Comprehensive consideration of multiple determinants from evidence to recommendations in guidelines for most traditional Chinese medicine was suboptimal: a systematic review.

BACKGROUND: The overall comprehensive consideration of the factors influencing the recommendations in the traditional Chinese medicine (TCM) guidelines remains poorly studied. This study systematically evaluate the factors influencing recommendations formation in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) clinical practice guidelines (CPGs) and TCM CPGs. METHODS: This was a methodological review in which we searched six databases and multiple related websites. The GRADE CPGs were identified as the guidelines developed by the GRADE Working Group or the two Co-Chairs. For the TCM CPGs, we randomly selected guidelines that were published by the TCM or integrative medicine academic societies from China mainland (published by the TCM or integrative medicine academic societies of China mainland). Two reviewers independently screened and extracted data. We included CPGs published in 2018-2022. We extracted information on the influencing factors of evidence to recommendation and conducted the analyses using descriptive statistics and calculated the proportion of relevant items by IBM SPSS Statistics and Microsoft Excel to compare the differences between the GRADE CPGs and the TCM CPGs. RESULTS: Forty-five GRADE CPGs (including 912 recommendations) and 88 TCM CPGs (including 2452 recommendations) were included. TCM recommendations mainly considered the four key determinants of desirable anticipated effects, undesirable anticipated effects, balance between desirable and undesirable effects, certainty of evidence, with less than 20% of other dimensions. And TCM CPGs presented more strong recommendations (for or against) and inappropriate discordant recommendations than GRADE CPGs. GRADE CPGs were more comprehensive considered about the factors affecting the recommendations, and considered more than 70% of all factors in the evidence to recommendation. CONCLUSIONS: The TCM CPGs lack a comprehensive consideration of multiple influencing determinants from evidence to recommendations. In the future, the correct application of the GRADE approaches should be emphasized.

BRD4 Inhibition Suppresses Senescence and Apoptosis of Nucleus Pulposus Cells by Inducing Autophagy during Intervertebral Disc Degeneration: An In Vitro and In Vivo Study.

Intervertebral disc degeneration (IDD) is the most common chronic skeletal muscle degeneration disease. Although the underlying mechanisms remain unclear, nucleus pulposus (NP) autophagy, senescence, and apoptosis are known to play a critical role in this process. Previous studies suggest that bromodomain-containing protein 4 (BRD4) promotes senescent and apoptotic effects in several age-related degenerative diseases. It is not known, however, if BRD4 inhibition is protective in IDD. In this study, we explored whether BRD4 influenced IDD. In human clinical specimens, the BRD4 level was markedly increased with the increasing Pfirrmann grade. At the cellular level, BRD4 inhibition prevented IL-1ß-induced senescence and apoptosis of NP cells and activated autophagy via the AMPK/mTOR/ULK1 signaling pathway. Inhibition of autophagy by 3-methyladenine (3-MA) partially reversed the antisenescence and antiapoptotic effects of BRD4. In vivo, BRD4 inhibition attenuated IDD. Taken together, the results of this study showed that BRD4 inhibition reduced NP cell senescence and apoptosis by induced autophagy, which ultimately alleviated IDD. Therefore, BRD4 may serve as a novel potential therapeutic target for the treatment of IDD.

NF-κB signalling pathways in nucleus pulposus cell function and intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a common clinical degenerative disease of the spine. A series of factors, such as inflammation, oxidative stress and mechanical stress, promote degradation of the extracellular matrix (ECM) of the intervertebral discs (IVD), leading to dysfunction and structural destruction of the IVD. Nuclear factor-κB (NF-κB) transcription factor has long been regarded as a pathogenic factor of IDD. Therefore, NF-κB may be an ideal therapeutic target for IDD. As NF-κB is a multifunctional functional transcription factor with roles in a variety of biological processes, a comprehensive understanding of the function and regulatory mechanism of NF-κB in IDD pathology will be useful for the development of targeted therapeutic strategies for IDD, which can prevent the progression of IDD and reduce potential risks. This review discusses the role of the NF-κB signalling pathway in the nucleus pulposus (NP) in the process of IDD to understand pathological NP degeneration further and provide potential therapeutic targets that may interfere with NF-κB signalling for IDD therapy.

Different Types of Double-Level Degenerative Lumber Spondylolisthesis: What Is Different in the Sagittal Plane?

