Objective To explore the risk factors and construct a predictive model for the first occurrence of gastrointestinal bleeding in patients with hepatitis B cirrhosis.Methods A total of 142 patients with hepatitis B cirrhosis admitted to the Second Affiliated Hospital of Shandong First Medical University from January 2023 to December 2024 were selected as subjects.Patients with first occurrence of gastrointestinal bleeding were classified as bleeding group(n=52),while patients without such history were devided into no bleeding group(n=90).Baseline data between groups were compared,and potential risk factors for the first occurrence of upper gastrointestinal bleeding in patients with hepatitis B cirrhosis were analyzed.Results Grade C liver function classification,low red blood cell count(RBC),thrombocytopenia,prolonged fibrinogen concentration,serum albumin,prothrombin activity,and prothrombin time,high international standardized ratio,widened main portal vein diameter,and severe esophageal/gastric varices were the risk factors for the first occurrence of gastrointestinal bleeding in patients with hepatitis B cirrhosis(P＜0.05).Multivariate Logistic analysis demonstrated that RBC,portal vein diameter,and severe esophageal/gastric varices were independent risk factors for gastrointestinal bleeding in hepatitis B cirrhosis patients.Conclusion When RBC＜3.25×109/L,portal vein diameter＞14.5 mm and severe esophageal varices are present,the combined diagnosis has a high predictive value for the risk of first upper gastrointestinal bleeding in hepatitis B cirrhosis patients.

Objective To observe the value of multi-sequence magnetic resonance imaging(MRI)radiomics in predicting the efficacy of concurrent chemoradiotherapy(CCRT)in locally advanced cervical squamous cell carcinoma(CSCC)patients.Methods Clinical data of 100 CSCC patients underwent CCRT treatment were selected.In order to better validate the performance of the model,patients were randomly divided into the training set(70 cases)and the validation set(30 cases)in a 7∶3 ratio.According to the efficacy criteria for solid tumors,patients were divided into the complete response(CR)group(n=16)and the partial response(PR)group(n=14).Examination images of cross-sectional DWI,T2WI and enhanced T1WI were collected from all patients before treatment.ITK-SNAP software package combined with three sequences were used to outline ROI,and the open source software PyRadiomics was used to extract image omics features.For MRI omics features,the minimum redundancy maximum correlation(mRMR)algorithm was used to analyze and screen out the first 30 main features,and then the minimum absolute contraction and selection method(Lasso)based on 10-fold cross-validation was used to reduce dimensionality to screen the non-zero coefficient features.According to the weighting coefficient of Lasso-Logistic regression model in the training set,patient omics labels were calculated.Logistic regression analysis was used to construct a prediction model based on DWI,T2WI and T1WI sequence prediction models and multiple sequenomics labels.Receiver operating characteristic(ROC)curves evaluated the predictive value of each omics model for CCRT treatment in patients with locally advanced CSCC.Results There were 38 cases in the CR group and 32 cases in the PR group in the training set.There were 16 cases in the CR group and 14 cases in the PR group in the validation set.There were no significant differences in patient age,FIGO stage,differentiation degree,maximum lesion diameter and menstrual status between the CR group and the PR group in the training and validation sets.A total of 851 imaging features were extracted from the ROI target area.After the first 30 features were retained by mRMR algorithm,3 CR-related features were selected from the 851 imaging omics features of each individual sequence by Lasso algorithm and 10-fold cross-validation.Eight CR related features were selected from 2 553 features after the combination of the three sequences.ROC curve results showed that in the training set and validation set,the AUC of multiple sequences combined to predict the therapeutic effect of CCRT in patients with locally advanced CSCC was 0.971 and 0.946,respectively,which was higher than that of T1WI,T2WI and DWI single sequence prediction(training set Z=2.683,2.046,2.817,P＜0.05;verification set Z=2.075,2.117,2.005,P＜0.05).Conclusion The multi sequence MRI radiomics model has high predictive value for the efficacy of CCRT treatment in locally advanced CSCC patients.

