The efficacy of repetitive transcranial magnetic stimulation for Parkinson disease patients with depression.

Objective: To evaluate the efficacy of repetitive transcranial magnetic stimulation for Parkinson disease (PD) patients with depression.Methods: A meta-analysis was performed using relevant randomized controlled trials (RCTs) from online databases such as PubMed, Embase, Cochrane Online Library, and Clinicaltrials.gov. Studies were selected according to pre-defined inclusion and exclusion criteria, and the quality of the studies was evaluated using the Jadad Scale. All data were pooled by RevMan 5.2 software for meta-analysis.Results: The review covered 528 articles, and 7 articles with Jadad score ≥4 were included in the analysis. The meta-analysis showed that, compared to sham repetitive transcranial magnetic stimulation (sham-rTMS), repetitive transcranial magnetic stimulation (rTMS) over dorsolateral prefrontal cortex (DLPFC) improved depression, but that there was no significant difference in depression improvement between rTMS and selective serotonin reuptake inhibitor (SSRI) treatment. In contrast, rTMS over DLPFC did not improve motor function compared to sham-rTMS or SSRI, and the studies that included neurocognitive measures showed no significant difference between rTMS and sham-rTMS.Conclusion: This meta-analysis provides evidence that rTMS over DLPFC can improve depression similar to SSRI treatment, has no effect on the motor function and cognition of PD patients with depression.

[Discovery and study on potential effect of herbal pair of Uncariae Ramulus cum Uncis-Eucommiae Cortex on pregnancy hypertension based on network pharmacology and molecular docking].

This study aimed to explore the optimal indications and mechanism of Uncariae Ramulus cum Uncis(UR)-Eucommiae Cortex(EC) in lowering blood pressure based on network pharmacology and molecular docking. Chemical constituents were collected and screened by TCMSP database. Swiss Target Prediction platform was used to predict the related targets of the drug. OMIM, TCMIP and GeneCards databases were used to collect hypertension-related genes, and the intersections were taken to obtain potential targets for anti-hypertensive treatment of UR-EC. FunRich software was used to enrich the clinical phenotype and expression site of potential target of lowering blood pressure to analyze and predict the optimal indications of UR-EC. STRING database was used for KEGG pathway enrichment analysis, and Cytoscape 3.7.2 was used to construct the network of "composition-target-pathway". The key targets and their corresponding components in the network were analyzed and obtained, and then molecular docking was applied for preliminary verification. Twenty potential active components of UR and 24 potential active components of EC were respectively collected, and 92 anti-hypertensive potential targets of UR-EC were obtained. According to FunRich enrichment results, the optimal indication of UR-EC was pregnancy hypertension, which involved calcium signaling pathway, HIF-1 signaling pathway, neuroactive ligand receptor interaction, renin vascular tightening, VEGF signaling pathway, etc. In addition, AKT1, NOS2, ADRB2, F2, NOS3, SCN5 A, HTR2 A and JAK2 were considered as the key targets in the network. The molecular docking results showed that the screened potential active components had high binding activity with the key targets. This study preliminarily revealed that UR-EC may have therapeutic effects on pregnancy hypertension in terms of sedation, anti-hypertension, anti-inflammatory, anti-oxidation, improvement of vascular endothelial function and so on.

Mesencephalic astrocyte-derived neurotrophic factor and its role in nervous system disease.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a member of the novel evolutionary conserved neurotrophic factor (NTF) family. MANF has a unique structure and an unparalleled dual mode of action that differs from other known NTFs. Recent studies have shown that MANF protects cells from endoplasmic reticulum stress. In addition, an increasing number of studies have found MANF plays an important role in nervous system disease. This review focuses on MANF, summarizing its unique structure, potential signaling pathway, and role in neurological disease.

Association between social withdrawal and suicidal ideation in patients with major depressive disorder: The mediational role of emotional symptoms.

