Clinical analysis of 11 cases multisystem inflammatory syndrome associated with SARS-CoV-2 Omicron variant infection in children / 中华儿科杂志

Objective: To explore the clinical characteristics, diagnosis, treatment, and follow-up of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 Omicron variant infection. Methods: A retrospective analysis was conducted on clinical data of 11 children with MIS-C, who were admitted to the Department of Pediatrics of Peking University First Hospital from December 2022 to January 2023. Clinical characteristics, treatment, and follow-up of MIS-C were summarized in this study. Results: The 11 cases contained 7 boys and 4 girls, with an age of 4.4 (2.0, 5.5) years on admission. All the patients had fever, with a duration of 7(5, 9) days. Other clinical manifestations included rash in 7 cases, conjunctival hyperemia in 5 cases, red lips and raspberry tongue in 3 cases, lymphadenopathy in 3 cases, and swollen fingers and toes in 2 cases. There were 8 cases of digestive symptoms, 8 cases of respiratory symptoms, and 3 cases of nervous system symptoms. Eight patients had multi-system injuries, and one of them had shock presentation. All 11 patients were infected with SARS-CoV-2 Omicron BF.7 variant. The laboratory examination results showed that all cases had elevated inflammatory indicators, abnormal coagulation function and myocardial damage. Six patients had elevated white blood cell counts, 5 cases had liver function abnormalities, 3 cases had kidney function abnormalities, and 8 cases had coronary artery involvement. All 11 patients received anti-infection treatment, of which 3 cases received only 2 g/kg intravenous immunoglobulin (IVIG), while the remaining 8 cases received a combination of IVIG and 2 mg/(kg·d) methylprednisolone. Among the 8 cases with coronary artery disease, 6 cases received low molecular weight heparin anticoagulation therapy. All patients were followed up in 2 weeks after being discharged, and their inflammatory markers had returned to normal by that time. The 8 cases with coronary artery disease and 3 cases with pneumonia showed significant improvement or back to normal at the 4-week follow-up. All patients had no new complications or comorbidities during follow-up of more than 3 months. Conclusions: MIS-C may present with Kawasaki disease-like symptoms, with or without gastrointestinal, neurological, or respiratory symptoms. Elevated inflammatory markers, abnormal coagulation function, and cardiac injury contribute to the diagnosis of MIS-C. IVIG and methylprednisolone were the primary treatments for MIS-C, and a favorable short-term prognosis was observed during a follow-up period of more than 3 months.

Effects of scutellarin on neuroinflammation in rats with traumatic brain injury by regulating cGAS/STING signaling pathway / 中国药房

OBJECTIVE To investigate the improvement effects and mechanism of scutellarin （Scu） on neuroinflammation in rats with traumatic brain injury （TBI）. METHODS The modified Feeney method was applied to construct TBI rat model. The rats were randomly grouped into TBI group，Scu low-dose group （40 mg/kg），Scu high-dose group （80 mg/kg），cyclic guanylate- adenylate synthase （cGAS） inhibitor group （cGAS inhibitor RU.521，450 μg/kg），with 24 rats in each group. Other 24 rats were included in the sham operation group. The modified neurological deficit score （mNSS） method was applied to assess the neurological function of rats； the brain water content of rats was measured by dry/wet specific gravity method； hematoxylin-eosin and TdT-mediated dUTP nick-end labeling staining were applied to observe the pathological changes and apoptosis of brain tissue in rats； the levels of interferon-β （IFN-β），CXC chemokine ligand-10 （CXCL10），tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in rat brain tissue were detected by enzyme-linked immunosorbent assay； Western blot method was applied to detect the expression of cGAS/interferon gene stimulating protein （STING） signal pathway-related proteins in brain tissue of rats. RESULTS Compared with the sham operation group，the mNSS，brain water content，apoptosis rate，the contents of IFN-β，CXCL10，TNF-α and IL-6，and the relative expressions of cGAS and STING proteins in TBI group increased significantly （P＜0.05）； there were edema，bleeding and pathological damage to neurons in the brain tissue. Compared with TBI group，the above indicators and pathological changes of rats in administration groups were improved significantly （P＜0.05），and the effect of Scu was in a dose- dependent manner （P＜0.05）； however，there was no statistically obvious difference in the above indicators between the Scu high- dose group and the cGAS inhibitor group （P＞0.05）. CONCLUSIONS Scu may alleviate neuroinflammation，reduce brain tissue damage and apoptosis，and promote the recovery of neural function in TBI rats by inhibiting the activation of cGAS/STING signaling pathway.

