Objective:To explore the interaction effects on brain activity between the smoking addiction and weight status by resting-state functional magnetic resonance imaging.Methods:Retrospective analysis of clinical data and resting-state functional magnetic resonance imaging data were analyzed from 99 recruited subjects from January 2019 to December 2021. All participants were divided into four groups: overweight smokers ( n=24), normal-weight smokers ( n=28), overweight non-smokers ( n=19), and normal weight non-smokers ( n=28). Calculate regional homogeneity (ReHo) to reflect the internal brain activity of the subjects. Two-way ANOVA was used to detect the interaction effects between smoking addiction and overweight on ReHo by SPM12 software, correcting for age, years of education and head motion. Results:The interaction effect between smoking addiction and overweight on ReHo was significant in right superior frontal gyrus(x, y, z=15, 9, 60)(GRF corrected, Pvoxel<0.005, Pcluster<0.05). The ReHo value in the right superior frontal gyrus of overweight smokers was significantly higher than that of normal weight smokers ( t=3.768, P<0.001, Bonferroni corrected). The ReHo values in the right superior frontal gyrus of overweight non-smokers were significantly lower than those of normal weight non-smokers ( t=-3.242, P=0.002, Bonferroni corrected). The ReHo values in the right superior frontal gyurs of normal-weight smokers were significantly lower than those of normal weight non-smokers( t=-3.540, P=0.001, Bonferroni corrected). The ReHo values in the right superior frontal gyrus of overweight smokers were significantly higher than those of overweight non-smokers ( t=3.392, P=0.002, Bonferroni corrected). Correlation analyses showed that the strengthen ReHo value in right superior frontal gyrus was positively associated with pack-year in smoking addicts( r=0.387, P=0.007, Bonferroni corrected). Conclusion:Smoking addiction and overweight have an antagonistic effect on brain activity in the right superior frontal gyrus, which may provide potential therapeutic targets for individuals with comorbidity of smoking addiction and overweight.

Objective:To determine the optimal irradiation energy and frequency for the establishment of melasma mouse model using simple ultraviolet irradiation, and to provide guidance on animal strains and irradiation protocols for the successful establishment of melasma model.Methods:Animal models of melasma were established using BALB/c female mice and C57BL/6JNifdc female mice. BALB/c female mice were divided into 4 groups using a simple randomization method: A, B, C and G, with 5 mice in each group. C57BL/6JNifdc female mice were divided into 4 groups: D, E, F and H, with 5 mice in each group. All mice were irradiated with 8.428 mW/cm 2 of ultraviolet light. The irradiation time was 15 s (single irradiation energy of 0.13 J/cm 2) in groups A and D, 15 min (single irradiation energy of 7.59 J/cm 2) in groups B and E, and 30 min (single irradiation energy of 15.17 J/cm 2) in groups C and F. Each cycle consisted of 5 consecutive days of irradiation followed by 2 days of cessation, totaling 4 cycles of irradiation. Groups G and H were not irradiated. At the end of irradiation, all mice were kept under normal conditions. One week later, 3 mice from each group were selected for HE, Masson-Fontana, Masson, and immunohistochemical staining. Quantitative analysis was performed to measure the thickness of the acanthocyte layer, melanin granules, collagen percentage, and interleukin-1 (IL-1) levels. The remaining mice were kept for an additional week, depilated and photographed to observe the changes in coloration. Data were analyzed using SPSS 27.0 software, measurement data that did not conform to normal distribution were represented by M( Q1, Q3) and comparisons between groups were made using the Kruskal-Wallis rank sum test. Results:During the entire irradiation process, no visible discoloration was observed in the BALB/c female mice in all groups. In contrast, varying sizes of discoloration appeared in the C57BL/6JNifdc female mice in groups D, E, and F after irradiation in the second week. However, by the third week, the discoloration in group D gradually disappeared, while the discoloration in group E was more obvious than before. At the same time, group F exhibited significant discoloration, with some mice exhibited signs of skin peeling, burning and breakage on their backs. After the 4th week of irradiation, no new discoloration was formed in group D. The discoloration was more obvious in group E, and most mice in group F showed skin burn breakage. Two weeks after the completion of irradiation, there was no obvious discoloration on the dorsal skin of BALB/c female mice in all groups. In C57BL/6JNifdc female mice, group D showed no obvious discoloration, group E exhibited lighter discoloration compared to the 4th week post-irradiation, and group F had crusted skin at the burn sites with lighter discoloration than before. However, the discoloration in groups E and F was still obviously visible to the naked eye. HE staining showed that the difference in the thickness of the echinocyte layer was not statistically significant in groups A, B, C, and G ( H=1.08, P=0.782); whereas the difference was statistically significant in groups D, E, F and H ( H=12.85, P=0.005). The thickness of the echinocyte layer decreased gradually with the extension of the irradiation time. Additionally, there was a disruption in the arrangement of epidermal spindles in group F, and this situation was not observed in groups D and E. Masson-Fontana staining revealed no significant pigmentation in any of the BALB/c female mice. The difference in melanin granule counts between groups A, B, C, and G was not statistically significant ( H=7.77, P=0.051). In contrast, C57BL/6JNifdc female mice exhibited more noticeable pigmentation in the epidermis and dermis in groups E and F. The difference in melanin particle counts among groups D, E, F and H was statistically significant ( H=17.61, P<0.001), with melanin deposition increasing gradually with the duration of irradiation. Masson staining showed that the difference in collagen percentage between groups A, B, C, and G was not statistically significant ( H=7.26, P=0.064). However, significant disorganization of fibers and a loose structure were observed in groups E and F. The difference in collagen percentage between groups D, E, F, and H was statistically significant ( H=8.65, P=0.034). Immunohistochemical results showed that the difference in IL-1 expression levels between groups A, B, C, and G was statistically significant ( H=17.86, P<0.001); also between groups D, E, F, and H was statistically significant ( H=14.19, P=0.003), suggesting that ultraviolet irradiation stimulated an inflammatory response in the skin of mice. Conclusion:BALB/c female mice are not suitable for melasma models under the frequency and duration of irradiation in this experiment. C57BL/6JNifdc female mice are irradiated with a single irradiation energy dose of 7.59 J/cm 2 five days a week for 4 weeks, which can establish stable animal models of melasma with a specific level of pigmentation that persisted for at least 2 weeks.