Objective To observe the value of multi-sequence magnetic resonance imaging(MRI)radiomics in predicting the efficacy of concurrent chemoradiotherapy(CCRT)in locally advanced cervical squamous cell carcinoma(CSCC)patients.Methods Clinical data of 100 CSCC patients underwent CCRT treatment were selected.In order to better validate the performance of the model,patients were randomly divided into the training set(70 cases)and the validation set(30 cases)in a 7∶3 ratio.According to the efficacy criteria for solid tumors,patients were divided into the complete response(CR)group(n=16)and the partial response(PR)group(n=14).Examination images of cross-sectional DWI,T2WI and enhanced T1WI were collected from all patients before treatment.ITK-SNAP software package combined with three sequences were used to outline ROI,and the open source software PyRadiomics was used to extract image omics features.For MRI omics features,the minimum redundancy maximum correlation(mRMR)algorithm was used to analyze and screen out the first 30 main features,and then the minimum absolute contraction and selection method(Lasso)based on 10-fold cross-validation was used to reduce dimensionality to screen the non-zero coefficient features.According to the weighting coefficient of Lasso-Logistic regression model in the training set,patient omics labels were calculated.Logistic regression analysis was used to construct a prediction model based on DWI,T2WI and T1WI sequence prediction models and multiple sequenomics labels.Receiver operating characteristic(ROC)curves evaluated the predictive value of each omics model for CCRT treatment in patients with locally advanced CSCC.Results There were 38 cases in the CR group and 32 cases in the PR group in the training set.There were 16 cases in the CR group and 14 cases in the PR group in the validation set.There were no significant differences in patient age,FIGO stage,differentiation degree,maximum lesion diameter and menstrual status between the CR group and the PR group in the training and validation sets.A total of 851 imaging features were extracted from the ROI target area.After the first 30 features were retained by mRMR algorithm,3 CR-related features were selected from the 851 imaging omics features of each individual sequence by Lasso algorithm and 10-fold cross-validation.Eight CR related features were selected from 2 553 features after the combination of the three sequences.ROC curve results showed that in the training set and validation set,the AUC of multiple sequences combined to predict the therapeutic effect of CCRT in patients with locally advanced CSCC was 0.971 and 0.946,respectively,which was higher than that of T1WI,T2WI and DWI single sequence prediction(training set Z=2.683,2.046,2.817,P＜0.05;verification set Z=2.075,2.117,2.005,P＜0.05).Conclusion The multi sequence MRI radiomics model has high predictive value for the efficacy of CCRT treatment in locally advanced CSCC patients.

Objective To explore the risk factors and construct a predictive model for the first occurrence of gastrointestinal bleeding in patients with hepatitis B cirrhosis.Methods A total of 142 patients with hepatitis B cirrhosis admitted to the Second Affiliated Hospital of Shandong First Medical University from January 2023 to December 2024 were selected as subjects.Patients with first occurrence of gastrointestinal bleeding were classified as bleeding group(n=52),while patients without such history were devided into no bleeding group(n=90).Baseline data between groups were compared,and potential risk factors for the first occurrence of upper gastrointestinal bleeding in patients with hepatitis B cirrhosis were analyzed.Results Grade C liver function classification,low red blood cell count(RBC),thrombocytopenia,prolonged fibrinogen concentration,serum albumin,prothrombin activity,and prothrombin time,high international standardized ratio,widened main portal vein diameter,and severe esophageal/gastric varices were the risk factors for the first occurrence of gastrointestinal bleeding in patients with hepatitis B cirrhosis(P＜0.05).Multivariate Logistic analysis demonstrated that RBC,portal vein diameter,and severe esophageal/gastric varices were independent risk factors for gastrointestinal bleeding in hepatitis B cirrhosis patients.Conclusion When RBC＜3.25×109/L,portal vein diameter＞14.5 mm and severe esophageal varices are present,the combined diagnosis has a high predictive value for the risk of first upper gastrointestinal bleeding in hepatitis B cirrhosis patients.

