Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

BACKGROUND: Although intensively studied in patients with cardiovascular diseases (CVDs), the prognostic value of diastolic blood pressure (DBP) has little been elucidated in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study aimed to reveal the prognostic value of DBP in AECOPD patients. METHODS: Inpatients with AECOPD were prospectively enrolled from 10 medical centers in China between September 2017 and July 2021. DBP was measured on admission. The primary outcome was all-cause in-hospital mortality; invasive mechanical ventilation and intensive care unit (ICU) admission were secondary outcomes. Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regressions were used to identify independent prognostic factors and calculate the hazard ratio (HR) and 95% confidence interval (CI) for adverse outcomes. RESULTS: Among 13,633 included patients with AECOPD, 197 (1.45%) died during their hospital stay. Multivariable Cox regression analysis showed that low DBP on admission (<70 mmHg) was associated with increased risk of in-hospital mortality (HR = 2.16, 95% CI: 1.53-3.05, Z = 4.37, P <0.01), invasive mechanical ventilation (HR = 1.65, 95% CI: 1.32-2.05, Z = 19.67, P <0.01), and ICU admission (HR = 1.45, 95% CI: 1.24-1.69, Z = 22.08, P <0.01) in the overall cohort. Similar findings were observed in subgroups with or without CVDs, except for invasive mechanical ventilation in the subgroup with CVDs. When DBP was further categorized in 5-mmHg increments from <50 mmHg to ≥100 mmHg, and 75 to <80 mmHg was taken as reference, HRs for in-hospital mortality increased almost linearly with decreased DBP in the overall cohort and subgroups of patients with CVDs; higher DBP was not associated with the risk of in-hospital mortality. CONCLUSION: Low on-admission DBP, particularly <70 mmHg, was associated with an increased risk of adverse outcomes among inpatients with AECOPD, with or without CVDs, which may serve as a convenient predictor of poor prognosis in these patients. CLINICAL TRIAL REGISTRATION Chinese Clinical Trail Registry, No. ChiCTR2100044625.
Humans ; Blood Pressure ; Pulmonary Disease, Chronic Obstructive/therapy* ; Cohort Studies ; Respiration, Artificial ; Inpatients ; Hospital Mortality

Closed-loop hospital management can effectivly cope with the COVID-19 pandemic. In order to ensure the continuity of treatments for hemodialysis patients under closed-loop management and minimize possible medical and infection risks, Huashan Hospital affiliated to Fudan University and 9 hospitals in Shanghai established a hemodialysis alliance in January 2021.The alliance optimized hemodialysis resources within the region through overall planning by preparing sites, materials and personnel shifts in advance, and establishing management systems and work processes to ensure that patients could be quickly and orderly diverted to other blood dialysis centers for uninterrupted high-quality hemodialysis services, in case that some hemodialysis centers in the alliance under closed-loop management.From November 2021 to April 2022, 317 of 1 459 hemodialysis patients in the alliance were diverted to other centers for treatment, accumulating 1 215 times/cases of treatments without obvious adverse reactions. The practice could provide a reference for medical institutions to quickly establish mutual support mode under major public health events.

Postzygotic mutations are acquired in normal tissues throughout an individual's lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clock-like mutational processes,and the polymorphisms of epigenetic regulation genes influence the pro-portion of signature B in mutation profiles.Notably,signature C,characterized by C＞T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6％of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C＞T transitions at GpCpN sites;and indi-viduals'genetic background may also influence their postzygotic mutation profiles.

