Degradation of SARS-CoV-2 receptor ACE2 by the E3 ubiquitin ligase Skp2 in lung epithelial cells / 医学前沿

An unexpected observation among the COVID-19 pandemic is that smokers constituted only 1.4%-18.5% of hospitalized adults, calling for an urgent investigation to determine the role of smoking in SARS-CoV-2 infection. Here, we show that cigarette smoke extract (CSE) and carcinogen benzo(a)pyrene (BaP) increase ACE2 mRNA but trigger ACE2 protein catabolism. BaP induces an aryl hydrocarbon receptor (AhR)-dependent upregulation of the ubiquitin E3 ligase Skp2 for ACE2 ubiquitination. ACE2 in lung tissues of non-smokers is higher than in smokers, consistent with the findings that tobacco carcinogens downregulate ACE2 in mice. Tobacco carcinogens inhibit SARS-CoV-2 spike protein pseudovirions infection of the cells. Given that tobacco smoke accounts for 8 million deaths including 2.1 million cancer deaths annually and Skp2 is an oncoprotein, tobacco use should not be recommended and cessation plan should be prepared for smokers in COVID-19 pandemic.

Clinical Features of Coccidioidomycosis:Analysis of 33 Chinese Cases / 中国医学科学院学报

Objective To summarize the characteristics of Chinese coccidioidomycosis cases, improve the diagnosis and treatment of this disease and prevent misdiagnosis as well as therapeutic error.Methods Search in databases including Medline,Wanfang,and CNKI using "Coccidioidomycosis" and "China" as index words yielded 23 articles that reported a total of 32 Chinese coccidioidomycosis cases.In addition,one patient with disseminated coccidioidomycos was treated in our center in April 2016.The demographic data,site of infection,clinical manifestations,past medical history,exposure history,imaging and laboratory findings,and pathological features of these 33 patients were analyzed.Results Among these 33 patients,7(21.2%)had visited an epidemic area and 6(18.2%)were immunocompromised.The disease involved the respiratory system,skin,bone,central nervous system,cornea,and stomach in 24,6,3,2,1,and 1 patients,respectively.Eight patients (24.2%) had multiple system involvement,and three of them died.The imaging findings included pulmonary nodules(=14),mediastinal lymphadenopathy(=5),solid shadow(=4),cavity(=4),pleural effusion(=3),multiple plaques(=2)and masses(=2).Coccidiolys cysts were detected in the affected tissues(=28)or in pus,exudate or pleural smear(=3);in addition,coccidioides mycelium and spores were found in the sputum,pus,and tissue cultures in 4 cases,among whom only 2 cases were confirmed by serological examination.The treatments included triazoles(=20),systemic or local administration of amphotericin B(=13),surgical resection of the lesion(=8),and intravenous gamma globulin(=1).Five patients died,among whom three had underlying diseases that caused immunosuppression and one was an infant.The prognoses were relatively good in the remaining patients.Conclusions Early diagnosis and proper treatment can achieve good prognosis in coccidioidomycosis patients.Multi-system involvement and immunosuppression are risk factors for poor prognosis of coccidioidomycosis.For these patients,adequate and full-course medication may prevent rapid disease progression.

Immunoglobulin G4-related diseases mimics Rosai-Dorfman diseases: a series of 6 cases in China / 中华风湿病学杂志

Objective To summarize the clinical and pathologic characteristics of patients with RosaiDorfman disease (RDD) mimicking immunoglobulin (Ig) G4-related disease (IgG4-RD).Methods Retrospectively analyze the clinical manifestations,laboratory tests,pathologic features,treatment and prognosis of RDD patients whose clinical presentations mimicked IgG4-RD in Peking Union Medical College Hospital during January 2015 to June 2017.Results Six RDD patients mimicking IgG4-RD were described,which accounted for 1.5％ of the 450 registered IgG4-RD patients.All patients were male,with the median age of 53 year and the median disease duration of 12 months.All patients had extra-nodal involvements,of which the locations included spinal cord (3/6),intracranial (2/6),skin (2/6) and liver (1/6).Increased serum IgG4 (＞1 350 mg/L) was found in 4 cases (1 360-6 410 mg/L).Seven specimens were obtained from these patients.The number of IgG4-positive plasma cells was found to be more than 50 per HPF in 3 cases,30 per HPF in 1 case.The IgG4/IgG ratio was 40％ in 2 specimens,between 10％ and 30％ in 2 specimens and 10％ in 2 specimens.All patients were treated by glucocorticoids and 4 of them were treated with combined cyclophosphamide.Five patients got partial remission by these treatments while 1 patient withdrew from further follow up.Conclusion RDD is one of the mimics of IgG4-RD.There are several differences in lab tests and pathologic features between RDD and IgG4-RD.Before the IgG4-RD is diagnosed,RDD should be excluded by specific pathologic manifestations at the first place.

