Triple-negative breast cancer (TNBC) represents an aggressive breast cancer subtype with poor prognosis and limited targeted treatment options. This investigation examined the anti-cancer potential of Caerulomycin A (Cae A), a natural compound derived from marine actinomycetes, against TNBC. Cae A demonstrated selective inhibition of viability and proliferation in TNBC cell lines, including 4T1, MDA-MB-231, and MDA-MB-468, through apoptosis induction. Mechanistic analyses revealed that the compound induced sustained endoplasmic reticulum (ER) stress and subsequent upregulation of C/EBP homologous protein (CHOP) expression, resulting in mitochondrial damage-mediated apoptosis. Inhibition of ER stress or CHOP expression knockdown reversed mitochondrial damage and apoptosis, highlighting the essential role of ER stress and CHOP in Cae A's anti-tumor mechanism. Both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) decreased in TNBC cells following Cae A treatment, indicating reduced mitochondrial respiratory and glycolytic capacities. This diminished energy metabolism potentially triggers ER stress and subsequent apoptosis. Furthermore, Cae A exhibited significant anti-tumor effects in the 4T1 tumor model in vivo without apparent toxicity. The compound also effectively inhibited human TNBC organoid growth. These results indicate that Cae A may serve as a potential therapeutic agent for TNBC, with its efficacy likely mediated through the disruption of glucose metabolism and the induction of ER stress-associated apoptosis.
Humans ; Endoplasmic Reticulum Stress/drug effects* ; Triple Negative Breast Neoplasms/genetics* ; Apoptosis/drug effects* ; Cell Line, Tumor ; Female ; Animals ; Glucose/metabolism* ; Mice ; Cell Proliferation/drug effects* ; Transcription Factor CHOP/genetics* ; Antineoplastic Agents/pharmacology* ; Mitochondria/metabolism* ; Mice, Inbred BALB C

Objective To explore the differences in tremor characteristics between patients with primary Parkinson's disease(IPD),essential tremor(ET),and Parkinson's disease developed from essential tremor(ET-PD).Method Thirty IPD patients,30 ETs,and 20 ET-PD patients were included,and the frequency,contraction pattern,and presence of harmonics of static and postural tremors were compared among the three groups.Results There were statistically significant differences(P<0.01)among the IPD group,ET group,and ET-PD group in terms of age of onset,disease course,and the unified Parkinson's disease rating scale(UPDRS)score.There were statistically significant differences(P<0.05)in the average frequency of stationary tremors,average frequency of postural tremors,rate of alternating tremors in stationary state,rate of alternating tremors in postural state,and rate of harmonic occurrence in stationary state among the IPD group,ET group,and ET-PD group,as well as in the rate of harmonic occurrence in postural state(P<0.05).Conclusion The IPD group,ET group,and ET-PD group each have significant differences in tremor characteristics.The ET-PD group has both characteristics and uniqueness,and tremor analysis can help identify this disease.

Objective: First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients. Methods: Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/ placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2). Results: Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP. Conclusion Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer.

Objective: First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients. Methods: Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/ placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2). Results: Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP. Conclusion Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer.

AIM:To investigate whether the expression of perilipin 2(PLIN2)in renal tubular cells could predict a decline in renal function in diabetic kidney disease(DKD)patients,and to explore the potential mechanisms in-volved in renal tubular cell injury induced by PLIN2 during the progression of DKD.METHODS:Control individuals(n=12)and DKD patients(n=51)were enrolled in this retrospective cohort study.Demographic and laboratory data were col-lected.A simplified linear mixed-effects model was applied to assess the estimated glomerular filtration rate(eGFR)slope.The relationship between PLIN2 and renal function decline in DKD patients was predicted by Spearman correlation analysis and a generalized linear model.BKS-db/db diabetic mice and streptozotocin-induced diabetic mice were used.Primary renal tubular cells were treated with glucose and transfected with small interfering RNA or plasmid.Western blot-ting and immunofluorescence staining were used to detect PLIN2 expression.Lipid droplets were stained with oil red O.The oxygen consumption rate(OCR)of mitochondria was measured using an extracellular flux analyser.RESULTS:The expression of PLIN2 was markedly higher in the tubules of DKD patients than in those of control subjects.After 24(12,39)months of follow-up,the eGFR slope of DKD patients was-7.42(-19.77,-2.09)mL/(min·1.73 m2·year).An in-crease in the baseline percentage of PLIN2-positive tubules was significantly associated with the eGFR slope during the fol-low-up period[hazard ratio(HR)=1.90,95%confidence interval(CI):1.00～3.58],indicating that tubular PLIN2 could predict a decrease in renal function in DKD patients.Both the accumulation of lipid droplets and the expression of PLIN2 were markedly greater in the tubules of diabetic mice than in those of control mice.Glucose treatment induced lipid droplet accumulation and PLIN2 expression in renal tubular cells.Knockdown of PLIN2 significantly alleviated glucose-in-duced lipid droplet accumulation,whereas PLIN2 overexpression aggravated glucose-induced lipid droplet accumulation.The decrease in mitochondrial OCR in renal tubular cells induced by glucose treatment was alleviated after PLIN2 knock-down.However,overexpression of PLIN2 directly decreased the mitochondrial OCR.CONCLUSION:The PLIN2 ex-pression in tubules predicts a decline in renal function in patients with DKD.The PLIN2 suppresses mitochondrial aerobic respiration and contributes to the accumulation of lipid droplets in renal tubular cells to promote the progression of DKD.

