Objective:To investigate the effects of birth intervals on maternal and infant outcomes in pregnant women with gestational diabetes mellitus (GDM).Methods:This retrospective study recruited 445 pregnant women with GDM who received prenatal examinations and delivered in Peking University First Hospital-Ningxia Women Children's Hospital from January 2020 to December 2021. Based on the birth interval classification standard recommended by WHO and the American College of Obstetricians and Gynecologists, these subjects were divided into three groups: shorter group (<18 months, n=69), normal group (18-59 months, n=213) and longer group (≥60 months, n=163). Analysis of variance, Chi-square test, and multivariate logistic regression model were used for statistical analysis. Results:There were statistically significant differences in the maternal age at this and previous pregnancy [(30.6±4.1), (30.8±3.8) vs (32.7±3.7) years; (22.7±2.4), (26.3±2.9) vs (29.9±4.1) years] and the incidence of oligohydramnios [10.1% (7/69), 1.9% (4/213) vs 3.1% (5/163)] and preterm birth [14.5% (10/69), 5.2% (11/213) vs 1.8% (3/163)] between the shorter, normal, and longer groups (all P<0.05). After adjusting for confounding factors in the present pregnancy, the risks of oligohydramnios, preterm birth, and low birth weight increased in the shorter group [ OR (95% CI): 4.73 (1.75-12.85), 5.54 (1.37-22.42) and 9.54 (3.05-29.82), all P<0.05] and so did the risk of postpartum hemorrhage in the longer group [ OR (95% CI): 4.45 (1.72-11.49), P<0.05]. Conclusions:Both longer and shorter birth intervals can affect maternal and infant outcomes of GDM patients. Postpartum healthcare should be strengthened for GDM patients who desire more children to help them maintain an appropriate birth interval, thus promoting maternal and infant health.

This article introduces the mechanism including antigen presentation, adjuvant, lymphatic system and the characteristics of vaccine, and then summarizes the key applications of core pharmacometrics approaches including QSP, PK/PD, dose response analysis, MBMA, in dose-response, preclinical and clinical translation, and correlation between biomarkers and efficacy of vaccines. It is expected that the successful application of model informed drug development can promote model informed vaccine development so that pharmacometrics makes its due contributions to the development of safer, more effective and more controllable vaccine products.

Objective:To analyze the clinical characteristics, examination results, treatment and prognosis of neonates with influenza virus infection in the neonatal intensive care unit (NICU).Methods:Clinical data of neonates with influenza virus infection who were hospitalized in the NICU of the General Hospital of Southern Theater Command of Chinese People′s Liberation Army from January 2018 to December 2020 were retrospectively analyzed.Results:A total of 11 hospitalized neonates with influenza virus infection in the NICU were recruited, including 2 cases of influenza A and 9 cases of influenza B. Ten cases (90.9%) had respiratory symptoms, and among them, there were 8 cases with increased oxygen demand, 7 cases with complicated pneumonia, 4 cases with dyspnea, and 2 cases with apnea.Seven cases showed abnormal body temperature, including 6 cases of fever, and 1 case of hypothermia.Five cases had circulatory system symptoms.Digestive system symptoms and urinary system symptoms were detected in 5 cases and 3 cases, respectively.Eight cases complicated with systemic symptoms, including 3 cases of poor mental response, 3 cases of worsening jaundice, 3 cases of weight loss, 2 cases of hyperglycemia, 1 case of edema and sclerosis.Ten cases were treated with gamma globulin immunotherapy, 2 cases were treated with plasma immune support, and 1 case was treated with Peramivir antiviral.Eight cases were treated with increased oxygen therapy, among which non-invasive ventilator parameters or modes increased in 4 cases, and nasal cannula oxygen concentration increased in 2 cases.The change of noninvasive-assisted ventilation to invasive-assisted ventilation occurred in 1 case, and 1 case developed the change of nasal cannula to noninvasive-assisted ventilation.Four neonates received anti-shock and (or) myocardial contractility therapy.Conclusions:Neonates with influenza virus infection in the NICU are mainly manifested as respiratory symptoms and fever, and the incidence of complicated pneumonia is high.Multiple systems may be involved at the same time, often leading to severe disease status.Comprehensive supportive treatment is necessary.Neonatologists should pay attention to these symptoms, and early detection of influenza virus and timely isolation are the key methods to prevent influenza outbreaks in NICU.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.

