To investigate the clinical characteristics and prognosis of extracranial malignant rhabdoid tumor (eMRT) in children, and to provide a reference for the clinical treatment of this disease.

Objective: To compare the effects of aerobic exercise at maximal fat oxidation (FATmax) and FATmax intensity exercise combined with resistance training (RT), and dietary restriction on the body composition, vascular endothelial function and ferroptosis in obese female university students, so as to provide a reference for exploring the mechanisms by which exercise improves vascular endothelial function. Methods: From February to May 2024, 70 obese female university students were recruited from Shanxi University and randomly divided into control group ( n =24), FATmax group ( n =24) and FATmax+RT group ( n =22). From March 4 to May 26, 2024 control group maintained their normal living habits, FATmax group performed aerobic exercise at FATmax intensity three times per week for 60 minutes per session; FATmax +RT group performed combined aerobic and resistance exercise at FATmax intensity three times per week for 60 minutes per session. The daily dietary calorie intake for all groups was determined according to resting energy expenditure. Body composition, vascular endothelial function and ferroptosis were measured before and after the intervention. Results: After 12 weeks of intervention, there were statistically significant differences in body mass, BMI, body fat, waist hip ratio and muscle mass among the three groups ( F =10.93, 5.88, 65.28, 21.14, 2.25, all P < 0.05). Compared with the control group, participants in both the FATmax group and the FATmax+RT group showed significant reductions in body weight, BMI, body fat and waist hip ratio (all P <0.05). Body fat and waist hip ratio in FATmax+RT group were lower than those in FATmax group, and muscle mass was higher than those in FATmax group and control group (both P <0.05). After 12 weeks of intervention, significant differences were observed among the three groups in serum NO, GSH, serum ferritin levels and FMD ( F = 9.14, 9.67, 4.78, 135.70, all P <0.05). Compared with the control group, the serum NO, GSH levels and FMD significantly increased, and the serum ferritin level decreased (all P <0.05) of obese female university students in FATmax group and FATmax+RT group. Serum GSH level and FMD increased and serum ferritin level decreased in FATmax +RT group when compared with FATmax group (all P <0.05). Conclusions With the same exercise training duration and frequency, FATmax intensity aerobic exercise, alone or combined with resistance and dietary restriction, can significantly improve the body composition, vascular endothelial function and inhibit ferroptosis of obese female university students. However, FATmax intensity aerobic exercise combined with resistance training has more pronounced effects.

Diterpenoid ferruginol is a key intermediate in biosynthesis of active ingredients such as tanshinone and carnosic acid.However, the traditional process of obtaining ferruginol from plants is often cumbersome and inefficient. In recent years, the increasingly developing gene editing technology has been gradually applied to the heterologous production of natural products, but the production of ferruginol in microbe is still very low, which has become an obstacle to the efficient biosynthesis of downstream chemicals, such as tanshinone. In this study, miltiradiene was produced by integrating the shortened diterpene synthase fusion protein,and the key genes in the MVA pathway were overexpressed to improve the yield of miltiradiene. Under the shake flask fermentation condition, the yield of miltiradiene reached about(113. 12±17. 4)mg·L~(-1). Subsequently, this study integrated the ferruginol synthase Sm CYP76AH1 and Sm CPR1 to reconstruct the ferruginol pathway and thereby realized the heterologous synthesis of ferruginol in Saccharomyces cerevisiae. The study selected the best ferruginol synthase(Il CYP76AH46) from different plants and optimized the expression of pathway genes through redox partner engineering to increase the yield of ferruginol. By increasing the copy number of diterpene synthase, CYP450, and CPR, the yield of ferruginol reached(370. 39± 21. 65) mg·L~(-1) in the shake flask, which was increased by 21. 57-fold compared with that when the initial ferruginol strain JMLT05 was used. Finally, 1 083. 51 mg·L~(-1) ferruginol was obtained by fed-batch fermentation, which is the highest yield of ferruginol from biosynthesis so far. This study provides not only research ideas for other metabolic engineering but also a platform for the construction of cell factories for downstream products.
Saccharomyces cerevisiae/genetics* ; Diterpenes/metabolism* ; Metabolic Engineering ; Fermentation ; Abietanes

