OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Chronic visceral pain is a persistent and debilitating condition arising from dysfunction or sensitization of the visceral organs and their associated nervous pathways. Increasing evidence suggests that imbalances in central nervous system function play an essential role in the progression of visceral pain, but the exact mechanisms underlying the neural circuitry and molecular targets remain largely unexplored. In the present study, the ventral tegmental area (VTA) was shown to mediate visceral pain in mice. Visceral pain stimulation increased c-Fos expression and Ca²⁺ activity of glutamatergic VTA neurons, and optogenetic modulation of glutamatergic VTA neurons altered visceral pain. In particular, the upregulation of NMDA receptor 2A (NR2A) subunits within the VTA resulted in visceral pain in mice. Administration of a selective NR2A inhibitor decreased the number of visceral pain-induced c-Fos positive neurons and attenuated visceral pain. Pharmacology combined with chemogenetics further demonstrated that glutamatergic VTA neurons regulated visceral pain behaviors based on NR2A. In summary, our findings demonstrated that the upregulation of NR2A in glutamatergic VTA neurons plays a critical role in visceral pain. These insights provide a foundation for further comprehension of the neural circuits and molecular targets involved in chronic visceral pain and may pave the way for targeted therapies in chronic visceral pain.
Animals ; Male ; Visceral Pain/metabolism* ; Up-Regulation/physiology* ; Ventral Tegmental Area/metabolism* ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; Neurons/drug effects* ; Mice, Inbred C57BL ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Chronic Pain/metabolism* ; Glutamic Acid/metabolism*

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Objective To investigate the imaging features of Langerhans cell histiocytosis(LCH)in the long bones of the limbs in children.Methods The clinical and imaging data of 23 children with long bones of the limbs were analyzed retrospectively.X-ray examinations were performed in 21 cases,CT scans in 16 cases,and MRI scans in 19 cases.Results The lesions were located in femur in 14 cases,tibia in 3 cases,fibula in 2 cases,humerus in 1 case,ulna in 2 cases,and both tibia and fibula in 1 case.Lesions were found in the diaphysis in 16 cases and the metaphysis in 7 cases(involving the epiphysis in 2 cases).Bone destruction appeared as oval,irregular,or eccentric shapes,with clear boundaries in 17 cases,blurred boundaries in 6 cases,and sclerosis in 6 cases.The average CT value was(48.27±8.20)HU,with"gear-like"changes in the axial view in 10 cases."Sleeve-like"periosteal reaction was observed in 14 cases,localized periosteal reaction in 5 cases,and no periosteal reaction in 4 cases.The lesions showed iso-or slightly hypointense signals on T1 WI,hyperintense signals on T2 WI,and hyperintense signals on diffusion weighted imaging(DWI),with an average apparent diffusion coefficient(ADC)value of(1.26±0.17)×10-3 mm2/s.Soft tissue masses were found in 7 cases.After enhancement,moderate to marked enhancement was observed in 9 cases,with lace-like enhancement in 6 cases.Among the 17 cases followed up,13 cases returned to normal or had only residual bone cortical thickening,3 cases showed a reduction in lesion size,and 1 case died.Conclusion The imaging features of LCH in the long bones in children have certain characteristics,but can still be easily confused with infections or malignant bone tumors.A comprehensive analysis combining clinical and imaging features is necessary to improve diagnostic accuracy.

Objective:To explore the expressions and significance of nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3), cysteinyl aspartate specific proteinase-1 (Caspase-1) and interleukin-1β (IL-1β) in patients with hemorrhagic stroke.Methods:One hundred and three patients with hemorrhagic stroke who visited the Department of Neurosurgery of the Second Affiliated Hospital of Zhengzhou University from January 2022 to January 2024 were selected as the hemorrhage group.Another 90 healthy individuals who underwent physical examinations were selected as the control group.The differences in the levels of NLRP3, Caspase-1 and IL-1β in peripheral blood between the two groups were compared. The National Institutes of Health neurological deficiency score (NHISS) was used to evaluate the degree of neurological deficits of patients in the hemorrhage group. All patients were followed up for 3 months. The prognosis of patients was evaluated by modified Rankin scale (mRS). The statistical analysis was performed using SPSS 20.0 software. The relationship between peripheral blood indexes and blood loss, severity of neurological impairment was analyzed by Spearman correlation analysis. The predictive value of peripheral blood indexes for prognosis was evaluated by receiver operating characteristic (ROC) curves.Results:The expression levels of NLRP3 mRNA (2.67±0.42, 1.04±0.28), Caspase-1 mRNA (1.24±0.26, 0.75±0.14) and IL-1β protein ((24.92±4.97) pg/mL, (13.39±2.35) pg/mL) in the hemorrhage group were higher than those in the control group ( t=31.243, 15.967, 20.126, all P<0.05). When comparing the levels of NLRP3 mRNA, Caspase-1 mRNA and IL-1β in the peripheral blood of patients with different amounts of bleeding, those with massive bleeding were higher than those with moderate bleeding, and those with moderate bleeding were higher than those with mild bleeding (all P<0.05).The Spearman correlation analysis showed that the levels of NLRP3 mRNA, Caspase-1 mRNA and IL-1β in peripheral blood were positively correlated with the amount of bleeding in patients with hemorrhagic stroke ( r=0.646, 0.585, 0.604, all P<0.05). The levels of NLRP3 mRNA, Caspase-1 mRNA and IL-1β in patients with severe neurological deficits were higher than those in patients with moderate and mild neurological deficits, and those in patients with moderate neurological deficits were higher than those in patients with mild neurological deficits (all P<0.05). The results of Spearman correlation analysis showed that the levels of NLRP3 mRNA, Caspase-1 mRNA and IL-1β in peripheral blood were positively correlated with the degree of neurological deficits in patients with hemorrhagic stroke ( r=0.607, 0.522, 0.546, all P<0.05). The expression levels of NLRP3 mRNA, Caspase-1 mRNA and IL-1β in peripheral blood in the poor prognosis group were higher than those in the good prognosis group (all P<0.05). The prediction results indicated that bleeding into the cerebral ventricles, large amount of bleeding, and high expression of NLRP3, Caspase-1 and IL-1β in peripheral blood were independent risk factors for poor prognosis in patients with hemorrhagic stroke (all P<0.05). The area under the ROC curve for the combined assessment of poor prognosis in hemorrhagic stroke by the levels of NLRP3 mRNA, Caspase-1 mRNA and IL-1β was 0.856, which was larger than the areas under the curves of the three indicators detected separately (0.720, 0.703, 0.715, P<0.05). Conclusion:The expressions of peripheral blood NLRP3, Caspase-1 and IL-1β are up-regulated in patients with hemorrhagic stroke, and their high expressions are related to blood loss and the severity of neurological deficit, which also indicate poor prognosis of patients.

