The application of bladder stimulation technique in clean-catch urine collection of late newborns / 中国新生儿科杂志

Objective:To study the clinical value of bladder stimulation technique (BST) for clean-catch urine collection in late newborns.Methods:From November 2020 to March 2022, relatively stable late newborns hospitalized in the Department of Neonatology of our hospital were enrolled in the prospective randomized controlled trial. The newborns were assigned into BST group and control group. In BST group, urine was collected using BST (suprapubic tapping alternating with lumbosacral massage for 5 min) 20~30 min after feeding and specimen were collected using urine bag before and after BST. In the control group, urine was collected using urine bag method. The urine collection was considered successful if >1 ml of urine not contaminated by faeces were collected within 60 min. The t-test and χ 2 test were used for data analysis. Results:A total of 231 late newborns were included with 117 cases in BST group and 114 in control group. The rate of successful urine collection in BST group was higher than control group (65.8% vs. 39.4%).The time needed for successful urine collection [(30.2±8.5) min vs. (40.7±12.9) min], the incidences of faeces contamination (2.5% vs. 21.1%) and urine contamination (11.7% vs. 26.7%) in BST group were all significantly lower than control group(all P<0.05). Male and female newborns in BST group had similar success rates of urine collection (65.6% vs. 66.0%). Male newborns in BST group had similar urine contamination rate with control group (9.5% vs. 11.5%) and female newborns in BST group had significantly lower urine contamination rate than control group (14.3% vs. 47.4%, P<0.05). Urine was successfully collected in 71 newborns in BST group with median duration of BST for 81 (61,132) s. No adverse effects were observed except for transient consolable crying. Conclusions:Compared with urine bag collection method, BST improves successful urine collection rates and reduces the time needed for urine collection and urine contamination rates (especially for females).

Risk factors, diagnosis and treatment of transient hyperinsulinemic hypoglycemia in newborns / 中国新生儿科杂志

Objective:To study the risk factors, diagnosis and treatment of transient hyperinsulinemic hypoglycemia (HH) in newborns.Methods:From January 2016 to December 2020, newborns with transient HH (HH group) admitted to our hospital were enrolled in this retrospective nested case-control study. Newborns with similar gestational age (GA) (differences of GA<2 w) without HH were matched with 1∶2 ratio as the non-HH group. Clinical characteristics of the two groups were compared and the risk factors and therapeutic results of HH in newborns were analyzed using SPSS 20.0 statistical software.Results:A total of 39 cases were included in the HH group and 75 cases were matched in the non-HH group. The proportion of small for gestational age (SGA) [51.3%(20/39) vs. 32.0%(24/75)], the amount of amino acids (AA) in intravenous infusion[1.0(0.0,1.0) g/(kg·d) vs. 0.0(0.0,1.0) g/(kg·d)], the incidence of hypoglycemia [(4.3±1.9) times vs. (3.6±1.3) times] and the maximum glucose infusion rate (GIR)[(8.3±2.5) mg/(kg·min) vs. (7.4±1.1) mg/(kg·min)] in the HH group were higher than the non-HH group (all P<0.05). The platelet count in the HH group were lower than the non-HH group [(186.9±60.9)×10 9/L vs. (215.3±61.7)×10 9/L, P<0.05]. SGA ( OR=2.535, 95% CI 1.077~5.971), the amount of intravenous AA ( OR=2.180, 95% CI 1.029~4.619) and the maximum GIR ( OR=1.405, 95% CI 1.088~1.815) were independent risk factors for transient HH. In the HH group, 28/39 cases were treated with Diazoxide or Octreotide and the therapeutic effects were good with few adverse drug reactions (ADR). 37/39 cases were recovered within 28 d of birth and the other 2 cases were recovered at 2.5 m and 3.5 m, respectively. Conclusions:SGA, the amount of intravenous AA and higher GIR are risk factors for transient HH in newborns. Diazoxide or Octreotide are effective with few ADR in the treatment of transient HH. Most patients will recover from transient HH in 2 w to 3 m.

Synergistic effect of Hsp90 inhibitor ginkgolic acids C15 ꞉1 combined with paclitaxel on nasopharyngeal carcinoma / 中南大学学报(医学版)

OBJECTIVES@#Nasopharyngeal cracinoma is a kind of head and neck malignant tumor with high incidence and high mortality. Due to the characteristics of local recurrence, distant metastasis, and drug resistance, the survival rate of patients after treatment is not high. Paclitaxel (PTX) is used as a chemotherapy drug in treating nasopharyngeal carcinoma, but nasopharyngeal carcinoma cells are easy to develop resistance to PTX. Inhibition of heat shock protein 90 (Hsp90) can overcome common signal redundancy and resistance in many cancers. This study aims to investigate the anti-tumor effect of ginkgolic acids C15꞉1 (C15:1) combined with PTX on nasopharyngeal carcinoma CNE-2Z cells and the mechanisms.@*METHODS@#This experiment was divided into a control group (without drug), a C15:1 group (10, 30, 50, 70 μmol/L), a PTX group (5, 10, 20, 40 nmol/L), and a combination group. CNE-2Z cells were treated with the corresponding drugs in each group. The proliferation of CNE-2Z cells was evaluated by methyl thiazolyl tetrazolium (MTT). Wound-healing assay and transwell chamber assay were used to determine the migration of CNE-2Z cells. Transwell chamber was applied to the impact of CNE-2Z cell invasion. Annexin V-FITC/PI staining was used to observe the effect on apoptosis of CNE-2Z cells. The changes of proteins involved in cell invasion, migration, and apoptosis after the combination of C15꞉1 and PTX treatment were analyzed by Western blotting.@*RESULTS@#Compared with the control group, the C15꞉1 group and the PTX group could inhibit the proliferation of CNE-2Z cells (all P<0.05). The cell survival rates of the C15꞉1 50 μmol/L combined with 5, 10, 20, or 40 nmol/L PTX group were lower than those of the single PTX group (all P<0.05), the combination index (CI) value was less than 1, suggesting that the combined treatment group had a synergistic effect. Compared with the 50 μmol/L C15꞉1 group and the 10 nmol/L PTX group, the combination group significantly inhibited the invasion and migration of CNE-2Z cells (all P<0.05). The results of Western blotting demonstrated that the combination group could significantly down-regulate Hsp90 client protein matrix metalloproteinase (MMP)-2 and MMP-9. The results of double staining showed that compared with the 50 μmol/L C15꞉1 group and the 10 nmol/L PTX group, the apoptosis ratio of CNE-2Z cells in the combination group was higher (both P<0.05). The results of Western blotting suggested that the combination group could decrease the Hsp90 client proteins [Akt and B-cell lymphoma-2 (Bcl-2)] and increase the Bcl-2-associated X protein (Bax).@*CONCLUSIONS@#The combination of C15꞉1 and PTX has a synergistic effect which can inhibit cell proliferation, invasion, and migration, and induce cell apoptosis. This effect may be related to the inhibition of Hsp90 activity by C15꞉1.

