POEMS syndrome is a rare condition associated with plasma cell disorders， and it often involves multiple systems and has diverse clinical manifestations. This article reports two cases of POEMS syndrome with hepatosplenomegaly as the initial manifestation. During the course of the disease， the patients presented with lower limb weakness， hepatosplenomegaly， lymph node enlargement， ascites， hypothyroidism， positive M protein， and skin hyperpigmentation， and ¹⁸F-FDG PET-CT imaging revealed bone lesions mainly characterized by osteolytic changes and plasma cell tumors. There was an increase in the serum level of vascular endothelial growth factor. The patients were finally diagnosed with POEMS syndrome， and the symptoms were relieved after immunomodulatory treatment.

Objective To study the brain functional connectivity(FC)changes in patients with normal tension glau-coma(NTG)and healthy volunteers using FC technique of resting-state functional magnetic resonance imaging(rs-fMRI)based on V1 region seed point(ROI),so as to explore the pathogenesis and early diagnosis of NTG.Methods Fourteen NTG patients(NTG group)who met the inclusion criteria and 14 healthy controls(HCs group)were enrolled.The clinical data of all subjects were collected,and rs-fMRI was performed in both groups.The magnetic resonance data was pre-pro-cessed by software,and bilateral A1 regions were taken as the ROI to analyze their correction with the whole brain voxel time series and obtain the FC value between the ROI and the whole brain by comparison of FC values in resting state be-tween the groups.Pearson correlation analysis was used to explore the relationship between FC value in the brain regions with significant differences with the ROI and clinical variables in the NTG group.Results Compared with the subjects in the HCs group,there were no statistically significant differences in age,gender,body weight,cup-disc ratio and 24 h mean intraocular pressure of patients in the NTG group(all P＞0.05),and there were statistically significant differences in the best corrected visual acuity(BCVA)of both eyes and peripapillary retinal nerve fiber layer thickness(RNFLT)(all P＜0.05).The Pearson correlation analysis showed that FC value of the brain regions with abnormal FC to V1 region were cor-related with RNFLT in the NTG group(P＜0.05).ROI1-left superior frontal gyrus,ROI1-right superior frontal gyrus,ROI2-left cingulate gyrus and ROI2-right middle frontal gyrus were significantly positively correlated with RNFLT(all P＜0.05).Compared with the HCs group,the brain regions with reduced FC to the right ROI in the NTG group were the left superior frontal gyrus and right superior frontal gyrus;the brain regions with reduced FC to the left ROI were the left cingulate gyrus and right middle frontal gyrus.Conclusion Compared to healthy individuals,NTG patients have significant changes in the functional connections between certain specific brain regions and V1 region,including bilateral superior frontal gyrus,left cingulate gyrus,and middle frontal gyrus.The changes in brain functional activity may be caused by visual dysfunction caused by NTG,leading to functional impairment of the visual and cognitive emotion processing brain regions,which may be one of the potential neuropathological mechanisms in NTG patients.

Objective To explore the changes in macular microcirculation status and visual function in patients with normal tension glaucoma(NTG)using the optical coherence tomography angiography(OCTA)and microperimeter MP-3 and analyze the correlation between the two.Methods In this cross-sectional observational study,17 NTG patients(30 eyes)were collected as the NTG group and then divided into mild,moderate and severe NTG subgroups according to the severity of the disease.During the same period,13 healthy subjects(23 eyes)with the same age and gender distribution were selected as the control group.OCTA was used to obtain linear density(LD)and perfusion density(PD)of superficial retinal vessels in the macular area.The microperimeter MP-3 was used to measure retinal sensitivity(RS)within 10° and fixation rate at 2° and 4° of the macular area.The OCTA parameters and microperimeter MP-3 parameters were compared among all groups,and the correlation between OCTA parameters and microperimeter MP-3 parameters in NTG patients was analyzed.Results There were no significant differences in LD and PD between the control group and the mild NTG sub-group in the central and nasal sides of the macula;the LD and PD in the remaining regions and overall average LD and PD showed a gradual downward trend in the control group and the mild,moderate and severe NTG subgroups.Compared with the control group,the RS of the mild NTG subgroup was lower in the inferior and temporal regions of the macular area.The RS of each region and overall average RS in the macular area decreased with the aggravation of the NTG.In the NTG group,LD and PD were significantly positively correlated with RS in each region and overall average RS in the macular area(all P＜0.05).In the NTG group,LD and PD were positively correlated with P2 in some regions of the macular area.Con-clusion Compared with the control group,the macular microcirculation status and visual function of NTG patients signif-icantly decreased with the progression of the disease;there is a significant correlation between macular LD and RS in NTG patients.

