Effects of breast milk intake ratio during hospitalization on antibiotic therapy duration in preterm infants less than 34 gestational weeks: a multicenter retrospective cohort study / 中华围产医学杂志

Objective:To investigate the effects of breast milk to total milk intake ratio during hospitalization on the duration of antibiotic therapy in preterm infants less than 34 weeks of gestation.Methods:Clinical data of preterm infants ( n=1 792) less than 34 gestational weeks were retrospectively collected in 16 hospitals of Jiangsu Province Neonatal-Perinatal Cooperation Network from January 1, 2019, to December 31, 2021. The days of therapy (DOT) were used to evaluate the duration of antibiotic administration. The median DOT was 15.0 d (7.0-27.0 d). The patients were divided into four groups based on the quartiles of DOT: Q 1 (DOT≤7.0 d), Q 2 (7.0 d<DOT≤15.0 d), Q 3 (15.0 d<DOT≤27.0 d) and Q 4 (DOT>27.0 d) groups. According to the breast milk intake ratio (breast milk intake to total milk intake during hospitalization×100%), they were also divided into four groups: very-low-ratio breastfeeding group (breast milk intake ratio≤25%), low-ratio breastfeeding group (25%<breast milk intake ratio≤50%), medium-ratio breastfeeding group (50%<breast milk intake ratio≤75%) and high-ratio breastfeeding group (breast milk intake ratio>75%). Univariate analysis ( Chi-square test and Kruskal-Wallis rank-sum test) was used to analyze the factors influencing DOT. Spearman correlation analysis and trend Chi-square test were used to explore the relationship between breast milk intake ratio and DOT. After using multiple imputations to address missing data, two models were constructed after adjusting for different factors, and multinomial logistic regression model was applied to evaluate the effects of the breast milk intake ratio on DOT. Finally, sensitivity analysis was conducted to assess the stability of the models. Results:(1) Of the 1 792 preterm infants, there were 507 (28.3%) in the Q 1 group, 422 (23.5%) in the Q 2 group, 438 (24.4%) in the Q 3 group and 425 (23.7%) in the Q 4 group. (2) The median values of DOT in the very-low-ratio, low-ratio, medium-ratio and high-ratio breastfeeding groups were 20.0 d (11.0-31.0 d), 20.0 d (11.0-32.0 d), 13.0 d (6.0-25.8 d) and 10.0 d (4.0-21.0 d), respectively. Compared with the very-low-ratio and low-ratio breastfeeding groups, the medium-ratio and high-ratio breastfeeding groups had shorter DOT (all P<0.05). (3) After adjusting for factors with P<0.1 (prenatal glucocorticoid exposure, antimicrobial use within 24 h before delivery, gestational age at delivery, birth weight, Apgar score≤7 at 1 min, neonatal respiratory distress syndrome, infectious pneumonia and early-onset neonatal sepsis) between the DOT quartile groups, it showed that medium-ratio and high-ratio breastfeeding were protective factors in contrast to very-low-ratio breastfeeding in the Q 2, Q 3 and Q 4 groups as compared with the Q 1 group [Q 2 group: OR=0.50 (95% CI: 0.30-0.85) and OR=0.36 (95% CI: 0.26-0.51); Q 3 group: OR=0.31 (95% CI: 0.18-0.55) and OR=0.20 (95% CI: 0.14-0.29); Q 4 group: OR=0.22 (95% CI: 0.12-0.42) and OR=0.17 (95% CI: 0.12-0.26)]. Conclusion:Breast milk intake accounting for over 50% of total milk intake has a positive impact on reducing DOT in premature infants requiring antibiotics, which suggests that breastfeeding should be actively encouraged.

Research progress on probiotics and short-term clinical outcomes in extremely premature infants / 中国小儿急救医学

The extremely premature infants have different degrees of immature organ development, abnormal intestinal flora establishment and low immune function, and are prone to necrotizing enterocolitis, late-onset sepsis and other complications.Probiotics can improve intestinal flora, and regulate cell metabolic activity and immune function.Probiotics can be used to prevent necrotizing enterocolitis, and late-onset sepsis and so on.However, the possible harm of probiotics to extremely premature infants should not be ignored.This review summarized the effects of probiotics on extremely premature infants.

A qualitative study of experiences of non suicidal self injury in adolescents with depression / 中国学校卫生

Objective@#To understand the real experience and feelings of self injurious cutting in adolescents with depression, to provide guidance for clinical targeted interventions.@*Methods@#During November 2021 to May 2022, 19 adolescent patients with depression who had cut themselves as the type of non suicidal self injury were recruited from a tertiary first class psychiatric hospital in Chengdu, Sichuan Province. All the participants were interviewed in a semi structured manner, which used the interpretative phenomenological analysis to analyze the transcription data.@*Results@#The experience and feelings of non suicidal self injury in adolescent with depression could be summarized into five themes: self injury thoughts that arise under external interference; self injurious behavior in a thousand thoughts; painful but a happy experience of self injury; cutting as the most frequently selected form of non suicidal self injury; decreases in self injurious behavior reduced when they feel love and responsibility.@*Conclusion@#Non suicidal self injury of adolescent patients with depression are affected by various factors. Clinicians should provide targeted clinical care according to the characteristics of patients, as well as the no suicide contract, alternative skills of non suicidal self injury behaviors, and a multi dimensional social support platform with the families of patients.

