Esophageal cancer （EC） is a highly prevalent malignant tumor in China. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， as one of the key oncogenic pathways， can promote the cell cycle progression， proliferation， migration， and invasion， induce chemoresistance， and inhibit apoptosis and autophagy of EC cells. Traditional Chinese medicine （TCM）， with the advantages of targeting multiple points with multiple components to delay cancer progression， can target the PI3K/Akt signaling pathway for EC treatment. This article preliminarily discusses the molecular mechanism and role of the PI3K/Akt signaling pathway in EC and elaborates on the specific targets and efficacy of TCM in treating EC through intervention in the PI3K/Akt signaling pathway in the past five years. TCM materials and extracts inhibiting the PI3K/Akt signaling pathway in EC include Borneolum， spore powder of Ganoderma lucidum without spore coat， extract of Celastrus orbiculatus， root extract of Taraxacum， and Bruceae Fructus oil emulsion. TCM active ingredients exerting the effect include flavonoids， terpenoids， saponins， phenols， polysaccharides， alkaloids， and other compounds. TCM compound prescriptions with such effect include Qige San， Huqi San， Xuanfu Daizhetang， Tongyoutang and its decomposed prescriptions， Liujunzi Tang， and Xishenzhi Formula. In addition， TCM injections such as Compound Kushen Injection and Kang'ai injection also inhibit the PI3K/Akt signaling pathway in EC. This paper summarizes the role of the PI3K/Akt signaling pathway in EC and the TCM interventions， aiming to provide reference for the research and clinical application of new drugs for EC.

ObjectiveTo investigate the association between immunoglobulin G （IgG）/immunoglobulin M （IgM） ratio and prognosis in patients with initially unresectable hepatocellular carcinoma （iuHCC） receiving TTP triple therapy with transcatheter arterial chemoembolization （TACE）， tyrosine kinase inhibitor （TKI）， and programmed cell death protein-1 （PD-1） inhibitors. MethodsA retrospective analysis was performed for the clinical data of 151 iuHCC patients who received TTP triple therapy in Department of Hepatobiliary Surgery， Guangxi Medical University Cancer Hospital， from November 2019 to December 2022， and according to IgG/IgM ratio， they were divided into high IgG/IgM group （IgG/IgM ratio >13.23） and low IgG/IgM group （IgG/IgM ratio ≤13.23）. The t-test was used for comparison of continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method and the log-rank test were used for survival analysis， and the Cox proportional hazards model was used to investigate the potential influencing factors for overall survival （OS）. ResultsThe 151 patients had a median OS of 26.7 months （95% confidence interval ［CI］： 19.8-not reached） and a median progression-free survival of 12.5 months （95%CI： 10.4 — 15.8）. The objective response rate was 83.4% and the disease control rate was 94.0%. There were no significant differences in baseline data between the high IgG/IgM group and the low IgG/IgM group （all P>0.05）. There was a significant difference in median OS between the high IgG/IgM group and the low IgG/IgM group （20.6 months vs not reached， P=0.016）. In both the high IgG/IgM group and the low IgG/IgM group， salvage hepatectomy was significantly associated with the improvement in OS （χ²=8.297 and 10.307， both P<0.05）. The multivariate analysis showed that high IgG/IgM ratio （hazard ratio ［HR］=1.799， 95%CI： 1.077 — 3.006， P=0.025）， baseline alpha-fetoprotein >400 ng/mL （HR=1.762， 95%CI： 1.017 — 3.050， P=0.043）， and BCLC stage （HR=2.265， 95%CI： 1.212 — 4.232， P=0.010） were independent influencing factors for OS. ConclusionHigh IgG/IgM ratio is associated with a poorer prognosis in iuHCC patients receiving TTP triple therapy， and salvage hepatectomy has a potential value in improving the prognosis of patients with a high IgG/IGM ratio.

