A novel prognostic model based on epithelial-mesenchymal transition-related genes predicts patient survival in gastric cancer.

BACKGROUND: Gastric cancer (GC) represents a major malignancy and is the third deathliest cancer globally. Several lines of evidence indicate that the epithelial-mesenchymal transition (EMT) has a critical function in the development of gastric cancer. Although plentiful molecular biomarkers have been identified, a precise risk model is still necessary to help doctors determine patient prognosis in GC. METHODS: Gene expression data and clinical information for GC were acquired from The Cancer Genome Atlas (TCGA) database and 200 EMT-related genes (ERGs) from the Molecular Signatures Database (MSigDB). Then, ERGs correlated with patient prognosis in GC were assessed by univariable and multivariable Cox regression analyses. Next, a risk score formula was established for evaluating patient outcome in GC and validated by survival and ROC curves. In addition, Kaplan-Meier curves were generated to assess the associations of the clinicopathological data with prognosis. And a cohort from the Gene Expression Omnibus (GEO) database was used for validation. RESULTS: Six EMT-related genes, including CDH6, COL5A2, ITGAV, MATN3, PLOD2, and POSTN, were identified. Based on the risk model, GC patients were assigned to the high- and low-risk groups. The results revealed that the model had good performance in predicting patient prognosis in GC. CONCLUSIONS: We constructed a prognosis risk model for GC. Then, we verified the performance of the model, which may help doctors predict patient prognosis.

Endometrial cancer with a POLE mutation progresses frequently through the type I pathway despite its high-grade endometrioid morphology: a cohort study at a single institution in Japan.

POLE-mutated endometrial cancer (EC) frequently shows high-grade endometrioid histology, which represents heterogeneity in the dualistic classification of EC. This study aimed to assess the clinicopathology and pathogenesis of POLE-mutated EC due to the scarcity of related information for Asian women. POLE variants were sequenced in tissues of Japanese women with EC. The tumor mutation burden (TMB) was assessed in tissues with a POLE variant of unknown significance. In the POLE-mutated EC tissues, the immunostaining expression of CD8, hormonal receptors, and p53 was evaluated, and the POLE variants in cancer and atypical endometrial hyperplasia (AEH) lesions were assessed by laser-capture microdissection. POLE variants were identified in five patients (3.9%) with high-grade endometrioid carcinoma among 127 patients with EC (S459F in two tissues and P441P in three tissues with a high TMB). The five cancer tissues coexisted with normal endometrium and/or AEH. Both AEH and cancer cells showed hormonal receptor positivity and harbored the same POLE mutation. Two patients showed a subclonal overexpression pattern of p53 in cancer and AEH lesions. In conclusion, POLE-mutated EC progresses through the type I pathway, even though it frequently shows high-grade endometrioid morphology. The common POLE mutation sites in EC might vary among races.

Role of the tumour necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) axis in autoimmune thyroid disease.

BACKGROUND: TNF-like weak inducer of apoptosis (TWEAK), its receptor fibroblast growth factor-inducible 14 (Fn14) and its scavenger receptor CD163 (sCD163) have known associations with many autoimmune diseases. However, the role of the TWEAK axis in autoimmune thyroid disease (AITD) remains unclear. Therefore, the aim of this study was to investigate the role of the TWEAK-Fn14 axis in the pathogenesis of AITD. METHODS: Serum levels of soluble TWEAK (sTWEAK) and sCD163 were measured in 38 patients with Graves' disease (GD), 40 patients with Hashimoto's thyroiditis (HT) and 40 healthy controls (HCs). Additionally, the mRNA expression of TWEAK and Fn14 in peripheral blood mononuclear cells (PBMCs) was explored, and the protein expression of TWEAK and Fn14 in thyroid glands surgically removed from 10 patients with GD, 10 patients with HT and 10 HCs was studied by immunohistochemical staining. RESULTS: The results showed that the serum levels of sTWEAK were significantly reduced in patients with HT and inversely correlated with antithyroid peroxidase antibody (TPOAb) levels. Additionally, high levels of sCD163 and a high sCD163/sTWEAK ratio were positively associated with the TPOAb levels in patients with HT and the thyrotropin receptor antibody (TRAb) levels in patients with GD. TWEAK mRNA expression and protein expression were upregulated in thyroid glands and PBMCs from patients with HT. CONCLUSION: Expression of the TWEAK-Fn14 axis was upregulated in patients with AITD and might play a role in the pathogenesis of AITD.

