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Objective: To investigate the characteristics of gene mutations in angioimmunoblastic T-cell lymphoma (AITL). Methods: Seventy-five AITL cases diagnosed at the Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from June 2021 to June 2023 were included. Their formalin-fixed and paraffin-embedded or fresh tissues were subject to targeted next generation sequencing (NGS). The sequencing data was collected, and the distribution and type of gene mutations were analyzed. Results: 492 potential driver mutations were identified in 74 out of the 84 genes. Targeted sequencing data for the 75 AITL patients showed that the genes with mutation frequencies of ≥10% were TET2 (89.3%), RHOA (57.3%), IDH2 (37.3%), DNMT3A (36.0%), KMT2C (21.3%), PLCG1 (12.0%), and KDM6B (10.7%). There were significant co-occurrence relationships between TET2 and RHOA, TET2 and IDH2, and RHOA and IDH2 gene mutations (P<0.05), respectively, while TET2 and KDM6B gene mutations were mutually exclusive (P<0.05). Conclusions: The study reveals the mutational characteristics of AITL patients using NGS technology, which would provide insights for molecular diagnosis and targeted therapy of AITL.
Subject(s)
Humans , Lymphoma, T-Cell/pathology , China , Immunoblastic Lymphadenopathy/diagnosis , Mutation , Mutation Rate , Jumonji Domain-Containing Histone Demethylases/geneticsABSTRACT
Objective:To analyze the clinical efficacy of internal fixation and prosthesis revision in the treatment of periprosthesis fracture after total knee arthroplasty.Methods:A total of 35 patients (35 knees) with periprosthetic fractures after total knee arthroplasty were retrospectively analyzed from January 2008 to January 2022 in the Department of Orthopaedics, West China Hospital, Sichuan University, including 13 males and 22 females, aged 71.4±4.1 years (range, 62-81 years). Left knee 19 cases, right knee 16 cases. There were 20 cases of Rorabeck type II and 15 cases of Rorabeck type III. The initial replacement was performed using a fixed platform post-stabilized knee prosthesis, which was fixed with bone cement. Patients with Rorabeck type II were treated with internal fixation alone (internal fixation group) and patients with Rorabeck type III underwent revision with replacement prosthesis (revision group). The Hospital for Special Surgery (HSS) score, range of motion (ROM) of knee joint, alignment of lower extremity and incidence of postoperative complications were compared between the two groups.Results:All patients successfully completed the operation and were followed up for 5.2±3.6 years (range, 1-12 years). Intraoperative blood loss was 680±102 ml (range, 420-1100 ml). The operative time in the internal fixation group was 105±17 min, which was less than 140±21 min in the revision group, and the difference was statistically significant ( t=-5.450, P<0.001). There was no complication of nerve or blood vessel injury during the operation. Five cases in the internal fixation group had unsatisfactory lower extremity force lines (>3° deviation from normal) after surgery, and all lower extremity force lines in the revision group were satisfied, and the difference in the satisfaction rate of lower extremity force lines between the two groups was not statistically significant ( P=0.057). The fracture healing time, knee ROM and HSS scores at the last follow-up were 5.1±1.3 months, 86°±5° and 84±5 in the internal fixation group and 4.8±1.5 months, 83°±6° and 82±4 in the revision group. One case in the revision group was diagnosed postoperatively with periprosthetic infection with pathogen culture suggestive of Candida albicans, recurrent anterior knee sinus tracts and patellar ectasia, which progressed to osteomyelitis, and mid-thigh amputation was performed 1 year after revision. Conclusion:The stability of prosthesis is an important reference for the treatment of periprosthetic fractures after total knee arthroplasty. Strong internal fixation in patients with unloosened prosthesis and revision with replacement of prosthesis in patients with loose prosthesis can achieve good knee joint function.