Objective: First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients. Methods: Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/ placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2). Results: Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP. Conclusion Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer.

Objective To analyze the relationship between the expression of nuclear factor κB(NF-κB)family of transcription factors(P50)and NF-κB inhibitory protein-α(IκB-α)in cervical lesions and human papilloma virus 16(HPV16)-positive cervical cancer.Methods Cervical tissue samples were collected from 106 patients with HPV16-positive cervical cancer,52 patients with high-grade squamous intraepithelial neoplasia(HSIL),and 43 patients with low-grade squamous intraepithelial neoplasia(LSIL)admitted to Tumor Hospital Affilated to Natong University from March 2017 to February 2019.Normal cervical tissue samples were collected from 80 patients who underwent total hysterectomy for adenomyosis during the same period.The expression levels of NF-κB P50 and IκB-α in different cervical tissue samples were determined by immunohistochemistry.The expression of NF-κB P50 and IκB-α in different cervical tissue was compared.The relationship between NF-κB P50 and IκB-α expression levels and pathological features of cervical cancer patients was investigated.Cox regression analysis was used to assess the factors affecting the prognosis of patients with HPV16-positive cervical cancer.The relationship between NF-κB P50 and IκB-α expression levels and the prognosis of HPV16-positive cervical cancer patients was analyzed.Results The positive expression rate of NF-κB P50 and the negative expression rate of IκB-α from high to low was:cervical cancer tissue,HSIL tissue,LSIL tissue,and normal cervical tissue(P<0.01).The positive expression rate of NF-κB P50 and the negative expression rate of IκB-α in HPV16-positive cervical cancer patients with the largest tumor diameter≥4 cm,clinical stage III/IV,lymph node metastasis,poorly differentiated,and vascular invasion were significantly higher than those in the patients with the tumor largest diameter<4 cm,clinical stage I/II,no lymph node metastasis,moderate/well differentiated,and no vascular invasion(P<0.05).Cox regression analysis showed that clinical stage(OR:2.546,95%CI:1.054-3.672),lymph node metastasis(OR:2.734,95%CI:1.469-4.183),degree of differentiation(OR:3.257,95%CI:2.015-6.432),positive expression of NF-κB P50(OR:4.025,95%CI:2.765-8.436),and negative expression of IκB-α(OR:4.368,95%CI:3.104-10.254)were independent influence factors for the prognosis of patients with HPV16-positive cervical cancer factor(P<0.05).By the end of the follow-up,the overall survival rates of NF-κB P50 positive patients and NF-κB P50 negative patients were 73.68%and 92.59%,respectively.There was a statistically significant difference between the survival curves of patients with positive NF-κB P50 expression and those with negative NF-κB P50 expression(P<0.05).The overall survival rates of IκB-α positive patients and IκB-α negative patients were 100.00%and 76.34%,respectively.There was a statistically significant difference between the survival curves of patients with positive IκB-α protein expression and those with negative expression of IκB-α protein(P<0.05).Conclusion There are high positive expression rate of NF-κB P50 and high negative expression rate of IκB-α in the cancer tissue of HPV16-positive cervical cancer patients.The expression of NF-κB P50 and IκB-α has a certain correlation with clinicopathological characteristics and prognosis of HPV16-positive cervical cancer patients.

