PET/CT study of dopamine transporter (DAT) binding with the triple reuptake inhibitor toludesvenlafaxine in rats and humans.

PURPOSE: Toludesvenlafaxine is a recently developed antidepressant that belongs to the triple reuptake inhibitor class. Despite the in vitro evidence that toludesvenlafaxine inhibits the reuptake of serotonin (5-HT), norepinephrine (NE) and dopamine (DA), there is no in vivo evidence that toludesvenlafaxine binds to DAT and increases DA level, a mechanism thought to contribute to its favorable clinical performance. METHODS: Positron emission tomography/computed tomography (PET/CT) was used to examine the DAT binding capacity in healthy rats and human subjects and microdialysis was used to examine the striatal DA level in rats. [18F]FECNT and [11C]CFT were used as PET/CT radioactive tracer for rat and human studies, respectively. RESULTS: In rats, 9 mg/kg of toludesvenlafaxine hydrochloride (i.v.) followed by an infusion of 3 mg/kg via minipump led to the binding rate to striatum DAT at 3.7 - 32.41% and to hypothalamus DAT at 5.91 - 17.52% during the 45 min scanning period. 32 mg/kg oral administration with toludesvenlafaxine hydrochloride significantly increased the striatal DA level with the AUC0 - 180 min increased by 63.9%. In healthy volunteers, 160 mg daily toludesvenlafaxine hydrochloride sustained-release tablets for 4 days led to an average occupancy rates of DAT at 8.04% ± 7.75% and 8.09% ± 7.00%, respectively, in basal ganglion 6 h and 10 h postdose. CONCLUSION: These results represent the first to confirm the binding of toludesvenlafaxine to DAT in both rats and humans using PET/CT, and its elevation of brain DA level, which may help understand the unique pharmacological and functional effects of triple reuptake inhibitors such as toludesvenlafaxine. GOV IDENTIFIERS: NCT05905120. Registered 14 June 2023. (retrospectively registered).

Patterns of yeast diversity distribution and its drivers in rhizosphere soil of Hami melon orchards in different regions of Xinjiang.

BACKGROUND: The unique climatic conditions of the Xinjiang region nurture rich melon and fruit resources, the melon and fruit sugar sources provide sufficient nutrients for the survival of yeast, and the diverse habitats accompanied by extreme climatic conditions promote the production of yeast diversity and strain resources. However, the relationship between yeast species and their relationship with environmental factors in the soil of Xinjiang specialty cash crop Hami melon is not clear. Here, we aimed to characterize the diversity, community structure, and relationship between yeast species and environmental factors in Hami melon orchards soils in different regions of Xinjiang, China. RESULTS: Based on Illumina MiSeq high-throughput sequencing analysis of the D1 domain of the LSU rRNA genes, the community richness of yeast in the soil of Northern Xinjiang was higher than in the Southern and Eastern Xinjiang, but the community diversity was significantly lower in the Northern Xinjiang than in the Southern and Eastern Xinjiang. A total of 86 OTUs were classified into 59 genera and 86 species. Most OTUs (90.4%) belonged to the Basidiomycota; only a few (9.6%) belonged to Ascomycota. The most dominant species in the Southern, Eastern and Northern Xinjiang were Filobasidium magnum (17.90%), Solicoccozyma aeria (35.83%) and Filobasidium magnum (75.36%), respectively. Principal coordinates analysis (PCoA) showed that the yeast community composition in the soils of the three regions were obviously different, with the Southern and Eastern Xinjiang having more similar yeast community. Redundancy analysis (RDA) showed that soil factors such as conductivity (CO), total phosphorus (TP) and Total potassium (TK) and climate factors such as average annual precipitation (PRCP), relative humidity (RH) and net solar radiation intensity (SWGNT) were significantly correlated with yeast communities (P < 0.05). CONCLUSION: There are abundant yeast resources in the rhizosphere soil of Hami melon orchard in Xinjiang, and there are obvious differences in the diversity and community structure of yeast in the three regions of Xinjiang. Differences in climatic factors related to precipitation, humidity and solar radiation intensity and soil factors related to conductivity, total phosphorus and total potassium are key factors driving yeast diversity and community structure.

Effect of hydroxychloroquine on preeclampsia in lupus pregnancies: a propensity score-matched analysis and meta-analysis.

BACKGROUND: Hydroxychloroquine (HCQ) is the primary medication in the treatment of pregnancy with systemic lupus erythematosus (SLE) for its efficacy and safety. However, the effect of HCQ on preeclampsia prevention remains controversial. OBJECTIVE: This study aimed to investigate whether HCQ has an effect on preeclampsia prevention and other pregnancy outcomes among lupus pregnancy. METHODS: We conducted a retrospective cohort study of 119 pregnant women with SLE. After the propensity score matching of baseline characteristics, the population was divided into the HCQ treatment group and HCQ nontreatment group. Then, we compared the preeclampsia and other pregnancy outcomes between HCQ treatment and nontreatment groups. Furthermore, we combined our data and previous studies for a meta-analysis. RESULTS: In our data, HCQ did not increase the risk of premature rupture of membranes, bleeding during pregnancy, preeclampsia, intrauterine distress, gestational age at delivery, preterm birth, and postpartum hemorrhage. There was no significant association between HCQ treatment and preeclampsia prevention. Besides, the meta-analysis showed a similar result that HCQ did not significantly decrease the rate of preeclampsia (RR = 0.61, 95%CI = 0.34-1.11). CONCLUSION: This study found that HCQ treatment was safe, but did not significantly reduce preeclampsia among lupus pregnancies.

