OBJECTIVE To evaluate the ameliorative effect of Juanbi Tongluo Oral Liquid on sciatic neuronal apoptosis in Type 2 diabetic model mice.METHODS The Type 2 diabetes mouse model was established by feeding with high-fat and high-sugar diet combined with intraperitoneal injection of streptozotocin(STZ).The mice were treated with metformin(200 mg·kg-1·d-1),low dose(3.9 g·kg-1·d-1)and high dose(7.8 g·kg-1·d-1)Juanbi Tongluo Oral Liquid for 35 days.The latency of response to thermal stimu-lation was detected by hot plate,and the values of blood glucose insulin and glycosylated hemoglobin were determined.Biochemical kits were used to detect the expression of serum total cholesterol(T-CHO),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px)and oxidation product malondialdehyde(MDA).The expression of tumor cytokine α(TNF-α),interleukin(IL)-1β,IL-6 and IL-10 in serum of mice were detected by ELISA method;the injury of sciatic nerve of model mice was detected by HE staining;the apoptosis of sciatic nerve was detected by TUNEL method;and the expression of neurofilament protein NF-L,apoptosis(cleaved Caspase-3,Caspase-3)and oxidative stress(Nrf2,HO-1)signal pathway proteins in sciatic nerve of model mice were detected by Western blot method.RESULTS High-dose Juanbi Tongluo Oral Liquid shortened the latent period of heat pain response in model mice(P<0.01);downregulated fasting blood glucose and glycated hemoglobin(P<0.01),and upregulated fasting plasma insulin in model mice(P<0.01);downregulated serum T-CHO,TG,and LDL-C levels(P<0.01),upregulated HDL-C levels(P<0.01);downregulated serum pro-inflammatory factors TNF-α,IL-1β and IL-6 levels(P<0.05),upregulated the anti-inflammatory cyto-kine IL-10 level(P<0.01);inhibited sciatic nerve structural damage and apoptosis(P<0.05);downregulated the ratio of cleaved Caspase-3 to Caspase-3 in the apoptosis pathway(P<0.01);upregulated the expression of neurofilament proteins NF-L and NF-H in sciatic nerve tissue(P<0.05,P<0.01);and upregulated the expression of antioxidant stress proteins Nrf2 and HO-1(P<0.01).CONCLUSION Juanbi Tongluo Oral Liquid can improve sciatic neuronal apoptosis of Type 2 diabetic mice,which may be related to its effect on improving oxidative stress and inflammatory stress.

Objective: To investigate vitamin D levels among primary and middle school students in Xicheng District, Beijing Municipality, and to examine the association of vitamin D levels with hemoglobin (Hb) and serum ferritin (SF) levels, so as to provide insights into the prevention of anemia among primary and middle school students. Methods: The first, third and fifth grade primary school students and the first grade junior high school students were sampled from Xicheng District in 2019, using the multistage stratified cluster sampling method, and students' gender, age, height, weight and Hb levels were collected. The 25-hydroxyvitamin D [25-( OH )D] was measured using electrochemiluminescence assay, and SF was detected using immunoturbidimetry. The vitamin D deficiency was determined according to the American College of Endocrinology guidelines. The associations of 25-( OH) D levels with Hb and SF levels were examined using Pearson correlation analysis and Spearman rank correlation analysis. Results: Totally 403 primary and junior high school students were investigated, including 196 boys ( 48.64% ) and 207 girls ( 51.36% ). There were 179, 114 and 110 students at ages of 6 to 8 years ( 44.41% ), 9 to 11 years ( 28.29% ) and 12 to 13 years ( 27.30% ), respectively. The mean 25-( OH )D level was ( 14.80±5.96 ) ng/mL among the study students, and there were 90 students ( 22.33% ) with severe vitamin D deficiency, 243 students ( 60.30% ) with vitamin D deficiency, 63 students ( 15.63% ) with vitamin D inadequacy and 7 students ( 1.74% ) with vitamin D sufficiency. The mean Hb level was ( 136.28±8.33 ) g/L and the median SF level (interquartile range) was 56.80 (14.36) ng/mL among the study students, respectively. The 25-( OH )D level positively correlated with Hb ( r=0.364, P<0.001 ) and SF levels ( rs=0.374, P<0.001 ), and after adjustment for age and body mass index, the 25-( OH )D still correlated positively with Hb ( r=0.157, P=0.048 ) and SF levels ( rs=0.174, P=0.022 ) . Conclusions Vitamin D deficiency is prevalent among primary and middle school students in Xicheng District, and the 25-(OH)-D levels correlate positively with Hb and SF levels. 25-( OH )-D deficiency may contribute to the development of anemia.
vitamin D ; hemoglobin ; serum ferritin ; primary and middle school student