Effect and Mechanism of Nongsuo Dangguiwan in Relieving Oxidative Stress in Premature Ovarian Insufficiency Rats Based on Nrf2/HO-1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of Nongsuo Dangguiwan in improving ovarian oxidative stress in rats with ovarian dysfunction. MethodThirty-six adult female SD rats were randomly divided into normal group， model group， positive drug group （Femoston， 0.3 mg·kg-1）， and high-， medium-， and low-dose groups of concentrated Nongsuo Dangguiwan （2.08， 4.16， 8.32 g·kg-1）， with six rats in each group. Rats， except for those in the normal group， were injected with 80 mg·kg-1 vinyl cyclohexene dioxide （VCD） per day for 14 consecutive days to induce ovarian dysfunction. From the 15th day， rats were treated with corresponding drugs by gavage， while those in the model group received 2 mL·kg-1 saline， once daily for 28 consecutive days. The ovarian index， levels of related hormones including estradiol （E2）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and anti-mullerian hormone （AMH） in serum， as well as superoxide dismutase （SOD） activity and glutathione （GSH） content in serum were measured by enzyme-linked immunosorbent assay （ELISA）. The malondialdehyde （MDA） content in serum was detected by the thiobarbituric acid （TAB） method. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. The expression of nuclear factor E2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， SOD2， and SOD1 in ovarian tissues was detected by immunohistochemistry （IHC） and Western blot. ResultCompared with the normal group， the model group showed a significant reduction in growing follicles in the ovary， loose arrangement of granulosa cells in the follicle， decreased body weight， ovarian index， and serum AMH and E2 levels， increased LH and FSH levels （P<0.01）， reduced levels of SOD and GSH in serum （P<0.01）， and increased MDA level （P<0.01）. Compared with the model group， the groups with drug intervention showed increased ovarian index （P<0.05， P<0.01）， increased serum E2 level （P<0.05， P<0.01）， decreased FSH， AMH， and LH levels （P<0.05， P<0.01）， increased number of growing follicles in the ovary， potentiated SOD activity in serum， increased GSH content， decreased MDA content （P<0.05， P<0.01）， and up-regulated expression levels of Nrf2， HO-1， SOD2， and SOD1 proteins in ovarian tissues （P<0.05， P<0.01）. ConclusionNongsuo Dangguiwan can regulate serum hormone levels， increase the expression of Nrf2， HO-1， SOD2， and SOD1 in ovarian tissues， and improve ovarian antioxidant capacity to resist oxidative stress injury， thereby improving ovarian reserve function.

Diagnosis and treatment of a child with alveolar capillary dysplasia with misalignment of pulmonary veins due to variant of FOXF1 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the diagnosis, treatment and genetic characteristics of a neonate with severe pulmonary hypertension and respiratory failure.@*METHODS@#Perinatal history, clinical manifestations, laboratory finding and diagnosis and treatment data of the child were collected. Whole exome sequencing was carried out for the child, and Sanger sequencing was used to verify the candidate variants.@*RESULTS@#The female neonate has developed progressive respiratory failure and refractory pulmonary hypertension shortly after birth. Conventional treatment such as mechanical ventilation, vasoactive drugs, and inhaled nitric oxide were ineffective. She has developed sustained pulmonary hypertension after weaning from extracorporeal membrane oxygenation therapy, and had died after the treatment had ceased. Whole exome sequencing revealed that she has harbored a heterozygous de novo variant of c.682_683insGCGGCGGC (p.G234Rfs*148) of the FOXF1 gene, which was predicted as pathogenic based on guidelines from the American College of Medical Genetics and Genomics (ACMG), with evidence items of PVS1_Strong+PM2_Supporting+PS2. Based on her clinical manifestations and result of genetic testing, the child was diagnosed with alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV).@*CONCLUSION@#Discovery of the c.682_683insGCGGCGGC (p.G234 Rfs*148) variant of the FOXF1 gene has expanded the mutational spectrum of the FOXF1 gene, which has facilitated implementation of specific treatment and provided a basis for clinical diagnosis and genetic counseling.

