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.

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.

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.

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.

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.

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.

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.

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.

Recent developments in PD-1/PD-L1 blockade research for gastroesophageal malignancies.

Gastroesophageal cancers (GECs) comprise malignancies in the stomach, esophagus, and gastroesophageal junction. Despite ongoing improvements in chemoradiotherapy, the clinical outcomes of GEC have not significantly improved over the years, and treatment remains challenging. Immune checkpoint inhibitors (ICIs) have been the subject of clinical trials worldwide for several years. Encouraging results have been reported in different countries, but further research is required to apply ICIs in the clinical care of patients with GEC. This review summarizes completed and ongoing clinical trials with programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway blockers in GEC and current biomarkers used for predicting PD-1/PD-L1 blockade efficacy. This review captures the main findings of PD-1/PD-L1 antibodies combined with chemotherapy as an effective first-line treatment and a monotherapy in second-line or more treatment and in maintenance therapy. This review aims to provide insight that will help guide future research and clinical trials, thereby improving the outcomes of patients with GEC.

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.

Fecal Microbiota Transplantation Effectively Cures a Patient With Severe Bleeding Immune Checkpoint Inhibitor-Associated Colitis and a Short Review.

Immune checkpoint inhibitors (ICIs) have opened up a new way for tumor therapy but simultaneously led to the occurrence of immune-related adverse events. We report a case of successful treatment of PD-1 inhibitor-associated colitis with fecal microbiota transplantation (FMT). The patient was a palatal malignant melanoma who developed diarrhea and hematochezia accompanied by fever, gastrointestinal bleeding, and infection after the third treatment with PD-1 (Toripalimab). The patient received general treatment unsuccessful, corticosteroid therapy after initial success but rapid loss of response, and finally successful treatment after fecal microbiota transplantation.

Outcomes of Early-Pregnancy Antithyroid Drug Withdrawal in Graves' Disease: A Preliminary Prospective Follow-Up Study.

Objective: The use of antithyroid drugs (ATDs) carries potential risk for teratogenic effects. For women with well-controlled hyperthyroidism on a low dose of ATDs, drug withdrawal upon pregnancy is recommended by international medical guidelines. Therefore, it is necessary to determine the characteristics of patients suitable for ATD withdrawal, subsequent changes in thyroid function after ATD discontinuation, and its impact on pregnancy and offspring outcomes. Methods: This prospective study recruited 63 pregnant women with well-controlled Graves' hyperthyroidism who had stopped ATDs during early pregnancy. Patients were followed up until the end of pregnancy and data on pregnancy outcomes were collected. Results: Overall, 20 patients (31.7%) had rebound of hyperthyroidism. Patients with either subnormal thyrotropin (TSH) levels (TSH <0.35 mIU/L, odds ratio [OR] = 5.12, confidence interval [CI = 1.29-20.34], p = 0.03) or positive thyrotropin receptor antibody (TRAb) (TRAb >1.75 IU/L, OR = 3.79, [CI = 1.17-12.30], p = 0.02) at the time of ATDs withdrawal presented a higher risk of rebound than those with either normal TSH levels or negative TRAb. Patients with both subnormal TSH and positive TRAb at the time of ATD withdrawal were more likely to experience rebound (83.3%, 5/6) than those with both normal TSH and negative TRAb (13%, 3/23, OR = 33.33, [CI = 2.83-392.60], p = 0.003). The prevalence of adverse pregnancy outcomes was significantly higher in patients who experienced rebound compared with those who did not (55.0% vs. 9.3%, OR = 11.92, [CI = 3.08-46.18], p = 0.0002). Conclusions: Subnormal TSH levels and TRAb positivity at the time of ATD withdrawal in early pregnancy may be associated with rebound of Graves' hyperthyroidism. Rebound of hyperthyroidism during pregnancy may increase the risk of adverse pregnancy outcomes. Larger prospective studies are needed to confirm these findings.

A Family with Liddle Syndrome Caused by a Novel Stop-Gain Mutation in the γ Subunit of Epithelial Sodium Channels.

