BACKGROUND:Cartilaginous endplate stromal homeostasis is closely related to intervertebral disc degeneration.Acupotomy that releases posterior wall ligamentum flavum of the interforaminal orifice can improve the symptoms of patients with lumbar disc degeneration.Whether the mechanism of action is related to the regulation of cartilaginous endplate stromal homeostasis remains to be clarified.OBJECTIVE:To investigate the effect of ultrasound-guided needle-knife relaxation of the internal orifice of the rabbit L7/S1 intervertebral foramina on the matrix homeostasis of the rabbit cartilage endplate.METHODS:A total of 24 male New Zealand rabbits were randomly divided into a control group(n=6)and a modeling group(n=18).Lumbar disc degeneration modeling was performed by intermittent standing after transection of the supraspinous interspinous ligament for 12 weeks.After modeling,the modeling group was randomly divided into model group,needle-knife group and fake needle knife group,with 6 rabbits in each group.In the needle-knife group,the ultrasound-guided needle-knife released the ligamentum flavum posterior wall of the right intervertebral foramina,while in the fake needle-knife group,the needle-knife only reached the surface of the posterior wall ligamentum flavum of the intervertebral foramina,with a total of four interventions,each time at an interval of 1 week.No intervention was performed in the control and model groups.Thirty days after the intervention,the disc degeneration was observed by MRI.The morphology of L7/S1 intervertebral disc cartilaginous endplate,nucleus pulposus and annulus fibrosus were observed with hematoxylin-eosin and safranin O-fast green staining and was then scored.The expressions of type II collagen,proteoglycan and matrix metalloproteinase-13 in nucleus pulposus and cartilage endplate of L7/S1 intervertebral disc were detected by immunohistochemistry.RESULTS AND CONCLUSION:MRI results showed that the relative gray value of L7/S1 nucleus pulposus was significantly lower in the model group than in the control group(P<0.01),and higher in the needle-knife group than in the model group and the fake needle-knife group(P<0.05).Hematoxylin-eosin and safranin O-fast green staining showed obvious degeneration of the nucleus pulposus and annulus fibrosus,thinning of the cartilaginous endplate,and obvious calcification at the junction with bone endplate in the model group.The morphology of the cartilaginous endplate and degeneration of the nucleus pulposus were improved in the needle-knife group compared with the model group.The morphological scores of the model group,needle-knife group and fake needle-knife group were significantly higher than those of control group(P<0.01).The morphological score of the needle-knife group was significantly lower than that of the model group and fake needle-knife group(P<0.01).Immunohistochemistry results showed that compared with the control group,the expressions of type II collagen and Aggrecan in the nucleus pulposus and cartilage endplate in the model group and fake needle-knife group were significantly decreased(P<0.01),while the expression of matrix metalloproteinase-13 was significantly increased(P<0.01).Compared with the model group and fake needle-knife group,the expressions of type II collagen and Aggrecan in the nucleus pulposus and cartilage endplate were increased in the needle-knife group(P<0.05),while the expression of matrix metalloproteinase-13 was decreased significantly(P<0.01).In conclusion,the relaxation of the interforaminal orifice by needle knife can regulate the matrix homeostasis of the rabbit cartilage endplate and improve the degeneration of the intervertebral disc.

