Balanced medial-lateral wall vs selective 3-wall orbital decompression for sight-threatening Graves's orbitopathy: a clinical retrospective cohort study from 2016 to 2022.

PURPOSE: Although urgent orbital decompression surgery for sight-threatening Graves' orbitopathy unresponsive to available medical treatments continues to evolve, post-operative new-onset or worsened pre-operative strabismus or diplopia remains a significant complication. At present, the optimal surgical technique remains debatable. Here, we sought to compare long-term outcomes after balanced medial-lateral wall versus selective 3-wall decompression as an urgent treatment for unresponsive sight-threatening GO. METHODS: This retrospective study examined the post-operative outcome of 102 eyes (57 patients) that underwent urgent orbital decompression for sight-threatening GO. Treatment effectiveness was measured by visual acuity, proptosis, perimetry, and strabismus/diplopia, while fundus findings were detected by fundus color photography and optical coherence tomography and followed up for more than 12 months. RESULTS: Fifty-seven patients (102 orbits) with an average age of 52.7 ± 10.2 years were evaluated. Balanced medial-lateral wall (BMLW-OD) or selective 3-wall decompression(S3W-OD) were performed in 54 and 48 eyes, respectively. Twelve months after orbital decompression, all parameters significantly improved in both groups, including best-corrected visual acuity (BCVA), mean defect of visual field (VF-MD), pattern standard deviation of visual field (VF-PSD), and proptosis (all P < 0.01). However, new-onset esotropia occurred in 25.8% and 3.8% of patients who underwent BMLW-OD surgery or S3W-OD, respectively. Moreover, 6.5% and 38.5% of patients improved after decompression in the medial-lateral wall decompression group and the selective 3-wall decompression group, respectively. CONCLUSIONS: We demonstrated that S3W-OD provides a lower rate of new-onset strabismus/diplopia as compared with BMLW-OD surgery, while still allowing for satisfactory visual outcomes. TRIAL REGISTRATION NUMBER:  : NCT05627401. Date of registration: November 25, 2022.

Sex- and reproductive status-specific relationships between body composition and non-alcoholic fatty liver disease.

BACKGROUND: Sex and reproductive status differences exist in both non-alcoholic fatty liver disease (NAFLD) and body composition. Our purpose was to investigate the relationship between body composition and the severity of liver steatosis and fibrosis in NAFLD in different sex and reproductive status populations. METHODS: This cross-sectional study included 880 patients (355 men, 417 pre-menopausal women, 108 post-menopausal women). Liver steatosis and fibrosis and body composition data were measured using FibroScan and a bioelectrical impedance body composition analyzer (BIA), respectively, and the following parameters were obtained: liver stiffness measurement (LSM), controlled attenuation parameter (CAP), waist circumference (WC), body mass index (BMI), percent body fat (PBF), visceral fat area (VFA), appendicular skeletal muscle mass (ASM), appendicular skeletal muscle mass index (ASMI), fat mass (FM), fat free mass (FFM), and FFM to FM ratio (FFM/FM). Multiple ordinal logistic regression (MOLR) was used to analyze the independent correlation between body composition indicators and liver steatosis grade and fibrosis stage in different sex and menopausal status populations. RESULTS: Men had higher WC, ASM, ASMI, FFM, and FFM/FM than pre- or post-menopausal women, while pre-menopausal women had higher PBF, VFA, and FM than the other two groups (p < 0.001). Besides, men had greater CAP and LSM values (p < 0.001). For MOLR, after adjusting for confounding factors, WC (OR, 1.07; 95% CI, 1.02-1.12; P = 0.011) and FFM/FM (OR, 0.52; 95% CI, 0.31-0.89; P = 0.017) in men and visceral obesity (OR, 4.16; 95% CI, 1.09-15.90; P = 0.037) in post-menopausal women were independently associated with liver steatosis grade. WC and visceral obesity were independently associated with liver fibrosis stage in men (OR, 1.05; 95% CI, 1.01-1.09, P = 0.013; OR, 3.92; 95% CI, 1.97-7.81; P < 0.001, respectively). CONCLUSIONS: Increased WC and low FFM/FM in men and visceral obesity in post-menopausal women were independent correlates of more severe liver steatosis. In addition, increased WC and visceral obesity were independent correlates of worse liver fibrosis in men. These data support the sex- and reproductive status-specific management of NAFLD.

