Effectiveness and brain mechanism of multi-target transcranial alternating current stimulation (tACS) on motor learning in stroke patients: study protocol for a randomized controlled trial.

BACKGROUND: Transcranial alternating current stimulation (tACS) has proven to be an effective treatment for improving cognition, a crucial factor in motor learning. However, current studies are predominantly focused on the motor cortex, and the potential brain mechanisms responsible for the therapeutic effects are still unclear. Given the interconnected nature of motor learning within the brain network, we have proposed a novel approach known as multi-target tACS. This study aims to ascertain whether multi-target tACS is more effective than single-target stimulation in stroke patients and to further explore the potential underlying brain mechanisms by using techniques such as transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI). METHODS: This study employs a double-blind, sham-controlled, randomized controlled trial design with a 2-week intervention period. Both participants and outcome assessors will remain unaware of treatment allocation throughout the study. Thirty-nine stroke patients will be recruited and randomized into three distinct groups, including the sham tACS group (SS group), the single-target tACS group (ST group), and the multi-target tACS group (MT group), at a 1:1:1 ratio. The primary outcomes are series reaction time tests (SRTTs) combined with electroencephalograms (EEGs). The secondary outcomes include motor evoked potential (MEP), central motor conduction time (CMCT), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), magnetic resonance imaging (MRI), Box and Block Test (BBT), and blood sample RNA sequencing. The tACS interventions for all three groups will be administered over a 2-week period, with outcome assessments conducted at baseline (T0) and 1 day (T1), 7 days (T2), and 14 days (T3) of the intervention phase. DISCUSSION: The study's findings will determine the potential of 40-Hz tACS to improve motor learning in stroke patients. Additionally, it will compare the effectiveness of multi-target and single-target approaches, shedding light on their respective improvement effects. Through the utilization of techniques such as TMS and MRI, the study aims to uncover the underlying brain mechanisms responsible for the therapeutic impact. Furthermore, the intervention has the potential to facilitate motor learning efficiency, thereby contributing to the advancement of future stroke rehabilitation treatment. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300073465. Registered on 11 July 2023.

Artificial Intelligence to Diagnose Tibial Plateau Fractures: An Intelligent Assistant for Orthopedic Physicians.

OBJECTIVE: To explore a new artificial intelligence (AI)-aided method to assist the clinical diagnosis of tibial plateau fractures (TPFs) and further measure its validity and feasibility. METHODS: A total of 542 X-rays of TPFs were collected as a reference database. An AI algorithm (RetinaNet) was trained to analyze and detect TPF on the X-rays. The ability of the AI algorithm was determined by indexes such as detection accuracy and time taken for analysis. The algorithm performance was also compared with orthopedic physicians. RESULTS: The AI algorithm showed a detection accuracy of 0.91 for the identification of TPF, which was similar to the performance of orthopedic physicians (0.92±0.03). The average time spent for analysis of the AI was 0.56 s, which was 16 times faster than human performance (8.44±3.26 s). CONCLUSION: The AI algorithm is a valid and efficient method for the clinical diagnosis of TPF. It can be a useful assistant for orthopedic physicians, which largely promotes clinical workflow and further guarantees the health and security of patients.

[Effects of fire intensity on leaf functional traits and functional diversity of Larix gmelinii community]. / ç«çƒ§å¼ºåº¦å¯¹å ´å®‰è½å¶æ¾ç¾¤è½å¶ç‰‡åŠŸèƒ½æ€§çŠ¶åŠåŠŸèƒ½å¤šæ ·æ€§çš„å½±å“.

