantly longer than that of other subtypes of sarcoma (P=0.048). In addition, the DCR of ASPS and synovial sarcoma (SS) was significantly better than that of osteosarcoma (P<0.05). The most common AEs were elevated thyroid stimulating hormone (17.8%, 8/45), anemia (15.6%, 7/45), fatigue (11.1%, 5/45). Five patients developed grade 3 AEs after treatment; The PFS of patients with hand-foot syndrome after treatment was significantly longer than that of patients without hand-foot syndrome (14.10 vs 6.00, P=0.024). Conclusions: The efficacy of anlotinib in the treatment of ASPS and SS is better than that of other subtypes. The PFS in the group with hand-foot syndrome was significantly longer than that of the group without hand-foot syndrome.

[Gene mutation profiles and clinicopathological features of patients with non-small cell lung cancer harboring KRAS G12C mutation: a single-center retrospective study].

Objective: To accurately screen non-small cell lung cancer (NSCLC) patients with KRAS G12C mutation and to evaluate their clinicopathological features, prognostic factors and current treatment status. Methods: A total of 19 410 NSCLC cases diagnosed at the Department of Pathology of Shanghai Chest Hospital, Shanghai, China from January 2018 to September 2021 were retrospectively reviewed, and the cases with KRAS gene mutation detected by next-generation sequencing were included. The clinicopathological and genetic mutation data of these cases were collected and analyzed. Results: A total of 1 633 (8.4%) NSCLC patients carried a KRAS gene mutation, among whom G12C was the most frequent (468 cases, 28.7%) mutant subtype. The mutation was more commonly found in males (414/468, 88.5%), patients with a history of smoking (308/468, 65.8%), and patients with a pathological type of invasive adenocarcinoma (231/468, 49.4%). The most common co-mutated genes in KRAS G12C mutant NSCLC were TP53 (52.4%, 245/468), STK11 (18.6%, 87/468) and ATM (13.2%, 62/468). The proportion of PD-L1 expression (≥1%) in KRAS G12C mutant NSCLC was significantly higher than that in patients without G12C mutation [64.3% (90/140) vs. 56.1% (193/344), P=0.014]. Immune checkpoint inhibitors (ICIs) treatment significantly prolonged progression-free survival (PFS) in NSCLC patients (10.0 months vs. 5.0 months, P=0.011). However, combination of chemotherapy and ICIs with anti-angiogenesis inhibitors or multi-target inhibitors did not significantly improve PFS in patients with KRAS G12C mutant NSCLC (P>0.05). Patients with KRAS G12C mutation NSCLC treated with ICIs and KRAS G12C patients with TP53 mutation had significantly longer median PFS than those with STK11 mutation (9.0 months vs. 4.3 months, P=0.012). Conclusions: Patients with KRAS G12C mutant NSCLC have relatively higher levels of PD-L1 expression and can benefit from ICIs treatment. The feasibility of chemotherapy, ICIs therapy and their combination needs further investigation.

[Analysis of clinical features and poor prognostic factors of acute hematogenous osteomyelitis in children].