Gestation-specific changes in maternal thyroglobulin during pregnancy and lactation in an iodine-sufficient region in China: a longitudinal study.

OBJECTIVES: To describe the changes in thyroglobulin (Tg) based upon gestational and postpartum concentrations in healthy pregnant women from an iodine-sufficient region in China, and to evaluate the use of Tg as a biomarker for iodine-sufficient pregnant women. DESIGN: A longitudinal study of Tg change in normal pregnant women from an iodine-sufficient region. PATIENTS AND MEASUREMENTS: Blood and urine samples were obtained from 133 pregnant women. Urinary iodine concentration (UIC) was measured using an ammonium persulfate method. Serum iodine concentration was required by inductively coupled plasma mass spectrometry (ICP-MS). Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), total triiodothyronine (TT3), antithyroid peroxidase antibody (TPOAb), antithyroglobulin antibody (TgAb) and Tg were measured using an electrochemiluminescence immunoassay. RESULTS: Thyroglobulin concentrations were higher in early pregnancy (pregnancy at 8 weeks vs nonpregnancy: 11·42 ng/ml vs 8·8 ng/ml, P < 0·01) and maintained a stable level, and then increased greatly at the 36th week. After delivery, Tg decreased to nonpregnant levels. During pregnancy, maternal Tg was not correlated with thyroid function, UIC or urine iodine-creatinine ratio (UI/Cr). Cord blood Tg was much higher compared to maternal Tg levels at the 36w (57·34 vs 14·86 ng/ml, P < 0·001) and correlated positively with cord FT4 (r = 0·256, P < 0·05), cord TT4 (r = 0·263, P < 0·05) and maternal UI/Cr at 36w (r = -0·214, P < 0·05). CONCLUSIONS: Our work demonstrates that Tg is elevated during pregnancy, and the effect of pregnancy should be taken into consideration when Tg is used as a biomarker for the iodine status. Cord blood Tg is much higher than maternal Tg levels at the 36w and is correlated with maternal iodine status.

Expression of SIP1 is strongly correlated with LDHA and shows a significantly poor outcome in gastric cancer.

Smad interacting protein 1 (SIP1) plays an important role in the epithelial-mesenchymal transition (EMT) process by downregulating E-cadherin. Lactate dehydrogenase A (LDHA) is a crucial enzyme that plays an important role in the final step of the Warburg effect by converting pyruvate to lactate irreversibly. EMT and Warburg effect are the hallmarks of advanced gastric cancer progression. Recently, EMT has been thought to be implicated in cancer metabolism. In this study, we want to find whether there was a correlation between the expressions of SIP1 and LDHA in gastric cancer and whether expression of SIP1 alone or in combination with LDHA is associated with the progression of gastric cancer. In the present study, we examined SIP1 and LDHA expression by immunohistochemistry analysis on tissue microarray (TMA) containing tumor tissues and matched non-neoplastic mucosa (NNM). Prognostic value and correlation with other clinicopathologic factors were evaluated. In this study, we investigated the expression of SIP1 and LDHA in 261 cancer tissues and their matched NNM using tissue microarray. The immunohistochemistry analysis showed that the expression of SIP1 and LDHA was significantly higher in cancer tissues than in NNM (P = 0.002 P = 0.000, respectively). The expression of SIP1was significantly associated with age, Lauren grade, and histologic differentiation (P < 0.05). The expression of SIP1 was strongly correlated with LDHA expression in gastric cancer (P = 0.000, R = 0.589). The combined expression of SIP1 and LDHA was significantly associated with age, Lauren grade, and histologic differentiation (P < 0.05). Survival analysis demonstrated that the expression of SIP1 or LDHA was associated with significantly shorter overall survival (OS) (P = 0.003, P = 0.000, respectively) and disease-free survival (DFS) (P = 0.003, P = 0.000, respectively). The combined expression of SIP1 and LDHA was associated with less survival time in gastric cancer patients (P = 0.000). The multivariate analysis showed that the expressions of SIP1 and LDHA in gastric cancer (GC) were independent prognostic factors for OS (hazard ratio = 1.465, 95 %CI 1.128-1.901, P = 0.004, hazard ratio = 1.514, 95 %CI 1.091-2.101 P = 0.013, respectively) and DFS (hazard ratio = 1.461, 95 %CI 1.130-1.890, P = 0.004, hazard ratio = 1.550 95 %CL1.119-2.147 P = 0.008, respectively). Our study indicated that expressions of SIP1 and LDHA are independent prognostic factors in gastric cancer patients and may be predictive of poor outcomes.

