GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progresses of gastric cancer

Glutamate-ammonia ligase (GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer.

S1P/S1P Receptor Pathway: A New Target for Treatment of Inflammatory Bowel Disease / 胃肠病学

The development of targeted oral drugs that can stably treat inflammatory bowel disease (IBD) is still a clinical problem to be solved. In recent years, studies have confirmed that sphingosine⁃1⁃phosphate (S1P)/S1P receptor pathway can regulate lymphocyte homing and immune regulation, inhibit intestinal inflammation, protect intestinal endothelial barrier, and affect intestinal microbial metabolism, which may play a key role in the treatment of IBD. This article reviewed the effect of S1P/S1P receptor pathway on IBD and its potential mechanism.

Molecular mechanism of Leucopaxillus giganteus against breast cancer based on network pharmacology and in vitro experiments / 中国药理学通报

Aim To study the mechanism of the ethanol extract from Leucopaxillus giganteus (LGEE) in treating breast cancer based on network pharmacology and molecular experimental validation. Methods Some chromatographic methods were used to isolate the chemical constituents of LGEE, and their structures were elucidated based on spectral data. The antitumor activities of LGEE were determined by MTT assay. The predicted targets of LGEE were selected by TCMSP and Pharmmaper, and Genecards database was used to screen the targets. GO and KEGG analysis of target genes were performed. Molecular docking was used to test the binding of active components to core targets. Western blotting was used to validate the regulating function of chlorogenic acid on CHEK2 and CASP3 targets of MDA-MB-231 cells. Results Thirteen compounds were identified including clitocine, chlorogenic acid and so on. LGEE displayed anticancer activities against MDA-MB-231 with the inhibition percent (87. 35 ± 1. 55)%, at the concentration of 200 mg· L

Role and mechanism of DAPT in chronic social defeat stress-induced depressive-like behavior in mice / 中国药理学通报

Aim To investigate the role and mechanism of DAPT in chronic stress-induced depressive-like behavior in mice. Methods C57BL/6J mice were treated with the chronic social defeat stress (CSDS) for 10 days to establish a depression model. Mice in the drug-treated group were injected intraperitoneally with 5 mg • kg

Poisonous substances and geographical distribution of poisoning in hospitalized children based on data from 25 hospitals in China from 2016 to 2020 / 中华儿科杂志

Objective: To investigate the poisonous substances and geographical distribution of poisoning in children in China. Methods: A cross-sectional study. The clinical data of 8 385 hospitalized children from January 2016 to December 2020 were extracted from the FUTang Updating Medical Records database. These children aged 0 to 18 years and were admitted due to poisoning. They were grouped according to age (newborns and infants, toddlers, preschoolers, school-age children, adolescents), place of residence (Northeast China, North China, Central China, East China, South China, Southwest China, Northwest China), and mode of discharge (discharge under medical advice, transfer to another hospital under medical advice, discharge without medical advice, death, other). The poisonous substance and causes of poisoning in different groups were analyzed. Results: Among these 8 385 children, 4 734 (56.5%) were male and 3 651 (43.5%) female, with a male-to-female ratio of 1.3∶1. The age was 3 (2, 7) years. The prevalence of poisoning was 51.8% (4 343/8 385) in toddlers, 16.5% (1 380/8 385) in adolescents, 14.8% (1 242/8 385) in preschoolers, 14.4% (1 206/8 385) in school-age children, and 2.5% (214/8 385) in newborns and infants. Drug poisoning accounted for 43.5% (3 649/8 385) and pesticide accounted for 26.8% (2 249/8 385). Drug poisoning was more common in adolescents (684/1 380, 49.6%) and toddlers (2 041/4 343, 47.0%); non-drug poisoning was more common in school-age children (891/1 206, 73.9%), of which carbon monoxide was mainly in newborns and infants (41/214, 19.2%) and food poisoning in children of school age (241/1 206, 20.0%). Regarding regional characteristics, drug poisoning was more frequent in South China (188/246, 64.2%) and non-drug poisoning was more frequent in Southwest China (815/1 123, 72.5%). For drugs, anti-epileptic drugs, sedative-hypnotic drugs and anti-Parkinson's disease drugs had a higher proportion of poisoning in North China (138/1 034, 13.0%) than that in other regions. For non-drug poisoning, pesticides (375/1 123, 33.3%), food poisoning (209/1 123, 18.6%) and contact with poisonous animals (86/1 123, 7.7%) were more common in Southwest China than in other regions; carbon monoxide poisoning was more common in North China (81/1 034, 7.6%) and Northwest China (65/1 064, 6.3%). In Central China, poisoning happened more in toddlers (792/1 295, 61.2%) and less in adolescents (115/1 295, 8.8%) than in other regions. Regarding different age groups, poisoning in adolescent happened more in Northeast China (121/457, 26.5%), North China (240/1 034, 23.2%), and Northwest China (245/1 064, 23.0%). The rate of discharge under medical advice, discharge without medical advice, and mortality rate within the 5 years were 77.0% (6 458/8 385), 20.8% (1 743/8 385), 0.5% (40/8 385), respectively. Conclusions: Poisoning is more common in male and toddlers. Poisonous substances show a regional characteristic and vary in different age groups, with drugs and insecticides as the most common substances.

