OBJECTIVE: To investigate the impact of bone mass and volume of low-density zones beneath the tibial plateau on the maximum von Mises stresses experienced by the cartilage and meniscus in the knee joint. METHODS: The study included one healthy adult volunteer, from whom CT scans were obtained, and one patient diagnosed with knee osteoarthrisis (KOA), for whom X-ray films were acquired. A static model of the knee joint featuring a low-density zone was established based on a normal knee model. In the finite element analysis, axial loads of 1 000 N and 1 800 N were applied to the weight-bearing region of the upper surface of the femoral head for model validation and subsequent finite element studies, respectively. The maximum von Mises stresses in the femoral cartilage, as well as the medial and lateral tibial cartilage and menisci, were observed, and the stress percentage of the medial and lateral components were concurrently analyzed. Additionally, HE staining, as well as alkaline magenta staining, were performed on the pathological specimens of patients with KOA in various low-density regions. RESULTS: The results of model validation indicated that the model was consistent with normal anatomical structures and correlated with previous calculations documented in the literature. Static analysis revealed that the maximum von Mises stress in the medial component of the normal knee was the lowest and increased with the advancement of the hypointensity zone. In contrast, the lateral component exhibited an opposing trend, with the maximum von Mises stress in the lateral component being the highest and decreasing as the hypointensity zone progressed. Additionally, the medial component experienced an increasing proportion of stress within the overall knee joint. HE staining demonstrated that the chondrocyte layer progressively deteriorated and may even disappear as the hypointensity zone expanded. Furthermore, alkaline magenta staining indicated that the severity of microfractures in the trabecular bone increased concurrently with the expansion of the hypointensity zone. CONCLUSION The presence of subtalar plateau low-density zone may aggravate joint degeneration. In clinical practice, it is necessary to pay attention to the changes in the subtalar plateau low-density zone and actively take effective measures to strengthen the bone status of the subtalar plateau low-density zone and restore the complete biomechanical function of the knee joint, in order to slow down or reverse the progression of osteoarthritis.
Humans ; Finite Element Analysis ; Knee Joint/physiology* ; Tibia/anatomy & histology* ; Cartilage, Articular/physiology* ; Menisci, Tibial/physiopathology* ; Tomography, X-Ray Computed ; Osteoarthritis, Knee/diagnostic imaging* ; Weight-Bearing ; Bone Density ; Adult ; Stress, Mechanical ; Male ; Middle Aged ; Biomechanical Phenomena ; Female

OBJECTIVES: To investigate the protective effect of Yiqi Yangyin Huazhuo Tongluo Formula (YYHT) against high glucose-induced injury in mouse renal podocytes (MPC5 cells) and the possible mechanism. METHODS: Adult Wistar rats were treated with 19, 38, and 76 g/kg YYHT or saline via gavage for 7 days to prepare YYHT-medicated or blank sera for treatment of MPC5 cells cultured in high glucose (30 mmol/L) prior to transfection with a miR-21a-5p inhibitor or a miR-21a-5p mimic. The changes in miR-21a-5p expressions and the mRNA levels of FoxO1, PINK1, and Parkin in the treated cells were detected with qRT-PCR, and the protein levels of nephrin, podocin, FoxO1, PINK1, and Parkin were detected with Western blotting. Autophagic activity in the cells were evaluated with MDC staining. The effect of miR-21a-5p mimic on FoxO1 transcription and the binding of miR-21a-5p to FoxO1 were examined with luciferase reporter gene assay and radioimmunoprecipitation assay. RESULTS: MPC5 cells exposed to high glucose showed significantly increased miR-21a-5p expression, lowered expressions of FoxO1, PINK1, and Parkin1 mRNAs, and reduced levels of FoxO1, PINK1, parkin, nephrin, and podocin proteins and autophagic activity. Treatment of the exposed cells with YYHT-medicated sera and miR-21a-5p inhibitor both significantly enhanced the protein expressions of nephrin and podocin, inhibited the expression of miR-21a-5p, increased the mRNA and protein expressions of FoxO1, PINK1 and Parkin, and upregulated autophagic activity of the cells. Transfection with miR-21a-5p mimic effectively inhibited the transcription of FoxO1 and promoted the binding of miR-21a-5p to FoxO1 in MPC5 cells, and these effects were obviously attenuated by treatment with YYHT-medicated sera. CONCLUSIONS YYHT-medicated sera alleviate high glucose-induced injury in MPC5 cells by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.
Animals ; MicroRNAs/genetics* ; Podocytes/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Autophagy/drug effects* ; Rats, Wistar ; Protein Kinases/metabolism* ; Rats ; Forkhead Box Protein O1 ; Mice ; Mitochondria/drug effects* ; Ubiquitin-Protein Ligases/metabolism* ; Glucose ; Diabetic Nephropathies ; Male ; Membrane Proteins/metabolism* ; Intracellular Signaling Peptides and Proteins

