Prenylated indole diketopiperazine alkaloids as phosphatase inhibitors from the marine-derived fungus Talaromyces purpureogenus.

Six previously undescribed prenylated indole diketopiperazine alkaloids, talaromyines A-F (1-6), were isolated from the marine-derived fungus Talaromyces purpureogenus SCSIO 41517. Their structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic data including NMR, HR-ESI-MS, and electronic circular dichroism calculations, together with chemical analysis of hydrolysates. Compounds 1-5 represent the first example of spirocyclic indole diketopiperazines biosynthesized from the condensation of L-tryptophan and L-alanine. Compounds 2 and 4-5 showed selective inhibitory activities against phosphatases TCPTP and MEG2 with IC50 value of 17.9-29.7 µM, respectively. Compounds 4-5 exhibited mild cytotoxic activities against two human cancer cell lines H1975 and HepG-2.

Microascones, Decahydrofluorene-Class Alkaloids from the Marine-Derived Fungus Microascus sp. SCSIO 41821.

Eight new decahydrofluorene-class alkaloids, microascones A and B (1 and 2), 2,3-epoxyphomapyrrolidone C (3), 14,16-epiascomylactam B (4), 24-hydroxyphomapyrrolidone A (5), and microascones C-E (6-8), along with five known analogs (9-13) were isolated from the marine-derived fungus Microascus sp. SCSIO 41821. Compounds 1 and 2 have an unprecedented complex macrocyclic alkaloid skeleton with a 6/5/6/5/6/5/13 polycyclic system. Their structures and absolute configurations were determined by spectroscopic analysis, quantum chemical calculations of ECD spectra, and 13C NMR chemical shifts. Compounds 10-13 showed selective enzyme inhibitory activity against PTPSig, PTP1B, and CDC25B, and 4, 9, and 10 exhibited strong antibacterial activity against seven tested pathogens. Their structure-bioactivity relationship was discussed, and a plausible biosynthetic pathway for 1-8 was also proposed.

Prediction of positive pulmonary nodules based on machine learning algorithm combined with central carbon metabolism data.

BACKGROUND: Lung cancer causes a huge disease burden, and early detection of positive pulmonary nodules (PPNs) as an early sign of lung cancer is extremely important for effective intervention. It is necessary to develop PPNs risk recognizer based on machine learning algorithm combined with central carbon metabolomics. METHODS: The study included 2248 participants at high risk for lung cancer from the Ma'anshan Community Lung Cancer Screening cohort. The Least Absolute Shrinkage and Selection Operator (LASSO) was used to screen 18 central carbon-related metabolites in plasma, recursive feature elimination (RFE) was used to select all 42 features, followed by five machine learning algorithms for model development. The performance of the model was evaluated using area under the receiver operator characteristic curve (AUC), accuracy, precision, recall, and F1 scores. In addition, SHapley Additive exPlanations (SHAP) was performed to assess the interpretability of the final selected model and to gain insight into the impact of features on the predicted results. RESULTS: Finally, the two prediction models based on the random forest (RF) algorithm performed best, with AUC values of 0.87 and 0.83, respectively, better than other models. We found that homogentisic acid, fumaric acid, maleic acid, hippuric acid, gluconic acid, and succinic acid played a significant role in both PPNs prediction model and NPNs vs PPNs model, while 2-oxadipic acid only played a role in the former model and phosphopyruvate only played a role in the NPNs vs PPNs model. This model demonstrates the potential of central carbon metabolism for PPNs risk prediction and identification. CONCLUSION: We developed a series of predictive models for PPNs, which can help in the early detection of PPNs and thus reduce the risk of lung cancer.

Effect of exposures to multiple metals on blood pressure and hypertension in the elderly: a community-based study.

A chronic disease, hypertension (HTN) is prevalent among the elderly. Exploring the factors that influence HTN and blood pressure (BP) changes is of great public health significance. However, mixed exposure to multiple serum metals has had less research on the effects on BP and HTN for the elderly. From April to August 2019, 2372 people participated in the community physical examination program for the elderly in Tongling City, Anhui Province. We measured BP and serum levels of 10 metals and collected basic demographic information. We analyzed the relationship between metal levels and changes in BP and HTN by the least absolute shrinkage and selection operator regression, Bayesian kernel machine regression model, and generalized linear model. In multiple models, lead (Pb) and cadmium (Cd) were still significantly associated with HTN occurrence after adjusting for potential confounders (Pb: ORquartile 4 VS quartile 1 = 1.20, 95% CI 1.01-1.43; Cd: ORquartile 4 VS quartile 1 = 1.37, 95% CI 1.16-1.62). In the male subgroup, results were similar to those of the general population. In the female group, Cd was positively correlated with HTN and systolic blood pressure, while Pb was not. According to this study, Pb and Cd were correlated with BP and HTN positively, and there was a certain joint effect. To some extent, our findings provide clues for the prevention of hypertension in the elderly.