ObjectiveTo establish a mouse model of particulate matter 2.5 （PM_2.5）-induced dry eye and investigate whether Chufeng Yisuntang can ameliorate the PM_2.5-induced ocular surface damage by regulating the reactive oxygen species （ROS）/p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. MethodsSixty 8-week-old male C57BL/6J mice were used. Ten were randomly selected as the control group. The remaining 50 mice received topical instillation of 1 drop （0.1 mL） of 5 g·L^-1 PM_2.5 suspension in both eyes， four times daily. Successfully modeled mice were randomized into four groups （n=10）： Model， p38 MAPK inhibitor， Chufeng Yisuntang， and combination （Chufeng Yisuntang at 7.3 g·kg^-1 + p38 MAPK inhibitor SB203580 at 5 mg·kg^-1）. Chufeng Yisuntang was administered via gavage， and the inhibitor group via intraperitoneal injection. The control and model groups received equal volumes of distilled water by gavage. All treatments lasted for 4 weeks. General conditions were dynamically observed. Tear secretion， tear film break-up time， and corneal fluorescein staining were assessed. After intervention for 4 weeks， hematoxylin and eosin （HE） staining was used to examine the histopathological changes. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure serum levels of ROS， malondialdehyde （MDA）， superoxide dismutase （SOD） 1， and SOD2. Western blot and Real-time PCR were employed to determine the protein and gene levels， respectively， of p38 MAPK， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and cysteinyl aspartate-specific proteinase-3 （Caspase-3） in the corneal tissue. ResultsCompared with the control group， the model group exhibited reduced tear secretion volume and tear film breakup time， along with increased corneal fluorescein staining scores （P<0.01）. Compared with the model group， the Chufeng Yisuntang group， p38 MAPK inhibitor group， and combination group demonstrated increased tear secretion volume and tear film breakup time， along with decreased corneal fluorescein staining scores （P<0.01）. HE staining revealed that compared with the control group， the model group exhibited marked increases in corneal epithelial cell layers and epithelial thickness， along with reduced meibomian gland acini and intensely stained， densely packed nuclei around the acini. Compared with the model group， the Chufeng Yisuntang group， p38 MAPK inhibitor group， and combination group showed intact corneal structure， improved cell morphology， and reduced damage severity. ELISA revealed elevated ROS and MDA levels （P<0.01） and decreased SOD1 and SOD2 levels （P<0.01） in the model group compared with the control group. Compared with the model group， Chufeng Yisuntang， p38 MAPK inhibitor， and the combination lowered ROS and MDA levels （P<0.01）， while raising SOD1 and SOD2 levels （P<0.05， P<0.01）. Western blot revealed that compared with the control group， the model group exhibited increased protein levels of p38 MAPK， Bax， and Caspase-3 （P<0.01） and reduced protein level of Bcl-2 （P<0.01）. Compared with the model group， Chufeng Yisuntang， p38 MAPK inhibitor， and the combination down-regulated the protein levels of p38 MAPK， Bax， and Caspase-3 （P<0.01）， while up-regulating the protein level of Bcl-2 （P<0.01）. Compared with the Chufeng Yisuntang group， the combination group exhibited decreased protein levels of p38 MAPK， Bax， and Caspase-3 （P<0.01） and increased protein level of Bcl-2 （P<0.01）. Real-time PCR revealed that compared with the control group， the model group exhibited upregulated mRNA levels of p38 MAPK， Bax， and Caspase-3 （P<0.01）， and downregulated mRNA level of Bcl-2 （P<0.01）. Compared with the model group， Chufeng Yisuntang， p38 MAPK inhibitor， and the combination down-regulated the mRNA levels of p38 MAPK， Bax， and Caspase-3 （P<0.01）， while up-regulating the mRNA level of Bcl-2 （P<0.05， P<0.01）. Compared with the Chufeng Yisuntang group， the combination group exhibited decreased mRNA levels of p38 MAPK， Bax， and Caspase-3 expression （P<0.05， P<0.01） and increased mRNA level of Bcl-2 （P<0.01）. ConclusionChufeng Yisuntang may partially protect against PM_2.5-induced corneal injury by inhibiting the ROS/p38 MAPK pathway， enhancing antioxidant defense， and reducing epithelial apoptosis.

