Arthroscopic Extra-articular Ulnar Nerve Release in the Setting of Stiff Elbow.

Elbow stiffness can severely affect a patient's quality of life. If conservative treatment is ineffective, surgical treatment including open or arthroscopic release could be applied. With the advantages of being minimally invasive, reducing pain and scars, accelerating early rehabilitation, and so on, arthroscopic release has increased in popularity compared with open surgery over the years, whereas limiting factors such as the close proximity of the neurovasculature to the working field and narrow working space still have to be faced by the elbow arthroscopist, with an increasing risk of iatrogenic injury with portal creation and operations adjacent to the nerves and vessels. When elbow arthritis occurs concomitantly with cubital tunnel syndrome, osteophytes on the medial ridge of the olecranon and trochlea occur as obstacles to the elbow extending or the posterior bundle of the medial collateral ligament has to be released for extension contractures, and open procedures for the medial gutter are routinely performed. To reduce the risk of injury and produce even less scar tissue, we present a surgical technique applicable to posteromedial elbow pathology by 2 medial portals. Through this technique, the entire course of the ulnar nerve is exposed and released under arthroscopy, with the ulnar nerve retracted medially, and medial gutter osteophytectomy and soft-tissue release can freely proceed.

Arthroscopic Medial Bi-portal Extra-articular Debridement for Recalcitrant Medial Epicondylitis.

Medial epicondylitis, or golfer's elbow, is characterized by pain and tenderness at the tendon insertion points of the pronator teres and flexor carpi radialis. Conservative treatment is sufficient for most patients, whereas surgical treatment is the best choice for intractable medial epicondylitis. With open surgery or arthroscopic surgery, good clinical results have been reported. However, there is still no consensus on which surgical technique is more ideal. We describe our technique of arthroscopic medial bi-portal extra-articular debridement, which is a safe and effective technique that allows more accurate debridement and maximum protection of the ulnar nerve while reducing surgical scars, relieving postoperative pain, reducing the probability of elbow infection and ankylosis, and shortening the recovery time.

Luteolin rescues postmenopausal osteoporosis elicited by OVX through alleviating osteoblast pyroptosis via activating PI3K-AKT signaling.

BACKGROUND: Recently, osteoblast pyroptosis has been proposed as a potential pathogenic mechanism underlying osteoporosis, although this remains to be confirmed. Luteolin (Lut), a flavonoid phytochemical, plays a critical role in the anti-osteoporosis effects of many traditional Chinese medicine prescriptions. However, its protective impact on osteoblasts in postmenopausal osteoporosis (PMOP) has not been elucidated. PURPOSE: This research aimed to determine the effect of Lut in ameliorating PMOP by alleviating osteoblast pyroptosis and sustaining osteogenesis. STUDY DESIGN: This research was designed to investigate the novel mechanism of Lut in alleviating PMOP both in cell and animal models. METHODS: Ovariectomy-induced PMOP models were established in mice with/without daily gavaged of 10 or 20 mg/kg body weight Lut. The impact of Lut on bone microstructure, metabolism and oxidative stress was evaluated with 0.104 mg/kg body weight Estradiol Valerate Tablets daily gavaged as positive control. Network pharmacological analysis and molecular docking were employed to investigate the mechanisms of Lut in PMOP treatment. Subsequently, the impacts of Lut on the PI3K/AKT axis, oxidative stress, mitochondria, and osteoblast pyroptosis were assessed. In vitro, cultured MC3T3-E1(14) cells were exposed to H2O2 with/without Lut to examine its effects on the PI3K/AKT signaling pathway, osteogenic differentiation, mitochondrial function, and osteoblast pyroptosis. RESULTS: Our findings demonstrated that 20 mg/kg Lut, similar to the positive control drug, effectively reduced systemic bone loss and oxidative stress, and enhanced bone metabolism induced by ovariectomy. Network pharmacological analysis and molecular docking indicated that the PI3K/AKT axis was a potential target, with oxidative stress response and nuclear membrane function being key mechanisms. Consequently, the effects of Lut on the PI3K/AKT axis and pyroptosis were investigated. In vivo data revealed that the PI3K/AKT axis was deactivated following ovariectomy, and Lut restored the phosphorylation of key proteins, thereby reactivating the axis. Additionally, Lut alleviated osteoblast pyroptosis and mitochondrial abnormalities induced by ovariectomy. In vitro, Lut intervention mitigated the inhibition of the PI3K/AKT axis and osteogenesis, as well as H2O2-induced pyroptosis. Furthermore, Lut attenuated ROS accumulation and mitochondrial dysfunction. The effects of Lut, including osteogenesis restoration, anti-pyroptosis, and mitochondrial maintenance, were all reversed with LY294002 (a PI3K/AKT pathway inhibitor). CONCLUSION: In summary, Lut could improve mitochondrial dysfunction, alleviate GSDME-mediated pyroptosis and maintain osteogenesis via activating the PI3K/AKT axis, offering a new therapeutic strategy for PMOP.