BACKGROUND:Cartilaginous endplate stromal homeostasis is closely related to intervertebral disc degeneration.Acupotomy that releases posterior wall ligamentum flavum of the interforaminal orifice can improve the symptoms of patients with lumbar disc degeneration.Whether the mechanism of action is related to the regulation of cartilaginous endplate stromal homeostasis remains to be clarified.OBJECTIVE:To investigate the effect of ultrasound-guided needle-knife relaxation of the internal orifice of the rabbit L7/S1 intervertebral foramina on the matrix homeostasis of the rabbit cartilage endplate.METHODS:A total of 24 male New Zealand rabbits were randomly divided into a control group(n=6)and a modeling group(n=18).Lumbar disc degeneration modeling was performed by intermittent standing after transection of the supraspinous interspinous ligament for 12 weeks.After modeling,the modeling group was randomly divided into model group,needle-knife group and fake needle knife group,with 6 rabbits in each group.In the needle-knife group,the ultrasound-guided needle-knife released the ligamentum flavum posterior wall of the right intervertebral foramina,while in the fake needle-knife group,the needle-knife only reached the surface of the posterior wall ligamentum flavum of the intervertebral foramina,with a total of four interventions,each time at an interval of 1 week.No intervention was performed in the control and model groups.Thirty days after the intervention,the disc degeneration was observed by MRI.The morphology of L7/S1 intervertebral disc cartilaginous endplate,nucleus pulposus and annulus fibrosus were observed with hematoxylin-eosin and safranin O-fast green staining and was then scored.The expressions of type II collagen,proteoglycan and matrix metalloproteinase-13 in nucleus pulposus and cartilage endplate of L7/S1 intervertebral disc were detected by immunohistochemistry.RESULTS AND CONCLUSION:MRI results showed that the relative gray value of L7/S1 nucleus pulposus was significantly lower in the model group than in the control group(P<0.01),and higher in the needle-knife group than in the model group and the fake needle-knife group(P<0.05).Hematoxylin-eosin and safranin O-fast green staining showed obvious degeneration of the nucleus pulposus and annulus fibrosus,thinning of the cartilaginous endplate,and obvious calcification at the junction with bone endplate in the model group.The morphology of the cartilaginous endplate and degeneration of the nucleus pulposus were improved in the needle-knife group compared with the model group.The morphological scores of the model group,needle-knife group and fake needle-knife group were significantly higher than those of control group(P<0.01).The morphological score of the needle-knife group was significantly lower than that of the model group and fake needle-knife group(P<0.01).Immunohistochemistry results showed that compared with the control group,the expressions of type II collagen and Aggrecan in the nucleus pulposus and cartilage endplate in the model group and fake needle-knife group were significantly decreased(P<0.01),while the expression of matrix metalloproteinase-13 was significantly increased(P<0.01).Compared with the model group and fake needle-knife group,the expressions of type II collagen and Aggrecan in the nucleus pulposus and cartilage endplate were increased in the needle-knife group(P<0.05),while the expression of matrix metalloproteinase-13 was decreased significantly(P<0.01).In conclusion,the relaxation of the interforaminal orifice by needle knife can regulate the matrix homeostasis of the rabbit cartilage endplate and improve the degeneration of the intervertebral disc.

OBJECTIVE To study pharmaceutical management provisions in the Evaluation Standards for Third-level Maternal and Child Health Care Hospitals in Hubei Province (2024 Edition) (hereinafter referred to as 2024 Edition of Hubei Maternal and Child Health Care Standards). METHODS The formulation of pharmaceutical management clauses and management rules in the 2024 Edition of Hubei Maternal and Child Health Care Standards was elaborated and compared with the pharmaceutical management clauses in the Evaluation Standards for Third-level Maternal and Child Health Care Hospitals (2016 Edition) to find out their similarities and differences;the basis for the formulation of unique pharmaceutical management clauses was analyzed,so as to propose further improvement suggestions. RESULTS & CONCLUSIONS Compared with the Evaluation Standards for Third-level Maternal and Child Health Care Hospitals (2016 Edition),the similarities in pharmaceutical management in the 2024 Edition of Hubei Maternal and Child Health Care Standards were mainly reflected in the relevant laws,regulations,rules and personnel requirements that should be followed,the full process management of drug procurement,reserve,storage and recall,drug dispensing and formulation management,etc. The unique provisions of the 2024 Edition of Hubei Maternal and Child Care Standards were mainly reflected in the establishment of children's medication working group,the establishment of a list of children's specific drugs,the development of surplus drug management system,and the management of off-label drug use,etc. The formulation of unique provisions for pharmaceutical management not only conformed to the newly released policy requirements in recent years,but also combined the characteristics and actual situation of maternal and child health care hospitals. 2024 Edition of Hubei Maternal and Child Health Care Standards should be further improved in terms of strengthening detail management and enhancing the rational application management of traditional Chinese medicine.

