Cytotoxic xanthanolide sesquiterpenes from the fruits of Xanthium italicum Moretti.

One previously undescribed xanthanolide sesquiterpene dimer pungiolide P (1), possessing an unprecedented scaffold with a 5/7/5/7/5 ring system skeleton and its intermediate pungiolide Q (2), ten xanthanolide sesquiterpenes (3-12), two eudesmene sesquiterpene derivatives (13-14), one phenylpropionic acid derivative (15), together with eleven known compounds (16-26) were obtained from the fruits of Xanthium italicum Moretti. A possible biosynthetic pathway for pungiolide P (1) was also proposed, which was supported by its bio-synthetic intermediate (2). Compounds 1, 4-5, 18-21, and 25 exhibited cytotoxic activity against a variety of human cancer cell lines. Furthermore, compounds 1, 4-5, could cause blockage of the cell cycle in the G2/M phase and induce apoptosis in H460 cells. Notably, pungiolide P (1) exhibited significantly superior cytotoxicity compared to previously reported compounds, providing valuable insights for natural anti-tumor sources.

Minor Hydroxylated Triterpenoids Produced in Engineered Yeast by the Enzymes OSC and CYP716s from the Plant Enkianthus chinensis and Their Anti-Inflammatory and Hepatoprotective Activities.

Triterpenoids are a type of specialized metabolites that exhibit a wide range of biological activities. However, the availability of some minor triterpenoids in nature is limited, which has hindered our understanding of their pharmacological potential. To overcome this limitation, heterologous biosynthesis of triterpenoids in yeast has emerged as a promising and time-efficient production platform for obtaining these minor compounds. In this study, we analyzed the transcriptomic data of Enkianthus chinensis to identify one oxidosqualene cyclase (EcOSC) gene and four CYP716s. Through heterologous expression of these genes in yeast, nine natural pentacyclic triterpenoids, including three skeleton products (1-3) produced by one multifunctional OSC and six minor oxidation products (4-9) catalyzed by CYP716s, were obtained. Of note, we discovered that CYP716E60 could oxidize ursane-type and oleanane-type triterpenoids to produce 6ß-OH derivatives, marking the first confirmed C-6ß hydroxylation in an ursuane-type triterpenoid. Compound 9 showed moderate inhibitory activity against NO production and dose-dependently reduced IL-1ß and IL-6 production at the transcriptional and protein levels. Compounds 1, 2, 8, and 9 exhibited moderate hepatoprotective activity with the survival rates of HepG2 cells from 61% to 68% at 10 µM.

Diverse prenylated C6-C3 derivatives from the stems and branches of Illicium ternstroemioides A. C. Smith with anti-inflammatory and antiviral activities.

Fifteen unreported prenylated C6-C3 derivatives (1-15) were isolated from the stems and branches of Illicium ternstroemioides A. C. Smith, including one bis-prenylated C6-C3 derivative (1), three prenylated C6-C3 derivative-shikimic acid ester hybrids (2-4) and 11 prenylated C6-C3 monomers (5-15). The structures of compounds 1-15 were elucidated by spectroscopic analysis (UV, IR, 1D and 2D NMR, and HRESIMS). The absolute configurations of the compounds were determined using electronic circular dichroism (ECD), induced circular dichroism (ICD), and the modified Mosher's method. Among the isolates, compounds 11, 12, and 15 exhibited significant anti-inflammatory activities by inhibiting the nitric oxide with IC50 values ranging from 1.89 to 24.83 µM in lipopolysaccharide-stimulated murine RAW 264.7 macrophages and murine BV2 microglial cells; compounds 2, 3, and 7 exhibited antiviral activitives against Coxsackievirus B3 with an IC50 value of 33.3, 25.9, and 27.8 µM, respectively.

Minor terpenoids from the leaves of Craibiodendron yunnanense.

