Background and purpose:Colorectal cancer(CRC)is one of the major malignant tumors threatening human health worldwide,with long-term high incidence and mortality rate.Potassium channel modulatory factor 1(KCMF1)is a member of the E3 ubiquitin ligase family.It binds to target proteins through the RING domain and participates in the regulation of a variety of biological processes in vivo.However,the function of KCMF1 in CRC remains unclear.This study aimed to investigate the expression level of E3 ubiquitin ligase KCMF1 in colorectal tumor,and to explore the effects of KCMF1 on the proliferation of CRC cells and its underlying molecular mechanism.Methods:The The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases were used to analyze the expression level of KCMF1 in CRC tissues and adjacent tissues and the association between the KCMF1 expression and the prognosis of CRC patients.Furthermore,immunohistochemical staining was performed to detect the protein level of KCMF1 in 90 paired human CRC tissues and adjacent non-tumor tissues.Lentiviral shRNA delivery system was employed to specifically target the KCMF1 gene(shKCMF1)in HCT116 and HCT15 CRC cell lines.The effects of KCMF1 knockdown on cell proliferation,apoptosis and cell cycle distribution were assessed by methyl thiazoyl terazolium(MTT)assay,colony formation assay,Western blot and flow cytometry.Changes in the transcriptional profile in HCT116 cells upon KCMF1 knockdown were identified by RNA sequencing(RNA-Seq),and the affected signaling pathways were evaluated by bioinformatics analysis.Real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR),Western blot,luciferase reporter assay and cell immunofluorescence assay were utilized to validate the alteration of the affected signaling pathway.Results:The TCGA and GTEx databases and IHC results showed that the mRNA and protein expression levels of KCMF1 in CRC tissues were significantly upregulated compared with adjacent tissues(P＜0.01).KCMF1 expression level was negatively correlated with the survival time of patients with CRC(P＜0.01),and was positively associated with CRC clinical stage(P＜0.05).Compared with control cells,KCMF1 knockdown significantly inhibited the proliferation of HCT116 and HCT15 cells(P＜0.001),induced cell apoptosis(P＜0.001),and led to cell cycle arrest in G1 phase(P＜0.01).RNA-Seq analysis showed that KCMF1 was involved in the regulation of several signaling pathways,including nuclear factor-κB(NF-κB)signaling pathway.KCMF1 knockdown reduced the transcription levels of the target genes of NF-κB signaling pathway,including BCL-XL,XIAP and CIAP(P＜0.05),and suppressed the expression of phosphorylated p65 and nuclear translocation of p65(P＜0.01).Meanwhile,the activity of NF-κB reporter was reduced in tumor cells upon KCMF1 knockdown(P＜0.01).Conclusion:The expression of KCMF1 is significantly upregulated in human CRC tissues and positively associated with advanced clinical stage and poor prognosis.KCMF1 may promote the proliferation of CRC cells by activating the NF-κB signaling pathway.KCMF1 may be a potential new therapeutic target for CRC.

Objective:To explore the standardization of totally implantable venous power port of nursing process in CT enhancement and application effect of contrast medium injection, so as to provide a safer and more efficient way for contrast medium injection in CT enhanced examination for patients with malignant tumors.Methods:A non-randomized prospective study was conducted, 358 patients with malignant tumors were selected in Sun Yat-sen Memorial Hospital, Sun Yat-sen University who underwent CT enhanced examination from August 1, 2022 to July 31, 2023, 179 patients who had been implanted totally implantable venous power port were selected as the experimental group, and the standardized nursing procedure was given. The other 179 patients were the control group, using radiology routine high-pressure intravenous indwelling needle as the contrast medium access, with routine peripheral venous nursing process. The incidence of contrast medium extravasation during CT enhanced examination was observed and compared between the two groups.Results:All the patients were included. There were 85 males and 94 females, aged (55.50±11.72) years old in the control group. There were 83 males and 96 females, aged (54.50±12.24) years old in the experimental group. The incidence of contrast medium extravasation was 0 in the experimental group and 3.35%(6/179) in the control group. The difference between the two groups was statistically significant (Fisher exact probability, P<0.05). Conclusions:The application of standardized nursing procedure of totally implantable venous power port to the injection of contrast medium in CT enhanced examination of malignant tumor patients, can significantly reduce the incidence of contrast medium extravasation.

