Machine learning-aided metallomic profiling in serum and urine of thyroid cancer patients and its environmental implications.

The incidence rate of thyroid cancer has been growing worldwide. Thyroid health is closely related with multiple trace metals, and the nutrients are essential in maintaining thyroid function while the contaminants can disturb thyroid morphology and homeostasis. In this study, we conducted metallomic analysis in thyroid cancer patients (n = 40) and control subjects (n = 40) recruited in Shenzhen, China with a high incidence of thyroid cancer. We found significant alterations in serumal and urinary metallomic profiling (including Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Sr, Cd, I, Ba, Tl, and Pb) and elemental correlative patterns between thyroid cancer patients and controls. Additionally, we also measured the serum Cu isotopic composition and found a multifaceted disturbance in Cu metabolism in thyroid disease patients. Based on the metallome variations, we built and assessed the thyroid cancer-predictive performance of seven machine learning algorithms. Among them, the Random Forest model performed the best with the accuracy of 1.000, 0.858, and 0.813 on the training, 5-fold cross-validation, and test set, respectively. The high performance of machine learning has demonstrated the great promise of metallomic analysis in the identification of thyroid cancer. Then, the Shapley Additive exPlanations approach was used to further interpret the variable contributions of the model and it showed that serum Pb contributed the most in the identification process. To the best of our knowledge, this is the first study that combines machine learning and metallome data for cancer identification, and it supports the indication of environmental heavy metal-related thyroid cancer etiology.

Multiple Protocols Combined with Hyperbaric Oxygen Therapy on the Maintenance of Ovarian Function in Patients After Ovarian Cystectomy.

Objective: This study aims to explore the effect of adjuvant hyperbaric oxygen therapy on ovarian function after laparoscopic ovarian cystectomy. Methods: A total of 60 patients with ovarian cysts treated at our hospital from January 2018 to August 2020 were enrolled. According to the different treatment modalities, the patients were divided into the control and observation groups. Patients in both groups underwent laparoscopic ovarian cystectomy with oral administration of Chinese patent medicine Kuntai capsules after surgery. Hyperbaric oxygen therapy was added to patients in the observation group in addition to the treatment in the control group. The anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and antral follicle count (AFC) serum levels were detected in both groups before the operation and at the first and third menstrual cycles postoperatively to evaluate ovarian function. Results: At the first and third menstrual cycles after surgery, the AMH, E2, and AFC serum levels in the two groups were significantly lower than before surgery, and the FSH and LH serum levels were higher than before surgery. The differences were statistically significant (P < 0.05). After the operation, AMH, E2, and AFC serum levels in the observation group were significantly higher than in the control group. FSH and LH serum levels were significantly lower than in the control group, and the differences were statistically significant (P < 0.05). Conclusion: For patients undergoing laparoscopic ovarian cystectomy, the adjuvant hyperbaric oxygen therapy could significantly improve the postoperative ovarian reserve function with remarkable effects.

A pandemic-induced environmental dilemma of disposable masks: solutions from the perspective of the life cycle.

The coronavirus disease 2019 (COVID-19) has swept the world and still afflicts humans. As an effective means of protection, wearing masks has been widely adopted by the general public. The massive use of disposable masks has raised some emerging environmental and bio-safety concerns: improper handling of used masks may transfer the attached pathogens to environmental media; disposable masks mainly consist of polypropylene (PP) fibers which may aggravate the global plastic pollution; and the risks of long-term wearing of masks are elusive. To maximize the utilization and minimize the risks, efforts have been made to improve the performance of masks (e.g., antivirus properties and filtration efficiency), extend their functions (e.g., respiration monitoring and acting as a sampling device), develop new disinfection methods, and recycle masks. Despite that, from the perspective of the life cycle (from production, usage, and discard to disposal), comprehensive solutions are urgently needed to solve the environmental dilemma of disposable masks in both technologies (e.g., efficient use of raw materials, prolonging the service life, and enabling biodegradation) and policies (e.g., stricter industry criteria and garbage sorting).

Identification of two-dimensional copper signatures in human blood for bladder cancer with machine learning.

Currently, almost all available cancer biomarkers are based on concentrations of compounds, often suffering from low sensitivity, poor specificity, and false positive or negative results. The stable isotopic composition of elements provides a different dimension from the concentration and has been widely used as a tracer in geochemistry. In health research, stable isotopic analysis has also shown potential as a new diagnostic/prognostic tool, which is still in the nascent stage. Here we discovered that bladder cancer (BCa) could induce a significant variation in the ratio of natural copper isotopes (65Cu/63Cu) in the blood of patients relative to benign and healthy controls. Such inherent copper isotopic signatures permitted new insights into molecular mechanisms of copper imbalance underlying the carcinogenic process. More importantly, to enhance the diagnostic capability, a machine learning model was developed to classify BCa and non-BCa subjects based on two-dimensional copper signatures (copper isotopic composition and concentration in plasma and red blood cells) with a high sensitivity, high true negative rate, and low false positive rate. Our results demonstrated the promise of blood copper signatures combined with machine learning as a versatile tool for cancer research and potential clinical application.

