The lncRNA20718-miR6022-RLPs module regulates tomato resistance to Phytophthora infestans.

KEY MESSAGE: Sl-lncRNA20718 acts as an eTM of Sl-miR6022 regulating its expression thereby affecting SlRLP6/10 expression. SlRLP6/10 regulate PRs expression, ROS accumulation, and JA/ET content thereby affecting tomato resistance to P. infestans. Tomato (Solanum lycopersicum) is an important horticultural and cash crop whose yield and quality can be severely affected by Phytophthora infestans (P. infestans). Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are widely involved in plant defense responses against pathogens. The involvement of Sl-lncRNA20718 and Sl-miR6022 in tomato resistance to P. infestans as well as the targeting of Sl-miR6022 to receptor-like protein genes (RLPs) were predicted in our previous study. However, uncertainty exists regarding their potential interaction as well as the molecular processes regulating tomato resistance. Here, we found that Sl-lncRNA20718 and Sl-miR6022 are positive and negative regulators of tomato resistance to P. infestans by gain- and loss-of-function experiments, respectively. Overexpression of Sl-lncRNA20718 decreased the expression of Sl-miR6022, induced the expression of PRs, reduced the diameter of lesions (DOLs), thereby enhanced disease resistance. A six-point mutation in the binding region of Sl-lncRNA20718 to Sl-miR6022 disabled the interaction, indicating that Sl-lncRNA20718 acts as an endogenous target mimic (eTM) of Sl-miR6022. We demonstrated that Sl-miR6022 cleaves SlRLP6/10. Overexpression of Sl-miR6022 decreases the expression levels of SlRLP6/10, induces the accumulation of reactive oxygen species (ROS) and reduces the content of JA and ET, thus inhibiting tomato resistance to P. infestans. In conclusion, our study provides detailed information on the lncRNA20718-miR6022-RLPs module regulating tomato resistance to P. infestans by affecting the expression of disease resistance-related genes, the accumulation of ROS and the phytohormone levels, providing a new reference for tomato disease resistance breeding.

Combined Transplantation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Restores Cavernous Nerve Injury-Related Erectile Dysfunction.

BACKGROUND: Whether combined transplantation of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) is more effective than transplantation of a single cell type in the restoration of erectile function is unknown. AIM: To investigate the effect of combined transplantation of MSCs and EPCs on restoration of erectile function in rats with cavernous nerve injury (CNI). METHODS: MSCs were isolated from human bone marrow and EPCs were isolated from human umbilical cord blood. MSCs and EPCs were identified by flow cytometry and in vitro differentiation or immunofluorescence staining. 25 8-week-old male Sprague-Dawley rats were allocated to 1 of 5 groups: sham operation group, bilateral CNI group receiving periprostatic implantation of MSCs plus EPCs, MSCs, EPCs, or phosphate buffered saline (control group). 2 weeks after CNI and treatment, erectile function of rats was measured by electrically stimulating the CN. The penis and major pelvic ganglia were harvested for histologic examinations. RNA and protein levels of neurotrophin factors (vascular endothelial growth factor, nerve growth factor, and brain-derived neurotrophic factor) in mono- or coculture MSCs and EPCs were assessed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. OUTCOMES: Intracavernous pressure and mean arterial pressure were measured to evaluate erectile function. Histologic examinations of the penis and major pelvic ganglia and RNA and protein levels of neurotrophin factors in MSCs and EPCs were performed. RESULTS: MSCs and EPCs expressed the specified cell markers and exhibited the typical appearance and characteristics. Treatments using MSCs and/or EPCs could increase endothelial and smooth muscle contents of the corpus cavernosum, decrease caspase-3 expression and increase penile neuronal nitric oxide synthase expression, and restore the neural component of the major pelvic ganglia in rats with CNI. Combined transplantation of MSCs and EPCs had a better effect on improving erectile function than single transplantation of MSCs or EPCs. Expression levels of vascular endothelial growth factor and nerve growth factor in coculture MSCs and EPCs were significantly higher than those of primary MSCs or EPCs. CLINICAL TRANSLATION: Combined transplantation of MSCs and EPCs was more effective in restoring erectile function in CNI-related erectile dysfunction models. STRENGTHS AND LIMITATIONS: The study, for the 1st time, proved that combined transplantation of MSCs and EPCs was more effective in restoring erectile function in rats with CNI. The rat model might not represent the human condition. CONCLUSION: Combined periprostatic transplantation of MSCs and EPCs could restore erectile function in rats with CNI more effectively. MSCs might restore CN fibers by secreting neurotrophin factors such as vascular endothelial growth factor and nerve growth factor, and EPCs could enhance the paracrine activity of MSCs. Fang J-f, Huang X-n, Han X-y, et al. Combined Transplantation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Restores Cavernous Nerve Injury-Related Erectile Dysfunction. J Sex Med 2018;15:284-295.