Fire is an important ecological factor in boreal coniferous forest, which directly affects plant taxonomic and functional diversity and consequently forest succession. We analyzed the changes of soil nutrient contents, leaf functional traits, taxonomic and functional diversity of a Larix gmelinii community under different fire intensity levels (low, medium, heavy). The forest stand had been naturally recovered for 12 years in Yakeshi area. The results showed that fire significantly reduced soil total nitrogen content, but did not affect soil total phosphorus content. Low and medium fire intensities could maintain higher species diversity and functional diversity of the community. Medium fire disturbance significantly increased species diversity of the community, with maximum species richness index, Shannon index, Simpson index and Pielou evenness index. Fire disturbance reduced functional richness and functional divergence of the community, which were the largest in medium and low fire intensity respectively (except unburned). Functional evenness and Rao qua-dratic entropy index increased after forest fire disturbance, and the largest was in the low intensity burned area. With the increases of fire intensity, leaf dry matter content, leaf tissue density and leaf total phosphorus content showed a significantly increased trend, while specific leaf area, leaf water content, leaf total nitrogen content and leaf N:P showed the trend unburned ＞ medium fire ＞ low fire ＞ heavy fire, leaf thickness increased first and then decreased. Fire intensity had significant effects on leaf functional traits and functional diversity of forest community. Moderate fire distur-bance could promote forest restoration.

Comparison and analysis on the serum-binding characteristics of aspirin-zinc complex and aspirin.

This study was designed to compare the protein-binding characteristics of aspirin-zinc complex (AZN) with those of aspirin itself. AZN was synthesized and interacted with a model transport protein, human serum albumin (HSA). Three-dimensional fluorescence, ultraviolet-visible and circular dichroism (CD) spectra were used to characterize the interaction of AZN with HSA under physiological conditions. The interaction mechanism was explored using a fluorescence quenching method and thermodynamic calculation. The binding site and binding locality of AZN on HSA were demonstrated using a fluorescence probe technique and Förster non-radiation energy transfer theory. Synchronous fluorescence and CD spectra were employed to reveal the effect of AZN on the native conformation of the protein. The HSA-binding results for AZN were compared with those for aspirin under consistent experimental conditions, and indicated that aspirin acts as a guide in AZN when binding to Sudlow's site I, in subdomain IIA of the HSA molecule. Moreover, compared with aspirin, AZN showed greater observed binding constants with, but smaller changes in the α-helicity of, HSA, which proved that AZN might be easier to transport and have less toxicity in vivo.

Outcomes of simple saline-coupled bipolar electrocautery for hepatic resection.

AIM: To evaluate the application of bipolar coagulation (BIP) in hepatectomy by comparing the efficacy of BIP alone, cavitron ultrasonic surgical aspirator (CUSA) + BIP and conventional clamp crushing (CLAMP). METHODS: Based on our database of patient records, a total of 380 consecutive patients who underwent hepatectomy at our hospital were retrospectively studied for the efficacy of BIP alone, CUSA + BIP and CLAMP. Of all the patients, 75 received saline-coupled BIP (Group A), 53 received CUSA + BIP (Group B), and 252 received CLAMP (Group C). The pre-, mid-, and postoperative clinical manifestations were compared, and the effects of those maneuvers were evaluated. RESULTS: There was no obvious difference among the preoperative indexes between the different groups. The operative time was longer in Groups A and B than in Group C (P < 0.001 for both). The amount of bleeding and the rate of transfusion during the operation were significantly higher in Group C than in Groups A and B (P < 0.001 for all). The incidence of postoperative complications in Group C (46.43%) was higher than that in Groups A (30.67%, P = 0.015) and B (28.30%, P = 0.016). The patients' liver function recovery and postoperative hospital stay were not significantly different. BIP could decrease intraoperative hemorrhage and postoperative complications compared to CLAMP. CONCLUSION: Simple saline-coupled BIP should be considered a safe and reliable technique for liver resection to decrease intraoperative hemorrhage and postoperative complications.

Preventive and therapeutic effects of adenanthin on experimental autoimmune encephalomyelitis by inhibiting NF-κB signaling.

Adenanthin, a diterpenoid isolated from the leaves of Isodon adenanthus, has been reported to possess antileukemic activity through targeting peroxiredoxin I/II. However, its other potential activities remain to be explored. Using myelin oligodendrocyte glycoprotein (MOG)35-55-induced experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, we report in this study that adenanthin exerts efficaciously preventive and therapeutic effects on EAE accompanied by significant restriction of infiltration of inflammatory cells and demyelination in CNS. Adenanthin-presented immunomodulatory effects on EAE are correlated with suppressed proliferation of MOG35-55-reactive T cells, decreased Th1 and Th17 cells, increased regulatory T cell populations, decreased production of serum proinflammatory cytokines, and reduced stimulatory capacity of APCs, which might be mediated by its inhibitory action on NF-κB signaling pathway. Our results propose that, as a novel NF-κB inhibitor, adenanthin has potent immunomodulatory activity for the treatment of multiple sclerosis and possibly other autoimmune disorders.

