OBJECTIVE To investigate the effect of pharmaceutical services guided by root cause analysis （RCA） in a problem-oriented manner combined with knowledge-attitude-practice （KAP） theory on reducing the incidence of protocol violations of investigational medicinal products in pediatric clinical trials. METHODS A total of 617 participants from 69 drug clinical trial projects conducted in our hospital from January 2016 to December 2020 were selected as the control group， and 868 participants from 72 drug clinical trial projects from January 2022 to December 2025 as the observation group. RCA was performed on the protocol violations of investigational medicinal product in the control group to identify the types and underlying causes. The control group received routine pharmaceutical services for drug clinical trials， while the observation group was provided with precision pharmaceutical services from the three dimensions of knowledge， attitude and practice on the basis of routine pharmaceutical services， according to the root causes identified by RCA. The occurrence of investigational medicinal products protocol violations was compared between the two groups. RESULTS The total incidence of protocol violations of investigational medicinal products， as well as the incidences of minor and major protocol violations， were all significantly lower in the observation group than in the control group （ P ＜0.001）. The main types of protocol violations in both groups included missed/under-/over-dosing of medications， non-adherence to administration time， failure to adjust dosage as required， and combined medication/vaccination in violation of the protocol. Regarding the responsible subjects of protocol violations， the incidences of protocol violations attributed to participants and their guardians as well as investigators and accidental factors were significantly lower in the observation group than in the control group （ P ＜0.001， P ＜0.001， P ＝0.025）. However， there were no statistically significant differences in the incidences of protocol violations caused by sponsor-related reasons between the two groups （ P ＞0.05）. CONCLUSIONS Pharmaceutical services led by pharmacists， based on problem-oriented RCA and combined with KAP theory， can effectively reduce the protocol violations of investigational medicinal products rate in pediatric clinical trials， thereby safeguarding the safety and rights of study participants.

AIM:To investigate the expression of centromere protein-H(CENP-H)in adrenocortical carcino-ma(ACC)and its relationship with disease progression and prognosis,and to explore the impact of CENP-H gene knock-down on the viability and migration of ACC cells.METHODS:The mRNA expression level of CENP-H in 76 ACC pa-tients and 128 healthy controls,and its correlations with tumor stages and prognosis were analyzed by GEPIA2 database.The mRNA expression of CENP-H in different stages of ACC and its correlation with disease prognosis were further ana-lyzed by ULCAN database.The protein expression of CENP-H was examined by immunohistochemical staining of paraffin-embedded ACC and normal adrenal gland specimens.Knockdown of CENP-H by siRNA(siCENP-H)was performed in human ACC cell line H295R.The viabilty of H295R cells transfected with siCENP-H or siNC was measured by CCK-8 as-say,the cell migration was detected by wound-healing assay,and the protein levels of CENP-H,p-ERK1/2,t-ERK1/2,p-P38,t-P38,p-JNK1/2 and t-JNK1/2 were detected by Western blot.RESULTS:The mRNA level of CENP-H was signifi-cantly higher in ACC than that in normal controls,and was correlated with tumor stages and prognosis.The protein level of CENP-H was significantly higher in ACC specimens than that in normal adrenal gland.Knockdown of CENP-H in H295R cells resulted in decreased cell viability and migration.The protein levels of p-P38 and p-JNK1/2 were decreased in si-CENP-H group.CONCLUSION:CENP-H is highly expressed in ACC,and is correlated with tumor stages and poor prognosis.Knockdown of CENP-H can inhibit the viability and migration of ACC cells,and its mechanism may related to inactivation of P38 and JNK signaling pathways.

