Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relatively low. This is closely related to the immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs). Our previous work identified that a phosphoglycerate mutase 1 (PGAM1) allosteric inhibitor, HKB99, exerts a range of anti-tumor activities in lung cancer. Here, we found that upregulation of PGAM1 correlates with increased levels of M2-like tumor-associated macrophages (TAMs) in human colon cancer samples, particularly in liver metastatic tissues. HKB99 suppressed tumor growth and metastasis in cell culture and syngeneic tumor models. M2-polarization, induced by colon cancer cell co-culture, was reversed by HKB99. Conversely, the increased migration of colon cancer cells by M2-TAMs was remarkably restrained by HKB99. Notably, a decrease in TAM infiltration was required for the HKB99-mediated anti-tumor effect, along with an increase in CD8⁺ T cell infiltration. Moreover, HKB99 improved the efficacy of anti-PD-1 treatment in syngeneic tumors. Overall, this study highlights HKB99's inhibitory activity in TAM-mediated colon cancer progression. Targeting PGAM1 could lead to novel therapeutic strategies and enhance the effectiveness of existing immunotherapies for colon cancer.

Objective:To evaluate the safety and effectiveness of capsule endoscopy for the diagnosis of intestinal diseases in children.Methods:Clinical data of 113 pediatric patients who received capsule endoscopy in Xi'an Children's Hospital from October 2018 to September 2020 were retrospectively analyzed. The completion rate, passage time of stomach and small intestine, lesion detection rate, adverse reactions and complications of capsule endoscopy were analyzed.Results:Among 113 pediatric patients, 78 (69.03%) were male and 35 (30.97%) were female. The age was (99.8±44.7) months (9-195 months), and 31 (27.43%) were under 7 years old. The minimum weight was 9 kg and the minimum height was 70 cm. Eighty-seven pediatric patients (76.99%) swallowed capsules orally (the oral group) with the minimum age of 4 years and 3 months. Capsules were implanted in 26 pediatric patients (23.01%) under gastroscopy (the gastroscopic group), with the maximum age of 9 years and 2 months. Unexplained abdominal pain (47.79%) and unexplained gastrointestinal bleeding (31.89%) were common in the pediatric patients. The completion rate of capsule endoscopy was 97.35% (110/113), and the detection rate of lesions in small intestine was 31.81% (35/110). The passage time of small intestine in the gastroscopic group was significantly longer than that of the oral group (461.04±129.27 min VS 288.23±107.84 min, t=5.646, P<0.01). There was no significant difference in the passage time of stomach or small intestine among different genders, different ages or different endoscopic examination results ( P>0.05). The positive results of capsule were not correlated with the method of ingestion ( P=0.401, OR=2.562, 95% CI:0.284-23.077), gender ( P=0.154, OR=2.352, 95% CI:0.726-7.616), age ( P=0.949, OR=1.007, 95% CI:0.816-1.242), examination reason ( P=0.246) or small intestine passage time ( P=0.219, OR=1.003, 95% CI:0.998-1.008). No complications such as capsule retention occurred in any pediatric patient. Conclusion:Capsule endoscopy in children is noninvasive, rapid and simple, which can improve the diagnostic rate of small intestinal diseases in children, and can be further promoted in pediatric patients.

When this paper was first published the following ethical statement was omitted in error: This study was approved by the Ethics Committee of AAALAC (NO. 001488) and carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of Tianjin Institute of Pharmaceutical Research. The authors would like to apologise for any inconvenience caused. DOI of original article: https://doi.org/10.1016/j.chmed.2018.12.002

When this paper was first published the following ethical statement was omitted in error: This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of Tianjin Institute of Pharmaceutical Research. The authors would like to apologise for any inconvenience caused.

