Clinical characteristics and radiation therapy modality of younger patients with early-stage endometrial cancer, a multicenter study in China's real world.

BACKGROUND: Endometrial cancer is a prevalent gynecologic malignancy found in postmenopausal women. However, in the last two decades, the incidence of early-stage has doubled in women under 40 years old. This study aimed to investigate the clinical and pathological characteristics and adjuvant therapeutic modalities of both young and not -young patients with early-stage endometrial cancer in China's real world. METHODS: This retrospective study analyzed patients with early-stage endometrial cancer at 13 medical institutions in China from 1999 to 2015. The patients were divided into two groups: young (≤ 45 years old) and non-young (> 45 years old). Statistical comparisons were conducted between the two groups for clinical characteristics, pathological features, and survival. The study also identified factors that affect local recurrence-free survival (LRFS) using Cox proportional risk regression analysis. Propensity score matching (1:1) was used to compare the effects of local control between vaginal brachytherapy (VBT) alone and pelvic external beam radiotherapy (EBRT) ± VBT. RESULTS: The study involved 1,280 patients, 150 of whom were 45 years old or younger. The young group exhibited a significantly higher proportion of stage II, low-risk, lower uterine segment infiltration (LUSI), and cervical invasion compared to the non-young group. Additionally, the young patients had significantly larger maximum tumor diameters. The young group also had a significantly higher five-year overall survival (OS) and a five-year LRFS. Age is an independent risk factor for LRFS. There was no significant difference in LRFS between young patients with intermediate- to high-risk early-stage endometrial cancer who received EBRT ± VBT and those who received VBT alone. CONCLUSIONS: In the present study, young patients had better characteristics than the non-young group, while they exhibited higher levels of aggressiveness in certain aspects. The LRFS and OS outcomes were better in young patients. Age is an independent risk factor for LRFS. Additionally, VBT alone may be a suitable option for patients under 45 years of age with intermediate- to high-risk early-stage endometrial cancer, as it reduces the risk of toxic reactions and future second cancers while maintaining similar local control as EBRT.

Comparative assessment of emulsifiers for in vitro ruminal gas production and fermentation measurements: Tween 80 is a suitable emulsifier.

Emulsifiers are essential for achieving a homogenous distribution of lipophilic supplements in in vitro rumen fluid incubations. Since emulsifiers can alter rumen fermentation, it is crucial to select one that minimally impacts fermentation parameters to reduce potential biases. This study aimed to evaluate seven emulsifiers' impact on in vitro ruminal fermentation using the Hohenheim Gas Test in order to identify the most inert emulsifier. Rumen fluids were collected from three non-lactating Original Brown-Swiss cannulated cows before morning feeding and incubated for 24 h with a basal diet in triplicates. The emulsifiers tested were ethanol, ethyl acetate, propylene glycol, glycerol, ethylene glycol, soy lecithin, and Tween® 80, each in two dosages (0.5% or 1% v/v). The untreated basal diet served as control. Compared to control, in vitro organic matter digestibility was enhanced by ethyl acetate (by 36.9 and 48.2%), ethylene glycol (by 20.6 and 20.1%), glycerol (by 46.9 and 56.8%) and soy lecithin (by 19.7 and 26.8%) at 0.5 and 1% dosage, respectively. Additionally, the 24-h methane production increased for ethanol (by 41.9 and 46.2%), ethylene glycol (by 50.5 and 51.5%), and glycerol (by 63.1 and 65.4%) for the 0.5 and 1% dosage, respectively, and 0.5% dosage for ethyl acetate (by 31.6%). The acetate molar proportion was 17.2%pt higher for ethyl acetate, and 25.5%pt lower for glycerol at 1% dosage, compared to the control. The propionate concentration was 22.1%pt higher 1% glycerol, and 15.2%pt and 15.1%pt higher for 0.5 and 1% propylene glycol, respectively, compared to the control. In summary, Tween® 80 did not significantly affect in vitro rumen fermentation parameters, making it the most suitable choice for in vitro incubations involving lipophilic substances in rumen fluid. Ethanol may be considered as an alternative emulsifier if methane production is not the variable of interest.

Practice patterns of adjuvant radiotherapy in women with stage I to II endometrial carcinoma: a real-world multi-institutional analysis in China.

BACKGROUND: This study aimed to report clinical practice patterns of postoperative radiotherapy for stage I to II endometrial carcinoma (EC) patients treated in 13 Chinese medical centers. METHODS: We included early stage EC patients treated by hysterectomy and adjuvant RT between 2003 and 2017 from 13 institutions. Patients were classified into 4 risk groups based on ESMO-ESGO-ESTRO recommendations (2014). RESULTS: A total of 1,227 cases were analyzed. Along the 15 years of the study, an increasing tendency was found towards administration for vaginal brachytherapy (VBT) alone, while the proportion of external beam pelvic radiotherapy (EBRT) alone remained stable in the corresponding period. When radiation modalities were stratified by risk groups, proportion of VBT alone significantly increased in all risk groups. The higher the risk, the later VBT became the main adjuvant treatment modality. However, EBRT alone or with VBT remained the main adjuvant method for high-risk patients. There were 13 dose-fractionation schemes for VBT alone with the scheme of 30 Gy in 6 fractions prescribed at 0.5cm under the vaginal mucosa accounting for most. There were 17 schemes for VBT boost and the most common schedule was 10 Gy in 2 fractions. The upper 3-5cm part of vagina was the most frequent target. 89.6% of the practitioners performed two-dimensional VBT technique. The median dose for EBRT was 50 Gy. From 2003 to 2017, conventional radiotherapy was gradually replaced by three-dimensional conformal radiotherapy modality and intensity modulated radiotherapy. CONCLUSION: We report a significant shift from EBRT to VBT alone for high-intermediate-risk, intermediate-risk and low-risk EC patients from 2003 to 2017 while EBRT remained the main radiation modality for high-risk early stage patients. There has been remarkable heterogeneity among VBT dose fractionation schedules across China. TRIAL REGISTRATION: The clinical trial ID was ChiCTR-PRC-17010712. It was authorized by the Institutional Review Board of Peking Union Medical College Hospital (N0. S-K139).

