Background::Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.Methods::In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort.Results::In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone.Conclusion::ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.Trial Registration::Chictr.org.cn: ChiCTR2200059599.

Hepatocellular carcinoma(HCC)is one of the most common tumor types and remains a major clinical challenge.Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC.However,few mitophagy inhibitors have been approved for clinical use in humans.Pyrimethamine(Pyr)is used to treat infections caused by protozoan parasites.Recent studies have reported that Pyr may be beneficial in the treatment of various tumors.However,its mechanism of action is still not clearly defined.Here,we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis.Mechanistically,Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells.In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29(SNAP29)-vesicle-associated membrane protein 8(VAMP8)interaction.Moreover,Pyr acted synergistically with sorafenib(Sora)to induce apoptosis and inhibit HCC proliferation in vitro and in vivo.Pyr enhances the sensitivity of HCC cells to Sora,a common chemotherapeutic,by inhibiting mitophagy.Thus,these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor.Notably,Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

ObjectiveTo explore the impact of Gegen Qinliantang（GQT） on the fecal short-chain fatty acids（SCFAs） metabolism in antibiotic-associated diarrhea（AAD） through targeted metabolomics. MethodA total of 240 SD rats were randomly divided into six groups（n=40， half male and half female）， including blank group， model group， bifidobiogen group（0.15 g·kg^-1）， and GQT high-， medium-， and low-dose groups（10.08， 5.04， 2.52 g·kg^-1）， except for the blank group， clindamycin（250 mg·kg^-1） was given to all groups by gavage for modeling every day for 7 d. After successful modeling， each administered group was gavaged with the corresponding dose of the drug， and the blank and model groups were gavaged with an equal volume of normal saline solution， 1 time/d， for 14 d. At 0， 3， 7， 14 d after the drug intervention， eight rats were randomly selected from each group， respectively. Gas chromatography-time-of-flight mass spectrometry（GC-TOF-MS） was used to perform targeted metabolomic analysis of SCFAs in the feces of rats， and partial least squares-discriminant analysis（PLS-DA） was applied to compare the differences in metabolic profiles between groups at different treatment times， and to compare the changes in the contents of SCFAs in rat feces between groups. ResultPLS-DA results showed that the blank group could be clearly distinguishable from the model group， with GQT exhibiting a closer proximity to the blank group after 7 d of treatment. After further analyzing the composition of SCFAs， it was found that the proportion of acetic acid increased and the proportions of butyric acid， valeric acid， hexanoic acid and isovaleric acid decreased in the model group compared with the blank group. After the treatment with GQT， the proportions of butyric acid， isobutyric acid， valeric acid， and isovaleric acid increased， and the proportions of acetic acid， propionic acid and caproic acid decreased. Subsequent differential analysis revealed that GQT could significantly improve the content of butyric acid， and had a certain retrogressive effect on the contents of valeric acid and hexanoic acid. ConclusionThe medium dose group of GQT can improve the contents of SCFAs in AAD feces after 7 days of treatment， which may be related to the improvement of the composition ratio of SCFAs and the contents of butyric acid， valeric acid and caproic acid.

Animals ; Macaca mulatta ; Optic Disk ; Glaucoma ; Craniocerebral Trauma ; Intraocular Pressure ; Low Tension Glaucoma

Objective: The aim of the present study was to develop the beverage addiction scale for college students,so as to provide an effective tool for assessing college students beverage addiction. Methods: In November 2022, a cluster sample of 8 792 college students from three colleges in Yunnan and Jiangxi were surveyed by Beverage Addication Scale for College Students. After a through literature review, 12 items were proposed, including withdrawal symptoms, health effects and addiction symptoms, with 4 items each. The ttest and correlation analysis were used to filter the items, and exploratory factor analysis and confirmatory factor analysis were used to evaluate the structural validity of the questionnaire. In May 2023, 5 279 college students from the above three universities were surveyed again to evaluate the reliability and validity of the scale and the positive demarcation value of symptoms. Results: The scale fitted into a tool for measuring symptoms of beverage dependence in a college student population. The scale was composed of 11 items in accordance with withdrawal symptoms, health effects and addiction symptoms, with a cumulative contribution rate of variance was 74.51%. Cronbach α coefficients for the overall scale and three dimensions were 0.94, 0.88, 0.90 and 0.92, respectively. The correlation coefficient between each item and the total score ranged from 0.56 to 0.79, and the correlation coefficient with the dimension ranged from 0.71 to 0.92. The confirmatory factor analysis model was well fitted, and the RMSEA, CFI, TLI and SRMR value were 0.06, 0.95, 0.93 and 0.04, respectively. The application of the scale showed that scores on the scale and each dimension ≥P85 were positive for symptoms. Conclusion The reliability and validity of Beverage Addiction Scale for College Students is good, which can be used to evaluate the beverage addiction symptom of college students.

Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Objective To explore the mediating role of sleep quality on the impact of occupational stress on depressive symptom among secondary industry occupational population. Methods A total of 895 secondary industry workers in Wuxi City were selected as the study subjects using the stratified random sampling method. The Core Occupational Stress Scale (COSS), Patient Health Questionnaire-9 items (PHQ-9) and Self-Filled Sleep Questionnaire (SSQ) were used to investigate their occupational stress, depressive symptom and sleep quality. Depressive symptom, occupational stress and sleep quality were respectively regarded as dependent variable, independent variable and mediating variable. Process program was used to construct a mediation model, and Bootstrap method was used to test its mediating effect. Results The median score and 25th, 75th percentile for occupational stress, depressive symptom and sleep quality was 43.0 (43.0, 48.0), 6.0 (3.0, 8.0) and 3.0 (1.0, 3.0) points. The detection rates of occupational stress, depressive symptom, sleep disorder were 28.7%, 63.0% and 38.8%, respectively. Spearman correlation analysis result showed that occupational stress was positively correlated with both depressive symptom and sleep quality (Spearman correlation coefficients of 0.46 and 0.49, all P<0.01). Bootstrap test result showed that occupational stress had positive effect on both depressive symptom and sleep quality (partial regression coefficients of 0.25 and 0.09, all P<0.01). Sleep quality partially mediated the impact of occupational stress on depressive symptom with the mediation effect value of 0.05 (95% confidence interval of 0.03-0.06), accounting for 20.0% of the total effect. Conclusion Both depression symptom and sleep quality are positively correlated with occupational stress in secondary industry occupational population. Sleep quality of this population partially mediate the impact of occupational stress on depressive symptom.

The peeled stems of Syringa pinnatifolia(SP) is a representative Mongolian folk medicine with the effects of anti-depression, heat clearance, pain relief, and respiration improvement. It has been clinically used for the treatment of coronary heart disease, insomnia, asthma, and other cardiopulmonary diseases. As part of the systematic study on pharmacological substances of SP, 11 new sesquiterpenoids were isolated from the terpene-containing fractions of the ethanol extract of SP by liquid chromatography-mass spectrometry(LC-MS) and proton nuclear magnetic resonance(~1H-NMR) guided isolation methods. The planar structures of the sesquiterpenoids were identified by MS, 1D NMR, and 2D NMR data analysis, and were named pinnatanoids C and D(1 and 2), and alashanoids T-ZI(3-11), respectively. The structure types of the sesquiterpenoids included pinnatane, humulane, seco-humulane, guaiane, carryophyllane, seco-erimolphane, isodaucane, and other types. However, limited to the low content of compounds, the existence of multiple chiral centers, the flexibility of the structure, or lack of ultraviolet absorption, the stereoscopic configuration remained unresolved. The discovery of various sesquiterpenoids enriches the understanding of the chemical composition of the genus and species and provides references for further analysis of pharmacological substances of SP.
Syringa ; Sesquiterpenes ; Terpenes ; Asthma ; Chromatography, Liquid

