[Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases].

Objective: To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM). Methods: This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging (M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results: (1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95%CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference (P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options (HR=1.98, 95%CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients' prognosis (HR=2.01, 95%CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors (HR=2.84, 95%CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver (HR=2.06, 95%CI 1.19 to 3.57, P=0.010). Conclusions: In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

[Efficacy analysis of hepatic arterial infusion chemotherapy combined with targeted and immune therapy followed by 125I seeds implantation in the treatment of hepatocellular carcinoma with portal vain tumor thrombus].

Objective: To investigate the safety and efficacy of Hepatic Arterial Infusion Chemotherapy(HAIC) combined with targeted and immune therapy followed by 125I seeds implantation in portal vain tumor thrombus (PVTT) in the treatment of hepatocellular carcinoma(HCC) with PVTT. Methods: A retrospective study was performed on the clinical data of 21 patients [ (11 men, 10 women) aged 34-73 (52.6±13.7) years] with HCC with PVTT in The First Affiliated Hospital of Zhengzhou University from October 2020 to October 2022, all of them were treated with HAIC plus targeted and immune therapy,and 125I seeds implanted into PVTT. The patients were followed up to January 2023, the efficacy was evaluated according to the modified version of the solid tumor efficacy evaluation criteria (mRECIST). The progression-free survival (PFS) rate, overall survival(OS) rate and portal tumor thrombus control rate at 3, 6, 12 and 18 months after treatment were recorded, and PFS and OS time were followed up. The changes of liver function, AFP, coagulation function and adverse events were observed. Results: Each patient received 2 to 7 (mean: 3.3±1.2) cycles of HAIC. 10-37 seeds (mean:16.6±6.7) were implanted per patients. The median follow-up time was 15 (range from 5 to 25) months.During the follow-up time, 15 patients showed progression and 6 patients died, and the PFS rates at 3, 6, 12, and 18 months after treatment were 90.5%, 71.4%, 42.9%, and 23.8%, respectively, and at 3, 6, 12, and 18-month OS rates were 100%, 100%, 81.0%, and 61.9%, respectively.The PVTT control rates at 3, 6, and 12 months were 90.5%, 90.5%, and 62.5%, respectively. Overall efficacy evaluation of CR rate 0, PR rate 47.6% (10/21), SD rate 38.1% (8/21), and PD rate 14.3% (3/21). The total incidence of treatment-related adverse events was 100%.Grade 3 treatment related adverse events were observed for 4 cases, the rest wereⅠtoⅡadverse events. Right upper abdominal pain, fever and hemorrhage in liver capsule related to the procedures were observed in 11(52.4%), 5(23.8%) and 3(14.3) patients, respectively. Conclusion: HAIC combined with targeted and immune therapy followed by 125I seeds implantation in PVTT is a safe and efficacy therapy for HCC with PVTT.

Locoregional radiotherapy improves survival outcomes in de novo metastatic nasopharyngeal carcinoma treated with chemoimmunotherapy.

