Impact of high-altitude acclimatization and de-acclimatization on the intestinal microbiota of rats in a natural high-altitude environment.

Introduction: Intestinal microorganisms play an important role in the health of both humans and animals, with their composition being influenced by changes in the host's environment. Methods: We evaluated the longitudinal changes in the fecal microbial community of rats at different altitudes across various time points. Rats were airlifted to high altitude (3,650 m) and acclimatized for 42 days (HAC), before being by airlifted back to low altitude (500 m) and de-acclimatized for 28 days (HADA); meanwhile, the control group included rats living at low altitude (500 m; LA). We investigated changes in the gut microbiota at 12 time points during high-altitude acclimatization and de-acclimatization, employing 16S rRNA gene sequencing technology alongside physiological indices, such as weight and daily autonomous activity time. Results: A significant increase in the Chao1 index was observed on day 14 in the HAC and HADA groups compared to that in the LA group, indicating clear differences in species richness. Moreover, the principal coordinate analysis revealed that the bacterial community structures of HAC and HADA differed from those in LA. Long-term high-altitude acclimatization and de- acclimatization resulted in the reduced abundance of the probiotic Lactobacillus. Altitude and age significantly influenced intestinal microbiota composition, with changes in ambient oxygen content and atmospheric partial pressure being considered key causal factors of altitude-dependent alterations in microbiota composition. High-altitude may be linked to an increase in anaerobic bacterial abundance and a decrease in non-anaerobic bacterial abundance. Discussion: In this study, the hypobaric hypoxic conditions at high-altitude increased the abundance of anaerobes, while reducing the abundance of probiotics; these changes in bacterial community structure may, ultimately, affect host health. Overall, gaining a comprehensive understanding of the intestinal microbiota alterations during high-altitude acclimatization and de-acclimatization is essential for the development of effective prevention and treatment strategies to better protect the health of individuals traveling between high- and low-altitude areas.

MiR-519a functions as a tumor suppressor and is negatively associated with poor prognosis of non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the major type of lung cancer. MicroRNAs (miRNAs) are currently considered as novel targets and tools in cancer therapy. OBJECTIVE: The aim of this study was to investigate the expression level and functional role of miR-519a in NSCLC, as well as its clinical values. METHODS: One hundred and two patients with NSCLC were recruited. Quantitative real-time PCR (qRT-PCR) was used for the measurement of the expression level of miR-519a. Kaplan-Meier survival and Cox regression analyses were conducted to explore the prognostic significance of miR-519a in NSCLC. MTT and Transwell assays were used to detect the effect of miR-519a on NSCLC cell proliferation, migration, and invasion. RESULTS: MiR-519a was significantly downregulated in NSCLC tissues, as well as NSCLC cell lines. The expression level of miR-519a was prominently associated with lymph node metastasis and TNM stage. Kaplan-Meier analysis suggested that low miR-519a expression was closely associated with shorter overall survival. Multivariate Cox regression analysis demonstrated that miR-519a expression level and TNM stage were two independent prognostic factors for 5-year overall survival in NSCLC patients. In vitro study, miR-519a significantly inhibited the proliferation, migration, and invasion of NSCLC cells. STAT3 was proved to be the target gene of miR-519a. CONCLUSIONS: MiR-519a functions as a tumor suppressor and inhibits tumor progression of NSCLC via targeting STAT3. MiR-519a may act as a prognostic biomarker and therapeutic target for NSCLC.

Overexpression of miR-425-5p is associated with poor prognosis and tumor progression in non-small cell lung cancer.

