BACKGROUND:Osteochondral defect of the joint is a difficult problem faced by orthopedic surgeons,and traditional repair methods are difficult to obtain satisfactory curative effects.Hydroxyapatite-polyvinyl alcohol-based composite hydrogel material is a direction of current research. OBJECTIVE:To prepare hydroxyapatite-polyvinyl alcohol/collagen-chitosan-gelatin composite hydrogel material and characterize its physical characteristics,to verify its histocompatibility and cell adhesion and proliferation ability after implantation in vivo,and explore its repair effect on rabbit osteochondral defects. METHODS:The cylindrical porous poly(lactic acid)scaffold was prepared by 3D printing technology(the pore sizes were 1.2,1.4,1.6 and 1.8 mm,respectively).The poly(lactic acid)scaffold was injected with polyvinyl alcohol and hydroxyapatite mixed emulsion.After freezing thawing and dichloromethane dissolution,hydroxyapatite-polyvinyl alcohol hydrogel was prepared.Then,the collagen-chitosan-gelatin mixture was injected into the hydroxyapatite-polyvinyl alcohol hydrogel and crosslinked with genipin.Finally,the hydroxyapatite-polyvinyl alcohol/collagen-chitosan-gelatin composite hydrogel was prepared by alcohol cleaning and freeze-drying.The physical characteristics of the four groups of hydrogels were characterized,and the hydrogels with the best performance were screened for follow-up experiments.Hydroxyapatite-polyvinyl alcohol hydrogel and collagen-chitosan-gelatin composite hydrogel were implanted subcutaneously in SD rats.Hematoxylin-eosin staining and Masson staining were used to observe the adhesion growth of cells on the material surface.Osteochondral defect(diameter:5 mm,depth:6 mm)models were made in the femoral trochlea of bilateral knee joints of 15 rabbits.The composite hydrogel was implanted on the left side(experimental group),while no material was implanted on the right side(control group).Micro-CT and histology were used to evaluate the repair effect of osteochondral defects. RESULTS AND CONCLUSION:(1)Based on the results of porosity,water content,mechanical testing and scanning electron microscopy,it was concluded that the hydroxyapatite-polyvinyl alcohol/collagen-chitosan-gelatin composite hydrogel with a pore size of 1.2 mm was more consistent with the general characteristics of natural cartilage,which was used for subsequent experiments.(2)Hematoxylin-eosin staining and Masson staining exhibited that with the extension of subcutaneous implantation time of the materials,the adhesion of cells around the two materials increased significantly,and the proliferation of cells after the implantation of collagen-chitosan-gelatin was better,a large number of cells could be seen growing into the formed network structure,and the network structure was gradually degraded.(3)In the rabbit osteochondral defect experiment,8 weeks after surgery,Micro-CT examination demonstrated that the material implanted in the experimental group had good integration with the surrounding bone-cartilage,with some bone growth on the surface and inside,while the cartilage and subcartilage in the control group still had obvious defects,without effective repair.Hematoxylin-eosin staining and toluidine blue staining displayed that the composite hydrogel in the experimental group integrated with the surrounding articular cartilage 4-8 weeks after implantation.With the extension of time,new cartilage gradually formed on the surface of the material.At 12 weeks,most of the defect was covered by new cartilage,and good bone growth was also observed in the subcartilage.In the control group,the deep bone defects were mostly repaired and the superficial cartilage and subchondral bone defects were also repaired to a certain extent,but they were mainly replaced by fibrous tissue and part of fibrocartilage 12 weeks after surgery.(4)In conclusion,hydroxyapatite-polyvinyl alcohol/collagen-chitosan-gelatin composite hydrogel material can mimic the structure and function of natural cartilage,and can effectively repair osteochondral defects in animal experiments.

