Effects of asparaginase-associated pancreatitis in children with haematological tumours.

Background: Asparaginase-associated pancreatitis (AAP) is a major challenge for continuing asparaginase therapy. We aimed to investigate the acute and long-term complications and survival rates related to first and second AAP episodes in Chinese children with haematological malignancies. Methods: We retrospectively analysed clinical data of children with pancreatitis who received asparaginase chemotherapy for acute lymphoblastic leukaemia (ALL), acute mixed cell leukaemia, and non-Hodgkin's lymphoma at Shanghai Children's Medical Center from November 2013 to November 2023. Results: Of the 76 children included in the study, 12 had local complications (15.79%), with no deaths recorded. Systemic complications manifested in 28 patients (36.84%), resulting in 3 deaths (3.95%). Four patients (5.26%) developed long-term complications (chronic pancreatitis or insulin-dependent diabetes mellitus). No significant differences in local or long-term complications were recorded between children in the asparaginase re-exposed (n=39) and non-re-exposed (n=45) groups. Among the re-exposed patients, eight (25.81%) experienced a second attack without fatalities or complications. Survival analysis of intermediate- to high-risk patients revealed a significantly higher event-free survival (EFS) rate for the re-exposed group than for the non-re-exposed group. The second AAP episode's occurrence and severity had no relation to the first AAP episode's severity, and the second AAP episode was significantly less severe than the first (p<0.001). Conclusions: The second AAP episode's occurrence is unrelated to the first AAP episode's severity, and the second AAP episode's severity is significantly lower than that of the first. Further, asparaginase therapy could improve EFS in children with intermediate and high-risk ALL.

Demographic and clinical characteristics associated with failure of physical therapy in chronic low back pain: a secondary analysis from a randomized controlled trial.

BACKGROUND: The effect of physical therapy on pain and disability alleviation in patients with chronic low back pain (cLBP) has been demonstrated, but the risk factors for treatment failure remain unknown. AIM: To explore the associations of baseline demographic and clinical characteristics with treatment failure after physical therapy intervention for cLBP. DESIGN: A secondary analysis of a single-blind randomized clinical trial. SETTING: A rehabilitation hospital. POPULATION: A total of 98 patients with cLBP completed the 12-month measurement. METHODS: Patients were randomly grouped into 3-month therapeutic aquatic exercise or physical therapy modalities. The primary outcome was treatment failure, which was defined as a decrease in the numeric rating scale to less than 2.0 points at 12-month follow-up. Associations between baseline demographic and clinical characteristics with risk of treatment failure were assessed by logistic regressions. RESULTS: The pain intensity in the failure cases was alleviated after 3-month intervention but continuously increased at 6- and 12-month follow-up (P<0.05). Old age was significantly associated with an increased risk of treatment failure (adjusted OR 3.26, 95% CI 1.11-9.60). Compared with those receiving physical therapy modalities, the patients receiving therapeutic aquatic exercise had less risk of treatment failure (adjusted OR 0.19, 95% CI 0.08-0.47), and age (P=0.022) was a modifier for this association. CONCLUSIONS: Compared with younger ones, older patients with cLBP had a higher risk of treatment failure after physical therapy and gained a stronger benefit of long-term pain alleviation from therapeutic aquatic exercise. CLINICAL REHABILITATION IMPACT: Therapeutic aquatic exercise is an effective therapy for cLBP and more helpful for preventing treatment failure than physical therapy modalities, especially for older patients.

Efficacy of Therapeutic Aquatic Exercise vs Physical Therapy Modalities for Patients With Chronic Low Back Pain: A Randomized Clinical Trial.

