During the Omicron Pandemic Wave, the Severe Systemic Inflammatory Status of COVID-19 Indicated a Higher Risk of In-Hospital Mortality and Mediated the Clinical Efficacy of Corticosteroids.

Background: For the distinct immune/inflammatory responses from Omicron variant infection, this study aimed to investigate the diagnostic efficacy of systemic inflammatory indicators and the clinical efficacy of corticosteroids on the in-hospital mortality among COVID-19 patients. Methods: Under a retrospective cohort study, 1081 COVID-19 patients were recruited from Beijing Youan Hospital, Capital Medical University between November 16, 2022 and January 30, 2023. We chose neutrophil-to-lymphocyte ratio (NLR), CRP-to-lymphocyte ratio (CLR), and CRP-to-albumin ratio (CAR) as the systemic inflammatory indicators. Receiver operating curve (ROC) and multivariate logistic regression analysis were used to determine the diagnostic efficacy of systemic inflammatory indicators and the association between systemic inflammatory indicators and in-hospital mortality. Results: Among 684 patients included in analysis, 96 died during hospitalization. NLR, CLR and CAR performed well (with an area under the curve (AUC) greater than 0.75) in discriminating in-hospital mortality among COVID-19 patients. The severe status of systemic inflammation, with optimal cut-off value derived from ROC analysis, significantly associated higher risk of in-hospital mortality (OR = 3.81 for NLR ≥ 6.131; OR = 3.76 for CLR ≥ 45.455; OR = 5.10 for CAR ≥ 1.436). Corticosteroids use within 72 hours of admission increased the in-hospital mortality 2.88-fold for COVID-19 patients. In the subgroup of patients with severe systemic inflammation, corticosteroids increased the risk of in-hospital mortality (OR = 2.11 for NLR, p = 0.055; OR = 2.94 for CLR, p = 0.005; OR = 2.31 for CAR, p = 0.036). Conclusion: Systemic inflammatory indicators had good diagnostic performance for in-hospital mortality. Patients with severe systemic inflammatory status should not receive corticosteroid treatment and further studies are warranted for confirmation.

Reprogramming of lipid metabolism in hepatocellular carcinoma resulting in downregulation of phosphatidylcholines used as potential markers for diagnosis and prediction.

BACKGROUND: Aberrant methylation and metabolic perturbations may deepen our understanding of hepatocarcinogenesis and help identify novel biomarkers for diagnosing hepatocellular carcinoma (HCC). We aimed to develop an HCC model based on a multi-omics. RESEARCH DESIGN AND METHODS: Four hundred patient samples (200 with HCC and 200 with hepatitis B virus-related liver disease (HBVLD)) were subjected to liquid chromatography-mass spectrometry and multiplex bisulfite sequencing. Integrative analysis of clinical data, CpG data, and metabolome for the 20 complete imputation datasets within a for-loopwas used to identify biomarker. RESULTS: Totally, 1,140 metabolites were annotated, of which 125 were differentially expressed. Lipid metabolism reprogramming in HCC, resulting in phosphatidylcholines (PC) significantly downregulated, partly due to the altered mitochondrial beta-oxidation of fatty acids with diverse chain lengths. Age, sex, serum-fetoprotein levels, cg05166871,cg14171514, cg18772205, PC (O-16:0/20:3(8Z, 11Z, 14Z)), and PC (16:1(9Z)/P-18:0) were used to develop the HCC model. The model presented a good diagnostic and an acceptable predictive performance. The cumulative incidence of HCC in low- and high-risk groups of HBVLD patients were 1.19% and 21.40%, respectively (p = 0.0039). CONCLUSIONS: PCs serve as potential plasma biomarkers and help identify patients with HBVLD at risk of HCC who should be screened for early diagnosis and intervention.

Association between MTTP genotype (-493G/T) polymorphism and hepatic steatosis in hepatitis C: a systematic review and meta-analysis.

