The effect of transcranial magnetic stimulation on cognitive function in post-stroke patients: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Transcranial magnetic stimulation (TMS) is considered as a promising treatment option for post-stroke cognitive impairment (PSCI).Some meta-analyses have indicated that TMS can be effective in treating cognitive decline in stroke patients, but the quality of the studies included and the methodologies employed were less than satisfactory. Thus, this meta-analysis aimed to evaluate the efficacy and safety of TMS for treating post-stroke cognitive impairment. METHODS: We searched online databases like PubMed, Embase, Cochrane Library, and Web of Science to retrieve randomized controlled trials (RCTs) of TMS for the treatment of patients with PSCI. Two independent reviewers identified relevant literature, extracted purpose-specific data, and the Cochrane Risk of Bias Assessment Scale was utilized to assess the potential for bias in the literature included in this study. Stata 17.0 software was used for data analysis. RESULTS: A total of 10 studies involving 414 patients were included. The results of the meta-analysis showed that TMS was significantly superior to the control group for improving the overall cognitive function of stroke patients (SMD = 1.17, 95% CI [0.59, 1.75], I2 = 86.1%, P < 0.001). Subgroup analyses revealed that high-frequency rTMS (HF-rTMS), low-frequency rTMS (LF-rTMS), and intermittent theta burst stimulation (iTBS) all have a beneficial effect on the overall cognitive function of stroke patients. However, another subgroup analysis failed to demonstrate any significant advantage of TMS over the control group in terms of enhancing scores on the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) and Rivermead Behavioral Memory Test (RBMT) scales. Nonetheless, TMS demonstrated the potential to enhance the recovery of activities of daily living in stroke patients, as indicated by the Modified Barthel Index (MBI) (SMD = 0.76; 95% CI [0.22, 1.30], I2 = 52.6%, P = 0.121). CONCLUSION: This meta-analysis presents evidence supporting the safety and efficacy of TMS as a non-invasive neural modulation tool for improving global cognitive abilities and activities of daily living in stroke patients. However, given the limited number of included studies, further validation of these findings is warranted through large-scale, multi-center, double-blind, high-quality randomized controlled trials. PROSPERO REGISTRATION NUMBER: CRD42022381034.

Modified Suanzaoren decoction in treating post-stroke cognitive impairment with comorbid insomnia symptoms: A clinical trial.

BACKGROUND: Cognitive impairment and insomnia are common complications for stroke patients, and often coexist without effective therapy. Modified Suanzaoren decoction (M-SZRD), derived from a famous classic prescription, has been used as an alternative treatment for these patients. The objective of this study is to investigate the effectiveness of M-SZRD in treating post-stroke cognitive impairment with comorbid insomnia symptoms. METHODS: A total of 80 participants were randomly assigned into 2 groups to 40 cases in the treatment group (treated with modified Suanzaoren decoction) and 40 cases in the control group (treated with zolpidem). The intervention period was 4 weeks. Cognitive function, sleep quality, depression, and anxiety disorders were evaluated in both groups before and after treatment. Clinical assessment of patients with stroke included National Institutes of Health Stroke Scale and Barthel Index evaluations. Hormone levels of the hypothalamic-pituitary-adrenal and hypothalamus-pituitary-thyroid axis were also measured. RESULTS: Out of the total 80 participants, 5 withdrew during the experiment and did not complete the study, leaving 75 patients for analysis to 38 in the treatment group and 37 in the control group. The findings showed that M-SZRD was more effective than the control group in improving cognitive function (P = .006). However, both groups were found to have a similar effect in improving insomnia (P = .323). There was no significant difference between the 2 groups in terms of activities of daily living and National Institutes of Health Stroke Scale improvement. M-SZRD was superior to the control group in improving depression state (P = .034), but when including dropouts in the intention-to-treat analysis, the difference was not statistically significant (P = .150). Furthermore, the M-SZRD group was better than the control group in reducing cortisol levels (P = .036), and the improvement in serum-free triiodothyronine (FT3) levels was also more significant in the M-SZRD group than in the control group (P = .0007). CONCLUSION: M-SZRD is a more effective treatment for improving cognitive function in patients with post-stroke cognitive impairment and comorbid insomnia symptoms, possibly by regulating the cortisol levels of the hypothalamic-pituitary-adrenal axis and FT3 levels of the hypothalamus-pituitary-thyroid axis.

