Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics / 药学学报

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Xixin Decoction improves learning and memory ability of SAMP8 by enhancing neuroprotective effect and inhibiting neuroinflammation / 中国中药杂志

This study aimed to explore the possible effect of Xixin Decoction(XXD) on the learning and memory ability of Alzheimer's disease(AD) model senescence-accelerated mouse-prone 8(SAMP8) and the related mechanism in enhancing neuroprotective effect and reducing neuroinflammation. Forty SAMP8 were randomly divided into a model group(10 mL·kg~(-1)·d~(-1)), a probiotics group(0.39 g·kg~(-1)·d~(-1)), a high-dose group of XXD granules(H-XXD, 5.07 g·kg~(-1)·d~(-1)), a medium-dose group of XXD granules(M-XXD, 2.535 g·kg~(-1)·d~(-1)), and a low-dose group of XXD granules(L-XXD, 1.267 5 g·kg~(-1)·d~(-1)). Eight senescence-accelerated mouse-resistant 1(SAMR1) of the same age and strain were assigned to the control group(10 mL·kg~(-1)·d~(-1)). After ten weeks of intragastric administration, the Morris water maze was used to test the changes in spatial learning and memory ability of mice after treatment. Meanwhile, immunofluorescence staining was used to detect the positive expression of receptor for advanced glycation end products(AGER), Toll-like receptor 1(TLR1), and Toll-like receptor 2(TLR2) in the hippocampal CA1 region of mice. Western blot was employed to test the protein expression levels of silencing information regulator 2 related enzyme 1(SIRT1), AGER, TLR1, and TLR2 in the hippocampus of mice. Enzyme linked immunosorbent assay(ELISA) was applied to assess the levels of Aβ_(1-42) in the hippocampus of mice and the levels of nuclear factor κB p65(NF-κB p65), NOD-like receptor protein 3(NLRP3), tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) in the serum and hippocampus of mice. Compared with the model group, XXD significantly improved the spatial learning and memory ability of SAMP8, increased the expression of neuroprotective factors in the hippocampus, decreased the levels of neuroinflammatory factors, and inhibited the expression of Aβ_(1-42). In particular, H-XXD significantly increased the expression of SIRT1 in the hippocampus of mice, reduced the expression levels of NF-κB p65, NLRP3, TNF-α, and IL-1β in the serum and hippocampus of mice, and decreased the expression of AGER, TLR1, and TLR2 in the hippocampus of mice(P<0.05 or P<0.01). XXD may improve the spatial learning and memory ability of AD model SAMP8 by enhancing the neuroprotective effect and inhibiting neuroinflammation.

Picomolar inhibitor of reverse transcriptase featuring significantly improved metabolic stability

Considering the undesirable metabolic stability of our recently identified NNRTI 5 (t1/2 = 96 min) in human liver microsomes, we directed our efforts to improve its metabolic stability by introducing a new favorable hydroxymethyl side chain to the C-5 position of pyrimidine. This strategy provided a series of novel methylol-biphenyl-diarylpyrimidines with excellent anti-HIV-1 activity. The best compound 9g was endowed with remarkably improved metabolic stability in human liver microsomes (t1/2 = 2754 min), which was about 29-fold longer than that of 5 (t1/2 = 96 min). This compound conferred picomolar inhibition of WT HIV-1 (EC50 = 0.9 nmol/L) and low nanomolar activity against five clinically drug-resistant mutant strains. It maintained particularly low cytotoxicity (CC50 = 264 μmol/L) and good selectivity (SI = 256,438). Molecular docking studies revealed that compound 9g exhibited a more stable conformation than 5 due to the newly constructed hydrogen bond of the hydroxymethyl group with E138. Also, compound 9g was characterized by good safety profiles. It displayed no apparent inhibition of CYP enzymes and hERG. The acute toxicity assay did not cause death and pathological damage in mice at a single dose of 2 g/kg. These findings paved the way for the discovery and development of new-generation anti-HIV-1 drugs.