BACKGROUND: Hepatitis C has been associated with the development of hepatic steatosis, which increases the risk of liver cancer. The microsomal triglyceride transporter protein (MTTP), is a lipid transport protein that mediates lipid metabolism and CD1d antigen presentation. The study aimed to explore the association between MTTP genotype (-493G/T) polymorphism and hepatic steatosis in hepatitis C. METHODS: The database "Pubmed, Cochrane library, CNKI, Web of science, Embase and CBM" were retrieved to identify the literature. The quality of the selected literature was evaluated using the "the Newcastle-Ottawa Scale" (NOS). Relevant data was extracted and analyzed using the Stata software. Heterogeneity was expressed by "Cochran's Q and I2", with I2 ≥ 50% or P < 0.05 indicating high heterogeneity. A random-effects model and subgroup analysis were conducted to identify the sources of heterogeneity. We also used "Funnel plots", "Egger's tests" and "Begg's tests" to evaluate biases in the literature. RESULTS: The study found a significant and positive association between liver steatosis and the HCV genotype 3 with a dominant model of the MTTP genotype (-493G/T) (OR = 11.57, 95%CI: 4.467-29.962, P < 0.001). In contrast, no correlation was found between hepatic steatosis and either the recessive, homozygous or heterozygous models (OR = 1.142, P = 0.5; OR = 1.581, P = 0.081; OR = 1.029, P = 0.86). There was no significant publication biases, as measured by the Funnel plot, and the Egger's and Begg's tests. Finally, sensitivity analysis showed the obtained results are stable. CONCLUSIONS: Dominant mutations in the T allele of the MTTP genotype (-493G/T) increase susceptibility to hepatic steatosis in patients presenting with the HCV genotype 3.

Real-World Effectiveness of Nirmatrelvir/Ritonavir and Dexamethasone Among Hospitalized Patients with COVID-19: A Prospective Cohort Study.

Purpose: Anti-viral and anti-inflammatory therapies were effective in altering virus repletion and immune dysregulation in Coronavirus Disease 2019 (COVID-19) patients. This study aimed to explore the effect of combination therapy on disease progression in a real-world setting. Patients and Methods: A total of 836 patients confirmed with SARS-CoV-2 infection participated in the study from 15 November to 25 December 2022 at Beijing Youan Hospital, Capital Medical University. A prospective cohort study was implemented to investigate the prognostic effect of the combination therapy on virus shedding and clinical recovery. Results: About 78% of patients used nirmatrelvir/ritonavir (N/R, Paxlovid®, Pfizer) negatively, 16% of patients were prescribed nirmatrelvir/ritonavir beyond five days of symptom onset, 4% of patients received N/R monotherapy within five days of symptom onset and 2% of patients received N/R combined with dexamethasone. Compared with untreated patients, N/R monotherapy reduced the median time to 10.0 days from 12.0 days according to the negative conversion of nucleic acid amplification test (NAAT), and combination therapy reduced the time to 7.0 days, and increased to a 1.99 (95% CI 0.92, 4.32) and 14.23-fold (95% CI 4.50, 44.95) probability of negative NAAT, respectively. N/R monotherapy reduced the clinical recovery time to 10.0 days from 13.0 days. Single-use and combined-use non-significantly increased the recovery probability by 61% and 69%, respectively. In mild and moderate patients, the HRs for clinical recovery increased to 1.69 (95% CI 0.73, 3.94) and 2.18 (95% CI 0.29, 16.62), respectively. Conclusion: Combination therapy of N/R and dexamethasone increased negative conversion of NAAT and was associated with a non-significant improvement in clinical recovery. Further studies are warranted to confirm this efficacy.

Prognostic prediction of the platelet-to-lymphocyte ratio in hepatocellular carcinoma: a systematic review and meta-analysis.

Background: Platelet-to-lymphocyte ratio (PLR) has been used to predict the prognosis of patients with hepatocellular carcinoma (HCC) with inconsistent results. This meta-analysis aimed to clarify the prognostic value of PLR in patients with HCC. Methods: We systematically retrieved relevant literature published in the PubMed, Embase, Web of Science, and Cochrane databases up to November 20, 2021. The primary outcomes were the hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival (OS), and secondary study outcomes were recurrence-free survival (RFS), disease-free survival (DFS), progression-free survival (PFS). All statistical analyses were conducted by Review Manager 5.4.1 and STATA 16.0 software. Results: A total of 21 studies comprising 8,779 patients were included in this meta-analysis. Pooled results suggested that a high PLR was significantly associated with poor OS (HR: 1.34, 95% CI: 1.18-1.52, P<0.00001; I2=59%, P=0.0005), RFS or DFS (HR: 1.35, 95% CI: 1.13-1.63, P=0.001; I2=69%, P=0.002), and PFS (HR: 1.55, 95% CI: 1.09-2.22, P=0.02; I2=73%, P=0.02). The subgroup analysis for OS showed, when the PLR cutoff value was greater than 150, the heterogeneity decreased to 0 (HR: 1.48, 95% CI: 1.33-1.68, P<0.00001; I2=0%, P=0.56); when the HBsAg positive population was increased to 100%, the heterogeneity decreased to 0 (HR: 1.46, 95% CI: 1.22-1.73, P<0.0001; I2=0%, P=0.45); compared with other regions in the world, it was more significant in China (HR: 1.43, 95% CI: 1.26-1.62, P<0.00001; I2=52%, P=0.01). In addition, scatter plot showed that the HR was negatively correlated with the proportion of patients with liver cirrhosis. Conclusions: This meta-analysis suggests that PLR is a negative correlation prognostic biomarker for HCC, high PLR values indicate poor OS, RFS, DFS and PFS, especially in hepatitis B virus (HBV) related patients.

