OBJECTIVE To investigate the mechanism by which the traditional Chinese medicine formula Xibining Ⅱ modulates cold-stimulus pain sensitivity in rats with cold-damp obstruction-type knee osteoarthritis （KOA） based on the SET domain bifurcated histone lysine methyltransferase 2 （SETDB2）/histone H3 lysine 9 trimethylation （H3K9me3） signaling axis. METHODS Fifty SD rats were randomly divided into control group （intragastric administration and intrathecal injection of equal volumes of normal saline）， model group （intragastric administration and intrathecal injection of equal volumes of normal saline）， Xibining Ⅱ low- and high-dose groups （4， 8 g/kg Xibining Ⅱ， intragastric administration）， and high-dose of Xibining Ⅱ+small interfering RNA （siRNA） group （8 g/kg of Xibining Ⅱ via intragastric administration and intrathecal injection of SETDB2 siRNA at 0.2 mmol/L， 20 μL per rat）， with 10 rats in each group. Except for the control group， cold-damp obstruction-type KOA model was induced in other groups. Drug administration commenced 14 days post-modeling and continued for 28 days. Following the final administration， the following were assessed： behavioral changes in cold-stimulation pain sensitivity， histopathological changes in the articular cartilage of the knee joint， the contents of inflammatory factors [tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）] and pain mediators [calcitonin gene-related peptide （CGRP）， nerve growth factor （NGF）]， as well as the expressions of SETDB2/H3K9me3 signaling axis，inflammatory factors and pain mediators related proteins and mRNAs in dorsal root ganglion （DRG） tissue. RESULTS After 28 days of drug administration， compared with the model group， Xibining Ⅱ low- and high-dose groups exhibited significantly prolonged cold-stimulus paw withdrawal latency （P＜0.05）； the number of positive responses in the acetone low-temperature test was significantly reduced （P＜0.05）； Mankin score and the Osteoarthritis Research Society International score for knee joint tissue， as well as the levels of inflammatory factors and pain mediators in the serum and their expression in DRG tissue were all significantly decreased （P＜0.05）； the protein expressions of SETDB2 and H3K9me3 in DRG tissue were significantly increased （P＜0.05）. Intrathecal injection of SETDB2 siRNA reversed the above effects of high-dose of Xibining Ⅱ （P＜0.05）. CONCLUSIONS Xibining Ⅱ may alleviate inflammatory and pain responses by activating the SETDB2/H3K9me3 signaling axis， ultimately improving cold-stimulus pain sensitivity in rats with cold-damp obstruction-type KOA.

Chronic heart failure （CHF） is a major global public health problem， and myocardial infarction is one of its main causes. The mouse model of heart failure induced by coronary artery ligation is widely used in the study of CHF， while the TCM syndrome attributes of this model have not yet been clarified. According to the theory of correspondence between prescriptions and syndromes， the method of syndrome identification by prescription efficacy is an important means of current syndrome research of animal models. This method deduces the syndrome characteristics of animal models through prescription efficacy. Taking the four basic syndrome elements of Qi， blood， Yin and Yang as the classification reference， this study used coronary artery ligation to construct a mouse model of CHF and treated the model with four representative TCM injections with the effects of replenishing Qi， warming Yang， nourishing Yin， and activating blood and enalapril. Echocardiography， tongue color parameters， histopathology， serum N-terminal pro-brain natriuretic peptide （NT-proBNP） and cardiac troponin Ⅰ （cTnⅠ） levels， and systematically explored the TCM syndrome attributes of this model. The results showed that the coronary ligation model presented an obvious cardiac function decline， myocardial fibrosis， infarct size expansion， and purple dark tongue， which were consistent with the basic syndrome characteristics of blood stasis in CHF. Danhong injection had significant effects of improving the cardiac function， alleviating myocardial fibrosis， and reducing serum NT-proBNP and cTnⅠ levels. Huangqi Injection and Shenfu injection can improve the cardiac function and tongue color parameters， with limited effects. The effect of Shenmai injection group was not obvious. This study verifies that the established model conforms to blood stasis syndrome through the method of syndrome identification by prescription efficacy， which provides an experimental basis for the study of TCM syndrome mechanism of CHF.