Phase transformation of silica particles in coal and biomass combustion processes.

Inhalation of respirable silica particles can cause serious lung diseases (e.g., silicosis and lung cancer), and the toxicity of respirable silica is highly dependent on its crystal form. Common combustion processes such as coal and biomass burning can provide high temperature environments that may alter the crystal forms of silica and thus affect its toxic effects. Although crystalline silica (i.e., quartz, tridymite, and cristobalite) were widely found at different temperatures during the burning processes, the sources and crystal transformation pathways of silica in the burning processes are still not well understood. Here, we investigate the crystal transformation of silica in the coal and biomass combustion processes and clarify the detailed transformation pathways of silica for the first time. Specifically, in coal burning process, amorphous silica can transform into quartz and cristobalite starting at 1100 °C, and quartz transforms into cristobalite starting at 1200 °C; in biomass burning process, amorphous silica can transform into cristobalite starting at 800 °C, and cristobalite transforms into tridymite starting at 1000 °C. These transformation temperatures are significantly lower than those predicted by the classic theory due to possibly the catalysis of coexisting metal elements (e.g., aluminum, iron, and potassium). Our results not only enable a deeper understanding on the combustion-induced crystal transformation of silica, but also contribute to the mitigation of population exposure to respirable silica.

The Protective Effects of Zornia diphylla (L.) Pers. Against Acute Liver Injury Induced by Carbon Tetrachloride in Mice.

Background: Zornia diphylla (L.) Pers. (ZDP) is a traditional Chinese herbal medicine that has been used for several decades to treat patients with liver diseases. Whether ZDP is best administered as a single agent or adjunctive therapy has yet to be determined as does the mechanism whereby it exerts its effects on antagonizing acute liver injury (ALI). Aim of the study: To investigate the protective effects of ZDP on ALI induced by carbon tetrachloride (CCl4) and the potential underlying mechanisms. Materials and Methods: Sixty adult mice were randomized into six study groups (n = 10/group). Three groups were treated with different concentrations of ZDP (2.5, 1.25, 0.625 g/kg), one with bifendate (0.0075 g/kg) alone (positive control) and one with physiologic saline (normal, negative control). All groups were treated for 14 days. Two hours after the last administration, the normal group received an intraperitoneal injection of peanut oil, and the other five groups received an intraperitoneal injection of an equal dose of CCl4 peanut oil solution. At 24 h, the liver index, histology and serum or tissue levels and/or protein expression of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), alkaline phosphatase (ALP), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione (GSH), Akt, phosphorylated Akt (p-Akt), nuclear factor kappa B p65 (NF-κB p65), inhibitor of NF-κB α (IκB-α), interleukin-1 ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), E-cadherin and vimentin were determined. Results: Compared to the model controls, the degree of inflammatory cell infiltration and hepatocyte injury of liver tissue was relieved in the bifendate and three ZDP groups; liver index in the ZDP (2.5, 1.25 g/kg) groups and serum liver function indices in the ZDP (2.5, 1.25 and 0.625 g/kg) groups were decreased; antioxidants SOD, CAT and GSH in liver tissue were increased but the lipid peroxidation index MDA was decreased; protein expression of inflammatory cytokines Akt, p-Akt, NF-κB p65, IκB-α, IL-1ß, IL-6 and TNF-α in the liver was ameliorated, and E-cadherin expression was increased. The results of liver histopathology also showed that ZDP had a significant effect on ALI. Conclusion: ZDP has obvious protective effects on CCl4-induced ALI as a single therapy and appears to act by inhibiting oxidation, reducing the release of inflammatory factors and promoting hepatocyte repair.

The Ciji-Hua'ai-Baosheng II Formula Attenuates Chemotherapy-Induced Anorexia in Mice With H22 Hepatocellular Carcinoma.

