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 alteration of blood routine parameters,blood gas analysis profile,coagulation function,and inflammatory factors during exposure to high-altitude hypoxic environments.Methods Rats were raised in a hypobaric oxygen chamber to simulate the altitude of 5 500 meters.The animals were divided into groups with exposure duration of 0(control),1,3,5,7,14,and 28 days.Arterial blood gas was measured using a blood gas analyzer.The routine blood test was performed by an automatic five-differential animal hematology analyzer.The coagulation function was measured by a fully automatic coagulation analyzer.The level of plasma D-dimer(DD),erythropoietin(EPO),interleukin-10(IL-10),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and C-reactive protein(CRP)was detected by ELISA method.The protein expression of IL-10,IL-6,and TNF-α in lung tissues of the animals was detected by Western blot.Results As compare to control group,the arterial partial pressure of ox-ygen(PaO2)decreased at different durations of hypoxia exposure.The PaO2 in the group exposed to hypoxia for 7 d was the lowest(P＜0.05).The red blood cell count(RBC),hemoglobin(HGB),hematocrit(HCT),mean cor-puscular volume(MCV),mean corpuscular hemoglobin concentration(MCHC)and mean platelet volume(MPV)were all higher than control group(P＜0.05).Erythropoietin(EPO),prothrombin time(PT),activated partial thromboplastin time(APTT),thrombin time(TT),fibrinogen(FIB)and D-dimer(DD)all gradually increased(P＜0.05).The white blood cell count(WBC)and platelet count(PLT),as well as the plasma inflammatory fac-tors including interleukin-10(IL-10),interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),C-reactive protein(CRP),and the expression of inflammatory factors in the lung tissue including IL-10,IL-6 and TNF-α pro-teins all showed a curve of increasing at beginning and then followed by a slow decrease with the prolongation of the hypoxia time(P＜0.05).Conclusions In high-altitude hypoxic environment,the blood circulation undergoes dy-namic evolution of functional remodeling with higher risk of inflammatory response.As the hypoxia time prolongs,the animals adapt the environment and the level of inflammatory cytokines gradually decline but remains at a level which is still higher than that of control animals.

Objective To understand the willingness to engage in the combine medical care with old-age care institutions of medical students in vocational colleges and analyze their influencing factors.Methods By convenient sampling method,1 266 medical students from 3 vocational colleges in Hunan Province were select-ed as the research objects,and their occupational cognition and occupational willingness were investigated and analyzed.Through objective sampling,20 medical students who were not willing to work in medical institu-tions were selected for semi-structured interviews.Results 62.1%of medical students intend to work in med-ical institutions after graduation;The results of multi-factor analysis showed that the experience of caring for the elderly,understanding of the nursing institution,participating in the volunteer service of the nursing insti-tution,and cognition score of the combination of medical care and nursing were the influencing factors of med-ical students'career intention(P＜0.05).The qualitative interview found that professional identity,job abili-ty,salary,social security and promotion were the main influencing factors.Conclusion Medical students in medical nursing institutions do not have strong willingness,so they should improve their professional cogni-tion of old-age service,enhance their professional identity and post competency,fully implement salary,social security and professional title promotion,attract more medical students to engage in the combined service in-dustry,and promote the combined development of medical care.

