ObjectiveThe nucleolar protein PES1 (Pescadillo homolog 1) plays critical roles in ribosome biogenesis and cell cycle regulation, yet its involvement in cellular senescence remains poorly understood. This study aimed to comprehensively investigate the functional consequences of PES1 suppression in cellular senescence and elucidate the molecular mechanisms underlying its regulatory role. MethodsInitially, we assessed PES1 expression patterns in two distinct senescence models: replicative senescent mouse embryonic fibroblasts (MEFs) and doxorubicin-induced senescent human hepatocellular carcinoma HepG2 cells. Subsequently, PES1 expression was specifically downregulated using siRNA-mediated knockdown in these cell lines as well as additional relevant cell types. Cellular proliferation and senescence were assessed by EdU incorporation and SA-β-gal staining assays, respectively. The expression of senescence-associated proteins (p53, p21, and Rb) and SASP factors (IL-6, IL-1β, and IL-8) were analyzed by Western blot or qPCR. Furthermore, Northern blot and immunofluorescence were employed to evaluate pre-rRNA processing and nucleolar morphology. ResultsPES1 expression was significantly downregulated in senescent MEFs and HepG2 cells. PES1 knockdown resulted in decreased EdU-positive cells and increased SA‑β‑gal-positive cells, indicating proliferation inhibition and senescence induction. Mechanistically, PES1 suppression activated the p53-p21 pathway without affecting Rb expression, while upregulating IL-6, IL-1β, and IL-8 production. Notably, PES1 depletion impaired pre-rRNA maturation and induced nucleolar stress, as evidenced by aberrant nucleolar morphology. ConclusionOur findings demonstrate that PES1 deficiency triggers nucleolar stress and promotes p53-dependent (but Rb-independent) cellular senescence, highlighting its crucial role in maintaining nucleolar homeostasis and regulating senescence-associated pathways.

This paper summarizes the exploration process and academic significance of the academic thought of Zhou Zhongying,a master of traditional Chinese medicine,who took the creation of a new system of TCM pathogenesis theory as the core,and interprets its theoretical connotation.As a pioneer in the construction of higher education textbooks for traditional Chinese medicine,Professor Zhou Zhongying created the outline of TCM internal medicine viscera differentiation,persisted in carrying out innovative research on patho-genesis theory,achieved fruitful academic results,and enriched and developed the academic system of TCM theory.In the clinical di-agnosis and treatment of exogenous febrile diseases and acute and difficult internal injuries,he systematically created new pathogenesis theories such as stasis-heat theory and cancer toxicity theory.Based on this,the legislation of medication can improve the clinical effi-cacy,and it is realized that identifying the pathogenesis is the key link in syndrome differentiation and treatment.In his later years,Professor Zhou Zhongying,guided by the holistic view,proposed the"thirteen pathogenesis"and constructed a new system of TCM pathogenesis differentiation,highlighting the guiding value of complex pathogenesis and the causal chain of pathogenesis elements to complex clinical diseases and syndromes,forming a theory with the idea of"examining syndromes and seeking pathogenesis,activating syndrome differentiation"as its soul.This theory breaks through the rigid thinking of syndrome differentiation and treatment based on a single pathogenesis or fixed syndrome type,reconstructs the theoretical framework of TCM with the idea of holistic view,and is a major academic innovation in modern TCM.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

The traditional Chinese medicine Atractlodis Rhizoma is the dried rhizome of the Asteraceae herbal plant Atractylodes lancea, and it has the functions of drying dampness and strengthening the spleen, removing wind and dissipating cold, and brightening the eyes. The sesquiterpenoids in A. lancea are the main ingredients of its pharmacological activities in clinical practice, including atractylone, β-eudesmol, and hinesol, which possess anti-inflammation, antibacterial, antiviral, and hepatoprotective effects. This study focused on the biosynthesis of sesquiterpenoids in A. lancea, summarized the proportion of the main active ingredients in A. lancea from the genuine region and the non-genuine region, elaborated on the research progress of genes related to biosynthesis pathways, and systematically sorted out the biotic and abiotic factors affecting their biosynthesis, so as to provide a theoretical basis for further research on the biosynthetic mechanism of sesquiterpenoids in A. lancea and development of high-quality medicinal materials of A. lancea.
Atractylodes/metabolism* ; Sesquiterpenes/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Biosynthetic Pathways

