ObjectiveTo investigate the intervention effects of modified Linggui Zhugan Tang （LGZGT） on patients with obstructive sleep apnea-hypopnea syndrome （OSAHS） of the spleen deficiency and dampness obstruction with blood stasis type， reveal its possible mechanisms， and provide a theoretical basis for the clinical treatment of OSAHS with traditional Chinese medicine （TCM）. MethodsEighty OSAHS patients with spleen deficiency and dampness obstruction with blood stasis were randomly assigned to a control group and an observation group （1∶1） using a random number table， with 40 patients in each group. The control group received standard basic treatment combined with oral Doxofylline tablets， while the observation group received standard basic treatment combined with modified LGZGT. Serum levels of macrophage migration inhibitory factor （MIF）， microRNA-223 （miR-223）， and interleukin-18 （IL-18） were measured by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of MIF， miR-223， and IL-18 were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. After two months of treatment， the total clinical efficacy， apnea-hypopnea index （AHI）， lowest nocturnal oxygen saturation （LSpO₂）， body mass index （BMI）， TCM syndrome scores， and expression levels of MIF， miR-223， and IL-18 before and after treatment were compared between the two groups. Correlations between MIF， miR-223， IL-18 and AHI and LSpO₂ were also analyzed. ResultsCompared with the control group， the observation group showed a significantly higher total clinical effective rate （P<0.01， Z=-3.49）. Within the control group， no significant changes were observed in AHI， LSpO₂， BMI， TCM syndrome scores， or MIF， miR-223， IL-18 levels and their mRNAs after treatment. In the observation group， AHI， BMI， TCM syndrome scores， and MIF and IL-18 levels and their mRNAs decreased significantly， while LSpO₂ increased significantly （P<0.01）. After treatment， compared with the control group， the observation group exhibited significantly lower AHI， BMI， TCM syndrome scores， and MIF and IL-18 levels and their mRNAs， and significantly higher LSpO₂ （P<0.01）. Correlation analysis showed that MIF and IL-18 were positively correlated with AHI （P<0.01） and negatively correlated with LSpO₂ （P<0.01）， whereas miR-223 was negatively correlated with AHI （P<0.01） and positively correlated with LSpO₂ （P<0.01）. ConclusionModified LGZGT may improve OSAHS of the spleen deficiency and dampness obstruction with blood stasis type by reducing airway inflammatory factors， alleviating airway inflammation， relieving airway edema and stenosis， and improving airway obstruction.

ObjectiveTo observe the short-term and long-term efficacy of traditional Chinese medicine （TCM） surgical operations in treating mixed hemorrhoids. MethodsA multi-center retrospective cohort study was conducted， collecting clinical data from 17，831 mixed hemorrhoid surgery patients in 8 top-tier TCM hospitals in Jiangsu Province. Standardized and structured datasets were obtained through artificial intelligence models. Patients who underwent western surgical treatment were categorized into the western surgery group （11,646 cases）， and those receiving TCM surgical operations were categorized into the TCM surgery group （6185 cases）. Propensity score matching （1∶1 matching） was used to balance baseline data between groups. The primary outcome was the one-year recurrence rate， and secondary outcomes included the main symptoms （rectal bleeding， degree of prolapse） and secondary symptoms （anal distension， anal edema， wound secretion and exudation， anal stenosis， residual skin tags， perianal itching， and anal pain） measured on days 7， 28， and 60 after discharge. ResultsAfter matching， 2194 patients were included in each group. Symptom scores showed that at 28 days after discharge， the TCM surgical group had superior improvement in rectal bleeding ［OR=5.786， 95%CI （3.092，10.827）］， degree of prolapse ［OR=4.510， 95%CI （1.649，12.333）］， and anal edema ［OR=3.188， 95%CI （1.295，7.845）］ compared to the western surgical group. At 60 days post-discharge， the TCM group still showed advantages in improving rectal bleeding ［OR=5.237， 95%CI （1.077，25.464）］ and anal pain ［OR=11.697， 95%CI （1.186，115.336）］ （P＜0.05）. Long-term follow-up showed that the one-year recurrence rate in the TCM surgery group was 1.1% （8/726）， while that in the western surgery group was 2.3% （10/444）， with no statistically significant difference between the two groups （P＞0.05）. ConclusionBased on real-world data， TCM surgical treatment for mixed hemorrhoids shows significant short-term symptom improvement， particularly in terms of hemostasis， reducing swelling， and alleviating prolapse of anal masses.

