Objective To explore the non-invasive diagnostic criteria of magnetocardiography (MCG) for coronary microvascular dysfunction (CMVD), and its value in dynamically assessing drug treatment for CMVD. Methods Patients who presented with chest tightness or chest pain at Zhongshan Hospital, Fudan University from September 2024 to March 2025 were consecutively enrolled, and all of whom had non-obstructive coronary arteries on angiography. Using the coronary angiography-derived index of microcirculatory resistance (caIMR) as the gold standard, patients were divided into a normal microcirculation group (caIMR≤40 U) and a CMVD group (caIMR＞40 U). MCG testing was performed using a domestic device (MD-U041001, Mind Medical). Patients in the CMVD group received adenosine treatment and underwent repeat MCG after medication. Differences in MCG parameters between the two groups were analyzed, and a diagnostic model was established. The value of the diagnostic model was analyzed using receiver operating characteristic (ROC) curves. Results A total of 311 patients were included, with 135 in the normal microcirculation group and 176 in the CMVD group. The CMVD group had a significantly higher proportion of males (61.9% vs 47.4%, P＝0.012), and lower high-density lipoprotein cholesterol (HDL-C) levels ([1.16±0.31] mmol/L vs [1.24±0.29] mmol/L, P＝0.029) than the normal group. Eleven MCG parameters showed significant differences between the two groups (P＜0.05), among which increased values of mfm_QR_epav, mfm_RS_epmse, space_zeroRTrot, as well as decreased value of mfm_QR_v1 were independent predictors of CMVD. The diagnostic model based on these 11 MCG parameters yielded an area under the curve (AUC) of 0.688 (95%CI 0.629-0.747). The integrated diagnostic model combining clinical risk factors (male, smoking history, HDL-C) with MCG parameters had an AUC of 0.701 (95%CI 0.643-0.759). After adenosine treatment, patients in the CMVD group showed significant decreases in mfm_QR_epav (P＝0.010), mfm_RS_sad (P＝0.013), and mfm_RS_epmse (P＝0.046). Conclusions The model based on MCG parameters demonstrates good diagnostic ability for CMVD; dynamic changes in MCG parameters following adenosine intervention may serve as potential objective indicators for evaluating microcirculatory treatment efficacy.

ObjectiveTo evaluate the safety/efficacy of compound Kushen injection （CKI） by zebrafish model and explore the possible mechanism. MethodsZebrafish were exposed to different concentrations of CKI solution， and the mortality rate after 24 h was calculated. After exposure to sublethal concentration （10） and safe dose concentration （0） for 24 h， the safety of CKI was evaluated based on acridine orange staining for the liver， liver area changes， and liver histological sections. The inflammatory bowel disease （IBD） model of zebrafish was established with 2，4，6-trinitrobenzenesulfonic acid sol （TNBS）. The efficacy of CKI in the treatment of IBD was evaluated by the changes in the area of neutral red staining， the number of neutrophils， the area of alcian blue staining， and the contents of tight junction protein （Occludin）， zonula occludens-1 （ZO-1）， tumor necrosis factor（TNF）-α， and prostaglandin E₂（PGE₂） in the intestine of zebrafish. The mechanism of CKI in the treatment of IBD was predicted by network pharmacology and verified by real-time polymerase chain reaction（Real-time PCR）. ResultsIn the safety evaluation， compared with the blank group， the sublethal concentration of CKI could cause liver cell apoptosis， liver area reduction， loose and disordered arrangement of liver cell structure， obvious vacuolation， and other pathological characteristics of zebrafish， while these indicators showed no significant changes under safe dose conditions. In the effectiveness evaluation， compared with the model group， the safe dose of CKI could increase the neutral red staining area of the intestine in a dose-dependent manner and improve the intestinal phagocytosis function. It could reduce the accumulation of intestinal neutrophils， increase the alcian blue staining area， enhance intestinal goblet cell secretion， improve the contents of Occludin and ZO-1， and decrease the contents of TNF-α and PGE₂. Network pharmacology analysis identified 288 potential targets for CKI treatment of IBD. The top five targets obtained by protein-protein interaction （PPI） network analysis were epidermal growth factor receptor A（EGFRA）， protein kinase B1（Akt1）， heat shock protein 90（HSP90AA1）， homologous oncogene of avian sarcoma virus（SRC）， and protooncogene （JUN）. Kyoto encyclopedia of genes and genomes（KEGG） results showed that CKI may be related to the Wnt signaling pathway and cholinergic synaptic pathway in the treatment of IBD， and Real-time PCR results verified the above pathways. ConclusionExcessive use of CKI can induce obvious liver injury in zebrafish， while the rational use of CKI does not cause obvious toxic reactions and can achieve a therapeutic effect on IBD by regulating the Wnt pathway.