One new taraxastane-type triterpenoid, three new grayanane-type diterpenoids (2 - 4), and 12 known compounds (5 - 16) were isolated from the leaves of Craiobiodendron yunnanens W. W. Smith. The structures of these compounds were elucidated on the basis of their spectroscopic data and chemical evidence. Compounds 1 and 8 exhibited partly anti-inflammatory activity based on the inhibition of NF-κB activity in SW480 cells at 10 µM with inhibition ratios of 60.53 and 59.20%, respectively. Compounds 10 and 13 showed excellent cytotoxicity against human leukemia cell (MV4-11) at 10 µM with inhibition ratios of 43.02 and 49.11%, respectively.

CT Scans and Cancer Risks: A Systematic Review and Dose-response Meta-analysis.

BACKGROUND: There is still uncertainty on whether ionizing radiation from CT scans can increase the risks of cancer. This study aimed to identify the association of cumulative ionizing radiation from CT scans with pertaining cancer risks in adults. METHODS: Five databases were searched from their inception to November 15, 2020. Observational studies reporting cancer risks from CT scans in adults were included. The main outcome included quantified cancer risks as cancer case numbers in exposed/unexposed adult participants with unified converted measures to odds ratio (OR) for relative risk, hazard ratio. Global background radiation (2.4 mSv per year) was used as control for lifetime attribution risk (LAR), with the same period from incubation after exposure until survival to 100 years. RESULTS: 25 studies were included with a sum of 111,649,943 participants (mean age: 45.37 years, 83.4% women), comprising 2,049,943 actual participants from 6 studies with an average follow-up period as 30.1 years (range, 5 to 80 years); 109,600,000 participants from 19 studies using LAR. The cancer risks for adults following CT scans were inordinately increased (LAR adults, OR, 10.00 [95% CI, 5.87 to 17.05]; actual adults, OR, 1.17 [95%CI, 0.89 to 1.55]; combined, OR, 5.89 [95%CI, 3.46 to 10.35]). Moreover, cancer risks elevated with increase of radiation dose (OR, 33.31 [95% CI, 21.33 to 52.02]), and multiple CT scan sites (OR, 14.08 [95% CI, 6.60 to 30.05]). The risk of solid malignancy was higher than leukemia. Notably, there were no significant differences for age, gender, country, continent, study quality and studying time phrases. CONCLUSIONS: Based on 111.6 million adult participants from 3 continents (Asia, Europe and America), this meta-analysis identifies an inordinately increase in cancer risks from CT scans for adults. Moreover, the cancer risks were positively correlated with radiation dose and CT sites. The meta-analysis highlights the awareness of potential cancer risks of CT scans as well as more reasonable methodology to quantify cancer risks in terms of life expectancy as 100 years for LAR. PROSPERO TRIAL REGISTRATION NUMBER: CRD42019133487.

Minor terpenoids from the stems and twigs of Rhododendron ovatum.

Four minor undescribed terpenoids, including a monoterpenoid (1) and three triterpenoids (3, 6 and 7), together with 26 known terpenoids were isolated from the stems and twigs of Rhododendron Ovatum. Their structures were identified by extensive spectroscopic analyses and electronic circular dichroism (ECD) techniques. Compound 10 showed excellent cytotoxicity against human colon cancer cell (HCT-116) with IC50 value of 2.56 µM. Compounds 9 and 19 exhibited partly inhibitory effects on nitric oxide production stimulated by lipopolysaccharide-induced neuroinflammation in microglia cells at 10 µM with inhibition ratios of 39.70% and 28.08%, respectively.

Decompression Using Minimally Invasive Surgery for Lumbar Spinal Stenosis Associated with Degenerative Spondylolisthesis: A Review.

Lumbar spinal stenosis (LSS), which often occurs concurrently with degenerative spondylolisthesis (DS), is a common disease in the elderly population, affecting the quality of life of aged people significantly. Notwithstanding the frequently good effect of conservative therapy on LSS, a minority of the patients ultimately require surgery. Surgery for LSS aims to decompress the narrowed spinal canals with preservation of spinal stability. Traditional open surgery, either pure decompression or decompression with fusion, was considered effective for the treatment of LSS with or without DS. However, the long-term clinical outcomes of traditional open surgery are still unclear. Moreover, the disadvantages of conventional open surgery are extensive, examples including tissue injuries or secondary instability, with limited outcomes and significant reoperation rates. With the development and improvement of surgical tools, various minimally invasive spine surgery (MISS) methods, including indirect decompression techniques of interspinous process devices (IPDs) and direct decompression techniques such as microscopic spine surgery or endoscopic spine surgery (ESS), have been updated with enhancement. IPDs, such as Superion devices, were reported to behave with comparable physical function, disability, and symptoms outcomes to laminectomy decompression. As an emerging technique of MISS, ESS has beneficial hallmarks including minimal tissue injuries, reduced complication rates, and shortened recovery periods, thus gaining popularity in recent years. ESS can be classified in terms of endoscopic hallmarks and approaches. Predictably, with the continuous development and gradual maturity, MISS is expected to replace traditional open surgery widely in the surgical treatment of LSS associated with DS in the future.