Objective To explore the relationship between bedtime procrastination and fear of missing out and the intervention effect of aerobic exercise on bedtime procrastination,so as to provide a theoretical basis and practical reference for remedying bedtime procrastination.Methods Totally 988 students were selected through random sampling and then surveyed with the bedtime procrastination scale and the fear of missing out scale.Correlation and regression analyses were performed to explore the relationship between bedtime procrastination and fear of missing out.A total of 36 students were recruited from the 988 students to participate in the exercise intervention and they were assigned into an exercise group and a control group by the random number table method,with 18 students in each group.The exercise group performed aerobic exercise for 12 weeks,while the control group maintained daily activities.The participants' scores on the bedtime procrastination scale and the fear of missing out scale were recorded before and after the intervention and compared.Results The fear of missing out was positively correlated with bedtime procrastination among college students(r=0.214,P<0.001),and it was an important predictive factor for bedtime procrastination(β=0.241,P<0.001).After the intervention,the scores of bedtime procrastination scale decreased in the exercise group(t=2.277,P=0.036),while there was no significant difference in the scores of the control group before and after intervention(t=-0.787,P=0.442).Conclusions A high level of fear of missing out indicates severe bedtime procrastination.And 12-week exercise intervention could remedy bedtime procrastination.
Humans ; Fear ; Exercise ; Male ; Female ; Procrastination ; Young Adult ; Cross-Sectional Studies ; Students/psychology* ; Adult ; Surveys and Questionnaires ; Adolescent

ObjectiveTo investigate the current status of emergency management for severe mental disorders in Shanghai, and to provide countermeasures and suggestions for the establishment of a sound emergency management system for severe mental disorders and the enhancement of emergency management capability. MethodsA questionnaire survey and qualitative interviews were used to conduct an investigation into the emergency management in 17 district-level mental illness prevention and control institutions in Shanghai, which includes the basic situation of emergency management for severe mental disorders, the construction of emergency response teams and personnel, emergency preparedness drills and training, emergency management plans and rules and regulations, and problems encountered in emergency management. ResultsIn terms of emergency management mechanism and basic situation, resources such as personnel allocation, security funds and green channel were well equipped in each district-level mental illness prevention and control institution in Shanghai. However, the equipment of some hardware facilities was still insufficient to some extent. Therefore, further improvement on the emergency management mechanism for severe mental disorders was needed. With regard to the construction of emergency team and personnel allocation, the majority were those aged between 35‒<45 years old, with a bachelor’s degree, and more than 10 years of working experience. For example, 90.27% staff in district-level mental illness prevention and control institution had a bachelor’s degree or above, which was higher than that among the staff in community-level (73.60%); staff majored in clinical medicine in district-level institution accounted for the proportion at 52.71%, higher than that among the staff in community-level (28.86%); 57.24% staff in district-level institution had an intermediate professional title, higher than that among the staff in community-level (42.28%); and 69.90% staff in district-level institution had more than 10 years of working experience, higher than that among the staff in community-level (43.62%). In the aspect of emergency drills and training, all district-level mental illness prevention and control institutions in Shanghai had a high demand for emergency training, and the weak aspects mainly focused on lack of emergency service protocols, skills of addressing technical challenges, and construction of effectiveness evaluation system. Moreover, the teaching methods were primarily centered on case analysis, simulation drills, interactive discussions, and so forth. Concerning emergency management plans and rules and regulations, all districts in Shanghai had relatively established well-developed systems for emergency response plans, emergency response leadership groups, and emergency response operational task forces for severe mental disorders. About half of the institutions had established other rules and regulations related to emergency management of severe mental disorders in addition to emergency plans. ConclusionShanghai has initially established an emergency management system for severe mental disorders, but it is still fragile in specialized training for emergency management of severe mental disorders, construction of emergency management mechanisms, and the building-up of grassroots emergency teams. Further priorities should include strengthening emergency management training, enhancing the construction of emergency management personnel teams, and gradually establishing a more comprehensive and integrated emergency management mechanism for severe mental disorders.

