Correlation between IFNAR1 expression in peripheral blood T lymphocytes and inflammatory cytokines, tumor-infiltrating lymphocytes, and chemosensitivity in patients with colorectal cancer.

IFN-α receptor (IFNAR) is critical for maintaining the crosstalk between cancer cells and lymphocytes. We investigated IFNAR1 expression in peripheral blood CD4+ and CD8+ T cells and explored their relationships with plasma cytokines, chemosensitivity and infiltrated T cells in the tumor microenvironment (TME) of colorectal cancer (CRC). The levels of IFNAR1, IFN-γ, and PD1 in peripheral T cells were tested using flow cytometry. Immunohistochemical staining of IFNAR1 in CRC tissues was performed. A cytometric bead array was used to determine the plasma concentrations of cytokines. In CRC patients, IFNAR1 levels were significantly increased in peripheral blood T cells, and plasma IL-6 levels were also significantly increased. Pearson correlation analysis revealed that IFNAR1 expression in CD8+ T cells was negatively associated with plasma IL-2, IFN-γ, and TNFα. IFNAR1 expression in CD4+ T cells was positively associated with TME infiltrated levels of CD8+ T cells. The levels of CD8+ T cells with IFNAR1 and plasma IFN-γ were associated with chemosensitivity. Collectively, IFNAR1 levels in CD4+ and CD8+ T cells were significantly upregulated in CRC patients and positively associated with T-cell infiltration. IFNAR1 may be a chemotherapy biomarker for predicting response.

Computed tomographic parameters correlate with coagulation disorders in isolated traumatic brain injury.

BACKGROUND AND OBJECTIVE: The imbalanced hemostatic equilibrium caused by brain tissue or vessel damage underlies the pathophysiology of traumatic brain injury (TBI)-induced coagulopathy, and cranial computed tomography (CT) is the gold standard for evaluating brain injury. The present study aimed to explore the correlation between quantitative cranial CT parameters and coagulopathy after TBI. METHODS: We retrospectively collected the medical records of TBI patients with extracranial abbreviated injury scale (AIS) scores <3 who were admitted to our institution. The quantitative cranial CT parameters of patients with and without coagulopathy were compared, and univariate correlation analysis between CT parameters and coagulation subtest values and platelet counts was performed. The predictors for each subtest of coagulation function were probed by multivariate regression. RESULTS: TBI patients with coagulopathy had a larger intracerebral haematoma/contusion (ICH/C) volume (p < 0.001), a higher incidence of compressed basal cisterns (p = 0.015), a higher Graeb score (p < 0.001) and subarachnoid haematoma (Fisher's scaling score) (p = 0.019) than those without coagulopathy. IH/C volume was identified as an independent risk factor for predicting coagulopathy. ICH/C volume showed a significantly positive correlation with APTT (Pearson's correlation = 0.333, p < 0.001), while a significant negative correlation with PLT (Pearson's correlation = - 0.312, p < 0.001). CONCLUSION: ICH/C volume was a main quantitative cranial CT parameter for predicting coagulopathy, suggesting that parenchymal brain damage and vessel injury were closely associated with coagulopathy after TBI.

Long-term outcomes after extra-levator versus conventional abdominoperineal excision for low rectal cancer.

PURPOSE: Extralevator (ELAPE) and abdominoperineal excision (APE) are two major surgical approaches for low rectal cancer patients. Although excellent short-term efficacy is achieved in patients undergoing ELAPE, the long-term benefits have not been established. In this study we evaluated the safety, pathological and survival outcomes in rectal cancer patients who underwent ELAPE and APE. METHODS: One hundred fourteen patients were enrolled, including 68 in the ELAPE group and 46 in the APE group at the Beijing Chaoyang Hospital, Capital Medical University from January 2011 to November 2020. The baseline characteristics, overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS) were calculated and compared between the two groups. RESULTS: Demographics and tumor stage were comparable between the two groups. The 5-year PFS (67.2% versus 38.6%, log-rank P = 0.008) were significantly improved in the ELAPE group compared to the APE group, and the survival advantage was especially reflected in patients with pT3 tumors, positive lymph nodes or even those who have not received neoadjuvant chemoradiotherapy. Multivariate analysis showed that APE was an independent risk factor for OS (hazard ratio 3.000, 95% confidence interval 1.171 to 4.970, P = 0.004) and PFS (hazard ratio 2.730, 95% confidence interval 1.506 to 4.984, P = 0.001). CONCLUSION:  Compared with APE, ELAPE improved long-term outcomes for low rectal cancer patients, especially among patients with pT3 tumors, positive lymph nodes or those without neoadjuvant chemoradiotherapy.

