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 effect of autologous osteochondral tissue and periosteum transplantation on tendon-bone healing of rotator cuff in rabbits. METHODS: Twenty-four male New Zealand white rabbits were randomly divided into autologous osteochondral tissue and periosteum transplantation group (experimental group, n=12) and simple suture group (control group, n=12). Both groups were subjected to acute supraspinatus tendon injury and repaired with corresponding techniques. At 4, 8, and 12 weeks after operation, 4 specimens from each group were taken from the right shoulder joint for histological examination (HE staining, Masson staining, and Safranin O-fast green staining), and the left shoulder was subjected to biomechanical tests (maximum tensile load and stiffness). RESULTS: Both groups of animals survived until the completion of the experiment after operation. At 4 weeks after operation, both groups showed less collagen fibers and disorder at the tendon-bone junction. At 8 weeks, both groups showed reduced inflammation at the tendon-bone junction, with more organized and denser collagen fibers and chondrocytes. The experimental group showed better results than the control group. At 12 weeks, the experimental group showed typical tendon-bone transition structure, with increased generation of collagen fibers and chondrocytes, and the larger cartilage staining area. Both groups showed an increase in maximum tensile load and stiffness over time ( P<0.05). The stiffness at 4 weeks and the maximum tensile load at 4, 8, and 12 weeks in the experimental group were superior to control group, and the differences were significant ( P<0.05). There was no significant difference in stiffness at 8, 12 weeks between the two groups ( P>0.05). CONCLUSION Autologous osteochondral tissue and periosteum transplantation can effectively promote the fiber and cartilage regeneration at the tendon-bone junction of rotator cuff and improve the biomechanical effect of shoulder joint in rabbits.
Animals ; Rabbits ; Male ; Wound Healing ; Transplantation, Autologous ; Periosteum/transplantation* ; Rotator Cuff Injuries ; Rotator Cuff/surgery* ; Tendons/surgery* ; Biomechanical Phenomena ; Chondrocytes/transplantation* ; Tendon Injuries/surgery* ; Tensile Strength

Objective To investigate the relationship between the expression of cyclophilin B(PPIB)in glioma and clinicopatholog-ical features,patient survival,and the infiltration of tumor-associated macrophages.Methods Based on the Cancer Genome Atlas(TCGA)database,the expression of PPIB in normal,low-grade,and high-grade gliomas was compared,and the expression of PPIB in glioma pathological tissues was detected by immunohistochemical staining.Based on the clinical case data of TCGA database,the relation-ship between PPIB expression and clinicopathological features of glioma was analyzed.Kaplan-Meier method was used to evaluate the im-pact of PPIB expression differences on the survival of glioma patients.Immunofluorescence method was used to analyze the expression of PPIB in the pathological tissues of glioma and its correlation with the infiltration of tumor-associated macrophages.Results The expres-sion of PPIB in high-grade glioma was significantly higher than that in normal tissue and low-grade glioma;PPIB was significantly cor-related with glioma grade,IDH wild type,and 1p/19q non-co-deletion(P＜0.001).The overall survival and progression-free inter-val of patients with high expression of PPIB were lower than those of patients with low expression of PPIB.In addition to the elevated ex-pression of PPIB in the pathological tissues of high-grade glioma,the high-expression area of PPIB was accompanied by a large number of tumor-associated macrophage infiltration.Conclusion Compared with low-grade gliomas,the expression levels of PPIB were higher in high-grade gliomas,and there were significant tumor-associated macrophage infiltration in PPIB-expressing areas.It is suggested that PPIB may serve as an independent prognostic factor for patients with glioma,providing reference for the prognosis of patients judg-ment.

Objective To construct adenoviral Ad-pki-67-E1 A-GFP containing the promoter of the ki-67gene to achieve replication specifically in ki-67-positive glioma cells.Methods The promoter sequence of the ki-67gene was cloned into the pGL3-basic vector using molecular biology methods.The ki-67 promoter activity was detected by the dual luciferase reporter gene as-say.The ki-67 promoter was constructed into a shuttle plasmid and co-transfected with a helper plasmid in 293 T cells to recombinant adenovirus Ad-pki-67-E1A-GFP.The Ad-pki-67-E1A-GFP was added to glioma cells,and the expression of GFP was ob-served by fluorescence microscopy.Meanwhile,the expression of ki-67gene,the expression of E1A gene,which was essential for adeno-virus replication,and the number of virus copies were detected by real-time fluorescence quantitative polymerase chain reaction(PCR).Results The cloned ki-67sequence was able to activate reporter gene expression in glioma cells;enzymatic digestion and sequencing demonstrated that the ki-67 promoter was constructed into a shuttle plasmid and recombined to obtain the adenovirus Ad-pki-67-E1A-GFP.Ad-pki-67-E1A-GFP could infect glioma cells,and the expression of E1A and the number of virus copies were posi-tively correlated with the expression of ki-67 in the cells.Conclusion The ki-67 promoter-modified adenovirus replicated in glioma cells,providing a basis for further modification for gene therapy of malignant gliomas.