Research on Mechanisms of Chinese Medicines in Prevention and Treatment of Postoperative Adhesion / 中国结合医学杂志

Postoperative adhesion (PA) is currently one of the most unpleasant complications following surgical procedures. Researchers have developed several new strategies to alleviate the formation of PA to a great extent, but so far, no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention. Chinese medicine (CM) has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine. Therefore, this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments, including their pharmacological effects, therapeutic mechanisms and advantages in PA prevention. We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.

Correlation analysis of asthma and prognosis in 148 children with low immune function / 公共卫生与预防医学

Objective To analyze the effect of immune function on the condition and prognosis of asthma in children with asthma. Methods A total of 148 children with asthma diagnosed in Qinghai women and children's Hospital from January 2018 to January 2021 were included in the analysis, the immune function of the children was determined, and the information of all children was followed up for 6 months after treatment; compared The condition and follow-up prognosis of children with immunocompromised and normal immune function were analyzed and discussed, and the correlation between the expression levels of immunoglobulins (IgG, IgA, IgM) and the condition and short-term recurrence prognosis (6 months) of children was analyzed and discussed, so as to guide Prevention and clinical work. Statistical analysis was done using SPSS19.0. Results The average age of 148 children with recurrent respiratory tract infection in the study was (8.94±3.65) years old, including 70 male children. The condition of the children was evaluated and classified into mild/severe cases: 148 children in this study included mild cases. There were 98 cases and 50 severe cases. There were more males and lower BMI levels in severe children (P<0.05) . The levels of IgG, IgA and IgM in children were all lower in severe children (P<0.05) . The follow-up found that the proportion of relapses in critically ill children was higher (P<0.05). Comparing the levels of IgG, IgA, and IgM in mild and severe children, the average levels of IgG, IgA, and IgM in severe children were lower than those in the mild group, and the difference was statistically significant (P<0.05); recurrence within 6 months of follow-up Prognostic evaluation showed that 19 of the 148 children had relapse, and the levels of IgG, IgA, and IgM in severe relapsed children were significantly lower than those without relapse (P<0.05). Analysis of the relevant factors potentially affecting the prognosis of recurrence showed that gender (female) (OR=1.726) , BMI level (weight loss) (OR=1.613) , IgG expression level factor (low expression) (OR=1.898) , IgA expression Level factor (low expression) (OR=3.509) , IgM expression level factor (low expression) (OR=3.217) and disease factor (severe) (OR=3.619) were potential risk factors, which would increase the risk of poor prognosis. Conclusion The asthma attack in children with immunocompromised immune function is relatively severe, and the short-term recurrence probability is higher, which deserves clinical attention and preventive intervention.

Changes in serum levels of Hcy and MMP-9 and risk factor analysis in patients with coronary heart disease complicating Helicobacter pylori infection in Chengdu area / 公共卫生与预防医学

Objective To study the changes in serum homocysteine (Hcy) and matrix metalloproteinase-9 (MMP-9) levels and risk factors in patients with coronary heart disease (CHD) complicated with Helicobacter pylori (HP) infection in Chengdu area, and to provide a theoretical basis for the prevention of HP infection in patients with coronary heart disease. Methods A total of 348 CHD patients admitted to our hospital in Chengdu from 2019 to 2021 were selected. Hp infection status was detected by C14 urea breath test. Patients were classified into control group (n=197) and HP infection group (n=151) according to the detection results. Data including gender, age, body mass index and peptic ulcer history were collected, and univariate analysis and logistic regression were used to screen the risk factors affecting the occurrence of HP infection in patients with CHD. Results The prevalence rate of HP infection was 43.39% (151/348) among the selected CHD patients. Serum levels of Hcy and MMP-9 were notably elevated in HP infection group compared with control group (P<0.05). The proportion of patients with age ≥60 years old, hyperlipidemia, proton pump inhibitor use history, and frequent consumption of out-of-home food and spicy food in HP infection group was obviously larger than that in control group (P<0.05). Hyperlipidemia (OR=3.719), history of proton pump inhibitor use (OR=3.254) and frequent consumption of out-of-home food (OR=2.721) were independent risk factors for HP infection in CHD patients (P<0.05). Conclusion CHD patients in Chengdu suffer a prevalence rate of HP infection, and have elevated levels of serum Hcy and MMP-9. Furthermore, the intervention measures for patients with hyperlipidemia, proton pump inhibitor drug use history and frequent consumption of out-of-home food are of vital importance for decreasing the risk of HP infection.