Objective:To analyze the genetic variations and clinical phenotypic characteristics of epilepsy associated with CSNK2B gene mutations. Methods:A case series summary study.Clinical data of 15 epileptic children with CSNK2B gene mutations diagnosed and treated at the Third Affiliated Hospital of Zhengzhou University and the Peking University First Hospital from February 2016 to October 2023 were retrospectively analyzed.The clinical manifestations, genotypes, and electroencephalography (EEG) results were summarized. Results:Among the 15 children (8 boys and 7 girls), 14 cases had de novo mutations in the CSNK2B gene, and 1 case had hereditary variations.There were 5 missense variants, 4 splice-site variants, 3 frameshift variants, and 3 nonsense variants.Ten mutation sites had not been previously reported (c.326G>A/p.Cys109Tyr, c.485A>G/p.His162Arg, c.368-1G>A, c.464A>C/p.Asp155Ala, c.301T>G/p.Tyr101Asp, c.342T>A/p.Cys114*, c.198del/p.Asn67Thrfs*5, c.292-10T>G, c.573-574del/p.Lys191Asnfs*54, and c. 11C>G/p.Ser4*).The age of onset of seizures ranged from 14 days to 6 years, with 13 cases starting within 2 years old.The types of seizures included focal seizures in 9 cases, generalized tonic-clonic seizure (GTCS) in 5 cases, myoclonic seizures in 1 case, atonic seizures in 1 case, atypical absence seizures in 1 case, and epileptic seizures in 1 case.Three cases had multiple seizures, and 4 cases had cluster seizures.The EEG showed slow background activity in 1 case.Epileptiform discharges were observed in 13 cases during the interictal phase, including generalized discharges in 6 cases, multifocal discharges in 3 cases, and focal discharges in 5 cases.Two cases had normal EEG findings.Brain magnetic resonance imaging results were normal in 10 cases.The age of the last follow-up ranged from 1 year and 1 month to 13 years and 10 months.Seizures were controlled in 12 cases treated with 1 or 2 antiepileptic drugs, while seizures persisted in 2 cases treated with multiple antiepileptic drugs, and 1 case suffered no seizures for 1 year and 3 months, without antiepileptic drug treatment.Oxcarbazepine was effective in 5 cases (5/7), Valproate sodium was effective in 6 cases (6/8), and Levetiracetam was effective in 3 cases (3/9). Conclusions:CSNK2B gene mutations are mainly de novo mutations, and epilepsy triggered by them typically starts within 2 years of age.GTCS and focal seizures are the most common types.The seizures of most children are easily controlled with the effective treatment of Oxcarbazepine, Valproate sodium, and Levetiracetam.

Objective:To summarize the genotype and clinical phenotype of children with WWOX gene related developmental and epileptic encephalopathy (DEE).Methods:Case series studies. The clinical data of 12 children with WWOX gene related DEE who were admitted to the Neurological Department of Children′s Medical Center, Peking University First Hospital from June 2019 to December 2023 were analyzed. The children′s characteristics of gene variation, clinical phenotype, auxiliary examination results, treatment and prognosis were analyzed.Results:Among 12 children with WWOX gene related DEE, there were 7 boys and 5 girls, the age of seizure onset ranged from 10 days to 6 months (median 1.8 months). Multiple seizure types were observed, including focal seizures in 10 cases, epileptic spasms in 9 cases, tonic seizures in 4 cases, myoclonic seizures in 1 case. Among 12 cases, 9 cases had multiple seizure types. All 12 cases showed microcephaly and global developmental delay. Video electroencephalography showed slowed background activity in 6 cases, hyperarrhythmia in 6 cases, multifocal discharges in 6 cases, and focal discharges in 1 case. Epileptic spasms were detected in 8 cases, tonic seizures in 4 cases and myoclonic seizures in 1 case. Brain magnetic resonance imaging showed bilateral frontotemporal subarachnoid space widening in 5 cases, deep sulci in 3 cases, bilateral ventricular enlargement in 2 cases, callosal hypoplasia in 5 cases, and delayed white matter myelination in 3 cases. The phenotypes of 12 cases were consistent with the diagnosis of DEE, and 8 of them were diagnosed with infantile epileptic spasm syndrome. All the WWOX gene variants in 12 cases were complex heterozygous variants, including 20 variants, 11 variants and 1 large intragenic WWOX gene deletion (p.Ala149Thr, p.Arg156Ser, p.R167Tfs*8, p.Leu186Val, c.605+5G>A, p.Trp218*, p.His263Arg, p.Leu275fs*19*1, p.N285Kfs*10, p.Ser304Tyr, p.Met326Arg, loss1 exon2-8) had not been reported previously. The age of last follow-up ranged from 11 months to 5 years and 3 months. During the follow-up, 1 case died at the age of 1 year and 10 months, 2 cases were seizure-free, and 9 cases still had seizures after multiple anti-seizure medications.Conclusions:The seizure onset age of children with WWOX gene related DEE is usually less than 6 months, and some of them in neonate. The common seizure types include focal seizures and epileptic spasms. Children usually have microcephaly and global developmental delay. WWOX gene related DEE usually has drug refractory epilepsy.

