OBJECTIVE:To systematically evaluate the efficacy of transcranial direct current stimulation on the motor function of patients with Parkinson's disease,and to compare the efficacy of transcranial direct current stimulation at different targets on the motor function of patients with Parkinson's disease,so as to provide a theoretical basis for the target selection of transcranial direct current stimulation in clinical practice. METHODS:Cochrane Library,PubMed,Web of Science,CNKI,VIP,WanFang Data were retrieved for randomized controlled trials on the improvement of motor function in patients with Parkinson's disease by transcranial direct current stimulation published from the database inception to January 2023.The keywords were"Parkinson,transcranial direct current stimulation"in English and Chinese.The quality of the included studies was evaluated using the Cochrane 5.1.0 risk of bias assessment tool and the PEDro scale.Meta-analysis of outcome indicators was performed using RevMan 5.4 and Stata 17.0 software. RESULTS:Fifteen randomized controlled trials were finally included,and the PEDro scale showed that all were high-quality or very high-quality studies.Meta-analysis showed that transcranial direct current stimulation significantly improved Unified-Parkinson Disease Rating Scale part III score[mean difference(MD)=-2.49,95%confidence interval(CI):-4.42 to-0.55,P<0.05),step frequency score(MD=0.07,95%CI:0.03-0.11,P<0.05)and step speed score(MD=0.02,95%CI:0.00-0.05,P<0.05),but not for Berg Balance Scale scores(MD=2.57,95%CI:-0.74 to 5.87,P>0.05).Network Meta-analysis probability ranking:In terms of Unified-Parkinson Disease Rating Scale part III scores,the probability ranking results of target stimulation efficacy were dorsal lateral prefrontal cortex(52.4%)>primary motor cortex(45.8%)>central point of the brain(1.8%)>conventional rehabilitation(0%);in terms of gait frequency scores,the probability probability ranking results of target stimulation efficacy were cerebellum(50.1%)>central point of the brain(45.8%)>dorsal lateral prefrontal cortex(3.9%)>primary motor cortex(0.2%)>conventional rehabilitation(0%);in terms of gait speed scores,the probability ranking results of target stimulation efficacy were cerebellum(64.8%)>dorsal lateral prefrontal cortex(23.8%)>central point of the brain(9.4%)>primary motor cortex(1.7%)>conventional rehabilitation(0.4%);in terms of Berg Balance Scale scores,the probability ranking results of target stimulation efficacy were cerebellum(77.4%)>dorsal lateral prefrontal cortex(20.7%)>central point of the brain(0.7%)>conventional rehabilitation(0.2%). CONCLUSION:Transcranial direct current stimulation significantly improves motor function of patients with Parkinson's disease,with better motor coordination in the dorsolateral prefrontal cortex and better walking and balance in the cerebellum.

Chinese materia medica and its compound formulas have the characteristics of multi-component,multi-target,and multi pathway effects,and have unique advantages in preventing and treating complex diseases.Network pharmacology explains disease patterns and drug mechanisms from the perspective of complex biological networks,and explores the pharmacological substance basis and target of Chinese medicine.This article summarized the application of network pharmacology from the aspects of biological basis of TCM syndrome,the substance basis and pharmacological mechanism of TCM,compatibility theory of TCM compound formulas,etc.,with the purpose to provide a reference for the research and application of network pharmacology in TCM.

Objective To explore the effect of etomidate-propofol mixture anaesthesia in painless gastrointestinal endoscopy.Methods Eighty-two patients who underwent painless gastrointestinal endoscopy from September 2023 to November 2023 were divided into etomidate-propofol mixture group(observation group,n=41)and propofol group(control group,n=41)by using the random number table method.Morphine-benzedrine group(MBG)scores were recorded 30 min before the examination and before leaving the recovery room in both groups.Percutaneous arterial oxygen saturation(SpO2),heart rate(HR)and mean arterial pressure(MAP)were noted at anesthesia induction(T0),before entering the endoscope(T1),5 min after anesthesia induction(T2),and awakening(T3).Gastrointestinal endoscopy time,awakening time,recovery room stay time,total propofol consumption,and adverse reactions were also documented.Results MBG scores in both groups significantly increased before leaving the recovery room compared to 30 min before the examination,the observation group had lower MBG scores before leaving the recovery room in comparison with the control group,there were statistically significant(P＜0.05).From T1 to T3,MAP,SpO2,HR were higher in the observation group than those in the control group,there were statistically significant(P＜0.05).The observation group had shorter awakening time and recovery room stay time,there were statistically significant(P＜0.05).The observation group had lower total propofol consumption,there was statistically significant(P＜0.05).The observation group also exhibited a lower incidence of hypotension,hypoxemia,and injection pain,there were statistically significant(P＜0.05),with no statistically significant difference in the incidence of other adverse reactions(P＞0.05).Conclusion Etomidate-propofol combination anesthesia can reduce postoperative MBG scores in painless gastrointestinal endoscopy,contributing to a decreased risk of potential propofol addiction and abuse.Additionally,it stabilizes circulatory and respiratory functions,reduces adverse reactions rate,and shortens awakening time and recovery room stay time.Its application is worthy of further promotion.