Metformin Inducing the Change of Functional and Exhausted Phenotypic Tumor-Infiltrated Lymphocytes and the Correlation with JNK Signal Pathway in Triple-Negative Breast Cancer.

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Metformin has been shown to have the potential to inhibit the proliferation of malignant cells. This study aimed to investigate the regulatory effect of metformin on phenotypic tumor-infiltrated lymphocytes (TILs) and mechanisms in TNBC. Methods: Microarray analysis was performed on 4T1 cells post metformin treatment. BALB/c mice were inoculated with 4T1 cells with knockdown/overexpression of C-Jun N-terminal kinase (JNK), and administered with metformin. Phenotypic TILs in the tumor microenvironment (TME) were visualized by immunofluorescence staining. Results: Metformin inhibited 4T1 cell proliferation and increased expression of JNK by 21% in vitro. In vivo, Metformin increased cell counts of CD4+ and CD8+TILs by 100% and 85%, respectively, and the increase of TILs was associated with JNK pathway. Cell counts of CD4+/PD-1+ and CD8+/PD-1+TILs were reduced by 64% and 58%, respectively, post metformin treatment, but the reduction of exhausted TILs was not associated with JNK pathway. Metformin induced a 11% and 20% reduction of IL-6 and TNF-α level in the TNBC model. Conclusion: Our study demonstrated that metformin increased the functional phenotype of TILs and associated with JNK pathway, and suppressed the exhausted phenotype of TILs independently to JNK pathway in TNBC microenvironment. Further studies are needed to explore the basic mechanism of action of the drug. Metformin has potentially enhanced efficacy when used in combination with immunotherapy against TNBC.

Diagnostic Efficacy of CT Examination on Early Detection of Lung Cancer during Pandemic of COVID-19.

Background: Since the outbreak of COVID-19 in 2020, routine CT examination was recommended to hospitalized patients at some hospitals and discovered lung cancer patients at an early stage. This study aimed to investigate the detection efficacy of routine CT examination on early diagnosis of lung cancer, especially on pathological characteristics. Methods: The epidemic of COVID-19 outbreak in January 2020 in China, and routine CT examination was recommended to hospitalized patients in June 2020 and ended in July 2021. Based on the time points, we compared the diagnosis efficacy between three periods: pre-period, peri-period, and the period of routine CT examination. Results: During the period of routine CT examination, more early stages of lung cancer were detected and the tumor size was reduced to 2.14 cm from 3.21 cm at pre-period (p = 0.03). The proportion of lung adenocarcinoma and early stage adenocarcinoma was increased by 12% and 30% in the period of routine CT examination, with referral to the pre-period of CT examination (p < 0.05). A total of 61% of diagnosed patients had the wild type of TP53 gene during the period of routine CT examination, compared to 45% of patients at the pre-period of CT examination (p = 0.001). The median Ki-67 index was 15% among patients diagnosed at the period of routine CT examination and increased to 35% at the pre-period of CT examination (p < 0.001). The period of routine CT examination was associated with a 78% higher probability of detecting an early stage of adenocarcinoma (OR = 1.78, 95%CI 1.03, 3.08) but no significant association was observed for squamous cell carcinoma. From the pre-period to the period of routine CT examination, the proportion of female patients and non-smoking patients increased by 57% and 44%, respectively (p < 0.001). Conclusion: Routine CT examination could detect more lung cancer at an early stage, especially for adenocarcinoma, and detect patients with less aggressive features. Further studies were warranted to confirm the findings.

High Serum Squamous Cell Carcinoma Antigen Level Associated with Remission of Mild/Moderate Dysplasia of the Esophagus: A Nested Case-Control Study.

