Enhanced Production of Poly-γ-glutamic Acid by Bacillus subtilis Using Stage-controlled Fermentation and Viscosity Reduction Strategy.

In this study, the production of poly-γ-glutamic acid (PGA) by Bacillus subtilis using stage-controlled fermentation and viscosity reduction strategy was investigated in detail. Based on the single-factor optimization experiment, temperature (42 °C and 37 °C), pH (7.0 and uncontrolled), aeration rate (1.2 vvm and 1.0 vvm), and agitation speed (700 rpm and 500 rpm) were selected for the two-stage controlled fermentation (TSCF). The time points for the TSCF of temperature, pH, aeration rate, and agitation speed were set at 18.52 h, 2.82 h, 5.92 h, and 3.62 h, respectively, based on the kinetic analysis. A PGA titer of 19.79 ~ 22.17 g/L was obtained from the TSCF, which did not increase significantly than that (21.25 ± 1.26 g/L) of non-stage controlled fermentation (NSCF). This may be due to the high viscosity and low dissolved oxygen of the PGA fermentation broth. Thus, the TSCF combined with a viscosity reduction strategy was developed to further improve the production of PGA. The PGA titer reached 25.00 ~ 30.67 g/L, which increased by 17.66 ~ 32.94% to that of NSCF. This study provided a valuable reference for the development of process control strategies for high-viscosity fermentation systems.

Efficacy of breast reconstruction for N2-3M0 stage female breast cancer on breast cancer-specific survival: A population-based propensity score analysis.

BACKGROUND: The efficacy of breast reconstruction for patients with N2-3M0 stage female breast cancer (FBC) remained unclear due to the lack of randomized clinical trials. This retrospective study aimed to explore the efficacy of breast reconstruction for patients with N2-3M0 stage FBC. METHODS: Two thousand five hundred forty-five subjects with FBC staged by N2-3M0 from 2010 to 2016 were retrieved from the Surveillance, Epidemiology, and End Results database. Generalized boosted model (GBM) and propensity score matching (PSM) analyses and multivariable Cox analyses were employed to assess the clinical prognostic effect of postmastectomy reconstruction for patients with N2-3M0 stage FBC in breast cancer-specific survival (BCSS). RESULTS: Totally, 1784 candidates underwent mastectomy alone (mastectomy group), and 761 candidates underwent postmastectomy reconstruction (PMbR group), with 418 breast-specific deaths after a median follow-up time of 57 months (ranging from 7 to 227 months). BCSS in the mastectomy group showed no statistical difference from that in the PMbR group in the PSM cohort (HR = 0.93, 95% CI: 0.70-1.25, p = 0.400) and GBM cohort (HR = 0.75, 95% CI: 0.56-1.01, p = 0.057). In the multivariate analyses, there was no difference in the effect of PMbR and mastectomy on BCSS in the original cohort (HR = 0.85, 95% CI: 0.66-1.09, p = 0.197), PSM cohort (HR = 0.86, 95% CI: 0.64-1.15, p = 0.310), and GBM cohort (HR = 0.84, 95% CI: 0.61-1.17, p = 0.298). Triple-negative breast cancer (TNBC) was a detrimental factor affecting BCSS for patients in the PMbR group. CONCLUSIONS: Our study demonstrated that PMbR is an oncologically safe surgical treatment and can be widely recommended in clinics for females with non-TNBC staged by T0-3N2-3M0.

Global disease burden attributed to unsafe sex in 204 countries and territories from 1990 to 2019: results from the Global Burden of Disease Study 2019.