Targeted metabolomics reveals the association between central carbon metabolism and pulmonary nodules.

With the widespread application of low-dose computed tomography (LDCT) technology, pulmonary nodules have aroused more attention. Significant alteration in plasma metabolite levels, mainly amino acid and lipid, have been observed in patients of PNs. However, evidence on the association between central carbon metabolism and PNs are largely unknown. The aim of this study was to investigate the underlying association of PNs and plasma central carbon metabolites. We measured the levels of 16 plasma central carbon metabolites in 1954 participants who gained LDCT screening in MALSC cohort. The inverse probability weighting (IPW) technique was used to control for bias due to self-selection for LDCT in the assessed high-risk population. The least absolute shrinkage and selection operator (LASSO) penalized regression was used to deal with the problem of multicollinearity among metabolites and the combined association of central carbon metabolites with PNs was estimated by using quantile g-computation (QgC) models. A quartile increase in 3-hydroxybutyric acid, gluconic acid, succinic acid and hippuric acid was positively associated with the PNs risk, whereas a quartile increase in 2-oxadipic acid and fumaric acid was negatively associated with the risk of PNs in multiple-metabolite models. A positive but insignificant joint associations of the mixture of 16 metabolites with PNs was observed by using QgC models analyses. Further studies are warranted to clarify the association between circulating metabolites and PNs and the biological mechanisms.

Corrigendum: The prognosis value of CONUT and SIS score for recurrent or metastatic esophageal squamous cell carcinoma patients treated with second-line immunotherapy.

[This corrects the article DOI: 10.3389/fonc.2023.1167625.].

Immune checkpoint inhibitors combined with or without radio(chemo)therapy for locally advanced or recurrent/metastatic esophageal squamous cell carcinoma.

OBJECTIVE: This study was designed to investigate the efficacy and prognostic factors for immune checkpoint inhibitors (ICIs) combined with or without radio(chemo)therapy and to evaluate their toxicity in patients with locally advanced or recurrent/metastatic esophageal squamous cell carcinoma (LA/RM ESCC). METHODS: In this study, 198 patients with locally advanced or recurrent/metastatic (LA/RM) ESCC who received ICIs combined with or without radiotherapy/chemotherapy in the Department of Radiotherapy of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. Univariate and multivariate analyses were performed to determine the prognostic factors for overall survival (OS) and progression free survival (PFS). The factors affecting treatment response and the occurrences of treatment-related adverse events (trAEs) were analyzed. RESULTS: The median OS and PFS were 30.4 months (95% confidence interval [CI] 15.1-45.7 months) and 15.3 months (95% CI 12.8-17.8 months), respectively. Univariate and multivariate analysis showed that the number of ICI cycles, the intervention of radiotherapy and dysphagia were independent factors affecting OS (Hazard ratio [HR] = 0.39, 2.043 and 0.365, respectively; P = 0.018, 0.001 and 0.032, respectively). The intervention of radiotherapy was an independent factor for PFS (hazard ratio [HR] = 18.149, P = 0.013). The median OS and PFS for patients who had complete response and partial response (Objective response, ORR) were 50.8 months (95% CI 25.8-75.7 months) and 20.5 months (95% CI 14.1-27.0), respectively, which were significantly higher than those in the non-ORR group (OSnon-ORR:17.5 months, 95% CI 14.0-21.0; χ2 = 13.881, P < 0.001; PFSnon-ORR: 12.1 months, 95% CI 10.1-14.1, χ2 = 10.676, P = 0.001). The intervention of radiotherapy could improve treatment response (χ2 = 47.725, P = 0.000). In entire study population, 83 patients (41.9%) had ≥ grade 2 trAEs. CONCLUSIONS: ICIs combined with radiotherapy/chemotherapy are safe and effective in LA/RM ESCC patients. Intervention of radiotherapy, the number of immunotherapy cycles and occurrence of dysphagia affecting the overall survival of LR/RM ESCC patients. Intervention of radiotherapy was an independent prognosis factor for OS and PFS and associated with better treatment response.