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Objective:To explore any effect of on the limb and cardiopulmonary functioning of stroke survivors of combining new Bobath technique with cardiopulmonary rehabilitation.Methods:A total of 160 stroke survivors with limb disorders were randomly divided into an observation group and a control group, each of 80. Both groups were given routine rehabilitation and the new version of Bobath training, but the observation group was additionally provided with 12 weeks of cardiopulmonary rehabilitation. Before and after the treatment the limb functioning of both groups was evaluated along with their ability in the activities of daily living and the recovery of damaged nerve function, using the simplified Fugl-Meyer (FMA) motor function scoring, the modified Barthel index (MBI) and the Chinese stroke scale (CSS). Peak oxygen uptake (VO 2peak), peak metabolic equivalent (METpeak), peak heart rate (HRpeak) and anaerobic thresholds (ATs) were documented. Results:After the treatment the average FMA, MBI and CSS scores and cardiopulmonary indexes had improved significantly in both groups. All were then significantly better in the observation group than in the control group.Conclusions:Combining the new Bobath technique with cardiopulmonary rehabilitation can significantly improve the limb and cardiopulmonary functioning of stroke survivors, as well as their skill in the activities of daily living and the recovery of the damaged nerve functionality. This combination is therefore worthy of clinical promotion and application.
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BACKGROUND@#Patellofemoral joint (PFJ) degeneration has traditionally been regarded as a contraindication to unicompartmental knee arthroplasty (UKA). More recently, some researchers have proposed that PFJ degeneration can be ignored in medial UKA, and others have proposed that this change should be reviewed in PFJ degenerative facets and severity. This study aimed to systematically evaluate the effect of PFJ degeneration on patient-reported outcome measures (PROMs) and revision rates after medial UKA.@*METHODS@#Electronic databases (PubMed, Embase, Web of Science, etc.) were searched for studies assessing the influence of PFJ degeneration on medial UKA. A random-effects meta-analysis was conducted for the Oxford knee score (OKS), Knee society score (KSS), and revision rates and stratified by PFJ degenerative facets (medial/lateral/trochlear/unspecified), severe PFJ degeneration (bone exposed), and bearing type (mobile/fixed). Heterogeneity was assessed by the Cochran Q test statistic and chi-squared tests with the I-squared statistic.@*RESULTS@#A total of 34 articles with 7007 knees (2267 with PFJ degeneration) were included (5762 mobile-bearing and 1145 fixed-bearing and 100 unspecified). Slight to moderate degenerative changes in the medial and trochlear facets did not decrease the OKS and KSS, and only lateral facets significantly decreased the OKS (mean difference [MD] = -2.18, P < 0.01) and KSS (MD = -2.61, P < 0.01). The severity degree of PFJ degeneration had no additional adverse effect on the OKS, KSS, or revision rates. For mobile-bearing UKA, only lateral PFJ degeneration significantly decreased the OKS (MD = -2.21, P < 0.01) and KSS (MD = -2.44, P < 0.01). For fixed-bearing UKA, no correlation was found between PROMs/revision rates and PFJ degeneration.@*CONCLUSION@#For medial mobile-bearing UKA, slight to moderate degenerative changes in the PFJ, except lateral facet, did not compromise PROMs or revision rates. For medial fixed-bearing UKA, although it might not be conclusive enough, PROMs or revision rates were not adversely affected by PFJ degeneration (regardless of the facet).
Subject(s)
Humans , Arthroplasty, Replacement, Knee , Patellofemoral Joint/surgery , Treatment Outcome , Osteoarthritis, Knee/surgery , Knee Prosthesis , Bone Diseases , Knee Joint/surgery , Retrospective StudiesABSTRACT
Sports fatigue of the lower limbs is one of the important factors affecting sports performance. How to improve the anti-fatigue ability of the lower limbs during endurance exercise is the focus of the research field of human sports biomechanics. This study systematically reviewed the relevant literature on transcranial direct current stimulation (tDCS) intervention on lower limb endurance performance, summarized the effect of tDCS on lower limb endurance performance, and analyzed the influencing factors and potential mechanisms. The results showed that: tDCS intervention has a significant effect on the endurance performance of the whole lower limbs, but there is no unified conclusion on the effect on the endurance performance of the knee joint. The researchers deem that tDCS can increase the excitability of the primary motor cortex and reduce the activation of the supplementary motor area and the premotor area to producing a lower rating of perceived exertion, but cannot affect the perception of exercise-induced pain, and stimulation protocols varied across studies, which may be partly responsible. This study can provide a theoretical basis for exploring the central mechanism of tDCS to improve endurance performance, formulating rehabilitation and sports training programsfor different groups of people, and developing new stimulation equipment to enhance the human body’s anti fatigue ability.