Clinical and molecular biological characterization of patients with accelerated chronic lymphocytic leukemia / 中华血液学杂志

Objective: To investigate the clinical and molecular biological characteristics of patients with accelerated chronic lymphocytic leukemia (aCLL) . Methods: From January 2020 to October 2022, the data of 13 patients diagnosed with aCLL at The First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed to explore the clinical and molecular biological characteristics of aCLL. Results: The median age of the patients was 54 (35-72) years. Prior to aCLL, five patients received no treatment for CLL/small lymphocytic lymphoma (SLL), while the other patients received treatment, predominantly with BTK inhibitors. The patients were diagnosed with aCLL through pathological confirmation upon disease progression. Six patients exhibited bulky disease (lesions with a maximum diameter ≥5 cm). Positron emission tomography (PET) -computed tomography (CT) images revealed metabolic heterogeneity, both between and within lesions, and the median maximum standardized uptake value (SUVmax) of the lesion with the most elevated metabolic activity was 6.96 (2.51-11.90). Patients with unmutated IGHV CLL accounted for 76.9% (10/13), and the most frequent genetic and molecular aberrations included +12 [3/7 (42.9% ) ], ATM mutation [6/12 (50% ) ], and NOTCH1 mutation [6/12 (50% ) ]. Twelve patients received subsequent treatment. The overall response rate was 91.7%, and the complete response rate was 58.3%. Five patients experienced disease progression, among which two patients developed Richter transformation. Patients with aCLL with KRAS mutation had worse progression-free survival (7.0 month vs 26.3 months, P=0.015) . Conclusion: Patients with aCLL exhibited a clinically aggressive course, often accompanied by unfavorable prognostic factors, including unmutated IGHV, +12, ATM mutation, and NOTCH1 mutation. Patients with CLL/SLL with clinical suspicion of disease progression, especially those with bulky disease and PET-CT SUVmax ≥5, should undergo biopsy at the site of highest metabolic uptake to establish a definitive pathological diagnosis.

Validation of the prognostic value of the Mayo MASS and R2-ISS staging systems in patients newly diagnosed with multiple myeloma: A single-center study / 中华血液学杂志

Objective: To evaluate the prognostic value of Mayo MASS and R2-ISS staging systems in patients newly diagnosed with multiple myeloma (MM) . Methods: A total of 371 patients newly diagnosed with MM in Jiangsu Province Hospital were included in the study. Cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization (cIg-FISH) was performed to detect cytogenetic abnormality. Clinical characteristics were combined to analyze the disease stage and evaluate the prognosis. Results: There were 37 (10.0%), 264 (71.0%), and 70 (18.8%) patients in R-ISS stage Ⅰ, Ⅱ, and Ⅲ, respectively. The median progression-free survival (PFS) times were 37, 25, and 14 months (P<0.001). The median overall survival (OS) times were not reached (NR), 66, and 30 months (P<0.001). There were 71 (19.1%), 140 (37.7%), and 160 (43.2%) patients in Mayo MASS stages Ⅰ, Ⅱ, and Ⅲ, and the median PFS times periods were 43, 27, and 19 months (P<0.001), and the median OS times were NR, NR, 35 months, respectively (P<0.001). There were, 23 (6.2%), 69 (18.6%), 222 (59.8%), and 57 (15.4%) patients in R2-ISS stages Ⅰ, Ⅱ, Ⅲ, and Ⅳ, respectively. The median PFS times were 47, 31, 25, and 15 months (P=0.001), and the median OS times were NR, NR, 49, and 55 months, respectively (P<0.001) . Conclusion: Based on the R-ISS staging system, Mayo MASS, and R2-ISS prognostic staging system incorporated 1q21+, which allows a better stratification. However, the proportion of stage Ⅲ patients in Mayo MASS and R2-ISS staging systems is relatively high, which is considered related to the high incidence of 1q21+ and ISS Ⅲ in the Chinese population.