Background: The esophageal epithelial dysplasia is the precancerous lesion. This study aimed to investigate the association between the serum squamous cell carcinoma antigen (SCCA) and the remission of esophageal squamous mild or moderate dysplasia. Methods: We performed a nested case-control study. Patients with mild/moderate dysplasia of the esophageal squamous epithelium were enrolled in this study during the years of 2013-2015 and received a follow-up endoscopy during 2017-2018. With the comparison between baseline and follow-up diagnosis, the patients were divided into regression/stable and progression groups. A predictive model for the outcome of dysplasia was comprised of the variables of SCCA, age, sex, education level, and baseline dysplasia grade. A receiver operating characteristic (ROC) curve was used to estimate the diagnostic efficacy of the regression status of dysplasia under the predictive model. Results: There were 146 patients enrolled in this study. 100 patients experienced a regression or stable status of dysplasia and 46 patients had a progressed status. Increased age, low education level, and moderate dysplasia were the risk factors of progression. With an 0.1 µg/L increase, SCCA was associated with a 0.90-fold risk (95% CI 0.81, 0.99) of progression. In the predictive model, the area under ROC curve was 0.78. The cut-off values of predictive probability of combined factors for progression, were 0.40 and 0.32 for males and females, respectively. Conclusions: Increased serum SCCA concentration was associated with regressed severity of mild and moderate dysplasia of the esophageal mucosa. Further studies were warranted and SCCA concentration was a potential biomarker for the dysplasia prognosis.

Consistent expression of PD-L1 in tumor microenvironment with peripheral PD-1/PD-L1 in circulating T lymphocytes of operable breast cancer: a diagnostic test.

BACKGROUND: The expression of PD-L1 in the immune microenvironment can guide the application of immunosuppressants. In order to monitor the immune status of the body, repeated biopsies have to be taken. Our research aims to find new and convenient means to evaluate this indicator. METHODS: Eighty-three cases of newly diagnosed operable breast cancer without receiving preoperative treatment, were recruited from Beijing Shijitan Hospital between November 2018 and November 2019. The expression of PD-1/PD-L1 on circulating T lymphocytes was detected by flow cytometry and the expression of PD-L1 on immune cells in tumor microenvironment was detected by immunohistochemistry. RESULTS: The median percentage of positive PD-1 and PD-L1 expression on circulating T lymphocytes was 15.2% and 0.7%, respectively. The peripheral PD-1 had no relationship with clinicopathological characteristics, but the peripheral PD-L1 expression had a correlation with lymph node metastasis (p = 0.005) and Her-2 expression (p = 0.034) (p < 0.05). The positive rate of PD-L1 expression was 32.9% in tumor microenvironment. PD-L1 expression in tumor microenvironment had a significant correlation with PD-1/PD-L1 expression on circulating T lymphocytes, the correlation coefficients being 0.24 (p < 0.05) and 0.26 (p < 0.05), respectively. To predict the PD-L1 expression in tumor microenvironment, the area under the receiver operating characteristic curve was 0.65 and 0.66 for peripheral PD-1 and PD-L1, respectively. High level of peripheral PD-1/PD-L1 expression was associated with the odds ratios of 5.42 and 4.76 for positive PD-L1 expression in tumor microenvironment. CONCLUSION: Peripheral PD-1/PD-L1 expression had a significant consistency with PD-L1 expression in tumor microenvironment and could act as an alternative choice of tissue detection, for the patients intolerable of biopsy.

Correlation between hepatic venous pressure gradient and portal venous pressure gradient in hepatitis B cirrhosis with different hepatic veins anatomy.

PURPOSE: The hepatic venous pressure gradient (HVPG) has been employed as the gold standard for indicating the portal venous pressure gradient (PPG) in the diagnosis of portal hypertension (PHT). However, little has been reported on whether the HVPG can accurately estimate the PPG in patients with hepatic vein collateral shunts. We aimed to explore the correlation between the HVPG and the PPG in hepatitis B cirrhosis patients with different hepatic vein anatomies. METHODS: A total of 461 hepatitis B cirrhosis patients with portal hypertension (PHT) who were treated with a transjugular intrahepatic portosystemic shunt (TIPS) between January 2016 and June 2020 were included. All patients underwent various venous pressure measurements and balloon-occluded compression hepatic venography during the TIPS operation. Agreements were evaluated by Pearson's correlation and the Bland-Altman method. Disagreements were assessed by paired t tests. RESULTS: The correlation coefficient (r) values (P < 0.001) between the HVPG and the PPG of the early (151 patients, 32.8 %), middle (73 patients, 15.8 %), late (46 patients, 10.0 %), portal vein (151 patients, 32.8 %), and no lateral branch development groups (40 patients, 8.7 %) were 0.373, 0.487, 0.569, 0.690, and 0.575, respectively; the determination coefficient (R2) values were 0.139, 0.238, 0.323, 0.475, and 0.330, respectively. According to the Bland-Altman method, agreement was the greatest in the portal vein development group, with the 95 % limits of agreement (95 % LoA, mean differences ± 1.96 SD) being the smallest. The differences were statistically significant (P < 0.05). CONCLUSION: The correlation between the HVPG and the PPG is the worst in early lateral branch development, followed by middle development, and the influence of lateral branches becomes significantly reduced in late development. Hepatic venous collateral formation is a vital factor for underestimation of the HVPG, which is the most accurate predictor of PPG in patients with portal vein development. Patients with no collateral channel development in the hepatic vein have a higher HVPG than PPG, which is an important reason for overestimation of the HVPG.

