Healthy dental pulp is essential for preserving teeth and maintaining their normal function. Vital pulp therapy (VPT) is widely used in clinical applications because it aims to preserve vital pulp and enhance the long-term survival of teeth. An accurate diagnosis of pulp vitality is a prerequisite for successful VPT. However, accurately assessing pulp viability remains challenging in clinical practice. Pulp viability is influenced by various factors, including the type of pulp exposure, caries status, periodontitis, trauma, treatment factors, patient age, and individual differences. Assessing pulp viability requires a comprehensive consideration of medical history and clinical manifestations, along with a combination of various auxiliary methods, such as pulp sensibility tests, pulp blood flow tests, imaging techniques and molecular diagnostics. In the future, the technology for assessing pulp vitality should evolve toward chairside, visualization, and precision techniques, to achieve consistency between clinical and histological diagnoses, thereby providing patients with the most effective treatment.

Serotonin-selective reuptake inhibitors （SSRIs）， as widely used antidepressants in clinical practice， exhibit significant individual differences in antidepressant efficacy. Gut microbiota plays an important role in the development and progression of depression， and the use of SSRIs exerts a significant impact on the gut microbiota of patients with depression. Based on this， this article reviews the research progress on the interactions between the antidepressant effects of SSRIs and gut microbiota. It has been found that SSRIs can influence the diversity， abundance， and function of the gut microbiota directly or indirectly. Conversely， the composition of the gut microbiota and differences in its functional metabolic pathways， and other factors， can in turn affect the antidepressant effects of SSRIs. Therefore， in clinical practice， gut microbiota diversity can be utilized as a predictive indicator for the antidepressant effects of SSRIs. Probiotics can be employed as an adjunct therapy alongside SSRIs， and dietary adjustments， as well as fecal microbiota transplantation， can be used to enhance the therapeutic efficacy of SSRIs. In the future， large-scale， multicenter clinical studies should be conducted， enrolling a broadly representative cohort of patients with depression， to uncover the true association between the antidepressant effects of SSRIs and gut microbiota， thereby opening up more effective avenues for the comprehensive treatment of depression.

PURPOSE: To investigate the incidence and influencing factors of bone loss in patients with spinal cord injury (SCI). METHODS: A retrospective case-control study was conducted. Patients with SCI in our hospital from January 2019 to March 2023 were collected. According to the correlation between bone mineral density (BMD) at different sites, the patients were divided into the lumbar spine group and the hip joint group. According to the BMD value, the patients were divided into the normal bone mass group (t > -1.0 standard deviation) and the osteopenia group (t ≤ -1.0 standard deviation). The influencing factors accumulated as follows: gender, age, height, weight, cause of injury, injury segment, injury degree, time after injury, start time of rehabilitation, motor score, sensory score, spasticity, serum value of alkaline phosphatase, calcium, and phosphorus. The trend chart was drawn and the influencing factors were analyzed. SPSS 26.0 was used for statistical analysis. Correlation analysis was used to test the correlation between the BMD values of the lumbar spine and bilateral hips. Binary logistic regression analysis was used to explore the influencing factors of osteoporosis after SCI. p < 0.05 was considered statistically significant. RESULTS: The incidence of bone loss in patients with SCI was 66.3%. There was a low concordance between bone loss in the lumbar spine and the hip, and the hip was particularly susceptible to bone loss after SCI, with an upward trend in incidence (36% - 82%). In this study, patients with SCI were divided into the lumbar spine group (n = 100) and the hip group (n = 185) according to the BMD values of different sites. Then, the lumbar spine group was divided into the normal bone mass group (n = 53) and the osteopenia group (n = 47); the hip joint group was divided into the normal bone mass group (n = 83) and the osteopenia group (n = 102). Of these, lumbar bone loss after SCI is correlated with gender and weight (p = 0.032 and < 0.001, respectively), and hip bone loss is correlated with gender, height, weight, and time since injury (p < 0.001, p = 0.015, 0.009, and 0.012, respectively). CONCLUSIONS The incidence of bone loss after SCI was high, especially in the hip. The incidence and influencing factors of bone loss in the lumbar spine and hip were different. Patients with SCI who are male, low height, lightweight, and long time after injury were more likely to have bone loss.
Humans ; Spinal Cord Injuries/complications* ; Male ; Female ; Retrospective Studies ; Incidence ; Adult ; Bone Density ; Middle Aged ; Case-Control Studies ; Osteoporosis/etiology* ; Lumbar Vertebrae ; Bone Diseases, Metabolic/etiology* ; Aged ; Risk Factors