The clinical characteristics of 346 patients with IgG4-related disease / 中华内科杂志

Objective To analyze the clinical characteristics of IgG4-related disease (IgG4-RD)so as to improve the understanding of IgG4-RD in China.Methods IgG4-RD patients were recruited from Peking Union Medical College Hospital between January 2011 and January 2016.All patients were followedup for more than 6 months.The demographic characteristics,symptoms,organ involvements,laboratory examinations and treatment efficacy were evaluated and analyzed.Results A total of 346 patients were finally enrolled,including 230 males (66.5％) and 116 females (33.5％).The mean age of disease onset was (53.8 ± 14.2) years old.The mostly common involved organs were lymph nodes (56.4％) and submandibular glands (52.6％).Other affected organs and manifestations included:swelling of the lacrimal glands (46.5％),autoimmune pancreatitis (38.4％),pulmonary involvement (28.0％),sclerosing cholangitis (25.4％),naso-sinusitis (23.4％),parotid gland swelling (21.7％),retroperitoneal fibrosis (19.9％),large arteries involvement (9.5％),kidney involvement (obstructive nephropathy caused by retroperitoneal fibrosis was excluded) (6.9％),skin lesions (6.4％).Rare features consisted of thyroid glands,pituitary glands,gastrointestinal tract,pachymeningitis,pericardium,sclerosing mediastinitis and orchitis.The majority of patients had multi-organ involvement,such as 74.3％ patients with 3 and more,18.2％ and 7.5％ patients with 2 and single organ involvement respectively.The average IgG4-RD responder index (IgG4-RD RI) was 13.21 ±5.70.History of allergy was found in 172 (49.7％) patients.As to the laboratory tests,elevated serum IgG4 levels were confirmed in 285 (94.1％) patients,which was positively correlated with IgG4-RD RI.There were 33.5％ patients receiving monotherapy of glucocorticoid,52.6％ treated with glucocorticoids combined with immunosuppressive agents,4.9％ patients with immunosuppressant only,and 9.0％ patients with mild disease not receiving medication.The majority (336,97.1％) patients improved the above regimens.Conclusion IgG4-RD is a systemic fibro-inflammatory disease with multiple organ involvement.The mostly common involved organs include lymph node,submandibular glands,and pancreas.Glucocorticoids and immunosuppressive agents were effective for IgG4-RD.

IgG4 immunohistochemistry in Riedle thyroiditis / 中华病理学杂志

Objective@#To observe the histopathological changes and immunohistochemical expression of IgG4 in Riedle thyroiditis (RT) and to study the relationship between RT and IgG4-related diseases (IgG4-RD).@*Methods@#A total of 5 RT patients were collected from the Department of Pathology, Peking Union Medical College Hospital during April 2012 to August 2014. The clinical and immunohistochemical features were analyzed in the 5 patients. Histopathologic analysis was performed on hematoxylin and eosin-stained sections.@*Results@#There were one male and four female patients, aged 52 to 78 years (median 59 years). Five cases were characterized by multiple nodules of thyroid, which increased year by year. All patients were found to have surrounding tissue compression symptoms and signs. Two female patients were found to have hypothyroidism. The serum concentration of IgG was elevated in 2 cases, and the serum concentration of IgG was not tested before operation in the remaining patients. By ultrasound, all presented as low echo or medium low echo. Strong echo occasionally appeared in hypoechoic nodules. Microscopically, fibrous tissue hyperplasia was infiltrated with varying numbers of lymphocytes and plasma cells. The occlusion of phlebitis was found in 4 cases and eosinophils were found in 3 cases. IgG4 counts and IgG4/IgG ratios in 5 cases were 20/HPF, 16%; 60/HPF, 82%; 22/HPF, 28%; 400/HPF, 266% and 33/HPF, 71%, respectively.@*Conclusions@#With the similar pathological manifestations between RT and IgG4-RD, immunohistochemical staining shows that the number of IgG4 positive plasma cells and IgG4/IgG ratio of RT are increased in varying degrees. Some cases meet the diagnostic criteria of IgG4-RD, and speculate that some cases of RT belong to IgG4-RD.

