Different antithrombotic strategies after coronary artery bypass grafting to prevent adverse events: a retrospective analysis.

OBJECTIVE: Coronary artery bypass grafting (CABG) is associated with antithrombotic therapy in terms of postoperative adverse events; however, it is still unknown whether the early use of such drugs after CABG is safe and effective. In this study, we aim to evaluate the relationship between different postoperative antithrombotic strategies and in-hospital adverse events in patients undergoing isolated coronary artery bypass grafting surgery. METHODS: This was a single-center, retrospective cohort analysis of patients undergoing isolated CABG due to coronary artery disease (CAD) between 2001 and 2012. Data were extracted from the Medical Information Mart for Intensive Care III database. The patients involved were divided into the ASA (aspirin 81 mg per day only) or DAPT (aspirin plus clopidogrel 75 mg per day) group according to the antiplatelet strategy. Patients were also stratified into subgroups based on the type of anticoagulation. The in-hospital risk of bleeding and adverse events was investigated and compared between groups. Propensity score matching (PSM) was performed to reduce the potential effects of a selection bias. RESULTS: A total of 3274 patients were included in this study, with 2358 in the ASA group and 889 in the DAPT group. Following the PSM, no significant difference was seen in the risk of major bleeding between the two groups according to the PLATO, TIMI or GUSTO criteria. There was no difference in the postoperative mortality. In subgroup analysis, patients given anticoagulant therapy had an increased incidence of bleeding-related events. Multivariable analysis revealed that postoperative anticoagulant therapy and the early use of heparin, but not DAPT, were independent predictors of bleeding-related events. CONCLUSIONS: Postoperative DAPT was not associated with an increased occurrence of bleeding-related events in patients undergoing isolated CABG and appears to be a safe antiplatelet therapy. The addition of anticoagulants to antiplatelet therapy increased the risk of bleeding and should be considered cautiously in clinical practice.

Sirtuin1 (sirt1) regulates the glycolysis pathway and decreases cisplatin chemotherapeutic sensitivity to esophageal squamous cell carcinoma.

We aimed to evaluate the influence of sirtuin1 (sirt1) on the ESCC chemotherapeutic sensitivity to cisplatin. We used ESCC cell ablation sirt1 for establishing a xenograft mouse tumor model. The tumor volume was then detected. sirt1 was over-expressed significantly in ESCC patients and cells. Moreover, sirt1 knockdown raised ESCC sensitivity to cisplatin. Besides, glycolysis was associated with ESCC cell chemotherapy resistance to cisplatin. Furthermore, sirt1 increased ESCC cells' cisplatin chemosensitivity through HK2. Sirt1 enhanced in vivo ESCC chemosensitivity to cisplatin. Overall, these findings suggested that sirt1 knockdown regulated the glycolysis pathway and raised the ESCC chemotherapeutic sensitivity.

Gas therapy strategies for depression and schizophrenia: A review.

Depression and schizophrenia are 2 serious mental disorders. Their effective treatment is an urgent medical and social problem at present. Drug treatment is the basic measure to improve mental disorders, especially serious mental disorders. However, the side effects of traditional antipsychotic drugs cannot be avoided. Surprisingly, in recent years, it has been found that nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S) and hydrogen (H2) can regulate corresponding signal pathways to treat mental diseases in animal models. More importantly, as gas signal molecules, they will not bring toxicity and side effects after metabolism. Therefore, in this review, we analyzed the effects of gas on depression and schizophrenia through endogenous gas generation and external gas delivery strategies in some animal models. Endogenous gas generation strategy: summarized the therapeutic mechanism of gas signaling molecules on depression and schizophrenia, and listed the main ways to inhibit or stimulate gas generation. External gas delivery strategy: The common external stimuli-responsive gasotransmitter prodrugs and some study of these prodrugs in the treatment of depression and schizophrenia are summarized. We also analyzed the prospects of nano-gas carrier in the treatment of depression and schizophrenia. Through this review, we hope to provide guidance for treating depression and schizophrenia by regulating relevant gas signal pathways, and provide reference for developing safe and effective drugs for treating mental disorders by summarizing exogenous gas drugs.

[Effect of 28-day administration of Psoraleae Fructus water extract on early liver injury in rats].