Objective To evaluate the safety and therapeutic efficacy of three-dimensional(3D)-printed personalized cervical correction pillows for treating cervical spondylotic radiculopathy.Methods A finite element model was established to simulate and analyze the biomechanical changes in cervical spine before and after using the pillow.Additionally,20 patients with chronic neck pain were included to analyze changes in visual analogue scale(VAS)scores,neck disability index(NDI),pressure pain threshold(PPT),Borden value,cervical lordosis,T1 slope,cervical slope,and thoracic inlet angle before and after using the pillow.Results Finite element analysis indicated that the maximum stress on vertebral bodies increased by 64.35％and the maximum stress on cartilage tissues by 5.09％after using the pillow.The Borden value improved by 45.75％.Clinical studies showed a significant reduction in VAS scores,NDI,and PPT after treatment(P＜0.05),while PPT,Borden value,cervical lordosis,T1 slope,and thoracic inlet angle significantly increased(P＜0.05).Conclusions The 3D-printed personalized cervical correction pillow is safe and effective in alleviating neck pain and improving cervical curvature,and it provides a new and effective non-surgical treatment option for cervical spondylotic radiculopathy,with significant clinical implications.

Objective To explore the lung protective effect of pressure controlled ventilation-volume guaranteed(PCV-VG)combined with driving pressure(DP)guided lung protective ventilation strategy in patients undergoing thoracoscopic and laparoscopic radical esophagectomy.Methods 70 patients scheduled for elective thoracoscopic and laparoscopic radical esophagectomy were allocated into two groups using a random number table method:Conventional lung protective ventilation strategy group(group C)and DP guided lung protective ventilation strategy under PCV-VG mode group(group P),35 case in each group.Peak airway pressure(Ppeak),plateau pressure(Pplat),dynamic compliance(Cdyn)and DP were compared between the two groups at 5 minutes after intubation(T1),30 min after pneumoperitoneum established(T2),just prior to one lung ventilation(OLV)(T3),30 min after OLV(T4),60 min after OLV(T5)and 15 min from recovery of two lung ventilation(TLV)(T6).The blood pressure(BP),heart rate(HR),arterial partial pressure of oxygen(PaO2),partial pressure of carbon dioxide in arterial blood(PaCO2)and pH were recorded before anesthesia(T0),T2,T3,T4,T5 and T6 time points.The occurrence of postoperative pulmonary complications(PPCs)also recorded.Results Compared with group C,Ppeak in group P at T1,T2,T4,T5 and T6 time points was significantly decreased,and Cdyn was obviously increased,the differences were statistically significant(P＜0.05).At the T1,T4,T5 and T6 time points,the DP was lower in group P compared to group C,and Pplat at T6 time point was lower than that in group C,the differences were statistically significant(P＜0.05).At the time points of T4 and T5,the PaO2 in group P was higher than that in Group C,and the PaCO2 at T6 time point was also higher than that in group C,the differences were statistically significant(P＜0.05).The comparison of PaCO2 at T0,T2,T3,T4 and T5 time points of the two groups,the difference was not statistically significant(P＞0.05).Comparison of pH between the two groups,the difference was not statistically significant at all time points(P＞0.05).The systolic blood pressure(SBP)of group P was higher than that of group C at the T4 time point,and the diastolic blood pressure(DBP)was lower than that of group C at T6 time point,and the differences were statistically significant(P＜0.05);There were no significant differences in SBP and DBP at T0,T2,T3 and T5 time points,and HR at each time point between the two groups(P＞0.05).There was no statistically significant difference in the occurrence of PPCs within 7 d after operation between the two groups(P＞0.05).Conclusion DP guided lung protective ventilation strategy under PCV-VG mode can improve intraoperative respiratory mechanics,and increase oxygenation during OLV in patients undergoing thoracoscopic and laparoscopic radical esophagectomy,but it does not significantly affect the incidence of PPCs within 7 d after operation.It is worthy clinical significant.

