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 investigate the value of the extrahepatic bile duct and main pancreatic duct segment patterns on magnetic resonance cholangiopancreatography (MRCP) for differentiating the periampullary carcinoma (PAC).Methods:The clinicopathologic data of 125 patients with PAC who were admitted to Wuxi No.2 People’s Hospital from June 2013 to December 2021 were retrospectively analyzed, including 72 males and 53 females, aged (64.9±8.6) years. According to its anatomy, the extrahepatic bile duct (B) was divided into suprapancreatic and intrapancreatic (including ampullary) segments, and the main pancreatic duct (P) was divided into tail-body and head segments. MRCP patterns: i. the extrahepatic bile duct or main pancreatic duct visible without dilatation, ii. cutoff of the distal extrahepatic bile duct or main pancreatic duct with upstream dilatation, iii. cutoff of the intrapancreatic or head segment with upstream dilatation and remnant intrapancreatic or head segments invisible, iv. cutoff of the intrapancreatic or head segment with upstream dilatation and nondilated remnant intrapancreatic or head segments, were represented as 0, 1, 2, and 3, respectively. Segment patterns of B1/P0+ B1/P1, B0/P2+ B0/P3+ B2/P2+ B2/P3+ B3/P3, B3/P0, and B0/P0+ B2/P0 on MRCP were compared in PAC patients.Results:Of the 125 patients, there were 57 (45.6%) with pancreatic head carcinoma, 36 (28.8%) with ampullary carcinoma, 20 (16.0%) with distal cholangiocarcinoma, and 12 (9.6%) with periampullary duodenal carcinoma. Segment patterns of B0/P2+ B0/P3+ B2/P2+ B2/P3+ B3/P3 were found in 52 patients with pancreatic head carcinoma (91.2%, 52/57), with a significant difference between PAC (χ 2=110.66, P<0.001). Segment patterns of B1/P0+ B1/P1were found in 36 patients with ampullary carcinoma (100.0%, 36/36), fallowed by 11 (91.7%, 11/12) with periampullary duodenal carcinoma, with a significant difference between PAC (χ 2=129.95, P<0.001). Segment pattern of B3/P0 presented in 16 patients with distal cholangiocarcinoma (80.0%, 16/20), with a significant difference between PAC (χ 2=62.45, P<0.001). The segment patterns of B0/P0+ B2/P0 were only seen in 3 of 57(5.3%) patients with pancreatic head carcinoma. Conclusion:On MRCP, cutoff of the head segment with upstream dilatation and remnant head segment invisible or nondilated indicates the pancreatic head carcinoma. Cutoff of the intrapancreatic segment with upstream dilatation, remnant intrapancreatic segment visible, and main pancreatic duct nondilated, indicates the distal cholangiocarcinoma. And cutoff of the distal extrahepatic segment with upstream dilatation and main pancreatic duct dilatation or not, indicates the ampullary or periampullary duodenal carcinoma.