Long-Term Outcomes of Ligation of the Inter-Sphincteric Fistula Tract Plus Bioprosthetic Anal Fistula Plug (LIFT-Plug) in the Treatment of Trans-Sphincteric Perianal Fistula.

BACKGROUND The ligation of the inter-sphincteric fistula tract plus bioprosthetic anal fistula plug (LIFT-plug) is a new procedure in the treatment of trans-sphincteric perianal fistulas. The aim of this study was to evaluate its long-term outcomes. MATERIAL AND METHODS Clinical data of 78 patients with trans-sphincteric perianal fistula who were managed by the LIFT-plug technique between March 2014 to October 2016 were analyzed retrospectively. The operation time, healing rate, postoperative complications, recurrences, and length of stay were reviewed. RESULTS No serious complications occurred during the operation in all patients. The median follow-up was 30 months (16 to 47 months), clinical healing of the anal fistula occurred in 75 patients (96.2%). The median operative time was 25 minutes (18 to 45 minutes). The mean complete healing time was 16 days (9 to 46 days). The median healing time for the external anal fistula opening was 2 weeks (range, 2 to 3 weeks), and the inter-sphincteric groove incision healing time was 4 weeks (range, 3 to 7 weeks). The median hospital stay after operation was 5 days. Fistula recurred in 2 patients because of spontaneous expulsion of the plug at 7 days post-surgery; perianal abscess occurred in 1 patient. The anal function was evaluated in 70 patients of the 78 patients. Perfect control of continence was recorded for 97.1% of the patients (68 out of 70 patients). Two patients were identified to a rare complication of gas incontinence (Wexner score 1). CONCLUSIONS LIFT-plug procedure for the treatment of trans-sphincteric fistulas is a simple procedure with a high healing rate, minimal invasiveness, quick healing, and without disturbance to anal function. LIFT-plug is an ideal procedure for trans-sphincteric fistula.

Selective precipitation and characterization of lignin-carbohydrate complexes (LCCs) from Eucalyptus.

MAIN CONCLUSION: Six types of lignin-carbohydrate complex (LCC) fractions were isolated from Eucalyptus. The acidic dioxane treatment applied significantly improved the yield of LCCs. The extraction conditions had a limited impact on the LCC structures and linkages. Characterization of the lignin-carbohydrate complex (LCC) structures and linkages promises to offer insight on plant cell wall chemistry. In this case, Eucalyptus LCCs were extracted by aqueous dioxane, and then precipitated sequentially by 70% ethanol, 100% ethanol, and acidic water (pH = 2). The composition and structure of the six LCC fractions obtained by selective precipitation were investigated by sugar analysis, molecular weight determination, and 2D HSQC NMR. It was found that the acidic (0.05-M HCl) dioxane treatment significantly improved the yield of LCCs (66.4% based on Klason lignin), which was higher than the neutral aqueous dioxane extraction, and the extraction condition showed limited impact on the LCC structures and linkages. In the fractionation process, the low-molecular-weight LCCs containing a high content of carbohydrates (60.3-63.2%) were first precipitated by 70% ethanol from the extractable solution. The phenyl glycoside (PhGlc) bonds (13.0-17.0 per 100Ar) and highly acetylated xylans were observed in the fractions recovered by the precipitation with 100% ethanol. On the other hand, such xylan-rich LCCs exhibited the highest frequency of ß-O-4 linkages. The benzyl ether (BE) bonds were only detected in the fractions obtained by acidic water precipitation.

Percutaneous radiologic gastrostomy via nasopharyngeal intubation for the treatment of patients with complete malignant pharyngoesophageal obstruction.

