Quantitative Proteomics and Metabolomics of Culture Medium from Single Human Embryo Reveal Embryo Quality-Related Multiomics Biomarkers.

An effective tool to assess embryo quality in the assisted reproduction clinical practice will enhance successful implantation rates and mitigate high risks of multiple pregnancies. Potential biomarkers secreted into culture medium (CM) during embryo development enable rapid and noninvasive methods of assessing embryo quality. However, small volumes, low biomolecule concentrations, and impurity interference collectively preclude the identification of quality-related biomarkers in single blastocyst CM. Here, we developed a noninvasive trace multiomics approach to screen for potential markers in individual human blastocyst CM. We collected 84 CM samples and divided them into high-quality (HQ) and low-quality (LQ) groups. We evaluated the differentially expressed proteins (DEPs) and metabolites (DEMs) in HQ and LQ CM. A total of 504 proteins and 189 metabolites were detected in individual blastocyst CM. Moreover, 9 DEPs and 32 DEMs were identified in different quality embryo CM. We also categorized HQ embryos into positive implantation (PI) and negative implantation (NI) groups based on ultrasound findings on day 28. We identified 41 DEPs and 4 DEMs associated with clinical implantation outcomes in morphologically HQ embryos using a multiomics analysis approach. This study provides a noninvasive multiomics analysis technique and identifies potential biomarkers for clinical embryo developmental quality assessment.

[Status of content analysis of pyrrolizidine alkaloids in food and herbs].

Pyrrolizidine alkaloids(PAs) are a group of naturally occurring alkaloids with a pyrrolizidine skeleton which can be found in about 3% of the world's flowering plants. It is notorious that PAs are cause the hepatoxic and genotoxic-carcinogenic effects by taking PA-containing herbs, food and dietary supplements. In order to control the poisoning caused by PAs, European Medicines Agency has set a limit of intake of PAs from herbal medicinal products at 0.007 µg of 1,2-unsaturated PAs/kg body weight. Nonetheless, a systematic overview of the amount of PAs in the herb has not been provided. Therefore, this paper is to systematically review the current status of PAs content analysis of herbal medicines and foods reported in the literature, and to provide theoretical and experimental support for the safety risk assessment and control of PAs in Chinese herbal medicines.

Impact of tumour size on prognosis of upper urinary tract urothelial carcinoma after radical nephroureterectomy: a multi-institutional analysis of 795 cases.

OBJECTIVE: To evaluate the prognostic impact of tumour size on survival outcomes in upper urinary tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). PATIENTS AND METHODS: Data on 795 patients treated with RNU for UTUC from seven centres were retrospectively analysed with focus on tumour size. Clinicopathological features and relevant prognostic factors were compared between patients with tumours ≤3.0 cm and those with tumours >3.0 cm in size. The primary endpoints were cancer-specific survival (CSS), disease recurrence-free survival (RFS) and overall survival (OS). RESULTS: At a median follow-up of 32 months, 313 (39.4%) patients died from UTUC, 321 (40.4%) developed cancer recurrence, and 359 (45.1%) died from all causes. Tumour size >3.0 cm was associated with unfavourable clinicopathlogical features. Kaplan-Meier analysis showed that tumour size was significantly correlated with worse CSS, RFS and OS (all P < 0.001). Multivariate analysis showed that tumour size was an independent predictor of CSS (hazard ratio [HR] 2.296; P < 0.001), RFS (HR 2.193; P < 0.001) and OS (HR 2.417; P < 0.001). CONCLUSIONS: Tumour size >3.0 cm was a significant predictor of CSS, RFS and OS after RNU for patients with UTUC. Further studies are warranted before tumour size is included in risk prediction tools.

The pulmonary biopharmaceutics and anti-inflammatory effects after intratracheal and intravenous administration of Re-Du-Ning injection.

