Cervical lymph node metastasis as the first symptom of combined anaplastic thyroid carcinoma (squamous cell carcinoma) and follicular carcinoma: a case report.

BACKGROUND: Anaplastic thyroid carcinoma(ATC) is a rare pathological type of thyroid malignancy. Primary squamous cell carcinoma of thyroid(PSCCT) is now considered as a subtype of ATC, hereinafter referred to as ATC-SCC subtype. ATC-SCC subtype combined with follicular thyroid carcinoma is exceedingly rare, with fewer cases reported. The ATC-SCC subtype is a highly invasive tumor with a poor prognosis for patients after metastasis occurs, and current treatment of this type of tumor is tricky. CASE PRESENTATION: A 68-year-old female patient presented with a gradually growing swelling of right cervical region. Comprehensive auxiliary examinations and postoperative pathology confirmed the diagnosis of ATC-SCC subtype with follicular thyroid carcinoma, and the metastasis squamous cell carcinoma of the right cervical lymph nodes originates from ATC-SCC subtype. The patient received chemoradiotherapy postoperative. However, the residual cervical lymph nodes metastasis with squamous cell carcinoma still infiltrated surrounding structures in the neck extensively after palliative resection. The patient died 7 months after surgery. CONCLUSION: Our case highlights that cervical lymph node metastasis may be a significant factor in the poor prognosis of ATC-SCC subtype. This malignancy should be detected and treated early.

Alpha-Synuclein Interaction with UBL3 Is Upregulated by Microsomal Glutathione S-Transferase 3, Leading to Increased Extracellular Transport of the Alpha-Synuclein under Oxidative Stress.

Aberrant aggregation of misfolded alpha-synuclein (α-syn), a major pathological hallmark of related neurodegenerative diseases such as Parkinson's disease (PD), can translocate between cells. Ubiquitin-like 3 (UBL3) is a membrane-anchored ubiquitin-fold protein and post-translational modifier. UBL3 promotes protein sorting into small extracellular vesicles (sEVs) and thereby mediates intercellular communication. Our recent studies have shown that α-syn interacts with UBL3 and that this interaction is downregulated after silencing microsomal glutathione S-transferase 3 (MGST3). However, how MGST3 regulates the interaction of α-syn and UBL3 remains unclear. In the present study, we further explored this by overexpressing MGST3. In the split Gaussia luciferase complementation assay, we found that the interaction between α-syn and UBL3 was upregulated by MGST3. While Western blot and RT-qPCR analyses showed that silencing or overexpression of MGST3 did not significantly alter the expression of α-syn and UBL3, the immunocytochemical staining analysis indicated that MGST3 increased the co-localization of α-syn and UBL3. We suggested roles for the anti-oxidative stress function of MGST3 and found that the effect of MGST3 overexpression on the interaction between α-syn with UBL3 was significantly rescued under excess oxidative stress and promoted intracellular α-syn to extracellular transport. In conclusion, our results demonstrate that MGST3 upregulates the interaction between α-syn with UBL3 and promotes the interaction to translocate intracellular α-syn to the extracellular. Overall, our findings provide new insights and ideas for promoting the modulation of UBL3 as a therapeutic agent for the treatment of synucleinopathy-associated neurodegenerative diseases.

Rapid Defect Engineering in FeCoNi/FeAl2O4 Hybrid for Enhanced Oxygen Evolution Catalysis: A Pathway to High-Performance Electrocatalysts.

Rational modulation of surface reconstruction in the oxygen evolution reaction (OER) utilizing defect engineering to form efficient catalytic activity centers is a topical interest in the field of catalysis. The introduction of point defects has been demonstrated to be an effective strategy to regulate the electronic configuration of electrocatalysts, but the influence of more complex planar defects (e.g., twins and stacking faults), on their intrinsic activity is still not fully understood. This study harnesses ultrasonic cavitation for rapid and controlled introduction of different types of defects in the FeCoNi/FeAl2O4 hybrid coating, optimizing OER catalytic activity. Theoretical calculations and experiments demonstrate that the different defects optimize the coordination environment and facilitate the activation of surface reconstruction into true catalytic activity centers at lower potentials. Moreover, it demonstrates exceptional durability, maintaining stable oxygen production at a high current density of 300 mA cm-2 for over 120 hours. This work not only presents a novel pathway for designing advanced electrocatalysts but also deepens our understanding of defect-engineered catalytic mechanisms, showcasing the potential for rapid and efficient enhancement of electrocatalytic performance.