Apigenin reduces the suppressive effect of exosomes derived from irritable bowel syndrome patients on the autophagy of human colon epithelial cells by promoting ATG14.

BACKGROUND: Inflammatory bowel disease (IBS) is a chronic disorder of the gastrointestinal tract. Exosomes have been involved in various pathological processes including IBS. Apigenin has been reported to suppress inflammatory bowel disease (IBS). However, the regulatory roles of exosomes derived from IBS patients (IBS-exos) on human colon epithelial cells are still unclear. METHODS: Exosomes were collected from IBS patients (IBS-exos) and co-cultured with CACO-2 cells. Apigenin was used to treat IBS-exos-treated CACO-2 cells. By exploring the public data bank, we figured out the regulators control the autophagy of CACO-2 cells. RESULTS: Administration of apigenin dose-dependently abolished the inhibitory effect of IBS-exo on the autophagy of CACO-2 cells. A mechanistic study showed that miR-148b-3p bound to 3'UTR to suppress ATG14 and decrease autophagy. Moreover, results suggested that ATG14 overexpression promoted the autophagy of CACO-2 cells in the presence of miR-148b-3p mimic. CONCLUSION: The current study showed that apigenin dose-dependently abolished the inhibitory effect of IBS-exo on CACO-2 cell autophagy by regulating miR-148b-3p/ATG14 signaling.

Treadmill training attenuates pyroptosis in rats with cerebral ischemia/reperfusion injury.

Objectives: Few studies have investigated the mechanism by which exercise training promotes neural repair during rehabilitation after stroke. In this study, we evaluated the neuroprotective effects of exercise training and pyroptosis-associated factors in the penumbra and elucidated the possible mechanisms. Materials and Methods: Neurological deficits, body weight, and the infarct size were evaluated, and haematoxylin-eosin (HE) staining was performed. Western blotting and immunofluorescence staining were used to assess NOD-like receptor family pyrin domain-containing 3 (NLRP3) and caspase-1 levels. Interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) levels were assessed by enzyme-linked immunosorbent assay (ELISA). B-cell lymphoma 2 (bcl-2) and bax protein levels were measured by Western blotting, and terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining was used to evaluate apoptotic cells. Results: Exercise training decreased neurological deficits and the infarct size in MCAO rats Moreover, NLRP3 inflammasome-associated protein levels in the peri-infarct cortex were decreased by exercise training. Exercise training decreased the serum concentrations of IL1ß and IL18, upregulated bcl-2, downregulated bax, and reduced the TUNEL index. Conclusion: Exercise training suppresses NLRP3 inflammasome activity and inhibits pyroptosis to protect against cerebral ischaemic injury. Exercise training can also suppress apoptosis, which may be the target of exercise-induced neuroprotection, thereby reducing brain injury.

Effect of the Interaction between Depression and Sleep Disorders on the Stroke Occurrence: An Analysis Based on National Health and Nutritional Examination Survey.

OBJECTIVE: To investigate the effect of the interaction between depression and sleep disorders on the stroke occurrence based on the data from the National Health and Nutritional Examination Survey (NHANES). METHODS: Seven cycles of 2-year NHANES data (2005-2018) were analyzed in this study. Univariate analysis was first performed between the stroke and nonstroke patients, and then, multivariate logistic regression models were conducted to analyze the association of depression, sleep disorders, and their interactions with stroke occurrence. RESULTS: A total of 30473 eligible participants were included in this study, including 1138 (3.73%) with stroke and 29335 (96.27%) with nonstroke. Except sex, the differences were all significant between the stroke and nonstroke patients in baseline information (all P < 0.001). Depression (odds ratio (OR): 2.494, 95% confidence interval (CI): 2.098-2.964), depression severity (moderate, OR: 2.013, 95% CI: 1.612-2.514; moderately severe, OR: 2.598, 95% CI: 1.930-3.496; severe, OR: 5.588, 95% CI: 3.883-8.043), and sleep disorders (OR: 1.677, 95% CI: 1.472-1.910) were presented to be associated with an increased risk of stroke after correcting all the confounders. The logistic regression analysis showed that there was a synergic, additive interaction between depression and sleep disorders on the stroke occurrence, and the proportion of stroke patients caused by this interaction accounted for 27.1% of all the stroke patients. CONCLUSION: Depression, depression severity, and sleep disorders are all independently associated with a high risk of stroke. The interaction between depression and sleep disorders can synergistically increase the stroke occurrence.