Preconception diabetes mellitus and adverse pregnancy outcomes in over 6.4 million women: A population-based cohort study in China.

BACKGROUND: Diabetes mellitus (DM) increases the risk of adverse maternal and neonatal outcomes, and optimization of glycemic control during pregnancy can help mitigate risks associated with diabetes. However, studies seldom focus precisely on maternal blood glucose level prior to pregnancy. We aimed to evaluate the associations between preconception blood fasting plasma glucose (FPG) level and subsequent pregnancy outcomes. METHODS AND FINDINGS: We conducted a population-based retrospective cohort study among 6,447,339 women aged 20-49 years old who participated in National Free Pre-Pregnancy Checkups Project and completed pregnancy outcomes follow-up between 2010 and 2016 in China. During the preconception health examination, serum FPG concentration was measured, and self-reported history of DM was collected. Women were classified into three groups (normal FPG group: FPG < 5.6 mmol/L and no self-reported history of DM; impaired fasting glucose [IFG]: FPG 5.6-6.9 mmol/L and no self-reported history of DM; and DM: FPG ≥ 7.0 mmol/L or self-reported history of DM). The primary outcomes were adverse pregnancy outcomes, including spontaneous abortion, preterm birth (PTB), macrosomia, small for gestational age infant (SGA), birth defect, and perinatal infant death. Logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval (CI) after adjusting for confounding variables. The mean age of women was 25.24 years, 91.47% were of Han nationality, and 92.85% were from rural areas. The incidence of DM and IFG was 1.18% (76,297) and 13.15% (847,737), respectively. Only 917 (1.20%) women reported a history of DM (awareness of their DM status), of whom 37.28% (337) had an elevated preconception FPG level (≥ 5.6 mmol/L), regarded as noncontrolled DM. A total of 1,005,568 (15.60%) women had adverse pregnancy outcomes. Compared with women with normal FPG, women with IFG had higher risks of spontaneous abortion (OR 1.08; 95% CI 1.06-1.09; P < 0.001), PTB (1.02; 1.01-1.03; P < 0.001), macrosomia (1.07; 1.06-1.08; P < 0.001), SGA (1.06; 1.02-1.10; P = 0.007), and perinatal infant death (1.08; 1.03-1.12; P < 0.001); the corresponding ORs for women with DM were 1.11 (95% CI 1.07-1.15; P < 0.001), 1.17 (1.14-1.20; P < 0.001), 1.13 (1.09-1.16; P < 0.001), 1.17 (1.04-1.32; P = 0.008), and 1.59 (1.44-1.76; P < 0.001). Women with DM also had a higher risk of birth defect (OR 1.42; 95% CI 1.15-1.91; P = 0.002). Among women without self-reported history of DM, there was a positive linear association between FPG levels and spontaneous abortion, PTB, macrosomia, SGA, and perinatal infant death (P for trend <0.001, <0.001, <0.001, 0.001, <0.001). Information about hypoglycemic medication before or during pregnancy was not collected, and we cannot adjust it in the analysis, which could result in underestimation of risks. Data on 2-hour plasma glucose level and HbA1c concentration were not available, and the glycemic control status was evaluated according to FPG value in women with DM. CONCLUSIONS: Women with preconception IFG or DM had higher risk of adverse pregnancy outcomes, including spontaneous abortion, PTB, macrosomia, SGA, and perinatal infant death. Preconception glycemic control through appropriate methods is one of the most important aspects of preconception care and should not be ignored by policy makers.

Prevalence, risk factors and associated adverse pregnancy outcomes of anaemia in Chinese pregnant women: a multicentre retrospective study.

BACKGROUND: Anaemia in pregnant women is a public health problem, especially in developing countries. The aim of this study was to assess the prevalence and related risk factors of anaemia during pregnancy in a large multicentre retrospective study (n = 44,002) and to determine the adverse pregnancy outcomes in women with or without anaemia. METHODS: The study is a secondary data analysis of a retrospective study named "Gestational diabetes mellitus Prevalence Survey (GPS) study in China". Structured questionnaires were used to collect socio-demographic characteristics, haemoglobin levels and pregnancy outcomes from all the participants. Anaemia in pregnancy is defined as haemoglobin < 110 g/L. We used SPSS software to assess the predictors of anaemia and associated adverse pregnancy outcomes. RESULTS: The overall prevalence of anaemia was 23.5%. Maternal anaemia was significantly associated with maternal age ≥ 35 years (AOR = 1.386), family per capita monthly income< 1000 CNY (AOR = 1.671), rural residence (AOR = 1.308) and pre-pregnancy BMI < 18.5 kg/m2 (AOR = 1.237). Adverse pregnancy outcomes, including GDM, polyhydramnios, preterm birth, low birth weight (< 2500 g), neonatal complications and NICU admission, increased significantly (P < 0.001) in those with anaemia than those without. CONCLUSIONS: The results indicated that anaemia continues to be a severe health problem among pregnant women in China. Anaemia is associated with adverse pregnancy outcomes. Pregnant women should receive routine antenatal care and be given selective iron supplementation when appropriate.

Hemoglobin levels during the first trimester of pregnancy are associated with the risk of gestational diabetes mellitus, pre-eclampsia and preterm birth in Chinese women: a retrospective study.