CRISPR-based DNA methylation editing of NNT rescues the cisplatin resistance of lung cancer cells by reducing autophagy.

Cisplatin is recommended as a first-line chemotherapeutic agent against advanced non-small cell lung cancer (NSCLC), but acquired resistance substantially limits its clinical efficacy. Recently, DNA methylation has been identified as an essential contributor to chemoresistance. However, the precise DNA methylation regulatory mechanism of cisplatin resistance remains unclear. Here, we found that nicotinamide nucleotide transhydrogenase (NNT) was silenced by DNA hypermethylation in cisplatin resistance A549 (A549/DDP) cells. Also, the DNA hypermethylation of NNT was positively correlated to poor prognosis in NSCLC patients. Overexpression of NNT in A549/DDP cells could reduce their cisplatin resistance, and also suppressed their tumor malignancy such as cell proliferation and clone formation. However, NNT enhanced sensitivity of A549/DDP cells to cisplatin had little to do with its function in mediating NADPH and ROS level, but was mainly because NNT could inhibit protective autophagy in A549/DDP cells. Further investigation revealed that NNT could decrease NAD+ level, thereby inactivate SIRT1 and block the autophagy pathway, while re-activation of SIRT1 through NAD+ precursor supplementation could antagonize this effect. In addition, targeted demethylation of NNT CpG island via CRISPR/dCas9-Tet1 system significantly reduced its DNA methylation level and inhibited the autophagy and cisplatin resistance in A549/DDP cells. Thus, our study found a novel chemoresistance target gene NNT, which played important roles in cisplatin resistance of lung cancer cells. Our findings also suggested that CRISPR-based DNA methylation editing of NNT could be a potential therapeutics method in cisplatin resistance of lung cancer.

Functional effects of arthroscopic modified Broström procedure on lateral ankle instability: A pilot study.

BACKGROUND: This study aims to assess the mechanical and functional effects of the arthroscopic modified Broström procedure (AMBP) on patients with lateral ankle instability. METHODS: Eight patients with unilateral ankle instability treated with AMBP and eight healthy subjects were recruited. Healthy subjects, preoperative and one-year postoperative patients were assessed using outcome scales and the Star Excursion Balance Test (SEBT) for dynamic postural control. One-dimensional statistical parametric mapping was performed to compare ankle angle and muscle activation curve during stair descent. RESULTS: The patients with lateral ankle instability showed good clinical outcomes and increased posterior lateral reach during the SEBT after the AMBP (p = 0.046). The medial gastrocnemius activation after initial contact was reduced (p = 0.049), and the peroneal longus activation after initial contact was promoted (p = 0.014). CONCLUSION: The AMBP has functional effects of promoting dynamic postural control and peroneal longus activation within one year of follow-up, which can benefit patients with functional ankle instability. However, the medial gastrocnemius activation was unexpectedly reduced post operation.

Assessing the neurotoxicity of airborne nano-scale particulate matter in human iPSC-derived neurons using a transcriptomics benchmark dose model.

Airborne nano-scale particulate matter (nPM) exposure is a risk factor for neurological diseases. However, to date, there has been no comprehensive evaluation of ambient nPM's neurotoxicity. We examined the toxic effects of nPM on human neurons derived from induced pluripotent stem cells (iPSCs) at doses ranging from 0 to 200 µg/mL, and employed whole-genome RNA-sequencing in different dose groups to gain further insight into the neurotoxicity of ambient nPM. Our findings showed that nPM was absorbed by neurons, and induced a variety of toxic effects. The apical benchmark dose lower confidence bound (aBMDL) values of each effect endpoint were ranked as follows, in ascending order: mitochondrial membrane potential, neurite length, early apoptosis, cell viability. BMD analysis based on transcriptomic data revealed that the point of departure (PoD) of the 20 pathways with the lowest p-values (0.75 µg/mL), the top 20 upstream regulators (0.79 µg/mL) and the neurological diseases (0.77 µg/mL) could be appropriate for nPM neurotoxicity evaluation. The transcriptomic PoDs (tPoDs) were similar to apical PoDs (aPoDs) since their absolute fold differences were within 10-fold. Further analysis of the transcriptomic data revealed that nPM exposure could disturb the pathways related to ferroptosis, neurotransmitters, xenobiotic metabolism, etc., which might be critical in regulating nPM neurotoxicity. We also found that low-dose nPM induced cytokine signaling pathways, while high doses of nPM activated cell-cycle regulation and DNA repair pathways. Our results indicate that BMD modeling based on transcriptomic data could be useful in illustrating the neurotoxic mechanism, and also could be a promising method for evaluating the potential health risks of nPM.