Importance: Therapeutic aquatic exercise is frequently offered to patients with chronic low back pain, but its long-term benefits are unclear. Objective: To assess the long-term effects of therapeutic aquatic exercise on people with chronic low back pain. Design, Setting, and Participants: This 3-month, single-blind randomized clinical trial with a 12-month follow-up period was performed from September 10, 2018, to March 12, 2019, and the trial follow-up was completed March 17, 2020. A total of 113 people with chronic low back pain were included in the experiment. Interventions: Participants were randomized to either the therapeutic aquatic exercise or the physical therapy modalities group. The therapeutic aquatic exercise group received aquatic exercise, whereas the physical therapy modalities group received transcutaneous electrical nerve stimulation and infrared ray thermal therapy. Both interventions were performed for 60 minutes twice a week for 3 months. Main Outcomes and Measures: The primary outcome was disability level, which was measured using the Roland-Morris Disability Questionnaire; scores range from 0 to 24, with higher scores indicating more severe disability. Secondary outcomes included pain intensity, quality of life, sleep quality, recommendation of intervention, and minimal clinically important difference. Intention-to-treat and per-protocol analyses were performed. Results: Of the 113 participants, 59 were women (52.2%) (mean [SD] age, 31.0 [11.5] years). Participants were randomly allocated into the therapeutic aquatic exercise group (n = 56) or the physical therapy modalities group (n = 57), and 98 patients (86.7%) completed the 12-month follow-up. Compared with the physical therapy modalities group, the therapeutic aquatic exercise group showed greater alleviation of disability, with adjusted mean group differences of -1.77 (95% CI, -3.02 to -0.51; P = .006) after the 3-month intervention, -2.42 (95% CI, -4.13 to -0.70; P = .006) at the 6-month follow-up, and -3.61 (95% CI, -5.63 to -1.58; P = .001) at the 12-month follow-up (P < .001 for overall group × time interaction). At the 12-month follow-up point, improvements were significantly greater in the therapeutic aquatic exercise group vs the physical therapy modalities group in the number of participants who met the minimal clinically important difference in pain (at least a 2-point improvement on the numeric rating scale) (most severe pain, 30 [53.57%] vs 12 [21.05%]; average pain, 14 [25%] vs 11 [19.30%]; and current pain, 22 [39.29%] vs 10 [17.54%]) and disability (at least a 5-point improvement on the Roland-Morris Disability Questionnaire) (26 [46.43%] vs 4 [7.02%]). One of the 56 participants (1.8%) in the therapeutic aquatic exercise group vs 2 of the 57 participants (3.5%) in the physical therapy modalities group experienced low back pain and other pains related to the intervention. Conclusions and Relevance: The therapeutic aquatic exercise program led to greater alleviation in patients with chronic low back pain than physical therapy modalities and had a long-term effect up to 12 months. This finding may prompt clinicians to recommend therapeutic aquatic exercise to patients with chronic low back pain as part of treatment to improve their health through active exercise rather than relying on passive relaxation. Trial Registration: Chinese Clinical Trial Registry: ChiCTR1800016396.

Single institute experience of intraoperative radiation therapy in early-stage breast cancer.

ABSTRACT: Intraoperative radiation therapy (IORT) is an alternative to whole breast irradiation in selected early-stage breast cancer patients. In this single institute analysis, we report the preliminary results of IORT given by Axxent Electronic Brachytherapy (eBT) system.Patients treated with lumpectomy and eBT within a minimum follow-up period of 12 months were analyzed. Eligible criteria include being over the age of 45, having unifocal invasive ductal carcinoma (IDC) or ductal carcinoma in situ <3 cm in diameter, not exhibiting lymph node involvement on preoperative images, and negative sentinel lymph node biopsy. The eBT was given by preloaded radiation plans to deliver a single fraction of 20 Gray (Gy) right after lumpectomy.From January 2016 to April 2019, a total of 103 patients were collected. There were 78 patients with IDC and 25 with ductal carcinoma in situ. At a mean follow-up time of 31.1 months (range, 14.5-54.0 months), the local control rate was 98.1%. Two IDC patients had tumor recurrences (1 local and 1 regional failure). Post-IORT radiotherapy was given to 4 patients. There were no cancer related deaths, no distant metastases, and treatment side effects greater than grade 3 documented.We report the largest single institute analysis using the eBT system in Taiwan. The low recurrence and complication rates at a 31.1 month follow-up time support the use of the eBT system in selected early-stage breast cancer patients.

Incidence and Risk Factors of Low Back Pain in Marathon Runners.