Objective To analyze the influence of shaping on the bending strength of bone plates and the influence of different locking nail distributions on plate force to provide biomechanical references for shaping plates and selecting different locking nail distributions.Methods Finite element simulation analysis of the four-point bending strength of a plate was performed according to the YY/T 0342-2020 standard.Theoretical analysis and finite element simulation method were used to analyze the force on prosthesis models with different lock-nail distributions.Results At 30° bending,the 3.7 mm-thick plate had 28%higher equivalent plastic strain than the 2.7 mm-thick plate.The 3.7 and 2.7 mm-thick plates had ultimate bending angles of 55° and 67°,respectively.The crease had little impact on the plate stress.The four-point bending strength and equivalent bending stiffness of the unshapeed structure were 2.64 N·m and 1.12 N·m2,respectively.The four-point bending strength and equivalent bending stiffness with the crease were 2.63 N·m and 1.10 N·m2,respectively.After forward and backward bending,the four-point bending strength of the plate decreased from 2.64 to 2.45 N·m by approximately 7.72%,and the equivalent bending stiffness decreased from 1.12 to 0.98 N·m2 by approximately 12%.The impact was obvious.After implantation of tamponade screws,the four-point bending strength of the single-hole plate improved significantly from 2.64 to 3.15 N·m,by approximately 19.32%and the equivalent bending stiffness increased from 1.12 to 1.14 N·m2,by approximately 2.1%.At least two locking holes were reserved on both sides of the fracture line.Not inserting the locking screw reduced the stress by approximately 50%compared with the full insertion of the locking screw.During 15-week postoperative walking without bone callus formation,the material stress of TC4 reached 852.7 MPa and yielding occurred.Conclusions In a clinical scenario where larger shaping is required,it is not suitable for plates with larger thicknesses and plate fractures are more likely to occur after large-thickness shaping.This can guide the clinical selection of plates with appropriate thickness based on the shaping angle,and tamponade screws can be implanted in extreme cases.Fixing locking screws clinically is recommended;however,a method of fixing the locking screws with full screws is not recommended.The biomechanical effect is best when two locking holes at both ends of the fracture line are maintained without fixing the locking screws.

Ocular diseases pose a significant challenge to global health. The field of metabolomics, which involves the systematic identification and quantification of metabolites within a biological system, has emerged as a promising research approach for unraveling disease mechanisms and discovering novel biomarkers. Through its application, metabolomics has yielded valuable knowledge pertaining to the initiation and advancement of various ocular diseases. This review presents an overview of metabolomics and examines recent research progess in four ocular diseases, specifically diabetic retinopathy, age-related macular degeneration, glaucoma, and dry eye, summarizing potential biomarkers and metabolic pathways associated with these diseases. Additionally, this review offers insights into the future prospects of utilizing metabolomics for the management and treatment of ocular diseases.

