Xanthohumol relieves arthritis pain in mice by suppressing mitochondrial-mediated inflammation.

Chronic pain is the most common symptom for people who suffer from rheumatoid arthritis and it affects approximately 1% of the global population. Neuroinflammation in the spinal cord induces chronic arthritis pain. In this study, a collagen-induced arthritis (CIA) mice model was established through intradermally injection of type II collagen in complete Freund's adjuvant solution. Following CIA inducement, the paws and ankles of mice were found to swell, mechanical pain and spontaneous pain were induced, and their motor coordination was impaired. The spinal inflammatory reaction was triggered, which presented as severe infiltration of inflammatory cells, and the expression levels of GFAP, IL-1ß, NLRP3, and cleaved caspase-1 increased. Oxidative stress in the spinal cord of CIA mice was manifested as reduced Nrf2 and NDUFB11 expression and SOD activity, and increased levels of DHODH and Cyto-C. At the same time, spinal AMPK activity was decreased. In order to explore the potential therapeutic options for arthritic pain, Xanthohumol (Xn) was intraperitoneally injected into mice for three consecutive days. Xn treatment was found to reduce the number of spontaneous flinches, in addition to elevating mechanical pain thresholds and increasing latency time. At the same time, Xn treatment in the spinal cord reduced NLRP3 inflammasome-mediated inflammation, increased the Nrf2-mediated antioxidant response, and decreased mitochondrial ROS level. In addition, Xn was found to bind with AMPK via two electrovalent bonds and increased AMPK phosphorylation at Thr174. In summary, the findings indicate that Xn treatment activates AMPK, increases Nrf2-mediated antioxidant response, reduces Drp1-mediated mitochondrial dysfunction, suppresses neuroinflammation, and can serve to relieve arthritis pain.

An annotated human blastocyst dataset to benchmark deep learning architectures for in vitro fertilization.

Medical Assisted Reproduction proved its efficacy to treat the vast majority forms of infertility. One of the key procedures in this treatment is the selection and transfer of the embryo with the highest developmental potential. To assess this potential, clinical embryologists routinely work with static images (morphological assessment) or short video sequences (time-lapse annotation). Recently, Artificial Intelligence models were utilized to support the embryo selection procedure. Even though they have proven their great potential in different in vitro fertilization settings, there is still considerable room for improvement. To support the advancement of algorithms in this research field, we built a dataset consisting of static blastocyst images and additional annotations. As such, Gardner criteria annotations, depicting a morphological blastocyst rating scheme, and collected clinical parameters are provided. The presented dataset is intended to be used to train deep learning models on static morphological images to predict Gardner's criteria and clinical outcomes such as live birth. A benchmark of human expert's performance in annotating Gardner criteria is provided.

A randomized, parallel control and multicenter clinical trial of evidence-based traditional Chinese medicine massage treatment VS External Diclofenac Diethylamine Emulgel for the treatment of knee osteoarthritis.

BACKGROUND: Both massage and topically administered NSAIDs are safe and effective treatments for knee osteoarthritis (KOA); however, different massage technique sects in China caused assessment difficulties for the treatment of KOA. In order to standardize the massage techniques and procedures, we organized multi-disciplinary experts in China to acquire an evidence-based traditional Chinese medicine massage treatment of knee osteoarthritis. The purposes of this study will be to provide clinicians a complementary and alternative therapy for patients and to evaluate the efficacy and safety of evidence-based traditional Chinese medicine massage treatment of KOA compared to External Diclofenac Diethylamine Emulgel. METHODS AND DESIGN: A randomized controlled trial in which 300 participants diagnosed with KOA will be recruited and randomly allocated to either the experimental group or the control group in a ratio of 2:1. Two hundred participants will receive evidence-based traditional Chinese medicine massage 2 sessions per week for 10 weeks as the experimental group, and 100 participants will receive External Diclofenac Diethylamine Emulgel 3-4 times per day for 10 weeks as the control group. The patients in the two groups will receive follow-up at two time points at 5 weeks and 10 weeks from the beginning of treatment, respectively. The MRI scans and X-ray will be performed at baseline and at the end of the intervention. The primary outcome will be the changes in the Western Ontario and McMaster Osteoarthritis Index (WOMAC). Secondary outcomes will be measured by the PRO scale for knee osteoarthritis based on the concept of traditional Chinese medicine (Chinese scale for knee osteoarthritis (CSKO)), X-ray evaluation, and MRI scan evaluation. The data of WOMAC and CSKO will be analyzed at the baseline, 5 weeks, and 10 weeks from the beginning of treatment. The data from MRI scans and X-rays will be analyzed at baseline and at the end of the intervention. The significance level sets as 5%. The safety of interventions will be evaluated after each treatment session. DISCUSSION: This study will provide clinicians with much-needed knowledge for the treatment of KOA through a controlled trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800014400 . Registered on 10 January 2018.