BACKGROUND: Hemoglobin (Hb) measurement is a standard test among pregnant women during the first perinatal visit that is used to evaluate physical status and anemia. However, studies focusing on Hb levels and pregnancy outcomes are scarce. This study aimed to determine whether Hb levels in early pregnancy were associated with the risk of gestational diabetes mellitus (GDM), pre-eclampsia (PE) and preterm birth. METHODS: A hospital-based retrospective study was conducted among 21,577 singleton, non-smoking pregnancies between June 2013 and January 2015. The demographic data and medical information of each participant were collected individually through questionnaires and patient medical records. Odds ratios were generated using a multivariate logistic regression analysis to evaluate the relative risk of GDM, PE and preterm birth continuously and across different hemoglobin ranges in the overall population and in women from different pre-pregnancy body mass index (BMI) categories, respectively. The level of statistical significance was set at 0.05. RESULTS: (1) For women who were underweight, normal-weight, overweight and obese, early pregnancy Hb levels were 127.8 ± 10.1 g/L, 129.6 ± 9.7 g/L, 132.2 ± 9.5 g/L and 133.4 ± 9.4 g/L, respectively. (2) Women with GDM and PE had significantly increased Hb levels during early pregnancy compared with controls, whereas women with preterm birth processed significantly decreased Hb levels. (3) After adjusting for confounders, the risks for GDM and PE increased with high maternal Hb (OR: 1.27 for Hb 130-149; OR: 2.06 for Hb ≥ 150 g/L), and the risk for preterm birth decreased with high maternal Hb (OR: 1.30 for Hb 130-149; OR: 2.38 for Hb ≥ 150 g/L) and increased with low maternal Hb (OR: 1.41 for Hb <  110 g/L). Among women whose BMI was < 24 kg/m2, high GDM (OR: 1.27 for Hb 130-149; OR: 1.84 for Hb ≥ 150 g/L) and low preterm rates (OR: 0.77 for Hb 130-149; OR: 0.23 for Hb ≥ 150 g/L) were observed with high Hb, whereas in women whose BMI was ≥24 kg/m2, only high GDM rates were observed with Hb > 150 g/L (OR: 2.33). CONCLUSION: These findings suggest that Hb levels during early pregnancy play a role in predicting the risk of GDM, PE and preterm birth.

Recommended reference values for serum lipids during early and middle pregnancy: a retrospective study from China.

BACKGROUND: Disturbances in maternal lipid metabolism have been shown to increase the risk of adverse pregnancy outcomes. However, there is no consensus as to what constitutes normal maternal lipid values during pregnancy. Thus, the aim of this study was to establish serum lipid reference ranges during early and middle pregnancy. METHODS: We conducted a retrospective survey in Beijing from 2013 to 2014. A total of 17,610 singleton pregnancies with lipid data from early and middle pregnancy were included. First, after excluding women with adverse pregnancy outcomes, we performed a descriptive analysis of total cholesterol (TC), triglycerides (TG), high-density lipid cholesterol (HDL-C) and low-density lipid cholesterol (LDL-C) levels using means and standard deviations to determine appropriate percentiles. Second, in the total population, we examined the lipid levels in different trimesters with the risk of adverse pregnancy outcomes using categorical analyses and logistic regression models. Third, we determined the lipid reference range in early and middle pregnancy based on the first two results. Finally, based on the reference ranges we determined, we assessed whether the number of abnormal lipid values affected the risk of adverse pregnancy outcomes. RESULTS: (1) Serum levels of TC, TG, LDL-C and HDL-C all increased significantly from early to middle pregnancy, with the greatest increase in TG. (2) A trend towards an increasing incidence of adverse pregnancy outcomes was observed with increasing levels of TC, TG, and LDL-C and decreasing levels of HDL-C in both early and middle pregnancy. (3) We recommend that serum TC, TG and LDL-C reference values in early and middle pregnancy should be less than the 95th percentiles, whereas that of HDL-C should be greater than the 5th percentile, i.e., in early pregnancy, TC < 5.64 mmol/L, TG < 1.95 mmol/L, HDL-C > 1.23 mmol/L, and LDL-C < 3.27 mmol/L, and in middle pregnancy, TC < 7.50 mmol/L, TG < 3.56 mmol/L, HDL-C > 1.41 mmol/L, and LDL-C < 4.83 mmol/L. (4) Higher numbers out-of-range lipids during early and middle pregnancy were correlated with a higher risk of adverse pregnancy outcomes. CONCLUSIONS: The reference ranges recommended in this paper can identify pregnant women with unfavourable lipid values.

A randomized clinical trial of exercise during pregnancy to prevent gestational diabetes mellitus and improve pregnancy outcome in overweight and obese pregnant women.