Screening novel inhibitors of squalene epoxidase and their effects on hepatocellular carcinoma / 药学学报

Squalene epoxidase (SQLE) is a potential target for the treatment of liver cancer. Bioinformatics analysis indicated that the high expression of SQLE was closely related to the clinical stage and poor prognosis of patients with liver cancer. However, the existing inhibitors against SQLE 195 tyrosine residue (Y195) cannot be used clinically due to severe side effects. In this study, 35 small-molecule compounds targeting SQLE 335 tyrosine residue (Y335) were selected by computer virtual screening. Combined with MTT assay, 3 candidate compounds (19#, 31# and 35#) with significant inhibitory effects on the proliferation of Huh7 cell line were obtained. Further studies showed that these 3 compounds could inhibit the migration of Huh7 cells, reduce the contents of total and free cholesterol, up-regulate the expression of tumor suppressor gene PTEN, and down-regulate the expression of PI3K and AKT proteins. The results showed that the novel inhibitors 19#, 31# and 35# targeting SQLE Y335 could reduce cholesterol content, inhibit the proliferation and migration of Huh7, thus playing an anti-liver cancer role.

Ginsenoside Rg1 injection combined with inosine tablets and vitamin B1 for the treatment of primary retinitis pigmentosa / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effects of ginsenoside Rg1 injection combined with inosine tablets and vitamin B1 on serum brain-derived neurotrophic factor(BDNF), pituitary adenylate cyclase activating polypeptide(PACAP)and clinical efficacy in primary retinitis pigmentosa.METHODS: A total of 50 patients(100 eyes)with primary retinitis pigmentosa who admitted to the Department of Ophthalmology, the Second Affiliated Hospital of Hebei North University from August 2019 to March 2022 were selected as the research object. They were divided into the study group and the control group according to random number table, with 50 eyes in each group. Patients in the control group were treated with inosine tablets and vitamin B1, while patients in the study group were treated with ginsenoside Rg1 injection on the basis of the control group. The expression of BDNF and PACAP in serum, electroretinogram and spectral-domain optical coherence tomography(SD-OCT)were compared before and after treatment, and the retinal thickness(RT), mean deviation(MD), clinical efficacy and safety indexes were compared between the two groups.RESULTS: There were no differences in the MD of the two groups before treatment(t=1.670, P=0.098), while the MD of the study group was significantly lower than that of the control group after treatment(t=3.628, P&#x003C;0.01). Before treatment, RT with a diameter of 1mm at the circle of macular fovea was compared between the two groups(t=0.108, P=0.914), it was significantly higher than that in the control group after treatment(t=6.125, P&#x003C;0.01). Before treatment, there was no significant difference in the results of dark adaptation of electroretinogram between the two groups(all P&#x003E;0.05). After treatment, the results of dark adaptation in the study group were significantly better than those in the control group(all P&#x003C;0.01). Before treatment, there was no significant difference in the results of electroretinogram adaptation between the two groups(all P&#x003E;0.05). After treatment, the results of electroretinogram adaptation in the study group were significantly better than those in the control group(all P&#x003C;0.01). There was no significant difference in BDNF and PACAP between the two groups before treatment(all P&#x003E;0.05). BDNF and PACAP in the study group were higher than those of the control group after treatment(all P&#x003C;0.01). After treatment, no adverse reactions were observed in both groups.CONCLUSION: The treatment of patients with primary retinitis pigmentosa with ginsenoside will improve the retinal function and promote the prognosis of the disease by regulating the expression of BDNF and PACAP, and it is highly safe.