Objective:To investigate the effect of early intervention with electroacupuncture (EA) on the gut microbiota in a mouse model of post-traumatic stress disorder(PTSD).Methods:Totally 32 C57BL/6 mice were randomly assigned to the following 4 groups ( n=8 for each group): Control group, EA group, PTSD group and PTSD+ EA group.After 7 days acclimation, mice in the PTSD group and PTSD+ EA group were subjected to modified single prolonged stress (mSPS). Mice in the EA group and PTSD+ EA group received EA (2/15 Hz, 1 mA, dilatational wave, 30 min/d) on "Baihui" for 7 days. Mice in the Control group and PTSD group received false stimulation (stimulated the same acupiont without electricity) for 7 days. Seven days after the last stimulation, elevated plus maze test and fear conditioning test were conducted to observe the effect of EA on PTSD-like behavior of mice. At the same time, feces of the mice were collected for gut microbiota detection by 16S rRNA sequencing.SPSS 19.0 was used for statistical analysis.One-way ANOVA was used for multiple group comparison and Bonferrani test was done for further pairwise comparision. Results:(1) There were statistically differences in the open arm activity time of the elevated plus maze test and the immobility time in contextual and cued fear conditioning test among the four groups ( F=6.93, 5.26, 14.51, all P<0.01). In the elevated plus maze test, mice in PTSD group ((60.17±15.52) s) showed significant less time in the open arms than mice in Control group((96.37±14.62) s) and PTSD+ EA group ((86.89±15.02) s) (both P<0.05). In the fear conditioning test, mice in PTSD group ((121.99±29.67) s, (130.82±29.11) s) showed significant increased immobility time both in contextual and cued fear conditioning tests than mice in Control group((74.50±26.65) s, (39.50±23.52) s) and PTSD+ EA group ((76.77±22.60) s, (102.17±3.39) s)(both P<0.05). (2) There were no significant differences among the four groups in the alpha diversity of gut microbiota ( F=0.79-2.45, all P>0.05). (3)Correlation analysis showed that 13 gut microbiotas were negatively correlated with the immobility time in contextual fear conditioning test, 2 gut microbiotas were positively correlated with it; 7 gut microbiotas were negatively correlated with the immobility time in cued fear conditioning test, 1 gut microbiota was positively correlated with it; 3 gut microbiotas were positively correlated with time spent in open arms of elevated plus maze test. Conclusion:Early intervention with EA can improve anxiety-fear like behaviors and gut microflora disorder in PTSD model mice.

Objective:To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on the hippocampal lipidome in a rat model of chronic unpredictable stress(CUS).Methods:Twenty-four SD rats were randomly assigned to the following 3 groups ( n=8 for each group): sham group, CUS group and CUS+ rTMS group. The sham group received only sham stimulation and rats in the CUS and CUS+ rTMS group were subjected to CUS stimulation. Then, rats received 5 Hz rTMS (5 Hz, 1.26 Tesla) or sham rTMS for 7 days. After the last stimulation, all rats underwent sucrose preference test, open filed test and forced swimming test so as to observe the effect of rTMS on depressive behavior. Then, rats were sacrificed, and the levels of lipid composition in hippocampus were determined by high performance liquid chromatography mass spectrometry and analyzed by lipid search software version 4.1 and SIMCA-P 14.1.The software of SPSS 19.0 was used for statistical analysis. Univariate analysis of variance was used for comparison among groups, and Tukey test was used for multiple comparison. Results:(1)There were significant differences in open field test, sugar preference test and forced swimming test among the three groups( F=6.853-7.466, all P<0.05). In the open field experiment, the exploring time and percentage of movement distance in central area of rats in CUS group((50.72±6.38)s, (11.41±1.55)%) was significantly less than that of sham group ((86.06±7.31)s, (18.60±1.21)%) and CUS+ rTMS group((79.87±7.87)s, (16.74±1.27)%)(all P<0.05). The results of sucrose preference test showed that the percentage of sucrose intake of rats in CUS group ((37.63±6.06)%) was significantly lower than that in sham group ((68.30±6.39)%) and CUS+ rTMS group ((62.68±5.50)%)(both P<0.05) . In forced swimming test, the immobility time of rats in CUS group ((137.60±13.36)s) was significantly longer than that of sham group ((80.57±10.36)s)) and CUS+ rTMS group ((86.14±11.49)s) (both P<0.05). (2)The levels of lipid composition in hippocampus were significantly different in the three groups( F=3.826-15.440, all P<0.05). The contents of phosphatidylethanolamine (PE) ((20 850±956.56)×10 7, (24 133.33±1 242.04)×10 7), phosphatidylinositol (PI) ((788.78±136.11)×10 7, (953.65±131.26)×10 7), lysophosphatidylcholine (LPC) ((340.29±35.66)×10 7, (275.32±35.78)×10 7), creatine phosphate (CerP) ((239.65±18.14)×10 7, (293.82±38.28)×10 7), sphingosine (So) ((22.96±4.04)×10 7, (15.36±3.87)×10 7), diglyceride (DG) ((3.35±0.85)×10 7, (4.57±1.02)×10 7) and monoglyceride (MG) ((6.71±0.82)×10 7, (7.94±0.91)×10 7)in hippocampus of rats in CUS group were significantly higher than those of sham group(all P<0.05), while the phosphatidic acid(PA) ((424.52±33.38)×10 7, (509.22±42.09)×10 7) and acyl carnitine(AcCa) ((2.68±0.33)×10 7, (3.39±0.33)×10 7) decreased(both P<0.05). Compared with CUS group, the contents of PE(21 816.67±928.26)×10 7, PI(83.16±91.52)×10 7, LPC(323.59±33.91)×10 7, CerP(236.39±32.02)×10 7, So(23.35±4.46)×10 7, DG(3.16±0.85)×10 7 and MG(7.03±0.26)×10 7 in the hippocampus of CuS+ rTMS group decreased, while the contents of PA(421.55±44.28)×10 7 and ACCA(2.56±0.32)×10 7 in the hippocampus of CUS+ rTMS group increased (all P<0.05). Conclusion:The levels of glycerophospholipids, glyceroglycerides, sphingolipids, fatty acids and other lipids in the hippocampus of CUS model rats are abnormal. And the 5 Hz rTMS intervention can ameliorate the depression like behavior and the disturbances of lipid in hippocampus of CUS model rats.