BACKGROUND/AIMS: For patients with complete malignant pharyngoesophageal obstruction (CMPO), percutaneous radiologic gastrostomy (PRG) under ultrasound/CT guidance can complicate it to cause failure due to unsatisfied stomach filling. In this study, we retrospectively investigated whether PRG via nasopharyngeal intubation is feasible and effective for these patients. METHODOLOGY: PRG via nasopharyngeal intubation was attempted in 21 patients with CMPO (mean 70.8 ± 8.23 years). The technique comprised a dilation of the stomach via nasopharyngeal intubation using a catheter, followed by fluoroscopically guided puncture and gastrostomy tube placement. Complications including hemorrhage, peritonitis, gastrojejunocolic fistula, infection of puncture site, tube blocking and outleakage was observed during and after the procedure. RESULTS: A 5F catheter was successfully inserted to the stomach under fluoroscopical guidance and subsequent PRG was performed in all 21 patients. Minor complications occurred in 14.3% patients including mild infection of the fistula in 1, tube blocking in 1 and unexpected tube drawing out in 1. Follow-up nutrition indexes revealed obvious improved nutrition compared to before PRG (P < 0.05). CONCLUSION: PRG via nasopharyngeal intubation was simple, feasible and effective for patients with CMPO.

[Risk factors associated with incisional surgical site infection in colorectal cancer surgery with primary anastomosis].

OBJECTIVE: To investigate the incidence of surgical site infection (SSI) and risk factors in colorectal cancer surgery patients. METHODS: Between October 2003 and October 2013, 1 381 consecutive patients with colorectal cancer managed surgically with primary anastomosis were included in the study. There were 762 male and 619 female patients with mean body mass index (BMI) was (27.7 ± 3.7) kg/m², aged from 20 to 90 years with a median of 67 years. Patients undergoing emergency surgery and requiring stoma creation were excluded. The patients' characteristics, surgical conditions and prognosis were recorded. Univariate and multiple logistic regression analysis were used to identify any variable predictive factors of SSI. RESULTS: One hundred twenty-six (9.12%) cases developed incisional SSI. The occurrence time for SSI was from 2 to 20 days, mean (6.7 ± 2.9) days. According to multivariable logistic regression analysis, BMI (OR = 1.058, P = 0.030), intraoperative contamination (OR = 10.549, P = 0.000) and open operation as compared with a laparoscopic procedure (OR = 2.111, P = 0.001) were significant independent predictors of incisional SSI. There was a significant decrease in incisional SSI in wound protectors group (OR = 1.646, P = 0.012). CONCLUSION: BMI and intraoperative contamination are independent predictors of incisional SSI, and wound protectors and laparoscopic surgery are associated with a lower incidence of incisional SSI following colorectal cancer surgery.

FNDC5 prevents oxidative stress and neuronal apoptosis after traumatic brain injury through SIRT3-dependent regulation of mitochondrial quality control.

Mitochondrial dysfunction and oxidative stress are important mechanisms for secondary injury after traumatic brain injury (TBI), which result in progressive pathophysiological exacerbation. Although the Fibronectin type III domain-containing 5 (FNDC5) was reported to repress oxidative stress by retaining mitochondrial biogenesis and dynamics, its possible role in the secondary injury after TBI remain obscure. In present study, we observed that the level of serum irisin (the cleavage product of FNDC5) significantly correlated with the neurological outcomes of TBI patients. Knockout of FNDC5 increased the lesion volume and exacerbated apoptosis and neurological deficits after TBI in mice, while FNDC5 overexpression yielded a neuroprotective effect. Moreover, FNDC5 deficiency disrupted mitochondrial dynamics and function. Activation of Sirtuin 3 (SIRT3) alleviated FNDC5 deficiency-induced disruption of mitochondrial dynamics and bioenergetics. In neuron-specific SIRT3 knockout mice, FNDC5 failed to attenuate TBI-induced mitochondrial damage and brain injuries. Mechanically, FNDC5 deficiency led to reduced SIRT3 expression via enhanced ubiquitin degradation of transcription factor Nuclear factor erythroid 2-related factor 2 (NRF2), which contributed to the hyperacetylation and inactivation of key regulatory proteins of mitochondrial dynamics and function, including OPA1 and SOD2. Finally, engineered RVG29-conjugated nanoparticles were generated to selectively and efficiently deliver irisin to the brain of mice, which yielded a satisfactory curative effect against TBI. In conclusion, FNDC5/irisin exerts a protective role against acute brain injury by promoting SIRT3-dependent mitochondrial quality control and thus represents a potential target for neuroprotection after TBI.