This study aims to investigate the hepatotoxicity of Psoraleae Fructus water extract and the underlying mechanism in rats. Forty-eight rats were randomly assigned into four groups: a blank group and low-(BZGL, 6.25 g·kg~(-1)), medium-(BGZM, 12.5 g·kg~(-1)), and high-dose(BGZH, 25 g·kg~(-1)) Psoraleae Fructus water extract groups. The rats were treated for 28 days, and toxicity and mortality were observed daily. After 28 days, the rats were sacrificed, and the body weight, liver index, and liver-to-brain ratio were calculated. The morphological changes in the liver tissue were observed, and the serum levels of related biochemical indicators were measured. The results showed that compared with the blank group, Psoraleae Fructus water extracts of different doses decreased the body weight, increased the liver index and liver-to-brain ratio, and caused liver hypertrophy and pathological changes. Pathological examination revealed that the rats in Psoraleae Fructus water extract groups had bile duct hyperplasia, inflammatory cell infiltration, and liver cell fibrosis. Compared with the blank group, BGZL elevated the levels of alanine transaminase(ALT), α-glutathione S-transferase(α-GST), and total bile acid(TBA)(P<0.05), and BGZM and BGZH elevated the levels of ALT, TBA, α-GST, γ-glutamyl transferase(γ-GT), purine nucleoside phosphorylase(PNP), ornithine carbamoyltransferase(OCT), and arginase(ArgI)(P<0.05). Compared with the blank group, Psoraleae Fructus water extracts of different doses down-regulated the mRNA and protein levels of bile salt export pump(BSEP) and farnesoid X receptor(FXR) and up-regulated the mRNA and protein levels of tumor necrosis factor-α(TNF-α), nuclear factor kappaB(NF-κB), and cholesterol 7 alpha-hydroxylase(CYP7A1)(P<0.05). The results suggested that Psoraleae Fructus water extract caused toxicity in rats, showing a dose-toxicity relationship. Psoraleae Fructus water extract may cause liver damage, which may be due to its effect on liver bile acid secretion and induction of inflammation.

Analysis of the expression and prognostic significance of DDK complex in Hepatocarcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) remains one of the most common and lethal malignancies worldwide. Although DBF4-dependent kinase (DDK) complex composed of CDC7 kinase and its regulatory subunit DBF4 has been shown to be overexpressed in primary tumors and promotes tumor development, while its role and prognostic value in HCC remain largely unknown. In the present study, the expression of DBF4 and CDC7 and their relationship with clinical characteristics were comprehensively analyzed. METHODS: The mRNA expression profiles of HCC and the corresponding clinical data of HCC patients were downloaded from TCGA and GEO databases, respectively. The differences in DBF4 and CDC7 expression in tumor tissues and adjacent normal tissues were analyzed. HCC-derived tissue microarray (TMA) was used to evaluate and score the expression of CDC7 by immunohistochemistry (IHC) staining. The Kaplan-Meier method and the Cox regression method were used to analyze the relationship between overall survival and clinical characteristics of the patients. Gene set enrichment analysis (GSEA) was used to analyze the pathway enrichment of DBF4 and CDC7. RESULTS: DBF4 and CDC7 had similar expression patterns in HCC patients. Detailly, compared with adjacent tissues, both mRNA and protein of DBF4 and CDC7 were significantly higher in HCC, and their expression was positively correlated with AJCC_T stage, clinical stage and G stage (grade) of liver cancer patients, and higher DBF4 or CDC7 expression predicted a worse prognosis in HCC patients with shorter overall survival (OS), recurrence-free survival (RFS), disease-specific survival (DSS) and progress-free survival (PFS). Cox regression analysis suggested that both DBF4 and CDC7 were independent risk factors for the prognosis of HCC patients in TCGA dataset. GSEA suggested that both DBF4 and CDC7 were positively correlated with cell cycle and DNA replication. Finally, the prognostic value of CDC7 was furtherly confirmed by TMA-based IHC staining results. CONCLUSIONS: Our study showed that DDK complex was significantly increased in HCC. Both DBF4 and CDC7 may be potential diagnostic and prognostic markers for HCC, and high expression of DDK members predicts a worse prognosis in patients with HCC, which may be associated with high tumor cell proliferation rate.

PNA-Modified Liposomes Improve the Delivery Efficacy of CAPIRI for the Synergistic Treatment of Colorectal Cancer.

Tumor-associated antigen mucin 1 (MUC1) is highly expressed in colorectal cancer and is positively correlated with advanced stage at diagnosis and poor patient outcomes. The combination of irinotecan and capecitabine is standard chemotherapy for metastatic colorectal cancer and is known as XELIRI or CAPIRI, which significantly prolongs the progression-free survival and overall survival of colorectal cancer patients compared to a single drug alone. We previously reported that peanut agglutinin (PNA)-conjugated liposomes showed enhanced drug delivery efficiency to MUC1-positive liver cancer cells. In this study, we prepared irinotecan hydrochloride (IRI) and capecitabine (CAP)-coloaded liposomes modified by peanut agglutinin (IRI/CAP-PNA-Lips) to target MUC1-positive colorectal cancer. The results showed that IRI/CAP-PNA-Lips showed an enhanced ability to target MUC1-positive colorectal cancer cells compared to unmodified liposomes. Treatment with IRI/CAP-PNA-Lips also increased the proportion of apoptotic cells and inhibited the proliferation of colorectal cancer cells. The targeting specificity for tumor cells and the antitumor effects of PNA-modified liposomes were significantly increased in tumor-bearing mice with no severe cytotoxicity to normal tissues. These results suggest that PNA-modified liposomes could provide a new delivery strategy for the synergistic treatment of colorectal cancer with clinical chemotherapeutic agents.