Surgical management of concurrent lateral ankle instability and osteochondral lesions of the talus increases dynamic sagittal ankle range of motion.

PURPOSE: A biomechanical study, in which imaging modalities are used to strictly include patients with concurrent lateral ankle instability (LAI) and osteochondral lesions of the talus (OLT), is needed to demonstrate the static and dynamic ankle range of motion (ROM) restriction in these patients, and determine whether ankle ROM restriction can be corrected postoperatively. METHODS: Eight patients with concurrent LAI and OLT treated with the arthroscopic modified Broström procedure and microfracture were recruited from June 2019 to January 2020. Patients were assessed using outcome scales, static ankle ROM, and a stair descent gait analysis for dynamic ankle ROM, a day prior to surgery and one year postoperatively. Eight healthy subjects were assessed using the same modalities upon recruitment. Operative outcomes and variables during stair descent were documented and compared among the preoperative, postoperative, and healthy groups. A curve analysis, one-dimensional statistical parametric mapping, was performed to compare the dynamic ankle kinematics and muscle activation curves over the entire normalised time series. RESULTS: The functional outcomes of patients with concurrent LAI and OLT were significantly worse than those of healthy subjects preoperatively, but were partially improved postoperatively. Patients had decreased static and dynamic ROM preoperatively, and static ROM did not significantly increase postoperatively (preoperative, 39.6 ± 11.3; postoperative, 44.9 ± 7.1; healthy, 52.0 ± 4.6; p = 0.021). Patients showed increased dynamic ankle flexion ROM (preoperative, 41.2 ± 11.6; postoperative, 53.6 ± 9.0; healthy, 53.9 ± 3.4; p = 0.012) postoperatively, as well as increased peroneus longus activation (preoperative, 35.8 ± 12.0; postoperative, 55.4 ± 25.1; healthy, 71.9 ± 13.4; p = 0.002) and muscle co-contraction of the tibialis anterior and peroneus longus (preoperative, 69.4 ± 23.4; postoperative, 88.4 ± 9.3; healthy, 66.2 ± 18.1; p = 0.045). CONCLUSIONS: Patients with concurrent LAI and OLT had decreased static and dynamic sagittal ankle ROM and altered neuromuscular activation patterns. The arthroscopic modified Broström procedure and microfracture did not significantly increase the static sagittal ankle ROM. However, the dynamic sagittal ankle ROM, peroneus longus activation and muscle co-contraction of the tibialis anterior and peroneus longus increased postoperatively. LEVEL OF EVIDENCE: IV.

Whether the newly modified rhizotomy protocol is applicable to guide single-level approach SDR to treat spastic quadriplegia and diplegia in pediatric patients with cerebral palsy?

