Objective To understand the incidence and characteristics of adverse drug reactions(ADRs)of carbapenems,explore the relevant risk signals,and provide a reference for clinically safe drug use.Methods All spontaneous reports of carbapenem drug-related ADRs from January 2008 to October 2022 in the Adverse Drug Reaction Monitoring Center,PLA General Hospital's ADR database were retrieved,and information such as patients'general conditions,involved systems and organs damage,and the names of ADRs involved were retrospectively analysed.Using the reporting odd ratio method,the proportional reporting ratio method,the Medicines and Healthcare Products Regulatory Agency method,and information component method to obtain risk signals of carbapenem antimicrobial drug-related ADR.Results A total of 2 642 ADR reports of carbapenems were reported,of which 410 serious ADR reports(15.52％)were serious ADR reports,five cabapenem antimirobial drug species were mainly involved.In descending order of composition were imipenem cilastatin(51.28％),meropenem(32.13％),biapenem(8.10％),ertapenem(7.68％),and panipenem(0.79％).The male to female ratio of patients was 1.74:1,with the most age＞60 years(59.69％).A total of 14"drug-ADR name"combinations generated risk signals in all four data mining methods,with meropenem being the most signals,and imipenem cilastatin and ertapenem had a high number of reported ADR in nervous system.Conclusion The results of risk signal mining are basically consistent with the known carbapenem ADR information,during the use of carbapenem antimicrobial drugs in the clinic,it is recommended to monitor patients'liver and kidney functions as well as blood biochemical indexes,so as to strengthen the awareness of vigilance in the clinical use of carbapenem antimicrobial drugs,and timely recognize and deal with ADRs in a timely manner,and to avoid the occurrence of serious ADRs.

Objective:To explore the pregnancy outcome of intracytoplasmic sperm injection (ICSI)/rescure-ICSI (Re-ICSI) patients with gear-like transparent dense zona pellucida and small perivitelline oocytes.Methods:Totally 6 couples with abnormal zona pellucida came to the Reproductive Medicine Center of Shijiazhuang the Fourth Hospital from January 2015 to June 2020 were retrospectively case control analyzed. A total of 8 cycles had zona pellucida abnormalities, of which 5 couples, the proportion of M I oocytes was ≥50% (part oocytes M I arrest) in 6 cycles and 1 couple (2 cycles) was all oocytes M I arrest. ICSI or in vitro fertilization (IVF) short-term fertilization was performed on M II oocytes with abnormal zona pellucida in controlled superovulation, IVF short-time fertilization failed completely, and Re-ICSI was performed. M I oocytes were performed ICSI/Re-ICSI simultaneously. The ICSI/Re-ICSI fertilization rate, degeneration rate, cleavage rate, high-quality embryo rate and blastocyst rate were compared between the two groups of M II oocytes and M I oocytes, as well as all oocytes M I arrest and part oocytes M I arrest groups, respectively. Results:Totally 37 M II oocytes and 65 M I oocytes underwent ICSI/Re-ICSI. M I oocytes fertilization and 2PN fertilization rates were lower than M II oocytes [46.2%(30/65) vs. 89.2% (33/37); 32.3% (21/65) vs. 83.8% (31/37), all P<0.001]. Both groups had high-quality embryos and blastocyst formation. Compared with part oocytes M I arrest and all oocytes M I arrest, there was no statistical difference in fertilization rate, degeneration rate, high-quality embryo rate and blastocyst formation rate between the two groups (all P>0.05). Conclusion:ICSI/Re-ICSI for patients with abnormal zona pellucida with a high proportion of M I oocytes can increase the patients' oocytes utilization rate and available embryos.

