Network pharmacology analysis and clinical efficacy of the traditional Chinese medicine Bu-Shen-Jian-Pi. Part 3: Alleviation of hypoxia, muscle-wasting, and modulation of redox functions in amyotrophic lateral sclerosis.

OBJECTIVE: The aim of this clinical study is to obtain evidence for the clinical efficacy of Bu-Shen-Jian-Pi formula (BSJP), a traditional Chinese medicine, used for the treatment of amyotrophic lateral sclerosis, a relatively rare, progressive and usually fatal disease possibly associated with alterations in tissue redox status, hypoxia, and muscular injury. BACKGROUND: The active agents in BSJP formula† causing apoptosis, modulation of redox changes, and alterations in the immune status have been studied previously by us using cell cultures. The findings from these investigations have been incorporated into pharmacology databases employed in our analysis of BSJP using network pharmacology analysis/artifical intelligence. This information has been used here in the design of the investigation and to optimize evaluation of the clinical efficacy and usefulness of this herbal medicine, as far as possible using evidence-based medicine criteria. MATERIALS AND METHODS: The design of the study was a randomized multi-center, controlled clinical trial in 127 patients with confirmed diagnoses of amyotrophic lateral sclerosis. Patients and investigator were double-blinded. Clinical efficacy was determined using the Amyotrophic Lateral Sclerosis Symptom Score in Integrative Treatment Scale (ALS-SSIT) and the Amyotrophic Lateral Sclerosis Rating Scale-Revised (ALSFRS-R), together with tests of limb muscle strength using the manual muscle test (MMT), forced vital capacity (FVC), and clinical chemistry laboratory tests over a 20-week observation period. RESULTS: The scores of ALS-SSIT in the BSJP group increased significantly (22%) after treatment. The ALSFRS-R score in the BSJP group decreased significantly after treatment (19%). The rate of decrease in muscle function (MMT score) in most BSJP patients was lower than that in the control group, where the differences in the scores for the trapezius and triceps brachii were statistically significant compared to the control group. The fall in FVC in the BJSP group was significantly slower than in the control group. There were no marked differences observed in the frequency of side effects. Serum vitamin D3 levels in the BSJP group showed greater increases compared to the control group. CONCLUSION: BSJP treatment reduced the rate of progression of amyotrophic lateral sclerosis according to the ALS-SSITS and ALSFRS scores and significantly reduced the rate of deterioration in muscle function in the limbs of amyotrophic lateral sclerosis patients. The modes of action of BSJP in treating amyotrophic lateral sclerosis are probably diverse and multi targeted, some of which may involve regulation of serum vitamin D3 and alleviation of the impairments in liver and kidney function.

Gastrointestinal Talaromyces marneffei infection in a man with AIDS: A case report.

RATIONALE: Reports of intestinal Talaromyces marneffei infection have increased year by year, but those of gastric infection remain rare. Here, we report disseminated talaromycosis with gastric and intestinal ulcers in an AIDS patient who was treated by antifungal agents and a proton pump inhibitor and achieved a satisfactory outcome. PATIENT CONCERNS: A 49-year-old man developed a gastrointestinal illness with main abdominal distension, poor appetite and a positive HIV infection to our AIDS clinical treatment center. DIAGNOSES: Electronic gastrointestinal endoscopy showed that the patient had multiple ulcers in the gastric angle, gastric antrum and large intestine. Gastric Helicobacter pylori infection was ruled out by paraulcerative histopathological analysis and a C14 urea breath test. The diagnosis was confirmed by gastroenteroscopic biopsy and metagenomic next-generation sequencing of gastric ulcer tissue. INTERVENTIONS: Symptomatic and supportive treatments [a proton pump inhibitor and gastrointestinal motility promotion] were initiated. The patient was prescribed sequential antifungal therapy with amphotericin B (0.5 mg/kg·d, 2 weeks) and itraconazole (200 mg, q12h, 10 weeks), and then followed with itraconazole for long-term secondary prevention (200 mg, qd). OUTCOMES: The combined use of antifungal agents and a proton pump inhibitor improved the patient's condition, and he was discharged home 20 days later. He had no gastrointestinal symptom during 1 year of telephone-based follow-up. LESSONS: In endemic areas, clinicians should be alert to the possibility of Talaromyces marneffei infection presenting with gastric ulcers in patients with AIDS, after excluding Helicobacter pylori infection.

