Dysregulation of p53 and phosphoinositide (PIPn) signaling are both key drivers of oncogenesis and metastasis. Our recent findings reveal a previously unrecognized interaction between these pathways, converging in the nucleus to form a PIPn-p53 signalosome that modulates nuclear AKT activation and downstream signaling, thereby influencing cancer cell survival and motility. This review examines recent insights into nuclear PIPn signaling in the context of established roles for p53 in cell dynamics and migration while also deliberating current research on how nuclear PIPns interact with p53 to form signalosomes that affect cell motility. We emphasize the critical role of PIPns in stabilizing p53 and activating de novo nuclear AKT signaling, which subsequently modulates key motility-related pathways. Understanding the unique operation and function of the PIPn-p53 signalosome in nuclear phosphatidylinositol 3-kinase (PI3K)-AKT activation offers novel therapeutic strategies for controlling cancer metastasis by targeting pertinent interactions and events.
Humans ; Tumor Suppressor Protein p53/metabolism* ; Signal Transduction ; Cell Movement ; Cell Nucleus/metabolism* ; Phosphatidylinositols/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Animals ; Neoplasms/pathology* ; Phosphatidylinositol 3-Kinases/metabolism*

Purpose To investigate the expression and po-tential clinical value of heat shock protein 90α(Hsp90α)in co-lon adenocarcinoma.Methods The expression level of Hsp90αin colon adenocarcinoma and its relationship with clinicopatho-logical features,prognosis and immune cell infiltration were ana-lyzed by bioinformatics and immunohistochemistry.The prolifer-ation ability of colon cancer cells before and after Hsp90AA1 knockout was detected by CCK-8 cell proliferation assay and plate cloning assay.Results The bioinformatics tools showed that Hsp90AA1 was abnormally higher in colon cancer tissues than adjacent tissues,and the higher the expression level,the worse the prognosis of patients.The expression of Hsp90AA1 was positively correlated with the infiltration levels of CD4+T cells(Th2),CD8+T cells,myeloid inhibitory cells,Tregs cells,neutrophils,macrophages,M1 macrophages and M2 macropha-ges.Immunohistochemical results showed that the expression of Hsp90α in colon cancer tissues was significantly higher than in its adjacent tissues.The expression of Hsp90α was related to age(P＜0.05),not related to gender,tumor size,location,clini-cal classification,differentiation degree,tumor node metastasis,lympho-vascular invasion,perineural invasion(P＞0.05).The high expression of Hsp90α was an independent risk factor for the prognosis of colon cancer patients.The results of cell experi-ments showed that Hsp90AA1 knockout inhibited the growth and proliferation of colon cancer cells.Conclusion Hsp90α is highly expressed in colon adenocarcinoma,which may be a po-tential molecular marker for poor prognosis of colon adenocarci-noma.

Objective To construct a vimentin glycosylated mutant plasmid,and to study its impact on rat adrenal chromaffin cell (PC12) cell differentiation.Methods The vimentin glycosylated mutant plasmid was constructed,and the gel electrophoretic was performed and the sequencing identification was performed. The empty plasmid pcDNA3.1b (control group),vimentin plasmid (Vim group) and vimentin glycosylated mutant plasmid (Vim mut group) were used to transfect PC12 cells,which were cultured for 0,3 d in the con-dictions of treatment and non-treatment of exogenous oligosaccharides (Cyclo-ManN pro) respectively,and the cell differentiation records and quantitative analysis (the cell average neurite length and differentiated neu-rite cells percentage) were performed.Results A recombinant plasmid containing a glycosylation site muta-tion site 19(T-G),97(A-G),100(T-G) was successfully constructed (about 1404 bp in size).Before and after Cyclo-ManN pro treatment,the average neurite length of PC12 cells and the percentage of differentiated neu-rite cells in the Vim group were greater than those in the control group and the Vim mut group[(61.98±19.03)μm vs.(51.09±14.45)μm,(51.49±14.78)μm,(6.60±0.25)％ vs. (4.27±0.18)％,(4.76±0.33)％;(78.01±18.31)μm vs. (69.98±12.85)μm,(68.45±13.84)μm,(10.62±0.25)％ vs. (8.11±1.22)％,(5.89±0.60)％],the difference was statistically significant (P<0.05).Conclusion The glycosyla-tion modification of vimentin could be used for PC12 cell differentiation.

