ObjectiveWith the epidermal growth factor receptor（EGFR）/Signal Transducers and Activators of Transcription（STAT3）/Hexokinase 2（HK2） signaling pathway in atherosclerosis （AS） and ovarian cancer （OC） as the entry point， this paper discusses the molecular mechanism of Gypenoside L （Gyp-L） treating AS and OC with different diseases， provides a new perspective and theoretical basis for TCM treating AS and OC with EGFR-STAT3-HK2 pathway， and enriches the scientific connotation of the theory of "cytoskeleton in the heart". MethodsCCK-8 was used to detect the proliferation of HUVEC and OVCAR-3 cells， in order to determine the intervention concentration for subsequent experiments. The colorimetric method was used to detect the NO content in HUVEC and the contents of pyruvate and LDH in two cell lines. Cell cloning experiments and scratch experiments reflect the proliferation and migration ability of OVCAR-3 cells. Western blot was used to detect the expression levels of relevant proteins. Furthermore， two cell models overexpressing EGFR were constructed and co treated with Gyp-L. HUVEC cells were divided into control， ox-LDL， OE-NC， OE-EGFR， OE-NC+Gyp-L， and OE-EGFR+Gyp-L group. OVCAR-3 cells were divided into control， OE-NC， OE-EGFR ， OE-NC+Gyp-L， and OE-EGFR+Gyp-L group. The colorimetric method was used to detect the NO content in HUVEC and the contents of pyruvate and LDH in two cell lines. Western blot was used to detect the expression levels of EGFR-STAT3-HK2 pathway related proteins. Cell cloning experiments and scratch experiments reflect the proliferation and migration ability of OVCAR-3 cells. ResultsGyp-L can significantly reduce the NO content of HUVEC and the pyruvate and LDH content of two cell lines （P<0.05）； Inhibit the proliferation and migration ability of OVCAR-3 cells； Reduce the expression levels of EGFR/STAT3/HK2 pathway related proteins in HUVEC and OVCAR-3 cell lines （P<0.05）， and inhibit the glycolysis pathway. ConclusionGyp-L can inhibit glycolysis in HUVEC and OVCAR-3 cells through the EGFR/STAT3/HK2 pathway，thereby suppressing the occurrence and development of AS and OC.

ObjectiveWith the epidermal growth factor receptor（EGFR）/Signal Transducers and Activators of Transcription（STAT3）/Hexokinase 2（HK2） signaling pathway in atherosclerosis （AS） and ovarian cancer （OC） as the entry point， this paper discusses the molecular mechanism of Gypenoside L （Gyp-L） treating AS and OC with different diseases， provides a new perspective and theoretical basis for TCM treating AS and OC with EGFR-STAT3-HK2 pathway， and enriches the scientific connotation of the theory of "cytoskeleton in the heart". MethodsCCK-8 was used to detect the proliferation of HUVEC and OVCAR-3 cells， in order to determine the intervention concentration for subsequent experiments. The colorimetric method was used to detect the NO content in HUVEC and the contents of pyruvate and LDH in two cell lines. Cell cloning experiments and scratch experiments reflect the proliferation and migration ability of OVCAR-3 cells. Western blot was used to detect the expression levels of relevant proteins. Furthermore， two cell models overexpressing EGFR were constructed and co treated with Gyp-L. HUVEC cells were divided into control， ox-LDL， OE-NC， OE-EGFR， OE-NC+Gyp-L， and OE-EGFR+Gyp-L group. OVCAR-3 cells were divided into control， OE-NC， OE-EGFR ， OE-NC+Gyp-L， and OE-EGFR+Gyp-L group. The colorimetric method was used to detect the NO content in HUVEC and the contents of pyruvate and LDH in two cell lines. Western blot was used to detect the expression levels of EGFR-STAT3-HK2 pathway related proteins. Cell cloning experiments and scratch experiments reflect the proliferation and migration ability of OVCAR-3 cells. ResultsGyp-L can significantly reduce the NO content of HUVEC and the pyruvate and LDH content of two cell lines （P<0.05）； Inhibit the proliferation and migration ability of OVCAR-3 cells； Reduce the expression levels of EGFR/STAT3/HK2 pathway related proteins in HUVEC and OVCAR-3 cell lines （P<0.05）， and inhibit the glycolysis pathway. ConclusionGyp-L can inhibit glycolysis in HUVEC and OVCAR-3 cells through the EGFR/STAT3/HK2 pathway，thereby suppressing the occurrence and development of AS and OC.