Upregulated protein arginine methyltransferase 1 by IL-4 increases eotaxin-1 expression in airway epithelial cells and participates in antigen-induced pulmonary inflammation in rats.

Protein arginine methyltransferases (PRMTs), catalyzing methylation of both histones and other cellular proteins, have emerged as key regulators of various cellular processes. This study aimed to identify key PRMTs involved in Ag-induced pulmonary inflammation (AIPI), a rat model for asthma, and to explore the role of PRMT1 in the IL-4-induced eosinophil infiltration process. E3 rats were i.p. sensitized with OVA/alum and intranasally challenged with OVA to induce AIPI. The expressions of PRMT1-6, eotaxin-1, and CCR3 in lungs were screened by real-time quantitative PCR. Arginine methyltransferase inhibitor 1 (AMI-1, a pan-PRMT inhibitor) and small interfering RNA-PRMT1 were used to interrupt the function of PRMT1 in A549 cells. In addition, AMI-1 was administrated intranasally to AIPI rats to observe the effects on inflammatory parameters. The results showed that PRMT1 expression was mainly expressed in bronchus and alveolus epithelium and significantly upregulated in lungs from AIPI rats. The inhibition of PRMTs by AMI-1 and the knockdown of PRMT1 expression were able to downregulate the expressions of eotaxin-1 and CCR3 with the IL-4 stimulation in the epithelial cells. Furthermore, AMI-1 administration to AIPI rats can also ameliorate pulmonary inflammation, reduce IL-4 production and humoral immune response, and abrogate eosinophil infiltration into the lungs. In summary, PRMT1 expression is upregulated in AIPI rat lungs and can be stimulated by IL-4. Intervention of PRMT1 activity can abrogate IL-4-dependent eotaxin-1 production to influence the pulmonary inflammation with eosinophil infiltration. The findings may provide experimental evidence that PRMT1 plays an important role in asthma pathogenesis.

Preparation of red jujube powder with high content of Amadori compounds and higher antioxidant activity by controlling the Maillard reaction.

Amadori compounds (ACs) are stable compounds produced in the early stage of the Maillard reaction (MR) with health benefits such as immunomodulatory, antithrombosis, and tumor-preventive effects. Jujube is a medicinal and edible fruit in China. It is rich in free amino acids and reducing sugar, but traditionally, little attention was paid to the formation of ACs when jujube was processed, neither the influence of ACs on health effects. In this paper, we aimed to increase ACs through controlling the MR during different heating processes of jujube powder with adjusted water content and find the most effective AC that contributed to the antioxidant effects of jujube powder. The optimal dry-heating conditions to produce ACs were as follows: The water activity was 0.294, the heating temperature was 90°C, and the time was 120 min. After processing, the ACs content of jujube powder was 18.55 ± 0.19 mg/g dry weight (DW), which was more than 100 times of those in the unheated jujube powder (0.153 ± 0.003 mg/g DW). Besides, the antioxidant activity of jujube powder after dry-heating process was higher than that of unheated one. As the most abundant AC in the dry-heated jujube powder (12.90 ± 0.75 mg/g DW), N-(1-deoxy-d-fructose-1-yl) proline (Fru-Pro) showed the highest antioxidant activity (62% of equivalent l-ascorbic acid) among 12 ACs in ferric reducing antioxidant power assay. This result provided a method to produce jujube product with high content of ACs and confirmed the positive contribution of Fru-Pro to the antioxidant activity of the jujube powder.

