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

OBJECTIVE: To observe the clinical symptoms and MRI outcomes of patients with ruptured lumbar disc herniation(LDH) through a multicenter randomized controlled study, and to evaluate the clinical efficacy and safety of Yiqi Huoxue formula() in the treatment of this disease. METHODS: A total of 160 outpatients and inpatients with ruptured LDH admitted to 4 medical centers from January 2023 to June 2023 were selected and randomly divided into the Yiqi Huoxue formula group and the control group, with 80 patients in each group. In the Yiqi Huoxue formula group, there were 43 males and 37 females, with an age of (41.03±9.56) years and a disease duration of (10.45±25.37) days, and the patients were treated with Yiqi Huoxue formula. In the control group, there were 34 males and 46 females, with an age of (42.14±8.73) years and a disease duration of (11.31±21.14) days;during the acute phase, patients in this group could take celecoxib capsules orally, and methylcobalamin orally at the same time. The Japanese Orthopaedic Association (JOA) score, Oswestry disability index (ODI), changes in the volume of herniated disc tissue on MRI, herniation rate, and absorption rate were recorded at the time of enrollment and during follow-ups at the 3rd, 6th, and 12th month after treatment. RESULTS: A total of 156 patients completed the clinical follow-up, and 4 patients withdrew midway. The clinical symptoms of all patients who completed the study were relieved to varying degrees, and reabsorption of herniated disc tissue was observed in all patients in the Yiqi Huoxue formula group after treatment. For the JOA score:in the Yiqi Huoxue formula group, it was (10.73±2.76) points before treatment and (24.65±2.19) points at the 12th month after treatment;in the control group, it was (11.01±1.20) points before treatment and (17.07±3.26) points at the 12th month after treatment. For the ODI score:in the Yiqi Huoxue formula group, it was (26.21±3.55) points before treatment and (5.65±2.19) points at the 12th month after treatment;in the control group, it was (27.92±2.51) points before treatment and (9.09±2.15) points at the 12th month after treatment. At the 12th month after treatment, the JOA and ODI scores of both groups were better than those before treatment, and the scores of the Yiqi Huoxue formula group were better than those of the control group, with statistically significant differences (P<0.05). In terms of the herniated disc volume and herniation rate on MRI, the Yiqi Huoxue formula group was superior to the control group, with statistically significant differences(P<0.05). Reabsorption occurred in 56.96%(45/79) of patients in the Yiqi Huoxue formula group, which was significantly higher than the 37.66%(29/77) in the control group. CONCLUSION After treatment with Yiqi Huoxue formula, patients with ruptured LDH show significant improvement in clinical symptoms and a marked reduction in the volume of herniated discs. During the follow-up period, no obvious adverse drug reactions are observed in patients, and no recurrence of symptoms is found at the last follow-up, indicating that the formula has safe and reliable efficacy.
Humans ; Male ; Female ; Intervertebral Disc Displacement/drug therapy* ; Adult ; Drugs, Chinese Herbal/adverse effects* ; Middle Aged ; Lumbar Vertebrae

OBJECTIVE: To investigate the genetic causal relationship of leukocyte telomere length (LTL) with prostatitis, orchitis and epididymitis by two-sample Mendelian randomization (MR). METHODS: Using LTL as the exposure factor and prostatitis, orchitis and epididymitis as outcome factors, we mined the Database of Genome-Wide Association Studies (GWAS). Then, we analyzed the causal relationship of LTL with prostatitis, orchitis and epididymitis by Mendelian randomization using inverse variance weighting (IVW) as the main method and weighted median and MR-Egger regression as auxiliary methods, determined the horizontal multiplicity by MR-Egger intercept test, and conducted sensitivity analysis using the leaving-one-out method. RESULTS: A total of 121 related single nucleotide polymorphisms (SNPs) were identified in this study. IVW showed LTL to be a risk factor for prostatitis (OR = 1.383, 95% CI: 1.044－1.832, P = 0.024), and for orchitis and epididymitis as well (OR = 1.770, 95% CI: 1.275－2.456, P = 0.000 6). CONCLUSION Genetic evidence from Mendelian randomized analysis indicates that shortening of LTL reduces the risk of prostatitis, orchitis and epididymitis.
Humans ; Male ; Mendelian Randomization Analysis ; Epididymitis/genetics* ; Prostatitis/genetics* ; Polymorphism, Single Nucleotide ; Leukocytes ; Orchitis/genetics* ; Genome-Wide Association Study ; Telomere ; Risk Factors

