Clinical and biochemical characteristics, and outcome in 33 patients with ceftriaxone-induced liver injury.

PURPOSE: To summarize the clinical and biochemical characteristics of patients with ceftriaxone-induced liver injury and guide the selection of safe medication. METHODS: Retrieved domestic and foreign databases from inception to October 2023, collected case data conforming to ceftriaxone-induced liver injury, and statistically analyzed the data. RESULTS: A total of 617 articles were retrieved, and 16 articles with 33 cases (10 children, 23 adults) were included. Males represented 60% (18/30), with a male-to-female ratio of 1.5:1. The age of onset ranged from 2 days to 96 years, with 15 of 23 adults (65%) over 55 years old. The time from ceftriaxone use to liver injury fluctuated between 0.5 and 47 days. Only 9 patients (27.3%, 9/33) had clinical symptoms, and the clinical classification was dominated by cholestatic injury (46.2%, 12/26). There was a significant difference in the clinical classification of ceftriaxone-induced liver injury between children and adults (P = 0.0126), with hepatocellular injury predominating in children and cholestatic injury predominating in adults. The severity of liver injury was mainly mild (66.7%, 12/18). Peak values of alanine aminotransferase ranging from 228.5 to 8098 U/L, aspartate aminotransferase ranging from 86.7 to 21575 U/L, alkaline phosphatase ranging from 143 to 2434 U/L, and total bilirubin ranging from 3.35 to 66.1 mg/dL. There was a significant difference in peak values of alkaline phosphatase between children and adults (P = 0.027), with a higher peak value of alkaline phosphatase in adults (1039 ± 716.4 U/L vs. 257 ± 134.9 U/L). Patients with normal imaging examinations accounted for the majority (61.5%, 7/13). The prognosis of 32 patients (97%, 32/33) was good, and one child with sickle cell anemia who developed immune hemolysis, progressive renal failure, and acute liver injury after using ceftriaxone died in the end. CONCLUSION: Ceftriaxone-induced liver injury can occur at any age, with a higher risk in the elderly, and age may be related to the clinical classification. Although the clinical manifestations are not specific, close monitoring of liver biochemical indicators during the use can detect liver injury early. Most cases have a good prognosis, but for people with concomitant sickle cell anemia, it is necessary to be vigilant about the occurrence of severe hemolytic anemia.

Screening for Wilson's disease in acute liver failure: A new scoring system in children.

Background: Wilson's disease (WD) is a rare cause of acute liver failure (ALF) and has a high fatality rate. Rapid and accurate diagnosis is important for ALF because of WD (ALF-WD). Our objective was to establish a simple, rapid, and accurate diagnostic test to distinguish ALF-WD from non-WD ALF (NWDALF) in children. Materials and methods: The data from all cases with pediatric ALF were retrospectively collected and analyzed. We performed receiver operator characteristics curve (ROC) analysis and confirmed the optimum cut-off points. Results: Fifty-eight patients with pediatric ALF (12 with WD, 46 with other etiologies) were included. Older age was observed in ALF-WD compared to NWDALF (11.16 ± 2.51 years vs. 3.34 ± 3.81 years, p < 0.001). An analysis based on routine biochemical testings revealed that total bilirubin (TBil), direct bilirubin, indirect bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST:ALT ratio, alkaline phosphatase (ALP), ALP:TBil ratio, serum albumin, gamma-glutamyl transferase, cholinesterase, hemoglobin, and platelet were statistically significant between the ALF-WD and NWDALF groups. The optimum cut-off points were obtained through ROC analysis. A scoring system was formed by assigning a score of 1 or 0 to patients who met the 13 cut-off points. Using ROC analysis, we determined a cut-off point of ≥ 6.5 for ALF-WD with 91.7% sensitivity and 97.8% specificity (p < 0.0001). In addition, a best cut-off point of ≥ 1.5 based on only five variables (ALT, AST, AST:ALT ratio, ALP, and ALP:TBil ratio), had 100% sensitivity and 91.3% specificity for ALF-WD (p < 0.0001). Based on this, when age was calculated as the sixth indicator, the best cut-off value of ≥ 2.5 had 100% sensitivity and 97.8% specificity (p < 00.0001). Conclusion: Our study developed a new scoring system that consists of simple laboratory tests with good sensitivity and specificity and can be used by clinicians to quickly distinguish ALF-WD from NWDALF in children.

