1.Data mining and analysis for ADE signals of three third-generation tetracycline antibiotics
Biyi LIANG ; Huixia YANG ; Xiaomei HUANG ; Jianxiong REN
China Pharmacy 2024;35(9):1123-1128
OBJECTIVE To excavate the adverse drug event (ADE) signals of three third-generation tetracycline antibiotics (tigecycline, omadacycline, eravacycline) based on FDA adverse event reporting system (FAERS), and to provide reference for the safe use of them. METHODS The ADE reports of tigecycline, omadacycline and eravacycline from the first quarter of 2005 to the second quarter of 2023 were retrieved from FAERS database. The ADE signals of 3 kinds of drugs were mined by the method of reporting odds ratio method and the proportional reporting ratio method. RESULTS Totally 2 538 ADE reports with tigecycline, omadacycline and eravacycline as the primary suspected drugs were obtained, including 2 135 tigecycline ADE reports, 349 omadacycline ADE reports and 54 eravacycline ADE reports. A total of 131 ADE positive signals of tigecycline were mined, involving 19 system organ classes (SOCs), mainly concentrated in investigations, hepatobiliary system, blood and lymphatic system, and gastrointestinal system, etc; the preferred terminologies (PT) with intense signal were hypofibrinogenaemia and blood fibrinogen decreased. Fourteen ADE signals were not mentioned in the drug instruction, such as renal failure, acute kidney injury and hemorrhage. Totally 24 ADE positive signals of omadacycline were mined, involving 6 SOCs, mainly concentrated in the gastrointestinal system and various examinations; the PTs with intense signals were tooth discoloration, jet-like vomiting and loose feces, etc. ADE signals were not mentioned in the drug instructions, included lip swelling, gastroesophageal reflux disease, eosinophilia, skin discoloration, feces softening, and night sweats. Five ADE positive signals of eravacycline were mined, involving 4 SOCs, mainly concentrated in various examinations, gastrointestinal system, etc. The most intense ADE signals were blood fibrinogen decreased and hypofibrinogenaemia. CONCLUSIONS ADE of the gastrointestinal system are mostly identified in the three third-generation tetracycline antibiotics, especially pancreatitis caused by tigecycline and gastroesophageal reflux disease caused by oral administration of omadacycline. The liver function, renal function (for tigecycline) and coagulation function (for tigecycline, eravacycline) should be monitored biyiliang@hotmail.com regularly during medication, so as to prevent the occurrence of serious ADE.
2.Effect of autophagy inhibition on prognoses of rats with severe traumatic brain injury
Zhaomeng WEN ; Yuwei SHI ; Wenhu LIU ; Shaobo MA ; Jian ZHANG ; Jianxiong LIU ; Jin LIANG
Chinese Journal of Neuromedicine 2024;23(5):433-442
Objective:To investigate the activation of ubiquitin proteasome system (UPS) and autophagy in brain tissues of rats after severe traumatic brain injury (sTBI) and the role of autophagy in secondary traumatic brain injury.Methods:(1) Twenty-five SD rats were randomly divided into sham-operated group, group of 3 h after sTBI, group of 1 d after sTBI, group of 3 d after sTBI and group of 7 d after sTBI ( n=5). Only bone window was opened in sham-operated group, and controlled cortical impact (CCI)-induced sTBI models were established in the other 4 groups. Western blotting was used to detect the expressions of free ubiquitin, ubiquitinated protein, vacuolar protein sorting 34 (VPS34), P62, microtubule-associated protein-light chain 3-II, and Mature-cathepsin D (CTSD). (2) One hundred SD rats were randomly divided into normal control group, sTBI group, lactacystin group and SAR405 group ( n=25). Ten μL lactacystin or SAR405 were stereotactically injected into the lateral ventricle of lactacystin group and SAR405 group, respectively; 30 min after that, CCI-induced sTBI models were established in the sTBI group, lactacystin group and SAR405 group. Three d after modeling, the expressions of