NnWOX1-1, NnWOX4-3, and NnWOX5-1 of lotus (Nelumbo nucifera Gaertn)promote root formation and enhance stress tolerance in transgenic Arabidopsis thaliana.

BACKGROUND: Adventitious roots (ARs) represent an important organ system for water and nutrient uptake in lotus plants because of degeneration of the principal root. The WUSCHEL-related homeobox (WOX) gene regulates plant development and growth by affecting the expression of several other genes. In this study, three WOX genes, NnWOX1-1, NnWOX4-3, and NnWOX5-1, were isolated and their functions were assessed in Arabidopsis plants. RESULTS: The full lengths of NnWOX1-1, NnWOX4-3, and NnWOX5-1 were 1038, 645, and 558 bp, encoding 362, 214, and 185 amino acid residues, respectively. Phylogenetic analysis classified NnWOX1-1 and NnWOX4-3 encoding proteins into one group, and NnWOX5-1 and MnWOX5 encoding proteins exhibited strong genetic relationships. The three genes were induced by sucrose and indoleacetic acid (IAA) and exhibited organ-specific expression characteristics. In addition to improving root growth and salt tolerance, NnWOX1-1 and NnWOX4-3 promoted stem development in transgenic Arabidopsis plants. A total of 751, 594, and 541 genes, including 19, 19, and 13 respective genes related to ethylene and IAA metabolism and responses, were enhanced in NnWOX1-1, NnWOX4-3, and NnWOX5-1 transgenic plants, respectively. Further analysis showed that ethylene production rates in transgenic plants increased, whereas IAA, peroxidase, and lignin content did not significantly change. Exogenous application of ethephon on lotus seedlings promoted AR formation and dramatically increased the fresh and dry weights of the plants. CONCLUSIONS: NnWOX1-1, NnWOX4-3, and NnWOX5-1 influence root formation, stem development, and stress adaptation in transgenic Arabidopsis plants by affecting the transcription of multiple genes. Among these, changes in gene expression involving ethylene metabolism and responses likely critically affect the development of Arabidopsis plants. In addition, ethylene may represent an important factor affecting AR formation in lotus seedlings.

Untargeted LC-QTOF-MS/MS-based metabolomics of spent coffee grounds alcoholic beverages fermented with Lachancea thermotolerans and Lactiplantibacillus plantarum.

Spent coffee grounds (SCG) is a solid waste generated from coffee brewing. We recently developed a novel SCG hydrolysate-derived alcoholic beverage fermented with Lachancea thermotolerans Concerto and Lactiplantibacillus plantarum ML Prime. To further understand the potential health benefits of the fermented SCG hydrolysate alcoholic beverage, an untargeted metabolomics-based approach (UPLC-QTOF-MS/MS) was applied to detect and identify bioactive metabolites especially low molecular weight compounds. Our results showed that, compared to yeast monoculture-fermented SCG alcoholic beverages, yeast-lactic acid bacterial coculture enriched the beverage with a range of bioactive compounds especially aromatic and branched-chain amino acid derivatives (e.g., 4-hydroxyphenyl lactic acid, phenyl lactic acid, indole lactic acid, (S)-(-)-2-hydroxyisocaproic acid, and 4-hydroxyphenyl ethanol). Although some endogenous phenolic compounds were metabolized during fermentation, many phenolic metabolites (e.g., vinyl phenols, dihydrocaffeic acid, 3,4-dihydroxybenzoic acid, 4-hydroxycoumarin) were produced. Our study provided a theoretical basis for further valorization of SCG hydrolysates from the health benefits point of view and the findings may be extended to other fermented products.

Role of the heat shock protein family in chlorpromazine-induced cardiotoxicity.