Effective Notch-Stress-Based Stress Concentration Factors of the Rib-Deck Weld in Orthotropic Steel Decks Considering the Effect of Asphalt Surfacing.

Effective notch stress (ENS) approaches have many application prospects in fatigue damage assessments; however, an ENS can only be obtained by conducting complex and time-consuming numerical analyses, deterring many engineers from applying such an approach. In terms of the rib-deck weld in orthotropic steel decks (OSDs), predictive formulae for determining the ENS concentration factors (ENS-based SCFs) have been proposed; however, the effect of asphalt surfacing is not involved, which limits their applications in practical engineering. In the present study, refined finite element (FE) models, including asphalt surfacing, were developed to obtain the ENS-based SCFs which could be applied to practical engineering. Parametric analyses were conducted to investigate the effect of the transverse loading position, the combined effect of the transverse loading position and asphalt surfacing, and the effect of the temperature of the asphalt surfacing. The amplification coefficients (kSCF, kSCF1, and kSCF2) were introduced to determine the ENS-based SCFs on the basis of the predictive formulae without considering the effect of asphalt surfacing. Results show that the ENS-based SCFs of the rib-deck weld is considerably affected by the transverse position of wheel loading and the asphalt surfacing. The cubic polynomial function could be employed to fit the numerical results of the ENS-based SCFs and amplification coefficients (kSCF, kSCF1, and kSCF2) with high fitting precision. Predictive formulae for determining the ENS-based SCFs corresponding to arbitrary transverse loading position and temperature of asphalt surfacing are proposed. The validation investigation turns out that the relative error of the proposed formulae is within 10%, indicating the feasibility of using this approach for engineering applications.

Strengthening Cracked Steel Plates with Shape Memory Alloy Patches: Numerical and Experimental Investigations.

To investigate the retarding effect of bonding the shape memory alloy (SMA) patches on crack propagation in steel plates, both numerical and experimental analyses were conducted in the present study. A compact tension (CT) model was developed to clarify the feasibility of bonding the SMA patch to the reinforcement of the mode Ⅰ, mode Ⅱ, and mode Ⅲ cracks. On this basis, parametric analysis was conducted to investigate the strengthening parameters, i.e., the bonding area, the thickness, and the strengthening angle of the SMA patch. Subsequently, fatigue tests on the unreinforced steel plate and cracked steel plate strengthened by the SMA patches were conducted. The monitored stress variation, crack propagation behavior, and fatigue fracture surfaces were analyzed. Findings are meaningful to the application of the SMA reinforcement method in practical engineering.

Mechanical Behavior of Foam-Filled Bamboo Composite Tubes under Axial Compression.

In this paper, a new type of polyurethane foam-filled bamboo composite tube is proposed. Axial compression tests were carried out on unfilled and polyurethane foam-filled bamboo composite tubes. The effects of the foam filler, diameter (50 and 100 mm) and number of winding layers (10, 15 and 20 layers) on the failure mode and energy absorption capacity of the tubes were studied. The test results showed that the failure mode of the unfilled tube was buckling failure, while that of the foam-filled tube was pressure-bearing failure, and the latter was more abrupt. The foam filler enhanced the stability of the wall of the unfilled tube. The interaction between them further increased the bearing capacity of the foam-filled tube and showed a higher platform load at a later stage. In terms of the absorbed energy, specific absorbed energy and average crush load, not all foam-filled tubes were superior to unfilled tubes. However, reducing the height of the bamboo composite tube and increasing the number of winding layers of the bamboo composite tube can effectively increase the positive effect of the foam filler on energy absorption.

