[Percutaneous foraminal endoscopy for the treatment of lumbar lateral recess stenosis in elderly].

OBJECTIVE: To investigate the clinical efficacy and safety of percutaneous foraminal endoscopy in the treatment of lumbar lateral recess stenosis in elderly. METHODS: The clinical data of 31 elderly patients with lumbar lateral recess stenosis treated by percutaneous foraminal endoscopic decompression from March 2018 to August 2019 were retrospectively analyzed. Including 16 males and 15 females, aged from 65 to 81 years with an average of (71.13±5.20) years, the course of disease ranged from 3 months to 7 years with an average of (14.36±6.52) months. Visual analogue scale (VAS) and Oswestry disability index (ODI) were used to assess clinical symptom and functional status before operation and 1, 6, 12 months after operation. At the final follow-up, the modified Macnab standard was used to evaluate clinical efficacy. RESULTS: All patients were completed the operation successfully. The operation time was from 75 to 120 min with an average of (97.84±11.22 ) min. All 31 patients were followed up from 12 to 28 months with an average of (17.29±5.56) months. Postoperative lumbago-leg pain VAS and ODI were significantly improved at 1, 6, and 12 months(P<0.01). At the final follow-up, according to the modified Macnab standard to evaluate the effect, 23 got excellent results, 5 good, 3 fair. One patient had severe adhesions between peripheral tissues and nerve root, and postoperative sensory abnormalities in the lower extremities were treated conservatively with traditional Chinese medicine and neurotrophic drugs, which recovered at 2 weeks after surgery. No complications such as nerve root injury and infection occurred. CONCLUSION: The intervertebral foraminal endoscopy technique, which is performed under local anesthesia for a short period of operation, ensures adequate decompression while minimizing complications, and is a safe and effective surgical procedure for elderly patients with lumbar lateral recess stenosis.

Mechanisms of cancer cell killing by metformin: a review on different cell death pathways.

Cancer resistance to anti-tumour agents has been one of the serious challenges in different types of cancer treatment. Usually, an increase in the cell death markers can predict a higher rate of survival among patients diagnosed with cancer. By increasing the regulation of survival genes, cancer cells can display a higher resistance to therapy through the suppression of anti-tumour immunity and inhibition of cell death signalling pathways. Administration of certain adjuvants may be useful in order to increase the therapeutic efficiency of anti-cancer therapy through the stimulation of different cell death pathways. Several studies have demonstrated that metformin, an antidiabetic drug with anti-cancer properties, amplifies cell death mechanisms, especially apoptosis in a broad-spectrum of cancer cells. Stimulation of the immune system by metformin has been shown to play a key role in the induction of cell death. It seems that the induction or suppression of different cell death mechanisms has a pivotal role in either sensitization or resistance of cancer cells to therapy. This review explains the cellular and molecular mechanisms of cell death following anticancer therapy. Then, we discuss the modulatory roles of metformin on different cancer cell death pathways including apoptosis, mitotic catastrophe, senescence, autophagy, ferroptosis and pyroptosis.

Acupuncture for Quality of Life in Gastric Cancer Patients Undergoing Adjuvant Chemotherapy.

