Objective:To analyze the efficacy of laparoscopic radical surgery, compared to open surgery, for incidental gallbladder cancer following cholecystectomy.Methods:Clinical data of 106 patients with incidental gallbladder cancer treated at the Second Affiliated Hospital Zhejiang University School of Medicine from April 2010 to February 2018 were retrospectively analyzed, including 66 males and 40 females, aged (64.7±7.9) years old. According to surgical approach, patients were divided into the laparoscopic group ( n=45) and open group ( n=61). Perioperative data, including intraoperative blood loss, postoperative hospital stay, and postoperative complications, were compared between the groups. Follow-ups were conducted via outpatient visits or telephone reviews. Survival analysis was performed using the Kaplan-Meier method, and the survival rates were compared using the log-rank test. Results:All 45 patients in the laparoscopic group successfully underwent the surgery without conversion to open surgery. Compared to the open group, the laparoscopic group had a reduced intraoperative blood loss [(100±25) ml vs. (200±46) ml] and a shortened postoperative hospital stay [3(2, 5) d vs. 5(4, 7) d] (both P<0.05). The postoperative complication rates were 6.7% (3/45) in the laparoscopic group and 13.1% (8/61) in the open group ( χ2=4.16, P=0.041). The cumulative survival rate after radical surgery for incidental gallbladder cancer was better in the laparoscopic group ( χ2=4.58, P=0.032). Conclusion:Compared to open surgery, laparoscopic radical surgery for incidental gallbladder cancer showed benefits in intraoperative blood loss, postoperative hospital stay, complication rates, and cumulative survival.

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.
Humans ; Aged ; Middle Aged ; COVID-19/prevention & control* ; SARS-CoV-2 ; Pandemics/prevention & control* ; China/epidemiology* ; Disease Outbreaks/prevention & control* ; Vaccination

Pathogenic microbes can induce cellular dysfunction, immune response, and cause infectious disease and other diseases including cancers. However, the cellular distributions of pathogens and their impact on host cells remain rarely explored due to the limited methods. Taking advantage of single-cell RNA-sequencing (scRNA-seq) analysis, we can assess the transcriptomic features at the single-cell level. Still, the tools used to interpret pathogens (such as viruses, bacteria, and fungi) at the single-cell level remain to be explored. Here, we introduced PathogenTrack, a python-based computational pipeline that uses unmapped scRNA-seq data to identify intracellular pathogens at the single-cell level. In addition, we established an R package named Yeskit to import, integrate, analyze, and interpret pathogen abundance and transcriptomic features in host cells. Robustness of these tools has been tested on various real and simulated scRNA-seq datasets. PathogenTrack is competitive to the state-of-the-art tools such as Viral-Track, and the first tools for identifying bacteria at the single-cell level. Using the raw data of bronchoalveolar lavage fluid samples (BALF) from COVID-19 patients in the SRA database, we found the SARS-CoV-2 virus exists in multiple cell types including epithelial cells and macrophages. SARS-CoV-2-positive neutrophils showed increased expression of genes related to type I interferon pathway and antigen presenting module. Additionally, we observed the Haemophilus parahaemolyticus in some macrophage and epithelial cells, indicating a co-infection of the bacterium in some severe cases of COVID-19. The PathogenTrack pipeline and the Yeskit package are publicly available at GitHub.
COVID-19 ; Humans ; RNA ; SARS-CoV-2/genetics* ; Single-Cell Analysis/methods* ; Transcriptome

Emerging evidence indicates that the gut microbiome contributes to the host immune response to infectious diseases. Here, to explore the role of the gut microbiome in the host immune responses in COVID-19, we conducted shotgun metagenomic sequencing and immune profiling of 14 severe/critical and 24 mild/moderate COVID-19 cases as well as 31 healthy control samples. We found that the diversity of the gut microbiome was reduced in severe/critical COVID-19 cases compared to mild/moderate ones. We identified the abundance of some gut microbes altered post-SARS-CoV-2 infection and related to disease severity, such as Enterococcus faecium, Coprococcus comes, Roseburia intestinalis, Akkermansia muciniphila, Bacteroides cellulosilyticus and Blautia obeum. We further analyzed the correlation between the abundance of gut microbes and host responses, and obtained a correlation map between clinical features of COVID-19 and 16 severity-related gut microbe, including Coprococcus comes that was positively correlated with CD3⁺/CD4⁺/CD8⁺ lymphocyte counts. In addition, an integrative analysis of gut microbiome and the transcriptome of peripheral blood mononuclear cells (PBMCs) showed that genes related to viral transcription and apoptosis were up-regulated in Coprococcus comes low samples. Moreover, a number of metabolic pathways in gut microbes were also found to be differentially enriched in severe/critical or mild/moderate COVID-19 cases, including the superpathways of polyamine biosynthesis II and sulfur oxidation that were suppressed in severe/critical COVID-19. Together, our study highlighted a potential regulatory role of severity related gut microbes in the immune response of host.
COVID-19 ; Clostridiales ; Gastrointestinal Microbiome ; Humans ; Immunity ; Leukocytes, Mononuclear ; SARS-CoV-2

