ObjectiveTo investigate the effects of Zuoguiwan on osteoclast activation induced by breast cancer and its mechanism. MethodsTo simulate breast cancer-induced osteoclastic bone metastasis， RAW264.7 cells were cultured in conditioned medium containing 50% supernatant of MDA-MB-231 breast cancer cells. The dosages of Zuoguiwan used in the experiment were sera containing 5% and 10% Zuoguiwan. Tartrate-resistant acid phosphatase （TRAP） staining was used to detect osteoclast activation. Enzyme-linked immunosorbent assay （ELISA） was used to measure Cathepsin K secretion from RAW264.7 cells. Real-time quantitative polymerase chain reaction （PCR） was used to detect the mRNA expression levels of osteocalcin （OCN） and bone sialoprotein （BSP）. Immunoprecipitation was employed to detect the interaction between Runt-related transcription factor 2 （Runx2） and core binding factor β subunit （CBF-β）. Western blot was used to assess the protein expression of Runx2， phosphorylated Runx2 （p-Runx2）， extracellular signal-regulated kinases 1/2 （ERK1/2）， p-ERK1/2， p38 mitogen-activated protein kinase （MAPK）， p-p38 MAPK， and CBF-β. ResultsCompared with the blank group， the MDA-MB-231 cell supernatant group showed a significant increase in TRAP-positive cell counts and Cathepsin K secretion. Meanwhile， the expression levels of p-Runx2， Runx2-CBF-β interaction， BSP and OCN mRNA， p-p38 MAPK， and p-ERK1/2 proteins were significantly decreased （P<0.01）. Compared with the MDA-MB-231 cell supernatant group， Zuoguiwan-containing sera significantly reduced TRAP-positive cell counts and Cathepsin K secretion （P<0.01）， significantly increased p-Runx2， BSP and OCN mRNA expression， as well as p-p38 MAPK and p-ERK1/2 protein levels， and promoted the interaction between Runx2 and CBF-β （P<0.01）. No significant change in Runx2 expression was observed. Compared to the blank group， the BVD-523 group showed significantly lower expression of p-p38 MAPK and p-ERK1/2 proteins （P<0.01）. Compared with the BVD-523 group， both low and high concentration Zuoguiwan-containing sera groups showed significantly higher p-p38 MAPK expression （P<0.01）， and the high concentration Zuoguiwan group also exhibited a significant increase in p-ERK1/2 expression （P<0.01）， while no statistical difference was found in the low-dose group. ConclusionZuoguiwan inhibits osteoclast activation by inducing phosphorylation of the key transcriptional regulator Runx2 in intra-osteoclast bone formation， and this process is closely associated with the activation of the p38 MAPK/ERK signaling pathway.

Objective:To investigate the quality of life in children with McCune-Albright syndrome (MAS) and its influencing factors, so as to provide scientific basis for improving their quality of life.Methods:The clinical data of 31 children with MAS diagnosed (MAS group) and followed up in Henan Children′s Hospital from June 2015 to December 2021 were retrospectively analyzed.During the same period, 37 healthy age and sex-matched children at a ratio of 1∶1 were recruited as healthy control group.The children′s Quality of Life Universal Core Scale (PedsQL?4.0) was used for the investigation and comparative analysis.Statistical analysis was performed using the independent sample t test, Chi- square test and multiple regression analysis. Results:Compared with the healthy control group, the physiological function ( t=2.092, P<0.05), emotional function ( t=2.373, P<0.05) and total score ( t=2.360, P<0.05) of MAS group significantly decreased.Multiple regression analysis showed that physiological function was negatively correlated with the annual number of vaginal bleeding ( t=-2.367, P<0.05) and the age of first fracture ( t=-2.606, P<0.05). Social function was negatively correlated with the number of fractures ( t=-2.481, P<0.05). Conclusions:The overall quality of life of MAS children is low, especially the quality of physiological function and emotional function.The annual number of vaginal bleedings, the age of the first fracture and the number of fractures are influencing factors for the reduction of the quality of life of children with MAS.