Unsafe sex has become a public safety problem that endangers society, and research on deaths and disability-adjusted life years (DALYs) related to unsafe sex is valuable for global policy-making. We aimed to estimate the deaths and DALYs attributable to unsafe sex by country, gender, age group, and sociodemographic status from 1990 to 2019. We extracted data on disease burden from the Global Disease Burden 2019 (GBD 2019) database for unsafe sex, including deaths, DALYs and age-standardized rates (ASRs). Comparative analyses were performed on data about deaths, DALYs and the responding ASRs attributable to unsafe sex in different countries and regions using the Social Demographic Index (SDI). The global age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) attributable to unsafe sex were 11.98 (95% uncertainty intervals (UI): 10.97-13.52) per 100,000 people and 570.78 (95% UI: 510.24-658.10) per 100,000 people, respectively. Both the ASMRs and ASDRs were the highest in southern sub-Saharan Africa and lowest in Australasia and decreased with increasing SDI levels. About unsafe-sex-related disease, HIV/AIDS has the highest ASMR [8.48 (95% UI: 7.62-9.95)/100,000 people] and ASDR [447.44 (95% UI: 394.82-533.10)/100,000 people], followed by Cervical cancer [ASMR: 3.40 (95% UI: 2.90-3.81)/100,000 people and ASDR: 107.2 (95% UI: 90.52-119.43)/100,000 people] and sexually transmitted infections excluding HIV [ASMR: 0.10 (95% UI: 0.08-0.11)/100,000 people and ASDR: 16.14 (95% UI: 10.51-25.83)/100,000 people]. The death and DALY burden caused by these three diseases were more serious in the over 75 years old age group. The 40-44 age group for men and the 35-39 age group for women had the highest population of unsafe sex-related deaths and DALYs, respectively. In addition, the burden of unsafe sex in women was more serious than those in men. Unsafe sex is an important risk factor for global disease burden and a leading cause of substantial health loss. We found that the risk of ASMRs and ASDRs attributable to unsafe sex had negative correlation with SDI levels. These results demonstrate that the need for revised policies that focus on efforts to reduce overall unsafe sex worldwide.

Nomogram for predicting overall survival in patients with invasive micropapillary carcinoma after breast-conserving surgery: A population-based analysis.

Background: Due to the loss of prediction of overall survival (OS) for patients with invasive micropapillary carcinoma (IMPC) after breast-conserving surgery (BCS), this study aimed to construct a nomogram for predicting OS in IMPC patients after BCS. Methods: In total, 481 eligible cases staged 0-III IMPC from 2000 to 2016 were retrieved from the SEER database. A nomogram was built based on the variables selected by LASSO regression to predict the 3-year and 5-year probabilities of OS. Results: A total of 336 patients were randomly assigned to the training cohort and 145 cases in the validation cohort. The LASSO regression revealed that six variables (age at diagnosis, AJCC stage, marital status, ER status, PR status, and chemotherapy) were predictive variables of OS, and then a nomogram model and an easy-to-use online tool were constructed. The C-indices 0.771 in the training cohort and 0.715 in the validation cohort suggested the robustness of the model. The AUC values for 3-year and 5-year OS in the training cohort were 0.782, 0.790, and 0.674, and 0.682 in the validation cohort, respectively. Based on the cutoff values of 147.23 and 222.44 scores calculated by X-tile analysis, participants in the low-risk group (≤147.23 scores) had a more favorable OS in comparison with those in the medium (>147.23, but <222.44 scores)- and high-risk groups (≥222.44 scores). Conclusions: By risk stratification, this model is expected to provide a precise and personalized prediction of the cumulative risk and guide treatment decision-making in improving OS strategies for IMPC patients.

Epidemiological trends of female breast and gynecologic cancers in adolescents and young adults in China from 1990 to 2019: Results from the Global Burden of Disease Study 2019.

Background: Research on the incidence, mortality, and disability-adjusted life years (DALYs) of female breast and gynecologic cancers (FeBGCs) and the relevant risk factors for adolescents and young adults (AYAs) are valuable for policy-making in China. We aimed to estimate the incidence, deaths, and DALYs and predict epidemiological trends of FeBGCs among AYAs in China between 1990 and 2019. Methods: Data from the 2019 Global Burden of Disease (GBD) study between 1990 and 2019 in 195 countries and territories were retrieved. Data about the number of FeBGC incident cases, deaths, DALYs, age-standardized rates (ASRs), and estimated annual percentage changes (EAPCs) were extracted. A comparative risk assessment framework was performed to estimate the risk factors attributable to breast cancer deaths and DALYs, and autoregressive integrated moving average (ARIMA) models were fitted for time-series analysis to predict female cancer morbidity and mortality among Chinese AYAs until 2030. Results: In 2019, there are 61,038 incidence cases, 8,944 deaths, and 529,380 DALYs of FeBGCs among the AYAs in China, respectively. The estimated annual percentage change (EAPC) values were positive scores (>0) in ASIRs and negative scores (<0) in ASMR and ASDR. Furthermore, in 2030, the incidence rate of FeBGCs would grow to 30.49 per 100,000 in China, while the mortality rate would maintain a steady state. Of the deaths and DALYs, diet high in red meat was the greatest contributor to breast cancer, while a high body mass index (BMI) was the greatest contributor to cervical, ovarian, and uterine cancers. Conclusion: The increasing Chinese FeBGC burden is mainly observed in AYAs and non-red meat diet, and the control of body weight could reduce FeBGC burden in China.