Objective To analyze the medication rules of Professor LAO Shaoxian in the treatment of gastric stuffiness based on syndrome differentiation.Methods The effective prescriptions for patients with gastric stuffiness treated by Professor LAO Shaoxian from March 2017 to March 2022 were collected,and the general information,chief complaints,diagnosis,syndrome differentiation and prescriptions of patients were extracted.Excel software and the ancient and modern medical records cloud platform(V 2.3.7)were used to construct the prescription database.Data mining function was used to carry out analysis of the syndrome type of prescription,analysis of the frequency and property of Chinese herbs,as well as association rule analysis and cluster analysis.Results A total of 272 prescriptions were included,involving 164 kinds of medicinal herbs.The main traditional Chinese medicine(TCM)syndrome types are damp-heat syndrome and qi stagnation syndrome.The frequency of 25 herbs was more than or equal to 30 times.The representative herbs is Pinellinae Rhizoma Praeparatum,Glycyrrhizae Radix et Rhizoma,Citri Reticulatae Pericarpium,Perillae Caulis and Aucklandiae Radix.The medicinal properties are mainly warm and flat.The medicinal flavors are spicy,bitter and sweet.The drug meridians mainly included the spleen,stomach and lung meridians,followed by the liver meridian.There were 23 core drug pairs obtained by association rules,such as"Aucklandiae Radix-Perillae Caulis","Citri Reticulatae Pericarpium-Perillae Caulis",and"Pinellinae Rhizoma Praeparatum-Citri Reticulatae Pericarpium".Clustering analysis of drugs can be divided into three combinations,which have the effects of regulating qi and relieving distension,resolving dampness,and clearing heat and detoxifying.Conclusion The core prescription of Professor LAO Shaoxian in the treatment of gastric stuffiness is Aucklandiae Radix,Perillae Caulis,Citri Reticulatae Pericarpium,Pinellinae Rhizoma Praeparatum,Glycyrrhizae Radix et Rhizoma,Kaki Calyx,Aurantii Fructus Immaturus and Arecae Pericarpium.It focuses on regulating qi movement of middle jiao and treating spleen and stomach simultaneously.The main therapeutic method is regulating qi and relieving distension.At the same time,attention should be paid to the application of dampness-dispelling and stagnation-removing,heat-clearing and detoxifying drugs.The clinical therapy of Professor LAO Shaoxian on gastric stuffiness is significant,which can be used as a reference for diagnosis and treatment.

Purpose: Erectile dysfunction (ED) is a common postoperative complication of pelvic surgery for which there is currently no effective treatment. This study investigated the therapeutic effects and potential mechanisms of adipose derived mesenchymal stem cells-derived mitochondria (ADSCs-mito) transplantation in a rat model of bilateral cavernous nerve injury (CNI) ED. Materials and Methods: We isolated mitochondria from ADSCs and tested their quality. In vivo, twenty male Sprague Dawley rats were randomly divided into four groups: sham operation group and CNI groups that received intracavernous injection of either phosphate buffer solution, ADSCs-mito or ADSCs. Two weeks after therapy, the erectile function of the rats was evaluated and the penile tissues were harvested for histologic analysis and western blotting. In vitro, the apoptosis rate, reactive oxygen species (ROS), mitochondria derived active oxygen (mtROS) and adenosine triphosphate (ATP) levels were detected in corpus cavernosum smooth muscle cells (CCSMCs) after the incubation with ADSCs-mito. In addition, intercellular mitochondrial transfer was visualized by co-culture of ADSCs and CCSMCs. Results: The ADSCs, ADSCs-mito and CCSMCs were isolated and identified successfully. ADSCs-mito transplantation notably restored the erectile function and smooth muscle content of CNI ED rats. Moreover, the levels of ROS, mtROS and cleaved-caspase 3 were reduced and the levels of superoxide dismutase and ATP were increased after ADSCs-mito transplantation. In CNI ED rats, the mitochondrial structure of cells in penile tissues was destroyed. ADSCs could transfer its own mitochondria to CCSMCs. Pre-treatment with ADSCs-mito could significantly decrease apoptosis rate, ROS levels and mtROS levels as well as restore the ATP level in CCSMCs. Conclusions ADSCs-mito transplantation significantly ameliorated ED induced by CNI, with similar potency to ADSCs treatment. The ADSCs-mito might exert their effects via anti-oxidative stress, anti-apoptosis and modulating energy metabolism of CCSMCs. Mitochondrial transplantation should be a promising therapeutic method for treating CNI ED in the future.

