Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

Objective:To explore the application of medical dialectics combined with problem-oriented teaching based on textbooks in hematology internship teaching.Methods:A total of 100 undergraduate students who practiced in the Department of Hematology of the First Hospital of Jilin University from 2022 to 2023 were selected as the research subjects. Students were randomly assigned to a control group and an observation group, with 50 students in each group. The control group received traditional teaching, while the observation group received medical dialectics combined with textbook-based problem-oriented teaching. We assessed the theoretical and operational scores, classroom performance, comprehensive abilities, and teaching satisfaction of two groups of students using t-test and χ 2 test in SPSS 22.0. Results:The theoretical and operational scores of the observation group were (94.26±5.35) points and (92.68±4.72) points, respectively. The theoretical and operational scores of the control group were (86.16±5.42) points and (81.52±5.28) points, respectively. The differences between the two groups were statistically significant ( P<0.001). The recognition rates were significantly higher by students in the observation group than in the control group ( P<0.05) in terms of improving learning efficiency, self-learning ability, understanding and comprehensive analysis of diseases, problem-solving ability, language and organizational expression ability, integration of theory and practice, clinical thinking ability, and independent thinking ability. The satisfaction with teaching was higher in the observation group than in the control group ( P<0.05) in terms of teaching attitudes, teaching methods, teaching arrangements, practicality of teaching content, clear explanation of teaching theories, and outstanding teaching objectives. Conclusions:The medical dialectics combined with textbook-based problem-oriented teaching can improve the assessment scores of medical students, while helping to cultivate their comprehensive abilities and develop good clinical diagnosis and treatment thinking.

Objective Use of silencing information regulatory factor 1(SIRT1)/high mobility group protein B1(HMGB1)/nuclear transcription factor-KB(NF-κB)to investigate the inhibitory effect and mechanism of Salvia miltiorrhiza Bunge gynostemma pentaphyllum tea on hepatocyte inflammatory apoptosis in mice with carbon tetrachloride(CC14)-induced acute liver injury.Methods C57BL/6 mice were randomly divided into a control group;model group;resveratrol group;Salvia miltiorrhiza Bunge gynostemma pentaphyllum tea low-,medium-,and high-dose groups;and a positive drug group.The mice were given continuous intragastric administration of the treatments for 14 days.An acute liver injury model was established by intraperitoneal injection of 0.5％CC14 olive oil solution(5 mL/kg).The levels of alanine transferase(ALT),aspartate transferase(AST),lactate dehydrogenase(LDH)in serum and hydroxyproline(Hyp),malondialdehyde(MDA),and superoxide dismutase(SOD)in the liver were determined by biochemical method.Serum levels of inflammatory tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-1 β were determined by enzyme-linked immunosorbent assay.Eosin-hematoxylin and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling(TUNEL)staining were used to examine the pathological morphology and apoptosis in liver tissues.The protein expression of SIRT1,HMGB1,and NF-κB were detected by Western Blot.Results Compared with those of the control group,the model group's serum ALT,AST,and LDH levels and liver tissue Hyp activity were significantly increased;MDA and SOD activities in liver tissue were significantly decreased;the levels of inflammatory factors TNF-α,IL-6,and IL-1 β in liver tissue were significantly increased;and there were obvious signs of pathological injury and hepatocyte apoptosis in the liver tissue.The expression of SIRT1 protein decreased significantly,while the expression of HMGB1 and NF-κB proteins increased,in liver tissue.Compared with those of the model group,the Salvia miltiorrhiza Bunge gynostemma pentaphyllum tea high group and resveratrol group serum levels of ALT,AST,and LDH and liver tissue Hyp activity were significantly decreased;MDA and SOD activities in liver tissue were significantly increased;the levels of serum inflammatory factors TNF-α,IL-6,and IL-1β were decreased;and pathological injury to liver tissue and the apoptosis of liver cells were significantly improved.The expression of SIRT1 protein in liver tissue was increased,while the expression of HMGB1 and NF-κB protein were decreased in the Salvia miltiorrhiza Bunge gynostemma pentaphyllum tea high-dose group and resveratrol group(P＜0.05 or P＜0.01).Conclusions Salvia miltiorrhiza Bunge gynostemma pentaphyllum tea effectively protects against acute liver injury,and its mechanisms may be related to the regulation of the SIRT1/HMGB1/NF-κB signaling pathway and the alleviation hepatocyte inflammatory apoptosis.

