OBJECTIVE To investigate the effect of Huangqin decoction （HQD）-based self-assembled nanoparticles （SAN） co-loaded with terbinafine （TBF） （TBF-HQD-SAN NPs） on the transdermal absorption of TBF. METHODS High-speed centrifugation combined with dialysis was used to separate HQD-SAN， and TBF-HQD-SAN NPs were obtained by loading TBF using the ultrasound magnetic stirring method； the particle size distribution， Zeta potential and polydispersity index （PDI） of the nanoparticle were characterized， and the encapsulation efficiency （EE） and drug loading （DL） of TBF were determined； using in vitro and in vivo transdermal experiments， the differences in transdermal performance between TBF-HQD-SAN NPs and TBF raw materials， as well as TBF and HQD-SAN physical mixture （TBF-HQD-SAN PM）， were compared and analyzed. RESULTS TBF- HQD-SAN NPs were spherical with a particle size of （177.60±2.57） nm， a PDI of 0.197 4±0.007 9， and a Zeta potential of （－14.63±0.85） mV. The EE and DL of TBF were （99.49±0.71）% and （3.22±0.10）% ， respectively. In vitro transdermal experiments， compared with TBF raw materials， the steady-state permeation rate （Jss） and skin retention of TBF-HQD-SAN NPs increased by 3.34 times and 27.56 times， respectively （P＜0.05）； compared with TBF-HQD-SAN PM， its Jss and skinretention were increased by 2.04 times and 7.44 times， respectively （P＜0.05）. In vivo transdermal experiments 69号） showed that， the area under the drug-time curve and the maximum concentration of TBF-HQD-SAN NPs increased by 2.13 times and 2.06 times respectively compared to TBF raw materials， and increased by 1.59 times and 1.65 times respectively compared to TBF-HQD-SAN PM （P＜0.05）. CONCLUSIONS TBF-HQD-SAN NPs can significantly enhance the in vitro and in vivo transdermal absorption efficiency and skin retention of TBF.

To investigate the clinical efficacy of neoadjuvant imatinib in the treatment of rectal gastrointestinal stromal tumor (GIST).

OBJECTIVE To observe the clinical efficacy of mycophenolate mofetil （MMF） combined with Budesonide enteric capsules in the treatment of high-risk progressive immunoglobulin A nephropathy （IgAN）. METHODS A total of 150 adult patients with high-risk progressive IgAN who attended the Department of Nephrology， Chongqing University Three Gorges Hospital， between August 1， 2024 and March 1， 2025 were enrolled in this study. The control group （ n ＝94） received MMF combined with glucocorticoid， while the observation group （ n ＝56） received MMF combined with Budesonide enteric capsules. The 24-hour urine protein （24 h UP）， estimated glomerular filtration rate （eGFR）， and albumin （ALB） levels of patients in both groups were compared at 1， 2， 3， and 6 months post-treatment. The complete response （CR） rate and overall response rate were calculated for both groups at 1， 2， 3， and 6 months post-treatment. Adverse reactions occurring during treatment were compared between the two groups. RESULTS Compared with before treatment， 24 h UP decreased significantly in both groups at different time points after treatment （ P ＜0.05）， and ALB increased significantly （ P ＜0.05）. However， there was no significant change in eGFR （ P ＞0.05）. The 24 h UP in the observation group at 1， 2， and 3 months after treatment was significantly lower than that of the control group （ P ＜0.05）， while the ALB level was significan tly higher （ P ＜0.05）. However， at 6 months after treatment， there was no statistically significant difference in these two indicators between the two groups （ P ＞0.05）. There was no statistically significant difference in eGFR between the two groups at different time points after treatment （ P ＞0.05）. The overall response rates in the observation group at 1 and 2 months after treatment were significantly higher than those in the control group （ P ＜0.05）. There was no statistically significant difference in the overall response rate at the remaining treatment time points and the CR rate at all time points between the two groups （ P ＞0.05）. Patients in the observation group had significantly lower rates of skin abnormalities， elevated blood glucose， and overall adverse reactions compared with the control group （ P ＜0.05）. CONCLUSIONS Compared with MMF combined with glucocorticoids， MMF combined with Budesonide enteric capsules for the treatment of high-risk progressive IgAN patients can reduce proteinuria and improve serum ALB levels more quickly， significantly increase the early overall response rate， and significantly reduce glucocorticoid-related skin adverse reactions， blood glucose elevation， and the overall incidence of adverse reactions， demonstrating a better short-term benefits.