Amyotrophic Lateral Sclerosis Symptom Score in Integrative Treatments (ALS-SSIT) for Evaluating Therapeutic Effect of Traditional Chinese Medicine: A Prospective Study.

Objective: To evaluate the reliability, validity, sensitivity, and clinical applicability of a new scale-the amyotrophic lateral sclerosis symptom score in integrative treatments (ALS-SSIT)-for measuring the effect of traditional Chinese medicine (TCM) in patients with amyotrophic lateral sclerosis (ALS). Methods: A total of 160 patients with ALS were enrolled and followed up for 6 months. All patients received TCM. Patients were evaluated at enrollment and at the end of 6 months with a new scale, the ALS-SSIT, developed after extensive consultations with TCM experts with several years of experience in the treatment of ALS. The 36-item Medical Outcomes Study Short Form (SF-36) scale and the amyotrophic lateral sclerosis functional rating scale (ALSFRS) were used as the reference standards. Results: The acceptance rate and completion rate of the ALS-SSIT scale were high, and the content validity was confirmed by experts. Test-retest performed at enrollment and at 6 months showed good reliability of the ALS-SSIT scale (Cronbach α, 0.9172 and 0.9181, respectively). The ALS-SSIT scale score showed significant change at 6 months, indicating the ability to reflect the change in disease severity. Conclusion: The ALS-SSIT appears to be a feasible, reliable, and sensitive tool for the evaluation of the effect of TCM in patients with ALS.

Slower progression of amyotrophic lateral sclerosis with external application of a Chinese herbal plaster-The randomized, placebo-controlled triple-blinded ALS-CHEPLA trial.

Background: Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterized by gradually increasing damage to the upper and lower motor neurons. However, definitive and efficacious treatment for ALS is not available, and oral intake in ALS patients with bulbar involvement is complicated due to swallowing difficulties. Hypothesis/purpose: This study investigated whether the external plaster application of the herbal composition Ji-Wu-Li efficiently slows ALS progression because prior studies obtained promising evidence with oral herbal applications. Study design: The randomized, triple-blinded study compared the efficacy, safety, and tolerability of the application of Ji-Wu-Li plaster (JWLP) with placebo plaster (PLAP). Methods: In total, 120 patients with definite ALS, clinically probable ALS, or clinically probable laboratory-supported ALS were randomized in a 1:1 ratio to receive JWLP or PLAP. Patients were treated and observed for 20 weeks. The primary outcome was the ALSFRS-R score, while the secondary outcomes were the ALS-SSIT score and weight loss. Results: The mean±SD decrease in the ALSFRS-R over 20 weeks differed by 0.84 points in a group comparison (JWLP, -4.44 ± 1.15; PLAP, -5.28 ± 1.98; p = 0.005). The mean increase in the ALS-SSIT over 20 weeks differed by 2.7 points in a group comparison (JWLP, 5.361.15; PLAP, 8.06 ± 1.72; p < 0.001). The mean weight loss over 20 weeks differed by 1.65 kg in a group comparison (JWLP, -3.98 ± 2.61; PLAP, -5.63 ± 3.17; p = 0.002). Local allergic dermatitis suspected as causal to the intervention occurred in 10 of 60 participants in the JWLP group and 9 of 60 participants in the PLAP group. Systemic adverse events were mild, temporary, and considered unrelated to the intervention. Conclusion: The JWLP showed clinical efficacy in the progression of ALS, as measured by the ALSFRS-R, ALS-SSIT, and weight loss in a randomized, placebo-controlled trial. Because skin reactions occurred in both groups, the covering material needs improvement. All of the Ji Wu Li herbal ingredients regulate multiple mechanisms of neurodegeneration in ALS. Hence, JWLP may offer a promising and safe add-on therapy for ALS, particularly in patients with bulbar involvement, but a confirmative long-term multicentre study is required.