Comprehensive transcriptomic profiling and mutational landscape of primary gastric linitis plastica.

BACKGROUND: Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined. METHODS: We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP. RESULTS: Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity. CONCLUSIONS: We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment.

In-situ preparation of CuO nanoparticles decorated In2O3 pn heterojunction composite for the photoelectrochemical detection of ornidazole.

The eco-friendly synthesis of metal oxides pn junction composite with high visible light absorption and its photoelectrochemical monitoring on antibiotics is reported. The In2O3-CuO pn heterojunction composite was successfully prepared by in-situ hydrothermal decoration of CuO on the prepared In2O3 using a simple reflux method. The obtained nanorods like In2O3-CuO pn heterojunction exhibited high conductivity with excellent stability for the facilitated photoelectrochemical detection of ornidazole (ONZ) that plays a role in aquatic toxicology. The photo-stability and optical characteristics of the In2O3-CuO heterojunction composite were analyzed through photocurrent and UV-visible studies. Mechanism of ONZ signaling has been proposed with appropriate band levels derived by Mott-Schottky analysis. An optimized In2O3-CuO heterojunction detects ONZ in the range 0.05-65.3 nM with 0.0092 nM as the limit of detection at - 0.45 V (vs. Ag/AgCl) working potential. The practical applicability of the sensor device was tested in chicken meat, human urine, and lake water samples containing ONZ. The recoveries of real samples were above 95% and results obtained were compared with electrochemical methods.

Polyamine synthesis enzyme AMD1 is closely associated with tumorigenesis and prognosis of human gastric cancers.

Adenosylmethionine decarboxylase 1 (AMD1) is a key enzyme involved in biosynthesis of polyamines including spermidine and spermine. The potential function of AMD1 in human gastric cancers is unknown. We analyzed AMD1 expression level in 319 human gastric cancer samples together with the adjacent normal tissues. The protein expression level of AMD1 was significantly increased in human gastric cancer samples compared with their corresponding para-cancerous histological normal tissues (P < 0.0001). The expression level of AMD1 was positively associated with Helicobactor pylori 16sRNA (P < 0.0001), tumor size (P < 0.0001), tumor differentiation (P < 0.05), tumor venous invasion (P < 0.0001), tumor lymphatic invasion (P < 0.0001), blood vessel invasion (P < 0.0001), and tumor lymph node metastasis (TNM) stage (P < 0.0001). Patients with high expression of AMD1 had a much shorter overall survival than those with normal/low expression of AMD1. Knockdown of AMD1 in human gastric cancer cells suppressed cell proliferation, colony formation and cell migration. In a tumor xenograft model, knockdown of AMD1 suppressed the tumor growth in vivo. Inhibition of AMD1 by an inhibitor SAM486A in human gastric cancer cells arrested cell cycle progression during G1-to-S transition. Collectively, our studies at the cellular, animal and human levels indicate that AMD1 has a tumorigenic effect on human gastric cancers and affect the prognosis of the patients.

[Post-marketing intensive safety monitoring of Injection of Xuesaitong (lyophilized) in 30097 cases].

To investigate the safety of Injection of Xuesaitong(lyophilized) in clinical "real world" application, including the types, incidence, as well as the severity and treatment measures of adverse reactions/adverse events. This will serve as a basis for hospitals and enterprises to develop risk control measures. A prospective, multi-center, and large-sample hospital centralized monitoring method was used to conduct post-marketing safety monitoring of Injection of Xuesaitong(lyophilized) in medical institutions nationwide. Paper case report forms were adopted to collect general information, medication and adverse reaction information of patients using Injection of Xuesaitong(lyophilized). Data analysis was performed by using SAS 9.1 software. The study included 79 hospitals with 30 097 patients. 199 cases of adverse events were found in patients administered with Injection of Xuesaitong(lyophilized), a total of 206 times. Among 199 cases, 40 of them showed adverse reactions, accounting for an overall incidence of 0.13% and 95%CI[0.09%,0.17%], which was an occasional grade. There were 38 cases of mild adverse reactions, accounting for 95.0%, 2 cases of moderate adverse reactions, accounting for 5.0%. Adverse reaction symptoms were relieved in six patients, accounting for 15.0% of the total number of adverse reactions, adverse reaction symptoms disappeared in 34 cases, with an overall percentage of 85.0%. The results of the study showed the adverse reactions in patients using Injection of Xuesaitong(lyophilized) were rare and mild, with a good prognosis. Therefore, clinical administration of Injection of Xuesaitong(lyophilized) is relatively safe.

