Histopathological Diagnosis System for Gastritis Using Deep Learning Algorithm / 中国医学科学杂志(英文版)

Objective To develope a deep learning algorithm for pathological classification of chronic gastritis and assess its performance using whole-slide images (WSIs). Methods We retrospectively collected 1,250 gastric biopsy specimens (1,128 gastritis, 122 normal mucosa) from PLA General Hospital. The deep learning algorithm based on DeepLab v3 (ResNet-50) architecture was trained and validated using 1,008 WSIs and 100 WSIs, respectively. The diagnostic performance of the algorithm was tested on an independent test set of 142 WSIs, with the pathologists' consensus diagnosis as the gold standard. Results The receiver operating characteristic (ROC) curves were generated for chronic superficial gastritis (CSuG), chronic active gastritis (CAcG), and chronic atrophic gastritis (CAtG) in the test set, respectively.The areas under the ROC curves (AUCs) of the algorithm for CSuG, CAcG, and CAtG were 0.882, 0.905 and 0.910, respectively. The sensitivity and specificity of the deep learning algorithm for the classification of CSuG, CAcG, and CAtG were 0.790 and 1.000 (accuracy 0.880), 0.985 and 0.829 (accuracy 0.901), 0.952 and 0.992 (accuracy 0.986), respectively. The overall predicted accuracy for three different types of gastritis was 0.867. By flagging the suspicious regions identified by the algorithm in WSI, a more transparent and interpretable diagnosis can be generated. Conclusion The deep learning algorithm achieved high accuracy for chronic gastritis classification using WSIs. By pre-highlighting the different gastritis regions, it might be used as an auxiliary diagnostic tool to improve the work efficiency of pathologists.

Safety and efficacy of transcatheter tricuspid valve replacement with LuX-Valve in patients with severe tricuspid regurgitation / 中华心血管病杂志

Objectives: To evaluate the safety and efficacy of LuX-Valve on the treatment of severe tricuspid regurgitation (TR). Methods: This is a prospective observational study. From September 2018 to March 2019, 12 patients with severe TR, who were not suitable for surgery, received LuX-Valve implantation in Changhai Hospital. LuX-Valve was implanted under general anesthesia and the guidance of transesophageal echocardiography and X-ray fluoroscopy. Access to the tricuspid valve was achieved via a minimally invasive thoracotomy and transatrial approach. Main endpoints were surgery success and device success. Surgery success was defined as successful implanting the device and withdrawing the delivery system, positioning the valve correctly and stably without severe or life-threatening adverse events. Device success was defined as satisfied valve function (TR severity reduction ≥ 2 grades, tricuspid gradient ≤ 6 mmHg (1 mmHg=0.133 kPa)), absence of malposition, valve failure and reintervention, major adverse events including device related mortality, embolization, conduction system disturbances and new onset shunt across ventricular septum at day 30 post implantation. Results: A total of 12 patients with severe to torrential TR were included in this study. The age was (68.5±6.9) years and 7 were female. All patients had typical right heart failure symptoms. Procedural success was achieved in all cases, there was no intraprocedural mortality or transfer to open surgery. TR significantly improved after LuX-Valve implantation (none/trivial in 8 patients, mild in 3 patients and moderate in 1 patient). The average device time was (9.2±4.2) minutes. Intensive care unit duration was 3.0 (2.0, 4.8) days. One patient died at postoperative day 18 due to non-surgery and device reasons. Transthoracic echocardiography at 30 days after operation showed that TR was significantly reduced (none/trivial in 8 patients, mild in 2 patients and moderate in 1 patient) and device success was achieved in 11 cases. All survived patients experienced a significant improvement in life quality with significantly improvement in New York Heart Association (NYHA) classification (Ⅰ and Ⅱ: 6/11 post operation vs. 0/11 before operation, P=0.012) and there were no device related complications in this patient cohort. Conclusions: LuX-Valve implantation is feasible, safe and effective for the treatment of patients with severe TR.

Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients / 中华医学杂志(英文版)

Background@#A patient’s infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence.@*Methods@#The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients’ oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed.@*Results@#In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0–62.0) years were analyzed. After in-hospital treatment, patients’ inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0–11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients’ stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0–16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0–4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients’ urine specimens after throat swabs were negative. Using a multiple linear regression model (F=2.669, P=0.044, and adjusted R2=0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients’ stools (t=-2.699, P=0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs 8.0 days, respectively; t=2.550, P=0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs 11 days, respectively; t=4.631, P <0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P >0.05).@*Conclusions@#In brief, as the clearance of viral RNA in patients’ stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.

Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients / 中华医学杂志(英文版)

BACKGROUND@#A patient's infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence.@*METHODS@#The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients' oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed.@*RESULTS@#In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0-62.0) years were analyzed. After in-hospital treatment, patients' inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0-11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients' stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0-16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0-4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients' urine specimens after throat swabs were negative. Using a multiple linear regression model (F = 2.669, P = 0.044, and adjusted R = 0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients' stools (t = -2.699, P = 0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t = 2.550, P = 0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t = 4.631, P  0.05).@*CONCLUSIONS@#In brief, as the clearance of viral RNA in patients' stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.

Endolymphatic sac tumor with von Hippel-Lindau disease: report of two cases with testing of von Hippel-Lindau gene / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>Endolymphatic sac tumors (ELSTs) are rare in the general population with much higher prevalence in von Hippel-Lindau(VHL) disease. The purpose of this study is to present two cases of endolymphatic sac tumor with VHL disease with analysis of VHL gene and to explore their association with VHL disease using molecular analysis.</p><p><b>METHODS</b>Clinical data of these two patients from different VHL families were studied. DNAs extracted from peripheral bloods were amplified by the polymerase chain reaction using oligonucleotide primers corresponding to the VHL gene, then compared the mutations with the Human Gene Mutation Database.</p><p><b>RESULTS</b>In case 1, 6 family members were enrolled in the study. Among them, three had been identified to have a germline missense point mutation at codon 194 of the VHL gene exon 1 (p.S65W). The little sister of the patient (case 1) underwent vitrectomy for retinal hemangioblastoma 5 years ago in another hospital. The mother of the patient (case 1) was further diagnosed to have a cerebellar hemangioblastoma and renal carcinoma in the following physical examination. Case 2 with her parents were also tested. Codon 499 of the VHL gene exon 3 (p.R167W) were detected in case 2 and her mother, but the mother refused further examination.</p><p><b>CONCLUSIONS</b>The genetic diagnosis plays an important role in early detection of symptomatic patients and suspected patients. Clinical screening for members of the VHL families, and close follow-up of carriers allow an early detection of tumors and the metastasis, which is the most common cause of death of these patients.</p>

Clinical and pathologic features of renal mucinous tubular and spindle cell carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinical and pathological features of the mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney.</p><p><b>METHODS</b>Seven cases of MTSCC were analyzed by gross examination and light microscopy. Immunostaining was performed to detect the expression of CD10, CK7, CK18, CK19, Villin, EMA, P504S and vimentin. The literature on this tumor was reviewed to discuss the histological features of MTSCC and its clinical behavior.</p><p><b>RESULTS</b>Three of 7 cases were male and the other 4 were female. The mean age of the patients was 48.2 years old, with a range from 39 to 61 years. All the patients presented no symptom and their tumors were found by health examination. Tumors averaged 5.5 cm in greatest dimension (range from 4.0 cm to 9.0 cm). The tumors were well-circumscribed without capsules, and the cut surfaces were solid and soft with white-tan color. By light microscopy, tumors were composed of tightly packed, small, elongated tubules with transitions to spindle cell components. Five cases had mucinous stroma. Clear cell clusters, focal sarcomatoid differentiation, papillations and foamy macrophages were seen in several cases. Immunohistochemically, all 7 cases showed positive for CK7, five of 5 cases positive for EMA, CK18 and P504S, four of 5 cases positive for CK19, but heterogeneous for CD10, villin and vimentin expression. No evidence of local recurrence or distant metastases was identified in the 5 patients with follow-up information.</p><p><b>CONCLUSIONS</b>The mucinous tubular and spindle cell carcinoma is a low-grade and polymorphic neoplasm. The morphology of these tumors may not be uniform with a wide histological spectrum. The tumors can be tubular predominant or spindle cells predominant with scant to abundant mucinous stroma, which coupled with the presence of other unusual features such as clear cells, papillations, foamy macrophages, necrosis and sarcomatoid differentiation. Immunohistochemically, MTSCC can express the markers from the proximal convoluted tubules to collecting tubules.</p>

Strategy of dealing with left subclavian artery in total arch replacement combined with stented elephant trunk implantation for Stanford type A aortic dissection / 中华外科杂志