Correlation between dyslipidemia and rheumatoid arthritis associated interstitial lung disease / 北京大学学报(医学版)

OBJECTIVE@#To study the correlation between dyslipidemia and rheumatoid arthritis associa-ted interstitial lung disease (RA-ILD) by retrospective analysis of the clinical data.@*METHODS@#The clinical data of patients with rheumatoid arthritis (RA), who were hospitalized in the Department of Rheumatism and Immunology of Peking University Shenzhen Hospital from January 2015 to July 2020 and fulfilled the criteria of the 2010 Rheumatoid Arthritis Classification Criteria established by American College of Rheumatology/European League Against Rheumatism collaborative initiative, were collected and analyzed.@*RESULTS@#There were 737 RA patients included, of whom 282(38.26%)were with interstitial lung disease (ILD). The median time from the onset of the first RA-related clinical symptoms to the onset of ILD was 13 years (95%CI 11.33-14.67). By multivariate Logistic regression analysis, we found that low-density lipoprotein cholesterol (LDL-C) was an independent risk factor for RA-ILD (OR 1.452, 95%CI 1.099-1.918, P=0.009), whereas high-density lipoprotein cholesterol (HDL-C) was a protective factor for RA-ILD (OR 0.056, 95%CI 0.025-0.125, P < 0.001). The RA patients with high LDL-C or low HDL-C had higher incidence of ILD than that of the RA patients with normal LDL-C or HDL-C(57.45% vs. 36.96%, P < 0.001; 47.33% vs. 33.81%, P < 0.001, respectively). The median time of ILD onset in the RA patients with low HDL-C was shorter than that of the RA patients with normal HDL-C [10.0(95%CI 9.33-10.67)years vs.17.0 (95%CI 14.58-19.42) years, P < 0.001]. HDL-C level was negatively correlated with disease activity. Among the RA-ILD patients, the patients with low HDL-C had higher percentage of usual interstitial pneumonia (UIP) then that of the patients with normal HDL-C (60.00% vs. 53.29%, P=0.002). The RA-ILD patients with high LDL-C had higher incidence rate of decrease in forced vital capacity (FVC) than that of the RA-ILD patients with normal LDL-C (50.00% vs. 21.52%, P=0.015). The RA-ILD patients with low HDL-C had higher incidence rate of decrease in FVC (26.92% vs. 16.18%, P=0.003) and carbon monoxide diffusion (80.76% vs. 50.00%, P=0.010) than that of RA-ILD patients with normal HDL-C.@*CONCLUSION@#LDL-C was possibly a potential independent risk factor for RA-ILD. HDL-C was possibly a potential protective factor for RA-ILD. HDL-C level was negatively correlated with disease activity of RA. The median time of ILD onset in the RA patients with low HDL-C was significantly shorter than that of the RA patients with normal HDL-C.

Poly-G for tumor matched samples chronicles the evolution of human colorectal cancer / 中华肿瘤杂志

Objective: To analyze poly-guanine (poly-G) genotypes and construct the phylogenetic tree of colorectal cancer (CRC) and provide an efficient and convenient method for the study of intra-tumor heterogeneity and tumor metastasis pathway. Methods: The clinicopathological information of patients with primary colorectal cancer resection with regional lymph node metastases were retrospectively collected in the Department of General Surgery, General Hospital of Tianjin Medical University from January 2017 to December 2017. The paraffin sections of the paired tumor samples were performed consecutively, and multi-region microdissection was performed after histogene staining. The phenol-chloroform extraction and ethanol precipitation scheme was used to obtain DNA, and Poly-G multiplex PCR amplification and capillary electrophoresis detection were performed. The correlation between Poly-G mutation frequency and clinicopathological parameters was analyzed. Based on the difference of Poly-G genotypes between paired samples, the distance matrix was calculated, and the phylogenetic tree was constructed to clarify the tumor metastasis pathway. Results: A total of 237 paired samples were collected from 20 patients including 134 primary lesions, 66 lymph node metastases, 37 normal tissues, and Poly-G mutation was detected in 20 patients (100%). The mutation frequency of Poly-G in low and undifferentiated patients was (74.10±23.11)%, higher than that in high and medium differentiated patients [(31.36±12.04)%, P<0.001]. In microsatellite instability patients, the mutation frequency of Poly-G was (68.19±24.80)%, which was higher than that in microsatellite stable patients [(32.40±14.90)%, P=0.003]. The Poly-G mutation frequency was not correlated with age, gender, and pathological staging (all P>0.05). Based on Poly-G genotype difference of the paired samples, the phylogenetic trees of 20 patients were constructed, showing the evolution process of the tumor, especially the subclonal origins of lymph node metastasis. Conclusion: Poly-G mutations accumulate in the occurrence and development of CRC, and can be used as genetic markers to generate reliable maps of intratumor heterogeneity in large numbers of patients with minimal time and cost expenditure.