BACKGROUND: We aimed to investigate the efficacy of locoregional radiotherapy (LRRT) in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC) receiving chemotherapy combined with anti-programmed cell death receptor-1 monoclonal antibodies (anti-PD-1 mAbs) as first-line treatment and identify optimal candidates for LRRT. MATERIALS AND METHODS: We enrolled patients with dmNPC receiving platinum-based palliative chemotherapy and anti-PD-1 mAbs followed or not followed by LRRT from four centers. The endpoints were progression-free survival (PFS), objective response rate (ORR), and overall survival (OS). We used the inverse probability of treatment weighting (IPTW) to balance the baseline characteristics of the LRRT and non-LRRT groups to minimize selection bias before comparative analyses. Multivariate analyses were carried out using the Cox proportional hazards model. RESULTS: We included 163 patients with dmNPC (median follow-up: 22 months). The median PFS was 20 months, and the ORR was 92.0%; the median OS was not achieved. After IPTW adjustments, patients who received LRRT had a significant survival benefit over those not receiving LRRT (median PFS: 28 versus 15 months, P < 0.001). The Epstein-Barr virus DNA (EBV DNA) level after four to six cycles of anti-PD-1 mAbs [weighted hazard ratio (HR): 2.19, 95% confidence interval (CI) 1.22-3.92, P = 0.008] and LRRT (weighted HR: 0.58, 95% CI 0.34-0.99, P = 0.04) were independent prognostic factors. Patients with undetectable EBV DNA levels after four to six cycles of anti-PD-1 mAbs (early EBV DNA clearance) benefitted from LRRT (HR: 0.41, 95% CI 0.22-0.79, P = 0.008), whereas those with detectable levels did not (HR: 1.30, 95% CI 0.59-2.87, P = 0.51). CONCLUSIONS: Palliative chemotherapy combined with anti-PD-1 mAbs followed by LRRT was associated with improved PFS in patients with dmNPC, especially for patients with early EBV DNA clearance.

[Distribution characteristics of tumor infiltrating lymphocytes in EBV-associated lymphoepithelioma-like carcinoma and their clinical significance].

Objective: To investigate the association between the distribution of tumor infiltrating lymphocytes (TIL) in EBV associated lymphoepitheliomatoid carcinoma (LELC) and the pathological subtypes of LELC, as well as the clinical significance of TIL distribution. Methods: The LELC patients with sufficient tumor tissues, complete clinical data and positive EBER, who visited Zhejiang Cancer Hospital, Hangzhou, China from January 2006 to October 2018, were selected. Various immunohistochemical markers (CD20, CD138, CD4, CD8, CD56 and FOXP3) were examined for TIL typing. Two pathologists reviewed the hematoxylin and eosin (HE) staining sections and interpreted the immunohistochemical results. Correlation analysis was used to evaluate the relationship between the distribution of TIL subgroups and LELC's pathological characteristics. Survival analyses were conducted to study the prognostic values of TIL subgrouping. Results: A total of 102 patients with EBV related LELC were included. 46 of them were classic LELC (c-LELC) with rich interstitial TIL, and 56 were non-classic LELC (n-LELC) with relatively fewer interstitial TIL. The results of TIL analysis showed that all subtypes of c-LELC were rich in TIL, with B lymphocytes as the dominant subgroup. The number of TIL in n-LELC was fewer than that in c-LELC, with T lymphocytes as the dominant subgroup. There was no significant difference in the distribution of plasma cells between the two groups. Survival analysis showed that the total number of TIL, and the infiltrations of CD20+B cells, CD4+T cells, and FOXP3+Treg cells were associated with better overall survivals (P=0.004, 0.003, 0.008 and 0.025, respectively) and disease-free survivals (P=0.011, 0.003, 0.038 and 0.041, respectively) in patients with LELC. Conclusions: The morphologic subtypes of EBV-related LELC have different tumor immune characteristics. The total number of TIL in the stroma of c-LELC is significantly higher than that of n-LELC. Interestingly, B lymphocytes are the dominant TIL in c-LELC, while T lymphocytes are the dominant TIL in n-LELC. The infiltration of TIL, CD20+B cells, CD4+T cells and FOXP3+Treg cells in LELC may suggest a better prognosis.

[Evolution and progress of surgical intervention strategies for acute pancreatitis].

Acute pancreatitis is one of the common surgical acute abdominal diseases. Since people first recognized acute pancreatitis in the middle of the nineteenth century, a diversified minimally invasive treatment model with standardization has been formed today. According to the main line of surgical intervention of acute pancreatitis treatment,this period can be roughly divided into five stages:exploration stage, conservative treatment stage, pancreatectomy stage, debridement and drainage of the pancreatic necrotic tissue stage, and minimally invasive treatment as the first choice led by the multidisciplinary team mode stage. Throughout history, the evolution and progress of surgical intervention strategies for acute pancreatitis cannot be separated from the progress of science and technology, the update of treatment concepts and the further understanding of the pathogenesis. This article will summarize the surgical characteristics of acute pancreatitis treatment at each stage to explain the development of surgical treatment of acute pancreatitis,to help investigate the development of surgical treatment of acute pancreatitis in the future.