This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Plant Leaves/chemistry*

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

Ferroptosis has received great attention as an iron-dependent programmed cell death for efficient cancer therapy. However, with the accumulation of iron in tumor cells, the antioxidant system is activated by reducing glutathione (GSH) with glutathione peroxidase 4 (GPX4), which critically limits the ferroptosis therapeutic effect. Herein, an iron and GPX4 silencing siRNA (siGPX4) co-encapsulated ferritin nanocage (HFn@Fe/siGPX4) was developed to enhance ferroptosis by disruption of redox homeostasis and inhibition of antioxidant enzyme synergistically. The siGPX4 were loaded into the nanocages by pre-incubated with iron, which could significantly improve the loading efficiency of the gene drugs when compared with the reported gene drug loading strategy by ferritin nanocages. And more iron was overloaded into the ferritin through the diffusion method. When HFn@Fe/siGPX4 was taken up by human breast cancer cell MCF-7 in a TfR1-mediated pathway, the excess iron ions in the drug delivery system could for one thing induce ferroptosis by the production of reactive oxygen species (ROS), for another promote siGPX4 escaping from the lysosome to exert gene silencing effect more effectively. Both the in vitro and in vivo results demonstrated that HFn@Fe/siGPX4 could significantly inhibit tumor growth by synergistical ferroptosis. Thus, the developed HFn@Fe/siGPX4 afforded a combined ferroptosis strategy for ferroptosis-based antitumor as well as a novel and efficient gene drug delivery system.

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

Early-life stress (ES) leads to cognitive dysfunction in female adolescents, but the underlying neural mechanisms remain elusive. Recent evidence suggests that the cell adhesion molecules NECTIN1 and NECTIN3 play a role in cognition and ES-related cognitive deficits in male rodents. In this study, we aimed to investigate whether and how nectins contribute to ES-induced cognitive dysfunction in female adolescents. Applying the well-established limited bedding and nesting material paradigm, we found that ES impairs recognition memory, suppresses prefrontal NECTIN1 and hippocampal NECTIN3 expression, and upregulates corticotropin-releasing hormone (Crh) and its receptor 1 (Crhr1) mRNA levels in the hippocampus of adolescent female mice. Genetic experiments revealed that the reduction of dorsal CA1 (dCA1) NECTIN3 mediates ES-induced object recognition memory deficits, as knocking down dCA1 NECTIN3 impaired animals' performance in the novel object recognition task, while overexpression of dCA1 NECTIN3 successfully reversed the ES-induced deficits. Notably, prefrontal NECTIN1 knockdown did not result in significant cognitive impairments. Furthermore, acute systemic administration of antalarmin, a CRHR1 antagonist, upregulated hippocampal NECTIN3 levels and rescued object and spatial memory deficits in stressed mice. Our findings underscore the critical role of dCA1 NECTIN3 in mediating ES-induced object recognition memory deficits in adolescent female mice, highlighting it as a potential therapeutic target for stress-related psychiatric disorders in women.
Animals ; Female ; Mice ; CA1 Region, Hippocampal/metabolism* ; Cell Adhesion Molecules/metabolism* ; CRF Receptor, Type 1/metabolism* ; Memory Disorders/etiology* ; Mice, Inbred C57BL ; Nectins/genetics* ; Receptors, Corticotropin-Releasing Hormone/antagonists & inhibitors* ; Recognition, Psychology/physiology* ; Stress, Psychological/complications*

