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

Acute respimtory distress syndrome(ARDS)is an acute diffuse inflammatory lung injury caused by various internal and external lung injury factors.It has complex pathogenesis,rapid onset and high mortality,which seriously endangers human life and health.Pulmonary fibrosis is one of the important pathologic processes of ARDS occurrence and development,and it is also an important cause of death in ARDS patients.To a certain extent,the severity of pulmonary fibrosis in ARDS is determined by the dynamic balance of macrophage-fibroblast interactions.Therefore,this article aims to review the interaction mechanism of macrophage-fibroblasts in the pro-cess of ARDS pulmonary fibrosis,and provide new methods and ideas for the diagnosis and treatment of ARDS pul-monary fibrosis.

Objective To investigate the effect of baicalin(BA)regulating cyclic adenosine phosphate(cAMP)/protein kinase A(PKA)/cAMP response elemen-binding protein(CREB)pathway on skin barrier function in eczema rats.Methods SD rats were randomly divided into the control group(NC group),the model group,the low-dose BA group(BA-L group,25 mg/kg),the medium-dose BA group(BA-M group,50 mg/kg),the high-dose BA group(BA-H group,100 mg/kg),the prednisone group(PNS group,25 mg/kg),the BA-H+cAMP inhibitor(SQ22536)group(100 mg/kg+2.13 mg/kg)and the BA-H+PKA inhibitor(H-89)group(100 mg/kg+5 mg/kg),12 animals in each group.Except for the NC group,eczema rat model was constructed in the other groups.Two days after successful modeling,drug administration was performed in groups.Changes of eczema area and severity index(EASI)score,transcutaneous water loss(TEWL)and cuticle water content(WCSC)were detected.Enzyme-linked immunosorbent assay(ELISA)was used to detect levels of immunoglobulin E(IgE),interferon-γ(IFN-γ)and interleukin-4(IL-4)in rat serum and the expression of cAMP protein in rat back lesions.HE staining was used to detect pathological changes of skin lesions on the back of rats.Western blot assay was used to detect aquaporin 3(AQP3),cathelicidin related antimicrobial peptide(CRAMP),p-PKA,p-CREB protein expression in rat back lesions.Results Compared with the NC group,rats had serious pathological lesions on the back of the tested area,increased EASI score,TEWL,IgE and IL-4 levels,and decreased WCSC,IFN-γ,AQP3,CRAMP,cAMP,p-PKA and p-CREB protein levels in the model group(P<0.05).Compared with the model group,pathological lesion of the tested area in the back of rats was relieved,and EASI score,TEWL,IgE and IL-4 levels were decreased,WCSC,IFN-γ levels,AQP3,CRAMP,cAMP,p-PKA and p-CREB protein were increased in the BA-L group,the BA-M group,the BA-H group and the PNS group(P＜0.05).Changes of above indexes in the BA-L group,the BA-M group,the BA-H group were dose-dependent.SQ22536 or H-89 attenuated the improvement effect of high dose BA on skin barrier function in eczema rats.Conclusion BA may improve skin barrier function in eczema rats by activating cAMP/PKA/CREB signaling pathway.

Objective:To assess the diagnostic performance of serum anti-toxocara immunoglobulin G (anti-T-IgG) in ocular toxocariasis (OT) patients.Methods:A diagnostic tests. A total of 109 patients (109 eyes) with clinically-suspected OT who treated in Department of Ophthalmology of Xuzhou First People’s Hospital from June 2015 to December 2022 were included. Patients were divided into two groups, 76 with OT and 33 with non-OT, according to the clinical manifestations and Goldmann-Witmer coefficient. Paired serum and intraocular fluid samples from each patient were collected and analyzed for specific anti-T-IgG using enzyme linked immunosorbent assay. Mann-Whitney test was performed for comparison between groups. The area under the receiver operating characteristic curve (ROC) was used to assess the diagnostic performance of serum anti-T-IgG. Kappa analysis was performed to examine the consistency of serum or intraocular fluid anti-T-IgG positive rate with OT diagnostic result. Spearman’s rank correlation test was performed to assess the association.Results:Compared with the non-OT group, the proportions of children and history of exposure to cats and dogs ( χ2=9.785, 12.026) were significantly higher in OT group, and the differences were statistically significant ( P<0.01). The positive rate ( χ2=24.551) and U value ( Z=-4.379) of serum anti-T-IgG in OT group were higher than those in non-OT group, and the differences were statistically significant ( P<0.000 1). The recommended serum anti-T-IgG cut-off value of 11 U had 0.72 sensitivity, 0.79 specificity, 0.89 positive predictive value, 0.55 negative predictive value, and 0.77 area under the ROC with 95% confidence interval ( CI) 0.669-0.860. Correlation analysis showed that serum anti-T-IgG was positively correlated with intraocular fluid anti-T-IgG ( r s=0.520, 95% CI 0.363-0.648, P<0.000 1). The Kappa values of serum and intraocular fluid anti-T-IgG positive rate with OT diagnosis were 0.457 (95% CI 0.292-0.622) and 0.711 (95% CI 0.582-0.840), respectively. The Kappa value of serum anti-T-IgG positive rate with OT diagnosis was lower than that of intraocular fluid. Conclusion:The sensitivity and specificity of serum anti-T-IgG and the consistency between serum anti-T-IgG positive rate and OT diagnosis are low, suggesting that serum anti-T-IgG level cannot be used as a basis for OT diagnosis.