A Compound Stomachache Capsules Against Prostate Cancer by Targeting Phosphorylated AKT1 / 中国生物化学与分子生物学报

The development of anticancer drugs targeting AKT1 has been reported in a variety of cancers, but there are few related studies on Chinese medicinals targeting AKT1- In this study, Compound stomachache capsules (CSC) was used for inhibiting prostate cancer (PC) cells growth by targeting AKT1 in vitro and in vivo. Through mass spectrum, target prediction and bioinformatics analysis, it is found that 37 of CSC compounds have anticancer activity, and 6 compounds such as (+)-Magnoflorine, 7-hydroxycoumarin may be their main active components against prostate cancer- The results showed that CSC had significant in vitro inhibition on the growth of prostate cancer cells (P<0- 01), and the growth inhibition rate of PC3 cells reached about 35% at 80 μg/ mL- CSC also increased ROS production, and significantly promoted apoptosis (P <0- 01) and G

Pharmacotherapy of patients with left ventricular assist devices / 中国临床药理学与治疗学

Left ventricular assist devices (LVAD) are increasingly used in patients with end-stage heart failure. Devices significantly affect patient physiology, leading to unique complications and different drug treatment strategies. The pharmacist is an integral part of a multidisciplinary team and has the responsibility to help patients use their medicines safely and appropriately. It is important to anticipate common postoperative complications and prepare appropriate treatments for them. This article reviews the current guidelines and research literature on the management of pharmacotherapy in patients with LVAD, integrates clinical research practice, summarizes the medication relevant experience and presents a review.

Longitudinal proteomic investigation of COVID-19 vaccination

Although the development of COVID-19 vaccines has been a remarkable success, the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict. In this study, blood samples were collected from 163 participants who next received two doses of an inactivated COVID-19 vaccine (CoronaVac®) at a 28-day interval. Using TMT-based proteomics, we identified 1,715 serum and 7,342 peripheral blood mononuclear cells (PBMCs) proteins. We proposed two sets of potential biomarkers (seven from serum, five from PBMCs) at baseline using machine learning, and predicted the individual seropositivity 57 days after vaccination (AUC = 0.87). Based on the four PBMC's potential biomarkers, we predicted the antibody persistence until 180 days after vaccination (AUC = 0.79). Our data highlighted characteristic hematological host responses, including altered lymphocyte migration regulation, neutrophil degranulation, and humoral immune response. This study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after COVID-19 vaccination, shedding light on immunization mechanisms and individual booster shot planning.

Analysis of 4 children with DYNC1H1 gene related spinal muscular atrophy with lower extremity predominant 1 / 中华儿科杂志

Objective: To investigate the clinical features and gene variation characteristics of children with dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene associated spinal muscular atrophy with lower extremity predominant (SMALED) 1. Methods: The clinical data of 4 SMALED1 children admitted to Peking University First Hospital from December 2018 to May 2021, who were found to have pathogenic variation of DYNC1H1 gene through genetic testing, except for other genes known to be related to motor retardation, were retrospectively summarized to analyze the phenotype and genotype characteristics. Results: There were 3 males and 1 female. The age of onset was 1 year, 1 day, 1 day and 4 months, respectively. The age of diagnosis was 4 years and 10 months, 9 months, 5 years and 9 months, and 3 years and 1 month, respectively. The clinical manifestations were muscle weakness and muscular atrophy of lower limbs, 2 cases with foot deformity, 1 case with early non progressive joint contracture, 1 case with hip dislocation and 1 case with mental retardation. De novo heterozygous missense variations in DYNC1H1 gene were found in all 4 children. According to the rating of American College of medical genetics and genomics, they were all possible pathogenic and pathogenic variations, with p.R598C, p.P776L, p.Y1109D variations had been reported, and p.I1086R variation had not been reported. Conclusions: For those with unexplained lower limb muscle weakness, muscle atrophy, joint contracture and foot deformity, upper limb motor ability related retention, with or without mental retardation, as well as the motor ability progresses slowly, it is necessary to consider the possibility of SMALED1 and the detection of DYNC1H1 gene when necessary.