PURPOSE: Our aim was to test whether the newly modified rhizotomy protocol which could be effectively used to guide single-level approach selective dorsal rhizotomy (SL-SDR) to treat spastic hemiplegic cases by mainly releasing those spastic muscles (target muscles) marked pre-operatively in their lower limbs was still applicable in spastic quadriplegic or diplegic cerebral palsy (CP) cases in pediatric population. METHODS: In the current study, we retrospectively conducted a cohort review of cases younger than 14 years of age diagnosed with spastic quadriplegic or diplegic CP who undergone our modified protocol-guided SL-SDR in the Department of Neurosurgery, Children's Hospital of Shanghai since July 2016 to November 2017 with at least 12 months post-op intensive rehabilitation program (pre-op GMFCS level-based). Clinical data including demographics, intra-operative EMG responses interpretation, and relevant assessment of included cases were taken from the database. Inclusion and exclusion criteria were set for the selection of patients in the current study. Muscle tone (modified Ashworth scale) and strength of those spastic muscles (muscle strength grading scale), range of motion (ROM) of those joints involved, the level of Gross Motor Function Classification System (GMFCS), and Gross Motor Function Measure 66 items (GMFM-66) score of those cases were our focus. RESULTS: A total of 86 eligible cases were included in our study (62 boys). Among these patients, 61.6% were quadriplegic. Pre-operatively, almost 2/3 of our cases were with GMFCS levels II and III. Mean age at the time of surgery in these cases was 6.2 (3.5-12) years. Pre-op assessment marked 582 target muscles in these patients. Numbers of nerve rootlets tested during SDR procedure were between 52 and 84 across our cases, with a mean of 66.5 ± 6.7/case. Among those tested (5721 in 86 cases), 47.9% (2740) were identified as lower limb-related sensory rootlets. Our protocol successfully differentiated sensory rootlets which were considered to be associated with spasticity of target muscles across all our 86 cases (ranged from 3 to 21). Based on our protocol, 871 dorsal nerve rootlets were sectioned 50%, and 78 were cut 75%. Muscle tone of those target muscles reduced significantly right after SL-SDR procedure (3 weeks post- vs. pre-op, 1.7 ± 0.5 vs. 2.6 ± 0.7). After an intensive rehabilitation program for 19.9 ± 6.0 months, muscle tone continued to decrease to 1.4 ± 0.5. With the reduction of muscle tone, strength of those target muscles in our cases improved dramatically with statistical significance achieved (3.9 ± 1.0 at the time of last follow-up vs. 3.3 ± 0.8 pre-op), and as well as ROM. Increase in GMFCS level and GMFM-66 score was observed at the time of last follow-up with a mean of 0.4 ± 0.6 and 6.1 ± 3.2, respectively, when compared with that at pre-op. In 81 cases with their pre-op GMFCS levels II to V, 27 (33.3%) presented improvement with regard to GMFCS level upgrade, among which 4 (4.9%) even upgraded over 2 levels. Better results with regard to upgrading in level of GMFCS were observed in cases with pre-op levels II and III when compared with those with levels IV and V (24/57 vs. 3/24). Upgrading percentage in cases younger than 6 years at surgery was significantly greater than in those older (23/56 vs. 4/25). Cases with their pre-op GMFM-66 score ≥ 50 had greater score increase of GMFM-66 when compared with those less (7.1 ± 3.4 vs. 5.1 ± 2.8). In the meanwhile, better score improvement was revealed in cases when SDR performed at younger age (6.9 ± 3.3 in case ≤ 6 years vs. 4.7 ± 2.7 in case > 6 years). No permanent surgery-related complications were recorded in the current study. CONCLUSION: SL-SDR when guided by our newly modified rhizotomy protocol was still feasible to treat pediatric CP cases with spastic quadriplegia and diplegia. Cases in this condition could benefit from such a procedure when followed by our intensive rehabilitation program with regard to their motor function.

Can Repeated Ponseti Management for Relapsed Clubfeet Produce the Outcome Comparable With the Case Without Relapse? A Clinical Study in Term of Gait Analysis.

BACKGROUND: The prevention and treatment of relapsed clubfoot remained challenging tasks. There were controversies as to treatment options and management, such as complete subtalar release, application of an Ilizarov external frame, or repeated Ponseti method; and different options were available in different treatment centers. This study was designed to evaluate the clinical outcome of relapsed clubfeet treated by repeated Ponseti method in comparison with the cases without relapse in term of gait analysis and to clarify the clinical efficacy of repeated Ponseti method in treating the relapsed clubfeet. METHODS: Thirty-seven patients (53 feet) were retrospectively identified from our database according to the inclusion and exclusion criteria. Among the 37 patients, 17 cases (25 relapsed clubfeet) were assigned to group I, whereas 20 cases (28 clubfeet without relapse) were assigned to group II. Clinical examination, gait analysis, and kinematic gait deviation criteria from Texas Scottish Rite Hospital for Children were used for evaluation. RESULTS: There was statistically significant difference in the parameters of foot length, stride length, and single limb support time (%gait cycle) between the 2 groups (P<0.05). No statistically significant difference was found in the kinematic parameters of total hip, knee, and ankle excursion, peak knee and ankle flexion and extension, and internal foot progression (P>0.05). There was no statistically significant difference in peak hip, knee, and ankle flexion moment, peak knee valgus moment, and peak ankle power (P>0.05). No statistically significant difference was found in equinus and calcaneus gait, increased ankle dorsiflexion, foot drop, and internal foot progression angle (P>0.05). CONCLUSIONS: Repeated Ponseti method for relapsed clubfeet can yield good or excellent clinical results. We recommend repeated Ponseti method as the treatment choice for relapsed clubfeet in the early stage. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Feasibility and effectiveness of a newly modified protocol-guided selective dorsal rhizotomy via single-level approach to treat spastic hemiplegia in pediatric cases with cerebral palsy.

