Objective To investigate the anti-intrahepatic cholangiocarcinoma （ICC） activity and mechanism of 2-heptyl-3-hydroxy-4（1H）-quinolone （PQS）, a secondary metabolite of polar marine microorganisms. Methods Patient-derived organoid （PDO） models were established using intrahepatic cholangiocarcinoma （ICC） tumor tissues obtained from Renji Hospital, Shanghai Jiao Tong University School of Medicine. Hematoxylin and eosin （HE） staining was performed to assess the histomorphological characteristics of both patient ICC tissues and corresponding PDOs. Immunohistochemistry （IHC） was employed to evaluate CYP3a expression in patient ICC tissues and PDOs. The antiproliferative activity of PQS against stably passaged PDOs was determined using an adenosine triphosphate （ATP）-based bioluminescence assay, and dose-response curves were fitted to calculate the half-maximal inhibitory concentration （IC₅₀） for assessing the anti-ICC efficacy of PQS. In the human intrahepatic cholangiocarcinoma RBE cell model, the effects of PQS on RBE cell proliferation were evaluated by the cell counting kit-8 （CCK-8） assay; colony formation capacity was assessed by the plate colony formation assay; cell cycle distribution and apoptosis were analyzed by flow cytometry; and the protein expression levels of cyclin-dependent kinase 2（CDK2）, CDK4, RelA（p65）, and nuclear factor-κB1（p50） were detected by Western blotting. Results Two ICC PDO models were successfully established. Histomorphological observation revealed that the PDO tissues after serial passaging exhibited morphological features essentially consistent with the corresponding patient ICC tissues, both presenting as cystic vesicle-like structures. Immunohistochemical analysis demonstrated that CYP3a was expressed in both PDO tissues and patient ICC tissues. ATP-based bioluminescence assay results indicated that PQS effectively suppressed ATP content in PDO tissues, with a fitted dose-response curve yielding an IC₅₀ value of 2.49 µmol/L. In the RBE cell model, PQS inhibited RBE cell viability in a concentration-dependent manner, and the fitted dose-response curve yielded an IC₅₀ value of 1.05 µmol/L. Furthermore, PQS at concentrations of 1, 2, and 4 µmol/L significantly suppressed colony formation of RBE cells, arrested the cell cycle at the S phase, induced apoptosis, and downregulated the expression of proteins associated with the NF-κB signaling pathway. Conclusion ICC PDO models were successfully established, confirming the anti-ICC activity of PQS. PQS inhibited RBE cell proliferation, potentially via the NF-κB signaling pathway, by arresting the cell cycle at the S phase and inducing apoptosis of RBE cells

Objective To investigate the anti-intrahepatic cholangiocarcinoma （ICC） activity and mechanism of 2-heptyl-3-hydroxy-4（1H）-quinolone （PQS）, a secondary metabolite of polar marine microorganisms. Methods Patient-derived organoid （PDO） models were established using intrahepatic cholangiocarcinoma （ICC） tumor tissues obtained from Renji Hospital, Shanghai Jiao Tong University School of Medicine. Hematoxylin and eosin （HE） staining was performed to assess the histomorphological characteristics of both patient ICC tissues and corresponding PDOs. Immunohistochemistry （IHC） was employed to evaluate CYP3a expression in patient ICC tissues and PDOs. The antiproliferative activity of PQS against stably passaged PDOs was determined using an adenosine triphosphate （ATP）-based bioluminescence assay, and dose-response curves were fitted to calculate the half-maximal inhibitory concentration （IC₅₀） for assessing the anti-ICC efficacy of PQS. In the human intrahepatic cholangiocarcinoma RBE cell model, the effects of PQS on RBE cell proliferation were evaluated by the cell counting kit-8 （CCK-8） assay; colony formation capacity was assessed by the plate colony formation assay; cell cycle distribution and apoptosis were analyzed by flow cytometry; and the protein expression levels of cyclin-dependent kinase 2（CDK2）, CDK4, RelA（p65）, and nuclear factor-κB1（p50） were detected by Western blotting. Results Two ICC PDO models were successfully established. Histomorphological observation revealed that the PDO tissues after serial passaging exhibited morphological features essentially consistent with the corresponding patient ICC tissues, both presenting as cystic vesicle-like structures. Immunohistochemical analysis demonstrated that CYP3a was expressed in both PDO tissues and patient ICC tissues. ATP-based bioluminescence assay results indicated that PQS effectively suppressed ATP content in PDO tissues, with a fitted dose-response curve yielding an IC₅₀ value of 2.49 µmol/L. In the RBE cell model, PQS inhibited RBE cell viability in a concentration-dependent manner, and the fitted dose-response curve yielded an IC₅₀ value of 1.05 µmol/L. Furthermore, PQS at concentrations of 1, 2, and 4 µmol/L significantly suppressed colony formation of RBE cells, arrested the cell cycle at the S phase, induced apoptosis, and downregulated the expression of proteins associated with the NF-κB signaling pathway. Conclusion ICC PDO models were successfully established, confirming the anti-ICC activity of PQS. PQS inhibited RBE cell proliferation, potentially via the NF-κB signaling pathway, by arresting the cell cycle at the S phase and inducing apoptosis of RBE cells

