Objective To establish quality evaluation method of Andrographis paniculata standard decoction by UPLC. Methods 21 batches of Andrographis paniculata standard decoctions were prepared according to the standardization method of TCM decoction pieces. The UPLC characteristic chromatograms analysis method was established. With andrographolide as a reference, quantitative analysis of multi-components by single marker （QAMS） was established for new neoandrographolide, 14 deoxyandrographolide and dehydrated andrographolide. The results were compared with the external standard method （ESM） to determine the accuracy of the method. Results Similarity Evaluation System for Chromatographic Fingerprint of TCM （2012 edition） was used to analyze and compare the characteristic chromatograms, and seven common peaks were determined and five were identified including luteolin-7-O-β-D-glucuronide, andrographolide, neoandrographolide, 14-deoxyandrographolide and dehydroandrographolide. The RSDs of content results of each component by QAMS and ESM were all within 3%. Conclusion The determination method was reliable and accurate, which could be used to reflect the intrinsic quality of Andrographis paniculata standard decoction comprehensively and provide the basis for the quality evaluation of Andrographis paniculata formula granules and other preparations.

Objective:To investigate the impact of frailty on post-stroke depression (PSD) in patients with acute ischemic stroke and to identify risk factors for PSD in order to construct a risk prediction model.Methods:A convenience sampling method was used to recruit a total of 450 patients with acute ischemic stroke who were treated in the Department of Neurology at the Affiliated Hospital of Jining Medical University from March 2023 to April 2024. Data were collected using the Edmonton Frail Scale, Hamilton Depression Rating Scale, Barthel Index (Activities of Daily Living, ADL), Pittsburgh Sleep Quality Index, and Morse Fall Scale. Binary logistic regression analysis was performed to explore the impact of frailty on PSD and to identify other risk factors. Based on the results, a predictive model was developed.Results:A total of 450 questionnaires were distributed, with 412 valid responses returned, yielding a valid response rate of 91.56%. The incidence of PSD among the 412 patients was 45.63% (188/412). Binary Logistic regression analysis showed that frailty, sleep disturbance, C-reactive protein (CRP), and ADL score were the influencing factors for PSD in patients with acute ischemic stroke ( P<0.05). These factors were incorporated into the predictive model, and a risk nomogram was constructed. The area under the curve of the model was 0.764 [95% CI (0.716, 0.811) ], indicating good discriminative ability. Internal validation of the nomogram using the Hosmer-Lemeshow goodness-of-fit test showed χ 2=5.883, P=0.66 ( P>0.05), suggesting good calibration of the model. Conclusions:Frailty increases the risk of post-stroke depression in patients with acute ischemic stroke. Sleep disturbance, CRP level, and ADL score are important screening indicators for PSD risk. Targeted assessment and early intervention are recommended to reduce the likelihood of PSD.

Objective To investigate the association between single nucleotide polymorphisms(SNP)rs57095329 and rs6864584 of miR-146a gene and cervical intraepithelial neoplasia(CIN).Methods A total of 96 patients diagnosed with CIN were randomly collected as the CIN group,and 225 healthy individuals examined during the same period were selected as the control group using SPSS software.Genotyping of the above SNP loci was performed using the TaqMan probe method,and their correlation with CIN was analyzed.Results The allele and genotype distribution of rs57095329 showed a statistically significant differences compared to the control group,with the frequency of the allele A in the CIN group significantly lower than that in the control group(P<0.001;OR=0.48,95%CI:0.32～0.70).In the dominant model,individuals carrying the G allele(A/G-G/G)had a significantly increased risk of CIN(P<0.001;OR=2.67,95%CI:1.64～4.37).In contrast,no correlation was found between the rs6864584 and the risk of CIN.Conclusion The A allele of the miR-146a gene at the rs57095329 locus may be a protective factor for CIN.