Purpose: The occurrence of low back pain (LBP) in marathon runners has been poorly understood. This study aimed to describe the risk factors and identify whether these factors can cause LBP in these athletes. Methods: A self-developed questionnaire was randomly distributed to 850 runners of running a half or a full marathon. Participants responded with the questionnaire focusing on previous training and running conditions after their competitions. Results: On the basis of the remaining 800 valid questionnaires, the incidence of LBP was 4.50% (n = 36). A total of 572 (71.5%) males and 228 (28.5%) females, with an average age range of 33.9 ± 9.0 years, came from different occupations with different physical activity characteristics. However, no significant associations between occupation and runners with LBP (p > 0.05) were found. In the final models, risk factors, including warm-up activities (p=0.012, OR = 2.617), fatigue (p = 0.008, OR = 2.680), running gait posture (p=0.041, OR = 2.273), and environmental temperature (p=0.020, OR = 6.584), were significantly associated with LBP in marathoners. Conclusion: Although LBP was uncommon in marathoners, it was linked to the factors such as insufficient warm-up activities, fatigue, poor running gait posture, and uncomfortable environmental temperature. Future studies need to validate these results. Nevertheless, these findings could still be useful for protecting the lower back area of runners clinically.

Association of Chronic Low Back Pain With Personal Space Regulation.

Background: While most previous studies regarding patients with chronic low back pain (CLBP) mainly focused on pain, disability, psychological damage, and intervention measures, the effect of CLBP on personal space remains unclear. The study aimed to assess the personal space of patients with CLBP and healthy controls, explored the differences between the two groups, and examined whether pain, dysfunction, anxiety, and depression affected the personal space regulation. Methods: The cross-sectional study recruited 24 patients with CLBP and 24 healthy controls at Shanghai Shangti Orthopedic Hospital and Shanghai University of Sport, Shanghai, China, from December 2018 to January 2019. A stop-distance paradigm was applied to measure the comfortable and uncomfortable distance under four conditions. A self-rating anxiety scale (SAS) and a self-rating depression scale (SDS) were used to examine the anxiety and depression levels of all participants. The pain intensity and dysfunction in the CLBP group were evaluated by the numeric rating scale and Roland-Morris questionnaire (RMDQ), respectively. Results: When approaching another individual or when being approached, the interpersonal distance under all the conditions in the CLBP group significantly differed from that in the healthy control group with larger space distances (p < 0.01). Gender had a significant main effect on the regulation of personal space in patients with CLBP (p < 0.05). The average pain intensity, scores on RMDQ, SAS, and SDS had a significant positive correlation with the interpersonal distance under the Same or Opposite Gender condition (p < 0.05). Conclusion: People with CLBP show an atypical personal space behavior and indeed have a greater interpersonal distance to strangers. The higher the pain intensity, dysfunction, anxiety, and depression, the greater the interpersonal distance in patients with CLBP. In the future, the effect and underlying neural mechanisms of pain and negative emotions on social withdrawal in patients should be examined.

The top 100 most-cited papers in long non-coding RNAs: a bibliometric study.

Up to 90% of the human genome is transcribed into Long-noncoding RNAs (lncRNAs) that longer than 200 nucleotides but do not code for proteins. LncRNAs play a vital role in a broad range of biological process, it's dysregulations and mutations are linked to the development and progression of various complex human diseases. Given the dramatic changes and growing scientific outputs in lncRNAs field, using a quantitative measurement to analyze and characterize the existing studies has become imperative.Bibliometric analysis is a widely used tool to assess the academic influence of a publication or a country in a specific field. However, a bibliometric analysis of the top 100 most-cited papers in lncRNAs area has not been conducted. Thus, we executed a bibliometric study to identify the authors, journals, countries and institutions that contributed most to the top 100 lncRNAs list, characterize the key words and focus of top 100 most-cited papers, and detect the factors related to their successful citation. This study provides a comprehensive list of the most influential papers on lncRNAs research and demonstrates the important advances in this field, which might be benefit to researchers in their paper publication and scientific cooperation.

Optimized production and safety evaluation of hispidin-enriched Sanghuangporus sanghuang mycelia.