Drug-induced hepatotoxicity linked to zoledronic acid in the treatment of an elderly man with primary osteoporosis.

Zoledronic acid (ZA), an intravenous bisphosphonate, has been widely used for the treatment of osteoporosis. ZA is generally well tolerated, and ZA-related hepatotoxicity is rare. We report a case of hepatotoxicity after ZA infusion in an elderly male patient with primary osteoporosis. The patient had femoral neck and vertebral fractures, and 3 days after ZA 5-mg infusion, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased 23.4- and 15.3-fold, respectively, compared with pre-treatment values. Hepatoprotective agents were administered, and liver enzymes were back to near normal range 9 days later. This case report shows the possible hepatic adverse effects related to ZA infusion. The mechanism of hepatotoxicity caused by ZA is not clear. Acute-phase reaction after ZA infusion may play a role in hepatotoxicity, which should be taken into consideration, especially for the elderly.

Intensive treadmill training promotes cognitive recovery after cerebral ischemia-reperfusion in juvenile rats.

Rehabilitation training is routine for children who experience stroke, but its protective mechanism remains unclear. To study the effect of treadmill training intensity on hippocampal synaptic plasticity after cerebral ischemia, a model of middle cerebral artery occlusion (MCAO)/reperfusion was established in young rats to simulate childhood ischemic stroke. The rats were randomly allocated into five groups: sham operation, MCAO, low-intensity exercise and MCAO (5 m/min), medium-intensity exercise and MCAO (10 m/min), and high-intensity exercise and MCAO (15 m/min). Intervention was continued for 14 days, and a series of experimental tests were conducted. After MCAO, the juvenile rats exhibited a series of morphological and functional alterations, including changes in their neurobehavior and cerebral infarct volumes. Compared with control rats, MCAO rats had a longer escape latency and crossed fewer platforms in the water maze test and exhibited decreased hippocampal neuron density and Synapsin I and PSD95 expression. Furthermore, MCAO rats exhibited synapse morphology changes and abnormal serum levels of lactic acid and corticosterone. Treadmill training effectively reduced the neurobehavioral scores and cerebral infarction volumes, with medium-intensity training showing the best effect. Treadmill training shortened the escape latency, increased the number of platform crossings, and improved the spatial cognitive abilities of the rats, with the medium intensity training having the best effect on spatial learning/memory efficiency. Treadmill training increased the neuron density in the hippocampus, with the medium-intensity training resulting in the highest density. Treadmill training had a positive effect on the expression of Synapsin I and PSD95, with the medium-intensity training showing the strongest effect. Treadmill training improved the sub-microstructure synapse morphology, with the medium-intensity training demonstrating the best effect. Treadmill training increased the plasma levels of lactic acid and corticosterone, with the high-intensity training having the most obvious effect. Treadmill training can provide neuroprotection by promoting hippocampal synaptic plasticity, with medium-intensity training showing the most optimal effects.

Green synthesis of κ-carrageenan@Ag submicron-particles with high aqueous stability, robust antibacterial activity and low cytotoxicity.

Silver nanoparticles (AgNPs) are effective antimicrobial reagent, especially for the treatment of multidrug-resistant microorganisms. However, it is difficult to remove the residual harmful reducing agents in AgNPs synthesized by the traditional chemical reduction method. In addition, AgNPs exhibit cytotoxicity when exposed directly to cells for biomedical applications and will rapidly aggregate in aqueous environment. Herein, we develop a new route to synthesize submicron-particles containing AgNPs (κC@Ag MPs) with high aqueous stability, robust antibacterial activity and low cytotoxicity. AgNPs were firstly greenly synthesized using κ-carrageenan as environmental friendly reducing and stabilizing agent under heating in aqueous solution. Then the AgNPs were immobilized in the net of κ-carrageenan by adding KCl to obtain κC@Ag MPs. The results indicated that κC@Ag MPs were quite stable without any agglomeration and precipitation in aqueous solution for more than three months. κC@Ag MPs exhibited robust antibacterial activity against Gram-positive and Gram-negative bacteria, even better than that of pure AgNPs. Notably, κC@Ag MPs maintained the long-lasting retention of antibacterial activity. In addition, κC@Ag MPs possessed well cytocompatibility towards the L02 and L929 cells. Overall, κC@Ag MPs may have prospective application as effective and sustainable antibacterial agent in biomedical fields.