Metformin With or Without Clomiphene Citrate Versus Laparoscopic Ovarian Drilling With or Without Clomiphene Citrate to Treat Patients With Clomiphene Citrate-Resistant Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

Introduction: Which is optimal to treat clomiphene citrate-resistant polycystic ovary syndrome (CCR-PCOS) with LOD or metformin remains a problem. There are three inconsistent or even contradictory views. Objectives: The present meta-analysis aimed to evaluate the effectiveness and safety of Metformin with or without CC and to compare them with LOD with or without CC (Met/Met-CC vs. LOD/LOD-CC) in women with CCR-PCOS who also have anovulation. Data source: The PubMed, Cochrane, and Embase databases were searched to identify relevant studies reported between 1 Jan 1966 and 31 Aug 2019; the search was updated on 17 May 2022. Study eligibility criteria: We included randomized controlled trials (RCTs) of CCR-PCOS that had considered Met/Met-CC and LOD/LOD-CC as the exposure variables and fertility as the main outcome variable. Study appraisal and synthesis methods: We assessed study quality using the Cochrane risk-of-bias tool. The primary effectiveness outcome was live birth/ongoing pregnancy rate and the primary safety outcome was miscarriage rate. A fixed-effect meta-analysis was performed. The robustness of the results was assessed using sensitivity analyses. Meta-regression and subgroup analysis were performed to examine the reasons for heterogeneity. Publication bias was examined using the funnel plot, Egger linear regression, and Begg rank correlation tests. The quality of this meta-analysis was estimated according to the GRADE approach. This meta-analysis has been registered in PROSPERO (CRD42021240156). Results: Among 71 potentially relevant studies, we included five RCTs in our meta-analysis. We found no difference in effectiveness between Met-CC and LOD in terms of live birth/ongoing pregnancy (RR = 1.02, 95% CI: 0.87-1.21, z = 0.28; p = 0.780), and miscarriage rates (RR = 0.79, 95% CI: 0.46-1.36, z = 0.86; p = 0.390). I2 tests results revealed moderate or no heterogeneity (I2 = 51.4%, p = 0.083; I2= 0.0%; p = 0.952). Sensitivity analysis confirmed the robustness of the results. Funnel plot, Egger linear regression, and Begg rank correlation tests implied no publication bias (p > 0.05). LOD was more expensive than Met (€1050 vs. €50.16). The evidence quality was moderate. Conclusion: There is no evidence on the difference in the outcomes between the two interventions regarding ovulation, pregnancy, and live birth. As LOD is an invasive procedure and carries inherent risks, the use of Met/Met-CC should be the second-line treatment for women with CCR-PCOS. Systematic Review Registration: identifier CRD42021240156.

Correlation of pressure gradient in three hepatic veins with portal pressure gradient.

BACKGROUND: The liver is one of the most important organs in the human body, with functions such as detoxification, digestion, and blood coagulation. In terms of vascular anatomy, the liver is divided into the left and the right liver by the main portal vein, and there are three hepatic efferent veins (right, middle, and left) and two portal branches. Patients with impaired liver function have increased intrahepatic vascular resistance and splanchnic vasodilation, which may lead to an increase in the portal pressure gradient (PPG) and cause portal hypertension (PHT). In order to measure the increased pressure gradient of portal vein, the hepatic venous pressure gradient (HVPG) can be measured to reflect it in clinical practice. The accuracy of PPG measurements is directly related to patient prognosis. AIM: To analyze the correlation between HVPG of three hepatic veins and PPG in patients with PHT. METHODS: From January 2017 to December 2019, 102 patients with PHT who met the inclusion criteria were evaluated during the transjugular intrahepatic portosystemic shunt procedure and analyzed. RESULTS: The mean HVPG of the middle hepatic vein was 17.47 ± 10.25 mmHg, and the mean HVPG of the right and left hepatic veins was 16.34 ± 7.60 and 16.52 ± 8.15 mmHg, respectively. The average PPG was 26.03 ± 9.24 mmHg. The correlation coefficient and coefficient of determination of the right hepatic vein, middle hepatic vein, and left hepatic vein were 0.15 and 0.02 (P = 0.164); 0.25 and 0.05 (P = 0.013); and 0.14 and 0.02 (P = 0.013), respectively. The mean wedged hepatic vein/venous pressure (WHVP) of the middle and left hepatic veins was similar at 29.71 ± 12.48 and 29.1 ± 10.91 mmHg, respectively, and the mean WHVP of the right hepatic vein was slightly lower at 28.01 ± 8.95 mmHg. The mean portal vein pressure was 34.11 ± 8.56 mmHg. The correlation coefficient and coefficient of determination of the right hepatic vein, middle hepatic vein, and left hepatic vein were 0.26 and 0.07 (P = 0.009); 0.38 and 0.15 (P < 0.001); and 0.26 and 0.07 (P = 0.008), respectively. The average free hepatic venous pressure (FHVP) of the right hepatic vein was lowest at 11.67 ± 5.34 mmHg, and the average FHVP of the middle and left hepatic veins was slightly higher at 12.19 ± 4.88 and 11.67 ± 5.34 mmHg, respectively. The average inferior vena cava pressure was 8.27 ± 4.04 mmHg. The correlation coefficient and coefficient of determination of the right hepatic vein, middle hepatic vein, and left hepatic vein were 0.30 and 0.09 (P = 0.002); 0.18 and 0.03 (P = 0.078); and 0.16 and 0.03 (P = 0.111), respectively. CONCLUSION: Measurement of the middle hepatic vein HVPG could better represent PPG. Considering the high success rate of clinical measurement of the right hepatic vein, it can be the second choice.