BACKGROUND: Re-Du-Ning injection (RDN) is a renowned heat-clearing traditional Chinese medicine for the treatment of respiratory diseases owing to its anti-inflammatory effects. However, very little is known about the pulmonary distribution and lung exposure-efficacy relationships. This study aimed to investigate the pulmonary distribution and biopharmaceutics concerning lung penetrability and affinity and the local anti-inflammatory effects after intravenous and pulmonary administration of RDN. METHODS: Two iridoids and seven phenolic acid components were selected as the chemical markers in RDN. The in vitro pulmonary distribution and biopharmaceutics were conducted by evaluating the binding and disassociation kinetics of chemical markers in lung tissue explants whereas the in vivo evaluation was performed by determining the time-dependent concentrations of chemical markers in plasma, lung epithelial lining fluid (ELF), lung tissues and immune cells in the ELF after intratracheal and intravenous administrations of RDN. The inhibitory effects on tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production were used to evaluate the anti-inflammatory effect of RDN on lung tissues in vitro and on mice with LPS-induced lung inflammation. RESULTS: The chemical markers of RDN exhibited excellent lung penetrability but poor lung affinity in vitro and in vivo. After intravenous administration, the chemical markers appeared to rapidly penetrate through the lung tissue to reach the ELF, leading to markedly higher drug exposure to ELF and immune cells in the ELF than to lung tissues. Compared to intravenous injection, the intratracheal instillation of RDN increased drug exposure to lung tissue and immune cells in the ELF by up to > 80-fold, leading to improved anti-inflammatory potency and prolonged duration of action. CONCLUSION: The drug exposure to immune cells in the ELF was correlated with the lung-targeted anti-inflammatory effects of RDN and pulmonary delivery has the potential to replace intravenous injection of RDN for the treatment of respiratory diseases.

The pulmonary pharmacokinetics and anti-inflammatory effects after intratracheal and intravenous administration of Chuankezhi injection.

BACKGROUND: Chuankezhi injection (CKZ) is a traditional Chinese medicine for the treatment of respiratory diseases and has been often used off-label as a nebulization therapy. However, little is known about the aerosolization performance and pulmonary fate of the inhaled CKZ. This study aimed to evaluate the aerodynamic characteristics of nebulizer generated aerosols and to compare the properties of pharmacokinetics, lung distribution and anti-inflammation effects of CKZ after intratracheal and intravenous administration. METHODS: The nebulization performance was evaluated in vitro based on the aerodynamic particle size distribution and aerosol output. The concentrations of epimedins A, B, C and icariin, the main active ingredients of CKZ, in plasma, bronchoalveolar lavage fluids (BALF) and lung tissues were measured by LC-MS/MS analysis. The pulmonary anti-inflammatory efficacy were tested using LPS-induced pulmonary inflammation mice model as indicated by the total cells counts, and the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in BALF. RESULTS: The aerosols of CKZ generated by a commercial nebulizer showed excellent aerodynamic properties and delivery output. Following intratracheal instillation of CKZ, epidemins A, B and C, and icariin, were absorbed into the bloodstream with the mean absorption time varying from 101.8 min to 271.8 min, and their absolute bioavailabilities ranging from 26.4 % to 104 %. The instillation of CKZ increased the lung to plasma concentration ratios by 25.5-718 folds compared to intravenous administration, leading to improved and prolonged local anti-inflammatory effects. CONCLUSION: Nebulization therapy of CKZ could be a promising alternative to the injectable counterpart.

Comparison of plasma and pulmonary availability of chlorogenic acid, forsythiaside A and baicalin after intratracheal and intravenous administration of Shuang-Huang-Lian injection.

