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OBJECTIVE Presenting treatment outcomes positively or negatively may differently influence treatment preferences and lead to sub-optimal decision in a medical context. This review systematically organised how positive versus negative framing of treatment outcomes influenced cancer treatment decisions of cancer patients and individuals without a cancer diagnosis. DESIGN Three databases (PubMed, PsycInfo and Scopus) were searched for studies reporting the effects of positive versus negative framing on cancer treatment decision-making from 1981 to December 2020. MAIN OUTCOME MEASURE The effects of positive versus negative framing on cancer treatment preferences and the elimination of framing effect were evaluated. RESULTS A total of 12 studies that met inclusion criteria were reviewed. Framing effect was consistently observed in individuals without a cancer diagnosis. There was not enough evidence to suggest a robust framing effect in cancer patients. Surgery was preferred in positive framing, whereas adjuvant therapy was preferred in negative framing. Justification intervention significantly eliminated framing effect. Mixed framing failed to eliminate framing effect. CONCLUSION Current recommendations for presenting treatment options are based on research in cancer-screening decision-making. Knowledge of how positive versus negative framing affect cancer patients' treatment decisions is still limited. Our review highlighted the need for continued research in this area.

Five dimeric Erythrina alkaloids, named erythrivarines J-N, were isolated from the barks of Erythrina variegata L. (Fabaceae). The erythrivarines J-L featured a 6/6/5/6/6/5/6/6/6 ring system and super conjugated double bond systems, causing intense color from blue to wine red, while erythrivarines M-N looked orange. The structures of the isolated compounds were elucidated by 1D and 2D NMR experiments combined with MS and confirmed by the X-ray crystal diffraction technique. The performed bioassay using HEI-OC-1 cells revealed neuroprotective properties of erythrivarine N against the hearing loss causing antibiotics, neomycin.

OBJECTIVE To determine the effects of changes in serum luteinizing hormone (LH) levels in the early stages of the gonadotropin-releasing hormone antagonist (GnRH-A) protocol on in vitro fertilization and embryo transfer/intracytoplasmic sperm injection clinical outcomes. METHODS Data from 2116 fresh embryo transfer cycles with the GnRH-A protocol were retrospectively analyzed. Patients were divided into two groups, ΔLH-increased and ΔLH-decreased, according to changes in serum LH levels on the day of GnRH-A addition compared with that on the start day of ovarian stimulation. Patients in whom ΔLH increased were categorized according to early-onset LH increases (serum LH level ≥10 mIU/mL or twice the baseline). RESULTS ΔLH increased and decreased in 14.9% and 85.1% of patients, respectively. The fertilization rate was lower, and fewer oocytes were retrieved in patients with increased ΔLH compared to those with decreased ΔLH (p .05). CONCLUSIONS Early increases in LH levels during GnRH-A protocol might affect the number of oocytes retrieved, but not the clinical outcomes.

Background This study aimed to explore the prognostic value of tumor mutational burden (TMB) combined with smoking status in advanced non‐small cell lung cancer (NSCLC) patients who received immune checkpoint inhibitor therapy (anti PD‐1/PD‐L1 therapy) combined with chemotherapy or anti‐angiogenesis therapy. Methods We conducted a retrospective analysis of NSCLC patients who underwent next‐generation sequencing test (either 295‐gene panel NGS or 1021‐gene panel NGS) from September 2017 to November 2020. The relationship between TMB and smoking status was investigated. Kaplan–Meier survival analysis was used to compare progression‐free survival (PFS) of the NSCLC patients who received combination immunotherapy grouped by TMB value and smoking status. Results We enrolled 323 cases and 388 cases of NSCLC patients in the 295‐gene panel cohort and 1021‐gene panel cohort, respectively. Positive correlation between TMB and smoking status was found in lung adenocarcinoma, but not in lung squamous cell carcinoma. Participants with both high TMB and smoking status who received immune checkpoint therapy combined with chemotherapy or anti‐angiogenesis therapy had longer PFS than other participants (p, The tumor mutational burden (TMB) value correlated with smoking status in lung adenocarcinoma patients, but not in lung squamous cell carcinoma patients in both NGS panels. The TMB value combined with smoking status might be used as a potential prognostic indicator for advanced non‐small cell lung cancer patients receiving immune checkpoint inhibitor combination therapy.

Objective: To analyze and evaluate the clinical efficacy of different treatment options for patients with peri-implant infection. Methods: The study period was from June 2019 to June 2020. Seventy-six patients with peri-implant infection that were treated in Stomatological Hospital of Hefei were selected as study samples. The patients were divided into a research group and a control group by random number table method in which the sample size of each group was n=38. Patients in the control group were treated with drugs combined with ultrasonic cleaning while patients in the research group were treated with guided bone regeneration combined with flap curettage. The indicators of the two groups were compared and analyzed. Results: The plaque index (PLI), probing depth (PD), and sulcus bleeding index (SBI) of the two groups after treatment were lower than those before treatment (P < 0.05). There was no significant difference between the groups (P > 0.05). However, the height of the implant marginal bone of the study group after treatment was higher than that of the control group (P < 0.05). Conclusion: The use of guided bone regeneration combined with flap curettage for patients with infection around dental implants promotes the fusion of bone and implants. The clinical effect was significant and this should be comprehensively promoted in medical institutions at all levels.