<p><b>OBJECTIVE</b>To summarize the experiences of ligating left subclavian artery (LSA) in total arch replacement and stented elephant trunk implantation for Stanford type A aortic dissection patients with difficulty in exposing the LSA.</p><p><b>METHODS</b>Total arch replacement and stented elephant trunk implantation were performed on 79 consecutive patients from January 2008 to June 2010. Twenty-nine cases of the cohort undertook LSA ligation due to bad exposure. There were 21 males and 8 females patients, aged from 19 to 55 years with a mean of (44 ± 12) years. There were 12 acute dissections, 4 sub-acute dissections and 13 chronic dissections. Based on thoroughly evaluation of the Willis' circle and bilateral vertebral arteries through pre-operative imaging and intra-operative circulative parameters, if the collateral circulation was considered sufficient, LSA was ligated directly and only the innominate artery and carotid artery were reconstructed; if considered insufficient, an additional bypass from ascending aorta to left axillary artery was performed.</p><p><b>RESULTS</b>All the 29 operations were completed successfully. There was one patient died from pulmonary infection and the others recovered well.Blood pressure of left arms were lower than right postoperatively [(78 ± 17) mmHg vs. (126 ± 24) mmHg, 1 mmHg = 0.133 kPa, P < 0.01], but oxygen saturation, skin temperature and strength of the left hand were normal compared to the right. All the survived patients have been followed 1 - 27 months and none of them presented with any symptoms of left subclavian artery steal syndrome and ischemia of left arms.</p><p><b>CONCLUSIONS</b>Ligation of LSA under strict evaluation of collateral circulation could be safe in Type A dissection patients with bad exposure due to big ascending aortic aneurysm and will simplify the procedure significantly.</p>

Congenital quadricuspid aortic valve: analysis of 11 surgical cases / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Congenital quadricuspid aortic valve is rarely seen during aortic valve replacement (AVR). The diagnosis and treatment of the disease were reported in 11 cases.</p><p><b>METHODS</b>Eleven patients (nine men and two women, mean age 33.4 years) with quadricuspid aortic valve were retrospectively evaluated. Medical records, echocardiograms and surgical treatment were reviewed.</p><p><b>RESULTS</b>In accordance with the Hurwitz and Roberts classification, the patients were classified as type A (n = 2), type B (n = 7), type F (n = 1) and type G (n = 1). Three patients were associated with other heart diseases, including infective endocarditis and mitral prolaps, left superior vena cava, aortic aneurysm. All had aortic regurgitation (AR) except two with aortic stenosis (AS), detected by color-flow Doppler echocardiography. The congenital quadricuspid aortic valve deformity in seven patients was diagnosed by echocardiography. All patients underwent successful aortic valve replacement.</p><p><b>CONCLUSION</b>Quadricuspid aortic valve is a rare cause of aortic insufficiency, while echocardiography plays an important role in diagnosing the disease. Aortic valve replacement is the major therapy for the disease.</p>

Three cases of primary renal lymphoma / 中国实验血液学杂志

Primary renal lymphoma (PRL) is very rare. In order to investigate the clinical features, diagnosis, therapy and prognosis of PRL, three cases of primary renal lymphoma diagnosed definitely and treated in our hospital in the recent ten years were reported, and their clinical features, laboratory examination, pathological observation and their therapeutics were analyzed. The results indicated that the three cases of primary renal lymphoma were all male elders. Their most common symptoms were flank pain along with abdominal mass and hematuria, etc. Because of suspicion of cancer with renal involvement, the three patients all underwent laparotomy. Histological examination showed diffuse B-cell lymphoma in the three cases, and the immunophenotype was CD20 positive in all three cases. These cases were treated with combined therapeutics, including rituximab, intermittent interferon and local radiotherapy. The 2 out of 3 cases lived for more than 5 years after therapy. In conclusion, as PRL is especially rare, and often diagnosed mistakenly, it is suggested that early and definite diagnosis and individualization of treatment for PRL patients may be possible to achieve a better therapeutic result.

Evaluation of surgical technique and indication on descending aortic aneurysms / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the surgical technique and indication on descending aortic aneurysms.</p><p><b>METHODS</b>From January 1996 to June 2006, 41 patients with descending aortic aneurysm underwent operation, including DeBakey type III dissection in 26, false aneurysm in 6, true aneurysm in 4, and residual or newly complicated type III dissection after the surgery of Marfan syndrome in 5. Operations were performed by left heart bypass in 9, femoral-femoral bypass in 7, pulmonary-femoral bypass in 2, and deep hypothermic circulatory arrest in 23. The whole thoracic descending aorta was replaced in 15, and intercostal arteries were reimplanted in 12.</p><p><b>RESULTS</b>One patient died of acute renal failure with the hospital mortality 2.4%. Main complications: respiratory dysfunction in 6, renal dysfunction in 6, recurrent nerve injuries in 4, chylothorax in 2, and no paraplegia.</p><p><b>CONCLUSIONS</b>Surgical intervention of descending aortic aneurysm still has its unique advantages and indications; surgical safety is markedly improved by the use of deep hypothermic circulatory arrest.</p>

The surgical procedure and clinical results of Stanford A aortic dissection / 中华胸心血管外科杂志

