Ki-67 Change in Anthracyline-containing Neoadjuvant Chemotherapy Response in Breast Cancer.

OBJECTIVE: Anthracycline-containing regimens are irreplaceable in neoadjuvant chemotherapy (NAC) for breast cancer (BC) at present. However, 30% of early breast cancer (EBC) patients are resistant to anthracycline-containing chemotherapy, leading to poor prognosis and higher mortality. Ki-67 is associated with the prognosis and response to therapy, and it changes after NAC. METHODS: A total of 105 BC patients who received anthracycline-containing NAC were enrolled. Then, the optimal model of Ki-67 was selected, and its predictive efficacy was analyzed. Immunohistochemistry (IHC) was used to determine the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) status and Ki-67 level. Fluorescent in situ hybridization (FISH) was used to verify the HER-2 when the IHC score was 2+. RESULTS: The post-NAC Ki67 level after treatment with anthracycline drugs was lower than pre-NAC Ki-67 (19.6%±23.3% vs. 45.6%±23.1%, P<0.001). Furthermore, patients with the Ki-67 decrease had a border line higher pathological complete response (pCR) rate (17.2% vs. 0.0%, P=0.068), and a higher overall response rate (ORR) (73.6% vs. 27.8%, P<0.001), when compared to patients without the Ki-67 decrease. The ΔKi-67 and ΔKi-67% were valuable markers for the prediction of both the pCR rate and ORR. The area under the curve (AUC) for ΔKi-67 on pCR and ORR was 0.809 (0.698-0.921) and 0.755 (0.655-0.855), respectively, while the AUC for ΔKi-67% on pCR and ORR was 0.857 (0.742-0.972) and 0.720 (0.618-0.822), respectively. Multivariate logistic regression model 1 revealed that ΔKi-67 was an independent predictor for both pCR [odds ratio (OR)=61.030, 95% confidence interval (CI)=4.709-790.965; P=0.002] and ORR (OR=10.001, 95% CI: 3.044-32.858; P<0.001). Multivariate logistic regression model 2 revealed that ΔKi-67% was also an independent predictor for both pCR (OR=408.922, 95% CI=8.908-18771.224; P=0.002) and ORR (OR=5.419, 95% CI=1.842-15.943; P=0.002). CONCLUSIONS: The present study results suggest that ΔKi67 and ΔKi67% are candidate predictors for anthracycline-containing NAC response, and that they may provide various information for further systematic therapy after surgery in clinical practice.

Endoplasmic Reticulum Protein 72 Regulates Integrin Mac-1 Activity to Influence Neutrophil Recruitment.

BACKGROUND: Integrins mediate the adhesion, crawling, and migration of neutrophils during vascular inflammation. Thiol exchange is important in the regulation of integrin functions. ERp72 (endoplasmic reticulum-resident protein 72) is a member of the thiol isomerase family responsible for the catalysis of disulfide rearrangement. However, the role of ERp72 in the regulation of Mac-1 (integrin αMß2) on neutrophils remains elusive. METHODS: Intravital microscopy of the cremaster microcirculation was performed to determine in vivo neutrophil movement. Static adhesion, flow chamber, and flow cytometry were used to evaluate in vitro integrin functions. Confocal fluorescent microscopy and coimmunoprecipitation were utilized to characterize the interactions between ERp72 and Mac-1 on neutrophil surface. Cell-impermeable probes and mass spectrometry were used to label reactive thiols and identify target disulfide bonds during redox exchange. Biomembrane force probe was performed to quantitatively measure the binding affinity of Mac-1. A murine model of acute lung injury induced by lipopolysaccharide was utilized to evaluate neutrophil-associated vasculopathy. RESULTS: ERp72-deficient neutrophils exhibited increased rolling but decreased adhesion/crawling on inflamed venules in vivo and defective static adhesion in vitro. The defect was due to defective activation of integrin Mac-1 but not LFA-1 (lymphocyte function-associated antigen-1) using blocking or epitope-specific antibodies. ERp72 interacted with Mac-1 in lipid rafts on neutrophil surface leading to the reduction of the C654-C711 disulfide bond in the αM subunit that is critical for Mac-1 activation. Recombinant ERp72, via its catalytic motifs, increased the binding affinity of Mac-1 with ICAM-1 (intercellular adhesion molecule-1) and rescued the defective adhesion of ERp72-deficient neutrophils both in vitro and in vivo. Deletion of ERp72 in the bone marrow inhibited neutrophil infiltration, ameliorated tissue damage, and increased survival during murine acute lung injury. CONCLUSIONS: Extracellular ERp72 regulates integrin Mac-1 activity by catalyzing disulfide rearrangement on the αM subunit and may be a novel target for the treatment of neutrophil-associated vasculopathy.