Objective:To evaluate the clinical efficacy of acupuncture combined with low-frequency repetitive transcranial magnetic stimulation (rTMS) in the treatment of heart and liver fire hyperactivity syndrome in children with tic disorder; To explore its effects on the levels of serum neurotransmitters in children.Methods:A randomized controlled trial study was conducted. A total of 86 children with heart and liver fire hyperactivity syndrome of tic disorder in our hospital from March 2022 to March 2024 were selected as the observation objects and divided into 2 groups using the random number table method, with 43 cases in each group. The control group was treated with rTMS, while the observation group was treated with combined acupuncture on the basis of the control group. Both groups were treated continuously for 8 weeks. The TCM syndrome scores were conducted before and after the treatment respectively. The Yale Comprehensive Tic Severity Scale (YGTSS) was used to evaluate the severity of clinical symptoms, and the levels of serum γ -aminobutyric acid (γ-GABA), dopamine (DA), and 5-hydroxytryptamine (5-HT) were detected by ELISA. The adverse reactions during the treatment period were recorded and the clinical efficacy was evaluated.Results:The total effective rate was 90.70% (39/43) in the observation group and 72.09% (31/43) in the control group, with statistical significance ( χ2=4.91, P=0.027). After treatment, the scores of convulsion and peristalsis, flushed face and ears, irritability and anger, and red tongue with yellow coating in the observation group were lower than those in the control group ( t values were 3.80, 2.94, 3.26, and 4.22 respectively, P<0.01), and the scores of vocal tics, motor tics and the total score were lower than those in the control group (t values were 7.97, 5.23, and 6.44 respectively, P<0.01). After treatment, the level of γ-GABA in the observation group [(9.72±2.04) μg/L vs. (8.13±1.87) μg/L, t=3.77] was higher than that of the control group ( P<0.01), and DA [(8.98±1.94) μg/L vs. (12.10±2.27) μg/L, t=6.85], levels of 5-HT [(15.20±3.87) μg/L vs. (19.93±3.97) μg/L, t=5.59] were lower than those in the control group ( P<0.01). During the treatment period, the incidence of adverse reactions was 11.63% (5/43) in the observation group and 9.30% (4/43) in the control group, without statistical significance ( χ2=0.12, P=0.725). Conclusion:Acupuncture combined with rTMS can alleviate the tic symptoms of children of tic disorder with heart and liver fire hyperactivity syndrome, improve the neurotransmitter levels and main TCM syndromes of the children, enhance the clinical efficacy and have good treatment safety.

Objective:To distinguish Hedyotis diffusa Willd. and its common countrerfeit, Hedyotis corymbosa. and Hedyotis tenelliflora. by analyzing and comparing their macroscopical identification, microscopic character and HPLC fingerprints. Methods:The features of macroscopical identification, microscopic character including cross-sections of stem, leaf, fruit and seed, and herbal powders were observed in the three samples by traditional methods. The difference of chromatographic peaks among the three samples were also analyzed by HPLC methods.Results:The stems of Hedyotis diffusa Willd. were cylindrical, and the capsules were solitary or double born in the leaf axils, oblate, 2-3 mm in diameter, with a long petiole; the Hedyotis corymbosa. and Hedyotis tenelliflora. were tetragonal, and the Hedyotis corymbosa. was 2-5 capsules born in leaf axils in corymbose inflorescences, globular, 1-1.5 mm in diameter, with a slender petiole; the Hedyotis tenelliflora. were 1-3 capsules clustered in the leaf axils, ovoid with longitudinal ribs around the margin, about 1.5 mm in diameter, without the long petiole, about 1.5 mm in diameter, sessile, the edge of the leaf drying revolute long needle-like. Under the identification, the cross section of the Hedyotis diffusa Willd. stem was almost round, the middle vein of the leaves was protrusion below, the inner pericarp fiber layer consisted of two layers of fiber cells, the surface of the seed coat cells was polygon, and the wall was densely covered with small reddish brown or yellow-brown warty spots. The cross section of the Hedyotis corymbosa. stem was quadrilateral, the surface of the seed coat cell was polygon, the wall was wavy and curved, and there was no warty point on the wall. The middle veins of the Hedyotis tenelliflora. were slightly sunken in the upper part, but not protruding in the lower part; the endocarp fiber layer consisted of 8 to 13 layers of fiber cells. Moreover, the HPLC fingerprint analysis demonstrated substantial dissimilarities in the characteristic peaks of these herbs. Conclusion:The traditional and modern analysis technology show that there are some differences in the characteristics, microscopical cross section, the powder characteristics, which can effectively distinguish the Hedyotis diffusa Willd. and its two local varieties.