This research investigated the contamination level,distribution of drug-resistant strains,and molecular epidemiologi-cal characteristics of Campylobacter,and further explored transmission pathways and prevention strategies.Cecum,chicken carcass,chicken product,and environmental samples,as well as swabs from workers'hands,were collected from a slaughterhouse in a large broiler group in the Jiaodong area between August 2023 and July 2024.Quantitative contamination assessment of Campylobacter in chicken carcasses and chicken products was performed.After microbial mass spectrometry identification,the representative strains of different links were selected for drug resistance testing and whole genome sequencing(WGS).On the basis of the sequencing results,the resistance genes,virulence genes,multilocus sequence typing(MLST),and phylogenetic characteristics of representative strains were analyzed.Homology comparisons were performed between isolates and strains from patients with diarrhea in the NCBI database.A total of 297 Campylobacter strains were isolated from 806 samples,and the overall detection rate was 36.85%.The detection rate of Campylobacter was highest in the evisceration process(47.33%),followed by the cutting process(35.64%).Overall,the Campylo-bacter detection rate first increased,then decreased,and subsequently increased.Drug sensitivity testing revealed that 90 isolates were resistant to nalidixic acid and ciprofloxacin,and 94.97%of isolates were resistant to tetracycline.WGS showed that both Campylo-bacter jejuni(C.jejuni)and Campylobacter coli(C.coli)carried many drug resistance and virulence genes.ST-14176 of C.jejuni was isolated for the first time herein.The predominant ST-8261 strain of C.jejuni and ST-860,ST-829,and ST-1586 strains of C.coli are known to cause human diarrhea.LOS expression genes associated with Guillain-Barré syndrome(GBS)were detected in both C.jejuni isolates from the slaughter chain and patients with GBS.Some strains exhibited close genetic relatedness to human-derived Campylo-bacter strains from the NCBI database.The detection rate of Campylobacter in the slaughterhouse first increased,then decreased,and subsequently increased,and the quantitative contamination level of each link was similar to the detection rate.Quantitative analysis of chicken carcasses/products revealed that the average bacterial load was highest in eviscerated carcasses(102.80 cfu/g),and the high-est amount of Campylobacter in chicken products reached 451.80 cfu/g.Abundant drug resistance genes and virulence genes were iden-tified,and the drug resistance genes were highly correlated with the drug resistance rate.Therefore,surveillance intensity and control measures for Campylobacter in slaughter processes should be strengthened.

Objective To establish a ultra-high performance liquid chromatography-tandem mass spectrometer(UPLC-MS/MS)method for determining the concentration of sotagliflozin in rat plasma and apply it to pharmacokinetic studies in rats.Methods Electrospray negative ion multi-reaction ion detection was used.Chromatographic column:EXT-C18(2.1 mm × 100.0 mm,2.7 μm);column temperature:45 ℃;mobile phase:5 mmol·L-1 ammonium acetate aqueous solution-acetonitrile;flow rate:0.35 mL·min-1;ion pairs:sotagliflozin m/z 483.3→315.1,dapagliflozin m/z 467.4→329.2;injection volume:6 μL,plasma samples were processed using methyl tert-butyl ether liquid-liquid extraction.Six male SD rats were administered a single oral dose of sogliflozin at 40 mg·kg-1,and detected the concentration of sogliflozin in plasma.Pharmacokinetic parameters were calculated using Drug And Statistics(DAS)2.1.1.Results Sotagliflozin showed good linearity within the range of 5-2 000 ng·mL-1,with intra-day and inter-day precision both less than 15％.The recovery rate,matrix effect,and stability were all within the specified range.Pharmacokinetic parameters:Cmax was(3 716.67±568.28)ng·mL-1,tmax was(1.00±0.32)h,t1/2 was(2.28±0.45)h,AUC0-t was(1.70 × 104±2 075.87)ng·mL-1·h.Conclusion This study established a method for determining the concentration of sotagliflozin in rat plasma,which is characterized by high sensitivity,rapid detection,and good repeatability.It is suitable for the determination of sotagliflozin concentration in plasma and pharmacokinetic studies.

