The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Objective:To explore the value of conventional magnetic resonance imaging (MRI), diffusion weighted imaging (DWI), diffusion kurtosis imaging (DKI) sequence and pathological examination in predicting the efficacy of neoadjuvant chemotherapy (NAC) in advanced breast cancer.Methods:The clinical data of 65 cases of advanced breast cancer with NAC confirmed by pathology in the Affiliated Hospital of Jining Medical University from March 2022 to May 2023 were retrospectively analyzed, including 20 cases in the pathological complete remission (pCR) group and 45 cases in the non pCR group; All patients underwent routine MRI, DWI, DKI examinations and pathological analysis. The clinical pathological data, routine MRI features, apparent diffusion coefficient (ADC) values, mean kurtosis coefficient (MK), and mean diffusion coefficient (MD) between the two groups were analyzed; We compared the differences in various parameters between two groups and plotted receiver operating characteristic (ROC) curves to compare their diagnostic efficacy of NAC in breast cancer.Results:There were significant differences in molecular typing, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2) and Ki-67 between pCR group and non pCR group (all P<0.05). In pCR group, Her-2 overexpression type and triple negative breast cancer (TNBC) type breast cancer were more common. ER and PR were mostly negative, Her-2 was mostly positive, and Ki 67 was mainly positive. The difference in tumor T2WI signal between the pCR group and the non pCR group was statistically significant ( P<0.05), with the pCR group showing mostly moderate/low T2WI signal. The ADC and MD values of the pCR group were lower than those of the non pCR group, while the MK value of the pCR group was higher than that of the non pCR group, and the differences were statistically significant (all P<0.001). The area under the ROC curve (AUC) for predicting the efficacy of NAC using a clinical pathological model was 0.829, which was higher than the AUC of molecular subtypes, ER, PR, Her-2, and Ki-67 ( Z=3.008, 2.697, 2.815, 2.131, 2.376, all P<0.05); The AUC of the DKI+ DWI predicting the efficacy of NAC was 0.934, which was higher than that of the DWI single sequence model, and the difference in type was statistically significant ( Z=2.396, P=0.017). The diagnostic efficacy of the DKI+ DWI model was higher than that of the single parameter ADC, MD, and MK, and the differences were statistically significant ( Z=2.396, 2.219, 2.161, all P<0.05); The AUC of the combined imaging and pathology model was 0.983, and its diagnostic efficacy was higher than that of the conventional MRI feature model, pathology model, DWI model, and DKI model, with statistically significant differences ( Z=5.877, 2.961, 3.240, 2.264, all P<0.05). Conclusions:The results of pathology, conventional MRI, DWI and DKI parameters of pCR and non pCR breast cancer patients are significantly different, and the combined model is better than the single model in predicting the efficacy of NAC.

Objective:To analyze the endoscopic characteristics of early gastric cancer and precancerous lesions after Helicobacter pylori ( H. pylori) eradication. Methods:From May 2019 to June 2022, at Shanghai Sixth People′s Hospital affiliated to Shanghai Jiaotong University School of Medicine, the medical data of patients diagnosed with differentiated early gastric cancer and precancerous lesions were collected. A total of 93 patients with early gastric cancer and precancerous lesions who had previous history of H. pylori infection and had undergone standardized eradication treatment were selected, and their endoscopic characteristics were retrospectively analyzed. Independent sample t-test, chi-square test, and Fisher′s exact test were used for statistical analysis. Results:Among 93 patients with early gastric cancer and precancerous lesions after H. pylori eradication, there were 56 males and 37 females, with an average age of (66.9±8.2) years old. The time after H. pylori eradication was 3.4 years (range 1.0 to 7.0 years). A total of 109 early gastric cancer and precancerous lesions were found, including 79 patients with single lesion and 14 patients with multiple lesions (30 lesions). There were 60 cases with 73 lesions in the early gastric cancer group and 33 cases with 36 lesions in the precancerous group. Among 93 patients, 89 cases (95.7%) were diagnosed with atrophy level above C-2 according to Kimura-Takemoto classification under endoscopy. The long diameter of 109 lesions was (1.38±0.70) cm and the short diameter was (1.04±0.53) cm. A total of 80 lesions (73.4%) were located in the lower 1/3 part of the stomach, and 53 lesions (48.6%) were located in the lesser curvature. A total of 106 lesions (97.2%) were superficial type (0-Ⅱ) under the endoscopy. The long diameter and short diameter in the early gastric cancer group after H. pylori eradication were both greater than those in the precancerous lesion group ((1.54±0.78) cm vs. (1.06±0.35) cm, (1.16±0.58) cm vs. (0.78±0.33) cm), and the differences were statistically significant ( t=3.53 and 3.73, both P<0.001). There was statistically significant difference in the morphological types between early gastric cancer group after H. pylori eradication and precancerous lesion group ( χ2=11.01, P=0.012). The main morphological type of early gastric cancer after H. pylori eradication was superficial depression type (0-Ⅱc), accounting for 45.2% (33/73), while the precancerous lesions were mainly superficial protruded and flat type, both accounting for 38.9% (14/36). Conclusions:After H. pylori eradication, the endoscopic atrophy range of early gastric cancer and precancerous lesions is mostly above C-2. And the lesions are mostly located in the middle and lower 1/3 part of the stomach, long diameter of lesions <20 mm. The main morphological type is superficial type, especially superficial depression type.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) positively affect the initial control of non-small cell lung cancer (NSCLC). Rapidly acquired resistance to EGFR-TKIs is a major hurdle in successful treatment. However, the mechanisms that control the resistance of EGFR-TKIs remain largely unknown. RNA structures have widespread and crucial functions in many biological regulations; however, the functions of RNA structures in regulating cancer drug resistance remain unclear. Here, the psoralen analysis of RNA interactions and structures (PARIS) method is used to establish the higher-order RNA structure maps of EGFR-TKIs-resistant and -sensitive cells of NSCLC. Our results show that RNA structural regions are enriched in untranslated regions (UTRs) and correlate with translation efficiency (TE). Moreover, yrdC N⁶-threonylcarbamoyltransferase domain containing (YRDC) promotes resistance to EGFR-TKIs. RNA structure formation in YRDC 3' UTR suppresses embryonic lethal abnormal vision-like 1 (ELAVL1) binding, leading to EGFR-TKI sensitivity by impairing YRDC translation. A potential therapeutic strategy for cancer treatment is provided using antisense oligonucleotide (ASO) to perturb the interaction between RNA and protein. Our study reveals an unprecedented mechanism through which the RNA structure switch modulates EGFR-TKI resistance by controlling YRDC mRNA translation in an ELAVL1-dependent manner.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; ErbB Receptors/metabolism* ; GTP-Binding Proteins/therapeutic use* ; Lung Neoplasms/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; RNA ; RNA-Binding Proteins/genetics* ; Tyrosine Kinase Inhibitors/therapeutic use*

