Objective:To analyze the clinical characteristics, treatments and prognoses of carotid artery dissection (CAD).Methods:Nine patients with CAD, admitted to Department of Neurology, Air Force Medical Center of PLA from May 2010 to April 2024, were chosen; the clinical and imaging data, treatments and prognoses (mRS score≤2: good prognosis) of the patients were retrospectively analyzed.Results:(1) Among the 9 patients with CAD, histories of hypertension, diabetes, head and neck trauma, and radiotherapy were noted 3, 2, 4 and 1 patients, respectively; and unclear past history was noted in 1 patient. Carotid ultrasound was performed in 9 patients: slow blood flow of the internal carotid artery with stenosis or occlusion in 7 patients and normal blood flow of the internal carotid artery in 2 patients were noted. MRA in 5 patients showed severe stenosis or subtotal occlusion in the internal carotid artery. DSA in 8 patients showed CAD plus severe stenosis or subtotal occlusion. (2) After ineffective antiplatelet therapy in 3 patients and ineffective anticoagulant therapy in 2 patients, carotid artery stenting (CAS) was performed; direct CAS was given in one patient, and anticoagulant therapy was given in 3 patients. (3) After 3 months of treatment, 9 patients had a good prognosis; carotid ultrasound in 4 patients showed vascular recanalization; MRA re-examination in 3 patients showed vascular recanalization. DSA re-examination in 1 patient showed vascular recanalization; CTA re-examination in 1 patient showed moderate stenosis of the right internal carotid artery.Conclusion:CAD causes are various; CAD should be considered in patients with neck trauma combined with stroke; endovascular treatment should be considered when antiplatelet/anticoagulant therapy are not effective.

Objective To analyze the relationship of total imaging burden score with blood pressure variability(BPV)and cognitive function in elderly patients with cerebral small vessel disease(CSVD).Methods Clinical data of 182 elderly CSVD patients admitted in our hospital from December 2022 to January 2024 were collected and analyzed retrospectively.According to the results of Chinese Guidelines for Diagnosis and Treatment of CSVD-Related Cognitive Dysfunc-tion(2019),Montreal Cognitive Assessment(MoCA)and other tools for their cognitive impair-ment,they were divided into cognitively impaired group(76 cases)and cognitively normal group(106 cases).The total burden score and BPV indicators[24 h systolic blood pressure coefficient of variation(24 h SBPCV),24 h diastolic blood pressure coefficient of variation(24 h DBPCV)]were compared between the two groups.ROC curve was plotted to evaluate the diagnostic value of total burden score,24 h SBPCV and 24 h DBPCV on cognitive impairment in elderly CSVD patients.Multivariate logistic regression analysis was used to identify the risk factors of cognitive impairment in the patients.Based on the MoCA score of the cognitively impaired group,these pa-tients were further assigned into mild and moderate-to-severe cognitive impairment subgroups[with a MoCA score of 18-25(43 cases)and＜18(33 cases),respectively].Then the total burden score,24 h SBPCV and 24 h DBPCV were compared between the two subgroups.Pearson correla-tion coefficient was adopted to evaluate the correlation of severity of cognitive impairment with total burden score,24 h SBPCV and 24 h DBPCV in the elderly CSVD patients.Results The total burden score,24 h SBPCV and 24 h DBPCV were significantly higher in the cognitively impaired group than the cognitively normal group(P＜0.01).ROC curve analysis indicated that total bur-den score(AUC=0.953,95％CI:0.926-0.980,P=0.000),24 h SBPCV(AUC=0.850,95％CI:0.795-0.906,P=0.000)and 24 h DBPCV(AUC=0.761,95％CI:0.690-0.832,P=0.000)had good diagnostic efficiency for cognitive impairment in the elderly CSVD patients,with a cut-off value of 1.5,11.82％,and 8.92％,respectively.Multivariate logistic regression analysis revealed that the above three indicators were risk factors for cognitive impairment in the elderly patients with CSVD(P＜0.05,P＜0.01).Their values were significantly lower in the mild than the moder-ate-to-severe cognitive impairment subgroups(P＜0.01).Pearson correlation analysis displayed that MoCA score was negatively correlated with total burden score,24 h SBPCV and 24 h DBPCV in elderly patients with CSVD(r=-0.755,-0.632,-0.601,P＜0.01).Conclusion Detection of total burden score and BPV indicators is beneficial to the assessment of cognitive impairment in elderly CSVD patients.The higher the total burden score and the greater the BPV indicators,the more severe the cognitive impairment is,which may explore new ideas for clinical diagnosis and treatment of CSVD.