Objective: To analyze the impact of dual antiplatelet (DAPT) therapy combining with or without proton pump inhibitors (PPI) on the main outcomes after percutaneous coronary intervention (PCI). Methods: The PubMed, EMBASE and Cochrane Library were searched for relevant literature and the references obtained from these sources were retrieved manually from inception till September 2017. Inclusion and exclusion criteria were established follow the Cochrane review standard. A total of 977 literatures were included, 193 duplicates were excluded, 74 reviews, case reports, letters and systematic reviews were excluded, 667 literatures were excluded after reading the title and abstract, 34 literatures were excluded due to non-randomized control studies and unrelated outcome indicators, and 9 literatures were finally included with a total of 16 589 patients. RevMan 5.3 software was used to compare the incidence of major adverse cardiovascular events (MACE), cardiogenic death, recurrent myocardial infarction, target vessel revascularization, all-cause death, stent thrombosis, stroke, gastrointestinal bleeding and gastrointestinal events in patients with DAPT combining with or without PPI after PCI. Results: MACE was observed in 8 out of the 9 included literatures, and the results showed that MACE occurred in 561 out of 6 282 patients receiving DAPT combining with PPI therapy and in 951 out of 9 632 patients using DAPT alone (OR=1.15, 95%CI 0.88-1.51, P>0.05). Cardiogenic death was observed in 7 out of the 9 included literatures, and the results showed that cardiogenic death occurred in 172 out of 6 453 patients receiving DAPT combining with PPI treatment and in 321 out of the 9 839 patients using DAPT alone (OR=0.97, 95%CI 0.80-1.18, P>0.05). Recurrent myocardial infarction was observed in 7 out of the 9 included literatures, the results showed 416 out of 6 282 cases in DAPT combining with PPI therapy group experienced recurrent myocardial infarction and 691 out of 9 632 cases in DAPT group experienced recurrent myocardial infarction (OR=1.01, 95%CI 0.89-1.16, P>0.05). Four out of 9 literatures observed revascularization. The results showed that revascularization was performed in 64 out of 2 173 patients receiving DAPT combining with PPI therapy and in 105 out of the 2 770 patients using DAPT alone (OR=1.33, 95%CI 0.55-3.24, P>0.05). All-cause death was observed in 7 out of the 9 included literatures, and the results showed that all-cause death occurred in 172 out of the 6 453 patients in DAPT combining with PPI therapy group and in 321 out of the 9 839 patients using DAPT alone (OR=0.97, 95%CI 0.80-1.18, P>0.05). Three out of the 9 included articles observed stent thrombosis, and the results showed that stent thrombosis occurred in 99 out of 2 997 patients receiving DAPT combining with PPI therapy and in 245 out of the 6 198 patients treated with DAPT (OR=1.07, 95%CI 0.83-1.37, P>0.05). Stroke was observed in 2 out of the 9 included literatures. The results showed that stroke occurred in 5 out of 2 019 patients receiving DAPT combining with PPI therapy, and in 4 out of the 2 033 patients treated with DAPT (OR=1.00, 95%CI 0.29-3.49, P>0.05). Gastrointestinal bleeding was observed in 6 out of the 9 included literatures. The results showed that gastrointestinal bleeding occurred in 26 out of 3 517 patients receiving DAPT combined with PPI therapy, and in 93 out of the 3 506 patients treated with DAPT, gastrointestinal bleeding was significantly lower in the DAPT combining with PPI group than DAPT alone group (OR=0.27, 95%CI 0.17-0.41, P<0.01). Gastrointestinal events were reported in 6 out of the 9 included articles. Similarly, gastrointestinal events were observed in 51 out of 3 517 patients receiving DAPT combined with PPI therapy, and in 190 out of the 3 506 patients treated with DAPT alone, the incidence of gastrointestinal events in the DAPT combined with PPI group was significantly lower than DAPT alone group (OR=0.24, 95%CI 0.14-0.42, P<0.01). Conclusions The incidence of MACE, cardiogenic death, recurrent myocardial infarction, target vessel revascularization, all-cause death, stent thrombosis and stroke are not affected by DAPT combined with PPI therapy after PCI, while the incidence of gastrointestinal bleeding and gastrointestinal events could be reduced by adding PPI to DAPT in patients undergoing PCI.