The role of lymphocyte count in the early diagnosis of surgical site infection following posterior lumbar fusion.

OBJECTIVE: This study aimed to explore the early diagnostic value of lymphocyte count in the early diagnosis of surgical site infection (SSI) following posterior lumbar fusion. PATIENTS AND METHODS: In this study, we retrospectively analyzed the data from a total of 37 patients with lumbar SSI from Guizhou  Province Orthopaedic Hospital and Nanyang Central Hospital, 2008.1-2018.11, and 104 patients without SSI. We analyzed the C-reactive protein (CRP) level, white blood cell count (WBC) and differential count before instrumented lumbar fusion at 3 and 7 days postoperatively. The significance of the differences was evaluated by one-way ANOVA, followed by Fisher's test. The parameters mentioned above were analyzed on postoperative days 3 and 7 using the receiver operating characteristic curve and the area under the curve (AUC). Furthermore, the analyses were conducted by SPSS 22.0 software. RESULTS: The lymphocyte count in the SSI group on postoperative day 3 was significantly lower than that in the no-SSI group after surgery (p=0.000). According to the ROC curve analysis of related parameters on postoperative day 3, the AUC value of lymphocytes (0.840) was significantly larger than the AUC value of C-reactive protein (0.749). CONCLUSIONS: The lymphocyte count and C-reactive protein level on postoperative day 3 are reliable predictors of infection.

[Imaging classification and analysis of the diagnosis and treatment of infected pancreatic necrosis:a report of 126 cases].

Objective: To explore the clinical characteristics of various types of infected pancreatic necrosis(IPN) and the prognosis of different treatment methods in the imaging classification of IPN proposed. Methods: The clinical data of 126 patients with IPN admitted to the Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University from December 2018 to December 2021 were analyzed retrospectively. There were 70 males(55.6%) and 56 females(44.4%), with age(M(IQR)) of 44(17)years (range: 12 to 87 years). There were 67 cases(53.2%) of severe acute pancreatitis and 59 cases (46.8%) of moderately severe acute pancreatitis. All cases were based on the diagnostic criteria of IPN. All cases were divided into Type Ⅰ(central IPN)(n=21), Type Ⅱ(peripheral IPN)(n=23), Type Ⅲ(mixed IPN)(n=74) and Type Ⅳ(isolated IPN)(n=8) according to the different sites of infection and necrosis on CT.According to different treatment strategies,they were divided into Step-up group(n=109) and Step-jump group(n=17). The clinical indicators and prognosis of each group were observed and analyzed by ANOVA,t-test,χ2 test or Fisher exact test,respectively. Results: There was no significant difference in mortality, complication rate and complication grade in each type of IPN(all P>0.05). Compared with other types of patients, the length of stay (69(40)days vs. 19(19)days) and hospitalization expenses(323 000(419 000)yuan vs. 60 000(78 000)yuan) were significantly increased in Type Ⅳ IPN(Z=-4.041, -3.972; both P<0.01). The incidence of postoperative residual infection of Type Ⅳ IPN was significantly higher than that of other types (χ2=16.350,P<0.01). There was no significant difference in the mortality of patients with different types of IPN between different treatment groups. The length of stay and hospitalization expenses of patients in the Step-up group were significantly less than those in the Step-jump group(19(20)days vs. 33(35)days, Z=-2.052, P=0.040;59 000(80 000)yuan vs. 122 000(109 000)yuan,Z=-2.317,P=0.020). Among the patients in Type Ⅳ IPN, the hospitalization expenses of Step-up group was significantly higher than that of Step-jump group(330 000(578 000)yuan vs. 141 000 yuan,Z=-2.000,P=0.046). The incidence of postoperative residual infection of Step-up group(17.4%(19/109)) was significantly lower than that of Step-jump group(10/17)(χ2=11.980, P=0.001). Conclusions: Type Ⅳ IPN is more serious than the other three types. It causes longer length of stay and more hospitalization expenses. The step-up approach is safe and effective in the treatment of IPN. However, for infected lesions which are deep in place,difficult to reach by conventional drainage methods, or mainly exhibit "dry necrosis", choosing the step-jump approach is a more positive choice.