PURPOSE: It still remains challenging to treat CP cases with spastic hemiplegia using SDR via a single-level approach when guided by the traditional EMG response grading system. Our aim was to assess the feasibility and effectiveness of a newly modified protocol-guided single-level laminectomy SDR to treat such pediatric patients. METHODS: A retrospective cohort review was conducted in the CP cases with spastic hemiplegia undergone our newly modified protocol-guided single-level approach SDR since May 2016 to October 2017, and followed by intensive rehabilitation program for at least 12 months in both Shanghai Children's Hospital and Shanghai Rehabilitation and Vocational Training Center for the Disabled. Inclusion and exclusion criteria were set for the selection of patients in the current study. Our study focused on the setup, EMG recording interpretation, and outcome measures for this newly modified rhizotomy scheme. RESULTS: Eleven cases were included in the current study. Based on our new rhizotomy protocol, a total of 34 rootlets over our 11 cases were cut (2 in 4, 3 in 4, 4 in 1, and 5 rootlets in 2 cases, respectively). After SDR and the following rehabilitation program at a mean duration of 19 months, muscle tone of those "target muscles" in affected lower extremities which identified during pre-op assessment decreased by a mean of 1.4 degrees (Modified Ashworth Scale) in our cases. Strength of those target muscles and ROM of joints involved in their lower limbs were reported to have improved significantly as well. All cases showed major progress with regard to their motor function. A mean of about 10-point increase of GMFM-66 score was reported, and five of six cases who were with GMFCS level II preoperatively improved their GMFCS level at the last assessment. Kinematics of joints of hip, knee, and ankle on the affected side in our cases demonstrated a major correction, along with improvement of their foot pressure patterns to the ground during their gait cycles. Surgery-related complications, such as cerebral-spinal fluid leak/infection, long-term hypoesthesia, or urinary/bowel incontinence were not recorded in the current study. CONCLUSION: Single-level SDR when guided by our simplified rhizotomy protocol is feasible and effective to treat pediatric CP cases with spastic hemiplegia.

Kinematic analysis in post-stroke patients with moderate to severe upper limb paresis and non-disabled controls.

BACKGROUND: Kinematic analysis has been recommended to quantify the upper limb motor function after stroke. However, previous studies have rarely reported the kinematic data of the post-stroke patients with moderate to severe upper limb paresis due to the poor accomplishment of the complex tasks. METHODS: 27 post-stroke individuals and 20 non-disabled people participated in the study. The trunk and upper limb movements during the Hand-to-mouth task were captured by the motion capture system and upper extremity kinematic analysis software automatically. The subgroup analysis within stroke group were conducted layering by the Fugl-Meyer Assessment for Upper Extremity scores (severe: 16-31; moderate: 32-50). FINDINGS: The paretic upper limbs in the stroke group tended to use more trunk and shoulder compensatory strategies to offset the impact of spasticity and weakness compared with non-disabled controls. The less-affected limbs in the stroke group also showed abnormal kinematic data. There were significant differences between the kinematic metrics of severe and moderate subgroups. INTERPRETATION: The Hand-to-mouth task is a good and feasible option for kinematic analysis of these patients. It is essential to layer the severity of the paresis and put more emphasis on trunk movements in the future kinematic studies.

Histone H3K36me3 mediates the genomic instability of Benzo[a]pyrene in human bronchial epithelial cells.

