Anti-osteoporotic effects of Yi Mai Jian on bone metabolism of ovariectomized rats.

Yi Mai Jian herbal formula (YMJ) is formulated with Eucommiae Folium, Astragali Radix, Ligustri Lucidi Fructus, and Elaeagnus Fructus to improve bone function in traditional Chinese medicine. The anti-osteoporotic effects of YMJ in bone metabolism were evaluated in ovariectomized (OVX) rats. The skeletal structure of the femur and vertebrae was analyzed after treating OVX rats with YMJ for 114 days. The results showed that YMJ significantly increased the bone mineral density (BMD) and trabecular number (Tb. N) of the femur and 5th lumbar vertebrae and reduced trabecular separation (Tb. Sp). Moreover, trabecular bone volume/total tissue volume (BV/TV), bone stiffness, and maximum femur load were significantly increased. The serum concentrations of NTX1 and PYD were significantly decreased. According to these results, YMJ could ameliorate osteoporosis in ovariectomized rats. Eucommiae Folium and Elaeagnus Fructus inhibited osteoclast differentiation, Ligustri Lucidi Fructus inhibited calcium reabsorption, Astragali Radix stimulated osteoblast proliferation, and Astragali Radix and Eucommiae Folium stimulated mineralization. Therefore, the combination of the four herbs into one formula, YMJ, could alleviate bone remodeling caused by low estrogen levels. We suggest that YMJ could be a healthy food candidate for preventing post-menopausal osteoporosis.

Comparative Efficacy of Different Protein Supplements on Muscle Mass, Strength, and Physical Indices of Sarcopenia among Community-Dwelling, Hospitalized or Institutionalized Older Adults Undergoing Resistance Training: A Network Meta-Analysis of Randomized Controlled Trials.

Aging-related sarcopenia exerts harmful impacts on muscle mass, strength, and physical mobility. Protein supplementation has been demonstrated to augment efficacy of resistance training (RT) in elderly. This study compared the relative effects of different protein supplements on muscle mass, strength, and mobility outcomes in middle-aged and older individuals undergoing RT. A comprehensive search of online databases was performed to identify randomized controlled trials (RCTs) examining the efficacy of protein supplement plus RT in untrained community-dwelling adults, hospitalized, or institutionalized residents who suffered acute or chronic health conditions. Network meta-analysis (NMA) was performed using a frequentist method for all analyses. Treatment effects for main outcomes were expressed as standard mean difference (SMD) with 95% confidence interval (CI). We used the surface-under-the cumulative-ranking (SUCRA) scores to rank probabilities of effect estimation among all identified treatments. Meta-regression analyses were performed to identify any relevant moderator of the treatment efficacy and results were expressed as ß with 95% credible interval (CrI). We finally included 78 RCTs (5272 participants) for analyses. Among the six protein sources identified in this NMA, namely whey, milk, casein, meat, soy, and peanut, whey supplement yielded the most effective treatments augmenting efficacy of RT on muscle mass (SMD = 1.29, 95% CI: 0.96, 1.62; SUCRA = 0.86), handgrip strength (SMD = 1.46, 95% CI: 0.92, 2.00; SUCRA = 0.85), and walking speed (SMD = 0.73, 95% CI: 0.39, 1.07; SUCRA = 0.84). Participant's health condition, sex, and supplementation dose were significant factors moderating the treatment efficacy on muscle mass (ß = 0.74; 95% CrI: 0.22, 1.25), handgrip strength (ß = -1.72; 95% CrI: -2.68, -0.77), and leg strength (ß = 0.76; 95% CrI: 0.06, 1.47), respectively. Our findings suggest whey protein yields the optimal supplements to counter sarcopenia in older individuals undergoing RT.

Injectable, Antioxidative, and Tissue-Adhesive Nanocomposite Hydrogel as a Potential Treatment for Inner Retina Injuries.

Reactive oxygen species (ROS) have been recognized as prevalent contributors to the development of inner retinal injuries including optic neuropathies such as glaucoma, non-arteritic anterior ischemic optic neuropathy, traumatic optic neuropathy, and Leber hereditary optic neuropathy, among others. This underscores the pivotal significance of oxidative stress in the damage inflicted upon retinal tissue. To combat ROS-related challenges, this study focuses on creating an injectable and tissue-adhesive hydrogel with tailored antioxidant properties for retinal applications. GelCA, a gelatin-modified hydrogel with photo-crosslinkable and injectable properties, is developed. To enhance its antioxidant capabilities, curcumin-loaded polydopamine nanoparticles (Cur@PDA NPs) are incorporated into the GelCA matrix, resulting in a multifunctional nanocomposite hydrogel referred to as Cur@PDA@GelCA. This hydrogel exhibits excellent biocompatibility in both in vitro and in vivo assessments, along with enhanced tissue adhesion facilitated by NPs in an in vivo model. Importantly, Cur@PDA@GelCA demonstrates the potential to mitigate oxidative stress when administered via intravitreal injection in retinal injury models such as the optic nerve crush model. These findings underscore its promise in advancing retinal tissue engineering and providing an innovative strategy for acute neuroprotection in the context of inner retinal injuries.

