This paper aimed to investigate the therapeutic effect and mechanism of action of the Yiqi Fumai Formula(YQFM), a kind of traditional Chinese medicine(TCM), on mice with experimental heart failure based on the "heart-gut axis" theory. Based on the network pharmacology integrated with the group collaboration algorithm, the active ingredients were screened, a "component-target-disease" network was constructed, and the potential pathways regulated by the formula were predicted and analyzed. Next, the model of experimental heart failure was established by intraperitoneal injection of adriamycin at a single high dose(15 mg·kg~(-1)) in BALB/c mice. After intraperitoneal injection of YQFM(lyophilized) at 7.90, 15.80, and 31.55 mg·d~(-1) for 7 d, the protective effects of the formula on cardiac function were evaluated using indicators such as ultrasonic electrocardiography and myocardial injury markers. Combined with inflammatory factors in the cardiac and colorectal tissue, as well as targeted assays, the relevant indicators of potential pathways were verified. Meanwhile, 16S rDNA sequencing was performed on mouse fecal samples using the Illumina platform to detect changes in gut flora and analyze differential metabolic pathways. The results show that the administration of injectable YQFM(lyophilized) for 7 d significantly increased the left ventricular end-systolic internal diameter, fractional shortening, and ejection fraction of cardiac tissue of mice with experimental heart failure(P<0.05). Moreover, markers of myocardial injury were significantly decreased(P<0.05), indicating improved cardiac function, along with significantly suppressed inflammatory responses in cardiac and intestinal tissue(P<0.05). Additionally, the species of causative organisms was decreased, and the homeostasis of gut flora was improved, involving a modulatory effect on PI3K-Akt signaling pathway-related inflammation in cardiac and colorectal tissue. In conclusion, YQFM can affect the "heart-gut axis" immunity through the homeostasis of the gut flora, thereby exerting a therapeutic effect on heart failure. This finding provides a reference for the combination of TCM and western medicine to prevent and treat heart failure based on the "heart-gut axis" theory.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Heart Failure/microbiology* ; Mice ; Mice, Inbred BALB C ; Male ; Disease Models, Animal ; Gastrointestinal Microbiome/drug effects* ; Heart/physiopathology* ; Humans ; Signal Transduction/drug effects*

This study aims to explore the intervention effects of isorhamnetin(Isor) on acute lung injury(ALI) and its regulatory effects on pyroptosis mediated by the NOD-like receptor family pyrin domain containing 3(NLRP3)/apoptosis-associated speck-like protein containing a CARD(ASC)/cysteine aspartate-specific protease-1(caspase-1) axis. In the in vivo experiments, 60 BALB/c mice were divided into five groups. Except for the control group, the other groups were administered Isor by gavage 1 hour before intratracheal instillation of LPS to induce ALI, and tissues were collected after 12 hours. In the in vitro experiments, RAW264.7 cells were divided into five groups. Except for the control group, the other groups were pretreated with Isor for 2 hours before LPS stimulation and subsequent assessments. Hematoxylin-eosin(HE) staining was used to observe pathological changes in lung tissue, while lung swelling, protein levels in bronchoalveolar lavage fluid(BALF), and myeloperoxidase(MPO) levels in lung tissue were measured. Cell proliferation toxicity and viability were assessed using the cell counting kit-8(CCK-8) method. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of interleukin-1β(IL-1β), IL-6, IL-18, and tumor necrosis factor-α(TNF-α). Protein levels of NLRP3, ASC, cleaved caspase-1, and the N-terminal fragment of gasdermin D(GSDMD-N) were evaluated using immunohistochemistry, immunofluorescence, and Western blot. The results showed that in the in vivo experiments, Isor significantly improved pathological damage in lung tissue, reduced lung swelling, protein levels in BALF, MPO levels in lung tissue, and levels of inflammatory cytokines such as IL-1β, IL-6, IL-18, and TNF-α, and inhibited the high expression of the NLRP3/ASC/caspase-1 axis and the pyroptosis core gene GSDMD-N. In the in vitro experiments, the safe dose of Isor was determined through cell proliferation toxicity assays. Isor reduced cell death and inhibited the expression levels of the NLRP3/ASC/caspase-1 axis, GSDMD-N, and inflammatory cytokines. In conclusion, Isor may alleviate ALI by modulating pyroptosis mediated by the NLRP3/ASC/caspase-1 axis.
Animals ; Pyroptosis/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Acute Lung Injury/physiopathology* ; Mice ; Mice, Inbred BALB C ; Quercetin/pharmacology* ; Caspase 1/genetics* ; CARD Signaling Adaptor Proteins/genetics* ; Male ; RAW 264.7 Cells ; Humans ; Lung/metabolism*

