Objective:To study the effect of different doses of oxycodone on the serum thromboxane A2 (TXA2),plasma endothelin (ET) levels and immune function of patients underwent laparoscopic cholecystectomy.Methods:90 patients of elective laparoscopic cholecystectomy who were treated from August 2013 to August 2016 in our hospital were selected and divided into 3 groups by random number table,with 30 cases in each group.At the beginning of operation,they were given intravenous oxycodone,group A was given 0.1 mg/kg oxycodone,group B was given 0.2 mg/kg oxycodone,group C was given 0.3 mg/kg oxycodone.The changes of hemodynamics,serum TXA2 and ET levels were compared between the three groups at T0 (after admission),T1 (after anesthesia induction),T2 (after intubation),T3 (gallbladder separation),T4 (end of surgery) and the changes of immune function was compared at T0,T5 (postoperative 2h),T6(postoperative 1d),T7 (postoperative 3d);and the extubation time,recovery time,hypotensor,additional analgesics situationin and adverse reactions were recorded.Results:The diastolic pressure (DBP),systolic blood pressure (SBP),heart rate (HR) in three groups at T2,T3 point was significantly higher than T0 point(P＜0.05),the DBP,SBP and HR in the B,C groups were significantly lower than the A group at T2 and T3 point(P＜0.05);the TXA2 in three groups at T2,T3,T4 point was significantly higher than T0 point(P＜0.05),and A group＞B group＞C group,there was significant difference between the two groups (P＜0.05);the ET in three groups at T2,T3 point was significantly higher than T0 point(P＜0.05),the ET in the B,C group was significantly higher than the A group at T2,T3 point(P＜ 0.05);the CD3+,CD4+,CD8+ and CD4+/CD8+ of the three groups at T5 point were significantly lower than that ofT0 point (P＜0.05),the CD3+,CD4+,CD8+ and CD4+/CD8+ in A group were significantly lower than that of B,C group at T5 point (P＜0.05);the extubation time in C group was significantly longer than that of A,B group(P＜0.05);the total incidence of adverse reactions in C group was significantly higher than that the A,B group (P＜0.05).Conclusion:In the laparoscopic cholecystectomy,application of 0.2 mg/kg oxycodone had little effect on hemodynamics,serum TXA2,ET levels and immune function with higher safety.

Objective To compare the clinical efficacy and safety of agomelatine and paroxetine for the senile depression. Methods A total of 98 cases of elderly patients diagnozed with depression were randomly divided into two groups, one group were treated with agomelatine,the other group were treated with paroxetine,treated for 6 weeks, using Hamilton depression scale(HAMD), adverse reaction scale(TESS) to evaluate the efficacy and adverse reactions. Results After 6 weeks of treatment, the HAMD scores showed that there were no significant differences in clinical efficacy of two groups, and the TESS showed the agomelatine had less adverse reaction than the paroxetine. Conclusion Agomelatine is a safe and effective antidepressant , suitable for elderly patients.

Objective:To analyze the results of ATP7B gene screening in neonates and explore the linkage disequilibrium between different mutation loci, providing a basis for the clinical diagnosis and genetic counseling of Wilson′s disease.Methods:A total of 12 619 newborns who were born in Women′s Hospital of Nanjing Medical University during March 18 and December 30, 2022, including 6 605 male neonates and 6 014 female neonates, with birth weight of (3.44±0.56) kg, were retrospectively collected. The results of ATP7B gene screening in all newborns were analyzed.Next-generation sequencing technology was employed to detect the pathogenic loci of ATP7B gene, and the identified loci were verified using Sanger sequencing. PLINK 1.9 software was used to analyze the linkage disequilibrium of different mutation loci.Results:Among 12 619 neonates, 22 cases were diagnosed with 2-3 pathogenic mutations in the ATP7B gene (suspected positive). Among them, 20 cases were recalled for family verification, and 2 cases refused to recall. The verification results showed that 3 newborns had mutations of two loci respectively from their parents and were preliminarily diagnosed with Wilson′s disease, the other 17 neonates were carriers of the c.3316G>A/c.588C>A or c.1708-1G>C/c.1168A>G mutation loci arranged in a cis-acting manner from the father source or maternal source. A total of 249 pathogenic mutation carriers were detected (232 cases carrying 1 pathogenic mutation, and 17 cases carrying 2 pathogenic mutations), with a carrier rate of 1/51. Among them, the mutation c.2333G>T was most frequently detected (1/207), followed by c.2975C>T (1/421), c.2621C>T (1/742), c.2755C>G (1/971) and c.2605G>A (1/971). The results of linkage disequilibrium analysis in both c.3316G>A/c.588C>A and c.1708-1G>C/c.1168A>G showed that D ′=1, which showed complete linkage disequilibrium. Conclusion:The carrier rate of pathogenic mutations in the ATP7B gene is relatively high.Moreover, the c.3316G>A/c.588C>A and c.1708-1G>C/c.1168A>G pathogenic mutation loci are likely to be arranged in a cis-acting manner, highlighting the existence of linkage disequilibrium between the two groups of mutations. This finding provides important reference value for the clinical diagnosis and genetic counseling of Wilson disease.