Background: Ciji-Hua'ai-Baosheng II Formula (CHB-II-F) is a traditional Chinese medicine formula, which specifically targets different aspects of chemotherapy-induced adverse effects in patients with cancer. In our clinical application, CHB-II-F significantly alleviated chemotherapy-induced anorexia (loss of appetite) and improved the quality of life for patients with tumor during and after chemotherapy. However, the mechanism of CHB-II-F in alleviation of chemotherapy-induced anorexia remains to be further investigated. Aim of Study: To explore the therapeutic effect and mechanism of CHB-II-F on chemotherapy-induced anorexia in the mice model of H22 hepatoma. Materials and Methods: A total of 72 Kunming mice of SPF grade were inoculated subcutaneously with H22 hepatoma cells into the right anterior armpit of the mice. After 1 week of seeding, mice were injected intraperitoneally with a high dose of 5-fluorouracil (200 mg/kg 5-FU) to establish the model of chemotherapy. The mice were randomly divided into six groups: untreated group, 5-FU group, 5-FU plus Yangzheng Xiaoji capsule (YZXJC) group, and three groups of 5-FU plus different concentrations of CHB-II-F. All the mice in each group were treated for 14 days. The body weight, food intake, tumor volume, and tumor weight of mice were measured, and pathological examinations of tumor tissue, stomach, and duodenum were carried out. Expressions of serum Leptin, Neuropeptide Y (NPY), epidermal cell growth factor (EGF), Motilin (MTL), Orexin A (OXA), Gastrin (GAS), Ghrelin, Prostaglandin E2 (PGE2), and jejunum superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were examined. The protein and mRNA levels of proopiomelanocortin (POMC), Orexin receptor 1 (OX1R), neuropeptide Y (NPY), cocaine and amphetamine regulated transcript peptide (CART), Agouti gene-related protein (AgRP), Leptin receptor (Ob-R), and Ghrelin receptor (GHSR) were examined in hypothalamus, and the protein levels of substance P (SP) and 5-hydroxytryptamine (5-HT) in duodenum were measured. Results: The combination of CHB-II-F and 5-FU could enhance the inhibitory effect of 5-FU on tumor. The tumor inhibition rates of 5-FU group, YZXJC group, CHB-II-F(H) group, CHB-II-F(M) group, and CHB-II-F(L) group were 58.88, 28.08, 54.96, 37.69, and 28.61%, respectively. Compared with untreated group and 5-FU group, CHB-II-F significantly increased the body weight and food intake of tumor-bearing mice; increased the content of NPY, Orexin A, Ghrelin, GAS, MTL, EGF, and PGE2 in serum and the activity of SOD in jejunum; and decreased the content of Leptin in serum and the content of MDA in jejunum. Compared with untreated group and 5-FU group, CHB-II-F also enhanced the expression of OX1R, GHSR, NPY, and AgRP protein and gene and decreased the expression of Ob-R, POMC, and CART protein and gene in hypothalamus of mice, and the gene expression was consistent with the protein expression. In addition, CHB-II-F decreased the expression of 5-HT and SP protein in duodenum. Conclusion: In the murine model of H22 hepatocellular carcinoma (HCC) receiving chemotherapy, CHB-II-F enhances the inhibitory effect of 5-FU on tumor, significantly improves the pathological injury of gastrointestinal tract caused by chemotherapy, and regulates the secretion of gastrointestinal hormones. It may alleviate chemotherapy-induced anorexia by affecting appetite regulatory factors in the feeding area of hypothalamus central nervous system and peripheral appetite regulatory factors.

Identification, Quantification, and Imaging of the Biodistribution of Soot Particles by Mass Spectral Fingerprinting.

Soot is ubiquitous and has large detrimental effects on climate, air quality, and human health. However, identification of soot in carbonaceous media is very challenging due to its nanoscale carbon nature and complex sources. Due to the shortage in the methodology, until now, the fate and health effect of soot particles after inhalation are still poorly understood. Here, we report a new method for label-free identification, quantification, and imaging of soot particles in complex media based on laser desorption/ionization mass spectrometry fingerprinting. We found that soot particles from different origins and with different morphologies showed highly consistent mass spectral fingerprints deriving from peak ratios of small carbon cluster anions (C2--C10-), which enabled both accurate quantification of soot in fine particulate matter (PM2.5) samples and label-free imaging of soot particles in biological media. By using this technique, we tracked and imaged the suborgan distribution of soot particles in mice after exposure to PM2.5. The results showed that the lung is the main target organ for short-term inhalation exposure to soot particles. This study helps to better understand the inhalation toxicology of soot and also provides a practical novel methodological platform for identification, tracing, and toxicological studies of elemental carbon-based nanomaterials.

Full-Endoscopic Lumbar Fusion Outcomes in Patients with Minimal Deformities: A Retrospective Study of Data Collected Between 2011 and 2015.