Effect of diets enriched in n-6 or n-3 fatty acids on dry matter intake, energy balance, oxidative stress, and milk fat profile of transition cows.

The objective of this study was to determine the effect of dietary supplementation of n-3 polyunsaturated fatty acids (PUFA) and n-6 PUFA on dry matter intake (DMI), energy balance, oxidative stress, and performance of transition cows. Forty-five multiparous Holstein dairy cows with similar parity, body weight (BW), body condition score (BCS), and milk yield were used in a completely randomized design during a 56-d experimental period including 28 d prepartum and 28 d postpartum. At 240 d of pregnancy, cows were randomly assigned to one of the 3 isoenergetic and isoprotein dietary treatments, including a control ration containing 1% hydrogenated fatty acid (CON), a ration with 8% extruded soybean (HN6, high n-6 PUFA source), and a ration with 3.5% extruded flaxseed (HN3; high n-3 PUFA source). The HN6 and HN3 diets had an n-6/n-3 ratio of 3.05:1 and 0.64:1 in prepartum cows and 8.16:1 and 1.59:1 in postpartum cows, respectively. During the prepartum period (3, 2, and 1 wk before calving), DMI, DMI per unit of BW, total net energy intake, and net energy balance were higher in the HN3 than in the CON and NH6 groups. During the postpartum period (2, 3, and 4 wk after calving), cows fed HN3 and HN6 diets both showed increasing DMI, DMI as a percentage of BW, and total net energy intake compared with those fed the CON diet. The BW of calves in the HN3 group was 12.91% higher than those in the CON group. Yield and nutrient composition of colostrum (first milking after calving) were not affected by HN6 or HN3 but milk yield from 1 to 4 wk of milking was significantly improved compared with CON. During the transition period, BW, BCS, and BCS changes were not affected. Cows fed the HN6 diet had a higher plasma NEFA concentration compared with the CON cows during the prepartum period. Feeding HN3 reduced the proportion of de novo fatty acids and increased the proportion of preformed long-chain fatty acids in regular milk. In addition, the n-3 PUFA-enriched diet reduced the n-6/n-3 PUFA ratio in milk. In conclusion, increasing the n-3 fatty acids concentration in the diet increased both DMI during the transition period and milk production after calving, and supplementing n-3 fatty acids was more effective in mitigating the net energy balance after calving.

Overview of adjuvant radiotherapy on survival, failure pattern and toxicity in stage I to II endometrial carcinoma: a long-term multi-institutional analysis in China.

BACKGROUND: This research aimed to provide an overview of the impact of adjuvant vaginal brachytherapy (VBT) and external beam pelvic radiotherapy (EBRT) with or without VBT on survival in stage I to II EC patients in China from a long-term multi-institutional analysis. METHODS: We retrospectively analyzed stage I to II EC patients from 13 institutions treated between 2003 and 2015. All patients underwent surgical staging and received adjuvant RT. Patients were divided into groups of low-risk (LR), intermediate-risk (IR), high-intermediate-risk (HIR) and high-risk (HR). Survival statistics, failure pattern, and toxicity of different radiation modalities in different risk groups were analyzed. RESULTS: A total of 1048 patients were included. HR disease represented 27.6%, HIR 17.7%, IR 27.7% and LR 27.1%, respectively. Endometrioid adenocarcinoma (EAC) and non-endometrioid carcinoma (NEC) accounted for 92.8 and 7.2%. A total of 474 patients received VBT alone and 574 patients received EBRT with or without VBT. As for EAC patients, the 5-year overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) rate was: 94.6, 90.4, 93.0 and 91.6%, respectively. For LR patients, EBRT (with or without VBT) seemed to be a risk factor. With the higher risk category, the survival benefit of EBRT gradually became remarkable. EBRT (with or without VBT) significantly increased DFS, LRFS and DMFS compared to VBT alone in the HR group (p < 0.05). Distant metastasis was the main failure pattern for all risk groups. As for NEC patients, the 5-year OS, DFS, LRFS and DMFS rate was: 93.4, 87.2, 91.7 and 89.3%, respectively. As for toxicity, EBRT (with or without VBT) significantly increased the incidence of grade 1-2 gastrointestinal, urinary, and hematological toxicity. CONCLUSIONS: For stage I to II EC patients, EAC accounted for the majority and had better prognosis than NEC. For EAC patients, VBT alone resulted in comparable survival to EBRT in the LR, IR and HIR groups, while EBRT significantly increased survival in the HR group. EBRT had higher rate of toxicity than VBT.

Hydroxy-selenomethionine supplementation promotes the in vitro rumen fermentation of dairy cows by altering the relative abundance of rumen microorganisms.