GA&HA-Modified Liposomes for Co-Delivery of Aprepitant and Curcumin to Inhibit Drug-Resistance and Metastasis of Hepatocellular Carcinoma.

Background: Tumor microenvironment (TME) plays a vital role in the development of hepatocellular carcinoma (HCC). Mounting evidence indicates that peripheral nerves could induce a shift from quiescent hepatic stellate cells (HSCs) to cancer-associated fibroblasts (CAFs) by secreting substance P (SP). The anti-tumor strategy by targeting "SP-HSCs-HCC" axis might be an effective therapy to inhibit tumor growth and metastasis. Objective: In this study, we prepared novel liposomes (CUR-APR/HA&GA-LPs) modified with hyaluronic acid (HA) and glycyrrhetinic acid (GA) for co-delivery aprepitant (APR) and curcumin (CUR), in which APR was chosen to inhibit the activation of HSCs by blocking SP/neurokinin-1 receptor (NK-1R), and CUR was used to induce apoptosis of tumor cells. Results: To mimic the TME, we established "SP+HSCs+HCC" co-cultured cell model in vitro. The results showed that CUR-APR/HA&GA-LPs could be taken up by CAFs and HCC simultaneously, and inhibit tumor cell migration. Meanwhile, the "SP+m-HSCs+HCC" co-implanted mice model was established to evaluate the anti-tumor effect in vivo. The results showed that CUR-APR/HA&GA-LPs could inhibit tumor proliferation and metastasis, and reduce extracellular matrix (ECM) deposition and tumor angiogenesis, indicating a superior anti-HCC effect. Conclusion: Overall, the combination therapy based on HA&GA-LPs could be a potential nano-sized formulation for anti-HCC therapy.

Poor Pre-operative Nutritional Status Is a Risk Factor of Post-operative Infections in Patients With Gastrointestinal Cancer-A Multicenter Prospective Cohort Study.

Objective: This study aimed to assess the prognostic value of the Nutritional Risk Score 2002 (NRS2002) and patient-generated subjective global assessment (PG-SGA) for post-operative infections in patients with gastric cancer (GC) and colorectal cancer (CRC) who underwent curative surgery. Methods: This prospective study included 1,493 GC patients and 879 CRC patients who underwent curative surgery at 18 hospitals in China between April 2017 and March 2020. The NRS2002 and PG-SGA were performed on the day of admission. The relationship between the nutritional status of patients before surgery and post-surgical incidence of infection was analyzed using univariate and multiple logistic regression analyses. Results: According to NRS2002, the prevalence of nutritional risk was 51.1% in GC patients and 63.9% in CRC patients. According to the PG-SGA, 38.9% of GC patients and 54.2% of CRC patients had malnutrition. Approximately 4.4% of the GC patients and 9.9% of the CRC patients developed infectious complications after surgery. The univariate and multiple logistic regression analyses showed that the risk of infections was significantly higher in GC patients with a high nutritional risk score (NRS2002 ≥5) than in those with a low score (NRS2002 <3), and the PG-SGA score was identified as a predictor of post-operative infection complications of CRC. Conclusion: The pre-operative nutritional status of patients with GC or CRC has an impact on post-operative infection occurrence. NRS2002 ≥5 was a risk factor for post-operative infection in patients with GC, and the PG-SGA B/C was a predictor of infections in patients with CRC.

Effect of Early vs Late Supplemental Parenteral Nutrition in Patients Undergoing Abdominal Surgery: A Randomized Clinical Trial.