Laparoscopic resection for rectal cancer and cholecystectomy for patient with situs inversus totalis.

Situs inversus totalis (SIT) is a rare congenital anomaly presenting with complete transposition of thoracic and abdominal viscera. Laparoscopic surgery for either rectal cancer or gallbladder diseases with SIT is rarely reported in the literature. A 39-year-old woman was admitted to hospital owing to rectal cancer. She was diagnosed with SIT by performing radiography and abdominal computed tomography scan as a routine preoperative investigation. We performed laparoscopic resection for rectal cancer successfully in spite of technical difficulties caused by abnormal anatomy. One year later, she was diagnosed with cholecysticpolyp, and we performed laparoscopic cholecystectomy for her uneventfully. With this case, we believe that performance by an experienced laparoscopic surgeon, either laparoscopic resection for rectal cancer or cholecystectomy with SIT is safe and feasible.

Laparoscopic lysis of the ligament of treitz for superior mesenteric artery syndrome.

BACKGROUND: Superior mesenteric artery (SMA) syndrome (SMAS) is a rare condition caused by compression of the third portion of the duodenum by the SMA. The effect of the laparoscopic management of SMAS remains poorly understood. This study aimed to investigate the feasibility and effect of the laparoscopic management for SMAS. METHODS: We retrospectively reviewed 19 cases of SMAS who underwent surgical interventions in The Third Affiliated Hospital of Sun Yat-sen University between June 2006 and October 2013, consisting of 8 cases of duodenojejunostomy (DJ) and 11 cases of laparoscopic lysis of the ligament of Treitz (LL-LOT). A telephone survey was conducted to collect the follow-up status. RESULTS: Either DJ or LL-LOT was performed smoothly. The median operative time of the laparoscopic procedure and DJ was 56 and 95 min, respectively. Median blood loss was 10 versus 35 ml. Median postoperative hospital stays in both were 8 days. Ten cases of the laparoscopic group recovered uneventfully, while 1 case still presented symptoms of abdominal distention. Upper gastrointestinal fluoroscopy showed marked 'to-and-fro' peristalsis. An additional DJ was performed 35 days later to resolve her symptoms. CONCLUSIONS: LL-LOT is simple, feasible, minimally invasive and effective for SMAS with no severe duodenum 'to-and-fro' peristalsis.

Antioxidant lignans from the roots of Vladimiria muliensis.

Three new lignans (1, 2, and 8) and ten known ones (3-7, 9-13) were isolated from the roots of Vladimiria muliensis. Their structures and configurations were elucidated by means of spectroscopic techniques (IR, MS, NMR, and CD) and chemical methods. The isolated compounds were evaluated for their antioxidant and antibacterial activities. The antioxidant activity was the greatest for lignans 7 and 10 with IC50 values of 11.2 and 7.3 µM against DPPH radical, and of 1.6 and 1.7 µM against ABTS+ radical, respectively. Moreover, 7 also displayed broad-spectrum antibacterial activity with MIC values around 7.25 µg/mL.

[Surgical treatment for endoscopically unresectable polyps of colon and rectum].