Risk factors of bronchopulmonary dysplasia in very preterm infants: a national multicenter study / 中国小儿急救医学

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

Effect of Jianpi Yishen Huazhuo Prescription on Ovarian Function in Rats with Polycystic Ovary Syndrome Based on NLRP3 Inflammatory Pathway / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Jianpi Yishen Huazhuo prescription in the improvement of ovarian function in polycystic ovary syndrome （PCOS）. MethodSeventy female SD rats in SPF grade were randomly divided into 6 groups， 15 in the blank group and 15 in the model group， 10 in the metformin group （0.1 g·kg-1·d-1）， and 10 in the low （1.275 g·kg-1·d-1）， medium （2.55 g·kg-1·d-1）， and high-dose （5.10 g·kg-1·d-1） Jianpi Yishen Huazhuo prescription groups. The blank group was given normal saline （10 mL·kg-1·d-1） by gavage and ordinary feed， and the other groups were given letrozole （1 mg·kg-1·d-1） by gavage combined with high-fat feed for 21 days to induce the model of PCOS. After modeling， the blank group and model group were given equal volume normal saline by gavage， and each drug group was given the corresponding dose of the drug by gavage for 30 days. The changes in body mass and fasting blood glucose （FPG） of rats before and after modeling were compared. Hematoxylin eosin （HE） staining was used to observe the morphological change in the ovaries of rats in each group. The serum levels of follicle stimulating hormone （FSH）， luteinizing hormone （LH）， testosterone （T）， anti-Mullerian hormone （AMH）， and estradiol （E2） were measured by enzyme-linked immunosorbent assay （ELISA）， and the LH/FSH ratio was calculated. Immunohistochemical staining （IHC） and Western blot were used to detect the protein expression levels of nucleoside binding oligomerization domain protein like receptor 3 （NALP3）， apoptosis-associated speck-like protein （ASC）， cysteine protease-1 （Caspase-1）， nuclear transcription factor-κB （NF-κB）， interleukin-1β （IL-1β）， interleukin-18 （IL-18）， and interleukin-6 （IL-6） in the rat ovaries. ResultAs compared with the blank group， large follicles with polycystic expansion were found in the ovaries of the model group， no dominant follicles were found， the granular layer of follicles decreased and arranged loosely， and the number of corpus luteum decreased significantly. Serum T， LH， AMH and LH/FSH increased in the model group （P<0.05， P<0.01）， while FSH and E2 decreased （P<0.05， P<0.01）. The relative protein expression levels of NALP3， ASC， Caspase-1， NF-κB， IL-1β， IL-18， and IL-6 increased （P<0.05， P<0.01） in the ovaries of the model group. Compared with the model group， the low， medium， and high-dose Jianpi Yishen Huazhuo prescription groups and the metformin group showed growing follicles and corpus luteum at all levels， the number of cystic expanding follicles decreased， the thickness of follicular granular layer increased， the number of follicular fluid increased， mature follicles were visible， and the local morphology of oocytes was complete. Serum T， LH， AMH， and LH/FSH in these groups decreased （P<0.05， P<0.01）， while E2 and FSH increased （P<0.05）. The relative protein expressions of NALP3， ASC， Caspase-1， NF-κB， IL-1β， IL-18， and IL-6 in the ovaries of these groups decreased （P<0.05， P<0.01）. There was no significant difference among the treatment groups. ConclusionBy inhibiting the activation of NLRP3 inflammasome， Jianpi Yishen Huazhuo prescription reduces the release of NALP3， ASC， Caspase-1， NF-κB， IL-18， IL-1β， and IL-6 inflammatory factors in ovarian tissues， regulates endocrine level， and effectively reduces PCOS inflammatory statu， so as to play a role in improving ovarian function.

Status of health-promoting lifestyle and influencing factors for caregivers of children with neurodevelopmental disorders / 中华行为医学与脑科学杂志

Objective:To describe the health-promoting lifestyle of caregivers of children with neurodevelopmental disorders and analyze its influencing factors.Methods:A total of 352 caregivers of children with neurodevelopmental disorders in a hospital in Shenzhen were investigated by questionnaire.The main caregivers were investigated with health-promotion lifestyle scale Ⅱ.Generalized linear model was used to analyze the influencing factors of the health promoting lifestyle score of the caregivers by SPSS 20.0 and R 3.6.0 softwares.Results:The total score of health promotion lifestyle for caregivers of children with neurodevelopmental disorders was (127.66±17.87). The standardized score was (62.05±8.96), with the highest standardized score being (69.62±11.04) for the nutrition dimension and the lowest score being (51.67±11.45) for the physical activity dimension.The difference between the groups was statistically significant ( F=62.780, P<0.01). The results of linear regression analysis showed that the education level ( "junior college" vs "primary and junior high school" : β=14.524, t=3.054, P=0.002; "undergraduate and above" vs "primary and junior high school" : β=18.561, t=3.936, P<0.001), care time ( ">3 years" vs " <1 year" : β=-7.156, t=-3.687, P=0.003), and family income ( "10 000-20 000 yuan/ month" vs "<5 000 yuan/month" : β=14.351, t=3.050, P=0.002) were the influencing factors of health promotion lifestyle of caregivers. Conclusion:The life style of caregivers should be paid attention to.It is necessary to help them improve their health-promoting lifestyle through multiform health promotion methods.