OBJECTIVE To explore the role of Th1/Th2 immune balance in the signal transduction of H1R, PAR-2/TRPV1 itch signal pathway and the intervention mechanism of Fuxian lotion. METHODS There were 60 BALB/c mice randomly divided into 6 groups after 3 days of adaptive feeding, with 10 mice in each group, which were blank control group, model control group, high, medium and low dose group of Fuxian lotion(36, 12, 4 mg·cm-2) and positive drug control group(1 mg·cm-2). Except for the blank control group, all other groups were sensitized with 7% and 0.5% 2,4-dinitrochlorobenzene acetone olive oil solution for multiple times. The abdomen and ears of mice in the blank group were coated with acetone solution for control. The drug was administered 24 hours after challenge, twice a day for 10 consecutive days. The ear thickness and the degree of mice ear swelling were measured and scored. The times of scratching the ears of mice were counted. The spleen index was calculated. HE staining was used to observe the pathological changes in mice ear tissue. The serum TNF-α, IL-1β, IL-31 levels were detected by ELISA, the mRNA level of the above immune factors was detected by realtime PCR, and the expression of H1R, PAR-2 and TRPV1 was detected by immunohistochemistry. RESULTS Compared with the blank control group, the ear thickness, ear allergic reaction score, scratching index, the spleen index of mice in the model control group was significantly increased(P<0.01), the TNF-α, IL-1β, IL-31 protein level and mRNA level were significantly increased(P<0.01), and the contents of H1R, PAR-2 and TRPV1 were significantly increased(P<0.01). There were obvious eczema like pathological changes in chronic dermatitis. Compared with the model control group, Fuxian lotion could effectively reduce the degree of auricle swelling, the score of ear allergic reaction, scratch index and spleen index, significantly reduce the levels of TNF-α, IL-1β, IL-31 protein level and mRNA level(P<0.01). The content of H1R in the high dose group of Fuxian lotion, the medium dose group of Fuxian lotion and the positive drug control group was significantly reduced(P<0.01), and the content of PAR-2 and TRPV1 in all dose groups of Fuxian lotion and the positive drug control group were significantly reduced(P<0.01). CONCLUSION Fuxian lotion can improve chronic dermatitis and eczema by regulating the Th1/Th2 immune balance, down regulating the characteristic immune factor TNF-α, IL-1β, IL-31 and interfering with the itch signal pathway H1R, PAR-2/TRPV1 transmission, so as to anti-itching and inhibit inflammatory response.

Objective To analyze the epidemic characteristics of imported dengue fever in Pudong New Area of Shanghai from 2008 to 2020，and to explore its prevention and control strategy and measures． Methods The data of dengue fever cases in Pudong New Area from 2008 to 2020 were collected from the China Information System for Disease Control and Prevention. Descriptive epidemiological method was used to analyze the epidemic characteristics. Results A total of 45 cases of dengue fever were reported in Pudong during 2008-2020, all the cases were mild, and no deaths were reported．The male-to-female ratio was 2.46:1. The group aged 20-49 years accounted for 86.67%．The most common occupation was commercial service personnel and cadres (25 cases, accounting for 55.56%). The peak of incidence was from July to October with a total of 35 cases (77.78%). All the cases were imported from abroad, mainly from Southeast Asia and South Asia (43 cases, 95.56%). 15 cases (33.33%) had been ill before entry. 22 cases (48.89%) were first treated in tertiary hospitals. The median time intervals from onset to first clinic visit, from first clinic visit to diagnosis, and from onset to diagnosis were 1.0 d, 5.0 d, and 7.0 d, respectively. Serotypes of dengue virus were mainly Type I, Type III and Type II, which were 9 cases, 7 cases, and 6 cases, respectively. Conclusion The epidemic situation of dengue fever in Pudong New Area from 2008 to 2020 is relatively stable, all imported from abroad. The focus of the prevention and control is to promote the health education for overseas travelers, strengthen the monitoring sensitivity at border ports, enhance the diagnostic level of medical institutions, and timely find and report cases.