OBJECTIVE: To explore the characteristics and risks of cancer in endoscopically unresectable polyps and compare the surgical outcomes of different operations. METHODS: A retrospective review of 40 patients undergoing surgical operations for polyps unresectable at colonoscopy between August 2006 and July 2012 from Department of Gastrointestinal Surgery was performed. The follow-up period was 3 to 72 months (median: 24.5 months). RESULTS: The rate of endoscopically unresectable polyps with invasive cancer was 67.5% (27/40). And it was significantly influenced by patient age and number of polyps (both P < 0.01). Perioperative volume of blood loss ((86 ± 58) ml vs (44 ± 32) ml, P = 0.0066), time to first flatus ((2.7 ± 1.3) d vs (1.7 ± 0.6) d, P = 0.0018), incidence of complication (2 cases vs 0, P = 0.0365) and hospital stay ((11.2 ± 1.0) d vs (15.0 ± 5.0) d, P = 0.0164) were significantly different between open colectomy and laparoscopic group. And the long-term survival outcomes were similar in both groups (90.9% (10/11) vs 100.0% (27/27), 90.9% (10/11) vs 96.3% (26/27), both P > 0.05). CONCLUSIONS: Endoscopically unresectable polyps of colon and rectum have high malignancy rate. Polyps in elderly patients and multiple polyps are more likely to develop invasive cancer. Long-term outcomes are similar between open colectomy and laparoscopic colectomy groups, but laparoscopic group has better short-term outcomes. For endoscopically unresectable polyps, laparoscopic colectomy may be the first choice.

A digital workflow to predict facial aesthetics in patients with maxillofacial trauma with implant retained prostheses.

Purpose To introduce a digital workflow for the prediction of facial aesthetics, especially in patients with dentation deformity caused by maxillofacial trauma.Methods Cone-beam computed tomography (CBCT) and three-dimensional facial scans of patients with radiographic prostheses were collected. The aforementioned data were uploaded to ProPlan CMF software and merged to generate a virtual patient with craniofacial hard tissue, realistic facial soft tissue, and remaining dentition. The radiographic prostheses were scanned to form a digital cast, which was fitted with its CBCT image to create the virtual prostheses. Postoperative facial soft tissue was simulated according to the movement of the virtual prostheses. An appropriate virtual diagnostic prosthesis plan was selected by the patient and dentist. Subsequently, prosthetically driven implant guide and restoration were designed and fabricated.Conclusions A virtual patient was successfully constructed. A 4-mm protrusion of the virtual prosthesis was chosen. Subsequently, implant surgery was performed, and dental prostheses were fabricated based on this location. The fusion of the postoperative facial scan and preoperative facial prediction was found to be coincident. This technique can effectively predict facial aesthetic features of patients with maxillofacial trauma, facilitate communication with patients, reduce chairside time, and guide the multidisciplinary design of implant placement and restoration fabrication.

Incidence, prevention, risk factors, and prediction of venous thromboembolism in Chinese patients after colorectal cancer surgery: a prospective, multicenter cohort study.

BACKGROUND: Venous thromboembolism (VTE) is a common and serious complication after colorectal cancer (CRC) surgery. Few large-sample studies have reported VTE incidence and management status after CRC surgery in China. This study aimed to investigate the incidence and prevention of VTE in Chinese patients after CRC surgery, identify risk factors for developing VTE, and construct a new scoring system for clinical decision-making and care planning. METHODS: Participants were recruited from 46 centers in 17 provinces in China. Patients were followed up for 1 month postoperatively. The study period was from May 2021 to May 2022. The Caprini score risk stratification and VTE prevention and incidence were recorded. The predictors of the occurrence of VTE after surgery were identified by multivariate logistic regression analysis, and a prediction model (CRC-VTE score) was developed. RESULTS: A total of 1836 patients were analyzed. The postoperative Caprini scores ranged from 1 to 16 points, with a median of 6 points. Of these, 10.1% were classified as low risk (0-2 points), 7.4% as moderate risk (3-4 points), and 82.5% as high risk (≥5 points). Among these patients, 1210 (65.9%) received pharmacological prophylaxis, and 1061 (57.8%) received mechanical prophylaxis. The incidence of short-term VTE events after CRC surgery was 11.2% (95% CI 9.8-12.7), including deep venous thrombosis (DVT) (11.0%, 95% CI 9.6-12.5) and pulmonary embolism (PE) (0.2%, 95% CI 0-0.5). Multifactorial analysis showed that age (≥70 years), history of varicose veins in the lower extremities, cardiac insufficiency, female sex, preoperative bowel obstruction, preoperative bloody/tarry stool, and anesthesia time at least 180 min were independent risk factors for postoperative VTE. The CRC-VTE model was developed from these seven factors and had good VTE predictive performance ( C -statistic 0.72, 95% CI 0.68-0.76). CONCLUSIONS: This study provided a national perspective on the incidence and prevention of VTE after CRC surgery in China. The study offers guidance for VTE prevention in patients after CRC surgery. A practical CRC-VTE risk predictive model was proposed.