AIMS: This study aims to investigate the effect of hydroxy-selenomethionine supplementation on the in vitro rumen fermentation characteristics and microorganisms of Holstein cows. METHODS AND RESULTS: Five fermentation substrates, including control (without selenium supplementation, CON), sodium selenite supplementation (0.3 mg kg-1 DM, SS03), and hydroxy-selenomethionine supplementation (0.3, 0.6 and 0.9 mg kg-1 DM, SM03, SM06 and SM09, respectively) were incubated with rumen fluid in vitro. The results showed that in vitro dry matter disappearance and gas production at 48 h was significantly higher in SM06 than SM03, SS03 and CON; propionate and total volatile fatty acid (VFA) production was higher in SM06 than CON. Moreover, higher species richness of rumen fluid was found in SM06 than others. Higher relative abundance of Prevotella and Prevotellaceae-UCG-003 and lower relative abundance of Ruminococcus-1 were detected in SM06 than CON. Besides, higher relative abundance of Ruminococcaceae_UCG-005 was found in CON than other treatments. CONCLUSIONS: It is observed that 0.6 mg kg-1 DM hydroxy-selenomethionine supplementation could increase cumulative gas production, propionate, and total VFAs production by altering the relative abundance of Prevotella, Prevotellaceae-UCG-003, Ruminococcaceae_UCG-005 and Ruminococcus-1, so that it can be used as a rumen fermentation regulator in Holstein cows. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides an optimal addition ratio of hydroxy-selenomethionine on rumen fermentation and bacterial composition via an in vitro test.

Treatment optimization of pelvic external beam radiation and/or vaginal brachytherapy for patients with stage I to II high-risk Endometrioid adenocarcinoma: a retrospective multi-institutional analysis.

BACKGROUND: For stage I to II high-risk endometrioid adenocarcinoma patients, the optimal adjuvant radiotherapy modality remains controversial. The present study sought to optimize the treatment of pelvic external beam radiation (EBRT) with/or vaginal brachytherapy (VBT) for high-risk endometrioid adenocarcinoma patients in multiple radiation oncology centers across China. METHODS: This article retrospectively reviewed stage I to II patients with resected endometrioid adenocarcinoma treated at 13 radiation centers from 1999 to 2015. Patients were eligible if they had high-risk features (stage IB Grade 3 disease or stage II Grade 1-3 disease) on the basis of ESMO-ESGO-ESTRO risk group consensus. RESULTS: A total of 218 patients were included. Fifty-one patients received EBRT, 25 patients received VBT, and 142 patients were administered EBRT combined with VBT. The three groups were comparable in baseline characteristics, except the proportion of stage IB and Grade 3 disease in the VBT group was significantly higher and their age was older. Survival analysis showed that OS, DFS, LRFS and DMFS were significantly different among the three groups. Two out of three groups were compared with each other, and results demonstrated that DFS, LRFS and DMFS were worse in the VBT group than in the EBRT or EBRT + VBT group. The 3-year OS rates were 95.2, 85.2 and 95.1% in the EBRT, VBT and EBRT + VBT groups, respectively (p = 0.043). There was no significant difference in survival outcomes between EBRT group and EBRT + VBT group. A propensity matching analysis was performed to eliminate group differences. The results demonstrated that DFS and LRFS were significantly improved in the pelvic radiation group compared to the VBT group. Distant failure accounted for most of the failure patterns. Patients in the VBT group had significantly increased local and regional recurrence rates than patients in the EBRT or EBRT + VBT group. Acute and chronic radiation-induced toxicities were well tolerated for all patients. CONCLUSION: For patients with postoperative stage I to II high-risk endometrioid adenocarcinoma, compared with VBT alone, radiotherapy modalities including EBRT significantly improved DFS, LRFS and DMFS with tolerable adverse effects. Overall survival was not significantly different between EBRT and EBRT + VBT modalities.

A Multi-Institutional Retrospective Analysis of Oncologic Outcomes for Patients With Locally Advanced Cervical Cancer Undergoing Platinum-Based Adjuvant Chemotherapy After Concurrent Chemoradiotherapy.

OBJECTIVE: To evaluated the oncologic outcomes associated with platinum-based adjuvant chemotherapy following concurrent chemoradiotherapy (CCRT) in the management of patients with locally advanced cervical cancer (LACC). METHODS: A total of 695 patients with FIGO stage IB2, IIA2, IIB-IVA LACC treated at 6 medical facilities were enrolled and divided into 2 groups: 478 were assigned to CCRT alone (CCRT group) and 217 to adjuvant chemotherapy after CCRT (CCRT-ACT group). The treatment outcomes were retrospectively compared and reported after the propensity score matching (PSM) analysis. RESULTS: With a median follow-up of 56.4 months, no statistically significant differences were found in overall survival (OS), disease-free survival (DFS), progression-free survival (PFS) and distance metastasis-free survival (DMFS) between 2 groups. In CCRT-ACT group, patients with lymph nodes involvement or squamous cell carcinoma (SCC) had significantly longer DMFS, but no significant benefit in survival outcomes were observed with more than 2 cycles of adjuvant chemotherapy. Moreover, patients with a high level of CA125 (>20.5U/mL) or SCC-Ag (>22.8µg/L) had a relatively better DFS or PFS, and grade 3-4 acute hematological toxicity, late urinary and lower gastrointestinal complications and diarrhea symptom were more frequent in CCRT-ACT group. CONCLUSIONS: Adjuvant chemotherapy after CCRT has a potential role in further improving disease control for LACC patients with lymph nodal-metastasis or SCC with a high level of CA125 or SCC-Ag. Due to increased treatment-related complications and diarrhea symptom affecting the quality of life, post-CCRT adjuvant chemotherapy with excessive cycles was not be considered as the most appropriate choice in general.

Advancements in the Understanding of Small-Cell Neuroendocrine Cervical Cancer: Where We Stand and What Lies Ahead.

