OBJECTIVE To explore the mechanism of Shenqi guben formula （SQGB） in improving cancer-related fatigue （CRF） based on network pharmacology and cellular experiments. METHODS Active components of SQGB and CRF-related targets were identified on the basis of databases such as the Traditional Chinese Medicine Systems Pharmacology platform. An in vitro CRF cell model was established by inducing A549 cells with interleukin-17 （IL-17）. Cells were treated with low （1.0 mg/mL） or high （1.5 mg/mL） concentrations of SQGB. The effects on cell viability， migration， apoptosis， inflammatory factors， mRNA expression， apoptosis-related proteins and key proteins 011） of IL-17 signaling pathway were evaluated using scratch assay， flow cytometry， ELISA， real-time fluorescent quantitative PCR and Western blot analysis. RESULTS SQGB contained 84 active components acting on 209 potential CRF targets. Among E-these， quercetin， kaempferol， and luteolin were identified as the core components of the compound. Core targets included tumor protein p53， AKT serine/threonine kinase 1， IL-6， and tumor necrosis factor （TNF）. IL-17， TNF and phosphatidylinositol-3- kinase-serine/threonine protein kinase （PI3K/Akt） signaling pathways were identified as crucial pathways. Compared with IL-17 intervention group， the cell migration rate， B-cell lymphoma 2 （Bcl-2） protein expression， the levels of IL-6 and TNF-α in the supernatant， mRNA expression of IL-17 receptor A （IL-17RA）， TNF-α， and IL-6， as well as the protein expression of IL-17RA and nuclear factor kappa-B p65 subunit （p65）， and phosphorylated （p）-p65/p65 ratio in IL-17+SQGB low- and high- quality concentration groups were all significantly decreased or down-regulation （P＜0.05）； the apoptosis rate， expression levels of Bcl-2 associated X protein （Bax） and cleaved caspase-3 protein， the ratio of Bax/Bcl-2， the expression level of p-p38 protein， and the p- p38/p38 ratio were all significantly increased or up-regulated （P＜0.05）. Moreover， the improvement effects of these indicators were mostly better in the high-quality concentration groups compared to the low-quality concentration groups （P＜0.05）. CONCLUSIONS SQGB ameliorates CRF by regulating the IL-17 signaling pathway， inhibiting the expression of inflammatory factors， and activating p38 MAPK-dependent apoptosis pathway.

Cancer multidrug resistance (MDR) impairs the therapeutic efficacy of various chemotherapeutics. Novel approaches, particularly the development of MDR reversal agents, are critically needed to address this challenge. This study demonstrates that tenacissoside I (TI), a compound isolated from Marsdenia tenacissima (Roxb.) Wight et Arn, traditionally used in clinical practice as an ethnic medicine for cancer treatment, exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells. TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin (DOX) and paclitaxel (PAC) by downregulating ABCB1 expression and reducing ABCB1 drug transport function. Mechanistically, protein arginine methyltransferase 1 (PRMT1), whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues, was differentially expressed in TI-treated SW620/AD300 cells. SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine (aDMA) and enhanced PRMT1-EGFR interaction compared to their parental cells. Moreover, TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR, PRMT1-EGFR interaction, and EGFR downstream signaling in SW620/AD300 and KBV200 cells. These effects were significantly reversed by PRMT1 overexpression. Additionally, TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities. This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR, suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
Humans ; Protein-Arginine N-Methyltransferases/antagonists & inhibitors* ; Drug Resistance, Neoplasm/drug effects* ; ErbB Receptors/genetics* ; Animals ; Cell Line, Tumor ; Drug Resistance, Multiple/drug effects* ; Methylation/drug effects* ; Saponins/administration & dosage* ; Mice ; Mice, Nude ; Mice, Inbred BALB C ; ATP Binding Cassette Transporter, Subfamily B/genetics* ; Doxorubicin/pharmacology* ; Paclitaxel/pharmacology* ; Female ; Repressor Proteins

Glutamate-ammonia ligase (GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer.