Cinnamaldehyde: An effective component of Cinnamomum cassia inhibiting Helicobacter pylori.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum cassia Presl (Cinnamomum cassia) is a common traditional Chinese medicine, which can promote the secretion and digestion of gastric juice, improve the function of gastrointestinal tract. Cinnamaldehyde (CA) is a synthetic food flavoring in the Chinese Pharmacopoeia. AIM OF THE STUDY: This study aimed to search for the active ingredient (CA) of inhibiting H. pylori from Cinnamomum cassia, and elucidate mechanism of action, so as to provide the experimental basis for the treatment of H. pylori infection with Cinnamomum cassia. MATERIALS AND METHODS: It's in vitro and in vivo pharmacological properties were evaluated based on minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and an acute gastric inflammation model in mice infected with H. pylori. Drug safety was evaluated using the CCK8 method and high-dose administration in mice. The advantageous characteristics of CA in inhibiting H. pylori were confirmed using acidic conditions and in combination with the antibiotics. The mechanism underlying the action of CA on H. pylori was explored using scanning electron microscopy (SEM), adhesion experiments, biofilm inhibition tests, ATP and ROS release experiments, and drug affinity responsive target stability (DARTS) screening of target proteins. The protein function and target genes were verified by molecular docking and Real-Time quantitative reverse transcription PCR (qRT-PCR). RESULTS: The results demonstrated that CA was found to be the main active ingredient against H. pylori in Cinnamomum cassia in-vitro tests, with a MIC of 8-16 µg/mL. Moreover, CA effectively inhibited both sensitive and resistant H. pylori strains. The dual therapy of PPI + CA exhibited remarkable in vivo efficacy in the acute gastritis mouse model, superior to the standard triple therapy. DARTS, molecular docking, and qRT-PCR results suggested that the target sites of action were closely associated with GyrA, GyrB, AtpA, and TopA, which made DNA replication and transcription impossible, then leading to inhibition of bacterial adhesion and colonization, suppression of biofilm formation, and inhibition ATP and enhancing ROS. CONCLUSIONS: This study demonstrated the suitability of CA as a promising lead drug against H. pylori, The main mechanisms can target GyrA ect, leading to reduce ATP and produce ROS, which induces the apoptosis of bacterial.

A Chinese survey of clinical practice on the management of thyroid eye disease.

Objective: The management of thyroid eye disease (TED) has undergone significant changes for decades. The study sought to investigate current clinical practice on the management of TED in China. Methods: An online questionnaire survey was conducted from April to May 2023. The questionnaire involved diagnostic criteria for TED, multidisciplinary treatment (MDT) collaboration, and treatment preference for mild, moderate, and severe TED. Results: A total of 289 questionnaires were collected, with 165 from endocrinologists and 124 from ophthalmologists. Only 36.7% of participants claimed there was an MDT clinical pattern for TED in their institutions. The coverage of biological agents was around 10% or lower. These were distinctly lower than in Western countries. About 62.6% of participants believed the incidence of TED has increased in recent years. Imaging techniques were used widely to assist in the diagnosis of TED. However, there was still controversy regarding the definition of proptosis in the Chinese population. Most doctors managed risk factors and provided orbital supportive treatments of artificial tears and glasses. For mild active TED, endocrinologists (39.4%) were inclined to recommend therapy for hyperthyroidism alone, while ophthalmologists (43.6%) preferred orbital corticosteroid injections. Currently, the most widely used treatment for moderate to severe active TED was high-dose intravenous corticosteroid (94.8%), while orbital radiotherapy combined with immunosuppressive agents was the most recognized second-line therapy (43.6%). Conclusion: The study documented the consistency and differences between current clinical practices in the management of TED in China and the recently updated guidelines. There was a remarkable difference between ophthalmology and endocrinology departments, warranting management optimization.

Isobavachalcone: A redox antifungal agent impairs the mitochondria protein of Cryptococcus neoformans.

Isobavachalcone (IBC) is a natural small molecule with various biological activities; however, its inhibitory effects on Cryptococcus neoformans remain unclear. In our study, IBC showed a good antifungal effect. Through in vitro experiments, its minimum inhibitory concentration was 0.5-1 µg/mL. It exhibited the same antifungal effect as Amphotericin B in brain and lung infections in in vivo experiments. IBC also showed a synergistic antifungal effect with emodin with lower toxicity, and C. neoformans did not develop drug resistance to IBC. In the mechanistic study, significantly damaged mitochondria of C. neoformans, a significant reduction in mitochondrial membrane potential and adenosine triphosphate production, and an increase in hydrogen peroxide (H2O2) caused by IBC were observed using transmission electron microscopy. Through drug affinity-responsive target stability combined with phenotype detection, riboflavin synthases of aconitase and succinate dehydrogenase were screened. Molecular docking, quantitative polymerase chain reaction experiments, target inhibitor and agonist intervention, molecular interaction measurements, and minimum inhibitory concentration detection of the constructed expression strains revealed that IBC targeted the activity of these two enzymes, interfered by the tricarboxylic acid cycle, inhibited the production of adenosine triphosphate, blocked electron transport, reduced mitochondrial membrane potential, and induced antioxidation imbalance and reactive oxygen species accumulation, thus producing an antifungal effect. Therefore, IBC is a promising lead drug and redox antifungal agent for C. neoformans.