ETHNOPHARMACOLOGICAL RELEVANCE: The off-label nebulization of Shuang-Huang-Lian (SHL) injection is often utilized to treat respiratory tract infections in China. However, the pulmonary biopharmaceutics of SHL was generally unknown, limiting the rational selection of therapeutic dose and dose frequency. AIM OF THE STUDY: To characterize the size distribution of nebulized aerosols and to compare the pharmacokinetics and the lung distribution of three chemical makers of SHL, chlorogenic acid (CHA), forsythiaside A (FTA) and baicalin (BC), after intratracheal and intravenous administration of SHL to rats. MATERIALS AND METHODS: The droplet size distribution profiles over nebulization process were dynamically monitored using a laser diffraction method whereas the levels of CHA, FTA and BC in plasma, lung tissues and bronchoalveolar lavage fluids (BALF) were determined by a validated LC-MS/MS assay. The pulmonary anti-inflammatory efficacy was evaluated using a lipopolysaccharide (LPS) induced lung inflammation model as indicated by the level of tumor necrosis factor-α (TNF-α) in BALF. RESULTS: The nebulization of SHL showed good inhalability and allowed the aerosols to reach the upper or lower respiratory tract dependent on the performance of selected nebulizers. Following intratracheal administration of SHL at different doses, CHA, FTA and BC were absorbed into the bloodstream with the mean absorption time being 67.5, 63.5 and 114 min, respectively, rendering mean absolute bioavailabilities between 42.4% and 61.4% roughly independent of delivered dose. Relative to the intravenous injection, the intrapulmonary delivery increased the lung-to-plasma concentration ratios of CHA, FTA and BC by more than 100 folds and markedly improved the lung availability by 563-676 folds, leading to enhanced and prolonged lung retention. The production of TNF-α in BALF was decreased by ~50% at an intratracheal dose of 125 µL/kg SHL to LPS-treated mice. CONCLUSION: The nebulization delivery of SHL is a promising alternative to the intravenous injection for the treatment of respiratory tract infections.

Comparison of pulmonary availability and anti-inflammatory effect of dehydroandrographolide succinate via intratracheal and intravenous administration.

Dehydroandrographolide succinate (DAS) injection, which was approved in China for the treatment of viral pneumonia and upper respiratory tract infections, is often off-label used for nebulization therapy to avoid the adverse drug reactions associated with the injection. However, the aerodynamic properties and pulmonary fate of nebulized DAS was largely uninvestigated. In this study, the main objectives were to evaluate the in vitro aerodynamic deposition profiles of nebulizer generated aerosols and comparatively investigate the local drug availability and anti-inflammatory efficacy of DAS between intratracheal and intravenous dosing. The in vitro evaluation of aerodynamic characteristics and droplet size distribution showed more than 50% aerosol particles with size being <5 µm, allowing the aerosols to reach the lower respiratory tract. Following intratracheal administration, the drug underwent pulmonary absorption into the bloodstream, rendering an absolute bioavailability of 47.3%. Compared to the intravenous delivery, the intratracheal administration dramatically increased the drug availability in the lung tissue in rats by more than 80-fold, leading to an improved and prolonged local anti-inflammatory efficacy in a lipopolysaccharide induced lung injury model in mice. The present results demonstrated that inhalation delivery of DAS is a convenient and effective alternative to intravenous injections.

Research progress of integrated stress response in central nervous system diseases / 中国药科大学学报

@#Abstract: Integrated stress response is an adaptive response produced by eukaryotic cells after intracellular and extracellular stimulation. The activation of integrated stress response inhibits the translation of most proteins, yet it can promote the translation of certain proteins to cope with complex cellular microenvironment changes. A large number of studies have found that in a variety of nervous system diseases, the integrated stress response can be activated by stress signals of disease-related cells and participates in the occurrence and progression of diseases through processes such as learning and memory consolidation, myelin regeneration and synaptic plasticity. This article summarizes the role, mechanism and possible drug targets of integrated stress response in central nervous system diseases and discusses the potential of pharmacological methods to regulate integrated stress response in the treatment of central nervous system diseases, in order to provide reference for pathological research on and drug development for central nervous system diseases.

[Determination of As, Sb, Bi, Cd and Sn in soils and sediments by inductively coupled plasma atomic emission spectrometry after sublimation separation as iodides].

A method was developed for the determination of As, Sb, Bi, Cd and Sn in degrees C, iodides of As, Sb, Bi, Cd and Sn were formed and sublimated from the sample matrix and then extracted by diluted HCl. The prepared solution was determined by ICP-AES. The sample treatment procedure, such as the ratio of NH4 I to sample, and sublimation and extraction conditions, was studied. The instrument determination parameters, including ICP power, Ar gas flow rate, spectral wavelengths, background subtraction, spectral interferences correction and internal standard, were selected and optimized. The established procedure is rapid and simple, the detection limits for the five elements are in the range of 0.01-0.35 microg x g(-1), and the analytical results for soil and sediment reference materials were in good agreement with the reference values.

[Determination of Si, Al and other in biological samples by ICP-AES with fusion with LiBO2 after dry ashing].