Unravelling cancer subtype-specific driver genes in single-cell transcriptomics data with CSDGI.

Cancer is known as a heterogeneous disease. Cancer driver genes (CDGs) need to be inferred for understanding tumor heterogeneity in cancer. However, the existing computational methods have identified many common CDGs. A key challenge exploring cancer progression is to infer cancer subtype-specific driver genes (CSDGs), which provides guidane for the diagnosis, treatment and prognosis of cancer. The significant advancements in single-cell RNA-sequencing (scRNA-seq) technologies have opened up new possibilities for studying human cancers at the individual cell level. In this study, we develop a novel unsupervised method, CSDGI (Cancer Subtype-specific Driver Gene Inference), which applies Encoder-Decoder-Framework consisting of low-rank residual neural networks to inferring driver genes corresponding to potential cancer subtypes at the single-cell level. To infer CSDGs, we apply CSDGI to the tumor single-cell transcriptomics data. To filter the redundant genes before driver gene inference, we perform the differential expression genes (DEGs). The experimental results demonstrate CSDGI is effective to infer driver genes that are cancer subtype-specific. Functional and disease enrichment analysis shows these inferred CSDGs indicate the key biological processes and disease pathways. CSDGI is the first method to explore cancer driver genes at the cancer subtype level. We believe that it can be a useful method to understand the mechanisms of cell transformation driving tumours.

AAFL: automatic association feature learning for gene signature identification of cancer subtypes in single-cell RNA-seq data.

Single-cell RNA-sequencing (scRNA-seq) technologies have enabled the study of human cancers in individual cells, which explores the cellular heterogeneity and the genotypic status of tumors. Gene signature identification plays an important role in the precise classification of cancer subtypes. However, most existing gene selection methods only select the same informative genes for each subtype. In this study, we propose a novel gene selection method, automatic association feature learning (AAFL), which automatically identifies different gene signatures for different cell subpopulations (cancer subtypes) at the same time. The proposed AAFL method combines the residual network with the low-rank network, which selects genes that are most associated with the corresponding cell subpopulations. Moreover, the differential expression genes are acquired before gene selection to filter the redundant genes. We apply the proposed feature learning method to the real cancer scRNA-seq data sets (melanoma) to identify cancer subtypes and detect gene signatures of identified cancer subtypes. The experimental results demonstrate that the proposed method can automatically identify different gene signatures for identified cancer subtypes. Gene ontology enrichment analysis shows that the identified gene signatures of different subtypes reveal the key biological processes and pathways. These gene signatures are expected to bring important implications for understanding cellular heterogeneity and the complex ecosystem of tumors.

Rasburicase-Induced Falsely Low Measurement of Uric Acid in Tumor Lysis Syndrome: A Report of Two Cases.

Rasburicase, a recombinant urate-oxidase enzyme, can significantly catalyze the oxidation of uric acid to allantoin. It was approved by the US Food and Drug Administration (FDA) to control blood uric acid levels in both pediatric and adult patients especially those with tumor lysis syndrome. It is quite important to realize that rasburicase can continue to be effective ex vivo and cause falsely low results if the blood sample is not contained and transported in ice water immediately. We presented two cases of falsely low measurement of blood uric acid caused by rasburicase and elaborated the proper method for collecting and transporting blood samples from patients using rasburicase.

Zhuanggu Zhitong Capsule alleviates postmenopausal osteoporosis in ovariectomized rats by regulating autophagy through AMPK/mTOR signaling pathway.

