Pelvic Floor Peritoneum Closure Reduces Severe Postoperative Complications in Rectal Cancer Patients After Laparoscopic Anterior Rectal Resection.

BACKGROUND: Laparoscopic anterior rectal resection (LAR) is a commonly performed surgery for rectal cancer patients. Pelvic floor peritoneum closure (PC), a vital procedure in conventional anterior rectal resection, is not routinely performed in LAR. STUDY DESIGN: A total of 1118 consecutive patients with rectal cancer receiving LAR were included in this retrospective study. Patients were allocated into the PC group and the non-PC group. The occurrence of postoperative complications was compared between the 2 groups. Influential factors in anastomotic leakage (AL) were explored using univariate and multivariate logistic regression. RESULTS: There was no difference between the groups in terms of baseline characteristics. The occurrence of postoperative complications was similar between the groups. The PC group had significantly shorter postoperative hospitalization and longer operation duration compared with the non-PC group. The occurrences of Clavien-Dindo (CD) III-IV complications, CD III-IV AL, and reoperation were significantly lower in the PC group than the non-PC group. PC and a protective ileostomy were independent protective factors for CD III-IV AL. CONCLUSION: PC could reduce the occurrence of CD III-IV complications, especially CD III-IV AL, and the rate of secondary surgery, especially in patients with a lower body mass index and patients who did not receive protective ileostomies.

Long-term outcomes of single-incision plus one-port laparoscopic surgery versus conventional laparoscopic surgery for rectosigmoid cancer: a randomized controlled trial.

BACKGROUND: Though our previous study has demonstrated that the single-incision plus one-port laparoscopic surgery (SILS + 1) is safe and feasible for sigmoid colon and upper rectal cancer and has better short-term outcomes compared with conventional laparoscopic surgery (CLS), the long-term outcomes of SILS + 1 remains uncertain and are needed to evaluated by an RCT. METHODS: Patients with clinical stage T1-4aN0-2M0 rectosigmoid cancer were enrolled. The participants were randomly assigned to either SILS + 1 (n = 99) or CLS (n = 99). The 3-year DFS, 5-year OS, and recurrence patterns were analyzed. RESULTS: Between April 2014 and July 2016, 198 patients were randomly assigned to either the SILS + 1 group (n = 99) or CLS group (n = 99). The median follow-up in the SILS + 1 group was 64.0 months and in CLS group was 65.0 months. The 3-year DFS was 87.8% (95% CI, 81.6-94.8%) in SILS + 1 group and 86.9% (95% CI, 81.3-94.5%) in CLS group (hazard ratio: 1.09 (95% CI, 0.48-2.47; P = 0.84)). The 5-year OS was 86.7% (95% CI,79.6-93.8%) in the SILS + 1 group and 80.5% (95% CI,72.5-88.5%) in the CLS group (hazard ratio: 1.53 (95% CI, 0.74-3.18; P = 0.25)). There were no significant differences in the recurrence patterns between the two groups. CONCLUSIONS: We found no significant difference in 3-year DFS and 5-year OS of patients with sigmoid colon and upper rectal cancer treated with SILS + 1 vs. CLS. SILS + 1 is noninferior to CLS when performed by expert surgeons. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02117557 (registered on 21/04/2014).

Effect of Argatroban Plus Intravenous Alteplase vs Intravenous Alteplase Alone on Neurologic Function in Patients With Acute Ischemic Stroke: The ARAIS Randomized Clinical Trial.