Objective:To summarize the clinical features of epilepsy and (or) developmental delay associated with KCNB1 gene variants in children.Methods:A case series study was conducted on 24 children with KCNB1 gene variants associated with epilepsy and (or) developmental delay who were treated at the Children′s Medical Center of Peking University First Hospital and the Department of Neurology of Shenzhen Children′s Hospital from July 2015 to June 2024. The manifestations of seizures, electroencephalogram (EEG) and genetic test results of those children were analyzed.Results:All the KCNB1 gene variants were de novo, involving 20 different variation, including 15 missense variations, 3 frameshift variations and 2 nonsense variations. There were 7 novel variations. Among the 24 developmental and epileptic encephalopathy children, there were 14 boys and 10 girls. The last follow-up age ranged from 9 months to 13 years and 9 months. Seizures were present in 21 children (88%), with onset ranging from 1 month to 7 years, and 76% (16/21) began before 2 years of age. The seizure types included focal seizures in 15 children (71%), epileptic spasms, myoclonic seizures, and generalized tonic-clonic seizures in 6 children respectively, atypical absence seizures in 4 children, and myoclonic atonic seizures in 1 child. Seventeen children (81%) had a cluster of seizures and 5 had a history of focal status epilepticus with impaired consciousness. All 24 children had varying degrees of developmental delay, with 3 presenting solely developmental delay. EEG abnormalities were present in all the 21 children with seizures, including focal or multifocal discharges in 20 children, generalized discharges in 10 children, hypsarrhythmia in 2 children, and electrical status epilepticus during sleep in 3 children. Magnetic resonance imaging abnormalities were found in 5 of the 24 children. Among the 21 children with seizures, 57% (12/21) achieved seizure control.Conclusions:KCNB1 gene variants are predominantly de novo missense variation. Most affected children present with epilepsy, though some may exhibit only developmental delay. Epilepsy often begins before 2 years of age, with focal seizures being the most common type. About 80% of patients experience clustered seizures. Although most patients achieve seizure control, they still exhibit varying degrees of developmental delay, consistent with developmental epileptic encephalopathy.

Objective:To investigate the application value of a multi-dimensional digital moni-toring platform for perioperative period in gastric cancer patients.Methods:The retrospective cohort study was conducted. The clinical data of 50 patients who underwent laparoscopic radical gastrec-tomy in The Affiliated Hospital of Nanjing University of Chinese Medicine from July 2022 to January 2024 were collected. There were 35 males and 15 females, aged (64±12)years. All patients followed the concept of enhanced recovery after surgery, and the multi-dimensional digital monitoring platform based on wearable monitoring equipment was used to implement perioperative management measures. Observation indicators: (1) results of heart rate variability (HRV) monitoring; (2) results of blood glucose and blood oxygen monitoring; (3) results of exercise and sleep monitoring; (4) results of body composition monitoring. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(IQR). Repeated measurement data were analyzed using the repeated ANOVA. Measurement data with skewed distri-bution were transformed to normal distribution by SPSS transformation function before testing. For comparison between pre- and postoperation, paired sample t test was used for measurement data with normal distribution, and nonparametric Wilcoxon signed rank sum test was used for measure-ment data with skewed distribution. Results:(1) Results of HRV monitoring. From preoperation to the third day after surgery, the standard deviation normal to normal heart beat of 50 patients was changed from(103±26)ms to(101±36)ms, the mean of the standard deviations of normal to normal heart beat calculated per 5 min segment was changed from (45±16)ms to(33±12)ms, the number of pairs of adjacent NN intervals differing by more than 50 ms in the entire recording was changed from 6.02%(4.96%) to 5.79%(4.20%), the low frequency power was changed from 376.78(468.96)ms 2 to 742.79(525.20)ms 2, the high frequency power was changed from 273.61(273.58)ms 2 to 397.48(164.87)ms 2, the ratio of low frequency power to high frequency power was changed from 1.6±0.5 to 1.6±0.6, showing significant differences in above indicators before and after operation ( F=34.43, 26.15, 24.58, 5.51, 6.11, 6.02, P<0.05). (2) Results of blood glucose and blood oxygen monitoring. From preoperation to the third day after surgery, the blood glucose of 50 patients was changed from 6.75(2.05)mmol/L to 6.90(2.63)mmol/L, showng a significant difference before and after operation ( F=45.84, P<0.05). The blood oxygen was changed from 97.00%(5.00%) to 97.50%(3.00%), showing no significant difference before and after operation ( F=2.25, P>0.05). (3) Results of exercise and sleep monitoring. From preoperation to the third day after surgery, the number of steps fo 50 pati-ents was changed from 3 043(1 224) to 1 473(767), sleep duration was changed from(8.2±1.1)hours to(7.3±0.8)hours, sleep score was changed from 80±10 to 78±5,showing significant differences in above indicators before and after operation ( F=716.46, 29.02, 47.32, P<0.05).(4) Results of body composition monitoring. The body weight of 50 patients was changed from (63±8)kg to(61±8)kg before and after operation, body fat rate was changed from 24%±8% to 22%±9%, muscle mass was changed from 43 (12)kg to 41(17)kg, body mass index was changed from (23.0±2.6)kg/m 2 to(22.1±2.5)kg/m 2, showing significant differences in above indicators before and after operation ( t=8.19, 3.00, Z=-2.78, t=7.34, P<0.05), while there was no significant difference in basal metabolic indicators from (1 390±134)kcal to (1 379±139)kcal before and after operation ( t=1.02, P>0.05). Conclusion:The multi-dimensional digital monitoring platform for preoperative period can accurately monitor the perioperative stress level and evaluate the postoperative recovery of gastric cancer patients, which can present the visual results.