BACKGROUND: Obesity and being overweight are becoming epidemic, and indeed, the proportion of such women of reproductive age has increased in recent times. Being overweight or obese prior to pregnancy is a risk factor for gestational diabetes mellitus, and increases the risk of adverse pregnancy outcome for both mothers and their offspring. Furthermore, the combination of gestational diabetes mellitus with obesity/overweight status may increase the risk of adverse pregnancy outcome attributable to either factor alone. Regular exercise has the potential to reduce the risk of developing gestational diabetes mellitus and can be used during pregnancy; however, its efficacy remain controversial. At present, most exercise training interventions are implemented on Caucasian women and in the second trimester, and there is a paucity of studies focusing on overweight/obese pregnant women. OBJECTIVE: We sought to test the efficacy of regular exercise in early pregnancy to prevent gestational diabetes mellitus in Chinese overweight/obese pregnant women. STUDY DESIGN: This was a prospective randomized clinical trial in which nonsmoking women age >18 years with a singleton pregnancy who met the criteria for overweight/obese status (body mass index 24≤28 kg/m2) and had an uncomplicated pregnancy at <12+6 weeks of gestation were randomly allocated to either exercise or a control group. Patients did not have contraindications to physical activity. Patients allocated to the exercise group were assigned to exercise 3 times per week (at least 30 min/session with a rating of perceived exertion between 12-14) via a cycling program begun within 3 days of randomization until 37 weeks of gestation. Those in the control group continued their usual daily activities. Both groups received standard prenatal care, albeit without special dietary recommendations. The primary outcome was incidence of gestational diabetes mellitus. RESULTS: From December 2014 through July 2016, 300 singleton women at 10 weeks' gestational age and with a mean prepregnancy body mass index of 26.78 ± 2.75 kg/m2 were recruited. They were randomized into an exercise group (n = 150) or a control group (n = 150). In all, 39 (26.0%) and 38 (25.3%) participants were obese in each group, respectively. Women randomized to the exercise group had a significantly lower incidence of gestational diabetes mellitus (22.0% vs 40.6%; P < .001). These women also had significantly less gestational weight gain by 25 gestational weeks (4.08 ± 3.02 vs 5.92 ± 2.58 kg; P < .001) and at the end of pregnancy (8.38 ± 3.65 vs 10.47 ± 3.33 kg; P < .001), and reduced insulin resistance levels (2.92 ± 1.27 vs 3.38 ± 2.00; P = .033) at 25 gestational weeks. Other secondary outcomes, including gestational weight gain between 25-36 gestational weeks (4.55 ± 2.06 vs 4.59 ± 2.31 kg; P = .9), insulin resistance levels at 36 gestational weeks (3.56 ± 1.89 vs 4.07 ± 2.33; P = .1), hypertensive disorders of pregnancy (17.0% vs 19.3%; odds ratio, 0.854; 95% confidence interval, 0.434-2.683; P = .6), cesarean delivery (except for scar uterus) (29.5% vs 32.5%; odds ratio, 0.869; 95% confidence interval, 0.494-1.529; P = .6), mean gestational age at birth (39.02 ± 1.29 vs 38.89 ± 1.37 weeks' gestation; P = .5); preterm birth (2.7% vs 4.4%, odds ratio, 0.600; 95% confidence interval, 0.140-2.573; P = .5), macrosomia (defined as birthweight >4000 g) (6.3% vs 9.6%; odds ratio, 0.624; 95% confidence interval, 0.233-1.673; P = .3), and large-for-gestational-age infants (14.3% vs 22.8%; odds ratio, 0.564; 95% confidence interval, 0.284-1.121; P = .1) were also lower in the exercise group compared to the control group, but without significant difference. However, infants born to women following the exercise intervention had a significantly lower birthweight compared with those born to women allocated to the control group (3345.27 ± 397.07 vs 3457.46 ± 446.00 g; P = .049). CONCLUSION: Cycling exercise initiated early in pregnancy and performed at least 30 minutes, 3 times per week, is associated with a significant reduction in the frequency of gestational diabetes mellitus in overweight/obese pregnant women. And this effect is very relevant to that exercise at the beginning of pregnancy decreases the gestational weight gain before the mid-second trimester. Furthermore, there was no evidence that the exercise prescribed in this study increased the risk of preterm birth or reduced the mean gestational age at birth.

Expression of chemokine receptor CXCR4 is closely correlated with clinical outcome in human nasopharyngeal carcinoma.

The CXC chemokine receptor 4 (CXCR4) has been reported to be involved in the development and progression of nasopharyngeal carcinoma (NPC). However, the role of CXCR4 in clinical outcome and prognosis of NPC patients remains controversial. In the present study, we investigated and reviewed the expression of CXCR4 in NPC tissues and then analyzed the definitive role of CXCR4 in clinical outcome and prognosis. Here, we found that the expression level of CXCR4 was significantly higher in NPC cancer specimens (61/98) than that in paired non-tumor tissues (p < 0.001). Together with our pathological analysis, statistic analysis revealed that CXCR4 expression was indeed closely correlated with UICC stage (p = 0.000), N stage (p = 0.019), and metastasis (p = 0.000). Most importantly, the systematic review combined with our survival and multivariate analysis that revealed high expression of CXCR4 was obviously associated with poor overall survival (OS) (p = 0.000) and progression-free survival (PFS) (p = 0.000) and can act as an independent prognostic factor in NPC patients. In conclusion, this study suggests that CXCR4 is highly activated and expressed in the development of NPC and may be recommended as an indicator in the diagnosis of NPC. Thus, targeting of CXCR4 gene or protein could be used as a potential therapy for NPC.

Exercise intervention during pregnancy can be used to manage weight gain and improve pregnancy outcomes in women with gestational diabetes mellitus.