Cells not only contain membrane-bound organelles (MBOs), but also membraneless organelles (MLOs) formed by condensation of many biomacromolecules. Examples include RNA-protein granules such as nucleoli and PML nuclear bodies (PML-NBs) in the nucleus, as well as stress granules and P-bodies in the cytoplasm. Phase separation is the basic organizing principle of the form of the condensates or membraneless organelles (MLOs) of biomacromolecules including proteins and nucleic acids. In particular, liquid-liquid phase separation (LLPS) compartmentalises and concentrates biological macromolecules into liquid condensates. It has been found that phase separation of biomacromolecules requires some typical intrinsic characteristics, such as intrinsically disordered regions, modular domains and multivalent interactions. The phase separation of biomacromolecules plays a key role in many important cell activities. In recent years, the phase separation of biomacromolecules phase has become a focus of research in gene transcriptional regulation. Transcriptional regulatory elements such as RNA polymerases, transcription factors (TFs), and super enhancers (SEs) all play important roles through phase separation. Our group has previously reported for the first time that long-term inactivation or absence of assembly factors leads to the formation of condensates of RNA polymerase II (RNAPII) subunits in the cytoplasm, and this process is reversible, suggesting a novel regulatory model of eukaryotic transcription machinery. The phase separation of biomacromolecules provides a biophysical understanding for the rapid transmission of transcriptional signals by a large number of TFs. Moreover, phase separation during transcriptional regulation is closely related to the occurrence of cancer. For example, the activation of oncogenes is usually associated with the formation of phase separation condensates at the SEs. In this review, the intrinsic characteristics of the formation of biomacromolecules phase separation and the important role of phase separation in transcriptional regulation are reviewed, which will provide reference for understanding basic cell activities and gene regulation in cancer.

Objective:To explore the effects and mechanism of Salvianolic acid B(SalB)on Parkinson's disease(PD).Methods:Forty-eight C57BL/6 male mice were randomly separated into control group(control)withoutdrugs,model group(MPTP)with intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrah-ydropyridine(MPTP),SalB control group with intraperitoneal injection of SalB,and SalB treatment group(MPTP+SalB).Construction of PD mouse model by intraperitoneal injection of MPTP,and treatment with intraperitoneal injection of SalB.Pole climbing test was applied to assess behavior differences.The time of first black stool excretion and water content of feces were measured to evaluate intestinal dysfunctions.The number of tyrosine hydroxylase(TH)positive cells in substantia nigra and the level of Toll like receptor 4(TLR4)in colon were analyzed by immunohistochemistry.The pathological changes of colonic mucosa were observed by HE staining.The levels of calprotectin(CP)and tumor necrosis factor-α(TNF-α)in colon were determined by ELISA.Western blot was used to determine the level of TH in midbrain,the protein level of TH,tight junction protein(ZO-1),and protein level of TLR4/MyD88/NF-κB signaling pathways which express in colon.Results:Com-pared with the Control group,the climbing time,T-turn time and the first black stool excretion time in MPTP group increased while the fecal water content and the number of TH positive cells in substantia nigra were decreased.Accompanied by TLR4 positive cells in colon,pathological injury score of colonic mucosa,levels of CP and TNF-α in colon increased,expression of TH in midbrain and expression of ZO-1 in colon decreased.Expressions of TLR4,MyD88,Nuclear NF-κB p65 and p-NF-κB p65 in colon increased.Com-pared with MPTP group,SalB treatment shortened the climbing time,T-turn time and the first black stool excretion time in SalB treat-ment group,increased the fecal water content and the number of TH positive cells in substantia nigra,lowered TLR4 positive cells in colon,enhanced expression of TH in midbrain and colon,reduced the pathological injury score of colonic mucosa,significantly decreased levels of CP and TNF-α in colon,enhanced expression of ZO-1 in colon,inhibited expressions of TLR4,MyD88,Nuclear NF-κB p65 and p-NF-κB p65 in colon.Conclusion:SalB can protect the nerves and intestines and alleviate the intestinal inflamma-tion of PD mice,which may be related to the inhibition of TLR4/MyD88/NF-κB signal pathway.