BACKGROUND Pseudogout is a benign joint lesion caused by the deposition of calcium pyro-phosphate dihydrate crystals, but it is invasive. Pseudogout of the temporo-mandibular joint (TMJ) is uncommon, and it rarely invades the skull base or penetrates into the middle cranial fossa. The disease has no characteristic clinical manifestations and is easily misdiagnosed. CASE SUMMARY We present two cases of tophaceous pseudogout of the TMJ invading the middle cranial fossa. A 46-year-old woman with a history of diabetes for more than 10 years was admitted to the hospital due to swelling and pain in the right temporal region. Another patient, a 52-year-old man with a mass in the left TMJ for 6 years, was admitted to the hospital. Maxillofacial imaging showed a calcified mass and severe bone destruction of the skull base in the TMJ area. Both patients underwent excision of the lesion. The lesion was pathologically diagnosed as tophaceous pseudogout. The symptoms in these patients were relieved after surgery. CONCLUSION Tophaceous pseudogout should be considered when there is a calcified mass in the TMJ with or without bone destruction. A pathological examination is the gold standard for diagnosing this disease. Surgical treatment is currently the recommended treatment, and the prognosis is good after surgery.

Nocardiosis is a rare, life-threatening, opportunistic, and suppurative infection. Its clinical manifestation lacks specificity, which makes early diagnosis difficult. A retrospective analysis of the clinical records of 11 patients with nocardiosis admitted to our hospital from January 2013 to November 2018 was conducted. All patients had at least one underlying disorder, such as an autoimmune disease (6/11), a blood malignancy (2/11), avascular necrosis of the femoral head (1/11), bronchiectasis (1/11), or pneumonia (1/11). The first-line treatment was trimethoprim–sulfamethoxazole (TMP–SMX); one or two additional antibiotics were given according to the drug-sensitive test. The median time from onset to treatment was 3 weeks (ranging from 1 to 9 weeks). The median duration of treatment after diagnosis was 20.5 weeks (ranging from 7 to 47 weeks). Eight patients were discharged and survived, and three patients died. This indicates that early use of TMP–SMX combined with sensitive antibiotics could improve the condition of patients and improve the cure rate (8/11). Clinically, it is necessary to consider the possibility of nocardiosis in patients with long-term use of immunosuppressants and poor response to treatment of common bacterial infections. Early diagnosis, timely treatment, and combination drug therapy are keys to improving the outcomes of patients with nocardiosis.

AIMS Laparoscopic surgery is widely used for diagnosing ovarian endometriosis but it has medical risks. This study explored the application of blood indicators in diagnosis and staging of ovarian endometriosis, aiming to develop a noninvasive diagnostic method. METHODS A total of 190 ovarian endometriosis patients were included in observation group, among these participants, 77 patients among them were stages I-II, and the rest 113 patients were stages III-IV, and a total of 103 healthy women as control group. Serum biochemical indexes, tumor markers, and cytokines levels in two groups were used for the diagnosis and staging of the disease. Area under the receiver operating characteristic (ROC) curve (AUC) predicted the value of individual and joint tests for indicators. RESULTS Biochemical indexes, namely, alkaline phosphatase (ALP), total protein (TP), and glucose (Glu) could distinguish patients from normal women; and that ALP and Glu could indicate disease staging. In tumor markers, alpha fetoprotein (AFP), carcinoembryonic antigen (CA) 125, CA199 and human epididymis protein 4 (HE4) helped to diagnose endometriosis; CA125, HE4, and cytokeratin 19 fragment (CYFRA21-1) could differentiate stages. In cytokines, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, interleukin (IL)-6, soluble fms-like tyrosine kinase receptor 1 (sflt-1), monocyte chemoattractant protein (MCP)-1 therefore, have values to diagnose endometriosis; VEGF, TNF-α, IL-6, and sflt-1 helped to differentiate disease staging. CONCLUSION Serological indicators in ovarian endometriosis patients were different from healthy women, which were of certain differential values in diagnosis and disease staging. The current study provided a novel strategy for endometriosis diagnosis.

Juniperus indica Bertol. is an herbal plant that belongs to the genus Juniperus, which is commonly used in traditional medicine to refresh the mind and for diuretic use. However, few studies have reported the function of J. indica Bertol. Hence, this study aimed to investigate the anti-tumor and synergistic potential of J. indica Bertol. extract (JIB extract) for melanoma cells. Our results indicated the anti-melanoma activity of JIB extract. JIB extract induced cell cycle arrest at the G0/G1 phase and decreased cyclin and cdk protein expressions. In addition, AKT/mTOR signaling and MAPK signaling were inhibited by JIB extract to suppress melanoma cell growth and proliferation. Additionally, JIB extract induced B16/F10 cell apoptosis via the caspase cascade. According to the JIB extract's anti-melanoma capacity, to assess the synergistic effects of cisplatin and JIB extract. The results demonstrated that JIB extract combined with cisplatin enhanced the inhibition of cell growth, proliferation, and survival through the obstruction of cell cycle progression and AKT/mTOR and MAPK signaling as well as the induction of cell apoptosis. Collectively, our results indicate that JIB extract showed anti-tumor effects and synergized with cisplatin against B16/F10 cells, indicating the possibility of JIB extract to be developed as adjuvant therapy for melanoma.

As a disease closely related to the metabolic syndrome, diabetes has become a public health issue that severely affects many people’s quality of life. The search for novel anti-diabetic agents remains the cornerstone to control this challenging disease. Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin and leptin signaling pathways, has turned out to be a potential target of type II diabetes mellitus (T2DM) and obesity. In recent years, the development of novel anti-diabetic drugs based on PTP1B inhibitors has captured the attention of many researchers. Thiazole, a five-membered heterocycle containing sulfur and nitrogen atoms, has been considered as an essential core skeleton for various active compounds. Furthermore, thiazolidines, representing a series of compounds with saturated thiazole rings, widely exist in natural products and synthetic compounds with a variety of pharmacological activities. Here, we focus on the emphasis of PTP1B in diabetes and the development of PTP1B inhibitors based on thiazole and thiazolidine derivatives in the past decade. Many PTP1B inhibitors and their chemical structures, selectivity, potency, and structure-activity relationship have been elaborated. The great majority of PTP1B inhibitors containing thiazole and thiazolidine moieties described in this review exhibit preferable activities, which would be of importance for the rational design and efficient application of PTP1B inhibitors with anti-diabetes activity.