Colloidal crystals array enabled bionic biliary stent for efficient domestic biofluid management.

In vivo surgical interventions require effective management of biofluids, including controlling bleeding and removing excess biofluids such as bile, wound exudate, and blood. To address these issues, recent advances have emerged, such as self-sealing needles, drug-eluting stents, and shear-thinning hydrogels. However, complications associated with intestinal mucosal injury and secondary damage still persist. Therefore, a multifunctional stent is urgently required that can effectively remove excessive biofluid. Surface wettability of biliary stents is crucial in biofluid management, and conventional coatings can cause adhesion to wound tissue. To overcome this issue, we developed an interpenetrating Janus wettability stent coating, enabling unidirectional draining of excessive biofluid from its hydrophobic side to hydrophilic side, thereby preventing biofluid from wetting the wound. Furthermore, we demonstrate a directional biofluid movement using a self-pumping dressing in an infected tissue model, providing a new approach for in situ biofluid collection and disease diagnosis by detecting metal ion changes. Overall, our integrated system presents an opportunity to design wound dressings with effective biofluid management and metal ion detection capabilities.

Remimazolam besylate versus propofol for deep sedation in critically ill patients: a randomized pilot study.

OBJECTIVE: To compare the efficacy and safety of remimazolam besylate and propofol for deep sedation in critically ill patients. METHODS: In this single-center, prospective, randomized, controlled pilot study, patients in the intensive care unit (ICU) requiring deep sedation were randomized to receive remimazolam besylate or propofol intravenously. Deep sedation was defined as a Richmond Agitation and Sedation Scale (RASS) score of - 4 or - 5. Sedation depth was monitored using RASS and Narcotrend Index (NI). The primary outcome was the percentage of time within the target sedation range without rescue sedation. The secondary outcomes included ventilator-free hours within 7 days, successful extubation, length of ICU stay, and 28-day mortality. Adverse events during the interventional period were also recorded. RESULTS: Thirty patients were assigned to each group. The median (IQR) RASS score was - 5.0 (- 5.0, - 4.0), and the median (IQR) NI value was 29.0 (21.0, 37.0) during the intervention period. Target RASS was reached a median of 100% of the sedation time in the two groups. No significant differences were observed in ventilator-free hours within 7 days, successful extubation, length of ICU stay, or 28-day mortality among groups. Hypotension occurred in 16 (53.3%) patients of remimazolam group and 18 (60.0%) patients of propofol group (p > 0.05). No patient experienced bradycardia. CONCLUSIONS: Remimazolam besylate appears to be an effective and safe agent for short-term deep sedation in critically ill patients. Our findings warrant large sample-sized randomized clinical trials.

Long-term sedation with remimazolam besylate versus propofol in critically ill patients during invasive mechanical ventilation: a study protocol for a multicenter randomized non-inferior trial.