Experimental study of transplantation of human umbilical cord mesenchymal stem cells in the treatment of alkali-burned cornea / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the efficacy of transplantation of human umbilical cord mesenchymal stem cells(hUCMSCs)in the treatment of corneal alkali burn in rabbits, and study the infiltration of polymorphonuclear neutrophils(PMNs)and the changes of vascular endothelial growth factor(VEGF)expression.METHODS: Corneal alkali burn models were established in right eyes of 75 healthy Japanese white rabbits, which were divided into three groups(group A, B and C), with 25 rabbits in each group. Group A was treated with amniotic membrane combined with hUCMSCs on the day after corneal alkali burn. Group B was treated with amniotic membrane only. Group C did not give any treatment after corneal alkali burn. At 3, 7, 14, 21 and 28d after corneal alkali burn, the corneal recovery was observed by slit lamp and photographed, the growth of corneal neovascularization(CNV)was scored, and corneal tissue was separated to make pathological sections. PMNs infiltration was observed by hematoxylin-eosin(HE)staining, and the expression of VEGF was determined by immunohistochemical staining.RESULTS: The growth of CNV in group A was much slower than that in group B at 14d after alkali burn. The CNV growth score around lesions of group A was significantly lower than that of group B(P&#x003C;0.05). The quantity of PMNs increased on the 3d with the stromal layer of cornea infiltrated, relatively decreased on the 7d, shown a peak on the 14d, and then decreased gradually. Early infiltration after alkali burn was in the corneal stroma of the lesion area, and the extent of infiltration was equal to the ulcer area at later stage. The cell densities of corneal PMNs in group A and group B were significantly lower than those in group C at all time points after alkali burns(P&#x003C;0.05), and those in group A were significantly lower than group B at 14 and 21d(P&#x003C;0.05). The expression levels of corneal VEGF in all groups after alkali burn reached peak at 7～14d and decreased significantly at 28d, and the expression levels of VEGF in group A and group B at all time points after alkali burn were significantly lower than those in group C(P&#x003C;0.05), and group A was significantly lower than that in group B at 7, 14 and 21d(P&#x003C;0.05).CONCLUSION: The transplantation of hUCMSCs after alkali burn cornea can reduce the formation of CNV and inhibit corneal revascularization after alkali burn. The corneal pathological lesions and vascularization are closely related to PMNs and VEGF.

Research advances on the role and mechanism of microRNA in hypertrophic scar / 中华烧伤杂志

Hypertrophic scar (HS) affects the function and beauty of patients, and brings a heavy psychological burden to patients. However, the specific pathogenesis mechanism of HS in molecular biology level is not yet clear, and this disease is still one of the clinical diseases difficult to prevent and cure. MicroRNA (miR) is a family of single-stranded endogenous noncoding RNAs that can regulate gene expression. The abnormal transcription of miR in hypertrophic scar fibroblasts can affect the transduction and expression of downstream signal pathway or protein, and the exploration of miR and its downstream signal pathway and protein helps deeply understand the occurrence and development mechanism of scar hyperplasia. This article summarized and analyzed how miR and multiple signal pathways involve in the formation and development of HS in recent years, and further outlined the interaction between miR and target genes in HS.

Optimization of parameters for stir-frying of Kansui Radix with vinegar based on conversion of toxic components / 中国中药杂志