BACKGROUND: Open transforaminal lumbar interbody fusion (TLIF) is the gold standard treatment for back pain due to degenerative disc disease and lumbar instability. Traditional open TLIF has been associated with extensive tissue dissection, excessive blood loss, and slow recovery time. Full-endoscopic transforaminal lumbar interbody fusion (FE-TLIF) is an evolving treatment. OBJECTIVES: This study aims to review outcomes of FE-TLIF performed in an ambulatory surgery center (ASC) on patients with advanced disc disease with minimal spinal deformity. STUDY DESIGN: This study employed a retrospective cohort design. METHODS: This Western Institutional Review Board-approved study (#1-925640-1) assessed blood loss, operative time (OR time), post anesthesia care unit time (PACU time), and Visual Analog Scale (VAS) of 85 patients who underwent FE-TLIF between 2011 and 2015 and were followed up for 12 months. Relationships between risk factors (demographics, clinical presentation) and outcomes were analyzed. RESULTS: No intraoperative complications were observed. There were 2 cases of postoperative sympathetically mediated pain and 3 reoperations. The number of decompression/fusion levels was crucial to OR time but had a smaller impact on PACU time. OR time for patients with 2-level fusion was 110 minutes longer than for those with one level operation. BMI and age had no significant effect on OR time. BMI had a modest effect on PACU time. Gender and age did not affect PACU time. A significant decrease in VAS was observed. LIMITATIONS: This study has several limitations, including the lack of a control group and reliance on patient-reported outcomes (VAS). In addition, fusion rate and global sagittal alignment were not measured. Although not statistically significant, the use of facet screws, unilateral, or bilateral pedicle screws presented variation in techniques within the group. Early recovery also diminished the incentive for long-term follow-up. CONCLUSION: FE-TLIF is a feasible technique for lumbar stabilization surgery in an ASC in select patients. This level-II study demonstrates safety in a variety of clinical presentations, including obesity, extremes of age, and anatomical access challenge. Larger clinical series are necessary to validate this technique, particularly for the treatment of patients with advanced spinal deformities. KEY WORDS: Full-endoscopic, minimally invasive spine surgery, postoperative complications,TLIF, lumbar fusion, low back pain.

Safety Evaluation of a New Traditional Chinese Medical Formula, Ciji-Hua'ai-Baosheng II Formula, in Adult Rodent Models.

BACKGROUND: Ciji-Hua'ai-Baosheng II Formula (CHB-II-F) is a new traditional Chinese medical formula that has been shown to reduce toxicity and side effects of chemotherapy and increase the probability of cancer patient survival. Whether CHB-II-F is safe as an adjunctive therapy for cancer patients receiving chemotherapy has yet to be determined. PURPOSE: To evaluate the acute and subchronic toxic effects of CHB-II-F in rodent models. METHODS: In acute toxicity test, 24 Kunming mice were divided into 2 groups: untreated control and CHB-II-F 1.05 g/mL (31.44 g/kg) treated group. Treatment was administered to the treated group 3 times a day for 14 days. The overall health, adverse reactions, and mortality rate were documented. In subchronic toxicity test, 96 Sprague-Dawley rats were divided into 4 groups: untreated control, high dose CHB-II-F (H) (26.20 g/kg), medium dose CHB-II-F (M) (13. 10 g/kg), and low dose CHB-II-F (L) (6.55 g/kg) [equal to 24.375 g (dried medicinal herb)/kg] treated groups. Treated groups were given the treatments once a day for 4 weeks. The overall health and mortality rate were recorded every day. Body weight and food consumption were measured once a week. Hematologic and biochemical parameters, organ weights, and histopathologic markers were analyzed after 4 weeks. An additional 2 weeks were given as the treatment recovery period before end-point euthanization, and biochemical analyses were performed. RESULTS: The maximum tolerated dose (MTD) of CHB-II-F on mice was found to be 94.31 g/kg [equal to 351 g (dried medicinal herb)/kg], which is 108 times the human adult dose. In the acute toxicity test, administration of CHB-II-F 31.44 g/kg showed no adverse effect and did not cause mortality. In the subchronic toxicity test, after 4 weeks of treatment, compared to the controls, total cholesterol (TCHO) level, cardiac and splenic indexes, body weights of female rats, and mean corpuscular hemoglobin concentration (MCHC) in the CHB-II-F (H) group were significantly increased; triglyceride (TG) in the CHB-II-F (M) group and liver and splenic indexes in the CHB-II-F (L) group were increased. After the two-week recovery period, biofluid analyses, food consumption, and histopathologic examinations showed no abnormalities. CONCLUSION: Administration of CHB-II-F had no obvious adverse effect on the overall health of rodent models. A daily maximum dose of less than 94.31 g/kg or 6.55 g/kg CHB-II-F for 4 continuous weeks was considered safe.

Mifepristone inhibits proliferation, migration and invasion of HUUA cells and promotes its apoptosis by regulation of FAK and PI3K/AKT signaling pathway.