Objective: To analyze the clinical characteristics, pathogenic bacteria, complications and risk factors of prognosis of acute hematogenous osteomyelitis in children. Methods: The clinical manifestations, laboratorg tests, etiological charateristics and clinical data of 107 patients with acute hematogenous osteomyelitis admitted to Beijing Children's Hospital from January 2017 to December 2020 were retrospectively analyzed. According to the drug sensitivity results of Staphylococcus aureus, the group was divided into methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA) group; according to the presence or absence of complications, the group was divided into the group with and without complications; according to the prognosis of the follow-up children, the group was divided into good prognosis and poor prognosis. The χ2 test or Mann-Whitney U test used for comparison between groups, and Logistic regression was used to analyze the risk factors for complications and prognosis. Results: Of the 107 patients, 62 were males and 45 were females. The age of presentation was 5.6 (1.7, 10.0) years, including 5 patients (4.7%) age from >28 days to 3 months, 46 patients (43.0%) age from >3 months to 5 years, 43 patients (40.2%)>5-12 years of age, and 13 patients (12.1%)>12-18 years of age. The first symptoms were acute fever in 35 patients (32.7%), limb pain in 24 patients (22.4%), and fever with limb pain in 23 patients (21.5%). Pathogen culture was positive in 75 patients (70.1%), Streptococcus pyogenes, Salmonella enterica and Escherichia coli in 1 case (1.4%) each, and Staphylococcus aureus in 72 cases (96.0%), among them, 47 cases were MSSA, 22 cases were MRSA, and 3 cases had positive reports of Staphylococcus aureus from other hospitals without drug-sensitive tests. The proportion of infected children living in rural areas and receiving surgical treatment was higher in the MRSA group than in the MSSA group (14 cases (63.6%) vs. 18 cases (38.3%) and 21 cases (95.5%) vs. 33 cases (70.2%), χ2=3.87, 4.23, both P<0.05). Sixty-five children had no complications while 42 children (39.3%) suffered from complications. Common complications consisted of 19 cases (17.8%) of sepsis, 17 cases (15.9%) of septic arthritis, and 12 cases (11.2%) of venous thrombosis. The group with complications showed higher mental changes, decreased appetite and (or) weakness, positive pathogenic cultures, and time from admission to surgery than the group without complications (18 cases (42.9%) vs. 9 cases (13.8%), 20 cases (47.6%) vs. 12 cases (18.5%), 34 cases (81.0%) vs. 41 cases (63.1%), 3.5 (2.0, 6.0) vs. 2.0 (1.0, 4.0) d,χ2=11.38, 10.35, 3.89, Z=2.21, all P<0.05). The poor prognosis group had more comorbidities, combined local complications, and positive aureus than the good prognosis group (10/15 vs. 34.9% (30/86), 7/15 vs. 17.4% (15/86), 14/15 vs. 61.6% (53/86), χ2=5.39, 6.40, 4.42, all P<0.05). Multifactorial Logistic regression analysis showed that acute phase C-reactive protein (CRP) was both an independent risk factor for complications (OR=1.01, 95%CI 1.01-1.02) and an independent risk factor for poor prognosis (OR=1.01, 95%CI 1.00-1.02). Conclusions: The first symptoms of acute hematogenous osteomyelitis are acute fever, limb pain, and fever with limb pain are most common. Staphylococcus aureus is the most common pathogenic organism. Those with loss of appetite and (or) weakness, mental changes, positive pathogenic cultures, and longer time between admission and surgery are prone to complications. Those with complications, combined local complications, and positive for Staphylococcus aureus had a poor prognosis. Elevated CRP is an independent risk factor not only for complications but for poor prognosis as well.

[Characteristics and recovery of hearing loss in 573 patients with bacterial meningitis].

Objective: To analyze the characteristics and prognosis of hearing loss in children with bacterial meningitis. Methods: This was a single-center retrospective cohort study. Patients diagnosed with bacterial meningitis who were hospitalized in Beijing Children's Hospital between 2010 and 2016 and older than 28 days and younger than 18 years at symptom onset were included in this study (n=573). All clinical information including hearing assessment results during hospitalization were reviewed. All patients with hearing loss were followed up to repeat their hearing test and assess their hearing condition with parents' evaluation of aural and (or) oral performance of children (PEACH). Patients were grouped according to their hearing assessment results, and Logistic regression analysis was used to analyze the risk factors for hearing loss in patients with bacterial meningitis. Results: Five hundred and seventy-three patients were enrolled in this study, including 347 males and 226 females. The onset age ranged from 29 days to 15.8 years. Two hundred and forty-six patients had identified causative pathogens, among whom 92 cases (37.4%) were pneumococcal meningitis cases. Hearing loss was found in 160 cases (27.9%) during hospitalization, involving 240 ears. Permanent hearing loss was found in 20 cases (16.9%), involving 32 ears. In the patients with permanent hearing loss, 87.5% (28/32) of ears were identified as severe or profound hearing loss during hospitalization. Logistic regression analysis showed that dystonia, the protein concentration level in cerebrospinal fluid>1 g/L, glucose concentration level lower than 1 mmol/L and subdural effusion were independent risk factors for hearing loss (OR=2.426 (1.450-4.059), 1.865 (1.186-2.932), 1.544 (1.002-2.381) and 1.904 (1.291-2.809)). Conclusions: Hearing loss is a common sequela of bacterial meningitis in children. Most patients have transient hearing loss, but patients with severe or profound hearing impairment have a higher risk of developing permanent hearing loss.

