Objective:To explore the risk factors of septic acute kidney injury (sAKI) in patients with sepsis, construct a predictive model for sAKI, verify the predictive value of the model, and develop a dynamic nomogram to help clinical doctors identify patients with high-risk sAKI earlier and more easily.Methods:A cross-sectional study was conducted. A total of 245 patients with sepsis admitted to intensive care unit (ICU) of the Affiliated Hospital of Jining Medical University from May 2013 to November 2023 were enrolled as the research subjects. The patients were divided into sAKI group and non-sAKI group based on whether they suffered from sAKI during ICU hospitalization. The differences of the demographic, clinical and laboratory indicators of patients between the two groups were compared. Logistic ordinal regression analysis was performed to analyze the imbalanced variables between the two groups, and to construct a sAKI predictive model. The predictive value of the sAKI predictive model was evaluated through 5-fold cross validation, calibration curve, and decision curve analysis (DCA), and to develop an online dynamic nomogram for the predictive model.Results:A total of 245 patients were enrolled in the final analysis. 110 (44.9%) patients developed sAKI during ICU hospitalization and 135 (55.1%) patients did not develop sAKI. Compared with the non-sAKI group, the patients in the sAKI group had higher ratios of female, hypertension, invasive mechanical ventilation (IMV), renal replacement therapy (RRT), vasopressin usage, and neutrophil count (NEU), aspartate aminotransferase (AST), blood urea nitrogen (BUN), serum creatinine (SCr), uric acid (UA), Na +, K +, procalcitonin (PCT), acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, and sequential organ failure assessment (SOFA) score. Multivariate Logistic ordinal regression analysis showed that female [odd ratio ( OR) = 2.208, 95% confidence interval (95% CI) was 1.073-4.323, P = 0.020], hypertension ( OR = 2.422, 95% CI was 1.255-5.073, P = 0.012), vasopressin usage ( OR = 2.888, 95% CI was 1.380-6.679, P = 0.002), and SCr ( OR = 1.015, 95% CI was 1.009-1.024, P < 0.001) were independent risk factors for sAKI in septic patients, and a sAKI predictive model was constructed: ln[ P/(1+ P)] = -4.665+0.792×female+0.885×hypertension+1.060×vasopressin usage+0.015×SCr. The 5-fold cross validation showed that the average area under the receiver operator characteristic curve (AUC) was 0.860, indicating the sAKI predictive model had a good performance. The calibration curve analysis showed that the calibration degree of the sAKI predictive model was good. DCA showed that the net profit of the sAKI predictive model was relatively high. A static nomogram and an online dynamic nomogram were constructed for the sAKI predictive model. Compared with the static nomogram, the dynamic nomogram allowed for manual selection of corresponding patient characteristics and viewing the corresponding sAKI risk directly. Conclusions:Female, hypertension, vasopressin usage, and SCr are the main risk factors for sAKI in patients with sepsis. The sAKI predictive model constructed based on these factors can help clinical doctors identifying high-risk patients as early as possible, and intervene in a timely manner to provide preventive effects. Compared with the common static nomogram, online dynamic nomogram can make predictive models clearer, more intuitive, and easier.

This article reported a case of pyruvate dehydrogenase E1-α deficiency suggested by abnormal brain development during prenatal ultrasound imaging. Prenatal ultrasound revealed a mild enlargement of bilateral cerebral ventricles and the possibility of intracranial hemorrhage in the fetus at 25 +1 weeks of gestation. MRI showed the fetus with absent corpus callosum, enlarged bilateral cerebral ventricles and paraventricular cysts. After genetic counseling and careful consideration, the couple opted for pregnancy termination. To clarify the cause of the disease, whole-exome sequencing was performed on the fetal skin to detect possible variants, and which revealed a frameshift mutation c.924_930dup(p.R311Gfs*5) in exon 10 of the PDHA1 gene. Sanger sequencing confirmed the mutation was a de novo pathogenic variant, indicating that the fetus was affected by pyruvate dehydrogenase E1-α deficiency.