Comparison of two methods in the treatment of congenital pseudarthrosis of clavicle: multicenter experience.

BACKGROUND: Congenital pseudoarthrosis of the clavicle (CPC) is an uncommon entity. Owing to its scarce presentation, treatment of this disorder has not been well established. This study aimed (1) to compare surgical treatment methods that included excision of pseudoarthrosis and iliac crest bone graft and fixate with either the elastic stable intramedullary nail (ESIN) or K-wires or plate and screws, and (2) to assess the clinical outcomes of two different surgical methods. METHODS: A multi-central retrospective study was performed between 2013 and 2017 in four tertiary teaching hospitals. Fifteen clavicles of 11 children were identified as CPC. All patients underwent pseudarthrosis resection and iliac crest bone autograft. They were divided into two groups as per the surgical treatment they underwent-plate stabilization as group A and elastic stable intramedullary nailing (ESIN) or K-wires as group B. Nine clavicles in 6 patients in group A and 6 clavicles in 5 patients in group B, were included. The Quick Disabilities of the Arm and Shoulder (QuickDASH) score was used to assess patients' satisfaction and function following treatment at each follow-up. RESULTS: There were eight boys and three girls, with an average age of 4.7 years. All patients, except one with intellectual impairments, had radiological healing. Implant removal time was significantly shorter in group B compared to group A. No statistically significant differences existed in terms of age at surgery, time of radiological healing, complication, and clinical outcome between different groups. CONCLUSION: Surgical resection of pseudoarthrosis with an iliac crest bone graft was an effective means of surgical treatment in CPC. However, ESIN or K-wires can achieve shorter union time compared to the plate. Hence, surgical treatment is recommended for congenital pseudarthrosis of clavicular in pediatric patients. LEVEL OF EVIDENCE: Retrospective comparative study; Level III.

Oxygenated pentacyclic triterpenoids from the stems and branches of Enkianthus chinensis.

Thirty new pentacyclic triterpenoids, including five oleanane-type (1-5), twenty-three ursane-type (9-23, 26-33) and two taraxerane-type (24 and 25), along with fourteen known triterpenoids, were isolated from the stems and branches of Enkianthus chinensis. Their structures were elucidated by extensive spectroscopic analyses, X-ray crystallographic data and electronic circular dichroism (ECD) techniques. Sixteen compounds (1-5, 9-13, 20, 22, 32, 34-36) bearing a gem-hydroxymethyl group at C-4 represent rare examples of pentacyclic triterpenoids. In the in vitro biological activity evaluation, compounds 8, 9, 12-14, 17, 24, and 44 exhibited potent hepatoprotective effects at 10 µM. Moreover, compound 25 showed latent activity against HSV-1 with an IC50 value of 6.4 µM.

Balneotherapy for Fibromyalgia Syndrome: A Systematic Review and Meta-Analysis.

