BACKGROUND:Prolyl hydroxylase domain 2(PHD2)inhibitors can regulate bone metabolism and relieve osteoporosis in ovariectomized rats.cpd17 is a small molecule oral PHD2 inhibitor newly developed by China Pharmaceutical University.It is effective in the treatment of renal anemia with few side effects,but its effect on bone formation and bone resorption is still unclear. OBJECTIVE:To investigate the effects of cpd17 on mouse osteogenic precursor cells. METHODS:Osteogenic precursor cells were treated with cpd17.Alkaline phosphatase activity and extracellular matrix mineralization were measured,and the expression levels of osteogenesis-and osteoclastogenesis-related markers,as well as PHD2 and hypoxia-inducible factor 1α,were detected.After inhibition of the hypoxia-inducible factor 1α pathway using LW6(a hypoxia-inducible factor 1α pathway inhibitor),alkaline phosphatase activity and extracellular matrix mineralization were detected again,as well as the expression levels of osteogenesis-and osteoclastogenesis-related markers,PHD2 and hypoxia-inducible factor 1α. RESULTS AND CONCLUSION:cpd17 significantly enhanced alkaline phosphatase activity and extracellular matrix mineralization,up-regulated the expression of osteogenesis-related markers,down-regulated the expression of osteoclastogenesis-related markers,up-regulated the expression of hypoxia-inducible factor 1α,down-regulate the expression of PHD2.However,cpd17's effects were significantly attenuated by LW6.To conclude,the PHD2 inhibitor cpd17 promotes osteogenic differentiation and inhibits osteoclastic differentiation through activation of the hypoxia-inducible factor 1α signaling pathway.

【Objective】 To investigate the anemia status of infants and toddlers aged 6 - 24 months in Linxia Hui Autonomous Prefecture, Gansu Province, and to comprehensively evaluate the differences in feeding behaviors between anaemic and normal children through the infant and child feeding index (ICFI) and feeding knowledge scores, so as to provide reference for the guidance of infants and young children feeding in ethnic minority areas and the promotion of children′s growth and development. 【Methods】 Taking infants and young children aged 6 - 24 months in Linxia Prefecture as the study subjects, a multi-stage random sampling method was used to select children who met the requirements from 5 townships and 5 villages in 7 counties in 2019 and 2020.Periphral blood samples were collected to test the level of hemoglobin, so as to determine the anemia status.Meanwhile, physical examination was performed and a questionnaire survey of guardians was conducted to analyze the association betweenanaemia and feeding patterns 【Results】 A total of 3 901 infants and children were included in this study, of whom 729 (18.70%) were anaemic, with a mean ICFI score of 12.56±2.70 and a mean feeding knowledge score of 1.97±1.01.There was no statistically significant association of low feeding knowledge score and low ICFI with anaemia after adjusting for confounders (P>0.05), Unqualified meat addition in ICFI was a risk factor for anaemia (OR=1.355, P=0.042), while non-bottle feeding in the past 24 hours (OR=0.762, P=0.021), and breastfeeding in the past 24 hours of infants and toddlers aged 12 - 24 months (OR=0.228, P=0.018) were protective factor for anemia in infants and toddlers aged 12 - 24 months. 【Conclusions】 The average prevalence of anemia in infants and toddlers aged 6 - 24 months in Linxia Hui Autonomous Prefecture of Gansu Province is high, but the level of infant feeding and the level of feeding knowledge of caregivers are low.Early adherence to breastfeeding, timely addition of supplementary food, and more comsumpution of meat for children are conducive to preventing anemia.