Background: Postmenopausal osteoporosis (PMOP) is the most common primary osteoporosis, which is prone to fractures and affect the health and quality of life of the elderly and even shorten their lifetime. Traditional Chinese medicine can not only effectively improve osteoporosis and reduce fracture rate, but also have tonifying and analgesic effects. The purpose of this study was to investigate the effects of Zhuanggu Zhitong (ZGZT) Capsule on autophagy related genes and proteins in PMOP rats, so as to elucidate the molecular mechanism of tonifying deficiency and regulating stasis in the treatment of osteoporosis and analgesia. Methods: The PMOP rat model was established by bilateral oophorectomy, and then the rats were randomly divided into control group, PMOP group, PMOP + ZGZT group and PMOP + E2 group. The changes of mechanical pain threshold of rats were detected by von Frey filaments, and the changes of mechanical pain threshold of rats in each group were compared. Computed tomography (CT) and dual-energy X-ray were used to measure the bone mineral density of lumbar bone tissue. Enzyme-linked immunosorbent assay (ELISA) and tartrate-resistant acid phosphatase (TRAP) staining were used to detect inflammatory factors and bone metabolism related indicators. Hematoxylin-eosin (HE) staining was used to observe the tissue morphology of lumbar vertebra tissue. Western blot (WB) and quantitative polymerase chain reaction (qPCR) were used to detect AMPK/mTOR pathway- and autophagy-related factor expression. Results: ZGZT can effectively restore the bone mineral density (BMD) of PMOP rats, improve the microstructure of lumbar vertebra of PMOP rats, restore the balance of bone metabolism, promote the expression of AMPK and autophagy related factors, inhibit the expression of mTOR and the release of inflammatory factors, and increase the mechanical pain threshold of PMOP rats, so as to effectively improve osteoporosis and relieving osteoporosis pain in PMOP rats. Conclusions: ZGZT affects autophagy by regulating AMPK/mTOR pathway, restores the homeostasis of bone metabolism and inhibits the release of inflammatory factors. Moreover, the regulation of feedback pathways between bone metabolism and inflammatory factors finally plays the role of "bone strengthening" and "pain relieving". ZGZT may be a new treatment for PMOP and relieving osteoporotic pain.

Differences in actionable genomic alterations between brain metastases and non­brain metastases in patients with non­small cell lung cancer.

Brain metastases (BM) have been closely associated with increased morbidity and poor survival outcomes in patients with non­small cell lung cancer (NSCLC). Excluding risk factors in histological subtypes, genomic alterations, including epidermal growth factor receptor mutations and anaplastic lymphoma kinase (ALK) rearrangements have been also regarded as greater risk factors for BM in the aspect of molecular subtypes. In the present study, 69 tumor tissues and 51 peripheral blood samples from patients with NSCLC were analyzed using a hybridization capture­based next­generation sequencing (NGS) panel, including 95 known cancer genes. Among the 90 patients with stage IV NSCLC, 26 cases suffered from BM and 64 cases did not. In total, 174 somatic mutations in 35 mutated genes were identified, and 12 of these genes were concurrently present in the BM group and the non­BM group. Importantly, five mutated genes including ALK, cytidine deaminase (CDA), SMAD family member 4 (SMAD4), superoxide dismutase 2 (SOD2) and Von Hippel­Lindau tumor suppressor (VHL) genes were uniquely detected in the BM group, and they were enriched in the Hippo signaling pathway, pyrimidine metabolism and pantothenate and co­enzyme A (CoA) biosynthesis, as demonstrated using Kyoto Encyclopedia of Genes and Genomes enrichment analysis. RNA polymerase II transcription regulator complex and promyelocytic leukemia nuclear body were the top functional categories according to the Gene Ontology enrichment analysis in the BM group and non­BM group, respectively. Furthermore, 43.33% (13/30) of mutated genes were detected by both tumor tissue deoxyribonucleic acid (DNA) and plasma­derived circulating tumor DNA (ctDNA) in the non­BM group, while this percentage was only limited to 29.41% (5/17) in the BM group. To summarize, significant differences in somatic mutations, somatic interactions, key signaling pathways, functional biological information, and clinical actionability for the therapy of targeted agents were founded between the BM group and the non­BM group, and ctDNA analysis may by applied as a more credible alternative for genomic profiling in patients with advanced NSCLC without BM, due to its higher consistency for genomic profiling between ctDNA analysis and tissue DNA analysis.

Incidence and risk factors of preoperative deep venous thrombosis in closed tibial shaft fracture: a prospective cohort study.