The difficulty in the treatment of diabetic foot lies in the high rate of recurrence and difficulty in eradicating the disease, and the results of both systemic basic treatment and local surgical treatment are not ideal. In recent years, domestic scholars have applied tibial transverse transport for the treatment of diabetic foot. Tibial transverse transport is suitable for the treatment of severe diabetic foot with a good blood supply of the large and middle arteries. It has the advantages of high healing rate and low recurrence rate, and can effectively reduce the mortality and amputation rate of patients. However, postoperative complications such as tibial osteotomy fracture, pin tract infection, skin necrosis at osteotomy area, tibial deformity and osteomyelitis should be paid attention to. Domestic scholars have improved the operation of tibial transverse bone transport in terms of reducing the surgical incision, osteotomy area, and preserving the blood supply of the osteotomy site. The modified double bone flap transverse tibial bone transport and "door" shaped window technique have been derived, and related surgical instruments have also been improved in the direction of precision. At present, the research on the mechanism of tibial transverse transport in the treatment of diabetic foot mainly focuses on promoting the reconstruction of macrophage polarization balance, stem cell mobilization and angiogenesis. After tibial transverse transport, the polarization of macrophages to classical activated type was decreased, and the polarization of selective activated type was increased. The two mechanisms promoted each other to reconstruct the polarization balance of macrophages. Bone transport activated SDF-1/CXCR4/PI3K/AKT and Wnt signaling pathways to induce stem cell mobilization. At the same time, it stimulates the release of angiogenic factors, activation of endothelial progenitor cells and Ras/Raf/MEK/ERK signaling pathways to promote angiogenesis and ultimately promote the healing of diabetic foot ulcers.

The difficulty in the treatment of diabetic foot lies in the high rate of recurrence and difficulty in eradicating the disease, and the results of both systemic basic treatment and local surgical treatment are not ideal. In recent years, domestic scholars have applied tibial transverse transport for the treatment of diabetic foot. Tibial transverse transport is suitable for the treatment of severe diabetic foot with a good blood supply of the large and middle arteries. It has the advantages of high healing rate and low recurrence rate, and can effectively reduce the mortality and amputation rate of patients. However, postoperative complications such as tibial osteotomy fracture, pin tract infection, skin necrosis at osteotomy area, tibial deformity and osteomyelitis should be paid attention to. Domestic scholars have improved the operation of tibial transverse bone transport in terms of reducing the surgical incision, osteotomy area, and preserving the blood supply of the osteotomy site. The modified double bone flap transverse tibial bone transport and "door" shaped window technique have been derived, and related surgical instruments have also been improved in the direction of precision. At present, the research on the mechanism of tibial transverse transport in the treatment of diabetic foot mainly focuses on promoting the reconstruction of macrophage polarization balance, stem cell mobilization and angiogenesis. After tibial transverse transport, the polarization of macrophages to classical activated type was decreased, and the polarization of selective activated type was increased. The two mechanisms promoted each other to reconstruct the polarization balance of macrophages. Bone transport activated SDF-1/CXCR4/PI3K/AKT and Wnt signaling pathways to induce stem cell mobilization. At the same time, it stimulates the release of angiogenic factors, activation of endothelial progenitor cells and Ras/Raf/MEK/ERK signaling pathways to promote angiogenesis and ultimately promote the healing of diabetic foot ulcers.

Objective To develop a framework and indicators system for disability-related service data in China. Methods Using International Classification of Functioning, Disability and Health (ICF) framework and approach, the framework and indicators system were developed using content analysis, logical reasoning and expert consultation. Results A system with nine aspects, 35 dimensions and 115 indicators was established. Eleven experts with disability-related background all accepted the system, and satisfied in the importance and operability.Conclusion A data framework and indicators system with nine aspects, 35 dimensions and 115 indicators has been established for disability-related service, which can be used in further data collection.