[Analysis of Injection of Xuesaitong (lyophilized) in 30097 cases in real world].

To investigate the extensive application of Injection of Xuesaitong(lyophilized) in clinical real world study, and provide basis for clinical guidance on rational drug use and improvement of drug instructions. A prospective, multi-center, large-sample hospital centralized monitoring method was adopted to collect the general information and medication information of all patients who received Injection of Xuesaitong(lyophilized) during the study period in the respective monitoring units. Data analysis was performed using SAS 9.1 software. This study included 79 hospitals, with 30 097 patients being recruited. The patients who met the indications for stroke and hemiplegia accounted for 31.18%, those who experienced indications of chest pain and heartache accounted for 23.15%, and patients with central retinal vein occlusion indication accounted for 0.53%. The minimum single dose of Injection of Xuesaitong(lyophilized) was 20 mg, the maximum single dose was 1 000 mg, and the average single dose was(383.31±78.10) mg. 69.96% of the patients used 0.9% sodium chloride as the menstruum, 28.78% of the patients used 5% glucose as the menstruum, and 0.19% of the patients used 10% glucose as the menstruum. The minimum time for Injection of Xuesaitong(lyophilized) to dissolve is 0 min, 120 min maximally, and(14.26±13.73) min on an average basis. Patients using Injection of Xuesaitong(lyophilized) by intravenous drip accounted for 99.93%, with a slowest drip rate of 10 drops per min, fastest drip rate of 80 drops per min, and an average of(43.91±10.77) drops per min. Injection of Xuesaitong(lyophilized) was used for a minimum of 1 day and a maximum of 80 days, with an average of(8.22±5.12) days. Combined use with other injections accounted for 80.67%, 47.14% of them flushed the tube and 3.31% of them replaced infusion sets. The study found 40 cases of adverse reactions in patients with Injection of Xuesaitong(lyophilized), with an overall incidence of 0.13%(0.09% to 0.17%) for adverse reactions. In the real world application, the usage of Injection of Xuesaitong(lyophilized) basically meets the requirement of drug instructions in terms of indications, dosages, and methods of administration. However, it still needs to be improved in standardizing the selection of the menstruum, drip rate, course of treatment, and the combined usage of medicine.

Cell-Free RNA Content in Peripheral Blood as Potential Biomarkers for Detecting Circulating Tumor Cells in Non-Small Cell Lung Carcinoma.

Circulating tumor cells (CTCs) have been implicated in tumor progression and prognosis. Techniques detecting CTCs in the peripheral blood of patients with non-small cell lung carcinoma (NSCLC) may help to identify individuals likely to benefit from early systemic treatment. However, the detection of CTCs with a single marker is challenging, owing to low specificity and sensitivity and due to the heterogeneity and rareness of CTCs. Herein, the probability of cell-free RNA content in the peripheral blood as a potential biomarker for detecting CTCs in cancer patients was investigated. An immunomagnetic enrichment of real-time reverse-transcription PCR (RT-PCR) technology for analysis of CTCs in NSCLC patients was also developed. The mRNA levels of four candidate genes, cytokeratin 7 (CK7), E74-like factor 3 (ELF3), epidermal growth factor receptor (EGFR), and erythropoietin-producing hepatocellular carcinoma receptor B4 (EphB4) that were significantly elevated in tumor tissues and peripheral blood mononuclear cells (PBMCs) were determined. The expression of CK7 and ELF3 in tumor tissues and EGFR in PBMCs was associated with lymph node metastasis (all p < 0.05). The expression of CK7 in PBMCs was correlated with age and EphB4 in PBMCs correlated with histopathological type, respectively (all p < 0.05). The expression of all four genes in tumor tissues and PBMCs was significantly correlated with the clinical stage (all p < 0.01). Survival analysis showed that the patients with enhanced expression of CK7, ELF3, EGFR, and EphB4 mRNA in PBMCs had poorer disease-free survival (DFS) and overall survival (OS) than those without (all p < 0.0001). The present study showed that this alteration of cell-free RNA content in peripheral blood might have clinical ramifications in the diagnosis and treatment of NSCLC patients.