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

OBJECTIVE To investigate the development of individual therapy of antimicrobial agents in pediatric patients. METHODS A questionnaire survey was conducted to investigate the individual therapy of antimicrobial agents in 30 children’s hospitals and pediatric departments of general hospitals in China. The survey data was analyzed statistically by Microsoft Excel 2007 and SPSS 26.0 software. RESULTS In this survey， 75 questionnaires were collected， and 53 of them were valid with an effective rate of 70.7%. The results showed that 86.7% （26/30） of the hospitals carried out individual therapy of antimicrobial agents in different forms. Clinical needs primarily contributed to the individual therapy in these hospitals， while the insufficient personnel and equipment were the biggest obstacles for individual therapy. The proportions of hospitals， who implemented evidence- based pharmacy， therapeutic drug monitoring （TDM）， model-informed precision dosing （MIPD） and antimicrobial-related genetic tests were 70.0%， 80.0%， 30.0% and 33.3%， respectively. Various detection methods of TDM were carried out in various hospitals， and the antimicrobial agents which needed TDM focused on vancomycin and voriconazole. Moreover， nearly half of pharmacists did not know much about MIPD. CONCLUSIONS At present， TDM is the main way to develop individual therapy of antimicrobial agents in various hospitals， but its monitoring coverage and testing standards need to be improved. MIPD and antimicrobial-related gene tests still need to be further promoted in clinical practice.

Tic disorders, which are mainly characterized by motor and/or vocal tics, are common pediatric neuropsychiatric disorders.Pharmacotherapy is an important part of the management of tic disorders.In addition to the individualized grasp of its indications, medicine selection also needs to weigh the risks and benefits.This article made an overview and evaluation of pharmacological treatments for children with tic disorders, so as to acquire the best available evidence on the efficacy and safety of the relevant medicines and to improve clinical decision-making.

Objective To investigate the relationship between serum 10-hydroxycarbazepine (MHD, the main active metabolite of oxcarbazepine) concentration and oxcarbazepine efficacy and safety, and to optimize rational use of oxcarbazepine. Methods A total of 553 patients were enrolled in a self-controlled and open-label trial to assess the efficacy and safety of oxcarbazepine as monotherapy. The steady state serum MHD trough concentrations after dose were determined by SPE-HPLC. The relationship between MHD level and efficacy were evaluated by logistic regression model and receiver operating characteristic (ROC) curve. Results A total of 498 patients (90.1%) were effective and 404 patients (73.1%) were seizure free after oxcarbazepine monotherapy in this study. The clinical therapeutic range of steady state serum MHD trough concentrations observed in this study was 5 - 20 mg ? L-1 , and the corresponding 95% distribution interval of oxcarbazepine daily dose was 9. 0 -34.5 mg?kg-1?d-1 . Logistic regression results indicated a positive correlation of antiepileptic efficacy with serum MHD trough concentration within 0.9-30.0 mg?L-1 . The ROC area (95% confidence interval) of MHD trough concentration as the predictor for efficacy was 0.964 (0.938- 0.990), which showed accurate predictions. Most of patients whould have good antiepileptic efficacy while the steady-state serum MHD trough concentration remains above 8 mg?L-1 . Adverse effects were observed in 104 patients (18.8%) during oxcarbazepine dose escalation phase, and 23 patients (4.2%) during maintenance phase. There were no severe adverse effects associated with oxcarbazepine in this study. Patients with serum MHD concentrations >20 mg?L-1 were at greater risk of developing adverse effects. Conclusion Oxcarbazepine therapeutic efficacy and safety are associated with MHD trough level closely, so it is necessary to monitor MHD concentration.