Chlorpromazine (CPZ), a first-generation antipsychotic, is widely used in treating schizophrenia and other psychiatric disorders. However, CPZ is also associated with an increased likelihood of sudden cardiac death, and the underlying mechanisms remain unclear. In our study, we aimed to determine the CPZ-induced changes in some members of the heat shock protein family in rat hearts and further explore the possible mechanisms of CPZ-induced cardiotoxicity. Twenty-four Sprague Dawley rats were randomly divided into three groups (n = 8 per group): control, low dose (33.216 mg/kg) and high dose (94.211 mg/kg). CPZ administration induced hypothermia in rats. Pathological changes, including ischaemia and hypoxia, were observed in rat hearts. Furthermore, the serum levels of cardiac Troponin T (c-TN-T) and brain natriuretic peptide (BNP) were elevated in the CPZ-exposed groups. Meanwhile, the protein and gene expression of HSP70, HSP60, HSP27 and HSP10 significantly differed between the CPZ-exposed and control groups. We conclude that acute CPZ exposure could lead to myocardial injury in rats, in which HSPs might play a crucial role. Further investigations are required to elucidate the underlying mechanisms.

Effect of macronutrient fertilization on olive oil composition and quality under irrigated, intensive cultivation management.

BACKGROUND: Intensive olive (Olea europaea L.) orchards are fertilized, mostly with the macronutrients nitrogen (N), phosphorus (P) and potassium (K). The effects of different application levels of these nutrients on olive oil composition and quality were studied over 6 years in a commercial intensively cultivated 'Barnea' olive orchard in Israel. RESULTS: Oil quality and composition were affected by N, but not P or K availability. Elevated N levels increased free fatty acid content and reduced polyphenol level in the oil. Peroxide value was not affected by N, P or K levels. The relative concentrations of palmitoleic, linoleic and linolenic fatty acids increased with increasing levels of N application, whereas that of oleic acid, monounsaturated-to-polyunsaturated fatty acid ratio and oleic-to-linoleic ratio decreased. CONCLUSION: These results indicate that intensive olive orchard fertilization should be carried out carefully, especially where N application is concerned, to avoid a decrease in oil quality due to over-fertilization. Informed application of macronutrients requires leaf and fruit analyses to establish good agricultural practices, especially in view of the expansion of olive cultivation to new agricultural regions and soils. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Regulatory Mechanism of Mangiferin Combined with Bortezomib on Malignant Biological Behavior of Burkitt Lymphoma and Its Effect on Expression of CXC Chemokine Receptors / 中国实验血液学杂志

OBJECTIVE@#To analyze the effects of mangiferin combined with bortezomib on the proliferation, invasion, apoptosis and autophagy of human Burkitt lymphoma Raji cells, as well as the expression of CXC chemokine receptors (CXCRs) family, and explore the molecular mechanism between them to provide scientific basis for basic research and clinical work of Burkitt lymphoma.@*METHODS@#Raji cells were intervened with different concentrations of mangiferin and bortezomib alone or in combination, then cell proliferation was detected by CCK-8 assay, cell invasion ability was detected by Transwell chamber method, cell apoptosis was detected by Annexin V/PI double-staining flow cytometry, apoptosis, autophagy and Akt/mTOR pathway protein expression were detected by Western blot, and the expression changes of CXCR family was detected by real-time quantitative PCR (RT-qPCR).@*RESULTS@#Different concentrations of mangiferin intervened Raji cells for different time could inhibit cell viability in a concentration- and time-dependent manner (r =-0.682, r =-0.836). When Raji cells were intervened by combination of mangiferin and bortezomib, compared with single drug group, the proliferation and invasion abilities were significantly decreased, while the apoptosis level was significantly increased (P <0.01). Mangiferin combined with bortezomib could significantly up-regulate the expression of pro-apoptotic protein Bax and down-regulate the expression of anti-apoptotic protein Bcl-2 after intervention in Raji cells. Caspase-3 was also hydrolyzed and activated, and then induced the apoptosis of Raji cells. Mangiferin combined with bortezomib could up-regulate the expression of LC3Ⅱ protein in Raji cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P <0.01). Mangiferin combined with bortezomib could significantly inhibit the phosphorylation levels of Akt and mTOR, inhibit the proliferation and invasion of Raji cells by inhibiting Akt/mTOR pathway, and induce cell autophagy and apoptosis. Mangiferin and bortezomib could down-regulate the expressions of CXCR4 and CXCR7 mRNA after single-agent intervention in Raji cells, and the down-regulations of CXCR4 and CXCR7 mRNA expression were more significant when the two drugs were combined (P <0.01). Mangiferin alone or combined with bortezomib had no significant effect on CXCR5 mRNA expression in Raji cells (P >0.05), while the combination of the two drugs could down-regulate the expression of CXCR3 (P <0.05).@*CONCLUSION@#Mangiferin combined with bortezomib can synergistically inhibit the proliferation and invasion of Raji cells, and induce autophagy and apoptosis. The mechanism may be related to the inhibition of Akt/mTOR signaling pathway, down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic protein Bax, and the inhibition of the expression of CXCR family.