Objective To construct an operational indicator system for infectious disease monitoring and early warning,and provide data support and decision-making basis for monitoring and early warning.Methods A preli-minary indicator framework was constructed through literature analysis and expert interviews,and expert consultation was conducted using the Delphi method.A total of 30 experts were selected.The score of the importance of indica-tors based on the consultation results was calculated,and the weight was determined.Results The response rates of expert consultation questionnaires from two rounds were both 100％,with expert authority coefficients(reliabili-ty coefficient)being 0.87 and 0.88 for the first and second rounds,respectively.Kendall's W coefficients ranged from 0.137 to 0.424,with statistically significant differences(all P＜0.001).Coefficients of variation for all indi-cators were＜0.25,indicating that expert opinions tend to be consistent and the results were authoritative and relia-ble.The finally constructed indicator system encompassed 4 first-level,25 second-level,and 68 third-level indica-tors.Conclusion The operational indicator system for infectious disease monitoring and early warning developed in this study can provide a basis for the practice of infectious disease monitoring and early warning as well as related scientific decision-making.

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic

Rodent models play a crucial role in research on human periodontal diseases,providing key evidence for investigation into the pathological mechanisms of periodontal bone defects.Relevant research in the field involves gene expression,inflammatory regulation mechanisms,host-microbial interactions,as well as disease resolution and healing processes.Research methodology in the field falls under 2 categories-periodontal inflammation models and surgical defect models.The former simulates periodontal defects by inducing periodontal diseases,while the latter constructs clinically simulated periodontal defects through surgical removal of periodontal tissue.However,the currently available animal models of periodontitis face challenges in simultaneously capturing the disease complexity,tracking dynamic repair processes,and meeting translational needs.Herein,we reviewed and summarized the methods and characteristics of periodontal disease modeling in recent years.We proposed the establishment of a multimodal assessment framework integrating technologies such as spatial transcriptomics,single-cell sequencing,and in vivo fluorescence imaging,which may serve as a critical pathway for overcoming existing research challenges.

Objective:To explore the efficacy and safety of B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor and epidermal growth factor receptor (EGFR) inhibitor combined with immune checkpoint inhibitor in microsatellite stable (MSS) BRAF V600E metastatic colorectal cancer (mCRC) patients.Methods:The data and outcomes of mCRC patients with MSS BRAF V600E who received BRAF inhibitor, EGFR inhibitor combined with immune checkpoint inhibitor in Tianjin Medical University Cancer Hospital from May 2022 to April 2024 were retrospectively collected.Results:A total of 12 mCRC patients were included in this study, the objective response rate was 50.0%, the disease control rate was 66.7%, and the median disease control time of patients who achieved objective response was 8.0 months. The median progression-free survival was 6.8 months and the median overall survival was 8.4 months. Overall adverse reactions were controllable, the most common treatment-related adverse events were fatigue (8 cases), fever (5 cases), and rash (4 cases). There were no grade 4 adverse event, serious adverse event, and treatment-related death.Conclusion:BRAF inhibitor and EGFR inhibitor combined with immune checkpoint inhibitor show good efficacy and controllable safety in BRAF V600E mCRC patients.