In recent years, non-invasive brain stimulation has been widely used in clinical rehabilitation due to its safe and non-invasive features.Particularly for stroke patients, this technique has become a new type of rehabilitation by virtue of its role in improving gait disorders, aphasia, dysphagia, and other complications. Previous research on stroke rehabilitation mainly focused on the cerebral cortex, while the recent evidences suggest that the cerebellum, with its rich synaptic plasticity and extensive structural and functional connectivity with the brain, has emerged as a promising target for non-invasive intervention in stroke rehabilitation. Non-invasive stimulation of the cerebellum is expected to improve patients' impaired function and quality of life. This review discusses the possible mechanisms and clinical applications of non-invasive cerebellar stimulation technology in regulating stroke rehabilitation, aiming to provide new treatment directions and application value for individualized stroke rehabilitation.

The cerebellum plays a critical role not only in motor control but also in reward processing, emotional regulation, and addictive behaviors.Addictive behaviors alter the cerebellum’s neurotransmitter systems and synaptic connections, leading to dysfunction and reinforcing the persistence of addiction.This review summarizes the anatomical and functional foundations of the cerebellum in the reward circuitry and explores how cerebellar synaptic plasticity influences brain function in both substance and behavioral addictions. Furthermore, the potential role of the cerebellum in the progress of addiction and its clinical application prospects in addiction treatment are also discussed.

In recent years, non-invasive brain stimulation has been widely used in clinical rehabilitation due to its safe and non-invasive features.Particularly for stroke patients, this technique has become a new type of rehabilitation by virtue of its role in improving gait disorders, aphasia, dysphagia, and other complications. Previous research on stroke rehabilitation mainly focused on the cerebral cortex, while the recent evidences suggest that the cerebellum, with its rich synaptic plasticity and extensive structural and functional connectivity with the brain, has emerged as a promising target for non-invasive intervention in stroke rehabilitation. Non-invasive stimulation of the cerebellum is expected to improve patients' impaired function and quality of life. This review discusses the possible mechanisms and clinical applications of non-invasive cerebellar stimulation technology in regulating stroke rehabilitation, aiming to provide new treatment directions and application value for individualized stroke rehabilitation.

The cerebellum plays a critical role not only in motor control but also in reward processing, emotional regulation, and addictive behaviors.Addictive behaviors alter the cerebellum’s neurotransmitter systems and synaptic connections, leading to dysfunction and reinforcing the persistence of addiction.This review summarizes the anatomical and functional foundations of the cerebellum in the reward circuitry and explores how cerebellar synaptic plasticity influences brain function in both substance and behavioral addictions. Furthermore, the potential role of the cerebellum in the progress of addiction and its clinical application prospects in addiction treatment are also discussed.

Objective:To investigate the role and molecular mechanisms of transcription factor EB (TFEB) and its target genes in the treatment of multiple myeloma (MM) with bortezomib.Methods:TFEB target genes were predicted using the GTRD database (http://gtrd.biouml.org/), identifying Ptch1 gene for further study. Expression changes of Ptch1 in RPMI8226 and U266 MM cell lines after bortezomib treatment were assessed by real time fluorogenic quantitative PCR (RT-qPCR) and Western blot. RPMI8226 and U266 cell lines were transfected with siRNA-TFEB, and mRNA and protein levels of key factors (Ptch1, Gli1) in the Ptch1/Hedgehog signaling pathway were measured by RT-qPCR and Western blot. Furthermore, Ptch1 was overexpressed in MM cell lines via lentiviral transduction. Autophagy was evaluated by acridine orange staining, and protein levels of LC3B, Beclin-1, and Lamp-1 were measured by Western blot. Lysosomal quantity changes were assessed by lysosomal fluorescent probes.Results:Bortezomib (6.0×10 -6 mmol/L, 24 h) significantly reduced Ptch1 mRNA and protein levels in both cell lines compared with blank control group (all P<0.05). siRNA-TFEB transfection reversed bortezomib’s inhibition of Hedgehog pathway key factors Ptch1 and Gli. Ptch1 overexpression in bortezomib-treated RPMI8226 and U266 cells significantly reduced the relative expression of autophagy-related proteins LC3B, Beclin-1, and Lamp-1 (all P=0.001). Acridine orange staining showed fewer acidic vesicular organelles within two cell lines (all P=0.001). The relative fluorescence expressions of lysosomal probes reflecting the number of lysosomes were also decreased ( P values of RPMI8226 and U266 cell lines were 0.001 and 0.007, respectively) . Conclusion:The knockdown of TFEB can specifically promote the expression of the Ptch1/Hedgehog signaling pathway, thereby reducing bortezomib-induced autophagy in MM cells and reversing the inhibitory effect of bortezomib on the proliferation of MM cell lines.