Nanoengineered Red Blood Cells Loaded with TMPRSS2 and Cathepsin L Inhibitors Block SARS-CoV-2 Pseudovirus Entry into Lung ACE2+ Cells.

The enzymatic activities of Furin, Transmembrane serine proteinase 2 (TMPRSS2), Cathepsin L (CTSL), and Angiotensin-converting enzyme 2 (ACE2) receptor binding are necessary for the entry of coronaviruses into host cells. Precise inhibition of these key proteases in ACE2+ lung cells during a viral infection cycle shall prevent viral Spike (S) protein activation and its fusion with a host cell membrane, consequently averting virus entry to the cells. In this study, dual-drug-combined (TMPRSS2 inhibitor Camostat and CTSL inhibitor E-64d) nanocarriers (NCs) are constructed conjugated with an anti-human ACE2 (hACE2) antibody and employ Red Blood Cell (RBC)-hitchhiking, termed "Nanoengineered RBCs," for targeting lung cells. The significant therapeutic efficacy of the dual-drug-loaded nanoengineered RBCs in pseudovirus-infected K18-hACE2 transgenic mice is reported. Notably, the modular nanoengineered RBCs (anti-receptor antibody+NCs+RBCs) precisely target key proteases of host cells in the lungs to block the entry of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), regardless of virus variations. These findings are anticipated to benefit the development of a series of novel and safe host-cell-protecting antiviral therapies.

Wilson disease complicated by Crohn disease: A case report and literature review.

RATIONAL: Wilson disease (WD), also known as hepatolenticular degeneration, is an autosomal-recessive hereditary disease with abnormal copper metabolism. Crohn disease (CD) is a chronic inflammatory gastrointestinal disease, which belongs to inflammatory bowel disease, all segments of the gastrointestinal tract can be affected, especially the terminal ileum and colon, accompanied by extraintestinal manifestations and related immune disorders. WD complicated by ulcerative colitis has been reported before, but WD complicated by CD has not been reported so far. PATIENT CONCERNS AND DIAGNOSIS: We presented the first report of a young patient with WD complicated by CD, who was admitted to the hospital because of repeated low fever, elevated C-reactive protein for 3 years, and anal fistula for 6 months. INTERVENTIONS AND OUTCOMES: In this complicated disease, Ustekinumab is safe and effective. LESSONS: We conclude that copper metabolism and oxidative stress play important roles in WD and CD.

Identification and validation of an epithelial-mesenchymal transition-related lncRNA pairs prognostic model for gastric cancer.

Background: Gastric cancer (GC) is a common malignancy. A mounting body of evidence has demonstrated the correlation between GC prognosis and epithelial-mesenchymal transition (EMT)-related biomarkers. This research constructed an available model using EMT-related long noncoding RNA (lncRNA) pairs to predict the survival for GC patients. Methods: The transcriptome data along with clinical information on GC samples were derived from The Cancer Genome Atlas (TCGA). Differentially expressed EMT-related lncRNAs were acquired and paired. Univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were applied to filter lncRNA pairs, and the risk model was built to investigate its effect on the prognosis of GC patients. Then, the areas under the receiver operating characteristic curves (AUCs) were calculated and the cutoff point for distinguishing low- or high-risk GC patients was identified. And the predictive ability of this model was tested in the GSE62254. Furthermore, the model was evaluated from the perspectives of survival time, clinicopathological parameters, infiltration of immunocytes, and functional enrichment analysis. Results: The risk model was built by using the identified twenty EMT-related lncRNA pairs, and it was not necessary to know the specific expression level of each lncRNA. Survival analysis pointed out that GC patients with high risk had poorer outcomes. Additionally, this model could be an independent prognostic variable for GC patients. The accuracy of the model was also verified in the testing set. Conclusions: The new predictive model constructed here is composed of EMT-related lncRNA pairs, with reliable prognostic values, and can be utilized to predict the survival of GC.