The level and clinical value of fecal calprotectin in very low birth weight infants / 中国小儿急救医学

Objective:To understand the change trend and influencing factors of fecal calprotectin(FC) in very low birth weight(VLBW) infants, and to explore the application value of FC detection in the diagnosis of necrotizing enterocolitis(NEC) in VLBW infants.Methods:VLBW infants hospitalized in the neonatal department at Quanzhou Children′s Hospital from June 2018 to May 2019 were selected as research object for a prospective study.Fecal samples from the 1st, 7th, 14th, 21st, 28th and 35th days after birth and fecal samples from the acute and recovery stages of NEC were collected continuously.The content of FC was determined quantitatively by immunofluorescence assay.Results:(1) The FC level of non NEC VLBW infants from 1 to 35 days after birth was 143.5(47.8, 391.2) μg/g.Univariate analysis showed that the level of FC fluctuated with the postnatal age, the level of FC was the highest at 21 days, and then decreased.The level of FC increased significantly in formula feeding, premature rupture of membranes, neonatal sepsis, feeding intolerance and pregnant mothers without glucocorticoid before delivery( P< 0.05). (2) Multivariate covariance analysis showed that prenatal application of glucocorticoid( F=10.550, P=0.001), premature rupture of membranes( F=13.311, P<0.001), neonatal sepsis( F=8.001, P=0.005), feeding intolerance( F=4.751, P=0.030) and NEC( F=54.566, P<0.001) had significant effects on FC level.After controlling the effects of prenatal corticosteroid, premature rupture of membranes, neonatal sepsis and feeding intolerance, the levels of FC in NEC group and non-NEC group were 3 162.3(1 412.5-7 244.4)μg/g and 141.3(125.9-162.2)μg/g, respectively.In NEC group, the levels of FC in acute stage and recovery stage were 3 166.9(1 745.1, 6 806.4)μg/g and 130.9(97.4, 273.9)μg/g, respectively, with significant difference( t=10.304, P<0.001). While the levels of FC were 2 347.9(1 404.4, 5 893.4)μg/g in the mild NEC and 4 114.7(2 764.5, 9 208.4)μg/g in the moderate or severe NEC, respectively, with no significant difference( t=1.131, P=0.280). Conclusion:The levels of FC fluctuate with postnatal age and it is affected by multiple factors.FC maybe a useful marker for the diagnosis and evaluation of efficacy of NEC in VLBW infants.

Effects of targeted silencing of PRL-3 gene on proliferation, migration, invasion and epithelial-mesenchymal transition of lung cancer cells / 国际肿瘤学杂志

Objective:To observe the effects of lentivirus-mediated shRNA silencing of PRL-3 gene on the proliferation, migration and invasion of lung cancer A549 cells and regulation of epithelial-mesenchymal transition (EMT) signaling pathway.Methods:Lung cancer A549 cells were transfected with lentiviral interference vector carrying PRL-3 shRNA to build a stable PRL-3-silencing cell line. The cells were divided into blank control group, NC shRNA group (negative control group) and PRL-3 shRNA group (PRL-3 inhibiting RNAi lentivirus group). CCK-8 method, colony formation assay, Transwell and invasion chamber assay were performed to detect the proliferation, migration and invasion ability of A549 cells respectively. The expressions of E-cadherin and Snail mRNA were detected by real-time fluorescent quantitative PCR.Results:The stable PRL-3-silencing cell line was successfully constructed. The knockdown efficiency of PRL-3 gene in the PRL-3 shRNA group reached 83.5%. CCK-8 method detected the proliferation ability of A549 cells, and the results showed the 24 h absorbance ( A) values of A549 cells in the blank control group, NC shRNA group and PRL-3 shRNA group were 0.296±0.008, 0.342±0.007 and 0.292±0.004, with a statistically significant diffe-rence ( F=106.300, P<0.001), and the PRL-3 shRNA group was significantly lower than the NC shRNA group ( P<0.001); at 48, 72, 96 h after transfection, the cell proliferation abilities of the PRL-3 shRNA group were also significantly inhibited. Colony formation assay showed that the numbers of colony formation in the blank control group, NC shRNA group and PRL-3 shRNA group were 166.7± 6.7, 158.0±6.1 and 119.7±1.5 ( F=67.290, P<0.001). The ability of colony formation of the PRL-3 shRNA group was significantly lower than that of the NC shRNA group ( P<0.001). The numbers of migrated cells in the blank control group, NC shRNA group and PRL-3 shRNA group were 100.0±1.9, 98.8±1.9 and 44.6±7.6 ( F=430.300, P<0.001). The migration ability of the PRL-3 shRNA group was significantly lower than that of the NC shRNA group ( P<0.001). The numbers of invaded cells in the three groups were 117.7±4.1, 113.1±6.6 and 55.6±8.4 ( F=247.200, P<0.001). The invasion ability of the PRL-3shRNA group was significantly lower than that of the NC shRNA group ( P<0.001). Real-time fluorescent quantitative PCR detection results showed that after silencing the expression of PRL-3, the relative expression level of E-cadherin mRNA in A549 cells was significantly up-regulated, and the level of Snail mRNA was significantly down-regulated. Conclusion:PRL-3 silencing can inhibit the proliferation, migration and invasion of A549 cells effectively. PRL-3 may affect the invasion of lung cancer cells through the EMT pathway.

