Objective To explore the mechanism of Kangliu Zengxiao Jiandu Prescription(KLJD)in enhancing the efficacy of cisplatin chemotherapy in non-small cell lung cancer(NSCLC)through network pharmacology and in vivo/in vitro experiments.Methods Components of KLJD were screened via the TCMSP database to identify active components and potential targets.Lung cancer-related genes were obtained from the GeneCards and OMIM databases.GO and KEGG pathway enrichment analysis was performed on drug-disease intersection targets using the Metascape database;molecular docking was performed between core target proteins and main active components.A Lewis lung cancer mouse model was established,and intervened with KLJD and cisplatin.Organ indexes and tumor inhibition rate were counted,and Western blot and RT-PCR were used to detect the expressions of key pathway target proteins and mRNA;A549 and H1299 cells were intervened with KLJD,and Western blot was used to detect key target protein expressions.Results Network pharmacology identified 74 active components and 20 key targets of KLJD,primarily involved in biological processes such as cell proliferation and inflammatory response,and pathways in cancer and PI3K/AKT signaling pathway;molecular docking revealed stable binding between EGFR and major compounds.Animal experiments demonstrated that,compared with the model group,the KLJD group showed significantly higher tumor inhibition rate(P<0.01)and downregulation of EGFR,AKT and PI3K protein and mRNA expression in tumor tissues(P<0.05).Compared with the cisplatin group,the combination group exhibited significantly enhanced tumor inhibition rate(P<0.01),elevated thymic and splenic indices(P<0.01),and decreased EGFR,PI3K and AKT protein and mRNA expressions(P<0.01).Cell experiments showed that KLJD concentration-dependently inhibited A549 and H1299 cell proliferation(IC50:14.72 mg/mL and 14.68 mg/mL,respectively).Combined with cisplatin,KLJD synergistically down-regulated EGFR PI3K and AKT protein expressions(P<0.01).Conclusion KLJD effectively enhances cisplatin's chemotherapeutic efficacy in NSCLC by inhibiting the EGFR/PI3K/AKT pathway while improving immune organ function.Its mechanism likely involves multi-target regulation,including suppression of tumor proliferation,promotion of apoptosis,and modulation of the immune microenvironment.

Objective: Exploring the effect and mechanism of Xinyang Tablet on reduction of ferroptosis in myocardial cells from mice with chronic heart failure. Methods: Sixty C57BL/6J mice were randomly assigned to the sham, model, Xinyang Tablet low-dose (0.34 g/kg), Xinyang Tablet medium-dose (0.68 g/kg), Xinyang Tablet high-dose (1.36 g/kg), and perindopril (0.607 mg/kg) groups using a random number table method (10 mice in each group). Except for the sham group, all other groups underwent aortic arch constriction surgery to construct a chronic heart failure model. On the third day after completion of the modeling, each treatment group was administered the corresponding medication by gavage, while the sham and model groups were administered equal volumes of water by gavage once a day for eight consecutive weeks. After treatment, cardiac ultrasound was used to detect the structure and function of the mouse heart. Hematoxylin and eosin staining was used to detect pathological changes in mouse heart tissue. Masson staining was used to detect the proportion of fibrotic area of mouse heart tissue. Realtime fluorescence PCR was used to detect the mRNA expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), collagen 3α (Col3α), and myosin heavy chain 7 (MYH7) in mouse myocardial tissue. Transmission electron microscope was used to detect the ultrastructure of myocardial cell mitochondria. Reactive oxygen species (ROS) staining was used to detect the mean fluorescence intensity of ROS in myocardial tissue. Micro-determination was used to detect superoxide dismutase (SOD) activity in myocardial tissue. An immunofluorescence assay was used to detect the mean fluorescence intensity of phosphorylated histone deacetylase 2 (p-HDAC2) in myocardial cell. Western blotting was used to detect the protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), p-HDAC2, nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), glutathione peroxidase 4 (GPX4), and cystine glutamate reverse transporter (xCT) in mouse myocardial tissue. Results: Compared to the sham group, the model group showed a decrease in left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), an increase in left ventricular end-systolic diameter(LVESD) and left ventricular end-diastolic diameter (LVEDD), an increase in the proportion of cardiac fibrosis area, an increase in relative expression levels of ANP, BNP, Col3α, and MYH7 mRNA, an increase in ROS mean fluorescence intensity, a decrease in SOD activity, an increase in mean fluorescence intensity of p-HDAC2, an increase in relative expression levels of p-HDAC2 and NOX1 proteins, and a decrease in relative expression levels of Nrf2, GPX4, and xCT proteins (P<0.05). Myocardial fibrosis lesions are obvious, with disordered mitochondrial arrangement, decreased volume and shrinkage, increased membrane density, and reduced mitochondrial cristae. Compared to the model group, the LVEF and LVFS of mice in each dose group of Xinyang Tablet and the perindopril group increased, LVESD and LVEDD decreased, the proportion of fibrotic area of heart tissue decreased, the relative expression levels of ANP, BNP, Col3α, MYH7 mRNA decreased, ROS mean fluorescence intensity decreased, SOD activity increased, mean fluorescence intensity of p-HDAC2 decreased, relative expression levels of p-HDAC2 and NOX1 proteins decreased, and relative expression levels of Nrf2 and xCT proteins increased (P<0.05). Myocardial fibrosis was reduced, the mitochondrial arrangement was more regular, the mitochondria enlarged, the membrane density was reduced, and mitochondrial cristae increased. Compared to the model group, the relative expression level of the GPX4 protein in myocardial tissue increased in the Xinyang Tablet medium-, high-dose, and the perindopril groups (P<0.05). Conclusion Xinyang Tablet can improve ferroptosis and ventricular remodeling in mice with chronic heart failure by regulating the HDAC2-mediated Nrf2 antioxidant pathway.

Objective:To analyze the safety and efficacy of multi-vessel minimally invasive cardiac surgery-coronary artery bypass graft(MICS-CABG) through perioperative angiography results and complications.Methods:Clinical data of 1 073 patients who underwent multi-vessel MICS-CABG surgery at Peking University Third Hospital from December 2015 to June 2024 were collected using an ambispective cohort study. Among them, 745 were males(69.4%), with a median age of 65 years(58, 71), and a median ejection fraction of 0.66(0.56, 0.71). Double-vessel or triple-vessel lesions accounted for 932 cases(86.9%), while left main lesions were present in 449 cases(41.8%). The primary outcome was the evaluation of graft patency based on perioperative angiography or coronary artery computed tomography angiography results, while major cardiovascular adverse events during the perioperative period, surgical complications, and other surgical information were secondary outcomes. The clinical efficacy of multi-vessel MICS-CABG was evaluated.Results:In this study, the median number of grafts was 3, and complete revascularization was performed in 1 006 cases(93.8%); total arterial revascularization was performed in 308 cases(28.6%). Perioperative mortality was 11 cases(1.0%), and the main adverse cardiovascular and cerebrovascular events(MACCE) was 50 cases(4.8%). Three cases(0.3%) had poor wound healing, and 79 patients(7.4%) required transfusion. Postoperative coronary angiography was performed in 907 patients(84.5%) and coronary CTA was performed in 52 patients(4.8%), for an overall review rate of 89.4%(959/1073). The overall patency rate of the bridge vessel was 96.9%, and the patency rate of the left internal mammary artery was 98.2%.Conclusion:Multi-vessel MICS-CABG demonstrates excellent perioperative safety and is capable of achieving complete revascularization for the 3 regions of the heart. The quality of the anastomosis and the postoperative patency rate of the grafts is satisfactory.

