ObjectiveBased on functional near-infrared spectroscopy (fNIRS), we investigated the brain activity characteristics of gross motor tasks in children with autism spectrum disorder (ASD) and motor dysfunctions (MDs) to provide a theoretical basis for further understanding the mechanism of MDs in children with ASD and designing targeted intervention programs from a central perspective. MethodsAccording to the inclusion and exclusion criteria, 48 children with ASD accompanied by MDs were recruited into the ASD group and 40 children with typically developing (TD) into the TD group. The fNIRS device was used to collect the information of blood oxygen changes in the cortical motor-related brain regions during single-handed bag throwing and tiptoe walking, and the differences in brain activation and functional connectivity between the two groups of children were analyzed from the perspective of brain activation and functional connectivity. ResultsCompared to the TD group, in the object manipulative motor task (one-handed bag throwing), the ASD group showed significantly reduced activation in both left sensorimotor cortex (SMC) and right secondary visual cortex (V2) (P<0.05), whereas the right pre-motor and supplementary motor cortex (PMC&SMA) had significantly higher activation (P<0.01) and showed bilateral brain region activity; in terms of brain functional integration, there was a significant decrease in the strength of brain functional connectivity (P<0.05) and was mainly associated with dorsolateral prefrontal cortex (DLPFC) and V2. In the body stability motor task (tiptoe walking), the ASD group had significantly higher activation in motor-related brain regions such as the DLPFC, SMC, and PMC&SMA (P<0.05) and showed bilateral brain region activity; in terms of brain functional integration, the ASD group had lower strength of brain functional connectivity (P<0.05) and was mainly associated with PMC&SMA and V2. ConclusionChildren with ASD exhibit abnormal brain functional activity characteristics specific to different gross motor tasks in object manipulative and body stability, reflecting insufficient or excessive compensatory activation of local brain regions and impaired cross-regions integration, which may be a potential reason for the poorer gross motor performance of children with ASD, and meanwhile provides data support for further unraveling the mechanisms underlying the occurrence of MDs in the context of ASD and designing targeted intervention programs from a central perspective.

OBJECTIVE: To retrospectively analyze the clinical characteristics, co-mutated genes in newly diagnosed acute myeloid leukemia (AML) patients with NRAS and KRAS gene mutations, and the impact of NRAS and KRAS mutations on prognosis. METHODS: The clinical data and next-generation sequencing results of 80 newly diagnosed AML patients treated at our hospital from December 2018 to December 2023 were collected. The clinical characteristics, co-mutated genes of NRAS and KRAS , and the impact of NRAS and KRAS mutations on prognosis in newly diagnosed AML patients were analyzed. RESULTS: Among 80 newly diagnosed AML patients, NRAS mutations were detected in 20 cases(25.0%), and KRAS mutations were detected in 9 cases(11.3%). NRAS mutations predominantly occurred at codons 12 and 13 of exon 2, as well as codon 61 of exon 3, while KRAS mutations were most commonly occurred at codons 12 and 13 of exon 2, all of which were missense mutations. There were no statistically significant differences observed in terms of age, sex, white blood cell count(WBC), hemoglobin(Hb), platelet count(PLT), bone marrow blasts, first induction chemotherapy regimen, CR1/CRi1 rates, chromosome karyotype, 2022 ELN risk classification and allogeneic hematopoietic stem cell transplantation(allo-HSCT) among the NRAS mutation group, KRAS mutation group and NRAS/KRAS wild-type group (P >0.05). KRAS mutations were significantly correlated with PTPN11 mutations (r =0.344), whereas no genes significantly associated with NRAS mutations were found. Survival analysis showed that compared to the NRAS/KRAS wild-type group, patients with NRAS mutation had a relatively higher 5-year overall survival (OS) rate and relapse-free survival (RFS) rate, though the differences were not statistically significant (P =0.097, P =0.249). Compared to the NRAS/KRAS wild-type group, patients with KRAS mutation had a lower 5-year OS rate and RFS rate, with no significant differences observed (P =0.275, P =0.442). There was no significant difference in the 5-year RFS rate between the KRAS mutation group and NRAS mutation group (P =0.157), but the 5-year OS rate of patients with KRAS mutation was significantly lower than that of patients with NRAS mutation (P =0.037). CONCLUSION In newly diagnosed AML patients, KRAS mutation was significantly correlated with PTPN11 mutation. Compared to patients with NRAS/KRAS wild-type, those with NRAS mutation showed a more favorable prognosis, while patients with KRAS mutation showed a poorer prognosis; however, these differences did not reach statistical significance. Notably, the prognosis of AML patients with KRAS mutation was significantly inferior compared to those with NRAS mutation.
Humans ; Leukemia, Myeloid, Acute/diagnosis* ; Mutation ; Prognosis ; Proto-Oncogene Proteins p21(ras)/genetics* ; GTP Phosphohydrolases/genetics* ; Retrospective Studies ; Membrane Proteins/genetics* ; Female ; Male ; Middle Aged ; Adult ; Aged

Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.
Reperfusion Injury/drug therapy* ; Reactive Oxygen Species/metabolism* ; Reactive Nitrogen Species/metabolism* ; Humans ; Liver/drug effects* ; Animals ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

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Constipation is a prevalent ailment which might significantly impact the quality of people's life and rise some associated deseases risks. In this study, a chronic constipation mouse model was established using loperamide hydrochloride. Mice were gavaged an Angelica sinensis Cistanche Fiber Compound, comprised of Dang Gui [Angelica sinensis (Oliv.) Diels], Rou Cong Rong (Cistanche deserticola Y.C.Ma), wheat fiber, and low-molecular-weight xylan at high dosage (3.6 g·kg^-1, 30 times the recommended human dose) and low dosage (0.6 g·kg^-1, 5 times the recommended human dose) for 14 days. The study assessed the therapeutic efficacy of the compound by observing fecal morphology, measuring water content, and conducting small intestine motility experiments. Furthermore, enzyme-linked immunosorbent assays (ELISA) were conducted to evaluate the serum levels of gastrointestinal hormones including motilin (MTL), gastrin (GAS), the inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Histopathological examination with H&E staining was employed to evaluate colonic tissue damage. Additionally, Western blot and immunohistochemistry experiments were conducted to examine the expression levels of aquaporin-3 (AQP3) and c-Kit in the colon. The results indicated that the Angelica sinensis Cistanche Fiber Compound could improve fecal morphology, increase fecal water content, enhance small intestinal transit rates in mice. Additionally, there was a significant elevation in the serum levels of gastrointestinal hormones and a notable reduction in the levels of inflammatory factors. The improvement in colonic histopathological damage was accompanied by a marked decrease in the expression of the colonic water channel protein AQP3 and a significant increase in c-Kit expression. These results collectively suggested the presence of a dose-response relationship. These findings indicate that the Angelica sinensis Cistanche Fiber Compound effectively alleviates constipation in mice. Its action is associated with the regulation of colonic water channel protein AQP3 and c-Kit expression, along with the modulation of serum inflammatory factors and gastrointestinal hormones. This experiment was approved by the Animal Experiment Ethics Committee of Jinan University.

Objective:To evaluate the reliability and validity of the Chinese version of HEMO-FISS-QoL(HF-QoL) questionnaire (HF-QoL-C) in the Chinese population with hemorrhoids.Methods:From November 2021 to November 2022, a self-constructed general information questionnaire, HF-QoL-C, and the 36-item short form health survey (SF-36), Goligher classification, and Giordano severity of hemorrhoid symptom questionnaire (GSQ) were used to conduct a questionnaire survey on 760 hemorrhoid patients in the anorectal department of six hospitals. The data was analyzed for reliability and validity using SPSS 21.0 and AMOS 26.0 software.Results:The Cronbach's α coefficient of HF-QoL-C and its dimension ranged from 0.831 to 0.960, and the split coefficient was 0.832-0.915. Four common factors were extracted through principal component exploratory factor analysis. Confirmatory factor analysis indicated acceptable structural validity( χ2/ df=8.152, RSMEA=0.097, CFI=0.881, IFI=0.881, NFI=0.867). HF-QoL-C was correlated with SF36 and GSQ( r=-0.694, 0.501, both P<0.01). There were differences in the total score and dimensional scores of HF-QoL-C between surgical and drug treated patients, different grades of Goligher classification for hemorrhoidal disease, and different ranges of hemorrhoid prolapse (all P<0.001). No ceiling effect was found in the total score and the scores of each dimension(0.3%-2.0%). There was a floor effect in both psychological function and sexual activity dimensions (16.7%, 35.1%). Conclusion:HF-QoL-C has good reliability and validity, which can be used to measure the quality of life of Chinese hemorrhoid patients.