Background and objective Th17 cells are important T helper cells, which are characterized by their production of IL-17. hT17 cells play an important role in host defense against microbial infections, autoimmune diseases and cancer. hTe aim of this study is to investigate the percentage of hT17 in peripheral blood lymphocyte and the level of IL-17 in serum and cerebrospinal lfuid (CSF) in patients with brain metastases from lung cancer. Methods Twenty-two patients with brain metastases from lung cancer and 20 health controls were analyzed. hTe percentage of hT17 cell was detected with lfow cytometry using CD3+CD4+IL-23R+marker, the level of IL-17 was measured with ELISA method. Results hTe percentage of hT17 cells in patients with brain metastases from lung cancer was 4.65%±0.72%, which was remarkably higher than that in con-trols (2.71%±0.54%, P=0.04). hTere was no signiifcant difference between non-small cell lung cancer (NSCLC) patients and small cell lung cancer (SCLC) patients. Serum IL-17 was remarkably increased in patients with brain metastases from lung can-cer (117.4±16.43 pg/mL vs 72.55±8.19 pg/mL, P=0.02). No signiifcant difference of the serum IL-17 was observed between NSCLC and SCLC patients. hTe level of IL-17 in CSF from patients with brain metastases from lung cancer was signiifcant higher than that from lung cancer patients without brain metastases (73.21±7.52 pg/mL vs 50.25±8.04 pg/mL, P=0.04). Con-clusion hT17 cells and IL-17 increase in patients with brain metastases from lung cancer. It may involve in the pathogenesis of brain metastases from lung cancer.

Objective To study the clinical value of enhanced recovery after surgery (ERAS) in the perioperative treatment of type Ⅰ (Todami,1975) biliary dilatation (BD) of children.Methods To retrospectively analyze the data of children with type Ⅰ BD who were treated in the General Surgery Department of Zhengzhou Children's Hospital from June 2014 to May 2018.A total of twenty children with type Ⅰ BD treated with ERAS and 20 children treated with the traditional method in our department were selected in this study using the random number table method.Postoperative indicators (including operation time,first defecation time,changes in amylase in blood and abdominal cavity exudates,length of hospital stay,and hospitalization fee) and relevant postoperative complications (including sore throat,nausea and vomiting,urethral pain,upper respiratory tract infection,incision wound infection,adhesive intestinal obstruction,anastomotic leakage and pancreatic fistula) of the ERAS group and the control group were compared.Results The first defecation time,length of hospital stay and hospitalization fee were significantly lower in the ERAS group than the control group (all P ＜ 0.05) [first defecation time (1.98 ± 0.25) d vs.(2.25 ± 0.31) d;length of hospital stay (6.91 ± 1.25) d vs.(9.95 ± 1.53) d;hospitalization fee (23.32 ± 2.25)thousand yuan vs.(25.99 ±3.10) thousand yuan].Moreover,the incidences of sore throat,nausea and vomiting,urethral pain and upper respiratory tract infection were significantly lower in the ERAS group than the control group (all P ＜ 0.05) [the incidences of sore throat (5.0％ vs.45.0％);the incidences of sickness and vomiting (5.0％ vs.30.0％);the incidences of urethral pain (5.0％ vs.45.0％);the incidences of upper respiratory tract infection (5.0％ vs.40.0％)].On the other hand,there were no significant differences in the mean operation times,changes in amylase levels in the blood or abdominal cavity exudates,incision wound infection,and incidences of adhesive intestinal obstruction,anastomotic leakage and pancreatic fistula (all P ＞ 0.05).Conclusions ERAS for type Ⅰ BD surgery was safe and reliable in children.It effectively promoted recovery of postoperative gastrointestinal function and reduced the incidence of complications.