Progress in preparation and application of sodium alginate microspheres / 生物医学工程学杂志

Sodium alginate (SA) is a kind of natural polymer material extracted from kelp, which has excellent biocompatibility, non-toxicity, biodegradability and abundant storage capacity. The formation condition of sodium alginate gel is mild, effectively avoiding the inactivation of active substances. After a variety of preparation methods, sodium alginate microspheres are widely used in the fields of biomaterials and tissue engineering. This paper reviewed the common methods of preparing alginate microspheres, including extrusion, emulsification, electrostatic spraying, spray drying and coaxial airflow, and discussed their applications in biomedical fields such as bone repair, hemostasis and drug delivery.

Role of platelets aggregation in the process of ductus arteriosus closure of newborn pups / 中华危重病急救医学

Objective:To investigate the role of platelets aggregation in the developing process of ductus arteriosus closure of newborn pups, and the effect of platelet membrane glycoprotein Ⅱb-Ⅲa (GPⅡb-Ⅲa) receptor antagonist (tirofiban).Methods:Four 24-month-old Beagle bitches were selected and numbered 1, 2, 3, and 4 respectively, and their pups were removed by cesarean section in two batches 1-2 days before the expected date of delivery. Bitches 1 and 2 were the first batch. Eighteen newborn pups were removed after cesarean section as the control group. They were divided into three subgroups: 1-hour subgroup, 4-hour subgroup, and 12-hour subgroup according to postnatal time point, with 6 pups in each subgroup. The newborn pups were injected with normal saline 10 mL/kg via jugular vein immediately after birth. Bitches 3 and 4 were the second batch. Nineteen newborn pups were removed by cesarean section as tirofiban group. They were also divided into three subgroups: 1-hour subgroup ( n = 6), 4-hour subgroup ( n = 6), and 12-hour subgroup ( n = 7) according to the postnatal time point. The newborn pups were injected with tirofiban hydrochloride injection 10 mL/kg (10 mL injection including 2.5 mg of tirofiban) via jugular vein immediately after birth. The diameter of ductus arteriosus was measured by echocardiography. Ductus arteriosus was removed by surgical dissection and divided into two parts. Western blotting and immunohistochemistry were used to detect the expression of platelet membrane GPⅡb-Ⅲa, respectively. Results:In the control group, 1 newborn pup died at 0.5 hour after birth in the 1-hour subgroup. The experiment was completed by 19 in the tirofiban group. Ductus arteriosus of all pups were not closed in 1-hour subgroups of the two groups, and there was no significant difference in the diameter of ductus arteriosus between the control group and the tirofiban group (mm: 1.72±0.08 vs. 1.70±0.11, P > 0.05). Ductus arteriosus of 1 newborn pup in 4-hour subgroup of the control group was closed, but the ductus arteriosus of all the newborn pups in 4-hour subgroup of the tirofiban group were not closed. The diameter of ductus arteriosus of the tirofiban group was significantly larger than that of the control group (mm: 1.52±0.15 vs. 0.95±0.48, P < 0.05). Ductus arteriosus of all pups were closed in 12-hour subgroup of the control group, but the ductus arteriosus of 2 pups of the tirofiban group were still not closed, with the diameter of ductus arteriosus of 1.0 mm and 1.1 mm, respectively. Western blotting showed that at 1-hour, 4-hour and 12-hour after birth, the expression of platelet membrane GPⅡb-Ⅲa was gradually increased in ductus arteriosus of newborn pups of the two groups. The expression of GPⅡb-Ⅲa in 1-hour subgroup of the tirofiban group was significantly lower than that in the control group (GPⅡb-Ⅲa/β-actin: 0.67±0.07 vs. 0.84±0.16, P < 0.05). The expression of GPⅡb-Ⅲa in 4-hour and 12-hour subgroups of the tirofiban group were slightly lower than those in the control group (GPⅡb-Ⅲa/β-action: 0.85±0.12 vs. 0.95±0.11 in 4-hour subgroup, 1.04±0.16 vs. 1.09±0.17 in 12-hour subgroup, both P > 0.05). Immunohistochemistry showed that the change trend of platelet membrane GPⅡb-Ⅲa in ductus arteriosus of newborn pups in both groups was similar to the results of Western blotting. Conclusions:The ductus arteriosus of newborn pups begin to close 1-4 hours after birth, and all closed at 12 hours after birth. The expression of platelet membrane GPⅡb-Ⅲa in ductus arteriosus increase gradually after birth, and the platelet aggregation may participate in and promote ductus arteriosus closure to some extent. Tirofiban, a platelet membrane GPⅡb-Ⅲa receptor antagonist, may delay ductus arteriosus closure of newborn pups to some extent by inhibiting platelet aggregation.

Effects of non-invasive positive pressure ventilation on plasma B-type natriuretic peptide level and Tei index of right ventricle in preterm infants / 中华全科医师杂志