Differentially expressed gene profile and relevant pathways of the traditional Chinese medicine cinobufotalin on MCF­7 breast cancer cells.

Cinobufotalin is a chemical compound extracted from the skin of dried bufo toads that may have curative potential for certain malignancies through different mechanisms; however, these mechanisms remain unexplored in breast cancer. The aim of the present study was to investigate the antitumor mechanism of cinobufotalin in breast cancer by using microarray data and in silico analysis. The microarray data set GSE85871, in which cinobufotalin exerted influences on the MCF­7 breast cancer cells, was acquired from the Gene Expression Omnibus database, and the differentially expressed genes (DEGs) were analyzed. Subsequently, protein interaction analysis was conducted, which clarified the clinical significance of core genes, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to analyze cinobufotalin­related pathways. The Connectivity Map (CMAP) database was used to select existing compounds that exhibited curative properties similar to those of cinobufotalin. A total of 1,237 DEGs were identified from breast cancer cells that were treated with cinobufotalin. Two core genes, SRC proto­oncogene non­receptor tyrosine kinase and cyclin­dependent kinase inhibitor 2A, were identified as serving a vital role in the onset and development of breast cancer, and their expression levels were markedly reduced following cinobufotalin treatment as detected by the microarray of GSE85871. It also was revealed that the 'neuroactive ligand­receptor interaction' and 'calcium signaling' pathways may be crucial for cinobufotalin to perform its functions in breast cancer. Conducting a matching search in CMAP, miconazole and cinobufotalin were indicated to possessed similar molecular mechanisms. In conclusion, cinobufotalin may serve as an effective compound for the treatment of a subtype of breast cancer that is triple positive for the presence of estrogen, progesterone and human epidermal growth factor receptor­2 receptors, and its mechanism may be related to different pathways. In addition, cinobufotalin is likely to exert its antitumor influences in a similar way as miconazole in MCF­7 cells.

Upregulated miR­203a­3p and its potential molecular mechanism in breast cancer: A study based on bioinformatics analyses and a comprehensive meta­analysis.

Breast cancer (BC) has been identified as the leading malignancy in women worldwide. However, the potential molecular mechanism of microRNA (miR)­203a­3p in BC remains to be elucidated. The present study evaluated the expression of miR­203a­3p in BC and adjacent normal tissue in several publically available datasets. The distinguishability of precursor miR­203a and miR­203a­3p in BC tissue and adjacent breast tissue was assessed using receiver operating characteristic (ROC) and summarized ROC (sROC) approaches. In addition, gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes pathway analysis and protein­protein interaction analysis were performed to determine the potential molecular mechanism of miR­203a­3p in BC. It was identified that the expression of precursor miR­203a was markedly upregulated in 1,077 BC tissue samples compared to 104 adjacent breast tissue samples from The Cancer Genome Atlas. Additionally, an increasing trend in miR­203a­3p expression was observed in 756 BC tissue samples compared with 76 adjacent breast tissue samples from the University of California Santa Cruz Xena project. In addition, a comprehensive meta­analysis suggested that the expression of miR­203a­3p was markedly increased in 2,444 BC tissue samples compared with 559 adjacent breast tissue samples. The area under the curve of the ROC and sROC revealed that miR­203a­3p expression was able to distinguish between BC tissue and adjacent breast tissue. However, miR­203a­3p exhibited no prognostic value in BC. The results of GO enrichment demonstrated that the miR­203a target genes were associated with 'plasma membrane integrity', 'cell surface receptor linked signal and transduction' and '3',5'­cyclic nucleotide phosphodiesterase activity'. 'Purine metabolism' was identified as the pathway with the most enrichment of miR­203a­3p target genes in BC. The present study also identified insulin­like growth factor receptor (IGF1) as a hub gene associated with miR­203a in BC. In summary, miR­203a­3p may enhance the development and oncogenesis of BC, and IGF1 was defined as a hub gene of miR­203a­3p in BC.