Objective To evaluate the safety and efficacy of a self-developed micro-normothermic machine perfusion (NMP) system (micro-perfusion device) for preserving isolated porcine limbs. Methods Five healthy Landrace pigs were selected, and their left and right forelimbs were randomly divided into the NMP group and static cold storage (SCS) group. The NMP group was perfused with the self-developed micro-perfusion device and polymerized hemoglobin perfusate for 32 hours at normothermia, while the SCS group was preserved at 4 ℃. Hemodynamic parameters such as perfusion pressure and flow were monitored. The pH value, partial pressure of oxygen (PO₂), lactic acid (Lac), creatine kinase (CK) and lactate dehydrogenase (LDH) in the perfusate were measured. Hematoxylin-eosin staining was used to assess the muscle tissue structure, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was employed to evaluate muscle cell apoptosis, and immunohistochemistry staining was applied to detect the expressions of tumor necrosis factor (TNF)-α and interleukin (IL)-6. A mixed-effects model was used to analyze the effects of time and treatment methods on tissue structure, cell apoptosis and inflammatory factors. Results The device could stably maintain a perfusion pressure of (69±15) mmHg and a flow rate of (117±42) mL/min. The pH value and electrolytes of the perfusate were generally stable, with PO₂ maintained at a high level. Lac was maintained at 5.38(3.81, 6.45) mmol/L, while CK and LDH increased over time. After 32 hours of perfusion in the NMP group, both the myocyte spacing and apoptosis rate were better than those in the SCS group. Mixed-effects model analysis showed that there were statistically significant differences in the effects of NMP treatment and SCS treatment on myocyte spacing and apoptosis rate per unit time (both P < 0.05). There were no statistically significant differences in TNF-α and IL-6 between the two groups, and mixed-effects model analysis showed no statistically significant differences in the effects of NMP treatment and SCS treatment on TNF-α and IL-6 per unit time (both P > 0.05). Conclusions The micro-perfusion device used in this study may achieve 32-hour normothermic preservation in a porcine limb amputation model, maintain basic metabolism and ionic homeostasis, reduce muscle structural damage and cell apoptosis without inducing additional inflammatory responses. This technology is expected to significantly extend the time window for replantation of amputated limbs in disaster rescue and long-distance transportation, providing an important technical basis for clinical translation and subsequent replantation research.

Although global brain science research has progressed rapidly in recent decades, several fundamental questions in neuroscience remain unresolved. In particular, the physical mechanism underlying neural signal transmission remains controversial, and the carriers responsible for neural information storage and retrieval have not yet been fully clarified. These unresolved issues motivate us to re-examine the processes of neural information generation, transmission, integration, storage, and retrieval from multiple perspectives. A key observation is that neural electromagnetic activities are closely associated with time. Their duration, temporal structure, and dynamic evolution play crucial roles in neural information processing. In this work, we analyze neural electromagnetic activities from the perspective of temporal scales (referred to here as the “time course”). By reviewing and integrating findings from previous studies, we examine the characteristic time requirements and dynamic features of neural processes occurring at different stages of information processing. These stages include neural signal generation, signal transmission along axons, synaptic integration, synaptic plasticity, and memory formation and retrieval. Based on this temporal analysis, we outline a framework describing neural electromagnetic activities across a wide range of time scales, spanning from microseconds to minutes, hours, or even longer periods associated with long-term memory, which suggests that neural information processing involves multiple physical processes operating at different time levels. Rapid electromagnetic events may occur on microsecond scales, whereas electrophysiological phenomena such as action potentials typically last on the order of milliseconds. Longer time scales are associated with synaptic plasticity and memory-related processes. From this perspective, we propose that the physical carrier of neural information may be transient electromagnetic pulses with durations on the microsecond scale. In this framework, action potentials can be interpreted as the macroscopic electrophysiological manifestation of underlying electromagnetic processes triggered by ionic currents across neuronal membranes. Rather than being the fundamental neural signal itself, the action potential may represent a measurable membrane-level response associated with the successful activation of these electromagnetic events. Moreover, we discuss a possible mechanism for long-term memory storage. Considering the apparent temporal contradiction between the millisecond-scale excitation of neurons and the long-term persistence of memories, we believe that long-term memory information may be stored within neural network topologies formed by electrical synapse coupling. Such structures, referred to as electrically coupled memory networks (ECMNs), may enable neurons within the same network to respond rapidly and synchronously to stimuli, thereby facilitating efficient memory retrieval. Overall, this study emphasizes the importance of considering the temporal organization of neural electromagnetic activities when interpreting neural signaling mechanisms. It may provide new insights into the physical nature of neural information carriers and the mechanisms of memory storage and retrieval. Furthermore, highlighting the potential role of electromagnetic interactions in neural activity may contribute to the development of new theoretical frameworks and experimental approaches in neuroscience. Such perspectives may also offer valuable references for future research on neural coding, brain function mechanisms, and neuromodulation technologies.