Smarcd1 is a component of an evolutionary conserved chromatin remodeling complex—SWI/SNF, which is involved in transcription factor recruitment, DNA replication, recombination, and repair. Suppression of the SWI/SNF complex required for cellular differentiation and gene regulation may be inducible for cell proliferation and tumorigenicity. However, the inhibitory role of Smarcd1 in human glioblastoma cells has not been well illustrated. Both U87 and U251 human glioblastoma cell lines were employed in the present study. The lentivirus-mediated gene knockdown and overexpression approach was conducted to determine the function of Smarcd1. The protein levels were tested by western blot, and the relative mRNA contents were detected by quantitative real-time PCR. Cell viability was tested by CCK-8 and colony-forming assay. Transwell assays were utilized to evaluate the motility and invasive ability. Flow cytometry was employed to analyze cell cycle and apoptosis. SPSS software was used for statistical analysis. Low expression of Smarcd1 was observed in glioblastoma cell lines and in patients with high-grade glioma. Importantly, the depletion of Smarcd1 promoted cell proliferation, invasion, and chemoresistance, whereas enhanced expression of Smarcd1 inhibited tumor-malignant phenotypes. Mechanistic research demonstrated that overexpression of Smarcd1 decreased the expression of Notch1, while knockdown of Notch1 increased the expression of Smarcd1 through Hes1 suppression. Hence, the crosstalk between Smarcd1 and Notch1, which formed a feedback loop, was crucial in regulation of glioblastoma malignant phenotypes. Furthermore, targeting Smarcd1 could be a potential strategy for human glioblastoma treatment.

Background To determine the safety and efficacy of different doses of tolvaptan for treating Chinese cirrhotic patients with or without hyponatraemia who still had ascites after routine therapy with diuretics. Methods In the present placebo-controlled, randomized, double-blinded, multicentre clinical trial, patients with cirrhotic ascites who failed to adequately respond to a combination of an aldosterone antagonist plus an orally administered loop diuretic were randomly placed at a 4:2:1 ratio into 3 groups [the 15 mg/day tolvaptan group (N = 301), 7.5 mg/day tolvaptan group (N = 153) and placebo group (N = 76)] for 7 days of treatment. The effects and safety were evaluated on days 4 and 7. A change in body weight from baseline on day 7 of treatment was the primary endpoint. Results The administration of 7.5 or 15 mg/day tolvaptan significantly decreased body weight from baseline on day 7 of treatment compared to that with placebo treatment (P = 0.026; P = 0.001). For the secondary endpoints, changes in abdominal circumference from baseline and improvements in ascites were markedly different in the treatment groups and the placebo group on day 7 (P7.5 = 0.05, P15.0 = 0.002 and P7.5 = 0.037, P15.0 = 0.003), but there was no difference between the 7.5 mg/day and 15 mg/day dosage groups. The 24-h cumulative urine volume was higher in the 7.5 mg/day and 15 mg/day tolvaptan groups than the placebo group (P = 0.002, P P = 0.004). Sodium serum concentrations were higher in patients with hyponatraemia after tolvaptan treatment, with no significant difference between the two dosage groups. The incidence of serious adverse drug reactions was not different between the groups (P = 0.543). Conclusions Tolvaptan treatment at 7.5 mg per day might be a good therapeutic choice for Chinese cirrhotic patients with ascites who did not achieve satisfactory clinical responses to previous treatment regimens with combination therapy with an aldosterone antagonist and an orally administered loop diuretic. Trial registration NCT01349348. Retrospectively registered May 2011.

Oleanolic acid (OA, 3 β - hydroxyoleanolic acid-12-en-28-oic acid) is a pentacyclic triterpenoid present in many plants. As a new framework for development of semi synthetic triterpenoids, OA is of great significance in the discovery of anticancer drugs. Some of these derivatives, such as CDDO (2-cyano-3,12-dioxooleana-1, 9 (11)-dien-28-oic acid) have been verified in clinical trials, while other derivatives studied previously, such as SZC014, SZC015 and SZC017 (OA derivatives respectively), are also candidate drugs for cancer treatment. This paper reviews the preclinical studies, literature evidence, target analysis and anticancer mechanism of OA and its derivatives. The mechanism of action of its derivatives mainly includes anti-cancer cell proliferation, inducing tumor cell apoptosis, inducing autophagy, regulating cell cycle regulatory proteins, inhibiting vascular endothelial growth, anti angiogenesis, inhibiting tumor cell migration and invasion. In recent years, the molecular mechanism of OA and its derivatives has been elucidated. These effects seem to be mediated by the alterations in a variety of signaling pathways induced by OA and its derivatives. In conclusion, OA and its derivatives are considered as important candidate drugs for the treatment of cancer, indicating that OA and its derivatives have the potential to be used as anticancer drugs in practice.