ubiquitinated protein, LC3-II, P62, and Caspase-3 were detected by Western blotting; percentage of brain water content was determined by dry/wet weight ratio; neurological functions were assessed by modified neurological deficit scale (mNSS); degrees of brain tissue damage were detected by HE staining; and cerebral blood perfusion was detected by laser scattering hemodynamic imaging system. Results:(1) Compared with sham-operated group, group of 3 h after sTBI, group of 1 d after sTBI, group of 3 d after sTBI and group of 7 d after sTBI had significantly decreased free ubiquitin, and group of 1 d after sTBI, group of 3 d after sTBI and group of 7 d after sTBI had significantly increased ubiquitinated protein in the brain tissues surrounding the injury lesions ( P<0.05). Compared with sham-operated group, group of 3 d after sTBI and group of 7 d after sTBI had statistically increased VPS34 and Mature-CTSD and significantly decreased P62 and group of 1 d after sTBI, group of 3 d after sTBI and group of 7 d after sTBI had significantly increased LC3-II in the brain tissues surrounding the injury lesions ( P<0.05). (2) The ubiquitinated protein relative expressions in the brain tissues surrounding the injury lesions of normal control group, sTBI group, lactacystin group and SAR405 group were 4.78±2.63, 10.62±0.73, 13.45±1.22 and 8.50±0.83, respectively, with significant differences ( P<0.05). Compared with the normal control group, the sTBI group, lactacystin group and SAR405 group had significantly higher LC3-II, ubiquitinated protein and cleaved caspase-3/pro-caspase-3, and significantly lower P62 in the brain tissues surrounding the injury lesions ( P<0.05); compared with the the sTBI group, the lactacystin group had significantly higher LC3-II, ubiquitinated protein, and cleaved caspase-3/pro-caspase-3, and significantly lower P62 in the brain tissues surrounding the injury lesions ( P<0.05); compared with the the sTBI group, the SAR405 group had significantly lower LC3-II, ubiquitinated protein and cleaved caspase-3/pro-caspase-3, and significantly higher P62 in the brain tissues surrounding the injury lesions ( P<0.05). Compared with the normal control group([67.60±2.51]%、[0±0] scores、[333.41±46.86] PU), the sTBI group, lactacystin group and SAR405 group had statistically higher percentage of brain water content and mNSS scores ([80.2±1.30]%, [87.0±1.58]% and [71.60±1.81]%; 13.8±1.10, 16.4±0.55 and 10.40±1.14) and signficantly lower cerebral blood perfusion volume ([53.98±5.99] PU, [21.71±2.62] PU and [87.97±6.75] PU, P<0.05); compared with the sTBI group, the lactacystin group had significantly higher brain water content and mNSS scores, and significantly lower cerebral blood perfusion volume ( P<0.05); compared with the sTBI group, the SAR405 group had significantly lower brain water content and mNSS scores, and significantly higher cerebral blood perfusion volume ( P<0.05). HE staining showed that the cortical tissues were most severely damaged in the lactacystin group, followed by the sTBI group; the least damage was noted in the SAR405 group, and no significant damage in the normal control group was noted. Conclusion:After sTBI, UPS activation is earlier than autophagy; autophagy inhibition helps to alleviate UPS dysfunction, reduce Caspase-3-induced apoptosis, and is beneficial to the recovery of neurological function.
3.Heterozygous CARD9 mutation favors the development of allergic bronchopulmonary aspergillosis.
Xia XU ; Haiwen LU ; Jianxiong LI ; Jielin DUAN ; Zhongwei WANG ; Jiawei YANG ; Shuyi GU ; Rongguang LUO ; Shuo LIANG ; Wei TANG ; Fengying ZHANG ; Jingqing HANG ; Juan GE ; Xin LIN ; Jieming QU ; Xinming JIA ; Jinfu XU
Chinese Medical Journal 2023;136(16):1949-1958
BACKGROUND:
Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA.
METHODS:
A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease.
RESULTS:
The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production.
CONCLUSION
Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.