Laparoscopic versus open appendectomy for acute appendicitis: a metaanalysis.

BACKGROUND: Currently, laparoscopic appendectomy (LA) provides a safe and effective alternative to open appendectomy (OA), but its use remains controversial. This study aimed to evaluate the efficiency and safety of LA through a metaanalysis. METHODS: Randomized controlled trials (RCTs) comparing LA and OA published between January 1992 and February 2010 were included in this study. Strict literature appraisal and data extraction were carried out independently by two reviewers. A metaanalysis then was performed to evaluate operative time, hospital cost, postoperative complications, length of analgesia, bowel function recovery, day liquid diet began, hospital stay, and return to work and normal activity. RESULTS: The metaanalysis comprised 25 RCTs involving 4,694 patients (2,220 LA and 2,474 OA cases). No significant differences were found between the LA and OA groups in terms of age, gender, body mass index (BMI), or type of appendiceal inflammation. Compared with OA, LA showed advantages of fewer postoperative complications (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.55-0.98; p = 0.04), less pain (length of analgesia: weighted mean difference [WMD], -0.53; 95% CI, -0.91 to -0.15; p = 0.007), earlier start of liquid diet (WMD, -0.51; 95% CI, -0.75 to -0.28; p < 0.0001), shorter hospital stay (WMD, -0.68; 95% CI, -1.02 to -0.35; p < 0.0001), and earlier return to work (WMD, -3.09; 95% CI, -5.22 to -0.97; p = 0.004) and normal activity (WMD, -4.73; 95% CI, -6.54 to -2.92; p < 0.00001), but a comparable hospital cost (WMD of LA/OA ratio, 0.11; 95% CI, -0.18 to 0.40; p = 0.47) and a longer operative time (WMD, 10.71; 95% CI, 6.76-14.66; p < 0.00001). CONCLUSION: Despite the longer operative time, LA results in less postoperative pain, faster postoperative rehabilitation, a shorter hospital stay, and fewer postoperative complications than OA. Therefore, LA is worth recommending as an effective and safe procedure for acute appendicitis.

Laparoscopic versus open appendectomy: a prospective randomized comparison.

BACKGROUND: Whether laparoscopy offers a benefit over open surgery in the management of acute appendicitis or not remains a subject of controversy despite the publication of numerous randomized studies. This study aimed to compare laparoscopic appendectomy (LA) with open appendectomy (OA) and to ascertain its therapeutic benefit. METHODS: Adult patients older than 14 years presenting with signs and symptoms suggestive of acute appendicitis were randomized to undergo either LA or OA from January 2006 to December 2007. Comparisons were based on operating time, time until return to a general diet, time until return to normal activity and work, length of hospital stay, billed charges, and postoperative complications. RESULTS: The study enrolled 220 patients: 108 to undergo OA and 112 to undergo LA. The groups were similar in terms of clinicopathologic characteristics. The operating time seemed to be shorter for the OA patients than for the LA patients, but the difference was not significant (LA, 30 +/- 15.2 min vs. OA, 28.7 +/- 16.3 min; p > 0.05). The hospital stay of 4.1 +/- 1.5 days for the LA group and 7.2 +/- 1.7 days for the OA group, and the difference was statistically significant (p < 0.05). Laparoscopic appendectomy remained associated with a shorter time until return to a general diet (LA, 20.2 +/- 12.4 h vs. OA, 36.5 +/- 10 h; p < 0.05), to normal activity (LA, 9.1 +/- 4.2 days vs. OA, 13.7 +/- 5.8 days; p < 0.05), and to work (LA, 21.2 +/- 3.5 days vs. OA, 27.7 +/- 4.9 days; p < 0.05). The billed charges appeared to be higher for LA (LA, 5,720.3 +/- 115.7 yuan vs. OA, 5,310 +/- 575.4 yuan), but this difference failed to be clinically important or statistically significant (p > 0.05). Wound infections were more common after OA (n = 14) than after LA (n = 0) (p < 0.05). Intraabdominal abscesses occurred for two patients in the LA group and nine patients in the OA group (p < 0.05). Postoperative ileus occurred with frequencies of 0% in the LA group and 7.4% in the OA group (p < 0.05). The rate for overall complications was significantly lower in the LA group. CONCLUSION: Laparoscopic appendectomy is a useful tool in the treatment of acute appendicitis. Its advantages lie in its minimal invasiveness, its better cosmetic outcome, its lower rate of complications based on surgical expertise and state-of-the-art equipment. It can be recommended as an adoptable method for the routine patient with appendicitis.

