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 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*

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*

OBJECTIVE: The aim of this study is to evaluate the clinical efficacy of Oxalicao Formula combined　with transacupuncture in the treatment of chronic nonbacterial prostatitis （CNP）characterized by dampness-heat stasis. METHODS: A total of 70 patients diagnosed with CNP and characterized by dampness-heat stasis were randomly divided into control group and treatment group, with 35 cases in each group. The patients in control group received Qianlie Beixi capsules． Ｗhile the patients in　treatment group were administered with oxalis decoction in conjunction with acupuncture therapy　which lasted for 8 weeks. Pre- and post-treatment evaluations for NIH-Chronic Prostatitis Symptom Index (NIH-CPSI), Traditional Chinese Medicine (TCM) symptom scores, urodynamic parameters, immune cell subsets and inflammatory factors were performed. RESULTS: Ultimately, 65 patients completed the study　with 33 in the treatment group and 32 in the control group. After 8 weeks of intervention, The patients in both of groups demonstrated significant improvements (P<0.05). Specifically, remarkable reductions in the NIH-CPSI total score　including pain score, urination score, quality of life impact score, TCM symptom score and inflammatory cytokine levels　were observed. Additionally, there were upward trend　in maximum and average urinary flow rates as well as the CD4+/CD8+ ratio of immune cells(P<0.05). Compared to the control group, the treatment group exhibited superior outcomes in reducing the NIH-CPSI total score, pain score, urination score, quality of life impact score, TCM symptom score, and inflammatory cytokine levels, and increasing in　CD4+/CD8+ ratios， maximum and average urine flow rates(P<0.05). CONCLUSION The combination of Oxalicao Formula and transacupuncture for treating CNP characterized by dampness-heat stasis demonstrates significant therapeutic benefits, which has considerable clinical application value.
Humans ; Male ; Prostatitis/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Acupuncture Therapy ; Medicine, Chinese Traditional ; Chronic Disease ; Treatment Outcome ; Adult

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 explore and analyze the expression and prognostic value of serum vitamin D(VitD),fer-ritin(FRT)and heparin-binding epidermal growth factor(HB-EGF)in sepsis patients.Methods 86 sepsis patients who were admitted to the intensive care unit(ICU)of a hospital from January 2021 to January 2022 were selected as the case group,and 60 non-sepsis patients in the ICU were selected as the control group.According to the prognosis of sepsis patients one month later,patients were divided into survival group and death group.Patient's serum upon admission was taken,levels of serum VitD,FRT and HB-EGF were detected,the correlation with the prognosis of sepsis patients was analyzed,and the prognostic value was evaluated by area under curve(AUC)of receiver opera-ting characteristic curve.Results Levels of white blood cell count(WBC),C-reactive protein(CRP),procalcitonin(PCT),tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-1β and FRT of case group were all higher than those of non-sepsis patients in the control group,while the VitD and HB-EGF levels were lower than those of non-sepsis patients in the control group,differences were all statistically significant(all P＜0.05).One month follow-up on the prognosis of sepsis patients showed that 55 patients survived and 31 died.Acute physiology and chronic health evaluationⅡ(APACHE IⅡ)score,sequential organ failure assessment(SOFA)score,PCT,TNF-α,L-1βand FRT score in patients in the death group were all higher than those in patients in the survival group,while VitD and HB-EGF were lower than patients in the survival group,differences were all statistically significant(all P＜0.05).The Pearson correlation analysis results showed that VitD were negatively correlated with APACHE Ⅱ score,SOFA score,WBC,CRP,PCT and TNF-α(all P＜0.05),HB-EGF was negatively correlected with APACHE Ⅱ,score,CRP,PCT,TNF-α,IL-6 and IL-1β(all P＜0.05);while FRT was positively correlated with APACHE Ⅱscores,CRP,PCT,TNF-α,IL-6 and IL-1β(all P＜0.05).The AUC,sensitivity,and specificity of combined de-tection of serum VitD,FRT and HB-EGF in predicting the prognosis of sepsis patients were 0.82(95％CI:0.72-0.86),84.39％,and 69.35％,respectively.Conclusion Serum levels of VitD and HB-EGF are lower and FRT is higher in sepsis patients,their expression levels are closely related to patient prognosis,and have good predictive value for predicting the prognosis of sepsis patients.

