ObjectiveThis study aims to investigate the effect of Dictamni Cortex on intestinal barrier damage in rats and its mechanism by untargeted metabolomics and targeted metabolomics for short-chain fatty acids （SCFAs）. MethodsRats were randomly divided into a control group， a high-dose group of Dictamni Cortex （8.1 g·kg^-1）， a medium-dose group （2.7 g·kg^-1）， and a low-dose group （0.9 g·kg^-1）. Except for the control group， the other groups were administered different doses of Dictamni Cortex by gavage for eight consecutive weeks. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in the ileal tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to detect the level of cytokines， including tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）， in the ileal tissue of rats. Quantitative real-time fluorescence polymerase chain reaction （Real-time PCR） technology was used to detect the expression level of tight junction proteins， including zonula occludens-1 （ZO-1）， Occludin， and Claudin-1 mRNAs， in the ileal tissue of rats to preliminarily explore the effects of Dictamni Cortex on intestinal damage. The dose with the most significant toxic phenotype was selected to further reveal the effects of Dictamni Cortex on the metabolic profile of ileal tissue in rats by non-targeted metabolomics combined with targeted metabolomics for SCFAs. ResultsCompared with the control group， all doses of Dictamni Cortex induced varying degrees of pathological damage in the ileum， increased TNF-α （P<0.01）， IL-6 （P<0.01）， and IL-1β （P<0.01） levels in the ileal tissue， and decreased the expression level of ZO-1 （P<0.05， P<0.01）， Occludin （P<0.01）， and Claudin-1 （P<0.05） in the ileal tissue， with the high-dose group showing the most significant toxic phenotypes. The damage mechanisms of the high-dose group of Dictamni Cortex on the ileal tissue were further explored by integrating non-targeted metabolomics and targeted metabolomics for SCFAs. The non-targeted metabolomics results showed that 21 differential metabolites were identified in the control group and the high-dose group. Compared with that in the control group， after Dictamni Cortex intervention， the level of 14 metabolites was significantly increased （P<0.05， P<0.01）， and the level of seven metabolites was significantly decreased （P<0.05， P<0.01） in the ileal contents. These metabolites collectively acted on 10 related metabolic pathways， including glycerophospholipids and primary bile acid biosynthesis. The quantitative data of targeted metabolomics for SCFAs showed that Dictamni Cortex intervention disrupted the level of propionic acid， butyric acid， acetic acid， caproic acid， isobutyric acid， isovaleric acid， valeric acid， and isocaproic acid in the ileal contents of rats. Compared with those in the control group， the level of isobutyric acid， isovaleric acid， and valeric acid were significantly increased， while the level of propionic acid， butyric acid， and acetic acid were significantly decreased in the ileal contents of rats after Dictamni Cortex intervention （P<0.05， P<0.01）. ConclusionDictamni Cortex can induce intestinal damage by regulating glycerophospholipid metabolism， primary bile acid biosynthesis， and metabolic pathways for SCFAs.

Objective:To analyze the etiological characteristics, serotype distribution, drug resistance and molecular typing characteristics based on data collected by active surveillance of foodborne diseases in Shanxi Province from 2021 to 2022.Methods:Fecal and anal swabs for foodborne disease tests were collected from 17 sentinel hospitals in Shanxi Province from 2021 to 2022. The pathogens included Shigella, Salmonella, Vibrio parahaemolyticus and 5 types of diarrheagenic Escherichia coli ( E. coli). The positive strains were identified by mass spectrometry or systematic biochemistry. Salmonella and Shigella were serotyped by slide agglutination, and diarrheagenic E. coli was typed by multiplex fluorescence PCR. Vibrio parahaemolyticus was tested for tlh/ tdh/ trh virulence genes by multiplex fluorescent PCR. All strains were also tested for drug resistance by the microbroth dilution method. Molecular typing was performed by pulsed-field gel electrophoresis (PFGE). Results:A total of 4 481 samples were collected from patients with diarrhea, and 555 target strains were detected, with a detection rate of 12.39%(555/4 481). Among them, there were 365 strains of Salmonella, 175 strains of diarrheagenic E. coli, 15 strains of Vibrio parahaemolyticus, and no Shigella. There were 32 serotypes of Salmonella, and the dominant serotypes were 158 strains of Salmonella