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.

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.

Is high-frequency oscillatory ventilation more effective and safer than conventional protective ventilation in adult acute respiratory distress syndrome patients? A meta-analysis of randomized controlled trials.

INTRODUCTION: Comprehensively evaluating the efficacy and safety of high-frequency oscillatory ventilation (HFOV) is important to allow clinicians who are using or considering this intervention to make appropriate decisions. METHODS: To find randomized controlled trials (RCTs) comparing HFOV with conventional mechanical ventilation (CMV) as an initial treatment for adult ARDS patients, we searched electronic databases (including PubMed, MedLine, Springer Link, Elsevier Science Direct, ISI web of knowledge, and EMBASE) with the following terms: "acute respiratory distress syndrome", "acute lung injury", and "high frequency oscillation ventilation". Additional sources included reference lists from the identified primary studies and relevant meta-analyses. Two investigators independently screened articles and extracted data. Meta-analysis was conducted using random-effects models. RESULTS: We included 6 RCTs with a total of 1,608 patients in this meta-analysis. Compared with CMV, HFOV did not significantly reduce the mortality at 30 or 28 days. The pooled relative risk (RR) was 1.051 (95% confidence interval (CI) 0.813 to 1.358). ICU mortality was also not significantly reduced in HFOV group, with a pooled RR of 1.218 (95% CI 0.925 to 1.604). The pooled effect sizes of HFOV for oxygenation failure, ventilation failure and duration of mechanical ventilation were 0.557 (95% CI 0.351 to 0.884), 0.892 (95% CI 0.435 to 1.829) and 0.079 (95% CI -0.045 to 0.203), respectively. The risk of barotrauma and hypotension were similar between the CMV group and HFOV group, with a RR of 1.205 (95% CI 0.834 to 1.742) and a RR of 1.326 (95% CI 0.271 to 6.476), respectively. CONCLUSIONS: Although HFOV seems not to increase the risk of barotrauma or hypotension, and reduces the risk of oxygenation failure, it does not improve survival in adult acute respiratory distress syndrome patients.

[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.

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.

Safety of individual medication of Ma Qian Zi (semen strychni) based upon assessment of therapeutic effects of Guo's therapy against moderate fluorosis of bone.

OBJECTIVE: To assess the safety of individual medication of Guo's Ma Qian Decoction on the basis of effective treatment of fluorosis of bone with Guo's therapy. METHODS: One hundred and fourteen cases of moderate fluorosis of bone were randomly divided into a treatment group (n = 60) and a control group (n = 54) between December 2007 and August 2009 by using the block randomized method and a central random system. At the same time of basic treatment, the patients in the treatment group were orally administrated with Guo's Ma Qian Decoction. The initial dose of Ma Qian Zi (Semen Strychni) was 0.4 g and increased by 0.05 g every two days, with the doses of other drugs unchanged, until the patient had "nux vomica response". For the patients with no "nux vomica response", the dosage was continued to increase and the maximum dosage was not more than 1.2 g/day. The control group was treated with decoction placebo. The changes of strychnine and brucine contents before and after processing and after decoction of Ma Qian Zi (Semen Strychni) were determined with reversed-phase high-performance liquid chromatography, which were controlled within ranges stipulated in the Pharmacopeia; Adverse events were analyzed; Blood strychnine and brucine contents in 10 cases who had taken the drugs were determined. RESULTS: 1) Strychnine (2.125%) and brucine (1.425%) contents before processing of Ma Qian Zi and 1.88% and 1.31% after processing all conformed with the standards of strychnine (1.2-2.2%) and brucine (no less than 0.8%) stipulated in the Pharmacopeia. When the maximum dosage of Ma Qian Zi was 1.2 g/day, strychnine in the decoction was 11.17 mg and brucine was 7.44 mg, which all conformed with the maximum limited amount (strychnine 13.32 and brucine no less than 4.8 mg) stipulated in the Pharmacopeia. 2) Eight cases had "nux vomica response" in the treatment group and one case in the control group, with a significant difference between the two groups (P < 0.05). 3) Altogether 18 cases had adverse events, with an incidence rate of 15.38% (8 cases) in the treatment group and 18.52% (10 cases) in the control group, with no difference between the two groups (P > 0.05); Among them, 10 cases (8.77%) with the adverse event were not related with therapeutic drugs, with an incidence rate of 6.67% (4 cases) in the treatment and 11.11% (6 cases) in the control group, with no significant difference between the two groups (P > 0.05). Seven cases had suspicious relative adverse events, the risk in the treatment group was 0.658 times of the control group, with no significant difference (P > 0.05), and one case had the toxic reaction of nux-vomica seed. 4) Strychnine and brucine were unable to be detected in the blood in all points of time in the 10 cases who had taken the drugs, indicating that plasma strychnine and brucine contents were lower than the minimum detectable amount (10 ng), and accumulation of strychnine and brucine were not found in blood of the patient during and after administration for 8 weeks. CONCLUSION: The individual medication of Ma Qian Zi (Semen Strychni) in the Guo's therapy has a better safety.