Glioma is diagnosed as the most common intracranial malignant tumor. Cancer stem cells determine stemness and radioresistance, and may facilitate glioma recurrence. The present study aimed to investigate whether the long non-coding RNA (lncRNA) transmembrane phosphatase with tensin homology pseudogene 1 (TPTEP1) regulated cell stemness and radioresistance of glioma, and determine the underlying molecular mechanism of TPTEP1 in the modulation of glioma progression. Cell and molecular biology techniques were applied for investigating the role of TPTEP1 in glioma cell lines, animal model, and clinical samples. The results demonstrated that TPTEP1 attenuated stemness and radioresistance of glioma both in vitro and in vivo. In addition, TPTEP1 augmented MAPK14 expression by competitively interacting with microRNA (miR)-106a-5p, thus activating the P38 MAPK signaling pathway, and suppressing glioma stemness and radioresistance. TPTEP1 functionally bound to miR-106a-5p, which formed a reciprocal regulatory loop to stimulate the P38 MAPK signaling pathway. Low TPTEP1 expression levels were detected in high-grade glioma tissues compared with low-grade glioma tissues, and were positively associated with poor prognosis of patients with glioma. Furthermore, analysis using data from The Cancer Genome Atlas database confirmed the molecular mechanism and biological significance of dysregulation of TPTEP1 in glioma progression. Taken together, the results of the present study suggest that TPTEP1 may be applied as a diagnostic and prognostic indicator for glioma, and may be an alternative target for the treatment of glioma.

The single von Willebrand factor C-domain proteins (SVWCs) are mainly found in arthropods. Their expression may be regulated by several environmental stresses, including nutritional status and bacterial and viral infections. However, the underlying regulatory mechanism is unclear. In the present study, we identified a member of the SVWC family from the river prawn Macrobrachium nipponense as a soluble and bacteria-inducible pattern-recognition receptor (designated MnSVWC). In vitro, recombinant MnSVWC exhibited pronounced binding and Ca2+-dependent agglutinating abilities against diverse microbes, including Gram-negative bacteria (i.e. Escherichia coli and Aeromonas victoria), Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), and yeast (Pichia pastoris). ELISA assays revealed that recombinant MnSVWC recognizes a broad range of various pathogen-associated molecular patterns (PAMPs) and has high affinity to lipopolysaccharide and lysine-type and diaminopimelic acid-type peptidylglycan and d-galactose and low affinity to d-mannan and β-1,3-glucan. Mutant MnSVWCP57A with an impaired Glu-Pro-Asn (EPN) motif displayed reduced affinity to all these PAMPs to varying extent. Moreover, MnSVWC bound to the surface of hemocytes and promoted their phagocytic activity and clearance of invasive bacteria. RNAi-mediated MnSVWC knockdown in prawn reduced the ability to clear invading bacteria, but did not block the activities of the Toll pathway or the arthropod immune deficiency (IMD) pathway, or the expression of antimicrobial peptide genes. These results indicate that MnSVWC functions as an extracellular pattern-recognition receptor in M. nipponense that mediates cellular immune responses by recognizing PAMPs, agglutinating invasive microbes, and promoting phagocytosis in hemocytes.

Prior studies mainly focused on the effects of particulate air pollution on physiological health, relatively few researchers paid attention to psychological well-being. There is lacuna of knowledge on the effects of air pollution on aesthetic preferences. To fill this gap this study examines ten sample sites of urban green space, and eight photographs were taken on each site (seven photographs on the tenth site) in eight days, respectively. These photographs on a site contained the same scene. The aesthetic preference and perceived air quality of the photographs were evaluated by 766 participants, and wind speed, amount of clouds in the sky, particulate matter (PM2.5 and PM10) of each site were measured in situ when the photographs were taken. The results suggest that: (a) percentage of sky covered by cloud, PM2.5 and PM10 have significantly negative correlations with aesthetic preference and perceived air quality, while the regression analysis indicates that percentage of sky covered by cloud is the sole predictor for both aesthetic preference and perceived air quality; (b) perceived air quality is the reliable predictor of aesthetic preference. These findings contribute new knowledge to understand the particulate air pollution's effect on psychological well-being.

Anti-lipopolysaccharide factors (ALFs), as main host-defense molecules of crustaceans, form a unique family of antimicrobial peptides (AMPs). MnALF4 is one isoform of ALFs isolated from the freshwater prawn Macrobrachium nipponense. In the present study, MnALF4 gene was successfully expressed in the yeast Pichia pastoris and the recombinant MnALF4 protein exhibited efficient and broad-spectrum antimicrobial activities against both Gram-positive bacteria and Gram-negative bacteria in vitro. When prawns were injected with rMnALF4 before bacterial challenge with E. coli, the recombinant protein effectively promote the elimination of bacteria by the host. It manifested that rMnALF4 could effectively kill the invading bacteria in vivo. Treatment with rMnALF4 led to remarkable changes in bacterial morphology, such as spheroidization, oversized bacteria, and cell lysis. In addition, rMnALF4 showed weak hemolysis activity to the rabbit red blood cells. Our work suggests that MnALF4 plays an important role in Macrobrachium immunity and is worthy of further investigation as a potential antibacterial agent with high efficacy against bacterial infection and low toxicity to host cells.