Objective:To explore the value of different radiomics models based on machine learning in predicting the risk of distant recurrence and metastasis of triple-negative breast cancer after neoadjuvant therapy.Methods:The clinical and imaging data of 150 patients with triple-negative breast cancer (TNBC) confirmed by histopathology were retrospectively analyzed. All patients underwent neoadjuvant chemotherapy and surgical resection from August 2011 to May 2017 in Fudan University Shanghai Cancer Center and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. One hundred and nine patients from Shanghai Fudan University Shanghai Cancer Center were used as the training group, and 41 patients from Ruijin Hospital, Shanghai Jiao Tong University School of Medicine were used as the validation group. The features were extracted from dynamic contrast-enhanced MRI (DCE-MRI) before treatment and were added with time domain features innovatively. Least absolute shrinkage and selection operator cross validation and recursive feature elimination were applied to select features. Six different supervised machine learning algorithms (logistic regression, linear discriminant analysis, k-nearest neighbor, naive bayesian, decision tree, support vector machine) were used to predict the prognosis. ROC curve, accuracy and F1 measure were used to evaluate the performance of the six algorithms, and also verified by the validation group.Results:The support vector machine algorithm had the best predictive effect in the recurrence and metastasis model based on 15 features, with the highest area under curve (training group was 0.917, validation group was 0.859), and the highest accuracy rate (training group was 87.5%, validation group was 82.9%) and the highest F1 measure (training group was 0.800, validation group was 0.741). In addition, of the 15 imaging features, 12 were the time domain features and 3 were spatial features.Conclusion:With the help of the time domain features and machine learning algorithms, radiomics signatures based on preoperative DCE-MRI can help predict the distant prognosis for TNBC after neoadjuvant chemotherapy and provide support for clinical decision making and follow-up management.

Objective: To investigate the effects of sIL-13Rα2 on the apoptosis of goblet cell in nasal mucosa of allergic rhinitis rats. Methods: Forty healthy male Wistar rats were randomly divided into 4 groups (10 rats per group): control group (group A), AR group (group B), sIL-13Rα2 group (group C) and triamcinolone acetonide group (group D). Ovalbumin (OVA) and aluminum hydroxide were used to establish the AR rat model. After the establishment of AR rat models, 50 μl PBS, 100 μg/50 μl IL-13Rα2 and 3.5 μg/50 μl triamcinolone acetonide were respectively dropped into each nasal cavity of every rat two times a week from 4 to 10 week in group B, group C and group D. Group A was operated with saline instead of OVA. The nasal mucosa tissues were collected at 24 h after the final administration. AB-PAS staining method was used to detect the quantity and secretion of goblet cells in the nasal mucosa tissue of all groups. Immunohistochemistry method was used to detect the expression of Bax proteins.Apoptosis was detected by TUNEL method.ANOVA analysis was used to compare multiple groups, and LSD-t test was used to compare the two groups.Pearson correlation analysis was used to analyze the correlation between the Bax positive cell rate of goblet cells and the rate of apoptotic cells. The difference was statistically significant with P<0.05. Results: Compared with group A, there were more goblet cells and hypersecretion of mucus in the nasal mucosa tissue of rats in group B while fewer in group C. The goblet cells in group C and group D were significantly fewer than that in group B (0.639 00±0.831 vs 0.956 7±0.980, 0.661 90±0.657 vs 0.956 7±0.980, t value was 2.748, 2.767, respectively, all P<0.05). The immunohistochemistry results showed that the positive expression rates of Bax protein in goblet cells of group C and group D were significantly higher than that in group B (0.880 2±0.125 vs 0.568 7±0.953, 0.938 4±0.200 vs 0.568 7±0.953, t value was -2.292, -2.685, respectively, all P<0.05). The apoptosis rates of goblet cell in nasal mucosa of group C and group D were also significantly higher than that in group B (0.516 0±0.079 vs 0.274 0±0.056, 0.535 4±0.829 vs 0.274 0±0.056, t value was -17.671, -2.225, respectively, all P<0.05). The expression of Bax protein and apoptosis of goblet cells were positively correlated (r=0.859, P<0.01). Conclusion sIL-13Rα2 can induce apoptosis of the goblet cells in nasal mucosa of allergic rhinitis rats, by inhibiting IL-13 and up regulating Bax.

