Central sensitization(CS) is an important factor in inducing neuropathic pain(NPP), and the association between signal transduction protein 1(Epac1) and piezoelectric type mechanosensitive ion channel component 2(Piezo2) is a new and significant pathway for initiating CS. This study whether the central analgesic effect of Maxiong Powder is achieved through the synchronized regulation of the Epac1-Piezo2 signaling pathway in the medial habenular nucleus(MHb) and interpeduncular nucleus(IPN) of the brain. Dynamic in vivo microdialysis, combined with high-performance liquid chromatography-fluorescence detection(HPLC-RFC), behavioral assessments, immunohistochemistry, Western blot, and quantitative reverse transcription PCR, were employed in rats with partial sciatic nerve injury(SNI) to investigate the distribution and expression of Epac1 and Piezo2 proteins and genes in the MHb and IPN regions, and the changes in the extracellular levels of glutamate(Glu), aspartic acid(Asp), and glycine(Gly). Compared with the sham group, rats in the SNI group showed significantly reduced analgesic activity, a significant increase in cold pain sensitivity scores, and elevated Glu levels in the MHb and IPN regions. Additionally, the number of Piezo2-positive cells in these regions, as well as the expression levels of Epac1 and Piezo2 proteins and genes, were significantly increased. Compared with the SNI group, after Maxiong Powder administration, the analgesic activity in rats significantly increased, and cold pain sensitivity scores were significantly reduced. Maxiong Powder also significantly decreased the Glu content in the MHb and IPN regions and the Gly content in the MHb region, while significantly increasing the Asp content in both regions. Furthermore, Maxiong Powder significantly reduced the number of Piezo2-positive cells and lowered the protein and gene expression levels of Epac1 and Piezo2 in both brain regions. The central analgesic effect of Maxiong Powder may be related to its inhibition of Glu and Gly release in the extracellular fluid of the MHb and IPN regions, the increase of Asp levels in these regions, and the regulation of the Epac1-Piezo2 pathway through the reduction of Epac1 and Piezo2 protein and gene expression. These results provide partial scientific evidence for the clinical analgesic efficacy of Maxiong Powder and offer new ideas and approaches for the clinical treatment of NPP.
Animals ; Neuralgia/genetics* ; Rats ; Signal Transduction/drug effects* ; Male ; Rats, Sprague-Dawley ; Guanine Nucleotide Exchange Factors/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Habenula/drug effects* ; Ion Channels/genetics* ; Humans

The study investigated the intrinsic changes in material basis of Angelicae Sinensis Radix during wine processing by headspace-gas chromatography-ion mobility spectrometry(HS-GC-IMS), headspace-solid phase microextraction-gas chromatography-mass spectrometry(HS-SPME-GC-MS), and ultra-high performance liquid chromatography-quadrupole-orbitrap mass spectrometry(UPLC-Q-Orbitrap-MS) combined with chemometrics. HS-GC-IMS fingerprints of Angelicae Sinensis Radix before and after wine processing were established to analyze the variation trends of volatile components and characterize volatile small-molecule substances before and after processing. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were employed for differentiation and difference analysis. A total of 89 volatile components in Angelicae Sinensis Radix were identified by HS-GC-IMS, including 14 unsaturated hydrocarbons, 16 aldehydes, 13 ketones, 9 alcohols, 16 esters, 6 organic acids, and 15 other compounds. HS-SPME-GC-MS detected 118 volatile components, comprising 42 unsaturated hydrocarbons, 11 aromatic compounds, 30 alcohols, 8 alkanes, 6 organic acids, 4 ketones, 7 aldehydes, 5 esters, and 5 other volatile compounds. UPLC-Q-Orbitrap-MS identified 76 non-volatile compounds. PCA revealed distinct clusters of raw and wine-processed Angelicae Sinensis Radix samples across the three detection methods. Both PCA and OPLS-DA effectively discriminated between the two groups, and 145 compounds(VIP>1) were identified as critical markers for evaluating processing quality, including 4-methyl-3-penten-2-one, ethyl 2-methylpentanoate, and 2,4-dimethyl-1,3-dioxolane detected by HS-GC-IMS, angelic acid, β-pinene, and germacrene B detected by HS-SPME-GC-MS, and L-tryptophan, licoricone, and angenomalin detected by UPLC-Q-Orbitrap-MS. In conclusion, the integration of the three detection methods with chemometrics elucidates the differences in the chemical material basis between raw and wine-processed Angelicae Sinensis Radix, providing a scientific foundation for understanding the processing mechanisms and clinical applications of wine-processed Angelicae Sinensis Radix.
Wine/analysis* ; Gas Chromatography-Mass Spectrometry/methods* ; Chromatography, High Pressure Liquid/methods* ; Angelica sinensis/chemistry* ; Solid Phase Microextraction/methods* ; Drugs, Chinese Herbal/isolation & purification* ; Chemometrics ; Volatile Organic Compounds/chemistry* ; Principal Component Analysis ; Ion Mobility Spectrometry/methods*