A nomogram to predict intracranial hypertension in moderate traumatic brain injury patients.

OBJECTIVE: Patients with moderate traumatic brain injury (TBI) are under the threat of intracranial hypertension (IHT). However, it is unclear which moderate TBI patient will develop IHT and should receive intracranial pressure (ICP)-lowering treatment or invasive ICP monitoring after admission. The purpose of the present study was to develop and validate a prediction model that estimates the risk of IHT in moderate TBI patients. METHODS: Baseline data collected on admission of 296 moderate TBI patients with Glasgow Coma Scale (GCS) score of 9-11 was collected and analyzed. Multi-variable logistic regression modeling with backward stepwise elimination was used to develop a prediction model for IHT. The discrimination efficacy, calibration efficacy, and clinical utility of the prediction model were evaluated. Finally, the prediction model was validated in a separate cohort of 122 patients from 3 hospitals. RESULTS: Four independent prognostic factors for IHT were identified: GCS score, Marshall head computed tomography score, injury severity score and location of contusion. The C-statistic of the prediction model in internal validation was 84.30% (95% confidence interval [CI]: 0.794-0.892). The area under the curve for the prediction model in external validation was 82.80% (95% CI: 0.747∼0.909). CONCLUSIONS: A prediction model based on baseline parameters was found to be highly sensitive in distinguishing moderate TBI patients with GCS score of 9-11 who would suffer IHT. The high discriminative ability of the prediction model supports its use in identifying moderate TBI patients with GCS score of 9-11 who need ICP-lowering therapy or invasive ICP monitoring.

[Surgical management of postoperative stricture of anastomosis after operation of intersphincteric resection for lower rectal cancer].

OBJECTIVE: To study surgical treatment of postoperative stricture of anastomosis for lower rectal cancer. METHODS: The data of 9 cases who were diagnosed as postoperative stricture of anastomosis after operation of intersphincteric resection for lower rectal cancer during January 2008 to June 2011 were analyzed retrospectively. Transanal excision of stricture were used in 3 cases diagnosed as membranous stricture. Transanal radial incision of stricture were used in 5 cases diagnosed as tubulous stricture. Biologic patch was used to repair the defect of the posterior wall of rectum after excision of severe stricture in 1 case. RESULTS: All 9 cases of postoperative stricture of anastomosis were cured by surgery. Anal dilation were performed every day by patients themselves after discharge. Digital examination showed that 1 to 2 fingers could pass through the anastomosis after operation. The patient whose rectal defect was repaired by biological patch underwent colonoscopy examination two weeks after operation. Colonoscopy showed that the biological patch had been filled with granulation and integrated into the surrounding intestinal tissue. All patients defecated without difficulty and the anal function of all patients was good after restoration of intestinal continuity. CONCLUSION: Aggressive surgery, combining with the use of biological patch if necessary is an effective therapy of postoperative stricture of anastomosis for lower rectal cancer.

[Technical improvements and results of individual cylindrical abdominoperineal resection for locally advanced low rectal cancer].

OBJECTIVE: To evaluate the safety and efficacy of individual cylindrical abdominoperineal resection (CAPR) for locally advanced low rectal cancer. METHODS: From June 2011 to February 2012, 11 patients with locally advanced low rectal cancer underwent individual CAPR. There were 7 male and 4 female patients, aged from 32 to 74 years with a median of 64 years. Forty-seven patients underwent classic CAPR from January 2008 to February 2012. Preoperative and postoperative parameters such as clinical information of patients, tissue morphometry and complications were compared. RESULTS: In the individual surgical group, 6 patients were treated with one side levator ani muscle totally or partially reserved, 3 patients with sacrococcyx reserved, and 2 patients with dissection close to the anterior rectal wall. Compared with classical surgery, the individual surgical specimens of horizontal section area ((2197 ± 501) mm(2)) and intrinsic muscle layer outer area ((1722 ± 414) mm(2)) were small, but the difference was not statistically significant (P = 0.150 and 0.167). The operative time, intraoperative blood loss, circumferential resection margin, total cross sectional tissue area, cross sectional tissue area outside the muscularis propria and bowel perforation rate between the two groups were not significantly different. Individual CAPR showed less incidence of chronic perineal pain (2/11, χ(2) = 6.116, P = 0.013) and sexual dysfunction (2/9, χ(2) = 4.412, P = 0.036) compared with classic CAPR. CONCLUSIONS: Individual CAPR has the potential to reduce the risk of chronic perineal pain and sexual dysfunction without influencing the radical effect when compare with classic CAPR for the treatment of low rectal cancer.