[Effects of evodiamine on carbon tetrachloride-induced liver fibrosis mice based on modulating gut microbiota].

Objective: To access the effects of evodiamine on carbon tetrachloride (CCl(4)) -induced liver fibrosis mice and study the mechanism based on modulating gut microbiota. Methods: From August 2019, 30 SPF male C57BL/6 mice were randomly divided into normal, model and evodiamine groups. Mice in control group received intraperitoneal injection of olive oil (2 ml/kg, twice per week) for 6 weeks. Mice in model and evodiamine groups received intraperitoneal injection of 20% CCl(4) (2 ml/kg, twice per week) for 6 weeks to induce liver fibrosis mice. Then, mice in evodiamine group received orally of evodiamine (18 mg/kg) for 4 weeks. The levels of serum alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , albumin (ALB) and total protein (TP) were detected. The pathological changes of liver tissue were observed. The effects of evodiamine on the abundance and diversity of intestinal microflora in liver fibrosis mice were determined. The mRNA and protein expression levels of inflammatory factors[interleukin-6 (IL-6) , interleukin-1ß (IL-1ß) , and tumor necrosis factor α (TNF-α) ] in liver tissue were measured. Results: Compared with the normal group, the body weight, serum ALB and TP levels of the model group were decreased, the liver index, ALT and AST levels were increased, and the intestinal flora Shannon and Simpson indexes were decreased (P<0.01) . Compared with the normal group, the abundance of Lactobacillus, Akkermansia and Bacteroides in the feces of the model group decreased, while the abundance of Enterococcus and Lachnoclostridium increased (P<0.01) . Compared with the normal group, the mRNA and protein expressions levels of IL-6, IL-1ß, and TNF-α in the liver tissue of the model group were significantly increased (P<0.01) . Compared with the model group, evodiamine could reduce liver index and serum ALT and AST levels, increase ALB and TP levels (P<0.05) , improve inflammatory cell infiltration and fibrosis degree in liver tissue, and up regulate intestinal flora Shannon and Simpson indexes in liver fibrosis mice (P<0.05) . Compared with the model group, evodiamine could increase the abundance of Lactobacillus, Akkermansia, Bacteroides, and reduce the abundance of Enterococcus and Lachnoclostridiun (P<0.05) . Compared with the model group, evodiamine could reduce the mRNA and protein levels of IL-6, IL-1ß and TNF-α in liver tissue of liver fibrosis mice (P<0.05) . Conclusion: Evodiamine can ameliorate CCl(4)-induced liver fibrosis through modulating gut microbiota and inhibiting the inflammatory response in liver.

[Study on the effect of integrated traditional Chinese and western medicine in the treatment of brucellosis].