Enzyme production mechanism of anaerobic fungus Orpinomyces sp. YF3 in yak rumen induced by different carbon source / 生物工程学报

In order to investigate the enzyme production mechanism of yak rumen-derived anaerobic fungus Orpinomyces sp. YF3 under the induction of different carbon sources, anaerobic culture tubes were used for in vitro fermentation. 8 g/L of glucose (Glu), filter paper (Flp) and avicel (Avi) were respectively added to 10 mL of basic culture medium as the sole carbon source. The activity of fiber-degrading enzyme and the concentration of volatile fatty acid in the fermentation liquid were detected, and the enzyme producing mechanism of Orpinomyces sp. YF3 was explored by transcriptomics. It was found that, in glucose-induced fermentation solution, the activities of carboxymethyl cellulase, microcrystalline cellulase, filter paper enzyme, xylanase and the proportion of acetate were significantly increased (P < 0.05), the proportion of propionate, butyrate, isobutyrate were significantly decreased (P < 0.05). The results of transcriptome analysis showed that there were 5 949 differentially expressed genes (DEGs) between the Glu group and the Flp group, 10 970 DEGs between the Glu group and the Avi group, and 6 057 DEGs between the Flp group and the Avi group. It was found that the DEGs associated with fiber degrading enzymes were significantly up-regulated in the Glu group. Gene ontology (GO) function enrichment analysis identified that DEGs were mainly associated with the xylan catabolic process, hemicellulose metabolic process, β-glucan metabolic process, cellulase activity, endo-1,4-β-xylanase activity, cell wall polysaccharide metabolic process, carbohydrate catabolic process, glucan catabolic process and carbohydrate metabolic process. Moreover, the differentially expressed pathways associated with fiber degrading enzymes enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were mainly starch and sucrose metabolic pathways and other glycan degradation pathways. In conclusion, Orpinomyces sp. YF3 with glucose as carbon source substrate significantly increased the activity of cellulose degrading enzyme and the proportion of acetate, decreased the proportion of propionate, butyrate and isobutyrate. Furthermore, the degradation ability and energy utilization efficiency of fungus in the presence of glucose were improved by means of regulating the expression of cellulose degrading enzyme gene and participating in starch and sucrose metabolism pathway, and other glycan degradation pathways, which provides a theoretical basis for the application of Orpinomyces sp. YF3 in practical production and facilitates the application of Orpinomyces sp. YF3 in the future.

Comprehensive Diagnosis of Mantle Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To explore the value of multiple detection methods based on histopathology and supplemented by bone marrow or peripheral blood sample detections in the comprehensive diagnosis of mantle cell lymphoma (MCL).@*METHODS@#The clinical, immunophenotypic, pathologic, cytogenetic and molecular features of 153 newly diagnosed MCL patients admitted to the hematology department of our hospital from May 2009 to September 2022 were analyzed.@*RESULTS@#144 (96.6%) of the 149 MCL patients who underwent marrow or peripheral blood IGH/CCND1 FISH detection at initial diagnosis were positive, of which 36 cases (24.2%) had a low proportion positive. The immunophenotypes in 115 patients were analyzed by flow cytometry (FCM), 89 cases (77.4%) conformed to MCL while 23 cases (20.0%) were initially diagnosed as B-cell lymphoproliferative disorders (B-LPD). Of the 75 cases who performed bone marrow biopsy, 50 cases (66.7%) had morphological and immunophenotypic characteristics consistent with MCL, 15 cases (20.0%) were classified as B-LPD, and 10 cases with no obvious abnormality. 77 patients underwent histopathology examination, of which 73 cases (94.8%) had typical clinicopathological features of MCL, including 2 CCND1 negative MCL, 2 pleomorphic variants, 5 pleomorphic variants and 4 cases diagnosed as other leukemia or lymphoma. Among 153 cases of MCL, 128 cases were classic MCL(cMCL), and another 25 cases (16.3%) were diagnosed as leukemic non-lymph node MCL (lnnMCL). The incidence of IGHV mutation, TP53 mutation and CD23 expression positive were significantly different between cMCL and lnnMCL.@*CONCLUSION@#Histopathology is still the main standard for the diagnosis of cMCL, and detection based on bone marrow or peripheral blood samples is an important means for the diagnosis of lnnMCL. Single marker or examination can cause a certain proportion of misdiagnosis. The accurate diagnosis of MCL depends on a combination of multiple detection methods.