Multimodality Therapy, Followed by Laparoscopic Gastrectomy, for Unresectable Gastric Cancer With Outlet Obstruction and Bulky N2 Metastases.

BACKGROUND: Patients who have gastric cancer with outlet obstruction (GCOO) and bulky N2 metastases cannot undergo curative resection and tolerate chemotherapy poorly, which may be improved by multimodality therapy (MMT) combined with laparoscopic gastrectomy. PATIENTS AND METHODS: The records of patients with GCOO and bulky N2 metastases who received MMT including nasojejunal feeding combined with preoperative chemotherapy (PCT), followed by laparoscopic exploration [enteral nutritional (EN) group] in sequence or laparoscopic gastrojejunostomy (LGJ) before PCT plus laparoscopic gastrectomy (LGJ group) were retrospectively reviewed. Prognostic Nutritional Index, gastric outlet obstruction scoring system grade, quality of life, response to PCT, surgical outcomes, and long-term survival were analyzed. RESULTS: Fifty-four consecutive patients with GCOO and bulky N2 metastases were identified. The Prognostic Nutritional Index and Nutritional Risk Screening-2002 score of patients were significantly improved as a result of multimodal therapy, but no superiority was demonstrated between the EN group and the LGJ group. The quality of life (52.6 ± 11.4 vs 68.2 ± 13.5, P = 0.036) and gastric outlet obstruction scoring system (P < 0.05) of patients in the LGJ group were better compared with the EN group. The rate of laparoscopic D2 gastrectomy (94.3% vs 92.9%, P = 0.64) and R0 resection (91.4% vs 92.9%, P = 0.53) in the EN group was similar to the LGJ group. There were no significant differences for the 5-year overall survival rate (63.2% vs 57.1, P = 0.86) and the 5-year relapse-free survival rate (42.9% vs 53.8%, P = 0.54) of patients in the EN group compared with the LGJ group. CONCLUSIONS: MMT including EN support or laparoscopic gastrojejunostomy followed by laparoscopic D2 gastrectomy is a feasible and effective treatment for patients with GCOO and bulky N2 metastases.

Development and validation of a nomogram predictive model for colorectal adenoma with low-grade intraepithelial neoplasia using routine laboratory tests: A single-center case-control study in China.

Background: Colorectal cancer (CRC) is the third most common cancer in the world and has a high mortality rate. Colorectal adenoma (CRA) is precancerous lesions of CRC. The purpose of the present study was to construct a nomogram predictive model for CRA with low-grade intraepithelial neoplasia (LGIN) in order to identify high-risk individuals, facilitating early diagnosis and treatment, and ultimately reducing the incidence of CRC. Methods: We conducted a single-center case-control study. Based on the results of colonoscopy and pathology, 320 participants were divided into the CRA group and the control group, the demographic and laboratory test data were collected. A development cohort (n = 223) was used for identifying the risk factors for CRA with LGIN and to develop a predictive model, followed by an internal validation. An independent validation cohort (n = 97) was used for external validation. Receiver operating characteristic curve, calibration plot and decision curve analysis were used to evaluate discrimination ability, accuracy and clinical practicability of the model. Results: Four predictors, namely sex, age, albumin and monocyte count, were included in the predictive model. In the development cohort, internal validation and external validation cohort, the area under the curve (AUC) of this risk predictive model were 0.946 (95%CI: 0.919-0.973), 0.909 (95 % CI: 0.869-0.940) and 0.928 (95%CI: 0.876-0.980), respectively, which demonstrated the model had a good discrimination ability. The calibration plots showed a good agreement and the decision curve analysis (DCA) suggested the predictive model had a high clinical net benefit. Conclusion: The nomogram model exhibited good performance in predicting CRA with LGIN, which can aid in the early detection of high-risk patients, improve early treatment, and ultimately reduce the incidence of CRC.

TNF-α expression in the UCB-MSCs as stable source inhibits gastric cancers growth in nude mice.