Objective:To investigate the effects of non-invasive positive pressure ventilation (NPPV) on plasma B-type natriuretic peptide (BNP) level and Tei index of right ventricle in preterm infants.Methods:Premature infants of gestational age<34 weeks with respiratory distress syndrome who were admitted in Neonatal Intensive Care Unit of Xuzhou Central Hospital and requiring for NPPV from December 2018 to October 2020, were enrolled in the study. Patients were randomly divided into two groups 46 patients received nasal continuous positive airway pressure ventilation (NCPAP group) and 49 patients received bi-level positive airway pressure ventilation (BiPAP group); 42 preterm infants of gestational age<34 weeks and without NPPV were selected as the control group. The plasma BNP, Tei index of right ventricle, mean airway pressure and oxygen index at 0-12 h and 48-60 h after NPPV were monitored in NCPAP group and BiPAP group. The plasma BNP and Tei index of right ventricle at 0-12 h and 48-60 h after admission were monitored in the control group. SPSS 20.0 statistical software was used for data analysis.Results:(1)The plasma BNP and Tei index of right ventricle at 48-60 h after NPPV were significantly higher than those at 0-12 h after NPPV in NCPAP group and BiPAP group [NCPAP group: (287.5±155.5) vs. (179.9±102.3) ng/L, (0.43±0.08) vs. (0.38±0.06); BiPAP group: (303.1±135.4) vs. (186.5±95.6) ng/L, (0.45±0.08) vs. (0.39±0.06); t=6.00, 3.34, 7.47, 4.48; all P<0.05]. There were no significant differences in the plasma BNP and Tei index of right ventricle at 48-60 h and 0-12 h after admission in the control group [(181.9±86.8) vs. (169.5±78.9) ng/L, (0.34±0.05) vs. (0.36±0.05); t=0.83, -1.59; all P>0.05].(2) There were no significant differences in the plasma BNP and Tei index of right ventricle at 48-60 h after NPPV between NCPAP group-and BiPAP group (all P>0.05), but they were significantly higher than those in control group at 48-60 h after admission(all P<0.05). (3)The mean airway pressure and oxygen index at 48-60 h after NPPV in NCPAP group and BiPAP group showed a decrease trend compared to those at 0-12 h after NPPV, but the differences were not significant [NCPAP group: (6.8±1.2) vs. (7.0±1.3) cmH 2O(1 cmH 2O=0.098 kPa), (5.7±2.1) vs. (6.1±2.3); BiPAP group: (7.0±1.3) vs. (7.2±1.2) cmH 2O, (5.5±2.0) vs. (5.8±2.1); t=-1.05, -0.80, -1.88, -0.67; all P>0.05]; while there were no significant differences between the two groups (all P>0.05). (4)There was a positive correlation between the plasma BNP and mean airway pressure ( r=0.48, P<0.001), but no correlation between Tei index of right ventricle and mean airway pressure ( r=0.17, P=0.119) at 48-60 h after NPPV. Conclusion:The cardiac function indexes such as plasma BNP and Tei index of right ventricle in preterm infants are increased at 48-60 h after NPPV. When mean airway pressure is the same, the effects of NCPAP and BiPAP on plasma BNP and Tei index of right ventricle in preterm infants are similar.

Clinical research of the LISA technique combined with caffeine in the treatment of respiratory distress syndrome in preterm infants / 中华急诊医学杂志

Objective:To evaluate the efficacy and safety of less invasive surfactant administration (LISA) combined with caffeine citrate in the treatment of respiratory distress syndrome (RDS) in preterm infants receiving continuous positive airway pressure (NCPAP) ventilation.Methods:From August 2019 to April 2021, a total of 112 preterm infants with RDS (26 weeks≤gestational age ≤32 weeks) who were hospitalized in the Neonatal Intensive Care Unit of Xuzhou Central Hospital, were chosen as research subjects. The patients were randomly divided into the LISA combined treatment group ( n=58) and the INSURE group ( n=54). In the LISA combined treatment group, a LISA tube was inserted through the vocal cords under direct vision with a direct laryngoscope and then infused with pulmonary surfactant (PS) into the lung when NCPAP ventilation was applied, and caffeine citrate was given intravenously. In the INSURE group, the patients were endotracheally intubated and infused with PS into the lung through an endotracheal tube, and then extubated and put on NCPAP again. The following indicators were examined: the general clinical data, results of blood gas analysis at 1 h and 6 h after infusion of PS into the lung, clinical efficacy and related complications. Results:①No significant differences were found between the two groups in the general clinical data (all P>0.05).Intra-group comparison within LISA combined treatment group or INSURE group showed that partial pressure of arterial carbon dioxide (PaCO 2), partial pressure of arterial oxygen (PaO 2) of blood gas analysis and PaO 2/fraction of inspired oxygen (P/F) at 1 h and 6 h after infused PS into the lung were all improved compared to those of before treatment, and the differences were statistically significant (all P<0.05). The PaO 2 and P/F in the LISA combined treatment group at 1 h and 6 h after breath support therapy were higher than those in the INSURE group, while PaCO 2 was lower than that in the INSURE group, and the differences were statistically significant (all P<0.05). The duration of noninvasive ventilation, total oxygen inhalation, re-administration of PS, failure rate of machine withdrawal, the rate of tracheal intubation within 72 h and the times of apnea in the LISA combined treatment group were significantly shorter, or lower, or less than those in the INSURE group [3.0 (1.0, 18.0) d vs. 7.5 (2.0, 22.0) d, 5.5 (3.0, 21.0) d vs. 10.5 (4.0, 28.0) d, 9 (15.5%) vs. 17 (31.5%), 6 (10.3%) vs. 14 (25.9%), 5 (8.6%) vs. 12 (22.2%), 5.0 (3.0, 21.0) times vs. 15.0 (4.0, 28.0) times], and the differences were all statistically significant (all P<0.05). The incidence of bronchopulmonary dysplasia in the LISA combined treatment group was less than that in the INSURE group [(5 (8.6%) vs. 13 (24.1%)], and the difference was statistically significant ( P<0.05). There was no significant difference between the two groups in other complications( P>0.05). Conclusions:Compared with INSURE, the LISA technique combined with caffeine citrate can effectively improve oxygenation, reduce the mechanical ventilation rate, shorten the duration of noninvasive mechanical ventilation, and reduce the incidence of BPD in the treatment of premature infants with RDS at the gestational age of 26-32 weeks.

Efficacy and safety of initial treatment with ibuprofen or paracetamol and rescue treatment with high-dose ibuprofen in preterm infants with patent ductus arteriosus / 中华全科医师杂志