Objective:To investigate the efficacy of oblique lumbar interbody fusion (OLIF) combined with percutaneous transforaminal endoscopic decompression (PTED) and posterior pedicle fixation through Wiltse approach in the treatment of lumbar spondylolisthesis accompanied with lumbar spinal stenosis.Methods:From June 2017 to February 2022, 103 patients (50 males and 53 females) of lumbar spondylolisthesis accompanied with lumbar spinal stenosis were performed with OLIF combined with PTED and posterior pedicle fixation. The mean age was 64.1±5.2 years (range, 42-87 years). All involved cases were single-segment and included 83 cases of L 4, 5, 17 cases of L 3, 4, and 3 cases of L 2, 3. Among them, 94 cases were performed for the first time, and other 9 were revision surgery treated by posterior lumbar laminectomy previously. The visual analog scale (VAS) was used to evaluate the low back pain and leg pain, and the Oswestry disability index (ODI) was used to evaluate the lumbar function. The VAS and ODI scores were recorded respectively before the operation, at discharge, 1, 3, 6 months after the operation and at the last follow-up. Macnab criteria was used to evaluate the clinical efficacy at the last follow-up. At the same time, imaging measurements were conducted, including the anterior and posterior disc height, segmental lordotic angle, percentage of slip on lateral X-ray film and the vertebral canal area on axial MRI before and after surgery. Results:All of 103 patients were successfully operated in one stage with an average operation time of 177.7±21.5 min (range, 155-220 min), and an average intraoperative blood loss of 55.9±18.3 ml (range, 30-150 ml). The mean follow-up time were 15.1±2.6 months (range, 6-36 months). There were significant differences in both VAS scores of back and leg and ODI scores at each postoperative time point when compared with preoperative ( F=508.25, F=1524.82, F=1148.68, P<0.001). Macnab criteria of the last follow-up was evaluated as follow: excellent in 85 cases, good in 14, fair in 4, and the excellent and good rate was 96.1%. The radiographic results showed the mean immediate postoperative anterior disc height, posterior disc height, segmental lordotic angle, percentage of slip and axial area of the vertebral canal were 15.23±2.97 mm, 9.32±2.31 mm, 14.36°±4.18°, 3.89%±3.11%, 113.37±47.27 mm 2, and thus all of those increased significantly compared to the mean preoperative 11.93±3.17 mm, 7.21±2.03 mm, 6.15°±3.99°, 23.66%±7.79%, 57.63±28.91 mm 2, respectively ( t=7.84, t=7.07, t=14.91, t=27.62, t=9.68, P<0.001). All cases achieved bony fusion during 6-12 months after operation. The incidence of surgery-related complications was 10.7% (11/103). There were 3 cases of end plate fracture and 2 cases of dural injury, which had no complaint after operation. There was 1 case of pedicle screw entering into the spinal canal by mistake, and the symptoms of nerve damage appeared after operation. After 1 year it basically returned to normal. There were 2 cases of thigh numbness and 1 case of psoas major weakness after operation, all of which relieved after 4 weeks. There was 1 case continuous pain of abdominal incision after surgery. There was 1 case of cage subsidence at the last follow-up. Conclusion:OLIF combined with PTED and posterior pedicle fixation through Wiltse approach is a minimally invasive surgical method for the treatment of lumbar spondylolisthesis accompanied with lumbar spinal stenosis. With the combined minimally invasive techniques, the decompression, fusion and fixation of the lumbar spine can be fulfilled perfectly. It has the advantages of minimally invasive, good clical outcome, few complications and rapid rehabilitation.

ObjectiveTo investigate the mechanism of Gegen Qinliantang（GQT） on the intestinal flora of antibiotic-associated diarrhea（AAD） by 16S rRNA sequencing and network pharmacology. MethodSixty SD rats were randomly divided into six groups（n=10）， including blank group， model group， GQT high-， medium- and low-dose groups（10.08， 5.04， 2.52 g·kg^-1） as well as Lizhu Changle group（0.15 g·kg^-1）， except for the blank group， each group was given clindamycin（250 mg·kg^-1） by gavage once a day for 7 consecutive days. After successful modeling， the blank group and the model group were given equal volumes of normal saline by gavage. The other groups were given corresponding doses of drugs by gavage for 14 days. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） was used to screen the active components and targets of GQT， GeneCards， Online Mendelian Inheritance in Man（OMIM） database， Pharmacogenetics and Pharmacogenomics Knowledge Base（PharmGKB）， DrugBank and DisGeNET were used to search for AAD disease targets. The drug-disease common targets were obtained by R software. STRING was applied to analyze the target protein-protein interaction， and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis was performed. Then hematoxylin-eosin（HE） staining was used to observe the pathological changes of the colon， and 16S rRNA sequencing of AAD colon content flora structure further verified the results of network pharmacology. ResultThrough network pharmacology， it was found that 238 active components were screened from GQT and acted on 276 component targets， among which quercetin， puerarin， wogonin and apigenin were the main core components of GQT， 1 097 AAD disease targets and 127 drug-disease intersection targets. The protein-protein interaction network mainly included core targets such as protein kinase B1（Akt1）， interleukin（IL）-6 and IL-1β， which were mainly enriched in the IL-17 signaling pathway. It was verified through animal experiments that compared with the blank group， the colon structure of the model group was seriously abnormal， the intestinal epithelial columnar cells were damaged， the goblet cells were reduced， and a large number of inflammatory cells were infiltrated. Compared with the model group， the colon structure of the GQT high-dose group improved， but there were still abnormalities， the colon structure of GQT medium- and low- dose groups and Lizhu Changle group improved significantly and reached the normal level. GQT could improve the structural diversity of AAD intestinal flora. At the phylum level， the abundance of Firmicutes was increased and the abundance of Bacteroidetes was decreased. At the genus level， the abundance of Lactobacillus was increased， and the abundances of Prevotella and Bacteroides were decreased. Among them， Lactococcus could be used as a biomarker for AAD treatment with GQT， and the prediction of functional metabolism of intestinal flora revealed that GQT could promote acetate and lactate metabolic pathways in the intestine. ConclusionGQT may activate IL-17 signaling pathway by acting on the targets of Akt1 and IL-6 through key components such as quercetin and wogonin， and improve the abundance of Lactococcus in the intestinal tract as well as acetate and lactate metabolic pathways， so as to play a role in repairing the intestinal barrier for the treatment of AAD.