This study aims to optimize the parameters for stir-frying of Kansui Radix with vinegar based on the conversion of representative toxic diterpenes, which is expected to serve as a reference for the standardized production of Kansui Radix stir-fried with vinegar. To be specific, the toxic components [3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol(3-O-EZ), kansuiphorin C(KPC)] in Kansui Radix and the products(ingenol, 20-deoxyingenol) after the stir-frying with vinegar were selected. The toxicity to intestine and water-draining activity were evaluated with NCM460(normal human colon mucosal epithelial cell line) and HT-29(a human colorectal adenocarcinoma cell line). An HPLC method was then developed to assess the conversion of toxic components. On this basis, temperature, time, and amount of vinegar for the processing of Kansui Radix were optimized with the Box-Behnken design and the content of ingenol and 20-deoxyingenol as evaluation index. The results showed that after the stir-frying of Kansui Radix with vinegar, 3-O-EZ and KPC were first converted to monoester 3-O-(2'E,4'Z-decadienoyl)ingenol(3-EZ) and 5-O-benzoyl-20-deoxyingenol(5-O-Ben) and finally to almost non-toxic ingenol and 20-deoxyingenol, respectively. Meanwhile, the water-draining activity was retained. Six compounds had a good linear relationship with the peak area in the corresponding concentration ranges(R~2≥0.999 8), and the average recovery fell in the range of 98.20%-102.3%(RSD≤2.4%). The content of representative diterpenes and intermediate products was 14.78%-24.67% lower in the Kansui Radix stir-fried with vinegar than in the Kansui Radix, while the content of the conversed products was 14.37%-71.37% higher. Among the process parameters, temperature had significant influence on the total content of products, followed by time. The optimal parameters were 210 ℃, 15 min, and 30% vinegar. The relative error between the experimental results and the predicted values was 1.68%, indicating that the process was stable and reproducible. The strategy of screening optimal parameters for stir-frying of Kansui Radix with vinegar based on the transformation of toxic components can help improve the production stability, reduce the toxicity, and ensure the efficacy of Kansui Radix stir-fried with vinegar, which can serve as a reference for the process optimization of similar toxic Chinese medicinals.

Construction of cell factories for production of valencene in Saccharomyces cerevisiae / 药学学报

Valencene, a kind of sesquiterpenoid with a citrus flavor, is mainly found in Valencia orange and is commonly used in cosmetics and food additives, as well as industrial synthetic nootkatone. In this study, synthetic biology was used to create a Saccharomyces cerevisiae cell factory to produce valencene. Fistly, valencene synthase gene (CnVS) from Callitropsis nootkatensis was inserted into the chromosome of the chassis strain YTT-T5. The resulting strain VAL-01 could produce 1.1 mg·L-1 valencene. Protein fusion technique was used, different valencene synthases were compared and the copy number of key genes was adjusted, yielding valencene to 436.4 mg·L-1. Then, knocking-out the transcription factor ROX1 resulted in valencene improvement by 17.4%. Moreover, the induction system of galactose was regulated, transcription factor PDR3 and INO2 were overexpressed. The engineered strain VAL-10 could produce 2 798.6 mg·L-1 valencene by high cell density fermentation method (nearly 2 500 times higher than VAL-01). This study provides a basis for green production of valencene.

Role of blood markers in predicting the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation for treatment of periprosthetic joint infection / 中华外科杂志

Objective: To investigate the value of inflammation,coagulation and nutrition markers in predicting the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation for treatment of periprosthetic joint infection(PJI). Methods: A retrospective study was conducted on 70 patients who undertook prosthesis removal and antibiotic-loaded bone cement spacer implantation due to PJI from June 2016 to October 2020 in the Department of Orthopedics,Henan Provincial People's Hospital. There were 28 males and 42 females,aged (65.5±11.9) years (range: 37 to 88 years). Patients were divided into two groups as the successful group and the failed group depended on whether reinfection occurred after prosthesis removal and antibiotic-loaded bone cement spacer implantation at the last follow up. Patient demographics,laboratory values (C-reactive protein (CRP),erythrocyte sedimentation rate (ESR),ESR and CRP ratio (ESR/CRP),white blood cell count(WBC),platelet count(PLT),hemoglobin(HB),total lymphocyte count(TLC),albumin、fibrinogen(FIB),CRP and albumin ratio (CAR),prognostic nutritional index(PNI)),and reinfection rates were assessed. Comparison between groups was conducted by the independent sample t test or χ2 test. Receiver operating characteristic (ROC) curve was plotted,and the area under the curve (AUC),optimal diagnostic threshold,sensitivity,and specificity were analyzed to predict the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation. Results: All patients were followed up for at least two years,and the follow-up time was (38.4±15.2) months (range: 24 to 66 months). Fifteen patients suffered failure after prosthesis removal and antibiotic-loaded bone cement spacer implantation,while the other 55 patients succeeded. The overall failure rate of prosthesis removal and antibiotic-loaded bone cement spacer implantation in PJI treatment was 21.4%. Level of preoperative CRP(35.9±16.2)mg/L,PLT(280.0±104.0)×109/L and CAR 1.3±0.8 in successful group were lower than CRP (71.7±47.3)mg/L,PLT (364.7±119.3)×109/L and CAR 2.5±2.0 in failed group (all P<0.05).Whereas,level of preoperative ESR/CRP (3.3±3.1), Albumin (35.3±5.2)g/L and PNI 43.6±6.2 in successful group were higher than ESR/CRP (1.6±1.4),Albumin(31.3±4.8)g/L and PNI (39.2±15.1) in failed group (all P<0.05). AUC of ROC curve,optimal threshold value,sensitivity and specificity of CRP,ESR/CRP, PLT, Albumin,CAR and PNI for the predicting failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation were 0.776(95%CI:0.660 to 0.867),35.4 mg/L,86.7%,67.3%;0.725(95%CI:0.605 to 0.825),1.0,60.0%,78.2%;0.713(95%CI:0.593 to 0.815),253,93.3%,47.3%;0.721(95%CI:0.601 to 0.822),35.7,93.3%,49.1%;0.772(95%CI:0.656 to 0.863),1.1,86.7%,67.3%;0.706(95%CI:0.585 to 0.809),45.7,100%,41.8% respectively. Conclusion: In patients with PJI,CRP>35.4,ESR/CRP≤1.0 and CAR>1.1 could predict the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation.

