Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

OBJECTIVE To provide reference for safe drug use in the clinic by mining the adverse drug event （ADE） signals of 4 kinds of biological agents for the treatment of inflammatory bowel disease （IBD）. METHODS ADE data of infliximab， adalimumab， ustekinumab and vedolizumab were collected from the FDA adverse event reporting system between the first quarter in 2004 and the fourth quarter in 2022， and were mined by using reporting odds ratio （ROR） method and proportional reporting ratio （PRR） method. The system organ class （SOC） was used for the classification and statistics of drug ADE terminology. RESULTS & CONCLUSIONS A total of 65 173， 247 894， 37 596 and 6 134 ADE reports were retrieved for the above 4 biologic agents， involving 1 664， 1 731， 588， 303 ADE signals and 27， 27， 24， 26 SOC， respectively. The largest number of ADE reported of infliximab were various musculoskeletal and connective tissue diseases， and the signal intensity of disseminated tuberculosis was stronger. The largest number of ADE reported of adalimumab were systemic disease and various reactions at the administration site， and the signal intensity of papular at the injection site was stronger. The largest number of ADE reported of ustekinumab were various injuries， poisoning and operation complications， and the signal intensity of latent tuberculosis was slightly stronger. The largest number of ADE reported of vedolizumab were systemic diseases and various reactions at the administration site， and the signal intensity of shorter treatment response time was stronger. When clinically administering the four drugs， it is crucial to pay close attention to common ADEs and other ADE not mentioned in the drug label. For infliximab， clinicians should exercise caution due to the potential risk of synovitis and basal cell carcinoma； when prescribing adalimumab， caution should be exercised due to ADEs related to synovitis and hernia； for ustekinumab， the ADE associated with hepatobiliary diseases should be vigilant； for vedolizumab， clinicians should be vigilant for blood in the stool， increasing frequency of defecation. Except for ustekinumab， the other 3 biological agents also require attention for ADE associated with pregnancy.

Objective:To observe the influence of NOD-like receptor thermal protein domain associated protein 6 (NLRP6) on hepatic ischemia-reperfusion injury (IRI), and elucidate the related mechanism.Methods:Thirty C57BL/6 mice with body weight of (18.80±1.99) g, were divided randomly into 5 groups, with 6 mice in each group: the mice that experienced only exploratory laparotomy were Sham group; that only underwent an operation to establish a hepatic IRI model were IRI group; that were treated with tail intravenous injection of clodronate (Clo) liposomes before the establishment of hepatic IRI model were Clo group; that received tail intravenous injection of clodronate liposomes and transfusion of bone marrow derived macrophages (BMDM) before the operation were Clo+ BMDM group; that received preoperative tail intravenous injection of clodronate liposomes and transfusion of BMDM with NLRP6 knockdown were Clo+ NLRP6-knockdown group. Real time quantitative polymerase chain reaction analysis (RT-PCR) and Western blot were performed to analyze the expressions of pyroptosis related proteins and factors. Simulate a hypoxia/reoxygenation (H/R) model in vitro, and set up experimental groups: lipopolysaccharide (LPS) + adenosine triphosphate (ATP), LPS+ ATP+ NLRP6-knockdown, H/R, and H/R+ NLRP6-knockdown. The changes of expressions of pyroptosis related proteins and factors were detected by RT-PCR and Western blot. Expression of NF-κB in vivo and in vitro was measured.Results:Compared with those in Sham group, protein expressions of NLRP6, NLRP3, Caspase-1, gasdermin D (GSDMD), IL-1β and IL-18 were remarkably increased in IRI group, but the levels of these proteins were dramatically decreased in Clo group with the exhaustion of macrophages in comparison with in IRI group, which were significantly different statistically (all P<0.05). The levels of these proteins were enhanced again in Clo+ BMDM group with the reconstruction of macrophages in contrast to those in Clo group, while the enhancements were more obvious in Clo+ NLRP6-knockdown group comparing to those in Clo+ BMDM group, with significant differences (all P<0.05). In vitro, pyroptosis rate for LPS+ ATP group was (16.39±1.06)%, which was lower than (27.34±2.79)% for LPS+ ATP+ NLRP6-knockdown group, with a statistical significance ( P<0.05). Meanwhile, pyroptosis rate for H/R group was (20.59±5.66)%, also much more reduced than (37.76±2.00)% for H/R+ NLRP6-knockdown group ( P<0.05). Expressions of NLRP3, Caspase-1, GSDMD, IL-1β, IL-18 and NF-κB p65 in LPS+ ATP+ NLRP6-knockdown group were more elevated than in LPS+ ATP group, and these indices were also more enhanced in H/R+ NLRP6-knockdown group than which in H/R group. Compared to the Sham group, expression of NF-κB p65 significantly increased in IRI group, which was reversed in Clo group, but enhanced again in Clo+ BMDM group and reached a peak in Clo+ NLRP6-knockdown group. Conclusions:Macrophage plays a critical role in immune response to hepatic IRI, wherein NLRP6 functions specifically. NLRP6 acts to suppress inflammation during hepatic IRI through regulating macrophage pyroptosis via inhibiting NF-κB.