The Expression Level and Diagnostic Value of Serum Free Light Chain in B-Cell Non-Hodgkin Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression level and the diagnostic value of serum free light chain in B-cell non-Hodgkin's lymphoma (B-NHL).@*METHODS@#We retrospectively analyzed the results of serum free light chain (sFLC) of 394 newly treated B-NHL patients in our hospital from January 2014 to December 2021 and compared the secretion levels of sFLC among different subtypes of B-NHL. The value of sFLC secretion levels in the diagnosis of WM was evaluated using ROC.@*RESULTS@#Increased proportion of sFLC, abnormal ratio of sFLC (κ / λ) and the secretion levels of sFLC (κ+λ) were different in different B-NHL subtypes, Waldenstrom's macroglobulinemia (WM) had the highest proportion of elevated sFLC(82.68%) and abnormal sFLC(κ/ λ)(87.0%), the proportion of FL(18.0%) and DLBCL patients(12.8%) with elevated sFLC was lower (P<0.05). The expression levels of sFLC can helpful in the diagnosis of WM (AUC=0.874，P<0.001， 95% CI: 0.779-0.970). At the same time, higher sFLC levels and sFLC cloning patterns predicted the possibility of bone marrow infiltration of lymphoma.@*CONCLUSION@#The serum free light chains is common in patients with B-NHL. The elevated level and type of free light chain are associated with the type of lymphoma, and the patients with bone marrow infiltration have higher sFLC（κ+ λ） expression level.

Arthroscopic treatment of scaphoid fracture nonunion with bone graft and Kirschner wire combined with screw fixation / 中国修复重建外科杂志

OBJECTIVE@#To explore the effectiveness of arthroscopic treatment of scaphoid fracture nonunion with bone graft and Kirschner wire combined with screw fixation.@*METHODS@#The clinical data of 14 patients with scaphoid fracture nonunion who met the selection criteria between February 2021 and September 2022 were retrospectively analyzed. There were 13 males and 1 female with an average age of 32 years ranging from 17 to 54 years. The time from injury to operation ranged from 6 to 15 months, with an average of 9.6 months. According to the Slade-Geissler classification of scaphoid fracture nonunion, there were 3 cases of grade Ⅲ, 8 cases of grade Ⅳ, and 3 cases of grade Ⅴ. The preoperative visual analogue scale (VAS) score was 5.9±1.0, and the modified Mayo wrist score was 53.2±9.1. There were 2 cases of scaphoid nonunion advanced collapse, both of which were stage Ⅰ. All patients were treated with arthroscopic bone graft and Kirschner wire combined with screw fixation, and the fracture healing was observed by X-ray film monthly after operation, and the effectiveness was evaluated by VAS score and modified Mayo wrist score before and after operation.@*RESULTS@#All patients were followed up 6-14 months, with an average of 8.4 months. All fractures healed in 4-8 months, with an average of 6.3 months. The postoperative pain symptoms and wrist function of the patients significantly improved when compared with those before operation, and the VAS score at last follow-up was 2.4±1.3, and the modified Mayo wrist score was 87.1±6.7, which were significantly different from those before operation ( t=12.851, P<0.001; t=-14.410, P<0.001). According to the modified Mayo wrist evaluation, 9 cases were excellent, 3 cases were good, and 2 cases were fair.@*CONCLUSION@#Arthroscopic bone graft and Kirschner wire combined with screw fixation is an effective surgical method for the treatment of scaphoid fracture nonunion.