OBJECTIVE: To investigate the preoperative morbidity of deep venous thrombosis (DVT) and predictive risk factors associated with DVT after closed tibial shaft fracture. METHODS: Ultrasonography and blood analyses were performed preoperatively in patients who sustained tibial shaft fracture between October 2014 and December 2018. Univariate analyses were used in the data of demographics, comorbidities, mechanism of injury, concomitant fractures and laboratory biomarkers. Multivariate logistic regression analyses were conducted to determine the independent risk factors associated with DVT. RESULTS: In total, 918 patients with an operatively treated tibial shaft fracture were included, among whom 122 patients had preoperative DVTs, indicating a crude morbidity of 13.3%. Ninety-two of 758 (12.1%) patients with isolated tibial shaft fracture developed DVT, while 30 of 160 (18.8%) patients with concurrent fracture presented with DVT. The average interval between fracture and initial diagnosis of DVT was 3.1 days (median, 2 days), ranging from 0 to 33 days. Among DVT-positive patients, 16 (13.1%) patients presented with proximal DVT and 106 (86.9%) patients had distal DVT. Multivariate logistic regression analysis showed four independent risk factors were significantly correlated to the development of DVT, including increased age (OR = 1.17, p = 0.003), diabetes (OR = 1.99, p = 0.009), serum hydroxybutyrate dehydrogenase > 182 U/L (OR = 1.83, p = 0.008), and delay to DUS (in each day) (OR = 1.13, p < 0.001). CONCLUSION: In the present cohort study, the incidence of DVT was 12.1% in patients with isolated tibial shaft fracture. We suggest individualized risk stratification and early anticoagulation for patients with high risk factors including pre-existing diabetes, HBDH > 182 U/L, delay to DUS and older age. LEVEL OF EVIDENCE: Level III, a prospective cohort study.

Epidemiological Characteristics of Major Joints Fracture-Dislocations.

OBJECTIVE: To describe the epidemiological features of major joints fracture-dislocations between 2015 and 2019. METHODS: This retrospective study enrolled patients with majorintra-articular fracture-dislocations who were treated in the third hospital of Hebei Medical University from January 2015 to December 2019. A total of 582 patients (389 [66.84%] males and 193 [33.16%] females) were identified. The distribution characteristics of intra-articular fracture-dislocations involving shoulder, elbow, wrist, hip, knee, and ankle joints were included. The potential associations between fractures with concomitant dislocations and related factors, such as age, gender and sites were explored. RESULTS: There were 92 cases (15.81%) of shoulder joints, 67 cases (11.51%) of elbow joints, 45 cases (7.73%) of wrist joints, 181 cases (31.10%) of hip joints, 42 cases (7.22%) of knee joints, and 155 cases (26.63%) of ankle joints. The overall male-to-female ratio was 2.02:1.The highest proportion age group of the six types intra-articular fracture-dislocations included the ages 25-34 years. For males, the highest proportion age group was 25-34 years, for females, it was 45-54 years. For male patients, hip was the most common, accounted for 35.48%, but ankle fracture-dislocation was the most common for females, accounted for 30.57%. The highest proportion age group of shoulder fracture-dislocation included the ages 55-64 years(22.83%), with a male to female ratio of 1.24:1. While the age group with the highest risk of elbow, wrist, hip, knee and ankle fracture- dislocation was 25-34 years (28.36%) with a male to female ratio of 2.19:1, 25-34 years (31.11%) with a male to female ratio of 8:1, 45-54 years (27.07%) with a male to female ratio of 3.21:1, 15-24 years (45.24%) with a male to female ratio of 0.75:1, 25-44 years (43.87%) with a male to female ratio of 1.63:1, respectively. The most common site of joint fracture-dislocation in different age groups was corresponding as follows, 0-14 years(elbow), 15-24 years(knee), 25-34 years(hip), 35-44 years(hip), 45-54 years(hip), 55-64 years(ankle), 65-74 years(shoulder), ≥75 years(shoulder). CONCLUSION: Major joints fracture-dislocations were most common in the hip and the least common in the knee, and there were more men than women. Hip was the most common affected joint in men while ankle in women. Age and sex factors can significantly affect the location of intra articular fracture and dislocation. The current study could aid orthopaedic surgeons in a better understanding of this injury and help to implement targeted preventive measures.

Zhuanggu Zhitong Capsule alleviates osteosarcopenia in rats by up-regulating PI3K/Akt/Bcl2 signaling pathway.