Objective Use of silencing information regulatory factor 1(SIRT1)/high mobility group protein B1(HMGB1)/nuclear transcription factor-KB(NF-κB)to investigate the inhibitory effect and mechanism of Salvia miltiorrhiza Bunge gynostemma pentaphyllum tea on hepatocyte inflammatory apoptosis in mice with carbon tetrachloride(CC14)-induced acute liver injury.Methods C57BL/6 mice were randomly divided into a control group;model group;resveratrol group;Salvia miltiorrhiza Bunge gynostemma pentaphyllum tea low-,medium-,and high-dose groups;and a positive drug group.The mice were given continuous intragastric administration of the treatments for 14 days.An acute liver injury model was established by intraperitoneal injection of 0.5％CC14 olive oil solution(5 mL/kg).The levels of alanine transferase(ALT),aspartate transferase(AST),lactate dehydrogenase(LDH)in serum and hydroxyproline(Hyp),malondialdehyde(MDA),and superoxide dismutase(SOD)in the liver were determined by biochemical method.Serum levels of inflammatory tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-1 β were determined by enzyme-linked immunosorbent assay.Eosin-hematoxylin and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling(TUNEL)staining were used to examine the pathological morphology and apoptosis in liver tissues.The protein expression of SIRT1,HMGB1,and NF-κB were detected by Western Blot.Results Compared with those of the control group,the model group's serum ALT,AST,and LDH levels and liver tissue Hyp activity were significantly increased;MDA and SOD activities in liver tissue were significantly decreased;the levels of inflammatory factors TNF-α,IL-6,and IL-1 β in liver tissue were significantly increased;and there were obvious signs of pathological injury and hepatocyte apoptosis in the liver tissue.The expression of SIRT1 protein decreased significantly,while the expression of HMGB1 and NF-κB proteins increased,in liver tissue.Compared with those of the model group,the Salvia miltiorrhiza Bunge gynostemma pentaphyllum tea high group and resveratrol group serum levels of ALT,AST,and LDH and liver tissue Hyp activity were significantly decreased;MDA and SOD activities in liver tissue were significantly increased;the levels of serum inflammatory factors TNF-α,IL-6,and IL-1β were decreased;and pathological injury to liver tissue and the apoptosis of liver cells were significantly improved.The expression of SIRT1 protein in liver tissue was increased,while the expression of HMGB1 and NF-κB protein were decreased in the Salvia miltiorrhiza Bunge gynostemma pentaphyllum tea high-dose group and resveratrol group(P＜0.05 or P＜0.01).Conclusions Salvia miltiorrhiza Bunge gynostemma pentaphyllum tea effectively protects against acute liver injury,and its mechanisms may be related to the regulation of the SIRT1/HMGB1/NF-κB signaling pathway and the alleviation hepatocyte inflammatory apoptosis.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective: To investigate clinical characteristics and treatment of phytophotodermatitis due to ingesting Chenopodium album. Methods: This study included 11 patients with phytophotodermatitis caused by ingesting Chenopodium album collected from Department of Dermatology, Affiliated Hospital of Jining Medical University from 2013 to 2017. The patients′ general information, clinical manifestations, laboratory test results, treatment and prognosis were retrospectively analyzed. Results: All the 11 patients were female, and their age ranged from 45 to 62 years. They all had a history of ingesting Chenopodium album and exposing to sunlight within 1 - 2 days prior to the disease onset. Clinical manifestations included symmetrically distributed, painful and pruritic, nonpitting, swelling erythema on the face and back of both hands and at sunexposed sites of forearms, with a tense and bright surface. Increased white blood cell counts were observed in 6 patients, and increased eosinophil counts in 1. All of the 11 patients were treated with systemic methylprednisolone, loratadine, ebastine, spironolactone, furosemide and omeprazole as well as topical agents, 2 also received human immunoglobulin treatment, and 3 were also treated with oral ibuprofen and codeine for painful lesions. Ten patients received obvious improvement and were discharged after 7 - 10 days of treatment, and no pigmentation or scars were observed after 1-year follow-up. Skin necrosis occurred on the back of both hands in 1 patient after 7-day treatment, and scars remained in the patient after follow-up of half a year. Conclusions Chenopodium album-induced phytophotodermatitis commonly manifests as swelling erythema on the exposed body sites. After confirmed diagnosis, Chenopodium album ingestation and sunlight exposure should be avoided, and timely antianaphylactic treatment should be considered to effectively control the disease.

