Ferroptosis, a programmed cell death modality discovered and defined in the last decade, is primarily induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System X_c^--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.

Objective To investigate the value of neutrophil to lymphocyte ratio(NLR)and lymphocyte to monocyte ratio(LMR)in the diagnosis and prognosis of patients with sepsis.Methods From January 2022 to December 2022,patients in the First Affiliated Hospital of Soochow University were recruited in this study,including 47 patients with sepsis(sepsis group),31 with infection but not diagnosed as sepsis(infection group),and 25 healthy individuals(control group)were simultaneously chosen.Patients with sepsis were assigned to non-shock group(32 cases)or shock group(15 cases),survivors group(38 cases)or deaths group(9 cases).Procalcitonin(PCT),C-reactive protein(CRP)and routine blood tests were analyzed and compared between groups.Spearman's correlation test was used to analyze the correlation among NLR,LMR and PCT,PCR,lymphocyte,monocyte,neutrophil,platelet and SOFA scores,the diagnostic value of NLR and LMR in sepsis was evaluated by plotting the receiver operating characteristic(ROC)curve.Results The NLR was 12.54(7.53,23.42)in sepsis group,3.85(1.83,5.64)in infection group,and 1.71(1.39,2.20)in normal control group.The corresponding LMR was 1.58(1.07,3.03),2.81(1.53,4.76),and 5.16(4.04,6.59),respectively.NLR was negatively correlated with LMR(rs=-0.469,P＜0.05).The NLR on day 7(NLR7)was 6.56(3.90,10.72)in the non-shock group and 15.20(7.53,27.31)in shock group.The corresponding △NLR7 was-1.64(-5.75,0.41)and 1.98(-0.48,13.79)in the two groups.The shock group had significantly higher △NLR7 than the non-shock group(P＜0.05).NLR7 was 7.10(4.09,12.96)in the survivors and 15.20(10.45,32.82)in the deaths group.The corresponding △NLR7 was-0.65(-5.58,1.58)and 5.02(-1.12,17.06)in the two groups.The deaths group had significantly higher △NLR7 than the survivors group(P＜0.05).The LMR on day 7(LMR7)was 2.22(1.64,3.78)in the non-shock group and 1.29(0.66,2.03)in shock group.The corresponding △LMR7 was 0.38(-0.37,1.17)and-0.19(-0.78,0.25)in the two groups.The shock group had significantly lower △LMR7 than the non-shock group(P＜0.05).LMR7 was 2.12(1.49,3.42)in the survivors group and 1.09(0.53,1.78)in the deaths group.The deaths group had significantly lower LMR7 than the survivors group(P＜0.05).The AUC of NLR was 0.959 1(95％CI:0.910 5-1.000 0)in diagnosis of sepsis.The best cut-off value was 4.16.The A UC of LMR was 0.913 6(95％CI:0.846 4-0.980 8)in diagnosis of sepsis.The best cut-off value was 3.21.Conclusions NLR and LMR can be used to evaluate the severity and prognosis of patients with sepsis.These two markers may play a role in the diagnosis of sepsis.

Objective To investigate the value of neutrophil to lymphocyte ratio(NLR)and lymphocyte to monocyte ratio(LMR)in the diagnosis and prognosis of patients with sepsis.Methods From January 2022 to December 2022,patients in the First Affiliated Hospital of Soochow University were recruited in this study,including 47 patients with sepsis(sepsis group),31 with infection but not diagnosed as sepsis(infection group),and 25 healthy individuals(control group)were simultaneously chosen.Patients with sepsis were assigned to non-shock group(32 cases)or shock group(15 cases),survivors group(38 cases)or deaths group(9 cases).Procalcitonin(PCT),C-reactive protein(CRP)and routine blood tests were analyzed and compared between groups.Spearman's correlation test was used to analyze the correlation among NLR,LMR and PCT,PCR,lymphocyte,monocyte,neutrophil,platelet and SOFA scores,the diagnostic value of NLR and LMR in sepsis was evaluated by plotting the receiver operating characteristic(ROC)curve.Results The NLR was 12.54(7.53,23.42)in sepsis group,3.85(1.83,5.64)in infection group,and 1.71(1.39,2.20)in normal control group.The corresponding LMR was 1.58(1.07,3.03),2.81(1.53,4.76),and 5.16(4.04,6.59),respectively.NLR was negatively correlated with LMR(rs=-0.469,P＜0.05).The NLR on day 7(NLR7)was 6.56(3.90,10.72)in the non-shock group and 15.20(7.53,27.31)in shock group.The corresponding △NLR7 was-1.64(-5.75,0.41)and 1.98(-0.48,13.79)in the two groups.The shock group had significantly higher △NLR7 than the non-shock group(P＜0.05).NLR7 was 7.10(4.09,12.96)in the survivors and 15.20(10.45,32.82)in the deaths group.The corresponding △NLR7 was-0.65(-5.58,1.58)and 5.02(-1.12,17.06)in the two groups.The deaths group had significantly higher △NLR7 than the survivors group(P＜0.05).The LMR on day 7(LMR7)was 2.22(1.64,3.78)in the non-shock group and 1.29(0.66,2.03)in shock group.The corresponding △LMR7 was 0.38(-0.37,1.17)and-0.19(-0.78,0.25)in the two groups.The shock group had significantly lower △LMR7 than the non-shock group(P＜0.05).LMR7 was 2.12(1.49,3.42)in the survivors group and 1.09(0.53,1.78)in the deaths group.The deaths group had significantly lower LMR7 than the survivors group(P＜0.05).The AUC of NLR was 0.959 1(95％CI:0.910 5-1.000 0)in diagnosis of sepsis.The best cut-off value was 4.16.The A UC of LMR was 0.913 6(95％CI:0.846 4-0.980 8)in diagnosis of sepsis.The best cut-off value was 3.21.Conclusions NLR and LMR can be used to evaluate the severity and prognosis of patients with sepsis.These two markers may play a role in the diagnosis of sepsis.