Objective: To observe the clinical effect of integrated traditional Chinese and western medicine on brucellosis and its influence on humoral immune indexes. Methods: In October 2019, 169 cases of brucellosis hospitalized in Tianjin Second People's Hospital were selected as the research objects, and divided into two groups according to the random number method, 84 cases in the integrated treatment group and 85 cases in the western medicine treatment group. The western medicine treatment group was given antibiotics and other routine western medicine support treatment. The integrated treatment group was given traditional Chinese medicine for treatment based on syndrome differentiation, on the basis of western medicine treatment group, and 6 weeks was a course of treatment. The clinical efficacy and Traditional Chinese Medicine (TCM) syndrome scores were compared between the two groups of patients after treatment, and the changes in humoral immune indexes, biochemical, and liver and kidney functions of the patients before and after treatment were analyzed. Results: The total effective rate was 100.00% (84/84) in the integrated treatment group and 97.65% (83/85) in the western medicine treatment group. The difference was not statistically significant (P>0.05) . The difference was not statistically significant (P>0.05) . There was no statistically significant difference in TCM syndrome scores between the two groups before treatment (P>0.05) , and the TCM syndrome scores after treatment were lower than before treatment (P<0.05) . Among them, the TCM syndrome scores of the integrated treatment group were lower than those of the western medicine treatment group (P<0.05) . There was no significant difference in IgG, IgA, IgM, C3, C4, miRNA-155, C-reactive protein (CRP) , erythrocyte sedimention rate (ESR) , alanine aminotransferase (ALT) and aspartate aminotransferase (AST) between the two groups before treatment (P>0.05) . After treatment, IgG, IgA, IgM, miRNA-155, CRP, ESR, ALT and AST were all lower than before treatment, and C3 and C4 complement levels were higher than before treatment (P<0.05) . Among them, IgG, IgA, IgM, miRNA-155, CRP, ESR, ALT and AST in the integrative treatment group were all lower than the western medicine treatment group, while the C3 and C4 complement levels were higher than the western medicine treatment group (P<0.05) . Conclusion: The treatment of brucellosis with integrated traditional Chinese and western medicine can significantly improve the TCM syndrome score and reduce the levels of CRP and ESR. The mechanism of action may be related to the regulation of the patient's humoral immunological indicators.

E2F1-induced upregulation of lncRNA HCG18 stimulates proliferation and migration in gastric cancer by binding to miR-197-3p.

OBJECTIVE: LncRNA HCG18 is considered to be an oncogene in many types of tumors. The aim of this study was to explore the role of lncRNA HCG18 in gastric cancer (GC). PATIENTS AND METHODS: HCG18 levels in GC tissues were detected. Potential biological influences of HCG18 on GC cell phenotypes were examined by Cell Counting Kit-8 (CCK-8), wound healing and transwell assay. Subsequently, bioinformatics analysis, Chromatin immunoprecipitation (ChIP), Luciferase assay and rescue experiments were conducted to identify the regulatory network of HCG18 in GC. RESULTS: It was found that HCG18 was upregulated in GC samples, and the knockdown of HCG18 inhibited proliferative and migratory abilities in GC. The transcription factor E2F1 could directly bind to the promoter region of HCG18 and thus activate its transcription. In addition, HCG18 sponged miR-197-3p to stimulate the malignant development of GC. CONCLUSIONS: HCG18 is upregulated in GC samples by E2F1 induction, which stimulates proliferative and migratory abilities in GC by binding to miR-197-3p.

LncRNA AB073614 promotes the proliferation and inhibits apoptosis of cervical cancer cells by repressing RBM5.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "LncRNA AB073614 promotes the proliferation and inhibits apoptosis of cervical cancer cells by repressing RBM5, by L.-Y. Guo, C.-F. Qin, H.-X. Zou, M.-Y. Song, M.-L. Gong, C. Chen, published in Eur Rev Med Pharmacol Sci 2019; 23 (6): 2374-2379-DOI: 10.26355/eurrev_201903_17382-PMID: 30964162" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17382.

Transmission risk of infectious droplets in physical spreading process at different times: A review.