Histone modifications maintain genomic stability and orchestrate gene expression at the chromatin level. Benzo [a]pyrene (BaP) is the ubiquitous carcinogen widely spread in the environment, but the role and regulatory mechanism of histone modification in its toxic effects remain largely undefined. In this study, we found a dose-dependent reduction of histone H3 methylations at lysine4, lysine9, lysine27, lysine36 in HBE cells treated with BaP. We observed that inhibiting H3K27 and H3K36 methylation impaired cell proliferation, whereas the loss of H3K4, H3K9, H3K27, and H3K36 methylation led to increased genomic instability and delayed DNA repair. H3K36 mutation at both H3.1 and H3.3 exhibited the most significant impacts. In addition, we found that the expression of SET domain containing 2 (SETD2), the unique methyltransferase catalyzed H3K36me3, was downregulated by BaP dose-dependently in vitro and in vivo. Knockdown of SETD2 aggravated DNA damage of BaP exposure, which was consistent with the effects of H3K36 mutation. With the aid of chromatin immunoprecipitation (ChIP) -seq and RNA-seq, we found that H3K36me3 was responsible for transcriptional regulation of genes involved in pathways related to cell survival, lung cancer, metabolism and inflammation. The enhanced enrichment of H3K36me3 in genes (CYP1A1, ALDH1A3, ACOXL, WNT5A, WNT7A, RUNX2, IL1R2) was positively correlated with their expression levels, while the reduction of H3K36me3 distribution in genes (PPARGC1A, PDE4D, GAS1, RNF19A, KSR1) were in accordance with the downregulation of gene expression. Taken together, our findings emphasize the critical roles and mechanisms of histone lysine methylation in mediating cellular homeostasis during BaP exposure.

[Features of different contemporary acupuncture and moxibustion schools in the treatment of post-stroke spastic paralysis].

Acupuncture and moxibustion has certain advantages in the treatment of post-stroke spastic paralysis，but the treatment methods and diagnosis and treatment ideas are complicated. This paper sortes out the representative contemporary acupuncture and moxibustion schools in the treatment of post-stroke spastic paralysis, analyzes their academic origins，summarizes and compares the theory，acupoint selection and technique characteristics of different schools in the diagnosis and treatment of this disease，so as to provide some references for guiding optimal treatment schemes selection in clinic.

The transcription activity of OTX2 on p16 expression is significantly blocked by methylation of CpG shore in non-promoter of lung cancer cell lines.

Background: The aberrant expression of the classical tumor suppressor gene p16 is a frequent event in lung cancer mainly due to the hypermethylation of its 5'-cytosine-phosphate-guanine-3' island (Cgi). However, whether methylation happens in other regions and how p16 expression and function are affected are largely unknown. Methods: Clustered Regularly Interspaced Short Palindromic Repeats/dCas9 (CRISPR/dCas9) technology was used for methylation editing at specific site of p16. The effects of methylation editing were detected by 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium, inner salt (MTS), transwell migration and wound healing tests. Chromatin immnoprecipitation-quantitative polymerase chain reaction (CHIP-qPCR) was performed to explore the impact of Cgi shore methylation on the binding abilities of transcription factors (TFs) including YY1, SP1, ZNF148 and OTX2 to p16 gene. A rescue experiment was performed to verify the regulatory effect of OTX2 on p16. The negative relationship between p16 expression and the methylation level of Cgi shore in non-promoter region was further verified with datasets from The Cancer Genome Atlas (TCGA) program and lung adenocarcinoma (LUAD) patients' samples. Results: The suppressive effect of p16 Cgi shore methylation on its expression was demonstrated in both HEK293 and A549 cells using CRISPR/dCas9-mediated specific site methylation editing. Methylation of the Cgi shore in the p16 non-promoter region significantly decreased its expression and promoted cell growth and migration. The ability of OTX2 bound to p16 was significantly reduced by 19.35% after methylation modification. Over-expression of OTX2 in A549 cells partly reversed the inhibitory effect of methylation on p16 expression by 19.04%. The verification results with TCGA and LUAD patients' samples supported that the p16 Cgi shore is a key methylation regulatory region. Conclusions: Our findings suggested that methylation of the Cgi shore in the p16 non-promoter region can hamper the transcriptional activity of OTX2, leading to a reduction in the expression of p16, which might contribute to the development of lung cancer.

[Effects of tuina on the mechanical properties of skeletal muscles of four limbs in patients with chronic fatigue syndrome].