Objective To analyze the relationship of total imaging burden score with blood pressure variability(BPV)and cognitive function in elderly patients with cerebral small vessel disease(CSVD).Methods Clinical data of 182 elderly CSVD patients admitted in our hospital from December 2022 to January 2024 were collected and analyzed retrospectively.According to the results of Chinese Guidelines for Diagnosis and Treatment of CSVD-Related Cognitive Dysfunc-tion(2019),Montreal Cognitive Assessment(MoCA)and other tools for their cognitive impair-ment,they were divided into cognitively impaired group(76 cases)and cognitively normal group(106 cases).The total burden score and BPV indicators[24 h systolic blood pressure coefficient of variation(24 h SBPCV),24 h diastolic blood pressure coefficient of variation(24 h DBPCV)]were compared between the two groups.ROC curve was plotted to evaluate the diagnostic value of total burden score,24 h SBPCV and 24 h DBPCV on cognitive impairment in elderly CSVD patients.Multivariate logistic regression analysis was used to identify the risk factors of cognitive impairment in the patients.Based on the MoCA score of the cognitively impaired group,these pa-tients were further assigned into mild and moderate-to-severe cognitive impairment subgroups[with a MoCA score of 18-25(43 cases)and＜18(33 cases),respectively].Then the total burden score,24 h SBPCV and 24 h DBPCV were compared between the two subgroups.Pearson correla-tion coefficient was adopted to evaluate the correlation of severity of cognitive impairment with total burden score,24 h SBPCV and 24 h DBPCV in the elderly CSVD patients.Results The total burden score,24 h SBPCV and 24 h DBPCV were significantly higher in the cognitively impaired group than the cognitively normal group(P＜0.01).ROC curve analysis indicated that total bur-den score(AUC=0.953,95％CI:0.926-0.980,P=0.000),24 h SBPCV(AUC=0.850,95％CI:0.795-0.906,P=0.000)and 24 h DBPCV(AUC=0.761,95％CI:0.690-0.832,P=0.000)had good diagnostic efficiency for cognitive impairment in the elderly CSVD patients,with a cut-off value of 1.5,11.82％,and 8.92％,respectively.Multivariate logistic regression analysis revealed that the above three indicators were risk factors for cognitive impairment in the elderly patients with CSVD(P＜0.05,P＜0.01).Their values were significantly lower in the mild than the moder-ate-to-severe cognitive impairment subgroups(P＜0.01).Pearson correlation analysis displayed that MoCA score was negatively correlated with total burden score,24 h SBPCV and 24 h DBPCV in elderly patients with CSVD(r=-0.755,-0.632,-0.601,P＜0.01).Conclusion Detection of total burden score and BPV indicators is beneficial to the assessment of cognitive impairment in elderly CSVD patients.The higher the total burden score and the greater the BPV indicators,the more severe the cognitive impairment is,which may explore new ideas for clinical diagnosis and treatment of CSVD.