Xuefu zhuyu decoction is a classic formula for promoting blood circulation and resolving blood stasis， characterised by its remarkable ability to treat different diseases with the same approach. Qi stagnation and blood stasis， the primary syndrome for which this formula is indicated， has been found through modern medical research to be intrinsically linked to a wide range of pathophysiological processes， including microcirculatory disorders， abnormalities in hemorheology， inflammatory responses and endothelial dysfunction； which opens up vast scope for the innovative application of traditional formulas. In terms of pharmacological effect and mechanism， the formula exerts a synergistic regulatory effect across multiple key pathological pathways， including the regulation of coagulation function， the maintenance of vascular structure and function， anti-inflammatory and immunomodulatory actions， the mitigation of oxidative stress， and the modulation of programmed cell death （such as pyroptosis and ferroptosis）. This systematically demonstrates its scientific rationale， which is based on integrated regulation through multiple constituents， multiple targets and multiple pathways. In terms of clinical application， the formula has expanded from cardiovascular diseases to multiple disciplines， including gastroenterology， respiratory medicine， urology， neurology， endocrinology， gynaecology and andrology， with evidence-based medical evidence continuing to accumulate. Current research still faces bottlenecks such as a relatively low level of clinical evidence， insufficient systems biology analysis of the mechanisms underlying the compound’s formulation， and a weak correlation between quality control indicators and therapeutic efficacy. Future efforts should focus on conducting multicentre randomised controlled trials for conditions where the formula demonstrates particular efficacy， deepening research into the relationship between integrated pharmacology and spectrum-efficacy relationship， and promoting the precise application and formulation innovation of classical herbal formulas.

Xuefu zhuyu decoction is a classic formula for promoting blood circulation and resolving blood stasis， characterised by its remarkable ability to treat different diseases with the same approach. Qi stagnation and blood stasis， the primary syndrome for which this formula is indicated， has been found through modern medical research to be intrinsically linked to a wide range of pathophysiological processes， including microcirculatory disorders， abnormalities in hemorheology， inflammatory responses and endothelial dysfunction； which opens up vast scope for the innovative application of traditional formulas. In terms of pharmacological effect and mechanism， the formula exerts a synergistic regulatory effect across multiple key pathological pathways， including the regulation of coagulation function， the maintenance of vascular structure and function， anti-inflammatory and immunomodulatory actions， the mitigation of oxidative stress， and the modulation of programmed cell death （such as pyroptosis and ferroptosis）. This systematically demonstrates its scientific rationale， which is based on integrated regulation through multiple constituents， multiple targets and multiple pathways. In terms of clinical application， the formula has expanded from cardiovascular diseases to multiple disciplines， including gastroenterology， respiratory medicine， urology， neurology， endocrinology， gynaecology and andrology， with evidence-based medical evidence continuing to accumulate. Current research still faces bottlenecks such as a relatively low level of clinical evidence， insufficient systems biology analysis of the mechanisms underlying the compound’s formulation， and a weak correlation between quality control indicators and therapeutic efficacy. Future efforts should focus on conducting multicentre randomised controlled trials for conditions where the formula demonstrates particular efficacy， deepening research into the relationship between integrated pharmacology and spectrum-efficacy relationship， and promoting the precise application and formulation innovation of classical herbal formulas.