Objective:To explore the correlation between socioeconomic status (SES) and diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D).Methods:A total of 276 T2D patients admitted to the Second Affiliated Hospital of Nanjing Medical University from January to June 2020 were enrolled in this cross-sectional study. The estimated glomerular filtration rate (eGFR) was calculated according to the urinary albumin/creatinine ratio (UACR) and the chronic kidney disease epidemiology collaboration equation(CKD-EPI formula) based on serum creatinine. The patients were divided into simple T2D group (184 cases) and DKD group (92 cases). Collect demographic and laboratory examination data, record education, income and occupation, and calculate standardized SES scores. According to SES scores, subjects were divided in three levels: SES≤9, SES≥10-≤12, and SES≥13. Student's t test was used for comparison of measurement data with normal distribution between two groups, and one-way ANOVA was used for comparison between multiple groups. Non-normal distribution was represented by M( Q1, Q3), and rank-sum test was used for comparison between groups. Counting data were expressed as frequency or percentage, and chi-square test was used for comparison between groups. Bofferoni test was further used for pairwise comparison of indicators with statistical significance among multiple groups. Spearman correlation analysis was used to analyze the correlation between variables. The risk factors were analyzed by binary Logistic regression. Results:The age of the subjects was (53.37±10.68) years, men accounted for 55.8% (154/276), the duration of diabetes was 60.00 (12.00, 134.00) months, and eGFR was (97.56±21.15) mL/(min·1.73 m 2). In simple T2D group and DKD group, prevalence of hypertension were 39.7% (73/184) and 57.6% (53/92), systolic blood pressure were (129.43±14.92) mmHg and (139.29±17.61) mmHg, diastolic blood pressure were (81.86±10.06) mmHg and (87.74±11.19) mmHg, serum albumin were (45.74±4.15) g/L and (43.99±5.05) g/L, triglycerides were (1.82±1.24) mmol/L and (2.64±2.92) mmol/L, high density lipoprotein cholesterol were (1.17±0.37) mmol/L and (1.07±0.26) mmol/L, serum uric acid were (298.44±90.73) μmol/L and (336.22±94.01) μmol/L, serum creatinine were (62.83±14.45) μmol/L and (87.75±57.37) μmol/L, eGFR were (102.6±14.28) mL/(min·1.73 m 2) and (87.47±28.04) mL/(min·1.73 m 2), UACR were (7.60 (4.63, 13.15)) mg/g and (93.95 (47.25, 310.25)) mg/g. Prevalence of hypertension, systolic blood pressure, diastolic blood pressure, triglycerides, serum uric acid, serum creatinine, UACR in DKD group were higher than those in simple T2D group. Serum albumin, high density lipoprotein cholesterol and eGFR in DKD group were lower than those in simple T2D group. There was significant difference between the two groups ( χ2=7.95, t values were 4.87, 4.40, 3.04, 3.26, 2.30, 3.22, 5.56, 5.95, Z=13.07, P values were 0.005, <0.001, <0.001, 0.003, 0.001, 0.022, 0.001, <0.001, <0.001, and <0.001, respectively). The number of males in the three groups with SES ≥13 group, SES≥10-≤12 group, SES ≤9 group were 61 (81.3%, 61/75), 55 (59.8%, 55/92), 38 (34.9%, 38/109), respectively. The number of cases with smoking history were 42 (56.0%, 42/75), 41 (44.6%, 41/92), 35 (32.1%, 35/109), respectively. The number of cases with drinking history were 38 (50.7%, 38/75), 32 (34.8%, 32/92), 26 (23.9%, 26/109), respectively. The ages were (47.77±10.76), (52.76±11.22), (57.74±7.96) years old, respectively. Body mass index (BMI) were (26.17±3.87), (24.96±3.93), (24.27±4.89) kg/m 2, respectively. High density lipoprotein cholesterol (HDL) were (1.03±1.03), (1.16±0.41), (1.21±0.32) mmol/L, respectively. Serum uric acid were (336.56±82.05), (293.78±94.78), (307.99±96.53) μmol/L, respectively. EGFR were (105.03±19.72), (99.77±19.44), (90.57±21.49) mL/(min·1.73 m 2),respectively.The difference between groups were statistically significant (χ 2=39.79, 10.55, 14.08, F=22.69, 4.03, 6.20, 4.53, 12.02, P values were <0.001, 0.005, 0.001, <0.001, 0.019, 0.002, 0.012, and <0.001, respectively). Pairwise comparison shows that male and eGFR in SES ≤9 group were lower than those in SES ≥13 group and SES≥10-≤12 group, age in SES ≤9 group was higher than that in SES ≥13 group and SES≥10-≤12 group. The difference was statistically significant (all P<0.05). Smoking history, alcohol history and BMI in SES ≤9 group were lower than those in SES ≥13 group, and the high density lipoprotein cholesterol in SES ≤9 were higher than that in SES ≥13 group. The difference was statistically significant (all P<0.05). Male, alcohol history and serum uric acid in SES≥10-≤12 group were lower than those in SES ≥13 group, and age and high density lipoprotein cholesterol in SES≥10-≤12 group were higher than those in SES ≥13 group. The difference was statistically significant (all P<0.05). Spearman correlation analysis showed that SES in T2D was positively correlated with male, smoking history, alcohol history, BMI, serum uric acid and eGFR ( r values were 0.38, 0.20, 0.24, 0.16, 0.13 and 0.31, P values were <0.001, 0.001, <0.001, 0.008, 0.028, and <0.001, respectively), and negatively correlated with age, high density lipoprotein cholesterol and UACR ( r values were -0.35, -0.24 and -0.14, P values were <0.001, <0.001, and 0.017, respectively). Logistic regression analysis showed that SES (OR=2.71,95% CI:1.10-6.68, P=0.031) was associated with T2DM combined with DKD. The risk of developing DKD increased when the SES was ≤9. Conclusion:The SES in patients with type 2 diabetes is closely related to DKD. Low SES may be a new risk factor for DKD in type 2 diabetic patients.