Probiotics play a crucial role in colon cancer treatment by metabolizing prebiotics to generate short-chain fatty acids (SCFAs). Colon cancer patients are frequently propositioned to supplement with probiotics to enhance the conversion and utilization of prebiotics. Nevertheless, the delivery and colonization of probiotics is hindered by the harsh conditions of gastrointestinal tract (GIT). Here, we devised a straightforward yet potent modified prebiotic-based "shield" (Gelatin-Inulin, GI), employing dietary inulin and natural polymer gelatin crosslinked via hydrogen bonding for enveloping Lactobacillus reuteri (Lr) to formulate synbiotic hydrogel capsules (Lr@Gl). The GI "shield" serves as a dynamic barrier, augmenting the resistance of Lr to gastric acid and facilitating its bioactivity and adherence in the GIT, synergizing with Lr to elicit an anti-tumor effect. Simultaneously, Lr@GI demonstrates anti-tumor effects by depleting glutathione to release reactive oxygen species, accompanied by the activation of NLRP3 (NOD-like receptor family pyrin domain containing 3), and the induction M1 macrophage polarization. Furthermore, Lr@GI can not only promote the recovery of intestinal barrier but also regulate intestinal flora, promoting the production of SCFAs and further exerting anti-tumor effect. Crucially, Lr@GI also potentiates the anti-tumor effect of 5-Fluorouracil. The construction and synergistic anti-tumor mechanism of synbiotic hydrogel capsules system provide valuable insights for gut microbial tumor therapy.

OBJECTIVE To investigate the effects and mechanism of Yiqi huoxue decoction （YQHX） on lumbar disc herniation in rats. METHODS Rats were randomly divided into sham operation group， model group， NF-κB inhibitor group （QNZ group， 1 mg/kg）， YQHX group （9.1 g/kg） and combination group （YQHX+QNZ group， the same dose as each single drug group）， with 10 rats in each group. Except for sham operation group， lumbar disc herniation model of rats was induced in other groups； administration groups were given QNZ intraperitoneally or/and YQHX intragastrically， once a day， for 8 consecutive weeks. The severity of intervertebral disc herniation was evaluated in each group； the pathological changes of intervertebral discs and the changes of autophagy of nucleus pulposus cells were all observed； the level of tumor necrosis factor-α （TNF-α） in serum， and the ratios of Bcl-2/adenovirus E1B interacting protein 3 （BNIP3） and Beclin-1 positive cells in intervertebral disctissues were detected； the phosphorylation of nuclear factor-κB （NF-κB） p65， the expressions of tumor necrosis factor receptor- associated factor-2 （TRAF-2）， TRAF-3， BNIP3 and LC3B protein， and mRNA expressions of NF-κB p65， LC3B， p62，BNIP3 and Beclin-1 were determined. RESULTS Compared with model group， Pfirrmann grading score decreased significantly，the pathological injury of intervertebral disc tissue was relieved in YQHX group； the number of autophagosomes in nucleus pulposus cells increased； serum level of TNF-α and mRNA expression of p62 in intervertebral disc tissue decreased significantly； the ratios of BNIP3 and Beclin-1 positive cells， the phosphorylation of NF-κB p65， the expressions of TRAF-2， TRAF-3， BNIP3 and LC3B protein as well as the mRNA expressions of NF- κB p65， LC3B， BNIP3 and Beclin-1 decreased significantly in intervertebral disc tissues （P＜0.05）. The changes of above indexes in YQHX group were reversed partly in YQHX+QNZ group. CONCLUSIONS YQHX promotes the elevation of autophagy level of intervertebral discs， slows down the inflammatory response and the progression of lumbar disc herniation by activating the NF-κB signaling pathway.

