Babao Dan alleviates gut immune and microbiota disorders while impacting the TLR4/MyD88/NF-кB pathway to attenuate 5-Fluorouracil-induced intestinal injury.

Adjuvant chemotherapy based on 5-fluorouracil (5-FU), such as FOLFOX, is suggested as a treatment for gastrointestinal cancer. Yet, intestinal damage continues to be a prevalent side effect for which there are no practical prevention measures. We investigated whether Babao Dan (BBD), a Traditional Chinese Medicine, protects against intestinal damage induced by 5-FU by controlling immune response and gut microbiota. 5-FU was injected intraperitoneally to establish the mice model, then 250 mg/kg BBD was gavaged for five days straight. 5-FU led to marked weight loss, diarrhea, fecal blood, and histopathologic intestinal damage. Administration of BBD reduced these symptoms, inhibited proinflammatory cytokine (IL-6, IL-1ß, IFN-γ, TNF-α) secretion, and upregulated the ratio of CD3(+) T cells and the CD4(+)/CD8(+) ratio. According to 16S rRNA sequencing, BBD dramatically repaired the disruption of the gut microbiota caused in a time-dependent way, and increased the Firmicutes/Bacteroidetes (F/B) ratio. Transcriptomic results showed that the mechanism is mainly concentrated on the NF-κB pathway, and we found that BBD reduced the concentration of LPS in the fecal suspension and serum, and inhibited TLR4/MyD88/NF-κB pathway activation. Furthermore, at the genus level on the fifth day, BBD upregulated the abundance of unidentified_Corynebacteriaceae, Aerococcus, Blautia, Jeotgalicoccus, Odoribacter, Roseburia, Rikenella, Intestinimonas, unidentified_Lachnospiraceae, Enterorhabdus, Ruminiclostridium, and downregulated the abundance of Bacteroides, Parabacteroides, Parasutterella, Erysipelatoclostridium, which were highly correlated with intestinal injury or the TLR4/MyD88/NF-κB pathway. In conclusion, we established a network involving 5-FU, BBD, the immune response, gut microbiota, and key pathways to explain the pharmacology of oral BBD in preventing 5-FU-induced intestinal injury.

[Pharyngocutaneous fistula following total laryngectomy in patients with advanced stage hypopharyngeal or laryngeal carcinomas].

OBJECTIVE: To investigate the locations, predisposing factors, managements and outcomes of pharyngocutaneous fistula (PCF) following total laryngectomy in patients with advanced stage hypopharyngeal or laryngeal carcinomas. METHOD: One hundred and ninety-eight patients with advanced hypopharyngeal or laryngeal carcinomas who were performed by total laryngectomy were analyzed retrospectively. The multiple predisposing factors, including age, sex, preoperative radiotherapy, previous tracheostomy, stage, differentiation, site, neck dissection and postoperative fever, were analyzed. RESULT: The incidence of PCF was 16.7%. The situations of orificium fistulae lied in 69.7% superior segment, 21.2% inferior and 9.1% middle segment respectively. The incidence of PCF was 24.7% in hypopharynx and 11.6% in larynx respectively. There were significant differences between them. The differences of postoperative continuous fever beyond 5 days were statistical significance between the group of PCF and no PCF. In them, 28 patients of PCF were healed spontaneously and 5 of them were healed by surgical operation. CONCLUSION: PCF is often situated in tongue base and post-superior of trachea stoma. Tumor locations and postoperative fever are important predisposition.

[Laryngeal functional reconstruction with pedunculated musculocutaneous flap of platysma after partial laryngectomy].

OBJECTIVE: To explore the value of laryngeal functional reconstruction with pedunculated musculocutaneous flap of platysma after partial laryngectomy. METHOD: Fifty-four cases with glottic carcinoma were operated by partial or enlarged partial laryngectomy, and reconstructed laryngeal function with pedunculated musculocutaneous flap of platysma. RESULT: All the cases regained the swallow, vocalization and breath. The rate of extubation was 100%, and the 5-year survival rate was 92.59%. CONCLUSION: Application of pedunculated musculocutaneous flap of platysma to reconstruct laryngeal function is one of the effective method after partial laryngectomy.

[Massive concha bullosa pyocele with orbital extension--a case report and review of the literature].

OBJECTIVE: To discuss the complication of common anatomic variant of the middle turbinate-concha bullosa. METHOD: We present a 35 years old man with inner canthus proptosis and orbital pain who was diagnosed to be a pyocele originated from concha bullosa by CT and operation. RESULT: Concha bullosa can develop to a pyocele. Direct extension of the mass from the nose into the orbit may occur. Good therapeutic effect was obtained by endoscopic operation. CONCLUSION: Concha bullosa can result in obstruction of middle meatus and lead to sinusitis. Polyps or mucocele may also occur to Concha bullosa itself. Pyocele of concha bullosa can develop to such a massive extent that it leads to orbital complication. Endoscopic operation is best treatment to this disease.

[Establishment of a HPV-negative cell line derived from xenografted human laryngeal squamous cell carcinoma].

OBJECTIVE: To establish a human laryngeal carcinoma cell line unassociated with human papillomavirus (HPV). METHODS: Viable tissue of a well-differentiated laryngeal squamous cell carcinoma was obtained and tested negative for the presence of HPV by polymerase chain reaction. Minced tissue fragments were then transplanted subcutaneously into nude mice. After two successive passages, the tumor tissue was seeded into culture flasks and incubated in a medium containing 10% fetal bovine serum, insulin and epidermal growth factor. Tumor cell phenotype and molecular features were determined by various methods. RESULTS: A stable cell line, designated as Lscc-02, was successfully established after 86 culture passages. The cells grew as a monolayer with epithelioid features. The cell doubling time was approximately 39.1 hours. The human origin of the tumor cells was confirmed by karyotype analysis. The squamous epithelial phenotype was demonstrated by the immunopositivity of anti-cytokeratin antibodies and ultrastructural presence of tonofilaments and desmosomes. The malignant nature of the cells was documented by their clonal formation in soft-agar and tumorigenicity in nude mice. Lscc-02 cells expressed carcinoembryonic antigen (CEA) and were negative for HPV DNA. CONCLUSION: This newly established Lscc-02 laryngeal squamous cell carcinoma cell line may be a useful model for investigating laryngeal carcinoma unrelated to HPV infection, and the role of HPV in the progression of human laryngeal carcinoma.

[Influence of RNA interference targeting against human telomerase reverse transcriptase on expression of C-myc protein].

OBJECTIVE: To investigate the effect of inhibiting human telomerase reverse transcriptase (hTERT) on expression of C-myc protein by RNA interference (RNAi) in the larynx cancer cell line, Hep-2. METHOD: The primary structures of hTERT cDNA were found in GeneBank. Then the structure analyses were done according to the strategy of RNAi, which determined the specific base sequences to design shRNA plasmid. One type of plasmid, pshRNA1, involved in fluorescein gene was synthesized based on the specific base sequence. Control pshRNA2-a random sequence-were also constructed. METAFECTENE was used as the transfect ion reagent. Cells were treated daily with pshRNA1-2 or normal culture medium respectively. After administration of pshRNA1-2, hTERT mRNA was detected by RT-PCR, hTERT protein and C-myc protein were examined by Western Blot. RESULT: The expression of hTERT mRNA and protein were both significantly decreased after treated by pshRNA1 (P < 0.05). The expression of C-myc protein was significantly increased after treated by pshRNA1 (P < 0.01). CONCLUSION: The inhibition of hTERT expression could increase the expression of C-myc protein in Hep-2 cells.