Progress on genome-wide association studies on mosaic chromosomal alterations / 中华流行病学杂志

Mosaic chromosomal alteration (mCA) is referred to as large-scale somatic mutations on chromosomes, which results in diverse karyotypes in body. The mCA is regarded as one of the phenotypes of aging. Studies have revealed its associations with many chronic diseases such as hematopoietic cancers and cardiovascular diseases, but its genetic basis (e.g. genetic susceptibility variants) is still under-investigated. This paper reviews GWAS studies for mCA on autosomal chromosomes and sex chromosomes [mosaic loss of the Y chromosome (mLOY) and mosaic loss of the X chromosome (mLOX)] based on large population, respectively. Most of the genetic susceptibility loci found in studies for autosomal mCA were associated with copy-neutral loss of heterozygosity. The study of sex chromosome mCA focused on mosaic loss mutations. The number of genetic susceptibility loci for mLOY was high (up to 156), but it was relatively less for mLOX.

Epidemiological distribution characteristics of peripheral blood mosaic chromosomal alteration in adults from 10 regions of China / 中华流行病学杂志

Objective: To describe the epidemiological distribution characteristics of peripheral blood mosaic chromosomal alteration (mCA) in community adults aged 30-79 years in 10 regions of China. Methods: A total of 100 297 participants with complete baseline information (demographic characteristics, lifestyle, physical examination, etc.) and genotyping data of blood-derived DNA in ten regions of the China Kadoorie Biobank study were included. The mCAs were detected with the Mosaic Chromosomal Alterations pipeline, and logistic regression models were used to compare the differences in the detection rate of mCAs in different regions and populations. Results: A total of 5 810 mCA carriers were detected, with the detection rate of 5.8%. The standardized detection rate was 5.1%. The baseline detection rate of mCA increased with age, which were 3.4%, 5.0%, and 9.4% in those aged 30-, 51-, and >60 years, respectively (trend test P<0.001). A more significant proportion of mCAs were found in men (8.0%) than women (4.0%), as well as in urban areas (6.4%) than in rural areas (5.3%), the difference was significant (P<0.001). After adjusting for age and gender, the detection rate of mCA was higher in current smokers or people quitting smoking due to illness and people with low physical activity level, and the mCA detection rate was lower in obesy people (5.3%) than that in people with normal body weight (5.9%) (P=0.006). Conclusions: The detection rate of mCAs varied with region and population in community adults aged 30-79 years in 10 regions of China. The study results might contribute to the molecular identification of aging populations and guide precision prevention of age-related diseases such as cancers.