(1) Background: The efficiency of balneotherapy (BT) for fibromyalgia syndrome (FMS) remains elusive. (2) Methods: Cochrane Library, EMBASE, MEDLINE, PubMed, Clinicaltrials.gov, and PsycINFO were searched from inception to 31 May 2020. Randomized controlled trials (RCTs) with at least one indicator were included, i.e., pain, Fibromyalgia Impact Questionnaire (FIQ), Tender Points Count (TPC), and Beck's Depression Index (BDI). The outcome was reported as a standardized mean difference (SMD), 95% confidence intervals (CIs), and I2 for heterogeneity at three observational time points. GRADE was used to evaluate the strength of evidence. (3) Results: Amongst 884 citations, 11 RCTs were included (n = 672). Various BT regimens were reported (water types, duration, temperature, and ingredients). BT can benefit FMS with statistically significant improvement at different time points (pain of two weeks, three and six months: SMD = -0.92, -0.45, -0.70; 95% CI (-1.31 to -0.53, -0.73 to -0.16, -1.34 to -0.05); I2 = 54%, 51%, 87%; GRADE: very low, moderate, low; FIQ: SMD = -1.04, -0.64, -0.94; 95% CI (-1.51 to -0.57, -0.95 to -0.33, -1.55 to -0.34); I2 = 76%, 62%, 85%; GRADE: low, low, very low; TPC at two weeks and three months: SMD = -0.94, -0.47; 95% CI (-1.69 to -0.18, -0.71 to -0.22); I2 = 81%, 0; GRADE: very low, moderate; BDI at six months: SMD = -0.45; 95% CI (-0.73 to -0.17); I2 = 0; GRADE: moderate). There was no statistically significant effect for the TPC and BDI at the remaining time points (TPC at six months: SMD = -0.89; 95% CI (-1.85 to 0.07); I2 = 91%; GRADE: very low; BDI at two weeks and three months: SMD = -0.35, -0.23; 95% CI (-0.73 to 0.04, -0.64 to 0.17); I2 = 24%, 60%; GRADE: moderate, low). (4) Conclusions: Very low to moderate evidence indicates that BT can benefit FMS in pain and quality-of-life improvement, whereas tenderness and depression improvement varies at time phases. Established BT regimens with a large sample size and longer observation are needed.

Low Radiation X-rays: Benefiting People Globally by Reducing Cancer Risks.

Modern medical imaging facilitates the diagnosis and treatment of human diseases. However, few people are aware of the cons of radiation exposure from medical imaging. Emerging evidence reveals that cumulative doses of radiation exposure will increase the morbidity and mortality of pertaining cancer. As a special young population, patients with adolescent idiopathic scoliosis (AIS) suffer more radiation harms from repeated diagnostic imaging, most of which can be avoided in clinical practice. Accumulating evidence highlights reduced cancer risks of radiation exposure for AIS patients with low/zero radiation imaging modalities proposed, amongst which easy conversion from anterior-posterior (AP) to posterior-anterior (PA) projection for whole-spine radiographs should be stressed. It can greatly reduce radiation doses without compromising the quality of diagnostic imaging. Tight collimation combined with PA projection can further reduce radiation harms, and need to be spread to benefit people globally.

Cancer and mortality risks of patients with scoliosis from radiation exposure: a systematic review and meta-analysis.

PURPOSE: The study aimed for unraveling the long-term health impact of cumulative radiation exposure from full-spine radiographs on children/adolescents with scoliosis. METHODS: All cohort, case-control or cross-sectional studies about radiation exposure to scoliosis patients with follow-up period as 20 years or more were included. Meta-analyses were performed for outcomes reported in two or more studies. RESULTS: A total of 9 eligible studies involving 35,641 participants between 1912 and 1990 fulfilled the inclusion criteria, including 18,873 patients with scoliosis and 16,768 controls as regional matched general population. The average number of full-spine radiographs was 23.13 (range: 0-618) according to 14,512 patients between 1912 and 1990 in five studies. The estimated mean cumulated radiation dose of breast was 11.35 cGy. In comparison with controls, pooled incidence rates of cancer, breast cancer and cancer mortality of patients with scoliosis were statistically significant higher [rate of cancer, odds risk (OR) = 1.46, p < 0.00001; breast cancer, OR = 1.20, p = 0.02; cancer mortality, OR = 1.50, p < 0.00001]. No statistically significant differences were found in terms of reproductive events for scoliosis patients, pulmonary function and physical activity for adolescent idiopathic scoliosis patients. CONCLUSIONS: Based on 35,641 participants with over 20 years' observations from 1912 to 1990, repeated radiographs and pertaining cumulative radiation dose resulted in elevated rates of cancer, breast cancer and cancer mortality for children/adolescents with scoliosis in comparison with matched general population. It is recommended that low-radiation or radiation-free and efficient methods should be used to monitor the evolution of children/adolescents with scoliosis.