Aucubin combined with ADSCs-exos protects TBHP-induced nucleus pulposus cells via TLR4/NF-κB pathway / 中国中药杂志

This paper aims to investigate the effects and mechanisms of adipose-derived stem cells-exosomes(ADSCs-exos) toge-ther with aucubin in protecting human-derived nucleus pulposus cells(NPCs) from inflammatory injury, senescence, and apoptosis. The tert-butyl hydroperoxide(TBHP)-induced NPCs were assigned into normal, model, aucubin, ADSCs-exos, and aucubin+ADSCs-exos groups. The cell viability was examined by cell counting kit-8(CCK-8), cell proliferation by EdU staining, cell senescence by senescence-associated-β-galactosidase(SA-β-Gal), and cell cycle and apoptosis by flow cytometry. Enzyme-linked immunosorbent assay was employed to examine the expression of interleukin-1β(IL-1β), IL-10, and tumor necrosis factor-α(TNF-α). Real-time fluorescence quantitative PCR and Western blot were employed to determine the mRNA and protein levels of aggregated proteoglycan(aggrecan), type Ⅱ collagen alpha 1(COL2A1), Toll-like receptor 4(TLR4), and nuclear factor-kappa B(NF-κB). The results showed that compared with the model group, the aucubin or ADSCs-exos group showed enhanced viability and proliferation of NPCs, decreased proportion of G_0/G_1 phase cells, increased proportion of S phase cells, reduced apoptosis and proportion of cells in senescence, lowered IL-1β and TNF-α levels, elevated IL-10 level, down-regulated mRNA and protein levels of TLR4 and NF-κB, and up-regulated mRNA and protein levels of aggrecan and COL2A1. Compared with the aucubin or ADSCs-exos group, the aucubin+ADSCs-exos combination further increased the viability and proliferation of NPCs, decreased the proportion of G_0/G_1 phase cells, increased the proportion of S phase cells, reduced the apoptosis and proportion of cells in senescence, lowered the IL-1β and TNF-α levels, elevated the IL-10 level, down-regulated the mRNA and protein levels of TLR4 and NF-κB, and up-regulated the mRNA and protein levels of aggrecan and COL2A1. In summary, both aucubin and ADSCs-exos could exert protective effects by inhibiting inflammatory responses, reducing apoptosis and senescence of NPCs, improving cell viability and proliferation as well as extracellular matrix synthesis, which may be associated with the inhibition of TLR4/NF-κB signaling pathway activation. The combination of both plays a synergistic role in the protective effects.

Comparative study of purgative pharmacological effects and mechanisms of Moringa oleifera leaves and Rhei Radix et Rhizoma / 中国中药杂志

Moringa oleifera leaves are known for their "Virechana"(purgative) effect in Ayurvedic medicine in India. This study compared the purgative effects and mechanisms of M. oleifera leaves with the reference Rhei Radix et Rhizoma to establish a foundation for the further application of M. oleifera leaves in traditional Chinese medicine(TCM). Using network pharmacology and molecular docking methods, this study identified the material basis, common targets, and signaling pathways through which Rhei Radix et Rhizoma and M. oleifera leaves exerted their purgative pharmacological effects. A low-fiber diet-induced constipation mouse model was established to measure fecal parameters and small intestinal propulsion rate, and histological changes in the colon were observed using HE staining. Relative expression levels of relevant genes and target proteins were assessed using RT-qPCR and immunohistochemistry, respectively. The results showed that mapping the targets of Rhei Radix et Rhizoma and M. oleifera leaves onto the biological process network of constipation revealed close proximity, indicating that they may exert their therapeutic effects on constipation through similar biological processes. Molecular docking results indicated that compounds such as sennoside C and isoquercitrin could target serine/threonine protein kinases(AKT1) and mitogen-activated protein kinase 3(MAPK3), thereby affecting MAPK and calcium signaling pathways to promote defecation. Animal experiments demonstrated that both M. oleifera leaves and Rhei Radix et Rhizoma increased the number of fecal pellets and water content in constipated mice, improved small intestine motility, colon mucosal thickness, and muscle layer thickness, upregulated the gene expression levels of AKT1 and MAPK3 in the colon, and downregulated the expression of AQP3 protein. These findings suggest that M. oleifera leaves and Rhei Radix et Rhizoma share similarities in their therapeutic efficacy and mechanisms for treating constipation. Using Rhei Radix et Rhizoma as a reference can provide a better understanding of the characteristics of the "Virechana"(purgative) effect of M. oleifera leaves in TCM.