Small-cell neuroendocrine cervical carcinoma (SCNCC) is a rare yet aggressive gynecological malignancy associated with dismal clinical outcomes. Its rarity has led to a limited number of retrospective studies and an absence of prospective research, posing significant challenges for evidence-based treatment approaches. As a result, most gynecologic oncology centers have limited experience with this tumor, emphasizing the urgent need for a comprehensive review and summary. This article systematically reviews the pathogenesis, immunohistochemical and molecular characteristics, prognostic factors, and clinical management of gynecologic SCNCC. We specifically focused on reviewing the distinct genomic characteristics of SCNCC identified via next-generation sequencing technologies, including loss of heterozygosity (LOH), somatic mutations, structural variations (SVs), and microRNA alterations. The identification of these actionable genomic events offers promise for discovering new molecular targets for drug development and enhancing therapeutic outcomes. Additionally, we delve deeper into key clinical challenges, such as determining the optimal treatment modality between chemoradiation and surgery for International Federation of Gynecology and Obstetrics (FIGO) stage I phase patients within a precision stratification framework, as well as the role of targeted therapy within the homologous recombination (HR) pathway, immune checkpoint inhibitors (ICIs), and prophylactic cranial irradiation (PCI) in the management of SCNCC. Finally, we anticipate the utilization of multiple SCNCC models, including cancer tissue-originated spheroid (CTOS) lines and patient-derived xenografts (PDXs), to decipher driver events and develop individualized therapeutic strategies for clinical application.

Attitudes and behavior of radiation oncologists toward sexual issues of cervical cancer patients who receive radiation therapy: a survey in China.

OBJECTIVE: Cervical cancer is known to impair women's sexual function. This study aimed at investigating the attitudes and behavior of radiation oncologists regarding sexual functioning of female cervical cancer patients who receive radiation therapy. METHODS: A total of 186 radiation oncologists were included. A self-reported questionnaire was used to investigate the attitudes and behavior of radiation oncologists. The oncologists were queried on their history of consultation on sexual issues, attitudes, and behavior toward sexual issues and considerations of sexual life for cervical cancer patients who receive radiotherapy. RESULTS: Among 120 radiation oncologists who completed the questionnaires, 101 (84.2%) had been consulted on sexual issues, of whom only 29 (24.2%) were consulted by more than 10% of cervical cancer patients who received radiation therapy or their families. Compared with those without a history of consultation, radiation oncologists with a history of consultation were more likely to agree that "radiation oncologists should deal with a patient's sexual issues" (88.1% vs 68.4%) and disagree that "sex is private and should not be interfered with" (66.2% vs 44.5%). Five radiation oncologists (4.2%) had received special training to deal with the sexual issues of cervical cancer patients who receive radiotherapy, and 112 oncologists (93.3%) did not have any information on sexual functioning to give the their patients. CONCLUSIONS: History of consultation on sexual issues affects radiation oncologists' attitudes and behavior toward sexual issues of cervical cancer patients. Radiation oncologists should have a more positive attitude toward sexual issues and should receive more specific relevant training.

[Predictive value of the maximum aggregation rate of platelet for septic shock and septic shock with disseminated intravascular coagulation].

OBJECTIVE: To investigate the predictive value of the maximum aggregation rate (MAR) of platelet for septic shock and septic shock with disseminated intravascular coagulation (DIC). METHODS: A retrospective case-control study enrolled patients with sepsis admitted to department of critical care medicine of the First Affiliated Hospital of Zhengzhou University from January 2021 to November 2022. The basic data, dynamic platelet aggregation rate, blood routine, inflammation indicators, sequential organ failure assessment (SOFA) and other clinical indicators within 24 hours after admission were collected. Septic patients were divided into the shock group and the non-shock group according to the presence of septic shock; then refer to the International Society on Thrombosis and Hemostasis (ISTH) standard, patients with septic shock were divided into the shock DIC group and the shock non-DIC group according to the presence of dominant DIC. Compared the differences in platelet aggregation function between these groups, and the receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of the MAR for septic shock and septic shock with DIC. Spearman correlation analysis was used to analyze the correlation of MAR with inflammation indicators and the severity of illness in patients with sepsis. RESULTS: A total of 153 sepsis patients were included and 61 with septic shock (including 17 with dominant DIC and 44 without dominant DIC). Compared with the non-shock group, the level of procalcitonin (PCT), C-reactive protein (CRP), and SOFA score were significantly higher in the shock group [PCT (mg/L): 6.90 (2.50, 23.50) vs. 0.87 (0.26, 5.75), CRP (mg/L): 156.48 (67.11, 230.84) vs. 90.39 (46.43, 182.76), SOFA score: 11.00 (8.00, 14.00) vs. 5.00 (3.00, 8.00), all P < 0.05]. The platelet count (PLT) and the MAR induced by adenosine diphosphate (ADP), adrenaline (A), collagen (COL), and arachidonic acid (AA; ADP-MAR, A-MAR, COL-MAR, AA-MAR) in the shock group were significantly decreased [PLT (×109/L): 101.00 (49.00, 163.50) vs. 175.50 (108.25, 254.50), ADP-MAR: 28.50% (22.00%, 38.05%) vs. 45.90% (33.98%, 60.28%), A-MAR: 38.90% (30.00%, 55.40%) vs. 65.15% (54.38%, 72.53%), COL-MAR: 27.90% (20.85%, 36.55%) vs. 42.95% (33.73%, 54.08%), AA-MAR: 24.70% (16.40%, 34.20%) vs. 46.55% (28.33%, 59.20%), all P < 0.05]. Subgroup analysis revealed that, compared with the shock non-DIC group, the SOFA scores were significantly higher in patients in the shock DIC group (13.29±5.23 vs. 10.39±3.58, P < 0.05), the PLT and COL-MAR in the shock DIC group were significantly reduced [PLT (×109/L): 36.00 (22.00, 67.50) vs. 115.50 (84.25, 203.75), COL-MAR: 21.50% (17.85%, 32.60%) vs. 30.95% (22.98%, 38.53%), all P < 0.05]. ROC curve analysis showed that A-MAR had a higher predictive value for septic shock, and the area under the ROC curve (AUC) was 0.814 [95% confidence interval (95%CI) was 0.742-0.886, P = 0.000]. When the optimal cut-off value was 51.35%, the sensitivity was 68.9%, the specificity was 82.6%, the positive predictive value was 0.724 and the negative predictive value was 0.800. COL-MAR had some predictive value for septic shock with DIC, and the AUC was 0.668 (95%CI was 0.513-0.823, P = 0.044). When the optimal cut-off value was 21.90%, the sensitivity was 52.9%, the specificity was 79.5%, the positive predictive value was 0.500, and the negative predictive value was 0.813. Spearman correlation analysis showed that the MAR induced by each inducer was negatively correlated with inflammatory indicators and SOFA scores in sepsis patients, with A-MAR showing the strongest correlation with SOFA score (r = -0.327, P = 0.000). CONCLUSIONS: MAR, an indicator of platelet aggregation function, shows predictive value for septic shock and septic shock with DIC, and it could be used to for evaluating the severity of patients with sepsis. In addition, tt also can be used as a monitoring index to predict the changes of sepsis patients and to guide the treatment.