Dermal mesenchymal stem cells (DMSCs) inhibit skin-homing CD8+ T cell activity, a determining factor of vitiligo patients' autologous melanocytes transplantation efficiency.

We here investigated the efficiency of autologous melanocyte transplantation of 23 vitiligo patients by focusing on perilesional skin homing CD8+ T lymphocytes, and studied the potential effect of dermal mesenchymal stem cells (DMSCs) on CD8+ T cell activities in vitro. Out of 23 patients with the autologous melanocyte transplantation, 12 patients (52.17%) had an excellent re-pigmentation, 6 patients (26.09%) had a good re-pigmentation, 5 patients (21.74%) had a fair or poor re-pigmentation. CD8+ T cells infiltrating was observed in the perilesional vitiligo area of all patients. Importantly, the efficiency of the transplantation was closely associated with skin-homing CD8+ T cell activities. The patients with high number of perilesional CD8+ T cells or high level of cytokines/chemokines were associated with poor re-pigmentation efficiency. For in-vitro experiments, we successfully isolated and characterized human DMSCs and skin-homing CD8+ T cells. We established DMSCs and CD8+ T cell co-culture system, where DMSCs possessed significant inhibitory effects against skin homing CD8+ T lymphocytes. DMSCs inhibited CD8+ T cells proliferation, induced them apoptosis and regulated their cytokines/chemokines production. Our results suggest that vitiligo patients' autologous melanocytes transplantation efficiency might be predicted by perilesional skin-homing CD8+ T cell activities, and DMSCs might be used as auxiliary agent to improve transplantation efficacy.

Expression of proteasome immunosubunit in labial glands of patients with primary Sjogren's syndrome / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the expression of proteasome immunosubunit low molecular weight polypeptide (LMP)2 and LMP7 in labial glands of patients with primary Sjogren's syndrome patients, and thus explore their role in the diagnosis, differential diagnosis and pathogenesis of primary Sjogren's syndrome (pSS).</p><p><b>METHODS</b>Labial specimens were collected from 40 patients with pSS, 15 patients with connective tissue diseases other than pSS, and 9 healthy controls. The expressions of LMP2 and LMP7 in labial specimens were determined using immunohistochemical approaches and analyzed using semi-quantitative methods. The positive rate of acinar was calculated. After the square arcsine transformation of data, the differences of the positive rate in acinar between LMP2 and LMP7 were compared among three groups. Spearman's rank correlation coefficient was used for analyzing the correlation of clinical manifestations with LMP2 and LMP7 expressions.</p><p><b>RESULTS</b>The expressions of LMP2 and LMP7 within the acinar and ductal epithelial cells were confirmed. Although the LMP2 expression in labial specimens was not significantly different among three groups(P=0.369), the expression of LMP7 was significantly higher in pSS patients compared with patients with connective tissue disease and healthy controls (P<0.01). Only in pSS group, LMP7 was found to be with higher positive rate in acinar than LMP2 (P<0.01). No significant correlation was found between LMP2/LMP7 and clinical manifestations (P>0.05).</p><p><b>CONCLUSION</b>In patients with pSS, the expression of LMP7 (but not LMP2) is up-regulated in labial gland, indicating these two proteins have different genetic regulation mechanisms.</p>

Numerical investigation of regurgitation phenomena in pulmonary arteries of Tetralogy of Fallot patients after repair.