To summarize the clinical characteristics, antibody spectrum and neuroelectrophysiological features of autoimmune nodopathy(AN), and to explore the phenotypic differences among different antibody-positive subgroups.

With the continuous deepening of the concept of precision diagnosis and treatment for lung cancer, how to achieve higher efficiency and accuracy in the screening, diagnosis, and treatment pathways in clinical practice has become an important issue that urgently needs to be overcome. The current clinical difficulty lies in the fact that despite continuous advancements in imaging and molecular diagnostic technologies, there are still limitations in manual efficiency and subjective experience when it comes to massive data analysis and multi-scale feature extraction. Artificial intelligence (AI), especially algorithm systems based on deep learning, is an innovative technology capable of deeply empowering medical big data. This method utilizes algorithms such as convolutional neural networks, combined with radiomics, pathomics, and multi-modal data fusion analysis, demonstrating immense potential in early precise detection and benign-malignant differentiation of pulmonary nodules, digital pathological subtype recognition and non-invasive prediction of driver genes, precise 3D surgical planning and automatic delineation of radiotherapy target volumes, as well as dynamic risk warning during follow-up. This innovative technology provides a brand-new solution for realizing intelligent and individualized lung cancer diagnosis and treatment models. This consensus, based on the latest evidence from evidence-based medicine and combined with the development trends in the AI field and real-world clinical needs, was ultimately formed by gathering the consensus opinions of multidisciplinary experts in radiology, pathology, thoracic surgery, and other fields. The main content covers the application specifications of AI in the three core scenarios of lung cancer screening, diagnosis, and treatment, the technical standards for data collection and algorithm validation, as well as the ethical and regulatory challenges faced at the current stage. It aims to clarify the applicable boundaries of AI as a clinical auxiliary decision support tool, providing scientific guidance and standardized exploration directions for peers currently engaged in or planning to carry out AI-assisted clinical diagnosis, treatment, and translation of lung cancer.

Objective: To understand the current status of psychological sub health among secondary vocational school students and explore its related factors, so as to provide a scientific basis for improving their mental health. Methods: From September to December 2024, a convenience sampling method was used to conduct a questionnaire survey among 5 141 secondary vocational school students from 16 schools across 8 provinces and municipalities (Fujian, Chongqing, Guangdong, Guangxi, Hubei, Jiangxi, Shanghai, Zhejiang). A self designed questionnaire was used to collect data on students demographic characteristics and lifestyle behaviors. The Multidimensional Sub health Questionnaire of Adolescents was adopted to assess psychological sub health status. Multivariate binary Logistic stepwise regression analysis was performed to explore the related factors of psychological sub health among secondary vocational school students. Results: The detection rate of psychological sub health among secondary vocational school students was 11.0%, with detection rates of emotional problems, conduct problems, and social adaptation difficulty being 12.3 %, 12.5%, and 9.5%, respectively. Logistic regression analysis revealed that boys and students whose fathers had an educational level of primary school or below, and junior high school, had relatively lower risks of developing psychological sub health or emotional problems, conduct problems, and social adaptation difficulty ( OR =0.55-0.64, all P <0.05). Conversely, students with urban household registration, those with left behind experience, those with poor self rated family economic status, those from other family structures, those classified as overweight and obesity, and those with sleep disorders, frequent consumption of sugar sweetened beverages, frequent consumption of takeout/delivery food, smoking, alcohol consumption, and low to moderate physical activity levels exhibited significantly higher risks across psychological sub health or emotional problems,conduct problems, and social adaptation difficulty ( OR =1.25-4.79, all P <0.05). Conclusions The psychological sub health condition of secondary vocational school students should not be neglected. Psychological sub health of secondary vocational school students is related to multiple factors such as demographic characteristics and lifestyle behaviors. Multi dimensional intervention measures should be implemented to improve their mental health.