Importance: Previous studies suggested a benefit of argatroban plus alteplase (recombinant tissue-type plasminogen activator) in patients with acute ischemic stroke (AIS). However, robust evidence in trials with large sample sizes is lacking. Objective: To assess the efficacy of argatroban plus alteplase for AIS. Design, Setting, and Participants: This multicenter, open-label, blinded end point randomized clinical trial including 808 patients with AIS was conducted at 50 hospitals in China with enrollment from January 18, 2019, through October 30, 2021, and final follow-up on January 24, 2022. Interventions: Eligible patients were randomly assigned within 4.5 hours of symptom onset to the argatroban plus alteplase group (n = 402), which received intravenous argatroban (100 µg/kg bolus over 3-5 minutes followed by an infusion of 1.0 µg/kg per minute for 48 hours) within 1 hour after alteplase (0.9 mg/kg; maximum dose, 90 mg; 10% administered as 1-minute bolus, remaining infused over 1 hour), or alteplase alone group (n = 415), which received intravenous alteplase alone. Both groups received guideline-based treatments. Main Outcomes and Measures: The primary end point was excellent functional outcome, defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 1 at 90 days. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 817 eligible patients with AIS who were randomized (median [IQR] age, 65 [57-71] years; 238 [29.1%] women; median [IQR] National Institutes of Health Stroke Scale score, 9 [7-12]), 760 (93.0%) completed the trial. At 90 days, 210 of 329 participants (63.8%) in the argatroban plus alteplase group vs 238 of 367 (64.9%) in the alteplase alone group had an excellent functional outcome (risk difference, -1.0% [95% CI, -8.1% to 6.1%]; risk ratio, 0.98 [95% CI, 0.88-1.10]; P = .78). The percentages of participants with symptomatic intracranial hemorrhage, parenchymal hematoma type 2, and major systemic bleeding were 2.1% (8/383), 2.3% (9/383), and 0.3% (1/383), respectively, in the argatroban plus alteplase group and 1.8% (7/397), 2.5% (10/397), and 0.5% (2/397), respectively, in the alteplase alone group. Conclusions and Relevance: Among patients with acute ischemic stroke, treatment with argatroban plus intravenous alteplase compared with alteplase alone did not result in a significantly greater likelihood of excellent functional outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT03740958.

CT Appearance Pattern After Stereotactic Body Radiation Therapy Predicts Outcomes in Early-Stage Non-Small-Cell Lung Cancer.

BACKGROUNDS: Computed tomography (CT) appearance pattern after lung tumor stereotactic body radiation therapy(SBRT) might predicts survival. This study aimed to investigate the correlation between CT appearance pattern after SBRT and outcomes in patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: Clinical data of inoperable patients with early-stage NSCLC undergoing SBRT were retrospectively analyzed from 2012 to 2015 at the Zhejiang Cancer Hospital. The relationship between CT appearance pattern after SBRT and patient's survival was analyzed. RESULTS: The data from 173 patients with early-stage lung cancer treated with SBRT were analyzed. One month after SBRT, diffuse consolidation was seen in 17 patients, patchy consolidation in 28 patients, diffuse ground-glass opacity (GGO) in 10 patients, and patchy GGO in 22 patients. The survival time was significantly longer in the "no evidence of increased density" group compared with the "consolidation or GGO" group [2-year overall survival (OS) rate, 96.1% vs 89.3%; hazard ratio (HR), 0.36; 95% confidence interval (CI), 0.16-0.85; P = 0.015]. A similar trend was found in the progression-free survival (PFS) analysis (2-year PFS rate, 91.3% vs 85.0%; HR, 0.35; 95% CI, 0.13-0.95; P = 0.015) and distant metastasis free survival(DMFS) (2-year DMFS rate, 93.3% vs 87.1%; HR, 0.41; 95% CI, 0.20-0.86; P = 0.031). However, no significant difference was found in recurrence-free survival between the two groups (P = 0.212). CONCLUSIONS: One month after SBRT, the radiological change "no evidence of increased density" was prevalent. The OS, PFS, and DMFS were significantly longer in the "no evidence of increased density" group compared with the "consolidation or GGO" group. Further studies are needed to validate these findings.

Recombinant human insulin-like growth factor-1 promotes osteoclast formation and accelerates orthodontic tooth movement in rats.

BACKGROUND: IGF-1 may be an important factor in bone remodeling, but its mechanism of action on osteoclasts during orthodontic tooth movement is complex and unclear. METHODOLOGY: The closed-coil spring was placed between the left maxillary first molar and upper incisors with a force of 50 g to establish an orthodontic movement model. Eighty SD rats were randomized to receive phosphate buffer saline or 400 ng rhIGF-1 in the lateral buccal mucosa of the left maxillary first molar every two days. Tissue sections were stained for tartrate-resistant acidic phosphatase (TRAP), the number of TRAP-positive cells was estimated and tooth movement measured. RESULTS: The rhIGF-1 group exhibited evidential bone resorption and lacuna appeared on the alveolar bone compared to the control group. Moreover, the number of osteoclasts in compression side of the periodontal ligament in the rhIGF-1 group peaked at day 4 (11.37±0.95 compared to 5.28±0.47 in the control group) after the orthodontic force was applied and was significantly higher than that of the control group (p<0.01). Furthermore, the distance of tooth movement in the rhIGF-1 group was significantly larger than that of the control group from day 4 to day 14 (p<0.01), suggesting that rhIGF-1 accelerated orthodontic tooth movement. CONCLUSION: Our study has showed that rhIGF-1 could stimulate the formation of osteoclasts in the periodontal ligament, and accelerate bone remodeling and orthodontic tooth movement.