Objective To investigate the relationship between severe toxicity during high-dose methotrexate (HD-MTX) chemotherapy and 29 related factors including SLCO1B1 521T ＞ C genovariation,and to enhance drug safety.Methods Eighty-two children with acute lymphoblastic leukemia (ALL) received HD-MTX chemotherapy.The regimen was MTX 3-5 g/m2 continuous infusion for 24 hours.The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to detect the patients' genotypes of SLCO1B1 T521C polymorphism,which was the coding gene of organic anion transporting polypeptide 1 B1 (OATP1 B1).Haematological,gastrointestinal and hepatic toxicities in 1-10 days after HD-MTX administration were observed and graded according to Common Terminology Criteria for Adverse Events (CTCAE,version 4.02).The patients were divided into two groups based on toxicity grades:case group (grades Ⅲ-Ⅴ) and normal group (grades 0-]]).The differences of 29 variates including biology features,biochemical indicators,SLCO1B1 T521 C polymorphism and etc.were compared between the two groups by univariate analysis,and the significant factors were found out.The final predictive model of severe HD-MTX-related toxicity was set up through Logistic regression analysis.Receiver operating characteristic (ROC) curve of predictor was drawn based on final model in order to evaluate its predictive ability.Results There were only 4 significant different variates between case group and normal group (P ＜ 0.05),including SLCO1B1 T521C polymorphism,serum MTX concentrations at 72 hours after starting MTX infusion (C72h),the ratios of 7-hydroxy-MTX (the metabolin of MTX) to MTX concentrations at 48 hours (k48 h),and frequency of k48 h ≤2.Based on a multivariate logistic regression analysis,only SLCO1B1 521T＞ C genovariation (odds ratio 18.489,95％ confidence interval 5.413-63.157)was the significant independent predictor for severe HD-MTX-related toxicity.The area under ROC (95％ confidence interval) of SLCO1B1 521T ＞ C genovariation as the predictor for severe HD-MTX-related toxicity was 0.776 (0.653-0.899),which had significant diagnositic value (P ＜ 0.05).Conclusions There is higher risk of severe HD-MTX-related toxicity while patients having SLCO1B1 521T ＞ C genovariation.Clinician should consider it and take some protective measures.

Objective To recheck the reliability of methotrexate ( MTX) serum concentration at 48 h ( C48 h ) in predicting the pharmacokinetic characteristics and toxic reactions at terminal elimination phase after high dose MTX infusion and to provide a reference for determination of rational rescue regimen in clinic practice. Methods In total,114 cases of children with acute lymphoblastic leukemia (ALL) received 176 courses of high dose MTX chemotherapy treatment. The regimen was continuous infusion of MTX[3 -5 g·( m2 ) -1 ] in 24 h. Plasma samples were treated with solid phase extraction and serum concentrations of MTX were determined by HPLC at 24,48 and 72 h (C24 h ,C48 h and C72 h ) after starting MTX infusion. All data were divided into C48 h≥1 μmol·L-1 group and C48 h<1 μmol·L-1 group. The pharmacokinetic parameters of the two groups at elimination phase were estimated by residual method and the toxic reactions after MTX infusion of two groups were compared by Ridit analysis. Results The C72 h and AUC48-∞ were significantly higher in C48 h ≥1 μmol · L-1 group than in C48 h <1 μmol·L-1 group (P<0. 01). The MTX toxicities to the blood,digestive and hepatic systems were significantly higher in C48 h≥1 μmol·L-1 group than in C48 h < 1 μmol · L-1 group ( P < 0. 05). Conclusion C48 h can predict the pharmacokinetic characteristics and toxic reactions at ther terminal elimination phase. Therefore,C48 h≥1 μmol·L-1 can be used as a marker of MTX elimination delay event to guide later rescue regimen.

Objective To evaluate guglidnai detachable ceil(GDC)embolization therapy in treatment of acnte stage ruptured aneurysms.Methods 86 patients were involved in our study,we treat aneurysms with different intravascular therapy techniques,anti-artery-spasm treatment and lumber centesis were performed after therapy.Resuits 72 patients received 100% embolization,10 patients received 95% embolization,4 patients received 90% embolization,no patient died due to therapy in follow-up,further function recover was found.Conclusion Acute stage intravascular therapy combined with comprehensive measures can effectively improve the outcome of patients with ruptured aneurysms.