[Analysis of lymphocyte subsets in patients with sepsis and its impact on prognosis].

OBJECTIVE: To explore the characteristics of changes in peripheral blood lymphocyte subsets in patients with sepsis in intensive care unit (ICU) and analyze their predictive value for prognosis. METHODS: The clinical data of sepsis patients admitted to the surgical intensive care unit (SICU) of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021 were analyzed retrospectively. The patients met the diagnostic criteria of Sepsis-3 and were ≥ 18 years old. Peripheral venous blood samples were collected from all patients on the next morning after admission to SICU for routine blood test and peripheral blood lymphocyte subsets. According to the 28-day survival, the patients were divided into two groups, and the differences in immune indexes between the two groups were compared. Logistic regression analysis was used to analyze the risk factors of immune indexes that affect prognosis. RESULTS: (1) A total of 279 patients with sepsis were enrolled in the experiment, of which 198 patients survived at 28 days (28-day survival rate 71.0%), and 81 patients died (28-day mortality 29.0%). There were no significant differences in age (years old: 57.81±1.71 vs. 54.99±1.05) and gender (male: 60.5% vs. 63.6%) between the death group and the survival group (both P > 0.05), and the baseline data was comparable.(2) Acute physiology and chronic health evalution II (APACHE II: 22.06±0.08 vs. 14.08±0.52, P < 0.001), neutrophil percentage [NEU%: (88.90±1.09)% vs. (84.12±0.77)%, P = 0.001], procalcitonin [PCT (µg/L): 11.97±2.73 vs. 5.76±1.08, P = 0.011], platelet distribution width (fL: 16.81±0.10 vs. 16.57±0.06, P = 0.029) were higher than those in the survival group, while lymphocyte percentage [LYM%: (6.98±0.78)% vs. (10.59±0.86)%, P = 0.012], lymphocyte count [LYM (×109/L): 0.70±0.06 vs. 0.98±0.49, P = 0.002], and platelet count [PLT (×109/L): 151.38±13.96 vs. 205.80±9.38, P = 0.002], and thrombocytocrit [(0.15±0.01)% vs. (0.19±0.07)%, P = 0.012] were lower than those in the survival group. (3) There was no statistically significant difference in the percentage of lymphocyte subsets between the death group and the survival group, but the absolute value of LYM (pieces/µL: 650.24±84.67 vs. 876.64±38.02, P = 0.005), CD3+ absolute value (pieces/µL: 445.30±57.33 vs. 606.84±29.25, P = 0.006), CD3+CD4+ absolute value (pieces/µL: 239.97±26.96 vs. 353.49±18.59, P = 0.001), CD19+ absolute value (pieces/µL: 111.10±18.66 vs. 150.30±10.15, P = 0.049) in the death group was lower than those in the survival group. Other lymphocyte subsets in the death group, such as CD3+CD8+ absolute value (pieces/µL: 172.40±24.34 vs. 211.22±11.95, P = 0.112), absolute value of natural killer cell [NK (pieces/µL): 101.26±18.15 vs. 114.72±7.64, P = 0.420], absolute value of natural killer T cell [NKT (pieces/µL): 33.22±5.13 vs. 39.43±2.85, P = 0.262], CD4-CD8- absolute value (pieces/µL: 41.07±11.07 vs. 48.84±3.31, P = 0.510), CD4+CD8+ absolute value (pieces/µL: 3.39±1.45 vs. 3.47±0.36, P = 0.943) were not significantly different from those in the survival group. (4)Logistic regression analysis showed that lymphocyte subsets were not selected as immune markers with statistical significance for the prognosis of sepsis. CONCLUSIONS: The changes of immune indexes in sepsis patients are closely related to their prognosis. Early monitoring of the above indexes can accurately evaluate the condition and prognosis of sepsis patients.

[Expression level of cytokines in patients with sepsis and its effect on prognosis].