Effect of single-incision plus one port laparoscopic surgery assisted with enhanced recovery after surgery on colorectal cancer: study protocol for a single-arm trial.

BACKGROUND: Studies have proved that the enhanced recovery after surgery (ERAS) protocol can significantly improve the recovery course of patients during the perioperative period. The application of minimally invasive surgery is a critical component of ERAS protocol. Single-incision plus one port laparoscopic surgery (SILS plus one) could achieve further minimally invasive surgical results than conventional laparoscopic surgery (CLS). The objective of this trial is to evaluate the safety and feasibility of SILS plus one with ERAS protocol in colorectal cancer. METHODS: This is a prospective, single-center, open-label, single-arm trial. A total of 120 eligible patients with colorectal cancer will receive SILS plus one followed by the ERAS management during the perioperative period. The primary endpoint is postoperative hospital stay. The secondary endpoints include rehabilitative rate of the fourth postoperative day, postoperative medical cost, postoperative pain score, postoperative recovery indexes, inflammatory immune response indexes, compliance with ERAS measures, 6 min postoperative walking test (6MWT), hospital readmissions, and early postoperative complications. DISCUSSION: This trial will be the first to evaluate the short-term outcomes of SILS plus one assisted with ERAS protocol for patients with colorectal cancer and will provide valuable clinical evidence on the benefit of the combination of these two techniques, hopefully, to provide patients with more safe, economic, feasible, and rapid surgery and perioperative strategies. TRIAL REGISTRATION: Clinical Trial Registry, NCT0426829. Registered February 15, 2020 (https://clinicaltrials.gov/ct2/show/NCT04268290).

Recombinant human insulin-like growth factor-1 promotes osteoclast formation and accelerates orthodontic tooth movement in rats

Abstract Background: IGF-1 may be an important factor in bone remodeling, but its mechanism of action on osteoclasts during orthodontic tooth movement is complex and unclear. Methodology: The closed-coil spring was placed between the left maxillary first molar and upper incisors with a force of 50 g to establish an orthodontic movement model. Eighty SD rats were randomized to receive phosphate buffer saline or 400 ng rhIGF-1 in the lateral buccal mucosa of the left maxillary first molar every two days. Tissue sections were stained for tartrate-resistant acidic phosphatase (TRAP), the number of TRAP-positive cells was estimated and tooth movement measured. Results: The rhIGF-1 group exhibited evidential bone resorption and lacuna appeared on the alveolar bone compared to the control group. Moreover, the number of osteoclasts in compression side of the periodontal ligament in the rhIGF-1 group peaked at day 4 (11.37±0.95 compared to 5.28±0.47 in the control group) after the orthodontic force was applied and was significantly higher than that of the control group (p<0.01). Furthermore, the distance of tooth movement in the rhIGF-1 group was significantly larger than that of the control group from day 4 to day 14 (p<0.01), suggesting that rhIGF-1 accelerated orthodontic tooth movement. Conclusion: Our study has showed that rhIGF-1 could stimulate the formation of osteoclasts in the periodontal ligament, and accelerate bone remodeling and orthodontic tooth movement.

Exosomes are the novel players involved in the beneficial effects of exercise on type 2 diabetes.

Exosomes contain regulatory signals such as lipids, proteins, and nucleic acids which can be transferred to adjacent or remote cells to mediate cell-to-cell communication. Exercise is a positive lifestyle for metabolic health and a nonpharmacological treatment of insulin resistance and metabolic diseases. Moreover, exercise is a stressor that induces cellular responses including gene expression and exosome release in various types of cells. Exosomes can carry the characters of parent cells by their modified cargoes, representing novel mechanisms for the effects of exercise. Here, we present a review of exosomes as the perspective players in mediating exercise's beneficial impacts on type 2 diabetes (T2D).

Somatic mutation profiling of liver and biliary cancer by targeted next generation sequencing.