BACKGROUND: MicroRNA-425-5p (miR-425-5p) has been investigated in some human cancers, but the understanding of its clinical and functional roles in non-small cell lung cancer (NSCLC) remains poor. OBJECTIVE: This study sought to measure the expression of miR-425-5p in NSCLC samples, assess its prognostic significance in cancer patients, and explore its functional role during tumor progression. METHODS: Expression of miR-425-5p was examined using quantitative Real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier survival analysis and Cox analysis were conducted to evaluate the prognostic value of miR-425-5p. The effects of miR-425-5p on NSCLC cell proliferation, migration and invasion were assessed using cell experiments. RESULTS: Expression of miR-425-5p was upregulated in NSCLC tissues and cells compared with the normal controls (all P< 0.05). The increased miR-425-5p expression was associated with positive lymph node metastasis and TNM advanced stage of the patients (all P< 0.05). The survival curves and Cox analysis indicated that high miR-425-5p was correlated with poor overall survival and acted as an independent prognostic factor in NSCLC patients. Cell experiments suggested that miR-425-5p overexpression could enhance, whereas its reduction could suppress NSCLC cell proliferation, migration and invasion (all P< 0.05). Forhead box J3 (FOXJ3) was proved to be a direct target of miR-425-5p in NSCLC. CONCLUSIONS: Overexpression of miR-425-5p predicts poor prognosis of NSCLC and promotes cancer cell proliferation, migration and invasion by targeting FOXJ3.

Khubchandani's procedure combined with stapled posterior rectal wall resection for rectocele.

BACKGROUND: Obstructed defecation syndrome (ODS) is a widespread disease in the world. Rectocele is the most common cause of ODS in females. Multiple procedures have been performed to treat rectocele and no procedure has been accepted as the gold-standard procedure. Stapled transanal rectal resection (STARR) has been widely used. However, there are still some disadvantages in this procedure and its effectiveness in anterior wall repair is doubtful. Therefore, new procedures are expected to further improve the treatment of rectocele. AIM: To evaluate the efficacy and safety of a novel rectocele repair combining Khubchandani's procedure with stapled posterior rectal wall resection. METHODS: A cohort of 93 patients were recruited in our randomized clinical trial and were divided into two different groups in a randomized manner. Forty-two patients (group A) underwent Khubchandani's procedure with stapled posterior rectal wall resection and 51 patients (group B) underwent the STARR procedure. Follow-up was performed at 1, 3, 6, and 12 mo after the operation. Preoperative and postoperative ODS scores and depth of rectocele, postoperative complications, blood loss, and hospital stay of each patient were documented. All data were analyzed statistically to evaluate the efficiency and safety of our procedure. RESULTS: In group A, 42 patients underwent Khubchandani's procedure with stapled posterior rectal wall resection and 34 were followed until the final analysis. In group B, 51 patients underwent the STARR procedure and 37 were followed until the final analysis. Mean operative duration was 41.47 ± 6.43 min (group A) vs 39.24 ± 6.53 min (group B). Mean hospital stay was 3.15 ± 0.70 d (group A) vs 3.14 ± 0.54 d (group B). Mean blood loss was 10.91 ± 2.52 mL (group A) vs 10.14 ± 1.86 mL (group B). Mean ODS score in group A declined from 16.50 ± 2.06 before operation to 5.06 ± 1.07 one year after the operation, whereas in group B it was 17.11 ± 2.57 before operation and 6.03 ± 2.63 one year after the operation. Mean depth of rectocele decreased from 4.32 ± 0.96 cm (group A) vs 4.18 ± 0.95 cm (group B) preoperatively to 1.19 ± 0.43 cm (group A) vs 1.54 ± 0.82 cm (group B) one year after operation. No other serious complications, such as rectovaginal fistula, perianal sepsis, or deaths, were recorded. After 12 mo of follow-up, 30 patients' (30/34, 88.2%) final outcomes were judged as effective and 4 (4/34, 11.8%) as moderate in group A, whereas in group B, 30 (30/37, 81.1%) patients' outcomes were judged as effective, 5 (5/37, 13.5%) as moderate, and 2 (2/37, 5.4%) as poor. CONCLUSION: Khubchandani's procedure combined with stapled posterior rectal wall resection is an effective, feasible, and safe procedure with minor trauma to rectocele.