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BACKGROUND@#Despite the advent of innovative knee prosthesis design, a consistent first-option knee implant design in total knee arthroplasty (TKA) remained unsettled. This study aimed to compare the clinical effects among posterior-stabilized (PS), cruciate-retaining (CR), bi-cruciate substituting (BCS), and bi-cruciate retaining designs for primary TKA.@*METHODS@#Electronic databases were systematically searched to identify eligible randomized controlled trials (RCTs) and cohort studies from inception up to July 30, 2021. The primary outcomes were the range of knee motion (ROM), and the secondary outcomes were the patient-reported outcome measures (PROMs) and complication and revision rates. Confidence in evidence was assessed using Confidence in Network Meta-Analysis. The Bayesian network meta-analysis was performed for synthesis.@*RESULTS@#A total of 15 RCTs and 18 cohort studies involving 3520 knees were included. The heterogeneity and inconsistency were acceptable. There was a significant difference in ROM at the early follow-up when PS was compared with CR (mean difference [MD] = 3.17, 95% confidence interval [CI] 0.07, 7.18) and BCS was compared with CR (MD = 9.69, 95% CI 2.18, 17.51). But at the long-term follow-up, there was no significant difference in ROM in any one knee implant compared with the others. No significant increase was found in the PROMs and complication and revision rates at the final follow-up time.@*CONCLUSIONS@#At early follow-up after TKA, PS and BCS knee implants significantly outperform the CR knee implant in ROM. But in the long run, the available evidence suggests different knee prostheses could make no difference in clinical outcomes after TKA with extended follow-up.
Subject(s)
Humans , Arthroplasty, Replacement, Knee , Posterior Cruciate Ligament/surgery , Network Meta-Analysis , Osteoarthritis, Knee/surgery , Knee Joint/surgery , Knee Prosthesis , Range of Motion, ArticularABSTRACT
METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Subject(s)
Animals , Mice , Methylation , Chromatin , Histones/metabolism , RNA, Messenger/genetics , Methyltransferases/metabolism , RNA/metabolismABSTRACT
OBJECTIVE@#Using the mono-energy reconstruction images and X-ray films to investigate whether the ABG Ⅱ short-stem could improve the filling ratio, stability, and alignment in the Dorr type C femur, compared with the Corail long-stem.@*METHODS@#Among patients who were with Dorr type C femurs and treated with total hip arthroplasty between January 2006 and March 2012, 20 patients with a Corail long-stem (Corail group) and 20 patients with an ABG Ⅱ short-stem (ABG Ⅱ group) were randomly selected. The differences in gender, age, body mass index, and preoperative diagnoses between the two groups were not significant ( P>0.05). The ABG Ⅱ group was with a mean follow-up of 142 months (range, 102-156 months), and the Corail group was with a mean follow-up of 107 months (range, 91-127 months). There was no significant difference in the Harris score and subjective satisfaction score between the two groups at last follow-up ( P>0.05). At last follow-up, dual-energy CT scans with mono-energy image reconstruction were used to calculate the prosthetic filling ratio and to measure the alignment of the prosthesis in the coronal and sagittal positions. Stability assessment was performed based on X-ray films, and the subsidence distance was measured using EBRA-FCA software.