Formulation of a rational dosage regimen of ceftiofur hydrochloride oily suspension by pharmacokineticpharmacodynamic (PK-PD) model for treatment of swine Streptococcus suis infection

Background@#Our previously prepared ceftiofur (CEF) hydrochloride oily suspension shows potential wide applications for controlling swine Streptococcus suis infections, while the irrational dose has not been formulated. @*Objectives@#The rational dose regimens of CEF oily suspension against S. suis were systematically studied using a pharmacokinetic-pharmacodynamic model method. @*Methods@#The healthy and infected pigs were intramuscularly administered CEF hydrochloride oily suspension at a single dose of 5 mg/kg, and then the plasma and pulmonary epithelial lining fluid (PELF) were collected at different times. The minimum inhibitory concentration (MIC), minimal bactericidal concentration, mutant prevention concentration (MPC), post-antibiotic effect (PAE), and time-killing curves were determined. Subsequently, the area under the curve by the MIC (AUC 0–24h /MIC) values of desfuroylceftiofur (DFC) in the PELF was obtained by integrating in vivo pharmacokinetic data of the infected pigs and ex vivo pharmacodynamic data using the sigmoid E max (Hill) equation. The dose was calculated based on the AUC 0–24h /MIC values for bacteriostatic action, bactericidal action, and bacterial elimination. @*Results@#The peak concentration, the area under the concentration-time curve, and the time to peak for PELF's DFC were 24.76 ± 0.92 µg/mL, 811.99 ± 54.70 μg·h/mL, and 8.00 h in healthy pigs, and 33.04 ± 0.99 µg/mL, 735.85 ± 26.20 μg·h/mL, and 8.00 h in infected pigs, respectively. The MIC of PELF's DFC against S. suis strain was 0.25 µg/mL. There was strong concentration-dependent activity as determined by MPC, PAE, and the time-killing curves. The AUC 0–24h /MIC values of PELF's DFC for bacteriostatic activity, bactericidal activity, and virtual eradication of bacteria were 6.54 h, 9.69 h, and 11.49 h, respectively. Thus, a dosage regimen of 1.94 mg/kg every 72 h could be sufficient to reach bactericidal activity. @*Conclusions@#A rational dosage regimen was recommended, and it could assist in increasing the treatment effectiveness of CEF hydrochloride oily suspension against S. suis infections.

Analysis of the utilization of antibacterial drugs in 100 cases of old community-acquired pneumonia with chronic obstructive pulmonary disease / 中国基层医药

Objective To investigate the utilization of antibacterial drugs in the old community-acquired pneumonia (CAP) with chronic obstructive pulmonary disease(COPD) in our hospital.To analyze the rational application of antibacterial drugs,thus to provide a powerful reference for clinical diagnosis and treatment.Methods From June 2011 to June 2013,100 patients with COPD and CAP were selected in Xiaolan People's Hospital.The average age was (76.95 ±6.57) years old,including 62 males and 38 females.The utilization of antibacterial drugs was investigated by retrospective study in the patients.Results In the course of treatment,the rate of using the antibacterial drugs in 100 patients was 100％,concerning 13 varieties of 5 major categories,including β-lactam (including β-lactam/β-lactamase inhibitors),quinolones,carbapenems,macrolides,aminoglycosides.The largest frequency was piperacillin/sulbactam,up to 92.Ceftezole,cefotian and azithromycin were less than 0.9 for DUI in DDDS ordering 10 drugs,it showed that the frequency was insufficient or the dosage was too small.For example,insufficient frequency of cephalosporin once a day and small dosage of azithromycin 0.25g once a day.Combination with two kinds of antimicrobial drugs was common,it was relatively rational between the combination of drugs,usually cephalosporins + quinolones,β-lactam/β-lactamase inhibitors + quinolones,β-lactam/β-lactamase inhibitors + macrolides.Conclusion The etiology of 100 elderly patients with COPD and CAP in our hospital is mainly Gram-negative bacteria.The anti-infection treatment is mainly cefdiazine and piperacillin/sulbactam,and the combined drug was mainly quinolones.The drug regimen and treatment course are reasonable,there is a high prognosis in the patients.

Intestinal fatty acid-binding protein expression in the intestinal tissue and clinical significance in neonatal rats with necrotizing enterocolitis / 中国新生儿科杂志