Objective:To investigate the efficacy and safety of initial treatment with ibuprofen or paracetamol and rescue treatment with high-dose ibuprofen in preterm infants with haemodynamically significant patent ductus arteriosus (hsPDA).Methods:The preterm infants (gestational age ≤ 32 weeks) with hsPDA who were admitted to neonatal intensive care unit (NICU) of Xuzhou Central Hospital from October 2016 to November 2019 were enrolled in the study. A total of 110 eligible cases were included and randomly divided into three groups for initial treatment: 38 cases received oral ibuprofen 10 mg/kg, and 5 mg/kg after 24 h and 48 h (ibuprofen group), 37 cases received oral paracetamol 15 mg/kg, q.8.h for 3 d (paracetamol group) and 35 cases received oral injection water 1 ml/kg, and 0.5 ml/kg after 24 h and 48 h (conservative management group). The preterm infants who failed in the initial treatment were given high-dose ibuprofen for rescue treatment (oral ibuprofen 20mg/kg, and 10 mg/kg after 24 h and 48 h). Serum creatinine, cystatin C, glutamic-pyruvic transaminase (GPT), total bilirubin, fecal occult blood and urinary prostaglandin E 2 were measured; echocardiography and brain color Doppler ultrasonography examinations were performed before and after treatment. Urine output and complications were recorded. The data were analyzed by ANOVA, t-test, non-parametric test, chi-square test and Pearson correlation coefficient with SPSS 20.0 statistical software. Results:During initial treatment, the success rates of ibuprofen group and paracetamol group were higher than that of conservative management group [71.1% (27/38) and 70.3%(26/37) vs. 40.0% (14/35), P=0.008 and 0.010]. Thirty one patients, who failed in initial treatment, received rescue treatment (8, 7, 16 cases from ibuprofen, paracetamol and conservative groups, respectively). The success rate of rescue treatment with high-dose ibuprofen was 58.1% (18/31). During initial treatment, there were no significant differences in the incidence of oliguria, upper gastrointestinal bleeding, positive fecal occult blood tests, Ⅲ-Ⅳ grade intraventricular hemorrhage, and ≥Ⅱ stage necrotizing enterocolitis among the three groups (all P>0.05). There were no significant differences in the incidence of above complications between rescue treatment and initial treatment [6.5% (2/31) vs. 6.4%(7/110), 3.2%(1/31) vs. 4.5%(5/110), 12.9%(4/31) vs. 6.4%(7/110), 0 vs. 4.5%(5/110), 3.2%(1/31) vs. 1.8%(2/110), all P>0.05]. The changes of serum creatinine and GPT before and after treatment were not significant in all groups ( P>0.05). Serum cystatin C were increased in both ibuprofen group[(0.44±0.17)μmol/L] and paracetamol group [(0.18±0.09)μmol/L] after treatment ( t=-15.70, -14.64; P<0.001), and the increase in ibuprofen group was greater than that in paracetamol group ( P<0.001). Urinary prostaglandin E 2 were decreased in both ibuprofen group [(-11.63±3.70)ng/L] and paracetamol group[(-4.89±1.91)ng/L] after treatment ( t=15.57, 7.03; P<0.001), and the decrease in ibuprofen group was greater than that in paracetamol group ( P<0.001). Serum cystatin C was not significantly increased after high dose ibuprofen rescue treatment [(1.67±0.17)mg/L vs.(1.71±0.21)mg/L; t=-1.12, P=0.273]. Conclusion:Both initial treatment with ibuprofen or paracetamol and rescue treatment with high-dose ibuprofen can effectively promote hsPDA closure in preterm infants without increase of complications. However, renal function indexes such as urine output and serum cystatin C should be monitored. The high-dose ibuprofen is relatively safe, and can be used as one of rescue treatment.

Application and experience of laparoscopy for gastric cancer after transformation therapy (report of 7 cases) / 中国医师杂志

Objective:To investigate the application value of laparoscopy for stage Ⅳ gastric cancer after transformation therapy.Methods:The clinical data of 7 patients with advanced gastric cancer who underwent laparoscopic surgery after transformation therapy in the First Affiliated Hospital of Hebei North University from January 2016 to December 2020 were retrospectively analyzed. Seven patients were diagnosed as stage Ⅳ gastric cancer by computed tomography (CT), positron emission tomography (PET-CT) and laparoscopy, and underwent paclitaxel based conversion therapy. After evaluating the curative effect, they underwent surgical resection. The intraoperative and postoperative conditions and survival rate of the patients were analyzed.Results:After transformation therapy, 6 patients (85.7%) had partial remission, 1 patient (14.3%) had stable disease, and the overall effective rate was 6/7. Laparoscopic-assisted surgery was performed in 3 patients, and 4 patients were converted to laparotomy. The operation time was (297.9±35.6)min, the intraoperative blood loss was (257.0±106.0)ml, the number of dissected lymph nodes was (38.4±9.1), the gastric tube indwelling time was (72.4±9.6)h, the jejunal feeding tube indwelling time was (15.4±5.6)d, and the liquid diet time was (8.6±3.4)d, the length of hospital stay was (17.1±5.5)d. The postoperative complication rate was 3/7, and there were no unplanned secondary operations and deaths. R0 resection was performed in 6 cases, and R1 resection in 1 case. Tumor regression grade (TRG) classification: 5 cases were grade 2 and 2 cases were grade 3. The median progression free survival of the 7 patients was 15.3 months, the median overall survival was 21.6 months, and the 1-year survival rate was 6/7.Conclusions:Laparoscopy has irreplaceable value in the staging and efficacy judgment of transformation therapy for gastric cancer. However, after transformation therapy, the tissue edema increases, the tumor boundary becomes more unclear, and the surgical operation becomes more difficult. Therefore, it is not necessary to force the laparoscopic operation, and switch to laparotomy according to the situation.