The prognosis value of CONUT and SIS score for recurrent or metastatic esophageal squamous cell carcinoma patients treated with second-line immunotherapy.

Objective: To investigate the predictive value of Controlling Nutritional Status (CONUT) score and systemic inflammation (SIS) score in the prognosis, short-term efficacy, and immune-related side effects of patient with recurrent or metastatic esophageal squamous cell carcinoma (R/M ESCC) receiving immunotherapy as second line therapy combined with or without radiotherapy. Methods: Forty-eight patients with R/M ESCC who received second-line therapy with Camrelizumab were retrospectively studied. They were divided into the high and low score groups according to the CONUT and SIS score. Univariate and multivariate analyses were used to analyze factors that might affect patient prognosis and the effects of different CONUT score and SIS on the short-term efficacy and immune-related toxic and side effects of patients. Results: The 1- and 2-year overall survival (OS) and progression-free survival (PFS) rates were 42.9% and 22.5%, and 29.0% and 5.8%, respectively. The CONUT score ranged from 0 to 6 (3.31 ± 1.43), whereas the SIS score ranged from 0 to 2 (1.19 ± 0.73). Multivariate analysis showed that treatment related toxicity, number of cycles of Camrelizumab used, short-term effect and SIS score were independent prognostic factors for OS (P=0.044, 0.021, 0.021, 0.030, respectively), whereas SIS and CONUT scores were independent prognostic factors for PFS (P=0.005, 0.047, respectively). Patients with low CONUT/SIS score had a low incidence rate of immune-related adverse reactions (X2 = 9.735, 5.693; P=0.002, 0.017) and better short-term efficacy (X2 = 4.427, 7.438; P=0.035, 0.006). Conclusion: R/M ESCC patients with low CONUT/SIS score have better prognosis, higher objective response rate, lower incidence of immune-related toxic and side effects after receiving immunotherapy as second-line therapy. CONUT scores and SIS scores may be reliable prognostic indicators for patient receiving immunotherapy as second-line therapy for R/M ESCC.

Construction of a predictive model of abdominal lymph node metastasis in thoracic esophageal squamous cell carcinoma and preliminary analysis of its effect on target for postoperative radiotherapy.

Purpose: To investigate the influencing factors of abdominal lymph node metastasis in thoracic esophageal squamous cell carcinoma (TESCC), and to construct its predictive model, in order to analyze the targets for postoperative radiotherapy. Methods and materials: From January 2008 to December 2014, the clinicopathological data of 479 patients who underwent radical resection for esophageal cancer in the Fourth Hospital of Hebei Medical University were collected and retrospectively analyzed. The influencing factors of postoperative abdominal lymph node metastasis were analyzed, and a predictive model was constructed based on their independent influencing factors. Receiver operating characteristic (ROC) curve was utilized to analyze the predictive value of this model; in the meantime, the postoperative locoregional recurrence (LRR) of this group was analyzed. Results: The postoperative pathology of all patients showed that the lymph node metastasis rate (LNR) was 39.7%, of which the abdominal lymph node metastasis rate was 22.0%. Logistic regression analysis revealed that the patient's lesion location, pN stage, vascular invasion, LND and mediastinal lymph node metastasis were independent risk factors for the positive rate of abdominal lymph nodes after surgery (P = 0.000, 0.000, 0.033, 0.000, 0.000). The probability of abdominal lymph node metastasis was Y = ex/(1 + ex), and X = -5.502 + 1.569 × lesion location + 4.269 × pN stage + 1.890 × vascular invasion + 1.950 × LND-4.248 × mediastinal lymph node metastasis. The area under the ROC curve (AUC) of this model in predicting abdominal lymph node metastasis was 0.962 (95% CI, 0.946-0.977). This mathematical model had a high predictive value for the occurrence of abdominal lymph node metastasis (P = 0.000), and the sensitivity and specificity of prediction were 94.6% and 88.3% respectively. The overall survival rate was significantly higher (X2 = 29.178, P = 0.000), while abdominal lymph node recurrence rate was lower in patients with negative abdominal lymph nodes than in those with negative lymph nodes (1.4%&7.7%, X2 = 12.254, P = 0.000). Conclusion: The lesion location, pN stage, vascular invasion, LND and mediastinal lymph node metastasis are independent influencing factors of abdominal lymph node metastasis in patients with TESCC. The mathematical model constructed by these indicators can accurately predict abdominal lymph node metastasis, which can help clinicians to choose the targets for postoperative radiotherapy.