Objective To explore the mechanism of Kangliu Zengxiao Jiandu Prescription(KLJD)in enhancing the efficacy of cisplatin chemotherapy in non-small cell lung cancer(NSCLC)through network pharmacology and in vivo/in vitro experiments.Methods Components of KLJD were screened via the TCMSP database to identify active components and potential targets.Lung cancer-related genes were obtained from the GeneCards and OMIM databases.GO and KEGG pathway enrichment analysis was performed on drug-disease intersection targets using the Metascape database;molecular docking was performed between core target proteins and main active components.A Lewis lung cancer mouse model was established,and intervened with KLJD and cisplatin.Organ indexes and tumor inhibition rate were counted,and Western blot and RT-PCR were used to detect the expressions of key pathway target proteins and mRNA;A549 and H1299 cells were intervened with KLJD,and Western blot was used to detect key target protein expressions.Results Network pharmacology identified 74 active components and 20 key targets of KLJD,primarily involved in biological processes such as cell proliferation and inflammatory response,and pathways in cancer and PI3K/AKT signaling pathway;molecular docking revealed stable binding between EGFR and major compounds.Animal experiments demonstrated that,compared with the model group,the KLJD group showed significantly higher tumor inhibition rate(P<0.01)and downregulation of EGFR,AKT and PI3K protein and mRNA expression in tumor tissues(P<0.05).Compared with the cisplatin group,the combination group exhibited significantly enhanced tumor inhibition rate(P<0.01),elevated thymic and splenic indices(P<0.01),and decreased EGFR,PI3K and AKT protein and mRNA expressions(P<0.01).Cell experiments showed that KLJD concentration-dependently inhibited A549 and H1299 cell proliferation(IC50:14.72 mg/mL and 14.68 mg/mL,respectively).Combined with cisplatin,KLJD synergistically down-regulated EGFR PI3K and AKT protein expressions(P<0.01).Conclusion KLJD effectively enhances cisplatin's chemotherapeutic efficacy in NSCLC by inhibiting the EGFR/PI3K/AKT pathway while improving immune organ function.Its mechanism likely involves multi-target regulation,including suppression of tumor proliferation,promotion of apoptosis,and modulation of the immune microenvironment.

Objective:To analyze the safety and efficacy of multi-vessel minimally invasive cardiac surgery-coronary artery bypass graft(MICS-CABG) through perioperative angiography results and complications.Methods:Clinical data of 1 073 patients who underwent multi-vessel MICS-CABG surgery at Peking University Third Hospital from December 2015 to June 2024 were collected using an ambispective cohort study. Among them, 745 were males(69.4%), with a median age of 65 years(58, 71), and a median ejection fraction of 0.66(0.56, 0.71). Double-vessel or triple-vessel lesions accounted for 932 cases(86.9%), while left main lesions were present in 449 cases(41.8%). The primary outcome was the evaluation of graft patency based on perioperative angiography or coronary artery computed tomography angiography results, while major cardiovascular adverse events during the perioperative period, surgical complications, and other surgical information were secondary outcomes. The clinical efficacy of multi-vessel MICS-CABG was evaluated.Results:In this study, the median number of grafts was 3, and complete revascularization was performed in 1 006 cases(93.8%); total arterial revascularization was performed in 308 cases(28.6%). Perioperative mortality was 11 cases(1.0%), and the main adverse cardiovascular and cerebrovascular events(MACCE) was 50 cases(4.8%). Three cases(0.3%) had poor wound healing, and 79 patients(7.4%) required transfusion. Postoperative coronary angiography was performed in 907 patients(84.5%) and coronary CTA was performed in 52 patients(4.8%), for an overall review rate of 89.4%(959/1073). The overall patency rate of the bridge vessel was 96.9%, and the patency rate of the left internal mammary artery was 98.2%.Conclusion:Multi-vessel MICS-CABG demonstrates excellent perioperative safety and is capable of achieving complete revascularization for the 3 regions of the heart. The quality of the anastomosis and the postoperative patency rate of the grafts is satisfactory.