A New Surgical Method of U-Shaped Myometrial Excavation and Modified Suture Approach with Uterus Preservation for Diffuse Adenomyosis.

OBJECTIVE: To evaluate the feasibility, safety, and efficacy of a new surgical method of U-shaped myometrial excavation and modified suture approach with uterus preservation for diffuse adenomyosis. METHODS: From January 2012 to December 2014, 198 patients with diffuse adenomyosis were surgically treated using this novel procedure in Zhengzhou Hua-Shan Hospital. Degree of dysmenorrhea, menstrual blood volume, serum CA 125, and uterine size before and at 1 month, 3 months, 6 months, 12 months, and 24 months after surgery were compared. RESULTS: Postoperatively, VAS score of dysmenorrhea, menstrual blood volume, serum CA 125 level, and uterine size significantly decreased at 1 month, 3 months, 6 months, 12 months, and 24 months from presurgical levels (all p < .001), but there were no differences at the follow-up time points. Two patients recurred at 18 months and 23 months after surgery, but both recovered after repeat surgery. Interestingly, 2 other patients recrudesced at 10 months and 12 months after surgery. In addition, only one patient was found to have a postoperative anaemia with fever, conservatively managed without surgery. CONCLUSION: U-shaped myometrial excavation and modified suture approach with uterus preservation is a safe and feasible surgical approach to treat diffuse adenomyosis, with favourable outcomes.

Hsp27: a novel therapeutic target for pediatric M4/M5 acute myeloid leukemia.

Heat shock protein 27 (Hsp27), a member of the heat shock protein (Hsp) family, is critical in the regulation of cancer development, progression and chemotherapy resistance. However, the role of Hsp27 in the pathogenesis of pediatric acute leukemia (AL) remains unknown. In this study, we evaluated the expression levels of Hsp27 in bone marrow samples from 94 children with newly diagnosed acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and 5 leukemia cell lines. Additionally, we transfected a target-specific siRNA duplex against Hsp27 into leukemia cells, and examined the chemosensitivity and cell apoptosis in the response to antitumor drugs. Hsp27 was abundantly expressed in newly diagnosed AML-M4/M5 bone marrow mononuclear cells (BMMCs) and THP-1, OCI/AML-3 leukemia cell lines. Furthermore, its expression was positively correlated with the clinical status in pediatric M4/M5 subtypes. Knockdown of Hsp27 expression increased the chemosensitivity of leukemia cells and the anticancer drug-induced apoptosis. These results support the theory that Hsp27 plays a contributory role in the pathogenesis of pediatric AML-M4/M5. Therefore, Hsp27 may be exploited as a new target for enhancing the efficacy of chemotherapeutic drugs against leukemia.

Mechanical properties of luffa sponge.

The paper presents the first scientific study of the stiffness, strength and energy absorption characteristics of the luffa sponge with a view to using it as an alternative sustainable engineering material for various practical applications. A series of compression tests on luffa sponge columns have been carried out. The stress-strain curves show a near constant plateau stress over a long strain range, which is ideal for energy absorption applications. It is found that the luffa sponge material exhibits remarkable stiffness, strength and energy absorption capacities that are comparable to those of some metallic cellular materials in a similar density range. Empirical formulae have been developed for stiffness, strength, densification strain and specific energy absorption at the macroscopic level. A comparative study shows that the luffa sponge material outperforms a variety of traditional engineering materials.

Neuritin is expressed in Schwann cells and down-regulated in apoptotic Schwann cells under hyperglycemia.

We aimed to explore neuritin expression in Schwann cells under different glucose conditions. Expression of neuritin at the levels of transcription and translation in purified Schwann cells was detected and measured using reverse transcriptase (RT) (quantitative) polymerase chain reaction (PCR) and western blot. Apoptosis of Schwann cells was measured by flow cytometry using Fluorescence Activated Cell Sorter (FACS) analysis and caspase fluorometric assay. Neuritin mRNA and protein were detected in cultured primary Schwann cells. Neuritin was identified as cell membrane form of protein and predominately as secreted or solube form of protein. Neuritin was significantly lower in 150 mM glucose condition, and more significantly lower in 300 mM glucose, than 5.6 mM glucose condition at 36 hours and especially at 48 hours of the culture, respectively (P < 0.05-0.01). In contrast to 5.6 mM glucose, obvious apoptosis of Schwann cells was demonstrated at 42 hours in 300 mM glucose condition and at 48 hours in 150 mM glucose, respectively (P < 0.05-0.01). Neuritin and apoptosis were correlated in a power regression (P < 0.01). 5.6 mM glucose cultured cells did not show these obvious changes during the experiment. It is concluded that neuritin mRNA and protein were expressed and down-regulated in Schwann cells under high-glucose concentration and the down-regulation may contribute to apopotosis of Schwann cells.