Droplets provide a well-known transmission media in the COVID-19 epidemic, and the particle size is closely related to the classification of the transmission route. However, the term "aerosol" covers most particle sizes of suspended particulates because of information asymmetry in different disciplines, which may lead to misunderstandings in the selection of epidemic prevention and control strategies for the public. In this review, the time when these droplets are exhaled by a patient was taken as the initial time. Then, all available viral loads and numerical distribution of the exhaled droplets was analyzed, and the evaporation model of droplets in the air was combined with the deposition model of droplet nuclei in the respiratory tract. Lastly, the perspective that physical spread affects the transmission risk of different size droplets at different times was summarized for the first time. The results showed that although the distribution of exhaled droplets was dominated by small droplets, droplet volume was proportional to the third power of particle diameter, meaning that the viral load of a 100 µm droplet was approximately 106 times that of a 1 µm droplet at the initial time. Furthermore, the exhaled droplets are affected by heat and mass transfer of evaporation, water fraction, salt concentration, and acid-base balance (the water fraction > 98%), which lead them to change rapidly, and the viral survival condition also deteriorates dramatically. The time required for the initial diameter (do) of a droplet to shrink to the equilibrium diameter (de, about 30% of do) is approximately proportional to the second power of the particle diameter, taking only a few milliseconds for a 1 µm droplet but hundreds of milliseconds for a 10 µm droplet; in other words, the viruses carried by the large droplets can be preserved as much as possible. Finally, the infectious droplet nuclei maybe inhaled by the susceptible population through different and random contact routes, and the droplet nuclei with larger de decompose more easily into tiny particles on account of the accelerated collision in a complex airway, which can be deposited in the higher risk alveolar region. During disease transmission, the infectious droplet particle size varies widely, and the transmission risk varies significantly at different time nodes; therefore, the fuzzy term "aerosol" is not conducive to analyzing disease exposure risk. Recommendations for epidemic prevention and control strategies are: 1) Large droplets are the main conflict in disease transmission; thus, even if they are blocked by a homemade mask initially, it significantly contains the epidemic. 2) The early phase of contact, such as close-contact and short-range transmission, has the highest infection risk; therefore, social distancing can effectively keep the susceptible population from inhaling active viruses. 3) The risk of the fomite route depends on the time in contact with infectious viruses; thus, it is important to promote good health habits (including frequent hand washing, no-eye rubbing, coughing etiquette, normalization of surface cleaning), although blind and excessive disinfection measures are not advisable. 4) Compared with the large droplets, the small droplets have larger numbers but carry fewer viruses and are more prone to die through evaporation.

[Clinical characteristics and next generation sequencing of three cases of Listeria monocytogenes meningitis with complications].

Objective: To summarize the clinical characteristics of Listeria monocytogenes meningitis (LMM) with complications, and analyze the outcomes of next generation sequencing. Methods: Clinical characteristics, laboratory findings, imaging features, antibiotics treatment, and next generation sequencing of cerebrospinal fluid were analyzed in 3 LMM patients who were hospitalized in the Department of Infectious Diseases of Beijing Children's Hospital Affiliated to Capital Medical University from July 2015 to November 2017. Results: The three patients were 1-year-old girl, 2-year-old girl, and 9-year-old boy, with normal immune function. They had eaten refrigerated food, milk or dairy products before onset. Symptoms included fever, headache, abdominal pain, diarrhea, vomiting, and convulsions, etc. The complications of two cases (case 2 and 3) were appendicitis and Meckel's diverticulitis. The other one (case 1) was with sepsis and pneumonia. Leukocyte counts in cerebrospinal fluid were elevated in all the three cases, and cranial magnetic resonance imaging showed meningeal or periventricular involvement. All the children were diagnosed with LMM by positive CSF culture. CSF for next generation sequencing was sent after carbapenem antibiotics using, yet all the results were positive. The positive results were returned 2, 9, and 9 days earlier than culture results, respectively. The gene coverage was 5.00%, 7.00%, 0.04%, and the reads was 2 561, 1 011 and 8, respectively. All the three children had recurrent fever despite using cephalosporin. Levels of leukocytes in the blood and CSF further elevated. After using carbapenem antibiotics, patients improved eventually and were discharged from hospital. Conclusions: LMM can occur in children with normal immune function and is usually associated with digestive system symptoms. Listeria monocytogenes can be detected quickly and accurately by the next generation sequencing technology, without being limited to sampling time and antibiotics application.

LncRNA AB073614 promotes the proliferation and inhibits apoptosis of cervical cancer cells by repressing RBM5.