Depression is a high-incidence mental disorder with complex causes and multifaceted pathogenic mechanisms. Its pathogenesis has not yet been fully elucidated， which has hindered the development of novel and highly effective antidepressant drugs. This condition severely affects human physical and mental health while imposing a significant socio-economic burden. At present， several hypotheses exist regarding the pathogenesis of depression， including monoamine neurotransmitter imbalances， neurotrophic factor deficiencies， neural plasticity impairments， glutamate dysregulation， neuroinflammatory disorders， gut microbiota imbalances， and mitochondrial autophagy dysfunction. Currently， most clinical antidepressants are monoamine neurotransmitter reuptake inhibitors. Although they exhibit certain therapeutic effects， they are associated with significant drawbacks， such as severe adverse reactions and poor patient compliance. In contrast， traditional Chinese medicine （TCM）， characterized by its multi-targeted effects， mild efficacy， and minimal side effects， has demonstrated significant advantages in the treatment of depression. Chinese medicine Polygalae Radix possesses the functions of calming the mind， enhancing cognitive functions， harmonizing the heart and kidneys， and dispelling phlegm to open orifices. It is often included in compound prescriptions for the clinical treatment of depression. Based on current hypotheses regarding the pathogenesis of depression， this paper systematically reviews research progress on the antidepressant mechanisms of Polygalae Radix from multiple perspectives， including its active components， its use in herbal pairings， and its inclusion in TCM compound prescriptions. This review aims to provide a scientific basis for the clinical application of Polygalae Radix in antidepressant therapy and to serve as a reference for the modernization of its antidepressant research.

Acute burns and chronic wounds frequently fail to heal owing to various reasons. Most drugs currently used for wound therapy in clinical practice have notable drawbacks, making their application a substantial concern. For instance, anti-inflammatory drugs can exert multisystem toxicity, and cellular therapies are costly and difficult to retain. In recent years, natural functional proteins derived from animals and plants have gained increasing attention owing to their unique biological activities, low cost, and broad application prospects in wound therapy. Herein, we isolated a new protein (JH015Y) from amphibians and demonstrated its excellent wound repair and regeneration properties compared with those of epidermal growth factor, both in vitro and in vivo. JH015 protein increased the proliferative ability of human keratinocytes and skin fibroblasts by 47.73 and 41.40%, respectively. In vivo, the medium-dose (0.5 mg/dose) groups of JH015Y protein demonstrated accelerated wound healing from day 4, with wound healing rates 1.26, 1.27, and 1.14 times that of the blank group in acute wounds, burn wounds, and diabetic ulcer, respectively. Histological analysis of Masson-stained sections indicated that the JH015Y protein contributed to collagen deposition on the wound surface, markedly reduced inflammatory cell infiltration, and exhibited low biological toxicity. Accordingly, the JH015Y protein is a promising biotherapeutic agent for accelerated wound repair and regeneration.

The European Society of Cardiology (ESC) released the "2024 ESC guidelines for the management of elevated blood pressure and hypertension" on August 30, 2024. This guideline updates the 2018 "Guidelines for the management of arterial hypertension." One notable update is the introduction of the concept of "elevated blood pressure" (120-139/70-89 mm Hg). Additionally, a new systolic blood pressure target range of 120-129 mm Hg has been proposed for most patients receiving antihypertensive treatment. The guideline also includes numerous additions or revisions in areas such as non-pharmacological interventions and device-based treatments for hypertension. This article interprets the guideline's recommendations on definition and classification of elevated blood pressure and hypertension, and cardiovascular disease risk assessment, diagnosing hypertension and investigating underlying causes, preventing and treating elevated blood pressure and hypertension. We provide a comparison interpretation with the 2018 "Guidelines for the management of arterial hypertension" and the "2017 ACC/AHA guideline on the prevention, detection, evaluation, and management of high blood pressure in adults."