Objective To study the expression of intestinal intestinal fatty acid-binding protein (I-FABP) and its clinical significance in an experimental model of necrotizing enterocolitis (NEC) in neonatal rats. Method Twenty-four neonatal Sprague-Dawley (SD) rats were randomly assigned into 4 groups at 48 h after birth (6 rats in each group):group A (control group), group B (NEC group-1), group C (NEC group-2), and group D (NEC group-3). The neonatal rats were fed by the mother rats in the same cage within 48 h after birth. After 48 h, the NEC group received artificial feeding, hypoxia, cold stimulation and lipopolysaccharide (LPS) gavage (10 mg/kg). NEC group-1, 2 and 3 were sacrificed on an empty stomach at 1, 2 and 3 d after the modeling. The control group was sacrificed on an empty stomach 3 d after the modeling without special treatment. Intestinal tissue were obtained from each rats. The histological changes of ileal tissues were studied using hematoxylin-eosin (HE) staining. The expressions of intestinal I-FABP were detected using RT-PCR and ELISA methods. Result Compared with the control group, body weight of rats in NEC group-1, 2 and 3 were lower, and pathology scores in these three groups were higher (P<0.05). The levels of intestinal I-FABP mRNA in NEC group-1, NEC group-2 and NEC group-3 were 2.69±0.27, 2.12±0.09, 3.18± 0.22, respectively. The protein expression levels were 363.7 ± 11.4, 321.7 ± 45.8, 432.3 ± 50.3, respectively. The mRNA and protein levels were all significantly higher than the control group (mRNA: 1.00 ± 0.02, protein: 134.2 ± 24.0, P<0.05). Conclusion I-FABP was a useful marker for ischemic injury to the intestine. These findings may contribute to a better diagnosis of NEC in newborns.

Clinical effects of continuous blood purification in the treatment of newborns with severe sepsis and multiple organ dysfunction syndrome / 中国新生儿科杂志

Objective To study the clinical effects of continuous blood purification (CBP) in the treatment of newborns with severe sepsis and multiple organ dysfunction syndrome (MODS). Method From May 2013 to November 2018, the clinical data of infants with severe sepsis and MODS receiving CBP in the neonatal department of our hospital were retrospectively analysed. Changes of blood pressure, arterial partial pressure of oxygen/inhaled oxygen concentration (PaO2/FiO2), pH, serum potassium, sodium, urea nitrogen, creatinine, urine volume and maintenance dose of adrenaline at different time points before and after CBP were analysed. Result According to the inclusion and exclusion criteria, a total of 8 newborns with sepsis and MODS were enrolled in the study. One patient had the complication of perforated colon, and the other one had acute renal failure. The number of affected organs in these infants was 3～5. Six cases began CBP treatment within 1～5 days after admission, and the other two cases began CBP treatment on the 38th and 47th days after admission. The average treatment duration was (58.6±25.9) h. The effective rate of CBP in the treatment of severe sepsis with MODS was 75.0％(6/8). Blood pressure was increased at 6 h, 12 h, 24 h and 48 h after treatment and at the end of treatment. PaO2/FiO2 and blood pH were increased. The urine volume was increased at 24 h and 48 h after treatment and at the end of treatment (P<0.05). Serum potassium, urea nitrogen and creatinine were significantly decreased (P<0.05). The maintenance dose of adrenaline was also decreased significantly at 12 h after CBP (P<0.05), and withdrawn at 48 h after treatment. Only one case experienced membrane blockage during CBP. Dialysis was continued after the replacement of filtration membrane. No other complications existed. Conclusion CBP is effective in the treatment of neonatal severe sepsis with MODS. It can improve the circulation and renal function.

Application of amplitude integrated electroencephalography in cerebral function monitoring in preterm infants younger than 30 weeks of gestation / 中国小儿急救医学

Objective To explore the value of amplitude integrated electroencephalography (aEEG) in cerebral function monitoring in preterm infants younger than 30 weeks of gestation. Methods A total of 165 cases of preterm infants younger than 30 weeks of gestation were prospectively enrolled in the study from September 2015 to February 2017,including 20 preterm infants with severe brain injury ( severe brain injury group) and 145 with non-severe brain injury ( non-severe brain injury group). Five aspects of each tracing, such as continuity(Co),sleep-wake cycling( Cy),amplitude of the lower border(LB),bandwidth( B) and total maturation scores,were evaluated and compared between two groups by applying a preterm infants aEEG scoring system. The neuromotor development of preterm infants survivors was assessed by using the 0 to 6 years old children′s neurological and psychological development scale of China Capital Institute of Pediatrics. Clinical data were collected and compared with the results of aEEG. Results The scores for Co,Cy,LB,B as well as total maturation scores of preterm infants with severe brain injury at different gestational age were lower than those of infants with non-severe brain injury at the same gestational age. The differences were sta-tistically significant (all P<0. 05). There were no statistical differences in Co,Cy,LB,B scores and total maturation scores between each gestational ages in severe brain injury group (all P>0. 05). Scores for Co, Cy,B and total maturation scores progressively increased with advancing gestational age in non-severe brain injury group( all P <0. 05),but there were no statistical differences between each gestational ages in LB scores(all P>0. 05). Follow-up results of 16 cases with severe brain injury:15 cases of DQ≤69,1 case of DQ 70－84,and no cases of DQ≥85; 130 cases of non-severe brain injury group:78 case of DQ≥85,42 cases of DQ 70－84,10 cases of DQ≤69. By chi-square analysis and Spearman rank correlation analysis,the results of aEEG total maturation scores were correlated with outcome of these preterm infants younger than 30 weeks of gestation ( r ＝0. 702,P <0. 05). Conclusion aEEG can provide important information of the status of cerebral function in preterm infants younger than 30 weeks of gestation and help to predict their outcome.

