Endometrial microbial dysbiosis and metabolic alteration promote the development of endometrial cancer.

OBJECTIVE: Emerging evidence suggests that the endometrial microbiome plays important roles in the development of endometrial cancer (EC). Here, we evaluate stage-specific roles of microbial dysbiosis and metabolic disorders in patients with EC, patients with endometrial hyperplasia (EH), and patients afflicted with benign uterine conditions (CK). METHODS: This prospective cohort study included 33 women with EC, 15 women with endometrial EH, and 15 women with benign uterine conditions (CK) from November 2022 to September 2023. Different typical endometrial samples were imaged with a scanning electron microscope and a transmission electron microscope. The endometrial microbiome was assessed by sequencing the V3-V4 region of the 16S rRNA gene and the ITS1 to fill the gap in relation to the study of the uterine fungal microbiome. Moreover, liquid chromatography-mass spectrometry-based metabolomics was used to identify and quantify metabolic changes among these groups. RESULTS: The endometrial microbiome revealed that there is a structural microbiome shift and an increase in the α-diversity in the EC and EH cases, distinguishable from the benign cases, especially the fungal community structure. The fungal microbiome from patients with EC and EH was altered relative to controls and dominated by Penicillium sp. By contrast, Sarocladium was more abundant in controls. Significant differences were observed in the composition and content of compounds between benign cases and EC, especially estradiol-like metabolism-related substances. Altered microbiota was correlated with the concentrations of interleukin-6 (IL-6), IL-11, transforming growth factor-beta, and ß-glucuronidase activity especially the relative abundance increase of Penicillium sp. CONCLUSIONS: This study suggested that the endometrial microbiome is complicit in modulating the development of EC such as estrogen activity and a pro-inflammatory response. Our work provides a new insight into the endometrial microbiome from a perspective of stages, which opens up new avenues for EC prognosis and therapy.

Identifying optimal ranges of weight gain at the end of the second trimester result from a population-based cohort study.

OBJECTIVE: To identify the optimal weight gain at the end of the second trimester. DESIGN: This was a population-based cohort study from the antenatal care system in Tianjin, China. We calculated gestational weight gain (GWG) based on the weight measured in the first trimester and the end of the second trimester. Restricted cubic spline analysis was performed to model the possible non-linear relationships between GWG and adverse outcomes. The optimal GWG was defined as the value of the lowest risk. Non-inferiority margins and the shape of the spline curves identified the recommended ranges in Chinese-specific BMI categories. SETTING: Tianjin Maternal and Child Health Cohort. PARTICIPANTS: Singleton pregnant women aged 18-45 years. RESULTS: In total, 69 859 pregnant women were included. Adverse outcome (including stillbirth, preterm birth, hypertensive disorders of pregnancy, gestational diabetes mellitus, small and large for gestational age) was significantly associated with GWG at the end of the second trimester. The risk score was non-linearly correlated with GWG in the underweight, normal weight and overweight groups. GWG at the end of the second trimester should not be < 7 kg in underweight group. For most normal-weight women, a GWG of about 8 kg is optimal. Pregnant women who are overweight should not have a GWG of more than 9 kg. We advised women with overweight and obesity to keep positive growth of GWG (> 0 kg) in the first and second trimesters. CONCLUSIONS: According to the comprehensive adverse maternal and infant outcomes, we recommend the optimal GWG at the end of the second trimester. This study may provide a considerable reference for weight management.

Clinical manifestations and prognosis of unexpected uterine sarcoma of uterine fibroids in Tianjin China.

BACKGROUND: Uterine sarcoma is a rare malignancy of women and fewer uterine sarcomas are detected preoperatively. The reported incidence of preoperatively diagnosed uterine sarcoma (PDUS) was 0.07%. This study aims to identify the prevalence of unexpected uterine sarcoma (UUS) after operation for presumed leiomyoma and compare clinical outcomes after primary therapy. METHODS: A retrospective study was performed evaluating all uterine sarcoma diagnosed in Tianjin Central Hospital of Gynecology and Obstetrics between May 2011 and July 2016.We used the χ2 and T tests to assess the incidence and clinical features of patients. The Kaplan-Meier method was used to calculate disease-related survival. RESULTS: The study retrospectively analyzed 6625 patients with uterine fibroids and found 45 UUS patients and 21 patients of PDUS. The incidence of UUS is (45/6625) 0.67%. The incidence of UUS in patients undergoing total hysterectomy was higher undergoing tumor resection (P < 0.001); the age of UUS is younger than PDUS (P = 0.046); the differences in menopausal status and primary complaints between the two groups are not statistically significant. The PDUS group had more patients with Stage II and III sarcomas than the UUS group (P < 0.001); the duration of symptoms in the PDUS group was longer than in the UUS group (P = 0.033). The 5-year overall survival (OS) rate of the UUS group (77.7%) is higher than the PDUS group (46.3%) (P < 0.001). CONCLUSIONS: The incidence of UUS is low. UUS has a younger age of onset, shorter history of the disease, earlier clinical stage, and better prognosis.