Objective:To summarize the clinical characteristics of children with rheumatic disease combined with endocrine disorder.Methods:A retrospective analysis was performed on the clinical data, including sex, age, clinical presentation, laboratory tests, treatment and outcome, of 13 patients with rheumatic diseases combined with endocrine disorder, who were admitted to our department in Children′s Hospital, Capital Institute of Pediatrics from January 2014 to December 2020.Results:Among the 13 cases, 3 were males and 10 were females, without family history. Their age was (10±4) years. And the average course of disease was 4.1 months. Eight of them were diagnosed with systemic lupus erythematosus (JSLE), 2 with juvenile idiopathic arthritis (JIA), 1 with childhood vasculitis, 1 with juvenile-onset systemic sclerosis (JSSc) and 1 had juvenile dermatomyositis (JDM). Regarding the initial presentation, 10 cases had symptoms of rheumatic disease, 2 had polydipsia and polyuria, and 1 had goiter. All the 13 patients had multiple system involvement. Regarding endocrine disorder, 10 had thyroiditis or subclinical thyroiditis, 4 had diabetes mellitus and one had both thyroid and pancreas involvement. Thyroid stimulating hormone in 10 patient with thyroid involvment was 19.6 (5.2-34.0) mU/L, and their total thyroxine was 75.3 (45.2-105.4) nmol/L. Besides, thyroid peroxidase antibody or thyroglobulin antibody was positive in 7 cases. The blood glucose of 4 children with pancreatic injury was 25.0 (17.0-33.0) mmol/L, and C-peptide was 0.4 (0.3-0.5) mg/L. Glutamate dehydrogenase antibody, protein tyrosine phosphatase antibody and zinc transporter 8 antibody were positive in two cases. After treatement with immunosuppressant or immunoglobulin combined with glucocorticoid or nonsteroidal antiinflammatory drugs for rheumatic symptoms, and levothyroxine or insulin for endocrine diseases, they were all followed up for more than 6 months and maintained clinical stability.Conclusions:Rheumatic diseases in children can be complicated with endocrine disorders, and the involved organs are usually thyroid and pancreas. In children with rheumatic disease, thyroid injury usually has subtle onset, whereas pancreas injury develops rapidly, even life-threatening. Insulin should be used persistently under the instruction of endocrinologist.

Objective: To improve the understanding and diagnosis and treatment level of infant with Takayasu arteritis (TA) by analyzing the clinical features of 14 pediatric patients and reviewing related articles. Methods: The clinical and follow-up data of infants with TA who were admitted to the Children′s Hospital Affiliated to Capital Institute of Pediatrics between July 2016 and May 2019 were retrospectively analyzed.By reviewing related articles, the clinical features of this disease were summarized. Results: The age of 14 patients (including 6 males and 8 females) were between 1 month and 23 days and 28 months.The most common clinical manifestations were fever in 10 cases (71.4%), hypertension in 9 cases (64.3%), weak or no pulse in 5 cases (35.7%). According to the clinical type of lesion vessels, 11 cases (78.5%) were generalized type, 3 cases (21.4%) were brachiocephalic artery type, and there was no thoracic abdominal aorta or single pulmonary artery type in this group.Among 14 infants with TA, 12 cases had common carotid artery, carotid artery, subclavian artery, coronary artery and its branches (anterior descending branch, circumflex branch) involved (85.7%); 11 cases had renal artery involved (78.6%); 9 cases had radial artery involved (64.2%); 8 cases had abdominal aorta involved (57.1%); 6 cases had descending aorta involved (42.9%); 6 cases had thoracic aorta involved (42.9%); 6 cases had superior mesenteric artery involved (42.9%); 5 cases had femoral artery involved (35.7%); 5 cases had pulmonary artery involved (35.7%); and 4 cases had brachial artery involved (28.6%). In those 14 patients, 11 cases were misdiagnosed, and 3 cases had unclear diagnosis, with misdiagnosis duration of 18 days to 2 months.In misdiagnosed cases, 8 cases were misdiagnosed as atypical Kawasaki disease.Among those 14 cases, the ranges of most lesions were gradually decreased, and the slightly involved vessels even completely returned to normal state after treatment in 7 cases.The vascular imaging showed no significant exacerbation or improvement in 4 cases.Nine cases developed hypertension, the blood pressure of whom could be controlled within normal range with hypotensive drugs which could not be interrupted.Physical examination found weak or no pulse in 5 cases who were not improved.Among 14 patients, 7 cases showed normal development, while the height and body mass of another 7 cases were the 25^th percentile below those of normal children of the same age.All 14 patients were followed up for 2-22 months and received regular treatment without recurrence. Conclusions TA patients aged less than 3 years tend to have more blood vessels involved, be in serious condition and have higher rate of misdiagnosis.The disease can be controlled quickly after treatment, but vascular diseases may be developed easily.Some patients have a poor prognosis.