@*RESULTS@#X-ray film observation showed that the prostheses in the two groups were stable and no signs of loosening was found. The incidence of pedestal sign was significantly lower in the ABGⅡ group than in the Corail group ( P<0.05), and the incidence of heterotopic ossification was significantly higher in the ABGⅡ group than in the Corail group ( P<0.05). The subsidence distance of femoral stem in ABG Ⅱ group was significantly greater than that in Corail group ( P<0.05), and the subsidence speed of femoral stem in ABG Ⅱ group was also greater than that in Corail group, but the difference was not significant ( P>0.05). The overall prosthesis filling ratio was significantly higher in the ABG Ⅱ group than in the Corail group ( P<0.05), while the coronal filling ratio at the lesser trochanter, 2 cm below the lesser trochanter, and 7 cm below the lesser trochanter were not significant ( P>0.05). The results of prosthesis alignment showed that there was no significant difference in the sagittal alignment error value and the incidence of coronal and sagittal alignment error >3° between the two groups ( P>0.05), while the coronal alignment error value in the ABG Ⅱ group was significantly greater than that in the Corail group ( P<0.05).@*CONCLUSION@#Although the ABG Ⅱ short-stem avoids the distal-proximal mismatch of the Corail long-stem in the Dorr type C femur and thus achieves a higher filling ratio, it does not appear to achieve better alignment or stability.
Subject(s)
Humans , Arthroplasty, Replacement, Hip/methods , Femur/surgery , Hip Prosthesis , Lower Extremity/surgery , Prosthesis Design , Retrospective StudiesABSTRACT
OBJECTIVE@#To summarize the role of chondrocyte mitochondrial homeostasis imbalance in the pathogenesis of osteoarthritis (OA) and analyze its application prospects.@*METHODS@#The recent literature at home and abroad was reviewed to summarize the mechanism of mitochondrial homeostasis imbalance, the relationship between mitochondrial homeostasis imbalance and the pathogenesis of OA, and the application prospect in the treatment of OA.@*RESULTS@#Recent studies have shown that mitochondrial homeostasis imbalance, which is caused by abnormal mitochondrial biogenesis, the imbalance of mitochondrial redox, the imbalance of mitochondrial dynamics, and damaged mitochondrial autophagy of chondrocytes, plays an important role in the pathogenesis of OA. Abnormal mitochondrial biogenesis can accelerate the catabolic reaction of OA chondrocytes and aggravate cartilage damage. The imbalance of mitochondrial redox can lead to the accumulation of reactive oxygen species (ROS), inhibit the synthesis of extracellular matrix, induce ferroptosis and eventually leads to cartilage degradation. The imbalance of mitochondrial dynamics can lead to mitochondrial DNA mutation, decreased adenosine triphosphate production, ROS accumulation, and accelerated apoptosis of chondrocytes. When mitochondrial autophagy is damaged, dysfunctional mitochondria cannot be cleared in time, leading to ROS accumulation, which leads to chondrocyte apoptosis. It has been found that substances such as puerarin, safflower yellow, and astaxanthin can inhibit the development of OA by regulating mitochondrial homeostasis, which proves the potential to be used in the treatment of OA.@*CONCLUSION@#The mitochondrial homeostasis imbalance in chondrocytes is one of the most important pathogeneses of OA, and further exploration of the mechanisms of mitochondrial homeostasis imbalance is of great significance for the prevention and treatment of OA.
Subject(s)
Humans , Reactive Oxygen Species/metabolism , Chondrocytes/metabolism , Osteoarthritis/metabolism , Homeostasis , Mitochondria/metabolism , Cartilage, Articular/metabolismABSTRACT
OBJECTIVE@#To review the research progress of mitochondrial dynamics mediated by optic atrophy 1 (OPA1) in skeletal system diseases.@*METHODS@#The literatures about OPA1-mediated mitochondrial dynamics in recent years were reviewed, and the bioactive ingredients and drugs for the treatment of skeletal system diseases were summarized, which provided a new idea for the treatment of osteoarthritis.@*RESULTS@#OPA1 is a key factor involved in mitochondrial dynamics and energetics and in maintaining the stability of the mitochondrial genome. Accumulating evidence indicates that OPA1-mediated mitochondrial dynamics plays an important role in the regulation of skeletal system diseases such as osteoarthritis, osteoporosis, and osteosarcoma.@*CONCLUSION@#OPA1-mediated mitochondrial dynamics provides an important theoretical basis for the prevention and treatment of skeletal system diseases.