Gut microbiota composition influences outcomes of skeletal muscle nutritional intervention via blended protein supplementation in posttransplant patients with hematological malignancies.

BACKGROUND: Skeletal muscle atrophy is an important and independent predictor of survival after hematopoietic stem cell transplantation (HSCT). Our previous study found that soy-whey blended protein (SWP) can improve muscle mass in acute leukemia patients. OBJECTIVE: We aimed to explore potential factors that influence muscle outcomes after nutritional intervention. METHODS: In this case-control study, 13 patients who received HSCT and failed to improve muscle function within half a year were included. After two months of SWP intervention, the subjects were divided into two groups (MSI: muscle status improved; MNI: muscle status not improved). 16S rDNA sequencing, principal coordinate analysis (PCoA) and the PICRUSt algorithm were used to analyze the composition, structure and function of the intestinal microbiota between the groups. This study was registered in the Chinese Clinical Trial Registry (ChiCTR 1800017765). RESULTS: SWP significantly improved muscle status (muscle area: from 330.4 mm2 to 384.8 mm2, p = 0.02; muscle strength: from 19.2 kg to 21.3 kg, p = 0.04). However, there were a small number of subjects whose muscle status was not effectively improved. After SWP intervention, the diversity (Shannon: from 1.7 to 3.8, p = 0.01; Simpson: from 0.6 to 0.8, p = 0.015) of the intestinal microbiota in the MSI group increased significantly, whereas that in the MNI group did not. Principal component analysis (PCA) revealed separate groupings of the microbiota of the Baseline-MSI and Endpoint-MSI time points in the MSI group. Opposite patterns of microbial abundance change were found between the MSI group (75% of changed genera were increased) and the MNI group (80% of changed genera were decreased). Three bacterial taxa (negative correlation: Streptococcus; positive correlations: Ruminococcus and Veillonella) were significantly related to muscle improvement outcomes. Both pentose phosphate (p = 0.048) and amino acid biosynthesis (p = 0.039), which are related to muscle metabolism, were found to be significantly changed in the MSI group through PICRUSt algorithm prediction. CONCLUSIONS: Our results suggest that the intestinal microbiota plays important roles in the regulation of muscle metabolism.

China's food loss and waste embodies increasing environmental impacts.

Food loss and waste (FLW) hampers global food security, human health and environmental sustainability. However, monitoring and benchmarking FLW reduction is often constrained by the lack of reliable and consistent data, especially for emerging economies. Here we use 6 yr large-scale field surveys and literature data to quantify the FLW of major agrifood products along the entire farm-to-fork chain in China. We show that 27% of food annually produced for human consumption in the country (349 ± 4 Mt) is lost or wasted; 45% of this is associated with postharvest handling and storage and 13% with out-of-home consumption activities. We also show that the land, water, carbon, nitrogen and phosphorus footprints associated with total FLW are similar to those of a medium-sized country (such as the United Kingdom's in the case of carbon footprint). These results highlight the importance of better primary data to inform FLW reduction actions and ensure food security and sustainability.

Understanding the role of milk in regulating human homeostasis in the context of the COVID-19 global pandemic.

Although data from clinical observation have directly shown that children aged 0-14 years are less susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than those who are between 15 and 64 years old, due to a lack of biological evidence of differences in cell entry receptors between age groups, it remains debatable whether children are actually less susceptible than adults. To date, studies on COVID-19 have consistently shown that pediatric patients generally have relatively milder cytokine release syndrome and lower mortality rates than adults. Interestingly, similar phenomena of relatively mild symptoms in children have been observed in previous outbreaks of coronaviruses, including SARS-CoV and MERS-CoV. In fact, in the early stage of life, there are many mechanisms that spontaneously regulate excessive inflammatory responses. Milk, as the main food of infants, not only provides necessary energy and nutrients but also plays an important role in regulating homeostasis related to the immune system, gut microecology and nutrition balance. This review discusses some roles of milk in regulating human homeostasis, especially in the disease states. These clues provide new insight and references for personal care at home and/or in the hospital during the global COVID-19 pandemic.

