OBJECTIVE: To screen the population for acupuncture treatment of neck pain, using functional magnetic resonance imaging (fMRI) technology and based on machine learning algorithms. METHODS: Eighty patients with neck pain were recruited. Using FPX25 handheld pressure algometer, the tender points were detected in the areas with high-frequent onset of neck pain and high degree of acupoint sensitization. Acupuncture was delivered at 4 tender points with the lowest pain threshold, once every two days; and the treatment was given 3 times a week and for 2 consecutive weeks. The amplitude of low-frequency fluctuation (ALFF) of the brain before treatment was taken as a predictive feature to construct support vector machine (SVM), logistic regression (LR), and K-nearest neighbors (KNN) models to predict the responses of neck pain patients to acupuncture treatment. A longitudinal analysis of the ALFF features was performed before and after treatment to reveal the potential biological markers of the reactivity to the acupuncture therapy. RESULTS: The SVM model could successfully distinguish high responders (48 cases) and low responders (32 cases) to acupuncture treatment, and its accuracy rate reached 82.5%. Based on the SVM model, the ALFF values of 4 brain regions were identified as the consistent predictive features, including the right middle temporal gyrus, the right superior occipital gyrus, and the bilateral posterior cingulate gyrus. In the patients with high acupuncture response, the ALFF value in the left posterior cingulate gyrus decreased after treatment (P<0.05), whereas in the patients with low acupuncture response, the ALFF value in the right superior occipital gyrus increased after treatment (P<0.01). The longitudinal functional connectivity (FC) analysis found that compared with those before treatment, the high responders showed the enhanced FC after treatment between the left posterior cingulate gyrus and various regions, including the bilateral Crus1 of the cerebellum, the right insula, the bilateral angular gyrus, the left medial superior frontal gyrus, and the left middle cingulate gyrus (GRF: corrected, voxel level: P<0.05, mass level: P<0.05). In contrast, the low responders exhibited the enhanced FC between the left posterior cingulate gyrus and the left Crus2 of the cerebellum, the left middle temporal gyrus, the right posterior cingulate gyrus, and the left angular gyrus; besides, FC was reduced in low responders between the left posterior cingulate gyrus and the right supramarginal gyrus (GRF: corrected, voxel level: P<0.05, mass level: P<0.05). CONCLUSION This study validates the practicality of pre-treatment ALFF feature prediction for acupuncture efficacy on neck pain. The therapeutic effect of acupuncture on neck pain is potentially associated with its impact on the default mode network, and then, alter the pain perception and emotional regulation.
Humans ; Neck Pain/physiopathology* ; Acupuncture Therapy ; Female ; Male ; Adult ; Middle Aged ; Machine Learning ; Magnetic Resonance Imaging ; Young Adult ; Brain/physiopathology* ; Acupuncture Points ; Aged

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Objective: To understand current status and related factors of breakfast among primary and secondary school students in Zhejiang Province, so as to provide a scientific basis for improving breakfast habits of primary and secondary school students. Methods: During May to November of 2023, 33 326 students from grade four to six of primary schools and grade one to two of secondary schools were selected from 90 counties and cities in Zhejiang Province by using the stratified cluster random sampling method. General information and breakfast consumption were collected by questionnaire. Multivariate Logistic regression was used to analyze the related factors of breakfast. Results: About 81.29% of the primary and secondary school students reported regular breakfast consumption. The rate of regular breakfast consumption was higher on the school days (92.23%) than on the weekends (85.17%), and higher in primary school students (85.83%) compared to secondary school students (74.71%), with statistically significant differences ( χ 2=827.42, 655.03, P <0.01). About 49.19% of primary and secondary school students had their breakfast within 10 minutes or less, and 83.30% of primary and secondary school students had 3-5 food groups for breakfast. The proportions of students who consumed cereals and potatoes, milk, and eggs were respectively 18.76%, 28.85%, 14.63%. About 22.84%, 28.00 %, 32.60% and 32.23% of the students had no meat, soybeans, vegetables and fruits in their breakfast. The results of multivariate Logistic regression analysis showed that girls, rural area, secondary school, place of living (dormitory, others), migrant parent (one or both outside the hometown), late bedtime (22:00-22:59, 23:00 and later) and late wake up time (9:00 and later) on the weekends were positively correlated with no having breakfast every day ( OR=1.22, 1.40, 1.46, 1.20, 1.20, 1.34, 1.36, 1.41 , 3.51, 2.32, P <0.05). The time of physical activity per day (30-<60, 60-<90, 90-120, >120 min), bedtime (21:00-21:59, 22:00-22:59) and wake up time (6:00-6:59, 7:00-7:59) on school days were negatively correlated with no having breakfast every day ( OR=0.75, 0.64, 0.67, 0.64, 0.77, 0.82, 0.75, 0.67, P <0.05). Conclusions There is a considerable number of primary and secondary school students with irregular breakfast consumption, which are related to multiple factors. Therefore, it is necessary to strengthen nutrition education and improve the behavior of breakfast for primary and secondary school students.