Objective:To investigate the thyroid function status and levothyroxine ( L-T 4) replacement therapy strategy in pregnant women after 131I treatment of hyperthyroidism. Methods:From January 2005 to December 2019, 88 patients (age: (27.3±3.7) years) who received 131I treatment in Nanjing Drum Tower Hospital were retrospectively analyzed. They became pregnant at least half a year after 131I treatment with normal thyroid function and delivered successfully. Thyroid stimulating hormone (TSH), free triiodothyronine (FT 3) and free thyroxine (FT 4) were respectively detected at 1-3 months before pregnancy, 4-7, 8-12, 13-22, 23-28, ≥29 weeks of pregnancy, and 6 weeks, 3 months, 6 months of postpartum. According to the 2011 American Thyroid Association guidelines, L-T 4 replacement therapy was performed to maintain normal thyroid function. Repeated measures analysis of variance and the least significant difference t test were used to analyze data. Results:There were significant differences in TSH, FT 3, FT 4 and L-T 4 among different time periods before pregnancy, pregnancy and postpartum ( F values: 5.94, 3.32, 3.49, 9.63, all P<0.05). In order to maintain normal thyroid function in each period of pregnancy, the doses of L-T 4 replacement therapy were increased to (82.33±35.06) μg and (100.75±36.77) μg at 4-7, 8-12 weeks of pregnancy compared with the dose ((64.52±34.32) μg) before pregnancy ( t values: 7.33, 10.44, both P<0.001). The doses of L-T 4 were increased slowly after 13 weeks of pregnancy. In the third trimester (≥29 weeks), the dose was 76.69% higher than that before pregnancy. There were significant changes of TSH, FT 3 and FT 4 at 6 weeks of postpartum compared with those in the third trimester (TSH: (1.21±1.08) vs (2.99±1.42) mU/L, FT 3: (5.23±1.07) vs (3.90±0.55) pmol/L, FT 4: (21.29±4.96) vs (15.37±2.29) pmol/L, t values: -2.48, 6.05, 5.88, P values: 0.017, <0.001, <0.001). Compared with that in the third trimester, the dose of L-T 4 was decreased significantly at 6 weeks of postpartum ( t=-6.85, P<0.001), but doses of L-T 4 at 6 weeks, 3 months and 6 months of postpartum were still higher than that before pregnancy ( t values: 4.67-4.71, all P<0.001). Conclusions:TSH, FT 3 and FT 4 should be regularly monitored at 1-3 months before pregnancy, gestation period and 6 weeks of postpartum in pregnant women after 131I treatment of hyperthyroidism. The dose of L-T 4 should be adjust to the serum TSH level as soon as possible.

Hepatic dysregulation of lipid metabolism exacerbates inflammation and enhances the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). STAT3 has been linked to lipid metabolism and inflammation. Jolkinolide B (JB), derived from Euphorbia fischeriana, is known for its pharmacological anti-inflammatory and anti-tumor properties. Therefore, this study investigated whether JB affects MASLD prevention by regulating STAT3 signaling. JB attenuated steatosis and inflammatory responses in palmitic acid (PA)-treated hepatocytes. Additionally, JB treatment reduced the mRNA expression of de-novo lipogenic genes, such as acetyl-CoA carboxylase and stearoyl-CoA desaturase 1. Interestingly, JB-mediated reduction in inflammation and lipogenesis was dependent on STAT3 signaling. JB consistently modulated mitochondrial dysfunction and the mRNA expression of inflammatory cytokines by inhibiting PA-induced JAK/STAT3 activation. This study suggests that JB is a potential therapeutic agent to prevent major stages of MASLD through inhibition of JAK/STAT3 signaling in hepatocytes.