Objective To evaluate the methods and consequences of surgical technique in the treatment of Stanford A aortic dissection.Methods 108 patients with type Standford A aortic dissection underwent surgery in our study,including urgent surgery in 53 and selective surgery in 55.The operation was performed under deep hypothennic circulatory arrest (DHCA) in 85 cases.Surgical procedures included ascending and semi arch replacement or total arch replacement (some cases combined with stented graft implanted into the descending aorta),"elephant trunk" procedure.Concomitant procedures included repair of intimal tear in arch or descending aorta,Bentall procedure,aortic valve replacement,Cabrol or modified Cabrol procedure,aortic valvuloplasty,mitral valvuloplasty or mitral valve replacement,tricuspid valvuloplasty and CABG.Results In-hospital mortality was 6.5% (7 of 108 patients).The mor- tality was 7.5% (4 of 53 patients) in urgent surgery group and in elective surgery group was 5.4% (3 of 55 patients).Ninety six percent survived patients were followed up for 1 month to 13.3 years [mean (3.2?1.3) years] and 2 deaths occurred during the fel- low-up period.3 patients underwent re-operatian.Conclusion The choice of surgical procedures depend on the location of intimal tear for Stanford A aortic dissection.The better operative effects can be expected with proper surgical indication,perfecting surgical technique,and enhancing postoperative treatment.

COVID-19 severity is associated with immunopathology and multi-organ damage

COVID-19 is characterised by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand how host responses contribute to COVID-19 pathophysiology, we used a multi-omics approach to identify molecular markers in peripheral blood and plasma samples that distinguish COVID-19 patients experiencing a range of disease severities. A large number of expressed genes, proteins, metabolites and extracellular RNAs (exRNAs) were identified that exhibited strong associations with various clinical parameters. Multiple sets of tissue-specific proteins and exRNAs varied significantly in both mild and severe patients, indicative of multi-organ damage. The continuous activation of IFN-I signalling and neutrophils, as well as a high level of inflammatory cytokines, were observed in severe disease patients. In contrast, COVID-19 in mild patients was characterised by robust T cell responses. Finally, we show that some of expressed genes, proteins and exRNAs can be used as biomarkers to predict the clinical outcomes of SARS-CoV-2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID-19 and will help guide future studies in this area.

Total Infectomes Characterization of Respiratory Infections in pre-COVID-19 Wuhan, China

At the end of 2019 Wuhan witnessed an outbreak of "atypical pneumonia" that later developed into a global pandemic. Metagenomic sequencing rapidly revealed the causative agent of this outbreak to be a novel coronavirus - SARS-CoV-2. Herein, to provide a snapshot of the pathogens in pneumonia-associated respiratory samples from Wuhan prior to the emergence of SARS-CoV-2, we collected bronchoalveolar lavage fluid samples from 408 patients presenting with pneumonia and acute respiratory infections at the Central Hospital of Wuhan between 2016 and 2017. Unbiased total RNA sequencing was performed to reveal their "total infectome", including viruses, bacteria and fungi. Consequently, we identified 37 pathogen species, comprising 15 RNA viruses, 3 DNA viruses, 16 bacteria and 3 fungi, often at high abundance and including multiple co-infections (12.8%). However, SARS-CoV-2 was not present. These data depict a stable core infectome comprising common respiratory pathogens such as rhinoviruses and influenza viruses, an atypical respiratory virus (EV-D68), and a single case of a sporadic zoonotic pathogen - Chlamydia psittaci. Samples from patients experiencing respiratory disease on average had higher pathogen abundance than healthy controls. Phylogenetic analyses of individual pathogens revealed multiple origins and global transmission histories, highlighting the connectedness of the Wuhan population. This study provides a comprehensive overview of the pathogens associated with acute respiratory infections and pneumonia, which were more diverse and complex than obtained using targeted PCR or qPCR approaches. These data also suggest that SARS-CoV-2 or closely related viruses were absent from Wuhan in 2016-2017.

Complete genome characterisation of a novel coronavirus associated with severe human respiratory disease in Wuhan, China

Emerging and re-emerging infectious diseases, such as SARS, MERS, Zika and highly pathogenic influenza present a major threat to public health1-3. Despite intense research effort, how, when and where novel diseases appear are still the source of considerable uncertainly. A severe respiratory disease was recently reported in the city of Wuhan, Hubei province, China. At the time of writing, at least 62 suspected cases have been reported since the first patient was hospitalized on December 12nd 2019. Epidemiological investigation by the local Center for Disease Control and Prevention (CDC) suggested that the outbreak was associated with a sea food market in Wuhan. We studied seven patients who were workers at the market, and collected bronchoalveolar lavage fluid (BALF) from one patient who exhibited a severe respiratory syndrome including fever, dizziness and cough, and who was admitted to Wuhan Central Hospital on December 26th 2019. Next generation metagenomic RNA sequencing4 identified a novel RNA virus from the family Coronaviridae designed WH-Human-1 coronavirus (WHCV). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that WHCV was most closely related (89.1% nucleotide similarity similarity) to a group of Severe Acute Respiratory Syndrome (SARS)-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) previously sampled from bats in China and that have a history of genomic recombination. This outbreak highlights the ongoing capacity of viral spill-over from animals to cause severe disease in humans.