BACKGROUND:Due to the sudden release and the rapid removal by proteases,platelet-rich plasma hydrogel leads to shorter residence times of growth factors at the wound site.In recent years,researchers have focused on the use of hydrogels to encapsulate platelet-rich plasma in order to improve the deficiency of platelet-rich plasma hydrogels. OBJECTIVE:To prepare self-assembled polypeptide-platelet-rich plasma hydrogel and to explore its effects on the release of bioactive factors of platelet-rich plasma. METHODS:The self-assembled polypeptide was synthesized by the solid-phase synthesis method,and the solution was prepared by D-PBS.Hydrogels were prepared by mixing different volumes of polypeptide solutions with platelet-rich plasma and calcium chloride/thrombin solutions,so that the final mass fraction of polypeptides in the system was 0.1%,0.3%,and 0.5%,respectively.The hydrogel state was observed,and the release of growth factors in platelet-rich plasma was detected in vitro.The polypeptide self-assembly was stimulated by mixing 1%polypeptide solution with 1%human serum albumin solution,so that the final mass fraction of the polypeptide was 0.1%,0.3%,and 0.5%,respectively.The flow state of the liquid was observed,and the rheological mechanical properties of the self-assembled polypeptide were tested.The microstructure of polypeptide(mass fraction of 0.1%and 0.001%)-human serum albumin solution was observed by scanning electron microscope and transmission electron microscope. RESULTS AND CONCLUSION:(1)Hydrogels could be formed between different volumes of polypeptide solution and platelet-rich plasma.Compared with platelet-rich plasma hydrogels,0.1%and 0.3%polypeptide-platelet-rich plasma hydrogels could alleviate the sudden release of epidermal growth factor and vascular endothelial growth factor,and extend the release time to 48 hours.(2)After the addition of human serum albumin,the 0.1%polypeptide group still exhibited a flowing liquid,the 0.3%polypeptide group was semi-liquid,and the 0.5%polypeptide group stimulated self-assembly to form hydrogel.It was determined that human serum albumin in platelet-rich plasma could stimulate the self-assembly of polypeptides.With the increase of the mass fraction of the polypeptide,the higher the storage modulus of the self-assembled polypeptide,the easier it was to form glue.(3)Transmission electron microscopy exhibited that the polypeptide nanofibers were short and disordered before the addition of human serum albumin.After the addition of human serum albumin,the polypeptide nanofibers became significantly longer and cross-linked into bundles,forming a dense fiber network structure.Under a scanning electron microscope,the polypeptides displayed a disordered lamellar structure before adding human serum albumin.After the addition of human serum albumin,the polypeptides self-assembled into cross-linked and densely arranged porous structures.(4)In conclusion,the novel polypeptide can self-assemble triggered by platelet-rich plasma and the self-assembly effect can be accurately adjusted according to the ratio of human serum albumin to polypeptide.This polypeptide has a sustained release effect on the growth factors of platelet-rich plasma,which can be used as a new biomaterial for tissue repair.

Objective:To explore the efficacy of long intramedullary nails versus short intramedullary nails in the treatment of AO/OTA 31-A3 intertrochanteric fractures.Methods:A retrospective analysis was conducted on 60 patients with AO/OTA 31-A3 intertrochanteric femur fractures treated between March 2019 and August 2022. The patients were randomly divided into two groups (the long nail group and the short nail group). Thirty-four patients were treated with long intramedullary nails, including 16 males and 18 females, aged 68.41±17.84 years old (range 31-96 years). Twenty-six patients were treated with short intramedullary nails, including 13 males and 13 females, aged 72.23±13.97 years old (range 31-90 years). The causes of injury, fracture classification (AO/OTA classification), intraoperative blood loss, operation time, fracture healing time, imaging indexes (fracture reduction quality, postoperative neck trunk angle, and medial support), Harris score of the hip joint at the last follow-up, one-year mortality rates and complications were compared between the two groups.Results:The follow-up time was 24.26±6.67 months in the long nail group and 24.31±5.60 months in the short nail group, and the general information of the two groups were comparable. Between the long nail and short nail group, the intraoperative blood loss was 281.47±235.28 ml vs. 121.92±84.14 ml and the operation time was 110.44±24.63 min vs. 81.15±28.54 min with significant differences ( P<0.05). While the length of hospital stay was 12.35±4.81 d vs. 10.89±4.30 d, the good rate of fracture reduction was 55.9% vs. 61.53%, the fracture healing time was 120.44±16.43 d vs. 128.07±18.33 d, the presence rate of medial support was 67.6% vs. 79.4%, and the excellent rate of Harris score was 65.4% vs. 65.4% with no significant difference between the two groups ( P>0.05). One-year mortality rates was 5.3% vs. 7.1% and complications was 11.7% vs. 15.4% with no significant difference between the two groups ( P>0.05). Conclusion:Both long intramedullary nails and short intramedullary nails are effective in the treatment of AO/OTA 31-A3 intertrochanteric femur fractures. However, surgical time and intraoperative blood loss was less in the short nail group.