By reviewing the ancient and modern literature， the name， origin， scientific name evolution， place of origin， quality， harvesting， processing， efficacy and toxicity of Asteris Radix et Rhizoma（ARR） were systematically sorted out， so as to provide reference for the development and utilization of the relevant famous classical formulas. According to textual research， ARR was first contained in Shennong Bencaojing， all generations are Ziwan for its proper name， and there are still aliases such as Ziyuan， Ziqian and Xiaobianer. Its mainstream origin in successive generations was Aster tataricus， and there are also Ligularia fischeri and others in local area of use. The medicinal parts of ARR are root and rhizome， but in modern times， the rhizome is mostly used for propagation and cultivation， so some of ARR medicinal materials only have the root without the rhizome. The earliest recorded ancient origin of ARR was now Fangxian（Hubei）， Zhengding and Handan（Heibei）， then the range of production areas gradually expanded， the mainstream production areas from the Song dynasty to the Ming and Qing dynasties included Hebei， Jiangsu， Anhui， Henan and other places， since modern times， two major producing areas have been formed in Anguo， Hebei province and Bozhou， Anhui province. From the quality evaluation， it is clear that from ancient times， flexible roots and purple color are the best. The ancient harvesting was mainly in lunar February or March， and then dried in the shade， and the modern harvesting is mostly in spring and autumn， and the roots are braided into pigtails and then dried in the sun or dried in the sun after 1-2 d. The ancient and modern processing method of ARR are basically the same， mainly honey processing， there are still methods of frying， steaming， vinegar sizzling， etc. Based on the results， it is recommended that the dried roots and rhizomes of A. tataricus should be used in clinical and the development of related famous classical formulas， and those whose original formulas specify the processing requirements can be processed according to the relevant requirements， while whose processing requirements are not specified should be used in the form of raw products.

By consulting the ancient and moderm literature， this paper makes a textual research on the name， origin， quality evaluation， harvesting and processing of Olibanum， so as to provide a basis for the development of the famous classical formulas containing this medicinal material. According to the herbal textual research， the results showed that Olibanum was first described as a medicinal material by the name of Xunluxiang in Mingyi Bielu（《名医别录》）， until Ruxiang had been used as the correct name since Bencao Shiyi（《本草拾遗》） in Tang dynasty. The main origin was Boswellia carterii from Burseraceae family. The mainly producing areas in ancient description were ancient India and Arabia， while the modern producing areas are Somalia， Ethiopia and the southern Arabian Peninsula. The medicinal part of Olibanum in ancient and modern times is the resin exuded from the bark， which has been mainly harvested in spring and summer. It is concluded that the better Olibanum has light yellow， granular， translucent， no impurities such as sand and bark， sticky powder and aromatic smell. There were many processing methods in ancient times， including cleansing（water flying， removing impurities）， grinding（wine grinding， rush grinding）， frying（stir-frying， rush frying， wine frying）， degreasing， vinegar processing， decoction. In modern times， the main processing methods are simplified to cleansing， stir-frying and vinegar processing. Nowadays， the commonly used specifications include raw， fried and vinegar-processed products. Among the three specifications， raw products is the Olibanum after cleansing， fried products is a kind of Olibanum processed by frying method， vinegar-processed products is the processed products of pure frankincense mixed with vinegar. Based on the research results， it is recommended to select the resin exuded from the bark of B. carterii for the famous classical formulas such as Juanbitang containing Olibanum， processing method should be carried out in accordance with the processing requirements of the formulas， otherwise used the raw products if the formulas without clear processing requirements.

By consulting ancient and modern literature， the herbal textual research of Farfarae Flos has been conducted to verify the name， origin， producing area， quality evaluation， harvesting and processing methods， so as to provide reference for the development and utilization of the famous classical formulas containing Farfarae Flos. According to the research， the results showed that Farfarae Flos was first described as a medicinal material by the name of Kuandonghua in Shennong Bencaojing（《神农本草经》）， and the name was used and justified by later generations. The main origin was the folwer buds of Tussilago farfara， in addition， the flower buds of Petasites japonicus were used as medicine in ancient times. The ancient harvesting time of Farfarae Flos was mostly in the twelfth month of the lunar calendar， and the modern harvesting time is in December or before the ground freeze when the flower buds have not been excavated. Hebei， Gansu， Shaanxi are the authentic producing areas with the good quality products. Since modern times， its quality is summarized as big， fat， purple-red color， no pedicel is better. Processing method from soaking with licorice water in the Northern and Southern dynasties to stir-frying with honey water followed by micro-fire in the Ming dynasty， and gradually evolved to the modern mainstream processing method of honey processing. Based on the research results， it is suggested that the dried flower buds of T. farfara， a Compositae plant， should be selected for the development of famous classical formulas containing Farfarae Flos， and the corresponding processed products should be selected according to the specific processing requirements of the formulas， and raw products are recommended for medicinal use without indicating processing requirements.