BACKGROUND: The study aimed to evaluate whether exercise intervention can be applied to pregnant women with gestational diabetes mellitus (GDM) for controlling gestational weight gain (GWG) and combating GDM-related outcomes. METHODS: Retrospective six months analysis of 14,168 single pregnant women without diabetes from 15 hospitals in Beijing in 2013. Each participant's demographic data, interventions condition and medical information were collected individually by questionnaires and relying on medical records. The level of statistical significance was set equal to 0.05. RESULTS: 2750 (19.4%) pregnant women were diagnosed with GDM, 74.9% of them received exercise intervention during pregnancy, and the starting time was 25.8 ± 3.7 gestational weeks. Women with GDM with exercise intervention (GDM-E) had the lowest BMI increase during late and mid-pregnancy than women with GDM without exercise intervention (GDM-nE) (2.05 ± 1.32 kg/m(2) vs. 2.40 ± 1.30 kg/m(2), p < 0.01) and non-GDM women (2.05 ± 1.32 kg/m(2) vs. 2.77 ± 1.21 kg/m(2), p < 0.01). Moreover, GDM-E group experienced a significantly lower risk of preterm birth (5.58% vs. 7.98%, p < 0.001), low birth weight (1.03% vs. 2.06 %, p < 0.001) and macrosomia (9.51 % vs. 11.18%, p > 0.05) than GDM-nE group. After including dietary factors in the analysis, women with GDM without either dietary or exercise intervention (GDM-nDnE) had the highest risk of preterm birth(OR = 1.64, 95 % CI, 1.14-2.36), while women with GDM with dietary intervention only (GDM-DnE) had the highest risk of low birth weight (OR = 3.10, 95 % CI, 1.23-7.81). However, women with GDM with both dietary and exercise intervention had the lowest rate of macrosomia. CONCLUSION: Exercise intervention is a suitable non-invasive therapeutic option that can be readily applied to manage weight gain and improve pregnancy outcomes in women with GDM.

[Variation of prevalence of macrosomia and cesarean section and its influencing factors].

OBJECTIVE: To investigate the varaiation of the incidence of macrosomia and its influencing factors. METHODS: A population-based study of 25 944 pregnant women, who delivered in Peking University First Hospital in term birth, with singleton, between Jan. 1, 2006 and Dec. 31, 2013 and accepted the gestational diabetes mellitus (GDM) screening and diagnosis, was performed. The women are grouped according to the different clinical interventions at different period. Women delivered between Jan.1, 2006 and Dec. 31, 2006 was defined as Group 2006, and they were diagnosed with glucose metabolism disorder [gestational impaired glucose tolerance (GIGT) and GDM] and intervened only when meeting National diabetes data group (NDDG) criteria. Women delivered between Jan. 1, 2007 and Apr. 30, 2011 were defined as Group post 2007, and NDDG criteria was also applied in this period. Women delivered between May. 1, 2011 and Dec. 31, 2013 were defined as Group post 2011, and Ministry of Health (MOH) of China was used for GDM diagnosis in this group. All pregnant women in Group post 2007 accepted the preliminary pregnancy nutrition advice and weight management. All participants met MOH criteria were diagnosed as glucose metabolism disorder in this study, in which women diagnosed and intervened in pregnancy were defined as Group diagnosis and those not being identified during pregnancy were defined as Group missed diagnosis. It was analyzed retrospectively for the incidence of macrosomia and the influencing factor. RESULTS: (1) The prevalence of macrosomia and cesarean section was decreased every year from Jan. 2006 to Dec. 2013. The incidence of macrosomia was 9.14% in 2006, reduced to 8.02% in 2007-2011 and 6.79% in 2011-2013. The incidence of cesarean section was 55.22%, reduced to 51.04% in 2007-2011 and 44.15% in 2011-2013. However, there was not remarkable change in the prevalence of small for gestational age (P > 0.05). (2) Compared with Group 2006, the incidence of cesarean section was lower in Group post 2007 [51.04% (6 504/12 744) vs 55.22% (1 371/2 483)], and the difference is significantly (P < 0.05). Meanwhile, the incidence of cesarean section (44.15%, 4 732/10 717) and macrosomia (6.79%,728/10 717) in Group post 2011 was lower significantly than Group 2006 and Group post 2007 (P < 0.05). (3) The incidence of macrosomia was 7.41% (1 129/15 227) and 6.61% (1 006/15 227) respectively in Group diagnosis and Group missed diagnosis before May 2011, combined 14.02% (2 135/15 227) in total. It was increased significantly in the incidence of GDM 21.41% (2 294/10 717) after May 2011 compared with that before (P < 0.05). The incidence of macrosomia was decreased significantly using MOH criteria in GDM women since 2011. It was the downtrend in the incidence of macrosomia since 2007 in non GDM women. However, there was no difference in SGA in different period. (4) In glucose metabolism disorder women, compared with Group 2006 and Group post 2007, the incidence of macrosomia and cesarean section was lower in Group post 2011, and the difference is significantly (P < 0.05). However, there was no significant difference in the incidence of macrosomia and cesarean section between Group 2006 and Group post 2007, and there was no difference in SGA in the 3 groups ( P > 0.05). In non GDM women, the incidence of macrosomia and cesarean section was lower in Group post 2011 than Group 2006 (P < 0.05); meanwhile, it was the downtrend in the incidence of macrosomia in Group post 2007 compared to Group 2006, and the difference of the incidence of cesarean section was significant (P < 0.05). CONCLUSION: The prevalence of macrosomia and cesarean section might be reduced by application of suitable criteria for diagnosis of GDM and education on nutrition during pregnancy.

[Characteristics of oral glucose tolerance test in 9803 pregnant women of different pre-pregnancy body mass index and its relationship with the incidence of gestational diabetes mellitus].