Importance: The effect of and optimal timing for initiating supplemental parenteral nutrition (SPN) remain unclear after major abdominal surgery for patients in whom energy targets cannot be met by enteral nutrition (EN) alone. Objective: To examine the effect of early supplemental parenteral nutrition (E-SPN) (day 3 after surgery) or late supplemental parenteral nutrition (L-SPN) (day 8 after surgery) on the incidence of nosocomial infections in patients undergoing major abdominal surgery who are at high nutritional risk and have poor tolerance to EN. Design, Setting, and Participants: A multicenter randomized clinical trial was conducted from April 1, 2017, to December 31, 2018, in the general surgery department of 11 tertiary hospitals in China. Participants were those undergoing major abdominal surgery with high nutritional risk and poor tolerance to EN (≤30% of energy targets from EN on postoperative day 2, calculated as 25 and 30 kcal/kg of ideal body weight daily for women and men, respectively) and an expected postoperative hospital stay longer than 7 days. Data analysis was performed from February 1 to October 31, 2020. Interventions: Random allocation to E-SPN (starting on day 3 after surgery) or L-SPN (starting on day 8 after surgery). Main Outcomes and Measures: The primary outcome was the incidence of nosocomial infections between postoperative day 3 and hospital discharge. Results: A total of 230 patients (mean [SD] age, 60.1 [11.2] years; 140 men [61.1%]; all patients were of Han race and Asian ethnicity) were randomized (115 to the E-SPN group and 115 to the L-SPN group). One patient in the L-SPN group withdrew informed consent before the intervention. The E-SPN group received more mean (SD) energy delivery between days 3 and 7 compared with the L-SPN group (26.5 [7.4] vs 15.1 [4.8] kcal/kg daily; P < .001). The E-SPN group had significantly fewer nosocomial infections compared with the L-SPN group (10/115 [8.7%] vs 21/114 [18.4%]; risk difference, 9.7%; 95% CI, 0.9%-18.5%; P = .04). No significant differences were found between the E-SPN group and the L-SPN group in the mean (SD) number of noninfectious complications (31/115 [27.0%] vs 38/114 [33.3%]; risk difference, 6.4%; 95% CI, -5.5% to 18.2%; P = .32), total adverse events (75/115 [65.2%] vs 82/114 [71.9%]; risk difference, 6.7%; 95% CI, -5.3% to 18.7%; P = .32), and rates of other secondary outcomes. A significant difference was found in the mean (SD) number of therapeutic antibiotic days between the E-SPN group and the L-SPN group (6.0 [0.8] vs 7.0 [1.1] days; mean difference, 1.0 days; 95% CI, 0.2-1.9 days; P = .01). Conclusion and Relevance: In this randomized clinical trial, E-SPN was associated with reduced nosocomial infections in patients undergoing abdominal surgery and seems to be a favorable strategy for patients with high nutritional risk and poor tolerance to EN after major abdominal surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT03115957.

Immediate vs. gradual advancement to goal of enteral nutrition after elective abdominal surgery: A multicenter non-inferiority randomized trial.

BACKGROUND & AIMS: The strategy of increasing the postoperative enteral nutrition dose to the target goal has not yet been clarified. This study aimed to determine whether an immediate goal-dose enteral nutrition (IGEN) strategy is non-inferior to a gradual goal-dose enteral nutrition (GGEN) strategy in reducing infections in patients undergoing abdominal surgery involving the organs of the digestive system. METHODS: This randomized controlled trial enrolled postoperative patients with nutritional risk screening 2002 scores ≥3 from 11 Chinese hospitals. Energy targets were calculated as 25 kcal/kg and 30 kcal/kg of ideal body weight for women and men, respectively. Patients were randomly assigned 1:1 to IGEN or GGEN group after enteral tolerance was confirmed (30% of the target on day 2). The IGEN group immediately started receiving 100% of the caloric requirements on day 3, while the GGEN group received 40% progressing to 80% of target on day 7. The primary endpoint was the infection rate until discharge, based on the intention-to-treat population. RESULTS: A total of 411 patients were enrolled and randomized to the IGEN and GGEN groups, and five patients did not receive the allocated intervention. A total of 406 patients were included in the primary analysis, with 199 and 207 in the IGEN and GGEN groups, respectively. Infection was observed in 17/199 (8.5%) in the IGEN group and 19/207 (9.2%) in the GGEN group, respectively (difference, -0.6%; [95% confidence interval (CI), -6.2%-4.9%]; P = 0.009 for non-inferiority test). There were significantly more gastrointestinal intolerance events with IGEN than with GGEN (58/199 [29.1%] vs. 32/207 [15.5%], P < 0.001). All other secondary endpoints were non-significant. CONCLUSIONS: Among postoperative patients at nutritional risk, IGEN was non-inferior to GGEN in regards to infectious complications. IGEN was associated with more gastrointestinal intolerance events. It showed that IGEN cannot be considered to be clinically directive. ClinicalTrials.gov (#NCT03117348).

Preparation of docetaxel-loaded, glycyrrhetinic acid-modified nanoparticles and their liver-targeting and antitumor activity.