Role of the pretreatment neutrophil-to-lymphocyte ratio in the survival of primary parotid cancer patients.

BACKGROUND: To analyze the value of the pretreatment neutrophil-to-lymphocyte ratio (NLR) in the survival of patients with parotid cancer. METHODS: In total, 249 patients were enrolled. Information including age, sex, pretreatment NLR, and pathologic variables such as, tumor stage, intraparotid node (IPN) metastasis, and follow-up findings was extracted and analyzed. RESULTS: IPN metastasis was noted in 45 (18.1%) patients, and the mean NLR was 2.48, with a range from 1.5 to 6.1. The NLR was significantly associated with tumor stage, disease stage, and disease grade. A total of 73 patients died of the disease, and the 10 -year disease-specific survival (DSS) rate was 62%. In patients with an NLR<2.48, the 10 -year DSS rate was 68%; in patients with an NLR≥2.48, the 10 -year DSS rate was 58%, and the difference was significant (P=0.006). Cox model analysis showed that the NLR was an independent prognostic factor for DSS. CONCLUSION: The long-term survival of primary parotid cancer patients is relatively favorable, and the pretreatment NLR is significantly associated with prognosis.

Significance of intraparotid node metastasis in predicting local control in primary parotid cancer.

OBJECTIVE: To analyze the metastasis rate in intraglandular lymph nodes (IGLNs) with a focus on discussing the significance of IGLN metastasis in local control (LC) of parotid gland cancer (PGC). METHODS: A total of 337 patients were enrolled. Information including age; sex; and pathologic variables such as tumor (T) stage, IGLN metastasis, and follow-up findings was extracted and analyzed. RESULTS: IGLN metastasis was noted in 111 (32.9%) patients. Tumor stage, pathologic nodal stage, perineural invasion, resection status, and lymphovascular invasion were significantly related to IGLN metastasis. Local recurrence was noted in 67 (19.9%) patients. IGLN metastasis was an independent predictor of LC. The 10-year LC rate was 94% for patients without IGLN metastasis, 56% for patients with metastasis in no more than two IGLNs, and 22% for patients with metastasis in more than two IGLNs. This difference was significant (P < 0.001). CONCLUSION: The IGLN metastasis rate is relatively high in PGC patients and is significantly associated with disease grade and T stage. IGLN metastasis is associated with poorer local LC, and patients with more than two metastatic nodes have the worst prognosis. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:2309-2312, 2019.

The impact of changes in dietary knowledge on adult overweight and obesity in China.

Overweight and obesity are rapidly growing threats in China. Improvement in dietary knowledge can potentially prevent overweight and obesity, conditions which are receiving substantial attention from international organizations and governments. The purpose of this study was to investigate the impact of changes in dietary knowledge on adult overweight and obesity, using a balanced panel data consisting of 10,401 samples from the 2006, 2009, and 2011 iterations of the China Health and Nutrition Survey. Results indicate that overweight and obesity are becoming increasingly problematic in China, and the level of dietary knowledge among Chinese adults needs improvement. Moreover, the empirical results indicate that changes in dietary knowledge among adults has no significant influence on adult overweight and obesity, a likely result of lacking systematic dietary knowledge and having inadequate guidance on overweight/obesity-related behaviors.

A fibrinolytic protease AfeE from Streptomyces sp. CC5, with potent thrombolytic activity in a mouse model.