BACKGROUND: The study was designed to investigate the associations between social withdrawal, emotional symptoms, and suicide ideation in patients with major depressive disorder (MDD). METHODS: This cross-sectional study included 2678 MDD patients from the National Survey on Symptomatology of Depression (NSSD). Differences in the sociodemographic factors, clinical characteristics, suicide ideation, and emotional symptoms were compared in patients with different frequencies of social withdrawal. Pearson correlation, multiple linear regression analysis, and mediation analysis were employed to assess the contribution of social withdrawal to suicide ideation. RESULTS: MDD patients with a higher frequency of social withdrawal were prone to have a higher frequency of suicide ideation (p for trend <0.001) and history of suicide behavior (p for trend <0.001). Multiple linear regression analysis showed that there was a dose-response relationship between social withdrawal and suicide ideation in MDD patients, but this association became insignificant after adjusting for emotional symptoms. Mediation analysis suggested that all of the emotional symptoms had significant mediating effects on the association between social withdrawal and suicide ideation in MDD patients (p < 0.05). The magnitude of mediation varied between 4.3 % and 64.3 %, with the largest mediating effect in the feeling of despair (64.3 %), helplessness (41.2 %), and loneliness (40.0 %). CONCLUSION: Our study provides evidence that social withdrawal was a common clinical presentation and it may increase the risk for suicide through emotional symptoms in MDD patients. LIMITATIONS: Causal conclusions could not be drawn between social withdrawal, emotional symptoms, and suicide ideation because of the cross-sectional design of the study.

Correction: Undenatured type II collagen prevents and treats osteoarthritis and motor function degradation in T2DM patients and db/db mice.

Correction for 'Undenatured type II collagen prevents and treats osteoarthritis and motor function degradation in T2DM patients and db/db mice' by Fan Rui et al., Food Funct., 2021, 12, 4373-4391, https://doi.org/10.1039/D0FO03011B.

Vertebral refracture after percutaneous vertebroplasty for osteoporotic vertebral compression fractures with and without brace wearing: A retrospective study of 300 patients.

Background: The aim of the study was to examine the clinical incidence rate of vertebral body fractures after percutaneous vertebroplasty (PVP) with and without brace wearing and provide a new guiding ideology for preventing vertebral fractures after clinical surgeries. Methods: The retrospective analysis included 100 outpatients who underwent PVP between January 2017 and December 2018 without bracing after PVP surgeries (non-brace-wearing group). In total, 100 patients were paired into the rigid brace group and 100 patients were paired into the soft braces group according to propensity score matching. Seven independent variables were used in the soft and rigid brace group: age, sex, body mass index (BMI), visual analog scale (VAS), Oswestry Disability Index (ODI), and Cobb angle. The VAS, ODI, and Japanese Orthopaedic Association (JOA) scores were recorded preoperatively on the second day, after 1 month, after 3 months, and during the last follow-up postoperatively. We recorded the incidence of vertebral refracture in each of the three groups of patients and evaluated the effect of braces on postoperative fractures based on the ODI, VAS, and JOA scores. Results: All patients were followed up for 8-24 months (mean 22.4 months). Compared with the preoperative values, the age, sex, BMI, bone density, ODI, VAS, and Cobb angle between refracture and non-refracture were not statistically significant. The VAS, ODI, and JOA scores significantly increased in the brace-wearing group compared with those of the non-brace-wearing group (p < 0.05). The incidence of vertebral refracture in the brace-wearing group was lower than that in the non-brace-wearing group, between which there was a significant difference (p < 0.05). Three months postoperatively, the JOA score of the soft brace group was significantly higher than that of the rigid brace group (p < 0.05). During the last follow-up, it was found that there was no difference in the VAS score, the incidence of refracture, or ODI between the soft brace group and the rigid brace group (p > 0.05). The improvement in the JOA score of the soft brace group was better than that of the rigid brace group, between which there was a significant difference (p < 0.05). Conclusion: Braces can improve the prognosis of quality of life and postoperative subjective perception, whose presence can relieve postoperative residual pains. In contrast, patients can have a better medical experience wearing a soft brace.

Associations between gastrointestinal symptoms, medication use, and spontaneous drug discontinuation in patients with major depressive disorder in China.

