This review systematically summarizes the unique metabolic mechanisms of breast cancer,their interac-tions with the tumor microenvironment(TME),and the latest advances in targeted therapies.The interplay between metabolic reprogramming and the TME underpins malignant progression and therapeutic resistance.Breast cancer cells reshape energy supply through the Warburg effect,aberrant fatty acid synthesis,and amino acid metabolism,while immune cells,fibroblasts,and the acidic milieu within the TME promote immune evasion and drug resistance via metabolic coupling.Although traditional strategies targeting key metabolic enzymes remain valuable,they are often insufficient to overcome metabolic adaptability.In recent years,combined metabolic and immunotherapeutic approaches have emerged as promising strategies:by reducing lactate accumulation,restoring T-cell function,and reprogramming tumor-associated macrophages and cancer-associated fibroblasts,these therapies can remodel the immunosuppressive microenvironment and enhance immunotherapy efficacy.The application of metabolomics and single-cell sequencing further elucidates breast cancer heterogeneity,providing a basis for individualized precision treatment.Future challenges include deciphering resistance mechanisms,developing highly selective metabolic in-hibitors,and designing integrated multi-omics-based therapeutic regimens.

Objective:To establish the normal reference value of left ventricular function parameters by cadmium-zinc-tellurium (CZT) SPECT stress gated myocardial perfusion imaging (G-MPI) in low-likelihood of stable coronary artery disease (SCAD).Methods:From March 2022 to August 2022, 348 consecutive SCAD patients (146 males, 202 females, age (58±10) years) who underwent exercise or pharmacological stress G-MPI (CZT SPECT) in Beijing Anzhen Hospital, Capital Medical University were retrospectively recruited. Left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), and left ventricular ejection fraction (LVEF) were acquired using quantitative gated SPECT (QGS) analysis. EDV and ESV were corrected by body surface area (BSA) to obtain EDV index (EDVI) and ESV index (ESVI), respectively. Independent-sample t test, one-way analysis of variance and Mann-Whitney U test were used for data analysis. The influences of EDV, ESV, EDVI, ESVI and LVEF were analyzed by multiple regressions for linear models. Results:There were 314 patients with low-likelihood of SCAD (128 males, 186 females, age (58±10) years) and 34 normal controls (18 males, 16 females, age (55±10) years). There were no significant differences of basic clinical characteristics and left ventricular function parameters in different genders between 2 groups ( z values: from -1.74 to -0.02, t values: from -1.16 to 1.17, all P>0.05). Using the 95% CI as the cut-off value for left ventricular function parameters in patients with a low-likelihood of SCAD, the upper limits of EDV, ESV, EDVI and ESVI in females and males were 84 and 111 ml, 30 and 44 ml, 47 and 54 ml/m 2, 17 and 21 ml/m 2, respectively, and the lower limit of LVEF in females and males were 58% and 55%, respectively. In the low-likelihood of SCAD group, the EDV ((58±13) vs (77±17) ml) and ESV ((16±7) vs (26±9) ml) of females were smaller than those of males ( t values: 10.65, 10.35, both P<0.001), while LVEF of females was higher than that of males ((72±7)% vs (67±6)%; t=-6.23, P<0.001). However, there were no significant differences in left ventricular function parameters among different age groups with the same gender ( F values: 0.12-2.19, all P>0.05). Based on multiple regression for linear models, the primary predictors of EDV, ESV and LVEF were gender and weight ( β values: from -0.380 to 0.358, all P<0.05). Conclusions:Normal reference values of left ventricular function parameters are established by CZT SPECT stress G-MPI in low-likelihood of SCAD patients. Left ventricular EDV and ESV of females are smaller than those of males, while LVEF of females is higher than that of males. The influence of gender on left ventricular function parameters should be considered in clinical practice.

OBJECTIVE：To analyze the metabolites of tetrahydroxystilbene glucoside （THSG）and speculate its metabolism pathway in rats. METHODS ：Male SD rats were randomly divided into plasma group （n＝3），urine group （n＝3），bile group （n＝3），and tissue group （n＝9）. Each group was given single dose of THSG 200 mg/kg intragastrically. Plasma samples 10，30 min and 1，1.5，2，4 h after medication ，the unrine 0-6 h after medication ，the bile 0-4 h after medication ，the tissue of heart ， liver，spleen，lung，kidney and stomach 30 min and 1，2 h after medication （3 at each time point ）were collected respectively.After precipitated with methanol ，the metabolites of samples were analyzed and identified by UHPLC-Q-Exactive Orbitrap MS and mass loss filtration （MDF）. Its metabolism pathway was speculated. RESULTS：In the blood ，urine，bile，heart，liver，spleen， lung，kidney，stomach samples ，6，7，11，1，5，1，3，4，4 metabolites were detected ，including two phase Ⅰ（hydrolysis， hydrogenation and hydroxylation ）metabolites，18 phase Ⅱ（glucuronic acid binding and sulfation ）metabolites. There were 12 glucuronic acid binding products. CONCLUSIONS：Most of the metabolites of THSG are found in bile ，mainly glucuronic acid binding products of phase Ⅱ metabolite THSG ； main metabolic pathways involve glucose hydrolysis ， hydrogenation， hydroxylation，glucuronic acid binding and sulfation.