Objective:To investigate the clinical efficacy of parathyroidectomy for secondary hyperparathyroidism (SHPT), and to analyze the changes and trends of perioperative intact parathyroid hormone (iPTH), serum calcium and serum phosphorus, and the predictive value of intraoperative parathyroid hormone (ioPTH) measurement for surgical completion. To provide practical theoretical basis and reference for postoperative treatment of SHPT.Methods:Data of 479 SHPT patients admitted to the First Hospital of Harbin from Dec. 2012 to Dec. 2022 were retrospectively analyzed. According to the admission criteria, 457 patients were screened out and divided into PTX group and incomplete PTX group based on whether the level of postoperative parathyroid hormone was reduced to the normal standard. The levels of iPTH, serum calcium and phosphorus during the perioperative period in the two groups were statistically analyzed. SPSS 26.0 statistical software was used for data processing. P<0.05 indicated statistically significant difference. Results:In the analyzed group of 457 patients, the average age was (45.43±11.25) years and the average dialysis age was (90.3±35.8) months. Hypercalcemia, hyperphosphatemia, hyperkalemia and high alkaline phosphatase levels accounted for 41.79%, 94.31%, 20.35% and 75.50%, respectively. Bone loss and osteoporosis accounted for 35.45% and 62.36%, respectively. The incidence of restless leg syndrome was 7.67%. IoPTH and post-operative iPTH level in the PTX group were significantly lower than those in the incomplete PTX group ( P=0.001, P<0.001). IoPTH≤150 pg/mL can predict surgical success, and 58.33% of cases can predict surgical failure by ioPTH being 30% higher than preoperative iPTH. There were significant differences in serum calcium and phosphorus levels between the two groups at 3 hours and 2 days after operation. The incidence of hypocalcemia was 43.19% and 82.49% on the day of operation and within 3 days after operation, and the incidence of hungry bone syndrome was 62.12% in the PTX group. The incidence of postoperative hyperkalemia, arteriovenous fistula thrombosis, temporary hoarseness, bleeding and in-hospital mortality was 43.33%, 1.75%, 0.66%, 0.44% and 0.22%, respectively. Conclusions:Parathyroidectomy is an effective and safe treatment for secondary hyperparathyroidism, and ioPTH plays an important role in predicting the success of surgery. Timely and effective calcium supplementation is an important measure to prevent the serious occurrence and morbidity of bone hunger syndrome.

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*

Objective:To explore the clinical efficacy of disease-modifying drug nusinersen on children with spinal muscular atrophy.Methods:The baseline and longitudinal clinical data of 15 children who were treated with nusinersen in the Children′s Hospital, Zhejiang University School of Medicine from October 2019 to October 2021 were retrospectively collected. The general data (gender, age, genotype, and clinical classification, etc.), motor function, nutritional status, scoliosis and respiratory function were analyzed. Wilcoxon rank-sum test was used for comparing multi-system conditions before and after treatment.Results:The age of 15 cases (7 males, 8 females) was 6.8 (2.8, 8.3) years, with 2 cases of type 1, 6 cases of type 2, and 7 cases of type 3 respectively, and the course of disease was 55.0 (21.0, 69.0) months. After 9.0 (9.0, 24.0) months of treatment, the motor function scale evaluations of the Hammersmith neurological examination section 2 (13.0 (7.0, 23.0) vs. 18.0 (10.0, 25.0) scores, Z=-2.67, P=0.018) of 15 children, the Hammersmith functional motor scale expanded (38.0 (18.5, 45.5) vs. 42.0 (23.0, 51.0) scores, Z=-2.38, P=0.018), and the revised upper limb module (27.0 (19.5, 32.0) vs. 33.0 (22.5, 35.5) scores, Z=-2.52, P=0.012) of children with type 2 and 3 had significantly improved. Thirteen patients achieved clinically significant motor function improvement, and 2 of them had kept stable scale scores. Subjective reports also indicated that the muscle strength and daily exercise ability of these children improved after treatment, and no serious adverse reactions were reported. Supplemented by the multi-disciplinary team management, the levels of some indicators such as Cobbs angle of scoliosis and forced vital capacity all had significantly improved (all P<0.05). Conclusions:Nusinersen can improve the motor function of patients with 5q spinal muscular atrophy, which is also proved safe to be used in children. The drug treatment supplemented by the multi-disciplinary team management is helpful to improve the multi-system function of the children with spinal muscular atrophy.

Objective To compare the clinical characteristics and influence factors of hyperuricemia between genders,in order to provide references for better controlling and preventing the occurrence and development of hyperuricemiaprovide.Methods A total of 5 783 people who underwent physical examination in two Baoding Health Screening Centers from January 1st to June 1st,2016 were enrolled in this study,and all volunteers completed physical examination,laboratory examination and questionnaire survey.Patients with hyperuricemia were selected to analyse the clinical characteristics and influence factors.Results There were statistically significant differences in clinical characteristics,including obesity,blood pressure,blood glucose,blood lipids,liver function,renal function,anemia,blood rheology examination,thyroid ultrasound and lateral radiographs,between male and female patients with hyperuricemia (P＜0.05).The survey showed that there were statistically significant differences in age,education level,marital status,work status,sleeping status,smoking and drinking between male and female patients with hyperuricemia (P＜0.05).The red blood cells counts,marital status and education level were influence factors for female patients with hyperuricemia,while have little effect on male patients.The smoking,creatinine and diastolic blood pressure were influence factors for male patients with hyperuricemia,while have no effect on female patients.Conclusion The clinical characteristics and the influencing factors of male and female patients with hyperuricemia are different,so corresponding preventive and therapeutic measures should be taken for male and female patients.