Objective To explore the clinical efficacy and safety of panaxadiol saponins for the treatment of non-small cell lung cancer(NSCLC) with chemotherapy-induced leukopenia.Methods 92 NSCLC patients with leukopenia after chemotherapy were selected and divided into the observation group (46 cases) and the control group (46 cases) by random number table method.On the second day after the chemotherapy,the observation group was given panaxadiol saponins capsules,3 tablets/time,2 times/day.The control group was orally given placebo or reserpine,4 weeks for one course of treatment,the two groups were continuously treated for two courses.The clinical efficacy,number of leukocytes,improvement of TCM symptoms and adverse reactions were evaluated.Results After treatment for 4 weeks and 8 weeks,the WBC counts of the observation group were (4.48 ±0.77) × 109/L and (4.92 ± 0.89) × 109/L,respectively,which were significantly higher than those of the control group[(4.02 ± O.93) × 109/L and (4.57 ± 0.86) × 109/L],the differences were statistically significant(t =8.24,8.41,all P ＜ 0.05).After treatment for 4 weeks and 8 weeks,the TCM syndrome scores of the observation group were (24.02 ± 5.91)points and (21.73 ± 4.14) points,respectively,which were lower than those of the control group [(26.33 ± 5.08) points and (23.14 ± 3.90) points],the differences were statistically significant (t =9.68,9.63,all P ＜ 0.05).After treatment for 4 weeks and 8 weeks,the total effective rates of TCM were 76.09％ (35/46) and 82.61％ (38/46),respectively,which were significantly higher than those of the control group [63.04％ (29/46) and 63.04％ (29/46)],the differences were statistically significant(x2 =10.32,8.61,all P ＜ 0.05).The effective rates of leukopenia improvement of the observation group after treatment for 4 weeks and 8 weeks were 69.57％ (32/46) and 78.26％ (36/46),respectively,which were higher than those of the control group [56.52％ (26/46) and 65.22％ (30/46)],the differences were statistically significant(t =9.38,9.51,all P ＜ 0.05).There were no significant differences in adverse reactions between the two groups (P ＞ 0.05).Conclusion Panaxadiol saponins in the treatment of NSCLC chemotherapy-induced leukopenia can significantly improve the number of white blood cells,improve the clinical symptoms,and it has good safety.

OBJECTIVE: To study the role of JNK (c-Jun N-terminal kinase) signal transduction pathway on the nasal mucosa remodeling in allergic rhinitis rats, to explore whether IL-1β participates the nasal mucosa remodeling in allergic rhinitis by JNK signal transduction pathway. METHOD: Totally 60 male Wistar rats (weighing about 200-250 g)were randomly divided into A (AR group) and B group (control group). The rats in A group were sensitized for inducing AR by intraperitoneal injection ovalbumin and Al(OH)₃. Ovalbumin was respectively dropped in each nasal cavity of every rat for 4,8,12 weeks(A4,A8,or A12 group) each had 10 rats. The rats in B group were sensitized by intraperitoneal injection saline. Saline was respectively dropped in each nasal cavity of every rat for 4,8, 12 weeks(B4, B8, or B12 group), and each had 10 rats. The concentration of IL-1β in serum and nasal lavage fluid were tested by ELASA. The protein expressions of P-JNK and P-c-Jun were detected by immunohistochemical technique. Linear correlation analysis showed the correlation between levels of IL-1β in serum and P-JNK protein, levels of IL-1β in nasal lavage fluid and P-JNK protein. RESULT: The concentrations of IL-1β in serum and nasal lavage fluid of A group were all significantly higher than those of the corresponding B group (all P < 0.01). Compared with A4 group and A8 group, concentrations of IL-1β in nasal lavage fluid of A12 group were significantly increased (all P < 0.01). However the levels of IL-1β in serum were not significantly different among them (all P > 0.05). Mean absorbance values of P-JNK and P-c-Jun in A group were significantly higher than those in corresponding B group (all P < 0.01) and compared with A4 group and A8 group, those of A12 group were significantly increased (all P < 0.01). Strong positive correlation were found between P-JNK and concentration of IL-1β in serum or nasal lavage fluid (r = 0.835 and r = 0.902, all P < 0.01). CONCLUSION JNK signal transduction pathway plays important role in the nasal mucosa remodeling in allergic rhinitis rats. IL-1β participates in AR nasal mucosa remodeling possibly partly through activating JNK signal transduction pathway.
Animals ; Disease Models, Animal ; Interleukin-1beta ; metabolism ; JNK Mitogen-Activated Protein Kinases ; metabolism ; MAP Kinase Signaling System ; Male ; Nasal Mucosa ; pathology ; Ovalbumin ; Paranasal Sinuses ; Rats ; Rats, Wistar ; Rhinitis, Allergic ; metabolism ; pathology ; Signal Transduction

OBJECTIVEThis study aims to evaluate the efficacy and safety of crizotinib for advanced ALK-positive non-small cell lung cancer (NSCLC) patients.

METHODSTwenty-eight patients with advanced ALK-positive NSCLC were given orally crizotinib 250 mg b. i.d., and were followed up to evaluate the therapeutic efficacy and safety.