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

OBJECTIVE: To explore clinical efficacy of percutaneous endoscopic lumbar discectomy through two different approaches in treating upper lumbar disc herniation. METHODS: From March 2015 to August 2019, 32 patients with upper lumbar disc herniation treated by percutaneous endoscopic lumbar dicecromy(PELD) were analyzed retrospectively and divided into percutaneous endoscopic transforaminal discectomy (PETD) and percutaneous endoscopic interlaminar discectomy (PEID) group according to different methods. There were 19 patients in PETD group, including 10 males and 9 females aged from 30 to 65 years old with an average of (44.70±12.08) years old;5 patients on L1, 2, 6 patients on L2, 3, 8 patients on L3, 4;6 patients were central herniation, 8 patients were paracentric herniation, and 5 patients were migration of herniation. There were 13 patients in PEID group, including 4 males and 9 females aged from 25 to 55 years old with an average of (42.23±12.09) years old;the courses of disease ranged from 1 to 7 months with an average of (2.90±3.02) months;3 patients on L1, 2, 4 patients on L2, 3, 6 patients on L3, 4;2 patients were central herniation, 4 patients were paracentric herniation, 3 patients were migration of herniation, 4 patients were prolapse free type protrusion. VAS and ODI score before operation, postoperative at 3 days, 3 and 6 months were compared between two groups, advanced MacNab standard at 1 year after operation were applied to evaluate clinical effects. RESULTS: Operation were successful operated in 32 patients and obtained following up without nerve injury and infection of intervertebral space. One patient in PETD groups occurred dural sac tear in operation, but no adverse reaction afteroperation. PETD group was followed up from 12 to 24 months with an average of (15.80±3.48) months, while PEID group was followed up from 12 to 30 months with an average of (16.70±4.66) months, while there was no statistical difference between two groups (P>0.05). VAS and ODI score at different time points after operation were higher than that of before operation (P<0.05). According to advanced MacNab standard at 1 year after operation, 11 patients obtained excellent results, 6 good, 1 moderate and 1 poor in PETD group;while 7 patients got excellent results, 4 good, 2 moderate in PEID group. CONCLUSION: Both of two surgical approach could achieve satisfactory efficacy in treating upper lumbar disc herniation, PETD is more suitable for central herniation, paracentric herniation and patients with mild displacement, PEID has advantage on prolapse free type protrusion.

[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.

[Preliminary analysis on X-ray in youth neck type of cervical spondylosis with upper crossed syndrome].

OBJECTIVE: To analyze the X-ray characteristics in youth neck type of cervical spondylosis with upper crossed syndrome(UCS). METHODS: The patients who had a neck type of cervical spondylosis with or without UCS were selected from January to October 2017, 20 cases in each group, and 10 normal volunteers were chosen in the study. X-ray examination of lateral and hyperextension-hyperflexion of cervical spine were performed to observe cervical spine angle, angular displacement and adjacent vertebral body slip. RESULTS: The cervical spine angle was (-0.40±9.64)° in the UCS group, significantly less than (14.35±9.01)° in the normal group and (12.34±5.65)° in the non-UCS group(P<0.05). The change of angular displacement of the upper cervical vertebra in anterior flexion and posterior extension was (8.18±4.81)° in UCS group, which was also significantly less than (12.14±3.48)° in the normal group and (12.34±5.65)° in the non-UCS group(P<0.05). The slippage of the vertebral posterior margin of the lower cervical spine in the anterior flexion was 15.41±2.21 in the UCS group, which was significantly greater than 13.26±2.42 in normal group(P<0.05), and was not obviously different from 15.64±2.07 in non-UCS group(P>0.05). CONCLUSIONS: In young patients who has a neck type of cervical spondylosis with UCS, the cervical curvature prone to straighten or reverse, the upper cervical flexion and extension are limited, while the lower cervical is in a flexion.