AIM To investigate the mechanism of Jiedu Yizhi Formula on cognitive function and neuroinflammation in a mouse model of Alzheimer's disease(AD).METHODS 50 APP/PS1 double transgenic mice were randomly divided into the model group,the donepezil group,and the low-dose,moderate-dose,and high-dose Jiedu Yizhi Formula group(1.78,3.56 and 7.12 g/kg),with 10 mice in each group,in contrast to the 10 WT mice of the blank group.Following anesthesia administration and 8-week oral gavage regimen with respective drugs,all mice underwent final tissue sample collection.The mice had their learning and memory ability assessed by Morris water maze and nesting behavior scores;their pathology of brain tissue and Aβ expression observed using HE,Nissl and IHC staining;their polarization of microglia and the expression of inflammatory factors in hippocampal tissue detected by IF and ELISA;their hippocampal expression of PI3K/Akt/mTOR signaling pathway detected by RT-qPCR and Western blot.RESULTS Compared with the blank group,the model group had lower scores in total swimming distance,frequency in crossing the platform,residence time in the target quadrant,and nesting behavior scores(P＜0.05,P＜0.01);prolonged evasion latency(P＜0.01);more disorganized arrangement of pyramidal cells,solidification and deep staining,unclear demarcation,irregular cell shapes,reduction of Nyctinidia,and increased Aβ deposition in the brain tissue(P＜0.01);elevated expression of hippocampal microglia M1-type markers CD16/32 and lba-1(P＜0.01);decreased levels of M2-type marker CD206(P＜0.05);elevated levels of TNF-α and IL-1β(P＜0.01);decreased expressions of IL-13 and IL-4(P＜0.01);and decreased levels of PI3K,Akt and mTOR mRNA,and reduced p-PI3K,p-Akt and p-mTOR protein expressions(P＜0.01).Compared to the model group,the donepezil group and the Jiedu Yizhi Formula groups showed statistically significant improvements in the aforementioned indexes(P＜0.05,P＜0.01),with the magnitude of improvement being higher in the high-dose Jiedu Yizhi Formula group.CONCLUSION Jiedu Yizhi Formula suppresses microglia Ml-type polarization while enhancing M2-type polarization via activation the PI3K/Akt/mTOR signaling pathway,which subsequently reduces inflammatory cytokine secretion.This mechanism attenuates Aβ deposition in brain tissues and ameliorates cognitive dysfunction in AD mouse models.

Objective To investigate the influencing factors of the course of perioperative prophylactic antibiotics in patients undergoing total hip arthroplasty,and explore management strategies for enhancing perioperative prophylactic medication administration.Methods The clinical data for patients undergoing total hip arthroplasty at Affiliated Hospital of Chengdu University from January,2020 to September,2024 were retrospectively collected.Patients were divided into a 24 h group and a 48-72 h group based on the duration of prophylactic antibacterial therapy.The general characteristics,surgical-related indicators,preoperative and postoperative laboratory test results,and surgical outcome measures between the two groups of patients were compared.Multivariate Logistic regression analysis was performed to identify influencing factors associated with prolonged duration of prophylactic antibacterial therapy.Results A total of 126 patients who underwent total hip arthroplasty were enrolled,including 74 cases in the 24 h group and 52 cases in the 48-72 h group.Univariate analysis results showed that there were statistically significant differences in the following indicators between the two groups:surgical cause,surgical duration,intraoperative blood loss,drainage duration of plasma drainage tubes,preoperative white blood cell count,and preoperative neutrophil count(P<0.05).The results of multivariate Logistic regression analysis showed that the reason for surgery and the duration of plasma drain tube drainage were the influencing factors of antimicrobial treatment course for total hip arthroplasty(P<0.05).The results of receiver operating characteristic curve analysis showed that the prediction model(constructed based on the drainage time of plasma drainage tube)for prophylactic antimicrobial treatment course to 48-72 h was 0.721.When the drainage time of plasma drainage tubes was≥40.56 h,the risk of requiring prophylactic antimicrobial therapy for an extended course of 48-72 h increased significantly.Conclusion The patient's surgical reason and the duration of plasma drain drainage may be related to the prophylactic antimicrobial course of more than 24 hours.Clinical pharmacists may utilize this parameter as a patient-specific characteristic,with the support of information systems,the hierarchical patient management can be implemented,thereby enhancing the effectiveness of medication surveillance and progressively elevating the 24 h discontinuation rate of perioperative prophylactic antibiotics.

