De-Qi Jiang

Background: Paroxetine therapy has been used for treatment of patients with depression and Parkinson’s disease (dPD) in many clinical studies, but, the effects of paroxetine in dPD patients are not completely understood. The aim of this study was to systematically evaluate the effects of paroxetine therapy on depressive symptom and motor function in the treatment of dPD, in order to confer a reference for clinical practice. Methods: Randomized controlled trials (RCTs) of paroxetine for dPD published up to October, 2022 were retrieved. Standardised mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was measured with the I ² test. The outcomes of interest were as follows: the efficacy, Hamilton depression rating scale score, unified Parkinson’s disease rating scale score, Hamilton anxiety rating scale score or adverse events. Results: Thirty-four RCTs with 2819 participants were included. Compared with control group, the pooled effects of paroxetine therapy on depression were (22 trials; OR 3.62, 95% CI 2.63 to 4.98, P < .00001) for antidepressant response (25 trials; SMD -2.14, 95% CI -2.73 to -1.56, P < .00001) for Hamilton depression rating scale score, the pooled effects of paroxetine therapy on motor function were (10 trials; OR 4.63, 95% CI 3.15 to 6.79, P < .00001) for anti-PD efficacy (18 trials; SMD -2.02, 95% CI -2.48 to -1.55, P < .00001) for total unified Parkinson’s disease rating scale score. The Hamilton anxiety rating scale score showed significant decrease in the paroxetine treatment group compared to control group (10 trials; SMD -1.93, 95% CI -2.65 to -1.22, P < .00001). In addition, paroxetine therapy reduced the number of any adverse events obviously in dPD patients (twenty trials; OR 0.42, 95% CI 0.31 to 0.57, P < .00001). Conclusions: Paroxetine therapy has clinical benefits for improvement of depressive symptom and motor function in dPD patients, moreover, it is of high drug safety. Further well-designed, multi-center RCTs needed to identify these findings.

The mitochondrial protein sirtuin 3 (SIRT3) can counteract cell damage caused by oxidative stress and inflammation, and contribute to cell survival primarily by improving mitochondrial function. However, the effects of SIRT3 in dopaminergic neuronal cells (DACs) remain unclear. In our previous studies, microglia activation‑associated cytotoxicity was observed to promote the apoptosis of DACs, along with the decrease of SIRT3 expression. The aim of the present study was to explore the potential neuroprotective effect of SIRT3 expression against dopaminergic neuron injury caused by microglia activation, and clarify its possible mechanisms. SIRT3 overexpression in DACs reduced the production of intracellular reactive oxygen species (ROS), cell apoptosis rate, mitochondrial membrane potential (ΔΨm) depolarization, opening of mitochondrial permeability transition pore (mPTP) and cyclophilin D (CypD) protein level, and promoted cell cycle progression. However, SIRT3 siRNA‑mediated knockdown further aggravated microglia activation‑mediated cytotoxicity, including ROS accumulation, increased cell apoptosis and mPTP opening, elevated the CypD level, enhanced mitochondrial ΔΨm depolarization, concomitant to cell cycle arrest at G₀/G₁ phase. The mechanisms of SIRT3 mitigated microglia activation‑induced DAC dysfunction, which included decreased mPTP opening and Bax/Bcl‑2 ratio, inhibition of mitochondrial cytochrome c release to the cytoplasm, reduced caspase‑3/9 activity, increased LC3II/LC3I and beclin‑1 protein expression levels, and decreased nucleotide‑binding oligomerization domain, leucine rich repeat and pyrin domain‑containing protein 3 (NLRP3), caspase‑1, IL‑1β and IL‑18 protein expression. In conclusion, these results indicated that SIRT3 expression attenuated cell damage caused by microglia activation through the mitochondrial apoptosis pathway in DACs. The mitophagy‑NLRP3 inflammasome pathway may also be associated with this neuroprotection. These findings may provide new intervention targets for the survival of dopaminergic neurons and the prevention and treatment of Parkinson's disease.