OBJECTIVE: Recent studies have determined the crucial role of long noncoding RNAs (lncRNAs) in cancer development. Cervical cancer (CC) is a common type of fatal gynecological cancer worldwide. This study aims to identify the role of lncRNA AB073614 in the progression of CC. PATIENTS AND METHODS: Relative level of AB073614 in 3 CC cell lines and 48 paired CC samples was determined by the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The potential regulatory effects of AB073614 on the cellular behaviors of CC cells were explored through apoptosis assay, colony formation assay, and proliferation assay in vitro. The underlying mechanism of AB073614 in mediating the progression of CC was also conducted. RESULTS: The AB073614 expression was remarkably higher in CC tissues than that in adjacent tissues. The knockdown of AB073614 inhibited proliferation but induced apoptosis of CC cells. In addition, RBM5 (RNA binding motif 5) was upregulated in CC cells after knockdown of AB073614 in vitro. Furthermore, a negative correlation was seen between the expressions of RBM5 and AB073614 in CC tissues. CONCLUSIONS: AB073614 could promote proliferation and inhibit apoptosis of CC cells through downregulating RBM5, which may offer a new therapeutic intervention for CC patients.

[Artesunate attenuate chronic graft-versus-host disease by regulating Th17/Treg balance].

Objective: To investigate the effects of artesunate treatment on chronic graft-versus-host disease (cGVHD). Methods: Recipient BALB/c mice received 8 × 10(6) bone marrow cells with 8×10(6) spleen cells from B10D2 mice. Artesunate solubilized in acetone was injected intraperitoneally every day at the dose of 1 mg/kg at Day 28 after BMT. The clinical scores, survival and histopathological damage were analyzed. The frequency of Th17 and Tregs in PB and spleens from the mice were evaluated by flow cytometry. In addition, CD4(+) T cells from the spleens of mice were cultured in vitro, then stimulated with artesunate, the frequency of Th17 and Tregs in these splenocytes were evaluated by flow cytometry. Results: Artesunate administration diminished clinical and histopathological damage, and improved the survival of cGVHD mice[(46.57±7.83)% vs (55.71±6.99)%, χ(2)=5.457, P=0.020]; Artesunate contributed to Tregs development [(4.45±0.04)% vs (8.40±0.23)%, t=15.679, P<0.001; (6.62±0.24)% vs (10.48±0.48)%, t=6.587, P=0.003] while decreased Th17 cells [(1.51±0.18)% vs (0.58±0.19)%, t=7.233, P<0.001; (1.48±0.38)% vs (0.71±0.18)%, t=3.653, P=0.011] expressions in both PB and spleens, and decreased the Th17/Treg ratio (0.34±0.05 vs 0.09±0.03, t=7.621, P=0.002; 0.19±0.03 vs 0.06±0.02, t=6.993, P=0.002). Moreover, artesunate suppressed the Th17 cells expressions [(0.82±0.37) % vs (3.39±1.22) %, t=4.044, P=0.007] and contributed to Tregs development [(34.63±1.29) % vs (14.28±1.69) %, t=19.119, P<0.001], and also decreased the Th17/Treg ratio (0.24±0.09 vs 0.02±0.01, t=4.780, P=0.003) in vitro. Conclusions: Artesunate suppressed the Th17 cells expressions and contributed to Tregs development, which provided new sights into the development of a novel drug for cGVHD, e.g., artemisinin.

[Preparation and evaluation of blank and doxorubicin loaded poly (acrylic acid) microspheres for embolization].