This study was aimed at understanding the prevalence and drug resistance status of Salmonella of waterfowl ori-gin in the Guangdong region in the past decade,to guide prevention and control efforts.The drug-sensitive paper slide method was used to conduct drug susceptibility testing on 314 waterfowl-originating Salmonella strains isolated from 238 waterfowl farms in the Guangdong region from 2013 to 2023.The isolated Salmonella strains were most resistant to penicillin,amoxicil-lin,cefradine,and cefazolin in the β-lactam group;sulphadoxine dimethylpyrimidine in the sulphonamide group;and tetracy-cline in the tetracycline group.The resistance rates ranged from 73.57％to 89.49％.The highest sensitivity was observed to amikacin,gentamicin,and kanamycin in the aminoglycoside group,and norfloxacin in the quinolone group,with susceptibility rates all exceeding 50％.The 280 strains of Salmonella showed multi-drug resistance to six classes of antimicrobial drugs and high resistance(as much as 60.83％)to five drug classes.Correlation analysis revealed the highest correlations for florfenicol with gentamicin,and for amoxicillin with penicillin(r=0.650 for both),followed by gentamicin with kanamycin(r=0.620).Salmonella resistance in waterfowl in Guangdong Province was generally severe and showed a complex pattern of drug resist-ance.Detection of waterfowl pathogens should be strengthened to prevent the spread of drug-resistant bacteria and support ra-tional use of antibiotics.This work provides a reference for Salmonella prevention and control in waterfowl farms.

Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.

Objective:To explore the expressions and significance of nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3), cysteinyl aspartate specific proteinase-1 (Caspase-1) and interleukin-1β (IL-1β) in patients with hemorrhagic stroke.Methods:One hundred and three patients with hemorrhagic stroke who visited the Department of Neurosurgery of the Second Affiliated Hospital of Zhengzhou University from January 2022 to January 2024 were selected as the hemorrhage group.Another 90 healthy individuals who underwent physical examinations were selected as the control group.The differences in the levels of NLRP3, Caspase-1 and IL-1β in peripheral blood between the two groups were compared. The National Institutes of Health neurological deficiency score (NHISS) was used to evaluate the degree of neurological deficits of patients in the hemorrhage group. All patients were followed up for 3 months. The prognosis of patients was evaluated by modified Rankin scale (mRS). The statistical analysis was performed using SPSS 20.0 software. The relationship between peripheral blood indexes and blood loss, severity of neurological impairment was analyzed by Spearman correlation analysis. The predictive value of peripheral blood indexes for prognosis was evaluated by receiver operating characteristic (ROC) curves.Results:The expression levels of NLRP3 mRNA (2.67±0.42, 1.04±0.28), Caspase-1 mRNA (1.24±0.26, 0.75±0.14) and IL-1β protein ((24.92±4.97) pg/mL, (13.39±2.35) pg/mL) in the hemorrhage group were higher than those in the control group ( t=31.243, 15.967, 20.126, all P<0.05). When comparing the levels of NLRP3 mRNA, Caspase-1 mRNA and IL-1β in the peripheral blood of patients with different amounts of bleeding, those with massive bleeding were higher than those with moderate bleeding, and those with moderate bleeding were higher than those with mild bleeding (all P<0.05).The Spearman correlation analysis showed that the levels of NLRP3 mRNA, Caspase-1 mRNA and IL-1β in peripheral blood were positively correlated with the amount of bleeding in patients with hemorrhagic stroke ( r=0.646, 0.585, 0.604, all P<0.05). The levels of NLRP3 mRNA, Caspase-1 mRNA and IL-1β in patients with severe neurological deficits were higher than those in patients with moderate and mild neurological deficits, and those in patients with moderate neurological deficits were higher than those in patients with mild neurological deficits (all P<0.05). The results of Spearman correlation analysis showed that the levels of NLRP3 mRNA, Caspase-1 mRNA and IL-1β in peripheral blood were positively correlated with the degree of neurological deficits in patients with hemorrhagic stroke ( r=0.607, 0.522, 0.546, all P<0.05). The expression levels of NLRP3 mRNA, Caspase-1 mRNA and IL-1β in peripheral blood in the poor prognosis group were higher than those in the good prognosis group (all P<0.05). The prediction results indicated that bleeding into the cerebral ventricles, large amount of bleeding, and high expression of NLRP3, Caspase-1 and IL-1β in peripheral blood were independent risk factors for poor prognosis in patients with hemorrhagic stroke (all P<0.05). The area under the ROC curve for the combined assessment of poor prognosis in hemorrhagic stroke by the levels of NLRP3 mRNA, Caspase-1 mRNA and IL-1β was 0.856, which was larger than the areas under the curves of the three indicators detected separately (0.720, 0.703, 0.715, P<0.05). Conclusion:The expressions of peripheral blood NLRP3, Caspase-1 and IL-1β are up-regulated in patients with hemorrhagic stroke, and their high expressions are related to blood loss and the severity of neurological deficit, which also indicate poor prognosis of patients.