BACKGROUND AND AIMS: Osteosarcopenia (OS), characterized by the coexistence of osteoporosis (OP) and sarcopenia (SP), is associated with high morbidity and mortality in the elderly. Nevertheless, its pathogenesis and treatment remain unclear. The aim of this study was to investigate the effect and mechanism of Zhuanggu Zhitong Capsule (ZGZT) in OS rats. METHODS: All the related targets of OS, corresponding targets for bioactive ingredients of ZGZT, intersection targets of ZGZT against OS, and signaling pathways were predicted and analyzed by network pharmacology. Next, a rat OS model was established by ovariectomy (OVX) and injection of dexamethasone (DXM). Rats were then randomly divided into a Control group, a Sham operation group, an OS model group, an OS+ZGZT group, and an OS+E2 group. The drug was given for 12 weeks. During treatment, body weight, forelimb grip and body composition were measured. In addition, bone mineral density (BMD) and micro CT were used to assess the left femur. After treatment, the left femur, left gastrocnemius, and left soleus, as well as uterus, liver, and kidney, were separated and analyzed using Histomorphology, Western blot, and quantitative real-time PCR (qRT-PCR). RESULTS: ZGZT could effectively improve the phenotypes of OS by increasing forelimb grip strength, percentage lean mass of the whole body (SMI) or appendicular lean (RSMI), BMD, levels of bone formation markers, improving the microstructure of femur, and decreasing apoptotic rate in femur and gastrocnemius in OS rats by up-regulating PI3K/Akt/Bcl2 signal pathway. CONCLUSIONS: ZGZT may be a new treatment option for the prevention and treatment of OS.

Prevalence of Preoperative Lower Extremity Deep Vein Thrombosis in Bilateral Calcaneal Fractures.

There are no studies on epidemiologic characteristics of deep vein thrombosis (DVT), when specified at in patients with bilateral calcaneal fractures. This study aimed to address the preoperative DVT in bilateral calcaneal fractures. Between October 2014 and December 2018, adult patients presenting with bilateral calcaneal fractures and having preoperative Duplex ultrasound (DUS) of bilateral lower extremities for detection of DVT were included. Their medical data were collected, with regards to demographics, comorbidities, injury-related data and biomarkers. Baseline characteristics between patients with and without DVT were compared using bivariate tests. The further multivariate logistics regression analysis was conducted to identify independent factors associated with DVT. In total, 258 patients with bilateral calcaneal fractures were included, with 21 (8.1%) having preoperative DVT, diagnosed at 7.7 ± 4.2 days after injury. The prevalence rate of proximal DVT was 1.9% and of distal DVT was 6.2%. Thirty five thrombi were found, with 6 (17.1%) in proximal veins and 29 (82.9%) in distal veins. Nine patients had DVTs in multiple veins, and 2 patients had bilateral DVTs. The multivariate analyses showed history of allergy (odds ratio [OR] = 2.17), concurrent other fractures (OR = 4.53), prolonged time since injury (for each day, OR = 1.16), elevated plasma D-dimer level (≥1.73 vs <1.73 mg/L, OR = 3.74) and reduced albumin level (<34.2 g/L vs ≥34.2 g/L, OR = 2.92) were independent factors associated with DVT. Multiple factors were identified to be associated with DVT and greater consideration should be given to the use of pharmacologic prophylaxis in patients involving these factors, to reduce DVT occurrence.

Age- and Gender-Specific Epidemiologic Characteristics of Major Intra-Articular Fractures: Five-Year Data from a Level 1 Trauma Center.