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.

ObjectiveTo investigate current status of hospital infection management in psychiatric hospitals in the Ningxia Hui Autonomous Region， so as to provide references for improving the level of hospital infection management of psychiatric hospitals. MethodsIn December 2020， on-site supervision was conducted on hospital infection management in all 9 psychiatric hospitals in the Ningxia Hui Autonomous Region， meantime， the self-compiled questionnaire on hospital infection management status was used for investigation. ResultsAmong the selected hospitals， nine （100.00%） psychiatric hospitals had the main hospital leaders in charge of hospital infection management， five （55.56%） hospitals had established a hospital infection management committee， six （66.67%） hospitals had established an independent hospital infection management department， and one （11.11%） hospital had developed all 13 systems mentioned in the questionnaire related to hospital infection management and job responsibilities. In terms of hospital infection management staff， there were 23 staff members in the nine psychiatric hospitals， including 3 in the specialty （13.04%） and 20 in the part-time setting （86.96%）. The score of the implementation of the basic system of hospital infection management in nine hospitals was （3.28±2.22）. ConclusionThe system specification related to hospital infection management in the Ningxia Hui Autonomous Region psychiatric hospitals needs to be improved and further strengthened， the professionalism of hospital infection management personnel needs to be improved.

Salvianolic acid B (SAB) is an active phytocomponent of a popular Chinese herb called Radix Salvia militiorrhiza with numerous biological properties. The anti-psoriasis activity of SAB was examined by evaluating various psoriasis inflammatory and keratin markers against imiquimod (IMQ)-induced psoriasis on BALB/c mice. Totally 50 healthy BALB/c mice were evenly divided into 5 groups including control, drug control (SAB; 40 mg/kg), IMQ-induced psoriasis (5%), IMQ exposure and treated with SAB (40 mg/kg), or standard methotrexate (MTX; 1 mg/kg). Mice supplemented with either SAB or MTX significantly lowered the values of psoriasis area severity index (PASI), erythema, scaling, skin thickness, inflammatory markers (interleukin [IL]- 22/23/17A/1β/6) and lipid peroxidation product (malondialdehyde). Also, IMQ exposed BALB/c mice treated with SAB or MTX display lesser histopathological changes with enhanced antioxidant activities (catalase, superoxide dismutase). Moreover, the protein expression of keratin markers (K16 and K17) and phosphatidylinositol- 3-kinase (PI3K)/protein kinase B (Akt) signaling proteins (pAkt/Akt and pPI3K/PI3K) were significantly downregulated after administration with SAB and MTX as compared with IMQ induced mice. Taking together, SAB and MTX significantly ameliorate psoriatic changes by inhibiting psoriatic inflammatory and keratin markers through abolishing PI3K/Akt signaling pathway. However, further studies (clinical trials) are needed to confirm the anti-psoriatic property of SAB before recommending to psoriasis patients.

Salvianolic acid B (SAB) is an active phytocomponent of a popular Chinese herb called Radix Salvia militiorrhiza with numerous biological properties. The anti-psoriasis activity of SAB was examined by evaluating various psoriasis inflammatory and keratin markers against imiquimod (IMQ)-induced psoriasis on BALB/c mice. Totally 50 healthy BALB/c mice were evenly divided into 5 groups including control, drug control (SAB; 40 mg/kg), IMQ-induced psoriasis (5%), IMQ exposure and treated with SAB (40 mg/kg), or standard methotrexate (MTX; 1 mg/kg). Mice supplemented with either SAB or MTX significantly lowered the values of psoriasis area severity index (PASI), erythema, scaling, skin thickness, inflammatory markers (interleukin [IL]- 22/23/17A/1β/6) and lipid peroxidation product (malondialdehyde). Also, IMQ exposed BALB/c mice treated with SAB or MTX display lesser histopathological changes with enhanced antioxidant activities (catalase, superoxide dismutase). Moreover, the protein expression of keratin markers (K16 and K17) and phosphatidylinositol- 3-kinase (PI3K)/protein kinase B (Akt) signaling proteins (pAkt/Akt and pPI3K/PI3K) were significantly downregulated after administration with SAB and MTX as compared with IMQ induced mice. Taking together, SAB and MTX significantly ameliorate psoriatic changes by inhibiting psoriatic inflammatory and keratin markers through abolishing PI3K/Akt signaling pathway. However, further studies (clinical trials) are needed to confirm the anti-psoriatic property of SAB before recommending to psoriasis patients.