Expression of CD133 in rectal cancer tissues and its relationship with neoadjuvant chemoradiotherapy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the association of CD133 expression in rectal cancer tissues with neoadjuvant chemoradiotherapy (nCRT) and tumor regression grading (TRG) after nCRT.</p><p><b>METHODS</b>Radical resected rectal cancer specimens and clinicopathological data of 105 patients, including 60 men and 45 women with median age of 59 years, diagnosed as locally advanced rectal cancer in Peking Union Medical College Hospital from January 2008 to December 2014 were collected retrospectively. Thirty-nine and 66 cases were histologically classified as good-moderate and poor differentiation respectively. Sixty-eight and 37 cases were clinically graded as stage I(-II( and III(-IIII( in preoperative assessment respectively. NCRT was administered in 61 cases before surgery (nCRT group). The nCRT consisted of preoperative pelvic radiotherapy using 50 Gy (2 Gy once, for 25 sessions) with FOLFOX regimen (5-fluorouracil plus oxaliplatin) for 2-3 cycles or XELOX regimen (capecitabine plus oxaliplatin) for 2 cycles. Patients underwent surgery after 6 courses of nCRT, and then received the same previous chemotherapy regimen. In nCRT group, biopsy specimens before nCRT were obtained in 45 cases. Forty-four cases received surgery alone without nCRT (surgery alone group). CD133 expression was tested by immunohistochemical Envision two-step methods. The histological TRG evaluation was performed in the nCRT group. TRG score 0-2 was defined as insensitivity to nCRT, whereas TRG score 3-4 was defined as sensitivity. CD133 expression in rectal cancer samples before and after nCRT was compared. Association of CD133 expression with TRG after nCRT was examined.</p><p><b>RESULTS</b>No significant differences of baseline parameters were found between nCRT group and surgery alone group (all P>0.05). The positive rate of CD133 in nCRT group was 70.4%(43/61,) which was significantly higher than that in surgery alone group (47.7%, 21/44)(χ(2)=5.566, P=0.018) and that in biopsy samples before nCRT group (44.4%, 20/45)(χ(2)=7.287, P=0.007). Twenty-two cases (36.1%, 22/61) in nCRT group had TRG score of 3-4 . Among these 22 cases, 11 cases were negative CD133, and constituted 61.1% (11/18) of all CD133-low expression cases in nCRT group, whereas the other 11 cases were positive CD133, and constituted 25.6%(11/43) of all CD133-high expression cases in nCRT group (χ(2)=6.974, P=0.008).</p><p><b>CONCLUSION</b>The CD133 expression up-regulates markedly in rectal cancer after nCRT and nCRT may have potential positive modulation on CD133 expression. CD133-positive cancer reveals lower response to nCRT, suggesting CD133 may be a potential target for improving efficacy of nCRT in rectal cancer.</p>

Study on pathological characteristics of eutopic endometrium in endometriosis / 中华妇产科杂志