Subject(s)
Humans , GTP Phosphohydrolases/genetics , Mitochondrial Dynamics , Osteoarthritis , OsteoporosisABSTRACT
Objective: To investigate the clinicopathological characteristics and prognosis of high-grade B-cell lymphoma (HGBL) involving combined rearrangements of MYC, bcl-2 and bcl-6. Methods: A total of 1 138 cases of large B cell lymphoma (LBL) that were treated at the Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2017 to September 2020 were analyzed using fluorescence in situ hybridization (FISH) with probes against MYC, bcl-2 and bcl-6. The clinical and pathological data of the 45 patients with HGBL that had rearrangements of MYC and bcl-2 and/or bcl-6 were collected and retrospectively analyzed. Results: Among the 1 138 LBL, 45 (4.0%) cases had combined rearrangements of MYC, bcl-2 and/or bcl-6 that included 6 HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, 14 HGBL cases with MYC and bcl-2 rearrangements, and 25 HGBL cases with MYC and bcl-6 rearrangements. Of these 45 patients, 29 patients were male, and 16 patients were female, aged 29 to 83 years. HGBL with MYC, bcl-2 and bcl-6 rearrangements and HGBL with MYC and bcl-2 rearrangement were reclassified as the germinal center B-cell (GCB) subtype using the Hans algorithm. HGBL with MYC and bcl-6 rearrangement were reclassified as the GCB subtype (68.0%) and the non-GCB subtype (32.0%). The vast majority of HGBL cases had a high Ki-67 proliferation index. Most HGBL patients had advanced stage disease with a high IPI score and an increased LDH level. Also, some patients had clinical features including elevated plasma β2-microglobulin levels, B symptoms, and bone marrow involvement. The IPI scores and LDH levels were significantly different between the HGBL cases with MYC, bcl-2 and bcl-6 rearrangements and the HGBL cases with MYC and bcl-6 rearrangements (P<0.05). Compared with the HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, the HGBL cases with MYC and bcl-2 or bcl-6 rearrangements had a lower incidence of bone marrow involvement (P<0.05). There were no significant differences in the prognosis among HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, the cases with MYC and bcl-2 rearrangements, and the cases with MYC and bcl-6 rearrangements (P>0.05). Conclusions: HGBL with MYC, bcl-2 and/or bcl-6 rearrangements are rare types of B-cell lymphoma with high degree of malignancy and have a short overall survival. To reduce misdiagnosis and improve diagnostic accuracy, it is necessary to assess the patients' clinical features and conduct histopathological, immunohistochemical and FISH analyses.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , China , Gene Rearrangement , In Situ Hybridization, Fluorescence , Lymphoma, Large B-Cell, Diffuse/genetics , Prognosis , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-6/genetics , Proto-Oncogene Proteins c-myc/genetics , Retrospective StudiesABSTRACT
ObjectiveTo reveal the mechanism of action of Huangqi Guizhi Wuwutang in the treatment of rheumatoid arthritis by pharmacological research based on its clinical application. MethodThe collagen-induced arthritis (CIA) rat model was established by injecting bovine type Ⅱ collagen and Freund's adjuvant at the tail, and was treated with different concentrations of Huangqi Guizhi Wuwutang. The rats were randomly divided into blank group, model group, methotrexate (0.9 mg·kg-1) group, and Huangqi Guizhi Wuwutang low- and high-dose (5.13, 20.52 g·kg-1·d-1) groups, with continuous intragastric administration for 4 weeks. The degree of joint swelling, weight, degree of foot swelling and arthritis index score were determined and the pathological changes of ankle joints were detected by hematoxylin and eosin (HE) staining to observe the therapeutic effect of Huangqi Guizhi Wuwutang on rheumatoid arthritis. In addition, enzyme-linked immunosorbent assay (ELISA) and Western blot were used to measure the expression of interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 10 (IL-10) and tumor necrosis factor-α (TNF-α) in