Liver cancer is one of the most common malignancies worldwide and poses a serious threat to human health. The most important treatment method, liver cancer chemotherapy, is limited due to its high toxicity and poor specificity. Targeted drug delivery systems have emerged as novel therapeutic strategies that deliver precise, substantial drug doses to target sites via targeting vectors and enhance the therapeutic efficacy. In the present study, glycyrrhetinic acid-modified hyaluronic acid (GA-HA) was used as a carrier for the model drug docetaxel (DTX) to prepare DTX-loaded GA-HA nanoparticles (DTX/GA-HA-NPs). The results indicated that the DTX/GA-HA-NPs exhibited high monodispersity (particle dispersity index, 0.209±0.116) and desirable particle size (208.73±5.0 nm) and zeta potential (-27.83±3.14 mV). The drug loading capacity and encapsulation efficiency of the NPs were 12.59±0.68 and 85.38±4.62%, respectively. Furthermore, it was determined that FITC-GA-HA was taken up by cells and distributed in the cytoplasm. DTX and DTX/GA-HA (just the DTX delivered by the nanoparticle) aggregated and altered the structure of cellular microtubules. Compared with DTX alone, DTX/GA-HA-NPs had a stronger inhibitory effect on HepG2 cell proliferation and promoted apoptosis of HepG2 cells. All experimental results indicated that DTX/GA-HA-NPs were successfully prepared and had liver-targeting and antitumor activities in vitro, which provided a foundation for future in vivo studies of the antitumor effects of DTX/GA-HA-NPs.

Combined anti-hepatocellular carcinoma therapy inhibit drug-resistance and metastasis via targeting "substance P-hepatic stellate cells-hepatocellular carcinoma" axis.

Peripheral nerves have emerged as the important components in tumor microenvironment (TME), which could activate hepatic stellate cells (HSCs) by secreting substance P (SP), leading to hepatocellular carcinoma (HCC) invasion and metastasis. Herein, we proposed a novel anti-HCC concept of blocking "SP-HSCs-HCC" axis for omnidirectional inhibition of HCC development. To pursue this aim, the novel CAP/GA-sHA-DOX NPs were developed for targeted co-delivery of capsaicin (CAP) and doxorubicin (DOX) using glycyrrhetinic acid (GA) modified sulfated-HA (sHA) as nanocarriers. Among that, CAP could inhibit the activation of HSCs as an inhibitor of SP. Notably, to real mimic "SP-HSCs-HCC" axis for in vitro and in vivo evaluation, both "SP + LX-2+BEL-7402" co-cultured cell model and "SP + m-HSC + H22" co-implantation mice model were attempted for the first time. Furthermore, in vivo anti-HCC effects were performed in three different tumor-bearing models: subcutaneous implantation of H22 or "SP + m-HSC + H22", intravenous injection of H22 for lung metastasis, and orthotopic implantation of H22 for primary HCC. Our results showed that CAP/GA-sHA-DOX NPs could be efficiently taken up by tumor cells and activated HSCs (aHSCs) simultaneously, and effectively inhibit tumor drug-resistance and migration by blocking SP-induced HSCs activation. In addition, CAP/GA-sHA-DOX NPs exhibited low ECM deposition, less tumor angiogenesis, and superior in vivo anti-HCC effects. The anti-HCC mechanisms revealed that CAP/GA-sHA-DOX NPs could down-regulate the expression level of Vimentin and P-gp, reverse epithelial-mesenchymal transition (EMT) of tumor cells. In brief, the nano-sized combination therapy based on GA-sHA-DOX polymers could effectively inhibit drug-resistance and metastasis of HCC by blocking "SP-HSCs-HCC" axis, which provides a promising approach for cancer therapy.

Laparoscopic gastrectomy for elderly gastric-cancer patients: comparisons with laparoscopic gastrectomy in non-elderly patients and open gastrectomy in the elderly.

BACKGROUND: The benefits of laparoscopic gastrectomy (LG) in elderly gastric-cancer patients still remain unclear. The purpose of this study was to evaluate the feasibility and safety of LG in elderly gastric-cancer patients. METHODS: We retrospectively evaluated patients who underwent LG or open gastrectomy (OG) between June 2009 and July 2015 in a single high-volume center. We compared surgical, short-term, and long-term survival outcomes among an elderly (≥70 years old) LG (ELG) group (n = 114), a non-elderly (<70 years old) LG (NLG) group (n = 740), and an elderly OG (EOG) group (n = 383). RESULTS: Except for extended time to first flatus, the surgical and short-term outcomes of the ELG group were similar to those of the NLG group. The ELG group revealed comparable disease-specific survival (DSS) rates to the NLG group (64.9% vs 66.2%, P = 0.476), although the overall survival (OS) rate was lower (57.0% vs 65.5%, P < 0.001) in the ELG group than in the NLG group. The ELG group showed longer operation time than the EOG group (236.4 ± 77.3 vs 179 ± 52.2 min, P < 0.001). The ELG group had less estimated blood loss (174.0 ± 88.4 vs 209.3 ± 133.8, P = 0.008) and shorter post-operative hospital stay (8.3 ± 2.5 vs 9.2 ± 4.5, P = 0.048) than the EOG group. The severity of complications was similar between the ELG and NLG groups. Multivariate analysis confirmed that LG was not a risk factor for post-operative complications. CONCLUSIONS: LG is a feasible and safe procedure for elderly patients with acceptable short- and long-term survival outcomes.