Objective To investigate the protective effect of PF-562271,a FAK inhibitor,against aging platelet-induced injury in human umbilical vein endothelial cells(HUVECs).Methods Cultured HUVECs were treated with vehicle,lipopolysaccharide(LPS),LPS+aging platelets,or LPS+aging platelets+PF-562271.The changes in protein expressions of FAK,pFAK and PECAM-1 in the treated cells were detected using Western blotting and immunofluorescence assay,and the level of reactive oxygen species(ROS)was detected with flow cytometry.The changes of barrier function of the cells were assessed with cell permeability test and transendothelial cell resistance test.RT-qPCR was used to analyze mRNA expressions of inflammatory factors,and pro-inflammatory cytokine levels in the culture supernatants was determined with enzyme-linked immunosorbent assay.Immunofluorescence assay was used to examine the effect of the ROS inhibitor vitamin C on PECAM-1 expression in the cells with different treatments.Results Treatment of HUVECs with LPS and aging platelets significantly increased cellular protein expressions of FAK,pFAK and PECAM-1,which were effectively lowered by addition of PF-562271(P<0.05).LPS and aged platelets obviously enhanced ROS production in the cells,which was inhibited by the addition of PF-562271(P<0.001).PF-562271 significantly alleviated the damage of endothelial cell barrier function of the cells caused by LPS and aging platelets(P<0.01).The expressions of TNF-α,IL-6 and IL-8 in HUVECs increased significantly after exposure to LPS and aging platelets,and were obviously lowered after treatment with PF-562271(P<0.05).Treatment with vitamin C significantly decreased the expression of PECAM-1 protein in the cells(P<0.01).Conclusion The FAK inhibitor PF-562271 alleviates endothelial cell damage induced by LPS and aging platelets by lowering cellular oxidative stress levels and reducing inflammatory responses.

Objective To investigate the protective effect of PF-562271,a FAK inhibitor,against aging platelet-induced injury in human umbilical vein endothelial cells(HUVECs).Methods Cultured HUVECs were treated with vehicle,lipopolysaccharide(LPS),LPS+aging platelets,or LPS+aging platelets+PF-562271.The changes in protein expressions of FAK,pFAK and PECAM-1 in the treated cells were detected using Western blotting and immunofluorescence assay,and the level of reactive oxygen species(ROS)was detected with flow cytometry.The changes of barrier function of the cells were assessed with cell permeability test and transendothelial cell resistance test.RT-qPCR was used to analyze mRNA expressions of inflammatory factors,and pro-inflammatory cytokine levels in the culture supernatants was determined with enzyme-linked immunosorbent assay.Immunofluorescence assay was used to examine the effect of the ROS inhibitor vitamin C on PECAM-1 expression in the cells with different treatments.Results Treatment of HUVECs with LPS and aging platelets significantly increased cellular protein expressions of FAK,pFAK and PECAM-1,which were effectively lowered by addition of PF-562271(P<0.05).LPS and aged platelets obviously enhanced ROS production in the cells,which was inhibited by the addition of PF-562271(P<0.001).PF-562271 significantly alleviated the damage of endothelial cell barrier function of the cells caused by LPS and aging platelets(P<0.01).The expressions of TNF-α,IL-6 and IL-8 in HUVECs increased significantly after exposure to LPS and aging platelets,and were obviously lowered after treatment with PF-562271(P<0.05).Treatment with vitamin C significantly decreased the expression of PECAM-1 protein in the cells(P<0.01).Conclusion The FAK inhibitor PF-562271 alleviates endothelial cell damage induced by LPS and aging platelets by lowering cellular oxidative stress levels and reducing inflammatory responses.

Abstract: Approximately 2 billion people worldwide are infected with helminths and the resulting helminthiasis is a heavy health burden for developing countries. Parasitic helminths are a class of multicellular parasites, mainly including trematodes, tapeworms and nematodes, wtih complex life cycle involving multiple developmental stages and typically one or more hosts. Understanding the growth, development, pathogenesis and transmission of these parasites at the molecular level is of great significance for the diagnosis and treatment of helminthiasis. Genetic manipulations, which alter the expression level of target genes, have greatly promoted the biomedical research. In recent years, with the release of genomic data of worms, genetic manipulation techniques, such as RNA interference and clustered regularly interspaced short palindromic repeats (CRISPR) gene editing, have been increasingly applied in the studies of parasitic helminths. This article reviews the progress of genetic manipulations in important medical worms, as well as the methods of genetic manipulations, which would be expected to inspire the future functional study in parasitic helminths.