Severe drug eruption (SDE), a common skin disease, becomes dangerous when it occurs in patients with human immunodeficiency virus (HIV). However, the molecular mechanisms are poorly understood. Forty patients including HIV+ SDE+ (n = 15), HIV- SDE+ (n = 15) and HIV+ SDE- (n = 10) subjects were enrolled in our study. All HIV+ patients were at acquired immune deficiency syndrome (AIDS) stage. Serum levels of TNF-α, IFN-γ, IL-4, IL-13, IL-6, CXCL9, and CCL17 were quantified by ELISA. Epstein-Barr virus (EBV) and cytomegalovirus (CMV) loads were quantified by RT-qPCR. CD4, CD8, Th1, Th2, TNF-α-CD8, and IFN-γ-CD8 T cell populations were measured by flow cytometry. Levels of biochemical indexes in HIV+ SDE+ patients were significantly different from in HIV- SDE+ patients (P < .05). EBV and CMV viral loads were significantly higher in HIV+ SDE+ patients, but not in HIV- SDE+ patients (P < .05). Inflammatory cytokines TNF-α and IFN-γ were significantly elevated in HIV+ SDE+ patients (P < .05). Th2/Th1 populations and TNF-α secreting or IFN-γ secreting CD8+ T cells, were significantly up-regulated in HIV+ SDE+ patients compared to HIV- SDE+ patients (P < .05). Conversely, the CD4/CD8 ratio was significantly down-regulated in HIV+ SDE+ patients compared to HIV- SDE+ patients (P < .05). HIV infection confers distinct clinical phenotypes and immune inflammatory mechanisms in SDE. Sustained EBV and CMV activation, unbalanced Th2/Th1 and overactive CD8+ T cells mediating a pro-inflammatory response could act as distinct mechanisms in the aggravation of SDE in HIV+ SDE+ patients.

To explore possible associations between maternal use of micronutrient supplements and the subsequent vitamin levels and symptoms in offspring with autism spectrum disorder (ASD), a total of 416 children with ASD and 201 typically developing (TD) children were enrolled. The children born to mothers without folic acid (FA) and micronutrient supplementation during pregnancy had more severe social cognition impairments, social communication impairments, autism behaviour mannerisms, developmental delays in adaptive and gross motor behaviour and gastrointestinal problems than children born to mothers who used FA and micronutrient supplements (P＜0.05). Interestingly, there was an association between maternal micronutrient supplementation and vitamin A (VA), vitamin D (VD) and folate levels in the ASD children (P

Natural products (NPs) and their derivatives play a pivotal role in drug discovery due to their complexity and diversity. The strategies to rapidly generate NP-like compounds offer unique opportunities to access bioactive compounds. Here we present a new approach, precursor-assisted biosynthesis (PAB), for the creation of NP-like compounds by combination of artificial supplementation of common precursors and divergent post-modifications of precursor-deficient fungi. This method was applied to construct a meroterpenoid-like compound collection containing 43 compounds with diverse molecular scaffolds. Extensive bioactive screening of the collection revealed novel STING (stimulator of interferon genes) inhibitors, cytotoxic and antifungal compounds. This result indicates that PAB is an effective methodology for producing compound collections for the purpose of drug discovery.

The development of new drugs for nonalcoholic steatohepatitis (NASH) is a current focus of research in the management of liver disease. Here we provided an overview of NASH drug pipelines and the challenges faced in conducting phases II and III clinical trials. These challenges include the selection and definition of research populations, rational selection of study end-points, choice of noninvasive diagnostic indicators, accounting for confounding factors and safety assessments. Furthermore, we discussed how to establish guidelines for study design and end-points in complex clinical trials of anti-NASH drugs.

The Escherichia coli-derived tyrosyl-tRNA synthetase was the first enzyme engineered for genetic code expansion in a eukaryotic system but can charge only a limited set of structurally simple noncanonical amino acids. In contrast, the thermophilic Methanocaldococcus jannaschii-derived tyrosyl-tRNA synthetase mutants, used in only a prokaryotic system, can charge a surprisingly large set of structurally diverse ncAAs, due to their remarkable structural ability to tolerate mutations. Inspired by this, we characterized a new class of tyrosyl-tRNA synthetase/tRNATyr pairs from thermophilic bacterium Geobacillus stearothermophilus, which is homologous to the E. coli tyrosyl-tRNA synthetase but with better thermostability. This new pair is both orthogonal in mammalian cells and in Saccharomyces cerevisiae for genetic code expansion and can charge a diverse set of ncAAs with a comparable cellular efficiency, better specificity, and lower background, as compared to those of its E. coli homologue. This thermostable enzyme provides an alternative scaffold for synthetase library screening or evolution to genetically encode more structurally complex ncAAs in eukaryotic cells.

Methotrexate (MTX) as an anti-inflammatory drug for the treatment of rheumatoid arthritis (RA) through oral and injectable administration is still problematic in the clinic. Herein, a MTX-loaded thermal-responsible flexible liposome (MTFL) incorporated within a carbomer-based gel was prepared as a novel transdermal agent (MTFL/Gel) for effective treatment of RA. It was found that MTFL had an average size of approximately 90 nm, which could rapidly release the drug under thermal conditions. The prepared MTFL/Gel could remarkably increase the MTX skin permeation as compared with free MTX, which was possibly due to the deformable membrane of flexible liposomes. Moreover, the results suggested MTFL/Gel could lead to a remarkably enhanced RA treatment when in combination with microwave hyperthermia. The superior ability of MTFL/Gel to alleviate RA response was attributed to the excellent skin permeation, thermal-responsible drug release, and synergistic anti-arthritic effect of MTX chemotherapy and microwave-induced hyperthermia therapy. Overall, the MTFL/Gel with dual deformable and thermal-responsible performances could be used as a novel promising transdermal agent for enhanced treatment of RA.