Celecoxib increases retinoid sensitivity in human colon cancer cell lines.

Retinoid resistance has limited the clinical application of retinoids as differentiation-inducing and apoptosis-inducing drugs. This study was designed to investigate whether celecoxib, a selective COX-2 inhibitor, has effects on retinoid sensitivity in human colon cancer cell lines, and to determine the possible mechanism of said effects. Cell viability was measured using the MTT assay. Apoptosis was detected via Annexin-V/PI staining and the flow cytometry assay. PGE(2) production was measured with the ELISA assay. The expression of RARbeta was assayed via western blotting. The results showed that celecoxib enhanced the inhibitory effect of ATRA in both COX-2 high-expressing HT-29 and COX-2 low-expressing SW480 cell lines. Further study showed the ATRA and celecoxib combination induced greater apoptosis, but that the addition of PGE(2) did not affect the enhanced growth-inhibitory and apoptosis-inducing effects of the combination. Moreover, NS398 (another selective COX-2 inhibitor) did not affect the inhibitory effects of ATRA in the two cell lines. Western blotting showed that the expression of RARbeta in HT-29 cell lines was increased by celecoxib, but not by NS398, and that the addition of PGE(2) did not affect the celecoxib-induced expression of the retinoic acid receptor beta. In conclusion, celecoxib increased the expression of RARbeta and the level of cellular ATRA sensitivity through COX-2-independent mechanisms. This finding may provide a potential strategy for combination therapy.

Laparoscopy-assisted D2 radical distal gastrectomy for advanced gastric cancer.

BACKGROUND/AIM: Laparoscopy-assisted surgery has proved useful in the treatment of early gastric cancer, but its use in advanced cancer has rarely been studied. To investigate the efficacy and advantages of laparoscopy-assisted distal gastrectomy (LADG) with D2 dissection of lymph nodes versus conventional open D2 distal gastrectomy (ODG) in advanced gastric cancer. METHODS: From January 2007 to June 2008, the clinical data of 66 cases of LADG for advanced gastric cancer were compared with that of 69 patients who, during the same period, underwent a conventional open radical distal gastrectomy. RESULTS: No patient in the LADG group converted to conventional operation with laparotomy. Operative time was significantly longer for the LADG group than for the ODG group (266.05 +/- 55.05 vs. 223.78 +/- 26.79 min). No significant differences were found in the total number of retrieved lymph nodes (25.81 +/- 12.53 vs. 27.47 +/- 10.28) between the two groups. Patients in the LADG group had less blood loss, shorter time of analgesic use, earlier recovery of bowel activity, and shorter postoperative hospitalization time. Complication rates were comparable between the two groups. CONCLUSIONS: LADG with D2 lymph node dissection is a safe and feasible procedure with adequate lymphadenectomy for the treatment of advanced gastric cancer. A large-scale prospective randomized trial with a longer follow-up period is needed to definitively assess whether LADG is a better alternative than ODG with D2 lymph node dissection.

[Expression and its significance of retinoic acid receptor-beta in colorectal cancer].