ObjectiveTo explore the effect of gypenosides （GPs） on liver lipid deposition in metabolism-associated fatty liver disease （MAFLD） mice and its mechanism based on classical/non-classical ferroptosis. MethodsEight male C57BL/6 mice in a blank group and 32 male apolipoprotein E gene knockout （ApoE^-/-） mice were randomly divided into a model group， a low-dose GPs （GPs-L） group， a high-dose GPs （GPs-H） group， and a simvastatin （SV） group. Starting from the second week， mice in the blank group were given a maintenance diet， and the other four groups were fed a high-fat diet daily. After eight weeks of feeding， mice in the GPs-L and GPs-H groups were given GPs of 1.487 mg·kg^-1·d^-1 and 2.973 mg·kg^-1·d^-1， respectively， and mice in the SV group were given simvastatin of 2.275 mg·kg^-1·d^-1. Mice in the blank group and the model group were given saline of equal volume by gavage for four weeks. The content of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in the serum of mice in each group was detected by an automatic biochemical analyzer. The level of non-esterified fatty acid （NEFA） and TG in the mouse liver was measured by the kit. The change in liver tissue structure and lipid deposition was observed by hematoxylin-eosin （HE） and oil red O staining. The levels of coenzyme Q₁₀ （CoQ₁₀）， glutathione （GSH）， malondialdehyde （MDA）， and Fe²⁺ in serum， as well as nicotinamide adenine dinucleotide phosphate ［NAD（P）H］ in the liver were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of ferroptosis suppressor protein 1 （FSP1） in the liver of mice was observed by the immunohistochemical （IHC） method， and the expression of genes and proteins related to classical and non-classical ferroptosis pathways was analyzed by real-time polymerase chain reaction （Real-time PCR） and Wes automated protein expression analysis system. ResultsCompared with those in the blank group， the levels of TC， TG， LDL-C， ALT， and AST in serum and TG and NEFA in the liver in the model group were significantly increased， and the level of HDL-C in serum was significantly decreased （P<0.01）. The liver tissue structure changed， and there were fat vacuoles of different sizes and a large number of red lipid droplets， with obvious lipid deposition. The level of CoQ10 and GSH in serum and NADH in the liver were significantly decreased， while the level of MDA and Fe²⁺ in serum was significantly increased （P<0.01）. The mRNA and protein expressions of cystine/glutamate transporter （xCT/SLC7A11）， glutathione peroxidase （GPX4）， p62， nuclear factor E₂-related factor 2 （Nrf2）， and FSP1 were significantly decreased， and the mRNA and protein expressions of tumor antigen （p53）， spermidine/spermine N1-acetyltransferase 1 （SAT1）， arachidonate 15-lipoxygenase （ALOX15）， and Kelch-like epichlorohydrin-associated protein-1 （Keap1） were significantly increased （P<0.01）. Compared with those in the model group， the level of TC， TG， LDL-C， ALT， and AST in serum and TG and NEFA in the liver of mice in the GPs-L， GPs-H， and SV groups were decreased， while the level of HDL-C in serum was significantly increased （P<0.05， P<0.01）. The liver tissue structure and lipid deposition were improved. The levels of CoQ10 and GSH in serum and NADH in the liver were significantly increased， while the levels of MDA and Fe²⁺ in serum were significantly decreased （P<0.05， P<0.01）. The mRNA and protein expressions of xCT， GPX4， p62， Nrf2， and FSP1 were significantly increased， while the mRNA and protein expressions of p53， SAT1， ALOX15， and Keap1 were significantly decreased （P<0.05， P<0.01）. ConclusionGPs can interfere with liver lipid deposition in MAFLD mice through classical/non-classical ferroptosis pathways.