[摘 要] 目的：本研究旨在评估白蛋白紫杉醇+卡铂联合抗血管生成药物（nab-paclitaxel, carboplatin, antiangiogenic drug, NCA）方案用于既往治疗失败的晚期黑色素瘤患者的疗效和安全性。方法：收集2012年4月1日至2019年5月31日在北京大学肿瘤医院肾癌黑色素瘤科住院的黑色素瘤患者，回顾性分析NCA方案在既往治疗失败后的不可切除Ⅲ c期和Ⅳ期黑色素瘤患者中的疗效和安全性。主要终点指标为无进展生存期（PFS），次要指标为客观缓解率（ORR）、总生存期（OS）、疾病控制率（DCR）和不良反应。根据使用的抗血管药物分为恩度治疗组（n=73）和贝伐珠单抗治疗组（n=103），采用倾向性评分匹配以均衡不同抗血管生成药物组间基线变量的差异。结果：共计176例患者被纳入本项分析中。所有患者中位年龄51岁（范围为18~78岁）。Ⅳ期患者占97%，50%的患者LDH水平高于正常值，28%的患者存在肝转移。既往治疗线数占比分别为1线57%、2线33%、3~4线10%。所有患者的中位PFS为3.8个月（95%CI：3.0~4.6），中位OS为10.5个月（95%CI： 8.9~12.1）。2例患者获得完全缓解，9例患者获得部分缓解，全组的ORR为6%，DCR达70%。恩度治疗组和贝伐珠单抗治疗组的中位PFS分别为4.7个月（95%CI：3.5~5.9）和3.4个月（95%CI：3.0~4.6），两组中位OS分别为12.2个月（95% CI：11.1~13.2）和9.1个月（95%CI： 7.8~10.4）。对所有患者的年龄、性别、既往治疗线数和LDH水平进行倾向性评分匹配，贝伐珠单抗和恩度治疗组间PFS和OS差异无统计学意义。常见的不良反应包括脱发、周围神经病变、中性粒细胞减少、疲劳和恶心。26名（15%）患者由于不良反应停止了治疗。结论：白蛋白紫杉醇+卡铂联合抗血管生成药物对既往治疗失败的晚期黑色素瘤患者具有一定的疗效，不良反应可耐受。

AIM: To investigate the effect of ezetimibe combined with statins on residual lipoprotein-cholesterol (RLP-C) levels and major cardiovascular adverse events (MACE) in patients with acute coronary syndrome (ACS) after emergency intervention (PCI). METHODS: A total of 90 hospitalized patients with ACS and undergoing emergency PCI were randomly divided into two groups: 48 patients in the control group received atorvastatin, and 42 patients in the study group were additionally treated with ezetimibe. RLP-C level before and after treatment was detected. The occurrence of MACE events and adverse drug events during the treatment were obtained through regular follow-up. RESULTS: Compared with the control group, the level of RLP-C in the study group was significantly decreased (P<0.05), the incidence of MACE were significantly decreased (P<0.05), and adverse drug events were not increased. CONCLUSION: The combination therapy of ezedemibe and statins can reduce RLP-C level and MACE in ACS patients undergoing emergency PCI with less adverse reactions, which is worthy of promotion and application.

Objective To investigate the core emergency response capabilities of medical workers for corona virus disease 2019 (COVID-19) public health emergency, in order to provide references for improving emergency level. Methods By means of convenient sampling, the general information questionnaire and the medical staff's 2019-new coronavirus (2019-nCoV) core emergency capability questionnaire were used to conduct this survey, and the status of 2019-nCoV core emergency capability of 629 clinical medical staff was analysed. Results The score of core emergency response capability of medical staff for 2019-nCoV was (135.60±21.73)points, with a score rate of 73.3%; the score of preventive capability dimension was (11.69±1.96)points, with a score rate of 77.93%; the score of preparation ability dimension was (20.79±4.18)points, and the score rate was 69.30%; the score of rescue ability was (103.11±16.93)points, with a scoring rate of 73.57%. Conclusion The core emergency response capability of medical worker for 2019-nCoV and its dimensions are at a medium level. At the present stage, the training of core knowledge of medical personnel 2019-nCoV should be strengthened, effective measures should be taken to improve the alleviation of weakness in rescue, and the self-psychological adjustment of medical personnel should be strengthened to improve the core emergency response capability of medical worker.