OBJECTIVE: To investigate the expression and its significance of retinoic acid receptor-beta (RAR-beta) in colorectal cancer. METHODS: RAR-beta was detected by immunohistochemistry methods and carcino-embryonic antigen (CEA) was tested by chemiluminescence immunoassay methods in normal tissues, paracancerous tissues and colorectal cancer tissues of 60 patients with colorectal cancer treated from January 2006 to January 2007. Above-mentioned data, together with the clinicopathological data of these 60 patients, were analyzed to figure out the expression and its significance of RAR-beta in colorectal cancer. RESULTS: The expression rate of RAR-beta in tumor tissues (48%) was significantly lower than those in both normal tissues (87%) and paracancerous tissues (87%) (P < 0.05). And its expression was also significant lower in patients with lymph node metastasis (32%) and patients with advanced cancer (TNM stage III and IV) (29%) than in those without lymph nodes metastasis (60%) and those with early stage cancer (stage I and II) (69%). There was no significant differences among well, mildly and poorly differentiated cancer tissues. The CEA level rose in 20 patients, and its rising rate was remarkably higher in patients with lymph node metastasis (48%) and in patients with advanced cancer (52%) than those without lymph node metastasis (23%) and in early stage(14%). CONCLUSIONS: The expression of RAR-beta decreases significantly in cancer tissues in patients with colorectal cancer, which may be related to the carcinogenesis of colorectal cancer; and its decreasing degree is correlated negatively with the lymph node metastasis and advanced clinicopathological stage. The expression level of RAR-beta may be a new prognostic indication of patients with colorectal cancer.

[Celecoxib increased cellular ATRA sensitivity of human colon cancer cell lines through COX-2-independent mechanisms].

Retinoid resistance has limited clinical activity of retinoids as differentiation-inducing and apoptosis-inducing drugs. The present study was designed to investigate whether celecoxib (selective COX-2 inhibitor) has effects on cellular retinoid sensitivity of human colon cancer cell lines and its possible mechanism. Cell viability was measured by MTT assay. Apoptosis was detected by Annexin-V/PI staining and flow cytometry assay. PGE2 production was measured by ELISA assay. Expression of RARbeta was assayed by Western blotting. The results showed that celecoxib enhanced the inhibitory effect of ATRA in both COX-2 high-expressing HT-29 and COX-2 low-expressing SW480 cell lines. Further study showed the ATRA and celecoxib combination induced greater apoptosis, and the addition of PGE2 did not affect the number of apoptotic cells induced by the combination. Moreover, NS398 (another selective COX-2 inhibitor) did not affect the inhibitory effects of ATRA on both cell lines. Western blotting showed that the expression of RARbeta in HT-29 cell lines increased in celecoxib group and combination group. And the addition of PGE2 did not affect the expression of RARbeta induced by celecoxib either. In conclusion, celecoxib increased expression of RARbeta and cellular ATRA sensitivity through COX-2-independent mechanisms, which may provide a potential strategy for combination therapy.

[Urinary function after pelvic autonomic nerve preservation of laparoscopic radical resection for rectal cancer].

OBJECTIVE: To evaluate the protection of urinary function after laparoscopic radical resection with pelvic autonomic nerve preservation (PANP) for rectal cancer. METHODS: Prospectively 139 patients with middle or low rectal cancer receiving surgery during November 2005 to October 2007 were divided into two groups (L-PANP, n = 63; O-PANP, n = 76). The radicalism and safety of L-PANP surgery were analyzed and the effects upon urinary function between the two groups assessed by follow-ups and urodynamic study. RESULTS: Patients receiving subtypes I and II of L-PANP surgery had less decrease in contraction of bladder than those receiving the same subtype of O-PANP surgery at 10 days post-operation (Z = -2.358, P = 0.018; Z = -2.268, P = 0.033). And no difference was observed in patients receiving subtype III PANP surgery (Z = -1.302, P = 0.237). However, no matter which subtype of PANP surgery, patients of L-PANP group had a better contraction of bladder than those of O-PANP group at 1 month post-operation (P < 0.05). The 1-year survival rate was 98.0% (50/51) in L-PANP group and 96.6% (57/59) in O-PANP group. And no statistical difference was found between them (P = 0.898). Meanwhile, the 1-year relapse rate of pelvic cavity was 3.9% (2/52) in L-PANP group and 5.1% (3/59) in O-PANP group. And no statistical difference was found between them (P = 0.867). CONCLUSION: As compared with O-PANP surgery, L-PANP surgery shows a superiority in protection of urinary function.