BACKGROUND: The study was designed to investigate the associations between gastrointestinal (GI) symptoms, medication use, and spontaneous drug discontinuation (SDD) in patients with major depressive disorder (MDD). METHODS: This cross-sectional study included 3256 MDD patients from the National Survey on Symptomatology of Depression (NSSD). Differences in the sociodemographic factors, clinical characteristics, medication use, and self-reported reasons for SDD were compared in patients with different frequencies of GI symptoms. A multiple logistic regression analysis was employed to assess the contribution of GI symptoms to the risk of spontaneous drug discontinuation. RESULTS: MDD patients with a higher frequency of GI symptoms were prone to have higher proportions of mood stabilizer and benzodiazepine uses (ps for trend < 0.001) but a lower proportion of SNRI use (pfor trend < 0.001). With the increase in GI symptoms, patients were prone to report worries about long-term side effects (pfor trend < 0.001), with the patients stating ineffective treatments (pfor trend = 0.002) and intolerance of adverse drug reactions (pfor trend = 0.022) as the reasons for SDD. Compared with those patients without GI symptoms, all of the MDD patients with GI symptom frequencies of several days (OR = 1.317; 95 % CI: 1.045-1.660), more than half of all days (OR = 1.305; 95 % CI: 1.005-1.695), and nearly every day (OR = 1.820; 95 %: 1.309-2.531) had an increased risk of SDD. CONCLUSION: GI symptoms are highly associated with drug discontinuation in MDD patients. These findings may have important implications for clinical treatment options, as well as for drug adherence management, in MDD patients.

Effcacy-oriented compatibility for Tianma (), Yanlingcao () and Bingpian () on improving cerebral ischemia stroke by network pharmacology and serum pharmacological methods.

OBJECTIVE: To evaluate the compatibility of Tianma (, TM), Yanlingcao (, YLC) and Bingpian (, BP), and their efficacy in the treatment of cerebral ischemic stroke. METHODS: Network pharmacology was used to determine the compatibility of TM, YLC, and BP, and their potential mechanism. The middle cerebral artery occlusion (MCAO) rat model was used to evaluate the curative effect of the six combinations of TM, YLC, and BP (TZB1-TZB6) on cerebral ischemia, by using the weight matching method to form. The potential component changes of TM and YLC in the blood and brains of rats were analyzed using ultra performance liquid chromatography-mass spectrometry. Finally, molecular docking linked the results of animal experiments and network pharmacology, determining the potential component contributors of TM and YLC to treating ischemic stroke. RESULTS: TZB reduced the cerebral infarct volume and protected the nerve cells in MCAO rats. The components of TM and YLC were also identified in the blood and brain homogenate, and BP can facilitate the entry of the components of TM and YLC into the blood and brain. Diosgenin, pennogenin, and gastrodin induced effective binding activities with adenosine receptor a1. CONCLUSION: We investigate an approach that improves the means of folk prescription combined with multi technology that maybe promote the transformation of Chinese medicinal prescription into component-based Chinese medicine.

Undenatured type II collagen prevents and treats osteoarthritis and motor function degradation in T2DM patients and db/db mice.

Osteoarthritis (OA) has been scarcely researched among patients with diabetes mellitus. This study aims to confirm the preventive and therapeutic effects of undenatured type II collagen (UC II) on OA in aging db/db mice and in patients with T2DM. Firstly, aging db/db mice were randomly assigned to three groups: the UC II intervention (UC II) group, old model (OM) group and positive control group. Meanwhile db/m mice and young db/db mice were used as the normal control and young control groups, respectively. Secondly, fifty-five T2DM patients diagnosed with knee OA were randomly assigned to two groups: UC-II and placebo control groups. After a three-month intervention in both mice and T2DM patients, the subjects' gait and physical activities were assessed and the serum biomarkers including inflammatory cytokines, oxidative stress factors and matrix metalloproteinases (MMPs) were measured. Compared with the OM group mice, those in the UC II group showed a significantly greater superiority in terms of motor functions including the movement trajectories area (163.25 ± 20.3 vs. 78.52 ± 20.14 cm2), the tremor index (0.42 vs. 1.23), standing time (left hind: 0.089 ± 0.03 vs. 0.136 ± 0.04 s), swing (right front: 0.12 ± 0.02 vs. 0.216 ± 0.02 s), stride length (right hind: 7.2 ± 0.9 vs. 5.7 ± 1.1 cm), step cycle (right hind: 0.252 ± 0.05 vs. 0.478 ± 0.11 s) and cadence (14.12 ± 2.7 vs. 7.35 ± 4.4 steps per s). In addition, the levels of IL-4, IL-10, CTX- II and TGF-ß in the UC II group were 1.74, 2.23, 1.67 and 1.84 times higher than those in the OM group, respectively, while the levels of MMP-3 and MMP-13 in the UC II group were half those in the OM group. Correspondingly, UC II intervention significantly decreased the scores of pain, stiffness and physical function (p < 0.05), whereas the 6 MWT and total MET distances in the UC II group increased remarkably (p < 0.05). After a three-month period of intervention, the varus angle significantly decreased from 4.6 ± 2.0° to 3.0 ± 1.4° and the knee flexion range obviously increased from 57.9 ± 14.0° to 66.9 ± 10.4°. Importantly, the declining trend in the levels of hs-CRP and MDA and the incremental trend in the SOD level were consistent in the db/db mice and OA patients following UC II administration.