A design and evaluation of wearable p300 brain-computer interface system based on Hololens2 / 生物医学工程学杂志

Patients with amyotrophic lateral sclerosis ( ALS ) often have difficulty in expressing their intentions through language and behavior, which prevents them from communicating properly with the outside world and seriously affects their quality of life. The brain-computer interface (BCI) has received much attention as an aid for ALS patients to communicate with the outside world, but the heavy device causes inconvenience to patients in the application process. To improve the portability of the BCI system, this paper proposed a wearable P300-speller brain-computer interface system based on the augmented reality (MR-BCI). This system used Hololens2 augmented reality device to present the paradigm, an OpenBCI device to capture EEG signals, and Jetson Nano embedded computer to process the data. Meanwhile, to optimize the system's performance for character recognition, this paper proposed a convolutional neural network classification method with low computational complexity applied to the embedded system for real-time classification. The results showed that compared with the P300-speller brain-computer interface system based on the computer screen (CS-BCI), MR-BCI induced an increase in the amplitude of the P300 component, an increase in accuracy of 1.7% and 1.4% in offline and online experiments, respectively, and an increase in the information transfer rate of 0.7 bit/min. The MR-BCI proposed in this paper achieves a wearable BCI system based on guaranteed system performance. It has a positive effect on the realization of the clinical application of BCI.

Acacetin protects rats from cerebral ischemia-reperfusion injury by regulating TLR4/NLRP3 signaling pathway / 中国中药杂志

This study aims to investigate the mechanism of acacetin in protecting rats from cerebral ischemia-reperfusion injury via the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. Wistar rats were randomized into sham, model, low-and high-dose acacetin, and nimodipine groups, with 10 rats in each group. The rat model of middle cerebral artery occlusion(MCAO) was established with the improved suture method in other groups except the sham group. The neurological deficit score and cerebral infarction volume of each group were evaluated 24 h after modeling. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interleukin-1β(IL-1β), IL-6, tumor necrosis factor-α(TNF-α), malondialdehyde(MDA), supe-roxide dismutase(SOD), and glutathione(GSH). Western blot was employed to determine the expression levels of B-cell lymphonoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and TLR4/NLRP3 signaling pathway-related proteins(TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1β, and cleaved IL-1β) in the rat brain tissue. Hematoxylin-eosin(HE) staining was employed to reveal the histopathological changes in the ischemic area. Compared with the sham group, the modeling of MCAO increased the neurological deficit score and cerebral infarction volume, elevated the IL-1β, IL-6, TNF-α, and MDA levels and lowered the SOD and GSH levels in the brain tissue(P<0.05). Compared with the MCAO model group, low-and high-dose acacetin and nimodipine decreased the neurological deficit score and cerebral infarction volume, lowered the IL-1β, IL-6, TNF-α, and MDA levels and elevated the SOD and GSH levels in the brain tissue(P<0.05). Compared with the sham group, the model group showed up-regulated protein levels of Bax, TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1β, and cleaved IL-1β and down-regulated protein level of Bcl-2 in the brain tissue(P<0.05). Compared with the MCAO model group, the acacetin and nimodipine groups showed down-regulated protein levels of Bax, TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1β, and cleaved IL-1β and up-regulated protein level of Bcl-2 in the brain tissue(P<0.05). In conclusion, acacetin regulates the TLR4/NLRP3 signaling pathway to inhibit neuroinflammatory response and oxidative stress, thus exerting the protective effect on cerebral ischemia-reperfusion injury in rats.

A multi-center observation of the therapeutic efficacy of Bencycloquidium bromide in the treatment of seasonal allergic rhinitis with predominant symptoms of rhinorrhea / 临床耳鼻咽喉头颈外科杂志

Objective:To observe the efficacy and safety of the M receptor antagonist Bencycloquidium bromide nasal spray in treatment of seasonal allergic rhinitis with runny nose as the main symptom. Methods:From August 2021 to September 2021, 134 patients with seasonal allergic rhinitis were enrolled in the otolaryngology Outpatient Department of Peking University Third Hospital, First Affiliated Hospital of Harbin Medical University and China-Japanese Friendship Hospital of Jilin University, including 71 males and 63 females, with a median age of 38 years. TNSS score and visual analogue scale（VAS） of total nasal symptoms were observed during 2 weeks of treatment with Bencycloquidium bromide nasal spray. Results:TNSS score decreased from （8.89±3.31） on day 0 to （3.71±2.51） on day 14（P<0.001）, VAS score of nasal symptoms decreased from （24.86±7.40） on day 0 to （6.84±5.94） on day 14（P<0.001）, VAS score of rhinorrhoea decreased from （6.88±2.06） on day 0 to （1.91±1.81） on day 14（P<0.001）. Rhinoconjunctivitis quality of life questionnaire（RQLQ） score decreased from （94.63±33.35） on day 0 to （44.95±32.28） on day 14（P<0.001）. The incidence of adverse reaction was low and no serious adverse events occurred during the whole experiment. Conclusion:Bencycloquidium bromide nasal spray has significant efficacy and good safety in the treatment of seasonal allergic rhinitis.