OBJECTIVE: To investigate the values and characteristics of 75 g oral glucose tolerance test (OGTT) in women with different pre-pregnancy body mass index (BMI) and to evaluate the risk of gestational diabetes mellitus (GDM). METHODS: Medical records of 9803 pregnant women attending the Peking University First Hospital and delivered between July 1, 2011 and December 31, 2013 were retrospectively analyzed. The frequency of adverse pregnancy outcomes across different degrees pre-pregnancy BMI was calculated. We divided participants into 4 groups based on pre-pregnancy BMI, underweight: BMI<18.5 kg/m(2) (1221 cases), normal weight: 18.5-23.9 kg/m(2) (6594 cases), overweight: 24-27.9 kg/m(2) (1549 cases), obesity: ≥28.0 kg/m(2) (439 cases). The diagnosis of GDM was made when any one of the values was met or exceeded in 75 g OGTT. The characteristics of 75 g OGTT and the incidence of GDM were analyzed. RESULTS: (1) The average age, pre-pregnancy weight, height and pre-pregnancy BMI of the participants was (30.5±3.7) years, (57.7±9.0) kg, (162.8±4.9) cm and (21.8±3.2) kg/m(2), respectively. All the values of 75 g OGTT were presented normal distribution. (2) There was statistical difference in the glucose levels among women with different pre-pregnancy BMI. The fasting, 1-hour, 2-hour glucose were (4.55±0.34), (7.31±1.54), (6.38±1.23) mmol/L in underweight women, (4.65±0.38), (7.70±1.59), (6.70±1.27) mmol/L in normal weight women, (4.82±0.47), (8.29±1.67), (7.04±1.29) mmol/L in overweight women and (4.94±0.48), (8.56±1.64), (7.10±1.35) mmol/L in obesity women (P<0.01). (3) The incidence of GDM was 21.76% (2133/9803) in our study. There were 1374 cases (64.42%, 1374/2133) with only one abnormal OGTT value while 759 cases (35.58%, 759/2133) with two or more abnormal values. The incidence of GDM in women with underweight, normal weight, overweight and obesity was 12.53% (153/1221), 19.71% (1300/6594), 32.73% (507/1549) and 39.41% (173/439), respectively (P<0.05). Meanwhile, the incidence of women with two and more abnormal OGTT value in GDM was increased as the pre-pregnancy increasing. CONCLUSION: The risk of GDM is increased as pre-pregnancy BMI increasing, and the risk of GDM increases significantly in women with pre-pregnancy overweight or obesity.

Rapid and sensitive detection of human astrovirus in water samples by loop-mediated isothermal amplification with hydroxynaphthol blue dye.

BACKGROUND: The aim of this paper was to develop a reverse transcription loop-mediated isothermal amplification (RT-LAMP) method for rapid, sensitive and inexpensive detection of astrovirus. RESULTS: The detection limit of LAMP using in vitro RNA transcripts was 3.6 × 10 copies·µL⁻¹, which is as sensitive as the presently used PCR assays. However, the LAMP products could be identified as different colors with the naked eye following staining with hydroxynaphthol blue dye (HNB). No cross-reactivity with other gastroenteric viruses (rotavirus and norovirus) was observed, indicating the relatively high specificity of LAMP. The RT-LAMP method with HNB was used to effectively detect astrovirus in reclaimed water samples. CONCLUSIONS: The LAMP technique described in this study is a cheap, sensitive, specific and rapid method for the detection of astrovirus. The RT-LAMP method can be simply applied for the specific detection of astrovirus and has the potential to be utilized in the field as a screening test.

Modeling and analysis of a human papilloma virus transmission model with impact of media.

The human papillomavirus (HPV) is threatening human health as it spreads globally in varying degrees. On the other hand, the speed and scope of information transmission continues to increase, as well as the significant increase in the number of HPV-related news reports, it has never been more important to explore the role of media news coverage in the spread and control of the virus. Using a decreasing factor that captures the impact of media on the actions of people, this paper develops a model that characterizes the dynamics of HPV transmission with media impact, vaccination and recovery. We obtain global stability of equilibrium points employing geometric method, and further yield effective methods to contain the HPV pandemic by sensitivity analysis. With the center manifold theory, we show that there is a forward bifurcation when R0=1. Our study suggested that, besides controlling contact between infected and susceptible populations and improving effective vaccine coverage, a better intervention would be to strengthen media coverage. In addition, we demonstrated that contact rate and the effect of media coverage result in multiple epidemics of infection when certain conditions are met, implying that interventions need to be tailored to specific situations.

Population Pharmacodynamic Models of Risperidone on PANSS Total Scores and Prolactin Levels in Schizophrenia.

Currently, research predominantly focuses on evaluating clinical effects at specific time points while neglecting underlying patterns within the treatment process. This study aims to analyze the dynamic alterations in PANSS total scores and prolactin levels in patients with schizophrenia treated with risperidone, along with the influencing covariates. Using data from an 8-week randomized, double-blind, multicenter clinical trial, a population pharmacodynamic model was established for the PANSS total scores of and prolactin levels in patients treated with risperidone. The base model employed was the Emax model. Covariate selection was conducted using a stepwise forward inclusion and backward elimination approach. A total of 144 patients were included in this analysis, with 807 PANSS total scores and 531 prolactin concentration values. The PANSS total scores of the patients treated with risperidone decreased over time, fitting a proportionally parameterized sigmoid Emax model with covariates including baseline score, course of the disease, gender, plasma calcium ions, and lactate dehydrogenase levels. The increase in prolactin levels conformed to the ordinary Emax model, with covariates encompassing course of the disease, gender, weight, red blood cell count, and triglyceride levels. The impacts of the baseline scores and the course of the disease on the reduction of the PANSS scores, as well as the influence of gender on the elevation of prolactin levels, each exceeded 20%. This study provides valuable quantitative data regarding PANSS total scores and prolactin levels among patients undergoing risperidone treatment across various physiological conditions.