OBJECTIVE: To observe the expression level of cytokines in patients with sepsis and its effect on prognosis. METHODS: The clinical data of sepsis patients admitted to the intensive care unit (ICU) of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were analyzed retrospectively, including gender, age, and acute physiology and chronic health evaluation II (APACHE II), blood routine, procalcitonin (PCT), C-reactive protein (CRP), and cytokines levels [interleukins (IL-2, IL-4, IL-6, IL-10, IL-17), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ)] within 24 hours of admission to ICU. The 28-day prognosis of the patients was followed up. The patients were divided into survival group and death group according to the prognosis. The clinical data between the two groups of sepsis patients with different prognosis were compared. Binary Logistic regression analysis was used to analyze the independent risk factors affecting the prognosis of patients with sepsis, and the receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of each risk factor for the prognosis of patients with sepsis. RESULTS: (1) A total of 227 patients with sepsis were enrolled, including 168 patients in the survival group (survival rate 74.0%) and 59 patients in the death group (mortality 26.0%). There were no significant differences in age (years old: 55.97±2.13 vs. 54.67±1.11) and gender (male: 71.2% vs. 57.1%) between the death group and the survival group (both P > 0.05), indicating that the baseline data of the two groups were comparable. (2) The APACHE II (19.37±0.99 vs. 14.88±0.61, P < 0.001) and PCT (µg/L: 12.39±2.94 vs. 4.14±0.90, P < 0.001) in the death group were significantly higher than those in the survival group, while the platelet count [PLT (×109/L): 144.75±12.50 vs. 215.99±11.26, P = 0.001] and thrombocytocrit [(0.14±0.01)% vs. (0.19±0.01)%, P = 0.001] were significantly lower than those in the survival group. (3) The level of IL-6 in the death group was significantly higher than that in the survival group (ng/L: 577.66±143.16 vs. 99.74±33.84, P < 0.001). There were no statistically significant differences in other cytokines, IL-2, IL-4, IL-10, TNF-α, IFN-γ and IL-17 between the death group and the survival group [IL-2 (ng/L): 2.44±0.38 vs. 2.63±0.27, P = 0.708; IL-4 (ng/L): 3.26±0.67 vs. 3.18±0.34, P = 0.913; IL-10 (ng/L): 33.22±5.13 vs. 39.43±2.85, P = 0.262; TNF-α (ng/L): 59.33±19.21 vs. 48.79±29.87, P = 0.839; IFN-γ (ng/L): 6.69±5.18 vs. 1.81±0.16, P = 0.100; IL-17 (ng/L): 2.05±0.29 vs. 2.58±0.33, P = 0.369]. (4) Binary Logistic regression analysis showed that APACHE II and IL-6 were independent risk factors affecting the prognosis of patients with sepsis [odds ratio (OR) and 95% confidence interval (95%CI) were 1.050 (1.008-1.093) and 1.001 (1.000-1.002), P values were 0.019 and 0.026, respectively]. (5) ROC curve analysis showed that APACHE II and IL-6 had certain predictive value for the prognosis of patients with sepsis, the area under the ROC curve (AUC) was 0.754 (95%CI was 0.681-0.827) and 0.592 (95%CI was 0.511-0.673), P values were < 0.001 and 0.035, respectively. When the optimal cut-off value of APACHE II was 16.50 score, the sensitivity was 72.6% and the specificity was 69.9%. When the optimal cut-off value of IL-6 was 27.87 ng/L, the sensitivity was 67.2% and the specificity was 52.8%. CONCLUSIONS: APACHE II score and IL-6 level have certain predictive value for the prognosis of patients with sepsis, the higher APACHE II score and IL-6 level, the greater the probability of death in patients with sepsis.

Diagnostic performance and clinical impact of blood metagenomic next-generation sequencing in ICU patients suspected monomicrobial and polymicrobial bloodstream infections.

Introduction: Early and effective application of antimicrobial medication has been evidenced to improve outcomes of patients with bloodstream infection (BSI). However, conventional microbiological tests (CMTs) have a number of limitations that hamper a rapid diagnosis. Methods: We retrospectively collected 162 cases suspected BSI from intensive care unit with blood metagenomics next-generation sequencing (mNGS) results, to comparatively evaluate the diagnostic performance and the clinical impact on antibiotics usage of mNGS. Results and discussion: Results showed that compared with blood culture, mNGS detected a greater number of pathogens, especially for Aspergillus spp, and yielded a significantly higher positive rate. With the final clinical diagnosis as the standard, the sensitivity of mNGS (excluding viruses) was 58.06%, significantly higher than that of blood culture (34.68%, P<0.001). Combing blood mNGS and culture results, the sensitivity improved to 72.58%. Forty-six patients had infected by mixed pathogens, among which Klebsiella pneumoniae and Acinetobacter baumannii contributed most. Compared to monomicrobial, cases with polymicrobial BSI exhibited dramatically higher level of SOFA, AST, hospitalized mortality and 90-day mortality (P<0.05). A total of 101 patients underwent antibiotics adjustment, among which 85 were adjusted according to microbiological results, including 45 cases based on the mNGS results (40 cases escalation and 5 cases de-escalation) and 32 cases on blood culture. Collectively, for patients suspected BSI in critical condition, mNGS results can provide valuable diagnostic information and contribute to the optimizing of antibiotic treatment. Combining conventional tests with mNGS may significantly improve the detection rate for pathogens and optimize antibiotic treatment in critically ill patients with BSI.

Effects of alkaline mineral complex supplementation on production performance, serum variables, and liver transcriptome in calves.