EPCs-exos combined with tanshinone Ⅱ_A protect vascular endothelium cells from oxidative damage via PI3K/Akt pathway / 中国中药杂志

This study aims to investigate the molecular mechanism of tanshinone Ⅱ_(A )(TaⅡ_A) combined with endothelial progenitor cells-derived exosomes(EPCs-exos) in protecting the aortic vascular endothelial cells(AVECs) from oxidative damage via the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt) pathway. The AVECs induced by 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphocholine(POVPC) were randomly divided into model, TaⅡ_A, EPCs-exos, and TaⅡ_A+EPCs-exos groups, and the normal cells were taken as the control group. The cell counting kit-8(CCK-8) was used to examine the cell proliferation. The lactate dehydrogenase(LDH) cytotoxicity assay kit, Matrigel assay, DCFH-DA fluorescent probe, and laser confocal microscopy were employed to examine the LDH release, tube-forming ability, cellular reactive oxygen species(ROS) level, and endothelial cell skeleton morphology, respectively. The enzyme-linked immunosorbent assay was employed to measure the expression of interleukin(IL)-1β, IL-6, and tumor necrosis factor(TNF)-α. Real-time fluorescence quantitative PCR(qRT-PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of PI3K and Akt. Compared with the control group, the model group showed decreased cell proliferation and tube-forming ability, increased LDH release, elevated ROS level, obvious cytoskeletal disruption, increased expression of IL-1β, IL-6, and TNF-α, and down-regulated mRNA and protein levels of PI3K and Akt. Compared with the model group, TaⅡ_A or EPCs-exos alone increased the cell proliferation and tube-forming ability, reduced LDH release, lowered the ROS level, repaired the damaged skeleton, decreased the expression of IL-1β, IL-6, and TNF-α, and up-regulated the mRNA and protein levels of PI3K and Akt. TaⅡ_A+EPCs-exos outperformed TaⅡ_A or EPCs-exos alone in regulating the above indexes. The results demonstrated that TaⅡ_A and EPCs-exos exerted a protective effect on POVPC-induced AVECs by activating the PI3K/Akt pathway, and the combination of the two had stronger therapeutic effect.

Systematic review and Meta-analysis of efficacy and safety of Shufeng Jiedu Capsules in treatment of influenza / 中国中药杂志

