Abstract： With the increasing rise in antidepressant consumption, more and more antidepressants and their metabolic products enter into water and soil environments. This will cause toxicity to animals living in these environments, and antidepressants may be transferred to humans via food chain, leading to human health risks. Based on national and international publications pertaining to environmental pollution and toxic effects of antidepressants during the period between 2005 and 2021, this review summarizes the biological accumulation, acute toxicity, reproductive and developmental toxicity, metabolic effects and biological behavior changes of antidepressants, so as to provide insights into the elucidation of the impact of antidepressants on human health risks.

Objective:To study the effectiveness and safety of intra-amniotic ethacridine injection in pregnancy induction at ≥28 gestational weeks due to fetal demise.Methods:This retrospective study recruited 77 singleton pregnant women who were admitted to Peking University First Hospital at ≥28 gestational weeks, from January 1, 2011 to December 31, 2021, because of fetal demise diagnosed by ultrasound. Four groups were classified according to different methods of induction, including ethacridine success group ( n=63), ethacridine failure group ( n=4), mifepristone plus misoprostol group ( n=5), and spontaneous delivery group ( n=5). Those in the ethacridine success group were further divided into scarred and non-scarred uterus group. The differences in general conditions and delivery outcomes among these women were analyzed using t-test, one-way analysis of variance, Chi-square test, and Mann-Whitney U test or Kruskal-Wallis H test. Results:(1) Among the 67 patients induced by ethacridine, the success rate was 94.0% (63/67). (2) Compared the ethacridine success group with the mifepristone plus misoprostol group or spontaneous delivery group, respectively, there was no significant difference in total labor duration, intrapartum hemorrhage volume, weight of the dead fetus, and the incidence of postpartum hemorrhage, perineal laceration, and intrauterine residue (all P>0.05). No serious complications such as placental abruption, disseminated intravascular coagulation, intrauterine infection, uterine rupture, conversion to cesarean section, or puerperal infection occurred in the three groups. (3) The duration between ethacridine injection and labor onset was shorter in the ethacridine success group than in the mifepristone plus misoprostol group [(28.5±12.0) h vs (54.2±17.6) h, t=－4.45, P<0.001]. (4) Among the 63 cases of ethacridine success group, the outcomes after induction were similar between scarred and non-scarred uterus group (all P>0.05). (5) The median duration between ethacridine injection and labor onset in the ethacridine success group was 26.8 h (2.3-66.0 h), which meant 95% of the patients went into labor within 51.7 h and 100% within 66 h after the injection. Conclusion:Intra-amniotic injection of ethacridine is safe and effective in termination for singleton pregnancy due to fetal demise at the third trimester and the duration from drug administration to labor onset was significantly shorter than that of mifepristone plus misoprostol, without increasing the risk of any complications.

Objective To investigate the effects of sevoflurane pretreatment on the inflammatory response in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB) and the mechanism of myocardial protection.Methods Twenty NYHA class Ⅱ or Ⅲ patients of both sexes,aged ＜ 60 yr,undergoing cardiac valve replacement with CPB,were randomly divided into 2 groups (n=10 each): sevoflurane group (group S) and control group (group C).The patients were premedicated with intramuscular morphine 0.1 mg/kg and scopolamine 0.3 mg.Anesthesia was induced with iv injection of midazolam 0.05-0.08 mg/kg,fentanyl 10-15 μg/kg and pipecuronium 0.08-0.10 mg/kg.The patients were tracheal intubated and mechanically ventilated.Anesthesia was maintained with intermittent iv boluses of midazolam0.03-0.06 mg/kg,fentanyl 5-10μg/kg and pipecuronium 0.04-0.08 mg/kg.Sevoflurane was inhaled before aortic clamping and the end-tidal concentration was rapidly adjusted to 1.0％ and maintained at this level for 30 min in group S.Blood samples were taken from the central vein before skin incision,immediately after aortic clamping,immediately after aortic unclamping and at 30 min after aortic unclamping,at 2,6,12 and 24 h (T1-8) after operation for determination of the concentrations of plasma tumor necrosis factor-α (TNF-α),interleukin-6 (IL) and interleukin-8 (IL-8),intercellular adhesion molecule-1 (ICAM-1),cardiac troponin I (cTnI) and activity of creatine kinase MB (CK-MB).The requirement for cardiovascular drugs was recorded after release of aortic cross clamp.Results Compared with group C,the plasma concentrations of TNF-α,IL-6 and IL-8 were significantly decreased at T3-8,the plasma concentrations of ICAM-1 and cTnl were significantly decreased at T4-8,the activity of plasma CK-MB was significantly decreased at T8,and the requirement for cardiovascular drugs was significantly reduced after release of aortic cross clamp in group S (P ＜0.05).Conclusion Sevoflurane pretreatment can inhibit the inflammatory response and provide myocardial protection to some extent in patients undergoing cardiac valve replacement with CPB.

