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

BACKGROUND:Studies have shown that there is a close association between spinal cord injury and ferroptosis,and that tetramethylpyrazine has the function of regulating redox reactions. OBJECTIVE:To investigate the regulatory effect of tetramethylpyrazine on ferroptosis in rats with spinal cord injury and its mechanism. METHODS:Thirty-six female specific pathogen-free Sprague-Dawley rats were randomly divided into sham-operated group,model group and tetramethylpyrazine group,with 12 rats in each group.Animal models of spinal cord injury were established using the modified Allen's method in the latter two groups.No treatment was given in the sham-operated group,while rats in the model and tetramethylpyrazine groups were given intraperitoneal injection of normal saline and tetramethylpyrazine solution,once a day,for 28 days. RESULTS AND CONCLUSION:The Basso,Beattie&Bresnahan Locomotor Rating Scale score in the tetramethylpyrazine group was lower than that in the sham-operated group but higher than that in the model group after 14,21,and 28 days of treatment(P＜0.05).After 28 days of treatment,hematoxylin-eosin staining showed that in the model group,the spinal cord tissue of rats showed cavity formation,necrotic tissue and inflammatory infiltration with fibrous tissue formation;in the tetramethylpyrazine group,the area of spinal cord tissue defects was smaller,and inflammatory infiltration and fibrous tissue formation were less than those in the model group.After 28 days of treatment,Prussian blue staining showed that a large amount of iron deposition was seen in the spinal cord tissue of rats in the model group,and less iron deposition was seen in the spinal cord tissue of rats in the tetramethylpyrazine group than in the model group.After 28 days of treatment,the levels of glutathione and superoxide dismutase in the rat spinal cord tissue were decreased(P＜0.05)and the level of malondialdehyde was increased in the model group compared with the sham-operated group(P＜0.05);the levels of glutathione and superoxide dismutase in the rat spinal cord tissue were increased(P＜0.05)and the level of malondialdehyde was decreased in the tetramethylpyrazine group compared with the model group(P＜0.05).After 28 days of treatment,qRT-PCR and western blot assay showed that the mRNA and protein levels of glutathione peroxidase 4,ferritin heavy chain,and ferroportin in the rat spinal cord tissue in the model group were decreased compared with those in the sham-operated group(P＜0.05),while the mRNA and protein levels of glutathione peroxidase 4,ferritin heavy chain,and ferroportin in the rat spinal cord tissue in the tetramethylpyrazine group were increased compared with those in the model group(P＜0.05).Immunofluorescence staining showed that after 28 days of treatment,the neuronal nuclei positive staining in the spinal cord of rats was the most in the sham-operated group and the least in the model group.To conclude,tetramethylpyrazine can improve motor function and play a neuroprotective role in rats with spinal cord injury by regulating ferroptosis.

Objective:To study the effects of tetramethylpyrazine on the expressions of ferroptosis related molecules after spinal cord injury; To explore the mechanism of tetramethylpyrazine promoting the repair of spinal cord injury (SCI).Methods:Totally 36 SD rats were divided into sham-operation group, model group and tetramethylpyrazine group according to random number table method, with 12 rats in each group. The rats in the sham-operation group underwent laminectomy without injury to the spinal cord. The SCI model was prepared in the other two groups. The rats in the tetramethylpyrazine group were intraperitoneally injected with tetramethylpyrazine of 80 mg/kg, and the rats in the sham-operation group and model group were intraperitoneally injected with the same volume of normal saline, once a day, continuous intervention for 28 days. One day before operation and 1, 3, 5, 7, 14, 21, 28 days after operation, BBB limb motor function score was used to evaluate the limb motor function of rats. Nissl staining was used to observe the morphology of neurons. Prussian staining was used to observe iron deposition. Assay kit was used to detect the contents of MDA and ROS in spinal cord tissue. Western blot was used to detect the protein expressions of xCT, GPX4 and ACSL4, and qPCR was used to detect the mRNA expressions of mRNA of xCT, GPX4 and ACSL4.Results:On the 14th, 21st and 28th days after operation, compared with the model group, the BBB score of tetramethylpyrazine group increased ( P<0.01); tetramethylpyrazine could significantly improve the morphology and structure of neurons and reduce the iron content in spinal cord tissue; compared with the model group, the contents of MDA and ROS in the spinal cord tissue of tetramethylpyrazine group decreased ( P<0.01); the levels of xCT and GPX4 mRNA and protein increased ( P<0.01), while the expression of ACSL4 mRNA and protein decreased ( P<0.01). Conclusion:Tetramethylpyrazine can regulate lipid peroxidation by regulating the expressions of ferroptosis related molecules, which is conducive to the recovery of limb motor function in rats with spinal cord injury.