Objective To explore the factors influencing serum trough concentration of vancomycin in pediatric patients with severe gram-positive cocci pneumonia. Methods The general information, the biochemical test results, and plasma concentration of vancomycin were collected from 93 pediatric patients with severe gram-positive cocci pneumonia. The relative factors influencing trough concentration of vancomycin were analyzed retrospectively. Results With the dosage of 40-60 mg/(kg·d), serum trough concentration of vancomycin were between 10-20 mg/L in 26 patients, <10 mg/L in 54 cases, ≥20 mg/L in 13 cases. The ALT, AST, GFR, and γ-GT were significantly different among three groups (P<0.05); the 10-20 mg/L group had the highest levels of AST and γ-GT, the ≥20 mg/L group had the highest level of ALT and the lowest level of GFR. Multiple linear regression analysis showed that GFR was negatively linearly correlated with the serum trough concentration of vancomycin (R2=0.039, P<0.05). The median serum trough concentration of vancomycin in pediatric patients with GFR≥90, 60–90, 30–60 mL/(min·1.73m2) were 8.66, 18.21, 8.45 mg/L respectively, and the difference is statistically significant (P<0.05). Conclusions The serum trough concentration of vancomycin is negatively linearly correlated with GFR in pediatric patients with severe gram-positive cocci pneumonia. The patients with impaired renal function are easier to reach the target serum trough concentration of vancomycin. Clinical use of vancomycin should follow the low doses in the range the guideline recommended, and the serum trough concentration should be closely monitored.

Objective To explore the mechanism of tripterygium wilfordii polyglycoside tablets for elderly patients with relapsing refractory immune thrombocytopenic purpura (ITP),and to seek the theoretical basis for Chinese medicine treatment of this disease.Methods The clinical data of 79 patients with relapsing refractory ITP were retrospectively analyzed.According to whether the combined use of tripterygium wilfordii polyglycoside,they were divided into the control group (35 cases) and the observation group (44 cases).The control group was treated with platelet and tranexamic acid,sulfasalazine,sulforaphane sodium,hemagglutinin and other symptomatic hemostasis treatment.The observation group in symptomatic hemostasis support on the basis of treatment with tripterygium wilfordii polyglycoside tablets.The CD4+/CD8+ ratio and CD4+ CD25+ Treg expression were compared between the two groups.Results The CD4+/CD8+ ratio,CD4+ CD25+ Treg and platelet count in the control group before treatmentwere (0.96 ± 0.36),(1.21 ± 0.67) ％,(13.14 ± 6.92) × 109/L,respectively,which of the observation group were (0.92 ± 0.37),(1.19 ± 0.59) ％,(11.51 ± 6.21) × 109/L,respectively,there were no statistically significant differences between the two groups (all P ＞ 0.05).The CD4+/CD8+ ratios in peripheral blood of the observation group at 2 weeks,3 weeks and 4 weeks after treatmentwere (1.04 ±0.56),(1.55 ±0.34),(1.59 ±0.41),respectively,there were statistically significant differences between the two groups (t =9.994,9.797,all P ＜ 0.05).The CD4+ CD25+ Treg proportions in the observation group at 2 weeks,3 weeks and 4 weeks after treatmentwere (1.01 ± 0.61) ％,(1.06:±:0.57) ％,(5.92 ± 0.65) ％,respectively,there was statistically significant difference between the 4 weeks after treatment and before treatment(t =5.378,P ＜ 0.05).The CD4+/CD8+ ratios in the peripheral blood of the control group were (1.01 ±0.60),(0.89 ±0.50) and (0.96 ±0.51),respectively,and the CD4+ CD25+ Treg in control group at 2 weeks,3 weeks and 4 weeks after treatment proportions were (0.99 ±0.72)％,(1.15 ±0.66)％,(1.22 ±0.56)％,respectively,there were no statistically significant differences between before and after treatment (all P ＞0.05).There were statistically significant differences in the CD4+/CD8+ ratio and CD4+ CD25+ Treg expression between the observation group and control group at 4 weeks after treatment (t =8.589,P ＜ 0.01;t =2.369,P ＜ 0.05).There was no statistically significant difference in the platelet count between the two groups(P ＞ 0.05),but the symptoms of bleeding of the observation group was lighter at 3 weeks after treatment.Conclusion Tripterygium wilfordii polyglycoside improves the expression of CD4+/CD8+ and CD4+ CD25+ Treg in peripheral blood of elderly patients with relapsed or refractory ITP.It is an ideal drug for the treatment of relapsed and refractory ITP in the elderly,it is worth further study.

