ObjectiveBased on traditional quality evaluation of Gardeniae Fructus（GF） recorded in historical materia medica， this study systematically compared the quality differences between wild and cultivated GF from morphological characteristics， microscopic features， and contents of primary and secondary metabolites. MethodsVernier calipers and analytical balances were used to measure the length， diameter and individual fruit weight of wild and cultivated GF， and the aspect ratio was calculated. A colorimeter was used to determine the chromaticity value of wild and cultivated GF， and the paraffin sections of them were prepared by safranin-fast green staining and examined under an optical microscope to observe their microstructure. Subsequently， the contents of water-soluble and alcohol-soluble extracts of wild and cultivated GF were detected by hot immersion method under the general rule 2201 in volume Ⅳ of the 2020 edition of the Pharmacopoeia of the People's Republic of China， the starch content was measured by anthrone colorimetric method， the content of total polysaccharides was determined by phenol-sulfuric acid colorimetric method， the sucrose content was determined by high performance liquid chromatography coupled with evaporative light scattering detection（HPLC-ELSD）， and the contents of representative components in them were measured by ultra-performance liquid chromatography（UPLC）. Finally， correlation analysis was conducted between quality traits and phenotypic traits， combined with multivariate statistical analysis methods such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， key differential components between wild and cultivated GF were screened. ResultsIn terms of traits， the wild GF fruits were smaller， exhibiting reddish yellow or brownish red hues with significant variation between batches. While the cultivated GF fruits are larger， displaying deeper orange-red or brownish red. The diameter and individual fruit weight of cultivated GF were significantly greater than those of wild GF， while the blue-yellow value（b^*） of wild GF was significantly higher than that of cultivated GF. In the microstructure， the mesocarp of wild GF contained numerous scattered calcium oxalate cluster crystals， while the endocarp contained stone cell class round， polygonal or tangential prolongation， undeveloped seeds were visible within the fruit. In contrast， the mesocarp of cultivated GF contained few calcium oxalate cluster crystals， or some batches exhibited extremely numerous cluster crystals. The stone cells in the endocarp were predominantly round-like， with the innermost layer arranged in a grid pattern. Seeds were basically mature， and only a few immature seeds existed in some batches. Regarding primary metabolite content， wild GF exhibited significantly higher total polysaccharide level than cultivated GF（P<0.01）. In category-specific component content， wild GF exhibited significantly higher levels of total flavonoids and total polyphenols compared to cultivated GF（P<0.01）. Analysis of 12 secondary metabolites revealed that wild GF exhibited significantly higher levels of Shanzhiside， deacetyl asperulosidic acid methyl ester， gardenoside and chlorogenic acid compared to cultivated GF（P<0.01）. Conversely， the contents of genipin 1-gentiobioside， geniposide and genipin were significantly lower in wild GF（P<0.01）. ConclusionThere are significant differences between wild and cultivated GF in terms of traits， microstructure， and contents of primary and secondary metabolites. At present， the quality evaluation system of cultivated GF remains incomplete， and this study provides a reference for guiding the production of high-quality GF medicinal materials.