Calf diarrhea causes huge economic losses to livestock due to its high incidence and mortality rates. Alkaline mineral complex water is an alkaline solution containing silicon, sodium, potassium, zinc, and germanium, and has biological benefits and therapeutic effects. This study aimed to evaluate the impact of alkaline mineral complex water supplementation on the health of calves and to investigate the effect of Alkaline mineral complex water supplementation on neonatal calf serum variables and the liver transcriptome. Sixty Holstein calves (age 1.88 ± 0.85 days, weight 36.63 ± 3.34 kg) were selected and randomly divided into two groups: the T group (treatment group with alkaline mineral complex water supplemented during the experiment) and C group (control group without alkaline mineral complex water supplementation). Alkaline mineral complex water supplementation significantly increased the body weight for calves aged 60 d and average daily gain during the experimental period (1-60 d). In addition, Alkaline mineral complex water supplementation could significantly decrease the diarrhea rate for calves aged 16-30 d, enhance the T-AOC, IgG, IGF-1, and IGFBP-2 in concentrations. The results of KEGG enrichment analysis in transcriptomics indicate that Alkaline mineral complex water supplementation inhibited the target IL-1B gene of the NF-kappa B signaling pathway of liver. Alkaline mineral complex water supplementation decreased calf diarrhea and improved partial immune function, anti-inflammatory activity, antioxidant capacity, and health of calves. Alkaline mineral complex is a candidate to replace medicated feed additives. Alkaline mineral complex waterAlkaline mineral complex waterAlkaline mineral complex waterAlkaline mineral complex waterAlkaline mineral complex waterAlkaline mineral complex waterAlkaline mineral complex water.

Medium chain fatty acid supplementation improves animal metabolic and immune status during the transition period: A study on dairy cattle.

The transition period is the stage of the high incidence of metabolic and infectious diseases in dairy cows. Improving transition dairy cows' health is crucial for the industry. This study aimed to determine the effects of dietary supplementation medium-chain fatty acids (MCFAs) on immune function, metabolic status, performance of transition dairy cows. Twenty multiparous Holstein cows randomly assigned to two treatments at 35 d before calving. 1) CON (fed the basal 2) MCFA treatment (basal diet was supplemented at an additional 20 g MCFAs mixture every day) until 70 d after calving. The results showed that the serum amyloid A myeloperoxidase concentrations in the blood of cows in MCFA treatment significantly decreased during the early lactation (from 1 d to 28 d after calving) 0.03, 0.04, respectively) compared with the CON, while the tumor necrosis factor concentration was significantly decreased at 56 d after calving (P = 0.02). In addition, the concentration of insulin in the pre-calving (from 21 d before calving to calving) blood of cows in MCFA treatment was significantly decreased (P = 0.04), and concentration of triglyceride also showed a downward trend at 28 d after calving 0.07). Meanwhile, MCFAs supplementation significantly decreased the concentrations of lithocholic acid, hyodeoxycholic acid, and hyocholic acid in the blood at 1 d calving (P = 0.02, < 0.01, < 0.01, respectively), and the level of hyocholic acid taurocholic acid concentrations (P < 0.01, = 0.01, respectively) decreased dramatically at 14 d after calving. However, compared with the CON, the pre-calving dry matter intake and the early lactation milk yield in MCFA treatment were significantly decreased (P = 0.05, 0.02, respectively). In conclusion, MCFAs supplementation transition diet could improve the immune function and metabolic status of dairy cows, and the health of transition cows might be beneficial from the endocrine status.

Preoperative serum CA125 level and age at diagnosis: An effective prognosis prediction tool for patients with early-stage endometrial cancer.

OBJECTIVE: To investigate the combined predictive value of the preoperative serum cancer antigen 125 (CA125) level and age at diagnosis among patients with early-stage endometrial cancer (EC) after initial treatment. METHODS: We retrospectively analyzed data from patients with early-stage EC from 1999 to 2015 in multiple institutions in China. All 447 patients received postoperative adjuvant radiotherapy for FIGO 2009 stage I and II EC with complete data on preoperative serum CA125 levels. All patients were divided into four groups according to the ESMO-ESGO-ESTRO risk classification. The predictive probability of 5-year overall survival (OS) and the sensitivity and specificity of CA125 and age were calculated. RESULTS: The median follow-up time was 59 months (3-201 months). The 5-year OS and disease-free survival rates were 94.4% and 89.1%. Multivariate analysis showed that the preoperative CA125 level and age at diagnosis were independent prognostic factors for 5-year OS. The area under the curve for CA125 combined with age at diagnosis for 5-year OS was .692, and the corresponding sensitivity and specificity were 68.2% and 68.2% (p < .002), which were significantly better than the corresponding values for CA125 or age alone. After all 447 patients were divided into four groups according to CA125 combined with age, the 5-year OS of the elderly and higher CA125 group was only 73.7%. CONCLUSIONS: Although preoperative CA125 had limited sensitivity in predicting the prognosis for early-stage EC after initial treatment, it remains a useful serum marker for risk assessment of early-stage EC. Combining CA125 with age may increase its predictive sensitivity.

Producing natural functional and low-carbon milk by regulating the diet of the cattle-The fatty acid associated rumen fermentation, biohydrogenation, and microorganism response.