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

OBJECTIVE: To preliminarily investigate the effects and mechanism of action of Yishen Yangsui Formula (, YSYSF)on the recovery of neurological function in rats with degenerative cervical myelopathy. METHODS: Fifty adult SD female rats were randomly divided into control group, sham group, model group, YSYSF group and positive drug group by using randomized numerical table method. In the model group, YSYSF group and positive drug group, polyvinyl alcohol acrylamide interpenetrating network hydrogel(water-absorbent swelling material) was used to construct a rat spinal cord chronic compression model. The sham group was implanted with the water-absorbent swelling material and then removed without causing spinal cord compression. The control group, the sham group and the model group were given equal amounts of saline by gavage, the group of YSYSF was given Chinese herbal medicine soup by gavage 9.1 g·kg^-1 once a day, and the positive drug group was given tetrahexylsalicylglucoside sodium monosialate ganglioside by intraperitoneal injection 4.2 mg·kg^-1 once a day. The motor function of the rats was assessed by the BBB method after 1, 3, 7, and 14 d of drug administration. The spinal cord tissues were taken from rats executed 14 d after drug administration, and the morphological changes of the spinal cord compression site were observed by HE staining, and the expression levels of Caspase-1, GSDMD, NLRP3, PYCARD, IL-1β, and IL-18 were detected in the area of spinal cord injury by Western blot method. RESULTS: The BBB scores of the control group and the sham group were normal at all time points after modeling, which were higher than the BBB scores of the model group, the YSYSF, and the positive drug group (P<0.05). From the 3rd day after gavage, at all time points, the BBB scores of rats in the YSYSF group and the positive drug group were higher than those of rats in the model group (P<0.05). The staining pattern of HE spinal cord tissue was normal in the control group and the sham group, and the HE spinal cord in the model group was severely damaged with a large number of neuron deaths, whereas the damage to the spinal cord and neuron cells was reduced in the YSYSF group and the positive drug group. The expression levels of caspase-1, GSDMD, NLRP3, PYCARD, IL-1β and IL-18 in the spinal cord of the model group were significantly higher than those of the sham group (P<0.0001), and the expression levels of caspase-1, GSDMD, NLRP3, PYCARD, IL-1β, and IL-18 in the YSYSF group and the drug group were significantly lower than those in the model group (P<0.05). CONCLUSION YSYSF can improve the motor function of rats with degenerative cervical spinal cord disease, alleviate the pathological changes, and promote the recovery of spinal cord neurological function. The specific mechanism may be related to the inhibition of the activation of inflammatory vesicles NLRP3 and PYCARD, the reduction of the release of inflammatory factors IL-1β and IL-18, the reduction of the expression of caspase-1 and GSDMD, the reduction of cellular death, and the inhibition of inflammatory response.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Rats, Sprague-Dawley ; Pyroptosis/drug effects* ; Spinal Cord/pathology* ; NLR Family, Pyrin Domain-Containing 3 Protein ; Spinal Cord Diseases/drug therapy* ; Interleukin-1beta/metabolism*