Isovalerylspiramycin (ISP)Ⅰ, as a major component of bitespiramycin (BT), exhibits similar antimicrobial activities with BT and has advantages in quality control and dosage forms. It has been under preclinical studies. The existing ISPⅠ producing strain, undergoing three genetic modifications, carries two resistant gene markers. Thus, it is hard for further genetic manipulation. It is a time-consuming and unsuccessful work to construct a new ISPⅠ strain without resistant gene marker by means of the classical homologous recombination in our preliminary experiments. Fortunately, construction of the markerless ISPⅠ strain, in which the bsm4 (responsible for acylation at 3 of spiramycin) gene was replaced by the Isovaleryltansferase gene (ist) under control of the constitutive promoter ermEp*, was efficiently achieved by using the CRISPR-Cas9 gene editing system. The mutant of bsm4 deletion can only produce SPⅠ. Isovaleryltransferase coded by ist catalyzes the isovalerylation of the SPⅠat C-4" hydroxyl group to produce ISPⅠ. As anticipated, ISPⅠ was the sole ISP component of the resultant strain (ΔEI) when detected by HPLC and mass spectrometry. The ΔEI mutant is suitable for further genetic engineering to obtain improved strains by reusing CRISPR-Cas9 system.
CRISPR-Cas Systems ; Gene Editing ; Genetic Engineering ; Homologous Recombination

Objective: This study was designed to identify the relative factors, bacteriological profile and their antibiotic susceptibility pattern of neonatal sepsis. Methods: A retrospective survey was conducted on the clinical information, pathogen identification and antibiotic sensitivity results of 425 newborns with neonatal sepsis admitted to Nanjing Maternity and Child Health Care Hospital from 2010 to 2017. Of the 425 positive blood-cultures, 148 (34.82%) were early-onset neonatal sepsis (EOS) and 277 (65.18%) were late-onset neonatal sepsis (LOS). Clinical information and pathogen identification were compared between EOS and LOS. Antibiotic sensitivity of gram negative organisms (G^-) and gram positive organisms (G⁺) were also detected. Results: The rates of premature delivery (78.70%, n=218), low birth weights (67.15%, n=186) and cesarean delivery (59.57%, n=165) were significantly increased in LOS (P<0.05) compared with those rates in EOS, which were 41.89% (n=62), 37.84% (n=56) and 46.62% (n=69). Parturients fever (18.24%, n=27) and meconium like amniotic fluid (25.68%, n=38) were significantly increased in EOS (P<0.05) compared with those rates in LOS, which were 7.94% (n=22) and 5.42% (n=15). Among the identified pathogen, the incidence of G^- and G⁺ bacteria were 216 (50.83%) and 201 (47.29%) respectively, and the rest was Candida glabrata (1.88%, n=8). Escherichia coli 68 (16.00%) was the predominant isolate followed by Klebsiella pneumoniae (13.18%, n=56). The detection rate of Hemolytic staphylococcus (10.81%, n=16) was significantly increased in EOS (P<0.001) compared with LOS (1.44%, n=4). However, the incidence of Klebsiella pneumonia (5.88%, n=44) was higher in LOS (P=0.024) compared with EOS (8.11%, n=12). Most of the gram positive isolates exhibited high resistance to penicillin (90.32%-100.00%) and cephalosporin group antibiotics (25.00%-100.00%). Similarly, the majority of the gram negative isolates showed higher resistance to ampicillin (83.33%-100.00%), but susceptible to aminoglycosides (0-11.76%), quinolones (0-17.65%) and β-lactams (0-5.88%). Conclusion Among the study population, the percent of preterm, low birth weight and cesarean section were higher in LOS while parturients fever and meconium-like amniotic fluid were higher in EOS. The pathogens with the highest detection rate were Escherichia coli and Klebsiella pneumoniae. The results of antibiotic susceptibility test showed that common pathogens had high resistance to commonly used antibacterial drugs.