Phellinus linteus, also known as the sanghuang mushroom, is a medicinal mushroom that has been recognized as beneficial to health for more thousands of years. Among its diverse valuable secondary metabolites, the yellow-brown styrylpyrone pigment hispidin has garnered significant attention due to its various pharmacological effects. However, recently after detailed morphological and molecular phylogenetic studies, the correct scientific name of the true sanghuang strains was shown not to be P. linteus but Sanghuangporus sanghuang. As the incorrect binomial name P. linteus has long been misleadingly referred, there is a need to evaluate the safety of S. sanghuang. Moreover, the growing conditions can impact the secondary metabolite profile of the fungi. Hence, this study is the first to optimize hispidin production and to investigate the genotoxic and oral toxic effects of hispidin-enriched S. sanghuang mycelia. In order to induce the biosynthesis of hispidin, 15 different culture media consisting of five carbon sources, five nitrogen sources, and five initial pH conditions were screened. Glucose and yeast extract at an initial pH of 5 were found to be the most suitable carbon and nitrogen sources, respectively, for the optimal growth and production of hispidin. Moreover, the production of hispidin was 3 mg/g in a 20-ton bioreactor under optimal conditions. Furthermore, the ames test, in vitro chromosome aberration test, acute oral toxicity test, and bone marrow micronucleus test were used to detect toxicological properties of 3 mg/g hispidin-enriched S. sanghuang mycelia. In all tests, there was no statistically significant difference between the mycelia and the negative control. Based on the results obtained, the present study demonstrates that 3 mg/g hispidin-enriched S. sanghuang mycelia has a very low order of toxicity, which supports its safety for human consumption.

Network and pathway-based analysis of microRNA role in neuropathic pain in rat models.

The molecular mechanisms underlying neuropathic pain (NP) remain poorly understood. Emerging evidence has suggested the role of microRNAs (miRNAs) in the initiation and development of NP, but the specific effects of miRNAs in NP are largely unknown. Here, we use network- and pathway-based methods to investigate NP-induced miRNA changes and their biological functions by conducting a systematic search through multiple electronic databases. Thirty-seven articles meet the inclusion criteria. Venn analysis and target gene forecasting are performed and the results indicate that 167 overlapping target genes are co-regulated by five down-regulated miRNAs (rno-miR-183, rno-miR-96, rno-miR-30b, rno-miR-150 and rno-miR-206). Protein-protein interaction network analysis shows that 77 genes exhibit interactions, with cyclic adenosine monophosphate (cAMP)-dependent protein kinase catalytic subunit beta (degree = 11) and cAMP-response element binding protein 1 (degree = 10) having the highest connectivity degree. Gene ontology analysis shows that these target genes are enriched in neuron part, neuron projection, somatodendritic compartment and nervous system development. Moreover, analysis of Kyoto Encyclopedia of Genes and Genomes reveals that three pathways, namely, axon guidance, circadian entrainment and insulin secretion, are significantly enriched. In addition, rno-miR-183, rno-miR-96, rno-miR-30b, rno-miR-150 and rno-miR-206 are consistently down-regulated in the NP models, thus constituting the potential biomarkers of this disease. Characterizing these miRNAs and their target genes paves way for their future use in clinical practice.

A Bioinformatic Analysis of MicroRNAs' Role in Human Intervertebral Disc Degeneration.

Objectives The aim of our study was to ascertain the underlying role of microRNAs (miRNAs) in human intervertebral disc degeneration (IDD). Design Bioinformatic analysis from multiple databases. Methods Studies of the association of miRNAs and IDD were identified in multiple electronic databases. All potential studies were assessed by the same inclusion and exclusion criteria. We recorded whether miRNA expression was commonly increased or suppressed in the intervertebral disc tissues and cells of IDD subjects. We used String to identify biological process and cellular component pathways of differentially expressed genes. Results We included fifty-seven articles from 1,277 records in this study. This report identified 40 different dysregulated miRNAs in 53 studies, including studies examining cell apoptosis (26 studies, 49.06%), cell proliferation (15 studies, 28.3%), extracellular matrix (ECM) degradation (10 studies, 18.86%), and inflammation (five studies, 9.43%) in IDD patients. Three upregulated miRNAs (miR-19b, miR-32, miR-130b) and three downregulated miRNAs (miR-31, miR-124a, miR-127-5p) were considered common miRNAs in IDD tissues. The top three biological process pathways for upregulated miRNAs were positive regulation of biological process, nervous system development, and negative regulation of biological process, and the top three biological process pathways for downregulated miRNAs were negative regulation of gene expression, intracellular signal transduction, and negative regulation of biological process. Conclusions This study revealed that miRNAs could be novel targets for preventing IDD and treating patients with IDD by regulating their target genes. These results provide valuable information for medical professionals, IDD patients, and health care policy makers.