OBJECTIVE: To analyze a child with 11β hydroxylase deficiency (11β-OHD) due to CYP11B2/CYP11B1 chimeric gene. METHODS: Clinical data of the child who was admitted to Henan Children's Hospital on August 24, 2020 were retrospectively analyzed. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. RT-PCR and Long-PCR were carried out to verify the presence of chimeric gene. RESULTS: The patient, a 5-year-old male, had featured premature development of secondary sex characteristics and accelerated growth, and was diagnosed with 21 hydroxylase deficiency (21-OHD). WES revealed that he has harbored a heterozygous c.1385T>C (p.L462P) variant of the CYP11B1 gene, in addition to a 37.02 kb deletion on 8q24.3. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1385T>C (p.L462P) was rated as a likely pathogenic variant (PM2_Supporting+PP3_Moderate+PM3+PP4). The results of RT-PCR and Long-PCR suggested that CYP11B1 and CYP11B2 genes have recombined to form a CYP11B2 exon 1~7/CYP11B1 exon 7~9 chimeric gene. The patient was diagnosed as 11β-OHD and effectively treated with hydrocortisone and triptorelin. A healthy fetus was delivered following genetic counseling and prenatal diagnosis. CONCLUSION 11β-OHD may be misdiagnosed as 21-OHD due to the potential CYP11B2/CYP11B1 chimeric gene, which will require multiple methods for the detection.
Child, Preschool ; Humans ; Male ; Adrenal Hyperplasia, Congenital/genetics* ; Cytochrome P-450 CYP11B2/genetics* ; Exons ; Retrospective Studies ; Steroid 11-beta-Hydroxylase/genetics*

Congenital hydrocephalus is a major neurological disorder with high rates of morbidity and mortality; however, the underlying cellular and molecular mechanisms remain largely unknown. Reproducible animal models mirroring both embryonic and postnatal hydrocephalus are also limited. Here, we describe a new mouse model of congenital hydrocephalus through knockout of β-catenin in Nkx2.1-expressing regional neural progenitors. Progressive ventriculomegaly and an enlarged brain were consistently observed in knockout mice from embryonic day 12.5 through to adulthood. Transcriptome profiling revealed severe dysfunctions in progenitor maintenance in the ventricular zone and therefore in cilium biogenesis after β-catenin knockout. Histological analyses also revealed an aberrant neuronal layout in both the ventral and dorsal telencephalon in hydrocephalic mice at both embryonic and postnatal stages. Thus, knockout of β-catenin in regional neural progenitors leads to congenital hydrocephalus and provides a reproducible animal model for studying pathological changes and developing therapeutic interventions for this devastating disease.
Animals ; Disease Models, Animal ; Hydrocephalus/genetics* ; Mice ; Mice, Knockout ; Neurons ; beta Catenin/genetics*

Objective: To explore the relationship among osteopontin(OPN), Interleukin-17A(IL-17A), anti-MBP auto-antibody and autism spectrum disorder(ASD), and to provide the theoretical basis for the etiology and pathogenesis of ASD. Methods: Forty autistic children and forty matched healthy children were enrolled in this case-control study. The levels of OPN, IL-17A, anti-MBP autoantibody in serum were measured by enzyme-linked immunosorbent assay (ELISA). The associations between those metabolic levels and the severity and intelligence of ASD children were performed by Pearson or Spearman correlation. Results: Children with ASD had higher serum levels of OPN, IL-17A [(296.89±162.95),0.93] pg/mL compared to healthy control[(217.98±113.39), 0.62] pg/mL(P<0.05). Serum OPN, IL-17A, and anti-MBP auto-antibody levels in ASD group were not correlated with the scores of ABC, CARS, and PPVT(P>0.05). However, anti-MBP auto-antibodies level in children with ASD were positively correlated with OPN and IL-17A levels, respectively(r=0.35, 0.34, P<0.05). Conclusion It was obvious that the ASD children were found with neuroimmunologic abnormality, and the underlying mechanism needs to be further explored.