Effects of Protein Supplementation Combined with Resistance Exercise Training on Walking Speed Recovery in Older Adults with Knee Osteoarthritis and Sarcopenia.

Knee osteoarthritis (KOA) is closely associated with sarcopenia, sharing the common characteristics of muscle weakness and low physical performance. Resistance exercise training (RET), protein supplementation (PS), and PS+RET have promise as treatments for both sarcopenia and KOA. However, whether PS+RET exerts any effect on time to recovery to normal walking speed (WS) in older adults with sarcopenia and KOA remains unclear. This study investigated the treatment efficiency of PS+RET on WS recovery among individuals with KOA and sarcopenia. A total of 108 older adults aged ≥ 60 years who had a diagnosis of radiographic KOA and sarcopenia were enrolled in this prospective cohort study. Sarcopenia was defined on the basis of the cutoff values of the appendicular skeletal muscle mass index for Asian people and a slow WS less than 1.0 m/s. The patients were equally distributed to three groups: PS+RET, RET alone, and usual care. The weekly assessment was performed during a 12-week intervention and a subsequent 36-week follow-up period. A cutoff of 1.0 m/s was used to identify successful recovery to normal WS. Kaplan-Meier analysis was performed to measure the survival time to normal WS among the study groups. Multivariate Cox proportional-hazards regression (CPHR) models were established to calculate the hazard ratios (HRs) of successful WS recovery and determine its potential moderators. After the 3-month intervention, PS+RET as well as RET obtained greater changes in WS by an adjusted mean difference of 0.18 m/s (p < 0.0001) and 0.08 (p < 0.05) m/s, respectively, compared to usual care. Kaplan-Meier analysis results showed both RET and PS+RET interventions yielded high probabilities of achieving normal WS over the 12-month follow-up period. Multivariate CPHR results revealed that PS+RET (adjusted HR = 5.48; p < 0.001), as well as RET (adjusted HR = 2.21; p < 0.05), independently exerted significant effects on WS recovery. PS+RET may accelerate normal WS recovery by approximately 3 months compared with RET. Sex and initial WS may influence the treatment efficiency. For patients with KOA who suffer sarcopenia, 12-week RET alone exerts significant effects on WS recovery, whereas additional PS further augments the treatment effects of RET by speeding up the recovery time of WS toward a level ≥ 1.0 m/s, which facilitates the patients to diminish the disease severity or even free from sarcopenia.

Comparative Efficacy of Intra-Articular Injection, Physical Therapy, and Combined Treatments on Pain, Function, and Sarcopenia Indices in Knee Osteoarthritis: A Network Meta-Analysis of Randomized Controlled Trials.

Knee osteoarthritis (KOA) is associated with a high risk of sarcopenia. Both intra-articular injections (IAIs) and physical therapy (PT) exert benefits in KOA. This network meta-analysis (NMA) study aimed to identify comparative efficacy among the combined treatments (IAI+PT) in patients with KOA. Seven electronic databases were systematically searched from inception until January 2023 for randomized controlled trials (RCTs) reporting the effects of IAI+PT vs. IAI or PT alone in patients with KOA. All RCTs which had treatment arms of IAI agents (autologous conditioned serum, botulinum neurotoxin type A, corticosteroids, dextrose prolotherapy (DxTP), hyaluronic acid, mesenchymal stem cells (MSC), ozone, platelet-rich plasma, plasma rich in growth factor, and stromal vascular fraction of adipose tissue) in combination with PT (exercise therapy, physical agent modalities (electrotherapy, shockwave therapy, thermal therapy), and physical activity training) were included in this NMA. A control arm receiving placebo IAI or usual care, without any other IAI or PT, was used as the reference group. The selected RCTs were analyzed through a frequentist method of NMA. The main outcomes included pain, global function (GF), and walking capability (WC). Meta-regression analyses were performed to explore potential moderators of the treatment efficacy. We included 80 RCTs (6934 patients) for analyses. Among the ten identified IAI+PT regimens, DxTP plus PT was the most optimal treatment for pain reduction (standard mean difference (SMD) = -2.54) and global function restoration (SMD = 2.28), whereas MSC plus PT was the most effective for enhancing WC recovery (SMD = 2.54). More severe KOA was associated with greater changes in pain (ß = -2.52) and WC (ß = 2.16) scores. Combined IAI+PT treatments afford more benefits than do their corresponding monotherapies in patients with KOA; however, treatment efficacy is moderated by disease severity.