Hepatic dysregulation of lipid metabolism exacerbates inflammation and enhances the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). STAT3 has been linked to lipid metabolism and inflammation. Jolkinolide B (JB), derived from Euphorbia fischeriana, is known for its pharmacological anti-inflammatory and anti-tumor properties. Therefore, this study investigated whether JB affects MASLD prevention by regulating STAT3 signaling. JB attenuated steatosis and inflammatory responses in palmitic acid (PA)-treated hepatocytes. Additionally, JB treatment reduced the mRNA expression of de-novo lipogenic genes, such as acetyl-CoA carboxylase and stearoyl-CoA desaturase 1. Interestingly, JB-mediated reduction in inflammation and lipogenesis was dependent on STAT3 signaling. JB consistently modulated mitochondrial dysfunction and the mRNA expression of inflammatory cytokines by inhibiting PA-induced JAK/STAT3 activation. This study suggests that JB is a potential therapeutic agent to prevent major stages of MASLD through inhibition of JAK/STAT3 signaling in hepatocytes.

Hepatic dysregulation of lipid metabolism exacerbates inflammation and enhances the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). STAT3 has been linked to lipid metabolism and inflammation. Jolkinolide B (JB), derived from Euphorbia fischeriana, is known for its pharmacological anti-inflammatory and anti-tumor properties. Therefore, this study investigated whether JB affects MASLD prevention by regulating STAT3 signaling. JB attenuated steatosis and inflammatory responses in palmitic acid (PA)-treated hepatocytes. Additionally, JB treatment reduced the mRNA expression of de-novo lipogenic genes, such as acetyl-CoA carboxylase and stearoyl-CoA desaturase 1. Interestingly, JB-mediated reduction in inflammation and lipogenesis was dependent on STAT3 signaling. JB consistently modulated mitochondrial dysfunction and the mRNA expression of inflammatory cytokines by inhibiting PA-induced JAK/STAT3 activation. This study suggests that JB is a potential therapeutic agent to prevent major stages of MASLD through inhibition of JAK/STAT3 signaling in hepatocytes.

[Objective] To investigate the pathological characteristics of false-positive lesions of prostate cancer on ⁶⁸Ga-PSMA-11 PET/CT based on the pathology of whole mount specimens, in order to more accurately assess the degree of malignancy within the prostate tissue and avoid overdiagnosis and unnecessary treatment. [Methods] A total of 77 patients who underwent ⁶⁸Ga-PSMA-11 PET/CT before radical prostatectomy in Nanjing Drum Tower Hospital during Jan.2018 and Dec.2022 were retrospectively analyzed.The pathology of whole mount specimens was detected.Two nuclear physicians examined all imaging plates without knowing the pathological results.Two pathological physicians completed all pathological diagnosis without knowing the imaging results.The pathological characteristics of false-positive lesions were determined by matching ⁶⁸Ga-PSMA-11 PET/CT and pathological specimens.To analyze the pathological features of false-positive lesions, true-negative lesions were randomly delineated and defined.The pathological features of false-positive and true-negative lesions were analyzed and compared using Fisher exact test. [Results] After the imaging and pathological sections were matched, 21(16.3%) false-positive lesions were identified.The pathological characteristics of the 21 false-positive lesions were as follows: 16 (76.2%) simple atrophy with cyst formation, 3(14.3%) prostatic nodular hyperplasia, and 2(9.5%) inflammation.The pathological characteristics of 21 true-negative lesions were: 13(61.9%) normal glands, 5(23.8%) prostatic nodular hyperplasia and 3(14.3%) simple atrophy with cyst formation.Fisher exact test showed that the proportion of simple atrophy with cyst formation in the pathological features of false-positive lesions and true-negative lesions was statistically significant (76.2% vs.14.3%, P<0.001). [Conclusion] Simple atrophy with cyst formation may be a characteristic pathological type of the false-positive lesions of prostate cancer on ⁶⁸Ga-PSMA-11 PET/CT.