Background: Remimazolam besylate is a novel ultra-short-acting benzodiazepine that can potentially be a safe and effective sedative in intensive care units. This study aims to assess whether remimazolam besylate is not inferior to propofol in maintaining mild-to-moderate sedation in critically ill patients receiving long-term mechanical ventilation. Methods and analysis: This is a multicenter, randomized, single-blind, propofol-controlled, non-inferiority study. Eligible patients are randomly assigned to receive remimazolam besylate or propofol in a 1:1 ratio to maintain a Richmond Agitation-Sedation Scale score between -3 and 0. When patients are under-sedated, rescue sedation of dexmedetomidine is added. The primary outcome is the percentage of time in the target sedation range. The secondary outcomes are hours free from the invasive ventilator in 7 days, successful extubation in 7 days, and weaning time, the length of intensive care unit stay, the length of hospital stay, and mortality in 28 days. Modified intention-to-treat and safety analysis is performed. Clinical trial registration number: https://clinicaltrials.gov/ct2/show/NCT05555667.

Bacillus subtilis pretreatment alleviates ethanol-induced acute liver injury by regulating the Gut-liver axis in mice.

This study was designed to investigate the hepatoprotective effects of Bacillus subtilis, a commensal bacterial species in the human gut, on ethanol-induced acute liver damage and the underlying mechanisms in mice. Male ICR mice challenged with three doses of ethanol (5.5 g/kg BW) exhibited a significant increase in serum aminotransferase activities and TNF-α level, liver fat accumulation, and activation of NF-κB signaling and NLRP3 inflammasome, which was suppressed by pretreatment with Bacillus subtilis. Besides, Bacillus subtilis inhibited acute ethanol-induced intestinal villi shortening and epithelial loss, the decline of protein levels of intestinal tight junction protein ZO-1 and occludin, and elevation of serum LPS level. Furthermore, the upregulation of mucin-2 (MUC2) and the downregulation of anti-microbial Reg3B and Reg3G levels induced by ethanol were repressed by Bacillus subtilis. Lastly, Bacillus subtilis pretreatment significantly increased the abundance of the intestinal Bacillus, but had no effects on the binge drinking-induced increase of Prevotellaceae abundance. These results demonstrate that Bacillus subtilis supplementation could ameliorate binge drinking-induced liver injury, and thus may serve as a functional dietary supplement for binge drinkers.

Influenza A Virus (H1N1) Infection Induces Glycolysis to Facilitate Viral Replication.

Viruses depend on host cellular metabolism to provide the energy and biosynthetic building blocks required for their replication. In this study, we observed that influenza A virus (H1N1), a single-stranded, negative-sense RNA virus with an eight-segmented genome, enhanced glycolysis both in mouse lung tissues and in human lung epithelial (A549) cells. In detail, the expression of hexokinase 2 (HK2), the first enzyme in glycolysis, was upregulated in H1N1-infected A549 cells, and the expression of pyruvate kinase M2 (PKM2) and pyruvate dehydrogenase kinase 3 (PDK3) was upregulated in H1N1-infected mouse lung tissues. Pharmacologically inhibiting the glycolytic pathway or targeting hypoxia-inducible factor 1 (HIF-1), the central transcriptional factor critical for glycolysis, significantly reduced H1N1 replication, revealing a requirement for glycolysis during H1N1 infection. In addition, pharmacologically enhancing the glycolytic pathway further promoted H1N1 replication. Furthermore, the change of H1N1 replication upon glycolysis inhibition or enhancement was independent of interferon signaling. Taken together, these findings suggest that influenza A virus induces the glycolytic pathway and thus facilitates efficient viral replication. This study raises the possibility that metabolic inhibitors, such as those that target glycolysis, could be used to treat influenza A virus infection in the future.

Patients with Prolonged Positivity of SARS-CoV-2 RNA Benefit from Convalescent Plasma Therapy: A Retrospective Study.