OBJECTIVE: To study the effects of tuina on the mechanical properties of skeletal muscles of four limbs in patients with chronic fatigue syndrome (CFS). METHODS: Thirty CFS patients were recruited as the test group, while another 30 healthy volunteers were recruited as the healthy control group. Patients in the test group received tuina therapy, 30 min each time, once every other day, for totally 10 times. Isokinetic testing technology was used to compare peak torque (PT), total watt (TW), average power (AP), and flexor/extensor (F/E) ratio in the elbow and knee muscles of CFS patients before and after treatment. The Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale was used to evaluate the fatigue degree before and after treatment, and compared with the healthy control group. RESULTS: After treatment the FACIT fatigue scale score decreased significantly in the test group when compared with before treatment (27.5 +/- 9.1 vs 42.5 +/- 11.2), showing statistical difference (P < 0.05). The pre-treatment PT, TW, AP, and F/E ratio in the skeletal muscle were all lower in the test group than in the healthy control group. Compared with before treatment in the test group, patients' elbow 60 degrees/s angular velocity values during exercise extensor PT and TW, knee 60 degrees/s and 180 degrees/s angular velocity values during exercise flexor PT and TW increased significantly; elbow extensor and knee extensor, flexor AP was significantly elevated; knee in 180 degrees/s angular velocity of movement F/E ratio significantly increased, and all the differences were statistically significant (P < 0.05). The improvement of the fatigue degree in CFS patients and elbow in 60 degrees/s angular velocity values under the flexor and extensor TW, and flexor AP value of the degree of improvement were negatively correlated (r = -0.282, -0.482, -0.285, P < 0.05, P < 0.01). Meanwhile, the muscles with the knee in 180 degrees/s angular velocity was negatively correlated with the F/E ratio of the degree of improvement (r = -0. 330, P < 0.05). CONCLUSIONS: CFS patients have lowered mechanical properties of four limbs. Tuina therapy can improve the biomechanical properties of limb skeletal muscle and reduce the overall degree of fatigue in patients. The changes of limb skeletal muscle and mechanical properties can provide objective reference for the clinical diagnosis and assessment of CFS.

Concomitant osteochondral lesions of the talus affect the stair descent biomechanics of patients with chronic ankle instability: A pilot study.

BACKGROUND: Previous studies on the kinematics of patients with chronic ankle instability (CAI) that did not incorporate MRI and arthroscopic assessment could not differentiate between patients with CAI without osteochondral lesion of the talus (OLT) and patients with CAI and OLT and have thus presented contradictory results. RESEARCH QUESTION: This study aimed to investigate the kinematic and electromyographic differences between patients with and without OLT. METHODS: Sixteen subjects with CAI (eight without OLT and eight with OLT confirmed through MRI and arthroscopic assessment) and eight healthy subjects underwent gait analysis in a stair descent setting. The three groups' patient-reported outcomes; ankle joint range of motion in flexion, inversion and rotation; and muscle activation of the peroneus, tibialis anterior, and gastrocnemius during a gait cycle were analyzed and compared. A curve analysis, namely, one-dimensional statistical parametric mapping, was performed to compare the dynamic ankle kinematics and muscle activation curves over the entire normalized time series. RESULTS: The patients with and without OLT had no difference in patient-reported outcomes. The maximal ankle plantarflexion of the patients without OLT and the healthy subjects was significantly larger than that of patients with OLT (p = 0.005). The maximal ankle internal rotation of patients without OLT was significantly larger than that of patients with OLT (p = 0.048). The peroneal activation during 0-6% of the gait cycle of patients with OLT was reduced compared with the healthy subjects. SIGNIFICANCE: Patients with CAI and OLT and patients with CAI without OLT have no difference in patient-reported outcomes, but patients with OLT can be differentiated using the post-initial-contact peroneal activation deficit and the restriction of ankle plantarflexion and internal rotation during stair descent. These variables can be utilized to monitor the function of patients with CAI and their possibility of developing OLT.

Improvement of the gait pattern after selective dorsal rhizotomy derives from changes of kinematic parameters in the sagittal plane.

Objective: Selective dorsal rhizotomy (SDR) can decrease spasticity in children suffering from spastic cerebral palsy (SCP) and thus improve their moving ability when supplemented with the post-operational rehabilitation program. In this case, the study aims to investigate the gait changes in children with mild SCP after SDR in short-term follow-up. Methods: The information of ambulatory SCP cases who underwent SDR in our center was retrospectively reviewed, and comparisons of changes in spasticity, motor function and data of gait analysis before and after SDR were analyzed. Results: In total, 32 cases were included in this study, with a mean age of 5.9 ± 2.1 years old. Noticeable decrease was found in the median value of the pre-operational MAS score after SDR at last follow-up in both sides of adductors, gastrocnemius, soleus, and left hamstrings. The Gross Motor Function Measure-66 score increased from 70.6 ± 9.2 to 73.4 ± 8.2, and the gait deviation index increased after SDR compared with the pre-operational data (right side: 65.8 ± 8.8 vs. 60.1 ± 10.7; left side: 63.5 ± 10.1 vs. 57.0 ± 9.9). Noticeable changes were found that the maximum angle of affected ankles in the sagittal plane (the dorsal-flexion angle) increased from 2.5° to 8.2°, the angles at initial contact (1% gait cycle) of affected knees in the sagittal plane decreased from 34.0° to 27.8°, and the angles at the end of swing phase (100% gait cycle) of affected knees in the sagittal plane decreased from 35.8° to 28.3°. Conclusion: In short-term follow-up, SDR can lower spasticity in children with SCP. Post-operational gait analysis showed improvements in gross motor function and gait, which derived from the changes in the sagittal plane (ankle and knee). A longer follow-up duration is thus needed to clarify the long-term outcome.