OBJECTIVE: To explore the early clinical efficacy of a three-stage external treatment with traditional Chinese medicine (TCM) in the treatment of talar bone contusion caused by acute ankle sprain. METHODS: A retrospective analysis was performed on 360 patients with primary lateral ankle sprain admitted from September 2021 to July 2024. Patients with talar bone contusion were selected based on MRI examination, and 73 cases were finally included. According to different treatment methods, they were divided into the observation group and the control group. The observation group consisted of 35 cases, including 16 males and 19 females, aged 24 to 37 years old with an average of (30.34±2.68) years old, and received the three-stage external TCM treatment combined with the "POLICE" protocol. The control group included 38 cases, including 18 males and 20 females, aged 24 to 35 years old with an average of (29.87±2.57) years old, and was treated with the "POLICE" protocol alone. The volume of bone marrow edema (BME) area shown by MRI before treatment and 6 weeks after treatment was measured using 3D Slicer software, and the BME improvement rate was calculated. The "Figure of 8" measurement method was used to assess ankle swelling before treatment and at 1 and 3 weeks after treatment. The visual analogue scale (VAS) was used to evaluate ankle pain before treatment and at 1 and 6 weeks after treatment. At 6 weeks after treatment, the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Karlsson ankle function score system were used to evaluate the improvement of ankle function. RESULTS: A total of 73 patients with talar bone contusion caused by ankle sprain completed the 6-week follow-up. At 6 weeks after treatment, the BME improvement rate in the observation group was (39.18±0.06)%, which was higher than (26.75±0.03)% in the control group, with a statistically significant difference (P<0.05). After 1 week of treatment, the VAS score in the observation group was (2.89±0.72) points, lower than (3.37±0.79) points in the control group, and the difference was statistically significant (P<0.05). The ankle swelling degree in the observation group was (50.20±3.19) cm, lower than (52.00±3.60) cm in the control group, with a statistically significant difference (P<0.05). After 3 weeks of treatment, there was no statistically significant difference in ankle swelling between the two groups. At 6 weeks after treatment, there was no statistically significant difference in VAS scores between the two groups. At 6 weeks after treatment, the AOFAS ankle-hindfoot score and Karlsson score in the observation group were (87.43±4.18) and (82.77±5.93) points, respectively, which were higher than (82.92±4.87) and (76.45±6.85) points in the control group, with statistically significant differences (P<0.05). According to the AOFAS ankle-hindfoot score, 8 cases were excellent and 27 cases were good in the observation group;2 cases were excellent, 33 cases were good, and 3 cases were fair in the control group. The difference between the two groups was statistically significant (χ²=7.089, P=0.029). CONCLUSION The three-stage external TCM treatment combined with the "POLICE" protocol has a significant early clinical efficacy. It can significantly reduce ankle pain and swelling in patients with bone contusion caused by acute lateral ankle sprain, promote the absorption of bone marrow edema, and accelerate the recovery of ankle function.
Ankle Injuries/drug therapy* ; Drugs, Chinese Herbal/administration & dosage* ; Talus/injuries* ; Retrospective Studies ; Administration, Cutaneous ; Magnetic Resonance Imaging ; Humans ; Male ; Female ; Young Adult ; Adult ; Contusions/etiology* ; Visual Analog Scale ; Musculoskeletal Pain/etiology* ; Recovery of Function/drug effects* ; Treatment Outcome ; Follow-Up Studies