Significant associations between GSTM1/GSTT1 polymorphisms and nasopharyngeal cancer risk.

Glutathione S-transferases play a critical role in the detoxification and elimination of electrophilic carcinogens by conjugating them to glutathione. Homozygous deletions of GSTM1 and GSTT1 have been suggested as risk factors for some cancers, including colorectal, pancreatic, and esophageal cancers. Results of previous individual studies published to estimate the associations between GSTM1/GSTT1 polymorphisms and nasopharyngeal cancer (NPC) risk remained controversial. Thus, we carried out a meta-analysis by pooling the odds ratios (ORs) with corresponding 95 % confidence intervals (95 % CIs) of all currently available case-control studies to shed some light on the contradictory finding. A comprehensive search of the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases up to October 20, 2012 was performed to identify eligible studies. A total of 15 separate publications involving 2,226 NPC cases and 3,339 controls were finally included into this meta-analysis. The meta-analysis of total studies showed that the null genotypes of GSTM1 and GSTT1 were both significantly associated with increased risk of NPC (for GSTM1: OR = 1.54, 95 % CI 1.28-1.86, P OR < 0.001; for GSTT1: OR = 2.25, 95 % CI 1.50-3.36, P OR < 0.001). Subgroup analysis by ethnicity suggested that carriers of both GSTM1 and GSTT1 null genotypes in Asians were more susceptible to NPC. Additionally, in the subgroup analysis based on the sample size, significant associations of the GSTM1 and GSTT1 polymorphisms with NPC susceptibility were identified among studies both with larger case sample size (number of cases ≥ 100) and smaller case sample size (number of cases <100). Sensitivity analysis confirmed the stability of our results. These results indicate that the GSTM1 and GSTT1 polymorphisms may play crucial roles in the development of NPC, especially in Asians.

[Analysis of the effects of gestational diabetes mellitus based on abnormal blood glucose on pregnancy outcomes].

OBJECTIVE: To investigate the relationship of different types of gestational diabetes mellitus (GDM) and pregnancy outcomes. METHODS: A total of 4090 cases, who received prenatal examination and delivered in Peking University First Hospital and performed a 75 g oral glucose tolerance test (75 g OGTT) at 24-28 gestational weeks, from January. 1(st), 2011 to Jul 31(st), 2012 , were divided into 2 groups. Normal blood glucose group:the result of OGTT (fasting plasma glucose, 1 hour glucose and 2 hour glucose ) was normal; Gestational diabetes mellitus group (GDM group): the result of OGTT was abnormal at any time point. GDM group were separated into A, B and C. GDM A means fasting plasma glucose annormal but others were normal, GDM B:fasting plasma glucose, 1 hour and/or 2 hour glucose abnormal, GDM C:fasting plasma glucose normal. To analyse the effect of different number of abnormal result of OGTT on pregnancy outcomes, GDM group were divided into I, II and III.GDMI means one abnormal blood glucose of OGTT result, GDM II: two abnormal blood glucose and GDM III:three abnormal blood glucose. We analyzed the pregnant outcomes of each group. RESULTS: (1) Among the 4090 cases, 858 cases (21.98%) were diagnosed as GDM (GDM group), and 82 cases (9.6%, 82/858) were treated with insulin.other 3232 cases with normal blood glucose (normal blood glucose group). In GDM group, the rate of cesarean section (51.9%, 445/858), premature delivery (8.4%, 72/858) and LGA (5.9%, 51/858) were respectively significantly higher than those of normal blood glucose group [ (43.5%, 1406/3232), (5.8%, 189/3232) and(4.2%, 137/3232)] (P < 0.05). But, there was no statistically significant differences for the rate of macrosomia (P > 0.05) between the GDM group(6.8%, 58/858) and normal blood glucose group (6.2%, 199/3232) . (2) In the GDM group, GDM A was 317 cases (36.9%), GDM B 239 cases (27.8%), GDM C 302 cases (35.2%). The incidence of Macrosomia and LGA in GDM B was significantly higher than that in GDM C and normal blood glucose group (P < 0.05). Comparing with GDM A , there was no statistically significance in GDM B and GDM C (P > 0.05). (3) In GDM group, GDMIwas 521 cases (60.7%), GDM II203 cases (15.6%), GDM III 134 cases (23.7%). Compared with the normal blood glucose group, GDM III had a significantly higher incidence of macrosomia and LGA and cesarean section(P < 0.01);and GDM IIhad only a significantly higher incidence of cesarean section(P < 0.01). (4) Among the 4090 cases, there were 1118 patients (27.3%) whose fasting blood glucose was below 4.4 mmol/L, of which 55 cases were diagnosed as GDM. There were 4 premature infants and 1 macrosomia. CONCLUSIONS: The GDM group with more than FBG ≥ 5.1 mmol/L had a higher incidence of adverse pregnancy outcomes, it suggested that we should pay more attention and take actively intervented; the pregnant woman is not recommended for 75g OGTT detection when fasting blood glucose was below 4.4 mmol/L because of the low rate of GDM and adverse pregnancy outcomes among them.

Stability and Hopf bifurcation of an SIR epidemic model with density-dependent transmission and Allee effect.