Objective To study the damage effect of high-voltage electric shock on skin based on metabolomics,analyze its metabolic differences,and explore its injury mechanism.Methods A total of 16 SPF C57BL/6J male mice were divided into the electric shock group(head skin received electric shock treatment)and control group(head skin received electric shock acoustic-optical stimulation),and the skin appearance after treatment of mice in the two groups was observed.The histopathological changes caused by electric shock were analyzed by HE staining,EVG staining and Masson staining.GC-MS and LC-MS metabonomics were used to analyze the changes of skin metabolism spectrum and tissue metabolites after electric shock exposure,and the differential metabolites were analyzed.The obtained differential metabolites were combined and KEGG enrichment analysis was conducted.Results After high-voltage electric shock,the skin of mice could be damaged to the dermis,and the epidermis was partially thickened,lifted and separated.The structure of skin appendages in the dermis was destroyed,with a large number of inflammatory cells infiltrating and obvious swelling,accompanied by congestion,which led to severe skin inflammatory reaction and impaired skin barrier function.Metabonomics analysis suggested that the metabolites changed after electric shock exposure.KEGG enrichment analysis showed that electric shock significantly affected the central carbon metabolism pathway of cancer,pentose phosphate pathway,purine metabolism,glycine,serine and threonine metabolism processes,amino acid tRNA biosynthesis mechanism,glycerophospholipid metabolism pathway,pyrimidine metabolism pattern,glycolysis/gluconeogenesis,alanine metabolism process,glucagon signal pathway and so on.Conclusion High voltage electric shock can cause deep skin damage,disturb its energy metabolism and amino acid metabolism,and seriously interfere with its antioxidant and DNA repair system functions.

The theory of"spleen and stomach deficiency and excess transformation"originates from Huangdi Neijing,which is based on the five elements theory.It systematically elucidates the physiological interconnections and pathological transmission relationships among spleen,stomach,and the five zang and six fu viscera.This theory was continuously developed and refined by later physicians.It was first systematically summarized and deepened by LI Dongyuan in his work Piwei Lun,which elaborates on the pathological transmission relationships of other zang-fu viscera after spleen and stomach deficiency.From the perspective of LI Dongyuan's theory of"spleen and stomach deficiency and excess transformation",this paper discusses the pathological relationships between spleen-earth,lung-metal,and kidney-water,and proposes that spleen-earth deficiency is the pathological basis for the onset of allergic rhinitis.Based on the pathological evolution following spleen-earth deficiency,the traditional Chinese medicine syndromes of allergic rhinitis were categorized into three types:earth deficiency with metal weakness,earth dryness with metal desiccation,and water cold with metal excess and earth decline.The treatment of allergic rhinitis should prioritize the spleen-earth,employing acrid and dispersing herbs with light properties to elevate the spleen,sweet-warm and sour-astringent herbs to tonify the spleen,and diuretic and dampness-resolving herbs to activate the spleen,thereby restoring spleen-earth function.Simultaneously,treatment should regulate lung-metal and kidney-water according to different pathological evolutions,incorporating cold-cool or acrid-warm herbs as appropriate,combining cold and warm properties,and treating both the manifestation and root cause of the disease.

AIM To investigate the promotional effects of esculin combined with bone marrow mesenchymal stem cells(BM-MSCs)transplantation on the repair of spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the esculin group for gavage of 20 mg/kg esculin,the BM-MSCs group for tail vein injection of 1 mL of 1×106/mL BM-MSCs,and the combinaiton treatment group.The SCI rat model was established using Allen's method,followed by the 14 days consecutive corresponding drug administration starting from the 2nd day after modeling.On days 3,7 and 14 of drug administration,the rats had their hind limbs motor function evaluated by the BBB scoring;and their footprint experiment conducted on the 14th day after modeling.After 14 days of administration,the rats had their morphological changes of spinal cord tissue observed with HE staining and Nissl staining;their activities of SOD and GSH,and level of MDA in spinal cord tissue detected by kits;their expressions of MAP2,GAP43 and GFAP in spinal cord tissue detected by immunofluorescence;and their expressions of NQO-1,Nrf-2,Bcl-2 and Bax proteins in spinal cord tissue detected by Western blot.RESULTS Compared with the model group,the groups interved with esculin,or BM-MSCs,or the combination treatment showed improvements in hind limb function and spinal cord tissue morphology(P＜0.05);decreased MDA levels(P＜0.05);increased SOD and GSH activities(P＜0.05);increased MAP2 and GAP43 fluorescence intensity(P＜0.05);decreased GFAP fluorescence intensity(P＜0.05);increased NQO-1,Nrf-2 and Bcl-2 protein expressions(P＜0.05);and decreased Bax protein expression(P＜0.05).And the combination treatment group was observed with an even better effects(P＜0.05).CONCLUSION The combination of esculin and BM-MSCs transplantation can effectively improve the spinal cord tissue damage and hind limb function in SCI rats.This effect may be achieved by activating the Nrf-2/NQO-1 signaling pathway to inhibit oxidative stress response,thereby reducing neuronal apoptosis,blocking glial scar formation,and promoting stem cell differentiation to rebuild neurons.

