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 construct a postoperative nursing plan for liver transplant recipients using the NANDA international, nursing outcomes classification, nursing intervention classification (NANDA-I-NOC-NIC) link (referred to as NNN-link) as the theoretical framework, so as to optimize the nursing process after liver transplantation and improve the quality of nursing.Methods:This study retrospectively collected nursing diagnoses with a postoperative usage rate of over 50% from 300 liver transplant recipients at Shulan (Hangzhou) Hospital from January 2019 to December 2021, and matched nursing outcomes and measures based on the NNN-link theory framework. After two rounds of Delphi expert consultation and group discussion, the entry content was rated, discussed, and modified to form the final version of the postoperative NNN-link for liver transplant recipients.Results:In two rounds of expert consultation, the recovery rates were 96.67% (29/30) and 100.00% (29/29) , respectively. The expert authority coefficients were 0.83 and 0.84, respectively. The Kendall harmony coefficients for the second round were 0.50, 0.38, 0.35. The final postoperative NNN-link for liver transplant recipients included 15 nursing diagnoses, 42 nursing outcomes, and 106 nursing measures.Conclusions:The process of constructing the postoperative NNN-link for liver transplant recipients is scientific and reasonable, and the entries are highly specialized, which can provide reference for clinical nursing after liver transplantation.

Objective:To summarize the electroclinical characteristics of patients with epilepsy with myoclonic absence（EMA）and analyze the relationship with prognosis.Methods:Clinical data of 25 patients with EMA monitored at the pediatric EEG monitoring centers of Peking University People's Hospital and Peking University First Hospital between January 2012 and December 2022 were retrospectively analyzed and divided into three groups according to development before and after the onset of the disease to analyze the electroclinical characteristics and the relationship with prognosis.Results:There were 14 males and 11 females in 25 cases，and the median age of epilepy onset was 48（26，74）months.Sixteen cases in the group with normal development before and after the onset of epilepsy（group A），5 cases in the group with normal development before the onset of epilepsy but retarded development after the onset of epilepsy（group B），and 4 cases in the group with retarded development before and after the onset of epilepsy（group C）.The median age at onset was 62（36，82）months，34（21，66）months，and 26（20，32）months in the three groups，with 3，3，and 4 cases of early onset in each group，respectively.The EEG background activity slowed down in 10 cases，with 6，1 and 3 cases in the three groups，respectively.Interictal EEG was normal in 1 and abnormal in 24 cases，which showed generalized discharges，of which 11 cases showed coexisting focal discharges and generalized discharges.Among the focal discharges，there were cases in all three groups，involving the anterior-posterior，temporal and Rolandic regions.Fifteen cases had myoclonic absence（MA）induced by hyperventilation，with 10 cases in group A，4 cases in group B and 1 case in group C.The most prevalent concomitant seizure was myoclonic seizure（MS），with 9，3 and 2 cases in each group respectively.Statistically significant differences were seen in early onset and refractory EMA among the three groups（both P<0.05）.In further two by two comparisons，the proportion of early onset and drug refractory cases was greater in children in group C than in group A，with statistically significant differences（both P<0.017），and the difference in concomitant MS among the three groups was not statistically significant（ P>0.05）. Conclusions:The MA seizures in children with EMA are sensitive to hyperventilation.The common accompanying seizure is MS.Some children with EMA present with early onset and refractory epilepsy，with a tendency towards developmental epileptic encephalopathy.