Pulmonary regurgitation is a very common phenomenon in pulmonary arteries after repair of patients of Tetralogy of Fallot (TOF) which is the most common complex congenital heart diseases. The aim of this study is to use numerical approaches to simulate flow variations in pulmonary artery after repair of patients of TOF. We analyze the flow patterns in an in-vitro bifurcation pulmonary artery and consider effects of various regurgitation fractions (RF or b/f) in left pulmonary artery (LPA) and right pulmonary artery (RPA). We not only observe the variation of flow patterns, but also analyze the results of b/f and net volumetric flow rates in LPA and RPA. In general, the b/f of LPA is higher than RPA in the measured data provided by phase-contrast magnetic resonance imaging (PC-MRI). We validate the result using numerical approaches to analyze the flow patterns in pulmonary artery in this study. The results will be useful for medical doctors when they perform operations for TOF patients.

T-2 toxin-induced apoptosis involving Fas, p53, Bcl-xL, Bcl-2, Bax and caspase-3 signaling pathways in human chondrocytes.

OBJECTIVE: To investigate the effects of T-2 toxin on expressions of Fas, p53, Bcl-xL, Bcl-2, Bax and caspase-3 on human chondrocytes. METHODS: Human chondrocytes were treated with T-2 toxin (1-20 ng/ml) for 5 d. Fas, p53 and other apoptosis-related proteins such as Bax, Bcl-2, Bcl-xL, caspase-3 were determined by Western blot analysis and their mRNA expressions were determined by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Increases in Fas, p53 and the pro-apoptotic factor Bax protein and mRNA expressions and a decrease of the anti-apoptotic factor Bcl-xL were observed in a dose-dependent manner after exposures to 1-20 ng/ml T-2 toxin, while the expression of the anti-apoptotic factor Bcl-2 was unchanged. Meanwhile, T-2 toxin could also up-regulate the expressions of both pro-caspase-3 and caspase-3 in a dose-dependent manner. CONCLUSION: These data suggest a possible underlying molecular mechanism for T-2 toxin to induce the apoptosis signaling pathway in human chondrocytes by regulation of apoptosis-related proteins.

[Clinical significance of detection of tumor suppressor genes aberrant methylation in cervical carcinoma tissue].

OBJECTIVE: To investigate the change of aberrant methylation of p16, CDH, RASSF1A and TIMP3 in cervical carcinoma and their significance in cervical carcinoma. METHODS: Using the bisulfite-modification technique and methylation-specific PCR (MSP), we examined the aberrant promoter hypermethylation patterns of 4 tumor suppressor genes (p16, CDH1, RASSF1A, TIMP3) in 140 samples of cervical intraepithelial neoplasia (CINI, n = 40), CINII-III (n = 40), cervical carcinomas (CC, n = 40), and normal cervical tissue as a control group (n = 20). RESULTS: (1) Methylation was completely absent in control tissues. (2) Significant differences between CINII-III group and CINI group were detected for p16 and CDH1 (22% vs 2%, P < 0.05; 35% vs 5%, P < 0.05), while there were no significant differences between the two groups for RASSF1A and TIMP3 (12% vs 2%, P > 0.05; 15% vs 2%, P > 0.05). (3) The presence of methylation of p16 (40%), CDH1 (58%), RASSF1A (20%) and TIMP3 (35%) in CC were higher than the corresponding CINII-III group, but with no significant differences (P > 0.05). (4) Significant differences between CC and CINIfor p16, CDH1, RASSF1A and TIMP3 genes (P < 0.05) were observed. (5) Methylation for at least one gene was a frequent event. These figures in CC 90% (36/40) were significantly different from CINII-III 55% (22/40; P < 0.05). In comparison between CINI8% (3/40) and CC and CINII-III, these figures were significantly different (P < 0.05). CONCLUSIONS: Among the four genes, p16, CDH, RASSF1A and TIMP3, there is a significant trend for increased methylation with increasing degree of histopathological change. It suggests that the aberrant methylation of tumor suppressor genes plays a role during cervical cancer development. This may help identify women at increased risk for or cancer development and progression.

[Protective effect of selenium against T-2 toxin-induced inhibition of chondrocyte aggrecan and collagen II synthesis].