Objective:To analyze the clinical characteristics, treatments and prognoses of carotid artery dissection (CAD).Methods:Nine patients with CAD, admitted to Department of Neurology, Air Force Medical Center of PLA from May 2010 to April 2024, were chosen; the clinical and imaging data, treatments and prognoses (mRS score≤2: good prognosis) of the patients were retrospectively analyzed.Results:(1) Among the 9 patients with CAD, histories of hypertension, diabetes, head and neck trauma, and radiotherapy were noted 3, 2, 4 and 1 patients, respectively; and unclear past history was noted in 1 patient. Carotid ultrasound was performed in 9 patients: slow blood flow of the internal carotid artery with stenosis or occlusion in 7 patients and normal blood flow of the internal carotid artery in 2 patients were noted. MRA in 5 patients showed severe stenosis or subtotal occlusion in the internal carotid artery. DSA in 8 patients showed CAD plus severe stenosis or subtotal occlusion. (2) After ineffective antiplatelet therapy in 3 patients and ineffective anticoagulant therapy in 2 patients, carotid artery stenting (CAS) was performed; direct CAS was given in one patient, and anticoagulant therapy was given in 3 patients. (3) After 3 months of treatment, 9 patients had a good prognosis; carotid ultrasound in 4 patients showed vascular recanalization; MRA re-examination in 3 patients showed vascular recanalization. DSA re-examination in 1 patient showed vascular recanalization; CTA re-examination in 1 patient showed moderate stenosis of the right internal carotid artery.Conclusion:CAD causes are various; CAD should be considered in patients with neck trauma combined with stroke; endovascular treatment should be considered when antiplatelet/anticoagulant therapy are not effective.

Interleukin-10（IL-10）is an important anti-inflammatory cytokine in human body，which is mainly secreted by macrophages，Th1 cells and Treg cells.It can inhibit pro-inflammatory mediators，promote anti-inflammatory mediators，inhibit antigen presentation，inhibit immune cell development and promote repair by binding to IL-10 receptors.In recent years，the incidence of IL-10 receptor mutation-related inflammatory bowel disease（IBD）gradually have increased.It shows a younger trend，and the clinical manifestations are not typical，the effect of traditional treatment is not good，which affect the diagnosis and treatment of the disease，as well as the prognosis.This article describes the IL-10 axis and its immune function in IBD，the epidemiology，clinical characteristics and treatment of inflammatory bowel disease related to IL-10 receptor mutation.

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

Tumor-associated tertiary lymphoid structures(TLSs)are ectopic lymphoid formations within tumor tissue,with mainly B and T cell populations forming the organic aggregates.The presence of TLSs in tumors has been strongly associated with patient responsiveness to immunotherapy regimens and improving tumor prognosis.Researchers have been motivated to actively explore TLSs due to their bright clinical application prospects.Various studies have attempted to decipher TLSs regarding their formation mechanism,structural composition,induction generation,predictive markers,and clinical utilization.Meanwhile,the scientific approaches to qualitative and quantitative descriptions are crucial for TLS studies.In terms of detection,hematoxylin and eosin(H&E),multiplex immunohistochemistry(mIHC),multiplex immunofluorescence(mIF),and 12-chemokine gene signature have been the top approved methods.However,no standard methods exist for the quantitative analysis of TLSs,such as absolute TLS count,analysis of TLS constituent cells,structural features,TLS spatial location,density,and maturity.This study reviews the latest research progress on TLS detection and quantification,proposes new directions for TLS assessment,and addresses issues for the quantitative application of TLSs in the clinic.