Differences in Contents and Formation Methods of Clinical Questions in Chinese and Korean Clinical Practice Guidelines of Acupuncture-Moxibustion: Scoping Review / 中国结合医学杂志

OBJECTIVE@#To analyze the differences in the needs of users and the value orientation of clinical practice guidelines (CPGs) by comparing the contents and formation methods of clinical questions in Chinese and Korean CPGs of acupuncture-moxibustion (Acup-Mox).@*METHODS@#The full text of CPGs was systematically searched from the official websites of Chinese and Korean traditional medicine societies and Acup-Mox associations, with the topic "Acup-Mox for treating diseases" and the retrieval time up to September 28, 2022. Two researchers screened the CPGs independently, and extracted the guidelines' topics, content, quantity and formation methods of clinical questions. The quantitative data were collected by counting the frequency, and the qualitative data were classified and described by thematic analysis.@*RESULTS@#A total of 29 guidelines were included in this study, including 20 Chinese guidelines (305 questions) and 9 Korean guidelines (223 questions). The differences lie in the aspects of content and diversity, and formation method. As for content and diversity, Chinese guidelines focused mainly on the questions related to treatment such as the operation of specific intervention (86, 28.2%), efficacy of intervention (78, 25.6%), and also involving questions in diagnosis, prevention, and prognosis. While the clinical questions in Korean guidelines were concentrated to efficacy of intervention (218, 97.8%). As for formation method, in Chinese guidelines, questions were usually collected directly from clinicians, and then determined and optimized by experts. In Korean guidelines, frequently used clinical Acup-Mox interventions would be screened first. Then the expert group would set up corresponding intervention control measures so as to form clinical questions related to treatment efficacy.@*CONCLUSIONS@#The differences reflect the different needs of clinical practitioners, and the different aims or concepts in developing Acup-Mox guidelines between China and South Korea. Chinese guidelines emphasized promoting operation protocols and techniques of Acup-Mox for practical use, while Korean guidelines emphasized promoting the frequently used clinical intervention therapies. It is speculated that the guidelines from these two countries would play different roles in guiding clinical operation and supporting medical decision. In terms of formation methods of clinical questions, it is suggested to attach importance to optimizing process in formatting clinical questions to improve the clinical applicability of CPGs of Acup-Mox.

Research progress on structure, function and disease correlation of solute carrier family 4 / 生理学报

The solute carrier family 4 (SLC4) includes 10 members (SLC4A1-5, SLC4A7-11), which are expressed in multiple tissues in the human body. The SLC4 family members differ in their substrate dependence, charge transport stoichiometry and tissue expression. Their common function is responsible for the transmembrane exchange of multiple ions, which is involved in many important physiological processes, such as erythrocyte CO2 transport and the regulation of cell volume and intracellular pH. In recent years, many studies have focused on the role of SLC4 family members in the occurrence of human diseases. When SLC4 family members have gene mutations, a series of functional disorders will occur in the body, leading to the occurrence of some diseases. This review summarizes the recent progress about the structures, functions and disease correlation of SLC4 members, in order to provide clues for the prevention and treatment of related human diseases.

Effect of transcutaneous acupoint electrical stimulation at Neiguan (PC 6) on general anesthesia under preserving spontaneous breathing in thoracoscopic lobectomy / 中国针灸

OBJECTIVE@#To evaluate the effect of transcutaneous acupoint electrical stimulation (TEAS) at Neiguan (PC 6) on general anesthesia under preserving spontaneous breathing in thoracoscopic lobectomy.@*METHODS@#A total of 66 patients of primary lung cancer undergoing thoracoscopic lobectomy were divided to an observation group (33 cases, 1 case discontinued) and a control group (33 cases). In the observation group, TEAS at Neiguan (PC 6) was used 30 min before anesthesia induction till the end of surgery. The surgery time, maximum value of partial pressure of end-tidal carbon dioxide (PETCO2) and minimum value of oxygen saturation (SpO2) of the two groups were recorded. The dosage of propofol, sufentanil, remifentanil and dexmedetomidine were analyzed. Separately, before induction (T0), at the start of surgery (T1), thoracic exploration (T2) and lobectomy (T3), as well as 30 min (T4) and 60 min (T5) after lobectomy, the mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), serum cortisol (Cor) and norepinephrine (NE) were measured. The time of post anesthesia care unit (PACU) stay, ambulation, flatus, chest drainage and the incidence of nausea and vomiting were compared between the two groups.@*RESULTS@#The maximum value of PETCO2, the dosage of propofol and remifentanil in the observation group were lower than those in the control group (P < 0.05, P < 0.01), the minimum value of SpO2 in the observation group was higher than that of the control group (P < 0.01). At T1-T5, the MAP, HR, serum Cor and NE levels in the observation group were all lower than those in the control group (P < 0.05). The ambulation time, the time for the flatus, chest drainage time, and the incidence of nausea and vomiting in the observation group were all lower than those in the control group (P<0.001, P < 0.01).@*CONCLUSION@#For the general anesthesia under preserving spontaneous breathing in thoracoscopic surgery, TEAS at Neiguan (PC 6) relieves stress response, reduces opioids dosage and promotes postoperative recovery.