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

In the context of delayed marriage and parenthood, decreased willingness in having children, and population aging in China, maternal and child health has become an important and urgent issue. Being essential platforms for research in maternal and child health, the importance of birth cohorts has been widely recognized. In the past 20 years, tens of birth cohorts have been established in major cities and regions of China, with cohorts ranging from thousands to hundreds of thousands. These cohorts, particularly those large ones launched in recent years, have collected a wide spectrum of data and biological samples from mothers and children. Although they have made considerable preliminary achievements, there remain difficulties and challenges. The significant challenges include small and medium-sized cohorts' lacking of clear research themes; insufficient recognition of and emphasis on behavioral and social determinants of health while emphasizing biological determinants of health; variations in types of variables and quality of data collected, which make it difficult for cohorts to be merged and shared; lack of and difficulties in long-term follow-up; significant uncertainties in resources for long-term sustention of the cohorts, and so on. So, we argue that birth cohorts should focus on essential and urgent issues in maternal and child health in the country and seek recognition and support from the government and the entire society. Last but not least, the overall success of birth cohorts in the country requires scientists to be not only academically capable, but also realistic, persistent, altruistic, and collaborative.

Elemene, derived from Curcuma wenyujin, one of the "8 famous genuine medicinal materials of Zhejiang province," exhibits remarkable antitumor activity. It has gained wide recognition in clinical practice for effectiveness on tumors. Dr. XIE Tian, introduced the innovative concept of "molecular compatibility theory" by combining Chinese medicine principles, specifically the "monarch, minister, assistant, and envoy" theory, with modern biomedical technology. This groundbreaking approach, along with a systematic analysis of Chinese medicine and modern biomedical knowledge, led to the development of elemene nanoliposome formulations. These novel formulations offer numerous advantages, including low toxicity, well-defined composition, synergistic effects on multiple targets, and excellent biocompatibility. Following the principles of the "molecular compatibility theory", further exploration of cancer treatment strategies and methods based on elemene was undertaken. This comprehensive review consolidates the current understanding of elemene's potential antitumor mechanisms, recent clinical investigations, advancements in drug delivery systems, and structural modifications. The ultimate goal of this review is to establish a solid theoretical foundation for researchers, empowering them to develop more effective antitumor drugs based on the principles of "molecular compatibility theory".
Humans ; Retrospective Studies ; Antineoplastic Agents/therapeutic use* ; Neoplasms/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Sesquiterpenes/therapeutic use*

Intermittent theta burst stimulation (iTBS), a time-saving and cost-effective repetitive transcranial magnetic stimulation regime, has been shown to improve cognition in patients with Alzheimer's disease (AD). However, the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown. Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation. Here, we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1 (ISCA1, an essential regulatory factor for mitochondrial respiration) in the brain of APP/PS1 mice. In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function, which is required for ISCA1. Moreover, iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice. The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD. We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.
Humans ; Mice ; Animals ; Transcranial Magnetic Stimulation ; Alzheimer Disease/therapy* ; Cognitive Dysfunction/therapy* ; Cognition ; Sulfur ; Iron ; Iron-Sulfur Proteins ; Mitochondrial Proteins