ObjectiveTo investigate the relationship between microalbuminuria (MAU) and short-term outcome in patients with acute ischemic stroke.MethodsThe consecutive patients with acute ischemic stroke admitted to hospital were enrolled prospectively.The first urine specimen was taken on the following morning after admission for detecting urine albumin/creatinine ratio (UACR).UACR 30-300 mg/g was defined as MAU positive.Stroke severity was evaluated with the National Institutes of Health Stroke Scale (NIHSS) at admission and the modified Rankin Scale (mRS) was used to evaluate functional outcome at discharge, and good outcome was defined as mRS score of 0 to 2.ResultsA total of 244 patients with acute ischemic stroke were enrolled, including MAU positive in 53 patients (27.12%), and poor outcome in 67 patients (27.50%).Univariate analysis showed that age, baseline NIHSS score, systolic blood pressure, fasting blood glucose, globulin, D-dimer, white blood cell count, neutrophils, and the proportions of ischemic heart disease in patients of the MAU positive group were significantly higher than those of the MAU negative group (all P<0.05).Multivariate logistic regression analysis showed that MAU (odds ratio [OR] 1.520, 95% confidence interval [CI] 1.151-1.794;P=0.031), baseline NIHSS score (OR 1.570,95% CI 1.357-1.808;P<0.001) were the independent risk factors for short-term poor outcome in patients with acute ischemic stroke.ConclusionsThe incidence of MAU is high in patients with acute ischemic stroke.MAU positive can be used as one of the independent predictors of short-term poor outcome in patients with acute ischemic stroke.

OBJECTIVETo observe the efficacy of fenofibrate for hepatic steatosis in rats after severe burn.

METHODSTwenty-seven male SD rats were divided into sham injury group, burn group, and burn+ fenofibrate group according to the random number table, with 9 rats in each group. Rats in sham injury group were sham injured on the back by immersing in 37 ℃ warm water for 15 s and then remained without other treatment. Rats in burn group and burn+ fenofibrate group were inflicted with 30% total body surface area full-thickness scald (hereinafter referred to as burn) on the back by immersing in 98 ℃ hot water for 15 s, and then they were intraperitoneally injected with lactated Ringer's solution at post injury hour (PIH) 1. From PIH 24 to post injury day (PID) 8, rats in burn+ fenofibrate group were treated with fenofibrate in the dose of 80 mg·kg(-1)·d(-1), while those in burn group were treated with equivalent volume of saline. (1) Three rats of each group were respectively selected on PID 4, 6, and 8 for the collection of inferior vena caval blood samples. Serum content of total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), high density lipoprotein (HDL), and low density lipoprotein (LDL) was determined with fully automatic biochemical analyzer. Body mass of each rat was measured immediately after blood sampling, and then rats were sacrificed to collect liver tissue for weighing wet mass. The ratio of wet mass of liver tissue to body mass (liver index) was calculated. Meanwhile, gross observation of liver was performed. (2) One liver tissue sample was harvested from each rat at each time point to observe histopathologic changes with HE staining. One liver tissue slice of each rat at each time point was collected to evaluate degree of hepatic steatosis, and the number of rats in each group in each grade of hepatic steatosis was recorded. Measurement data were processed with analysis of variance of factorial design and SNK test, and enumeration data were processed with Kruskal-Wallis test and Nemenyi test.