Objective:To develop a virtual reality (VR) exercise rehabilitation system for home-based patients with spinal cord injury, and test patients' acceptance and experience.Methods:The VR exercise rehabilitation system for home-based patients with spinal cord injury was developed by a multidisciplinary team based on the home rehabilitation needs, evidence, and clinical experience of spinal cord injury patients, and further improved after recommendations from experts and patients. From February to July 2024, convenience sampling was used to select 148 patients with spinal cord injuries admitted to the Department of Spinal Cord and Neurological Function Reconstruction at the China Rehabilitation Research Center. Acceptance Questionnaire was used to investigate patients' acceptance of the system. Thirteen patients with spinal cord injuries were selected for semi-structured interviews to explore the themes of their experiences using VR exercise rehabilitation system for home-based patients with spinal cord injury.Results:A VR exercise rehabilitation system for home-based patients with spinal cord injury was developed, which includes four aspects of personal profile, personal assessment, training selection, and care knowledge. The total acceptance score of this system among 148 patients was (87.69±1.59). Through semi-structured interviews, three themes were identified involving excellent experience, expectation of rehabilitation effects, satisfaction with functionality and hope for continuous system updates.Conclusions:The design of VR exercise rehabilitation system for home-based patients with spinal cord injury is scientifically reasonable, which can further verify the rehabilitation effect of the system.

Objective To explore the automated identification and diameter measurement methods for inferior vena cava (IVC) based on clinical ultrasound images of IVC. Methods An automated identification and localization method based on topology and automatic tracking algorithm was proposed. Tracking algorithm was used for identifying and continuously locating to improve the efficiency and accuracy of measurement. Tests were conducted on 18 sets of ultrasound data collected from 18 patients in intensive care unit (ICU),with clinicians' measurements as the gold standard. Results The recognition accuracy of the automated method was 94.44％ (17/18),and the measurement error of IVC diameter was within the range of±1.96s (s was the standard deviation). The automated method could replace the manual method. Conclusion The proposed IVC automated identification and localization algorithm based on topology and automatic tracking algorithm has high recognition success rate and IVC diameter measurement accuracy. It can assist clinicians in identifying and locating IVC,so as to improve the accuracy of IVC measurement.