The effects of hyperbilirubinemia on the myocardium of newborn rats / 中国新生儿科杂志

Objective:To study the influences of different levels of hyperbilirubinemia on the myocardium of newborn rats.Methods:Ninety-six 7-day-old newborn SD rats were selected and randomly assigned into control group (n=32, intraperitoneal injection of normal saline 0.5 ml), test group 1 (n=32, intraperitoneal injection of bilirubin solution 100 mg/kg) and test group 2 (n=32, intraperitoneal injection of bilirubin solution 200 mg/kg). Four time points were set at 0 h, 8 h, 24 h and 48 h. The general conditions of 8 rats from every group at each time point were recorded. The total serum bilirubin (TSB), cardiac troponin I (cTnI),heart fatty acid-binding protein (H-FABP) and B-type natriuretic peptide (BNP) were examined. The heart was removed and the pathological changes of the myocardium were observed under microscope. The caspase-3, B-cell lymphoma-2 protein (bcl-2) and bcl-2-associated X protein (bax) were tested. Using SPSS 20.0 statistical software, two-way ANOVA analysis of variance was conducted.Results:The TSB in test group 1 and 2 at 8~48 h were 2.5~4.4 times and 3.5~7.4 times higher than at 0 h [(20.8±3.0~36.5±10.4) μmol/L and (31.9±12.3~67.4±19.0) μmol/L vs. (8.4±2.1) μmol/L and (9.1±2.9) μmol/L]. No significant changes existed in cardiac histopathology at each time point among the three groups. At 48 h, as TSB level increased, the expression of apoptosis-related proteins caspase-3 and bax increased and the expression of bcl-2 decreased. Significant differences existed in the protein levels between any two groups (all P<0.05), except that bcl-2 in test group 1 was similar to control group ( P=0.255). With the prolonged duration of hyperbilirubinemia in test group 2, the expression of caspase-3 and bax increased, while the expression of bcl-2 decreased. Statistically significant differences existed in the protein levels between any two time points (all P<0.05), except that bax in 8 h subgroup was similar to 12 h subgroup ( P=0.820), and bcl-2 in 8 h subgroup was similar to 0 h subgroup ( P=0.064). The cTnI at 8 h, 24 h and 48 h in test group 1 and 2 were all significantly higher than the control group (all P<0.05),however, no significant differences existed between test group 1 and 2 (all P>0.05). H-FABP and BNP showed no significant differences among the three groups at any time point (all P>0.05). Conclusions:Hyperbilirubinemia can induce apoptosis of myocardial cells in newborn rats in a concentration- and time-dependent manner. Hyperbilirubinemia shows no significant effects on cardiac tissue pathology. Hyperbilirubinemia may cause mild injury to myocardium of newborn rats. The injury shows no correlation with TSB level and BNP level was not influenced.

Single Cell Traction Force Measured by Foldable Microplates / 医用生物力学

Objective To fabricate a foldable microplate for single cell culture and establish finite element model of the folding microplate, so as to calculate traction force of single cells during contraction in three-dimensional (3D) state.Methods The folding angle of the microplate casued by cell traction force was calculated. Then the relation between bending moment and folding angle as well as the relation between traction force and bending moment were derived by using finite element simulation, so as to realize the characterization of traction force for singel cell in 3D state.Results The folding angles of the microplate with HSF and MC3T3-E1 cells in 3D state were 73°-173° and 49°-138°, respectively. The single cell traction forces of HSF and MC3T3-E1 cells were 55-210 nN and 52-161 nN, respectively.Conclusions The proposed method for measuring traction force of single cells in 3D state by fabricating the foldable microplate for single cell culture will provide some references for further development of calculating traction forces in 3D cell adhesion, spreading and migration.

PFKL, a novel regulatory node for NOX2-dependent oxidative burst and NETosis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Neutrophils are predominant leukocytes in the circulation, which are essential for killing invading pathogens via the activation of effector responses and the production of reactive oxygen species (ROS), also named as "oxidative burst." When infected, activated neutrophils fight bacteria, fungi, and viruses through oxidative burst, phagocytosis, degranulation, and the production of neutrophil extracellular traps (NETs) in a neutrophil death process named as "NETosis" (Mutua and Gershwin, 2021). NETs, consisting of DNA fibers decorated with modified histones and numerous antimicrobial proteins from cytoplasmic granules and the nucleus, can either be beneficial or detrimental (Mutua and Gershwin, 2021). Several pathways can lead to this death process. In response to various stimuli, NETosis traps and clears pathogens, facilitating phagocytosis by other neutrophils and phagocytes. However, excessive NETosis often results in disease due to increasing the pro-inflammatory response and perpetuating the inflammatory condition (Hellebrekers et al., 2018; Hidalgo et al., 2019; Klopf et al., 2021). Accordingly, inhibiting aberrant NETosis may alleviate the severity of various autoimmune and inflammatory diseases.

The role of polyomavirus enhancer activator 3 in hyperoxic-induced alveolar epithelial cells type Ⅱ injury / 中华实用儿科临床杂志

Objective:To investigate the role of polyomavirus enhancer activator 3 (PEA3) in hyperoxia-induced injury of type Ⅱ alveolar epithelial cells (AEC Ⅱ) and the underlying mechanism.Methods:AEC Ⅱ cells were cultured in vitro and divided into hyperoxia group and normoxia group.After 24 h, 48 h and 72 h of hyperoxia or air treatment, cells were collected and the best treatment time was selected at 48 h. AEC Ⅱ cells were divided into 3 groups: control group, negative control group (transfected with negative control) and PEA3 over expression group (transfected with PEA3 overexpression plasmid). Each group was further divided into hyperoxia subgroup and normoxia subgroup.Cells were harvested at 48 h after hyperoxia or normoxia treatment.Reactive oxygen species (ROS), Nod-like receptor domain 3 (NLRP3), monocyte chemoattractant protein-1 (MCP-1), interleukin(IL)-1β, IL-6, IL-8, IL-18, surfactant protein C (SP-C), aquaporins 5 (AQP5), PEA3 and manganese superoxide dismutase (MnSOD) levels were detected.Differences were compared by the t-test and repeated measures analysis of variance using SPSS 20.0 statistical software. Results:The interaction of grouping and treatment duration had significant effects on ROS, IL-1β, IL-6, IL-8, IL-18, SP-C and AQP5 levels in AEC Ⅱ cells ( F=19.857, 20.132, 23.133, 18.673, 28.341, 27.333 and 34.217, respectively, all P<0.05). At 24 h, 48 h and 72 h, ROS level in hyperoxia group was 1.78, 1.94 and 2.26 times higher than that in normoxia group ( t=18.649, 17.486 and 19.385, respectively all P<0.05). NLRP3 and MCP-1 levels were significantly upregulated in hyperoxia group.IL-1β level was 1.33, 1.69, and 1.65 times higher in hypoxia group at 24 h, 48 h and 72 h than that of normoxia group; IL-6 level was 1.26, 1.56 and 2.12 timers higher; IL-8 level was 1.13, 1.47 and 2.34 times higher; and IL-18 level was 1.46, 1.72 and 1.95 times higher, respectively (all P<0.05). The protein expression of SP-C was downregulated, while that of AQP5 was significantly upregulated in hypoxia group.The RNA expression of SP-C was 22%, 63% and 72% lower in hypoxia group than that in normoxia group at 24 h, 48 h and 72 h ( t=3.982, 16.328 and 20.259, P<0.05, respectively), and that of AQP5 was 1.92, 5.23 and 7.36 times higher ( t=14.631, 18.945 and 19.521, respectively, all P<0.05). There were significant differences in ROS, IL-1β, IL-6, IL-8, IL-18, SP-C and AQP5 levels at 24 h, 48 h and 72 h in hyperoxia group ( F=22.343, 20.566, 23.701, 19.222, 32.146, 40.278 and 37.107, respectively, all P<0.05). After 48 h of PEA3 overexpression, compared with the hyperoxic negative control group, ROS level in hyperoxic AEC Ⅱ cells overexpressing PEA3 decreased by 34% ( t=14.635, P<0.05). NLRP3 and MCP-1 were downregulated in hyperoxic AEC Ⅱ cells after overexpression of PEA3.IL-1β, IL-6, IL-8 and IL-18 levels decreased by 29%, 22%, 27% and 18%, respectively ( t=15.895, 17.872, 18.749 and 15.274, all P=0.000). SP-C was upre-gulated and AQP5 was downregulated by overexpression of PEA3 in hyperoxic AEC Ⅱ cells.In addition, PEA3 and MnSOD levels were significantly enhanced. Conclusions:Overexpression of PEA3 can alleviate the increase of ROS level in AEC Ⅱ cells, block the activation of various inflammatory pathways and reduce the transformation from AEC Ⅱ to AEC Ⅰ cells via enhancing MnSOD level.