Objective:To explore the postprandial plasma low-density lipoprotein cholesterol (LDL-C) changes by various detection methods.Methods:A total of 85 subjects admitted to the Second Xiangya Hospital of Central South University from November 2017 to May 2019 were included. Serum samples were collected from fasting and the 2 nd hour and the 4 th hour after breakfast. Serum lipid levels were measured with enzymatic assays and nuclear magnetic resonance spectroscopy (NMRS), and proprotein invertase subtilisin/kexin type 9 (PCSK9) levels were measured with enzyme-linked immunosorbent assays. The differences of blood lipid components at different time points were compared by Friedman two-way rank analysis of variance and Wilcoxon signed rank test, and the correlation between PCSK9 level and lipoprotein particles was analyzed by Spearman correlation. Results:Measured by enzymatic assays, compared with the fasting state, LDL-C decreased at the 2 nd hour and the 4 th hour after the meal (2.58[2.09, 3.12], 2.47[1.92, 3.02], 2.37[1.82, 2.80] mmol/L, P<0.001). Measured by NMRS, the concentration of LDL particles (1 086[830, 1 239], 1 083[848, 1 213], 1 061[814, 1 213] nmol/L, P=0.417) did not change significantly, and cholesterol in LDL particles were 2.13 (1.56, 2.54), 2.16 (1.68, 2.50), 2.06 (1.58, 2.50) mmol/L, respectively ( P=0.047)，and postprandial cholesterol in LDL particles in the 2 nd hour and in the 4 th hour did not change significantly compared with fasting ( P>0.05). while the concentration of large LDL particles (185.2[150.6,221.6], 173.0[144.8,220.3], 178.1[144.0,233.6] nmol/L, P=0.001), and the cholesterol level in large LDL particles (0.49[0.39, 0.57], 0.47[0.38, 0.57], 0.46[0.37, 0.58]mmol/L, P<0.001) decreased after the meal. The PCSK9 level also decreased significantly after the meal (299[233, 397], 257[208, 342], 251[215, 340] ng/ml, P<0.001). There was an independent positive correlation between the decrease of PCSK9 levels and the increase of remnant cholesterol detected by MNRS after the meal ( r=0.232, P=0.035). Conclusions:The postprandial LDL-C level measured by NMRS and enzymatic assays is not consistent. The decrease of LDL-C measured by enzymatic assays is not caused by the clearance of LDL particles, but by the redistribution of cholesterol in each LDL subfraction.