Objective To investigate the status of medication adherence of secondary prevention after acute ischemic stroke and influence on prognosis in Qingdao area , including antithrombotic drugs , lipid-lowering drugs , antihypertensive drugs and glucose-lowering drugs , to provide the basis for making medical policy.Methods We examined patients with acute cerebral infarction and transient ischemic attack in the Department of Neurology of Affiliated Hospital of Qingdao University from December 2014 to January 2016.Patients′medication status and recurrence of stroke events were registered by using telephone and clinic follow-up within six months after the patients discharged from hospital .The standard of good and bad drug adherence was as follows:good adherence was defined as proportion of days covered ( PDC) ≥80%, bad adherence was defined as PDC <80%.SPSS 19.0 statistical software was used to analyze the influence factors of medication adherence and the influence of medication adherence on prognosis .Results Finally, 444 cases (88.62%) were analyzed.A total of 352 cases (79.28%) had high medication adherence at six months after discharging from hospital .The following factors can improve the adherence of drug treatment:history of diabetes (108 cases (30.68%) in good medication adherence group , 16 cases (17.39%) in poor medication adherence group,χ2 =6.401, P=0.011), having employee health insurance (186 cases (52.84%) in good medication adherence group , 33 cases (35.87%) in poor medication adherence group ,χ2 =8.405, P=0.004), endovascular stent implantation (29 cases(8.24%) in good medication adherence group, 0 case in poor medication adherence group ,χ2 =8.109, P=0.004), staying in hospital more than 10 days ( 230 cases ( 65.34%) in good medication adherence group , 49 cases ( 53.26%) in poor medication adherence group ,χ2 =4.558, P=0.033).Six months later , the modified Rankin Scale ( mRS) score of poor medication adherence group was significantly higher than that in good adherence group ( mRS score≥3,50 cases (14.20%) in good medication adherence group , 22 cases (23.91%) in poor medication adherence group,χ2 =5.060, P=0.024) .After six months, a total of 13 cases had recurrent cerebral infarction, with two cases ( 0.57%) in good adherence group , 11 cases ( 11.96%) in poor adherence group.High medication adherence was an independent protective factor of recurrent stroke ( OR=0.042, 95%CI 0.008 -0.210, P<0.01 ) .At one, three, six months after discharging from hospital , the medication adherence of antihypertensive and glucose-lowering drugs was better than that of antiplatelet agents and lipid-lowering drugs (all P<0.05).Conclusions The persistence and adherence to secondary preventive medication in ischemic stroke patients was generally well at 6th month after discharging from hospital.History of diabetes , having employee health insurance , stent implantation and longer hospital stay are the influencing factors to high medication adherence .High medication adherence is an independent protective factor for ischemic stroke recurrence .The medication adherence of antihypertensive and glucose-lowering drugs is better than that of antithrombotic drugs and lipid-lowering drugs.

Objective To compare the clinical efficacy of subinguinal microsurgical and single -port laparoscopic high ligation in the treatment of varicocele.Methods 218 patients with varicocele were enrolled in this study.According to the digital table,they were randomly divided into two group.148 cases were treated by subinguinal microscopic varicocelectomy(microscopic group),70 cases were treated by single -port laparoscopic high ligation varicocele(single -port laparoscopic group).Postoperative follow up was 3 -24months.The operative duration,length of hospital stay,hospitalization expense,postoperative complications and semen quality parameters were compared between the two groups.Results There were statistically significant differences in operative duration and hospitalization expense between the two groups(all P <0.05).There was no statistically significant difference in length of hospital stay (P >0.05).In the 218 followed -up patients,the sperm concentration and motility (grade a + b sperm)all significantly improved,which of the microscopic group and single -port laparoscopic group preoperation were (19.1 ± 8.2)×106 /mL,(18.2 ±7.9)×106 /mL and (22.7 ±7.8)%,(21.6 ±8.9)% respectively,which at 3 -6 months after operation were (56.2 ±10.8)×106 /mL,(45.8 ±12.9)×106 /mL and (58.8 ±9.7)%,(44.6 ±10.7)%, there were statistically significant differences compared with preoperation (t =6.227,9.579,all P <0.05 ). Conclusion The surgical methods in the treatment of varicocele can improve the quality of patients,but microscopic group is obviously better than single -port laparoscopic group in improvement of semen quality parameters,safety, patient -based compliance and economy.