Exploring the material basis of genipin-induced hepatotoxicity in vitro / 药学学报

The current study explored the hepatotoxicity among closed-ring genipin, open-ring tautomer of genipin and gardenia blue that generated from genipin and amino acid reaction using HepaRG cells to identify the material basis of genipin-induced hepatotoxicity in vitro. The effects of temperature, pH value and different kinds of amino acids on the chemical structure tautomerism between closed-ring and open-ring tautomer of genipin and the production of gardenia blue were investigated firstly, which aimed to explicit the conditions that could distinguish the closed-ring genipin and its open-ring tautomer, and the conditions generating gardenia blue, which were applied to prepare different kinds of gardenia blue; the CCK-8 kit was employed to analyze the hepatotoxicity of closed-ring genipin, open-ring tautomer of genipin and gardenia blue. From the results, it was found that, the structure transformation from close-ring to open-ring of genipin could be inhibited under the condition with acid environment; being essential groups to generate gardenia blue, the primary amino group and the open-ring tautomer of genipin reacting to generate the dihydropyridine ring was probably the key structure of gardenia blue; the structure characteristics existed apparent distinction at the reactive temperature of 37 ℃ and 80 ℃; compared to the culture condition with pH = 7.4, the concentration of genipin with close-ring in culture medium was significantly increased at pH = 5, but the cell viability did not decreased; the cell toxicity of gardenia blue was apparently lower than open-ring tautomer of genipin, and even some kinds of gardenia blue showed growth promoting effect on HepaRG cells. Here, it was suggested potentially that open-ring tautomer of genipin be the important material basis to induce hepatotoxicity, which could provide a cue and lay a foundation for the elucidation of the underlying mechanism of genipin-induced hepatotoxicity.

Relationship between BNIP3L and mitochondrial dysfunction in hippocampus of mice with sepsis-associated encephalopathy / 中华麻醉学杂志

Objective:To evaluate the relationship between B-cell lymphoma/adenovirus E1B19 kDa-interacting protein 3-like protein (BNIP3L)/adenovirus E1B-interacting protein and mitochondrial dysfunction in the hippocampus of mice with sepsis-associated encephalopathy (SAE).Methods:One hundred and eighty C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=45 each) using a random number table method: control group (C group), sham operation group (Sham group), SAE group, and SAE+ BNIP3L agonist carfilzomib group (SC group). The sepsis model was developed by cecal ligation and puncture (CLP) in anesthetized animals. In SC group, carfilzomib 2 mg/kg was intraperitoneally injected at 2 h after CLP. Twenty mice in each group were selected, and the survival at 7 days after operation was recorded. Eight surviving mice in each group were selected at 1 week after CLP for Morris water maze test. The remaining mice were sacrificed at 24 h after surgery, and the hippocampal tissues were harvested for determination of the expression of BNIP3L (by immunofluorescence) and BNIP3L in mitochondrial protein (by Western blot) and for microscopic examination of the morphological structure of mitochondria. The mitochondrial ATP content was measured by fluorescein-fluorescence enzyme luminescence method, and the mitochondrial membrane potential (MMP) was measured by fluorescence spectrophotometry. Results:Compared with C and Sham groups, the survival rate was significantly decreased, the escape latency was prolonged, the time of staying at the original platform quadrant was shortened, and the number of crossing the original platform region was decreased, the expression of BNIP3L in the hippocampal mitochondria was down-regulated, the MMP and content of mitochondrial ATP were decreased ( P<0.05), the intensity of fluorescence of BNIP3L in the hippocampus was decreased, and the damage to mitochondrial ultrastructure was marked in SAE group. Compared with SAE group, the survival rate was significantly increased, the escape latency was shortened, the time of staying at the original platform quadrant was prolonged, and the number of crossing the original platform region was increased, the expression of BNIP3L in the hippocampal mitochondria was up-regulated, the MMP and content of mitochondrial ATP were increased ( P<0.05), the intensity of fluorescence of BNIP3L in the hippocampus was decreased, and the damage to mitochondrial ultrastructure was attenuated in SC group. Conclusions:BNIP3L-mediated mitochondrial dysfunction may be involved in the mechanism of SAE developed in mice.