A 58-year-old male patient with angioimmunoblastic T-cell lymphoma developed a rash and skin tightness on the face, limbs, and trunk together with joint stiffness and dysfunction after 6 months of treatment with the programmed cell death protein-1 inhibitor camrelizumab. Laboratory tests revealed progressive eosinophilia over 6 months, with the eosinophil count increasing from 0.07×10 9/L to 3.3×10 9/L. Magnetic resonance imaging showed thickened skin of both forearms, while T 2-weighted imaging showed markedly increased signal intensity within the myofascia. Skin biopsy of the right forearm showed thickened and fibrosed fascia and infiltration of inflammatory cells, including lymphocytes, plasma cells, and eosinophils. The patient was diagnosed with immune checkpoint inhibitor (ICI)-induced eosinophilic fasciitis (EF). After beginning treatment with methylprednisolone (40 mg daily), methotrexate (10 mg/week), and baricitinib (4 mg daily), his symptoms of skin tightness and joint dysfunction significantly improved within 1 month, and his peripheral blood eosinophil count decreased to 0.17×10 9/L. ICI-induced EF is a rare immune-related adverse reaction. To date, only 20 cases have been reported in published foreign literature, and their clinical characteristics are summarized here. The time from ICI treatment to EF was 12 (8,15) months, and the main clinical manifestations included skin involvement ( n=19), joint dysfunction ( n=11), myalgia/muscle weakness ( n=9), and peripheral eosinophilia ( n=16). After treatment, the clinical symptoms of EF improved in 17 patients, and eosinophil counts returned to normal after 3 (1,8) months. EF is a dysfunctional adverse response to ICI therapy. Tumor patients undergoing immunotherapy should be monitored for symptoms of EF. Early treatment is essential for preventing complications.

Objective:To explore the facilitating and inhibitory factors influencing the behavior of young patients to share medical electronic word-of-mouth (eWOM) on internet platforms, so as to provide insights for the improvement of healthcare quality.Methods:In May 2022, 271 undergraduate students from universities in Zhejiang province were selected by convenient sampling to survey their motivations to share eWOM with a self-designed questionnaire. Multiple regression analysis was used to examine the impact of different motivational factors on the sharing intention of young patients.Results:Only 16 respondents (5.9%) had previously published medical eWOM. Egoistic motivation, altruistic motivation, medical experience, and comment habits were significant factors that promoted patients to share eWOM, with egoistic motivation ( β=0.212, P<0.001) having the greatest impact and comment habit ( β=0.139, P=0.003) having the least impact. Distrust, low self-efficacy and involvement, perceived reluctance, and perceived uselessness were significant factors inhibiting patients from publishing eWOM. Of them, distrust ( β=-0.161, P<0.001) and perceived reluctance ( β=-0.161, P=0.001) had the greatest impact, and low self-efficacy and involvement had the least impact ( β=-0.134, P=0.003). Conclusions:To enhance the positive attitude of young patients towards sharing eWOM, it is important to focus on their personal benefits and provide high-quality healthcare experiences. Building trust among patients in the platform is crucial, and efforts should be made to reduce operational barriers. Additionally, educating and raising awareness among young patients regarding the significance and influence of healthcare reviews is important.

Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N⁶-methyladenosine (m⁶A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m⁶A methylation. We then indicate that SRSF7 is a novel m⁶A regulator, which specifically facilitates the m⁶A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m⁶A methyltransferase. The two m⁶A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m⁶A and validates the presence and functional importance of temporal- and spatial-specific regulation of m⁶A mediated by RNA-binding proteins (RBPs).
Humans ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioblastoma/genetics* ; Methyltransferases/metabolism* ; RNA Splicing Factors/metabolism* ; RNA, Messenger/genetics* ; RNA-Binding Proteins/metabolism* ; Serine-Arginine Splicing Factors/metabolism* ; RNA Methylation/genetics*

Objective:To describe the baseline characteristics of the subjects enrolled in the China Quantitative CT (QCT) big data program in 2018—2019.Methods:Based on baseline data from the Chinese health big data project from January 2018 to December 2019 from the eligible enrolled population, measurements of bone mineral density (BMD) and visceral adipose tissue (VAT) were performed using Mindways′ QCT Pro Model 4 system. The baseline data of age, gender, regional distribution, height, weight, abdominal circumference, blood pressure, blood routine and blood biochemical tests were analyzed. And the single factor analysis of variance (ANOVA) was used to check the age related trend of BMD and VAT in both genders.Results:After screening the inclusion exclusion criteria and outliers of the main indicators, 86 113 people were enrolled in the project. The enrollment rate was 92.47%, including 35 431 (41.1%) women and 50 682 (58.9%) men, and the ratio of men to women was 1.43. The mean age was (50.3±12.7) years in all the subjects, and it was (50.2±12.8) years and (50.4±12.5) years in men and women, respectively, and there was no statistical difference between the two genders ( P>0.05). Total of 43 833 people were enrolled in east China, it was the largest group by region (50.90%), it was followed by central China (16 434 people, 19.08%), and the number of people enrolled in Northeast China was the lowest (2 914 people, 3.38%). The rate of completing of health information indicators related to the main outcome of the study were all above 70%, and there were significant differences between men and women (all P<0.05). The mean BMD was (139.33±46.76) mg/cm 3 in women, (135.90±36.48) mg/cm 3 in men, which showed a decreasing trend with age in both gender (both P<0.001); the mean intra-abdominal fat area was (116.39±56.23) cm 2 in women, (191.67±77.07) cm 2 in men, and there was an increasing trend with age in both men and women (both P<0.001). Conclusions:There are gender differences in BMD and VAT measured by QCT with different age tendency, and there are gender differences in health information index. Regional factors should also be taken into account for regional differences in the inclusion of data.