OBJECTIVE: To explore the clinical characteristics, diagnosis and surgical management of petrous bone cholesteatoma. METHOD: The data of 12 patients who underwent surgery for petrous bone cholesteatoma(PBC) were retrospectively analyzed with respects to the clinical characteristics, diagnosis and management. RESULT: Seven cases were characterized by a long otitis media history, severe hearing loss, and facial paralysis. In contrast, 5 cases were characterized with the symptoms of facial paralysis, hearing loss and vertigo attack and the absence of early otorrhea history. Trans labyrinth approach was chosen for 2 cases,while trans labyrinth-cochlear approach for 10. Cochlea was involved in 10 cases, while internal auditory canal in 9 and semicircular canal in 11. Otoscope was used in 1 case. Four patients were treated by partial resection of petrous apex and ear canal closure with good results. After years of follow-up, three recurrence cases were operated for a second time. Simultaneous facial nerve anastomosis or decompression was performed. The function of facial nerve recovered from V-VI to Ill-IV (House and Brackmann grading) in 6 anastomosis cases and from IV-V to II- IlI in 3 cases of decompression. CONCLUSION Petrous bone cholesteatoma was characterized by severe hearing loss, and facial paralysis. Surgical approaches are decided according to the extent of lesion and hearing status. Our study indicated that otoscope would help to ensure a radical removal of the pathology in cases with deep involvement and restricted vision. Partial resection of petrous bone and ear canal closure could be effective solution for challenging cerebrospinal fluid otorrhea with large dural defects and protecting vital neurovascular structures.
Adolescent ; Adult ; Child ; Child, Preschool ; Cholesteatoma ; diagnosis ; pathology ; surgery ; Female ; Humans ; Male ; Middle Aged ; Petrous Bone ; pathology ; surgery ; Retrospective Studies ; Young Adult

Objective: To explore the status of lymph node metastasis of middle third thoracic esophageal squamous cell carcinoma and its influence on the prognosis and to seek the reasonable range of lymphade-nectomy. Methods: A total of 129 patients who underwent curative esophagectomy with modern two-field lymphadenectomy of middle third thoracic esophageal squamous cell carcinoma were reviewed. Results: The lymph node metastasis rate was 56.6% and the upper mediastinal lymph node metastasis rate was 43.4%. The lymph node metastasis ratio (positive nodes/total dissected nodes, LMR) was 11.3%. Paraesophageal lymph nodes, lymph nodes near the right recurrent nerve, the left gastric and infracadnal lymph nodes were most commonly involved when the tumor was located in the middle thoracic esophagus. Tumor differentiation, the depth of tumor invasion and the length of tumor were influencing factors for lymph node metastasis. The 5-year survival of N_0, N_1 (LMR≤20%) and N_1 (LMR>20%) patients were 50.4%, 31.0% and 6.8%, respective-ly, with a significant difference among the three groups (P=0.000). Conclusion: LMR was one of the key fac-tors affecting the prognosis, of esophageal cancer. Patients with middle third thoracic esophageal carcinoma should be treated with radical surgery with modern two-field lymphadenectomy.

BACKGROUNDMost stage IIIB (T4/N3) non-small cell lung cancer (NSCLC) can not be cured via operation, but how is the outcome for those with T4 or occasionally N3 which can be completely resected? This paper retrospectively analyses the effects of the tumor characteristics and postoperative treatments on the survival of 51 patients with stage IIIB NSCLC completely resected in this hospital from January 1, 1997 to April 30, 2001.

METHODSThe effects of clinical pathophysiological characteristics such as gender, histological type, differentiation, T-stage and lymph node status and the postoperative chemotherapy or radiotherapy on the prognosis of 51 patients with completely resected stage IIIB NSCLC were retrospectively analysed.

RESULTSThere were no statistic survival differences in the disease characteristics such as the different gender (Log rank=0.992, P=0.319), histological types (Log rank=1.263, P=0.260), differentiation (Log rank=1.104, P=0.577), T-stage (Log rank=0.106, P=0.588) and lymph node status (Log rank=1.297, P=0.731), also no difference between groups whether or not there was postoperative mediastinal radiotherapy (Log rank=0.482, P=0.488) or postoperative chemotherapy (Log rank=0.051, P=0.759).

CONCLUSIONSNeither the tumor characteristics such as gender, histological type, differentiation, T-stage and N-stage, nor the postoperative mediastinal radiotherapy or chemotherapy affect the survival of stage IIIB NSCLC with complete resection.