Extensive studies have identified potential adverse effects on semen quality of obesity, based on body mass index, but the association between body fat distribution, a more relevant indicator for obesity, and semen quality remains less clear. We conducted a longitudinal study of 4304 sperm donors from the Guangdong Provincial Human Sperm Bank (Guangzhou, China) during 2017-2021. A body composition analyzer was used to measure total and local body fat percentage for each participant. Generalized estimating equations were employed to assess the association between body fat percentage and sperm count, motility, and morphology. We estimated that each 10% increase in total body fat percentage (estimated change [95% confidence interval, 95% CI]) was significantly associated with a 0.18 × 10 6 (0.09 × 10 6 -0.27 × 10 6 ) ml and 12.21 × 10 6 (4.52 × 10 6 -19.91 × 10 6 ) reduction in semen volume and total sperm count, respectively. Categorical analyses and exposure-response curves showed that the association of body fat distribution with semen volume and total sperm count was stronger at higher body fat percentages. In addition, the association still held among normal weight and overweight participants. We observed similar associations for upper limb, trunk, and lower limb body fact distributions. In conclusion, we found that a higher body fat distribution was significantly associated with lower semen quality (especially semen volume) even in men with a normal weight. These findings provide useful clues in exploring body fat as a risk factor for semen quality decline and add to evidence for improving semen quality for those who are expected to conceive.
Humans ; Male ; Adult ; Semen Analysis ; China ; Body Fat Distribution ; Longitudinal Studies ; Sperm Count ; Sperm Motility ; Body Mass Index ; Tissue Donors ; Obesity/complications* ; Spermatozoa ; Young Adult ; Middle Aged ; East Asian People

The intelligent oxygen management system is a software designed with various algorithms to automatically titrate inhaled oxygen concentration according to specific patterns. This system can be integrated into various ventilator devices and used during assisted ventilation processes, aiming to maintain the patient's blood oxygen saturation within a target range. This paper employs a scoping review methodology, focusing on research related to intelligent oxygen management systems in neonatal intensive care units. It reviews the fundamental principles, application platforms, and clinical outcomes of these systems, providing a theoretical basis for clinical implementation.
Humans ; Intensive Care Units, Neonatal ; Infant, Newborn ; Oxygen/administration & dosage* ; Oxygen Inhalation Therapy/methods* ; Respiration, Artificial

BACKGROUND: Our understanding of the correlation between postdischarge cancer and mortality in patients with coronary artery disease (CAD) remains incomplete. The aim of this study was to investigate the relationships between postdischarge cancers and all-cause mortality and cardiovascular mortality in CAD patients. METHODS: In this retrospective cohort study, 25% of CAD patients without prior cancer history who underwent coronary artery angiography between January 1, 2011 and December 31, 2015, were randomly enrolled using SPSS 26.0. Patients were monitored for the incidence of postdischarge cancer, which was defined as cancer diagnosed after the index hospitalization, survival status and cause of death. Cox regression analysis was used to explore the association between postdischarge cancer and all-cause mortality and cardiovascular mortality in CAD patients. RESULTS: A total of 4085 patients were included in the final analysis. During a median follow-up period of 8 years, 174 patients (4.3%) developed postdischarge cancer, and 343 patients (8.4%) died. A total of 173 patients died from cardiovascular diseases. Postdischarge cancer was associated with increased all-cause mortality risk (HR = 2.653, 95% CI: 1.727-4.076, P < 0.001) and cardiovascular mortality risk (HR = 2.756, 95% CI: 1.470-5.167, P = 0.002). Postdischarge lung cancer (HR = 5.497, 95% CI: 2.922-10.343, P < 0.001) and gastrointestinal cancer (HR = 1.984, 95% CI: 1.049-3.750, P = 0.035) were associated with all-cause mortality in CAD patients. Postdischarge lung cancer was significantly associated with cardiovascular death in CAD patients (HR = 4.979, 95% CI: 2.114-11.728, P < 0.001), and cardiovascular death was not significantly correlated with gastrointestinal cancer or other types of cancer. CONCLUSIONS Postdischarge cancer was associated with all-cause mortality and cardiovascular mortality in CAD patients. Compared with other cancers, postdischarge lung cancer had a more significant effect on all-cause mortality and cardiovascular mortality in CAD patients.

Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO₂ bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-β1 (TGF-β1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.

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*