Carotane sesquiterpenoids A-G from the desert endophytic fungus Fusarium sp. HM 166.

Seven undescribed carotane sesquiterpenoids named fusanoids A-G (1-7), along with one known analog (8) and two known sesterterpenes (9 and 10), were isolated from the fermentation broth of the desert endophytic fungi Fusarium sp. HM166. The structures of the compounds, including their absolute configurations, were determined by spectroscopic data, single-crystal X-ray diffraction analysis, and ECD calculations. Compound 10 showed cytotoxic activities against human hepatoma carcinoma cell line (Huh-7) and human breast cell lines (MCF-7 and MDA-MB-231), and compound 2 showed cytotoxic activity against MCF-7, while compounds 4-9 were inactive against all the tested cell lines. Compounds 4 and 10 showed potent inhibitory activities against the IDH1R132h mutant.

Endoscopic classification and pathological features of primary intestinal lymphangiectasia.

BACKGROUND: The appearance of the intestinal mucosa during endoscopy varies among patients with primary intestinal lymphangiectasia (PIL). AIM: To classify the endoscopic features of the intestinal mucosa in PIL under endoscopy, combine the patients' imaging and pathological characteristics of the patients, and explain their causes. METHODS: We retrospectively analyzed the endoscopic images of 123 patients with PIL who were treated at the hospital between January 1, 2007 and December 31, 2018. We compared and analyzed all endoscopic images, classified them into four types according to the endoscopic features of the intestinal mucosa, and analyzed the post-lymphographic computed tomography (PLCT) and pathological characteristics of each type. RESULTS: According to the endoscopic features of PIL in 123 patients observed during endoscopy, they were classified into four types: nodular-type, granular-type, vesicular-type, and edematous-type. PLCT showed diffuse thickening of the small intestinal wall, and no contrast agent was seen in the small intestinal wall and mesentery in the patients with nodular and granular types. Contrast agent was scattered in the small intestinal wall and mesentery in the patients with vesicular and edematous types. Analysis of the small intestinal mucosal pathology revealed that nodular-type and granular-type lymphangiectasia involved the small intestine mucosa in four layers, whereas ectasia of the vesicular- and edematous-type lymphatic vessels largely involved the lamina propria mucosae, submucosae, and muscular layers. CONCLUSION: Endoscopic classification, combined with the patients' clinical manifestations and pathological examination results, is significant and very useful to clinicians when scoping patients with suspected PIL.

Relationship between postoperative nodal skip metastasis of mid-thoracic esophageal squamous cell carcinoma and patient prognosis and its value in guiding postoperative adjuvant treatment.

Objective: To evaluate the predictive role of nodal skip metastasis (NSM) in the prognosis of lymph node-positive mid-thoracic esophageal squamous cell carcinoma, and to evaluate the significance of postoperative adjuvant treatment in patients with different sites of metastatic nodes. Methods: A retrospective analysis was performed on clinical data of 321 lymph node-positive mid-thoracic esophageal squamous cell carcinoma patients who underwent surgery in the Fourth Hospital of Hebei Medical University. Based on the site and condition of lymph node metastasis by postoperative pathology, the patients were divided into two groups: NSM group and non-NSM (NNSM) group. The propensity score matching (PSM) method was employed to match the two groups. The prognostic factors of patients before and after PSM as well as the effect of different adjuvant treatment modes on the prognosis of patients before and after PSM were analyzed. SPSS 29.0 statistical software was used for analysis. Results: PSM in a 1 : 1 matching ratio was performed, 103 patients were assigned to NSM group and NNSM group respectively. Significant differences were found in the 3- and 5-year OS and DFS between the two groups before PSM, the 3- and 5-year OS also showed a significant difference after PSM (P < 0.05). Multivariate analysis illustrated that gender, postoperative adjuvant treatment mode, N stage and lymph node metastasis were independent risk factors for OS and DFS after PSM (P < 0.05); for NSM patients, postoperative adjuvant chemotherapy and radiotherapy significantly prolonged OS and DFS before and after PSM (P < 0.05). But no significant difference was found in OS and DFS for NNSM patients after PSM (P > 0.05). Conclusion: Postoperative NSM is a good prognostic factor for patients with mid-thoracic esophageal squamous cell carcinoma, postoperative adjuvant chemoradiotherapy was recommended for those group, thereby gaining survival benefits.