Objective: To analyze ¹⁸F-fluorodeoxyglucose(FDG) PET/CT imaging manifestations in patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC) and investigate its clinical significance. Methods: From May 2016 to August 2018, 46 patients (25 males, 21 females; age range: 36-82(62.0±10.4) years) with PC from CRC who underwent ¹⁸F-FDG PET/CT imaging in Affiliated Hospital of Nantong University and had complete clinical data were retrospectively analyzed. The peritoneal carcinomatosis index (PCI) grading system was used to evaluate the PC lesions. Independent-sample t test and Kruskal-Wallis H test were used for data analysis. Results: There were various CT manifestations of PC, while FDG metabolism on PET was observed in all 46 patients. Patients were divided into different groups according to the location of the primary CRC lesion. The diameter of PC lesion in the left colon group was (2.46±1.26) cm, which was significantly different from that of the rectum group ((3.19±1.72) cm; t=-2.77, P<0.01). The maximum standardized uptake value (SUV_max) in the right colon group were significantly higher than that in the left colon group (9.16±4.79 vs 6.99±3.50; t=2.92, P<0.01). The PCI score ranged from 1 to 30 in 46 patients, and there was no significant difference in PCI score distribution (≥20 vs <20) among the right colon group, left colon group and rectum group (H=0.242, P>0.05). Ten patients had abdominal and pelvic effusion. Conclusion ¹⁸F-FDG PET/CT can well display the PC in patients with CRC, and the combination of PCI and ¹⁸F-FDG PET/CT plays an important role in the diagnosis and treatment of PC.

Objective To explore the risk factors of pulmonary artery hypertension (PAH) and the its relationship with T cell subsets to provide a foundation for the prevention and treatment of PAH.Methods 154 maintained hemodialysis (MHD) patients in our dialysis center were recruited according to the criterion and divided into two groups subsequently:PAH group (pulmonary artery systolic pressure,PASP ＞ 35 mmHg) and non-PAH group (PASP≤35 mmHg).The related clinical,biochemical and ultrasonic cardiogram data were collected and peripheral blood was acquired to detect the expressions of the surface antigen CD3,CD4,CD8 and CD69 with flow cytometry.Logistic regression analysis was used to find out the relationship between PAH and T cell subsets.Results There was no significant difference between 56 cases of PAH and 98 cases of non-PAH as regards gender,age,mean systolic and diastolic pressure,dialysis durations,morbidities of hypertension and diabetes,smoking rate,and left ventricular diameter.Compared with the non-PAH group,the PAH group demonstrated a lower percent of CD8 T cells and CD8 CD69 T cells,but a much higher left atrial diameter (LAD),Interventricular septum thickness,left ventricular posterior wall thickness,and NT-proBNP.The percentage of T cells,CD4 T cells and CD4 CD69 T cells showed no difference between the two groups.Multivariate analysis confirmed that PAH was negatively independently associated with the percentage of CD8 T cells and CD8CD69 T cells.Conclusions The decreased percentage of CD8 T cells and CD8CD69 T cells in the peripheral blood is a risk factor of PAH in maintained hemodialysis patients,and CD8 T cells may play an important role in the genesis of PAH.

AIM:To observe the effects of adipose differentiation-related protein ( adipophilin) on the expres-sion of inflammatory factors in RAW264.7 macrophage and to clarify the related mechanism.METHODS:The cell models with high expression and low expression of adipophilin were constructed by transfecting PA317 packaging cells with stable high or low expression adipophilin retroviral vectors into the RAW264.7 cells.The concentrations of IL-6, MCP-1 and TNF-αin the cell culture medium were detected by ELISA.The protein levels of AP-1, p-AP-1, ERK1/2 and p-ERK1/2 were measured by Western blot.The protein levels of adipophilin, p-ERK1/2 and p-AP-1 and the releases of the inflamma-tory factors in the RAW264.7 cells treated with or without ERK1/2 inhibitor PD98059 or AP-1 inhibitor curcumin were de-termined.RESULTS:The RAW264.7 cells with high expression of adipophilin had higher levels of IL-6, MCP-1 and TNF-α, and higher protein levels of p-AP-1 and p-ERK1/2 than those in the cells with low expression of adipophilin. ERK1/2 inhibitor had no significant effect on the expression of adipophilin, but the protein expression of ERK1/2 and AP-1 was significantly inhibited (P<0.05).The administration of AP-1 inhibitor curcumin had no significant effect on the protein expression of adipophilin and ERK1/2, but the protein expression of AP-1 was significantly inhibited (P<0.05). At the same time, the releases of inflammatory factors IL-6, MCP-1 and TNF-αwere significantly decreased.CONCLU-SION:Adipophilin may regulate the expression of inflammatory factors through ERK1/2-AP-1 pathway in RAW264.7 mac-rophages.