The implication of tumor-infiltrating lymphocytes in Epstein-Barr virus-associated gastric carcinoma.

Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a distinct entity that has conspicuously inflammatory infiltration compared with EBV-negative gastric carcinoma. To date, the local immune status in EBVaGC and its relationship with patient prognosis and apoptosis of tumor cells are largely unknown. In this study, we evaluated the density of different types of tumor-infiltrating lymphocytes (TILs) in 53 EBVaGCs and 67 EBV-negative gastric carcinomas and analyzed its relationship with patient outcomes and apoptosis of tumor cells in EBVaGC. The average number of CD3+ total T cells, CD8+ T cells, CD79α+ B cells, CD56+ natural killer cells, Fascin+ dendritic cells (DCs), and FoxP3+ Tregs and the average proportions of Ki-67, interleukin 1ß, granzyme B, interferon γ, and interleukin 10 in TILs were higher in EBVaGC, and CD8+ T cells were the predominant constituent cells of TILs in EBVaGC. Patients with higher numbers of CD3+ total T cells, CD8+ T cells, CD79α+ B cells, and Fascin+ DCs survived longer in EBVaGC, and CD8+ T cells and Fascin+ DCs were independent prognostic factors for patient survival. Besides, CD8+ T cells were positively correlated with apoptotic index of tumor cells. However, the apoptosis of tumor cells was lower, and the expression of survivin and NF-κBp65 in tumor cells was up-regulated in EBVaGC. These findings suggested that CD3+ total T cells, CD8+ T cells, CD79α+ B cells, and Fascin+ DCs predict a better prognosis in EBVaGC; CD8+ T cells might through a nonapoptotic pathway eliminate tumor cells, thereby improving the patient prognosis.

Effect of all-trans retinoic acid on drug sensitivity and expression of survivin in LoVo cells.

BACKGROUND: All-trans retinoic acid (ATRA) can influence the tumor cell proliferation cycle, and some chemotherapeutic drugs are cycle specific. In this study, we hypothesize that ATRA can enhance chemotherapeutic drug sensitivity by affecting the cell cycle of tumor cells. METHODS: The cell cycle of LoVo cells was evaluated using flow cytometry (FCM). Cell viability was analyzed using the MTT assay. The morphologic changes in the treated LoVo cells were measured with acridine orange (AO)/ethidium bromide (EB) staining. Expression of survivin in LoVo cells was analyzed by immunofluorescence assay. RESULTS: After LoVo cells were treated with ATRA, the G0/G1 ratio of the tumor cells increased and the cell ratio of S- and G2/M-phase decreased. Viability of the cells decreased significantly after combined treatment with ATRA and 5-fluorouracil (5-FU) or mitomycin c (MMC) and was evaluated by fluorescence microscopy. Expression level of survivin in the tumor cells decreased after ATRA combination treatment. CONCLUSIONS: ATRA enhances drug sensitivity of the LoVo cell line to cell cycle-specific agents and inhibits the expression of survivin in LoVo cells. The combination of ATRA and 5-FU or MMC promoted cell apoptosis, and the mechanism involved in apoptosis may be related to inhibition of survivin gene expression.

Analysis of the inhibitory effect of gypenoside on Na(+), K (+)-ATPase in rats' heart and brain and its kinetics.

OBJECTIVE: To study the effects of gypenoside (Gyp) on the activity of microsomal Na(+), K(+)-ATPase in rat's heart and brain in vitro. METHODS: The microsomal Na(+), K(+)-ATPase was prepared from rat's heart and brain by differential centrifugation. The activity of microsomal Na(+), K(+)-ATPase was assayed by colorimetric technique. Enzyme kinetic analysis method was used to analyze the effect of Gyp on the microsomal Na(+), K(+)-ATPase of rats. RESULTS: Gyp reversibly inhibited the brain and heart's microsomal Na(+), K(+)-ATPase in a concentration-dependent manner, and showed a more potent effect on enzyme in the brain. The IC(50) of Gyp for the heart and brain were 58.79+/-8.05 mg/L and 52.07+/-6.25 mg/L, respectively. The inhibition was enhanced by lowering the Na(+), or K(+) concentrations or increasing the ATP concentration. Enzyme kinetic studies indicated that the inhibitory effect of Gyp on the enzyme is like that of competitive antagonist of Na(+), the counter-competitive inhibitor for the substrate ATP, and the mixed-type inhibitor for K(+). CONCLUSION: Gyp displays its cardiotonic and central inhibitory effects by way of inhibiting heart and brain's microsomal Na(+), K(+)-ATPase activities in rats.