Objective:To assess the effects of nutritional interventions combined with Traditional Chinese Med-icine(TCM)physical dialectics on the development of gestational diabetes mellitus(GDM),dietary status during pregnancy,and maternal and infant outcomes in high-risk pregnant women in early pregnancy.Methods:298 high-risk pregnant women with GDM in early pregnancy(gestational week≤14 weeks)registered in the Obstet-rics Department of Urumqi Maternal and Child Health Hospital from 1st December 2022 to 30th March 2023 were selected as the study subjects and randomly divided into the intervention group(149 cases)and the control group(149 cases).During 14 to 23+6 weeks of pregnancy,TCM constitution nutritional intervention was carried out for pregnant women in the intervention group,and routine guidance and healthy dietary education was carried out in the control group.The incidence of GDM in the two groups was compared at 24-28 weeks of pregnancy,and the relationship between early pregnancy nutritional intervention combined with TCM constitution and the risk of GDM was analysed in subgroups using logistic regression and likelihood ratio test.The dietary situation,biochemical in-dexes and delivery outcomes after the intervention were compared at 32-36 weeks of pregnancy.Results:①The incidence of GDM in the intervention group was significantly lower than that in the control group(14.09％vs.23.49％,P＜0.05).The effect of the TCM constitution based nutritional intervention on the risk probability of GDM was statistically significant only among pregnant women with different ranges of gestational weight gain(GWG)(P=0.018).Among them,pregnant women with GWG lower than the recommended range had a reduced risk of GDM after intervention(OR 0.27,95％Cl 0.10-0.68,P=0.008).② After intervention,the evaluation index of di-etary balance index of pregnant women in the intervention group was better than that of the control group(P＜0.05),and the intake of cereals and potatoes,vegetables,and water of pregnant women in late pregnancy in the intervention group was higher than that of the control group(P＜0.05).③The levels of triglycerides,total choles-terol,low-density lipoprotein,glycated haemoglobin,uric acid and creatinine of pregnant women in the intervention group were lower than those of the control group in late pregnancy(P＜0.05).GWG,gestational age at delivery,the rate of low-birth-weight,and the neonatal 1-minute Apgar scores were all better than those of the control group(P＜0.05.Conclusions:Nutritional interventions in early pregnancy combined with TCM constitution can sig-nificantly reduce the incidence of GDM in high-risk pregnant women and the chances of low-birth-weight babies.Obstetrics outpatient clinics can actively develop extensive collaboration with TCM and clinical nutrition depart-ments to reduce adverse pregnancy outcomes for both mother and fetus.

ObjectiveTo support intelligent clinical decision-making in traditional Chinese medicine（TCM）， this study utilized ontology and knowledge graph construction techniques to achieve the IT application of clinical practice guidelines. MethodBased on the principles of findability， accessibility， interoperability， and reusability （FAIR principles）， this study employed ontology techniques to construct an ontology for TCM clinical practice guidelines and built a knowledge graph using coronary heart disease as an example. Based on the Checklist for Reporting Practice Guidelines in Traditional Chinese Medicine and Recommendation Grading in TCM Clinical Guidelines/Consensus （T/CAS 530—2021），the ontology of TCM clinical practice guidelines was constructed using the seven-step ontology construction method. On this basis，the TCM diagnosis and treatment data from the Guidelines for the Diagnosis and Treatment of Stable Angina Pectoris in Coronary Heart Disease were stored in Neo4j in the form of triples through knowledge extraction，integration，and storage. ResultThe information in the clinical practice guidelines was divided into three categories： onset and prevention information， diagnosis information， and treatment information， and the TCM clinical practice guideline ontology was constructed. A total of 27 concepts related to TCM clinical diagnosis and treatment and 14 data attributes were obtained， and 12 conceptual relationships including hierarchical relationships and object attributes were established. By taking coronary heart disease as an example and the TCM clinical practice guideline ontology as the model layer， the knowledge map of TCM diagnosis and treatment guidelines for stable angina pectoris in coronary heart disease with 276 nodes and 336 relationships was constructed， realizing the visual display and query of the guideline content. ConclusionThe ontology of TCM clinical practice guidelines and the knowledge graph of stable angina pectoris in coronary heart disease constructed by combining the seven-step ontology construction method and Neo4j graph database technology are efficient and flexible，providing an intelligent TCM diagnosis and treatment scheme and promoting the standardization and objectification of TCM diagnosis and treatment.