CONTEXT: Patients with gastric cancer experience health-related quality of life (HRQOL) decline during adjuvant chemotherapy following gastrectomy. OBJECTIVES: This pilot study aimed to evaluate the preliminary effect and feasibility of electro-acupuncture (EA) for HRQOL and symptom burden in these patients. METHODS: In this open-label, multicenter, parallel controlled trial, gastric cancer patients who planned to receive adjuvant chemotherapy were randomly assigned to receive high-dose EA (seven times each chemotherapy cycle for three cycles), low-dose EA (three times each chemotherapy cycle), or usual care only. The acupoints prescription consisted of bilateral ST36, PC6, SP4, and DU20, EX-HN3, and selected Back-shu points. Patients completed the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) weekly, and the Edmonton Symptom Assessment System (ESAS). The primary outcome was the difference among the groups on the gastric cancer subscale (GaCS) of the FACT-Ga. RESULTS: Of the 66 randomized patients, 58 were analyzed according to intention-to-treat principle, and 45 were in the per-protocol set (PPS). The average scores in PPS of GaCS were 52.12±9.71, 51.85±12.36, and 45.37±8.61 in high-dose EA, low-dose EA, and control groups, respectively. EA was significantly associated with improved average GaCS scores when compared with control group (51.98±10.91 vs. 45.37±8.61, P = 0.039). EA treatment also produced ESAS relief at the end of intervention (14.36 ± 12.28 vs. 23.91 ± 15.52, P = 0.027). Participants in EA groups had fewer grade ≥3 leukopenia (0% vs. 15.79%, P = 0.031) and neutropenia (2.56% vs. 26.31%, P = 0.012). CONCLUSION: EA showed promising effects in improving HRQOL, controlling symptom burden, and reducing toxicity during adjuvant chemotherapy in gastric cancer patients. Future adequately powered trials are feasible and needed to confirm the specific effect of EA.

Helicobacter pylori infection is associated with the co-occurrence of bacteria in the oral cavity and the gastric mucosa.

BACKGROUND: Pathogens capable of impacting gastrointestinal tract tumor development are located in the oral cavity, but whether these oral bacteria are able to colonize the gastric mucosa in gastric cancer (GC) patients and whether Helicobacter pylori infection can influence this process remains to be established. METHODS: Microbial 16S rDNA deep sequencing was conducted to characterize bacteria present in paired gastric mucosa and tongue coating samples in 27 patients with superficial gastritis (SG) and 11 GC patients. RESULTS: While the overall composition of the gastric mucosa and tongue coating microbiomes differed substantially, certain bacteria were present in both of these communities. The co-occurrence of bacteria between the tongue coating and gastric mucosa differed significantly between SG and GC patients. Of the 15 most abundant shared oral bacteria genera (the core shared oral bacteria), which were associated with differences in microbiota composition between these tongue coating and gastric mucosa, three were enriched in the gastric mucosa of GC patients relative to SG patients, whereas, 12 were depleted in GC patient samples. Furthermore, the prevalence and relative abundance of these core shared oral bacteria in the gastric mucosa were also linked to H. pylori infection status, and the core shared oral bacteria were also associated with the overall composition of the gastric mucosal microbiome. CONCLUSIONS: Helicobacter pylori infections are linked to the co-occurrence of bacteria in the oral microbiome and the gastric mucosal microbiome. Ectopic colonization of oral microbes may be a primary driver of H. pylori-induced gastric microbial dysbiosis in patients with GC.

A Comparison of Tumor-Associated and Non-Tumor-Associated Gastric Microbiota in Gastric Cancer Patients.

BACKGROUND: How gastric cancer (GC) incidence is associated with changes in the gastric microbiome has not been firmly established. The present study therefore aims to investigate the microbial communities present within the gastric mucosa of patients with superficial gastritis (SG) or GC. METHODS: Paired tumor and paracancerous samples of the gastric mucosa were collected from 18 patients being surgically treated for GC and from 32 patients with SG being treated via gastroscopy. The gastric microbiome in these samples was then profiled via 16S rRNA sequencing, with a linear discriminant analysis effect size (LEfSe) approach used to identify and compare different bacteria, and with PICRUSt used for predictive functional analyses. RESULTS: GC patients exhibited a distinct gastric microbiota profile from that observed in SG patients. These changes were evident in both tumor and paracancerous tissues from GC patients. Specifically, we found that 6 bacterial genera were specifically enriched in GC tissue samples relative to SG samples, while 18 genera were depleted in these same samples. Based on the differential abundance of these bacteria, we were able to calculate microbial dysbiosis index (MDI) values, which were significantly higher in GC patients than in SG patients. In addition, MDI values were negatively correlated with gastric Shannon index and were positively correlated with relative Helicobacter spp. abundance. Importantly, these MDI values were readily able to discriminate between GC and SG patient samples. Functional analysis suggested that GC patients were more likely to harbor a nitrosating microbial community. CONCLUSIONS: GC patients exhibited a gastric microbiome profile distinct from that observed in SG patients, with these differences being evident in both tumor and paracancerous tissues. Differences in the relative abundance of Helicobacter spp. may be the primary driver of gastric dysbiosis in GC patients.