Objective To study the pathologic characteristics of eutopic endometrium in patients with endometriosis.Methods Pathologic characteristics of eutopic endometrium were studied in 176 patients with endometriosis in Peking Union Medical College Hospital from January 2007 to December 2008 retrospectively.Results About 72.2％(127/176)of eutopic endometrium were in proliferative phase,19.9％(35/176)of were observed as endometrial polyp,including 32 cases with simple endometrial polyp and 3 cases with abnormal hyperplasia combined with endometrial polyp.And 4.0％(7/176)showed abnormal hyperplasia.The incidence of pathologic changes in eutopic endometrium was 22.2％(39/176).Among 53 endometriosis patients combined with infertility,the incidence of pathologic changes of eutopic endometrium was 35.9％(19/53),which was significantly higher than 16.3％ in non-infertile patients (x2 =8.24,P =0.004).Among 65 cases with irregular menstruation,the incidence of endometrial polypus and endometrial hyperplasia were 20.0％(13/65)and 10.8％(7/65),which were significantly higher than 17.1％(19/111)and 0 in normal menstruation patients(x2 =13.839,P =0.003).Conclusions The eutopic endometrium of endometriosis were in proliferative phase state.The pathologic changes of eutopic endometrium were more in patients combined with infertility and irregular menstruation.

Clinical analysis of mucinous tubular and spindle cell carcinoma of the kidney / 中华泌尿外科杂志

Objective To explore the clinical features, treatment and prognosis of mucinous tubular and spindle cell carcinoma of the kidney. Methods Patient 1, a 42-year-old woman presented with space-occupying lesion of the lower pole of the left kidney with no symptoms in physical examination for 1 week. CT revealed a low-enhanced tumor located in the lower pole of the left kidney in cT1b N0M0. Radical left nephrectomy was performed. Patient 2, a 76-year-old woman presented with space-occupying lesion of the middle of the left kidney with no symptoms in physical examination for 10 d. CT revealed a low-enhanced tumor located in the middle of the left kidney in cT1b N0 M0. Laparoscopic radical left nephrectomy was performed. The patient received adjuvant treatment with IL-2 and interferon-α 3 months after nephrectomy. Patient 3, a 50-year-old woman presented with lumbago for 3 months. CT revealed a low-enhanced tumor located in the right kidney in cT2 N0 M0. Radical right nephrectomy was performed. The patient received adjuvant treatment with IL-2 and interferon-α 3months after nephrectomy. Patient 4, a 60-year-old woman presented with lumbago and hematuria for 15 d. CT revealed a low-enhanced tumor located in the lower pole of the left kidney in cT1a N0M0.Radical left nephrectomy was performed. Results Histological examination of the tumors showed that they consisted of spindle cells arranged in tubular and trabecular patterns embedded in a myxoid stroma. Pathologic diagnosis of all 4 patients were MTSCCa. There was no evidence of recurrence in all patients for 9- 46 months. Conclusions MTSCCa is a rare low-grade renal cell carcinoma.There is a female predominance. Early surgical excision is the best treatment and the prognosis is relatively good.

CT characteristics of thoracoabdominal localized Castleman disease / 中华放射学杂志

Objective To assess the CT characteristics of thoracoabdominal localized Castleman disease (LCD) in 55 cases and correlate with histopathologic features. Methods Fifty-five patients with LCD proved histopathologically in thorax ( n = 25 ) and abdomen ( n = 30 ) were collected during past 20 years. The unenhanced and contrast-enhanced CT were performed in all patients. Two radiologists reviewed CT images and the CT findings were analyzed simultaneously. Results In 54 patients with hyaline-vascular type ( n = 50 ) and mixed type ( n = 4 ) localized CD, the lesion typically presented as solitary mass (90. 7% , 49 cases), with irregular or lobular or infiltrative margin ( 83.3% , 45 cases),central calcification (38. 9%, 21 cases), marked enhancement (100% , 54 cases), focal non-necrosis low attenuation areas (72. 2%, 39 cases), lymphadenopathy (70.4%, 38 cases) and dilated feeding vessels adjacent to the mass (96.3%, 52 cases). One lesion with plasma cell type localized CD presented as a mass with irregular margin, mild enhancement and central necrosis. Four morphologic patterns wereclassified on CT, including solitary mass with well-circumscribed margin (n =4), irregular or lobular margin ( n = 30), infiltrative or halo-like margin ( n = 16 ), and multiple coalescent maasses ( n = 5 ). Conclusion CT features of thoracoabdominal localized CD are closely related to the location and pathological type. LCD with hyaline-vascular and mixed type has typical CT characteristics, while LCD with plasma cell type has no typical CT findings.