OBJECTIVE: To investigate the epidemiological characteristics of major intra-articular fractures. METHODS: This retrospective study enrolled patients with major intra-articular fractures who were treated in the Third Hospital of Hebei Medical University from January 2015 to December 2019. A total of 11,084 patients (7,338 [66.20%] males and 3,746 [33.80%] females) meeting the inclusion and exclusion criteria were included. The distribution characteristics of intra-articular fractures involving shoulder, elbow, wrist, hip, knee, ankle, and subtalar joints were identified.The potential associations between fractures and various other factors, such as age, gender, sites, were explored. RESULTS: There were 74 cases (0.67%) of shoulder fractures, 1,941 cases (17.51%) of elbow fractures, 1,155 cases (10.42%) of wrist fractures, 520 cases (4.69%) of hip fractures, 3,118 cases (28.13%) of knee fractures, 2,156 cases (19.45%) of ankle fractures, and 2,120 cases (19.13%) of subtalar fractures. The overall male-to-female ratio was 1.96:1. The highest proportion age group of major intra-articular fractures included the ages 45-54 years. For males, the highest proportion age group was 45-54 years, for females, it was 55-64 years. The knee joint fracture was the most common type, accounting for 28.13%. For male and female patients, knee fractures accounted for 26.19% and 31.93%, respectively, with a male to female ratio of 1.13:1. The proportion of shoulder fractures was the smallest among this investigation, accounting for 0.67%. For male and female patients, shoulder fractures accounted for 0.44% and 1.12%, respectively, with a male to female ratio of 0.76:1. The age group with the highest proportion of shoulder joint fractures was ≥65 year olds (41.89%), with a male to female ratio of 0.76:1. The age group with the highest risk of elbow, wrist, hip, knee, ankle, and subtalar joint fracture was 5-14 year olds (33.59%) with a male to female ratio of 3.29:1, 5-14 year olds (23.98%) with a male to female ratio of 6.91:1, 45-54 year olds (26.92%) with a male to female ratio of 5.67:1, 45-54 year olds (24.60%) with a male to female ratio of 1.68:1, 25-34 year olds (20.36%) with a male to female ratio of 2.30:1, 45-54 year olds (27.41%) with a male to female ratio of 9.02:1, respectively. The most common site of intra-articular fractures in different age groups was corresponding as follows: 0-4 year olds (elbow), 5-14 year olds (elbow), 15-24 year olds (ankle), 25-34 year olds (subtalar joint), 35-44 year olds (subtalar joint), 45-54 year olds (knee), 55-64 year olds (knee), 65-74 year olds (knee), and ≥75 year olds (knee). CONCLUSION: The current study revealed the age- and gender-specific epidemiological characteristics of major intra-articular fractures, providing a basis for clinical evaluation and practices.

Incidence and risks for surgical site infection after closed tibial plateau fractures in adults treated by open reduction and internal fixation: a prospective study.

BACKGROUND: Surgical site infection (SSI) was the most common complication of tibial plateau fracture after open reduction and internal fixation (ORIF). Severe infections even required repeat surgeries, which would cause serious psychological harm to patients and increased the economic burden of treatment. In order to identify the characteristics of the SSI and to avoid the occurrence of SSI, we conducted a prospective study to investigate the incidence and independent risk factors of SSI after ORIF for closed tibial plateau fractures in adults. METHODS: This study was performed at a first-level trauma center. From October 2014 to December 2018, the study subjects were adult patients with closed fractures of the tibial plateau, all of whom underwent open reduction and internal fixation (ORIF) treatment. Finally, a total of 1108 patients were followed up. We collected patient demographics information, surgery-related variables, and indexes from preoperative laboratory examinations. Univariate and multivariate logistic analysis models were used to investigate the potential risk factors. RESULTS: Twenty-five patients (2.3%, 25/1108) developed SSI. A total of 15 of 25 infections (60.0%) were due to Staphylococcus aureus and 3 (12.0%) were due to MRSA. Independent risk factors of SSI identified by multivariate logistic analysis model were bone grafting: autograft (OR 6.38; 95% CI 2.155-18.886; p = 0.001) and allograft (OR 3.215; 95% CI 1.009-10.247; p = 0.048), fracture type (Schartzker V-VI) (OR 8.129; 95% CI 2.961-22.319; p < 0.001), aspartate aminotransferase (>40 U/L) (OR 5.500; 95% CI 2.191-13.807; p < 0.001), white blood cell (>10*109/L) (OR 2.498; 95% CI 1.025-6.092; p = 0.044), and anion gap (>16 mmol/L) (OR 8.194; 95% CI 1.101-60.980). CONCLUSIONS: We should pay enough attention to patients who carried one or more of these factors at admission and adopt more reasonable treatment strategies to reduce or avoid the occurrence of SSI.

Intervertebral disc ageing and degeneration: The antiapoptotic effect of oestrogen.

As an important part of the spinal column, the intervertebral disc (IVD) plays an important role in the intervertebral juncture and spinal movement in general. IVD degeneration (IVDD), which mimics disc ageing but at an accelerated rate, is a common and chronic process that results in severe spinal symptoms, such as lower back pain. It is generally assumed that lower back pain caused by IVDD can also develop secondary conditions, including spinal canal stenosis, spinal segmental instability, osteophyte formation, disc herniation and spinal cord and nerve root compression. Over the past few years, many researchers around the world have widely studied the relevance between oestrogen and IVDD, indicating that oestrogen can effectively alleviate IVDD development by inhibiting the apoptosis of IVD cells. Oestrogen can decrease IVD cell apoptosis in multiple ways, including the inhibition of the inflammatory cytokines IL-1ß and TNF-α, reducing catabolism because of inhibition of matrix metalloproteinases, upregulating integrin α2ß1 and IVD anabolism, activating the PI3K/Akt pathway, decreasing oxidative damage and promoting autophagy. In this article, we perform an overview of the literature regarding the antiapoptotic effect of oestrogen in IVDD.