Risk factors of pleural effusion after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in late-stage and recurrent ovarian cancer.

BACKGROUND: Pleural effusion (PE) is one of the most common complications of advanced recurrent ovarian cancer. However, no studies have revealed the risk factors for PE after surgery. The purpose of this study is to observe the incidence and risk factors of PE after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with late-stage and recurrent ovarian cancer. METHODS: A retrospective analysis of 77 patients with late-stage and recurrent ovarian cancer after CRS + HIPEC was conducted. According to the presence of PE within 7 days after operation, two groups were formed. The basic information, surgical process, and laboratory examinations of the two groups were analyzed and compared to conduct a regression analysis. RESULTS: The incidence of postoperative PE was 57.1% (44/77 patients). Among these patients, the prevalence of grade I-II and grade III-IV PE was 42.8% (33/77 patients) and 14.3% (11/77 patients), respectively. There were statistically significant differences between the two groups in terms of preoperative PE, the duration of surgery, intraoperative blood loss, postoperative level of albumin, intestinal involvement, and diaphragmatic involvement. Among these, preoperative PE and diaphragmatic involvement were identified as independent risk factors of postoperative PE. CONCLUSIONS: Patients with late-stage and recurrent ovarian cancer invariably develop postoperative PE after CRS + HIPEC. Preoperative PE and diaphragmatic involvement are independent risk factors of postoperative PE. It is estimated that the incidence of postoperative PE among patients with these two independent risk factors is approximately 100%. Hence, we should promote the prevention and treatment of PE to improve its prognosis.

A Survey Study Reveals the Positive Impact of Oncofertility Knowledge and Attitude on Oncofertility Practice Among Oncologists in China.

Purpose: The advances of early cancer diagnoses and treatment methods allow many adolescent and young adult-aged cancer patients to live long lives after having cancer. There is a rising concern regarding cancer treatment-induced reproductive toxicities and infertility. Oncologists are the first line of medical professionals interacting with cancer patients and playing essential roles in oncofertility practice. This study aimed to assess the oncofertility knowledge, attitude, and practice of oncologists in China. Methods: We created an online questionnaire survey to examine 927 Chinese oncologists' demographics, knowledge, attitude, experience, and practice regarding young female cancer patients' infertility risk and fertility preservation. Results: Results showed that there is an inadequate oncofertility knowledge among surveyed oncologists, which was affected by oncologists' demographic background of education level, clinical title, and working experience. The majority of surveyed oncologists (84.8%-88.7%) held a positive attitude on young female cancer patients' infertility risk and their fertility preservation demand, but their attitude was impacted by marriage status and patients risk of cancer recurrence. Only 11.8% of surveyed oncologists often referred their patients for fertility preservation, while 66.3% and 21.9% of them have referred once or never, respectively. The oncologists' oncofertility practice was not correlated with their demographic background but was significantly influenced by their oncofertility knowledge and attitude. Conclusion: Our study demonstrates that there is an urgent unmet need to improve oncologists' oncofertility knowledge, attitude, and practice in China as well as remove the communication barrier between oncologists and fertility specialists.

The integration of proportion and cell counts of stromal, not intratumoral, PD-1+ tumor-infiltrating lymphocytes has prognostic significance in esophageal squamous cell carcinoma.