Objective:To explore the prevalence of gout and related factors in community population, thereby provide evidence for comprehensive prevention and control of gout in community.Methods:A stratified multi-stage cluster sampling was used to survey the permanent residents of 20 to 75 years old in the 3 selected streets (towns), univariate analysis was performed using logistic regression by SPSS statistical software.Results:The prevalences of hyperuricemia and gout were 9.82% and 5.75% respectively(male 18.88% and 7.94%, female 3.79% and 4.29%)in Jiading Shanghai. The positive rate of family history was 17.13%, and the relationship between family history and gout was significant( OR=3.140, 95% CI 2.365-4.169, P<0.01). Age( OR=1.034, 95% CI 1.021-1.047), body mass index ( OR=1.102, 95% CI 1.074-1.131), waist-hip ratio ( OR=4.876, 95% CI 1.153-20.622), sleep quality ( OR=1.310, 95% CI 1.159-1.480), other animal meat ( OR=1.117, 95% CI 1.007-1.240), fresh water fish ( OR=1.138, 95% CI 1.005-1.288), and processed meat ( OR=1.145, 95% CI 1.033-1.270) were closely related to gout ( P<0.05 or P<0.01). Sex, alcohol drinking, marine fish, and soybean milk/soymilk were related to gout ( P<0.05 or P<0.01), but showed a protective effect ( OR<1.000). Conclusion:Reducing uric acid production through less consumption of purine-rich food such as animal meat as well as processed meat and weight control would be helpful in preventing gout.

Objective:To evaluate the intrauterine transmission of syphilis in Nantong City, Jiangsu Province from 2012 to 2019, after the introduction of a nationwide policy for preventing intrauterine transmission of syphilis in China in 2011.Methods:This study enrolled all live birth deliveries ( n=455 561) in Nantong from January 2012 to December 2019. The screening, infection rates, anti-syphilis treatment, intrauterine transmission of syphilis, and outcomes of infants with congenital syphilis were retrospectively analyzed using χ 2 test for trend, adjusted χ 2 test, or Fisher's exact test. Results:Except for three women, the remaining 455 558 subjects were all screened for syphilis antibody with a total screening rate of nearly 100%, among which prenatal screening accounted for 96.4% (439 125/455 561) and intrapartum screening for 3.6% (16 433/455 561). In total, 796 (0.17%) women were diagnosed with syphilis during pregnancy, and the prevalence increased from 0.13% (85/64 229) in 2012 to 0.24% (110/45 517) in 2019 (χ 2trend=48.985, P<0.001). The prevalence among women underwent intrapartum screening was significantly higher than those underwent prenatal screening [0.50% (82/16 433) vs 0.16% (714/439 125), χ 2=102.769, P<0.001]. Out of the women with syphilis, 716 (89.9%) received anti-syphilis therapy with 695 cases using penicillin, 16 cases using ceftriaxone and five using erythromycin/azithromycin, while the remaining 80 (10.1%) did not. Intrauterine transmission of syphilis occurred in 14 infants with a transmission rate of 1.8% (14/796). The reported rate of congenital syphilis in all live infants was 0.03‰ (14/460 552). The intrauterine transmission rate in women receiving treatment during pregnancy was significantly lower than that in the untreated women [0.4% (3/716) vs 13.8% (11/80), χ2=66.499, P<0.001]. For the untreated women, the intrauterine transmission rate increased with the rising titers of non-specific syphilis antibody ( χ2trend=5.338, P=0.021). Among infants with congenital syphilis, no obvious adverse outcomes occurred in three infants born to treated mothers, whereas the rates of preterm birth and neonatal death were 7/11 and 2/11 in those born to untreated mothers. Conclusions:Since the implementation of the policy against intrauterine transmission of syphilis, the reported rate of congenital syphilis is 3/100 000 live-birth in Nantong City, reaching the national target of below 15/100 000. Screening and treatment in the first trimester are critical for preventing intrauterine transmission of syphilis. Increased prenatal syphilis screening rate can help further reduction of the intrauterine transmission of syphilis.