Overview on the modern development of fire needling device: from tradition to innovation / 中国针灸

The appropriate needle device is crucial for obtaining the curative effect of fire needling therapy. The article introduces the material specification, clinical operation, indications, characteristics and advantages of the contemporary traditional fire needling devices (e.g. He's fire needle and Shi 's fire needle) and the contemporary new-type ones (e.g. fire needling with filiform needle and micro-needle); and determines the innovations of modern fire needling. It is anticipated that the needle specifications, production process and operation standard of fire needling devices should be further unified so as to provide the references for the selection of fire needling devices in treatment based on clinical syndrome differentiation and expand the clinical application of fire needling therapy.

Study on the relationship between the age at natural menopause and postmenopausal metabolic syndrome / 中华预防医学杂志

To explore the relationship between the early or delayed age at natural menopause and metabolic syndrome (MS) in women. A total of 4 734 natural menopausal women who completed the baseline survey from November 2017 to January 2020 in the Guangzhou Middle-aged and Elderly Chronic Disease Prospective Cohort Study were selected in this cross-sectional study. Data on general demographic characteristics, disease history and female physiological health indicators were collected. Logistic regression model and restricted cubic spline curve were used to analyze the relationship between the age at natural menopause and MS. The results showed that the mean age of the subjects was (60±6) years old. The median (Q1,Q3) age at natural menopause was 50 (49, 52) years old, and the prevalence of MS was 14.8%(699/4 734). After adjusting for confounders, the age at natural menopause was closely related to MS in an approximate"U"shape. Compared with the group of normal age at natural menopause, the early age at menopause (OR=1.52, 95%CI: 1.12-2.06) and delayed age at menopause (OR=1.77, 95%CI: 1.36-2.30) had a higher risk of MS. In the group with time since menopause ≤6 years and 7-9 years, the risk of MS in the group with delayed age at menopause was 2.40 times (95%CI: 1.54-3.75) and 2.19 times (95%CI: 1.11-4.31) higher than that in the group with normal menopausal age, respectively. In conclusion, the early and delayed age at natural menopause increased the risk of MS. The increased risk of MS in delayed age at natural menopause mainly occurred within 10 years since menopause.

Research progress on drug resistance of anti-varicella-zoster virus drugs / 中华预防医学杂志

Varicella-zoster virus (VZV) causes chickenpox when it first infects humans, and the virus may reactivate in adulthood and cause herpes zoster (HZ). Broad-spectrum antiviral drugs are one of the treatments for varicella and herpes zoster, but the emergence of drug resistance poses many challenges to this treatment and increases the burden of disease on patients. This paper discusses the resistance mechanisms, resistance sites and resistance detection methods of anti-VZV drugs in order to help further research on new anti-VZV targets, new drugs and monitoring of resistance to existing drugs.

