Effects of Different Running Intensity on Serum Levels of IL-6 and TNF-α in Patients with Early Knee Osteoarthritis.

OBJECTIVE: To investigate the effects of different running intensities on interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in patients with early knee osteoarthritis (KOA). STUDY DESIGN: Clinical comparative study. PLACE AND DURATION OF STUDY: Department of Orthopedics, Longyan First Affiliated Hospital of Fujian Medical University, Fujian, China, from January 2019 to January 2021. METHODOLOGY: A total of 131 patients with early KOA admitted to Longyan First Hospital Affiliated to Fujian Medical University from January 2019 to January 2021 were selected and randomly divided into four groups using the random number table method: Group A (static control group, 34 cases), Group B (walking group, 32 cases), Group C (brisk walking group, 32 cases), and Group D (jogging group, 33 cases), and the training duration of the four groups was 6 months. Moreover, the levels of IL-6 and TNF-α, the activity of daily living (ADL), Fugl-Meyer assessment scale (FMA) scores, and adverse events before and after training were compared between the four groups. RESULTS: No statistical significance was observed in the differences of TNF-α, IL-6, ADL-advanced ability, ADL-basic ability, FMA-upper limb, and FMA-lower limb among the four groups before training (p>0.05). After training, the levels of TNF-α and IL-6 of the four groups were decreased, while the scores of FMA and ADL were increased. Group C had the highest FMA-upper limb and FMA-lower limb scores, ADL- advanced ability and ADL-basic ability after training, which were higher than those in groups A, B, and D (p<0.05). No statistical significance could be observed in the difference in the adverse event rate among the four groups during training (X2=3.339, p>0.05). CONCLUSION: Exercise training of different intensities, such as slow walking, brisk walking, and jogging, is touted to enhance the overall recovery of patients with early KOA. The exercise intensity of brisk walking training is moderate, and the activity of daily living and exercise ability of patients are significantly improved after training, while the levels of TNF-α and IL-6 are obviously decreased. KEY WORDS: Knee osteoarthritis, Interleukin-6, Exercise training, Exercise intensity, Tumor necrosis factor α.

Neoadjuvant Chemotherapy-Guided Bladder-Sparing Treatment for Muscle-Invasive Bladder Cancer: Results of a Pilot Phase II Study.

PURPOSE: Reduced quality of life after cystectomy has made bladder preservation a popular research topic for muscle-invasive bladder cancer (MIBC). Previous research has indicated significant tumor downstaging after neoadjuvant chemotherapy (NAC). However, maximal transurethral resection of bladder tumor (TURBT) was performed before NAC to define the pathology, impacting the real evaluation of NAC. This research aimed to assess real NAC efficacy without interference from TURBT and apply combined modality therapies guided by NAC efficacy. MATERIALS AND METHODS: Patients with cT2-4aN0M0 MIBC were confirmed by cystoscopic biopsy and imaging. NAC efficacy was assessed by imaging, urine cytology, and cystoscopy with multidisciplinary team discussion. Definite responders (≤ T1) underwent TURBT plus concurrent chemoradiotherapy. Incomplete responders underwent radical cystectomy or partial cystectomy if feasible. The primary endpoint was the bladder preservation rate. RESULTS: Fifty-nine patients were enrolled, and the median age was 63 years. Patients with cT3-4 accounted for 75%. The median number of NAC cycles was three. Definite responders were 52.5%. The complete response (CR) was 10.2%, and 59.3% of patients received bladder-sparing treatments. With a median follow-up of 44.6 months, the 3-year overall survival (OS) was 72.8%. Three-year OS and relapse-free survival were 88.4% and 60.0% in the bladder-sparing group but only 74.3% and 37.5% in the cystectomy group. The evaluations of preserved bladder function were satisfactory. CONCLUSION: After stratifying MIBC patients by NAC efficacy, definite responders achieved a satisfactory bladder-sparing rate, prognosis, and bladder function. The CR rate reflected the real NAC efficacy for MIBC. This therapy is worth verifying through multicenter research.

Three-component reactions of isochromenylium tetrafluoroborates via non-classical [4+2]-intermediates: mild one-step metal-free synthesis of functionalized dihydronaphthalenes and tetrahydronaphthalenes.

Two novel types of elegant three-component reactions of stable isochromenylium tetrafluoroborates (ICTBs) have been developed under mild metal-free conditions in this work. Mechanistically, these reactions are commonly initiated by a [4+2]-cycloaddition between the non-classical isochromenylium diene and the aldehyde-enol, and terminated by the following addition of weak nucleophiles, including nitriles or the second equivalent of aldehydes, in a one-pot fashion. The developed methodologies exhibit excellent chemoselectivity, regioselectivity, and diastereoselectivity, and provide a new convenient access to functionalized dihydronaphthalenes and tetrahydronaphthalenes.

Construction of multiring frameworks by metal-free cascade reactions of stable isochromenylium tetrafluoroborate.

Efficient methodologies for constructing several multiring frameworks have been developed utilizing the cascade reactions of air-stable isochromenylium tetrafluoroborates with olefins. Successive additions of two equivalents of styrene-type olefins to isochromenylium tetrafluoroborate (ICTB) 1 have been observed and their mechanisms were proposed and discussed. Intramolecular capture of the early stage cationic intermediates by predevised heteroatoms or Friedel-Crafts donors provided two different types of bridged-ring systems.

Transformation of reactive isochromenylium intermediates to stable salts and their cascade reactions with olefins.

Transformation of reactive isochromenylium intermediates to the corresponding storable and stable reagents has been achieved, and a number of isochromenylium tetrafluoroborates (ICTBs, 1) have been conveniently prepared and characterized. Direct metal-free treatment of isochromenylium tetrafluoroborate 1a with olefins afforded a variety of polycyclic frameworks 4 via mild cascade reactions. Starting from the prefunctionalized o-alkynylbenzaldehydes, a one-pot metal-free procedure of intramolecular cascade annulation to 2,3-dihydrophenanthren-4(1H)-one derivatives was also developed.