Objective:To assess the viability of reducing radiation dose, contrast media volume, injection flow rate and contrast medium concentration (quadruple low-dose protocol) by utilizing virtual monoenergetic images (VMI) in photon-counting detector CT (PCD-CT) for aortic CT angiography (CTA), while maintaining image quality in comparison to images obtained from energy-integrating detector CT (EID-CT).Methods:From April 2024 to June 2024, a total of 40 participants who underwent aortic CTA on PCD-CT were prospectively enrolled in the experimental group (PCD-CT group), while 40 patients with similar baseline characteristics who had previously undergone aortic CTA using EID-CT were retrospectively selected for the conventional group (EID-CT group). The EID-CT group used a tube voltage of 90 kVp, a contrast media volume of 60 ml of contrast, an injection flow rate of 3 ml/s, and a contrast concentration of 350 mgI/ml; the PCD-CT group used the QuantumPlus mode, with a tube voltage of 140 kVp, a total amount of iodine in the contrast media of 140 mgI/kg, and an injection flow rate=contrast media volume/(delay time+scan time), and a contrast media concentration of 320 mgI/ml. VMIs in PCD-CT group were reconstructed in 5-keV intervals ranging from 45 to 65 keV. The effective radiation dose and contrast injection protocols were recorded and compared between two groups. Objective image quality assessment was performed for each group. CT attenuation, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured at five anatomical locations (ascending aorta, aortic arch, descending aorta, abdominal aorta, and right common iliac artery), and image noise was recorded. Subjective image quality was independently evaluated by two readers using a 5-point Likert scale in a blinded manner. Based on data normality, the one-way ANOVA or Kruskal-Wallis test was used for image quality assessment, with Bonferroni-corrected post-hoc analysis for multiple comparisons.Results:There were no significant differences in the baseline characteristics between two groups (all P0.05). The PCD-CT group demonstrated significantly lower effective radiation dose [(3.88±0.65) mSv vs. (5.97±1.15)mSv], contrast media volume [(29.25±4.56) ml vs. 60 ml], and injection rate [(2.65±0.42) ml/s vs. 3 ml/s] than the EID-CT group, with reductions of 35%, 51%, and 12%, respectively (all P0.001). For objective image quality, except for the ascending aortic CT attenuation, the CT attenuation, SNR, and CNR of other vessels in the 55 keV PCD-CT group were comparable to those in the EID-CT group. Additionally, the difference in image noise between these two groups was not statistically significant ( P0.05). Concerning subjective image quality, at 55 keV, the PCD-CT group had similar image noise scores and vessel attenuation scores (both P0.05) and better visualization of renal artery branching ( P=0.001) compared to the EID-CT group. Conclusion:In comparison to EID-CT, the use of a 55 keV image in PCD-CT for aortic CTA has demonstrated reductions in radiation dose, contrast media volume, injection flow rate and contrast medium concentration, while maintaining image quality.