Objective: To explore the association between takeout fast foods and sugar sweetened beverage consumption with co-occurrence of anxiety and depressive symptoms among first year junior high school students in Yunnan Province, so as to provide theoretical basis for the prevention of anxiety and depressive symptoms co-occurrence among adolescents. Methods: A random cluster sampling involving 8 500 first year junior high school students in 11 counties in Yunnan Province was conducted by a questionnaire survey from October to December 2022. The Depression Anxiety Stress Scale-21 (DASS-21) was applied to assess anxiety and depressive symptoms in first year junior high school students. Chi-square test was used to compare the anxiety-depression co-occurrence symptoms of first year junior high school students with different demographic characteristics. The association between takeout fast foods and sugar sweetened beverage consumption with co-occurrence of anxiety and depressive symptoms of adolescents was analyzed by binary Logistic regression models. Results: The detection rate of co-occurrence of anxiety and depression symptoms among first year junior high school students in Yunnan Province was 26.92%. After controlling for demographic variables and other confounders, takeout fast foods and sugar sweetened beverage consumption( OR=1.50, 95%CI =1.27-1.77) was associated with anxiety-depression co-occurrence symptoms among first year junior high school students in Yunnan Province ( P <0.01). Stratified analysis showed that both Han ( OR=1.37, 95%CI =1.07-1.77) and ethnic minorities ( OR=1.60, 95%CI =1.29-2.00) exhibited statistically significant associations between takeout fast foods and sugar sweetened beverage consumption with co-occurrence of anxiety and depressive symptoms(both P <0.05). Conclusions Takeout fast foods and sugar sweetened beverage consumption increases the risk of co-occurrence of anxiety and depressive symptoms among first year junior high school students in Yunnan Province. It is recommended to strengthen guidance on the consumption of such products among junior high school students to prevent co-occurrence of anxiety and depressive symptoms.

Objective The aim of this study was to investigate whether downregulation of FK506 binding protein 4(FKBP4)could inhibit the malignant progression of non-small cell lung cancer(NSCLC)by blocking the PI3K/Akt/mTOR signaling pathway.Methods NSCLC A549,H1975,H358 and PC-9 cell lines,as well as human bronchial epithelial cells(HBE)were routinely cul-tured.The expression of FKBP4 in these cells was detected by qRT-PCR,and NSCLC cell lines with the most significant different ex-pression of FKBP4 compared with HBE cells was screened.FKBP4 siRNA and NC siRNA were transfected into A549 cells,which were divided into the si-FKBP4 group and NC group.CCK-8 assay was used to detect the proliferative ability of si-FKBP4 group and NC group,flow cytometry was used to detect the apoptosis rate,scratch healing assay was used to detect the migration ability,Transwell assay was used to detect the invasion ability,and Western blot was used to detect the total and phosphorylation protein expression of PI3K and its downstream effectors Akt and mTOR.Results The expression of FKBP4 in A549 cells,H1975 cells,H358 cells and PC-9 cells were significantly higher than those in HBE cells(P<0.05),and its expression in A549 cells was the highest(P<0.001).Downregulation of FKBP4 could inhibit the proliferation,invasion and migration of A549 cells and promote the apoptosis of A549 cells(P<0.001).In addition,downregulation of FKBP4 also could inhibit the phosphorylation of PI3K,Akt and mTOR,resulting in bloc-king the PI3K/Akt/mTOR signaling pathway.Conclusion Downregulation of FKBP4 can inhibit the proliferation,invasion and mi-gration of NSCLC cells by blocking the PI3K/Akt/mTOR signaling pathway,and promote the apoptosis of NSCLC cells.