[Sulforaphane reverses Aß fiber-mediated M1 type microglia polarization and neuroinflammation-mediated necroptosis of neural stem cells by downregulating the MAPK/NF-κB signaling pathways].

OBJECTIVE: To explore the effects of sulforaphane (SFN) and Aß25-35 fibers (fAß25-35) on M1/M2 polarization of BV-2 cells and neuroinflammation-mediated programmed necrosis of neural stem cells. METHODS: BV-2 cells treated with different concentrations of fAß25-35 and SFN were examined for changes in cell viability using the CCK-8 kit. The effect of fAß25-35 alone or in combination with SFN or SB203580 on expressions of IL-6 and TNF-α mRNA and proteins were assessed in BV-2 cells using RT-qPCR and ELISA. CD16/32 and CD206 in the treated cells were analyzed with flow cytometry, and the cellular expressions of p-p38 and p-p65 protein were detected with Western blotting. C17.2 cells co-cultured with BV-2 cells for 24 h were examined for p-mlkl protein expression using Western blotting. RESULTS: fAß25-35 at the concentration of 6.25 µmol/L significantly increased the viability of BV-2 cells (P < 0.01) whereas fAß25-35 beyond 50 µmol/L decreased the cell viability (P < 0.0001). Treatment of BV-2 cells with SFN below 10 µmol/L for 24 h did not significant affect the cell viability (P > 0.05). BV-2 cells treated with fAß25-35 alone, as compared with the cells in the other 3 groups, showed significantly increased IL-6 and TNF-α mRNA and protein expressions (P < 0.001), enhanced CD16/32 expression (P < 0.05), lowered CD206 expression (P < 0.01), and increased protein expressions of p-p38 and p- p65 (P < 0.01). C17.2 cells co-cultured with BV-2 cells treated with fAß25-35, compared with the combined treatments, showed a significant reduction in the protein expression of p-mlkl (P < 0.05). CONCLUSION: SFN reverses M1 type microglia polarization and neuroinflammation-mediated programmed necrosis of neural stem cells by downregulating the MAPK/NF-κB signaling pathway in Aß25-35-activated BV-2 cells.

[Treatment choices for infected pancreatic necrosis:surgery debridement or endoscopy drainage?]

Infected pancreatic necrosis (IPN) is a crucial reason for the poor prognosis of patients with acute pancreatitis,which is complicated and difficult to predict the outcomes. Surgery is an important way to cure IPN,and "step-up approach" is the mainstream mode of IPN treatment. In the era of minimally invasive surgery,the full course endoscopic treatment of IPN has been gradually hot and achieved good outcomes as endoscopic technology' improvement. However,it is controversial that whether technique is better for IPN by surgery debridement or endoscopy drainage,and there is no consensus on the scope of applicability and the timing of intervention. The paper aims to explore the intervention methods,indications and timing of endoscopic and surgical treatment of IPN and elaborate the selection strategies of them in clinical practice,so as to develop individualized treatment options,accurately implement minimally invasive intervention and improve the prognosis.

MicroRNA-4463 facilitates the development of colon cancer by suppression of the expression of PPP1R12B.