Objective:To investigate the computed tomography (CT) features of adenocarcinoma of esophagogastric junction (AEG) after neoadjuvant chemotherapy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 59 patients with AEG who underwent neoadjuvant chemotherapy in Peking University Cancer Hospital from February 2010 to November 2014 were collected. There were 51 males and 8 females, aged from 46 to 82 years, with a median age of 63 years. All the 59 patients underwent enhanced CT examination before and after neoadjuvant chemotherapy. Observation indicators: (1) pathological examination and neoadjuvant chemotherapy of patients with AEG; (2) results of CT examination in patients with AEG, including ① qualitative indicators of CT and ② quantitative indicators of CT. Measurement data with skewed distribution were represented as M( P25, P75) or M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed by the chi-square test. Results:(1) Pathological examination and neoadjuvant chemotherapy of patients with AEG: of the 59 patients with AEG, high-differentiated adenocarcinoma was observed in 1 patient, moderate-differentiated adenocarcinoma in 40 patients, and low-differentiated adenocarcinoma in 18 patients. Effective response to neoadjuvant chemotherapy was observed in 13 patients, including 6 patients of pathological tumor regression grading (pTRG) 0 and 7 of pTRG 1; poor response was observed in 46 patients, including 12 patients of pTRG 2 and 34 patients of pTRG 3. (2) Results of CT examination in patients with AEG. ① Qualitative indicators of CT: for the 13 patients with effective response to neoadjuvant chemotherapy, 13 had the presence of ulcers, 5 had layered enhancement, 10 had infiltration of adventitia surface, and 2 had positive extramural venous invasion (EMVI) before neoadjuvant chemotherapy; after neoadjuvant chemotherapy, 13 had shallowed or disappeared ulcers, 7 patients had changed enhancement pattern, 3 had infiltration of adventitia surface, and 1 had positive EMVI. For the 46 patients with poor response to neoadjuvant chemotherapy, 28 had the presence of ulcers, 18 had layered enhancement, 37 had infiltration of adventitia surface, and 22 had positive EMVI before neoadjuvant chemotherapy; after neoadjuvant chemotherapy, 23 had shallowed or disappeared ulcers, 7 patients had changed layered enhancement pattern, 33 had infiltration of adventitia surface and 21 had positive EMVI, respectively. There was no significant difference in the layered enhancement or infiltration of adventitia surface before neoadjuvant chemotherapy between patients with different treatment response ( χ2=0.002, 0.000, P>0.05). There were significant differences in the presence of ulcers and positive EMVI before neoadjuvant chemotherapy between patients with different treatment response ( χ2=5.591, 4.421, P<0.05). After neoadjuvant chemotherapy, there were significant differences in the changes of layered enhancement pattern, infiltration of adventitia surface and positive EMVI between patients with different treatment response ( χ2=6.359, 10.090, 4.728, P<0.05); while there was no significant difference in the shallowed or disappeared ulcers between patients with different treatment response ( χ2=1.239, P>0.05). ② Quantitative indicators of CT: for the 13 patients with good response to neoadjuvant chemotherapy, the maximum tumor height, the maximum tumor area, enhanced CT value of the lesion before neoadjuvant chemotherapy were 1.37 cm(0.94 cm, 1.88 cm), 8.9 cm 2 (4.7 cm 2, 9.9 cm 2), 53 HU(47 HU, 63 HU), respectively. After neoadjuvant chemotherapy, the above indicators were 1.17 cm(0.79 cm, 1.29 cm), 4.4 cm 2(2.5 cm 2, 6.1 cm 2), 30 HU(25 HU, 53 HU), respectively. The change rates of the maximum tumor height, the maximum tumor area, and enhanced CT value of the lesion were -23%(-42%, 9%), -51%(-60 %, -21%), -44%(-51%, 19%), respectively. For the 46 patients with poor response to neoadjuvant chemotherapy, the maximum tumor height, the maximum tumor area, enhanced CT value of the lesion were 1.57 cm(1.21 cm, 1.96 cm), 9.4 cm 2(6.6 cm 2, 13.1 cm 2), 60 HU(53 HU, 66 HU) before neoadjuvant chemotherapy, respectively. After neoadjuvant chemotherapy, the above indicators were 1.16 cm(0.94 cm, 1.37 cm), 6.2 cm 2(4.8 cm 2, 8.1 cm 2), 55 HU(47 HU, 65 HU), respectively. The change rates of the maximum tumor height, the maximum tumor area, and enhanced CT value of the lesion were -27%(-38%, -9%), -33%(-47%, -12%), -9%(-22%, 9%), respectively. There was no significant difference in the maximum tumor height, the maximum tumor area, enhanced CT value of the lesion before neoadjuvant chemotherapy between patients with different treatment response ( Z=-1.372, -1.372, -1.331, P>0.05). There was no significant difference in the maximum tumor height after neoadjuvant chemotherapy between patients with different treatment response ( Z=-0.503, P>0.05), while there were significant differences in the maximum tumor area and CT value of the lesion ( Z=-2.743, -3.049, P<0.05). There was no significant difference in the change rate of the maximum tumor height or the maximum tumor area between patients with different treatment response ( Z=0.000, -1.481, P>0.05), while there was a significant difference in the change rate of CT value of the lesion ( Z=-3.231, P<0.05). Conclusion:Effective response of AEG to neoadjuvant chemotherapy was characterized by the changes in tumor layered enhancement pattern, reduction in the maximum tumor area, reduced CT value of the lesion, negative infiltration of adventitia surface, and negative EMVI.

The ongoing pandemic of Coronavirus disease 19 (COVID-19) is caused by a newly discovered β Coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). How long the adaptive immunity triggered by SARS-CoV-2 can last is of critical clinical relevance in assessing the probability of second infection and efficacy of vaccination. Here we examined, using ELISA, the IgG antibodies in serum specimens collected from 17 COVID-19 patients at 6-7 months after diagnosis and the results were compared to those from cases investigated 2 weeks to 2 months post-infection. All samples were positive for IgGs against the S- and N-proteins of SARS-CoV-2. Notably, 14 samples available at 6-7 months post-infection all showed significant neutralizing activities in a pseudovirus assay, with no difference in blocking the cell-entry of the 614D and 614G variants of SARS-CoV-2. Furthermore, in 10 blood samples from cases at 6-7 months post-infection used for memory T-cell tests, we found that interferon γ-producing CD4
Adaptive Immunity/physiology* ; Adult ; Aged ; Antibodies, Neutralizing/blood* ; COVID-19/immunology* ; Cohort Studies ; Female ; Humans ; Immunoglobulin G/blood* ; Male ; Middle Aged ; SARS-CoV-2/immunology* ; T-Lymphocytes/physiology* ; Time Factors ; Viral Proteins/immunology*

