Tumor-infiltrating CD226+CD8+ T cells are associated with postoperative prognosis and adjuvant chemotherapeutic benefits in gastric cancer patients.

PURPOSE: Defining the phenotypic characteristics of CD8+ T cell subsets in gastric cancer (GC) can help remodel the immune microenvironment of the tumor, thereby improving patient prognosis. CD226 has recently been shown to regulate the activity of CD8+ T cell in several malignancies. However, the clinical relevance of CD226+CD8+ T cells in GC remains unclear. METHODS: Fudan University Shanghai Cancer Center (FUSCC) cohort (n = 316), The Cancer Genome Atlas (TCGA) cohort (n = 407), KUGH/KUCM cohort (n = 202), and Asian Cancer Research Group (ACRG) cohort (n = 300) were included in prognosis and response to adjuvant chemotherapy (ACT) analyses. Flow cytometry and multiplex immunostaining were used to characterize CD226+CD8+ T cells. RESULTS: CD226+CD8+ T cells predicted favorable outcomes in patients undergoing curative resection for GC. GC patients with high CD226+CD8+ T cell infiltration benefitted more from adjuvant chemotherapy. CD155 is upregulated in GC tissues and is associated with decreased intra-tumoral CD226+CD8+ T cell infiltration. The combination of intra-tumoral CD226+CD8+ T cells and CD155 is a strong prognostic predictor in patients with GC. CONCLUSION: CD226+CD8+ T cells may represent a novel therapeutic target and a useful marker of prognosis and therapeutic response in patients with GC.

Apatinib combined with PD-L1 blockade synergistically enhances antitumor immune responses and promotes HEV formation in gastric cancer.

PURPOSE: Apatinib, an antiangiogenic drug, has shown beneficial effects only in a fraction of advanced gastric cancer (GC) patients. Given the recent success of immunotherapies, combination of apatinib with immune checkpoint inhibitor may provide sustained and potent antitumor responses. METHODS: Immunocompetent mice with subcutaneous MFC tumors grown were given a combination of apatinib and anti-PD-L1 antibody therapy. GC tissues from patients undergoing curative resection in China were collected, and the density of HEVs, MSI status and tumor-infiltrated lymphocytes were analyzed by immunohistochemical staining. RESULTS: Combined apatinib and PD-L1 blockade therapy synergistically delayed tumor growth and increased survival in MFC-bearing immunocompetent mice. The combination therapy promoted antitumor immunity by increasing the ratio of CD8+ cytotoxic T cells to Foxp3+ Treg cells, the accumulation of CD20+ B cells and the Th1/Th2 cytokine ratio (IFN-γ/IL-10). The combination therapy induced the formation of HEVs through activation of LTßR signaling, thus promoting CD8+ cytotoxic T cell and CD20+ B cell infiltration in tumors. In clinical GC samples, the density of HEVs positively correlated with the intratumoral infiltration of CD8+ cytotoxic T cells and CD20+ B cells. MSI-high GC showed a higher density of HEVs, CD8+ cytotoxic T cells and CD20+ B cells than MSS/MSI-low GC. GC patients with high densities of HEVs, CD8+ cytotoxic T cells and CD20+ B cells had an improved prognosis with superior overall survival. CONCLUSION: Combining apatinib with PD-L1 blockade treatment synergistically enhances antitumor immune responses and promotes HEV formation in GC.

New treatment of patellar instability after total knee arthroplasty: A case report and review of literature.

BACKGROUND: Patellar instability is an uncommon complication after total knee arthroplasty (TKA). Partial lateral patella facetectomy (LPF) with lateral retinaculum release treatment of patellar instability is rarely reported. CASE SUMMARY: We present a case of patellar instability 8 mo after primary TKA. Treatment of this complication was adapted to address the cause of the dislocation. To eliminate patellar instability, we restored the vastus medialis and performed LPF with lateral retinaculum release. We achieved normal patellar tracking. Clinical and radiographic evaluations at the 1-year postoperative follow-up were satisfactory. CONCLUSION: LPF with lateral retinaculum release represents a promising option to restore central patellar tracking in patients with patellar instability after TKA in cases without component malposition.

Effects of Short-Term Low-Dose Glucocorticoids for Patients with Mild COVID-19.

