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.

Aromatic traditional Chinese medicine(TCM) has played an important role against epidemics and viruses, and volatile components are the main components that exert the pharmacological effects of aromatic TCM. By screening the related monomer components in aromatic TCM against epidemic and viruses and analyzing and endowing TCM with medicinal properties based on its clinical application and pharmacological research according to the theoretical thinking of TCM, the key technical issues of compatibility of TCM monomer components were solved from a theoretical perspective, providing new ideas and methods for screening raw materials and formulas for the development of new TCM drugs. Based on the conditions of antiviral activity, clinical application foundation, definite therapeutic effect, and high safety, a gradient screening of aromatic TCM was carried out. Firstly, 30 aromatic TCM were screened from anti-epidemic literature and clinical trial formulas, and seven volatile monomers were further screened from them. Then, four monomer components with significant effects, namely patchouli alcohol, carvacrol, p-cymene, and eucalyptol were screened. By adopting the "four-step method for a systematic study of TCM properties", the four monomer components were endowed with medicinal properties, and compatibility and combination studies were conducted to explore the theoretical basis of monomer formulas and form monomer formulas guided by TCM theory. The screening results of volatile monomers in aromatic TCM against viral pneumonia included patchouli alcohol, carvacrol, p-cymene, and eucalyptol. The medicinal properties and compatibility theory of volatile monomer components in TCM were explored. Patchouli alcohol was the main herb, with a cool and pungent nature. It entered the lung meridian to dispel evil Qi and has the effects of aromatization, detoxification, and epidemic prevention. Carvacrol was a minister drug with a cool and pungent taste. It had the effects of aromatizing, moistening, and dissolving the exterior, as well as strengthening the spleen and stomach. p-Cymene was an adjunctive medicine with a mild and pungent nature. It entered the lungs and kidneys and had the effects of aromatic purification, cough relief, and asthma relief. Eucalyptol was also an adjunctive medicine with a pungent and warm taste. It had the functions of aromatic purification, cough relief, phlegm reduction, and pain relief. The combination of the four medicines had the effects of aromatizing, moistening, detoxifying, and epidemic prevention, as well as relieving cough and asthma and strengthening the spleen and stomach. They were used to treat viral pneumonia caused by upper respiratory tract viral infections, with symptoms such as chest tightness, cough, wheezing, fatigue, nasal congestion, runny nose, nausea, and vomiting. This study has laid a literature and theoretical foundation for further drug efficacy verification experiments, compatibility efficacy experiments, and subsequent product development and clinical applications, and it serves as an innovative practice that combines literature research, theoretical research, experimental research, and clinical practice to develop new products.
Drugs, Chinese Herbal/therapeutic use* ; Antiviral Agents/pharmacology* ; Humans ; Pneumonia, Viral/virology* ; Medicine, Chinese Traditional ; Volatile Organic Compounds/pharmacology* ; Animals

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

To enhance the therapeutic efficacy of the baicalin-berberine complex(BA-BBR) in the treatment of ulcerative colitis(UC), BA-BBR nanocrystal microspheres(BA-BBR NC MS) were prepared using the dropping method. The microspheres were characterized in terms of morphology, particle size, differential scanning calorimetry(DSC), and powder X-ray diffraction(XRD). The release profiles of BA and BBR from the microspheres were measured, and the drug release mechanism was investigated. A rat model of UC was induced by 5% dextran sodium sulfate(DSS) and treated continuously for 7 days to evaluate the therapeutic effects of different formulations. The results showed that the prepared BA-BBR MS and BA-BBR NC MS were uniform gel spheres with particle sizes of(1.77±0.16) mm and(1.67±0.08) mm, respectively. After drying, the gels collapsed inward and exhibited a rough surface. During the preparation process, the BA-BBR nanocrystals(BA-BBR NC) were uniformly encapsulated within the microspheres. The release profiles of the microspheres followed a first-order kinetic model, and the 12-hour cumulative release of BA and BBR from BA-BBR NC MS was higher than that from BA-BBR MS. Compared with BA-BBR, BA-BBR NC, and BA-BBR MS, BA-BBR NC MS further alleviated UC symptoms in rats, most significantly reducing the levels of TNF-α, IL-1β, IL-6, and MPO, while increasing the level of IL-4 in colon tissues. These results indicate that BA-BBR NC MS, based on a "nano-in-micro" design, can deliver BA-BBR to the intestine and exert significant therapeutic effects in a UC rat model, suggesting it as a promising new strategy for the treatment of UC.
Animals ; Colitis, Ulcerative/metabolism* ; Rats ; Nanoparticles/chemistry* ; Microspheres ; Male ; Berberine/administration & dosage* ; Flavonoids/administration & dosage* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Particle Size ; Tumor Necrosis Factor-alpha/immunology* ; Drug Liberation ; Drug Compounding