Objective:To summarize the clinical phenotypes and genetic variations of children with epilepsy related to CLCN4 gene mutations. Methods:A retrospective analysis was conducted on 9 children with epilepsy who were diagnosed with CLCN4 gene mutations through whole-exome sequencing of family members. These children were treated at the Department of Pediatrics, Peking University First Hospital from December 2016 to March 2024. Their clinical manifestations, electroencephalogram, cranial imaging characteristics, and treatment follow-up were reviewed. Results:Among the 9 children, 6 were male and 3 were female. All cases involved de novo mutations. Three cases carried the c.823G>A/p.V275M variant, 2 cases carried the c.2152C>T/ p.R718W variant, 1 case carried the c.1630G>A/pG544R variant, and 1 case carried the c.2167C>T/ p.R723W variant. Two cases carried the unreported new variant c.848G>T/p.S283I and c.818G>A/ p.G273E. The onset age of epilepsy ranged from 55 days to 10 years, with a median onset age of 14 months. Seven out of 9 children had epilepsy onset before the age of 2 years. The types of seizures varied: 8 had focal seizures, 1 had generalized tonic-clonic seizures, 2 had myoclonic seizures, 1 had epileptic spasms, and 1 had atypical absence seizures. Three children experienced multiple types of seizures. All 9 children exhibited developmental delays to varying degrees: 8 had global developmental delay and 1 had cognitive developmental delay. Developmental delays were observed in 7 children before the onset of epilepsy. Clinically, 1 child was diagnosed with infantile epileptic spasms syndrome, 7 with unclassified developmental and epileptic encephalopathy, and 1 with focal epilepsy with developmental delay. At the last follow-up, the age of the children ranged from 2 years and 5 months to 13 years and 9 months. Seizures had been controlled in 3 children for a duration of 4 to 12 months. Conclusions:De novo variants are common in CLCN4 variants. Most seizures onset in infancy, seizure types are various, and focal seizures are common. Most of them have developmental delay and drug-resistant epilepsy, and some of them have developmental delay before seizure onset, which is consistent with the characteristics of developmental and epileptic encephalopathy.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Fat accumulation "sensitizes" the liver to insult and leads to nonalcoholic steatohepatitis (NASH). G protein-coupled receptor 35 (GPR35) is involved in metabolic stresses, but its role in NAFLD is unknown. We report that hepatocyte GPR35 mitigates NASH by regulating hepatic cholesterol homeostasis. Specifically, we found that GPR35 overexpression in hepatocytes protected against high-fat/cholesterol/fructose (HFCF) diet-induced steatohepatitis, whereas loss of GPR35 had the opposite effect. Administration of the GPR35 agonist kynurenic acid (Kyna) suppressed HFCF diet-induced steatohepatitis in mice. Kyna/GPR35 induced expression of StAR-related lipid transfer protein 4 (STARD4) through the ERK1/2 signaling pathway, ultimately resulting in hepatic cholesterol esterification and bile acid synthesis (BAS). The overexpression of STARD4 increased the expression of the BAS rate-limiting enzymes cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1, promoting the conversion of cholesterol to bile acid. The protective effect induced by GPR35 overexpression in hepatocytes disappeared in hepatocyte STARD4-knockdown mice. STARD4 overexpression in hepatocytes reversed the aggravation of HFCF diet-induced steatohepatitis caused by the loss of GPR35 expression in hepatocytes in mice. Our findings indicate that the GPR35-STARD4 axis is a promising therapeutic target for NAFLD.

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).