Preliminary analysis of the benefits of different irradiation types on patients with postoperative locoregional recurrence of esophageal cell squamous carcinoma.

BACKGROUND: To explore the benefits of different types of irradiation on patients with postoperative locoregional recurrence (LRR) of thoracic esophageal squamous cell carcinoma (ESCC). METHODS: We analyzed the medical records of 344 patients with recurrent esophageal cancer (EC) at the Fourth Hospital of Hebei Medical University. All patients met an inclusion criteria that included having postoperative LRR (without distant metastasis), and having received either chemotherapy, radiotherapy, or chemoradiotherapy after LRR. Patients either received elective nodal irradiation (ENI) or involved field irradiation (IFI), with a stratified analysis performed on both groups. SPSS 19.0 software (IBM Corporation, Armonk, NY USA) was then used for statistical analysis. RESULTS: The median overall survival time of all patients after surgery was 33 months [95% confidence interval (CI): 28.3-37.7 months]; the median overall survival time of patients after recurrence after radiotherapy was 12.8 months (95% CI: 11.3-14.3 months). There were 276 cases (80.2%) of single local recurrence after surgery, and 68 cases (19.8%) of multiple local recurrence (≥2). The results of our multivariate analysis showed that the patient's gender, log odds of positive lymph nodes (LODDS), and the number of courses of chemotherapy were all independent factors affecting the patient's prognosis (P=0.003, P<0.001, and P<0.001). The results of stratified analysis showed that patients with esophageal lesion length <5.0 cm, stage N0, ≤9 surgically dissected lymph nodes, no positive regional lymph node metastasis (LNM), and LODDS ≤0.030 could benefit from ENI treatment (X2=4.208, P=0.032; X2=6.262, P=0.012; X2=10.359, P=0.001; X2=6.327, P=0.012; X2=6.026, P=0.014); and patients with ≥16 surgically dissected lymph nodes could benefit from IFI treatment (X2=4.429, P=0.035). CONCLUSIONS: Chemotherapy, radiotherapy, and chemoradiotherapy are all effective modes of treatment for patients with postoperative LRR of EC. Patients with shorter esophageal lesions determined by preoperative esophagography, earlier postoperative pathological N staging, lower LODDS scores, and fewer surgically dissected lymph nodes might benefit more from ENI treatment than from IFI. However, patients with a larger number of lymph nodes dissected during surgery might benefit more from IFI treatment. To further confirm this study's conclusions, multiple prospective studies should be undertaken in the future.

Talaromyoxaones A and B: Unusual Oxaphenalenone Spirolactones as Phosphatase Inhibitors from the Marine-Derived Fungus Talaromyces purpureogenus SCSIO 41517.

(+)- and (-)-talaromyoxaones A and B (1 and 2, respectively), two new oxaphenalenone derivatives with a hemiacetal frame and an unprecedented spirolactone frame of a 2'H,3H,4'H-spiro[isobenzofuran-1,3'-pyran]-3-one unit that show biosynthetic enantiodivergence, and two new oxaphenalenone analogues (±)-11-apopyrenulin (3) and (+)- or (-)-abeopyrenulin (4) were isolated from the marine-derived fungus Talaromyces purpureogenus SCSIO 41517. Their structures were elucidated by spectroscopic analysis, single-crystal X-ray diffraction, and quantum chemical calculations of ECD spectra. Compounds 1 and 2 showed selective inhibitory activity against phosphatases SHP1, SHP2, and MEG2 with IC50 values of 1.3-3.4 µM, and the potential modes of action for 1 were investigated by a preliminary molecular docking study.

Effect of SIB-IMRT-based selective dose escalation of local tumor on the prognosis of patients with esophageal cancer.