Objective To compare the efficacy,economic burden,psychological impact,and quality of life between surgical and medical castration following radical prostatectomy(RP)in patients with very high-risk prostate cancer(VHR PCa).Methods Clinical data of 167 patients with VHR PCa who underwent RP in the Department of Urology,the First Affiliated Hospital of Anhui Medical University during Jul.2019 and Mar.2024 were retrospectively collected.Patients were divided into two groups:the surgical castration group(n=44)and medical castration group(n=123).The effects of different castration methods on the biochemical recurrence(BCR)were analyzed with Cox proportional hazards models.The survival curves of BCR-free and progress to castration-resistant prostate cancer(CRPC)were plotted with the Kaplan-Meier method.The differences in functional assessment of cancer therapy-prostate(FACT-P)and hospital anxiety and depression scale(HADS)between the two groups were evaluated with linear regression model.Results The total costs were significantly lower in the surgical castration group than in the medical castration group[(47 422.0±3 998.3)yuan vs.(59 017.2±8 014.1)yuan,P＜0.001].One month postoperatively,the surgical castration group had significantly lower prostate-specific antigen(PSA)level[0.028(0.010,0.159)ng/mL vs.0.100(0.029,0.895)ng/mL,P=0.002].However,no significant differences were observed in the PSA level between the two groups at 3,6,and 12 months postoperatively,or in PSA nadir and time to nadir(P＞0.05).Cox regression analysis suggested a potentially higher risk of BCR in the medical castration group(HR=2.23),but the difference was not statistically significant(P=0.112).The 1-and 3-year BCR-free survival rates were higher in the surgical castration group(90.9％vs.85.4％;86.4％vs.70.7％,respectively),whereas 1-and 3-year progression-free survival rates were comparable between the two groups(97.7％vs.97.6％;95.5％vs.91.9％),with no significant differences(P＞0.05).No significant differences were found in FACT-P[(57.3±10.2)vs.(57.3±7.6)]or HADS[(12.6±5.1)vs.(11.3±4.8)]scores between the two groups(P＞0.05).Conclusion In VHR PCa patients,surgical castration performed following RP is not inferior to drug castration in terms of PSA control,and potential delay of BCR.It had a lower cost and does not significantly increase the psychological burden.As an underutilized strategy,surgical castration can become an optional option for individualized treatment.

This report described the multidisciplinary management of a preterm infant with congenital tracheal agenesis (TA). The infant, delivered via cesarean section at 32 +5 weeks' gestation, had Apgar scores of 6 and 8 at 1 and 5 minutes, respectively. Although skin color improved after 30 seconds of bag-mask ventilation, the infant exhibited no cry, weak spontaneous breathing, and failed multiple intubation attempts. The patient was transferred to Anhui Children's Hospital of Fudan University under continuous bag-mask positive-pressure ventilation at 3 hours after birth (September 10, 2024). Combined imaging and fiberoptic bronchoscopy confirmed TA (Floyd type Ⅱ/Faro type C) with multiple anomalies, including duodenal atresia, aortic coarctation, and butterfly vertebrae. Whole-genome sequencing revealed a suspected mosaic SCN2A c.5317G>A variant (wild-type parents) and an ERCC5 c.2974C>T heterozygous variant inherited from the mother (homozygous). Following esophageal intubation, invasive mechanical ventilation, and continuous gastrointestinal decompression, respiratory distress significantly improved with a stabilized condition. The infant died 30 hours after birth following treatment withdrawal.