Effect of simplified Tai Chi exercise on relieving symptoms of patients with mild to moderate Parkinson's disease.

BACKGROUND: Tai Chi, a kind of physical exercise, may act as a non-pharmacologic approach to reducing the symptoms of Parkinson's disease. This study was conducted to investigate the effect of simplified Tai Chi training plus routine exercise on motor and non-motor symptoms in patients with mild to moderate Parkinson's disease in comparison with routine exercise regimen alone. METHODS: Forty-one outpatients and inpatients with Parkinson's disease (PD) were randomized into Tai Chi group (N.=19) and routine exercise group as control group (N.=22) for 12 weeks. The Tai Chi group included both Tai Chi traning and routine exercise. Motor and non-motor functions were assessed. Motor function was evaluated by Unified Parkinson's Disease Rating Scale part III (UPDRS-III) and Berg Balance Scale (BBS). The non-motor symptoms like quality of life, sleep quality, depression and anxiety state, cognitive function were assessed by Parkinson's Disease Questionnaire-39 (PDQ-39), Parkinson's Disease Sleep Scale (PDSS), Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Montreal Cognitive Assessment (MOCA) respectively. RESULTS: After 12 weeks of intervention, participants in both Tai Chi and routine exercise groups gained effects in UPDRS-III, BBS, PDQ-39, PDSS and HAMD compared to the baseline. However, significant improvements between Tai Chi group and routine exercise group were only found in PDSS (P=0.029) and MoCA (P=0.024). CONCLUSIONS: Tai Chi training plus routine exercise might therefore be an ideal alternative non-pharmacological approach for the motor and non-motor symptoms of PD patients, and especially be more useful for the improvement of sleep quality and cognitive function in Parkinson's disease compared with routine exercise regimen alone.

Elevated homocysteine level and prognosis in patients with acute coronary syndrome: a meta-analysis.

Objective: Controversial results exist with respect to the association between elevated homocysteine level and adverse prognosis in acute coronary syndrome (ACS) patients. We performed a meta-analysis to evaluate the prognostic value of homocysteine level on ACS patients. Materials and methods: A comprehensive literature search of PubMed and Embase databases was conducted prior to August 2018. Prospective observational studies reporting the association of baseline homocysteine level with major adverse cardiovascular events (MACE), cardiovascular or all-cause mortality in ACS patients were selected. Pooled risk ratio (RR) and corresponding 95% confidence intervals (CI) were calculated for the highest versus the lowest homocysteine level. Results: Ten studies including 4120 ACS patients were identified. ACS patients with the highest homocysteine level had an increased risk of MACE (RR 2.01; 95% CI 1.53-2.64) and all-cause mortality (RR 2.05; 95% CI 1.50-2.79) after controlling confounding factors. However, the association between elevated homocysteine level and cardiovascular mortality (RR 1.08; 95% CI 0.83-1.39) was not statistically significant. Conclusions: Elevated homocysteine level was associated with an increased risk of MACE and all-cause mortality among ACS patients. However, the association of elevated homocysteine level with cardiovascular mortality in ACS patients should be further confirmed in future studies.

Effects of carboxyl and aldehyde groups on the antibacterial activity of oxidized amylose.

Dialdehyde-amyloses, dicarboxyl-amyloses and dialdehyde-carboxyl-amyloses with different oxidation levels were prepared and used to study the effects of aldehyde and carboxyl groups on the antibacterial activity of oxidized amyloses. The results showed that dicarboxyl-amyloses presented antibacterial activity through acidic pH effect produced by carboxyl groups, which was easily reduced or eliminated by adjusting pH. Dialdehyde-amyloses possessed a broad-spectrum antibacterial activity owing to the reactivity of aldehyde groups rather than acidic pH effect. Aldehyde would irreversibly damage bacterial cell wall and cytoplasmic membrane, resulting in decay and death of bacterial cells. It is interesting that the antibacterial properties of dialdehyde-carboxyl-amyloses were improved to some extent compared to dialdehyde-amyloses. The improvement of antibacterial effect of dialdehyde-carboxyl-amyloses may be due to the increasing dispersibility endowed by carboxyl groups, which could effectively enhance the interaction between dialdehyde-carboxyl-amyloses and bacteria. As a result, carboxyl group could act as a promising synergistic group against bacteria with aldehyde group.

Preparation, characterization and antibacterial activity of oxidized κ-carrageenan.