This study aims to systematically review the efficacy and safety of Shufeng Jiedu Capsules in the treatment of influenza. The randomized controlled trial(RCT) of Shufeng Jiedu Capsules alone or in combination with conventional western medicine for treating influenza were retrieved from PubMed, EMbase, Cochrane Library, Web of Science, SinoMed, CNKI, VIP, Wanfang, and ClinicalTrails.gov. The data analysis was performed in RevMan 5.4.1. The Cochrane risk of bias assessment tool was used to evaluate the quality of the involved RCT, and GRADEpro GDT to assess the quality of the evidence. A total of 11 RCTs involving 1 836 patients were included in this study. Compared with conventional western medicine, Shufeng Jiedu Capsules/Shufeng Jiedu Capsules + conventional western medicine improved the response rate(RR=1.09, 95%CI[1.03, 1.15], P=0.002), shortened the time to relief of cough, and increased the 3-day sore throat relief rate, whereas there was no significant difference in the time to fever abatement, the time to relief of sore throat, 3-day cough relief rate, or 3-day runny nose relief rate. Subgroup-analysis showed that Shufeng Jiedu Capsules + conventional western medicine improved the response rate(RR=1.11, 95%CI[1.08, 1.15], P<0.000 01), shortened the time to relief of cough, and increased the 3-day relief rate of symptoms(cough, sore throat, and runny nose) compared with conventional western medicine alone, while there was no significant difference in the time to fever abatement or the time to relief of sore throat. Shufeng Jiedu Capsules alone could not improve the response rate(RR=0.97, 95%CI[0.93, 1.02], P=0.19). In addition, Shufeng Jiedu Capsules/Shufeng Jiedu Capsules + conventional western medicine vs conventional western medicine were no significant difference in adverse reactions(RR=0.98, 95%CI[0.57, 1.69], P=0.95). The available evidence suggests that Shufeng Jiedu Capsules is effective and safe in the treatment of influenza, and the combination of Shufeng Jiedu Capsules with conventional western medicine can accelerate the relief of symptoms. However, since the number and quality of the included studies were low, the above findings remained to be further verified by multicenter RCT with large sample sizes.

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.

Experimental Study on the Mechanism of Mangiferin Inhibiting Malignant Biological Characteristics of Multiple Myeloma and Exerting Anticancer Effect / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of pure Chinese herbal extract Mangiferin on the malignant biological behaviors of multiple myeloma (MM) cells, and to analyze the molecular mechanism of the anti-myeloma effect of Mangiferin, so as to provide experimental basis for MM replacement therapy.@*METHODS@#U266 and RPMI8226 of human MM cell lines were intervened with different concentrations of Mangiferin. Cell proliferation was detected by CCK-8 method. Annexin V/PI double staining flow cytometry was used to detect cell apoptosis. Western blot was used to detect the expression of apoptosis and related signaling pathway proteins, and real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of matrix metalloproteinase (MMP) and CXC chemokine receptor (CXCR) family.@*RESULTS@#Mangiferin could inhibit the proliferation activity of U266 and RPMI8226 cells and induce cells apoptosis. After Mangiferin intervened in U266, RPMI8226 cells for 48 h, the expression of Bcl-2 family pro-apoptotic protein Bax was up-regulated, while the expression of survivin and Bcl-xL proteins was down-regulated and caspase-3 was hydrolyzed and activated to promote cell apoptosis, besides, the expression of Bcl-2 protein in U266 cells was also significantly down-regulated to induce apoptosis (P<0.05). After Mangiferin intervenes in MM cells, it can not only increase the expression level of tumor suppressor p53, but also induce programmed cell death of MM cells by inhibiting the expression of anti-apoptotic molecules and down-regulating the phosphorylation levels of AKT and NF-κB. In addition, after the intervention of Mangiferin, the expressions of CXCR4, MMP2 and MMP9 in U266 cells were down-regulated (P<0.05), while there is no effect on the expressions of CXCR2, CXCR7 and MMP13 (P>0.05). However, the expressions of CXCR4, MMP9, and MMP13 in RPMI8226 cells were down-regulated (P<0.01), the expression of MMP2 was weakly affected, and the expression of CXCR2 and CXCR7 was basically not affected (P>0.05).@*CONCLUSION@#Mangiferin can inhibit the proliferation and induce apoptosis of MM cells, and its mechanism may be related to inhibiting the activation of NF-κB signaling pathway, affecting the expression of Bcl-2 family proteins, and inhibiting the expression of core members of MMP and CXCR family.