Prevalence of Congenital Heart Disease Amongst Schoolchildren in Southwest China.

OBJECTIVE: To investigate the prevalence and risk factors of congenital heart disease in Yunnan, China which has diverse ethnic groups. METHODS: This cross-sectional study enrolled 244,023 children from 2010 to 2015. To diagnose CHD, a conventional physical examination was used to screen suspicious cases, which were further confirmed by echocardiography. RESULTS: A total of 1695 children were diagnosed with CHD. The estimated prevalence was 6.94%. Atrial septal defects were the most common cardiac abnormalities. A higher prevalence of CHD was observed with preterm birth, low birth weight, maternal age ≥35 years, and high-altitude regions. The prevalence also showed differences between diverse ethnic groups. CONCLUSIONS: The prevalence of CHD in China may have ethnic differences.

Rational biosynthetic engineering for optimization of geldanamycin analogues.

Tailor made: We report the rational biosynthesis of C15 hydroxylated non-quinone geldanamycin analogues by site-directed mutagenesis of the geldanamycin polyketide synthase (PKS), together with a combination of post-PKS tailoring genes. Rational biosynthetic engineering allowed the generation of geldanamycin derivatives, such as DHQ3 illustrated in the figure, which had superior pharmacological properties in comparison to the parent compound. A rational biosynthetic engineering approach was applied to the optimization of the pharmacological properties of the benzoquinone ansamycin, geldanamycin. Geldanamycin and its natural or semisynthetic derivatives have the potential to serve as anticancer chemotherapeutic agents. However, these first-generation Hsp90 inhibitors share an unfavorable structural feature that causes both reduced efficacy and toxicity during clinical evaluation. We report the rationally designed biosynthesis of C15 hydroxylated non-quinone geldanamycin analogues by site-directed mutagenesis of the geldanamycin polyketide synthase (PKS), together with a combination of post-PKS tailoring genes. A 15-hydroxyl-17-demethoxy non-quinone analogue, DHQ3, exhibited stronger inhibition of Hsp90 ATPase activity (4.6-fold) than geldanamycin. Taken together, the results of the present study indicate that rational biosynthetic engineering allows the generation of derivatives of geldanamycin with superior pharmacological properties.

Rare Hereditary Klippel-Feil Syndrome and Arnold-Chiari Malformation Caused by Cervical Spondylotic Myelopathy.

BACKGROUND: A rare case of familial genetic disorder Klippel-Feil syndrome and Arnold-Chiari malformation caused by cervical spondylotic myelopathy was reported here. CASE DESCRIPTION: The reconstruction of stability and spinal cord decompression was achieved by anterior cervical discectomy, fusion, and internal fixation. CONCLUSIONS: Although the disease genetic characteristics have been studied, operation is necessary when it leads to abnormal neurologic symptoms and the surgery of surgery can have a beneficial outcome.

Risk factors for drug-resistant epilepsy: A systematic review and meta-analysis.

BACKGROUND: Drug resistant epilepsy (DRE) is very common among children and adults and studies had found some related risk factors for DRE, while the results were not consistent. The aim of this study was to identify risk factors for drug-resistant epilepsy. METHODS: Three electronic databases (Medline, Embase and Cochrane library) were searched to identify studies with a cohort design reporting on epidemiologic evidence regarding risk factors for DRE. RESULTS: The pooled prevalence of DRE in newly diagnosed epilepsy patients was 25% (95% CI 17-32%). Abnormal electroencephalography (EEG) (both slow wave and epileptiform discharges) (RR 2.80; 95% CI 1.95-4.0), status epilepticus (SE) (RR 11.60; 95% CI 7.39-18.22), symptomatic etiology (RR 3.36; 95% CI 2.53-4.46), multiple seizure types (RR 3.66; 95% CI 2.37-5.64) and febrile seizures (RR 3.43; 95% CI 1.95-6.02) were identified as strong risk factors for DRE. In addition, firm conclusions cannot be drawn for poor short-term outcomes of therapy, neurodevelopment delay and high initial seizure frequency for the heterogeneity of study results. The predictive effect of focus onset seizure was not stable after removing one study and switching the effect model. Age of onset was not risk factors for DRE. CONCLUSIONS: The current meta-analysis identified potential risk factors for DRE. The results may contribute to better prevention strategies and treatments for DRE.