BACKGROUND miRNAs and mRNAs have been significantly implicated in tumorigenesis and served as promising prognostic biomarkers for human cancer. Hence, this study was aimed to develop the pivotal miRNA biomarkers-based prognostic signature for salivary adenoid cystic carcinoma. METHODS The miRNA and mRNA expression data were integrated from the gene expression omnibus database to study their involvement in salivary adenoid cystic carcinoma development and progression. Gene ontology and kyoto encyclopedia of genes and genomes were conducted to analyze the biological pathways. Reverse transcription-quantitative PCR was used to verify the expression of selected miRNAs in salivary adenoid cystic carcinoma and corresponding normal tissues. RESULTS There were 386 differentially expressed genes: 158 upregulated and 228 downregulated genes and 102 differentially expressed miRNAs: 78 upregulated and 24 downregulated miRNAs in the salivary adenoid cystic carcinoma samples. A miRNA-mRNA network containing 11 miRNAs and 199 genes was subsequently constructed. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis revealed that the genes targeted by the 11 miRNAs were mostly involved in tumor-related pathways and processes, such as miRNAs in cancer, focal adhesion, neurotrophin signaling pathway, and the PI3K-Akt signaling pathway. Among them, 4 miRNAs (miR-375, miR-494, miR-34c-5p, and miR-331-3p) were selected to verify by reverse transcription-quantitative PCR in 36 pairs of collected salivary adenoid cystic carcinoma and adjacent nontumor samples. Overall survival analysis revealed that the higher expression of miR-331-3p was significantly associated with a worst overall survival and multivariate Cox regression analysis suggested that hsa-miR-331-3p could be an independent prognostic factor for salivary adenoid cystic carcinoma. CONCLUSION Our results revealed that 4-miRNAs signature was a powerful prognostic biomarker for salivary adenoid cystic carcinoma, which provide a basis for exploring deeper mechanisms regarding the progression of salivary adenoid cystic carcinoma, and leading to the development of potential therapeutic strategies.

There have been considerable concerns regarding the effects of air pollution on health and economy over the past decades across the world. As insurance coverage has been closely related to household welfare, we aim to investigate the influence of air pollution, in particular, the sulfur dioxide (SO2) pollution on household purchases of commercial health insurance using data from the 2017 China Household Financial Survey (CHFS). The results show that the rise in SO2 emission has a significant positive association with tendency of residents to participate in commercial health insurance. The possibility of household commercial health insurance purchasing increases by 4% per 1,000 tons of SO2 emission. In addition, the proportion of commercial health insurance expenditure in household annual income increases by 29% per 1,000 tons of SO2 emission. The effects are also found to differ among resident groups. Residents in eastern parts of China are more likely to buy commercial health insurance facing SO2 pollution compared to those in western parts of China; people with higher income are more likely to be affected compared to those with lower income; families with the household head being female are more likely to be affected compared to those with the household head being male. This research provides baseline information on the formulation and implementation of future operation strategy in commercial health insurance companies of China.

Background During the recovery period of general anesthesia, patients are disturbed by residual anesthetic drugs, manifesting as clinical signs of confusion, drowsiness and disorientation, and even abnormal psychology and limb agitation at varying degrees in severe cases. These stress reactions are detrimental to the postoperative recovery, which can be life-threatening. Operating room nursing intervention (ORNI) is a novel nursing model that prevents stress reactions during the recovery period of general anesthesia. However, whether ORNI can improve the psychological condition and reduce the incidence of emergence agitation in the recovery period of general anesthesia remains controversial. Therefore, this study aims to evaluate the effect of ORNI on the psychological status and incidence of emergence agitation in the recovery period of general anesthesia through a systematic review and meta-analysis, thus providing clinical evidence to support it. Methods Randomized controlled trials reporting the effect of ORNI on the recovery period of general anesthesia published before October 2021 will be searched in the Chinese Scientific Journal Database, China National Knowledge Infrastructure Database, Wanfang, China Biomedical Literature Database, PubMed, Embase, the Cochrane Library, and Web of Science. Eligible literatures will be screened out according to inclusion and exclusion criteria, and their quality will be assessed using the Cochrane Risk of Bias Assessment Tool. Meta-analysis will be performed using Revman 5.4 software. Results This study will evaluate the effect of the ORNI on the recovery period of general anesthesia by calculating the incidence of emergence agitation, and grading the self-rating anxiety scale and self-rating depression scale scores. Conclusion This study will provide a reliable evidence-based basis for the application of ORNI in the recovery period of general anesthesia. Osf registration number DOI 10.17605/OSF.IO/P3A4T.

Background Unexpected spontaneous ovulation typically occurs in patients with poor ovarian response (POR); however, reliable predictors are lacking. We analyzed explore the predictive value of decreased serum estradiol (E2) levels on the day after human chorionic gonadotropin (hCG) trigger during in vitro fertilization (IVF) cycles. Methods We retrospectively analyzed clinical data (n = 978) in IVF cycles between 2017 and 2020. According to decreased ratios of E2 levels (△E2%) between day 1 and day 0 of hCG trigger, patients were divided into: ≤10% (group A), 10–20% (group B), and ≥ 20% (group C). Basic characteristics and laboratory data were compared using analysis of variance or Mann–Whitney U-test. Logistic regression and receiver operating characteristic (ROC) curve analyses were used to assess the relationship between △E2% and spontaneous unexpected ovulation. Fresh embryo transfer cycles in groups A, B, and C were subgrouped as A1, B1, and C1, respectively; clinical outcomes were compared. Results Mean E2 and luteinizing hormone (LH) levels, ratio of premature LH peak and high progesterone levels, time interval between hCG trigger and oocyte retrieval, number of follicles ≥ 11 mm in diameter, and dose regimen of gonadotropin among the three groups showed significant differences (P P for trend 10 mIU/mL) or high progesterone level (> 1.0 ng/mL) on the day of hCG, area under ROC curve (AUC) was 0.849 (95 % CI, 0.764–0.934, P P P > 0.05). Conclusions E2 levels on the day after hCG trigger are valuable for predicting unexpected ovulation. However, their decreased levels do not directly affect clinical pregnancy outcomes.