Clinicopathologic analysis of 19 cases of usual type vulvar intraepithelial neoplasia / 中华妇产科杂志

Objective To reclassify the patients with former diagnosis of vulvar intraepithelial neoplasia (VIN)Ⅱ, VIN Ⅱ - Ⅲ, VIN Ⅲ, Bowen disease and Bowenoid papulosis according to the 2004 modified terminology of International Society for the Study of Vulvar Disease (ISSVD) and evaluate the effects of surgical treatment. Methods According to the 2004 modified terminology of ISSVD, a retrospective review of the histological slides of 19 cases, who diagnosed as VIN Ⅱ , VIN Ⅱ - Ⅲ, VIN Ⅲ,Bowen disease and Bowenoid papulosis treated in Peking Union Medical College Hospital from 1999 to 2006,were performed to reclassify by pathologist and the clinicopathologic data were also analyze& Results According to the 2004 modified terminology of ISSVD, all 19 cases were reclassified as usual type VIN and were belonged to the subtype of warty type except one, the only Bowen disease patient whose one of focuses belonged to the subtype of basaloid type and the other focus belonged to the subtype of warty type. The primary cure rate of extended local excision was 89% (17/19). There were two cases recurred during follow-up period, and were cured by second surgical treatment and the focuses of recurrence site were still diagnosed as warty type VIN. Conclusions The patients with former diagnosis of VIN Ⅱ , VIN Ⅱ-Ⅲ, VINⅢ, Bowen disease and Bowenoid papulosis are basically reclassified as usual type VIN (warty type) according to the 2004 modified terminology of ISSVD. The results showed that the diagnosis of VIN could be simplified by new terminology. The surgical excision is the good choice and combined cytologic and human papillomavims (HPV) test during follow up is also important for patients of VIN.

Clinical features of Gorham-Stout syndrome and literature review / 中华内科杂志

Objective To describe the clinical presentations,radiographic findings and histological pathology of bones,diagnosis,treatment options and prognosis for patients with Gorham-Stout syndrome (GSS).Methods Clinical data of 5 GSS patients seen from January 1980 to January 2008 were reviewed.Results(1)There were 2 males and 3 females,aged 15 years to 37 years(mean age was 30.2 years).(2)All of thern had osteolysis,but the site and extent of involved bones were not the same.Three cases had large amount of bloody pieural effusion and two of them had also chylous effusion.All of the 5 cases had no evidence of malignancies.Four cases accepted bone biopsy.Among them,2 cases having local puncture and open biopsy showed typical bone pathologic manifestations.(3)Various forms of treatment including bisphosphonates,calcium supplementation,active vitD3 treatment,local radiation therapy and surgical ligation of thoracic duct were tried.(4)Follow up and clinical outcomes:the two cases,who had only bone osteolysis remained stable.Of the other three cases who had bone osteolysis associated with pleural effusion,one patient needed interrupted effusion drainage with stable bone impairment and the other two cases were out of contact.Conclusions GSS is a rare disorder charactcrized by progressive osteoIysis.The clinical presentations of this disease are variable and depend on the sites of involvement.There were no standard therapy available.Prognosis depends on the site of involvement,extent of the disease and presence of complications.Those who have plueral effusion had poor prognosis.

Nervous system relapse in primary plasma cell leukemia / 基础医学与临床

Objective To improve the anderstanding of clinical profile of primary plasma cell leukemia.Methods Case report and literature review.Results A rare case of nervous system relapse in primary plasma cell leukemia was reported.Six patients were identified from the literature.The type of immunoglobulin included IgG(3 patients),IgD(2 patients).Clinical manifestations of nervous system were variable.The average interval from initial diagnosis to the development of nervous system relapse was 16.5 months.Plasma cells were found in cerebrospinal fluid in 4 patients.The mean surviaval time was 6.7 months after nervous system relapse.Conlusion Nervous system relapse in primary plasma cell leukemia is rare with poor prognosis.