The quality control problems of 49 institutional level medical device clinical trials in hospital from 2016 to 2021 were summarized, and the causes of the problems were analyzed from the perspective of all parties involved in the clinical trial. The improvement measures were discussed, which including improving the management system, strengthening the training of researchers and optimizing the selection method, strengthening the responsibility and regulation consciousness of applicants, and formulating the selection basis of applicants and so on. All the above aims to ensure the quality of clinical trials and provide reference for clinical trial managers and implementers.
Quality Control ; Research Design

OBJECTIVES: Safe and effective anticoagulation is essential for hemodialysis patients who are at high risk of bleeding. The purpose of this trial is to evaluate the effectiveness and safety of two-stage regional citrate anticoagulation (RCA) combined with sequential anticoagulation and standard calcium-containing dialysate in intermittent hemodialysis (IHD) treatment. METHODS: Patients at high risk of bleeding who underwent IHD from September 2019 to May 2021 were prospectively enrolled in 13 blood purification centers of nephrology departments, and were randomly divided into RCA group and saline flushing group. In the RCA group, 0.04 g/mL sodium citrate was infused from the start of the dialysis line during blood draining and at the venous expansion chamber. The sodium citrate was stopped after 3 h of dialysis, which was changed to sequential dialysis without anticoagulant. The hazard ratios for coagulation were according to baseline. RESULTS: A total of 159 patients and 208 sessions were enrolled, including RCA group (80 patients, 110 sessions) and saline flushing group (79 patients, 98 sessions). The incidence of severe coagulation events of extracorporeal circulation in the RCA group was significantly lower than that in the saline flushing group (3.64% vs. 20.41%, P<0.001). The survival time of the filter pipeline in the RCA group was significantly longer than that in the saline flushing group ((238.34±9.33) min vs. (221.73±34.10) min, P<0.001). The urea clearance index (Kt/V) in the RCA group was similar to that in the saline flushing group with no statistically significant difference (1.12±0.34 vs. 1.08±0.34, P=0.41). CONCLUSIONS Compared with saline flushing, the two-stage RCA combined with a sequential anticoagulation strategy significantly reduced extracorporeal circulation clotting events and prolonged the dialysis time without serious adverse events.
Humans ; Citric Acid/adverse effects* ; Prospective Studies ; Sodium Citrate ; Hemorrhage/chemically induced* ; Citrates/adverse effects* ; Anticoagulants/adverse effects* ; Renal Dialysis/adverse effects*

OBJECTIVE: To explore the correlation between the genotypes and metabolic markers and microstructure of bones in children with Gitelman syndrome (GS). METHODS: For 15 children with GS and 10 healthy individuals, baseline data and bone metabolic markers including parathyroid hormone, alkaline phosphatase, osteocalcin, N-terminal propeptide of type I procollagen, beta isomer of the C-terminal telopeptide of type I collagen and 25-hydroxyvitamin D, high-resolution peripheral quantitative computed tomography indicators (volumetric bone mineral density, bone microstructure indicators) were collected. Genetic testing was carried out to determine their genotypes. RESULTS: The volumetric bone mineral density, bone geometry and bone microstructure parameters of the GS group were better than those of the healthy controls (P<0.05). Variants of the SLC12A3 gene were identified in 9 of the 15 patients but none of the 10 healthy controls. CONCLUSION The phenotype of GS children is influenced by the interaction of genetic variants, though the phenotype associated with high frequency mutations showed no specificity. There is also a correlation between their genotype and the bone microstructure.
Biomarkers ; Bone and Bones ; Child ; Collagen Type I/genetics* ; Genotype ; Gitelman Syndrome ; Humans ; Osteocalcin/genetics* ; Peptide Fragments ; Solute Carrier Family 12, Member 3