Objective:To compare the efficacy of O-arm navigation-assisted and freehand posterior pedicle screw fixation in the treatment of ankylosing spondylitis (AS) associated with lower cervical fractures in adults.Methods:A retrospective cohort study was conducted to analyze the clinical data of 29 adult AS patients with lower cervical fractures admitted to Zhengzhou Orthopedic Hospital from June 2020 to September 2024, including 22 males and 7 females, aged 35-72 years [(52.3±11.1)years]. Injured segments involved C 5~6 in 6 patients, C 6 in 8, C 6~7 in 8, and C 7 in 7. Accirdubg to AO classification, the fracture was classified as type B3 in 22 patients and type C in 7. All the patients underwent posterior cervical pedicle screw fixation, among whom 15 patients were treated with navigation-assisted screw placement (navigation screw placement group, with 120 screws) and 14 with freehand technique (freehand screw placement group, with 112 screws). The two groups were compared in terms of the operative time, intraoperative blood loss, and postoperative drainage volume. The accuracy of screw placement, penetration rate of the pedicle cortex and fracture healing time were evaluated in the two groups. The Cobb angle before surgery and at 3 days after surgery and American Spinal Injury Association (ASIA) classification before surgery and at the last follow-up were recorded in the two groups. The visual analogue scale (VAS) score, Japanese Orthopedic Association (JOA) score and neck dysfunction index (NDI) before surgery, at 1 week, 3 months after surgery and at the last follow-up were compared between the two groups. The incidence of postoperative complications was also investigated. Results:All the patients were followed up for 6-57 months [(29.3±14.1)months]. The operation duration, intraoperative blood loss, and postoperative drainage volume were (166.0±31.4)minutes, (256.7±70.7)ml, and (91.0±14.4)ml in the navigation screw placement group, which were shorter or less than (219.29±31.7)minutes, (342.1±60.7)ml, and (123.2±20.7)ml in the freehand screw placement group ( P<0.01). The accuracy of screw placement in the navigation screw placement group was 98.3% (118/120) and penetration rate of the pedicle cortex was 5.8% (7/120), which were both superior to 89.3% (100/112) and 18.8% (21/112) in the freehand screw placement group ( P<0.01). No significant difference was detected in fracture healing time between the two groups ( P>0.05). There were no significant differences in the Cobb angle before surgery and at 3 days after surgery, as well as in the ASIA grading before surgery and at the last follow-up between the two groups ( P>0.05). The Cobb angle and ASIA classification at 3 days after surgery and at the last follow-up were improved compared with those before surgery ( P<0.05). Before surgery, at 1 week, 3 months after surgery, and at the last follow-up, the VAS scores were 8.0(7.0, 9.0)points, 4.0(3.0, 4.0)points, 2.0(1.0, 2.0)points, and 0.0(0.0, 1.0)points in the navigation screw placement group, which were not significantly different from 8.0(7.0, 9.0)points, 4.0(3.0, 4.0)points, 1.5(1.0, 2.0)points, and 0.0(0.0, 1.0)points in the freehand screw placement group ( P>0.05); the JOA scores were (7.5±1.4)points, (10.9±1.2)points, (13.2±1.5)points, and (15.7±1.0)points in the navigation screw placement group, which were not significantly different from (7.2±2.8)points, (10.1±3.2)points, (11.8±3.8)points, and (14.1±4.3)points in the freehand screw placement group ( P>0.05); the NDI were 48.0(44.0, 56.0)%, 30.0(30.0, 34.0)%, 18.0(16.0, 22.0)%, 8.0(6.0, 10.0)% in the navigation screw placement group, which were not significantly different from 44.0(40.0, 52.0)%, 30.0(29.0, 34.5)%, 17.0(16.0, 20.0)%, and 8.0(5.5, 10.0)% in the freehand screw placement group ( P>0.05). The VAS scores, JOA scores, and NDI were improved at 1 week, 3 months after surgery, and at the last follow-up in both groups, compared to those before surgery and they were gradually improved with the passage of the follow-up time ( P<0.05). One patient in the navigation screw placement group developed postoperative pulmonary infection and recovered after symptomatic treatment, with an incidence of complications 7% (1/15). Two patients in the freehand screw placement group had postoperative cerebrospinal fluid leakage and dural rupture and recovered after symptomatic treatment, with an incidence of complications 14% (2/14). Throughout the follow-up period, no complications such as screw breakage, implant loosening, or loss of correction were found in either group. Conclusion:Compared with freehand screw placement, the O-arm navigation system-assisted posterior pedicle screw fixation in the treatment of AS associated with lower cervical fractures in adults demonstrates significant advantages, including reduced operative time, decreased intraoperative blood loss and postoperative drainage volume, improved accuracy of screw placement, and reduced penetration rate of the pedicle cortex.