OBJECTIVE： To establish a method for rapid determination of total phenylethanoid glycosides and total iridoid glycosides in the root of Rehmannia glutinosa. METHODS： The contents of total phenylethanoid glycosides and total iridoid glycosides in medicinal material samples were determined by UV spectrophotometry. Quantitative model of total phenylethanoid glycosides and total iridoid glycosides in medicinal samples was established by NIRS-PLS method. The optimal pretreatment spectra were multivariate scattering correction combined with first derivative method， standard normalization combined with first derivative method. The optimum spectral ranged from 6 703.35-11 065.54 cm－1 and 3 999.63-9 102.36 cm－1. The optimum principal factor number were 10 and 7. RESULTS： The content determination of total phenylethanoid glycosides and total iridoid glycosides in medicinal material samples was proved to meet the requirements by methodological experience. The internal cross validation determination coefficients of total phenylethanoid glycosides and total iridoid glycosides were 0.998 2 and 0.980 9. The correction of root mean square error was 0.032 7 and 0.186 0. The root mean square error of prediction were 0.035 5 and 0.035 1. The root mean square error of cross validation were 0.256 9 and 0.574 3. The predicted values of total phenylethanol glycosides and total iridoid glycosides were 0.268％-1.636％ and 3.424％-6.978％， respectively； the determination value of them were 0.299％-1.629％ and 3.431％-6.952％， respectively； the absolute deviations were －0.042％-0.067％ and －0.111％-0.088％， respectively；the relative deviations were －0.819％-0.076％、－2.257％-1.672％， respectively；There was no statistical significance between predicted values and measured values （P＞0.05）. CONCLUSIONS： The method is accurate and simple. The method can be used for the rapid determination of total phenylethanoid glycosides and total iridoid glycosides in different germplasms of R. glutinosa.

Objective To investigate the causes and treatments for the congestion after pig-tail catheter drainage of liver abscess.Methods Clinical data of 3 patients with complicated liver abscess admitted to Tangdu Hospital of Air Force Military Medical University from April 2016 to January 2017 were retrospectively analyzed.The informed consents of all patients were obtained and the local ethical committee approval was received.Case 1,male,aged 84 years;Case 2,female,aged 57 years;Case 3,female,50 years.The pig-tail catheter was clogged after being placed in 3 patients for drainage and the drainage catheters were therefore rotated clockwise or counter clockwise.Results After multiple rotations,the head end of drainage catheter was loosened and unclogged and necrotic tissues was drained out.Mild or moderate fever was observed in cases 1 and 3 after rotating the pig-tail catheter,which was relieved spontaneously.3 patients presented with mild bleeding after rotating the catheter and no significant change was noted in Hb.After the drainage catheter was unobstructed,the fever was relieved and all were cured and discharged.No recurrence was observed at postoperative 1 year.Conclusions For the intractable congestion of pig-tail catheter in liver abscess patients,rotating and loosening the catheter can be a good appoach.