Multiple intravenous tranexamic acid doses in total knee arthroplasty in patients with rheumatoid arthritis: a randomized controlled study.

BACKGROUND: We aimed to determine the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) on perioperative blood loss in patients with rheumatoid arthritis (RA) who had undergone primary unilateral total knee arthroplasty (TKA). METHODS: For this single-center, single-blind randomized controlled clinical trial, 10 male and 87 female participants with RA, aged 50-75 years, who underwent unilateral primary TKA were recruited. The patients received one dose of 1 g IV-TXA 10 min before skin incision, followed by articular injection of 1.5 g tranexamic acid after cavity suture during the surgery. The patients were randomly assigned (1:1) into two groups and received an additional single dose of IV-TXA (1 g) for 3 h (group A) or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group B) postoperatively. Primary outcomes were total blood loss (TBL), hidden blood loss (HBL), and maximum hemoglobin (Hb) level decrease. Secondary outcomes were transfusion rate and D-dimer levels. All parameters were measured postoperatively during inpatient hospital stay. RESULTS: The mean TBL, HBL, and maximum Hb level decrease in group B (506.1 ± 227.0 mL, 471.6 ± 224.0 mL, and 17.5 ± 7.7 g/L, respectively) were significantly lower than those in group A (608.8 ± 244.8 mL, P = 0.035; 574.0 ± 242.3 mL, P = 0.033; and 23.42 ± 9.2 g/L, P = 0.001, respectively). No episode of transfusion occurred. The D-dimer level was lower in group B than in group A on postoperative day 1 (P <  0.001), and the incidence of thromboembolic events was similar between the groups (P > 0.05). CONCLUSION: In patients with RA, three doses of postoperative IV-TXA further facilitated HBL and Hb level decrease without increasing the incidence of adverse events in a short period after TKA. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry ( ChiCTR1900025013 ).

The effectiveness of electro-acupuncture combined with dyclonine hydrochloride in relieving the side effects of gastroscopy: a controlled trial.

BACKGROUND: The present study aimed to explore the effectiveness of electro-acupuncture (EA) in combination with a local anesthetic used in Western medicine in preventing the side effects of gastroscopy. METHODS: A sample group of 150 patients were divided into three groups based on treatment methods: an EA group, a dyclonine hydrochloride mucilage group, and a combined treatment group. In the EA group, EA stimulation was given at the Hegu, Neiguan, and Zusanli acupoints; in the dyclonine hydrochloride mucilage group, patients took 10 mL of dyclonine hydrochloride mucilage orally; in the combined treatment group, prevention of side effects was attempted by administration of both acupuncture and oral local anesthetic. The incidences of nausea, emesis, salivation, cough, restlessness, and breath holding during gastroscopy were observed and recorded for the three groups. Mean arterial pressure, heart rate, and oxygen saturation were recorded before the examination, and changes in these measures were recorded as the gastroscope passed through the pylorus and after the examination. The visual analogue scale (VAS) values of nausea and emesis, the rate of successful first-pass intubation, and the time of gastroscopy were also recorded. Statistical analysis was performed using R-3.5.3 software. RESULTS: Incidences of side effects (e.g., nausea, emesis, salivation, restlessness, and breath holding) during the examination were lower in the combined treatment group than in the EA group and the dyclonine hydrochloride mucilage group (P<0.05 and P<0.01, respectively). Furthermore, the changes in heart rate and oxygen saturation when the gastroscope passed through the pylorus and after the examination were better in the combined treatment group than in the EA group and dyclonine hydrochloride mucilage group (P<0.01). The VAS values of nausea and emesis, the first-pass success rate, and examination duration were also better for the combined treatment group than for the other two groups (P<0.05 and P<0.01). CONCLUSIONS: EA combined with local anesthesia with dyclonine hydrochloride mucilage can alleviate side effects during gastroscopy, reduce patient pain, and improve the efficiency of the procedure.

Protective effects of resveratrol liposomes on mitochondria in substantia nigra cells of parkinsonized rats.