Research progress in pathogenesis and traditional Chinese medicines treatment of ischemic stroke-related headache / 中国中药杂志

Headache is a common clinical complication of ischemic stroke. As a precursor of stroke, headache occurs repeatedly in the convalescent period of ischemic stroke, leading to secondary stroke and seriously hindering patients' rehabilitation. Currently, it is believed that the pathogenesis of ischemic stroke-related headache is associated with the abnormal release of vasoactive substances, high platelet aggregation, and stimulation of intracranial pain-sensitive structures. The active ingredients in traditional Chinese medicines(TCM) with the effects of activating blood to resolve stasis and clearing heat to release exterior can protect brain tissue and relieve headache by reducing the release of inflammatory cytokines, alleviating antioxidant stress, inhibiting neuronal apoptosis and so on. This paper introduces the research progress in the potential mechanism and TCM treatment of ischemic stroke-related headache, aiming to provide reference for further research and drug development of this complication.

Effects of Xihuang Pills on proliferation and apoptosis of prostate cancer LNCaP cells based on AR/m TOR signaling pathway / 中国中药杂志

Based on the androgen receptor(AR)/mammalian target of rapamycin(mTOR)signaling pathway, the effects of Xihuang Pills-medicated serum on the proliferation and apoptosis of prostate cancer LNCaP cells were investigated. The drug-containing serum of SD rats was prepared by intragastric administration of Xihuang Pills suspension. The effects of low-, medium-, and high-dose Xihuang Pills-containing serum on the in vitro proliferation of LNCaP cells were detected by cell counting kit-8(CCK-8). Flow cytometry was used to detect the apoptosis level of LNCaP cells after intervention with different concentrations of Xihuang Pills. Protein expression of cleaved cysteinyl aspartate-specific proteinase caspase-3(cleaved caspase-3), B-cell lymphoma-2(Bcl-2), and AR as well as the phosphorylation level of mTOR protein were detected by Western blot. The results showed that compared with the blank serum, the drug-medicated serum could blunt the activity of LNCaP cells. Low-, medium-, and high-dose Xihuang Pills-containing serum could significantly increase the cell apoptosis rate, increase the expression of cleaved caspase-3 protein, decrease the expression of Bcl-2 protein, reduce the expression of AR protein, and down-regulate the level of phosphorylated mTOR(p-mTOR). To study the effect of Xihuang Pills on the growth of LNCaP cells in vivo, different doses of Xihuang Pills were used to intervene in the subcutaneous graft model in nude mice inoculated with LNCaP cells. The expression levels of AR, mTOR, p-mTOR, Bcl-2, and cleaved caspase-3 were detected by Western blot. The results showed that the volumes of subcutaneous graft tumor in the low-dose, medium-dose, and high-dose Xihuang Pills groups significantly decreased compared with that in the model group. The weight of subcutaneous transplanted tumor in each group with drug intervention was significantly lower than that in the model group. Compared with the model group, the low-dose, medium-dose, and high-dose Xihuang Pills groups showed increased cleaved caspase-3 protein expression, decreased Bcl-2 and AR protein expression, and reduced p-mTOR protein expression. Further experiments showed that AR agonist R1881 could block the anti-proliferation and pro-apoptotic effects of Xihuang Pills. The mechanism of Xihuang Pills against prostate cancer is related to the inhibition of the AR/mTOR signaling pathway, inhibition of LNCaP cell proliferation, and induction of apoptosis in cancer cells.

