Objective To develop albumin-binding indocyanine green (ICG) and assess its potential for near-infrared fluorescence imaging and intraoperative navigation in lung cancer. Methods ABD-tri was recombinantly expressed by genetic engineering. Its albumin-binding capability was determined using size-exclusion chromatography, and its albumin-dependent binding to lung cancer cells was evaluated by flow cytometry. ICG was conjugated to ABD-tri to generate the fluorescent probe ABD-tri-ICG. The potential of ABD-tri-ICG for near-infrared fluorescence imaging and imaging-guided tumor resection was evaluated in mice bearing subcutaneous tumor grafts of lung cancer. Results ABD-tri was highly expressed in Escherichia coli (E. coli) and was purified to homogeneity via a simple affinity chromatography. ABD-tri bound both human and murine serum albumin, contributing to its binding to lung cancer cells. ICG was effectively conjugated to ABD-tri to produce the fluorescence probe ABD-tri-ICG after mixing and incubation at room temperature for 1 h. In mice bearing lung cancer tumor grafts, intravenously injected ABD-tri-ICG enabled clear visualization of tumors with diameters ranging from 5 to 7 mm within 0.5-24 h post-injection. The tumor grafts were resected under the guidance of ABD-tri-ICG-mediated near-infrared fluorescence imaging. Conclusion Intravenous injection of ABD-tri-ICG allows rapid and sustained visualization of lung cancer tumor grafts and enables intraoperative navigation in mice, warranting further evaluation on the clinical translation of ABD-tri-ICG.

Objective:To investigate the value of midtreatment 18F-FDG PET/CT metabolic parameters for predicting the pathological response in patients with locally advanced gastric cancer (LAGC) after neoadjuvant immunochemotherapy (NICT). Methods:Twenty-five LAGC patients (19 males, 6 females, age: (64.8±8.6) years) who underwent 18F-FDG PET/CT after NICT in Henan Cancer Hospital from August 2019 to June 2024 were retrospectively analyzed. The lesion′s ROI was delineated, then the SUV max and metabolic tumor volume (MTV) were measured, and the SUV max was divided by SUV mean of the descending aorta to obtain the tumor-to-background ratio (TBR). Patients underwent surgery after PET/CT imaging. Based on the tumor regression grade (TRG) system by the American Joint Committee on Cancer (AJCC) criteria on surgical specimen, patients were divided into responders (TRG0+ 1) and non-responders (TRG2+ 3). Independent-sample t test, Mann-Whitney U test, one-way analysis of variance, and Kruskal-Wallis rank-sum test were used to compare the differences of data. The predictive efficacy of PET/CT metabolic parameters was assessed by the ROC curve analysis. Results:Postsurgical pathology showed that 9 patients were responders and 16 were non-responders. The SUV max (3.10±1.95) and TBR (2.44±1.54) of primary lesions in responders were lower than those in non-responders (7.40±4.68, 5.85±3.74; t values: -2.61, -2.59, both P<0.05), while the MTV of primary tumors and short diameter and metabolic parameters of positive lymph nodes were not significantly different between those 2 groups ( t=-1.50, Z values: -1.09 to -0.75, all P>0.05). No significant relation was found between PET/CT parameters and pathological differentiation or Lauren classification, or other pathological features ( t values: -1.55 to 1.38, Z values: -1.84 to 0, F values: 0.12-2.43, H values: 0.13-0.98, all P>0.05). ROC curve showed that the cut-off value of SUV max for predicting postoperative TRG was 5.40, and the AUC reached 0.77 (95% CI: 0.56-0.91), with the sensitivity and specificity of 9/16, 9/9, respectively. With TBR=3.54 as the cut-off value, its AUC reached 0.77 (95% CI: 0.56-0.91), and the sensitivity and specificity were 11/16, 8/9, respectively. The sensitivity and specificity of PET/CT for predicting lymph node positivity of patients were 8/12 and 13/13, respectively. Conclusion:Interim 18F-FDG PET/CT metabolic parameters can accurately predict the pathological response of LAGC patients after NICT.