[Treatment of L4,5 lumbar disc herniation with percutaneous endoscopic lumbar discectomy through two different approaches].

OBJECTIVE: To analyze the clinical efficacy, indications and operative points of transforaminal approach and interlaminar approach in the treatment of L4,5 lumbar disc herniation. METHODS: A retrospective analysis was performed on 48 patients with L4,5 lumbar disc herniation treated by percutaneous endoscopic lumbar discectomy from November 2016 to June 2018. Among them, 32 patients underwent percutaneous endoscopic transforaminal discectomy(PETD), including 17 males and 15 females, with an average age of (60.22±16.55) years, and the course of disease was(2.18±2.68) months;16 patients underwent percutaneous endoscopic interlaminar discectomy(PEID), including 7 males and 9 females, with an average age of (42.25±15.89) years, and the course of disease was(2.90±3.02) months. VAS, ODI of two groups before operation, 3 days, 3 months, and 6 months after operation were analyzed, and modified Macnab standard was used to evaluate the clinical effects. RESULTS: All the 48 patients successfully completed the surgical treatment, and all patients were followed up. There was no significant difference in gender, course of disease and follow-up time between two groups (P>0.05). The age of PETD group was(60.22±16.55) years and PEID group was (42.25±15.89) years, there was statistical difference between two groups (P<0.05 ). In the PETD group, there were 10 patients with advanced age, non-free type(24 cases) was more than free type(8 cases), and shoulder type(27 cases) more than axillary type(1 case) and ventral type(4 cases). PETD was used in 5 patients with lateral type and 2 patients with extreme lateral type. In PEID group, the axillary type(8 cases) was more than the shoulder type(2 cases) and the ventral type(6 cases), PEID was used in 4 patients with high prolapse free type(I and IIregions). VAS scores and ODI of patients in two groups at each postoperative follow-up point were significantly improved compared with those before surgery(P<0.05). According to modified Macnab standard to evaluate the clinical effect, in PETD group, 24 cases obtained excellent results, 5 good, 2 fair, 1 poor, while in PEID group, 12 excellent, 3 good, 0 fair, 1 poor. CONCLUSIONS: Both two surgical approachs can achieve satisfactory efficacy in treating L4,5 lumbar disc herniation, but PETD is more suitable for elderly patients, non-free type, lateral type, extremely lateral type and shoulder type of lumbar disc herniation. High prolapse(I and II regions) and axillary type lumbar prominent should select PEID.

[Application of broad easy immediate surgery in percutaneous transforaminal endoscopic technology for lumbar lateral recess stenosis in the elderly].

OBJECTIVE: To explore the safety and effectiveness of percutaneous transforaminal endoscopic BEIS technology for lumbar lateral recess stenosis in the elderly. METHODS: From February 2014 to May 2016, 21 patients with lumbar lateral recess stenosis in elderly were treated with percutaneous endoscopic BEIS. There were 13 males and 8 females, aged from 70 to 85 years old with an average of 74.3 years. Preoperative, 1 and 12 months postoperative visual analogue scale(VAS) scores and Oswestry Disability Index(ODI) were statistically analyzed. MacNab was used to assess the clinical effects. RESULTS: All the operations were successful. The time ranged from 90 to 130 min with an average of 110 min. All the patients were followed up for 12 to 38 months with an average of 18 months. Preoperative, 1 and 12 months postoperative VAS scores were 8.47±1.23, 1.78±0.72, 0.68±0.32, and ODI scores were 32.48±10.03, 19.53±3.55, and 5.15±1.02, respectively. Postoperative scores of VAS and ODI were obviously improved(P<0.05). According to modified MacNab standard to evaluate the clinical effects, 14 cases obtained excellent results, 5 good, 2 fair. Lower limb paresthesia occurred in 1 case, and the condition was restored at 3 months postoperatively with conservative treatment. One patient was complicated with emphysema before operation secondary to pulmonary infection, and was effectively controlled with regulate antibiotic therapy. No infection of vertebral body or intervertebral space, no injuries of blood vessels or nerve root, no tear of dura, or the leakage of cerebrospinal fluid were found. CONCLUSIONS: Percutaneous transforaminal endoscopic BEIS is a safe and effective method for lumbar lateral recess stenosis in the elderly.