Effects of Self-Administered Acupressure on Fatigue Following Traumatic Brain Injury: A Randomized Controlled Trial.

BACKGROUND: Fatigue is a common symptom after a traumatic brain injury (TBI) and may persist for weeks or years. However, nonpharmacological management strategies for fatigue alleviations are almost nonexistent; thus, effective fatigue management programs are needed urgently. PURPOSES: We aimed to evaluate the effects of self-administered acupressure programs on post-TBI fatigue and heart rate variability and identify the possible correlation between the improvements in fatigue symptoms and the changes in heart rate variability. DESIGN: This randomized controlled trial included 2-point acupressure (TPA; n = 27), 5-point acupressure (FPA; n = 27), and usual care (UC, control; n = 27) groups who underwent several assessments before and after the study intervention. Heart rate variability was evaluated at baseline, weeks 2 and 3, and treatment completion. METHODS: The TPA and FPA groups self-administered acupressure (3 minutes per acupoint; bilateral), thrice daily for 4 weeks, whereas the UC group received routine treatment without acupressure. RESULTS: Both the TPA and FPA groups exhibited substantial improvements in fatigue symptoms compared with the baseline findings in the UC group. In addition, the TPA and FPA groups exhibited increased high-frequency power and mean number of times per hour in which the changes in successive normal sinus intervals (RR) gradually exceeded 50 ms (pNN50). Changes in high-frequency power and pNN50 were correlated with improvements in post-TBI fatigue symptoms. CONCLUSION: Acupressure may alleviate chronic fatigue and enhance parasympathetic activity in TBI survivors. The enhancement of parasympathetic activity may be correlated with improvements in post-TBI fatigue symptoms. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers should incorporate self-administered acupressure into the care plans for TBI survivors to improve their fatigue symptoms.

Comparison of Clinical and Ultrasound Imaging Outcomes Between Corticosteroid and Hypertonic Dextrose Injections for Chronic Supraspinatus Tendinopathy.

Background: Both corticosteroids and hypertonic dextrose injections are commonly used for chronic supraspinatus tendinopathy. Purpose: To compare the supraspinatus echogenicity and clinical effects of echo-guided hypertonic dextrose versus corticosteroid injection for treating chronic supraspinatus tendinopathy. Study Design: Cohort study; Level of evidence, 3. Methods: The authors performed a secondary data analysis of a previous clinical trial including patients who received normal saline versus hypertonic dextrose injection; patients who received corticosteroid injection were recruited between August 2017 and July 2021. Baseline patient data were matched among these 3 groups at a 1:1:1 ratio. At baseline and 2, 6, and 12 weeks after the intervention, the authors compared morphological changes (supraspinatus thickness and echogenicity) and clinical parameters (visual analog scale [VAS] for pain, Shoulder Pain and Disability Index [SPADI], and range of motion [ROM]). Analysis of variance was used to compare mean changes from baseline among the groups. Results: A total of 75 patients (25 in each group) were included. At 2-week follow-up, both the dextrose and the steroid groups exhibited improvement in VAS scores (mean difference [MD] from baseline: -2.0 in dextrose group; -3.3 in steroid group (P < .001)), SPADI scores (MD from baseline: -10.6 in dextrose group; -24.6 in steroid group (P < .001)), and flexion ROM (MD from baseline: 13.6° in dextrose group; 21.1° in steroid group) (P =.001). At 6 weeks after injection, the hypertonic dextrose group exhibited more favorable echogenic improvement in supraspinatus tendon morphology compared with the other 2 groups (P < .001). However, the steroid group showed significantly more improvement in clinical parameters compared with the other 2 groups at both week 6 (MD from baseline: VAS, -3.2; SPADI, -26.6; flexion ROM, 21.5°) and week 12 (MD from baseline: VAS, -2.5; SPADI, -20.4; flexion ROM, 15.2°) (P < .001 for all). Conclusion: Hypertonic dextrose injection improved supraspinatus echogenicity after 6 weeks but provided short-term symptomatic relief in the patients with chronic supraspinatus tendinopathy when compared with corticosteroid or saline injections. Steroid injection exerted a more favorable clinical effect at weeks 6 and 12 but demonstrated a negative effect on the supraspinatus.

Solar-assisted high-efficient cleanup of viscous crude oil spill using an ink-modified plant fiber sponge.