BRM promoter insertion polymorphisms increase the risk of cancer: A meta-analysis.

INTRODUCTION: Many studies have suggested that the BRM promoter insertion polymorphisms might be associated with susceptibility to many different types of cancer. However, previous studies reported contradictory results. This current meta-analysis was performed to address this issue. EVIDENCE ACQUISITION: A comprehensive search was conducted in multiple databases, including PubMed, Embase and China National Knowledge Infrastructure (CNKI). We collected relevant articles to explore the association between the BRM insertion polymorphisms and susceptibility of cancers. EVIDENCE SYNTHESIS: For the BRM-741 polymorphism, a total of 2901 cases and 3667 controls from 6 studies were included. For the BRM-1321 polymorphism, a total of 2899 cases and 3769 controls from 6 studies were included. Overall, a significant difference was observed in BRM-741 (OR 0.81; 95%CI 0.68, 0.96; P=0.02) and BRM-1321 (OR 0.76; 95%CI 0.66, 0.88; P<0.01) for allele frequency (D versus I). In the subgroup analysis, for the BRM-741, a significant difference was observed in Asian (OR 0.88; 95%CI 0.78, 0.99; P=0.03) for D versus I. Similarly, for the BRM-1321, a significant difference was observed in Asian (OR 0.43; 95%CI 0.32, 0.58; P<0.001) and Caucasian (OR 0.74; 95%CI 0.62, 0.88; P<0.001) for DD versus II. CONCLUSIONS: BRM-741 and BRM-1321 insertion polymorphisms are associated with susceptibility to cancer. Further studies are warranted to verify the clinical utility of BRM promoter insertion polymorphisms in human tumors.

Predictive models of adjuvant chemotherapy for patients with stage ii colorectal cancer: A retrospective study.

BACKGROUND: It remains controversial whether patients with Stage II colorectal cancer would benefit from adjuvant chemotherapy after radical resection. The aim of this study was to establish two mathematical models to identify the suitable patients for adjuvant chemotherapy. METHODS: The current study comprised of two steps. In the first step, 353 patients with Stage II colorectal cancer who underwent surgical procedures at the Third Affiliated Hospital of Sun Yat-sen University between June 2006 and December 2015 were entered and followed up for 6-120 months. Their clinical data were collected and enrolled into the database. We established two mathematical models by univariate and multivariate Cox regression analysis to identify the target patients; in the second step, 230 patients under the same standard between January 2012 and December 2016 were entered and followed up for 3-62 months to verify the two models' validation. RESULTS: In the first step, totally 340 surgical patients with Stage II colorectal cancer were finally enrolled in this study. Statistical analysis showed that tumor differentiation (TD) (P < 0.001), lymphovascular invasion (LVI) (P < 0.001), uncertain or positive margins (UPM) (P < 0.001), and fewer lymph nodes (LNs) (<12) retrieved (P < 0.001) were correlated with the overall survival (OS) and disease free survival (DFS). We obtained two models: (1) OS risk score = 1.116 × TD + 2.202 × LVI + 3.676 × UPM + 1.438 × LN - 0.493; (2) DFS risk score = 0.789 × TD + 2.074 × LVI + 3.183 × UPM + 1.329 × LN - 0.432. According to the models and cutoff points [(0.07, 1.33) and (-0.04, 1.30), respectively], patients can be divided into three groups: low-risk, moderate-risk, and high-risk. Moreover, the high-risk group patients could benefit from adjuvant chemotherapy. In the second step, totally 221 patients were finally used to verify the models' validation. The results proved that the models were accurate and feasible (P< 0.05). CONCLUSIONS: According to the predictive models, patients with Stage II colorectal cancer in the high-risk group are strongly recommended for adjuvant chemotherapy, thus facilitating the individualized and precise treatment.