ObjectiveTo investigate the tolerance, pharmacokinetics, and antiviral activity of coblopasvir hydrochloride capsules in patients with hepatitis C. MethodsA total of 36 patients with hepatitis C who were admitted to The First Hospital of Jilin University from November 2016 to January 2017 were enrolled as subjects, and four dose groups (30 mg, 60 mg, 90 mg, and 120 mg) and one placebo group were established. The subjects were administered once daily for 3 consecutive days; tolerance was evaluated on D2 and D6, and follow-up was performed on D8 and D10. The subjects were enrolled based on single dose escalation, and a multiple-dose study was conducted under the premise of good tolerance to single dose. Liquid chromatography-tandem mass spectrometry was used to measure the plasma concentration of coblopasvir hydrochloride in human body, and WinNonlin 6.4 software was used to calculate main pharmacokinetic parameters. HCV RNA load was used to evaluate antiviral activity at different time points; a one-way analysis of variance was used for comparison between multiple groups, and the LSD t-test was used for further comparison between two groups. ResultsAfter coblopasvir hydrochloride capsules were administered orally once a day at a dose of 30-120 mg, the plasma concentration and exposure of coblopasvir hydrochloride increased with the increase in dose. There were no significant differences in plasma concentration and exposure between multiple-dose administration and single-dose administration in a fasting state, without accumulation in human body. After the oral administration of coblopasvir hydrochloride capsules once a day, the subjects with HCV genotype 1b had a reduction in HCV RNA load since baseline, with the lowest level at 120 hours, and there was a significant difference in antiviral activity between different dose groups (F=14.621, P＜0.000 1), among which the 60 mg group had a significantly greater reduction than the 30 mg group (P=0.025), while there was no significant difference between the 60 mg group and the 90/120 mg group (P＞0.05). There was no significant difference in HCV RNA load between different groups of patients with HCV genotype 2a (P＞0.05). Of all 36 subjects, 20 reported 34 cases of treatment-emergent adverse events, among which 19 cases were associated with coblopasvir hydrochloride, and no significant adverse events or serious adverse events were observed. ConclusionOral administration of coblopasvir hydrochloride capsules in a fasting state at a dose of 30-120 mg/d (for 3 consecutive days) has good safety and antiviral activity. Therefore, it has good application prospect in the treatment of HCV infection and provides a basis for dose selection in phrase 2 study.

SIGIRR, a member of the interleukin 1 receptor superfamily, is also known as a single immunoglobulin (Ig)-related receptor, which is believed to play a key role in the development of inflammation and the regulation of anti-inflammatory effects. Some studies believe that the abnormal down-regulation of SIGIRR can lead to intestinal inflammation, pyelonephritis, systemic lupus erythematosus and other diseases, but it can promote tumor growth and potentially cause anti-tumor immune damage when its genes are overexpressed. Therefore, the role of SIGIRR in disease occurrence and development is considered a double-edged sword. At present, the detailed molecular mechanism of SIGIRR′s biological role is not fully understood. This article reviews the functions of SIGIRR in the occurrence and development of immune-related diseases and immune regulation, as well as related cell signaling pathways, which have been discovered and confirmed.