Analysis of the utilization of antibacterial drugs in 100 cases of old community-acquired pneumonia with chronic obstructive pulmonary disease / 中国基层医药

Objective@#To investigate the utilization of antibacterial drugs in the old community-acquired pneumonia (CAP) with chronic obstructive pulmonary disease(COPD) in our hospital.To analyze the rational application of antibacterial drugs, thus to provide a powerful reference for clinical diagnosis and treatment.@*Methods@#From June 2011 to June 2013, 100 patients with COPD and CAP were selected in Xiaolan People's Hospital.The average age was (76.95±6.57) years old, including 62 males and 38 females.The utilization of antibacterial drugs was investigated by retrospective study in the patients.@*Results@#In the course of treatment, the rate of using the antibacterial drugs in 100 patients was 100%, concerning 13 varieties of 5 major categories, including β-lactam (including β-lactam/β-lactamase inhibitors), quinolones, carbapenems, macrolides, aminoglycosides.The largest frequency was piperacillin/sulbactam, up to 92.Ceftezole, cefotian and azithromycin were less than 0.9 for DUI in DDDS ordering 10 drugs, it showed that the frequency was insufficient or the dosage was too small.For example, insufficient frequency of cephalosporin once a day and small dosage of azithromycin 0.25g once a day.Combination with two kinds of antimicrobial drugs was common, it was relatively rational between the combination of drugs, usually cephalosporins+ quinolones, β-lactam/β-lactamase inhibitors+ quinolones, β-lactam/β-lactamase inhibitors+ macrolides.@*Conclusion@#The etiology of 100 elderly patients with COPD and CAP in our hospital is mainly Gram-negative bacteria.The anti-infection treatment is mainly cefdiazine and piperacillin/sulbactam, and the combined drug was mainly quinolones.The drug regimen and treatment course are reasonable, there is a high prognosis in the patients.

Clinical research and drug review of epidermal growth factor receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer / 中华肿瘤杂志

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.

Clinical characteristics and antibiotic susceptibility features of different types of invasive infections caused by group B Streptococcus: a multicenter prospective study / 中华围产医学杂志

Objective To study the clinical manifestations and antibiotic sensitivity features of early-and late-onset invasive infections caused by group B Streptococcus (GBS). Methods A total of 96 infants with invasive GBS infections were enrolled prospectively from seven tertiary hospitals of GBS Infection Research Cooperative Group in southwest Fujian, such as Xiamen Maternal and Child Care Hospital, etc., from January 2016 to June 2018. According to the onset time of infection after birth, they were divided into early-onset GBS disease (GBS-EOD) group (<7 d, n=67) and the late-onset GBS disease (GBS-LOD) group (7-89 d, n=29). Clinical manifestations, disease spectrum, complications and outcomes of the two groups were compared. Drug sensitivity test was carried out using disk diffusion test. Chi-square or Fisher's exact test, two independent sample t-test or Mann-Whitney U tests were used for statistical analysis. Results (1) The average ages at onset in GBS-EOD and GBS-LOD groups were (15.8±6.7) h (0.5-142.0 h) and (25.0±8.1) d (9-89 d), respectively. The incidence of tachypnea, pallor, fever and convulsion were noted in 68.7% (46/67) vs 44.8% (13/29), 52.2% (35/67) vs 17.2% (5/29), 23.9% (16/67) vs 65.5% (19/29) and 7.5% (5/67) vs 48.3% (14/29) of GBS-EOD and GBS-LOD groups with χ2 values of 6.282, 10.199, 15.146 and 21.237 (all P<0.05). The main clinical manifestations of GBS-EOD were tachypnea and pallor, while most of the patients in the GBS-LOD group developed fever and convulsions. (2) The incidence of pneumonia, sepsis, meningitis, sepsis complicated by septic joints, pneumonia complicated by sepsis, sepsis complicated by meningitis and pneumonia complicated by sepsis and meningitis were noted in 43.3% (29/67) vs 20.7% (6/29), 9.0% (6/67) vs 17.2% (5/29), 0.0% (0/67) vs 3.4% (1/29), 0.0% (0/67) vs 6.9% (2/29), 31.3% (21/67) vs 13.8% (4/29), 6.0% (4/67) vs 31.0% (9/29) and 10.4% (7/67) vs 6.9% (2/29) of GBS-EOD and GBS-LOD groups. There was a statistically significant difference in the disease spectrum between the two groups (Fisher's exact test, all P<0.001). Compared with the GBS-LOD group, the GBS-EOD group had a higher incidence of pneumonia [85.1% (57/67) vs 41.4% (12/29), χ2=19.116, P<0.001] and a lower incidence of meningitis [16.4% (11/67) vs 41.4% (12/29), χ2=6.922, P=0.009]. Complications such as acute respiratory distress syndrome (ARDS), pulmonary hemorrhage, shock and persistent pulmonary hypertension of the newborn (PPHN) occurred much more in the GBS-EOD group than the GBS-LOD group [28.4% (19/67) vs 6.9% (2/29), 13.4% (9/67) vs 0.0% (0/29), 11.9% (8/67) vs 10.3% (3/29), 4.5% (3/67) vs 0.0% (0/29), χ2=13.683, P<0.001]. (3) Among the 96 patients, 23 (24.0%) had meningitis and 73 (76.0%) developed pneumonia and sepsis. Meningitis resulted in a higher fatality rate [17.4% (4/23) vs 4.1% (3/73), χ2=4.564, P=0.035] and longer average hospital stay [(37.2±12.6) vs (14.1±5.3) d, t=7.831, P<0.001] than pneumonia and sepsis. Seven out of the 19 meningitis survivors developed intracranial complications. (4) The overall fatality rate in this study was 7.3% (7/96) and no significant difference was found between GBS-EOD and GBS-LOD group [7.5% (5/67) vs 6.9% (2/29), χ2=0.010, P=0.982]. Among the 67 GBS-EOD infants, 58 (86.6%) occurred within 24 h and five of them died, but no death was reported in the other nine cases occurred after 24 h. (5) Totally 96 strains of GBS were isolated with 100% sensitivity to penicillin, ampicillin, cefazolin and meropenem, and 97% to vancomycin. Around 79.3%-91.0% of GBS isolates were resistant to clindamycin and erythromycin. Conclusions Clinial features vary greatly in GBS-LOD and GBS-EOD cases. Infants with meningitis have poor prognosis. The drug resistance rate of GBS to erythromycin and clindamycin are relatively high.