ObjectiveTo explore the effect of gypenosides （GPs） on liver lipid deposition in metabolism-associated fatty liver disease （MAFLD） mice and its mechanism based on classical/non-classical ferroptosis. MethodsEight male C57BL/6 mice in a blank group and 32 male apolipoprotein E gene knockout （ApoE^-/-） mice were randomly divided into a model group， a low-dose GPs （GPs-L） group， a high-dose GPs （GPs-H） group， and a simvastatin （SV） group. Starting from the second week， mice in the blank group were given a maintenance diet， and the other four groups were fed a high-fat diet daily. After eight weeks of feeding， mice in the GPs-L and GPs-H groups were given GPs of 1.487 mg·kg^-1·d^-1 and 2.973 mg·kg^-1·d^-1， respectively， and mice in the SV group were given simvastatin of 2.275 mg·kg^-1·d^-1. Mice in the blank group and the model group were given saline of equal volume by gavage for four weeks. The content of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in the serum of mice in each group was detected by an automatic biochemical analyzer. The level of non-esterified fatty acid （NEFA） and TG in the mouse liver was measured by the kit. The change in liver tissue structure and lipid deposition was observed by hematoxylin-eosin （HE） and oil red O staining. The levels of coenzyme Q₁₀ （CoQ₁₀）， glutathione （GSH）， malondialdehyde （MDA）， and Fe²⁺ in serum， as well as nicotinamide adenine dinucleotide phosphate ［NAD（P）H］ in the liver were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of ferroptosis suppressor protein 1 （FSP1） in the liver of mice was observed by the immunohistochemical （IHC） method， and the expression of genes and proteins related to classical and non-classical ferroptosis pathways was analyzed by real-time polymerase chain reaction （Real-time PCR） and Wes automated protein expression analysis system. ResultsCompared with those in the blank group， the levels of TC， TG， LDL-C， ALT， and AST in serum and TG and NEFA in the liver in the model group were significantly increased， and the level of HDL-C in serum was significantly decreased （P<0.01）. The liver tissue structure changed， and there were fat vacuoles of different sizes and a large number of red lipid droplets， with obvious lipid deposition. The level of CoQ10 and GSH in serum and NADH in the liver were significantly decreased， while the level of MDA and Fe²⁺ in serum was significantly increased （P<0.01）. The mRNA and protein expressions of cystine/glutamate transporter （xCT/SLC7A11）， glutathione peroxidase （GPX4）， p62， nuclear factor E₂-related factor 2 （Nrf2）， and FSP1 were significantly decreased， and the mRNA and protein expressions of tumor antigen （p53）， spermidine/spermine N1-acetyltransferase 1 （SAT1）， arachidonate 15-lipoxygenase （ALOX15）， and Kelch-like epichlorohydrin-associated protein-1 （Keap1） were significantly increased （P<0.01）. Compared with those in the model group， the level of TC， TG， LDL-C， ALT， and AST in serum and TG and NEFA in the liver of mice in the GPs-L， GPs-H， and SV groups were decreased， while the level of HDL-C in serum was significantly increased （P<0.05， P<0.01）. The liver tissue structure and lipid deposition were improved. The levels of CoQ10 and GSH in serum and NADH in the liver were significantly increased， while the levels of MDA and Fe²⁺ in serum were significantly decreased （P<0.05， P<0.01）. The mRNA and protein expressions of xCT， GPX4， p62， Nrf2， and FSP1 were significantly increased， while the mRNA and protein expressions of p53， SAT1， ALOX15， and Keap1 were significantly decreased （P<0.05， P<0.01）. ConclusionGPs can interfere with liver lipid deposition in MAFLD mice through classical/non-classical ferroptosis pathways.

There is an urgent need for innovative graduate students in clinical medicine who possess the ability to apply interdisciplinary knowledge to address complex and cutting-edge challenges in the background of new medical science. The two training modes, "X + Medicine" and "Medicine + X", are essential measures to promote the construction of new medical science. The "X + Medicine" mode is better suited for cultivating the exceptional medical talents; however, it has limitations such as constrained applicability and talent attrition. The "Medicine + X" mode can be applied in various ways in general medical schools, but it has not broken through the boundaries of traditional disciplines or achieved a substantial scale. In order to provide useful insights for cultivating innovative graduate students in clinical medicine who meet the needs of new medical science, we propose the integration of curriculums, the implementation of quantitative evaluation, and the increase in funding for scientific research to make the "X + Medicine" more adaptable to China's national conditions and to mitigate talent loss. Additionally, we suggest strengthening overall management and expanding collaboration with other schools and companies to improve the "Medicine + X" mode.