The present study aimed to investigate the prognostic effect of intratumoral and stromal exhausted tumor-infiltrating lymphocytes (TILs) on operable esophageal cancer patients. We performed a retrospective cohort study by consecutively recruiting 142 patients with esophageal cancer. The proportion and cell counts of intratumoral and stromal PD-1+ TILs in tumor microenvironment were independently evaluated by two pathologists. Neither proportion nor cell counts of intratumoral PD-1+ TILs was associated with prognosis (p > 0.05). However, patients with the proportion of stromal PD1+ TILs >20% had the median overall survival (OS) at 19 months, significantly longer than those with the proportion = 20%. The adjusted hazard ratio (HR) was 1.49 (95%CI 0.82, 2.69). Patients with cell counts of stromal PD1+ TILs = 18/ high-power field (HPF) had the median disease-free survival (DFS) at 10 months. However, patients with cell counts>18/HPF had the median DFS at 48 months (p = 0.037), and the adjusted HR was 0.59 (95%CI 0.35, 1.01). Compared with patients with proportion = 20% and cell counts >18/HPF of stromal PD1+ TILs, patients with proportion = 20% and cell counts = 18/HPF, proportion >20% and cell counts >18/HPF, and proportion >20% and cell counts = 18/HPF, had the adjusted HRs increased to 3.73, 3.36 and 3.99 for DFS (p for trend being 0.030) and the adjusted HRs increased to 2.95, 3.64 and 3.82 (p for trend being 0.015) for OS, respectively. The integration of proportion and cell counts of PD-1+ stromal TILs has a significant association with the relapse and overall survival of esophageal cancer patients. Further prospective studies are warranted.

The motivations, barriers, and sociodemographic characteristics of healthy Chinese volunteers in phase I research.

PURPOSE: To describe the motivations, barriers, and sociodemographic characteristics of healthy Chinese volunteers in phase I research and to demonstrate the factors influencing their willingness to participate in subsequent trials. METHODS: Healthy subjects who participated in seven phase I trials at two centres were invited to participate in the cross-sectional survey at discharge by anonymously and voluntarily completing the self-administered questionnaire. RESULTS: From 442 subjects asked to complete the questionnaire, a response rate of 94.8% (419) was obtained, and 72.8% of the respondents had participated in a mean of 2.0 ± 1.3 previous studies. Over 90% of the subjects indicated that the main motivations to participate trials were to help more people, to contribute to scientific research, and to obtain money. The top 5 barriers were time inconvenience, advertisement sources, potential risks associated with the drug, privacy, and the route of drug administration. Nearly half (49.6%) of the subjects were willing to participate in the next trial. The factors impacting the willingness of the subjects to participate in subsequent trials were gender, screening frequency, enrolment frequency, level of understanding of the research, two motivating factors (to make money and receive a free check-up), and ten barriers (e.g. risk, distance, living conditions, and trust). CONCLUSIONS: The majority of healthy Chinese subjects were young, were less well educated, had low income levels, and had poor medical insurance coverage. Given the multiple sources of motivation and complex barriers to trial participation, investigators and recruitment staff should consider ethics aspects to guarantee volunteer safety and well-being.

Overexpression of CD155 is associated with PD-1 and PD-L1 expression on immune cells, rather than tumor cells in the breast cancer microenvironment.

BACKGROUND: CD155 is an immune checkpoint protein in cancers and interacts with ligands to regulate the immune microenvironment. The expression of CD155 is correlated with the prognosis and pathological features of breast cancer. AIM: To investigate the expression status of CD155 and the association with exhausted CD4+ helper and CD8+ cytotoxic tumor infiltrating lymphocytes (TILs) and PD-L1 in the breast cancer microenvironment. METHODS: One hundred and twenty-six breast cancer patients with invasive ductal breast cancer were consecutively recruited into this study. Immunohistochemistry was used to detect the expression CD155, PD-L1 and PD-1 on tumor-infiltrating immune cells and tumor cells in the microenvironment. RESULTS: The proportion of patients with CD155 expression was higher in triple negative breast cancer (72.7%) than in Luminal A patients (22.2%, P < 0.05). Patients with positive CD155 expression had a higher percentage of CD4+/PD-1+ helper TILs (30%) than patients with negative CD155 expression (21%, P < 0.05). Patients with positive CD155 expression also had higher cell counts of exhausted CD4+ TILs [47 vs 20/high-power fields (HPF)] and unexhausted CD8+ TILs (30 vs 17/HPF) than patients with negative expression (P < 0.05). CD155 expression was correlated with increased PD-L1 expression in immune cells, 0.8% and 0.02% immune cells expressed PD-L1 in patients with positive and negative CD155 expression, respectively (P < 0.05). CONCLUSION: CD155 was related to an inhibitory immune breast cancer microenvironment. CD155 was associated with a high proportion of exhausted CD4+ and unexhausted CD8+ TILs and high PD-L1 expression in immune cells.