Objective:To illustrate the clinical modeling and commissioning results of Monte Carlo dose calculation algorithm in RayStation treatment planning system (TPS) for a domestically developed synchrotron-based spot scanning proton therapy system (SAPT-PS-01).Methods:The proton pencil beam model in RayStation required integral depth dose curves, spot profiles and absolute dose as the input beam data. It was not necessary to collect beam parameters with range shifter. The integral depth dose curves of a single spot were measured by an 8 cm parallel ion chamber. A 2-dimensional scintillation detector was used to measure the in-air spot profile at 5 different depths including the isocenter plane. The absolute dose was calibrated by a 0.25 cm parallel ion chamber under the single energy layer irradiation with a field size of 10 cm × 10 cm. After modeling, the results of the beam model and the Monte Carlo dose calculation algorithm were validated from the range, spot profile, point-dose in a spread-out Bragg peak, planar dose in a clinical plan, point dose in an end-to-end test.Results:For the 94 energy layers, the maximum deviation between the calculated and measured range was 0.03 cm. The maximum difference between the calculated and measured in-air spot sigma was 0.015 cm, and the deviation of in-water spot sigma was measured within ±15%. Compared with the measured values, the calculated dose deviation of 138 measured points in the spread-out Bragg peak was within 3%. For the planar dose verification of clinical plans, the TPS-calculated dose distribution of 285 planes agreed well with the measurement with a minimum gamma-passing rate of 90%, and the gamma passing rate of almost 95% of planes were greater than 95%. The point dose measurements for 8 beams in the end-to-end tests under 4 clinical scenarios were within 5%.Conclusions:The acceptable beam model validation results and successful end-to-end test confirm that the Monte Carlo dose calculation algorithm modeling for the synchrotron-based spot scanning proton therapy system is accurate, which is applicable for the design of patient treatment plan.

Objective:To explore the clinical, imaging, and pathological features of glottic squamous cell carcinoma of the larynx and their relationship with prognosis. Methods:A retrospective analysis was conducted on the clinical, imaging, and pathological data of 130 patients with glottic squamous cell carcinoma of the larynx who were treated at the First People's Hospital of Yinchuan and the General Hospital of Ningxia Medical University from January 2018 to March 2023. Imaging examinations （CT and MRI） were used to evaluate the lesion boundary clarity, density, enhancement nature, and enhancement degree. Postoperative pathological examination was used to determine the pathological nature, immunohistochemistry, etc. Statistical methods such as χ² test, Spearman correlation analysis, multivariate logistic regression analysis, and Kaplan-Meier method were used to analyze the data. Results:Among the 130 patients, 127 were male and 3 were female, with an average age of （61.92±9.595） years. There was a correlation between clinical, imaging, and pathological features. Multivariate analysis showed that heterogeneous MRI density （OR=12.414;P=0.019） and squamous cell carcinoma as a subtype were correlated. The initial symptom of non-hoarseness （HR=6.045;P=0.010） and unclear MRI boundary （HR=12.559; P=0.029） were independent risk factors for poor prognosis in patients with glottic squamous cell carcinoma of the larynx. Conclusion:There is a correlation between the clinical, imaging, and pathological features of patients with glottic squamous cell carcinoma of the larynx, and they can affect prognosis. The initial symptom of non-hoarseness and unclear MRI boundary of the tumor are independent risk factors for poor prognosis.
Humans ; Laryngeal Neoplasms/diagnosis* ; Prognosis ; Male ; Female ; Retrospective Studies ; Middle Aged ; Carcinoma, Squamous Cell/diagnosis* ; Magnetic Resonance Imaging ; Glottis/pathology* ; Tomography, X-Ray Computed ; Aged