Improving the sense of belonging of the elderly in nursing institutions is of great significance to enhance their sense of self-worth and self-identity,and further meet the spiritual needs of the elderly in nursing institutions.This paper reviewed the concept,current situation,evaluation tools and influencing factors of the elderly's sense of belonging in nursing institutions,and proposes that there is a lack of tools to measure the sense of belonging of the elderly in nursing institutions,and the intervention strategies with caregivers as the core needs to be further explored.

The pachychoroid spectrum disorders (PSD) refers to a group of clinical disorders characterized by common features of pathological choroidal thickening and potential pathogenic mechanisms. The pathological mechanism of PSD is very complex, and the theory of venous overload provides valuable research directions. The multimodal imaging technology represented by optical coherence tomography angiography has continuously evolved to provide clear and three-dimensional images of the fundus, making it easier to diagnose and monitor PSD at an early stage. There is no unified consensus on how to develop a treatment plan for PSD, and current research has shown that feasible treatments include drug therapy, laser photocoagulation therapy, and photodynamic therapy. However, the evidence of effectiveness and safety provided by these studies is still not sufficient. Surgery and integrative Chinese and Western medicine may provide new prospects for the treatment of PSD. In the future, it is necessary to further develop reasonable research programs, expand the sample size, strengthen follow-up observation, and provide more safe and effective treatment programs for patients.

Objective:To further investigate the safety and efficacy of Belimumab in the treatment of patients with systemic lupus erythematosus (SLE).Methods:All SLE patients treated with Belimumab from May 1, 2020 to February 1, 2022 in Peking Union Medical College Hospital were retrospectively collected and analyzed. The clinical manifestations, the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2000) score, and laboratory test such as levels of anti-dsDNA antibody, the medication before and after Belimumab treatment, adverse events were collected. Normally distributed data were tested using the t-test, otherwise the Wilcoxon paired signed rank test was used. Results:A total of 81 patients were enrolled in this study. The use of belimumab could significantly decrease the SLEDAI-2000 score [10.00(7.75, 12.00) vs. 4.00(3.75, 6.00), Z=-5.38, P<0.001], ESR of SLE patients [19.50(12.75, 32.25) mm/1 h vs. 14.00(7.75, 20.25) mm/1 h, Z=-3.71, P=0.003], anti-dsDNA titer detected by CLIFT [300.00 (117.00, 864.00) vs. 183.00(100.00, 471.00), Z=-4.15, P=0.001], meanwhile, increase the complement C3 [0.78 (0.62, 0.97)g/L vs. 0.69 (0.55, 0.84)g/L, Z=-4.68, P<0.001], and the complement C4 [0.12 (0.08, 0.19)g/L vs. 0.10 (0.05, 0.14)g/L, Z=-4.78, P<0.001]. We also observed that with the use of Belimumab, the dosage of Glucocorticoids decreased significantly, which were [10.00(7.50, 22.50) mg vs. 7.50(5.00, 10.00) mg, Z=-4.90, P<0.001]. In addition, the antibody of IgG, IgA and IgM decreased significantly. Only one patient stopped the administration of Belimumab due to the low level of immunoglobulin. Conclusion:Belimumab can alleviate disease activity of patients with SLE and help in safely tapering the daily dose of glucocorticoid with good safety.