Strange attractors and their periodic repetition.

In this paper, we present some important findings regarding a comprehensive characterization of dynamical behavior in the vicinity of two periodically perturbed homoclinic solutions. Using the Duffing system, we illustrate that the overall dynamical behavior of the system, including strange attractors, is organized in the form of an asymptotic invariant pattern as the magnitude of the applied periodic forcing approaches zero. Moreover, this invariant pattern repeats itself with a multiplicative period with respect to the magnitude of the forcing. This multiplicative period is an explicitly known function of the system parameters. The findings from the numerical experiments are shown to be in great agreement with the theoretical expectations.

Use of l-3-n-Butylphthalide within 24 h after intravenous thrombolysis for acute cerebral infarction.

OBJECTIVE: Observe the clinical efficacy of l-3-n-Butylphthalide (NBP) in acute ischemic stroke (AIS) patients within 24 h after intravenous thrombolysis using recombinant tissue plasminogen activator (hereafter termed "IT"). METHODS: One-hundred and seventy-eight patients with AIS were divided randomly into two groups: NBP and control. The former was given a NBP injection within 24 h after IT. After intravenous injection of NBP for 8-10 days, patients switched to soft capsules of NBP before or during meals. NBP treatment was continued for ≥30 days after hospital discharge. In the control group, NBP was not injected within 24 h after IT, and NBP capsules were not given after 8-10 days. Both groups were reviewed for CT or MRI 24 h after IT. The National Institutes of Health Stroke Scale (NIHSS) score was calculated. The number of patients with a modified Rankin scale (mRS) 0-2 before, 24 h, and 90 days after IT was documented. Prevalence of cerebral hemorrhage and reocclusion of blood vessels after IT was calculated. RESULTS: There were no differences in sex, age, blood pressure, blood glucose, or cerebral-infarction types between the two groups before treatment. The NIHSS score 24 h after IT and the percentage of mRS scores 0-2 were not significantly different between the two groups. Compared with the control group, the NIHSS score in the NBP group was significantly improved at 90 days, and the number of patients with a mRS score 0-2 increased significantly. There was no significant difference in hemorrhage prevalence after IT between the two groups. Prevalence of blood-vessel occlusion after IT was significantly lower in the NBP group than that in the control group. CONCLUSION: Use of NBP within 24 h after IT can reduce the prevalence of reocclusion of blood vessels without increasing the risk of cerebral hemorrhage.

Experimental verification of rank 1 chaos in switch-controlled Chua circuit.

In this paper, we provide the first experimental proof for the existence of rank 1 chaos in the switch-controlled Chua circuit by following a step-by-step procedure given by the theory of rank 1 maps. At the center of this procedure is a periodically kicked limit cycle obtained from the unforced system. Then, this limit cycle is subjected to periodic kicks by adding externally controlled switches to the original circuit. Both the smooth nonlinearity and the piecewise linear cases are considered in this experimental investigation. Experimental results are found to be in concordance with the conclusions of the theory.

Magnetically triggered drug release from nanoparticles and its applications in anti-tumor treatment.

The objective of this study was to describe the magnetic nanoparticle-drug conjugates for improved control of drug delivery and drug release. The widely used anticancer agent Doxorubicin (DOX) was successfully conjugated via amine groups to the carboxylic functional groups coating magnetic nanoparticles (fluidMAG-CMX). Following purification of the nanoparticles, the conjugation of DOX on fluidMAG-CMX was confirmed using FTIR spectroscopy and confocal microscopy. The observed drug loading capacity of DOX was 22.3%. Studies of magnetically triggered release were performed under an oscillating magnetic field (OMF). DOX exhibited a significant release percentage of 70% under an OMF, as compared with the release in enzyme. A magnetic field turn-on and turn-off experiment was also conducted to confirm the control of drug release using this triggered system. In vivo experiments indicated that the tumor-inhibitory rate of CMX-DOX NPs under a magnetic field was higher than the other control groups. According to the toxicity assessments, CMX-DOX NPs were not noticeably toxic to mice at our tested dose.