OBJECTIVES: To evaluate the role of short-term low-dose glucocorticoids in mild COVID-19 patients. METHODS: We conducted a retrospective, cross-sectional, single-center study in Kunming, China. A total of 33 mild COVID-19 cases were divided into two treatment groups (with and without glucocorticoids, methylprednisolone, were used in this setting), and the absolute value of peripheral blood lymphocyte count; CD3+, CD4+, and CD8+ T cell counts; and the time to achieve negative transformation of a nucleic acid pharyngeal swab were recorded. Peripheral blood lymphocyte and T cell counts were compared between the treatment group and 25 healthy individuals. At the point of time when there was a 50% accumulation conversion rate (positive to negative nucleic acid on pharyngeal swab), and the nucleic acid turned negative in half of the patients in two groups, the peripheral blood lymphocyte and T cell counts were compared between treatment groups. RESULTS: The mean cumulative time for the 50% negative conversion rate of the nucleic acid in the pharyngeal swab was 17.7 ± 5.1 days and 13.9 ± 5.4 days in the glucocorticoid group and the nonglucocorticoid group, respectively. The absolute peripheral blood lymphocyte count and the T cell subset count in the glucocorticoid group were lower than those in the nonglucocorticoid group. When the nucleic acid turned negative in half of the patients, the absolute value of peripheral blood lymphocyte count and CD4+ T cells of the glucocorticoid group and the nonglucocorticoid group was not significantly different; the CD3+ and CD8+ T cells in the glucocorticoid group were lower than those in the nonglucocorticoid group. The absolute peripheral blood lymphocyte count, CD3+ T cells, and CD4+ T cells in the glucocorticoid group were lower than those of the healthy group during the whole disease period, and CD8+ T cells returned to normal at 19-21 days of the disease period. There was no significant difference between the nonglucocorticoid group and the healthy group for absolute peripheral blood lymphocyte and CD8+ T cells; moreover, CD3+ T cells and CD4+ T cells were lower in the nonglucocorticoid group than those in the healthy group from the day of admission to the 18th day and returned to normal at the period of 19-21 days. The absolute peripheral lymphocyte count (P = 0.048, effect size d = 0.727) and T cell subset count (CD3: P = 0.042, effect size d = 0.655; CD4: P < 0.01, effect size d = 0.599; and CD8: P = 0.034, effect size d = 0.550) in the nonglucocorticoid group were higher than those in the glucocorticoid group, and the difference between the groups was statistically significant. CONCLUSIONS: This study found that the use of short-term, low-dose glucocorticoids does not negatively influence the clinical outcome, without affecting the final clearance of viral nucleic acid in mild COVID-19 patients.

An evaluation of the feasibility of an expanded indication of endoscopic submucosal dissection for ulcer positive early gastric cancer: a case-control study from two medical centers.

BACKGROUND: Endoscopic submucosal dissection (ESD) has increasingly gained broad application in the treatment of early gastric cancer (EGC). This study aimed at evaluating the clinical significance of lymph node metastasis (LNM) in patients with ulcer positive [UL (+)] EGC and assessing the feasibility of expanded indications of ESD for such cases. METHODS: Patients with UL (+) EGC undergoing radical surgical resection between January 2012 and December 2018 were retrospectively reviewed. Associations between clinicopathological factors and the incidence of LNM were investigated by univariate and multivariate linear regression analysis. RESULTS: Retrospective statistical analysis was performed on 653 EGC patients. The multivariate linear regression analysis showed that the presence of LNM was significantly associated with depth of invasion (P<0.0001) and lymphatic invasion (P<0.001). The proportion of EGC patients met absolute and expanded indication of ESD with positive LNM who were subject to the criteria of curative resection was 0.75% (4/532) and 6.67% (8/120), respectively. LNM between patients, which were subject to the absolute and expanded ESD indication, is significantly different (P=0.000274). CONCLUSIONS: Our study revealed that 6.67% (8/120) of EGC patients who did not meet all criteria of curative resection were present with LNM. EGC patients with UL (+), differentiated adenocarcinoma, tumor invasion pathologically diagnosed as T1a, and tumor diameter ≤3 cm showed for ESD are suggested for a carefully weighed treatment.

[Radiological study on the cup abduction angle during total hip arthroplasty].