In vitro-activated tumor-bearing host T cells and the effectiveness of tumor vaccine immunotherapy.

BACKGROUND AND OBJECTIVE: Vaccination during periods of lymphopenia may facilitate immune responses to weak self-antigens and enhance antitumor immunity. The objective of this study was to determine the effectiveness of tumor vaccine immunotherapy combined with immune reconstruction using tumor-bearing host immune cells in lymphopenia, and to investigate the role of tumor-bearing host T cells activated in vitro during immunotherapy. DESIGN AND SETTING: Animal study conducted in the First Affiliated Hospital of Xi'an Jiaotong University from January 2009 to January 2010. PATIENTS AND METHODS: Lymphopenia was induced by cyclophosphamide. A reconstituted immune system with different syngeneic lymphocytes was employed, including lymphocytes from naïve rats (unsensitized group), tumor-bearing rats (tumor-bearing group), and tumor-bearing rats activated in vitro (activated group). All rats were immunized with granulocyte-macrophage colony-stimulating factor (GM-CSF)-modified NuTu-19 ovarian cancer (GM-CSF/NuTu-19) cells. Tumor vaccine-draining lymph nodes (TVDLNs) were harvested, and then stimulated to induce effector T cells (T(E)). T(E) were then adoptively transferred to rats bearing a 3-day pre-established abdominal tumor (NuTu-19), and the survival rate was calculated. RESULTS: Compared with the unsensitized group, the levels of interleukin-2 (IL-2) were significantly lower in the tumor-bearing group, whereas that of IL-4 were significantly higher (P<.05). The number of CD4+ T cells secreting interferon-γ and the specific cytotoxicity of CD8+ cytotoxic T lymphocytes were significantly lower (P<.05). The survival was significantly higher in the activated group compared with the other groups. CONCLUSIONS: Lymphocytes from tumor-bearing rats activated in vitro can effectively reverse the immunosuppressive effects of tumor-bearing hosts.

Influences of sodium carbonate on physicochemical properties of lansoprazole in designed multiple coating pellets.

Lansoprazole (LSP), a proton-pump inhibitor, belongs to class II drug. It is especially instable to heat, light, and acidic media, indicating that fabrication of a formulation stabilizing the drug is difficult. The addition of alkaline stabilizer is the most powerful method to protect the drug in solid formulations under detrimental environment. The purpose of the study was to characterize the designed multiple coating pellets of LSP containing an alkaline stabilizer (sodium carbonate) and assess the effect of the stabilizer on the physicochemical properties of the drug. The coated pellets were prepared by layer-layer film coating with a fluid-bed coater. In vitro release and acid-resistance studies were carried out in simulated gastric fluid and simulated intestinal fluid, respectively. Furthermore, the moisture-uptake test was performed to evaluate the influence of sodium carbonate on the drug stability. The results indicate that the drug exists in the amorphous state or small (nanometer size) particles without crystallization even after storage at 40°C/75% for 5 months. The addition of sodium carbonate to the pellet protects the drug from degradation in simulated gastric fluid in a dose-dependent manner. The moisture absorbed into the pellets has a detrimental effect on the drug stability. The extent of drug degradation is directly correlated with the content of moisture absorption. In conclusion, these results suggest that the presence of sodium carbonate influence the physicochemical properties of LSP, and the designed multiple coating pellets enhance the drug stability.

[Evaluation of immune reconstitution with in vitro-activated T cells from a tumor-bearing host].