Effects of paclitaxel on Müller cells in retina / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effects of antitumor drug paclitaxel(PTX)on the proliferation, apoptosis, cell cycle, cell morphology, and related protein expression of Müller cells, and to evaluate its potential toxicity to the retina.METHODS:Müller cells were cultured in vitro and divided into two groups: control group(normal medium)and PTX group. Retinal Müller cells were treated with different concentrations of PTX(0.005, 0.05, 0.5 and 5mg/L)for varying durations(12, 24, 36, 48 and 72h). The CCK8 method was used to assess the effects of different concentrations of PTX and treatment duration on the proliferation Müller cells. Flow cytometry was employed to investigate the impact of different concentrations of PTX on Müller cells apoptosis and cell cycle arrest. Immunofluorescence was used to observe morphological changes in Müller cells. The effects of PTX on the expression of apoptosis-related proteins and aquaporins were analyzed by Western blot and qRT-PCR.RESULTS: PTX exhibits the ability to inhibit the proliferation of Müller cells when cultured in vitro. The efficacy of this inhibition was found to be dependent on both the concentration of the drug and the duration of the stimulation. Higher concentrations of the drug and longer stimulation times resulted in a weaker ability of the cells to proliferate. Additionally, PTX also induces apoptosis in Müller cells, with increased drug concentrations and longer stimulation times leading to higher apoptosis rates. Flow cytometry analysis demonstrates that PTX arrests Müller cells in the G2-M phase of the cell cycle. Moreover, there is a distinct change in cell morphology, with a shift from the typical appearance characterized by clear and slender fibrous structures to a rounder morphology, accompanied by a significant decrease in cell numbers. Further, our findings reveal that there is a transient increase in the expression of cytoinflammatory factors following drug treatment compared to the control group. However, discontinuation of drug stimulation can alleviate this heightened expression. In treated cells, the expression of the CA XIV protein is upregulated compared to the control group, while the expression of vascular endothelial growth factor(VEGF)is downregulated(P&#x0026;#x003C;0.05). Additionally, the levels of inflammatory factors in the PTX group are significantly higher than those in the control group(P&#x0026;#x003C;0.05), suggesting that PTX has the potential to disrupt the retinal barrier function.CONCLUSION: PTX affects the proliferation and apoptosis of Müller cells, with the effects dependent on stimulation duration and drug concentration. In addition, PTX blocks the Müller cell cycle at the G2-M phase and alters cell morphology, leading to a transient upregulation of inflammatory factors and affecting the integrity of the retinal barrier. These findings indicate the potential toxicity of the antitumor drug PTX to the retina.

Adolescent Gitelman syndrome:a case report and literature review / 中国综合临床

Objective:To explore the clinical characteristics and genetics of a Chinese patient with Gitelman syndrome (GS) and improve the awareness and diagnosis of GS among clinicians.Methods:Retrospectively analyzed the GS patient's clinical feature, laboratory examination, diagnosis, treatment and literature review admitted to Hebei General Hospital in September 2022.Results:A twelve-year-old boy was admitted to our department due to weakness of lower limbs. Laboratory tests after admission showed hypokalemia, hypomagnesemia, hypocalcemia and metabolic alkalosis. Genetic testing showed tow compound heterozygous mutations in the SLC12A3 gene (c.1456G>A and c.634G>A), which ultimately diagnosed as GS. The patient is on the mend and allowed to leave the hospital after treated by potassium supplement.Conclusion:The rate of leak diagnosis is high. Genetic testing should be undergo earlier if the patients suspected GS.

Tetrahydroxy stilbene glycoside ameliorates neuroin-flammation for Alzheimer's disease via cGAS-STING / 中国药理学与毒理学杂志