Convalescent plasma therapy has been implemented in a few cases of severe coronavirus disease 2019. No report about convalescent plasma therapy in treating patients with prolonged positivity of SARS-CoV-2 RNA has been published. In this study, we conducted a retrospective observational study in 27 patients with prolonged positivity of SARS-CoV-2 RNA, the clinical benefit of convalescent plasma therapy were analyzed. qRT-PCR test of SARS-CoV-2 RNA turned negative (≤ 7 days) in a part of patients (early negative group, n = 15) after therapy, others (late negative group, n = 12) turned negative in more than 7 days. Pulmonary imaging improvement was confirmed in 7 patients in early negative group and 8 in late negative group after CP therapy. Viral load decreased in early negative group compared with late negative group at day 3, 5, 7 after implementing convalescent plasma therapy. Patients in early negative group had a shorter median length of hospital stay. In conclusion, convalescent plasma therapy might help eliminate virus and shorten length of hospital stay in patients with prolonged positivity of SARS-CoV-2 RNA.

HMGB1 aggravates lipopolysaccharide-induced acute lung injury through suppressing the activity and function of Tregs.

BACKGROUND: CD4+CD25+FoxP3+ T helper cells (Tregs), a subgroup of CD4+ T helper cells, are critical effectors that protect against acute lung injury (ALI) by contact-dependent suppression or releasing anti-inflammatory cytokines including interleukin-10 (IL-10), and transforming growth factor (TGF-ß). HMGB1 (High mobility group box 1 protein) was identified as a nuclear non-histone DNA-binding chromosomal protein, which participates in the regulation of lung inflammatory response and pathological processes in ALI. Previous studies have suggested that Tregs overexpresses the HMGB1-recognizing receptor. However, the interaction of HMGB1 with Tregs in ALI is still unclear. OBJECTIVE: To investigate whether HMGB1 aggravates ALI by suppressing immunosuppressive function of Tregs. METHODS: Anti-HMGB1 antibody and recombinant mouse HMGB1 (rHMGB1) were administered in lipopolysaccharide (LPS)-induced ALI mice and polarized LPS-primed Tregs in vitro. The Tregs pre-stimulated with or without rHMGB1 were adoptively transferred to ALI mice and depleted by Diphtheria toxin (DT). For coculture experiment, isolated Tregs were first pre-stimulated with or without rHMGB1 or anti-HMGB1 antibody, then they were cocultured with bone marrow-derived macrophages (BMMs) under LPS stimulation. RESULTS: Tregs protected against acute lung pathological injury. HMGB1 modulated the suppressive function of Tregs as follows: reduction in the number of the cells and the activity of Tregs, the secretion of anti-inflammatory cytokines (IL-10, TGF-ß) from Tregs, the production of IL-2 from CD4+ T cells and CD11c+ DCs, and the M2 polarization of macrophages, as well as inducing proinflammatory response of macrophages. CONCLUSIONS: HMGB1 could aggravate LPS induced-ALI through suppressing the activity and function of Tregs.

Clinical course and predictors of 60-day mortality in 239 critically ill patients with COVID-19: a multicenter retrospective study from Wuhan, China.

BACKGROUND: The global numbers of confirmed cases and deceased critically ill patients with COVID-19 are increasing. However, the clinical course, and the 60-day mortality and its predictors in critically ill patients have not been fully elucidated. The aim of this study is to identify the clinical course, and 60-day mortality and its predictors in critically ill patients with COVID-19. METHODS: Critically ill adult patients admitted to intensive care units (ICUs) from 3 hospitals in Wuhan, China, were included. Data on demographic information, preexisting comorbidities, laboratory findings at ICU admission, treatments, clinical outcomes, and results of SARS-CoV-2 RNA tests and of serum SARS-CoV-2 IgM were collected including the duration between symptom onset and negative conversion of SARS-CoV-2 RNA. RESULTS: Of 1748 patients with COVID-19, 239 (13.7%) critically ill patients were included. Complications included acute respiratory distress syndrome (ARDS) in 164 (68.6%) patients, coagulopathy in 150 (62.7%) patients, acute cardiac injury in 103 (43.1%) patients, and acute kidney injury (AKI) in 119 (49.8%) patients, which occurred 15.5 days, 17 days, 18.5 days, and 19 days after the symptom onset, respectively. The median duration of the negative conversion of SARS-CoV-2 RNA was 30 (range 6-81) days in 49 critically ill survivors that were identified. A total of 147 (61.5%) patients deceased by 60 days after ICU admission. The median duration between ICU admission and decease was 12 (range 3-36). Cox proportional-hazards regression analysis revealed that age older than 65 years, thrombocytopenia at ICU admission, ARDS, and AKI independently predicted the 60-day mortality. CONCLUSIONS: Severe complications are common and the 60-day mortality of critically ill patients with COVID-19 is considerably high. The duration of the negative conversion of SARS-CoV-2 RNA and its association with the severity of critically ill patients with COVID-19 should be seriously considered and further studied.