Objective To investigate the diagnostic and treatment results of arteriovenous fistula of cauda equina.Methods From January 2000 to December 2015,9 Patients with arteriovenous fistula of cauda diagnosed and treated at the Department of Neurosurgery,Xuanwu Hospital,Capital Medical University were enrolled retrospectively,including 6 males and 3 females.Their ages were 17-58 (mean 39±14) years.The diagnoses were confirmed by digital subtraction angiography (DSA) or surgery (the lesions were located on the cauda equine,which were fed by the arterial supply of the nerve root,and the drainage vein flowed upward into the perimedullary vein).The clinical data,imaging data,and treatment follow-up results of the patients were analyzed.Results The patients presented with weakness of both lower extremities and disturbances of bowel movement and urination.Aminoff Logue score for spinal function was 7.2±3.2 before procedure.The median course of disease was 6.0 (4.5-18.0) months.Angiography showed that the vascular architecture types of the lesions were divided into simple fistula type and micro-nidus type.The feeding arteries were all the nerve root branches of the internal iliac artery.Three patients complicated with conical part of the intramedullary arteriovenous malformations.Eight patients were treated with endovascular embolization,one was treated by operation.No patients were treated with combined interventional surgery,and no surgery-related complications were observed.The mean follow-up duration was 20.1±6.7 months.Imaging follow-up showed that they all reached anatomic cure.Aminoff Logue score dropped to 4.6±2.8 after treatment.There were significant differences before and after treatment in Aminoff Logue score of the patients (t=4.276,P<0.05).Conclusions The nerve root arteriovenous fistula of the cauda equina can be diagnosed by DSA findings.Symptomatic patients are eligible for the indication of endovascular or surgical treatment.Anatomy and functional prognosis are satisfactory after treatment.

Objective · To investigate the difference in myocardial strain of left ventricle between obstructive hypertrophy cardiomyopathy (HCM) and nonobstructive HCM. Methods · Cardiac magnetic resonance imaging (MRI) exam was performed on 48 sequential enrolled patients with HCM (18 with obstructive HCM, and 30 with nonobstructive HCM), whose left ventricular ejection fractions (LVEF) were over 50%. Twenty-five healthy volunteers were examined as normal controls. Global longitudinal strain (GLS), global radial strain (GRS), global circumferentialstrain (GCS), LVEF, left ventricular end diastolic volume (LVEDV), left ventricularmass (LVM), left ventricular end diastolic volume index (LVEDVI), and left ventricular mass index (LVMI) were collected and compared. Radial strain, circumferential strain and peak radial displacement were also measured in medial segment of left ventricle according to American Heart Association (AHA) 17-segment model. Results · ① LVEF of the patients with obstructive HCM was bigger than those of nonobstructive HCM patients and control group (P<0.05). LVM and LVMI of the HCM groups were bigger than those of control group (P<0.01). ② Left ventricle GLS, GRS, and GCS significantly decreased in the patients with nonobstructive HCM compared to those with obstructive HCM (P<0.05). The three parameters of two HCM groups were significantly lower than those of healthy volunteers (P<0.05). ③ Compared with obstructive HCM patients,the segmental parameters of left ventricule, the medial segment circumferential strain and radial strain of nonobstructive HCM patients significantly decreased (P<0.05), and the two parameters of both HCM groups were lower than those in healthy volunteers. Compared with obstructive HCM patients and healthy volunteers, peak radial displacement of left ventricule medial segment in nonobstructive HCM witnessed a significant decrease, while no significant difference was observed between obstructive HCM patients and healthy volunteers. Conclusion · In the LVEF preserved HCM patients, the myocardial strain of left ventricle in nonobstructive HCM patients decrease significantly than that in obstructive HCM patients, which may result in the different clinical outcomes intwo types of HCM patients. It is suggested that the myocardial strain is more sensitive than ejection fraction in the evaluation of myocardial performance of HCM patients.

Objective To investigate the feasibility and superiority of video-assisted thoracic surgery (VATS) in the diagnosis and treatment of chest trauma feasibility and superiority.Methods 60 cases were randomly selected and divided into the observation group (n =30) and control group (n =30) by random number table.The observation group was treated with VATS and the control group was treated with traditional methods.Incision length,after the first three days of pain,blood transfusion,closed drainage time,drainage,postoperative hospital stay,postoperative day 7 1S forced expiratory volume (FEV1) and other related indicators were compared between the two groups.Results Incision length of the observation group was (7.41 ± 5.52) cm,which was significantly shorter than (18.62 ± 4.11) cm of the control group (t =7.54,P ＜ 0.05).Amount of blood transfusion and drainage of the observation group were (199.88 ± 23.00) mL and (199.52 ± 18.48) mL,which were significantly less than (465.67 ± 41.88) mL and (560.02 ± 44.98) mL of the control group (t =6.38,6.98,all P ＜ 0.05).In the observation group patients after the first three days VAS score was (3.61 ±0.20) points,lower than (6.01 ±0.25) points of the control group (t =6.64,P ＜ 0.05).Postoperative hospital stay was (6.50 ± 0.45) d,shorter than (11.33 ± 0.50) d of the control group(t =7.95,P ＜0.05).Conclusion VATS has the advantages of intuitive and strong,trauma,pain,faster recovery,shorter hospital stay,less closed thoracic drainage,fewer complications and so on in chest injury diagnosis and treatment.