Objective To determine the effect of isopsoralen(ISO)on the healing of tibia fracture in mice and explore its underlying mechanism.Methods Fifty male C57BL/6 mice(2 month old,20±2 g)were randomly divided into model group and ISO treatment group,with 25 animals in each group.From the 3rd day after modeling,the mice from the ISO group were given an intragastric gavage of 40 mg/kg ISO,once per day for 28 consecutive days,while those of the model group was given same volume of normal saline in same way.On the 7th,14th,21st,and 28th day after gavage,the tibia on the surgical side was taken,and the fracture area was quantified by bone volume/total volume(BV/TV)after micro-CT scanning.The healing and shaping of the fracture end were observed through HE staining.ELISA was used to detect the serum contents of bone alkaline phosphatase(BALP)and procollagen type I N-terminal peptide(PINP)on the 14th day of gavage.Western blotting was employed to determine the expression levels of Collagen Ⅰ,Runx2,BMP2,OSX,and VEGF in the tibial callus tissue in 7 and 14 d after gavage.Vascular perfusion was applied to observe the callus microvessels in 28 d to quantitatively analyze the vascular volume fraction and vessel diameter.Immunohistochemical staining was conducted to observe the expression of VEGF in the callus in 14 d after gavage.Results HE staining displayed that the ISO group had faster healing process than the model group.Micro-CT quantification results showed that the ISO group had higher BV/TV ratio in 7 d after gavage though no statistical difference,significantly higher ratio in 14 d(P＜0.05),but obviously lower ratio in 21 and 28 d after gavage(both P＜0.05)when compared with the model group.The serum contents of BALP and PINP were also remarkably higher in the ISO group than the model group(P＜0.05).Western blotting results indicated that the expression levels of Collagen Ⅰ,Runx2,BMP2,OSX and VEGF in the ISO group were higher than those in the model group(P＜0.05).The results of angiography revealed that the vascular volume fraction and vessel diameter were notably increased in the ISO group than the model group(both P＜0.05).Immunohistochemical assay showed that the expression of VEGF was higher in the ISO group than the model group(P＜0.05).Conclusion ISO can improve the activity of osteoblasts,increase the expression of osteogenesis-related proteins,and accelerate the angiogenesis to promote fracture healing.

This paper aims to focus on and implement strategies for preventing and resolving medical complaints and dis-putes at their emergence.The hospital promptly compiled a summary of the main problems and concerns reported from patients o-ver the past few years.It combined medical practices with the characteristics of admitted patients with severe diseases,complex treatment plans,and high risks.Since 2020,this hospital has been actively engaging with intractable high-risk patients and de-veloped a scheme that engaging clinical departments,medical management,and dispute management departments together to con-duct preoperative/pre-treatment communication.With a focus on patient management,this hospital upholds the concept of the pa-tient-centered humanistic philosophy in the process of doctor-patient communication to enhance the quality of communication.Consequently,the hospital has benefited from the communication scheme,achieving satisfactory effect in ensuring a solid medical safety and reducing the incidence of medical disputes.

ObjectiveTo observe the effect of Feiyanning prescription （FYN） on cisplatin （DDP） resistance in non-small cell lung cancer （NSCLC） and explore the underlying mechanism. MethodCell counting kit-8 （CCK-8） assay was used to detect the proliferation of A549 and A549/DDP （DDP-resistant） cells treated by DDP （0， 2.0， 4.0， 6.0， 8.0， 10.0 mg⋅L^-1） and the proliferation of A549/DDP cells treated by FYN （0， 100， 200， 300， 400， 500， 600 mg⋅L^-1）. Based on immunofluorescence staining and Western blot （WB）， the expression of epithelial mesenchymal transition （EMT）-related proteins in A549 and A549/DDP groups was observed. A549/DDP cells were classified into control group， FYN group （200 mg⋅L^-1）， DDP group （6.0 mg⋅L^-1）， and combination group ［FYN （200 mg⋅L^-1） + DDP （6.0 mg⋅L^-1）］ and respectively treated with corresponding drugs. Then， invasion ability of each group was examined by transwell assay， and the expression of EMT-related proteins in each group by WB. Moreover， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） and immunofluorescence staining were separately applied to detect the mRNA and protein expression of drug resistance-related