An alkaline sample digestion procedure using fusion with lithium metaborate (LiBO2) after dry ashing was developed. Silicon, aluminium and other, a total of 10 elements in different kinds of biological samples, were measured by ICP-AES. The detection limit of this method was 0.15 microg x mL(-1) for Si and 0.03 microg x mL(-1) for Al. The accuracy and precision of the method were demonstrated by analyzing certified reference materials poplar leaves (GBW07604). The precision was less than 3% and the accuracy was -0.03% for Si and -3% for Al. This method was applied to the certification of a series of ten biological reference materials. The results were satisfied.

Reaserch progress of microglial phagocytosis in ischemic stroke / 中国药科大学学报

@#Ischemic stroke is a major disease affecting human health, and its pathological mechanism has not been fully elucidated. Microglia are important immune cells in the central nervous system, and participate in the pathological process of ischemic stroke.Following an ischemic stroke, a surge in activated microglia occurs, migrating and congregating within the afflicted regions.These microglia engulf deceased cells or fragments, releasing inflammatory or nutritive factors, thereby participating in the pathogenesis of ischemic stroke.The phagocytosis of microglia plays an important role in cerebral ischemic injury and rehabilitation. This article summarizes the molecular mechanism of microglial phagocytosis and reviews the research progress of microglial phagocytosis in ischemic stroke, and discusses the diversity and complexity of microglial phagocytosis in cerebral ischemic injury and rehabilitation, so as to provide new ideas for the treatment and drug development of ischemic stroke.

Yishen Yanggan Mingmu formula combined with anti-vascular endothelial growth factor drugs for the treatment of wet age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the clinical efficacy of Yishen Yanggan Mingmu formula combined with anti-vascular endothelial growth factor(VEGF)in the treatment of wet age-related macular degeneration(wARMD).METHODS: A total of 58 patients(58 eyes)with wARMD who were treated in Ningbo Eye Hospital from September 2020 to November 2022 were collected. They were divided into two groups according to randomized digital table: 29 patients(29 eyes)for the combination group and the other 29 patients(29 eyes)for the injection group. The injection group was only given intravitreal injection of conbercept; the combination group was orally administrated with Yishen Yanggan Mingmu formula combined with intravitreal injection of conbercept. The best corrected visual acuity(BCVA), central macular thickness(CMT)and the improvement of traditional Chinese medicine(TCM)syndromes after 3mo of treatment were observed and the clinical efficacy was evaluated.RESULTS: After 3mo of treatment, the total improved effective rate of the combination group(76%)was higher than the rate of the injection group(66%). After the treatment, the BCVA of the two groups was both higher than that before treatment(P&#x003C;0.05), the CMT in both groups was lower than that before the treatment(P&#x003C;0.05), and the improvement of CMT of the combination group was better than the injection group(-155.93±143.79μm vs. -95.36±56.81μm, P&#x003C;0.05). After 3mo of treatment, each kinds of TCM syndrome in the combination group were significantly improved compared with those syndromes before the treatment(P&#x003C;0.001). In the injection group, only blurred vision was improved(P&#x003C;0.05). After the treatment, the scores of dizziness and insomnia, soreness and weakness of waist and knees, paleness and cold limbs, dry eyes and fatigue in the combination group were significantly lower than the injection group(P&#x003C;0.001).CONCLUSIONS: The Yishen Yanggan Mingmu formula combined with intravitreal anti-VEGF drug injection is effective in the treatment of wARMD.

A case report of synchronous triple cancers in the urinary and male reproductive system / 中华泌尿外科杂志

Multiple primary cancers are rare, and synchronous multiple primary cancers occurring in the urinary system are even rarer. This article reported a male patient with synchronous multiple cancers in the urinary and male reproductive system. The patient was admitted due to left hip joint pain and the possibility of malignancy in the prostate and kidney metastasis was not ruled out. Biopsy of the prostate and right kidney revealed prostate adenocarcinoma with a Gleason score of 5+ 5 and clear cell renal cell carcinoma, respectively. Because an MRI indicated a bladder lesion, transurethral resection of the bladder tumor was performed, which revealed low-grade papillary urothelial carcinoma of the bladder. After seven months of combined chemotherapy, the patient died 16 months after surgery due to multiple metastases of the tumors throughout the body.