Objective:To investigate the normal reference values of spinal bone mineral density measured by quantitative computed tomography (QCT) and the differences of bone mineral density (BMD) in different regions of in Chinese adult males.Methods:Men who underwent low-dose CT lung scan for cancer screening in regions of Northeast, North, East, South, Central and Southwest of China from January 2018 to December 2019 were selected. And the lumbar vertebrae BMD values in the male subjects were measured by the QCT system (Mindways Software, Inc.). The mean BMD values and their decline rates were calculated at an age interval of 10 years, and the prevalence of osteoporosis was calculated according to the American College of Radiology spine QCT osteoporosis diagnostic criteria.Results:A total of 50 682 males with a mean age of (50.22±12.79) years (ranged 20 to 98 years) were included in this study. The peak BMD of (173.11±28.56) mg/cm 3 in the healthy Chinese adult male population appeared in the age group of 20 to 29 years and then declined with age. Before the age of 70 years, the BMD was relatively higher in males in South China, and it was lower in Central China and Southwest China, and it was intermediate in Northeast, North and East of China, with statistically significant differences. There was no significant differences in BMD in the males in the two age groups of 70 to 79 years and 80 and older among the regions in China. The overall decline rate of spinal BMD in Chinese males under QCT was about 46.92% over the lifetime, and it declined obviouslyin the 40-49 age group. The overall prevalence of osteoporosis in Chinese male population aged 50 years and above was approximately 11.42%, with the highest prevalence in Southwest China and Central China (14.72% and 13.87%, respectively) and the lowest in North China and South China (8.53% and 7.71%, respectively). Conclusions:A reference of lumbar spine BMD values for healthy males in China based on QCT is established. BMD values were highest in South China and Lowest in Central China.

Objective:To establish the normal reference value of lumbar bone mineral density (BMD) under quantitative CT (QCT) in Chinese healthy adult females and to explore the regional differences.Methods:Total of 35 431 healthy women who met the inclusion criteria of Chinese health quantitative CT big data program were selected in this study. The BMD of the central plane of L 1 and L 2 vertebrae was measured by Mindways′s QCT system, and the mean value was taken. One-way analysis of variance was used to compare the BMD differences of lumbar vertebrae in women of different ages and regions. The subjects were grouped by an age interval of 10 years, and the level of BMD in different regions of the same age group were compaired. Results:The peak BMD of Chinese healthy adult women appeared in the age group of 20-29 years (Northeast China(183.01±24.58) mg/cm 3, North China (188.93±24.80) mg/cm 3, East China (187.54±27.71) mg/cm 3, South China (186.22±33.72) mg/cm 3, Central China (176.33±24.91) mg/cm 3, Southwest China(182.25±28.00) mg/cm 3), and then it decreased with age. The level of BMD in different regions decreased with the age. Before the age of 70 years, BMD in Central and Southwest China was always at a low level((176.23±24.91) to (90.38±28.12) mg/cm 3, 182.25±28.00 to (88.55±25.68) mg/cm 3), lower than those in Northeast China ((183.01±24.58) to (99.69±27.85) mg/cm 3), North China ((188.93±24.80) to (95.89±26.12) mg/cm 3), East China ((187.54±27.71) to (95.65±27.86) mg/cm 3). After 70 years of age, BMD tended to be the same in different regions ( P>0.05). The BMD values in Central China and Southwest China were similar in the age group of 40-60 years ( P>0.05). The BMD values in the health adult femles in the age group of 60 years in different regions of Chinawere all lower than those of bone mass abnormality (all P<0.05). The detection rate of osteoporosis in females over 50 years was the highest in Southwest China (25.65%) and it was the lowest in North China (17.30%). Conclusions:This study establishes reference values of BMD under QCT in healthy Chinese women, which can be used as a reference basis for identifying women with low BMD who are at risk of osteoporosis. The BMD value is the lowest in Southwest China and the highest in South China.