Changes in the Biomechanical Properties of Corneal Stromal Lens after Collagen Crosslinking Induced by EDC-NHS.

Introduction: To evaluate the changes of lens antidilatation, antiedema, and antienzymolysis ability after different concentrations of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide (EDC-NHS)-induced collagen cross-linking. Methods: Corneal stromal lenticules (n = 100) obtained from small incision lenticule extraction (SMILE) procedures were divided into 5 groups: no treatment (control); EDC/NHS (5%/2.5%); EDC/NHS(5%/5%); EDC/NHS (10%/5%); riboflavin and ultraviolet-A light (UVA). Collagen crosslinking was induced using EDC-NHS and UVA. Biomechanical assessments including inflation test, enzymatic degradation resistance, and light transmittance were evaluated posttreatment. Results: (1) Lenticule apex displacement ranked: control Group > UVA Group > Group (5%/5%) > Group (5%/2.5%) > Group (10%/5%) (Friedman test, p < 0.0001). (2) Light transmittance was significantly higher in the crosslinked groups versus control, with EDC/NHS superior to UVA riboflavin. After 15 minutes in PBS, light transmittance decreased due to swelling; however, crosslinked groups maintained significantly higher transmittance versus control. (3) Following crosslinking, enzymatic resistance improved significantly, with the EDC-NHS crosslinking group was significantly better than the UVA cross-linking group. Conclusions: EDC/NHS crosslinking enhanced lenticule stiffness, antiedema, and enzymatic resistance and without compromising the transparency of the lens. Moreover, EDC/NHS crosslinking efficacy exceeded UVA riboflavin crosslinking in improving lenticule biomechanical properties.

Association between thyroid function and nonalcoholic fatty liver disease: a dose-response meta-analysis.

Background: Thyroid hormones (THs) have been found that it is closely associated with the onset and progression of non-alcoholic fatty liver disease (NAFLD). However, the current study could not verify the intrinsic relationship between thyroid hormones and NAFLD, which requires further research. Methods: The searches of studies reported both TH level in serum and NAFLD were performed in PubMed, Web of Science, Cochrane Library, and Embase databases. We combined an overall meta-analysis with a dose-response meta-analysis to assess the correlation and dose-response relationship between thyroid function levels and the risk of NAFLD. Results: Overall, 10 studies were included with a total of 38,425 individuals. We found that the non-linear dose-response model showed that for every 1 ng/dL increase in FT4, the risk of NAFLD was reduced by 10.56% (p=0.003). The odds ratios (ORs) for NAFLD with high free triiodothyronine (FT3) exposure compared to those with low FT3 were 1.580 (95% CI 1.370 to 1.830, I2 = 0.0%, p<0.001) in the overall meta-analysis. The continuous variable meta-analysis indicated that individuals with high levels of TSH (SMD=1.32, 95% CI 0.660 to 1.970, p<0.001) had significantly higher levels of liver fibrosis than those with low levels. Conclusions: Our findings only validate that there is a correlation between the occurrence of NAFLD and abnormal levels of THs, and it is expected that more observational studies will still be conducted in the future to further demonstrate the relationship between thyroid hormones and NAFLD. Trial registration: Registered number in PROSPERO: CRD42023405052.

Review of Atlanticus Scudder, 1894 (Orthoptera: Tettigoniidae: Tettigoniinae) from China, with description of 27 new species.