Fibrinolytic proteases have potential applications in cardiovascular disease therapy. A novel fibrinolytic protease, AfeE, with strong thrombolytic activity was purified from Streptomyces sp. CC5. AfeE displayed maximum activity at 40°C in the pH range of 7.0-12.0. It was strongly inhibited by serine protease inhibitor phenylmethanesulfonylfluoride, soybean trypsin inhibitor, tosyl-l-lysine chloromethyl ketone and tosyl-l-phenylalanine chloromethyl ketone. The activity of the enzyme was partially inhibited by Cu(2+), Co(2+) and Zn(2+). AfeE exhibited higher substrate specificity for fibrin than fibrinogen, which has rarely been reported in fibrinolytic enzymes. AfeE also showed high thrombolytic activity in a carrageenan-induced mouse tail thrombosis model. AfeE prolonged prothrombin time, activated partial thromboplastin time, and thrombin time in rat blood. A bleeding time assay revealed that AfeE did not prolong bleeding time in mice at a dose of 1mg/kg. No acute cytotoxicity was observed for AfeE at 320µg/well in human umbilical vein endothelial cells. The afeE gene was cloned from the genome of Streptomyces sp. CC5. Full-length AFE-CC5E contained 434 amino acids and was processed into a mature form consisting 284 amino acids by posttranslational modification, as revealed by high-resolution mass spectrometry analysis. These results indicate that AfeE is a prospective candidate for antithrombotic drug development.

Purification and Biochemical Characterization of a Novel Fibrinolytic Enzyme from Streptomyces sp. P3.

A novel proteolytic enzyme with fibrinolytic activity, FSP3, was purified from the recently isolated Streptomyces sp. P3, which is a novel bacterial strain isolated from soil. FSP3 was purified to electrophoretic homogeneity by ammonium sulfate precipitation, anion exchange, and gel filtration. FSP3 is considered to be a single peptide chain with a molecular mass of 44 kDa. The maximum activity of the enzyme was observed at 50°C and pH 6.5, and the enzyme was stable between pH 6 and 8 and below 40°C. In a fibrin plate assay, FSP3 showed more potent fibrinolytic activity than urokinase, which is a clinical thrombolytic agent acting as a plasminogen activitor. The activity was strongly inhibited by the serine protease inhibitor PMSF, indicating that it is a serine protease. Additionally, metal ions showed different effects on the activity. It was significantly suppressed by Mg(2+) and Ca(2+) and completely inhibited by Cu(2+), but slightly enhanced by Fe(2+). According to LC-MS/MS results, its partial amino acid sequences are significantly dissimilar from those of previously reported fibrinolytic enzymes. The sequence of a DNA fragment encoding FSP3 contained an open reading frame of 1287 base pairs encoding 428 amino acids. FSP3 is a bifunctional enzyme in nature. It hydrolyzes the fibrin directly and activates plasminogen, which may reduce the occurrence of side effects. These results suggest that FSP3 is a novel serine protease with potential applications in thrombolytic therapy.

[The effect of different fluoride concentrations on the expression of transforming growth factor-beta1 in ameloblast of rat incisor].

OBJECTIVE: To investigate the effect of different concentrations of fluoride on the expression of transforming growth factor-beta1 (TGF-beta1), and explore the mechanism of dental fluorosis. METHODS: 40 Wistar rats were randomly divided into three groups, and supplied with low dose F(-)(60 mgxL(-1), 13 rats), high dose F(-)(120 mgxL(-1), 13 rats) and distilled water(control group, 14 rats) respectively. After 10 weeks, hematoxylin-eosin (HE) and immunohistochemistry staining were used to observe the changes of the ameloblasts and the expression of TGF-beta1 in rat incisors. RESULTS: The fluoride groups showed typical symptoms of dental fluorosis. The surfaces of the rat teeth fed with fluoride appeared chalky color and cross striation on the enamel surface. The HE staining showed that the morphous of ameloblast were disarranged and cellular derangement, even appeared vacuolar change. TGF-beta1 were expressed both in ameloblast of the secretory and maturation stage, and also in stellate reticulum and stratum intermedium. The expression of TGF-beta1 in rat's ameloblasts in experiment group was significantly lower than that in the control group (P<0.01), yet low dose group and high dose group still had no significant difference (P>0.05). CONCLUSION: By inhibiting the expression of TGF-beta1 in ameloblast, fluoride interferes the normal signal transduction between epithelial and mesenchymal, and affect the differentiation and development of enamel, so leading to the occurrence of dental fluorosis.

[The effect of different concentrations of fluoride on the expression of Smad2/3 in ameloblast of rat incisor].