Background: Pramipexole (P) or levodopa (L) treatment has been suggested as a therapeutic method for Parkinson disease (PD) in many clinical studies. Nonetheless, the combined effects of 2 drugs for PD patients are not completely understood. The aim of this research was to evaluate the clinical efficacy and safety of P plus L (P+L) combination therapy in the treatment of PD compared to that of L monotherapy, in order to confer a reference for clinical practice. Methods: Randomized controlled trials (RCTs) of P+L for PD published up to April, 2020 were retrieved. Standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was measured with the I ² test. Sensitivity analysis was also carried out. The outcomes of interest were as follows: the efficacy, unified Parkinson disease rating scale (UPDRS) scores, Hamilton depression rating scale score or adverse events. Results: Twenty-four RCTs with 2171 participants were included. Clinical efficacy of P+L combination therapy was significantly better than L monotherapy (9 trials; OR 4.29, 95% CI 2.78 to 6.64, P < .00001). Compared with L monotherapy, the pooled effects of P+L combination therapy on UPDRS score were (22 trials; SMD −1.31, 95% CI −1.57 to −1.04, P < .00001) for motor UPDRS score, (16 trials; SMD −1.26, 95% CI −1.49 to −1.03, P < .00001) for activities of daily living UPDRS score, (12 trials; SMD −1.02, 95% CI −1.27 to −0.77, P < .00001) for mental UPDRS score, (10 trials; SMD −1.54, 95% CI −1.93 to −1.15, P < .00001) for complication UPDRS score. The Hamilton depression rating scale score showed significant decrease in the P+L combination therapy compared to L monotherapy (12 trials; SMD −1.56, 95% CI −1.90 to −1.22, P < .00001). In contrast to L monotherapy, P+L combination therapy reduced the number of any adverse events obviously in PD patients (16 trials; OR 0.36, 95% CI 0.27 to 0.50, P < .00001). Conclusions: P+L combination therapy is superior to L monotherapy for improvement of clinical symptoms in PD patients. Moreover, the safety profile of P+L combination therapy is better than that of L monotherapy. Further well-designed, multicenter RCTs needed to identify these findings.

To explore the expressions of calculus-related functional proteins in the ureteral calculus-adhered polyp tissues and investigate the role of these proteins in the formation of adhesions between the calculus and polyp. Patients with ureteral calculi and polyps who underwent ureteroscopic lithotripsy for the excision of polyps between January 2019 and June 2019 were enrolled. Polyps obtained from each patient were divided into 2 groups using a matched pairs design: observation group (polyps adhered to calculus) and control group (polyps not adhered to calculus). Histopathological examination of polyps was performed using hematoxylin and eosin staining. Polyp tissues were immunohistochemically stained to assess the expressions of calculus-related functional proteins, that is, annexin A1, calcium-binding protein S100A9 (S100A9), uromodulin, and osteopontin. Furthermore, quantitative analysis was performed using the H-score of tissue staining; Pearson correlation analysis was performed for proteins with high expression. Overall, 40 polyp specimens were collected from 20 patients with ureteral calculi combined with polyps (observation group, 20 specimens; control group, 20 specimens). Hematoxylin and eosin staining revealed obvious epithelial cell proliferation in polyps of both groups; crystals were observed in the epithelial cells of the polyp tissue in the observation group. The expression levels of annexin A1 and S100A9 in the observation group were significantly greater than those in the control group (P < .05). However, no obvious expression of osteopontin or uromodulin was observed in the polyp tissues of both groups. There was a strong correlation between the increased expressions of annexin A1 and S100A9 in the observation group (R = 0.741, P = .022). We documented increased expressions of annexin A1 and S100A9 in the ureteral calculus-adhered polyp tissues. Annexin A1 and S100A9 may play an essential role in the adhesion of calculus and polyp and the growth of calculi.