Liver and biliary cancers are highly lethal cancer types lacking effective treatments. The somatic mutations, particularly those with low mutant allele frequencies, in Chinese patients with liver and biliary cancer have not been profiled, and the frequency of patients benefiting from targeted therapy has not been studied. The present study evaluated the tumor tissues of 45 Chinese patients with hepatocellular carcinoma (HCC) and 12 Chinese patients with biliary tract cancer (BTC) by targeted next generation sequencing, with an average coverage of 639×, to identify alterations in 372 cancer-related genes. A total of 263 variants were identified in 139 genes, with 85.6% of these variants not previously reported in the Catalogue Of Somatic Mutations In Cancer database, and the mutation profile was different from the current datasets, including The Cancer Genome Atlas dataset and the National Cancer Center Japan (NCC_JP) dataset. Patients with hepatitis B virus (HBV) infection harbored more mutations than those without HBV infection, and the mutations in HBV carriers occurred preferentially in genes involved in vascular endothelial growth factor signaling pathways. Mutations in fibroblast growth factor and RAS signaling pathways were enriched in patients with cirrhosis, and alterations in interleukin and transforming growth factor signaling pathways were more frequently identified in individuals with abnormal bilirubin expression. Of all the patients, 7% exhibited variants in the target of sorafenib, and 42% harbored variants in the targets of drugs that have been approved to treat other types of cancer. These findings indicate diverse HCC/BTC variants patterns in different populations, and that the mutation load and patterns are correlated with clinical features. Further clinical studies are now warranted to evaluate the efficacies of other targeted drugs besides sorafenib in the treatment of patients with liver and biliary cancer.

Repetitive magnetic stimulation promotes the proliferation of neural progenitor cells via modulating the expression of miR-106b.

Increasing evidence shows that repetitive transcranial magnetic stimulation (rTMS) promotes neurogenesis and the expression of microRNA (miR)­106b. The present study investigated whether rTMS promotes the proliferation of neural progenitor cells (NPCs) and whether the effect is associated with the expression of miR­106b. NPCs were cultured from the rat hippocampus and exposed to rTMS daily, comprising 1,000 stimuli for 3 days at 10 Hz, with 1.75 T output. The proliferation ability of the NPCs was revealed by EdU staining, and the levels of miR­106b and downstream gene p21 in the NPCs were measured by reverse transcription­quantitative polymerase chain reaction and western blot analyses. For analysis of the mechanism, the NPCs were transfected with Lenti­miR­106b or small interfering RNAs prior to rTMS. The results showed that: i) rTMS increased NPC proliferation, as revealed by the increased proportion of EdU­positive cells; ii) rTMS was able to upregulate the expression of miR­106b and downregulate the level of p21 in NPCs; iii) overexpression of miR­106b further enhanced the effects of rTMS, whereas knockdown of miR­106b had the opposite effects. Taken together, these data indicated that rTMS can promote NPC proliferation by upregulating the expression of miR­106b and possibly inhibiting the expression of p21.

[Effect of local injection of rhTGF-α1 on osteoclasts during orthodontic tooth movement in rats].

PURPOSE: To investigate the effect of exogenous TGF-ß1 on improving periodontal tissues remodeling during orthodontic tooth movement in rats. METHODS: Eighty male SD rats were randomly divided into 2 groups. Rats in the experimental group were injected respectively with rhTGF-ß1 in dosages of 0.1 mL (5 ng/mL) in the buccal submucosal area of the molar every other day, while rats in the control group received equivalent volumes of PBS. Each group (n=40) was subdivided equally into 5 subgroups. An orthodontic appliance, consisting of a 5 mm nickel titanium closed coil spring, was ligated between the maxillary left incisor and first molar of each rat to deliver an initial force of 0.49N. Eight rats in each subgroup were sacrificed at one of the five time points (1, 4, 7, 10 and 14 days) after appliance placement. The distance of the tooth movement was measured by using stereomicroscope. Tissue sections around the first maxillary left molar were stained with tartrate-resistant acid phosphatase (TRAP) histochemistry to analyze the changes of the amount and distribution of osteoclasts on the compression side of tooth. Statistical analysis was performed using SPSS 17.0 software package. RESULTS: Molars treated with rhTGF-ß1 moved mesially more rapidly than the control group. The distance of tooth movement of the experimental group showed a significant increase compared with the control group at day 7 (P<0.05) and significant increase compared with the control group at day 10 and 14 (P<0.01). The number of TRAP positive cells appearing in the periodontal ligament space on the pressure side of the alveolar bone were increased markedly in experimental group. There were statistically significant differences in the amount of osteoclasts between experimental and control groups (P<0.01). CONCLUSIONS: Local injection of rhTGF-ß1 in the periodontal tissues can accelerate orthodontic tooth movement via enhancing the numbers of osteoclasts. At the histologic level, increased numbers of mononuclear osteoclasts are recruited and activated, resulting in greater amounts of alveolar bone resorption on the pressure side of the periodontal ligament.

Perspectives on a combined test of multi serum biomarkers in China: towards screening for and diagnosing hepatocellular carcinoma at an earlier stage.