ObjectiveTo investigate the clinicopathological features， diagnosis and treatment methods， and prognosis of gallbladder sarcomatoid carcinoma （GBSC）. MethodsA retrospective analysis was performed for the clinical data of 16 patients with GBSC who were admitted to The First Affiliated Hospital of Zhengzhou University from January 2015 to April 2023， including general information， clinical manifestations， imaging features， pathological features， and treatment modality， and follow-up was performed for all patients. The Kaplan-Meier method was used to perform the survival analysis and plot the survival curve， and the Log-rank test was used for comparison between groups. ResultsAmong the 16 patients， there were 6 male patients and 10 female patients， with a mean age of 62.9±8.4 years. The main clinical manifestations were right upper abdominal pain in 13 patients （81.3%）， nausea in 5 patients （31.3%）， abdominal distension in 4 patients （25.0%）， poor appetite in 3 patients （18.8%）， weakness in 2 patients （12.5%）， fever in 2 patients （12.5%）， and jaundice in 1 patient （6.3%）， and 3 patients were asymptomatic and were found to have this disease by physical examination. Of all patients， 81.3% （13/16） were in the advanced stage （stage Ⅲ/Ⅳ） at the time of initial diagnosis. Histopathological examination showed that some cancer cells were spindle-shaped under the microscope， with marked nuclear division and noticeable heteromorphism. Immunohistochemistry showed a positive expression rate of 100% （16/16） for Vimentin， AE1/AE3， and CK8/18， and Ki-67 proliferation index was highly expressed in 81.3% （13/16） of the patients （≥50%）， with a median of 70% （range 20%‍ ‍—‍ ‍90%）. All 16 patients underwent surgical treatment， with radical surgery in 11 patients and palliative surgery in 5 patients， among whom 9 received R0 resection， 2 received R1 resection， and 5 received R2 resection， and 7 patients received adjuvant therapy after surgery. Effective follow-up was achieved for all 16 patients， with a follow-up time of 0.5‍ ‍—‍ ‍26.0 months and a median follow-up time of 11.0 months. By the end of follow-up， 2 patients survived and 14 patients died due to tumor recurrence or metastasis， with a median survival time of 10.0 months， and the 1- and 2-year cumulative survival rates after surgery were 31.3% and 8.3%， respectively. The prognostic analysis showed that TNM stage （χ²=6.727， P=0.009）， surgical approach （χ²=7.508， P=0.006）， margin condition （χ²=7.934， P=0.005）， and adjuvant therapy （χ²=4.608， P=0.032） were associated with the prognosis of patients. ConclusionThe clinical manifestations of GBSC lack specificity， and a confirmed diagnosis relies on immunohistochemical analysis. Most patients are in the advanced disease at the time of initial diagnosis and tend to have a poor prognosis. There are currently no targeted therapies for this disease， and radical surgery with negative margins and adjuvant therapy can improve the survival rate of patients.

OBJECTIVE To study the effects of methimazole on the urinary metabolomics of hyperthyroidism rats， and to preliminarily investigate its possible mechanism. METHODS Thirty SD rats were randomly divided into control group， model group and methimazole group， with 10 rats in each group. Except for the control group， the rats in the other two groups were given Levothyroxine sodium tablets 160 mg/kg by intragastric administration for 15 days； at the same time， methimazole group was additionally given methimazole 3.6 mg/kg daily by intragastric administration every day. The basic condition of the rats was observed， and the body weight and anal temperature were measured. After the last medication， the serum levels of triiodothyronine （T3）， tetraiodothyronine （T4）， free triiodothyronine （FT3）， free tetraiodothyronine （FT4）， and thyroid stimulating hormone （TSH） were determined； 24-hour urine was collected on the 15th day after administration. UPLC-TOF-MS was used to analyze the urine metabolomics of rats. Principal component analysis and orthogonal partial least squares-discriminant analysis were used to screen out related differential metabolites， and potential metabolic pathways were analyzed by using HMDB and KEGG. RESULTS Compared with the control group， the rectal temperature， serum levels of T3， T4， FT3 and FT4， the expressions of differential metabolites sebacic acid， cholic acid 3-O-glucuronic acid and N6， N6， N6-trimethyl-L-lysine in urine were significantly up-regulated， while body weight， serum level of TSH， the expressions of deoxycytidine and 2-oxo-4-methylthiobutanoic acid in urine were significantly down-regulated （P＜0.01）. Compared with model group， above indexes of rats were reversed significantly in methimazole group （P＜0.01 or P＜0.05）. Above five differential metabolites were mainly involved in four signaling pathways: pentose and glucuronate interaction， lysine degradation， cysteine and methionine metabolism， and pyrimidine metabolism. CONCLUSIONS Methimazole might improve hyperthyroidism by modulating the four pathways of pentose and glucuronate interaction， lysine degradation， cysteine and methionine metabolism， and pyrimidine metabolism.