Objective:To evaluate the prognostic value of combined detection of platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and squamous cell carcinoma antigen (SCC) for patients with advanced cervical squamous cell carcinoma undergoing radical radiotherapy.Methods:Clinical data of 127 patients with advanced cervical squamous cell carcinoma who received radical radiotherapy in the Affiliated Tumor Hospital of Nantong University from January 2016 to February 2019 were analyzed retrospectively. The enrolled cases were divided into the survival group and death group according to the survival at the end of 3 years after treatment. The laboratory indexes of peripheral blood were collected before treatment, PLR and NLR were calculated, and the differences of clinical parameters were compared between two groups. The prediction model was established, and the prediction efficiency of PLR, NLR and SCC alone and combined prediction models for 3-year overall survival (OS) in patients with advanced cervical squamous cell carcinoma was compared through the ROC curve. Univariate and multivariate analyses of prognosis were carried out by binary logistic regression model.Results:A total of 127 patients with advanced cervical squamous cell carcinoma were included in the study. There were 96 cases in the survival group and 31 cases in the death group. There were significant differences between two groups in FIGO stage, longest diameter of tumor, lymph node metastasis, PLR, NLR and SCC (all P<0.05). The area under ROC curve (AUC) of PLR, NLR and SCC was 0.660, 0.712 and 0.700, respectively. The AUC of PLR+NLR+SCC combined prediction model was increased to 0.784. Logistic multivariate analysis showed that FIGO Ⅲ, FIGO Ⅳ, lymph node metastasis, PLR≥205.555, NLR≥3.060 and SCC≥6.950 ng/ml were the independent risk factors for 3-year OS in patients with advanced cervical squamous cell carcinoma (all P<0.05). Conclusions:PLR, NLR and SCC have good value in predicting the 3-year OS of patients with advanced cervical squamous cell carcinoma, and the combined prediction model of PLR+NLR+SCC has higher prediction value.

Objectives:To investigate the epidemiological features and associated factors of chronic renal insufficiency (CRI) in Binhai county from Jiangsu province.Methods:This is a cross-sectional study including individuals aged≥18 years old and participating in health examinations of Binhai county from January to December 2018. Medical records were collected to analyze the epidemiology of CRI [estimated glomerular filtration rate <60 ml·min -1·(1.73 m 2) -1]. Multivariate logistic regression was used to analyze the associated influencing factors of CRI. Results:A total of 395 541 individuals residing in Binhai county were enrolled, with 190 258 males (48.1%) and age of (55.34±15.12) years old. The overall crude prevalence of CRI was 2.04% (8 065/395 541, 95% CI 2.00%-2.08%) in this adult population. Furthermore, the age- and gender-standardized overall prevalence of CRI was 1.22% (95% CI 1.18%-1.25%), with a rate of 1.47% (4 676/205 283, 95% CI 1.42%-1.52%) in women and a rate 0.95% (3 389/190 258, 95% CI 0.91%-1.00%) in men. There was a strong positive correlation between the risk of CRI and age (per 10-year increase, OR=2.449, 95% CI 2.402-2.497). Compared with individuals <30 years old, the OR of CRI in individuals aged 60-69, 70-79 and ≥80 years old were 3.827 (95% CI 3.010-4.864), 12.004 (95% CI 9.457-15.239) and 44.636 (95% CI 35.187-56.622) respectively. Females ( OR=1.142, 95% CI 1.083-1.203), increasing systolic blood pressure (per 10 mmHg increase, OR=1.062, 95% CI 1.048-1.076), increasing heart rate (per 10-beat/min increase, OR=1.071, 95% CI 1.044-1.098), elevating triglyceride (per 1.33 mmol/L increase, OR=1.140, 95% CI 1.119-1.162), elevating fasting blood glucose (5.6-6.9 mmol/L/<5.6 mmol/L, OR=1.158, 95% CI 1.086-1.233; ≥7 mmol/L/<5.6 mmol/L, OR=1.387, 95% CI 1.296-1.484) and central obesity ( OR=1.126, 95% CI 1.068-1.187) were independent risk factors for CRI. Conclusions:The age- and gender-adjusted prevalence of CRI in adults in Binhai county is 1.22%. Older age, females, central obesity, and high levels of triglyceride, systolic blood pressure, heart rate and fasting glucose are independent associated factors of CRI.