PURPOSE: The aim was to investigate mifepristone effects on endometrial carcinoma and the related mechanism. METHODS: HHUA cells were treated with DMEM containing different concentrations of mifepristone. HHUA cells treated with 100 µmol/L mifepristone were named the Mifepristone group. HHUA cells co-transfected with pcDNA3.1-PI3K and pcDNA3.1-AKT overexpression vectors were treated with 100 µmol/L mifepristone and named the Mifepristone + PI3K/AKT group. mRNA expression was detected by quantitative reverse transcription PCR. Protein expression was performed by Western blot. Cell proliferation was conducted by MTT assay. Wound-healing assay was conducted. Transwell was used to detect cells migration and invasion. Apoptosis detection was performed by flow cytometry. RESULTS: Mifepristone inhibited HHUA cells proliferation in a dose-dependent manner. Compared with HHUA cells treated with 0 µmol/L mifepristone, HHUA cells treated by 50-100 µmol/L mifepristone had a lower wound-healing rate, a greater number of migrating and invasive cells (P<0.01), as well as a higher percentage of apoptotic cells and Caspase-3 expression (P<0.01). When HHUA cells were treated with 50-100 µmol/L of mifepristone, FAK, p-FAK, p-PI3K and p-AKT relative expression was all significantly lower than HHUA cells treated with 0 µmol/L of mifepristone (P<0.01). Compared with the Mifepristone group, HHUA cells of the Mifepristone + PI3K/AKT group had a lower cell growth inhibition rate and percentage of apoptotic cells (P<0.01). CONCLUSION: Mifepristone inhibited HUUA cells proliferation, migration and invasion and promoted its apoptosis by regulation of FAK and PI3K/AKT signaling pathway.

The effects of Ciji-Hua'ai-Baosheng on immune function of mice with H22 hepatocellular carcinoma receiving chemotherapy.

BACKGROUND: Ciji-Hua'ai-Baosheng Decoction (CHBD) is a traditional Chinese formula that may attenuate the toxicity and side-effects of chemotherapy. The formula may also prolong the life of cancer patients. Whether CHBD should be employed as adjunctive therapy for cancer patients receiving chemotherapy has yet to be determined as does the mechanism whereby CHBD exerts its beneficial effects. AIM OF THE STUDY: To document the potential effects of CHBD on tumor growth and immune function in a murine model of hepatocellular carcinoma (HCC) receiving chemotherapy. MATERIALS AND METHODS: Sixty Kunming mice were injected subcutaneously with H22 hepatoma cells in the right anterior armpit. After seven days, the mice with formed tumors were injected with Cytoxan (CTX) (200 mg/kg) to establish the chemotherapy model. These mice were randomly divided into 5 groups: model (untreated controls), control (CTX,33.33 mg/kg), and high CHBD (H) (117 g/kg), moderate CHBD (M) (58.5 g/kg) and low CHBD (L) (29.25 g/kg) treated groups. Tumor weights and inhibitory ratio (decrease in tumor dimensions), histology of tumor, colon, spleen and liver, and biochemical tests of liver and kidney function were documented after 10 days. Serum and tumor IL-2, IFN-γ, IL-6, and TNF-α levels were determined by enzyme-linked immunosorbent assay (ELISA) and Western blot respectively. The potential bioactive compounds in CHBD were characterized by UHPLC-MS. RESULTS: Although tumor weights were decreased in CTX alone and CHBD (H) and CHBD (M) groups (-66%, -41% and -25% respectively), tumor cell density was reduced to the greatest extent in the CHBD (H) group. CHBD had no evident effects on liver and kidney function. CTX-induced colon inflammation and decrease in spleen lymphocytes were attenuated with CHBD treatment. CHBD increased serum IL-2, IFN-γ and TNF-α, but decreased IL-6 levels in serum and tumor tissue. UHPLC-MS analysis of CHBD revealed the presence of 11 bioactive compounds. CONCLUSIONS: In this murine model of HCC receiving chemotherapy, CHBD inhibited tumor growth, improved immune function and pro-inflammatory cytokine responses while attenuating CTX-associated side effects.

Development and Validation of a Prediction Model for Pain and Functional Outcomes After Lumbar Spine Surgery.