Atlanticus Scudder illustrates a disjunctive distribution comprising 1 subgenus and 10 valid species from eastern North America and 2 subgenera and 14 valid species from eastern Asia. Several authors also predicted that it would appear that China was rich in new species of the genus Atlanticus. Based on investigation of male stridulatory apparatus, as well as previously used characters, including male and female abdominal apex and measurements of various structures, we present a taxonomic account of 43 species of Atlanticus from China. Twenty-seven species of Atlanticus new to science are described. Erroneous synonyms are noted, based on examination of topotypes. Atlanticus changi Tinkham, 1941 and Atlanticus pieli Tinkham, 1941 are valid species and not synonyms of Atlanticus kiangsu Ramme, 1939. Atlanticus jeholensis Mori, 1935 is also valid and not a synonym of Atlanticus sinensis Uvarov, 1924. Moreover, the supposedly important character, i.e., length comparison between male pronotum and tegmen, is not suitable for differentiating two subgenera of Atlanticus, because it is easy to cause confusion. In contrast, the architecture of the male tegmen is a useful character to differentiate the two subgenera. The previous mentioned Species Groups and the corresponding descriptions are also studied. Necessary illustrations are provided.

Exploring the Mechanism of Yi-Jing Decoction in Treating Polycystic Ovary Syndrome by Using Network Pharmacology.

BACKGROUND: Yi-Jing decoction (YJD), a traditional Chinese medicine prescription, has been reported to be effective in the treatment of polycystic ovary syndrome (PCOS). However, the underlying mechanisms of YJD in treating PCOS are still unclear. OBJECTIVE: In the present work, the effective ingredients of YJD and their treatment mechanisms on PCOS were systematically analyzed. METHODS: The effective ingredients of YJD and targets of PCOS were selected from public databases. The network pharmacology method was used to analyze the ingredients, potential targets, and pathways of YJD for the treatment of PCOS. RESULTS: One hundred and three active ingredients were identified from YJD, of which 82 were hit by 65 targets associated with PCOS. By constructing the disease-common targetcompound network, five ingredients (quercetin, arachidonate, beta-sitosterol, betacarotene, and cholesterol) were selected out as the key ingredients of YJD, which can interact with the 10 hub genes (VEGFA, AKT1, TP53, ALB, TNF, PIK3CA, IGF1, INS, IL1B, PTEN) against PCOS. These genes are mainly involved in prostate cancer, steroid hormone biosynthesis, and EGFR tyrosine kinase inhibitor resistance pathways. In addition, the results of molecular docking showed that the ingredients of YJD have a good binding affinity with the hub genes. CONCLUSION: These results demonstrate that the treatment of PCOS by YJD is through regulating the levels of androgen and insulin and improving the inflammatory microenvironment.

Retrospective analysis of 217 fatal intoxication autopsy cases from 2009 to 2021: temporal trends in fatal intoxication at Tongji center for medicolegal expertise, Hubei, China.

This retrospective analysis of fatal intoxication case autopsies was performed at Tongji Center for Medicolegal Expertise in Hubei (TCMEH) from 2009 to 2021 to obtain up-to-date information on intoxication cases. The objective was to describe important data about evolving patterns in intoxication occurrences, enhance public safety policies, and assist forensic examiners and police in more efficient handling of such cases. Analyses based on sex, age, topical exposure routes, toxic agents, and mode of death were performed using 217 records of intoxication cases collected from TCMEH as a sample, and the results were compared with reports previously published (from 1999 to 2008) from this institution. Deaths from intoxications occurred at a higher rate in males than in females and were most common among individuals aged 30-39 years. The most frequent method of exposure was oral ingestion. The causative agents of deadly intoxications have changed when compared to the data from the previous 10 years. For instance, deaths from amphetamine overdoses are becoming more prevalent gradually, whereas deaths due to carbon monoxide and rodenticide intoxication have declined dramatically. In 72 cases, pesticides continued to be the most frequent intoxication cause. A total of 60.4% of the deaths were accidental exposure. Men died from accidents at a higher rate than women, although women were more likely to commit suicide. Particular focus is needed on the use of succinylcholine, cyanide, and paraquat in homicides.