senteritidis and 124 strains of Salmonella typhimurium. diarrheagenic E. coli classification: 79 strains of enteroaggregative E. coli, 72 strains of enteropathogenic E. coli, 23 strains of enterotoxic E. coli, 1 strain of enterohemorrhagic E. coli, and none of enteroinvasive E. coli. For Vibrio parahaemolyticus virulence gene carriage, all strains carried tlh; 11 strains (73.33%, 11/15) carried tdh only; 2 strains (13.33%, 2/15) carried trh; 1 strain (6.67%, 1/15) carried both tdh and trh genes; 1 strain (6.67%, 1/15) did not carry these two virulence genes. Antimicrobial resistance tests presented that Salmonella had the highest resistance rate to ampicillin (85.21%, 311/365), followed by naphridic acid (66.58%, 243/365), and multi-drug resistance (78.63%, 287/365), resulting in 135 drug resistance spectrums. The resistance rate of diarrheagenic E. coli to ampicillin was the highest (81.71%, 143/175), followed by tetracycline (67.43%, 118/175), and multi-drug resistance (72.57%, 127/175), resulting in 81 drug resistance spectrums. Vibrio parahaemolyticus had the highest resistance rate to cefazolin (93.33%, 14/15), followed by tetracycline (26.67%, 4/15) and multi-drug resistance (20.00%, 3/15), resulting in 3 drug resistance spectrums. A total of 158 strains of Salmonella enteritidi, 124 strains of Salmonella typhimurium, 13 strains of Salmonella london and 175 strains of DEC were typed by PFGE. Among 470 strains of PFGE typing, 6 strains of DEC were degraded by DNA, while the remaining strains obtained effective PFGE band. Salmonella enteritidi were divided into 64 PFGE band types, Salmonella typhimurium were divided into 115 PFGE band types, Salmonella london were divided into 13 PFGE band types and diarrheagenic E. coli were divided into 165 PFGE band types. Conclusions:Shigella is not detected in the active surveillance, and Salmonella is detected most frequently. Salmonella and diarrheagenic E. coli have the highest resistance rates to ampicillin, and Vibrio parahaemolyticus has the highest resistance rates to cefazolin. The PFGE classification is polymorphic, and the dominant band type is not obvious. The evidence of multi-drug resistance suggests further strengthening monitoring and management of drug resistance.

Objective:To investigate the association between frailty and prognosis of elderly patients in the emergency department, and to validate frailty screening tools suitable for the emergency department.Methods:This was a prospective cohort study. Clinical data of elderly patients over 60 years old treated in the emergency department of Beijing Bo'Ai Hospital from January to December 2021 were collected. The Frailty Screening Questionnaire (FSQ), FRAIL Scale (FRAIL) and Clinical Frailty Scale (CFS) were used to score patients, and patients were divided into frail or non-frail group according to the criteria of the above three scales. Twelve-month all-cause mortality was the primary endpoint, dependence and re-admission to the emergency department within 12 months were secondary outcomes. Receiver operating characteristic curves were used to evaluate the ability of the FSQ, FRAIL and CFS scores to predict the primary and secondary endpoints, and the areas under the curve (AUC) were calculated and compared. Survival analysis was performed using Cox hazard proportional regression model, and relative risk was expressed as hazard ratio ( HR) and 95% CI. Results:A total of 406 patients were included in the study. The AUCs (95% CI) of FSQ, FRAIL and CFS scores for predicting 12-month all-cause mortality were 0.879 (0.844-0.909), 0.838 (0.798-0.872), 0.906 (0.873-0.933), respectively (all P<0.001). The AUCs of 3 scores for predicting secondary endpoints ranged from 0.820 to 0.889 (all P<0.001). Pairwise comparisons of the AUCs showed that the CFS was superior to one or both of the other frailty screening scales in predicting 12-month all-cause mortality and dependence except for re-admission to emergency room within 12 months after discharge (all P<0.05). Cox regression analysis revealed that, after adjusting for sex, age, body mass index and comorbidities, frailty as defined by the FSQ, FRAIL, and CFS scales was independently associated with 12-month all-cause mortality, with the HRadj of 3.267 (95% CI: 2.406-4.435), 2.465 (95% CI: 1.819-3.341), 3.523 (95% CI: 2.648-4.687), respectively (all P<0.001). Conclusions:FSQ, FRAIL and CFS scores can predict adverse outcomes, the CFS is a practical frailty screening tool in the emergency department, and frailty screening can improve the risk stratification of older patients.