Objective:To investigate whether it is by regulating interleukin 1β ( IL-1β) gene expression that androgen receptor (AR) in macrophages affects hyperphosphate-induced vascular smooth muscle cell calcification. Methods:The chromatin immunoprecipitation (ChIP) experiment was used to determine whether AR was bound to the androgen receptor element (ARE) sequence of IL-1β promoter in THP-1 cells. Whether the AR regulated IL-1β gene expression was detected by luciferase assay experiments. AR of THP-1 cells was silenced and transfected by lentivirus with vector or shRNA. Flow cytometry was used to select positive transfected cells THP-1ARsc (control) and THP-1ARsi (AR silencing) with fluorescent markers. Western blotting was used to detect AR protein levels of THP-1ARsc (control) and THP-1ARsi cells (AR silencing in monocytes). Macrophages MФARsc (control) or MФARsi (AR silencing) were induced by 50 ng/ml phorbol ester. Enzyme-linked immunosorbent assay was used to detect IL-1β expression levels of MФARsc or MФARsi conditioned medium. The human aortic smooth muscle cells (HASMC) were cultured in MФARsc or MФARsi conditioned medium with phosphate (2.5 mmol/L final concentration of sodium dihydrogen phosphate), and Alizarin red S staining was used to analyze HASMC calcification degree. Western blotting was used to detect the expression levels of RUNX2 (osteoblast marker) and SM22α (HASMC marker), and neutralization assay was performed to test IL-1β-mediating effect of macrophages AR on HASMC calcification. Results:AR was bound to ARE sequence of IL-1β promoter and regulated IL-1β gene expression. The expression level of IL-1β protein in conditioned medium of MФARsi cells decreased significantly compared to MФARsc cells ( P<0.001). Compared with MФARsc conditioned medium group, HASMC calcium deposition in MФARsi conditioned medium group decreased significantly, RUNX2 protein decreased and SM22α protein increased (all P<0.05). The degree of HASMC calcification in the MФARsi conditioned medium+IgG antibody group decreased than that in the MФARsc conditioned medium+IgG antibody group significantly, and the degree of HASMC calcification in the MФARsc conditioned medium+IL-1β antibody group decreased significantly than that in the MФARsc conditioned medium+IgG antibody group; while the degree of HASMC calcification in the MФARsi conditioned medium+IgG antibody group and MФARsi conditioned medium+IL-1β antibody group decreased than that in the MФARsc conditioned medium+IL-1β antibody group (all P<0.05). Conclusions:Macrophage AR regulates IL-1β expression by binding to ARE sequence within IL-1β promoter, and IL-1β mediates the effect of macrophage AR on hyperphosphate-induced HASMC calcification.

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

Objective:To systematically evaluate the predictive value of neutrophil-lymphocyte ratio (NLR) in acute kidney injury (AKI).Methods:All studies about the predictive effect of NLR on AKI were searched in the National Medical Library of the United States PubMed Database, the Embase database in the Netherlands, the Chinese Biology Medicine disc (CBMdisc) and the Chinese Evidence Based Medicine Cochrane Centre Database (CEBM/CCD). The data updated by October 2020, and regardless of language, region or whether blind method was used. Two authors independently extracted data and evaluated the quality of the studies. Data extracted from the studies were analyzed with RevMan 5.3 to assess the predictive value of NLR on AKI. A subgroup Meta-analysis was conducted to assess the predictive value of NLR on AKI according to different countries, different disease types (cardiovascular surgery, infectious diseases, other diseases including burns, cirrhosis, and emergency), and different sample sizes (≤ 300 cases and > 300 cases). The publication bias of included studies about the predictive effect of NLR on AKI were assessed by funnel plots.Results:A total of 11 studies were included in this Meta-analysis, including 4 997 patients, 1 308 patients in AKI group, and 3 689 patients in non-AKI group. The Meta-analysis results showed that: increased NLR had predictive value for the occurrence of AKI [mean difference ( MD) = 2.73, 95% confidence interval (95% CI) was 1.78-3.68, P < 0.000 01]. Subgroup analysis showed that increased NLR had predictive value for the occurrence of AKI in patients from Southeast Asia ( MD = 4.04, 95% CI was 1.09-6.99, P = 0.007) and Eurasia ( MD = 2.51, 95% CI was 1.12-3.90, P = 0.000 4). Increased NLR had predictive value for the occurrence of AKI in patients undergoing cardiovascular surgery ( MD = 0.77, 95% CI was 0.34-1.20, P = 0.000 4), infectious diseases ( MD = 4.74, 95% CI was 1.51-7.96, P = 0.004) and other diseases ( MD = 8.53, 95% CI was 6.26-10.80, P<0.000 01). Increased NLR had predictive value for the occurrence of AKI in studies with a sample size of ≤ 300 cases ( MD = 6.02, 95% CI was 4.90-7.14, P <0.000 01) and > 300 cases ( MD = 1.32, 95% CI was 0.61-2.03, P = 0.000 3). There was no significant publication bias in the included studies assessed by funnel plots. Conclusion:NLR is an important predictive tool for AKI.