Objective:To investigate the effects of Vibrio vulnificus ( Vv) quorum-sensing protein LuxS on the homeostasis of pulmonary innate immune cells in sepsis-induced acute lung injury. Methods:This study constructed luxS knockout and complemented Vv strains. The time required for wild type, luxS knockout, and complemented Vv strains to grow to an absorbance of 600 nm in liquid medium was measured using a spectrophotometer. Iron-overloaded mice were intraperitoneally infected with 1×10 5 CFU of the above three kinds of Vv strains, respectively. Clinical scoring for sepsis-induced dyspnea was used to evaluate the respiratory quality in mice. At 7 h after infection, the pathological changes in lung tissues were observed by HE staining; the bacterial loads in lung tissues were measured; the single-cell suspension of lung tissues was analyzed by flow cytometry. Uniform manifold approximation and projection (UMAP) was used to reduce the dimension of the distribution of CD45 + immune cells in lung tissues of mice in the PBS control group and infection groups with different strains. The frequency and absolute number of innate immune cells in lung tissues were analyzed by multicolor flow cytometry. One-way analysis of variance and t test were used for statistical analysis. Results:There was no significant difference in the growth rate of wild type, luxS knockout, and complemented Vv strains in liquid medium. Compared with the mice infected with the wild type or complemented strain, the mice infected with the luxS knockout strain exhibited overall alleviated respiratory difficulty, decreased inflammatory cell infiltration in lung tissues, and reduced bacterial load in lung tissues ( P<0.05). Besides, there was no significant difference in clinical respiratory scores, inflammatory cell infiltration, or bacterial loads between the mice infected with the complemented strain and wild type strain. UMAP analysis showed that compared with the mice infected with the luxS knockout strain, the mice infected with the wild type or complemented strain showed increased proportions of neutrophils and eosinophils in lung tissues. Results of multicolor flow cytometry analysis further verified that the proportions of neutrophils and eosinophils were significantly lower in the mice infected with the luxS knockout strain than in the mice infected with wild type or complemented strain ( P<0.01, P<0.000 1), while the proportion of alveolar macrophages was significantly higher as compared with that in the mice infected with wild type or complemented strain ( P<0.01). Conclusion:During Vv infection, LuxS may promote acute lung injury by affecting the homeostasis of neutrophils, eosinophils and resident macrophages in lung tissues.

Objective:To explore the application of Symptom Checklist-90 (SCL-90) combined with the Eysenck Personality Questionnaire (EPQ) scors in diagnosis of mental disorders.Methods:This was a cross-sectional study. A total of 2 569 psychiatric outpatients aged 18-35 years who visited the Mental Health Center of Tongji Hospital from 2010-2020 were included in the study. Patients were diagnosed according the International Classification of Diseases 10th Edition (ICD-10). The psychiatric diagnoses included depressive disorders, anxiety disorders, sleep disorders, bipolar disorder, schizophrenia, stress-related and adjustment disorders, and obsessive-compulsive disorder. The diagnostic value of SCL-90 and EPQ scores for psychiatric disorders of patients was examined with univariate multivariate logistic regression analysis, and evaluated with ten-fold cross-validation, and receiver operating characteristic (ROC) curves.Results:Among the subjects, 921 were male (35.9%) and 1 648 were female (64.1%), with a mean age of (26.83±4.59) years.The main mental disorders were depressive disorders (42.1%, 1 081/2 569) and anxiety disorders (31.4%, 806/2 569). Stepwise logistic regression analysis showed that the highest diagnostic efficacy was for sleep disorders [area under the curve ( AUC)=0.795], significantly with obsessive-compulsive, depression, and anxiety factors of the SCL-90 (all P<0.05); followed by depressive disorders ( AUC=0.751), significantly with the female gender, depression, anxiety, and hostility factors of the SCL-90, and the introversion-extroversion factor of the EPQ (all P<0.05). There were moderate diagnostic efficacy for bipolar disorder ( AUC=0.712) and stress-related disorders ( AUC=0.703), and relatively poor diagnostic performance for anxiety disorders and obsessive-compulsive disorder ( AUC=0.702, 0.661). Conclusion:The combination of SCL-90 and EPQ demonstrates moderate to high diagnostic efficacy for common psychiatric disorders, indicating that it may be used in clinical mental health assessments.