Rapid and efficient clean-up of viscous crude oil spills is still a global challenge due to its high viscous and poor flowability at room temperature. The hydrophobic/oleophilic absorbents with three-dimensional porous structure have been considered as a promising candidate to handle oil spills. However, they still have limited application in recovering the high viscous oil. Inspired by the viscosity of crude oil depended on the temperature, a solar-heated ink modified plant fiber sponge (PFS@GC) is fabricated via a simple and environmentally friendly physical foaming strategy combined with in-situ ink coating treatment. After wrapping by the polydimethylsiloxane (PDMS), the modified PFS@GC (PFS@GC@PDMS) exhibits excellent compressibility, high hydrophobic (141° in water contact angle), solar absorption (> 96.0%), and oil absorptive capacity (12.0-27.8 g/g). Benefiting from the favorable mechanical property and photothermal conversion capacity, PFS@GC@PDMS is demonstrated as a high-performance absorbent for crude oil clean-up and recovery. In addition, PFS@GC@PDMS can also be applied in a continuous absorption system for uninterrupted recovering of oil spills on the water surface. The proposed solar-heated absorbent design provides a new opportunity for exploring biomass in addressing large-scale oil spill disasters.

Effect of Hypertonic Dextrose Injection on Pain and Shoulder Disability in Patients with Chronic Supraspinatus Tendinosis: A Randomized Double-Blind Controlled Study.

OBJECTIVES: To investigate the effect of hypertonic dextrose injection on pain and disability in patients with chronic supraspinatus tendinosis. The secondary aim was to evaluate its effect on the tendon range of motion (ROM) and morphology. DESIGN: Randomized double-blind placebo-controlled trial. SETTING: Outpatient clinic. PARTICIPANTS: Individuals (N=57) with symptomatic chronic supraspinatus tendinosis. INTERVENTIONS: Participants were randomly administered ultrasound-guided injections of 20% hypertonic dextrose (study group, n=29) or 5% normal saline (control group, n=28). MAIN OUTCOME MEASURES: The primary outcome measure was visual analog scale (VAS) scores for pain and Shoulder Pain and Disability Index (SPADI) scores. Secondary outcomes included the ROM and ultrasound examination findings of the supraspinatus tendon at baseline and at 2, 6, and 12 weeks postintervention. RESULTS: The study group exhibited significant improvements in the VAS (mean difference [MD], -2.1; 95% confidence interval [CI], -2.7 to -1.4; P<.001) and SPADI (MD, -11.6; 95% CI, -16.5 to -6.7; P<.001) scores compared with baseline scores at week 2. However, the effect was not sustained to week 6. Flexion ROM increased at weeks 2 (MD, 14.1; 95% CI, 5.7-22.5; P<.001) and 6 (MD, 8.9; 95% CI, 2.4-15.4; P=.003) compared with baseline. The thickness of the supraspinatus tendon improved at weeks 6 (MD, .50; 95% CI, .26-.74; P<.001) and 12 (MD, .61; 95% CI, .37-.84; P<.001) compared with baseline. The ratio of histograms also improved at weeks 6 (MD, .19; 95% CI, .06-.32; P=.002) and 12 (MD, .26; 95% CI, .10-.41; P<.001) compared with baseline. CONCLUSION: Hypertonic dextrose injection could provide short-term pain and disability relief in patients with chronic supraspinatus tendinosis. Ultrasound imaging at week 6 revealed changed tendon morphology.

Epidemiology of pediatric tracheotomy: A population-based study using National Health Insurance Research Database in Taiwan.

OBJECTIVE: Tracheostomy in children is a surgical procedure with considerable morbidity and mortality. However, there is still a lack of population-based survey in pediatric tracheostomy. This study analyses population-based data in pediatric tracheostomy among different ages in Taiwan. METHODS: This study used National Health Insurance Research Database in Taiwan. All children (aged <18 years) who underwent tracheostomy during 1997-2016 were identified. We retrieved data regarding baseline characteristics, perioperative care, and mortality associated with pediatric tracheostomy, and compared differences in variables between different age groups. RESULTS: We observed that 2300 children received tracheostomy (mean age, 8.7 years; 64% boys). Regarding the age group distribution of the patients, 585 (25.4%) were infants (<1 year), 227 (9.9%) were toddlers (1-3 years), 175 (7.6%) were preschool-aged children (3-6 years), 317 (13.8%) were school-aged children (6-12 years), and 996 (43.3%) were adolescents (12-18 years). Surgical indications included pulmonary disorders (64.9%), neurological disorders (38.4%), trauma (32.3%), head injury (25.2%), and congenital anomalies (21.5%). Of these patients, 94.9% required intensive care unit (ICU) care, with the mean length of ICU stay being 63.8 days. The mean length of hospital stay was 74.5 days. The overall mortality at the last follow-up was 43.96% (1011/2300), and the tracheostomy related mortality at the last follow-up was 1.43% (33/2300). Compared with adolescents, infants more commonly underwent tracheostomy in the northern area (66.7% vs 37.2%, P < .001), more commonly received tracheostomy indicated by congenital anomalies (53.7 vs 4.6%, P < .001), had longer ICU stays, had longer hospital stays (100.7 vs 57.5 days, P < .001), and had a higher 5-year mortality rate (42.4 vs 29.6%, P < .001). Multivariable logistic and Cox regression models revealed that young age was associated with an increased risk of prolonged hospital stay and long-term mortality, respectively. CONCLUSIONS: This study elaborates the epidemiology of pediatric tracheostomy in different age groups.