OBJECTIVE: To explore the genetic basis for a child with 46,XY disorders of sex development (DSD) and explore its genotype-phenotype correlation. METHODS: The child was subjected to whole exome sequencing (WES), and exons 1 to 7 of NR5A1 were subjected to multiplex ligation-dependent probe amplification (MLPA) analysis. RESULTS: The patient presented with rudimentary vulva of a female with Tanner stage 1. B-mode ultrasonography has detected ovary and uterus. The child was found to have a chromosome karyotype of 46,XY. WES revealed that the patient has harbored heterozygous deletion of exon 5 of the NR5A1 gene, which was a novel pathogenic variant inherited from the mother. No abnormality was found in the father. CONCLUSION The main symptoms of 46,XY DSD children are insufficient external genitalia masculinization, for which variants of the NR5A1 gene are an important cause. WES has improved the detection rate of genetic variants and provided a solid basis for genetic counseling of the affected families.
Child ; Disorder of Sex Development, 46,XY/genetics* ; Disorders of Sex Development/genetics* ; Exons/genetics* ; Female ; Genetic Testing ; Heterozygote ; Humans ; Mutation ; Steroidogenic Factor 1/genetics*

Objective:To understand the status of sedation and analgesia treatment and management in pediatric intensive care unit(PICU) in Shandong Province, and to provide the basis for the improvement of sedation and analgesia treatment plan.Methods:This study was a multi-center retrospective study.The PICUs of 6 tertiary hospitals in Shandong Province participated in this study.The data of 1 340 children admitted to these 6 PICUs from January 2016 to December 2018 were collected.The age, gender, the pediatric risk of mortality score Ⅲ at 24 hours after admission, whether they received mechanical ventilation, whether they received sedation and(or) analgesia, whether they were monitored sedation and(or) analgesia, and in-hospital mortality were analyzed.The children were divided into the simple sedation group( n=798), the sedation + analgesia group( n=120) and the non-sedation analgesia group( n=422) according to whether they received sedation and(or) analgesia.The diseases, proportion of mechanical ventilation, incidence of hypotension, average length of stay in PICU and in-hospital mortality were compared among the three groups. Results:The median age of the 1 340 children was (13.3±6.4) months, including 786 males(58.7%). Sedation therapy had been carried out in 6 PICUs, of which 5 PICUs had routine sedation assessment; 4 PICUs had carried out analgesic therapy, of which only 2 had routine pain assessment.A total of 918 children(68.5%)received sedation and(or) analgesia, midazolam was the most commonly used sedative drug, followed by dexmedetomidine, and 526 children(57.3%)were monitored for sedation assessment, the most commonly used assessment method was the Richmond agitation sedation score.One hundred and twenty(9.0%)cases received sedation combined with analgesia, fentanyl was the most commonly used analgesic, and 38 children(31.7%) underwent routine pain assessment.There was no significant difference in age and sex among the three groups.The proportion of surgical diseases and patients received mechanical ventilation(100.0%, 120/120) were the highest in the sedation + analgesia group.The proportion of mechanically ventilated patients was the lowest in the non-sedation analgesia group(11.4%, 48/422). The mean duration of mechanical ventilation in the sedation + analgesia group was slightly shorter than that in the simple sedation group( P>0.05). The incidence of hypotension was highest in the sedation + analgesia group, and lowest in the non-sedation analgesia group[21.7%(26/120) vs.2.1%(9/422), P<0.01]. There was no significant difference in in-hospital mortality and mean PICU stay among three groups. Conclusion:Benzodiazepines are still the main sedative drugs used in PICUs in Shandong Province.In recent years, the usage of dexmedetomidine has gradually increased, but the proportion of analgesic use is very low.At present, analgesic and sedative therapy is mainly used for children after surgery and receiving mechanical ventilation.Although analgesic and sedative therapy does not increase the in-hospital mortality and average length of stay in PICU, it increases the incidence of hypotension.The sedative and analgesic treatment and assessment in the PICU of Shandong Province are still not standardized, mainly reflected in infrequently analgesic treatment and the assessment of sedation and pain, which need to be further improved.