Objective To investigate the effects of sevoflurane pretreatment on the myocardial injury in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).Methods Twenty NYHA class Ⅱ or Ⅲ patients,aged ＜ 60 yr,undergoing cardiac valve replacement with CPB,were randomly divided into 2 groups (n =10 each):sevoflurane group (group S) and control group (group C).The patients were premeditated with intramuscular morphine and scopolamine.Anesthesia was induced with iv injection of midazolam 0.05-0.08 mg/kg,fentanyl 10-15 μg/kg and pipecuronium 0.08-0.10 mg/kg.Anesthesia was maintained with intermittent iv boluses of midazolam,fentanyl and pipecuronium and in addition sevoflurane was inhaled before aortic clamping and the end-tidal concentration was rapidly increased to 1.0％ and maintained at the level for 5 min in group S.Blood samples were taken from the central vein before skin incision (T1),immediately after aortic clamping (T2 ),at 0 and 30 min after aortic unclamping (T3-4),and at 2,6,12 and 24 h after operation (T5-8) for determination of the concentration of serum cardiac troponin Ⅰ (cTnI) and activities of creatine kinase (CK) and creatine kinase isoenzyme-MB (CK-MB).Myocardial specimens were taken from right auricle before aortic clamping and at 10 min after aortic unclamping for electron microscopic examination.Results The concentration of serum cTnI and activities of CK and CK-MB were significantly increased at T4-8 in both groups ( P ＜ 0.05).The serum cTnI concentration at T4-8 and the activities of CK and CK-MB at T8 were significantly lower in group S than in group C ( P ＜0.05).Different degrees of mitochondrial swelling were observed after aortic unclamping in both groups,but the changes were milder in group S than in group C.Conclusion Sevoflurane pretreatment can attenuate the myocardial injury in patients undergoing cardiac valve replacement with CPB.

Objective:To establish a rat model of neurogenic bladder and analyze the changes in kidney morphology and function and the expression of proteins in AngiotensinⅡ(AngⅡ)/transforming growth factor β1 (TGF-β1)/Smads pathway.Methods:Sprague-Dawley rats were randomly divided into experimental group (spinal nerve amputation, n=36) and control group (sham operation, n=12). At 6, 12, and 24 weeks, the bladder compliance was measured by cystometry, the kidney morphology was detected by B-ultrasound, blood urea nitrogen (BUN) and serum creatinine (Scr) in blood samples were examined, the kidney pathological changes were detected by Masson and HE staining, the distribution of AngⅡ/TGF-β1/Smads pathway proteins was analyzed by immunohistochemisty, and the protein expressions in kidney were detected by Western blotting. Results:Urodynamics showed that the basic bladder pressure in experimental group was higher than that in control group. B-ultrasound showed that compared with the control group, the diameter of the renal pelvis of the rats with nerve dissection gradually increased ( P<0.05), and the hydronephrosis was gradually obvious. Compared with the control group, the BUN and Scr in experimental group gradually increased (both P<0.01). Masson and HE staining showed that compared with the control group, the collagen expression and renal tubulointerstitial scores in experimental group were gradually increased (both P<0.01). Immunohistochemisty showed that compared with the control group, in experimental group the expression of angiotensinⅡ receptor type 1 (AT1), TGF-β receptor 1(TGF-βR1), phosphorylated Smad2 gradually increased (all P<0.01), the pathway inhibitor Smad6 gradually decreased ( P<0.01), and the distribution of each protein in kidney was consistent. Western blotting showed a corresponding expression trend with immunohistochemisty. Conclusions:In neurogenic bladder caused by bilateral spinal nerve amputation, due to bladder dysfunction, increased bladder pressure induces hydronephrosis, destruction of the nephron structure, activation of AngⅡ/TGF-β1/Smads pathway, and renal fibrosis. This method is effective and has clinical similarities, laying a foundation for exploring neurogenic bladder treatment.

Diabetes, Gestational ; blood ; diagnosis ; Female ; Glucose Tolerance Test ; Humans ; Pregnancy ; World Health Organization