Locking plate versus external fixation in the treatment of displaced femoral supracondylar fracture in children.

BACKGROUND: Displaced supracondylar femoral fractures (SFF) are difficult injuries to treat in children. Several techniques have been widely used but few studies have compared the merits and drawbacks of each surgical intervention in order to analyze clinical values. The aim of this study was to (1) evaluate postoperative and functional conditions after treatments with locking plate (LP) or external fixation (EF), (2) observe adverse events associated with these two techniques, and (3) evaluate the clinical value of these two techniques. METHODS: Twenty-eight patients less than 14 years of age were included in this study with supracondylar femoral fractures. They underwent locking plate or external fixation in authors' hospital. The postoperative healing and functional outcome were elevated according to radiographic and clinical measures, including American Knee Society Score (KSS). Fisher's exact test and independent samples t test were used for statistical analysis. RESULTS: All fractures healed without delayed union. The KSS scoring results of locking plate and external fixation groups were both excellent. The alignment of lower limbs was acceptable with knee valgus less than 2° for all involved patients. In addition, leg length discrepancy was less than 1 cm. No acute or severe complications were noted. There was significant difference in union time (p = 0.03), operating time (p< 0.001), intraoperative blood loss (p< 0.001), and limb length discrepancy (p = 0.04) between LP group and EF group. CONCLUSIONS: External fixation is superior than locking plate in terms of union, operation time phrases, and intraoperative blood loss. EF techniques are better options for treating displaced supracondylar femoral fracture in children. LEVEL OF EVIDENCE: Retrospective comparative study; level III.

Preliminary evaluation and discussion of the safety of left innominate vein resection.

BACKGROUND: To evaluate the safety of resection of anterior mediastinal lesions involving the left innominate vein (LIV) and analyze the risk factors affecting LIV resection safety. METHODS: Patients who underwent anterior mediastinal lesion and LIV resection from January 2010 to December 2018 in the Department of Thoracic Surgery of Tangdu Hospital, Air Force Medical University, were followed up, and preoperative, intraoperative and postoperative factors were analyzed. RESULTS: Forty-eight patients who underwent anterior mediastinal lesion and LIV resection from January 2010 to December 2018, except for 2 who died of lung infection-induced respiratory failure, were followed up, with an average follow-up time of 32 months (range, 6-72 months). Postoperative: in 31 cases (67.39%), patients did not manifest LIV resection-associated complications; in 15 cases (32.61%), patients manifested mild LIV resection-associated complications; no patient manifested severe LIV resection-associated complications. The average operation time, average blood loss and average hospitalization time were 155.17 min, 324.13 mL and 11.83 days, respectively. Univariate analysis showed that the degree of LIV invasion and surgical approach were risk factors for predicting LIV resection safety. CONCLUSIONS: For anterior mediastinal lesions involving the LIV, LIV resection is a simple, safe and effective surgical procedure.

Local Infiltration Analgesia with Ropivacaine Improves Postoperative Pain Control in Ankle Fracture Patients: A Retrospective Cohort Study.