Effect of 12-Week Whole-Body Vibration Exercise on Lumbopelvic Proprioception and Pain Control in Young Adults with Nonspecific Low Back Pain.

BACKGROUND Nonspecific low back pain (NSLBP) accounts for a large proportion of low back pain cases. The present study aimed to investigate the effect of the whole-body vibration (WBV) exercise on lumbar proprioception in NSLBP patients. It was hypothesized that WBV exercise enhances lumbar proprioception. MATERIAL AND METHODS Forty-two patients with NSLBP performed an exercise program 3 times a week for a total of 12 weeks of WBV. The lumbar proprioception was measured by joint position sense. Outcomes were lumbar angle deviation and visual analogue scale (VAS) score. RESULTS After the 12-week WBV exercise, lumbar flexion angle deviation was reduced from 3.65±2.26° to 1.90±1.07° (P=0.0001), and extension angle deviation was reduced from 3.06±1.85° to 1.61±0.75° (P=0.0001), significantly lower than baseline. After participating in the 12-week WBV exercise, a significant pain reduction was observed (P=0.0001). Men in the whole group (n=32) indicated significantly lower angle deviations in flexion and extension, whereas women (n=10) indicated significantly lower flexion angle deviation (P=0.037), and no significant difference was found in extension angle deviation (P=0.052). However, by subdividing the entire group (n=42) into poor and good proprioceptive groups, WBV exercise presented significant enhancement of lumbar proprioceptive ability in the poor flexion proprioception subgroup, poor extension proprioception subgroup, and good extension proprioception subgroup (each P=0.0001), but not in the subgroup with good flexion proprioceptive ability (P=0.165). CONCLUSIONS Lumbar flexion and extension proprioception as measured by joint position sense was significantly enhanced and pain was significantly reduced after 12-week WBV exercise in NSLBP patients. However, the patients with good flexion proprioceptive ability had limited proprioceptive enhancement.

[Myocardial revascularization of patients with diffuse coronary artery disease].

OBJECTIVE: Off-pump coronary artery bypass grafting (off-pump CABG) after off-pump coronary endarterectomy (CE) for myocardial revascularization is a way to rescue the patients with diffuse coronary artery disease (CAD). This study retrospectively analyzed its clinical outcomes and experiences, and explored the safety and effectiveness. METHODS: From October 2003 to December 2008, 177 diffuse CAD patients with 229 vascular lesions received off-pump CABG plus CE. Incision was made at the hardest part of coronary artery and ≥ 2 cm from the distal intervention site. Then bypass graft was performed by internal mammary artery or saphenous vein. RESULTS: The intra-operative blood tests showed that 215 (93.9%) bridges were satisfied with (27 ± 12) ml/min blood flow while 14 bridges were dissatisfied. The blood flow was (7 ± 4) ml/min. Six (3.4%) cases suffered peri-operative myocardial infarction. Among them, 3 patients had no significant cardiac hemodynamic changes. Three suffered a low cardiac output and improved by intra-aortic balloon counter pulsation support. And they were then discharged after treatment. After 3 - 40 months, 98 patients underwent coronary angiography to measure the graft latency. And the blood flow was excellent. CONCLUSIONS: Off-pump CABG plus CE for diffuse coronary artery disease is both feasible and safe. And it is an effective treatment with a high degree of vascularization.

Preclinical safety evaluation of 18F-FHBG: a PET reporter probe for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk) or mutant HSV1-sr39tk's expression.