Guideline for clinical comprehensive evaluation of Chinese patent medicine (2022 version) / 中国中药杂志

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.

Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial / 中华医学杂志(英文版)

BACKGROUND@#LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.@*METHODS@#We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels.@*RESULTS@#On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]).@*CONCLUSION@#LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT04563936.

The role of p75 neurotrophin receptor in neurodegenerative diseases / 中国药理学通报

Recently p75 neurotrophin receptor (p75NTR) has been found to play a critical role in the pathology of neurodegen¬erative! diseases including Alzheimer's disease (AD) , Parkin¬son' s disease ( PI)), Huntington's disease ( HI)) , amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS).This arti¬cle reviews the research progress of p75NTR in regulating neuron apoptosis, axon degeneration and cognitive impairment, explo¬ring the application of p75NTR as a potential therapeutic target for the treatment of neurodegenerative diseases.

Comparison of 18F-PSMA PET/CT and mpMRI in the diagnosis of pelvic lymph node metastasis of prostate cancer / 中华泌尿外科杂志

Objective:To compare the diagnostic efficacy of 18F-prostate specific membrane antigen (PSMA)-1007 PET/CT and mpMRI in the diagnosis of pelvic lymph node metastasis of prostate cancer (PCa). Methods:The clinical data of 30 patients who underwent 18F-PSMA-1007 PET/CT and mpMRI examinations in Sichuan Cancer Hospital from November 2018 to April 2021 were analyzed. The average age was (68.4±6.4) years old. The preoperative total PSA was 45.70(16.07, 100.00)ng/ml. Among 30 patients, 14 cases were found lymph node positive by PET/CT and 7 cases were found lymph node positive by mpMRI.Combined with the two preoperative imaging methods and the patient's PSA level, there was 1 patient in stage T 1, 20 patients in stage T 2, 6 patients in stage T 3, and 3 patients in stage T 4. Twenty-nine cases were classified as high risk group and one case was in moderate risk group.All 30 patients underwent laparoscopic radical prostatectomy and enlarged pelvic lymph node dissection (ePLND). According to the postoperative pathological results, the sensitivity, specificity, positive predictive value and negative predictive value of the two imaging techniques for the diagnosis of PCa pelvic lymph node metastasis were calculated, and the consistency of the two imaging techniques for the postoperative pathological results was observed by Kappa test. Results:All the 30 patients were confirmed to be PCa by postoperative pathology, among which 10 patients were positive for pelvic lymph node biopsy. The sensitivity, specificity, positive predictive value and negative predictive value of 18F-PSMA-1007 PET/CT for pelvic lymph node metastasis were 100.0% (10/10), 80.0% (16/20), 71.4%(10/14) and 100.0%(16/16) respectively, and Kappa value was 0.727. The sensitivity and specificity of mpMRI were 70.0% (7/10) and 100.0% (20/20), the positive and negative predictive values were 100.0% (7/7) and 87.0%(20/23)respectively, and the Kappa value was 0.757. The P values of sensitivity, specificity, positive predictive value and negative predictive value between the two imaging methods were 0.18, 0.07, 0.30, <0.01, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of 18F-PSMA-1007 PET/CT in diagnosing the number of pelvic lymph node metastasis were 100%(28/28), 98.2% (373/380), 80.0% (28/35) and 100.0%(373/373), respectively. The sensitivity, specificity, positive predictive value and negative predictive value of mpMRI in diagnosing the number of pelvic lymph node metastasis were 78.6% (22/28), 100.0% (380/380), 100.0% (22/22) and 98.4%(380/386), respectively. The P values of the sensitivity, specificity, positive predictive value and negative predictive value of lymph node detection by the two imaging methods were all <0.01, and the differences were statistically significant. Conclusions:The sensitivity and negative predictive value of 18F-PSMA-1007 PET/CT for the detection of positive lymph node were higher than mpMRI. The specificity and positive predictive value of mpMRI in detecting positive lymph node metastasis were higher than 18F-PSMA-1007 PET/CT examination.