The purpose of this research was to evaluate the clinical efficacy and safety of pramipexole plus levodopa/benserazide (P+LB) combination therapy in the treatment of Parkinson’s disease (PD) compared to that of LB monotherapy, in order to confer a reference for clinical practice. Randomized controlled trials (RCTs) of P+LB for PD published up to April 2020 were retrieved. Heterogeneity and sensitivity analysis were executed. Twenty-nine RCTs with 3017 participants were included. Clinical efficacy of P+LB combination therapy was significantly better than LB monotherapy (RR 1.27, 95% CI 1.22 to 1.32, PPPP=0.0001) for mental UPDRS score, and (SMD −1.60, 95% CI −2.06 to −1.15, PPP<0.00001). In conclusion, P+LB combination therapy is superior to LB monotherapy for improvement of clinical symptoms in PD patients. Moreover, the safety profile of P+LB combination therapy is better than that of LB monotherapy. Further well-designed, multi-center RCTs needed to identify these findings.

Background: It has been reported that polymorphisms of transferrin (TF) G258A and transferrin receptor (TFR) A82G might be associated with susceptibility to Parkinson disease (PD). Objective: Owing to limitation of sample size and inconclusive results, we conducted a meta-analysis to clarify the association. Methods: By searching PubMed, Embase, Chinese National Knowledge Infrastructure, China Biological Medicine Database, and Wanfang Databases, the published articles about studies of the association of the TF G258A, TFR A82G gene polymorphisms with the risk of PD were collected. Q-statistics and I ² statistics were calculated to examine heterogeneity and summary odds ratios (ORs) and 95% confidence intervals (95%CI) were evaluated the association. Results: Five studies assessed the relationship between TF G258A and risk of PD. A significant increased protective of A allele and AA genotype was observed in allele model and recessive model (the allele model A vs G: OR = 0.54, 95%CI 0.40–0.72, P < .001; the recessive model AA vs GA + GG: OR = 0.32, 95%CI 0.20–0.52, P < .001). The remaining models of the TF G258A genotype showed no significant association with PD risk, while the protective tendency were increased (the heterozygote model GA vs GG: OR = 0.93, 95%CI 0.61–1.43, P = .75; the homozygous model AA vs GG: OR = 0.47, 95%CI 0.21–1.04, P = .06; the dominant model GA + AA vs GG: OR = 0.75, 95%CI 0.50–1.11, P = .15). There was also a lack of association between TFR A82G polymorphism and PD (the allele model G vs A: OR = 0.92, 95%CI 0.75–1.13, P = .43; the heterozygote model AG vs AA: OR = 1.17, 95%CI 0.79–1.71, P = .43; the homozygous model GG vs AA: OR = 0.91, 95%CI 0.60–139, P = .66; the dominant model AG + GG vs AA: OR = 1.05, 95%CI 0.73–1.49, P = .81; the recessive model GG vs AG +AA: OR = 0.80, 95%CI 0.59–1.09, P = .16). Conclusion: Our study suggests that TF G258A polymorphism may be associated with PD, while TFR A82G polymorphism may not contribute to PD based on the current evidence.

Objective The aim of this report was to systematically evaluate the efficacy and safety of rasagiline (R) plus levodopa (l) (R + l) for the treatment of Parkinson’s disease (PD) compared with that of l monotherapy, in order to provide a reference resource for rational drug use. Methods Randomized controlled trials (RCTs) of R + l for PD published up to September 2018 were searched. Sensitivity analyses were also performed. Results Fourteen RCTs with 2531 participants were included. Compared with l monotherapy, the pooled effects of R + l combination therapy on unified Parkinson’s disease rating scale (UPDRS) score were (SMD − 0.50, 95% CI − 0.70 to − 0.30, P < 0.00001) for UPDRS motor score, (SMD − 0.59, 95% CI − 0.79 to − 0.39, P < 0.00001) for UPDRS activities of daily living (ADL) score, (SMD − 0.65, 95% CI − 0.81 to − 0.49, P < 0.00001) for UPDRS total score. R + l combination therapy was better than l monotherapy in reducing daily off-time (SMD − 1.15, 95% CI − 2.13 to − 0.17, P = 0.02), but there was a statistically nonsignificant result in daily on-time increase (SMD 1.39, 95% CI − 0.69 to 3.48, P = 0.19). There were no statistical differences in number of adverse events (OR 1.33, 95% CI 0.97 to 1.82, P = 0.07) and number of dropout (OR 0.88, 95% CI 0.65 to 1.19, P = 0.39) between R + l combination therapy and l monotherapy. Conclusions R + l combination therapy was superior to l monotherapy for improvement of UPDRS scores and off-time in PD patients. Moreover, R + l combination therapy and l monotherapy were similar in terms of safety and tolerability.