Objective: To evaluate the value of serum cytokine level in the efficacy of tocilizumab for the treatment of systemic-onset juvenile idiopathic arthritis. Methods: 30 cases with SoJIA hospitalized in Capital Institute of Paediatrics from June 2016 to October 2018 were treated with Interleukin-6 receptor antagonist(tocilizumab) injection. Among them, 20 were males(67%) and 10 were females(33%). The age at diagnosis was between 0.84 to 13years. Whiteblood cell, C-reactive protein, erythrocyte sedimentation rate, serum interleukin(IL-6, IL-2R, IL-8, IL-10, IL-1β) and tumor necrosis factor-alpha levels were observed before treatment, after the 2nd week, after the 6th week and after the 22nd week.Mann-Whitney nonparametric test and Chi-square test were used to analyze the data of cytokines pre and after-treatment. Results: All of the 30 cases had fever before medication. The fever disappeared in 28 cases after using tocilizumab. One case stopped using tocilizumab because of allergic reaction and one case stopped because of poor efficacy. Among 28 cases with normal body temperature after medication, the arthritis and rash manifestations were significantly improved. WBC, AESR and CRP were all lower than those before medication. Within these 28 cases, the serum IL-6 level was168.50(67.40-589.25) pg/mL pre-treatment, 107.50(28.03-281.50) pg/mL after the 2nd week. There was no statistical difference between them(Z=-1.754, P>0.05). The serum IL-6 level was 64.05 (19.90-130.75) pg/mL after the 6th week and 24.80 (3.45-95.40) pg/mL after the 22nd week. Compared with pre-treatment, they were all lower than pre-treatment levels(Z=-2.942,-3.334,P<0.01,<0.01).Serum IL-2R level was 740.50(510.00-1 161.00)U/mL after the 2nd week, 796.50 (534.00-1 008.00) U/mL after the 6th week and 688.00 (527.00-889.50) U/mL after the 22nd week. Compared with pre-treatment [1 322.50(812.00-1 659.00)U/mL], they were all lower than pre-treatment levels (Z=-2.818,-3.130,-3.466, P<0.01, <0.01, <0.01). Serum TNF-alpha level was 23.70 (20.30-41.23) pg/ml after the 2nd week, 26.75(16.83-47.03) pg/ml after the 6th week,18.60(13.10-34.90) pg/ml after the 22nd week. Compared with pre-treatment [26.50(20.55-37.43) pg/ml], there were no statistical difference between after and pre-treatment(Z=0,-0.560,-1.954,P>0.05,>0.05,>0.05). Serum IL-8 level was 200.85(95.43-364.00)pg/ml after the 2nd week, 194.50(50.75-433.00)pg/ml after the 6th week, 161.50 (38.98-308.00)pg/ml after the 22nd week. Compared with pre-treatment [96.20(59.75-371.75) pg/ml], there were no statistical difference between after and pre-treatment(Z=-0.86,-0.131,-0.186,P>0.05,>0.05,>0.05). There was no statistical difference between after the 2nd week and pre-treatment in the IL-10 level(χ²=2.33, P>0.05). The IL-10 level after 6th week and after 22nd week were all lower than pre-treatment levels(χ²=4.08, 4.08, P<0.05, <0.05). There were no statistical difference between after and pre-treatment(χ²=0.084, 2.504,3.818,P>0.05,>0.05,>0.05)in IL-1β level. Conclusion After treatment with tocilizumab, the levels of serum IL-6 and IL-2R are helpful to assess the activity of SoJIA and the efficacy of therapy.