Objective To investigate the clinical values of continuous hemoperfusion on the level of inter-leukin-18(IL-18)and prognosis in patients with acute paraquat poisoning(APP). Methods A total of 112 pa-tients with APP treated in our hospital from Jun 2013 to Jul 2017 were divided into two groups:control group(56 cases,routine drug and single hemoperfusion)and therapy group(56 cases,treated by continuous hemoperfusion based on control group).All APP patients were treated with continuous veno venous hemofiltration(CVVH)at 24 hours after treatment.Within admission 24 hours,3 days and 7 days after treatment,IL-18,lactic acid(Lac),ar-terial oxygen partial pressure(PaO2),alanine aminotransferase(ALT),creatinine(Cr)and creatine kinase(CK-MB)of patients were detected,28-day survival was recorded.Pearson correlation test was used to analyze the corre-lation between IL-18 in patients with APP and the survival rate. Results In admission,there were no differences in the levels of IL-18,Lac,PaO2,ALT,Cr and CK-MB between the two groups(P>0.05).At 3 days after treat-ment,the levels of IL-18,Lac,ALT,Cr and CK-MB were higher than those before treatment,and the therapy group was lower than the control group,while PaO2was lower than those before treatment,and the therapy group was higher than the control group(P<0.05);At 7 days after treatment,the two groups both had lower levels of IL-18,Lac,ALT,Cr and CK-MB than those after 3 days treatment,and the therapy group was lower than the con-trol group,while PaO2was lower than those after 3 days treatment,and the therapy group was higher than the con-trol group(P<0.05);There were 39 deaths in the therapy group and 49 deaths in the control group,the therapy group had a lower 28-day mortality rate than control group,the difference was statistically significant(69.64% vs 87.50%,χ2=5.303,P=0.021). The level of serum IL-18 in patients with APP was negatively correlated with the survival rate(r =-0.209,P = 0.027).Conclusions Therapeutic effect of continuous hemoperfusion in APP pa-tients is superior to single hemoperfusion. It could decrease the levels of IL-18,Lac,ALT,Cr and CK-MB,im-prove PaO2 and reduce the mortality rate of patients.The clinical curative effect is distinct.

Objective To investigate the iodine intake level and the prevalence of thyroid nodules in Harbin City,and to study the correlation between the concentration of urinary iodine and the prevalence of thyroid nodules.Methods In Harbin,18 communities were randomly selected and specimens were collected from fasting morning urine from 2015 to 2017.The urine iodine concentration (UIC) was detected by arsenic cerium catalytic spectrophotometry,and the thyroid nodule was examined by B ultrasound.Results A total of 2 552 residents aged (45.79 ± 12.06) years old agreed to participate in the study,including 371 males and 2 181 females.The median UIC in all participants was 159.8 μg/L,there was a significant difference in urine iodine frequency distribution among age groups (x2 =40.097,P ＜ 0.01).Furthermore,the median UIC in male was 166.6 μg/L,and in female was 156.2 μg/L.There was a significant difference in UICs between male and female (U =2.122,P ＜ 0.05).The prevalence of total thyroid nodules in all participants was 48.75％ (1 244/2 552),and the standardized rate was 40.55％.Significant difference in the detection rate of thyroid nodules was observed among age groups (x2 =114.922,P ＜ 0.01),and there was a positive and significant correlation between the detection rate of thyroid nodules and increasing age (xtrand =111.746,P ＜ 0.01).Furthermore,in male,41.24％ (153/371) had thyroid nodules,with standardized prevalence rate of 41.13％,and in female,50.02％ (1 091/2 181) had thyroid nodules,with standardized prevalence rate of 49.20％.Likewise,there was a significant difference in the detection rate of thyroid nodules between male and female(x2 =9.790,P ＜ 0.01).The detection rate of thyroid nodules in the iodine deficient population (urinary iodine was 0-＜ 100 μg/L) was 55.58％ (244/439),and the incidence of thyroid nodules in the iodine adequate or optimal population (urinary iodine was 100-＜ 200 μg/L) was 46.68％ (591/1 266).Conclusions The total iodine level of the population in Harbin City of Heilongjiang Province is at adequate level.The detection rate of thyroid nodules is high and it is increased with age.The detection rate of thyroid nodules is higher in female than male.Regular detection of urine iodine and adjusting iodine nutrition will help prevent thyroid nodules.