BACKGROUND: Degenerative lumber spondylolisthesis (DLS) is a common orthopedic condition, described as a condition that compared with the lower vertebra, the superior vertebra slides forward or backward in the sagittal plane without accompanying isthmic spondylolisthesis. Information pertaining to different types of double-level DLS is scarce. This study aims to analyze parameters of patients with different types of double-level DLS to provide a reference for guiding surgical treatment and restoring sagittal balance of patients with DLS. METHODS: From January 2014 to January 2020, records of patients with double-level DLS were retrospectively reviewed. Patients with double-level DLS were divided into 3 types: anterior, posterior, and combined; the anterior and combined types were studied. The sagittal spinopelvic parameters included C7 tilt, maximal thoracic kyphosis, maximal lumbar lordosis (LLmax), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). After descriptive analysis, demographic and radiographic data were compared. RESULTS: Forty and 18 patients were included in the anterior and combined type groups, respectively. Both groups had different levels of chronic low back pain, but the incidence of radiating leg pain and neurogenic claudication was significantly higher in the anterior type. Oswestry Disability Index and visual analog scale low back scores were also higher in the anterior type. In the anterior type, C7 tilt (7.14 ± 2.15 vs. 5.41 ± 2.28, P = 0.007), LLmax (50.02 ± 14.76 vs. 36.96 ± 14.56, P = 0.003), PI (68.28 ± 9.16 vs. 55.53 ± 14.19, P < 0.001), PT (28.68 ± 7.31 vs. 19.38 ± 4.70, P < 0.001), and PT/PI (42.45 ± 11.22 vs. 36.04 ± 9.87, P = 0.041) were significantly higher. In the anterior type, PI correlated positively with LLmax (r = 0.59) and SS (r = 0.71). LLmax and SS (r = 0.65) had a positive correlation. PT/PI and SS (r = -0.77) had a negative correlation. In the combined type, PI correlated positively with LLmax (r = 0.61) and SS (r = 0.88), and PT/PI correlated negatively with SS (r = -0.81). CONCLUSIONS: In patients with double-level DLS, the sagittal spinopelvic parameters differed between the anterior and combined types. Overall, spinal surgeons should focus on correcting sagittal deformities, relieving postoperative clinical symptoms, and improving quality of life during fusion surgery.

Sirtuins and intervertebral disc degeneration: Roles in inflammation, oxidative stress, and mitochondrial function.

Intervertebral disc degeneration (IDD) is one of the main causes of low back pain, which seriously reduces the quality of life of patients and places a heavy economic burden on their families. Cellular senescence is considered to be an important factor leading to IDD, and inflammatory response, oxidative stress, and mitochondrial dysfunction are closely related to intervertebral disc (IVD) senescence. Therefore, inhibition of the inflammatory response and oxidative stress, along with maintaining mitochondrial function, may be useful in treating IDD. The sirtuins are a family of evolutionarily conserved nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases, which are the major molecules mediating life extension or delay of aging-related diseases. The sirtuin protein family consist of seven members (SIRT1 - 7), which are mainly involved in various aging-related diseases by regulating inflammation, oxidative stress, and mitochondrial function. Among them, SIRT1, SIRT2, SIRT3, and SIRT6 are closely related to IDD. In addition, some activators of sirtuin proteins, such as resveratrol, melatonin, magnolol, 1,4-dihydropyridine (DHP), SRT1720, and nicotinamide mononucleotide (NMN), have been evaluated in preclinical studies for their effects in preventing IDD. This review described the biological functions of sirtuins and the important roles of SIRT1, SIRT2, SIRT3, and SIRT6 in IDD by regulating oxidative stress, inflammatory response, and mitochondrial function. In addition, we introduce the status of some sirtuin activators in IDD preclinical studies. This review will provide a background for further clarification of the molecular mechanism underlying IDD and the development of potential therapeutic drugs.

An Ensemble Strategy to Predict Prognosis in Ovarian Cancer Based on Gene Modules.

Due to the high heterogeneity and complexity of cancer, it is still a challenge to predict the prognosis of cancer patients. In this work, we used a clustering algorithm to divide patients into different subtypes in order to reduce the heterogeneity of the cancer patients in each subtype. Based on the hypothesis that the gene co-expression network may reveal relationships among genes, some communities in the network could influence the prognosis of cancer patients and all the prognosis-related communities could fully reveal the prognosis of cancer patients. To predict the prognosis for cancer patients in each subtype, we adopted an ensemble classifier based on the gene co-expression network of the corresponding subtype. Using the gene expression data of ovarian cancer patients in TCGA (The Cancer Genome Atlas), three subtypes were identified. Survival analysis showed that patients in different subtypes had different survival risks. Three ensemble classifiers were constructed for each subtype. Leave-one-out and independent validation showed that our method outperformed control and literature methods. Furthermore, the function annotation of the communities in each subtype showed that some communities were cancer-related. Finally, we found that the current drug targets can partially support our method.