[Treatment of displacement-type lumbar intervertebral disc protrusion on L2-L5 with percutaneous endoscopic interlaminar discectomy].

OBJECTIVE: To evaluate the operative characteristic, safety, clinical effect of percutaneous endoscopic interlaminar discectomy (PEID) in treating displacement-type lumbar intervertebral disc protrusion on L2-L5. METHODS: Form November 2015 to October 2016, 15 patients with displacement-type lumbar intervertebral disc protrusion were treated with percutaneous endoscopic interlaminar discectomy. There were 9 males and 6 females, aged from 19 to 63 years old with an average of 42 years. All the patients with single-segment displacement-type lumbar intervertebral disc protrusion were diagnosed by clinical and iconography data, and complicated with low back pain and single lower limbs radioactivity pain. Lesion occurred in L4,5 of 8 cases, L3,4 of 4 cases, L2,3 of 3 cases. The patients were divided into 4 regions according to Lee standard (displaced nucleus pulposus location on spinal canal), I region was 2 cases, II region was 3 cases, III region was 5 cases, IV region was 5 cases.Preoperative, postoperative 3 months, final follow-up, lumbago-leg pain and lumbar function were assessed by VAS, JOA scores;at final follow-up, MacNab was used to evaluate the clinical effect;postoperative 3 months, rechecked lumbar MRI to observe discectomy condition. RESULTS: All the operations were successfully complete under local anesthesia, and no complications such as injuries of nerve root and dural sac, postoperative hemorrhage, local infection were found. Operative time was 45 to 90 min with an average of 54.8 min;and hospitalization time was 3 to 4 days with an average of 3 days. All 15 cases were followed up for 12 to 13 months with an average of 12.2 months, no recurrence was found. Preoperation, postoperative 3, 12 months, VAS scores were 8.2±1.4, 3.0±0.6, 1.7±0.5, JOA scores were 8.76±3.32, 23.61±2.14, 24.82±3.43, respectively. Postoperative VAS, JOA scores were obviously improved(P<0.05). According to MacNab standard to evaluate the clinical effect, 9 cases obtained excellent results, 5 good, 1 fair. CONCLUSIONS: PEID is a micro-trauma surgical method and has advantage of safe and effective in treating displacement-type lumbar intervertebral disc protrusion on L2-L5, but requires laminoplasty during operation, and under local anesthesia to operation maybe can induce neurostimulation.

[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.

Plasma long noncoding RNA IL-7R as a prognostic biomarker for clinical outcomes in patients with acute respiratory distress syndrome.