Effect of the Nipple-Excising Breast-Conserving Therapy in Female Breast Cancer: A Competing Risk Analysis and Propensity Score Matching Analysis of Results Based on the SEER Database.

Introduction: Due to the lack of randomized controlled trial, the effectiveness and oncological safety of nipple-excising breast-conserving therapy (NE-BCT) for female breast cancer (FBC) remains unclear. We aimed to explore and investigate the prognostic value of NE-BCT versus nipple-sparing breast-conserving therapy (NS-BCT) for patients with early FBC. Methods: In this cohort study, data between NE-BCT and NS-BCT groups of 276,661 patients diagnosed with tumor-node-metastasis (TNM) stage 0-III FBC from 1998 to 2015 were retrieved from the Surveillance, Epidemiology, and End Results database. Propensity score matching analysis, Kaplan-Meier, X-tile, Cox proportional hazards model, and competing risk model were performed to evaluate the effectiveness and oncological safety for patients in NE-BCT and NS-BCT groups. Results: A total of 1,731 (0.63%) patients received NE-BCT (NE-BCT group) and 274,930 (99.37%) patients received NS-BCT (NS-BCT group); 44,070 subjects died after a median follow-up time of 77 months (ranging from 1 to 227 months). In the propensity score matching (PSM) cohort, NE-BCT was found to be an adversely independent prognostic factor affecting overall survival (OS) [hazard ratio (HR), 1.24; 95% CI, 1.06-1.45, p=0.0078]. Subjects in NE-BCT group had similar breast-cancer-specific survival (BCSS) (HR, 1.15; 95%CI, 0.88-1.52, p=0.30) and worse other-causes-specific death (OCSD) (HR, 1.217; 95%CI, 1.002-1.478, p=0.048<0.05) in comparison with those in the NS-BCT group. Conclusions: Our study demonstrated that the administration of NE-BCT is oncologically safe and reliable and can be widely recommended in clinics for women with non-metastatic breast cancer.

Research on the cutoff tumor size of omitting radiotherapy for BCSS after breast conserving surgery in women aged 65 years or oder with low-risk invasive breast carcinoma: Results based on the SEER database.

BACKGROUND: Radiotherapy after breast-conserving surgery (BCS) is not always necessary in older women staged T1N0M0 with low-risk invasive breast cancer, but few studies have concluded the detailed tumor size as a reference for avoiding radiotherapy. The study was conducted to explore and identify the optimal cutoff tumor size. METHODS: The study population was from the Surveillance, Epidemiology, and End Results (SEER) database in 2010-2016. Propensity score matching was used to balance the confounders between groups. Predictors associated with survival were analyzed by Kaplan-Meier, X-tile, Cox proportional hazards model and competing risk model. RESULTS: A total of 52049 women and 3846 deaths were included in the cohort with a median follow-up of 34 months. Based on the cutoff value determined by X-tile analysis, the study population were divided into small tumor group (≤14 mm in diameter) and large tumor group (>14 mm in diameter). Small tumors and radiotherapy were correlated with better breast cancer-specific survival (BCSS). In subgroup analysis, the absolute benefit of BCSS in 6 years attributed to radiotherapy was only 0.90% (RT vs. non- RT:98.77% vs. 97.87%) for patients with small tumors but up to 3.33% (RT vs. non- RT:97.10% vs. 93.77%) for those with large tumors. CONCLUSION: Small tumors and adjuvant radiotherapy were associated with improved long-term prognosis, and 14 mm in diameter was the cutoff tumor size of omitting radiotherapy for patients aged 65 or older with T1N0M0 stage, ER+ and HER2-breast carcinoma after BCS.