Laponite Lights Calcium Flickers by Reprogramming Lysosomes to Steer DC Migration for An Effective Antiviral CD8+ T-Cell Response.

Immunotherapy using dendritic cell (DC)-based vaccination is an established approach for treating cancer and infectious diseases; however, its efficacy is limited. Therefore, targeting the restricted migratory capacity of the DCs may enhance their therapeutic efficacy. In this study, the effect of laponite (Lap) on DCs, which can be internalized into lysosomes and induce cytoskeletal reorganization via the lysosomal reprogramming-calcium flicker axis, is evaluated, and it is found that Lap dramatically improves the in vivo homing ability of these DCs to lymphoid tissues. In addition, Lap improves antigen cross-presentation by DCs and increases DC-T-cell synapse formation, resulting in enhanced antigen-specific CD8+ T-cell activation. Furthermore, a Lap-modified cocktail (Lap@cytokine cocktail [C-C]) is constructed based on the gold standard, C-C, as an adjuvant for DC vaccines. Lap@C-C-adjuvanted DCs initiated a robust cytotoxic T-cell immune response against hepatitis B infection, resulting in > 99.6% clearance of viral DNA and successful hepatitis B surface antigen seroconversion. These findings highlight the potential value of Lap as a DC vaccine adjuvant that can regulate DC homing, and provide a basis for the development of effective DC vaccines.

Gestational and Postpartum Complications in Patients with First Trimester Thyrotoxicosis: A Prospective Multicenter Cohort Study from Northeast China.

Objective: Gestational transient thyrotoxicosis (GTT) and Graves' disease (GD) are the most common causes of hyperthyroidism during pregnancy. However, few studies have compared pregnancy outcomes of patients who had GTT with those who had GD in the first trimester of pregnancy. Methods: We conducted a prospective multicenter cohort study in China. Participants received questionnaires, physical examinations, and underwent measurements of thyrotropin (TSH), free thyroxine (fT4), thyroid peroxidase antibody (TPOAb), TSH receptor antibody (TRAb), and urinary iodine in the first trimester. The patients diagnosed with either GTT or GD and normal thyroid function (NTF) group were followed until delivery. The thyroid function and pregnancy outcomes were reported. Results: A total of 125 pregnant women with thyrotoxicosis and 246 age-matched pregnant women with NTF were included. (1) The thyroid function of the GTT group returned to normal range in the third trimester, but was consistently abnormal in the GD group. (2) The incidence of gestational diabetes mellitus (GDM) in the GTT group (11.5%, 9/78) was significantly higher than that in NTF group (4.9%, 12/246) (p = 0.037). The incidence of premature delivery in the GD untreated (30.8%, 8/26, p = 0.002) and treated groups (28.6%, 6/21, p = 0.008) was both, respectively, higher than that in the NTF group (7.7%, 19/246). Miscarriage (15.4%, 4/26 vs. 3.7%, 9/246, p = 0.026) and gestational hypertension (19.2%, 5/26 vs. 3.3%, 8/246, p = 0.004) were more prevalent in the GD untreated group than in the NTF group. (3) The presence of positive TRAb and positive TPOAb in the first trimester were independent risk factors for miscarriage (odds ratio [OR] = 5.23, confidence interval [CI] = 1.11-24.78, p = 0.037) and low birth weight infants (OR = 7.76, CI = 1.23-48.86, p = 0.029), respectively. Conclusion: In conclusion, pregnancy outcomes appear variable, according to the etiology of first trimester thyrotoxicosis. GTT appears to be associated with GDM. GD appears to be associated with an increased risk of premature delivery, gestational hypertension, and miscarriage. The diagnosis of GTT and GD patients during early pregnancy and appropriate treatment of GD patients may be associated with improved pregnancy outcomes.

Brushite-coated Mg-Nd-Zn-Zr alloy promotes the osteogenesis of vertebral laminae through IGF2/PI3K/AKT signaling pathway.