Relationship between intestinal fatty acid-binding protein expression and necrotizing enterocolitis in neonatal rat model / 中华围产医学杂志

Objective To analyze the role of intestinal fatty acid-binding protein (I-FABP) expression in a neonatal rat model of necrotizing enterocolitis (NEC).Methods A total of 24 newborn rats were randomly divided into two groups:control group (n=6) and NEC group (n=18).Rats in the NEC group were fed with formula and experienced hypoxia,reoxygenation,cold stress and sequentially Lipopolysaccharide (10 mg/kg) lavage for three consecutive days to establish NEC model,after which were respectively sacrificed on day 1,2 and 3 (six for each day).Those in the control group were all sacrificed on day 3.Ileocecal tissues were collected for morphological and histological analysis.I-FABP expression was detected using Western blot and immunohistochemistry (IHC).One-way analysis of variance,LSD-t test,Kruskal-Wallis H test,Mann-Whitney U test and Pearson's correlation analysis were used for statistical analysis.Results The NEC model (intestinal pathological score ≥ 2) was established successfully without causing death.Compared with the control group,the NEC group showed less body weight gain [M (P25-P75):1.00 (0.48-1.35) vs 1.74 (1.62-1.86),1.25 (0.75-1.40) vs 2.61 (2.53-2.99),1.35 (0.88-1.48) vs 3.60 (3.48-3.73);Z=-2.898,-2.903,-2.892;all P＜0.05] and higher intestinal pathological scores [(2 (2-3),3 (2-3),4 (3-4) vs 0 (0-1);all P＜0.05] on day 1,2 and 3.The intestinal pathological score on day 3 was significantly higher than that on day 2 and day 1 (both P＜0.05).Expression of I-FABP and the number of I-FABP positive enterocytes in the NEC model group were increased compared with those in the control group [Western blot:0.179 (0.179-0.186),0.231 (0.211-0.245),0.202 (0.192-0.225) vs 0.091 (0.086-0.093);IHC:59 (55-60),80 (83-86),80 (84-88) vs 44 (39-47);all P＜0.05].Moreover,the expression of I-FABP protein and the number of I-FABP positive enterocytes on day 2 and day 3 were significantly higher than those on day 1 (all P＜0.05).I-FABP expression was positively associated with intestinal pathological score (Western blot:r=0.932,95％CI:0.872-0.969;IHC:r=0.709,95％CI:0.484-0.872).Conclusions I-FABP is an efficient marker for NEC and correlates with the severity of intestinal injury.

Pharmacokinetics/Pharmacodynamics models of veterinary antimicrobial agents

Misuse and abuse of veterinary antimicrobial agents have led to an alarming increase in bacterial resistance, clinical treatment failure, and drug residues. To address these problems, consistent and appropriate dosage regimens for veterinary antimicrobial agents are needed. Pharmacokinetics/Pharmacodynamics (PK/PD) models have been widely used to establish rational dosage regimens for veterinary antimicrobial agents that can achieve effective prevention and treatment of bacterial diseases and avoid the development of bacterial resistance. This review introduces building methods for PK/PD models and describes current PK/PD research progress toward rational dosage regimens for veterinary antimicrobial agents. Finally, the challenges and prospects of PK/PD models in the design of dosage regimens for veterinary antimicrobial agents are reviewed. This review will help to increase awareness of PK/PD modeling among veterinarians and hopefully promote its development and future use.