China has 50% of the worldwide hepatocellular carcinoma (HCC) cases, and the HBV-related cases accounts for approximately 85%. Over the past few decades, although a series of standardized management methods for HCC has been implemented in China, most HCC patient in China still suffered from advanced-stage disease, in consequence, reducing the opportunity of curable treatment that can be offered to achieve long-term disease-free survival for HCC patient. Accordingly, strategies including screening and diagnose HCC at an earlier stage are urgently needed in China. In this study, the current status, challenges, and prospects of early detection of HCC in China have been analyzed. The result indicated the need for using multi serum biomarkers for early HCC detection. During the past ten years, the research on the clinical usefulness of novel serum biomarkers of des-γ-carboxy-prothrombin (DCP), Dickkopf-1 (DKK1) and Midkine (MDK) in early HCC detection for Chinese patients found that the novel serum biomarker can complete the measurement of α-fetoprotein (AFP) in the diagnosis process of HCC, particularly for the patient with negative AFP with/or at an early stage. More large-scale, multi-center studies are expected to be performed in China to provide further evidence, and using novel and reliable serum biomarkers to complement AFP as a new trend is expected to be extensively used in clinical practice to facilitate early detection for those patients with HCC in China.

Ex-situ liver surgery without veno-venous bypass.

AIM: To evaluate the results of hepatic resection with ex-situ hypothermic perfusion and without veno-venous bypass. METHODS: In 3 patients with liver tumor, the degree of the inferior vena cava and/or main hepatic vein involvement was verified when the liver was dissociated in the operation. It was impossible to resect the tumors by the routine hepatectomy, so the patients underwent ex-situ liver surgery, vein cava replacement and hepatic autotransplantation without veno-venous bypass. All surgical procedures were carried out or supervised by a senior surgeon. A retrospective analysis was performed for the prospectively collected data from patients with liver tumor undergoing ex-situ liver surgery, vein cava replacement and hepatic autotransplantation without veno-venous bypass. We also compared our data with the 9 cases of Pichlmayr's group. RESULTS: Three patients with liver tumor were analysed. The first case was a 60-year-old female with a huge haemangioma located in S1, S4, S5, S6, S7 and S8 of liver; the second was a 64-year-old man with cholangiocarcinoma in S1, S2, S3 and S4 and the third one was a 55-year-old man with a huge cholangiocarcinoma in S1, S5, S7 and S8. The operation time for the three patients were 6.6, 6.4 and 7.3 h, respectively. The anhepatic phases were 3.8, 2.8 and 4.0 h. The volume of blood loss during operation were 1200, 3100, 2000 mL in the three patients, respectively. The survival periods without recurrence were 22 and 17 mo in the first two cases. As for the third case complicated with postoperative hepatic vein outflow obstruction, emergency hepatic vein outflow extending operation and assistant living donor liver transplantation were performed the next day, and finally died of liver and renal failure on the third day. Operation time (6.7 ± 0.47 h vs 13.7 ± 2.6 h) and anhepatic phase (3.5 ± 0.64 h vs 5.7 ± 1.7 h) were compared between Pichlmayr's group and our series (P = 0.78). CONCLUSION: Ex-situ liver resection and liver autotransplantation has shown a potential for treatment of complicated hepatic neoplasms that are unresectable by traditional procedures.

[Combined effects of platelet-derived growth factor-BB and insulin-like growth factor-I on the expression of integrin (beta 3 protein in periodontal ligament cells of rats during orthodontic tooth movement].

OBJECTIVE: To investigate the combined effects of platelet-derived growth factor-BB (PDGF-BB) and insulin-like growth factor-I (IGF-I) on the expression of integrin (beta3 protein in the periodontal tissues of the compressing side of orthodontic tooth in rats. METHODS: Establishing orthodontic movement model in Sprague-Dawley rats, which were injected with 10 ng PDGF-BB, 200 ng IGF-I alone or in combination in the buccal submucosal area of the orthodontic tooth. The injection was applied every other day. The experiment continued for ten days and then the rats were sacrificed. The expression of integrin (beta3 protein in periodontal ligament tissues of the compressing side was detected by immunohistochemical techniques. RESULTS: The expression of integrin (beta3 protein in periodontal ligament tissues of the compressing side of each experimental group was significantly increased compared with that of the control group (P<0.01). Meanwhile the maximum mean optical density value of integrin (beta3 protein expression was attained in the combination group which showed a significant increase compared with the PDGF-BB group (P<0.05) and the IGF-I group (P<0.01). CONCLUSION: The combination of exogenous PDGF-BB and IGF- I in orthodontic tooth movement may enhance the expression of integrin (beta3 protein in periodontal ligament cells and PDGF-BB and IGF-I may have a synergistic effect during orthodontic tooth movement.