In this paper, an SIR model with a strong Allee effect and density-dependent transmission is proposed, and its characteristic dynamics are investigated. The elementary mathematical characteristic of the model is studied, including positivity, boundedness and the existence of equilibrium. The local asymptotic stability of the equilibrium points is analyzed using linear stability analysis. Our results indicate that the asymptotic dynamics of the model are not only determined using the basic reproduction number ${R_0}$. If ${R_0} < 1$, there are three disease-free equilibrium points, and a disease-free equilibrium is always stable. At the same time, the conditions for other disease-free equilibrium points to be bistable were determined. If ${R_0} > 1$ and in certain conditions, either an endemic equilibrium emerges and is locally asymptotically stable, or the endemic equilibrium becomes unstable. What must be emphasized is that there is a locally asymptotically stable limit cycle when the latter happens. The Hopf bifurcation of the model is also discussed using topological normal forms. The stable limit cycle can be interpreted in a biological significance as a recurrence of the disease. Numerical simulations are used to verify the theoretical analysis. Taking into account both density-dependent transmission of infectious diseases and the Allee effect, the dynamic behavior becomes more interesting than when considering only one of them in the model. The Allee effect makes the SIR epidemic model bistable, which also makes the disappearance of diseases possible, since the disease-free equilibrium in the model is locally asymptotically stable. At the same time, persistent oscillations due to the synergistic effect of density-dependent transmission and the Allee effect may explain the recurrence and disappearance of disease.

Hydroxychloroquine significantly decreases the risk of preeclampsia in pregnant women with autoimmune disorders: a systematic review and meta-analysis.

This meta-analysis aimed to investigate whether hydroxychloroquine (HCQ) intervention could decrease the incidence of preeclampsia and other maternal and fetal outcomes among pregnant women with autoimmune disorders. PubMed, EMBASE, Web of Science, and the Cochrane databases were searched from inception until January 2022. Data on maternal or fetal outcomes of the control and hydroxychloroquine treatment groups were gathered and analyzed. Pooled odds ratio (OR) with 95% confidence intervals (CIs) were determined. Cochran's Q test, I2 statistics, leave-one-out analysis, Baujat plot analysis, GOSH plot analysis, and multivariable meta-regression were applied to assess between-study heterogeneity. The meta-analysis was performed using the Stata V.16.1 software. Baujat plot analysis and GOSH plot analysis were performed using the R V.4.0.0 software. Our study included 21 cohort studies and one case-control study with a total of 3948 pregnancies with immune disorders. HCQ treatment significantly reduced the incidence of preeclampsia (OR 0.45, 95% CI 0.33-0.63, p = 0.000, I2 3.68%). After outlier omission, HCQ treatment significantly reduced the incidence of premature delivery (OR 0.84, 95% CI 0.73-0.96, p = 0.01, I2 44.81%) in pregnant women with autoimmune disorders. In sub-group analysis, HCQ also significantly reduced the incidence of gestational hypertension (OR 0.42, 95% CI 0.26-0.68, p = 0.001, I2 49.33%) and preterm birth (OR 0.63, 95% CI 0.48-0.82, p = 0.001, I2 27.63%) in pregnant women with lupus. The heterogeneity of the findings mentioned above was low to moderate. There were no significant differences in the risk of other outcomes, including gestational diabetes, HELLP syndrome, thrombosis, spontaneous abortion, fetal loss, small for gestational age infant (SGA), low birth weight, stillbirth, APGAR score < 7, and congenital malformation. This meta-analysis indicated that HCQ treatment could significantly decrease the incidence of preeclampsia and premature delivery in pregnant women with autoimmune disorders. In addition, HCQ could reduce the risk of gestational hypertension in pregnant lupus patients.

Matched-pair analysis of the impact of low-dose postoperative radiotherapy on prognosis in patients with advanced hypopharyngeal squamous cell carcinoma without positive surgical margins and extracapsular extension.

Background: We conducted a comparative analysis between low and high-dose postoperative radiotherapy in patients with hypopharyngeal squamous cell carcinoma (HPSCC) in stage III or IV without positive surgical margins and extracapsular extension (ECE). Propensity score matching (PSM) was used to eliminate confounding factors and reduce bias. Methods: The matched-pair analysis included 156 patients divided into two groups: the low-dose radiotherapy group (LD-RT 50 Gy, 78 cases) and the high-dose radiotherapy group (HD-RT 60 Gy, 78 cases). Both cohorts were statistically comparable in terms of age, gender, subsite, and TNM classification. Results: The median follow-up time was 49 months (ranging from 5 to 100 months). The overall survival (OS) rate, progression-free survival (PFS) rate, locoregional control rate (87% vs. 85.7%; p = 0.754), distant metastases-free survival (79.2% vs. 76.6%; p = 0.506), and the occurrence of second primary tumors (96.1% vs. 93.5%; p = 0.347) showed no significant differences between the LD-RT group and the HD-RT group. The 3-year OS was 64.9% and 61% in the low-dose and high-dose group, respectively, and 63% in the entire group (p = 0.547). The 3-year PFS was 63.6% and 54.5% (p = 0.250), respectively, and the 3-year PFS of the entire group was 59.1%. Multivariate analyses revealed that pathological T and N classification, and pathological differentiation were associated with 3-year OS, PFS, and LRFS and were independent prognostic factors (p < 0.05). LD-RT was not associated with an increased risk of death and disease progression compared to HD-RT. Conclusion: The results of postoperative low-dose radiotherapy did not show inferiority to those of high-dose radiation for patients with advanced hypopharyngeal cancer without positive surgical margins and ECE in terms of OS, PFS, locoregional control, and metastases-free survival.