Objective:To explore risk factors of in-stent restenosis (ISR) after vertebral artery stenting (VAS) in patients with ischemic cerebrovascular disease.Methods:Case-control studies and cohort studies on risk factors for ISR after VAS in patients with ischemic cerebrovascular disease were searched from CNKI, VIP, Wanfang, Chinese Biomedical literature Database, PubMed, Embase and Cochrane Library. The retrieval time limit was the establishment of each database until May 31, 2021. Two researchers screened the literature and extracted relevant data. Newcastle-Ottawa Scale (NOS) was used to evaluate quality of the literature and RevMan 5.3 software was used for meta-analysis.Results:A total of 30 studies were included. Meta-analysis results showed that smoking [ OR=3.76, 95% confidence interval ( CI) : 2.43-5.82, P<0.01], diabetes ( OR=2.95, 95% CI: 2.15-4.06, P<0.01) , hypertension ( OR=2.55, 95% CI: 1.50-4.34, P=0.006) , hyperlipidemia ( OR=7.12, 95% CI: 3.46-14.68, P<0.01) , coronary heart disease ( OR=3.06, 95% CI: 1.10-8.47, P=0.03) , homocysteine ( OR=2.36, 95% CI: 1.30-4.27, P=0.005) , clopidogrel drug-related gene ( CYP2C19) mutation ( OR=3.04, 95% CI: 1.63-5.68, P=0.005) , lesion vessel diameter ( OR=3.43, 95% CI: 1.30-9.05, P=0.01) , residual stenosis ( OR=6.08, 95% CI: 3.28-14.07, P<0.01) ) , stent type ( OR=2.26, 95% CI: 1.18-4.36, P=0.01) , stent length ( OR=3.52, 95% CI: 2.34-5.30, P<0.01) were associated with ISR after VAS operation in patients with ischemic cerebrovascular disease. Conclusions:Postoperative smoking, history of diabetes mellitus, history of hypertension, history of hyperlipidemia, history of coronary heart disease, high level of homocysteine, CYP2C19 mutation, shorter lesion vessel diameter, postoperative residual stenosis, use of bare metal stents and longer stent length are risk factors for ISR after VAS in patients with ischemic cerebrovascular disease. Clinical medical staff should adjust the follow-up time of postoperative patients according to risk factors and formulate individualized strategies to prevent the occurrence of ISR.

Objective To understand the colonization status of Streptococcus pneumoniae and Haemophilus influenzae in nasopharynx of healthy infants in Wuhan. Methods Six vaccination clinics were randomly selected, and the nasopharyngeal specimens of healthy infants were collected and cultured for Streptococcus pneumoniae and Haemophilus influenza. Results The carrying rate of Streptococcus pneumoniae and Haemophilus influenzae in 998 healthy infants was 18.84% and 17.54%, respectively. The carrying rate of Streptococcus pneumoniae and Haemophilus influenzae within 6 months of age was 15.79% and 14.39%, and the carrying rate of Streptococcus pneumoniae and Haemophilus influenzae at 7-12 months old was 22.90% and 21.73%, respectively. The difference was statistically significant (Sp: χ²=5.60 P=0.02; Hi：χ²=8.98　P=0.00); The carrying rate of Streptococcus pneumoniae in urban and suburban areas was 18.08% and 19.78%, respectively, and the Haemophilus influenzae carrying rate was 17.18% and 17.98%, respectively. The differences were not statistically significant (Sp：χ²=0.47　P=0.50; Hi：χ²=0.11　P=0.74). The correlation coefficient (r value) of the age of the month and the carrying rate of sp and hi was 0.98 and 0.96, respectively. Conclusion The age of healthy infants in Wuhan was highly linearly and positively correlated with the carrying rate of Streptococcus pneumoniae and Haemophilus influenza.

Objective The study of capsaicin (CAP) on the effect and mechanism of indomethacin induced acute gastric mucosal injury in different period.Methods 80 SD rats were randomly divided into 8 groups with 10 rats in each group.The experiment was completed in two phases,and the Ⅰ period was 2 weeks,the Ⅱ period was 4 weeks.The Ⅰ period including group A1 (control group),group B1 (model group),group C1 (CAP group),group D1 (CAP + indomethacin group).The grouping method of the two periods were the same.The rats' gastric mucosa were damaged by indomethacin,and then killed the rats 4 hours later.Last,astric juice was collected to determine the total acidity of gastric acid,counted thegastric mucosal injury index,observed the gastric mucosa pathological injury,detected the expression of TRPV 1、CGRP、MDA、SOD and PGI2.Results The Ⅰ period:the gastric mucosa of group A1 and C1 had no damage.Group D1 compared with group B1,there was no significant difference in gastric mucosa injury (P ＞ 0.05),total acidity decreased significantly (P ＜ 0.05),MDA was no significant difference (P ＞ 0.05),SOD、PGI2 increased significantly (P ＜ 0.05),the expression of TRPV1、CGRP increased significantly (P ＜ 0.05).The Ⅱperiod:the gastric mucosa of group A2 and C2 had no damage.Group D2 compared with group B2,the gastric mucosa injury were significantly reduced (P ＜ 0.05),total acidity decreased significantly (P ＜ 0.05),MDA decreased significantly (P ＜ 0.05),SOD、PGI2 increased significantly (P ＜ 0.05),the expression of TRPV1、CGRP increased significantly (P ＜ 0.05).Conclusion There was no damage to the general morphology and histology of gastricmucosa in rats by intragastric CAP 1 mg/(kg· d) for 2 weeks and 4 weeks.2.It could prevent that indomethacininduced acute gastric mucosal injury in rats by pretreated with CAP 1 mg(kg· d) for 4weeks.