Based on the views of FAN's Eight Dynamic-Static Sequential Methods,Professor FAN Guan-Jie believes that the obesity has the pathological factor of blood stasis in addition to qi deficiency and phlegm-damp.The compatibility of blood-activating and stasis-removing drugs for the treatment of obesity is accorded to the progression of the disease.In the clinic,Crataegi Fructus associated medicinal cluster of activating blood and removing stasis is usually recommended.The medicinal cluster is with Crataegi Fructus as the chief medicinal,and is compatible with drug pairs of Salviae Miltiorrhizae Radix et Rhizoma-Carthami Flos and Moutan Cortex-Paeoniae Radix Rubra.Crataegi Fructus associated medicinal cluster is able to treat qi and blood simultaneously,mainly aimed at removing blood stasis,supplemented by nourishing blood,promoting qi and blood movement,and invigorating spleen and stomach,which has the features of simultaneous dispersing and astringency,and proper combination of static therapy and dynamic therapy,and is suitable for obese patients with blood stasis obstruction in the vessels.

AIM: To investigate the clinical efficacy of gonioscopy-assisted transluminal trabeculotomy(GATT)for secondary high intraocular pressure after vitrectomy.METHODS: A retrospective study was conducted on 10 patients(15 eyes)with secondary high intraocular pressure(IOP)after vitrectomy treated with GATT in Department of Ophthalmology, Chengdu First People's Hospital from January 2019 to May 2022. The best-corrected visual acuity(BCVA), IOP, number of IOP-lowering drugs, and complications before operation and at 1d, 1wk, 1, 3 and 6mo after operation were recorded, and the surgical success rate was analyzed.RESULTS:There was no difference in BCVA before and 6mo after operation(Z=0, P=1). The mean IOP decreased from 28.33±9.48mmHg to 17.47±3.78(1d), 18.8±3.29(1wk), 19.13±3.62(1mo), 20.31±3.66(3mo)and 18.03±3.23mmHg(6mo; all P<0.05). The average medication used before surgery was 2(2, 4), and the average medication used 6mo after surgery was 1(0, 2), which was significantly decreased(P<0.001). The total success rate of surgery at 1d, 1wk, 1, 3 and 6mo after surgery was 87%(13 eyes), 93%(14 eyes), 87%(13 eyes), 73%(11 eyes)and 93%(14 eyes)respectively. The main postoperative complications were transient hyphema(10 eyes, 67%)and transient elevated IOP(5 eyes, 33%). No complications seriously affecting the vision occurred.CONCLUSION: GATT is safe and effective in the treatment of secondary high intraocular pressure after vitrectomy.

OBJECTIVES: To explore the sleep status and risk factors for sleep problems in infants and young children in Jilin Province. METHODS: A total of 1 080 healthy infants and young children aged 0-3 years from eight prefecture-level cities and one autonomous prefecture in Jilin Province were selected as subjects. A self-designed questionnaire was used to collect the general information of the subjects, and the Brief Infant Sleep Questionnaire was used to understand the sleep status of the subjects. Multivariate logistic regression analysis was used to analyze the risk factors for sleep problems. RESULTS: The total detection rate of sleep problems in the infants and young children was 38.24% (413/1 080). The total sleep time in the 4-11 month, 12-24 month, and 25-36 month age groups was higher than the recommended total sleep time (P<0.05). Multivariate logistic regression analysis showed that full-term birth, higher educational level of the main caregiver, and higher daytime activity intensity were protective factors for sleep problems in the infants and young children (P<0.05), while lower frequency of vitamin D supplementation, frequent night feeding, and maternal snoring were risk factors for sleep problems (P<0.05). CONCLUSIONS The total sleep time of infants and young children over 4 months old in Jilin Province is higher than the recommended total sleep time, but the prevalence rate of sleep problems is higher. The occurrence of sleep problems is related to various factors. Strengthening follow-up on preterm infants, providing education on infant sleep knowledge to primary caregivers, and regularly supplementing with vitamin D can be beneficial in reducing sleep problems in infants and young children.
Child, Preschool ; Humans ; Infant ; Infant, Newborn ; Cross-Sectional Studies ; Infant, Premature ; Risk Factors ; Sleep ; Sleep Wake Disorders/epidemiology*