PURPOSE: In the present work, we investigated the expression pattern of miR-4463 in the non-metastasis and metastasis colorectal cancer (CRC) patients and its regulation axis. METHODS: RT-qPCR assay was performed to assess miR-4463 expression in the serum and tissues of patients with non-metastasis and metastasis, and in the CRC cell lines. MTT assay, colony formation assay, transwell assay, and flow cytometry assay were used to examine the role of miR-4463 in CRC cell viability, proliferation, and migration. Bioinformatic analysis was used to identify the potential target gene of miR-4463, and the targeting relationship between miR-4463 and PPP1R12B was verified in vitro using dual luciferase assay. Western blotting assay was used to determine the protein level of the target gene PPP1R12B in CRC cells under the transfections of miR-4463 mimic, inhibitor and vectors overexpressing PPP1R12B. RESULTS: miR-4463 was markedly increased in the non-metastasis CRC tissues, and increased even higher in the metastasis CRC tissues, while miR-4463 expression had no significant difference in serum from non-metastasis and metastasis CRC samples. Besides, miR-4463 was upregulated in CRC cell lines. Functionally, miR-4463 promoted CRC cell proliferation, migration, and inhibiting cell apoptosis. Further analysis revealed that the miR-4463/PPP1R12B axis was responsible for the role of this miRNA. CONCLUSION: We reported the roles of miR-4463 in CRC proliferation and migration, supporting that miR-4463 could be a potential predictive diagnostic marker for colon cancer.

The effect of botulinum toxin A in unilateral cleft lip scar: comparison of results with different sites of injection.

Botulinum toxin type A (BTA) injections into the subjacent orbicularis oris muscle have been shown to improve appearance and produce narrower cheiloplasty scars. This study was performed to determine the effect of BTA injected at different sites on the unilateral cleft lip scar and cleft side nostril width. A double-blind, randomized prospective trial was conducted involving 64 consecutive patients with unilateral cleft lip undergoing primary cheiloplasty between September 2016 and January 2019. The patients were randomized to receive BTA injections either into the subjacent orbicularis oris muscle (4 points group) or into the bilateral nasolabial fold region (6 points group) during cheiloplasty. The scars were assessed by photographic scar width measurements and Vancouver scar scale assessment tool. The cleft side nostril width was compared to the non-cleft side width. Fifty-six patients completed the trial, 24 in the 4 points group and 31 in the 6 points group. There was no significant difference in scar width or nostril width measurements between the groups at the end of follow-up. The Vancouver scar scale assessment was also similar between the groups. There was no significant difference in scar width or nostril width measurements after cleft lip repair between patients treated with botulinum toxin injections to the subjacent orbicularis oris muscle and patients treated with injections in the nasolabial region.

Adamts18 Deficiency Causes Spontaneous SMG Fibrogenesis in Adult Mice.

Chronic sclerosing sialadenitis of the submandibular gland (also known as Küttner tumor) is characterized by concomitant swelling of the submandibular glands secondary to strong lymphocytic infiltration and fibrosis. The pathogenesis of this disease has been unclear, but it is associated with immune disorders. ADAMTS18 is a member of the ADAMTS superfamily of extracellular proteinases. In this study, we showed that Adamts18 is highly expressed in submandibular salivary gland (SMG) during embryonic development and decreases but is retained in adult SMG tissue in mice. Adamts18 deficiency led to reduced cleft formation and epithelial branching in embryonic SMG before embryonic day 15.5 in mice. No significant histologic changes in the later stages of branching or the morphology of SMG were detected in Adamts18-/- mice. However, Adamts18 deficiency causes spontaneous SMG fibrogenesis and fibrosis in adult mice. At 8 wk of age, Adamts18-/- mice began to manifest the first signs of pathologic changes of mild fibrosis and CD11b+ cell infiltration in SMG tissues. At ≥8 mo, all male and female Adamts18-/- mice developed unilateral or bilateral SMG scleroma that is similar to patients with chronic sclerosing sialadenitis of the submandibular gland. Adamts18-/- mice also showed secretory dysfunction and severe dental caries. Histologically, SMG scleroma is characterized by progressive periductal fibrosis, acinar atrophy, irregular duct ectasis, and dense infiltration of IgG-positive plasma cells. A significant infiltration of CD4+ T lymphocytes and CD11b+ monocytes and macrophages was also detected in the SMG scleroma of Adamts18-/- mice. The levels of TGF-ß1, IL-6, and IL-33 were significantly increased in Adamts18-/- SMGs, which induces chronic inflammation and myofibroblast activation, ultimately leading to fibrosis. This study indicates that Adamts18 regulates the early branching morphogenesis of embryonic SMG and plays a role in protecting from spontaneous SMG fibrogenesis via modulating local inflammation, autoimmune reaction, and myofibroblast activation in adult mice.