A sandglass ladder residual network(SLRN)is proposed for multi-label chest X-ray classification,thereby improving the accuracy of clinical diagnosis.SLRN consists of 3 key modules:(1)a sandglass convolutional module to simultaneously extract inter-channel and spatial information;(2)a ladder self attention block to achieve different window divisions through shift operations,expand the receptive field,and realize multi-scale feature extraction and fusion;(3)class specific residual attention in the multi-label classification stage to capture the correlation between different labels and the importance of features for accomplishing more accurate classification by adjusting the weights of different features.The proposed model is validated using the IU X-Ray dataset collected by Indiana University and the publicly available Chest X-Ray14 dataset collected by the National Institutes of Health in the United States;and the results demonstrate that SLRN which combines the advantages of convolutional neural network and vision transformer enables the capture of local features and global correlations in images,better handles long-distance dependencies,and assists doctors in clinical diagnosis.

A sandglass ladder residual network(SLRN)is proposed for multi-label chest X-ray classification,thereby improving the accuracy of clinical diagnosis.SLRN consists of 3 key modules:(1)a sandglass convolutional module to simultaneously extract inter-channel and spatial information;(2)a ladder self attention block to achieve different window divisions through shift operations,expand the receptive field,and realize multi-scale feature extraction and fusion;(3)class specific residual attention in the multi-label classification stage to capture the correlation between different labels and the importance of features for accomplishing more accurate classification by adjusting the weights of different features.The proposed model is validated using the IU X-Ray dataset collected by Indiana University and the publicly available Chest X-Ray14 dataset collected by the National Institutes of Health in the United States;and the results demonstrate that SLRN which combines the advantages of convolutional neural network and vision transformer enables the capture of local features and global correlations in images,better handles long-distance dependencies,and assists doctors in clinical diagnosis.

Objective:To analyze the etiological characteristics, serotype distribution, drug resistance and molecular typing characteristics based on data collected by active surveillance of foodborne diseases in Shanxi Province from 2021 to 2022.Methods:Fecal and anal swabs for foodborne disease tests were collected from 17 sentinel hospitals in Shanxi Province from 2021 to 2022. The pathogens included Shigella, Salmonella, Vibrio parahaemolyticus and 5 types of diarrheagenic Escherichia coli ( E. coli). The positive strains were identified by mass spectrometry or systematic biochemistry. Salmonella and Shigella were serotyped by slide agglutination, and diarrheagenic E. coli was typed by multiplex fluorescence PCR. Vibrio parahaemolyticus was tested for tlh/ tdh/ trh virulence genes by multiplex fluorescent PCR. All strains were also tested for drug resistance by the microbroth dilution method. Molecular typing was performed by pulsed-field gel electrophoresis (PFGE). Results:A total of 4 481 samples were collected from patients with diarrhea, and 555 target strains were detected, with a detection rate of 12.39%(555/4 481). Among them, there were 365 strains of Salmonella, 175 strains of diarrheagenic E. coli, 15 strains of Vibrio parahaemolyticus, and no Shigella. There were 32 serotypes of Salmonella, and the dominant serotypes were 158 strains of Salmonella senteritidis and 124 strains of Salmonella typhimurium. diarrheagenic E. coli classification: 79 strains of enteroaggregative E. coli, 72 strains of enteropathogenic E. coli, 23 strains of enterotoxic E. coli, 1 strain of enterohemorrhagic E. coli, and none of enteroinvasive E. coli. For Vibrio parahaemolyticus virulence gene carriage, all strains carried tlh; 11 strains (73.33%, 11/15) carried tdh only; 2 strains (13.33%, 2/15) carried trh; 1 strain (6.67%, 1/15) carried both tdh and trh genes; 1 strain (6.67%, 1/15) did not carry these two virulence genes. Antimicrobial resistance tests presented that Salmonella had the highest resistance rate to ampicillin (85.21%, 311/365), followed by naphridic acid (66.58%, 243/365), and multi-drug resistance (78.63%, 287/365), resulting in 135 drug resistance spectrums. The resistance rate of diarrheagenic E. coli to ampicillin was the highest (81.71%, 143/175), followed by tetracycline (67.43%, 118/175), and multi-drug resistance (72.57%, 127/175), resulting in 81 drug resistance spectrums. Vibrio parahaemolyticus had the highest resistance rate to cefazolin (93.33%, 14/15), followed by tetracycline (26.67%, 4/15) and multi-drug resistance (20.00%, 3/15), resulting in 3 drug resistance spectrums. A total of 158 strains of Salmonella enteritidi, 124 strains of Salmonella typhimurium, 13 strains of Salmonella london and 175 strains of DEC were typed by PFGE. Among 470 strains of PFGE typing, 6 strains of DEC were degraded by DNA, while the remaining strains obtained effective PFGE band. Salmonella enteritidi were divided into 64 PFGE band types, Salmonella typhimurium were divided into 115 PFGE band types, Salmonella london were divided into 13 PFGE band types and diarrheagenic E. coli were divided into 165 PFGE band types. Conclusions:Shigella is not detected in the active surveillance, and Salmonella is detected most frequently. Salmonella and diarrheagenic E. coli have the highest resistance rates to ampicillin, and Vibrio parahaemolyticus has the highest resistance rates to cefazolin. The PFGE classification is polymorphic, and the dominant band type is not obvious. The evidence of multi-drug resistance suggests further strengthening monitoring and management of drug resistance.