Liddle syndrome (OMIM #177200) is an autosomal dominant disorder caused by gain-of-function pathogenic variants in the genes encoding epithelial sodium channel subunits, including α (SCNN1A), ß (SCNN1B), and γ (SCNN1G). The majority of the reported cases carry SCNN1B variants (∼90%), and SCNN1A/G variants are relatively infrequent. Here, we report a 24-year-old Chinese male patient diagnosed with early-onset hypertension. Laboratory tests revealed hypokalemia with a low level of plasma renin activity. Liddle syndrome was confirmed by high-throughput sequencing, which identified a novel nonsense variant Q591X in the SCNN1G gene, resulting in the PY motif's deletion. The patient's father has the same mutation, and his mother and sister are normal. All eleven variants in the SCNN1G gene were summarized. Liddle syndrome usually presents with early onset of hypertension with hypokalemia and low-renin activity, but it can be clinically heterogeneous. It is necessary to utilize next-generation sequencing to clarify the diagnosis to identify Liddle syndrome in young patients with hypertension and to perform early treatment and prevent a series of adverse outcomes caused by hypertension.

Ultrasensitive flower-like TiO2/Ag substrate for SERS detection of pigments and melamine.

TiO2 flower like nanomaterials (FLNMs) are fabricated via a hydrothermal method and Ag nanoparticles (NPs) are deposited via electron beam evaporation. Several biological pigments (CV, R6G and RhB) are selected as target molecules to investigate their surface enhanced Raman scattering (SERS) property. The results demonstrate ultrasensitivity and high reproducibility. They reveal that the limit of detection (LOD) is 4.17 × 10-16 M and the enhancement factor (EF) is 2.87 × 1010 for CV, and the LOD is 5.01 × 10-16 M and 7.94 × 10-14 M for R6G and RhB, respectively. To assess the reproducibility on TiO2/Ag FLNMs SERS substrates, they are tested with 1.0 × 10-13 M of CV, 1.0 × 10-13 M of R6G and 1.0 × 10-11 M of RhB, respectively. The relative standard deviations (RSD) are less than 12.93%, 13.52% and 11.74% for CV, R6G and RhB, respectively. In addition, we carry out melamine detection and the LOD is up to 7.41 × 10-10 M, which is over 1000 times lower than the severest standards in the world. Therefore, the obtained TiO2 FLNMs have potential application in detecting illegal food additives.

Mesenchymal stem cells inhibited the apoptosis of alveolar epithelial cells caused by ARDS through CXCL12/CXCR4 axis.

Mesenchymal stem cells (MSCs) have a wide range of anti-inflammatory and immunomodulatory effects and have been observed to have potential therapeutic potential in the clinical treatment of various diseases. We pretreated lung cancer cells A549 with tumor necrosis factor (TNF-α), knocked down the key chemokine receptor CXCR4 on MSCs using lentivirus, and induced acute respiratory distress syndrome (ARDS) mouse model using lipopolysaccharide (LPS) and CXCL12 expression in vivo by adeno-associated virus (AAV-rh10) infection in mice. By co-culturing the MSCs with A549 and in vivo experiments, we observed the effects of MSCs on cell biological functions after inflammatory stimulation, oxidative stress, and the amelioration of lung injury in ARDS mice. TNF-α inhibited A549 proliferation and promoted apoptosis, scorch death-related factor activity, and oxidative stress factor were increased and CXCL12 levels in the cell supernatant were decreased. The co-culture of MSCs was able to increase cell activity and decrease oxidative stress factor levels, and this effect was not present after the knockdown of CXCR4 in MSCs. In vivo transplantation of MSCs significantly attenuated lung injury in ARDS, inhibited serum pro-inflammatory factors in mice, and down-regulated expression of apoptotic and focal factors in lung tissues while blocking CXCR4 or CXCL12 lost the repairing effect of MSCs on ARDS lung tissues. After the co-culture of MSC and lung cancer cells, the expression of CXCR4 on the surface of lung cancer cells was significantly increased, and more CXCR4 and CXCL12 acted together to activate more pro-survival pathways and inhibit apoptosis induced by TNF-α.

CdS Micrometer Hollow Spheres for Detecting Alcohols Except Methanol with Strong Anti-interference Ability.