Mesenchymal stem cells (MSCs) are potentially vehicles for therapy of malignant diseases. In our study, we investigated whether UCB-MSCs are capable to carry TNF-α to target tumor cells in vivo. The human gastric cancer cells SGC-7901 were subcutaneously injected into the abdomen near groins of 15 nude mice to establish experiment tumor models. MSC-TNF-α demonstrated a strong suppressive effect on the tumor growth compared with MSC and NaCl. Thus, MSC-TNF-α can obviously inhibit Gastric cancers growth in nude mice, indicating that UCB-MSCs may have the potential to become a prevention approach against gastric cancer.

[Value of self-expanding metallic stent for obstructing left-sided colon cancer or rectal cancer].

OBJECTIVE: To investigate the therapeutic value of self-expanding metallic stent (SEMS) for resectable obstructing left-sided colon cancer or rectal cancer. METHODS: Clinical data of 73 patients who had acute obstruction due to left-sided colon cancer or rectal cancer during May 2007 to January 2012 were retrospectively analyzed. The patients were divided into 2 groups: SEMS group (34 cases) underwent surgical resection after insertion of SEMS; emergency surgery group (39 cases) underwent emergency operation. The 2 group patients were compared for the incidence of primary anastomosis, stoma rate, laparoscopic surgery rate, mortality, postoperative morbidity, ICU admission rate, length of ICU stay, hospital stay, and hospitalization costs. RESULTS: The incidence of primary anastomosis in SEMS group was significantly higher than that in emergency surgery group (97.1% vs. 56.4%, χ(2) = 16.256, P < 0.001), and the protective stoma rate and permanent stoma rate in SEMS group were both lower than those in emergency surgery group (33.3% vs. 86.3%, 2.9% vs. 43.6%, χ(2) value were 14.972 and 16.156, both P < 0.001). Patients in SEMS group underwent significantly more laparoscopic surgery than in emergency surgery group (47.1% vs. 0, χ(2) = 23.505, P < 0.001). There were no significant difference in postoperative mortality (2.9% vs. 10.3%, P = 0.364). The postoperative morbidity in SEMS group was significantly lower than that in emergency surgery group (35.3% vs. 66.7%, P = 0.007). Incisional infection was the most common complication in both groups, and the incidence of which seemed to be more higher in emergency surgery group (17.6% vs. 38.5%, χ(2) = 3.840, P = 0.050). There was a lower ICU admission rate in SEMS group (24.2% vs. 53.9%, χ(2) = 6.972, P = 0.008), and the mean length of ICU stay and hospital stay were both shorter in SEMS group ((69.5 ± 7.4) hours vs. (114.3 ± 10.9) hours, t = -20.23, P < 0.001; (19.6 ± 4.8) days vs. (23.4 ± 6.2) days, t = -2.90, P = 0.005). The cost of hospitalization was less in SEMS group (45 383 ± 15 648 vs. 61 485 ± 20 380, t = -3.74, P < 0.001). CONCLUSIONS: SEMS can effectively relieve the large intestinal obstruction caused by left-sided colon cancer or rectal cancer, and change the traditional emergency surgery into a selective surgery with better outcomes. SEMS appears to be a valuable technique for resectable obstructing left-sided colorectal cancer.

Comparison of three different treatment methods for traumatic and Iatrogenic peripheral artery pseudoaneurysms.