UNLABELLED: 9-(4-(18)F-Fluoro-3-[hydroxymethyl]butyl)guanine ((18)F-FHBG) is a sensitive and specific PET reporter probe for imaging the PET reporter genes, herpes simplex 1 thymidine kinase (HSV1-tk) and its mutant HSV1-sr39tk. (18)F-FHBG has suitable pharmacokinetics and dosimetry for clinical applications and imaging of HSV1-TK has been demonstrated in the livers of hepatocellular cancer patients. METHODS: Male and female Sprague-Dawley rats and New Zealand White rabbits were divided into equal groups receiving either 14 microg/kg cold FHBG or carrier solution, for a 14-d acute toxicity assessment. We monitored body weight, food and water consumption, body temperature, cardiovascular electrical and functional indices, respiratory performance and oxygen saturation, comprehensive blood chemistry, complete blood count (CBC), and urinalysis. We conducted daily cage-side examinations for the detection of any clinical abnormalities. Tissues of the animals that were euthanized and necropsied on day 14 were prepared for histopathologic examination. RESULTS: No significant differences in cardiovascular and respiratory parameters, food consumption, body weight, urine components, or clinical signs attributable to test article toxicity were observed between the treatment and control groups. Any differences noted in the blood chemistry and CBC parameters were deemed to be incidental findings unrelated to the administration of the FHBG. CONCLUSION: Acute toxicity evaluation of FHBG at 100 times the expected human dose does not indicate harm to organ function or tissues. The Food and Drug Administration has approved FHBG as an Investigational New Drug.

[Off-pump coronary artery bypass grafting with only bilateral internal mammary artery composite Lima-Rima Y graft].

OBJECTIVE: To improve the early and late benefits (the patency and total myocardium revascularization) of coronary artery bypass grafting, stimulate us using only bilateral internal mammary artery (BIMA) composite Lima (left internal mammary artery)-Rima (right internal mammary artery) Y graft with off-pump, here is the early evaluation. METHODS: From October 2002 to December 2005, 125 patients underwent off-pump coronary artery bypass grafting with the only composite grafts. The bilateral semi-skeletonization internal mammary artery pedicles composed the Y graft, the free Rima was anastomosed to the in situ Lima. The operation was performed off-pump and sequential anastomosis. RESULTS: Four hundred and thirteen grafts for 125 patients, average number of grafts per patient was 3.3. Graft flow was measured with Transit time flowmeter during operation time. All grafts were patent during operation. There was no death perioperative period. CONCLUSION: Off-pump coronary artery bypass grafting with only bilateral internal mammary artery composite Lima-Rima Y graft is secure and feasible. The technique could achieve total arterial myocardium revascularization and avoiding any procedure on the ascending aorta.

Repair of left ventricular aneurysm during off-pump coronary artery bypass surgery.

BACKGROUND: Acute myocardial infarction can result in left ventricular aneurysm, which may in turn cause congestive heart failure, ventricular arrhythmia and thromboembolic events. This study evaluates results achieved with a modified linear closure of left ventricular aneurysms during off-pump coronary artery bypass surgery. METHODS: From January 2001 to May 2004, 75 patients were operated on for nonruptured, postinfarctional, left ventricular aneurysm during off-pump coronary artery bypass surgery. Repair was completed on the beating heart to minimize ischaemia and allow assessment of wall function and viability to guide closure. All patients presented with symptoms of angina and congestive heart failure or ventricular arrhythmia. The majority (75%) of the patients were in NYHA functional class III or IV. Preoperative ejection fraction was 26% +/- 9%. The mean left ventricular, end diastolic diameter was (57.5 +/- 7.1) mm. The ventricular preoperative and postoperative performances were compared. chi2 test and Student's t test were used to analyse the outcomes. A P value less than 0.05 was considered significant. RESULTS: Hospital mortality was 1.3% (1/75). Coronary artery bypass was performed with an average of (3.3 +/- 1.2) grafts per patient. At the time of followup, all the patients had no symptoms. The mean NYHA class and ejection fraction increased significantly (P < 0.001). The mean left ventricular, end diastolic diameter decreased significantly (P < 0.001). CONCLUSIONS: Surgical closure of left ventricular aneurysm can be performed during off-pump coronary artery bypass. The operation is associated with a low inhospital mortality and morbidity. A postoperative improvement in the early term cardiac functions and symptoms and quality of life was documented, increasing our expectations of an increased long-term survival.