Designing and pilot testing a novel high-definition transcranial burst electrostimulation device for neurorehabilitation.

Objective.Non-invasive brain stimulation has been promoted to facilitate neuromodulation in treating neurological diseases. Recently, high-definition (HD) transcranial electrical stimulation and a novel electrical waveform combining a direct current (DC) and theta burst stimulation (TBS)-like protocol were proposed and demonstrated high potential to enhance neuroplastic effects in a more-efficient manner. In this study, we designed a novel HD transcranial burst electrostimulation device and to preliminarily examined its therapeutic potential in neurorehabilitation.Approach.A prototype of the transcranial burst electrostimulation device was developed, which can flexibly output a waveform that combined a DC and TBS-like protocol and can equally distribute the current into 4 × 1 HD electrical stimulation by automatic impedance adjustments. The safety and accuracy of the device were then validated in a series ofin vitroexperiments. Finally, a pilot clinical trial was conducted to assess its clinical safety and therapeutic potential on upper-extremity rehabilitation in six patients with chronic stroke, where patients received either active or sham HD transcranial burst electrostimulation combined with occupational therapy three times per week for four weeks.Main results.The prototype was tested, and it was found to comply with all safety requirements. The output parameters were accurate and met the clinical study needs. The pilot clinical study demonstrated that the active HD transcranial burst electrostimulation group had greater improvement in voluntary motor function and coordination of the upper extremity than the sham control group. Additionally, no severe adverse events were noted, but slight skin redness under the stimulus electrode immediately after stimulation was seen.Conclusions.The results demonstrated the feasibility of incorporating the HD electrical DC and TBS-like protocol in our device; and the novel neuromodulatory device produced positive neurorehabilitation outcomes in a safe fashion, which could be the basis for the future clinical implementation for treating neurological diseases.Trial registration:ClinicalTrials.gov Identifier: NCT04278105. Registered on 20 February 2020.

Characteristics of Optic Disc and Visual Field Changes in Patients with Thyroid-Associated Orbitopathy and Open-Angle Glaucoma.

This study aimed to characterize the changes in the visual field (VF) patterns and disc morphology of patients with thyroid-associated orbitopathy (TAO) and open-angle glaucoma (OAG). A retrospective review of the medical records at the Tri-Service General Hospital in Taiwan identified 396 eyes of 198 patients with thyroid-associated glaucoma. A final follow-up of VF examination in 140 eyes revealed 114 eyes with VF defects, indicating disease progression. The characteristics of and changes in disc morphology, optical coherence tomography findings, and VF defects were statistically analyzed. The most common VF defects at the initial diagnosis and the end of the follow-up period were inferior partial arcuate (17%) and paracentral (15%) defects, respectively. The most common VF defect in patients with unspecific disc signs was an unspecific scotoma (13%). The most common optic disc feature was disc cupping (51%), followed by parapapillary atrophy (48%). The most frequent location of nerve fiber layer thinning was the inferotemporal region (48%). VF defects showed a significantly more pronounced progression in the non-nerve fiber bundle group than in the nerve fiber bundle group (p < 0.001). This study details the characteristics and progression of disc morphology and VF defects in patients with TAO and OAG.

The risk of fibromyalgia in patients with iron deficiency anemia: a nationwide population-based cohort study.