Nomogram Predicts the Role of Contralateral Prophylactic Mastectomy in Male Patients With Unilateral Breast Cancer Based on SEER Database: A Competing Risk Analysis.

BACKGROUND: Contralateral prophylactic mastectomy (CPM) in female breast cancer (FBC) is supported by multiple clinical studies and consensus guidelines, but knowledge of preventive contralateral mastectomy in male breast cancer (MaBC) is very limited and its benefits are still controversial. METHODS: A retrospective cohort study was enrolled with 4,405 MaBC patients who underwent unilateral mastectomy (UM) or CPM from the Surveillance, Epidemiology, and End Results (SEER) database from 1998 to 2015. A nomogram was built based on the corresponding parameters by competing risks regression to predict the 3-year, 5-year, and 8-year probabilities of BCSD (breast cancer-specific death). C-index and calibration curves were chosen for validation. Net reclassification index (NRI) and integrated discrimination improvement (IDI) were used to estimate the nomogram's clinical utility. RESULTS: A total of 4,197 patients received UM and 208 patients received CPM, with 63-months median follow-up. In the competing risks regression, six variables (surgery, marital status, T-stage, N-stage, histology, tumor grade) were significantly associated with BCSD. Based on these independent prognosis factors, a nomogram model was constructed. The C-index 0.75 (95%CI: 0.73-0.77) in the training cohort and 0.73 (95%CI: 0.71-0.74) in the internal validation group suggested robustness of the model. In addition, the calibration curves exhibited favorably. The NRI values (training cohort: 0.54 for 3-year, 0.55 for 5-year, and 0.49 for 8-year BCSD prediction; validation cohort: 0.51 for 3-year, 0.45 for 5-year, and 0.33 for 8-year BCSD prediction) and IDI values (training cohort: 0.02 for 3-year, 0.03 for 5-year, and 0.04 for 8-year BCSD prediction; validation cohort: 0.02 for 3-year, 0.04 for 5-year, and 0.04 for 8-year BCSD prediction) indicated that the model performed better than the AJCC criteria-based tumor staging alone. CONCLUSIONS: The administration of CPM was associated with the decrease in risk of BCSD in patients with MaBC. The nomogram could provide a precise and personalized prediction of the cumulative risk in patients with MaBC after CPM.

Research on the Role of Marriage Status Among Women Underwent Breast Reconstruction Following Mastectomy: A Competing Risk Analysis Model Based on the SEER Database, 1998-2015.

BACKGROUND: Marital status is an important foundation of social public relations in modern society, but little is known about the role of marriage status among women who underwent breast reconstruction following mastectomy. This research mainly aimed to investigate the prognostic value of marital status in breast cancer women who underwent breast reconstruction. METHODS: The demographic and clinical data of patients were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program database. The eligible population was assessed on overall survival (OS), breast cancer-specific survival (BCSS), and breast cancer-specific death (BCSD) through propensity score matching (PSM) method, multivariate Cox proportional hazards model analysis, competing risk model analysis, multivariate competing risk regression model analysis, and subgroup analysis. RESULTS: Of the 54,683 women included in the current study, a total of 38,110 participants were married patients (married group), and 16,573 participants were unmarried patients (unmarried group). Patients in the married group tended to have better OS (hazard ratio [HR] = 1.397, 95% CI: 1.319-1.479, p < 0.001), BCSS (HR = 1.332, 95% CI: 1.244-1.426, p < 0.001), cumulative BCSD incidence (Gray's test, p < 0.001), and other causes-specific death (OCSD) incidence (Gray's test, p < 0.001) than those in the unmarried group. In subgroup analysis, subjects with HR+/HER2- subtype breast cancer in the married group showed improved OS (1.589, 95% CI: 1.363-1.854, p < 0.001) and BCSS (HR = 1.512, 95% CI: 1.255-1.82, p < 0.001) than those in the unmarried group. CONCLUSIONS: Our study demonstrated that the inexistence of marriage was associated with poorer OS and BCSS, especially for HR+/HER2- breast cancer women who underwent breast reconstruction.

Research on the Role of Combined Chemotherapy and Radiotherapy in Patients With N+ Non-Metastatic Metaplastic Breast Carcinoma: A Competing Risk Analysis Model Based on the SEER database, 2000 to 2015.