OBJECTIVE To explore the effect of volatile oil of Ligusticum chuanxiong on the transdermal properties and cytotoxicity of triptolide in vitro. METHODS The chemical constituents of the volatile oil of L. chuanxiong were analyzed by gas chromatography-mass spectrometry. The lower abdominal skin of KM mice was separated and divided into triptolide group， triptolide in compatibility with volatile oil of L. chuanxiong groups at 1∶10， 1∶50， 1∶100 （hereinafter referred to as “compatibility 1∶10”“compatibility 1∶50”“compatibility 1∶100” groups）. After the skin of mice in each group was fully exposed to 0.2 g of the corresponding cream for 24 h， the cumulative transdermal dose （Qn） of triptolide in the receiving solution of each group was determined by high-performance liquid chromatography， and the transdermal absorption rate （Jss） was calculated. Human immortalized keratinocytes （HaCat） were used as a model， the CCK-8 method was used to detect the cell survival rate of different concentrations of the volatile oil of L. chuanxiong and triptolide before and after compatibility. RESULTS A total of 62 chemical constituents of the volatile oil of L. chuanxiong were identified， including Z-ligustilide， senkyunolide， and β-selinene. The Qn （P＜ 0.01） and Jss of triptolide increased within 24 h in the compatibility 1∶10 and 1∶50 groups， while the Qn （P＜0.05） and Jss decreased in the compatibility 1∶100 group as compared with the triptolide group. Compared with the triptolide group， the cell survival rate of HaCat was significantly increased in the compatibility 1∶10 and 1∶50 groups when the triptolide concentrations were 36， 72 and 144 ng/mL （P＜0.05 or P＜0.01）； while the cell survival rate of HaCat was decreased in the compatibility 1∶100 group， but the difference was not statistically significant （P＞0.05）. CONCLUSIONS When the compatibility ratio of triptolide and volatile oil of L. chuanxiong was 1∶10 or 1∶50， it can promote the transdermal absorption of triptolide and reduce the cytotoxicity of triptolide to HaCat.

Objective: To examine the association of hypertension onset age with diabetes, so as to provide insights into reducing the the risk of cardiovascular events. Methods: Permanent residents aged 35 to 75 years were selected through the program of early screening and comprehensive intervention for the high-risk cardiovascular disease population in Changning District and Baoshan District, Shanghai Municipality from 2016 to 2020. Demographic information, disease history, hypertension onset age, blood pressure and fasting blood glucose were collected through questionnaire surveys, physical examination and laboratory tests. The residents were divided into four groups based on the onset age of hypertension: <45, 45-<55, 55-<65 and ≥65 years old, and the residents with normal blood pressure were selected as control. The association of hypertension onset age with prediabetes and diabetes were identified using a multivariable logistic regression model. Results: A total of 25 228 residents were recruited, including 8 753 males (34.70%) and 16 475 females (65.30%). The prevalence of hypertension was 43.80%. There were 1 779, 3 274, 3 781 and 2 217 cases with hypertension onset age of <45, 45-<55, 55-<65 and ≥65 years old, respectively, and 14 177 residents with normal blood pressure. The prevalence of prediabetes and diabetes were 24.01% and 11.29%, respectively. Multivariable logistic regression analysis showed that after adjusting for confounding factors such as gender, marital status and educational level, compared with the normal blood pressure group, the risk of prediabetes was higher in the hypertension onset age groups of <45 (OR=1.345, 95%CI: 1.164-1.553), 45-<55 (OR=1.365, 95%CI: 1.212-1.536) and 55-<65 years old (OR=1.376, 95%CI: 1.239-1.527), and the risk of diabetes was higher in the hypertension onset age groups of <45 (OR=2.302, 95%CI: 1.906-2.775), 45-<55 (OR=2.349, 95%CI: 2.016-2.734), 55-<65 (OR=1.909, 95%CI: 1.667-2.184) and ≥65 years old (OR=1.315, 95%CI: 1.131-1.526). Conclusion There are statistically significant associations between hypertension onset age with prediabetes and diabetes.