Objective:To explore the pregnancy outcome of intracytoplasmic sperm injection (ICSI)/rescure-ICSI (Re-ICSI) patients with gear-like transparent dense zona pellucida and small perivitelline oocytes.Methods:Totally 6 couples with abnormal zona pellucida came to the Reproductive Medicine Center of Shijiazhuang the Fourth Hospital from January 2015 to June 2020 were retrospectively case control analyzed. A total of 8 cycles had zona pellucida abnormalities, of which 5 couples, the proportion of M I oocytes was ≥50% (part oocytes M I arrest) in 6 cycles and 1 couple (2 cycles) was all oocytes M I arrest. ICSI or in vitro fertilization (IVF) short-term fertilization was performed on M II oocytes with abnormal zona pellucida in controlled superovulation, IVF short-time fertilization failed completely, and Re-ICSI was performed. M I oocytes were performed ICSI/Re-ICSI simultaneously. The ICSI/Re-ICSI fertilization rate, degeneration rate, cleavage rate, high-quality embryo rate and blastocyst rate were compared between the two groups of M II oocytes and M I oocytes, as well as all oocytes M I arrest and part oocytes M I arrest groups, respectively. Results:Totally 37 M II oocytes and 65 M I oocytes underwent ICSI/Re-ICSI. M I oocytes fertilization and 2PN fertilization rates were lower than M II oocytes [46.2%(30/65) vs. 89.2% (33/37); 32.3% (21/65) vs. 83.8% (31/37), all P<0.001]. Both groups had high-quality embryos and blastocyst formation. Compared with part oocytes M I arrest and all oocytes M I arrest, there was no statistical difference in fertilization rate, degeneration rate, high-quality embryo rate and blastocyst formation rate between the two groups (all P>0.05). Conclusion:ICSI/Re-ICSI for patients with abnormal zona pellucida with a high proportion of M I oocytes can increase the patients' oocytes utilization rate and available embryos.

Objective To investigate the clinical effect of anterior controllable antedisplacement and fusion (ACAF) for the treatment of ossification of the posterior longitudinal ligament (OPLL) of the cervical spine.Methods The data of 45 cases with cervical posterior longitudinal ligament ossification treated by ACAF from March 2017 to October 2017 were retrospectively analyzed,including 25 males and 20 females,age 45-68 years,average 57.5 years.There were 18 cases involving C3 vertebral body,30 cases involving C4 vertebral body,40 cases involving C5 vertebral body,34 cases involving C6 vertebral body,and 7 cases involving C7 vertebral body.The function of the neural function was evaluated by the Japanese Orthopaedic Association (JOA) scoring system at preoperation and latest follow-up.The curvature of the cervical spine was measured on the lateral X-ray film of the cervical spine,the maximum occupying ratio of the spinal canal was measured on the cross section of the CT scan,and compression of the cervical spinal cord was evaluated by the cervical MRI.Results Patients were followed up for 3 to 6 months (average,3.9 months).The improvement of neurological function was obtained in all the patients.The JOA score improvement rate at the latest follow-up was 71.3％±9.6％.The cervical lordosis was improved from preoperative 4.5°±3.8° to 10.3°±4.8° at the latest follow-up.The canal stenosis ratio was decreased from preoperative 54.3％±8.2％ to 12.5％±5.3％ at the latest follow-up.MRI showed that the cervical spinal cord was adequately decompressed in situ.No specific complications were identified that were associated with this technique.Conclusion The present study elaborates the surgical tips and demonstrates the satisfactory outcome of ACAF for the treatment of OPLL.This novel technique has the potential to serve as an alternative surgical technique for the treatment of cervical OPLL.

BACKGROUND:Intervertebral disc degeneration is one of the ancient and common clinical diseases. Its complex pathogenesis affected by various factors, such as environment and genes, is stil in debate. Because of the technical limitations, there is stil no deep understanding on the molecular mechanism of intervertebral disc degeneration. However, its molecular mechanism in recent years has made considerable development. OBJECTIVE: To summarize and discuss the molecular mechanism of intervertebral disc degeneration, thereby providing the basis for the effective treatment. METHODS: CNKI and Medline databases were retrieved by the first author using computer to search relevant articles published from 2005 to 2015. The key words were “intervertebral disc degeneration, molecular mechanism, environmental factors, genes, matrix, degradation enzyme,inflammatory factor, biological environment, treatment” in Chinese and English, respectively. Mechanisms of intervertebral disc degeneration, involving genes, cel senescence and apoptosis, degradation enzyme and substrate, inflammatory cytokines, were summarized to explore the pathogenesis and possible effective treatment of intervertebral disc degeneration. RESULTS AND CONCLUSION:Totaly 153 articles were initialy retrieved and finaly 52 articles were included in result analysis according to inclusive and exclusive criteria. Unique structure and biochemical properties of the intervertebral disc are easy to cause intervertebral disc degeneration. Traditionaly, environmental factors, such as occupation and smoking, are considered as the main factors inducing intervertebral disc degeneration; however, more and more studies have shown that genes have the most important influence on intervertebral disc degeneration. Declined extracelular matrix, increased degradation enzymes, and overexpression of inflammatory factors can al destroy the entire structure of intervertebral disc, and accelerate the process of intervertebral disc degeneration. Effective treatment for intervertebral disc degeneration can be formulated depending on the deep understanding on its molecular mechanisms. Although there is a further understanding on the molecular medium of intervertebral disc degeneration, the complex biochemical environment within the intervertebral disc is stil a great chalenge to the treatment of intervertebral disc degeneration.