Importance: Functional impairment and pain are common indications for the initiation of lumbar spine surgery, but information about expected improvement in these patient-reported outcome (PRO) domains is not readily available to most patients and clinicians considering this type of surgery. Objective: To assess population-level PRO response after lumbar spine surgery, and develop/validate a prediction tool for PRO improvement. Design, Setting, and Participants: This statewide multicenter cohort was based at 15 Washington state hospitals representing approximately 75% of the state's spine fusion procedures. The Spine Surgical Care and Outcomes Assessment Program and the survey center at the Comparative Effectiveness Translational Network prospectively collected clinical and PRO data from adult candidates for lumbar surgery, preoperatively and postoperatively, between 2012 and 2016. Prediction models were derived for PRO improvement 1 year after lumbar fusion surgeries on a random sample of 85% of the data and were validated in the remaining 15%. Surgical candidates from 2012 through 2015 were included; follow-up surveying continued until December 31, 2016, and data analysis was completed from July 2016 to April 2017. Main Outcomes and Measures: Functional improvement, defined as a reduction in Oswestry Disability Index score of 15 points or more; and back pain and leg pain improvement, defined a reduction in Numeric Rating Scale score of 2 points or more. Results: A total of 1965 adult lumbar surgical candidates (mean [SD] age, 61.3 [12.5] years; 944 [59.6%] female) completed baseline surveys before surgery and at least 1 postoperative follow-up survey within 3 years. Of these, 1583 (80.6%) underwent elective lumbar fusion procedures; 1223 (77.3%) had stenosis, and 1033 (65.3%) had spondylolisthesis. Twelve-month follow-up participation rates for each outcome were between 66% and 70%. Improvements were reported in function, back pain, and leg pain at 12 months by 306 of 528 surgical patients (58.0%), 616 of 899 patients (68.5%), and 355 of 464 patients (76.5%), respectively, whose baseline scores indicated moderate to severe symptoms. Among nonoperative patients, 35 (43.8%), 47 (53.4%), and 53 (63.9%) reported improvements in function, back pain, and leg pain, respectively. Demographic and clinical characteristics included in the final prediction models were age, sex, race, insurance status, American Society of Anesthesiologists score, smoking status, diagnoses, prior surgery, prescription opioid use, asthma, and baseline PRO scores. The models had good predictive performance in the validation cohort (concordance statistic, 0.66-0.79) and were incorporated into a patient-facing, web-based interactive tool (https://becertain.shinyapps.io/lumbar_fusion_calculator). Conclusions and Relevance: The PRO response prediction tool, informed by population-level data, explained most of the variability in pain reduction and functional improvement after surgery. Giving patients accurate information about their likelihood of outcomes may be a helpful component in surgery decision making.

The Protective Effects of Ciji-Hua'ai-Baosheng II Formula on Chemotherapy-Treated H22 Hepatocellular Carcinoma Mouse Model by Promoting Tumor Apoptosis.

Ciji-Hua'ai-Baosheng II Formula (CHB-II-F) is a traditional Chinese medical formula that has been shown in clinical practice to relieve side effects of chemotherapy and improve quality of life for cancer patients. In order to understand the mechanism of its protective effects on chemotherapy, mice with transplanted H22 hepatocellular carcinoma were employed in this study. Ninety-two mice were injected subcutaneously with H22 HCC cell suspension into the right anterior armpit. After mice were treated with 5-fluorine pyrimidine (5-FU), they were divided into six groups as untreated group, 5-FU group, 5-FU plus Yangzheng Xiaoji Capsule group and three groups of 5-FU plus different concentrations of CHB-II-F. Twenty mice were euthanized after 7 days of treatment in untreated and medium concentration of CHB-II-F groups and all other mice were euthanized after 14 days of treatment. Herbal components/metabolites were analyzed by UPLC-MS. Tumors were evaluated by weight and volume, morphology of light and electron microscope, and cell cycle. Apoptosis were examined by apoptotic proteins expression by western blot. Four major components/metabolites were identified from serum of mice treated with CHB-II-F and they are ß-Sitosterol, Salvianolic acid, isobavachalcone, and bakuchiol. Treatment of CHB-II-F significantly increased body weights of mice and decreased tumor volume compared to untreated group. Moreover, CHB-II-F treatment increased tumor cells in G0-G1 transition instead of in S phase. Furthermore, CHB-II-F treatment increased the expression of pro-apoptotic proteins and decreased the expression anti-apoptotic protein. Therefore, CHB-II-F could improve mice general condition and reduce tumor cell malignancy. Moreover, CHB-II-F regulates apoptosis of tumor cells, which could contribute its protective effect on chemotherapy.

Direct modeling of near field thermal radiation in a metamaterial.

The study of near field thermal radiation is gaining renewed interest thanks in part to their great potential in energy harvesting applications. It is well known that plasmonic or polaritonic materials exhibit strongly enhanced fields near the surface, but it is not trivial to quantitatively predict their impact on thermal radiation intensity in the near field. In this paper, we present a case study for a metamaterial that supports a surface plasmon mode in the terahertz region and consequently exhibits strongly enhanced near field thermal radiation at the plasmon resonance frequency. We implemented a finite-difference time-domain method that thermally excites the metamaterial with randomly fluctuating dipoles according to the fluctuation-dissipation theorem. The calculated thermal radiation from the metamaterial was then compared with the case of optical excitation by the plane wave incident on the metamaterial surface. The optical excitation couples only to the mode that satisfies the momentum matching condition while thermal excitation is not bound by it. As a result, the near field thermal radiation exhibits substantial differences compared to the optically excited surface plasmon modes. Under thermal excitation, the near field intensity at 1 µm away from metal surface of the metamaterial reaches a maximum enhancement of 43 fold over the far field at the frequency of the Brillouin zone boundary mode while the near field intensity under optical excitation reaches a maximum enhancement of 24 fold at the frequency of the Brillouin zone center mode. In addition, the peak near field intensity under thermal excitation shows a 4-fold enhancement over blackbody radiation with linear polarization radiation in the far field. The ability to precisely predict the local field intensity under thermal excitation is critical to the development of advanced energy devices that take advantage of this near field enhancement and could lead to the development of new generation of novel energy technology.