Copper-Catalyzed Selective Oxidative Cross-Coupling of Tryptophols and Tryptamines To Access Heterocyclic 3a,3a'-Bisindolines.

The first example of cyclization cross-coupling of tryptophols and tryptamines has been realized by copper catalysis with air or oxone as the terminal oxidant, resulting in the direct construction of a new class of heterocyclic 3a,3a'-bisindolines in moderate to good yields with high chemoselectivities. A series of mechanistic control experiments were also conducted, indicating that the copper catalyst selectively coordinates with the nitrogen moiety of the tryptamine to initiate the oxidation, and a nucleophilic-alkylation process is proposed for the carbon-carbon bond-forming in the reaction. The novel synthetic strategies and molecular skeletons outlined in this work provide new ideas and concepts for the design of other useful reaction and potential drugs.

Determination of tipping point in course of PM2.5 organic extracts-induced malignant transformation by dynamic network biomarkers.

The dynamic network biomarkers (DNBs) are designed to identify the tipping point and specific molecules in initiation of PM2.5-induced lung cancers. To discover early-warning signals, we analyzed time-series gene expression datasets over a course of PM2.5 organic extraction-induced human bronchial epithelial (HBE) cell transformation (0th~16th week). A composition index of DNB (CIDNB) was calculated to determine correlations and fluctuations in molecule clusters at each timepoint. We identified a group of genes with the highest CIDNB at the 10th week, implicating a tipping point and corresponding DNBs. Functional experiments revealed that manipulating respective DNB genes at the tipping point led to remarkable changes in malignant phenotypes, including four promoters (GAB2, NCF1, MMP25, LAPTM5) and three suppressors (BATF2, DOK3, DAP3). Notably, co-altered expression of seven core DNB genes resulted in an enhanced activity of malignant transformation compared to effects of single-gene manipulation. Perturbation of pathways (EMT, HMGB1, STAT3, NF-κB, PTEN) appeared in HBE cells at the tipping point. The core DNB genes were involved in regulating lung cancer cell growth and associated with poor survival, indicating their synergistic effects in initiation and development of lung cancers. These findings provided novel insights into the mechanism of dynamic networks attributable to PM2.5-induced cell transformation.

[A study of median frequencies of skeletal muscle undergoing Tuina intervention in patients with chronic fatigue syndrome].

OBJECTIVE: To study the changes in median frequency (MF) from a surface electromyogram of skeletal muscles and functional assessment of chronic illness therapy (FACIT) figure scale scores for patients with chronic fatigue syndrome (CFS) before and after Tuina treatment. METHODS: A controlled clinical trial was adopted. Thirty-two patients suffering from CFS were enrolled according to the inclusion criteria from outpatient department of Shanghai Yueyang Hospital of Integrated Chinese and Western Medicine in China; thirty normal people whose gender, age, height and body mass were concordant with the CFS patients were selected as the normal group. Surface electromyography was used to detect the median frequency (MF) of biceps, quadriceps, and waist and back muscle before and after a 20-day course of treatment. CFS patients also were asked to fill out the figure scale of FACIT to evaluate the degree of fatigue. RESULTS: There was no significant difference in surface electromyography MF of myoelectric signal of biceps and quadriceps between CFS and normal person; however, the waist and back muscle MF of the normal person was significantly lower than that of the CFS patients. Before and after treatment, there were no obvious changes in the MF of myoelectric signals of all muscles. Tuina significantly decreased the scale score of FACIT. CONCLUSION: Tuina can improve the symptom of patients with CFS.