AIM: To observe the clinical efficacy of Fuzheng Xiaoliu Granules in the treatment of stage II primary liver cancer and to explore its mechanism of action from the perspective of metabolomics. METHODS: Sixty patients with stage II primary liver cancer who achieved complete remission (CR) after comprehensive interventional therapy were randomly divided into treatment group and placebo group, with 30 patients in each group. They were treated for one year and observed for one year. The one-year recurrence rate, traditional chinese medicine (TCM) syndrome score, alpha-fetoprotein and child-pugh grade were compared between the two groups. The serum metabolites of the two groups before and after treatment were screened by ultra-high liquid chromatography-mass spectrometry technology, and the metabolic pathways and related biological pathways were analyzed. RESULTS: The one-year recurrence rate of the treatment group was significantly lower than that of the placebo group, and the overall improvement rate of TCM syndrome score was significantly better than that of the placebo group (P<0.05). There was no statistical significance in the comparison of alpha-fetoprotein and child-pugh grade between the two groups after treatment (P>0.05). Metabolomics results showed that there were 39 and 33 different metabolites in the treatment group before and after treatment and in the two groups after treatment, respectively. After enrichment analysis and topological analysis of the different metabolites, it was found that Fuzheng Xiaoliu Granules could affect amino acid metabolism, fatty acid metabolism and purine metabolism and other metabolic pathways. Before and after treatment in the treatment group and after treatment in the two groups, there were the same differential metabolites and metabolic pathways in the two comparison results. The same differential metabolites with FOLD CHANGE>1 include Stearic acid, Hypoxanthine, Kynurenic acid, Arachidonic acid, and N-Arachidonoyl Dopamine. The same metabolic pathways with Impact>0.1 include Arachidonic acid metabolism and Histidine metabolism. CONCLUSION: Fuzheng xiaoliu granules can effectively reduce the recurrence rate of stage II liver cancer patients after comprehensive intervention and improve the TCM syndrome. It may inhibit the activation of PI3K/Akt and ERK signaling pathways by regulating the content of metabolites involved in metabolic pathways such as amino acids and fatty acids, thereby delaying tumor recurrence.

As one of the hallmarks of cancer, metabolic reprogramming leads to cancer progression, and targeting glycolytic enzymes could be useful strategies for cancer therapy. By screening a small molecule library consisting of 1320 FDA-approved drugs, we found that penfluridol, an antipsychotic drug used to treat schizophrenia, could inhibit glycolysis and induce apoptosis in esophageal squamous cell carcinoma (ESCC). Gene profiling and Ingenuity Pathway Analysis suggested the important role of AMPK in action mechanism of penfluridol. By using drug affinity responsive target stability (DARTS) technology and proteomics, we identified phosphofructokinase, liver type (PFKL), a key enzyme in glycolysis, as a direct target of penfluridol. Penfluridol could not exhibit its anticancer property in PFKL-deficient cancer cells, illustrating that PFKL is essential for the bioactivity of penfluridol. High PFKL expression is correlated with advanced stages and poor survival of ESCC patients, and silencing of PFKL significantly suppressed tumor growth. Mechanistically, direct binding of penfluridol and PFKL inhibits glucose consumption, lactate and ATP production, leads to nuclear translocation of FOXO3a and subsequent transcriptional activation of BIM in an AMPK-dependent manner. Taken together, PFKL is a potential prognostic biomarker and therapeutic target in ESCC, and penfluridol may be a new therapeutic option for management of this lethal disease.

Objective:To investigate the characteristics and change law of influenza in Fuling District of Chongqing in 2010-2019, and to provide a scientific basis for the pre-control of influenza.Methods:We performed an epidemiological analysis on the data of influenza-like illness reported by Fuling District influenza surveillance sentinel hospitals in Chongqing in 2010-2019.Results:In 2010-2019, a total of 42 169 cases of influenza-like illness were reported in Fuling District, with an average treatment rate of 1.22%. The activity of influenza-like illness peaked in winter, spring, and summer. There were 22 788 cases in the group of cases aged < 5 years, accounting for 50.4%. In 2010-2019, a total of 8049 pharyngeal swabs were collected to screen for influenza-like illness, with a positive rate of 14.52%. Influenza virus A H3 positive rate was highest, accounting for 37.98%, followed by influenza virus B BV positive rate, accounting for 30.80%. The highest influenza virus-positive rate was reported in January (26.34%), followed by November (24.85%).Conclusion:Influenza in the Fuling district of Chongqing mainly occurs in winter, spring, and summer. Influenza virus A H3 is the dominant strain. Children and school students are prone to develop influenza-like illnesses. We should continue to strengthen the monitoring of influenza strains, greatly promote vaccination, and strengthen the monitoring and prevention of influenza-like illness among susceptible populations.