Objective:To analyze the difference of clinical characteristics and outcomes of infants with moderate and severe pediatric acute respiratory distress syndrome(PARDS)diagnosed according to baseline oxygenation index(OI) in pediatric intensive care unit(PICU).Methods:Second analysis of the data collected from the "Efficacy of pulmonary surfactant (PS) in the treatment of children with moderate and severe ARDS" program.Retrospectively compare of the differences in clinical data such as general condition, underlying diseases, OI, mechanical ventilation, PS administration and outcomes among infants with moderate and severe PARDS divided by baseline OI who admitted to PICUs at 14 participating tertiary hospitals from 2016 to December 2021.Results:Among the 101 cases, 55 cases (54.5%) were moderate and 46 cases (45.5%) were severe PARDS.The proportion of male in the severe group (50.0% vs.72.7%, P=0.019) and the pediatric critical illness score(PCIS)[72 (68, 78) vs.76 (70, 80), P=0.019] were significantly lower than those in the moderate group, while there was no significant difference regarding age, body weight, etiology of PARDS and underlying diseases.The utilization rate of high-frequency ventilator in the severe group was significantly higher than that in the moderate group (34.8% vs.10.9%, P=0.004), but there was no significant difference in PS use, fluid load and pulmonary complications.The 24 h OI improvement (0.26±0.33 vs.0.04±0.34, P=0.001) and the 72 h OI improvement[0.34 (-0.04, 0.62) vs.0.15 (-0.14, 0.42), P=0.029)]in the severe group were significantly better than those in the moderate group, but there was no significant difference regarding mortality, length of hospital stay and intubation duration after diagnosis of PARDS between the two groups. Conclusion:In moderate and severe(divided by baseline OI) PARDS infants with invasive mechanical ventilation, children in severe group have better oxygenation improvement in the early stage after PARDS identified and are more likely to receive high frequency ventilation compared to those in moderate group.Baseline OI can not sensitively distinguish the outcomes and is not an ideal index for PARDS grading of this kind of patient.

In the COVID-19 epidemic prevention and control work, not only the safety management of in-hospital organ transplantation is facing severe challenges, but also a large number of patients at home after transplantation are in immunosuppressive state, and professional protection management is urgently needed. Since the outbreak of the epidemic, Shulan(Hangzhou)hospital fully identified the risks of transplant patients, established a special team, and formulated and implemented the control management plan for organ transplant patients based on the crisis leadership model. The control management plan has achieved staged results.From January 15 to March 2, 2020, 29 liver transplants and 31 kidney transplants were performed in our hospital. The remote health education of 1 002 patients after liver and kidney transplantation was completed. The goal of " zero infection" was achieved, and the protection management quality indicators were ideal.

Objective:To study the effect of melatonin (MEL) on the pyroptosis of hippocampus in neonatal rats with hypoxic-ischemic brain damage (HIBD), and the related mechanism.Methods:The animal model of HIBD was established by the modified Rice method.According to the random number table, a total of 105 Sprague-Dawley (SD) rats aged 7 days were divided into 7 groups (15 rats in each group): sham operation (Sham) group, model (HIBD) group, MEL treatment group (5, 10 and 20 mg/kg), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway inhibitor (LY294002) treatment group and MEL+ LY294002 group.The hippocampus neuronal morphology and the changes of nissl bodies were observed through HE staining and nissl staining.The mRNA expression levels of Nod-like receptor family 3 (NLRP3), apoptosis-associated speck-like protein containing a card (ASC), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β) and interleukin-18 (IL-18) in the left hippocampus of rats were detected by real-time fluorescence quantitative PCR.The protein expression level of the above indexes and the level of phosphorylated Akt (p-Akt) were measured by Western blot.Results:Compared with the Sham group, the number of cell layers in hippocampal CA1 region in the HIBD group decreased, the cell arrangement was irregular, and there were less nissl bodies.Besides, the mRNA expression levels of NLRP3 (1.98±0.08 vs.0.86±0.13), ASC (1.40±0.12 vs.0.81±0.07), Caspase-1 (1.46±0.10 vs.0.75±0.09), GSDMD (1.35±0.10 vs.0.81±0.10), IL-18 (1.23±0.08 vs.0.23±0.04), IL-1β (1.83±0.09 vs.0.57±0.08) and p-Akt (1.12±0.12 vs.0.54±0.07) in the HIBD group were significant higher than those in the Sham group (all P<0.05). Compared with the HIBD group, there were more cell layers in hippocampal CA1 region of the MEL group (10 mg/kg), the arrangement of cells was more regular, and the number of nissl bodies increased.The mRNA expression levels of NLRP3 (1.04±0.10), ASC (0.91±0.06), Caspase-1 (0.63±0.06), GSDMD (1.01±0.09), IL-18 (0.65±0.05) and IL-1β (0.63±0.10) in the MEL group were statistically significantly lower than those in the HIBD group (all P<0.05). Compared with the MEL group (10 mg/kg), the arrangement of cells in hippocampal CA1 region of the MEL+ LY294002 group was relatively disordered, the nissl bodies declined, the p-Akt protein level (0.87±0.09 vs.1.99±0.27) decreased significantly, and the Caspase-1(p20) protein level (0.85±0.09 vs.0.58±0.09) increased significantly (all P<0.05). Conclusions:MEL may inhibit the hippocampal pyroptosis in neonatal rats with HIBD by activating the Akt signaling pathway, thereby protecting the brain.