[Study on the safety and clinical efficacy of osteotomy after halo pelvic traction in severe scoliosis accompanied with split cord malformation].

Objective: To investigate the safety and clinical efficacy of osteotomy after halo pelvic traction in severe scoliosis accompanied with split cord malformation. Methods: The clinical data of 14 patients with severe scoliosis accompanied with split cord malformation admitted to the Department of Spinal Surgery, Guizhou Orthopedic Hospital from August 2015 to August 2019 were retrospectively analyzed.There were 6 males and 8 females, aged (19.8±5.0) years (range:13 to 34 years). All patients received spinal orthopedic surgery after halo pelvic traction for 3 to 7 weeks.The data of traction time, height, Cobb angle in the main curved coronal plane and sagittal plane, lung function and nutritional status of the patient were collected before and after the treatment. Paired t test was used to compare the evaluation indexes. Results: The traction time of the 14 patients was (35.2±8.3)days (range:20 to 49 days), and the height of them increased from (156.7±7.6)cm (range:141 to 166 cm) before traction to (167.0±6.4)cm (range:154 to 177 cm) after traction（t=-10.49，P<0.01）. The Cobb angle on the main curved coronal plane decreased from (117.4±17.2) ° (range: 91°to 176°) before traction to (56.4±8.1) ° (range:44°to 68°) after traction（t=13.90，P<0.01）. The sagittal Cobb angle decreased from (92.5±11.6) ° (range:62°to 132°) before traction to (41.7±7.7) °(range:29°to 51°) after traction（t=12.11，P<0.01）. No complications such as loosening of nailing and infection occurred during traction, and no decrease of nerve function occurred. Nine patients underwent single segment acromial transpedicle osteotomy and five underwent double segment adjacent asymmetric shortening osteotomy. None of the patients underwent longitudinal fracture resection. The lung function and nutritional status were improved after traction and surgery(all P<0.01). Postoperative follow-up was (22.5±9.1)months (range:12 to 36 months). At the last follow-up, the coronal Cobb angle was (56.3±7.1) °, and the sagittal Cobb angle was (37.7±6.5) °, showing no statistically significant difference from the angle after traction(t=0.16,P=0.88; t=2.28,P=0.32). There was no loss of orthopedic angle. None of the patients had internal fixation displacement, loosening or fracture. Conclusion: The treatment of severe scoliosis with accompanied with split cord malformation by halo pelvic traction is safe and effective, which is worthy of further confirmation by large sample study.

Cytomegalovirus infection as an underestimated trigger for checkpoint inhibitor-related pneumonitis in lung cancer: a retrospective study.