Fermentation by Multiple Bacterial Strains Improves the Production of Bioactive Compounds and Antioxidant Activity of Goji Juice.

Microorganisms can be used for enhancing flavors or metabolizing functional compounds. The fermented-food-derived bacterial strains comprising Bacillus velezensis, Bacillus licheniformis, and Lactobacillus reuteri mixed with Lactobacillus rhamnosus and Lactobacillus plantarum were used to ferment goji berry (Lycium barbarum L.) juice in this study. The fermentation abilities and antioxidant capacities of different mixtures of multiple strains in goji juice were compared. The results showed that the lactic acid contents increased 9.24-16.69 times from 25.30 ± 0.71 mg/100 mL in goji juice fermented using the SLV (Lactobacillus rhamnosus, Lactobacillus reuteri, and Bacillus velezensis), SZP (Lactobacillus rhamnosus, Lactobacillus plantarum, and Bacillus licheniformis), and SZVP (Lactobacillus rhamnosus, Lactobacillus plantarum, Bacillus velezensis, and Bacillus licheniformis) mixtures, and the protein contents increased 1.31-2.11 times from 39.23 ± 0.67 mg/100 mL. In addition, their contents of volatile compounds increased with positive effects on aroma in the fermented juices. Conversion of the free and bound forms of phenolic acids and flavonoids in juice was influenced by fermentation, and the antioxidant capacity improved significantly. Fermentation enhanced the contents of lactic acid, proteins, volatile compounds, and phenols. The antioxidant capacity was strongly correlated with the phenolic composition.

αvß3 Integrin Is Required for Efficient Infection of Epithelial Cells with Human Adenovirus Type 26.

Human adenoviruses (HAdVs) are being explored as vectors for gene transfer and vaccination. Human adenovirus type 26 (HAdV26), which belongs to the largest subgroup of adenoviruses, species D, has a short fiber and a so-far-unknown natural tropism. Due to its low seroprevalence, HAdV26 has been considered a promising vector for the development of vaccines. Despite the fact that the in vivo safety and immunogenicity of HAdV26 have been extensively studied, the basic biology of the virus with regard to receptor use, cell attachment, internalization, and intracellular trafficking is poorly understood. In this work, we investigated the roles of the coxsackievirus and adenovirus receptor (CAR), CD46, and αv integrins in HAdV26 infection of human epithelial cell lines. By performing different gain- and loss-of-function studies, we found that αvß3 integrin is required for efficient infection of epithelial cells by HAdV26, while CAR and CD46 did not increase the transduction efficiency of HAdV26. By studying intracellular trafficking of fluorescently labeled HAdV26 in A549 cells and A549-derived cell clones with stably increased expression of αvß3 integrin, we observed that HAdV26 colocalizes with αvß3 integrin and that increased αvß3 integrin enhances internalization of HAdV26. Thus, we conclude that HAdV26 uses αvß3 integrin as a receptor for infecting epithelial cells. These results give us new insight into the HAdV26 infection pathway and will be helpful in further defining HAdV-based vector manufacturing and vaccination strategies.IMPORTANCE Adenovirus-based vectors are used today for gene transfer and vaccination. HAdV26 has emerged as a promising candidate vector for development of vaccines due to its relatively low seroprevalence and its ability to induce potent immune responses against inserted transgenes. However, data regarding the basic biology of the virus, like receptor usage or intracellular trafficking, are limited. In this work, we found that efficient infection of human epithelial cell lines by HAdV26 requires the expression of the αvß3 integrin. By studying intracellular trafficking of fluorescently labeled HAdV26 in a cell clone with stably increased expression of αvß3 integrin, we observed that HAdV26 colocalizes with αvß3 integrin and confirmed that αvß3 integrin expression facilitates efficient HAdV26 internalization. These results will allow further improvement of HAdV26-based vectors for gene transfer and vaccination.

Acupuncture for musculoskeletal pain: A meta-analysis and meta-regression of sham-controlled randomized clinical trials.