The Effects and Regulatory Mechanism of Targeting CXC Chemokine Receptor 1/2 Combined with Ara-C on the Malignant Biological Behaviors of U937 Cells of Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate and analyze the effect of CXC chemokine receptor 1/2 (CXCR1/2) targeting inhibitor Reparixin combined with cytarabine (Ara-C) on the malignant biological behaviors of acute myeloid leukemia cells and its effect on the expression of the CXCR family, while exploring the accompanying molecular mechanism, providing scientific basis and reference for new molecular markers and targeted therapy for AML.@*METHODS@#Acute myeloid leukemia U937 cells were treated with different concentrations of Reparixin, Ara-C alone or in combination, and the cell morphology was observed under an inverted microscope; Wright-Giemsa staining was used to detect cell morphological changes; CCK-8 method was used to detect cell proliferation; the ability of cell invasion was detected by Transwell chamber method; the ability of colony formation was detected by colony formation assay; cell apoptosis was detected by Hoechst 33258 fluorescent staining and Annexin V/PI double-staining flow cytometry; monodansylcadaverine(MDC) staining was used to detect cell autophagy; the expression of apoptosis, autophagy and related signaling pathway proteins was detected by Western blot and the expression changes of CXCR family were detected by real-time quantitative polymerase chain reaction (qRT-PCR).@*RESULTS@#Reparixin could inhibit the proliferation, invasion, migration and clone formation ability of U937 cells. Compared with the single drug group, when U937 cells were intervened by Reparixin combined with Ara-C, the malignant biological behaviors such as proliferation, invasion and colony formation were significantly decreased, and the levels of apoptosis and autophagy were significantly increased (P<0.01). After Reparixin combined with Ara-C intervenes in U937 cells, it can up-regulate the expression of the pro-apoptotic protein Bax and significantly down-regulate the expression of the anti-apoptotic protein Bcl-2, and also hydrolyze and activate Caspase-3, thereby inducing cell apoptosis. Reparixin combined with Ara-C could up-regulate the expressions of LC3Ⅱ and Beclin-1 proteins in U937 cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P<0.01). MDC result showed that the green granules of vesicles increased significantly, and a large number of broken cells were seen (P<0.01). Reparixin combined with Ara-C can significantly inhibit the phosphorylation level of PI3K, AKT and NF-κB signaling molecule, inhibit the malignant biological behavior of cells by inhibiting the activation of PI3K/AKT/NF-κB pathway, and induce programmed cell death. Ara-C intervention in U937 cells had no effect on the expression of CXCR family (P>0.05). The expression of CXCR1, CXCR2, and CXCR4 mRNA could be down-regulated by Reparixin single-agent intervention in U937 cells (P<0.05), and the expression of CXCR2 was more significantly down-regulated than the control group and other CXCRs (P<0.01). When Reparixin and Ara-C intervened in combination, the down-regulated levels of CXCR1 and CXCR2 were more significant than those in the single-drug group (P<0.01), while the relative expressions of CXCR4 and CXCR7 mRNA had no significant difference compared with the single-drug group (P>0.05).@*CONCLUSION@#Reparixin combined with Ara-C can synergistically inhibit the malignant biological behaviors of U937 cells such as proliferation, invasion, migration and clone formation, and induce autophagy and apoptosis. The mechanism may be related to affecting the proteins expression of Bcl-2 family and down-regulating the proteins expression of CXCR family, while inhibiting the PI3K/AKT/NF-κB signaling pathway.

Efficacy and safety of Regan Syrup in treatment of common cold (wind-heat syndrome):a multicenter, randomized, double-blind, double-dummy, placebo and positive drug-controlled, parallel, phase Ⅱb clinical trial / 中国中药杂志

