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 observe the effects of hsa-miR-124-3p.1 in inhibiting epithelial-mesenchymal transition （EMT）， migration and invasion of human gastric cancer cells induced by transforming growth factor β1 （TGF-β1） by targeting tumor necrosis factor receptor-associated factor 6 （TRAF6）. 【Methods】 A total of 43 gastric cancer tissues and 43 normal para-carcinoma tissues were collected. The human gastric mucosal epithelial cells GES-1 and gastric cancer cells （NCI-N87， MGC-803， BGC-823， SGC-7901， and MKN-45） were cultured. The expressions of miR-124-3p.1 and TRAF6 in tissues and cells were detected by fluorescent quantitative PCR and Western blotting. The targeted relationship between miR-124-3p.1 and TRAF6 was verified by dual-luciferase reporter gene system assay. SGC-7901 cell lines with miR-124-3p.1 and TRAF6 overexpression were constructed. The cells were induced by TGF-β1. The invasion and migration abilities of the cells were evaluated by Transwell chamber assay and scratch test. 【Results】 Compared with normal para-carcinoma tissues and normal gastric mucosal cells， the expression of miR-124-3p.1 was downregulated， while the expressions of TRAF6 mRNA and protein were upregulated in gastric cancer tissues and cells （P<0.05）. Compared with control group， expression of E-cadherin in cells was downregulated， expressions of N-cadherin and Vimentin were upregulated， invasion and migration rates of cells were increased in TGF-β1 group （P<0.05）. Compared with TGF-β1 group， after cells were transfected with miR-124-3p.1 mimic， the expression of E-cadherin was upregulated， the expressions of N-cadherin and Vimentin were down-regulated， and invasion and migration rates of cells were decreased （P<0.05）. Compared with miR-124-3p.1 mimic group， invasion and migration rates of cells were increased in TGF-β1+mimic+TRAF6 group， expressions of TRAF6， N-cadherin and Vimentin were up-regulated， and the expression of E-cadherin was down-regulated （P<0.05）. 【Conclusion】 hsa-miR-124-3p.1 is lowly expressed in gastric cancer. Overexpression of miR-124-33p.1 can inhibit EMT， cell invasion and migration induced by TGF-β1. And the action mechanism may be related to the downregulated expression of TRAF6.

OBJECTIVE:To investigate the effects of Astragalus polysaccharides on heart function and myocardial fibrosis in spontaneously hypertensive rats (SHR) and corresponding mechanism. METHODS:50 SHR were randomly divided into a model group,a captopril tablets group (positive drug,30 mg/kg) and the groups of high,medium and low-dose (100,50,25 mg/kg) Astragalus polysaccharides,with 10 SHR in each group. Another 10 Wistar Kyoto rats were included into the normal group. The rats in the drug administration groups were given corresponding drugs ip,while those in the normal group and the model group were given isometric distilled water ip,once a day,for 12 consecutive weeks. The left ventricular systolic pressure (LVSP),left ventricular end diastolic pressure (LVEDP),left ventricular pressure rise rate (+dp/dtmax) and left ventricular pressure decline rate (-dp/dtmax) of the rats were recorded. The heart mass index (HMI) and left ventricular mass index (LVMI) thereof were deter-mined. The level of hydroxyproline and the mRNA and protein expression of transforming growth factor-β1(TGF-β1)and peroxi-some proliferator-activated receptor-γ(PPAR-γ)in the cardiac muscle tissue thereof were detected. RESULTS:Compared to the nor-mal group,the rats in the model group had lower LVSP,+dp/dtmax and-dp/dtmax,higher LVEDP,HMI and LVMI,as well as high-er levels of hydroxyproline and the mRNA and protein expression of TGF-β1 and lower level of the mRNA and protein expression of PPAR-γ in the cardiac muscle tissue (P<0.01). Compared to the model group,all the above-mentioned indexes of the rats in the group of high-dose Astragalus polysaccharides and the captopril tablets group were significantly improved (P<0.05 or P<0.01);except for LVEDP and the mRNA expression of PPAR-γ,all the above-mentioned indexes of the rats in the group of medi-um-dose Astragalus polysaccharides were significantly improved(P<0.05 or P<0.01);no statistically significant difference(P>0.05) in all the above-mentioned indexes was shown between the model group and the group of low-dose Astragalus polysaccha-rides,except that the-dp/dtmax of the latter was significantly higher and the level of the mRNA expression of TGF-β1 was obvious-ly lower (P<0.05). CONCLUSIONS:Astragalus polysaccharide can improve heart function and myocardial fibrosis in SHR by a mechanism which may be related to downregulating the expression of TGF-β1 and upregulating the expression of PPAR-γin the car-diac muscle tissue.