Objective: To describe the distribution characteristics of hypertension among adult twins in the Chinese National Twin Registry (CNTR) and to provide clues for exploring the role of genetic and environmental factors on hypertension. Methods: A total of 69 220 (34 610 pairs) of twins aged 18 and above with hypertension information were selected from CNTR registered from 2010 to 2018. Random effect models were used to describe the population and regional distribution of hypertension in twins. To estimate the heritability, the concordance rates of hypertension were calculated and compared between monozygotic twins (MZ) and dizygotic twins (DZ). Results: The age of all participants was (34.1±12.4) years. The overall self-reported prevalence of hypertension was 3.8%(2 610/69 220). Twin pairs who were older, living in urban areas, married, overweight or obese, current smokers or ex-smokers, and current drinkers or abstainers had a higher self-reported prevalence of hypertension (P<0.05). Analysis within the same-sex twin pairs found that the concordance rate of hypertension was 43.2% in MZ and 27.0% in DZ, and the difference was statistically significant (P<0.001). The heritability of hypertension was 22.1% (95%CI: 16.3%- 28.0%). Stratified by gender, age, and region, the concordance rate of hypertension in MZ was still higher than that in DZ. The heritability of hypertension was higher in female participants. Conclusions: There were differences in the distribution of hypertension among twins with different demographic and regional characteristics. It is indicated that genetic factors play a crucial role in hypertension in different genders, ages, and regions, while the magnitude of genetic effects may vary.
Adult ; Female ; Humans ; Male ; Alcohol Drinking ; Diseases in Twins/genetics* ; Hypertension/genetics* ; Twins, Dizygotic/genetics* ; Twins, Monozygotic/genetics*

Objective: To describe the distribution characteristics of hyperlipidemia in adult twins in the Chinese National Twin Registry (CNTR) and explore the effect of genetic and environmental factors on hyperlipidemia. Methods: Twins recruited from the CNTR in 11 project areas across China were included in the study. A total of 69 130 (34 565 pairs) of adult twins with complete information on hyperlipidemia were selected for analysis. The random effect model was used to characterize the population and regional distribution of hyperlipidemia among twins. The concordance rates of hyperlipidemia were calculated in monozygotic twins (MZ) and dizygotic twins (DZ), respectively, to estimate the heritability. Results: The age of all participants was (34.2±12.4) years. This study's prevalence of hyperlipidemia was 1.3% (895/69 130). Twin pairs who were men, older, living in urban areas, married,had junior college degree or above, overweight, obese, insufficient physical activity, current smokers, ex-smokers, current drinkers, and ex-drinkers had a higher prevalence of hyperlipidemia (P<0.05). In within-pair analysis, the concordance rate of hyperlipidemia was 29.1% (118/405) in MZ and 18.1% (57/315) in DZ, and the difference was statistically significant (P<0.05). Stratified by gender, age, and region, the concordance rate of hyperlipidemia in MZ was still higher than that in DZ. Further, in within-same-sex twin pair analyses, the heritability of hyperlipidemia was 13.04% (95%CI: 2.61%-23.47%) in the northern group and 18.59% (95%CI: 4.43%-32.74%) in the female group, respectively. Conclusions: Adult twins were included in this study and were found to have a lower prevalence of hyperlipidemia than in the general population study, with population and regional differences. Genetic factors influence hyperlipidemia, but the genetic effect may vary with gender and area.
Adult ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; China/epidemiology* ; Diseases in Twins/genetics* ; Hyperlipidemias/genetics* ; Metabolic Diseases ; Twins, Dizygotic ; Twins, Monozygotic/genetics*

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.
Mice ; Animals ; Alzheimer Disease/pathology* ; Receptor, Nerve Growth Factor ; Amyloid beta-Peptides ; Autoantibodies ; Mice, Transgenic

[This corrects the article DOI: 10.1016/j.apsb.2021.08.015.].