Objective:To investigate the efficacy and safety of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis.Methods:A retrospective analysis was carried out on 46 patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis who received endovascular treatment at the Strategic Support Force Medical Center from January 2015 to August 2022. Twenty-seven patients underwent balloon angioplasty alone and 19 patients underwent acute stent implantation. The baseline characteristics, modified thrombolysis in cerebral infarction (mTICI) score of the responsible vessels, modified Rankin scale (mRS) score 90 days after operation, incidence of symptomatic intracranial hemorrhage and mortality of the two groups were evaluated.Results:The proportion of effective recanalization of the offending vessels (mTICI≥2b) in the acute stenting group was slightly higher than that in the balloon angioplasty group (16/19 vs. 81.5%), but the difference was not statistically significant ( P>0.05). Besides, there was no significant difference in the median of mRS between the acute stenting group [3.0(0, 4.0)] and the balloon angioplasty group [4.0(1.0, 5.0)] 90 days after operation ( P>0.05). In terms of safety, the incidence of symptomatic intracranial hemorrhage and mortality were comparable between the two groups ( P>0.05). Conclusions:The effect of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis is not inferior to that of balloon angioplasty, and it does not increase the risk of intracranial bleeding complications.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To evaluate the efficacy of platelet-monocyte aggregates (PMA) in the clinical diagnosis of sepsis.Methods:From January 2022 to December 2022, patients in the First Affiliated Hospital of Soochow University were recruited in this study, among which 41 were with sepsis (sepsis group), 41 patients had infection but were not diagnosed as sepsis (infection group), and 25 healthy individuals (healthy control group) were simultaneously chosen. Patients with sepsis were divided into the shock group (14 cases) and the non-shock group (27 cases). PMA of all subjects were measured by Beckman Coulter Navios Flow Cytometry and detection of procalcitonin(PCT), C-reactive protein (CRP) and platelet (PLT).The differences of the two indexes between the different groups were compared by nonparametric test. Spearman′s correlation test was used to analyze the correlation among PMA, PCT, CRP and PLT. The diagnostic value of PMA in sepsis was evaluated by drawing the receiver operating characteristic (ROC) curve. Kaplan-Meier survival curve was used to compare the survival time of patient with different PMA. Results:The PMA in the sepsis group, infection group and healthy control group were 52.66% (27.10%, 81.09%), 37.22% (26.52%, 54.56%) and 15.94% (15.10%, 17.02%), respectively. For the three groups, PCT levels were 3.10 (0.23, 15.35)μg/L, 0.15 (0.08, 0.79)μg/L and 0.02 (0.02, 0.02)μg/L, CRP levels were 106.6 (35.87, 175.60)mg/L, 76.45 (27.20, 110.10)mg/L and 1.26 (0.94, 2.42) mg/L, and the PLT counts were 116.00 (90.25, 204.30)×10 9/L, 192.00 (147.30, 333.00)×10 9/L and 199.50 (178.00, 252.80)×10 9/L. The values for PMA, PCT and CRP levels were significantly higher in the septic group compared to the healthy controls (the U values were 0.00, 5.00 and 1.00, P<0.001). But the PLT for the septic group was lower than that from the healthy control ( U=47.00, P<0.05). The differences in PCT and PLT were statistically (the U values were 84.50 and 176.50, P<0.05), but there was no significant difference between the PMA and CRP(the U values were 255.00 and 210.00, P>0.05) for the two groups. PMA was positively correlated with PCT( rs=0.562, P<0.001) and CRP( rs=0.447, P<0.001) in patients. The levels of PMA in shock and non-shock groups were 83.54% (76.51%, 86.82%) and 43.75% (21.59%, 62.83%) respectively ( U=12.00, P<0.05). The AUC of PMA in diagnostic of sepsis was 0.750(95% CI 0.657-0.843), the best cut-off value was 37.99%. Survival curve analysis showed that the survival time was significantly lower in the PMA≥37.99% group ( χ 2=4.805, P<0.05). Conclusion:PMA holds significant clinical reference for sepsis diagnosis and has the potential to serve as a biomarker in sepsis diagnostic procedures.