Characterization of tailoring genes involved in the modification of geldanamycin polyketide in Streptomyces hygroscopicus JCM4427.

Geldanamycin and its analogs are important anticancer agents that inhibit the newly targeted, heat-shock protein (Hsp) 90, which is a chaperone protein in eukaryotic cells. To resolve which geldanamycin biosynthetic genes are responsible for particular post-polyketide synthase (PKS) processing steps and in which order the reactions occur, we individually inactivated candidate genes in Streptomyces hygroscopicus subsp. duamyceticus JCM4427, and isolated and elucidated the structures of intermediates from each mutant. The results indicated that gel7 governs at least one of the benzoquinone ring oxidation steps. In addition, gel16 was found to be involved in double-bond formation between C-4 and C-5 of 4,5-dihydrogeldanamycin, which confirmed our previous findings that this double bond reduced during the post-PKS modification of the polyketide assembly. In addition, pro-geldanamycin, which does not possess a double bond at C-4/5, was purified from the gel7 and 8 double-gene-inactivated mutant.

Indirect comparison of third-generation antiepileptic drugs as adjunctive treatment for uncontrolled focal epilepsy.

PURPOSE: Eslicarbazepine (ESL), Lacosamide (LAC), Perampanel (PER) and Brivaracetam (BRV), have recently been marketed as third-generation antiepileptic drugs (AEDs). We conducted a meta-analysis to indirectly compare overall efficacy and tolerability between third-generation AEDs in uncontrolled focal epilepsy. METHODS: We performed an online database search using Pubmed, Embase, Cochrane Online Library, and Clinicaltrial.gov for all available randomized controlled trials (RCTs) that investigated the therapeutic effects over a range of AED doses versus placebo. We then compared clinical efficacy and tolerability between these newer AEDs using Indirect Treatment Comparison software. RESULTS: Nineteen RCTs with a total of 7245 patients were included in our study. There were no significant differences in the risk difference of 50% responder rates and seizure free rates between third generation AEDs, regardless of dose. The risk of treatment emergent adverse events was significantly higher with ESL and PER treatment compared to BRV at all doses combined. Withdrawal rates due to adverse events were also significantly higher in patients treated with the highest doses of LAC and PER versus BRV, while treatment with ESL or LAC was related to higher withdrawal rates versus BRV when all doses were combined. CONCLUSIONS: Our analysis suggested there were no significant differences in efficacy between third generation AEDs in uncontrolled focal epilepsy. BRV may have the best tolerability profile. The other AEDs were associated with a higher risk for intolerable adverse, especially when taken at a high doses. The results from these indirect comparisons warrant further examination and verification through future well-designed trials.

[Epidemiological investigation on congenital heart disease in several regions of Yunnan province].

OBJECTIVE: To investigate the distribution of congenital heart disease (CHD) aged 3 - 18 in several regions of Yunnan province. METHODS: Cross-rectional studies were carried out among 48 638 children from Xishuangbanna, Dali, Baoshan Longling, Luxi Mangshi and Gejiu in Yunnan province with stratified, clustered sampling. RESULTS: The overall morbidity of CHD was 5.08 per thousand with 5.09 per thousand in males and 5.07 per thousand in females. Morbidity rates in different regions were 2.75 per thousand in Xishuangbanna, 7.85 per thousand in Dali, 9.59 per thousand in Baoshan Long ling, 4.80 per thousand in Gejiu, 16.99 per thousand in Luxi Wuchalu. However, in the same area, rates were different among different residents:3.25 per thousand in Gejiu, and was 9.10 per thousand in Laochang stannum mine, 11.20 per thousand in Datunxuanchang; 5.74 per thousand at the city of Baoshan Longling, 11.35 per thousand at countryside; 4.90 per thousand at the city of Dali, 8.71 per thousand at countryside; 1.69 per thousand at the city of Xishuangbanna, 4.40 per thousand at country. Morbidity rates in different ethnic groups were as follows: 5.39 per thousand in Dai, 6.83 per thousand in Jinuo, 0 per thousand in Hani, 8.12 per thousand in Bai, 14.18 per thousand in Jingpo. CONCLUSION: There were significant regional and ethnic differences seen in Yunnan on the mobidity of CHD which was different from the domestic literature reported.