OBJECTIVE: To retrospectively analyze the clinical efficacy of anterior cruciate ligament (ACL) reconstruction combined with anterolateral complex repair and ACL reconstruction combined with ALL reconstruction in the treatment of anterior cruciate ligament injuries with high-grade pivot shift. METHODS: From January 2018 to June 2022, 49 patients combined ACL and ALL injuries with high-grade pivot shift were retrospectively studied from three hospitals, 29 of them underwent ACL reconstruction with anterolateral complex repair (repair group), including 23 males and 6 females with an average age of (27.5±4.8) years old, ranged from 20 to 37 years old;the injured sides were 13 on the left and 16 on the right, and 11 patients were suffered with meniscus injury. The other 20 patients underwent ACL and ALL reconstruction (reconstruction group) including 17 males and 3 females with the mean age of (27.1±4.5) years old, ranged from 20 to 38 years old;the injured sides were 8 on the left and 12 on the right, and 6 patients were suffered with meniscus injury. Knee stability (pivot shift test, KT-2000), range of motion, knee function (Lysholm scoring scale, Cincinnati sports activity scale (CSAS) scoring scale, and Tegner activity level score between two groups were compared. RESULTS: A total of 49 patients were followed up, the repair group receiving 13 to 20(15.3±1.8) months and the reconstruction group receiving 12 to 21(16.0±2.2) months. There was no statistically significant difference in the preoperative pivot shift test grading distribution between two groups (P>0.05). At the last postoperative follow-up, there were 24 patients with grade 0 and 5 patients with grade 1 in the repair group, and there were 18 patients with grade 0 and 2 patients with grade 1 in the reconstruction group, there is no significant difference in the distribution of axial shift test grading between two groups(P>0.05). The preoperative KT-2000 tibial displacement of two groups were (9.39±0.77) mm (repair group) and (9.14±0.78) mm (reconstruction group) respectively, with no statistically significant difference (P>0.05). At the final postoperative follow-up, there were 24 patients with KT-2000 tibial displacement <3 mm and 5 patients with 3 to 5 mm in the repair group, while 18 patients with <3 mm and 2 patients with 3 to 5 mm in the reconstruction group, KT-2000 tibial displacement distribution of two groups was no significant difference (P>0.05), but the KT-2000 tibial displacement in the reconstruction group (1.30±0.86) mm was significantly smaller than that in the repair group (1.99±1.11) mm (P<0.05). The final postoperative follow-up range of motion of the contralateral side knee between two groups was no significant difference (P>0.05). The range of motion of the suffering knee in the repair group was less than that in the reconstruction group (P<0.05). There was no significant difference in preoperative Lysholm and CSAS scores between two groups (P>0.05). At the final postoperative follow-up, both groups showed significant improvement in Lysholm and CSAS scores, while the Lysholm and CSAS scores of the reconstruction group were better than those of the repair group, and the difference was statistically significant (P<0.05). Significant differences was found in Tegner scores between two groups, which 16 patients in the repair group returned to their pre-injury activity level, and 17 patients in the reconstruction group returned to their pre-injury level (P<0.05). CONCLUSION Compared to anterolateral complex repair, combined ACL and ALL reconstruction in the treatment of ACL injuries with high-grade pivot shift results in better knee joint function and stability. This is advantageous in reducing the risk of ACL reconstruction failure.
Humans ; Male ; Female ; Adult ; Anterior Cruciate Ligament Reconstruction/methods* ; Anterior Cruciate Ligament Injuries/surgery* ; Young Adult ; Retrospective Studies ; Anterior Cruciate Ligament/surgery* ; Range of Motion, Articular

Child ; Humans ; Acquired Immunodeficiency Syndrome/drug therapy* ; Retrospective Studies ; Anti-Retroviral Agents/therapeutic use* ; HIV Infections/epidemiology* ; China/epidemiology* ; Anti-HIV Agents/therapeutic use*

The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.
Rats ; Mice ; Animals ; Chronic Pain/metabolism* ; Rats, Sprague-Dawley ; Ganglia, Spinal/metabolism* ; Ligands ; Signal Transduction ; Hyperalgesia/metabolism* ; Drugs, Chinese Herbal