The oxidized κ-carrageenans with different oxidation levels were prepared through the hydrogen peroxide and copper sulfate redox system. The oxidation level of oxidized κ-carrageenan was successfully controlled by adjusting the dosage of hydrogen peroxide. The results showed that the microtopography of oxidized κ-carrageenan changed from rough granules to smooth flakes, mainly resulting from the easily melting property of oxidized κ-carrageenan induced by introduced carboxyl and aldehyde groups. Especially, the antibacterial activity of oxidized κ-carrageenans against Gram-positive bacteria (Staphylococcus aureus and Listeria monocytogenes) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) was systematically investigated. The results showed that the oxidized κ-carrageenan could damage the bacterial cell wall and cytoplasmic membrane and suppress the growth of both Gram-positive and Gram-negative bacteria. The oxidized κ-carrageenan possessed broad-spectrum antibacterial activity, which may be used as a new antibacterial agent.

Effect of Tianshu capsule in treatment of migraine: a meta-analysis of randomized control trials.

OBJECTIVE: To review the efficacy of Tianshu capsule in the treatment of migraine. METHODS: Retrieving papers from Pubmed, cochrane central register of controlled trials (CENTRAL), Weipu database (VIP), China biology medicine (CBM), China national knowledge infrastructure (CNKI), and Wanfang Data. Two reviewers retrieved and extracted the information independently. Retrieval time scale is up to August 2012. Software Review Manager 5.1 was used for analysis. RESULTS: A total of 10 studies including 937 migraine patients. The merged data shows Tianshu capsule had a higher effective rate in treating migraine, and there is no significant heterogeneity between Tianshu capsule group and control group (Chi2 = 6.33, df = 9, P = 0.71, I2 = 0%), OR = 4.18 [95% CI (2.93,5.95)]. Tianshu capsule alone compared to conventional therapy also showed advantages, and there was low heterogeneity (chi2 = 4.53, df = 3, P = 0.21, I2 = 34%), OR = 3.95 [95% CI (2.32, 6.72)]. Meta-analysis results show that clinical efficacy of Tianshu capsule was better than that of the control group in the treatment of migraine and there was a significant difference (P < 0.000 01). CONCLUSION: Tianshu capsule had better efficacy in the treatment of migraine with fewer adverse effects.

Meta-analysis of traditional Chinese medicine in treating functional dyspepsia of liver-stomach disharmony syndrome.

OBJECTIVE: To systematically assess the clinical effectiveness of traditional Chinese medicine (TCM) in the treatment of functional dyspepsia (FD) of liver-stomach disharmony syndrome by meta-analysis. METHODS: Random controlled trials (RCTs) were retrieved from databases, including Pubmed, China national knowledge infrastructure, Wanfang Data, VIP Information, and the Cochrane Library. Trials were selected according to inclusion criteria. The effects of traditional Chinese medicine (TCM) versus prokinetic agents in the treatment of functional dyspepsia (FD) of liver-stomach disharmony syndrome were compared by meta-analysis. RevMan 5.0.24 was used for data analysis. The effective rate was assessed by odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. The cure rate was analyzed by the Peto OR. Simple statistical analysis was chosen to assess the frequency of prescribed Chinese herbs in treating this syndrome. RESULTS: Thirteen trials were included, involving 1153 patients, and these were of poor methodological quality. Twelve studies mentioned the effective rate and cure rate. TCM therapy showed a better clinical effect rate compared with that with prokinetic agents [OR: 3.2, 95% CI (2.27, 4.51)]. The TCM group also had a better cure rate than that in the group of prokinetic agents [Peto OR: 2.26, 95% CI (1.61, 3.18)]. With regard to the frequency of Chinese herbs used in these 13 trials, Baishao (Radix Paeoniae), Chaihu (Radix Bupleuri), and Gancao (Radix Glycyrrhizae) were mostly prescribed, followed by Xiangfu (Rhizoma Cyperi), Zhishi (Fructus Aurantii Immaturus), Zhiqiao (Fructus Aurantii), Foshou (Citrus medica var. sarcodactylis), and Chenpi (Pericarpium Citri Reticulatae). No serious adverse effects were reported. CONCLUSION: TCM therapy shows a superior effective rate and cure rate compared with those in prokinetic agents in the treatment of FD of liver-stomach disharmony syndrome. However, further strictly designed RCTs are required because of the poor quality of included trials.