Since iron is essential for neurotransmitter synthesis, decreased iron stores might lead to reduced production of biogenic amines which phenomenon was shown in Fibromyalgia (FM) patients. The aims are to investigate the association of iron deficiency anemia (IDA) and FM and to find the effects of different interventions. We conducted a study using the Taiwan National Health Insurance Research Database. The IDA cohort consisted of 13,381 patients with newly diagnosed IDA between 2000 and 2008. Each patient with IDA was frequency-matched with one people without IDA, by sex, age and index year. The Cox proportional hazards regression analysis was conducted to estimate the association between IDA and FM risk. The event was the occurrence of FM. The overall incidence density rate of FM in the IDA cohort was higher than in the non-IDA cohort with a multivariable Cox proportional hazards model measured adjusted hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.13-1.25). When using non-IDA group as reference, we compared with different therapies for IDA. The adjusted HRs of FM were 1.38 (95% CI = 1.30-1.47), 1.10 (95% CI = 1.03-1.16), 1.18 (95% CI = 0.98-1.43) and 0.73 (95% CI = 0.58-0.90) for IDA patient without therapy, iron supplement alone, blood transfusion alone and both iron supplement and blood transfusion respectively. Our results suggest IDA is associated with an increased risk of FM. All patients should have iron supplementation both to correct anemia and replenish body stores.

Dysregulated Kras/YY1/ZNF322A/Shh transcriptional axis enhances neo-angiogenesis to promote lung cancer progression.

Angiogenesis enhances cancer metastasis and progression, however, the roles of transcription regulation in angiogenesis are not fully defined. ZNF322A is an oncogenic zinc-finger transcription factor. Here, we demonstrate a new mechanism of Kras mutation-driven ZNF322A transcriptional activation and elucidate the interplay between ZNF322A and its upstream transcriptional regulators and downstream transcriptional targets in promoting neo-angiogenesis. Methods: Luciferase activity, RT-qPCR and ChIP-qPCR assays were used to examine transcription regulation in cell models. In vitro and in vivo angiogenesis assays were conducted. Immunohistochemistry, Kaplan-Meier method and multivariate Cox regression assays were performed to examine the clinical correlation in tumor specimens from lung cancer patients. Results: We validated that Yin Yang 1 (YY1) upregulated ZNF322A expression through targeting its promoter in the context of Kras mutation. Reconstitution experiments by knocking down YY1 under KrasG13V activation decreased KrasG13V-promoted cancer cell migration, proliferation and ZNF322A promoter activity. Knockdown of YY1 or ZNF322A attenuated angiogenesis in vitro and in vivo. Notably, we validated that ZNF322A upregulated the expression of sonic hedgehog (Shh) gene which encodes a secreted factor that activates pro-angiogenic responses in endothelial cells. Clinically, ZNF322A protein expression positively correlated with Shh and CD31, an endothelial cell marker, in 133 lung cancer patient samples determined using immunohistochemistry analysis. Notably, patients with concordantly high expression of ZNF322A, Shh and CD31 correlated with poor prognosis. Conclusions: These findings highlight the mechanism by which dysregulation of Kras/YY1/ZNF322/Shh transcriptional axis enhances neo-angiogenesis and cancer progression in lung cancer. Therapeutic strategies that target Kras/YY1/ZNF322A/Shh signaling axis may provide new insight on targeted therapy for lung cancer patients.

Effects of hypertonic dextrose injection in chronic supraspinatus tendinopathy of the shoulder: a randomized placebo-controlled trial.

BACKGROUND: Rotator cuff lesions are common causes of shoulder pain. Although patients with symptoms caused by chronic rotator cuff tendinopathy can be treated using conservative treatments, some of them may still experience refractory symptoms. Hypertonic dextrose prolotherapy (DPT) may be another treatment choice for these refractory symptoms. AIM: The aim of this study was to evaluate the effects of an ultrasound-guided hypertonic dextrose injection for patients with chronic supraspinatus tendinopathy. DESIGN: Randomized double-blind placebo-controlled trial. SETTING: Academic medical center. POPULATION: Outpatients patients (N.=31) with chronic supraspinatus tendinopathy and shoulder pain for more than six months. METHODS: Study group treated with one dose of an ultrasound-guided hypertonic dextrose (20%) injection at the supraspinatus enthesis site, whereas control patients received one dose of 5% normal saline through the same method. The Visual Analog Scale (VAS), Shoulder Pain And Disability Index (SPADI), shoulder active range of motion (AROM) and ultrasonographic thickness and histogram results of the supraspinatus tendon were evaluated before intervention and at two and six weeks after intervention. The outcome differences between the study and control groups were analyzed by using repeated-measures analysis of variance (ANOVA). RESULTS: In total, 31 patients completed the study. The study group indicated a significant improvement in the VAS (P=0.001), SPADI scores (P=0.017), shoulder AROM of flexion (P=0.039), and abduction (P=0.043) compared with the control group at two weeks after the injection. However, the effect did not sustain until six weeks after the injection. No differences in the histograms and morphological changes (thickness) were noted before and after injection in both groups. CONCLUSIONS: This study revealed that the ultrasound-guided hypertonic dextrose injection relieved pain, disability, and improved shoulder AROM for a short period in patients with chronic supraspinatus tendinopathy. CLINICAL REHABILITATION IMPACT: For patients with chronic shoulder pain and supraspinatus tendinopathy, ultrasound-guided hypertonic dextrose injections can provide relief from pain, disability, and shoulder range of motion for up to two weeks after intervention.