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

Objective:To preliminarily analyze the expression of angiotensin-converting enzyme 2 (ACE2) and to investigate its potential regulatory mechanism in chronic rhinosinusitis with nasal polyps (CRSwNP).Methods:Patients underwent nasal endoscopic surgery in the Third Affiliated Hospital of Sun Yat-sen University from February 2020 to May 2021 were selected, including 17 males and 6 females, aging from 23 to 66 years old. Expression of ACE2 was evaluated via immunohistochemical staining in controls with non-chronic rhinosinusitis, non-eosinophilic CRSwNP (non-ECRSwNP), and eosinophilic CRSwNP (ECRSwNP) tissue, respectively. Correlations between ACE2 and the indicated Th1/Th2-related cytokines (IFN-γ, IL-4, IL-5, IL-13, IL-25, IL-33, TSLP and periostin) were analyzed based on GSE72713 dataset. Protein-protein interaction (PPI) network was constructed via string database, immune infiltration of GSE72713 dataset was evaluated using cibersort algorithm. ACE2 was comprehensively analyzed by microRNA regulatory network, gene set enrichment analysis (GSEA) and pharmacological analysis. Statistical analysis was performed using GraphPad 7.0 and SPSS 20.0 software.Results:ACE2 was up-regulated in non-ECRSwNP compared with ECRSwNP. Microarray analysis showed that ACE2 was positively correlated with IFN-γ while inversely correlated with IL-5, IL-13 and periostin significantly. Analysis of immune infiltration suggested that ACE2 expression correlated positively with the number of M1 macrophage while negatively with M2 macrophage. GSEA demonstrated that interferon-related signaling pathways were up-regulated in non-ECRSwNP, and miRNA-200B/miRNA-200C/miRNA-429 pathways targeting ACE2 were enriched in ECRSwNP. Results of pharmacological analysis indicated that ampicillin was able to promote the expression of ACE2 whereas acetaminophen could down regulated the expression of ACE2.Conclusion:Expression pattern of ACE2 is varied in non-ECRSwNP and ECRSwNP, which may be related to the different infiltration of indicated cytokines and different regulatory pathways of miRNA.

Since its birth in the early 1990s, metabolic engineering technology has gone 30 years rapid development. As one of the preferred chassis for metabolic engineering, S. cerevisiae cells have been engineered into microbial cell factories for the production of a variety of bulk chemicals and novel high value-added bioactive compounds. In recent years, synthetic biology, bioinformatics, machine learning and other technologies have also greatly contributed to the technological development and applications of metabolic engineering. This review summarizes the important technological development for metabolic engineering of S. cerevisiae in the past 30 years. Firstly, classical metabolic engineering tools and strategies were reviewed, followed by reviewing systems metabolic engineering and synthetic biology driven metabolic engineering approaches. The review is concluded with discussing future perspectives for metabolic engineering of S. cerevisiae in the light of state-of-the-art technological development.
Computational Biology ; Metabolic Engineering ; Saccharomyces cerevisiae/genetics* ; Synthetic Biology

Although DNA 5-hydroxymethylcytosine (5hmC) is recognized as an important epige-netic mark in cancer, its precise role in lymph node metastasis remains elusive. In this study, we investigated how 5hmC associates with lymph node metastasis in breast cancer. Accompanying with high expression of TET1 and TET2 proteins, large numbers of genes in the metastasis-positive pri-mary tumors exhibit higher 5hmC levels than those in the metastasis-negative primary tumors. In contrast, the TET protein expression and DNA 5hmC decrease significantly within the metastatic lesions in the lymph nodes compared to those in their matched primary tumors. Through genome-wide analysis of 8 sets of primary tumors, we identified 100 high-confidence metastasis-associated 5hmC signatures, and it is found that increased levels of DNA 5hmC and gene expression of MAP7D1 associate with high risk of lymph node metastasis. Furthermore, we demonstrate that MAP7D1, regulated by TET1, promotes tumor growth and metastasis. In conclusion, the dynamic 5hmC profiles during lymph node metastasis suggest a link between DNA 5hmC and lymph node metastasis. Meanwhile, the role of MAP7D1 in breast cancer progression suggests that the metastasis-associated 5hmC signatures are potential biomarkers to predict the risk for lymph node metastasis, which may serve as diagnostic and therapeutic targets for metastatic breast cancer.

Oral squamous cell carcinoma (OSCC) is a common cancer that develops from oral epithelial cells, it has a high incidence, mortality and teratogenic rate, which poses a serious threat to people′s life and health.The Hippo signaling pathway plays a key role in tumorigenesis, regulation of stem cell homeostasis, tissue regeneration, and organ size control. In OSCC, activation of Hippo signaling pathway can inhibit malignant biological behavior, epithelial mesenchymal transformation and distant metastasis of tumors, and improve the survival rate of patients. Considering the importance of the Hippo signaling pathway in the development of cancer, this paper summarized the composition and regulatory mechanism of Hippo pathway, elaborated the role of Hippo signaling pathway in the occurrence and development of OSCC.At the same time, make a simple generalization about the potential therapeutic approaches and strategies to reduce the risk of drug resistance for OSCC patients targeting this pathway.