Effects of FasL inhibitors on corneal apoptosis and Treg after corneal transplantation in rats / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To explore the effect of intravitreal injection FasL inhibitors on corneal apoptosis, Fas, FasL expression, Treg numbers in blood and lymph nodes and rejection index in rats after corneal transplantation.METHODS:A total of 24 SD rats(24 eyes)who received penetrating keratoplasty were randomly divided into two groups: PBS group received intravitreal injection of PBS(12 rats, 12 eyes)and FasL inhibitor group(12 rats, 12 eyes). Rejection index was recorded every week and blood samples and lymph node were collected at 1, 3 and 5wk after surgery to analyze the proportions of Treg. Corneal tissue was collected for detecting the expression of Fas and FasL and number of apoptosis.RESULTS: The expression of Fas, FasL in FasL inhibitor group decreased significantly compared with the PBS group(all P&#x003C;0.05); Corneal cell apoptosis significantly decreased in FasL inhibitor group, and it was the lowest at 5wk after surgery; Treg numbers in blood and lymph nodes significantly increased in FasL inhibitor group at 3wk after surgery(all P&#x003C;0.05); rejection index of corneal transplantation in the FasL inhibitor group was significantly lower than that of PBS group(all P&#x003C;0.05).CONCLUSION:Intravitreal injection of FasL inhibitors after corneal transplantation could reduce the apoptosis in all layers of cornea, increase the number of Tregs in blood and lymph nodes, and alleviate rejection.

Sleep status and influencing factors among higher vocational college students / 四川精神卫生

BackgroundSleep disorder can adversely affect human physical and mental health， with important implications for socioeconomic development. And higher vocational college students are subject to various pressures and stimuli exerted by academic studies， job seeking and family socioeconomic status， which may contribute to the onset insomnia symptom or sleep disorder. ObjectiveTo discuss the sleep status and influencing factors among higher vocational college students， and to provide references for improving their sleep status. MethodsIn January and February， 2022， a stratified random sampling method was utilized to enroll 3 300 students from five higher vocational colleges in Wenjiang district of Chengdu city. All the participants were assessed using Insomnia Severity Index （ISI）， Patient Health Questionnaire Depression Scale-9 item （PHQ-9） and Generalized Anxiety Disorder Scale-7 （GAD-7）. Pearson correlation analysis was conducted to test the correlation of ISI with PHQ-9 and GAD-7 scores， and the Logistic regression analysis was performed to identify the influencing factors of insomnia symptom in higher vocational college students. ResultInsomnia symptom was detected in 81.90% （2 497 / 3 300） of higher vocational college students. The detection rate of insomnia symptom among vocational college students yielded statistical difference in terms of gender， family socioeconomic status， being an only child or having siblings， degree of psychological pressure exerted by academic studies or job seeking， amount of hours spent on Internet per day， frequency of physical exercise， and the presence or absence of anxiety symptom and depression symptom （χ2=21.032， 22.172， 8.983， 75.939， 36.781， 32.350， 54.512， 86.561， P<0.01 or 0.05）. Among higher vocational college students， ISI score was positively correlated with GAD-7 and PHQ-9 scores （r=0.620， 0.714， P<0.01）， and GAD-7 score was positively correlated with PHQ-9 score （r=0.824， P<0.01）. Gender， family socioeconomic status， degree of psychological pressure exerted by academic studies or job seeking， amount of hours spent on Internet per day， frequency of physical exercise， and the presence or absence of anxiety symptom and depression symptom were effective factors in predicting the insomnia symptom in higher vocational college students （P<0.01 or 0.05）. ConclusionFemale gender， average and below average family socioeconomic status， moderate-to-severe degree of psychological pressure exerted by academic studies or job seeking， spending 2~5 h， 5~7 h or >7 h on Internet per day， inadequate physical exercise and presence of depressive symptom are the risk factors for insomnia symptom in higher vocational college students.［Funded by Sichuan Provincial Primary Health Development Research Center in 2022， North Sichuan Medical College （number， SWFZ22-C-89）］