Objective:To study the effects of cisapride on digestive symptoms and gastrointestinal hormones in elderly peritoneal dialysis patients.Methods:Forty-two elderly patients with renal failure undergoing peritoneal dialysis in our hospital from July 2017 to December 2017 were randomly selected as the study group.Meanwhile, 20 healthy elderly people in the corresponding time period were selected as the control group.Control group received continuous ambulatory peritoneal dialysis(CAPD)and other conventional basic therapy, and study group received cisapride as add-on therapy to treatment for control group.Serum levels of somatostatin(SS), motilin(MOT)and vasoactive intestinal peptide(VIP)were compared between the two groups.Gastrointestinal symptoms, serum levels of gastrointestinal hormones and biochemical indexes were compared before and after treatment in the study group.Results:The score of acid reflux, nausea, abdominal distension, belching and constipation were lower in the study group after treatment than before treatment( t=4.42, 4.32, 6.80, 6.29 and 6.76, all P=0.00). Before treatment, levels of MOT, SS and VIP were higher in the study group than in the control group[(636.65±32.02)pmol/L vs.(228.47±28.74)pmol/L, (64.02±16.32)mg/L vs.(42.38±6.42)mg/L, (118.64±17.68)ng/L vs.(58.62±11.63)ng/L, t=48.44, 7.47 and 15.93, all P=0.00]. The level of MOT was lower after than before treatment[(385.36±19.64)pmol/L vs.(636.65±32.02)pmol/L, t=43.36, P=0.00], and the levels of SS and VIP had no significant difference before versus after treatment( t=-0.11 and -0.42, P=0.91 and 0.68). After treatment, the level of MOT was still higher in the study group than in the control group[(385.36 ±19.64)pmol/L vs.(228.47 ±28.74)pmol/L, t=22.08, P=0.00]. There was no significant difference in blood urea nitrogen(BUN), creatinine, haemoglobin and kt/v levels between before and after treatment( P>0.05). The level of albumin(ALB)was higher after than before treatment[(38.60±1.89)g/L vs.(37.71±1.96)g/L, t=2.12, P=0.04]. Conclusions:Gastrointestinal symptoms are common in elderly patients with peritoneal dialysis, and the accumulation of gastrointestinal hormones is obvious, which leads to gastrointestinal dysfunction.The conventional treatment in combination with cisapride can improve gastrointestinal symptoms and reduce serum MOT level in these patients.

Objective:To investigate the effects of abdominal aortic calcification (AAC) progression on outcomes in maintenance hemodialysis (MHD) patients.Methods:Patients who were on MHD between Jun. 2014 and Oct. 2014 in the dialysis center of the Second Hospital of Tianjin Medical University and finished the AAC examination at baseline and two years later were included prospectively. The progression of AAC by AAC score (AACs) at baseline and two years later was evaluated. According to the change of AACs, the patients were divided into rapid AAC progression group and non-rapid AAC progression group. The effect of AAC progression on outcomes in MHD patients in the follow-up period was investigated. Kaplan-Meier analysis was used to compare their survival rates. Multivariable Cox regression model was used to determine the risk factors of all-cause mortality, cardiovascular mortality and cardiovascular events.Results:A total of 111 MHD patients were included, including 51 males and 60 females, aged (52.24±12.69) years. Baseline AAC prevalence was 45.9% (51/111), and median AACs was 0 (0, 5); After 2 years, the prevalence of AAC was 78.4% (87/111), and the median AACs was 6 (2, 11). There were 54 cases in the AAC rapid progression group (AACs change value>2) and 57 cases in the non-rapid AAC progression group (AACs change value≤2). The median follow-up duration was 27.9(27.1, 28.0) months. Kaplan-Meier analysis showed that patients in rapid AAC progression group had a higher risk of mortality as compared to patients in non-rapid AAC progression group (Log-rank χ2=5.695, P=0.017). Multivariate Cox regression analysis demonstrated that high baseline AACs ( HR=1.135, 95% CI 1.001-1.286, P=0.048), hypoalbuminemia ( HR=0.789, 95% CI 0.640-0.972, P=0.026) were independent risk factors for all-cause mortality in MHD patients. High baseline AACs ( HR=1.187, 95% CI 1.038-1.356, P=0.012), low spKt/V ( HR=0.103, 95% CI 0.013-0.801, P=0.030) were independent risk factors for cardiovascular mortality in MHD patients. Low spKt/V ( HR=0.018, 95% CI 0.003-0.115, P<0.001), hypoalbuminemia ( HR=0.736, 95% CI 0.608-0.890, P=0.002) were independent risk factors for cardiovascular events in MHD patients. Conclusions:Abdominal aortic calcification progression may increase the risk of cardiovascular events and death in MHD patients. Severity of AAC, adequacy of dialysis, and nutritional status are predictors of outcomes in MHD patients.

Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5-10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.