Analysis of clinical cross-control trial results of an smartphone application in screening neonatal jaundice / 中华实用儿科临床杂志

Objective:To evaluate the correlation, consistency and safety of an smartphone application (APP) in screening neonatal jaundice using the smartphone based on the image-based bilirubin (IBB) and transcutaneous bilirubin (TcB).Methods:From July to October 2018, neonates with the age ≤28 d and gestational age ≥35 weeks who were admitted to Department of Neonatal and Obstetrics, Xuzhou Central Hospital without blue light phototherapy were recruited.They were randomly divided into two groups to measure the jaundice value of skin in front of sternum by a cross-control analysis.Jaundice level in group Ⅰ was first measured using the Nezhabaobei? APP in iPhone 6, and then measured using the JM-103 transcutaneous jaundice instrument as the control device.In group Ⅱ, jaundice level was sequencially measured by the control device and the Nezhabaobei? APP.Sex, age, gestational age, birth weight and the mean value of three consecutive tests were recorded.The Pearson′s correlation analysis, Bland-Altman plots consistency analysis, t test and receiver operating characteristic (ROC) curve were used for statistical analysis. Results:A total of 185 eligible neonates were enrolled, including 99 males and 86 females, with the median age of 5 d (3-8 d), gestational age of (37.6 ± 1.7) weeks, and birth weight of (2 950 ± 645) g. There were good correlation ( r=0.860, P<0.05) and consistency (95.1% of the samples fall within the 95% consistency interval) between IBB and TcB.Good correlation and consistency were also yielded in subgroup analyses based on the sex, age, gestational age and birth weight.The consistency was better in subgroups of ≤7 d, >37 weeks and>2 500 g. The ability of IBB to predict TcB>256.5 μmol/L was better than that of TcB>171.0 μmol/L.The area under the ROC curve was 0.93, the cut-off value was 232.6 μmol/L, the sensitivity was 96.7%, and the specificity was 82.6%.The difference of the mean values of IBB and TcB detected for 3 times was significantly lower than that obtained in the first measurement of IBB and TcB [(12.0 ± 34.4) μmol/L vs.(14.4 ± 38.6) μmol/L, P=0.038]. There were no adverse events and no defects in the device itself. Conclusions:There are good correlation and consistency between IBB and TcB.The ability of IBB to predict TcB>256.5 μmol/L is better than that of TcB>171.0 μmol/L, which is safe in clinical use.

Influences of Cell-ECM Adhesion on Migration of Tumor Cells Regulated by ECM Stiffness: A Model Study / 医用生物力学

Objective To study the influence of cell-extracellular matrix (ECM) adhesion on migration of tumor cells regulated by ECM stiffness. Methods The cellular Potts model (CPM) was established to simulate tumor cell growth and cellular immune feedback system. The effects from mechanical behavior of cells on cell-ECM adhesion were observed, and the migration of tumor cells under different ECM was analyzed. Results The ECM stiffness could influence the migration rate of tumor cells. The change of ECM stiffness regulated the adhesion force between cells and ECM, and the change of adhesion force would influence the migration rate of cells. Conclusions The migration and distribution patterns of cells are closely related to the adhesion and stiffness of ECM. The increase in ECM stiffness can effectively promote the migration rate of tumor cells, and the further increase in ECM stiffness inhibits the migration of tumor cells. These findings may further reveal dynamic changes of ECM, adhesion and mechanical performance of tumor cell migration.

miRNA-541-5p inhibits proliferation and migration of colon cancer cells by negatively regulating cyclin D1 / 肿瘤研究与临床