Humans
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Aspergillosis, Allergic Bronchopulmonary/complications*
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Aspergillus fumigatus/genetics*
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Asthma/genetics*
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Aspergillus
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Mutation/genetics*
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CARD Signaling Adaptor Proteins/genetics*
4.Sexual and reproductive health knowledge and practice among students in six senior high schools in three regions in East China
Ying-hong LU ; Li-ping ZHU ; Biao ZHANG ; Hong-fang MAO ; Peng-fei LIANG ; Bing-ying LI ; Li DU ; Biao XU
Shanghai Journal of Preventive Medicine 2021;33(9):838-844
Objective:To know the status of knowledge, attitude and behavior related to sexual and reproductive health in high school students in three regions of East China, and to provide a reference for adolescent reproductive health education
5.A study on the identification of threshold for early warning on adverse weather events based on the association of apparent temperature and years of life lost
Siqi CHEN ; Min YU ; Maigeng ZHOU ; Chunliang ZHOU ; Yize XIAO ; Biao HUANG ; Yanjun XU ; Liang ZHAO ; Jianxiong HU ; Xiaojun XU ; Tao LIU ; Jianpeng XIAO ; Weilin ZENG ; Lingchuan GUO ; Xing LI ; Wenjun MA
Chinese Journal of Epidemiology 2021;42(8):1445-1452
Objective:To identify the threshold of a health warning system based on the association of apparent temperature and years of life lost (YLL).Methods:Daily mortality records and meteorological data were collected from 364 Chinese counties for 2006-2017. Distributed lag nonlinear model and multivariate Meta-analyses were applied to estimate the association between the apparent temperature and YLL rate. A regression tree model was employed to estimate the warning thresholds of the apparent temperature. Stratified analyses were further conducted by age and cause of death.Results:The daily YLL rate was 23.6/10 5. The mean daily apparent temperature was 15.7 ℃. U-shaped nonlinear associations were observed between apparent temperature and YLL rate. The actual temperature-caused YLL rate for the elderly was higher than the young population. The daily excess deaths rate increased with the higher effect levels. Conclusions:Regression tree model was employed to define the warning threshold for meteorological health risk. The present study provides theoretical support for the weather-related health warning system.
6.Prevalence and risk factors of exit-site infection in elderly peritoneal dialysis patients
Jianxiong LIN ; Bining LIANG ; Shuchao LU ; Shan LYU ; Xiaoli YU ; Haiping MAO ; Xueqing YU ; Xiao YANG
Chinese Journal of Nephrology 2020;36(6):417-423
Objective:To explore the prevalence and risk factors of exit-site infection (ESI) in elderly peritoneal dialysis (PD) patients.Methods:The status of exit-site was evaluated in elderly PD patients (≥60 years) who had catheter insertion in our center between January 1, 2009 and December 31, 2013, with follow-up for 1 year or withdrawing from peritoneal dialysis in this period. The patients were divided into ESI and non-ESI group. The data was collected including demographics, clinical features, and nursing care methods of the exit-site.Results:A total of 247 patients were recruited in this study, aged (68.6±6.2) years, among whom there were 132 male (53.4%) and 119 diabetes (48.2%). Median follow-up time was 12.0 months. Thirty-two patients had 34 episodes of ESI with a rate of 82.5 patient-months per episode (0.15 episodes per year). Coagulase-negative Staphylococcus was the main pathogen, accounting for 35.3% of the ESI. No bacterial growth was found in 8.8%. The exit-site nursing care status included that poor compliance of exit-site care 23.5%, poor catheter immobilization 62.3%, history of catheter-pulling injury 9.7%, mechanical stress on exit-site 5.3%, improper frequency of nursing care 29.6%, mupirocin usage 13.8%, patients taking exit-site care 26.7%, exit-site caregiver instability 16.6%. There were no differences in demographic (such as age, gender, primary disease, etc) and laboratory data (hemoglobin, serum albumin, blood potassium, etc) between the ESI and non-ESI groups. Poor compliance with exit-site care ( HR=2.352, 95% CI 1.008-5.488, P=0.048), poor catheter immobilization ( HR=3.074, 95% CI 1.046-9.035, P=0.041) and exit-site caregiver instability ( HR=2.423, 95% CI 1.004-5.845, P=0.049) were significantly correlated with increased risk of ESI. Conclusions:The prevalence of ESI in elderly PD patients was 0.15 episodes per year. Educating PD patients to improve the compliance with exit-site care, maintain catheter immobilization and do exit-site care by a stable and trained caregiver may reduce ESI events in elderly PD patients.