Objective:To preliminarily explore the association of pregnancy factors with cow's milk protein allergy in infants.Methods:This study was based on data from a subcohort of a study called ge-netic susceptibility to cow's milk allergy in Chinese children,including infants born in Peking University People's Hospital between March 1,2020,and December 31,2020.The infants were divided into a cow's milk protein allergy(CMPA)group and a control group according to whether they had developed cow's milk protein allergy at the age of 1 year.We retrospectively collected the clinical data of infants and their mothers before and during pregnancy,and analyzed the association of multiple factors during pregnancy with cow's milk protein allergy in infants.Results:A total of 278 infants were enrolled in this study,including 52 infants with CMPA and 226 infants without CMPA.Among them,there were 143 boys and 135 girls.The proportion of male infants in the CMPA group(69.2％)was higher than that in the control group(47.3％),and the difference was statistically significant(P=0.004).There were no significant differences in the distribution of birth weight,gestational age at birth,low-birth-weight in-fants,premature,umbilical cord entangle neck,and neonatal asphyxia between the CMPA group and the control group(P＞0.05).The proportion of mothers complicated with autoimmune diseases,anemia or antibiotics exposure during pregnancy in the CMPA group was higher than that in the control group,and there were statistical differences between the two groups(P＜0.05).There was no significant difference in the distribution of other pregnancy complications between the two groups(P＞0.05),such as eclamp-sia/preeclampsia,chronic hypertension/gestational hypertension,diabetes/gestational diabetes,thyroid diseases,and so on.There was no significant difference in the overall distribution of some blood routine indexes during pregnancy between the CMPA group and the control group(P＞0.05).Multivariate Lo-gistic regression analysis showed that male infant,mothers complicated with autoimmune diseases or ane-mia,antibiotic exposure during pregnancy were independent risk factors for cow's milk protein allergy.Conclusion:Male infant,mothers complicated with autoimmune diseases or anemia,antibiotic exposure during pregnancy were independent risk factors for cow's milk protein allergy.

The implantation of a left ventricular assist device (LVAD) is an important therapeutic tool for patients with end-stage heart failure, which can either help patients transit to the heart transplantation stage or serve as destination therapy until the end of their lives. In recent years, the third generation of LVAD has evolved rapidly and several brands have been marketed both domestically and internationally. The number of LVAD implantations has been increasing and the long-term survival rate of implanted patients has improved, so this device has a broad development perspective. This article summarizes the current status, usage standards and precautions, and common complications after implantation of LVAD, as well as looks forward to the future development of LVAD, hoping to be helpful for researchers who are new to this field.

Objective:To investigate the relationship between gestational weight gain (GWG) in twin pregnancies and adverse perinatal outcomes.Methods:This retrospective study included twin pregnant women with live births at≥25 weeks of gestation and their offspring, who delivered at Peking University People's Hospital from January 2012 to October 2022. Total GWG was standardized according to gestational age and categorized into three groups based on the 2009 Institute of Medicine (IOM) guidelines: insufficient GWG (GWG below IOM recommendations), appropriate GWG (GWG within IOM recommendations), and excessive GWG (GWG above IOM recommendations). Comparisons between data of the three groups used analysis of variance, Kruskal-Wallis test or Bonferroni correction or Chi-square partitions. Multivariable logistic regression models and generalized estimating equations with logistic regression models were used to analyze the independent effects of GWG on maternal and neonatal outcomes. Results:A total of 794 twin pregnant women and their 1 588 live-born neonates were included in the study. There were 360 women (45.3%) with appropriate GWG, 356 (44.8%) with insufficient GWG, and 78 (9.8%) with excessive GWG. Both insufficient and excessive GWG were associated with an increased risk of preterm birth [adjusted ORs of 1.39 (95% CI: 1.04-1.88) and 1.70 (95% CI: 1.05-2.78), respectively]. Insufficient GWG was associated with an increased risk of gestational diabetes mellitus (adjusted OR=1.42, 95% CI: 1.00-2.01) and low birth weight infants (adjusted OR=2.04, 95% CI: 1.57-2.66). Insufficient GWG was also associated with a reduced risk of eclampsia or preeclampsia (adjusted OR=0.50, 95% CI: 0.33-0.75), cesarean section (adjusted OR=0.48, 95% CI: 0.30-0.77), discordant twin growth (adjusted OR=0.56, 95% CI: 0.37-0.85), and large for gestational age infants (adjusted OR=0.46, 95% CI: 0.35-0.61). Excessive GWG was associated with an increased risk of eclampsia or preeclampsia (adjusted OR=2.85, 95% CI: 1.65-4.91), and large for gestational age infants (adjusted OR=2.49, 95% CI: 1.60-3.86), while with a decreased risk of low birth weight infants (adjusted OR=0.42, 95% CI: 0.27-0.65). Conclusions:More than half of the twin pregnancies have GWG outside the recommended range of the IOM guidelines. Both insufficient and excessive GWG are associated with adverse perinatal outcomes, particularly an increased risk of preterm birth.