OBJECTIVE: To evaluate the effectiveness of the channel-assisted minimally invasive repair (CAMIR) technique combined with flexor hallucis longus (FHL) tendon transfer in the treatment of Achilles tendon sleeve avulsion. METHODS: A retrospective analysis was conducted on 17 patients with Achilles tendon sleeve avulsion who underwent CAMIR technique combined with FHL transfer between January 2019 and January 2023. The cohort comprised 13 males and 4 females, aged 32 to 65 years (mean, 49.7 years). Etiologies included sports-related injuries in 15 cases and blunt trauma in 2 cases. The interval from injury to surgery ranged from 4 to 368 days (median, 15 days). All patients exhibited calcification at the Achilles tendon insertion site, with 7 cases complicated by Haglund deformity. Postoperative complications were meticulously monitored, and tendon healing was assessed via MRI. Clinical outcome were evaluated using the visual analogue scale (VAS) score for pain, Tegner activity level rating scale, ankle activity score (AAS), American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, Victorian Institute of Sport Assessment-Achilles (VISA-A) score, and subjective clinical scoring systems preoperatively and at last follow-up. RESULTS: The operation time was 50-62 minutes (mean, 56 minutes), and the intraoperative blood loss was 5-50 mL (mean, 19.7 mL). All patients were followed up 12-67 months (mean, 38 months). No postoperative complication, such as Achilles tendon re-rupture, incision infection, deep vein thrombosis, heel raise insufficiency, or sural nerve injury, was observed. At last follow-up, MRI examination confirmed satisfactory tendon healing in all cases. Significant improvements were noted in VAS scores, Tegner activity level rating scale, AAS scores, AOFAS ankle-hindfoot scores, and VISA-A scores compared to preoperative ones ( P<0.05). At last follow-up, the subjective clinical score ranged from 6 to 10 (median, 9). CONCLUSION The CAMIR technique combined with FHL tendon transfer is a good treatment for repair of Achilles tendon sleeve avulsion, with good recovery of ankle function and few complications.
Humans ; Achilles Tendon/diagnostic imaging* ; Middle Aged ; Male ; Female ; Tendon Transfer/methods* ; Minimally Invasive Surgical Procedures/methods* ; Adult ; Retrospective Studies ; Aged ; Treatment Outcome ; Tendon Injuries/surgery*

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.

With the deepening of molecular biology and cell biology research,the regulatory mechanism of autophagy has been gradually revealed,providing new ideas for the treatment of numerous diseases.Autophagy may be closely related to pathological changes such as apoptosis resistance of fibroblast-like synoviocytes,disturbances in bone metabolic homeostasis,and antigen presentation,the regulation of autophagy homeostasis may be an important approach for the treatment of rheumatoid arthritis(RA).In this paper,we provide a review on the pathological mechanism of autophagy in RA,with a view to providing a theoretical basis for later studies.

A primary hallmark of pathological cardiac hypertrophy is excess protein synthesis due to enhanced translational activity. However, regulatory mechanisms at the translational level under cardiac stress remain poorly understood. Here we examined the translational regulations in a mouse cardiac hypertrophy model induced by transaortic constriction (TAC) and explored the conservative networks versus the translatome pattern in human dilated cardiomyopathy (DCM). The results showed that the heart weight to body weight ratio was significantly elevated, and the ejection fraction and fractional shortening significantly decreased 8 weeks after TAC. Puromycin incorporation assay showed that TAC significantly increased protein synthesis rate in the left ventricle. RNA-seq revealed 1,632 differentially expressed genes showing functional enrichment in pathways including extracellular matrix remodeling, metabolic processes, and signaling cascades associated with pathological cardiomyocyte growth. When combined with ribosome profiling analysis, we revealed that translation efficiency (TE) of 1,495 genes was enhanced, while the TE of 933 genes was inhibited following TAC. In DCM patients, 1,354 genes were upregulated versus 1,213 genes were downregulated at the translation level. Although the majority of the genes were not shared between mouse and human, we identified 93 genes, including Nos3, Kcnj8, Adcy4, Itpr1, Fasn, Scd1, etc., with highly conserved translational regulations. These genes were remarkably associated with myocardial function, signal transduction, and energy metabolism, particularly related to cGMP-PKG signaling and fatty acid metabolism. Motif analysis revealed enriched regulatory elements in the 5' untranslated regions (5'UTRs) of transcripts with differential TE, which exhibited strong cross-species sequence conservation. Our study revealed novel regulatory mechanisms at the translational level in cardiac hypertrophy and identified conserved translation-sensitive targets with potential applications to treat cardiac hypertrophy and heart failure in the clinic.
Animals ; Humans ; Cardiomegaly/physiopathology* ; Ribosomes/physiology* ; Protein Biosynthesis/physiology* ; Mice ; Cardiomyopathy, Dilated/genetics* ; Ribosome Profiling