Regan Syrup has the effect of clearing heat, releasing exterior, benefiting pharynx and relieving cough, and previous phase Ⅱ clinical trial showed that the efficacy of Regan Syrup high-dose and low-dose groups was better than that of the placebo group, and there was no statistically significant difference in the safety between the three groups. The present study was conducted to further investigate the efficacy and safety of the recommended dose(20 mL) of Regan Syrup in the treatment of common cold(wind-heat syndrome). Patients who met the inclusion and exclusion criteria were selected and divided into the test group(Regan Syrup+Shufeng Jiedu Capsules placebo), positive drug group(Regan Syrup placebo+Shufeng Jiedu Capsules) and placebo group(Regan Syrup placebo+Shufeng Jiedu Capsules placebo) at a 1∶1∶1 using a block randomization method. The course of treatment was 3 days. A total of 119 subjects were included from six study centers, 39 in the test group, 40 in the positive drug group and 40 in the placebo group. The onset time of antipyretic effect was shorter in the test group than in the placebo group(P≤0.01) and the positive drug group, but the difference between the test group and the positive drug group was not significant. The test group was superior to the positive drug group in terms of fever resolution(P<0.05), and had a shorter onset time of fever resolution than the placebo group, but without obvious difference between the two groups. Compared to the positive drug group, the test group had shortened disappearance time of all symptoms(P≤0.000 1). In addition, the test group was better than the positive drug group and the placebo group in relieving symptoms of sore throat and fever(P<0.05), and in terms of clinical efficacy, the recovery rate of common cold(wind-heat syndrome) was improved in the test group compared to that in the placebo group(P<0.05). On the fourth day after treatment, the total TCM syndrome score in both test group and positive drug group was lower than that in the placebo group(P<0.05). There was no significant difference in the incidence of adverse events between three groups and none of them experienced any serious adverse events related to the study drug. The results indicated that Regan Syrup could shorten the onset time of antipyretic effect, reduce the time of fever resolution, alleviate the symptoms such as sore throat and fever caused by wind-heat cold, reduce the total score of Chinese medicine symptoms, and improve the clinical recovery rate with good safety.

The outcome of transnasal endoscopic total maxillectomy in the treatment of sinonasal adenoid cystic carcinoma / 临床耳鼻咽喉头颈外科杂志

Objective:To assess the prognosis of sinonasal adenoid cystic carcinoma with hard palatine invasion treated by transnasal endoscopic total maxillectomy. Methods:Clinical data of twenty-six patients with sinonasal adenoid cystic carcinoma invading hard palatine treated by transnasal endoscopic total maxillectomy between May 2014 and December 2020 was analyzed retrospectively. Survival rate, local recurrence and distant metastasis were analyzed using Kaplan-Meier method. Cox regression was used to investigate the prognosis factors. Masticatory function after maxillectomy has also been assessed using the questionnaire of patients' satisfaction about masticatory function. Results:Margins in 8 patients（30%） were positive. The median time of follow-up was 38 months（6 to 85 months）. Twenty-five patients recurred. Four patients died of distant metastasis. The 5-year overall survival rate and relapse-free survival rate was 79.5% and 89.1%, respectively. Independent predictors of outcome on multivariate analysis were positive margin（P=0.018）, recurrence（P=0.006） and distant metastasis（P=0.04）. Conclusion:Transnasal endoscopic total maxillectomy could be performed for the treatment of the sinonasal adenoid cystic carcinoma with hard palatine invasion. Positive margin, local recurrence and distant metastasis were important predictors for patients' prognosis.

Endoscopic transoral approach nasopharyngectomy for petroclival and jugular foramen nasopharyngeal carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To describe a technique of endoscopic transoral approach nasopharyngectomy for petroclival and jugular foramen nasopharyngeal carcinoma, based on anatomic studies and surgeries. Methods: Three dry human skulls and five fresh human cadaver heads were used for anatomic study of a endoscopic transoral approach to expose petroclival and jugular foramen. The anatomical landmarks and the extent of exposure were recorded. Six clinical cases who were treated in Eye & ENT Hospital, Fudan University from June 2020 to April 2022 were used to illustrate the technique and feasibility of this approach and to assess its indications and advantages, including 3 males and 3 females, aged 42 to 69 years old. Descriptive analysis was used in this research. Results: On the basis of the preservation of the internal pterygoid muscle and the external pterygoid muscle, this approach could fully expose the parapharyngeal, petrosal and paraclival segment internal carotid arteries, and safely deal with the lesions of jugular foramen and petroclival region. The 6 patients in our study tolerated the procedure well. Postoperative enhanced MRI showed complete resection of the tumor and no postoperative masticatory dysfunction. Conclusion: Endoscopic transoral approach is a safe, minimally invasive and effective surgical treatment for petroclival and jugular foramen recurrent nasopharyngeal carcinoma.