Multiple myeloma (MM) is still an incurable hematologic malignancy, which is eagerly to the discovery of novel therapeutic targets and methods. N-acetyltransferase 10 (NAT10) is the first reported regulator of mRNA acetylation that is activated in many cancers. However, the function of NAT10 in MM remains unclear. We found significant upregulation of NAT10 in MM patients compared to normal plasma cells, which was also highly correlated with MM poor outcome. Further enforced NAT10 expression promoted MM growth in vitro and in vivo, while knockdown of NAT10 reversed those effects. The correlation analysis of acetylated RNA immunoprecipitation sequencing (acRIP-seq) and ribosome profiling sequencing (Ribo-seq) combined with RIP-PCR tests identified centrosomal protein 170 (CEP170) as an important downstream target of NAT10. Interfering CEP170 expression in NAT10-OE cells attenuated the acceleration of cellular growth caused by elevated NAT10. Moreover, CEP170 overexpression promoted cellular proliferation and chromosomal instability (CIN) in MM. Intriguingly, remodelin, a selective NAT10 inhibitor, suppressed MM cellular growth, induced cellular apoptosis in vitro and prolonged the survival of 5TMM3VT mice in vivo. Collectively, our data indicate that NAT10 acetylates CEP1 70 mRNA to enhance CEP170 translation efficiency, which suggests that NAT10 may serve as a promising therapeutic target in MM.

Objective:In general, patients with seropositive rheumatoid arthritis (RA) are considered to show an aggressive disease course. However, the relationship between the two subgroups in disease severity is controversial. Our study is aimed to compare the clinical characteristics and prognosis of double-seropositive and seronegative RA in China through a real-world large scale study.Methods:RA patients who met the 1987 American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European Anti-Rheumatism Alliance RA classification criteria, and who attended the 10 hospitals across the country from September 2015 to January 2020, were enrolled. According to the serological status, patients were divided into 4 subgroups [rheumatoid factor (RF)(-) anti-cyclic citrullinated peptide (CCP) antibody (-), RF(+), RF(+) anti-CCP antibody(+), anti-CCP antibody(+)] and compared the disease characteristics and treatment response. One-way analysis of variance was used for measurement data that conformed to normal distribution, Kruskal-Wallis H test was used for measurement data that did not conform to normal distribution; paired t test was used for comparison before and after treatment within the group if the data was normally distributed else paired rank sum test was used; χ2 test was used for count data. Results:① A total of 2 461 patients were included, including 1 813 RF(+) anti-CCP antibody(+) patients (73.67%), 129 RF(+) patients (5.24%), 245 RF(-) anti-CCP antibody(-) patients (9.96%), 74 anti-CCP antibody(+) patients (11.13%). ② Regardless of the CCP status, RF(+) patients had an early age of onset [RF(-) anti-CCP antibody(-) (51±14) years old, anti-CCP antibody(+) (50±15) years old, RF(+) anti-CCP antibody(+) (48±14) years old, RF(+)(48±13) years old, F=3.003, P=0.029], longer disease duration [RF(-) anti-CCP antibody(-) 50 (20, 126) months, anti-CCP antibody(+) 60(24, 150) months, RF(+) anti-CCP antibody(+) 89(35, 179) months, RF(+) 83(25, 160) months, H=22.001, P<0.01], more joint swelling counts (SJC) [RF(-) anti-CCP antibody(-) 2(0, 6), Anti-CCP antibody(+) 2(0, 5), RF(+) anti-CCP antibody(+) 2(0, 7), RF(+) 2(0, 6), H=8.939, P=0.03] and tender joint counts (TJC) [RF(-) anti-CCP antibody(-) 3(0, 8), anti-CCP antibody(+) 2(0, 6), RF(+) anti-CCP antibody(+) 3(1, 9), RF(+) 2(0, 8), H=11.341, P=0.01] and the morning stiff time was longer [RF(-) anti-CCP antibody(-) 30(0, 60) min, anti-CCP antibody(+) 20(0, 60) min, RF(+) anti-CCP antibody(+) 30(10, 60) min, RF(+) 30(10, 60) min, H=13.32, P<0.01]; ESR [RF(-) anti-CCP antibody(-) 17(9, 38) mm/1 h, anti-CCP antibody(+) 20(10, 35) mm/1 h, RF(+) anti-CCP antibody(+) 26(14, 45) mm/1 h, RF(+) 28(14, 50) mm/1 h, H=37.084, P<0.01] and CRP [RF(-) anti-CCP antibody(-) 2.3 (0.8, 15.9) mm/L, Anti-CCP antibody(+) 2.7(0.7, 12.1) mm/L, RF(+) anti-CCP antibody(+) 5.2(1.3, 17.2) mm/L, RF (+) 5.2(0.9, 16.2) mm/L, H=22.141, P<0.01] of the RF(+)patients were significantly higher than RF(-) patients, and RF(+) patients had higher disease severity(DAS28-ESR) [RF(-) anti-CCP antibody(-) (4.0±1.8), anti-CCP antibody(+) (3.8±1.6), RF(+) anti-CCP antibody(+) (4.3±1.8), RF(+) (4.1±1.7), F=7.269, P<0.01]. ③ The RF(+) anti-CCP antibody(+) patients were divided into 4 subgroups, and it was found that RF-H anti-CCP antibody-L patients had higher disease severity [RF-H anti-CCP antibody-H 4.3(2.9, 5.6), RF-L anti-CCP antibody-L 4.5(3.0, 5.7), RF-H anti-CCP antibody-L 4.9(3.1, 6.2), RF-L anti-CCP antibody-H 2.8(1.8, 3.9), H=20.374, P<0.01]. ④ After 3-month follow up, the clinical characteristics of the four groups were improved, but there was no significant difference in the improvement of the four groups, indicating that the RF and anti-CCP antibody status did not affect the remission within 3 months. Conclusion:Among RA patients, the disease activity of RA patients is closely related to RF and the RF(+) patients have more severe disease than RF(-) patients. Patients with higher RF titer also have more severe disease than that of patients with low RF titer. After 3 months of medication treatment, the antibody status does not affect the disease remission rate.