Objective:To explore the effects and mechanism of PR-957 on hypoxic-ischemic brain damage(HIBD) of newborn rats.Methods:A total of 54 rats aged seven days were recruited and randomly divided into sham operation group, HIBD group and PR-957 intraperitoneal group.HIBD model was established according to modified Rice method.PR-957 group was given intraperitoneal injection PR-957(20 mg/kg) after hypoxic-ischemic.Model group was intraperitoneally injected with equal volume of DMSO.Ligation or hypoxic treatment were not given in sham operation group.HE staining was applied to observe inflammation in cortex.Immunohistochemical analysis was adopted to observe the expression of interleukin(IL)-17 and IL-10 in brain tissue.Western blot was carried out to test the protein level of low molecular poly peptide 7 (LMP7), forkhead box P3(FOXP3), and retinoic acid-recepter-related orphan receptor gamma t(RORγt). The proportion of T helper cells 17(Th17)/Treg was detected by flow cytometry.Results:HE staining displayed that sham operation group brain structure was basically normal, HIBD group revealed significant inflammation in the left cerebral cortex, while some pathological improvement was observed in PR-957 group.Immunohistochemistry: IL-10 positive cells in left cortex of HIBD group [(12.11±3.73)%] were lower than sham operation group[(29.12±3.95)%] and PR-957 group[(22.61±6.59)%], and the differences were statistically significant (all P<0.05). IL-17 positive cells in the left cortex of HIBD group [(35.55±4.85)%] were higher than sham operation group [(8.48±2.58)%] and PR-957 group [(19.16±4.31)%], and the differences were statistically significant (all P<0.05). Western blot: the expression of LMP7 and RORγt in HIBD group (1.01±0.12, 0.71±0.10) were higher than those in sham operation group (0.50±0.10, 0.34±0.07) and PR-957 group (0.65±0.13, 0.54±0.07), and the differences were statistically significant ( P<0.05). The expression of FOXP3 in HIBD group (0.44±0.10) was lower than sham operation group (0.93±0.07) and PR-957 group (0.68±0.09), and the differences were statistically significant (all P<0.05). The flow cytometry of peripheral blood: the Th17/Treg ratio of HIBD group (0.66±0.24) was higher than sham operation group (0.20±0.09) and PR-957 group (0.45±0.18), and the differences were statistically significant (all P<0.05). Conclusion:PR-957 can regulate the immune balance of Th17/Treg cells and reduce the inflammatory in the brain tissues of HIBD newborn rats.