Hemophilic arthritis(HA),caused by recurrent bleeding,can seriously affect patient quality of life and consumes extensive social and medical resources.There is thus a need to establish an animal model of HA for research;however,this is limited by ethical requirements.Here we review the recent literature and summarize research progress into animal models of HA at home and abroad,from the aspects of species selection,modeling method,histopathology,and imaging evaluation method.Species selection includes rodents such as mice,New Zealand rabbits,beagles,miniature pigs,and crab-eating macaques.Modeling method comprise gene knockout trauma models,gene knockout spontaneous models,and injection models.Among these,the gene knockout spontaneous model closely mimics the pathological process of spontaneous bleeding and concurrent arthritis in human HA,making it more relevant to human HA.However,due to high modeling costs,phenotypic instability,and low survival rates,this model is not the preferred choice for animal experimental studies.In contrast,gene knockout trauma models exhibit characteristics such as short modeling time,strong stability,and high success rates,thus being widely utilized in animal experimental research.Evaluation of HA models involves various imaging method including MRI,micro-CT,MSKUS/PD,in addition to various gross scoring method.By reviewing the progress of HA model research,more experimental evidence is provided for investigating the pathogenesis and validating the efficacy of HA treatments,thereby compensating for the lack of clinical data,particularly in the field of traditional Chinese medicine therapy.

Objective To investigate the nutritional status of children with cystic fibrosis(CF)and understand the correlation between malnutrition and clinical characteristics as well as lung function.Methods A retrospective analysis was performed on clinical data of CF children admitted from January 2016 to June 2023.Clinical characteristics of CF children with different nutritional statuses were compared,and the correlation between malnutrition and lung function was analyzed.Results A total of 52 CF children were included,comprising 25 boys(48％)and 27 girls(52％),aged between 7 months and 17 years.Respiratory symptoms were the predominant clinical manifestations(96％,50/52).The prevalence of malnutrition was 65％(34/52),with moderate/severe malnutrition being the most common(65％,22/34).The malnutrition group had a longer duration of illness,higher proportion of digestive system symptoms,and lower levels of serum albumin(P＜0.05).Pulmonary function parameters,including forced expiratory volume in one second as a percentage of the predicted value,ratio of forced expiratory volume in one second to forced vital capacity,forced expiratory flow at 25％of forced vital capacity exhaled,forced expiratory flow at 50％of forced vital capacity exhaled,forced expiratory flow at 75％of forced vital capacity exhaled,and maximum mid-expiratory flow as a percentage of the predicted value,were lower in the malnutrition group compared to the normal nutrition group(P＜0.05).Correlation analysis showed body mass index Z-score was positively correlated with the above six pulmonary function parameters(P＜0.05).Conclusions The prevalence of malnutrition is high in CF children and is associated with decreased lung function.CF children with higher body mass index have better lung function.Therefore,screening and evaluation of nutritional status as well as appropriate nutritional intervention should be emphasized in CF children.[Chinese Journal of Contemporary Pediatrics,2024,26(3):275-281]

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

"Shaoyang as the pivot"is one of the important concepts in the theory of traditional Chinese medicine.It is believed that shaoyang is located between half exterior and half interior,which reaches the muscular striae and the exterior and connects with the internal organs,and plays the role of promoting qi movement,regulating water channel and distributing ministerial fire.The dysfunction of shaoyang pivot leads to the disorder of qi movement,abnormal water metabolism,and stagnation or hyperactivity of ministerial fire.Cholinergic urticaria is a special type of urticaria caused by the disorder of cholinergic nerve conduction,which has a long course of disease and is difficult to be cured.According to the clinical characteristics of the disease,Professor SUI Dao-Shun believes that the dysfunction of shaoyang pivot is the core pathogenesis of cholinergic urticaria.Emotional disorders lead to the dysfunction of pivot,and then cause the disordered flow of qi and fluid and internal disturbance of hyperactive ministerial fire,which induce the disharmony between nutritive qi and defensive qi,and the failure of being against the pathogens.Finally,wind pathogen attacks the skin and muscular striae and becomes latent,and results in cholinergic urticaria.For the treatment of cholinergic urticaria,Chaihu Guizhi Decoction can be used as the basic prescription to harmonize shaoyang,expel pathogens and release exterior.Corresponding modification of herbal medicines should be performed for various syndromes caused by the dysfunction of shaoyang pivot such as qi stagnation,dampness retention and heat stagnation during the clinical application.The prevention and treatment of cholinergic urticaria based on the theory of shaoyang as the pivot can provide thoughts for the clinical treatment of cholinergic urticaria.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.