Objective:To investigate the expression and cellular provenance of interleukin 17A (IL-17A) in non-eosinophilic chronic rhinosinusitis with nasal polyps (nECRSwNP), and to analyze the possible reasons for its different expression.Methods:Samples were collected from 14 patients with eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) and 28 patients with nECRSwNP, who underwent functional endoscopic sinus surgery in the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to May 2018, including 33 males and 9 females, with the age ranging from 18 to 65 years old. Enzyme linked immune sorbent assay (ELISA) and flow cytometry were used to investigate the expression and cellular origins of IL-17A in the nasal tissue of ECRSwNP and nECRSwNP groups. Then the difference of quantity and differentiation ability of the major cells producing IL-17A between ECRSwNP and nECRSwNP groups were analyzed by flow cytometry. Finally, the expressions of IL-6, transforming growth factor-β(TGF-β), and IL-23, which were considered as the important factors in promoting Th17/Tc17 differentiation in CRSwNP and their correlation with IL-17A, were analyzed by ELISA. Statistical analysis was performed using IBM SPSS 20.Results:The IL-17A protein levels and IL-17A +lymphocyte percentages were higher in nECRSwNP group compared with that of the ECRSwNP group (158.56 (167.76) pg/ml ( M( QR)) vs. 9.42 (11.33) pg/ml, 10.21%±1.54% ( ± s) vs. 3.93%±0.80%, Z=2.95, t=3.62, all P<0.01). Tc17 cells (CD8 +T cells producing IL-17A) and Th17 cells (CD4 +T cells producing IL-17A) were major IL-17A producers in both ECRSwNP and nECRSwNP group. Further analysis revealed that there was no significant difference in quantity of CD8 +and CD4 +T cells between ECRSwNP and nECRSwNP group, but the differentiation ability about CD8 +and CD4 +T cells differentiating into Tc17 and Th17 in nECRSwNP group was stronger than that in ECRSwNP. The high expressions of IL-6 and TGF-β, which were considered as the important factors in promoting Th17/Tc17 differentiation were also found in nECRSwNP group compared with ECRSwNP (56.07 (234.25) pg/ml vs. 8.27 (12.51) pg/ml, (5.44±0.34) pg/ml vs. (4.17±0.22) pg/ml, Z=2.426, t=2.29, all P<0.05). But the difference in expression of IL-23 was not significant difference between the two groups. Moreover, the expression of IL-17A showed significantly positive correlation with IL-6 ( r=0.615, P=0.009). No positive correlation between IL-17A and TGF-β or IL-23 was observed. Conclusions:The expression of IL-17A in nasal mucosa of nECRSwNP patients is significantly higher than that of ECRSwNP, which is due to the increase of expression and differentiation of Tc17/Th17 cells. IL-17A shows positive correlation with IL-6 in CRSwNP, which is the important factor in promoting Th17/Tc17 differentiation.

Objective To investigate the effect of sarcopenia on the skeletal muscle and cardiac function in elderly patients with chronic heart failure (CHF).Methods Sixty patients with CHF and sarcopenia and 60 sex and age-matched CHF patients without sarcopenia were enrolled from September 2014 to December 2015.The skeletal mass was evaluated by fat-free mass index (FFMI) and muscle function was evaluated by gait speed (GS),hand strength (HS) and the simple physical performance battery (SPPB).The cardiac function was accessed by a 6-min walk distance (6-MWD) and left ventricular ejection fraction (LVEF).Furthermore,the serum inflammation cytokines IL-6,TNF-α,and skeletal muscle biomarker C 1q were measured.Results The CHF patients with sarcopenia had lower values for skeletal muscle mass:FFMI [(17.68±0.74) vs.(18.34±0.54)kg/m2,F=33.696,P＜0.05] and lower muscle function:HS [(17.26±4.20)vs.(28.85±6.43)kg,F=136.54,P＜0.05],GS [(0.65±0.11) vs.(0.90±0.10)m/s,F=-12.922,P＜0.05],SPPB [(6.45±2.07) vs.(7.65± 1.76),t=-3.452,P＜0.05].And the cardiac function decreased significantly in patients with sarcopenia:6-MWD [(253.76 ± 72.62) vs.(340.91 ± 55.78)m,F=54.350,P＜0.05],LVEF [(39.12 ± 7.02)vs.(43.83±5.81)％,t=16.060,P＜0.05].Serum IL-6/TNF-α/C1q levels were significantly elevated:IL-6[(14.12± 1.40) vs.(13.46±1.06) ng/L,F=8.513,P＜0.05],TNF-α [(443.43±28.06) vs.(299.37±21.53)ng/L,t=31.556,P＜0.05],C1q[(578.92±23.63) vs.(504.1 1±41.77)ng/L,F=145.78,P＜0.05].Conclusion The CHF patients with sarcopenia present less skeletal muscle mass,poorer skeletal function and reduced cardiac function,and higher inflammation levels.