Objective To investigate the correlation between reproductive hormone concentration and the amplitude and latency of speech-evoked auditory brainstem response (speech-ABR) in young adults, and to explore the effects of reproductive hormone on the speech processing ability of young people.Methods Speech-ABR of thirty five normal hearing young adults, including seventeen females (27.29±1.83 years old) and eighteen males (28.17±2.50 years old) were recorded.The speech syllable /da/ was transmitted as a stimulus sound to the right ears through insert earphones in speech-ABR test.All participants had air conduction hearing thresholds of 20 dB HL or better across the standard audiometric frequencies (250~8 000 Hz) in both ears, and click-ABRs were also within normal limits.At the same time, the concentrations of estradiol and testosterone in the serum were examined.Results ① Females had a shorter latency than males in transient responses (waves V, A and O) and sustained responses (waves D, E and F) of speech-ABR (P<0.05, respectively).The amplitude of transient response (waves V and A) and sustained response (waves D, E and F) in females was also significantly larger than that in males (P<0.05, respectively), except for amplitude of peak O (P>0.05).The V/A slope in females was significantly steeper than that in males (P<0.05).② Estradiol levels in females (118.77±102.66 pg/ml) were significantly higher than that in males (52.91±14.77 pg/ml) (P<0.05), and the total testosterone concentration in females (457.65±140.82 pg/ml) was significantly lower than that in males (3 677.37±1 155.80 pg/ml) (P<0.05).③ A correlation analysis between speech-ABR and estradiol or total testosterone showed that all peak latencies of speech-ABR in transient responses (waves V, A and O) and sustained responses (waves D, E and F) were negatively correlated with the estradiol concentration (P<0.05 respectively), in which the correlation coefficient was between 0.2~0.4.All peak latencies of speech-ABR were positively correlated with the total testosterone concentration (P<0.05 respectively), in which the correlation coefficient was between 0.4~0.7.④ The amplitudes of speech-ABR increased with estradiol concentration growing, the wave V and estradiol concentrations were positively correlated (P<0.05).The estradiol concentrations showed a significant negative correlation with wave A, D, E, F and O wave (P<0.05 respectively), with a correlation coefficient between 0.2~0.7.On the contrary, the amplitudes of speech-ABR decreased with the increasing of total testosterone concentration, and the wave V, wave A, V/A slope and total testosterone concentration were moderately correlated (P<0.05),with a correlation coefficient between 0.4-0.6.The correlation between the amplitudes of D wave and total testosterone concentration was not statistically significant (P>0.05), and the correlation between wave E and wave F and total testosterone concentration was weakly correlated (P<0.05).In addition, the amplitudes of the wave O were also independent with testosterone levels (r=0.133, P>0.05).Conclusion There are correlations between the level of reproductive hormone and the amplitude and latency of speech-ABR.It is one of the reasons for the gender difference in the brainstem speech coding ability of normal young adult.

Objective To know the contamination status of Giardia lamblia and Cryptosporidium in drinking water of Jiangsu Province,so as to provide the evidence for producing hygiene and safety drinking water. Methods A total of 28 water plants of 13 cities in Jiangsu Province were selected,and the source water(10 L),chlorinated water(100 L)and tap water(100 L) were collected separately in each site. The water samples were then treated by filtration,washing,centrifuging concentration, immune magnetic separation,and immunofluorescent assay,to detect the numbers of Giardia cysts and Cryptosporidium oocysts. Results Totally 84 samples from 13 cities were collected,including 28 source water,28 chlorinated water and 28 tap water samples. Among the chlorinated water and tap water samples,no Giardia cysts and Cryptosporidium oocysts were found. Howev-er,Giardia cysts were detected in 3(10.71％,3/28)source water samples(Yancheng,Lianyungang,Changzhou cities),with the density of 1 cyst/10 L of all. Cryptosporidium oocysts were also detected in 3(10.71％,3/28)source water samples(Nan-jing,Zhenjiang,Yangzhou cities),with the density of 1 oocyst/10 L of all. Conclusions The source water in partial areas of Ji-angsu Province has been contaminated by Giardia and Cryptosporidium. To ensure the safety of drinking,the regulation of source water and surveillance of drinking water should be strengthened.