OBJECTIVE: To compare the efficacy of open surgery (OS), endovascular interventions (EIs), and ultrasound-guided thrombin injection (UGTI) for the treatment of peripheral arterial pseudoaneurysms (PAs). METHODS: From January 1, 2001, to February 10, 2021, 38 patients diagnosed with traumatic and iatrogenic PAs treated with OS, EI, and UGTI were retrospectively analyzed. There were 18 females and 20 males, with an age of 56.47 ± 14.08 years (range,17-87 years). Anesthesia modality, operation duration, blood transfusion, duration of hospital stay, primary and secondary success rates, and complication rate were used to evaluate the surgical outcomes. RESULTS: There were 11 cases under regional anesthesia and 4 under general anesthesia in OS group, 9 under regional anesthesia and 1 under general anesthesia in EI group, and no regional or general anesthesia was required in UGTI group. There was no significant differences between any two groups (χ2  = 39.80, p < 0.05). The blood tranfusion amount (units) were 3.6 ± 6.0, 0.8 ± 2.5, 0.0 ± 0.0 for OS, EI, and UGTI groups, respectively, with significant difference between OS and UGTI groups (F = 3.03, p < 0.05). The operation duration (minutes) of OS, EI, and UGTI groups were 80.0 ± 41.9, 56.0 ± 8.4, and 22.7 ± 5.3, respectively, with significant difference between any two groups (F = 15.69, p < 0.05). The duration of hospital stay (days) were 47.7 ± 39.0, 31.5 ± 17.6, and 16.3 ± 9.5, repectively, with significant difference between any two groups (F = 47.73, p < 0.05). The primary clinical success rates were 80% (12/15), 90% (9/10), and 92.3% (12/13) in OS,EI, and UGTI groups, respectively, with no significant difference between any two groups (χ2  = 0.34, p > 0.05). The secondary clinical success rates were 100% for all three groups. The overall complication rates of OS, EI, and UGTI groups were 20% (3/15), 10% (1/10), and 7.7% (1/13), respectively, with no significant difference between any two groups (χ2  = 1.00, p > 0.05). The infection rates were 13.3% (2/15), 10% (1/10), and 0% (0/13) in OS, EI, and UGTI groups respectively, with no significant difference between any two groups (χ2  = 1.80, p > 0.05). The reintervention rates were 6.7% (1/15), 0% (0/10), 7.7% (1/13) in OS, EI, and UGTI groups, respectively, with no significant difference between two groups (χ2  = 0.95, p > 0.05). Neuralgia was relieved in all patients. CONCLUSIONS: OS, EI, and UGTI are efficacious and safe options for the treatment of appropriate patients with traumatic and iatrogenic PAs. UGTI would be considered as a first-line therapy for this condotion.

The Efficacy of Combined Therapy of Regorafenib with Detoxicating and Stasis Softening Chinese Herbal Spleen Tonics in Mid-/Late-Stage Hepatocellular Carcinoma.

Objective: To explore the efficacy of combined therapy of Regorafenib with detoxicating and stasis softening Chinese herbal spleen tonics (DSS-splenic tonics) in mid-/late-stage hepatocellular carcinoma. Methods: Retrospective observational data of 120 patients were obtained, 60 of which received combined therapy of DSS-splenic tonics and regorafenib. Adverse event, overall survival (OS), and time-to-progress (TTP) were analyzed. Synergistic effect of DSS-spleen tonics was found and validated in human hepatocellular carcinoma HCCLM3 cell line and xenograft mouse models. Results: Combination of regorafenib and DSS-splenic tonics also slightly extended the TTP and OS compared with treatment of regorafenib alone, suggesting DSS-splenic tonics has synergistic effect with regorafenib. Both Regorafenib and DSS-spleen tonics exerted inhibitory effect on cell viability and invasion capability of HCCLM3 cells, and combining both could enhance the antitumor effect. At molecular level, we found that VEGF, HIF-1α, MVD, and VEGF2 were all suppressed by regorafenib and DSS-splenic tonics. These results suggest that DSS-spleen tonics function synergistically with regorafenib in HCC by enhancing the regulation of regorafenib on VEGF, MMP-2, HIF-1α, and MVD, and may diminish angiogenesis during HCC progression. Conclusion: DSS-spleen tonics could exert synergistic antitumor effect with regorafenib via targeting VEGF.

Long-Read Nanopore Sequencing Identifies Mismatch Repair-Deficient Related Genes with Alternative Splicing in Colorectal Cancer.