Objective: To understand the status of doctor visit, rehabilitation and foster care of children with autism spectrum disorders in Heilongjiang Province, and to provide a scientific reference for improving ASD rehabitation education system and making the related policies. Methods: Eight autism rehabilitation institutions were selected in Heilongjiang Province by stratified cluster sampling, 357 primary caregivers of ASD children participated in the survey by using the questionnaire "ASD Children’s Rehabilitation Education Status and Needs". Results: The average age of abnormal behavior found of ASD children was (31.08±12.96)months, and the average age of first doctor visit was (35.88±13.20) months, the average age of diagnose was (38.64±13.20) months, and initial rehabilitation was (43.56±16.08)months. The proportion of children who had been diagnosed and have trained in the rehabilitation institutions before the age of 3 years was only 39.0% and 32.0%, respectively. The proportion of rehabilitation out of home town was 47.3%, and rehabilitation >20 hours per week was 73.4%. The proportion of fathers’ and mothers’ work lives affected was 34.5% and 67.8%, respectively, the differences were of statistical signficance(χ2=226.32, P<0.01). About 41.2% of ASD families received government financial support. Conclusion The average age of diagnose is late prolonged, and the proportion of children diagnosed and training before the age of 3 years was relatively low. There were obvious regional differences of rehabilitation education resources distributions of ASD in Heilongjiang Province. The results also demonstrate the need to sustain and enhance the coverage rate of the government financial support.

Objective To explore the integration of the digital imaging medical records system and the hospital information system ( HIS), for a hospital-wide information platform for digital medical records management. Methods All the medical records were classified as " to copy and not to copy" by sampling, and an item corresponding table was developed for both HIS medical record files and imaging records copying types. The imaging copying system for paper-based medical records only covers those must-copy ones, while those medical record files without need to be copied were directly transcoded via the interface to the imaging medical records system from the HIS system. This makes digital imaging medical records complete. Results The digital imaging medical record system is thus integrated, and the cost of making imaging medical records was sizably reduced without compromising the quality and integrity of medical records. Conclusions Imaging medical records produced by copying paper-based ones are integrated with those directly sent via the interface to the imaging medical records system, forming complete digital imaging records, at a much lower cost.

Objective To investigate the relationship of programmed death ligand-1 (PD-L1) with clinicopathological characteristics,radiosensitivity and prognosis of the patients with esophageal squamous cell carcinoma(ESCC). Methods Ninety ESCC patients who received radical radiotherapy diagnosed by ESCC in Affiliated Hospital of North Sichuan Medical College were enrolled. Twenty cases of normal esophageal mucosa were used as the controls. The expression of PD-L1 was detected by using immunohistochemical SP method. Results The expression of PD-L1 protein was not correlated with age, gender, the maximum diameter of tumor, the length of lesion, the local aggressive of tumor, clinical stage and primary tumor volume (all P> 0.05). However, it was statistically correlated with the lymphatic metastasis (χ2= 4.404, P= 0.036). Meanwhile, PD-L1 positive expression was sensitive to radiation(χ2=4.888, P< 0.05). Single factor analysis showed that the maximum diameter of tumor and radiosensitivity were correlated with progression-free survival (PFS) (χ2=6.239,P =0.013;χ2=6.852,P =0.008; χ2= 6.312, P= 0.012) and overall survival (OS) (χ2=8.170, P = 0.004; χ 2= 4.261, P = 0.039; χ2= 5.003, P= 0.025) of ESCC patients. Multifactor analysis showed that the radiosensitivity and the maximum diameter of tumor affected PFS (OR= 0.512, 95 % CI 0.275-0.954, P= 0.035) and OS (OR= 0.507, 95 % CI 0.266-0.968, P= 0.039) in ESCC patients, respectively.Conclusions The level of PD-L1 expression is increased significantly in ESCC tissues compared with the normal esophageal mucosa tissues. PD-L1 may be a novel biomarker for predicting metastatic potential and radiosensitivity in ESCC patients, rather than the prognosis predictors of ESCC patients treated by radiotherapy.