Prognostic significance of PD-L1 in advanced non-small cell lung carcinoma.

This study aimed to investigate the prognostic value of PD-L1 in Chinese patients with non-small cell lung carcinoma (NSCLC).In this retrospective study, 97 patients with NSCLC were consecutively recruited. The expression profiling of PD-1, PD-L1, p53 and Ki-67 was detected by immunohistochemistry. Median survival time was estimated by Kaplan-Meier survival curve with log-rank test. Risk factors were evaluated by Cox Proportional Hazards regression models.The median tumor size was larger (3.5 cm) among patients with positive PD-L1 expression, compared to those with negative expression (2.0 cm; P < .01). Compared to those with negative PD-L1 expression, patients with positive PD-L1 expression had significantly higher rates of nerve invasion (26.3% vs 5.0%; P < .01), blood vessel invasion (47.4% vs 20.0%; P < .01) and lymph node metastasis (64.9% vs 27.5%; P < .01), more advanced tumor stage (P < .01) and Ki-67 index (P < .01). PD-L1 expression status was not significantly associated with disease-free (DFS) or overall survival (OS). However, for patients with advanced disease, PD-L1 positive expression was related to worse outcome (HR: 4.13; 95% CI: 1.06-16.12).Positive PD-L1 expression is associated with more aggressive pathological features and poorer prognosis in advanced stage NSCLC.

Evaluation of Factors Associated with Anxiety and Depression in Chinese Visiting Scholars in the United States During the COVID-19 Pandemic Assessed by Online Questionnaires.

BACKGROUND This study aimed to use online questionnaires to evaluate the factors associated with anxiety and depression in Chinese visiting scholars in the United States during the COVID-19 pandemic. MATERIAL AND METHODS Using a cross-sectional design, 311 Chinese scholars visiting 41 states in the United States were interviewed on 20 and 21 April 2020 through WeChat using the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7) questionnaire. RESULTS Of these 311 visiting scholars, 69 (22.2%) reported no symptoms of anxiety or depression, whereas 63 (20.3%) reported severe anxiety and 67 (21.5%) reported severe depression. Risk of anxiety was 93% higher in visiting scholars with than without accompanying parents in the US (odds ratio [OR], 1.93; 95% confidence interval [CI], 1.01-3.68) and was 1.72-fold (95% CI, 1.04-2.84) higher in those experiencing stress about family members with COVID-19. Stresses about personal security and return to China on schedule were associated with 1.73-fold (95% CI, 1.03-2.92) and 3.00-fold (95% CI, 1.51-5.95) higher risks of anxiety, respectively. Risks of depression were 1.86-fold (95% CI, 1.14-3.05), 1.84-fold (95% CI, 1.10-3.07), and 3.45-fold (95% CI, 1.72-6.92) higher in visiting Chinese scholars who were than were not experiencing stresses about financial support, personal security and return to China on schedule, respectively. CONCLUSIONS Chinese scholars visiting the United States during the COVID-19 pandemic experienced severe psychological distress. Surveys that include larger numbers of visiting scholars are warranted.

Interactive Effects of PD-L1 Expression in Tumor and Immune Cells on Prognosis of Esophageal Squamous Cell Carcinoma: A One-Center Retrospective Cohort Study.

PURPOSE: The present study aimed to investigate the prognostic effect of PD-L1 expressing in tumor and immune cells among patients with esophageal squamous cell carcinoma. PATIENTS AND METHODS: We performed a retrospective cohort study by consecutively recruiting 142 patients. The clinicopathological features and PD-L1 expression on tumor and immune cells were independently evaluated by two pathologists. RESULTS: The median expression rate of PD-L1 was 5% and 30% in tumor and immune cells, respectively. Patients with higher expression of PD-L1 in tumor cells had shorter disease-free and overall survival, and the HRs were 1.52 for relapse (95% CI: 0.88, 2.60) and 1.48 for death (95% CI: 0.82, 2.69). There was no significant association between the PD-L1 expression in immune cells and survival. However, among the patients with PD-L1 expression rate ≤30% in immune cells, the high expression rate of PD-L1 in tumor cells was significantly associated with the relapse and death, with HRs of 2.51 (95% CI: 1.25, 5.06) and 3.51 (95% CI: 1.57, 7.85), respectively. Among patients with PD-L1 expression rate >30% in immune cells, the PD-L1 expression in tumor cells did not show any association with the disease-free and overall survival. CONCLUSION: Our study demonstrates that the integration of PD-L1 expression in tumor and immune cells could be used to predict the relapse and survival among patients with esophageal squamous cell carcinoma.