Objective:To determine the optimal irradiation energy and frequency for the establishment of melasma mouse model using simple ultraviolet irradiation, and to provide guidance on animal strains and irradiation protocols for the successful establishment of melasma model.Methods:Animal models of melasma were established using BALB/c female mice and C57BL/6JNifdc female mice. BALB/c female mice were divided into 4 groups using a simple randomization method: A, B, C and G, with 5 mice in each group. C57BL/6JNifdc female mice were divided into 4 groups: D, E, F and H, with 5 mice in each group. All mice were irradiated with 8.428 mW/cm 2 of ultraviolet light. The irradiation time was 15 s (single irradiation energy of 0.13 J/cm 2) in groups A and D, 15 min (single irradiation energy of 7.59 J/cm 2) in groups B and E, and 30 min (single irradiation energy of 15.17 J/cm 2) in groups C and F. Each cycle consisted of 5 consecutive days of irradiation followed by 2 days of cessation, totaling 4 cycles of irradiation. Groups G and H were not irradiated. At the end of irradiation, all mice were kept under normal conditions. One week later, 3 mice from each group were selected for HE, Masson-Fontana, Masson, and immunohistochemical staining. Quantitative analysis was performed to measure the thickness of the acanthocyte layer, melanin granules, collagen percentage, and interleukin-1 (IL-1) levels. The remaining mice were kept for an additional week, depilated and photographed to observe the changes in coloration. Data were analyzed using SPSS 27.0 software, measurement data that did not conform to normal distribution were represented by M( Q1, Q3) and comparisons between groups were made using the Kruskal-Wallis rank sum test. Results:During the entire irradiation process, no visible discoloration was observed in the BALB/c female mice in all groups. In contrast, varying sizes of discoloration appeared in the C57BL/6JNifdc female mice in groups D, E, and F after irradiation in the second week. However, by the third week, the discoloration in group D gradually disappeared, while the discoloration in group E was more obvious than before. At the same time, group F exhibited significant discoloration, with some mice exhibited signs of skin peeling, burning and breakage on their backs. After the 4th week of irradiation, no new discoloration was formed in group D. The discoloration was more obvious in group E, and most mice in group F showed skin burn breakage. Two weeks after the completion of irradiation, there was no obvious discoloration on the dorsal skin of BALB/c female mice in all groups. In C57BL/6JNifdc female mice, group D showed no obvious discoloration, group E exhibited lighter discoloration compared to the 4th week post-irradiation, and group F had crusted skin at the burn sites with lighter discoloration than before. However, the discoloration in groups E and F was still obviously visible to the naked eye. HE staining showed that the difference in the thickness of the echinocyte layer was not statistically significant in groups A, B, C, and G ( H=1.08, P=0.782); whereas the difference was statistically significant in groups D, E, F and H ( H=12.85, P=0.005). The thickness of the echinocyte layer decreased gradually with the extension of the irradiation time. Additionally, there was a disruption in the arrangement of epidermal spindles in group F, and this situation was not observed in groups D and E. Masson-Fontana staining revealed no significant pigmentation in any of the BALB/c female mice. The difference in melanin granule counts between groups A, B, C, and G was not statistically significant ( H=7.77, P=0.051). In contrast, C57BL/6JNifdc female mice exhibited more noticeable pigmentation in the epidermis and dermis in groups E and F. The difference in melanin particle counts among groups D, E, F and H was statistically significant ( H=17.61, P<0.001), with melanin deposition increasing gradually with the duration of irradiation. Masson staining showed that the difference in collagen percentage between groups A, B, C, and G was not statistically significant ( H=7.26, P=0.064). However, significant disorganization of fibers and a loose structure were observed in groups E and F. The difference in collagen percentage between groups D, E, F, and H was statistically significant ( H=8.65, P=0.034). Immunohistochemical results showed that the difference in IL-1 expression levels between groups A, B, C, and G was statistically significant ( H=17.86, P<0.001); also between groups D, E, F, and H was statistically significant ( H=14.19, P=0.003), suggesting that ultraviolet irradiation stimulated an inflammatory response in the skin of mice. Conclusion:BALB/c female mice are not suitable for melasma models under the frequency and duration of irradiation in this experiment. C57BL/6JNifdc female mice are irradiated with a single irradiation energy dose of 7.59 J/cm 2 five days a week for 4 weeks, which can establish stable animal models of melasma with a specific level of pigmentation that persisted for at least 2 weeks.

OBJECTIVE: To explore the clinical and genetic features of a child with autosomal dominant mental retardation type 40 (MRD40) due to variant of the CHAMP1 gene. METHODS: Clinical characteristics of the child were analyzed. Genetic testing was carried out by low-depth high-throughput and whole genome copy number variant sequencing (CNV-seq) and whole exome sequencing (WES). A literature review was also carried out for the clinical phenotype and genetic characteristics of patients with MRD40 due to CHAMP1 gene variants. RESULTS: The child, a 11-month-old girl, has presented with intellectual and motor developmental delay. CNV-seq revealed no definite pathogenic variants. WES has detected the presence of a heterozygous c.1908C>G (p.Y636*) variant in the CHAMP1 gene, which was carried by neither parent and predicted to be pathogenic. Literature review has identified 33 additional children from 12 previous reports. All children had presented with developmental delay and mental retardation, and most had dystonia (94.1%), delayed speech and/or walking (85.2%, 82.4%) and ocular abnormalities (79.4%). In total 26 variants of the CHAMP1 gene were detected, with all nonsense variants being of loss-of-function type, located in exon 3, and de novo in origin. CONCLUSION The heterozygous c.1908C>G (p.Y636*) variant of the CHAMP1 gene probably underlay the WRD40 in this child. Genetic testing should be considered for children featuring global developmental delay, mental retardation, hypertonia and facial dysmorphism.
Humans ; Intellectual Disability/genetics* ; Genetic Testing ; Phenotype ; Exome Sequencing ; Heterozygote ; Mutation ; Chromosomal Proteins, Non-Histone/genetics* ; Phosphoproteins/genetics*

Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.
Humans ; Antineoplastic Agents/therapeutic use* ; Apoptosis ; beta Catenin/metabolism* ; Biomarkers, Tumor/metabolism* ; Cell Line, Tumor ; Coenzyme A Ligases/metabolism* ; Leukemia, Myeloid, Acute/metabolism* ; Lipoylation ; Prognosis ; Wnt Signaling Pathway

Objective:To detect and analyze the gene variation types of 64 unrelated pedigrees affected with autosomal dominant polycystic kidney disease (ADPKD), and explore the detection efficiency of multiple gene analysis techniques and variation characteristics.Methods:It was a cross-sectional study. The clinical data of 64 pedigrees with ADPKD from Nephrology Department or Genetic and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from December 2017 to August 2020 were retrospectively analyzed. The blood samples of probands and other family members were collected. Genetic analysis was carried out by next generation sequencing, and suspected mutations were verified by multiplex ligation-dependent probe amplification, or long-range PCR combined with Sanger sequencing. Prenatal diagnosis for high-risk fetuses was performed by fetal villi or amniotic fluid cells after genotyping without maternal genomic DNA contamination.Results:Among detected 64 pedigrees, 57 pedigrees (89.06%) had genetic variants in PKD1/PKD2. A total of 49 pathogenic/likely pathogenic variants in PKD1/PKD2 were identified in 51 pedigrees (79.69%), including 14 nonsense variants (28.57%), 14 frameshift variants (28.57%), 11 missense variants (22.45%), 5 splicing variants (10.20%) and 5 deletion variants (10.20%). Of these variants, 87.76% (43/49) were in PKD1 and 12.24% (6/49) were in PKD2. Totally, 14 novel variants in PKD1/ PKD2 were identified, including 7 frameshift variants, 3 splicing variants, 2 nonsense variants, 1 deletion variant and 1 missense variant, of which 11 variants were in PKD1 and 3 variants were in PKD2. Twenty high-risk fetuses from 17 pedigrees received prenatal diagnosis, in whom 6 fetuses had PKD1 variation, and other 14 fetuses had no PKD1/ PKD2-genetic variation. Conclusions:The combination of next-generation sequencing, multiplex ligation-dependent probe amplification, and long-range PCR combined with Sanger sequencing can be helpful for rapid, efficient and accurate genetic diagnosis of ADPKD pedigrees. Point mutations are the most common types in PKD1/PKD2. Fourteen novel variants in PKD1/PKD2 extend its pathogenic variant spectrum and can provide basis for genetic counseling and prenatal diagnosis of ADPKD pedigrees.

Gastrointestinal cancers are the common malignant tumors of the digestive system, and their morbidity and mortality are in the forefront of malignant tumors. Currently, cancer immunotherapy is the hottest topic in cancer research field. Although cancer immunotherapy has achieved some results in the fundamental research and clinical application of gastrointestinal tumors, there are still a series of problems that need to be resolved. In this article, we review the fundamental and clinical research progress of several common methods of cancer immunotherapy in the field of gastrointestinal tumors.

Background: The incidence of ulcerative colitis (UC) has gradually increased in China in recent years. The pathogenesis of UC is related to the dysfunction of immune system. B7-H5 is an important immune checkpoint molecule and is significant for the regulation of immune function. Ainis: To investigate the expression and clinical significance of B7-H5 in UC. Methods: A total of 65 UC tissue specimens were collected from Jan. 2010 to Dec. 2020 at the First Affiliated Hospital of Soochow University, and 5 healthy subjects were served as controls. Immunohistoehemistry and immunofluorescence were used to detect the expression of B7-H5, and its relationship with elinieopathologieal characteristics of UC patients was analyzed. Results: Expression of B7-H5 was significantly increased in UC patients than in controls (P < 0. 001). B7-H5 expression in UC patients was positively correlated with ESR and CRP (P < 0. 01), but not related to gender, age, extent of lesion, Mayo score and UCEIS score (P > 0. 05). Conclusions; The expression of B7-H5 in UC patients is significantly increased and is correlated with ESR and CRP, and can be used as a new marker for reflecting the severity of inflammation in UC patients.