Objective:To investigate the efficacy and potential mechanism of sulfasalazine (SASP) therapy for intrahepatic cholestasis.Methods:Forty SD rats were randomly divided into a normal group (carboxymethylcellulose sodium 0.5%), a model group (carboxymethylcellulose sodium 0.5%), a SASP group (sulfasalazine 150 mg/kg), and an ursodeoxycholic acid (UDCA 100 mg/kg) group, with ten rats in each group. The cholestatic liver injury model was induced using α-naphthylisothiocyanate. Blood samples were collected to detect liver biochemistry and cholestasis indexes. Rat liver tissue was collected for hematoxylin-eosin staining and Mason staining. Liver tissue was analyzed using transcriptome sequencing, real-time reverse transcription quantitative polymerase chain reaction, Western blotting and flow cytometry. Simultaneously, the level of inflammatory factors, total cholesterol, and total bile acids were measured in liver tissue. A t-test or a nonparametric test was selected based on the distribution and variance characteristics of the data. Results:The serum levels of alanine aminotransferase [(386.88±155.77) U/L], aspartate aminotransferase [(593.13±251.44) U/L], alkaline phosphatase [(561.25±167.54) U/L], total bilirubin [(38.00±29.75) mol/L] and total bile acids [(191.31±91.48) mol/L] were significantly lower in the SASP than the model groups [(778.75±313.59) U/L, (1 159.38±274.62) U/L, (801.25±161.28) U/L, (86.63±27.83) mol/L, (432.63±151.54) mol/L, P<0.05]. Liver histopathology showed that the inflammatory cells in the manifold area, the bile duct proliferation and dilation, and the collagen deposition in the manifold area were significantly improved under the pathological state of cholestasis in the SASP group. The results of transcriptome sequencing demonstrated that SASP activated the peroxisome proliferator actived receptor α (PPAR α) and inhibited Th17 cell differentiation. The PPARα mRNA level in the liver tissue of rats was significantly increased in the SASP group compared with that in the model group [(0.41±0.28) vs. (0.16±0.04), P<0.05], and the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase was decreased compared with that in the model group [(3.09±1.16) vs. (8.19±2.19), P<0.05], which was also verified at the protein level. The concentrations of total cholesterol [(0.31±0.34) mmol/g] and total bile acids [(2.58±0.99) μmol/g] were lower than the model group [(0.83±0.62) mmol/g and (4.07±0.91) μmol/g] ( P<0.05), and at the same time it was accompanied by lower levels of inflammatory factors ( P<0.05). SASP treatment decreased the expression of retinoic acid receptor-related orphan receptor γt gene ( P<0.05) and the proportion of Th17 ( P<0.05). Conclusion:SASP can improve cholestatic liver injury, and its mechanism is related to the activation of peroxisome proliferator-activated receptor α and the inhibition of Th17 cell differentiation.

Objective To investigate the application value of bronchoalveolar lavage fluid(BALF)met-agenomic next-generation sequencing(mNGS)in elderly patients with severe pneumonia.Methods A total of 48 elderly patients with severe pneumonia admitted to the intensive care unit from January to August 2024 were selected and randomly divided into an observation group and a control group,with 24 patients in each group.BALF samples were collected within 24 hours of ICU admission from both groups,with lavage per-formed at the most radiologically evident lesion site.The control group underwent traditional culture at the hospital,while the observation group had one specimen sent for mNGS testing and another specimen subjected to traditional culture at the hospital.Comparison of detection results between mNGS and traditional culture in the observation group,pathogen distribution,infection markers(on days 4 and 7 of ICU admission),and prog-nostic outcomes were compared between the groups.Results The observation group showed higher positive detection rates and higher rates of detecting ≥2 pathogens by mNGS compared to both traditional culture in the same group and the control group(P＜0.05).Excluding Acinetobacter baumannii,Candida albicans,Can-dida glabrata,and Raoultella planticola,the observation group detected higher quantities of fungi,viruses,and rare pathogens than the control group.On days 4 and 7 of ICU admission,the observation group had signifi-cantly lower body temperature,white blood cell count,C reactive protein,and procalcitonin levels compared to the control group(P＜0.05).The observation group also demonstrated shorter ICU stays,reduced mechanical ventilation duration,and total lower hospitalization costs than the control group(P＜0.05).Conclusion BALF mNGS facilitates early identification of mixed and rare pathogens,improves detection rates,broadens microbial coverage,and shortens testing time.

