Objective:This study aimed to investigate the role of bone morphogenetic protein 2 (BMP2)/Smad8 signaling pathway in T-2 toxin-induced apoptosis of rat articular chondrocytes.Methods:Primary chondrocytes from SD rats were cultured in vitro and exposed to varying concentrations of T-2 toxin (0.00, 0.32, 1.60, 8.00 ng/ml). The changes in chondrocytes survival rate were determined by CCK8, and the apoptosis changes of chondrocytes were determined by TUNEL assay kit. Using a group design, chondrocytes were cultured in complete culture media and culture media containing T-2 toxin (1.60 ng/ml), BMP2 cytokine (500 ng/ml), or T-2 toxin (1.60 ng/ml) + BMP2 cytokine (500 ng/ml), referred to as the control group, T-2 toxin group, BMP2 group, and T-2 toxin + BMP2 group, respectively. The survival rate and apoptosis changes of chondrocytes in each group were determined. The expression levels of Caspase-3, BMP2, BMP receptor Ⅱ (BMP-R Ⅱ), and Smad1/4/5/8 were determined by quantitative real-time PCR. Results:Compared with the 0.00 ng/ml of T-2 toxin group [(100.00 ± 0.00)%, (4.33 ± 0.32)%], the chondrocyte survival rates [(85.77 ± 2.96)%, (72.79 ± 2.31)%, (48.87 ± 1.83)%] of the 0.32, 1.60, and 8.00 ng/ml of T-2 toxin groups were significantly lower ( P < 0.05), and the apoptosis rates [(5.43 ± 0.32)%, (6.17 ± 0.15)%, (5.07 ± 0.13)%] were significantly higher ( P < 0.05). Compared with the control group, the T-2 toxin group had a lower survival rate and a higher apoptosis rate of chondrocytes ( P < 0.05). Compared with the T-2 toxin group, the T-2 toxin + BMP2 group had a higher survival rate and lower apoptosis rate of chondrocytes ( P < 0.05). Compared with the control group, the T-2 toxin group showed higher expression level of Caspase-3 mRNA in chondrocytes, while the expression levels of BMP2, BMP-R Ⅱ, and Smad1/4/8 mRNA were lower ( P < 0.05). Compared with the T-2 toxin group, the expression level of Caspase-3 mRNA was lower in the T-2 toxin + BMP2 group, while the expression levels of BMP2 and Smad8 mRNA were higher ( P < 0.05). Conclusion:BMP2 may partially block the apoptosis of chondrocytes caused by T-2 toxin by regulating the BMP2/Smad8 signaling pathway.

The wrist joint is a highly mobile functional joint. Wrist conditions including traumatic and degenerative arthritis, rheumatoid arthritis, and giant cell tumors of the distal radius, cause significant pain and mobility impairment. In joint surgery, the decision to use joint prostheses to reconstruct joint function is greatly influenced by the characteristics of the prosthesis (Mok et al., 2016). However, traditional implants have limitations such as shape mismatch, inadequate implant-bone interface strength which causes loosening, and poor bone ingrowth (Zhang et al., 2014).
Humans ; Joint Prosthesis ; Wrist Joint/surgery* ; Prosthesis Design ; Arthroplasty, Replacement ; Arthritis, Rheumatoid/surgery*

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective:This study aimed to investigate the role of bone morphogenetic protein 2 (BMP2)/Smad8 signaling pathway in T-2 toxin-induced apoptosis of rat articular chondrocytes.Methods:Primary chondrocytes from SD rats were cultured in vitro and exposed to varying concentrations of T-2 toxin (0.00, 0.32, 1.60, 8.00 ng/ml). The changes in chondrocytes survival rate were determined by CCK8, and the apoptosis changes of chondrocytes were determined by TUNEL assay kit. Using a group design, chondrocytes were cultured in complete culture media and culture media containing T-2 toxin (1.60 ng/ml), BMP2 cytokine (500 ng/ml), or T-2 toxin (1.60 ng/ml) + BMP2 cytokine (500 ng/ml), referred to as the control group, T-2 toxin group, BMP2 group, and T-2 toxin + BMP2 group, respectively. The survival rate and apoptosis changes of chondrocytes in each group were determined. The expression levels of Caspase-3, BMP2, BMP receptor Ⅱ (BMP-R Ⅱ), and Smad1/4/5/8 were determined by quantitative real-time PCR. Results:Compared with the 0.00 ng/ml of T-2 toxin group [(100.00 ± 0.00)%, (4.33 ± 0.32)%], the chondrocyte survival rates [(85.77 ± 2.96)%, (72.79 ± 2.31)%, (48.87 ± 1.83)%] of the 0.32, 1.60, and 8.00 ng/ml of T-2 toxin groups were significantly lower ( P < 0.05), and the apoptosis rates [(5.43 ± 0.32)%, (6.17 ± 0.15)%, (5.07 ± 0.13)%] were significantly higher ( P < 0.05). Compared with the control group, the T-2 toxin group had a lower survival rate and a higher apoptosis rate of chondrocytes ( P < 0.05). Compared with the T-2 toxin group, the T-2 toxin + BMP2 group had a higher survival rate and lower apoptosis rate of chondrocytes ( P < 0.05). Compared with the control group, the T-2 toxin group showed higher expression level of Caspase-3 mRNA in chondrocytes, while the expression levels of BMP2, BMP-R Ⅱ, and Smad1/4/8 mRNA were lower ( P < 0.05). Compared with the T-2 toxin group, the expression level of Caspase-3 mRNA was lower in the T-2 toxin + BMP2 group, while the expression levels of BMP2 and Smad8 mRNA were higher ( P < 0.05). Conclusion:BMP2 may partially block the apoptosis of chondrocytes caused by T-2 toxin by regulating the BMP2/Smad8 signaling pathway.