Objective:To study the role of a novel brain-derived peptide hypoxic-ischemic brain damage associated peptide (HIBDAP) in regulating pyroptosis of oxygen-glucose deprived (OGD) microglia.Methods:The sequence of HIBDAP was coupled with the sequence of cell-penetrating peptide transactivator of transcription (TAT) to form TAT-HIBDAP. Fluorescein isothiocyanate (FITC) labeled TAT-HIBDAP was added to microglia cells and observed under fluorescence microscope. Microglia cells were treated with different concentrations of TAT-HIBDAP (1, 5, 10, 20 μmol/L) and then OGD process. Cell pyroptosis was analyzed using lactate dehydrogenase (LDH) assay. The concentration of TAT-HIBDAP with the most prominent inhibiting effects was determined and selected for subsequent experiments. The pyroptosis morphology of the control group, the OGD group and the HIBDAP group (5 μmol/L TAT-HIBDAP+OGD) was observed using transmission electron microscope. The mRNA and protein expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes were examined using real-time quantitative PCR and Western Blot analysis.Results:Fluorescence microscope showed FITC-labeled TAT-HIBDAP could successfully enter microglia cells. Compared with the OGD group, low concentrations of TAT-HIBDAP (1, 5, 10 μmol/L) could significantly reduce microglia pyroptosis and the concentration of 5 μmol/L showed the most prominent effects. Compared with the control group, OGD group showed typical pyroptosis morphology and HIBDAP group showed significantly improved morphology. The mRNA and protein expression of NLRP3 inflammasomes in the OGD group were significantly higher than the control group and also the HIBDAP group.Conclusions:The novel brain-derived peptide HIBDAP may reduce the expression of NLRP3 inflammasomes and inhibit the pyroptosis of OGD microglia.

Objective:To construct a drug knowledge base based on drug instructions.Methods:Six hundred randomly selected drug instructions were labeled manually and divided into training set and test set. The training was based on bidirectional long short-term memory(Bi-LSTM) and conditional random fields(CRF) model to complete the recognition of medical entities. The extracted entities were standardized by the hybrid model of " similarity calculation and rule mapping table" , and then the drug information was imported into the Access database.Results:In the task of named entity recognition based on Bi-LSTM and CRF model, except for the crowd entities, the other entities had achieved good results with an F-value higher than 85%. Based on the hybrid model of " similarity calculation and rule mapping table" , the accuracy of entity standardization was 88.23%.Conclusions:The effect of the machine learning model in this study is similar to that of other named entity recognition and entity standardization studies, which can complete the task of drug knowledge base construction satisfactorily.

BACKGROUND:Stem cells have been shown to not only replace damaged cells, but also secrete trophic factors, bringing a bright future for the treatment of clinical spinal cord injury.
OBJECTIVE:To review the latest advances of bone marrow mesenchymal stem cells in animal and clinical research.
METHODS:A computer-based search of Kjmed and Wanfang databases was done for relevant articles published from April 2004 to April 2014 using the keywords of“stem cells, spinal cord injuries, embryonic stem cells, neural stem cells, mesenchymal stem cells”in English and Chinese, respectively.
RESULTS AND CONCLUSION:Total y 2 745 articles were initial y retrieved, and only 50 articles were included in result analysis. Bone marrow mesenchymal stem cells have become one of the most promising sources of stem cells in the treatment of spinal cord injury. Although the bone marrow mesenchymal stem cellin the treatment of spinal cord injury is stil in its infancy, it has certain effects on the repair of spinal cord injury. The mechanism of action of bone
marrow mesenchymal stem cells in the treatment of spinal cord injury is possibly related to the substitution effect, neurotrophic effects, suppression of the immune response and promoting axonal regeneration.