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.

To thoroughly implement the strategic deployment outlined in the Opinions of the Central Committee of the Communist Party of China and the State Council on Promoting the Inheritance and Innovative Development of Traditional Chinese Medicine regarding research on dominant diseases of traditional Chinese medicine and to uphold the development philosophy of equal emphasis on traditional Chinese medicine and western medicine，the China Association of Chinese Medicine has fully played a leading academic role by systematically organizing and conducting a series of academic youth salons on clinical dominant diseases of traditional Chinese medicine. On September 13，2024，the 36^th Youth Salon on Clinical Dominant Diseases was successfully held in Nanjing，focusing on the advantages of traditional Chinese medicine and the integrative traditional Chinese medicine and western medicine in the diagnosis and treatment of erectile dysfunction （ED）. The conference brought together leading experts from traditional Chinese medicine，western medicine，and interdisciplinary fields，facilitating in-depth multidisciplinary discussions that led to key consensus on optimizing traditional Chinese medicine treatment protocols for ED，researching and developing new drugs of traditional Chinese medicine，and advancing interdisciplinary development in traditional Chinese medicine. This salon systematically sorted out the clinical strengths and distinctive features of traditional Chinese medicine in the diagnosis and treatment of ED. Based on current research foundations and clinical needs，it identified key directions for future scientific layout and scientific research tackling： （1） Standardization of syndrome differentiation system of traditional Chinese medicine for ED. （2） Optimization and standardization of intervention methods of integrated traditional Chinese medicine and western medicine. （3） High-quality clinical research guided by evidence-based medicine. （4） In-depth analysis of the pharmacological mechanisms of traditional Chinese medicine in the treatment of ED. （5） Clinical translation and application promotion of new drugs of traditional Chinese medicine. （6） Interdisciplinary integration and innovation in traditional Chinese medicine. For each research direction，key focus areas，expected objectives，and clinical value were further refined，along with the establishment of a scientifically sound priority funding level evaluation system. Therefore，building on the series of salons on the ED-focused dominant diseases of traditional Chinese medicine，this paper provides standardized guidance for clinical practice of traditional Chinese medicine in ED management，effectively contributing to the high-quality development of traditional Chinese medicine. It serves as a valuable reference for national scientific and technological strategic layout， research and development decision-making in new drugs of traditional Chinese medicine，research topic planning，and clinical guideline formulation.

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

OBJECTIVES: To evaluate the effectiveness of single-balloon and double-balloon enteroscopy in diagnosing pediatric small bowel diseases and assess the diagnostic efficacy of computed tomography enterography (CTE) for small bowel diseases using enteroscopy as the reference standard. METHODS: Clinical data from 576 children who underwent enteroscopy at Hunan Children's Hospital between January 2017 and December 2023 were retrospectively collected. The children were categorized based on enteroscopy type into the single-balloon enteroscopy (SBE) group (n=457) and double-balloon enteroscopy (DBE) group (n=119), and the clinical data were compared between the two groups. The sensitivity and specificity of CTE for diagnosing small bowel diseases were evaluated using enteroscopy results as the standard. RESULTS: Among the 576 children, small bowel lesions were detected by enteroscopy in 274 children (47.6%).There was no significant difference in lesion detection rates or complication rates between the SBE and DBE groups (P>0.05), but the DBE group had deeper insertion, longer procedure time, and higher complete small bowel examination rate (P<0.05). The complication rate during enteroscopy was 4.3% (25/576), with 18 cases (3.1%) of mild complications and 7 cases (1.2%) of severe complications, which improved with symptomatic treatment, surgical, or endoscopic intervention. Among the 412 children who underwent CTE, the sensitivity and specificity for diagnosing small bowel diseases were 44.4% and 71.3%, respectively. CONCLUSIONS SBE and DBE have similar diagnostic efficacy for pediatric small bowel diseases, but DBE is preferred for suspected deep small bowel lesions and comprehensive small bowel examination. Enteroscopy in children demonstrates relatively good overall safety. CTE demonstrates relatively low sensitivity but comparatively high specificity for diagnosing small bowel diseases.
Retrospective Studies ; Treatment Outcome ; Double-Balloon Enteroscopy/statistics & numerical data* ; Single-Balloon Enteroscopy/statistics & numerical data* ; Humans ; Male ; Female ; Child ; Operative Time ; Tomography, X-Ray Computed/statistics & numerical data* ; Sensitivity and Specificity ; Intestine, Small/surgery* ; Intestinal Diseases/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.

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*

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.

Objective To analyze the usage of pediatric drugs in 17 pediatric specialty hospitals from 2016 to 2020, and provide reference and guidance for the development of the essential medicine list （EML） for children and the improvement of the National Reimbursement Drug List （NRDL） in China. Methods Based on the pediatric medication monitoring data from 17 children's specialized hospitals reported to the Chinese Medical Economic Information Network (CMEI) of the Chinese Pharmaceutical Association between 2016 and 2020, this study analyzes the overall situation of the sample hospitals and the clinical use of pediatric drugs according to the major categories of the Anatomical Therapeutic Chemical Classification System （ATC）. Results In the various ATC categories, the trend of systemic use of anti-infective drugs decreasing was significant in the average hospital expenditure, while the trend of respiratory and digestive system and metabolic drugs decreasing was significant in the average hospital DDDS. In 2020, the average number of hospital grade standards for essential drugs （2018 version） accounted for 15.82% of the total number of drug use standards, while the average number of hospital grade standards for medical insurance （2019 version） accounted for 8.23% of the total number of drug use standards. Conclusion The use of pediatric medication in sample hospitals from 2016 to 2020 was generally reasonable, and there would still a certain gap between the actual clinical usage habits with the existing EML and NRDL，which still need to be adjusted.

Objective:To observe the effects of ear acupressure combined with acupoint application on serum inflammatory factors,pain and psychological status of children with limb fractures.Methods:By using random number table method,60 children with limb fracture who were admitted to Qiantang Campus of Zhejiang Provincial Traditional Chinese Medicine Hospital from February 2022 to August 2024 were divided into control group(received conventional treatment combined with acupoint application)and experimental group(combined with ear acupressure based on the control group),with 30 cases in each group.Pain and swelling degree of the affected limb,anxiety and depression[Screening Checklist for Childhood Anxiety Disorders(SCARED),Depression self-rating scale for children(DSRSC)],inflammatory factors[High sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1(IL-1)]and family satisfaction rate were compared between the two groups.Results:The scores of visual analogue scale(VAS),SCARED and DSRSC in the experimental group were lower than those in the control group at 1 week and 4 weeks after treatment(P＜0.05).Swelling degree of the affected limb in the experimental group was better than that in the control group at 4 weeks after treatment(P＜0.05).hs-CRP,IL-1,IL-6 and TNF-α in the experimental group were lower than those in the control group at 4 weeks after treatment(P＜0.05).The family satisfaction rate in the experimental group was higher than that in the control group(P＜0.05).Conclusion:Ear acupressure combined with acupoint application therapy for children with limb fractures can significantly alleviate postoperative pain,promote swelling reduction,effectively reduce inflammation,and improve anxiety and depression,with high treatment satisfaction.