Isolated Soy Protein Supplementation and Exercise Improve Fatigue-Related Biomarker Levels and Bone Strength in Ovariectomized Mice.

Isolated soy protein (ISP) is a well-known supplement and has been reported to improve health, exercise performance, body composition, and energy utilization. ISP exhibits multifunctional bioactivities and also contains branched-chain amino acids (BCAAs), which have been confirmed to positively affect body weight (BW) regulation and muscle protein synthesis. The combined effects of BCAA supplements and exercise in older postmenopausal women with osteoporosis, sarcopenia, and obesity have been inadequately investigated. Therefore, in this study, we evaluated the potential beneficial effects of soy protein supplementation and exercise training on postmenopausal mice. Forty mice (14 weeks old) with ovariectomy-induced osteosarcopenic obesity were divided into five groups (n = 8), namely sham ovariectomy (OVX, control), OVX, OVX with ISP supplementation (OVX+ISP), OVX with exercise training (ET, OVX+ET), and OVX with ISP and ET (OVX+ISP+ET). The mice received a vehicle or soy protein (3.8 g/kg BW) by oral gavage for four weeks, and the exercise performance (forelimb grip strength and exhaustive swimming time) was evaluated. In the biochemical profiles, we evaluated the serum glucose level and tissue damage markers, such as lactate, ammonia, glucose, blood urine nitrogen (BUN), and creatinine phosphate kinase (CPK). The body composition was determined by evaluating bone stiffness and muscle mass. All data were analyzed using one-way repeated measures analysis of variance. The physical performance of the OVX+ISP+ET group did not differ from that of the other groups. The OVX+ISP+ET group exhibited lower levels of serum lactate, ammonia, CPK, and BUN as well as economized glucose metabolism after an acute exercise challenge. The OVX+ISP+ET group also exhibited higher muscle mass and bone strength than the OVX group. Our study demonstrated that a combination of ISP supplementation and exercise reduced fatigue and improved bone function in OVX mice.

The Effects of Thiamine Tetrahydrofurfuryl Disulfide on Physiological Adaption and Exercise Performance Improvement.

Thiamine, named as vitamin B1, is an important cofactor for the critical enzymes regarding to glucose metabolism, like transketolase, pyruvate dehydrogenase, and alpha-ketoglutarate dehydrogenase. The thiamine tetrahydrofurfuryl disulfide (TTFD) is a derivative of thiamine with higher bioavailability and solubility than thiamine and has been widely applied to health maintenance and disease therapy. Higher physical activities are associated with higher thiamine supplements for efficient energy metabolism. Furthermore, the effective dose of TTFD, beneficial to exercise physiological adaption and performance, still be further validated and the safety evaluation were also an important issue to be considered for potential application. ICR (Institute of Cancer Research) strain mice were allocated as 0, 50, 100, and 500 mg/kg dose groups and administrated by oral gavage consecutively for 6 weeks. Physical activities including grip strength and aerobic endurance were measured. Various fatigue-associated biochemical variables such as lactate, glucose, blood urine nitrogen (BUN) or creatine kinase (CK), were also assessed. The levels of liver and muscle glycogen were measured as an indicator of energy storage at the end of the experiment. Toxicity assessments for long-term supplementation were also further evaluated for safety consideration. TTFD supplementation significantly increased the endurance and grip strength and demonstrated beneficial effects on lactate production and clearance rate after an acute exercise challenge. The TTFD supplementation significantly mitigated the BUN and CK indexes after extended exercise and elevated the glycogen content in the liver and muscle tissues. According to body composition, biochemical and histopathological data, daily administration of TTFD for over 6 weeks (subacute toxicity) also demonstrated reasonable safety results for long-term and adequate supplementation. The toxicity of TTFD were also considered as safety for long-term supplementation with indicated doses. Furthermore, the TTDF could be applied to not only the health promotion but also improvement of exercise physiological adaption and the TTFD could be further considered as potential ergogenic aids combined with different nutrient strategy.

Reversible and Precisely Controllable p/n-Type Doping of MoTe2 Transistors through Electrothermal Doping.