Ralstonia solanacearum strain PRS-84 used in this study was isolated from diseased Pogostemon cablin plants in our previous study.The competent cells of R.solanacearum strain PRS-84 were transformed by electroporation with Tn5 transposon and then were plated on TTC agar plates containing kanamycin to select for kanamycin-resistant colonies.The detection of kanamycin-resistant gene in kanamycin-resistant colonies was performed by PCR.Further,the flanking fragments of Tn5 transposon insertion site in the mutants were amplified by inverse PCR,and the flanking fragments were sequenced and analyzed.The results indicated that the kanamycin-resistant colonies were obtained in the transformation experiment of R.solanacearum strain PRS-84 by electroporation with Tn5 transposon.A specific band of approximately 700 bp was amplified by PCR from kanamycin-resistant colonies.The flanking sequences of Tn5 transposon insertion site in the transformants were obtained by inverse PCR.After sequencing and sequence analysis of Tn5 transposon insertion site in mutants,we preliminarily speculated that the Tn5 transposon inserted in the typ A gene,rec O gene and gid A gene in three mutants,respectively.A random mutagenesis system of R.solanacearum strain PRS-84 by electroporation with Tn5 transposon has been established,and the Tn5 insertion mutants have been obtained.This study might facilitate the creation of mutant library and the discovery of the virulence gene of R.solanacearum isolated from P.cablin.
DNA Transposable Elements ; Electroporation ; Genes, Bacterial ; Mutagenesis, Insertional ; Pogostemon ; microbiology ; Ralstonia solanacearum ; genetics ; Virulence

Objective To observe the effects of Batroxobin Injection on thromboembolic cerebral stroke by magnetic resonance imaging (MRI) and TTC staining.Methods Rat model ofthromboembolic stroke was prepared after the left middle cerebral artery was occluded by autologous blood clots,and 32 rats with successful operation were divided into four groups according to the degree of neurological deficit:model group,Batroxobin Injection low and high dose (0.3,1.0 BU/kg) group,and rt-PA (9 mg/kg) group,with eight rats in each group,and other eight rats in Sham group.Rats were administered 1 h after modeling by tail iv method.At 6 h after administration,neurological deficit score and MRIincluding SE-T2WI and DWI sequence scanning were measured.At 24 h after administration,the brain was cut for TTC staining to measure the infarct area,and blood FIB was measured.Results Compared with model group,Batroxobin Injection 0.3 BU/kg treatment for 24 h (P ＜ 0.05),1 BU/kg treatment for 6 and 24 h (P ＜ 0.05,0.01) could significntly improve the neurological function scores of rats.MRIresults showed that Batroxobin Injection at dose of 0.3 and 1 BU/kg significantly reduced the lesion range (P ＜ 0.05 and 0.01).Results of TTC stain showed that Batroxobin Injection at dose of 0.3 and 1 BU/kg significantly reduced the infarct size (P ＜ 0.05).Batroxobin Injection at doses of 0.3 and 1 BU/kg can significantly lower plasma FIB concentration (P ＜ 0.05,0.01,0.001) 6 and 24 h after administration.Conclusion Batroxobin Injection can improve the damaged neural function,reduce scope of lesions,decrease plasma fibrinogen,with protective effects for cerebral ischemia in rats.

The effects of the feed attractants on Whitmania pigra were studied. The average weight of Wh. pigra were 5.0 g. Arginine was selected as feed attractants, xanthan gum was selected as feed substrate. The times of Wh. pigra going into the inducing room were recorded. The water temperature was 22-25 degrees C during the whole experiment. Arginine that had better inducing effect was chosen to carry on in the gradient experiment. The results showed that the best inducing effect was found when the added amount of arginine was 0.3%, which was close to the arginine content of the natural body fluid of Wh. Pigra and Bellamya purificata, 2.97 mg x g(-1).
Animal Feed ; analysis ; Animals ; Arginine ; analysis ; metabolism ; Body Weight ; Feeding Behavior ; Leeches ; growth & development ; physiology

Objective To investigate the effect of adenosine disodium triphosphate(ADT) on myocardial infarction in rats.Methods The a-cute myocardial infarction rat model was induced by ligation of the left anterior descending coronary artery.The model rats were divided into five groups randomly:model group, ADT 1, 2, 4 mg· (kg· d) -1 and enal-aprilat 10 mg· ( kg· d) -1 , and the other 8 rats received sham surgery.The effect of ADT on myocardial infarction rats included left ventricular of configuration , the degree of myocardial hypertrophy and pulmonary ede-ma, scope of myocardial infarction and myocardial remodeling were deter-mined by color Doppler echocardiography , hemodynamic , heart weight , lung water content and the content of collagen type ⅠandⅢafter contin-uous dosing for 30 days.Results Compared with model , ADT can im-prove left ventricular function of myocardial infarction rats , improve sig-nificantly left ventricular ejection fraction significantly , reduce left ven-tricular end-diastolic pressure and cavity size , the lung water content and the range of myocardial infarction , inhibit ventricular remodeling , etc.Conclusion ADT can improve the cardiac function after myocardial infarction in rats.