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

Objective:To explore the value of quantitative parameters of enhanced MRI in predicting the establishment of inferior vena cava collateral circulation in patients with renal cell carcinoma and inferior vena cava tumor thrombus.Methods:Sixty-seven patients with renal cell carcinoma and inferior vena cava tumor thrombus who underwent radical resection and inferior vena cava venography in First Medical Center, PLA General Hospital from May 2006 to January 2021 were included retrospectively. According to the results of inferior vena cava venography, the patients were divided into two groups: the well-established collateral circulation group ( n=41) and the poor-established collateral circulation group ( n=26). Quantitative parameters were measured on preoperative enhanced MRI images, including tumor size, the maximum diameter of bilateral lumbar veins, the length of tumor thrombus, and the long and short diameters of tumor thrombus. Student′s t test or Mann-Whitney U test was used for comparison between the two groups. The independent risk factors related to the establishment of collateral circulation were obtained by binary logistic regression analysis and the model was established. The receiver operating characteristic curve was employed to evaluate MRI quantitative parameters and the logistic model, and the area under the curve (AUC) was compared by the DeLong test. Results:Between the well-established collateral circulation group and the poor-established collateral circulation group, the maximum diameter of the right lumbar vein, the maximum diameter of the left lumbar vein, the length of the tumor thrombus, the long diameter of the tumor thrombus, and the short diameter of the tumor thrombus were different significantly ( P<0.05). There was no significant difference in the tumor size between the two groups ( t=0.30, P=0.766). The AUC of the maximum diameters of the right lumbar veins and left lumbar veins, length of tumor thrombus, long and short diameters of tumor thrombus in predicting the collateral circulation were 0.917 (95%CI 0.824-0.971), 0.869 (95%CI 0.764-0.939), 0.756 (95%CI 0.636-0.853), 0.886 (95%CI 0.785-0.951), and 0.906 (95%CI 0.809-0.963). The AUC of the maximum diameter of the right lumbar vein and the short diameter of the tumor thrombus were larger than those of the length of the tumor thrombus, and the differences were statistically significant ( Z=2.25, 2.04, P=0.025, 0.041), but the AUC between other parameters had no significant difference ( P>0.05). The maximum diameter of the right lumbar vein (OR 24.210, 95%CI 2.845-205.998), the maximum diameter of the left lumbar vein (OR 20.973, 95%CI 2.359-186.490), and the length of the tumor thrombus (OR 23.006, 95%CI 2.952-179.309) were independent risk factors for predicting the establishment of inferior vena cava collateral circulation. The AUC of logistic model was 0.969 (95%CI 0.931-1.000). Conclusion:Quantitative parameters of tumor thrombus and lumbar vein based on enhanced MRI have a good ability in predicting the establishment of inferior vena cava collateral circulation in patients with renal cell carcinoma and inferior vena cava tumor thrombus. The maximum diameter of bilateral lumbar veins and the length of the tumor thrombus were independent risk factors for inferior vena cava collateral circulation.

Objective:To investigate the correlations of endoscopic evaluation results with laboratory indices and clinical disease activity in Crohn disease (CD) patients with different intestinal involvement.Methods:Data of 147 patients diagnosed as having CD who visited the Department of Gastroenterology, Zhongnan Hospital of Wuhan University from July 1, 2017 to June 30, 2022 were collected retrospectively. According to the involvement of intestinal segment, patients were divided into three groups: the group with isolated small intestinal involvement ( n=55), the group with both small intestinal and large intestinal involvement ( n=48), and the group with isolated large intestinal involvement ( n=44). Correlations of endoscopic evaluation (based on CDEIS) with laboratory indices and clinical disease activity (based on Harvey-Bradshaw index) were analyzed. Results:C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) could be used for the prediction of endoscopic disease activity. The areas under curve (AUC) of receiver operator characteristic (ROC) were 0.677 (0.506-0.849) and 0.744 (0.597-0.890), respectively. In terms of determing clinical disease activity, clinical Harvey-Bradshaw index was consistent with endoscopic CDEIS score in 65.3% (96/147) patients, showing a low positive correlation ( r=0.260, P<0.05). In subgroup analysis for patients with isolated small intestinal involvement, CRP showed no predictive value for clinical disease activity [AUC (95% CI): 0.617 (0.461-0.773), P=0.148], while for endoscopic activity neither CRP nor ESR showed predictive value [AUC (95% CI): 0.537 (0.146-0.929), P=0.829; AUC (95% CI): 0.571 (0.153-0.990), P=0.680]. Furthermore, for patients with isolated small intestinal involvement and both small intestinal and large intestinal involvement, no correlation was found between clinical Harvey-Bradshaw index and endoscopic CDEIS score ( r=0.222, P=0.092; r=0.142, P=0.322). Conclusion:For CD patients with small intestinal involvement, especially isolated small intestinal involvement, laboratory indices and clinical disease activity cannot accurately reflect endoscopic disease activity. Great importance should be attached to evaluation of the extent and activity of intestinal lesions by endoscopy, especially enteroscopy.