Precisely controllable and reversible p/n-type electronic doping of molybdenum ditelluride (MoTe2 ) transistors is achieved by electrothermal doping (E-doping) processes. E-doping includes electrothermal annealing induced by an electric field in a vacuum chamber, which results in electron (n-type) doping and exposure to air, which induces hole (p-type) doping. The doping arises from the interaction between oxygen molecules or water vapor and defects of tellurium at the MoTe2 surface, and allows the accurate manipulation of p/n-type electrical doping of MoTe2 transistors. Because no dopant or special gas is used in the E-doping processes of MoTe2 , E-doping is a simple and efficient method. Moreover, through exact manipulation of p/n-type doping of MoTe2 transistors, quasi-complementary metal oxide semiconductor adaptive logic circuits, such as an inverter, not or gate, and not and gate, are successfully fabricated. The simple method, E-doping, adopted in obtaining p/n-type doping of MoTe2 transistors undoubtedly has provided an approach to create the electronic devices with desired performance.

Prophylactic supplement with melatonin successfully suppresses the pathogenesis of periodontitis through normalizing RANKL/OPG ratio and depressing the TLR4/MyD88 signaling pathway.

Periodontitis (PD) is an inflammatory disease characterized by gingival inflammation and resorption of alveolar bone. Impaired receptor activator of nuclear factor-kappa B ligand/osteoprotegerin (RANKL/OPG) signaling caused by enhanced production of pro-inflammatory cytokines plays an essential role in the pathogenesis of PD. Considering melatonin possesses significant anti-inflammatory property, this study aimed to determine whether prophylactic treatment with melatonin would effectively normalize RANKL/OPG signaling, depress toll-like receptor 4/myeloid differentiation factor 88 (TLR4/MyD88)-mediated pro-inflammatory cytokine activation, and successfully suppress the pathogenesis of PD. PD was induced in adult rats by placing the ligature at molar subgingival regions. Fourteen days before PD induction, 10, 50, or 100 mg/kg of melatonin was intraperitoneally injected for consecutive 28 days. Biochemical and enzyme-linked immunosorbent assay were used to detect TLR4/MyD88 activity, RANKL, OPG, interleukin 1ß, interleukin 6, and tumor necrosis factor-α levels, respectively. The extent of bone loss, bone mineral intensity, and calcium intensity was further evaluated by scanning electron microscopy, micro-computed tomography, and energy-dispersive X-ray spectroscopy. Results indicated that high RANKL/OPG ratio, TLR4/MyD88 activity, and pro-inflammatory cytokine levels were detected following PD. Impaired biochemical findings paralleled well with severe bone loss and reduced calcium intensity. However, in rats pretreated with melatonin, all above parameters were successfully returned to nearly normal levels with maximal change observed in rats receiving 100 mg/kg. As prophylactic treatment with melatonin effectively normalizes RANKL/OPG signaling by depressing TLR4/MyD88-mediated pro-inflammatory cytokine production, dietary supplement with melatonin may serve as an advanced strategy to strengthen oral health to counteract PD-induced destructive damage.

NEUROPROTECTIVE EFFECT OF TERMINALIA CHEBULA EXTRACTS AND ELLAGIC ACID IN PC12 CELLS.

BACKGROUND: Alzheimer's disease (AD) is one of the common neurodegenerative disorders among elderly. The purpose of this study was to determine the neuroprotective effect and mechanisms of action underlying the Terminalia chebula extracts and ellagic acid by using beta-amyloid25-35 (Aß25-35)-induced cell toxicity in an undifferentiated pheochromocytoma (PC12) cell line. MATERIALS AND METHODS: The T. chebula extracts were prepared using the methanol, water, and 95% ethanol. Specifically, the ellagic acid was obtained in our laboratory. Assays including cell toxicity and changes in intracellular reactive oxygen species (ROS) and calcium level were evaluated to examine the neuroprotective effects and mechanisms of the T. chebula extracts and ellagic acid. RESULTS: The methanolic and water extracts of T. chebula and ellagic acid exhibited the strongest neuroprotective activity against Aß25-35-induced PC12 cell damages at 0.5-5.0 µg/ml. The ellagic acid also exhibited partial neuroprotective activity against H2O2-induced PC12 cell damages at 0.5-5.0 µg/ml. The methanolic and water extracts of T. chebula and ellagic acid protected PC12 cells from Aß25-35-mediated cell damages and enhanced cell viability thorough two key mechanisms by: (1) inhibiting ROS production and (2) reducing calcium ion influx. CONCLUSION: The T. chebula represents a promising plant-source as medicine in the application for the treatment of AD. Further investigation focusing on the active component of T. chebula extracts e.g., ellagic acid is crucial to verify the neuroprotective efficacy and mechanisms in vivo.