Objective:To establish the cut-off value of tetradecenoyl carnitine (C14∶1)/dodecenoyl carnitine(C12∶1) based on non-derivatized tandem mass spectrometry (MS/MS), and to explore the application value of C14∶1/C12∶1 to screen newborns for very long chain acyl-CoA dehydrogenase deficiency (VLCADD), determining the best combination of indicators for screening VLCADD.Methods:This retrospective study included data from 17 newborns with VLCADD detected by MS/MS and confirmed by acyl-CoA dehydrogenase very long chain ( ACADVL) gene detection, and 423 507 newborns with normal MS/MS results. The data from these newborns were collected from January 2014 to December 2021 as the newborns received neonatal screening in Nanjing Neonatal Disease Screening Center and Suzhou Neonatal Disease Screening Center. All newborns were divided into 3 groups: all newborns group, full-term newborns group and normal-birth-weight newborns group, and the cut-off values of C14∶1/C12∶1 for VLCADD in these 3 groups were determined by their receiver operating characteristic (ROC) curves individually. With these results, a total of 5 interpretation schemes were composed using different indicators alone or jointly: scheme 1 being C14∶1/C12∶1, scheme 2 being C14∶1, scheme 3 being C14∶1+C14∶1/C2+C14∶1/C16, scheme 4 being C14∶1/C12∶1+C14∶1, and scheme 5 being C14∶1/C12∶1+C14∶1+C14∶1/C2+C14∶1/C16. The detection rate, false-positive rate and positive predictive value of each scheme were calculated, and their screening efficiencies were statistically compared by Chi-square tests. Results:The cut-off values of C14∶1/C12∶1 for VLCADD in the 3 newborn groups were all 2.80. The detection rates of VLCADD with all 5 interpretation schemes were 17/17. Scheme 1 had the highest false positive rate [26.15‰ (11 075/423 524)] and the lowest positive predictive value [0.15% (17/11 092)]. Scheme 4 (Scheme 5) had the lowest false positive rate [0.02‰ (10/423 524)] and the highest positive predictive value [62.96% (17/27)]. Comparing scheme 4 (Scheme 5) with scheme 1, scheme 2 and scheme 3, the differences of false positive rate (χ2=302.30,11 191.50,32.06) and positive predictive value (χ2=102.51,3 485.61,13.83) were statistically significant (all P<0.001). Conclusion:C14∶1/C12∶1 was an effective auxiliary interpretive indicator for VLCADD in newborn screening, and the combination of C14∶1/C12∶1+C14∶1 was tested to be the best indicator for VLCADD screening based on non-derivatized tandem mass spectrometry.

Clinical data of 166 children with Meckel's diverticulum, who were treated with laparoscopic surgery in our center from January 2015 to January 2023, were retrospectively analyzed, including 69 cases receiving enhanced recovery after surgery (ERAS group) and 97 cases with traditional perioperative care (control group). There were no significant differences in age ( t=1.391), gender ( χ2=1.067), body weight ( t=1.182 ), operation time ( t=1.093), diverticulum location ( Z=0.405), surgical procedures ( χ2=0.053), and intraoperative blood loss ( t=0.394) between two groups (all P>0.05). Compared to control group, ERAS group had shorter time for indwelling gastric tube (1.1±0.7 d vs.3.8±0.8 d), earlier postoperative feeding (2.5±0.6 d vs.4.9±0.7 d), less intravenous fluid infusion (3.9±1.0 d vs. 5.3±1.1 d), shorter length of hospital stay (8.2±1.6 d vs.10.9±2.3 d), and lower hospitalization expenditure (1.8±0.2)×10 4 yuan vs. (2.1±0.3)×10 4 yuan ( t=23.289,21.718,8.505,8.379,8.769,all P<0.05). There was no significant difference in incidence of postoperative complications between two groups ( χ2=0.431, P>0.05). The study indicates that patients treated with ERAS programmed laparoscopic Meckel's diverticulum surgery is safe and effective with rapid recovery and shorter hospital stay.