Objective:To evaluate the feasibility of head and neck vascular imaging using photon-counting detector computed tomography (PCD-CT) combined with a “quadruple lows” protocol—characterized by low contrast media volume, low iodine concentration, low injection rate, and low radiation dose—and to compare the image quality with that obtained by energy-integrating detector CT (EID-CT).Methods:A total of 105 patients with suspected cerebrovascular disease were prospectively enrolled at the First Affiliated Hospital of Zhengzhou University between April and June 2024. Patients were randomly assigned to three groups ( n=35). Group A underwent conventional head and neck CTA using EID-CT. Group B underwent PCD-CT with a protocol involving ultra-low contrast media volume, low iodine concentration, and low injection rate. Group C underwent PCD-CT with the full “quadruple low” protocol. Objective image quality parameters—including CT attenuation, image noise (standard deviation, SD), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR)—were measured at the ascending aorta, common carotid artery, internal carotid artery, vertebral artery, basilar artery, posterior cerebral artery, and middle cerebral artery. Two radiologists independently rated subjective image quality using a 5-point Likert scale. Differences among groups were analyzed using one-way ANOVA and the Kruskal-Wallis test. Results:Compared to Group A [contrast volume: (42.78±6.64)ml], contrast agent volume was significantly reduced in Groups B and C[ (26.26±4.45) ml and (26.54±3.83)ml, respectively], demonstrating reductions of 39% and 38% (both P<0.01). The iodine concentration was 320 mg/ml in Groups B and C, lower than 350 mg/ml in Group A (8.5%). The injection rate was also reduced in Groups B and C [(3.39±0.61) and (3.55±0.51)ml/s, respectively] compared to Group A [(4.28±0.66) ml/s], with reductions of 21% and 17% (both P<0.01). The effective dose (ED) was similar between Groups A and B [(1.40±0.15) vs. (1.40±0.19)mSv, P>0.05], while Group C demonstrated a significantly lower ED [(0.99±0.09) mSv], with a reduction of 30% compared to Group A and 29% compared to Group B (both P<0.01).In terms of objective image quality, significant differences in image noise (SD) were observed among the three groups at the vertebral artery, internal carotid artery, posterior cerebral artery, and middle cerebral artery (all P<0.05). Groups B and C showed significantly lower SD compared to Group A ( P<0.05), with no significant difference between B and C ( P>0.05). SNR was significantly higher in Groups B and C than in Group A at multiple vascular segments (all P<0.05). CNR differed only at the internal carotid artery, where Groups B and C demonstrated superior performance compared to Group A ( P<0.05).Subjective image quality scores showed no significant difference between Groups A and C ( P>0.05), while Group B had significantly higher scores than both A and C ( P<0.05). All images were deemed diagnostically acceptable. Conclusion:Compared with conventional EID-CT, PCD-CT combined with a “quadruple lows” protocol enables substantial reductions in contrast media and radiation dose while further improving image quality in head and neck CTA.

Objective:To evaluate the safety of neoadjuvant therapy with pembrolizumab combined with 5-fluorouracil (5-FU) and cisplatin in patients with advanced temporal bone squamous cell carcinoma (TBSCC), and its impact on tumor response rate and disease-free survival (DFS).Methods:This prospective, single-arm, open-label clinical study enrolled patients with advanced (Stage Ⅲ/Ⅳ) TBSCC from Sun Yat-sen Memorial Hospital. Patients received 2-3 cycles of neoadjuvant therapy with pembrolizumab, 5-FU, and cisplatin, followed by definitive surgery. Postoperatively, patients received 6 cycles of pembrolizumab combined with radiotherapy. The primary endpoint was the 2-year disease-free survival (DFS) rate. Secondary endpoints included objective response rate (ORR) and safety indicators. Survival analysis was performed using the Kaplan-Meier method. Adverse events (AE) were assessed using the National Cancer Institute′s Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Statistical analyses were conducted using SPSS software, version 22.0.Results:From August 2021 to April 2024, 16 patients with advanced TBSCC were enrolled (13 males and 3 females), with a median age of 54 years and a median follow-up time of 2.32 years. Following neoadjuvant therapy, the objective response rate (ORR) was 64.3% (9/14), and the disease control rate (DCR) was 92.9% (13/14). The 2-year DFS rate was 86.6%. Common treatment-related adverse events (TRAE) included leukopenia (56.3%, 9/16), nausea and vomiting (50.0%, 8/16), diarrhea, oral mucositis, and elevated liver function tests (25.0%, 4/16). One patient (6.25%) experienced a grade 3 adverse event.Conclusion:Neoadjuvant pembrolizumab-chemotherapy significantly enhances objective response rate and disease-free survival in advanced TBSCC.