RESULTS(1) The content of TC, TG, FFA, and HDL of rats in burn group on PID 4 was obviously different from that in sham injury group (with P values below 0.05). Compared with that in burn group, the content of TC, TG, and FFA of rats was significantly decreased (with P values below 0.05), while the content of HDL of rats was not obviously changed in burn+ fenofibrate group on PID 4 (P>0.05). There were no obvious differences in the content of LDL of rats among 3 groups on PID 4 (with P values above 0.05). The content of TC, TG, and HDL of rats in burn group on PID 6 was obviously different from that in sham injury group (with P values below 0.05). Compared with that in burn group, the content of TC and TG of rats was significantly decreased (with P values below 0.05), while the content of HDL of rats was significantly increased in burn+ fenofibrate group on PID 6 (P<0.05). There were no obvious differences in the content of FFA and LDL of rats among 3 groups on PID 6 (with P values above 0.05). The content of TC and HDL of rats in burn group on PID 8 was obviously different from that in sham injury group (with P values below 0.05). Compared with that in burn group, the content of TC of rats was significantly decreased (P<0.05), while the content of HDL of rats was not obviously changed in burn+ fenofibrate group on PID 8 (P>0.05). There were no obvious differences in content of TG, FFA, and LDL of rats among 3 groups on PID 8 (with P values above 0.05). (2) The texture of liver tissue of rats in burn+ fenofibrate group at each time point was tender and soft, without oil or fat on the section, which was close to the gross condition of liver of rats in sham injury group. Dark yellow plaque scattered on the surface of liver tissue of rats in burn group at each time point with oil and fat on the section, which was especially obvious on PID 6. There was no obvious difference in liver index of rats among 3 groups on PID 4 (F=1.63, P>0.05). On PID 6 and 8, the liver indexes of rats in sham injury group, burn group, and burn+ fenofibrate group were 0.0416±0.0016, 0.0533±0.0054, and 0.0370±0.0069; 0.0423±0.0034, 0.0624±0.0005, and 0.0444±0.0042 respectively. The liver indexes of rats in burn group on PID 6 and 8 were significantly higher than those in the other two groups (with P values below 0.05). There were no obvious differences in the liver indexes of rats between burn+ fenofibrate group and sham injury group on PID 6 and 8 (with P values above 0.05). (3) The liver tissue structure of rats in sham injury group was normal at each time point. Hepatic steatosis of rats in burn group at each time point appeared microvesicular and disperse, which was especially obvious on PID 6. Mild hepatic steatosis was observed in rats of burn+ fenofibrate group on PID 4, and then the structure of liver tissue gradually recovered to normal level from PID 6 on. The degree of hepatic steatosis of rats in sham injury group was 0 grade. One rat in I grade, 1 rat in II grade, and 7 rats in III grade were observed in hepatic steatosis of rats in burn group. Three rats in 0 grade, 4 rats in I grade, and 2 rats in II grade were observed in hepatic steatosis of rats in burn+ fenofibrate group. The degree of hepatic steatosis of rats in burn group was more severe than that in the other two groups (with χ(2) values respectively 56.25 and 162.44, P values below 0.05). The degree of hepatic steatosis of rats in burn+ fenofibrate group was more severe than that in sham injury group (χ(2)=27.51, P<0.05).

CONCLUSIONSFenofibrate can ameliorate the dyslipidemia of severely burned rat, and it can alleviate the degree of hepatic steatosis in certain degree.

Animals ; Burns ; pathology ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Dyslipidemias ; drug therapy ; Fatty Acids ; blood ; Fenofibrate ; pharmacology ; Liver ; pathology ; Liver Cirrhosis ; drug therapy ; Male ; Rats ; Rats, Sprague-Dawley ; Triglycerides ; blood

Diverticulum ; diagnosis ; Eyelids ; pathology ; Fistula ; diagnosis ; Humans ; Infant ; Male

Background Malignant osteopetrosis is an extremely rare dense bone disease,and sometimes features ocular disease and cranial nerve palsy.This disease received high attention because of its poor prognosis.And whether the eye manifestation improved after treatment is a problem for concern.Objective This study was to clarify the clinical manifestation,treatment and prognosis of malignant osteopetrosis associated with ocular disease.Methods A retrospective study was adopted.Two children with malignant osteopetrosis associated with eye symptoms were collected from Beijing Children Hospital.The systemic and ocular medical examinations were performed on the patients,including physical examination,hematology laboratory examination,abdominal B ultrasound and bone X ray radiography,external ocular examination,flash visual evoked potential (F-VEP) and CT of orbit.Bone marrow hematopoietic stem cell transplantation was employed and 5-year following-up was cinducted on the chidren.Results The children showed increased bone density,systemic bone sclerosis,basilar thickening,abnormalities of hematology indexes,anemia,hepatosplenomegaly,optical canal stenosis and abnormality of F-VEP P2 wave.In addition,optical disc pale,facial paralysis and paralytic esotropia were seen in a female child and alternating strabismus was found in another boy.After successful treatment,the systemic symptoms remitted in both children,but the eye findings remained unchanged in the female child during the follow-up duration.However,the strabismus diminished in the male child.The optical bone canal widening to 1.9 mm 1 year and 3.2 mm 5 years after treatment in the female child.Conclusions Strabismus and eye disease are the signs of malignant infantile osteopetrosis and reflections of the impairment of the central nervous system.The pathogenetic mechanism of malignant osteopetrosisrelated eye disease is below understanding now.Early bone marrow hematopoietic stem cell transplantation for malignant osteopetrosis can offer the best chance of long-term survival and improve the prognosis of eye diseases.