OBJECTIVE: To study the inhibitory effect of T-2 toxin on the expression of aggrecan and collagen II in chondrocytes and the protection of selenium against this effect. METHODS: Human chondrocytes cultured in vitro were treated with T-2 toxin at different concentrations for varied time periods (1-5 days), and the cell viability was measured by MTT assay. Aggrecan expression was detected by toluidine blue staining and collagen II expression by immunostaining using monoclonal antibody of collagen. Aggrecan and collagen II mRNA expressions were measured by semiquantitative RT-PCR. RESULTS: T-2 toxin dose- and time-dependently affected chondrocyte viability within the concentration range of 0.001-2 mg/L, the prolonged treatment time further enhanced the dose dependence of the inhibitory effect. T-2 toxin lowered aggrecan and collagen II synthesis in the chondrocytes and reduced their mRNA expressions. Selenium could partly attenuate the inhibitory effects of T-2 toxin on aggrecan mRNA expression, but showed no such effect against T-2-induced collagen II expression. CONCLUSION: T-2 toxin can obviously inhibit aggrecan and collagen II synthesis in human chondrocytes, and selenium can partly antagonize the inhibitory effects of T-2 toxin on aggrecan.

[Role of matrix metalloproteinase-2,9 and their inhibitors in premature rupture of membranes].

OBJECTIVE: To investigate the role of matrix metalloproteinase-2,9 (MMP-2, MMP-9) and tissue inhibitor of matrix metalloproteinases-2,1 (TIMP-2, TIMP-1) in human amniochorionic membrane. METHODS: Amniochorionic membranes were collected from the following groups of women: (1) women with spontaneous premature rupture of membrane (PROM) before onset of labor (PROM group, n = 8), (2) Women with term labor after vaginal delivery (vaginal delivery group, n = 8), (3) Women undergoing elective cesarean section (C-section group, n = 8). Messenger ribonucleic acid expression for MMP-2, MMP-9, and their specific inhibitors TIMP-2 and TIMP-1 were studied with reverse transcriptase polymerase chain reaction. RESULTS: (1) MMP-2 level in PROM group was 0.849 +/- 0.037; in vaginal delivery group 0.327 +/- 0.023; in C-section group 0.307 +/- 0.028. Expression in PROM group was highest, with significant difference compared with the other groups (P < 0.05). Its expression in vaginal delivery group and C-section group had no significant difference (P > 0.05). (2) MMP-9 level in PROM group was 0.026 +/- 0.004; in vaginal delivery group 0.008 +/- 0.001, with significant difference between the two groups (P < 0.05), while the expression was absent in C-section group. (3) TIMP-2 level in PROM group was 0.420 +/- 0.122; in vaginal delivery group 0.730 +/- 0.148; in C-section group 0.885 +/- 0.065. The expression in PROM group was significantly lower than in vaginal delivery group and C-section group (P < 0.05). And it was significantly lower in vaginal delivery group than in C-section group (P < 0.05). (4)TIMP-1 level in PROM group was 0.442 +/- 0.020; in vaginal delivery group 0.431 +/- 0.016; in C-section group 0.427 +/- 0.011. The expression in three groups had no significant difference (P > 0.05). CONCLUSIONS: In PROM group, the expression of MMP-2, MMP-9 and their inhibitors TIMP-2, TIMP-1 is imbalanced, leading to increased extracellular matrix degradation, and weakening of the fetal membranes, and eventually premature rupture of the membranes.

[Mapping QTLs of soybean root weight with RIL population NJRIKY].

The recombinant inbred line (RIL) population, NJRIKY with 184 families derived from a cross Kefeng No.1 x Nannong1138-2 was used in mapping QTLs of root weight of soybean. Based on the linkage map constructed by Wang, with the software Cartographer V. 1.21 of the composite interval mapping procedure, three QTLs of root weight were mapped on N3-B1 and N6-C2 linkage group. The left telomere distance of rw1 was 66.31cM on N3-B1 linkage group, and those of rw2 and rw3 were 169.91cM and 179.71 cM, respectively, on N6-C2 linkage group. The former was located in A520T approximately ACCCAGO5 and the latter were overlapped with OPW13 and ACGCATO6, respectively. Their LOD values were 10.34,4.01 and 3.15, respectively. The QTLs of the root weight explained 26.3%,9.2% and 6.8% of the total variation, and their additive effects were -0.514,-0.303 and -0.260, respectively.