OBJECTIVE: To prepare ion exchange doxorubicin-loaded poly (acrylic acid) microspheres (DPMs) and evaluate the properties of these chemoembolic agents. METHODS: Poly (acrylic acid) microspheres (PMs) without drug were prepared by inverse suspension polymerization method and then doxorubicin was loaded by ion exchange mechanism to prepare DPMs. Optical microscope was used to investigate the morphology and particle size distribution of PMs and DPMs; fluorescence microscope and confocal microscope were used to observe the distribution of doxorubicin after drug loading. Elasticities of both the microspheres were evaluated by texture analyzer. High performance liquid chromatography (HPLC) method was established to determine the drug loading behavior of PMs and releasing behavior of DPMs. The in vivo embolic property was evaluated by embolizing the hepatic artery of a rabbit with 0.1 mL of DPMs. RESULTS: PMs and DPMs were both spherical in shape, smooth in surface and dispersed well. Doxorubicin was mainly in the outer area inside of DPMs and distributed evenly. The average particle size of PMs and DPMs were (283±136) µm and (248±149) µm, respectively. PMs and DPMs both had good compression ability with the Young's modulus of (62.63±1.65) kPa and (93.94±1.10) kPa separately. PMs reached the drug loading balance at 12 h, and the entrapment efficiency was greater than 99%. Drug loading of PMs in doxorubicin solution at the concentration of 5.0 g/L and 12.5 g/L was (19.78±0.27) g/L and (49.45±0.37) g/L, respectively. Doxorubicin released slowly from DPMs in PBS and the accumulative release percentages of DPMs with corresponding drug loading were 6.82%±0.02% and 2.83%±0.10% after 24 h, respectively. Arterial angiograms showed that the hepatic artery of the rabbit was successfully embolized with DPMs. CONCLUSION: DPMs with good performance of loading doxorubicin could be a potential embolic agent for transcatheter arterial chemoembolization.

Effects of different feed type exposure in early life on performance, rumen fermentation, and feed preference of dairy calves.

The aim of the study was to evaluate the effects of early feed exposure (EFE) to different feedstuffs in dairy calves on feed preference once fed a free-choice diet and a total mixed ration later in life. Thirty (30) female Holstein calves were randomly assigned at birth to 1 of 3 EFE treatments-concentrate only (CON), hay only (HO), and concentrate and hay (COH)-from d 2 to 56. After that, all calves were offered both concentrate and hay in different buckets from d 57 to 70 to allow them free choice between the 2 feedstuffs. Calves were then transferred to a heifer barn, housed within treatment in pairs (2 calves/pen), and fed TMR from d 71 to 196. Feed intake was recorded daily from d 2 to 70 to determine the feed preference before and after weaning. Fresh TMR and orts were collected daily in the last week of the experiment (d 190 to 196) for analysis of feed sorting and intake. Body weight and structural growth were recorded at d 1, 28, 56, 70, and 190. Blood for determining glucose and rumen fluid for determining ruminal pH and volatile fatty acids concentrations were sampled on d 28, 56, 70, and 190. Early feed exposure did not affect feed intake, body weight, average daily gain, blood glucose, and structural growth before and after weaning but did affect feed preference and rumen fermentation. After transition to a free-choice diet, HO calves consumed more hay (550.2 g/d) than CON (177.4 g/d) and COH (396.4 g/d) calves on the first day only. However, COH calves consumed a greater amount of hay, resulting in a higher ratio of hay to total solids compared with either CON or HO calves during d 57 to 70. Upon transition to a TMR, a similar sorting pattern was exhibited between treatments, with calves sorting against the long and for the fine particle fractions. Although no significant long-term effects of different EFE on rumen pH, volatile fatty acids, and blood glucose persisted at wk 27 (from d 190 to 196), calves exposed to COH early had an improved ability to sort for long feed particles compared with CON and HO calves later in life. Our results suggest that EFE could influence choice of feed immediately after weaning and may have long-lasting effects on feed preference in heifers later in life. Further studies with more calves are recommended.

[Relationship between gestational glucose, lipid metabolism parameters and fetal distress].