Effect of high concentration hydrogen on myocardial injury and expression of Mst1 in septic mice / 中华麻醉学杂志

Objective:To evaluate the effect of high concentration hydrogen on myocardial injury and expression of mammalian STE20-like protein kinases 1 (Mst1) in septic mice.Methods:One hundred and five clean-grade healthy male C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=35 each) using a random number table method: sham operation group (group Sham), sepsis group (group SEP), and sepsis+ high concentration hydrogen group (group SEP+ HCH). The model of sepsis-induced myocardial injury was developed by cecal ligation and perforation in anesthetized mice. In SEP+ HCH group, high concentration hydrogen (66.7%) was inhaled for 1 h starting from 1 and 6 h after the successful preparation of the model. Twenty mice were taken from each group to observe the survival rate at day 7 after operation. Blood samples from the medial canthus were collected after deep anesthesia at 24 h after surgery for determination of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) concentrations (by enzyme-linked immunosorbent assay). Then the animals were sacrificed, and the heart tissues were taken for examination of the pathological results (with a light microscope) which were scored and for determination of apoptosis in myocardial cells (by TUNEL) and expression of Mst1, dynamic-related protein 1 (Drp1) and mitofusin 2 (Mfn2) in myocardium (by Western blot). Results:Compared with group Sham, the survival rate at 7 days after operation, pathological score, apoptosis index and concentrations of TNF-α and IL-6 were significantly increased, Mst1 and Drp1 expression was up-regulated, and Mfn2 expression was down-regulated in group SEP ( P<0.05). Compared with group SEP, the survival rate at 7 days after operation, pathological score, apoptosis index and concentrations of TNF-α and IL-6 were significantly decreased, Mst1 and Drp1 expression was down-regulated, and Mfn2 expression was up-regulated in group SEP+ HCH ( P<0.05). Conclusions:Inhalation of high-concentration hydrogen can attenuate the myocardial injury in septic mice, and the mechanism may be related to down-regulation of Mst1 expression, improvement in mitochondrial dynamics, and inhibition of apoptosis in myocardial cells.

Comparison of ocular microbiomes between patients with and without dry eye / 中华实验眼科杂志

Objective:To explore the difference in ocular surface microbiota between patients with and without dry eye.Methods:Forty-two patients (42 eyes) diagnosed with dry eye were enrolled as dry eye group in the First Affiliated Hospital of Xi'an Jiaotong University from June to November 2020, and 37 controls without dry eye (37 eyes) were enrolled as control group in the same period.One eye was selected as the study eye, and the right eye was included when both eyes met the inclusion criteria.Swab samples from the conjunctival sac were obtained and sequenced.Sequencing of the V3-V4 region of the bacterial 16S rRNA gene was performed with Miseq PE301+ 8+ 301 platform.Operational taxonomic species (OTUs) clustering of microflora, comparison of alpha and beta diversity analysis of microflora between the two groups, annotation analysis of species and analysis of microbial markers were performed.The study protocol was approved by the Ethics Committee of The First Affiliated Hospital of Xi'an Jiaotong University (No.XJTU1AFCRC2018SJ-014). Written informed consent was obtained from each subject before any medical examination.Results:A total of 18 586 OTUs were obtained, and 3 674 OTUs were shared between the two groups.Alpha diversity analysis showed that there was no significant difference in observed species index, Chao index, Ace index, Shannon index and Simpson index between the two groups (all at P>0.05), suggesting there was no difference in microbiota richness between them.The PCoA analysis showed that the microbial compositions of the two groups were significantly different ( R2=0.039, F=3.100, P=0.022). The dominant flora of the two groups was similar, with Proteobacteria, Actinobacteria, Firmicutes, Bacteroidetes and Cyanobacteria as the top 5 abundant bacterial phyla, with Pelomonas, Corynebacterium, Propionibacterium, Pseudomonas and Herbaspirillum as the top 5 bacterial genera.LEfSe analysis identified Tissierellaceae, Enhydrobater and Finegoldia as dominant bacterial genera in dry eye group, and Caulobacter and Curvibacter in control group. Conclusions:The composition of ocular surface microbiomes is different between dry eye patients and controls.