factors in each group， respectively. ResultCompared with A549 group， A549/DDP group showed high resistance to DDP （P<0.01）， low expression of E-cadherin， and high protein expression of Vimentin， N-cadherin， and Snail （P<0.05， P<0.01）. As compared with the control group， FYN inhibited the proliferation of A549/DDP cells in a concentration-dependent manner （P<0.01）， and the FYN group， DDP group， and combination group demonstrated low invasion ability （P<0.01）. In addition， the invasion ability in the combination group was particularly lower than that in the DDP group （P<0.01）. The expression of E-cadherin protein was higher and the protein expression of N-cadherin， Vimentin， and Snail was lower in the in FYN group than in the control group （P<0.01）. The protein expression of E-cadherin， N-cadherin， and Vimentin was lower and the expression of Snail was higher in the DDP group than in the control group （P<0.05，P<0.01）. The protein expression of E-cadherin， N-cadherin， Vimentin， and Snail in the combination group decreased as compared with that in the control group （P<0.01）. Compared with the DDP alone， the combination raised the expression of E-cadherin and lowered the protein expression of N-cadherin， Vimentin， and Snail （P<0.01）. The protein and mRNA expression of lung resistance-related protein （LRP） and multidrug resistance 1 （MDR1） was lower and the protein and mRNA expression of topoisomerase Ⅱα （TOPO Ⅱα） was higher in the FYN group than in the control group （P<0.01）. The protein and mRNA expression of LRP， MDR1， and TOPO Ⅱα was higher in the DDP group than in the control group （P<0.01）. The expression of LRP protein and mRNA showed no significant variation， but the protein and mRNA expression of MDR1 and TOPO Ⅱα increased in the combination group compared with those in the control group （P<0.01）. Compared with the DDP group， FYN group and combination group showed low protein and mRNA expression of LRP and MDR1 and high protein and mRNA expression of TOPO Ⅱα （P<0.01）. Compared with FYN， the combination elevated the protein and mRNA expression of LRP， MDR1， and TOPO Ⅱα （P<0.01）. ConclusionFYN prescription can reverse the DDP resistance of NSCLC by modulating EMT.

BACKGROUND: Management of gastric leak after sleeve gastrectomy (SG) is challenging due to its unpredictable outcomes. We aimed to summarize the characteristics of SG leaks and analyze interventions and corresponding outcomes in a real-world setting. METHODS: To retrospectively review of 15,721 SG procedures from 2010 to 2020 based on a national registry. A cumulative sum analysis was used to identify a fitting curve of gastric leak rate. The Kaplan-Meier method and log-rank tests were performed to calculate and compare the probabilities of relevant outcomes. The logistic regression analysis was conducted to determine the predictors of acute leaks. RESULTS: A total of 78 cases of SG leaks were collected with an incidence of 0.5% (78/15,721) from this registry (6 patients who had the primary SG in non-participating centers). After accumulating 260 cases in a bariatric surgery center, the leak rate decreased to a stably low value of under 1.17%. The significant differences presented in sex, waist circumference, and the proportion of hypoproteinemia and type 2 diabetes at baseline between patients with SG leak and the whole registry population ( P = 0.005, = 0.026, <0.001, and = 0.001, respectively). Moreover, 83.1% (59/71) of the leakage was near the esophagogastric junction region. Leakage healed in 64 (88.9%, 64/72) patients. The median healing time of acute and non-acute leaks was 5.93 months and 8.12 months, respectively. Acute leak (38/72, 52.8%) was the predominant type with a cumulative reoperation rate >50%, whereas the cumulative healing probability in the patients who required surgical treatment was significantly lower than those requring non-surgical treatment ( P = 0.013). Precise dissection in the His angle area was independently associated with a lower acute leak rate, whereas preservation ≥2 cm distance from the His angle area was an independent risk factor. CONCLUSIONS Male sex, elevated waist circumference, hypoproteinaemia, and type 2 diabetes are risk factors of gastric leaks after SG. Optimizing surgical techniques, including precise dissection of His angle area and preservation of smaller gastric fundus, should be suggested to prevent acute leaks.
Humans ; Male ; Retrospective Studies ; Diabetes Mellitus, Type 2/complications* ; Obesity, Morbid ; Anastomotic Leak/epidemiology* ; Gastrectomy/methods* ; Reoperation/methods* ; Registries ; Laparoscopy/methods* ; Treatment Outcome