Curcumol inhibits breast cancer growth via NCL/ERα36 and the PI3K/AKT pathway.

Background: Breast cancer (BC) is the most common malignancy worldwide. ERα36 (ERα66 variant) is expressed in many breast cancer cells, especially highly expressed in tamoxifen (TAM)-resistant cell lines and triple-negative breast cancer, and our previous work revealed that nucleolin (NCL) is a protein target of curcumol. This study is aimed at investigating the effect and mechanism of curcumol on ERα36 positive breast cancer cells, and the relationship between curcumol's target protein NCL and ERα36. Study design: Application of in vivo and in vitro studies to reveal the mechanism of curcumol in inhibiting BC growth and the relationship between curcumol's target protein NCL and ERα36. Methods: The anti-tumor effect of curcumol was quantified via an MTT assay, colony formation and cycle arrest, respectively. The expressions of ERα36, NCL and the proteins involved in PI3K/AKT signaling were evaluated by western blotting. The interaction between two proteins was detected using co-immunoprecipitation (Co-IP) and an immunofluorescence assay. A mouse xenograft model was established to verify the role of ERα36 in breast cancer cells and curcumol's effect on ERα36 positive cancer cells. Results: Curcumol inhibited the cell growth, caused cell cycle arrest, decreased cell cycle related proteins and inactivated the PI3K/AKT pathway in ERα36 positive breast cancer cells. There is a positive correlation between NCL and ERα36 in breast cancer cells. In addition, ERα36 bound to NCL; the two proteins were distributed in the nucleus, cytoplasm and plasma membrane, where their expression was obviously decreased by curcumol. Moreover, NCL silenced by NCL siRNA blocked the cell cycle progress and inhibited the activation of PI3K/AKT in MDA-MB-231 cells, while overexpressed ERα36 increased the expression of NCL, promoted the cell cycle progress and enhanced the activity of PI3K/AKT in MCF-7 cells. NCL knockdown or ERα36 overexpression attenuated the effect of curcumol on breast cancer cells. Conclusion: Curcumol reduced the proliferation of breast cancer cells by targeting NCL/ERα36 and inactivating the PI3K/AKT pathway.

Prediction and validation of common targets in atherosclerosis and non-small cell lung cancer influenced by atorvastatin.

BACKGROUND: Cardiovascular disease and cancer are the main causes of morbidity and mortality worldwide. Studies have shown that these two diseases may have some common risk factors. Atorvastatin is mainly used for the treatment of atherosclerosis in clinic. A large number of studies show that atorvastatin may produce anti-tumor activities. This study aimed to predict the common targets of atorvastatin against atherosclerosis and non-small cell lung cancer (NSCLC) based on network pharmacology. METHODS: The target genes of atherosclerosis and NSCLC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The disease-target-component model map and the core network were obtained using Cytoscape 3.7.1. The MTS and wound healing assay were used to detect the effect of atorvastatin on cell viability and migration of A549 cells. The expression of potential common target genes of atorvastatin against atherosclerosis and NSCLC were confirmed in A549 cells and lung cancer tissues of patients. RESULTS: We identified 15 identical pathogenic genes, and four of which (MMP9, MMP12, CD36, and FABP4) were considered as the key target genes of atorvastatin in anti-atherosclerosis and NSCLC. The MTS and wound healing assays revealed that atorvastatin decreased A549 cells migration significantly. Atorvastatin markedly decreased the expression of MMP9, MMP12, CD36, and FABP4 in A549 cells and patients were treated with atorvastatin. CONCLUSIONS: This study demonstrated 15 common pathogenic genes in both atherosclerosis and NSCLC. And verified that MMP 9, MMP 12, CD 36 and FABP 4 might be the common target genes of atorvastatin in anti-atherosclerosis and NSCLC.

Tramadol pretreatment enhances ketamine-induced antidepressant effects and increases mammalian target of rapamycin in rat hippocampus and prefrontal cortex.