An infectious clone of enterovirus 71(EV71) that is capable of infecting neonatal immune competent mice without adaptive mutations.

Enterovirus 71 (EV71) is a major pathogen that causes hand, foot and mouth disease (HFMD), which is a life threatening disease in certain children. The pathogenesis of EV71-caused HFMD is poorly defined due to the lack of simple and robust animal models with severe phenotypes that recapitulate symptoms observed in humans. Here, we generated the infectious clone of a clinical isolate from a severe HFMD patient. Virus rescued from the cDNA clone was infectious in cell lines. When administrated intraperitoneally to neonatal ICR, BALB/c and C57 immune competent mice at a dosage of1.4 × 104 pfu per mouse, the virus caused weight loss, paralysis and death in the infected mice after 4-5 days of infection. In the infected mice, detectable viral replication was detected in various tissues such as heart, liver, brain, lung, kidney, small intestine, leg skeletal muscle and medulla oblongata. The histology of the infected mice included massive myolysis, glomerular atrophy, villous blunting in small intestine, widened alveolar septum, diminished alveolar spaces and lymphocytes infiltration into the lung. By using the UV-inactivated virus as a control, we elucidated that the virus first amplified in the leg skeletal muscle tissue and the muscle tissue served as a primary viral replication site. In summary, we generated a stable EV71 infectious clone that is capable of infecting neonatal immune competent mice without adaptive mutations and provide a simple, valuable animal model for the studies of EV71pathogenesis and therapy.

Astragaloside IV attenuates IL-1ß secretion by enhancing autophagy in H1N1 infection.

Excessive secretion of inflammatory factors (cytokine storm) plays a significant role in H1N1-induced acute pneumonia, and autophagy acts as a cell-intrinsic mechanism to regulate inflammation. Astragaloside IV (AS-IV), originating from the astragalus root, possesses multiple pharmacological activities, such as anti-inflammation. However, the influences of AS-IV on H1N1-induced autophagy and inflammation have remained elusive. It has been reported that H1N1 infection leads to the accumulation of autophagosomes but obstructs autophagosomes incorporating into lysosomes, whereas the present study showed that AS-IV enhanced autophagy activation in H1N1 infection. Furthermore, we found that AS-IV promoted H1N1-triggered formation of autophagosomes and autolysosomes. Additionally, it was noted that AS-IV did not affect viral replication, mRNA level of interleukin-1 beta (IL-1ß) and pro-IL-1ß protein level, but significantly decreased secretion of IL-1ß, and chloroquine (CQ, as an inhibitor of autophagy) increased secretion of IL-1ß in H1N1 infection. In conclusion, AS-IV stimulates the formation of autophagosomes and the fusion of autophagosomes and lysosomes in H1N1 infection and may lead to decreased IL-1ß secretion.

A Novel Risk-Stratification Models of the High-Flow Nasal Cannula Therapy in COVID-19 Patients With Hypoxemic Respiratory Failure.