Objective:To investigate the role and molecular mechanisms of transcription factor EB (TFEB) and its target genes in the treatment of multiple myeloma (MM) with bortezomib.Methods:TFEB target genes were predicted using the GTRD database (http://gtrd.biouml.org/), identifying Ptch1 gene for further study. Expression changes of Ptch1 in RPMI8226 and U266 MM cell lines after bortezomib treatment were assessed by real time fluorogenic quantitative PCR (RT-qPCR) and Western blot. RPMI8226 and U266 cell lines were transfected with siRNA-TFEB, and mRNA and protein levels of key factors (Ptch1, Gli1) in the Ptch1/Hedgehog signaling pathway were measured by RT-qPCR and Western blot. Furthermore, Ptch1 was overexpressed in MM cell lines via lentiviral transduction. Autophagy was evaluated by acridine orange staining, and protein levels of LC3B, Beclin-1, and Lamp-1 were measured by Western blot. Lysosomal quantity changes were assessed by lysosomal fluorescent probes.Results:Bortezomib (6.0×10 -6 mmol/L, 24 h) significantly reduced Ptch1 mRNA and protein levels in both cell lines compared with blank control group (all P<0.05). siRNA-TFEB transfection reversed bortezomib’s inhibition of Hedgehog pathway key factors Ptch1 and Gli. Ptch1 overexpression in bortezomib-treated RPMI8226 and U266 cells significantly reduced the relative expression of autophagy-related proteins LC3B, Beclin-1, and Lamp-1 (all P=0.001). Acridine orange staining showed fewer acidic vesicular organelles within two cell lines (all P=0.001). The relative fluorescence expressions of lysosomal probes reflecting the number of lysosomes were also decreased ( P values of RPMI8226 and U266 cell lines were 0.001 and 0.007, respectively) . Conclusion:The knockdown of TFEB can specifically promote the expression of the Ptch1/Hedgehog signaling pathway, thereby reducing bortezomib-induced autophagy in MM cells and reversing the inhibitory effect of bortezomib on the proliferation of MM cell lines.

Objective:To investigate the association between serum uric acid,pulmonary function and airflow obstruction in Chinese Taiwan healthy subjects.Methods:All the cross-sectional analysis was performed in the population over 40 years old using the physical examination data of Chinese Taiwan MJ Health Resource Center between 1996 and 2016 stratification by gender.The correlation analyses between serum uric acid were done and multivariate Logistic regression analysis was used to explore the effect of serum uric acid on airflow obstruction.Results:A total of 35 465 people were included in the study,in-cluding 16 411 men and 19 054 women.Among them,the serum uric acid concentration of men was higher than that of women,and the serum uric acid concentration of the people with airflow obstruction was higher than that of the people without airflow obstruction.There was a negative correlation between serum uric acid level and the forced expiratory volume in one second(FEV1)and the force vital capacity(FVC)in women(P＜0.05),but in men the correlation didn't exist(P＞0.05).After adjusting for age,education,smoking status,drinking status,work strength,body mass index,history of cough,his-tory of hypertension,history of diabetes,history of dyslipidemia,white blood cells and blood albumin,the airflow obstruction in women was more likely to exist with the serum uric acid elevated(OR=1.12,95％CI:1.02-1.22,P＜0.05).The results showed that women with hyperuricemia were more likely to have airflow obstruction than those without hyperuricemia(OR=1.36,95％CI:1.06-1.75,P＜0.05).There was no correlation between serum uric acid concentration and airflow obstruction in men(OR=1.04,95％CI:0.96-1.13,P＞0.05),also the hyperuricemia and airflow obstruction(OR=1.12,95％CI:0.89-1.39,P＞0.05).Conclusion:There is a negative correlation between serum uric acid and FEV1 and FVC in relatively healthy women,and there is an association between elevated serum uric acid and airflow obstruction in women,but not in men.Further prospective studies are needed to explore whether high serum uric acid level can increase the risk of airflow obstruction.