Objective:To explore the needs for discharge plans in patients with ischemic stroke and their family members, and provide a reference for formulating a scientific and standardized discharge plan.Methods:Totally 15 patients with hemiplegia after ischemic stroke admitted in our hospital between January and March 2019 and 15 family members received semi-structured in-depth interviews using phenomenological research methods in qualitative studies. Colaizzi analysis was used to encode, analyze, categorize and refine the data.Results:The needs for discharge plans in patients with hemiplegia after ischemic stroke were summarized into 5 themes, namely, disease knowledge, rehabilitation exercise, psychological support, financial support, and referral services; the needs for discharge plans in family members were summarized into 3 themes, namely, care knowledge/skills guidance, rehabilitation equipment guidance and respite care needs.Conclusions:Patients with hemiplegia after ischemic stroke and their family members have high needs for discharge plans. A personalized multidisciplinary collaborative discharge plan should be provided, and the role of communities in the follow-up rehabilitation treatment should be given full play to.

OBJECTIVE： To investigate the role of clinical pharmacists in the individual anticoagulation of warfarin for the patients with lower extremity venous thrombosis （LEVT） and pulmonary arterial thromboembolism （PATE）. METHODS： Clinical pharmacists participated in individual anticoagulation of warfarin for the patients with LEVT and PATE. It was suggested to detect the gene type of the patient. According to the results of gene test [cytochrome P450 （CYP）2C9*1*1 and vitamin K epoxide reductase complex subunit Ⅰ] and the dose recommended by FDA based on the patient’s gene， the initial dose of warfarin （3.125 mg，once a day） was determined according to the patient’s living habits， height and body mass. Then the maintenance dose of warfarin （the maintenance dose of warfarin was 2.5 mg and 3.125 mg， once a day， alternately taken every other day） was calculated according to the warfarin maintenance dose prediction formula established by Warfarin Pharmaeogenetics Consortium. Pharmaceutical monitoring was conducted， such as INR， prothrombin time and bleeding event monitering. RESULTS： Physicians adopted the suggestion of clinical pharmacists. The maintenance dose of warfarin was 2.5 mg and 3.125 mg， once a day， alternately taken every other day. It was suggested to give Flucloxacillin sodium injection which had less influence on warfarin. The patient recovered well and was discharged. CONCLUSIONS： Based on pharmacogenomics， clinical pharmacists participate in the formulation of individualized anticoagulant regimens for patients， which promote TNR ralue of patients， reduce the risk of early postoperative thromboembolism， and further ensure the safety of drug use in patients.

Objective To investigate the clinical significance of the reconstruction surgery using the toes to repair thumb and fingers defect with the help of the digital technology. Methods Between June, 2012 and May, 2017, 17 partial thumb and finger defects in 12 cases received 3D-CTA assisted finger reconstruction surgeries in us-ing the toe. Preoperative ipsilateral foot 3D-CTA were conducted and the 3D digital models were analyzed. It helped to know the parameters of the move direction and classification of the arteries and veins, etc.It was helpful for design-ing personalized surgical scheme that could match with the length of each finger defect and the defect area and shape in the recipient site of the specific case. Results All 17 toe-to-hand transplants in 12 cases survived. With 6-12 month's followed-up, the appearance of the reconstructed fingers was very closed to the normal fingers. The two-point discrimination was 6-10 mm. According to the upper extremity functional evaluation criteria issued by the Hand Surgery Society of the Chinese Medical Association, the results were rated as excellent in 9 digits, good in 6 digits, fair in 1 digit and poor in l digit. Conclusion The digital technology can help to formulate the operation scheme of personalized and accurate reconstruction of thumb and fingers before the operation.It was helpful to reduce the opera-tion risk and improve the survival rate of fingers reconstruction.It has very good practical and clinical significance.