Identification of RING-box 2 as a potential target for combating colorectal cancer growth and metastasis.

Development of cancer metastasis is a key contributor to mortality in patients with colorectal cancer. High expression of RING-box 2 (RBX2) in cancer cells is known to play a key role in tumor progression. However, the role of RBX2 in colorectal cancer progression is not well elucidated. In this study, we silenced RBX2 via CRISPR/Cas9 in two colorectal cancer cell lines, HCT116 and SW480. RBX2 knockout attenuated proliferation, colony formation and enhanced sensitivity of colorectal cancer cells to paclitaxel treatment. Invasive property of HCT116 and SW480 cells was also attenuated by RBX2 silencing. We confirmed that increased RBX2 correlated with higher tumor cells growth and metastasis abilities by ectopic expression of RBX2 in HCT116 and SW480 cells. In vivo studies suggested that knockout of RBX2 inhibited xenografts growth and metastasis to lung tissue, whereas ectopic expression of RBX2 promoted these cellular functions. Mechanically, RBX2 induced gastric cancer cell growth and metastasis by activating mammalian target of rapamycin/S6 kinase 1 (mTOR/S6K1). Treatment of everolimus, the specific mTOR inhibitor, significantly attenuated RBX2-mediated cell proliferation and mobility in vitro. Taken together, these results revealed a novel role of RBX2 in colorectal cancer cell growth and metastasis via the mTOR pathway and suggested RBX2 may serve as a therapeutic target in colorectal cancer.

FOXQ1 promotes cancer metastasis by PI3K/AKT signaling regulation in colorectal carcinoma.

Colorectal cancer is one of the major health problems, with invade surrounding tissues, and migrate to distant organs being the most critical concern, thus identified metastasis associated hallmarks and more efficacious treatment are urgently needed. It found that forkhead box q1 (FOXQ1) is aberrant expression in variety of human cancers and FOXQ1 is involved in oncogenic pathways. However, the role of FOXQ1 has been unexplored in colorectal cancer metastasis to date. Here, expression of FOXQ1 was higher in colorectal cancer tissue samples and cancer cell lines than in normal colorectal tissue and cell lines. Further research suggested that FOXQ1 positively regulated cell proliferation in colorectal cancer and down-regulation of CDK6, extracellular regulated protein kinases 1/2 (ERK1/2) and mammalian target of rapamycin (mTOR). In corresponding to this result, over-expression of FOXQ1 significantly promoted colorectal cancer growth in vivo. Moreover, down regulation of FOXQ1 expression in colorectal carcinoma cell HCT116 and LOVO strikingly inhibits tumor growth in vivo. Finally, FOXQ1-dependent inhibition of colorectal cancer cell migration and invasion and down-regulation of focal adhesion kinase (FAK), phosphatidyl inositol 3-kinase (PI3K) phosphorylation, AKT (v-akt murine thymoma viral oncogene) phosphorylation and matrix metalloproteinase-2/9 (MMP-2/9) expression. These integrated efforts have identified FOXQ1 as a tumor promoter and might provide promising approaches for colorectal cancer metastasis treatment.

The pulmonary nodule "discovered" by pneumonia: a case report.