Objective:To understand the regional prevalence and hotspot mutations through analysis of genetic screening results for newborns with pseudohypertrophic muscular dystrophy.Methods:A total of 22 813 newborns (12 065 males and 10 748 females) born at the Women's Hospital of Nanjing Medical University from March 18, 2022, to October 31, 2023, were selected. The Dystrophin gene ( DMD) was detected using chip capture next-generation sequencing technology, followed by bioinformatics analysis. Pathogenic mutations identified were validated using multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. Serum creatine kinase levels were also tested in suspected male patients. Descriptive analysis was applied for this study. Results:Among the 10 748 girls, 14 carriers of DMD gene were detected (0.013%), of which, nine cases were validated in the family; one case was a de novo mutation, five were inherited from the mother, and three were inherited from the father. The screening identified nine suspected patients among the boys (0.075%), and eight of them were confirmed by family validation, in which three were de novo mutations, and five were inherited from the mother. Among all identified DMD mutations, deletions were the most common one, accounting for 52.2% (12/23), incluling four cases of deletion at 49-51 exon. Conclusions:Newborn genetic screening based on chip capture next-generation sequencing technology combined with bioinformatics analysis is helpful in early detection of patients and carriers of pseudohypertrophy muscular dystrophy. According to the preliminary statistics, the incidence rate of DMD/BMD in this area is 1/1 341 male infants and the hotspot mutation is exon 49 to 51 deletion.

In recent years, the genome editing technologies based on the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) have developed rapidly. The system can use homologous directed recombination (HDR) to achieve precise editing that it medicated, but the efficiency is extremely low, which limits its application in agriculture and biomedical fields. As an emerging genome editing technology, the CRISPR/Cas-mediated DNA base editing technologies can achieve targeted mutations of bases without generating double-strand breaks, and has higher editing efficiency and specificity compared with CRISPR/Cas-mediated HDR editing. At present, cytidine base editors (CBEs) that can mutate C to T, adenine base editors (ABEs) that can mutate A to G, and prime editors (PEs) that enable arbitrary base conversion and precise insertion and deletion of small fragments, have been developed. In addition, glycosylase base editors (GBEs) capable of transitioning from C to G and double base editors capable of editing both A and C simultaneously, have been developed. This review summarizes the development, advances, advantages and limitations of several DNA base editors. The successful applications of DNA base editing technology in biomedicine and agriculture, together with the prospects for further optimization and selection of DNA base editors, are discussed.
Agriculture ; CRISPR-Cas Systems/genetics* ; DNA/genetics* ; Gene Editing ; Technology

PURPOSE: Details of patients hospitalized for asthma exacerbation in mainland China are lacking. To improve disease control and reduce economic burden, a large sample survey among this patient population is indispensable. This study aimed to investigate the clinical characteristics and outcomes of such patients.METHODS: A retrospective study was conducted on patients hospitalized for asthma exacerbation in 29 hospitals of 29 regions in mainland China during the period 2013 to 2014. Demographic features, pre-admission conditions, exacerbation details, and outcomes were summarized. Risk factors for exacerbation severity were analyzed.RESULTS: There were 3,240 asthmatic patients included in this study (57.7% females, 42.3% males). Only 28.0% used daily controller medications; 1,287 (39.7%) patients were not currently on inhaled corticosteroids. Acute upper airway infection was the most common trigger of exacerbation (42.3%). Patients with severe to life-threatening exacerbation tended to have a longer disease course, a smoking history, and had comorbidities such as hypertension, chronic obstructive pulmonary disease (COPD), and food allergy. The multivariate analysis showed that smoking history, comorbidities of hypertension, COPD, and food allergy were independent risk factors for more severe exacerbation. The number of patients hospitalized for asthma exacerbation varied with seasons, peaking in March and September. Eight patients died during the study period (mortality 0.25%).CONCLUSIONS: Despite enhanced education on asthma self-management in China during recent years, few patients were using daily controller medications before the onset of their exacerbation, indicating that more educational efforts and considerations are needed. The findings of this study may improve our understanding of hospital admission for asthma exacerbation in mainland China and provide evidence for decision-making.
Adrenal Cortex Hormones ; Asthma ; China ; Comorbidity ; Disease Progression ; Education ; Female ; Food Hypersensitivity ; Hospitalization ; Humans ; Hypertension ; Inpatients ; Medication Adherence ; Mortality ; Multivariate Analysis ; Pulmonary Disease, Chronic Obstructive ; Retrospective Studies ; Risk Factors ; Seasons ; Self Care ; Smoke ; Smoking