Several lines of evidence have demonstrated that acute administration of ketamine elicits fast-acting antidepressant effects. Moreover, tramadol also has potential antidepressant effects. The aim of this study was to investigate the effects of pretreatment with tramadol on ketamine-induced antidepressant activity and was to determine the expression of mammalian target of rapamycin (mTOR) in rat hippocampus and prefrontal cortex. Rats were intraperitoneally administrated with ketamine at the dose of 10 mg/kg or saline 1 h before the second episode of the forced swimming test (FST). Tramadol or saline was intraperitoneally pretreated 30 min before the former administration of ketamine or saline. The locomotor activity and the immobility time of FST were both measured. After that, rats were sacrificed to determine the expression of mTOR in hippocampus and prefrontal cortex. Tramadol at the dose of 5 mg/kg administrated alone did not elicit the antidepressant effects. More importantly, pretreatment with tramadol enhanced the ketamine-induced antidepressant effects and upregulated the expression of mTOR in rat hippocampus and prefrontal cortex. Pretreatment with tramadol enhances the ketamine-induced antidepressant effects, which is associated with the increased expression of mTOR in rat hippocampus and prefrontal cortex.

(1E,4E)-1-(2-Nitro-phen-yl)-5-(2,6,6-trimethyl-cyclo-hex-1-en-1-yl)penta-1,4-dien-3-one.

In the title curcumin-ionone derivative, C(20)H(23)NO(3), the dihedral angle between the cyclo-hexene and benzene rings is 21.03 (8)°, with both double bonds in the inter-linking olefinic chain adopting E conformations. Two of the methyl-ene groups of the ß-ionone ring are disordered over two sets of sites with occupancy ratios of 0.50:0.50 and 0.60:0.40. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds into zigzag chains extending along the b axis.

(1E,4E)-1-(Thio-phen-2-yl)-5-(2,6,6-trimethyl-cyclo-hex-1-en-1-yl)penta-1,4-dien-3-one.

In the title curcumin-ionone derivative, C(18)H(22)OS, the dihedral angle between the thia-zole ring and the mean plane through the cyclo-hexene ring is 5.16 (10)°. The mol-ecule has an E conformation for each of the olefinic bonds.

Computational Analysis Illustrates the Mechanism of Qingfei Paidu Decoction in Blocking the Transition of COVID-19 Patients from Mild to Severe Stage.

BACKGROUND: The epidemic of SARS-CoV-2 has made COVID-19 a serious threat to human health around the world. The severe infections of SARS-CoV-2 are usually accompanied by higher mortality. Although the Qingfei Paidu Decoction (QFPDD) has been proved to be effective in blocking the transition of COVID-19 patients from mild to severe stage, its mechanism remains unclear. OBJECTIVE: This study aims to explore the mechanism of QFPDD in blocking the transition of COVID- 19 patients from mild to severe stage. MATERIALS AND METHODS: In the process of screening active ingredients, oral bioavailability (OB) and drug likeness (DL) are key indicators, which can help to screen out pivotal compounds. Therefore, with the criteria of OB≥30% and DL≥0.18, we searched active ingredients of QFPDD in the Traditional Chinese Medicine Systems Pharmacology (TCMSP, https://tcmspw.com/) by using its 21 herbs as keywords. RESULTS: We filtered out 6 pivotal ingredients from QFPDD by using the bioinformatics method, namely quercetin, luteolin, berberine, hederagenin, shionone and kaempferol, which can inhibit the highly expressed genes (i.e. CXCR4, ICAM1, CXCL8, CXCL10, IL6, IL2, CCL2, IL1B, IL4, IFNG) in severe COVID-19 patients. By performing KEGG enrichment analysis, we found seven pathways, namely TNF signaling pathway, IL-17 signaling pathway, Toll-like receptor signaling pathway, NFkappa B signaling pathway, HIF-1 signaling pathway, JAK-STAT signaling pathway, and Th17 cell differentiation, by which QFPDD could block the transition of COVID-19 patients from mild to severe stage. CONCLUSION: QFPDD can prevent the deterioration of COVID-19 in the following mechanisms, i.e. inhibiting SARS-CoV-2 invasion and replication, anti-inflammatory and immune regulation, and repairing body damage. These results will be helpful for the prevention and treatment of COVID-19.