serum and the expression of nuclear factor kappa-B (NF-κB) pathway related proteins in synovial tissue, respectively to clarify the molecular mechanism of Huangqi Guizhi Wuwutang in the treatment of rheumatoid arthritis. ResultCompared with the conditions in blank group, the body weight and IL-10 level were decreased (P<0.01), and the degree of foot swelling and arthritis index score, the levels of IL-1β, IL-6 and TNF-α, and the expression of NF-κB pathway related proteins were increased (P<0.01,) in the model group, with impaired morphology and function of the ankle joint. Additionally, compared with the model group, Huangqi Guizhi Wuwutang low- and high-dose groups had increased body weight of rats and IL-10 level (P<0.01), and reduced degree of foot swelling and arthritis index score (P<0.05, P<0.01), levels of IL-1β, IL-6 and TNF-α (P<0.01) and expression of NF-κB pathway related proteins (P<0.05, P<0.01), with improved function and morphology of the ankle joint. ConclusionHuangqi Guizhi Wuwutang can significantly alleviate joint inflammatory injury by down-regulating NF-κB pathway and reducing the inflammatory response in CIA rats.
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Objective:To provide a reference for the choice of electronic data capture system used in clinical research, the function and performance of some tool software were expounded and compared.Methods:We selected three freely available systems of REDCap, Commcare, and OpenEDC as research objects, describing and comparing their user license acquisition path, data capture related functions, and information security assurance measures. This article reflected how the three kinds of tool software ensure research data privacy and scientificity, and presented the consideration of system security and accessibility.Results:REDCap was the most mature system of the three, which had a fairly comprehensive design in functional integrity, data security, user friendliness, and system scalability. Commcare system featured in the mobile collection, and supported the most abundant types of collected data, while OpenEDC was characteristic of low threshold and flexible deployment.Conclusions:REDCap system is widely applicable to small and medium scale medical research, including clinical trials, retrospective studies, cohort studies, and translational research. Commcare system is the preferred option for medical investigations represented by epidemiologic surveys, while OpenEDC is particularly suitable for investigator initiated studies.
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Objective:Small cell lung cancer (SCLC) is a highly malignant tumor with a high risk of brain metastasis (BMs). The purpose of this study was to evaluate the clinical factors affecting the occurrence of BMs in patients with stage IIB-IIIB SCLC who achieved complete remission (CR) after thoracic radio-chemotherapy.Methods:Clinical data of 191 patients with stage IIB-IIIB SCLC who achieved CR after thoracic radio-chemotherapy in Zhejiang Cancer Hospital from January 2009 to April 2016 were retrospectively analyzed. Common clinical factors related to the risk of BMs, including gender, age, thoracic radiotherapy dose, combined mode of radiotherapy and chemotherapy, pretreatment serum NSE and LDH, whether PCI was performed, TMN stage and PS score, were analyzed using log-rank method for univariate analysis, COX regression method for multivariate analysis and Kaplan-Meier method to plot the survival curve.Results:Univariate analysis showed that pretreatment LDH level≥240IU, pretreatment NSE ≥17 ng/ml and no PCI were positively correlated with the risk of BMs (all P<0.05). Multivariate analysis showed that the risk of BMs was only positively correlated with pretreatment LDH≥240IU [HR: 1.90, 95%CI(1.07-3.37), P=0.029], and no PCI [HR:2.08, 95%CI(1.17-3.72), P=0.013]. Conclusion:Pretreatment serum LDH levels provide important value for predicting the risk of BMs in patients with stage IIB-IIIB SCLC who achieve CR after thoracic radio-chemotherapy.