AIM: To evaluate the reconstituted immune system with in vitro-activated T cells from tumor-bearing rats coupled with ovarian cancer vaccination. METHODS: Fischer 344 female rats were injected with cyclophosphamide (CY) as a lymphopenia (LP) model. The immune systems of the rats were reconstituted with in vitro-activated T cells from the same individuals. GM-CSF-modified ovarian cancer cells lines (NuTu-19) were injected within 24 h after immune reconstitution. The tumor vaccine draining lymph nodes (TVDLN) were harvested 8-10 days after vaccination and analyzed by FACS. The proliferative capacity of dendritic cells (DCs) was measured by the levels of MHC-II and CD86 molecules. The activation of T cells was monitored by the percentage of FITC-CD4 and PE-CD8 cells. The biological function of DCs such as processing and presenting antigens was assayed by immature DCs' phagocytosis of FITC-Dextran. RESULTS: Immune reconstitution with in vitro-activated T cells produced significantly more DCs, T cells and functionally enhanced immature DCs out of TVDLN. CONCLUSION: Reconstituting immune system with in vitro-activated T cells from a tumor-bearing host coupled with ovarian cancer vaccination during lymphocytopenia may selectively expand and activate particular T cells and DCs, leading to augmentation of anti-tumor immunity.

[Animal experiments of immunotherapy with ovarian tumor vaccine during lymphopenia induced by chemotherapy.].

OBJECTIVE: To explore the mechanisms and effects of adoptive immunotherapy with ovarian cancer vaccine modified by GM-CSF gene which was used after immunologic reconstitution during lymphopenia induced by chemotherapy. METHODS: Lymphopenia was induced by chemotherapy with cyclophosphamide. The immune reconstituted model was built in rats. The tumor vaccine draining lymph nodes were harvested after the ovarian cancer cells NUTU-19 modified by GM-CSF gene were injected. The effector T cells (T(E)) were got after being stimulated and amplified. Enzyme-linked immunosorbent assay was used to detect the level of interleukin (IL)-2 and IL-4 secreted by T(E). Intracellular cytokine staining was used to determine frequency of tumor-specific T(E). Fluorescence-activated cell sorting (FACS) was used to detect the special cytotoxicity of T(E) killing target cells. The survival period of rats bearing pre-established abdominal ovariam carcinoma after being adoptively transferred by T(E) was observed. RESULTS: Compared with those in control group, the significant higher levels IL-2 [(65.7 +/- 4.0) pg/ml] and lower levels IL-4 [(277 +/- 49) pg/ml] were observed in chemotherapy-immune reconstitution-vaccine immunization group. The amount of CD(4)(+) T cells secreting interferon-gamma (13.0 +/- 2.1)% were also significantly increased. The rate of the special cytotoxicity of killing T cells (86.5 +/- 1.1)% was markedly improved. The survival period of rats (110 +/- 16) days was increased in chemotherapy-immune reconstitution-vaccine immunization group. CONCLUSIONS: The combined immunotherapy of chemotherapy-immune reconstitution-tumor vaccine immunotherapy may increase the frequency and function of specific tumor T(E). The specific cytotoxicity is increased and the weak reaction of T(E) to tumor is improved, which showed that this therapy can enhance immune reaction.

[The clinical observation on acupuncture at Xuanzhong (GB 39) and Ashi points for treatment of orthopedic postoperative pain].

OBJECTIVE: To compare the therapeutic effects between acupuncture and Bezoxazocine injection in treatment of orthopedic postoperative pain. METHODS: Sixty patients were randomly divided into an acupuncture group and a medication group, 30 cases in each group. The patients in the acupuncture group were treated by acupuncture at Xuanzhong (GB 39) as main point and Ashi points for 30 minutes; the medication group were treated by intramuscular injection of Bezoxazocine injection, 20 mg once, three times per day. Then the pain changes within 48 hours were observed and recorded in two groups. RESULTS: The good rates at 24 hours and 48 hours were 89.2% and 100.0% in the acupuncture group and 81.4% and 96.3% in the medication group, respectively. The analgesic effect of acupuncture was better than that of Bezoxazocine injection (P < 0.05). CONCLUSION: Analgesic effect of acupuncture at Xuanzhong (GB 39) on orthopedic postoperative pain and Ashi points is better than Bezoxazocine injection.