BACKGROUND: Parkinson's disease (PD) is a central nervous system degenerative disease. The progressive death of dopaminergic neurons is closely correlated to mitochondrial dysfunction. Resveratrol contains three hydroxyl groups, and has a strong neuroprotective effect. This study aimed to investigate the protective effect of resveratrol liposome on mitochondria of substantia nigra cells in Parkinsonized rats through experiment. METHODS: The investigators used 6-hydroxydopamine to establish the Parkinsonized rat model, and used resveratrol liposome from Polygonum cuspidatum (20 mg·kg-1) for gavage, up to a total volume of 1 mL, once-daily, for two weeks. After treatment, the levels of mitochondrial membrane potential, mitochondrial complexes I-IV, mitochondrial cytochrome C, apoptosis-inducing factor (AIF), PTEN-induced putative kinase 1 (PINK1), tumor necrosis factor-receptor-associated protein 1 (TRAP1) and phosphorylated TRAP1 in rat mesencephalic cells were detected according to the operation instructions of the kits. RESULTS: After two weeks of treatment, resveratrol liposomes could significantly enhance the activity of mitochondrial electron transfer chain complex I in the substantia nigra cells of Parkinsonized model rats, promote the expression of complex I subcomponent MT-ND1-37kD, improve mitochondrial membrane potential, inhibit the release of mitochondrial cytochrome C and apoptotic inducible factor, enhance the expression of mitochondrial functional protein PINK1, increase the phosphorylated TRAP1 level, and elevate the phosphorylated TRAP1/TRAP1 ratio. CONCLUSIONS: Resveratrol liposome has positive effects on mitochondria in substantia nigra cells of Parkinsonized rats, and may be one of its pharmacological mechanisms.

Galactose Modified Liposomes for Effective Co-Delivery of Doxorubicin and Combretastatin A4.

BACKGROUND: Tumor angiogenesis plays a crucial role in tumor development, and recent efforts have been focused on combining proapoptotic and antiangiogenic activities to enhance antitumor therapy. METHODS: In this study, galactose-modified liposomes (Gal-LPs) were prepared for co-delivery of doxorubicin (DOX) and combretastatin A4 phosphate (CA4P). The co-cultured system composed of BEL-7402 and human umbilical vein endothelial cells (HUVEC) cells was established to effectively evaluate in vitro anti-tumor activity through cell viability and cell migration assay. Furthermore, both in vivo bio-distribution and anti-hepatoma effect of DOX&CA4P/Gal-LPs were investigated on H22 tumor cell-bearing mice. RESULTS: The results showed that DOX&CA4P/Gal-LPs were spherical with a mean particle size of 143 nm, and could readily be taken up by BEL-7402 cells. Compared with a mixture of free DOX and CA4P, the DOX&CA4P/Gal-LPs were more effective in inhibiting cell migration and exhibited stronger cytotoxicity against BEL-7402 cells alone or a co-cultured system. The in vitro studies showed that the co-cultured system was a more effective model to evaluate the anti-tumor activity of combination therapy. Moreover, DOX&CA4P/Gal-LPs exhibited a greater anti-hepatoma effect than other drug formulations, indicating that Gal-LPs could promote drug accumulation in the tumor region and improve the anti-tumor activity. CONCLUSION: Gal-LPs co-loaded with chemotherapeutic and antiangiogenic drugs are a promising strategy for anti-hepatoma therapy.

Effect of Multiple Doses of Intravenous Tranexamic Acid on Perioperative Blood Loss in Total Knee Arthroplasty: A Randomized Controlled Study.

OBJECTIVE: To identify the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) following primary total knee arthroplasty (TKA) with a tourniquet. METHODS: This is a single-blind randomized controlled study that recruited osteoarthritis patients who had undergone primary unilateral TKA from May 2019 to May 2020 at our medical center. A total of 300 patients were randomly divided into three groups to receive: one dose (1 g) of IV-TXA before skin incision combined with one dose (1.5 g) of intra-articular tranexamic acid（IA-TXA) followed by a single dose of IV-TXA (1 g) for 3 h (group A); two doses of IV-TXA (1 g) for 3 and 6 h (group B); or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group C) postoperatively. TKA with a tourniquet was performed by the same surgical team. The primary outcomes were total blood cell loss (TBL), hidden blood loss (HBL), maximum hemoglobin (Hb) drop, and transfusion rate. Secondary outcomes were levels of C-reactive protein (CRP) and D-dimer, and the incidence of postoperative complications. One-way analysis of variance, subgroup analysis, and multivariate correlation analysis were used to calculate the differences among the three groups. RESULTS: The study included 56 male and 244 female patients aged 60-80 years. The mean TBL, the mean HBL, and the maximum Hb drop in group C (471.2 ± 190.6 mL, 428.4 ± 190.3 mL, and 21.2 ± 3.8 g/L, respectively) were significantly lower than those in groups B (563.4 ± 224.6 mL, P = 0.030; 519.9 ± 226.4 mL, P = 0.033; and 23.2 ± 4.1 g/L, P = 0.001, respectively), and A (651.6 ± 254.1 mL, P < 0.001; 607.1 ± 254.3 mL, P < 0.001; and 25.1 ± 4.3 g/L, P < 0.001, respectively). No transfusions were required. The postoperative acute inflammatory reaction was less problematic for patients in Group C, and the incidence of thromboembolic events was similar among the groups (P > 0.05). In addition, there were positive correlations between the HBL and the tourniquet inflation time (r = 0.844, P < 0.001). Similarly, the level of CRP on POD1 (r = 0.393, P < 0.001) and POD3 (r = 0.149, P = 0.010), and the level of D-dimer on POD1 (r = 0.382, P < 0.001) were positively correlated with the HBL. CONCLUSION: Three doses of postoperative IV-TXA decreased blood loss and diminished the postoperative inflammatory and fibrinolytic response more than a single dose or two doses in elderly patients following TKA without increasing the incidence of adverse events.