Biodegradable magnesium (Mg) alloys have been extensively investigated in orthopedic implants due to their suitable mechanical strength and high biocompatibility. However, no studies have reported whether Mg alloys can be used to repair lamina defects, and the biological mechanisms regulating osteogenesis are not fully understood. The present study developed a lamina reconstruction device using our patented biodegradable Mg-Nd-Zn-Zr alloy (JDBM), and brushite (CaHPO4·2H2O, Dicalcium phosphate dihydrate, DCPD) coating was developed on the implant. Through in vitro and in vivo experiments, we evaluated the degradation behavior and biocompatibility of DCPD-JDBM. In addition, we explored the potential molecular mechanisms by which it regulates osteogenesis. In vitro, ion release and cytotoxicity tests revealed that DCPD-JDBM had better corrosion resistance and biocompatibility. We found that DCPD-JDBM extracts could promote MC3T3-E1 osteogenic differentiation via the IGF2/PI3K/AKT pathway. The lamina reconstruction device was implanted on a rat lumbar lamina defect model. Radiographic and histological analysis showed that DCPD-JDBM accelerated the repair of rat lamina defects and exhibited lower degradation rate compared to uncoated JDBM. Immunohistochemical and qRT-PCR results showed that DCPD-JDBM promoted osteogenesis in rat laminae via IGF2/PI3K/AKT pathway. This study shows that DCPD-JDBM is a promising biodegradable Mg-based material with great potential for clinical applications.

Usefulness of serum thyrotropin for risk prediction of differentiated thyroid cancers does not apply to microcarcinomas: results of 1,870 Chinese patients with thyroid nodules.

The objectives of this study were to investigate whether preoperative serum thyrotropin (TSH) concentrations can be used for risk prediction of differentiated thyroid cancers (DTC), in particular, microcarcinomas (DTMC), which may be in an early stage of development of DTC. The cohort of this retrospective study consisted of 1,870 patients who underwent surgery on thyroid nodules at a single hospital in an iodine-sufficient region in China. Serum TSH and anti-thyroid antibodies were measured and diagnoses were based on surgical pathology reports. Of 1,870 patients, 14.4% (n=269) had DTC. Eighty-nine DTCs were DTMC. As TSH increased, the prevalence of DTC rose clearly. The odds ratio in favor of having DTC with a serum TSH 1.9-4.8 mIU/L and > 4.8 mIU/L, compared with having a serum TSH 1.0-1.9 mIU/L were 1.57 (95% CI 1.03-2.40, P=0.038) and 5.71 (95% CI 2.31-14.14, P=0.0002), respectively. A similar pattern was yielded when excluding subjects with high thyroid autoantibodies. Higher TSH was also associated with lymph node metastasis and advanced disease (stage III and IV). However, preoperative TSH was 1.17 mIU/L in patients with DTMC vs. 1.08 mIU/L in patients with benign pathology (P = 0.80). The pattern of escalating prevalence with higher TSH did not apply to DTMC. In conclusion, serum TSH is not a good risk predictor of DTMCs. Elevated TSH level may be related to advanced stage, that is, progression of thyroid cancer, but not with the development of thyroid cancer, since microcarcinomas do not have any relation with TSH level.

Formation of Amadori compounds in LIGAO (concentrated pear juice) processing and the effects of Fru-Asp on cough relief and lung moisturization in mice.

LIGAO (concentrated pear juice) has been used for more than 1000 years to treat respiratory complaints such as cough and expectoration in China, but the study of the mechanism of its antitussive effects and ability to moisten the lungs is limited. This study found that the content of Amadori compounds (ACs) and other nutrients changed during LIGAO processing. Furthermore, N-(1-deoxy-D-fructos-1-yl)-aspartic acid (Fru-Asp), the most abundant and characteristic AC in LIGAO, was prepared and studied. The antitussive test revealed that Fru-Asp could significantly reduce the frequency of cough and prolong the cough latent period in mice. A high dose of Fru-Asp (250 mg kg-1) in mice provided better therapeutic activities than that of dextromethorphan hydrobromide tablets (30 mg kg-1). In the Fru-Asp pretreated group, Fru-Asp significantly alleviated inflammation in LPS-induced acute lung injury mice. Fru-Asp can significantly decrease the levels of TNF-α and IL-ß in mice by 11%. Additionally, Fru-Asp exhibited angiotensin-converting enzyme (ACE) inhibitor activity (IC50 = 0.242 mM). The contribution and health benefits of Fru-Asp on cough relief were first reported in this study, which also substantiated it as a functional component of LIGAO. The results provided the basis for future research on the health effects of ACs and a method to improve the added value of LIGAO and other pear products.