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Biopharmaceuticals are formulated using a variety of excipients to maintain their storage stability.However,some excipients are prone to degradation during repeated use and/or improper storage,and the impurities generated by their degradation are easily overlooked by end users and are usually not strictly monitored,affecting the stability of biopharmaceuticals.In this study,we evaluated the degra-dation profile of polyol excipient glycerol during repeated use and improper storage and identified an unprecedented cyclic ketal impurity using gas chromatography with mass spectrometry(GC-MS).The other polyol excipient,mannitol,was much more stable than glycerol.The effects of degraded glycerol and mannitol on the stability of the model biopharmaceutical pentapeptide,thymopentin,were also evaluated.The thymopentin content was only 66.4%in the thymopentin formulations with degraded glycerol,compared to 95.8%in other formulations after the stress test.Most glycerol impurities(i.e.,aldehydes and ketones)reacted with thymopentin,affecting the stability of thymopentin formulations.In conclusion,this work suggests that more attention should be paid to the quality changes of excipients during repeated use and storage.Additional testing of excipient stability under real or accelerated conditions by manufacturers would help avoid unexpected and painful results.
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A new phloroglucinol was isolated from 50% ethanol extract of Dryopteris fragrans by silica gel column chromatography, Sephadex LH-20 gel column chromatography, thin-layer chromatography(TLC), and preparative liquid column chromatography. On the basis of MS, ~1H-NMR, ~(13)C-NMR, and reference materials, compound 1 was identified as 2,5-cyclohexadien-1-one, 2-{[2,6-dihydroxy-4-methoxy-3-methyl-5-(1-isobutyl)phenyl]methyl}-3,5-dihydroxy-4,4-dimethyl-6-(1-oxobutyl)(1), and named disaspidin BB. Compound 1 was evaluated for its antibacterial activity. The experimental results showed that compared with the commonly used topical antibiotics erythromycin or mupirocin, disaspidin BB exhibited significant antibacterial activities against Staphylococcus epidermidis(SEP), S. haemolyticus(SHA), and methicillin-resistant S. aureus(MRSA)(P<0.05). Additionally, disaspidin BB was sensitive to ceftazidime-resistant SEP1-SEP4, SHA5-SHA7, MRSA8, and MRSA9. The MIC values of disaspidin BB against SEP and SHA were 1.67-2.71 μg·mL~(-1) and 10.00-33.33 μg·mL~(-1) respectively. Disaspidin BB has good antibacterial activities and deserves development as a new anti-infective drug for external use.
Subject(s)
Anti-Bacterial Agents/pharmacology , Dryopteris , Methicillin-Resistant Staphylococcus aureus , Microbial Sensitivity Tests , Phloroglucinol/pharmacology , Plant Extracts/pharmacologyABSTRACT
OBJECTIVE@#To explore the prescription patterns of different dosage forms of Chinese herbal medicines (CHMs) for the treatment of rheumatoid arthritis (RA) and their effects on immune-inflammatory indices.@*METHODS@#Clinical data were collected from patients with RA in 4 hospitals (3 Class A comprehensive hospitals and 1 Class B comprehensive hospital) in Anhui Province, China, from August 2012 to June 2018 via the electronic medical record gathering system. Following extraction of prescription information, each prescribed herb was quantified and standardized according to the knowledge base to establish a database of RA treatment formulae. The medical records were divided into the granules group and decoction pieces group. Core herbs and their combination patterns were obtained from the two groups of cases using Liquorice software. Changes in immune-inflammatory and hepatic and renal function indices were compared between the two groups using SPSS 23.0 software. The Aprior module of SPSS Clementine 11.1 software was applied to analyse the correlation between CHMs and improvement in indices. Finally, the ORACLE 10 g tool was used to evaluate the random walk model of the immune-inflammatory indices between the two groups.@*RESULTS@#(1) We retrospectively analysed 35,898 prescriptions for 6,829 patients with RA who received CHM treatment. There were 3,816 patients in the granules group and 3,013 in the decoction pieces group. (2) The core herbs were Pi (Spleen)-strengthening and dampness-resolving drugs, blood-activating and stasis-resolving drugs, wind/dampness-dispelling drugs and heat-clearing and detoxifying drugs. (3) Both dosage forms could improve immune-inflammatory indices in RA patients, with similar efficacy and no influence on hepatic or renal function. (4) Herba Siegesbeckiae and Oldenlandia had a stronger association with immune-inflammatory indices in the two groups. (5) The immune-inflammatory indices showed obvious improvement after treatment with granules and decoction pieces of CHMs, and there were long range correlations between the comprehensive evaluation indices and interventions.@*CONCLUSIONS@#The principal CHM treatment methods for RA in four hospitals in Anhui Province are strengthening Pi and resolving dampness, activating blood and resolving stasis, dispelling wind/dampness and clearing heat. Granules and decoction pieces of CHMs have similar efficacy in improving immune-inflammatory indices in RA patients and could be used as treatment options for RA.