Objective: To investigate the early typing diagnostic and predictive value of anti-keratin antibodies(AKA), anti-perinuclear factor(APF) and anti-citrullinated protein antibodies(ACPA) in patients of juvenile idiopathic arthritis (JIA). Methods: A retrospective study was conducted to collect 144 cases of JIA who were hospitalized in Capital Institute of Pediatrics from December 2013 to June 2016 and followed up for at least one year.Among them,66 were males (46%) and 78 were females (54%).The age at diagnosis was between 1 year 5 months to 15 years 9 months.144 patients were tested for AKA,ACPA,APF and TNFα upon admission. Chi-square test or Fisher exact test were used to compare the positive rates of three antibodies among different subtypes. Mann-Whitney nonparametric test and Chi-square test or Fisher exact test were used to analyze the data of prognosis between antibody-positive group and antibody-negative group in the course of disease. Results: In 144 patients, 49(34%) were classified as systemic arthritis, 28 (19.4%) as polyarthritis, 61(42.3%) as oligoarthritis, and 6(4.2%) as enthesitis-associated arthritis. 52 cases (36.1%) were positive for one antibody or more antibodies of AKA/APF/ACPA at the early stage, 14(9.7%) were AKA positive, 44(30.6%) were ACPA positive and 12(8.3%) were APF positive. The positive rates of ACPA/AKA/APF antibodies were significantly different among different subtypes(χ²=33.863,26.860,14.395; P<0.01,<0.01,<0.05).The rates in polyarthritis were higher than those in systemic arthritis and oligoarthritis; In 95 children with non-systemic form, the level of TNFα in antibody-positive group (43 cases) was higher than that in antibody-negative group (52 cases) at the early stage(Z=4.785, P<0.01);144 patients were followed up for at least one year,the rates of patients who accepted biologic therapies were significantly different between antibody-positive group and antibody-negative group (50% vs 25%). So do the rates of patients with joint deformities (17.3% vs 2.2%) and with important joints involvement (hip and axis joints) (59.6% vs 14.1%) (χ²=9.249,10.875,32.392; P<0.01,<0.01,<0.01). Further more, the number of joints involved in the antibody-positive group (7.07±3.85) was significantly more than that in the antibody-negative group (2.31±1.64) (F=63.822, P<0.01). Conclusions AKA,APF and ACPA are important in the early typing diagnosis of JIA,and may be closely related to the prognosis of patients with JIA.

Objective: To analyze the clinical characteristics and infection of children with Takayasu′s arteritis(TA) for improving the awareness of the disease. Methods: A retrospective study was performed on the 24 children with TA in our hospital. Results: The average onset age was 9.3±3.2 years old, the ratio of male to female was 1∶3. The most common TA type was thoracic abdominal aortic type (54.2%) in clinical classification. The initial symptoms included high blood pressure, dizziness/headache, fever and fatigue, etc.Six cases (25%) had tuberculosis infection, including 1 case of tuberculosis. There are 3 patients (8.3%) with elevated O levels, 2 patients (8.3%) with EB virus infection and 1 patient (4.2%) with small viral B19 infection. Conclusions The onset of TA in children is complicated. It is important to take examinations carefully for early diagnosis, avoiding delay treatment and bad prognosis.

Objective: To summarize the clinical data of 15 patients with fibrodysplasia ossificans progressiva (FOP), follow up and analyze the characteristics of the joint involvement in FOP. Method: From May 2005 to December 2016, fifteen FOP cases had been diagnosed in the Children′s Hospital Capital Institute of Pediatrics. All medical records and follow-up data were collected and a retrospective analysis was made on the joint involvement in FOP. Pearson correlation analysis was used for data, P<0.05 for the difference was statistically significant. Result: There were 8 males and 7 females in 15 cases. The age of onset was 2(1-6)years. The age at diagnosis was 6 (4-9) years. All cases had hallux valgus deformity and bone mass formation. Twelve cases had joints involvement on enrollment into this study: 8 cervical vertebra, 7 shoulder joint, 5 hip joint, 4 elbow joint, 3 wrist joint, 2 temporomandibular joint, 2 lumbar vertebra. The age of diagnosis and duration of disease were positively correlated with the number of the involved joints (r=0.523, 0.628; P=0.045, 0.012); mild changes were found in joint imaging. Thirteen cases received telephone follow-up, the average duration of follow-up was 6(3-7)years, no change in 11 cases, disease progress in 2 cases. Conclusion Joint involvement is a common complication of FOP, especially the cervical vertebra.Multiple joints involvement, dominant functional impairment, and mild imaging changes are the characteristics of joint lesions caused by FOP.The number of involved joints gradually increases with increase of age of the patients and the prolonged course of the disease.