Objective To evaluate the value of multi?slice CT?based tumor predominant feeding artery sign in the localization diagnosis of exophytic tumors in the pancreaticogastric space. Methods CT images of 34 patients with pathologically proven exophytic tumors located in the pancreaticogastric space including 20 gastric gastrointestinal stromal tumors (GIST) and 14 pancreatic tumors, 7 patients of neuroendocrine neoplasms (NEN) and 7 patients of solid pseudopapillary neoplasms (SPN) were retrospectively analyzed. Two radiologists identified the tumor feeding arteries of the tumors and made the localization diagnoses. The inter?observer agreement was evaluated by Kappa coefficient. Chi?square test or Fisher exact test was used to compare the visualization of tumor predominant feeding artery sign in the two groups. Results The tumor feeding arteries were identified in 19 of 20 gastric GISTs and 13 of 14 pancreatic tumors. The two observers had a good agreement on the origins of the tumor feeding arteries (Kappa coefficient: 0.681). There was statistically significant difference in the origins of the tumor feeding arteries between the two groups (χ2=23.86,P<0.01). The blood supplies of most GISTs originated from gastric arteries, while those of most pancreatic tumors originated from the pancreatic branch of splenic artery. The tumor predominant feeding artery sign was identified in 17 gastric GISTs (17/20, 85.0%) and 11 pancreatic tumors (11/14, 78.6%). There was no statistically significant difference in the positive rate of the sign between the two groups (P=1.000). For all tumors enrolled, the sensitivities, specificities, accuracies, positive predictive values, and negative predictive values of the sign for the localization diagnosis of gastric GISTs and pancreatic tumors were 85.0% (17/20), 92.9% (13/14), 88.2% (30/34), 94.4% (17/18), 81.3% (13/16) and 71.4% (10/14), 100.0% (20/20), 88.2% (30/34), 100.0% (10/10), 83.3% (20/24), respectively. Conclusion The tumor predominant feeding artery sign on multi?slice CT can assist in the localization diagnosis of gastric and pancreatic exophytic tumors in the pancreaticogastric space.

Objective To investigate the effects of alveolar macrophage phagocytosis on prognosis in patients with acute respiratory distress syndrome (ARDS) caused by abdominal infection. Methods ARDS patients caused by severe intra-abdominal infection admitted to intensive care unit (ICU) of Tianjin Fourth Central Hospital, Tianjin Nankai Hospital, Tianjin First Central Hospital and Tianjin Fifth Central Hospital from June 2016 to March 2018 were enrolled. The gender, age, acute physiology and chronic health evaluationⅡ(APACHEⅡ) within 24 hours of admission, neutral red phagocytosis and alkaline phosphatase activity of macrophages in bronchoalveolar lavage fluid, the length of ICU stay, total hospitalization time, hospitalization expenses, and prognosis were recorded. According to the prognosis, the patients were divided into death group and survival group, and the parameters were compared between the two groups. Pearson test was used to analyze the correlation between neutral red phagocytosis function of macrophages and alkaline phosphatase activity and other indicators. The prognosis was analyzed by binary Logistic regression combined with neutral red phagocytosis and alkaline phosphatase activity in patients, and the predictive value of both subjects on prognosis was analyzed by the receiver operating characteristic (ROC) curve. Results Twenty patients were enrolled in the study, with 8 in the death group and 12 in the survival group. Compared with the survival group, the death group was older (years old: 58.50±14.86 vs. 46.67±13.40), APACHEⅡ score was higher (21.50±3.93 vs. 13.58±4.12), neutral red phagocytosis ability and alkaline phosphatase activity of alveolar macrophages were significantly decreased (A value:0.265±0.050 vs. 0.338±0.016; μmol/L: 12.06±1.24 vs. 17.96±3.90), and the length of ICU stay was significantly longer (days: 22.00±14.59 vs. 11.50±3.17), hospitalization cost was significantly increased (10 thousand Yuan:24.17±11.02 vs. 13.44±3.53), the total hospitalization time was shorter (days: 25.25±15.01 vs. 35.67±8.58), and the difference was statistically significant (all P < 0.05). There was no significant difference in gender between the survival group and the death group [male (case): 8 vs. 6, P > 0.05]. The neutral red phagocytosis ability of alveolar macrophages in ARDS patients caused by abdominal infection was negatively correlated with age, APACHEⅡ score and the length of ICU stay (r value was -0.328, -0.572, -0.809, respectively, all P < 0.05); alkaline phosphatase activity was negatively correlated with age, APACHEⅡ score, the length of ICU stay and hospitalization expenses (r value was -0.334, -0.583,-0.470, -0.517, respectively, all P < 0.05). Binary Logistic regression analysis showed that neutral red phagocytosis [odds ratio (OR) = 0.596, 95% confidence interval (95%CI) = 0.212-0.997] and alkaline phosphatase activity (OR = 0.573, 95%CI = 0.339-0.968) were the influencing factors of prognosis (both P < 0.05). ROC curve analysis showed that the AUC of neutral red phagocytosis ability for prognosis of ARDS patients caused by abdominal infection was 0.948, and the sensitivity and specificity were 91.7% and 87.5% when the off-cut value was 0.317. The AUC of alkaline phosphatase for the prognosis of ARDS patients caused by abdominal infection was 0.813; when the cut-off value was 19.72 μmol/L, the sensitivity was 75.0%, and the specificity was 87.5%. Conclusion The alveolar macrophage phagocytosis dysfunction in ARDS patients caused by severe abdominal infection was not only related to the severity of the disease, but also increased the medical burden of patients, and significantly affected the mortality of such patients.