Subject(s)
Humans , Arthritis, Rheumatoid/drug therapy , Data Mining , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional , Prescriptions , Retrospective StudiesABSTRACT
BACKGROUND@#Physical therapy is regarded as an essential aspect in achieving optimal outcomes following total knee arthroplasty (TKA). The coronavirus disease 2019 (COVID-19) pandemic has made face-to-face rehabilitation inaccessible. Virtual reality (VR) is increasingly regarded as a potentially effective option for offering health care interventions. This systematic review and meta-analysis investigate VR-based rehabilitation's effectiveness on outcomes following TKA.@*METHODS@#From inception to May 22, 2021, PubMed/Medline, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, Scopus, PsycINFO, Physiotherapy Evidence Database, China National Knowledge Infrastructure, and Wanfang were comprehensively searched to identify randomized controlled trials (RCTs) evaluating the effect of VR-based rehabilitation on patients following TKA according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and the Cochrane Handbook for Systematic Reviews of Interventions.@*RESULTS@#Eight studies were included in the systematic review, and seven studies were included in the meta-analysis. VR-based rehabilitation significantly improved visual analog scale (VAS) scores within 1 month (standardized mean difference [SMD]: -0.44; 95% confidence interval [CI]: -0.79 to -0.08, P = 0.02), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) within 1 month (SMD: -0.71; 95% CI: -1.03 to -0.40, P < 0.01), and the Hospital for Special Surgery Knee Score (HSS) within 1 month and between 2 months and 3 months (MD: 7.62; 95% CI: 5.77 to 9.47, P < 0.01; MD: 10.15; 95% CI: 8.03 to 12.27, P < 0.01; respectively) following TKA compared to conventional rehabilitation. No significant difference was found in terms of the Timed Up and Go (TUG) test.@*CONCLUSIONS@#VR-based rehabilitation improved pain and function but not postural control following TKA compared to conventional rehabilitation. More high-quality RCTs are needed to prove the advantage of VR-based rehabilitation. As the COVID-19 pandemic continues, it is necessary to promote this rehabilitation model.
Subject(s)
Humans , Arthroplasty, Replacement, Knee , COVID-19 , Randomized Controlled Trials as Topic , SARS-CoV-2 , Virtual RealityABSTRACT
@#N-methyl-D-aspartate receptor (NMDAR) antibody encephalitis is recognized as an autoimmune encephalitis, which is due to autoantibodies against synaptic NMDAR. This disorder affects individuals aged 23 months to 76 years and has a wide range of presentations. In Malaysia, more than 20 cases have been reported. Timely diagnosis and definitive immunotherapy are vital in optimizing functional recovery and prognosis. However, early diagnosis of the condition is often missed due to low awareness among clinicians in Malaysia. This article gathered the medical literature from Malaysia and highlights the aetio-pathophysiology, clinical presentation and management of the disease.