BACKGROUND: To investigate the effect of SIB-IMRT-based selective dose escalation to local tumor on the prognosis of patients with esophageal cancer (EC). METHODS: A total of 302 EC patients were enrolled. The prognostic factors of the entire group were initially analyzed, and the composition ratios of the two groups and the different doses of each fraction for PTV were compared. The propensity-score matching (PSM) was carried out (1:1 ratio), and the prognostic factors for the two groups were analyzed according to the results of COX. RESULTS: The median overall survival (OS) for all patients was 30.0 months (23.495-36.505 months), and the median disease-free survival (DFS) was 21.3 months (7.698-24.902 months). In multivariate analysis, chemotherapy, cTNM stage and dose-per-fraction for the PTV were independent prognostic factors for OS (P = 0.013, 0.000, 0.028) and DFS (P = 0.033, 0.000, 0.047). Multivariate analysis of patients after PSM revealed that cTNM staging and dose-per-fraction were the independent prognostic factors for OS (P = 0.000, 0.015). Chemotherapy, cTNM staging and dose-per-fraction for the PTV were the independent prognostic factors for DFS (P = 0.025, 0.010, 0.015). There was no significant difference in grade ≥ 2 acute toxicities between the two groups. A subgroup analysis of patients with a single dose of 2 Gy and > 2 Gy in the SIB-IMRT group showed that OS and DFS of the latter were significantly better than those of the former. CONCLUSION: The selective dose escalation to local tumors based on SIB-IMRT technique can improve the survival of patients received radical radiotherapy without increasing toxicities.

Clinical characteristics of systemic lupus erythematosus with chylothorax and/or chylous ascites: An analysis of 15 cases in China.

ABSTRACT: This analysis of clinical data from systemic lupus erythematosus (SLE) patients with chylothorax and/or chylous ascites was conducted to guide further clinical work.From June 2008 to June 2019, 15 SLE patients (14 females and 1 male) with chylothorax and/or chylous ascites were hospitalized at the Beijing Shijitan Hospital. Sixty SLE patients without chylothorax and chylous ascites were randomly selected as controls. Patients', clinical data was investigated.The mean age of onset of chylothorax and/or chylous ascites in patients with SLE was 35.7 ±â€Š3.7 years (range, 15-69 years). The mean disease duration of chylothorax and/or chylous ascites in patients with SLE was 13.7 ±â€Š3.4 months (range, 1-48 months). Patients with chylothorax and/or chylous ascites were always diagnosed at later stages of SLE compared with the controls. Among cases, glomerulonephritis and hematologic system involvement were the most common complications. Anti-Sjogren's syndrome antigen A antibody was positive in 7 cases (46.7%). Among cases, direct lymphangiography was performed in 13 patients, indicating thoracic duct outlet obstruction or a poor backflow at the terminal of the thoracic duct. Subsequently, 13 patients were treated with corticosteroids, combined with immunosuppressants in 11 patients and thoracic duct surgery in 6 patients. Eleven patients were followed up for 0.5 to 7.0 years. One patient died of infection. Eight patients (53.3%) achieved remission.Chylothorax and/or chylous ascites are rare complications of SLE. An early diagnosis and timely initiation of glucocorticoids, immunosuppressants, and surgery are critical to relieve symptoms and to improve prognosis.

Magnetic Curvatures of a Uniformly Magnetized Tesseroid Using the Cartesian Kernels.

In recent years, the gravitational curvatures, the third-order derivatives of the gravitational potential (GP), of a tesseroid have been introduced in the context of gravity field modeling. Analogous to the gravity field, magnetic field modeling can be expanded by magnetic curvatures (MC), the third-order derivatives of the magnetic potential (MP), which are the change rates of the magnetic gradient tensor (MGT). Exploiting Poisson's relations between ( n + 1 ) th-order derivatives of the GP and nth-order derivatives of the MP, this paper derives expressions for the MC of a uniformly magnetized tesseroid using the fourth-order derivatives of the GP of a uniform tesseroid expressed in terms of the Cartesian kernel functions. Based on the magnetic effects of a uniform spherical shell, all expressions for the MP, magnetic vector (MV), MGT and MC of tesseroids have been examined for numerical problems due to singularity of the respective integral kernels (i.e., near zone and polar singularity problems). For this, the closed analytical expressions for the MP, MV, MGT and MC of the uniform spherical shell have been provided and used to generate singularity-free reference values. Varying both height and latitude of the computation point, it is found numerically that the near zone problem also exists for all magnetic quantities (i.e., MP, MV, MGT and MC). The numerical tests also reveal that the polar singularity problems do not occur for the magnetic quantity as a result of the use of Cartesian as opposed to spherical integral kernels. This demonstrates that the magnetic quantity including the newly derived MC 'inherit' the same numerical properties as the corresponding gravitational functional. Possible future applications (e.g., geophysical information) of the MC formulas of a uniformly magnetized tesseroid could be improved modeling of the Earth's magnetic field by dedicated satellite missions.