Conjugated linoleic acid (CLA) has drawn significant attention in the last two decades for its various potent beneficial effects on human health, such as anticarcinogenic and antidiabetic properties. CLA could be generally found in ruminant products, such as milk. The amount of CLA in ruminant products mainly depends on the diet of the animals. In general, the fat content in the ruminant diet is low, and dietary fat supplementation can be provided to improve rumen activity and the fatty acid (FA) profile of meat and milk. Especially, dietary 18-carbon polyunsaturated FA (C18 PUFA), the dominant fat source for ruminants, can modify the milk FA profile and other components by regulating the ruminal microbial ecosystem. In particular, it can improve the CLA in milk, intensify the competition for metabolic hydrogen for propionate producing pathways and decrease methane formation in the rumen. Therefore, lipid supplementation appears to be a promising strategy to naturally increase the additional nutritional value of milk and contribute to lower methane emissions. Meanwhile, it is equally important to reveal the effects of dietary fat supplementation on rumen fermentation, biohydrogenation (BH) process, feed digestion, and microorganisms. Moreover, several bacterial species and strains have been considered to be affected by C18 PUFA or being involved in the process of lipolysis, BH, CLA, or methane emissions. However, no review so far has thoroughly summarized the effects of C18 PUFA supplementation on milk CLA concentration and methane emission from dairy cows and meanwhile taken into consideration the processes such as the microorganisms, digestibility, rumen fermentation, and BH of dairy cattle. Therefore, this review aims to provide an overview of existing knowledge of how dietary fat affects rumen microbiota and several metabolic processes, such as fermentation and BH, and therefore contributes to functional and low-carbon milk production.

Effects of Concentrate Levels in Prepartum Diet on Milk Performance, Energy Balance and Rumen Fermentation of Transition Montbéliarde-Holstein Crossbred Cows.

This study was conducted to investigate the effect of three rates of prepartum dietary concentrate feeding on the milk performance, energy balance, and rumen fermentation of Montbéliarde−Holstein crossbred cows. Eighteen transition Montbéliarde−Holstein crossbred cows with similar days of gestation (258 ± 12 day) and body weights (622 ± 44 kg) were selected and randomly divided into three groups. In the prepartum period, the addition of concentrates accounted for 0.3% (low concentrate, LC), 0.6% (medium concentrate, MC), and 0.9% (high concentrate, HC) of the cow's body weight. The forage was corn stover, which was fed to the cows ad libitum with free access to water. Postpartum, all of the cows were fed a common lactation total mixed ration. The experimental period lasted from 21 days prepartum to 28 days postpartum. The energy balance (EB), net energy intake (NEI), and dry matter intake (DMI) of the HC group were greater than those of the other groups (p < 0.05). Likewise, the non-esterified fatty acids (NEFA), ß-hydroxybutyric acid (BHBA), and total bilirubin (TBIL) in the blood of the LC group had significantly higher concentrations than they did in the other groups (p < 0.05). Moreover, the increase in the level of dietary concentrate had no significant effect on the rumen fermentation parameters (p > 0.05), and the total intestinal digestibility of dry matter (DM), crude protein (CP), and ether extract (EE) in the HC group was significantly higher (p < 0.05) than it was in the other groups during the prepartum period. In conclusion, the administration of the MC diet in the prepartum period had no negative effect on the performance and rumen fermentation of postpartum dairy cows and can satisfy the energy needs of prepartum dairy cows. Therefore, under our experimental conditions, the 0.6% prenatal concentrate feeding amount was the most appropriate for Montbéliarde−Holstein crossbred cows.

The Blood Immune Cell Count, Immunoglobulin, Inflammatory Factor, and Milk Trace Element in Transition Cows and Calves Were Altered by Increasing the Dietary n-3 or n-6 Polyunsaturated Fatty Acid Levels.

Transition dairy cows experience sudden changes in both metabolic and immune functions, which lead to many diseases in postpartum cows. Therefore, it is crucial to monitor and guarantee the nutritional and healthy status of transition cows. The objective of this study was to determine the effect of diet enriched in n-3 or n-6 polyunsaturated fatty acid (PUFA) on colostrum composition and blood immune index of multiparous Holstein cows and neonatal calves during the transition period. Forty-five multiparous Holstein dairy cows at 240 days of pregnancy were randomly assigned to receive 1 of 3 isoenergetic and isoprotein diets: 1) CON, hydrogenated fatty acid (control), 1% of hydrogenated fatty acid [diet dry matter (DM) basis] during prepartum and postpartum, respectively; 2) HN3, 3.5% of extruding flaxseed (diet DM basis, n-3 PUFA source); 3) HN6, 8% of extruding soybeans (diet DM basis, C18:2n-6 PUFA source). Diets containing n-3 and n-6 PUFA sources decreased colostrum immunoglobulin G (IgG) concentration but did not significantly change the colostrum IgG yield compared with those with CON. The commercial milk yield (from 14 to 28 days after calving) was higher in the HN3 and HN6 than that in the CON. Furthermore, the n-3 PUFA source increased neutrophil cell counts in blood during the prepartum period and increased neutrophil percentage during the postpartum period when compared with those with control treatment. Diets containing supplemental n-3 PUFA decreased the serum concentration of interleukin (IL)-1ß in maternal cows compared with those in control and n-6 PUFA during prepartum and postpartum. In addition, the neonatal calf serum concentration of tumor necrosis factor (TNF) was decreased in HN3 compared with that in the HN6 treatment. The diet with the n-3 PUFA source could potentially increase the capacity of neutrophils to defend against pathogens in maternal cows by increasing the neutrophil numbers and percentage during the transition period. Meanwhile, the diet with n-3 PUFA source could decrease the pro-inflammatary cytokine IL-1ß of maternal cows during the transition period and decline the content of pro-inflammatary cytokine TNF of neonatal calves. It suggested that the highest milk production in n-3 PUFA treatment may partially be due to these beneficial alterations.