Effects and mechanism of Morus alba L. (Sangzhi) alkaloids combined with metformin on glucose metabolism in diabetic KKAy mice / 药学学报

To investigate the effects and mechanism of the combination of Morus alba L. (Sangzhi) alkaloids(SZ-A) and metformin (Met) on glucose metabolism in type 2 diabetic mice, KKAy mice were divided into four groups according to the glucose and lipid indexes: control group (control), Morus alba L. (Sangzhi) alkaloids group (SZ-A, 100 mg·kg-1), metformin group (Met, 100 mg·kg-1) and combined administration group (combination, Comb, 100 mg·kg-1 SZ-A + 100 mg·kg-1 Met). All groups were administered by gavage once daily for 7 weeks accompanied with monitoring food intake, water intake, body weight as well as glycemia. Additionally, oral glucose tolerance test (OGTT), insulin tolerance test (ITT) and oral sodium pyruvate tolerance test (OPTT) were performed at week 2, week 5, week 6, respectively. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (00004332). We determined the weight and lipid content of liver, and then performed the histopathological analysis after sacrificed. Furthermore, Western blot assay was used to detect the protein levels of key molecules of PI3K/PDK1/Akt/GLUT signaling pathway in liver, muscle and adipose tissue. Compared to the SZ-A or Met monotherapy group, SZ-A + Met significantly improved the glucose metabolism disorder, which was showed in reduced food intake, water intake, the level of fasting blood glucose, postprandial blood glucose and glycosylated hemoglobin A1c (HbA1c) of KKAy mice, as well as improved glucose tolerance, enhanced insulin sensitivity and inhibited gluconeogenesis. In addition, SZ-A + Met obviously up-regulated the protein expression levels in PI3K/PDK1/Akt/GLUT signaling pathway in liver, muscle and adipose tissue of KKAy mice. Moreover, the liver lipid accumulation and blood aminotransferase level of KKAy mice in the combined administration group were significantly reduced. Therefore, we concluded that the combination of SZ-A and Met improved glucose metabolism and inhibited the occurrence and development of T2DM via promoting glucose uptake and utilization, suggesting that the combination of SZ-A and Met is a more useful treatment for T2DM.

Advances in histone epigenetic enzyme inhibitors based on proteomics / 药学学报

As an important component of nucleosomes on the chromatin of eukaryotic cells, histones play an important role in the development and progression of tumour diseases by regulating epigenetic post-translational modifications such as acetylation and methylation. In addition, development of inhibitors targeting methyltransferase and deacetylase provides novel therapeutic strategies for cancer treatment. Mass spectrometry-based proteomics can reveal the global changes of histone modifications under the action of drugs during disease progression, which in turn provides important support for revealing drug action mechanism, drug resistance mechanism, and investigating novel drug combination strategies. This article focuses on the progress and status of proteomic research on a variety of histone modifying enzyme inhibitors, including methyltransferase inhibitors and histone deacetylase inhibitors, which will help to understand the current and further utilization of proteomics in studying histone modifications.

Epidemiology of pathogenic tick-borne viruses in China: a review / 中国血吸虫病防治杂志

Ticks are obligate, haematophagous arthropods that are distributed across the world, which may transmit more than 200 pathogens, including viruses, bacteria and parasites. A large number of tick species are widespread in China, and their transmitting tick-borne viral diseases pose a great threat to human health in endemic foci. This review describes the epidemiology of common, emerging and potentially pathogenic tick-borne viruses in China, and recommends the assessment of public health significance and pathogenicity of emerging tick-borne viruses using reverse microbial etiology, so as to provide insights into the management of emerging tick-borne diseases in China.