Dosimetric Predictors of Radiation Gastritis Due to Postoperative Intensity Modulated Irradiation Therapy in Patients with Esophageal Squamous Cell Carcinoma After Radical Esophagectomy.

Objective: To explore the association between the incidence of acute radiation gastritis attributed to postoperative intensity modulated irradiation therapy (IMRT) and the dose volume of intrathoracic stomach of patients with esophageal squamous cell carcinoma (ESCC) after radical esophagectomy. Methods: The authors retrospectively collected the data of 49 ESCC patients who participated in postoperative IMRT treatment after radical esophagectomy, and analyzed the incidence of acute radiation gastritis during the treatment. Results: Among all the 49 patients, acute grade ≥2 radiation gastritis was observed in 19 patients (39%). Receiver operating characteristic (ROC) curve analysis showed that the physical variables, such as stomach Dmax, Dmean, length of the whole stomach received 5-40 Gy (LSTT5-LSTT40), and V10-V50, were associated with acute radiation gastritis. Patients were grouped according to cutoff values in physical indicators obtained from the ROC curve. Other than V5, the incidence of acute grade ≥2 radiation gastritis was significantly higher in the group with indicators above cutoff values than that below cutoff values, and the between-group difference was statistically significant in terms of physical indicators. Multivariate analysis suggested that LSTT5 and V40 could be acted as indicators to predict the incidence of acute grade ≥2 radiation gastritis. Conclusions: In the postoperative IMRT treatment for ESCC patients, protection of intrathoracic stomach is strongly recommended. Dose-volume histogram is a preferable predictive indicator for the occurrence of acute radiation gastritis, especially for the stomach LSTT5 and V40. Nevertheless, a larger sample size is needed to provide insight into the relevant study.

The browning of white adipose tissue and body weight loss in primary hyperparathyroidism.

BACKGROUND: Parathyroid hormone related protein (PTHrP) triggers white adipose tissue (WAT) browning and cachexia in lung cancer mouse models. It remains unknown whether excessive PTH secretion affects WAT browning and to what extent it contributes to body weight change in primary hyperparathyroidism (PHPT). METHODS: Using the adeno-associated virus injection, Pth gene over-expressed mice mimicking PHPT were firstly established to observe their WAT browning and body weight alteration. The association between PTH and body weight was investigated in 496 PHPT patients. The adipose browning activities of 20 PHPT and 60 control subjects were measured with PET/CT scanning. FINDINGS: Elevated plasma PTH triggered adipose tissue browning, leading to increased energy expenditure, reduced fat content, and finally decreased body weight in PHPT mice. Higher circulating PTH levels were associated with lower body weight (ß = -0.048, P = .0003) independent of renal function, serum calcium, phosphorus,and albumin levels in PHPT patients. PHPT patients exhibited both higher prevalence of detectable brown/beige adipose tissue (20% vs 3.3%, P = .03) and increased browning activities (SUV in cervical adipose was 0.77 vs 0.49,P = .02) compared with control subjects. INTERPRETATION: Elevated serum PTH drove WAT browning program, which contributed in part to body weight loss in both PHPT mice and patients. These results give insights into the novel pathological effect of PTH and are of importance in understanding the metabolic changes of PHPT. FUND: This research is supported by the National Key Research and Development Program of China and National Natural Science Foundation of China.

Quantitative determination and validation of octreotide acetate using 1 H-NMR spectroscopy with internal standard method.

Quantitative nuclear magnetic resonance (qNMR) is a well-established technique in quantitative analysis. We presented a validated 1 H-qNMR method for assay of octreotide acetate, a kind of cyclic octopeptide. Deuterium oxide was used to remove the undesired exchangeable peaks, which was referred to as proton exchange, in order to make the quantitative signals isolated in the crowded spectrum of the peptide and ensure precise quantitative analysis. Gemcitabine hydrochloride was chosen as the suitable internal standard. Experimental conditions, including relaxation delay time, the numbers of scans, and pulse angle, were optimized first. Then method validation was carried out in terms of selectivity, stability, linearity, precision, and robustness. The assay result was compared with that by means of high performance liquid chromatography, which is provided by Chinese Pharmacopoeia. The statistical F test, Student's t test, and nonparametric test at 95% confidence level indicate that there was no significant difference between these two methods. qNMR is a simple and accurate quantitative tool with no need for specific corresponding reference standards. It has the potential of the quantitative analysis of other peptide drugs and standardization of the corresponding reference standards.