Objective To evaluate the predictors of biochemical recurrence after laparoscopic radical prostatectomy.Methods The study cohort consisted of 416 consecutive prostatecancer patients who underwent radical prostatectomy in Zhongshan Hospital,Fudan University between Jan 2016 and Jun 2018.No patient received adjuvant therapy until documented biochemical recurrence.Biochemical recurrence-free survival(BCRFS)was estimated using the Kaplan-Meier method.Univariable and multivariable Cox proportional hazards regression models were utilized to determine variables predictive of biochemical recurrence.Results The median follow-up period was 174 weeks(inter quartile range 133-209 weeks).The overall biochemical recurrence rate was 21.39%(88/416).The time to biochemical recurrence was(51.11±47.71)weeks.Until the end of follow-up,the biochemical recurrence rates were 10%(1/10),6.12%(3/49),16.41%(43/262)and 43.16%(41/95)for low-risk,medium-risk,high-risk and locally advanced prostate cancer,respectively.On multivariable analysis,tumor invasion of the seminal vesicles(HR:2.119,95%CI:1.154-3.891,P=0.016);Seminal vesicle invasion(HR:1.824,95%CI:1.034-3.220,P=0.038),Gleason score≥8(HR:2.746,95%CI:1.268-5.943,P=0.010),prostate-specific antigen(PSA)=10-20 ng/mL(HR:4.240,95%CI:2.550-7.050,P<0.001);PSA>20 ng/mL(HR:6.341,95%CI:3.296-12.202,P<0.001)were the main predictors of biochemical recurrence.Conclusion Laparoscopic radical prostatectomy provides effective control of biochemical recurrence during the mid-term follow-up period.Tumor invasion of the seminal vesicles,seminal vesicle invasion,GS≥8,PSA=10-20 ng/mL,PSA>20 ng/mL were important predictors of biochemical recurrence after radical prostatectomy.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Objective:To discuss the clinical presentations,diagnosis,and treatment methods of the patients with Fournier's gangrene,and to enhance the clinicians'awareness of this condition.Methods:The clinical data including symptoms,signs,radiological findings,and surgical outcomes of one patient with Fournier's gangrene were collected.The relevant literatures were reviewed to summarize the clinical characteristics,diagnosis,and treatment methods for this condition.Results:The patient,a 42-year-old male,was admitted because of a history of infection around the perineum,scrotum,and perianal area for 13 d.His medical history included acute myeloid leukemia for 10 months,during which the patient underwent eight chemotherapy sessions in the local hospital.The abdominal CT scan results showed thickened,dense,and turbid soft tissue in the left inguinal area.The complete blood count reuslts showed the white blood cell count was 23.99×109 L-1.The cultures of wound secretions grew the Escherichia coli and Proteus mirabilis.The examination results showed there was necrosis of the scrotal skin and skin near the anus on the left buttock;the skin was blackened,hard,and demarcated from the surrounding normal skin with slight purulent exudation and no foul smell.The surrounding skin was significantly swollen and red;the rectal examination results showed no bleeding or fistulas.The patient underwent emergency debridement surgery on the admission day,followed by dressing changes,multiple applications of simplified negative pressure,perineal flap reconstruction,and skin grafting.The patient recovered well with normal function and had no complications.Conclusion:Fournier gangrene has acute onset and rapid progression,and the clinical manifestations are non-specific.The range of infection is not consistent with the progression of the disease.The diagnosis mainly depends on intraoperative exploration.Repeated radical surgery is the main treatment.The prognosis of this disease is good,and the recurrence rate is low,although long-term follow-up is still necessary after surgery.

Objective To investigate the improvement effect and mechanism of marmesin on cognitive impairment in Alzheimer's disease(AD)mice.Methods Fifty mice were randomly divided into five groups:blank group,model group,low-and high-dose marmesin groups and donepezil(positive drug)group,with 10 mice in each group.After 21 days of continuous administration,except for the blank group,the mice in other groups were given intraperitoneal injection of scopolamine to establish the AD model.Network pharmacology was used to construct the protein-protein interaction(PPI)network of common targets of marmesin in the treatment of AD,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed to provide further research direction.The cognitive function of AD model mice was evaluated by Morris water maze,open field test and new object recognition test.Nissl staining was used to observe the damage of hippocampal neurons.The levels of acetylcholine(Ach),acetylcholine transferase(ChAT),acetylcholinesterase(AChE),reactive oxygen species(ROS),malondialdehyde(MDA)and catalase(CAT)in hippocampus of mice were detected by kit.The protein expression levels of interleukin 6(IL-6),interleukin 1β(IL-1 β),tumor necrosis factor α(TNF-α),nuclear factor E2-related factor 2(NRF2),silent information regulator homologous protein 3(SIRT3),Kelch-like ECH-associated protein 1(KEAP1),quinone oxidoreductase 1(NQO1)and heme oxygenase 1(HO-1)in hippocampus were detected by Western Blot.Results Compared with the model group,the latency of Morris water maze test was significantly shortened in the high-dose marmesin group,the time of entering the target area in the open field new object test and the movement distance in the central area of the open field were prolonged,the number of neurons in the hippocampal CA1 and CA3 regions was significantly increased,the levels of ChAT and Ach in the hippocampus were significantly increased,AChE level was significantly decreased,CAT level was significantly increased,ROS and MDA levels were significantly decreased,TNF-α expression level was decreased,SIRT3 and HO-1 expression levels were increased,and KE AP1 protein expression level was decreased,the differences being statistically significant(P＜0.05 or P＜0.01 or P＜0.001).Conclusion Marmesin can effectively improve the learning and memory impairment of AD mice,and its mechanism may be related to the activation of NRF2/SIRT3 signaling pathway,thereby alleviating oxidative stress level and neuroinflammation,and repairing cholinergic neuron function.