BACKGROUND: Long non-coding RNAs (lncRNAs) regulate a variety of genes and biological processes. Lnc-IL7R plays a considerable role in the regulation of inflammation, but its prognostic potential in acute respiratory distress syndrome (ARDS) has not been fully explained. In this study, the role of lnc-IL7R as a potential biomarker in ARDS was examined. OBJECTIVE: Role of lnc-IL7R as potential biomarker in ARDS. METHODS: LncRNA-IL7R was isolated from the plasma of patients with ARDS and healthy controls and clinical indexes were obtained within 24 h after admission. The relative expression of lnc-IL7R was obtained by quantitative real-time PCR. The correlations between lnc-IL7R and continuous variables in ARDS were tested using Spearman's coefficients. RESULTS: A total of 85 ARDS patients and 49 healthy controls were included. Plasma lnc-IL7R was significantly down-regulated in ARDS compared with the levels in healthy control individuals, especially in severe ARDS (P < .01). The area under the curve (AUC) of lnc-IL7R for ARDS diagnosis was 0.87 (sensitivity 75.3%, specificity 93.9%). The lnc-IL7R levels were correlated with the severity of ARDS (ρ = -0.31, P = .0215), oxygenation index (ρ = 0.61, P < .001), APACHE II score (ρ = -0.04, P = .0230), CRP (ρ = -0.26, P = .0148) and WBC (ρ = -0.29, P = .0064). Lnc-IL7R relative value ≥ 0.33 showed the lower 28-day mortality in the patients with ARDS(P < .05).The survivors showed higher lnc-IL7R level and lower APACHE II score, SOFA score and length of mechanical ventilation than in the non-survivors (P = .0109, P < .001, P < .001 and P = .017, respectively). CONCLUSIONS: Lnc-IL7R is a novel biomarker for the diagnosis of ARDS and predicts the severity of ARDS and 28-day mortality in this patients cohort. TRIAL REGISTRATION: The study was registered with the Chinese Clinical Trial Registry (ChiCTR-DOD-16008657).

[Percataneous endoscopic lumbar discectomy for the treatment of lumbar intervertebral disc protrusion].

OBJECTIVE: To explore the clinical effects of percataneous endoscopic lumbar discectomy for lumbar intervertebral disc protrusion. METHODS: The clinical data of 46 patients with lumbar intervertebral disc protrusion underwent percataneous endoscopic lumbar discectomy were retrospectively analyzed. There were 21 males and 25 females, aged from 23 to 65 years old with an average of 42 years. The course of disease was from 5 to 87 months with an average of 13.4 months. Protrusion located in L2,3 of 2 cases, L3,4 of 3 cases, L4,5 of 28 cases, L5S1 of 13 cases. There were 5 patients with central type, 34 with para-side type, 7 with extreme lateral type. VAS, ODI and JOA scores were used to analyze the condition of pain releasing and lumbar functional improvement. According to MacNab standard to evaluate the clinical effect at final follow-up. RESULTS: All the operations were successful, operative time was 125 to 210 min with a mean of 153.6 min; and all the patients were follow-up for 6 to 12 months with an average of 8 months; no injuries of nerve and blood vessel, infection were found. Postoperative 3 days and final follow-up, VAS score was 3.1±0.7, 2.2±0.6 respectively, and was obviously lower than preoperative 7.3±1.2(P<0.05). At final follow-up, JOA and ODI were (23.5±2.4) points, and (22.10±9.26)%, respectively, and was obviously improved compared with preoperative (13.2±2.8) points and (69.12±13.15)% (P<0.05). According to modified MacNab standard to evaluate the clinical outcome, 30 cases got excellent results, 14 good, 2 fair, no recurred and overhauling were found. CONCLUSIONS: Percataneous endoscopic lumbar discectomy is a minimally invasive technique, with advantage of safety and effectiveness, and apply to treatment of lumbar intervertebral disc protrusion.

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.

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.

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.

Low-Dose Ketamine Pretreatment Reduces the Incidence and Severity of Myoclonus Induced by Etomidate: A Randomized, Double-Blinded, Controlled Clinical Trial.

Myoclonic movement induced by etomidate is a common but undesirable problem during general anesthesia induction. To investigate the influence of pretreatment with low-dose ketamine on the incidence and severity of myoclonus induced by etomidate, 104 patients were randomized allocated to 1 of 2 equally sized groups (n = 52) to receive either intravenous low-dose ketamine 0.5 mg/kg (group K) or an equal volume of normal saline (group S) 1 minute before induction of anesthesia with 0.3-mg/kg etomidate. The incidence and severity of myoclonus were assessed for 2 minutes after administration of etomidate. Here, we found that the incidence and intensity of myoclonus were both significantly reduced in low-dose ketamine-treated group compared with saline-treated group. The incidence of adverse effects was low and similar between groups. These results demonstrate that intravenous infusion of low-dose ketamine 0.5 mg/kg 1 minute prior to etomidate administration is effective in relieving etomidate-induced myoclonic movements during general anesthesia induction.

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.