Background: Frequent/urgent urination is an event of multifactorial origin where involuntary leakage of urine occurs. Epidemiological study of this condition is of high importance due to its negative impact on the psychological, physical, and social well-being of the victims.Objective: This cross-sectional study aimed to investigate the prevalence of frequent/urgent urination in older adults in China.Method: In this study, a face-to-face questionnaire survey was conducted between April 2019 and August 2019 among 4,796 older adult populations in the communities of Tianjin jizhou and Xiamen jimei of China. Descriptive analysis, univariate regression, and all statistics were conducted in IBM SPSS v22. The count data were analyzed by chi-square test. P < 0.05 was considered statistically significant.Results: In the total investigated population, the prevalence of frequent or urgent urination was found in 1,164 patients (24.3%) where 31.7% (664/2,097) were male patients and 18.7% (500/2,699) were female patients, having a male-to-female ratio of 1.7:1. The prevalence was higher in the 70- to 84-year-old group (men: 33.3–34.8%, women 19.5–20.8%), whereas it was relatively low in the 65- to 69-year-old group and in older adults over 85 years of age (men 28.8, 30.3%, women 16.7, 18.5%, respectively). In terms of the course of the disease, among the population aged 65 years and above, 17.3% men and 9.9% women had frequent urination/urgency lasting for 1–4 years; 5–9 years in about 4.5% population (7.4% men and 4.2% women); 10–19 years in 4.9% men and 2.3% women; and more than 20 years duration in 1.6% men and 1.9% women. On the severity scale, mild frequent/urgent urination was observed in 24.6% of men and 15.4% women of Chinese older adults. Moderate cases were observed in 6.3% of men and 2.9% of women, whereas severe cases were found in 0.8% men and 0.2% women. Benign prostatic hyperplasia (BPH)/hypertrophy was the main risk factor for frequent/urgent urination in Chinese older adult men (P < 0.001). Obesity, hypertension, diabetes, heart disease, anxiety, depression, constipation, and brain injury were the other risk factors for frequent/urgent urination in Chinese older adult men and women. The results of this survey showed that smoking or drinking habits did not increase the prevalence of frequent/urgent urination in Chinese older adults.Conclusions: According to the results of this survey, the prevalence rate of frequent/urgent urination is high, and the course of the disease is long in Chinese older adults. BPH and depression, anxiety, and age-related chronic diseases increase the risk of frequent/urgent urination in Chinese older adults.

Objective In China, polyene phosphatidylcholine (PPC) is widely used to treat alanine aminotransferase (ALT) elevation associated with various liver diseases. Here, we assessed the efficacy and safety of PPC in treating drug-induced liver injury (DILI). Methods Data from a multicenter retrospective cohort study (DILI-R) were analyzed to compare PPC and magnesium isoglycyrrhizinate (MgIG) for treatment of DILI. We used the Roussel Uclaf causality assessment method (RUCAM) to evaluate patients with DILI. Patients with RUCAM scores ≥6 were included in the study, while those with RUCAM scores Results Among the DILI patients, 64 of 183 (34.97%) achieved normal ALT levels after treatment in both the PPC and the MgIG groups. Conclusion There were no significant differences in safety biomarkers including serum creatinine, blood urea nitrogen, white blood cells, platelets, hemoglobin, and albumin between patients treated with PPC or MgIG. The safety and efficacy of these two agents for treatment of DILI were comparable.

Objective: This study was designed to identify the key pathway and immune cells for hypertrophic cardiomyopathy (HCM) via bioinformatics analyses of public datasets and evaluate the significance of immune infiltration in the pathogenesis of HCM.Methods: Expressional profiling from two public datasets (GSE36961 and GSE141910) of human HCM and healthy control cardiac tissues was obtained from the GEO database. After data preprocessing, differentially expressed genes (DEGs) were then screened between HCM and healthy control cardiac tissues in parallel. Gene Ontology, pathway functional enrichment, and gene set enrichment analysis were performed using DAVID and GSEA application. The compositional patterns of immune and stromal cells in HCM and control cardiac tissues were estimated based on the merged data using xCell. Protein–protein interaction (PPI) network and module analyses were constructed by STRING and Cytoscape applications. Gender-based expressional differences analyses were also conducted to explore gender differences in HCM. GSE130036 and clinical samples were used for verification analyses.Results: A total of 310 DEGs were identified. Upregulated DEGs were mainly enriched in “adhesion” and “apoptotic process” in the biological process. As for the downregulated DEGs, “inflammatory response,” “innate immune response,” “phagosome,” and “JAK-STAT signaling pathway” were highly enriched. Immune infiltration analyses suggested that the scores of macrophages, monocytes, DC, Th1, Treg, and plasma cells in the HCM group were significantly decreased, while CD8+ T cells, basophils, fibroblasts, and platelets were significantly enriched. Module analyses revealed that STAT3, as the hub genes in HCM together with LYVE1+CD163+ macrophages, may play a key role in the pathogenesis of HCM while there were no obvious gender differences in the HCM samples from selected datasets. Verification analyses performed on GSE130036 and clinical samples showed a strong positive correlation (Spearman correlation = 0.7646) and a good co-localization relationship between LYVE1 and CD163, suggesting the potential function of LYVE1+CD163+ macrophages in maintaining the homeostasis of cardiac tissue.Conclusion: STAT3-related pathway and CD163+LYVE1+ macrophages were identified as the potential key pathway and immune cells in HCM and may serve as interesting targets for further in-depth research.