Targeting T-cell is a strategy to control allogeneic response disorders, such as acute graft-versus-host disease (GVHD) which is an important cause of therapy-failure after allogeneic hematopoietic cell transplants. Free fatty acid receptor-4 (FFAR4) is a regulator of obesity but its role in T-cell and allogeneic reactions is unknown. Here, we found knockout of Ffar4 in donor T-cells in a mouse allograft model increased acute GVHD whereas the natural FFAR4 ligands and the synthetic FFAR4 agonists decreased it. FFAR4 agonist-mediated anti-acute GVHD effects depended on FFAR4-expression in donor T-cells. The FFAR4 agonist CpdA suppressed donor T-cell-mediated alloreaction by activating an aryl hydrocarbon receptor (AhR) pathway. CpdA recruited β-Arrestin2 to FFAR4 which facilitated nuclear translocation of AhR and upregulation of IL-22. The CpdA-mediated anti-acute GVHD effect was absent in mice receiving Ahr-knockout or Il22-knockout T-cells. Recipient-expressing Ffar4 was also important for the anti-acute GVHD effect of CpdA which inhibited activation of antigen presenting cells. Importantly, CpdA decreased acute GVHD in obese mice, an effect also depended on Ffar4-expression in donor T-cells and recipients. Our study shows the immunoregulatory effect of FFAR4 in T-cell, and targeting FFAR4 might be a relative option for controlling allogeneic reactions in obese patients.

Objective To investigate the predictive value of combining polygenic risk score(PRS)with the National Institutes of Health Stroke Scale(NIHSS)socre for the development of deep venous thrombosis(DVT)in patients with ischemic stroke.Methods A total of 150 patients with ischemic stroke who were hos-pitalized in Jilin Provincial People's Hospital from December 2023 to May 2024 were selected as study sub-jects.After excluding patients who did not meet the criteria,139 patients were successfully followed up and di-vided into two groups based on whether DVT occurred.PRS strategy and fluorescence in situ hybridization(FISH)technology were used to detect the mutation of the gene loci associated with the risk of venous throm-boembolism(VTE).Based on these genotype data and the effect size of single nucleotide polymorphism(SNP)loci,the PRS score of patients was calculated through the model formula.The degree of neurological impairment was evaluated by NIHSS score.Receiver operating characteristics(ROC)curve was used to ana-lyze the efficacy of PRS score,NIHSS score and their combination in predicting ischemic stroke with lower limb DVT,and clinical data related to VTE formation were collected.Results There were no statistically sig-nificant differences between the two groups in terms of gender,age,body mass index(BMI),smoking,alcohol consumption,hypertension,diabetes,D-dimer(D-D),total cholesterol(TC),triglycerides(TG),and lipopro-tein(a)[(LP(a)]levels(P＞0.05).The PRS score,NIHSS score,and Barthel index in the DVT group were significantly higher than those in the non-DVT group,and the proportion of patients with bed rest exceeding 72 h and homocysteine(Hcy)levels were also relatively higher,with statistical significance(P＜0.05).Logis-tic regression analysis showed that PRS score＞2.55,NIHSS score ≥-3 and Barthel index＜60 were inde-pendent risk factors for lower limb DVT after ischemic stroke(P＜0.05).ROC curve analysis results showed that the area under the curve(AUC)of PRS score,NIHSS score and combined prediction of ischemic stroke combined with lower limb DVT were 0.655,0.747 and 0.763,respectively,and the AUC of combined predic-tion was higher than that of single prediction(P＜0.05).Conclusion PRS score combined with NIHSS score has good predictive efficacy for ischemic stroke complicated with DVT.