Objective:To assess the effects of nutritional interventions combined with Traditional Chinese Med-icine(TCM)physical dialectics on the development of gestational diabetes mellitus(GDM),dietary status during pregnancy,and maternal and infant outcomes in high-risk pregnant women in early pregnancy.Methods:298 high-risk pregnant women with GDM in early pregnancy(gestational week≤14 weeks)registered in the Obstet-rics Department of Urumqi Maternal and Child Health Hospital from 1st December 2022 to 30th March 2023 were selected as the study subjects and randomly divided into the intervention group(149 cases)and the control group(149 cases).During 14 to 23+6 weeks of pregnancy,TCM constitution nutritional intervention was carried out for pregnant women in the intervention group,and routine guidance and healthy dietary education was carried out in the control group.The incidence of GDM in the two groups was compared at 24-28 weeks of pregnancy,and the relationship between early pregnancy nutritional intervention combined with TCM constitution and the risk of GDM was analysed in subgroups using logistic regression and likelihood ratio test.The dietary situation,biochemical in-dexes and delivery outcomes after the intervention were compared at 32-36 weeks of pregnancy.Results:①The incidence of GDM in the intervention group was significantly lower than that in the control group(14.09％vs.23.49％,P＜0.05).The effect of the TCM constitution based nutritional intervention on the risk probability of GDM was statistically significant only among pregnant women with different ranges of gestational weight gain(GWG)(P=0.018).Among them,pregnant women with GWG lower than the recommended range had a reduced risk of GDM after intervention(OR 0.27,95％Cl 0.10-0.68,P=0.008).② After intervention,the evaluation index of di-etary balance index of pregnant women in the intervention group was better than that of the control group(P＜0.05),and the intake of cereals and potatoes,vegetables,and water of pregnant women in late pregnancy in the intervention group was higher than that of the control group(P＜0.05).③The levels of triglycerides,total choles-terol,low-density lipoprotein,glycated haemoglobin,uric acid and creatinine of pregnant women in the intervention group were lower than those of the control group in late pregnancy(P＜0.05).GWG,gestational age at delivery,the rate of low-birth-weight,and the neonatal 1-minute Apgar scores were all better than those of the control group(P＜0.05.Conclusions:Nutritional interventions in early pregnancy combined with TCM constitution can sig-nificantly reduce the incidence of GDM in high-risk pregnant women and the chances of low-birth-weight babies.Obstetrics outpatient clinics can actively develop extensive collaboration with TCM and clinical nutrition depart-ments to reduce adverse pregnancy outcomes for both mother and fetus.

Objective:To assess the effects of nutritional interventions combined with Traditional Chinese Med-icine(TCM)physical dialectics on the development of gestational diabetes mellitus(GDM),dietary status during pregnancy,and maternal and infant outcomes in high-risk pregnant women in early pregnancy.Methods:298 high-risk pregnant women with GDM in early pregnancy(gestational week≤14 weeks)registered in the Obstet-rics Department of Urumqi Maternal and Child Health Hospital from 1st December 2022 to 30th March 2023 were selected as the study subjects and randomly divided into the intervention group(149 cases)and the control group(149 cases).During 14 to 23+6 weeks of pregnancy,TCM constitution nutritional intervention was carried out for pregnant women in the intervention group,and routine guidance and healthy dietary education was carried out in the control group.The incidence of GDM in the two groups was compared at 24-28 weeks of pregnancy,and the relationship between early pregnancy nutritional intervention combined with TCM constitution and the risk of GDM was analysed in subgroups using logistic regression and likelihood ratio test.The dietary situation,biochemical in-dexes and delivery outcomes after the intervention were compared at 32-36 weeks of pregnancy.Results:①The incidence of GDM in the intervention group was significantly lower than that in the control group(14.09％vs.23.49％,P＜0.05).The effect of the TCM constitution based nutritional intervention on the risk probability of GDM was statistically significant only among pregnant women with different ranges of gestational weight gain(GWG)(P=0.018).Among them,pregnant women with GWG lower than the recommended range had a reduced risk of GDM after intervention(OR 0.27,95％Cl 0.10-0.68,P=0.008).② After intervention,the evaluation index of di-etary balance index of pregnant women in the intervention group was better than that of the control group(P＜0.05),and the intake of cereals and potatoes,vegetables,and water of pregnant women in late pregnancy in the intervention group was higher than that of the control group(P＜0.05).③The levels of triglycerides,total choles-terol,low-density lipoprotein,glycated haemoglobin,uric acid and creatinine of pregnant women in the intervention group were lower than those of the control group in late pregnancy(P＜0.05).GWG,gestational age at delivery,the rate of low-birth-weight,and the neonatal 1-minute Apgar scores were all better than those of the control group(P＜0.05.Conclusions:Nutritional interventions in early pregnancy combined with TCM constitution can sig-nificantly reduce the incidence of GDM in high-risk pregnant women and the chances of low-birth-weight babies.Obstetrics outpatient clinics can actively develop extensive collaboration with TCM and clinical nutrition depart-ments to reduce adverse pregnancy outcomes for both mother and fetus.