Objective: To analyze the activation of brain regions associated with olfactory in patients with mild cognitive impairment (MCI) by olfactory functional magnetic resonance imaging (fMRI). Methods: Twenty six patients with MCI were compared with twenty six controls in the dementia center of Tianjin HuanHu hospital in terms of olfactory function T&T testing, the differences between the activation of the whole brain and region of interest associated with olfactory (bilateral primary olfactory cortex(POC), bilateral hippocampus, bilateral orbital frontal gyrus) by olfactory stimulator using event correlation design for olfactory fMRI scanning. To analyze the correlation between the number of activator in POC and the threshold of olfactory discriminate as well as the severity of cognitive impairment.SPSS 19.0 software was used for the statistical analysis. Results: T&T olfactory testing revealed that MCI patients had higher scores than controls (3.57±1.29 (±s) vs 1.02±0.35, t=4.372, P<0.05). The activation range of whole brain in MCI patients was less than controls (pleasant odor (po) 147.36±21.45 vs 323.11±39.76, unpleasant odor (upo) 201.86±24.93 vs 447.73±57.22, t_po=4.241, t_upo=5.365, both P<0.05). The activation range of whole brain in inhaling unpleasant odor was more than pleasant odor in controls (447.73±57.22 vs 323.11±39.76, t=3.936, P<0.05). The number of activator in ROI_awo in MCI patients was less than controls (pleasant odor (po) 51.0[8.0, 109.0](M[P₂₅, P₇₅]) vs 135.0[21.0, 321.5], unpleasant odor (upo) 65.0[6.0, 158.0]vs 205.0[36.5, 491.0], Z_po=-2.199, Z_upo=-2.216, both P<0.05). The number of activator in POC in MCI patients was less than controls (pleasant odor (po) 19.0[4.0, 35.5]vs 46.0[9.0, 118.5], unpleasant odor (upo) 26.0[2.0, 51.0]vs 79.0[17.5, 189.0], Z_po=-1.898, Z_upo=-2.167, both P<0.05). The number of activator in POC was negatively correlated with olfactory discriminate threshold in MCI patients (r_po=-0.415, r_upo=-0.409, both P<0.05). The number of activator in POC was positively correlated with MoCA in MCI patients (r_po=0.289, r_upo=0.296, both P<0.05). Conclusion Olfactory fMRI can objectively assess the olfactory function in MCI, it is a imaging indicator with neuropsychological tests for detection in MCI, the number of activator in POC can reflect the severity of MCI.

Traditional Chinese medicine thinking is the core method of diagnosis and treatment of traditional Chinese medicine. Thus, cultivating the clinical thinking of traditional Chinese medicine in the orthopeadics department has become the importance. TCM tendon and muscle injuries were well characterised by the TCM, becoming an important part of TCM orthopedics., The tendon and muscle injuries were used to explore the application and cultivation of traditional Chinese medicine thinking. This will help to improve the clinical curative effect, complement the modern Chinese medicine.

Objective The advantages of the treating allergic rhinitis (AR) by sphenopalatine ganglion stimulation with acupuncture were evaluated.Methods Databases including CBMDisk, CNKI, WanFang, VIP, Cochrane Library, PubMed, ProQuest, ChiCTR, ISRCTN, ClinicalTrials.gov and CENTRAL were searched from the beginning of database established to Jan 2015. All issues from Jan 2004 to Jan 2015 published onjournals Chinese Acupuncture & Moxibustion,Shanghai Journal of Acupuncture and Moxibustion, Acupuncture Research,Journal of Clinical Acupuncture and Moxibustion,Chinese Journal of Integrated Traditional and Western Medicine and Chinese Journal of Otorhinolaryngology in Integrative Medicine were searched by hand at meantime. All data were extracted based on the inclusive and exclusive criteria which was pre-designed, the Revman5.3 was applied for meta-analysis, and the studies qualities were analyzed by grade score.Results 118 articles were collected, 7 studies that involving 1 230 patients met the inclusive criteria. The result indicated that the sphenopalatine ganglion stimulation with acupuncture as the main treatment of AR showed the better total response rate compared to conventional drugs, theOR(95%CI) was 3.22(1.81 - 5.75); however the change of total symptom score had no statistical significant difference, the MD(95%CI) was 0.69 (-0.56 - 1.93), the change of IgE had no statistical significant difference,theSMD(95%CI) was -0.07 (-0.97 - 0.83).Conclusion The main treatment on AR by sphenopalatine ganglion stimulation with acupuncture may has better efficacy than western medicine. But due to the methodological biases existed in most studies, future high-quality RCTs were needed to be included into Meta-analysis to test today’s study conclusion.