The -2518A/G polymorphism in monocyte chemotactic protein-1 (MCP-1) has been extensively investigated for association with Alzheimer’s disease (AD); however, the results from different studies are inconsistent. The aim of this study was to draw an accurate conclusion of the association. All eligible case–control studies were searched in PubMed, Embase, Chinese National Knowledge Infrastructure, China Biological Medicine Databases, and Wanfang Databases. Eight case–control studies with a total of 2370 cases and 2413 controls were eligible to be included in this meta-analysis. The association was evaluated by calculating the odds ratios (ORs) with the corresponding 95% confidence intervals (CIs). Overall, there was no significant association between MCP-1-2518A/G polymorphism and AD risk in all genetic models (the allele model G vs. A: OR = 1.15, 95% CI 0.92–1.45, p = 0.22; the co-dominant model GG vs. AA: OR = 1.38, 95% CI 0.80–2.36, p = 0.25; the dominant model AG + GG vs. AA: OR = 1.14, 95% CI 0.89–1.46, p = 0.31; the recessive model GG vs. AG + AA: OR = 1.35, 95% CI 0.87–2.09, p = 0.18). In subgroup analysis by ethnicity, a significant difference was not detected in both Caucasians and Asians. In allele model (G vs. A), the required sample size of 31858 was calculated by applying trial sequential analysis. Cumulative z curve is always below the trial sequential monitoring boundary and is nominally statistically significant (Z = 1.96). A consistent result was obtained in other genetic models. In summary, the present meta-analysis suggests that MCP-1-2518A/G polymorphism may not be associated with genetic susceptibility of AD in general population, but the association remains indeterminate due to the insufficient evidence.

The aim of this systematic review was to evaluate the efficacy and safety of liraglutide versus sitagliptin both in combination with metformin in patients with type 2 diabetes and provide reference basis for rational use of clinical drugs. Several databases were searched, including Web of science, PubMed, Cochrane library, CNKI, and Wanfang database. Only randomized controlled trials (RCTs) of liraglutide versus sitagliptin both in combination with metformin up to 31 August 2016 were included. Data were extracted independently by 2 reviewers, and a fixed or random effects model were used to analyze outcomes that were expressed as odds ratio (OR) or mean difference (MD) and 95% confidence intervals (95% CIs) for different situations. Five RCTs involving 1440 participants were included. Compared with sitagliptin combination with metformin group, participants’ treatment with 1.2 mg and 1.8 mg liraglutide with metformin could significantly lower the level of glycosylated hemoglobin (HbA1c) (P < .00001, MD = −0.35, 95% CI −0.51 to −0.20). Moreover, patients with 1.8 mg liraglutide group had significant body weight loss (P < .00001, MD = −1.12, 95% CI −1.54 to −0.70). However, there were no obvious differences in cutting down the systolic blood pressure and diastolic blood pressure between liraglutide-metformin and sitagliptin-metformin groups. The incidence of gastrointestinal problems was significantly higher than sitagliptin with metformin groups. The results of this meta-analysis indicated that Liraglutide added on to metformin therapy could significantly lower the level of HbA1c and increase body weight loss. Meanwhile, the adverse reactions such as gastrointestinal problems were common in the liraglutide treatment group. Thus, this will provide an important reference for the treatment of patients with type 2 diabetes.