Objective:To explore the effects of remimazolam versus dexmedetomidine combined with spinal-epidural anesthesia in elderly patients undergoing hip replacement.Methods:A total of 100 elderly patients who needed total hip replacement in the Nanjing Lishui People′s Hospital from March 2021 to March 2023 were selected and divided into two groups by dynamic randomization, with 50 cases in each group. Both groups underwent surgery under combined spinal-epidural anesthesia. The control group was given dexmedetomidine for anesthesia, and the observation group was given remimazolam for anesthesia. The depth of sedation [eye-opening time, post anesthesia care unit (PACU) stay time, awakening time], cognitive function at different time periods [Mini-Mental State Examination (MMSE) score], inflammatory factor indexes [interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)], and hemodynamic indexes [heart rate (HR), mean arterial pressure (MAP)] were compared between the two groups.Results:The eye-opening time and PACU stay time in the observation group were shorter than those in the control group (all P<0.05), and there was no significant difference in awakening time between the two groups ( P>0.05). The MAP of both groups at post-skin incision (T 1) and completion of internal fixation (T 2) was higher than that after anesthesia induction (T 0), and decreased at the end of surgery (T 3); the HR of both groups at T 1 was lower than that at T 0, but increased at T 2, and then decreased at T 3. There were no significant differences in MAP and HR between the two groups at each time point (all P>0.05). The MMSE scores of the observation group at 1, 4, and 7 days after surgery were significantly higher than those of the control group (all P<0.05). The serum levels of IL-1β, IL-6, and TNF-α in both groups at post-anesthesia (t 1), end of surgery (t 2), and post-surgery (t 3) were significantly higher than those at 1 day before surgery (t 0), and the serum levels of IL-1β, IL-6, and TNF-α in the observation group at t 1, t 2, and t 3 were lower than those in the control group (all P<0.05). Conclusions:Both remimazolam and dexmedetomidine can effectively maintain hemodynamic stability in elderly patients undergoing hip replacement surgery, while remimazolam can more effectively shorten the time to reach the required depth of sedation, reduce the occurrence of cognitive dysfunction, and decrease the secretion of inflammatory factors.

Aim To investigate the therapeutic effect of newly formulated Tadalafil tablets on liver fibrosis in mice induced by carbon tetrachloride(CCl4)and its impact on the activation of hepatic stellate cells(HSCs).Methods Liver fibrosis model was estab-lished by intraperitoneally injecting 20％CCl4 corn oil solution twice a week for eight weeks.After four weeks of modeling,the treatment group was administered ei-ther the newly formulated Tadalafil tablets(1.0 mg·kg-1)or the Cialis(2.5 mg·kg-1)via gavage for the remaining four weeks.We assessed the effects of Tadalafil on collagen deposition,tissue structural dam-age,and HSCs activation markers in the fibrotic liver of mice using serum biochemical analysis,histopathologi-cal staining,and Western blotting following the treat-ment period.LX-2 cells were cultured and treated with tadalafil after TGF β1 stimulation,and the effects of tadalafil on LX-2 cell activation were assessed via Western blot.Results Compared to the normal mice,the model group mice exhibited a significantly higher liver-specific index,increased liver function indicators,and notable hepatocyte necrosis.Additionally,liver lobules were damaged,accompanied by severe infiltra-tion of inflammatory cells.Both smooth muscle actin(α-SMA)and fibronectin(Fn)were elevated,serving as markers of HSCs activation.As a result of treatment with the newly formulated Tadalafil tablets,liver tissue damage was significantly reduced,transaminase levels decreased,necrosis and inflammatory cell infiltration were reduced,and collagen fiber deposition was allevia-ted,and α-SMA and Fn expression was reduced.It was worth noting that low-dose newly formulated Tadalafil tablets were found to be as effective as high-dose Cia-lis.In a cellular model,Tadalafil significantly inhibited the activation of LX-2 cells and reduced the expression of proteins related to cell activation.Conclusions The newly formulated Tadalafil tablets can significantly inhibit HSCs activation,reduce extracellular matrix(ECM)deposition,improve liver fibrosis and liver function damage caused by CCl4.This new formulation offers a significant advantage over Cialis in terms of ef-fectiveness,with a lower effective dose.