AIM:To explore the effect of dasatinib on the viability, migration, cell cycle and apoptosis of human bone marrow mesenchymal stem cells (hBMSCs), as well as the underlying signal pathway to evaluate the influence of dasatinib on hematopoietic microenvironment clinically.METHODS:The cell viability was measured by CCK-8 assay.The migration ability was detected by wound healing assay.The cell cycle and apoptosis were analyzed by flow cytometry.Acridine orange/ethidium bromide staining was also used to detected apoptosis.The secretion of transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) were measured by ELISA.The protein levels of cleaved caspase-3, protein kinase B (Akt) and phosphorylated Akt were determined by Western blot.RESULTS:Compared with control group, dasatinib at 1~10 nmol/L suppressed the viability and migration ability of hBMSCs, and dasatinib at concentration of 7 nmol/L was adopted in the following assays.Dasatinib promoted apoptosis, and blocked the cell cycle in G1 phase.In addition, the secretion of TGF-β1 and TNF-α was increased markedly.The protein levels of cleaved caspase-3 was increased, but the protein levels of Akt and phosphorylated Akt were decreased.CONCLUSION:Dasatinib inhibits the viability and migration ability of hBMSCs in a dose-dependent manner, promotes the secretion TGF-β1 and TNF-α, and induces cell cycle arrest and apoptosis.Dasatinib might regulate the biological behaviors of hBMSCs observed above by modulating the expression and phosphorylation of Akt.

Objective: To evaluate the efficacy and side effects of tocilizumab for the treatment of systemic juvenile idiopathic arthritis. Method: In this prospective self case-control study, the children diagnosed with refractory systemic juvenile idiopathic arthritis admitted to Department of Rheumatism and Immunology of Children's Hospital Affiliated to Capital Institute of Pediatrics from December 2013 to June 2016 were enrolled and information before and after treatment of tocilizumab was analyzed. The tocilizumab was introvenously guttae in a dose of 8-12 mg/kg every 2 weeks. Complete blood count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were tested before and after the application of tocilizumab. Detailed clinical manifestations were recorded. All results were analyzed by χ² test and t test. Result: Forty patients with a median age of (6.6±3.7) years were enrolled, including 15 males and 25 females. All of the patients presented with fever and 38 patients got normal temperature 24-48 hours after treatment with tocilizumab. Symptoms disappeared in 13 and improved in 4 patients after treatment among the 17 patients who presented with arthritis. Within the 10 patients who manifested with rashes, 9 patients' rashes disappeared without relapse accompanied by the normalization of temperature after the treatment of tocilizumab. One patient got normal temperature but intermittently emerged rashes after symptoms of arthritis improved. In the 40 patients, 38 well tolerated tocilizumab while 2 showed rashes and chill which disappeared shortly after antianaphylaxis treatment. No severe treatment-related infection was found in any patients. According to the study, the white blood cell counts(×10⁹/L), CRP(mg/L) and ESR(mm/1h) tested 2 weeks after the treatment with tocilizumab were significantly lower than that before treatment(12.1±1.2 vs. 16.5±1.8, 47±8 vs. 67±9, 21±5 vs. 57±6, t=2.75, 3.98, 5.22, P=0.009, 0, 0, respectively). No significant changes were found in concentration of IL-6 and TNF-α (65(207) vs. 45(137) ng/L, and 14(6) vs. 17(19)ng/L, Z=-1.247 and-1.285, P=0.212 and 0.199 respectively). Conclusion Tocilizumab is a treatment with good efficacy and safety for refractory systemic juvenile idiopathic arthritis. Adverse effects would be found in some patients.