OBJECTIVE Alzheimer's disease(AD)is the most common neurodegenerative disease worldwide.Neuroinflammation is a potential target for the patients with AD.It is attributed to activated microglia and the release of various inflammatory mediators from infec-tion,ischemia and toxin accumulation.Accumulating evi-dence has indicated that the cGAS-STING pathway driven neuroinflammation in neurological disease.TSG is a main natural active ingredient that derived from polyg-onum multiflorum.Previous research from our group found that TSG has beneficial effects of anti-aging,anti-inflammatory action and improving memory function in APP/PS1 transgenic AD mice.Here,we investigated the effects of TSG on cognitive impairment and neuroinflam-mation in APP/PS1-AD mice and explore the underly-ing mechanism by which TSG ameliorates memory func-tion in the cGAS-STING-mediated inflammatory response.METHODS The Morris water mace test and the novel object recognition test were performed to test the effects of TSG on spatial learning and cognitive and memory abil-ity in APP/PS1 double transgenic AD mice model.In addi-tion,real-time quantitative PCR,Western blotting,ELISA analysis,and flow cytometry to examine gene and pro-tein expression of cGAS-STING related pro-inflammatory cytokines and chemokines.Statistical analyses were ana-lyzed using the SPSS 25.0 package by analysis of vari-ance(ANOVA).Neuman-Keuls or Tukey's multiple-com-parisons test were conducted as ANOVA justified post hoc comparisons between group means.RESULTS We demonstrated that AD transgenic mice exhibited cognitive deficits accompanied by the elevated serum and brain inflammation.The expressions of serum inflammatory cytokines and the activation of microglia in cerebral cor-tex and hippocampus were suppressed after TSG treat-ment,which was probably attributable to the decrease of cyclic GMP-AMP synthase(cGAS)and stimulator of interferon genes(STING)triggered immune response.Additionally,the data showed that TSG treatment reduced the expression level of inflammatory cytokines(IL-1β,TNF-α,IFN-β,IFN-α)in microglial cells BV2 primed with LPS and IFN-γ.CONCLUSION TSG implicated the health benefits in preventing cognitive disorders by inhib-iting neuroinflammation via cGAS-STING signalling path-way in AD.

Cornel iridoid glycoside alleviates microglia-mediated inflammatory response via NLRP3/calpain pathway / 中国药理学与毒理学杂志

OBJECTIVE Vascular dementia(VaD)is associated with cerebral hypoperfusion,which results in long-term cognitive impairment and memory loss.Neuroin-flammation is an important mechanism of vascular demen-tia.Cornel iridoid glycoside(CIG)is the major active con-stituent isolated from the ripe fruit of Cornus officinalis.Previous studies have shown that CIG enhances neuro-logical function in VaD rats.In the present research,we attempted to clarify the molecular processes underlying the role of CIG on neuroinflammation in VaD.METHODS In vivo,we created a chronic cerebral ischemia rat model by ligation of the bilateral common carotid arteries(2VO).The rats were divided into sham operation,2VO,2VO + CIG(60 and120 mg·kg-1·d-1),and 2VO+ butylphthalide(100 mg·kg-1·d-1)groups and then treated rats with differ-ent concentrations of CIG.In vitro,BV2 microglia cells were induced with bacterial lipopolysaccharide(LPS)and interferon-γ(IFN-γ)to construct the model of microglias with analog neuroinflammation.Histopathology and biel-schowsky silver staining were used to detect myelin integrity and neuronal loss.Immunofluorescence was used to observe changes in microglia.Magnetic Luminex Assay was used to detect changes in inflammatory fac-tors.Western blotting,ELISA or calpain activity assay was used to measure the expression and activity of cal-pain,as well as the expression of NLRP3 inflammasome protein.Furthermore,NLRP3 overexpressing cells were used to further elucidate the potential anti-inflammatory molecular mechanism of CIG.RESULTS ① CIG improved neuronal impairment in the brain of 2VO rats.②CIG increased white matter(WM)integrity in 2VO rats.③ CIG reduced microglia inflammatory response in the cortex and hippocampus of 2VO rats.④ CIG inhibited calpain activity in the cortex and hippocampus of 2VO rats.⑤ CIG exerted anti-inflammatory effects on BV2 cells stimulated by LPS and IFN-γ.⑥ CIG Inhibited the expression and activity of calpain in LPS/IFN-γ-activated BV2 cells.⑦ The main component of CIG had a weak binding force to calpain1.⑧ CIG inhibited the activation of the NLRP3 inflammasome.⑨CIG reduced the activity of calpain induced by NLRP3 overexpression.CONCLU-SION CIG inhibits microglial polarization into a proinflam-matory state by attenuating the assembly of the NLRP3 inflammasome and calpain activation,thus reducing brain inflammation,WM injury,and the loss of neurons.To sum up,the present study suggests that CIG inhibits neuroinflammation.The NLRP3/calpain pathway may be the main pathway by which CIG protects against neuroin-flammation.