Objective To investigate the effect of an intelligent telerehabilitation developed with reinforcement theory on the postoperative functional recovery and return to sport in patients after reconstructive surgery of anterior cruciate ligament.Methods By using the convenience sampling method,120 patients after reconstructive surgery of anterior cruciate ligament at a tertiary general hospital in Wuhan from June 2022 to June 2023 were selected as the research subjects.Sixty patients admitted to our hospital between June 2022 and December 2022 were assigned to a control group,while another 60 patients admitted to our hospital between January 2023 and June 2023 were assigned to an trial group.The patients in the control group received conventional surgical treatment,nursing care and instructions for rehabilitation,whereas additional rehabilitation based on the intelligent telerehabilitation developed with reinforcement theory was given to the patients in the trial group.The two groups were compared in terms of postoperative knee function and compliance with rehabilitation exercise.Results The compliance of the trial group with home rehabilitation training was higher than that of the control group.The comparison between the two groups showed a statistically significant difference(P<0.05).12 months after surgery,patients in the trial group exhibited higher scores in International Knee Documentation Committee Subjective knee form(IKDC)and Lysholm and Gillquist knee scores compared with those in the control group(both P<0.05.Also,the patients in trial group showed lower incidences of pain,swelling and joint instability compared with those in the control group(all P<0.05).At 12 months after surgery,the patients in trial group showed better capability to perform daily activities and participate in sports in comparison with those in the control group(both P<0.05).Conclusion The intelligent telerehabilitation based on reinforcement theory can improve the compliance of patient with rehabilitation.It therefore is able to reduce incidences of postoperative complications such as pain,swelling,knee instability and locking in patients who had the surgery for reconstruction of anterior cruciate ligament.It also enhances the function recovery of knee,and helps patients to resume the activities in life and sports.

This study aims to comprehensively evaluate the analytical performance and clinical application value of an acridinium ester-based chemiluminescence assay for detecting heparin-binding protein (HBP), providing more accurate laboratory evidence for the early diagnosis of infections and sepsis. The analytical performance of the HBP detection kit based on acridinium ester chemiluminescence was verified in Hangzhou Hospital of Traditional Chinese Medicine in January 2024 to June 2024, including limit of blank (LoB), accuracy, precision, linear range, anti-interference ability, and clinical diagnostic concordance. The potential of this assay in early diagnosis and treatment monitoring of sepsis was assessed. HBP levels were measured in 97 patients with sepsis and 160 healthy controls, and intergroup differences were analyzed using the Mann-Whitney U test. The results showed that the LoB of the HBP detection kit based on acridinium ester chemiluminescence was 0.10 RLU, and low-concentration sample testing showed good discrimination. In the accuracy evaluation, the regression equation between the test reagent and the comparator was y=1.015 2 x-2.850 8 (R2=0.995 1). For precision, the CV in intra-assay was ≤3.51%, and the CV in inter-assay was ≤4.18%. Within the linear range of 0.42-493.46 ng/ml, the regression equation was y=0.996 9 x+3.066 0 (R2=0.999 1). In interference experiments, the relative deviation was <3%. Clinically, the median HBP concentration in the sepsis group (median: 121.1 ng/ml) was significantly higher than in the control group (median: 6.3 ng/ml, P<0.000 1), with a diagnostic sensitivity of 98.97% and specificity of 96.25%. Age stratification had no effect on HBP levels ( U=448 ,P=0.780 0). In conclusion,the acridinium ester-based chemiluminescence assay requires only about 10 minutes to complete the detection and deliver results, demonstrating acceptable sensitivity, precision, and anti-interference capability. Its wide linear range and rapid detection meet emergency testing needs. Clinical validation confirms HBP′s extremely high sensitivity and specificity for sepsis diagnosis, supporting its role as a key marker for early diagnosis, treatment monitoring, and prognosis assessment.