Objective:To investigate the efficacy and potential mechanism of sulfasalazine (SASP) therapy for intrahepatic cholestasis.Methods:Forty SD rats were randomly divided into a normal group (carboxymethylcellulose sodium 0.5%), a model group (carboxymethylcellulose sodium 0.5%), a SASP group (sulfasalazine 150 mg/kg), and an ursodeoxycholic acid (UDCA 100 mg/kg) group, with ten rats in each group. The cholestatic liver injury model was induced using α-naphthylisothiocyanate. Blood samples were collected to detect liver biochemistry and cholestasis indexes. Rat liver tissue was collected for hematoxylin-eosin staining and Mason staining. Liver tissue was analyzed using transcriptome sequencing, real-time reverse transcription quantitative polymerase chain reaction, Western blotting and flow cytometry. Simultaneously, the level of inflammatory factors, total cholesterol, and total bile acids were measured in liver tissue. A t-test or a nonparametric test was selected based on the distribution and variance characteristics of the data. Results:The serum levels of alanine aminotransferase [(386.88±155.77) U/L], aspartate aminotransferase [(593.13±251.44) U/L], alkaline phosphatase [(561.25±167.54) U/L], total bilirubin [(38.00±29.75) mol/L] and total bile acids [(191.31±91.48) mol/L] were significantly lower in the SASP than the model groups [(778.75±313.59) U/L, (1 159.38±274.62) U/L, (801.25±161.28) U/L, (86.63±27.83) mol/L, (432.63±151.54) mol/L, P<0.05]. Liver histopathology showed that the inflammatory cells in the manifold area, the bile duct proliferation and dilation, and the collagen deposition in the manifold area were significantly improved under the pathological state of cholestasis in the SASP group. The results of transcriptome sequencing demonstrated that SASP activated the peroxisome proliferator actived receptor α (PPAR α) and inhibited Th17 cell differentiation. The PPARα mRNA level in the liver tissue of rats was significantly increased in the SASP group compared with that in the model group [(0.41±0.28) vs. (0.16±0.04), P<0.05], and the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase was decreased compared with that in the model group [(3.09±1.16) vs. (8.19±2.19), P<0.05], which was also verified at the protein level. The concentrations of total cholesterol [(0.31±0.34) mmol/g] and total bile acids [(2.58±0.99) μmol/g] were lower than the model group [(0.83±0.62) mmol/g and (4.07±0.91) μmol/g] ( P<0.05), and at the same time it was accompanied by lower levels of inflammatory factors ( P<0.05). SASP treatment decreased the expression of retinoic acid receptor-related orphan receptor γt gene ( P<0.05) and the proportion of Th17 ( P<0.05). Conclusion:SASP can improve cholestatic liver injury, and its mechanism is related to the activation of peroxisome proliferator-activated receptor α and the inhibition of Th17 cell differentiation.