Electroencephalogram (EEG) is a non-invasive, high temporal-resolution technique for monitoring brain activity. However, affected by the volume conduction effect, EEG has a low spatial resolution and is difficult to locate brain neuronal activity precisely. The surface Laplacian (SL) technique obtains the Laplacian EEG (LEEG) by estimating the second-order spatial derivative of the scalp potential. LEEG can reflect the radial current activity under the scalp, with positive values indicating current flow from the brain to the scalp (“source”) and negative values indicating current flow from the scalp to the brain (“sink”). It attenuates signals from volume conduction, effectively improving the spatial resolution of EEG, and is expected to contribute to breakthroughs in neural engineering. This paper provides a systematic overview of the principles and development of SL technology. Currently, there are two implementation paths for SL technology: current source density algorithms (CSD) and concentric ring electrodes (CRE). CSD performs the Laplace transform of the EEG signals acquired by conventional disc electrodes to indirectly estimate the LEEG. It can be mainly classified into local methods, global methods, and realistic Laplacian methods. The global method is the most commonly used approach in CSD, which can achieve more accurate estimation compared with the local method, and it does not require additional imaging equipment compared with the realistic Laplacian method. CRE employs new concentric ring electrodes instead of the traditional disc electrodes, and measures the LEEG directly by differential acquisition of the multi-ring signals. Depending on the structure, it can be divided into bipolar CRE, quasi-bipolar CRE, tripolar CRE, and multi-pole CRE. The tripolar CRE is widely used due to its optimal detection performance. While ensuring the quality of signal acquisition, the complexity of its preamplifier is relatively acceptable. Here, this paper introduces the study of the SL technique in resting rhythms, visual-related potentials, movement-related potentials, and sensorimotor rhythms. These studies demonstrate that SL technology can improve signal quality and enhance signal characteristics, confirming its potential applications in neuroscientific research, disease diagnosis, visual pathway detection, and brain-computer interfaces. CSD is frequently utilized in applications such as neuroscientific research and disease detection, where high-precision estimation of LEEG is required. And CRE tends to be used in brain-computer interfaces, that have stringent requirements for real-time data processing. Finally, this paper summarizes the strengths and weaknesses of SL technology and envisages its future development. SL technology boasts advantages such as reference independence, high spatial resolution, high temporal resolution, enhanced source connectivity analysis, and noise suppression. However, it also has shortcomings that can be further improved. Theoretically, simulation experiments should be conducted to investigate the theoretical characteristics of SL technology. For CSD methods, the algorithm needs to be optimized to improve the precision of LEEG estimation, reduce dependence on the number of channels, and decrease computational complexity and time consumption. For CRE methods, the electrodes need to be designed with appropriate structures and sizes, and the low-noise, high common-mode rejection ratio preamplifier should be developed. We hope that this paper can promote the in-depth research and wide application of SL technology.

Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.

BACKGROUND:Exercise has a regulatory effect on intestinal flora and glucose metabolism,but the effects of high-intensity intermittent exercise on intestinal flora and glucose metabolism in patients with type 2 diabetes mellitus are unclear. OBJECTIVE:To investigate the effects of high-intensity intermittent exercise on glucose metabolism and intestinal flora in patients with type 2 diabetes mellitus. METHODS:Eleven patients with type 2 diabetes mellitus were recruited,among which,two were lost to the follow-up and nine were finally enrolled.High-intensity intermittent exercise intervention was conducted 3 times per week for 6 continuous weeks.Fasting blood and fecal samples were collected before and after the intervention.Glucose metabolism indexes were detected in the blood samples,and intestinal flora was detected in the fecal samples.Changes in glucose metabolism indexes and intestinal flora indexes of the patients with type 2 diabetes mellitus before and after the intervention were compared. RESULTS AND CONCLUSION:After 6 weeks of high-intensity intermittent exercise intervention,fasting blood glucose and glycosylated serum protein levels in patients were significantly reduced(P<0.05),and fasting insulin,although not significantly changed,was decreased compared with before intervention.Alpha diversity analysis showed that the diversity(Shannon index),richness(Chao index)and coverage(Coverage index)did not change significantly.Venn diagrams showed that the relative abundance of Bacteroidetes,Actinobacteria,Proteobacteria,and Fusobacteria in the intestinal flora of the patients increased,and the relative abundance of Firmicutes decreased,and a significant decrease was seen in Ruminococcus_torques and Ruminococcus_gnavus in the Firmicutes,which were both positively correlated with the abnormalities of the glycemic metabolism-related indicators,as well as with other disease development.All these findings indicate that high-intensity intermittent exercise intervention has an improvement effect on the glycemic metabolism-related indexes of patients with type 2 diabetes mellitus,and the abundance of beneficial flora in the intestinal tract increases,and the abundance of harmful flora decreased,enhancing the stability of the intestinal flora in patients.