Objective:Differences between randomized controlled trial (RCT) results and real world study (RWS) results may not represent a true efficacy-effectiveness gap because efficacy-effectiveness gap estimates may be biased when RWS and RCT differ significantly in study design or when there is bias in RWS result estimation. Secondly, when there is an efficacy- effectiveness gap, it should not treat every patient the same way but assess the real-world factors influencing the intervention's effectiveness and identify the subgroup likely to achieve the desired effect.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:Ten articles were included to discuss how to use the RCT research protocol as a template to develop the corresponding RWS research protocol. Moreover, based on correctly estimating the efficacy-effectiveness gap, evaluate the intervention effect in the patient subgroup to confirm the subgroup that can achieve the expected benefit-risk ratio to bridge the efficacy-effectiveness gap.Conclusion:Using real-world data to simulate key features of randomized controlled clinical trial study design can improve the authenticity and effectiveness of study results and bridge the efficacy-effectiveness gap.

Objective:Randomized controlled trials (RCT) usually have strict implementation criteria. The included subjects' characteristics of the conditions for the intervention implementation are quite different from the actual clinical environment, resulting in discrepancies between the risk-benefit of interventions in actual clinical use and the risk-benefit shown in RCT. Therefore, some methods are needed to enhance the extrapolation of RCT results to evaluate the real effects of drugs in real people and clinical practice settings.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:A total of 12 articles were included. Three methods in the included literature focused on: ①improving the design of traditional RCT to increase population representation; ②combining RCT Data with real-world data (RWD) for analysis;③calibrating RCT results according to real-world patient characteristics.Conclusions:Improving the design of RCT to enhance the population representation can improve the extrapolation of the results of RCT. Combining RCT data with RWD can give full play to the advantages of data from different sources; the results of the RCT were calibrated against real-world population characteristics so that the effects of interventions in real-world patient populations can be predicted.

Objective:Diabetic retinopathy (DR) has been reported as the leading cause of blindness among diabetic adults, which is closely related to poor quality of life and increased burden of disability. This study aimed to aggregate the optimally available evidence on modifiable risks of DR.Methods:Until June 2023, PubMed, Cochrane Library, CNKI, and Wanfang databases were used to retrieve Meta-analysis about various risk factors for DR, and Meta-analysis were analyzed and summarized. R 4.3.2 software was used for each Meta-analytic association to calculate the effect size, 95% CI, heterogeneity, small-study effects, excess significance bias, and 95% prediction intervals. The credibility of significant evidence was graded. Results:We captured 23 eligible papers (72 associations) covering a wide range of medication use, concomitant diseases, daily intervention, biomarkers, lifestyle, and physical measurement index. Among them, higher HbA1c variability ( RR=1.45, 95% CI: 1.26-1.66) and urine microalbumin positive ( OR=2.44, 95% CI: 1.99-2.97) were convincing (grade Ⅰ) evidence, and insulin use ( RR=3.48, 95% CI: 2.14-5.67) was highly suggestive (grade Ⅱ) evidence. Moreover, hypertension ( OR=2.03, 95% CI: 1.06-3.97), poor glycemic control ( OR=4.35, 95% CI: 1.47-12.85), positive macroalbuminuria ( OR=8.42, 95% CI: 3.52-20.15), long sleep duration ( OR=2.05, 95% CI: 1.37-3.05), vitamin D deficiency ( OR=2.02, 95% CI: 1.17-3.50), periodontitis ( OR=4.51, 95% CI: 1.76-11.55) were the main risk factors for DR. Intensive blood pressure intervention ( RR=0.78, 95% CI: 0.65-0.94), dietary control ( OR=0.64, 95% CI: 0.47-0.89) and moderate intensity physical activity ( RR=0.76, 95% CI: 0.59-0.97) yielded significant protective associations with DR. Conclusions:Intensive blood pressure glycemic control, and a healthy lifestyle pattern could reduce the risk of DR. This study provides the evidence to identify high-risk populations and recommends rational treatment options and healthy living interventions.