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.

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.

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.

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.

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<0.05), the CMT in both groups was lower than that before the treatment(P<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<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<0.001). In the injection group, only blurred vision was improved(P<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<0.001).CONCLUSIONS: The Yishen Yanggan Mingmu formula combined with intravitreal anti-VEGF drug injection is effective in the treatment of wARMD.

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.

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.

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.

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.

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.

Application of single incision plus one port laparoscopic surgery in radical right hemicolon cancer surgery / 中华胃肠外科杂志

Objective: To investigate the feasibility and advantages of the SILS+1 technique in the radical right hemicolectomy, by comparing the short-term efficacy, postoperative recovery of intestinal function, and stress and inflammatory response of patients with right-sided colon cancer undergoing the conventional 5-hole laparoscopic technique or the single incision plus one port laparoscopic surgery (SILS+1). Methods: A retrospective cohort study was performed. Thirty-five patients with right-sided colon cancer undergoing SILS+1 surgery at Department of Gastrointestinal Surgery of Fujian Cancer Hospital from January 2018 to September 2020 were enrolled in the SILS+1 group. Then a total of 44 patients who underwent completely 5-hole laparoscopic right hemicolectomy at the same time were selected as the conventional laparoscopic surgery (CLS) group. The intraoperative observation indexes (operative time, intraoperative blood loss, and incision length) and postoperative observation indexes (time to ambulation after surgery, time to flatus, pain score in the first 3 days after surgery, hospitalization days, number of lymph node dissections, postoperative complication morbidity, and postoperative total protein, albumin and C-reaction protein) were compared between the two groups. Results: There was no conversion to laparotomy or laparoscopic-assisted surgery in both groups. All the patients successfully completed radical right hemicolectomy under total laparoscopy. There were no statistically significant differences in gender, age, body mass index or tumor stage between the two groups (all P>0.05). Compared with the CLS group, the SILS+1 group had shorter incision length [(5.1±0.6) cm vs. (8.5±4.1) cm, t=4.124, P=0.012], shorter time to the first ambulation (median: 27.6 h vs. 49.3 h, Z=4.386, P=0.026), and shorter time to the first flatus (median:42.8 h vs. 63.2 h, Z=13.086, P=0.012), lower postoperative pain score [postoperative 1-d: 2.0 ± 1.1 vs. 3.6 ± 0.9; postoperative 2-d: 1.4 ± 0.2 vs. 2.9±1.4; postoperative 3-d: 1.1 ± 0.1 vs. 2.3±0.3, F=49.128, P=0.003), shorter postoperative hospital stay [(9.1 ± 2.7) d vs. (11.2 ± 2.2) d, t=3.267,P=0.001], which were all statistically significant (all P<0.05). On the second day after surgery, as compared to CLS group, SILS+1 group had higher total protein level [(59.7±18.2) g/L vs. (43.0±12.3) g/L, t=2.214, P=0.003], higher albumin level [(33.6±7.3) g/L vs. (23.7±5.4) g/L, t=5.845, P<0.001], but lower C-reactive protein level [(16.3 ± 3.1) g/L vs. (63.3 ± 4.5) g/L, t=4.961, P<0.001], which were all statistically significant. There were no significant differences in the operative time, intraoperative blood loss, number of harvested lymph node, number of metastatic lymph node, and postoperative complication morbidity (all P>0.05). Conclusions: The SILS+1 technique has good operability and potential for popularization. Under the premise of radical resection, this technology not only reduces incision number and postoperative physical pain, but also speeds up postoperative recovery and shortens hospital stay.

Research advances in assessment tools for feeding problems in children / 中国当代儿科杂志

As one of the most important non-nutritional factors associated with children's growth and development, feeding problems in children are getting more and more attention from medical professionals and guardians. The evaluation of feeding problems has developed from the single-factor and descriptive research in the past to the multi-factor and analytical research at present, and thus a good quantitative analysis system is increasingly important for researchers. However, the development of localized quantitative analysis tools remains a weak link in this field. Therefore, it is a research hotspot to develop child feeding assessment scales and questionnaires with high reliability, validity, and operability in combination with China's cultural background and eating habits and provide effective assessment tools for feeding problems in Chinese children. Through classification based on research mode and screening, this article reviews the research findings in the field of child feeding, so as to provide a basis for future research.