BACKGROUND: Cervical intervertebral foramen stenosis induced by cervical spondylosis of nerve root type usual y requires surgical treatment. The ways mainly include anterior cervical discectomy and fusion and cervical posterior intervertebral foramen decompression. Which is the best way is stil inconclusive. With innovation, anterior cervical discectomy and fusion for cervical spondylosis of nerve root type has become the mainstream in the current treatment. OBJECTIVE: To study the relationship between curative effects and intervertebral foramen-associated parameter changes in patients with cervical spondylosis of nerve root type after anterior cervical discectomy and fusion. METHODS: From March 2011 to April 2013, 132 patients with cervical spondylosis of nerve root type were treated with anterior cervical discectomy and fusion in the Changzheng Hospital Affiliated to the Second Military Medical University. Neck pain and arm pain visual analogue score, neck disability index score and imaging changes were evaluated before and after treatment. RESULTS AND CONCLUSION: 132 patients were fol owed up for 25(4-28) months. Significant differences in neck pain visual analogue scale, anterior intervertebral disc height, posterior intervertebral disc height, intervertebral foramen height, anterior and posterior diameters of the intervertebral foramen, the area of the intervertebral foramen, and the Cobb angle of the fused segment were detected in al patients before and after treatment (P < 0.05). Posterior intervertebral disc height was positively correlated with intervertebral foramen area (r=0.427, P=0.000). The increased Cobb angle of the fused segment was negatively associated with the size of intervertebral foramen (r=-0.273, P=0.003). Intervertebral foramen area was negatively associated with arm pain visual analogue score (r=-0.502, P=0.000). These results indicated that anterior cervical discectomy and fusion with an interbody fusion cage can obviously enlarge intervertebral foramen in patients with cervical spondylosis of nerve root type, and obtain good curative effect. The size of the intervertebral foramen is negatively related to the axial pain. The reconstruction of the intervertebral disc height is necessary to expand the intervertebral foramen. However, the increase of the curvature fusion segments is not helping to expand the intervertebral foramen.

Human nerve growth factor (NGF) is a nerve cell growth regulation factor, which can provide nutrition for the neurons and promote the neurites outgrowth. In order to produce large-scale recombinant human nerve growth factor (rh-beta-NGF), we constructed a plasmid vector, which can stably express the rh-beta-NGF in the HEK293 cell lines. First, the plasmid of pCMV-beta-NGF-IRES-dhfr was constructed and transformed into HEK293 cells. Then MTX pressurized filter and limiting dilution methods were used to obtain monoclonal HEK293 cell lines. After stepwise reducing serum in culture media, the cells eventually adapted to serum-free medium and secreted rh-beta-NGF. SDS-PAGE analysis revealed that the expression product owned a molecular weight of about 13 kDa and a purity of more than 50%. The peptide mapping sequencing analysis demonstrated the sequences of rh-beta-NGF matched with the theoretical ones. Later we purified this protein by ion exchange and molecular sieve chromatograph. Finally, our experimental results exhibited that the recombinant cell lines can stably express rh-beta-NGF with a high efficiency of more than 20 pg/cell x day. In addition, this protein could successfully induce differentiation of PC12 cells. In summary, our recombinant HEK293 cells can express bio-active rh-beta-NGF with great efficiency and stability, which supply a valid basis to large-scale production of rh-beta-NGF.
Cell Differentiation ; Genetic Vectors ; HEK293 Cells ; Humans ; Nerve Growth Factor ; biosynthesis ; Plasmids ; Recombinant Proteins ; biosynthesis