Objective To evaluate the effects of dexmedetomidine on hypoxic pulmonary vasoconstriction and oxygenation during one- lung ventilation (OLV) undergoing esophagectomy. Methods Fifty-six adult patients undergoing esophagectomy and requiring OLV were selected.During inhalational anesthesia with sevoflurane, patients were randomized to receive either dexmedetomidine (dexmedetomidine group,28 patients)or saline placebo(control group,28 patients). The bolus dose of 0.3 μg/kg over 10 min followed by a maintenance dose of 0.6 μg/(kg·h)was used in dexmedetomidine group. The arterial blood gas samples were obtained to evaluate the effects of dexmedetomidine on oxygenation in three times:T1:double-lung ventilation 10 min after anesthetic intubation;T2:OLV 10 min;T3:60 min after continuous infusion of dexmedetomidine. Outcomes included differences in hemodynamic parameters(heart rate and mean arterial pressure), end-tidal sevoflurane concentration, ephedrine dose and atropine dose.Results The levels of pH, arterial partial pressure of carbon dioxide(PaCO2)in two groups had no significant differences(P>0.05).The level of oxygenation index in two groups at T3had significant difference: (153.29 ± 19.00) mmHg(1 mmHg=0.133 kPa)vs. (117.79 ± 12.00) mmHg, 1 mmHg = 0.133 kPa, P < 0.01. At T3, the level of heart rate in dexmedetomidine group was significantly lower than that in control group:(68 ± 11)times/min vs.(89±13)tims/min;meanwhile, the level of end-tidal sevoflurane concentration in dexmedetomidine group was significantly lower than that in control group: (2.9 ± 0.8)% vs. (4.2 ± 0.1)%; there were significant differences (P < 0.01). The ephedrine dose in two groups had no significant difference(P>0.05).Conclusions Dexmedetomidine may provide clinically relevant benefits by improving oxygenation and decreasing the requirement of inhalational anaesthetic agents, thereby limiting its effect on hypoxic pulmonary vasoconstriction during OLV in adults undergoing esophagectomy surgical procedures.

Objective To explore the alteration of the peripheral thyroid hormone level in patients with chronic alcohol dependence and its relationship with depressive emotion.Methods Data were collected from 21 male patients with chronic alcohol dependence (case group) and 21 male health control (control group).Hamilton Depression Scale-24 (HAMD-24) and Alcohol Dependence Screening Scale (MAST) were used.The level of thyroid stimulating hormone (TSH),free triiodothyronine (FT3),free thyroxine (FT4),triiodothyronine (T3) and four iodine thyroxine (T4) of case group and control group were separately determined.The level of above-mentioned hormones and scale score of case group were evaluated in the first and sixth week of the period of temperance.Data of control group were collected once at baseline.Results The level of FT3 in case group was decreased significantly in the first week of the period of temperance compared with the control group ((4.34± 1.01) pmol/L,(5.85 ± 0.78) pmol/L,t =5.56,P＜ 0.01),while the level of TSH in case group was increased((2.62±0.69) uIU/ml,(1.70±0.81)uIU/ml,t=-3.96,P＜0.01).The level of FT3 and T3 in case group decreased significantly in the sixth week of the period of temperance comparedwith the control group(FT3:(5.22±0.92) pmol/L,(5.85±0.78) pmol/L,t=2.45,P＜ 0.05;T3:(1.54±0.54)pmol/L,(1.84±0.34)pmol/L,t=2.92,P＜0.01).The level of FT3 of the case group in the first week decreased significantly compared with the sixth week in the period of temperance (t=-4.12,P＜0.01),while the level of FT4 were increased significantly (t=-3.93,P＜0.01).In case group,the scores of HAMD-24 and the level of T3 (r=-0.465,P＜0.05),TSH (r=-0.489,P＜0.05) were negative correlation in the first week of the period of temperance.No correlation were observed between the score of HAMD-24 and the level of FT3,FT4,TSH,T3,T4 (r=-0.303-0.047,all P＞ 0.05)in the sixth week of the period of temperance.Conclusion The level of serum thyroid is disordered in patients with chronic alcohol dependence.The disorder will recover in the period of temperance and is associated with depressive emotion.