Objective: To investigate the association between dietary selenium intake and hypertension among Zhejiang residents . Methods: By multistage stratified random sampling method,four urban sites and two rural sites out of Zhejiang Province,four communities or villages out of each site,then 20 households out of each community or village were selected,and all the family members of the selected households were recruited as participants. The questionnaire of Chinese Health and Nutrition Survey was used to collect information about socio-demographic characteristics and dietary selenium intake. The blood pressure,blood lipid and other data were collected via physical examination. A multivariate logistic regression model was used to analyze the relationship between dietary selenium intake and hypertension . Results: A total of 1 222 participants with complete dietary selenium intake data were included for analysis. The number（%）of participants with selenium intake higher than the level of estimated average requirement（EAR）,between the levels of EAR and recommanded nutrient intake （RNI）,between the levels of RNI and upper intake（UI）and higher than the level of UI were 729 （59.66%）,151（12.36%）,341（27.91%）and 1（0.01%）,respectively. There were 283 （30.53%）patients with hypertension out of 927 participants examined. The mean amount of selenium intake in patients with hypertention was（43.06±20.96）μg/d,which was significantly lower than（51.56±30.06） μg/d in non-hypertention participants（P<0.05）. After adjusting for age,body mass index,total cholesterol,triglyceride and diabetes mellitus in the multivariate logistic regression model,dietary selenium intake significantly reduced the risk of hypertension（OR=0.985,95%CI：0.978-0.993） . Conclusion About 60% of residents in Zhejiang Province had lower dietary selenium intake than estimated average requirement. Higher selenium intake was associated with lower risk of hypertension.

Objective To evaluate the effect of recombinant human annexin A5 on the expression of phosphorylated protein kinase C alpha (p-PKCα) and p120-catenin during endotoxin-induced damage to cardiomyocytes.Methods H9c2 cells cultured in vitro were randomly divided into 3 groups (n=18 each) using a random number table:control group (group C),endotoxin group (group L),and recombinant human annexin A5 group (group A).Recombinant human annexin A5 (final concentration 5 ng/ml) was added,and the cells were incubated for 2 h in group A,and then lipopolysaccharide (final concentration 1 μg/ml) was added,and the cells were incubated for 4 h in L and A groups.At 4 h of incubation,cell apoptosis was detected using the cell apoptosis detection kit,the intercellular space was measured using the confocal microscopy,and the expression of p-PKCα and p120-catenin was determined by Western blot.The apoptosis rate was calculated.Results Compared with group C,the apoptosis rate was significantly increased,the intercellular space was significantly widened,the expression of p120-catenin was significantly down-regulated,and the expression of p-PKCα was significantly up-regulated in group L (P＜0.05).Compared with group L,the apoptosis rate and intercellular space were significantly decreased,the expression of p120-catenin was significantly up-regulated,and the expression of p-PKCα was significantly down-regulated in group A (P＜0.05).Conclusion Recombinant human annexin A5 can inhibit phosphorylation of PKCα and up-regulate the expression of p120-catenin,thus attenuating endotoxin-induced damage to cardiomyocytes.