Objective:To investigate the effect of cyclin D1 (CCND1) negatively regulated by miRNA-541 (miR-541-5p) on the proliferation and migration of colon cancer cells as well as its related mechanism.Methods:Expression levels of miR-541-5p in colon cancer cell lines HT29, SW480, SW620, HCT116 and enterocyte line HIEC of the normal people as well as cancer tissues and pericarcinomatous normal tissues of 112 patients undergoing the colon cancer surgery from the First Affiliated Hospital of Hebei North University between April 2017 and March 2020 were detected by using quantitative real-time polymerase chain reaction(qRT-PCR). The potential target gene of miR-541-5p was predicted by using TargetScan, and was verified by using dual luciferase reporter gene assay, qRT-PCR and Western blot. Expression level of CCND1 was detected in colon cancer cell lines and tissues. Cells with the lowest expression level of miR-541-5p were divided into miR-NC group (the transfected control plasmid), miR-541-5p group (the transfected miR-541-5p mimics), miR-541-5p+CCND1 group (the co-transfected miR-541-5p mimics and CCND1). Effect of miR-541-5p and CCND1 on proliferation and migration ability of colon cancer cells was detected by using cell counting kit-8 (CCK8) and Transwell method. The xenograft model of colon cancer in nude mice was constructed to observe the effect of miR-541-5p on tumor growth.Results:The relative expression level of miR-541-5p in colon cancer tissues was lower than that in pericarcinomatous normal tissues (0.45±0.06 vs. 1.00±0.12, t = 43.385, P < 0.01). The relative expression level of miR-541-5p was 0.46±0.03, 0.67±0.04, 0.57±0.06, 0.17±0.02, 1.00±0.15, respectively in colon cancer cell lines HT29, SW480, SW620, HCT116 and enterocyte line HIEC of the normal people, and the difference was statistiacally significant ( F = 5.621, P < 0.01); the relative expression level of miR-541-5p in all colon cancer cell lines was lower than that in enterocyte line HIEC of the normal people. HCT116 cells were selected to make the subsequent experiments. The predicted results of TargetScan showed that 3'UTR of CCND1 might have sites complementary to those of miR-541-5p. Dual luciferase reporter gene assay showed that CCND1 was the target gene of miR-541-5p, and miR-541-5p negatively regulated the expression of CCND1. CCK-8 method showed that cell proliferation rate of HCT116 was (2.00±0.16)%, (0.89±0.08)%, (2.56±0.23)%, respectively in miR-NC group, miR-541-5p group, miR-541-5p+CCND1 group, and the difference was statistically significant ( F = 6.715, P < 0.01); among HCT116 cells with the overexpression of miR-541-5p, the transfected CCND1 chould reverse the inhibitory effect of miR-541-5p on cell proliferation. Transwell results showed that the overexpression of miR-541-5p inhibited the cell migration ability of HCT116, while the co-transfection of miR-541-5p mimics and CCND1 could reverse the inhibitory effect. In the colon cancer nude mice xenograft model, the tumor mass and size of nude mice in miR-541-5p group was decreased compared with that in the control group (all P < 0.05). Conclusions:miR-541-5p inhibits cell proliferation and migration of colon cancer cells via negatively regulating CCND1, and inhibits tumor growth in xenograft model of colon cancer in nude mice, thereby acting as a tumor suppressor in colon cancer.

Risk factors for neutropenia of late newborns / 中国当代儿科杂志

OBJECTIVE@#To study the risk factors and treatment for neutropenia of late newborns (NLN).@*METHODS@#Related clinical data were collected from the preterm infants and critically ill neonates who were admitted to the neonatal intensive care unit from July 2019 to January 2020. A total of 46 newborns with a blood absolute neutrophil count (ANC) of 37 weeks. There was no significant difference between the two groups in the incidence rates of gestational hypertension, premature rupture of membranes > 18 hours and intrauterine distress, 5-minute Apgar score, the duration of positive pressure ventilation, the incidence rate of early-onset sepsis, and the type of initially used antibiotics (@*CONCLUSIONS@#The risk of NLN increases with the presence of late-onset sepsis and the increase in the duration of antibiotic use. NLN is generally a benign process. G-CSF appears to be safe and effective for NLN with severe disease conditions or severe reduction in ANC.

Protective effects of Dendrobium officinale superfine powder against LPS-induced intestinal mucosal injury in mice / 中国中药杂志

This study aims to investigate the preventive effect of Dendrobium officinale in LPS-induced intestinal mucosal damage. Forty SPF-grade C57 BL/6 J male mice were randomly divided into normal group(NC), model group(LPS), and two superfine powder groups of Dendrobium officinale(DOF)(DOF-L, 0.30 g·kg~(-1)and DOF-H, 0.60 g·kg~(-1), respectively), with 10 mice in each group. DOF superfine powder suspension was given via oral administration to mice for 7 days, while the mice in NC and LPS groups received the same volume of saline for 7 days. On the eighth day, the mice in LPS group and DOF treatment groups were injected with LPS(5 mg·kg~(-1)) by intraperitoneal injection to establish the intestinal mucosal injury model, while the mice in NC group were injected with the same volume of sterile saline in the same manner. Six hours after injection with LPS or saline, plasma and the intestinal tissue were collected. The diamine oxidase(DAO) and D-lactate levels in plasma were detected with a biochemical method. The levels of proinflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in plasma were detected by ELISA. The histomorphology and ultrastructure of mouse ileum tissues were observed by hematoxylin-eosin(HE) staining in optical microscope and transmission electron microscope(TEM). The expression and distribution of tight junction(TJ) proteins claudin-1, occludin and F4/80 were detected by immunohistochemistry while the protein expression levels of Toll-like receptor 4(TLR-4) and nuclear factor kappa B p65(NF-κB p65) in jejunum were detected by Western blot. The experimental results showed that continuous intragastric administration of D. officinale superfine powder for 7 days obviously alleviated the damage and ultrastructural changes of intestinal mucosa induced by LPS; significantly decreased DAO and D-lactate levels in plasma in model group(P<0.05); up-regulated the protein expression of claudin-1 and occludin in ileum tissues; down-regulated the protein expression of TLR-4 and NF-κB p65 in jejunum tissues(P<0.01); significantly decreased TNF-α and IL-6 levels in plasma(P<0.05); and decreased the infiltration of F4/80~+ macrophage cells. Our results suggested that D. officinale had significant protective effects on LPS-induced intestinal mucosal damage and reduced intestinal permeability. The mechanism might be related to its effects of inhibiting inflammation via TLR-4/NF-κB p65, and up-regulating the expression of tight junction proteins.