Objective To explore the diagnostic value of serum C-reactive protein(CRP),serum amyloid A(SAA)and procalcitonin(PCT)combined with lactate dehydrogenase(LDH)and adenosine deaminase(ADA)in cerebrospinal fluid for elderly patients with central nervous system infection and their differential significance for different infection types.Methods A total of 97 elderly patients with central nervous system infection were enrolled as the infection group,including 31 cases with tuberculous meningitis(tuberculous meningitis group),36 cases with suppurative meningitis(suppurative meningitis group)and 30 cases with viral meningitis(viral meningitis group).A total of 97 patients with normal laboratory examination indexes who were treated due to primary headache during the same period were enrolled as the control group.The samples of fasting elbow venous blood were collected in the early morning of the next day after admission,and the serum was isolated to detect CRP and SAA levels.When consultation,lumbar puncture was performed to collect cerebrospinal fluid for the detection of LDH and ADA levels.The differences in above indexes were compared between groups,and diagnostic efficiency of each index and combined detection for central nervous system infection in elderly was analyzed by receiver operating characteristic(ROC)curves.Results The serum levels of CRP,SAA and PCT,and LDH and ADA in cerebrospinal fluid were higher in the infection group than those in the control group(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)values of serum CRP,SAA and PCT,and cerebrospinal fluid LDH and ADA,and combined detection in the diagnosis of central nervous system infection were all>0.70(P＜0.05),showing good predictive efficiency and diagnostic efficiency,and the diagnostic efficacy of combined detection was the best.The cut-off values of serum CRP,SAA and PCT,cerebrospinal fluid LDH and ADA were 6.32 mg/L,33.86 mg/L,2.81 μg/L,33.53 U/L and 1.99 U/L,respectively.The serum levels of CRP,SAA and PCT were the highest in the suppurative meningitis group,while which were the lowest in the viral meningitis group.The cerebrospinal fluid levels of LDH and ADA were the highest in the tuberculous meningitis group,while which were the lowest in the viral meningitis group(P＜0.05).Conclusion The combined detection of serum CRP,SAA and cerebrospinal fluid PCT and LDH has certain diagnostic value for elderly central nervous system infection,which is beneficial to identify infection types.

Bacterial infection is a major threat to global public health,and can cause serious diseases such as bacterial skin infection and foodborne diseases.It is essential to develop a new method to rapidly di-agnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time.In this work,we developed a 4-mercaptophenylboronic acid gold nanoparticles(4-MPBA-AuNPs)-functionalized hydrogel microneedle(MPBA-H-MN)for bacteria detection in skin inter-stitial fluid.MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min.Surface enhanced Raman spectroscopy(SERS)detection was then performed and combined with ma-chine learning technology to distinguish and identify a variety of bacteria.Overall,the capture efficiency of this method exceeded 50％.In the concentration range of 1 × 10 7 to 1 × 10 10 colony-forming units/mL(CFU/mL),the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration.Using random forest(RF)-based machine learning,bacteria were effectively distinguished with an accuracy of 97.87％.In addition,the harmless disposal of used MNs by photothermal ablation was convenient,environmentally friendly,and inexpensive.This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.

Advancements in artificial intelligence(AI)and emerging technologies are rapidly expanding the exploration of chemical space,facilitating innovative drug discovery.However,the transformation of novel compounds into safe and effective drugs remains a lengthy,high-risk,and costly process.Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development.Despite this need,no comprehensive tool currently supports systematic evaluation and efficient screening.Here,we present druglikeFilter,a deep learning-based framework designed to assess drug-likeness across four critical dimensions:1)physicochemical rule evaluated by systematic determination,2)toxicity alert investigated from multiple perspectives,3)binding affinity measured by dual-path analysis,and 4)compound synthesizability assessed by retro-route prediction.By enabling automated,multidimensional filtering of compound libraries,druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates,which can be freely accessed at https://idrblab.org/drugfilter/.

Objective To identify the basic and clinical questions of the Guidelines for Preventive Treatment of Diseases in Endometriosis based on the Delphi method.Methods Based on the preliminary literature review,preliminary pan-research and expert interviews,the questions of the Guidelines for Preventive Treatment of Diseasesin in Endometriosis were drafted.Totally 15 experts were selected for two rounds of Delphi method expert correspondence and the results were statistically analyzed to finalize the questions for inclusion in the guidelines.Results A total of 65 entries were finally identified for inclusion in the guideline questions and condensed into 8 guideline questions.The quality control of the two rounds of Delphi method was good.The positive coefficient of experts in both rounds was 100%.The coefficient of authority of experts was>0.70.In the degree of Delphi coordination,the mean coefficients of variation were 0.23 and 0.26,and the coefficients of Kendall's concordance were 0.510 and 0.309,respectively(P<0.05).Conclusion This study uses two rounds of Delphi method to determine the issues included in the Guidelines for Preventive Treatment of Diseases in in Endometriosis,laying a solid foundation for the subsequent development of the guidelines.