Objective:To compare the efficacy of whole-process visualization system-assisted pedicle screw internal fixation and free-hand pedicle screw internal fixation in the treatment of thoracolumbar burst fracture (TLBF) without neurologic symptoms.Methods:A retrospective cohort study was conducted to analyze the clinical data of 64 patients with TLBF without neurologic symptoms admitted to Zhengzhou Orthopedic Hospital from December 2020 to October 2022, including 41 males and 23 females, aged 23-52 years [(42.1±6.6)years]. The injured vertebrae involved T 11 in 26 patients, T 12 in 17, L 1 in 12, and L 2 in 9. The Wiltse approach was used in all the patients, 31 of whom were treated with pedicle screw internal fixation assisted by the whole-process visualization system (visualization system-assisted screw placement group) and 33 of whom were treated with free-hand pedicle screw internal fixation (free-hand screw placement group). The two groups were compared in terms of operation time, single screw placement time, intraoperative blood loss, intraoperative total radiation dose and total length of hospital stay. The accuracy of pedicle screw placement and penetration rate of the pedicle cortex were evaluated in the two groups. The Cobb angle and lumbar visual analogue scale (VAS) before surgery, at 1 week, 3 months after surgery and at the last follow-up were compared between the two groups. The incidence of postoperative complications was also investigated. Results:All the patients were followed up for 10-33 months [(17.5±4.8)months]. The operation time was (106.9±11.8)minutes in the visualization system-assisted screw placement group, shorter than (121.3±11.4)minutes in the free-hand screw placement group ( P<0.01). The single screw placement time was (9.1±1.0)minutes in the visualization system-assisted screw placement group, shorter than (11.7±1.5)minutes in the free-hand screw placement group ( P<0.01). The total radiation dose was (10.4±2.4)mGy in the visualization system-assisted screw placement group, lower than (51.8±7.2)mGy in the screw placement group ( P<0.01). There was no significant difference in intraoperative blood loss or total length of hospital stay between the two groups ( P>0.05). The accuracy of pedicle screw placement was 96.6% (197/204) in the visualization system-assisted screw placement group, significantly higher than 89.3% (191/214) in the free-hand screw placement group ( P<0.01). Both groups showed significant improvements in Cobb angle and VAS scores at 1 week, 3 months after surgery, and at the last follow-up ( P<0.05). There were no significant differences in Cobb angle or VAS scores between the two groups at each time point ( P>0.05). In the visualization system-assisted screw placement group, one patient had incision infection at 4 days after operation, which was cured with antibiotics. One patient in the free-hand screw placement group developed the symptoms of nerve root irritation at 2 days after surgery, which disappeared at 7 days after revision. There was no significant difference in the incidence of complications between the two groups ( P>0.05). During the follow-up, no patients had broken screws, loosening of internal fixation, or loss of correction in either group. Conclusions:Compared with free-hand pedicle screw internal fixation, the whole-process visualization system-assisted pedicle screw internal fixation in the treatment of TLBF without neurologic symptoms can shorten the time of operation and screw placement, reduce the radiation dose, and improve the accuracy of pedicle screw placement, suggesting that it is a safer and more effective auxiliary method for pedicle screw placement.