ObjectiveTo elucidate the epidemiological characteristics, evolution of the pathogen spectrum, and spatial distribution patterns of other infectious diarrheal diseases (excluding cholera, typhoid fever, paratyphoid fever, and bacillary dysentery) in Yangpu District of Shanghai from 2005 to 2024, thereby providing a scientific basis for the formulation of targeted prevention and control strategies. MethodsInformation on other infectious diarrhea cases with a current address in Yangpu District of Shanghai, and onset dates from January 1, 2005 to December 31, 2024, was extracted from the Chinese Center for Disease Control and Prevention Information System. Data on cases, including gender, age, occupation, and pathogen testing results, were collected. Descriptive epidemiological methods were employed to analyze the temporal, spatial, and demographic distribution of reported incidence rates and the epidemiological characteristics of pathogens for other infectious diarrheal diseases in Yangpu District from 2005 to 2024. Spatial autocorrelation analyses of reported incidence rates for viral and bacterial diarrhea were conducted using Moran’s Index (Moran’s I）. Local spatial autocorrelation analyses were performed using local indicators of spatial association (LISA), with a first-order Queen contiguity spatial weight matrix, and significance was tested via 999 random permutations. Time-series and radar chart analyses were used to examine the temporal patterns of other infectious diarrhea cases caused by major pathogens. ResultsFrom 2005 to 2024, a total of 5 211 cases of other infectious diarrhea were reported in Yangpu District. The cases were predominantly males (2 714 cases, accounting for 52.08%) and children under 5 years of age (1 639 cases, accounting for 31.45%). The primary occupational groups were scattered children (1 433 cases, accounting for 27.50%) and retired personnel (1 403 cases, accounting for 26.92%). The annual average reported incidence rate was 20.36/100 000, showing an overall fluctuating trend with peaks around 2009 and 2024. Peak incidence occurred in summer and autumn (July‒September), with the highest reported incidence rate observed in summer (June‒August) (7.31/100 000). Children under 5 years of age (116.00/100 000) and adults aged 60 and older (21.39/100 000) were the top two age groups in terms of reported incidence. Global spatial autocorrelation analyses showed that the reported incidence rates of viral diarrhea across the sub-districts in Yangpu District in 2020 exhibited a significant positive spatial correlation (Moran’s I =0.30, P=0.016). The spatial autocorrelation of reported incidence rates of viral diarrhea in each sub-district for the periods 2008‒2019 and 2021‒2024 was not statistically significant (all P>0.05). Local spatial autocorrelation analyses of viral diarrhea incidence in 2020 revealed that Xinjiangwancheng Sub-district exhibited a low‑low clustering trend (local Moran’s I =0.49, P=0.018), while Dinghai Road Sub-district exhibited a high‑high clustering trend (local Moran’s I =1.33, P=0.024). The global spatial autocorrelation of reported incidence rates of bacterial diarrhea across the sub-districts of Yangpu District from 2005 to 2024 was not statistically significant (all P>0.05). Among the 5 211 cases, 4 049 had definitive pathogen test results. Bacterial diarrhea accounted for a relatively high proportion (55.52%, 2 248/4 049). The pathogens with the highest proportions were rotavirus (32.33%, 1 309/4 049), Vibrio spp. (31.69%, 1 283/4 049), Salmonella spp. (19.63%, 795/4 049), and norovirus (9.16%, 371/4 049). The radar chart showed that diarrhea cases caused by norovirus had no obvious seasonality, rotavirus cases were mainly concentrated in winter, and cases caused by Salmonella spp. and Vibrio spp. were mainly concentrated in summer and autumn. Among cases under 20 years of age, rotavirus accounted for a relatively high proportion, especially in children under 5 years of age. Among cases aged 20 years and older, Vibrio spp. and Salmonella spp. accounted for relatively high proportions. ConclusionFrom 2005 to 2024, other infectious diarrhea in Yangpu District of Shanghai was most prevalent in summer and autumn. Children under 5 years of age and adults aged 60 years and older were high-risk groups. In 2020, Dinghai Road Sub-district was a high-risk area for viral diarrhea. Rotavirus, Vibrio spp., Salmonella spp., and norovirus were the dominant pathogens. Prevention and control efforts for other infectious diarrhea should be strengthened among key populations (e.g., children under 5 years of age and adults aged 60 years and older) and in high-risk areas such as Dinghai Road Sub-district. During summer and autumn, priority should be given to the prevention and control of bacterial diarrhea caused by Salmonella spp. and Vibrio spp., especially among individuals aged 20 years and older (particularly those aged 60 and above). During winter, priority should be given to the prevention and control of diarrhea caused by rotavirus infection among individuals under 20 years of age, particularly children under 5 years of age.