OBJECTIVETo investigate the accuracy of CT in preoperative discrimination of cT3 from cT4 in patients with Siewert II esophagogastric junction (EGJ) adenocarcinoma according to UICC/AJCC 8th edition and IGCA 4th edition.

METHODSCT imaging data of 43 consecutive patients with Siewert II EGJ adenocarcinoma who underwent preoperative CT and were diagnosed as pT3 or pT4 by postoperative pathology were retrospectively analyzed. Inclusion criteria were as follows:(1)no previous history of gastric operation, radiochemotherapy, targeted treatment; no contraindications of CT enhanced scanning; (2) good filling of gastric cavity by CT, clear image without artifacts, all axial-coronal-sagittal 3-plane reconstruction images obtained by abdominal stage 3 enhanced scan; (3) operation within 1 week after CT examination; (4) Siewert II EGJ adenocarcinoma confirmed by operation, pT3 and pT4 by postoperative pathology. Transverse and multiplanar reconstruction images were reviewed by two radiologists in double-blind method. Distance between cancer epicenter and esophagogastric junction line, and the contour of the serosa were retrospectively measured on CT scans. The cT staging judgment was performed according to the UICC/AJCC 8th edition (Siewert II EGJ adenocarcinoma should be staged as esophageal cancer) and IGCA 4th edition (Siewert II EGJ adenocarcinoma should be staged as gastric cancer) respectively. Consistency of cT staging and pathological pT staging was compared between UICC/AJCC and IGCA.

RESULTSPreoperative CT revealed that the mean length between tumor epicenter and esophagogastric junction line was(1.5±0.4) cm (0.7-2.5 cm), and such length was ≤2 cm in 41 cases, whose concordance with surgical judgment was 95.3%(41/43). IGCA staging: 18 cases were preoperatively assessed as cT3 and 25 cases as cT4a. UICC/AJCC staging: 41 cases with cancer epicenter locating within 2 cm below esophagogastric junction line were staged as cT3 according to esophageal cancer staging; 2 cases with cancer epicenter locating > 2 cm below esophagogastric junction line were staged according to gastric cancer staging, of whom one was staged as cT3 due to regular serosa and the other was staged as cT4a due to irregular serosa. Postoperative pathology: 33 cases were pT3 and 10 cases were pT4a. The accuracy of preoperative CT in discrimination of T3 from T4a was 74.4%(32/43) with UICC/AJCC criteria and 65.1%(28/43) with IGCA criteria, whose difference was significant(P<0.01).

CONCLUSIONSPreoperative CT can accurately localize the 2 cm threshold line of Siewert II esophagogastric junction adenocarcinoma, which is beneficial to the discrimination of cT3 from cT4a EGJ adenocarcinoma. Application of the UICC/AJCC 8th edition criteria to above discrimination has higher accuracy as compared to IGCA 4th edition in cT-staging by CT.

Adenocarcinoma ; Double-Blind Method ; Esophageal Neoplasms ; diagnostic imaging ; Esophagogastric Junction ; Humans ; Neoplasm Staging ; Retrospective Studies ; Stomach Neoplasms ; diagnostic imaging ; Tomography, X-Ray Computed