Electromyographic signals and the starting threshold voltage of orbicularis oris muscle in healthy rhesus monkeys / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the characteristics of electromyography (EMG) signals and the starting threshold voltages of the orbicularis oris muscles (OOM) in healthy rhesus monkeys under different muscle movement conditions. Methods: The EMG signals and the starting threshold voltages at different time points in 4 healthy rhesus monkeys were acquired and recorded with EMG device and evoked potentiometer. The voltage amplitude variation of EMG signals was analyzed, and the voltage amplitude range of EMG signals at the beginning of OOM contraction was established. The data were statistically analyzed by one-way ANOVA. Results: The EMG of OOM in healthy monkeys in the quiet, natural and continuous mouth-closed state was linear and relatively stable, and the absolute value fluctuated between 15 and 50 μV. The EMG waveform increased rapidly during the natural lip contraction movement, and its amplitude fluctuated greatly, with the highest absolute value of the peak value reaching hundreds of microvolts. The amplitude of EMG induced by continuous mouth closure was more than thousands of microvolts. There was no significant difference in EMG amplitudes of OOM in the healthy rhesus monkey under quiet and continuous lip closure at different time points (P>0.05). There was no significant difference in threshold voltages in the state of natural lip contraction of bilateral OOM at different time points (average range: 57.17-57.47 μV) in the healthy rhesus monkeys (P>0.05). There was no significant difference in threshold voltages of OOM induced by bilateral OOM at different time points(average range: 55.38-55.99 μV) in the healthy rhesus monkeys(P>0.05). There were significant differences in the absolute values of EMG amplitudes of OOM between the three lip movement modes: (30.67±8.72) μV in quiet and natural continuous lip closure (475.12±54.72) μV in natural lip contraction, and (921.22±312.79) μV in the induced persistent lip closure, with t values of -8.48, -9.35 and -5.01 respectively, all P<0.001. Conclusions: The EMG signals of OOM show different characteristics under different muscle movement conditions, which can be used as a basis for computer to judge and recognize the movement conditions of OOM. The upper limits of the EMG threshold voltage values of OOM under different motion states are 55-60 μV.

Advances of immunotherapy-related biomarker in esophageal carcinoma / 中华胃肠外科杂志

Esophageal carcinoma is one of the most common malignant tumors in the world, with incidence and mortality rankings of 7th and 6th, respectively. In recent years, immunotherapy represented by immune checkpoint inhibitors of programmed death-1 and programmed death ligand 1 (PD-L1) has been introduced into clinical practice and has changed the treatment status of esophageal cancer. Although immunotherapy has provided long-term survival benefits for patients with advanced esophageal cancer and high pathological response rates in the neoadjuvant therapy, only a few of the patients have satisfactory therapeutic outcomes. Therefore, effective biomarkers for predicting immunotherapeutic effects are urgently needed to identify those patients who could benefit from immunotherapy. In this paper, we mainly discuss recent research advances of biomarkers related to the immunotherapy of esophageal cancer and the clinical application prospects of these biomarkers.

Flavonoid glycosides from the water extract of Artemisia annua L / 药学学报

Twenty one flavonoid glycosides were isolated and purified from n-butanol portion of the water extract of A. annua by various chromatographic techniques such as HP-20 macroporous adsorption resin, silica gel, ODS, Sephadex LH-20 gel column chromatography and preparative high performance liquid chromatography. Their structures were identified by analysis of physicochemical properties and spectral data, and determined as axillarin-7-O-β-D-xylopyranosyl-(1→6)-β-D-glucopyranoside (1), orientin (2), apigenin-6-C-β-D-glucopyranosyl-8-C-β-L-arabinopyranoside (3), apigenin-6-C-β-D-galactopyranosyl-8-C-β-L-arabinopyranoside (4), apigenin-6-C-β-L-arabinopyranosyl-8-C-β-D-glucopyranoside (5), apigenin-6-C-α-L-arabinofuranosyl-8-C-β-D-glucopyranoside (6), quercetin-3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranoside (7), apigenin-6-C-α-L-arabinopyranosyl-8-C-β-D-glucopyranoside (8), vicenin-2 (9), patuletin-7-O-β-D-glucopyranoside (10), luteolin-6-C-glucopyranoside (11), vitexin (12), kaempferol-3-O-β-galactopyranosyl-(1→2)-β-glucopyranoside (13), quercetin-7-O-β-D-glucopyranoside (14), patuletin-3-O-β-D-glucopyranoside (15), 7-O-methyl-quercetagetin-6-O-β-D-glucopyranoside (16), quercetin-3-O-β-D-glucopyranoside (17), nepitrin (18), rutin (19), kaempferol-3-O-β-sophoroside (20), and patuletin-3-O-rutinoside (21). Compound 1 is a new compound, compounds 2, 4, 6, 7, 10, 11, 13, 15, 16, 18, 20 and 21 are isolated from A. annua for the first time. In the anti-inflammatory assay, compound 1 inhibited the release of IL-6 from LPS-induced RAW264.7 cells to significantly degrees with the high (100 μmol·L-1), medium (50 μmol·L-1), low (25 μmol·L-1) concentration.