Objective:To analyze the clinical and pathological data of 15 patients with light chain amyloidosis initially diagnosed with other kidney diseases, and identify possible misdiagnosis reasons.Methods:It was a retrospective observational study. The clinical and pathological data of 15 patients, whose initial kidney biopsies failed to diagnose light chain-amyloidosis but were confirmed by a subsequent kidney biopsy or pathology consultation at Peking University First Hospital from January 2010 to December 2022 were collected. The results of immunofluorescence, Congo red staining, and electron microscopy of two renal biopsies were analyzed.Results:The median age of 15 patients was 56 years old, with a male-to-female ratio of 7∶8. The main clinical manifestation was massive proteinuria with normal kidney function, and there were 10 cases presenting as nephrotic syndrome. The initial diagnosis based on the first kidney biopsy included minimal change disease (8 cases), IgA nephropathy (3 cases), membranous nephropathy (3 cases), and type Ⅲ collagen glomerulonephritis (1 case). M proteinemia was not evaluated in 13 patients during the first kidney biopsy. Light chain immunofluorescence staining was not performed in 12 cases. Congo red staining was not performed in 13 cases. All fifteen patients received glucocorticoids combined with immunosuppressive therapy after their initial diagnosis, and 5 patients developed severe infection. After 12.0 (7.5, 20.0) months of treatment, none of them achieved clinical remission. Thirteen had evidences for M protein before the second kidney biopsy. The renal tissues of all patients underwent immunofluorescence light chain examination, Congo red staining, and immunoelectron microscopy examination when necessary. The repeat kidney biopsies of 14 cases and pathology consultation of one case consistently indicated light chain-amyloidosis. The kidney tissues in 13 cases were confirmed to be light chain restricted, 11 cases by immunofluorescence, and 2 cases by immune electron microscopy. After diagnosis of light chain-amyloidosis, all patients received targeted plasma cell therapy except for 1 patient lost to follow-up, 6 patients achieved hematologic remission, 5 patients achieved renal remission, 1 patient entered end-stage renal disease, and 3 patients died.Conclusions:In middle and elderly-aged patients with nephrotic syndrome, if conventional immunosuppressive therapy yields unsatisfactory results, it is crucial to focus on identifying evidences of monoclonal immunoglobulinemia, if necessary, kidney biopsy should be actively repeated. Kidney biopsy pathology should include comprehensive examinations such as light chain immunofluorescence, Congo red staining, and electron microscopy to avoid misdiagnosis of light chain-amyloidosis.

The correlations of global/local properties of brain networks with gambling behavioral scales in depression are explored.The task-state brain functional magnetic resonance imaging data of 24 patients with gambling behavior and depression and 24 healthy controls are analyzed,and preprocessed by SPM software.Graph theory analysis method is used to establish the functional brain networks in which local and global properties are calculated.Two sets of local attribute index including node degree and node efficiency are used to make edge analysis in different depression groups(major,moderate and mild depression groups,with 8 patients in each group)and healthy control group,and the changes in global properties are also discussed.Additionally,the correlations of scoring scale related to gambling behavior with 3 criteria on the global properties(small world attribute,global efficiency and local efficiency)are analyzed.The two-sample t-tests on depression groups and healthy control group confirm the significant connections among brain regions(P＜0.05),and reveal the significant negative correlations between the global brain network attribute indexes and different behavioral scales,which fully verifies the correlation between gambling behavior and depression,and provides the basis for further exploring correlation between the individual behavior attribute and depression,thereby assisting clinical diagnosis and treatment of depression patients.