The number of patients diagnosed with pulmonary nodules increased as more patients with high risk of lung cancer choose low-dose computed tomography (CT) scans for the screening of cancer. Clinicians might get two questions from the patients: what is the definite diagnosis of the nodule? What should we do? We have already got many guidelines trying to solve these problems. There are also several prediction models for pulmonary nodules. However, guidelines are not suitable for all types of patients, and the reality of patients is more complicated. Here we reported a 58-year-old man with a lung nodule in the right upper lobe, which was occasionally found during a period of pneumonia. We suggested two periods of follow-up, and the patient was also admitted to a clinical trial about circulating tumor cells (CTCs). He finally accepted surgical excision with a pathologic diagnosis of adenocarcinoma. This case suggests that: we might suggest CT surveillance for patients with solid nodules about 8 mm maximum diameter; three-dimensional reconstruction of CT scans could provide more information about the details of nodules; CTCs counts of peripheral blood could be considered as a potential clue for malignancy.

Identification of HRAS as cancer-promoting gene in gastric carcinoma cell aggressiveness.

Gastric carcinoma is one of the most lethal malignancies of cancers and its prognosis remains dismal due to the paucity of effective therapeutic targets. Herein, we showed that HRAS is markedly up-regulated in gastric carcinoma. Prognostic analysis indicated that HRAS expression might be a prognostic indicator for the survival of patients with gastric carcinoma. Ectopic expression of HRAS in gastric carcinoma cells accelerated proliferation, migration, invasion, angiogenesis, and clone formation ability of gastric carcinoma cells in vitro. Furthermore, HRAS over-expressing significantly promoted the tumorigenicity of gastric carcinoma cells in vivo whereas silencing endogenous HRAS caused opposite outcomes. Moreover, we demonstrated that HRAS enhanced gastric carcinoma aggressiveness by activating VEGFA/PI3K/AKT pathway and Raf-1 signaling. Together, our results provide new evidence that HRAS overexpression promotes the progression of gastric carcinoma and might represent a novel therapeutic target for its treatment.

Formononetin, a novel FGFR2 inhibitor, potently inhibits angiogenesis and tumor growth in preclinical models.

Most anti-angiogenic therapies currently being evaluated in clinical trials target vascular endothelial growth factor (VEGF) pathway, however, the tumor vasculature can acquire resistance to VEGF-targeted therapy by shifting to other angiogenesis mechanisms. Therefore, other potential therapeutic agents that block non-VEGF angiogenic pathways need to be evaluated. Here we identified formononetin as a novel agent with potential anti-angiogenic and anti-cancer activities. Formononetin demonstrated inhibition of endothelial cell proliferation, migration, and tube formation in response to basic fibroblast growth factor 2 (FGF2). In ex vivo and in vivo angiogenesis assays, formononetin suppressed FGF2-induced microvessel sprouting of rat aortic rings and angiogenesis. To understand the underlying molecular basis, we examined the effects of formononetin on different molecular components in treated endothelial cell, and found that formononetin suppressed FGF2-triggered activation of FGFR2 and protein kinase B (Akt) signaling. Moreover, formononetin directly inhibited proliferation and blocked the oncogenic signaling pathways in breast cancer cell. In vivo, using xenograft models of breast cancer, formononetin showed growth-inhibitory activity associated with inhibition of tumor angiogenesis. Moreover, formononetin enhanced the effect of VEGFR2 inhibitor sunitinib on tumor growth inhibition. Taken together, our results indicate that formononetin targets the FGFR2-mediated Akt signaling pathway, leading to the suppression of tumor growth and angiogenesis.

Association of the metformin with the risk of lung cancer: a meta-analysis.

OBJECTIVE: To assess the correlation between metformin and risk of developing lung cancer by meta-analysis. METHODS: Papers on the correlation between metformin and risk of lung cancer were searched from PubMed, MEDLINE, EMBASE, ISI Web of Science, and Cochrane Library. RESULTS: Six papers on case-control study were included in this study, involving 39,787 metformin users and 177,752 controls. Meta-analysis showed that the risk of developing lung cancer was lower in metformin users than in those without metformin (OR=0.55, 95% CI: 0.35-0.85, P<0.001). CONCLUSIONS: The risk of developing lung cancer is lower in metformin users than in those without metformin.