Objective: To explore the association between the single nucleotide polymorphism (SNP) of rs175048 in ataxia telangiectasia mutated (ATM) gene and lung cancer susceptibility in Han population. Methods: A total of 225 cases of blood samples from lung cancer patients treated in Hospital of Traditional Chinese Medicine of Hengyang City and the Affiliated First Hospital of Nanhua University from October 2015 to August 2016 were collected as case group, and 128 cases of blood samples from healthy people were collected as the control. The polymorphisms of ATM rs175048 of above mentioned participants were detected by using the SNP sensitive On/Off Switch technique. The genotypes and allele frequencies were analyzed to compare the distribution difference between case group and control group as well as its association to the clinical features of lung cancer. Results: The genotype frequencies of AA, AT and TT of ATM rs175048 were 24.9%, 52.9%, 22.2% in case group and 42.2%, 42.2%, 15.6% in control group, respectively (all P< 0.01). Moreover, the frequencies of alleles A and T were 51.0%, 49.0% in case group, and 63.0%, 37.0% in control group (all P<0.01). Genotype TT might increase while genotype AT might decrease the risk of lung cancer. rs175048 SNP was significantly correlated with smoking, age, sex and family history (all P<0.05). Conclusion: rs175048 SNPis significantly associated with lung cancer, and TT genotype may increase the risk of lung cancer.

Objective To investigate the antidepressive?like effect of repetitive transcranial magnetic stimulation (rTMS) on the rats model exposing chronic unpredictable stress (CUS) and their nuclearfactor?E2?related factor2 (Nrf2) gene expression in hippocampus. Methods (1) SD rats were randomly assigned to the following 3 groups (n=8 for each group):Sham, CUS, CUS+rTMS. The Sham group received only Sham stimulation. The rats in the CUS and CUMS+ rTMS group were subjected to CUS stimulus, followed by 5Hz rTMS or Sham rTMS for 7 days. 24 h after the last stimulation, rats were given a sucrose preference test, an open filed test and a forced swim test. Finally the gene expression of Nrf2, HO?1 and SOD?1 in the hippocampus were determined by real?time PCR and western blot. (2) SD rats were randomly assigned to another 3 groups (n=8 for each group): scramble+CUS, scramble+ CUS+ rTMS and shNrf2+CUS+rTMS. Rats were injected with scramble or shNf2 lentivirus into the dentate gyrus. Two weeks later, all rats were subjected to CUS followed by rTMS or Sham rTMS stimulus for 7 days. Finally rats were given the series behavior tests, and the gene expression of hippocampal Nrf2, HO?1 and SOD?1 were then determined after being sacrificed. Results (1) In comparison with Sham, the rat in CUS group showed significant lower sucrose preference ((77.31 ± 4.69)％vs. (39.33 ± 11.85)％;F2, 21=8.32, P<0.01) and shorter centre time ((52.49±1.07) s vs. (14.70±4.27) s;F2, 21=3.84, P<0.01)) in the open filed test, but longer freezing time in the forced swim test ((24.19 ± 1.07 s vs. (38.70 ± 4.27);F2, 21=10.31, P<0.05);the expression of Nrf2, HO?1 and SOD?1 in the hippocampus was inhibited in the CUS rats. (2) Compared with CUS group, the rat in CUS+rTMS group showed significant better sucrose preference (P<0.05), longer centre time (P<0.05 in open filed test), while shorter freezing time in the forced swim test (P<0.05); the expression of Nrf2, HO?1 and SOD?1 in the hippocampus in CUS+rTMS rats was up?regulated (P<0.05);(3) Rats in shNrf2+CUS+rTMS group showed lower sucrose preference (P<0.05), shorter centre time (P<0.05) in the open filed test and longer freezing time in the forced swim test (P<0.05) and their expression of Nrf2, HO?1 and SOD?1 in the hippocampus (P<0.05) was down?regulated than rats in scramble+CUS+rTMS group. Conclusion rTMS administration may reverse depressive?like behaviors in rats under CUS paradigm and may restore the gene expression of Nrf2, HO?1 and SOD?1 in the hippocampus.