Beware Pathological Findings of the Stomach in Patients Undergoing Bariatric Surgery: a Systematic Review and Meta-analysis.

Abnormal anatomic findings are a major concern before performing bariatric surgery, while pathological changes are considered less often. The present study aimed to investigate the incidences of gastric lesions warranting follow-up in patients undergoing bariatric surgery. Meta-analyses were conducted to calculate the pooled incidences of gastric lesions in patients undergoing bariatric surgery. Fifty-nine studies including 32,789 patients were included: 26 on endoscopic biopsy, 26 on pathological findings of the excised specimen, five on the intraoperative exploration results, and two on both preoperative endoscopy and postoperative specimen. Generally, atrophic gastritis (3.05% (95% CI (confidence interval) 1.53-6.09)), intestinal metaplasia (2.44% (95% CI 1.76-3.25)), and GIST (gastrointestinal stromal tumor) (0.45% (95% CI 0.31-0.60)) were not rarely found. Routine preoperative endoscopy was applied in 16 studies, and the pooled incidences of atrophic gastritis and intestinal metaplasia were 2.64% (95% CI 0.78-8.9) and 2.70% (95% CI 0.9-5.42), respectively. Hp. (Helicobacter pylori) screening and eradication were routinely performed in 10 studies, and that was related to a reduced incidence of atrophic gastritis (0.94% (95% CI 0.03-2.92)) vs. 4.31% (95% CI 2.01-9.23). GIST was more likely to be found by intraoperative exploration than by preoperative endoscopy (0.68% (95% CI 0.50-0.93) vs. 0.23% (95% CI 0.11-0.52)). Patients undergoing bariatric surgery demonstrated non-negligible incidences of gastric pathologies warranting follow-up. Preoperative endoscopy and careful intraoperative exploration should be routinely performed, and Hp. screening and eradication are suggested before endoscopy. In condition that such findings are detected, sleeve gastrectomy may be preferred over Roux-en-Y gastric bypass.

Risk Factors and Clavien-Dindo Classification of Postoperative Complications After Laparoscopic and Open Gastrectomies for Gastric Cancer: A Single-Center, Large Sample, Retrospective Cohort Study.

BACKGROUND: Laparoscopy has been increasingly used for the surgery of gastric cancer. However, the postoperative complications are still under-investigated and the short-term results of laparoscopic gastrectomy remain controversial. This study aimed to explore the differences of postoperative complications between laparoscopic and open radical gastrectomies in patients with gastric cancer through the large sample size, retrospective cohort study, and evaluate the safety of laparoscopy in patients who underwent radical gastrectomy. PATIENTS AND METHODS: A total of 2,966 patients with gastric cancer (TNM I~III) who underwent laparoscopy or open gastrectomy from February 2009 to March 2016 were enrolled in this study. Complications were categorized according to the Clavien-Dindo classification. The incidence and severity of complications between laparoscopic and open gastrectomy were compared using one-to-three propensity score matching (PSM) analysis. Logistic regression analyses were performed to identify risk factors related to postoperative complications. RESULTS: A total of 2,966 patients were included in the study, including 687 (23.2%) in the LG (Laparoscopy gastrectomies) group and 2,279 (76.8%) in the OG (open gastrectomies) group. After PSM, a well-balanced cohort of 2,373 patients (676 cases in the LG group and 1,697 cases in the OG group) was further analyzed. The results showed that the incidence of overall complications in the LG group was significantly less than the OG group (15.4% vs 20.8%, P=0.003). However, the severe complications of the LG group showed no difference towards the OG group (5.8% vs 5.8%, P=0.952). Multivariate analysis revealed that laparoscopic surgery is a protective factor for the reduction of postoperative complications. Age ≥60 years, ASA classification IIIc and estimated blood loss ≥200 mL were confirmed as independent risk factors of overall complications. CONCLUSION: Compared with traditional open gastrectomy, LG is safe and feasible with less trauma and fewer complications for patients with gastric cancer.