Actigraph evaluation of acupuncture for treating restless legs syndrome.

We evaluated the effects of acupuncture in patients with restless legs syndrome (RLS) by actigraph recordings. Among the 38 patients with RLS enrolled, 31 (M = 12, F = 19; mean age, 47.2 ± 9.7 years old) completed the study. Patients were treated with either standard acupuncture (n = 15) or randomized acupuncture (n = 16) in a single-blind manner for 6 weeks. Changes in nocturnal activity (NA) and early sleep activity (ESA) between week 0 (baseline), week 2, week 4, and week 6 were assessed using leg actigraph recordings, the International Restless Legs Syndrome Rating Scale (IRLSRS), and Epworth Sleepiness Scale (ESS). Standard but not randomized acupuncture reduced the abnormal leg activity of NA and ESA significantly in week 2, week 4, and week 6 based on the changes in the clinical scores for IRLSRS and ESS in week 4 and week 6 compared with the baseline. No side effects were observed. The results indicate that standard acupuncture might improve the abnormal leg activity in RLS patients and thus is a potentially suitable integrative treatment for long-term use.

Shen-zhi-ling oral liquid improves behavioral and psychological symptoms of dementia in Alzheimer's disease.

We evaluated the effects of the traditional Chinese medicine (TCM) Shen-Zhi-Ling oral liquid (SZL) on the behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer's disease (AD). Among 98 patients with AD and BPSD enrolled (mean age, 57.2 ± 8.9 years old), 91 (M = 55, F = 36; mean age, 57.2 ± 9.7 years old) completed the study. Patients took either SZL (n = 45) or placebo granules (n = 46) in a double-blind manner for 20 weeks while maintaining other anticognitive medications unchanged. Changes in BPSD between week 0, week 10, week 20, and week 25 were assessed using the behavioral pathology in Alzheimer's disease (BEHAVE-AD) rating scale and the neuropsychiatric inventory (NPI), detrended fluctuation analysis (DFA) represented by diurnal activity (DA), evening activity (EA), and nocturnal activity (NA) according to actigraphic recordings. SZL but not placebo oral liquid delayed the development of BPSD significantly according to the changes in some of the clinical scores and the EA and NA parameters of DFA at week 20 compared with week 0. No side effects were observed in laboratory tests. The results indicate that SZL might delay the development of BPSD in AD patients and thus is a potentially suitable drug for long-term use.

The use of integrative therapies in patients with amyotrophic lateral sclerosis in shanghai, china.

Objective. To investigate the current use of integrative therapies (IT) in the treatment of patients with amyotrophic lateral sclerosis (ALS). Methods. A cross-sectional, multicenter clinical epidemiological survey was conducted in 12 hospitals in Shanghai. We investigated the type and frequency of IT use and determined whether the use of IT correlated with demographic, social, or disease-specific characteristics in our patient population. Results. A total of 231 (89.5%) of 258 patients with ALS were eligible for the study and 229 (99% of all) of 231 reported the use of at least one IT for the treatment of ALS. Vitamins and Chinese herb decoctions, Chinese herb compounds, massage therapy, and acupuncture were the 5 most commonly used therapies. There was a strong association between education level, income, and use of IT. A household income of more than 75,000 RMB ($49,995) correlated with multiple IT use, and married patients used IT more often than single individuals. The main reasons for using IT were to treat weakness and fatigue, muscle atrophy, the development of ALS, depression, insomnia, limb pain or numbness, and side effects associated with Riluzole. Conclusion. The use of IT is common in patients with ALS in Shanghai. Vitamins and TCM are the most used additional therapies and the widespread and largely unexamined use of IT for ALS requires more attention.