7.Treatment of delayed deep infection after spinal fixation
Dong YIN ; Xiaoqing ZHENG ; Honglin GU ; Yongxiong HUANG ; Jianxiong ZHUANG ; Guoyan LIANG ; Shuaihao HUANG ; Changxiang LIANG ; Yunbing CHANG
Chinese Journal of Orthopaedics 2017;37(18):1150-1155
Objective To explore the efficacy of early aggressive debridement with implant retention, primary wound clo-sure, closed suction drain without irrigation and antibiotic therapy for the treatment of delayed deep infection after spinal fixation. Methods 4057 patients were underwent dorsal spinal fixation from January 2010 to June 2014. Among them, 42 cases of de-layed deep infection after operation were included in the study. There were 25 males and 17 females, with an average age of 68.6± 8.1 years (ranged from 53 to 83 years). The diagnosis of delayed deep infection was based on the time of onset, clinical symptoms and signs, imaging and laboratory findings. Surgical debridement was performed immediately after diagnosis of infection. In addi-tion, devitalized and necrotic tissue and biofilms which adhered to the surface of the implant were removed meticulously and thor-oughly. Primary wound closure was performed in each patient, and closed suction drains were maintained for about 7-10 d without irrigation. Routine sensitive antimicrobial drugs was applied for 3 months after operation. Results 42 cases were all followed up for 24 to 72 months with an average of 46 months. Among the 42 infected patients, 3 patients were underwent posterior cervical spine surgery and 39 patients were underwent posterior lumbar spine surgery. There were 13 cases of staphylococcus aureus infec-tion, 7 cases of escherichia coli infection, 3 cases of ESBL escherichia coli infection, 3 cases of enterobacter cloacae infection, 2 cases of MRSA, 2 cases of acinetobacter baumannii infection, 2 cases of klebsiella pneumoniae infection, 1 case in enterococcus faecium and pseudomonas aeruginosa and staphylococcus haemolyticus, respectively. There were still 7 patients with negative bacterial culture. 41 cases retained their implant, whereas 1 staphylococcus aureus infection patient had the implants removed be-cause of loosening during debridement. Nevertheless, primary wound healing was found in all patients, and stitches were removed 2 to 3 weeks after debridement. Infections were effectively controlled with no recurrence of infection during the follow-up. The av-erage erythrocyte sedimentation rate was (65.76±20.08) mm/h preoperative, (41.43±14.65) mm/h 1 month postoperative, (10.81±2.72) mm/h 6 months postoperative, and (8.10±5.46) mm/h 12 months postoperative, respectively, the differences were statistically significant. The average C reactive protein was (40.55±16.91) mg/L preoperative, (6.50±2.46) mg/L 1 month postoperative, (4.31± 1.26) mg/L 6 months postoperative, and (3.83±1.50) mg/L 12 months postoperative, respectively, the differences were statistically significant. The average procalcitonin was (0.47±0.28) ng/ml preoperative, (0.08±0.06) ng/ml 1 month postoperative, (0.06±0.03) ng/ml 6 months postoperative, and (0.05±0.00) ng/ml 12 months postoperative, respectively, and the differences were statistically significant. Conclusion A timely diagnosis, aggressive and meticulous debridement, high vacuum closed-suction drain, routine and adequate use of antibacterial agents are keys to successfully resolving infection and maintaining implant retention in the treat-ment of delayed deep infection after spinal fixation.