To provide new ideas for clinical diagnosis and treatment of coronavirus disease 2019 (COVID-19), this study explore the expression level and prognostic value of platelet parameters in mild, moderate and severe COVID-19. This is a retrospective analysis. From January to May 2020, a total of 69 patients who were diagnosed with COVID-19 in the Third Central Hospital and the Jinnan Hospital (both situated in Tianjin) were enrolled in the disease group. According to the severity, these patients were divided into mild group (15 cases), moderate group (46 cases), and severe group (8 cases). In the same period, 70 non-infected patients were enrolled in control group. The level of white blood cell count (WBC), absolute neutrophil count (NEU#), absolute lymphocyte count (LY#), neutrophil-lymphocyte ratio (NLR), red blood cell count (RBC), hemoglobin (Hb), platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and platelet-large contrast ratio (P-LCR) before and after treatment were analyzed. Binary logistic regression analysis is used to establish a mathematical model of the relationship between these indexes and the outcome of severe COVID-19 patients. The receiver operating characteristic(ROC) curve is used to further explore the prognosis value of MPV, P-LCR, NLR separately and jointly in COVID-19 patients. Compare to the control group, WBC and NE# increase ( Z=-5.63, P<0.01; Z=-9.19, P<0.01) and LY# decrease ( Z=-9.34, P<0.01) in the severe group; NLR increase with the aggravation of the disease, there is significant difference between groups ( Z=17.61, P<0.01); PLT, PDW, MPV and P-LCR decrease with the aggravation of the disease, there is significant difference between groups ( Z=9.47, P<0.01; Z=11.41, P<0.01; Z =16.76, P<0.01; Z=13.97, P<0.01). Binary logistic regression analysis shows MPV, P-LCR and NLR have predictive value for severe COVID-19 patients. There is a negative correlation between MPV, P-LCR and severe COVID-19 patients ( OR=1.004, P=0.034; OR=1.097, P=0.046). There is a positive correlation between NLR and severe COVID-19 patients ( OR=1.052, P=0.016). MPV and P-LCR of patients with good prognosis after treatment were significantly higher than those before treatment ( Z=-6.47, P<0.01; Z=-5.36, P<0.01). NLR was significantly lower than that before treatment ( Z=-8.13, P<0.01). MPV and P-LCR in poor prognosis group were significantly lower than those before treatment ( Z=-9.46, P<0.01; Z=-6.81, P<0.01). NLR was significantly higher than that before treatment ( Z=-3.24, P<0.01). There were significant differences between good and poor prognosis groups before and after treatment in MPV, P-LCR and NLR ( P<0.01). Combination of these three indexes, ROC shows the AUC is 0.931, the sensitivity is 91.5%, the specificity is 94.1%, the positive predictive value is 88.9%, and the negative predictive value is 87.4%, which is better than any of these indexes separately. Changes in these parameters are closely related to clinical stage of COVID-19 patients. MPV, P-LCR and NLR are of great value in the prediction and prognosis of severe COVID-19 patients.

To provide new ideas for clinical diagnosis and treatment of coronavirus disease 2019 (COVID-19), this study explore the expression level and prognostic value of platelet parameters in mild, moderate and severe COVID-19. This is a retrospective analysis. From January to May 2020, a total of 69 patients who were diagnosed with COVID-19 in the Third Central Hospital and the Jinnan Hospital (both situated in Tianjin) were enrolled in the disease group. According to the severity, these patients were divided into mild group (15 cases), moderate group (46 cases), and severe group (8 cases). In the same period, 70 non-infected patients were enrolled in control group. The level of white blood cell count (WBC), absolute neutrophil count (NEU#), absolute lymphocyte count (LY#), neutrophil-lymphocyte ratio (NLR), red blood cell count (RBC), hemoglobin (Hb), platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and platelet-large contrast ratio (P-LCR) before and after treatment were analyzed. Binary logistic regression analysis is used to establish a mathematical model of the relationship between these indexes and the outcome of severe COVID-19 patients. The receiver operating characteristic(ROC) curve is used to further explore the prognosis value of MPV, P-LCR, NLR separately and jointly in COVID-19 patients. Compare to the control group, WBC and NE# increase ( Z=-5.63, P<0.01; Z=-9.19, P<0.01) and LY# decrease ( Z=-9.34, P<0.01) in the severe group; NLR increase with the aggravation of the disease, there is significant difference between groups ( Z=17.61, P<0.01); PLT, PDW, MPV and P-LCR decrease with the aggravation of the disease, there is significant difference between groups ( Z=9.47, P<0.01; Z=11.41, P<0.01; Z =16.76, P<0.01; Z=13.97, P<0.01). Binary logistic regression analysis shows MPV, P-LCR and NLR have predictive value for severe COVID-19 patients. There is a negative correlation between MPV, P-LCR and severe COVID-19 patients ( OR=1.004, P=0.034; OR=1.097, P=0.046). There is a positive correlation between NLR and severe COVID-19 patients ( OR=1.052, P=0.016). MPV and P-LCR of patients with good prognosis after treatment were significantly higher than those before treatment ( Z=-6.47, P<0.01; Z=-5.36, P<0.01). NLR was significantly lower than that before treatment ( Z=-8.13, P<0.01). MPV and P-LCR in poor prognosis group were significantly lower than those before treatment ( Z=-9.46, P<0.01; Z=-6.81, P<0.01). NLR was significantly higher than that before treatment ( Z=-3.24, P<0.01). There were significant differences between good and poor prognosis groups before and after treatment in MPV, P-LCR and NLR ( P<0.01). Combination of these three indexes, ROC shows the AUC is 0.931, the sensitivity is 91.5%, the specificity is 94.1%, the positive predictive value is 88.9%, and the negative predictive value is 87.4%, which is better than any of these indexes separately. Changes in these parameters are closely related to clinical stage of COVID-19 patients. MPV, P-LCR and NLR are of great value in the prediction and prognosis of severe COVID-19 patients.