Background: High-flow nasal cannula (HFNC) has been recommended as a suitable choice for the management of coronavirus disease 2019 (COVID-19) patients with acute hypoxemic respiratory failure before mechanical ventilation (MV); however, delaying MV with HFNC therapy is still a dilemma between the technique and clinical management during the ongoing pandemic. Methods: Retrospective analysis of COVID-19 patients treated with HFNC therapy from four hospitals of Wuhan, China. Demographic information and clinical variables before, at, and shortly after HFNC initiation were collected and analyzed. A risk-stratification model of HFNC failure (the need for MV) was developed with the 324 patients of Jin Yin-tan Hospital and validated its accuracy with 69 patients of other hospitals. Results: Among the training cohort, the median duration of HFNC therapy was 6 (range, 3-11), and 147 experienced HFNC failure within 7 days of HFNC initiation. Early predictors of HFNC failure on the basis of a multivariate regression analysis included age older than 60 years [odds ratio (OR), 1.93; 95% confidence interval (CI), 1.08-3.44; p = 0.027; 2 points], respiratory rate-oxygenation index (ROX) <5.31 (OR, 5.22; 95% CI, 2.96-9.20; p < 0.001; 5 points) within the first 4 h of HFNC initiation, platelets < 125 × 109/L (OR, 3.04; 95% CI, 1.46-6.35; p = 0.003; 3 points), and interleukin 6 (IL-6) >7.0 pg/mL (OR, 3.34; 95% CI, 1.79-6.23; p < 0.001; 3 points) at HFNC initiation. A weighted risk-stratification model of these predictors showed sensitivity of 80.3%, specificity of 71.2% and a better predictive ability than ROX index alone [area under the curve (AUC) = 0.807 vs. 0.779, p < 0.001]. Six points were used as a cutoff value for the risk of HFNC failure stratification. The HFNC success probability of patients in low-risk group (84.2%) was 9.84 times that in the high-risk group (34.8%). In the subsequent validation cohort, the AUC of the model was 0.815 (0.71-0.92). Conclusions: Aged patients with lower ROX index, thrombocytopenia, and elevated IL-6 values are at increased risk of HFNC failure. The risk-stratification models accurately predicted the HFNC failure and early stratified COVID-19 patients with HFNC therapy into relevant risk categories.

Serum Inflammatory Cytokines Comparison in Gastric Cancer Therapy.

To compare serum inflammatory cytokines between laparoscopic-assisted and open radical gastrectomy in the perioperative period, 80 cases of advanced gastric cancer were chosen for the study. They were divided into laparoscopy group (40 cases) and abdominal open surgery group (40 cases), performed laparoscopic-assisted radical gastrostomy and conventional open radical gastrectomy, respectively. Serum Heme oxygenase-1 (HO-1), TNF-α, IL-6 and CRP were measured by ELISA on preoperative day 1, post-operative day 1 and post-operative day3. Serum HO-1, TNF-α, IL-6 and CRP had no significant difference between the laparoscopy group and the open group on pre-operative day 1. Serum HO-1, IL-6 and CRP of the laparoscopy group were significantly lower than that of the open group on post-operative day 1 and day 3 except for Serum TNF-α which had no significant difference. Laparoscopic-assisted radical gastrectomy was minimally invasive compared with conventional open radical gastrectomy in advanced gastric cancer patients.

circHIPK3 regulates lung fibroblast-to-myofibroblast transition by functioning as a competing endogenous RNA.

Myofibroblasts predominantly emerging through fibroblast-to-myofibroblast transition (FMT) are considered to be the key collagen-producing cells in pulmonary fibrosis. Circular RNAs (circRNAs) are important players involved in many biological processes. circHIPK3 has been identified as the one of the most abundant circRNAs in human lung. In this study, we characterized the role of circHIPK3 in pulmonary fibrosis. We revealed that circHIPK3 is upregulated in bleomycin-induced pulmonary fibrosis mice model, FMT-derived myofibroblasts. circHIPK3 silencing can ameliorate FMT and suppress fibroblast proliferation in vivo and vitro. Fundamentally, circHIPK3 regulates FMT by functioning as an endogenous miR-338-3p sponge and inhibit miR-338-3p activity, thereby leading to increased SOX4 and COL1A1 expression. Moreover, dysregulated circHIPK3 expression was detected in the clinical samples of patients with idiopathic pulmonary fibrosis. Intervention of circHIPK3 may represent a promising therapy for pulmonary fibrosis.