Objective To analyze the expression of long non-coding RNA ( lncRNA) in renal clear cell carcinoma ( RCCC ) , the association of lncRNA with RCCC, as well as the role of lncRNA in the diagnosis and treatment of RCCC.Methods Forty fresh RCCC tissues and their normal adjacent tissues were collected from March 2012 to June 2013, and total RNA was extracted using Trizol reagents, purified and tested by denaturing agarose gel electrophmesis and NanoDrop 1000.Through Arraystar Human LncRNA Microarray, the different expression of lncRNA between RCCC and normal adjacent tissues was screened. RT-qPCR was used to verify the expression of lncRNA in 40 pair RCCC tissues and normal adjacent tissues. The receiver-operating characteristic ( ROC ) curve was adopted to verify the diagnostic efficiency of the selected lncRNA.Results LncRNA expression profile showed 1 787 lncRNA with expression alteration in two fold or above, up-regulated and down-regulated candidate lncRNAs were 941 and 846 respectively. Compared with the adjacent tissues, NR_034095 and NR_038974 were up-regulated in RCCC, and ENST00000571724 and ENST00000566575 were down-regulated, which were consistent with the microarray analysis.By the ROC curves of NR_034095, NR_038974, ENST00000571724 and ENST00000566575 to discriminate the RCCC from normal adjacent tissue, the area under curve was 0.928 ( 95%CI 0.873 -0.984), 0.759 (95%CI 0.647-0.871), 0.833 (95%CI 0.747-0.919) and 0.887 (95%CI 0.815-0.959 ) , respectively.Conclusions NR _ 034095, NR _ 038974, ENST00000571724 and ENST00000566575 are significantly differently expressed in RCCC.The different expressed lncRNA might be closely related to the process of RCCC, and may be used as a new candidate target for molecular diagnosis and gene therapy of RCCC.

OBJECTIVE:To improve the accuracy of the Cetirizine hydrochloride syrup pediatric dose for children. METH-ODS:The dosage of Cetirizine hydrochloride syrup for children with chronic urticaria was accurately measured and compared with before and after pharmacists’intervention. RESULTS:The dosage before and after pharmacists’intervention was significantly high-er than prescribed dosage,the dosage after intervention was lower than before intervention,the differences were statistically signifi-cant(P<0.05). CONCLUSIONS:It is commonly existed that the dosage to children is higher than the prescribed dosage. It is sug-gested that doctors should strictly follow the printed label to make a prescription,pharmacists should strengthen the guidance and in-tervention on medication,and pharmaceutical manufacturers can manufacture suitable Cetirizine hydrochloride preparations special-ly for children to improve drug compliance and dosage accuracy.

Endoplasmic reticulum plays a key role in both basic structure formation and function performance of microenviron-ment. Endoplasmic reticulum homeostasis unbalance caused by endoplasmic reticulum stress has become a hot research topic in recent years. This paper focuses on the role of endoplasmic retic-ulum stress in ischemic stroke. Research progress of related sig-naling pathways were reviewed, especially mechanisms through which endoplasmic reticulum stress trigger the inflammatory reac-tion, so as to provide a new research method for prevention of is-chemic stroke.

Objective To analyze the epidemiological characteristics of mycoplasma pneumoniae (MP) infection among the out-patients and inpatients children in Shenzhen area during 2010-2012 and to explore the significance of the results of the laboratory routine tests in the diagnosis of MP infection .Methods The children patients with respiratory tract infection from 2010 to 2012 were selected and the MP infection and the non-MP infection were screened out .The epidemiological characteristics of gender ,age , etc .,among the children patients with MP infection during these 3 years were analyzed .The differences in the laboratory routine tests and high sensitivity C reactive protein (hsCRP) were compared between the MP infection and the non-MP infection .Results The positive detection rate of MP-DNA in males was slightly higher than that in females ,the difference had no statistical signifi-cance (P>0 .05);MP infection occurred in different age groups ,the positive detection rate of MP-DNA was lowest in the children patients aged <1 year old and highest in the children patients aged 3 - < 6 years (P< 0 .05);the routine laboratory tests and hsCRP level had no specificity in the diagnosis of MP infection .Conclusion The MP molecular epidemiology in Shenzhen area shows that MP infection has the seasonality ,the laboratory routine tests and hsCRP level can not be used as the basis of the MP la-boratory diagnosis .