OBJECTIVES: Checkpoint inhibitor-related pneumonitis (CIP) is a rare but potentially fatal complication of immune checkpoint inhibitors (ICIs). At present, the mechanism of CIP is not completely clear. Cytomegalovirus (CMV) infection is widespread in the population. Chemotherapy and radiotherapy can lead to the reactivation of CMV. We aimed to investigate the association between CMV infection and CIP. MATERIALS AND METHODS: We retrospectively identified all lung cancer patients treated with ICIs at our institute from January 2016 to May 2020. The association between the development of CIP and CMV infection status was analyzed. RESULTS: Among 251 cases analyzed, 29 (11.6%) patients with CIP were identified, of whom 12 (4.78%) cases had grade 3-4 CIP. All 12 patients with grade 3-4 pneumonitis were CMV-IgG-positive, indicating a previous CMV infection. Except for one CMV-DNA-positive patient, the other patients were CMV-DNA-negative. All but one patient was CMV pp65 antigen-positive, indicating an early reactivation of the virus. The histological features of CMV pneumonia were not found in all available lung tissues, including lung transplantation pathology in one patient and lung biopsies in three patients. Except for one patient who received delayed antiviral therapy, the symptoms improved after glucocorticoid combined with antiviral therapy. CONCLUSIONS: The use of ICIs can restore the immune function and cause an immune response to CMV antigen while the infection is still latent. Our study suggests that CIP may be an immune reconstitution syndrome associated with CMV infection. CMV infection may represent a potentially important trigger for CIP. Patients with severe CIP should be vigilant against CMV infection. The early use of glucocorticoid combined with antiviral therapy is pivotal to good prognosis.

Predictive Value of Neutrophil-to-Lymphocyte Ratio for Differentiating Organic Dyspepsia from Functional Dyspepsia

ABSTRACT Objective: Dyspepsia, one of the most commonly seen symptoms, can be due to organic dyspepsia (OD) or functional dyspepsia (FD). The aim of this study is to evaluate neutrophil-tolymphocyte ratio (NLR) for the predictability of OD due to peptic ulcer disease (PUD) and gastric cancer (GC). Methods: We investigated retrospectively the patients with dyspepsia who underwent endos-copy. The study included 119 patients with OD (41 patients with biopsy-proven GC and 78 patients with PUD) and 100 patients with FD diagnosed. Results: The NLR among the patients with GC and PUD was significantly higher than FD subject (p < 0.001 each). The NLR in patients with GC was also significantly higher than that in patients with PUD (p < 0.005). When OD was compared with FD, NLR and white blood cell were statistically significantly higher (p < 0.001 and p < 0.05 respectively). The best predictive cut-off value of NLR was 1.72 with a specificity of 63% and a sensitivity of 66% for OD, on receiver-operating characteristic curve analysis. Conclusion: Neutrophil-to-lymphocyte ratio was higher in patients with OD compared with those with FD, and even higher in patients with GC. Our findings suggest that NLR should be calculated in patients with dyspepsia and patients with high levels of NLR should undergo endoscopy.

LncRNA CASC19 contributed to the progression of pancreatic cancer through modulating miR-148b/E2F7 axis.

OBJECTIVE: Cancer susceptibility 19 (CASC19), a crucial lncRNA associated with multiple cancers, has been reported to play a vital role in the progression of human malignant tumors. However, the underlying mechanism of CASC19 in pancreatic cancer (PC) was still unknown. The purpose of this study was to explore the biological and clinical significance of CASC19 in PC. PATIENTS AND METHODS: RT-qPCR assay was adopted to analyze CASC19 expression in PC tissues and cell lines. Furthermore, the correlation between the CASC19 level and the survival rate of PC patients was assessed by Kaplan-Meier analysis. Bioinformatics analysis and Luciferase reporter assay were utilized to confirm the interaction between miR-148b and CASC19 or E2F7. Cell viability, migration, invasion, and apoptosis were analyzed using MTT, transwell, and TUNEL assays. RESULTS: The results elucidated that CASC19 expression was markedly increased in PC tissues and cell lines. Patients with high expression of CASC19 had a short survival time. Silencing of CASC19 attenuated PC cell proliferation, migration, and invasion. Moreover, we identified that miR-148b was a target of CASC19. CASC19 was negatively correlated with miR-148b and positively correlated with E2F7. The inhibitory effect of CASC19 knockdown on the progression of PC was reversed by the down-regulation of miR-148b or up-regulation of E2F7. CONCLUSIONS: These results demonstrated that CASC19 participated in the development of PC. The CASC19/miR-148b/E2F7 axis might be a new study direction for PC treatment.