[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.

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.

Application of Chen's pancreaticojejunostomy technique in laparoscopic pancreaticoduodenectomy (116 cases report) / 中华外科杂志

To investigate the safety and feasibility of longitudinal transpancreatic U-sutures invaginated pancreatojejunostomy (Chen's pancreaticojejunostomy technique) in laparoscopic pancreaticoduodenectomy (LPD). Clinical data of 116 consecutive patients who underwent LPD using Chen's pancreaticojejunostomy technique in Hunan Provincial People's Hospital from May 2017 to December 2018 were retrospectively analyzed. Among these patients, 66 were males and 50 were females. The median age was 58 years old (32-84 yeas old). All 116 patients underwent pure laparoscopic whipple procedure with Child reconstruction method, using Chen's pancreaticojejunostomy technique. The intraoperative and postoperative data of patients were analyzed. All 116 patients underwent LPD successfully. The mean operative time was (260.3±33.5) minutes (200-620 minutes). The mean time of pancreaticojejunostomy was (18.2±7.6) minutes (14-35 minutes). The mean time of hepaticojejunostomy was (14.6±6.3) minutes (10-25 minutes). The mean time of gastrojejunostomy was (12.0±5.5) minutes (8-20 minutes). The mean estimated blood loss was (106.0±87.6) ml (20-800 ml). Postoperative complications were: 11.2%(13/116) of cases had postoperative pancreatic fistula (POPF), including 10.3% (12/116) of biochemical fistula and 0.9%(1/116) of grade B POPF, no grade C POPF occurred; 10.3%(12/116) had gastrojejunal anastomotic bleeding; 3.4%(4/116) had hepaticojejunal anastomotic fistula; 3.4%(4/116) had delayed gastric emptying; 4.3% (5/116) had localized abdominal infection; 12.1%(14/116) had pulmonary infection; postoperative mortality were 0(0/116) and 1.7%(2/116) within 30 days and 90 days, respectively. One patient died of massive abdominal bleeding secondary to Gastroduodenal artery pseudoaneurysm rupture, the other patient died of extensive tumor recurrence and metastasis after surgery. Chen's pancreaticojejunostomy technique is safe and feasible for LPD.It is an option especially for surgeons who have not completed the learning curve of LPD.

Simultaneous Determination of Pyrrolidine Alkaloids and Their Nitrogen Oxides in Farfarae Flos by UPLC-MS/MS / 中国实验方剂学杂志

<b>Objective::To establish an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the simultaneous determination of 15 pyrrolidine alkaloids (PAs) and their nitrogen oxides, and determine the content of the 15 PAs in the 15 batches of Farfarae Flos samples obtained from different sources, in order to understand the distribution status of these 15 PAs in Farfarae Flos from different sources, and provide relevant references for the safe and rational use of this medicinal materials. <b>Method::The method was achieved by Agilent Eclipse Plus C₁₈ column (3.0 mm×150 mm, 1.8 μm) using a mobile phase made up of 0.05%formic acid and 2.5 mmol·L^-1 ammonium formate in water (A)-0.05%formic acid and 2.5 mmol·L^-1 ammonium formate in methanol(B). The flow rate and the injection volume were 0.4 mL·min^-1 and 2 μL, respectively. The column temperature was 40 ℃. The instrument was Agilent 1290-6470 QQQ ultra high performance liquid chromatography-triple quaternary bar mass spectrometer. The components were detected in multiple reaction monitoring mode by mass spectrometry with ionizationmode of ESI⁺. The content of the components measured in the samples was calculated by using the external standard method, and the difference between samples was analyzed based on RSD of different components. <b>Result::The established method had a high sensitivity and good separation degree. The results of methodological investigation met the requirements. The results showed that all of the 15 batches of Farfarae Flos contained PAs and their nitrogen oxides. These PAs had almost the same types of structure. There were significant differences in the content and distribution of PAs in Farfarae Flos obtained from different sources. <b>Conclusion::In general, Farfarae Flos contains pyrrolidine alkaloids and their nitrogen oxides. Senkirkine with a significant hepatotoxicity is the main compound. The content determination of PAs will provide scientific fundaments for the safe and effective use of Farfarae Flos.

Status of content analysis of pyrrolizidine alkaloids in food and herbs / 中国中药杂志

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.