This study elucidates the mechanism of Rhodiolae Crenulatae Radix et Rhizoma(RCRR) in protecting brain microvascular endothelial cells from oxygen-glucose deprivation(OGD) injury and reveals the modern pharmacological mechanism of RCRR's traditional use in nourishing Qi and promoting blood circulation to protect endothelial cells. The scratch assay was employed to assess the migratory capacity of endothelial cells. Immunofluorescence and Western blot techniques were employed to assess the protein expression of tight junction proteins zonula occludens-1(ZO-1), occludin, claudin-5, and proteins of the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/glycogen synthase kinase-3beta(GSK3β) pathway. The results demonstrated that 63 bioactive components and 125 potential core targets of RCRR were identified from the ETCM, TCMBank, and SwissTargetPrediction databases, as well as from the literature. A total of 1 708 brain microvascular endothelial cell-related targets were identified from the GeneCards and OMIM databases, and 52 targets were obtained by intersecting drug components with cell targets. The protein-protein interaction(PPI) network analysis revealed that AKT1, epidermal growth factor receptor(EGFR), matrix metalloproteinase 9(MMP9), estrogen receptor 1(ESR1), proto-oncogene tyrosine-protein kinase(SRC), peroxisome proliferator-activated receptor gamma(PPARG), GSK3β, and matrix metalloproteinase 2(MMP2) were considered hub genes. The KEGG enrichment analysis identified the PI3K/AKT pathway as the primary signaling pathway. Cell experiments demonstrated that RCRR-containing serum could enhance the migratory capacity of brain microvascular endothelial cells and the expression of tight junction proteins following OGD injury, which may be associated with the downregulation of the PI3K/AKT/GSK3β pathway. This study elucidates the pharmacological mechanism of RCRR in protecting brain microvascular endothelial cells through network pharmacology, characterized by multiple components and targets. These findings were validated through in vitro experiments and provide important ideas and references for further research into the molecular mechanisms of RCRR in protecting brain microvascular endothelial cells.
Endothelial Cells/cytology* ; Glycogen Synthase Kinase 3 beta/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Phosphatidylinositol 3-Kinases/genetics* ; Signal Transduction/drug effects* ; Brain/metabolism* ; Humans ; Animals ; Rhizome/chemistry* ; Microvessels/metabolism* ; Brain Ischemia/drug therapy*

This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

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 analyze the disease burden of chronic kidney diseases (CKD) attributed to high body mass index (BMI) in China from 1992 to 2021 and predict the disease burden for the next decade, and to provide evidence for the prevention and treatment of CKD. Methods Using the Global Burden of Disease (GBD) database and the Joinpoint model, the average annual percentage rate change (AAPC) of the mortality rate and disability-adjusted life year (DALY) rate was calculated to describe and analyze the CKD disease burden attributed to high BMI in China from 1992 to 2021. The ARIMA model was employed to predict and analyze the change trend of the CKD disease burden. Results From 1992 to 2021, the mortality rate and DALY rate attributed to high BMI-induced chronic kidney disease showed an upward trend. Compared to 1992, the attributed number of deaths increased by 324.38%, and DALYs increased by 268.56%; the mortality rate increased by 64.00%, and the DALY rate grew by 51.62%. From 1992 to 2021, the mortality rate and DALY rate for males were lower than those for females, but the growth rate for males exceeded that of females. From 1992 to 2021, the mortality rate and DALY rate of chronic kidney disease attributed to high BMI in China increased with age. The average annual change rate of chronic kidney disease attributed to high BMI in China from 1992 to 2021 (mortality rate: 1.40 per 100,000 (95% CI: 1.04–1.76), DALY rate: 1.43 per 100 000 (95% CI: 1.17–1.70)) was higher than thHuaiyin Normal University, Huai'anher social demographic index (SDI) regions. The ARIMA model predicted that the age-standardized mortality rate increased from 2.91 per 100 000 in 2022 to 3.05 per 100 000 in 2026, and the age-standardized DALY rate increased from 69.65 per 100 000 in 2022 to 73.58 per 100 000 in 2026. Conclusion Chronic kidney disease attributed to high BMI in China is on the rise, and it will continue to grow in the future. The focus of CKD prevention and control should be on males and the elderly, while active measures should be taken to reduce the occurrence and progression of chronic kidney disease.

OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard treatment regimen in the treatment of diabetic nephropathy （DN）. METHODS From the perspective of healthcare service providers， a Markov model was established to simulate the dynamic changes of each stage in DN patients who received finerenone combined with the standard treatment regimen or the standard treatment regimen alone based on the phase Ⅲ clinical trial study of finerenone for DN. Markov model was used to perform the cost-effectiveness of long-term effects and the costs of the two therapies with a simulation cycle of 4 months， a simulation period of 15 years and an annual discount rate of 5%. At the same time， one-way sensitivity analysis and probability sensitivity analysis were performed， and the stability of the results was validated. RESULTS Accumulative cost of the standard treatment regimen was 579 329.54 yuan， and the accumulative utility was 8.052 4 quality-adjusted life year （QALYs）； the accumulative cost of finerenone combined with the standard treatment regimen was 332 520.61 yuan， and the accumulative utility was 8.187 4 QALYs. Finerenone combined with the standard treatment regimen was more cost-effective. The results of one-way sensitivity analysis showed that dialysis status utility value， DN stage 3 utility value and DN stage 4 utility value had a great influence on the incremental cost-effectiveness ratio， but did not affect the robustness of the model. The results of probability sensitivity analysis showed that finerenone combined with the standard treatment regimen was more cost-effective with 100% probability. CONCLUSIONS For DN patients， finerenone combined with the standard treatment regimen is more cost-effective as an absolute advantage option.