OBJECTIVE: To study the relationship between gestational glucose, lipid metabolism parameters and fetal distress. METHODS: Retrospectively, 82 cases of primipara with fetal distress and 246 cases of primipara without any obstetric complications were analyzed. The latter were treated as control group. All the patients were from the same hospital between January, 2014 and January, 2016. Factors as fasting plasma-glucose (FPG), triglyceride (TG), total cholesterol (TC),high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) parameters during early pregnancy, blood glucose of fasting, 1 hour and 2 hours in 75 g oral glucose tolerance test (OGTT), at 24 to 28 weeks of gestation, hemoglobin and blood pressure parameters during ante partum were recorded for all the cases while parameters as glucose and lipid, hemoglobin, blood pressure and cesarean section rate were compared between the 2 groups. RESULTS: FPG during early gestation, blood glucose of fasting, 1 hour and 2 hours 75 g OGTT during mid gestation, systolic blood pressure and diastolic blood pressure during late gestation in the'fetal distress'group were significantly higher than that of the control group. Hemoglobin during late gestation in the fetal distress group was lower than that of the control group, with statistically significant difference (P<0.05). The rate of cesarean section in the fetal distress group was higher than that in the control group (χ(2)=4.489, P=0.034). CONCLUSIONS: High BMI at pre-pregnancy, high blood glucose during early and mid-gestation, high blood pressure and anemia during late gestation were related to the fetal distress group. Cesarean section rate was high for pregnancy women with fetal distress.

Role of the nitrergic pathway in motor effects of oxytocin in rat proximal colon.

BACKGROUND: Oxytocin (OT) reduces rat duodenal tone and mouse intestinal transit; however, the underlying mechanisms are not totally understood. Consequently, this study was designed to investigate the influence of OT on spontaneous mechanical activity and neurally evoked responses, to characterize the mechanisms of the action, and to determine the distribution of the OT receptor (OTR) in rat proximal colonic muscle strips. METHODS: The organ bath technique with electrical field stimulation, western blotting, and immunofluorescence were used. KEY RESULTS: In rat proximal colon, exogenous OT induced a concentration-dependent reduction of the spontaneous mechanical activity without affecting the resting basal tone, which was abolished by atosiban, an OTR antagonist, by tetrodotoxin (TTX), a neural blocker or by Nω-propyl-l-arginine hydrochloride, an inhibitor of neuronal nitric oxide synthase (nNOS). The inhibitory effects of OT were not affected by atropine or the vasoactive intestinal peptide (VIP) receptor antagonist [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP (VIPHyb). Proximal colon responses to electrical field stimulation were characterized by nonadrenergic, noncholinergic (NANC) relaxation, which was followed by an off-contraction. Oxytocin enhanced only NANC relaxation. Oxytocin stimulated spontaneous NO release from the longitudinal muscle myenteric plexus preparation of rat proximal colon. Western blot and immunohistochemistry experiments showing the presence of the OTR in proximal colon, and its co-localization with nNOS established that myenteric nitrergic neurons express OTR. CONCLUSIONS & INFERENCES: The activation of OTR located on nitrergic neurons may negatively modulate colonic spontaneous contraction and enhance electrically evoked NANC relaxation through excitation of NO release.

Association between the expression of HIF-1α and VEGF and prognostic implications in primary liver cancer.

The goal of this study was to investigate the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in primary liver cancer (PLC) and their association with prognosis. Tumor tissue, non-tumor tissue, and blood samples of 75 PLC patients were collected. Blood samples of 20 volunteers were also collected as healthy controls. Real-time quantitative reverse transcription-polymerase chain reaction was used to analyze the mRNA levels of HIF-1α and VEGF in the tissues. Protein expression of HIF-1α and VEGF was analyzed by immunohistochemistry. Enzyme-linked immunosorbent assay was used to detect the expression of HIF-1α and VEGF at the serum level. Univariate tests, multivariate Cox proportional hazards model, and the Student t-test were used to analyze the data. HIF-1α and VEGF showed higher expression in PLC tumor tissue both at the mRNA and protein levels. HIF-1α and VEGF expression was positive in 62.67 and 66.67% of PLC patients, respectively. HIF-1α and VEGF expression was significantly related to tumor stage and lymph nodes and lung metastases (P < 0.05). HIF-1α expression correlated with VEGF expression in PLC (r = 0.665, P < 0.05). Both HIF-1α and VEGF were significantly associated with overall survival (P < 0.05), while HIF-1α was identified as an independent prognostic factor. Both HIF-1α and VEGF, as the predictors of efficacy of TACE and metastasis of PLC, are biomarkers indicating PLC in advanced stage, and implied poor prognosis in patients with PLC. HIF-1α and VEGF could potentially be targets to improve outcomes in PLC.