OBJECTIVE: To analyze the relationship among the parameters by measuring the relevant parameters of the anteroposterior X-ray of both hips in patients after total hip arthroplasty, to discuss the reliable anatomical markers and reference standards of acetabulum placement in total hip arthroplasty, and finally to accurately control the abduction angle of acetabulum. METHODS: From January 2016 to June 2017, 282 patients (235 hips) underwent total hip arthroplasty and 128 patients(157 hips) met the inclusion criteria. There were 91 males and 37 females, 82 cases of the left hip and 75 cases of the right hip; ranging in age from 22 to 78 years old, with a mean of 55.1 years old. The abduction angle(ß), ilium thickness (a), acetabular cup insertion depth (b), ischial thickness (c), acetabular cup insertion depth(d), acetabular abrasion and contusion depth(e) were measured on the postoperative AP X-ray of both hips, and the data were compared. RESULTS: There was a positive correlation between ß and b (r=0.424, P=0.000), a negative correlation between ß and d (r=-0.407, P=0.000), a positive correlation between ß and b/a (r=0.419, P=0.000), a negative correlation between ß and d/c (r=-0.472, P=0.000). There was a linear relationship between ß and b/a (t=5.753, P=0.000) and a linear relationship between ß and d/c (t=-6.671, P=0.000). CONCLUSIONS: The outreach angle is mainly controlled by the distance between the outer edge of the cup and the outer edge of the cup in the inferior portion(d) during the operation. The distance b from the outer edge of the cup can be used as a reference.

Tumor heterogeneity of gastric cancer: From the perspective of tumor-initiating cell.

Gastric cancer (GC) remains one of the most common and malignant types of cancer due to its rapid progression, distant metastasis, and resistance to conventional chemotherapy, although efforts have been made to understand the underlying mechanism of this resistance and to improve clinical outcome. It is well recognized that tumor heterogeneity, a fundamental feature of malignancy, plays an essential role in the cancer development and chemoresistance. The model of tumor-initiating cell (TIC) has been proposed to explain the genetic, histological, and phenotypical heterogeneity of GC. TIC accounts for a minor subpopulation of tumor cells with key characteristics including high tumorigenicity, maintenance of self-renewal potential, giving rise to both tumorigenic and non-tumorigenic cancer cells, and resistance to chemotherapy. Regarding tumor-initiating cell of GC (GATIC), substantial studies have been performed to (1) identify the putative specific cell markers for purification and functional validation of GATICs; (2) trace the origin of GATICs; and (3) decode the regulatory mechanism of GATICs. Furthermore, recent studies demonstrate the plasticity of GATIC and the interaction between GATIC and its surrounding factors (TIC niche or tumor microenvironment). All these investigations pave the way for the development of GATIC-targeted therapy, which is in the phase of preclinical studies and clinical trials. Here, we interpret the heterogeneity of GC from the perspectives of TIC by reviewing the above-mentioned fundamental and clinical studies of GATICs. Problems encountered during the GATIC investigations and the potential solutions are also discussed.

Portulacaoleraceal extract alleviates trinitrobenzene sulfonic acid-induced colitis in rats.

Portulacaoleraceal (POL) has been widely used as an edible plant and a folk medicine in many countries, due to its several health benefits. This study examined the effects of POL on trinitrobenzene sulfonic acid (TNBS)-induced colitis via enema administration. Sixty male Sprague-Dawley rats were randomly divided into five groups: untreated, TNBS, TNBS + POL 10 g/kg, TNBS + POL 5 g/kg and TNBS + POL 2.5 g/kg groups. Rats were subjected to enema treatment once a day for 10 consecutive days with POL extract or distilled water after induction of TNBS. The changes of body weight, histological parameters, myeloperoxidase (MPO), superoxide dismutase (SOD), nitric oxide synthase activity (NOS), malondialdehyde (MDA) and nitric oxide (NO) levels in colon tissues were investigated. After POL extract treatment, body weights of rats significantly increased, macroscopic and microscopic damage scores reduced, MPO and NOS activity, as well as MDA and NO level significantly decreased, while SOD activity increased in a dose-dependent manner in the TNBS + POL groups compared with the TNBS group. Our results demonstrated that POL enema treatment attenuated pathologic changes of TNBS-induced colitis in rats through restoring colonic damage and reducing inflammatory response in the intestine. Thus, POL enema might be considered as a potential effective treatment for ulcerative colitis patients.

Successful endoscopic hemoclipping of massive lower gastrointestinal bleeding from paratyphoid A fever.