Background: Alternative splicing (AS) plays a crucial role in regulating the progression of colorectal cancer (CRC), but its distribution remains to be explored. Here, we aim to investigate the genes edited by AS which show differential expression in patients with mismatch repair deficiency (dMMR)/microsatellite instability (MSI). Materials and Methods: We applied long-read nanopore sequencing to determine the mRNA profiles and screen AS genes using Oxford Nanopore Technologies (ONT) method in ten paired CRC tissues. CRC tissue and plasma samples were used to validate the differential genes with AS using real-time fluorescent quantitative PCR, immunohistochemistry, and enzyme-linked immunosorbent assay. Results: ONT sequencing identified 404 genes were downregulated, and 348 genes were upregulated in MSI cancer tissues compared with microsatellite stability (MSS) cancer tissues. In total, 6,200 AS events were identified in 2,728 mRNA transcripts. WGCNA revealed dMMR/MSI-correlated gene modules, including INHBA and RPL22L1, which were upregulated; conversely, HMGCS2 was downregulated in MSI cancer. Overexpression of RPL22L1, INHBA, and CAPZA1 was further confirmed in CRC tissues. INHBA was found to be associated with tumor lymphatic metastasis. Importantly, the levels of INHBA in CRC plasma were significantly increased compared with those in noncancer plasma. INHBA showed a higher level in dMMR/MSI CRC than in MSS CRC, indicating that INHBA is a useful biomarker. Conclusion: Our results showed that ONT-identified genes provide a pool to explore AS-associated markers for dMMR/MSI CRC. We demonstrated INHBA as a promising signature for clinical application in predicting tumor lymphatic metastasis and screening dMMR/MSI candidates.

Predictors of long-term survival in large gastric carcinoma patients.

BACKGROUND/AIMS: To improve the treatment results for large gastric carcinoma, it is important to know the characteristics of long-term survivors. The aim of this study was to analyze the clinicopathological features of large gastric carcinoma patients and clarify the prognostic factors associated with long-term survival. METHODOLOGY: Between December 1996 and December 2002, a total of 334 patients entered the study. They underwent surgery for gastric carcinomas measuring 10cm or more in diameter. We examined 12 clinicopathological factors associated with the patient, tumor and surgery. Multivariate analysis was performed using Cox's proportional hazards model. RESULTS: The 5-year survival rate was influenced by the extent of lymph node dissection, histological type, depth on invasion, lymph node metastasis, peritoneal dissemination, liver metastasis and disease stage. Of these, two independent prognostic factors were depth on invasion and lymph node metastasis. CONCLUSIONS: Depth on invasion and lymph node metastasis emerged as two independent prognostic factors for the prediction of long-term survival in large gastric carcinoma patients. We can make a suitable treatment strategy for patients with gastric cancer through consideration of the prognostic factors.

Horizontal Rafting Plate for Treatment of the Tibial Plateau Fracture.

OBJECTIVE: This study aimed to investigate the value of a horizontal rafting plate in treating tibial plateau fractures. METHODS: The data of 24 patients in whom a horizontal rafting plate was used to treat a tibial plateau fracture between October 2014 and January 2018 were retrospectively analyzed, including 16 males and 8 females, aged 21-63 years old, with an average of 40 ± 14.68 years. The fractures included 13 in the left knee and 11 in the right knee. The places where the horizontal rafting plate were used included the anterior margin of tibia, anterolateral tibia, and posterolateral tibia. All cases were followed up for 12-24 months, with an average follow-up of 17.5 ± 5.0 months. At the last follow-up, the Rasmussen radiological criteria were used to evaluate the effect of fracture reduction and fixation. The knee joint function was evaluated using the Rasmussen functional score. Computed tomography (CT) scanning and three-dimensional reconstruction were performed preoperatively and postoperatively, with the quality of reduction of the fractured articular surface clarified by the final follow-up. The flexion and extension abilities of the knee joint were also measured in the postoperative follow-up. RESULTS: Preoperative CT scanning showed that the gap of the tibial plateau was 8.00 ± 1.40 (5-24) mm. The heights of the fracture of the articular surface at all three sites during the final follow-ups were significantly different from the height before the surgery (P < 0.05). The vertical distance between the articular line and the highest point of the articular surface after reduction was 0.17 ± 0.05 mm. Anatomic reductions were obtained in 24 patients. The Rasmussen functional score after surgeries was 27.25 ± 0.94 points. Bony union was achieved in all the patients. According to the Rasmussen radiological criteria, the scores during the last follow-up were as follows: the total score was 13-18 points, with an average of 16.00 ± 1.72 points; the scores were excellent in 17 cases and good in seven cases. Therefore, 100% of results were excellent or good. No infection or fracture nonunion was found. CONCLUSION: Using a horizontal plate can be an effective method for treating special types of fractures of the tibial plateau, including the anterior margin and anterolateral and posterolateral tibial plateau, with satisfactory treatment efficacy.