[Influence of hot-humid stress and acclimation on airway mucus production in lungs of mice].

OBJECTIVE: To study the change of airway mucus secretion under a high temperature and humidity environment, and explore the effects of hot-humid stress and acclimation on the morbidity and mortality of respiratory disease. METHODS: Forty-five BABL/c mice were randomly divided into five groups:normal group, hot-humid group I, hot-humid group Ⅱ, hot-humid group Ⅲ, hot-humid group IV, with 9 mice in each group. Mice in normal group were continuously placed in the common environment and sacrificed after 7 days. Mice in other groups were housed in a temperature-and-humidity-controlled environment (33℃±0.5℃, 95%±5%). Mice in hot-humid group I, hot-humid group Ⅱ, hot-humid group Ⅲ and hot-humid group IV were sacrificed after 12 hours, 24 hours, 4 days, 7 days respectively. The protein expression of mucin 5AC(MUC5AC)、epidermal growth factor receptor (EGFR)、aquaporin 1(AQP1) and aquaporin 5(AQP5) in lung were tested by immunohistochemisty. RESULTS: After housed in a high temperature and humidity environment, immunohistochemisty revealed a significant increase of AQP5 12 h later, MUC5AC and EGFR 24 h later, compared with normal group(P<0.05). There was a significant decrease of MUC5AC 7 d later, compared with normal group(P<0.05). There was no significant difference in MUC5AC, EGFR and AQP5 expression among all groups at other time points. There was no difference of AQP1 in humid heat groups, compared with normal group, but a significant decrease in humid heat Ⅲ and IV groups, compared with humid heat I and Ⅱ groups. CONCLUSIONS: These findings indicate that hot-humid stress induces mucus hypersecretion in airways, which may be related to the up-regulation of EGFR and down-regulation of AQP5 in MUC5AC. Although acclimation mitigates above-mentioned response, a series of more complex responses may be induced if still in the hot-humid environment.

Effects of Ciji Hua'ai Baosheng granule formula (CHBGF) on life time, pathology, peripheral blood cells of tumor chemotherapy model mouse with H22 hepatoma carcinoma cells.

BACKGROUND: Ciji Hua'ai Baosheng Granule Formula (CHBGF) is a traditional Chinese empirical formula that can help the tumor patients who have received chemotherapy antagonize the toxin and side-effects so as to improve and prolong the life. This study is to evaluate the effects of CHBGF on improving life quality in terms of survival time, pathology of tumor tissue and ameliorating peripheral blood cells in mouse chemotherapy model with subcutaneous transplanted tumor or ascitic tumor of H22 hepatoma carcinoma cells at an overall level. MATERIALS AND METHODS: 71 mice among the 92 Kunming mice were injected subcutaneously into the right anterior armpit with H22 hepatoma carcinoma cells, after 7 days, which had formed tumors and were used peritoneal injection of Cytoxan (CTX) (200mg/kg) to establish the mouse chemotherapy model with transplanted tumor, and then which were commensurately divided into 8 groups by random digits table. 21 mice were injected into peritoneal cavity to use CTX and the same method to establish the model. The groups for evaluating the effects on the survival time were the model, CHBGF and positive control group respectively with 7 mice in each group. The groups for evaluating the effects on anti-cancer were the model group, three treatment groups and positive control group with 10 mice in each group. The survival-time-observing groups were given intragastric administration of normal saline, CHBGF (64g/kg) once a day, and peritoneal injection of 5-Fluorouracil (25mg/kg) once every other day respectively. The survival time of each group was observed. The five anti-cancer-observing groups were given intragastric administration of normal saline, CHBGF (64g/kg, 32g/kg and 16g/kg) once a day, and peritoneal injection of 5-Fluorouracil (25mg/kg) once every other day respectively. After treatment for 21 days, the transplanted tumors were peeled off. Blood was collected through pricking eyeball and analyzed by hematology analyzer. And postchemotherapy transplanted tumor inhibition ratios were calculated. Pathological changes of tumor tissues and blood smears were observed with light microscope. RESULTS: The life prolonging rate of CHBGF (64g/kg) group with transplanted tumor is 20.14%, and their survival time was longer than that of the 5-Fluorouracil group (P<0.05). Life prolonging rate of CHBGF (64g/kg) group with ascitic tumor is 64.15%, the survival time was longer than that of the model group (P<0.01) and the 5-Fluorouracil group (P<0.05). The growth of the transplanted tumor in model group was faster than that in CHBGF (64g/kg) group and 5-Fluorouracil group (P<0.05). The tumor average weight of the positive drug and the CHBGF (64g/kg, 32g/kg) groups was lighter than that of the model group (P<0.05 or P<0.01). The inhibition ratios of CHBGF (64g/kg, 32g/kg and 16g/kg) groups are 31.15%, 21.31%, and 13.11% respectively. Under light microscope, in the positive drug and three CHBGF groups the pathological deteriorated severity of tumor tissue observed was milder than that in the model group, the distribution of WBC in CHBGF groups was more obvious than that of the model and 5-Fluorouracil groups. The WBC and PLT decrease in CHBGF (64g/kg, 32g/kg and 16g/kg) groups is less than the model and the 5-Fluorouracil group (P<0.05 or P<0.01), the number of RBC and HGB just in the CHBGF (64g/kg) group was more than that of the model group or the 5-Fluorouracil group (P<0.05). CONCLUSION: Ciji Hua'ai Baosheng Granule Formula can prolong the survival time of the mice chemotherapy model of both subcutaneous transplanted tumor and ascitic tumor of H22 hepatoma carcinoma cells, has some determinate inhibitory effects on the growth of subcutaneous transplanted tumor chemo-treated, and has the therapeutic effect on antagonizing decrease of WBC and PLT caused by chemotherapy.