Background Herbal and Dietary Supplements (HDS) are capable of causing liver injury, however, the extent of HDS-induced liver injury compared to western medication (WM)-induced liver injury has not been well studied. Methods This was a three-year, retrospective study from 308 centers across Mainland China. 3,877 patients with liver injury due to HDS and 3,796 patients with liver injury due to WM were analyzed. Demographic and clinical characteristics, implicated agents, and severity of liver injury were analyzed using descriptive statistics. Results The HDS group was older (average age 47.65 ± 14.8 years) and had more females (57.92%). The latency to onset of liver injury was greater in the HDS group than in the WM group (41 vs. 35 days, P

Background Vitamin A deficiency (VAD) and sleep disturbances have been reported in children with autism spectrum disorder (ASD). The influence of vitamin A (VA) levels on sleep regulation and sleep disturbances in ASD has garnered concern. The present study aimed to characterize the association of VA levels with sleep disturbances in children with ASD. Methods This cross-sectional study compared children with ASD (n = 856) to typically developing children (TDC; n = 316). We used the Children’s Sleep Habits Questionnaire to assess sleep disturbances, Childhood Autism Rating Scale to evaluate the severity of autism symptoms, and Autism Behavior Checklist and Social Responsiveness Scale to assess autism behaviors. Serum VA levels were estimated using high-performance liquid chromatography. Multivariable linear regression and two-way analysis of variance were performed to investigate if VAD was related to sleep disturbances in children with ASD. Results Children with ASD had lower serum VA levels and a higher prevalence of sleep disturbances than TDC did. The incidence of VAD in ASD children with sleep disturbances was higher, and the symptoms more severe than those without sleep disturbances and TDC. Interestingly, the interaction between VAD and sleep disturbances was associated with the severity of autism symptoms. Conclusion VAD and sleep disturbances are associated with the core symptoms of ASD in children. Regular monitoring of sleep and VA levels may be beneficial for children with ASD. Trial registration Chinese Clinical Trial Registry, registration number: ChiCTR-ROC-14005442, registration date: December 9th 2014.

Glioma is the most common type of primary tumor in the central nervous system, and the molecular mechanisms remain elusive. N-myc downstream-regulated gene (NDRG) family is reported to take part in the pathogenesis of various diseases, including some preliminary exploration in glioma. However, there has been no bioinformatics analysis of NDRG family in glioma yet. Herein, we focused on the expression changes of NDRGs with their value in predicting patients' prognoses, upstream regulatory mechanisms (DNA mutation, DNA methylation, transcription factors, and microRNA regulation) and gene enrichment analysis based on co-expressed genes with data from public databases. Furthermore, the expression pattern of NDRGs was verified by the paired glioma and peritumoral samples in our institute. It was suggested that NDRGs were differentially expressed genes in glioma. In particular, the lower expression of NDRG2 or NDRG4 could serve as a predictor of higher grade tumor and poorer prognosis. Also, NDRGs might play a crucial role in signal transduction, energy metabolism, and cross-talk among cells in glioma, under the control of a complex regulatory network. This study enables us to better understand the role of NDRGs in glioma and with further research, it may contribute to the development of glioma treatment.

AIMS This study aimed to create a structural equation model to evaluate the associations among demographic factors, health education, breast cancer-related knowledge, attitudes, and breast self-examination behavior among Chinese female college students. METHODS A survey was undertaken using a self-administered questionnaire and targeting 2233 students from Eastern China. Structural equation modeling with the bootstrap approach was utilized to estimate the interrelationships and the strength of the associations among measured variables based on the hypothetical model. RESULTS Among the total participants, 14.7% of the female college students reported having performed breast self-examination. The final structural equation model showed highly satisfactory fitness on indices. Breast self-examination behavior was significantly linked to demographic factors, breast cancer related-knowledge, attitudes, and health education. Health education had the greatest influence on breast self-examination behavior. In addition, breast cancer related-knowledge was significantly associated with demographic factors and health education. Health education and knowledge all significantly affected attitudes towards breast cancer. CONCLUSION Breast self-examination behavior was influenced by demographic factors, breast cancer related-knowledge, attitudes towards breast cancer, and health education in a sample of female college students in China. Health education was the most important predictor of breast self-examination behavior.

The aim of this study was to apply machine learning methods to deeply explore the risk factors associated with adverse drug events (ADEs) and predict the occurrence of ADEs in Chinese pediatric inpatients. Data of 1,746 patients aged between 28 days and 18 years (mean age = 3.84 years) were included in the study from January 1, 2013, to December 31, 2015, in the Children’s Hospital of Chongqing Medical University. There were 247 cases of ADE occurrence, of which the most common drugs inducing ADEs were antibacterials. Seven algorithms, including eXtreme Gradient Boosting (XGBoost), CatBoost, AdaBoost, LightGBM, Random Forest (RF), Gradient Boosting Decision Tree (GBDT), and TPOT, were used to select the important risk factors, and GBDT was chosen to establish the prediction model with the best predicting abilities (precision = 44%, recall = 25%, F1 = 31.88%). The GBDT model has better performance than Global Trigger Tools (GTTs) for ADE prediction (precision 44 vs. 13.3%). In addition, multiple risk factors were identified via GBDT, such as the number of trigger true (TT) (+), number of doses, BMI, number of drugs, number of admission, height, length of hospital stay, weight, age, and number of diagnoses. The influencing directions of the risk factors on ADEs were displayed through Shapley Additive exPlanations (SHAP). This study provides a novel method to accurately predict adverse drug events in Chinese pediatric inpatients with the associated risk factors, which may be applicable in clinical practice in the future.