BACKGROUND: The optimal antidepressant dosages remain controversial. This study aimed to analyze the efficacy of antidepressants and characterize their dose-response relationships in the treatments of major depressive disorders (MDD). METHODS: We searched multiple databases, including the Embase, Cochrane Central Register of Controlled Trials, PubMed, and Web of Science, for the studies that were conducted between January 8, 2016, and April 30, 2023. The studies are double-blinded, randomized controlled trials (RCTs) involving the adults (≥18 years) with MDD. The primary outcomes were efficacy of antidepressant and the dose-response relationships. A frequentist network meta-analysis was conducted, treating participants with various dosages of the same antidepressant as a single therapy. We also implemented the model-based meta-analysis (MBMA) using a Bayesian method to explore the dose-response relationships. RESULTS: The network meta-analysis comprised 135,180 participants from 602 studies. All the antidepressants were more effective than the placebo; toludesvenlafaxine had the highest odds ratio (OR) of 4.52 (95% confidence interval [CI]: 2.65-7.72), and reboxetine had the lowest OR of 1.34 (95%CI: 1.14-1.57). Moreover, amitriptyline, clomipramine, and reboxetine showed a linear increase in effect size from low to high doses. The effect size of toludesvenlafaxine increased significantly up to 80 mg/day and subsequently maintained the maximal dose up to 160 mg/day while the predictive curves of nefazodone were fairly flat in different dosages. CONCLUSIONS: Although most antidepressants were more efficacious than placebo in treating MDD, no consistent dose-response relationship between any antidepressants was observed. For most antidepressants, the maximum efficacy was achieved at lower or middle prescribed doses, rather than at the upper limit. REGISTRATION No. CRD42023427480; https://www.crd.york.ac.uk/prospero/display_record.php?
Humans ; Antidepressive Agents/therapeutic use* ; Depressive Disorder, Major/drug therapy* ; Dose-Response Relationship, Drug ; Randomized Controlled Trials as Topic

Objective To explore the changes in inflammatory reactions in tail-suspension mice infected by Klebsiella pneumoniae from spaceflight.Methods Tail suspension was used to simulate the physiological effects of microgravity.C57BL/6 mice were randomly divided into control (Con),control+K.pneumoniae T16-169 (Con+T16-169),tail suspension (TS) and tail suspension+K.pneumoniae T16-169 (TS+T16-169) groups.The level of inflammatory cytokines TNF-α,IL-6 and IL-1β mRNA in lung tissue and the plasma cytokine concentration were detected by RT-qPCR and xMAP technology,and HE staining was used to represent the morphological changes in lung tissue.Results Compared with the control group,the expression of inflammatory cytokines in lung tissue and plasma concentrations of all experimental groups were increased,and the difference in TS+T16-169 group was the most significant (P<0.01 or P<0.001).HE staining showed that the lung tissues in Con+T16-169 and TS+T16-169 groups were damaged in different degrees,and the damage of TS+T16-169 group was the most serious.Conclusion The K.pneumoniae from spaceflight significantly increases the expression of inflammatory cytokines in lung tissue and plasma concentrations after infecting tail-suspension mice,and induces more serious damages to the lung tissue,which suggests that inflammatory reactions can be increased in tail suspension mice infected by K.pneumoniae from spaceflight.

Objective To construct the eukaryotic expression vector pEGFP-N1/IL-37b and analyze the expression of IL-37 gene in THP-1 cells. Methods Total RNA was extracted from human peripheral blood mononuclear cells ( PB-MCs) and the coding region of IL-37b gene was amplified by RT-qPCR. Then, the gene was cloned into pEGFP-N1 eu-karyotic expression vector. After transfected the recombinant plasmid into THP-1 cells, the expression of IL-37 was detec-ted by RT-qPCR and Western blot. Results Double restriction enzyme digestion and gene sequencing showed that IL-37b gene was correctly inserted into the eukaryotic expression vector pEGFP-N1. RT-qPCR and Western blot showed that the IL-37 expression level was increased significantly (P<0. 01) after transfection in THP-1 cells. Conclusions We successful-ly constructed a novel anti-inflammatory cytokine IL-37 eukaryotic expression vector pEGFP-N1/IL-37b, which lays a foun-dation for further study on IL-37 functions and its association with related diseases.

Objective To investigate C‐reactive protein in patients with acute brain injury (CRP) ,platelet (PLT) dynamic chan‐ges and clinical significance .Methods A hospital in 2014-2015 120 cases of acute brain injury ,depending on whether surgery di‐vided into :64 cases of surgical group ,56 cases of non‐surgical group .According to Glasgow Outcome Scale (Glasgow Outcome Score ,GOS) divided into 61 cases of poor prognosis group (GOS 1 -3 scores) ,59 patients with good prognosis (GOS 4 -5 scores) .Another choice the same period 50 cases of healthy control group .After the patients were injured 1 d ,3 d ,7 d dynamic tes‐ting CRP ,PLT levels .Results The surgical group and the non‐surgical group patients after injury 1 d serum CRP levels were sig‐nificantly increased ,decreased gradually after all ,the two groups showed a downward trend ,but the surgery group were decreased slowly ,always maintain a high level ,still significantly at 14 d the control group (P<0 .05) .Patients with non‐surgical group de‐creased significantly ,significantly higher than the decline in the extent of the surgery group (P<0 .05) .Surgical and non‐surgical group patients after injury when PLT 1 d showed no increased after 3d began to rise ,increased significantly when 7 d ,PLT levels were elevated degree of surgical group was significantly higher than the non‐surgical group (P<0 .05) .Good prognosis group and a poor prognosis group ,serum CRP on admission were increased ,and reached a peak after 1 d ,after declining in both groups ,with good prognosis group decreased significantly ,while the poor prognosis group ,no significant decline in CRP levels ,continued high levels of state for a long time When postoperative 7d still significantly higher than the normal level (P<0 .05) .At each time point the poor prognosis group ,serum CRP levels were significantly higher than the good prognosis group (P< 0 .05) .When the good prognosis group and a poor prognosis group was mean change 1d PLT little water ,began to increase after the 3 d were poor progno‐sis group of patients was significantly higher than 7 d PLT good prognosis group (P<0 .05) .Conclusion Patients with acute brain injury CRP ,PLT dynamic changes are certain rules ,is to determine the acute phase of the disease of brain injury and prognosis of change .