Cadmium sulfide micrometer hollow spheres (CdS MHs) were fabricated by a hydrothermal method. The performance of the CdS MHs sensor was evaluated by detecting volatile organic compounds such as methanol, ethanol, 1-propanol, isopropanol, n-butanol, iso-butyl alcohol, iso-amyl alcohol, acetone, and xylene. It was found that the optimum working temperature of the CdS MHs sensor is 190 °C. The response of the CdS MHs can reach 27.4-100 ppm ethanol and reach 84.55-100 ppm isopropanol. Comparing the response to pure 5 ppm isopropanol (iso-amyl alcohol) with the mixture of 5 ppm isopropanol (iso-amyl alcohol) and 50 ppm acetone or 5 ppm isopropanol (iso-amyl alcohol) and 50 ppm methanol, the relative deviation was -1.33% (-7.11%) or -6.19% (9.20%). It suggested that the CdS MHs sensor had a strong anti-interference ability to methanol and acetone and is suitable for detecting alcohols except methanol. Therefore, the CdS MHs sensor had good response and is a promising alcohol detection material.

A Chinese survey on clinical practice in hyperthyroidism management: comparison with recent studies and guidelines.

OBJECTIVE: To conduct a questionnaire survey of the current clinical practice for overt hyperthyroidism in China. METHODS: An online questionnaire survey was conducted in July 2020. The two questionnaires covered 35 and 8 questions about non-pregnancy and pregnancy clinical practice for overt hyperthyroidism, respectively. RESULTS: One thousand, two hundred fifty-six physicians participated. Chief physicians and associate chief physicians accounted for 58.6% of the participants. Approximately 95.2% of the respondents chose the thyrotropin receptor antibody (TRAb) test to clarify the etiology of thyrotoxicosis, while only 27.0% of them chose radioactive iodine uptake (RAIU). In terms of treatment for non-pregnant patients, anti-thyroid drugs (ATDs) were the first choice, and most of the clinicians chose methimazole. Compared with clinicians in recent studies, Chinese physicians used serum TRAb to diagnose Graves' disease more commonly, and there were obviously more physicians preferring ATDs. For maternal hyperthyroidism, most physicians preferred propylthiouracil administration before or during the first trimester, which is consistent with the 2016 American Thyroid Association (ATA) guidelines. In terms of the initial ATD dose, monitoring the treatment process, indications for ATD withdrawal and treatment of special cases, the preferences of Chinese physicians were generally consistent with the guidelines. CONCLUSION: Chinese physicians can generally follow the ATA guidelines for the diagnosis and treatment of hyperthyroidism. Moreover, there are small differences from foreign studies or the guidelines with respect to particular problems. These findings provide evidence for future clinical research in China.

Large-Sized Graphene Oxide Nanosheets Increase DC-T-Cell Synaptic Contact and the Efficacy of DC Vaccines against SARS-CoV-2.

Dendritic cell (DC) vaccines are used for cancer and infectious diseases, albeit with limited efficacy. Modulating the formation of DC-T-cell synapses may greatly increase their efficacy. The effects of graphene oxide (GO) nanosheets on DCs and DC-T-cell synapse formation are evaluated. In particular, size-dependent interactions are observed between GO nanosheets and DCs. GOs with diameters of >1 µm (L-GOs) demonstrate strong adherence to the DC surface, inducing cytoskeletal reorganization via the RhoA-ROCK-MLC pathway, while relatively small GOs (≈500 nm) are predominantly internalized by DCs. Furthermore, L-GO treatment enhances DC-T-cell synapse formation via cytoskeleton-dependent membrane positioning of integrin ICAM-1. L-GO acts as a "nanozipper," facilitating the aggregation of DC-T-cell clusters to produce a stable microenvironment for T cell activation. Importantly, L-GO-adjuvanted DCs promote robust cytotoxic T cell immune responses against SARS-CoV-2 spike 1, leading to >99.7% viral RNA clearance in mice infected with a clinically isolated SARS-CoV-2 strain. These findings highlight the potential value of nanomaterials as DC vaccine adjuvants for modulating DC-T-cell synapse formation and provide a basis for the development of effective COVID-19 vaccines.

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.