ObjectiveTo investigate the possible mechanism by which Zhiqiao Gancao Decoction （枳壳甘草汤， ZGD） delays intervertebral disc degeneration （IDD） based on the Hippo-yes-associated protein （YAP）/transcriptional co-activator with PDZ-binding motif （TAZ） signaling pathway. MethodsA total of 50 SD rats were randomly divided into sham surgery group， model group， low-dose ZGD group， high-dose ZGD group， and high-dose ZGD + inhibitor group， with 10 rats in each group. In the sham surgery group， the rats were pierced in the skin and muscle at the Co6/7/8 segments of the tail with a 21G needle （depth approximately 2 mm） without damaging the intervertebral disc. In the other groups， rats were injected with a 21G needle at the Co6/7/8 segments of the tail to establish an IDD model by piercing the tail intervertebral disc 5 mm. One week after modeling， rats in the low-dose and high-dose ZGD groups were given 6.24 and 12.24 g/（kg·d） of the decoction via gastric gavage， respectively. The high-dose ZGD + inhibitor group was given 12.24 g/（kg·d） of the decoction and an intraperitoneal injection of YAP/TAZ inhibitor Verteporfin 10 mg/kg. The sham surgery and model groups were given 5 ml/（kg·d） of normal saline via gavage. The gavage was given once a day， and the intraperitoneal injection was given every other day. After 4 weeks of continuous intervention， the pathological changes of the tail intervertebral discs were observed using HE staining， Oil Red O-Green staining， and Toluidine Blue staining. Immunohistochemistry was used to detect the expression of aggrecan and MMP3 in the nucleus pulposus. TUNEL fluorescence staining was performed to detect apoptosis in the nucleus pulposus， and the apoptosis rate was calculated. Western blot was used to detect the Hippo-YAP/TAZ signaling pathway， including YAP， phosphorylated YAP （p-YAP）， phosphorylated MST1/2 （p-MST1/2）， phosphorylated TAZ （p-TAZ） and apoptosis-related proteins， such as Cleaved Caspase 3， P53， Bcl-2 and Bax. ResultsCompared with sham surgery group， the rats in the model group showed significant degenerative changes in the intervertebral disc. The levels of aggrecan， Bcl-2， and YAP proteins in the nucleus pulposus decreased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate increased （P < 0.01）. Compared with the model group， the drug intervention groups showed partial recovery in intervertebral disc degeneration. The levels of aggrecan， Bcl-2， and YAP proteins increased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate decreased （P＜0.05 or P＜0.01）. The high-dose ZGD group showed more significant recovery in intervertebral disc degeneration compared to the low-dose ZGD group， with a decrease in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and an increase in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. Compared with the high-dose ZGD group， the high-dose ZGD + inhibitor group showed a reduced recovery in intervertebral disc degeneration， with an increase in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and a decrease in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. ConclusionZGD may delay intervertebral disc degeneration by inhibiting the phosphorylation of YAP in the nucleus pulposus， maintaining the function of the Hippo-YAP/TAZ signaling pathway， and reducing apoptosis of nucleus pulposus cells.

ObjectiveTo explore the effect of timosaponin BⅡ （TBⅡ） combined with icariin （ICA） on osteoclast （OC）-osteoblast （OB） coupling and decipher the mechanism from the cellular level. MethodsThe cell counting kit-8 （CCK-8） was used to assess the effects of different concentrations of TBⅡ and different concentrations of TBⅡ+ICA on the growth of RAW264.7 cells. Soluble receptor activator of nuclear factor-κB ligand （sRANKL） was used to induce the differentiation of RAW264.7 pre-osteoclasts into osteoclasts. The cells were allocated into sRANKL， TBⅡ （1， 5， 10 μmol·L^-1）， and TBⅡ+ICA groups. Tartrate-resistant acid phosphatase staining was performed to assess the effects of TBⅡ and TBⅡ+ICA on osteoclast differentiation. Real-time quantitative polymerase chain reaction （Real-time PCR） was conducted to examine the effects of TBⅡ+ICA on the expression of key genes involved in osteoclast differentiation and osteoclast-derived coupling factors. The osteogenic differentiation conditioned medium mixed with osteoclast supernatant was used to induce osteogenic differentiation of MC3T3-E1 cells. Alkaline phosphatase staining and alizarin red S staining were employed to determine the effect of TBⅡ+ICA on osteogenic differentiation. Real-time PCR was employed to evaluate the effects of conditioned medium on key genes involved in osteogenic differentiation. ResultsTBⅡ at 1， 5， 10 μmol·L^-1 had no significant effect on the cell survival rate. Compared with the sRANKL group， TBⅡ inhibited osteoclast differentiation in a dose-dependent manner and achieved the best effect at 10 μmol·L^-1 （P<0.01）. Compared with the sRANKL group， different concentrations of TBⅡ down-regulated the mRNA levels of osteoclast differentiation-related genes c-Fos， RANK， and RANKL （P<0.05）. None of 10 μmol·L^-1 TBⅡ， 10 μmol·L^-1 TBⅡ+10^-4 μmol·L^-1 ICA， or 10 μmol·L^-1 TBⅡ+10^-3 μmol·L^-1 ICA affected the viability of RAW264.7 cells. TBⅡ and/or ICA inhibited osteoclast differentiation （P<0.01）， and TBⅡ + ICA had the best effect （P<0.01）. Compared with the sRANKL group， TBⅡ and/or ICA down-regulated the mRNA levels of c-Fos， RANK， and RANKL （P<0.05）. The single application of TBⅡ and ICA had no significant effect on the mRNA levels of Wnt10b， Cthrc1， and C3a， while TBⅡ+ICA exerted up-regulating effects （P<0.05）. Compared with those in the blank group， the bone differentiation and mineralization abilities of the normal osteogenic induction group and each osteogenic induction + osteoclast supernatant group were improved （P<0.01）. Compared with the blank group， the normal osteogenic induction group and the osteogenic induction + osteoclast supernatant group showed up-regulated mRNA levels of Runx2 and OCN （P<0.01）. ConclusionTBⅡ+ICA can inhibit osteoclast differentiation， maintain the normal osteoclast-osteoblast coupling， and promote osteogenic differentiation.

Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia,which long-term loss of control can lead to complications of blood vessels of heart,renal and other multi-system,and even threaten the patient's life.Monitoring for blood glucose is crucial for adjusting treatment and preventing complications.Traditional invasive glucose monitoring technology requires frequent blood collection,which not only leads to significant pain in patients,but also poses the risk of infection at the puncture site,coupled with the reduced compliance brought about by cumbersome operation,which seriously restricts the effectiveness and continuity of blood glucose management.The non-invasive monitoring technique for blood glucose can enhance frequency of monitoring,and comfort level through optical method,biosensing method,etc.,which has key values in optimizing glycemic control,reducing risk of complications,and decreasing medical cost.It is becoming a hot point of research.This review summarized a noninvasive monitoring technique system included sample analysis method,optical method and physiological process-based method,which analyzed principles,advantages,and limitations of its development of each detection method.The review also concluded the challenges of noninvasive monitoring technique for blood glucose in some aspects included overcoming individual differences,enhancing precision of measurement,and improving accuracy and stability.In addition,it proposed some developing directions of noninvasive monitoring technique in future,such as continuous monitoring equipment with low cost,establishment of standardized database,and individual validation,so as to promote implementation of noninvasive monitoring technique for blood glucose,and realize accurate management for diabetes mellitus.

BACKGROUND:Patch clamp technique has been developed for more than 40 years as the"gold standard"for the study of ion channels.However,the research content of scientific research institutions is relatively independent,and the existing research results are not systematically summarized,which leads to the phenomenon of high repeatability and weak innovation in the existing research.Therefore,it is urgent to make a comprehensive review of patch clamp technology to clarify the current research status,hot spots,and future development direction.OBJECTIVE:To summarize the research status and development trend of patch clamp technique in recent 10 years.METHODS:Publications on patch clamp technology from 2013 to 2023 were collected using the Web of Science core collection database.CiteSpace and VOSviewer software were used to quantify the number of publications and analyze the network of literature entries,including countries,institutions,journals,authors,keywords,highly cited literature,and co-cited references.RESULTS AND CONCLUSION:(1)In recent 10 years,the research in the field of patch clamp technology has gradually entered a stage of stable development.(2)China and the United States are the leading countries in this regard.The Chinese Academy of Sciences is an institution with core influence.Journal of Neuroscience is the main publication.Park,Won Sun team(Jeonbuk National University)and Chu,Li team(Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease)have made outstanding contributions in this field,but there is less collaboration and communication between the teams and no network cooperation model has been formed.(3)Patch clamp technology is mainly used in the electrophysiological characteristics of the nervous system and the pathological mechanism of the disease,which is the focus of researchers'continuous attention.(4)In the study of electrophysiological characteristics of cardiovascular system and its pathological mechanism,the electrophysiological characteristics of primary cardiomyocytes and induced pluripotent stem cell-derived cardiomyocytes and the pathological mechanism of atrial fibrillation,cardiotoxicity,sudden cardiac death,hypertension and other cardiovascular diseases have been the focus of research in recent years.(5)In the application of patch clamp technology combined with other biotechnology,it will be an important research direction to focus on the cross fusion with optogenetics,two-photon calcium imaging and other technologies.(6)In the research of drug screening and identification of therapeutic targets,especially the research of patch clamp technology and traditional Chinese medicine compound,it will become a great help in the future research of component traditional Chinese medicine.