Objective:To construct a machine learning model based on localization CT-based radiomics, dosiomics and clinical features for predicting radiotherapy response in non-small cell lung cancer (NSCLC) and validate its application value.Methods:A retrospective case series study was conducted. A total of 138 NSCLC patients who received radiotherapy at the Affiliated Hospital of Jining Medical University from January 2016 to December 2022 were selected. The efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, and the patients were stratified according to the objective remission (complete remission+partial remission). Random stratified sampling was used to divide the 138 patients into a training group (96 cases) and an internal validation group (42 cases) at a ratio of 7∶3. Additionally, 33 patients who received radiotherapy at Jining Cancer Hospital from January 2019 to December 2022 were included as the external validation group. Based on the pre-radiotherapy data of the radiotherapy planning system, PyRadiomics software package was used to extract 107 radiomics features and 107 dosiomics features for each patient. Pearson correlation analysis and LASSO regression analysis were used for dimensionality reduction screening; the final selected features were weighted and integrated to generate radiomics-dosiomics scores (RDS), which were then input into logistic regression (LR), support vector machine (SVM), extremely randomized forest (Extra Trees), K-nearest neighbor algorithm (KNN), lightweight gradient boosting machine (Light GBM), and multi-layer perceptron (MLP) machine learning algorithms to construct 6 radiomics-dosiomics models (RDM) for predicting the objective remission. RECIST 1.1 standard was used to evaluate objective remission as the gold standard, receiver operating characteristic (ROC) curve of 6 RDM for predicting objective remission was plotted, and the optimal algorithm for RDM was selected. Univariate and multivariate logistic regression were performed on demographic characteristics, hematological indicators and radiotherapy parameters of the training group to screen independent risk factors for NSCLC patients who received radiotherapy but did not achieve objective remission. These factors were input into the optimal machine learning algorithm to construct a clinical model (CM). Combined with features from RDS and CM, the clinical feature-radiomics-dosiomics combined model (CRDM) was established, and the nomogram of the model for predicting objective remission in NSCLC patients with radiotherapy was drawn. ROC curves were used to evaluate the efficacy of CM, RDM and CRDM in predicting the objective remission in NSCLC patients with radiotherapy in the training group, internal validation group and external validation group.Results:Four radiomics features (including grayscale variance, low grayscale long-range operation emphasis, low grayscale area emphasis, and small area low grayscale area emphasis, all of which were texture features) and 6 dosiomics features [including 1 first-order feature (robust mean absolute deviation), 4 texture features (grayscale non-uniformity, large area emphasis, large area high grayscale emphasis, contrast) and 1 shape feature (shortest axis length)] were selected. ROC curve analysis showed that the area under the curve (AUC) of the RDM constructed using SVM algorithm for judging the objective remission in the training group and the internal validation group was 0.907 (95% CI: 0.836-0.977) and 0.822 (95% CI: 0.685-0.959), which were higher than RDM constructed using other algorithms, and the sensitivity (96.2% and 91.7%), specificity (78.6% and 76.7%) and accuracy (83.3% and 81.0%) at the optimal cut-off values were all higher. Considering the stability and generalization ability of the model, SVM algorithm was ultimately used to construct RDM, CM and CRDM uniformly. Based on training group data, univariate and multivariate logistic regression analysis showed that elevated platelet-to-lymphocyte ratio (PLR) ( OR = 1.001, 95% CI: 1.000-1.003, P = 0.035) and increased target volume of radiotherapy plan ( OR = 1.001, 95% CI: 1.000-1.001, P = 0.008) were independent risk factors for failure to achieve objective remission. ROC curve analysis showed that in the training group and the internal validation group, the AUC of CRDM predicting objective remission were 0.914 (95% CI: 0.856-0.972) and 0.864 (95% CI: 0.754-0.974), respectively, which were better than CM [AUC were 0.735 (95% CI: 0.612-0.857) and 0.697 (95% CI: 0.507-0.888)] and RDM, respectively. In the external validation group, the AUC of CRDM, CM and RDM were 0.778 (95% CI: 0.500-1.000), 0.667 (95% CI: 0.434-0.899) and 0.741 (95% CI: 0.463-1.000), respectively. Conclusions:The CRDM constructed by combining radiomics, dosiomics and clinical features can comprehensively and accurately evaluate the radiotherapy response of NSCLC patients, and may have important clinical application value in achieving precision medicine and optimizing treatment strategies.

Objective To explore the molecular mechanism by which SOS Ras/Rac guanine nucleotide exchange factor 1-intronic transcript 1(SOS1-IT1)affects enhancer of zeste homolog 2(EZH2)protein expression in endometrial cancer cells Ishikawa and RL95-2.Methods Lentiviral transfection of short hairpin RNA(shRNA)and overexpression plasmid were used in Ishikawa and RL95-2 cell lines to knock down and overexpress SOS1-IT1.The mechanism of EZH2 expression regulation was studied using Real-time PCR,Western blotting,and chromatin immunoprecipitation.Results The expression of SOS1-IT1 and EZH2 genes was positively correlated in endometrial cancer tissues.Knocking down SOS1-IT1 significantly reduces the expression of EZH2,inhibited the proliferation and migration of Ishikawa and RL95-2 cells,and could reduced the acetylation of histone H3 at position 27(H3K27)and the enrichment of CREB binding protein(CBP)in the EZH2 gene promoter region.Overexpression of SOS1-IT1 could increased the expression of EZH2 and enhance the acetylation of H3K27 and the enrichment of CBP.CBP could bind to SOS1-IT1 RNA,and this binding ability was weakened when CBP was knocked down.Conclusion SOS1-IT1 can promote the expression level of EZH2 in endometrial cancer cells Ishikawa and RL95-2 by regulating the acetylation modification level of the EZH2 gene promoter region,thereby affecting the proliferation and migration ability of endometrial cancer cells.

Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.