RESULTSAmong the 28 patients, the objective response rate (ORR) was 71.4% (20/28) and disease control rate (DCR) was 92.9% (26/28). Three patients achieved complete response. Seventeen patients had partial response. The most common drug-related adverse events were mild flickering vision and gastrointestinal reaction. Eleven patients experienced flickering vision. Nine patients had nausea and vomiting. Eight patients had diarrhea. They were all reversible and of grade I or II. Only one patient had grade III myelosuppression. Among the 28 patients, 16 cases were disease-free and 12 cases had progressive disease, with a progression-free survival of 8.2 months.

CONCLUSIONSCrizotinib is effective and tolerable in the treatment of advanced ALK-positive NSLCC. However, its long-term treatment efficacy requires to be further studied.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; enzymology ; pathology ; Diarrhea ; chemically induced ; Disease-Free Survival ; Humans ; Lung Neoplasms ; drug therapy ; enzymology ; pathology ; Nausea ; chemically induced ; Protein Kinase Inhibitors ; adverse effects ; therapeutic use ; Pyrazoles ; adverse effects ; therapeutic use ; Pyridines ; adverse effects ; therapeutic use ; Receptor Protein-Tyrosine Kinases ; Vomiting ; chemically induced

Objective This study aims to evaluate the efficacy and safety of crizotinib for advanced ALK?positive non?small cell lung cancer ( NSCLC) patients. Methods Twenty?eight patients with advanced ALK?positive NSCLC were given orally crizotinib 250 mg b. i. d., and were followed up to evaluate the therapeutic efficacy and safety. Results Among the 28 patients, the objective response rate ( ORR) was 71.4%(20/28) and disease control rate (DCR) was 92.9% (26/28). Three patients achieved complete response. Seventeen patients had partial response. The most common drug?related adverse events were mild flickering vision and gastrointestinal reaction. Eleven patients experienced flickering vision. Nine patients had nausea and vomiting. Eight patients had diarrhea. They were all reversible and of grade Ⅰ or Ⅱ. Only one patient had grade Ⅲ myelosuppression. Among the 28 patients, 16 cases were disease?free and 12 cases had progressive disease, with a progression?free survival of 8.2 months. Conclusions Crizotinib is effective and tolerable in the treatment of advanced ALK?positive NSLCC. However, its long?term treatment efficacy requires to be further studied.

Objective This study aims to evaluate the efficacy and safety of crizotinib for advanced ALK?positive non?small cell lung cancer ( NSCLC) patients. Methods Twenty?eight patients with advanced ALK?positive NSCLC were given orally crizotinib 250 mg b. i. d., and were followed up to evaluate the therapeutic efficacy and safety. Results Among the 28 patients, the objective response rate ( ORR) was 71.4%(20/28) and disease control rate (DCR) was 92.9% (26/28). Three patients achieved complete response. Seventeen patients had partial response. The most common drug?related adverse events were mild flickering vision and gastrointestinal reaction. Eleven patients experienced flickering vision. Nine patients had nausea and vomiting. Eight patients had diarrhea. They were all reversible and of grade Ⅰ or Ⅱ. Only one patient had grade Ⅲ myelosuppression. Among the 28 patients, 16 cases were disease?free and 12 cases had progressive disease, with a progression?free survival of 8.2 months. Conclusions Crizotinib is effective and tolerable in the treatment of advanced ALK?positive NSLCC. However, its long?term treatment efficacy requires to be further studied.

Objective To investigate whether fasting obestatin level is different in patients with impaired glucose tolerance or type 2 diabetes, and to explore the association between obestatin and lipid metabolism. Methods Eighty-four subjects without known diabetes were divided into three groups: normal glucose tolerance(NGT), impaired glucose tolerance (IGT) and type 2 diabetes (DM) Plasma obestatin levels were measured with a radioimmunoassay. The relationship between fasting obestatin levels and metabolic parameters was also analyzed. Results Fasting obestatin levels were lower in DM group [(2.82±0.78)ng/ml] and IGT group [(3.25±0.29)ng/ml] than in NGT group[(3.55±0.57) ng/ml, P＜0.01]. Triglycerides and low density lipoprotein cholesterol levels gradually increased among the three groups (P＜0.05). Multiple linear regression analysis revealed fasting obestatin level was independently associated with waist-to-hip ratio, triglyeride and low density lipoprotein cholesterol. The regression equation was obestatin=6.953-3.412×W/H-0.175×TG-0.123×LDL-C. Conclusions The decreased obestatin may be associated with IGR and T2DM, and obestatin level may be associated with lipid metabolism.