The aims of this systematic review were to study the analgesic effect of real acupuncture and to explore whether sham acupuncture (SA) type is related to the estimated effect of real acupuncture for musculoskeletal pain. Five databases were searched. The outcome was pain or disability immediately (≤1 week) following an intervention. Standardized mean differences (SMDs) with 95% confidence intervals were calculated. Meta-regression was used to explore possible sources of heterogeneity. Sixty-three studies (6382 individuals) were included. Eight condition types were included. The pooled effect size was moderate for pain relief (59 trials, 4980 individuals, SMD -0.61, 95% CI -0.76 to -0.47; P < 0.001) and large for disability improvement (31 trials, 4876 individuals, -0.77, -1.05 to -0.49; P < 0.001). In a univariate meta-regression model, sham needle location and/or depth could explain most or all heterogeneities for some conditions (e.g., shoulder pain, low back pain, osteoarthritis, myofascial pain, and fibromyalgia); however, the interactions between subgroups via these covariates were not significant (P < 0.05). Our review provided low-quality evidence that real acupuncture has a moderate effect (approximate 12-point reduction on the 100-mm visual analogue scale) on musculoskeletal pain. SA type did not appear to be related to the estimated effect of real acupuncture.

Isolation and Functional Characterization of a Novel Gene Encoding a Dehydration Responsive Element Binding Transcription Factor from Populus euphratica.

Dehydration responsive element binding (DREB) transcription factors (TFs) play a key role in regulating abiotic stress related genes. A new gene (PeDREB2b) encoding an unidentified DRE-binding protein was isolated from 20% PEG6000 treated Populus euphratica Oliv. seedlings by RT-PCR and RACE. Full length of PeDREB2b cDNA was 1110 bp, and an ORF of 870 bp, which encoded 289-amino-acids polypeptide, were included. The deduced amino acid sequence analysis revealed that this protein was a putative AP2/EREBP transcription factor with a conserved AP2/EREBP domain of 64 amino acids and a potential nuclear localization signal (NLS). Based on phylogenetic characterization, PeDREB2b was classified as a member of A-5 group belonged to the DREB family. The PeDREB2b gene is induced by salinization, low temperature, drought and phytohormones GA3, NAA and 6BA, but not by ABA treatment. The fact that the product of PeDREB2b as a DREB transcription factor was verified in our further experiment: the nuclear localization of the gene when it was expressed transiently as a GFP fusion in onion epidermal cells. In addition, PeDREB2b was capable of activating reporter gene expression. To study the salt and drought stress responses for PeDREB2b transgenic Arabidopsis thaliana in detail, integrated physiological, biochemical and genetic approach methods were used. Results indicated that the PeDREB2b gene was over-expressed under stress-inducible rd29A promotor in transgenic plants alleviates the adverse effects of environmental stresses.

Genetic conjugation of components in two pneumococcal fusion protein vaccines enhances paediatric mucosal immune responses.

Streptococcus pneumoniae colonises the upper respiratory tract and can cause pneumonia, meningitis and otitis media. Existing pneumococcal conjugate vaccines are expensive to produce and only protect against 13 of the 90+ pneumococcal serotypes; hence there is an urgent need for the development of new vaccines. We have shown previously in mice that pneumolysin (Ply) and a non-toxic variant (Δ6Ply) enhance antibody responses when genetically fused to pneumococcal surface adhesin A (PsaA), a potentially valuable effect for future vaccines. We investigated this adjuvanticity in human paediatric mucosal primary immune cell cultures. Adenoidal mononuclear cells (AMNC) from children aged 0-15 years (n=46) were stimulated with conjugated, admixed or individual proteins, cell viability and CD4+ T-cell proliferative responses were assessed using flow cytometry and cytokine secretion was measured using multiplex technology. Proliferation of CD4+ T-cells in response to PsaAPly, was significantly higher than responses to individual or admixed proteins (p=0.002). In contrast, an enhanced response to PsaAΔ6Ply compared to individual or admixed proteins only occurred at higher concentrations (p<0.01). Evaluation of cytotoxicity suggested that responses occurred when Ply-induced cytolysis was inhibited, either by fusion or mutation, but importantly an additional toxicity independent immune enhancing effect was also apparent as a result of fusion. Responses were MHC class II dependent and had a Th1/Th17 profile. Genetic fusion of Δ6Ply to PsaA significantly modulates and enhances pro-inflammatory CD4+ T-cell responses without the cytolytic effects of some other pneumolysoids. Membrane binding activity of such proteins may confer valuable adjuvant properties as fusion may assist Δ6Ply to deliver PsaA to the APC surface effectively, contributing to the initiation of anti-pneumococcal CD4+ T-cell immunity.