Objective:To illustrate the clinical modeling and commissioning results of Monte Carlo dose calculation algorithm in RayStation treatment planning system (TPS) for a domestically developed synchrotron-based spot scanning proton therapy system (SAPT-PS-01).Methods:The proton pencil beam model in RayStation required integral depth dose curves, spot profiles and absolute dose as the input beam data. It was not necessary to collect beam parameters with range shifter. The integral depth dose curves of a single spot were measured by an 8 cm parallel ion chamber. A 2-dimensional scintillation detector was used to measure the in-air spot profile at 5 different depths including the isocenter plane. The absolute dose was calibrated by a 0.25 cm parallel ion chamber under the single energy layer irradiation with a field size of 10 cm × 10 cm. After modeling, the results of the beam model and the Monte Carlo dose calculation algorithm were validated from the range, spot profile, point-dose in a spread-out Bragg peak, planar dose in a clinical plan, point dose in an end-to-end test.Results:For the 94 energy layers, the maximum deviation between the calculated and measured range was 0.03 cm. The maximum difference between the calculated and measured in-air spot sigma was 0.015 cm, and the deviation of in-water spot sigma was measured within ±15%. Compared with the measured values, the calculated dose deviation of 138 measured points in the spread-out Bragg peak was within 3%. For the planar dose verification of clinical plans, the TPS-calculated dose distribution of 285 planes agreed well with the measurement with a minimum gamma-passing rate of 90%, and the gamma passing rate of almost 95% of planes were greater than 95%. The point dose measurements for 8 beams in the end-to-end tests under 4 clinical scenarios were within 5%.Conclusions:The acceptable beam model validation results and successful end-to-end test confirm that the Monte Carlo dose calculation algorithm modeling for the synchrotron-based spot scanning proton therapy system is accurate, which is applicable for the design of patient treatment plan.

Objective:To investigate the impact of frailty on post-stroke depression (PSD) in patients with acute ischemic stroke and to identify risk factors for PSD in order to construct a risk prediction model.Methods:A convenience sampling method was used to recruit a total of 450 patients with acute ischemic stroke who were treated in the Department of Neurology at the Affiliated Hospital of Jining Medical University from March 2023 to April 2024. Data were collected using the Edmonton Frail Scale, Hamilton Depression Rating Scale, Barthel Index (Activities of Daily Living, ADL), Pittsburgh Sleep Quality Index, and Morse Fall Scale. Binary logistic regression analysis was performed to explore the impact of frailty on PSD and to identify other risk factors. Based on the results, a predictive model was developed.Results:A total of 450 questionnaires were distributed, with 412 valid responses returned, yielding a valid response rate of 91.56%. The incidence of PSD among the 412 patients was 45.63% (188/412). Binary Logistic regression analysis showed that frailty, sleep disturbance, C-reactive protein (CRP), and ADL score were the influencing factors for PSD in patients with acute ischemic stroke ( P<0.05). These factors were incorporated into the predictive model, and a risk nomogram was constructed. The area under the curve of the model was 0.764 [95% CI (0.716, 0.811) ], indicating good discriminative ability. Internal validation of the nomogram using the Hosmer-Lemeshow goodness-of-fit test showed χ 2=5.883, P=0.66 ( P>0.05), suggesting good calibration of the model. Conclusions:Frailty increases the risk of post-stroke depression in patients with acute ischemic stroke. Sleep disturbance, CRP level, and ADL score are important screening indicators for PSD risk. Targeted assessment and early intervention are recommended to reduce the likelihood of PSD.

Objective To investigate the correlation between rs712 and rs7973450 located at the 3'UTR region of the KRAS gene and the risk of cervical cancer(CC)and cervical intraepithelial neoplasia(CIN)in Chinese Han population in Yunnan province.Methods A total of 2405 individuals(461 subjects with CIN,961 subjects with CC and 983 healthy controls)were enrolled.The SNPs were genotyped used TaqMan assay and the correlation of these SNPs with CIN and CC was analyzed.Results The A allele of rs7973450 might be a protective factor for the occurrence of CIN(P = 0.004,OR= 0.651,95%CI 0.487～0.871)and CC(P = 7.00×10-4,OR= 0.667,95%CI 0.529～0.844).There was no significant difference in allelic and genotypic distribution of rs712 among CIN,CC and Control groups(P>0.017).The haplotype assay showed thatrs712A-rs7973450G was associated with increased risk of CIN(P = 4.00×10-4;OR= 1.714,95%CI 1.269～2.314)and CC(P = 3.84×10-5,OR= 1.667,95%CI 1.305～2.131).While haplotype rs712A-rs7973450A was associated with a lower risk of CC(P = 0.012,OR= 0.790,95%CI 0.658～0.950).Conclusion The A allele of rs7973450 in 3'UTR of KRAS gene might be the protective factor for the occurrence of CIN and CC in a Chinese Han population in Yunnan province.