Objective:To investigate the effects of acupuncture combined with hyperbaric oxygen on neurological function and cerebral blood flow of pediatric patients with severe viral encephalitis.Methods:A total of 100 pediatric patients with severe viral encephalitis admitted to the Department of Pediatrics of the Second Affiliated Hospital of Zhengzhou University from August 2016 to December 2018 were selected as research objects and randomly divided into the observation group ( n=50) and the control group ( n=50) by the random number table method. Patients in both groups received conventional medical treatment. The patients in the control group were supplemented with hyperbaric oxygen, while the patients in the observation group were treated with acupuncture on the basis of the treatment in the control group. The clinical symptoms, the recovery time of body signs, the score of National Institute of Health stroke scale (NIHSS), the score of Glasgow coma scale (GCS), and the cerebral blood flow indexes were compared between the two groups. Results:The defervescence period, the time required for headache and vomiting to subside, the recovery time of consciousness, and the improvement time of electroencephalogram in the observation group were all shorter than those in the control group, the differences were statistically significant ( P<0.05). After treatment, the NIHSS score of the observation group was lower than that of the control group, but the GCS score of the observation group was higher than that of the control group ( P<0.05). After treatment, the systolic blood flow velocity (Vs), mean flow velocity (Vm), and pulsatility index (PI) in the two groups were lower than those before treatment, and the above-mentioned indexes of the observation group were lower than those of the control group, the differences were statistically significant ( P<0.05). Conclusion:In the treatment of severe viral encephalitis in children, acupuncture combined with hyperbaric oxygen can improve the clinical symptoms and signs, alleviate the severity of neurologic impairment, promote the recovery of consciousness, decrease the cerebral blood flow indexes, and speed up rehabilitation.

Objective:To investigate the effects of acupuncture combined with hyperbaric oxygen on neurological function and cerebral blood flow of pediatric patients with severe viral encephalitis.Methods:A total of 100 pediatric patients with severe viral encephalitis admitted to the Department of Pediatrics of the Second Affiliated Hospital of Zhengzhou University from August 2016 to December 2018 were selected as research objects and randomly divided into the observation group ( n=50) and the control group ( n=50) by the random number table method. Patients in both groups received conventional medical treatment. The patients in the control group were supplemented with hyperbaric oxygen, while the patients in the observation group were treated with acupuncture on the basis of the treatment in the control group. The clinical symptoms, the recovery time of body signs, the score of National Institute of Health stroke scale (NIHSS), the score of Glasgow coma scale (GCS), and the cerebral blood flow indexes were compared between the two groups. Results:The defervescence period, the time required for headache and vomiting to subside, the recovery time of consciousness, and the improvement time of electroencephalogram in the observation group were all shorter than those in the control group, the differences were statistically significant ( P<0.05). After treatment, the NIHSS score of the observation group was lower than that of the control group, but the GCS score of the observation group was higher than that of the control group ( P<0.05). After treatment, the systolic blood flow velocity (Vs), mean flow velocity (Vm), and pulsatility index (PI) in the two groups were lower than those before treatment, and the above-mentioned indexes of the observation group were lower than those of the control group, the differences were statistically significant ( P<0.05). Conclusion:In the treatment of severe viral encephalitis in children, acupuncture combined with hyperbaric oxygen can improve the clinical symptoms and signs, alleviate the severity of neurologic impairment, promote the recovery of consciousness, decrease the cerebral blood flow indexes, and speed up rehabilitation.