Objective:To explore the effect of aerobic exercise on the food intake of obesity rats and obesity resistant rats and some mechanisms Method:The four years old Sprague-Dawley rats were randomly divided into standard chow group (C) and high-fat diet group.After 10 weeks feeding,the obese group (OB group) and obesity resistant group (OR group) induced by high-fat diet were screened out.Then all the rats in OB group and OR group were respectively and randomly divided into exercise rats (OB-Sw group,OR-Sw group) and non-exercise rats (OB-Sed group,OR-Sed group).Aerobic swimming exercise for the exercise rats was defined as 60％ of individual exhaustion exercise intensity,45 minutes per day,5 times per week.Meanwhile,the body weight and food intake of the exercise and non-exercise rats were monitored every week.After 8 weeks intervention,the serum and gastric tissue of rats were obtained,and then the TG,TC,LDL-c,HDL-c in serum and the expression of ghrelin in gastric tissue were detected.Result:Ten weeks later,the body weight of the rats with high-fat diet showed a significant difference compared with the rats with standard chow group (P ＜ 0.05).The content of LDL in OB-Sed group was significantly higher than that in C group (P＜0.05).After 8 weeks aerobic exercise,for the food intake,OB-Sed group was higher than OB-Sw group and OR-Sed group was higher than OB-Sw group.The expression of ghrelin in gastric tissue in OB-Sed group and OR-Sed group was higher than that in OB-Sw group,OB-Sw group and C group.Conclusion:Exercise might reduce the food intake of obesity rats and obesity resistant rats by reducing the expression of ghrelin in stomach.

Objective To evaluate the clinical efficacy of acupuncture plus acupoint application in treating irritable bowel syndrome with diarrhea (IBS-D).Method Sixty patients were randomized into two groups, 30 cases in each group. The acupuncture group was intervened by acupuncture at Neiguan (PC6), Zhongwan (CV12), and Zusanli (ST36), etc, plus application withBai Jie Zi(Semen Brassicae) powder at Qihai (CV6), Guanyuan (CV4), and Tianshu (ST25), etc; the medication group was prescribed with oral administration of Trimebutine maleate capsules (0.2 g each dose, 3 times a day). Four-week treatment was taken as a course. The symptoms score and quality of life (QOL) scale were evaluated prior to and after the treatment.Result The clinical symptoms were significantly improved in the acupuncture group, and the total effective rate was89.3%, significantly higher than 63.0% in the medication group (P<0.05). After 4-week treatment, the clinical symptoms scores of the two groups were analyzed by rank-sum test (Z=-19.627,P=0.000<0.05), revealing a significant difference between the two groups and indicating that the improvements of clinical symptoms in the acupuncture group were more significant than those in the medication group. After 4-week treatment, the general QOL scores of the two groups were examined by rank-sum test (Z=-10.039, P=0.000<0.05), revealing a significant difference between the two groups and indicating that the improvement of QOL in the acupuncture group was superior to that in the medication group.Conclusion Acupuncture plus acupoint application can obviously mitigateabdominal pain and discomfort.

Aim To investigate the anti-tumor effects of FS-108 an Hsp90 inhibitor, on oncogene addicted EBC-1 and A375 cells. Methods SRB assay was performed to investigate cell proliferation. Immunoblot was conducted to investigate the specific proteins. FACS was conducted to test cell cycle distribution and apoptosis. Transwell assay was conducted to investigate cell motility. Results FS-108 significantly suppressed cell proliferation of EBC-1 and A375 cancer cells with IC50 at 25. 53 nmol · L-1 and 30. 02 nmol · L-1 re-spectively. FS-108 treatment triggered the degradation of key client proteins such as c-Met and B-Raf and thereby reduced their downstream AKT and ERK signa-ling pathways. The FACS analysis results demonstrated that FS-108 treatment induced G2/M phase arrest and apoptosis significantly. Furthermore, FS-108 inhibited the migration of EBC-1 and A375 cells. Conclusion As a potent Hsp90 inhibitor, FS-108 can inhibit onco-gene addicted cancer cells proliferation through induc-tion of G2/M phase arrest and apoptosis.