Expression of HLA-G in the peripheral blood and cancerous tissues of patients with papillary thyroid cancer / 中华内分泌外科杂志

Objective:To examine the expression of human leukocyte antigen G (HLA-G) in the peripheral blood and cancerous tissues of patients with papillary thyroid carcinoma (PTC) .Methods:The expression of soluble HLA-G (sHLA-G) in the peripheral blood of 50 individuals with PTC (PTC group) , 25 patients with benign thyroid tumors (BTT group) from Department of Thyroid and Breast Surgery, Beilun branch of the First Affiliated Hospital of Zhejiang University and 20 healthy controls (healthy control group) from physical examination center was assessed by ELISA. Immunohistochemical examination of HLA-G levels was also performed on tissue specimens from patients in the PTC and BTT groups, and their correlation with clinicopathological features of thyroid cancer was analyzed. SPSS 19.0 was used for statistical analysis. The measurement data of normal distribution were tested by two independent samples t test. Chi square test was used to compare the rates between the two groups. Results:The sHLA-G expression in peripheral blood was 21.33 (±5.54) , 22.73 (±4.99) , and 18.29 (±4.43) ng/mL in the preoperative PTC, BTT, and healthy control groups, respectively. Compared to the healthy group, sHLA-G levels were considerably higher in the PTC and BTT groups, with statistically significant differences (totally P < 0.05) . There was no significant difference in statistically sHLA-G levels between the BTT and PTC groups ( P > 0.05) . The positive HLA-G expression rate in PTC tissues was 78% (39/50) . There was no evidence of HLA-G expression in common tissues adjacent to PTC. HLA-G was not expressed in benign tumors. HLA-G was linked with the PTC tumor diameter, and the rate of positive expression was considerably greater with tumor diameters >1 cm than with those ≤1 cm ( P<0.05) . The rate of HLA-G positive expression was not significantly correlated with sex, age, multiple foci, extra-glandular invasion, metastasis of lymph nodes, or the TNM stage in PTC individuals ( P > 0.05) . Conclusions:HLA-G is significantly expressed at high levels in PTC tissues, is correlated with the tumor diameter, and may probably have a significant role in this disease. Peripheral blood sHLA-G may be associated with thyroid tumorigenesis, and its value in PTC requires further verification.

Clinical effect of Huangqi Chifeng Decoction combined with modified Duhuo Jisheng Decoction in the treatment of ischemic stroke during recovery / 国际中医中药杂志

Objective:To evaluate the clinical curative effect of Huangqi Chifeng Decoction combined with modified Duhuo Jisheng Decoction on patients with ischemic stroke (IS) during recovery.Methods:Prospective cohort study. A total of 220 patients with IS during recovery who met inclusion criteria in the First People's Hospital of Dongcheng District in Beijing, were enrolled and divided into control group ( n=110) and observation group ( n=110) by random number table method between January 2015 and July 2020. The control group was given basic treatment, while observation group was given Huangqi Chifeng Decoction combined with modified Duhuo Jisheng Decoction. All were treated for 1 month. Before and after treatment, Traditional Chinese Medicine (TCM) syndromes were scored. The activities of daily living were evaluated by Barthel index. The quality of life was evaluated by stroke specific quality of life scale (SS-QOL). The severity of neurological impairment was evaluated by National Institute of Health Stroke Scale (NIHSS). The functional recovery of stroke was evaluated by modified Rankin scale (mRS). The adverse reactions during treatment were observed and recorded. Results:After treatment, scores of TCM syndromes, mRS and NIHSS in observation group were significantly lower than those in the control group ( t=21.87, 4.66, 12.06, P<0.01), while scores of Barthel index and SS-QOL were significantly higher than those in the control group ( t=14.13, 5.80, P<0.01). During treatment, there were no obvious adverse reactions in either group. Conclusion:Huangqi Chifeng Decoction combined with modified Duhuo Jisheng Decoction can improve clinical symptoms and nerve function in patients with IS during recovery, which is beneficial to improve outcomes and quality of life.