Objective To observe the effects of Shenfu Injection on ferroptosis-related factors and oxidative stress-related indexes in rat cardiomyocytes treated with isoproterenol;To explore its mechanism in treating chronic heart failure.Methods Isoproterenol was used to induce rat H9c2 cardiomyocyte injury.The cells were divided into normal group,model group,Shenfu Injection group and Ferrostatin-1 group,and treated with corresponding intervention.Transmission electron microscopy was used to observe the ultrastructure of cellular mitochondria,ferrous ion fluorescent probe was used to detect Fe2+content in cells,flow cytometry was used to detect intracellular contents of ROS and Lipid-ROS;colorimetry was used to detect the contents of MDA,GSH,SOD and GSH-Px in cells;Western blot and RT-qPCR were used to detect the protein and mRNA expressions of GPX4,FTH1,SLC7A11,p53,COX2 and Nrf2 in cells.Results Compared with the normal group,the survival rate of H9c2 cells in the model group was significantly reduced(P<0.01),with cell swelling and rupture,mitochondrial shrinkage,decreased quantity and disordered arrangement,more damaged mitochondria,the contents of Fe2+,ROS,Lipid-ROS and MDA in cells significantly increased(P<0.01),while the contents of GSH,SOD and GSH-Px significantly decreased(P<0.01),the expressions of p53,COX2 protein and mRNA significantly increased(P<0.01),the expressions of GPX4,FTH1,SLC7A11 and Nrf2 protein and mRNA significantly decreased(P<0.01).Compared with the model group,the survival rates of H9c2 cells in Shenfu Injection group and Ferrostatin-1 group significantly increased(P<0.01),there was a larger number of normal mitochondria and a more complete structure,the contents of Fe2+,ROS,Lipid-ROS and MDA in cells were significantly decreased(P<0.01),while the contents of GSH,SOD and GSH-Px were significantly increased(P<0.05,P<0.01),the expressions of p53,COX2 protein and mRNA were significantly decreased(P<0.05,P<0.01),while the expressions of GPX4,FTH1,SLC7A11 and Nrf2 protein and mRNA significantly increased(P<0.01).Conclusion Shenfu Injection can reduce p53 expression,weaken its inhibitory effect on SLC7A11,thereby promoting GPX4 expression,inhibiting ferroptosis,reducing lipid peroxide accumulation,increasing cellular antioxidant capacity,and alleviating myocardial cell oxidative damage.

Objective To investigate the relationship of serum levels of neurofilament light chain protein(NFL)and chemerin with cerebral ischemia after interventional therapy in elderly patients with unruptured intracranial aneurysms.Methods A total of 258 patients with unruptured in-tracranial aneurysms undergoing stent-assisted coil embolization in our hospital from January 2020 to January 2024 were enrolled.They were divided into a cerebral ischemia group(52 cases)and a non-cerebral ischemia group(206 cases).The serum NFL and chemerin levels were detected.Multivariate logistic regression analysis was conducted to analyze the risk factors for cerebral is-chemia in the patients after interventional surgery.Results The cerebral ischemia group had sig-nificantly higher ratio of implantation of 3 stents,larger diameter of aneurysms,increased levels of NFL and chemerin before operation,10 min from the start of operation and 24 h after operation,and longer operation time than the non-cerebral ischemia group(P＜0.05,P＜0.01).Larger aneu-rysm diameter,longer operation time,and higher NFL and chemerin levels were the risk factors for cerebral ischemia in patients with unruptured intracranial aneurysm after interventional sur-gery(P＜0.05,P＜0.01).The AUC value of aneurysm diameter,operation time,NFL and chemerin,and combination of these indicators in predicting cerebral ischemia in patients with un-ruptured intracranial aneurysm after interventional surgery was 0.772,0.794,0.826,0.837,and 0.920,respectively,with that of the combination higher than that of each indicator alone(P＜0.05).Conclusion For the elderly patients with unruptured intracranial aneurysms,the increases of serum NFL and chemerin levels are associated with cerebral ischemia after stent-assisted coil embolization,which can predict the risk of cerebral ischemia after interventional therapy.