Influenza A virus (H1N1) triggers a hypoxic response by stabilizing hypoxia-inducible factor-1α via inhibition of proteasome.

Virus reprogramming of host cellular function is a critical strategy for viral survival and replication. A better understanding of virus-host interaction may provide new potential avenues for the treatment of viral diseases. It has been reported that hypoxia-inducible factor-1 (HIF-1) pathway is activated by a range of pathogens via different mechanisms, but the impact of Influenza A virus on HIF-1 signaling is still unclear. In this study, we observed H1N1 infection stabilized HIF-1α under normoxic conditions. In detail, H1N1 did not increase HIF-1α mRNA transcription, nor impaired posttranslational prolyl hydroxylation or ubiquitination of HIF-1α, but inhibited the function of proteasome, resulting in HIF-1α accumulation. Furthermore, a decreased expression of factor inhibiting HIF-1 (FIH-1), which hydroxylates asparagine 803 within HIF-1α to repress HIF-1α activity, was seen after H1N1 infection. Taken together, these findings reveal a previously unrecognized mechanism of viral activation of the HIF-1 pathway, resembling a hypoxic response in normoxia.

Comparison Between Laparoscopic and Open Resection Following Neoadjuvant Chemoradiotherapy for Mid-Low Rectal Cancer Patients: A Meta-Analysis.

INTRODUCTION: The optimal approach of resection for mid-low rectal cancer after neoadjuvant chemoradiotherapy (nCRT) is still controversial. The aim of this meta-analysis was to clarify the safety and feasibility of laparoscopic surgery compared with open resection. MATERIALS AND METHODS: We performed a literature search for studies on PubMed, Embase and Cochrane Library up to March 1, 2018. Review Manager software was applied for data analysis. We used weighted mean difference (WMD) for continuous parameters and odds ratio (OR) for dichotomous variables. Confidence interval (CI) was set at 95% and a P value <.05 was considered statistically significant. RESULTS: A total of seven studies met the inclusion criteria for the meta-analysis: 466 patients in laparoscopic group and 491 in open group. The pooled result revealed that laparoscopic resection had a favorable blood loss (WMD = -116.88 mL; 95% CI: -189.78 to -43.99; P = .002), analogous lymph nodes harvest (WMD = -0.30; 95% CI: -1.29 to 0.70; P = .56), less postoperative complications (OR = 0.63; 95% CI: 0.46-0.88; P = .006), shorter time to pass first flatus (WMD = -0.76 day; 95% CI: -1.00 to -0.51; P < .00001), and stay in hospital (WMD = -2.71 days; 95% CI: -4.54 to -0.88; P = .004), despite similar operating time (WMD = 11.17 minutes; 95% CI: -14.37 to 36.70; P = .39). CONCLUSIONS: Laparoscopic resection might be a technically safe and feasible approach for mid-low rectal cancer patients after nCRT compared with open resection.

MMP9 is involved in HO-1-mediated upregulation of apical junctional complex in Caco-2 cells under oxygen-glucose deprivation.

Ischemia reperfusion injury is a critical factor in the recovery process after intestine trauma and the functional restoration of intestinal reconstruction. This study was the first to explore the expression of apical junctional complex (AJC) induced by heme oxygenase-1 (HO-1) in Caco-2 cells in oxygen-glucose deprivation (OGD) models. Here we showed that HO-1 was upregulated after OGD. Notably, activation of HO-1 largely enhanced the expression of AJC proteins including Claudin-4, E-cadherin and ß-catenin in Caco-2 cells, but decreased the expression of matrix metalloproteinase 9 (MMP9). Knockdown of HO-1 attenuated the OGD-induced overexpression of AJC proteins but promoted the expression of MMP9. Interestingly, inhibition of MMP9 further enhanced AJC expression. These results suggest that HO-1 is involved in OGD-evoked upregulation of AJC proteins, which is partly mediated by MMP9 pathway. High expression of HO-1 may play an important role in the pathophysiological process of ischemia reperfusion injury and has potential clinical value for the treatment of intestine related diseases.