Objective:To investigate the change trend of hepatectomy for hepatocellular carcinoma and efficacy of fluorescent laparoscopic hepatectomy in a single center from 2014?2023.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 17 232 patients of hepatocellular carcinoma who were admitted to Zhongshan Hospital of Fudan University from January 2014 to December 2023 were collected. There were 14 404 males and 2 828 females, aged 58(range, 11?94)years. Observation indicators: (1) change trend of hepatectomy for hepatocellular carcinoma and application of fluorescent laparoscopy in 2014?2023; (2) propensity score matching between patients undergoing fluorescent and conventional laparoscopic hepatectomy; (3) intraoperative and postoperative conditions of patients in the fluorescent laparoscopy group and the conventional laparoscopy group after propensity score matching. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the nonparametic rank sum test. Propensity score matching was performed using the 1∶3 nearest neighbor matching method, with the caliper value of 0.01. Results:(1) Change trend of hepatectomy for hepatocellular carcinoma and application of fluorescent laparoscopy in 2014-2023. Among 17 232 patients of hepatocellular carcinoma, 4 074 cases underwent laparoscopic surgery, and 13 158 cases underwent open surgery or conversion from laparoscopic to open surgery. From 2014 to 2023, the proportions of laparos-copic surgery in hepatectomy were 8.993%(117/1 301), 6.804%(99/1 455), 9.379%(145/1 546), 17.511%(287/1 639), 23.828%(427/1 792), 24.572%(459/1 868), 29.662%(544/1 834), 31.568%(584/1 850), 38.080%(599/1 573), and 34.246%(813/2 374), respectively. The proportions of Grade Ⅲ surgery in laparoscopic hepatectomy were 11.966%(14/117), 7.071%(7/99), 12.414%(18/145), 21.254%(61/287), 28.337%(121/427), 27.887%(128/459), 34.375%(187/544), 34.644%(214/584), 35.726%(214/599), and 42.681%(347/813), respectively. From 2016 to 2023, the proportions of the application of fluorescent laparoscopy in laparoscopic hepatectomy were 2.069%(3/145), 5.923%(17/287), 8.431%(36/427), 10.022%(46/459), 17.647%(96/544), 24.829%(145/584), 9.182%(55/599), and 12.915%(105/813), respectively. (2) Propensity score matching between patients undergoing fluorescent and conventional laparoscopic hepatectomy. Among the 4 074 patients who underwent laparoscopic liver resection, 503 cases using fluorescent laparoscopy were assigned to the fluorescent laparoscopy group, 3 571 cases using conventional laparoscopy were assigned to the conventional laparoscopy group. A total of 1 794 patients were successfully matched, with 483 cases in the fluorescent laparoscopy group and 1 311 cases in the conventional laparoscopy group. After propensity score matching, the confounding biases of the maximum tumor diameter and the year of surgery were eliminated, and the two groups were comparable. (3) Intraoperative and postoperative conditions of patients in the fluorescent laparoscopy group and the conventional laparoscopy group after propensity score matching. After propensity score matching, there was no perioperative death in either the fluorescent laparoscopy group or the conventional laparoscopy group.The operation time of patients in the fluorescent laparoscopy group was 240(150,328)minutes, the portal triad clamping time was 30(15,45)minutes, the volume of intraoperative blood loss was 50(30,100)mL, the number of patients with complication 72, respectively. For patients in the conventional laparoscopy group, the above indicators were 180(131,240)minutes, 23(15,30)minutes, 55(50,100)mL, and 248, respectively. There were significant differences in the above indicators between the two groups ( Z=?7.593, ?7.372, ?4.941, χ2=3.873, P<0.05). Conclusion:The proportion and difficulty level of laparoscopic hepatectomy for hepatocellular carcinoma in Zhongshan Hospital of Fudan University have shown an upward trend during 2014?2023. Compared with conventional laparoscopy, patients undergoing fluorescent laparoscopic hepatectomy have longer operation time and portal triad clamping time, but less intraoperative blood loss and lower iproportion of complications.