PURPOSE: To investigate the effect of different concentrations of fluoride on the expression of Smad2/3 which is a specific intracellular signal transduction molecule of TGF-ß, and to explore the mechanism of dental fluorosis in rat. METHODS: Forty Wistar rats were randomly divided into 3 groups.HE and immunohistochemistry were used to detect the changes of the ameloblasts and the expression of Smad2/3 in rat incisors. MetaMorph microscope images analysis system and SPSS12.0 software package were used to analyze the images and data. RESULTS: Typical symptoms of dental fluorosis were found in the fluoride group. The expression of Smad2/3 in the ameloblasts in the experimental group was significantly lower than that in the control group (P<0.01); but the difference was not significant between the low-dose group and high-dose group(P>0.05). CONCLUSIONS: By inhibiting the expression of Smad2/3 in ameloblasts, fluoride affects the differentiation and development of enamel,leading to the occurrence of dental fluorosis in rat.

[Effect of fluoride on the expression of MMP-20/TIMP-2 in ameloblast of rat incisor and the antagonistic effect of melatonin against fluorosis].

PURPOSE: To study the effect of concentration of fluoride on the expression of matrix metalloproteinase-20(MMP-20) and tissue inhibitors of metalloproteinase-2 (TIMP-2) in the ameloblast of rat incisor,and explore the formation mechanism of dental fluorosis. By comparing the different expression of MMP-20,TIMP-2 between fluoride group and the melatonin group,to decide whether melatonin has antagonitic effect on dental fluorosis. METHODS: Forty Wistar rats were randomly divided into 6 groups. The groups were as follows: control group,low-dose group, high-dose group,normal saline group and melatonin group. The animals were sacrificed 10 weeks after treatment. HE and immunohistochemical staining were used to observe the changes of ameloblasts and the expression of MMP-20 and TIMP-2 in rat incisors. MetaMorph microscope images analysis system was used to analyze the images, and SPSS12.0 software package was used for data analysis. RESULTS: The surface of rat incisors fed with fluoride had chalky color change and cross stritations could be seen on the enamel surface.In the fluoride group,the ameloblasts were disarranged, cells arranged in multi-layer,even showing vacuolar change.The changes in the high-dose group was severer than the low-dose group. MMP-20, TIMP-2 were expressed both in the secretory ameloblasts, and in the odontoblasts.The expression of MMP-20 in rat's ameloblasts in the experimental group was significantly lower than that in the control group (P < 0.01); and no significant difference was found between the low-dose and high-dose groups(P > 0.05). The difference of expression of TIMP-2 was not significant among all the groups. The difference of expression of MMP-20 and TIMP-2 was not significant between the melatonin and the fluoride groups. CONCLUSIONS: The excessive fluoride can inhibit the secretion of MMP-20 and disturb the balance between MMP-20 and TIMP-2,which lead to the delay of amelogenin removal and enamel demineralization. Melatonin has no antagonistic effect on the dental fluorosis. Supported by National Natural Science Foundation of China (30600509) and Natural Science Foundation of Liaoning Province (20102278).

Transplanted bone marrow stromal cells migrate, differentiate and improve motor function in rats with experimentally induced cerebral stroke.

Bone marrow stromal cells are multipotential cells that can be induced to differentiate into osteoblasts, chondrocytes, myocytes and adipocytes in different microenvironments. Recent studies revealed that bone marrow stromal cells could improve neurological deficits of various damages or diseases of the central nervous system such as Parkinson's disease, brain trauma, spinal cord injury and multiple sclerosis, and promote glia-axonal remodeling in animal brain subjected to an experimentally induced stroke. In the present study, bone marrow stromal cells were intracerebrally transplanted into the cerebrum following a transient middle cerebral artery occlusion. Our aim was to find out whether the bone marrow stromal cells could survive and express neural phenotypic proteins and, in addition, whether they could restore the behavioral and functional deficits of the cerebral ischemic rats. Our results demonstrated that transplanted bone marrow stromal cells survived and migrated to areas around the lesion site. Some of them exhibited marker proteins of astrocytes and oligodendrocytes. Bone marrow stromal cell implantation significantly reduced the transient middle cerebral artery occlusion-induced cortical loss and thinning of the white matter and enhanced cortical beta-III-tubulin immunoreactivity. Rats implanted with bone marrow stromal cells showed significant improvement in their performance of elevated body swing test and forelimb footprint analysis and only transient recovery of the adhesive-removal test. Our data support bone marrow stromal cells as a valuable source of autologous or allogenic donor cells for transplantation to improve the outcome following cerebral ischemia.