8.Synthesis of 6-benzyl-1-[ (benzyloxy) methyl ]-3-hydroxy-5-(hydroxymethyl) pyrimi-dine-2,4(1H,3H)-dione
Xiaowan TANG ; Liang ZHANG ; Jianxiong ZHAO ; Yu ZHANG ; Ying GUO ; Zhili ZHANG ; Chao TIAN ; Xiaowei WANG ; Junyi LIU
Journal of Peking University(Health Sciences) 2015;(5):838-841
Objective:To find the best synthesis method of 6-benzyl-1-[ ( benzyloxy ) methyl ]-3-hydro-xy-5-(hydroxymethyl)pyrimidine-2,4(1H,3H)-dione e for observing the change of its biological activity after N-3 hydroxylation .Methods:After trying some N-hydroxylation methods , the target compound was successfully synthesized via one-pot oxidizing process by sodium hydride ( NaH) and 3-chloroperbenzoic acid( m-CPBA);the anti-HIV reverse transcriptase ( RT) activity and integrase ( IN) activity of the tar-get compound was assayed via enzyme-linked immunesorbent assay ( ELISA) and phosphorylation of DNA package method .Results:The target compound could be obtained through the improved m-CPBA oxida-tive method by only one step , and the yield of the reaction could reach 60%-70%.And the structure of this compound was identified by 1 H NMR, 13 C NMR and MS;The activity result showed it added the an-ti-HIV IN activity after N-3 hydroxylation as well as retained the anti-HIV RT activity.Conclusion:The improved m-CPBA oxidative method is a convenient and efficient way to prepare the compound 6-benzyl-1-[(benzyloxy)methyl]-3-hydroxy-5-(hydroxymethyl)pyrimidine-2,4(1H,3H)-dione e which has both anti-HIV RT and IN activity .
9.Clinical features of ischemic stroke in patients with nasopharyngeal carcinoma
Yayuan LIU ; Zhijian LIANG ; Chao QIN ; Daobin CHENG ; Jianxiong WU ; Lixia YU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2015;50(5):411-414
Objective To investigate the clinical features of ischemic stroke in patients with nasopharyngeal carcinoma.Methods The clinical data of the nasopharyngeal carcinoma patients with ischemic stroke treated at the First Affiliated Hospital of Guangxi Medical University between January 2006 and December 2013 were collected.Results Among 3 822 patients with nasopharyngeal carcinoma l0 patients suffered from acute ischemic stroke.The 10 patients were males and their age ranged from 39 to 70 years old,with an average age of 51 years.All of the patients were found with squamous cell carcinoma,with metastasis in 7 of them.Among the 10 patients,only 3 patients had with traditional risk factors for ischemic stroke,but no traditional risk factor was found in other 7 patients;2 patients showed single lesion in brain and 8 patients with two or more lesions due to the blockage of multiple cerebral arteries;7 patients showed an elevated plasma D-dimer level.Conclusion It is suggested that the acute ischemic stroke occurring in the patients with nasopharyngeal carcinoma commonly lacks traditional risk factors,with elevated plasma D-dimer levels and multiple lesions due to involvement of several cerebral arteries.
10.Immune modulatory function of abundant immune-related microRNAs in microvesicles from bovine colostrum.
Qi SUN ; Xi CHEN ; Jianxiong YU ; Ke ZEN ; Chen-Yu ZHANG ; Liang LI
Protein & Cell 2013;4(3):197-210
Colostrum provides essential nutrients and immunologically active factors that are beneficial to newborns. Our previous work demonstrated that milk contains large amounts of miRNA that is largely stored in milk-derived microvesicles (MVs). In the present study, we found that the MVs from colostrum contain significantly higher levels of several immune-related miRNAs. We hypothesized that the colostrum MVs may transfer the immune-related miRNAs into cells, which contribute to its immune modulatory feature. We isolated colostrum MVs by ultracentrifugation and demonstrated several immune modulation features associated with miRNAs. We also provide evidence that the physical structure of milk-derived MVs is essential for transfer miRNAs and following immune modulation effect. Moreover, we found that colostrum powder-derived MVs also contains higher levels of immune-related miRNAs that display similar immune modulation effects. Taken together, these results show that MV-containing immunerelated miRNAs may be a novel mechanism by which colostrum modulates body immune response.
Animals
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Cattle
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Cell Movement
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Cell Proliferation
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Colostrum
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metabolism
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Cytokines
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metabolism
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Female
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Liposomes
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chemistry
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isolation & purification
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metabolism
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Macrophages
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immunology
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metabolism
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Mice
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MicroRNAs
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immunology
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metabolism
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Milk
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immunology
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metabolism
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Phagocytosis
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Pregnancy
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Ultracentrifugation

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