Paratyphoid fever can be complicated by massive lower gastrointestinal bleeding with ileocolonic ulcerations, which are commonly localized using colonoscopy. The most common manifestations include multiple, variable-sized, round or oval-shaped, punched-out ulcers. Occasionally, massive lower gastrointestinal bleeding can occur from erosion of blood vessels. We present a rare case of severe lower gastrointestinal bleeding due to paratyphoid A fever that was successfully controlled with hemoclippings. A 30-year-old man experienced high fever and hematochezia whose blood culture showed Salmonella paratyphi A. A complete colonoscopy was successfully performed up to the level of the terminal ileum, which showed multiple, shallow, ulcerated lesions over the entire terminal ileum. A bleeding vessel was seen in one of the ulcers, with overlaying blood clots. Endoscopic hemostasis was successfully performed with four pieces of endoclip and without immediate complication. This report highlights the use of colonoscopy and endoscopic therapy with endoclips for lower gastrointestinal bleeding, which should be considered before surgery.

Massive lower gastrointestinal bleeding from the appendix.

Massive rectal bleeding from the appendix, considered a rare case of lower gastrointestinal bleeding, is not easily recognized by various diagnostic modalities. A multidisciplinary approach for both a diagnosis and a differential diagnosis is important because the identification of the bleeding site is crucial to proceed to a proper intervention and there are various causes of appendiceal bleeding. Because early colonoscopy plays an important role in the diagnosis and management of lower gastrointestinal hemorrhage, we report a case of a life threatening massive rectal bleeding from the appendix diagnosed by colonoscopy. We also present a review of the literature.

[Effects of experimental liver injury on the intestinal barrier in rats.].

OBJECTIVE: To study the effects of experimental liver injury on the intestinal barrier, and to evaluate the significance of plasma D(-)-lactate, diamine oxidase (DAO) and endotoxin in live injury. METHODS: Fifty-five rats were randomized into the acute liver failure group (group C, n = 25), acute liver injury group (group B, n = 15), and control group (group A, n = 15). The concentrations of D(-)-lactate, DAO and endotoxin in plasma were detected by spectrophotograph. The morphology and subcellular structure were observed under optical microscope and transmission electron microscope. RESULTS: Acute liver failure and acute liver injury models were established successfully. The concentrations of D(-)-lactate and DAO in the plasma of experimental groups (group B and C) were significantly higher than those in the control group (P less than 0.05); the concentration of intestinal DAO in experimental groups were significantly lower than that in the control group (P less than 0.05); the level of endotoxin in C group was significantly higher than that in group A and group B (P less than 0.05). CONCLUSION: Liver injury induces hyperpermeability of the rat intestinal mucosal barrier, plasma D(-)-lactate and DAO are sensitive markers for early diagnosis of liver injury, plasma endotoxin may accelerate deterioration of liver function.

[Liver histopathology, clinical features and prognostic factors of primary biliary cirrhosis: an analysis of 60 cases].

OBJECTIVE: Clinical and liver pathological features of 60 primary biliary cirrhosis (PBC) patients were reviewed to identify prognostic factors in order to improve the diagnosis and treatment of the disease. METHODS: The general conditions, clinical manifestations, serum biochemical and immunological changes, and liver pathological findings were assessed in 60 PBC patients. All cases were followed up and 5 variables were studied by univariate analysis; the variables linked with survival were included in a Cox model. RESULTS: Forty-eight patients were females (80%), 12 were males (20%), and the mean age at their diagnoses was (52.5+/-9.4). The symptoms most frequently complained about were jaundice (61.6%), fatigue (51.6%), anorexia (43.3%) and pruritus (25%). Serum alkaline phosphatase (ALP) and glutamyl transpeptidase (GGT) levels were markedly elevated in the majority of the patients [(242.3+/-137.1) U/L and (250.6+/-216.1) U/L, respectively], whereas ALT and AST levels were mildly to moderately elevated [(185.8+/-269.1) U/L and (172.5+/-163.6) U/L, respectively]. Thirty-two patients (53.3%) had a total bilirubin level of > or = 34.2 micromol/L. Twenty-eight patients (59.5%) had elevated serum IgM and 41 patients (68.3%) were anti-mitochondrial antibody AMA/AMA-M2 positive. Forty-two of the 60 patients had liver biopsies. The liver pathological changes: 33.3% of the cases were in I or II stage and 66.6% in III or IV stage. The follow up results: Five patients died of liver failure or massive upper gastrointestinal bleeding; 45 were still alive; the average survival period was 3.92 years; 10 patients were lost in the follow-up. With multivariate analysis (Cox model), age, level of total bilirubin and the stage of the liver pathological changes were found to be independent factors linked to the survival of the patients. CONCLUSION: PBC may not be a rare liver disease in China. The awareness to recognize PBC is important in making an early diagnosis and treatment.