BACKGROUND AND OBJECTIVE: Hypertension (HT) and atrial fibrillation (AF) are highly prevalent cardiovascular conditions that frequently coexist. Coronary artery disease (CAD) is a major global cause of mortality. The co-occurrence of HT, AF, and CAD presents significant management challenges. This study aims to explore the clinical characteristics and risk factors associated with CAD in patients with HT and persistent AF (HT-AF). METHODS: In this retrospective cross-sectional study, data were collected from 384 hospitalized HT-AF patients at the People's Liberation Army General Hospital between January 2010 and December 2019. CAD diagnosis was confirmed by coronary angiography or computed tomography angiography. Clinical characteristics and comorbidities were compared between patients with and without CAD. Multivariate logistic regression analyses were performed to identify independent risk factors associated with CAD development. RESULTS: The prevalence of CAD among HT-AF patients was 66.41% (255/384). Cardiovascular complications, particularly heart failure (44.7% vs 25.6%, P < 0.05), were significantly more prevalent in the CAD group than in the non-CAD group. Only age was identified as an independent risk factor for CAD (adjusted OR: 1.047; 95% CI: 1.022-1.073; P = 0.000). Of all HT-AF patients, 54.7% had a CHA₂DS₂-VASc score of ≥4, indicating high stroke risk. There was a slightly higher anticoagulant usage rate in the CAD group than those without CAD (8.6% vs 4.7%, P = 0.157), and the overall anticoagulant usage remained low. CONCLUSION: There is a high prevalence of CAD among hospitalized HT-AF patients, among whom age is the sole independent risk factor for CAD. Despite a high stroke risk, the utilization of oral anticoagulants is alarmingly low.
Humans ; Atrial Fibrillation/epidemiology* ; Coronary Artery Disease/etiology* ; Hypertension/epidemiology* ; Male ; Female ; Risk Factors ; Middle Aged ; Retrospective Studies ; Cross-Sectional Studies ; Aged ; Prevalence

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

OBJECTIVE To investigate the effects and mechanism of total alkaloids of Corydalis Rhizoma （TAC） on the regulation of cuproptosis in rats with diabetic cardiomyopathy （DCM） based on silence information regulator 1（Sirt1）/tumor protein 53（P53）signaling pathway. METHODS DCM rat model was induced by high-fat and high-sugar diet and intraperitoneal injection of streptozotocin. Thirty-two model rats were randomly divided into model group， TAC low-dose， medium-dose and high-dose groups （7， 10.5， 14 mg/kg）， with 8 rats in each group. An additional 8 rats were assigned to normal control group. Related drugs or normal saline were administered intragastrically in each group， once a day， for 4 weeks. After the last medication， the fasting blood glucose （FBG） levels of the rats were measured. The levels of myocardial creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， and lactate dehydrogenase （LDH） in serum and myocardial tissue of rats were all detected. The pathological morphology， fibrosis degree， and Cu2+ deposition of myocardial tissue in rats were observed. The levels of Cu2+ and glutathione （GSH） in myocardial tissue， the expressions of Sirt1/P53 signaling pathway-related proteins [Sirt1， P53， solute carrier family 7 membrane 11 （SLC7A11）]， and iron-sulfur cluster-related proteins [ferredoxin 1 （FDX1）， lipoic acid synthetase （LIAS）， aconitase 2 （ACO2）， NADH-ubiquinone oxidoreductase core subunit S8 （NDUFS8）， dihydrolipoamide acetyltransferase （DLAT）， dihydrolipoamide succinyltransferase （DLST）]， and heat shock protein 70 （HSP70） were all determined. RESULTS Compared with normal control group， the model group exhibited significantly elevated levels of FBG， CK， CK-MB and LDH in both serum and myocardial tissue， as well as increased 2+ levels of Cu in myocardial tissue and the expression of P53 and HSP70 proteins （P＜0.05）； the level of GSH and the expression levels of Sirt1， SLC7A11， FDX1， LIAS， ACO2， NDUFS8， DLAT， and DLST proteins in myocardial tissue were all significantly decreased （P＜0.05）； the myocardial tissue exhibited severe pathological damage， with numerous inflammatory cell infiltrations and significant fibrosis， as well as increased deposition of Cu2+. Compared with model group， most of the above quantitative indicators in rats were significantly reversed in TAC groups （P＜0.05）； the pathological damage to the myocardial tissue was alleviated， with reduced fibrosis and Cu2+ deposition. CONCLUSIONS TAC can ameliorate DCM in rats， and its mechanism of action may be related to activating the activity of the Sirt1/P53 signaling pathway， promoting the chelation of GSH with Cu2+， and inhibiting cuproptosis of cardiomyocyte.

ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

Objective: To investigate the epidemiological characteristics of pertussis in Jiaxing City from 2004 to 2023 and spatio-temporal clustering characteristics from 2022 to 2023, so as to provide insights into formulation of pertussis control measures. Methods: Data of pertussis cases in Jiaxing City from 2004 to 2023 were collected through the Infectious Disease Report Information System of Chinese Disease Prevention and Control Information System. The epidemiological characteristics of pertussis cases in Jiaxing City from 2004 to 2023 were descriptively analyzed, and the spatio-temporal clustering characteristics from 2022 to 2023 were analyzed using spatio-temporal scanning. Results: A total of 478 pertussis cases were reported in Jiaxing City from 2004 to 2023, with an average annual reported incidence of 0.53/105. The reported incidence showed an upward trend from 2004 to 2023 (P<0.05), with the highest in 2022 (3.17/105). Higher incidence of pertussis was reported in June to August (149 cases, 31.17%) and November to December (112 cases, 23.43%). There was no statistically significant difference in the reported incidence between males and females (0.56/105 vs. 0.50/105, P>0.05). The cases aged under one year accounted for the highest proportion, with 199 cases (41.63%). Haining City (0.68/105), Jiashan County (0.64/105) and Tongxiang City (0.60/105) ranked the top three in the reported incidence of pertussis. Spatio-temporal scanning analysis showed that from 2022 to 2023, the primary clustering area of pertussis was centered in Daqiao Town of Nanhu District, covering 27 towns (streets) in Nanhu District, Jiashan County, Xiuzhou District and Pinghu City, and the clustering time was from November to December, 2023. Conclusions The reported incidence of pertussis was at a low level in Jiaxing City, but showed an upward trend from 2004 to 2023. The incidence of pertussis was higher among infants under one year of age, peaked in June to August and November to December, and was concentrated in Nanhu District and its surrounding areas.

Cold has been a long-term survival challenge in the evolutionary process of mammals. In response to cold stress, in addition to brown adipose tissue (BAT) dissipating energy as heat through glucose and lipid oxidation to maintain body temperature, cold stimulation can strongly activate thermogenesis and energy expenditure in beige fat cells, which are widely distributed in the subcutaneous layer. However, the effects of cold stimulation on other tissues and systemic lipid metabolism remain unclear. Our previous research indicated that, under cold stress, BAT not only produces heat but also secretes numerous exosomes to mediate BAT-liver crosstalk. Whether subcutaneous fat has a similar mechanism is still unknown. Therefore, this study aimed to investigate the alterations in lipid metabolism across various tissues under cold exposure and to explore whether subcutaneous fat regulates systemic glucose and lipid metabolism via exosomes, thereby elucidating the regulatory mechanisms of lipid metabolism homeostasis under physiological stress. RT-qPCR, Western blot, and H&E staining methods were used to investigate the physiological changes in lipid metabolism in the serum, liver, epididymal white adipose tissue, and subcutaneous fat of mice under cold stimulation. The results revealed that cold exposure significantly enhanced the thermogenic activity of subcutaneous adipose tissue and markedly increased exosome secretion. These exosomes were efficiently taken up by hepatocytes, where they profoundly influenced hepatic lipid metabolism, as evidenced by alterations in the expression levels of key genes involved in lipid synthesis and catabolism pathways. This study has unveiled a novel mechanism by which subcutaneous fat regulates lipid metabolism through exosome secretion under cold stimulation, providing new insights into the systemic regulatory role of beige adipocytes under cold stress and offering a theoretical basis for the development of new therapeutic strategies for obesity and metabolic diseases.
Animals ; Lipid Metabolism/physiology* ; Mice ; Exosomes/metabolism* ; Cold Temperature ; Subcutaneous Fat/physiology* ; Thermogenesis/physiology* ; Adipose Tissue, Brown/metabolism* ; Male