PURPOSE: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory enzyme expressed in atherosclerotic plaques. We investigated the association of circulating Lp-PLA2 with characteristics of vulnerable coronary atherosclerotic plaques. MATERIALS AND METHODS: We recruited 113 patients with either unstable angina (UA, n=59) and stable angina (SA, n=54) by coronary angiography. Thirty-six healthy subjects served as controls. Intravascular ultrasound (IVUS) was used to evaluate the characteristics of coronary atherosclerotic plaque, and serum Lp-PLA2 concentration was measured as well. RESULTS: Lp-PLA2 concentration was significantly higher in both UA and SA patients [(396+/-36) microg/L and (321+/-39) microg/L, respectively] compared with the controls [(127+/-49) microg/L, p<0.01], and higher in UA than SA group. IVUS findings showed that remodeling index (RI) (0.91+/-0.15 vs. 0.85+/-0.11, p=0.005) and eccentricity index (EI) (0.73+/-0.16 vs. 0.65+/-0.22, p=0.039) were larger in UA than in SA group, and fibrous caps were thicker in SA than UA group [(0.91+/-0.23) mm vs. (0.63+/-0.21) mm, p=0.032]. Moreover, Lp-PLA2 correlated positively with EI (r=0.439, p<0.01) and RI (r=0.592, p<0.05) in UA group. There was an inverse relationship between Lp-PLA2 and fibrous cap thickness in both UA (r=-0.587, p<0.001) and SA (r=-0.318, p<0.05) groups. The independent risk factors in UA group were Lp-PLA2 (OR=1.055, 95% CI: 1.03-1.08, p=0.013), LDL-cholesterol (OR=0.032, 95% CI: 0.00-0.05, p=0.041) and fibrous cap thickness (OR=0.008, 95% CI: 0.00-0.45, p=0.019). Lp-PLA2 was strongly associated with both EI and fibrous cap thickness in both groups. CONCLUSION: Serum level of Lp-PLA2 is associated with both eccentricity index and fibrous cap thickness in both UA and SA groups. Elevated levels of circulating Lp-PLA2 might to be a strong risk factor and more serious for unstable angina than stable angina.
1-Alkyl-2-acetylglycerophosphocholine Esterase/*blood ; Adult ; Aged ; Aged, 80 and over ; Angina, Stable/*blood/enzymology/*pathology ; Angina, Unstable/*blood/enzymology/pathology ; Coronary Angiography ; Coronary Artery Disease/*blood/enzymology/*pathology ; Female ; Humans ; Male ; Middle Aged

OBJECTIVETo investigate the gene mutation in a Chinese pedigree and one sporadic case with pachyonychia congenita type I(PC-1), as well as to explore the relationship between the genotype and phenotype.

METHODSThe whole coding region of the KRT16 and KRT6A genes were amplified by long-range polymerase chain reaction (PCR). Six patients with PC-1 were studied, five of them were from a pedigree and the other one was sporadic. One unaffected member in the pedigree and 100 unrelated healthy individuals were also studied in order to exclude polymorphism. PCR products were directly sequenced to detect the mutation.

RESULTSNo mutations in the KRT16 gene were observed. All patients harbored a mutation in the KRT6A gene. All five patients in the pedigree had a mutation at codon 465 (TAC to CAC) which substitutes tyrosine (Y) by histidine (H). In the sporadic patient, codon 171 (AAC) was mutated to GAC, which changes the asparagines (N) to aspartic acid (D). No such mutations were found in the unaffected member of the pedigree and the 100 unrelated controls. The mutation of Y465H is located at the end of 2B and N171D at the beginning of 1A domain of KRT6A, both are hotspots for pathogenic keratin mutations.

CONCLUSIONThe mutations Y465H and N171D of the KRT16A gene were detected in the pedigree and the sporadic case respectively. The Y465H mutation was a novel mutation, and the N171D mutation was reported recently.

Asian Continental Ancestry Group ; genetics ; Base Sequence ; Female ; Humans ; Keratin-6 ; genetics ; Male ; Molecular Sequence Data ; Mutation ; Pachyonychia Congenita ; genetics ; Pedigree