Objective:To compare the characteristics of corneal stromal demarcation line after different surgical methods of riboflavin/ultraviolet A corneal collagen cross-linking (CXL) in early keratoconus, and analyze the influence of the demarcation line on the cross-linking effect.Methods:A non-randomized controlled clinical study was conducted.Sixty-nine eyes of 69 patients treated with riboflavin/ultraviolet A CXL in the Eye Hospital of Shandong First Medical University from May 2019 to February 2021 were included.According to the cross-linking methods, the patients were divided into epithelium-on treatment group (21 eyes) and epithelium-off treatment group (48 eyes). There were 25 eyes in 5.4 J energy group and 44 eyes in 7.2 J energy group.The morphology and changes of corneal stromal cross-linking reaction (corneal stromal demarcation line) were observed at 2 weeks, 1, 3 and 4 months after operation.Changes in the thinnest corneal thickness (TCT), uncorrected visual acuity (UCVA, LogMAR), best corrected visual acuity (BCVA, LogMAR) and corneal maximum curvature (Kmax) were recorded.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Eye Hospital of Shandong First Medical University (No.2019.05). Written informed consent was obtained from each subject.Results:Of the 69 eyes after operation, 44 eyes (63.77%) had demarcation lines, and 25 eyes (36.23%) had no demarcation lines.The occurrence rate of demarcation lines in the epithelium-on treatment group was 79.17%(38/48), which was significantly higher than 28.57%(6/21) in the epithelium-off treatment group ( χ2=16.186, P<0.01). The occurrence rate of demarcation line in 5.4 J energy group was 72.00%(18/25), and the 7.2 J energy group was 56.80%(25/44), with no significant difference ( χ2=1.565, P=0.302). Slit lamp microscopy and anterior segment-optical coherence tomography showed that the demarcation line appeared at 1-2 weeks after operation, gradually converged and strengthened after 1 month, turned diffuse, blurred and faded by degrees after 2-3 months, and basically disappeared after 4 months.The depth of the demarcation line reached 141-423 μm, with an average depth of (263.44±84.22)μm.Scanning laser confocal microscopy showed that corneal stromal cells were activated and light reflection was enhanced after CXL.Collagen fibers extended vertically and horizontally, crisscrossed, and were in a reticular arrangement.The TCT decreased from preoperative (458.69±38.28)μm to (443.86±36.54)μm at 4 months after operation, showing a statistically significant difference ( t=6.705, P<0.001). There was no significant difference in the TCT reduction between groups with and without demarcation lines ( t=1.684, P=0.100). At 4 months postoperatively, the UCVA of all eyes increased from preoperative 0.74±0.37 to 0.69±0.38, and the difference was statistically significant ( t=2.109, P=0.039). There was no significant difference in BCVA between before and after operation ( t=1.006, P=0.319). There was no significant difference in change of UCVA and BCVA between groups with and without demarcation lines ( t=0.065, P=0.949; t=0.346, P=0.730). There was no significant difference in Kmax in all patients between before and after operation ( t=0.050, P=0.950). There was no significant difference in the Kmax change between groups with and without demarcation lines ( t=-0.739, P=0.464). The change in TCT in the epithelium-off treatment group was significantly greater than that in the epithelium-on treatment group ( t=2.815, P=0.008). There was no significant difference in UCVA, BCVA and Kmax changes between epithelium-on and epithelium-off treatment groups (all at P>0.05). There was no obvious corneal scarring, infectious keratitis, corneal endothelial decompensation or other complications. Conclusions:The demarcation line after CXL may be a sign of the depth of cross-linking reaction, which is more prone to occur after the epithelium-off operation method.Both the epithelium-on and epithelium-off operation methods have similar therapeutic effects.Demarcation line after different cross-linking methods has no significant influence on the cross-linking effect in keratoconus.