ObjectiveTo investigate the comorbidity of community patients with stroke in Songjiang District， Shanghai， determine the prevalence and characteristics of comorbidities and influencing factors， and provide scientific evidence for prevention and treatment of stroke. MethodsA natural population-based cohort study was conducted in several communities of Songjiang District from April 2016 to October 2017. Questionnaire survey， physical examination and biochemical examination were conducted in the cohort population to understand the comorbidity of 1 523 patients with stroke at baseline. ResultsThe prevalence of comorbidities in community patients with stroke was 74.0%， which was higher in female （76.36%） than that in male （70.76%）. The average number of comorbidities was 2.62±1.56， which was significantly higher in female （2.70±1.58） than that in male （2.52±1.54） （t=-2.31， P=0.021）. In this population， the most common two-comorbidity combination was hypertension+central obesity （35.85%）， and the most common three-comorbidity combination was hypertension+dyslipidemia+central obesity （17.20%）， with statistically significant differences by gender and age groups （P<0.05）. Multivariate analysis showed that age ≥65 years， urban population， hyperhomocysteinemia （HHcy）， and family history of hypertension were risk factors associated with comorbidities， whereas educational level of middle school and high school， and physical exercise 1‒3 days per week were protective factors. ConclusionPrevalence of comorbidity is high in community patients with stroke in Songjiang District， Shanghai. It is suggested to control blood pressure and body weight， adopt healthy lifestyle and take comprehensive prevention and treatment measures in this population.

Bone homeostasis is a relative balance between bone formation and resorption. Signal transducer and activator of transcription 3 (STAT3), which is closely related to bone homeostasis, takes part in multiple intracellular and extracellular signal pathways. STAT3 participates in the process of osteoblast differentiation regulated by several factors. It can also maintain bone homeostasis by regulating the recruitment, differentiation and activation of osteoclasts. In addition, STAT3 is involved in the interaction between osteoblasts and osteoclasts. Patients with STAT3 mutations can have several inherited bone metabolism diseases. Furthermore, STAT3 plays a critical role in load-driven bone remodeling. Mechanical stimulation promotes osteoblast differentiation and bone formation through activating or enhancing STAT3 expression during bone remodeling process. This review summarizes the participation of STAT3 in maintaining bone homeostasis together with its possible mechanisms and discusses the connection between STAT3 and mechanical stimulation in bone remodeling, so as to provide a potential pharmacological target for the treatment of bone diseases.

As a traditional Chinese medicine， Ziziphi Spinosae Semen （ZSS） has the functions of tonifying liver， tranquilizing heart， astringent sweat and producing body fluid， which is used to treat neurasthenia， insomnia， dreaminess， debility， night sweat and so on. With the rapid and constant development of ZSS resource industry and its medicinal value， a large number of by-products and waste generated in the production and processing process， resulting in serious environmental problems. In general， the utilization rate of ZSS resources was still not high. Based on this， the chemical components and potential resources of ZSS were systematically combed from the perspective of the medicinal parts and bioactive components in this paper， and the authors had summarized that the widely application of ZSS and its by-products （fruit， leaf， root， etc.） in the fields of food， medicine， functional food and other areas was discovered and summarized as feed， feed additives， activated carbon， organic fertilizer， etc. In addition， this paper systematically summarized the current environmental protection problems of the industry， and put forward suggestions for improvement， aiming at reducing environmental pollution and improving the utilization efficiency of resources， so as to provide reference and basis for the comprehensive utilization of ZSS and its by-products， and promote the green， economical and double-effect development of the industry.