Objective To investigate the effect of cobalt chromium alloy onlay on the direct repair of cracked vital pulp teeth with the resin compostie filling and porcelain-fused-to-metal (PFM ) crown repair as the control .Methods 201 cracked vital pulp teeth from 201 cases were randomly divided into 3 groups according to the clinical symptoms :mild discomfort at occlusion (group A) ,pain at occlusion accompanied with transient pain to cold or hot stimulation (group B) and pain at occlusion accompanied with continuous pain to cold or hot stimulation(group C) .The cracked teeth directly were restored by the resin composite filling ,cobalt chromium alloy onlay and PFM crown repair and the effective rate in each group was observed after 2-year follow up .Results The effective rate of the group A ,B and C were statistically significant different from each other (P<0 .05) .The effective rate of the co-balt chromium alloy onlay and the PFM crown was statistically significant higher than that of resin composite (P<0 .05) .Conclusion The direct repair with cobalt chromium alloy onlay is an effective repair method for the cracked vital pulp teeth with mild discomfort at occlusion and mild pain accompanied with transient pain to cold or hot stimulation .

Objective To explore the prognosis and its related factors of three-dimensional conformal radiotherapy (3D-CRT) for elderly patients with esophageal carcinoma. Methods From January 2001 to August 2007, 89 elderly patients aged 65 years or more with esophageal carcinoma were treated with 3D-CRT. And the local control rates, survival rates and its related prognostic factors were evaluated retrospectively, using SSPS11.5 software. Results The 1-, 2-, 3-and 4-year local recurrence-free survival rates were 65.2%, 43.0%, 27.3% and 22.3%, respectively. The 1-,2-, 3-and 4-year overall survival rates were 68.5%, 48.8%, 36.8% and 25.2%, respectively. And the median survival time was 21.5 months. With univariate analysis, the significant prognostic factors included the different diet before radiotherapy (χ~2=6.26, P=0. 012), T stage (χ~2=8. 80, P=0. 003), N stage (χ~2=4.33, P=0. 038), clinical stage (χ~2=7.88, P=0. 005), the largest diameter of tumor in CT scanning image (χ~2=10.88, P=0.004), recent efficacy (χ~2=5.28, P=0. 022) and chemotherapy (χ~2=5.49, P=0.019). And the factors which were not related with prognosis included gender (χ~2=0.74, P=0. 390), age (χ~2=1.89, P=0. 170), lesion length showed by esophageal angiography (χ~2=2. 38, P=0.123), lesion length showed by CT (χ~2=2.69, P=0.101),primary tumor site (χ~2=2.12, P=0. 146), coexistent disease (χ~2=0. 03, P=0. 874), exposure mode (χ~2=0.04, P=0.847) and radiation dose (χ~2=0. 24, P=0. 627). Multivariate analysis revealed that the different diet before treatment (P=0. 002), the clinical stage (P=0. 007) and chemotherapy (P=0. 011) were independent prognostic factors. Radiation induced esophagitis was observed in 20 cases in grade 0, 30 cases in grade 1, 32 cases in grade 2, 7 cases in grade 3. And acute radiation pneumonitis was observed in 89 patients, with 57 in grade 0, 20 in grade 1, 8 in grade 2, 2 in grade 3 and 2 in grade 5. Until the end date of follow-up, 60 patients had died: 29 cases died of local recurrence or uncontrolled disease, 11 cases died of metastasis, 5 cases died of local recurrence with metastasis, and 15 cases died of other reasons. Conclusions 3D-CRT can be considered as an effective and feasible approach for elderly patients with esophageal cancer. The 3D-CRT provides them with less obstruction of diet, early clinical stage and longer survival time. 3D-CRT combined with chemotherapy may improve survival rate.