With the rapid development of sequencing technologies, the detection of alternative polyadenylation (APA) in mammals has become more precise. APA precisely regulates gene expression by altering the length and position of the poly(A) tail, and is involved in various biological processes such as disease occurrence and embryonic development. The research on APA in mammals mainly focuses on the following aspects:(1) identifying APA based on transcriptome data and elucidating their characteristics; (2) investigating the relationship between APA and gene expression regulation to reveal its important role in life regulation;(3) exploring the intrinsic connections between APA and disease occurrence, embryonic development, differentiation, and other life processes to provide new perspectives and methods for disease diagnosis and treatment, as well as uncovering embryonic development regulatory mechanisms. In this review, the classification, mechanisms and functions of APA were elaborated in detail and the methods for APA identifying and APA data resources based on various transcriptome data were systematically summarized. Moreover, we epitomized and provided an outlook on research on APA, emphasizing the role of sequencing technologies in driving studies on APA in mammals. In the future, with the further development of sequencing technology, the regulatory mechanisms of APA in mammals will become clearer.

Objective: To investigate treatment strategies for chronic periapical periodontitis in prematurely erupted premolars and provide guidance for managing pulp and periapical diseases in young permanent teeth with immature roots. Methods: A regenerative endodontic procedure (REP) was performed on a prematurely erupted maxillary left first premolar (tooth 24) at Nolla stage Ⅶ with chronic apical periodontitis, following standardized protocols including root canal irrigation, disinfection, and coronal sealing. The case was followed up, and a literature review was conducted. Results: Clinical resolution of symptoms was observed on tooth 24, with sustained root development. After a 20-month follow-up, the tooth had restored biological function. Literature synthesis revealed that periapical infections in prematurely erupted permanent teeth predominently arise from pulp exposure and bacterial infection, with retrograde infection being rare. For young permanent teeth with necrotic pulp, regenerative endodontic procedures has been established as the treatment of choice to promote apical closure and root maturation. The critical steps of regenerative endodontic procedures include thorough disinfection, induced bleeding to form a fibrin scaffold, and coronal sealing to facilitate stem cell recruitment and differentiation. Conclusion Regenerative endodontic procedures represents an effective and viable treatment option for prematurely erupted young permanent teeth with chronic periapical periodontitis.

Objective: To explore the independent effects and gender differences of different types of adverse childhood experiences (ACEs) on the co-occurrence of non-suicidal self-injury (NSSI) and suicide attempts (SA), so as to provide a reference for the precise prevention and control of self-harm in junior high school students. Methods: From May to June 2023, a total of 7 360 junior high school students were selected from 12 schools in three districts/counties of Chongqing using a combination of stratified cluster sampling and convenience sampling methods. Information on NSSI, SA, ACEs, and depressive symptom, as well as other related data were collected through the Adolescent Non-suicidal Self-injury Assessment Questionnaire (ANSAQ), suicide related section of the Chinese Adolescent Health related Behavior Questionnaire (Junior High School Version), Childhood Trauma Questionnaire-Short Form ( CTQ- SF), and Center for Epidemiologic Studies-Depression Scale (CES-D). Statistical analyses of the data were performed using the Chi-square test and multiple Logistic regression. Results: The detection rates of NSSI, SA, NSSI+SA and ACEs in junior high school students were 19.2%, 4.6%, 3.5% and 57.9% respectively. After controlling for factors such as gender, grade, family type, self rated family economic status, self rated academic performance, self rated academic pressure, number of close friends, and depressive symptom scores, results from the multiple Logistic regression analysis showed that junior high school students with physical abuse ( OR = 1.98, 95% CI =1.23-3.18), emotional abuse ( OR =2.83, 95% CI =1.92-4.19), sexual abuse ( OR = 1.70, 95% CI =1.07- 2.69 ), physical neglect ( OR =1.67, 95% CI =1.20-2.33) and witnessing domestic violence ( OR =2.10, 95% CI =1.41-2.87) in childhood had higher risks for the occurrence of NSSI+SA (all P <0.05). After stratification by gender, boys with sexual abuse in childhood had a high risk for the occurrence of NSSI+SA ( OR =2.17, 95% CI =1.06-4.43), whereas girls with emotional abuse ( OR =3.69, 95% CI =2.29-5.94), physical neglect ( OR =1.62, 95% CI =1.07-2.45) and witnessing domestic violence ( OR =2.17, 95% CI =1.41-3.34) in childhood had hgih risks for the occurrence of NSSI+SA (all P <0.05). Conclusions Different types of ACEs have different effects on the co-occurrence of self-harm in junior high school students and there are gender differences. When family interventions are conducted for the combined model, emphasis should be placed on aspects of emotional abuse and domestic violence while optimizing the interventions based on gender differences.