PURPOSE: Due to the rarity of metaplastic breast carcinoma (MpBC), no randomized trials have investigated the role of combined chemotherapy and radiotherapy (CCRP) in this condition. We aimed to explore and identify the effectiveness of CCRP in patients with regional lymph node metastasis (N+) non-metastatic MpBC. MATERIALS AND METHODS: Data were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program database. We assessed the effects of CCRP on overall survival (OS), breast cancer-specific survival (BCSS), and breast cancer-specific death (BCSD) using Kaplan-Meier analysis, competing risk model analysis, and competing risk regression mode analysis. RESULTS: A total of 707 women and 361 death cases were included in the unmatched cohort, of which 76.45% (276/361) were BCSD, and 23.55% (85/361) were non-breast cancer-specific deaths (non-BCSD). Both the ChemT and CCRP groups had better OS (ChemT group: HR: 0.59, 95% CI: 0.45-0.78, P<0.001; CCRP group: HR: 0.31, 95% CI: 0.23-0.41, P<0.001) and BCSS (ChemT group: HR: 0.63, 95% CI: 0.45-0.87, P<0.001; CCRP group: HR: 0.32, 95%CI: 0.22-0.46, P<0.001) than the non-therapy group. Subjects in the CCRP group tended to have significantly lower cumulative BCSD (Gray's test, P=0.001) and non-BCSD (Gray's test, P<0.001) than the non-therapy group or ChemT group. In competing risk regression model analysis, subjects in the CCRP group had a better prognosis in BCSD (HR: 0.710, 95% CI: 0.508-0.993, P=0.045) rather than the ChemT group (HR: 1.081, 95% CI: 0.761-1.535, P=0.660) than the non-therapy group. CONCLUSION: Our study demonstrated that CCRP could significantly decrease the risk of death for both BCSD and non-BCSD and provided a valid therapeutic strategy for patients with N+ non-metastatic MpBC.

Evaluation of the Hepa Wash® treatment in pigs with acute liver failure.

BACKGROUND: Mortality of patients with acute liver failure (ALF) is still unacceptably high. Available liver support systems are still of limited success at improving survival. A new type of albumin dialysis, the Hepa Wash® system, was newly introduced. We evaluated the new liver support system as well as the Molecular Adsorbent Recycling System (MARS) in an ischemic porcine model of ALF. METHODS: In the first study animals were randomly allocated to control (n=5) and Hepa Wash (n=6) groups. In a further pilot study, two animals were treated with the MARS-system. All animals received the same medical and surgical procedures. An intraparenchymal intracranial pressure was inserted. Hemodynamic monitoring and goal-directed fluid therapy using the PiCCO system was done. Animals underwent functional end-to-side portacaval shunt and ligation of hepatic arteries. Treatment with albumin dialysis was started after fall of cerebral perfusion pressure to 45 mmHg and continued for 8 h. RESULTS: All animals in the Hepa Wash group survived the 13-hour observation period, except for one that died after stopping treatment. Four of the control animals died within this period (p=0.03). Hepa Wash significantly reduced impairment of cerebral perfusion pressure (23±2 vs. 10±3 mmHg, p=0.006) and mean arterial pressure (37±1 vs. 24±2 mmHg, p=0.006) but had no effect on intracranial pressure (14±1 vs. 15±1 mmHg, p=0.72). Hepa Wash also enhanced cardiac index (4.94±0.32 vs. 3.36±0.25 l/min/m2, p=0.006) and renal function (urine production, 1850 ± 570 vs. 420 ± 180 ml, p=0.045) and eliminated water soluble (creatinine, 1.3±0.2 vs. 3.2±0.3 mg/dl, p=0.01; ammonia 562±124 vs. 1382±92 µg/dl, p=0.006) and protein-bound toxins (nitrate/nitrite 5.54±1.57 vs. 49.82±13.27 µmol/l, p=0.01). No adverse events that could be attributed to the Hepa Wash treatment were observed. CONCLUSIONS: Hepa Wash was a safe procedure and improved multiorgan system failure in pigs with ALF. The survival benefit could be the result of ameliorating different organ functions in association with the detoxification capacity of water soluble and protein-bound toxins.