This study was aimed to investigate the effect of Forkhead Box G1 (FOXG1) on the epithelial-mesenchymal transition (EMT) of colorectal cancer (CRC) cells and the underlying mechanism. For this purpose, FOXG1 lentiviral interference (shRNA) plasmid and expression plasmid were constructed. Western blotting was used to analyze the expression of FOXG1 protein in five CRC cells, namely RKO, SW480, SW620, LoVo and DLD-1. The shRNA fragment of FOXG1 (shFOXG1) was designed and synthesized. Recombinant plasmids were obtained with the aid of DNA recombination technique. Double digestion and sequencing were used to identify the recombinant plasmids, and then lentivirus packaging, purification and stable transfection were carried out. Additionally, stable CRC cell lines were screened out. The changes of FOXG1 knockdown and overexpression efficiency, E-cadherin, Vimentin, Fibronectin, Snail, Twist mRNA and protein were investigated respectively by Western blotting and qRT-PCR analysis. Furthermore, the changes of cell morphology after knockdown and cell migration ability were evaluated respectively with optical microscopy, scratch test and Transwell assay. FOXG1 had the highest protein expression in RKO and the lowest in DLD-1 among the five CRC cells. Compared with those of the control group, the cell morphology in FOXG1 knockdown RKO group was changed from spindle into round or polygonal shape, cell polarization was enhanced and tight junction assembly was acclerated while cell migration distance was noticeably decreased. Moreover, the number of cells invaded and migrated through chambers was significantly reduced. Among these key factors of EMT, the expression of E-cadherin was increased while the expressions of Vimentin, Fibronectin, Snail and Twist were decreased. The opposite was the case in the overexpressed FOXG1 group. The overexpression of FOXG1 in CRC promoted the invasion and metastasis of CRC cells and played a crucial role in regulating the EMT. Thus, FOXG1 might be a novel therapeutic target in CRC treatment.

Objective To identity the characteristic metabolites of platelets activation by Plasma metabolic Profiling in acute myocardium infarction ( AMI ) patients.Methods From August 2012 to February 2013, samples in three groups were collected at Tianjin Third Central hospital, including AMI group (25 clinically diagnosis myocardial infarction, 14 male, 11 female, average age 67 ±13 ) , control group(A) and simulation platelet activation group(B) (A and B group composed of 29 health volunteers, 11 male 18 female, average age 65 ±12 ) .After collagen platelet activation on B group, HPLC-LTQ Orbitrap XL MS platform was used to analyze the serum metabolic profiling in three groups respectively.Principal component analysis ( PCA) model and partial least squares-discriiminate analysis ( OPLS-DA) model were established to select characteristic metabolites in A and B group, and then tested in X group to find common ions.Results 20 characteristic metabolites were selected in A and B group.3 different lysophosphatidyl choline, sphingosine 1-phosphate, ethanol amine amides, sphingosine choline phosphate, thromboxane, 14-methyl hexadecanoic acid showed the same changing trend and were significant different between B group and AMI group.Conclusions Characteristic ions selected by metabolic profiling technology had significant distinguishing ability for AMI patients and health control.They may provide early diagnosis for AMI.

Objective To observe influence of atorvastatin combining with berberine on blood cholesterol level and carotid atherosclerotic plaques in patients with acute artery atherosclerosis cerebral infarction disease. Methods Fif-ty-five cases of acute cerebral infarction patients were randomized into 3 groups: group A (n=28), group B (n=11) and group C (n=16). Group A, B or C received atorvastatin 20 mg (qn), atorvastatin 40 mg (qn) or atorvastatin 20 mg (qn) +berberine 0.4 g (tid), respectively. All groups were then followed up for 3 months. The total cholesterol(TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C),high-density lipoprotein-cholesterol(HDL-C and the changes of carotid atherosclerotic plaques including total plaque area (TPA), crouse score,carotid intima-media thickness (IMT) and the stability of carotid plaques as well as the serum levels of creatinine(Scr), alanine aminotransferase(ALT), aspartate aminotransferase(AST), were compared among three groups. Results After 3 months, the TC, TG and LDL-C were de-creased in all three groups. There were statistically significant differences in the TC and LDL-C among these three groups (P=0.011,P=0.033) after treatment. The compliance rate of group C (75.0%) was significantly higher than group A ( 32.1% ) and group B (45.5%) in LDL-C (P=0.026). Both berberine combining with atorvastatin and atorvastatin monotherapy(20mg could significantly reduce crouse score. Conclusions Berberine can significantly enhance the benefi-cial effects of atorvastatin on LDL-C and the crouse score in patients with acute artery atherosclerosis cerebral infarction patients.