Objective:To investigate the efficacy and safety of intravesical injections of botulinum toxin A (BTX-A) for the treatment of pediatric refractory urinary frequency and incontinence (UFI), and to analyze the factors predicting the therapeutic effect of BTX-A injections.Methods:A retrospective case series study was made on 35 children with UFI [(12.3±4.2) years old], including 13 males (37.1%) and 22 females (62.9%), treated in the First Affiliated Hospital of Zhengzhou University from January 2021 to March 2024.Urotherapy and drug treatments were ineffective in all children, who then received intravesical injections of BTX-A.The urodynamic study (UDS) was performed 1 week before treatment and 3 months after treatment, and the Overactive Bladder Symptom Score (OABSS) and Incontinence Quality of Life (I-QOL) were collected.Perioperative and postoperative adverse events were also recorded.A global response assessment (GRA) score of ≥2 at 3 months postoperatively was defined as effective treatment.According to the postoperative GRA score, the patients were divided into effective and ineffective groups to explore the predictive factors affecting the outcome of BTX-A treatment, such as age, gender, preoperative urodynamic parameters, and the types of urinary incontinence. t-test was used to compare quantitative data such as age, UDS parameters, OABSS, and I-QOL scores.The comparison of count data such as gender and urinary incontinence types was conducted using Fisher′s exact test. Results:The bladder compliance, bladder capacity ratio, OABSS and I-QOL scores of patients significantly improved after BTX-A injection (all P<0.05).The 77.1% (27/35) of the patients were satisfied with BTX-A treatment effects.The main adverse event during the follow-up was a temporary increase in postvoid residual urine after injecting BTX-A (7 cases), which was alleviated by the Creade action or clean intermittent catheterization.There was significant difference in age [(13.00±4.32) years vs.(10.00±2.67) years] and preoperative bladder compliance [(11.21±5.74) mL/cmH 2O vs.(5.13±2.42) mL/cmH 2O] between effective (27 cases) and ineffective groups (8 cases) ( t=2.383, 2.899, all P<0.05).The differences in preoperative bladder capacity ratio, maximum filling detrusor pressure, postvoid residual urine, voiding efficiency, gender, and the types of urinary incontinence were not statistically significant between the two groups (all P>0.05). Conclusions:Intravesical injection of BTX-A is a safe and effective treatment for children with refractory UFI.A young age and poor bladder compliance at treatment are associated with poor prognosis of BTX-A treatment.

This study aims to comprehensively evaluate the analytical performance and clinical application value of an acridinium ester-based chemiluminescence assay for detecting heparin-binding protein (HBP), providing more accurate laboratory evidence for the early diagnosis of infections and sepsis. The analytical performance of the HBP detection kit based on acridinium ester chemiluminescence was verified in Hangzhou Hospital of Traditional Chinese Medicine in January 2024 to June 2024, including limit of blank (LoB), accuracy, precision, linear range, anti-interference ability, and clinical diagnostic concordance. The potential of this assay in early diagnosis and treatment monitoring of sepsis was assessed. HBP levels were measured in 97 patients with sepsis and 160 healthy controls, and intergroup differences were analyzed using the Mann-Whitney U test. The results showed that the LoB of the HBP detection kit based on acridinium ester chemiluminescence was 0.10 RLU, and low-concentration sample testing showed good discrimination. In the accuracy evaluation, the regression equation between the test reagent and the comparator was y=1.015 2 x-2.850 8 (R2=0.995 1). For precision, the CV in intra-assay was ≤3.51%, and the CV in inter-assay was ≤4.18%. Within the linear range of 0.42-493.46 ng/ml, the regression equation was y=0.996 9 x+3.066 0 (R2=0.999 1). In interference experiments, the relative deviation was <3%. Clinically, the median HBP concentration in the sepsis group (median: 121.1 ng/ml) was significantly higher than in the control group (median: 6.3 ng/ml, P<0.000 1), with a diagnostic sensitivity of 98.97% and specificity of 96.25%. Age stratification had no effect on HBP levels ( U=448 ,P=0.780 0). In conclusion,the acridinium ester-based chemiluminescence assay requires only about 10 minutes to complete the detection and deliver results, demonstrating acceptable sensitivity, precision, and anti-interference capability. Its wide linear range and rapid detection meet emergency testing needs. Clinical validation confirms HBP′s extremely high sensitivity and specificity for sepsis diagnosis, supporting its role as a key marker for early diagnosis, treatment monitoring, and prognosis assessment.