Objective To investigate the antidepressive?like effect of repetitive transcranial magnetic stimulation (rTMS) on the rats model exposing chronic unpredictable stress (CUS) and their nuclearfactor?E2?related factor2 (Nrf2) gene expression in hippocampus. Methods (1) SD rats were randomly assigned to the following 3 groups (n=8 for each group):Sham, CUS, CUS+rTMS. The Sham group received only Sham stimulation. The rats in the CUS and CUMS+ rTMS group were subjected to CUS stimulus, followed by 5Hz rTMS or Sham rTMS for 7 days. 24 h after the last stimulation, rats were given a sucrose preference test, an open filed test and a forced swim test. Finally the gene expression of Nrf2, HO?1 and SOD?1 in the hippocampus were determined by real?time PCR and western blot. (2) SD rats were randomly assigned to another 3 groups (n=8 for each group): scramble+CUS, scramble+ CUS+ rTMS and shNrf2+CUS+rTMS. Rats were injected with scramble or shNf2 lentivirus into the dentate gyrus. Two weeks later, all rats were subjected to CUS followed by rTMS or Sham rTMS stimulus for 7 days. Finally rats were given the series behavior tests, and the gene expression of hippocampal Nrf2, HO?1 and SOD?1 were then determined after being sacrificed. Results (1) In comparison with Sham, the rat in CUS group showed significant lower sucrose preference ((77.31 ± 4.69)％vs. (39.33 ± 11.85)％;F2, 21=8.32, P<0.01) and shorter centre time ((52.49±1.07) s vs. (14.70±4.27) s;F2, 21=3.84, P<0.01)) in the open filed test, but longer freezing time in the forced swim test ((24.19 ± 1.07 s vs. (38.70 ± 4.27);F2, 21=10.31, P<0.05);the expression of Nrf2, HO?1 and SOD?1 in the hippocampus was inhibited in the CUS rats. (2) Compared with CUS group, the rat in CUS+rTMS group showed significant better sucrose preference (P<0.05), longer centre time (P<0.05 in open filed test), while shorter freezing time in the forced swim test (P<0.05); the expression of Nrf2, HO?1 and SOD?1 in the hippocampus in CUS+rTMS rats was up?regulated (P<0.05);(3) Rats in shNrf2+CUS+rTMS group showed lower sucrose preference (P<0.05), shorter centre time (P<0.05) in the open filed test and longer freezing time in the forced swim test (P<0.05) and their expression of Nrf2, HO?1 and SOD?1 in the hippocampus (P<0.05) was down?regulated than rats in scramble+CUS+rTMS group. Conclusion rTMS administration may reverse depressive?like behaviors in rats under CUS paradigm and may restore the gene expression of Nrf2, HO?1 and SOD?1 in the hippocampus.

Objective To construct mutant recombinant vector of epidermal growth factor receptor ( EGFR) gene G719S and T790M sites associated with cervical cancer, lay the foundation for the detection of EGFR gene mutation in cervical cancer. And using it to es-tablish a molecular switch platform to detect cervical cancer EGFR gene mutations. Methods Using the wild-type recombinant plasmid as template, the mutant fusion target fragment were amplified by overlap PCR, then connect this target fragment into the vector pMD19-T. The constructed mutant recombinant plasmid was finally transformed into competent cells E.coli DH5αfurther identified by PCR with bacterial solution and genome sequencing. Establishing the molecular switch for the detection of clinical cervical cancer samples. Re-sults The G719S and T790M mutations were successfully certified by genome sequencing, and the site-directed mutant vector was successfully constructed. In addition, a molecular switch detection platform was also successfully established for the detection of cervical cancer tissue DNA. Conclusion We successfully constructed an EGFR gene mutant recombinant vector by overlap PCR technique, which providing a new technical means for gene site-directed mutagenesis. And the molecular switch detection platform was successfully established based on it, which furnishing a new method for clinical detection of EGFR gene mutations.