Analysis of Tumor Immune Microenvironment Based on Bulk RNA-sequencing Data and Its Application / 肿瘤防治研究

Cancer immunotherapy is one of the most promising biological therapies. The dynamic changes of the immune microenvironment of heterogeneous tumors are critical factors in determining the interaction and therapeutic efficacy between tumor and immune microenvironment. Therefore, quantitative analysis of its constituent cells, related genes, and phenotypes in real time is of great importance. The methods used to analyze tumor immune microenvironment include immunohistochemistry, flow cytometry and so on. With the development of next-generation sequencing technology, transcriptome RNA sequencing data analysis has become one of the important methods to determine the composition of tumor immune microenvironment. This article focuses on the common methods of bulk RNA sequencing data analysis and related research progress.

In vitro bacteriostatic and serum pharmacological tests of Qiguiyin decoction combined with levofloxacin against pseudomonas aeruginosa / 中国药理学通报

Aim To investigate the antibacterial activity and anti-resistant mutation ability of Qiguiyin decoction (a traditional Chinese herbal formula) combined with levofloxacin against pseudomonas aeruginosa byantibacterial experiment in vitro and serum pharmacology. Methods The minimal inhibitory concentrations (MICs) of levofloxacin and Qiguiyin decoction were detected respectively by the broth dilution technique.The MIC of the combination of two drugs was determined by the micro chessboard dilution method. The effects of combined drugs on enhancing the antibacterial activity of different strains were evaluated respectively by calculating the fractional inhibitory concentration index (FICI). The drug-containing serum of levofloxa-cin group, Qiguiyin decoction group, Qiguiyin decoction combined with levofloxacin group and control group was prepared. The antibacterial rate, MIC and MBC of 10% ~ 90% serum against the two strains were determined. Results Combined with Qiguiyin decoction, MIC of levofloxacin against pseudomonas aeruginosa (standard/resistant) decreased significantly, 0. 5 < FICI

The effect and mechanism of metformin on peripheral neuropathy in type 1 diabetic rats / 药学学报

Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications occurring in both type 1 and type 2 diabetes mellitus patients, which often results in patients suffering from severe hyperalgesia and allodynia. Up to now, the clinical therapeutic effect of DPN is still unsatisfactory. Metformin is an anti-diabetic drug that has been safely and widely used for the treatment of type 2 diabetes for decades. Studies have shown that metformin can improve pain caused by DPN, but its effects on the nerve conduction velocity and morphology of the sciatic nerve of DPN, and the mechanism for improving DPN are not clear. Therefore, the STZ-induced model of type 1 DPN in SD rats was used to study the effects of metformin on DPN, and to preliminarily explore its mechanism in this study. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). After the model was established successfully, STZ diabetic rats were randomly divided into a model group and a metformin treatment group, and 10 normal SD rats were selected as the normal control group, and the rats were intragastrically administered for 12 weeks. The results showed that metformin significantly reduced blood glucose, glycosylated hemoglobin, food consumption and water consumption in STZ rats. Metformin markedly increased the motor nerve conduction velocity and mechanical stabbing pain threshold, prolonged the hot plate latency threshold, and improved the pathological morphological abnormalities of the sciatic nerve in STZ rats. In addition, metformin increased the content of glutathione (GSH), enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and reduced the content of malondialdehyde (MDA) in serum and sciatic nerve of STZ diabetic rats, as well as regulating the expression of genes related to oxidative stress in the sciatic nerve. Metformin obviously reduced the levels of pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in the serum in STZ rats, and inhibited the gene expression of these inflammatory factors in the sciatic nerve. In summary, metformin significantly increased nerve conduction velocity, improved sciatic nerve morphological abnormalities and pain in DPN rats, which may be related to its effect in improving oxidative stress and reducing inflammation.