OBJECTIVE：To establ ish the fingerprint of Sojae Semen Nigrum and content determination method of 5 kinds of isoflavones，so as to provide reference for controlling its quality better. METHODS ：HPLC method was adopted to establish the fingerprint and detect the contents of 5 kinds of isoflavones. The determination was performed on Phenomenex C 18 column with mobile phase consisted of acetonitrile- 0.12％ formic acid solution （gradient elution ）at the flow rate of 1 mL/min. The detection wavelength was set at 260 nm；the column temperature was 30 ℃ and sample size was 10 μL. Using daidzin as reference，HPLC fingerprints of 12 batches of samples were determined. The similarity of 12 batches of samples was evaluated by TCM Chromatographic Fingerprint Similarity Evaluation System （2012A） to confirm common peak. Cluster analysis and principal component analysis were performed by using SPSS 20.0 software and SIMCA 13.0 software. RESULTS ：There were 19 common peaks in HPLC fingerprints of 12 batches of samples ，the similarity of which was higher than 0.94. Totally 5 components were identified，such as daidzin ，glycitin，genistin，daidzein，genistein. Cluster analysis showed that 12 batches of Sojae Semen Nigrum were clustered into 2 categories，i.e. S 1-S3 clustered into one category ，and S 4-S12 clustered into the other category. By principal component analysis ，the contribution rates of two principle components were 53.261％ and 40.715％；accumulative contribution rate was 93.976％. The linear range of above 5 components were 5.97-191.00 µg/mL（r＝0.999 9），1.05-33.46 µg/mL（r＝0.999 9）， 8.93-285.61 µg/mL（r＝0.999 5），0.82-26.33 µg/mL（r＝0.999 9），0.93-29.64 µg/mL（r＝0.999 7），respectively. The limits of quantitation were 0.881 1，0.611 6，0.078 6，0.243 3，0.511 6 μg/mL，respectively. The limits of detection were 0.264 3，0.244 7， 0.021 4，0.124 8，0.106 7 μg/mL，respectively. RSDs of precision ，stability，reproducibility and durability tests were all lower than 5％. Recoveries were 95.15％-96.56％（RSD＝0.51％，n＝6），98.52％-103.45％（RSD＝1.88％，n＝6），95.37％-97.91％ （RSD＝0.95％，n＝6），99.75％-102.00％（RSD＝0.78％，n＝6），100.26％-103.65％（RSD＝1.21％，n＝6）. Among 12 batches of Sojae Semen Nigrum ，the contents of above 5 components were 0.178 3-0.265 9，0.021 7-0.096 2，0.288 5-0.597 2，0.014 1- 0.058 8，0.012 9-0.082 9 mg/g. CONCLUSIONS ：Established HPLC fingerprint and content determination method of 5 kinds of isoflavones can be used for quality control of Sojea Semen Nigrum. The Isoflavone components are similar ，but the contents are different among Sojae Semen Nigrum from different producing areas.

In general, the application conditions of linear regression models could be met after the natural logarithmic transformation of data. From the practical perspective, this paper introduced the linear regression models with natural logarithmic transformation of independent variable, dependent variable, and both independent and dependent variables in detail. The paper illustrated why the equation and coefficients could not be directly explained after the natural logarithmic transformation of data. The percentage changes of X and/or Y were applied to elaborate the principle and method for the explanation of the equation and coefficients. Three examples were used to fit simple linear models with natural logarithmic transformation of independent, dependent, and both independent and dependent variables and the results of theses models were explained in detail.

In general, the application conditions of linear regression models could be met after the natural logarithmic transformation of data. From the practical perspective, this paper introduced the linear regression models with natural logarithmic transformation of independent variable, dependent variable, and both independent and dependent variables in detail. The paper illustrated why the equation and coefficients could not be directly explained after the natural logarithmic transformation of data. The percentage changes of X and/or Y were applied to elaborate the principle and method for the explanation of the equation and coefficients. Three examples were used to fit simple linear models with natural logarithmic transformation of independent, dependent, and both independent and dependent variables and the results of theses models were explained in detail.

Presently, nonalcoholic fatty liver disease has become the most common pathogenic factor of chronic liver disease worldwide that can lead to the occurrence of hepatocellular carcinoma (HCC). Lipid metabolism in cancer cells is closely related to tumorgenesis, invasion and metastasis, and thus acts as one of the hallmark of cancer cells. Lipolipomics is an important branch of metabolomics, which has been adapted recently in the study of HCC for analysis of the structure and function of lipid components by chromatography and mass spectrometry. Fatty acids, glycerides, glycerophospholipids, sphingolipids, and sterol are significantly different in HCC tissues or serum. Therefore, it contributes to the diagnosis, determination of prognosis, mechanistic study and targeted therapy of HCC.

Objective:To analyze the safety of generics and lactation of commonly used drugs in outpatient and emergency department of a children's hospital in Shanghai to formulate the related high-risk medicines list. Methods:According to the drug directory for outpatient and emergency department in the sample hospital,the medication assistant software was used to check the safety level of the related drugs used during pregnancy and lactation. Drugs with pregnancy safety grade D or X,and the lactation safety grade L4 or L5 involved in the high-risk pregnancy or breast-feeding drug list. Results:Of the 151 kinds of infusion medicines commonly used in outpatient and emergency department in the sample hospital, a total of 118 kinds were with a specified level of pregnancy safety,which accounted for 78.15%,and a total of 86 kinds were with a clear indication of the safety level of lactation,which accounted for 56.95% of the total number of medicines. A total of 25 kinds of drugs labeled pregnancy safety grade D or X, which accounted for 16.56%, and 21 species were with lactation safety L4 or L5, which accounted for 13.90% of the total number of drugs. The drugs with high pregnancy or lactation risk in the outpatient and emergency department of the sample children's hospital were anti-tumor drugs,anti-infective drugs,some cardiovascular drugs and central nervous system drugs. Conclusion:There are still many deficiencies in the information about the safety of pregnancy or breast-feeding in the existing medicines used in the sample hospital,which need to be improved.