Purpose: The study aimed at investigating the effect of local infiltration analgesia (LIA) with ropivacaine on postoperative analgesia for patients undergoing ankle fracture surgery. Methods: Consecutive patients were retrospectively included and analysed according to their medical records from July 2014 to August 2018 in a tertiary hospital. Inclusion criteria were patients undergoing open reduction and internal fixation (ORIF) for ankle fractures under general anaesthesia. Moreover, patients should have received intravenous patient-controlled analgesia (iPCA) or LIA + iPCA for postoperative pain relief. The primary outcome indicator was visual analogue scale (VAS) from 8 hours to 48 hours after surgery. Secondary outcomes included postoperative opioid requirement, need for rescue medication, opioid-related adverse effects, and wound complications. Results: In total, 89 consecutive patients were included in the study. There were 48 males and 41 females. The average age was 44.6 ± 7.0 years, and VAS scores were significantly lower in the LIA + iPCA group at 8 hours after surgery (1.51 ± 0.58 cm vs 4.77 ± 1.83 cm, p < 0.001). The time to first tramadol consumption was longer (580 ± 60.9 minutes vs 281 ± 86.4 minutes, p < 0.001). The time to first tramadol consumption was longer (580 ± 60.9 minutes vs 281 ± 86.4 minutes, p < 0.001). The time to first tramadol consumption was longer (580 ± 60.9 minutes vs 281 ± 86.4 minutes, p < 0.001). The time to first tramadol consumption was longer (580 ± 60.9 minutes vs 281 ± 86.4 minutes, p < 0.001). The time to first tramadol consumption was longer (580 ± 60.9 minutes vs 281 ± 86.4 minutes. Conclusions: The retrospective cohort study indicates that LIA with ropivacaine can provide better early postoperative pain management with a reduction of VAS scores for ankle fracture surgery. Patients receiving wound infiltration also experience decreased opioid consumption, a lower rate of analgesia-related side effects, and comparable wound complication rate.

LncRNA MEG3 acts a biomarker and regulates cell functions by targeting ADAR1 in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most prevalent malignancy and has the fourth highest global cancer mortality rate. Early diagnosis and prompt medical attention can improve quality of life and the prognosis of CRC patients. Accumulating evidence reveals that long non-coding RNAs (lncRNAs) function as oncogenes or anti-oncogenes, as well as biomarkers in various cancers. AIM: To investigate the levels and molecular mechanism of the lncRNA maternally expressed gene 3 (MEG3) in CRC. METHODS: The levels of lncRNA MEG3 in CRC tissue, serum and cell line samples were explored via qRT-PCR. The relationship between MEG3 levels and clinicopathological features in CRC was investigated. The diagnostic and prognostic values of serum MEG3 levels were analyzed with ROC curves and Kaplan­Meier survival curves, respectively. RESULTS: Significant decreased levels of MEG3 existed in CRC tissue, cell lines and serum. CRC patients with down-regulated serum MEG3 levels had larger tumor sizes, and advanced clinical stages. The sensitivity and specificity of serum MEG3 levels in CRC detection was 0.667 and 0.875, respectively. Tumor size, T stages, and serum MEG3 levels are indie factors that produce an effect on CRC patients' prognosis. Kaplan­Meier survival curves suggested that CRC patients with high levels of MEG3 had a remarkably better overall survival rate. CONCLUSION: LncRNA MEG3 is down-regulated in CRC, and regulates cell functions by targeting adenosine deaminase's effect on RNA 1 in CRC.

Development and validation of a nomogram for osteosarcoma-specific survival: A population-based study.

This study aimed to establish a comprehensive prognostic system for osteosarcoma based on a large population database with high quality.The Surveillance, Epidemiology, and End Results (SEER) Program database was used to identify patients with osteosarcoma from 1973 to 2015. Multivariate analysis was performed to screen statistically significant variables. A nomogram was constructed by R software to predict the 3-, 5- and 10-year survival rates. Predictive abilities were compared by C-indexes, calibration plots, integrated discrimination improvement (IDI), net reclassification improvement (NRI), as well as decision curve analysis (DCA).In total, 4505 osteosarcoma patients were identified. They were divided into training (70%, n = 3153) and validating (30%, n = 1352) groups. Multivariate analyses identified independent predictors. Subsequently, the nomogram system of a new model was established, which comprised 7 variables as age, sex, site, decade of diagnosis (DOD), extent of disease (EOD), tumor size and patients undergoing tri-modality therapy (surgery, radiotherapy and chemotherapy). It provided better C-indexes than the model without therapies (0.727, 0.712 vs 0.705, 0.668) in the 2 cohort, respectively. As well, the new model had good performances in the calibration plots. Moreover, both IDI and NRI improved for 3-, 5- and 10-year follow-up of C-indexes. Finally, DCA demonstrated that the nomogram of new model was clinically meaningful.We developed a reliable nomogram for prognostic determinants and treatment outcome analysis of osteosarcoma, thus helping better choose medical examinations and optimize therapeutic regimen under the cooperation among oncologists and surgeons.