ObjectiveTo investigate the mechanism of modified Si Junzitang and Shashen Maidong Tang ［Yiqi Yangyin Jiedu prescription （YQYYJD）］ in enhancing the sensitivity of cisplatin in epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI）-resistant lung adenocarcinoma cells based on aerobic glycolysis. MethodsThe effects of different concentrations of YQYYJD （0， 2， 3， 4， 5， 6， 7， 8 g·L^-1） and cisplatin （0， 3， 6， 9， 12， 15， 18， 21， 24， 27 mg·L^-1） on the proliferation and activity of PC9/GR cells were detected by the cell counting kit-8 （CCK-8） assay after 24 hours of intervention. The half-maximal inhibitory concentration （IC₅₀） for PC9/GR cells was calculated to determine the concentrations used in subsequent experiments. PC9/GR cells were divided into blank group （complete medium）， YQYYJD group （5 g·L^-1）， cisplatin group （12 mg·L^-1）， and combined group （YQYYJD 5 g·L^-1 + cisplatin 12 mg·L^-1）. After 24 hours of intervention， cell viability was measured using CCK-8 assay. Cell proliferation was assessed by colony formation assay， and cell migration was evaluated by scratch and Transwell assays. Glucose consumption， lactate production， and adenosine triphosphate （ATP） levels were measured by colorimetric assays. The expression levels of glycolysis-related proteins， including hexokinase 2 （HK2）， phosphofructokinase P （PFKP）， pyruvate kinase M2 （PKM2）， lactate dehydrogenase A （LDHA）， glucose transporter 1 （GLUT1）， and monocarboxylate transporter 4 （MCT4）， were determined by Western blot. ResultsBoth YQYYJD and cisplatin inhibited the viability of PC9/GR cells in a concentration-dependent manner. The IC₅₀ of PC9/GR cells for YQYYJD and cisplatin were 5.15 g·L^-1 and 12.91 mg·L^-1， respectively. In terms of cell proliferation， compared with the blank group， the cell survival rate and the number of colonies formed in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in cell survival rate and colony formation （P<0.01）. In terms of cell migration， compared with the blank group， the cell migration rate and the number of cells passing through the Transwell membrane in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group exhibited a further significant reduction in cell migration rate and the number of cells passing through the Transwell membrane （P<0.01）. In terms of glycolysis， compared with the blank group， glucose consumption， lactate production， and ATP levels in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in glucose consumption， lactate production， and ATP levels （P<0.05）. Compared with the blank group， the protein expression levels of HK2， PFKP， PKM2， and LDHA in the YQYYJD， cisplatin， and combined groups were significantly decreased （P<0.01）. The combined group showed a further significant reduction in the expression levels of these proteins compared with the YQYYJD and cisplatin groups （P<0.01）. No significant differences were observed in the protein expression levels of GLUT1 and MCT4 among the groups. ConclusionYQYYJD can synergistically inhibit the proliferation and migration of PC9/GR cells and enhance their sensitivity to cisplatin. The mechanism may be related to the downregulation of the expression of glycolysis-related rate-limiting enzymes， including HK2， PFKP， PKM2， and LDHA， thereby inhibiting glycolysis.

This paper summarized the clinical experience in treating ischemic stroke with jiao （角） medicine （triple-medicinal combinations）. Clinically， the combination of Roucongrong （Cistanche deserticola）-Shanyurou （Cornus officinalis）-Guijia （Testudinis Carapax et Plastrum） is used to nourish the kidneys and liver for disease mechanism of liver-kidney depletion， and foundation deficiency due to insufficient essence and blood； the combination of Xixiancao （Sigesbeckia orientalis）-Tianma （Gastrodia elata）-Gouteng （Uncaria rhynchophylla） is used to extinguish wind and eliminate dampness for treating numbness and swelling of limbs caused by ischemic stroke； the combination of Shichangpu （Acorus Tatarinowii）-Yuanzhi （Polygala tenuifolia）-Yujin （Curcumae Radix） is used to improve intelligence， refresh the brain， and clear the mind for treating cognitive impairment， memory loss， or speech difficulties caused by ischemic stroke； the combination of Banxia （Pinellia ternata）-Baizhu （Atractylodes macrocephala）- Tianma （Gastrodiae rhizoma） is used to dissolve phlegm and extinguish wind， unblock meridians and relieve dizziness for treating dizziness or headache caused by ischemic stroke； the combination of Danggui （Angelica sinensis radix）- Chuanxiong （Ligusticum chuanxiong）-Guijianyu （Euonymus alatus） is used to nourish and activate blood circulation， remove blood stasis and unblock meridians for treating weak limbs and activiry difficulty caused by ischemic stroke； the combination of Chaihu （Bupleurum chinense）-Zhiziz （Gardenia jasminoides）-Guanye Jinsitao （Hypericum perforatum） is used to soothe the liver and resolve constraint， cool the blood and calm the mind for treating emotional complications.