Bone grafting is a primary method for treating bone defects. Among various graft materials, xenogeneic bone substitutes are widely used in clinical practice due to their abundant sources, convenient processing and storage, and avoidance of secondary surgeries. With the advancement of domestic production and the limitations of imported products, an increasing number of bone filling or grafting substitute materials isentering clinical trials. Relevant experts have drafted this consensus to enhance the management of medical device clinical trials, protect the rights of participants, and ensure the scientific and effective execution of trials. It summarizes clinical experience in aspects, such as design principles, participant inclusion/exclusion criteria, observation periods, efficacy evaluation metrics, safety assessment indicators, and quality control, to provide guidance for professionals in the field.
Humans ; Bone Substitutes/therapeutic use* ; Randomized Controlled Trials as Topic/methods* ; Consensus ; Bone Transplantation ; Research Design

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

BACKGROUND: Stress cardiomyopathy (SCM) currently has a high incidence in older adults, and the theories regarding its causes include "catecholamine myocardial toxicity" and "sympathetic hyperactivation". However, the role of the central nervous system in the pathogenesis of SCM remains unknown. We investigated the role of microglia activation in the paraventricular hypothalamic nucleus (PVN) in the development of SCM. METHODS: An SCM model was created using male Sprague-Dawley (SD) rats, immobilized for 6 h every day for a week. Electrocardiogram, cardiac electrophysiology, and echocardiography examinations were performed to verify the changes in cardiac structure and function in rats with SCM. RNA sequencing was used to explore the changes in the hypothalamus during SCM. In addition, brain and heart tissues were collected to detect microglial activation and sympathetic activity. RESULTS: The main findings were as follows: (1) immobilization stress successfully induced SCM in SD rats; (2) microglia were significantly activated in the hypothalamus, as evidenced by cytosol thickening, increases in the number of microglial branches, and microglia enriched in the PVN; (3) in SCM, the microglia in the PVN exhibited increased central and peripheral cardiac sympathetic activity and increased the expression of neuroinflammatory factors; and (4) it is possible that inhibiting microglial activation could suppress the sympathetic activity of the central nervous system and heart and increase cardiac electrical stability in SCM rats. CONCLUSIONS SCM was induced in SD rats by immobilization stress, acting through the activation of the hypothalamic microglia. The activated microglia were specifically enriched in the PVN, increasing the activity of the central and peripheral sympathetic nervous systems by regulating the expression of neuro-inflammatory factors, mediating dysfunction of the left ventricle, and increasing the susceptibility to ventricular arrhythmias.

Objective : To explore the differences in the effects of psoriatic serum and a mixture of five proinflam⁃ matory cytokines on keratinocyte inflammation and proliferation . Methods : he human immortalized keratinocyte cell line (HaCaT cells) was used to cultivate with serum of healthy human serum , psoriasis patients and M5 factors , and the cell proliferation was monitored by CCK⁃8 . RT⁃qPCR was used to detect the mRNA expression levels of inflammatory factors interleukin 1β/8/21 /23 (IL⁃1β/8/21 /23) , proliferation markers keratin 6/16 (K6/K16) and nucleus related antigen 67 (Ki67) in HaCaT cells in each group . Results : Healthy human serum , psoriasis serum and M5 factors could effectively promote the growth of HaCaT cells , and psoriasis serum and M5 factors could promote cell growth more than healthy human serum . Similar to M5 factors , serum from patients with psoriasis significantly promoted the mRNA levels of inflammatory factors IL⁃1β , IL⁃8 , IL⁃23 and proliferation markers K6 and Ki67 in cells . Different from M5 factors , the serum of psoriasis patients had enhanced the mRNA level of inflammatory factor IL⁃21 , but weakened the promotion of proliferation marker K16 . Conclusion The serum micro environment of patients with psoriasis can promote the proliferation and inflammatory response of keratinocytes higher than that of healthy people , and is similar to M5 factors , which can be used to build a keratinocyte model of psoriasis .

Humans ; Spinal Cord Injuries/complications* ; Paralysis/etiology* ; Nervous System Diseases ; Brain

With the development of medicine technology and the increasing of people’s demand for quality of life, the complexity of doctor-patient relationships is also increasing. Pediatrics is one of the departments with the most concentrated and complex doctor-patient conflicts, therefore, it is necessary to analyze the sick roles and doctor-patient relationships in pediatrics. This paper explained the connotation of the sick role and the doctor-patient social interaction pattern based on Parsons’ theory of "sick role", and analyzed the particularity of the pediatric sick roles in China according to China’s national conditions. Meanwhile, combining the group characteristics and social background of pediatric sick role, this paper elaborated the sociological crux of pediatric doctor-patient relationship in China, and conducted a critical analysis on Parsons’ theory of "sick role".