Objective:To identify the core symptoms of prostate cancer patients with endocrine therapy by constructed the symptom network, and provide a basis for precise intervention of symptoms management.Methods:In a cross-sectional study, we conveniently sampled patients receiving endocrine therapy for prostate cancer at Fudan University Shanghai Cancer Center between March and August 2018. The Expanded Prostate cancer Index Composite 26-item version (EPIC-26) and the Hospital Anxiety and Depression Scale (HADS) were used to assess symptoms.Symptom networks were constructed, and network indexes and the accuracy and stability of core symptoms were computed based on various packages of R4.3.1. Subgroup network comparison tests were conducted by Prostate-specific antigen (PSA) level, stratifying patients into PSA>0.2 ng/ml and PSA≤0.2 ng/ml groups.Results:A total of 270 questionnaires were distributed, and 261 valid questionnaires were returned, yielding a valid response rate of 96.7%. The included patients were aged 43 - 87(67.81 ± 8.14) years. Symptom network analysis revealed that the core symptom in patients undergoing endocrine therapy for prostate cancer was endocrine disorder ( rs = 1.86, rc = 0.048). However, in the population with PSA ≤ 0.2 ng/ml, depression ( rs = 1.80, rc = 0.028) occupied a more central position. There was no statistically significant difference in the network structure among patients with different PSA levels ( M = 0.294, P = 0.100). But the difference in network strength was statistically significant ( S = 1.15, P<0.05). The strongest associations were observed between depression and anxiety, as well as between endocrine disorder anddepression.The network demonstrated good stability and accuracy,indicating a reliable network model. Conclusions:Endocrine disorder is the core symptom in patients undergoing endocrine therapy for prostate cancer, serving as a critical target for intervention. Special attention should be given to the interconnected effects between endocrine disorder and depression. For the population with PSA ≤ 0.2 ng/ml, negative emotions such as depression still require ongoing focus. In the future, comprehensive interventions centered on psychological support and endocrine symptom management should be implemented for prostate cancer patients receiving endocrine therapy.

Objective:To explore the value of Alberta stroke program early CT Score (ASPECTS) regional net water intake (NWU) based on plain CT in evaluating the neurological outcome of patients with acute large vessel occlusive stroke (ALVOS) after mechanical thrombectomy.Methods:The study was a prospective cross-sectional study. The clinical and imaging data of patients with ALVOS who underwent mechanical thrombectomy in the 904 Hospital of the PLA Joint Service Support Force from June 2022 to June 2024 were prospectively collected. Clinical data analysis included age, gender distribution, National Institutes of Health Stroke Scale (NIHSS) score and Glasgow Coma Scale (GCS) score at admission. All patients underwent plain CT and CT angiography (CTA). Automated processing software quantified ischemic brain edema by calculating ASPECTS and measuring the ASPECTS regional NWU rate (CT-ASPECTS-NWU) based on plain CT. Cerebral collateral circulation was assessed using CTA images. According to the modified Rankin Scale score of patients with mechanical thrombectomy 90 days after the telephone follow-up, 0-2 points were defined as good neurological outcome, and 3-6 points were defined as poor neurological outcome. Independent samples t test, Mann-Whitney U test and χ2 test were used to analyze the differences of clinical and imaging indicators between patients with good and poor neurological outcome, indicators with statistically significant differences were included in multivariate logistic regression analysis to screen out the independent influencing factors that predicted the neurological outcome of patients with ALVOS after mechanical thrombectomys. The efficacy of related indicators to predict neurological outcomes after mechanical thrombectomy in patients with ALVOS was evaluated using receiver operating characteristic (ROC) curve analysis, with the area under the curve (AUC) calculated. Results:A total of 122 patients with ALVOS were included, including 101 patients with good neurological outcome and 21 patients with poor neurological outcome after mechanical thrombectomy. There were statistically significant differences in preoperative GCS score, collateral circulation status, NIHSS score at admission, preoperative ASPECTS and CT-ASPECTS-NWU between patients with good neurological outcome and patients with poor neurological outcome ( P<0.05). Multivariate logistic regression analysis showed that the status of collateral circulation ( OR=3.450, 95% CI 1.158-10.277, P=0.026), preoperative ASPECTS ( OR=0.510, 95% CI 0.274-0.952, P=0.034) and CT-ASPECTS-NWU ( OR=2.131, 95% CI 1.301-3.493, P=0.003) were independent predictors of neurological outcome in patients with ALVOS after mechanical thrombectomy. ROC curve analysis showed that CT-ASPECTS-NWU had the highest predictive value, with an AUC of 0.881, a sensitivity of 85.7%, a specificity of 85.1%, and an optimal cutoff value of 7.55. Conclusion:CT-ASPECTS-NWU demonstrates high diagnostic value in evaluating the neurological outcome of patients with ALVOS after mechanical thrombectomy, and can provide an objective imaging biomarker to guide clinical decision-making.