OBJECTIVE:To provide reference for rational drug use in the clinic. METHODS:Irrational medication orders eval-uated by the Affiliated Cancer Hospital of Zhengzhou University during Oct. 2014 to Sep. 2015 were arrangemented,summarized and analyzed. RESULTS:A total of 515 inpatient medical records were reviewed and analyzed,among which there were 165 unrea-sonable medical records and 185 irrational medication orders. Irrational medical records of general surgery department were the most(38 items,accounting for 23.03%). Irrational drug use mainly included irrational usage and dosage(80.00%),drug use with-out indications or not suit indications (7.57%),inappropriate solvent selection (4.86%). Including 66.22% of single overdose, 18.92% of longer medication duration. CONCLUSIONS:There are many irrational medical orders which should be standardized in our hospital,especially overdose and longer medication duration,which increase financial burden of patient. Pharmacists should strengthen communication with clinicians,and hold rational drug use trainings regularly base on the types of the irrationality. These can help to improve rational drug use and guarantee the safety of drug use.

Objective To study the effect of clinical pharmacist interventions on the rational use of antibiot-ics.Methods 1 000 hospitalized patients before the implementation of intervention in April 2012 to April 2013 (control group)and the other 1 000 cases of hospitalized patients in May 2013 to May 2014 after the implementation of the intervention (study group)were selected,the antibiotics use rate,hospitalization time and cost,cost of using antibacterial drugs were compared between the two groups.Results The antibiotics use rate of the study group was 56.0%(560/1 000),significantly lower than 78%(780/1 000)of the control group,with significant differences between the two groups(χ2 =11.089,P=0.032),the hospitalization time,cost of using antibacterial drugs of the study group were (12.6 ±0.8)days,(912.2 ±13.2)yuan,significantly better than (16.9 ±0.7)days,(1 528.1 ± 32.5)yuan of the control group,with significant differences between the two groups (t=9.892,10.142,P=0.028, 0.014);The two groups of hospitalization expenses showed no statistical significance (t =4.984,P =0.072 ). Conclusion Clinical pharmacist intervention has a positive effect on the application of antibacterial drugs,which can significantly reduce the use of antimicrobial drugs and reduce the hospitalization days.

Objective:To investigate the changes of lung lymphocytes in OVA induced murine asthma model,and study the involvement of NK cells in this process.Methods:C57BL/6J(B6) mice were induced to develop asthma by intrapenitoneal injection of OVA with alum as adjuvant, and then inhalation of nebulized OVA. After collecting serum and Bronchoalveolar Lavage Fluid(BALF),IL-4 level was determined by ELISA. The kinetics of pulmonary lymphocyte recruitment and cytokine release were detected by flow cytometry.Results:IL-4 expression increased in BALF after OVA nebulization, while there was no significant difference in serum. IFN-?,IL-4+NK cells accumulation in lung parenchymal tissues,and exhibited an evident NK2 shift in mice with asthma.Conclusion:NK cell involved in OVA-induced mouse asthma and NK2 shift accompany with Th2, indicating that NK2 played an important role in this process.