The pulmonary pharmacokinetics and anti-inflammatory effect of anemoside B4 after intratracheal and intravenous administration / 药学学报

Anemoside B4 (B4), a main triterpenoid saponin from a traditional Chinese medicine plant, Pulsatilla chinensis, is a novel anti-inflammatory agent for protection from acute lung injury. We investigated the pulmonary availability and anti-inflammatory efficacy of B4 after intratracheal and intravenous dosing with a view to evaluating the suitability of inhalation delivery. All animal studies were performed under the guidelines approved by the Animal Care and Use Committee of Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences (Approval No: SLXD-20181113046). In vitro evaluation of the aerodynamic characteristics and droplet size distribution showed that the aerosols generated by a commercially available nebulizer were well deposited in the respiratory tract. Following intratracheal administration, B4 underwent pulmonary absorption into the bloodstream, rendering an absolute bioavailability of 103%. Compared to intravenous delivery, intratracheal administration dramatically increased the drug availability in lung tissue of rats by more than 1 000-fold, leading to improved and prolonged concentrations of B4 in lung tissue up to 48 h. In addition, the intratracheal administration of B4 resulted in dose-dependent and prolonged anti-inflammatory efficacy in a lipopolysaccharide (LPS)-induced lung injury model in mice. The present results demonstrate that inhalation delivery of B4 is a promising approach to treat pulmonary inflammation with once-daily dosing.

Regulation effect of endoplasmic reticulum stress and unfolded protein response activation on skeletal muscle fiber immune behavior / 解剖学报

Objective To investigate the regulatory effects of activated endoplasmic reticulum stress（ERS） and unfolded protein response（UPR） on the immune behavior of the stressed muscle fibers in inflammatory environments induced by interferon-γ（IFN-γ）. Methods The myogenic precursor cells（MPCs） of C57 BL/6 mice cultured in vitro were differentiated into multinucleated myogenic tubes by horse serum and then to set up: 1. Control group; 2. IFN-γ group; 3. Tunicamycin group; 4. Thapsigargin group; 5. IFN-γ and 4-phenylbutyrate（4-PBA） combined treatment group; 6. IFN-γ, TG and 4-PBA combined treatment group; 7. IFN-γ and 4μ8 c combined treatment group; 8. IFN-γ, TG and 4μ8 c combined treatment group; 9. IFN-γ and GSK2606414 combined treatment group; 10. IFN-γ, TG and GSK2606414 combined treatment group. The level of myokines gene was detected by Real-time PCR. The expression of UPR key molecules including eukaryotic intiatio factor 2α（eIF2α）, inositol requrring enzyme 1α（IRE1α） and activating transcription factor 6（ATF6） in muscle fibers was observed by immunofluorescence. Western blotting was used to detect immune molecules related to muscle cells, myokines and key molecules of UPR. Luminex analyzed the levels of pro-inflammatory myokines in muscle fibers. Results The expression of H-2 Kb, H2-Ea, Toll like receptor 3（TLR3）, p-eIF2α and p-IRE1α were up-regulated in IFN-γ induced inflammatory environment. The expression of H-2 Kb, H2-Ea, TLR3 and myokines in the group with UPR inhibitor 4-PBA was down-regulated compared with IFN-γ group, and the expression of these molecules in the group with IRE1α specific inhibitor 4μ8 c was down-regulated compared with the IFN-γ group. The addition of protein kinase R-like endoplasmic eticulum（PERK） specific inhibitor GSK2606414 showed no significant change. Conclusion In IFN-γ induced inflammatory environment, the UPR-IRE1α pathway activates and inhibits the synthesis of muscle fiber immune-related molecules, which further inhibits the muscle fiber mediated immune response and facilitates muscle regeneration.

Research progress of metabotropic glutamate receptor 5 in related central nervous system diseases / 中国药科大学学报

@#As a key component of glutamatergic system, metabotropic glutamate receptor 5 (mGluR5) has been extensively involved in the regulation of physiological processes such as synaptic transmission, synaptic plasticity and synaptic excitation/inhibition balance.Over the past few decades, mGluR5 has been found to be closely related to multiple neurological and psychiatric disorders, thus it is of considerable interest as a drug target in the treatment of such disorders.This review summarizes the structure and distribution of mGluR5, its normal physiological function, its pathological roles in related central nervous system (CNS) diseases, as well as the current status of its drug development, in order to provide reference for further investigation.