The Sinorhizobium meliloti LysR family transcriptional factor LsrB is involved in regulation of glutathione biosynthesis.

Glutathione, a key antioxidant in Sinorhizobium meliloti, is required for the development of alfalfa (Medicago sativa) nitrogen-fixing nodules. This tripeptide can be synthesized by both γ-glutamyl cysteine synthetase (GshA) and glutathione synthetase (GshB) in Escherichia coli and S. meliloti. Genetic evidence has indicated that the null mutant of S. meliloti gshA or gshB1 does not establish efficient symbiosis on alfalfa. However, the transcriptional regulation of gshA and gshB has not been well understood. Here, S. meliloti LsrB, a member of LysR family transcriptional factors, was found to positively regulate glutathione biosynthesis by activating the transcription of gshA and gshB1 under both free-living and symbiotic conditions. The decrease in glutathione production in the lsrB in-frame deletion mutant (lsrB1-2) was determined by using quadrupole time-of-flight liquid chromatography-mass spectrometry. The expression of gshA and gshB1 was correspondingly reduced in the mutant under free-living and symbiotic conditions by analyses of real-time quantitative reverse transcription-polymerase chain reaction and promoter-GUS fusions. Interestingly, LsrB positively regulated the transcription of oxyR, which encodes another member of LysR family regulators and responds to oxidative stresses in S. meliloti. The oxyR null mutant produced less glutathione, in which the transcription of gshA was consistently down-regulated. These findings demonstrate that glutathione biosynthesis is positively regulated by both LsrB and OxyR in S. meliloti.

Timing of palate repair affecting growth in complete unilateral cleft lip and palate.

OBJECTIVE: To evaluate the facial morphology characteristics of patients with complete unilateral cleft lip and palate (UCCLPs) who had undergone cleft palate repair at different times. DESIGN: This study included 46 nonsyndromic UCCLPs and 38 age and sex matched non-cleft patients. 35 cephalometric measurements were used to evaluate the facial morphology. Student's t-test, one-way ANOVA and rank sum tests were used for comparison. Significant difference was defined at 95% level. RESULTS: The data showed that UCCLPs who had palatoplasty between 7 and 12 years had greater PMP-A, PMP-ANS, Ba-ANS, Ba-A, Ba-N-ANS than those operated on before 4 years of age, and UCCLPs who had palatoplasty at 4-12 years had smaller Y-axis angle than those operated on before 4 years of age. CONCLUSIONS: The maxillary sagittal length increased gradually as von Langenbeck repair was delayed. UCCLPs who underwent palate repair using von Langenbeck technique at 4-12 years had a more protrusive maxilla and less clockwise rotated mandible than those repaired before 4 years. UCCLPs operated using the von Langenbeck technique at 4-12 years had better head-face morphology than those operated on before 4 years. There was no difference in facial morphology among UCCLPs with palate repair at 4-12 years.

Craniofacial morphology characteristics of operated unilateral complete cleft lip and palate patients in mixed dentition.

OBJECTIVE: The objective of this study was to analyze craniofacial morphologic characteristics at the stage of mixed dentition in Chinese children who had received surgery for unilateral complete cleft lip and palate (UCCLP) compared with the healthy population. MATERIAL AND METHODS: Lateral cephalometric radiographs were taken for 2 groups of individuals: (1) 48 UCCLP patients who had been operated on before 2 years of age, and (2) 60 noncleft peers as controls. RESULTS: The operated UCCLP groups differed from the control group as follows: reduced cranial base length, less maxillary length, more retrognathic maxilla, retusion of the entire maxilla, more incongruous intermaxillary relation, more concave skeletal profile, and more lingually inclined maxillary and mandibular incisors. CONCLUSIONS: The operated UCCLP children at the mixed dentition stage showed serious craniofacial deformities and the craniofacial growth was influenced (especially in maxilla).